Risk factors for long-term prognosis of hepatocellular carcinoma patients after anatomic hepatectomy.

BACKGROUND: The risk factors for patients with major postoperative complications immediately after liver resection have been identified; however, the intermediate and long-term prognoses for these patients have yet to be determined. AIM: To evaluate the factors responsible for the long-term recurrence-free survival rate in patients with hepatocellular carcinoma (HCC) following anatomic hepatectomy. METHODS: We performed a retrospective analysis of 74 patients with HCC who underwent precise anatomic hepatectomy at our institution from January 2013 to December 2015. The observational endpoints for this study were the tumor recurrence or death of the HCC patients. The overall follow-up duration was three years. The recurrence-free survival curves were plotted by the Kaplan-Meier method and were analyzed by the log-rank test. The value of each variable for predicting prognosis was assessed via multivariate Cox proportional hazards regression analysis. RESULTS: The 1-year and 3-year recurrence-free survival rates of HCC patients were 68.92% and 55.41%, respectively, following anatomic liver resection. The results showed that the 3-year recurrence-free survival rate in HCC patients was closely related to preoperative cirrhosis, jaundice level, tumor stage, maximal tumor diameter, complications of diabetes mellitus, frequency of intraoperative hypotensive episodes, estimated blood loss (EBL), blood transfusion, fluid infusion, and postoperative infection (P < 0.1). Based on multivariate analysis, preoperative cirrhosis, tumor stage, intraoperative hypotension, and EBL were identified to be predictors of 3-year recurrence-free survival in HCC patients undergoing anatomic hepatectomy (P < 0.05). CONCLUSION: Tumor stage and preoperative cirrhosis adversely affect the recurrence-free survival rate in HCC patients following anatomic hepatectomy. The long-term recurrence-free survival rate of patients with HCC is closely related to intraoperative hypotension and EBL.

Inhibition of glycogen synthase kinase-3ß is involved in cardioprotection by α7nAChR agonist and limb remote ischemic postconditionings.

The present study was designed to determine whether glycogen synthase kinase-3ß (GSK-3ß) was involved in the cardioprotection by α7 nicotinic acetylcholine receptor (α7nAChR) agonist and limb remote ischemic postconditionings. Forty male Sprague-Dawley rats were randomly divided equally into control (C), α7nAChR agonist postconditioning (P), limb remote ischemic postconditioning (L), combined α7nAChR agonist and limb remote ischemic postconditioning (P+L) groups. At the end of experiment, serum cTnI, creatine kinase-MB (CK-MB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high mobility group protein (HMGB1) and interleukin-10 (IL-10) levels were measured; infarct size (IS), myocardial expressions of GSK-3ß, p-GSK-3ß (Ser9), nuclear factor-κB (NF-κB) and p-NF-κB (Ser536) in the ischemic area were assessed. The results showed that compared with group C, IS, serum cTnI and CK-MB levels obviously decreased in groups P, L and P+L. Compared with groups P and L, IS, serum cTnI and CK-MB levels significantly decreased in group P+L. Compared with group C, serum TNF-α, IL-6 and HMGB1 levels, and myocardial expression of p-NF-κBp65 (Ser536) evidently decreased, and myocardial expression of p-GSK-3ß (Ser9) obviously increased in groups P, L and P+L. Compared with group P, serum TNF-α, IL-6 and HMGB1 levels and myocardial expression of p-NF-κBp65 (Ser536) significantly increased, and myocardial expression of p-GSK-3ß (Ser9) evidently decreased in group L. Compared with group L, serum TNF-α, IL-6, HMGB1 levels, and myocardial expression of p-NF-κBp65 (Ser536) significantly decreased, and myocardial expression of p-GSK-3ß (Ser9) obviously increased in group P+L. In conclusion, our findings indicate that inhibition of GSK-3ß to decrease NF-κB transcription is one of cardioprotective mechanisms of α7nAChR agonist and limb remote ischemic postconditionings by anti-inflammation, but improved cardioprotection by combined two interventions is not completely attributable to an enhanced anti-inflammatory mechanism.

Combined Vagal Stimulation and Limb Remote Ischemic Perconditioning Enhances Cardioprotection via an Anti-inflammatory Pathway.

Various combined interventions to acquire enhanced cardioprotection are prevalent focuses of current research. This randomized experiment assessed whether combined vagal stimulation perconditioning (VSPerC) and limb remote ischemic perconditioning (LRIPerC) improved cardioprotection compared to the use of either treatment alone in an in vivo rat model of myocardial ischemia/reperfusion injury. A total of 100 male Sprague Dawley rats were randomly allocated into five groups: sham group, ischemia/reperfusion (IR) group, VSPerC group, LRIPerC group, and combined VSPerC and LRIPerC (COMPerC) group. Serum enzymatic markers, inflammatory cytokines, myocardial inflammatory cytokines, and infarct size were assessed. Infarct size decreased significantly in the COMPerC group compared to the VSPerC and LRIPerC groups. Serum intercellular adhesion molecule 1 (ICAM-1) level at 120 min of reperfusion, myocardial interleukin-1 (IL-1), ICAM-1, and tumor necrosis factor α (TNF-α) levels in the ischemic region decreased significantly in the COMPerC group compared to the VSPerC group, but myocardial IL-10 levels in the nonischemic region increased markedly in the COMPerC group. Serum TNF-α levels at 30, 60, and 120 min of reperfusion; serum IL-1, IL-6, ICAM-1, and high mobility group box-1 protein (HMGB-1) levels at 120 min of reperfusion; and myocardial IL-1, IL-6, ICAM-1, and TNF-α levels in the ischemic region decreased significantly in the COMPerC group compared to the LRIPerC group. However, myocardial IL-10 levels in both ischemic and nonischemic regions were evidently higher in the COMPerC group. This study concludes that combined VSPerC and LRIPerC enhances cardioprotection compared to either treatment alone. This result is likely attributable to a more potent regulation of inflammation.

Optimal intervention time of vagal stimulation attenuating myocardial ischemia/reperfusion injury in rats.

OBJECTIVE: To determine the optimal intervention time of the vagal stimulation (VS) attenuating myocardial ischemia/reperfusion injury (IRI). METHODS: One hundred and twenty male SD rats were randomly allocated into six groups: sham group, IRI group, the VS performed at 15 min of ischemia (VSI15) group, the VS performed immediately before reperfusion (VSR0) group, the VS performed at 30 min of reperfusion (VSR30) group, and the VS performed at 60 min of reperfusion (VSR60) group. Rats in each group were further allocated into subgroups A and B. In each group, the hemodynamics and ventricular arrhythmias were continuously observed. In the subgroup A, serum inflammatory cytokine levels were tested, and infarct size was assessed. In the subgroup B, myocardial inflammatory cytokine levels in both ischemic and non-ischemic regions were assayed. RESULTS: As compared to the IRI, VSR0, VSR30 and VSR60 groups, infarct size, serum HMGB-1 and ICAM-1 levels at 120 min of reperfusion, myocardial HMGB-1, IL-1 and IL-6 levels in non-ischemic region, myocardial ICAM-1 level in ischemic region were all significantly decreased in the VSI15 group. Compared with the IRI group, myocardial IL-10 levels in both ischemic and non-ischemic regions were significantly increased in the VSI15 group. Compared to the IRI, VSR0, VSR30 and VSR60 groups, incidence and score of ventricular arrhythmia during initial reperfusion were significantly decreased in the VSI15 group. CONCLUSIONS: The VS performed at 15 min of ischemia provides the best protection against myocardial IRI. Also, early modulation on inflammatory responses caused by myocardial IRI may contribute to this best cardioprotection.