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Dorent R, Guihaire J, Kerforne T, Abdoul-Anziz N, Goeminne C, Provenchere S, Lepoivre T, Nesseler N, Pontailler M, Flecher E, Venhard JC, Schloesing C, Santin G, Legeai C, Tsimaratos M, Lebreton G, Coutance G, Kerbaul F. Donation after circulatory death heart transplantation: The French perspective. Arch Cardiovasc Dis 2025; 118:405-412. [PMID: 40246654 DOI: 10.1016/j.acvd.2025.03.120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 04/19/2025]
Abstract
Heart transplantation is the gold standard treatment for patients with advanced heart failure in the absence of contraindications. In recent years, the shortage of heart donors has led to a resurgence in the use of hearts from donation after circulatory death (DCD) donors after withdrawal of life-sustaining treatment. In these donors, death is determined by the cessation of spontaneous circulation and respiration for≥5minutes and is confirmed by neurological criteria. Two heart procurement procedures are used, namely direct procurement and perfusion (DPP) and procurement after thoracoabdominal-normothermic regional perfusion (TA-NRP). Donor hearts procured using TA-NRP are reperfused and assessed inside the donor and preserved with static cold storage or ex situ machine perfusion. With DPP, hearts are reperfused and assessed ex situ with a perfusion machine. The ischaemic time before heart reperfusion is shorter with TA-NRP than with direct procurement followed by ex situ perfusion. The TA-NRP technique allows for the assessment of the function of the donor heart. Numerous studies have reported similar survival rates between recipients who have received hearts from DCD and donation after brain death (DBD) donors. The incidence of severe primary graft dysfunction varies according to the team's learning curve and the country. The heart utilization rate is greater with TA-NRP procurement than DPP. This article describes the two donor heart procurement techniques, provides a summary of the relevant literature on the outcomes of transplantation from DCD donors and reports the position of a working group, convened by the French national transplant agency, on donor and recipient selection.
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Affiliation(s)
- Richard Dorent
- Agence de la biomédecine, direction prélèvement greffe organes-tissus, 93212 Saint-Denis La Plaine, France.
| | - Julien Guihaire
- Département de chirurgie cardiaque, hôpital Marie-Lannelongue, groupe hospitalier Paris Saint-Joseph, 92350 Le Plessis-Robinson, France
| | - Thomas Kerforne
- Département d'anesthésie-réanimation, centre hospitalier universitaire de Poitiers, 86000 Poitiers, France
| | - Naissa Abdoul-Anziz
- Agence de la biomédecine, direction prélèvement greffe organes-tissus, 93212 Saint-Denis La Plaine, France
| | - Céline Goeminne
- Service de cardiologie, hôpital cardiologique, centre hospitalier régional et universitaire de Lille, 59000 Lille, France
| | - Sophie Provenchere
- Département d'anesthésie-réanimation, hôpital Bichat, Assistance publique-Hôpitaux de Paris, 75018 Paris, France
| | - Thierry Lepoivre
- Département d'anesthésie-réanimation, hôpital Hotel-Dieu, centre hospitalier universitaire de Nantes, 44000 Nantes, France
| | - Nicolas Nesseler
- Département d'anesthésie-réanimation, hôpital Pontchaillou, centre hospitalier universitaire de Rennes, 35000 Rennes, France
| | - Margaux Pontailler
- Service de chirurgie cardiaque, hôpital Necker, Assistance publique-Hôpitaux de Paris, 75015 Paris, France
| | - Erwan Flecher
- Service de chirurgie cardiaque, hôpital Pontchaillou, centre hospitalier universitaire de Rennes, 35000 Rennes, France
| | - Jean-Christophe Venhard
- Pôle anesthésie-réanimation, coordination hospitalière des prélèvements d'organes et de tissus, hôpital Trousseau, centre hospitalier régional et universitaire de Tours, 37000 Tours, France
| | - Cyril Schloesing
- Coordination hospitalière des prélèvements d'organes et de tissus, hôpital Bicêtre, Assistance publique-Hôpitaux de Paris, 94270 Kremlin-Bicêtre, France
| | - Gaelle Santin
- Agence de la biomédecine, direction prélèvement greffe organes-tissus, 93212 Saint-Denis La Plaine, France
| | - Camille Legeai
- Agence de la biomédecine, direction prélèvement greffe organes-tissus, 93212 Saint-Denis La Plaine, France
| | - Michel Tsimaratos
- Agence de la biomédecine, direction prélèvement greffe organes-tissus, 93212 Saint-Denis La Plaine, France
| | - Guillaume Lebreton
- Service de chirurgie cardiovasculaire, hôpital Pitié-Salpêtrière, Assistance publique-Hôpitaux de Paris, 75013 Paris, France
| | - Guillaume Coutance
- Service de chirurgie cardiovasculaire, hôpital Pitié-Salpêtrière, Assistance publique-Hôpitaux de Paris, 75013 Paris, France
| | - François Kerbaul
- Agence de la biomédecine, direction prélèvement greffe organes-tissus, 93212 Saint-Denis La Plaine, France
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Hessheimer AJ, Hartog H, Marcon F, Schlegel A, Adam R, Alwayn I, Angelico R, Antoine C, Berlakovich G, Bruggenwirth I, Calatayud D, Cardini B, Cillo U, Clavien PA, Czigany Z, De Carlis R, de Jonge J, De Meijer VE, Dondossola D, Domínguez-Gil B, Dutkowski P, Eden J, Eshmuminov D, Fundora Y, Gastaca M, Ghinolfi D, Justo I, Lesurtel M, Leuvenink H, Line PD, Lladó L, López López V, Lurje G, Marín LM, Monbaliu D, Muller X, Nadalin S, Nasralla D, Oniscu G, Patrono D, Pirenne J, Selzner M, Toso C, Troisi R, Van Beekum C, Watson C, Weissenbacher A, Zieniewicz K, Schneeberger S, Polak WG, Porte RJ, Fondevila C. Deceased donor liver utilisation and assessment: Consensus guidelines from the European Liver and Intestine Transplant Association. J Hepatol 2025; 82:1089-1109. [PMID: 40189968 DOI: 10.1016/j.jhep.2025.01.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 01/11/2025] [Accepted: 01/23/2025] [Indexed: 05/03/2025]
Abstract
Over the past two decades, the application of machine perfusion (MP) in human liver transplantation has moved from the realm of clinical exploration to routine clinical practice. Both in situ and ex situ perfusion strategies are feasible, safe, and may offer improvements in relevant post-transplant outcomes. An important utility of these strategies is the ability to transplant grafts traditionally considered too risky to transplant using conventional cold storage alone. While dynamic assessment and ultimately transplantation of such livers is an important goal for the international liver transplant community, its clinical application is inconsistent. To this end, ELITA (the European Liver and Intestine Transplant Association) gathered a panel of experts to create consensus guidelines regarding selection, approach, and criteria for deceased donor liver assessment in the MP era. An eight-member steering committee (SC) convened a panel of 44 professionals working in 14 countries in Europe and North America. The SC identified topics related to liver utilisation and assessment for transplantation. For each topic, subtopics were created to answer specific clinical questions. A systematic literature review was performed, and the panel graded relevant evidence. The SC drafted initial statements addressing each clinical question. Statements were presented at the in-person Consensus Meeting on Liver Discard and Viability Assessment during the ELITA Summit held from April 19-20, 2024, in Madrid, Spain. Online voting was held to approve statements according to a modified Delphi method; statements reaching ≥85% agreement were approved. Statements addressing liver utilisation, the definition of high-risk livers, and strategies and criteria for dynamic liver assessment are presented.
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Affiliation(s)
- Amelia J Hessheimer
- General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
| | - Hermien Hartog
- University of Groningen & University Medical Center Groningen, UMCG Comprehensive Transplant Center, Department of Surgery, Groningen, the Netherlands; European Liver & Intestine Transplant Association Board
| | - Francesca Marcon
- General & Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Andrea Schlegel
- Transplantation Center, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - René Adam
- Department of Hepatobiliary Surgery & Transplantation, AP-HP Hôpital Paul-Brousse, University of Paris-Saclay, Villejuif, France
| | - Ian Alwayn
- Department of Surgery & LUMC Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
| | - Roberta Angelico
- Hepatobiliary & Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | | | | | | | - David Calatayud
- Hepatobiliary Surgery & Transplantation Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Benno Cardini
- Department of Visceral, Transplant, & Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Umberto Cillo
- Department of Surgery, Oncology, & Gastroenterology, Hepatobiliary & Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Pierre-Alain Clavien
- Wyss Translational Center, ETH Zurich & University of Zurich, Zurich, Switzerland
| | - Zoltan Czigany
- Department of Surgery & Transplantation, University Hospital Heidelberg, Medical Faculty Ruprecht Karl University Heidelberg, Heidelberg, Germany
| | - Riccardo De Carlis
- Department of General Surgery & Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, & PhD Course in Clinical and Experimental Sciences, University of Padua, Padua, Italy
| | - Jeroen de Jonge
- Division of HPB & Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Vincent E De Meijer
- University of Groningen & University Medical Center Groningen, UMCG Comprehensive Transplant Center, Department of Surgery, Groningen, the Netherlands
| | - Daniele Dondossola
- General & Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Philipp Dutkowski
- Department of Visceral Surgery, University Hospital Basel, Basel, Switzerland
| | - Janina Eden
- University of Groningen & University Medical Center Groningen, UMCG Comprehensive Transplant Center, Department of Surgery, Groningen, the Netherlands
| | - Dilmurodjon Eshmuminov
- Department of Surgery & Transplantation, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Yiliam Fundora
- General & Digestive Surgery Service, Hospital Clínic, Barcelona, Spain
| | - Mikel Gastaca
- Hepatobiliary Surgery & Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Bilbao, Spain
| | - Davide Ghinolfi
- Division of Hepatic Surgery & Liver Transplantation, New Santa Chiara Hospital, Pisa, Italy
| | | | - Mickael Lesurtel
- Department of HPB & Transplantation, Beaujon Hospital, APHP, University of Paris Cité, Paris, France
| | - Henri Leuvenink
- University of Groningen & University Medical Center Groningen, UMCG Comprehensive Transplant Center, Department of Surgery, Groningen, the Netherlands
| | - Pal-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; European Liver & Intestine Transplant Association Board
| | - Laura Lladó
- Department of Hepatobiliary Surgery & Liver Transplantation, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Víctor López López
- Department of Surgery & Transplantation, Hospital Clínico Universitario Virgen de la Arrixaca, Murcian Institute of Biosanitary Research, Murcia, Spain
| | - Georg Lurje
- Department of Surgery & Transplantation, University Hospital Heidelberg, Medical Faculty Ruprecht Karl University Heidelberg, Heidelberg, Germany
| | | | | | - Xavier Muller
- Department of Hepato-Pancreato-Biliary Surgery & Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Silvio Nadalin
- University of Tübingen, Tübingen, Germany; European Liver & Intestine Transplant Association Board
| | - David Nasralla
- Department of HPB and Liver Transplant Surgery, Royal Free Hospital, London, United Kingdom
| | - Gabriel Oniscu
- Transplantation Division, Department of Clinical Science, Intervention, & Technology, Karolinska Institutet, Stockholm, Sweden
| | - Damiano Patrono
- General Surgery 2U - Liver Transplant Centre, AOU Città della Salute e della Scienza di Torino, Torino, Italy
| | - Jacques Pirenne
- Abdominal Transplant Surgery, UZ Leuven, KUL, Leuven, Belgium
| | - Markus Selzner
- Department of Abdominal Transplant & Hepatopancreatobiliary Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Christian Toso
- Division of Abdominal Surgery, Geneva University Hospitals, Geneva, Switzerland
| | - Roberto Troisi
- Division HPB, Minimally Invasive and Robotic Surgery, Transplantation Center, Federico II University Hospital, Naples, Italy
| | - Cornelius Van Beekum
- Department of General, Visceral, & Transplant Surgery, Transplant Center Hannover, Hannover Medical School, Hannover, Germany
| | - Christopher Watson
- University of Cambridge Department of Surgery, Addenbrookes Hospital, Cambridge, United Kingdom
| | - Annemarie Weissenbacher
- Department of Visceral, Transplant, & Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Krzysztof Zieniewicz
- Department of General, Transplant, & Liver Surgery, Medical University of Warsaw, Warsaw, Poland; European Liver & Intestine Transplant Association Board
| | - Stefan Schneeberger
- Department of Visceral, Transplant, & Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Wojciech G Polak
- Division of HPB & Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands; European Liver & Intestine Transplant Association Board
| | - Robert J Porte
- Division of HPB & Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Constantino Fondevila
- General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain; Universidad Autónoma de Madrid, Madrid, Spain; European Liver & Intestine Transplant Association Board.
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Stahl CC, Aufhauser DD. Normothermic regional perfusion and liver transplant: expanding the donation after circulatory death donor pool. Curr Opin Organ Transplant 2025:00075200-990000000-00183. [PMID: 40366020 DOI: 10.1097/mot.0000000000001230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
PURPOSE OF REVIEW Normothermic regional perfusion (NRP) is a novel technique developed to improve organ utilization and recipient outcomes following donation after circulatory death (DCD). NRP has revolutionized DCD liver transplant by extending donor criteria and reducing the incidence of ischemic cholangiopathy (IC) and other complications in recipients. However, there is significant geographic and center-specific variation in NRP use and practices. This review collates practices from pioneering NRP centers across the globe regarding donor selection criteria, NRP techniques, organ viability monitoring, and other key areas to help guide the continued growth of NRP liver transplantation. RECENT FINDINGS DCD livers recovered using NRP have consistently demonstrated excellent outcomes, with IC and patient and graft survival rates approaching those seen with grafts from donation after brain death donors. Recently, transplant centers have been working to increase the DCD donor pool by relaxing limits on donor quality, reconsidering organ viability markers, and combining NRP with ex situ machine perfusion technologies. SUMMARY NRP is a powerful organ recovery technology transforming the practice of DCD liver transplantation. Current evidence suggests that organ utilization could be further expanded using NRP recovery, with excellent clinical outcomes reported by centers using less stringent donor and organ viability criteria.
