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Purpose: To describe the incidence and mortality of upper tract urothelial carcinoma (UTUC) from 2002-2020 using data from the Korean National Health Insurance Service, which contains data from the entire Korean population., Materials and Methods: Reimbursement records for 43,255 patients diagnosed with primary UTUC (according to the International Classification of Disease 10th revision code C65 and C66) between 2002-2020 were retrieved. The study period was split into four: period I (2002-2005), period II (2006-2010), period III (2011-2015), and period IV (2016-2020). Trends were quantified by calculating the annual percentage change (APC). Mortality data were obtained from the Statistics Korea., Results: From 2002-2020, the incidence of UTUC in Korea increased gradually from 9.34 to 11.40 per 100,000 person-years. Although there was a male predominance, the male to female ratio did not change significantly over time; however, age at the time of diagnosis, the comorbidity index, and the proportion of patients undergoing open/laparoscopic surgery increased significantly over time. There was a modest improvement in 5-year survival (both all cause- and cancer-specific) over the study period. Multivariate analysis identified age at diagnosis, sex, the comorbidity index, and open/laparoscopic surgery as being associated with survival., Conclusions: Between 2002 and 2020, the incidence of UTUC in Korea showed a general upward trend; however, survival outcomes have improved. These representative datasets from the Korean population might provide crucial information that enables clinicians to better understand of the epidemiology of UTUC in Korea., Competing Interests: Mina Kim and Hoseob Kim are employees of Hanmi Pharmaceutical Co., Ltd., which had no influence on the present work. The other authors have nothing to disclose., (© The Korean Urological Association.)

Purpose: T1 high grade (T1HG) bladder cancer (BC) is a type of non-muscle invasive BC (NMIBC) that is recognized as an aggressive subtype with a heightened propensity for progression. Current risk stratification methods for NMIBC rely on clinicopathological indicators; however, these approaches do not adequately capture the aggressive nature of T1HG BC. Thus, new, more accurate biomarkers for T1HG risk stratification are needed. Here, we enrolled three different patient cohorts and investigated expression of collagen type VI alpha 1 ( COL6A1 ), a key component of the extracellular matrix, at different stages and grades of BC, with a specific focus on T1HG BC., Materials and Methods: Samples from 298 BC patients were subjected to RNA sequencing and real-time polymerase chain reaction., Results: We found that T1HG BC and muscle invasive BC (MIBC) exhibited comparable expression of COL6A1 , which was significantly higher than that by other NMIBC subtypes. In particular, T1HG patients who later progressed to MIBC had considerably higher expression of COL6A1 than Ta, T1 low grade patients, and patients that did not progress, highlighting the aggressive nature and higher risk of progression associated with T1HG BC. Moreover, Cox and Kaplan-Meier survival analyses revealed a significant association between elevated expression of COL6A1 and poor progression-free survival of T1HG BC patients (multivariate Cox hazard ratio, 16.812; 95% confidence interval, 3.283-86.095; p=0.001 and p=0.0002 [log-rank test])., Conclusions: These findings suggest that COL6A1 may be a promising biomarker for risk stratification of T1HG BC, offering valuable insight into disease prognosis and guidance of personalized treatment decisions., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Purpose: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data., Materials and Methods: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded., Results: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups., Conclusions: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions., Competing Interests: SEY and SYK are employees of Janssen Korea Ltd. SEY was involved in study design, interpretation, funding, administrative support, and study supervision. SYK was involved in the statistical analysis and interpretation of the data. TWK declares participation in a Data Safety Monitoring Board or Advisory Board at Janssen. The remaining authors have nothing to disclose., (© The Korean Urological Association.)

