Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation, First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Norway.
BJS Open. 2020 Oct;4(5):893-903. doi: 10.1002/bjs5.50322. Epub 2020 Jul 15.
The resection and partial liver segment II/III transplantation with delayed total hepatectomy (RAPID) concept is a novel transplantation technique for removal of non-resectable liver tumours. The aim of this study was to establish a simulated RAPID model to explore the mechanism involved in the liver regeneration.
A RAPID model was created in rats involving cold ischaemia and reperfusion of the selected future liver remnant (FLR), portal vein ligation, followed by resection of the deportalized lobes in a second step. Histology, liver regeneration and inflammatory markers in RAPID-treated rats were compared with those in controls that underwent 70 per cent hepatectomy with the same FLR size. The effects of interleukin (IL) 6 and macrophage polarization on hepatocyte viability were evaluated in an in vitro co-culture system of macrophages and BRL hepatocytes.
The survival rate in RAPID and control hepatectomy groups was 100 per cent. The regeneration rate was higher in the RAPID-treated rats, with higher levels of IL-6 and M1 macrophage polarization (P < 0·050). BRL hepatocytes co-cultured with M1 macrophages showed a higher proliferation rate through activation of the IL-6/signal transducer and activator of transcription 3/extracellular signal-regulated kinase pathway. This enhancement of proliferation was inhibited by tocilizumab or gadolinium trichloride (P < 0·050).
The surgical model provides a simulation of RAPID that can be used to study the liver regeneration profile. Surgical Relevance The mechanisms sustaining liver regeneration are a relevant field of research to reduce the 'small for size' liver syndrome when the future liver remnant is not adequate. Several surgical strategies have been introduced both for liver resection and transplant surgery, mostly related to this issue and to the scarcity of grafts, among these the RAPID concept involving the use of an auxiliary segment II/III donor liver that expands to a sufficient size until a safe second-stage hepatectomy can be performed. Understanding the mechanisms and pitfalls of the liver regeneration profile may help in tailoring surgical strategies and in selecting patients. In this experimental model the authors investigated liver histology, regeneration and inflammatory markers in RAPID-treated rats.
切除和部分肝段 II/III 移植联合延迟性全肝切除术（RAPID）概念是一种用于切除不可切除的肝肿瘤的新型移植技术。本研究旨在建立一个模拟 RAPID 模型，以探索肝再生所涉及的机制。
在大鼠中建立 RAPID 模型，涉及冷缺血和预选未来肝残肝（FLR）再灌注、门静脉结扎，然后在第二步切除去门静脉化的肝叶。RAPID 治疗大鼠的组织学、肝再生和炎症标志物与接受相同 FLR 大小的 70%肝切除术的对照组进行比较。在巨噬细胞和 BRL 肝细胞的体外共培养系统中，评估白细胞介素（IL）6 和巨噬细胞极化对肝细胞活力的影响。
RAPID 和对照组肝切除术的存活率均为 100%。RAPID 治疗组的再生率较高，IL-6 和 M1 巨噬细胞极化水平较高（P<0.050）。与 M1 巨噬细胞共培养的 BRL 肝细胞通过激活 IL-6/信号转导和转录激活因子 3/细胞外信号调节激酶途径显示出更高的增殖率。这种增殖的增强被托珠单抗或三氯化钆抑制（P<0.050）。
该手术模型提供了 RAPID 的模拟，可以用于研究肝再生谱。手术相关性维持肝再生的机制是一个相关的研究领域，可减少未来肝残肝不足时的“小肝综合征”。已经引入了几种手术策略，用于肝切除术和移植手术，主要与这个问题和供体器官的稀缺性有关，其中包括 RAPID 概念，涉及使用辅助的 II/III 段供体肝，直到可以进行安全的第二期肝切除术时，该肝会扩展到足够的大小。了解肝再生谱的机制和陷阱可能有助于制定手术策略和选择患者。在这个实验模型中，作者研究了 RAPID 治疗大鼠的肝组织学、再生和炎症标志物。
