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Background: Delayed-release dimethyl fumarate (DMF), indicated for the treatment of patients with relapsing-remitting multiple sclerosis (MS), is a disease-modifying therapy with potential immunomodulatory and neuroprotective effects. In clinical trials, DMF was associated with reduced white blood cell and absolute lymphocyte counts. Current US prescribing information recommends obtaining a complete blood count, including absolute lymphocyte count (ALC), before initiating and during DMF treatment., Methods: We conducted an integrated analysis of phase 2b/3/long-term extension studies of DMF in MS (N = 2,470) to characterize ALC profiles., Results: Mean ALCs decreased by 30% during the first year and then plateaued, remaining above the lower limit of normal (LLN). Among patients treated ≥6 months (N = 2,099), 2.2% experienced ALCs <500 mm 3 persisting ≥6 months. ALCs remained ≥LLN in 84% and 76% of patients during the first 6 and 12 months, respectively; of these, 0.1% and 0%, respectively, developed ALCs <500 mm 3 persisting ≥6 months at any time. Evidence of ALC improvement following DMF discontinuation was observed. DMF efficacy was not substantially different in patients with and without lymphopenia., Conclusion: Lymphocyte monitoring provides effective means for early identification of patients at risk for developing severe, prolonged lymphopenia.

Bladder cancer is a significant clinical and economic problem. Despite intravesical chemotherapy and immunotherapy, up to 80% of patients with non-muscle-invasive bladder cancer develop recurrent tumors, of which 20% to 30% evolve into more aggressive, potentially lethal tumors. Recently, bladder cancer cells are considered to be mediators of resistance to current therapies and therefore represent strong candidates as biologic targets. No effective chemotherapy has yet been developed for advanced bladder cancer. It is desirable that a drug can be delivered directly and specifically to bladder cancer cells. Stem cells have selective migration ability toward cancer cells, and therapeutic genes can be easily transduced into stem cells. In suicide gene therapy for cancer, stem cells carry a gene encoding a carboxylesterase (CE) enzyme that transforms an inert CPT-11 prodrug into a toxic SN-38 product, a topoisomerase 1 inhibitor. In immunodeficient mice, systemically transplanted HB1.F3.CE stem cells migrated toward the tumor implanted by the TCCSUP bladder cancer cell line, and, in combination with CPT-11, the volume of tumors was significantly reduced. These findings may contribute to the development of a new selective chemotherapeutic strategy against bladder cancer. Mol Cancer Ther; 15(6); 1201-7. ©2016 AACR., (©2016 American Association for Cancer Research.)

This study aimed to investigate the overall cumulative exposure-response and the lag response relationships between daily temperature and urolithiasis presentation in Seoul. Using a time-series design and distributing lag nonlinear methods, we estimated the relative risk (RR) of urolithiasis presentation associated with mean daily temperature, including the cumulative RR for a 20 days period, and RR for individual daily lag through 20 days. We analyzed data from 14,518 patients of 4 hospitals emergency department who sought medical evaluation or treatment of urolithiasis from 2005-2013 in Seoul. RR was estimated according to sex and age. Associations between mean daily temperature and urolithiasis presentation were not monotonic. Furthermore, there was variation in the exposure-response curve shapes and the strength of association at different temperatures, although in most cases RRs increased for temperatures above the 13°C reference value. The RRs for urolothiasis at 29°C vs. 13°C were 2.54 in all patients (95% confidence interval [CI]: 1.67-3.87), 2.59 in male (95% CI, 1.56-4.32), 2.42 in female (95% CI, 1.15-5.07), 3.83 in male less than 40 years old (95% CI, 1.78-8.26), and 2.47 in male between 40 and 60 years old (95% CI, 1.15-5.34). Consistent trends of increasing RR of urolithiasis presentation were observed within 5 days of high temperatures across all groups. Urolithiasis presentation increased with high temperature with higher daily mean temperatures, with the strongest associations estimated for lags of only a few days, in Seoul, a metropolitan city in Korea.

Cancer cells, and in particular those found circulating in blood, can have widely varying phenotypes and molecular profiles despite a common origin. New methods are needed that can deconvolute the heterogeneity of cancer cells and sort small numbers of cells to aid in the characterization of cancer cell subpopulations. Here, we describe a new molecular approach to capturing cancer cells that isolates subpopulations using two-dimensional sorting. Using aptamer-mediated capture and antisense-triggered release, the new strategy sorts cells according to levels of two different markers and thereby separates them into their corresponding subpopulations. Using a phenotypic assay, we demonstrate that the subpopulations isolated have markedly different properties. This system provides an important new tool for identifying circulating tumor cell subtypes.

Purpose: Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression., Materials and Methods: We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013., Results: Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax., Conclusion: This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha-blockers as an initial treatment strategy for men with lower urinary tract symptoms.

Purpose: To compare radiation dose and image quality in regular, low, and ultralow-dose CT protocols, and to evaluate diagnostic performance of low-dose CT for urolithiasis., Materials and Methods: Sixty-five patients with suspected urolithiasis underwent three different scans under the regular, low, and ultralow-dose protocols. The regular dose scans were reconstructed using filtered back projection and the low-dose scans were reconstructed using a statistical iterative reconstruction. The ultralow-dose scans were reconstructed using both techniques in addition to a knowledge-based IR. Effective radiation doses were compared. Objective image noise was assessed by measuring standard deviation of HU and subjective image assessment was performed with a 3- or 5-point scale. Diagnostic performance of the low-dose image was evaluated, using the regular dose image as a standard reference and the interobserver agreement between two reviewers with different levels of experience was calculated., Results: The effective radiation dose was significantly different in each protocol (p < 0.001) and estimated dose reduction of the low-dose and ultralow-dose protocols was 76.4% and 89.8%, respectively. The knowledge-based iterative reconstruction algorithm showed poorer subjective image quality than the regular and low-dose protocols, but it also had the least objective image noise. Overall, the low-dose image set showed a greater than 84% concordance rate and 100% in ureter stones larger than 3 mm. Interobserver agreement was substantial (kappa value = 0.61)., Conclusions: The knowledge-based IR can provide a better quality image while reducing radiation exposure under the same protocol. Furthermore, the diagnostic performance of the low-dose CT protocol is comparable to the regular dose scan.

We aimed to determine normal reference ranges for prostate volume (PV) and annual PV change rate in a Korean nationwide screening population. Data from men who underwent a routine health check-up were collected from 13 university hospitals. The cohort comprised men aged ≥40 yr who had undergone 2 or more serial transrectal ultrasonographies. Men with initial PV>100 mL; serum PSA level>10 ng/mL; PV reduction>20% compared with initial PV, or who had history of prostate cancer or prostate surgery, were excluded. Linear regression and mixed effects regression analyses were used to predict mean PV and longitudinal change in PV over time. A total of 2,967 men formed the study cohort. Age, body mass index (BMI), and serum prostate-specific antigen (PSA) level were found to be significant predictors of PV. A predicted PV table, with a 95% confidence interval (CIs), was developed after adjusting for these 3 variables. Annual PV change rate was 0.51 mL/year (95% CI, 0.47-0.55). Annual PV change rate according to age was 0.68 mL/year, 0.84 mL/year, 1.09 mL/year, and 0.50 mL/year for subjects in their 40s, 50s, 60s, and ≥70 yr, respectively. Predicted annual PV change rate differed depending on age, BMI, serum PSA level and baseline PV. From a nationwide screening database, we established age-, PSA-, and BMI-specific reference ranges for PV and annual PV change rate in Korean men. Our newly established reference ranges for PV and annual PV change rate will be valuable in interpreting PV data in Korean men.

