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.

Profilin 1 overexpression in renal cell carcinoma.

OBJECTIVES: To gain information about overexpressed antigens in renal cell carcinoma (RCC) by using a chemical proteomics approach. METHODS: RCC cell line 769P was cultured and proteome analysis was subsequently carried out in the culture supernatants. By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tandem mass spectrometry (LC-MS/MS), proteins in the culture supernatants were searched. A MEDLINE search to define the functions of the identified proteins was carried out. RESULTS: Four differentially regulated proteins (profilin 1, amyloid beta A4 protein [APP], proprotein convertase subtilisin/kexin type 1 inhibitor [ProSAAS], galectin-3-binding protein [LGALS3BP]) were selected. These were not overexpressed in normal kidney tissue or reported in RCC. Their levels were measured through western blotting of normal kidney and RCC tissues. No differences were observed in the expression levels of APP, ProSAAS or LGALS3BP between RCC and normal kidney tissues. Profilin 1 was overexpressed in RCC tissue. On the basis of this observation, an immunohistochemical analysis of profilin 1 in normal kidney and RCC tissues was carried out. In normal tissues, tubules that were sources of RCC stained positive for profilin 1. In RCC tissue, in contrast, the stromal cells in the tumors stained positive. CONCLUSIONS: Profilin 1 can be a key element in the pathological processes of RCC, such as tumorigenesis and/or tumor growth. Thus, it has the potential to serve as a diagnostic or progression biomarker and therapeutic target in RCC.

[Case report: a patient with bladder sarcoma exclusively treated with transurethral resection with long-term follow-up].

Sarcoma is a rare malignant lesion in the urinary bladder and remains unknown of its natural history. We report a case of primary bladder sarcoma with long-term follow-up. A 35-year-old man suddenly presented with severely gross hematuria. Computer tomography was showed solitary lesion at the anterior wall of the urinary bladder without distant metastases. Transurethral resection of the bladder tumor (TURBT) was performed. Pathologic findings demonstrated sarcoma in the urinary bladder without remnant lesions. Immunohistochemical staining using conventional antibodies was not classified as the origin of this sarcoma. There have been no signs of recurrence during twenty years' follow-up after the treatment.

Single infusion of zoledronic acid to prevent androgen deprivation therapy-induced bone loss in men with hormone-naive prostate carcinoma.

BACKGROUND: Androgen-deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone-naive prostate carcinoma. METHODS: Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual-energy x-ray absorptiometry and urinary N-telopeptide (u-NTx) at 6 and 12 months. RESULTS: At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6 months, mean (+/-standard error) BMD of the posteroanterior lumbar spine decreased 4.6%+/-1.0% in control patients and increased 5.1%+/-1.2% in patients receiving zoledronic acid, a significant difference (P=.0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P=.0004), indicating that zoledronate preserved BMD. For u-NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P<.0001), but returned to pretreatment levels at 12 months in the zoledronate group. CONCLUSIONS: Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT-induced bone loss in men with hormone-naive prostate carcinoma.

Genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with Hypofractionated External beam radiotherapy for localized prostate cancer: an analysis to determine the correlation between dose-volume histogram parameters in HDR brachytherapy and severity of toxicity.

PURPOSE: To evaluate the severity of genitourinary (GU) toxicity in high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiotherapy (EBRT) for prostate cancer and to explore factors that might affect the severity of GU toxicity. METHODS AND MATERIALS: A total of 100 Japanese men with prostate cancer underwent (192)Ir HDR brachytherapy combined with hypofractionated EBRT. Mean (SD) dose to 90% of the planning target volume was 6.3 (0.7) Gy per fraction of HDR. After 5 fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administrated. The urethral volume receiving 1-15 Gy per fraction in HDR brachytherapy (V1-V15) and the dose to at least 5-100% of urethral volume in HDR brachytherapy (D5-D100) were compared between patients with Grade 3 toxicity and those with Grade 0-2 toxicity. Prostate volume, patient age, and International Prostate Symptom Score were also compared between the two groups. RESULTS: Of the 100 patients, 6 displayed Grade 3 acute GU toxicity, and 12 displayed Grade 3 late GU toxicity. Regarding acute GU toxicity, values of V1, V2, V3, and V4 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0-2 toxicity. Regarding late GU toxicity, values of D70, D80, V12, and V13 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0-2 toxicity. CONCLUSIONS: The severity of GU toxicity in HDR brachytherapy combined with hypofractionated EBRT for prostate cancer was relatively high. The volume of prostatic urethra was associated with grade of acute GU toxicity, and urethral dose was associated with grade of late GU toxicity.

