Testosterone deficiency and the risk of anemia: A propensity score-matched analysis.

OBJECTIVE: There are little data on the endogenous testosterone effect on hemoglobin or hematocrit. Moreover, these data are limited by a cross-sectional study design, a small participant number, and no adjustment for confounding factors. Therefore, the present study was conducted to address the aforementioned limitations of previous studies using a large dataset and propensity score matched analysis. MATERIALS AND METHODS: Men who underwent health check-up were analyzed. Participants were divided into two groups using the cut-off testosterone value of 3.5 or 3.0 ng/ml according to a previous definition of testosterone deficiency. Using the cutoff testosterone value of 3.5 ng/ml, 966 cases (testosterone levels <3.5 ng/ml) and 7402 controls (testosterone level ≥3.5 ng/ml) were included, but following propensity score matching, there were 966 cases and 1932 controls. Using the cutoff testosterone value of 3.0 ng/ml, 444 cases (testosterone levels <3.0 ng/ml) and 7924 controls (testosterone level ≥3.0 ng/ml) were included, but following propensity score matching, there were 444 cases and 888 controls. RESULTS: After matching, the groups were evenly distributed with respect to age, body mass index, estimated glomerular filtration rate, hypertension, and diabetes in both data sets. After matching, the mean Hb and Hct were significantly lower and the incidence of anemia was significantly greater in the case compared to the control in both data sets. The relative risk of anemia in the case was 2.4 compared to the control in both data sets. CONCLUSION: Screening for anemia in patients with testosterone deficiency would be needed and vice versa.

Association of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Lymphocyte-to-Monocyte Ratio with Benign Prostatic Hyperplasia: A Propensity Score-Matched Analysis.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have recently been proposed as easily accessible inflammatory biomarkers and as surrogate markers for metabolic disease, cardiovascular disease, and malignancies, including prostate cancer. However, scant studies have investigated the association of NLR, PLR, and LMR with benign prostatic hyperplasia (BPH). METHODS: Data from 8,727 middle-aged men who had participated in a health checkup were analyzed. BPH was defined as prostate volume ≥30 mL, International Prostate Symptom Score > 7, and maximal flow rate <15 mL/s. Propensity score matching was considered for 269 men with BPH (cases), and 7,136 men with no BPH (controls), but ultimately, propensity scores were matched at a 2:1 ratio of controls to cases (538 men in the control group and 269 men in the case group). RESULTS: After propensity score matching, age, International Index of Erectile Function-5, testosterone, and number of metabolic syndrome component variables were evenly distributed and did not differ significantly between the groups. After matching, PLR and LMR were not significantly different between the 2 groups. However, NLR was significantly higher in the case group than in the control group (median [interquartile range]: 1.4 [1.1; 1.8] vs. 1.5 [1.2; 1.9]; p = 0.024) after matching. CONCLUSION: High NLR was significantly associated with the presence of BPH. Our results suggest the possible effect of inflammation on BPH development. A prospective study is needed to investigate the potential role of NLR as a candidate biomarker of BPH.

Practice Patterns of Korean Urologists Regarding Positive Surgical Margins after Radical Prostatectomy: a Survey and Narrative Review.

