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Background/purpose Several strategies have been reported for improving the integrity of transurethral resection of bladder tumor (TURBT). However, no standard has been established. Stratified TURBT (SR) is one of protocols for TURBT, wherein exophytic tumors are first resected and retrieved, and tumor bases are then resected. In this study, we aimed to evaluate the outcomes of SR in patients with nonmuscle invasive bladder cancer (NMIBC). Methods From January 2012 to December 2017, patients newly diagnosed as having NMIBC with a follow-up period of more than 2 years were enrolled and categorized into SR and conventional TURBT (CR) groups. Propensity score matching at a 2:1 ratio was performed. Outcomes were the detrusor muscle sampling rate, recurrence-free survival (RFS), and progression-free survival (PFS). Results In total, 205 patients were included in our study. The detrusor muscle sampling rate was higher in the SR group (P = 0.043). After propensity score matching, 162 patients were selected for outcome analysis, with 108 and 54 patients undergoing SR and CR, respectively. Compared with the CR group, the SR group showed a lower recurrence rate (P = 0.015) and better RFS in univariate (P = 0.010) and multivariate (P = 0.006) Cox proportional hazards regression. Progression rate and PFS were not significantly different between the two groups. Conclusion SR results in a higher detrusor muscle sampling rate and better disease outcomes. Our findings suggest that SR is a promising strategy for TURBT in patients with NMIBC.

Background: Aristolochic acids (AA) and arsenic are chemical carcinogens associated with urothelial carcinogenesis. Here we investigate the combined effects of AA and arsenic toward the risk of developing upper tract urothelial carcinoma (UTUC). Methods: Hospital-based (n = 89) and population-based (2,921 cases and 11,684 controls) Taiwanese UTUC cohorts were used to investigate the association between exposure to AA and/or arsenic and the risk of developing UTUC. In the hospital cohort, AA exposure was evaluated by measuring aristolactam-DNA adducts in the renal cortex and by identifying A>T TP53 mutations in tumors. In the population cohort, AA exposure was determined from prescription health insurance records. Arsenic levels were graded from 0 to 3 based on concentrations in well water and the presence of arseniasis-related diseases. Results: In the hospital cohort, 43, 26, and 20 patients resided in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Aristolactam-DNA adducts were present in >90% of these patients, indicating widespread AA exposure. A>T mutations in TP53 were detected in 28%, 44%, and 22% of patients residing in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Population studies revealed that individuals who consumed more AA-containing herbs had a higher risk of developing UTUC in both arseniasis-endemic and nonendemic areas. Logistic regression showed an additive effect of AA and arsenic exposure on the risk of developing UTUC. Conclusions: Exposure to both AA and arsenic acts additively to increase the UTUC risk in Taiwan. Impact: This is the first study to investigate the combined effect of AA and arsenic exposure on UTUC.

Recent advances in immune checkpoint inhibition, which augment T-cell immune responses, have highlighted the potential of exploiting one's immune system to combat cancer. However, only a relatively small number of non-small cell lung cancer (NSCLC) patients benefit from immune checkpoint blockade due to the immunosuppressive tumor microenvironment. Therefore, combination immunotherapies are now being developed to achieve maximal therapeutic benefits. In this study, we assessed whether a novel erlotinib derivative, TD-92, which possesses anti-tumor effects across several cancer cell lines, could enhance anti-PD-1 treatment. Our results demonstrated that the combined treatment of anti-PD-1 and TD-92 resulted in a potent anti-tumor response in a Lewis lung carcinoma cancer model, as evidenced by the reduced tumor growth and increased survival. Analysis of immune cell population counts revealed that TD-92 reduced the number of pro-tumorigenic CD11b+ F4/80+ tumor-associated macrophages, without significantly affecting the total numbers of other major immunocytes. Further experiments showed that TD-92 induced a marked decline in colony stimulating factor 1 receptor (CSF-1R) expression in macrophage cell lines. The results also suggested that c-Cbl-mediated proteasome degradation was involved in TD-92-mediated CSF-1R downregulation. Our data paves the way for the development of additional combination immunotherapies for NSCLC patients.

Purpose: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). Methods: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis

Background/Aim: Heterogeneous nuclear ribonucleoproteins (hnRNPs) contribute to multiple cellular functions including RNA splicing, stabilization, transcriptional and translational regulation, and signal transduction. However, the prognostic importance of genetic variants of hnRNP genes in clinical outcomes of prostate cancer remains to be elucidated. Patients and Methods: We studied the association of 78 germline single-nucleotide polymorphisms (SNPs) in 23 hnRNP genes with the overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). Results: PTBP1 rs10420407 was the most significant SNP (false discovery rate q=0.003) and carriers of the A allele exhibited poor OS, CSS, and PFS. Multivariate Cox analysis confirmed PTBP1 rs10420407 A allele was an independent negative prognostic factor for OS and PFS. Expression quantitative trait loci analysis showed that the rs10420407 A allele had a trend towards increased PTBP1 mRNA expression, and higher expression was correlated with prostate cancer aggressiveness and poor patient prognosis. Meta-analysis of 16 independent studies further indicated a tumorigenic effect of PTBP1, with a higher expression in prostate cancers than in adjacent normal tissues (p

Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD.A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients.Acr-dG levels were statistically correlated with CKD stages in UC patients (P0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P0.005).These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.

BACKGROUND Extended-field (EF) bone marrow-sparing (BMS) radiotherapy is attracting interest for cervical cancer patients with para-aortic lymphadenopathy. OBJECTIVE To compare dosimetric quality of volumetric-modulated arc therapy (VMAT) vs. helical tomotherapy (HT) during EF BMS radiotherapy. METHODS HT dose-volume histogram parameters including (1) coverage, homogeneity, and conformity of target volumes, (2) sparing of organs-at-risk, (3) monitor units, and (4) estimated treatment time were compared with those of VMAT in 20 cervical cancer patients who underwent EF BMS radiotherapy. The pelvic and para-aortic regions received 45-Gy dose (25 fractions), with simultaneous integrated boost of 55 Gy (25 fractions) for pelvic and para-aortic lymphadenopathy, followed by a parametrial boost of 9 Gy (5 fractions). RESULTS The HT-based and VMAT techniques achieved adequate and similar target volume coverage with good dose homogeneity and conformity, while sparing all organs-at-risk, including the rectum, bladder, bowel, bone marrow, femoral head, kidney, and spinal cord. The HT treatment plan had significantly higher monitor units (p

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

Background/aim This study aimed to identify the genes that cause biochemical recurrence (BCR) following radical prostatectomy (RP) in men with localized prostate cancer. Patients and methods A two-stage genetic association study of 19 single-nucleotide polymorphisms in 11 key cell cycle regulation genes was carried out. BCR-free survival after RP was evaluated in a discovery cohort of 458 patients with prostate cancer, and replication was investigated in another cohort of 185 patients. Results A consistent association was found between BCR and rs2290291 (discovery: p=0.008; replication: p=0.029). rs2290291 is located in the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), and was predicted to possess a regulatory function that affected YWHAZ expression. Furthermore, YWHAZ expression was frequently up-regulated in advanced tumours, and associated with poorer survival in patients with prostate cancer. Conclusion YWHAZ rs2290291 was found to be associated with BCR. YWHAZ may function as a putative oncogene during prostate cancer progression.

