Nesprin1 deficiency is associated with poor prognosis of renal cell carcinoma and resistance to sunitinib treatment.

INTRODUCTION: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC). METHODS: In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and Gene Set Enrichment Analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC. RESULTS: Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells, however, it did not influence the proliferation of cells. RNA sequencing and Gene Set Enrichment Analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival. CONCLUSIONS: The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment.

First reported human case of isolation of Vagococcus fluvialis from the urine of a former zoo clerk in Japan: a case report.

BACKGROUND: Vagococcal infections are extremely rare in humans. There are limited studies on the optimal methods for identification, antimicrobial susceptibility testing, and clinical manifestations of vagococcal infections. Herein, we report a patient with a urinary tract infection who had Vagococcus fluvialis in the urine. CASE PRESENTATION: An 84-year-old man presented to our urology department with a fever that had persisted for several days. He previously worked as a zoo clerk. The patient underwent a left nephroureterectomy for ureteral cancer 5 years ago, and total cystectomy and right cutaneous ureterostomy for muscle-invasive bladder cancer 1 year prior. He was empirically treated with 500 mg of levofloxacin intravenously every 24 h for the urinary tract infection. V. fluvialis was detected in his urine samples and Pseudomonas aeruginosa was detected in his urine and blood samples. Two bacterial species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. He was administered intravenous levofloxacin for approximately 1 week, followed by oral levofloxacin for another week, after which the infections were eradicated. CONCLUSIONS: To the best of our knowledge, this is the first report of V. fluvialis detected in human urine in Japan. Vagococcus spp. is commonly isolated from fish or animals, and based on the patient's work history, it is possible that the patient was a carrier because of transmission from animals.

Fourth national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from patients with complicated urinary tract infections.

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.

Preoperative high serum total testosterone levels predict preserved postoperative sexual function in patients after nerve-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To assess the association among preoperative total testosterone levels, postoperative sexual function, and prognosis after robot-assisted radical prostatectomy. METHODS: Patients who underwent robot-assisted radical prostatectomy in our institution were included in the study. Based on preoperative total testosterone levels, they were divided into low (<3.0 ng/mL) and high (≥3.0 ng/mL) total testosterone groups. Sexual function was evaluated using the International Index of Erectile Function scores, Expanded Prostate Cancer Index Composite scores, and the potency rate from preoperatively to 12 months after surgery. Oncological outcomes were evaluated based on biochemical recurrence. RESULTS: Out of 233 patients included, no significant difference in sexual function was found between the high (n = 183) and the low (n = 50) total testosterone groups at any point before or after surgery. However, in nerve-sparing cases, preservation in postoperative sexual function was observed only in the high total testosterone group (International Index of Erectile Function scores and Expanded Prostate Cancer Index Composite sexual function scores, at any point after surgery, p < 0.05; potency rate, at 3, 6, and 12 months after surgery; p < 0.05). Additionally, the high total testosterone group showed better biochemical recurrence-free survival than the low total testosterone group (p = 0.008). CONCLUSIONS: In the high total testosterone group, preservation in sexual function was observed after the nerve-sparing procedure, while the biochemical recurrence rate was low. Therefore, patients with high levels of total testosterone may be advised to consider nerve-sparing interventions.

Clinical characteristics and predictors of long-term postoperative urinary incontinence in patients treated with robot-assisted radical prostatectomy: A propensity-matched analysis.

OBJECTIVES: This study aimed to elucidate the clinical characteristics and predictors of long-term postoperative urinary incontinence (PUI) after robot-assisted radical prostatectomy (RARP). METHODS: This study included patients who underwent RARP at our institution and were stratified into PUI (≥1 pad/day) and continence (0 pad/day) groups at 60 months after RARP. A propensity score-matched analysis with multiple preoperative urinary status (Expanded Prostate Cancer Index Composite urinary subdomains, total International Prostate Symptom Score (IPSS), and IPSS-quality of life scores) was performed to match preoperative urinary status in these groups. Serial changes in urinary status and treatment satisfaction preoperatively and until 60 months after RARP were compared, and predictors of long-term PUI were assessed using multivariate logistic regression analysis. RESULTS: A total of 228 patients were included in the PUI and continence groups (114 patients each). Although no significant difference in preoperative urinary status was observed between the two groups, the postoperative urinary status significantly worsened overall in the PUI group than in the continence group. Treatment satisfaction was also significantly lower in the PUI group than in the continence group from 12 to 60 months postoperatively. Multivariate logistic regression analysis revealed that age (≥70 years) and biochemical recurrence (BCR) were significant predictors of the long-term PUI group (p < 0.05). CONCLUSIONS: Patients with long-term PUI had poor overall postoperative urinary status and lower treatment satisfaction than the continence group. Considering the age and risk of BCR is important for predicting long-term PUI when performing RARP.