BACKGROUND: There is no clear consensus on the optimal treatment with curative intent for patients with positive surgical margins (PSMs) following radical prostatectomy (RP). The aim of this study was to investigate the perceptions and treatment patterns of Korean urologists regarding the resection margin after RP. METHODS: A preliminary questionnaire was prepared by analyzing various studies on resection margins after RP. Eight experienced urologists finalized the 10-item questionnaire. In July 2019, the final questionnaire was delivered via e-mail to 105 urologists in Korea who specialize in urinary cancers. RESULTS: We received replies from 91 of the 105 urologists (86.7%) in our sample population. Among them, 41 respondents (45.1%) had performed more than 300 RPs and 22 (24.2%) had completed 500 or more RPs. In the question about whether they usually performed an additional biopsy beyond the main specimen, to get information about surgical margin invasion during surgery, the main opinion was that if no residual cancer was suspected, it was not performed (74.7%). For PSMs, the Gleason score of the positive site (49.5%) was judged to be a more important prognostic factor than the margin location (18.7%), multifocality (14.3%), or margin length (17.6%). In cases with PSMs after surgery, the prevailing opinion on follow-up was to measure and monitor prostate-specific antigen (PSA) levels rather than to begin immediate treatment (68.1%). Many respondents said that they considered postoperative radiologic examinations when PSA was elevated (72.2%), rather than regularly (24.4%). When patients had PSMs without extracapsular extension (pT2R1) or a negative surgical margin with extracapsular extension (pT3aR0), the response 'does not make a difference in treatment policy' prevailed at 65.9%. Even in patients at high risk of PSMs on preoperative radiologic screening, 84.6% of the respondents said that they did not perform neoadjuvant androgen deprivation therapy. Most respondents (75.8%) indicated that they avoided nerve-sparing RP in cases with a high risk of PSMs, but 25.7% said that they had tried nerve-sparing surgery. Additional analyses showed that urologists who had performed 300 or more prostatectomies tended to attempt more nerve-sparing procedures in patients with a high risk of PSMs than less experienced surgeons (36.6% vs. 14.0%; P = 0.012). CONCLUSION: The most common response was to monitor PSA levels without recommending any additional treatment when PSMs were found after RP. Through this questionnaire, we found that the perceptions and treatment patterns of Korean urologists differed considerably according to RP resection margin status. Refined research and standard practice guidelines are needed.

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.

The prevalence and risk factors of nocturia in China, South Korea, and Taiwan: results from a cross-sectional, population-based study.

PURPOSE: To examine the prevalence, symptomatology, and risk factors for nocturia using data from an internet-based questionnaire conducted in China, South Korea, and Taiwan. METHODS: Data from a cross-sectional, population-representative, internet-based study conducted among men and women aged ≥ 40 years were analysed post hoc. Nocturia prevalence and bother were analysed by sex and age group, and with regard to comorbid conditions and lower urinary tract symptoms (LUTS). Multivariate and univariate logistic regression models to identify risk factors for nocturia were constructed, with nocturia involving ≥ 2 nocturnal voids as the dependent variable. RESULTS: Among the 8284 participants, the prevalence of nocturia involving ≥ 1, ≥ 2, or ≥ 3 voids was slightly higher for women (76.1, 37.3, and 17.5%, respectively) compared with men (74.0, 34.5, and 15.5%, respectively). The prevalence and associated bother of nocturia increased with age. Greater proportions of patients with comorbid conditions or wet/more severe overactive bladder syndrome (OAB) experienced nocturia than those without. Multivariate analysis identified that female sex, age > 60 years, diabetes, cardiac disease, body mass index, International Prostate Symptom Score (IPSS) voiding score, stress urinary incontinence, wet OAB, and Hospital Anxiety And Depression Scale (HADS) anxiety score were associated with ≥ 2 nocturnal voids. Hypertension was associated with ≥ 2 nocturnal voids in women but not men, and alcohol consumption in men but not women. CONCLUSIONS: Nocturia is a common and bothersome condition affecting a large proportion of men and women aged ≥ 40 years in China, South Korea, and Taiwan. Factors associated with nocturia included age, sex, comorbid conditions, and LUTS. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT02618421.

Radical prostatectomy for clinically localized prostate cancer in patients aged 75 years or older: comparison with primary androgen deprivation therapy.

