Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

Infection risk reduction with povidone-iodine rectal disinfection prior to transrectal prostate biopsy: an updated systematic review and meta-analysis.

BACKGROUND: To prevent infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-PB), some studies have investigated the efficacy of rectal disinfection using povidone-iodine (PI) and antibiotic prophylaxis (AP). OBJECTIVE: To summarize available data and compare the efficacy of rectal disinfection using PI with non-PI methods prior to TRUS-PB. EVIDENCE ACQUISITION: Three databases were queried through November 2023 for randomized controlled trials (RCTs) analyzing patients who underwent TRUS-PB. We compared the effectiveness of rectal disinfection between PI groups and non-PI groups with or without AP. The primary outcomes of interest were the rates of overall infectious complications, fever, and sepsis. Subgroups analyses were conducted to assess the differential outcomes in patients using fluoroquinolone groups compared to those using other antibiotics groups. EVIDENCE SYNTHESIS: We included ten RCTs in the meta-analyses. The overall rates of infectious complications were significantly lower when rectal disinfection with PI was performed (RR 0.56, 95% CI 0.42-0.74, p < 0.001). Compared to AP monotherapy, the combination of AP and PI was associated with significantly lower risk of infectious complications (RR 0.54, 95% CI 0.40-0.73, p < 0.001) and fever (RR 0.47, 95% CI 0.30-0.75, p = 0.001), but not with sepsis (RR 0.49, 95% CI 0.23-1.04, p = 0.06). The use of fluoroquinolone antibiotics was associated with a lower risk of infectious complications and fever compared to non-FQ antibiotics. CONCLUSION: Rectal disinfection with PI significantly reduces the rates of infectious complications and fever in patients undergoing TRUS-PB. However, this approach does not show a significant impact on reducing the rate of sepsis following the procedure.

Differential effect of surgical technique on intravesical recurrence after radical nephroureterectomy in patients with upper tract urothelial cancer: a systematic review and Meta-analysis.

CONTEXT: Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC. OBJECTIVE: To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients. EVIDENCE ACQUISITION: Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU. EVIDENCE SYNTHESIS: Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44-0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06-1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51-0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15-2.34, p = 0.006, respectively). CONCLUSIONS: EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy.

Homology of Escherichia coli isolated from urine and vagina and their antimicrobial susceptibility in postmenopausal women with recurrent cystitis.

Uropathogenic Escherichia coli (UPEC) is a typical cystitis-causing organism that can migrate from the vagina to the bladder and cause recurrent cystitis (RC). Few reports have compared the characteristics of urinary and vaginal UPEC in patients with RC. We carried out molecular biological analyses of Escherichia coli (E. coli) strains and their antimicrobial susceptibility to assess the association between urinary and vaginally UPEC. We included E. coli isolated from urinary and vaginal samples at the onset of cystitis in postmenopausal women with RC between 2014 and 2019 in our hospital. Pulsed-field gel electrophoresis (PFGE) was performed using a restriction enzyme (Xba I). These sequences were compared with 17 antimicrobial susceptibilities determined by a micro-liquid dilution method. Multilocus sequence typing (MLST) and classification of extended-spectrum ß-lactamase (ESBL) genotypes by multiplex polymerase chain reaction (PCR) were performed on ESBL-producing E. coli. We analyzed 14 specimens (each seven urine and vaginal) from seven patients in total. On PFGE, the similarity of urinary and vaginal E. coli per patient ranged from 89.5 to 100 %, including four patients with 100 % matches. MLST demonstrated that 29 % (4/14 specimens) were strain sequence type 131. Two specimens contained ESBL-producing strains and identified the CTX-M-27 genotype for each specimen. For each patient, antimicrobial susceptibilities between urinary and vaginal E. coli were mostly identical. Thus, urinary- and vaginally-derived E. coli were identical in postmenopausal women with RC. Management targeting both urinary and vaginal UPEC is essential for RC, indicating the importance of a vagina-targeted approach.

Fluoroquinolone resistance and clinical characteristics of acute bacterial prostatitis in Japan: A multicenter study by the Japanese research group for urinary tract infection.

