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Purpose: To compare perioperative outcomes according to surgical methods among bladder cancer patients who underwent radical cystectomy (RC) with neobladder urinary diversion.Materials and Methods: Between June 2007 and January 2020, 89 bladder cancer patients who received RC with neobladder urinary diversion were enrolled in this study. Patients were stratified into surgical methods – (1) open RC with neobladder (ONB) reconstruction, (2) robotassisted RC (RARC) with extracorporeal neobladder (ECNB) reconstruction, and (3) RARC with intracorporeal neobladder (ICNB) reconstruction. Perioperative outcomes were compared among the 3 groups, with major complications defined according to Clavien-Dindo grades III–V within 90 days. Logistic regression analysis was performed to identify significant factors for postoperative complications.Results: Of 89 patients, 28 (31%) had ONB, 31 (35%) had ECNB, and 30 (34%) had ICNB. The median operative time was 471 minutes, and the ICNB group (424.5 minutes) was significantly less than ONB (444.5 minutes) and ECNB groups (542.9 minutes) (p=0.001). Transfusion rate was also significantly less in the ICNB group (13%) (p=0.001). Complications were recorded in 67 patients (75%) and major complications in 22 of all patients (25%). The major complication rate was significantly less in ICNB (13.4%) than in ONB (25%) and ECNB (35%) (p=0.003). Multivariate analysis showed surgical methods (ICNB) (odds ratio [OR], 0.709; p=0.003) and age (OR, 1.150; p=0.001) were significant factors related to occurrence of major postoperative complications.Conclusions: RARC with ICNB reduces postoperative complications compared to ONB and ECNB.

Background There are limited data concerning patients treated with sequential bilateral kidney surgery. Current guidelines still lack an optimal surgical sequencing approach. We evaluated renal functional outcomes after sequential partial nephrectomy (PN) and radical nephrectomy (RN) in patients with bilateral renal cell carcinoma (RCC). Methods A propensity score matched cohort of 267 patients (synchronous bilateral RCCs, N = 44 [88 lesions]; metachronous bilateral, N = 45 [90 lesions]; unilateral, N = 178) from two tertiary institutions were retrospectively analyzed. Synchronous bilateral RCCs were defined as diagnosis concomitantly or within 3 months of former tumor. Renal functional outcomes were defined as estimated glomerular filtration rate (eGFR) changes and de novo chronic kidney disease (CKD, stage ≥3) after surgery. Renal functional outcomes and clinical factors predicting de novo CKD were assessed using descriptive statistics and Cox regression analysis. Results In subgroup of bilateral RCCs, patients underwent sequential PN (N = 48), PN followed by RN (N = 8), or RN followed by PN (N = 25). Final postoperative estimated glomerular filtration rates (eGFRs) were 79.4, 41.4, and 61.2 ml/minute/1.73 m2, respectively (p = 0.003). There were significant differences in eGFR decline from baseline and de novo chronic kidney disease (CKD stage ≥ III) among groups, with PN followed by RN group showing the worst functional outcomes (all p p = 0.016). On multivariate analysis, hypertension (p = 0.010) and surgery sequence (PN followed by RN, p Conclusions The surgery sequence should be prudently determined in bilateral renal tumors. PN followed by RN showed a negative impact on renal functional preservation. Nephron-sparing surgery should be considered for all amenable bilateral RCCs.

Background Ureaplasma parvum (UP) is commonly isolated in the genitor-urinary tract and may cause various clinical features, including microscopic hematuria (MH). Some UP serovars are more commonly related with specific urogenital disease, but the evidences have been conflicting. This study primarily aimed to research the possible associations between specific UP serotypes and genito-urinary pathogenicity in female patients showing MH with/without chronic micturition urethral pain (CMP). Methods This study retrospectively reviewed 276 female patients having MH with/without CMP, who visited health screening center or female infertility clinic. All patients underwent multiplex polymerase chain reaction (PCR) tests with vaginal and urine samples to evaluate the infection rate and serotypes of UP. The antimicrobial susceptibility of UP and the predictors of CMP among UP infected patients were also analyzed. All patients were followed up at least for 6-months. Results Forty-nine patients (17.8%) showed urinary UP infection. Urinary UP serotyping showed the prevalence of seorvar-1, -3, -6 and -14 were 24.5%, 30.6%, 18.4% and 26.5%, respectively. 79.6% of the urinary UP positive patients accompanied vaginal UP infection. 22 patients of the cohort (8.0%) had CMP whereas serovars-3 and -14 accompanied CMP in 54.5% and 41.0% cases, respectively. No serovars-6 infection case had CMP. 26.4% of the cohort were infertile whereas 10.9% of these infertile patients were positive for urinary tract infection with UP serotype-3 or -14. Doxycycline, josamycin and pristinamycin were the most active antibiotics with the lowest rate of resistance (0.0%) for treating UP. At 1-month post-initial treatment with doxycycline, all UP serotypes were eradicated and no patient complained of urethral discomfort. However, simultaneous urinary and vaginal reinfection of serovar-3 (5 cases) and serovar-5 (1 case) were confirmed at 3-months post-initial doxycycline therapy. The logistic regression analyses revealed that serovars-3 [hazard ratio (HR) 1.354, P value 0.018] and -14 (HR 1.103, P value 0.046) were significantly associated with CMP in female patients having MH. Conclusions UP serovars-3 and -14 infections could be associated with CMP in female patients having MH. Doxycycline, josamycin and pristinamycin were effective for treating UP. Serovar-3 showed higher reinfection rate than other serotypes after antibiotics treatment.

