Impact of Circulating Tumor Cell-Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen Transcripts in Different Stages of Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. EXPERIMENTAL DESIGN: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. RESULTS: CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. CONCLUSIONS: PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.

Patients' self-management of adverse events and patient-reported outcomes in advanced renal cell carcinoma treated with targeted therapies: A prospective, longitudinal, observational study.

BACKGROUND: Early intervention to reduce the impact of adverse events (AEs) may improve patients' quality of life and enable optimal treatment duration. METHODS: This nationwide, multicenter, prospective, longitudinal, 1-year observational study investigated patients' self-management of AEs associated with targeted therapy for advanced renal cell carcinoma (RCC) and explored corresponding outcomes, including treatment duration and patient-reported outcomes (PROs). RESULTS: We enrolled 77 advanced RCC patients (mean age 62 years) treated with a first targeted therapy. 210 cases of seven AEs of interest (fatigue, hand-foot syndrome, oral mucosal inflammation, diarrhea, gastrointestinal symptoms, hypertension, and anorexia) were observed. Most AEs were mild to moderate. Overall, 63.4% of patients were identified as managing their AEs well, reporting numerically longer treatment duration and significantly higher PRO scores than patients identified as poor managers. CONCLUSIONS: Longer treatment duration and improved PROs were observed when advanced RCC patients managed targeted therapy-associated AEs well. Repeated education for consolidating AE self-management could be considered to enhance overall treatment outcomes.

Coexpression of lymphocyte-activation gene 3 and programmed death ligand-1 in tumor infiltrating immune cells predicts worse outcome in renal cell carcinoma.

OBJECTIVES: Lymphocyte-activation gene 3 (LAG-3) represents a potential immune checkpoint target for cancer treatment. We investigated LAG-3 expression and its prognostic value in patients with surgically treated clear cell renal cell carcinoma (RCC) and correlated LAG-3 expression with programmed cell death ligand 1(PD-L1). METHODS: We evaluated LAG-3 and PD-L1 expression using immunohistochemistry on tissue microarrays incorporating 134 primary excision specimens of clear cell RCC (ccRCC). The patients were analyzed as two groups: the whole cohort and those with metastatic RCC (mRCC). The cancer genome atlas (TCGA) data analysis of LAG-3 was done through UALCAN web servers. RESULTS: Using the UALCAN cancer transcriptional data analysis, we found that LAG-3 was overexpressed in ccRCC. LAG-3 expression was significantly correlated with PD-L1 expression in the whole cohort and in the mRCC group (all, p < 0.05). Both LAG-3⁺ RCC and PD-L1⁺ RCC presented with a higher TNM stage and higher Fuhrman nuclear grade (all, p < 0.05). PD-L1⁺/LAG-3⁺ RCC and PD-L1⁻/LAG-3⁺ RCC showed poorer cancer-specific survival (CSS) than PD-L1⁻/LAG-3⁻ RCC (all, p = 0.01). Similarly, PD-L1⁺/LAG-3⁺ mRCC and PD-L1⁻/LAG-3⁺ mRCC showed poorer CSS than PD-L1⁻/LAG-3⁻ mRCC (all, p < 0.05). Multivariate analysis showed that PD-L1⁺/LAG-3⁺ mRCC (hazard ratio: 3.19; 95% CI: 0.77-13.67; p = 0.033) was a predictor of poor CSS. CONCLUSION: Both LAG-3⁺ and PD-L1⁺ RCC have adverse pathological features, and their coexpression predicts worse clinical outcomes. Our findings suggest LAG-3 blockade in combination with programmed cell death 1/PD-L1 blockade as a potential therapeutic approach for RCC.

