Correlation Between Nitric Oxide and Urodynamics in Men With Bladder Outlet Obstruction / 대한배뇨장애요실금학회지

Purpose@#To investigate the correlation between nitric oxide (NO) and urodynamics in men with bladder outlet obstruction (BOO) by analyzing nitric oxide synthase (NOS) in the urothelium. @*Methods@#We prospectively enrolled 25 men who planned to undergo surgical treatment for benign prostatic obstruction and identified as BOO in the preoperative urodynamics. Bladder tissue was taken during surgical prostate resection. Expressions of endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) in the urothelium were analyzed, and their correlation with urodynamic parameters was also assessed in all patients. We also compared the expressions of eNOS, iNOS, and nNOS between BOO with detrusor underactivity (DU) group and BOO without DU group. @*Results@#In all patients, the level of eNOS positively correlated with maximal flow rate and with maximum cystometric capacity (MCC). The level of iNOS positively correlated with MCC. nNOS levels were positively correlated with detrusor pressure at maximal flow and with bladder contractility index in all patients. The level of eNOS, iNOS, and nNOS did not significantly differ between BOO without DU group and BOO with DU group. @*Conclusions@#This study suggests that NO was correlated with bladder dysfunction in men with BOO. Particularly, nNOS may reflect the change in detrusor function.

Effect of the Sodium-Glucose Cotransporter 2 Inhibitor, Dapagliflozin, on Genitourinary Infection in an Animal Model of Type 2 Diabetes / 대한배뇨장애요실금학회지

Purpose@#To investigate the effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, on inflammatory cytokines of urogenital tissue in a rat model of type 2 diabetes (T2DM) to infer pharmaceutical influence of dapagliflozin on genitourinary infection or inflammation. @*Methods@#Study animals were divided into the following 4 groups of 10 animals each: (1) the Otsuka Long-Evans Tokushima Fatty (OLETF)-DA group treated with dapagliflozin at 1.0 mg/kg/day, (2) the OLETF-VO group treated with voglibose at 0.6 mg/kg/day, (3) the control group (OLETF-CO) given water, and (4) the Long-Evans Tokushima Otsuka (LETO) rats were included as nondiabetic control group. Changes in blood glucose, 24-hour urine volume, and urine glucose were measured. The interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels in the bladder and the urethra were quantified, respectively. @*Results@#The urine glucose level and the 24-hour urine volume at 12 weeks of treatment were significantly higher in the OLETF-DA group than that in any other group (P<0.05). The cytokine analysis of the bladder and urethra showed higher IL18 and IL-1β in the OLETF-DA and the OLETF-CO groups than that in the OLETF-VO and LETO groups (P<0.05). The cytokine levels did not differ between the OLETF-DA and the OLETF-CO groups, and the level of IL-18 in the OLETF-DA group was higher in the urethra than in the bladder. @*Conclusions@#This study revealed that dapagliflozin increased the urine glucose concentration, resulting in an inflammatory response remain in the urogenital tract as the untreated diabetic rats. Therefore, when treating patients with T2DM with dapagliflozin, careful attention should be paid to genitourinary infection or inflammation.

Inhibition of Proliferation of Prostate Cancer Cell Line DU-145 in vitro and in vivo Using Salvia miltiorrhiza Bunge / 中国结合医学杂志

OBJECTIVE@#To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge. (SM) on the castration-resistant prostate cancer (CRPC) cell line DU-145, in vitro and in vivo.@*METHODS@#Prostate cancer cell line (DU-145) and normal prostate cell line (RWPE-1) were treated with SM at different concentrations (3.125, 12.5, 25 and 50 μg/mL) to investigate the antiproliferative effects. DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells. Molecular mechanism was investigated by Western blot analysis of p53, Bcl-2, prostate specific antigen (PSA), and androgen receptor (AR). Six-week-old male BALB/c nude mice were randomly divided into normal control group (n=101) and treated group (n=101) which administered 500 mg/kg SM for 2 weeks. Tumor volumes were measured.@*RESULTS@#Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with RWPE-1. DNA laddering analysis indicated the apoptosis of DU-145 cells. Treatment with SM increased the expression of p53 and reduced the expression of Bcl-2 proteins. The levels of PSA were considerably reduced in SM-treated group compared to the controls, and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in PSA. In the tumour xenograft study, SM given once a day for 2 weeks significantly inhibited tumour growth.@*CONCLUSION@#SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.