Four-year experience of interstitial permanent brachytherapy for Japanese men with localized prostate cancer.

OBJECTIVE: To report 4 year results obtained with our initial 100 patients with localized prostate cancer treated by interstitial permanent brachytherapy. METHODS: One-hundred Japanese men with clinically localized prostate cancer underwent interstitial permanent prostate brachytherapy using (125)I seeds. Median follow-up was 36 months (range, 30-42 months). Median initial prostate-specific antigen (PSA) level was 6.7 ng/ml (range, 1.5-25.2 ng/ml). Of these 100 patients, 31 received neoadjuvant hormone therapy for several months. Treatment morbidities were assessed using Radiation Therapy Oncology Group (RTOG) scale and National Cancer Institute Common Toxicity Criteria. RESULTS: A mean of 95 seeds (range, 48-123 seeds) were successfully implanted in patients with prostate cancer. Mean prostate volume receiving at least 100% dose (V100) and dose to 90% of prostate volume (D90) for the 100 patients were 96.6% and 166.1 Gy, respectively. Urinary morbidity was common, but was usually not severe. Only four patients needed catheterization for urinary retention (Grade 3) during follow-up. Most patients displayed no rectal morbidity after implantation, with only 3% of patients showing RTOG Grade 2 rectal morbidity and no patients showing morbidity of Grade 3 or more. Three patients experienced biochemical failure according to Phoenix consensus definition during follow-up. One patient displayed clinical failure with lymph node recurrence. CONCLUSIONS: These results indicate that interstitial permanent brachytherapy is safe and effective for Japanese patients with localized prostate cancer. The import of matured techniques developed in Western countries might allow bypass of the trial-and-error process in Japanese institutions.

[Sudden death after 125I brachytherapy in prostate cancer patient: a case report].

A management of 125I isotope is defined by medical guideline from Ministry of Health, Labour and Welfare in Japan. According to this, when the patient died within one year after 125I interstitial permanent prostate brachytherapy, we have to do autopsy and collect all implanted isotopes as soon as possible. We report here, a 70-year-old man who underwent 125I interstitial permanent prostate brachytherapy for localized prostate cancer and one month after brachytherapy the patient died of acute cerebral hemorrhage, which was unrelated to the 125I brachytherapy. Autopsy was performed and collection of migrated isotopes was extremely difficult in technically. In addition, the cost of autopsy and distance from our hospital were also problems in this case. Treatment of prostate cancer with brachytherapy has increased in Japan, and we should establish management manual for sudden death case after 125I brachytherapy.

Cancer core distribution in patients diagnosed by extended transperineal prostate biopsy.