OBJECTIVE: This multicenter study aimed to analyze the risk factors for fluoroquinolone (FQ) resistance and to clarify the clinical characteristics of acute bacterial prostatitis (ABP) in Japan. METHODS: A total of 124 patients clinically diagnosed with ABP at 13 medical institutions participating in the Japanese Research Group for Urinary Tract Infection between January and December 2017 were retrospectively reviewed. RESULTS: Of the 124 patients included in this study, 37 were outpatients, and 87 were inpatients. The main underlying medical conditions before the onset of ABP were severe dysuria, urinary retention, transurethral manipulation, indwelling urinary catheter, and transrectal prostate biopsy (TRBx). The main symptoms were fever (≥37.5 °C), prostate tenderness, dysuria, micturition pain, urinary retention, and macrohematuria. Bacteremia was observed in 14 patients. Prostatic abscess was observed in three patients. Escherichia coli was the predominant organism, accounting for 48 % (51/106). FQ-resistant E. coli was detected in 33 % (17/51), and extended-spectrum beta-lactamase-producing E. coli in 12 % (6/51). TRBx (odds ratio [OR] = 48.60, 95 % confidence interval [CI]: 5.49-430.00, p < 0.001) and inpatient status (OR = 29.00, 95 % CI: 1.95-430.00, p = 0.014) were risk factors for the detection of FQ-resistant bacteria. CONCLUSIONS: The detection rate of FQ-resistant bacteria was significantly higher with TRBx ABP and inpatient status. These findings have important implications for the management of ABP and antimicrobial treatment, especially for TRBx ABP, which should be considered a separate category.

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.

Third nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2020 and 2021: Antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

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 ß-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.

Reproductive organ involvement in women undergoing radical cystectomy for urothelial bladder cancer: a nationwide multicenter study.

BACKGROUND: Radical cystectomy in women generally includes the removal of the uterus, ovaries, and anterior vaginal wall, but the criteria for reproductive organ sparing are not clear. METHODS: A total of 2674 patients with bladder cancer were retrospectively reviewed, having undergone cystectomy at this nationwide multicenter from January 2013 to December 2019. We evaluated the incidence of malignancy in reproductive organs in a cohort of 417 women and analyzed the clinicopathological features of reproductive organ involvement. Recurrence-free survival and overall survival were reported using Kaplan-Meier survival curves. RESULTS: Median follow-up was 36.9 months. Of the 417 patients with urothelial carcinoma of the bladder, 325 underwent hysterectomy, and 92 had a spared uterus and anterior wall of the vagina. Twenty-nine (8.9%) patients exhibited reproductive organ involvement; this consisted of 22 (6.8%) uteri, 16 (4.9%) vaginas, and two (0.6%) ovaries. Incidental primary reproductive malignancies were found in only two (0.6%) patients. Recurrence-free survival and overall survival were significantly shorter in patients with reproductive organ involvement than in those without. Patients with reproductive organ involvement were more likely to have tumors with ≥ cT3 or sub-localization at the posterior/trigone/bladder neck. CONCLUSIONS: The risk of reproductive organ involvement cannot be ignored in women undergoing radical cystectomy for urothelial carcinoma of the bladder, therefore, the eligibility criteria for reproductive organ preservation should be considered carefully.

Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma.

UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC.

The third nationwide surveillance of antimicrobial susceptibility against Neisseria gonorrhoeae from male urethritis in Japan, 2016-2017.

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 ß-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.

Substrate stiffness modulates endothelial cell function via the YAP-Dll4-Notch1 pathway.

Endothelial cells adapt their functions as a consequence of sensing extracellular substrate stiffness; these alterations allow them to maintain their vascular structure and function. Substrate stiffness-mediated yes-associated protein 1 (YAP) activation plays an important role in mechano-transduction and pro-angiogenic phenotype of endothelial cells, and Delta-like ligand 4 (Dll4)-Notch1 signaling is closely related to angiogenesis; however, the impact of substrate stiffness-mediated interrelation of these pathways on endothelial cell functions remains elusive. We confirmed that endothelial cells on softer substrates not only elongate cellular aspects but also attenuate YAP activation compared to cells on stiffer substrates. Endothelial cells on softer substrates also upregulate the vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 mRNA expression that is enhanced by VEGF stimulation. We determined that endothelial cells on softer substrates increased Dll4 expression, but not Notch1 expression, via YAP signaling. Moreover, endothelial cells on soft substrates induced not only VEGFRs upregulation but also suppression of pro-inflammatory interleukin-6 and plasminogen activator inhibitor-1 mRNA expression and the facilitation of anti-coagulant thrombomodulin and pro-coagulant tissue factor mRNA expression. Our results suggest that endothelial cells activate the YAP-Dll4-Notch signaling pathway in response to substrate stiffness and dictate cellular function.

Distribution of the positive UPOINT domain in patients with chronic prostatitis or chronic pelvic pain syndrome: A multicenter observational study.

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).

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.

Japanese linguistic validation of the ureteral stent symptom questionnaire.

