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1.  Inhibitory Role of the Spinal Galanin System in the Control of Micturition 
Urology  2013;82(5):1188.e9-1188.13.
To investigate the effect of intrathecal galanin on the micturition reflex in rats.
Continuous cystometrograms (0.04 mL/min infusion rate) were performed in female Sprague-Dawley rats (225-248 g) under urethane anesthesia. After stable micturition cycles were established, galanin was administered intrathecally to evaluate changes in bladder activity. Then, in order to examine the involvement of opioid systems in the galanin effects, galanin was administered intrathecally when the first bladder contraction was observed after intrathecal administration of naloxone, an opioid receptor antagonist.
Intrathecal administration of galanin (1 to 10 μg) increased intercontraction intervals in a dose-dependent fashion. Intrathecal administration of galanin (1 to 10 μg) also increased pressure threshold in a dose-dependent fashion. These inhibitory effects of galanin (10 μg) were partially antagonized by intrathecal administration of naloxone (10 μg).
These results indicate that in urethane-anesthetized rats galanin delays the onset of micturition through activation of the opioid mechanism, suggesting the inhibitory role of galanin system in the control of the micturition reflex.
PMCID: PMC3920735  PMID: 24035037
2.  The Efficacy of Target Biopsy of Suspected Cancer Lesions Detected by Magnetic Resonance Imaging and/or Transrectal Ultrasonography during Initial Prostate Biopsies: Comparison of Outcomes between Two Physicians 
Yonago Acta Medica  2014;57(1):53-58.
The efficacy of adding target prostate biopsy (PBx) of suspected cancer lesions identified on magnetic resonance imaging (MRI) and/or transrectal ultrasonography (TRUS) to initial systematic PBx was evaluated. Moreover, the outcomes were compared between 2 physicians.
We retrospectively investigated 238 patients who underwent first-time PBx in our hospital. All patients were examined with prostate MRI before PBx. Fourteen systematic biopsies were obtained in all patients. When a suspected lesion was present on MRI and/or TRUS, the lesion was the target of target PBx.
The overall detection rate of prostate cancer (PCa) was 45% (106/238). With target PBx, the PCa detection rate was 32% overall, while that of suspected lesions seen only on MRI was 32%, that of suspected lesions seen only on TRUS was 8% and that of suspected lesions seen on both MRI and TRUS was 52%. The same tendency was shown for each physician. Comparing systematic PBx and target PBx, the overall rate of Gleason score (GS) upgrading with target PBx was 13%. The rate of PCa detected only by systematic PBx was 95%. There was no significant difference between the 2 physicians.
In initial PBx, the addition of target PBx of suspected cancer lesions detected by MRI and/or TRUS to systematic PBx might not be useful to improve the cancer detection rate. However, it may enable more accurate risk classification and detection of minute cancers with a high GS.
PMCID: PMC4110692  PMID: 25067878
magnetic resonance image; prostate cancer; target prostate biopsy; transrectal ultrasonography
3.  Hydronephrosis after retroperitoneal laparoscopic dismembered Anderson–Hynes pyeloplasty in adult patients with ureteropelvic junction obstruction: A longitudinal analysis 
We evaluated the improvement of hydronephrosis longitudinally after laparoscopic dismembered Anderson–Hynes pyeloplasty in adult patients with ureteropelvic junction obstruction.
Material and methods
Sixteen patients underwent laparoscopic pyeloplasty at our institution between January 2006 and June 2012. Hydronephrosis was assessed by ultrasound and intravenous pyelography at 3, 6, 12, 18, and 24 months after pyeloplasty.
The mean follow–up time was 24 months. Preoperative hydronephrosis was diagnosed as grade 2 and grade 3 in 8 patients each. Postoperative improvement of the hydronephrosis by one grade was observed in 56%, 73%, 67%, 50%, and 40% of patients at 3, 6, 12, 18, and 24 months, respectively. Improvement of the hydronephrosis by two grades was observed in 6%, 27%, 33%, 50%, and 60% of patients at 3, 6, 12, 18, and 24 months, respectively. In 5 of 12 patients (42%), hydronephrosis was still improving even after 12 months postoperatively.
Adult patients demonstrate relatively rapid improvements in the degree of hydronephrosis after laparoscopic pyeloplasty and continue to improve for a long time.
PMCID: PMC4074709  PMID: 24982795
adult; hydronephrosis; laparoscopy; pyeloplasty; ultrasonography; pelviureteric junction obstruction
4.  Inhibitory Effect of the Somatostatin Receptor Subtype-4 Agonist NNC 26-9100 on the Micturition Reflex in Rats 
Urology  2012;80(6):10.1016/j.urology.2012.07.007.