BackgroundProstate-specific antigen (PSA) is considered neither sensitive nor specific for prostate cancer (PCa). We aimed to compare total PSA (tPSA), percentage of free PSA (%fPSA), the PSA density (PSAD), Prostate Health Index (PHI), and the PHI density (PHID) to see which one could best predict clinically significant prostate cancer (csPCa): a potentially lethal disease.MethodsA total of 412 men with PSA of 2–20 ng/mL were prospectively included. Serum biomarkers for PCa was collected before transrectal ultrasound guided prostate biopsy. PHI was calculated by the formula: (p2PSA/fPSA) x √tPSA. PHID was calculated as PHI divided by prostate volume measured by transrectal ultrasound.ResultsOf the 412 men, 134 (32.5%) and 94(22.8%) were diagnosed with PCa and csPCa, respectively. We used the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA) to compare the performance of PSA related parameters, PHI and PHID in diagnosing csPCa. AUC for tPSA, %fPSA, %p2PSA, PSAD, PHI and PHID were 0.56、0.63、0.76、0.74、0.77 and 0.82 respectively for csPCa detection. In the univariate analysis, the prostate volume, tPSA, %fPSA, %p2PSA, PHI, PSAD, and PHID were all significantly associated with csPCa, and PHID was the most important predictor (OR 1.41, 95% CI 1.15–1.72). Besides, The AUC of PHID was significantly larger than PHI in csPCa diagnosis (p=0.004). At 90% sensitivity, PHID had the highest specificity (54.1%) for csPCa and could reduce the most unnecessary biopsies (43.7%) and miss the fewest csPCa (8.5%) when PHID ≥ 0.67. In addition to AUC, DCA re-confirmed the clinical benefit of PHID over all PSA-related parameters and PHI in csPCa diagnosis. The PHID cut-off value was positively correlated with the csPCa ratio in the PHID risk table, which is useful for evaluating csPCa risk in a clinical setting.ConclusionThe PHID is an excellent predictor of csPCa. The PHID risk table may be used in standard clinical practice to pre-select men at the highest risk of harboring csPCa.

PurposeThis study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy.MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches.ResultsAmong the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p ConclusionsMinimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further prospective studies are needed to validate our findings.

INTRODUCTION AND OBJECTIVE:To investigate the additional value of phi in predicting csPCa in Asian men with elevated PSA and MRI prostate performed.METHODS:This is a multicentre evaluation of prosp...

In this study, we investigated post-orchiopexy testicular growth of undescended testes (UDTs) at different primary locations and determined the risk factors for testicular atrophy (TA). We conducted a retrospective chart review of boys who had undergone orchiopexy for UDTs during January 2001–December 2013. Patient profile, age at operation, primary UDT location, and testicular volume were noted. TA was defined as ≥50% loss of volume after orchiopexy. The primary endpoints were testicular growth and TA after orchiopexy. The secondary endpoint was risk factors for TA. In total, 182 boys had undergone regular ultrasonography; the median follow-up period was 34 months. Among 230 UDTs, 18 (7.8%) atrophic testicles were identified within a median interval of 13 months after orchiopexy. TA rates were 3.3% (1/30), 6.9% (12/173), and 18.5% (5/27) in primary suprascrotal, canalicular, and above-inguinal UDTs, respectively. The survival probability of UDT was 91%, 92% and 100% when orchiopexy was performed in age ≤1 year, 1 2 years, respectively. Multivariate analysis revealed that inguinal and above-inguinal UDTs (hazard ratio [HR] 11.76, 95% confidence interval [CI] 1.55–89.33, p = 0.017) and genetic or endocrine disorders (HR 3.19, 95% CI 1.19–8.56, p = 0.021) were the risk factors for TA, but not age at operation, premature birth, and laterality. Thus, TA incidence was higher when patients had high primary testicular locations. Early orchiopexy before two years of age may be associated with higher TA risk, while most testicles have promising growth after orchiopexy.

The aberrant expression of cell adhesion molecules is a hallmark of epithelial‐to‐mesenchymal transition, resulting in the transformation of cancer cells to a more aggressive phenotype. This study investigated the association between genetic variants in cell adhesion pathways and the prognosis of patients with prostate cancer following radical prostatectomy (RP). A total of 18 haplotype‐tagging single‐nucleotide polymorphisms (SNPs) in eight cancer‐related adhesion molecules were genotyped in 458 prostate cancer patients, followed by the replication of the top SNPs in an additional set of 185 patients. Log‐rank test and multivariate Cox regression analysis adjusted for covariates were used to evaluate associations with the risk of biochemical recurrence (BCR) after RP. In the discovery set, four SNPs in CDH2 were marginally associated with BCR. Among these, CDH2 rs643555C > T was found to be associated with BCR in the replication set. Patients with rs643555TT genotype had a significantly shorter BCR‐free survival compared with those with CC/CT genotypes in the combined analysis (adjusted hazard ratio 1.78, 95% confidence interval 1.19‐2.67, P = 0.005). Additional analyses revealed that rs643555T was associated with higher expression of CDH2, and upregulated CDH2 was correlated with tumor aggressiveness and shortened BCR‐free survival. In conclusion, rs643555C > T affects CDH2 expression, and thus influences BCR in localized prostate cancer patients treated with RP. CDH2 rs643555 may be a promising biomarker to identify patients at high risk of poor prostate cancer prognosis.

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C &gt, T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p &lt, 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI), low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS), patients with age &gt, 60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.

