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Abstract. Background. Only a few reports have currently studied the efficacy of dutasteride in patients with small benign prostatic hyperplasia (BPH). We investigated the efficacy of dutasteride on reducing lower urinary tract symptoms among them. Materials and methods. A total of 81 patients with BPH who completed 52weeks of 0.5?mg dutasteride treatment were enrolled. Each patient filled out the International Prostatic Symptom Score (IPSS) and overactive bladder symptom score (OABSS) at baseline and at the 6- and 12-month follow-up visits. Total testosterone, prostate-specific antigen, adenoma/prostate volume (PV), uroflowmetry analysis, and postvoid residual volume were evaluated at baseline and at the 12-month follow-up visit. The enrolled patients were divided into 2 groups according to PV at baseline. The groups were as follows: Group A (PV ≥ 30 mL) and Group B (PV < 30 mL). Results. Groups A and B had mean PVs of 52.1 and 23.6 mL and mean IPSS scores of 16.7 and 14.4, respectively. Group A had significantly higher OABSS and prostate-specific antigen levels at baseline than Group B, while no significant differences in any other baseline characteristics was observed. After dutasteride treatment, adenoma volume and PV decreased significantly, while testosterone level showed a significant increase in both groups. Group A showed significant improvements in the total IPSS, voiding and storage subscore of the IPSS, OABSS, maximum flow rate, and postvoid residual volume. Group B, on the other hand, also showed significant improvements only in the total IPSS, voiding subscore of the IPSS, and maximum flow rate. Conclusions. The present study suggests a possible beneficial effect of dutasteride treatment on the reduction of lower urinary tract symptoms in patients with small and large BPH. However, the effectiveness of dutasteride was limited compared to patients with large BPH (PV ≥ 30 mL).

Abstract Background In the global ARASENS study (NCT02799602), darolutamide plus androgen‐deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57–0.80; p

Introduction Low‐dose‐rate brachytherapy is performed for localized prostate cancer. We report the first case of a bladder stone encompassing the seed migrated into the bladder in a patient treated with low‐dose‐rate brachytherapy. Case presentation A man was diagnosed with prostate cancer and underwent low‐dose‐rate brachytherapy. After 2 months, dysuria occurred, and ultrasonography revealed a needle‐shaped high‐intensity protruding from the prostate into the bladder. Cystoscopy examination found a seed link connector. With the possibility of natural dissolution of the seed link, careful observation was chosen. However, 16 months later, hematuria occurred, and an X‐ray revealed a bladder stone encompassing the seed. Compared with the X‐ray right after seeding, the seed located near the right bladder neck had fallen. The seed was removed by transurethral bladder lithotripsy. Conclusion Seeds should be carefully located within the prostate, otherwise a bladder stone may be formed encompassing the seed.

Abstract Background The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. Methods This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. Discussion This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358

Purpose: In irradiating the prostate and pelvic lymph node regions, registration based on bony structures matches the pelvic lymph node regions but not necessarily the prostate position, and it is important to identify factors that influence prostate displacement. Therefore, we investigated factors influencing prostate displacement during volumetric modulated arc therapy after single-fraction high-dose-rate brachytherapy (HDR-BT) for prostate cancer and the trends in displacement for each fraction. Methods and Materials: Seventy patients who underwent pelvic volumetric modulated arc therapy of 46 Gy in the prone position 15 days after 13 Gy HDR-BT were included. Prostate displacement relative to bony structures was calculated using cone beam computed tomography. Systematic error (SE) and random error (RE) were evaluated in the right-left (RL), craniocaudal (CC), and anteroposterior (AP) directions. The association with clinical and anatomic factors on the planning computed tomography or magnetic resonance imaging was analyzed. Prostate volume change (PVC) was defined as the volume change at 2 days after HDR-BT. Displacement trends were individually examined from the first to 23rd fractions. Results: The mean SE in the RL, CC, and AP directions was –0.01 mm, –2.34 mm, and –0.47 mm, respectively. The root mean square of the RE in the RL, CC, and AP directions was 0.44 mm, 1.14 mm, and 1.10 mm, respectively. SE in the CC direction was independently associated with bladder volume (P = .021, t statistic = 2.352) and PVC (P < .001, t statistic = –8.526). SE in the AP direction was independently associated with bladder volume (P = .013, t statistic = –2.553), PVC (P < .001, t statistic = 5.477), and rectal mean area (P = .008, t statistic = 2.743). RE in the CC direction was independently associated with smoking (P = .035). RE in the AP direction was associated with PVC (P = .043). Gradual displacement caudally and posteriorly occurred during the irradiation period. Conclusions: Anatomic characteristics of the bladder, rectum, and prostate predict SE. Smoking and PVC predict RE. In particular, whether PVC is ≥140% affects setting internal margins.

Abstract Retzius-sparing robot-assisted radical prostatectomy (RARP) has been reported to exhibit better postoperative urinary continence, but the reasons behind this are unknown. This study included 254 cases who underwent RARP and underwent postoperative dynamic MRI. We measured the urine loss ratio (ULR) immediately after postoperative urethral catheter removal and investigated its affecting factors and the mechanisms. Nerve-sparing (NS) techniques was performed in 175 (69%) unilateral and 34 (13%) bilateral cases, whereas Retzius-sparing in 58 (23%) cases. The median ULR early after indwelling catheter removal in all patients was 4.0%. The multivariate analysis was performed on factors that reduce ULR and found that the following factors were associated with ULR: younger age, NS and Retzius-sparing, which were significant. Additionally, dynamic MRI findings showed that membranous urethral length and the anterior rectal wall movement toward the pubic bone during abdominal pressure were significant factors. The movement observed on the dynamic MRI during abdominal pressure was thought to reflect an effective urethral sphincter closure mechanism. Long membranous urethral length and an effective urethral sphincter closure mechanism during abdominal pressure were considered effective for favorable urinary continence after RARP. NS and Retzius-sparing were clearly shown to have an additive effect in preventing urinary incontinence.

