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Upper tract urothelial carcinoma (UTUC) is a rare tumor with an incidence that varies greatly between Eastern and Western countries. Transaldolase 1 (TALDO1) is a rate-limiting enzyme of the pentose phosphate pathway. In humans, aberrant TALDO1 activity has been implicated in various autoimmune diseases and malignancies; however, the function of TALDO1 in UTUC has not been previously investigated. Here we evaluated the clinical significance of TALDO1 expression in 115 paraffin-embedded tumor samples from patients with UTUC using immunohistochemistry. Our results demonstrated that there was an association between high TALDO1 expression and advanced stage (P = 0.011), tumor size (P = 0.005), tumor location (P = 0.047), distant metastases (P = 0.023), local recurrence (P = 0.002), and cancer death (P = 0.003). Using univariate and multivariate analyses, we found that chemotherapy was an independent factor for bladder recurrence-free survival. Late stage (III/IV) and high TALDO1 expression were independent prognostic factors for progression-free and cancer-specific survival. In summary, increased TALDO1 expression in UTUC was significantly correlated with late stage, tumor size, tumor location, distant metastases, local recurrence, and cancer death. Therefore, high TALDO1 expression could be a predictor of poor survival in patients with UTUC. Further studies are necessary to investigate the role of TALDO1 in UTUC development.

To study the relationship between oral disease and depressive symptoms in middle-aged and older adult populations in China.The data from the China Health and Retirement Longitudinal Study (CHARLS) done between 2013 and 2015 were analyzed. A total of 3828 middle-aged and older adults showing no depressive symptoms in an assessment with the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10) were selected as the subjects of observation, and oral disease was taken as the dependent variable. Changes in depressive symptoms in the population were tracked in 2015, and the Cox proportional hazards model was used to estimate the relationship between oral diseases and depressive symptoms.The detection rate of depressive symptoms was 29.3% in middle-aged and older adults with oral diseases, and that of middle-aged and older adults without oral diseases was 20.4%, the difference being statistically significant (Oral diseases in the middle-aged and older adult populations tended to lead to depressive symptoms, and women showed higher rate than men did. Prevention and control measures should be taken actively in the course of oral disease treatment to promote mental health of middle-aged and older adults.

CSN6 is a subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN). CSN is involved in cellular and developmental processes such as signal transduction, transcriptional activation, cell cycle control, and tumorigenesis. CSN6 is highly expressed in several human cancers, including colorectal cancer, and breast cancer. However, no previous research has elaborated on the relationship between CSN6 expression and survival in patients with upper tract urothelial carcinoma (UTUC). Therefore, the purpose of this study is to evaluate the clinical significance of CSN6 in UTUC. CSN6 expression in 89 patients with UTUC enrolled in this study was examined using immunohistochemistry. The associations between CSN6 expression and clinicopathological variables were analyzed. CSN6 expression was significantly correlated with patients with high pathological stage (P = .006), male gender (P = .025), and high serum creatinine levels (P = .014). In univariate and multivariable analysis, high CSN6 expression was associated with a higher bladder recurrence (P = .005) and poor cancer‐specific survival (P = .001) for UTUC. In conclusion, CSN6 expression is a potential biomarker for predicting cancer recurrence and clinical survival in UTUC. Further research is necessary to investigate its role in the progression of UTUC.

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Urothelial carcinoma (UC), including upper tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC), is a common malignant disease in developed countries. Oncogenic metabolic lesions have been associated with UC development. Methods: Using data mining, a series of studies were performed to study the involvement of SLC14A1 in UC specimens, animal models and UC-derived cell lines. Results: In two cohorts of UTUC (n = 340) and UBUC (n = 295), the SLC14A1 protein level was an independent prognostic factor. Epigenetic silencing contributed to SLC14A1 downregulation in UCs. Total and membranous SLC14A1 played tumor suppressive roles through the inhibition of cell proliferation and metastasis in distinct UC-derived cells and animal models. Functional SLC14A1 prevented the accumulation of arginine and urea, enhanced mitochondrial fusion and aerobic respiration, inhibited glycolysis by altering the expression levels of several related proteins and sensitized arginine-deprivation treatment in ASS1-deficient UC-derived cells. In vitro and in vivo, SLC14A1 inhibited the mTOR signaling pathway and subsequently tumorigenesis, supported by reduced arginine concentrations in vitro. Nuclear SLC14A1 transrepressed HK2 and DEGS1 genes via recruitment of HDAC1 and/or SIN3A to maintain metabolic homeostasis and thereafter impeded tumorigenesis. Conclusion: Clinical associations, animal models and in vitro indications provide solid evidence that the SLC14A1 gene is a novel tumor suppressor in UCs. Total and membranous SLC14A1 prevents urea and arginine accumulation via the mTOR signaling pathway. Nuclear SLC14A1 recruits HDAC1 to transrepress oncometabolite genes.

Polymerase I and transcript release factor (PTRF) has been implicated in cancer biology but its role in upper tract urothelial carcinoma (UTUC) is unknown. From a pilot transcriptome, we identified PTRF was significantly upregulated in high stage UTUC. Bladder cancer transcriptome from The Cancer Genome Atlas (TCGA) supported our finding and high PTRF level also predicted poor survival. We, therefore, investigated the correlation of PTRF with patients' clinicopathologic characteristics and outcomes in a multiracial UTUC cohort.By immunohistochemical staining, PTRF expression was determined using H-score. PTRF expression of 575 UTUCs from 8 institutions, including 118 Asians and 457 Caucasians, was compared with various clinicopathologic parameters. Human urothelial cancer cell lines were used to evaluate the level of PTRF protein and mRNA expression, and PTRF transcript level was assessed in fresh samples from 12 cases of the cohort. The impact of PTRF expression on disease progression, cancer-specific death and overall mortality was also examined.High PTRF expression was significantly associated with multifocality (P = 0.023), high pathologic tumor stage (P0.00001), nonurothelial differentiation (P = 0.035), lymphovascular invasion (P = 0.003) and lymph node metastasis (P = 0.031). PTRF mRNA expression was also markedly increased in advanced stage UTUC (P = 0.0003). High PTRF expressing patients had consistently worse outcomes than patients with low PTRF expression regardless of demographic variation (all P0.005). In multivariate analysis, high PTRF expression was an independent predictor for progression-free survival (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.07-2.69, P = 0.025), cancer-specific survival (HR 2.09, 95% CI 1.28-3.42, P = 0.003), and overall survival (HR 2.04, 95% CI 1.33-3.14, P = 0.001).Results indicate that PTRF is a predictive biomarker for progression and survival and an independent prognosticator of UTUC. Elevated PTRF could probably propel clinically aggressive disease and serve as a potential therapeutic target for UTUC.

BACKGROUND Long noncoding RNAs (lncRNAs) recently have been implicated in the pathological processes of cardiovascular diseases. In this study, LncRNADisease database and PubMed database were used to screen myocardial infraction (MI)-related lncRNAs and to investigate the diagnostic role of lncRNAs in ST-segment elevation myocardial infraction (STEMI). MATERIAL AND METHODS Forty-six patients with STEMI and 40 healthy controls were included in the study. Venous blood samples acquired at different time points and the expression levels of lncRNAs in plasma were measured by qRT-PCR. In addition, other blood samples were collected before and after percutaneous coronary intervention (PCI). Correlation analysis and receiver operating characteristic (ROC) curve were used to assess the diagnosis value of the markers. All included patients were followed up for 12±1 months. RESULTS Nine MI-related lncRNAs were selected from the database. The qRT-PCR results showed that the expression of hypoxia inducible factor 1A antisense RNA 2 (aHIF), member 1 opposite strand/antisense transcript 1 (KCNQ1OT1), and mitochondrial long noncoding RNA uc022bqs.1 (LIPCAR) were significantly increased in patients with STEMI compared to the control patients. The ROC curve showed that LIPCAR (AUC=0.782, 95% CI: 0.707-0.0.894) had better diagnostic accuracy. Moreover, correlation analysis indicated that LIPCAR were positively correlated with myocardial enzymes and negatively correlated with left ventricular ejection fraction. The level of LIPCAR in STEMI patients after PCI was lower (P

