Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/iju5.70079

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Introduction Currently, androgen deprivation therapy (ADT) plays a key role in treating advanced prostate cancer, particularly in elderly patients. With the advent of gonadotropin-releasing hormone (GnRH) medications, ADT has shifted from surgical to medical castration. While GnRH agonists and antagonists remain mainstream treatments for prostate cancer, there has been no research comparing the burden each drug places on patients. Methods A study conducted at Yokohama City University Medical Center analyzed 851 hormonal injections administered between August 2018 and February 2019. The study evaluated the time from prescription to completion of injection, as well as the perceived physical and mental burden on patients. Results showed that injections of degarelix took significantly longer time to injection than other treatments. Leuprorelin 22.5 mg most effectively reduced outpatients' hospital visits, primarily due to its six-month dosing interval and convenient kit formulation. Degarelix required a longer process, including drug dilution and cooling of the injection site to prevent potential skin reactions, contributing to its extended administration time. Results In terms of patient burden, leuprorelin 22.5 mg was associated with the least discomfort, showing minimal difference from the oral formulation. One limitation of this study is that the method of leuprorelin administration in Japan (subcutaneous injection) differs from that in other countries (intramuscular injection). Conclusion In summary, the six-month leuprorelin 22.5 mg regimen reduces hospital time. Patient burden was also considered a factor in the selection of GnRH preparations.

DOI： 10.7759/cureus.84881

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Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Introduction: Immune checkpoint inhibitors are the mainstay of treatment for unresectable or metastatic renal cell carcinoma (RCC). However, they can cause immune-related adverse events (irAEs), and the management of these irAEs is critical. The combination of myasthenia gravis, myositis, and myocarditis, which are irAEs, is rare, and it has not been reported to occur with avelumab. This report aimed to present a rare case of RCC metastasis that developed irAEs during avelumab and axitinib combination therapy. Case Presentation: A 76-year-old woman who underwent radical nephrectomy for clear cell RCC (pT1bN0M0 Grade 3 INFb) at the age of 67 years presented to our hospital after her family doctor noted a pancreatic tumor. She was diagnosed with pancreatic metastasis of RCC based on histopathological examination, and avelumab and axitinib combination therapy was initiated. She developed irAEs, including myasthenia gravis, myositis, and myocarditis, which were treated with steroid pulse therapy. The patient recovered after treatment and was discharged without sequelae. Conclusion: Myasthenia gravis, myositis, and myocarditis can occur during avelumab and axitinib combination therapy for RCC. Prompt diagnosis, treatment, and collaboration with other departments are extremely important for managing irAEs.

DOI： 10.1159/000545733

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OBJECTIVES: This retrospective study aimed to compare the surgical outcomes of holmium laser enucleation of the prostate (HoLEP) and transurethral vaporization techniques between the elderly and nonelderly patients with benign prostatic enlargement (BPE). METHODS: We retrospectively analyzed clinical data from two regional centers that used HoLEP and transurethral vaporization techniques for BPE treatment. The study population consisted of male patients with lower urinary tract symptoms, divided into elderly and nonelderly groups. RESULTS: Total 477 of 872 patients remained in the study, of which 198 were classified as elderly (age ≥ 75 years) and 279 as non-elderly (age < 75 years). The postoperative decrease in IPSS was significantly lower in the elderly group, and advanced age was associated with less IPSS decline only after vaporization (p = 0.003) but not after HoLEP. In both surgeries, the duration of postoperative catheterization was significantly longer in the elderly group than in the non-elderly group, and hemoglobin drop at 1 day postoperatively showed no age-related difference. The most common complication after HoLEP was intermittent incontinence, which was more frequent in the elderly group (15.0%) than in the non-elderly group (6.2%, p = 0.038). Regardless of age, the overall rate of need for medication at 6 months postoperatively was significantly higher after HoLEP (32/190, 16.8%) than after transurethral vaporization (30/287, 10.5%) (p = 0.042). The need for medication was higher in the elderly for both HoLEP and vaporization than in the non-elderly group with a specific cutoff of age. CONCLUSIONS: Elderly patients with BPE had relatively worse surgical outcomes, including a higher need for postoperative medications and prolonged catheterization. HoLEP demonstrated a reduction in IPSS regardless of age, and transurethral vaporization did not, although it was associated with a higher rate of intermittent incontinence.

DOI： 10.1111/luts.70010

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1159/000548719

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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INTRODUCTION: 45,X/46,XY mosaicism is a rare anomaly in sexual differentiation, presenting with diverse phenotypes and often leading to infertility due to abnormal gonadal development. AIMS: This report aims to present a case study of a 45,X/46,XY mosaic male patient with an ejaculatory disorder attributed to seminal vesicle dysplasia. METHODS: In this case study, diagnostic procedures encompassed blood tests, semen analysis, chromosomal examination, and imaging studies to assess gonadal morphology. Treatment strategies included attempted varicocelectomy, pharmacological intervention with amoxapine, and surgical testicular sperm extraction. Additionally, the patient underwent assisted reproductive techniques, specifically intracytoplasmic sperm injection (ICSI), to facilitate pregnancy for his wife. RESULTS: A 32-year-old man could not ejaculate, with post-orgasmic urinalysis revealing minimal sperm presence. Chromosomal analysis confirmed 45,X/46,XY mosaicism. Despite undergoing microsurgical varicocelectomy for clinical varicocele and receiving tricyclic antidepressants, no improvement in semen volume occurred. Imaging studies indicated ejaculatory disorder due to prostate and seminal vesicle aplasia. Consequently, surgical retrieval of testicular sperm was performed, leading to successful pregnancy via ICSI for his wife. CONCLUSION: Our approach has effectively addressed ejaculatory disorder in 45,X/46,XY mosaic men, resulting in successful pregnancy.

DOI： 10.1093/sexmed/qfae066

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A regulatory mechanism for SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule, is incompletely understood. Here, we report an important regulation of SLC family transporter by SETD2, a chromatin remodeling gene whose alterations have been found in a subset of kidney cancers. Kidney-specific inactivation of Setd2 resulted in hypovolemia with excessive urine excretion in mouse and interestingly, RNA-sequencing analysis of Setd2-deficient murine kidney exhibited decreased expressions of SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule. Importantly, inactivation of Setd2 in murine kidney displayed attenuated dapagliflozin-induced diuresis and glucose excretion, further supporting that SETD2 might regulate SLCfamily transporter-mediated sodium and glucose reabsorptions in renal tubule. These data uncover an important regulation of SLC family transporter by SETD2, which may illuminate a crosstalk between metabolism and epigenome in renal tubule.

DOI： 10.1016/j.bbrc.2024.150730

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Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

DOI： 10.21037/tau-24-21

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INTRODUCTION: In the United States, a total of 268,490 men were found to have prostate cancer in 2022, thus making it the most common cancer in men, accounting for 27% of all cancers in the male population. Among all cancers in men, it was the fifth leading cause of death, with 34,500 deaths and a mortality rate of 11%. In 2019, the total number of cases was 94,748, making it the leading cancer in males, accounting for 11% of all male cancers. In terms of mortality, it ranked seventh, with 13,217 deaths and a mortality rate of 1.6%. However, new treatment options for metastatic castration-sensitive prostate cancer (mCSPC) have emerged. Docetaxel has been shown to be effective for both mCSPC and castration-resistant prostate cancer (CRPC). Upfront docetaxel has not been approved in Japan, nor has it been validated in large-scale studies. Furthermore, several agents can be used after docetaxel treatment, but it is unclear which is the most effective. We used a large Japanese health insurance database to determine which agent would be the most effective as a next-line therapy in patients who had received docetaxel. MATERIALS AND METHODS: We used data from medical institutions using the Diagnosis Procedure Combination (DPC), which provides a comprehensive evaluation of medical classifications. The Medical Data Vision database covers approximately 23% of DPC hospitals in Japan. This study analyzed 2938 patients with mCSPC who received docetaxel, followed by CRPC, between April 2008 and December 2021. The study focused on three agents: enzalutamide, abiraterone acetate, and cabazitaxel. Other agents were excluded due to the small number of patients. The following data were analyzed: age, date of CRPC diagnosis, presence of bone metastasis, drug type, and prognosis. RESULTS: This study included 1997 patients with CRPC after upfront docetaxel therapy for mCSPC (enzalutamide [ENZ] group, n = 998; abiraterone acetate [ABI] group, n = 617; and cabazitaxel [CBZ] group, n = 382). The overall survival (OS) time from drug initiation was 456 days in the enzalutamide group, which was significantly longer than that in the cabazitaxel group (p = 0.017, HR 0.94) (ENZ: ABI p = 0.54, HR 0.94; ABI: CBZ p = 0.14, HR 0.75). OS was also compared for the third-line drug in the group that received enzalutamide as the second-line drug, the group that used abiraterone acetate as the third-line drug (ENZ-ABI group), and the group that used abiraterone acetate as the second-line drug. OS from the start of the third-line drug was compared between the ENZ-ABI group and the ABI-ENZ group, which received enzalutamide as the third-line drug, but showed no significant difference (269 vs. 281 days, p = 0.85; HR 1.03). CONCLUSION: ENZ was shown to prolong OS relative to cabazitaxel after the cessation of docetaxel. ENZ was associated with a longer duration of drug use than ABI and CBZ.

DOI： 10.3390/diseases12070162

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OBJECTIVES: This study investigated the effects of prostate surgery on storage symptoms in male patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE). This study aimed to identify patient characteristics associated with improved, unchanged, and deteriorated post-surgical storage symptoms and to identify the risk factors for non-improvement or deterioration. METHODS: A retrospective analysis of 586 prostate surgeries performed between 2016 and 2022 at Yokosuka Kyosai Hospital was conducted on patients with LUTS and at least one storage symptom preoperatively. Patients with active urinary tract infection, prostate/bladder cancer, urethral strictures, or dementia were excluded. The study enrolled 230 patients and assessed storage symptoms using the International Prostate Symptom Score (IPSS). RESULTS: Overall, storage symptoms improved, remained unchanged, and deteriorated in 87.0%, 5.7%, and 7.4% of patients, respectively. The patients in the deteriorated group were significantly older, whereas those in the no-change group had smaller prostate volumes. Patient-reported outcome scores (IPSS, IPSS-QoL, and BII) were significantly higher in the improved group. The predictors of non-improvement included low IPSS storage score, cardiovascular disease, and diabetes mellitus. Predictors of deterioration included advanced age and low IPSS storage score. CONCLUSIONS: Patients with severe LUTS showed greater postoperative improvement in storage symptoms. A low IPSS storage score predicted non-improvement and deterioration. Advanced age, low IPSS storage score, and a history of cardiovascular disease and diabetes mellitus were identified as key predictors. Awareness of these factors may guide preoperative counseling and improve decision-making in prostate surgery, ensuring more personalized and effective treatment strategies.

DOI： 10.1111/luts.12512

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Objective: Complete endophytic renal tumors (CERTs) are the most challenging for robot-assisted partial nephrectomy (RAPN). This study aimed to determine the impact of CERT on outcomes of RAPN. Methods: All RAPN cases for localized renal tumor undertaken at Yokohama City University Hospital between 2016 and 2023 were enrolled. Tumor characteristics and surgical, functional, and oncologic outcomes of RAPN were compared between CERT and non-CERT groups. Results: Consecutive 666 patients were enrolled, and 76 (11.4%) were identified as CERT (3 points of "E" score). CERT showed smaller tumor diameters (p < 0.001), more predominant hilar tumor (p = 0.029), higher "N" scores (p < 0.001) and "L" scores (p = 0.006) than non-CERT. The CERT group showed longer warm ischemia times (p < 0.001), more frequent positive surgical margins (p = 0.028), and relatively lower trifecta achievement rates (p = 0.101) than the non-CERT group. In multivariable analysis, the CERT was an independent predictor for trifecta achievement but not for pentafecta achievement. Conclusions: CERT was associated with longer warm ischemia time, positive surgical margin, and lower trifecta achievement, but not with surgical complication and pentafecta achievement in RAPN. This study suggested that CERT had limited influence on long-term renal functional preservation; however, it had strong impacts on short-term surgical outcome.