Purpose: Tumor microRNAs (miRNAs) are released to biofluids directly or indirectly. Although urinary miRNAs are promising non-invasive biomarkers for the diagnosis of prostate cancer (PCa), their clinical application is challenging for technical reasons. We examined the efficacy of urinary hsv2-miR-H9 to hsa-miR-3659 ratio as a non-invasive diagnostic biomarker of PCa., Materials and Methods: The expression of urinary miRNAs was quantified by real-time PCR in 116 samples from 53 patients with benign prostatic hyperplasia (BPH) and 63 patients with PCa. The miRNA expression ratio was calculated using an upregulated miRNA (hsv2-miR-H9) as the numerator and a downregulated miRNA (hsa-miR-3659) as the denominator., Results: The urinary miR-H9 to miR-3659 ratio was significantly higher in PCa than in BPH controls (p<0.001). The diagnostic accuracy of the urinary miRNA expression ratio was comparable with that of prostate-specific antigen (PSA) (receiver operating characteristic [ROC] curve comparison, p=0.287). The area under the curve for urinary miRNA expression ratio was 0.862 and that for PSA was 0.642 in the "PSA gray zone" (3-10 ng/mL) (ROC curve comparison, p=0.034). The use of the urinary miRNA expression ratio would have prevented 70.6% of unnecessary prostate biopsies; however, 28.6% of PCa cases could be missed in patients within the PSA gray zone., Conclusions: The expression ratio of urinary miR-H9 to miR-3659 could be a relevant non-invasive biomarker for PCa diagnosis, particularly for patients within the PSA gray zone., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Purpose: Few studies have demonstrated the clinical significance of pretreatment serum albumin and globulin in prostate cancer (PCa). This study evaluated the association between the pretreatment albumin to globulin ratio (AGR) and clinicopathologic characteristics of nonmetastatic PCa in a large multicenter setting in Korea., Materials and Methods: This study involved 742 patients with nonmetastatic PCa who underwent radical prostatectomy (RP) in seven institutions between January 2011 and December 2012. The AGR was calculated as follows: albumin/(total protein-albumin). Patients were divided into low and high AGR groups by a cutoff value from a receiver operating characteristic curve analysis., Results: The best cutoff for the AGR was set at 1.53. The area under the curve of the AGR was 0.624 (95% confidence interval, 0.557-0.671; p<0.001). Patients who had a lower pretreatment AGR (<1.53) were identified as the low AGR group (n=398, 53.6%) and the remaining patients as the high AGR group (n=344, 46.4%). Preoperative AGR was significantly lower in patients with non-organ-confined disease (≥pT3) than in those with organ-confined disease (≤pT2) (p<0.001). The low AGR group had higher aggressive pathologic Gleason scores (pGS) (≥8) than did the high AGR group (p=0.016). Furthermore, the AGR was an independent prognostic factor for high pGS (≥8) and non-organ-confined disease (≥pT3), according to multivariate logistic regression analysis., Conclusions: A low AGR was closely associated with nonconfined disease (≥pT3) and high pGS (≥8). AGR can be a useful serological marker for predicting adverse pathology in patients with nonmetastatic PCa who undergo RP., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Molecular markers detected in urine may improve our understanding of the evolution of bladder cancer (BCa) and its micro- and macroenvironment. Detection of such markers will identify disease earlier, allow stratification of patients according to risk, and improve prognostication and prediction of outcomes, thereby facilitating targeted therapy. However, current guidelines have yet to embrace such markers for routine management of BCa, and most research studies have focused on urine-based tumor markers. In this review, we summarize known urinary biomarkers for BCa and highlight newly identified molecules. We then discuss the challenges that must be overcome to incorporate these markers into clinical care., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Purpose: We aimed to determine the influence of nutritional status on urinary metabolic abnormalities and stone recurrence in patients with urolithiasis., Materials and Methods: We analyzed data for 464 stone-formers and 464 propensity-score-matched control patients that had been collected between 2003 and 2015. Nutritional status was evaluated by use of the Controlling Nutritional Status (CONUT) score, and patients were placed into two CONUT score categories (0-1 and ≥2). Serum and 24-hour urinary metabolites were evaluated in 464 stone-formers. Kaplan-Meier and multivariate Cox regression analyses were performed to assess the influence of nutritional status on stone recurrence. Stone recurrence was defined as radiographic appearance of new stones during the follow-up period., Results: Stone-formers showed a higher prevalence of poor nutrition (CONUT score ≥2) than did the propensity-score-matched control patients (p<0.001). Stone-formers who had poor nutritional status had significantly lower 24-hour urinary calcium but higher oxalate excretion (each p<0.05). Kaplan-Meier estimates demonstrated that stone-formers with poor nutritional status also experienced stone recurrence more rapidly (log-rank test, p=0.014). Multivariate Cox regression revealed that poor nutritional status was independently associated with stone recurrence (hazard ratio, 1.736; 95% confidence interval, 1.041-2.896; p=0.034)., Conclusions: The CONUT score, an easily measured immunonutritional biomarker, is independently associated with a higher risk for stone recurrence in patients with urolithiasis. This implies that not only dietary excess, but also undernourished status, may be associated with aberrations in urine physicochemistry and stone recurrence., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Purpose: P21-activated kinase 4 (PAK4), a serine/threonine kinase that regulates a number of fundamental cellular processes, has been suggested as a prognostic factor for various human tumors. The aim of the present study was to evaluate the clinical implications of phospho-Ser474 PAK4 (pPAK4 S474 ), an activated form of PAK4, in surgically treated renal cell carcinoma (RCC)., Materials and Methods: Samples from 131 patients with surgically treated RCC were immunostained to detect PAK4 and pPAK4 S474 . Expression of PAK4 and pPAK4 S474 was compared with clinicopathological characteristics and survival after nephrectomy., Results: PAK4 and pPAK4 S474 were expressed predominantly in the nucleus. Overall, 57.3% (75/131) and 24.4% (29/119) of specimens exhibited high expression of pPAK4 S474 and PAK4, respectively. High expression of pPAK4 S474 was associated with adverse pathologic characteristics, including advanced tumor stage and grade (p=0.036 and p=0.002, respectively), whereas this association was not significant for PAK4 expression (each p>0.05). Kaplan-Meier estimates showed that high expression of pPAK4 S474 was associated with shorter recurrence-free survival in a subgroup with localized RCC and with cancer-specific survival in the total RCC cohort (log-rank test: p=0.001 and p=0.005, respectively), whereas PAK4 expression was not. Multivariate Cox regression analysis identified that high pPAK4 S474 expression was an independent predictor of recurrence in the subgroup with localized RCC., Conclusions: pPAK4 S474 may be a more accurate prognostic factor than total PAK4 in RCC patients. This marker would be useful for identifying patients with pathologically localized disease who may require further interventions., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs and are involved in the development, proliferation, and pathogenesis of prostate cancer (PCa). Urinary miRNAs are promising non-invasive biomarkers for PCa diagnosis because of their stability in urine. Here, we evaluated the diagnostic value of urinary miR-1913 to miR-3659 ratio in PCa patients and benign prostate hyperplasia (BPH) controls., Materials and Methods: Candidate miRNAs were identified from urinary microarray data and tested by real-time PCR. The urinary miR-1913 to miR-3659 expression ratio was selected and tested in 83 urine samples (44 PCa and 39 BPH) to confirm its validity as a non-invasive diagnostic biomarker for PCa., Results: The expression ratio of urinary miR-1913 to miR-3659 was significantly higher in PCa than in BPH (p=0.002) and showed a higher area under the receiver operating characteristic curve than prostate-specific antigen (PSA; 0.821 vs. 0.518) in patients within the PSA gray zone (tPSA: 3-10 ng/mL), with sensitivity of 75.0% and specificity of 78.6% (p=0.003)., Conclusions: The urinary miR-1913 to miR-3659 expression ratio was increased in PCa and may serve as a useful supplemental biomarker to PSA for the diagnosis of PCa, particularly in patients within the PSA gray zone., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Purpose: Basal metabolic rate (BMR) is an indicator of overall body metabolism and may portend unique aberrations in urine physico-chemistry and stone recurrence. The present study examined the effect of predicted BMR on 24 hours urinary metabolic profiles and stone recurrence in obese stone patients., Materials and Methods: Data from 308 obese patients (body mass index [BMI] ≥30 kg/m²) diagnosed with urinary stone disease between 2003 and 2015 were analyzed retrospectively. BMR was calculated using the Harris-Benedict equation, and patients were classified into two predicted BMR categories (<1,145 kcal/day, ≥1,145 kcal/day). Urinary metabolic parameters and risk of stone recurrence were compared between the two groups., Results: The high BMR group was more likely to be younger and female, and to have a high BMI and lower incidence of diabetes than the low BMR group (each p<0.05). There was a positive correlation between BMR and 24 hours urinary sodium, uric acid, and phosphate excretion. The amounts of stone-forming constituents such as calcium and uric acid were significantly higher in the high BMR group. Kaplan-Meier estimates showed that the high BMR group had a significantly shorter stone recurrence-free period than the low BMR group (log-rank test, p<0.001). Multivariate Cox regression analyses revealed that predicted BMR was an independent factor of stone recurrence (hazard ratio, 2.759; 95% confidence interval, 1.413-5.386; p=0.003)., Conclusions: BMR may be an easily measured parameter that can be used to identify risk of stone recurrence in obese stone patients., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Purpose: The aim of this study was to identify a noninvasive urinary marker for prostate cancer (PCa) diagnosis and to validate the clinical performance of this novel urinary mRNA signature using the droplet digital polymerase chain reaction (ddPCR) approach., Materials and Methods: A gene expression microarray (HT-12, Illumina Inc., USA) was used to identify genes differentially expressed between 16 PCa and 8 benign prostatic hyperplasia (BPH) tissues; ddPCR (QX200; Bio-Rad Laboratories, USA) was carried out to quantify the expression of selected genes in urine. The urinary molecular PCa risk score (UMPCaRS) was calculated by using the sum of three upregulated genes as the numerator and the sum of three downregulated genes as the denominator. The diagnostic utility of the UMPCaRS was validated by using a screening set (10 PCa and 10 BPH samples) and a validation set (131 PCa and 105 BPH samples)., Results: Three upregulated genes ( PDLIM5 , GDF-15 , THBS4 ) and three downregulated genes ( UPK1A , SSTR3 , NPFFR2 ) were selected from the microarray and subjected to ddPCR. The UMPCaRS for PCa in the screening and validation sets was significantly higher than that for BPH. For the validation set, the diagnostic accuracy of the UMPCaRS was comparable with that of prostate-specific antigen (PSA). Importantly, in the "PSA gray zone" (3-10 ng/mL), the AUC for the UMPCaRS was 0.843 and that for PSA was 0.628 (p<0.001)., Conclusions: The data demonstrate that the UMPCaRS is useful for discriminating between PCa and BPH in the "PSA gray zone"., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (© The Korean Urological Association, 2020.)