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Gastaca M, Ruiz P, Bustamante J, Ventoso A. Letter to the Editor: Normothermic regional perfusion in controlled DCD liver procurement: Comparable outcomes to DBD liver transplantation in 3 different European countries. Liver Transpl 2025; 31:E18-E19. [PMID: 39679921 DOI: 10.1097/lvt.0000000000000555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 12/17/2024]
Affiliation(s)
- Mikel Gastaca
- Liver Transplantation Unit, BioBizkaia Health Research Institute, Cruces University Hospital, University of the Basque Country, Baracaldo, Vizcaya, Spain
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Royo-Villanova M, Miñambres E, Coll E, Domínguez-Gil B. Normothermic Regional Perfusion in Controlled Donation After the Circulatory Determination of Death: Understanding Where the Benefit Lies. Transplantation 2025; 109:428-439. [PMID: 39049104 DOI: 10.1097/tp.0000000000005143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
Controlled donation after the circulatory determination of death (cDCDD) has emerged as a strategy to increase the availability of organs for clinical use. Traditionally, organs from cDCDD donors have been subject to standard rapid recovery (SRR) with poor posttransplant outcomes of abdominal organs, particularly the liver, and limited organ utilization. Normothermic regional perfusion (NRP), based on the use of extracorporeal membrane oxygenation devices, consists of the in situ perfusion of organs that will be subject to transplantation with oxygenated blood under normothermic conditions after the declaration of death and before organ recovery. NRP is a potential solution to address the limitations of traditional recovery methods. It has become normal practice in several European countries and has been recently introduced in the United States. The increased use of NRP in cDCDD has occurred as a result of a growing body of evidence on its association with improved posttransplant outcomes and organ utilization compared with SRR. However, the expansion of NRP is precluded by obstacles of an organizational, legal, and ethical nature. This article details the technique of both abdominal and thoracoabdominal NRP. Based on the available evidence, it describes its benefits in terms of posttransplant outcomes of abdominal and thoracic organs and organ utilization. It addresses cost-effectiveness aspects of NRP, as well as logistical and ethical obstacles that limit the implementation of this innovative preservation strategy.
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Affiliation(s)
- Mario Royo-Villanova
- Transplant Coordination Unit and Service of Intensive Care, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Eduardo Miñambres
- Transplant Coordination Unit and Service of Intensive Care, University Hospital Marqués de Valdecilla-IDIVAL, School of Medicine, Universidad de Cantabria, Santander, Spain
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Otajonova N, Martinez EJ, Gupta A, Bayer J, Testa G, Wall AE. Liver transplant program utilization of donation after circulatory death liver grafts by procurement technique and storage modality: a survey of US liver transplant surgical directors. Proc AMIA Symp 2025; 38:253-258. [PMID: 40291102 PMCID: PMC12026106 DOI: 10.1080/08998280.2025.2457899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 01/15/2025] [Accepted: 01/20/2025] [Indexed: 04/30/2025] Open
Abstract
Introduction Donation after circulatory death (DCD) increased in the US over the past decade. However, 30% of DCD liver grafts procured for transplantation are not utilized. Barriers to DCD liver utilization include quality concerns, particularly the risk of ischemic cholangiopathy and retransplantation, and costs associated with DCD organ acquisition. This study investigated the attitudes of the liver transplantation community in the US toward DCD and identified barriers to DCD liver utilization. Methods RedCap survey of liver transplantation surgical directors in the US. Results Of 101 liver transplantation surgical directors, 24 responded to the survey, and 96% of respondents accepted DCD donors. Most programs accepted livers from thoracoabdominal normothermic regional perfusion with cold storage (96%), while substantially fewer accepted liver grafts from rapid recovery DCD donors with cold storage (67%). Sixty-five percent of transplant centers' functional warm ischemic time started when oxygen saturation or systolic blood pressure was <80%/mm Hg; 13% started at extubation, 17.4% started at systolic blood pressure <80 mm Hg, and 4.3% used a systolic blood pressure <50 mm Hg. Conclusion We found variability among transplant programs in DCD liver graft acceptance based on procuring surgeon, procurement technique, and storage modality. Quality and cost are two main barriers to DCD liver utilization, with the main tradeoffs being between rapid recovery with static cold storage (lower cost, lower quality) and machine perfusion/normothermic regional perfusion (higher cost, better quality).
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Affiliation(s)
- Nazokat Otajonova
- Department of General Surgery, Yale New Haven Health, New Haven, Connecticut, USA
| | - Eric J. Martinez
- Annette C. and Harold C. Simmons Transplant Institute, Abdominal Transplant, Baylor Scott & White Health, Dallas, Texas, USA
| | - Amar Gupta
- Annette C. and Harold C. Simmons Transplant Institute, Abdominal Transplant, Baylor Scott & White Health, Dallas, Texas, USA
| | - Johanna Bayer
- Annette C. and Harold C. Simmons Transplant Institute, Abdominal Transplant, Baylor Scott & White Health, Dallas, Texas, USA
| | - Giuliano Testa
- Annette C. and Harold C. Simmons Transplant Institute, Abdominal Transplant, Baylor Scott & White Health, Dallas, Texas, USA
| | - Anji E. Wall
- Annette C. and Harold C. Simmons Transplant Institute, Abdominal Transplant, Baylor Scott & White Health, Dallas, Texas, USA
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Vidgren M, Delorme C, Oniscu GC. Challenges and opportunities in organ donation after circulatory death. J Intern Med 2025; 297:124-140. [PMID: 39829342 PMCID: PMC11771584 DOI: 10.1111/joim.20051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
In recent years, there has been resurgence in donation after circulatory death (DCD). Despite that, the number of organs transplanted from these donors remains low due to concerns about their function and a lack of an objective assessment at the time of donation. This overview examines the current DCD practices and the classification modifications to accommodate regional perspectives. Several risk factors underscore the reluctance to accept DCD organs, and we discuss the modern strategies to mitigate them. The advent of machine perfusion technology has revolutionized the field of DCD transplantation, leading to improved outcomes and better organ usage. With many strategies at our disposal, there is an urgent need for comparative trials to determine the optimal use of perfusion technologies for each donated organ type. Additional progress in defining therapeutic strategies to repair the damage sustained during the dying process should further improve DCD organ utilization and outcomes. However, there remains wide variability in access to DCD donation and transplantation, and organizational efforts should be doubled up with consensus on key ethical issues that still surround DCD donation in the era of machine perfusion.
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Affiliation(s)
- Mathias Vidgren
- Division of Transplantation SurgeryCLINTEC, Karolinska InstitutetStockholmSweden
- Department of Transplantation SurgeryKarolinska Universitetssjukhuset HuddingeHuddingeSweden
| | - Capucine Delorme
- Division of Transplantation SurgeryCLINTEC, Karolinska InstitutetStockholmSweden
- Department of Transplantation SurgeryKarolinska Universitetssjukhuset HuddingeHuddingeSweden
| | - Gabriel C. Oniscu
- Division of Transplantation SurgeryCLINTEC, Karolinska InstitutetStockholmSweden
- Department of Transplantation SurgeryKarolinska Universitetssjukhuset HuddingeHuddingeSweden
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Eyraud D, Philippe A, Guerin C, Sarmiento I, Suner L, Puybasset L, Bertil S, Vaillant JC, Helley D, Granger B, Smadja DM, Gaussem P. Cirrhotic Patients Exhibit Remarkable Vascular Regenerative Profile One Month after Liver Transplantation. Stem Cell Rev Rep 2025; 21:276-279. [PMID: 39377987 DOI: 10.1007/s12015-024-10796-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2024] [Indexed: 01/26/2025]
Affiliation(s)
- Daniel Eyraud
- Université Pierre et Marie Curie, Paris, France, Department of Anesthesiology and Reanimation, AP-HP, Pitié-Salpêtrière University Hospital, Paris, F-75013, France
| | - Aurélien Philippe
- Service d'hématologie biologique, AP-HP, Université de Paris Cité, Hôpital Européen Georges Pompidou, Paris, F-75015, France
- Université de Paris Cité, Innovative Therapies in Haemostasis, INSERM, Paris, F-75006, France
| | - Coralie Guerin
- Université de Paris Cité, Innovative Therapies in Haemostasis, INSERM, Paris, F-75006, France
- Cytometry Platform, Curie CoreTech, Institut Curie, Paris, F-75005, France
| | - Ignacio Sarmiento
- Université Pierre et Marie Curie, Paris, France, Department of Anesthesiology and Reanimation, AP-HP, Pitié-Salpêtrière University Hospital, Paris, F-75013, France
| | - Ludovic Suner
- Service d'hématologie biologique, AP-HP, Université de Paris Cité, Hôpital Européen Georges Pompidou, Paris, F-75015, France
| | - Louis Puybasset
- Université Pierre et Marie Curie, Paris, France, Department of Anesthesiology and Reanimation, AP-HP, Pitié-Salpêtrière University Hospital, Paris, F-75013, France
| | - Sébastien Bertil
- Service d'hématologie biologique, AP-HP, Université de Paris Cité, Hôpital Européen Georges Pompidou, Paris, F-75015, France
| | - Jean-Christophe Vaillant
- Université Pierre et Marie Curie, Paris, France, Department of Digestive, HPB Surgery, and Liver Transplantation, AP-HP, Pitié-Salpêtrière University Hospital, Paris, F-75013, France
| | - Dominique Helley
- Service d'hématologie biologique, AP-HP, Université de Paris Cité, Hôpital Européen Georges Pompidou, Paris, F-75015, France
- Université de Paris Cité, Paris Cardiovascular Research Center, Paris, F-75015, France
| | - Benjamin Granger
- Université Pierre et Marie Curie, Paris, France, Department of statistics, Clinical Research Unit, AP-HP, Pitié-Salpêtrière University Hospital, Paris, F-75013, France
| | - David M Smadja
- Service d'hématologie biologique, AP-HP, Université de Paris Cité, Hôpital Européen Georges Pompidou, Paris, F-75015, France.
- Université de Paris Cité, Innovative Therapies in Haemostasis, INSERM, Paris, F-75006, France.
| | - Pascale Gaussem
- Service d'hématologie biologique, AP-HP, Université de Paris Cité, Hôpital Européen Georges Pompidou, Paris, F-75015, France
- Université de Paris Cité, Innovative Therapies in Haemostasis, INSERM, Paris, F-75006, France
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Cywes C, Banker A, Muñoz N, Levine M, Abu-Gazala S, Bittermann T, Abt P. The Potential Utilization of Machine Perfusion to Increase Transplantation of Macrosteatotic Livers. Transplantation 2024; 108:e370-e375. [PMID: 38773856 DOI: 10.1097/tp.0000000000005057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2024]
Abstract
BACKGROUND The demand for liver transplantation has led to the utilization of marginal grafts including moderately macrosteatotic livers (macrosteatosis ≥30% [Mas30]), which are associated with an elevated risk of graft failure. Machine perfusion (MP) has emerged as a technique for organ preservation and viability testing; however, little is known about MP in Mas30 livers. This study evaluates the utilization and outcomes of Mas30 livers in the era of MP. METHODS The Organ Procurement and Transplantation Network database was queried to identify biopsy-proven Mas30 deceased donor liver grafts between June 1, 2016, and June 23, 2023. Univariable and multivariable models were constructed to study the association between MP and graft utilization and survival. RESULTS The final cohort with 3317 Mas30 livers was identified, of which 72 underwent MP and were compared with 3245 non-MP livers. Among Mas30 livers, 62 (MP) and 1832 (non-MP) were transplanted (utilization of 86.1% versus 56.4%, P < 0.001). Donor and recipient characteristics were comparable between MP and non-MP groups. In adjusted analyses, MP was associated with significantly increased Mas30 graft utilization (odds ratio, 7.89; 95% confidence interval [CI], 3.76-16.58; P < 0.001). In log-rank tests, MP was not associated with 1- and 3-y graft failure (hazard ratio, 0.49; 95% CI, 0.12-1.99; P = 0.319 and hazard ratio 0.43; 95% CI, 0.11-1.73; P = 0.235, respectively). CONCLUSIONS The utilization rate of Mas30 grafts increases with MP without detriment to graft survival. This early experience may have implications for increasing the available donor pool of Mas30 livers.
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Affiliation(s)
- Claire Cywes
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Amay Banker
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Nicolas Muñoz
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Matthew Levine
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Samir Abu-Gazala
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Therese Bittermann
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Peter Abt
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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10
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Malik AK, Tingle SJ, Varghese C, Owen R, Mahendran B, Figueiredo R, Amer AO, Currie IS, White SA, Manas DM, Wilson CH. Does Time to Asystole in Donors After Circulatory Death Impact Recipient Outcome in Liver Transplantation? Transplantation 2024; 108:2238-2246. [PMID: 38780399 PMCID: PMC11495538 DOI: 10.1097/tp.0000000000005074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 03/06/2024] [Accepted: 04/04/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND The agonal phase can vary following treatment withdrawal in donor after circulatory death (DCD). There is little evidence to support when procurement teams should stand down in relation to donor time to death (TTD). We assessed what impact TTD had on outcomes following DCD liver transplantation. METHODS Data were extracted from the UK Transplant Registry on DCD liver transplant recipients from 2006 to 2021. TTD was the time from withdrawal of life-sustaining treatment to asystole, and functional warm ischemia time was the time from donor systolic blood pressure and/or oxygen saturation falling below 50 mm Hg and 70%, respectively, to aortic perfusion. The primary endpoint was 1-y graft survival. Potential predictors were fitted into Cox proportional hazards models. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. RESULTS One thousand five hundred fifty-eight recipients of a DCD liver graft were included. Median TTD in the entire cohort was 13 min (interquartile range, 9-17 min). Restricted cubic splines revealed that the risk of graft loss was significantly greater when TTD ≤14 min. After 14 min, there was no impact on graft loss. Prolonged hepatectomy time was significantly associated with graft loss (hazard ratio, 1.87; 95% confidence interval, 1.23-2.83; P = 0.003); however, functional warm ischemia time had no impact (hazard ratio, 1.00; 95% confidence interval, 0.44-2.27; P > 0.9). CONCLUSIONS A very short TTD was associated with increased risk of graft loss, possibly because of such donors being more unstable and/or experiencing brain stem death as well as circulatory death. Expanding the stand down times may increase the utilization of donor livers without significantly impairing graft outcome.