DOI： 10.1089/end.2023.0608

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The influence of chronic kidney disease stage on robot-assisted partial nephrectomy outcomes remains underexplored. This study aimed to assess the impact of chronic kidney disease stage on functional and surgical outcomes of robot-assisted partial nephrectomy and identify preoperative predictors of significant postoperative 1-year renal-function loss (RFL). Clinical data of 408 patients who underwent robot-assisted partial nephrectomy at Yokohama City University Hospital between 2016 and 2023 were retrospectively reviewed. The da Vinci Surgical System was applied in all patients, and outcomes assessed included surgical parameters, postoperative estimated glomerular filtration rate, trifecta and pentafecta achievements, and complications. Significant RFL was defined as estimated glomerular filtration rate reduction ≥ 25% from baseline. Higher chronic kidney disease stages correlated with older age, hypertension, diabetes, and solitary kidneys. Postoperative estimated glomerular filtration rate decline was most pronounced in patients with chronic kidney disease stages 4-5. Although the chronic kidney disease stage did not significantly affect most surgical parameters, pentafecta achievement was higher in patients with chronic kidney disease stage 3 than in those with stages 4-5. Two patients required hemodialysis after robot-assisted partial nephrectomy. Multivariable logistic regression analysis showed that preoperative hemoglobin level and maximum tumor diameter were significant predictive factors for significant RFL. In conclusion, preoperative CKD stage did not influence on surgical outcome except for pentafecta achievement. RAPN may be feasible for patients with CKD stages 4-5 because of no rapid progression to hemodialysis induction and no procedure-related mortality. Preoperative hemoglobin levels and tumor diameter emerged as predictors of significant RFL.

DOI： 10.1007/s11701-024-01873-2

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OBJECTIVE: In December 2021, enfortumab vedotin (EV), an antibody-drug conjugate directed against nectin-4, was approved in Japan as a new treatment after platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. This study evaluated, using real-world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). MATERIALS AND METHODS: Fifty-five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non-EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. RESULTS: The median (range) follow-up period after pembrolizumab discontinuation was 6.3 (0.7-31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non-EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non-EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non-EV group; hazard ratio 0.26; 95% confidence interval 0.16-0.41; p < 0.001) was an independent prognostic factor for OS. CONCLUSION: EV prolonged OS in mUC following pembrolizumab therapy in real-world data.

DOI： 10.1111/iju.15437

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Urological Association  

DOI： 10.5980/jpnjurol.115.33

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BACKGROUND/AIM: When hormone therapy (HT) is combined with radiotherapy, understanding the recovery of testosterone levels after the end of HT becomes crucial for considering subsequent therapy. The aim of this study was to determine the factors influencing the time to recovery of testosterone levels after discontinuation of HT and the likelihood of recovery. PATIENTS AND METHODS: The study included a total of 108 patients with prostate cancer who were treated with GnRH agonist in combination with radiotherapy and followed up for at least 12 months after discontinuation of the GnRH agonist. The presence of recovery of testosterone levels and the time to recovery were investigated. Univariate and multivariate analyses were performed on several factors contributing to testosterone recovery, including age at initiation of HT, and the duration of HT. RESULTS: Testosterone levels recovered in 61 cases (56.5%). The median time to recovery was 14.8 months. There was a significant difference in the recovery of testosterone levels between patients aged ≥71 years and those aged <71 years at the start of HT (p=0.002), and between those who had been on HT for ≥34 months and those for <34 months (p=0.031). In both univariate and multivariate analyses, age at initiation of HT and duration of HT contributed to the recovery of testosterone levels. CONCLUSION: The rate of recovery of testosterone levels after long-term (median 34.3 months) HT was lower in patients who were older than 71 years at the start of HT.

DOI： 10.21873/invivo.13666

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BACKGROUND: Late-onset hypogonadism (LOH) is a condition caused by the decline of testosterone levels with aging and is associated with various symptoms, including lower urinary tract symptoms (LUTSs). Although some reports have shown that testosterone replacement treatment for LOH improves LUTSs, no large study has revealed a correlation between LUTSs and LOH. This study investigated the correlation between the severity of LOH and LUTSs in Japanese males >40 years of age using a web-based questionnaire with the Aging Males' Symptoms (AMS) scale. METHODS: We asked 2000 Japanese males to answer both the AMS and IPSS/QOL questionnaires using a web-based survey. Among these 2000 individuals, 500 individuals were assigned to each age group. RESULTS: The IPSS total score was positively correlated with the severity of AMS (shown as median [mean ± SD]): no/little group, 2 (3.67 ± 5.36); mild group, 6 (7.98 ± 6.91); moderate group, 11 (12.49 ± 8.63); and severe group, 16 (14.83 ± 9.24) (p < 0.0001). CONCLUSIONS: Individuals with higher AMS values, representing cases with severe LOH symptoms, had a higher risk of experiencing nocturia and LUTSs than those with lower AMS values.

DOI： 10.3390/jcm12247528

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Language：English   Publisher：(一社)日本癌学会  

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OBJECTIVE: To investigate the trial of spontaneous urination without catheter (TWOC) outcomes for men with acute urinary retention, determine successful TWOC predictors, and evaluate the impact of add-on medication therapy on TWOC. METHODS: This retrospective study included men with acute urinary retention and post-void residual (PVR) >250 mL who underwent TWOC between July 2009 and July 2019. Patients were divided into a medicated group who received alpha1 blocker on urinary retention diagnosis and a naïve group who did not. The trial was defined as unsuccessful if the PVR was >150 mL or if the patient experienced difficulty emptying their bladder with abdominal discomfort or pain, and a transurethral catheter was reinserted. RESULTS: Among 576 men with urinary retention, 269 (46.7%) constituted the medicated group and 307 (53.3%) the naïve. The naïve group comprised more elderly patients (P = 0.010) with higher Eastern Cooperative Oncology Group performance status (PS) (P = 0.001) and smaller prostate volume (P = 0.028) than the other. In the medicated group, 153 men received additional oral medication before TWOC to increase the success rate. There were significant age differences (P = 0.041) in the medicated group and significant median PS differences (P = 0.010) in the naïve group between the successful and unsuccessful outcomes of TWOC. The multivariate logistic regression model demonstrated that age <80 years in medicated patients (P = 0.042, odds ratio [OR] 1.701) and PS <2 in naïve patients (P = 0.001, OR 2.710) were significant independent predictors of successful TWOC outcomes. CONCLUSIONS: This is the first study classifying patients with urinary retention according to medication status. Both medicated and naïve groups had different patient backgrounds and TWOC outcome predictors, suggesting a discrepant etiology behind urinary retention. Hence, acute urinary retention management in men should vary based on medication status for male lower urinary tract symptoms when urinary retention is diagnosed.

DOI： 10.1111/luts.12492

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BACKGROUND: Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who have previously received platinum-based chemotherapy and an immune-checkpoint inhibitor. The EV-301 phase III trial demonstrated significantly improved overall survival and response rates compared to standard chemotherapy. However, more data, especially from larger real-world studies, are needed to further assess its effectiveness in Japanese patients. METHODS: A total of 6007 urothelial cancer patients inducted with pembrolizumab as a second-line treatment were analyzed. Among them, 563 patients received enfortumab vedotin after pembrolizumab, while 443 patients received docetaxel or paclitaxel after pembrolizumab, and all were included in the study for efficacy as a life prolonging agent. RESULTS: The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). In multivariate analysis, enfortumab vedotin induction was the independent risk factor for overall survival (p = 0.013, HR: 0.70). There were no significant differences in cancer-specific survival. CONCLUSIONS: Enfortumab vedotin prolonged the overall survival for Japanese advanced or metastatic urothelial carcinoma patients compared to paclitaxel or docetaxel after pembrolizumab treatment.

DOI： 10.3390/cancers15174227

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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OBJECTIVES: Depression might worsen lower urinary tract symptoms (LUTS), but the correlation is still disputed. This study examined the influence of depression on LUTS in Japanese women. METHODS: This study used a web-based questionnaire to evaluate the mental status of depression and LUTS. The mental status of depression was evaluated using the Quick Inventory of Depressive Symptomatology-Japanese version (QIDS-J), and LUTS was assessed based on the Overactive Bladder Symptom Score (OABSS) and responses to the International Consultation on Incontinence Questionnaire-Short Form. RESULTS: A total of 4151 of 5400 (76.9%) women responded to the questionnaire. The mean age was 48.3 ± 13.8 years. The OABSS gradually increased with the QIDS-J score. The incidence of overactive bladder (OAB) and urgency urinary incontinence (UUI) also increased along with the QIDS-J score. In the younger age group (20-39 years old), the risks of OAB and UUI were higher than in the elderly group (7.42 for OAB and 7.44 for UUI). CONCLUSIONS: This study revealed that worsening of LUTS was correlated with depression.

DOI： 10.1111/luts.12478

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

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BACKGROUND: Despite the widespread availability of medication choices for metastatic castration-resistant prostate cancer (mCRPC), biomarkers to predict the efficacy of each mCRPC treatment have not yet been established. This study developed a prognostic nomogram and a calculator to predict the prognosis of patients with mCRPC who received abiraterone acetate (ABI) and/or enzalutamide (ENZ). METHODS: In total, 568 patients with mCRPC who underwent ABI and/or ENZ between 2012 and 2017 were enrolled. A prognostic nomogram based on the risk factors was developed using the Cox proportional hazards regression model and clinically important factors. The discriminatory ability of the nomogram was assessed according to the concordance index (C-index). A 5-fold cross-validation was repeated 2000 times to estimate the C-index, and the means of the estimated C-index for the training and validation sets were determined. A calculator based on this nomogram was then developed. RESULTS: The median overall survival (OS) was 24.7 months. Multivariate analysis showed that the time to CRPC, pre-chemotherapy, baseline prostate-specific antigen, baseline alkaline phosphatase, and baseline lactate dehydrogenase levels were independent risk factors for OS (hazard ratio [HR]: 0.521, 1.681, 1.439, 1.827, and 12.123, p = 0.001, 0.001,  < 0.001, 0.019, and  < 0.001, respectively). The C-index was 0.72 in the training cohort and 0.71 in the validation cohort. CONCLUSIONS: We developed a nomogram and calculator to predict OS in Japanese patients with mCRPC who received ABI and/or ENZ. Reproducible prognostic prediction calculators for mCRPC will facilitate greater accessibility for clinical use.

DOI： 10.1186/s12885-023-10700-0

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Language：Japanese   Publisher：医学図書出版(株)  

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OBJECTIVE: To investigate the outcome, determine the predictors for the success of, and evaluate the efficacy of pharmacokinetic therapy on trial catheter removal for women with urinary retention. METHODS: Inclusion criteria were female patients with acute urinary retention defined as painful, palpable, or percussive bladder, when the patient is unable to pass any urine, accompanied by postvoid residual (PVR) > 250 ml, and who underwent trial catheter removal between July 2009 and July 2019. Before trial catheter removal, alpha-blockers alone or alpha-blockers and parasympathomimetics (bethanechol or distigmine bromide) were used to facilitate spontaneous voiding in some cases. RESULTS: Fifty-nine of 104 (56.7%) women with urinary retention were catheter-free post trial. There was no significant difference between successful and non-successful trials in average age (p = .392), median ECOG (Eastern Cooperative Oncology Group) performance status (p = .374), diabetes mellitus (p = .842), dementia (p = .801), previous history of cerebrovascular events (p = .592), or intrapelvic surgery (p = .800). Oral medications were administered for 39/59 (66.1%) in the success group and 30/45 (66.7%) patients in the non-success groups (p = .598). Serum albumin (3.2 ± 0.7 g/dl and 2.8 ± 0.8 g/dl, p = .039) and total protein values (6.5 ± 0.8 g/dl and 6.0 ± 1.0 g/dl, p = .038) at diagnosis of urinary retention were higher in the success group than the non-success group, respectively. Multivariate logistic regression found that a serum albumin >3 g/dl was an independent predictor of successful trial catheter removal for women with urinary retention (p = .030, odds ratio [OR] 3.3, 95% confidence interval [CI] of OR 1.1-9.9). Age < 70 years old was a likely predictor of successful trial catheter removal (p = .066, OR 4.8, 95% CI of OR 0.9-25.0). CONCLUSIONS: This is the first retrospective study to investigate the predictive factors for successful trial catheter removal in women with urinary retention. A serum albumin value >3 mg/dl at diagnosis of urinary retention was a significant independent predictor of catheter-free status after trial catheter removal, and age < 70 years-old was a possible contributor. There was no evidence that oral medication contributed to catheter-free status.

