Commentary: Quo vadis ex vivo lung perfusion—regionalization or centralization?

Central MessageRegionalization and centralization will both play a role in the future of EVLP.See Article page 164. Regionalization and centralization will both play a role in the future of EVLP. See Article page 164. I read with great interest the article “Human Organ Repair Centers: Fact or Fiction?” published by Dr Keshavjee in the latest issue of the JTCVS Open.1Keshavjee S. Human organ repair centers: fact or fiction?.J Thorac Cardiovasc Surg Open. 2020; 3: 164-168Scopus (6) Google Scholar This work provides a comprehensive summary of the current state of ex vivo lung perfusion (EVLP) and proposes a centralized organizational structure for organ-repair facilities. EVLP is applied by an increasing number of lung transplant programs worldwide, and there is no doubt that this technique will be further exploited. In my opinion, the 2 key applications of EVLP are (1) optimizing organ preservation and thus prolonging preservation time and (2) serving as a platform for organ repair. Limited preservation time remains one of the unsolved problems in clinical lung transplantation. With currently available preservation techniques, lungs can be maintained viable outside the body for only 6 to 8 hours without jeopardizing graft function.2Thabut G. Mal H. Cerrina J. Dartevelle P. Dromer C. Velly J.F. et al.Graft ischemic time and outcome of lung transplantation: a multicenter analysis.Am J Respir Crit Care Med. 2005; 171: 786-791Crossref PubMed Scopus (158) Google Scholar The potential of EVLP to overcome this tight time frame has been highlighted in an analysis from the Toronto group showing that preservation times of >12 hours can be reached safely with EVLP.3Yeung J.C. Krueger T. Yasufuku K. de Perrot M. Pierre A.F. Waddell T.K. et al.Outcomes after transplantation of lungs preserved for more than 12 h: a retrospective study.Lancet Respir Med. 2017; 5: 119-124Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar A fascinating outlook of current limits was given by the Zurich liver transplant team, where preservation times of 1 week were reached by normothermic ex vivo perfusion in a study on human livers.4Eshmuminov D. Becker D. Bautista Borrego L. Hefti M. Schuler M.J. Hagedorn C. et al.An integrated perfusion machine preserves injured human livers for 1 week.Nat Biotechnol. 2020; 38: 189-198Crossref Scopus (141) Google Scholar This certainly raises the question if lung transplantation will eventually become an elective procedure. Standardized perfusion protocols are currently developed aiming to maintain grafts stable for an extended period of time. Using EVLP to prolong organ-preservation times implies that it is done on a regional level, at the site of implantation. The concept of using EVLP as a platform to resuscitate primarily unacceptable grafts opens a whole field of thrilling, new applications. Apart from structural parenchymal changes (ie, emphysema or fibrosis), almost all quality flaws of donor lungs are potentially reversible. This, however, requires an individual approach according to the needs of each organ: grafts that are primarily edematous might be treated by high-oncotic perfusion solutions,5Nilsson T. Hansson C. Wallinder A. Malm C.J. Silverborn M. Ricksten S.E. et al.Hemofiltration in ex vivo lung perfusion—a study in experimentally induced pulmonary edema.J Thorac Cardiovasc Surg. 2016; 151: 570-575.e1Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar organs with signs of pneumonia might need high-dose antibiotic treatment,6Nakajima D. Cypel M. Bonato R. Machuca T.N. Iskender I. Hashimoto K. et al.Ex vivo perfusion treatment of infection in human donor lungs.Am J Transplant. 2016; 16: 1229-1237Crossref PubMed Scopus (103) Google Scholar hepatitis C virus–positive grafts could be sterilized during EVLP,7Galasso M. Feld J.J. Watanabe Y. Pipkin M. Summers C. Ali A. et al.Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion.Nat Commun. 2019; 10: 481Crossref PubMed Scopus (61) Google Scholar pulmonary embolism could be treated by fibrinolytic drugs,8Inci I. Yamada Y. Hillinger S. Jungraithmayr W. Trinkwitz M. Weder W. Successful lung transplantation after donor lung reconditioning with urokinase in ex vivo lung perfusion system.Ann Thorac Surg. 2014; 98: 1837-1838Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar et cetera. I foresee that only a limited number of high-volume facilities will develop sufficient expertise in lung repair and offer it to a network of surrounding referral centers. Such a centralization will facilitate smaller lung transplant programs to use marginal grafts and expand their local donor pool without the need of spending significant resources in maintaining their own organ-repair platform. A prerequisite for a centralized organ-repair concept is a clear definition, which quality criteria a graft has to fulfill after EVLP. These criteria have to go beyond mere reporting of Pao2/Fio2 ratios but include real-time testing of the grade of parenchymal damage as well as the true functional reserve of an organ. In conclusion, I believe that the future of EVLP will be characterized by both—regionalization and centralization. Plug-and-play perfusion machines using highly standardized perfusion protocols will improve organ preservation on a regional level. The requirements for an organ repair facility, however, can only be provided by a supra-regional, centralized approach. Human organ repair centers: Fact or fiction?JTCVS OpenVol. 3PreviewFeature Editor Note—Although lung transplantation continues to evolve with the refinement of surgical techniques and improvements in organ preservation, there continues to be a critical shortage of donor lungs available, and a substantial number of donor lungs are discarded due to questionable quality. The University of Toronto group has published extensively on the use of ex vivo lung perfusion (EVLP) to evaluate marginal donor lungs, demonstrating that many of these lungs can be successfully transplanted. Full-Text PDF Open Access

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