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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 β-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., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K. K., Fujirebio Inc., and Abbott Japan Co., Ltd. Koichiro Wada received speaker honoraria from Janssen Pharmaceutical K.K., and MSD K.K. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Tohru Nakagawa received speaker honoraria from Astellas Pharma Inc., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum β-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan., Competing Interests: Declaration of competing interest Koichiro Wada received speaker honoraria from Janssen Pharmaceuticals, Inc. Satoshi Takahashi received speaker honoraria from Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Shin Ito received research funding from Hologic, Inc., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were β-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from MSD K.K., Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Hiroyuki Nishiyama received research funding from Chugai Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Junichi Inokuchi received research funding from Chugai Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the UPOINT-positive domain numbers and evaluate the significance of the sexual dysfunction domain in patients with chronic prostatitis or chronic pelvic pain (CP/CPPS) in Japan., Methods: A total of 58 patients with CP/CPPS with moderate or greater symptoms were included. Symptom severity was determined by > 14 on the chronic prostatitis symptom index (CPSI). The main outcome was to confirm the number and distribution of the positive UPOINT domains in this group. As secondary outcomes, the correlation between positive domain numbers and CPSI scores was evaluated. We also examined whether the sexual dysfunction subdomain, as determined by the five-item international index of erectile function, could improve the correlation with symptom severity., Results: The mean age was 48.6 ± 15.4 years, CPSI score 24.3 ± 6.1, and positive UPOINT domain number 2.4 ± 0.9. The distribution of each positive domain was 67.2% for urinary, 15.5% for psychosocial, 75.8% for organ-specific, 3.4% for infection, 5.1% for neurological/systemic conditions, and 75.8% for tenderness. Although the mean CPSI total scores tended to increase with an increasing number of positive UPOINT domains, a significant correlation was not observed (r = 0.134, p = 0.312). The sexual dysfunction domain was positive in 62.0% of the cases, but the correlation could not be improved., Conclusions: Urinary, organ specific, and tenderness domains were mainly observed in patients with CP/CPPS. When patients with moderate or grater CPSI scores are clinically evaluated, clinicians should recognize that the UPOINT-positive domain and CPSI score are clinically and pathologically different concepts. (250 words)., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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 (MIC 90 ) 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., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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 β-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 β-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., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Men and women have specific patterns in an electrocardiogram (ECG) differentiated by J-point elevation and ST-segment angle. Although gender-affirming hormone treatment is one of the treatments for gender dysphoria, its influence on an ECG has not been clarified yet., Objective: The purpose of this study was to investigate ECG changes induced by gender-affirming hormone treatment., Methods: The study population consisted of 29 transgender males and 8 transgender females and 37 age- and sex-matched cisgender females and males. Male pattern was defined as J-point elevation > 0.1 mV and ST-segment angle > 20° in precordial leads., Results: In the comparison between 29 transgender males and cisgender females, the prevalence of the male pattern (89.7% vs 6.9%; P < .001), prevalence of the early repolarization pattern (51.7% vs 17.2%; P = .01), J-point elevation (leads V 1 -V 6 ), T-wave amplitudes (leads V 1 -V 6 ), QRS amplitudes (leads II, III, V 1 -V 6 ), and P-wave amplitudes (leads V 1 -V 3 ) were