OBJECTIVE: To determine whether radical prostatetomy (RP) is suitable for prostate cancer patients with age ≥75 years in comparison to primary androgen deprivation therapy (PADT). PATIENTS AND METHODS: A cohort study was conducted in clinically localized prostate cancer patients with ≥75 years of age who underwent RP or PADT at six institutions from 2005 to 2013. Patients who had less than 12 months of follow-up, or received neoadjuvant or adjuvant therapy were excluded. We compared clinical characteristics, cancer-specific and overall survivals, and post-treatment complication rates between two groups. RESULTS: We included 92 and 99 patients in the RP and PADT groups, respectively. In survival analyses, there were no significant differences in cancer-specific and overall survivals (p = .302 and .995, respectively). The incidence of serious adverse events (cardio- or cerebrovascular event, or bone fracture) was higher in the PADT group (p = .001). Multivariable analysis showed that PADT had a worse effect on the serious adverse events (OR 10.12, p = .038). CONCLUSIONS: In selected elderly patients, RP was safe and effective for treatment of localized prostate cancer, as compared to PADT. Surgical treatment options should be considered in elderly patients with respect to life expectancy, rather than chronological age.

Association of lower urinary tract symptoms and OAB severity with quality of life and mental health in China, Taiwan and South Korea: results from a cross-sectional, population-based study.

BACKGROUND: Lower urinary tract symptoms (LUTS) and overactive bladder (OAB) symptoms have a substantial effect on quality of life (QoL). We report QoL and mental health results from a LUTS prevalence study in three Asian countries. METHODS: A cross-sectional, population-representative, internet-based study among individuals aged ≥40 years in China, Taiwan and South Korea. Instruments included: Overactive Bladder Symptom Score (OABSS); International Prostate Symptom Score (IPSS); other International Continence Society (ICS) symptom questions; health-related QoL 12-item short-form (HRQoL-SF12v2); Work Limitations Questionnaire (WLQ); Hospital Anxiety and Depression Scale (HADS). Presence of LUTS was determined according to ICS criteria, with three symptom groups (storage, voiding and post-micturition). Post-stratification weighting matched the age and sex population distribution per country. Initial data analyses were based on descriptive statistics. Significance testing undertaken post hoc included: independent-samples t-test (differences in HRQoL between sexes and between individuals with/without LUTS; relationship between HRQoL score and OABSS; differences in HADS anxiety and depression scores between individuals with/without LUTS; association between HADS anxiety/depression scores and OABSS), chi-square test (association between LUTS prevalence and workplace productivity) and analysis of variance (differences in HRQoL score and in HADS anxiety/depression scores between individuals with different symptom groups, association between HADS anxiety/depression scores and IPSS). RESULTS: In total, 8284 participants were included. HRQoL scores were significantly worse (p < 0.001) among individuals with versus without LUTS (ICS criteria): mean physical health domain scores were 61.1 (standard deviation [SD], 20.1) and 76.7 (17.0), respectively; corresponding mental health domain scores were 34.8 (12.7) and 43.7 (10.7). Workplace productivity was best among individuals without LUTS (difficulties reported by 2-3% of individuals), and worst in those with all three ICS symptom groups (difficulties reported by 29-38% of individuals; p = 0.001). Mean HADS scores showed significantly worse (p < 0.001) levels of anxiety and depression among individuals with versus without LUTS: anxiety, 6.5 (SD, 3.7) and 4.0 (3.3); corresponding mean depression scores were 6.8 (4.3) and 4.2 (3.6). Increasing OAB severity was also associated with decreasing HRQoL physical and mental health scores. CONCLUSION: LUTS and increasing OAB severity are both associated with impaired QoL, reduced workplace productivity, and increased tendency towards anxiety and depression. These results highlight the need to ensure that individuals with LUTS receive appropriate, effective treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02618421 , registered 26 November 2015 (retrospectively registered).

A multicenter real-life study of the efficacy of an alpha-blocker with or without anticholinergic agent (imidafenacin) treatment in patients with lower urinary tract symptoms/benign prostatic hyperplasia and storage symptoms.