The relation of dialysis to tumor recurrence in patients with upper tract urothelial cancer (UTUC) is unknown; however, a limited number of small-scale studies suggest that patients with renal diseases prior to UTUC are more likely to exhibit bladder recurrence. We performed a population-based analysis to determine the effect of dialysis on bladder recurrence for patients with UTUC. This retrospective cohort study included patients diagnosed with UTUC (2002–2007) from the Taiwan National Cancer Registry and divided them into two groups—dialysis and non-dialysis groups. These patients were followed up until bladder recurrence, death, or the end of 2010. Competing risk analyses adjusting covariates and death were applied to determine the relation of dialysis and bladder recurrence. Of the 5141 eligible patients, 548 (10.7%) were undergoing dialysis. The cumulative bladder recurrence was significantly higher in the dialysis group than in the non-dialysis group (29% vs. 21%, modified log-rank p

Adrenergic receptors play a key role in activating the sympathetic nervous system, which often accompanies with the development of myocardial infarction (MI). Here, we aimed to test the association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with MI risk. Genotypes were available for 717 MI patients and 612 controls. There were no detectable deviations from the Hardy-Weinberg equilibrium for all study polymorphisms. Allele frequencies differed remarkably for ADRA2B D/I (P

// Hsiang-Ying Lee 1, 3, 4, 8 , Bi-Wen Yeh 3, 4 , Ti-Chun Chan 5, 6 , Kei-Fu Yang 2, 3 , Wei-Ming Li 2, 3, 4, 7 , Chun-Nung Huang 3, 4 , Hung-Lung Ke 3, 4 , Ching-Chia Li 3, 4, 8 , Hsin-Chih Yeh 2, 3, 4, 7 , Peir-In Liang 9 , Yow-Ling Shiue 6 , Wen-Jeng Wu 2, 3, 4, 8, 10, 11, 12 and Chien-Feng Li 5, 9, 11, 13, 14, 15 1 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 4 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan 6 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 7 Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan 8 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan 9 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 10 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 11 Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan 12 Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan 13 Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan 14 National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan 15 Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence to: Chien-Feng Li, email: angelo.p@yahoo.com.tw Wen-Jeng Wu, email: wejewu@kmu.edu.tw Keywords: urothelial carcinoma, transcriptome, SULF1, prognosis Received: November 25, 2016 Accepted: April 17, 2017 Published: May 03, 2017 ABSTRACT Urothelial carcinoma (UC), arising from the urothelium of the urinary tract, can occur in the upper (UTUC) and the urinary bladder (UBUC). A representative molecular aberration for UC characteristics and prognosis remains unclear. Data mining of Gene Expression Omnibus focusing on UBUC, we identified sulfatase-1 ( SULF1 ) upregulation is associated with UC progression. SULF1 controls the sulfation status of heparan sulfate proteoglycans and plays a role in tumor growth and metastasis, while its role is unexplored in UC. To first elucidate the clinical significance of SULF1 transcript expression, real-time quantitative RT-PCR was performed in a pilot study of 24 UTUC and 24 UBUC fresh samples. We identified that increased SULF1 transcript abundance was associated with higher primary tumor (pT) status. By testing SULF1 immunoexpression in independent UTUC and UBUC cohorts consisted of 340 and 295 cases, respectively, high SULF1 expression was significantly associated with advanced pT and nodal status, higher histological grade and presence of vascular invasion in both UTUC and UBUC. In multivariate survival analyses, high SULF1 expression was independently associated with worse DSS (UTUC hazard ratio [HR] = 3.574, P < 0.001; UBUC HR = 2.523, P = 0.011) and MeFS (UTUC HR = 3.233, P < 0.001; UBUC HR = 1.851, P = 0.021). Furthermore, depletion of SULF1 expression by using RNA interference leaded to impaired cell proliferative, migratory, and invasive abilities in vitro . In addition, we further confirmed oncogenic role of SULF1 with gain-of function experiments. In conclusion, our findings implicate the oncogenic role of SULF1 expression in UC, suggesting SULF1 as a prognostic and therapeutic target of UC.

We investigated the association of 4 well-characterized polymorphisms in receptor for the advanced glycation end-product ( RAGE) gene with myocardial infarction (MI) risk and the changes in metabolic risk factors among 717/612 patients/controls, with the aim of constructing a predictive nomogram. The genotype/allele distributions differed significantly between the 2 groups for T-429C ( Pgenotype/allele = .004/.001) and G1704T ( P < .001/.001). T-429C was significantly associated with MI risk, especially under a recessive model (adjusted odds ratio: 2.24, 95% confidence interval: 1.33-3.79, P = .003). For G1704T, significance was detected under additive (1.37; 1.12-1.67; P = .002) and recessive (3.86; 2.27-6.57; P < .001) models. There were significant differences in blood pressure and low-density lipoprotein cholesterol (LDL-C) across T-429C genotypes and in total cholesterol and LDL-C across G1704T genotypes. The overall best multifactor dimensionality reduction model included dyslipidemia, G1704T, and T-429C. Further predictive nomogram on 2 significant polymorphisms, blood pressure and lipids, showed a better predictive capability (concordance index = 0.716, P < .001). Altogether, we identified 2 polymorphisms of RAGE, T-429C and G1704T, which interacted with metabolic risk factors associated with the occurrence of MI. We also constructed a genetic–metabolic nomogram that can better predict MI risk.

Inconsistent prognostic implications of body mass index (BMI) in upper tract urothelial carcinoma (UTUC) have been reported across different ethnicities. In this study, we aimed to analyze the oncologic role of BMI in Asian and Caucasian patients with UTUC.We retrospectively collected data from 648 Asian Taiwanese and 213 Caucasian American patients who underwent radical nephroureterectomy for UTUC. We compared clinicopathologic features among groups categorized by different BMI. Kaplan-Meier method and Cox regression model were used to examine the impact of BMI on recurrence and survival by ethnicity.According to ethnicity-specific criteria, overweight and obesity were found in 151 (23.2%) and 215 (33.2%) Asians, and 79 (37.1%) and 78 (36.6%) Caucasians, respectively. No significant association between BMI and disease characteristics was detected in both ethnicities. On multivariate analysis, overweight and obese Asians had significantly lower recurrence than those with normal weight (HR 0.631, 95% CI 0.413-0.966; HR 0.695, 95% CI 0.493-0.981, respectively), and obesity was an independent prognostic factor for favorable cancer-specific and overall survival (HR 0.521, 95% CI 0.342-0.794; HR 0.545, 95% CI 0.386-0.769, respectively). There was no significant difference in outcomes among normal, overweight and obese Caucasians, but obese patients had a relatively poorer 5-year RFS, CSS, and OS rates of 52.8%, 60.5%, and 47.2%, compared to 54.9%, 69.1%, and 54.9% for normal weight patients.Higher BMI was associated with improved outcomes in Asian patients with UTUC. Interethnic differences could influence preoperative counseling or prediction modeling in patients with UTUC.

Background: Signal transducer and activator of transcription proteins (STATs) play important roles in gene regulation, cell proliferation, and cell differentiation. We aimed to establish the relationship between phosphorylated STAT3 (p-Ser-STAT3) expression and the prognosis of upper tract urothelial carcinoma (UTUC). Methods: This study retrospectively reviewed 100 patients with pathologically confirmed UTUC at Kaohsiung Medical University Hospital. We quantified the expression of p-Ser-STAT3 in cancer cells by immunohistochemistry, and determined the clinicopathological significance of p-Ser-STAT3 expression and prognostic outcomes in patients with UTUC. Results: High p-Ser-STAT3 expression was detected in 52% of UTUC patients. High p-Ser-STAT3 expression was associated with poor recurrence-free survival (p = 0.018) and overall survival (p = 0.026). In advanced cancer samples (stage T3/T4), p-Ser-STAT3 expression is the only independent prognostic factor for recurrence-free survival (hazard ratio = 5.91, p = 0.01) and cancer-specific survival (hazard ratio = 8.83, p = 0.039). Conclusions: The expression of p-Ser-STAT3 can be a potential prognostic marker for cancer recurrence and survival in UTUC, especially in advanced stage cases.