Purpose: This study aimed to evaluate the clinical efficacy of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients using real-world data from Korean patients., Materials and Methods: We retrospectively reviewed the medical records of 199 chemotherapy-naïve patients with mCRPC at 13 tertiary centers in Korea between 2014 and 2017. All patients received enzalutamide daily and 89 patients received concurrent androgen deprivation therapy (ADT)., Results: The median age of the patients was 74 years. Initial results showed that 81.5% of the patients had Gleason score ≥8 and 33.3% of the patients had European Cooperative Oncology Group Performance Status 0. The overall mortality rate was 12%. The median OS was not archieved and 76.7% of patients were alive at 30 months. Median time until PSA progression was 6 months. The overall survival rate at 2 years was significantly higher (84.6% vs. 71.7%, p=0.015) and the duration of PSA progression-free survival was significantly longer (8.0 vs. 4.6 months, p=0.008) in patients receiving concurrent ADT than in those receiving enzalutamide alone. The incidence of adverse events of grade 3 or higher was 1.7%. Multivariate Cox proportional hazard analysis indicated that ADT administered concurrently with enzalutamide significantly improved the overall survival (hazard ratio, 0.346; 95% confidence interval, 0.125-0.958)., Conclusions: Enzalutamide is effective and safe for chemotherapy-naïve patients with mCRPC. Furthermore, the overall survival was significantly higher in patients receiving enzalutamide and concurrent ADT than in patients receiving enzalutamide alone., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (© The Korean Urological Association, 2020.)