Aim: We determined to investigate the effect of plasma hemodilution on tumor marker concentration in obese women., Methods: We collected the data for tumor markers (cancer-associated antigen 125 [CA125], carbohydrate antigen 19-9 [CA19-9], carcinoembryonic antigen [CEA] and α-fetoprotein) from 6917 healthy women who visited the health promotion center at the Chung-Ang University Hospital from 2003 to 2011. We used multivariate linear regression analysis and χ(2) -test for linear-by-linear association adjusting for age, alanine aminotransferase and creatinine to determine the association between the serum tumor marker concentrations, plasma volume, tumor marker mass, and body mass index (BMI)., Results: Higher BMI was significantly associated with higher plasma volume (P < 0.001 for trend). The lower concentrations of CA125 and CA19-9 were significantly associated with increasing BMI (P < 0.001). Serum concentration and mass of CEA and α-fetoprotein were increased with higher BMI in obese women (P < 0.001). CEA in women had the opposite result to that in men due to visceral fat in women., Conclusion: This study shows that we should consider the hemodilution effect in Asian obese women when interpreting serum tumor marker concentration in cancer screening., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Sonographic findings of a prescrotal superficial angiomyxoma have never been reported in the English literature. Here, we describe a case of left prescrotal superficial angiomyxoma, which was depicted on ultrasonography as a well-circumscribed, heterogeneously, and mildly echogenic, unilocular complex, posterior acoustic-enhanced, and dermally attached subcutaneous mass without increased vascular flow.

Objective: To confirm the role of cathelicidin (LL-37) in the internalization of bacille Calmette-Guérin (BCG) into bladder cancer cells., Methods: Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction analysis evaluated the changes in protein and messenger ribonucleic acid (RNA) expression with BCG incubation after LL-37 pretreatment in 5637 and T24 human bladder cancer cells. The internalization rate was evaluated by a double immunofluorescence assay, and confocal microscopy confirmed the function of LL-37 in BCG internalization. We also investigated the difference in internalization rates and cell viability between LL-37, anti-LL-37 antibody, and LL-37 plus anti-LL-37 antibody., Results: The levels of LL-37 increased after BCG exposure in bladder cancer cells in dose- and time-dependent manners. Increasing LL-37 levels using recombinant LL-37 protein further dose dependently decreased BCG internalization in both cell lines. The internalization rates of BCG after LL-37 instillation were lower compared with the controls, and the internalization rate of BCG after anti-LL-37 antibody instillation was significantly higher compared with the controls in both cell lines (P <.05). Viability of LL-37 plus BCG group was higher compared with the BCG-alone group. The anti-LL-37 antibody plus BCG group had decreased cell viability compared with the BCG-alone group in both cell lines., Conclusion: Bladder cancer cells produce cathelicidin when infected with BCG and upregulate cathelicidin to defend against BCG by inhibiting its internalization. Blocking the action of cathelicidin may increase the internalization and effectiveness of BCG in reducing bladder cancer cell proliferation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We investigated whether bacillus Calmette-Guérin (BCG)-induced secretion of murine β-defensin-2 (mBD2) and determined whether mBD2 regulated BCG effects in the normal mouse bladder., Materials and Methods: A total of 140 C57BL/6 female mice were divided into 28 groups, and the experiment was performed over 3 steps. In the first step (20 groups), mice bladders were stimulated with different doses of BCG (multiplicity of infection [MOI] 0, 1, 10, 30, and 100) and histological analysis was conducted in bladder specimens isolated at different times (0, 4, 8, and 24h after instillation) to determine optimal dose and time point of BCG internalization and urine mBD2 and cytokine concentration. In the second step (4 groups), BCG internalization and urine cytokine levels were measured after pretreatment of different recombinant mBD2 (rmBD2) (0, 1, 2.5, and 5 ng/ml) at optimal dose and time point. In the third step (4 groups), BCG internalization and urine cytokine levels were compared between pretreatment conditions (control, rmBD2, anti-mBD2 Ab, and rmBD2+anti-mBD2 Ab). Urine was collected for estimating mBD2 levels and a multiplex analysis for 9 cytokines. Real-time polymerase chain reaction assay was used for estimating the relative BCG cell number in mice bladder tissue., Results: Bladder edema was induced by BCG (MOI 30 and 100), which progressed to an inflammatory infiltrate composed primarily of neutrophils and increased mBD2 secretion at 4 hours after instillation. Relative BCG cell number and urinary cytokine levels (interferon-γ and interleukins [IL]-2, -4, -6, and -10) response pattern was characterized by a peak at 4 hours after instillation followed by rapid decline. The levels of interferon-γ, and IL-1β, -2, -4, -6, and -10 and relative BCG cell numbers decreased in a dose-dependent manner according to pretreatment with rmBD2 protein, and the responses were potentiated in the anti-mBD2 pretreatment group at 4 hours after BCG (MOI 30) instillation., Conclusion: The present results suggest that the mouse urothelium produces mBD2 in response to intravesicular BCG as a defense mechanism against BCG, and blocking mBD2 by an anti-mBD2 antibody increased the effectiveness of BCG., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We investigated how the dual inhibition of the molecular mechanism of the mammalian target of the rapamycin (mTOR) downstreams, P70S6 kinase (P70S6K) and eukaryotic initiation factor 4E (eIF4E), can lead to a suppression of the proliferation and progression of urothelial carcinoma (UC) in an orthotopic mouse non-muscle invasive bladder tumor (NMIBT) model. A KU-7-luc cell intravesically instilled orthotopic mouse NMIBC model was monitored using bioluminescence imaging (BLI) in vivo by interfering with different molecular components using rapamycin and siRNA technology. We then analyzed the effects on molecular activation status, cell growth, proliferation, and progression. A high concentration of rapamycin (10 µM) blocked both P70S6K and elF4E phosphorylation and inhibited cell proliferation in the KU-7-luc cells. It also reduced cell viability and proliferation more than the transfection of siRNA against p70S6K or elF4E. The groups with dual p70S6K and elF4E siRNA, and rapamycin reduced tumor volume and lamina propria invasion more than the groups with p70S6K or elF4E siRNA instillation, although all groups reduced photon density compared to the control. These findings suggest that both the mTOR pathway downstream of eIF4E and p70S6K can be successfully inhibited by high dose rapamycin only, and p70S6K and Elf4E dual inhibition is essential to control bladder tumor growth and progression.

