Comparison of Finasteride and Dutasteride on Risk of Prostate Cancer in Patients with Benign Prostatic Hyperplasia: A Pooled Analysis of 15 Real-world Databases.

PURPOSE: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. MATERIALS AND METHODS: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. RESULTS: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44-1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67-1.14; p=0.310). CONCLUSIONS: Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

The Efficacy and Safety of a Human Perirenal Adipose Tissue-Derived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model.

BACKGROUND: Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients' quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. METHODS: From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 µg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. RESULTS: The mean pain scores in the SVF 20 µl group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group. In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. CONCLUSION: This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.

The significance of the visible tumor on preoperative magnetic resonance imaging in localized prostate cancer.

OBJECTIVES: We investigated the relationship between tumor characteristics and visible tumors on magnetic resonance imaging (MRI) and examined the prognosis of tumor detection on MRI compared with no tumor detection in localized prostate cancer. MATERIALS AND METHODS: We reviewed 214 patients with pT2N0M0 prostate cancer who underwent radical prostatectomy between January 2009 and December 2016. All the patients underwent MRI preoperatively. The patients were divided into 2 groups postoperatively: no visible tumor on the MRI group (n = 96, 44.9%) and visible tumor on the MRI group (n = 118, 55.1%). The visible tumor was defined as Prostate Imaging Reporting and Data System, version 2 Grade ≥ 3 on MRI. Age, prostate-specific antigen, prostate volume, positive surgical margin (PSM), lymphovascular invasion, and biochemical recurrence (BCR) were compared between the 2 groups. We also assessed the relationship between visible tumors on MRI and oncologic characteristics. RESULTS: The visible tumor on the MRI group showed a higher Gleason score ≥4 + 3 [45.8% versus (vs.) 17.7%], high frequency of postoperative PSMs (28.8% vs. 16.7%), and higher BCR rate (17.8% vs. 7.3%) than the no visible tumor on the MRI group. The Kaplan-Meier analysis for BCR-free survival also showed a significant difference (P = 0.006). In multivariate Cox regression analysis, the detection of tumors on MRI was associated with a higher BCR risk [hazard ratio: 3.35; 95% confidence interval (CI): 1.36-8.27; P = 0.009]. We found a positive association between visible tumors on MRI and primary Gleason pattern of ≥4 (odds ratio: 4.31; 95% CI: 2.21-8.40; P < 0.001). CONCLUSIONS: In localized prostate cancer, BCR was significantly more frequent when the tumor was detected on MRI, and a visible tumor on MRI was associated with the Gleason score. Therefore, attention should be paid to the possibility of high-grade prostate cancer when a tumor is detected on MRI before radical prostatectomy, and active follow-up may be needed postoperatively.

Dysregulation of the miRNA biogenesis components DICER1, DROSHA, DGCR8 and AGO2 in clear cell renal cell carcinoma in both a Korean cohort and the cancer genome atlas kidney clear cell carcinoma cohort.

Impairment of microRNA (miRNA) biogenesis may be involved in clear cell renal cell carcinoma (ccRCC). The objective of the present study was to investigate the mRNA levels of important miRNA machinery components, DICER1, DROSHA, DiGeroge syndrome critical region gene 8 (DGCR8), and Argonaute 2 (AGO2), and their correlations with clinicopathological characteristics of ccRCC using mRNA expression data from The Cancer Genome Atlas kidney clear cell carcinoma (TCGA KIRC) cohort and a Korean ccRCC cohort. mRNA levels of DICER1, DROSHA, and DGCR8 were significantly decreased in both cohorts. However, AGO2 was significantly downregulated only in the Korean ccRCC cohort. Additionally, positive correlations were observed between the altered mRNA levels of DICER1 and DROSHA as well as DROSHA and DGCR8 in both cohorts. In the TCGA KIRC cohort, alterations in the mRNA levels of DICER1 were significantly correlated with histological grade. Furthermore, the altered mRNA levels of DGCR8 showed significant associations with sex and histologic grades. However, in the Korean ccRCC cohort, no factors were significantly associated with any clinicopathological parameters, including sex, age, T stage, Fuhrman grade/The International Society of Urological Pathology grade, lymphovascular invasion, and peri-renal fat invasion. Taken together, these findings indicate that DICER1, DROSHA, DGCR8 and AGO2 are significantly dysregulated in ccRCC, suggesting that they are important in the pathophysiology of this malignancy.

Patient-reported Goal Achievement after Treating Male Benign Prostatic Hyperplasia with Alpha-adrenergic Antagonist: A 12-week Prospective Multicenter Study.

