Objectives
To detect microorganisms responsible for male acute urethritis and to define the microbiology of non‐gonococcal urethritis.
Methods
The present study comprised 424 men with symptoms and ...signs compatible with acute urethritis. Their urethral swabs and first‐voided urine underwent detection of the microorganisms. Demographic characteristics and clinical features of Mycoplasma genitalium‐, Ureaplasma urealyticum‐, Haemophilus influenza‐, adenovirus‐ or Herpes simplex virus‐positive monomicrobial non‐gonococcal urethritis, or all‐examined microorganism‐negative urethritis in heterosexual men were compared with urethritis positive only for Chlamydia trachomatis.
Results
Neisseria gonorrhoeae was detected in 127 men (30.0%). In 297 men with non‐gonococcal urethritis, C. trachomatis was detected in 143 (48.1%). In 154 men with non‐chlamydial non‐gonococcal urethritis, M. genitalium (22.7%), M. hominis (5.8%), Ureaplasma parvum (9.1%), U. urealyticum (19.5%), H. influenzae (14.3%), Neisseria meningitidis (3.9%), Trichomonas vaginalis (1.3%), human adenovirus (16.2%), and Herpes simplex virus types 1 (7.1%) and 2 (2.6%) were detected. Although some features of monomicrobial non‐chlamydial non‐gonococcal urethritis or all‐examined microorganism‐negative urethritis were significantly different from those of monomicrobial chlamydial non‐gonococcal urethritis, most features were superimposed.
Conclusions
Predicting causative microorganisms in men with non‐gonococcal urethritis based on demographic and clinical features is difficult. However, the present study provides useful information to better understand the microbiological diversity in non‐gonococcal urethritis, and to manage patients with non‐gonococcal urethritis appropriately.
Unlike urinary tract infection (UTI), asymptomatic bacteriuria (ABU) should not be treated, with some exceptions such as pregnant women and patients who will undergo traumatic urologic interventions. ...However, there has been no clinically available marker for their differential diagnosis. Exosomes or small extracellular vesicles carry proteins contained in cells from which they are derived, thus having the potential as a biomarker of several diseases. On the basis of the hypothesis that the molecular signature of exosomes in urine may differ between UTI and ABU patients, we examined if urinary exosomes could serve as a marker for their differential diagnosis. Exosomes were isolated by ultracentrifugation or affinity‐based method from cell culture medium of monocytic THP‐1 and uroepithelial SV‐HUC‐1 cells and human urine. Protein expression was examined by Western blot analysis, ELISA, and CLEIA. The results showed that the levels of intracellular signalling molecules Akt and ERK and transcription factor NF‐κB increased in exosomes isolated from THP‐1 and SV‐HUC‐1 cells cocultured with Escherichia coli and/or treated with lipopolysaccharide. In urinary exosomes of UTI patients, Akt significantly diminished, and an exosomal marker CD9 showed a trend to decrease after treatment with antimicrobial agents. More importantly, Akt and CD9 levels in urinary exosomes were higher in UTI patients than in ABU patients, which was also observed after correction by urine creatinine. Collectively, these results suggest that Akt and CD9 in urinary exosomes could be useful markers for differential diagnosis of UTI and ABU.
Radical cystectomy remains the gold standard for treatment of muscle‐invasive bladder cancer. Robot‐assisted radical cystectomy has technical advantages over laparoscopic radical cystectomy and has ...emerged as an alternative to open radical cystectomy. Despite the advancements in robotic surgery, experience with total intracorporeal reconstruction of urinary diversion remains limited. Most surgeons have carried out the hybrid approach of robot‐assisted radical cystectomy and extracorporeal reconstruction of urinary diversion, as intracorporeal reconstruction of urinary diversion remains technically challenging. However, intracorporeal reconstruction of urinary diversion might potentially proffer additional benefits, such as decreased fluid loss, reduction in estimated blood loss and a quicker return of bowel function. The adoption of intracorporeal ileal neobladder reconstruction has hitherto been limited to high‐volume academic institutions. In the present review, we compare the totally intracorporeal robot‐assisted radical cystectomy approach with open radical cystectomy and robot‐assisted radical cystectomy + extracorporeal reconstruction of urinary diversion in muscle‐invasive bladder cancer patients.
