Yukihiro Umemoto

Kidney Stone Formation is Positively Associated with Conventional Risk Factors for Coronary Heart Disease in Japanese Men

PURPOSE We investigated the association between kidney stones and coronary heart disease risk factors in Japanese men. MATERIALS AND METHODS This cross-sectional study included 13,418 Japanese men 30 to 69 years old who voluntarily underwent medical examination between April 1995 and March 2001. Participants were divided into controls, and past and current kidney stone formers based on ultrasound results and medical history. We evaluated conventional risk factors of coronary heart disease, including overweight/obesity, hypertension, diabetes mellitus, gout/hyperuricemia, dyslipidemia and chronic kidney disease. Associations between coronary heart disease risk factors and kidney stones were investigated. RESULTS Of the 13,418 participants 404 current kidney stone formers (3.0%) had kidney stones on ultrasound and 1,231 past kidney stone formers (9.2%) had a history of kidney stones but no kidney stones on medical examination. Body mass index, systolic and diastolic blood pressure, and serum uric acid were significantly higher in past and current kidney stone formers than in controls. Logistic regression analysis indicated that the multivariate adjusted OR for overweight/obesity, hypertension, gout/hyperuricemia and chronic kidney disease significantly increased in the order corresponding to controls, and past and current kidney stone formers. CONCLUSIONS Kidney stone formers, even past stone formers, are likely to have accumulated risk factors for coronary heart disease. They could be preferentially targeted for coronary heart disease prevention.

Inverse Relationship Between Obesity and Serum Prostate-Specific Antigen Level in Healthy Japanese Men: A Hospital-Based Cross-Sectional Survey, 2004-2006

OBJECTIVES To confirm an inverse relationship between obesity and serum prostate-specific antigen (PSA) levels in Japanese men with a smaller body mass index (BMI) than white and African-American men. METHODS We analyzed 5246 apparently healthy Japanese men aged >20 years who visited our medical center for a health checkup from January 2004 to December 2006. The men were divided into 6 groups by age decade, and the BMI was categorized into 5 groups. The body fat percentage (BFP) was also used and was grouped into quartiles. The Mantel-Haenszel chi(2) test was used to check for trends in proportions of subjects with abnormal PSA values for each cutoff point (2.5 and 4.0 ng/mL) in these groups. The relationships between the PSA levels and BMI or BFP were examined using multivariate analysis. RESULTS The median age, BMI, BFP, and PSA level was 46 years, 23.2 kg/m(2), 21.5%, and 0.78 ng/mL, respectively. The proportion of subjects with an abnormal PSA value increased significantly with age (P for trend < .0001); however, no trends were found across the BMI or BFP categories. The geometric mean PSA level increased significantly with age (P for linear trend < .0001) and decreased with BMI and BFP categories (P for linear trend = .001 and P for linear trend = .002, respectively). CONCLUSIONS Our findings have demonstrated an inverse relationship between obesity and PSA levels even in Japanese men with a low prevalence of obesity, such as was previously reported for American men. Therefore, in prostate cancer screening, obesity, which can affect the accuracy of PSA testing, independent of race and ethnicity, should be taken into account.

Pitfalls with MRI Evaluation of Prostate Cancer Detection

Introduction: To assess differences between MRI findings and histopathologically defined prostate cancer localization, we compared clinical results with mapping of radical prostatectomy specimens, and conducted a retrospective MRI cancer localization re-assessment by a urologist-technician after surgery. Methods: We performed MRI for a total of 37 suspected prostate cancer patients. Subsequently, all underwent retropubic radical prostatectomy after prostate biopsy for confirmation of the diagnosis. All the specimens were studied histopathologically with serial sectioning using a whole organ approach. Results: Of the 37 patients, 26 had positive MRI findings. All the surgical specimens contained cancerous lesions, and 23 had multiple foci. Twenty-four of the MRI-positive cases (92.3%) demonstrated coincidence of both MRI and histopathologically defined lesions. In the single focus cases, 78.6% (11/14) demonstrated exact coincidence, but in the multifocal cases there were no cases with exact coincidence of MRI and histopathological findings (0/23). Conclusion: MRI evaluation cannot be considered an effective diagnostic tool in itself for detection of prostate cancers because sensitivity is far from satisfactory, especially in multi-focal cases.

Role of transcription factors Ad4bp/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia

Background:  Ad4bp/SF‐1 and DAX‐1 are orphan members of the nuclear hormone receptor superfamily of transcription factors. In order to obtain better understandings of human testicular steroidogenesis and spermatogenesis, we examined the expression levels of both factors in human normal and idiopathic azoospermic testes and investigated their physical meaning.