OBJECTIVES: Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients. DESIGN: The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study. SETTING: Sixty-five ICUs across Europe. PATIENTS: For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay. MEASUREMENTS AND MAIN RESULTS: We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5-1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours; acute kidney injury stage 2 equals to serum creatinine × 2-2.9 times baseline; acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% (n = 100), acute kidney injury stage 2 equals to 1% (n = 14), and acute kidney injury stage 3 equals to 3% (n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1-4 d). Renal history (hazard ratio = 2.48; 95% CI, 1.39-4.43; p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52; 95% CI, 1.22-5.197; p = 0.012), hypernatremia (hazard ratio = 1.88; 95% CI, 1.31-2.71; p = 0.001), and osmotic therapy administration (hazard ratio = 2.08; 95% CI, 1.45-2.99; p < 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality. CONCLUSIONS: Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.

Aims The mitogen-activated protein kinase (MAPK) cascades integrate various upstream signals to regulate many cellular functions, including proliferation, differentiation, and survival. Dysregulation of these pathways has been implicated in the occurrence and progression of a variety of cancers. Main methods This study aimed to assess the association of 192 single nucleotide polymorphisms in 22 MAPK cascade genes with renal cell carcinoma (RCC) risk and survival in 312 patients and 318 controls. Key findings After multiple testing correction and multivariate analysis, the minor T allele of MAPK10 rs12648265 remained associated with a lower risk of RCC (adjusted odds ratio 0.64, 95% confidence interval 0.50–0.82, P = 0.000426) and metastasis (adjusted hazard ratio 0.50, 95% confidence interval 0.30–0.82, P = 0.006). Presence of the rs12648265 T allele demonstrated a trend towards being associated with increased MAPK10 expression, and meta-analysis of four RCC datasets indicated that high MAPK10 expression is associated with a favourable prognosis. Furthermore, activation of MAPK10 by the potent agonist anisomycin inhibited RCC cell growth in vitro, suggesting an involvement of MAPK10 in RCC progression. Significance In conclusion, MAPK10 may be a meaningful biomarker and a potential therapeutic target in RCC.

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded, the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p &lt, 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p &lt, 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121&ndash, 1.767, p = 0.003, cancer-specific survival: HR 1.562, 95% CI 1.169&ndash, 2.085, p = 0.003, disease-free survival: HR 1.363, 95% CI 1.095&ndash, 1.697, p = 0.006, bladder-recurrence-free survival: HR 1.411, 95% CI 1.141&ndash, 1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.

Objectives Augmented renal clearance might lead to subtherapeutic plasma levels of drugs with predominant renal clearance. Early identification of augmented renal clearance remains challenging for the ICU physician. We developed and validated our augmented renal clearance predictor, a clinical prediction model for augmented renal clearance on the next day during ICU stay, and made it available via an online calculator. We compared its predictive performance with that of two existing models for augmented renal clearance. Design Multicenter retrospective registry-based cohort study. Setting Three Belgian tertiary care academic hospitals. Patients Adult medical, surgical, and cardiac surgery ICU patients. Interventions None. Measurements and main results Development of the prediction model was based on clinical information available during ICU stay. Out of 33,258 ICU days, we found augmented renal clearance on 19.6% of all ICU days in the development cohort. We retained six clinical variables in our augmented renal clearance predictor: day from ICU admission, age, sex, serum creatinine, trauma, and cardiac surgery. We assessed performance by measuring discrimination, calibration, and net benefit. We externally validated the final model in a single-center population (n = 10,259 ICU days). External validation confirmed good performance with an area under the curve of 0.88 (95% CI 0.87-0.88) and a sensitivity and specificity of 84.1 (95% CI 82.5-85.7) and 76.3 (95% CI 75.4-77.2) at the default threshold probability of 0.2, respectively. Conclusions Augmented renal clearance on the next day can be predicted with good performance during ICU stay, using routinely collected clinical information that is readily available at bedside. Our augmented renal clearance predictor is available at www.arcpredictor.com.

Background: The role of salvage radiotherapy (RT) is established in prostate cancer patients undergoing radical prostatectomy (RP) with biochemical failure (BCF). Intensity modulated RT (IMRT) is adapted for post-RP treatment. This study aimed to investigate the prognostic factors and develop a nomogram to predict biochemical control in patients treated with exclusively salvage high-dose IMRT for post-RP BCF. Methods: One hundred and eleven patients underwent post-RP IMRT, and 92 patients were enrolled after excluding patients with adjuvant RT or lymph node metastasis on RP. Fifty-two percent of patients had androgen-deprivation therapy (ADT). Moreover, 20% and 34% had pathological T3a and T3b disease, respectively, and 70% had positive surgical margins. The median dose of IMRT was 70 Gy to the prostatic and seminal vesicle bed. Using multivariable Cox regression analysis, a nomogram model was generated to predict the probability of BCF after salvage IMRT. Results: The 5-year BCF-free survival (BFFS), metastasis-free survival (MFS), and overall survival (OS) after salvage IMRT were 56%, 89%, and 88%, respectively. Post-RP prostate-specific antigen (PSA) nadir > 0.1 ng/ml (p = 0.004), PSA > 0.5 ng/ml at salvage IMRT (p = 0.016), and Gleason score ≥ 8 (p = 0.013) were independent unfavorable prognostic factors for BFFS on multivariate analyses. The use of ADT, T3a/T3b disease, and positive surgical margins were not associated with BFFS. The predictions from the 3-factor nomogram (post-RP PSA nadir, pre-IMRT PSA, and Gleason score) appeared to be discriminative. The concordance index was 0.713, similar to 0.739 from the 7-factor nomogram with the addition of ADT, T3a/3b, positive margins, and IMRT dose ≥ 70 Gy. Conclusion: Salvage IMRT for post-RP BCF achieved a satisfactory outcome. The simplified 3-factor (post-RP PSA nadir, pre-IMRT PSA, and Gleason score) nomogram predicted biochemical control and demanded further validation.

The genes that influence prostate cancer progression remain largely unknown. Since the carboxylesterase gene family plays a crucial role in xenobiotic metabolism and lipid/cholesterol homeostasis, we hypothesize that genetic variants in carboxylesterase genes may influence clinical outcomes for prostate cancer patients. A total of 478 (36 genotyped and 442 imputed) single nucleotide polymorphisms (SNPs) in five genes of the carboxylesterase family were assessed in terms of their associations with biochemical recurrence (BCR)-free survival in 643 Taiwanese patients with prostate cancer who underwent radical prostatectomy. The strongest association signal was shown in CES1 (P = 9.64&times, 10-4 for genotyped SNP rs8192935 and P = 8.96 &times, 10-5 for imputed SNP rs8192950). After multiple test correction and adjustment for clinical covariates, CES1 rs8192935 (P = 9.67 &times, 10-4) and rs8192950 (P = 9.34 &times, 10-5) remained significant. These SNPs were correlated with CES1 expression levels, which in turn were associated with prostate cancer aggressiveness. Furthermore, our meta-analysis, including eight studies, indicated that a high CES1 expression predicted better outcomes among prostate cancer patients (hazard ratio 0.82, 95% confidence interval 0.70&ndash, 0.97, P = 0.02). In conclusion, our findings suggest that CES1 rs8192935 and rs8192950 are associated with BCR and that CES1 plays a tumor suppressive role in prostate cancer.