AIMS: To evaluate the efficacy and safety of combination therapy comprising a short-acting anticholinergic, imidafenacin and an alpha-blocker compared with monotherapy with an alpha-blocker only in men with lower urinary tract symptoms (LUTS) and storage symptoms. METHODS: The 12-week, prospective, double-blind, randomised trial enrolled men with LUTS and storage symptom. The inclusion criteria were a total International Prostate Symptom Score (IPSS) ≥12, an IPSS question 4 score ≥2, ≥8 micturitions in 24 hours, and a prostate volume >20 mL. The primary outcome was a change in the micturition number from baseline. Bladder diary variables, Patient Perception of Intensity of Urgency Scale (PPIUS) scores, IPSS and safety were assessed. RESULTS: Of 260 patients screened, 221 completed the study. Patients were randomly assigned to receive an alpha-blocker only (n=111, group 1) or combination therapy comprising an alpha-blocker and an anticholinergic (n=110, group 2) for 12 weeks. Group 1 and 2 showed significant improvement in their 24-hour micturition numbers (-1.87 and -2.08, respectively), nocturia episodes (-0.48 and -0.53, respectively), total IPSS (-9.9 and -8.8, respectively), and PPIUS scores (-0.19 and -0.24, respectively). Micturition number per 24 hours, daytime frequency, urgency, the PPIUS score, the IPSS question 4 score and IPSS QoL score improved significantly in the combination therapy group, but changes in total IPSS, nocturia episodes, and safety outcomes did not differ significantly between the groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: Compared with treatment with an alpha-blocker alone, combination therapy comprising an anticholinergic and an alpha-blocker showed superior efficacy and its safety was similar in patients with LUTS and storage symptoms.

Radical Prostatectomy in Korean Men Aged 75-Years or Older: Safety and Efficacy in Comparison with Patients Aged 65-69 Years.

Prostate cancer is the most common type of male cancer worldwide. Although radical prostatectomy (RP) is advised for prostate cancer in patients with a life expectancy of more than 10 years by various guidelines, most elderly men still do not undergo the procedure regardless of increasing life expectancy. This study aimed to determine whether RP is suitable for patients with prostate cancer aged 75 years or older. A retrospective study of patients who underwent RP at 6 institutions between 2005 and 2012 was conducted. Patients were divided into 2 groups at the time of surgery: 65-69 years (younger group) and 75 years or older (older group). We compared clinical characteristics, pathological results, complication rates, and recurrence-free survival between the two groups. Compared with the younger group, the older group had significantly higher preoperative serum prostate-specific antigen level, pre- and postoperative Eastern Cooperative Oncology Group (ECOG) performance status grade, hypertension prevalence, and Gleason score at biopsy and RP. However, except urinary incontinence, there were no statistically significant differences in the peri- and post-operative complications. After median follow-up periods of 36 months (younger group) and 40 months (older group), the biochemical recurrence-free survival rates were not significantly different (P = 0.581). Although the urinary incontinence rate was higher in the older group, RP was a suitable option for selected Korean men aged 75 years or older with limited complication rates and excellent outcomes similar to those for patients aged 65-69 years.

Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells.

Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.

Analysis of distress in patients undergoing radical prostatectomy: A multicenter prospective study.

PURPOSE: To analyze the degree of psychological distress experienced pre- and postoperatively in patients who underwent radical prostatectomy after being diagnosed with prostate cancer. MATERIALS AND METHODS: Patients diagnosed with prostate cancer who underwent radical prostatectomy without history of psychiatric disorders were included in this study. The degree of psychological distress was evaluated using hospital anxiety and depression scale (HADS) and distress thermometer (DT) questionnaires preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: Distress was high preoperatively and decreased over the entire period. In addition, HADS-anxiety and HADS-depression scores showed an improved severity, shifting from an abnormal state to a borderline state in some patients. However, the DT score, including emotional problems, spiritual concerns, physical problems, family problems, and practical problems, was slightly higher at 1 month postoperatively compared to preoperatively. Furthermore, even at 12 months postoperatively, about one fifth of patients surveyed had a DT score of 4 or higher, requiring psychiatric intervention. CONCLUSIONS: Before and after radical prostatectomy, a significant number of patients complained of distress such as anxiety, depression, and insomnia, and they needed help from a specialist because of psychological distress even 12 months postoperatively. Therefore, a close evaluation of the patient's psychological distress and supportive treatment are needed during the entire pre- and postoperative period.