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Affiliation(s)
- Abdullah K. Malik
- Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Samuel J. Tingle
- Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Chris Varghese
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Ruth Owen
- Department of Surgery, The Royal Oldham Hospital, Greater Manchester, United Kingdom
| | - Balaji Mahendran
- Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Rodrigo Figueiredo
- Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Aimen O. Amer
- Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Ian S. Currie
- National Health Service Blood and Transplant, Bristol, United Kingdom
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Steven A. White
- Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Derek M. Manas
- Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Newcastle University, Newcastle upon Tyne, United Kingdom
- National Health Service Blood and Transplant, Bristol, United Kingdom
| | - Colin H. Wilson
- Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Newcastle University, Newcastle upon Tyne, United Kingdom
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11
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Parente A, Kasahara M, De Meijer VE, Hashimoto K, Schlegel A. Efficiency of machine perfusion in pediatric liver transplantation. Liver Transpl 2024; 30:1188-1199. [PMID: 38619390 PMCID: PMC11472901 DOI: 10.1097/lvt.0000000000000381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 03/27/2024] [Indexed: 04/16/2024]
Abstract
Liver transplantation is the only life-saving procedure for children with end-stage liver disease. The field is however heterogenic with various graft types, recipient age, weight, and underlying diseases. Despite recently improved overall outcomes and the expanded use of living donors, waiting list mortality remains unacceptable, particularly in small children and infants. Based on the known negative effects of elevated donor age, higher body mass index, and prolonged cold ischemia time, the number of available donors for pediatric recipients is limited. Machine perfusion has regained significant interest in the adult liver transplant population during the last decade. Ten randomized controlled trials are published with an overall advantage of machine perfusion techniques over cold storage regarding postoperative outcomes, including graft survival. The concept of hypothermic oxygenated perfusion (HOPE) was the first and only perfusion technique used for pediatric liver transplantation today. In 2018 the first pediatric candidate received a full-size graft donated after circulatory death with cold storage and HOPE, followed by a few split liver transplants after HOPE with an overall limited case number until today. One series of split procedures during HOPE was recently presented by colleagues from France with excellent results, reduced complications, and better graft survival. Such early experience paves the way for more systematic use of machine perfusion techniques for different graft types for pediatric recipients. Clinical reports of pediatric liver transplants with other perfusion techniques are awaited. Strong collaborative efforts are needed to explore the effect of perfusion techniques in this vulnerable population impacting not only the immediate posttransplant outcome but the development and success of an entire life.
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Affiliation(s)
- Alessandro Parente
- Department of Surgery, Division of Transplantation, University of Alberta, Edmonton, Alberta, Canada
- HPB and Transplant Unit, Department of Surgical Science, University of Rome Tor Vergata, Rome, Italy
| | - Mureo Kasahara
- Department of Surgery, Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Vincent E. De Meijer
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Koji Hashimoto
- Department of Surgery, Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Andrea Schlegel
- Department of Surgery, Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
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12
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Mastrovangelis C, Frost C, Hort A, Laurence J, Pang T, Pleass H. Normothermic Regional Perfusion in Controlled Donation After Circulatory Death Liver Transplantation: A Systematic Review and Meta-Analysis. Transpl Int 2024; 37:13263. [PMID: 39246548 PMCID: PMC11377255 DOI: 10.3389/ti.2024.13263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 08/13/2024] [Indexed: 09/10/2024]
Abstract
Liver grafts from controlled donation after circulatory death (cDCD) donors have lower utilization rates due to inferior graft and patient survival rates, largely attributable to the increased incidence of ischemic cholangiopathy, when compared with grafts from brain dead donors (DBD). Normothermic regional perfusion (NRP) may improve the quality of cDCD livers to allow for expansion of the donor pool, helping to alleviate the shortage of transplantable grafts. A systematic review and metanalysis was conducted comparing NRP cDCD livers with both non-NRP cDCD livers and DBD livers. In comparison to non-NRP cDCD outcomes, NRP cDCD grafts had lower rates of ischemic cholangiopathy [RR = 0.23, 95% CI (0.11, 0.49), p = 0.0002], primary non-function [RR = 0.51, 95% CI (0.27, 0.97), p = 0.04], and recipient death [HR = 0.5, 95% CI (0.36, 0.69), p < 0.0001]. There was no difference in outcomes between NRP cDCD donation compared to DBD liver donation. In conclusion, NRP improved the quality of cDCD livers compared to their non-NRP counterparts. NRP cDCD livers had similar outcomes to DBD grafts. This provides further evidence supporting the continued use of NRP in cDCD liver transplantation and offers weight to proposals for its more widespread adoption.
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Affiliation(s)
- Carly Mastrovangelis
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Charles Frost
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Amy Hort
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
| | - Jerome Laurence
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
- Department of Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Tony Pang
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
- Surgical Innovations Unit, Westmead Hospital, Westmead, NSW, Australia
| | - Henry Pleass
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
- Department of Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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13
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Prudhomme T, Mesnard B, Branchereau J, Roumiguié M, Maulat C, Muscari F, Kamar N, Soulié M, Gamé X, Sallusto F, Timsit MO, Drouin S. Simultaneous liver-kidney transplantation: future perspective. World J Urol 2024; 42:489. [PMID: 39162870 PMCID: PMC11335780 DOI: 10.1007/s00345-024-05174-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 07/11/2024] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND The aims of this narrative review were (i) to describe the current indications of SLKT, (ii) to report evolution of SLKT activity, (iii) to report the outcomes of SLKT, (iv) to explain the immune-protective effect of liver transplant on kidney transplant, (v) to explain the interest of delay kidney transplantation, using hypothermic machine perfusion (HMP), (vi) to report kidney after liver transplantation (KALT) indications and (vii) to describe the value of the increase in the use of extended criteria donors (ECD) and particular controlled donation after circulatory death (cDCD) transplant, thanks to the development of new organ preservation strategies. METHOD Electronic databases were screened using the keywords "Simultaneous", "Combined", "kidney transplantation" and "liver transplantation". The methodological and clinical heterogeneity of the included studies meant that meta-analysis was inappropriate. RESULTS A total of 1,917 publications were identified in the literature search. Two reviewers screened all study abstracts independently and 1,107 of these were excluded. Thus, a total of 79 full text articles were assessed for eligibility. Of these, 21 were excluded. In total, 58 studies were included in this systematic review. CONCLUSIONS Simultaneous liver-kidney transplantation has made a significant contribution for patients with dual-organ disease. The optimization of indication and selection of SLKT patients will reduce futile transplantation. Moreover, increasing the use of transplants from extended criteria donors, in particular cDCD, should be encouraged, thanks to the development of new modalities of organ preservation.
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Affiliation(s)
- Thomas Prudhomme
- Department of Urology, Kidney Transplantation and Andrology, TSA 50032 Rangueil Hospital, Toulouse Cedex 9, 31059, France.
- Center for Research in Transplantation and Translational Immunology, Nantes Université, INSERM, UMR 1064, Nantes, 44000, France.
| | - Benoit Mesnard
- Center for Research in Transplantation and Translational Immunology, Nantes Université, INSERM, UMR 1064, Nantes, 44000, France
- Department of Urology, University Hospital of Nantes, Nantes, France
| | - Julien Branchereau
- Center for Research in Transplantation and Translational Immunology, Nantes Université, INSERM, UMR 1064, Nantes, 44000, France
- Department of Urology, University Hospital of Nantes, Nantes, France
| | - Mathieu Roumiguié
- Department of Urology, Kidney Transplantation and Andrology, TSA 50032 Rangueil Hospital, Toulouse Cedex 9, 31059, France
| | - Charlotte Maulat
- Department of Digestive Surgery, University Hospital of Rangueil, Toulouse, France
| | - Fabrice Muscari
- Department of Digestive Surgery, University Hospital of Rangueil, Toulouse, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, University Hospital of Rangueil, Toulouse, France
| | - Michel Soulié
- Department of Urology, Kidney Transplantation and Andrology, TSA 50032 Rangueil Hospital, Toulouse Cedex 9, 31059, France
| | - Xavier Gamé
- Department of Urology, Kidney Transplantation and Andrology, TSA 50032 Rangueil Hospital, Toulouse Cedex 9, 31059, France
| | - Federico Sallusto
- Department of Urology, Kidney Transplantation and Andrology, TSA 50032 Rangueil Hospital, Toulouse Cedex 9, 31059, France
| | - Marc Olivier Timsit
- Department of Urology, Hôpital Européen Georges Pompidou, APHP-Centre, Paris, France
| | - Sarah Drouin
- Service Médico-Chirurgical de Transplantation Rénale, APHP Sorbonne-Université, Hôpital Pitié-Salpêtrière, Paris, Île-de-France, France
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14
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Hessheimer AJ, Flores E, Vengohechea J, Fondevila C. Better liver transplant outcomes by donor interventions? Curr Opin Organ Transplant 2024; 29:219-227. [PMID: 38785132 DOI: 10.1097/mot.0000000000001153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
PURPOSE OF REVIEW Donor risk factors and events surrounding donation impact the quantity and quality of grafts generated to meet liver transplant waitlist demands. Donor interventions represent an opportunity to mitigate injury and risk factors within donors themselves. The purpose of this review is to describe issues to address among donation after brain death, donation after circulatory determination of death, and living donors directly, for the sake of optimizing relevant outcomes among donors and recipients. RECENT FINDINGS Studies on donor management practices and high-level evidence supporting specific interventions are scarce. Nonetheless, for donation after brain death (DBD), critical care principles are employed to correct cardiocirculatory compromise, impaired tissue oxygenation and perfusion, and neurohormonal deficits. As well, certain treatments as well as marginally prolonging duration of brain death among otherwise stable donors may help improve posttransplant outcomes. In donation after circulatory determination of death (DCD), interventions are performed to limit warm ischemia and reverse its adverse effects. Finally, dietary and exercise programs have improved donation outcomes for both standard as well as overweight living donor (LD) candidates, while minimally invasive surgical techniques may offer improved outcomes among LD themselves. SUMMARY Donor interventions represent means to improve liver transplant yield and outcomes of liver donors and grafts.
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Affiliation(s)
- Amelia J Hessheimer
- General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd
| | - Eva Flores
- Transplant Coordination Unit, Hospital Universitario La Paz, Madrid, Spain
| | - Jordi Vengohechea
- General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd
| | - Constantino Fondevila
- General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd
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15
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Brubaker AL, Sellers MT, Abt PL, Croome KP, Merani S, Wall A, Abreu P, Alebrahim M, Baskin R, Bohorquez H, Cannon RM, Cederquist K, Edwards J, Huerter BG, Hobeika MJ, Kautzman L, Langnas AN, Lee DD, Manzi J, Nassar A, Neidlinger N, Nydam TL, Schnickel GT, Siddiqui F, Suah A, Taj R, Taner CB, Testa G, Vianna R, Vyas F, Montenovo MI. US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery. JAMA Surg 2024; 159:677-685. [PMID: 38568597 PMCID: PMC10993160 DOI: 10.1001/jamasurg.2024.0520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 01/06/2024] [Indexed: 04/06/2024]
Abstract
Importance Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.
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Affiliation(s)
- Aleah L. Brubaker
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, University of California San Diego, La Jolla, California
- CONCORD: Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development
| | - Marty T. Sellers
- CONCORD: Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development
- Tennessee Donor Services, Nashville
| | - Peter L. Abt
- CONCORD: Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development
- Department of Surgery, Transplant Division, University of Pennsylvania, Philadelphia
| | - Kristopher P. Croome
- CONCORD: Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development
- Department of Transplant, Mayo Clinic Florida, Jacksonville
| | - Shaheed Merani
- CONCORD: Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development
- Department of Surgery, University of Nebraska Medical Center, Omaha
| | - Anji Wall
- CONCORD: Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas
| | - Phillipe Abreu
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, Florida
| | | | - Roy Baskin
- Methodist Transplant Specialists, Dallas, Texas
| | - Humberto Bohorquez
- Department of Surgery, Ochsner School of Medicine, New Orleans, Louisiana
| | - Robert M. Cannon
- Department of Surgery, University of Alabama at Birmingham, Birmingham
| | - Kelly Cederquist
- Department of Surgery, Transplant Division, University of Pennsylvania, Philadelphia
| | - John Edwards
- Gift of Life Donor Program, Philadelphia, Pennsylvania
| | | | - Mark J. Hobeika
- J.C. Walter Jr Transplant Center, Houston Methodist Hospital, Houston, Texas
| | | | - Alan N. Langnas
- Department of Surgery, University of Nebraska Medical Center, Omaha
| | - David D. Lee
- Department of Surgery, Loyola University, Chicago, Illinois
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Joao Manzi
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, Florida
| | - Ahmed Nassar
- Department of Surgery, Emory University, Atlanta, Georgia
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | | | - Trevor L. Nydam
- CONCORD: Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development
- Department of Surgery, Division of Transplant Surgery, University of Colorado, Aurora
| | - Gabriel T. Schnickel
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, University of California San Diego, La Jolla, California
| | - Farjad Siddiqui
- Department of Surgery, The Ohio State University, Columbus
- Department of Surgery, Emory University, Atlanta, Georgia
| | - Ashley Suah
- Department of Surgery, Emory University, Atlanta, Georgia
- Department of Surgery, University of Chicago, Chicago, Illinois
| | - Raeda Taj
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, University of California San Diego, La Jolla, California
- Department of Surgery, Transplant Division, University of Pennsylvania, Philadelphia
| | | | - Giuliano Testa
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas
| | - Rodrigo Vianna
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, Florida
| | - Frederick Vyas
- Department of Surgery, Transplant Division, University of Pennsylvania, Philadelphia
| | - Martin I. Montenovo
- CONCORD: Consortium for Donation after Circulatory Death and Normothermic Regional Perfusion Outcomes Research and Development
- Department of Surgery, Vanderbilt University, Nashville, Tennessee
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16
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Parente A, Sun K, Dutkowski P, Shapiro AMJ, Schlegel A. Routine utilization of machine perfusion in liver transplantation: Ready for prime time? World J Gastroenterol 2024; 30:1488-1493. [PMID: 38617447 PMCID: PMC11008417 DOI: 10.3748/wjg.v30.i11.1488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 01/30/2024] [Accepted: 02/28/2024] [Indexed: 03/21/2024] Open
Abstract
The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation. Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses, providing the highest available evidence on the protective effect of machine perfusion (MP) over static cold storage in liver transplantation (LT). Based on a protective effect with less complications and improved graft survival, the field has seen a paradigm shift in organ preservation. This editorial focuses on the role of MP in LT and how it could become the new "gold standard". Strong collaborative efforts are needed to explore its effects on long-term outcomes.