Association of serum prostate-specific antigen (PSA) level and circulating tumor cell-based PSA mRNA in prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) is used for diagnosing prostate cancer, but does not reflect the characteristics of prostate cancer cells to allow assessment of cancer progression. PSA mRNA and circulating tumor cells (CTCs) could be potential biomarkers. However, the relationship between serum PSA levels and PSA mRNA in CTCs is unclear, and this study aimed to investigate this relationship. METHODS: Healthy donors (HD, n = 9), and patients with local non-metastatic stage prostate cancer (n = 30), metastatic hormone-sensitive prostate cancer (mHSPC, n = 10), and metastatic castration-resistant prostate cancer (mCRPC, n = 75), were included. The expression of PSA mRNA in CTCs was measured by droplet digital PCR. Serum PSA (ng/mL) levels and PSA mRNA (copies/µL) in CTCs were then compared using Spearman correlation coefficients. RESULTS: PSA mRNA expression in CTCs was observed in 30% (9/30) of patients with localized cancer, 60.0% (6/10) among patients with mHSPC, 65.3% (49/75) among patients with mCRPC, and 0% among patients with HD, indicating that the detection rate of PSA mRNA increased with cancer stage. PSA mRNA expression in CTCs also increased from localized to metastatic stages. PSA mRNA levels rapidly increased in the mHSPC and mCRPC stages. Interestingly, PSA mRNA expression in CTCs was not correlated with serum PSA levels at the localized stage (R = 0.064, P = 0.512). However, there were significant correlations between serum PSA levels and PSA mRNA expression in mHSPC (R = 0.532, P = 0.041) and mCRPC (R = 0.566, P = 0.025). The number of CTCs isolated from mHSPC and mCRPC was not proportional to serum PSA and PSA mRNA levels. CONCLUSION: CTC PSA mRNA has the potential to be used as a biomarker to complement serum PSA protein analysis or replace serum PSA in metastatic stages of prostate cancer.

Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint molecule expressed in hematopoietic cells, granulocytes, macrophages, and monocytes. However, few studies to date have investigated VISTA expression, especially its clinical utility, in bladder cancer. The present retrospective study aimed to examine VISTA, programmed death ligand-1 (PD-L1), and CD45 expression by immunohistochemical and immunofluorescence staining of archived pathological tissue samples from 159 patients with primary bladder cancer. The correlation between VISTA expression in immune cells (ICs) and clinicopathologic variables including PD-L1 expression in ICs was examined. Briefly, the rates of VISTA-positive ICs and VISTA-positive tumor cells were 67.9% (108/159) and 30.8% (49/159), respectively. The VISTA expression in ICs of patients with bladder cancer, including those with non-muscle-invasive bladder cancer (NMIBC), was positively correlated with tumor stage, grade, size, and multiplicity. The VISTA expression in ICs was stronger in bladder cancer cases with PD-L1-positive ICs than in those with PD-L1-negative ICs (p < 0.001). The mean intravesical recurrence-free survival was shorter in NMIBC cases with VISTA-positive ICs than in those with VISTA-negative ICs (34.0 vs 39.9 months, p = 0.03, log-rank test). In this first study to investigate VISTA expression in bladder cancer, these results implicate VISTA as a potential immunotherapeutic target and immunologic biomarker in bladder cancer.

Prognostic significance of sarcopenia and decreased relative dose intensity during the initial two cycles of first-line sunitinib for metastatic renal cell carcinoma.

Targeted therapy for metastatic renal cell carcinoma (mRCC) treatment requires the identification of clinically important factors that can predict the therapeutic effect. We retrospectively investigated the prognostic roles of pre-treatment sarcopenia and relative dose intensity during the initial two cycles (2c-RDI) of sunitinib treatment in patients with mRCC. In total, 41 (52.6%) patients were classified as having sarcopenia and 16 (20.5%) patients were classified with low 2c-RDI at <75%. The mean dose reduction during sunitinib treatment was higher for sarcopenic than for non-sarcopenic patients. The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in sarcopenic patients with low 2c-RDI (n = 14, 17.9%) than in non-sarcopenic patients with high 2c-RDI (n = 35, 44.9%). Multivariate analysis identified sarcopenia and low 2c-RDI as poor prognostic factors for PFS and OS. Our findings provide new insights into the prognostic role of sarcopenia and 2c-RDI for targeted therapy in mRCC.

Trends in End-of-Life Resource Utilization and Costs among Prostate Cancer Patients from 2006 to 2015: A Nationwide Population-Based Study.