OBJECTIVES: To perform systemic 22-core transperineal ultrasound-guided template prostate biopsies in patients with previous negative transrectal ultrasound-guided prostate biopsy findings and evaluate the cancer core distribution. METHODS: Between April 2001 and December 2003, 128 men underwent systemic ultrasound-guided biopsy using the transperineal template technique. All patients had undergone at least one previous set of biopsies. Prostate biopsy was performed transperineally using an 18-gauge biopsy needle driven by a spring-loaded device. Four biopsies were obtained anterior to posterior from each of four coronal planes in the mid-region, and three biopsies were obtained anterior to posterior from each of two coronal planes in the apical region. RESULTS: Of the 128 patients, 29 (22.7%) had cancer according to an extended transperineal biopsy. Patients with prostate cancer had significantly greater prostate-specific antigen (PSA) levels (11.4 versus 7.6 ng/mL, P = 0.0125), smaller transition zone volumes (12.7 versus 21.2 cm3, P = 0.0012), smaller prostate glands (31.5 versus 44.0 cm3, P = 0.0015), and greater PSA density (0.36 versus 0.19 ng/mL/cm3, P < 0.0001). The cancer core rates in the mid and apical parts of the anterior region (5.3% and 8.0%) were significantly greater than in the mid and apical parts of the posterior region (3.3% and 3.6%, P = 0.0297 and P = 0.0132, respectively). CONCLUSIONS: The results of our study have shown that transperineal approaches are appropriate for sampling from the anterior half of the prostate gland. In patients in whom the diagnosis of prostate cancer is suspected, we believe that systemic 22-core transperineal ultrasound-guided template prostate biopsy might be the next optional diagnostic step after an initial negative prostate biopsy.

High molecular mass proteome of androgen-independent prostate cancer.

We made a comprehensive study of protein expression of androgen-independent (AI) prostate cancer by means of agarose two-dimensional gel electrophoresis (agarose 2-DE) followed by liquid chromatography-tandem mass spectrometric analysis. The agarose 2-DE method being good at separating high molecular mass (HMM) proteins and alkaline ones, so we were able to successfully reveal differences between the proteomes of androgen-dependent (AD) tumors and those of AI tumors. During the creation of agarose 2-DE protein maps, we successfully identified 295 proteins (91.0%) out of 324 spots excised in total. Excluding redundant and mouse serum proteins, we considered the remaining 225 proteins to be related to the cancer. We divided the 225 cancer-related proteins into HMM and low molecular mass (LMM) groups by their molecular mass being above or below 80 kDa. Functional classification of the proteins in these two groups showed clear differences between the two: more than half (54.8%) of the HMM proteins, but less than one-third (29.1%) of the LMM ones were classified among transcription- or translation-related proteins. Eighteen proteins were regulated when the tumor progressed from an AD to an AI state. Five of these proteins, including antioxidant protein 2, superoxide dismutase 1, thioredoxin peroxidase, GTP-binding protein beta chain homolog, and the ha1225 gene product, had a function to protect cells against oxidant stress-induced apoptosis. We suggest that prevention against oxidative stress is one of the key points for prostate cancer to obtain androgen independency. We also found proteins that had not been previously reported in prostate cancer by use of genomic or conventional 2-DE based proteomic approaches. The proteomic approach, using agarose 2-DE focused on HMM proteins, has the capability to find novel biomarkers of prostate cancer.

[Cases of bacillus Calmette-Guerin-induced granulomatous prostatitis and prostatic stromal invasion of the bladder carcinoma in situ, showing similar clinical findings].

Intravesical instillation of bacillus Calmette-Guerin (BCG) is the first-line therapeutic option for flat carcinoma in situ (CIS) of the bladder. Intravesical BCG instillation has been demonstrated to cause granulomatous prostatitis. Bladder CIS often also is known to show prostatic stromal invasion. We report a case of BCG-induced granulomatous prostatitis and a case of prostatic stromal invasion of bladder CIS accompanied by locally advanced prostate cancer, which showed similar clinical findings after the intravesical BCG therapy. In these 2 patients, urinary symptoms such as dysuria were prolonged regardless of anti-tuberculous medication, hard nodules were palpable at the prostate, and hypoechoic lesions were visualized by transrectal ultrasound. Both patients were treated by transurethral resection of the prostate, and the diagnoses were made by histopathological examination. Urinary symptoms were resolved in both patients after surgery, but the prostatic stromal tumor showed recurrence of growth. We report the usefulness of transurethral resection of the prostate for medication-resistant BCG-induced granulomatous prostatitis, and the importance of the correct diagnosis of prostatic stromal invasion of bladder CIS especially in the cases with concurrent prostate cancer.