BACH1 promotes clear cell renal cell carcinoma progression by upregulating oxidative stress-related tumorigenicity.

The carcinogenesis and progression of renal cell carcinoma (RCC), a heterogeneous cancer derived from renal tubular epithelial cells, is closely related to oxidative stress responses (OSRs). Oxidative stress responses participate in various biological processes related to the metabolism and metastatic potential of cancer such as inflammation, epithelial-mesenchymal transition (EMT), and angiogenesis. In this study, we investigated the role of broad complex-tramtrack-bric-a-brac and cap 'n' collar homology 1 (BACH1), a key transcription factor for OSRs, in clear cell RCC (ccRCC) development and prognosis. The poor prognosis and elevation of serum inflammation markers in nephrectomized ccRCC patients were correlated with the intratumor expression of BACH1 accompanied by a downregulation of heme oxygenase-1. BACH1 contributes to the invasion and migration abilities of RCC cell lines without affecting their proliferation in vitro. In contrast, BACH1 contributes to tumor progression in vivo, in relation to OSRs with the activation of EMT-related pathways. BACH1 involvement in other OSR-linked pathways, including inflammatory responses, angiogenesis, and mTOR signaling, was further revealed by RNA sequencing analysis of BACH1-knockdown cells. In conclusion, the crucial role of BACH1 in the pathogenesis and poor prognosis of ccRCC through the promotion of OSRs is suggested.

Impact of low and high body mass index on predicting therapeutic efficacy and prognosis in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

OBJECTIVE: To evaluate the significance of both low and high body mass index (BMI) as a biomarker in first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). METHODS: The oncological outcome of 235 patients with mRCC treated with TKI from 2007 to 2018 was reviewed retrospectively. All patients received first-line TKI as therapy. We analyzed the relationship between BMI (low and high) and disease control rate. The primary outcome was progression free survival and overall survival, and the association between BMI and survival prognosis was evaluated. RESULTS: The median BMI was 22.5 kg/m2 , and 25 patients (10.7%) had a low BMI (<18.5 kg/m2 ), 158 patients (67.2%) had a normal BMI (18.5-25 kg/m2 ), and 52 patients (22.1%) had a high BMI (≥ 25 kg/m2 ). Patients in the low BMI group had a significantly lower disease control rate, whereas patients in the high BMI group had a significantly higher disease control rate (p = 0.002 and p = 0.030, respectively). A log-rank test showed prognosis to be significantly poorer in the low BMI group and to be significantly better in the high BMI group than that in the normal BMI group. Multivariable Cox regression analysis showed that low BMI was an independent indicator of poor prognosis, whereas high BMI was an independent indicator of favorable prognosis. CONCLUSION: We showed the impact of both low and high BMI on predicting therapeutic efficacy and prognosis in mRCC patients treated with TKI.

Retrospective evaluation of the improvement in the urinary status-related quality of life after robot-assisted radical prostatectomy.

OBJECTIVES: This study aimed to investigate the characteristics of patients who report improvement in quality of life (QOL) related to urinary status after undergoing robot-assisted radical prostatectomy (RARP) for localized prostate cancer. METHODS: We retrospectively reviewed the patients who underwent RARP between May 2010 and May 2021 at our institution and were preoperatively unsatisfied with their urinary status. Patients were grouped as Group 1 (improved patients: "satisfied" with urinary status based on international prostate symptom score QOL [IPSS-QOL] = 0-2 at 12 months after RARP) and Group 2 (unimproved group: "unsatisfied"-IPSS-QOL 3-6). Additionally, the Expanded Prostate Cancer Index Composite (EPIC) urinary subdomains (urinary function, urinary bother [UB], urinary incontinence, and urinary irritation/obstruction [UIR]) and IPSS were evaluated preoperatively and till 12 months after RARP. RESULTS: Of the 237 patients, 72 (30.4%) were Group 1, and 165 (69.6%) were Group 2. Only UB and UIR improved at 12 months after RARP in Group 1, while other EPIC urinary subdomains remained unimproved at 12 months in both groups. On the other hand, IPSS improved at 12 months in both groups. Univariate and multivariate analysis revealed that the nerve-sparing, preoperative low IPSS (<11 vs. ≥11), and low IPSS-QOL (3 vs. 4-6) were associated with improvement in urinary status-related QOL (p < 0.05). CONCLUSIONS: Improvement in UB and UIR are important factors to ascertain improvement in urinary status-related QOL after RARP. Nerve-sparing and preoperative IPSS/IPSS-QOL values are useful predictors of this improvement.

Nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis from male urethritis in Japan: Comparison with the first surveillance report.

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 µg/ml (2 µg/ml), 1 µg/ml (0.5 µg/ml), 0.25 µg/ml (0.25 µg/ml), 0.125 µg/ml (0.063 µg/ml), 0.125 µg/ml (0.125 µg/ml), 0.25 µg/ml (0.25 µg/ml), 0.031 µg/ml (0.031 µg/ml), 0.25 µg/ml (0.125 µg/ml), and 0.016 µg/ml (0.008 µg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth.

Clinical characteristics of Actinotignum schaalii bacteremia in a Japanese tertiary hospital.

We retrospectively analyzed seven patients with Actinotignum schaalii bacteremia in a tertiary hospital in Japan. Pyelonephritis was the most frequent source of bacteremia, followed by Fournier's gangrene and pyometra. All patients with pyelonephritis had underlying urological conditions, ureteral stents, nephrostomy, ureteral stones, or ureterocele.

BUB1B Overexpression Is an Independent Prognostic Marker and Associated with CD44, p53, and PD-L1 in Renal Cell Carcinoma.

INTRODUCTION: BUB1 mitotic checkpoint serine/threonine kinase B encoded by BUB1B gene is a member of the spindle assembly checkpoint family. Several reports have demonstrated that overexpression of BUB1B is associated with cancer progression and prognosis. OBJECTIVE: This study aims to clarify the expression and function of BUB1B in renal cell carcinoma (RCC). METHODS: The expression of BUB1B was determined using immunohistochemistry and bioinformatics analysis in RCC. The effects of BUB1B knockdown on cell growth and invasion were evaluated. We analyzed the interaction between BUB1B, cancer stem cell markers, p53, and PD-L1 in RCC. RESULTS: In 121 cases of RCC, immunohistochemistry showed that 30 (25%) of the RCC cases were positive for BUB1B. High BUB1B expression was significantly correlated with high nuclear grade, T stage, and M stage. A Kaplan-Meier analysis showed that the high expression of BUB1B was associated with poor overall survival after nephrectomy. High BUB1B expression was associated with CD44, p53, and PD-L1 in RCC. Knockdown of BUB1B suppressed cell growth and invasion in RCC cell lines. Knockdown of BUB1B also suppressed the expression of CD44 and increased the expression of phospho-p53 (Ser15). In silico analysis showed that BUB1B was associated with inflamed CD8+, exhausted T-cell signature, IFN-γ signature, and the response to nivolumab. CONCLUSION: These results suggest that BUB1B plays an oncogenic role and may be a promising predictive biomarker for survival in RCC.

Indwelling catheterization, renal stones, and hydronephrosis are risk factors for symptomatic Staphylococcus aureus-related urinary tract infection.

PURPOSE: Staphylococcus aureus is a relatively uncommon causative agent of urinary tract infection (UTI). However, the clinical features of S. aureus-related UTI are unclear. Thus, we aimed to clarify how patients with S. aureus bacteriuria develop UTI and determine the features and clinical risk factors of symptomatic S. aureus-related UTI. METHODS: We performed a retrospective study of patients at the Hiroshima University Hospital for whom S. aureus had been isolated from urine culture from January 2010 to December 2017. The characteristics (age, sex, body mass index, indwelling catheterization, renal stones, hydronephrosis, anticancer drug use, diabetes mellitus, steroid use, serum albumin, antibiotic use in the past 1 month, estimated glomerular filtration rate, benign prostate hyperplasia, and neurogenic bladder) of patients with UTI and those without UTI were compared, and the risk factors for S. aureus-related UTI were identified by multiple logistic regression model. RESULTS: A total of 286 patients with S. aureus bacteriuria were analyzed; 33 patients developed UTI. The causative pathogens were methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MRSA) in 14 and 19 patients, respectively, who developed UTI. This study demonstrated that indwelling catheterization, hydronephrosis, and renal stones are significantly associated with S. aureus-related UTI (p = 0.01, odds ratio = 3.1; and p < 0.01, odds ratio = 7.0; and p = 0.02, odds ratio = 1.2; respectively) and hypoalbuminemia in MRSA-related UTI (p < 0.01). CONCLUSION: Paying attention to risk factors, specifically indwelling catheterization, renal stones, and hydronephrosis, will be an effective strategy for prevention of S. aureus-related UTI with persistent staphylococcal bacteriuria.