Aim: This study investigated the relationship between erectile dysfunction (ED) and adiponectin levels in hypogonadal men.Methods: In this study, 218 patients with hypogonadism (mean age: 65.1 ± 8.3 years) were enrolled. All patients underwent physical examinations, with measurement of body mass index, body fat ratio, and waist circumference. The erectile function was assessed using the sexual health inventory for men (SHIM) scoring system. Blood biochemical profiles such as free testosterone, fasting blood glucose, and lipid profile including adiponectin levels were measured. All patients were divided into two groups based on their SHIM score: normal to moderate ED (SHIM score ≥ 12) and severe ED (SHIM score < 12), and the factors associated with severe ED were determined. Patients with severe ED were divided into two groups based on adiponectin levels (cutoff value of 7.0 μg/mL), and their basic characteristics were compared between these two groups.Results: The severe ED group was older and had higher adiponectin levels. In patients with severe ED, various metabolic parameters were significantly worse in the low adiponectin groups than in the non-low adiponectin group.Conclusions: The risk of developing cardiovascular diseases is extremely high in hypogonadal men with severe ED who had lower serum adiponectin levels.

Introduction One of the complications of laparoscopic surgery is gas embolism, which has low incidence but high mortality. Carbon dioxide embolism diagnosed during robot‐assisted laparoscopic partial nephrectomy has been experienced. Case presentation 77‐year‐old woman with a left renal tumor received robot‐assisted laparoscopic partial nephrectomy. End‐tidal carbon dioxide pressure and oxygen saturation of peripheral artery suddenly decreased 5 min after the start of tumor resection with pneumoperitoneum pressure of 15 mmHg and positive end‐expiratory pressure turned off. Therefore, pulmonary artery gas embolism was diagnosed. The pneumoperitoneum pressure was dropped, and positive end‐expiratory pressure was restarted. These conditions improved and the procedure was completed. Conclusion Carbon dioxide gas embolism during robot‐assisted partial nephrectomy should be focused on because prompt diagnosis and treatment will improve life outcomes. The optimal pneumoperitoneum pressure for each case, rather than making it uniform, should be reconsidered.

Abstract Background and Aims Testosterone deficiency is often related to geriatric syndrome including erectile dysfunction, osteo‐porosis, depression, cognitive impairment, cardiovascular diseases and frailty. Despite the existence of many studies on short‐term exercise and serum testosterone levels, few research have focused on exercise habits from young age and testosterone values in middle‐aged male. In this study, we investigated whether belonging to an athletic club from school age could predict serum‐free testosterone (FT) levels. Methods The subjects were 1609 middle‐aged male outpatients aged 40 years or older (median: 61 years, interquartile range: 54–69) who visited our hospital. Participants had their FT values measured in the morning hours during the period from December 2007 to June 2009. A questionnaire survey on exercise habits was conducted at the same time as the measurements. The exercise habit questionnaire was created based on whether the patients belonged to an athletic club in (a) elementary school, (b) junior high school, (c) high school, (d) college, (e) adult life, and (f) at the time of the test. Results There was only one positive response to the questionnaire among 456 patients (28% of total), followed by zero for 358 patients (22% of total). The number of patients with low‐testosterone levels (FT

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan–Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

Introduction Recently, an absorbable hydrogel spacer is becoming more widespread to reduce rectal radiation dose for radiation therapy for localized prostate cancer. Case presentation A 79‐year‐old male patient was referred to our hospital for radical treatment of organ‐confined prostate cancer. Low‐dose‐rate brachytherapy was performed, and the hydrogel spacer injection was added. The spacer was properly injected between the prostate and the rectum, causing no acute complications during hospitalization. Two months after low‐dose‐rate brachytherapy, the patient visited our hospital with constipation and melena, without fever. He was diagnosed with ischemic proctitis based on clinical courses and examinations. He was hospitalized for 19 days and made a complete recovery with conservative treatment. Conclusions Herein, we report the first case of ischemic proctitis after low‐dose‐rate brachytherapy using hydrogel spacer for prostate cancer.

Background: Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) improve survival in castration-resistant prostate cancer (CRPC). However, which agent is better for patients with CRPC remains unclear. Objective: To evaluate whether ENZ or ABI is better as first-line treatment for CRPC. Design, setting, and participants: An investigator-initiated, multicenter, randomized controlled trial was conducted in Japan. The study enrolled 203 patients with CRPC before chemotherapy between February 20, 2015, and July 31, 2019. Patients were randomly assigned 1:1 to the ENZ or ABI arm. Outcome measurements and statistical analysis: The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included the PSA response rate (≥50% decline from baseline), overall survival, and safety. A log-rank test was used for comparison of survival analyses between arms. Results and limitations: After randomization, 92 patients in each arm were treated and analyzed. Time to PSA progression did not significantly differ between the arms (median 21.2 mo for ENZ and 11.9 mo for ABI; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.51–1.27; p = 0.1732). There was a significant difference in the PSA response rate between the arms (72% for ENZ and 57% for ABI; p = 0.0425). There was no significant difference in overall survival (median 32.9 mo for ENZA and 35.5 mo for ABI; HR 1.17, 95% CI 0.72–1.88; p = 0.5290). Grade ≥3 adverse events were observed in 11% of patients in the ENZA arm and 21% in the ABI arm (p = 0.1044). Conclusions: ENZ did not show any survival benefit in comparison to ABI, but showed a better PSA response rate with a low rate of severe adverse events in CRPC. Patient summary: Results from our study suggest that use of enzalutamide before abiraterone may have potential clinical benefits for patients with castration-resistant prostate cancer.