The Effect of Daily Low Dose Tadalafil on Cerebral Perfusion and Cognition in Patients with Erectile Dysfunction and Mild Cognitive Impairment

OBJECTIVE: The aims of this study were to investigate the effects of daily low-dose tadalafil on cognitive function and to examine whether there was a change in cerebral blood flow (CBF) in patients with erectile dysfunction (ED) and mild cognitive impairment. METHODS: Male patients aged 50 to 75 years with at least three months of ED (International Index of Erectile Function [IIEF]-5 score ≤ 21) and mild cognitive impairment (Montreal Cognitive Assessment [MoCA] score ≤ 22) were included in the study. The subjects were prescribed a low-dose PDE5 inhibitor (tadalafil 5 mg) to be taken once daily for eight weeks. Changes in MoCA score and single-photon emission computed tomography (SPECT) study between the two time-points were assessed by paired t tests. RESULTS: Overall, 30 male patients were assigned to the treatment group in this study and 25 patients completed the eight-week treatment course. Five patients were withdrawn due to adverse events such as myalgia and dizziness. Mean baseline IIEF and MoCA scores were 7.52 ± 4.84 and 18.92 ± 1.78. After the eight-week treatment, mean IIEF and MoCA scores were increased to 12.92 ± 7.27 (p < 0.05) and 21.8 ± 1.71 (p < 0.05), respectively. Patients showed increased relative regional CBF in the postcentral gyrus, precuneus, and brainstem after tadalafil administration versus at baseline (p < 0.001). CONCLUSION: The results of this prospective clinical study suggest that daily use of tadalafil 5 mg increases some regional CBF and improves cognitive function in patients with ED and mild cognitive impairment.

Effect of Korean Herbal Formula (Modified Ojayeonjonghwan) on Androgen Receptor Expression in an Aging Rat Model of Late Onset Hypogonadism

PURPOSE: Testosterone replacement therapy is an effective treatment for late-onset hypogonadism (LOH) despite a few contraindications and side-effects. The aim of this study was to determine whether modified Ojayeonjonghwan (KH-204, Korean herbal formula) improved LOH. KH-204 is a strong antioxidant herbal formula. We evaluated the effect of Korean herbal prescription on androgen receptor (AR) expression in an aged rat model of LOH. MATERIALS AND METHODS: Eighteen-month-old rats were used as aged LOH rat models. Eighteen Sprague-Dawley rats were randomly divided into three equal groups of six animals each and treated with one of the following: 1) normal control group (oral administration with distilled water, n=6), 2) KH-204 200 group (oral administration with 200 mg/kg of KH-204, n=6), and 3) KH-204 400 group (oral administration with 400 mg/kg of KH-204, n=6). After four weeks of treatment (once daily, distilled water or KH-204), serum testosterone levels, changes in testicular and epididymal weight, Western blotting analysis of AR expression and measurement of oxidative stress were examined. RESULTS: Treatment with the herbal formulation KH-204 200 mg/kg and 400 mg/kg (1) increased the weights of testis and epididymis; (2) increased the level of serum testosterone; (3) increased the level of superoxide dismutase and reduced the level of 8-hydroxy-20-deoxyguanosine; and (4) upregulated AR expression in testicular tissue. CONCLUSIONS: KH-204 might be an effective alternative for LOH. It improves antioxidant mechanisms and increases testicular AR expression without side-effects.

Efficacy and Safety of Incontinence Surgery According to the Surgeon’s Specialty and Performance of a Preoperative Urodynamic Study / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to analyze the efficacy and to estimate the complication rate of incontinence surgery according to the surgeon's specialty and whether a preoperative urodynamic study (UDS) was performed, using a nationally representative dataset. METHODS: We enrolled 356,155 women over 20 years old who had undergone surgery for stress urinary incontinence between 2006 and 2015. Patients were followed for up to 3 years to analyze the reoperation and complication rates. Data were obtained from the National Health Claims Database of the National Health Insurance Service (NHIS) of Korea. Multiple Cox regression analysis was conducted to examine the efficacy and safety of incontinence surgery according to the surgeon’s specialty and whether a preoperative UDS was performed. RESULTS: The hazard ratio (HR) for reoperation was significantly higher for procedures performed by nonurologists than for procedures performed by urologists (HR, 1.174; 95% confidence interval [CI], 1.103–1.249). Acute urinary retention, postoperative infections, procedure-associated pain, and other complications were also more common in procedures performed by nonurologists than in those performed by urologists. When stratified by whether a preoperative UDS was performed, the HR for reoperation according to the surgeon’s specialty varied by performance of a preoperative UDS. While the reoperation rate was significantly higher in procedures performed by non-urologists when a preoperative UDS was performed (HR, 1.208; 95% CI, 1.122–1.3), there was no significant difference in the HRs for reoperation according to specialty when a preoperative UDS was not performed. CONCLUSIONS: This population-based study showed that the postoperative outcomes of incontinence surgery were dependent upon the surgeon’s specialty and that the reoperation rate according to the surgeon’s specialty varied based on whether a preoperative UDS was performed.

