Myong Kim

Prognostic Role of Survivin in Bladder Cancer: A Systematic Review and Meta-Analysis

Purpose The objective of the present study was to conduct a systematic review and meta-analysis of published literature investigating the survivin expression and its effects on bladder cancer prognosis. Materials and Methods We carefully searched online Pubmed, Cochrane Library and SCOPUS database from August 1997 to May 2013. Results A total of 14 articles met the eligibility criteria for this systematic review. The eligible studies included a total of 2,165 patients with a median number of 155 patients per study (range: 17–726). Of the 14 studies, nine evaluated immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. In non-muscle invasive bladder tumor, the pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.81; 95% confidence interval [CI], 1.30–2.52), progression-free survival (pooled HR, 2.12; 95% CI, 1.60–2.82), cancer-specific survival (pooled HR, 2.01; 95% CI, 1.32–3.06), and overall survival (pooled HR, 1.53; 95% CI, 1.02–2.29). The overall HRs by survivin status were robust across advanced stages. When only adjusted survival data were included, statistically significant differences were identified for all survival subgroup analyses. There was no between-study heterogeneity in the effect of survivin status on the majority of meta-analyses. There was no clear evidence of publication bias in this meta-analysis. Conclusions Survivin expression indicates worse prognosis in patients with bladder cancer but the results should be interpreted with caution. It is necessary that better-designed studies with standardized assays need to provide a better conclusion about the relationship between survivin expression and the outcome of patients with bladder cancer.

Presence of lymphovascular invasion in urothelial bladder cancer specimens after transurethral resections correlates with risk of upstaging and survival: A systematic review and meta-analysis

OBJECTIVES This study aimed to elucidate the relationship between lymphovascular invasion (LVI) at transurethral resection of bladder tumor (TURBT) and the risk of pathologic upstaging as well as the clinical outcomes. MATERIALS AND METHODS PubMed, Scopus, Web of Science, and Cochrane Library databases were searched from the respective dates of inception until November 11, 2013. RESULTS A total of 16 articles met the eligibility criteria for this systematic review, which included a total of 3,905 patients. LVI was detected in 18.6% of TURBT specimens. A significant association was found between LVI at TURBT and pathologic upstaging of bladder cancer (odds ratio = 2.21, 95% CI: 1.44-3.39) without heterogeneity (I(2) = 45%, P = 0.14). The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (HR = 1.47, 95% CI: 1.24-1.74), progression-free survival (HR = 2.28, 95% CI: 1.45-3.58), and disease-specific survival (HR = 1.35, 95% CI: 1.01-1.81), but not for overall survival (HR = 1.55, 95% CI: 0.90-2.67). Tests of inconsistency for disease-specific survival (I(2) = 66%, P = 0.007) and overall survival (I(2) = 72%, P = 0.03) could not exclude a significant heterogeneity. The results of the Begg and the Egger tests showed that there was evidence of publication bias on pathologic upstaging and progression-free survival. CONCLUSIONS The data obtained in this meta-analysis indicate that the presence of LVI at TURBT portends the increased risk of pathologic upstaging and may provide additional prognostic information. However, a large, well-designed, prospective study is needed to investigate potential treatment options for bladder cancer with LVI.

Prognostic Significance of Lymphovascular Invasion in Radical Cystectomy on Patients with Bladder Cancer: A Systematic Review and Meta-Analysis

Purpose The objective of the present study was to conduct a systematic review and meta-analysis of published literature to appraise the prognostic value of lymphovascular invasion (LVI) in radical cystectomy specimens. Materials and Methods Following the PRISMA statement, PubMed, Cochrane Library, and SCOPUS database were searched from the respective dates of inception until June 2013. Results A total of 21 articles met the eligibility criteria for this systematic review, which included a total of 12,527 patients ranging from 57 to 4,257 per study. LVI was detected in 34.6% in radical cystectomy specimens. LVI was associated with higher pathological T stage and tumor grade, as well as lymph node metastasis. The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.61; 95% confidence interval [CI], 1.26–2.06), cancer-specific survival (pooled HR, 1.67; 95% CI, 1.38–2.01), and overall survival (pooled HR, 1.67; 95% CI, 1.38–2.01), despite the heterogeneity among included studies. On sensitivity analysis, the pooled HRs and 95% CIs were not significantly altered when any one study was omitted. The funnel plot for overall survival demonstrated a certain degree of asymmetry, which showed slight publication bias. Conclusions This meta-analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy. Adequately designed prospective studies are required to provide the precise prognostic significance of LVI in bladder cancer.

Synthesis of 2-(3′-Azido- and 3′-Amino-3′-deoxy-β-D-ribofuranosyl)thiazole-4-carboxamide

Abstract In view of biological activities of tiazofurin and azido or aminosugar nucleosides, novel azido- and amino-substituted tiazofurin derivatives (1 and 2) were efficiently synthesized starting from 1,2;5,6-di-O-isopropylidene-D-glucose.