Purpose: To analyze trends over a period of 28 years in the clinical, operative, and pathologic characteristics of patients with a renal mass who underwent surgical resection in Korea., Materials and Methods: Consecutive patients (n=6,231) with a renal mass who underwent surgical resection at eight Korean institutions between 1988 and 2015 were reviewed. Patients were assigned to one of three groups according to the date of surgery: group 1, 1988-1999; group 2, 2000-2009; and group 3, 2010-2015., Results: Age at the time of surgery, body mass index, smoking status, incidence of diabetes and hypertension, and the number of incidentally identified renal masses increased significantly over time. The proportion of patients undergoing partial nephrectomy (PN) or minimally invasive surgery (MIS) increased sharply during the last two time periods. From 2010, the rate of robot-assisted nephrectomy rose sharply, occurring in 37.8% of MIS cases. Benign pathology was identified in 1.8% and 5.2% of cases in the middle and last periods, respectively; angiomyolipoma was the most common pathology. In later years, tumors were more often localized, although tumor grade increased. Sub-group analysis of small renal masses ≤4 cm revealed similar trends in operative and pathologic characteristics over time., Conclusions: Between 1988 and 2015, there was a substantial change in the clinical, operative, and histological characteristics of patients who underwent resection of a renal mass in Korea. The most notable changes were stage migration towards localized disease and widespread use of PN and MIS., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

High-grade T1 bladder cancer has a poor prognosis due to a higher incidence of recurrence and progression than other nonmuscle invasive bladder cancer; thus patients with high-grade T1 have to be carefully monitored and managed. If patients are diagnosed with high-grade T1 at initial transurethral resection (TUR), a second TUR is strongly recommended regardless of whether muscle layer is present in the specimen because of the possibility of understating due to incomplete resection. Since high-grade T1 disease shows diverse clinical courses, individual approaches are recommended for treatment. In cases with low risk of progression, cystectomy could represent overtreatment and deteriorate quality of life irreversibly, while, in those with high risk, bacillus Calmette-Guérin (BCG) therapy may worsen survival by delaying definitive therapy. Therefore, a strategy for predicting prognosis based on the risk of progression is needed for managing high-grade T1 disease. Molecular risk classifiers predicting the risk of progression and response to BCG may help identify the optimal management of high-grade T1 disease for each individual.

Purpose: Topoisomerase-II alpha (TopoIIA ), a DNA gyrase isoform that plays an important role in the cell cycle, is present in normal tissues and various human cancers, and can show altered expression in both. The aim of the current study was to examine the value of urinary TopoIIA cell-free DNA as a noninvasive diagnosis of bladder cancer (BC)., Materials and Methods: Two patient cohorts were examined. Cohort 1 (73 BC patients and seven controls) provided bladder tissue samples, whereas cohort 2 (83 BC patients, 54 nonmalignant hematuric patients, and 61 normal controls) provided urine samples. Real-time quantitative polymerase chain reaction was used to measure expression of TopoIIA mRNA in tissues and TopoIIA cell-free DNA in urine samples., Results: The results showed that expression of TopoIIA mRNA in BC tissues was significantly higher than that in noncancer control tissues (p<0.001). The expression of urinary TopoIIA cell-free DNA in BC patients was also significantly higher than that in noncancer patient controls and hematuria patients (p < 0.001 and p < 0.001, respectively). High expression of urinary TopoIIA cell-free DNA was also detected in muscle invasive bladder cancer (MIBC) when compared with nonmuscle invasive bladder cancer (NMIBC) (p=0.002). Receiver operating characteristics (ROC) curve analysis was performed to examine the sensitivity/specificity of urinary TopoIIA cell-free DNA for diagnosing BC, NMIBC, and MIBC. The areas under the ROC curve for BC, NMIBC, and MIBC were 0.741, 0.701, and 0.838, respectively., Conclusions: In summary, the results of this study provide evidence that cell-free TopoIIA DNA may be a potential biomarker for BC.