DOI： 10.1111/luts.12464

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BACKGROUND: There is no consensus on the role of serum dehydroepiandrosterone (DHEA) concentrations in the detection of prostate cancer. This study examined the effectiveness of serum DHEA in predicting candidate patients for active surveillance (AS) prior to prostate biopsy. METHODS: A systematic prostate needle biopsy was performed in 203 men with serum PSA levels of < 10 ng/mL to detect prostate cancer. Serum DHEA concentrations were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) just before biopsy. Patient's age, serum prostate-specific antigen (PSA) levels, prostate volume, and serum DHEA concentrations were compared with pathological findings in multivariate analyses. RESULTS: The median patient's age, PSA, serum DHEA concentration and prostate volume were 68 years, 5.5 ng/mL, 1654.7 pg/mL, and 31.2 mL, respectively. In a multivariate analysis, low PSA values, high serum DHEA concentrations, and large prostate volume were significant predictors of the patients with benign prostatic hyperplasia (BPH) or prostate cancer with a Gleason score of ≤ 3 + 4 who are candidate for AS. The DHEA cut-off point for predicting BPH or prostate cancer with a Gleason score of ≤ 3 + 4 was 2188 pg/mL, with a sensitivity, specificity, positive predictive value, and negative predictive value of 33.7%, 96.0%, 98.4%, and 16.9%, respectively. CONCLUSION: The study indicated that higher serum DHEA concentrations prior to prostate biopsy might predict the patients with BPH or prostate cancer with a Gleason score ≤ 3 + 4 who are candidate for AS, in men with PSA of < 10 ng/mL.

DOI： 10.1186/s12885-022-10251-w

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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DOI： 10.1111/iju.15047

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：English   Publisher：(一社)日本癌治療学会  

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Introduction: We report a case series of six patients with a chief complaint of infertility who underwent microsurgical varicocelectomy for intratesticular varicocele (ITV) after undergoing orchiopexy for undescended testis in their childhood. Case presentation: The patients' median age was 34 years. The median age at which orchiopexy was performed was 4.5 years. All the cases of ITV were accompanied by extratesticular varicocele (ETV). All the patients underwent a microsurgical subinguinal varicocelectomy. At 3 months after operation, the ITV and ETV had disappeared in all the cases. Sperm density and motility increased in five and four patients, respectively. Conclusion: ITV occurs at a relatively high frequency after orchiopexy for undescended testis. Disorder of the valvular function of the testicular vein in peeling the testicular vessels was thought to be a primary cause and is often found on the left side. Doppler ultrasonography of the testis is considered important for diagnosis.

DOI： 10.1002/iju5.12498

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BACKGROUND: The ALSYMPCA trial revealed radium-223 (Ra-223) to be a life-prolonging agent for bone metastatic castration-resistant prostate cancer (CRPC). However, only 2.8% of enrolled patients in that clinical trial were Asian, and no Japanese patients were enrolled. Several retrospective studies have been published concerning Japanese bone metastatic CRPC patients receiving Ra-223. However, no study has yet reported the correlation between Ra-223 induction and the survival in Japanese bone metastatic CRPC patients. This study investigated the effect of Ra-223 as a life-prolonging agent in a large Japanese healthcare fee database. METHODS: A total of around 410 000 prostate cancer patients were extracted from this database, and 25 934 were diagnosed with CRPC. In these patients, the age, date of the CRPC diagnosis, date of Ra-223 induction, and prognosis were analyzed. RESULTS: A total of 1628 patients received Ra-223, and 6693 patients were diagnosed with bone metastasis CRPC, with the remaining 17 613 patients diagnosed with CRPC without bone metastasis. The patients who completed six courses of Ra-223 showed a significantly more favorable overall and cancer-specific survival than those who received ≤5 courses (p < 0.0001 and p < 0.0001, respectively). For time from CRPC diagnosis date to death, the Ra-223 induction group showed a significantly more favorable prognosis with regard to both the overall and cancer-specific survival than the bone metastatic CRPC patients without Ra-223 (p < 0.0001 and p < 0.0001, respectively). CONCLUSIONS: Bone metastatic CRPC patients who received Ra-223 showed a significantly better prognosis than bone metastatic CPRC patients who did not receive Ra-223.

DOI： 10.1111/iju.15008

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：日本小児泌尿器科学会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.isci.2022.104463

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：医学図書出版(株)  

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DOI： 10.1016/j.ajur.2020.05.006

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Language：Japanese   Publisher：日本小児泌尿器科学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Impact Journals LLC  

DOI： 10.18632/oncotarget.27944

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PURPOSE: We evaluated the predictive factors for completion of all six cycles of radium-223 (Ra-223) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). We also developed a novel prediction model for Ra-223 treatment completion using these predictors. METHODS: We retrospectively reviewed data from 122 patients with mCRPC who were treated with Ra-223. The predictive factors for the completion of six cycles of Ra-223 treatment were evaluated. Statistically significant predictive factors were then used to develop a prediction model for treatment completion. Finally, using this prediction model, we classified the overall survival (OS) of the entire cohort into three groups. RESULTS: We identified three significant variables as the predictive factors for treatment completion: baseline alkaline phosphatase (ALP) level, baseline hemoglobin (Hb) level, and baseline pain. The three groups generated using the prediction model were: group 1 (patients with three predictive factors, i.e., ALP < median, Hb ≥ median, and no pain), group 2 (patients with one to two predictive factors), and group 3 (patients without any predictive factors). The treatment completion rates differed between the three groups significantly. Furthermore, the OS also differed among the groups significantly. CONCLUSION: Our study suggested that the baseline ALP level, baseline Hb level, and baseline pain were the predictive factors of completion of all six cycles of Ra-223 treatment in patients with mCRPC. Our prediction model consisting of these factors could predict not only the completion of Ra-223 treatment, but also the post-treatment survival. This model can thus be useful for selection of patients for Ra-223 treatment.

DOI： 10.1007/s00345-021-03639-z

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(株)癌と化学療法社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00296&link_issn=&doc_id=20210122250009&doc_link_id=%2Fab8gtkrc%2F2021%2F004801%2F010%2F0046-0051%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2021%2F004801%2F010%2F0046-0051%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: To investigate the efficacy and safety of a second-generation bipolar transurethral electro vaporization of the prostate (B-TUVP) with the new oval-shaped electrode for large benign prostatic enlargement (BPE) with prostate volume (PV) ≥100ml. MATERIALS AND METHODS: 100 patients who underwent second-generation B-TUVP with the oval-shaped electrode for male lower urinary tract symptom (LUTS) or urinary retention between July 2018 and July 2020 were enrolled in this study. The patients' characteristics and treatment outcome were retrospectively compared between patients with PV <100ml and ≥100ml. RESULTS: 17/41 (41.5%) cases of PV ≥100ml and 24/59 cases (40.7%) of PV <100ml were catheterised due to urinary retention. The duration of post-operative catheter placement and hospital-stay of PV ≥100ml (3.1±1.3 and 5.6±2.3 days) were not different from PV <100ml (2.7±1.2 and 5.0±2.4 days). In uncatheterised patients (N = 59), post-void residual urine volume (PVR) significantly decreased after surgery in both groups, however, maximum uroflow rate (Qmax) significantly increased after surgery only in PV <100ml but not in PV ≥100ml. Voiding symptoms and patients' QoL derived from International Prostate Symptom Score (IPSS), IPSS-QoL (IPSS Quality of Life Index) and BPH Impact Index (BII) scores, significantly improved after B-TUVP in both groups. Catheter free status after final B-TUVP among patients with preoperative urinary retention was achieved in 18/24 (75.0%) and 14/17 (82.1%) cases in patient with <100ml and ≥100ml, respectively. There was no significant difference in post-operative Hb after B-TUVP, which was 97.0±5.4% of baseline for PV <100ml and 96.9±6.1% for PV ≥100ml and no TUR syndrome was observed. CONCLUSIONS: This is the first study investigating short-term efficacy and safety of second-generation B-TUVP with the oval-shaped electrode on large BPE. B-TUVP appears to be effective and safe for treating moderate-to-severe lower urinary tract symptoms and urinary retention in patients with large BPE.

DOI： 10.1371/journal.pone.0261586

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Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Ureteral stent encrustation is sometimes encountered, especially in cases in which a ureteral stent has been forgotten. An 84-year-old female patient with malignant myeloma underwent metallic ureteral stent insertion to treat malignant ureteral obstruction. At the time of scheduled ureteral stent exchange, the stent was heavily encrusted and could not be removed on either side. We performed endoscopic lithotripsy to remove the encrusted ureteral stents. The bilaterally encrusted metallic ureteral stents were successfully removed using Ho:YAG laser lithotripsy after inserting another ureteral stent placement besides the encrusted metallic ureteral stents.

DOI： 10.1159/000511601

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Research  

DOI： 10.1038/s41598-020-77223-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

DOI： 10.1111/iju.14357

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J06262&link_issn=&doc_id=20201211310014&doc_link_id=%2Fem0sfcrt%2F2020%2F000802%2F014%2F0256-0259%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fem0sfcrt%2F2020%2F000802%2F014%2F0256-0259%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/ccr3.3507

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.3507

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Recent studies have shown that several inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), lymphocyte-to-platelet ratio (LPR), De Retis and prognostic nutritional index (PNI), can function as useful prognostic factors in a number of malignancies. The present study aimed to assess the most reliable inflammatory tumor marker in patients with bladder cancer who have undergone radical cystectomy. A total of 161 cases underwent radical cystectomy between 1994 and 2014 at Yokohama City University Medical Center (Yokohama, Japan). Of these patients, the 107 who had data for the NLR, MLR, LPR, De Retis and PNI were enrolled in the present study. The correlation between recurrence-free survival (RFS) or overall survival (OS) and inflammatory tumor markers were examined. Regarding the RFS, the only noteworthy finding was that a lower PNI was associated with a significantly poorer RFS compared with higher PNI (P=0.028). Regarding the OS, lower LPR and PNI were associated with a significantly poorer OS compared with higher values (P=0.048 and P=0.036, respectively). The present study revealed that a low PNI more accurately predicts a worse RFS and OS compared with other systemic inflammatory risk factors.

DOI： 10.3892/mco.2020.2117

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Background: At present, one out of six couples is infertile, and in 50% of cases, infertility is attributed to male infertility factors. Genetic abnormalities are found in 10%-20% of patients showing severe spermatogenesis disorders, including non-obstructive azoospermia. Methods: Literatures covering the relationship between male infertility and genetic disorders or chromosomal abnormalities were studied and summarized. Main findings Results: Genetic disorders, including Klinefelter syndrome, balanced reciprocal translocation, Robertsonian translocation, structural abnormalities in Y chromosome, XX male, azoospermic factor (AZF) deletions, and congenital bilateral absence of vas deferens were summarized and discussed from a practical point of view. Among them, understanding on AZF deletions significantly changed owing to advanced elucidation of their pathogenesis. Due to its technical progress, AZF deletion test can reveal their delicate variations and predict the condition of spermatogenesis. Thirty-nine candidate genes possibly responsible for azoospermia have been identified in the last 10 years owing to the advances in genome sequencing technologies. Conclusion: Genetic testing for chromosomes and AZF deletions should be examined in cases of severe oligozoospermia and azoospermia. Genetic counseling should be offered before and after genetic testing.

DOI： 10.1002/rmb2.12336

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Inflammatory cytokine markers, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-lymphocyte ratio, and platelet-to-lymphocyte ratio, play important roles as prognostic markers in several solid malignancies, including prostate cancer. We previously reported the NLR as a poor prognostic marker in bladder cancer, upper-urothelial carcinoma, adrenocortical carcinoma, penile cancer, and prostate cancer. This study examined the importance of the NLR as a prognostic marker for castration-resistant prostate cancer (CRPC) patients who received abiraterone acetate or enzalutamide. METHODS: A total of 805 prostate cancer patients developed in CRPC status were enrolled in this study. Of these patients, 449 received abiraterone acetate (ABI; 188 cases) or enzalutamide (ENZ; 261 cases) treatment, and the pre-treatment NLR values of these patients were obtained. We investigated the prognosis in those with higher and lower NLR values. RESULTS: The median NLR was 2.90, and a receiver operating characteristics analysis suggested a candidate cut-off point of 3.02. The median overall survival (OS) was 17.3 months in the higher NLR group (≥3.02) and 27.3 months in the lower NLR group (< 3.02) (p < 0.0001). This trend was also observed in both the ABI and ENZ groups (ABI: 29.3 vs. 15.1 months; ENZ: NR vs. 19.5 months; p < 0.0001 and < 0.0001, respectively). A multivariate analysis revealed that a higher NLR was an independent risk factor. The NLR value was thus shown to be correlated with the prostate cancer progression. CONCLUSIONS: A higher NLR was associated with a poorer OS for CRPC patients who received ABI or ENZ. The NLR was positively correlated with prostate cancer progression.