significantly higher in transgender males. The prevalence of the male pattern was lower in transgender females than in cisgender males (25.0% vs 87.5%; P = .04). In the analysis of transgender males for whom ECGs were available before and after gender-affirming hormone treatment (n = 13), J-point elevation and T-wave amplitudes significantly increased after gender-affirming hormone treatment, leading to a higher prevalence of the male pattern (23.1% vs 92.3%; P < .001). The prevalence of the early repolarization pattern and QRS amplitudes also significantly increased after the treatment, but the augmentation of P-wave amplitudes was modest., Conclusion: Gender-affirming hormone treatment for gender dysphoria is accompanied by a change in ECG phenotype toward affirming gender, in which change in androgen level may be involved., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Previously, we investigated gene expression in a high aldehyde dehydrogenase 1 expression (ALDH1 high ) population of urothelial carcinoma (UC) cells as UC cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) and found that NRG1 expression was upregulated in ALDH1 high cells. NRG1 is a trophic factor that contains an epidermal growth factor (EGF)-like domain that signals by stimulating ERBB receptor tyrosine kinases and the cytoplasmic domain. NRG1 has been determined to be involved in frequent gene fusions with other partners in several malignancies and has a role in carcinogenesis through the NRG1 EGF-like domain and its cognitive receptor ERBBs. We thus aimed to elucidate the function of NRG1 in UC CSCs/CICs in this study. Both NRG1α and NRG1-β1 were preferentially expressed in ALDH1 high cells compared with ALDH1 low cells; however, siRNA experiments revealed that NRG1-β1 but not NRG1-α has a role in sphere formation. The EGF-like domain of NRG1 had a role in sphere formation of UC cells to some extent but was not essential. The intracellular domain of NRG1 did not have a role in sphere-formation. Inhibition of γ-secretase suppressed sphere formation. These findings indicate that cleavage of NRG1-β1 by γ-secretase plays an important role in UC CSC/CIC proliferation; however, the downstream targets of NRG1-β1 remain elusive., Competing Interests: Declaration of competing interest The authors have no financial conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Eradication of asymptomatic bacteriuria (ASB) before urological procedures is important to reduce the risk for infectious complications after surgery. However, the appropriate regimen for antimicrobial treatment has not been fully determined. We experienced continuous (over 10 months) isolation of extended spectrum β-lactamase (ESBL)-producing fluoroquinolone-resistant Escherichia coli from urine of an asymptomatic patient. The four isolates obtained (SMESC1 to 4) were international high-risk clones of O25b:H4-ST131-H30R, and originated from one strain, as revealed by the whole genome sequences. Although the patient received meropenem (MEPM) and fosfomycin (FOM), to which the strains were susceptible before the urological procedures, they could not be eradicated., Methods: To explore the reason for the continuous isolation even after MEPM and FOM administration, antimicrobial killing of adherent and/or intracellular bacterial communities (IBC) formed by coculture of the E. coli cells and T24 bladder epithelial cells were examined., Results: FOM and levofloxacin did not decrease viable E. coli cells compared with gentamicin. MEPM partly decreased them, and sitafloxacin (STFX) decreased them most potently. These observations indicate that E. coli can survive in the urinary tract under antimicrobial administration, and some antimicrobials such as FOM and MEPM cannot eradicate E. coli in uroepithelial cells. Adhesion on urinary epithelial cells and/or IBC formation might result in continuous isolation from the urinary tract and recurrence of ASB and urinary tract infections., Conclusions: The present study suggests that STFX is a promising optional agent for the eradication of ESBL-producing fluoroquinolone-resistant E. coli in the urinary tract before urological procedures., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from DaiichiSankyo Company and research grants from Shino-Test Corporation and Abbott Japan Co., Ltd., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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 