To investigate the effects of activation of sst4 on the micturition reflex in rats.
Continuous cystometrograms (0.04 ml/min infusion rate) were performed in female Sprague-Dawley rats (242-265 g) under urethane anesthesia. After stable micturition cycles were established, a selective sst4 receptor agonist, NNC 26-9100, was administered intravenously in normal rats or rats pretreated with capsaicin 4 days before the experiments. Micturition parameters were recorded and compared before and after drug administration.
Intravenous administration of NNC 26-9100 (10 to 300 μg/kg) significantly increased intercontraction interval in dose dependent fashion. Intravenous administration of NNC 26-9100 (10 to 300 μg/kg) also significantly increased pressure threshold in dose dependent fashion. There were no significant changes in baseline pressure, maximum voiding pressure or post-void residual volume. However, NNC 26-9100-induced increases in intercontraction intervals and pressure threshold were not seen in rats with C-fiber desensitization induced by capsaicin pretreatment.
These results indicate that in urethane-anesthetized rats activation of sst4 receptor can inhibit the micturition reflex via suppression of capsaicin sensitive C-fiber afferent pathways. Thus sst4 receptor could be a potential target for the treatment of C-fiber afferent mediated bladder dysfunctions.
PMCID: PMC3829683  PMID: 22951005
bladder; somatostatin; capsaicin; cystometry; rats
5.  Robot-assisted radical prostatectomy: a case series of the first 100 patients -constitutional introduction and implementation on the basis of comprehensive department of minimal invasive surgery center- 
BMC Research Notes  2013;6:436.
Although a very small number of Japanese hospitals had been performing robotic surgery before 2011, the number now using it is increasing rapidly due to the application of health insurance to robotic surgery for prostate cancer (PCa) since April, 2012. We report our initial experience of treating 100 patients by robot-assisted radical prostatectomy (RARP) with a focus on constitutional introduction and implementation based on minimal invasive surgery center (MISC) and patient outcomes.
The MISC involved all of the hospital sections related to robotic surgery including four surgery departments, anesthesiology, operating room nurses, medical engineers. The data were prospectively collected from the first 100 consecutive patients who underwent RARP under supervision of MISC for localized PCa from October 2010 to December 2012.
During the period of our initial 100 cases of RARP, the gynecology, respiratory and digestive surgery departments performed initial cases of 20, 33 and 23 robotic surgeries under control of MISC. Peri-operative complications in RARP appeared to be minimal with no cases of intra-operative open conversion. The positive surgical margin rate was 19% for the entire series. At the median follow-up time of 11.9 months, 91% of patients had undetectable PSA levels, and 76% of patients were not using pads. Sequential urinary functional data indicated a significant beneficial effect on lower urinary tract symptoms beyond cancer control over a period of several months. Although the pre-operative potent patient number was small, the transitions of constant potency recovery at precise time points were shown according to different nerve sparing procedures.
This is the first report of an initial 100 RARP cases that were implemented using the constitutional framework of an academic institution. The MISC is providing immeasurable benefits from the aspects of patient safety and education for the robotic surgical team. RARP is a safe and efficient method for achieving PCa control together with functional preservation, even during the initial trial for this procedure.
PMCID: PMC3874742  PMID: 24171923
Robot-assisted radical prostatectomy; Minimum invasive surgery; Peri-operative complication; Oncological outcome; Functional outcome
6.  Sensory Neuron-Specific Receptor-Mediated Regulation of Micturition Reflex in Urethane-Anesthetized Rats 
Bju International  2011;109(4):628-633.
To investigate the effect of sensory neuron-specific receptors (SNSRs) activation on the micturition reflex in rats.
Continuous cystometrograms (CMG, 0.04ml/min) were performed in female Sprague-Dawley rats under urethane anesthesia. After stable micturition cycles were established, a selective rat SNSR1 agonist, bovine adrenal medulla 8–22 (BAM8-22), was administered intravenously or intrathecally in normal rats or rats pretreated with capsaicin 4 days before the experiments. Micturition parameters were recorded and compared before and after drug administration.
Intravenous administration of BAM8-22 (3 to 100 μg/kg) significantly increased intercontraction intervals in dose dependent fashion, but did not affect residual urine or baseline pressure at any doses tested. Intrathecal administration of BAM8-22 (0.01 to 0.3 μg) also increased intercontraction intervals in dose dependent fashion, but did not affect residual urine or baseline pressure at any doses tested. These inhibitory effects of intravenous (30 μg/kg) or intrathecal (0.3 μg) administration of BAM8-22 were still observed after capsaicin pretreatment.