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Affiliation(s)
- Alessandro Parente
- Department of Surgery, Division of Transplantation, University of Alberta Hospital, Edmonton T6G 2B7, Canada
| | - Keyue Sun
- Immunity and Inflammation, Lerner Research Institute, Cleveland, OH 44195, United States
| | - Philipp Dutkowski
- Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich 8091, Switzerland
| | - AM James Shapiro
- Department of Surgery, Division of Transplantation, University of Alberta Hospital, Edmonton T6G 2B7, Canada
| | - Andrea Schlegel
- Immunity and Inflammation, Digestive Disease and Surgery Institute, Cleveland, OH 44195, United States
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17
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Motter JD, Jaffe IS, Moazami N, Smith DE, Kon ZN, Piper GL, Sommer PM, Reyentovich A, Chang SH, Aljabban I, Montgomery RA, Segev DL, Massie AB, Lonze BE. Single center utilization and post-transplant outcomes of thoracoabdominal normothermic regional perfusion deceased cardiac donor organs. Clin Transplant 2024; 38:e15269. [PMID: 38445531 DOI: 10.1111/ctr.15269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 01/26/2024] [Accepted: 02/09/2024] [Indexed: 03/07/2024]
Abstract
INTRODUCTION Thoracoabdominal normothermic regional perfusion (TA-NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA-NRP-procured organs are limited by potential misclassification since TA-NRP is not differentiated from donation after cardiac death (DCD) in registry data. METHODS We studied 22 donors whose designees consented to TA-NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe. RESULTS All 22 donors progressed to cardiac arrest and underwent TA-NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA-NRP utilization was high across all organ types (88%-100%), with a higher percentage of kidneys procured via TA-NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA-NRP compared to tDCD donors (27% vs. 44%, p = .045). CONCLUSION Procurement from TA-NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large-scale study of TA-NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.
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Affiliation(s)
- Jennifer D Motter
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
| | - Ian S Jaffe
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
| | - Nader Moazami
- Department of Cardiothoracic Surgery, NYU Grossman School of Medicine, New York, New York, USA
| | - Deane E Smith
- Department of Cardiothoracic Surgery, NYU Grossman School of Medicine, New York, New York, USA
| | - Zachary N Kon
- Department of Cardiothoracic Surgery, North Shore University Hospital, Northwell Health, Manhasset, New York, USA
| | - Greta L Piper
- Department of Cardiothoracic Surgery, North Shore University Hospital, Northwell Health, Manhasset, New York, USA
| | - Philip M Sommer
- Department of Anesthesiology, Perioperative Care, and Pain Medicine, NYU Grossman School of Medicine, New York, New York, USA
| | - Alex Reyentovich
- Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
| | - Stephanie H Chang
- Department of Cardiothoracic Surgery, NYU Grossman School of Medicine, New York, New York, USA
| | - Imad Aljabban
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
- Department of Surgery, Columbia University School of Medicine, New York, New York, USA
| | - Robert A Montgomery
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
| | - Dorry L Segev
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
- Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA
- Scientific Registry of Transplant Recipients, Minneapolis, Minnesota, USA
| | - Allan B Massie
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
- Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA
| | - Bonnie E Lonze
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
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18
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Watson CJ, Gaurav R, Butler AJ. Current Techniques and Indications for Machine Perfusion and Regional Perfusion in Deceased Donor Liver Transplantation. J Clin Exp Hepatol 2024; 14:101309. [PMID: 38274508 PMCID: PMC10806097 DOI: 10.1016/j.jceh.2023.101309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 11/27/2023] [Indexed: 01/27/2024] Open
Abstract
Since the advent of University of Wisconsin preservation solution in the 1980s, clinicians have learned to work within its confines. While affording improved outcomes, considerable limitations still exist and contribute to the large number of livers that go unused each year, often for fear they may never work. The last 10 years have seen the widespread availability of new perfusion modalities which provide an opportunity for assessing organ viability and prolonged organ storage. This review will discuss the role of in situ normothermic regional perfusion for livers donated after circulatory death. It will also describe the different modalities of ex situ perfusion, both normothermic and hypothermic, and discuss how they are thought to work and the opportunities afforded by them.
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Affiliation(s)
- Christopher J.E. Watson
- University of Cambridge Department of Surgery, Box 210, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
- The Roy Calne Transplant Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
| | - Rohit Gaurav
- The Roy Calne Transplant Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
| | - Andrew J. Butler
- University of Cambridge Department of Surgery, Box 210, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
- The Roy Calne Transplant Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
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19
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Longchamp A, Nakamura T, Uygun K, Markmann JF. Role of Machine Perfusion in Liver Transplantation. Surg Clin North Am 2024; 104:45-65. [PMID: 37953040 DOI: 10.1016/j.suc.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Given the current severe shortage of available livers for transplantation, there is an urgent need to maximize the utilization of donor organs. One of the strategies to increase the number of available livers for transplantation is to improve organ utilization through the use of elderly, overweight, or organs donated after circulatory death. However, the utilization of these "marginal" organs was associated with an increased risk of early allograft dysfunction, primary nonfunction, ischemic biliary complications, or even re-transplantation. Ischemia-reperfusion injury is a key mechanism in the pathogenesis of these complications.
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Affiliation(s)
- Alban Longchamp
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Tsukasa Nakamura
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Korkut Uygun
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - James F Markmann
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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20
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Kwon JH, Usry B, Hashmi ZA, Bhandari K, Carnicelli AP, Tedford RJ, Welch BA, Shorbaji K, Kilic A. Donor utilization in heart transplant with donation after circulatory death in the United States. Am J Transplant 2024; 24:70-78. [PMID: 37517554 DOI: 10.1016/j.ajt.2023.07.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 07/21/2023] [Accepted: 07/24/2023] [Indexed: 08/01/2023]
Abstract
Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult (≥18 years) DCD heart donors in the United States using the United Network for Organ Sharing registry. The registry does not identify potential donors who do not progress to circulatory death, and only those who progressed to death were included for analysis. Outcomes included organ recovery from the donor operating room and organ utilization for transplant. Multiple logistic regression was used to identify predictors of heart recovery and utilization. Among 558 DCD procurements, recovery occurred in 89.6%, and 92.5% of recovered hearts were utilized for transplant. Of 506 DCD procurements with available data, 65.0% were classified as direct procurement and perfusion and 35.0% were classified as normothermic regional perfusion (NRP). Logistic regression identified that NRP, shorter agonal time, younger donor age, and highest volume of organ procurement organizations were independently associated with increased odds for heart recovery. NRP independently predicted heart utilization after recovery. DCD heart utilization in the United States is satisfactory and consistent with international experience. NRP procurements have a higher yield for DCD heart transplantation compared with direct procurement and perfusion, which may reflect differences in donor assessment and acceptance criteria.
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Affiliation(s)
- Jennie H Kwon
- Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Benjamin Usry
- Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Zubair A Hashmi
- Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Krishna Bhandari
- Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Anthony P Carnicelli
- Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Ryan J Tedford
- Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Brett A Welch
- Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Khaled Shorbaji
- Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Arman Kilic
- Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
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21
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Panconesi R, Carvalho MF, Eden J, Fazi M, Ansari F, Mancina L, Navari N, Sousa Da Silva RX, Dondossola D, Borrego LB, Pietzke M, Peris A, Meierhofer D, Muiesan P, Galkin A, Marra F, Dutkowski P, Schlegel A. Mitochondrial injury during normothermic regional perfusion (NRP) and hypothermic oxygenated perfusion (HOPE) in a rodent model of DCD liver transplantation. EBioMedicine 2023; 98:104861. [PMID: 37924707 PMCID: PMC10660010 DOI: 10.1016/j.ebiom.2023.104861] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 10/15/2023] [Accepted: 10/16/2023] [Indexed: 11/06/2023] Open
Abstract
BACKGROUND Normothermic regional perfusion (NRP) and hypothermic-oxygenated-perfusion (HOPE), were both shown to improve outcomes after liver transplantation from donors after circulatory death (DCD). Comparative clinical and mechanistical studies are however lacking. METHODS A rodent model of NRP and HOPE, both in the donor, was developed. Following asystolic donor warm ischemia time (DWIT), the abdominal compartment was perfused either with a donor-blood-based-perfusate at 37 °C (NRP) or with oxygenated Belzer-MPS at 10 °C (donor-HOPE) for 2 h. Livers were then procured and underwent 5 h static cold storage (CS), followed by transplantation. Un-perfused and HOPE-treated DCD-livers (after CS) and healthy livers (DBD) with direct implantation after NRP served as controls. Endpoints included the entire spectrum of ischemia-reperfusion-injury. FINDINGS Healthy control livers (DBD) showed minimal signs of inflammation during 2 h NRP and achieved 100% posttransplant recipient survival. In contrast, DCD livers with 30 and 60 min DWIT suffered from greater mitochondrial injury and inflammation as measured by increased perfusate Lactate, FMN- and HMGB-1-levels with subsequent Toll-like-receptor activation during NRP. In contrast, donor-HOPE (instead of NRP) led to significantly less mitochondrial-complex-I-injury and inflammation. Results after donor-HOPE were comparable to ex-situ HOPE after CS. Most DCD-liver recipients survived when treated with one HOPE-technique (86%), compared to only 40% after NRP (p = 0.0053). Following a reduction of DWIT (15 min), DCD liver recipients achieved comparable survivals with NRP (80%). INTERPRETATION High-risk DCD livers benefit more from HOPE-treatment, either immediately in the donor or after cold storage. Comparative prospective clinical studies are required to translate the results. FUNDING Funding was provided by the Swiss National Science Foundation (grant no: 32003B-140776/1, 3200B-153012/1, 320030-189055/1, and 31IC30-166909) and supported by University Careggi (grant no 32003B-140776/1) and the OTT (grant No.: DRGT641/2019, cod.prog. 19CT03) and the Max Planck Society. Work in the A.G. laboratory was partially supported by the NIH R01NS112381 and R21NS125466 grants.
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Affiliation(s)
- Rebecca Panconesi
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10124, Turin, Italy; Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland
| | | | - Janina Eden
- Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland
| | - Marilena Fazi
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Fariha Ansari
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY, 10065, USA
| | - Leandro Mancina
- Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland
| | - Nadia Navari
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Richard Xavier Sousa Da Silva
- Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland
| | - Daniele Dondossola
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
| | - Lucia Bautista Borrego
- Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland
| | - Matthias Pietzke
- Max Planck Institute for Molecular Genetics, Mass Spectrometry Facility, 14195, Berlin, Germany
| | - Adriano Peris
- Tuscany Regional Transplant Authority, Centro Regionale Allocazione Organi e Tessuti (CRAOT), Florence, Italy
| | - David Meierhofer
- Max Planck Institute for Molecular Genetics, Mass Spectrometry Facility, 14195, Berlin, Germany
| | - Paolo Muiesan
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY, 10065, USA
| | - Alexander Galkin
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY, 10065, USA
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy
| | - Philipp Dutkowski
- Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland
| | - Andrea Schlegel
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, Zurich, Switzerland; General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy; Transplantation Center, Digestive Disease and Surgery Institute and Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
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22
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Camagni S, Amaduzzi A, Grazioli L, Ghitti D, Pasulo L, Pinelli D, Fagiuoli S, Colledan M. Extended criteria liver donation after circulatory death with prolonged warm ischemia: a pilot experience of normothermic regional perfusion and no subsequent ex-situ machine perfusion. HPB (Oxford) 2023; 25:1494-1501. [PMID: 37659903 DOI: 10.1016/j.hpb.2023.07.902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 07/11/2023] [Accepted: 07/21/2023] [Indexed: 09/04/2023]
Abstract
BACKGROUND Livers from controlled donation after circulatory death (cDCD) with very prolonged warm ischemic time (WIT) are regularly transplanted after abdominal normothermic regional perfusion (aNRP) plus ex-situ machine perfusion (MP). Considering aNRP as in-situ MP, we investigated whether the results of a pilot experience of extended criteria cDCD liver transplantation (LT) with prolonged WIT, with aNRP alone, were comparable to the best possible outcomes in low-risk cDCD LT. METHODS Prospectively collected data on 24 cDCD LT, with aNRP alone, were analyzed. RESULTS The median total and asystolic WIT were 51 and 25 min. Measures within benchmark cut-offs were: median duration of surgery (5.9 h); median intraoperative transfusions (3 units of red blood cells); need for renal replacement therapy (2/24 patients); median intensive care stay (3 days); key complications; overall morbidity, graft loss, and retransplantation up to 12 months; 12-month mortality (2/21 patients). The median hospital stay (33 days, due to logistics) and mortality up to 6 months (2/24 patients, due to graft-unrelated causes) exceeded benchmark thresholds. CONCLUSIONS This pilot experience suggests that livers from cDCD with very prolonged WIT that appear viable during adequate quality aNRP may be safely transplanted, with no need for ex-situ MP, with considerable resource savings.
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Affiliation(s)
- Stefania Camagni
- Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy.
| | - Annalisa Amaduzzi
- Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy
| | - Lorenzo Grazioli
- Department of Anesthesia and Intensive Care, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy
| | - Davide Ghitti
- Department of Anesthesia and Intensive Care, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy
| | - Luisa Pasulo
- Gastroenterology and Transplant Hepatology, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy
| | - Domenico Pinelli
- Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy
| | - Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy; Università degli Studi di Milano-Bicocca, Piazza dell'Ateneo Nuovo, 20126 Milano, Italy
| | - Michele Colledan
- Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy; Università degli Studi di Milano-Bicocca, Piazza dell'Ateneo Nuovo, 20126 Milano, Italy
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23
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Taj R, Olaso D, Schnickel GT, Brubaker AL. Practice Patterns of Liver Allograft Acceptance From Donors After Circulatory Death at US Transplant Centers. Transplant Proc 2023; 55:S0041-1345(23)00579-1. [PMID: 39492063 DOI: 10.1016/j.transproceed.2023.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 07/28/2023] [Accepted: 08/16/2023] [Indexed: 11/05/2024]
Abstract
BACKGROUND United States transplant centers have low rates of liver allograft utilization from donation after circulatory death (DCD) donors. Prolonged functional donor warm ischemic time (f-DWIT) is associated with worse outcomes; however, center practices regarding f-DWIT are unclear. As emerging technologies are changing the landscape of DCD liver transplantation, this study aims to gain insights into the practices of US centers around DCD liver allograft utilization. METHODS An electronic survey was distributed to transplant surgeons at US transplant centers from May to July 2022. RESULTS Responses were received from 108 transplant surgeons, of which, 44.4% reported their center's annual DCD liver transplant volume as <10%, and 40.7% reported volumes of 10% to 30%. Warm ischemic time (WIT) was the principal donor variable considered by accepting surgeons (72.2%). Center definition of f-DWIT varied widely, with at least 14 definitions being used. Nearly half of the surgeons (48.6%) defined f-DWIT as time from systolic blood pressure (SBP) <80 mm Hg or oxygen saturation (Sp02) <80% to flush; 21.5% defined f-DWIT as ≤30 minutes from withdrawal of life-sustaining therapy to flush. Nearly 13% of centers use normothermic machine perfusion for most of their DCD liver allografts. More than half of surgeons transplanted at least 1 DCD liver allograft recovered after normothermic regional perfusion. CONCLUSIONS Differences in the definition of f-DWIT and acceptance patterns of DCD liver allografts limit the ability to evaluate patient and allograft outcomes. As the DCD landscape is evolving, consensus definitions and granular databases can improve the transplant community's ability to evaluate outcome data and utilization from DCD liver allografts.