MIC 90 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., Competing Interests: Declaration of Competing Interest Shingo Yamamoto has received speaker's honorarium from Daiichi Sankyo Co., Ltd., and scholarship donations from Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd, Pfizer Japan Inc., and Bayer Yakuhin, Ltd. Satoshi Takahashi has received speaker honoraria from Daiichi Sankyo Co., Ltd. and MSD K.K., and research grants from Shino-Test Corporation and Abbott Japan Co., Ltd. Ryoichi Hamasuna has received speaker's honorarium from Daiichi Sankyo Co. Ltd. Shinichiro Minamitani is an employee of Daiichi Sankyo Co., Ltd. Tetsuya Matsumoto has received speaker's honorarium from MSD K.K. and Pfizer Japan Inc. Hiroshi Kiyota and Hiroki Yamada have received scholarship donations from Taisho Toyama Pharmaceutical Co., Ltd., Toyama Chemical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., Taiho Pharmaceutical Co., Ltd., and Sanofi K.K. Kazuhiro Tateda received speaker honoraria from Pfizer Japan Inc., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. and Meiji Seika Pharma Co., Ltd., research funding from Meiji Seika Pharma Co., Ltd., Nippon Becton Dickinson Company, Ltd., Asahi Kasei Pharma Corporation, Eidia Co., Ltd., Eiken Chemical Co. Ltd., Nissui Pharmaceutical Co., Ltd., Spero OpCo, Inc., Shimadzu Corporation, Hitachi Ltd., Kyorin Pharmaceutical Co., Ltd., MSD K.K., Denka Company Limited, KD-ICONS Co. Ltd., and grant support from Taisho Toyama Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Asahi Kasei Pharma Corporation, Shionogi & Co., Ltd., Meiji Seika Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Astellas Pharma Inc., and FUJIFILM Toyama Chemical Co., Ltd., and scholarship donations from Taisho Toyama Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Asahi Kasei Pharma Corporation, Shionogi & Co., Ltd., Meiji Seika Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Astellas Pharma Inc. and FUJIFILM Toyama Chemical Co., Ltd., and has an endowed department sponsored by Meiji Seika Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Astellas Pharma Inc., Taisho Toyama Pharmaceutical Co., Ltd., MSD K.K. and Daiichi Sankyo Co., Ltd. Hiroyuki Nishiyama has received speaker's honorarium from MSD K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd. and Astellas Pharma Inc., research funding from Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd. and Chugai Pharmaceutical Co., Ltd., and scholarship donations from Astellas Pharma Inc., Novartis Pharma K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Our aim was to evaluate the usefulness of serum testosterone to guide treatment decision for castration-resistant prostate cancer (CRPC)., Methods: We conducted a retrospective analysis of 115 patients with CRPC treated with either abiraterone (n = 43) or enzalutamide (n = 72). A serum testosterone level was measured at time of starting of abiraterone or enzalutamide. We determined whether serum testosterone influenced the outcomes of androgen receptor (AR)-targeted therapy., Results: In the very-low testosterone group (<5 ng/dl), the rate of prostate-specific antigen (PSA) response was significantly higher among patients treated with abiraterone compared to enzalutamide (62 vs. 32%, respectively; P = 0.033), with no difference in the low testosterone group (5-<50 ng/dl) (93 vs. 81%, respectively; P = 0.429). During the median follow-up of 26 months, PSA progression-free survival was significantly longer in the low testosterone group than in the very-low testosterone group (12.2 vs. 4.5 months, P<0.001). In the very-low testosterone group, enzalutamide use (HR 3.07, 95% CI 1.36-6.94; P = 0.007), primary androgen deprivation therapy <12 months (HR 2.50, 95% CI 1.23-5.08; P = 0.011) and bone metastases (HR 2.60, 95% CI 1.20-5.64; P = 0.015) were significantly associated with PSA progression., Conclusion: Patients with a serum testosterone level ≥5 ng/dl were more likely to receive therapeutic benefits from AR-targeted therapy compared to those with serum testosterone levels <5 ng/dl. However, even for those with a very low serum testosterone level, the efficacy of abiraterone was slightly higher than that of enzalutamide. Therefore, serum testosterone level is a useful biomarker for informing treatment selection for CRPC., (Copyright © 2019. Published by Elsevier Inc.)