Background The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. Methods We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. Results One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. Conclusions Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. Trial registration ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.

INTRODUCTION AND OBJECTIVE:The negative initial prostate biopsy in men with suspected prostate cancer has an important role in oncological outcome. Repeat biopsy have been applied in many patients....

Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08–1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.

Background Hyperglycemia is associated with series of process leading to oncogenesis. Evidence has shown that diabetes mellitus (DM) seems to be associated with poor prognosis in patients with bladder cancer. However, evidence on the effect of glycemic control on the outcomes of bladder cancer is still limited. In the current study, we aimed to investigate the effect of DM and glycemic control on the prognosis of bladder cancer. Methods We conducted a retrospective chart review of a prospective database from January 2012 to December 2017. Patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included. They were classified into the DM and non-DM groups. Prognosis including recurrence rate, progression rate, recurrence-free survival (RFS), and progression-free survival was compared between the two groups. Subgroup analysis of the DM subgroup, in which patients were classified by HbA1C level, was conducted to investigate the effect of glycemic control. Results A total of 287 patients were included in our study, with 61 patients in the DM group and 226 patients in the non-DM group. No statistically significant difference was found in the prognosis between the DM and non-DM groups. Subgroup analysis revealed higher recurrence rate (P = 0.037) and worse RFS (log-rank P = 0.019) in patients with HbA1C ≥ 7. Conclusions DM is not a risk factor for recurrence and progression in patients with NMIBC. However, poor glycemic control is associated with poor prognosis in patients with both DM and NMIBC. Further prospective studies are needed to confirm current results.

Accumulating evidence suggests the roles of glutamate metabotropic receptors (GRMs) in cancer, in addition to synaptic signalling. The present study assessed the associations of genetic variants in eight GRM genes with regard to risk and overall survival (OS) in 780 renal cell carcinoma (RCC) patients and controls. After adjustment for known risk factors, GRM5 rs7102764 T was associated with an increased risk of RCC (P = 0.006). Additional analysis has provided evidence that rs7102764 T was correlated with a higher expression of GRM5, which is consistently found to be upregulated in tumours, compared to normal tissues. Furthermore, the GRM3 rs701332 C, GRM4 rs2499707 T, and GRM4 rs4713742 T alleles were significantly associated with a poorer OS (P ≤ 0.030). The three loci were also observed to have strong cumulative effects on OS. Additional analysis has revealed a significant genotype‐expression correlation of rs2499707 T with increased GRM4 expression, which in turn leads to poorer OS in patients with RCC. GRMs might be involved in RCC development and progression, and genetic variants in GRMs might be promising biomarkers.

Aim Palbociclib is an oral cyclin-dependent kinase 4/6 inhibitor, which is efficacious in treating breast cancer. Currently, there are numerous active clinical trials testing palbociclib alone or in combination with other medications for treating various types of malignancies. Here, we evaluated the anti-cancer effect of palbociclib in combination with radiation therapy (RT) for treating human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) and addressed the molecular mechanism behind the combination therapy. Methods Immunofluorescence staining of γH2AX or 53BP1 was used to determine the effect of palbociclib on double-strand break (DSB) repair. Clonogenic assays, sphere formation and cell death ELISA were performed to study the sensitising effect of palbociclib on radiation-induced cytotoxicity. Signal alteration in DSB repair pathways was examined by Western blot analysis. Finally, we evaluated the in vivo anti-cancer activity and the associated molecular events of the combination therapy in a preclinical HCC xenograft model. Results Palbociclib affected the kinetics of DNA repair and enhanced the radiation sensitivity of HCC and CCA cells. Importantly, we found that palbociclib inhibits ataxia telangiectasia–mutated (ATM) kinase, the key upstream kinase responding to RT-induced DSBs. Furthermore, we showed that the inhibitory effect of palbociclib on RT-induced ATM kinase activation is mediated by protein phosphatase 5 (PP5). Both in vitro and in vivo investigations revealed that the inhibition of the PP5-ATM axis by palbociclib after DNA damage is responsible for the synergism between palbociclib and RT. Conclusion Our findings provide a novel combination strategy against liver cancer cells. Clinical trials using palbociclib as an adjuvant in RT are warranted.

Our recent study found that high urinary total arsenic levels were associated with renal cell carcinoma (RCC). Recent studies demonstrated that low circulating adiponectin was related to RCC. The aim of the present study was to explore the relationship between adiponectin gene (ADIPOQ) polymorphisms and RCC and investigate whether individuals with an ADIPOQ risk genotype, obesity, and high urinary total arsenic levels have a modified odds ratio (OR) of RCC. A total of 389 RCC patients and 389 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Image-guided biopsy or surgical resection of renal tumors was performed to pathologically verify RCC. Genomic DNA was used to examine the genotypes of the ADIPOQ rs182052, ADIPOQ rs2241766, ADIPOQ rs1501299, and ADIPOQ rs1063539 SNPs by PCR-RFLP. HPLC-HG-AAS was used to measure the concentrations of urinary arsenic species. Participants with the ADIPOQ rs182052 G/A+A/A genotype had a significantly higher OR of RCC compared with those with the ADIPOQ rs182052 G/G genotype. The OR (95% confidence interval [CI]) was 1.70 (1.23–2.36). The OR of RCC for the combined effect of high urinary total arsenic levels and obesity, which was dose-dependent, in individuals with the ADIPOQ rs182052 G/A+A/A genotype was 9.33 (3.85–22.62). The present study found significant combined effects of obesity and the ADIPOQ rs182052 G/A+A/A genotype on the arsenic-related risk of RCC in a population with low arsenic exposure. Arsenic exposure, obesity, and the ADIPOQ rs182052 polymorphism could be predictors of a higher OR of RCC.

Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiation therapy (RT)-mediated anticancer effects has not yet been explored. We investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assays, we found that RT-induced proliferative inhibition was critically associated with SET expression. We next tested a novel SET antagonist, N4-(3-ethynylphenyl)-6,7-dimethoxy-N2-(4-phenoxyphenyl) quinazoline-2,4-diamine (EMQA), in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared with mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore protein phosphatase 2A-mediated phospho-Akt (p-AKT) downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach.