Nationwide surveillance of bacterial pathogens isolated from patients with acute uncomplicated cystitis in 2018: Conducted by the Japanese Research Group for Urinary Tract Infections (JRGU).

INTRODUCTION: The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data. METHODS: We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum ß-lactamase (ESBL) detection method. RESULTS: A total of 847 eligible cases were collected. Escherichia coli (E. coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E. coli (QREC) and ESBL-producing E. coli isolates at 15.6% and 9.5% of all E. coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S. saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E. coli, isolates from Eastern Japan had significantly higher susceptibility to cefazolin, cefotiam and cefpodoxime and lower susceptibility to levofloxacin in postmenopausal women. ESBL-producing E. coli isolates had a high susceptibility to tazobactam-piperacillin, cefmetazole, carbapenems, aminoglycosides, and fosfomycin. In S. saprophyticus, the susceptibility to ß-lactams including carbapenems was 40-60%. CONCLUSIONS: The proportions of QREC and ESBL-producing E. coli were increasing trends and lower susceptibility to LVFX in postmenopausal women was observed. Such surveillance, consisting of the collecting only clinical data, could be conducted easily and inexpensively. It is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains.

A Clinical Trial Evaluating the Usefulness of Tailored Antimicrobial Prophylaxis Using Rectal-culture Screening Media Prior to Transrectal Prostate Biopsy: A Multicenter, Randomized Controlled Trial.

The aim of this report is to introduce an on-going, multicenter, randomized controlled trial to evaluate whether tailored antimicrobial prophylaxis guided by rectal culture screening prevents acute bacterial prostatitis following transrectal prostate biopsy (TRPB). Patients will be randomized into an intervention or non-intervention group; tazobactam-piperacillin or levofloxacin will be prophylactically administered according to the results of rectal culture prior to TRPB in the intervention group whereas levofloxacin will be routinely given in the non-intervention group. The primary endpoint is the occurrence rate of acute bacterial prostatitis after TRPB. Recruitment begins in April, 2021 and the target total sample size is 5,100 participants.

Tumor contact length of prostate cancer determined by a three-dimensional method on multiparametric magnetic resonance imaging predicts extraprostatic extension and biochemical recurrence.

OBJECTIVE: To evaluate the clinical benefit of tumor contact length as a predictor of pathological extraprostatic extension and biochemical recurrence in patients undergoing prostatectomy. METHODS: A total of 91 patients who underwent 3T multiparametric magnetic resonance imaging before prostatectomy from April 2014 to July 2019 were included. A total of 94 prostate cancer foci were analyzed retrospectively. We evaluated maximum tumor contact length, which was determined to be the maximum value in the three-dimensional directions, as a predictor of pathological extraprostatic extension and biochemical recurrence. RESULTS: A total of 19 lesions (20.2%) had positive pathological extraprostatic extension. Areas under the curves showed maximum tumor contact length to be a significantly better parameter to predict pathological extraprostatic extension than the Prostate Imaging Reporting and Data System (P = 0.002), tumor maximal diameter (P = 0.001), prostate-specific antigen (P = 0.020), Gleason score (P < 0.001), and clinical T stage (P < 0.001). Multivariate analysis showed maximum tumor contact length (P = 0.003) to be an independent risk factor for predicting biochemical recurrence. We classified the patients using preoperative factors (prostate-specific antigen >10, Gleason score >3 + 4 and maximum tumor contact length >10 mm) into three groups: (i) high-risk group (patients having all factors); (ii) intermediate-risk group (patients having two of three factors); and (iii) low-risk group (patients having only one or none of the factors). Kaplan-Meier curves showed that the high-risk group had significantly worse biochemical recurrence than the intermediate-risk group (P = 0.042) and low-risk group (P < 0.001). CONCLUSIONS: Our findings suggest that maximum tumor contact length is an independent predictor of pathological extraprostatic extension and biochemical recurrence. A risk stratification system using prostate-specific antigen, Gleason score and maximum tumor contact length might be useful for preoperative assessment of prostate cancer patients.

