The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham B15 2GW, UK.
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy.
Int J Mol Sci. 2022 Aug 28;23(17):9747. doi: 10.3390/ijms23179747.
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.
肝移植后肿瘤复发与多种因素有关,包括受者肿瘤负荷、供者因素和缺血再灌注损伤(IRI)。接受扩展标准供体的肝脏数量不断增加,迫使移植界推动动态灌注策略的发展。这一进展的背后是迫切需要减少 IRI 的临床后果。有两个概念似乎最有益,包括避免缺血,例如用机器灌注代替冷保存,或者通过在受者中心进行缺血前灌注来改善缺血器官。虽然包括常温灌注在内的几种概念被发现可以降低受体转氨酶水平和早期移植物功能障碍,但低温氧合灌注也降低了与 IRI 相关的移植后并发症和成本。由于对线粒体损伤的影响以及随后的 IRI 炎症减少,这种缺血前灌注也被发现可以降低肝移植后肝细胞癌的复发。首先,本文强调了导致肿瘤复发的因素,包括手术和医学组织创伤以及与 IRI 相关炎症的潜在机制。其次,它重点介绍了线粒体及其相关干预措施在减少癌症复发方面的作用。最后,讨论了机器灌注技术作为一种输送工具和单独治疗的作用,以及目前可用的临床研究。