A preliminary study of ALPPS procedure in a rat model

Area of Science:

• Hepatobiliary Surgery
• Regenerative Medicine
• Surgical Oncology

Background:

• Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a surgical innovation promoting rapid liver remnant growth.
• The precise mechanisms driving this accelerated liver regeneration remain incompletely understood.
• Existing animal models do not fully replicate the conditions or outcomes of ALPPS.

Purpose of the Study:

• To establish a reproducible rat model simulating the ALPPS procedure.
• To investigate the molecular mechanisms underlying rapid liver regeneration post-ALPPS.
• To compare regeneration rates and molecular markers between ALPPS and control surgical groups.

Main Methods:

• Development of a rat model mimicking ALPPS, with control groups including portal vein ligation (PVL), left lateral lobe (LLL) resection, and transection.
• Quantification of liver remnant regeneration rates using volumetric analysis.
• Assessment of cell proliferation markers (Ki-67, PCNA) and inflammatory cytokines (TNF-α, IL-6, HGF) via expression analysis.
• Evaluation of key signaling pathway activation (NF-κB p65, STAT3, Yap) through molecular assays.

Main Results:

• The ALPPS rat model demonstrated a two-fold higher regeneration rate compared to PVL alone.
• Cell proliferation markers (Ki-67, PCNA) were significantly elevated (approx. 10-fold) in the ALPPS group versus transection/LLL resection groups.
• Levels of TNF-α, IL-6, and HGF were approximately three-fold higher in the regenerating liver remnant after ALPPS.
• Synergistic activation of NF-κB p65, STAT3, and Yap pathways was observed post-ALPPS.

Conclusions:

• The developed rat model effectively mimics ALPPS and facilitates the study of liver regeneration mechanisms.
• Combined portal vein ligation and transection in ALPPS induce robust liver regeneration.
• Activation of NF-κB, STAT3, and Yap pathways plays a critical role in mediating the rapid liver growth observed in ALPPS.