Takashi Hamakawa

Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia.

We investigated the role of the KIT‐mediated mechanism in benign prostatic hyperplasia (BPH), and discuss the pathophysiology of BPH and a candidate target of BPH medical therapy.

Long-Term Survival of a Patient with Invasive Signet-Ring Cell Carcinoma of the Urinary Bladder Managed by Combined S-1 and Cisplatin Adjuvant Chemotherapy

Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor. The disease usually presents at advanced stages because the cancer progresses rapidly. The only option for effective treatment is radical cystectomy, and no effective chemotherapy has been established for this variant. We report a case of signet-ring cell carcinoma of the urinary bladder with a long-term survival of 90 months owing to radical cystectomy and combination adjuvant chemotherapy with S-1 and cisplatin. To our knowledge, this is the first report to demonstrate the long-term therapeutic activity of combination S-1 and cisplatin adjuvant chemotherapy against invasive signet-ring cell carcinoma of the urinary bladder.

Laparoscopic Versus Open Radical Cystectomy for Patients Older than 75 Years: a Single-Center Comparative Analysis

BACKGROUND To explore the safety, efficacy, and oncological outcome of 3-port laparoscopic radical cystectomy (LRC) compared to open radical cystectomy (ORC) in patients older than 75 years. MATERIALS AND METHODS From June 2010 to July 2014, we analyzed 16 radical cystectomies in patients older than 75 years (LRC group=8; ORC group=8). Demographic parameters, operative variables, and perioperative outcome in the 2 groups were retrospectively collected, analyzed, and compared. RESULTS Patients in both groups had comparable preoperative characteristics. A significantly longer operating time (476 vs. 303 min, P=0.0002) and less estimated blood loss (627 vs. 2,106 mL, P=0.021) were observed in the LRC group compared to the ORC group. Infection and ileus were the most common early complications after surgery. Patients who underwent ORC suffered from more postoperative infection (22.2% vs. 0.0%, P=0.054) and ileus (25.0% vs. 12.5%, P=0.521) than the LRC group, but the difference was not significant. CONCLUSIONS Judging from this initial trial, 3-port LRC can be safely carried out in elderly patients. We suggest 3-port LRC as the primary intervention to treat muscle-invasive or high-risk nonmuscle-invasive bladder cancer in elderly patients with an otherwise relatively long life expectancy.

Interleukin-18 may lead to benign prostatic hyperplasia via thrombospondin-1 production in prostatic smooth muscle cells

Although inflammation plays an important role in the development of benign prostatic hyperplasia (BPH), little is known about the exact mechanism underlying this pathogenesis. Here, we investigated the relationship between the inflammatory reaction and BPH.

Chromosomal anomalies and sperm retrieval outcomes of patients with non‐obstructive azoospermia: a case series

Some preoperative factors affecting the outcome of microdissection testicular sperm extraction (micro‐TESE) have been previously evaluated. However, other than Klinefelter syndrome (KS), no other chromosomal anomalies have been discussed in the context of sperm retrieval outcomes. The objective of this study was to describe chromosomal anomalies and their relationship with sperm retrieval outcomes in patients with non‐obstructive azoospermia (NOA). Of the 197 NOA patients whose clinical records were retrospectively reviewed, 144 (73.1%) had normal 46,XY karyotype, 40 (20.3%) had KS (47,XXY), and 13 (6.6%) had other chromosomal anomalies (autosomal in seven cases and sex‐chromosomal anomalies in six). Of the seven patients with autosomal anomalies, two had the reportedly normal variant 46,XY,inv(9)(p12;q13). Testicular volume and serum hormone levels (luteinizing hormone, follicle‐stimulating hormone, and total testosterone) of the patients with chromosomal anomalies other than KS were comparable to those of the patients with normal karyotype. The sperm retrieval rate of the patients with 46,XY karyotype, KS, or other chromosomal anomalies were 27.1%, 22.5%, and 15.4%, respectively, with no statistically significant difference. However, among the samples collected from the 13 patients with chromosomal anomalies other than KS, only those from the two patients with the normal variant 46,XY,inv(9)(p12;q13) contained spermatozoa. Among our series of NOA patients, the incidence of autosomal anomalies was higher than that generally noted among neonates, which suggests that not only sex‐chromosomal anomalies but also autosomal anomalies may affect the development of NOA. Furthermore, our findings suggest that sperm retrieval outcome is more unfavorable in NOA patients with chromosomal anomalies than in NOA patients with 46,XY karyotype or KS, despite the use of micro‐TESE.

