A preliminary study of ALPPS procedure in a rat model

Abstract

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been reported to be a novel surgical technique that provides fast and effective growth of liver remnant. Despite occasional reports on animal studies, the mechanisms of rapid liver regeneration in ALPPS remains unclear. In the present study, we intend to develop a reproducible rat model to mimick ALPPS and to explore the underlying mechanisms. Rats assigned to the portal vein ligation (PVL), left lateral lobe (LLL) resection, transection and sham groups served as controls. Results indicated that the regeneration rate in the remnant liver after ALPPS was two times relative to PVL, whereas rats with transection alone showed minimal volume increase. The expression levels of Ki-67 and PCNA were about ten-fold higher after ALPPS compared with the transection and LLL resection groups, and four-fold higher compared with the PVL group. The levels of TNF-α, IL-6 and HGF in the regenerating liver remnant were about three-fold higher after ALPPS than the controls. There was a more significant activation of NF-κB p65, STAT3 and Yap after ALPPS, suggesting synergistic activation of the pathways by PVL and transection, which might play an important role in liver regeneration after ALPPS.

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

“…The role of inflammatory cytokines was also demonstrated by Yao et al [35], who found increased levels of TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), and HGF (hepatocyte growth factor) after ALPPS upon comparison with the PVL group. Supportive of these findings is a report by Shi et al [36] who found elevated NF-κB (nuclear factor-κ light chain enhancer of activated B cells), p65, STAT3 (signal transducer and activator of transcription 3), and YAP (yes-associated protein) expressions after ALPPS; these mediators have a cardinal role in cell cycle induction and maintenance, and also have strong downstream interplay with the main inflammatory cytokines.…”

“…Their biological properties provide favorable conditions for research by reason of their great regenerative capacity and stress tolerance, making rodents ideal for surgical research. With respect to ALPPS, however, rodents seem to be less ideal for research purposes, although they may provide valuable data for answers to basic research questions as shown in the publications of Schlegel et al [34], Yao et al [35], or Shi et al [36]. On the other hand, certain data collected from rodent research cannot be directly applied to humans owing to the undeniable differences in general physiology.…”

“…a Yao et al [35], Dhar et al [65], and Almau et al [64]. b Schlegel et al [34] and Shi et al [36]. c García-Pérez et al [63].…”

“…Subsequently, various research groups created their own, rat-based ALPPS models with minor changes to the primary concepts of Yao or Schlegel [36,64,65]. …”

RNA-Seq transcriptome profiling in three liver regeneration models in rats: comparative analysis of partial hepatectomy, ALLPS, and PVL

“…Our data revealed that time-dependent factors appear to be the major source of variation in post-injury alterations of gene expression in liver regeneration. Early transcriptomic changes and the upstream regulators after all the procedures included cell cycle associated genes (E2F1, CCND1, FOXM1, TP53, and RB1), transcription factors (Myc, E2F1, TBX2, FOXM1) [23][24][25][26][27][28] , DNA replication regulators (CDKN1A, EZH2, RRM2) 29 , G1/S-transition regulators (CCNB1, CCND1, RABL6) 30 , cytokines and growth factors (CSF2, IL-6, TNF, HGF, VEGF, and EGF) 9,16,31,32 . At the cellular level, this corresponds to the transition from the quiescent G0 phase to active mitosis.…”