OBJECTIVE: We validated the Japanese version of the ureteral stent symptom questionnaire in patients with an indwelling ureteric stent. METHODS: The English version of the ureteral stent symptom questionnaire was translated into Japanese using a multistep process by three urologists and two independent translators. A total of 70 patients with indwelling ureteral stents completed the Japanese ureteral stent symptom questionnaire, as well as validated instruments, namely, the International Prostate Symptom Score or Overactive Bladder Symptom Score and the EuroQoL 5-dimension questionnaires. Patients completed questionnaires at 2 weeks after stent insertion and 4 weeks after stent removal. The second group included 87 healthy individuals who agreed to complete the questionnaires. The reliability of the Japanese version was evaluated for internal consistency using Cronbach's α test. Psychometric properties of the questionnaire were analyzed, and included convergent validity, sensitivity to change and discriminant validity. RESULTS: A total of 70 cases and 87 controls were suitable for the analysis. A comparison of patients with ureteric stents and healthy individuals was carried out, and the convergent validity determined by the correlation between other instruments and the corresponding ureteral stent symptoms questionnaire domains was satisfactory (P < 0.05). Internal consistencies (Cronbach's α coefficients 0.73-0.80) were satisfactory, except for the sexual matters domain. Test-retest reliability was good, except for the sexual matters domain (Spearman's coefficient 0.71-0.93). CONCLUSIONS: The Japanese version of the ureteral stent symptom questionnaire proved to be a reliable and robust instrument for the evaluation of ureteral stent-associated morbidity for both men and women.

Post-prostate biopsy acute bacterial prostatitis and screening cultures using selective media: An overview.

The development of several culture media and the availability to isolate and treat pathogens prior to a surgical procedure give us the ability to minimize treatment-related complications, and ultimately results in better outcomes for patients and avoidance of unwanted post-procedure inpatient admissions. In the last decade, an increasing incidence of multidrug-resistant Escherichia coli, especially extended-spectrum beta-lactamase-producing E. coli and fluoroquinolone-resistant pathogens, has been reported. These resistant species frequently colonize the rectal flora and gain access to the systemic circulation via the rectal plexus following a prostate biopsy. The bacteria can eventually lead to life-threatening complications, which is especially important in high-risk patients with multiple co-morbidities. Previously published studies have focused on the isolation of these pathogens with selective media before an invasive procedure and the potential benefits of incorporating the use of selective media as a mandatory pre-operative step. This preventive measure will allow us to offer a tailored prophylactic treatment that benefits patients and reduces the economic burden for the hospital.

Gut microbiota composition associated with hepatic fibrosis in non-obese patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Gut microbiota composition is associated with the pathogenesis of non-alcoholic fatty liver disease. However, the association between gut microbiota composition and non-alcoholic fatty liver disease in non-obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non-obese and obese patients with non-alcoholic fatty liver disease. METHODS: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short-chain fatty acid levels in fecal samples from 51 non-obese patients with non-alcoholic fatty liver disease (body mass index <25 kg/m2 ) and 51 obese patients with non-alcoholic fatty liver disease (body mass index ≥30 kg/m2 ) who underwent pathological examination and 87 controls at five hospitals in Japan. RESULTS: Although no significant differences between the non-obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non-obese patients with non-alcoholic fatty liver disease compared with those in obese patients with non-alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non-obese patients with non-alcoholic fatty liver disease. CONCLUSIONS: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non-alcoholic fatty liver disease in non-obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917).

Long-term ureteroscopic management of upper tract urothelial carcinoma: 28-year single-centre experience.

BACKGROUND: Long-term survival outcomes of patients who undergo endoscopic management of non-invasive upper tract urothelial carcinoma remain uncertain. The longest mean follow-up period in previous studies was 6.1 years. This study reports the long-term outcomes of patients with upper tract urothelial carcinoma who underwent ureteroscopic ablation at a single institution over a 28-year period. METHODS: We identified all patients who underwent ureteroscopic management of upper tract urothelial carcinoma as their primary treatment at our institution between January 1991 and April 2011. Survival outcomes, including overall survival, cancer-specific survival, upper-tract recurrence-free survival and renal unit survival, were estimated using Kaplan-Meier methodology. RESULTS: A total of 15 patients underwent endoscopic management, with a mean age at diagnosis of 66 years. All patients underwent ureteroscopy, and biopsy-confirmed pathology was obtained. Median (range; mean) follow-up was 11.7 (2.3-20.9, 11.9) years. Upper tract recurrence occurred in 87% (n = 13) of patients. Twenty percent (n = 3) of patients proceeded to nephroureterectomy. The estimated cancer-specific survival rate was 93% at 5, 10, 15 and 20 years. Estimated overall survival rates were 86, 80, 54 and 20% at 5, 10, 15 and 20 years. Only one patient experienced cancer-specific mortality. The estimated mean and median overall survival times were 14.5 and 16.6 years, respectively. The estimated mean cancer-specific survival time was not reached. CONCLUSIONS: Although upper tract recurrence is common, endoscopic management of non-invasive upper tract urothelial carcinoma provides a 90% cancer-specific survival rate at 20 years in selected patients.