Ureteral advancement in patients undergoing laparoscopic extravesical ureteral reimplantation for treatment of vesicoureteral reflux.

PURPOSE Laparoscopic extravesical ureteral reimplantation for vesicoureteral reflux has gained acceptance as a feasible treatment associated with minimal morbidity. However, ureteral advancement with this technique has not been attempted. We examined the usefulness of ureteral advancement via laparoscopy. MATERIALS AND METHODS A total of 30 patients with 51 refluxing ureters underwent laparoscopic extravesical ureteral reimplantation for treatment of vesicoureteral reflux between August 2009 and September 2011. Mean ± SD patient age was 60.8 ± 48.6 months. During the procedure 15 patients underwent ureteral advancement (advancement group), while 15 did not (nonadvancement group). We compared operative times and postoperative rates of urinary tract infections and persistent reflux between the groups. RESULTS There was no significant difference in operative times in unilateral (mean ± SD 110 ± 25 vs 125 ± 42 minutes) and bilateral cases (mean ± SD 214 ± 52 vs 203 ± 40 minutes) between the nonadvancement vs advancement groups. All patients underwent voiding cystourethrography 3 to 4 months postoperatively. Reflux resolution rate for ureters was significantly higher in the advancement group (100%) than in the nonadvancement group (85%, p <0.05). No patient in the advancement group had postoperative urinary tract infection. Fixation of the ureter with the bladder muscularis at the proximal limit of the detrusor defect and/or a percutaneous hitch stitch placed in the ventral side of the proximal limit of the detrusor defect facilitated ureteral advancement. CONCLUSIONS Ureteral advancement is a simple and feasible procedure in laparoscopic ureteral extravesical reimplantation and may improve the resolution rate of vesicoureteral reflux.

Cyclooxygenase-2 protects germ cells against spermatogenesis disturbance in experimental cryptorchidism model mice.

The role of cyclooxygenases (COX) in the male reproductive organ remains unclear. However, there are some reports suggesting that COX-2 might have an effect on spermatogenesis or steroidogenesis. In this study, we examined whether COX-2 was induced in impaired testes, and we also investigated the possible role of COX in the testes using experimental cryptorchidism model mice. Five-week-old male mice underwent an operation to induce unilateral cryptorchidism via an abdominal incision and suturing of the left testes to the lateral abdominal wall, and they were then divided into 3 groups: 1) experimental cryptorchidism plus SC560 (selective COX-1 inhibitor) administration; 2) experimental cryptorchidism plus NS398 (selective COX-2 inhibitor) administration; 3) and experimental cryptorchidism alone. The expression levels of COX-1 and COX-2 were determined by immunohistologic staining and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The influence of COX inhibitors on the testes was assessed by measuring the concentration of serum testosterone and evaluating the seminiferous tubules according to the Johnsen score. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining was also performed to detect apoptosis in the testes. Immunohistologic staining and RT-PCR revealed that the expression of COX-2 was increased in the experimental cryptorchid testes (groups 1-3). The concentration of serum testosterone was significantly lower in group 2 at 5 weeks after surgery than in the other groups. The Johnsen score of the cryptorchid testes in group 2 was significantly lower than those in other groups at 5 weeks after surgery. TUNEL staining revealed that the number of apoptotic cells was significantly increased in group 2 compared with the other groups. However, the COX-1 inhibitor did not appear to affect spermatogenesis in the experimental cryptorchid testes. These results suggest that the COX-2 inhibitor provoked testicular damage in experimental cryptorchidism by inducing germ cell apoptosis. The expression of COX-2 might be induced to protect germ cells from heat stress caused by experimental cryptorchidism.

Gene transfer to sperm and testis: future prospects of gene therapy for male infertility.

Male infertility has been considered a major contributory factor to infertility. The causes of spermatogenetic failure found in most cases of male infertility remain largely idiopathic. Unfortunately, there is no effective treatment to improve spermatogenesis for idiopathic male infertility patients. Intracytoplasmic sperm injection (ICSI) is the current treatment of choice for severe male infertility and has brought the joy of childbearing to couples for whom it was previously impossible; however, several problems exist with this treatment. In addition, if there are no spermatozoa in the testis of these patients, they do not have paternity potential even if ICSI is conducted. Ultimately, fertilization is better in vivo than in vitro. Recently, on the other hand, gene transfer to sperm and testis has been developed to find more effective and simple methods to obtain transgenic animals. This technique has the potential to be the most useful approach for the future treatment of male infertility. In this review, we will give an overview of the recent advanced technique of gene transfer to sperm and testis, and discuss the future prospects of gene therapy for the treatment of male infertility. In conclusion, although more investigations on the mechanism of spermatogenesis and male infertility and the establishment of techniques for more efficient and safer gene transfer to the sperm and testis will be needed, gene therapy will enable a revolutionary advance for reproductive treatment and provide great benefit for patients with male infertility in the future.