Abstract Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) exhibits better postoperative urinary continence than conventional RARP (C-RARP) via the anterior approach. However, the reasons behind this are unknown. Herein, early postoperative urinary incontinence and anatomical differences of 51 propensity score-matched C-RARP and RS-RARP cases were compared. Dynamic magnetic resonance imaging (MRI) was performed before and after surgery to examine the pelvic anatomical changes under abdominal pressure. The median urine loss ratios in the early postoperative period after C-RARP and RS-RARP were 11.0% and 1.0%, respectively. Postoperative MRI revealed that the anterior bladder wall was fixed in a higher position after RS-RARP compared with its position after C-RARP. Dynamic MRI after C-RARP showed that cephalocaudal compression of the bladder while applying abdominal pressure caused the membranous urethra to expand and the urine to flow out. After RS-RARP, the rectum moved forward during abdominal pressure, and the membranous urethra was compressed by closure from behind. This is the first study using dynamic MRI to reveal the importance of high attachment of the anterior bladder wall for the urethral closure mechanism during abdominal pressure. RS-RARP, which can completely preserve this mechanism, is less likely to cause stress urinary incontinence compared with C-RARP.

Abstract Entering a drug‐tolerant persister (DTP) state of cancer cells is a transient self‐adaptive mechanism by which a residual cell subpopulation accelerates tumor progression. Here, we identified the acquisition of a DTP phenotype in multidrug‐resistant (MDR) cancer cells as a tolerance response to routine combination treatment. Characterization of MDR cancer cells with a DTP state by RNA‐seq revealed that these cells partially prevented chemotherapy‐triggered oxidative stress by promoting NPC1L1‐regulated uptake of vitamin E. Treatment with the NPC1L1 inhibitor ezetimibe further enhanced the therapeutic effect of combinatorial therapy by inducing methuosis. Mechanistically, we demonstrated that NRF2 was involved in transcriptional regulation of NPC1L1 by binding to the −205 to −215 bp site on its promoter. Decreased DNA methylation was also related partially to this process. Furthermore, we confirmed that a triple‐combination of chemotherapeutic agents, verapamil, and ezetimibe, had a significant anti‐tumor effect and prevented tumor recurrence in mice. Together, our study provides a novel insight into the role of DTP state and emphasizes the importance of disrupting redox homeostasis during cancer therapy.

Abstract Background Overcoming drug resistance is critical for increasing the survival rate of prostate cancer (PCa). Docetaxel is the first cytotoxic chemotherapeutical approved for treatment of PCa. However, 99% of PCa patients will develop resistance to docetaxel within 3 years. Understanding how resistance arises is important to increasing PCa survival. Methods In this study, we modeled docetaxel resistance using two PCa cell lines: DU145 and PC3. Using the Passing Attributes between Networks for Data Assimilation (PANDA) method to model transcription factor (TF) activity networks in both sensitive and resistant variants of the two cell lines. We identified edges and nodes shared by both PCa cell lines that composed a shared TF network that modeled changes which occur during acquisition of docetaxel resistance in PCa. We subjected the shared TF network to connectivity map analysis (CMAP) to identify potential drugs that could disrupt the resistant networks. We validated the candidate drug in combination with docetaxel to treat docetaxel-resistant PCa in both in vitro and in vivo models. Results In the final shared TF network, 10 TF nodes were identified as the main nodes for the development of docetaxel resistance. CMAP analysis of the shared TF network identified trichostatin A (TSA) as a candidate adjuvant to reverse docetaxel resistance. In cell lines, the addition of TSA to docetaxel enhanced cytotoxicity of docetaxel resistant PCa cells with an associated reduction of the IC50 of docetaxel on the resistant cells. In the PCa mouse model, combination of TSA and docetaxel reduced tumor growth and final weight greater than either drug alone or vehicle. Conclusions We identified a shared TF activity network that drives docetaxel resistance in PCa. We also demonstrated a novel combination therapy to overcome this resistance. This study highlights the usage of novel application of single cell RNA-sequencing and subsequent network analyses that can reveal novel insights which have the potential to improve clinical outcomes.

Abstract Background To investigate risk factors for orally administered 5-aminolevulinic acid (ALA)-induced hypotension for bladder cancer patients receiving photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT). Methods Patients were categorized into two groups intraoperatively: a hypotensive group (minimum systolic blood pressure (SBP) ≤80 mmHg) and a non-hypotensive group (minimum SBP > 80 mmHg). We examined differences between the hypotensive group and non-hypotensive groups to identify clinical risk of ALA-induced hypotension using multivariate logistic regression analysis and decision tree analysis. Results Among 282 cases with ALA-PDD-assisted TURBT from three institutions who were screened, 245 patients were included in the final analysis. In total, 156 patients (63.7%) showed any grade of hypotension during ALA-PDD-assisted TURBT. General anesthesia and spinal anesthesia were induced intraoperatively in 113 patients (46.1%) and 132 patients (53.9%), respectively. Median SBP at baseline (before taking ALA) and at the beginning of anesthesia was 127 mmHg (range, 69–186 mmHg) and 124 mmHg (range, 69–186 mmHg), respectively. Median minimum SBP during ALA-PDD-assisted TURBT was 75 mmHg (range, 43–140 mmHg). Multivariate logistic regression analysis revealed that history of hypertension (odds ratio (OR) 7.568, p

Abstract Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.