Background: Kidney transplantation (KT) is regarded as the most effective treatment for end-stage renal disease. The annual number of KT cases in South Korea has in creased rapidly as more centers are implementing a transplantation program. The objective of this study was to determine clinical outcomes of the first 300 consecutive cases of KT in a single center. Methods: Clinical data of 300 cases of KT at Seoul National University Bundang Hos pital from January 2004 to March 2018 were obtained from a prospectively collected database and retrospectively reviewed. Results: The mean age of patients was 47.7±12.9 years, and 59% of patients were male. There were 225 living donors and 75 deceased donors. A total of 42 cases were from ABO-incompatible donors. During a mean follow-up of 68.6±43.5 months, 38 patients (12.7%) experienced rejection. The most common cause was acute T-cell mediat ed rejection (9.0%). Eighteen patients experienced graft loss. One-year and 5-year death-censored graft survival rates were 99% and 96.6%, respectively. One-year and 5-year patient survival rates were 98.3% and 96.6%, respectively. Multivariate analysis revealed that graft weight-to-recipient weight ratio and rejection were significant fac tors affecting graft survival. Conclusions: This single-center review demonstrates clinical outcomes comparable to other major centers. Such good outcomes were obtained by good patient selection, dedicated transplant physicians, and adequate use of immunosuppressive therapy.

To examine the diagnostic performance of Vesical Imaging-Reporting and Data System (VIRADS) and to find a quantitative indicator for predicting muscle layer invasion of bladder cancer. 3-T MRI of 82 patients performed before transurethral resection of bladder tumors or radical cystectomy between July 2018 and June 2019 were retrospectively analyzed. For one index lesion of each patient, two radiologists independently assigned VIRADS score and measured tumor-wall interface (contact length between tumor and bladder wall) on T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. Inter-reader agreement was assessed, and logistic regression analysis was performed to find indicators of muscle layer invasion. Comparison of indicators’ diagnostic performance was done with receiver operating characteristic (ROC) curve and generalized linear model analyses. Optimal cutoff point was determined by the Youden index J. Inter-reader agreement was at least substantial for VIRADS categorization (κ 0.77–0.81), and almost perfect for tumor-wall interface (intraclass correlation coefficient 0.88–0.90). Tumor-wall interface (odds ratio [OR] 1.90–2.00) and VIRADS score (OR 8.59–8.89) were independently associated with muscle layer invasion (p ≤ 0.02). For VIRADS, area under the ROC curve (AUROC) was 0.94, and the accuracy was 0.93 at score 3, the optimal threshold for predicting muscle layer invasion. Depending on the MRI sequence, tumor-wall interface showed AUROCs of 0.90–0.92 and accuracy of 0.84–0.90 at suggested thresholds (3 ± 0.3 cm). Tumor-wall interface showed insignificant differences in accuracy compared with VIRADS (p > 0.10), except as measured on diffusion-weighted images (p = 0.01). VIRADS is a good predictor of muscle layer invasion. As an independent quantitative indicator, tumor-wall interface may complement VIRADS to enhance prediction. • Vesical Imaging-Reporting and Data System (VIRADS) is a promising predictor of muscle invasion of bladder cancer with good reproducibility, as suggested by previous studies. • VIRADS score and the tumor-wall interface (curvilinear contact length between the tumor and the bladder wall) are independent predictors of muscle layer invasion. • As an easy-to-use quantitative indicator, tumor-wall interface is expected to be used as an indicator complementary to VIRADS, a qualitative indicator.

This study aimed to evaluate the oncological outcomes and post-implantation complications of the concurrent androgen deprivation therapy (ADT) with I-125 low-dose-rate (LDR)-prostate brachytherapy (sparse implantation technique: SIT) in comparison with the conventional non-ADT using whole gland brachytherapy (CWT). 302 localized prostate cancer (PCa) patients were treated with CWT (implantation dose: 145 Gy) and 215 patients were treated with SIT, which applied reduced implantation dose of 123.5 Gy. SIT group had ADT consisting of bicalutamide 50 mg/day plus 3-month depot (11.25 mg) of leuprolide acetate subcutaneously on the post-implantation day-0. Post-implantation complications and biochemical-recurrence-free-survival (BCRS) were compared between the two groups. After ADT, SIT group had 40.9% patients (40.9%) with prostate volume reduction between 20–30%. At 3-months post-implantation, SIT group presented significantly better IPSS than CWT group (p = 0.038). Both groups showed decrease in IIEF-5 score at 3-months post-implantation, but ST group showed significantly better mean IIEF-5 scores (13.5) than the CWT group (11.1) (p = 0.045). For 3-months post-implantation dosimetry, both groups showed no significant differences regarding D90 (CWT 156 Gy vs. SIT 152 Gy). CWT group had 3 patients with rectal toxicity ≥radiation therapy oncology group (RTOG) grade 2 and 1 patient with urinary toxicity ≥RTOG grade 2 whereas SIT group had no patient with urinary or rectal toxicity ≥RTOG grade 2. Kaplan-Meier analyses showed no significant differences regarding PCSS were observed between the two groups (p = 0.350). The SIT group showed compatible oncological outcomes to the CWT and relatively smaller number of post-implantation complications within low- and intermediate-risk PCa patients.