Purpose: To compare the current management of benign prostatic hyperplasia (BPH) by urologists and nonurologists by use of Korean nationwide health insurance data., Materials and Methods: We obtained patient data from the national health insurance system. New patients diagnosed with BPH in 2009 were divided into two groups depending on whether they were diagnosed by a urologist (U group) or by a nonurologist (NU group)., Results: A total of 390,767 individuals were newly diagnosed with BPH in 2009. Of these, 240,907 patients (61.7%) were in the U group and 149,860 patients (38.3%) were in the NU group. The rate of all initial evaluation tests, except serum creatinine, was significantly lower in the NU group. The initial prescription rate was higher in the U group, whereas the prescription period was longer in the NU group. Regarding the initial drugs prescribed, the use of alpha-blockers was common in both groups. However, the U group was prescribed combination therapy of an alpha-blocker and 5-alpha-reductase inhibitor as the second choice, whereas the NU group received monotherapy with a 5-alpha-reductase inhibitor. During the 1-year follow-up, the incidence of surgery was significantly different between the U group and the NU group., Conclusions: There are distinct differences in the diagnosis and treatment of BPH by urologists and nonurologists in Korea. These differences may have adverse consequences for BPH patients. Urological societies should take a leadership role in the management of BPH and play an educational role for nonurologists as well as urologists.

Purpose: We assessed the impact of transobturator tape (TOT) treatment on overactive bladder (OAB) symptoms with a particular focus on nocturia in patients with mixed urinary incontinence (MUI)., Materials and Methods: In this retrospective cohort study, the medical records of 237 women who underwent TOT surgery for the treatment of MUI were reviewed. Of these, 86 patients (36.4%) had preoperative nocturia. Patients with neurological diseases or sleep disorders that could affect the voiding pattern were excluded. Patients who were being treated with anticholinergics and antidiuretic hormones were also excluded, which left 70 subjects eligible for analysis. Pre- and postoperative evaluations consisted of a physical examination, 3-day frequency-volume chart, and health-related quality of life questionnaires (King's health questionnaire, overactive bladder symptom score, and OAB-questionnaire)., Results: TOT treatment resulted in an overall significant improvement in OAB symptoms including nocturia. Frequency-volume charts revealed that TOT treatment significantly decreased the actual number of nightly voids (ANV) and the nocturnal bladder capacity index (NBCi) in the entire cohort. However, in a subgroup of women with nocturnal polyuria, there was no significant change in ANV or NBCi after the sling operation. Correlation analysis of the whole cohort revealed that the postoperative changes in NBCi correlated positively with postoperative changes in ANV. The nocturia-persisting group was more likely to have nocturnal polyuria and lower preoperative functional bladder capacity compared with the nocturia-improved group (p=0.024 and p=0.023, respectively)., Conclusions: Our results demonstrated that the TOT procedure resulted in an overall significant improvement in OAB symptoms including OAB-related nocturia in patients who presented with MUI.

Purpose: MicroRNAs are small noncoding RNAs and microRNA-214 (miR-214) has been associated with the inhibition of cancer cell growth, migration, and invasion. The aim of this study was to investigate whether cell-free miR-214 isolated from urine could be used as a biomarker for non-muscle-invasive bladder cancer (NMIBC)., Materials and Methods: A total of 138 patients with primary NMIBC and 144 healthy normal controls were enrolled in this study. By use of quantitative polymerase chain reaction (PCR), the urinary levels of cell-free miR-214 were measured and the clinicopathological parameters of patients with NMIBC were compared with those of the controls., Results: The urinary levels of cell-free miR-214 were significantly higher in the NMIBC patients than in the controls (20.08±3.21 vs. 18.96±2.68, p=0.002). However, the urinary levels of cell-free miR-214 were neither graded nor staged for the NMIBC patients (p>0.05, each). When we compared the urinary levels of cell-free miR-214 according to clinical outcomes, patients with recurrence had lower levels of miR-214 than did those with no recurrence (19.24±2.67 vs. 20.41±3.41, p=0.023). By contrast, there were no significant differences in the urinary level of cell-free miR-214 between the NMIBC patients showing progression and those showing no progression (p=0.919). Multivariate Cox regression analysis revealed that urinary levels of cell-free miR-214 were an independent predictor of NMIBC recurrence (hazard ratio, 2.011; 95% confidence interval, 1.027 to 3.937; p=0.041)., Conclusions: Urinary levels of cell-free miR-214 could be an independent prognostic parameter for NMIBC recurrence. Thus, urinary cell-free microRNA-214 might be a useful prognostic marker for NMI BC.

Bladder cancer (BC) is the second most common malignancy of urological organs. However, patients with non-muscle-invasive BC are at high risk of recurrence and progression into muscle-invasive BC, and the prognosis of patients with muscle-invasive BC is limited by the high rate of metastasis. The epithelial-mesenchymal transition (EMT) is characterized by loss of cell-to-cell adhesion and cell polarity and is closely associated with the invasion and metastasis of several cancers. Given the multifocality and high rates of relapse, progression, and metastasis of BC, the EMT is likely to participate in BC as well. Numerous factors associate with the EMT, and the key regulators of the EMT are E-cadherin, N-cadherin, Twist, Snail, Slug, Zeb-1, Zeb-2, vimentin, and microRNAs. This review focuses on the current concepts regarding the EMT in cancer and the evidence for involvement of the EMT in BC. Several potential EMT targets that may be useful in the treatment of BC are also described.