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Affiliation(s)
- Raeda Taj
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, California.
| | - Danae Olaso
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, California
| | - Gabriel T Schnickel
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, California
| | - Aleah L Brubaker
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, California
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24
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Steinberg I, Patrono D, De Cesaris E, Lucà M, Catalano G, Marro M, Rizza G, Simonato E, Brazzi L, Romagnoli R, Zanierato M. Viability assessment of livers donated after circulatory determination of death during normothermic regional perfusion. Artif Organs 2023; 47:1592-1603. [PMID: 37548353 DOI: 10.1111/aor.14622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/14/2023] [Accepted: 07/25/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND Abdominal normothermic regional perfusion (A-NRP) allows in-situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A-NRP. METHODS To refine liver viability assessment during A-NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A-NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded. RESULTS Twenty-seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r2 = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A-NRP was comparable, whereas oxygen consumption (VO2 ) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO2 ) and VO2 . Lactate clearance was correlated to transaminase levels and DO2 -normalized lactate clearance was the parameter best discriminating between study groups. CONCLUSIONS DO2 -normalized lactate clearance may represent an element of liver viability assessment during A-NRP.
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Affiliation(s)
- Irene Steinberg
- Department of Anesthesia and Critical Care, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
- Department of Surgical Sciences, University of Turin, Turin, Italy
- Department of Mechanical and Aerospace Engineering, Polytechnic University of Turin, Turin, Italy
| | - Damiano Patrono
- General Surgery 2U - Liver Transplant Center, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Enrico De Cesaris
- Department of Anesthesia and Critical Care, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Michele Lucà
- Department of Anesthesia and Critical Care, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Giorgia Catalano
- General Surgery 2U - Liver Transplant Center, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Matteo Marro
- Cardiovascular Surgery, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Giorgia Rizza
- General Surgery 2U - Liver Transplant Center, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Erika Simonato
- Cardiovascular Surgery, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Luca Brazzi
- Department of Anesthesia and Critical Care, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
- Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Renato Romagnoli
- Department of Surgical Sciences, University of Turin, Turin, Italy
- General Surgery 2U - Liver Transplant Center, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Marinella Zanierato
- Department of Anesthesia and Critical Care, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
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25
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Tingle SJ, Dobbins JJ, Thompson ER, Figueiredo RS, Mahendran B, Pandanaboyana S, Wilson C. Machine perfusion in liver transplantation. Cochrane Database Syst Rev 2023; 9:CD014685. [PMID: 37698189 PMCID: PMC10496129 DOI: 10.1002/14651858.cd014685.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/13/2023]
Abstract
BACKGROUND Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box). OBJECTIVES To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023. SELECTION CRITERIA We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi-randomised studies to assess treatment harms. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non-function of the graft, 7. early allograft function, 8. non-serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post-transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence. MAIN RESULTS We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two-group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion. When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I2 = 0%; 4 trials, 482 recipients; low-certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low-certainty evidence due to imprecision and risk of bias). No trials reported quality of life. When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I2 = 0%; 4 trials, 482 recipients; high-certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I2 = 0%; 2 trials, 156 participants; moderate-certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high-certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown. We identified 11 ongoing studies investigating machine perfusion technologies. AUTHORS' CONCLUSIONS In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.
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Affiliation(s)
- Samuel J Tingle
- NIHR Blood and Transplant Research Unit, Newcastle University and Cambridge University, Newcastle upon Tyne, UK
| | | | - Emily R Thompson
- Institute of Transplantation, The Freeman Hospital, Newcastle upon Tyne, UK
| | | | | | - Sanjay Pandanaboyana
- HPB and Liver Transplant Surgery, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Colin Wilson
- Institute of Transplantation, The Freeman Hospital, Newcastle upon Tyne, UK
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Brubaker AL, Taj R, Jackson B, Lee A, Tsai C, Berumen J, Parekh JR, Mekeel KL, Gupta AR, Gardner JM, Chaly T, Mathur AK, Jadlowiec C, Reddy S, Nunez R, Bellingham J, Thomas EM, Wellen JR, Pan JH, Kearns M, Pretorius V, Schnickel GT. Early patient and liver allograft outcomes from donation after circulatory death donors using thoracoabdominal normothermic regional: a multi-center observational experience. FRONTIERS IN TRANSPLANTATION 2023; 2:1184620. [PMID: 38993873 PMCID: PMC11235322 DOI: 10.3389/frtra.2023.1184620] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Accepted: 07/17/2023] [Indexed: 07/13/2024]
Abstract
Background Donation after circulatory death (DCD) liver allografts are associated with higher rates of primary non-function (PNF) and ischemic cholangiopathy (IC). Advanced recovery techniques, including thoracoabdominal normothermic regional perfusion (TA-NRP), may improve organ utilization and patient and allograft outcomes. Given the increasing US experience with TA-NRP DCD recovery, we evaluated outcomes of DCD liver allografts transplanted after TA-NRP. Methods Liver allografts transplanted from DCD donors after TA-NRP were identified from 5/1/2021 to 1/31/2022 across 8 centers. Donor data included demographics, functional warm ischemic time (fWIT), total warm ischemia time (tWIT) and total time on TA-NRP. Recipient data included demographics, model of end stage liver disease (MELD) score, etiology of liver disease, PNF, cold ischemic time (CIT), liver function tests, intensive care unit (ICU) and hospital length of stay (LOS), post-operative transplant related complications. Results The donors' median age was 32 years old and median BMI was 27.4. Median fWIT was 20.5 min; fWIT exceeded 30 min in two donors. Median time to initiation of TA-NRP was 4 min and median time on bypass was 66 min. The median recipient listed MELD and MELD at transplant were 22 and 21, respectively. Median allograft CIT was 292 min. The median length of follow up was 257 days. Median ICU and hospital LOS were 2 and 7 days, respectively. Three recipients required management of anastomotic biliary strictures. No patients demonstrated IC, PNF or required re-transplantation. Conclusion Liver allografts from TA-NRP DCD donors demonstrated good early allograft and recipient outcomes.
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Affiliation(s)
- Aleah L. Brubaker
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, CA, United States
| | - Raeda Taj
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, CA, United States
| | - Brandon Jackson
- Department of Surgery, Division of Cardiothoracic Surgery, UC San Diego, San Diego, CA, United States
| | - Arielle Lee
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, CA, United States
| | - Catherine Tsai
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, CA, United States
| | - Jennifer Berumen
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, CA, United States
| | - Justin R. Parekh
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, CA, United States
| | - Kristin L. Mekeel
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, CA, United States
| | - Alexander R. Gupta
- Department of Surgery, Division of Transplant Surgery, UC San Francisco, San Francisco, CA, United States
| | - James M. Gardner
- Department of Surgery, Division of Transplant Surgery, UC San Francisco, San Francisco, CA, United States
| | - Thomas Chaly
- Arizona Transplant Associates, Phoenix, AZ, United States
| | - Amit K. Mathur
- Department of Surgery, Division of Transplant Surgery, Mayo Clinic Arizona, Phoenix, AZ, United States
| | - Caroline Jadlowiec
- Department of Surgery, Division of Transplant Surgery, Mayo Clinic Arizona, Phoenix, AZ, United States
| | - Sudhakar Reddy
- Department of Surgery, Division of Transplant Surgery, Mayo Clinic Arizona, Phoenix, AZ, United States
| | - Rafael Nunez
- Department of Surgery, Division of Transplant Surgery, Mayo Clinic Arizona, Phoenix, AZ, United States
| | - Janet Bellingham
- Department of Transplantation, California Pacific Medical Center, San Francisco, CA, United States
| | - Elizabeth M. Thomas
- Department of Surgery, University Transplant Center, University of Texas Health San Antonio, San Antonio, TX, United States
| | - Jason R. Wellen
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St Louis, MO, United States
| | - Jenny H. Pan
- Department of Surgery, Division of Abdominal Transplantation, Stanford University, Stanford, CA, United States
| | - Mark Kearns
- Department of Surgery, Division of Cardiothoracic Surgery, UC San Diego, San Diego, CA, United States
| | - Victor Pretorius
- Department of Surgery, Division of Cardiothoracic Surgery, UC San Diego, San Diego, CA, United States
| | - Gabriel T. Schnickel
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, UC San Diego, San Diego, CA, United States
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27
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Basta G, Melandro F, Babboni S, Del Turco S, Ndreu R, Torri F, Martinelli C, Silvestrini B, Peris A, Lazzeri C, Guarracino F, Morganti R, Maremmani P, Bertini P, De Simone P, Ghinolfi D. An extensive evaluation of hepatic markers of damage and regeneration in controlled and uncontrolled donation after circulatory death. Liver Transpl 2023; 29:813-826. [PMID: 36879554 DOI: 10.1097/lvt.0000000000000122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 02/17/2023] [Indexed: 03/08/2023]
Abstract
Livers from donations after circulatory death (DCDs) are very sensitive to ischemia/reperfusion injury and thus need careful reconditioning, such as normothermic regional perfusion (NRP). So far, its impact on DCDs has not been thoroughly investigated. This pilot cohort study aimed to explore the NRP impact on liver function by evaluating dynamic changes of circulating markers and hepatic gene expression in 9 uncontrolled DCDs (uDCDs) and 10 controlled DCDs. At NRP start, controlled DCDs had lower plasma levels of inflammatory and liver damage markers, including α-glutathione s-transferase, sorbitol-dehydrogenase, malate dehydrogenase 1, liver-type arginase-1, and keratin-18, but higher levels of osteopontin, sFas, flavin mononucleotide, and succinate than uDCDs. During 4-hour NRP, some damage and inflammatory markers increased in both groups, while IL-6, HGF, and osteopontin increased only in uDCDs. At the NRP end, the tissue expression of early transcriptional regulators, apoptosis, and autophagy mediators was higher in uDCDs than in controlled DCDs. In conclusion, despite initial differences in liver damage biomarkers, the uDCD group was characterized by a major gene expression of regenerative and repair factors after the NRP procedure. Correlative analysis among circulating/tissue biomarkers and the tissue congestion/necrosis degree revealed new potential candidate biomarkers.
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Affiliation(s)
- Giuseppina Basta
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Fabio Melandro
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Serena Babboni
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Serena Del Turco
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Rudina Ndreu
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Francesco Torri
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Caterina Martinelli
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | | | - Adriano Peris
- Tuscany Regional Transplant Authority, Centro Regionale Allocazione Organi e Tessuti (CRAOT), Florence, Italy
| | - Chiara Lazzeri
- Tuscany Regional Transplant Authority, Centro Regionale Allocazione Organi e Tessuti (CRAOT), Florence, Italy
| | - Fabio Guarracino
- Department of Anesthesia and Critical Care Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Riccardo Morganti
- Division of Medical Statistics, University of Pisa Medical School Hospital, Pisa, Italy
| | - Paolo Maremmani
- Department of Anesthesia and Critical Care Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Pietro Bertini
- Department of Anesthesia and Critical Care Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Paolo De Simone
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Davide Ghinolfi
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
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28
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Wall A, Rosenzweig M, McKenna GJ, Ma TW, Asrani SK, Testa G. Six-month abdominal transplant recipient outcomes from donation after circulatory death heart donors: A retrospective analysis by procurement technique. Am J Transplant 2023; 23:987-995. [PMID: 37088143 DOI: 10.1016/j.ajt.2023.04.021] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 04/07/2023] [Accepted: 04/19/2023] [Indexed: 04/25/2023]
Abstract
Standard US practice for donation after circulatory death (DCD) abdominal organ procurement is superrapid recovery (SRR). A newer approach using thoracoabdominal normothermic regional perfusion (TA-NRP) shows promise for better recipient outcomes for all organs, but there are few reports of abdominal recipient outcomes from TA-NRP donors. We used the United Network for Organ Sharing data to identify all cardiac DCD donors from October 1, 2020, to May 20, 2022, and categorized them by recovery procedure (SRR vs TA-NRP). We then identified all liver, kidney, and pancreas recipients of these donors for whom 6-month outcome data were available and compared patient and graft survival, kidney delayed graft function (DGF), and biliary complications between TA-NRP DCD and SRR DCD organ recipients. Patient and graft survival did not differ significantly between groups for either kidney or liver recipients. Significantly fewer TA-NRP kidney recipients developed DGF (12.7% [15/118] vs 42.0% [84/200], P <.001), and TA-NRP and pumped kidneys had lower odds for DGF on multivariate analysis. No liver recipients in either group had biliary complications or were relisted for transplantation for ischemic cholangiopathy. Although long-term outcomes need to be investigated, our early results show similar outcomes for recipients of TA-NRP DCD abdominal organs versus recipients of SRR DCD abdominal organs. We believe that TA-NRP is an effective approach to expand the use of DCD organs.
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Affiliation(s)
- Anji Wall
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA.
| | - Matthew Rosenzweig
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA
| | - Gregory J McKenna
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA
| | - Tsung-Wei Ma
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA
| | - Sumeet K Asrani
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA
| | - Giuliano Testa
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA
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29
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Patrono D, De Stefano N, Vissio E, Apostu AL, Petronio N, Vitelli G, Catalano G, Rizza G, Catalano S, Colli F, Chiusa L, Romagnoli R. How to Preserve Steatotic Liver Grafts for Transplantation. J Clin Med 2023; 12:3982. [PMID: 37373676 DOI: 10.3390/jcm12123982] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 06/05/2023] [Accepted: 06/08/2023] [Indexed: 06/29/2023] Open
Abstract
Liver allograft steatosis is a significant risk factor for postoperative graft dysfunction and has been associated with inferior patient and graft survival, particularly in the case of moderate or severe macrovesicular steatosis. In recent years, the increasing incidence of obesity and fatty liver disease in the population has led to a higher proportion of steatotic liver grafts being used for transplantation, making the optimization of their preservation an urgent necessity. This review discusses the mechanisms behind the increased susceptibility of fatty livers to ischemia-reperfusion injury and provides an overview of the available strategies to improve their utilization for transplantation, with a focus on preclinical and clinical evidence supporting donor interventions, novel preservation solutions, and machine perfusion techniques.