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16-40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the impact of the risk group disagreement between the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models on prognosis., Patients and Methods: We retrospectively evaluated 176 patients with metastatic renal-cell carcinoma who were treated with tyrosine kinase inhibitors as first-line therapy in 5 hospitals between October 2008 and August 2018. The risk group classification differences between the MSKCC and the IMDC models were evaluated using criteria of agreement (identical risk group in both the MSKCC and IMDC models) and disagreement (not identical risk group in both the MSKCC and IMDC models). The agreement of risk stratification between the models was evaluated using the Cohen κ coefficient. Oncologic outcomes were compared between the agreement and disagreement groups., Results: The number of patients with agreement, upgrade, and downgrade was 135 (77%), 39 (22%), and 2 (1.1%), respectively. Of 41 patients with disagreement, reclassification from the MSKCC-intermediate to the IMDC-poor risk group was most frequent (n = 34, 19%). The Cohen κ coefficient for agreement was substantial, with κ = 0.613 (P < .001). Significantly poorer prognosis was observed in patients with disagreement than in those with agreement. Neutrophil count, hemoglobin, serum calcium concentration, and C-reactive protein were significantly different between the groups., Conclusion: Disagreement between the MSKCC and IMDC models may have a negative impact on prognosis in patients with metastatic renal-cell carcinoma. The inclusion of systematic inflammation markers in a risk model may be essential for prognosis prediction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Standard treatments have not been established in metastatic papillary renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in patients with mPRCC., Patients and Methods: This study included 51 patients who were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by pathologists. The associations between clinical factors and overall survival (OS) were analyzed., Results: Final pathologic diagnoses could be determined in 50 patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15 were diagnosed as other histologic types. Targeted therapies (TTs) were provided to 25 mPRCC patients. Patients treated with TT survived significantly longer than those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035). Median OS of patients who experienced stable disease for ≥ 9 months using single TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as first-line TT survived longer after TT initiation than those treated with an mTOR inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs in both first- and second-line settings had significantly better survival after TT initiation than those treated with a TKI in one therapy line and an mTOR inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a TKI as second-line TT survived significantly longer after second-line TT initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P = .0016)., Conclusion: Prognoses of patients with mPRCC were improved by TT, and TKIs appeared to be the treatment of choice in both the first- and second-line settings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to clarify the prognostic indicators for upper tract urothelial carcinoma (UTUC) following intravesical bacillus Calmette-Guérin (BCG) therapy for nonmuscle-invasive bladder cancer (NMIBC)., Methods: Data from 402 patients who received intravesical BCG therapy between January 1990 and November 2011 were collected from 10 institutes. The median follow-up interval from transurethral resection of the bladder tumor (TURBT) followed by BCG treatment was 50.0 months (IQR: 31.8-77.0). Of these patients, 186 (46.3%) had intravesical recurrence during the follow-up period after BCG therapy., Results: Thirty patients (7.5%) were diagnosed with UTUC after BCG therapy. The 10-year recurrence-free survival rates for UTUC (RFS-UTUC) was 87.5%. In univariate and multivariate analyses, the independent predicting factors for UTUC were intravesical recurrence (P = 0.016) and tumor morphology at TURBT before BCG (P = 0.045). The 10-year RFS-UTUC of patients with intravesical recurrence and others, were 80.6% and 95.0%, respectively. The 10-year RFS-UTUC of patients with papillary pedunculated tumors and nonpapillary or nonpedunculated were 96.1% and 84.6%, respectively., Conclusions: The frequency of UTUC in patients with NMIBC after BCG therapy is not negligible. Two independent predicting factors (intravesical recurrence and nonpapillary nonpedunculated at TURBT before BCG) were identified for UTUC. These results might be useful to predict UTUC after BCG therapy for NMIBC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The number of patients with acute cystitis caused by extended spectrum β lactamase (ESBL)-producing Escherichia coli (E. coli) is increasing gradually. Although it is reported that ESBL-producing E. coli are sensitive to faropenem (FRPM), there are few clinical studies on the efficiency of FRPM against acute cystitis caused by the bacteria. Therefore, we retrospectively reviewed the medical charts of patients with acute cystitis caused by ESBL-producing E. coli who were treated with the oral antimicrobial agent faropenem (FRPM) in our institution from June 2011 to May 2015. Ten patients with acute cystitis caused by ESBL producing E. coli were treated with FRPM. Although