// Meng-Chen Tsai 1 , Wei-Ming Li 2, 3, 4, 5 , Chun-Nung Huang 3, 4 , Hung-Lung Ke 3, 4 , Ching-Chia Li 3, 4, 6 , Hsin-Chih Yeh 3, 4, 6 , Ti-Chun Chan 1 , Peir-In Liang 7 , Bi-Wen Yeh 3, 4 , Wen-Jeng Wu 2, 3, 4, 6, 8, 9, 10 , Sher-Wei Lim 11, 12, 13 , Chien-Feng Li 1, 14, 15, 16, 17 1 Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan 2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 4 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan 6 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan 7 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 8 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 9 Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan 10 Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan 11 Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan 12 Department of Neurosurgery, Chi-Mei Medical Center, Chiali, Tainan, Taiwan 13 Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan 14 Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan 15 National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan 16 Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 17 Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence to: Chien-Feng Li, email: angelo.p@yahoo.com.tw Sher-Wei Lim, email: slsw0219@gmail.com Keywords: urothelial carcinoma, transcriptome, DDR2, prognosis Received: September 20, 2016 Accepted: October 19, 2016 Published: October 26, 2016 ABSTRACT The migration ability of urothelial carcinoma corresponding to dismal prognosis had not been fully investigated. The interaction of extracellular collagen with a unique transmembrane receptor tyrosine kinase, Discoidin domain receptor 2 (DDR2), was selected by data mining. We arranged real-time reverse transcription polymerase chain reaction assays to evaluate the transcript levels in 26 urinary tract urothelial carcinoma and 26 urinary bladder urothelial carcinoma specimens, showing significantly increase corresponding to advanced primary stage ( p = 0.003 and p < 0.001, respectively). An immunohistochemistry analysis and H-score calculation were performed to determine DDR2 expression in 340 urinary tract urothelial carcinoma and 295 urinary bladder urothelial carcinoma. Assessments of the correlation to clinicopathologic features, disease-specific survival, and metastasis-free survival were conducted. The transcript levels in advanced stage were higher than those in early stage and were correlated with poor prognosis. The higher expression was positively correlated to higher pT status ( p < 0.001), higher histological grade (urinary tract, p = 0.041; urinary bladder, p < 0.001), greater vascular invasion ( p < 0.001), and higher mitotic rate (urinary tract, p = 0.039; urinary bladder, p < 0.001). Higher expression also indicates significantly worse disease-specific survival and metastasis-free survival. In vitro study revealed knockdown of DDR2 resulted in a depletion of cellular viability, migratory, and invasive ability, supporting the oncogenic function of DDR2.

Acute myocardial infarction (AMI) due to unprotected left main coronary artery (ULMCA) disease is clinically catastrophic although it has a low incidence. Studies on the long-term prognosis of these patients are rare.From January 1999 to September 2013, 55 patients whose infarct-related artery was the ULMCA were enrolled. Clinical, angiographic and interventional data was collected. Short-term and long-term clinical follow-up results as well as prognostic determinants during hospitalisation and follow-up were analysed.Cardiogenic shock (CS) occurred in 30 (54.5%) patients. During hospitalisation, 22 (40.0%) patients died. Multivariate logistic regression analysis showed that CS (odds ratio [OR] 5.86; p = 0.03), collateral circulation of Grade 2 or 3 (OR 0.14; p = 0.02) and final flow of thrombolysis in myocardial infarction (TIMI) Grade 3 (OR 0.05; p = 0.03) correlated with death during hospitalisation. 33 patients survived to discharge; another seven patients died during the follow-up period of 44.6 ± 31.3 (median 60, range 0.67-117.00) months. The overall mortality rate was 52.7% (n = 29). Kaplan-Meier analysis showed that the total cumulative survival rate was 30.7%. Cox multivariate regression analysis showed that CS during hospitalisation was the only predictor of overall mortality (hazard ratio 4.07, 95% confidence interval 1.40-11.83; p = 0.01).AMI caused by ULMCA lesions is complicated by high incidence of CS and mortality. CS, poor collateral blood flow and failure to restore final flow of TIMI Grade 3 correlated with death during hospitalisation. CS is the only predictor of long-term overall mortality.

Background. Colony-stimulating factor-1 (CSF-1) is a homodimeric glycoprotein. The main role of CSF-1 is as a hematopoietic growth factor that modulates proliferation, differentiation, and survival of macrophages. Moreover, CSF-1 has also been reported to be aberrantly expressed in several human cancers. However, the precise role of CSF-1 in upper tract urothelial carcinomas (UTUC) has not been studied. In this research, we examined the clinical significance of CSF-1 expression in UTUC. Materials and Methods. One hundred twelve cancer tissue samples of UTUC from patients were included in this study, and the other cohort of 35 UTUC were paired cancer-adjacent normal samples. CSF-1 expression was evaluated by immunohistochemistry, and the association of CSF-1 expression with different clinicopathological variables was analyzed. Results. CSF-1 expression was higher in UTUC than in the normal urothelium (P=0.005). The CSF-1 expression was primarily localized in the nucleus and was significantly correlated with tumor size (P=0.04) and patients who had a high stage (P<0.001), distant metastasis (P=0.006), recurrence (P=0.003), and cancer death (P=0.005). High CSF-1 expression was correlated with poor disease-free survival (P=0.008) and cancer-specific survival (P=0.001). Our results also used univariate and multivariable analyses, which found that high CSF-1 expression was an independent predictor of poor disease-free survival (hazard ratio=2.56; P=0.007) and cancer-specific survival (hazard ratio=5.14; P=0.022). Conclusions. Our findings indicate that the expression of CSF-1 is a potential prognostic marker for predicting patient survival and recurrence in UTUC.

Background Long-term outcomes of very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are still unclear. The aim was to evaluate the long-term outcomes after VLST of DES, and to analyze the related factors of long-term outcomes in these patients. Methods From January 2006 to February 2013, patients with angiographically defined VLST were studied. The clinical characteristics, angiography and interventional data, and anti-platelet therapy protocols were analyzed. The patients were divided into two groups according to the occurrence of major adverse cardiac events (MACE) during follow-up. The clinical and interventional data between the two groups were compared. Results Sixty-two patients were enrolled consisting of 55 males and 7 females with an average age of 58.6 ± 10.2 (41–82) years. The mean time from first implantation of DES to occurrence of VLST was 38.7 ± 18.1 (12.5–84) months. One patient died in hospital. Sixty-one patients survived to discharge, and MACE occurred in 17 patients after a median follow-up of 32.1 ± 19.1 (median: 44, range 5–88) months. The total MACE rate was 29.0% (18/62), and Kaplan–Meier survival analysis showed the estimated MACE-free survival was 45.1%. The rate of implantation of an additional first-generation DES during the first VLST in the group with events was higher (44.4% vs.11.4%, respectively, p = 0.007). The percentage of continuous dual antiplatelet therapy (DAPT) at the longest available follow-up was higher in the event-free group (27.8% vs. 75.0%, respectively, p = 0.001). Multivariable Cox regression analysis revealed that the only independent predictors for freedom of MACE during long-term follow-up was continuous DAPT at the longest available follow-up [hazard ratio (HR) = 0.30, 95% CI: 0.09–0.97, p = 0.04]. Conclusions Long-term outcomes after VLST were unfavorable. Implantation of an additional first-generation DES might be avoided, and DAPT should be continued.

Increasing evidence has shown that protein tyrosine phosphatases have dominant roles in setting the levels of tyrosine phosphorylation and promoting oncogenic processes. PTP4A3 has been implicated in cancer metastasis but to our knowledge the role of PTP4A3 in upper tract urothelial carcinoma is unknown. The aim of this study was to investigate the association of PTP4A3 with disease characteristics, distant metastasis and prognosis of upper tract urothelial carcinoma.The importance of PTP4A3 was initially examined in paired normal urothelium, noninvasive upper tract urothelial carcinoma, invasive upper tract urothelial carcinoma and nodal metastatic tissue. The PTP4A3 transcript level was assessed in another 20 upper tract urothelial carcinoma samples by real-time reverse transcriptase-polymerase chain reaction. PTP4A3 protein expression was determined by immunohistochemistry using the H-score in 340 upper tract urothelial carcinoma samples. It was further correlated with clinicopathological factors, and disease specific and metastasis-free survival.The expression of PTP4A3 significantly increased from normal urothelium, noninvasive upper tract urothelial carcinoma and invasive upper tract urothelial carcinoma to nodal metastatic tissue (p0.001). The PTP4A3 transcript level was also markedly up-regulated in higher stage upper tract urothelial carcinoma (p = 0.002). Over expression of PTP4A3 protein was significantly associated with advanced pT status, nodal metastasis, lymphovascular invasion and perineural invasion (each p0.001) as well as with inferior disease specific and metastasis-free survival on multivariate analysis (each p 0.0001). In addition, it predicted metastasis in patients with pTa, pT1 and pT2 upper tract urothelial carcinoma.Results imply that PTP4A3 has a role in the carcinogenesis of upper tract urothelial carcinoma. PTP4A3 over expression independently predicted the metastasis and outcome of upper tract urothelial carcinoma, which was even more important in organ confined disease.