Desmopressin add-on therapy for refractory nocturia in men receiving α-blockers for lower urinary tract symptoms.

PURPOSE: Alpha-blockers improve lower urinary tract symptoms associated with benign prostatic obstruction. Nocturia, a storage symptom, is a common complaint in men. However, it does not fully respond to α-blocker therapy, likely due to its multifactorial pathophysiology. We evaluated the efficacy and safety of desmopressin as add-on therapy for refractory nocturia in men previously treated with an α-blocker for lower urinary tract symptoms. MATERIALS AND METHODS: Eligible patients were men 50 years old or older with lower urinary tract symptoms and persistent nocturia despite α-blocker treatment for a minimum of 4 weeks. The optimum dose of oral desmopressin was determined during a 4-week dose titration period and this dose was maintained for 24 weeks. Flow volume charts, International Prostate Symptom Score total and subscores, uroflowmetry and post-void residual urine volume were assessed. RESULTS: A total of 216 patients were enrolled in the study. Of these patients there were 158 (76%) with nocturnal polyuria, 15 (7.2%) with decreased nocturnal bladder capacity and 35 (16.8%) with nocturia due to both causes. The number of nocturnal voids significantly decreased from a baseline mean of 7.0 to 5.7 episodes for 3 days at the 24-week visit. The average International Prostate Symptom Score total and subscore significantly decreased by 4 weeks and were maintained at 24 weeks. In patients younger than 65 years, International Prostate Symptom Score voiding subscores were significantly improved at 24 weeks compared to those age 65 years or older. CONCLUSIONS: Desmopressin add-on therapy for refractory nocturia in men previously treated with an α-blocker for lower urinary tract symptoms improved voiding symptoms as well as nocturia, storage symptoms.

Assessments of the quality of randomized controlled trials published in International Journal of Urology from 1994 to 2011.

OBJECTIVES: Randomized controlled trials are one of the most reliable resources for assessing the effectiveness and safety of medical treatments. Low quality randomized controlled trials carry a large bias that can ultimately impair the reliability of their conclusions. The present study aimed to evaluate the quality of randomized controlled trials published in International Journal of Urology by using multiple quality assessment tools. METHODS: Randomized controlled trials articles published in International Journal of Urology were found using the PubMed MEDLINE database, and qualitative analysis was carried out with three distinct assessment tools: the Jadad scale, the van Tulder scale and the Cochrane Collaboration Risk of Bias Tool. The quality of randomized controlled trials was analyzed by publication year, type of subjects, intervention, presence of funding and whether an institutional review board reviewed the study. RESULTS: A total of 68 randomized controlled trial articles were published among a total of 1399 original articles in International Journal of Urology. Among these randomized controlled trials, 10 (2.70%) were from 1994 to 1999, 23 (4.10%) were from 2000 to 2005 and 35 (4.00%) were from 2006 to 2011 (P = 0.494). On the assessment with the Jadad and van Tulder scale, the numbers and percentage of high quality randomized controlled trials increased over time. The studies that had institutional review board reviews, funding resources or that were carried out in multiple institutions had an increased percentage of high quality articles. CONCLUSIONS: The numbers and percentage of high-quality randomized controlled trials published in International Journal of Urology have increased over time. Furthermore, randomized controlled trials with funding resources, institutional review board reviews or carried out in multiple institutions have been found to be of higher quality compared with others not presenting these features.