To investigate potential markers of the prostate cancer (PCa) Gleason score (GS), genetic arrays in 841 PCa patients were conducted followed by functional validation in PCa cell lines. A total of 841 PCa patients who received radical prostatectomy (RP) from November 2003 to July 2019 were enrolled. HumanExome BeadChip 12v1-1 (Illumina, Inc., San Diego, CA, USA) exomic arrays were performed on RP tissue samples. Unconditional logistic regression was used to calculate odds ratios to generate estimates of the relative risk of pathologic GS (≥8), SNPs with the highest association were selected and validated using PCa cell lines (PC3, LNCaP, 22Rv1 and DU145). Following transfection with target-gene siRNA, assays for cell viability, wound healing, and transwell invasion were performed. Mean age of enrolled subjects was 66.34 years and median PSA was 8.43 ng/mL. After RP, 122 patients (14.5%) had pathological Gleason scores ≥8. The results from genotyping with 242,186 SNPs by exomic array revealed that 4 SNPs (rs200944490, rs117555780, rs34625170, and rs61754877) were significantly associated with high pathological GS (≥8) within cut-off level to p &lt, 10−5. The most highly associated rs200944490 in ARRDC4 (p = 1.39 × 10−6) and rs117555780 in UBXN1 (p = 2.92 × 10−5) were selected for further validation. The knockdown of UBXN1 and ARRDC4 led to significantly reduced cell proliferation and suppressed migration and invasiveness in PCa cell lines. Epithelial mesenchymal transition (EMT) markers were significantly down-regulated in si-ARRDC4 and si-UBXN1-transfected cells. The expression levels of PI3K-phosphorylation and Akt phosphorylation and NF-κB were also suppressed following knockdown of UBXN1 and ARRDC4. The rs200944490 (ARRDC4) and rs117555780 (UBXN1) were identified as candidate markers predictive of PCa Gleason score which is strongly associated with cancer aggressiveness. Additional validation in future studies is warranted.

INTRODUCTION AND OBJECTIVE:Renal function after partial nephrectomy (PN) depends on a complex of clinical conditions including preoperative parenchymal quality, postop parenchymal quantity, and the...

Background We investigated prevalence of familial and hereditary prostate cancer (PCa) in Asian population, and compared clinical characteristics between familial and sporadic disease. Methods Pedigrees of 1102 patients who were treated for PCa were prospectively acquired. Clinical and pathologic characteristics and biochemical recurrence (BCR)-free survival were compared between familial PCa and sporadic PCa in patients who underwent radical prostatectomy (RP; n = 751). Results The prevalence of familial, first-degree familial, and hereditary PCa was found to be 8.4%, 6.7%, and 0.9%, respectively; similar result was obtained in patients who underwent RP (8.4%, 6.4%, and 0.9%). Patients with familial PCa were significantly younger than those with sporadic PCa (63.3 vs 65.6 years; P = .015). However, preoperative variables (prostate-specific antigen, clinical stage, biopsy Gleason score [GS], and percentage of positive biopsy cores) and postoperative variables (surgical GS, upgrading rate, pathologic stage, and percentage of tumor volume) did not correlate with family history (P range: .114-.982). Kaplan-Meier analysis of 5-year BCR-free survival revealed no significant difference between sporadic (82.7%), familial (89.4%; P = .594), and first-degree familial (87.1%; P = .774) PCa. Analysis of p53, Bcl-2, Ki67, and other immunohistochemistry biomarkers revealed that only increasing p53 expression and first-degree familial PCa approached significance (P = .059). Conclusion The prevalence of familial PCa was somewhat lower in the Asian population than in other ethnic groups. Clinical and pathologic variables and selected histologic biomarker abnormalities were not significantly different in patients with and without a family history of PCa. BCR-free survival following RP was also unaffected by family history.

Introduction Some previous studies reported recreational use of phosphodiesterase type 5 (PDE-5) inhibitors by ingesting the medicine with alcohol in patients with erectile dysfunction, but the rate of misuse in general population has never been researched. Aim To investigate the frequency of concomitant alcohol consumption with PDE-5 inhibitors in the general male population. We secondarily analyzed the influence of alcohol on PDE-5 inhibitor. Methods 325 men with erectile dysfunction (age 34–78) who received PDE-5 inhibitors at a single medical institution from January 2016–February 2018 were included in the study. All patients fulfilled a survey questionnaire assessing (i) average alcohol consumption amount, (ii) previous use of PDE-5 inhibitors with alcohol and purpose of concomitant alcohol use, (iii) and background knowledge about PDE-5 inhibitors' side effects. Main Outcomes Measures The main outcome measure was frequency of concomitant alcohol consumption with PDE-5 inhibitors in the general male population. Results Overall 148 patients committed concomitant alcohol use (group 1), and 177 patients did not (group 2). No significant differences were observed between 2 groups regarding types of PDE-5 inhibitors used and underlying disease. Group 2 had significantly more patients with the correct knowledge concerning concomitant alcohol use than group 1 (24.9% vs 13.5%). Group 1 had more patients with average alcohol consumption >15 drinks/week (64.8% vs 14.1%). The reasons for concomitant alcohol use were curiosity (35.1%), enhancing sexual desire (27%) and recommendation from friends (16.9%). Group 1 showed significantly greater complications, including headache (23.6% vs 7.3%) and facial flushing (69.6% vs 12.4%), than group 2. 1 patient in group 1 experienced severe chest discomfort and underwent coronary artery angiography, but no severe obstructive lesion was observed. Conclusion 45.5% of middle- to old-age men committed concomitant use of PDE-5 inhibitor with alcohol because of recreational purpose, and this alcohol abuse might lead to severe complications, including chest discomfort and dizziness.

