Exploring the Enhanced Liver Regeneration Patterns Following ALPPS Versus Selective Portal Vein Ligation in an Experimental Model

IF 1.5 Q4 ONCOLOGY

Cancer reports Pub Date : 2025-06-04 DOI:10.1002/cnr2.70221

Dora Krisztina Tihanyi, Attila Szijarto, Andras Fulop, Decan Jiang, Lisa Ernst, Franziska Alexandra Meister, Christian Bleilevens, Alexander Theissen, Henrik Nienhüser, Deniz Uluk, Georg Lurje, Mehrabi Arianeb, Rene H. Tolba, Zoltan Czigany

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Abstract

Background

Associating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) and selective PV embolization (PVE) are important clinical strategies in liver surgery. Even though it has been demonstrated that ALPPS induces a more rapid and expressed hypertrophy than PVL/PVE, this phenomenon is still not well understood.

Aim

In the present study, we aimed to characterize enhanced regeneration patterns in a rat model.

Methods

Male Wistar rats were used (n = 84; 220–250 g). Selective PVL and ALPPS were achieved using microsurgical techniques (RML-regenerating/LML-non-regenerating). Parameters of liver regeneration, microcirculation, hepatocyte morphology, hepatocellular injury, and activation status of certain protein kinases involved in liver regeneration were investigated.

Results

Right median lobe (RMLs) in the ALPPS group exhibited a more significant and rapid hypertrophy compared to PVL (regeneration ratio, 1.669 ± 0.155 vs. 1.980 ± 0.189, p = 0.009, PVL vs. ALPPS). ALPPS led to a more prominent hepatocellular injury. Hypertrophy was associated with increased microcirculation of the RML and a prominent increase of hepatocellular size (300.43 ± 31.92 μm² vs. 374.48 ± 58.34 μm², PVL vs. ALPPS) and morphology. There was an early pAkt/Akt activation after surgery which was significantly higher in ALPPS (5 ± 2 vs. 9.7 ± 3 RQ-fold-change, p = 0.0087, PVL vs. ALPPS).

Conclusions

Our results suggest that the enhanced regeneration in ALPPS is associated with characteristic changes in liver microcirculation, cell division, hepatocyte morphology, and activation of pAkt/Akt.

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在实验模型中探讨ALPPS与选择性门静脉结扎后肝脏再生模式的增强

背景联合肝分区和门静脉结扎（PVL）进行分期肝切除术（ALPPS）和选择性门静脉栓塞（PVE）是肝脏外科手术中重要的临床策略。尽管已经证明ALPPS诱导比PVL/PVE更快和表达的肥厚，但这一现象仍未得到很好的理解。目的在本研究中，我们旨在描述大鼠模型中增强的再生模式。方法采用雄性Wistar大鼠(n = 84；220 - 250克)。采用显微外科技术（rml -再生/ lml -非再生）实现选择性PVL和ALPPS。研究了肝再生、微循环、肝细胞形态、肝细胞损伤及参与肝再生的某些蛋白激酶的激活状态。结果与PVL组相比，ALPPS组右正中叶（RMLs）出现了更明显、更快速的肥厚（再生比，1.669±0.155比1.980±0.189,p = 0.009, PVL vs. ALPPS）。ALPPS导致肝细胞损伤更为突出。肥厚与RML微循环增加、肝细胞大小（300.43±31.92 μm2 vs 374.48±58.34 μm2, PVL vs ALPPS）和形态显著增加有关。术后早期的pAkt/Akt激活在ALPPS患者中显著升高（5±2比9.7±3 rq -fold change, p = 0.0087, PVL vs. ALPPS）。结论ALPPS再生增强与肝脏微循环、细胞分裂、肝细胞形态和pAkt/Akt活化的特征性变化有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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