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IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder that systemically causes tissue fibrosis due to infiltration of IgG4-positive plasma cells. Here, we reported a rare case of ureteral IgG4-RD that formed a nodular lesion and diagnosed by trans-vaginal ultrasound-guided needle biopsy.A 72-year-old woman presented with loss of appetite. The patient underwent Computed Tomography (CT), and she was pointed out the thickening of the left side bladder wall. So we performed a transurethral bladder biopsy under lumber anesthesia, but histopathological findings were almost normal. After that, she developed pyelonephritis repeatedly. We performed CT again. A CT revealed a nodular lesion at the end of her left ureter and hydronephrosis. The tumor was gradually getting larger. So we performed placement the ureteral stent for urinary tract obstruction. Left ureteral urine cytology was classIIIa. We performed transvaginal ultrasound needle biopsy for the nodular lesion of the left ureter. Histopathological findings showed infiltration of lymphocytes and fibrosis and infiltration of IgG4 positive plasma cells: the ratio of IgG4/IgG positive cells0.6, 30IgG4 positive plasma cells/high power field. The serum IgG and IgG4 levels were also elevated 1,943 and 210 mg/dl. We finally diagnosed IgG4-RD of the ureter and started using steroid for her treatment. One month later, the tumor had reduced after steroid treatment. The ureteral stent was removed. Since then, recurrent ureteral obstruction of the left ureter has not occurred.IgG4-RD of the ureter with nodular type is rare, and the imaging findings are similar to malignant tumors. Accurate diagnosis is very important to rule out malignancy. In our case, transvaginal needle biopsy was helpful to reach final diagnosis.

Overactive bladder (OAB) is a syndrome with symptoms such as urinary frequency, urinary urgency and urge incontinence. The aim of this study is to assess the validity and reliability of the Turkish overactive bladder symptom score (OABSS) and to evaluate the results of mirabegron treatment with OABSS. The study was carried out with 117 patients who applied to the urology outpatient clinic between June 2018–January 2019. OABSS Turkish validation was developed from the English version. Demographic data of the patients were recorded. The OABSS, overactive bladder questionnaire (OAB-v8) and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) were filled out by the patients. The patients were asked to fill in these questionnaires after 2 weeks. Patients receiving mirabegon treatment were evaluated with the same questionnaires and bladder diaries after 8 weeks. A total of 117 OAB patients, including 82 OAB-wet and 35-OAB dry, were included in the study. The mean age of the patients was 46.79 ± 14.26 (18–78) years, and the mean duration of OAB complaint was 32.28 ± 32.21 months. The mean score of the OABSS is 9.9 ± 3.14. The results of the reliability assessment showed that the intraclass correlation coefficient of the total OABSS score was 0.71 (weighted coefficients of individual item points, 0.635–0.831), and the Cronbach α was 0.736. In the validity analysis, the OABSS total score was highly correlated with that belonging to other questionnaire forms (OAB-v8, ICIQ-SF and bladder diary). After the treatment with mirabegron, mean OABSS scores of the patients improved significantly from baseline to the 8th week (p

Objectives Perinephric fat invasion (PFI) of renal cell carcinoma (RCC) is known to be associated with adverse pathological features and poor prognosis. We analyzed these associations using a sub-group of the RCC registry of The Cancer Registration Committee of the Japanese Urological Association. Methods The study cohort of 2998 non-metastatic cases was retrieved from RCC registry (3648 in total). We compared clinicopathological characteristics of cases with PFI (n = 256) and without PFI (n = 2742), and investigated the impact of PFI on cancer-specific survival using univariate and multivariate analyses. Results Compared with non-PFI cases, PFI cases were older (P = 0.003), and more likely to be hypertensive (P = 0.034) and symptomatic at presentation (P < 0.001). PFI tumors were larger (P < 0.001), and more often have sarcomatoid component (P < 0.001) and tumor thrombus (P < 0.001). Cancer-specific survival was significantly shorter in cases with PFI than without (P < 0.001). The difference in survival tended to be greater in cases with large tumors but was significant in small tumor sub-groups. Cancer-specific survival was significantly shorter in cases with both PFI and renal vein involvement (RVI) in comparison to those with PFI or RVI alone (P = 0.011, P = 0.007, respectively). On multivariate analysis PFI with and without sinus fat invasion remained as an independent risk factor along with symptom at presentation, low body mass index, hypertension, multiple tumors, large tumor size (>7.0 cm), sarcomatoid component and RVI. Conclusions PFI was associated with advanced age and aggressive pathological features. PFI is an independent prognostic factor in non-metastatic RCC.

Aims To determine whether ultrasound-assisted prompted voiding (USAPV) care is more efficacious than conventional prompted voiding (CPV) care for managing urinary incontinence in nursing homes. Methods Thirteen participating nursing homes in Japan were randomized to CPV (n = 7) or USAPV care group (n = 6). Residents of the allocated nursing homes received CPV (n = 35) or USAPV (n = 45) care for 8 weeks. In the CPV group, caregivers asked the elderly every 2-3 h whether they had a desire to void and prompted them to void when the response was yes. In the USAPV group, caregivers regularly monitored bladder urine volume by an ultrasound device and prompted them to void when the volume reached close to the individually optimized bladder capacity. Frequency-volume chart was recorded at the baseline and after the 8-week intervention to measure the daytime urine loss. Results The change in daytime urine loss was statistically greater in the USAPV (median, -80.0 g) than in the CPV (median, -9.0 g; P = .018) group. The proportion of elderly individuals whose daytime urine loss decreased by >25% was 51% and 26% in the USAPV and CPV group, respectively (P = .020). Quality-of-life measures of elderly participants showed no significant changes in both groups. The care burden scale score of caregivers was unchanged in the USAPV group (P = .59) but significantly worsened in the CPV group (P = .010) after the intervention. Conclusions USAPV is efficacious and feasible for managing urinary incontinence in nursing homes.

Objectives To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron. Methods During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions. Results Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores. Conclusions Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

Aims The efficacy of perioperative pelvic floor muscle training (PFMT) for continence recovery after robot-assisted radical prostatectomy (RARP) remains unclear. Visualization of the bladder neck and urethra using transperineal ultrasound (US) may promote self-recognition of urethral closure during PFM contraction. This study aimed to examine whether transperineal US-guided PFMT promotes early recovery of post-RARP incontinence. Methods This prospective cohort study included 116 men undergoing RARP. All men were offered to undergo transperineal US-guided PFMT, and 36 men agreed. The protocol consisted of biofeedback PFMT using transperineal US before RARP and 1-month after RARP with verbal instruction of PFMT immediately after urethral catheter removal. The remaining 80 patients received verbal instruction for PFMT alone. Continence recovery was defined as the number of days requiring a small pad (20 g) per day by self-report. Results No differences were observed in demographic or peri-operative parameters between the two groups except the longer operative time in the US-guided PFMT group. The mean time until continence recovery was significantly shorter in the US-guided PFMT group (75.6 ± 100.0 days) than in the verbal-PFMT group (121.8 ± 132.0 days, P = 0.037). Continence recovery rates within 30 days were 52.8% (19/36) and 35.4% (28/80) in the US-guided PFMT and verbal-PFMT groups, respectively (P = 0.081). US-guided PFMT was associated with better postoperative continence status (adjusted hazard ratio [95% confidence interval]: 0.550 [0.336-0.900], P = 0.017). Conclusions The results showed that transperineal US-guided PFMT perioperatively was associated with early recovery of urinary continence after RARP.