Single nucleotide polymorphisms (SNPs) within the regulatory elements of a gene can alter gene expression, making these SNPs of prime importance for candidate gene association studies. We aimed to determine whether such regulatory variants are associated with clinical outcomes in three cohorts of patients with prostate cancer. We used RegulomeDB to identify potential regulatory variants based on in silico predictions and reviewed genome‐wide experimental findings. Overall, 131 putative regulatory SNPs with the highest confidence score on predicted functionality were investigated in two independent localized prostate cancer cohorts totalling 458 patients who underwent radical prostatectomy. The statistically significant SNPs identified in these two cohorts were then tested in an additional cohort of 504 patients with advanced prostate cancer. We identified one regulatory SNPs, rs1646724, that are consistently associated with increased risk of recurrence in localized disease (P = .003) and mortality in patients with advanced prostate cancer (P = .032) after adjusting for known clinicopathological factors. Further investigation revealed that rs1646724 may affect expression of SLC35B4, which encodes a glycosyltransferase, and that down‐regulation of SLC35B4 by transfecting short hairpin RNA in DU145 human prostate cancer cell suppressed proliferation, migration and invasion. Furthermore, we found increased SLC35B4 expression correlated with more aggressive forms of prostate cancer and poor patient prognosis. Our study provides robust evidence that regulatory genetic variants can affect clinical outcomes.

// Herng-Ching Lin 1, 2 , Li-Ting Kao 2, 3, * , Shiu-Dong Chung 4 , Chung-Chien Huang 1, * , Ben-Chang Shia 5, * and Chao-Yuan Huang 6, 7, * 1 School of Health Care Administration, Taipei Medical University, Taipei, Taiwan 2 Sleep Research Center, Taipei Medical University Hospital, Taipei, Taiwan 3 Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan 4 Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, Banciao, New Taipei City, Taiwan 5 Big Data Research Center, Taipei Medical University, Taipei, Taiwan 6 Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan 7 School of Public Health, Taipei Medical University Hospital, Taipei, Taiwan * These authors contributions equaly to this work Correspondence to: Chao-Yuan Huang, email: cyh540909@gmail.com Keywords: Alzheimer’s disease; prostate cancer; epidemiology Received: July 25, 2017 Accepted: January 04, 2018 Published: January 10, 2018 ABSTRACT Alzheimer’s disease and cancer are increasingly prevalent with advancing age. However, the association between Alzheimer’s disease and prostate cancer remains unclear. The aim of this study was to examine the relationship between prior Alzheimer’s disease and subsequent prostate cancer using a population-based dataset in Taiwan. Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2005. This case-control study included 2101 prostate cancer patients as cases and 6303 matched controls. We used conditional logistic regression analyses to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for Alzheimer’s disease between prostate cancer patients and controls. We found that of the 8404 sampled patients, 128 (1.5%) had been diagnosed with Alzheimer’s disease prior to the index date. A Chi-squared test showed that there was a significant difference in the prevalences of prior Alzheimer’s disease between prostate cancer patients and controls (2.1% vs. 1.3%, p < 0.001). The conditional logistic regression analysis showed that the OR of prior Alzheimer’s disease for prostate cancer patients was 1.53 (95% CI: 1.06~2.21) compared to controls. Furthermore, the OR of prior Alzheimer’s disease for prostate cancer patients was 1.52 (95% CI: 1.04~2.22) compared to controls after adjusting for hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, prostatitis, gonorrhea or chlamydia infection, testitis or epididymitis, and alcohol abuse/alcohol dependency syndrome. This study revealed an association between prior Alzheimer’s disease and prostate cancer. We suggest that clinicians be alert to the increased risk of prostate cancer when caring for elderly individuals with Alzheimer’s disease.

AIMS Mutations in FGFR3 and the promoter region of the telomerase reverse transcriptase (TERT) gene have been found frequently in urothelial carcinoma of the urinary bladder. However, related data for papillary urothelial neoplasm of low malignant potential (PUNLMP) are limited. In this study, we investigated the mutation status of the TERT promoter, FGFR3 and HRAS in low-grade papillary urothelial neoplasms and evaluated their prognostic significance. METHODS AND RESULTS The cases included in this study comprised 21 inverted papillomas, 30 PUNLMPs and 34 low-grade non-invasive papillary urothelial carcinomas (NIPUCs). TERT promoter mutations were observed in 10 (33%) PUNLMPs and 17 (50%) low-grade NIPUCs, but not in any inverted papilloma. FGFR3 mutations were observed more frequently in PUNLMP and low-grade NIPUC than in inverted papillomas (P = 0.009), whereas the opposite trend was noted for HRAS mutations (P

Even though the relationship between antiarrhythmic drug usage and subsequent prostate cancer (PCa) risk has recently been highlighted, relevant findings in the previous literature are still inconsistent. In addition, very few studies have attempted to investigate the association between sodium channel blockers or potassium channel blockers for arrhythmia and the subsequent PCa risk. Therefore, this cohort study aimed to find the relationship between antiarrhythmic drug usage and the subsequent PCa risk using a population-based dataset. The data used in this study were derived from the Longitudinal Health Insurance Database 2005, Taiwan, China. We respectively identified 9988 sodium channel blocker users, 3663 potassium channel blocker users, 65 966 beta-blocker users, 23 366 calcium channel blockers users, and 7031 digoxin users as the study cohorts. The matched comparison cohorts (one comparison subject for each antiarrhythmic drug user) were selected from the same dataset. Each patient was tracked for a 5-year period to define those who were subsequently diagnosed with PCa. After adjusting for sociodemographic characteristics, comorbidities, and age, Cox proportional hazard regressions found that the hazard ratio (HR) of subsequent PCa for sodium channel blocker users was 1.12 (95% confidence interval [CI]: 0.84–1.50), for potassium channel blocker users was 0.89 (95% CI: 0.59–1.34), for beta-blocker users was 1.08 (95% CI: 0.96–1.22), for calcium channel blocker users was 1.14 (95% CI: 0.95–1.36), and for digoxin users was 0.89 (95% CI: 0.67–1.18), compared to their matched nonusers. We concluded that there were no statistical associations between different types of antiarrhythmic drug usage and subsequent PCa risk.