Inhibition of androgen receptor expression with small interfering RNA enhances cancer cell apoptosis by suppressing survival factors in androgen insensitive, late stage LNCaP cells.

INTRODUCTION: The aim was to evaluate the changes of androgen receptor (AR) expression quantitatively and to identify influence of AR on cancer related survival markers in LNCap cell line. MATERIALS AND METHODS: We compared expressions of AR, heat shock protein 27 (HSP27), clusterin (CLU), glucose-related protein 78 (GRP78), and cellular FLICE-like inhibitory protein (c-FLIP) and their genes between es-LNCaP (less than 33 times subcultured, L-33), ls-LNCaP (over 81 times subcultured, H-81), and si-LNCaP (AR siRNA transfected ls-LNCaP) by Western blotting and RT-PCR. RESULTS: The expressions of AR, HSP27, CLU, GRP78, and c-FLIP were increased in ls-LNCaP compared with es-LNCaP (AR, 157%; HSP27, 132%; CLU, 146%; GRP78, 138%; c-FLIP, 152%). However, in si-LNCaP cell line, protein expressions were reversed to the level of es-LNCaP cell lines (25, 102, 109, 98, and 101%), and gene expressions on real-time PCR were also reversed to the expression level of es-LNCaP (ls-LNCaP: 179, 156, 133, 123, and 167%; si-LNCaP: 22, 93, 103, 112, and 107%). CONCLUSIONS: This finding suggests that androgen receptor can be related to the increased expression of cancer related survival markers such as HSP27, GRP78, CLU, and c-FLIP in late stage prostate cancer, and also inhibition of AR gene can be a therapeutic target in this stage of cancer.

Dual silencing of Hsp27 and c-FLIP enhances doxazosin-induced apoptosis in PC-3 prostate cancer cells.

We evaluated effect of dual gene silencing of Hsp27 and c-FLIP in doxazosin-induced apoptosis of PC-3 cell. After transfection using Hsp27 and c-FLIP siRNA mixture (dual silencing), doxazosin treatment was done at the concentrations of 1, 10, and 25 µ M. We checked apoptosis of PC-3 cells with and TUNEL staining. We also checked interaction between Hsp27 and C-FLIP in the process of apoptosis inhibition. Spontaneous apoptotic index was 5% under single gene silencing of Hsp27 and c-FLIP and 7% under dual silencing of Hsp27 and c-FLIP. When doxazosin treatment was added, apoptotic indices increased in a dose-dependent manner (1, 10, and 25 µ M): nonsilencing 10, 27, and 52%; Hsp27-silencing: 14, 35, and 68%; c-FLIP silencing: 21, 46, and 78%; dual silencing: 38, 76, and 92%. While c-FLIP gene expression decreased in Hsp27- silenced cells, Hsp27 gene expression showed markedly decreased pattern in the cells of c-FLIP silencing. The knockout of c-FLIP and Hsp27 genes together enhances apoptosis even under 1 µ M, rather than low concentration, of doxazosin in PC-3 cells. This finding suggests a new strategy of multiple knockout of antiapoptotic and survival factors in the treatment of late-stage prostate cancer refractory to conventional therapy.

Safety and efficacy of tamsulosin 0.4 mg as an initial dose in 1,219 Korean patients with moderate to severe lower urinary tract symptoms: data from a phase IV study.