Electrocautery is a promising treatment option for patients with Hunner type interstitial cystitis (HIC), but frequently requires multiple sessions due to recurrence of the lesions. In the present study, we assessed the relationship between the frequency of electrocautery of Hunner lesions and changes in maximum bladder capacity (MBC) at hydrodistension in a large cohort of 118 HIC patients. Three mixed-effect linear regression analyses were conducted for MBC against (1) the number of sessions; (2) the number of sessions and the time between each session and the first session; and (3) other relevant clinical parameters in addition to the Model (2). The mean number of sessions was 2.8 times. MBC decreased approximately 50 mL for each additional electrocautery session, but this loss was offset by 10 mL for each year the subsequent session was postponed. MBC of

Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification. According to the mutational status of TP53, MDM2, RAS, and FGFR3, UTUC is classified into five subtypes having discrete profiles of gene expression, tumor location/histology, and clinical outcome, which is largely recapitulated in an independent UTUC cohort. Sequencing of urine sediment-derived DNA has a high diagnostic value for UTUC with 82.2% sensitivity and 100% specificity. These results provide a solid basis for better diagnosis and management of UTUC., 上部尿路上皮がんの分子分類と新規分子診断 --尿中遺伝子変異の検出で高精度の診断が可能--. 京都大学プレスリリース. 2021-06-15.

The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC90 of 2–64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 μg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum β-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum β-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports.

Background The role of radical prostatectomy in treating non-metastatic prostate cancer patients with high prostate-specific antigen levels remains unclear. We evaluated the feasibility and oncological outcomes of radical prostatectomy in non-metastatic prostate cancer patients with prostate-specific antigen levels of 50 ng/ml or higher. Methods This retrospective study included 31 patients who were diagnosed as very high-risk prostate cancer (clinical stage of any T, N0-1 M0 and PSA levels ≥50 ng/ml) and underwent radical prostatectomy either as a monotherapy or as a component of multimodal therapy (RP group). Surgery-related complications were investigated. Time to castration-resistant prostate cancer, cancer-specific survival, and overall survival were estimated using the Kaplan-Meier method. A total of 47 patients with very high-risk prostate cancer who were treated with androgen deprivation therapy without local therapy served as a control group (ADT group). Survivals were compared between RP group and ADT group in exploratory analyses. Results The median pretreatment prostate-specific antigen was 87 ng/ml and 100 ng/ml in the RP and ADT groups, respectively (P = 0.67). Surgical complications of Clavien-Dindo Grade 3 were documented in nine patients (29%). Ten-year castration-resistant prostate cancer-free, cancer-specific and overall survivals were 78%, 81% and 77% in RP group, respectively, and they were significantly better than those of ADT group (54%, P = 0.006; 54%, P = 0.006 and 38%, P < 0.001). Exploratory multivariate analysis identified radical prostatectomy as the only significant factor associated with a better cancer-specific survival (hazard ratio: 0.25, P = 0.006). Conclusions Radical prostatectomy is feasible for non-metastatic prostate cancer patients with prostate-specific antigen levels of 50 ng/ml or higher. Radical prostatectomy is a viable option for select patients with non-metastatic, very high-risk prostate cancer.

Aims To develop a comprehensive patient-reported bladder assessment tool (BAT) for assessing overactive bladder (OAB) symptoms, bother, impacts, and satisfaction with treatment. Methods Subjects were consented and eligibility was confirmed by a recruiting physician; subjects were then scheduled for in-person interviews. For concept elicitation and cognitive interviews, 30 and 20 subjects, respectively, were targeted for recruitment from US sites. All interviews were conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and analyzed using a qualitative data analysis software program. A draft BAT was created based on the results of the concept elicitation interviews and further revised based on cognitive interviews as well as feedback from an advisory board of clinical and patient-reported outcome (PRO) experts. Results Nocturia, daytime frequency, and urgency were reported by all subjects (n = 30, 100.0%), and incontinence was reported by most subjects (n = 25, 83.3%). The most frequently reported impacts were waking up to urinate (n = 30, 100.0%), embarrassment/shame (n = 24, 80.0%), stress/anxiety (n = 23, 76.7%), and lack of control (n = 23, 76.7%). Following analysis, item generation, cognitive interviews, and advisory board feedback, the resulting BAT contains four hypothesized domains (symptom frequency, symptom bother, impacts, and satisfaction with treatment) and 17 items with a 7-day recall period. Conclusions The BAT has been developed in multiple stages with input from both OAB patients and clinical experts following the recommended processes included in the FDA PRO Guidance for Industry. Once fully validated, we believe it will offer a superior alternative to use of the bladder diary and other PROs for monitoring OAB patients in clinical trials and clinical practice.

Aims To evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique. Methods Bladder biopsy specimens from 31 patients with Hunner type IC and 38 patients with non-Hunner type IC were analyzed. Bladder biopsy specimens from 37 patients without IC, including 19 non-specific chronic cystitis ("non-IC cystitis") specimens and 18 non-inflamed bladder ("normal bladder") specimens, were used as controls. Mast cell tryptase-, CD3-, CD20-, and CD138-immunoreactive cells were quantified using digital image analysis software to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and lymphoplasmacytic cell densities were counted independently in the entire lamina propria and detrusor areas and compared among the four groups. Results In the lamina propria, there were no significant differences in mast cell and lymphoplasmacytic cell densities between Hunner type IC and non-IC cystitis or between non-Hunner type IC and normal bladder specimens. In the detrusor, the mast cell densities were not significantly different among the four groups. Mast cell density was correlated with lymphoplasmacytic cell density, but not with clinical parameters. Conclusions Mast cell density is not significantly different between IC specimens and non-IC control specimens with a similar degree of background inflammation. The intensity of mast cell infiltration generally correlated with that of lymphoplasmacytic cells. We conclude that mast cell count is of no value in the differential diagnosis between IC and other etiologies.

Inactivating mutation and consequent expression loss of stromal antigen 2 (STAG2, also known as SA2), a component of the cohesion complex, is one of the most common genetic aberrations in urothelial carcinoma. However, the clinicopathologic or prognostic significance of STAG2 alterations in upper tract urothelial carcinoma (UTUC) is largely unknown. This study immunohistochemically examined the expression of STAG2 in 171 patients with UTUC. The correlations of STAG2 loss with clinicopathologic features and patients’ prognoses were examined. Loss of STAG2 expression was observed in 28 cases (16%). Loss of STAG2 was significantly correlated with histological low grade, papillary architecture, noninvasive tumors, absence of concomitant carcinoma in situ, and lower Ki-67 expression. Loss of STAG2 alone was not significantly associated with patients’ prognoses in either the uni- or multivariate analysis. However, STAG2 loss was significantly associated with worse clinical outcome in UTUC with high Ki-67 proliferation indexes, but not in UTUC with low Ki-67 expression. Loss of STAG2 was generally associated with less aggressive features in UTUC. However, the STAG2 loss was an ominous sign in the subpopulation with higher Ki-67 proliferation indexes. Examining both STAG2 and Ki-67 status may be useful for identifying aggressive clinical behavior of UTUC.

Background Analyses of associations between clinicopathologic outcomes and recurrent somatic mutations in clear cell renal cell carcinoma (ccRCC) have been limited to individual cohorts. Objective To define clinicopathologic associations between specific mutations and ccRCC disease characteristics. Design, setting, and participants DNA sequencing data were pooled from three collaborative genomic cohorts ( n =754) and our institutional database ( n =295). All patients had clinical data and identification of somatic mutations from their primary tumors. Outcome measurements and statistical analysis Analysis of gene mutations for associations with maximal tumor size (linear regression) and pathologic stage (logistic regression). Cancer-specific survival (CSS) and recurrence-free survival (RFS) were calculated using competing risks methods. Analyses were adjusted for cohort site, and results were adjusted for multiple testing ( q value). Relevant genes were used in multivariable models that included confounding variables and the validated Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score. Results and limitations Association with tumor size was found for mutations in BAP1 ( q =0.013). No mutations were found to be associated with stage after adjusted analysis. Mutations in BAP1 ( q =0.004) and TP53 ( q =0.001) were associated with decreased CSS in a multivariable model; only TP53 ( q =0.005) remained significant when SSIGN score was included. SETD2 mutations ( q =0.047) were associated with decreased RFS in multivariable models, including models with SSIGN score. Conclusions In >1000 patients with ccRCC, pooled analysis and multivariable modeling demonstrated that three mutated genes have statistically significant associations with poor clinical outcomes. This included the more commonly mutated BAP1 and SETD2 and the less frequently mutated TP53 . After adjustment for clinical confounders, mutations of TP53 and SETD2 were associated with decreased CSS and RFS, respectively. Patient summary Using rigorous statistical methods, this study affirmed that certain mutations in clear cell renal cell carcinoma may portend inferior survival and an increased risk of recurrence.