Cabazitaxel (CBZ) is now widely used for prostate cancer (PC) patients resistant to docetaxel (DOC), however, most patients eventually acquire resistance. It will, therefore, be of great benefit to ...discover novel therapeutic target for the resistance. We aimed to identify candidate therapeutic targets for CBZ-resistance by proteomic analysis of extracellular vesicles (EVs) isolated from serum of DOC-resistant PC patients who later developed CBZ-resistance as well as those harvested from culture medium of DOC- and CBZ-resistant PC cell lines.
Using T-cell immunoglobulin domain and mucin domain-containing protein 4 (Tim4) conjugated to magnetic beads, EVs were purified from serum of PC patients with DOC-resistance that was collected before and after acquiring CBZ-resistance and conditioned medium of DOC-resistant (22Rv1DR) and CBZ-resistant (22Rv1CR) PC cell lines. Protein analysis of EVs was performed by nanoLC-MS/MS, followed by a comparative analysis of protein expression and network analysis. The cytotoxic effect of a phosphatidylinositol-3-kinase (PI3K) inhibitor, ZSTK474, was evaluated by WST-1 assay. The expression and phosphorylation of PI3K and PTEN were examined by western blot analysis.
Among differentially regulated proteins, 77 and 61 proteins were significantly increased in EVs from CBZ-resistant PC cell line and patients, respectively. A comparison between the two datasets revealed that six proteins, fructose-bisphosphate aldolase, cytosolic nonspecific dipeptidase, CD63, CD151, myosin light chain 9, and peroxiredoxin-6 were elevated in EVs from both cell line and patients. Network analysis of the increased EV proteins identified pathways associated with CBZ-resistance including PI3K signaling pathway. ZSTK474 significantly inhibited growth of 22Rv1CR cells and improved their sensitivity to CBZ. In 22Rv1CR cells, PI3K was activated and PTEN that inhibits PI3K was deactivated.
Proteomic analysis of serum EVs was successfully accomplished by using Tim-4 as a tool to isolate highly purified EVs. Our results suggest that the combination use of CBZ and PI3K inhibitor could be a promising treatment option for CBZ-resistant PC patients.
Mycoplasma genitalium was detected in 21 (14.1%) of 149 vaginal swab samples and in 1 (0.7%) of 149 throat washing samples from female sex workers during 2013-2014 in Japan. Prevalences of M. ...genitalium with macrolide resistance-associated 23S rRNA mutations and fluoroquinolone resistance-associated parC alterations were 47.1% and 36.8%, respectively.
Background
This study aimed to evaluate the association between clinical covariates or the prescribed radiation dose for the prostate and rectal hemorrhage in patients with prostate cancer (PCa) who ...received iodine-125 low-dose-rate brachytherapy (LDR-BT group) or the combination of LDR-BT and external beam radiation therapy (CMT group).
Methods and materials
In this retrospective study, we reviewed the clinical records of 298 consecutive PCa patients with clinical stage T1c/T2 who underwent LDR-BT between August 2004 and August 2016 at a single institution. The prescribed minimum peripheral doses were 145 Gy for the LDR-BT group and 104 Gy for the CMT group. The dosimetric parameters analyzed were minimal dose received by 90% of the prostate gland, biologically effective dose, and rectal volume receiving 100% (RV100) or 150% of the prescribed dose. The endpoint of this study was the onset of any-grade clinical rectal hemorrhage after treatment.
Results
The median follow-up period was 6.8 years. The 5-year overall survival rate was found to be 98.3%, and two patients (0.7%) reported biochemical recurrence during follow-up period. A total of 33 patients (11%) experienced rectal hemorrhage. However, ≥ grade 2 rectal hemorrhage occurred in eight patients (2.7%). On multivariate analysis, CMT, RV100 ≥ 0.66 mL, and hemorrhoids before treatment were identified as predictors of rectal hemorrhage after radiation therapy.
Conclusions
Maximal reduction of the rectal dose seems very important to prevent serious rectal hemorrhage. In addition, we should consider the risk of rectal toxicities in patients with abnormalities in the rectal mucosa, especially hemorrhoids.
Background
Apalutamide, a nonsteroidal potent androgen receptor antagonist, was safe and effective in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic-CRPC ...(mCRPC) in global studies. In this phase 1 study, safety, pharmacokinetics (PK), and efficacy of apalutamide were evaluated in Japanese patients with mCRPC.