Objective: To evaluate the efficacy of low-dose nonenhanced computed tomography (LDCT) with iterative reconstruction (IR) technique for urologists to detect urolithiasis by comparing diagnostic performance and interobserver agreement between the urologist and the uroradiologist., Patients and Methods: We evaluated the 116 patients with urinary stones (n = 197) using both conventional-dose nonenhanced computed tomography (CT) using filtered back projection (CDCT-FBP) and LDCT-IR. Scans were interpreted for stone characteristics, objective image noise, and subjective image assessment. Diagnostic performance and interobserver agreement of LDCT-IR were assessed between 1 urologist and 1 radiologist., Results: There were no significant differences in all stones. The average effective dose (mSV) in the all size groups was 5.92 (CDCT-FBP) and 1.39 (LDCT-IR), respectively (P <.001). The average effective dose reduction rate was 76.6%, allowing minimal additional radiation exposure from simultaneous CT. Objective image noise was higher in LDCT-IR (20.0-26.2; P <.01), but there was no significant difference in the Hounsfield unit between both CT protocols (52.3 and 56.7; P = .103). There were no cases of any unacceptable images in subjective image assessment. The sensitivity and specificity of LDCT-IR were 99.1%-100.0% with a diagnostic accuracy of 99.1%-100% for stones ≥3 mm. Diagnostic performance was similar between the urologist and the radiologist. Interobserver agreement of LDCT-IR between the 2 reviewers was high with kappa values (0.901-1.000)., Conclusion: LDCT-IR provided an excellent diagnostic performance and interobserver agreement between the urologist and the uroradiologist, reducing radiation exposure significantly; in real settings, the urologist should consider replacing LDCT-IR as the standard examination for detecting urolithiasis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We compared the clinical utility of nonenhanced computed tomography (NECT) and intravenous urography (IVU) in patients with classic symptoms of renal colic without evidence of a urine infection. This was a retrospective analysis of IVU and NECT performed in adult patients with suspected renal colic at an emergency department between January 2005 and December 2013. The records of all patients in NECT and IVU groups were reviewed, and the patients were categorized according to the cause of their symptoms. A total of 2218 patients were enrolled. Of these patients, 1525 (68.8%) underwent IVU and 693 (31.2%) underwent NECT. The patients in NECT group were older (45.48 ± 14.96 versus 42.37 ± 13.68 years, p < 0.001), had less gross hematuria (7.6 versus 2.9%, p < 0.001), and were admitted more often (18.6 versus 12.0%, p < 0.001) than the patients in IVU group. Urinary stones were detected in 1413 (63.7%) patients. NECT had a higher detection rate of urolithiasis than IVP (74.0 versus 59.0%, p < 0.001). No significant difference was observed in the incidence of urinary stones greater than 4mm between groups from the radiologic findings (p = 0.79) or the full medical record review (p = 0.87).

Imidazolium salts, [RS(O)-CH2 (C3 H3 N2 )Mes]Cl (R=Me (L1a), Ph (L1b)); Mes=mesityl), make convenient carbene precursors. Palladation of L1a affords the monodentate dinuclear complex, [(PdCl2 {MeS(O)CH2 (C3 H2 N2 )Mes})2 ] (2a), which is converted into trans-[PdCl2 (NHC)2] (trans-4a; N-heterocyclic carbene) with two rotamers in anti and syn configurations. Complex trans-4a can isomerize into cis-4a(anti) at reflux in acetonitrile. Abstraction of chlorides from 4a or 4b leads to the formation of a new dication: trans-[Pd{RS(O)CH2(C3H2N2)Mes}2](PF6)2 (R=Me (5a), Ph (5b)). The X-ray structure of 5a provides evidence that the two bidentate SO-NHC ligands at palladium(II) are in square-planar geometry. Two sulfoxides are sulfur- and oxygen-bound, and constitute five- and six-membered chelate rings with the metal center, respectively. In acetonitrile, complexes 5a or 5b spontaneously transform into cis-[Pd(NHC)2(NCMe)2](PF6)2. Similar studies of thioether-NHCs have also been examined for comparison. The results indicate that sulfoxides are more labile than thioethers., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: To characterize voiding symptoms during the peri- and post-menopausal periods and to investigate related hormonal changes., Methods: We enrolled a total of 55 patients between February 10, 2013, and August 15, 2013, to participate in this cross-sectional study. To characterize patients' voiding symptoms, we administered voiding questionnaires, including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and Sandvik Severity Index. Measured hormones included E2, FSH, TSH, prolactin, progesterone, and testosterone., Results: In the univariate analysis, there were significant intergroup differences for all of the hormones except progesterone. Among the voiding symptoms, straining (IPSS question 1), frequency (IPSS question 2), and SUI were significantly different between the two groups (p=0.039. 0.010, and 0.017, respectively). In the multivariate analysis, frequency (IPSS question 2) and SUI were significantly different between the two groups (p=0.020 and 0.011, respectively). Among the hormones, only testosterone was marginally different between the two groups (p=0.059)., Conclusions: During the transition to menopause, voiding symptoms, such as frequency, can potentially worsen in the peri-menopausal period, and SUI is more prevalent in the post-menopausal period. Additionally, testosterone may have a role in voiding changes that occur during the menopausal transition., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Complications after prostate biopsy have increased and various causes have been reported. Growing evidence of increasing quinolone resistance is of particular concern. In the current retrospective study, we evaluated the incidence of infectious complications after prostate biopsy and identified the risk factors., Materials and Methods: The study population included 1,195 patients who underwent a prostate biopsy between January 2007 and December 2012 at Chung-Ang University Hospital. Cases of febrile UTI that occurred within 7 days were investigated. Clinical information included age, prostate-specific antigen, prostate volume, hypertension, diabetes, body mass index, and biopsy done in the quinolone-resistance era. Patients received quinolone (250 mg intravenously) before and after the procedure, and quinolone (250 mg) was orally administered twice daily for 3 days. We used univariate and multivariate analysis to investigate the predictive factors for febrile UTI., Results: Febrile UTI developed in 39 cases (3.1%). Core numbers increased from 2007 (8 cores) to 2012 (12 cores) and quinolone-resistant bacteria began to appear in 2010 (quinolone-resistance era). In the univariate analysis, core number≥12 (p=0.024), body mass index (BMI)>25 kg/m(2) (p=0.004), and biopsy done in the quinolone-resistance era (p=0.014) were significant factors. However, in the multivariate analysis adjusted for core number, the results were not significant, with the exception of BMI>25 kg/m(2) (p=0.011) and biopsy during the quinolone-resistance era (p=0.035), which were significantly associated with febrile UTI., Conclusions: Quinolone resistance is the main cause of postbiopsy infections in our center. We suggest that further evaluation is required to validate similar trends. Novel strategies to find alternative prophylactic agents are also necessary.

Purpose: This study aimed to confirm the utility of the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) scoring systems and to determine which model is preferred as a prognostic model in Korean patients with non-muscle-invasive bladder cancer., Materials and Methods: Between 1985 and 2011, 531 patients who were treated by transurethral resection of bladder cancer were retrospectively analyzed by use of the EORTC and CUETO models. Statistically, we performed Kaplan-Meier survival analysis; calculated Harrell's concordance index, receiver operating characteristic (ROC) curve, and cutoff values; and performed univariate and multivariate Cox proportional hazards regression analyses., Results: For risk of recurrence, with the use of the EORTC model, all groups had statistically significant differences except between the group with a score of 0 and the group with a score of 1-4. With the use of the CUETO model, all groups differed significantly. For risk of progression, with the use of the EORTC model, significant differences were observed between all groups except between the group with a score of 2-6 and the group with a score of 7-13. With the use of the CUETO model, a significant difference was observed between the group with a score of 0 and the other groups. The concordance index of the EORTC and CUETO models was 0.759 and 0.836 for recurrence and 0.704 and 0.745 for progression, respectively. The area under the ROC curve for the EORTC and CUETO models was 0.832 and 0.894 for recurrence and 0.722 and 0.724 for progression, respectively., Conclusions: Both scoring systems, especially the CUETO model, showed value in predicting recurrence and progression in Korean patients, which will help in individualizing treatment and follow-up schedules.

Purpose: To evaluate the efficacy of low-dose computed tomography (LDCT) for detecting urinary stones with the use of an iterative reconstruction technique for reducing radiation dose and image noise., Materials and Methods: A total of 101 stones from 69 patients who underwent both conventional nonenhanced computed tomography (CCT) and LDCT were analyzed. Interpretations were made of the two scans according to stone characteristics (size, volume, location, Hounsfield unit [HU], and skin-to-stone distance [SSD]) and radiation dose by dose-length product (DLP), effective dose (ED), and image noise. Diagnostic performance for detecting urinary stones was assessed by statistical evaluation., Results: No statistical differences were found in stone characteristics between the two scans. The average DLP and ED were 384.60 ± 132.15 mGy and 5.77 ± 1.98 mSv in CCT and 90.08 ± 31.80 mGy and 1.34 ± 0.48 mSv in LDCT, respectively. The dose reduction rate of LDCT was nearly 77% for both DLP and ED (p<0.01). The mean objective noise (standard deviation) from three different areas was 23.0 ± 2.5 in CCT and 29.2 ± 3.1 in LDCT with a significant difference (p<0.05); the slight increase was 21.2%. For stones located throughout the kidney and ureter, the sensitivity and specificity of LDCT remained 96.0% and 100%, with positive and negative predictive values of 100% and 96.2%, respectively., Conclusions: LDCT showed significant radiation reduction while maintaining high image quality. It is an attractive option in the diagnosis of urinary stones.

