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

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

[Undifferentiated Prostate Cancer Treated with Radiation Therapy].

We describe a 75-year-old man with undifferentiated prostate cancer that was treated with radiation therapy. He presented at a nearby general hospital with dysuria and pain upon micturition. He was diagnosed with undifferentiated prostate cancer by a needle biopsy and referred to our hospital for further examination and treatment. Enhanced computed tomography and magnetic resonance images showed prostate cancer and right obturator lymph node metastasis measuring 2.5 cm. Cystoscopy and colonoscopy revealed direct invasion of the urinary bladder and rectum. We constructed a vesical fistula and an artificial anus, and then treated the primary tumor and lymph node metastasis with radiation. Undifferentiated prostate cancer is extremely rare and to our knowledge only a few cases have been reported. We suggest that radiation might be effective for treating undifferentiated prostate cancer with or without local invasion and/or metastasis along with total body control.

Comparison between intravesical and oral administration of 5-aminolevulinic acid in the clinical benefit of photodynamic diagnosis for nonmuscle invasive bladder cancer.

BACKGROUND: This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5-aminolevulinic acid (ALA) (ALA-PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA-PDD (PDD-TURBT) for nonmuscle invasive bladder cancer. METHODS: Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA-induced fluorescence with the pathological result. PDD-TURBT was performed in 99 completely resectable cases corresponding to 210 ALA-PDD cases. To evaluate the abilities of PDD-TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT. RESULTS: The diagnostic accuracy and capability of ALA-PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA-PDD. The recurrence-free survival rate in the cases that underwent PDD-TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD-TURBT (hazard ratio, 0.578; P = .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence-free survival. All procedures were well tolerated by all patients without any severe adverse events. CONCLUSIONS: This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA-PDD and PDD-TURBT are remarkably helpful in detection and intraoperative navigation programs.

Pseudosarcomatous proliferation of cx43- and kit-expressing interstitial cell in the urinary bladder.

The authors report a case showing proliferation of KIT- and connexin 43-expressing mesenchymal cells of the urinary bladder. A 75-year-old woman had an ulcerated endophytic mass (size, approximately 2 × 2 cm) in the left posterolateral wall. She underwent transurethral resection and subsequent partial cystectomy. The suburothelial mass extended to the muscularis propria. The histopathological analysis revealed spindle-shaped mesenchymal cells that were loosely arranged with myxoid stroma and showed a focal compact fascicular arrangement. In the immunohistochemical analysis, these spindle cells were stained with specific antibodies to KIT and connexin 43. The patient is currently free of disease at 5 years after operation. The proliferating spindle cells in the present case might represent a phenotype of interstitial cells of the lamina propria.

[Clinical experience with transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD)].

PURPOSE: To report our clinical experience regarding transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD) with intravesical instillations of 5-aminolevulinic acid (ALA) and to assess the usefulness of the therapeutic method. MATERIALS AND METHODS: TUR-Bt guided by PDD was performed in 57 patients of which 47 were men and 10 women with a median age of 74.3 years (range 45-90), 36 were primary cases and 21 were recurrent cases with non-muscle invasive bladder cancer. Two to two and half hours prior to endoscopy 1.5 g ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K.K.) was used. The tumorous lesions under white light guidance and the lesion with fluorescent excitation under blue (fluorescence) light guidance were taken by cold cup as a biopsy and also resected sequentially. To evaluate the accuracy of PDD, the levels in images of the ALA-induced fluorescence were compared with the pathological results. To evaluate the availability of TUR-Bt guided by PDD, survival Analysis regarding vesical recurrence was retrospectively examined compared to the cases underwent conventional TUR-Bt under white light guidance. Moreover, in these cases, multivariate analysis using Cox proportional-hazards model was performed to detect the clinico-pathological factor independently contribute to improving prognosis. (Results) In the 301 specimens obtained from 57 patients, the sensitivity and specificity of PDD were 92.5% and 60.1%, whereas the sensitivity and specificity of conventional endoscopic examination under white light guidance were 81.6% and 79.5%, respectively. Median follow-up period was 19.1 (range 8.6-49.9) months in 57 patients underwent TUR-Bt guided by PDD. Eight of 57 patients recurred and recurrence-free survival rate was 88.2 +/- 0.1% (at 12 months) and 76.2 +/- 0.1% (24-48 months). Median follow-up period was 49.9 (5.0-145.0) months in 149 patients underwent conventional TUR-Bt. Ninety-nine of 149 patients recurred and recurrence-free survival rate was 60.3 +/- 0.0% (12 months) and 31.6 +/- 0.0% (24-48 months). There was statistical significance in recurrence-free survival rate between these 2 therapeutic groups (p < 0.001). Moreover, multivariate analysis revealed the independent factor contribute to improving prognosis was only TUR-Bt guided by PDD (hazard ratio 0.279, p = 0.001). CONCLUSION: It was suggested that TUR-Bt guided by PDD might reduce the risk of vesical recurrence in the early stage after operation of non-muscle invasive bladder cancer.