Factors Associated With Early Recovery of Stress Urinary Incontinence Following Holmium Laser Enucleation of the Prostate in Patients With Benign Prostatic Enlargement / 대한배뇨장애요실금학회지

PURPOSE: To investigate factors associated with early recovery of stress urinary incontinence (SUI) following holmium laser enucleation of the prostate (HoLEP) in patients with benign prostatic enlargement (BPE). METHODS: The medical records of 393 patients who underwent HoLEP for BPE were retrospectively reviewed. Patients with SUI following HoLEP were selected and divided into 2 groups: those who experienced early recovery of SUI and those who experienced persistent SUI. Recovery of SUI within 1 month after HoLEP was defined as early, and SUI that remained present after 1 month was defined as persistent. Preoperative clinical and urodynamic factors, as well as perioperative factors, were compared between groups. RESULTS: SUI following HoLEP was detected in 86 patients. Thirty-three patients exhibited recovery of SUI within 1 month, and SUI remained present in 53 patients after 1 month. Multivariate analysis showed that the transition zone prostate volume (odds ratio [OR], 5.354; 95% confidence interval [CI], 1.911–14.999; P=0.001) and the enucleation ratio (OR, 8.253; 95% CI, 1.786–38.126; P=0.007) were significantly associated with early recovery of SUI. CONCLUSIONS: Early recovery of SUI within 1 month following HoLEP was associated with transition zone prostate volume and the enucleation ratio.

Administration of Goji (Lycium chinense Mill.) Extracts Improves Erectile Function in Old Aged Rat Model

PURPOSE: This study investigated the effect of goji (Lycium chinense Mill.) on erectile dysfunction in old-aged rats. MATERIALS AND METHODS: Twenty-four 18-month-old male Sprague-Dawley rats (defined as old-aged rats) were used. Treatment groups contained eight rats each: a control group, goji extract of 150 mg/kg/day group, and goji extract of 300 mg/kg/day group. Treatment was by orogastric tube once daily for 6 weeks. After 6 weeks of treatment, testes weight, serum testosterone, superoxide dismutase, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, intracavernous pressure/mean arterial pressure, and histological changes were examined. RESULTS: Treatments with goji extracts increased serum testosterone level, increased the expression of endothelial NO synthase, neuronal NO synthase, and cGMP, improved the oxidative stress marker, and decreased corporal fibrosis. CONCLUSIONS: Our results indicate that goji extract may have a positive effect on erectile dysfunction via its antioxidant effects.

Development of an Improved Animal Model of Overactive Bladder: Transperineal Ligation versus Transperitoneal Ligation in Male Rats

PURPOSE: We compared a transperineal ligation model and a transperitoneal ligation model in male rats to determine which animal model of overactive bladder (OAB) was more useful based on cystometrography, estimations of oxidative stress, and measurements of pro-inflammatory cytokine levels. MATERIALS AND METHODS: Male rats were randomly divided into three groups (n=15 in each): the control group, the transperineal ligation group, and the transperitoneal ligation group. Four weeks after the ligation procedure, cystometrography was performed and oxidative stress, pro-inflammatory cytokine levels, and histologic changes were evaluated. Oxidative stress was assessed by measuring 8-hydroxy-20-deoxyguanosine and superoxide dismutase, and pro-inflammatory cytokine activity was investigated by measuring levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α. RESULTS: The transperineal model led to results similar to those observed for the transperitoneal model, namely (1) increased voiding frequency and reductions in the non-voiding contraction interval and the maximal vesical pressure, (2) increased levels of oxidative stress markers, (3) increased pro-inflammatory cytokine levels, and (4) fibrotic changes in the bladder tissue. CONCLUSIONS: We suggest that the transperineal procedure can be used as an alternative OAB model in male rats.

Anti-Inflammatory and Antimicrobial Effects of a Novel Herbal Formulation (WSY-1075) in a Chronic Bacterial Prostatitis Rat Model

PURPOSE: The aim of this study was to investigate the anti-inflammatory and anti-oxidative effects of a multi-herbal formula known as WSY-1075 in the treatment of chronic bacterial prostatitis in a rat model. MATERIALS AND METHODS: Experimental chronic bacterial prostatitis was induced in 32 Wistar rats by instillation of a bacterial suspension (Escherichia coli, 10⁸ colony-forming units [CFU]/mL) into the prostatic urethra. After the induction of prostatitis, the rats were randomly divided into one of 4 treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (400 mg/kg) (n=8), and WSY-1075 (400 mg/kg)+ciprofloxacin (n=8). After 4 weeks of treatment, microbiological data from prostate tissue cultures, level of prostatic pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-8), anti-oxidant effects (superoxide dismutase [SOD]), and histological findings were noted. RESULTS: The WSY-1075, ciprofloxacin, and WSY-1075+ciprofloxacin groups showed fewer CFUs in prostate tissue cultures than the control group. The WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups showed statistically significantly lower levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8 than the control group. SOD levels in the WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups were significantly higher than in the control group. CONCLUSIONS: This study found that WSY-1075 had anti-microbial effects, anti-inflammatory effects, and anti-oxidative effects in a chronic bacterial prostatitis rat model. We expect the WSY-1075 may be useful for the clinical treatment of chronic bacterial prostatitis.

