氧化应激反应在边缘供肝肝移植缺血-再灌注损伤中的作用研究进展

常见的边缘供肝主要包括脂肪变性供肝、高龄供肝、小体积供肝、心脏死亡器官捐献(DCD)供肝等。边缘供肝的应用可在一定程度上解决供肝数量严重短缺的问题,但边缘供肝面临着缺血-再灌注损伤(IRI)的难题,且IRI程度相比正常供肝更加严重,是导致移植失败的重要原因,其中氧化应激反应又是引起边缘供肝IRI的重要因素。因此如何减少氧化应激反应及解决边缘供肝IRI的难题成为临床研究的热点问题。活性氧簇(ROS)介导的氧化应激反应贯穿IRI整个过程,本文就氧化应激反应在边缘供肝肝移植IRI中的作用及以ROS为靶点的防治进行综述,以期为临床提供参考。     

机械灌注在公民逝世后器官捐献供肾质量维护方面的应用研究进展

公民逝世后器官捐献目前已成为我国器官捐献的主要来源,但是由于供者质量的复杂性,扩大标准供者(ECD)供肾占比增加,从而对供肾的可利用性以及肾移植受者术后的长期预后造成很大的影响.加强供肾质量的维护与评估,对于改善供肾质量、增加供肾获取与利用、改善受者和移植肾长期存活具有重要意义.机械灌注保存作为器官保存的重要方式之一,...     

体外膜肺氧合在心脏死亡器官捐献供体肝移植中的应用进展

供肝短缺已经成为制约肝移植发展的重要因素,心脏死亡器官捐献(DCD)供体是扩大供体池的一个重要来源。应用体外膜肺氧合(ECMO)技术可提高DCD供肝的质量,增加器官捐献供体池,改善肝移植受体的预后。本文综述了ECMO对DCD供体器官支持的基本原理和操作技术、ECMO用于DCD供体肝移植的研究进展及存在的问题,提示ECMO在我国DCD供体肝移植中具备较大的发展潜力和应用前景。     

心脏死亡器官捐献供肝获取术的临床配合及管理

目的总结心脏死亡器官捐献(DCD)供肝获取术的临床配合和管理经验。方法回顾性分析113例供体器官获取手术的临床资料,总结手术配合体会。结果术前准备做好手术人员和常用器械准备、灌注管路和液体的准备和术中药品的准备。手术配合包括器官获取前工作、器官获取、分离供体肝、肾。所有器官获取过程顺利,后续完成102例经典原位肝移植手术。其中4例由于供肝质量问题弃用,7例供肝分配至其他移植中心。结论对于DCD供肝获取术,良好的手术配合及管理有助于提高手术成功率。     

公民逝世后器官捐献供肝肝移植:我国儿童肝移植的新出路

我国是先天性胆道疾病和肝脏疾病的高发国家,部分患儿发展为终末期肝病,因此,儿童肝移植在我国有很大的发展空间。儿童肝移植的供肝类型主要包括尸体全肝、尸体减体积供肝、尸体劈离式供肝和活体供肝。在我国,儿童肝移植以活体肝移植为主,但存在伦理学争议,且不易找到合适的供体,严重限制了我国儿童肝移植的发展。近年我国公民逝世后器官捐献供肝数量不断增加,劈离式肝移植自2010年起得到迅速增长,活体供肝所占比例也随之降低。随着我国公民逝世后器官捐献事业的发展,公民逝世后器官捐献供肝将取代活体供肝成为我国儿童肝移植主要供肝来源。     

肝移植供肝的保存

保持供体器官离体后的活力,对于移植后器官迅速恢复功能和存活是十分重要的.迄今为止,肝移植供肝的静态低温保存仍是普遍采用的方法.虽然这种方法简单而且有效,但是随着供体老年化、边缘化和心跳停止供肝数量的增加,导致供肝的质量日益恶化,静态低温保存能否继续保持供肝活力令人怀疑.本综述介绍供肝保存及器官保存液的发展历史及最新进展,包括低温机器灌注.尽管低温机器灌注可能优于静态低温保存,但是供肝仍然存在低温相关损伤.因此,最近已有科研机构开始重视常温机器灌注的研究,并有望成为肝脏移植保存的新方法.     

脂肪变性供肝在肝移植中的应用现状与进展

肝移植是终末期肝病最有效的治疗措施,但器官供需的严重失衡已经成为制约肝移植进一步发展的关键因素.因此,如何合理使用边缘性供肝已成为肝移植临床的重点.常见的边缘性供肝有脂肪变性供肝、乙肝表面抗原阳性肝脏、超过60岁的高龄供者捐献的肝脏、冷缺血时间>14 h的肝脏、心脏死亡器官捐献(donation-after-circu...     