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Affiliation(s)
- Damiano Patrono
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Nicola De Stefano
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Elena Vissio
- Department of Pathology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Ana Lavinia Apostu
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Nicoletta Petronio
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Giovanni Vitelli
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Giorgia Catalano
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Giorgia Rizza
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Silvia Catalano
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Fabio Colli
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Luigi Chiusa
- Department of Pathology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Renato Romagnoli
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
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30
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De Carlis R, Paolo Muiesan, Taner B. Donation after circulatory death: Novel strategies to improve the liver transplant outcome. J Hepatol 2023; 78:1169-1180. [PMID: 37208104 DOI: 10.1016/j.jhep.2023.04.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 04/07/2023] [Accepted: 04/11/2023] [Indexed: 05/21/2023]
Abstract
In many countries, donation after circulatory death (DCD) liver grafts are used to overcome organ shortages; however, DCD grafts have been associated with an increased risk of complications and even graft loss after liver transplantation. The increased risk of complications is thought to correlate with prolonged functional donor warm ischaemia time. Stringent donor selection criteria and utilisation of in situ and ex situ organ perfusion technologies have led to improved outcomes. Additionally, the increased use of novel organ perfusion strategies has led to the possibility of reconditioning marginal DCD liver grafts. Moreover, these technologies enable the assessment of liver function before implantation, thus providing valuable data that can guide more precise graft-recipient selection. In this review, we first describe the different definitions of functional warm donor ischaemia time and its role as a determinant of outcomes after DCD liver transplantation, with a focus on the thresholds proposed for graft acceptance. Next, organ perfusion strategies, namely normothermic regional perfusion, hypothermic oxygenated perfusion, and normothermic machine perfusion are discussed. For each technique, clinical studies reporting on the transplant outcome are described, together with a discussion on the possible protective mechanisms involved and the functional criteria adopted for graft selection. Finally, we review multimodal preservation protocols involving a combination of more than one perfusion technique and potential future directions in the field.
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Affiliation(s)
- Riccardo De Carlis
- Division of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Ph.D. Course in Clinical and Experimental Sciences, University of Padua, Padua, Italy
| | - Paolo Muiesan
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
| | - Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, United States.
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31
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Watson CJ, MacDonald S, Bridgeman C, Brais R, Upponi SS, Foukaneli T, Swift L, Fear C, Selves L, Kosmoliaptsis V, Allison M, Hogg R, Parsy KS, Thomas W, Gaurav R, Butler AJ. D-dimer Release From Livers During Ex Situ Normothermic Perfusion and After In Situ Normothermic Regional Perfusion: Evidence for Occult Fibrin Burden Associated With Adverse Transplant Outcomes and Cholangiopathy. Transplantation 2023; 107:1311-1321. [PMID: 36728501 PMCID: PMC10205116 DOI: 10.1097/tp.0000000000004475] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 10/10/2022] [Accepted: 10/29/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Deceased donor livers are prone to biliary complications, which may necessitate retransplantation, and we, and others, have suggested that these complications are because of peribiliary vascular fibrin microthrombi. We sought to determine the prevalence and consequence of occult fibrin within deceased donor livers undergoing normothermic ex situ perfusion (NESLiP) and evaluate a role for fibrinolysis. METHODS D-dimer concentrations, products of fibrin degradation, were assayed in the perfusate of 163 livers taken after 2 h of NESLiP, including 91 that were transplanted. These were related to posttransplant outcomes. Five different fibrinolytic protocols during NESLiP using alteplase were evaluated, and the transplant outcomes of these alteplase-treated livers were reviewed. RESULTS Perfusate D-dimer concentrations were lowest in livers recovered using in situ normothermic regional perfusion and highest in alteplase-treated livers. D-dimer release from donation after brain death livers was significantly correlated with the duration of cold ischemia. In non-alteplase-treated livers, Cox proportional hazards regression analysis showed that D-dimer levels were associated with transplant survival ( P = 0.005). Treatment with alteplase and fresh frozen plasma during NESLiP was associated with significantly more D-dimer release into the perfusate and was not associated with excess bleeding postimplantation; 8 of the 9 treated livers were free of cholangiopathy, whereas the ninth had a proximal duct stricture. CONCLUSIONS Fibrin is present in many livers during cold storage and is associated with poor posttransplant outcomes. The amount of D-dimer released after fibrinolytic treatment indicates a significant occult fibrin burden and suggests that fibrinolytic therapy during NESLiP may be a promising therapeutic intervention.
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Affiliation(s)
- Christopher J.E. Watson
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Stephen MacDonald
- Specialist Haemostasis Laboratory, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Christopher Bridgeman
- Specialist Haemostasis Laboratory, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Rebecca Brais
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Department of Histopathology, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Sara S. Upponi
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Department of Radiology, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Theodora Foukaneli
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Department of Haematology, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Lisa Swift
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Corrina Fear
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Linda Selves
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Michael Allison
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
- Department of Medicine, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
| | - Rachel Hogg
- Statistics and Clinical Research, NHS Blood and Transplant, Bristol, United Kingdom
| | - Kourosh Saeb Parsy
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Will Thomas
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Specialist Haemostasis Laboratory, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Rohit Gaurav
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Andrew J. Butler
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
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Durán M, Calleja R, Hann A, Clarke G, Ciria R, Nutu A, Sanabria-Mateos R, Ayllón MD, López-Cillero P, Mergental H, Briceño J, Perera MTPR. Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant: What is the evidence? World J Gastroenterol 2023; 29:3066-3083. [PMID: 37346149 PMCID: PMC10280793 DOI: 10.3748/wjg.v29.i20.3066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 03/01/2023] [Accepted: 04/28/2023] [Indexed: 05/26/2023] Open
Abstract
The widespread uptake of different machine perfusion (MP) strategies for liver transplant has been driven by an effort to minimize graft injury. Damage to the cholangiocytes during the liver donation, preservation, or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage. This problem continues to trouble clinicians, and may have catastrophic consequences for the graft and patient. Ischemic injury, as a result of compromised hepatic artery flow, is a well-known cause of biliary strictures, sepsis, and graft failure. However, very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions (ITBL) that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise. Both the warm and cold ischemic period duration appear to influence the onset of ITBL. All of the commonly used MP techniques deliver oxygen to the graft cells, and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL. As clinical experience and published evidence grows for these modalities, the impact they have on ITBL rates is important to consider. In this review, the evidence for the three commonly used MP strategies (abdominal normothermic regional perfusion [A-NRP], hypothermic oxygenated perfusion [HOPE], and normothermic machine perfusion [NMP] for ITBL prevention has been critically reviewed. Inconsistencies with ITBL definitions used in trials, coupled with variations in techniques of MP, make interpretation challenging. Overall, the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage. The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.
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Affiliation(s)
- Manuel Durán
- Department of Liver Transplantation, Reina Sofía University Hospital, Córdoba 14004, Spain
| | - Rafael Calleja
- Department of Liver Transplantation, Reina Sofía University Hospital, Córdoba 14004, Spain
| | - Angus Hann
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - George Clarke
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - Ruben Ciria
- Department of Liver Transplantation, Reina Sofía University Hospital, Córdoba 14004, Spain
| | - Anisa Nutu
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
| | | | - María Dolores Ayllón
- Department of Liver Transplantation, Reina Sofía University Hospital, Córdoba 14004, Spain
| | - Pedro López-Cillero
- Department of Liver Transplantation, Reina Sofía University Hospital, Córdoba 14004, Spain
| | - Hynek Mergental
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - Javier Briceño
- Department of Liver Transplantation, Reina Sofía University Hospital, Córdoba 14004, Spain
| | - M Thamara P R Perera
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
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33
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Eden J, Sousa Da Silva R, Cortes-Cerisuelo M, Croome K, De Carlis R, Hessheimer AJ, 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 GC, de Jonge J, Lesurtel M, De Carlis LG, Taner CB, Heaton N, Schlegel A, Dutkowski P. Utilization of livers donated after circulatory death for transplantation - An international comparison. J Hepatol 2023; 78:1007-1016. [PMID: 36740047 DOI: 10.1016/j.jhep.2023.01.025] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/21/2023] [Accepted: 01/27/2023] [Indexed: 02/07/2023]
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 among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.
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Affiliation(s)
- Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - Richard Sousa Da Silva
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | | | - Kristopher Croome
- Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Amelia J Hessheimer
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
| | - Xavier Muller
- Department of Digestive Surgery & Liver Transplantation, Croix-Rousse Hospital, University of Lyon I, Lyon, France
| | - Femke de Goeij
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland
| | - Giulia Magini
- Division of Transplantation, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Philippe Compagnon
- Division of Transplantation, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Andreas Elmer
- Swisstransplant, The Swiss National Foundation for Organ Donation and Transplantation Effingerstrasse 1, 3011 Bern, Switzerland
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
| | - Rebecca Panconesi
- General Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10124 Turin, Italy
| | - Jeannette Widmer
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - Daniele Dondossola
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
| | - Paolo Muiesan
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
| | - Diethard Monbaliu
- Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium; Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | | | - Olivier Detry
- Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, Liege, Belgium
| | - Constantino Fondevila
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
| | - Ina Jochmans
- Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium; Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium; Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Franz Immer
- Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
| | - Gabriel C Oniscu
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Jeroen de Jonge
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Mickaël Lesurtel
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, University of Paris Cité, 100 Bd du Général Leclerc, 92110, Clichy, France
| | - Luciano G De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Andrea Schlegel
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland.
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Circelli A, Antonini MV, Nanni A, Prugnoli M, Gamberini E, Maitan S, Gecele C, Viola L, Bissoni L, Scognamiglio G, Mezzatesta L, Bergamini C, Gobbi L, Meca MCC, Sangiorgi G, Bisulli M, Spiga M, Pransani V, Liuzzi D, Fantini V, Catena F, Russo E, Agnoletti V. cDCD organ donation pathway of Romagna Local Health Authority: strategic planning, organizational management, and results. DISCOVER HEALTH SYSTEMS 2023; 2:12. [PMID: 37520516 PMCID: PMC10062274 DOI: 10.1007/s44250-023-00022-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Accepted: 02/03/2023] [Indexed: 04/03/2023]
Abstract
The introduction of pathways to enrol deceased donors after cardio-circulatory confirmation of death (donation after circulatory death, DCD) is expanding in many countries to face the shortage of organs for transplantation. The implementation of normothermic regional reperfusion (NRP) with warm oxygenated blood is a strategy to manage in-situ the organs of DCD donors. This approach, an alternative to in-situ cold preservation, and followed by prompt retrieval and cold static storage and/or ex-vivo machine perfusion (EVMP), could be limited to abdominal organs (A-NRP) or extended to the thorax (thoraco-abdominal, TA-NRP. NRP is also referred to as extracorporeal interval support for organ retrieval (EISOR). The use of EISOR is increasing in Europe, even if variably regulated. A-NRP has been demonstrated to be effective in decreasing the risk associated with transplantation of abdominal organs from DCD donors, and was recommended by the European Society for Organ Transplantation (ESOT) in a recent consensus document. We aim to explain how we select the candidates for DCD, to describe our regionalized model for implementing EISOR provision, and to introduce the health care professionals involved in this complex process, with their strictly defined roles, responsibilities, and boundaries. Finally, we report the results of our program, recruiting cDCD donors over a large network of hospitals, all pertaining to a Local Health Authority (Azienda Unità Sanitaria Locale, AUSL) in Romagna, Italy.
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Affiliation(s)
- Alessandro Circelli
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Marta Velia Antonini
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena & Reggio Emilia, Emilia-Romagna, Italy
| | - Andrea Nanni
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
- Transplant Procurement Management-AUSL della Romagna, Cesena, Italy
| | - Manila Prugnoli
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
- Transplant Procurement Management-AUSL della Romagna, Cesena, Italy
| | - Emiliano Gamberini
- Anesthesia and Intensive Care Unit, Infermi Hospital, AUSL della Romagna, Rimini, Italy
| | - Stefano Maitan
- Intensive Care Unit, Morgagni-Pierantoni Hospital-AUSL della Romagna, Forlì, Italy
| | - Claudio Gecele
- Anesthesia and Intensive Care Unit, Santa Maria delle Croci Hospital, Ravenna, Italy
| | - Lorenzo Viola
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Luca Bissoni
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Giovanni Scognamiglio
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Luca Mezzatesta
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Carlo Bergamini
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Luca Gobbi
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | | | | | - Marcello Bisulli
- Interventional Radiology Department, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Martina Spiga
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Veruska Pransani
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Daria Liuzzi
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Valentina Fantini
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Fausto Catena
- General and Emergency Surgery, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Emanuele Russo
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
| | - Vanni Agnoletti
- Anesthesia and Intensive Care Unit, Bufalini Hospital-AUSL della Romagna, Cesena, Italy
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Miñambres E, Estébanez B, Ballesteros MÁ, Coll E, Flores-Cabeza EM, Mosteiro F, Lara R, Domínguez-Gil B. Normothermic Regional Perfusion in Pediatric Controlled Donation After Circulatory Death Can Lead to Optimal Organ Utilization and Posttransplant Outcomes. Transplantation 2023; 107:703-708. [PMID: 36226852 DOI: 10.1097/tp.0000000000004326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
BACKGROUND The benefits of normothermic regional perfusion (NRP) in posttransplant outcomes after controlled donation after the determination of death by circulatory criteria (cDCD) has been shown in different international adult experiences. However, there is no information on the use of NRP in pediatric cDCD donors. METHODS This is a multicenter, retrospective, observational cohort study describing the pediatric (<18 y) cDCD procedures performed in Spain, using either abdominal NRP or thoracoabdominal NRP and the outcomes of recipients of the obtained organs. RESULTS Thirteen pediatric cDCD donors (age range, 2-17 y) subject to abdominal NRP or thoracoabdominal NRP were included. A total of 46 grafts (24 kidneys, 11 livers, 8 lungs, 2 hearts, and 1 pancreas) were finally transplanted (3.5 grafts per donor). The mean functional warm ischemic time was 15 min (SD 6 min)' and the median duration of NRP was 87 min (interquartile range, 69-101 min). One-year noncensored for death kidney graft survival was 91.3%. The incidence of delayed graft function was 13%. One-year' noncensored-for-death liver graft survival was 90.9%. All lung and pancreas recipients had an excellent evolution. One heart recipient died due to a septic shock. CONCLUSIONS This is the largest experience of pediatric cDCD using NRP as graft preservation method. Although our study has several limitations, such as its retrospective nature and the small sample size, its reveals that NRP may increase the utilization of cDCD pediatric organs and offer optimal recipients' outcomes.