Protective Effects of KH-204 in the Bladder of Androgen-Deprived Rats

PURPOSE: We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats. MATERIALS AND METHODS: Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment. RESULTS: Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis. CONCLUSIONS: Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity.

Changes in Clinicopathological Characteristics of Renal Cell Carcinoma in the Past 25 Years: A Single-Center Experience

PURPOSE: We examined changes in the clinicopathologic characteristics of renal cell carcinoma (RCC) in the past 25 years and aimed to obtain indicators for its diagnosis and treatment. MATERIALS AND METHODS: The medical records of 563 patients with confirmed primary RCC after surgical treatment from 1985 to 2010 at Seoul St. Mary's Hospital were retrospectively reviewed. Patient and tumor characteristics were compared over 3 time periods (period 1: 1985-1994, period 2: 1995-2004, period 3: 2005-2010). RESULTS: Period 1 included 65 patients, period 2 included 183 patients, and period 3 included 315 patients, showing an exponential growth in the number of patients. Frequency was highest in the late 50s age group. The review of clinical symptoms showed that incidental diagnosis increased significantly. The tumor size at diagnosis gradually decreased and the proportion of small tumors less than 4 cm increased remarkably. Concerning tumor spread, organ-confined tumors (T1-2N0M0) increased and distant metastasis decreased. Histologically, the clear cell type made up the greatest proportion, about 90% in each period, but subtypes besides the clear cell type increased over the study period. The rate of nephron-sparing surgery increased, and exophytic masses were the most common. CONCLUSIONS: Our review of the recent 25 year's worth of data on RCC from Seoul St. Mary's Hospital showed that the incidental diagnosis of RCC increased over the study period in accordance with the development of screening tests. Tumor size decreased in accordance with the progress in imaging modalities. In the future, multicenter research will be needed to analyze the characteristics of whole renal cancer in Korea.

Urodynamic Findings in Patients with Lower Urinary Tract Symptoms and Small Prostate Volumes / 대한남성과학회지

PURPOSE: Lower urinary tract symptoms (LUTS) can be caused by abnormal detrusor activity, bladder outlet obstruction (BOO), or numerous other factors. These factors must be evaluated with scrutiny, especially when prostate volume is small and the patient is about to have invasive treatment. We evaluated the urodynamic findings of patients with LUTS and small prostate volumes. MATERIALS AND METHODS: From January 2006 to December 2008, a total of 140 men with LUTS underwent urodynamic study. Of these 140 men, 51 patients with prostate volume or =8 were evaluated. RESULTS: The average age of the patients was 65.5+/-7.4 years (range 46~86), mean prostate volume was 24.5+/-5.1 (range 13.0~30.0), mean IPSS was 15.5+/-7.7 (range 8~34), and quality of life (QOL) score was 3.4+/-1.5 (range 3~6). BOO was the most common finding, affecting 21 (41.2%) patients. The patients with BOO were significantly older than the unobstructed patients (70.1+/-5.9 and 62.4+/-6.7 years, respectively; p<0.001) and had larger prostates (27.5+/-3.1 and 22.4+/-5.1, respectively; p<0.001). Furthermore, they had higher IPSS, but the difference was not significant (p=0.074). Eighteen (35.5%) patients had normal findings, while detrusor underactivity (DU) was found in 15 (29.4%) and detrusor overactivity (DO) in 3 (5.9%) patients. There was no significant difference in age, prostate volume, or IPSS between men with and without DU. CONCLUSIONS: The most common finding of LUTS with small prostate volume is BOO, even though it accounts for less than half of the patients. However, patients with normal finding or DU on urodynamic study account for majority of cases, emphasizing the value of urodynamic study before invasive treatments.

Laparoscopic Excision of a Congenital Seminal Vesicle Cyst and Coexisting Ipsilateral Renal Agenesis / 대한남성과학회지

Seminal vesicle cyst (SVC) with ipsilateral renal agenesis is a rare congenital anomaly. When the patient is symptomatic, surgical treatment may be necessary. The open surgical approach, traditionally considered the definite form of treatment, has been associated with a high rate of morbidity. The laparoscopic approach for the management of SVCs has recently been described. A 18-year-old man presented with a 2-year history of dysuria and perineal pain. The diagnostic evaluation revealed a 45x35x48 mm sized left seminal vesicle cyst. In addition, he had a solitary, right, functioning kidney, with left renal agenesis. Transperitoneal laparoscopic excision of the cyst was performed successfully. The patient was discharged from the hospital on the fourth postoperative day and did not present with any complaints or complications.