Purpose: The deleted in bladder cancer 1 (DBC1) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of DBC1 as a prognostic marker in BC., Materials and Methods: The expression of DBC1 was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model., Results: DBC1 expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low DBC1 expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of DBC1 expression in NMIBC (log-rank test, each, p<0.05)., Conclusions: The expression of DBC1 was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that DBC1 expression can be a useful prognostic marker for patients with NMIBC.

Purpose: Epigenetic alterations such as abnormal DNA methylation are associated with many human cancers. Differences in methylation patterns between neoplastic and normal cells can be used to detect cancer. The aim of the present study was to evaluate the effectiveness of detecting Adenomatous polyposis coli (APC) hypermethylation by quantitative pyrosequencing for discriminating between normal and prostate cancer (PCa) cells and for predicting tumor behaviors., Materials and Methods: A total of 218 human prostate tissues obtained from our institute were assessed: 106 specimens of benign prostatic hyperplasia (BPH) and 112 specimens of PCa. The methylation status of APC was analyzed by quantitative pyrosequencing. The association between the APC methylation level and clinicopathological parameters was explored., Results: The level of APC methylation was significantly higher in PCa specimens than in BPH specimens (33.3%±20.7% vs. 1.3%±1.8%, p<0.001). The sensitivity and specificity of APC methylation status in discriminating between PCa and BPH reached 89.3% and 98.1%, respectively. Similar results were obtained after stratification by stage, Gleason score, and prostate-specific antigen level. The APC methylation level correlated positively with Gleason score (p trend=0.016). There was no association between the APC methylation level and the PSA level or staging., Conclusions: Our results demonstrate that APC methylation is associated with PCa and its aggressive tumor features.

Purpose: We evaluated the value of a combined approach of T1-weighted (T1W) imaging, T2-weighted (T2W) imaging, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) for the detection of prostate cancer and extracapsular extension (ECE) in patients with prostate cancer by using pathologic data after radical prostatectomy., Materials and Methods: From April 2009 to December 2011, 126 patients who underwent radical prostatectomy and prostate MRI for prostate cancer were analyzed retrospectively. The MRI findings were compared with the pathologic findings of the radical prostatectomy specimens in each patient. The sensitivity, specificity, and accuracy of the detection of prostate cancer and extracapsular extension were analyzed., Results: The prostate cancer detection rate by use of T1W and T2W imaging, DCE-MRI, and their combination was 65.1%, 69.0%, and 80.2%, respectively (p=0.023). The detection rate using T1W and T2W imaging, DCE-MRI, DWI, and their combination was 57.7%, 65.4%, 67.3%, and 80.8%, respectively (p=0.086). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of combination MRI (T1W, T2W, and DCE-MRI) for ECE were 46.4%, 91.4%, 83.9%, and 68.1%, respectively. The sensitivity of combination MRI (T1W, T2W, and DCE-MRI) for ECE tended to increase as the prostate-specific antigen level rose (p=0.010). The sensitivity, specificity, PPV, and NPV of combination MRI (T1W, T2W, DCE-MRI, and DWI) for ECE were 65.0%, 87.5%, 76.5%, and 80.0%, respectively., Conclusions: A combined approach of T1W, T2W, and DCE-MRI with DWI demonstrated an accurate detection rate of prostate cancer. Also, combination approaches showed a high specificity for predicting ECE, although sensitivity was relatively lower. Therefore, these methods are reliable for predicting prostate cancer. However, a new protocol is necessary to enhance the sensitivity for predicting ECE.

A 31-year-old man was referred for further management of a urethral stricture. He was a victim of a traffic accident and his urethral injury was associated with a pelvic bone fracture. He had previously undergone a suprapubic cystostomy only owing to his unstable general condition at another hospital. After 3 months of urethral injury, direct urethral anastomosis was attempted, but the surgery failed. An additional 4 failed internal urethrotomies were performed before the patient visited Chungbuk National University Hospital. Preoperative images revealed complete posterior urethral disruption, and the defect length was 4 cm. We performed a buccal mucosa tubal graft without anastomosis of the proximal urethra for a long segment posterior urethral defect. The Foley catheter was removed 3 weeks after the operation and the patient was able to void successfully. After 8 months, he had normal voiding function without urinary incontinence.

