Lymphocyte-to-monocyte ratio predicts survival of patients with hepatocellular carcinoma after curative resection

AIM: To investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio(LMR) in patients with hepatocellular carcinoma(HCC) undergoing curative hepatectomy.METHODS: Clinicopathological data of 210 hepatitis B virus(HBV)-associated HCC patients who were treated by radical hepatic resection between 2003 and 2010 were retrospectively analyzed. None of the patients received any preoperative anticancer therapyor intraoperative radiofrequency ablation. The diagnosis was confirmed by pathological examination after surgery. Absolute peripheral blood lymphocyte and monocyte counts were derived from serum complete blood cell count before surgery,and LMR was calculated by dividing lymphocyte count by monocyte count. The best cutoff was determined by receiver operating characteristics(ROC) curve analysis. Correlations between LMR levels and clinicopathological features were assessed using the χ2 test. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of LMR and other clinicopathological factors on overall survival(OS) and recurrence-free survival(RFS),using the Cox proportional hazards model.RESULTS: The optimal cutoff value of LMR for survival analysis was 3.23,which resulted in the most appropriate sensitivity of 55.3% and specificity of 74.7%,with the area under the curve(AUC) of 0.66(95%CI: 0.593-0.725). All patients were dichotomized into either a low(≤ 3.23) LMR group(n = 66) or a high(> 3.23) LMR group(n = 144). A low preoperative LMR level was significantly correlated with the presence of cirrhosis,elevated levels of total bilirubin and larger tumor size. Patients with a low LMR level had significantly reduced 5-year OS(61.9% vs 83.2%,P < 0.001) and RFS(27.8% vs 47.6%,P = 0.009) compared to those with a high LMR level. Multivariate analyses indicated that a lower LMR level was a significantly independent predictor of inferior OS(P = 0.003) and RFS(P = 0.006). Subgroup analysis indicated that survival outcome was significantly more favorable in cirrhotic patients with LMR > 3.23. However,there were no differences between low and high LMR groups for OS and RFS in non-cirrhotic patients.CONCLUSION: Preoperative LMR was demonstrated for the first time to serve as an independent prognostic factor in HBV-associated HCC patients after curative resection. Prospective studies with larger cohorts for validation are warranted.

Poor oncologic outcomes of hepatocellular carcinoma patients with intra-abdominal infection after hepatectomy

AIM: To evaluate the impact of postoperative infectious complications on hepatocellular carcinoma following curative hepatectomy.METHODS:We performed a retrospective analysis of200 hepatocellular carcinoma patients who underwent hepatectomy at our institution between September2003 and June 2011.The patients’demographics,clinicopathological characteristics and postoperative infectious complications were analyzed.The ClavienDindo classification was adopted to assess the severity of complications.The dynamic change in the neutrophilto-lymphocyte ratio,defined as the absolute neutrophil count divided by the absolute lymphocyte count,after surgery was also investigated.The observation endpoints for this study were recurrence-free survival and overall survival of the patients.Statistical analysis of the survival curves was performed using the KaplanMeier method and the log-rank test.The prognosticvalue of each variable for predicting prognosis was assessed via multivariate Cox proportional hazards regression analysis.The cutoff score for each variable was selected based on receiver operating characteristic curve analysis.All statistical tests were two-sided,and significance was set at P<0.05.RESULTS:The median age of the patients was 49years,and the majority of patients were male(86%)and had been infected with hepatitis B virus(86%).The 30-d postoperative infectious complication rate was34.0%(n=68).Kaplan-Meier survival analysis revealed that postoperative infection was significantly correlated with tumor recurrence(P<0.001).The postoperative intra-abdominal infection group exhibited a worse prognosis than the non-intra-abdominal infection group(P<0.001).A significantly increased incidence of postoperative intra-abdominal infection was observed in the patients with hepatic cirrhosis(P=0.028),concomitant splenectomy(P=0.007)or vascular invasion(P=0.026).The patients who had an elevated postoperative neutrophil-to-lymphocyte ratio change(>1.643)clearly exhibited poorer recurrence-free survival than those who did not(P=0.009),although no significant correlation was observed between overall survival and the change in the postoperative neutrophilto-lymphocyte ratio.Based on multivariate analysis,hepatitis B surface antigen positivity,Child-TurcottePugh class B,an elevated postoperative neutrophilto-lymphocyte ratio change and intra-abdominal infection were significant predictors of poor recurrencefree survival.Hepatic cirrhosis,the maximal tumor diameter and intra-abdominal infection were significant predictors of overall survival.CONCLUSION:Postoperative intra-abdominal infection adversely affected oncologic outcomes,and the change in postoperative neutrophil-to-lymphocyte ratio was a good indicator of tumor recurrence in hepatocellular carcinoma patients after curative hepatectomy.

Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer

BACKGROUND Pancreatic cancer is a major cause of cancer-related death,with a 5-year overall survival rate being below 5%.The main causes of poor prognosis in pancreatic cancer include easy metastasis,high recurrence rate,and robust drug resistance.Gemcitabine is a first-line drug for patients with unresectable pancreatic cancer.However,due to drug resistance,the clinical effect is not satisfactory.ADAM28 is reported as a tumor promoter in some cancers,but its role in pancreatic cancer and gemcitabine chemoresistance in pancreatic cancer has not been elucidated.AIM To identify if ADAM28 can act as an important target to reverse the gemcitabine drug resistance in pancreatic cancer.METHODS RNA-sequence analysis was applied to explore the potential targets involved in the gemcitabine of pancreatic cancer.SW1990 pancreatic cancer cells were treated with an increased dose of gemcitabine,and the mRNA levels of ADAM28 were evaluated by RT-PCR.The protein and mRNA levels of ADAM28 were confirmed in the gemcitabine resistant and parallel SW1990 cells.The ADAM28 expression was also assessed in TCGA and GEO databases,and the results were confirmed in the collected tumor and adjacent normal tissues.The overall survival(OS)rate and relapse-free survival(RFS)rate of pancreatic cancer patients with high ADAM28 level and low ADAM28 level in TCGA were evaluated with Kaplan-Meier Plotter.Furthermore,the OS rate was calculated in pancreatic cancer patients with high tumor mutation burden(TMB)and low TMB.CCK-8 assay was used to examine the effect of ADAM28 on the viability of SW1990 cells.The ADAM28 and its co-expressed genes were analyzed in the cBioPortal for cancer genomics and subjected to GSEA pathway analysis.The correlations of ADAM28 with GSTP1,ABCC1,GSTM4,and BCL2 were analyzed based on TCGA data on pancreatic cancer.RESULTS RNA-sequence analysis identified that ADAM28 was overexpressed in gemcitabine-resistant cells,and gemcitabine treatment could induce the expression of ADAM28.The mRNA and protein levels of ADAM28 were elevated in gemcitabine-resistant SW1990 cells compared with parallel cells.Also,the expression of ADAM28 was upregulated in pancreatic tumor tissues against normal pancreatic tissues.Notably,ADAM28 was highly expressed in the classical type than in the basal tumor type.Furthermore,the high expression of ADAM28 was associated with low OS and RFS rates.Interestingly,the high levels of ADAM28 was associated with a significantly lower OS rate in the high TMB patients,but not in the low TMB patients.Moreover,overexpression of ADAM28 could reduce the cell viability inhibition by gemcitabine,and knockdown of ADAM28 could enhance the proliferation inhibition by gemcitabine.The GSEA analysis showed that ADAM28 was related to the regulation of drug metabolism,and ADAM28 was significantly positively correlated with GSTP1,ABCC1,GSTM4,and BCL2.CONCLUSION This study demonstrates that ADAM28 is overexpressed in pancreatic cancer,and closely involved in the regulation of gemcitabine resistance.Overexpression of ADAM28 is a novel prognostic biomarker in pancreatic cancer.

Problem analysis and solutions of the B-ultrasound-guided peripherally inserted central catheter process

Objective： The purpose of this study was to address the issues that occur during the B-ultrasound guided peripherally inserted central catheter（PICC） process and to give a summary of the effective management to these issues accordingly.Methods： The information was collected retrospectively on all of the 1950 PICCs inserted during the 2-year period from July 2013 to July 2015. PICC catheter insertion was performed using the Seldinger approach and was delivered from the basilic vein to the superior vena cava in a B-ultrasound guided manner. Moreover, the point raised during the PICC process would be treated immediately.Results： All of the PICCs were inserted successfully. The problems encountered are shown in the inserted central catheter（PICC） process, such as failures of venipuncture, the problem of inserting guide wire, the catheter was dif？cult to be delivered etc.Conclusions： The B-ultrasound guided approach enhanced the average success regarding the PICC insertion, particularly for the subset with a poor condition in the elbow super？cial vein. Due to the items that emerged in the PICC process, the effective prevention prior to surgery and treatment during the operation would be necessary.

Past and future of the central double-degenerate core of Henize 2–428

It has been suggested that Type Ia supernovae(SNe Ia) could be produced in the conditions of the violent merger scenario of the double-degenerate model, in which a thermonuclear explosion could be produced when a double carbon-oxygen white dwarf(CO WD) merges. It has been recently found that the nucleus of the bipolar planetary nebula Henize 2–428 consists of a double CO WD system that has a total mass of^1.76 M⊙, a mass ratio of^1 and an orbital period of^4.2 h, which is the first and only discovered progenitor candidate for an SN Ia predicted by the violent merger scenario. In this work, we aim to reproduce the evolutionary history of the central double CO WD of Henize 2–428. We find that the planetary nebula Henize 2–428 may originate from a primordial binary that has a^5.4 M⊙primary and a^2.7 M⊙secondary with an initial orbital period of^15.9 d. The double CO WD was formed after the primordial binary experienced two Roche-lobe overflows and two common-envelope ejection processes.According to our calculations, it takes about^840 Myr for the double CO WD to merge and form an SN Ia driven by gravitational wave radiation after their birth. To produce the current status of Henize 2–428,a large common-envelope parameter is needed. We also estimate that the rate of SNe Ia from the violent merger scenario is at most 2.9 × 10^(-4) yr^(-1), and that the delay time is in the range of^90 Myr to the Hubble time.