These data suggest that (1) the proliferative activity of a resected specimen predicted the prognosis in patients with HCC; (2) the proliferative activity was closely correlated with the glucose metabolism, but not with angiogenesis.
Preoperative FDG-PET predicts hepatocellular carcinoma recurrences within the MC or no recurrence and recurrences after 1 year or later. FDG-PET may be useful for selecting appropriate patients for liver resection as an initial surgical strategy.
BackgroundAlthough animal studies models are frequently used for the purpose of attenuating ischemia reperfusion injury (IRI) in liver transplantation (LT), many of pharmacological agents have not become part of clinical routine.MethodsA search was performed using the PubMed database to identify
agents, from which 58 articles containing 2700 rat LT procedures were selected. The identified pharmacological agents were categorized as follows: I - adenosine agonists, nitric oxide agonists, endothelin antagonists, and prostaglandins, II – Kupffer cell inactivator, III - complement inhibiter, IV - antioxidant, V - neutrophil inactivator, VI -anti-apoptosis agent, VII - heat shock protein and nuclear factor kappa B inducer, VIII - metabolic agent, IX - traditional Chinese medicine, and X - others. Meta-analysis using 7-day-survival rate was also performed with Mantel-Haenszel's Random effects model.ResultsThe categorization revealed that the rate of donor-treated experiments in each group was highest for agents from Group II (70%) and VII (71%), whereas it was higher for agents from Group V (83%) in the recipient-treated experiments. Furthermore, 90% of the experiments with agents in Group II provided 7-day-survival benefits. The Risk Ratio (RR) of the meta-analysis was 2.43 [95% CI: 1.88-3.14] with moderate heterogeneity. However, the RR of each of the studies was too model-dependent to be used in the search for the most promising pharmacological agent.ConclusionWith regard to hepatic IRI pathology, the categorization of agents of interest would be a first step in designing suitable multifactorial and pleiotropic approaches to develop pharmacological strategies.
After extended hepatectomy, excessive shear stress in the remnant liver causes postoperative liver failure. Olprinone (OLP), a selective phosphodiesterase I inhibitor, has been reported to improve microcirculation and attenuate inflammation. The aim of this study was to investigate the effects of OLP on shear stress in rats with an excessive hepatectomy (EHx) model. In this study, EHx comprised 90% hepatectomy with ligation of the left and right Glisson's sheaths in Lewis rats. OLP or saline was intraperitoneally administered with an osmotic pump 48 hours before EHx. To evaluate the shear stress, we measured the portal vein (PV) pressure. We also assessed sinusoidal endothelial cell injury by immunohistochemistry and electron microscopy. Furthermore, we assessed apoptosis in the liver with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method. Treatment with OLP up-regulated hepatic endothelial nitric oxide synthase (eNOS) expression. The increase in the PV pressure due to Glisson's sheath ligation was attenuated in OLPtreated rats during a 30-minute period after ligation. Treatment with OLP preserved sinusoidal endothelial cells and reduced apoptosis in the remnant liver. The probability of survival in the OLP-treated rats was significantly better than that in the controls (33.3% versus 13.3%). Furthermore, the postoperative eNOS activity in the OLP-treated rats was higher than that in the controls. The administration of Nx-nitro-l-arginine methyl ester to OLP-treated rats eliminated the effects of OLP on PV pressure and survival after EHx. Therefore, we concluded that OLP attenuates excessive shear stress through the upregulation of eNOS and improves the survival rate after EHx.
Everolimus is an orally administrated mammalian target of rapamycin (mTOR) inhibitor. Several large-scale randomized controlled trials (RCTs) have demonstrated the survival benefits of everolimus at the dose of 10 mg/day for solid cancers. Furthermore, mTOR-inhibitor-based immunosuppression is associated with survival benefits for patients with hepatocellular carcinoma (HCC) who have received liver transplantation. However, a low rate of tumor reduction and some adverse events have been pointed out. This review summarizes the antitumor effects and adverse events of everolimus and evaluates its possible application in advanced HCC. For the meta-analysis of adverse events, we used the RCTs for solid cancers. The odds ratios of adverse events were calculated using the Peto method. Manypreclinical studies demonstrated that everolimus had antitumor effects such as antiproliferation and antiangiogenesis. However, some differences in the effects were observed among in vivo animal studies for HCC treatment. Meanwhile, clinical studies demonstrated that the response rate of single-agent everolimus was low, though survival benefits could be expected. The meta-analysis revealed the odds ratios (95% confidence interval [CI]) of stomatitis: 5.42 [4.31–6.73], hyperglycemia: 3.22 [2.37–4.39], anemia: 3.34 [2.37–4.67], pneumonitis: 6.02 [3.95–9.16], aspartate aminotransferase levels: 2.22 [1.37–3.62], and serum alanine aminotransferase levels: 2.94 [1.72–5.02], respectively. Everolimus at the dose of 10 mg/day significantly increased the risk of the adverse events. In order to enable its application to the standard conventional therapies of HCC, further studies are required to enhance the antitumor effects and manage the adverse events of everolimus.
Backgrounds: Prognosis for patients with advanced intrahepatic cholangiocarcinoma (ICC) with intrahepatic metastasis (IM), vascular invasion (VI), or regional lymph node metastasis (LM) remains poor. The aim of this study was to clarify the indications for surgical resection for advanced ICC. Methods: We retrospectively divided 213 ICC patients treated at Kyoto University Hospital between 1993 and 2013 into a resection (n=164) group and a non-resection (n=49) group. Overall survival was assessed after stratification for the presence of IM, VI, or LM. Results: Overall median survival times (MSTs) for the resection and non-resection groups were 26.0 and 7.1 months, respectively (p<0.001). After stratification, MSTs in the resection and non-resection groups, respectively, were 18.7 vs. 7.0 months for patients with IM (p<0.001), 23.4 vs. 5.7 months for those with VI (p<0.001), and 12.8 vs. 5.5 months for those with LM (p<0.001). Conclusion: When macroscopic curative resection is possible, surgical resection can be justified for some advanced ICC patients with IM, VI, or LM.
The present study demonstrated that Th2-dominant splenic lymphocytes migrate into the liver and promote liver fibrosis by shifting the cytokine balance towards Th2 dominance. Splenectomy suppresses the progression of fibrosis at least partly by restoring the Th1/Th2 balance.
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