PURPOSE: The study was designed to assess and predict patient-reported goal achievement after treatment of benign prostatic hyperplasia (BPH) patients with tamsulosin. MATERIALS AND METHODS: From November 2013 to October 2015, 272 patients initially diagnosed with BPH were prospectively enrolled in nine different centers. Before the treatment, subjective final goals were recorded by all patients. Every four weeks, the treatment outcomes were evaluated using international prostate symptom score (IPSS) and uroflowmetry, and adverse events were recorded. Patient-reported goal achievements were assessed after 12 weeks of treatment. RESULTS: Of the enrolled patients, 179 patients completed the study. The pretreatment patients' goals included the frequency improvement, nocturia improvement, residual urine sense improvement, well voiding, hesitancy improvement, weak urine stream improvement, urgency improvement, and voiding-related discomfort improvement. Of the 179 patients, 129 patients (72.1%) reported that they achieved their primary goals after three months of medical therapy. Logistic regression analysis revealed that pretreatment quality of life (OR = 8.621, 95% CI: 2.154-9.834), and improvement of quality of life (OR = 6.740, 95% CI: 1.908-11.490) were independent predictors of patient-reported goal achievement after tamsulosin monotherapy. CONCLUSION: Overall patient-reported goal achievement after medical therapy for BPH was high and the scores of pretreatment quality of life and improvement of quality of life can be important factors to predict the achievement of treatment goals.

A randomised, placebo-controlled, multicentre, Phase 2 clinical trial to evaluate the efficacy and safety of GV1001 in patients with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the efficacy and safety of three dosing schemes of GV1001 in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Eligible patients were men aged ≥50 years, with an International Prostate Symptom Score (IPSS) of ≥13, maximum urinary flow rate (Qmax ) of 5-15 mL/s, post-void residual urine volume (PVR) of ≤200 mL, and prostate volume of ≥30 mL. After a 4 week run-in period, patients were randomly assigned to one of three treatment schedules: Group 1, GV1001 0.4 mg, 2-week interval; Group 2, GV1001 0.56 mg, 2-week interval; Group 3, GV1001 0.56 mg, 4-week interval) or placebo (Group 4). The eligible patients were administered GV1001 or placebo, for a total of seven intradermal injections that were administered at 2-week intervals at weeks 0, 2, 4, 6, 8, 10, and 12. Treatment continued for 12 weeks, and efficacy was evaluated at weeks 4, 8, 12, 13, and 16. Safety was evaluated throughout the 16-week period. The primary efficacy variable was change from baseline (CFB) in total IPSS. Secondary endpoints were CFB in Qmax , PVR, prostate volume, International Index of Erectile Function score, plasma testosterone level, dihydrotestosterone level, and prostate-specific antigen level. RESULTS: A total of 161 patients were included (Group 1, n = 41; Groups 2-4, n = 40). Most patients (88.8%) received all planned doses of the study treatment. At week 13, a statistically significant difference in the mean CFB in IPSS was seen in GV1001 treatment Groups 1 and 2 vs the control group for the full analysis population (-3.5 [control] vs -7.2 and -6.8 in Groups 1 and 2, respectively; both P < 0.05). There were also statistically significant differences in CFB at weeks 8, 12, 13, and 16 in treatment Groups 1 and 2 vs control in the per-protocol population. There was a statistically significant reduction in prostate gland volume at week 16 vs control in all treatment groups (0.8 [control] vs -4.6, -2.5, and -4.2 mL in Groups 1-3, respectively; all P < 0.05). There were no statistically significant differences found in other secondary outcome measures. Adverse event (AE) reporting was similar across all four groups. No treatment-emergent AEs were considered to be related to the study drug. CONCLUSIONS: The results indicate that GV1001 was effective and well tolerated, and may provide potential beneficial effects in patients with BPH. Compared with medical therapies that require daily dosing, the convenient dosing regimen of GV1001 may provide greater patient adherence. Further investigation of these observations will require large-scale clinical evaluation.

Updated clinical results of active surveillance of very-low-risk prostate cancer in Korean men: 8 years of follow-up.

PURPOSE: Update and reanalysis of our experience of active surveillance (AS) for prostate cancer (PCa) in Korea. MATERIALS AND METHODS: A prospective, single-arm, cohort study was initiated in January 2008. Patients were selected according to the following criteria: Gleason sum ≤6 with single positive core with ≤30% core involvement, clinical stage≤T1c, prostate-specific antigen (PSA)≤10 ng/mL, and negative magnetic resonance imaging (MRI) results. Follow-up was by PSA measurement every 6 months, prostate biopsies at 1 year and then every 2-3 years, and MRI every year. RESULTS: A total of 80 patients were treated with AS. Median follow-up was 52 months (range, 6-96 months). Of them, 39 patients (48.8%) discontinued AS for various reasons (17, disease progression; 9, patient preference; 10, watchful waiting due to old age; 3, follow-up loss; 2, death). The probability of progression was 14.0% and 42.9% at 1 and 3 years, respectively. Overall survival was 97.5%. PCa-specific survival was 100%. Progression occurred in 5 of 7 patients (71.4%) with a prostate volume less than 30 mL, 7 of 40 patients (17.5%) with a prostate volume of 30 to 50 mL, and 5 of 33 patients (15.2%) with a prostate volume of 50 mL or larger. There were 8 detectable positive lesions on follow-up MRI. Of them, 6 patients (75%) had actual progressed disease. CONCLUSIONS: Small prostate volume was associated with a tendency for cancer progression. MRI was helpful and promising for managing AS. Nevertheless, regular biopsies should be performed. AS is a safe and feasible treatment option for very-low-risk PCa in Korea. However, AS should continue to be used in carefully selected patients.