Photodynamic diagnostic ureteroscopy using the VISERA ELITE video system for diagnosis of upper-urinary tract urothelial carcinoma: a prospective cohort pilot study.

BACKGROUND: The advantages of photodynamic diagnostic technology using 5-aminolevulinic acid (ALA-PDD) have been established. The aim of this prospective cohort study was to evaluate the usefulness of ALA-PDD to diagnose upper tract urothelial carcinoma (UT-UC) using the Olympus VISERA ELITE video system. METHODS: We carried out a prospective, interventional, non-randomized, non-contrast and open label cohort pilot study that involved patients who underwent ureterorenoscopy (URS) to detect UT-UC. 5-aminolevulinic acid hydrochloride was orally administered before URS. The observational results and pathological diagnosis with ALA-PDD and traditional white light methods were compared, and the proportion of positive subjects and specimens were calculated. RESULTS: A total of 20 patients were enrolled and one patient who had multiple bladder tumors did not undergo URS. Fifteen of 19 patients were pathologically diagnosed with UT-UC and of these 11 (73.3%) were ALA-PDD positive. Fourteen of 19 patients were ALA-PDD positive and of these 11 were pathologically diagnosed with UC. For the 92 biopsy specimens that were malignant or benign, the sensitivity for both traditional white light observation and ALA-PDD was the same at 62.5%, whereas the specificities were 73.1% and 67.3%, respectively. Of the 38 specimens that were randomly biopsied without any abnormality under examination by both white light and ALA-PDD, 11 specimens (28.9%) from 5 patients were diagnosed with high grade UC. In contrast, four specimens from 4 patients, which were negative in traditional white light observation but positive in ALA-PDD, were diagnosed with carcinoma in situ (CIS). CONCLUSIONS: Our results suggest that ALA-PDD using VISERA ELITE is not sufficiently applicable for UT-UC. Nevertheless, it might be better particularly for CIS than white light and superior results would be obtained using VISERA ELITE II video system. TRIAL REGISTRATION: The present clinical study was approved by the Okayama University Institutional Review Board prior to study initiation (Application no.: RIN 1803-002) and was registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (Accession no.: UMIN000031205).

UAA-AAUS guideline for M. genitalium and non-chlamydial non-gonococcal urethritis.

Non-chlamydial non-gonococcal urethritis (NCNGU) is defined as urethritis with neither Neisseria gonorrhoeae nor Chlamydia trachomatis. Possible causative agents of NCNGU include Mycoplasma genitalium, Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, Trichomonas vaginalis, and so on. Among these microorganisms, the pathogenicity of M. genitalium and T. vaginalis to the male urethra has been confirmed so far. The Asian Association of Urinary Tract Infection and Sexually Transmitted Infection (AAUS) belonging to the Urological Association of Asia (UAA) had developed the guidelines regarding NCNGU and the present guidelines were updated from previous edition. Relevant references were meticulously reviewed again and latest studies were collected. In addition to the levels of evidence, the recommendation grades were defined using the modified GRADE methodology. Herein, we present the new edition of the UAA-AAUS guidelines for M. genitalium and non-chlamydial non-gonococcal urethritis.

Successful deceased donor kidney transplantation to a recipient with a history of COVID-19 treatment.

CASE PRESENTATION: A 49-year-old Asian male, who had undergone hemodialysis for >16 years, complained of a fever, dysgeusia and dysosmia, and was diagnosed with COVID-19 pneumonia based on severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (SARS-CoV-2 PCR) and computed tomography (CT). Treatment was started with oral favipiravir and ciclesonide inhalation. On the 10th day of treatment, the patient had a persistent high fever and a chest CT showed exacerbation of pneumonia, so dexamethasone was intravenously started. He was discharged after confirming two consecutive negative SARS-CoV-2 PCR tests. Three months after COVID-19 treatment, a SARS-CoV-2 PCR test was negative and he underwent a deceased donor kidney transplantation. Basiliximab induction with triple drug immunosuppression consisting of extended-release tacrolimus, mycophenolate mofetil and prednisolone, which is our regular immunosuppression protocol, was used. He was discharged on postoperative day 18 without the need for postoperative hemodialysis or any complications. The serum creatinine level was 1.72 mg/dL 95 days postoperatively and he had a favorable clinical course that was similar to deceased donor kidney recipients without a history of SARS-CoV-2 infection. CONCLUSION: We report the first case of a kidney transplantation after COVID-19 treatment in Japan and the fourth case globally. We would like to provide information about our successful case due to the anticipated increase in similar candidates in the near future.