AimThis study evaluated the prognosis and survival predictors for bladder urachal carcinoma (UC), based on large scale multicenter cohort with long term follow-up database.MethodsA total 203 patients with bladder UC treated at 19 hospitals were enrolled. Clinical parameters on carcinoma presentation, diagnosis, and therapeutic methods were reviewed for the primary cancer and for all subsequent recurrences. The stage of UC was stratified by Mayo and Sheldon pathological staging system. Oncological outcomes and the possible clinicopathological parameters associated with survival outcomes were investigated.ResultsThe mean age of the patients was 54.2 years. Among the total of 203 patients, stages I, II, III, and IV (Mayo stage) were 48 (23.8%), 108 (53.5%), 23 (11.4%), and 23 (11.4%), respectively. Gross hematuria and bladder irritation symptoms were the two most common initial symptoms. The mean follow-up period was 65 months, and 5-year overall survival rates (OS), cancer-specific survival rates (CSS), and recurrence-free survival rates (RFS) were 88.3, 83.1, and 63.9%, respectively. For the patients with Mayo stage ≥III, OS, CSS, and RFS were significantly decreased to 38.0, 35.2, and 28.4%, respectively. The higher pathological stage (Mayo stage ≥III, Sheldon stage ≥IIIc), positive surgical margin (PSM), and positive lymphovascular invasion (PLM) were independent predictors of shorter OS, CSS, and RFS.ConclusionThe pathological stage, PSM, and PLM were significantly associated with the survival of UC patients, emphasizing an importance of the complete surgical resection of tumor lesion.

Background To identify potential prognostic factors among patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6. Methods From 2003 to 2019, favorable intermediate risk patients who underwent radical prostatectomy were included in this study. All patients were evaluated preoperatively with MRI. Using PI-RADS scores, patients were divided into two groups, and clinic-pathological outcomes were compared. The impact of preoperative factors on significant pathologic Gleason score upgrading (≥ 4 + 3) and biochemical recurrence were assessed via multivariate analysis. Subgroup analysis was performed in patients with PI-RADS ≤ 2. Results Among the 239 patients, 116 (48.5%) were MRI-negative (PI-RADS ≤ 3) and 123 (51.5%) were MRI-positive (PI-RADS > 3). Six patients in the MRI-negative group (5.2%) were characterized as requiring significant pathologic Gleason score upgrading compared with 34 patients (27.6%) in the MRI-positive group (p Conclusions Among the patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6, preoperative MRI was capable of predicting significant pathologic Gleason score upgrading and biochemical recurrence. Especially, the patients with PI-RADS ≤ 2 and low biopsy tumor length could be a potential candidate to active surveillance.

Aims The purpose of this study is to evaluate an aggregate influence of prostate cancer (PCa) susceptibility variants on the development of PCa in Korean men by using the polygenic risk score (PRS) approach. Methods An analysis of 1,001 cases of PCa and 2,641 controls was performed to: (i) identify potential PCa-related risk loci in Koreans and (ii) validate the cumulative association between these loci and PCa using the PRS. Subgroup analyses based on risk stratification were conducted to better characterize the potential correlation to key PCa-related clinical outcomes (e.g., Gleason score, prostate-specific antigen levels). The results were replicated using 514 cases of PCa and 548 controls from an independent cohort. Results Genome-wide association analysis from our discovery cohort revealed 11 candidate single-nucleotide polymorphisms (SNPs) associated with PCa showing statistical significance of p < 5.0 × 10–5. Seven variants were located at 8q24.21 (rs1016343, rs16901979, and rs13252298 in PRNCR1; rs4242384, rs7837688, and rs1447295 in CASC8; and rs1512268 in NKX3). Two variants located within HNF1B (rs7501939 and rs4430796) had a significant negative association with PCa risk [odds ratio (OR) = 0.717 and 0.747, p = 6.42 × 10–7 and 3.67 × 10–6, respectively]. Of the six independent SNPs that remained after linkage disequilibrium (LD) pruning, the top four SNPs best predicted PCa risk with an area under the receiver operating characteristic curve (AUC) of 0.637 (95% CI: 0.582–0.692). Those with top 25% polygenic risk had a 4.2-fold increased risk of developing PCa compared with those with low risk. Conclusion Eleven PCa risk variants in Korean men were identified; PRSs of a subset of these variants could help predict PCa susceptibility.