Aims To examine the outcomes of lower urinary tract symptoms (LUTS) and urodynamic test results after cerebrospinal fluid (CSF) shunt surgery in idiopathic normal pressure hydrocephalus (iNPH). Methods Records of 48 patients (33 men; 15 women), who met the definite iNPH criteria and underwent CSF shunt surgery, were retrospectively analyzed. LUTS and their impact on quality of life (QOL) were evaluated using an all-or-none questionnaire targeting four symptoms, the Overactive Bladder Symptoms Score (OABSS), and the QOL index. Urodynamic investigations included filling cystometry and pressure-flow studies performed before and after surgery. Results Forty-seven (98%) patients complained of LUTS, 41 (87%) patients of whom experienced LUTS improvement after surgery. The OABSS and QOL index, which before surgery were 6.8 ± 0.7 and 4.1 ± 0.4, respectively, significantly decreased to 4.6 ± 0.6 and 3.2 ± 0.3, respectively, after surgery. The maximum cystometric capacity (174.9 ± 13.3 mL to 222.4 ± 14.7 mL) and bladder compliance (35.8 ± 4.4 ml/cmH2O to 52.1 ± 5.4 ml/cmH2O) significantly increased after surgery. Detrusor overactivity, which was observed in 37 (77%) patients preoperatively, became undetectable in 7 patients postoperatively. Voiding dysfunction (defined as maximum flow rate 100 mL) was observed in 29 (60%) patients, 22 (75%) of whom had detrusor underactivity before surgery. None of the voiding urodynamic parameters significantly improved postoperatively. Conclusions iNPH is often associated with LUTS and both storage and voiding dysfunctions. CSF shunt surgery improved LUTS and storage dysfunction, with limited effects on voiding dysfunction.

The present article is the abbreviated English translation of the Japanese guidelines for male lower urinary tract symptoms and benign prostatic hyperplasia updated as of the end of 2016. The target patients are men aged >50 years complaining of lower urinary tract symptoms, with or without benign prostatic hyperplasia, and the target readers are non-urological general physicians and urologists. Mandatory assessment for general physicians is medical history, physical examination, urinalysis and measurement of serum prostate-specific antigen. Additional mandatory assessment for urologists is symptoms and quality of life assessment by questionnaires, uroflowmetry, residual urine measurement, and prostate ultrasonography. Nocturia requires special attention, as it can result from nocturnal polyuria and/or sleep disturbance rather than lower urinary tract disorders. Functional lower urinary tract disorders with or without benign prostatic hyperplasia are primarily managed by conservative therapy and medications, such as α1 -blockers and phosphodiesterase-type 5 inhibitors. Use of other medications or combination pharmacotherapy is to be reserved for urologists. 5α-Reductase inhibitors and anticholinergics or β3 agonists are indicated for men with enlarged prostates and overactive bladder symptoms, respectively. Surgical intervention for bladder outlet obstruction is considered for persistent symptoms or benign prostatic hyperplasia-related comorbidities. Surgical modalities should be optimized by the patient's characteristics, performance of equipment and the surgeon's experience.

Objectives To investigate predictors of continence outcomes after robot-assisted radical prostatectomy. Methods Clinical records of 272 patients who underwent robot-assisted radical prostatectomy were investigated. Preoperative Overactive Bladder Symptom Score, International Prostate Symptom Score and clinicopathological factors were investigated, and relationships between factors and recovery of continence after robot-assisted radical prostatectomy were assessed. The presence of overactive bladder was defined as having urgency for more than once a week and having ≥3 points according to the Overactive Bladder Symptom Score. Results Age (≤66 years) was significantly associated with continence within 6 months after robot-assisted radical prostatectomy (P = 0.033). The absence of overactive bladder and lower Overactive Bladder Symptom Score (

To evaluate the efficacy of adjuvant systemic chemotherapy for locally advanced (pT3-4pN0/xM0) upper tract urothelial carcinoma (UTUC). We retrospectively reviewed the medical records of 109 patients with pT3-4pN0/xM0 UTUC who had undergone radical nephroureterectomy between 1996 and 2013 at our four institutions. The patients were divided into two groups: those who received adjuvant chemotherapy (AC group) and those who did not (surgery-alone: SA group). All chemotherapy regimens were cisplatin-based. Cox proportional hazards regression models addressed the associations between clinicopathological factors and recurrence-free survival (RFS) and cancer-specific survival (CSS). Forty-three (39.5%) out of the 109 patients underwent one to four cycles of adjuvant chemotherapy after nephroureterectomy. Median follow-up was 46.5 months. There were no significant differences in the background characteristics of the two groups, except for age. Recurrence developed in 11 (25.6%) and 29 (43.9%) patients in the AC and SA groups, respectively. Ultimately, six (14.0%) and 18 (27.3%) patients in the AC and SA groups, respectively, died of disease progression. On univariate analysis, hydronephrosis, nuclear grade, lymphovascular invasion, and adjuvant chemotherapy were significantly associated with both RFS and CSS. Charlson comorbidity index was associated only with CSS. On multivariate analysis, adjuvant chemotherapy was the only independent factor associated with improved RFS (p = 0.0178, HR = 0.41). Moreover, adjuvant chemotherapy (p = 0.0375, HR = 0.33), lower nuclear grade (p = 0.0070), and the absence of hydronephrosis (p = 0.0493) were independently associated with better CSS. Locally advanced (pT3-4pN0/xM0) UTUC patients who underwent cisplatin-based adjuvant chemotherapy demonstrated better RFS and CSS than those without adjuvant chemotherapy.

// Xue Gong 1,2 , Zurab Siprashvili 3 , Okyaz Eminaga 1,4 , Zhewei Shen 2 , Yusuke Sato 5,6 , Haruki Kume 6 , Yukio Homma 6 , Seishi Ogawa 5 , Paul A. Khavari 3 , Jonathan R. Pollack 2 and James D. Brooks 1 1 Department of Urology, School of Medicine, Stanford University, Stanford, California, USA 2 Department of Pathology, School of Medicine, Stanford University, Stanford, California, USA 3 Program in Epithelial Biology, School of Medicine, Stanford University, Stanford, California, USA 4 Department of Urology, University Hospital Cologne, Cologne, Germany 5 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 6 Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Correspondence to: Jonathan R. Pollack, email: // James D. Brooks, email: // Keywords : lincRNA, renal cell carcinoma, kidney cancer, biomarker, prognostication Received : November 04, 2016 Accepted : January 24, 2017 Published : February 24, 2017 Abstract Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior, and prognostic biomarkers are needed to stratify patients for appropriate management. We sought to determine whether long intergenic non-coding RNAs (lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data on 466 ccRCC cases (randomized into discovery and validation sets) annotated for ~21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival-predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and validated in an independent University of Tokyo cohort ( P =0.004). In multivariable analysis, SLINKY expression predicted overall survival independent of tumor stage and grade [TCGA HR=3.5 (CI, 2.2-5.7), P < 0.001; Tokyo HR=8.4 (CI, 1.8-40.2), P = 0.007], and by decision tree, ROC and decision curve analysis, added independent prognostic value. In ccRCC cell lines, SLINKY knockdown reduced cancer cell proliferation (with cell-cycle G 1 arrest) and induced transcriptome changes enriched for cell proliferation and survival processes. Notably, the genes affected by SLINKY knockdown in cell lines were themselves prognostic and correlated with SLINKY expression in the ccRCC patient samples. From a screen for binding partners, we identified direct binding of SLINKY to Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK), whose knockdown recapitulated SLINKY knockdown phenotypes. Thus, SLINKY is a robust prognostic biomarker in ccRCC, where it functions possibly together with HNRNPK in cancer cell proliferation.