Increased urinary neutrophil gelatinase-associated lipocalin in very-low-birth-weight infants with oliguria and normal serum creatinine.

BACKGROUND: In infants, oliguria is defined as a urine output of <1.5 mL/kg/h. The aim of our study was to assess the impact of oliguria on urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C (CysC) levels in very-low-birth-weight infants (VLBWIs) with a normal serum creatinine (Cr) level. METHODS: Fifty-seven VLBWIs were enrolled in the study. Urinary NGAL, serum CysC and Cr levels and urinary NGAL/Cr ratios were measured. Infants with Apgar scores of >5 at 5 min and/or a serum Cr level of >1.5 mg/dL or those treated for patent ductus arteriosus were excluded. In case of antibiotic treatment, blood and urine samples were collected at ≥48 h after discontinuation of antibiotic treatment. RESULTS: There was a significant difference in gestational age between infants with oliguric episodes during hospitalization and those without, but not in birth weight, perinatal or postnatal factors. Gestational age was negatively correlated with urinary NGAL and serum CysC levels and urinary NGAL/Cr ratio (p < 0.05), whereas postnatal age was negatively correlated with serum Cr level and urinary NGAL/Cr ratio (p < 0.05). Of the 117 urine and blood samples collected, 25 (21.4%) were obtained from neonates with oliguric episodes. After adjusting for gestational age and postnatal age, comparison of samples collected in infants with and without oliguric episodes revealed significant differences in the mean level of urinary NGAL and in the urinary NGAL/Cr ratio, but not in mean serum CysC or serum Cr levels. The urinary NGAL level [area under the curve (AUC) 0.886, 95% confidence interval (CI) 0.814-0.937] and urinary NGAL/Cr ratio (AUC 0.853, 95% CI 0.775-0.911) showed significantly greater discrimination for oliguria than serum CysC (AUC 0.610, 95% CI: 0.515-0.699) or serum Cr (AUC 0.747, 95%CI 0.659-0.823) levels. CONCLUSIONS: Urinary NGAL level and urinary NGAL/Cr ratio were more sensitive markers for the presence of oliguria in VLBWIs with normal serum Cr levels than serum CysC level.

Six-month postoperative urodynamic score: a potential predictor of long-term bladder function after detethering surgery in patients with tethered cord syndrome.

PURPOSE: We evaluated changes in urodynamic parameters of patients with tethered cord syndrome after detethering surgery and investigated factors predicting long-term urological outcome based on a previously described urodynamic scoring system. MATERIALS AND METHODS: A total of 148 patients with tethered cord syndrome underwent detethering surgery at our hospital between January 2005 and March 2011. Of these patients 44 with preoperative and postoperative urodynamic data and a minimum followup of 2 years were included. Urodynamic score was composed of 4 parameters, with the sum ranging from 0 (favorable) to a maximum score of 17 (unfavorable). RESULTS: Mean ± SD age at surgery was 38.0 ± 77.2 months and followup was 57.2 ± 20.6 months. Preoperative symptoms were present in 24 patients. Total urodynamic score at 6 months postoperatively was higher than preoperatively (mean ± SD 5.61 ± 2.71 vs 4.43 ± 3.56, p = 0.033) and remained at a similar value during followup (5.88 ± 3.89). The 6-month postoperative total urodynamic score was significantly lower in the 23 patients with favorable urological outcomes than in those with unfavorable outcomes (3.87 ± 2.02 vs 7.52 ± 1.99, p <0.001), whereas the preoperative urodynamic scores did not differ between these groups. The difference in urodynamic scores between favorable and unfavorable outcome groups became more prominent with time. By regression analysis the total urodynamic score at 6-month followup was a predictor of urological symptoms at last followup (OR 2.763, 95% CI 1.514-5.043, p = 0.001). CONCLUSIONS: Six-month postoperative urodynamic scores accurately predicted the presence of urological symptoms on long-term followup and may be an important predictor of long-term urological outcomes after detethering surgery.