ABSTRACT: Objectives: The effects of human papillomavirus (HPV) infection on male reproductive parameters are currently a matter of controversy. In order to clarify the issue in Japanese infertile men, the prevalence and localization of HPV in semen, sperm parameters, and superoxide dismutase (SOD) activity in seminal plasma were examined in 216 Japanese infertile men. Methods: DNA was extracted from liquid-based cytological semen samples. The β-globin gene was amplified by polymerase chain reaction (PCR), and HPV-DNA was amplified using nested PCR with MY09/MY11 as outer primers and GP5+/GP6+ as inner primers. HPV genotyping was performed in the HPV-positive samples. In addition, SOD levels in seminal plasma were analysed quantitatively. In-situ hybridization (ISH) was performed to localize HPV-DNA in sperm from HPV-positive samples. Results: Any-risk and high-risk prevalence rates of HPV in semen were 12.5% and 6.9%, respectively. No significant difference in the prevalence of HPV was observed between azoospermic and non-azoospermic subjects. Among non-azoospermic patients, those with HPV detected in semen had significantly lower sperm motility and concentration compared with subjects without HPV detected in semen. SOD levels in seminal plasma were significantly higher in HPV-positive patients compared with HPV-negative patients. ISH analysis of HPV-positive samples revealed that HPV-DNA was localized to the head and mid-piece of sperm. HPV-DNA was present in the sperm of young infertile men. Conclusion: HPV infection of sperm was associated with reduced sperm motility and concentration, and resulted in an increase in seminal SOD activity.

Abstract Background Due to the development of novel equipment for the acquisition of two‐dimensional serial images and software capable of displaying three‐dimensional (3D) images from serial images, the accurate 3D reconstruction of organs and tissues has become possible. Methods Based on published studies, this review summarizes techniques for the 3D reconstruction of the testis cords/seminiferous tubules, with special reference to our method using serial paraffin sections and 3D visualization software. Main findings The testes of mice, rats, and hamsters of various ages were 3D reconstructed and species and age differences in the structures of the testis cords/seminiferous tubules were analyzed. Our method is advantageous because conventional paraffin‐embedded normal and pathological specimens may be utilized for the 3D analysis without the need for complicated and expensive equipment. Conclusion By further decreasing the time and labor required for the procedure and adding information on molecular localization, the technique for 3D reconstruction will contribute to the elucidation of not only the structures, but also the functions of various organs, including the testis.

BackgroundThe detection of microsatellite instability in urologic cancers is rare, especially in metastatic, castration-resistant prostate cancer with neuroendocrine differentiation.Case presentationThis is a case of a 66-year-old Asian male patient with prostate adenocarcinoma who had metastases at initial presentation. Despite combined androgen deprivation therapy, his prostate-specific antigen (PSA) progressively increased, and prostate re-biopsy revealed small cell carcinoma. He was treated with platinum-based systemic chemotherapy, and his tumor markers, including PSA, remained negative; however, his local symptoms worsened. Subsequently, microsatellite instability-high was detected, and pembrolizumab was administered resulting in complete remission with the resolution of symptoms and continued therapeutic effect for more than 14 months.ConclusionMicrosatellite instability testing should be considered, despite its low detection rate, because the response to pembrolizumab in metastatic, castration-resistant prostate cancer with detectable microsatellite instability is associated with a prolonged duration of response.

Purpose: The purpose of this study is to observe how preoperative sarcopenia and hypoalbuminemia affect the oncological outcome of nonmetastatic renal cell carcinoma (RCC) after partial or radical nephrectomy. Methods: This study retrospectively analyzes 288 Japanese patients with nonmetastatic RCC who underwent radical treatment at Kanazawa University Hospital between October 2007 and December 2018. Relationships between sarcopenia as indicated by the psoas muscle mass index and hypoalbuminemia (albumin ≤ 3.5 g/dL) with overall survival (OS) and metastasis-free survival (MFS) were determined. Results: The study found that 110 (38.2%) of the 288 patients were sarcopenic and 29 (10.1%) had hypoalbuminemia. The combination of sarcopenia and hypoalbuminemia was associated with a shorter OS and MFS (p for trend = 0.0007 and p = 0.041) and poor OS (HR, 6.87; 95% CI, 1.75–26.94; p = 0.006), respectively. Conclusions: In Japanese patients with surgically treated nonmetastatic RCC, combined preoperative sarcopenia and hypoalbuminemia was a significant predictor of poor survival.

Abstract Background Hypogonadism associated with cancer is reported to cause cachexia and a variety of physical and psychological symptoms. This study aims to evaluate whether androgen replacement therapy can improve cancer‐related symptoms in male advanced cancer patients. Methods An investigator‐initiated, prospective, and randomized controlled study was conducted. Patients with low serum testosterone levels (total or free testosterone levels were

Abstract Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P

A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of ≥ 7 and 273 had a GS of 24, PSA density ≥ 0.24 ng ml−2, positive findings on digital rectal examination, and transrectal with 90.0% sensitivity and 67.4% specificity. In this study, we found that raising the PSA cutoff to 12 ng ml−1 for CSPC in elderly individuals can significantly reduce unnecessary prostate biopsies. Furthermore, CSPC could be efficiently discovered by combining the four supplementary markers in patients with a PSA level of 4–12 ng ml−1. By performing this screening for elderly men over 75 years of age, unnecessary biopsies may be reduced and CSPC may be detected efficiently.

Abstract Despite improvements in systemic therapy options for renal cancer, it remains one of the most drug-resistant malignancies. Interestingly, reports have shown that kahweol and cafestol, natural diterpenes extracted from coffee beans, exhibit anti-cancer activity. However, the multiple potential pharmacological actions of both have yet to be fully understood. This study therefore investigated the effects of kahweol acetate and cafestol on human renal cancer ACHN and Caki-1 cells. Accordingly, the combination of kahweol acetate and cafestol administration synergistically inhibited cell proliferation and migration by inducing apoptosis and inhibiting epithelial–mesenchymal transition. Mechanistic dissection revealed that kahweol acetate and cafestol inhibited Akt and ERK phosphorylation. Moreover, kahweol acetate and cafestol downregulated the expression of not only C–C chemokine receptors 2, 5, and 6 but also programmed death-ligand 1, indicating their effects on the tumor microenvironment. Thus, kahweol acetate and cafestol may be novel therapeutic candidates for renal cancer considering that they exert multiple pharmacological effects.