Comparison of laparoscopic pyeloplasty for ureteropelvic junction obstruction in adults and children: lessons learned.

PURPOSE We compare the technical details and surgical outcomes of adult and pediatric laparoscopic pyeloplasty, and discuss the lessons learned from these comparisons. MATERIALS AND METHODS A total of 46 patients underwent laparoscopic pyeloplasty for repair of ureteropelvic junction obstruction between August 2006 and April 2010. Patients were divided into 2 groups-adults (older than 16 years, 21 patients) and children (15 years or younger, 25 patients). Medical records and surgical videos were reviewed with particular attention to patient characteristics, procedures and surgical outcomes. RESULTS Crossing vessels were more common in adults (p <0.05). After June 2009 we tried to perform a transmesenteric approach for left ureteropelvic junction obstruction, and actually performed this procedure for 3 of 5 adults (60%) and 8 of 10 children (80%). There was no significant difference in median operative times between adults and children. However, mean time required for exposure of the ureteropelvic junction in children (54 minutes) was less than that in adults (81 minutes, p <0.005). Mean time required for ureteropelvic anastomosis tended to be longer in children. Postoperative complications were noted in 3 adults and 1 child. Percentage reduction in anteroposterior diameter of the renal pelvis was significantly greater in children than in adults (p <0.05). Successful resolution of ureteropelvic junction obstruction was observed in 90.0% of adults and 95.5% of children. CONCLUSIONS Understanding of the key surgical steps of adult and pediatric laparoscopic pyeloplasty can provide for the improvement of laparoscopic skills, and facilitate procedures in adult and pediatric populations.

Involvement of calpain for apoptosis in dysfunction of the unaffected testis in rats with experimental testicular torsion

PROBLEM: The dynamics of calpain and involvement of apoptosis in sperm formation disorder of the unaffected testis in rats with experimental testicular torsion were investigated.
 METHODS OF STUDY: Using 6‐week‐old Wistar rats, an experimental unilateral testicular torsion model was prepared. The bilateral testes were excised 1, 3, 5, 7, 14, 35, and 70 days after the left testis was twisted, and the unaffected testes were subjected to immunohistological staining, sodium dodecyl sulfate polyacrilamide gel electrophoresis and Western blotting using anti‐calpain antibodies. Apoptosis was detected by the TdT‐mediated dUTP–biotin nick end‐labeling (TUNEL) method.
 RESULTS: By immunohistological staining, positive immunostaining by anti‐pro μ‐calpain antibody was observed in the spermatocyte nucleus, but not with anti‐pro m‐calpain antibody. The staining was increased until 7 days after testicular torsion, then decreased with progression of sperm formation disorder. By Western blotting, the intensity of staining with anti‐pro μ‐calpain antibody was increased until 7 days after torsion of the testis. Apoptosis expression in the unaffected testis was significantly inhibited by addition of a calpain inhibitor.
 CONCLUSIONS: It was suggested that μ‐calpain may be involved in apoptosis expression in sperm formation disorder of the unaffected testis in unilateral testicular torsion.

Usefulness of Transcription Factors Ad4BP/SF-1 and DAX-1 as Immunohistologic Markers for Diagnosis of Advanced Adrenocortical Carcinoma

Background: We examined the expressions of Ad4BP/SF-1 and DAX-1 in primary and metastatic lesions of advanced adrenocortical carcinoma with normal hormonal findings by immunohistochemistry and discussed their usefulness as immunohistochemical markers for diagnosis. Patients and Methods: Four patients (average age 54.3 ± 3.9) with retroperitoneal and metastatic tumors were enrolled in this study. All patients had normal hormonal findings. Ad4BP/SF-1 and DAX-1 underwent immunohistochemical study using needle biopsy specimens from the retroperitoneal tumor or metastatic tumor of these patients to diagnose primary adrenocortical carcinoma. Results: Immunoreactivity for Ad4BP/SF-1 and DAX-1 indicated that it was localized exclusively in the nuclei. Ad4BP/SF-1 immunoreactivity was observed in the carcinoma cells of 2 patients, but not in the others, whereas DAX-1 immunoreactivity was observed in the carcinoma cells of all 4 patients. Conclusion: The expressions of Ad4BP/SF-1 and DAX-1 are considered essential to maintain the biological characteristics of adrenocortical cells even without abnormal hormonal findings or even after malignant transformation and metastasis. These markers are useful to distinguish other retroperitoneal tumors, especially in patients with bulky tumors, and to diagnose the metastatic site of origin as adrenocortical carcinoma in patients clinically presenting with widespread metastasis.