Cigarette smoking and exposure to environmental tobacco smoke are well-known risk factors for urothelial carcinoma (UC). We conducted a hospital-based case-control study involving 287 UC cases and 574 cancer-free controls to investigate the joint effects of cigarette smoking and polymorphisms of inflammatory genes on UC risk. Tumor necrosis factor alpha (TNF-α) -308 G/A and interleukin-8 (IL-8) -251 T/A polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism method. People who had ever smoked and those who were exposed to environmental tobacco smoke had significantly increased UC odds ratios (ORs) of 1.65 and 1.68, respectively. Participants who had smoked more than 18 pack-years had a significantly increased UC OR of 2.64. People who had ever smoked and who carried the A/A genotype of the TNF-α -308 G/A polymorphism had a significantly higher UC OR (10.25) compared to people who had never smoked and who carried the G/G or G/A genotype. In addition, people who had ever smoked and who carried the IL-8 -251 T/T genotype had a significantly increased UC OR (3.08) compared to people who had never smoked and who carried the T/A or A/A genotype. In a combined analysis of three major risk factors (cumulative cigarette smoking, the TNF-α -308 A/A genotype, and the IL-8 -251 T/T genotype), subjects with any one, any two, and all three risk factors experienced significantly increased UC ORs of 1.55, 2.89, and 3.77, respectively, compared to individuals with none of the risk factors. Conclusions. Our results indicate that the combined effects of cumulative cigarette exposure and the TNF-α -308 A/A genotype and/or the IL-8 -251 T/T genotype on UC OR showed a significant dose-response relationship.

Purpose: The purpose of this study is to investigate the clinical oncological outcomes and prognostic factors of high-volume disease (HVD) in the Asian population with metastatic hormone-sensitive prostate cancer. Methods: We retrospectively analyzed 503 patients with newly diagnosed metastatic prostate cancer. Patients were classified as HVD if visceral metastases were present and/or ≥4 bone lesions with ≥1 lesion beyond the vertebral bodies and pelvis. Overall survival (OS) and cancer-specific survival were investigated based on the disease burden. The Cox proportional hazards regression model was used to evaluate the prognostic factors. Results: About 50.7% patients were classified as low-volume disease (LVD) and 49.3% were HVD at diagnosis. The medians of OS and cancer-specific survival were 64 and 116 months, respectively, for patients with LVD and 26 and 46 months, respectively, for men with HVD (both P < 0.001). Among patients with HVD, 76.6% had both high-volume bone disease (HBD) (≥4 bone metastases) and appendicular bone involvement. There was no significant difference in both OS and cancer-specific survival between patients with visceral metastases and those with HBD combined with appendicular bone involvement. In the multivariable analysis, presence of Gleason score ≥8, HBD, or HVD may predict poorer OS and cancer-specific survival outcomes (all P < 0.05). Conclusions: Asian patients with high-volume metastatic prostate cancer had a larger proportion of HBD with appendicular bone involvement, who had a comparably poor prognosis to those with visceral metastases. Patients with HBD or HVD had reduced survival outcomes.

Background/purpose This study evaluated the long-term outcomes of nephrectomy and inferior vena cava (IVC) thrombectomy in patients with advanced renal cell carcinoma (RCC). Methods From January 1996 to December 2013, we retrospectively collected the clinical data of 31 patients with pathologically confirmed RCC and IVC tumor thrombus. All patients received nephrectomy and IVC thrombectomy. We examined the clinical outcomes, including cancer-specific survival, progression-free survival, and postoperative complications, during a 90-day period. The associated prognostic factors were also analyzed. This study is registered with the National Taiwan University Hospital Research Ethics Committee (number 201305059RINC). Results The median follow-up period was 24 months. Of 20 patients with nonmetastatic disease, 15 developed metastases during the study period. The overall 5-year cancer-specific survival rate was 30.8% in the nonmetastatic group versus 12.5% in the metastatic group. The level of IVC thrombus (levels I–II versus levels III–IV) was not significantly associated with the 5-year cancer-specific survival (p = 0.43). The Fuhrman grade and sarcomatoid type were statistically significant predictors of cancer-specific survival [Fuhrman grades III–IV versus grades I–II: hazard ratio (HR) = 0.11, p = 0.04; sarcomatoid type: HR = 0.136, p = 0.001]. Fuhrman grade, capsular invasion, and positive surgical margins were associated with 1-year progression-free survival (Fuhrman grades III–IV versus grades I–II: HR = 0.08, p = 0.04; capsular invasion: HR = 0.15, p = 0.04; positive surgical margins: HR = 0.16, p = 0.05). The most common perioperative complication was massive blood loss. The most common recurrence sites were bones, liver, and lungs. Conclusion The pathologic Fuhrman grade, sarcomatoid type, positive surgical margins, and capsular invasion were significant predictors of oncological outcomes in patients with advanced RCC and IVC thrombus.

Objective: Atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two pathological findings occasionally noted in prostate biopsies. Previous Western studies reported that they were associated with prostate cancer. However, none Taiwanese series report the subsequent cancer detection in ASAP and HGPIN patients. This study aimed to examine the results of repeated biopsies in the patients with ASAP and HGPIN. Materials and Methods: A total of 220 consecutive patients with ASAP and/or HGPIN at our institute between January 1990 and December 2010 were enrolled. Patient demographics and clinical information were extracted from the electronic database of our institute. Prostate biopsies were performed through transrectal ultrasound guidance. The patients who had concurrent prostate cancer (n = 51) and no repeated prostate biopsies (n = 103) were excluded from the study. Patients with biopsy pathologies reporting low-grade prostatic intraepithelial neoplasia (n = 2) were also excluded. The remaining 64 patients were available for the final analysis. Results: Nearly, 38, 24, and 2 patients were initially diagnosed as ASAP, HGPIN, and ASAP along with HGPIN, respectively. After 10 years of follow-up, 36.8% patients in ASAP group developed prostate cancer, while 16.7% in HGPIN group and 100% in ASAP + HGPIN group. Median time to developing prostate cancer were 20 months in ASAP group, 31 months in HGPIN group, and 48 months in ASAP + HGPIN group. There was no significant difference of prostate cancer development between ASAP and HGPIN group (P = 0.291). Only older age, classified by 65 years, was significantly associated with a higher detection rate of prostate cancer. Conclusion: Patients with the initial diagnosis of ASAP or PIN has a high risk of developing prostate cancer. Therefore, those patients should be well announced and followed regularly.