The azoospermia factor (AZF) region is important for spermatogenesis, and deletions within these regions are a common cause of oligozoospermia and azoospermia. Although several studies have reported this cause, the present research, to the best of our knowledge, is the first large-scale study assessing this factor in Japan. In this study, 1030 male patients with infertility who were examined for Y chromosome microdeletion using the polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) method, a newly developed method for Y chromosome microdeletion screening, were included. The study enrolled 250 patients with severe oligospermia and 717 patients with azoospermia. Among the 1030 patients, 4, 4, 10, and 52 had AZFa, AZFb, AZFb+c, and AZFc deletions, respectively. The sperm recovery rate (SRR) of microdissection testicular sperm extraction in patients with AZFc deletions was significantly higher than that in those without AZF deletions (60.0% vs 28.7%, P = 0.04). In patients with gr/gr deletion, SRR was 18.7%, which was lower than that in those without gr/gr deletion, but was not statistically significant. In conclusion, our study showed that the frequency of Y chromosome microdeletion in male patients in Japan was similar to that reported in patients from other countries, and SRR was higher in patients with AZFc deletion.

We had six cases of patients who were treated with long-term testosterone replacement therapy (TRT) after high dose-rate (HDR) brachytherapy and androgen deprivation therapy for high-risk prostate cancer. All patients were given testosterone enanthate by intramuscular injection every 3 to 4 weeks. Blood biochemistry including prostate specific antigen (PSA) level was evaluated every 3 to 6 months after TRT, and radiological imaging was performed every 12 months. All patients had slight increases in PSA within the normal range and not indicative of biochemical recurrence. A sudden increase in PSA was observed in one patient, but it finally decreased. Aging male symptoms scale and various metabolic factors were improved by TRT in all of cases. Although adverse events included polycythemia in one patient, no patients experienced disease recurrence or progression during TRT. Our results suggest TRT for high risk-patients with HDR brachytherapy for prostate cancer may be beneficial and safe.

It has been reported that chemotherapy drugs and granulocyte colony-stimulating factor (G-CSF) administered on the same day can aggravate neutropenia. In the present study, we investigated the safety of pegfilgrastim during bleomycin, etoposide, and cisplatin (BEP) therapy. This single-center retrospective study, including 137 cycles of BEP therapy for germ cell tumors between January 2008 and April 2021, investigated safety. Short-acting G-CSF was used for 84 cycles and pegfilgrastim was used for 53 cycles. In the pegfilgrastim group, neutrophil count at nadir was significantly higher than in the G-CSF group (median 1,650/μl and 680/μl, respectively). The incidence of grade 3–4 neutropenia was significantly higher and the duration longer in the G-CSF group. Also, there was no significant difference in the incidence of febrile neutropenia. In conclusion, concomitant use of pegfilgrastim during BEP therapy did not increase neutropenia and was effective in terms of safety.

Several markers that reflect inflammation and nutritional status have been associated with oncological outcomes in many tumors. This study aimed to describe the impact of pretreatment inflammatory and nutritional indices on the oncological outcomes in nonmetastatic renal cell carcinoma (RCC). A total of 213 Japanese patients with nonmetastatic RCC at Kanazawa University Hospital between October 2007 and December 2018 were included. The inflammatory and nutritional indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), were retrospectively analyzed. The optimal cutoffs for NLR, PLR, CAR, PNI, and GNRI were 2.18, 153.7, 0.025, 48.4, and 98, respectively. According to Kaplan–Meier curves, elevated NLR, PLR, CAR, and GNRI correlated with increased metastasis, while NLR and PNI correlated with worse overall survival (OS). In multivariate analysis, high CAR was an independent poor risk factor for metastasis (hazard ratio (HR), 3.08; 95% confidence interval (CI), 1.24–7.67; p = 0.016). Furthermore, high NLR showed an independent prognostic factor for worse OS (HR, 3.96; 95% CI, 1.01–15.59; p = 0.049). The pretreatment inflammatory and nutritional indices such as NLR and CAR might be promising prognostic factors for nonmetastatic RCC.

ABSTRACT: Introduction: Decreased libido in middle-aged and elderly men is often difficult to treat, and identifying the risk factors affecting decreased libido is important for the clinical management of decreased libido. However, limited information is available regarding specific risk factors in this population. Aim: The present study investigated the risk factors for decreased libido among middle-aged and elderly men. Methods: Patients who attended our male andropausal outpatient clinic between 2009 and 2015 were enrolled. All patients completed a self-administered questionnaire, which included the Aging Male Symptoms (AMS) scale, International Prostate Symptom Score (IPSS), and Sexual Health Inventory for Men (SHIM). Information on waist size, body mass index, present illness, present use of any medication, and lifestyle habits were collected by each attending physician. Blood biochemical data such as free testosterone, total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-Chol), and hemoglobin A1c values were assessed. Libido was assessed based on AMS scale question 17, and a score of 4 or higher was defined as severely decreased libido (severe group). Main Outcome Measure: The clinical factors associated with severely decreased libido were analyzed based on multiple regression analysis. Results: A total of 292 subjects were included in the analysis, 111 (38%) of which belonged to the severe group. The mean age of study subjects was 66.2 years, and the mean FT value was 7.1 ± 2.2. Comparisons of each variable among the severe and not severe groups showed significant differences in older age, current cigarette smoking, AMS scale, IPSS, frequency of nocturnal voiding, SHIM score, and HDL-Chol value. Multivariate regression analysis revealed that current cigarette smoking, frequent nocturnal voiding, and a low SHIM score were the independent risk factors for severely decreased libido. Furthermore, the frequency of nocturnal voiding significantly increased with severity of decreased libido. Conclusion: Current cigarette smoking, frequent nocturnal voiding, and a low SHIM score were the independent risk factors for a severely low libido.K Shigehara, Y Kato, M Iijima, et al. Risk Factors Affecting Decreased Libido Among Middle-Aged to Elderly Men; Nocturnal Voiding is an Independent Risk Factor of Decreased Libido. Sex Med 2021;9:100426.