Purpose: To validate whether FAM70B, which was found in our micro-array profiling as a prognostic marker for cancer survival, could accurately predict prognosis in patients with muscle-invasive bladder cancer (MIBC)., Materials and Methods: A total of 124 patients with MIBC were enrolled in this study. The FAM70B expression level was analyzed by real-time polymerase chain reaction by using RNA from tumor tissues. The prognostic effect of FAM70B was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model., Results: Kaplan-Meier estimates showed a significant difference in progression-free survival (log-rank test, p=0.011) and cancer-specific survival (log-rank test, p=0.017) according to FAM70B gene expression level. By multivariate Cox regression analysis, high FAM70B expression was predictive of cancer progression (hazard ratio [HR], 2.115, p=0.013) and cancer-specific death (HR, 1.925; p=0.033). In the subgroup analysis, high expression of FAM70B was associated with poor cancer-specific survival, progression-free survival, and overall survival in the patients who underwent cystectomy (log-rank test, p=0.013, p=0.036, p=0.005, respectively). In the chemotherapy group, FAM70B expression was associated with cancer-specific survival and progression-free survival (log-rank test, p=0.013, p=0.042, respectively). Moreover, high FAM70B expression was associated with shorter cancer-specific survival in localized or locally advanced tumor stages (log-rank test, p=0.016)., Conclusions: We confirmed the significance of FAM70B as a prognostic marker in a validation cohort. Therefore, we propose that the FAM70B gene could be used to more precisely predict cancer progression and cancer-specific death in patients with MIBC.

A 69-year-old man with castration-resistant prostate cancer (CRPC) received docetaxel and a corticosteroid. After the third cycle of docetaxel administration, he presented with dyspnea, cough, sputum, and fever of 39.2℃. The chest X-ray and chest computed tomography (CT) revealed a diffuse reticulonodular shadow in both lungs, which suggested interstitial pneumonitis. Initially, we used empiric broad-spectrum antibiotics and high-dose corticosteroids. However, his condition progressively became worse and he was transferred to the intensive care unit, intubated, and placed on mechanical ventilation. He died 4 days after hospital admission. Here we report this case of fatal interstitial pneumonitis after treatment with docetaxel for CRPC. We briefly consider docetaxel-induced pneumonitis to make physicians aware of the possibility of pulmonary toxicity so that appropriate treatment can be begun as soon as possible.

Purpose: DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumor initiation and progression. Differences in methylation patterns between neoplastic and normal cells can be used to detect the presence of cancer. The aim of the present study was to evaluate the usefulness of glutathione-S-transferase-Pi (GSTP1) hypermethylation in discriminating between normal and prostate cancer (PCa) cells and in predicting tumor characteristics by use of quantitative pyrosequencing analysis., Materials and Methods: A total of 100 human prostate tissues obtained from our institute were used in this study: 45 for benign prostatic hyperplasia (BPH) and 55 for PCa. The methylation level of GSTP1 was examined by a quantitative pyrosequencing analysis. The associations between GSTP1 methylation level and clinico-pathological parameter were also compared., Results: The level of GSTP1 methylation was significantly higher in PCa samples than in BPH samples (56.7±32.7% vs. 1.6±2.2%, p<0.001). The sensitivity and specificity of GSTP1 methylation status in discriminating between PCa and BPH reached 85.5% and 100%, respectively. Even after stratification by stage, Gleason score, and prostate-specific antigen (PSA) level, similar results were obtained. A positive correlation between GSTP1 methylation level and serum PSA level was observed (r=0.303, p=0.002). There were no associations between GSTP1 methylation level and age, Gleason score, and staging., Conclusions: Our study demonstrates that GSTP1 methylation is associated with the presence of PCa and PSA levels. This methylation marker is a potentially useful indicator for the detection and monitoring of PCa.

Purpose: The aim of this study was to evaluate the outcome of ureter stones with expectant management and the clinical factors associated with stone passage in Koreans., Materials and Methods: We reviewed the charts of patients who visited the emergency room or urological office of our institution with acute renal colic between 2001 and 2008. A total of 656 ureter stone formers were enrolled in this study who had decided to be treated by expectant management. Clinical data such as gender, age, size and location of the stone, body mass index, and previous stone history were analyzed to find the factors related to spontaneous passage of ureter stones., Results: Of the 656 ureter stones, 566 stones (86.3%) were spontaneously expelled. Mean duration of follow-up was 17.5 days (range, 1 to 100 days). Mean time to stone passage was 6.8 days for stones less than 2 mm in size, 12.6 days for stones 2 to 4 mm, 14.8 days for stones 4 to 6 mm, and 21.8 days for stones 6 to 8 mm (p<0.001). The cumulative spontaneous passage rate was 55.3% in 7 days, 73.7% in 14 days, 88.5% in 28 days, and 97.7% in 60 days after the first attack. A total of 90 patients (13.7%) required interventions because of symptom relapse or renal deterioration that was related to the location and size of the stone (each, p<0.001). The more proximal the location and the larger the stone was than 6 mm, the less the chance of spontaneous passage (each, p<0.001)., Conclusions: Size and location of ureter stones are the most important factors for predicting the spontaneous passage of the stone. If a patient has a distal ureter stone of less than 6 mm in size, it is acceptable for the urologist to observe for spontaneous passage for 2 months.