Although shock wave lithotripsy is minimally invasive, earlier studies argued that it may increase patients’ subsequent risk of hypertension and diabetes mellitus. This study evaluated the association between shock wave lithotripsy and new-onset hypertension or diabetes mellitus. The Taiwanese National Health Insurance Research Database was used to identify 20 219 patients aged 18 to 65 years who underwent the first stone surgical treatment (shock wave lithotripsy or ureterorenoscopic lithotripsy) between January 1999 and December 2011. A Cox proportional model was applied to evaluate associations. Time-varying Cox models were applied to evaluate the association between the number of shock wave lithotripsy sessions and the incidence of hypertension or diabetes mellitus. After a median follow-up of 74.9 and 82.6 months, 2028 and 688 patients developed hypertension in the shock wave lithotripsy and ureterorenoscopic lithotripsy groups, respectively. Patients who underwent shock wave lithotripsy had a higher probability of developing hypertension than patients who underwent ureterorenoscopic lithotripsy, with a hazard ratio of 1.20 (95% confidence interval, 1.10–1.31) after adjusting for covariates. The risk increased as the number of shock wave lithotripsy sessions increased. However, the diabetes mellitus risk was similar in the shock wave lithotripsy and ureterorenoscopic lithotripsy groups. Furthermore, the hazard ratio did not increase as the number of shock wave lithotripsy sessions increased. Shock wave lithotripsy consistently increased the incidence of hypertension on long-term follow-up. Therefore, alternatives to urolithiasis treatment (eg, endoscopic surgery or medical expulsion therapy) could avoid the hypertension risk. Furthermore, avoiding multiple sessions of shock wave lithotripsy could also evade the hypertension risk.

// Victor C. Lin 1, 2 , Shu-Pin Huang 3, 4, 5 , Huei-Ju Ting 6 , Wen-Lung Ma 7, 8 , Chia-Cheng Yu 9, 10, 11 , Chao-Yuan Huang 12, 13 , Hsin-Ling Yin 14, 15 , Tsung-Yi Huang 3 , Cheng-Hsueh Lee 3, 5 , Ta-Yuan Chang 16 , Te-Ling Lu 17 and Bo-Ying Bao 8, 17, 18 1 Department of Urology, E-Da Hospital, Kaohsiung 824, Taiwan 2 School of Medicine for International Students, I-Shou University, Kaohsiung 840, Taiwan 3 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan 5 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan 6 Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan 7 Graduate Institution of Clinical Medical Science, and Graduate Institution of Cancer Biology, China Medical University, Taichung 404, Taiwan 8 Sex Hormone Research Center, China Medical University Hospital, Taichung 404, Taiwan 9 Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan 10 Department of Urology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan 11 Department of Pharmacy, Tajen University, Pingtung 907, Taiwan 12 Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan 13 Department of Urology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan 14 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan 15 Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan 16 Department of Occupational Safety and Health, China Medical University, Taichung 404, Taiwan 17 Department of Pharmacy, China Medical University, Taichung 404, Taiwan 18 Department of Nursing, Asia University, Taichung 413, Taiwan Correspondence to: Bo-Ying Bao, email: bao@mail.cmu.edu.tw Keywords: progression, prostate cancer, single nucleotide polymorphisms, vitamin D receptor, susceptibility genes Received: April 04, 2017 Accepted: May 15, 2017 Published: May 26, 2017 ABSTRACT Vitamin D is an important modulator of cellular proliferation through the vitamin D receptor (VDR) that binds to DNA in the regulatory sequences of target genes. We hypothesized that single nucleotide polymorphisms (SNPs) in VDR-binding sites might affect target gene expression and influence the progression of prostate cancer. Using a genome-wide prediction database, 62 SNPs in VDR-binding sites were selected for genotyping in 515 prostate cancer patients and the findings were replicated in an independent cohort of 411 patients. Prognostic significance on prostate cancer progression was assessed by Kaplan-Meier analysis and the Cox regression model. According to multivariate analyses adjusted for known predictors, HFE rs9393682 was found to be associated with disease progression for localized prostate cancer, and TUSC3 rs1378033 was associated with progression for advanced prostate cancer in both cohorts. Vitamin D treatment inhibited HFE mRNA expression, and down-regulation of HFE by transfecting small interfering RNA suppressed PC-3 human prostate cancer cell proliferation and wound healing ability. In contrast, vitamin D treatment induced TUSC3 expression, and silencing TUSC3 promoted prostate cancer cell growth and migration. Further analysis of an independent microarray dataset confirmed that low TUSC3 expression correlated with poor patient prognosis. Our results warrant further studies using larger cohorts. This study identifies common variants in VDR-binding sites as prognostic markers of prostate cancer progression and HFE and TUSC3 as plausible susceptibility genes.

To date, the relationship between antimuscarinics for overactive bladder (OAB) syndrome and depressive disorder still remains unclear. Therefore, this retrospective cohort study examined the association between antimuscarinic use and the subsequent risk of depressive disorder using a population-based data set. This study used data from the Taiwan Longitudinal Health Insurance Database 2005. We selected 1952 OAB women who received antimuscarinics as the study cohort and 9760 OAB women who did not receive antimuscarinics as the comparison cohort. Each subject was tracked for 3 years from her index date to determine all those who were subsequently diagnosed with depressive disorder. Results indicated that the adjusted hazard ratio (HR) for depressive disorder in OAB women who received antimuscarinics was 1.38 (95% confidence interval [CI], 1.15-1.64) compared with those OAB women who did not receive antimuscarinics. In addition, the adjusted HRs for subsequent depressive disorder for OAB women aged 18-39, 40-59, and ≥60 years who received antimuscarinics were 1.83 (95%CI, 1.27-2.64), 1.36 (95%CI, 1.03-1.81), and 1.16 (95%CI, 0.86-1.56), respectively, compared with those OAB women who did not receive antimuscarinics. We concluded that women with OAB who received antimuscarinics had a significantly higher risk of subsequent depressive disorder compared with those OAB women who did not receive antimuscarinics. Accordingly, clinicians should be alert to the relationship between antimuscarinics usage and depressive disorder in OAB women and provide appropriate instructions for these patients.

Background: Cancer stem cells (CSCs) are involved in tumor progression and drug resistance. We hypothesized that variants in CSC marker genes influence treatment outcomes in prostate cancer. Methods: Ten potentially functional single nucleotide polymorphisms (SNPs) in seven prostate CSC marker genes, TACSTD2, PROM1, ITGA2, POU5F1, EZH2, PSCA, and CD44, were selected for analysis of their association with disease recurrence by Kaplan-Meier analysis and Cox regression in a cohort of 320 patients with localized prostate cancer receiving radical prostatectomy. Results: We identified one independent SNP, rs2394882, in POU5F1 that was associated with prostate cancer recurrence (hazard ratio 0.32, 95% confidence interval 0.14-0.71, P = 0.005) after adjustment for known clinical predictors. Further in silico functional analyses revealed that rs2394882 affects POU5F1 expression, which in turn is significantly correlated with prostate cancer aggressiveness and patient prognosis. Conclusion: Our results suggest that rs2394882 is prognostically relevant in prostate cancer, possibly by modulating the expression of the CSC gene POU5F1.