Purpose: Prostate-specific antigen (PSA) is a useful prostate cancer (PC) biomarker, but some cases reported that PSA does not correlate with the Gleason score. Serum chemokine (CC motif) ligand 2 (CCL2) has been reported to be a potential complementary PSA biomarker, but it remains unclear whether it can be applied to non-metastatic castration-sensitive prostate cancer (nmCSPC) or each section of the stages. Serum CCL2′s usefulness was investigated as a prognostic nmCSPC biomarker in this study. Methods: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital from 2007 to 2013. A total of 230 patients with nmCSPC were included in this study of the 255 patients with histologically diagnosed prostate cancer. The serum CCL2 efficacy as a prognostic nmCSPC biomarker was investigated retrospectively. Results: An independent significant predictor of worse OS was CCL2 ≥ 280 pg/dL and CRP ≥ 0.5 mg/dL in multivariate analysis. Gleason score ≥ 8 and CCL2 ≥ 280 pg/dL were independent significant predictors of CRPC-free survival (CFS) worsening in multivariate analysis. Serum CCL2 was a predictive biomarker for OS and CFS in nmCSPC. Furthermore, CCL2 ≥ 280 pg/mL patients had significantly worse visceral metastasis-free survival than those with CCL2 < 280 pg/mL. Conclusion: This study is the first to demonstrate serum CCL2 utility as a biomarker to predict OS and CFS in nmCSPC.

Abstract This open‐label, phase I dose‐finding study evaluated the gonadotropin‐releasing hormone antagonist, TAK‐385, in Japanese patients with nonmetastatic prostate cancer. In a two‐part design, patients received daily oral TAK‐385 at doses of 320 (loading, day 1)/80 (maintenance, day 2 and thereafter), 320/120, 320/160, or 360/120 mg for 28 days in a dose‐escalation phase (part A, n = 13), and at 320/80 or 320/120 mg for up to 96 weeks in a randomized expansion phase (part B, n = 30). Primary endpoint in both parts was safety, including dose‐limiting toxicity in part A. Secondary endpoints included pharmacokinetics, pharmacodynamics, and prostate‐specific antigen concentration. Ten (77%) patients in part A and all patients in part B experienced an adverse event; hot flush (part A, n = 4; part B, n = 15), viral upper respiratory tract infection (part A, n = 1; part B, n = 10), and diarrhea (part B, n = 8) were most frequent. No dose‐limiting toxicities were observed (part A). In 12 evaluable patients (part A), TAK‐385 was rapidly absorbed after a single loading dose; on day 28 (maintenance dose), median steady‐state Tmax was ~1‐2 hours and mean t1/2z was 67‐79 hours. All doses rapidly reduced testosterone concentrations to castration levels within 1 week. Durable reductions in prostate‐specific antigen of >90% from baseline were observed through 96 weeks. TAK‐385 appeared tolerable and resulted in sustained reductions in testosterone to castration levels at all doses. The lowest loading/maintenance dose required for a clinical effect was 320/80 mg. ClinicalTrials.gov: NCT02141659.

Objective: To examine the association between human papillomavirus (HPV) infection and penile cancer among Japanese patients. Methods: Thirty-four patients with penile cancer were enrolled in this study. DNA was extracted from paraffin-embedded tumor tissue samples, and HPV-DNA tests and genotyping were performed. For all of the samples, in situ hybridization (ISH) was performed to locate HPV-DNA in tumor tissue. Furthermore, expression levels of p16-INK4a, mini-chromosome maintenance protein 7 (mcm-7), HPV-L1, and Ki-67 were analyzed using immunohistochemical methods. Results: HPV and high-risk (HR)-HPV were detected in 14 (41.1%; 95% confidence interval (CI) 24.6–57.7%) and 12 (35.2%; 95% CI 19.2–51.4%) cases, respectively. HPV16 was the most frequently detected HPV type. Among the HR-HPV-positive cases, a punctate HR-HPV-DNA signal pattern was detected by ISH in tumor cell nuclei. P16-INK4a was expressed in 66.7% (95% CI 42.8–90.1%) of HR-HPV-positive cases and was significantly more frequent and stronger in HR-HPV-positive cases than in HPV-negative cases. There was no significant difference in the occurrence or distribution of mcm-7 or Ki-67 expression between HPV-positive and HPV-negative cases. HPV-L1 expression was not observed in any of the cases examined. Conclusions: HPV infection may have had an etiological role in 41% of the examined cases of penile cancer in Japan. Keywords: Penile cancer, Human papillomavirus, p16-INK4a, Mini-chromosome maintenance protein 7, Ki-67