OBJECTIVES To investigate the oncological significance of a robot-assisted radical cystectomy (RARC)-related pentafecta in patients with bladder cancer. PATIENTS AND METHODS Using the KORARC database, which includes data from 12 centres, data from 730 patients who underwent RARC between April 2007 and May 2019 were prospectively collected and retrospectively analysed. Pentafecta was achieved if patients met all of the following criteria: (i) negative soft tissue surgical margin; (ii) ≥16 lymph nodes removed; (iii) no major complications (Clavien-Dindo grade 3-5) within 90 days; (iv) no clinical recurrence within the first 12 months; and (v) no ureteroenteric stricture. Patients were divided into two groups according to pentafecta attainment, and a comparison of overall survival (OS) and cancer-specific survival (CSS) using multivariate Cox proportional analysis was then carried out. RESULTS Of the 730 patients included in this analysis, 208 (28.5%) attained the RARC pentafecta; the remaining 522 (71.5%) did not. The mean age of the patients was 64.67 years, 85.1% were men, 53.6% received a conduit, 37.7% received orthotopic neobladders and the total complication rate was 57.8%. Those who attained the pentafecta received more neobladders (P = 0.039), were more likely to be treated with the intracorporeal technique (P < 0.001), had longer operating times (P = 0.020) and had longer console time (P = 0.021) compared with those who did not attain the pentafecta. Over a mean of 31.1 months of follow-up, the pentafecta attainment group had significantly higher OS and CSS rates compared with the non-attainment group (10-year OS 70.4% vs 58.1%, respectively [P = 0.016]; 10-year CSS 87.8% vs 70.0%, respectively [P = 0.036]). Multivariate analysis showed that the RARC pentafecta was a significant predictor of overall mortality (hazard ratio 0.561; P = 0.038). CONCLUSIONS Patients who attained the RARC pentafecta had significantly better survival outcomes compared with those who did not. These criteria could be used to standardize assessment of the surgical quality of RARC. In the future, a similar study using an independent cohort is warranted to confirm our results.

The objective of this study was to evaluate risk factors for bacillus Calmette–Guerin-induced prostatitis in patients with non-muscle invasive bladder cancer following bacillus Calmette–Guerin therapy. Clinical findings from patients with non-muscle invasive bladder cancer who underwent multi-parametric magnetic resonance imaging before transurethral resection of bladder tumor and post-bacillus Calmette–Guerin therapy from March 2004 to August 2018 were evaluated. The population was grouped into patients with or without newly developed lesions on multi-parametric magnetic resonance imaging performed 3 months after bacillus Calmette–Guerin instillation. Patients with prostate-specific antigen levels ≥ 4 ng/mL or prostate cancer were excluded. Univariable and multivariable analyses were performed to determine the predictors of prostate lesions in patients with prior bacillus Calmette–Guerin exposure. Post bacillus Calmette–Guerin-induced prostatitis was found in 50 of the 194 patients (25.8%). No significant differences were observed between the groups except for prostate volumes (33.8 mL vs. 30.8 mL, P = 0.012) and body mass index (25.2 kg/m2 vs. 24.1 kg/m2, P = 0.044). After bacillus Calmette–Guerin exposure, no significant differences in prostate-specific antigen levels, international prostate symptom scores, or post-voiding residual volume were noted. Multivariable regression analysis showed that body mass index (odds ratio, OR = 1.115, P = 0.038) and prostate volume (OR = 3.080, P = 0.012) were significant predictors of post-bacillus Calmette–Guerin prostate lesions. Body mass index and prostate volume may be clinical predictors of prostate lesions after bacillus Calmette–Guerin exposure. Awareness of potential risk factors for this entity should contribute to the clinical decision-making process for patients following bacillus Calmette–Guerin therapy.

INTRODUCTION AND OBJECTIVE:We aimed to evaluate the prognostic value of seminal vesicle invasion (SVI) on preoperative multiparametric MRI (mpMRI) in pathological T3b prostate cancer (PCa).METHODS:...

INTRODUCTION AND OBJECTIVE:Preoperative chronic kidney disease (CKD) status may affect disease outcomes in patients with upper tract urothelial carcinoma (UTUC). We evaluated the impact of preopera...

IntroductionCardiovascular disease (CVD) in patients with diabetes is the leading cause of death. Finding early biomarkers for detecting asymptomatic patients with CVD can improve survival. Recently, plasma proteomics—targeted selected reaction monitoring/multiple reaction monitoring analyses (MRM)—has emerged as highly specific and sensitive tools compared with classic ELISA methods. The objective was to identify differentially regulated proteins according to the severity of the coronary artery atherosclerosis.Research design and methodsA discovery cohort, a verification cohort and a validation cohort consisted of 18, 53, and 228 subjects, respectively. The grade of coronary artery stenosis was defined as a percentage of luminal stenosis of the major coronary arteries. Participants were divided into six groups, depending on the presence of diabetes and the grade of coronary artery stenosis. Two mass spectrometric approaches were employed: (1) conventional shotgun liquid chromatography tandem mass spectrometry for a discovery and (2) quantitative MRM for verification and validation. An analysis of the covariance was used to examine the biomarkers’ predictivity beyond conventional cardiovascular risks.ResultsA total of 1349 different proteins were identified from a discovery cohort. We selected 52 proteins based on the tandem mass tag quantitative analysis then summarized as follows: chemokine (C-X-C motif) ligand 7 (CXCL7), apolipoprotein C-II (APOC2), human lipopolysaccharide-binding protein (LBP) and dedicator of cytokinesis 2 (DOCK2) in diabetes; CXCL7, APOC2, LBP, complement 4A (C4A), vitamin D-binding protein (VTDB) and laminin β1 subunit in non-diabetes. Analysis of covariance showed that APOC2, DOCK2, CXCL7 and VTDB were upregulated and C4A was downregulated in patients with diabetes showing severe coronary artery stenosis. LBP and VTDB were downregulated in patients without diabetes, showing severe coronary artery stenosis.ConclusionWe identified significant associations between circulating APOC2, C4A, CXCL7, DOCK2, LBP and VTDB levels and the degree of coronary artery stenosis using the MRM technique.