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Affiliation(s)
- Eduardo Miñambres
- Transplant Coordination Unit & Service of Intensive Care, University Hospital Marqués de Valdecilla-IDIVAL, Santander, Spain
- School of Medicine, Universidad de Cantabria, Santander, Spain
| | - Belen Estébanez
- Transplant Coordination Unit & Service of Intensive Care, University Hospital La Paz, Madrid, Spain
| | - Maria Ángeles Ballesteros
- Transplant Coordination Unit & Service of Intensive Care, University Hospital Marqués de Valdecilla-IDIVAL, Santander, Spain
| | | | | | - Fernando Mosteiro
- Transplant Coordination Unit & Service of Intensive Care, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain
| | - Ramón Lara
- Transplant Coordination Unit & Service of Intensive Care, University Hospital Virgen De Las Nieves, Granada, Spain
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36
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Quandahl R, Vanneman MW, Wilke TJ, Kassel CA. 2022 Clinical Updates in Liver Transplantation. J Cardiothorac Vasc Anesth 2023:S1053-0770(23)00116-7. [PMID: 36964080 DOI: 10.1053/j.jvca.2023.02.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 02/15/2023] [Indexed: 02/25/2023]
Affiliation(s)
- Rachel Quandahl
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE
| | - Matthew W Vanneman
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA
| | - Trevor J Wilke
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE
| | - Cale A Kassel
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE.
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37
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Oniscu GC, Mehew J, Butler AJ, Sutherland A, Gaurav R, Hogg R, Currie I, Jones M, Watson CJE. Improved Organ Utilization and Better Transplant Outcomes With In Situ Normothermic Regional Perfusion in Controlled Donation After Circulatory Death. Transplantation 2023; 107:438-448. [PMID: 35993664 DOI: 10.1097/tp.0000000000004280] [Citation(s) in RCA: 87] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND . We evaluated whether the use of normothermic regional perfusion (NRP) was associated with increased organ recovery and improved transplant outcomes from controlled donation after circulatory death (cDCD). METHODS . This is a retrospective analysis of UK adult cDCD donors' where at least 1 abdominal organ was accepted for transplantation between January 1, 2011, and December 31, 2019. RESULTS . A mean of 3.3 organs was transplanted when NRP was used compared with 2.6 organs per donor when NRP was not used. When adjusting for organ-specific donor risk profiles, the use of NRP increased the odds of all abdominal organs being transplanted by 3-fold for liver ( P < 0.0001; 95% confidence interval [CI], 2.20-4.29), 1.5-fold for kidney ( P = 0.12; 95% CI, 0.87-2.58), and 1.6-fold for pancreas ( P = 0.0611; 95% CI, 0.98-2.64). Twelve-mo liver transplant survival was superior for recipients of a cDCD NRP graft with a 51% lower risk-adjusted hazard of transplant failure (HR = 0.494). In risk-adjusted analyses, NRP kidneys had a 35% lower chance of developing delayed graft function than non-NRP kidneys (odds ratio, 0.65; 95% CI, 0.465-0.901)' and the expected 12-mo estimated glomerular filtration rate was 6.3 mL/min/1.73 m 2 better if abdominal NRP was used ( P < 0.0001). CONCLUSIONS . The use of NRP during DCD organ recovery leads to increased organ utilization and improved transplant outcomes compared with conventional organ recovery.
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Affiliation(s)
- Gabriel C Oniscu
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh, United Kingdom
- Department of Clinical Surgery, University of Edinburgh, Edinburgh, United Kingdom
| | - Jennifer Mehew
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Andrew J Butler
- University of Cambridge Department of Surgery, Addenbrooke's Hospital, Cambridge, the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), London, United Kingdom
- Cambridge Transplant Unit, Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital, Bristol, United Kingdom
| | - Andrew Sutherland
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh, United Kingdom
- Department of Clinical Surgery, University of Edinburgh, Edinburgh, United Kingdom
| | - Rohit Gaurav
- Cambridge Transplant Unit, Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital, Bristol, United Kingdom
| | - Rachel Hogg
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Ian Currie
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh, United Kingdom
- Department of Clinical Surgery, University of Edinburgh, Edinburgh, United Kingdom
| | - Mark Jones
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Christopher J E Watson
- University of Cambridge Department of Surgery, Addenbrooke's Hospital, Cambridge, the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), London, United Kingdom
- Cambridge Transplant Unit, Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital, Bristol, United Kingdom
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38
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Blondeel J, Monbaliu D, Gilbo N. Dynamic liver preservation: Are we still missing pieces of the puzzle? Artif Organs 2023; 47:248-259. [PMID: 36227006 DOI: 10.1111/aor.14397] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 08/11/2022] [Indexed: 02/03/2023]
Abstract
To alleviate the persistent shortage of donor livers, high-risk liver grafts are increasingly being considered for liver transplantation. Conventional preservation with static cold storage falls short in protecting these high-risk livers from ischemia-reperfusion injury, as evident from higher rates of post-transplant complications such as early allograft dysfunction and ischemic cholangiopathy. Moreover, static cold storage does not allow for a functional assessment of the liver prior to transplantation. To overcome these limitations, dynamic strategies of liver preservation have been proposed, designed to provide a protective effect while allowing pre-transplant functional assessment. In this review, we discuss how different dynamic preservation strategies exert their effects, where we stand in assessing liver function and what challenges are lying ahead.
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Affiliation(s)
- Joris Blondeel
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Nicholas Gilbo
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
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39
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Mohkam K, Nasralla D, Mergental H, Muller X, Butler A, Jassem W, Imber C, Monbaliu D, Perera MTPR, Laing RW, García‐Valdecasas JC, Paul A, Dondero F, Cauchy F, Savier E, Scatton O, Robin F, Sulpice L, Bucur P, Salamé E, Pittau G, Allard M, Pradat P, Rossignol G, Mabrut J, Ploeg RJ, Friend PJ, Mirza DF, Lesurtel M, Consortium for Organ Preservation in Europe (COPE). In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death. Liver Transpl 2022; 28:1716-1725. [PMID: 35662403 PMCID: PMC9796010 DOI: 10.1002/lt.26522] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 03/14/2022] [Accepted: 03/19/2022] [Indexed: 12/30/2022]
Abstract
In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.
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Affiliation(s)
- Kayvan Mohkam
- Department of Digestive Surgery & Liver Transplantation, Croix‐Rousse Hospital, Hospices Civils de LyonClaude Bernard Lyon 1 UniversityLyonFrance
| | - David Nasralla
- Department of Hepatopancreatobiliary and Liver Transplant SurgeryRoyal Free HospitalLondonUK
| | - Hynek Mergental
- Liver Unit, Queen Elizabeth HospitalUniversity Hospitals BirminghamBirminghamUK
| | - Xavier Muller
- Department of Digestive Surgery & Liver Transplantation, Croix‐Rousse Hospital, Hospices Civils de LyonClaude Bernard Lyon 1 UniversityLyonFrance
| | - Andrew Butler
- Department of Surgery, Addenbrooke's HospitalUniversity of CambridgeCambridgeUK
| | - Wayel Jassem
- Institute of Liver StudiesKing's College HospitalLondonUK
| | - Charles Imber
- Department of Hepatopancreatobiliary and Liver Transplant SurgeryRoyal Free HospitalLondonUK
| | - Diethard Monbaliu
- Abdominal Transplant Surgery Unit, Department of SurgeryUniversity Hospitals LeuvenLeuvenBelgium
| | | | - Richard W. Laing
- Liver Unit, Queen Elizabeth HospitalUniversity Hospitals BirminghamBirminghamUK
| | | | - Andreas Paul
- Department of General, Visceral and Transplantation SurgeryUniversity Hospital EssenEssenGermany
| | - Federica Dondero
- Department of Hepatobiliopancreatic SurgeryDepartment of Hepatopancreatobiliary Surgery and Liver TransplantationBeaujon Hospital, Assitance Publique‐Hôpitaux de Paris (AP‐HP), University Paris CitéClichyFrance
| | - François Cauchy
- Department of Hepatobiliopancreatic SurgeryDepartment of Hepatopancreatobiliary Surgery and Liver TransplantationBeaujon Hospital, Assitance Publique‐Hôpitaux de Paris (AP‐HP), University Paris CitéClichyFrance
| | - Eric Savier
- Department of Hepatobiliary Surgery and Liver Transplantation, Pitié‐Salpêtrière HospitalSorbonne UniversityParisFrance
| | - Olivier Scatton
- Department of Hepatobiliary Surgery and Liver Transplantation, Pitié‐Salpêtrière HospitalSorbonne UniversityParisFrance
| | - Fabien Robin
- Department of Hepatobiliary and Digestive SurgeryPontchaillou University HospitalRennesFrance
| | - Laurent Sulpice
- Department of Hepatobiliary and Digestive SurgeryPontchaillou University HospitalRennesFrance
| | - Petru Bucur
- Department of Digestive, Oncological, Endocrine, Hepato‐Biliary, Pancreatic and Liver Transplant SurgeryTrousseau HospitalToursFrance
| | - Ephrem Salamé
- Department of Digestive, Oncological, Endocrine, Hepato‐Biliary, Pancreatic and Liver Transplant SurgeryTrousseau HospitalToursFrance
| | - Gabriella Pittau
- Centre Hépato‐Biliaire, Hôpital Paul Brousse, Assistance Publique‐Hôpitaux de Paris (AP‐HP)Université Paris SudVillejuifFrance
| | - Marc‐Antoine Allard
- Centre Hépato‐Biliaire, Hôpital Paul Brousse, Assistance Publique‐Hôpitaux de Paris (AP‐HP)Université Paris SudVillejuifFrance
| | - Pierre Pradat
- Clinical Research Centre, Hospices Civils de LyonClaude Bernard Lyon 1 UniversityLyonFrance
| | - Guillaume Rossignol
- Department of Digestive Surgery & Liver Transplantation, Croix‐Rousse Hospital, Hospices Civils de LyonClaude Bernard Lyon 1 UniversityLyonFrance
| | - Jean‐Yves Mabrut
- Department of Digestive Surgery & Liver Transplantation, Croix‐Rousse Hospital, Hospices Civils de LyonClaude Bernard Lyon 1 UniversityLyonFrance
| | - Rutger J. Ploeg
- Nuffield Department of Surgical SciencesUniversity of OxfordOxfordUK
| | - Peter J. Friend
- Nuffield Department of Surgical SciencesUniversity of OxfordOxfordUK
| | - Darius F. Mirza
- Liver Unit, Queen Elizabeth HospitalUniversity Hospitals BirminghamBirminghamUK
| | - Mickaël Lesurtel
- Department of Digestive Surgery & Liver Transplantation, Croix‐Rousse Hospital, Hospices Civils de LyonClaude Bernard Lyon 1 UniversityLyonFrance
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Roll GR, Quintini C, Reich DJ. In quest of the what, when, and where for machine perfusion dynamic liver preservation: Carpe diem! Liver Transpl 2022; 28:1701-1703. [PMID: 35844177 DOI: 10.1002/lt.26546] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 07/11/2022] [Indexed: 01/13/2023]
Affiliation(s)
- Garrett R Roll
- Division of Transplant, Department of Surgery, University of California, San Francisco, California, USA
| | - Cristiano Quintini
- Transplantation Center, Department of Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - David J Reich
- Department of Surgery, Transplant Institute, Drexel University College of Medicine and School of Biomedical Engineering, Philadelphia, Pennsylvania, USA
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Campsen J, Zimmerman MA. Pancreas transplantation following donation after circulatory death. TRANSPLANTATION REPORTS 2022. [DOI: 10.1016/j.tpr.2022.100120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Ramírez-Del Val A, Guarrera J, Porte RJ, Selzner M, Spiro M, Raptis DA, Friend PJ, Nasralla D. Does machine perfusion improve immediate and short-term outcomes by enhancing graft function and recipient recovery after liver transplantation? A systematic review of the literature, meta-analysis and expert panel recommendations. Clin Transplant 2022; 36:e14638. [PMID: 35279883 DOI: 10.1111/ctr.14638] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/28/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Recent evidence supports the use of machine perfusion technologies (MP) for marginal liver grafts. Their effect on enhanced recovery, however, remains uncertain. OBJECTIVES To identify areas in which MP might contribute to an ERAS program and to provide expert panel recommendations. DATA SOURCES Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach. CRD42021237713 RESULTS: Both hypothermic (HMP) and normothermic (NMP) machine perfusion demonstrated significant benefits in preventing postreperfusion syndrome (PRS) (HMP OR .33, .15-.75 CI; NMP OR .51, .29-.90 CI) and early allograft dysfunction (EAD) (HMP OR .51, .35-.75 CI; NMP OR .66, .45-.97 CI), while shortening LOS (HMP MD -3.9; NMP MD -12.41). Only NMP showed a significant decrease in the length of ICU stay (L-ICU) (MD -7.07, -8.76; -5.38 CI), while only HMP diminishes the likelihood of major complications. Normothermic regional perfusion (NRP) reduces EAD (OR .52, .38-.70 CI) and primary nonfunction (PNF) (OR .51, .27-.98 CI) without effect on L-ICU and LOS. CONCLUSIONS The use of HMP decreases PRS and EAD, specifically for marginal grafts. This is supported by a shorter LOS and a lower rate of major postoperative complications (QOE; moderate | Recommendation; Strong). NMP reduces the incidence of PRS and EAD with associated shortening in L-ICU for both DBD and DCD grafts (QOE; moderate | Recommendation; High) This technology also shortens the length of hospital stay (QOE; low | Recommendation; Strong). NRP decreases the likelihood of EAD (QOE; moderate) and the risk of PNF (QOE; low) when compared to both DBD and SRR-DCD grafts preserved in SCS. (Recommendation; Strong).