DOI： 10.1186/s12885-020-07410-2

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/bco2.46

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/bco2.46

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/bco2.43

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/bco2.43

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Metastatic spinal cord compression (MSCC) from prostate cancer (PC) influences not only patients' prognosis but also their quality of life. However, little is known about the clinical outcome of surgery for MSCC from PC. We evaluated both the oncological and functional outcomes of decompression and reconstruction surgery for patients with symptomatic MSCC from PC. METHODS: We assessed 19 patients who underwent decompression and reconstruction surgery for symptomatic MSCC from PC. Of these 19 patients, 8 had metastatic hormone-naïve PC (mHNPC) and 11 had metastatic castration-resistant PC (mCRPC). RESULTS: The median age of the patients with mHNPC and mCRPC was 72 and 65 years, respectively. The median prostate-specific antigen level at the time of diagnosis of MSCC in patients with mHNPC and mCRPC was 910 and 67 ng/mL, respectively. Although two of eight patients (25.0%) with mHNPC were ambulatory preoperatively, six patients (75.0%) were ambulatory postoperatively. Among 11 patients with mCRPC, only 3 (27.3%) were ambulatory preoperatively, while 6 (54.5%) were ambulatory postoperatively. The median postoperative overall survival among patients with mHNPC and mCRPC were not reached and 8 months, respectively. CONCLUSIONS: Decompression and reconstruction surgery for symptomatic MSCC from PC might contribute to a favorable functional outcome among men with mHNPC and mCRPC. However, its role in improving the oncological outcome remains unclear. The treatment strategy should be chosen by shared decision-making among patients, urologists, radiation oncologists, and orthopedic surgeons.

DOI： 10.1186/s12894-020-00713-3

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/bco2.42

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/bco2.42

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Some observational studies have implied a link between vasectomy and an elevated risk of prostate cancer. We investigated the impact of vasectomy on prostate cancer outgrowth, mainly using preclinical models. Neoplastic changes in the prostate were compared in transgenic TRAMP mice that underwent vasectomy vs. sham surgery performed at 4 weeks of age. One of the molecules identified by DNA microarray (i.e., ZKSCAN3) was then assessed in radical prostatectomy specimens and human prostate cancer lines. At 24 weeks, gross tumor (p = 0.089) and poorly differentiated adenocarcinoma (p = 0.036) occurred more often in vasectomized mice. Vasectomy significantly induced ZKSCAN3 expression in prostate tissues from C57BL/6 mice and prostate cancers from TRAMP mice. Immunohistochemistry showed increased ZKSCAN3 expression in adenocarcinoma vs. prostatic intraepithelial neoplasia (PIN), PIN vs. non-neoplastic prostate, Grade Group ≥3 vs. ≤2 tumors, pT3 vs. pT2 tumors, pN1 vs. pN0 tumors, and prostate cancer from patients with a history of vasectomy. Additionally, strong (2+/3+) ZKSCAN3 expression (p = 0.002), as an independent prognosticator, or vasectomy (p = 0.072) was associated with the risk of tumor recurrence. In prostate cancer lines, ZKSCAN3 silencing resulted in significant decreases in cell proliferation/migration/invasion. These findings suggest that there might be an association between vasectomy and the development and progression of prostate cancer, with up-regulation of ZKSCAN3 expression as a potential underlying mechanism.

DOI： 10.3390/cancers12082295

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/bco2.36

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/bco2.36

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Studies of prostate-specific antigen (PSA)-based population screening have been conducted in western countries, but there is little data in Asian populations. The objective of this study was to determine the efficacy of PSA screening in Asian men using real-world data over a period of 15 years after introducing population screening in Yokosuka City, Japan. METHODS: We investigated patients with pathologically diagnosed prostate cancer at four hospitals and two clinics across the Yokosuka area (Miura peninsula) between April 2001 and March 2015. Patients were divided into two groups; the S group consisted of those diagnosed by PSA-based population screening in Yokosuka City and the NS group consisted of those diagnosed by methods other than screening. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated using the Kaplan-Meier method with the log-rank test to compare survival between the two groups. Clinical and pathological factors for cancer-specific mortality were assessed with Cox regression analyses to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 3094 patients had been diagnosed with prostate cancer over the 15-year period. The median follow-up period was 77 months. The S group and the NS group consisted of 977 and 2117 patients, respectively. Patients in the S group were younger (age: 71 years vs 73 years, P < .001) and had a lower Charlson comorbidity index (CCI) with favorable oncological factors, such as lower initial PSA, Gleason score (GS), and risk category. Kaplan-Meier curves for OS and CSS revealed significant differences between the two groups (OS: P < .001, CSS: P < .001). Analysis with Cox proportional hazards model indicated the NS group (HR: 1.584, 95% CI, 1.065-2.356, P = .023), a CCI > 4 (HR: 1.552, 95% CI, 1.136-2.120, P = .006), a GS ≥ 8 (HR: 4.869, 95% CI, 2.631-9.001, P < .001), and nonlocalized cancer (locally advanced; HR: 2.632, 95% CI, 1.676-4.133, P < .001, advanced; HR: 9.468, 95% CI, 6.279-14.278, P < .001) as independent risk factors for cancer-specific mortality. CONCLUSIONS: PSA-based population screening of prostate cancer might be useful in the Japanese population.

DOI： 10.1002/pros.23997

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Although intravesical BCG immunotherapy has been the gold standard for non-surgical management of non-muscle-invasive bladder cancer (BC), a considerable number of patients exhibit resistance to the adjuvant treatment with unexplained mechanisms. This study aimed to investigate whether and how androgen receptor (AR) signals modulate BCG cytotoxicity in BC. AR knockdown or overexpression in BC lines resulted in induction or reduction, respectively, in intracellular BCG quantity and its cytotoxic activity. Microarray screening identified Rab27b, a small GTPase known to mediate bacterial exocytosis, which was up-regulated in BCG-resistant cells and down-regulated in AR-shRNA cells. Knockdown of Rab27b or its effector SYTL3, or overexpression of Rab27b also induced or reduced, respectively, BCG quantity and cytotoxicity. Additionally, treatment with GW4869, which was previously shown to inhibit Rab27b-dependent secretion, induced them and reduced Rab27b expression in BC cells. Meanwhile, AR expression was up-regulated in BCG-resistant lines, compared with respective controls. In a mouse orthotopic xenograft model, Rab27b/SYTL3 knockdown or GW4869 treatment enhanced the amount of BCG within tumors and its suppressive effect on tumor growth. Moreover, in non-muscle-invasive BC specimens from patients subsequently undergoing BCG therapy, positivity of AR/Rab27b expression was associated with significantly higher risks of tumor recurrence. AR activation thus correlates with resistance to BCG treatment, presumably via up-regulating Rab27b expression. Mechanistically, it is suggested that BCG elimination from urothelial cells is induced by Rab27b/SYTL3-mediated exocytosis. Accordingly, Rab27b inactivation, potentially via anti-androgenic drugs, and/or exocytosis inhibition are anticipated to sensitize the efficacy of BCG therapy, especially in patients with BCG-refractory AR/Rab27b-positive BC.

DOI： 10.1158/1535-7163.MCT-20-0050

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley-Blackwell Publishing Ltd  

DOI： 10.1002/ccr3.2817

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DOI： 10.1111/iju.14237

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Language：English  

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FLCN is a tumor suppressor gene which controls energy homeostasis through regulation of a variety of metabolic pathways including mitochondrial oxidative metabolism and autophagy. Birt-Hogg-Dubé (BHD) syndrome which is driven by germline alteration of the FLCN gene, predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas, pulmonary cysts and less frequently, salivary gland tumors. Here, we report metabolic roles for FLCN in the salivary gland as well as their clinical relevance. Screening of salivary glands of BHD patients using ultrasonography demonstrated increased cyst formation in the salivary gland. Salivary gland tumors that developed in BHD patients exhibited an upregulated mTOR-S6R pathway as well as increased GPNMB expression, which are characteristics of FLCN-deficient cells. Salivary gland-targeted Flcn knockout mice developed cytoplasmic clear cell formation in ductal cells with increased mitochondrial biogenesis, upregulated mTOR-S6K pathway, upregulated TFE3-GPNMB axis and upregulated lipid metabolism. Proteomic and metabolite analysis using LC/MS and GC/MS revealed that Flcn inactivation in salivary gland triggers metabolic reprogramming towards the pentose phosphate pathway which consequently upregulates nucleotide synthesis and redox regulation, further supporting that Flcn controls metabolic homeostasis in salivary gland. These data uncover important roles for FLCN in salivary gland; metabolic reprogramming under FLCN deficiency might increase nucleotide production which may feed FLCN-deficient salivary gland cells to trigger tumor initiation and progression, providing mechanistic insight into salivary gland tumorigenesis as well as a foundation for development of novel therapeutics for salivary gland tumors.

DOI： 10.1016/j.bbrc.2019.11.184

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Androgen receptor (AR) and estrogen receptor-β (ERβ) have been implicated in urothelial tumor outgrowth as promoters, while underlying mechanisms remain poorly understood. Our transcription factor profiling previously performed identified FOXO1 as a potential downstream target of AR in bladder cancer cells. We here investigated the functional role of FOXO1 in the development and progression of urothelial cancer in relation to AR and ERβ signals. In non-neoplastic urothelial SVHUC cells or bladder cancer lines, AR/ERβ expression or dihydrotestosterone/estradiol treatment reduced the expression levels of FOXO1 gene and induced those of a phosphorylated inactive form of FOXO1 (p-FOXO1). In chemical carcinogen-induced models, FOXO1 knockdown via shRNA or inhibitor treatment resulted in considerable induction of the neoplastic transformation of urothelial cells or bladder cancer development in mice. Similarly, FOXO1 inhibition considerably induced the viability, migration, and invasion of bladder cancer cells. Importantly, in FOXO1 knockdown sublines, an anti-androgen hydroxyflutamide or an anti-estrogen tamoxifen did not significantly inhibit the neoplastic transformation of urothelial cells, while dihydrotestosterone or estradiol did not significantly promote the proliferation or migration of urothelial cancer cells. In addition, immunohistochemistry in surgical specimens showed that FOXO1 and p-FOXO1 expression was down-regulated and up-regulated, respectively, in bladder tumor tissues, which was further associated with worse patient outcomes. AR or ERβ activation is thus found to correlate with inactivation of FOXO1 which appears to be their key downstream effector. Moreover, FOXO1, as a tumor suppressor, is likely inactivated in bladder cancer, which contributes in turn to inducing urothelial carcinogenesis and cancer growth.