clinical cure was achieved in 9 of them, it reoccurred in 3. This study revealed that the treatment regimen with FRPM for patients with acute cystitis caused by ESBL-producing E. coli is promising. However, a non-negligible number of recurrences were caused by ESBL-producing E. coli because of the nature of underlying diseases or pathologies in the urinary tract., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We report a patient with infective endocarditis and pyrogenic spondylitis occurring simultaneously. The patient was a 59-year-old man. He was suspected of having prostate cancer due to a high prostate-specific antigen concentration noted in a checkup. He then underwent a transrectal ultrasound guided prostate biopsy with cefotiam as antimicrobial prophylaxis. He had a fever higher than 38 °C and lumbar pain for a few days after the biopsy. Enterococcus faecalis was isolated from 2 sets of blood culture. Magnetic resonance imaging revealed an abnormal image at C7/Th1 with a signal decrease in T1-weighted sequences and signal increase in T2-weighted sequences that were suspected to be due to bone destruction. Therefore, he was diagnosed as having pyogenic spondylitis by an orthopedist. At the same time, he complained of palpitation and a heart murmur was detected. Then transesophageal echocardiography was performed by a cardiologist and it revealed vegetation in his left ventricle and aortic regurgitation, and finally acute cardiac insufficiency was determined. He was treated with tazobactam/piperacillin and aortic valve displacement surgery. Based on the results of the prostate biopsy and image inspection, he was diagnosed as having localized prostate cancer. He was treated by androgen deprivation therapy and external beam radiation therapy. We have to keep in mind that E. faecalis can be a potential pathogen for severe infectious complications after prostate biopsy, especially if a cephalosporin is selected for antimicrobial prophylaxis., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Genital chlamydial infection is a principal sexually transmitted infection worldwide. Chlamydia trachomatis can cause male urethritis, acute epididymitis, cervicitis, and pelvic inflammatory disease as sexually transmitted infections. Fortunately, homotypic resistant C. trachomatis strains have not been isolated to date; however, several studies have reported the isolation of heterotypic resistant strains from patients. In this surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 51 hospitals and clinics in 2009 and 38 in 2012. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 19 isolates in 2009 and 39 in 2012. In 2009 and 2012, the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, and azithromycin were 2 μg/ml and 1 μg/ml, 0.5 μg/ml and 0.5 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.063 μg/ml and 0.063 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.016 μg/ml and 0.016 μg/ml, and 0.063 μg/ml and 0.063 μg/ml, respectively. In summary, this surveillance project did not identify any resistant strain against fluoroquinolone, tetracycline, or macrolide agents in Japan., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

While the incidence of antibody-mediated kidney graft rejection has increased, the key cellular and molecular participants underlying this graft injury remain unclear. Rejection of kidney allografts in mice lacking the chemokine receptor CCR5 is dependent on production of donor-specific antibody. Here we determine if cells expressing cytotoxic function contributed to antibody-mediated kidney allograft rejection in these recipients. Wild-type C57BL/6, B6.CCR5(-/-), and B6.CD8(-/-)/CCR5(-/-) mice were transplanted with complete MHC-mismatched A/J kidney grafts, and intragraft inflammatory components were followed to rejection. B6.CCR5(-/-) and B6.CD8(-/-)/CCR5(-/-) recipients rejected kidney allografts by day 35, whereas 65% of allografts in wild-type recipients survived past day 80 post-transplant. Rejected allografts in wild-type C57BL/6, B6.CCR5(-/-), and B6.CD8(-/-)/CCR5(-/-) recipients expressed high levels of VCAM-1 and MMP7 mRNA that was associated with high serum titers of donor-specific antibody. High levels of perforin and granzyme B mRNA expression peaked on day 6 post-transplant in allografts in all recipients, but were absent in isografts. Depletion of natural killer cells in B6.CD8(-/-)/CCR5(-/-) recipients reduced this expression to background levels and promoted the long-term survival of 40% of the kidney allografts. Thus, natural killer cells have a role in increased inflammation during antibody-mediated kidney allograft injury and in rejection of the grafts., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

One of the major complications of clean intermittent catheterization (CIC) is urinary tract infection (UTI). Recent reports showed that community-acquired UTIs caused by antimicrobial-resistant pathogens were gradually presenting in adults. However, there have been few reports about UTIs caused by antimicrobial-resistant bacteria in pediatric patients. Therefore, we retrospectively reviewed the medical charts of 45 children with CIC due to neurogenic bladder dysfunction from January 2010 to March 2013. Sixty-two episodes of cystitis occurred in 27 patients. Seventy bacterial strains were isolated from urine samples. The rate of Gram-negative bacteria was 84.3%. Six extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) strains were isolated from 4 patients. An ESBL-producing Proteus mirabilis strain and a methicillin-resistant Staphylococcus aureus strain were isolated from one patient each. Most of the pathogens of cystitis in the pediatric patients with CIC were Gram-negative bacilli, especially E. coli. We should be aware that ESBL producing E. coli as potential pathogens cause cystitis and regularly survey antimicrobial susceptibility to understand the resistant strains that develop., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