PURPOSE: The purpose of this study was to evaluate end-of-life resource utilization and costs for prostate cancer patients during the last year of life in Korea. MATERIALS AND METHODS: The study used the National Health Information Database (NHIS-2017-4-031) of the Korean National Health Insurance Service. Healthcare claim data for the years 2002 through 2015 were collected from the Korean National Health Insurance System. Among 83,173 prostate cancer patients, we enrolled 18,419 after excluding 1,082 who never claimed for the last year of life. RESULTS: From 2006 to 2015, there was a 3.2-fold increase the total number of prostate cancer decedents. The average cost of care during the last year of life increased over the 10-year period, from 14,420,000 Korean won to 20,300,000 Korean won, regardless of survival time. The cost of major treatments and medications, other than analgesics, was relatively high. Radiologic tests, opioids, pain control, and rehabilitation costs were relatively low. Multiple regression analysis identified age and living in rural area as negatively associated with prostate cancer care costs, whereas income level and a higher number of comorbidities were positively associated. CONCLUSIONS: Expenditure of prostate cancer care during the last year of life varied according to patient characteristics. Average costs increased every year. However, the results suggest underutilization of support services, likely due to lack of alternative accommodation for terminal prostate cancer patients. Further examination of patterns of utilization of healthcare resources will allow policymakers to take a better approach to reducing the burden of prostate cancer care.

Multigene model for predicting metastatic prostate cancer using circulating tumor cells by microfluidic magnetophoresis.

We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer-specific gene expressions were evaluated using mRNA from the isolated CTCs. A CTC-based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone-sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration-resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR-V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC-based genetic signatures may guide the early diagnosis of advanced prostate cancer.

Role of Prior Split Renal Function for Living Kidney Transplantation in Recipients and Donors.

PURPOSE: The purpose of this study was to determine the relationship between pre-operative donor split renal function (SRF) and the renal function outcome of donors and recipients after kidney transplantation (KT). METHODS: A total of 217 living KT cases were investigated. The estimated glomerular filtration rate (eGFR) change of recipients and donors, as well as graft survival, were analyzed based on the donor SRF. The difference in SRF (dSRF) in a donor was defined as follows: the SRF of the donated kidney minus the SRF of the remaining kidney determined by pre-operative 99mTc-diethylenetriaminepentaacetic acid in the donors. The dSRF was categorized into tertiles. RESULTS: The dSRF was not associated with the eGFR in recipients in any tertile at 6 or 12 months post-KT. The overall graft and patient survival did not differ significantly among tertiles. Donors in the high tertile, who donated kidneys with a higher SRF, showed a greater reduction in eGFR than did donors in the low and middle tertile after adjustment for function of the not-donated kidney (-34 ± 1.9 vs -28 ± 2.2, and -27 ± 1.3 mL/min/1.73 m2, P < .05). CONCLUSIONS: The dSRF did not affect the post-KT renal function or graft survival in recipients. However, the donors who donated the better functioning kidney had a poorer renal function after donation.

Effect of 5α-reductase inhibitors on the efficiency of thulium:yttrium-aluminium-garnet (RevoLix®) vaporesection for treating benign prostatic hyperplasia.

Purpose: Preoperative use of 5α-reductase inhibitors (5ARIs) may cause fibrosis of the prostate tissue and reduce the efficiency of thulium laser surgery for treating benign prostate hyperplasia (BPH). Thus, we investigated the effects of preoperative 5ARI use in this setting. Materials and Methods: This retrospective study examined 184 patients who underwent thulium laser surgery for BPH during 2012-2017. Patients were grouped according to their 5ARI use in order to compare their preoperative and intraoperative characteristics and subsequent outcomes. Surgical efficiency was assessed using vaporesection efficiency. The total operation time, vaporesection time and prostate volume change were measured. Results: The 5ARI+ group included 83 patients (45.1%) and the 5ARI- group included 101 patients (54.9%). There were no significant differences in the two groups' preoperative characteristics, postoperative prostate size, thulium laser energy use, or prostate volume reduction rate. However, relative to the 5ARI- group, the 5ARI+ group had a significant shorter total operative time (65.0 min vs. 70.0 min, p=0.013) and a significantly shorter vaporesection time (48.0 min vs. 54.0 min, p=0.014), which resulted in significantly higher vaporesection efficiency in the 5ARI+ group (0.66 mL/min vs. 0.51 mL/min, p<0.001). Both groups exhibit significant improvements in their quality of life score and International Prostate Symptom Score during the 12-month follow-up. Conclusions: In contrast with our expectations, the preoperative use of 5ARI increased the efficiency of thulium laser surgery for BPH. Thus, it may not be necessary to stop 5ARI treatment before performing thulium laser surgery in this setting.