These results indicate that in urethane-anesthetized rats activation of SNSRs can inhibit the micturition reflex via the pathways independent of capsaicin sensitive C-fibers. Thus SNSRs could be a potential target for the treatment of bladder dysfunction such as overactive bladder.
PMCID: PMC3189417  PMID: 21729234
bladder; sensory-neuron-specific receptors; capsaicin; spinal cord; rats
7.  Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation 
The association of cytochrome P450 aromatase gene CYP19(TTTA)n polymorphism with ovarian response to FSH stimulation was explored.
Three hundred women undergoing medically assisted reproduction and 300 women with at least one spontaneous pregnancy participated in the study. CYP19(TTTA)n polymorphism was genotyped, while serum hormones were determined. During oocyte retrieval, the follicular size, the follicle and oocyte numbers were recorded.
Six CYP19(TTTA)n alleles with 7 to 12 repeats were revealed. Women homozygous for long CYP19(TTTA)n alleles presented with lower serum FSH levels at the third day of the menstrual cycle (p < 0.001) and higher large follicle numbers (p < 0.01), compared to women homozygous for short CYP19(TTTA)n alleles. The CYP19(TTTA)7 allele was associated with higher serum FSH levels (p < 0.003), with lower total follicle (p < 0.02) and large follicle numbers (p < 0.03), while CYP19(TTTA)7 allele-carriers presented more frequently with small follicles than CYP19(TTTA)7 allele-non carriers (p < 0.01).
CYP19 genetic variants were associated with ovarian reserve and response to standard gonadotrophin stimulation of women undergoing in vitro fertilization.
PMCID: PMC3270141  PMID: 22089263
Controlled ovarian stimulation; CYP19; IVF; Ovarian response; Tubal infertility
8.  Low pre–operative levels of serum albumin predict lymph node metastases and ultimately correlate with a biochemical recurrence of prostate cancer in radical prostatectomy patients 
To date, only few studies focusing on the issue of host general and immune activity have been performed in localized prostate cancer (PCa). The aim of this study was to elucidate potent non tumor–related biomarkers that express aggressiveness of PCa treated by radical prostatectomy (RP).
Materials and methods
Data from 179 patients who underwent RP were analyzed. The correlations between various kinds of non tumor–related factors in addition to tumor–related factors and biochemical recurrence (BCR) were analyzed. The correlations between pre–, intra– and post–operative factors were also analyzed.
Thirty–two cases (17.9%) had a BCR. The factors found to be significantly predictive of BCR using a Cox–proportional hazard model were the pre–operative serum prostate specific antigen (PSA) level and the existence of pathological lymph node metastasis (LNM). A low pre–operative serum albumin level (<4.0 g/dl) was significantly correlated with BCR univariately. Logistic regression analysis revealed that a low pre–operative serum albumin level, an American Society of Anesthesiologists (ASA) score above class 2, and a Gleason score above 8 in the biopsy specimens were significantly predictive of pathological LNM.
Tumor–related characteristics are more important for predicting BCR. However, our results suggest that low pre–operative serum albumin level may indicate extensive disease of clinically localized PCa and may ultimately be correlated with BCR. Although multiple reasons may account for the significance of the serum albumin level, it is noteworthy that delayed diagnostic and therapeutic procedures in comorbid patients with low serum albumin levels may lead to PCa progression.
PMCID: PMC3936145  PMID: 24579009
prostatic cancer; radical prostatectomy; prostate–specific antigen; recurrence; serum albumin
9.  Phosphatidylethanolamine N-methyltransferase and choline dehydrogenase gene polymorphisms are associated with human sperm concentration 
Asian Journal of Andrology  2012;14(5):778-783.
Choline is a crucial factor in the regulation of sperm membrane structure and fluidity, and this nutrient plays an important role in the maturation and fertilizing capacity of spermatozoa. Transcripts of phosphatidylethanolamine N-methyltransferase (PEMT) and choline dehydrogenase (CHDH), two basic enzymes of choline metabolism, have been observed in the human testis, demonstrating their gene expression in this tissue. In the present study, we explored the contribution of the PEMT and CHDH gene variants to sperm parameters. Two hundred oligospermic and 250 normozoospermic men were recruited. DNA was extracted from the spermatozoa, and the PEMT −774G>C and CHDH +432G>T polymorphisms were genotyped. The genotype distribution of the PEMT −774G>C polymorphism did not differ between oligospermic and normozoospermic men. In contrast, in the case of the CHDH +432G>T polymorphism, oligospermic men presented the CHDH 432G/G genotype more frequently than normozoospermic men (62% vs. 42%, P<0.001). The PEMT 774G/G genotype was associated with a higher sperm concentration compared to the PEMT 774G/C and 774C/C genotypes in oligospermic men (12.5±5.6×106 spermatozoa ml−1 vs. 8.3±5.2×106 spermatozoa ml−1, P<0.002) and normozoospermic men (81.5±55.6×106 vs. 68.1±44.5×106 spermatozoa ml−1, P<0.006). In addition, the CHDH 432G/G genotype was associated with higher sperm concentration compared to CHDH 432G/T and 432T/T genotypes in oligospermic (11.8±5.1×106 vs. 7.8±5.3×106 spermatozoa ml−1, P<0.003) and normozoospermic men (98.6±62.2×106 vs. 58.8±33.6×106 spermatozoa ml−1, P<0.001). In our series, the PEMT −774G>C and CHDH +432G>T polymorphisms were associated with sperm concentration. This finding suggests a possible influence of these genes on sperm quality.