Effect of obesity on sperm retrieval outcome and reproductive hormone levels in Japanese azoospermic men with and without Klinefelter syndrome

Obesity is reported to have adverse effects on semen quality and the endocrine system. In this study, we evaluated the effect of obesity on sperm retrieval outcome and reproductive hormone levels in Japanese men with non‐obstructive azoospermia (NOA). This study is based on the clinical records of 217 men [172 with a 46,XY karyotype, 45 with Klinefelter syndrome (KS)] with NOA who underwent microdissection testicular sperm extraction at Nagoya City University Hospital between January 2004 and December 2014. Body mass index (BMI) and serum levels of luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and total testosterone (TT) were measured in all patients. In a subset of patients, bioavailable testosterone (cBAT) also was calculated. Values were evaluated separately in patients with and without KS. Sperm retrieval rates (SRRs) in 46,XY men with a BMI <25 kg/m2 and ≥25 kg/m2 were 29.3% and 18.4%, respectively (p = 0.142), while SRRs in KS men with a BMI <25 kg/m2 and ≥25 kg/m2 were 25.0% and 35.3%, respectively (p = 0.460). TT level in men with a BMI ≥25 kg/m2 was lower than that in men with a BMI <25 kg/m2, regardless of KS status. According to Pearson product‐moment correlation coefficients, TT and cBAT levels tended to have negative correlations with BMI; however, statistical significance was observed only for TT level in 46,XY men (r = 0.340, p < 0.001). LH and FSH levels were negatively correlated with BMI in KS men (r = −0.466, p = 0.001 and r = −0.647, p < 0.001, respectively), but not in 46,XY men. These results suggest that obesity may be irrelevant to sperm retrieval outcome in patients with NOA. The negative correlations between gonadotropins and BMI in patients with KS suggest an underlying suppressive effect on gonadotropin excretion, which is distinctive in obese patients with KS.

A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma

Background: We evaluated the effectiveness of gemcitabine and paclitaxel therapy in patients with metastatic urothelial carcinoma for whom two lines of sequential chemotherapy had been unsuccessful. Methods: A total number of 105 patients who had previously received first-line chemotherapy consisting of gemcitabine and cisplatin or carboplatin, were treated with second-line gemcitabine and docetaxel therapy between June 2006 and May 2015. Of these patients, 15 with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 were administered gemcitabine and paclitaxel as third-line treatment from 2013 after failure of the second-line therapy. For each 21-day cycle, gemcitabine (1000 mg/m2) was administered on days 1, 8, and 15, and paclitaxel (200 mg/m2) on day 1. Patients were assessed for each cycle and any adverse events were noted. Furthermore, a Short Form Health Survey questionnaire was used to assess each patient’s quality of life. Results: Third-line gemcitabine and paclitaxel treatment cycles were undertaken for a median of four times (range 2–9). The disease control rate was 80.0%. After second-line gemcitabine and docetaxel therapy was completed, median progression-free survival and median overall survival were determined as 9.8 and 13.0 months, respectively. The only prognostic factor for overall survival, as determined by univariate and multivariate analyses, was third-line gemcitabine and paclitaxel therapy. Neutropenia (66.7%) and thrombocytopenia (53.3%) were noted as the grade 3 treatment-related toxicities. After two cycles of third-line gemcitabine and paclitaxel therapy, the pre- and post-treatment quality of life scores did not differ significantly. Conclusions: Results demonstrate that third-line combination therapy using gemcitabine and paclitaxel is a feasible option for metastatic urothelial carcinoma patients.