National practice patterns and direct medical costs for prostate cancer in Korea across a 10 year period: a nationwide population-based study using a national health insurance database.

BACKGROUND: A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service. METHODS: Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated. RESULTS: From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter. CONCLUSIONS: Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.

Medical Travel among Non-Seoul Residents to Seek Prostate Cancer Treatment in Medical Facilities of Seoul.

PURPOSE: This study aims to investigate the trend in medical travel by non-Seoul residents to Seoul for treatment of prostate cancer and also to investigate the possible factors affecting the trend. MATERIALS AND METHODS: This study represents a retrospective cohort study using data from theKoreanNationalHealth Insurance System from 2002 to 2015. Annual trends were produced for proportions of patients who traveled according to the age group, economic status and types of treatment. Multiple logistic analysiswas used to determine factors affecting surgeries at medical facilities in Seoul among the non-Seoul residents. RESULTS: A total of 68,543 patients were defined as newly diagnosed prostate cancer cohorts from 2005 to 2014. The proportion of patients who traveled to Seoul for treatment, estimated from cases with prostate cancer-related claims, decreased slightly over 9 years (28.0 at 2005 and 27.0 at 2014, p=0.02). The average proportion of medical travelers seeking radical prostatectomy increased slightly but the increase was not statistically significant (43.1 at 2005 and 45.4 at 2014, p=0.26). Income level and performance ofrobot-assisted radical prostatectomy were significant positive factors for medical travel to medical facilities in Seoul. Combined comorbidity diseases and year undergoing surgery were significant negative factors for medical travel to medical facilities in Seoul. CONCLUSION: The general trend of patients travelling from outside Seoul for prostate cancer treatment decreased from 2005 to 2014. However, a large proportion of traveling remained irrespective of direct distance from Seoul.

Correlation between 5-α reductase type 2 protein expression and methylation of 5-α reductase type 2 promotor gene of benign prostatic hyperplasia.

PURPOSE: The enzyme 5-α reductase type 2 (5-AR 2) plays a key role in the development and maintenance of the prostate gland. We evaluated the level 5-AR 2 protein expression and the relationship between methylation of the 5-AR 2 gene-promoter and 5-AR 2 protein expression of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 37 prostate samples were evaluated. These included 22 samples from men undergoing transurethral prostate resections and 15 non-cancerous transition-zone human prostate tissue samples taken following radical prostatectomy. We quantified 5-AR 2 protein expression and gene-promoter methylation status using common assay procedures. Clinical variables included age, body mass index (BMI), prostate-specific antigen (PSA) levels, lipid profiles, and prostate volumes. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling. RESULTS: We were able to extract DNA from 36 of the 37 tissue samples and 10 of these (28%) did not express the 5-AR 2 protein. In total, 26 patients (72%) had methylated 5-AR 2 promoter-regions. There was a strong correlation between methylation of the 5-AR 2 promoter-regions and low-absent 5-AR 2 protein expression (p = 0.0003). Increasing age significantly predicted methylation status and protein expression level (p = 0.013). CONCLUSIONS: The level of 5-AR 2 protein expression varies among prostate tissue samples. Methylation of the 5-AR 2 gene-promoter may account for low or absent expression of 5-AR 2 in adult human prostate tissues. Increased age correlates with increased 5-AR 2 gene-promoter methylation and decreased protein expression in men with BPH.

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.

