Prognostic value of precise hepatic pedicle dissection in anatomical resection for patients with hepatocellular carcinoma.

The present study aimed to investigate the long-term and perioperative outcomes of precise hepatic pedicle dissection in anatomical resection (precise AR) vs non-anatomical resection (NAR) for hepatocellular carcinoma (HCC) patients.Data from a total of 270 consecutive HCC patients who underwent curative hepatectomy were retrospectively collected. Propensity score matching (PSM) analysis was performed. The long-term outcomes of precise AR and NAR were analyzed using the Kaplan-Meier method and the Cox proportional hazards model.The 1-, 3-, and 5-year overall survival (OS) rates were 90.3%, 76.2%, and 65.7% in the PS-precise AR group, respectively (n = 103); and 88.3%, 70.5%, and 52.0% in the PS-NAR group, respectively (n = 103) (P = .043). The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 83.4%, 63.2%, and 46.0% in the PS-precise AR group, respectively; and 75.7%, 47.4%, and 28.3% in the PS-NAR group, respectively (P = .002). Multivariate analysis showed that ICG-R15, BCLC staging, and microvascular invasion (MVI) were independent risk factors for OS; while tumor size, types of resection, surgical margin, and MVI were independent risk factors for RFS. Subgroup analysis indicated that the RFS rate was significantly better in the PS-precise AR group than in the PS-NAR group for patients with MVI and tumor size ≤5 cm.After PSM, precise hepatic pedicle dissection in AR significantly improved the recurrence-free survival rate of solitary HCC patients compared with NAR, especially in those with MVI and tumor size ≤5 cm.

Conditional loss of geranylgeranyl diphosphate synthase alleviates acute obstructive cholestatic liver injury by regulating hepatic bile acid metabolism.

Previous studies have suggested that metabolites in the mevalonate pathway are involved in hepatic bile acid metabolism, yet the details of this relationship remain unknown. In this study, we found that the hepatic farnesyl pyrophosphate (FPP) level and the ratio of FPP to geranylgeranyl pyrophosphate (GGPP) were increased in mice with acute obstructive cholestasis compared with mice that underwent a sham operation. In addition, the livers of the mice with acute obstructive cholestasis showed lower expression of geranylgeranyl diphosphate synthase (GGPPS), which synthesizes GGPP from FPP. When Ggps1 was conditionally deleted in the liver, amelioration of liver injury, as shown by downregulation of the hepatic inflammatory response and decreased hepatocellular apoptosis, was found after ligation of the common bile duct and cholecystectomy (BDLC). Subsequently, liquid chromatography/mass spectrometry analysis showed that knocking out Ggps1 decreased the levels of hepatic bile acids, including hydrophobic bile acids. Mechanistically, the disruption of Ggps1 increased the levels of hepatic FPP and its metabolite farnesol, thereby resulting in farnesoid X receptor (FXR) activation, which modulated hepatic bile acid metabolism and reduced hepatic bile acids. It was consistently indicated that digeranyl bisphosphonate, a specific inhibitor of GGPPS, and GW4064, an agonist of FXR, could also alleviate acute obstructive cholestatic liver injury in vivo. In general, GGPPS is critical for modulating acute obstructive cholestatic liver injury, and the inhibition of GGPPS ameliorates acute obstructive cholestatic liver injury by decreasing hepatic bile acids, which is possibly achieved through the activation of FXR-induced bile acid metabolism.

Reduced triglyceride accumulation due to overactivation of farnesoid X receptor signaling contributes to impaired liver regeneration following 50% hepatectomy in extra­cholestatic liver tissue.

The aim of the present study was to investigate the role of triglyceride metabolism in the effect of obstructive cholestasis on liver regeneration following 50% partial hepatectomy (PH). Obstructive cholestatic rat models were achieved via ligation of the common bile duct (BDL). Following comparisons between hepatic pathological alterations with patients with perihilar cholangiocarcinoma, rats in the 7 day post­BDL group were selected as the BDL model for subsequent experiments. Liver weight restoration, proliferating cell nuclear antigen labeling index, cytokine and growth factor expression levels, and hepatic triglyceride content were evaluated to analyze liver regeneration post­PH within BDL and control group rats. The results of the present study revealed that obstructive cholestasis impaired liver mass restoration, which occurred via inhibition of early stage hepatocyte proliferation. In addition, reduced triglyceride content and inhibited expression of fatty acid ß­oxidation­associated genes, peroxisome proliferator activated receptor α and carnitine palmitoyltransferase, were associated with an insufficient energy supply within the BDL group post­PH. Notably, the expression levels of fatty acid synthesis­associated genes, including sterol­regulatory element­binding protein­1c, acetyl­coA carboxylase 1 and fatty acid synthase were also reduced within the BDL group, which accounted for the reduced triglyceride content and fatty acid utilization. Further investigation revealed that overactivated farnesoid X receptor (FXR) signaling may inhibit fatty acid synthesis within BDL group rats. Collectively, the role of triglycerides in liver regeneration following PH in extra­cholestatic livers was identified in the present study. Additionally, the results indicated that overactivated FXR signaling­induced triglyceride reduction is associated with insufficient energy supply and therefore contributes to the extent of impairment of liver regeneration following PH within extra­cholestatic livers.

Vertebral plate regeneration induced by radiation-sterilized allogeneic bone sheets in sheep.

OBJECTIVE: To evaluate the effects and mechanism of radiation-sterilized allogeneic bone sheets in inducing vertebral plate regeneration after laminectomy in sheep. METHODS: Twelve adult male sheep (aged 1.5 years and weighing 27 kg on average) provided by China Institute for Radiation Protection underwent L3-4 and L4-5 laminectomy. Then they were randomly divided into two groups: Group A (n=6) and Group B (n=6). The operated sites of L4-5 in Group A and L3-4 in Group B were covered by "H-shaped" freeze-drying and radiation-sterilized allogeneic bone sheets (the experimental segments), while the operated sites of L3-4 in Group A and L4-5 in Group B were uncovered as the self controls (the control segments). The regeneration process of the vertebral plate and the adhesion degree of the dura were observed at 4, 8, 12, 16, 20 and 24 weeks after operation. X-ray and CT scan were performed in both segments of L3-4 and L4-5 at 4 and 24 weeks after operation. RESULTS: In the experimental segments, the bone sheets were located in the anatomical site of vertebral plate, and no lumbar spinal stenosis or compression of the dura was observed. The bone sheets were absorbed gradually and fused well with the regenerated vertebral plate. While in the control segments, the regeneration of vertebral plate was not completed yet, the scar was inserted into the spinal canal, compressing the dura and the spinal cord, and the epidural area almost disappeared. Compared with the control segments, the dura adhesion degree in the experimental regenerated segments was much milder (P less than 0.01), the internal volume of the vertebral canal had no obvious change and the shape of the dura sack remained well without obvious compression. CONCLUSIONS: Freeze-drying and radiation-sterilized allogeneic bone sheets are ideal materials for extradural laminoplasty due to their good biocompatibility, biomechanical characteristics and osteogenic ability. They can effectively reduce formation of post-laminectomy scars, prevent recurrence of post-laminectomy spinal stenosis, and induce regeneration of vertebral plates.