Background: An initial dose of tamsulosin 0.2 mg is frequently prescribed for Asian men. We investigated the safety and efficacy of tamsulosin 0.4 mg as the initial dose in Korean men with moderate to severe lower urinary tract symptoms (LUTSs) in everyday clinical practice. Materials and methods: A phase IV study was conducted in South Korea. Eligible patients were prescribed tamsulosin 0.4 mg for 6 months. We excluded patients with previous exposure to LUTS drugs and patients with an international prostate symptom score (IPSS) < 8. Results: The mean total IPSS, storage subscore, voiding symptoms subscore, and quality of life significantly decreased from 18.0, 10.8, 7.2, and 3.8 to 12.8, 7.5, 5.3, and 2.6, respectively, after 6 months of treatment. The number of nocturia episodes significantly decreased from 3.0 to 2.2 in patients who reported at least 2 nocturia events at baseline. A mean reduction in the IPSS was quantitatively equivalent in all age groups. The mean reduction in the IPSS was greater in the IPSS ≥ 20 group than in the IPSS < 20 group (mean reduction in the total IPSS: -2.6 in the IPSS < 20 group; -9.4 in the IPSS ≥ 20 group). All treatment-emergent adverse events were mild. The most frequently recorded treatment-emergent adverse event was dizziness, which was reported in 22 patients (1.8%). Conclusion: Treatment of LUTS with tamsulosin 0.4 mg as the initial dose for 6 months in Korean men was effective in improving LUTS and showed a favorable safety profile in a real-life setting.

Clinical outcomes of withdrawing one medication from long-term combination therapy comprising α-blocker and 5α-reductase inhibitor for benign prostatic hyperplasia.

PURPOSE: To assess adherence to combination therapy comprising α-adrenergic blocker (AB) and 5α-reductase inhibitor (5ARI) for benign prostatic hyperplasia (BPH) in a real-world setting and whether lower urinary tract symptoms (LUTS) will relapse after discontinuing one medication from long-term combination therapy. METHODS: BPH/LUTS patients receiving initial AB +5ARI combination therapy for at least 1 year between January 2012 and January 2017 were retrospectively analyzed. The patients were classified into DC-AB group (n = 65, AB discontinued) and DC-5ARI group (n = 77, 5ARI discontinued) and followed up. Clinical effects were assessed at baseline and annually using the International Prostatic Symptoms Score (IPSS), quality of life (QoL) index, total prostate volume (TPV), maximal flow rate (Qmax), and prostate-specific antigen (PSA) level. RESULTS: Of total 1783 patients, 809 (45.4%) patients were identified with more than 1-year combination therapy. After withdrawal of one medication from combination therapy, the TPV progression (27.6% vs. - 10.8%; P < 0.001) and the requirement for prostate surgery (14.3% vs. 6.1%; P = 0.038) were significantly higher in the DC-5ARI group than in the DC-AB group. The rate of resuming combination therapy was significantly higher in the DC-5ARI group than in the DC-AB group (38.9% vs. 23.0%; P = 0.009). CONCLUSIONS: Adherence to combination BPH therapy is relatively low. Although patients adhered to combination therapy for more than 1 year, a higher risk of requiring prostate surgery or resuming combination therapy was observed in patients who discontinued 5ARI.

Non-linear association between testosterone and LDL concentrations in men.

BACKGROUND: Contradictory data have been reported about the association between testosterone levels and the levels of low-density lipoprotein cholesterol (LDL). OBJECTIVES: The aim of this study was to elucidate the association between testosterone and LDL levels. MATERIALS AND METHODS: A cross-sectional study was conducted that included 7268 men who had participated in a health examination. Men who took agents that influence serum lipid profiles within the previous 6 months were excluded. A full metabolic work-up and serum testosterone level checks were performed. The main outcome measures included the testosterone level and testosterone <3.5 ng/ml prevalence of each decile of LDL and their polynomial trendlines and the odds ratio (OR) of testosterone <3.5 ng/ml according to the LDL level. RESULTS: The polynomial trendline suggests the inverse association of testosterone with the deciles of triglycerides, the positive association of testosterone with the deciles of high-density lipoprotein cholesterol and the inverted U-shaped association between testosterone and the deciles of LDL. The polynomial trendline suggests a U-shaped curvilinear relationship between the deciles of LDL and the prevalence of testosterone <3.5 ng/ml. The adjusted ORs of testosterone <3.5 ng/ml in men in the lowest and highest deciles were significantly higher than those of men in the 10th-90th deciles of LDL (OR [95% CI], < 10th LDL: 1.4[1.2-1.8]; 10th - 90th LDL: 1.0 [reference]; >90th LDL: 1.3[1.0-1.6]), which reinforces the U-shaped curvilinear relationship between LDL levels and the prevalence of testosterone <3.5 ng/ml. DISCUSSION AND CONCLUSION: Further research is needed to elucidate the association of very low or very high LDL concentrations with circulating testosterone in men.