Partial nephrectomy has gained wider acceptance as a surgical technique in treating small renal tumors. Laparoscopic partial nephrectomy (LPN) still remains a technically demanding surgery to this day. We present our technique of laparoscopic partial nephrectomy, one that is performed without intracorporeal suturing. We performed LPN on 31 patients with localized renal parenchymal tumor (stage T1). The procedures were done from September 2009 to March 2015 at the Kaohsiung Medical University Hospital and the Kaohsiung Municipal Ta-Tung Hospital. Our technique involves the covering of renal defect layer by layer with FloSeal, Tisseel and a fat pad after monopolar coagulation. Thirty-one patients were included in this study. Mean patient age was 53 years old (range 39–70). Mean tumor size was 2.9 cm (range 1.8–6.3). Mean RENAL nephrometry score was 5.3 (range 4–7). The average operation time was 188 min (range 120–290), and the average warm ischemic time was 19.0 min (range 9–26). Mean estimated blood loss was 171 ml (range 10–650), with no postoperative bleeding among the total 31 patients. No recurrent tumors were identified at a mean follow-up of 29 months postoperatively. The mean change in eGFR was 6.5 (ml/min/m2). Laparoscopic partial nephrectomy is a feasible surgical method for most patients with stage 1 tumor. Our technique has shown to reduce warm ischemic time significantly and provide patients with excellent functional outcomes without affecting oncological results. With this technique, surgeons can perform LPN with more efficiency and with fewer complications.

Background To clarify if diagnostic ureteroscopy (URS) before radical nephroureterectomy for patients with upper tract urothelial carcinoma (UTUC) will increase the risk of intravesical recurrence. Methods From retrospective review of cohort at our institution, 502 patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision were enrolled from 1990 to 2013. Cox proportional hazards model was used to analyze the overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and intravesical recurrence-free survival (IVRFS). The log-rank test was used for comparing survival curves. All potential risk factors were included in the multivariate Cox proportional hazards model to recognize independent predictors. From NHI database, we included patients of UTUC without bladder cancer history using population-based database in Taiwan from 1996 to 2013. In total, 3079 URS and 2634 non-URS patients with UTUC were identified. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of IVRFS and all-cause mortality. Results From our database, the comparison of clinicopathological characteristics in UTUC patients between with URS biopsy group (URS+) (n = 206, 41%) and without URS biopsy group (URS−) (n = 296, 59%) was insignificantly different excluding surgical method. URS biopsy is not associated with worse OS (p = 0.720), DFS (p = 0.294), MFS (p = 0.808), and IVRFS (p = 0.560) by multivariate analysis. Only bladder cancer history is an independent significant factor to predict IVR (p

This retrospective cohort study evaluated the association between gout and the risk of benign prostatic hyperplasia among men by using data from Taiwan’s National Health Insurance Research Database. Population-based representative insurance (outpatient and inpatient) claims data of 29,269 patients with gout and 29,269 matched patients without gout (1:1 ratio) for the period of 1997–2010 in Taiwan were identified. The association between gout and benign prostatic hyperplasia was evaluated using the Cox proportional hazards model. The associations of age by gout and gout phenotypes with benign prostatic hyperplasia risk were estimated. Patients with gout had a higher incidence rate of benign prostatic hyperplasia than those in the matched gout-free group (19.62 vs. 10.11 events per 1000 person-years). Compared with the gout-free group, the adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) for benign prostatic hyperplasia were 1.30 (1.24–1.36). The gout-to-benign prostatic hyperplasia association was modified by age (Pinteraction 60 years (adjusted HR 1.07, P = 0.063). Compared with gouty tophi, a higher risk of benign prostatic hyperplasia was noted in gouty nephropathy (adjusted HR 1.30, 95% CI 1.12–1.50). Our results suggest that male gout is positively related to benign prostatic hyperplasia, particularly in young gout patients and those with gouty nephropathy.

PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China’s registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2–4, the incidence of febrile neutropenia, and the safety. A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3–4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan–Meier analysis (n = 49, P = 0.153). PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Radical surgery (RS) with adjuvant chemotherapy (AC) or radiotherapy has been conventionally used for patients with advanced urothelial carcinoma (AUC). Recent research has indicated that systemic neoadjuvant chemotherapy (NC) with RS yields better outcomes than RS alone for patients with locally advanced bladder cancer. However, there are no reports indicating whether NC or AC would be beneficial for patients with AUC. The present study compared the survival rate for AUC patients receiving NC or AC. A retrospective analysis was conducted using data for 64 patients with AUC who underwent RS and systemic chemotherapy at our institution between March 2002 and March 2011. Of the 64 patients, 30 received NC before RS and 34 received RS followed by systemic AC. Pathologic stages (p=0.002), grades (p=0.018) and lymphovascular invasion (p=0.047) were significantly lower in the patients who received NC first than in those who received RC first. Furthermore, analysis of the surgical specimens revealed that 26.7% of patients who received NC before RS had complete remission. There were no significant differences in demographic data, surgical complications, and chemotoxicity between the two patient groups. The progression-free survival (PFS) and overall survival (OS) of patients who received initial NC were significantly better than those of patients who received initial RC (p=0.002 and 0.018, respectively). Our results indicate that NC administration before RS significantly improved the PFS and OS of AUC patients, without increasing surgical complications and chemotoxicity. Further prospectively controlled trials need to be conducted to confirm the effectiveness of NC for AUC patients.

The incidence of upper tract urothelial cancer (UTUC) has gradually increased over the past 30 years. Although most reports have shown that UTUC occurs more frequently in men than in women, women have been found to have a worse prognosis than men. In Taiwan, a high incidence of UTUC has been reported, with an unusual minor predominance of female cases. The purpose of this study was to determine the influence of gender on the outcome of patients with UTUC after nephroureterectomy and bladder cuff excision. From January 1990 to December 2007, 301 patients diagnosed with UTUC were admitted at our institution. A retrospective analysis of the effect of gender on the clinical outcome was performed. We compared the 5-year bladder recurrence-free, progression-free, and disease-specific survival rates. While we did not observe any differences between men and women in bladder recurrence-free, progression-free, or disease-specific survival rates, we found that female patients had a significantly higher percentage of contralateral recurrence than the males (5.9% vs. 0.8%, p = 0.019).

Background: Hypoxia has been shown to facilitate tumor progression. Hypoxia-regulated microRNA-210 (miR-210) may play an important role in carcinogenesis and tumor progression. In this study, we evaluated the clinical significance of miR-210 expression in upper tract urothelial carcinoma (UTUC). Methods: Eighty-three UTUC patients participated in this study. All of them provided cancer tissue samples and 50 of them provided non-cancerous urothelium samples. Clinicopathologic data were collected by reviewing medical records. The expression of miR-210 and hypoxia-inducible factor-1α (HIF-1α) was determined by quantitative real-time polymerase chain reaction. The relationship between clinicopathologic variables and the expression of miR-210 and HIF-1α was analyzed statistically. Results: MiR-210 is overexpressed in UTUC compared to non-cancerous urothelium (p < 0.001); it is also upregulated in high-stage and high-grade tumors (p = 0.020 and 0.049, respectively). HIF-1α is overexpressed in UTUC and correlates positively with miR-210 expression (r = 0.442, p = 0.001). Conclusion: Both miR-210 and HIF-1α are involved in promoting UTUC carcinogenesis. MiR-210 is also correlated with tumor progression. Further studies are needed to clarify the underlying mechanism.

Introduction In addition to a depletion of androgen, attenuated action of androgen receptor (AR) might also contribute to andropausal symptoms. Aim To evaluate the interaction of AR cytosine adenine guanine (CAG) repeat polymorphism and serum testosterone levels and their effect on andropausal symptoms in aging Taiwanese men. Methods From August 2007 to April 2008, a free health screening for men older than 40 years was conducted by a medical center in Kaohsiung City, Taiwan. All participants received physical examination, answered questionnaires to collect their demographic information and medical histories, completed the Androgen Deficiency in the Aging Male (ADAM) questionnaire, and provided 20‐cm3 whole blood samples for biochemical and genetic evaluation. Main Outcome Measures The ADAM questionnaire was used to evaluate andropausal symptoms. Serum albumin, total testosterone (TT), and sex hormone‐binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Results Seven hundred two men with the mean age of 57.2 ± 6.5 years were included. There was no significant association between TT levels and the distribution of AR CAG repeat polymorphism. When TT levels were above 340 ng/dL, subjects with AR CAG repeat lengths ≧25 showed significantly higher risk of developing andropausal symptoms, as compared with those with AR CAG repeat lengths ≦22 (P = 0.006), but this was not observed when TT levels were 340 ng/dL or below. Age and number of comorbidities were also independent risk factors for andropausal symptoms. Conclusion In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing andropausal symptoms. Age and number of comorbidities can also influence the appearance of andropausal symptoms. In clinical practice, a multifactorial approach to evaluate andropausal symptoms and the interactions between those risk factors is suggested. Liu C‐C, Lee Y‐C, Wang C‐J, Yeh H‐C, Li W‐M, Wu W‐J, Huang C‐N, Bao B‐Y, Huang C‐H, and Huang S‐P. The impact of androgen receptor CAG repeat polymorphism on andropausal symptoms in different serum testosterone levels. J Sex Med 2012;9:2429–2437.