DOI： 10.1530/ERC-20-0004

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Impact Journals LLC  

DOI： 10.18632/oncotarget.27719

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Background: The CHAARTED and LATITUDE trials demonstrated a prolonged overall survival (OS) for metastatic hormone-naïve prostate cancer (mHNPC) patients who receive up-front docetaxel or abiraterone acetate. These studies used their own risk criteria: CHAARTED trial defines high- and low-volume diseases and LATITUDE trial targeting a high-risk disease. The present study explored whether or not the CHAARTED and LATITUDE criteria were useful for predicting the outcome in Japanese bone mHNPC patients, including elderly patients (≥70 years). Methods: A total of 532 mHNPC patients diagnosed from 2004 to 2014 in multithird referral cancer centers were enrolled in this study. All patients had bone metastasis and received combined androgen blockade treatment as an initial hormonal therapy. Results: The number of patients with CHAARTED low-volume and high-volume diseases was 178 (33.5%) and 354 (66.5%), respectively. On the contrary, the number of patients with LATITUDE low-risk and high-risk diseases was 157 (29.5%) and 375 (70.5%), respectively. A total of 307 (57.7%) patients were defined as having both CHAARTED high-volume and LATITUDE high-risk disease. The median castration-resistant prostate cancer- (CRPC-) free survival was 12.5 months for the CHAARTED high volume, 56.9 months for the CHAARTED low volume, 13.6 months for the LATITUDE high risk, and 37.3 months for the LATITUDE low risk, respectively. The OS was 50.1 months in patients with CHAARTED high-volume disease, 95.1 months in patients with CHAARTED low-volume disease, 54.0 months in patients with LATITUDE high-risk disease, and 92.7 months in patients with LATITUDE low-risk disease, respectively. This trend was also observed in elderly (≥70 years old) patients. Conclusions: The patients with CHAARTED high-volume disease or LATITUDE high-risk disease showed a shorter CRPC-free survival and a shorter OS than those in the CHAARTED low-volume disease group or in the LATITUDE low-risk group among Asian Japanese bone metastatic HNPC patients.

DOI： 10.1155/2020/7804932

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000506675

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000508340

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000507280

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OBJECTIVES: To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. METHODS: A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. RESULTS: Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p < 0.001; intermediate-risk: p = 0.009; low-risk: p = 0.001), whereas significant differences were observed only in the intermediate-risk group (p = 0.003) within the RP vs BT group. CONCLUSION: The results of our propensity score analysis of mid-term localized prostate cancer treatment outcomes demonstrated no significant differences in the overall survival rate. Despite the difference in biochemical failure definition between surgery and radiotherapeutic approaches, the results of this study demonstrate improved biochemical control favoring IMRT and BT as compared to RP.

DOI： 10.1007/s00345-019-03056-3

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/iju.14101

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DOI： 10.1007/s00240-019-01171-9

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

DOI： 10.1007/s00240-019-01153-x

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000504700

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000504699

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Automated bone scan index (aBSI) change (ΔBSI) after treatment and survival in men with prostate cancer remains unclear. We evaluated the correlation between ΔBSI after cabazitaxel and overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (CRPC). METHODS: We retrospectively enrolled 32 men with bone metastatic CRPC who had received cabazitaxel. The correlation between ΔBSI from baseline to 16 weeks after starting cabazitaxel and OS was analyzed by multivariate analysis. RESULTS: Median age and time to CRPC were 70.7 years and 9.5 months, respectively. The median cycles of docetaxel before cabazitaxel were eight. Ten (31.2%) patients had visceral metastases at baseline. Median baseline prostate-specific antigen (PSA) was 123.0 ng/mL. The median aBSIs at baseline and 16 weeks after cabazitaxel were 3.2 and 4.4%, respectively. Improvements in aBSI and PSA after 16 weeks of cabazitaxel occurred in 7 (21.9%) and 12 patients (37.5%), respectively. There were no correlations between ΔBSI and OS (p = 0.55), but PSA change was significantly correlated with OS (p = 0.03) by multivariate analysis. CONCLUSIONS: This study demonstrated that ΔBSI from baseline to16 weeks after starting cabazitaxel was not correlated with OS among men with bone metastatic CRPC. Further prospective studies may be warranted to confirm the limited utility of aBSI in this setting.

DOI： 10.1159/000502655

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Introduction: Paraganglioma has been determined to be an extra-adrenal pheochromocytoma. Paraganglioma of the bladder is a rare entity, accounting for 0.06% of all bladder tumors. Case presentation: A 58-year-old woman had been annually followed up since being diagnosed with rectal cancer 5 years ago. In January 2018, follow-up computed tomography detected a bladder tumor, and she was referred to our department for a further examination. Cystoscopy revealed a submucosal tumor on her right bladder wall. We performed transurethral resection of the bladder tumor. When we first marked the tumor margin, the systolic blood pressure increased, so we abandoned resection. We performed meta-iodobenzylguanidine scintigraphy and acid urinary collection, neither of which revealed any abnormal findings. We therefore performed open partial cystectomy based on a clinical diagnosis of paraganglioma of the bladder. The pathological findings revealed paraganglioma of the bladder. Conclusion: We herein report a case of paraganglioma of the bladder.

DOI： 10.1002/iju5.12071

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000502174

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Language：Japanese   Publisher：(株)東京医学社  

ドナー特異的抗HLA抗体(HLA-DSA)陽性例の腎移植では、術後早期の急性抗体関連拒絶反応発症の危険性が高いため、術前に十分な脱感作療法を行い、術後免疫療法も強化する必要があるが、本邦では保険適用の問題から術前の脱感作療法には限界がある。今回、HLA-DSA陽性で、術前脱感作療法にリツキシマブを使用可能なABO式血液型不適合腎移植例に対して、術直後から抗ヒト胸腺細胞ウサギ免疫グロブリンを使用し良好な経過が得られた症例を経験したので、文献的考察を加えて報告した。

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DOI： 10.1159/000501849

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DOI： 10.1159/000501767

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Language：English  

Introduction: In June 2018, enzalutamide began to be sold in a tablet form in Japan and Germany. We herein report the case of an improvement in prostate cancer progression due to changing enzalutamide dosage form from a capsule to a tablet. Case presentation: A 76-year-old man was initially referred to our hospital for the further examination of his elevated prostate-specific antigen level (3664.0 ng/mL). He had developed castration-resistant prostate cancer 10 months after initial treatment. Treatment with enzalutamide (capsule form) was subsequently initiated. In June 2018, drug form of enzalutamide was changed from a capsule to a tablet. After switching to an enzalutamide tablet, his prostate-specific antigen level decreased significantly from 493.0 to 26.5 ng/mL. Conclusion: While the reason for this prostate-specific antigen response is unclear, changing the enzalutamide form from a capsule to a tablet may have improved the adherence of drug intake and thereby resulted in castration-resistant prostate cancer control.

DOI： 10.1002/iju5.12062

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Language：English  

Introduction: Iatrogenic ureteral injury is sometimes seen in daily clinical practice, and gynecological surgery carries the highest risk of ureteral injury among iatrogenic surgical ureteral injury. Case presentation: A 61-year-old woman was referred to our department for right ureteral stricture and hydronephrosis after total hysterectomy. We initially attempted ureteral stenting, but hydronephrosis redeveloped 1 month after ureteral stent removal. We performed ureteroscopy via an antegrade approach and successfully incised and dilated the ureter. Conclusion: We encountered a case of severe ureteral stenosis after total hysterectomy that was successfully treated endoscopically using ureteroscopy via an antegrade approach.

DOI： 10.1002/iju5.12061

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DOI： 10.1159/000501715

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DOI： 10.1159/000501716

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Language：Japanese   Publisher：(株)東京医学社  

当院で2012～2016年に生体腎移植を施行された末期腎不全患者70例を対象とし、先行的腎移植(PEKT)群18例と非PEKT群52例に分け、諸データの比較検討を行った。調査項目は「年齢」「性別」「小児例(18歳未満)の割合」「ABO血液型不適合例の割合」「抗ドナー特異的抗体陽性例の割合」「術後3ヵ月以内の急性拒絶反応」「移植1年後のeGFR」「1年プロトコール生検でのTMR」「1年生着率」などとした。検討の結果、「小児例の割合」がPEKT群で高い傾向にあり、他の項目に有意な群間差は認められなかった。

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BACKGROUND: We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab. METHODS: Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter ≥ 30% or not). RESULTS: There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3 ± 6.4, 115.5 ± 14.9, respectively. Lesions whose diameter decreased ≥30% at second assessment were defined as responding, and lesions whose diameter did not decrease ≥30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P = 0.025, OR: 13.087, 95%CI: 1.373-124.716). CONCLUSION: Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results. TRIAL REGISTRATION: Registered in University Hospital Medical Information Network in JAPAN [ UMIN0000008141 ], registration date: 11 Jun 2012.

DOI： 10.1186/s12885-019-5510-y

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1186/s12885-019-5512-9

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Other Link： http://link.springer.com/article/10.1186/s12885-019-5512-9/fulltext.html

Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English  

Introduction: Testicular epidermal cysts in Klinefelter syndrome are very rare. We report a case of Klinefelter syndrome associated with a testicular epidermal cyst. To our knowledge, this is the first report showing successful spermatozoa retrieval from the affected testis. Case presentation: A 25-year-old married man was referred to our hospital with right scrotal induration, which was in lower pole of the right testis. Testicular cancer tumor markers were normal; endocrinological findings indicated hypergonadotropic hypogonadism. Semen analyses revealed azoospermia. Preoperative chromosome test result: 47, XXY karyotype; ultrasonography report: 1.9-cm internal heterogeneous echoic mass in the right testis (malignancy not discarded). Because the patient hoped for children, he underwent high orchiectomy with ipsilateral testicular sperm extraction (200 spermatozoa from normal testicular tissue) for future fertilization procedures. Tumor pathology was an epidermal cyst. Conclusion: While performing orchiectomy for testicular tumors, sperm retrieval should be attempted from normal tissues in patients planning for children.

DOI： 10.1002/iju5.12037

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/iju.13841

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/iju.13841

Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：English  

Introduction: Although the tumors are often easily detected, a considerable number of patients with female urethral carcinoma are diagnosed in an advance stage. Thus, no evidence-based therapeutic approach has been established. We herein report our experience in the treatment of three female patients with urethral carcinoma. We also examined the expression of PD-L1 and CTLA-4. Case presentation: Three female patients pathologically diagnosed with urethral carcinoma, including urothelial carcinoma, squamous cell carcinoma, and adenocarcinoma, between 2013 and 2017 were analyzed in this study. Two patients underwent urethrectomy with cystostomy. Immunohistochemistry was performed to assess the levels of PD-L1 and CTLA-4 expression in patients with urethral carcinoma. Eleven control cases of urethral carcinoma tissue were also stained. Conclusion: This study revealed the expression of PD-L1 and CTLA-4 in female urethral carcinomas.

DOI： 10.1002/iju5.12029

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Introduction: The prognosis of type 2 papillary renal cell carcinoma is often poor. We herein report a case of papillary renal cell carcinoma with liver metastasis that was successfully treated with sorafenib as a second-line therapy. Case presentation: An 82-year-old man who had undergone radical nephrectomy 5 years previously experienced biopsy-proven liver metastasis. He received sunitinib as a first-line treatment; the dose was initially 12.5 mg/day and was escalated to 25 mg/day, but it was discontinued due to several adverse events. We then switched to sorafenib as a second-line treatment, which resulted in a partial response (51% reduction in tumor size); the patient showed no recurrence 5 months after the initiation of sorafenib treatment. An immunohistochemical analysis revealed the overexpression of Raf in both the primary and metastatic tumors. Conclusion: As sorafenib blocks Raf signaling, the expression of Raf may serve as a useful predictor of the efficacy of sorafenib.

DOI： 10.1002/iju5.12035

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Introduction: Clear cell adenocarcinoma of the prostatic urethra in men is an extremely rare disease, with only eight case reports published. Case presentation: A 56-year-old man visited our hospital for gross hematuria. Urinary cytology detected class V, cystoscopy showed no abnormal findings, and contrast-enhanced computed tomography also showed no abnormal findings in his upper urinary tract except for a low-enhancement lesion on his left prostate lobe. Magnetic resonance imaging revealed a cystic lesion surrounding the prostate that was suspected of being urethral or prostate cancer, so transurethral resection was performed. A papillary tumor was detected at the prostatic urethra, and after resecting this tumor, a cavity showing multiple tumors was observed. The final pathological diagnosis was clear cell adenocarcinoma. Laparoscopic radical cystectomy and urethrectomy were thus performed. The pathological diagnosis was the same as at the primary tumor site. Conclusion: We herein report a case of clear cell adenocarcinoma of the prostatic urethra.

DOI： 10.1002/iju5.12028

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Language：Japanese   Publisher：(一社)日本がん・生殖医療学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Bentham Science Publishers B.V.  