To evaluate the effectiveness of an antibiotic regimen for prostate biopsy by analyzing patients who were hospitalized because of complications after transrectal ultrasound-guided prostate biopsy.We reviewed retrospectively the medical records of 10,339 patients who underwent transrectal ultrasound-guided prostate biopsy at our institution from May 2003 to April 2017. We excluded patients with low quality data. All patients underwent urine culture before transrectal ultrasound-guided prostate biopsy and received intravenous antibiotic agents 30-60 minutes before biopsy. Patients were either given prophylactic quinolone or cephalosporin (second or third generation). Clinicopathologic factors including patient age, antibiotic regimen, number of biopsy cores, body mass index, prostate specific antigen, prostate volume, and infection-related complications that required hospitalization were subsequently analyzed.A total of 9,487 patients were included in the final analysis, of whom 33 patients (0.35%) were hospitalized because of infection-related complications. Infection-related hospitalization rates were lower in patients who received cephalosporin (0.2%) than in patients who received quinolone (1.59%). At our institution, cephalosporin has been used predominantly to prevent post-biopsy infections since February 2013. Only five patients (0.12%) developed infection-related complications of the 3,863 patient who underwent transrectal ultrasound-guided prostate biopsy since February 2013. Multivariable analysis revealed that use of second- or third-generation cephalosporin was the only independent predictor of infection-related complications.Implementing an effective antibiotic prophylaxis regimen at our institution by using second- or third-generation cephalosporin could reduce infection-related complications after transrectal ultrasound-guided prostate biopsy.

It has not been clearly proved in real practice whether early rehabilitation with phosphodiesterase type 5 inhibitors starting immediately after radical prostatectomy improves erectile function recovery more effectively than delayed treatment with the same regimen. We performed a prospective randomized trial to identify this.Patients with prostate cancer and an IIEF-5 (International Index of Erectile Function-5) preoperative score of 17 or greater were randomly assigned to receive sildenafil 100 mg regularly twice per week for 3 months immediately after urethral catheter removal as the early group or only 3 months after nerve sparing robot-assisted laparoscopic radical prostatectomy as the delayed group. The study primary end point was the full erectile function recovery rate, defined as an IIEF-5 score of 17 or greater, during the 12 months.Of the 120 randomized patients the proportion who achieved full recovery was significantly higher during the 12 months in the early group than in the delayed group (β = 0.356, p0.001, generalized estimating equation). After 9 months postoperatively the proportion of patients who achieved full recovery steadily increased to 41.4% at 12 months in the early group while patients in the delayed group showed no further improvement. Thus, full recovery was achieved in only 17.7% of patients at 12 months. Only early sildenafil treatment independently improved full recovery at 12 months (HR 2.943, p = 0.034).Our trial provides clinical data to suggest that earlier rehabilitation with phosphodiesterase type 5 inhibitors can contribute to the recovery of erectile function after radical prostatectomy in the clinical setting.

Lipid metabolism has been suggested to be associated with clinical outcomes of renal cell carcinoma (RCC). In this study, we aimed to investigate the relationship between preoperative cholesterol level (PCL) and postoperative outcomes of patients with localized RCC.We retrospectively analyzed the data of 5022 patients surgically treated for nonmetastatic RCC. According to the receiver operating curve of PCL for cancer-specific mortality, we stratified the patients into 2 groups by using a cutoff value of 161 mg/dL. The propensity scores for having low PCL were calculated, and the low PCL group was matched with the high PCL group at a 1:2 ratio. The oncological profiles and postoperative survival of patients were compared.A low cholesterol level was significantly associated with adverse pathologic findings, such as higher pathologic stage (P .001) and large tumor size (P = .002). Furthermore, the low cholesterol group showed significantly worse progression-free, cancer-specific, and overall survival (all P values .001) compared with the high cholesterol group. Multivariate analysis exhibited a higher PCL as an independent predictor of better progression-free (P .001), cancer-specific (P = .018), and overall survival (P = .001) after matching. Subgroup analysis according to tumor histology revealed that PCL had a significant relationship with patients' survival in clear cell RCC, but not in non-clear cell RCC.Decreased PCL was significantly associated with worse pathologic outcomes and also inferior postoperative survival in patients with localized RCC; however, those relationships were significant only in clear cell subtypes.

We investigated the surgical efficiency and cutoff criteria to determine whether retrograde intrarenal surgery (RIRS) or supine miniaturized percutaneous nephrolithotomy (MPCNL) is appropriate for managing renal stones with a mean size10 mm.Data of a single session RIRS or supine MPCNL were collected in a prospective, observational study. Change point analysis with a cumulative sum of ordered value of fragmentation efficiency and stone size was used to detect the point at which the statistical properties of a sequence of observation change.A total of 310 RIRS and 66 MPCNL cases were included. No differences in patient characteristics were observed between the groups. Stone burden, fragmentation efficiency, stone distribution, and the presence of staghorn stones were higher in the MPCNL group than the RIRS group. Stone-free rates and complication rates were not different. The fragmentation efficiency increased to 40.4 mL/min, at which the stone size in the RIRS group was 19.1 mm. The efficiency was decreased after the peak point and became the same at the stone size 30 mm with 10 mm in RIRS group. The fragmentation efficiency in the MPCNL group continuously increased until the size of 35.1 mm.RIRS shows the highest efficiency at the maximal diameter of 19.1 mm and volume of 15,000 mm