公民心死亡器官捐献肝移植

目的 总结公民心死亡器官捐献肝移植的临床经验.方法 回顾性分析2006年7月至2011年5月广州军区广州总医院施行的20例公民心死亡器官捐献肝移植供受者的临床资料.脑心双死亡器官捐献(DBCD)供者通过体外膜肺氧合技术(ECMO)避免热缺血,M-Ⅲ供者不采用ECMO,待心跳停止5 min后实施肝脏获取手术.受者均采用原位肝移植术,其中17例行胆管端端吻合,3例行胆肠吻合.所有受者获定期随访.采用Kaplan-Meier法绘制生存曲线.结果 20例供者中M-Ⅲ占10％( 2/20),DBCD占90％ (18/20).20例受者均顺利完成手术,平均手术时间、无肝期、术中出血量和术后ICU时间分别为(6.2±2.7)h、(54±13) min、(2305±1311)ml和(44±35)h.全组无手术死亡,术后肝功能恢复满意,无原发性肝脏无功能或移植肝功能恢复延迟;术后1个月内1例受者因脓毒血症死亡,1例因肺部感染死亡,其余18例受者长期生存,最长生存时间为58个月.结论 公民心死亡器官捐献是现阶段我国可以应用的供肝获取方法,其中以DBCD为主要类型;建立科学的心死亡器官捐献肝移植流程,合理使用ECMO等保护供肝质量措施,对我国公民死亡器官捐献工作有着积极的作用.     

代谢组学在心脏死亡器官捐献供肝评估中的应用

肝移植技术在国内日益普及,但仍然面临着供肝严重短缺的困境。心脏死亡器官捐献(DCD)是我国目前供肝的主要来源,其供肝质量的评估方法仍亟待完善。近年新兴的代谢组学研究方法,为移植器官质量的评估提供了一个崭新的角度。本文主要综述了目前国内器官捐献的现状,介绍了代谢组学研究的产生和进展及其在肝移植尤其是供肝质量评估中的应用前景。     

国外捐献器官获取质量管理与控制进展

器官移植是二十世纪以来有效挽救终末期器官衰竭患者生命的一项突破性技术,显著改善了患者生存质量。器官捐献作为器官移植的重要来源,提升捐献器官获取质量是促进捐献器官转化、改善器官移植预后的关键。美国、西班牙等国家在捐献器官获取质量管理与控制方面提出了系列政策和标准,并取得了积极成果。本文通过探讨医疗质量管理与控制有关概念、国际捐献器官获取质量管理先进策略及模式,研究器官获取组织、捐献者、捐献器官质控举措,以期为形成具有“中国特色”的捐献器官获取质量管理与控制体系、推进捐献器官获取高速度高质量发展提供参考。     

常温局部灌注在受控心脏死亡肝移植供体中的应用

目前全球器官移植领域所面临的仍是供体短缺的主要问题。由于受体需求量和标准供体的数量的严重不平衡，外科医生们将目光转移到心脏死亡供体（DCD）。相比于脑死亡供体（DBD），DCD面临的主要问题是经历更长的热缺血时间（WIT），以致患者术后并发症发生率增加，尤其是胆道并发症。受控心脏死亡供体（cDCD）是指在符合患者或家属意愿的情况下有计划地退出维持生命的治疗，在一段“无接触”时间后（通常为5 min），宣布患者大脑循环永久缺失，同时快速进行器官恢复。由于使用常规器官保存方法保存的DCD移植物的移植效果不尽如人意，近年来，常温灌注技术所展现出的优势在移植过程中愈发明显，逐渐引起外科医生和科学家们的关注。与活体肝移植以及DBD肝移植不同，DCD在宣布死亡前无法取出移植物。而在常温局部灌注（NRP）中，外科医生们能够在宣布死亡后阻断流向大脑的血液，并通过体外膜氧合启动器官的热灌注，在供体体内恢复供体肝脏的功能，使肝脏产生胆汁并清除乳酸。这一过程为供体肝脏离开供体和移植前的各项指标监测和优化提供宝贵时间。目前已有多项临床研究表明，NRP作为一种原位器官修复技术能够使cDCD供体肝脏的移植效果与DBD供体相近。另外，一些研究者还开发了多种灌注技术的联合应用，包括NRP与机器灌注（MP）以及双低温氧合机灌注（D-HOPE）的联合使用，均展现出良好的移植效果，为肝移植供体保存提供更多可能性。虽然许多学者认为NRP是一种获取更多高质量器官的保存方法，但有研究者质疑该技术的伦理问题。他们认为该技术违背死亡捐赠规则，NRP灌注程序中所涉及的操作可能导致患者的死亡，因此，确保患者的循环以及呼吸的永久性不可恢复状态以及在NRP期间确保脑部循环的缺失尤其重要。鉴于NRP在移植领域的重要性，笔者对NRP技术在cDCD中的应用进行归纳总结。     