The aim of the present study was to elucidate the details of bone metastasis (BM) and the resulting skeletal-related events (SREs), and survival and prognostic factors, in urothelial cancer (UC) patients with BM. A total of 48 UC patients with BM who were treated at our institution between 1994 and 2013 were enrolled. Details of BM and SREs were investigated. The Kaplan–Meier method was used to estimate survival duration. Relationships between several clinical features and survival were analyzed using the log-rank test and the Cox hazard model. Of the 48 patients, 39 (81.3%) were male, with a median age at diagnosis of BM of 68 years [interquartile range (IQR), 61–75 years]. Frequent metastatic sites included the pelvis (31 patients, 64.6%) and spine (28, 58.3%). SREs occurred in 31 patients (64.6%) at a median duration of 0.9 months (IQR, 0.3–5.4 months) after diagnosis of BM, including radiation therapy (n = 23; 74.2%), spinal cord compression (n = 4; 12.9%), pathological fracture (n = 3; 9.7%) and hypercalcemia (n = 1; 3.2%). Median overall survival periods after diagnosis of BM and SREs were 6.2 and 5.6 months, respectively. On multivariate analysis, factors significantly associated with survival after BM were performance status [hazard ratio (HR) for ≥2 vs. 0–1, 4.94; P = 0.0003], liver metastasis (HR, 4.08; P = 0.0018), chemotherapy after BM (HR, 0.31; P = 0.0018), and use of bone-modifying agents (HR, 0.36; P = 0.0147). We revealed clinicopathological factors that are predictive of prognosis of UC patients with BM. Although the prognosis is poor, chemotherapy and bone-modifying agents may confer survival benefits.

Objective Suplatast tosilate, a Th2 cytokine inhibitor, was predicted to relieve interstitial cystitis symptoms. Four studies with suplatast tosilate in Japanese interstitial cystitis patients have been conducted: a single-arm clinical study, a phase II dose-ranging trial, a phase III trial with placebo, and a second phase PIII trial with placebo. Treatment efficacy was observed in the first two studies; however, in the phase PIII trials, no significant difference in interstitial cystitis symptom score changes was observed between suplatast tosilate and placebo. We summarized these four studies to investigate factors causing the difference in observed efficacy. Methods Placebo effects in the first two studies and differences regarding study design between the four studies were considered to be possible factors. Therefore, placebo effects were investigated by comparing interstitial cystitis symptom score changes, and the study designs were compared to investigate the effects on observed efficacy. Results Interstitial cystitis symptom score changes in the phase PII treatment groups increased in a dose-dependent manner and showed an almost linear relationship with interstitial cystitis symptom score changes observed in placebo groups of 2 phase PIII studies. A major difference regarding the phase PIII study design was the use of diagnostic hydrodistention. Diagnostic hydrodistention and its washout period were applied only in the phase PIII trials. Conclusions Comparison of interstitial cystitis symptom score changes suggested that the placebo effect was very small. Use of diagnostic hydrodistention was considered to be a major difference in the population characteristics of the studies and may have resulted in different observed efficacies. Diagnostic hydrodistention, which potentially influences the treatment effect, is probably not essential for trials of suplatast in interstitial cystitis patients.

We systematically characterized gene expression, inflammation and neovascularization in patients with interstitial cystitis/bladder pain syndrome to obtain biological evidence supporting diagnosis and classification.We sequenced RNA obtained from bladder mucosal biopsies of 33 patients with 3 subtypes of interstitial cystitis/bladder pain syndrome, including Hunner lesions in 12, no Hunner lesions in 11 but with glomerulations and neither Hunner lesions nor glomerulations in 10, and 9 controls. Differentially expressed genes of each subtype were searched to identify subtype specific biological pathways and candidate genes important for pathogenesis. Candidate genes were validated by quantitative polymerase chain reaction and immunohistochemistry. Digital immunohistochemical quantification was performed to assess subepithelial lymphoplasmacytic cell and microvessel density. Relationships between candidate gene over expression and symptom severity were explored.Patients with Hunner lesions showed a distinct gene expression profile associated with significant up-regulation of biological processes involving immune responses and infection, and an increase in subepithelial lymphoplasmacytic cell and microvessel density. Over expression of 2 candidate genes, VEGF and BAFF, correlated with symptom severity. Meanwhile, the gene expression profiles of patients with the 2 subtypes without Hunner lesions were similar to those of controls. No difference in biological pathways or subepithelial lymphoplasmacytic cell and microvessel density were detected between these 2 subtypes and controls.Interstitial cystitis/bladder pain syndrome with Hunner lesions shows distinct genomic and histological features associated with immune responses and infection. In addition, VEGF and BAFF are potential disease biomarkers and therapeutic targets. This subtype should be considered separate from the syndrome.

AIMS To clarify longitudinal change of lower urinary tract symptoms (LUTS) and various types of urinary incontinence following robot-assisted radical prostatectomy (RARP) using validated questionnaires. MATERIALS AND METHODS The core lower urinary tract symptom score (CLSS) and the International Consultation on Incontinence Questionnaire (ICIQ)-Short Form (SF) questionnaires were administered to 607 consecutive, treatment-naive men receiving RARP before and after surgery. The time course of comprehensive LUTS and various types of urinary incontinence, including stress-, urgency-, and urinary incontinence with no obvious reason, were evaluated. Continence recovery rates were compared for the different types of incontinence using Cox hazard regression analysis. RESULTS After surgery, stress urinary incontinence (SUI) was reported most frequently (32% of cases) as the chief complaint with the most impact on daily life, as assessed by the CLSS questionnaire, followed by urgency urinary incontinence (UUI; 27% of cases). The rates of continence recovery differed among the different types of urinary incontinence, such as after urinating, when dressed, when asleep, when physically active or exercising, when coughing or sneezing, before reaching the toilet, and for no obvious reason. Incontinence for no obvious reason at 1 month after RARP was a strongest prognostic factor of delayed continence recovery (hazard ratio, 0.61; P

Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. Nineteen (61.3 %) died of SCCB during the follow-up, with a median survival time of 12.7 months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE ≥25 ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p = 0.0022). Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB.

Background The androgen receptor (AR) plays a key role in the development of prostate cancer. AR signalling mediates the expression of androgen-responsive genes, which are involved in prostate cancer development and progression. Our previous chromatin immunoprecipitation study showed that the region of abhydrolase domain containing 2 (ABHD2) includes a functional androgen receptor binding site. In this study, we demonstrated that ABHD2 is a novel androgen-responsive gene that is overexpressed in human prostate cancer tissues. Methods The expression levels of ABHD2 in androgen-sensitive cells were evaluated by quantitative reverse transcription polymerase chain reaction and western-blot analyses. LNCaP and VCaP cells with ABHD2 overexpression or short interfering RNA (siRNA) knockdown were used for functional analyses. ABHD2 expression was examined in clinical samples of prostate cancer by immunohistochemistry. Results We showed that ABHD2 expression is increased by androgen in LNCaP and VCaP cells. This androgen-induced ABHD2 expression was diminished by bicalutamide. While stable expression of ABHD2 affected the enhancement of LNCaP cell proliferation and migration, siRNA-mediated ABHD2 knockdown suppressed cell proliferation and migration. In addition, the siRNA treatment significantly repressed the tumour growth derived from LNCaP cells in athymic mice. Immunohistochemical analysis of ABHD2 expression in tumour specimens showed a positive correlation of ABHD2 immunoreactivity with high Gleason score and pathological N stage. Moreover, patients with high immunoreactivity of ABHD2 showed low cancer-specific survival rates and a resistance to docetaxel-based chemotherapy. Conclusion ABHD2 is a novel androgen-regulated gene that can promote prostate cancer growth and resistance to chemotherapy, and is a novel target for diagnosis and treatment of prostate cancer.

