γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase-to-platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases. AIM: To assess the prognostic value of GPR and to design a prognostic nomogram for GBC. METHODS: The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan-Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index. RESULTS: Patients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor-node-metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging. CONCLUSION: GPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC.

The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma.

Accumulating evidence has emerged revealing that noncoding RNAs (ncRNAs) play essential roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the complicated regulatory interactions among various ncRNAs in the development of HCC are not entirely understood. The newly discovered mechanism of competing endogenous RNAs (ceRNAs) uncovered regulatory interactions among different varieties of RNAs. In recent years, a growing number of studies have suggested that ncRNAs, including long ncRNAs, circular RNAs and pseudogenes, play major roles in the biological functions of the ceRNA network in HCC. These ncRNAs can share microRNA response elements to affect microRNA affinity with target RNAs, thus regulating gene expression at the transcriptional level and both physiological and pathological processes. The ncRNAs that function as ceRNAs are involved in diverse biological processes in HCC cells, such as tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis and chemoresistance. Based on these findings, ncRNAs that act as ceRNAs may be promising candidates for clinical diagnosis and treatments. In this review, we discuss the mechanisms and research methods of ceRNA networks. We also reviewed the recent advances in studying the roles of ncRNAs as ceRNAs in HCC and highlight possible directions and possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets. Finally, the limitations, gaps in knowledge and opportunities for future research are also discussed.

Fruits and vegetables consumption and the risk of gallstone diasease: A systematic review and meta-analysis.

BACKGROUND: The role of fruit and vegetables (FVs) consumption in decreasing gallstone disease risk remains contradictory. We performed a meta-analysis to analyze this potential correlation, followed by investigation of dose-response relationship of FVs consumption with gallstone disease. MATERIALS AND METHODS: PubMed, Embase, as well as Web of Science were searched to determine all published researches about the connection of FVs consumption with gallstone disease before March 2018. Relative risks (RRs) or odds ratios (ORs) along with corresponding 95% confidence intervals (CIs) was pooled utilizing random effect models, aiming at examining the correlation of FVs consumption with gallstone disease risk. RESULTS: One cross-sectional study, our case-control studies as well as nine cohort studies were enrolled, covering approximately 33,983 patients with gallstone disease and 1,53,3752 participants. In a pooled analysis, vegetables consumption was significantly related to a decreased gallstone disease risk, (RR = 0.83, 95% CI, 0.74-0.94, I = 91.1%), and for fruits consumption, RR was similar (RR = 0.88, 95%CI, 0.83-0.92, I = 0.01%). This inverse correlation of FVs consumption with gallstone disease risk was solid in most subgroup analysis. The nonlinear dose-response correlation indicated that gallstone risk was reduced by 4% (RR = 0.96, 95%CI, 0.93-0.98) and 3% (RR = 0.97, 95%CI, 0.96-0.98) for every 200 g per day increment in vegetables consumption (P = .001) and fruits consumption (P = .001), respectively. CONCLUSION: This study suggests vegetables and fruits consumption is correlated with a significantly reduced risk of gallstone disease.

Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery.

AIM: To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in cholangiocarcinoma (CCA) subjects receiving surgery. METHODS: In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics (including AAPR) were analyzed to determine predictors of post-operative overall survival and recurrence-free survival (RFS). In addition, univariate and multivariate Cox proportional hazards models were conducted, followed by application of time-dependent receiver operating curves to identify the optimal cut-off. RESULTS: Univariate and multivariate analyses revealed both decreased overall survival [hazard ratio (HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival (HR: 2.31, 95%CI: 1.40-3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥ 0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253 (83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low (< 0.41) AAPR group, which were significantly lower than those in the high (≥ 0.41) AAPR group (81.7%, 53.9%, and 33.4%, respectively) (P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis. CONCLUSION: Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.

Nomogram to predict overall survival after gallbladder cancer resection in China.

AIM: To integrate clinically significant variables related to prognosis after curative resection for gallbladder carcinoma (GBC) into a predictive nomogram. METHODS: One hundred and forty-two GBC patients who underwent curative intent surgical resection at Peking Union Medical College Hospital (PUMCH) were included. This retrospective case study was conducted at PUMCH of the Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC) in China from January 1, 2003 to January 1, 2018. The continuous variable carbohydrate antigen 19-9 (CA19-9) was converted into a categorical variable (cCA19-9) based on the normal reference range. Stages 0 to IIIA were merged into one category, while the remaining stages were grouped into another category. Pathological grade X (GX) was treated as a missing value. A multivariate Cox proportional hazards model was used to select variables to construct a nomogram. Discrimination and calibration of the nomogram were performed via the concordance index (C-index) and calibration plots. The performance of the nomogram was estimated using the calibration curve. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the predictive accuracy and net benefit of the nomogram, respectively. RESULTS: Of these 142 GBC patients, 55 (38.7%) were male, and the median and mean age were 64 and 63.9 years, respectively. Forty-eight (33.8%) patients in this cohort were censored in the survival analysis. The median survival time was 20 months. A series of methods, including the likelihood ratio test and Akaike information criterion (AIC) as well as stepwise, forward, and backward analyses, were used to select the model, and all yielded identical results. Jaundice [hazard ratio (HR) = 2.9; 95% confidence interval (CI): 1.60-5.27], cCA19-9 (HR = 3.2; 95%CI: 1.91-5.39), stage (HR = 1.89; 95%CI: 1.16-3.09), and resection (R) (HR = 2.82; 95%CI: 1.54-5.16) were selected as significant predictors and combined into a survival time predictive nomogram (C-index = 0.803; 95%CI: 0.766-0.839). High prediction accuracy (adjusted C-index = 0.797) was further verified via bootstrap validation. The calibration plot demonstrated good performance of the nomogram. ROC curve analysis revealed a high sensitivity and specificity. A high net benefit was proven by DCA. CONCLUSION: A nomogram has been constructed to predict the overall survival of GBC patients who underwent radical surgery from a clinical database of GBC at PUMCH.