Abstract Introduction The incidence of prostate cancer in Japan continues to increase, necessitating the continued development of effective therapies and strategies. Recent advances in treatments have improved the prognosis of metastatic disease and highlighted the importance of treating bone metastases to reduce the incidence of skeletal complications and improve patients’ quality of life. With the increasing number of treatment options that have become available, including bone-targeted therapy with the alpha emitter radium-223 dichloride (Ra-223), Japanese clinicians are faced with making difficult decisions on the choice of optimal treatment strategy. In such situations, guidance based on expert opinions can be beneficial. Methods A panel meeting of 27 Japanese experts in the management of prostate cancer was held to share opinions and to establish consensus recommendations on key clinical questions. Panelists were asked to vote on more than 40 questions pertinent to prostate cancer, and the answers helped guide a comprehensive discussion. Results The panel reached a consensus on key topics related to the optimal treatment strategy for Ra-223 therapy, namely, that patients with symptomatic, metastatic castration-resistant prostate cancer (CRPC) would benefit most from the use of this agent and that this treatment therapy should be provided before chemotherapy. Other topics that achieved consensus included: monitoring for osteoporosis and providing treatment if necessary during androgen deprivation therapy; performing magnetic resonance imaging in the presence of discrepancies in bone scintigram and computed tomography scans; monitoring alkaline phosphatase during CRPC treatment; using osteoclast-targeting in patients with CRPC with bone metastases; and using osteoclast-targeted agents combined with Ra-223. Conclusion These consensus recommendations and the updated information which became available subsequent to the panel meeting included here provide useful information for clinicians to aid in designing optimal treatment strategies for their patients. Funding Bayer Yakuhin Ltd.

In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients’ prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo. The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases – two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.

We examined if the distribution of impaired or normal spermatogenesis differs along the length of seminiferous tubules in disorders of spermatogenesis. For this purpose, three-dimensional (3D) reconstruction of seminiferous tubules was performed in mice with experimental spermatogenesis disorder induced by intraperitoneal injection of busulfan, and the areas of impaired and normal spermatogenesis were analyzed microscopically. The volume of the testis and length of seminiferous tubules decreased, and the proportion of tubule areas with impaired spermatogenesis increased depending on the dose of busulfan. With the highest dose of busulfan, although the proportion of impaired spermatogenesis was similar among individual seminiferous tubules, it was slightly but significantly higher in shorter tubules and in tubule areas near branching points. The tubule areas with impaired and normal spermatogenesis consisted of many segments of varying lengths. With increasing doses of busulfan, the markedly impaired segments increased in length without changing in number, whereas normal segments, although reduced in number and length, remained even with the highest dose of busulfan. Individual remaining normal segments consisted of several different stages, among which stage I and XII were found at higher frequencies, and stage VI at a lower frequency than expected in normal seminiferous tubules. We also examined if the distribution of impaired or normal spermatogenesis differs among different 3D positions in the testis without considering the course of seminiferous tubules. Although the proportions of impaired spermatogenesis with the minimum dose of busulfan and normal spermatogenesis with the highest dose of busulfan greatly varied by location within a single testis, there were no 3D positions with these specific proportions common to different testes, suggesting that the factors influencing the severity of busulfan-induced spermatogenesis disorder are not fixed in location among individual mice.

A 33-year-old female presented to us with a left adrenal cystic tumor with a maximum diameter of 70 mm. Because malignant tumor and pheochromocytoma could not be excluded, she underwent left laparoscopic transperitoneal adrenalectomy. The cystic tumor was stored to an endoscopically inactive treatment device and was subsequently punctured within the device; thus, tumor removal could be performed with minimum incision. Pathological findings showed highly suggestive of a cystic lymphangioma. The punctate was found to have an extremely high catecholamine titer. To avoid unnecessarily exposing the tumor contents, the treatment approach described in this report is reasonable and worth reporting.

A 79-year-old man visited our hospital with a chief complaint of erythema around the urethral orifice of the glans, and a diagnosis of penile Bowen’s disease was made by penile skin biopsy. Initially, local tumor resection with skin grafting from the femoral skin was performed. However, histopathological examination revealed a positive urethral margin of tumor. Since the degree of urethral lesion of penile Bowen’s disease was unclear, the patient received glansectomy. Histopathological examination revealed a tumor lesion in the distal urethra, 7 mm from the external urethral orifice, and confirmed the complete resection of urethral Bowen’s disease. The patient recovered well, with no definite recurrence of Bowen’s disease up to 13 months after partial penectomy. Human papillomavirus 16 DNA was detected in the paraffin-embedded tumor sample, and in situ hybridization confirmed human papillomavirus 16 DNA locations in the tumor tissue. Immunohistochemistry revealed that p16-INK4a was widely expressed in the tumor tissue.

Abstract Background We evaluated the effect of transvaginal mesh (TVM) surgery for voiding function and continence using noninvasive examination and questionnaire. The present study aimed to ascertain which categories of patients need concomitant mid-urethral sling (MUS) after TVM surgery. Methods We included women who underwent TVM procedure between November 2009 and October 2013. Data from noninstrumented uroflowmetry and questionnaires about urinary symptoms were analyzed. Results The present study investigated the cases of 961 women who underwent TVM surgery. The persistence of stress urinary incontinence (SUI) was 57.6%. Almost all the parameters measured using uroflowmetry and questionnaires significantly improved in all types of urinary incontinence 12 months after surgery. A history of hysterectomy, preoperative high flow (corrected maximum flow rate > 1.5), and preoperative urge urinary incontinence were independent risk factors for the persistence of SUI. Conclusions TVM for pelvic organ prolapse improved subjective and objective voiding function. Mixed urinary incontinence (MUI) patients with high urinary flow may be suitable for concomitant MUS with TVM because of the high level of SUI persistence.

Background: This prospective observational study elucidated the usefulness of hormonal therapy for localized prostate cancer. Background factors and the health-related quality of life in patients who initially underwent radical prostatectomy (RP) or primary androgen deprivation therapy (PADT) for localized prostate cancer are summarized. Materials and methods: Patients aged 67–76 years with clinical stage T1c or T2 localized prostate cancer treated with PADT or RP, a prostate-specific antigen concentration of

Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.