DOI： 10.2174/1874303X01912010001

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Introduction and Objectives: The neutrophil-to-lymphocyte ratio (NLR) has been suggested as a simple marker of the systemic inflammatory response in critical care patients. The NLR can be easily calculated from routine complete blood counts in the peripheral blood. This parameter has been reported to be an independent prognosticator for some solid malignancies. In the present study, we examined the importance of the NLR as a prognostic marker for castration-resistant prostate cancer (CRPC) patients who received docetaxel- (DOC-) based chemotherapy. Methods: We analyzed a total of 73 patients who received DOC chemotherapy for CRPC in Yokohama City University Medical Center and affiliated hospitals. Complete blood cell counts were performed, and the NLR was calculated using the neutrophil and lymphocyte counts obtained on the same day or a few days before the initiation of DOC chemotherapy. We determined the NLR cutoff value based on the sensitivity and specificity levels derived from area under the receiver operator characteristic curves for death. Results: The median overall survival (OS) after DOC was 21.0 months (range: 2.0-51.0). The median OS was shorter in patients with a high NLR (≥2.59) than in those with a low NLR (<2.59) (12.0 versus 31.6 months, p=0.001). In the multivariate analysis, the NLR and lymph node (LN) metastasis were independent predictors of the OS (hazard ratio 3.643, p=0.001; hazard ratio 2.184, p=0.038, respectively). Conclusions: The higher NLR group showed a significantly poorer OS than the lower NLR group. Pre-DOC NLR might be a new marker for predicting the prognosis of patients who receive DOC chemotherapy.

DOI： 10.1155/2019/2535270

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Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

<italic>Introduction</italic>. Nearly 80% of advanced prostate cancer patients respond to initial androgen deprivation therapy (ADT). However, ADT does not prevent the progression of prostate cancer over the long term, and the disease eventually progresses to castration-resistant prostate cancer (CRPC). Prior to the development of enzalutamide (ENZ) and abiraterone acetate, docetaxel was the only established treatment with life-prolongation for CRPC. ENZ is a second-generation anti-androgen receptor drug that has contributed to improving the prognosis of CRPC. Several studies have reported factors predicting the efficacy of ENZ; however, there are no confirmed biomarkers. The neutrophil-to-lymphocyte ratio (NLR) is an easily calculated biomarker that is associated with the prognosis of several solid malignancies. However, there were few studies investigated NLR for ENZ in patients with mCRPC. We examined the usefulness of the NLR as a predictive tool for ENZ.<italic> Methods</italic>. We retrospectively examined a total of 106 CRPC patients who were treated with ENZ until September 2016 in Yokohama City University Hospital, Yokohama City University Medical Center, and National Cancer Center Hospital East. ENZ was routinely started as a dose of 160 mg per day; the dosage was reduced in some patients due to side effects. Drug holiday for 1-2 weeks or dose reduction to 80-120mg was done and no patients discontinued ENZ treatment due to adverse effects. ENZ was stopped when cancer progression was detected based on PSA elevation, radiographic findings, and deterioration of the patient’s performance status. The cut-off NLRs for overall survival (OS) and cancer-specific survival (CSS) were determined based on the receiver-operator curves. Kaplan-Meier curves were used to analyze the factors associated with OS or CSS and a log-rank test was performed. A multivariate analysis was also performed to analyze the factors associated with the prognosis.<italic> Results</italic>. We retrospectively reviewed 106 consecutive CRPC patients who were both treated with ENZ and were able to be counted before ENZ NLR. Cut-off point was 2.14 for both OS and CSS by receiver operator characteristic curve. The patients were then divided into the higher NLR group (≥2.14) and lower NLR group (&lt;2.14). Multivariate analysis showed that NLR and predocetaxel chemotherapy were independent risk factors for both overall and cancer-specific survival.<italic> Conclusions</italic>. The NLR might be a useful biomarker for predicting the prognosis of mCRPC patients who are treated with ENZ.

DOI： 10.1155/2019/9450838

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Other Link： http://downloads.hindawi.com/journals/bmri/2019/9450838.xml

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INTRODUCTION: Nivolumab has been introduced for metastatic renal cell carcinoma (mRCC) as a second-line therapy for years. However, despite widespread evidence of its utility, few reports have described the efficacy of nivolumab for mRCC patients on hemodialysis. CASE PRESENTATION: A 68-year-old man with a 20-year history of dialysis due to chronic glomerulotubular nephritis was referred to our department for bilateral renal tumors in 2015. In February 2015, contrast-enhanced CT revealed findings suggestive of RCC, so we performed right nephrectomy. The pathological diagnosis was clear cell carcinoma and papillary renal cell carcinoma. In July 2015, we consequently performed left nephrectomy, and the pathological diagnosis was metastatic RCC. In February 2016, because follow-up CT revealed a right adrenal tumor with time-dependent growth, sunitinib (25 mg/body) was introduced. In January 2017, although sunitinib had controlled the adrenal metastasis for 9 courses (11 months), liver metastasis was observed, so nivolumab was introduced as a second-line chemotherapy in March 2017. Nivolumab was able to control the mRCC for 15 months (32 courses). While CT showed no metastatic sites except for the liver and adrenal glands, his general condition gradually decreased, and he died in October 2018. CONCLUSION: We herein report a patient with RCC on hemodialysis with long-term cancer control by nivolumab.

DOI： 10.1159/000501768

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Dysgeusia is an adverse effect caused by enzalutamide said to affect 1-5% of patients. The reported management strategies include a temporary drug holiday, the prescription of herbal medicine, and changing the timing of enzalutamide intake from morning to before sleep at night. Case 1: A 72-year-old man developed castration-resistant prostate cancer (CRPC) and was administered enzalutamide. After six weeks of enzalutamide installation, he showed taste alternation, and consequently his dysgeusia increased to grade 2; we therefore changed the medicine intake time from morning to night just before sleep without dose reduction. Four weeks after changing the timing, his dysgeusia had improved. Case 2: A 63-year-old man had developed bone metastatic CRPC, so the combination of Ra-223 and enzalutamide (160 mg/body) was introduced. His serum PSA level had gradually decreased, but dysgeusia appeared, so we changed the timing of enzalutamide intake from morning to night just before sleep without dose reduction. One month after changing the timing, his dysgeusia had improved. We herein report two cases of enzalutamide-induced dysgeusia successfully treated by changing the timing of drug intake from morning intake to just before sleep.

DOI： 10.1159/000502054

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GnRH antagonist and GnRH agonist are widely used as androgen deprivation therapy for metastatic prostate cancer. A previous report demonstrated that patients with PSA levels of >20 ng/mL using GnRH antagonists showed favorable outcomes in comparison to those using GnRH agonists. An 82-year old male patient with edema, a stony hard nodule on his prostate, and an initial PSA level of 6,717 ng/mL was referred to our hospital due to suspected prostate cancer. He received prostate needle biopsy and was diagnosed with prostate cancer with bone metastasis, with a Gleason Score of 4 + 4 = 8. He was then treated with a GnRH agonist (leuprorelin acetate) and bicalutamide from July 2015. Although his PSA level decreased to 582.0 ng/mL in December 2015, his PSA level gradually increased and CRPC developed. He indicated that he did not wish to take 2nd generation anti-androgen drugs or receive systemic chemotherapy. We introduced a GnRH antagonist (degarelix) in February 2015; his PSA level did not change and his CRPC was controlled. We herein report a case in which changing a GnRH agonist to a GnRH antagonist contributed to CRPC control.

DOI： 10.1159/000502859

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. METHODS: We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. RESULTS: There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001). CONCLUSIONS: PD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.

DOI： 10.1186/s12894-018-0414-8

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：Japanese   Publisher：日本老年泌尿器科学会  

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Language：Japanese   Publisher：日本老年泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Baskent University  

Objectives: Because of recent developments in im - munosuppressive therapy, renal transplant outcomes have improved. Although reports on the association between immunosuppressive therapy and malignant disease are available, the results are controversial. The neutrophil-to-lymphocyte ratio has been reported as an easy tumor marker for predicting the prognoses of some solid tumors. In the present study, we examined changes in neutrophil-to-lymphocyte ratio after renal transplant and discussed cases in which malignant disease developed after renal transplant. Materials and Methods: Our study included 137 patients who underwent renal transplant between August 2001 and September 2015. Four of these patients (2.9%) developed malignant disease. The neutrophil-tolymphocyte ratio was calculated based on the numbers of neutrophils and lymphocytes in the complete blood count and evaluated before and at 1, 3, 6, and 12 months and at 3 years after renal transplant. Results: The neutrophil-to-lymphocyte ratio was markedly high at 1 week and 1 month after renal transplant and gradually decreased until it became stable at 3 months posttransplant. In patients with malignant disease, there was a gradual increase in the neutrophil-to-Iymphocyte ratio after renal transplant. Conclusions: We observed dramatic differences in the neutrophil-to-lymphocyte ratio at 1 and 3 months after renal transplant. The neutrophil-to-lymphocyte ratio of patients with malignant disease after renal transplant continued to increase.

DOI： 10.6002/ect.2017.0098

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Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000493324

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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DOI： 10.1159/000492779

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Language：English   Publishing type：Research paper (scientific journal)  

Oxidative stress is a primary cause of vascular endothelial damage. In the prostate, ischemia increases the levels of reactive oxygen species, growth factors and cytokines, and induces the development of angiogenesis, which results in cancer progression. The expression levels of an oxidative stress marker, 8-hydroxyguanosine (8-OHdG), were compared between prostate cancer and non-neoplastic prostate tissues. A prostate tissue microarray composed of 10 cases of prostatic adenocarcinoma and 70 cases of benign prostatic hyperplasia was immunohistochemically stained for 8-OHdG. All cases expressed 8-OHdG. The levels of 8-OHdG expression in prostatic cancer (30.0% moderate and 70.0% strong) were significantly higher than those in benign prostatic hyperplasia (71.4% moderate and 28.6% strong; (p<0.01). Notably, 8-OHdG is expressed more highly in prostate cancer tissues in comparison to benign prostate tissues.

DOI： 10.3892/mco.2018.1665

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Language：Japanese   Publisher：(一社)日本移植学会  

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Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer, which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming toward upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics that are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.

DOI： 10.1093/hmg/ddy181

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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DOI： 10.1111/iju.13756

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：日本小児泌尿器科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Because of recent developments in immunosuppressive therapy, renal transplant outcomes have improved. Although reports on the association between immunosuppressive therapy and malignant disease are available, the results are controversial. The neutrophil-to-lymphocyte ratio has been reported as an easy tumor marker for predicting the prognoses of some solid tumors. In the present study, we examined changes in neutrophil-to-lymphocyte ratio after renal transplant and discussed cases in which malignant disease developed after renal transplant. MATERIALS AND METHODS: Our study included 137 patients who underwent renal transplant between August 2001 and September 2015. Four of these patients (2.9%) developed malignant disease. The neutrophil-to-lymphocyte ratio was calculated based on the numbers of neutrophils and lymphocytes in the complete blood count and evaluated before and at 1, 3, 6, and 12 months and at 3 years after renal transplant. RESULTS: The neutrophil-to-lymphocyte ratio was markedly high at 1 week and 1 month after renal transplant and gradually decreased until it became stable at 3 months posttransplant. In patients with malignant disease, there was a gradual increase in the neutrophil-to-Iymphocyte ratio after renal transplant. CONCLUSIONS: We observed dramatic differences in the neutrophil-to-lymphocyte ratio at 1 and 3 months after renal transplant. The neutrophil-to-lymphocyte ratio of patients with malignant disease after renal transplant continued to increase.

DOI： 10.6002/ect.2017.0098

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Language：Japanese   Publisher：日本小児泌尿器科学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s12894-018-0346-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s12885-018-4401-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

DOI： 10.3892/ol.2018.8351

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc  

DOI： 10.1016/j.eucr.2018.03.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc  

DOI： 10.1016/j.eucr.2018.02.017

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Language：Japanese   Publisher：腎移植・血管外科研究会  

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Language：Japanese   Publisher：腎移植・血管外科研究会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc.  