TUBB3 Is Associated with High-Grade Histology, Poor Prognosis, p53 Expression, and Cancer Stem Cell Markers in Clear Cell Renal Cell Carcinoma.

BACKGROUND: ßIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. Several studies have shown that overexpression of TUBB3 is linked to poor prognosis and is involved in taxane resistance in some cancers. OBJECTIVE: The aim of this study was to analyze the expression and function of TUBB3 in clear cell renal cell carcinoma (ccRCC). METHODS: The expression of TUBB3 was determined using immuno-histochemistry in ccRCC specimens. The effects of TUBB3 knockdown on cell growth and invasion were evaluated in RCC cell lines. We analyzed the interaction between TUBB3, p53, cancer stem cell markers, and PD-L1. RESULTS: In 137 cases of ccRCC, immunohistochemistry showed that 28 (20%) of the ccRCC cases were positive for TUBB3. High TUBB3 expression was significantly correlated with high nuclear grade, high T stage, and N stage. A Kaplan-Meier analysis showed that high expression of TUBB3 was associated with poor overall survival after nephrectomy. In silico analysis also showed that high TUBB3 expression was correlated with overall survival. Knockdown of TUBB3 suppressed cell growth and invasion in 786-O and Caki-1 cells. High TUBB3 expression was associated with CD44, CD133, PD-L1, and p53 in ccRCC. We generated p53 knockout cells using the CRISPR-Cas9 system. Western blotting revealed that p53 knockout upregulated the expression of TUBB3. CONCLUSION: These results suggest that TUBB3 may play an oncogenic role and could be a potential therapeutic target in ccRCC.

Impact of radiological morphology of clinical T1 renal cell carcinoma on the prediction of upstaging to pathological T3.

OBJECTIVES: Previous studies have reported that cases with clinical T1 renal cell cancer upstaging to pathological T3 are a risk factor to predicting postoperative recurrence after partial nephrectomy. The aim of our study was to investigate the impact of the radiological morphology of the enhanced CT scan of clinical T1 renal cell cancer on predicting upstaging to pathological T3. METHODS: Three hundred sixty-seven cases with clinical T1 renal cell cancer diagnosed from enhanced CT scans were enrolled in this study. Based on the findings from the enhanced CT scan, the cases were classified into 'round', the margins of which were smooth and round; 'lobular', one or more findings of smooth dent and no spiky dent were identified on the margin of the tumor; and 'irregular', one or more spiky dent were identified on the margin of the tumor. The association of postoperative upstaging with these radiological morphology and other clinical characteristics of each case was analyzed. RESULTS: Eighteen cases (4.9%) pathologically upstaged to T3a. Two round case (0.7%), 3 lobular cases (10.0%) and 13 irregular cases (22.0%) pathologically upstaged (P < 0.001, round + lobular versus irregular). Four of 17 cases (23.5%) with hilar tumors pathologically upstaged, while 14 of 350 cases (4%) with tumors pathologically upstaged in other sites (P < 0.001). Multivariate analysis revealed that irregular case was an independent factor in predicting upstaging to pathological T3a (P < 0.001). CONCLUSIONS: Evaluation of the radiological morphology of clinical T1 renal cell cancer based on enhanced CT scans is useful for predicting pathological upstaging.

Magnetic resonance imaging/transrectal ultrasonography fusion targeted prostate biopsy finds more significant prostate cancer in biopsy-naïve Japanese men compared with the standard biopsy.

OBJECTIVE: To assess the clinical benefits of magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy for biopsy-naïve Japanese men. METHODS: Between February 2017 and August 2018, 131 biopsy-naïve men who underwent targeted biopsy together with 10-core systematic biopsy at Hiroshima University Hospital were retrospectively investigated. Multiparametric magnetic resonance imaging findings were reported based on Prostate Imaging Reporting and Data System version 2. RESULTS: The overall cancer detection rates per patient were 69.5% in systematic biopsy + targeted biopsy cores, 61.1% in systematic biopsy cores and 61.1% in targeted biopsy cores. The detection rates for clinically significant prostate cancer were 43.5% in targeted biopsy cores and 35.9% in systematic biopsy cores (P = 0.04), whereas the detection rates for clinically insignificant prostate cancer were 17.6% and 25.2% respectively (P = 0.04). Lesions in the peripheral zone were diagnosed more with clinically significant prostate cancer (54.8% vs 20.7%, P < 0.001) and International Society of Urological Pathology grade (3.2 vs 2.7, P = 0.02) than that in the inner gland. Just 4.2% (3/71) of Prostate Imaging Reporting and Data System category 2 and 3 lesions in the middle or base of the inner gland were found to have clinically significant prostate cancer. The cancer detection rate per core was 42.3% in targeted biopsy cores, whereas it was 17.9% in systematic biopsy cores (P < 0.001). CONCLUSIONS: Targeted biopsy is able to improve the diagnostic accuracy of biopsy in detection of clinically significant prostate cancer by reducing the number of clinically insignificant prostate cancer detections compared with 10-core systematic biopsy in biopsy-naïve Japanese men. In addition, the present findings suggest that patients with Prostate Imaging Reporting and Data System category 2 or 3 lesions at the middle or base of the inner gland might avoid biopsies.