Although partial nephrectomy (PN) is the standard treatment for localized clinical T1a renal cell carcinoma (RCC), treatment of larger renal tumors is controversial. We evaluated the oncological outcomes and perioperative complications after radical and PN for RCC ≥4cm.We retrospectively analyzed the data of 2,373 patients surgically treated for nonmetastatic RCC with clinical T1b or T2 (≥4cm). The propensity scores for surgery type were calculated, and the partial group was matched to the radical group in a 1:3 ratio. The oncological outcomes were compared using Kaplan-Meier analysis and multivariate Cox regression models were used to identify the independent predictors of progression-free, cancer-specific, and overall survival.All differences in preoperative clinical characteristics disappeared after matching. There were no significant differences in progression-free, cancer-specific, or overall survival between the partial and radical groups in the matched cohort. The patients' age, tumor size, cellular grade, and pathologic stage were independent predictors for all 3 survival outcomes. However, early complications (30d postoperative) were significantly more common in the partial group (P0.001). In a subgroup analysis of the patients with clinical T2 stage, there were no significant differences in all 3 survival outcomes.The partial and radical nephrectomy groups had equivalent oncological outcomes. Although the early complication rate was significantly higher after PN, it should be considered as a valuable treatment option even in patients with clinical T1b or higher RCC.

// Jung Ku Jo 1, * , Jong Jin Oh 2, * , Yong Tae Kim 1 , Hong Sang Moon 3 , Hong Yong Choi 3 , Seunghyun Park 4 , Jin-Nyoung Ho 5 , Sungroh Yoon 4 , Hae Young Park 1 and Seok-Soo Byun 2 1 Department of Urology, Hanyang University Hospital, Seoul, Korea 2 Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea 3 Department of Urology, Hanyang University Guri Hospital, Guri-si, Korea 4 Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea 5 Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea * These authors contributed equally to this work Correspondence to: Seok-Soo Byun, email: ssbyun@snubh.org Hae Young Park, email: nopcme@hanyang.ac.kr Keywords: metastasis, prostate cancer, castration, genetic variation Received: December 14, 2016 Accepted: May 01, 2017 Published: May 30, 2017 ABSTRACT Background: Genetic variation which related with progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT) has not been elucidated in patients with metastatic prostate cancer (mPCa). Therefore, we assessed the association between genetic variats in mPCa and progession to CRPC. Results: Analysis of exome genotypes revealed that 42 SNPs were significantly associated with mPCa. The top five polymorphisms were statistically significantly associated with metastatic disease. In addition, one of these SNPs, rs56350726, was significantly associated with time to CRPC in Kaplan-Meier analysis (Log-rank test, p = 0.011). In multivariable Cox regression, rs56350726 was strongly associated with progression to CRPC (HR = 4.172 95% CI = 1.223-14.239, p = 0.023). Materials and Methods: We assessed genetic variation among 1000 patients with PCa with or without metastasis, using 242,221 single nucleotide polymorphisms (SNPs) on the custom HumanExome BeadChip v1.0 (Illuminam Inc.). We analyzed the time to CRPC in 110 of the 1000 patients who were treated with ADT. Genetic data were analyzed using unconditional logistic regression and odds ratios calculated as estimates of relative risk of metastasis. We identified SNPs associated with metastasis and analyzed the relationship between these SNPs and time to CRPC in mPCa. Conclusions: Based on a genetic variation, the five top SNPs were observed to associate with mPCa. And one (SLC28A3, rs56350726) of five SNP was found the association with the progression to CRPC in patients with mPCa.

// Jong Jin Oh 1 , Seunghyun Park 2, 3 , Sang Eun Lee 1 , Sung Kyu Hong 1 , Sangchul Lee 1 , Tae Jin Kim 1 , In Jae Lee 1 , Jin-Nyoung Ho 1, 4 , Sungroh Yoon 2 and Seok-Soo Byun 1 1 Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea 2 Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea 3 School of Electrical Engineering, Korea University, Seoul, Korea 4 Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea Correspondence to: Seok-Soo Byun, email: ssbyun@snubh.org Keywords: prostate cancer, genetic risk score, recurrence, predictive value Received: April 12, 2017 Accepted: May 07, 2017 Published: May 26, 2017 ABSTRACT Purpose: To investigate the genetic risk score (GRS) from a large-scale exome-wide association study as a tool of prediction for biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer (PCa). Results: The 16 SNPs were selected as significant predictors of BCR. The GRS in men experiencing BCR was -1.21, significantly higher than in non-BCR patients (–2.43) ( p < 0.001). The 10-year BCR-free survival rate was 46.3% vs. 81.8% in the high-versus low GRS group, respectively ( p < 0.001). The GRS was a significant factor after adjusting for other variables in Cox proportional hazard models (HR:1.630, p < 0.001). The predictive ability of the multivariate model without GRS was 84.4%, increased significantly to 88.0% when GRS was included ( p = 0.0026). Materials and Methods: Total 912 PCa patients were enrolled who had received RP and genotype analysis using Exome chip (HumanExome BeadChip). Genetic results were obtained by the methods of logistic regression analysis which measured the odds ratio (OR) to BCR. The GRS was calculated by the sum of each weighted-risk allele count multiplied by the natural logarithm of the respective ORs. Survival analyses were performed using the GRS. We compared the accuracy of separate multivariate models incorporating clinicopathological factors that either included or excluded the GRS. Conclusions: GRS had additional predictive gain of BCR after RP in PCa. The addition of personally calculated GRS significantly increased the BCR prediction rate. After validation of these results, GRS of BCR could be potential biomarker to predict clinical outcomes.