DOI： 10.1016/j.clgc.2017.09.008

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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PURPOSE: We investigated prospectively whether 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) can predict the overall survival (OS) of patients with advanced renal cell carcinoma (RCC) previously treated by molecular targeted therapies. METHODS: Between 2009 and 2016, 81 patients who had received single molecular targeted therapies (43 sorafenib, 27 sunitinib, 8 temsirolimus and others) and were scheduled for second line molecular targeted therapies for advanced RCC were enrolled in this prospective study. FDG PET/CT was performed after first line molecular targeted therapies, the max SUVmax (highest standardized uptake value for each patient) recorded, and its association with OS compared with those of known risk factors. The median follow-up was 15.4 months (range 0.9-97.4 months). RESULTS: The max SUVmax of the 81 subjects ranged from undetectable to 23.0 (median 7.1). Patients with high max SUVmax had a poor prognosis and multivariate analysis with established risk factors showed that it was an independent predictor of survival (p < 0.001; hazard ratio 1.156; 95% confidence interval 1.080-1.239). Subclassification of patients by max SUVmax showed that the median OS of patients with max SUVmax < 7.0 (39), 7.0-12.0 (30), and ≥ 12.0 (12) were 32.8, 15.2, and 6.0 months, respectively. These differences are statistically significant (< 7.0 versus 7.0-12.0: p = 0.0333, 7.0-12.0 versus ≥ 12.0: p = 0.0235). CONCLUSIONS: The max SUVmax by FDG PET/CT of patients with RCC evaluated after their first molecular targeted therapy predicts OS. FDG PET/CT is a useful "imaging biomarker" for patients with advanced RCC planning sequential molecular targeted therapies.

DOI： 10.1007/s00280-018-3542-7

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Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

DOI： 10.3892/mco.2018.1573

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Using preclinical models, we have recently found that ELK1, a transcriptional factor that activates downstream targets, including c-fos proto-oncogene, induces bladder cancer outgrowth. Here, we immunohistochemically determined the expression status of phospho-ELK1, an activated form of ELK1, in upper urinary tract urothelial carcinoma (UUTUC). Overall, phospho-ELK1 was positive in 47 (47.5%; 37 weak (1+) and 10 moderate (2+)) of 99 UUTUCs, which was significantly (P = 0.002) higher than in benign urothelium (21 (25.3%) of 83; 17 1+ and 4 2+) and was also associated with androgen receptor expression (P = 0.001). Thirteen (35.1%) of 37 non-muscle-invasive versus 34 (54.8%) of 62 muscle-invasive UUTUCs (P = 0.065) were immunoreactive for phospho-ELK1. Lymphovascular invasion was significantly (P = 0.014) more often seen in phospho-ELK1(2+) tumors (80.0%) than in phospho-ELK1(0/1+) tumors (36.0%). There were no statistically significant associations between phospho-ELK1 expression and tumor grade, presence of concurrent carcinoma in situ or hydronephrosis, or pN status. Kaplan-Meier and log-rank tests revealed that patients with phospho-ELK1(2+) tumor had marginally and significantly higher risks of disease progression (P = 0.055) and cancer-specific mortality (P = 0.008), respectively, compared to those with phospho-ELK1(0/1+) tumor. The current results thus support our previous observations in bladder cancer and further suggest that phospho-ELK1 overexpression serves as a predictor of poor prognosis in patients with UUTUC.

DOI： 10.3390/ijms19030777

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc  

DOI： 10.1016/j.eucr.2018.02.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Korean Society for Reproductive Medicine  

DOI： 10.5653/cerm.2018.45.1.48

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Korean Society for Reproductive Medicine  

DOI： 10.5653/cerm.2018.45.1.44

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s13256-017-1558-y

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DOI： 10.3892/mco.2017.1537

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Lenalidomide has been developed as the derivative of thalidomide that has fewer side effects. We herein report a rare case of castration-resistant prostate cancer successfully maintained using lenalidomide for multiple myeloma.

DOI： 10.1002/ccr3.1328

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000487588

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000487389

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000487390

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

DOI： 10.1007/s00432-017-2520-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc  

DOI： 10.1016/j.eucr.2017.11.007

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BACKGROUND: We investigated the role of prostaglandin receptors (e.g. prostaglandin E2 receptor 2 (EP2), EP4) and the efficacy of celecoxib in urothelial tumourigenesis and cancer progression. METHODS: We performed immunohistochemistry in bladder cancer (BC) tissue microarrays, in vitro transformation assay in a normal urothelial SVHUC line, and western blot/reverse transcription-polymerase chain reaction/cell growth assays in BC lines. RESULTS: EP2/EP4 expression was elevated in BCs compared with non-neoplastic urothelial tissues and in BCs from those who were resistant to cisplatin-based neoadjuvant chemotherapy. Strong positivity of EP2/EP4 in non-muscle-invasive tumours or positivity of EP2/EP4 in muscle-invasive tumours strongly correlated with disease progression or disease-specific mortality, respectively. In SVHUC cells, exposure to a chemical carcinogen 3-methylcholanthrene considerably increased and decreased the expression of EP2/EP4 and phosphatase and tensin homologue (PTEN), respectively. Treatment with selective EP2/EP4 antagonist or celecoxib also resulted in prevention in 3-methylcholanthrene-induced neoplastic transformation of SVHUC cells. In BC lines, EP2/EP4 antagonists and celecoxib effectively inhibited cell viability and migration, as well as augmented PTEN expression. Furthermore, these drugs enhanced the cytotoxic activity of cisplatin in BC cells. EP2/EP4 and PTEN were also elevated and reduced, respectively, in cisplatin-resistant BC sublines. CONCLUSIONS: EP2/EP4 activation correlates with induction of urothelial cancer initiation and outgrowth, as well as chemoresistance, presumably via downregulating PTEN expression.

DOI： 10.1038/bjc.2017.393

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Introduction: Horseshoe kidney is one of the most common congenital renal fusion anomalies. Due to its poor mobility and abnormal vasculature form, surgeons should pay close attention to all anatomical variations. Case Presentation: An 83-year-old woman was referred to our hospital because of left renal tumor in a horseshoe kidney incidentally found by her previous hospital. We performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell renal cell carcinoma. G2 INFα V-pT1a with a negative surgical margin. No evidence of recurrence has been noted, and the renal function is well preserved at 28 months after surgery. Conclusion: When performing laparoscopic partial nephrectomy for renal carcinoma, especially a horseshoe kidney, preoperative imaging is crucial for identifying the location of the renal vessels.

DOI： 10.1155/2018/7135180

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

DOI： 10.1155/2018/8796327

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This study aimed to develop a prediction model for the operative time of flexible ureteroscopy (fURS) for renal stones. We retrospectively evaluated patients with renal stones who had been treated successfully and had stone-free status determined by non-contrast computed tomography (NCCT) 3 months after fURS and holmium laser lithotripsy between December 2009 and September 2014 at a single institute. Correlations between possible factors and the operative time were analyzed using Spearman's correlation coefficients and a multivariate linear regression model. The P value < 0.1 was used for entry of variables into the model and for keeping the variables in the model. Internal validation was performed using 10,000 bootstrap resamples. Flexible URS was performed in 472 patients, and 316 patients were considered to have stone-free status and were enrolled in this study. Spearman's correlation coefficients showed a significant positive relationship between the operation time and stone volume (ρ = 0.417, p < 0.001), and between the operation time and maximum Hounsfield units (ρ = 0.323, p < 0.001). A multivariate assessment with forced entry and stepwise selection revealed six factors to predict the operative time of fURS: preoperative stenting, stone volume, maximum Hounsfield unit, surgeon experience, sex, and sheath diameter. Based on this finding, we developed a model to predict operative time of fURS. The coefficient of determination (R2) in this model was 0.319; the mean R2 value for the prediction model was 0.320 ± 0.049. To our knowledge, this is the first report of a model for predicting the operative time of fURS treatment of renal stones. The model may be used to reliably predict operative time preoperatively based on patient characteristics and the surgeons' experience, plan staged URS, and avoid surgical complications.

DOI： 10.1371/journal.pone.0192597

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

DOI： 10.1155/2018/4526721

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We have recently demonstrated that ELK1, a transcription factor that triggers downstream targets including c-Fos proto-oncogene, promotes the growth of bladder cancer cells possessing a functional androgen receptor (AR). We here assessed the function of ELK1, as well as the efficacy of a selective α1A-adrenergic blocker silodosin that has been shown to inhibit ELK1 activity in bladder cancer cells, in urothelial tumorigenesis. The level of ELK1 expression in an immortalized normal urothelial cell line SVHUC stably expressing wild-type AR (SVHUC-AR) was considerably higher than that in AR-negative SVHUC-vector cells, which was induced further or reduced by dihydrotestosterone or silodosin treatment, respectively. In SVHUC-AR cells exposed to a chemical carcinogen 3-methylcholanthrene, silodosin significantly reduced the expression levels of oncogenes (e.g. c-Fos, Jun, Myc), as well as phospho-p38 MAPK and phospho-ERK proteins, and increased those of tumor suppressor genes (e.g. p53, PTEN, UGT1A). ELK1 suppression via ELK1-short hairpin RNA virus infection or silodosin treatment also resulted in significant inhibition in 3-methylcholanthrene-induced neoplastic transformation of SVHUC-AR cells, but not that of SVHUC-vector cells. In N-butyl-N-(4-hydroxybutyl)nitrosamine-treated male C57BL/6 mice, the incidence rate of bladder tumors was significantly (P = 0.007) lower in the silodosin group than in the control group. ELK1 thus appears to play a critical role in urothelial tumorigenesis, and silodosin prevents it presumably via down-regulation of ELK1. Moreover, ELK1 may require an activated AR for inducing neoplastic transformation of urothelial cells. Our findings may therefore offer a novel chemopreventive approach, via ELK1 inactivation using silodosin treatment, for bladder cancer.

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DOI： 10.1016/j.clgc.2017.07.016

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OBJECTIVE: Urethral stenosis is a disease in which the lumen of the urethra becomes constricted by fibrosis. Such stenoses have been treated by urethral dilation using a bougie and optical internal urethrotomy (OIU). Recently, high-pressure balloon dilation (BD) has been developed as a new treatment method for urethral stenosis. The present study compared the effectiveness of urethral dilation by BD and OIU. METHODS: Twenty-two patients of urethral stenosis were treated at Yokohama City University Medical Center between 2005 and 2015. Of these, 13 underwent BD, whereas OIU was performed in 9. BD was performed at 30 atm twice for 5 min each time. In OIU, an endoscopic knife was used to cut out the stenotic lesion in 3 directions. The endpoint was set as restenosis, which required additional surgical treatment, including BD, OIU, and the use of a urethral bougie. RESULTS: The causes of urethral stricture were endoscopic surgery (n = 7; 31.8%), development after total prostatectomy (n = 4; 18.2%), iatrogenic reasons associated with catheter insertion (n = 5; 22.7%), development after a prostate needle biopsy (n = 3; 13.6%), and unknown (n = 3; 13.6%). The site of the stenotic lesion site was the anastomosis (n = 3; 13.6%), bladder neck (n = 6; 27.3%), prostatic urethra (n = 4; 18.2%), anterior urethra (n = 7; 31.8%), and membranous urethra (n = 2; 9.1%). The stenosis-free rate was 84% for those undergoing BD and 22% for those receiving OIU. The median stenosis-free time was significantly longer after BD than OIU (1675 vs. 244 days, respectively; P < .01). CONCLUSION: The stenosis-free time was significantly longer after BD than OIU.

DOI： 10.1111/luts.12208

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DOI： 10.1186/s13256-017-1473-2

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BACKGROUND: Primary large cell neuroendocrine carcinoma of the kidney is a rare and generally very aggressive disease. We present a case of a patient with primary large cell neuroendocrine carcinoma of the kidney with cardiac metastasis. CASE PRESENTATION: A 59-year-old Japanese man presented to his previous physician with hematuria. Computed tomography revealed masses in the heart and right kidney, and fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the heart. A cardiac biopsy under transesophageal echocardiographic guidance revealed a metastatic tumor. Subsequently, multiple lung lesions were detected, and a right nephrectomy was performed after these metastases were suspected to have originated from renal carcinoma. Large cell neuroendocrine carcinoma of the kidney was ultimately diagnosed. Pancreatic metastasis was detected on computed tomography postoperatively. Three courses of chemotherapy with carboplatin and irinotecan were administered, and were temporarily effective against the metastatic lesions in the lungs and pancreas. However, our patient's general condition deteriorated with the progression of the lesions, and he died 9 months after his initial examination. CONCLUSIONS: Multi-agent chemotherapy, including platinum-based drugs was effective against large cell neuroendocrine carcinoma metastases, albeit only temporarily. This is the first reported case of large cell neuroendocrine carcinoma with cardiac metastasis.