Renal oncocytosis is a very rare cause of multiple renal masses. Imaging features of renal oncocytosis and combined tumors have rarely been reported. Here, we describe a case of unilateral left renal oncocytosis and a combined hybrid tumor between chromophobe renal cell carcinoma and oncocytoma, which were depicted on CT and MR imaging as multiple enhancing solid masses with one dominant mass. Additionally, we reviewed the literature.

This multicenter study was undertaken to determine the efficacy of antibiotic prophylaxis and identify the risk factors for infectious complications after prostate surgery in Korean patients. A total of 424 patients who underwent surgery of the prostate were reviewed. All patients underwent urinalysis and urine culture preoperatively and postoperatively. Efficacy of antibiotic prophylaxis and risk factors for infectious complications were investigated. Infectious complications were observed in 34.9% of all patients. Factors independently associated with infectious complications were diabetes mellitus (adjusted OR, 1.99; 95% CI, 1.09-3.65, P=0.025) and operation time (adjusted OR, 1.08; 95% CI, 1.03-1.13, P=0.004). Clinicians should be aware of the high risk of infectious complications in patients with diabetes and those who undergo a prolonged operation time. Neither the type nor duration of prophylactic antibiotics resulted in differences in infectious complications.

We investigated whether inhibiting phosphorylated p70S6K (p-p70S6K) suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma (LG-URCa) in vitroand whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray (TMA) for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group (P < 0.05; hazard ratio (HR), 2.415) and the high p-p70S6K staining group (P < 0.05; HR, 2.249) were independent factors for predicting recurrence. Rapamycin inhibited RT4 and 253J cell proliferation in a dose-dependent manner (r = -0.850, P< 0.001 in RT4 cells; r = -0.835, P< 0.001 in 253J cells). RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively (P < 0.05). Transfection of p70S6K siRNA resulted in inhibitory effects on cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder.

Objectives: We investigated whether multiparametric magnetic resonance imaging is appropriate to localize prostate cancer foci in Koreans., Methods: A total of 141 prostate cancer foci in 115 prostate specimens from patients who had undergone radical prostatectomy with preoperative 3 Tesla multiparametric magnetic resonance imaging including T2-weighted imaging, diffusion weighted imaging and magnetic resonance spectroscopy. Differences in the histopathological findings between detected and undetected prostate cancer foci on multiparametric magnetic resonance imaging were investigated., Results: The mean tumor size was 1.9 cm, and 31.9%, 48.9%, and 19.9% of the patients had Gleason scores of 6, 7, or ≥8, respectively. The detection rates of prostate cancer foci were 54.6%, 57.4%, 55.3%, and 45.4% on multiparametric magnetic resonance imaging, T2-weighted imaging, diffusion weighted imaging, and magnetic resonance spectroscopy, respectively. On multivariate analysis, tumor size ≥1.5 cm (odds ratio 3.1; 95% confidence interval 1.31–7.49), Gleason score >7 (4 + 3; odds ratio 2.9; 95% confidence interval 1.05–8.05), and a malignant epithelium/stroma ratio of ≥60% (odds ratio 2.9; 95% confidence interval 1.14–7.20) were significant independent predictors of prostate cancer foci detection on multiparametric magnetic resonance imaging and diffusion weighted imaging. In a multivariate linear model analysis, the apparent diffusion coefficient value was inversely associated with maximum tumor diameter (β = −0.242, P < 0.05), Gleason score (β = −0.234, P < 0.05)and high malignant epithelium/stroma ratio (β = −0.229, P < 0.05)., Conclusions: Distinct histological differences between prostate cancer foci that were detected and missed by multiparametric magnetic resonance imaging can be identified. Despite limitations, multiparametric magnetic resonance imaging seems useful for determining prostate cancer in Korean patients, particularly with Gleason score >7 and tumor diameter>1.5 cm.

We established an orthotopic non-muscle invasive bladder cancer (NMIBC) mouse model expressing the mammalian target of the rapamycin (mTOR) signaling pathway. After intravesical instillation of KU-7-lucs (day 0), animals were subsequently monitored by bioluminescence imaging (BLI) on days 4, 7, 14, and 21, and performed histopathological examination. We also validated the orthotopic mouse model expressing the mTOR signaling pathway immunohistochemically. In vitro BLI photon density was correlated with KU-7-luc cell number (r (2) = 0.97, P < 0.01) and in vivo BLI photon densities increased steadily with time after intravesical instillation. The tumor take rate was 84.2%, formed initially on day 4 and remained NMIBC up to day 21. T1 photon densities were significantly higher than Ta (P < 0.01), and histological tumor volume was positively correlated with BLI photon density (r (2) = 0.87, P < 0.01). The mTOR signaling pathway-related proteins were expressed in the bladder, and were correlated with the western blot results. Our results suggest successful establishment of an orthotopic mouse NMIBC model expressing the mTOR signaling pathway using KU-7-luc cells. This model is expected to be helpful to evaluate preclinical testing of intravesical therapy based on the mTOR signaling pathway against NMIBC.