Efficacy and safety of tamsulosin 0.4 mg single pills for treatment of Asian patients with symptomatic benign prostatic hyperplasia with lower urinary tract symptoms: a randomized, double-blind, phase 3 trial.

OBJECTIVE: To verify the efficacy and safety of tamsulosin 0.4 mg and tamsulosin 0.2 mg compared with those of placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). METHODS: A total of 494 patients from multiple centers participated in this double-blind, randomized, phase 3 trial. Eligible patients were randomly assigned to the tamsulosin 0.4 mg group, tamsulosin 0.2 mg group or placebo group. The International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual (PVR) urine volume, blood pressure, heart rate and adverse events were compared among the three groups at 4, 8 and 12 weeks. RESULTS: A total of 494 BPH patients were analyzed. There were no differences in the baseline characteristics among the three groups. After 12 weeks of treatment, total IPSS was improved in the 0.2 mg and 0.4 mg tamsulosin groups; however, the extent of improvement was greater in the 0.4 mg group than in the 0.2 mg group (0.4 mg: -9.59 vs. 0.2 mg: -5.61; least-squares mean difference [95% confidence interval]: -3.95 [-5.01, -2.89], p < .0001). In addition, in the patients with severe symptoms (IPSS ≥20), total IPSS was improved the most in the 0.4 mg group (-11.27 ± 5.00, p < .0001). Qmax and PVR were improved in the 0.4 mg and 0.2 mg groups; however, the differences were not statistically significant between treatment groups. No patients experienced any serious adverse effects in any of the three groups. CONCLUSIONS: Tamsulosin 0.4 mg and 0.2 mg appear to be superior to placebo treatment, and tamsulosin 0.4 mg is more effective than 0.2 mg in terms of total IPSS improvement. Tamsulosin 0.4 mg has favorable efficacy and tolerability in Asian men with symptomatic BPH. ClinicalTrials.gov Identifier: NCT02390882.

Factors Associated with Rebleeding in Patients with Peptic Ulcer Bleeding: Analysis of the Korean Peptic Ulcer Bleeding (K-PUB) Study.

BACKGROUND/AIMS: Rebleeding is associated with mortality in patients with peptic ulcer bleeding (PUB), and risk stratification is important for the management of these patients. The purpose of our study was to examine the risk factors associated with rebleeding in patients with PUB. METHODS: The Korean Peptic Ulcer Bleeding registry is a large prospectively collected database of patients with PUB who were hospitalized between 2014 and 2015 at 28 medical centers in Korea. We examined the basic characteristics and clinical outcomes of patients in this registry. Univariate and multivariate analyses were performed to identify the factors associated with rebleeding. RESULTS: In total, 904 patients with PUB were registered, and 897 patients were analyzed. Rebleeding occurred in 7.1% of the patients (64), and the 30-day mortality was 1.0% (nine patients). According to the multivariate analysis, the risk factors for rebleeding were the presence of co-morbidities, use of multiple drugs, albumin levels, and hematemesis/hematochezia as initial presentations. CONCLUSIONS: The presence of co-morbidities, use of multiple drugs, albumin levels, and initial presentations with hematemesis/hematochezia can be indicators of rebleeding in patients with PUB. The wide use of proton pump inhibitors and prompt endoscopic interventions may explain the low incidence of rebleeding and low mortality rates in Korea.

Comparison of the Effect of Naftopidil 75 mg and Tamsulosin 0.2 mg on the Bladder Storage Symptom With Benign Prostatic Hyperplasia: Prospective, Multi-institutional Study.