Bladder cancer is common in Western countries, but not in Japan. Established risk factors are smoking and high-risk jobs such as printing and manufacturing. The risk of alcohol consumption in bladder cancer has been the recent focus; however, available literature on alcohol consumption and bladder cancer has been limited from Japanese population, thought to have a weak genetic tolerance to acetaldehyde. We aimed to determine whether alcohol consumption is an independent risk factor for bladder cancer among Japanese. The study was a matched case-control study from the nationwide Japanese clinical database administered by the Rosai Hospital group. We identified 739 cases of bladder cancer diagnosed between 2005 (when the database was established) and 2014 and 7,196 controls matched by sex, age, hospital, and admission period. We estimated the odds ratio of alcohol consumption for bladder cancer adjusted for the amount of smoking, high-risk occupations, and comorbidities (hypertension, hyperlipidemia, diabetes, hyperuricemia, and obesity) with conditional logistic regression. The risk of bladder cancer was significantly higher in ever drinkers than in never drinkers (odds ratio, 1.33; 95% confidence interval, 1.06 to 1.66). Furthermore, the risk threshold for alcohol consumption was more than 15 g of alcohol intake per day (one, 180-mL cup equivalent to 6 ounces of Japanese sake containing 23 grams of alcohol). Among Japanese, alcohol consumption may be an independent risk factor for bladder cancer, with a lower risk threshold.

The number of patients diagnosed with renal tumor has been increasing with the extensive application of ultrasonography and computed tomography (CT).1 Surgical resection remains necessary for a definitive diagnosis of renal tumor, but it is not always clinically beneficial, especially for elderly patients or those with severe comorbidities. For these patients, avoiding surgery and proceeding to active surveillance has become the mainstay of patient management.2,3 Without surgical intervention, the evaluation of tumor malignancy is helpful for treatment strategy decisions such as the timing of surgery or maintaining active surveillance. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a widely used effective modality for evaluating tumor activity by estimating glucose metabolism. The usefulness of FDG-PET imaging in oncology is based on a correlation between glucose metabolism and the degree of tumor malignancy, which has been reported for various tumors.4–12 Although we have observed differential FDG uptake in renal tumor, there are few studies concerning FDG-PET for renal cell carcinoma (RCC), most likely because of difficulties in differentiating the radioactivity of FDG accumulated in renal tumors from the radioactivity of FDG excreted via the urinary system during physiological processes. In addition, false-negative cases can lead to a low sensitivity for RCC detection.13–15 The use of FDG-PET for routine evaluation of renal tumors has not been recommended. However, recently dedicated PET-CT have improved image resolution and signal-to-noise ratio. In addition, attached-CT for photon attenuation correction provides anatomical information on FDG-PET images. A comparison of diagnostic CT and attached-CT facilitates the identification of renal tumors on FDG-PET images, which enable us to place region of interest (ROI) on renal tumor more accurately. Calculation semiquantitative values using these ROI help elucidate the characteristics of FDG uptake of a renal tumor. In this study, we hypothesized that glycolytic metabolism would reflect tumor aggressiveness in renal tumors. Pathological findings such as histological subtype, nuclear grade, and TNM stage are the most widely used indicators for renal tumor aggressiveness.16–18 We investigated the correlation of preoperative renal tumor metabolic activity with tumor pathology. This study applied a semiquantitative value of metabolism as defined by the standardized uptake value (SUV) in a greater number of cases than previously investigated.

BACKGROUND/AIM The aim of this study was to demonstrate the clinical significance of latent Gleason pattern (GP) 5 occasionally found in prostatectomy specimens. MATERIALS AND METHODS Patients (n=605) undergoing radical prostatectomy were classified into three groups according to the presence of GP5 in the biopsy or in the prostatectomy specimens: 'GP5 negative', absence of GP in both specimens 'latent GP5', absence of GP5 in the biopsy specimen, but presense of GP5 in the prostatectomy specimen, and 'GP5 positive', presense of GP in both specimens. The characteristics of these three groups were analyzed. RESULTS There were 381 men in the GP5-negative group, 155 in the latent GP5 group, and 69 in the GP5-positive group. Low- or intermediate-risk for prostate cancer, latent GP5 and surgical margin positivity were independent predictors of biochemical recurrence (Hazard ratio (HR): 3.1, 5.8, respectively, p=0.001, 0.0002, respectively). CONCLUSION Latent GP5 is an important prognostic factor that should be evaluated in patients with low- and intermediate-risk for prostate cancer before the initiation of treatment.

OBJECTIVE This study examined the accuracy of a new portable ultrasound bladder scanner, the Lilium α-200 (Lilium Otsuka, Kanagawa, Japan), by evaluating the correlation between bladder volumes periodically measured by the Lilium α-200 and instilled volume during video-urodynamic studies (V-UDS). METHODS Using the Lilium α-200, fluid volume was measured prospectively in the bladders of patients with lower urinary tract dysfunction during V-UDS. This was done both immediately after micturition (for assessment of post-void residual [PVR] volume) and at 1-minute intervals during filling cystometry with patients in the supine position. These measurements were then compared with the PVR volume obtained directly by catheter drainage and instilled volume during cystometry using paired t tests and Spearman's rank correlation. RESULTS Fifteen male patients (median age 70.5 years; range 18-84 years) were included in the study. The PVR volume measured by the Lilium α-200 was strongly correlated with that obtained by catheter drainage (r = 0.94; P < 0.0001). There was a strong correlation between instilled and bladder volumes measured by the Lilium α-200 at every minute during and at the end of instillation (281 measurements in 15 patients; r = 0.86; P < 0.0001). However, the relative error of bladder volumes measured by the Lilium α-200 during cystometry showed considerable variation (mean [± SD] 5.6 ± 62.9%). CONCLUSIONS Bladder volumes measured periodically by the Lilium α-200 during cystometry were strongly correlated with actual PVR or instilled volumes. However, they showed considerable variation and may not predict actual volume accurately. The Lilium α-200 is feasible for obtaining an approximate measure of bladder volume.

Background This study compared the detection rates for clinically significant prostate cancer (CSPC) between magnetic resonance imaging and ultrasonography (MRI/US)-fusion-targeted biopsy (TB), systematic biopsy (SB) and combination of TB and SB. Methods This prospective study evaluated simultaneous TB and SB for consecutive patients with suspicious lesions that were detected using pre-biopsy multiparametric MRI. A commercially available real-time virtual sonography system was used to perform the MRI/US-fusion TB with the transperineal technique. The prostate imaging reporting and data system version 2 (PI-RADS v2) was assigned to categorize the suspicious lesions. Results A total of 177 patients were included in this study. The detection rate for CSPC was higher using SB, compared to TB (57.1% vs 48.0%, p = 0.0886). The detection rate for CSPC was higher using the combination of TB and SB, compared to only SB (63.3% vs 57.1%, p = 0.2324). Multivariate analysis revealed that PIRADS v2 category 4 and an age of

OBJECTIVE To compare nationwide outcomes of tension-free vaginal mesh surgery and laparoscopic sacrocolpopexy for the treatment of pelvic organ prolapse in Japan. METHODS Using the Diagnosis Procedure Combination database, we collected data on female patients who underwent tension-free vaginal mesh surgery or laparoscopic sacrocolpopexy for pelvic organ prolapse from April 2014 to March 2015. We compared the proportion of perioperative adverse events, duration of anesthesia, total costs and postoperative length of stay between the groups. Univariate and multivariate analyses were carried out for age, comorbidity, mesh volume, additional concomitant surgery and hospital volume. RESULTS We identified 3023 patients, including 2388 who underwent tension-free vaginal mesh surgery, and 635 who underwent laparoscopic sacrocolpopexy. The median age at the time of surgery was significantly higher in the tension-free vaginal mesh group (71 vs 66 years; P < 0.001). The tension-free vaginal mesh group had a higher proportion of all adverse events (7.1% vs 1.8%; P < 0.001) and a higher proportion of genitourinary complications (5.7% vs 1.1%; P < 0.001). The median duration of anesthesia was shorter in the tension-free vaginal mesh group (150 vs 286 min; P < 0.001). The total cost was significantly lower in the tension-free vaginal mesh group. CONCLUSIONS Both procedures offer favorable results for surgical treatment of pelvic organ prolapse. Overall, the tension-free vaginal mesh procedure seems to represent a good option for high-risk women, such as elderly patients, whereas laparoscopic sacrocolpopexy is useful for younger patients with a higher level of sexual activity.