The prevalence of androgen deficiency in men increases with aging. Two common instruments, the Aging Male Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire, are often used to screen for androgen deficiency in clinical practice. The aim of this study is to compare the capability of the AMS scale and the ADAM questionnaire to detect androgen deficiency in middle-aged Taiwanese men. In April 2008, a free health screening was conducted by Kaohsiung Medical University Hospital. All participants completed a health questionnaire and had blood samples drawn between 8:00 am and noon. Serum total testosterone (TT), albumin, and sex hormone-binding globulin levels were measured. The level of free testosterone (FT) was calculated. Clinical symptoms associated with androgen deficiency were screened by using the AMS scale and ADAM questionnaire. Androgen deficiency was defined as TT < 300 ng/dL or both TT < 300 ng/dL and FT< 5 ng/dL. In total, 339 men were included in the final analysis, with the mean age of 54.6 ± 4.9 years (range, 47-65 years). Androgen deficiency was found in 75 men (22.1%) based on the criteria of TT < 300 ng/dL, and in 54 men (15.9%) based on the criteria of TT < 300 ng/dL and FT < 5 ng/dL. When detecting participants with both TT < 300 ng/dL and FT < 5 ng/dL, the sensitivity and specificity of the AMS scale were 57.4% and 48.1%, compared with 66.7% and 25.6% for the ADAM questionnaire. In a sample of middle-aged Taiwanese men, neither the AMS scale nor the ADAM questionnaire had sufficient sensitivity and specificity to detect androgen deficiency. In addition to using those 2 screening instruments, a thorough physical and biochemical workup should still be conducted in patients at risk or suspected of androgen deficiency.

Recently, metabolic syndrome (MtS) has received increasing attention. However, investigations regarding the potential impact of MtS and its components on erectile dysfunction (ED) have not been completely clarified.To determine the potential impact of MtS on ED in aging Taiwanese males.The definition of MtS was according to the modified criteria developed by the Bureau of Health Promotion in Taiwan. The presence and severity of ED were evaluated by International Index of Erectile Function 5 (IIEF-5) scores.A total of 639 subjects with a mean age of 60.2 years (range 40-83) were enrolled during a free health screening. All the men had complete clinical data and questionnaires taken. Clinical variables were compared according to MtS and ED prevalence. Multiple logistic regression analysis was used to determine the independent predictors of ED and MtS.Using age-adjusted multivariate logistic regression analysis, our results showed that subjects with ED had significantly higher prevalence of MtS (P0.01, OR=2.30, 95% CI: 1.44-3.69). The presence of MtS had significant correlation with lower IIEF-5 scores (P0.01), which were associated with the increment of MtS components number (P0.01). Among the MtS components, abnormal fasting blood glucose (FBG) was the most significantly independent factor of MtS for ED (P=0.01, OR=1.60, 95% CI: 1.09-2.35). Testosterone levels were significantly lower in subjects with MtS (P=0.05), while inversely correlated with number of MtS components (P0.01).In aging Taiwanese males, the presence of MtS is strongly associated with ED and abnormal FBG is the most independent predictor for ED. Low testosterone level might be viewed as another possible common denominator for various pathologies linking MtS to ED.

This study assessed the possible associations between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in aging Taiwanese males and investigated the impact of various aspects of LUTS on ED.A free health screening for aging males (or =40 years old) was conducted in Kaohsiung Medical University Hospital. All the subjects had completed clinical data and answered questionnaires. ED and LUTS were assessed by validated symptom scales: the International Index of Erectile Function-5 (IIEF-5) and the International Prostate Symptom Score (IPSS).A total of 339 eligible patients enrolled in this study with a mean age of 60.1 years old. In multiple logistic regression analysis, age and IPSS (p0.001 and p = 0.013, respectively) were significantly associated with ED after controlling other comorbidities. In a further age-adjusted multiple regression analysis, our results showed that irritative symptoms (p = 0.042) have a more significant association with ED than the obstructive symptoms (p = 0.101).Our results indicate that age and LUTS are the two most independent risk factors for ED. Aging Taiwanese males with LUTS are at increasing risk for ED, especially for those with significant irritative symptoms.

Introduction A number of literature has now identified the role of impaired nitric oxide synthase/nitric oxide pathway in the endothelium as the central to the development of erectile dysfunction (ED) and benign prostate hyperplasia‐related lower urinary tract symptoms (BPH/LUTS). Recently a few studies have reported the associations between endothelial nitric oxide synthase ( eNOS ) G894T gene polymorphisms and ED. However, there has been no report investigating the eNOS G894T genetic susceptibility factor for both ED and BPH/LUTS. Aim To investigate the possible associations among eNOS G894T polymorphism, ED, and BPH/LUTS in a Taiwanese population. Main Outcome Measures Patients with ED were defined as those having a 5‐item International Index of Erectile Function‐5 Methods In all, 372 Taiwanese men underwent a free health screening were enrolled. All the men had complete clinical data and questionnaires taken. The eNOS G894T polymorphisms were determined using the polymerase chain reaction‐restriction fragment length polymorphism method. Results Three hundred seventy‐two men had a mean (standard deviation) age of 60.2 (8.8) years. With multivariate analysis, our data identified that aging, diabetes mellitus (DM), and eNOS G894T gene polymorphism were three independent common risk factors for both ED and BPH/LUTS ( P P = 0.036, and P = 0.039 for ED; P = 0.034, P = 0.004, and P = 0.016 for BPH/LUTS, respectively). The eNOS 894T allele carriers had significantly higher prevalence of ED (77.9% vs. 60.4%, P = 0.012) and higher International Prostate Symptom score (IPSS) (13.3 ± 10.7 vs. 9.3 ± 7.8, P = 0.001) than G allele carriers. Conclusions Our results showed that aging, DM, and eNOS 894T allele carrier gene polymorphism were the three independently common risk factors for both ED and BPH/LUTS in the Taiwanese population. The eNOS 894T allele carriers had significantly higher frequencies of ED and higher IPSS, suggesting that eNOS G894T gene polymorphisms may play an implication as a genetic susceptibility factor for both ED and BPH/LUTS. Lee YC, Wu WJ, Liu CC, Wang CJ, Li WM, Huang CH, Yeh HC, Ke HL, and Huang SP. The associations among eNOS G894T gene polymorphism, erectile dysfunction, and benign prostate hyperplasia‐related lower urinary tract symptoms.

Ezrin, a member of the ezrin–radixin–moesin family, acts as a link between the cell membrane and actin cytoskeleton to integrate cell adhesion-mediated signaling. It implicates tumor progression, metastatic dissemination, and adverse outcomes in several cancer types, including pediatric and adult sarcomas. Although ezrin upregulation was shown by cDNA expression profiling, no study has systematically evaluated the significance of ezrin expression in a large cohort of gastrointestinal stromal tumors (GISTs). Ezrin immunostaining was carried out on tissue microarrays of primary GISTs and assessable in 347 cases, 188 of which were successfully evaluated for mutation variants of KIT and PDGFRA receptor tyrosine kinase (RTK) genes by sequencing with or without screening by denatured high-performance liquid chromatography. These GISTs with known RTK genotypes were dichotomized into two prognostically different groups. The endogenous expression and phosphorylation of ezrin in GIST cell lines were analyzed by western blotting. By immunohistochemistry, ezrin overexpression was present in 66% of GISTs and significantly associated with the non-gastric location (P=0.002) and decreased disease-free survival (P=0.032, univariately). However, it was not related to the National Institute of Health (NIH) risk category, Ki-67 labeling index, RTK genotypes, and other variables. In multivariate analyses, ezrin overexpression remained independently predictive of adverse outcome (P=0.008, risk ratio=2.363), together with Ki-67 labeling index >5% (P