Urachal adenocarcinomas are very rare and about one third of these neoplasms arise in urachal remnants. To demonstrate the origin of the urachal adenocarcinoma is not easy, but it is very important for managing patient care. We report on a 35-year-old man who complained of a palpable mass in the periumbilical area. The mass was incidentally identified 10 days earlier. Computed tomography revealed a well-defined enhancing mass with internal calcification and septation abutting on the dome of the urinary bladder. The clinical diagnosis was urachal cancer, which seemed to invade the urinary bladder. Thus, we performed mass excision and partial resection of the bladder. Histopathologically, the mass was diagnosed as mucinous cystadenocarcinoma originating from urachal remnants that showed an unusual expression of alpha-methylacyl-coenzyme A racemase (AMACR). To our knowledge, this report is the first case of AMACR-expressing urachal adenocarcinoma arising in the abdominal wall.

A 67-year-old Korean man presented with gross, painless hematuria that had lasted for the previous 2 months. Cystoscopy showed a semispherical tumor approximately 1 cm in diameter that was covered with normal bladder mucosa and extended from the bladder neck to the posterior wall of the bladder. The patient underwent transurethral resection of the tumor. Histological examination and immunohistochemical staining showed a granular cell tumor (GCT). There were no features suggesting a malignant phenotype. On follow-up, the patient has remained free of bladder recurrence. We herein report this case of a GCT of the urinary bladder and review the literature.

Purpose: Recent studies have suggested that renal phosphate leakage and the associated phosphaturia are significant underlying causes of calcium urolithiasis. The aims of this study were to assess whether phosphaturia relates to urinary metabolic abnormalities and recurrent stone formation., Materials and Methods: A database of patient histories and urine chemistries was analyzed for 1,068 consecutive stone formers (SFs) and 106 normal controls. Urine values for phosphaturia that were higher than 95% of the normal control values were defined as indicating hyperphosphaturia, and the effect of phosphaturia on urinary metabolites and stone recurrence was determined. Of these patients, 247 patients (23.1%) who had been followed up for more than 36 months or had a recurrence of stones during follow-up (median, 46.0 months; range, 5-151) were included in the analyses for stone recurrence., Results: Of the SFs, 19.9% (212/1,068) had increased urinary phosphate excretion. SFs with hyperphosphaturia had a greater urinary volume and higher levels of calcium, uric acid, oxalate, and citrate than did SFs with normophosphaturia. A multivariate Cox regression model, stratified by stone episodes, revealed that hyperphosphaturia was an independent predictor of recurrent stone formation in first-time SFs (hazard ratio [HR]: 2.122; 95% confidence interval [CI]: 1.100-4.097; p=0.025). No association was detected between hyperphosphaturia and recurrent stone formation in recurrent SFs. Kaplan-Meier curves showed identical results., Conclusions: This study demonstrates that hyperphosphaturia is closely associated with urinary metabolic abnormalities. Furthermore, hyperphosphaturia is a significant risk factor for stone recurrence in first-time SFs.

Purpose: S100A8 is a member of the S100 protein family containing 2EF-hand calcium-binding motifs. S100 proteins are involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. Altered expression of this protein is associated with various diseases and cancers. The present study aimed to evaluate whether S100A8 has prognostic value for non-muscle-invasive bladder cancer (NMIBC)., Materials and Methods: A total of 103 primary NMIBC samples obtained by transurethral resection were evaluated. mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The results were compared with clinico-pathological parameters. The Kaplan-Meier method was applied to plot the curves for progression-free survival. The multivariate Cox regression model was used to identify the independent prognostic factors for progression., Results: mRNA expression levels of S100A8 were significantly related to the progression of NMIBC. Kaplan-Meier estimates demonstrated significant differences in tumor progression according to the level of S100A8 expression (log-rank test, p<0.001). The multivariate Cox regression model revealed that the S100A8 mRNA expression level (hazard ratio: 12.538; 95% confidence interval: 2.245-70.023, p=0.004) was an independent predictor for disease progression of NMIBC., Conclusions: Expression levels of S100A8 might be a useful prognostic marker for disease progression of NMIBC.

Purpose: Urolithiasis develops more frequently in patients with a family history (FHx). However, little is known about risk factors in stone formers with a FHx. The aim of this study was to examine the clinico-metabolic characteristics of urinary stone formers according to FHx., Materials and Methods: A database of 1,068 stone formers who underwent a complete metabolic evaluation was reviewed. The patients were divided into two groups on the basis of the presence of a FHx. Clinical factors and metabolic parameters were compared between the two groups., Results: There were no significant differences in clinical characteristics, such as gender, age, body mass index, stone episodes, or multiple stones, between the two groups (p>0.05, respectively). Compared with stone formers without a FHx, however, serum calcium concentrations were more elevated in stone formers with a FHx. Also, the urinary excretion of calcium was higher in stone formers with a FHx than in those without a FHx. Other urinary metabolites showed no significant differences between the two groups (p>0.05, respectively)., Conclusions: Our study revealed that stone formers with a FHx had increased urinary calcium excretion as well as elevated concentrations of serum calcium. This finding suggests that urolithiasis in stone formers with a FHx may be associated with calcium metabolic abnormalities.