DOI： 10.1186/s13256-017-1460-7

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Editorial Board of Acta Urologica Japonica  

DOI： 10.14989/ActaUrolJap-63-10-407

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Ltd  

DOI： 10.1002/rmb2.12052

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ediciones Doyma, S.L.  

DOI： 10.1016/j.androl.2017.09.001

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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DOI： 10.1016/j.urolonc.2017.05.019

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：腎移植・血管外科研究会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s12894-017-0279-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s13256-017-1379-z

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Language：English   Publisher：S. Karger AG  

DOI： 10.1159/000447175

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OBJECTIVE: More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. MATERIALS AND METHODS: The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. RESULTS: In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). CONCLUSION: PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer.

DOI： 10.1080/21681805.2017.1298155

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Language：Japanese   Publisher：医学図書出版(株)  

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DOI： 10.1016/j.clgc.2016.12.020

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s13256-017-1372-6

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Language：English   Publisher：S. Karger AG  

DOI： 10.1159/000447162

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Editorial Board of Acta Urologica Japonica  

DOI： 10.14989/ActaUrolJap-63-7-271

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Language：Japanese   Publisher：泌尿器科紀要刊行会  

症例1は52歳女で、18歳時より両側の膀胱尿管逆流症(VUR)が指摘され、有熱性尿路感染(fUTI)を反復し、プロピベリン内服後も右側VURが残存した。症例2は29歳女で、23歳時にfUTIを発症し、右腎萎縮と右III度のVURを認め、プロピベリン内服後もfUTIを反復した。症例3は40歳女で、25歳時よりfUTIを反復し、徐々に抗生剤に不応となり排尿時膀胱尿道撮影(VCUG)にてVURと膀胱容量の低下を認め、プロピベリン内服後もfUTIを反復した。各症例とも経尿道的Deflux注入療法を施行した結果、術後合併症なく経過しプロピベリン内服は中止となり、術後6ヵ月のVCUGにて逆流消失を確認した。症例1、2は4年9ヵ月～5年1ヵ月経過してfUTIの発症は認めない。症例3は術後2年3ヵ月にfUTIを発症し、ウラピジル内服開始となった。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01269&link_issn=&doc_id=20170810460004&doc_link_id=1390290699820953984&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390290699820953984&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

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DOI： 10.1016/j.androl.2016.08.002

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s13256-017-1319-y

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Language：Japanese   Publisher：日本小児泌尿器科学会  

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DOI： 10.1186/s12894-017-0240-4

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DOI： 10.1080/19396368.2017.1294214

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Language：Japanese   Publisher：日本小児泌尿器科学会  

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DOI： 10.1016/j.tranon.2017.01.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s13256-017-1303-6

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DOI： 10.5489/cuaj.4192

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Language：Japanese   Publisher：医学図書出版(株)  

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PURPOSE: We evaluated 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) results as outcome predictors for patients with metastatic renal cell carcinoma (RCC) treated by everolimus (EVL), an inhibitor of mammalian target of rapamycin. METHODS: We retrospectively reviewed 30 patients who were treated with EVL for metastatic RCC between May 2010 and March 2015, by evaluating their FDG PET/CT result before and 1 month after starting EVL treatment. We examined the relationships between each patient's maximum standardized uptake value (max SUVmax) assessed by FDG PET/CT on progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS for all 30 patients was 3.77 months (range 0.72-24.56 months) and median OS after EVL treatment of all 30 patients was 11.67 months (range 1.0-62.98 months). Enrolled patients were divided into two groups by max SUVmax prior to EVL (median = 7.6) and at 1 month after EVL treatment (median = 5.7). PFS were significantly shorter in higher max SUVmax prior to EVL (<7.6, PFS 7.8 vs 3.5 months, log-rank P = 0.017) and at 1 month after EVL (<5.7, PFS 10.6 vs 2.7 months, log-rank P = 0.002) than lower max SUVmax. OS were also significantly shorter in higher max SUVmax prior to EVL (<7.6, OS 18.1 vs 7.5 months, log-rank P = 0.010) and at 1 month after EVL (<5.7, OS 17.2 vs 7.5 months, log-rank P = 0.009) than lower max SUVmax. Multivariate Cox hazard regression analysis indicated that max SUVmax at 1 month after EVL is an independent predictor of both PFS and OS in patients treated with EVL although univariate regression analysis showed max SUVmax before EVL is a possible predictor. CONCLUSIONS: Max SUVmax assessed by FDG PET/CT prior to EVL and at 1 month after EVL treatment can accurately predict PFS and can guide decisions on whether to continue or change treatments for patients with EVL-treated RCC who suffer from adverse events.

DOI： 10.1007/s00280-017-3275-z

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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DOI： 10.1016/j.clgc.2016.07.026

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DOI： 10.1016/j.juro.2017.02.2264

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DOI： 10.1111/iju.13316

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English   Publishing type：Research paper (scientific journal)  

Germline H255Y and K508R missense mutations in the folliculin (FLCN) gene have been identified in patients with bilateral multifocal (BMF) kidney tumours and clinical manifestations of Birt-Hogg-Dubé (BHD) syndrome, or with BMF kidney tumours as the only manifestation; however, their impact on FLCN function remains to be determined. In order to determine if FLCN H255Y and K508R missense mutations promote aberrant kidney cell proliferation leading to pathogenicity, we generated mouse models expressing these mutants using BAC recombineering technology and investigated their ability to rescue the multi-cystic phenotype of Flcn-deficient mouse kidneys. Flcn H255Y mutant transgene expression in kidney-targeted Flcn knockout mice did not rescue the multi-cystic kidney phenotype. However, expression of the Flcn K508R mutant transgene partially, but not completely, abrogated the phenotype. Notably, expression of the Flcn K508R mutant transgene in heterozygous Flcn knockout mice resulted in development of multi-cystic kidneys and cardiac hypertrophy in some mice. These results demonstrate that both FLCN H255Y and K508R missense mutations promote aberrant kidney cell proliferation, but to different degrees. Based on the phenotypes of our preclinical models, the FLCN H255Y mutant protein has lost it tumour suppressive function leading to the clinical manifestations of BHD, whereas the FLCN K508R mutant protein may have a dominant negative effect on the function of wild-type FLCN in regulating kidney cell proliferation and, therefore, act as an oncoprotein. These findings may provide mechanistic insight into the role of FLCN in regulating kidney cell proliferation and facilitate the development of novel therapeutics for FLCN-deficient kidney cancer.

DOI： 10.1093/hmg/ddw392

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：医学図書出版(株)  

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DOI： 10.1155/2017/7981549

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DOI： 10.1159/000477131

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DOI： 10.1155/2017/7538647

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

DOI： 10.1016/j.ijscr.2017.06.047

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

DOI： 10.1155/2017/2392670

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

DOI： 10.1016/j.ijscr.2017.02.003

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DOI： 10.1016/j.ijscr.2016.11.042

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DOI： 10.1155/2017/9341042

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DOI： 10.1186/s12885-016-2979-5

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BACKGROUND: Ureteral stenting has been a fundamental part of various urological procedures. Selecting a ureteral stent of optimal length is important for decreasing the incidence of stent migration and complications. The aim of the present study was to develop and internally validate a model for predicting the ureteral length for ureteral stent insertion. METHODS: This study included a total of 127 patients whose ureters had previously been assessed by both intravenous urography (IVU) and CT scan. The actual ureteral length was determined by direct measurement using a 5-Fr ureteral catheter. Multiple linear regression analysis with backward selection was used to model the relationship between the factors analyzed and actual ureteral length. Bootstrapping was used to internally validate the predictive model. RESULTS: Patients all of whom had stone disease included 76 men (59.8%) and 51 women (40.2%), with the median and mean (± SD) ages of 60 and 58.7 (±14.2) years. In these patients, 53 (41.7%) right and 74 (58.3%) left ureters were analyzed. The median and mean (± SD) actual ureteral lengths were 24.0 and 23.3 (±2.0) cm, respectively. Using the bootstrap methods for internal validation, the correlation coefficient (R2) was 0.57 ± 0.07. CONCLUSION: We have developed a predictive model, for the first time, which predicts ureteral length using the following five preoperative characteristics: age, side, sex, IVU measurement, and CT calculation. This predictive model can be used to reliably predict ureteral length based on clinical and radiological factors and may thus be a useful tool to help determining the optimal length of ureteral stent.

DOI： 10.1186/s12894-016-0189-8

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/jjco/hyw110

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s13104-016-2279-9

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DOI： 10.1016/j.urolonc.2016.05.016

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000453448

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000449372

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Language：Japanese   Publisher：(一社)日本移植学会  

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DOI： 10.18632/oncotarget.10679

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DOI： 10.1111/iju.13124

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Language：Japanese   Publisher：医学図書出版(株)  

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DOI： 10.1016/j.clgc.2015.11.013

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DOI： 10.18632/oncotarget.9994

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

DOI： 10.1186/s12885-016-2443-6

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Editorial Board of Acta Urologica Japonica  

DOI： 10.14989/ActaUrolJap-62-7-361

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：泌尿器科紀要刊行会  

症例1(75歳男性)。進行膀胱癌に対する術前化学療法としてGC療法(gemcitabine+CDDP)を開始したところ、第8病日目より高度な低Na血症を呈した。一方、Na排泄亢進も認められたが、腎機能障害は認めず、甲状腺ホルモン、コルチゾール値は正常値で、ADHは測定感度以下であったことから、SIADHと診断された。以後、生理食塩水とNaCl製剤による補正を行った結果、第10病日目に低Na血症が改善後、2コース目よりはgemcitabine+nedaplatin療法へ変更し、3コース目まで施行後、膀胱全摘術を行った。症例2(54歳男性)。陰茎癌に対する術前化学療法としてTPF療法(CDDP+paclitaxel+fluorouracil)を施行したところ、第7病日目に高度な低Na血症を呈した。起立性低血圧、腎機能低下などの脱水所見とNa排泄亢進を認めたことから、RSWSと診断された。以後、Na補充と脱水補正を開始した結果、第11病日目に全身状態は改善、2コース目よりはCDDPを減量したが低Na血症の再現はなく、3コース目まで施行後、陰茎部分切除術+鼠径リンパ節郭清術を施行した。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J01269&link_issn=&doc_id=20160824420004&doc_link_id=1390290699733438976&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390290699733438976&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Osteoporosis is a common consequence of androgen deprivation therapy (ADT) for prostate cancer. Up to 20 % of men on ADT have suffered from fractures within 5 years. The WHO Fracture Risk Assessment Tool (FRAX) has been utilized to predict the 10-year probability of major osteoporotic and hip fracture. However, to date, no large studies assessing the utility of the FRAX score in prostate cancer patients with or without ADT have been performed. We herein evaluated the impact of ADT on the FRAX score in prostate cancer patients. METHODS: The assessment of the FRAX score was performed in a total of 1220 prostate cancer patients, including patients who underwent brachytherapy (n = 547), radical prostatectomy (n = 200), external beam radiation therapy (n = 264) and hormonal therapy alone (n = 187) at Yokohama City University Hospital (Yokohama, Japan). We evaluated the effect of ADT on the FRAX score. RESULTS: Using the FRAX model, the median and mean 10-year probability of a major osteoporotic fracture according to the clinical risk factors alone was 7.9 % (8.8 ± 4.3 %), while the 10-year probability of hip fracture risk was 2.7 % (3.5 ± 3.1 %). In the ADT group, the duration of ADT was correlated with both major osteoporotic risk and hip fracture risk (R(2) = 0.141, p < 0.001 and R(2) = 0.166, p < 0.001, respectively). A comparison between the ADT (n = 187) and non-ADT (n = 399) groups demonstrated that the major fracture risk was > 20 % higher and the hip fracture risk was > 3 % higher in the ADT group than in the non-ADT group (ADT: 10 (5.3 %) and 118 (63.1 %), non-ADT 13 (3.3 %) and 189 (47.4 %), p < 0.001 and p < 0.001, respectively). CONCLUSIONS: These results suggested that the longer duration of ADT led to an increased FRAX score, and the FRAX score may be a predictor of bone management treatment, particularly in prostate cancer patients.

DOI： 10.1186/s12894-016-0151-9

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DOI： 10.1007/s00240-015-0823-z

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DOI： 10.1002/pros.23164

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Editorial Board of Acta Urologica Japonica  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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