Objectives To describe the clinicopathological features and oncological outcomes of renal cell carcinoma diagnosed in Japan in 2007, the results of the large-scale renal cell carcinoma registration study carried out by the Japanese Urological Association are reported. Methods The renal cell carcinoma survey was carried out by the Japanese Urological Association in 2012 to register newly diagnosed renal cell carcinoma cases in 2007 from 340 institutions nationwide. The survey included clinicopathological details, such as sex, age, family history, past history, smoking history, body mass index, reason for diagnosis, TNM classification, stage, histopathology, treatment and clinical outcomes. Results A total of 3663 cases diagnosed in 2007 were registered in this renal cell carcinoma registry program from 340 institutions. A total of 15 patients with a final diagnosis of oncocytoma were excluded, and 3648 cases of renal cell carcinoma were analyzed to evaluate oncological outcomes. The patients’ median age was 63.9 years (range 5.9–95.1 years). Clear cell renal cell carcinoma was the most common histological subtype (77.2%), followed by papillary (5.0%) and chromophobe (3.2%) renal cell carcinoma. The most common initial treatment was radical nephrectomy (72.6%), and the most common secondary treatment was cytokine therapy (13.1%). Five-year overall survival rates in stages I, II, III, and IV were 94.8%, 90.2%, 78.8% and 39.6%, respectively. The 5-year overall survival rates for clear cell, papillary and chromophobe renal cell carcinomas, and carcinoma of the collecting ducts of Bellini were 88.6%, 79.8%, 93.0% and 40.0%, respectively. Conclusions The present report is the first nationwide large-scale study to describe the clinicopathological characteristics and oncological outcomes of patients with renal cell carcinoma in Japan. Oncological outcomes depend on the clinical stage and histological subtype. Further investigations will be required to show improved oncological outcomes in the molecular targeted therapy era using the results of the present study as a baseline.

Objectives To determine whether botulinum toxin type A can represent an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies. Methods This is a single-center, prospective, open labeled, randomized comparative study. Patients with refractory interstitial cystitis were randomly divided into two groups: immediate injection (group A) or 1-month delayed injection (group B) of botulinum toxin type A after allocation. The rate of treatment response (global response assessment ≥+1: slightly improved), and changes in symptom scores and frequency volume chart variables were compared between groups 1 month after allocation. Using subjects of both groups as a single cohort, predictive factors for treatment response at 1 month post-injection and the duration of response were explored. Results A total of 34 patients (group A n = 18, group B n = 16) were allocated. The response rate was significantly higher in group A than group B (72.2% vs 25.0%, P = 0.01). All symptom measures showed significant improvement in group A than group B. When both groups were combined as a single cohort, the response rate was 73.5% at 1 month, 58.8% at 3 months, 38.2% at 6 months and 20.6% at 12 months. The mean duration of response was 5.4 months. Multivariate analysis showed that past exposure to hydrodistension more than three times correlated with better outcomes. Conclusions Botulinum toxin type A injection could be an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies, especially for those who have received repeated hydrodistensions and transurethral fulguration.

Integrated sequencing analysis identified a group of tumors among clear cell renal cell carcinomas characterized by hotspot mutations in TCEB1 (a gene that contributes to the VHL complex to ubiquitinate hypoxia-inducible factor). We analyzed 11 tumors from two distinct cohorts with TCEB1 mutations along with an expanded cohort to assess whether these should be considered an entity distinct from clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma. All tumors were characterized by hotspot mutations in TCEB1 Y79C/S/F/N or A100P. Morphological and immunohistochemical characteristics of the tumors were assessed by two experienced genitourinary pathologists. Clinical and pathological variables, copy number alterations, mutations, and expression signatures were compared with a cohort of TCEB1 wild-type tumors. All TCEB1-mutated tumors were VHL and PBRM1 wild type and contained distinct copy number profiles including loss of heterozygosity of chromosome 8, the location of TCEB1 (8q21.11). All tumors lacked the clear cell renal cell carcinoma signature 3p loss and contained distinct gene expression signatures. None of the clear cell papillary tumors harbored TCEB1 mutations. Pathologically, all TCEB1-mutated tumors shared characteristic features including thick fibromuscular bands transecting the tumor, pure clear cell cytology frequently with cells showing voluminous cytoplasm, and clear cell renal cell carcinoma-like acinar areas associated with infolding tubular and focally papillary architecture. The presence of voluminous cytoplasm, absence of luminal polarization of tumor nuclei, and lack of extensive cup-like distribution of carbonic anhydrase-IX expression distinguish it from clear cell papillary carcinoma. None of the patients developed metastases at last follow-up (median 48 months). In sum, TCEB1-mutated renal cell carcinoma is a distinct entity with recurrent hotspot mutations, specific copy number alterations, pathway activation, and characteristic morphological features. Further clinical follow-up is needed to determine whether these tumors are more indolent compared with the conventional clear cell renal cell carcinoma.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis, which is known to affect various organs; however, there have been no reports of its intrapelvic involvement. We herein describe the case of 69-year-old man who died of a rapidly-growing intrapelvic tumor, which was finally diagnosed as ECD at autopsy. Immunohistochemically, the tumor cells were positive for CD68 and BRAF V600E, and negative for CD1a. Since BRAF V600E has recently been reported to be specific to ECD, it can be a useful biomarker for diagnosis, especially in atypical cases.

Androgen receptor (AR) signaling is essential for the development of prostate cancer. Here, we report that runt-related transcription factor (RUNX1) could be a key molecule for the androgen-dependence of prostate cancer. We found RUNX1 is a target of AR and regulated positively by androgen. Our RUNX1 ChIP-seq analysis indicated that RUNX1 is recruited to AR binding sites by interacting with AR. In androgen-dependent cancer, loss of RUNX1 impairs AR-dependent transcription and cell growth. The RUNX1 promoter is bound by enhancer of zeste homolog 2 (EZH2) and is negatively regulated by histone H3 lysine 27 (K27) trimethylation. Repression of RUNX1 is important for the growth promotion ability of EZH2 in AR-independent cells. In clinical prostate cancer samples, the RUNX1 expression level is negatively associated with EZH2 and that RUNX1 loss correlated with poor prognosis. These results indicated the significance of RUNX1 for androgen-dependency and that loss of RUNX1 could be a key step for the progression of prostate cancer.

Objective The aim of this study was to evaluate the efficacy and toxicity of the combination of docetaxel, ifosfamide and cisplatin as salvage chemotherapy after failure of standard cisplatin-based regimens for metastatic urothelial carcinoma. Methods We prospectively administered docetaxel, ifosfamide and cisplatin chemotherapy to patients with metastatic urothelial carcinoma refractory to standard cisplatin-based regimens from 2003 to 2013. Patients who had received only adjuvant and/or neoadjuvant chemotherapy were excluded. Eligible patients received every 28 days docetaxel 60 mg/m(2) on Day 1, ifosfamide 1.0 g/m(2) on Days 2-6 and cisplatin 20 mg/m(2) on Days 2-6. The primary endpoints were progression-free survival and overall survival, calculated from the start of docetaxel, ifosfamide and cisplatin chemotherapy. Secondary endpoints included objective response and related toxicity. Results Twenty-six cases received a median of 3.0 cycles of docetaxel, ifosfamide and cisplatin chemotherapy (interquartile range: 2-5), resulting in a median progression-free survival of 3 months (interquartile range: 2-9.5 months) and median overall survival of 8.5 months (interquartile range: 6.5-18.75 months), respectively. Of 26 patients, seven (27%) achieved major treatment responses, with one complete response (4%) and six partial responses (23%). Most of Grade 3/4 toxicities were hematologic events, including leukopenia (77%), anemia (54%) and thrombocytopenia (46%). No death from toxicity was observed. Conclusions Our results indicate that docetaxel, ifosfamide and cisplatin chemotherapy is a tolerable and moderately active regimen for metastatic urothelial carcinoma after failure of standard cisplatin-based regimens.