As a continuous study we prepared several alkylamine (n = 3-6) and evaluated for the pharmacological activity and mode of action. In the topoisomerase IIα (topo IIα) inhibition test, compound 4 showed strongest inhibitory activity among the compounds at 10 μM. Inhibitory activities of the compounds are in the order of 4 (n = 4) > 1 (n = 3) >> 5 (n = 5) ≈ 6 (n = 6); 8 (n = 4) >> 7 (n = 3) ≈ 9 (n = 5) ≈ 10 (n = 6) where n is the number of carbon in the aliphatic side chain in ring C and compounds 7-10 have additional methoxy group in ring A compared to compounds 1, 4-6. Compound 4 showed efficient cytotoxicities against T47D (IC₅₀: 0.93 ± 0.04 μM) and HCT15 (IC50: 0.78 ± 0.01 μM) cells, which are higher than etoposide. Compound 4 was also an ATP-competitive human topo IIα catalytic inhibitor with partially blocking human topo IIα-catalyzed ATP hydrolysis and intercalating into DNA. Compound 4 induced much less DNA damage than etoposide in HCT15 human colorectal carcinoma cells. Overall, compound 4 can be a potential anticancer agent acting as topo IIα catalytic inhibitor with low DNA damage., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate whether secretion of human β-defensin 2 (HBD-2) is induced by bacillus Calmette-Guérin (BCG) and to determine whether HBD-2 affects BCG internalisation in bladder cancer cells., Materials and Methods: Reverse transcription-polymerase chain reaction analysis was used to determine whether HBD-2 mRNA increases after incubation with BCG. HBD-2 proteins in 5637 and T24 human bladder cancer cell lines were assayed by enzyme-linked immunosorbent assay. The internalisation rate was evaluated by double immunofluorescence assay and confocal microscopy to test the optimal dose of HBD-2 for BCG internalisation. We also investigated the difference in internalisation rates and cell viability between recombinant HBD-2 protein, anti-HBD-2 antibody, and HBD-2 plus anti-HBD-2 antibody pretreatments., Results: BCG induced HBD-2 mRNA expression and HBD-2 production dose and time-dependently in bladder cancer cells and affected BCG internalisation. Pretreatment with recombinant HBD-2 protein lowered internalisation of BCG dose-dependently. Moreover, anti-HBD-2 antibody prevented the effect of HBD-2 on BCG internalisation in bladder cancer cells. The internalisation rate of BCG pretreated with anti-HBD-2 antibody was higher than that in the control in 5637 (P < 0.01) and T24 cells (P < 0.05). The BCG internalisation rate in cells pretreated with anti-HBD-2 antibody plus recombinant HBD-2 protein was higher than that in the control in 5637 (P < 0.01) and T24 cells (P < 0.05). Mycobacterium bovis BCG decreased bladder cancer cell viability, and anti-HBD-2 antibody prevented the inhibitory role of HBD-2 on the anti-proliferative effects of M. bovis BCG in bladder cancer cells, Conclusion: Bladder cancer cells produce HBD-2 when they are infected by BCG to defend themselves against BCG internalisation, which plays an important role during the initiation and propagation of the immunotherapeutic response in bladder cancer cells., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To investigate the safety, tolerability, pharmacokinetics, and antiviral activity of BMS-986001 (a nucleoside reverse transcriptase inhibitor) in treatment-experienced, HIV-1-infected subjects not exposed to antiretroviral treatment in the previous 3 months., Methods: Thirty-two HIV-1-infected subjects were randomized (3:1) to receive BMS-986001 or placebo once daily for 10 days in this double-blind, placebo-controlled, dose-escalating monotherapy phase IIa study. There were 4 treatment groups (100, 200, 300, and 600 mg, all once daily) of 8 subjects each (BMS-986001, n = 6/placebo n = 2)., Results: BMS-986001 was generally well tolerated, with no discontinuations due to adverse events and no deaths occurring. Adverse events were experienced by 22 of 24 BMS-986001-treated subjects and did not seem to be dose related. The majority were mild and considered unrelated or unlikely to be related to the study drug. The pharmacokinetics of BMS-986001 were dose proportional. Median decrease in plasma HIV-1 RNA from baseline to day 11 was 0.97, 1.15, 1.28, and 1.15 log10 copies/mL for BMS-986001 at 100, 200, 300, and 600 mg, respectively. Plasma area under the curve correlated with the antiviral activity of BMS-986001, indicating that area under the curves produced by 100-600 mg doses were on the upper end of the exposure-response curve. One subject with a single thymidine analog mutation at baseline responded well to BMS-986001., Conclusions: Administration of BMS-986001 for 10 days resulted in substantial decreases in plasma HIV-1 RNA levels for all dose groups and was generally well tolerated. These data support continued clinical development of BMS-986001 at a dose of 100 mg, once daily or greater., Trial Registration: EUDRACT Number 2008-004810-29.

Purpose: The aim of this study was to evaluate the effectiveness of simultaneous flexible ureteroscopic removal of stones (URS) for ureteral and ipsilateral renal stones and to analyze the predictive factors for renal stone-free status., Materials and Methods: We retrospectively reviewed the records of patients who underwent simultaneous flexible URS of ureteral and ipsilateral renal stones from January 2010 to May 2012. All operations used a flexible ureteroscope. We identified 74 cases of retrograde intrarenal surgery and 74 ureteral stones (74 patients). Stone-free status was respectively defined as no visible stones and clinically insignificant residual stones <3 mm on a postoperative image study. Predictive factors for stone-free status were evaluated., Results: The immediate postoperative renal stone-free rate was 70%, which increased to 83% at 1 month after surgery. The immediate postoperative ureteral stone-free rate was 100%. Among all renal stones, 15 (20.3%) were separately located in the renal pelvis, 11 (14.8%) in the upper calyx, 15 (20.3%) in the mid calyx, and 33 (44.6%) in the lower calyx. The mean cumulative stone burden was 92.22±105.75 mm(2). In a multivariate analysis, cumulative stone burden <100 mm(2) was a significant predictive factor for postoperative renal stone-free status after 1 month (p<0.01)., Conclusions: Flexible URS can be considered simultaneously for both ureteral and renal stones in selected patients. Flexible URS is a favorable option that promises high stone-free status without significant complications for patients with a stone burden <100 mm(2).

Persistent and disabling pain is the hallmark of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, disease severity (as measured by objective indexes such as those that use radiography or serology) is only marginally related to patients' reports of pain severity, and pain-related presentation can differ widely among individuals with CP/CPPS. Increasing evidence in support of the biopsychosocial model of pain suggests that cognitive and emotional processes are crucial contributors to inter-individual differences in the perception and impact of pain. This review describes the growing body of literature relating depression and catastrophizing to the experience of pain and pain-related sequelae in CP/CPPS. Depression and catastrophizing are consistently associated with the reported severity of pain, sensitivity to pain, physical disability, poor treatment outcomes, and inflammatory disease activity and potentially with early mortality. A variety of pathways, from cognitive to behavioral to neurophysiological, seem to mediate these deleterious effects. Collectively, depression and catastrophizing are critically important variables in understanding the experience of pain in patients with CP/CPPS. Pain, depression, and catastrophizing might all be uniquely important therapeutic targets in the multimodal management of a range of such conditions.

Purpose: The location of acetylcholinesterase-containing nerve fibers suggests a role for acetylcholine in both contractility and secretion in the prostate gland. The colocalization of nitrergic nerves with cholinergic nerves, and the cotransmission of nitric oxide with acetylcholine in cholinergic nerves, has been demonstrated in the prostate glands of various species. Thus, we investigated the effects of acetylcholine on phenylephrine-induced contraction and the correlation between cholinergic transmission and nitric oxide synthase by using isolated prostate strips of rabbits., Materials and Methods: Isolated prostate strips were contracted with phenylephrine and then treated with cumulative concentrations of acetylcholine. Changes in acetylcholine-induced relaxation after preincubation with NG-nitroarginine methyl ester, 7-nitroindazole, and aminoguanidine were measured. The effects of selective muscarinic receptor antagonists were also evaluated., Results: In the longitudinal phenylephrine-contracted strip, the cumulative application of acetylcholine (10(-9) to 10(-4) M) elicited a concentration-dependent relaxation effect. Acetylcholine-induced relaxation was inhibited not only by nitric oxide synthase inhibitors (10 µM L-NAME or 10 µM 7-nitroindazole) but also by 10 µM atropine and some selective muscarinic receptor antagonists (10(-6) M 11-([2-[(diethylamino)methyl]-1-piperdinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one and 10(-6) M 4-diphenylacetoxy-N-methyl-piperidine). In contrast, relaxation was significantly increased by pretreatment of the strips with 10 mM L-arginine., Conclusions: Acetylcholine relaxed phenylephrine-induced contractions of isolated rabbit prostate strips. This relaxation may be mediated via both cholinergic and constitutive nitric oxide synthase with both the M2 and M3 receptors possibly playing key roles.

The bladder is involved in 1% to 3% of all hernia cases. We report a case of a large paraperitoneal bladder hernia (BH) in a 59-year-old man who had a palpable scrotal mass. Several techniques and approaches have been described for managing BHs. We performed a laparoscopic partial cystectomy and herniorrhaphy. This is the first case report on the repair of a large BH by use of a laparoscopic technique in Korea.

Retrograde cystography and computed tomography (CT) are considered the gold standard for investigating bladder and pelvic bone injury. However, these methods can miss extraperitoneal bladder rupture caused by a penetrating bone fragment from a pelvic bone fracture. We experienced a routine conventional cystography and CT scan that failed to identify penetration of the bladder by a bone fragment, which thus delayed optimal treatment. Therefore, different diagnostic methods such as CT cystography or cystoscopy should be considered to rule out penetrating injury by a bony fragment in patients with extraperitoneal bladder rupture.