Background The obesity and lipid metabolism were previously proposed to be related with the clinical outcomes of metastatic renal cell carcinoma (mRCC). We tried to investigate the relationship between preoperative cholesterol level (PCL) and survival outcomes in patients with mRCC. Methods We analysed the data of 244 patients initially treated with cyto-reductive nephrectomy after being diagnosed with mRCC. Patients were stratified into two groups according to the PCL cut-off level of 170 mg/dL. The postoperative survival rates were compared using Kaplan-Meier analysis and the possible predictors of patients’ cancer-specific survival (CSS) and overall survival (OS) were tested using multivariate Cox-proportional hazard models. Results The low cholesterol group showed significantly worse postoperative CSS (p = 0.013) and OS (p = 0.009) than the high cholesterol group. On multivariate analysis, low PCL was revealed as an independent predictor of worse CSS (hazard ratio [HR], 2.162; 95% CI, 1.221–3.829; p = 0.008) and OS (HR, 2.013; 95% CI, 1.206–3.361; p = 0.007). Subsequent subgroup analysis showed that these results were maintained in the clear cell subgroup but not in the non-clear cell subgroup. Conclusion Decreased PCL was significantly correlated with worse survival outcomes in patients with mRCC treated with cytoreductive nephrectomy. The underlined mechanism is still uncharted and requires further investigation.

// Jong Jin Oh 1, * , Soo Ji Lee 2, * , Joo-Yeon Hwang 3, * , Dokyoon Kim 4 , Sang Eun Lee 1 , Sung Kyu Hong 1 , Jin-Nyoung Ho 1, 5 , Sungroh Yoon 6 , Joohon Sung 2 , Wun-Jae Kim 7 and Seok-Soo Byun 1 1 Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea 2 Complex Disease and Genome Epidemiology Branch, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea 3 Division of Structural & Functional genomics, Center for Genome Science, Korean National Institute of Health, KCDC, Korea 4 Department of Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA 5 Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea 6 Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea 7 Department of Urology, Chung Buk National University Hospital, Cheongju, Korea * Authors contributed equally in this work Correspondence to: Seok-Soo Byun, email: ssbyun@snubh.org Wun-Jae Kim, email: wjkim@chungbuk.ac.kr Keywords: prostate, prostate cancer, exome, Korean Received: December 15, 2016 Accepted: February 15, 2017 Published: March 24, 2017 ABSTRACT Purpose: To investigate exome-wide genetic variants associated with prostate cancer (PCa) in Koreans and evaluate the discriminative ability by the genetic risk score (GRS). Patients and methods: We prospectively recruited 1,001 PCa cases from a tertiary hospital and conducted a case-control study including 2,641 healthy men (Stage I). Participants were analyzed using HumanExome BeadChip. For the external validation, additionally enrolled 514 PCa cases and 548 controls (independent cohort) were analyzed for the identified single nucleotide polymorphisms (SNPs) of Stage I (Stage II). The GRS was calculated as a non-weighted sum of the risk allele counts and investigated for accuracy of prediction of PCa. Results: the mean age was 66.3 years, and the median level of prostate specific antigen (PSA) was 9.19 ng/ml in PCa cases. In Stage I, 4 loci containing 5 variants (rs1512268 on 8p21.2; rs1016343 and rs7837688 on 8q24.21; rs7501939 on 17q12, and rs2735839 on 19q13.33) were confirmed to reach exome-wide significance (p

INTRODUCTION AND OBJECTIVE:To identify whether the concurrent systematic biopsy (SB) is still necessary in the magnetic resonance imaging fusion-targeted biopsy (MRIFTB) eraMETHODS:Total of 714 men...

Since prostate cancer is highly heritable, common variants associated with prostate cancer have been studied in various populations, including those in Korea. However, rare and low-frequency variants have a significant influence on the heritability of the disease. The contributions of rare variants to prostate cancer susceptibility have not yet been systematically evaluated in a Korean population. In this work, we present a large-scale exome-wide rare variant analysis of 7,258 individuals (985 cases with prostate cancer and 6,273 controls). In total, 19 rare variant loci spanning 7 genes contributed to an association with prostate cancer susceptibility. In addition to replicating previously known susceptibility genes (e.g., CDYL2, MST1R, GPER1, and PARD3B), 3 novel genes were identified (FDR q ENTPD3-AS1, LOC102724438, and protein-coding gene SPATA3. Additionally, 6 pathways were identified based on identified variants and genes, including estrogen signaling pathway, signaling by MST1, IL-15 production, MSP-RON signaling pathway, and IL-12 signaling and production in macrophages, which are known to be associated with prostate cancer. In summary, we report novel genes and rare variants that potentially play a role in prostate cancer susceptibility in the Korean population. These observations demonstrated a path towards one of the fundamental goals of precision medicine, which is to identify biomarkers for a subset of the population with a greater risk of disease than others.