Organ transplantation is getting back its “true” luster in China

Although a great success has been made in the field of organ transplantation in China, the practice of organ donation from executed prisoners has long been rebuked by the international transplant community. The “boycott” attitude of western countries has stifled the development of transplant science and medicine in China. With the efforts of the Chinese government and transplant community, a voluntary organ donation system has been successfully established. The medical authorities have committed that the practice of using organs from executed prisoners will be abandoned in the near future. It is time for a big hug from the international transplant community to its Chinese partner. And it is time for a rapid development of organ transplantation in China.     

The utility of extended criteria donor organs in severely ill liver transplant recipients

Organ shortage in liver transplantation has led the transplant community to expand the donor organ pool and reduce waiting list mortality by using so-called marginal donor or extended criteria donor (ECD) livers. The exact impact of these criteria on graft function and recipient survival are still under investigation. Most reports, however, show a clear correlation between organ quality and the posttransplant outcome. The role of ECD liver transplantation for severely ill recipients with high model for end stage liver disease (MELD) scores needs further clarification since transplant surgeons tend to allocate these grafts to more stable patients with lower MELD scores. Especially in the setting of ECD liver transplantation, strategies to improve graft quality and mitigate preservation and reperfusion injury may prove beneficial and play an important role in the future.     

数据之美——聚焦全球器官捐献发展趋势

器官移植术是20世纪出现的针对器官功能衰竭的最有效治疗方法，每年拯救全球超过12万例患者。但供器官短缺的现状，与器官移植技术和辅助药物的发展不匹配，制约了器官移植事业的发展。我国自2015年起已成为全球器官捐献和移植大国之一，2017年公民逝世后器官捐献数量超过5 000例，占全球捐献总量的15%以上。黄洁夫教授总结的器官捐献与移植"中国模式"得到了世界卫生组织、国际移植界的高度重视和充分肯定。本文通过整理全球及各国的器官捐献与移植数据，剖析全球现状与发展趋势，进一步探索我国公民器官捐献的影响因素并提出针对性的应对策略，以期实现我国器官捐献和移植的"自给自足"。     

Impact of Machine Perfusion Preservation of Liver Grafts From Donation After Cardiac Death

Because of the critical shortage of deceased donor grafts, using a donation after cardiac death (DCD) donor is an important resource. However, the ischemic damage of those DCD grafts jeopardizes organ viability during cold storage. Maintaining organ viability after donation until transplantation is important for optimal graft function and survival. This review describes the effective preservation in transplantation for DCD livers. Concepts and development of machine perfusion for DCD liver grafts to reduce ischemia/reperfusion injury are discussed. Despite the fact that hypothermic machine perfusion might be superior to static cold preservation, DCD livers are exposed to hypothermia-induced damage. Recently, some groups introduced the beneficial effects of normothermic or subnormothermic machine perfusion in DCD liver preservation and transplantation.     

多方协作，全民参与，全面推进我国人体器官捐献体系建设

我国人体器官移植事业逐渐发展的同时也面临诸多问题与挑战,器官短缺严重阻碍着我国器官移植事业的发展。要摆脱人体器官移植工作面临的困境,在加强监管的同时,需从根本上解决器官来源问题,唯一途径就是建立既符合国际社会广泛认可的伦理学原则,又切合我国国情的人体器官捐献体系。为此,中华人民共和国国家卫生和计划生育委员会（原卫生部）委托中国红十字会总会开展人体器官捐献相关工作,并出台配套政策措施推动这项工作顺利开展。在各方的共同努力下,我国人体器官捐献体系初具规模,工作成绩显著。今后,只有多方协作．全民参与,才能全面推进我国人体器官捐献体系建设,开创我国人体器官捐献工作的新局面,使我国的人体器官移植事业再上一个新台阶,为世界器官移植事业做出中国应有的贡献。     

Abdominal Transplant Surgery and Transplant Coordination University Hospitals Leuven 1997–2007: an Overview