Prognostic significance of the fibrinogen-to-albumin ratio in gallbladder cancer patients.

AIM: To investigate the prognostic role of fibrinogen-to-albumin ratio (FAR) on patients with gallbladder cancer (GBC) in this study. METHODS: One hundred and fifty-four GBC patients were retrospectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve (ROC curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses. RESULTS: ROC curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age (P = 0.045), jaundice (P < 0.001), differentiation (P = 0.002), resection margin status (P < 0.001), T stage (P < 0.001), TNM stage (P < 0.001), and CA199 (P < 0.001) as well as albumin levels (P < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio (HR): 2.343, 95% confidence interval (CI): 1.532-3.581, P < 0.001], TNM stage (P = 0.035), albumin level (HR = 0.595, 95%CI: 0.385-0.921, P = 0.020) and FAR (HR: 2.813, 95%CI: 1.765-4.484, P < 0.001) were independent prognostic factors in GBC patients. CONCLUSION: An elevated preoperative FAR was significantly correlated with unfavorable overall survival in GBC patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with GBC. The preoperative FAR could be used to predict the prognosis of GBC patients, which was easily accessible, cost-effective and noninvasive.

Prognostic impact of the red cell distribution width in esophageal cancer patients: A systematic review and meta-analysis.

AIM: To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width (RDW) in esophageal cancer (EC). METHODS: We searched the PubMed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible: (1) Studies including EC patients who underwent radical esophagectomy; (2) studies including patients with localized disease without distant metastasis; (3) studies including patients without preoperative neoadjuvant therapy; (4) studies including patients without previous antiinflammatory therapies and with available preoperative laboratory outcomes; (5) studies reporting association between the preoperative RDW and overall survival (OS)/disease-free survival (DFS)/cancer-specific survival (CSS); and (6) studies published in English. RESULTS: A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 0.97-1.57, P = 0.000] or DFS (HR = 1.42, 95%CI: 0.96-1.88, P = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13% (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000), when the patient number ≤ 400 (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) and when the study type was retrospective (HR = 1.42, 95%CI : 1.16-1.69, P = 0.000). CONCLUSION: Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value.

Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients.

AIM: To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma (GBC). METHODS: The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. Based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0. RESULTS: ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival (OS) (HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735 (for preoperative plasma fibrinogen only) and 0.729 (for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199 (P < 0.001), resection margin (P < 0.001) and TNM stage (P = 0.010) were independent prognostic factors for GBC. CONCLUSION: The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.

Angular-Shaped Naphthalene Bis(1,5-diamide-2,6-diylidene)malononitrile for High-Performance, Air-Stable N-Type Organic Field-Effect Transistors.

The synthesis, characterization, and application of two angular-shaped naphthalene bis(1,5-diamide-2,6-diylidene)malononitriles (NBAMs) as high-performance air-stable n-type organic field effect transistor (OFET) materials are reported. NBAM derivatives exhibit deep lowest-unoccupied molecular orbital (LUMO) levels, suitable for air-stable n-type OFETs. The OFET device based on NBAM-EH fabricated by vapor deposition exhibits a maximum electron mobility of 0.63 cm2 V-1 s-1 in air with an on/off current ratio ( Ion/ Ioff) of 105.

Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer.

AIM: To detect the expression of threonine and tyrosine kinase (TTK) in gallbladder cancer (GBC) specimens and analyze the associations between TTK expression and clinicopathological parameters and clinical prognosis. METHODS: A total of 68 patients with GBC who underwent surgical resection were enrolled in this study. The expression of TTK in GBC tissues was detected by immunohistochemistry. The assessment of TTK expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of TTK in the cytoplasm and nucleus was scored separately to achieve respective H-score values. The correlations between TTK expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. RESULTS: In both the nucleus and cytoplasm, the expression of TTK in tumor tissues was significantly lower than that in normal tissues (P < 0.001 and P = 0.026, respectively). Using the median H-score as the cutoff value, it was discovered that, GBC patients with higher levels of TTK expression in the nucleus, but not the cytoplasm, had favorable overall survival (P < 0.001), and it was still statistically meaningful in Cox regression analysis. Further investigation indicated that there were close negative correlations between TTK expression and tumor differentiation (P = 0.041), CA 19-9 levels (P = 0.016), T stage (P < 0.001), nodal involvement (P < 0.001), distant metastasis (P = 0.024) and TNM stage (P < 0.001). CONCLUSION: The expression of TTK in GBC is lower than that in normal tissues. Higher levels of TTK expression in GBC are concomitant with longer overall survival. TTK is a favorable prognostic biomarker for patients with GBC.