Cluster of differentiation (CD) antigens are cell surface markers used to differentiate haematopoietic cell types. These antigens are present in various malignancies and are reportedly linked to patient prognosis, however, they have not been implemented as prostate cancer progression markers. Here, we aimed to assess the impact of genetic variation in haematopoietic cell CD markers on clinical outcomes in patients with prostate cancer. An association study of 458 patients with prostate cancer was conducted to identify single-nucleotide polymorphisms in 11 candidate CD marker genes associated with biochemical recurrence (BCR) after radical prostatectomy. Identified predictors were further evaluated in an additional cohort of 185 patients. Joint population analyses showed that CD1B rs3181082 is associated with BCR (adjusted hazard ratio 1.42, 95% confidence interval 1.09&ndash, 1.85, p = 0.010). In addition, rs3181082 overlapped with predicted transcriptional regulatory elements and affected CD1B expression. Furthermore, low CD1B expression correlated with poorer BCR-free survival. Our results indicated that CD1B rs3181082 confers prostate cancer progression and may help improve clinical prognostic stratification.

Anoctamins were originally identified as a family of calcium‐activated chloride channels, but recently their roles in the development of different types of malignancies were suggested. Here, we evaluated the associations between 211 common single‐nucleotide polymorphisms in 10 anoctamin genes with biochemical recurrence (BCR) after radical prostatectomy (RP) for localized prostate cancer. Four SNPs (ANO4 rs585335, AN O5 rs4622263, ANO7 rs62187431, and ANO10 rs118005571) remained significantly associated with BCR after multiple test correction (P, Our genetic association study identified that ANO5 rs4622263 was associated with recurrence‐free survival in patients with prostate cancer following radical prostatectomy. Additional analyses also provided evidence that rs4622263 affects ANO5 expression, which in turn is correlated with tumor aggressiveness and patient prognosis.

This study aimed to investigate the risks of thromboembolic vascular disease following androgen deprivation therapy (ADT) administered to prostate cancer (PCa) patients. A total of 24,464 men with newly diagnosed PCa during 2000–2008 were recruited through a longitudinal health insurance database in Taiwan. All PCa patients were stratified into two: ADT and non-ADT groups. Patients with ADT treatment were grouped into three: surgical castration, chemical castration, and anti-androgen alone. The risks of pulmonary embolism (PE), peripheral arterial occlusion disease (PAOD), and deep vein thrombosis (DVT) were assessed in multiple Cox proportional-hazards regression with time-dependent covariates. During the 12-year follow-up period, incidence rates per 1000 person-years in ADT and non-ADT groups were 2.87 and 1.62 for DVT, 1.00 and 0.52 for PE, and 1.03 and 0.70 for PAOD, respectively. The DVT and PE risks were significantly increased in patients receiving combined androgen blockade (CAB) compared with the counterpart ADT non-recipients. After adjusting for potential risk factors, PCa patients receiving CAB had the highest PE risk (HR = 3.11), followed by DVT risk (HR = 2.53). The DVT risk remained elevated throughout the entire duration of chemical castration. However, high PE risk was observed in patients with ≤720-day treatment duration. No association was found between ADT and PAOD risks. Overall, the risks of PE and DVT were considerably heightened in Asian men subjected to CAB for PCa, whereas PAOD risk was unrelated to such treatments.

Background/Purpose: The inflammatory milieu has been firmly established to affect cancer progression. However, the connection between natural killer (NK) cells and prostate cancer (PCa) has not been elucidated. Methods: Prospective data on NK cell activity (NKA) and NK cell subset distribution patterns were evaluated from 51 patients treated with robot-assisted laparoscopic radical prostatectomy. Whole-blood samples were collected from patients preoperatively and 4–6 weeks postoperatively. The samples were subjected to NKA tests, NK cell number counts, determination of the NKG2D (activating receptor of NK cells), NKG2A (inhibiting receptor), and other surface markers. All the analyses were compared to the clinicopathological characteristics of patients. NKA was estimated by measuring interferon-γ (IFN-γ) levels after stimulation of the peripheral blood with PROMOCA™, which specifically stimulates the release of IFN-γ from NK cells. Results: NKA was lower in patients with PCa than in healthy participants (484.66 vs. 1550 pg/mL). A paired comparison revealed significantly higher NKA postoperatively than preoperatively (1054 vs. 484.66 pg/mL; p = 0.011). Patients with negative surgical margins exhibited significantly higher postoperative NKA and NKA ratio (postoperative NKA/preoperative NKA) than those with positive margins (557 vs. 1921 pg/mL, p

Background To determine the association between circadian pathway genetic variants and the risk of prostate cancer progression. Methods We systematically evaluated 79 germline variants in nine circadian pathway genes in a cohort of 458 patients with localized prostate cancer as the discovery phase. We then replicated the significant findings in another cohort of 324 men with more advanced disease. The association of each variant with prostate cancer progression was evaluated by a log-rank test and Cox regression. Results A single nucleotide polymorphism of the neuronal PAS domain protein 2 (NPAS2) gene (rs6542993 A>T) was found to be associated with a significantly higher risk of disease progression in both localized (P = 0.001) and advanced (P = 0.039) prostate cancer cases. In silico analysis revealed decreased expression levels of NPAS2 in carriers of the T allele of rs6542993 compared with those carrying the A allele. Consistently, downregulation of NPAS2 expression was associated with more aggressive prostate cancer and poor progression-free survival (log-rank P = 0.002). Conclusions The NPAS2 rs6542993 polymorphism may be a promising biomarker, and may shed light on the pathways that govern prostate cancer progression. Electronic supplementary material The online version of this article (10.1186/s12935-019-0811-4) contains supplementary material, which is available to authorized users.

INTRODUCTION AND OBJECTIVES:Prostate health index (PHI) is a promising biomarker in the prediction of aggressive prostate cancer. Since prostate volume has been regarded as an important factor cont...

INTRODUCTION AND OBJECTIVES:In the literature, the percentage of bacterial etiology in pediatric acute epididymitis is around 16-31%. However, more than 80% of patients received antibiotic treatmen...

INTRODUCTION AND OBJECTIVES:The aim of this study was to investigate the relationship between the use of androgen deprivation therapy (ADT) and the subsequent risk of cognitive decline in Asian men...