Background: HEPSIN (HPN) gene is one of the most consistently overexpressed genes in patients with prostate cancer; furthermore, there is some evidence supporting an association between HPN gene variants and the risk of developing prostate cancer. In this study, sequence variants in the HPN gene were investigated to determine whether they were associated with prostate cancer risk in a Korean study cohort., Methods: We evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in the HPN gene with prostate cancer risk and clinical characteristics (Gleason score and tumor stage) in Korean men (240 case subjects and 223 control subjects) using unconditional logistic regression., Results: The statistical analysis suggested that three SNPs (rs45512696, rs2305745, rs2305747) were significantly associated with the risk of prostate cancer (odds ratio (OR)=2.22, P=0.04; OR=0.73, P=0.03; OR=0.76, P=0.05, respectively)., Conclusions: The results of this study suggest that, in Korean men, some polymorphisms in the HPN gene might be associated with the risk of developing prostate cancer.

Background: BMS-663068 is a prodrug of the small-molecule inhibitor BMS-626529, which inhibits human immunodeficiency virus type 1 (HIV-1) infection by binding to gp120 and interfering with the attachment of virus to CD4+ T-cells., Methods: Fifty HIV-1-infected subjects were randomized to 1 of 5 regimen groups (600 mg BMS-663068 plus 100 mg ritonavir every 12 hours [Q12H], 1200 mg BMS-663068 plus 100 mg ritonavir every bedtime, 1200 mg BMS-663068 plus 100 mg ritonavir Q12H, 1200 mg BMS-663068 Q12H plus 100 mg ritonavir every morning, or 1200 mg BMS-663068 Q12H) for 8 days in this open-label, multiple-dose, parallel study. The study assessed the pharmacodynamics, pharmacokinetics, and safety of BMS-663068., Results: The maximum median decrease in plasma HIV-1 RNA load from baseline ranged from 1.21 to 1.73 log(10) copies/mL. Plasma concentrations of BMS-626529 were not associated with an antiviral response, while low baseline inhibitory concentrations and the minimum and average steady-state BMS-626529 plasma concentrations, when adjusted by the baseline protein binding-adjusted 90% inhibitory concentration (inhibitory quotient), were linked with antiviral response. BMS-663068 was generally well tolerated., Conclusions: Administration of BMS-663068 for 8 days with or without ritonavir resulted in substantial declines in plasma HIV-1 RNA levels and was generally well tolerated. Longer-term clinical trials of BMS-663068 as part of combination antiretroviral therapy are warranted. Clinical Trials Registration.NCT01009814.

Purpose: Chronic inflammation has been considered a potential risk factor for prostate cancer. Toll-like receptors (TLRs) are important in the innate immune response to pathogens and in cross talk between innate immunity and adaptive immunity. In this study, sequence variants in the TLR4 gene were investigated to determine whether they were associated with prostate cancer risk in a Korean cohort., Methods: An association study between 11 single-nucleotide polymorphisms (SNPs) of the TLR4 gene and prostate cancer was performed in 463 Korean male subjects including 240 prostate cancer patients and 223 healthy controls. SNPs were genotyped using the TaqMan assay, and their association with the risk of prostate cancer was evaluated using logistic regression analysis., Results: The statistical analysis revealed that one SNP at the 3'UTR (rs11536889) showed significant association with the risk of prostate cancer (P (corr) = 0.005, OR = 1.81). One common haplotype (ht2) was also significantly associated with the risk of prostate cancer (P (corr) = 0.009, OR = 1.77). However, further analysis showed no association between any of the SNPs and prostate cancer prognostic factors such as the Gleason score or tumor stage., Conclusions: The findings of this study suggest that polymorphisms of the TLR4 gene might be associated with the risk of prostate cancer in Korean men.

Purpose: We investigated the influence of overweight on 24-hour urine chemistry studies and recurrent urolithiasis (UL) in children., Materials and Methods: A retrospective cohort study was designed to assess children who presented with UL at a pediatric institution between 1985 and 2010. We calculated body mass index percentile (BMIp) adjusted for gender and age according to the 2007 Korean Children and Adolescents Growth Chart and stratified the children into 3 BMI categories: lower body weight (LBW, BMIp≤10), normal BW (NBW, 10

The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment (10(-8)~10(-6) M) decreased the contractile responses induced by PE (10(-9)~10(-4) M) and Ach (10(-9)~10(-4) M) in a dose-dependent manner. Melatonin (10(-7) M) also blocked contraction induced by high KCl ([KCl](ECF); 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10(-7) M) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 (10(-11)~10(-7) M). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.

Purpose: Following the introduction of medical therapy for benign prostatic hyperplasia (BPH), we determined the effect of the change in trends in medical therapy on the indication and outcome of surgical intervention for BPH., Materials and Methods: We compared the basic characteristics of, weight of resected tissue of, transfusions in, and postoperative complications of patients who underwent surgery between 1985 and 1989 (before the advent of medical therapy for BPH), between 1995 and 1999 (when medical therapy was developed and became widely used as alternative treatment), and between 2005 and 2009 (when medical therapy superseded surgical intervention to become first-line treatment and when combination therapy became widely adopted)., Results: At our institution, the mean age and BMI of patients increased over the past two decades (p<0.001). Hypertension, operation history, and other comorbidities also increased significantly (p<0.001, p=0.005, and p<0.001, respectively). The indications for surgery in 1985 to 1989, 1995 to 1999, and 2005 to 2009 were as follows: acute urinary retention in 34.7%, 20.2%, and 15.1% of patients and symptomatic deterioration in 61.1%, 72.3%, and 73.0% of patients, respectively. Prostate volume and the weight of resected tissue increased from 34.4±14.5 ml to 61.3±32.4 ml and from 7.2±6.4 g to 10.8±7.6 g, respectively, over two decades. Patients who underwent surgery in 2005 to 2009 had their catheters removed earlier (p<0.001). Secondary hemorrhage within four postoperative weeks and repeat transurethral resection of the prostate within 1 year decreased significantly (p=0.03 and p=0.003, respectively). No statistically significant change in impaired detrusor contractility was found (p=0.523)., Conclusions: Although patients who underwent surgery were older after widespread use of medical therapy for BPH, advancements in surgical techniques have benefitted these patients.

Background: We aimed to evaluate the effectiveness of an oral cavity cancer visual screening program conducted in a tertiary academic medical center. We also wanted to determine which group of participants was at greater risk of contracting oral cavity cancer., Methods: Participants were first asked to relate their personal habits during the past 6 months. Visual screening of the oral cavity was then performed under adequate lighting and with proper instruments., Results: From March 2005 to January 2010, 13,878 participants were enrolled in this study. The average age was 54.6 years. Positive lesions were identified in 726 participants (5.2%), and 282 of those participants (2.1%) had oral cavity cancers confirmed. The sensitivity and specificity of this study were 98.9% and 98.7%, respectively. Those participants who were habitual smokers, alcohol consumers, and betel quid chewers had the highest risk of developing oral cavity cancer when compared with those who did not have these habits (odds ratio=46.90, 95% confidence interval=33.15-66.35, p<0.001)., Conclusion: The oral screening program conducted in a tertiary medical center was effective. We suggest that individuals aged ≥40 years or who are habitual cigarette smokers, alcohol consumers, and betel quid chewers should receive oral screening regularly so that potential oral cancer can be detected as early as possible., (Copyright © 2011. Published by Elsevier B.V.)