The pituitary production of human chorionic gonadotropin (hCG) can cause false-positive results during or after germ cell tumor (GCT) treatment. Because hypogonadism leads to pituitary hCG production, testosterone administration test (TAT) has been recommended for pituitary hCG diagnosis. However, little is known about its efficacy for the discrimination of pituitary hCG as detected by currently used hCG assays in treatment of GCT. We conducted a retrospective multicenter study to determine the usefulness of TAT. The study included 60 patients who underwent TAT for the discrimination of pituitary hCG. In principle, serum hCG levels were measured 1 week after testosterone enanthate administration (250 mg). When the serum hCG levels decreased below the normal upper range, the results of TAT were determined positive. In this case, the elevated hCG was considered to be derived from pituitary and not from GCT. Serum hCG levels were normalized after TAT in 36 of 60 patients (60%). Before TAT, the hCG levels were below 1.0 IU/L in 13 patients (36%), 1.0–1.9 IU/L in 11 (31%), 2.0–2.9 IU/L in 7 (19%), and >3.0 IU/L in 5 (14%) of TAT-positive patients. Of them, 28 (78%) patients were successfully managed without further treatment with chemotherapy after TAT. Pituitary hCG was associated with higher levels of LH and not necessarily associated with low levels of testosterone. Determining the TAT status of patients was effective in discriminating pituitary hCG production.

AIMS To assess the clinical impact of Hunner lesions in patients with Hunner type interstitial cystitis (HIC). METHODS The clinical records of 94 HIC patients who underwent their first hydrodistension (with lesion fulguration) were retrospectively reviewed. At surgery, the extent of each lesion was classified in terms of the relative involvement for the whole-bladder luminal surface; we defined four grades of involvement

We hypothesized that presence of plasma cell neoplasms might be a risk for thrombosis of arteriovenous fistulas (AVFs) as well as other well-known factors including age, sex, race, and presence of diabetes mellitus or certain vascular disorders.In this single-center, retrospective study based on medical record data, we investigated the influence of plasma cell neoplasms and the above-mentioned factors on the occurrence of complete occlusive thrombosis of the AVF within 30 days after surgery for creation of the AVF. Thrombosis was defined as the absence of bruit or thrill on auscultation and palpation, throughout systole and diastole.We retrospectively assessed the medical records of 91 patients with end-stage renal failure, including 8 patients with plasma cell neoplasm (5 with multiple myeloma and 3 with amyloid light-chain amyloidosis), who underwent surgical creation of an AVF at the wrist or anatomical snuff box for the first time between April 2014 and December 2016. Early thrombosis (i.e., within 30 days of surgery) occurred in 50.0% (4/8) and 10.8% (9/83) of patients with and without plasma cell neoplasm, respectively (P = 0.013). Multivariate analysis revealed that, after adjusting for baseline characteristics, plasma cell neoplasm was the only significant risk factor for early AVF thrombosis (odds ratio, 38.8; 95% confidence interval, 4.0-378.9; P = 0.0017).Considering the poor prognosis of plasma cell neoplasm and its association with higher risk for AVF thrombosis, another type of vascular access is likely to be more suitable than AVF in such patients.

Background The pathological and oncological outcomes of retro-pubic radical prostatectomy (RRP) and robot-assisted radical prostatectomy (RARP) have not been sufficiently investigated. Methods Treatment-naïve patients with localized prostate cancer (PC) (n = 908; RRP, n = 490; and RARP, n = 418) were enrolled in the study. The clinicopathological outcomes, rate and localization of the positive surgical margin (PSM), localization of PSM, and biochemical recurrence (BCR)-free survival groups were compared between RRP and RARP. Results The median patient age and serum PSA level (ng/mL) at diagnosis were 67 years and 7.9 ng/ml, respectively, for RRP, and 67 years and 7.6 ng/ml, respectively, for RARP. The overall PSM rate with RARP was 21%, which was 11% for pT2a, 12% for pT2b, 9.8% for pT2c, 43% for pT3a, 55% for pT3b, and 0% for pT4. The overall PSM rate with RRP was 44%, which was 12% for pT2a, 18% for pT2b, 43% for pT2c, 78% for pT3a, 50% for pT3b, and 40% for pT4. The PSM rate was significantly lower for RARP in men with pT2c and pT3a (p

Aim To investigate the feasibility of chemokines and cytokines potentially elevated in the bladder tissue of Hunner type interstitial cystitis (HIC) as urinary markers for distinguishing HIC from non-Hunner type interstitial cystitis (NHIC) Methods Urine specimens were collected from 41 HIC patients, 25 NHIC patients, and 31 healthy volunteers (control). The supernatants of urine specimens were subjected to ELISA kits for measurements of 10 cytokines and chemokines, whose gene expression was known to be elevated in HIC bladder tissue. Urinary levels normalized by urinary creatinine (Cr) concentration were compared among three groups. Efficiency in differentiating IC and IC subtypes was explored by ROC analysis. The correlation of marker levels with symptom severity, assessed by O'Leary-Sant's symptom index (OSSI) and problem index (OSPI), was examined. Results The urinary levels of CXCL10 and NGF were significantly higher in HIC than NHIC. CXCL10 and NGF differentiated HIC against NHIC with AUC of 0.78 and 0.68, respectively. Combination of CXCL10 and NGF levels yielded an AUS of 0.81. The CXCL10 cut-off of 53.2 pg/mg Cr had sensitivity of 46.1%, specificity of 93.7%, positive predictive value of 97.7%, and negative predictive value of 60.0%. The urinary level of other cytokines showed no significant difference between HIC and NHIC. Significant correlation with symptoms was detected for CXCL10 alone. Conclusion The results suggested that increased urinary level of CXCL10 combined with or without high NGF level could be a promising supplementary biomarker for differentiating HIC from NHIC with modest sensitivity and high specificity.

Background Evidence regarding volume-outcome effects on peritoneal dialysis (PD) catheter implantation is limited. This study aimed to investigate associations between hospital volume (annual caseload of catheter implantation) and perioperative outcomes. Methods Clinical data for patients who underwent PD catheter implantation from 2007 to 2012 were extracted from the Japanese nationwide Diagnosis Procedure Combination database. Hospital volume was divided into tertiles: low-volume (1 – 6 cases/year), medium-volume (7 – 13 cases/year), and high-volume (≥ 14 cases/year). Multivariate logistic regression analysis for the occurrence of any adverse events and blood transfusion, and gamma-distributed log-linked linear regression analysis for postoperative length of stay were conducted with explanatory variables of hospital volume, age, sex, Charlson comorbidity index, history of hemodialysis, type of anesthesia, and type of hospital. Results Among 906, 855, and 744 cases in the low-volume, medium-volume, and high-volume groups, overall adverse events were 10.0%, 7.6%, and 6.0%, transfusion rates were 1.3%, 1.1%, and 0.9%, and median postoperative stays were 12, 10, and 9 days, respectively. In multivariate analyses, compared with the low-volume group, medium-volume and high-volume groups were associated with a lower incidence of overall adverse events (odds ratio [OR] = 0.71, p = 0.058, and OR = 0.59, p = 0.013, respectively) and shorter postoperative stay (% difference = -10.5%, p = 0.023, and % difference = -18.5%, p = 0.001, respectively), while no significant association was detected for transfusion. Conclusions Less frequent adverse events and shorter stays were observed in higher-volume centers. Inverse volume-outcome relationships in PD catheter implantation were confirmed.