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Affiliation(s)
| | - James Guarrera
- Division of Liver Transplantation and Hepatobiliary Surgery at Rutgers, New Jersey Medical School, Newark, New Jersey, USA
| | - Robert J Porte
- Department of Surgery, University of Groningen, Groningen, The Netherlands
| | - Markus Selzner
- Department of Abdominal Transplant, Toronto General Hospital, Toronto, Ontario, Canada
| | - Michael Spiro
- Department of Anaesthesia and Intensive Care Medicine, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
| | - Dimitri Aristotle Raptis
- Division of Surgery and Interventional Science, University College London, London, UK.,Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London, UK
| | - Peter J Friend
- Transplant Unit, Churchill Hospital, Oxford University Hospitals, Oxford, UK.,Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - David Nasralla
- Division of Surgery and Interventional Science, University College London, London, UK.,Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London, UK
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Muller X, Rossignol G, Mohkam K, Mabrut JY. Novel strategies in liver graft preservation - The French perspective. J Visc Surg 2022; 159:389-398. [PMID: 36109331 DOI: 10.1016/j.jviscsurg.2022.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Given the increasing graft shortage, the transplant community is forced to use so called marginal liver grafts with a higher susceptibility to ischemia-reperfusion injury. This exposes the recipient to a higher risk of graft failure and post-transplant complications. While static cold storage remains the gold standard in low-risk transplant scenarios, dynamic preservation strategies may allow to improve outcomes after transplantation of marginal liver grafts. Two dynamic preservation strategies, end-ischemic hypothermic oxygenated perfusion (HOPE) and continuous normothermic machine perfusion (cNMP), have been evaluated in randomized clinical trials. The results show improved preservation of liver grafts after cNMP and reduction of post-transplant biliary complications after HOPE. In comparison to cNMP, HOPE has the advantage of requiring less logistics and expertise with the possibility to return to default static cold storage. Both strategies allow to assess graft viability prior to transplantation and may thus contribute to optimizing graft selection and reducing discard rates. The use of dynamic preservation is rapidly increasing in France and results from a national randomized trial on the use of HOPE in marginal grafts will soon be available. Future applications should focus on controlled donation after circulatory death liver grafts, split grafts and graft treatment during perfusion. The final aim of dynamic liver graft preservation is to improve post-transplant outcomes, increase the number of transplanted grafts and allow expansion of transplant indications.
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Affiliation(s)
- X Muller
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France; The Lyon Cancer Research Centre, Inserm U1052 UMR 5286, Lyon, France; ED 340 BMIC, Claude-Bernard Lyon 1 University, 69622 Villeurbanne, France.
| | - G Rossignol
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France; The Lyon Cancer Research Centre, Inserm U1052 UMR 5286, Lyon, France; ED 340 BMIC, Claude-Bernard Lyon 1 University, 69622 Villeurbanne, France; Department of Pediatric Surgery and Liver Transplantation, Femme-Mère-Enfant University Hospital, Hospices Civils de Lyon, Lyon, France
| | - K Mohkam
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France; The Lyon Cancer Research Centre, Inserm U1052 UMR 5286, Lyon, France; Department of Pediatric Surgery and Liver Transplantation, Femme-Mère-Enfant University Hospital, Hospices Civils de Lyon, Lyon, France
| | - J Y Mabrut
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France; The Lyon Cancer Research Centre, Inserm U1052 UMR 5286, Lyon, France
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Le Dorze M, Martouzet S, Cassiani-Ingoni E, Roussin F, Mebazaa A, Morin L, Kentish-Barnes N. "A Delicate balance"-Perceptions and Experiences of ICU Physicians and Nurses Regarding Controlled Donation After Circulatory Death. A Qualitative Study. Transpl Int 2022; 35:10648. [PMID: 36148004 PMCID: PMC9485469 DOI: 10.3389/ti.2022.10648] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 08/23/2022] [Indexed: 11/13/2022]
Abstract
Controlled donation after circulatory death (cDCD) is considered by many as a potential response to the scarcity of donor organs. However, healthcare professionals may feel uncomfortable as end-of-life care and organ donation overlap in cDCD, creating a potential barrier to its development. The aim of this qualitative study was to gain insight on the perceptions and experiences of intensive care units (ICU) physicians and nurses regarding cDCD. We used thematic analysis of in-depth semi-structured interviews and 6-month field observation in a large teaching hospital. 17 staff members (8 physicians and 9 nurses) participated in the study. Analysis showed a gap between ethical principles and routine clinical practice, with a delicate balance between end-of-life care and organ donation. This tension arises at three critical moments: during the decision-making process leading to the withdrawal of life-sustaining treatments (LST), during the period between the decision to withdraw LST and its actual implementation, and during the dying and death process. Our findings shed light on the strategies developed by healthcare professionals to solve these ethical tensions and to cope with the emotional ambiguities. cDCD implementation in routine practice requires a shared understanding of the tradeoff between end-of-life care and organ donation within ICU.
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Affiliation(s)
- Matthieu Le Dorze
- AP-HP, Hôpital Lariboisière, Department of Anesthesia and Critical Care Medicine, Paris, France
- Université Paris-Saclay, UVSQ, INSERM, CESP, U1018, Villejuif, France
| | - Sara Martouzet
- Université de Tours, EA 7505 Éducation, Éthique et Santé, Tours, France
| | - Etienne Cassiani-Ingoni
- AP-HP, Hôpital Lariboisière, Department of Anesthesia and Critical Care Medicine, Paris, France
| | - France Roussin
- AP-HP, Hôpital Lariboisière, Department of Anesthesia and Critical Care Medicine, Paris, France
| | - Alexandre Mebazaa
- AP-HP, Hôpital Lariboisière, Department of Anesthesia and Critical Care Medicine, Paris, France
- Université de Paris, Inserm, UMRS 942 Mascot, Paris, France
| | - Lucas Morin
- INSERM CIC 1431, University Hospital of Besançon, Besançon, France
| | - Nancy Kentish-Barnes
- AP-HP, Saint Louis University Hospital, Famiréa Research Group, Medical Intensive Care Unit, Paris, France
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45
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Widmer J, Eden J, Carvalho MF, Dutkowski P, Schlegel A. Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain? J Clin Med 2022; 11:5218. [PMID: 36079148 PMCID: PMC9457017 DOI: 10.3390/jcm11175218] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 08/30/2022] [Indexed: 11/28/2022] Open
Abstract
Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques-dissimilar to SCS-mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted.
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Affiliation(s)
- Jeannette Widmer
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, 50139 Florence, Italy
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Andrea Schlegel
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
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Parente A, Flores Carvalho M, Eden J, Dutkowski P, Schlegel A. Mitochondria and Cancer Recurrence after Liver Transplantation-What Is the Benefit of Machine Perfusion? Int J Mol Sci 2022; 23:9747. [PMID: 36077144 PMCID: PMC9456431 DOI: 10.3390/ijms23179747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/23/2022] [Accepted: 08/24/2022] [Indexed: 11/16/2022] Open
Abstract
Tumor recurrence after liver transplantation has been linked to multiple factors, including the recipient's tumor burden, donor factors, and ischemia-reperfusion injury (IRI). The increasing number of livers accepted from extended criteria donors has forced the transplant community to push the development of dynamic perfusion strategies. The reason behind this progress is the urgent need to reduce the clinical consequences of IRI. Two concepts appear most beneficial and include either the avoidance of ischemia, e.g., the replacement of cold storage by machine perfusion, or secondly, an endischemic organ improvement through perfusion in the recipient center prior to implantation. While several concepts, including normothermic perfusion, were found to reduce recipient transaminase levels and early allograft dysfunction, hypothermic oxygenated perfusion also reduced IRI-associated post-transplant complications and costs. With the impact on mitochondrial injury and subsequent less IRI-inflammation, this endischemic perfusion was also found to reduce the recurrence of hepatocellular carcinoma after liver transplantation. Firstly, this article highlights the contributing factors to tumor recurrence, including the surgical and medical tissue trauma and underlying mechanisms of IRI-associated inflammation. Secondly, it focuses on the role of mitochondria and associated interventions to reduce cancer recurrence. Finally, the role of machine perfusion technology as a delivery tool and as an individual treatment is discussed together with the currently available clinical studies.
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Affiliation(s)
- Alessandro Parente
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham B15 2GW, UK
| | - Mauricio Flores Carvalho
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
| | - Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Andrea Schlegel
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zurich, Switzerland
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Liver perfusion strategies: what is best and do ischemia times still matter? Curr Opin Organ Transplant 2022; 27:285-299. [PMID: 35438271 DOI: 10.1097/mot.0000000000000963] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW This review describes recent developments in the field of liver perfusion techniques. RECENT FINDINGS Dynamic preservation techniques are increasingly tested due to the urgent need to improve the overall poor donor utilization. With their exposure to warm ischemia, livers from donors after circulatory death (DCD) transmit additional risk for severe complications after transplantation. Although the superiority of dynamic approaches compared to static-cold-storage is widely accepted, the number of good quality studies remains limited. Most risk factors, particularly donor warm ischemia, and accepted thresholds are inconsistently reported, leading to difficulties to assess the impact of new preservation technologies. Normothermic regional perfusion (NRP) leads to good outcomes after DCD liver transplantation, with however short ischemia times. While randomized controlled trials (RCT) with NRP are lacking, results from the first RCTs with ex-situ perfusion were reported. Hypothermic oxygenated perfusion was shown to protect DCD liver recipients from ischemic cholangiopathy. In contrast, endischemic normothermic perfusion seems to not impact on the development of biliary complications, although this evidence is only available from retrospective studies. SUMMARY Dynamic perfusion strategies impact posttransplant outcomes and are increasingly commissioned in various countries along with more evidence from RCTs. Transparent reporting of risk and utilization with uniform definitions is required to compare the role of different preservation strategies in DCD livers with prolonged ischemia times.
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Gaillard-Le Roux B, Cremer R, de Saint Blanquat L, Beaux J, Blanot S, Bonnin F, Bordet F, Deho A, Dupont S, Klusiewicz A, Lafargue A, Lemains M, Merchaoui Z, Quéré R, Samyn M, Saulnier ML, Temper L, Michel F, Dauger S. Organ donation by Maastricht-III pediatric patients: Recommendations of the Groupe Francophone de Réanimation et Urgences Pédiatriques (GFRUP) and Association des Anesthésistes Réanimateurs Pédiatriques d'Expression Française (ADARPEF) Part I: Ethical considerations and family care. Arch Pediatr 2022; 29:502-508. [DOI: 10.1016/j.arcped.2022.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 05/04/2022] [Accepted: 06/18/2022] [Indexed: 11/27/2022]
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Mora V, Ballesteros MA, Naranjo S, Sánchez L, Suberviola B, Iturbe D, Cimadevilla B, Tello S, Alvarez C, Miñambres E. Lung transplantation from controlled donation after circulatory death using simultaneous abdominal normothermic regional perfusion: A single center experience. Am J Transplant 2022; 22:1852-1860. [PMID: 35390225 DOI: 10.1111/ajt.17057] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 04/04/2022] [Accepted: 04/04/2022] [Indexed: 01/25/2023]
Abstract
Despite the benefits of abdominal normothermic regional perfusion (A-NRP) for abdominal grafts in controlled donation after circulatory death (cDCD), there is limited information on the effect of A-NRP on the quality of the cDCD lungs. We aimed to study the effect of A-NRP in lungs obtained from cDCD and its impact on recipients´ outcomes. This is a study comparing outcomes of lung transplants (LT) from cDCD donors (September 2014 to December 2021) obtained using A-NRP as the abdominal preservation method. As controls, all lung recipients transplanted from donors after brain death (DBD) were considered. The primary outcomes were lung recipient 3-month, 1-year, and 5-year survival. A total of 269 LT were performed (60 cDCD and 209 DBD). There was no difference in survival at 3 months (98.3% cDCD vs. 93.7% DBD), 1 year (90.9% vs. 87.2%), and 5 years (68.7% vs. 69%). LT from the cDCD group had a higher rate of primary graft dysfunction grade 3 at 72 h (10% vs. 3.4%; p < .001). This is the largest experience ever reported with the use of A-NRP combined with lung retrieval in cDCD donors. This combined method is safe for lung grafts presenting short-term survival outcomes equivalent to those transplanted through DBD.
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Affiliation(s)
- Victor Mora
- Service of Neumology, Lung Transplantation Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Maria Angeles Ballesteros
- Transplant Coordination Unit & Service of Intensive Care, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Sara Naranjo
- Service of Thoracic Surgery, Lung Transplantation Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Laura Sánchez
- Service of Thoracic Surgery, Lung Transplantation Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Borja Suberviola
- Transplant Coordination Unit & Service of Intensive Care, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - David Iturbe
- Service of Neumology, Lung Transplantation Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Bonifacio Cimadevilla
- Service of Anesthesia, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Sandra Tello
- Service of Neumology, Lung Transplantation Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Carlos Alvarez
- Service of Thoracic Surgery, Lung Transplantation Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Eduardo Miñambres
- Transplant Coordination Unit & Service of Intensive Care, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.,School of Medicine, University of Cantabria, Santander, Spain
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Le Dorze M, Gaillard Le Roux B, Audibert G, Quéré R, Muller L, Lavoué S, Venhard JC, Perrigault PF, Lesieur O. Transferring an ICU Patient at the End of His Life for the Purpose of Organ Donation: Could It Be Considered? Transpl Int 2022; 35:10549. [PMID: 35812161 PMCID: PMC9257584 DOI: 10.3389/ti.2022.10549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/23/2022] [Indexed: 01/03/2023]
Affiliation(s)
- Matthieu Le Dorze
- Ethics Committee of the French Society of Anesthesia and Critical Care Medicine (SFAR), Paris, France
- Department of Anesthesia and Critical Care Medicine, Hôpital Lariboisière AP-HP, Paris, France
- Université Paris-Saclay, UVSQ, INSERM, CESP, U1018, Villejuif, France
| | - Bénédicte Gaillard Le Roux
- Ethics Commission of the French Intensive Care Society (SRLF), Paris, France
- Pediatric Intensive Care Unit, University Hospital, Nantes, France
| | - Gérard Audibert
- Ethics Committee of the French Society of Anesthesia and Critical Care Medicine (SFAR), Paris, France
- Department of Anesthesia and Critical Care Medicine, Nancy University Hospital, University of Lorraine, Nancy, France
| | - Régis Quéré
- Ethics Commission of the French Intensive Care Society (SRLF), Paris, France
- Organ Procurement Organization, Necker University Hospital, Paris, France
| | - Laurent Muller
- Ethics Committee of the French Society of Anesthesia and Critical Care Medicine (SFAR), Paris, France
- Department of Anesthesia and Critical Care Medicine, University Hospital, Nîmes, France
| | - Sylvain Lavoué
- Ethics Commission of the French Intensive Care Society (SRLF), Paris, France
- Intensive Care Unit, University Hospital, Rennes, France
| | - Jean-Christophe Venhard
- Department of Anesthesia and Critical Care Medicine, French Society of Organ Procurement Medicine, University Hospital, Tours, France
| | - Pierre-François Perrigault
- Ethics Committee of the French Society of Anesthesia and Critical Care Medicine (SFAR), Paris, France
- Department of Anesthesia and Critical Care Medicine, University Hospital, Montpellier, France
| | - Olivier Lesieur
- Ethics Commission of the French Intensive Care Society (SRLF), Paris, France
- Intensive Care Unit, General Hospital, La Rochelle, France
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