To evaluate the current methods of surgical antimicrobial prophylaxis from the viewpoint of pharmacokinetics for patients undergo urologic surgery, this study was designed to measure the serum concentrations of two different prophylactic antimicrobial agents in different types of urologic surgery. This prospective study included 39 patients with prostate cancer, renal pelvic cancer, ureteral cancer or renal cancer treated by radical surgery from August 2005 to March 2006. Blood samples were taken intraoperatively at 30 min and 180 min after the beginning of the first administration. The half-life of the beta phase of cefazolin is 2.46 h and that of piperacillin is 0.7 h according to their manufacturers. The average serum concentration of cefazolin at 30 min was 144 μg/mL in the prostatectomy group and 175 μg/mL in the nephrectomy group. At 180 min, the average concentration of cefazolin was 37 μg/mL in prostatectomy group and 59 μg/mL in the nephrectomy group. The average concentration of piperacillin at 30 min was 134 μg/mL in the prostatectomy group and 137 μg/mL in the nephrectomy group. At 180 min, the average concentration of piperacillin was 10 μg/mL in the prostatectomy group and 22 μg/mL in the nephrectomy group. Thus, the concentration at 180 min after the beginning of infusion was different according to the half-life of each antimicrobial agent. Therefore, up-to-date guidelines for surgical antimicrobial prophylaxis that deal with additional types of intraoperative prophylaxis should be consulted if the operation exceeds two half-lives of the prophylactic antimicrobial agents used in real-life clinical practice., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

To clarify the discrepancy in the incidence and severity of surgical site infections (SSI) for radical cystectomy between reports based on the CDC guideline and those using the Clavien-Dindo classification we evaluated 449 consecutive patients who underwent radical cystectomy for bladder cancer between 1990 and 2012. Of the 115 (25.6%) patients with SSI defined by the CDC guideline, 89 could be analyzed. We compared the SSI rates and severity defined by the CDC guideline and Clavien-Dindo classifications. There were 58 patients with superficial SSI, 16 with deep SSI, and 15 with organ/space SSI according to the CDC guideline. All patients with organ/space SSI were judged as "not having SSI" by the Clavien-Dindo classification. They were classified as having "intestinal prolapse", "intestinal fistula", "abdominal abscess" and "pelvic abscess." There was a significant association between the treatment duration and depth of SSI based on the CDC guideline by Spearman's rank-correlation coefficient (p < 0.001, r = 0.614) and with the grade of complications (p < 0.001, r = 0.632) in the Clavien-Dindo classification. Multivariate analysis showed that patients with grade III SSI in the Clavien-Dindo classification needed a significantly longer treatment duration. It is necessary to be aware that a discrepancy can occur automatically due to the different natures of the definitions. Using the CDC guideline, we can effectively estimate the future treatment period when SSI occurs. With the Clavien-Dindo classification, grade III SSI requires a longer treatment duration., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

There is still controversy about whether post-void residual (PVR) urine volume affects the onset of urinary tract infection (UTI). In addition, although male patients with lower urinary tract symptoms (LUTS) might potentially have PVR, the association between LUTS and UTI or asymptomatic pyuria with or without bacteriuria remains unclear. We studied the frequency of asymptomatic pyuria, with and without bacteriuria, in patients with LUTS without a previous history of urinary tract manipulation at the first visit and their sequential courses. This retrospective study was done by reviewing medical charts. A total of 453 male patients who complained of LUTS and visited our outpatient clinic in 2008 were included in this study. The frequency of pyuria, with or without bacteriuria, in this study at the first visit was 4.9%. The median PVR volumes at the initial examination were 79 ml in the 22 patients with pyuria and 22 ml in the 431 patients without pyuria. The difference of the PVR volume between the patients with pyuria and those without pyuria was statistically significant (p = 0.0095). Twelve patients were treated with alpha-blockers without antimicrobial chemotherapy and pyuria disappeared in 5 (41.7%) of them. However, the decrease in the rate of PVR was not significantly different between the patients with persisting pyuria and those without pyuria. A not negligible number of patients with LUTS had pyuria at the first visit; however, there was no febrile UTI in their clinical course even if they received no urological manipulation., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: This study aimed to determine the clinical benefit of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy., Patients and Methods: Patients with MIBC (T2-4aN0M0) were randomised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy (NAC arm) or radical cystectomy alone (RC arm). The primary end point was overall survival (OS). Secondary end points were progression-free survival, surgery-related complications, adverse events during chemotherapy, proportion with no residual tumour in the cystectomy specimens, and quality of life. To detect an improvement in 5-year OS from 45% in the RC arm to 57% in the NAC arm with 80% power, 176 events were required per arm., Results: Patients (N = 130) were randomly assigned to the RC arm (N = 66) and the NAC arm (N = 64). The patient registration was terminated before reaching the initially planned number of patients because of slow accrual. At the second interim analysis just after the early stoppage of patient accrual, the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion. OS of the NAC arm was better than that of the RC arm, although the difference was not statistically significant [hazard ratio 0.65, multiplicity adjusted 99.99% confidence interval 0.19-2.18, one-sided P = 0.07]. In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively (P < 0.01). In subgroup analyses, OS in almost all subgroups was in favour of NAC., Conclusions: This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC. NAC with MVAC can still be considered promising as a standard treatment., Umin Clinical Trials Registry Identifier: C000000093., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To clarify the incidence of surgical site infection (SSI) after urological scrotal and inguinal surgical procedures and the preventive effect of antimicrobial prophylaxis for SSI, retrospective analysis was performed. The patients who underwent scrotal and inguinal operations from 2001 to 2010 were included in this analysis. A first or second generation cephalosporin was administered as antimicrobial prophylaxis just before the start of surgery and no additional prophylaxis was conducted. The surgery was classified into 76 (38%) cases with testicular sperm extraction (TESE), 72 (36%) with radical orchiectomy, 29 (14.5%) with bilateral orchiectomy (surgical castration) and 23 (11.5%) with other scrotal and inguinal operations. The median age and age range were 36 years and 18-81 years, respectively. SSI occurred in 7 (3.5%) cases. The frequencies of SSI were 6.5% in the patients with urological inguinal surgery and 1.6% in those with scrotal surgery. The frequency of SSI in the patients with urological inguinal surgery was not negligible even though it is considered a clean operation, and further analysis is warranted to prevent SSI., (Copyright © 2013 Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Context: Chemotherapy-induced nausea and vomiting (CINV) can severely impair patients' quality of life (QOL). Psychotropics, especially olanzapine, have a strong antiemetic effect., Objectives: To determine whether olanzapine could reduce the frequency of CINV and improve patients' QOL during chemotherapy., Methods: This was a randomized, double-blind, placebo-controlled trial. Forty-four patients scheduled to receive highly or moderately emetogenic chemotherapy were enrolled. All patients received a 5-hydroxytryptamine3 receptor antagonist, steroid, and neurokinin-1 receptor antagonist. Patients were randomly assigned to take 5 mg/day of oral olanzapine (OL group, n = 22) or placebo (control group, n = 22) daily from the day before chemotherapy (Day 0) to Day 5. The primary endpoint was the rate of patients who achieved total control (no vomiting, no use of rescue medications, and maximum nausea of <5/100mm on a visual analogue scale). The secondary endpoint was Functional Living Index-Emesis questionnaire score on Days 0 and 6., Results: The rate of patients achieving total control was significantly higher in the OL group (86% and 64% in acute and delayed phases, respectively) than in the control group (55% and 23%, P = 0.045, P = 0.014, respectively). Furthermore, the OL group experienced a better QOL than the control group, as reported on the Functional Living Index-Emesis questionnaire (P = 0.0004)., Conclusion: The addition of 5mg/day of oral olanzapine to standard therapy can reduce the frequency of CINV and improve QOL of patients receiving highly or moderately emetogenic chemotherapy., (Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Radical cystectomy followed by urinary diversion or reconstruction (RC) is a standard treatment for patients with muscle-invasive bladder cancer. In these operations, a high frequency of complications, especially postoperative infection, has been reported. However, there have only been a few studies about postoperative anaerobic bacterial infection. To clarify the significance and role of anaerobic bacteria in postoperative infection, we retrospectively analyzed cases in which postoperative infection by these organisms developed. A total of 126 patients who underwent RC from 2006 to 2010 were included in this study. Various types of postoperative infection occurred in 66 patients. Anaerobic bacterial infections were detected with cultures for urine and blood in one case, for blood in two cases, and for surgical wound pus in four. The frequency of postoperative anaerobic bacterial infection in RC was less than that of colon surgery. However, this study revealed the possible development of a nonnegligible number of postoperative anaerobic bacterial infections. Therefore, we should consider anaerobic bacteria as possible pathogens in postoperative infection after RC.

