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

在实验模型中探索ALPPS与选择性门静脉结扎术后增强的肝脏再生模式

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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 μm(2) vs. 374.48 ± 58.34 μm(2), 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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