Methods
In this open-label, multi-center study, patients received apalutamide 240 mg (once-daily, orally) for first 1 week (PK week) during which PK parameters were assessed. 1 week later (Cycle 1 Day1), after reassessing safety, continuous daily dosing (4 weeks/cycle; once-daily orally) was initiated. Endpoints evaluated were: safety, tolerability, PK and antitumour efficacy of apalutamide. Dose-limiting toxicities (DLTs) were evaluated during PK week and Cycle 1.
Results
All six patients received apalutamide. The most common treatment-emergent adverse events (TEAEs) were abdominal discomfort, nasopharyngitis, dysgeusia, rash, and hot flush 2/6 patients (33.3%) each. No death or DLTs were reported. Grade 3 TEAEs were spinal-cord compression and renal disorder (1/6 patient each). In continuous daily dosing period, PK steady-state of apalutamide was reached approximately by week 4. A significant accumulation of apalutamide was observed (mean accumulation index 3.55), based on AUC
0–24
. Median (range) serum prostate-specific antigen level decreased from 54.42 (8.92–310.11) ng/mL at baseline to 11.70 (0.37–47.74) ng/mL at week 12 with ≥ 50% reduction in 4/6 (66.7%) patients and 90% reduction in 2/6 (33.3%) patients.
Conclusion
Apalutamide had manageable safety profile, without any DLT or any new safety signals, and favourable efficacy in Japanese mCRPC patients. Thus, it was ascertained to be an adequate dosage regimen in Japanese mCRPC patients.
Trial registration
ClinicalTrials.gov identifier: NCT02162836.
Objectives: Acute epididymitis is often associated with urethritis. Mycoplasma genitalium and Ureaplasma urealyticum have been considered as pathogens of urethritis. The aim of the present study was ...to determine the prevalence of these microorganisms in men with acute epididymitis.
Method: A total of 56 men younger than 40 years‐of‐age with acute epididymitis were enrolled in the present study between January 2006 and June 2010. First‐void urine specimens were subjected to culture of aerobic bacterial species, and examined for the presence of Chlamydia trachomatis, M. genitalium, M. hominis, U. parvum and U. urealyticum by polymerase chain reaction‐based assays. Urethral swabs were cultured for Neisseria gonorrhoeae.
Results: The number and percentage of patients positive for each microorganism were as follows: Gram‐negative bacilli, 2% and 3.6%; Gram‐positive cocci, 23% and 41.1%; N. gonorrhoeae, 3% and 5.4%; C. trachomatis, 28% and 50.0%; M. genitalium, 5% and 8.9%; M. hominis, 6% and 10.7%; U. parvum, 6% and 10.7%; and U. urealyticum, 5% and 8.9%. Among 25 men with non‐chlamydial non‐gonococcal epididymitis, who were negative for Gram‐negative bacilli, M. genitalium or U. urealyticum was detected in one man each (4.0%), and M. hominis and/or U. parvum was detected in five (20.0%).
Conclusion: In men younger than 40 years‐of‐age with acute epididymitis, C. trachomatis is a major pathogen. The prevalence of genital mycoplasmas and ureaplasmas are lower, and the role of genital mycoplasmas and ureaplasmas in the development of acute epididymitis remains to be determined.
Background
The risk of malignant neoplasms increases in kidney transplantation (KT) recipients (KTRs). However, Japanese registry studies have not been reported since 2000.
Methods
We retrospectively ...reviewed the medical records of 346 patients who underwent KT at Gifu University Hospital, Japan since 2000. Patients were divided into two groups based on whether they developed malignancy after KT or not. The incidence, type of malignancy, risk factors, and prognosis for malignancy were examined.
Results
In this study, 22 de novo malignant neoplasms were identified in 20 KTRs (7.3%), with a median follow-up period of 8.2 years. Cumulative incidence of any malignant neoplasms was 1.1% within 1 year and 4.4% within 5 years. The 5-year overall survival (OS) rates were 71.8% in KTRs with malignant neoplasms and 98.6% in KTRs without malignant neoplasms. Uni- and multivariate analysis revealed that age at KT and acute rejection (AR) episode were significant predictors for incidence of malignancy.
Conclusions
The development of malignant neoplasms was associated with poor OS and graft survival. We consider that appropriate screening and investigation of symptoms are important for KTRs, particularly for older KTRs at transplantation and those with AR episode.
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