We studied the long-term prognosis, and evaluated the predictors of disease specific and recurrence-free survival in a large cohort of patients who had undergone radical nephroureterectomy for primary transitional cell carcinoma of the ureter.From January 1990 to December 2006, 145 patients with primary ureteral transitional cell carcinoma treated with nephroureterectomy and bladder cuff removal at our institution were included in the study. The medical records of these patients were reviewed retrospectively. The clinical and histopathological data were analyzed to evaluate the prognostic predictive factors. Univariate and multivariate statistical analyses were performed.The 5-year disease specific survival rates of stage pTa/Tis/T1, pT2, pT3 and pT4 were 94.6%, 81.8%, 47.4% and 0%, respectively. The 5-year recurrence-free survival rates according to tumor grade were 68.4% for low grade and 35.7% for high grade disease. Of the 145 patients subsequent bladder tumors developed in 38 (26.2%), local recurrence developed in 11 (7.6%) and metachronous contralateral upper urinary tract tumor developed in 3 (2.1%). Most patients had subsequent tumor recurrence within the first year after radical surgery. On univariate and multivariate analyses tumor stage, tumor grade, severity of chronic renal disease, synchronous bladder tumor and hematuria were the significant prognostic variables predicting disease specific and recurrence-free survival.Advanced tumor and chronic renal disease stages were significantly associated with a worse prognosis in patients with primary ureteral transitional cell carcinoma who had undergone radical nephroureterectomy. With regard to tumor recurrence, advanced tumor stage, high tumor grade and synchronous bladder tumor were independent risk factors.

Androgen deficiency in aging men has attracted much medical interest. Most studies on androgen deficiency have been conducted in Caucasian populations, and data from other ethnicities are lacking.To evaluate the prevalence of and risk factors for androgen deficiency and symptomatic androgen deficiency in Taiwanese men over 40 years old.From August 2007 to April 2008, a free health screening was conducted by a medical center in Kaohsiung, Taiwan, and 819 men participated in this health screening. All participants completed a health questionnaire, received a detailed physical examination, and blood samples were drawn between 8:00 and 12:00 am.Serum total testosterone (TT), albumin, and sex hormone-binding globulin levels were measured. The level of free testosterone (FT) was calculated. Clinical symptoms of androgen deficiency were assessed using the Androgen Deficiency in the Aging Male (ADAM) questionnaire.Seven hundred thirty-four men who met the inclusion criteria (mean age 57.4 +/- 6.7 years; range: 43-87 years) were included in this study. The prevalence of androgen deficiency was 24.1% based on the criterion of TT level300 ng/dL, and 16.6% based on the criterion of both TT300 ng/dL and FT5 ng/dL. The prevalence of symptomatic androgen deficiency was 12.0%. Both prevalence of androgen deficiency and symptomatic androgen deficiency increased with age. Older age, obesity, and diabetes mellitus were independent risk factors for androgen deficiency and symptomatic androgen deficiency.In a sample of aging Taiwanese men, a substantial proportion had androgen deficiency and symptomatic androgen deficiency, and the prevalence increased with age. Older age, obesity, and diabetes mellitus were independent risk factors for androgen deficiency and symptomatic androgen deficiency. Those potentially modifiable risk factors like obesity and diabetes mellitus should be prevented to maintain normal testosterone levels during aging in men.

Aim: The aim of this study was to evaluate the clinical characteristics of uric acid urolithiasis and how the presentation differs between urolithiasis of the upper urinary tract (UUT) compared with urolithiasis of the bladder. We attempted to evaluate the importance of local vs. systemic factors in the formation of bladder uric acid stones. Patients and Methods: The medical records of 77 consecutive patients with uric acid urolithiasis from January 2004 to December 2006 were reviewed retrospectively. In all patients, histories were recorded, and physical examinations, renal function tests and urine analysis were done. The features of the treated stones were recorded, and the chemical composition was analyzed by computed Fourier transform infrared spectrophotometry. Results: Among 77 patients with uric acid stones, 66 were male and 11 were female (ratio of 7.6:1). Mean age was 59.50 ± 10.46 years. Of the stones, 55 (71.4%) were located in the UUT (UUT group) and 22 (28.6%) in the bladder (bladder group). Multiple presentations of urolithiasis at diagnosis were found in 56 (72.7%) patients. The mean values of serum creatinine and uric acid were 148.28 ± 70.69 and 443.33 ± 95.91 μmol/l, respectively. Mean body mass index (BMI) was 26.78 ± 2.90, and 72.7% of patients were overweight or obese. Mean urinary pH was 5.39. No significant differences existed between the 2 groups in regard to gender, BMI, urinary pH, stone nature, or presence of hypertension, gout, and/or urinary tract infections. In the bladder group, the incidence of benign prostate hyperplasia was significantly increased, and the incidence of diabetes mellitus was significantly lower, as were levels of serum uric acid and creatinine. Conclusions: Uric acid urolithiasis was predominant in men in this study. These patients tended to be obese or overweight, with multiple stone presentations and low urinary pH. Furthermore, the bladder uric acid stone group had significantly lower levels of serum creatinine and uric acid, and lower percentages of diabetes mellitus but higher incidences of benign prostate hyperplasia in comparison with the UUT group. The local factor seems more important than the systemic factor in the formation of bladder uric acid stone.

Priapism is a prolonged penile erection that is not associated with sexual stimulation. Although the time course has not been formally defined, it is usually considered to be one that lasts for more than 4–6 hours. Low-flow (ischemic) priapism is usually associated with sickle cell disease, hemoglobinopathies, neoplastic syndrome, anticoagulant therapy, psychotropic medication or idiopathic causes. Here, we report a case of prolonged low-flow priapism lasting for 2 weeks, which was successfully treated with the Winter procedure after several attempts of conservative treatment. Although the potency remains unclear and the patient needs a longer period of follow-up, the case reported here still shows that prolonged low-flow priapism can be successfully treated with the Winter procedure when conservative treatments fail.

Background Recent studies have showed that the fine mesh stents are associated with a significant reduction in both clinical and angiographic re-stenosis of the coronary arteries.To maintain a very satisfactory radio-opacity using the stents,Guidant of the USA has designed a new type of bare metal stents (BMS)-Multi-link (ML) Vision/ML MiniVision stents.The clinical outcomes of Asian patients with coronary artery disease (CAD) after implanting the Multi-link Vision or MiniVision stent were investigated in this study. Methods An observational,prospective,multi-center,non-randomized post marketing registry was conducted to demonstrate the efficacy of the BMS- ML Vision/ML MiniVision stents.The primary end point of the registry was clinical target lesion revascularization (TLR) at a 6-month follow-up.The major secondary end points included the rate of major adverse cardiac events (MACE) and serious adverse events (SAE) in hospital and at 6 months;and the rate of clinical TLR as a function of the type of angina.A total of 429 Asian people with 449 lesions from 14 centers were selected for this study.The average reference diameter of the lesions was (3.0±0.5) mm,and the mean length was (15.7±5.0) mm. Results The successful rate of the procedure was 99.3%.Twenty-five percent of the lesions were treated by direct stenting without pre-dilation.Eighty-six percent of the lesions were implanted with ML Vision stent.After the 6-month follow-up,the rate of clinical TLR was 1.4%.The MACE,SAE and target vessel revascularization (TVR) were 6.8%,3.5% and 1.4% respectively. Conclusion The current registry showed the excellent 6-month clinical outcomes of ML Vision/ML MiniVision stents in Asian patients with CAD. Chin Med J 2007;120(12):1093-1096

Uric acid urolithiasis develops from various causes. To investigate the clinical and biochemical presentation of patients with uric acid urolithiasis, a retrospective study was designed. A total of 46 cases were enrolled between January 2004 and December 2005. The compositions of the stones were analyzed by infrared spectrophotometry. There were 39 males (84.8%) and seven females (15.2%), with a mean age of 61.5 +/- 10.6 years and mean body mass index (BMI) of 26.7 +/- 3.1 kg/m2. The stone location was kidney in 10 (21.7%), ureter in 22 (41.8%), and bladder in 14 (30.5%). Multiple stones were diagnosed in 36 patients (78.3%). Pre-existing comorbidities included diabetes mellitus in 11 patients (23.9%), hypertension in 23 (50%), gout in 13 (28.2%), and benign prostatic hyperplasia in 14 (30.4%). Mean serum creatinine and uric acid was 1.6 +/- 0.6 mg/dL and 7.6 +/- 1.8 mg/dL, respectively. There were 27 patients (58%) with creatinine1.4 mg/dL. The mean urinary pH was 5.42 +/- 0.46. Patients with uric acid urolithiasis were predominantly male, older, with higher BMI, multiple stone presentation, with lower urinary pH, and hyperuricemia. Exacerbation of the renal function should also be of concern because of the high proportion of patients with renal insufficiency diagnosed in this study.