Preoperative serum albumin as a prognostic factor in patients with upper urinary tract urothelial carcinoma

PURPOSE The study evaluated whether preoperative measures of the C-reactive protein-systemic inflammatory response may predict cancer survival independent of tumor stage in patients with upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS Between September 1999 and October 2010, 181 patients submitted to radical nephroureterectomy were available for evaluation. Multivariate survival analyses were performed using Coxs proportional hazards model and the coefficient for each factor was divided by the highest coefficient, multiplied by 4, and rounded to the nearest integer. RESULTS Multivariate analyses showed that tumor location, pathologic T stage, lymphovascular invasion, margin status, and albumin level were independent contributors. The bootstrap-corrected C statistics of the model were 0.813 for disease-specific survival and 0.755 for overall survival, respectively. For time to disease-specific and overall mortality for patients, integrated area under the curve values were 0.792 and 0.739, respectively. When patients were clustered into three groups according to their model-predicted survival, the 5-year disease-specific survival in the low-, intermediate- and high-risk group was 95.4%, 76.2%, and 36.9%, respectively (p<0.001), and were 87.8%, 54.4%, and 31.8%, respectively, for overall survival (p<0.001). Decision curve analysis revealed that the use of model was associated with net benefit gains relative to the treat-all strategy. CONCLUSIONS Pretreatment albumin is a simple biomarker based on routinely available well-standardized measures, and is not an expensive and time-consuming process. Hypoalbuminemia is an independent marker of poor prognosis in patients with upper urinary tract urothelial carcinoma.

Risk Prediction Models of Locoregional Failure After Radical Cystectomy for Urothelial Carcinoma: External Validation in a Cohort of Korean Patients

PURPOSE To evaluate the predictive accuracy and general applicability of the locoregional failure model in a different cohort of patients treated with radical cystectomy. METHODS AND MATERIALS A total of 398 patients were included in the analysis. Death and isolated distant metastasis were considered competing events, and patients without any events were censored at the time of last follow-up. The model included the 3 variables pT classification, the number of lymph nodes identified, and margin status, as follows: low risk (≤pT2), intermediate risk (≥pT3 with ≥10 nodes removed and negative margins), and high risk (≥pT3 with <10 nodes removed or positive margins). RESULTS The bootstrap-corrected concordance index of the model 5 years after radical cystectomy was 66.2%. When the risk stratification was applied to the validation cohort, the 5-year locoregional failure estimates were 8.3%, 21.2%, and 46.3% for the low-risk, intermediate-risk, and high-risk groups, respectively. The risk of locoregional failure differed significantly between the low-risk and intermediate-risk groups (subhazard ratio [SHR], 2.63; 95% confidence interval [CI], 1.35-5.11; P<.001) and between the low-risk and high-risk groups (SHR, 4.28; 95% CI, 2.17-8.45; P<.001). Although decision curves were appropriately affected by the incidence of the competing risk, decisions about the value of the models are not likely to be affected because the model remains of value over a wide range of threshold probabilities. CONCLUSIONS The model is not completely accurate, but it demonstrates a modest level of discrimination, adequate calibration, and meaningful net benefit gain for prediction of locoregional failure after radical cystectomy.

Synthesis of 3'-deoxy-3'-C-hydroxymethyl analogues of tiazofurin and ribavirin.

On the basis of potent biological activity of 3′-branched-3′-deoxynucleoside analogues, novel ribavirin and tiazofurin derivatives with 3′-C-hydroxymethyl substituent were synthesized, starting from D-xylose.

Synthesis and Biological Evaluation of Novel Apio Nucleosides with Thiazole‐4‐carboxamide and 1,2,4‐Triazole‐3‐carboxamide

In view of biological activities of azole nucleosides and apio‐dideoxynucleoside, novel apio nucleoside analogues (1 and 2) with thiazole and triazole base moiety were synthesized using 2,3‐O‐isopropylidene‐apio‐β‐d‐furanose (3), which was prepared from d‐mannose.

Synthesis of homo-N-nucleoside with 1,2,4-triazole-3-carboxamide.

On the basis of potent biological activities of ribavirin and homo-N-nucleosides, a novel homo-N-1,2,4-triazole-3-carboxamide derivative 1 was synthesized starting from 2,3,5-tri-O-benzoyl-ribofuranosyl-1-acetate as a potential antiviral agent.

Non-invasive clinical parameters for the prediction of urodynamic bladder outlet obstruction: analysis using causal Bayesian networks.

Purpose To identify non-invasive clinical parameters to predict urodynamic bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH) using causal Bayesian networks (CBN). Subjects and Methods From October 2004 to August 2013, 1,381 eligible BPH patients with complete data were selected for analysis. The following clinical variables were considered: age, total prostate volume (TPV), transition zone volume (TZV), prostate specific antigen (PSA), maximum flow rate (Qmax), and post-void residual volume (PVR) on uroflowmetry, and International Prostate Symptom Score (IPSS). Among these variables, the independent predictors of BOO were selected using the CBN model. The predictive performance of the CBN model using the selected variables was verified through a logistic regression (LR) model with the same dataset. Results Mean age, TPV, and IPSS were 6.2 (±7.3, SD) years, 48.5 (±25.9) ml, and 17.9 (±7.9), respectively. The mean BOO index was 35.1 (±25.2) and 477 patients (34.5%) had urodynamic BOO (BOO index ≥40). By using the CBN model, we identified TPV, Qmax, and PVR as independent predictors of BOO. With these three variables, the BOO prediction accuracy was 73.5%. The LR model showed a similar accuracy (77.0%). However, the area under the receiver operating characteristic curve of the CBN model was statistically smaller than that of the LR model (0.772 vs. 0.798, p = 0.020). Conclusions Our study demonstrated that TPV, Qmax, and PVR are independent predictors of urodynamic BOO.