Protective effect of peroxisome proliferator-activated receptor- in regulating the early inflammation response to extended hepatectomy from a comparative transcriptomic analysis

The regulation mechanism of small-for-size syndrome remains unclear. Thus, we aimed to analyze the molecular profiles following extended hepatectomy and identify the therapeutic target. Major hepatectomy and extended hepatectomy were performed in the rat model, and the remnant livers were obtained dynamically for the high-throughput transcriptome analysis to identify the differentially expressed genes (DEGs). The general framework for weighted gene co-expression network analysis (WGCNA) was employed to explore the expression patterns of DEGs. As result, WGCNA identified 10 distinct gene co-expression modules according to the correlation between module eigengene and different postoperative time-points. The magenta module and the lightcyan module were found positively correlated with not extended hepatectomy but major hepatectomy. In the lightcyan module, peroxisome proliferator-activated receptor- (PPAR) was selected and verified the down-regulation in the remnant liver following extended hepatectomy in rats and humans. Besides, administration of PPAR agonist attenuated hepatic inflammation injury while PPAR antagonist increased liver inflammation injury after extended hepatectomy in rats, marked by the significantly changed aminotransferases, tumor necrosis factor- and interleukin-6 levels in the plasm, and histological Suzuki criteria. Consequently, DEGs and their molecular profiles after extended hepatectomy were identified, and PPAR might be a potential therapy target for small-for-size syndrome.

Critical Role of LSEC in Post-Hepatectomy Liver Regeneration and Failure

Liver sinusoids are lined by liver sinusoidal endothelial cells (LSEC), which represent approximately 15 to 20% of the liver cells, but only 3% of the total liver volume. LSEC have unique functions, such as fluid filtration, blood vessel tone modulation, blood clotting, inflammatory cell recruitment, and metabolite and hormone trafficking. Different subtypes of liver endothelial cells are also known to control liver zonation and hepatocyte function. Here, we have reviewed the origin of LSEC, the different subtypes identified in the liver, as well as their renewal during homeostasis. The liver has the exceptional ability to regenerate from small remnants. The past decades have seen increasing awareness in the role of non-parenchymal cells in liver regeneration despite not being the most represented population. While a lot of knowledge has emerged, clarification is needed regarding the role of LSEC in sensing shear stress and on their participation in the inductive phase of regeneration by priming the hepatocytes and delivering mitogenic factors. It is also unclear if bone marrow-derived LSEC participate in the proliferative phase of liver regeneration. Similarly, data are scarce as to LSEC having a role in the termination phase of the regeneration process. Here, we review what is known about the interaction between LSEC and other liver cells during the different phases of liver regeneration. We next explain extended hepatectomy and small liver transplantation, which lead to “small for size syndrome” (SFSS), a lethal liver failure. SFSS is linked to endothelial denudation, necrosis, and lobular disturbance. Using the knowledge learned from partial hepatectomy studies on LSEC, we expose several techniques that are, or could be, used to avoid the “small for size syndrome” after extended hepatectomy or small liver transplantation.

Eight-Year Survival Following Left Hepatic Trisectionectomy With Combined Hepatic Artery And Portal Vein Resection For Advanced Perihilar Cholangiocarcinoma

We report the case of a patient with exceptional survival over 8 years after left trisectionectomy combined with portal vein and hepatic artery resection and reconstruction for advanced perihilar cholangiocarcinoma. Such extended hepatectomy with vascular resection is the only way to obtain free tumor margin. It can be performed with acceptable morbidity and mortality and it is the only hope to prolong survival.

Towards the Study of Liver Failure: Protocol for a 90% Extended Hepatectomy in Mice

Studies have shown that extended hepatectomy mimics post-hepatectomy liver failure (PHLF) and could also be used to study other small-for-flow syndromes. Extended hepatectomy can be defined as the removal of more than 70% of liver volume. At the molecular level, there seems to be a delayed entrance to the cell cycle, and thus liver dysfunction ensues. Therefore, there is an imperious need to study the mechanisms of such delay to understand how it can be regulated. While the classical 70% hepatectomy model to study liver regeneration has been previously described thoroughly, there are no protocols describing the surgical procedure for a 90% extended hepatectomy (90% EHx). Therefore, we here describe a detailed and reproducible protocol for such model, defining specific aspects that must be considered as well as the most common complications and troubleshooting strategies.

A fast and easy-to-learn technique for liver resection in a porcine model

Objective Despite the recent advances in surgical techniques and perioperative care, liver resection (especially extended hepatectomy) is still a high-risk procedure with considerable morbidity and mortality. Experimental large animal models are the best option for studies in this regard. The present study was performed to present an easy-to-learn, fast, and multipurpose model of liver resection in a porcine model. Method Stepwise liver resections (resection of segments II/III, IVa/IVb, and VIII/IV) were performed in eight pigs with intraoperative monitoring of hemodynamic parameters. The technical aspects, tips, and tricks of this method are explained in detail. Results Based on the specific anatomical characteristics of the porcine liver, all resection types including segmental resection, hemihepatectomy, and extended hepatectomy could be performed in one animal in an easy-to-learn and fast technique. All animals were hemodynamically stable following stepwise liver resection. Conclusion Stepwise liver resection using stapler in a porcine model is a fast and easy-to-learn method with which junior staff and research fellows can perform liver resection up to extended hepatectomy under stable conditions.