Objective: To examine the independent effect of metabolic syndrome (MS) on nephrolithiasis (NL) even with changes in MS status over time., Methods: From 2002-2003, 3872 men who were reexamined annually or biannually until 2009 were enrolled in the analysis and observed for development of NL. The examination included anthropometric measurements, biochemical measurement, and kidney ultrasonography (US). A standard Cox proportional hazards model and a time-dependent Cox model were used to calculate the adjusted hazard ratio in the NL model., Results: After adjusting for age, baseline glomerular filtration rate, and uric acid level, MS at baseline was associated with a significantly increased risk of NL (HR, 1.771; 95% confidence interval, 1.157-2.711). MS over time as a time-dependent variable also predicted the development of NL (HR, 1.678; 95% CI, 1.151-2.447) after adjusted baseline covariate. After adjustment for potential confounding factors, there was a significant stepwise increase in risk of NL, with each additional MS trait compared with those with no traits of MS at baseline and follow-up. As the numbers of MS traits at baseline and follow-up increased, the urine pH of participants at baseline and follow-up decreased significantly (P <.01). The prevalence of NL in participants with continual MS (6.6%) was higher than those with resolved MS, and continual MS was an independent factor to predict NL., Conclusion: Our findings suggest that MS is significantly associated with increased risk of developing urine acidification, even with changes in status of MS observed during follow-up., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To investigate whether altered prostate specific antigen (PSA) levels due to individual prostate growth may affect the PSA velocity (PSAV)., Materials and Methods: Between January 2000 and December 2009, a total of 159 men with at least 2 transrectal ultrasonography (TRUS) procedures and concurrent PSA measurements underwent prostate biopsy because of suspicion of prostate cancer. We measured PSAV, prostate volume velocity (PVV), PSA density (PSAD), PSAD velocity (PSADV), and PSAV per initial volume. We then classified the total group into a prostate cancer (PC) group and non-PC group, and compared the 2 groups. We investigated which variables were exact to predict prostate biopsy using univariate and multivariate analyses, and assessed the diagnostic performance using the receiver operating characteristic (ROC) curve., Results: PVV showed a positive correlation with initial prostate volume in the total and non-PC group; PVV showed a positive correlation with PSAV, and initial prostate volume correlated with PSAV in the non-PC group. The PC group showed smaller prostate volumes, higher PSAD, higher PSADV, higher PSAV per initial volume, and longer follow-up periods. After adjusting for confounding factors, the odds ratios of prostate cancer across the quartile of PSAVD were 1, 1.889, 3.226, and 7.125 (P for trend = .007), and PSAV per initial volume were 1, 2.924, 2.937, and 7.536 (P for trend = .031). On the ROC curve, the areas under the curves (AUC) of PSAV per initial volume were higher than for PSAV and PSADV., Conclusion: Altered PSA levels due to individual prostate growth may affect the use of PSAV to predict prostate biopsy outcomes in follow-up., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To identify whether the genetic variations in HNF1B are associated with the development of prostate cancer in Korean patients. Genome-wide association studies have found the HNF1B gene at 17q12 to be a major causal gene for the risk of prostate cancer., Methods: We evaluated the association of 47 single nucleotide polymorphisms (SNPs) in the HNF1B gene with prostate cancer risk and clinical characteristics (Gleason score and tumor stage) in Korean men (240 case subjects and 223 control subjects) using unconditional logistic regression analysis., Results: Of the 47 SNPs, 14 were associated with prostate cancer risk (P = .002-.02); 9 SNPs were associated with a lower risk of prostate cancer (odds ratio 0.67-0.71, P = .005-.05), and 5 SNPs were associated with a greater risk of disease (odds ratio 1.49-1.51, P = .002-.02). In an analysis involving only patients with prostate cancer, 1 SNP (rs11868513) in the HNF1B gene was more frequent in patients with tumors with a greater stage than in those with a lower tumor stage. Two SNPs (rs4430796 and rs2074429) and 1 haplotype (Block3&#95;ht1) were more frequent in patients with Gleason score of ≥7 than in those with Gleason score <6., Conclusion: As in studies from other populations, our findings indicate that HNF1B is also associated with prostate cancer risk in the Korean population., (Copyright © 2011. Published by Elsevier Inc.)

Purpose: To retrospectively evaluate the effect of post-prostate-biopsy hemorrhage on the interpretation of magnetic resonance diffusion-weighted (MRDW) and magnetic resonance spectroscopic (MRS) imaging in the detection of prostate cancer. We also investigated the optimal timing for magnetic resonance examination after prostate biopsy., Materials and Methods: We reviewed the records of 135 men. All patients underwent prostate magnetic resonance imaging (MRI). The prostate was divided into eight regions according to the biopsy site. Subsequently, we measured hemorrhage on apparent diffusion coefficient (ADC) values and (choline+creatinine)/citrate ([Cho+Cr]/Cit) ratios in the same regions on the MRI. We investigated the effect of hemorrhage at ADC values and (Cho+Cr)/Cit ratios on MRI and the relationship between prostate biopsy results and MRI findings., Results: The mean patient age was 68.7 years and the mean time between biopsy and MRI was 23.5 days. The total hemorrhagic score demonstrated no significant associations with intervals from biopsy to MRI. Higher hemorrhagic scores were associated with higher ADC values, prostate cancer, and noncancer groups, respectively (p<0.001). ADC values were lower in tumors than in normal tissue (p<0.001), and ADC values were inversely correlated with tumor Gleason score in biopsy cores (p<0.001). However, (Cho+Cr)/Cit ratios did not exhibit any association with prostate biopsy results and hemorrhage., Conclusions: Hemorrhage had no significant associations with the interval from biopsy to MRI. ADC values may help to detect prostate cancer and predict the aggressiveness of cancer; however, it is important to consider the bias effect of hemorrhage on the interpretation of MRDW imaging given that hemorrhage affects ADC values.

Purpose: To analyze the independent effect of metabolic syndrome (MS) on nephrolithiasis (NL) despite differences in gender compared with the known lithogenic factors., Materials and Methods: From 1995 to 2009, 40,687 Koreans were enrolled in the study and observed for the development of NL at a health promotion center. The examination included anthropometric and biochemical measurements as well as kidney ultrasonography. A student's t-test or chi-square test was used to characterize the participants and a standard Cox proportional hazards model was used to calculate the adjusted odds ratio of lithogenic risk factors in the NL model., Results: The mean age of the study cohort was 44.9 years (range, 13-100 years), and 22,540 (55.4%) of the cohort was male. The incidence of NL was 1.5% (609 participants), with males exhibiting a higher incidence than females (1.9% vs 1.0%, p<0.01). Among the total cohort, MS as well as each trait of MS were risk factors for NL. In males, high body mass index (BMI), high blood pressure, and abnormal glucose metabolism were significant lithogenic factors, whereas in females, lithogenic factors included only high BMI and abnormal glucose metabolism., Conclusions: MS is a significant lithogenic factor compared with other lithogenic factors. There was a correlated change in the prevalence of MS and NL and MS traits in Korea.