Radical cystectomy with ileal conduit diversion remains the standard treatment for invasive bladder cancer. We report a patient with urothelial carcinoma of the urinary bladder and found metastasis to the orbit post radical cystectomy and ileal conduit diversion presenting as blurred vision and diagnosed by open biopsy. The orbit is an infrequent site of metastasis from bladder cancer cells. To the best of our knowledge, there are fewer than 10 case reports of orbital metastasis from urothelial carcinoma reported in the English medical literature.

Urolithiasis is a common urologic disease. Stones may occur in the kidney, ureter, or urinary bladder. We collected 1,000 stone samples in the subtropical area of southern Taiwan. Stone components were analyzed by Fourier transform infrared spectroscopy. Mixed components of calcium oxalate and calcium phosphate were the most common form of stones (52.3%), followed by calcium oxalate (27.8%) and calcium phosphate (9.3%). Uric acid stones accounted for 7.6%. Magnesium ammonium phosphate stones accounted for 3.0%. Only one cystine stone was found. In the study of urinary stone formation mechanism and prevention of recurrent urolithiasis, knowing the stone composition is important.

Aim: To determine efficacy and clinical predictors of stone fragmentation when using slow-rate shock wave lithotripsy (SWL). Patients and Methods: In total, 116 patients with radiopaque urinary tract stones were randomized into two groups: 57 patients were treated with SWL at 90 shocks/min, and 59 patients were treated with SWL at 120 shocks/min. The efficacy of SWL was evaluated within 1 month after treatment. Patient characteristics, features of stones, and SWL conditions were reviewed. Success rates relating to individual parameters were assessed by using chi-square and Student t tests. All factors were further entered into multivariate logistic regression analysis. Results: There were no statistically significant differences between the two groups with regard to age, sex, site and size of the stones, renal function, and total number of shock waves. In univariate analysis, the success rate was significantly related to shock wave frequency (p = 0.023), length and width of the stones (p < 0.001), total number of shock waves (p = 0.047), and age (p = 0.049). In multivariate analysis, however, only shock wave rate and stone length remained statistically significant (p = 0.021 and p = 0.046, respectively). The overall success rate was significantly higher in the group treated with 90 shocks/min (p = 0.02). However, this higher success rate was statistically significant only in patients with a stone length ≧10 mm (50.0 vs. 18.5%, p = 0.019). Conclusion: SWL at 90 shocks/min yielded better outcomes than SWL at 120 shocks/min, particularly in patients with stone lengths ≧10 mm.

Urothelial carcinomas (UC) of urinary bladder (UB) and upper urinary tract (UT) are heterogeneous diseases with high morbidity and mortality. We looked for genes with metalloendopeptidase activity in a published UBUC transcriptomic database (GSE31684):MMP-11 was the most significant, showing stepwise up-regulation. We analyzed MMP-11 expression and association with clinicopathologic factors and survival in our well-characterized cohort of UCs.We determined MMP-11 expression in 295 UBUCs and 340 UTUCs with immunohistochemistry, evaluated by H-score. In a retrospective study, MMP-11 expression was correlated with clinicopathologic features and with disease-specific survival (DSS) and metastasis-free survival (MeFS). The statistical significance was evaluated with univariate and multivariate analyses.High MMP-11 expression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular and perineural invasion, and frequent mitoses. In multivariate Cox regression analyses, which adjusted for standard clinicopathologic characteristics, MMP-11 expression was independently associated with cancer-specific mortality (hazard ratio [HR] in UTUC:3.027, P = 0.005; in UBUC: 2.631, P = 0.010) and with metastasis development (HR in UTUC:2.261, P = 0.018; in UBUC:1.801, P = 0.026).MMP-11 overexpression is associated with aggressive tumor phenotype and unfavorable clinical outcome in UTUC and UBUC, suggesting it may serve as a novel prognostic and therapeutic target. J. Surg. Oncol. 2016;113:700-707. © 2016 Wiley Periodicals, Inc.

BackgroundThe protein anillin (ANLN) has important roles in cell cytokinesis. Until now, no studies have evaluated the role of ANLN expression in a large cohort of patients with urothelial carcinoma of the upper urinary tract (UCUT).MethodsThis study analysed 156 cases of primary localised UCUT. Pathological slides were reviewed and clinical findings were collected. An immunohistochemical study was performed and the cytoplasmic and nuclear staining results of UCUT were recorded. Expressions of ANLN were analysed to identify correlations with various clinicopathological parameters, disease-specific survival (DSS) and metastasis-free survival (MeFS).ResultsOverexpression of ANLN in the nucleus had significant positive associations with tumour stage (p=0.017), histological grade (p=0.040), mitotic count (p=0.023), tumour necrosis (p=0.009), invasion patterns (pConclusionsSubcellular localisation of ANLN is correlated with different tumour phenotypes and probably confers different tumorigenicity. Since high nuclear expression of ANLN is also an independent predictor of poor DSS, it is a useful prognostic marker of UCUT.

Urothelial carcinoma of the bladder and upper tract is the most common tumor type in the urinary tract but its molecular pathogenesis and survival determinants remain obscure. By data mining a published transcriptomic database of bladder urothelial carcinoma (GSE31684) we identified FGF7 as the most significant gene up-regulated during urothelial carcinoma progression. We then used our well characterized urothelial carcinoma cohort to analyze FGF7 transcript and protein expression, and its clinicopathological significance.We performed real-time reverse transcriptase-polymerase chain reaction assay to determine the FGF7 transcript level in 30 fresh samples each of upper tract and bladder urothelial carcinoma. Immunohistochemistry evaluated by H-score was used to determine FGF7 protein expression in 340 upper tract and 295 bladder urothelial carcinomas. Transcript and protein expression were correlated with clinicopathological features. We further evaluated the prognostic significance of FGF7 protein expression for disease specific and metastasis-free survival.An increased FGF7 transcript level was associated with higher pT stage in upper tract and bladder urothelial carcinoma (p = 0.003 and0.001, respectively). In the upper tract and bladder carcinoma groups FGF7 protein over expression was also significantly associated with advanced pT status (each p0.001), lymph node metastasis (p = 0.002 and0.001), high histological grade (p = 0.019 and0.001), vascular invasion (each p0.001), perineural invasion (p = 0.002 and 0.021) and frequent mitoses (p = 0.002 and 0.042, respectively). FGF7 over expression predicted dismal disease specific and metastasis-free survival on univariate and multivariate analysis.Our study shows that FGF7 over expression is associated with advanced clinical features in patients with upper tract and bladder urothelial carcinoma, justifying its potential prognostic value for urothelial carcinoma.

// Chien-Feng Li 1, 2, 3, * , Wen-Jeng Wu 4, 5, 6, 7, * , Wen-Ren Wu 8 , Yu-Jing Liao 9 , Lih-Ren Chen 3, 9 , Chun-Nung Huang 6, 7, 8 , Ching-Chia Li 6, 7, 10 , Wei-Ming Li 4, 5, 7, 11 , Hsuan-Ying Huang 12 , Yi-Ling Chen 8 , Shih-Shin Liang 8, 13 , Nan-Haw Chow 14, 15 , Yow-Ling Shiue 8, 16, 17 1 Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan 2 National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan 3 Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan 4 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 7 Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan 8 Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan 9 Division of Physiology, Livestock Research Institute, Tainan, Taiwan 10 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan 11 Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan 12 Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan 13 Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan 14 Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan 15 Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan, Taiwan 16 Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan 17 Doctoral degree program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Yow-Ling Shiue, e-mail: ylshiue@mail.nsysu.edu.tw Keywords: EMP2, CREB1, urinary bladder urothelial carcinoma, tumor suppressor Received: October 20, 2014 Accepted: February 08, 2015 Published: April 13, 2015 ABSTRACT In this study, we report that EMP2 plays a tumor suppressor role by inducing G 2 /M cell cycle arrest, suppressing cell viability, proliferation, colony formation/anchorage-independent cell growth via regulation of G 2 /M checkpoints in distinct urinary bladder urothelial carcinoma (UBUC)-derived cell lines. Genistein treatment or exogenous expression of the c AMP r esponsive e lement b inding protein 1 ( CREB1 ) gene in different UBUC-derived cell lines induced EMP2 transcription and subsequent translation. Mutagenesis on either or both cAMP-responsive element(s) dramatically decreased the EMP2 promoter activity with, without genistein treatment or exogenous CREB1 expression, respectively. Significantly correlation between the EMP2 immunointensity and primary tumor, nodal status, histological grade, vascular invasion and mitotic activity was identified. Multivariate analysis further demonstrated that low EMP2 immunoexpression is an independent prognostic factor for poor disease-specific survival. Genistein treatments, knockdown of EMP2 gene and double knockdown of CREB1 and EMP2 genes significantly inhibited tumor growth and notably downregulated CREB1 and EMP2 protein levels in the mice xenograft models. Therefore, genistein induced CREB1 transcription, translation and upregulated pCREB1(S133) protein level. Afterward, pCREB1(S133) transactivated the tumor suppressor gene, EMP2 , in vitro and in vivo . Our study identified a novel transcriptional target, which plays a tumor suppressor role, of CREB1.