Molecular detection of von Hippel-Lindau gene mutations in urine and lymph node samples in patients with renal cell carcinoma: potential biomarkers for early diagnosis and postoperative metastatic status.

PURPOSE: Organ confined renal cell carcinoma can be cured in the majority of patients, whereas more extensive lesions have a poor prognosis. Therefore, the development of a useful biomarker for early diagnosis as well as postoperative metastatic status would contribute to the appropriate therapy for renal cell carcinoma. To diagnose renal cell carcinoma preoperatively we developed a novel urinary test and detected occult lymph node micrometastasis using a molecular approach. MATERIALS AND METHODS: Urine samples were obtained preoperatively from 27 patients with renal cell carcinoma and von Hippel-Lindau (VHL) gene mutations in the tumors, and were analyzed for VHL gene mutations using a nested single strand conformational polymorphism analysis. Lymph nodes without evidence of histological metastasis were obtained from 15 patients with renal cell carcinoma and VHL gene mutations, and analyzed for VHL gene mutations using mutation specific nested reverse transcription polymerase chain reaction method. RESULTS: In urine samples 5 of 27 VHL gene mutations (18.5%) were found and each mutation pattern was the same as that detected in each renal cell carcinoma. One lymph node micrometastasis was found. CONCLUSIONS: These data indicate the presence of detectable levels of tumor derived DNA in the urine of patients with renal cell carcinoma and suggest that nested single strand conformational polymorphism analysis of VHL gene of urine samples provides a possible tool for the early detection of renal cell carcinoma. Furthermore, mutation specific nested reverse transcription polymerase chain reaction is useful to detect occult lymph node micrometastasis and may predict patients at risk for local recurrence. These 2 combined approaches using VHL gene mutations may contribute to the total therapy for and prognosis of renal cell carcinoma.

Effects of von Hippel-Lindau gene mutation and methylation status on expression of transmembrane carbonic anhydrases in renal cell carcinoma.

PURPOSE: Our primary goal was to determine whether increased expression of the transmembrane carbonic anhydrase (CA) isozymes in renal cell carcinoma (RCC) is regulated by the von Hippel-Lindau (VHL) gene. METHODS: We studied mRNA expression of all three transmembrane CAs - CA IX, XII, and XIV - in 17 RCC cell lines, transformants of the wild-type VHL gene, and normal kidney tissue cultures, and then compared them with the mutation status in the VHL gene. RESULTS: Northern blot analysis showed no detectable signal for CA XIV mRNA expression in normal and cancer cells. CA XII mRNA was ubiquitously expressed except in two cell lines. Although CA XII expression levels tended to be lower in RCC cell lines without the VHL mutation and in transformants of the wild-type VHL gene, the results were not conclusive. Significant expression of CA IX mRNA was seen in eight of 17 RCC cell lines. Among five cell lines which had no VHL mutation, four lines showed no detectable signal and one cell line showed a low amount of CA IX mRNA expression. In patients with RCC, VHL mutations and significant CA IX expression were seen in established tumor cell lines but not in primary tissue cultures from normal counterparts. Further study of methylation status showed that the 5' region in the CA9 gene was hypomethylated in all CA IX-positive cell lines and hypermethylated in all CA IX-negative cell lines. Especially, methylation status at -74 and -6 CpG sites perfectly correlated with CA IX expression. CONCLUSIONS: These findings indicate that VHL suppresses CA IX expression but has no conclusive effect on CA XII and XIV expressions in RCC. CA IX expression is also driven by the methylation status of the CA9 gene.