Chemokines are a small family of cytokines that were first discovered as chemotactic factors in leukocytes during inflammation, and reports on the relationship between chemokines and cancer progression have recently been increasing. The CCL2-CCR2 axis is one of the major chemokine signaling pathways, and has various functions in tumor progression, such as increasing tumor cell proliferation and invasiveness, and creating a tumor microenvironment through increased angiogenesis and recruitment of immunosuppressive cells. This review discusses the roles of the CCL2-CCR2 axis and the tumor microenvironment in cancer progression and their future roles in cancer therapy.

Abstract Background Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. Methods/design The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. Discussion Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. Trial registration University hospital Medical Information Network (UMIN) Center identifier UMIN000015529 . Registrated 11/1/2014.

Nocturia causes lack of sleep and excessive daytime somnolence, reducing overall well-being, vitality, productivity, and mental health. Nocturia is significantly associated with testosterone deficiency, lower urinary tract symptoms (LUTS), and sleep disorders. The development of LUTS is commonly associated with testosterone deficiency in elderly men, and recent studies have suggested that testosterone has an ameliorative effect on nocturia. In hypogonadal men with nocturia, a negative feedback cycle can arise, in which testosterone deficiency leads to the development of nocturia, and nocturia contributes to the decline in testosterone levels. Therefore, patients with nocturia should receive appropriate treatment in order to improve their quality of life. Nocturia is generally treated by restricting nighttime water intake, as well as by the administration of medications, such as alpha-1 blockers, anticholinergic drugs, and desmopressin. Testosterone replacement therapy (TRT) is used worldwide as a treatment for many hypogonadal conditions. TRT represents an alternative treatment option for nocturia in hypogonadal men. However, limited information is currently available regarding the effects of TRT on nocturia in hypogonadal men, and further studies are required to reach more definitive conclusions.

Abstract Background The chemoresistance of prostate cancer (PCa) is invariably associated with the aggressiveness and metastasis of this disease. New emerging evidence indicates that the epithelial-to-mesenchymal transition (EMT) may play pivotal roles in the development of chemoresistance and metastasis. As a hallmark of EMT, E-cadherin is suggested to be a key marker in the development of chemoresistance. However, the molecular mechanisms underlying PCa chemoresistance remain unclear. The current study aimed to explore the association between EMT and chemoresistance in PCa as well as whether changing the expression of E-cadherin would affect PCa chemoresistance. Methods Parental PC3 and DU145 cells and their chemoresistant PC3-TxR and DU145-TxR cells were analyzed. PC3-TxR and DU145-TxR cells were transfected with E-cadherin-expressing lentivirus to overexpress E-cadherin; PC3 and DU145 cells were transfected with small interfering RNA to silence E-cadherin. Changes of EMT phenotype-related markers and signaling pathways were assessed by Western blotting and quantitative real-time polymerase chain reaction. Tumor cell migration, invasion, and colony formation were then evaluated by wound healing, transwell, and colony formation assays, respectively. The drug sensitivity was evaluated using MTS assay. Results Chemoresistant PC3-TxR and DU145-TxR cells exhibited an invasive and metastatic phenotype that associated with EMT, including the down-regulation of E-cadherin and up-regulation of Vimentin, Snail, and N-cadherin, comparing with that of parental PC3 and DU145 cells. When E-cadherin was overexpressed in PC3-TxR and DU145-TxR cells, the expression of Vimentin and Claudin-1 was down-regulated, and tumor cell migration and invasion were inhibited. In particular, the sensitivity to paclitaxel was reactivated in E-cadherin-overexpressing PC3-TxR and DU145-TxR cells. When E-cadherin expression was silenced in parental PC3 and DU145 cells, the expression of Vimentin and Snail was up-regulated, and, particularly, the sensitivity to paclitaxel was decreased. Interestingly, Notch-1 expression was up-regulated in PC3-TxR and DU145-TxR cells, whereas the E-cadherin expression was down-regulated in these cells comparing with their parental cells. The use of γ-secretase inhibitor, a Notch signaling pathway inhibitor, significantly increased the sensitivity of chemoresistant cells to paclitaxel. Conclusion The down-regulation of E-cadherin enhances PCa chemoresistance via Notch signaling, and inhibiting the Notch signaling pathway may reverse PCa chemoresistance.

Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer (CRPC) has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen (PSA). However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.

α-Trifluoromethyl chalcones were prepared and evaluated for their antiproliferative activities against androgen-independent prostate cancer cell lines as well as five additional types of human tumor cell lines. The most potent chalcone 5 showed superior antitumor activity in vivo with both oral and intraperitoneal administration at 3 mg/kg. Cell-based mechanism of action studies demonstrated that 5 induced cell accumulation at sub-G1 and G2/M phases without interfering with microtubule polymerization. Furthermore, several cancer cell growth-related proteins were identified by using chalcone 5 as a bait for the affinity purification of binding proteins.

Recent advances in prostate cancer (PC) research unveiled real androgen receptor (AR) functions in castration-resistant PC (CRPC). Moreover, AR still accelerates PC cell proliferation via the activation of several mechanisms (e.g., mutation, variants, and amplifications in CRPC). New-generation AR signaling-targeted agents, inhibiting extremely the activity of AR, were developed based on these incontrovertible mechanisms of AR-induced CRPC progression. However, long-term administration of AR signaling-targeted agents subsequently induces the major problem that AR (complete)-independent CRPC cells present neither AR nor prostate-specific antigen, including neuroendocrine differentiation as a subtype of AR-independent CRPC. Moreover, there are few treatments effective for AR-independent CRPC with solid evidence. This study focuses on the transformation mechanisms of AR-independent from AR-dependent CRPC cells and potential treatment strategy for AR-independent CRPC and discusses them based on a review of basic and clinical literature.