A 67-year-old woman diagnosed with pyonephrosis and perinephric abscess because of an impacted urinary stone in the pelvicoureteric junction was admitted to the hospital with a high-grade fever. Although construction of a right nephrostomy for drainage of the abscess improved her general condition, she had a fever again 2 weeks after the initial treatment. Computed tomography revealed a persistent perinephric retroperitoneal abscess and a second drainage procedure was performed. Then, imaging examination revealed fistula formation between the cavity of the perinephric retroperitoneal abscess and the duodenum. The patient received conservative management including percutaneous drainage, discontinuation of oral intake, and antimicrobial chemotherapy. Three days after the second drainage and discontinuation of oral intake, imaging examination revealed complete closure of the fistula. Fistula formation between a perinephric abscess and the duodenum is very rare but a favorable outcome was obtained by our conservative management.

We previously reported that the incidence of surgical site infection (SSI) after radical cystectomy was 33% between January 1996 and December 2003 at Sapporo Medical University Hospital. Base on that result, we modified perioperative management for surgical wounds after January 2004. The modifications included the method of suturing and standardization of the period for removal of closed drains and surgical dressings. This study compared the incidence of SSI between the former and latter periods, and assessed risk factors for SSI. The study consisted of 109 patients between January 1996 and December 2003 (Group A), and 104 patients between January 2004 and December 2007 (Group B), who underwent radical cystectomy and urinary diversion or reconstruction. The incidence of SSI was reduced from 32.1% in Group A to 18.2% in Group B (p = 0.027). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from SSI wounds in 40.0% of patients in Group A and 42.1% of those in Group B. Preoperative MRSA bacteriuria was the only risk factor for SSI in both groups. The incidences of SSI in patients who had such bacteriuria were 45.4% in Group A and 50.0% in Group B. Modification of perioperative management for the surgical wound was partly responsible for the reduction of the incidence of SSI. In conclusion, MRSA is still the main isolated pathogen of SSI after radical cystectomy and this clinical problem remains a challenge to urologists. Effective countermeasures are needed for MRSA bacteriuria involved in the development of SSI.

In breast and colon cancers, transforming growth factor (TGF)-beta signaling initially has an antineoplastic effect, inhibiting tumor growth, but eventually exerts a proneoplastic effect, increasing motility and cancer spread. In prostate cancer, studies using human samples have correlated the loss of the TGF-beta type II receptor (T beta R II) with higher tumor grade. To determine the effect of an inhibited TGF-beta pathway on prostate cancer, we bred transgenic mice expressing the tumorigenic SV40 large T antigen in the prostate with transgenic mice expressing a dominant negative T beta R II mutant (DN II R) in the prostate. Transgene(s) and TGF-beta 1 expression were identified in the prostate and decreased protein levels of plasminogen activator inhibitor type I, as a marker for TGF-beta signaling, correlated with expression of the DN II R. Although the sizes of the neoplastic prostates were not enlarged, increased amounts of metastasis were observed in mice expressing both transgenes compared to age-matched control mice expressing only the large T antigen transgene. Our study demonstrates for the first time that a disruption of TGF-beta signaling in prostate cancer plays a causal role in promoting tumor metastasis.