Radical lymph node dissection and assessment:Impact on gallbladder cancer prognosis

AIM: To investigate the lymph node metastasis patterns of gallbladder cancer(GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor.METHODS: From May 1995 to December 2010,a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People's Hospital.A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder.Demographic,operative and pathologic data were recorded.The lymph nodes retrieved were examined histologically for metastases routinely from each node.The positive lymph node count(PLNC) as well as the total lymph node count(TLNC) was recorded for each patient.Then the metastatic to examined lymph nodes ratio(LNR) was calculated.Disease-specific survival(DSS) and predictors of outcome were analyzed.RESULTS: With a median follow-up time of 26.50 mo(range,2-132 mo),median DSS was 29.00 ± 3.92 mo(5-year survival rate,20.51%).Nodal disease was found in 37 patients(47.44%).DSS of node-negative patients was significantly better than that of nodepositive patients(median DSS,40 mo vs 17 mo,χ2= 14.814,P < 0.001),while there was no significant difference between N1 patients and N2 patients(median DSS,18 mo vs 13 mo,χ2= 0.741,P = 0.389).Optimal TLNC was determined to be four.When node-negative patients were divided according to TLNC,there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup(median DSS,37 mo vs 54 mo,χ2 = 0.715,P = 0.398).For node-positive patients,DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup(median DSS,13 mo vs 21 mo,χ2= 11.035,P < 0.001).Moreover,for node-positive patients,a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups(< 6 or ≥ 6,respectively;median DSS,15 mo vs 33 mo,χ2= 11.820,P < 0.001).DSS progressively worsened with increasing PLNC and LNR,but no definite cut-off value could be identified.Multivariate analysis revealed histological grade,tumor node metastasis staging,TNLC and LNR to be independent predictors of DSS.Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis.CONCLUSION: Both TLNC and LNR are strong predictors of outcome after curative resection for GBC.The retrieval and examination of at least 6 nodes can influence staging quality and DSS,especially in nodepositive patients.

Apoptosis inhibitory effect of anti-miR-146b on hippocampal neurons of OGD/R-induced injury

Objective:To construct a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in hippocampal neuronsin vitro, and to explore the inhibitory effect of anti-miR-146b on the apoptosis of hippocampal neurons of ischemic/reperfusion injury. Methods: Primary rat hippocampal neurons were cultured, and oxygen-glucose deprivation and reoxygenation (OGD/R) were constructed. The anti-miR-146b lentivirus was used to transfect the hippocampal neurons, and the cells were divided into the normal group, the OGD/R group and the OGD/R + anti-miR-146b group. Real time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of miR-146b, KLF7, Caspase-3, Bcl-2 and Bax in each group. Cell viability was detected by CCK8 assay, and apoptosis was detected by Hoechst33342/PI double staining.Results: Compared with the normal group, the cell morphology of the OGD/R group and the OGD/R + anti-miR-146b group was damaged, the cell activity was decreased, and the cell apoptosis rate was increased significantly (P<0.05). However, Compared with OGD/R group, the cell morphology of the OGD/R + KLF7 group was improved, the cell activity was increased, and the apoptosis rate was decreased significantly (P<0.05). Compared with the normal group, the mRNA expression levels of miR-146b, KLF7, Caspase-3, Bax and Bcl-2 in the OGD/R group and the OGD/R + KLF7 group was increased (P<0.05). Compared with the OGD/R group, the mRNA expression of KLF7, Bcl-2 were increased in the OGD/R + KLF7 group significantly, however, the mRNA expression of miR-146b, Caspase-3, Bax were decreased significantly (P<0.05).Conclusion:Anti-miR-146b play protective effect on hippocampal neurons of OGD/R-induced injury. The mechanism may be related to upregulation of KLF7 signaling pathway, downregulation expression of Caspase-3 and Bax, upregulation expression of Bcl-2, and inhibition of apoptosis induced by OGD/R.