OBJECTIVE: The aim of this study was to compare the 2-year clinical outcomes of overlapping second-generation everolimus-eluting stents (EES) with those of overlapping resolute zotarolimus-eluting stents (R-ZES) in the treatment of long coronary artery lesions. MATERIALS AND METHODS: This retrospective analysis included 256 patients treated with overlapping EES (n=121) and R-ZES (n=135) for long coronary artery lesions (total stent length per lesion ≥34 mm). Study endpoints included major adverse cardiac events (MACE) defined as the composite of cardiac death, myocardial infarction, and target-vessel revascularization (TVR), as well as target-lesion revascularization and definite stent thrombosis separately at 2 years. RESULTS: In the two groups, the mean age was older and the average number of disease vessel was higher in the R-ZES group. The mean lesion length and total stent length per lesion were longer in the R-ZES group. EES were more frequently implanted in the left anterior descending coronary artery. No significant differences in the estimated MACE (5.8% for EES vs. 8.1% for R-ZES; P=0.548) or TVR (3.4% for EES vs. 4.0% for R-ZES; P=0.806) rates were noted between the two groups at 2-year follow-up. The incidence of definite stent thrombosis was low and similar in both groups (0.83% for EES vs. 0% for R-ZES; P=0.473). No significant differences were noted with respect to MACE or TVR between the two groups following propensity score matching. CONCLUSION: Stent overlap with second-generation EES or R-ZES was associated with low rates of MACE, TVR, and stent thrombosis at 2-year follow-up. Our results suggest that the use of overlapping EES or R-ZES in long coronary lesions is associated with good long-term clinical outcomes. These results need to be validated with randomized controlled trials.

Upper urinary tract (pyelocalyceal cavities and ureter) urothelial carcinoma is a relatively rare neoplastic disease. Although diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in urothelial carcinoma progression we performed bioinformatics guided experimental investigation targeting chromosome 19q13.We investigated the effects of EMP3 on cancer cell growth, migration and adhesion in transfection and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was examined by reverse transcriptase-polymerase chain reaction and immunoblot. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation specific polymerase chain reaction. To validate clinical relevance we measured EMP3 expression at the mRNA and protein levels in a cohort of 77 patients with upper urinary tract urothelial carcinoma and compared prognostic significance in relation to that of ErbB2 expression.We noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression promoted cancer cell proliferation and migration but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2 and EMP3 co-expression was the most important indicator of progression-free and metastasis-free survival in patients with upper urinary tract urothelial carcinoma (log rank test p = 0.018 and 0.04, respectively).EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy.

The role of alprostadil and statins in contrast-induced acute kidney injury (CI-AKI) is controversial. The purpose of this study was to explore the efficacy of combined therapy with alprostadil and statins in protecting renal function and preventing contrast-induced nephropathy (CIN) in patients undergoing coronary angiography.A total of 156 consecutive patients with mild to moderate renal failure who underwent coronary angiography were enrolled in our study, and randomly categorized into two groups. In the statins group, 80 patients were treated with statins before and after coronary angiography. In the alprostadil plus statins group, 76 patients were treated with statins and alprostadil before and after coronary angiography. Serum creatinine (SCr), serum cystatin (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) were detected after administration of contrast media, and adverse events were evaluated within six months.In both groups, the SCr, CysC and NGAL significantly increased after coronary angiography and peaked at 48, 24 and 6 hours, respectively. SCr, CysC and NGAL were significantly lower in the alprostadil plus statins group than in the statins group (P0.05). The incidence of CIN in the alprostadil plus statins group was slightly lower than in the statins group. The incidence of adverse events within six months in the alprostadil plus statins group was significantly lower than in the statins group (P = 0.034).Intravenous alprostadil in combination with oral statins is superior to statins alone for protecting renal function in patients with mild to moderate renal dysfunction who undergo coronary angiography, and can reduce the incidence of adverse events seen within six months.

Upper urinary tract urothelial carcinoma is a relatively uncommon disease and is diagnosed more frequently at advanced stages. The prognosis of these patients mainly has been related to tumor stage and grade. As a result, the definition of prognostic indicators enabling precise patient selection is mandatory for neoadjuvant or adjuvant therapies. The epithelial membrane protein (EMP2) was identified as one of the up-regulated genes by isoflavones. EMP2 overexpression suppressed foci formation, anchorage-independent growth in vitro, and tumorigenicity in severe combined immunodeficiency mice (all P < 0.05). In addition, a cross-talk between EMP2 and integrins αV and β3 was shown in the regulation of cell adhesion and migration. Higher EMP2 expression was associated with a better progression-free survival (P = 0.008) and cancer-related death (P < 0.001). EMP2 was identified as a tumor-suppressor gene in urinary tract urothelial carcinoma and may be an innovative co-targeting candidate for designing integrin-based cancer therapy.

We aimed to identify the effect of preoperative anemia on oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC) who had different levels of renal function.Between 2000 and 2013, we enrolled 370 patients who underwent radical nephroureterectomy for nonmetastatic UTUC. Preoperative anemia was defined as hemoglobin130g/l in men and120g/l in women based on the World Health Organization classification. Kaplan-Meier method was applied to estimate the effect anemia on survival, and hazard ratios (HR) of anemia and other clinicopathological parameters were evaluated by Cox regression model. The analyses were also performed in patients with different chronic kidney disease (CKD) stages.In all, 242 (65.4%) patients were anemic before surgery. Those with preoperative anemia had worse CKD stage (P0.001) and higher pathological tumor stage (P = 0.023). In univariate analysis, metastasis-free and cancer-specific survival rates were not significantly associated with preoperative anemia (HR = 1.51, 95% CI: 0.93-2.44, P = 0.093 and HR = 1.59, 95% CI: 0.93-2.72, PP = 0.094, respectively). However, in patients without stage 5 CKD, those with preoperative anemia had apparently inferior metastasis-free and cancer-specific survival than those without (HR = 1.88, 95% CI: 1.14-3.01, P = 0.014 and HR = 2.03, 95% CI: 1.16-3.56, P = 0.010, respectively). A multivariate Cox proportional hazards model indicated that preoperative anemia was an independent predictor for both metastasis-free (HR = 2.17, 95% CI: 1.21-3.90, P = 0.010) and cancer-specific survival (HR = 2.21, 95% CI: 1.15-4.21, P = 0.017).Among patients without stage 5 CKD, preoperative anemia was a significant prognostic factor to predict metastatic progression and cancer-specific death in UTUC following radical nephroureterectomy. It was important to be aware of patients׳ renal function while evaluating the effect of anemia on outcome of UTUC.

Aims HuR is an RNA-binding protein that post-transcriptionally modulates the expression of various target genes involved in carcinogenesis, such as CCNA2, which encodes cyclin A. The aim of this study was to evaluate the significance of HuR expression and subcellular localization in a large cohort of gastrointestinal stromal tumours (GISTs). Methods and results HuR immunostaining was assessable for nuclear and cytoplasmic expression in 341 cases on tissue microarrays of primary GISTs, of which 318, 296 and 193 cases were also characterized for Ki67 labelling, cyclin A immunoexpression, and KIT and PDGFRA receptor tyrosine kinase (RTK) genotypes, respectively. The results of HuR nuclear and cytoplasmic expression were correlated with disease-free survival (DFS) and clinicopathological, immunohistochemical and RTK genotypic variables. HuR cytoplasmic expression was present in 42% of primary GISTs, and was significantly related to epithelioid histology, larger tumour size, NIH risk category, and nuclear expression of Ki67 and cyclin A. Importantly, HuR cytoplasmic expression (P