The transplant surgery and transplant coordination department was created in 1997 to meet up with the demand of the growing abdominal transplant surgery and organ procurement activity at the University Hospitals in Leuven. Since then, the procurement activity has increased and is currently distributed within the University Hospital Gasthuisberg and a network of ~25 collaborative hospitals. The profile of the donors has changed with older donors and more co-morbidity factors (obesity, hypertension, etc.). This donor activity represents ~30% of the national donor pool. Over the last 10 years, more than 1100 kidneys, more than 500 livers, ~50 pancreas, and 5 intestines have been transplanted in both adults and children. One year survival equal to-or exceeding 90% has been achieved for all abdominal organs and this compares favorably with international registries. More than 40 multi-visceral transplants {liver in combination with abdominal (kidney, pancreas, intestine) or thoracic (heart, double lung, heart-lung) organs} have been performed with results equivalent to isolated liver transplants and very little immunological graft loss (probably due to the immunoprotective effect of the liver). A live donation program was started for the kidney (40 cases) and for the liver (10 cases) in adults and children and no surgical graft loss has been seen so far. Introduction of new machine perfusion systems (and development of donor protocols) has made it possible to restart a non-heart-beating donor program for kidney transplantation. Experimental demonstration that livers tolerate short periods of warm ischemia has also allowed to start liver transplantation from non-heart-beating donors. In the future, machine perfusion of livers, viability testing, and biological modulation are likely to widen the use of marginal livers for transplantation and improve the results. An immunomodulatory protocol proven in the lab to induce the development of regulatory T cells has been applied clinically to 5 consecutive intestinal transplants. All 5 - at the time of writing - have been rejection-free and have achieved nutritional independence. Continuous research and development is warranted to increase the organ donor pool (currently the solely limiting factor of transplantation) and to optimize long-term graft and patient outcome.     

A Novel Oxygenated Machine Perfusion System for Preservation of the Liver

Machine perfusion (MP) is a potential method to increase the donor pool for organ transplantation. However, MP systems for liver grafts remain difficult to use because of organ‐specific demands. Our aim was to test a novel, portable MP system for hypothermic preservation of the liver. A portable, pressure‐regulated, oxygenated MP system designed for kidney preservation was adapted to perfuse liver grafts via the portal vein (PV). Three porcine livers underwent 20 h of hypothermic perfusion using Belzer MP solution. The MP system was assessed for perfusate flow, temperature, venous pressure, and pO₂/pCO₂ during the preservation period. Biochemical and histological parameters were analyzed to determine postpreservation organ damage. Perfusate flow through the PV increased over time from 157 ± 25 mL/min at start to 177 ± 25 mL/min after 20 h. PV pressure remained stable at 13 ± 1 mm Hg. Perfusate temperature increased from 9.7 ± 0.6°C at the start to 11.0 ± 0.0°C after 20 h. Aspartate aminotransferase and lactate dehydrogenase increased from 281 ± 158 and 308 ± 171 U/L after 1 h to 524 ± 163 and 537 ± 168 U/L after 20 h, respectively. Blood gas analysis showed a stable pO₂ of 338 ± 20 mm Hg before perfusion of the liver and 125 ± 14 mm Hg after 1 h perfusion. The pCO₂ increased from 15 ± 5 mm Hg after 1 h to 53 ± 4 mm Hg after 20 h. No histological changes were found after 20 h of MP. This study demonstrated the feasibility of a portable MP system for preservation of the liver and showed that continuous perfusion via the PV can be maintained with an oxygen‐driven pump system without notable preservation damage of the organ.     

Machine Perfusion of Donor Livers for Transplantation: A Proposal for Standardized Nomenclature and Reporting Guidelines

With increasing demand for donor organs for transplantation, machine perfusion (MP) promises to be a beneficial alternative preservation method for donor livers, particularly those considered to be of suboptimal quality, also known as extended criteria donor livers. Over the last decade, numerous studies researching MP of donor livers have been published and incredible advances have been made in both experimental and clinical research in this area. With numerous research groups working on MP, various techniques are being explored, often applying different nomenclature. The objective of this review is to catalog the differences observed in the nomenclature used in the current literature to denote various MP techniques and the manner in which methodology is reported. From this analysis, we propose a standardization of nomenclature on liver MP to maximize consistency and to enable reliable comparison and meta‐analyses of studies. In addition, we propose a standardized set of guidelines for reporting the methodology of future studies on liver MP that will facilitate comparison as well as clinical implementation of liver MP procedures.