Current status of countermeasures for infectious diseases and resistant microbes in the field of urology.

A worldwide increase in antimicrobial-resistant microbes due to the improper use of antimicrobial agents, along with a lack of progress in developing new antimicrobials, is becoming a societal problem. Although carbapenem-resistant Enterobacteriaceae, which are resistant to carbapenem antimicrobials, first appeared in 1993, treatment options remain limited. Mechanisms behind antimicrobial resistance involve changes to microbial outer membranes, drug efflux pump abnormalities, ß-lactamase production and the creation of biofilms around cell bodies. Genetic information related to these forms of antimicrobial resistance exists on chromosomes and plasmids, and when located on the latter can easily be transmitted to other strains, no matter the species, which creates a risk of antimicrobial resistance spreading exceptionally rapidly. To prevent the spread of antimicrobial resistance, the World Health Organization in 2015 published an action plan on antimicrobial resistance, based on which World Health Organization member countries have laid out specific policies and targets. Urinary tract infections are a type of healthcare-associated infection, and the sexually transmitted disease pathogen, Neisseria gonorrhoeae, has been included in a list of microbes that pose a risk to human health published by the US Centers for Disease Control and Prevention. Urologists face numerous problems when attempting to use antimicrobials properly, which is one method of dealing with antimicrobial resistance. Therefore, this article describes the current state of resistant microbes associated with urinary tract infections and countermeasures for antimicrobial resistance, including new antimicrobials.

The impact of change in serum C-reactive protein level on the prediction of effects of molecular targeted therapy in patients with metastatic renal cell carcinoma.

OBJECTIVES: To investigate the impact of pretreatment serum C-reactive protein (CRP) level and its change after targeted therapy on the anti-tumour effect of targeted agents in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: The serum CRP level in 190 cases of molecular targeted therapy for mRCC was measured before starting the prescription of molecular targeted agents and when computed tomography showed the maximum effect. Patients in which the pretreatment CRP level was ≥0.5 mg/dL were classified into a 'higher-CRP' group and others into a 'lower-CRP' group. The higher-CRP group was further classified into two subgroups, i.e. those whose serum CRP level decreased after molecular targeted therapy ('decreased-CRP' subgroup), and those whose level did not decrease after therapy ('non-decreased-CRP' subgroup). All patients were also classified according to their other clinical details and progression-free survival (PFS) rates of each subgroup were compared. RESULTS: Of the 190 patients, 97 were categorised as lower CRP and 93 as higher CRP, with 50 and 43 patients in the higher-CRP group further categorised as decreased- and non-decreased-CRP subgroups, respectively. For the maximum effects of the targeted therapy, determined based on the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, in the lower-CRP group, significantly more patients had a complete response (CR) and partial response (PR) (P = 0.002) and significantly fewer had progressive disease (PD) (P < 0.001) vs the higher-CRP group. In the higher-CRP group, significantly fewer patients had PD in the decreased-CRP subgroup (P < 0.001) than those in the non-decreased-CRP subgroup. The 2-year PFS rate for the lower-CRP group (39.1%) was significantly better vs the decreased-CRP subgroup (21.2%; P = 0.013) and significantly better vs the non-decreased CRP subgroup (0%; P < 0.001). Multivariate analyses in the higher-CRP group revealed that decreased CRP was an independent predictive factor for PFS (P = 0.002, hazard ratio 2.454, 95% confidence interval 1.404-4.290). CONCLUSION: A decrease of CRP and pretreatment CRP levels show promise as a novel predictive factor for anti-tumour effects in patients treated with molecular targeted therapy.