Single-port transvesical enucleation of the prostate for benign prostatic hyperplasia with severe intravesical prostatic protrusion.

OBJECTIVES: To introduce the surgical techniques of a single-port transvesical enucleation of the prostate (STEP) for enlarged prostates with severe intravesical prostatic protrusion (IPP) presenting with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Our study included 7 patients with prostates larger than 80 mL and with severe IPP who underwent STEP. All the procedures were performed using a home-made single-port device through a 3-cm midline incision at the level three fingerbreadths above the symphysis pubis. Rigid laparoscopic instruments and Harmonic Scalpels(®) were used to enucleate the large adenoma of the prostate. RESULTS: All the procedures were completed satisfactorily, with no intra and early postoperative complications. The mean resected prostatic weight was 54.14 ± 8.38 g, and the mean operative time was 191.86 ± 40.88 min. The mean time for catheterization was 5.29 ± 1.80 days. The postoperative 3-month international prostate symptoms score (IPSS) and maximal flow rate (Qmax) were improved following STEP (IPSS; 23.57 ± 2.15 vs. 11.43 ± 2.44, Qmax; 17.14 ± 3.44 mL/s vs. 6.71 ± 2.29 mL/s). CONCLUSIONS: Laparoendoscopic single-site surgery (LESS) and enucleation of the prostate with rigid laparoscopic instruments might be difficult but is feasible. STEP may be a new treatment option for use in open prostatectomies for enlarged prostates with severe IPP in carefully selected patients.

Efficacy and safety of solifenacin to treat overactive bladder symptoms in patients with idiopathic normal pressure hydrocephalus: an open-label, multicenter, prospective study.

AIMS: To evaluate the efficacy and safety of solifenacin 5 mg to treat voiding symptoms caused by idiopathic normal pressure hydrocephalus (iNPH) after a ventriculoperitoneal (V-P) shunt operation. METHODS: A total of 53 patients diagnosed with iNPH and complaining of voiding symptoms were enrolled. Before treatment with solifenacin (V1), 4 (V2) and 12 (V3) weeks after starting solifenacin overactive bladder symptom score (OABSS), the International Prostate Symptom Score (IPSS), Quality of Life (QoL) score, maximal urine flow rate (Q(max) ), voided volume, and post-voiding residual urine volume (PVR) were measured. An urodynamic study (UDS) was performed at V1 and V3, and the safety of solifenacin was assessed at V1, V2, and V3. RESULTS: Of the 53 patients, 38 patients (71.70%) completed the 12-week clinical trial. The mean patient age was 52.24 ± 10.08 years. OABSS and IPSS were significantly improved. The mean voided volume was 147.18 ± 61.84 ml at V1 and 160.03 ± 62.59 ml at V3 (P < 0.001), and PVR was 64.87 ± 41.11 ml at V1 and 69.05 ± 39.54 ml at V3 (P = 0.009). Of the 31 patients who underwent UDS, 26 patients (83.87%) had detrusor overactivity (DO) at V1, with a mean value of 107.67 ± 18.13 ml. Of the 26 with DO at V1, 22 (84.62%) still had DO at V3. A mean DO of 131.66 ± 15.27 ml was observed at V3 (P < 0.001). The most common adverse effects was dry mouths. CONCLUSIONS: Solifenacin is effective in the treatment of OABS in iNPH patients who underwent the V-P shunt operation. Solifenacin increases bladder capacity causing of DO at UDS.