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用于分期肝切除术的联合肝脏分割和门静脉结扎的动物模型(ALPPS):成就与未来展望

Animal Models for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Achievements and Future Perspectives.

作者信息

Budai Andras, Fulop Andras, Hahn Oszkar, Onody Peter, Kovacs Tibor, Nemeth Tibor, Dunay Miklos, Szijarto Attila

机构信息

Hepato-Pancreatico-Biliary (HPB) Surgical Research Center Hungary, 1st Department of Surgery, Semmelweis University, Budapest, Hungary.

出版信息

Eur Surg Res. 2017;58(3-4):140-157. doi: 10.1159/000453108. Epub 2017 Mar 9.

DOI:10.1159/000453108
PMID:28273656
Abstract

BACKGROUND

Since 2012, Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been standing in the limelight of modern liver surgery and numerous questions have been raised regarding this novel approach. On the one hand, ALPPS has proved to be a valuable method in the treatment of hepatic tumors, while on the other hand, there are many controversies, such as high mortality and morbidity rates. Further surgical research is essential for a better understanding of underlying mechanisms and for enhancing patient safety.

SUMMARY

Until recently, only 8 animal models have been created with the purpose to mimic ALPPS-induced liver regeneration. From these 7 are rodent (6 rat and 1 mouse) models, while only 1 is a large animal model, which uses pigs. In case of rodent models, portal flow deprivation of 75-90% is achieved via portal vein ligation leaving only the right (20-25%) or left median (10-15%) lobes portally perfused, while liver splitting in general is carried out positioned according to the falciform ligament. As for the swine model, the left lateral and medial lobes (70-75% of total liver volume) are portally ligated, and the right lateral lobe (accounting for 20-24% of the parenchyma) is partially resected in order to reach critical liver volume. Each model is capable of reproducing the accelerated liver regeneration seen in human cases. However, all species have significantly different liver anatomy compared with the human anatomic situation, making clinical translation somewhat difficult. Key Messages: Unfortunately, there are no perfect animal models available for ALPPS research. Small animal models are inexpensive and well suited for basic research, but may only provide limited translational potential to humans. Clinically large animal models may provide more relevant data, but currently no suitable one exists.

摘要

背景

自2012年以来,联合肝脏分隔和门静脉结扎分期肝切除术(ALPPS)一直处于现代肝脏手术的聚光灯下,关于这种新方法也引发了众多问题。一方面,ALPPS已被证明是治疗肝脏肿瘤的一种有价值的方法,而另一方面,也存在许多争议,如高死亡率和发病率。进一步的外科研究对于更好地理解潜在机制和提高患者安全性至关重要。

总结

直到最近,仅创建了8个旨在模拟ALPPS诱导的肝再生的动物模型。其中7个是啮齿动物(6只大鼠和1只小鼠)模型,而只有1个是大型动物模型,使用猪。在啮齿动物模型中,通过门静脉结扎实现75 - 90%的门静脉血流阻断,仅留下右侧(20 - 25%)或左中叶(10 - 15%)由门静脉灌注,而一般肝实质离断是根据镰状韧带进行定位。至于猪模型,门静脉结扎左外侧叶和内侧叶(占肝脏总体积的70 - 75%),并部分切除右侧叶(占实质的20 - 24%)以达到临界肝体积。每个模型都能够再现人类病例中所见的加速肝再生。然而,与人类解剖情况相比,所有物种的肝脏解剖结构都有显著差异,这使得临床转化有些困难。关键信息:不幸的是,目前没有适用于ALPPS研究的完美动物模型。小动物模型成本低,非常适合基础研究,但对人类的转化潜力可能有限。临床大型动物模型可能提供更相关的数据,但目前尚无合适的模型。

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