PMCID: PMC3734977  PMID: 22387881
choline dehydrogenase; male infertility; phosphatidylethanolamine N-methyltransferase; phospholipids; sperm concentration
10.  Reappraisal of intergender differences in the urethral striated sphincter explains why a completely circular arrangement is difficult in females: a histological study using human fetuses 
Anatomy & Cell Biology  2012;45(2):79-85.
To investigate why the development of a completely circular striated sphincter is so rare, we examined histological sections of 11 female and 11 male mid-term human fetuses. In male fetuses, the striated muscle initially extended in the frontal, rather than in the horizontal plane. However, a knee-like portion was absent in the female fetal urethra because, on the inferior side of the vaginal end, a wide groove for the future vestibule opened inferiorly. Accordingly, it was difficult for the developing striated muscle to surround the groove, even though there was not a great difference in width or thickness between the female vestibule and the male urethra. The development of a completely circular striated sphincter seems to be impossible in females because of interruption of the frontal plane by the groove-like vestibule. However, we cannot rule out the possibility that before descent of the vagina, the urethral striated muscle extends posteriorly.
PMCID: PMC3398178  PMID: 22822461
Urethal rhabdosphincter; Genital tract; Urogenital sinus; Colliculus; Human fetus
11.  Serum C-reactive protein level is a significant prognostic indicator in patients with advanced urothelial cancer treated with gemcitabine-cisplatin or carboplatin – preliminary results 
This study determines prognostic factors in patients with advanced urothelial cancer (UC) treated with gemcitabine-cisplatin or carboplatin (GC).
Material and methods
The clinical records of 30 patients with advanced UC treated with GC were retrospectively reviewed. Twenty-six patients (86.7%) had previously undergone other chemotherapies. Hematological parameters such as: neutrophil, lymphocyte and platelet counts; hemoglobin, C-reactive protein (CRP), and albumin levels; pain score; primary tumor site; tumor grade; type of platinum anti-cancer drug; and performance status before treatment were evaluated. Survival rates were calculated using the Kaplan-Meier method and analyzed using the log-rank test. Multivariate analysis was performed using a Cox proportional hazards model.
The median cancer-specific survival (CSS) was 12.5 months. The overall response rate (ORR) was 30.0%. The survival rates of patients with low serum albumin (<3.5 g/dL; P = 0.008), low hemoglobin (<10.1 mg/dL; P = 0.025), high CRP (>1.0 mg/dL; P = 0.001), and a positive pain score (P = 0.002) were significantly worse than those with better blood values and pain scores. Multivariate analysis revealed serum CRP level as an independent prognostic indicator with a hazard ratio of 4.608 (95% confidence interval (CI) of 1.763-12.047; P = 0.002).
Pretreatment serum CRP levels could be an accurate biomarker of the survival of patients with advanced UC before GC therapy. Although this is a preliminary study with a small sample size, these results seem to be very useful in clinical practice and our findings should be confirmed in a larger group of patients.
PMCID: PMC3921783  PMID: 24578930
biomarker; CRP; peripheral blood value; survival; chemotherapy
12.  A case of metastatic renal cell carcinoma treated effectively by gemcitabine and sunitinib 
A 60-year-old man with renal cell carcinoma developed lung metastases after treatment with left radical nephrectomy (pT3bN0M0, clear cell renal carcinoma, Fuhrman G3 >2). The patient received treatment with gemcitabine and interferon-α and achieved complete response after seven cycles of therapy. However, eight months later, local recurrence was discovered in the renal fossa. We changed the therapeutic strategy to sunitinib, a multi-target tyrosine kinase inhibitor. The patient achieved a complete response after twelve cycles of therapy. This case report illustrates the effective use of gemcitabine and sunitinib sequentially for a patient with metastatic renal cell carcinoma.
PMCID: PMC3921806  PMID: 24578969
gemcitabine; sunitinib; metastatic renal cell carcinoma

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