Resection of metastatic lesions (metastasectomy) is performed for highly selected patients with metastatic urothelial carcinoma (mUC). This study aimed to identify the clinicopathologic factors associated with oncologic outcome for patients who underwent metastasectomy for mUC. This analysis included 37 UC patients who underwent metastasectomy with curative intent at nine Japanese hospitals. The primary end point was cancer-specific survival. The Kaplan–Meier method with the log-rank test and the multivariable Cox proportional hazards model addressed the relationship between clinical characteristics and survival. Metastasectomy was performed for pulmonary (n = 23), nodal (n = 7), and other (n = 7) metastases. The median survival time was 35.4 months (interquartile range [IQR] 15.5, not reached) from the detection of metastasis and 34.3 months (IQR 13.1, not reached) from metastasectomy. The 5-year cancer-specific survival rate after detection of metastasis was 39.7%. In the multivariate analysis, the time from primary surgery to detection of metastasis (time-to-recurrence [TTR]) of 15 months or longer (hazard ratio [HR] 0.23; p = 0.0063), no symptoms of recurrence (HR 0.23; p = 0.0126), and serum C-reactive protein (CRP) levels lower than than 0.5 mg/dl (HR 0.24; p = 0.0052) were significantly associated with better survival. Long-term survival could be achieved for some patients with mUC who underwent metastasectomy. Lung and lymph nodes were predominant sites for metastasectomy. Symptoms, TTR, and CRP value were identified as associated with survival and should be taken into account when metastasectomy is considered.

Background To examine how surgical robot emergence affects prostate-cancer patient behavior in seeking radical prostatectomy focusing on geographical accessibility. Methods In Japan, robotic surgery was approved in April 2012. Based on data in the Japanese Diagnosis Procedure Combination database between April 2012 and March 2014, distance to nearest surgical robot and interval days to radical prostatectomy (divided by mean interval in 2011: % interval days to radical prostatectomy) were calculated for individual radical prostatectomy cases at non-robotic hospitals. Caseload changes regarding distance to nearest surgical robot and robot introduction were investigated. Change in % interval days to radical prostatectomy was evaluated by multivariate analysis including distance to nearest surgical robot, age, comorbidity, hospital volume, operation type, hospital academic status, bed volume and temporal progress. Results % Interval days to radical prostatectomy became wider for distance to nearest surgical robot

Our objective was to investigate predictors of early continence outcome after robot-assisted radical prostatectomy (RARP).Clinical records were prospectively collected in 272 patients who underwent RARP. Clinical parameters, continence rates, and time to achieve continence were investigated and analyzed. Recovery of continence was defined as achieving complete continence (pad-free).In the univariate analysis, young age (≤67 years) and low pT stage (≤pT2) were significantly associated with continence achieved within 2 weeks after RARP (P = 0.0343 and P = 0.0406, respectively). Low prostate weight was the only factor associated with recovery of continence within 1 month (P = 0.0461). Multivariate analysis revealed that young age (≤67 years) and low pT stage (≤pT2) were statistically significant predictors of continence within 2 weeks after RARP (P = 0.040 and P = 0.015, respectively).Young age and low pT stage were independent predictors of early continence.

In 2012, Japanese national insurance started covering robot-assisted surgery. We carried out a population-based comparison between robot-assisted and three other types of radical prostatectomy to evaluate the safety of robot-assisted prostatectomy during its initial year. We abstracted data for 7202 open, 2483 laparoscopic, 1181 minimal incision endoscopic, and 2126 robot-assisted radical prostatectomies for oncological stage T3 or less from the Diagnosis Procedure Combination database (April 2012–March 2013). Complication rate, transfusion rate, anesthesia time, postoperative length of stay, and cost were evaluated by pairwise one-to-one propensity-score matching and multivariable analyses with covariants of age, comorbidity, oncological stage, hospital volume, and hospital academic status. The proportion of robot-assisted radical prostatectomies dramatically increased from 8.6% to 24.1% during the first year. Compared with open, laparoscopic, and minimal incision endoscopic surgery, robot-assisted surgery was generally associated with a significantly lower complication rate (odds ratios, 0.25, 0.20, 0.33, respectively), autologous transfusion rate (0.04, 0.31, 0.10), homologous transfusion rate (0.16, 0.48, 0.14), lower cost excluding operation (differences, −5.1%, −1.8% [not significant], −10.8%) and shorter postoperative length of stay (–9.1%, +0.9% [not significant], –18.5%, respectively). However, robot-assisted surgery also resulted in a + 42.6% increase in anesthesia time and +52.4% increase in total cost compared with open surgery (all P < 0.05). Introduction of robotic surgery led to a dynamic change in prostate cancer surgery. Even in its initial year, robot-assisted radical prostatectomy was carried out with several favorable safety aspects compared to the conventional surgeries despite its having the longest anesthesia time and the highest cost.

Objective To assess the psychometric properties of the English version of the overactive bladder symptom score (OABSS) among overactive bladder (OAB) patients in the United States. Methods The reliability and validity of the OABSS were examined using data collected online from OAB patients residing in the United States. Results A total of 199 patients responded to the first questionnaire administration. Of those, 149 completed the second questionnaire. The results of the reliability assessment indicated that the intraclass correlation coefficient of the total OABSS score was 0.74 (weighted kappa coefficients of individual item score, 0.55-0.84) and that the Cronbach α coefficient was 0.56. In the analysis of the validity, the OABSS total score was correlated with all the external criteria (symptom bother of the overactive bladder questionnaire, patient perception of bladder condition, and International Prostate Symptom Score) to a moderate to strong degree. The results of known-group validity showed that the OABSS score tended to increase as the symptom severity increased (trend test; P Conclusion The present study demonstrated the reliability and validity of the English version of the OABSS. It is expected that the English version of the OABSS will be useful in clinical studies and medical practice among English-speaking OAB patients.

We report early experiences of contact laser vaporization of the prostate for symptomatic benign prostatic hyperplasia (BPH).A total of 80 patients recruited at four institutions in Japan from April 2013 through September 2014 underwent contact laser vaporization of the prostate using 980 nm high power diode laser with an end-firing fiber in the contact mode. Patients were followed prospectively at 1 day, 2, 4, 8, 12, and 24 weeks, postoperatively per protocol, and at 1 and 2 years post-protocol.Of 76 eligible patients, 64 (84.2%) achieved more than 50% decrease in International Prostate Symptom Score at 24 weeks (95% confidence interval: 74.0-91.6%), clearing the pre-fixed non-inferiority efficacy level to transurethral resection of the prostate (65%). Symptom scores, maximum flow rate, post-void residual urine, and prostate volume showed significant improvements at 12 and 24 weeks after the surgery. Perioperative complications included transient urinary retention (n = 20), retrograde ejaculation (5), bladder neck contracture (4), urethral stricture (3), stone in prostatic bed (3), bladder stone (2), bladder perforation (1), bladder deformity (1), and transient urgency incontinence (1). Urinary retention and bladder neck contracture occurred almost exclusively at one institution. Improved symptom scores, maximum flow rate, and post-void residual urine observed at 24 weeks remained virtually unchanged at 1 and 2 years.Early experience of contact laser vaporization in Japan showed efficacy comparable to transurethral resection of the prostate as a surgical procedure for BPH at 24 weeks. Long-term efficacy of the procedure remains uncertain.

PURPOSE To evaluate the effectiveness of computed tomography (CT) for detection of exit-site and tunnel infections with a Tenckhoff catheter. MATERIALS AND METHODS The study enrolled patients with exit-site or tunnel infections who underwent ultrasonography (US), CT scans, and subsequent catheter removal or partial catheter reimplantation from 2010 to 2014. Control cases on peritoneal dialysis who underwent abdominal CT scans for other reasons were randomly selected. Attenuation of the soft tissue around the Tenckhoff catheter was measured in Hounsfield units (HU). RESULTS 9 infected cases and 15 control cases were identified. CT showed increased attenuation around the catheter in all cases, while ultrasonography detected a hypoechoic area only in one case with abscess formation. Maximal attenuation of the inflamed soft tissue was high (median, 36 HU) compared with normal fatty tissue (median, -75 HU). In all cases, one or two sites with increased fat density were observed focally along the catheter, and these areas did not always extend directly from the exit site. CONCLUSIONS In this retrospective study comprising a small number of cases, increased attenuation of fatty tissue around the Tenckhoff catheter correlated with exit-site or tunnel infections. CT might be an auxiliary tool for diagnosis, although CT costs much more than US and is not always available in general practice. Further prospective studies are needed. .