Objectives: To determine whether resistin, a novel adipokine, induces prostate cancer cell proliferation. To identify the mechanisms underlying the activation of prostate cancer cells by resistin., Materials and Methods: Semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed to investigate the intensity of prostate epithelial resistin expression. Human full-length resistin gene (RETN) was transfected into the PC-3 cells using the pEGFP-N1 vector to assess the effect of overexpression of resistin in prostate cancer cell line PC-3. Various concentrations of human recombinant protein resistin were added to the hormone-insensitive prostate cancer cell lines PC-3 and DU-145 for 48 h, and cell proliferation was assessed by a water-soluble tetrazolium salt assay., Results: Human prostate cancer cell lines PC-3 and DU-145 were found to express the human resistin mRNA. Resistin protein was strongly detected in high-grade prostate cancer tissue, whereas BPH or low-grade prostate cancer tissue revealed fainter expression of resistin. Cell proliferation was stimulated by both the full-length resistin gene overexpression and resistin treatment. Akt phosphorylation occurred after addition of resistin to PC-3 and DU-145 cells. LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited PC-3 and DU-145 cell proliferation after resistin treatment., Conclusions: Resistin is expressed in human prostate cancers. Resistin induces prostate cancer cell proliferation through PI3K/Akt signalling pathways. The proliferative effect of resistin on prostate cancer cells may account in part for prostate cancer progression., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Purpose: Numerous trials have been conducted to develop new treatment regimens for superficial and invasive bladder cancer, because there is an urgent need to identify novel agents to prevent the recurrence and progression of these cancers. We evaluated the prognostic and biological significance of mTOR pathway-related markers in patients with bladder cancer who had undergone transurethral resection of their bladder tumors and radical cystectomy., Materials and Methods: We retrieved 208 bladder cancer specimens collected from patients between 1989 and 2007 and constructed a tissue microarray comprising 208 tumor samples and 25 benign urothelium samples. Immunohistochemical staining was performed for mTOR, phosphorylated (phos) S6, and phos4E-BP1. The pattern, percentage, and intensity of staining for all three markers were evaluated., Results: The median age at diagnosis of the patient cohort was 67 years (range: 29-87 years), and the median follow-up was 72 months (range: 1-257 months). The expression of phos4E-BP1 was higher in the bladder cancer cohort than in the benign cohort, whereas phosS6 expression was lower in the bladder cancer cohort than in the benign cohort. The expression of phosS6 was significantly higher in high-grade bladder cancer (p<0.01). There was a significant positive correlation between the H-scores of mTOR and phos4E-BP1 (coefficient of correlation, r=0.37, p<0.01) as well as between the H-scores of mTOR and phosS6 (r=0.17, p<0.05). In the multivariate analysis, strong phosS6 expression predicted shorter progression (p<0.01; hazard ratio [HR], 2.516) and disease-specific survival (p<0.01; HR, 2.396) but not overall survival (p=0.112), whereas strong phos4E-BP1 expression was a predictor of disease-specific survival (p<0.05; HR, 2.105). Moreover, strong phosS6 expression predicted shorter recurrence-free (p<0.05) and progression-free (p<0.05) survival in the superficial bladder cancer cohort., Conclusions: Our results demonstrate that mTOR pathway activation, as assessed by phos4E-BP1 phosphorylation, is related to bladder cancer tumorigenesis and that S6 protein phosphorylation is associated with a high level of disease recurrence and progression and poor cancer-specific survival.

Purpose: There are various causes of ureter calculi, and genetic factors are known to play a role. Interleukin-1β (IL-1β) and calcium-sensing receptor (CaSR) genes are related to hypercalciuria, and urokinase is related to the formation of calcium oxalate stones. This study investigated polymorphisms in IL-1β, CaSR, and urokinase in patients with urolithiasis and healthy controls., Materials and Methods: Urolithiasis patients treated at Chung-Ang University Hospital were enrolled from January 2007 to December 2008. The control group of volunteers displayed normal urinalysis findings in the health screening, no stones identified by ultrasonography, and no history of urolithiasis. DNA extracted from peripheral blood was analyzed by the polymerase chain reaction. Patients were genetically screened for mutations in IL-1β (484 urolithiasis patients, 208 controls), CaSR (433 urolithiasis patients, 197 controls), and urokinase (370 urolithiasis patients, 167 controls). Stone metabolic study was done to see the differences between the metabolic factors and to discern normal genes from polymorphic genes., Results: According to the genotype frequency and allele frequency analysis, there were no statistically significant differences between IL-1β, CaSR, and urokinase genes. Also, the analysis between genotypes and metabolic factors did not show statistically significant differences between the three genes., Conclusions: In Korean urolithiasis patients, IL-1β, CaSR, and urokinase gene polymorphisms do not differ from those of healthy individuals. A larger-scale study is needed to confirm the need for other genetic markers of urolithiasis.

Objective: To investigate the expression and regulation of human β-defensin-2 (HBD-2) in the prostate., Patients and Methods: Normal human prostate epithelial cell line (RWPE-1), human prostate cancer cell lines (DU-145, PC-3), and paraffin-embedded prostate tissue from patients with benign prostatic hyperplasia (BPH) were analysed by RT-PCR and immunohistochemical staining. HBD-2 expression was also analysed by RT-PCR and ELISA in RWPE-1 cells treated with lipopolysaccharide (LPS). Nuclear factor-κB (NF-κB) activation was assessed by IκBα immunoblotting and electrophoretic mobility shift assay (EMSA)., Results: BPH tissue and all of the tested prostate cell lines other than PC-3 constitutively express HBD-2 mRNA. HBD-2 protein was strongly detected in prostate gland tissue surrounded by inflammatory cells including macrophages. Exposure to LPS induced HBD-2 upregulation and NF-κB activation, as assessed by IκBα phosphorylation and degradation in RWPE-1 cells. Bay11-7082, an NF-κB inhibitor prevented LPS-induced HBD-2 production in RWPE-1 cells., Conclusions: Prostate epithelial cells may constitutively express HBD-2, and its expression was upregulated by LPS. Our data indicate that HBD-2 may be an important immunomodulatory factor in prostate function. Expression of HBD-2 in normal prostates and the potential role of HBD-2 in prostatitis and BPH should be addressed in the future., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

The aim of this study was to determine the impact that age and comorbidity status have on both overall and bladder cancer-specific survival of bladder cancer patients. We obtained medical information pertaining to a population of 528 patients with newly diagnosed bladder cancer from Chung-Ang University Hospital cancer registry. The Adult Comorbidity Evaluation-27 (ACE-27) test, which has been previously validated in adult cancer patients, was used to assess comorbidity. We evaluated differences in the demographic and clinical characteristics of included patients, as well as differences in the treatments they received after categorizing them by age. The median age at the time of bladder cancer diagnosis of the entire cohort was 63 years, and the median follow-up time was 97 months. Of the 528 patients who were included in our study, 303 had at least one comorbid condition and 249 died during the follow-up period. When patients were stratified by age, we found that older patients had a higher proportion of severe comorbidities (P < 0.01) than younger patients, and that a lower proportion of them underwent radical cystectomy for invasive bladder cancer (IBC) (P < 0.01). By multivariate analysis, we found that older age was predictive of lower overall survival (OS) and bladder cancer-specific survival (BCSS) rates among patients with superficial bladder cancer (SBC) and of lower OS rates among patients with IBC. We also found that moderate-severe comorbidity status and treatment through a bladder-conserving approach were predictive of lower OS and cancer-specific survival rates among patients with IBC. The disparity between overall deaths and bladder cancer deaths was shown in SBC and increased along with age and higher comorbidity. Age and comorbidity were found to be independent predictive factors of OS and BCSS among bladder cancer patients, and explained the disparity that we observed between overall bladder cancer-specific mortality rates.

The synthetic, tension-free midurethral sling procedure using transobturator tape (TOT) was introduced in 2001 and has become the most widely used procedure for the treatment of female urinary incontinence worldwide. However, infectious complications associated with erosions have occasionally been reported because of a foreign body reaction to the polypropylene mesh. We observed a case of a bilateral recurrent thigh abscess manifesting 5 years after a TOT sling procedure. The patient had recurrent thigh abscesses with repeated incisions and drainages in the past 1 year. Five months earlier, she had undergone a procedure to remove the eroded suburethral mesh, but incompletely. The right thigh abscess recurred, and ultimately the residual mesh was completely excised with abscess drainage. Complete mesh removal is very important to prevent abscess recurrence, and it is necessary for any urologist treating women who have undergone the TOT procedure to be aware of the possibility of abscesses occurring for a long time after the operation.