OBJECTIVE: To compare the efficacies of naftopidil and tamsulosin in terms of reducing storage symptoms in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: This prospective randomized study was performed at 10 centers. Ninety-four patients that had been taking tamsulosin for more than 8 weeks, but had an Overactive Bladder Symptom Score (OABSS) of greater than 3 points, were initially enrolled. After a 1-week washout period, patients were divided into 2 groups. Forty-five patients were treated with tamsulosin 0.2 mg daily, and 49 patients were treated with naftopidil 75 mg daily for 8 weeks. Total International Prostate Symptoms Score (IPSS), storage symptom scores, nocturia times, OABSS, maximal flow rates (Qmax), and postvoid residual volumes were checked before and after the 8-week treatment period. RESULTS: Mean patient ages in the tamsulosin and naftopidil groups were 64.8 and 66.0 years, respectively. Baseline characteristics were not significantly different. In the tamsulosin group, mean total IPSS decreased from 19.1 to 15.1 after the 8-week treated period (P = .001), and in the naftopidil group, mean total IPSS decreased from 16.9 to 13.1 (P = .001). Mean storage symptom scores were reduced in the tamsulosin and naftopidil groups from 8.0 to 6.6 (P = .002) and from 7.6 to 6.1 (P = .001), respectively. Mean nocturia times in the naftopidil groups decreased significantly from 2.5 to 1.9 (P = .001), and mean OABSSs were reduced from 7.7 to 6.0 (P = .001) and from 7.4 to 6.0 (P = .001), respectively. CONCLUSION: Total IPSS, storage symptom scores, nocturia times, and OABSS were significantly reduced by naftopidil and tamsulosin. Moreover, the naftopidil group showed better improvements in nocturia than the tamsulosin group.

Correlation between postoperative prostate-specific antigen and biochemical recurrence in positive surgical margin patients: Single surgeon series.

BACKGROUND: To evaluate the relationship between postoperative prostate-specific antigen (PSA) levels and biochemical recurrence (BCR) after radical prostatectomy, especially in patients with positive surgical margins (PSMs). MATERIALS AND METHODS: A total of 144 patients who underwent radical prostatectomies performed by a single surgeon without any neoadjuvant or adjuvant treatment were analyzed. Differences in clinicopathological factors were compared by surgical margin status, and the relationship between postoperative PSA level and BCR in patients with PSMs was evaluated. RESULTS: Fifty of the 144 patients (34.7%) had PSMs. Of these, 74% experienced BCR. The negative surgical margins and PSMs groups differed significantly in terms of PSA level at diagnosis, clinical T stage, and risk group by the cancer of the prostate risk assessment score (P = 0.002, P = 0.002, and P = 0.004, respectively). Also, the nadir PSA level, tumor volume, and BCR rate differed between the two groups (P = 0.007, P = 0.015, and P = 0.005, respectively) On Kaplan-Meier analysis, BCR-free survival was better in the negative surgical margins than the PSMs group (64.1 vs. 55.4 months, log-rank test, P = 0.011). BCR-free survival did not differ significantly in PSMs patients according to whether PSA level was or was not detectable at 1 month postoperatively. However, BCR-free survival improved when the nadir PSA level was undetectable (compared to detectable) in PSMs patients (64.3 vs. 26.1 months, log-rank test, P < 0.001). In PSMs patients belonging to the high risk group by cancer of the prostate risk assessment score, BCR-free survival was significantly better when the PSA level attained the nadir within 3 months, compared to > 6 months, postoperatively (64.2 vs. 29.5 months, log-rank test, P = 0.022). CONCLUSION: If PSA is detectable in PSMs patients until 1 month after operation, cautious observation may be possible. If the nadir is attained within 3 months postoperatively in high-risk patients with PSMs, better BCR-free survival may be expected.

Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP.

Aberrant up-regulation of Wnt/ß-catenin signaling is associated with the development and progression of prostate cancer, but the underlying mechanism is unclear. Here we show that in the absence of androgens, the Wnt/ß-catenin pathway activates AR-mediated transcription through up-regulation of the Hippo pathway effector Yes-associated protein (YAP). Wnt3a-conditioned medium (Wnt3a-CM) promotes the growth of LNCaP cells and increases AR and YAP protein levels. Moreover, Wnt3a-CM induces the nuclear translocation of YAP and the AR, but not ß-catenin, thereby activating the expression of AR- and YAP-dependent genes, in an androgen-independent manner. In addition, depletion of YAP with small interfering RNA (siRNA) prevented Wnt3a-CM-mediated up-regulation of AR-dependent gene expression. Thus, our findings provide mechanistic insight into the proposed cross-talk between the Wnt/ß-catenin and Hippo pathways in androgen-independent prostate cancer development.