Two-year-old girl with impacted ureteral stone successfully treated with a single session of combined percutaneous nephrostomy and ureteroscopy

Impacted stones frequently cause changes in the ureter, including edema of the ureteral wall, stone embedding in the ureteral mucosa or ureteral bending, which often preclude spontaneous passing of the stone and increase the risk of complications during surgery. When stone impaction is suspected preoperatively, management should be adapted accordingly. However, surgical treatment strategies remain controversial in pediatric patients because of the scarcity of cases reported. We describe the case of a 2‐year‐old girl with a right impacted ureteral stone who presented with gross hematuria and pyuria, but no metabolic risk factors or hematological abnormalities. Ureteroscopy was carried out in the presence of a percutaneous nephrostomy catheter. At the 7‐month follow up, hydronephrosis had improved from grade 3 to grade 1, and the ureter was free from residual or recurrent stones. No complications were noted. We believe that percutaneous nephrostomy before the lithotripsy facilitates treatment for impacted stones in pediatric patients.

Mineralocorticoid receptor stimulation induces urinary storage dysfunction via upregulation of epithelial sodium channel expression in the rat urinary bladder epithelium

We aimed to evaluate mineralocorticoid receptor (MR) expression in rat bladder and the physiological role of the MR-epithelial sodium channel (ENaC) pathway in controlling bladder function in 10-12-week-old, male Sprague-Dawley rats. First, we examined the mRNA expression of MR and localization of MR and ENaC-α proteins in the urinary bladder. MR mRNA expression was observed in untreated-rat urinary bladders, and MR and ENaC-α proteins were localized in the epithelium. Next, rats were treated with vehicle (controls) or fludrocortisone (an MR agonist) for 3 days, and ENaC-α protein expression levels and bladder function were evaluated on day 4. ENaC-α protein expression was significantly higher in fludrocortisone-treated rats than in controls. In addition, cystometry was performed during intravesical infusion of saline and amiloride (an ENaC inhibitor). While intercontraction intervals (ICIs) during saline infusion were significantly shorter in the fludrocortisone group than in the controls, infusion of amiloride normalized the ICIs in the fludrocortisone group. However, no intra- or inter-group differences in maximum intravesical pressure were observed. Taken together, MR protein is localized in the rat urinary bladder epithelium, and may regulate ENaC expression and bladder afferent input. The MR-ENaC pathway may be a therapeutic target for ameliorating storage symptoms.

Neuroendocrine Carcinoma of the Kidney and Bladder with Loss of Heterozygosity and Changes in Chromosome 3 Copy Number

Patient: Female, 77 Final Diagnosis: Neuroendocrine carcinoma of the kidney and bladder Symptoms: Right lumbar pain Medication: None Clinical Procedure: CT • needele biopsy of renal tumor • transyrethral resection of bladder tumor Specialty: Urology Objective: Rare disease Background: Neuroendocrine carcinomas (NECs) of the urological organs are observed occasionally, although simultaneous development in the kidney and blabber has not been reported. Case Report: We report a case of a metastatic NEC of the kidney and bladder in a 77-year-old woman who underwent renal biopsy and transurethral resection of the bladder tumor. Pathological examination revealed NEC in the kidney and the bladder samples. Immunohistochemical examination revealed strongly positive staining for synaptophysin, chromogranin A, and CD56, and focally positive staining for cytokeratin AE 1/3 and Cam 5.2. Fluorescence in situ hybridization confirmed the increased chromosome 3 copy number, and loss of hybridization in 3q21, 5q22–23, 10q26, and 13q14 was detected when the tumor samples were compared with normal samples. Conclusions: This is a rare case of NEC-specific genetic abnormalities in a kidney-derived tumor, and is the first report to identify kidney-derived NEC that metastasized to the bladder via the urinary tract.