Increased Expression of Neuregulin 1 and erbB2 Tyrosine Kinase in the Bladder of Rats With Cyclophosphamide-Induced Interstitial Cystitis.

PURPOSE: The aim of this study was to evaluate changes in expressions of neuregulin (NRG)1 and erbB2 tyrosine kinase (ErbB2) in bladders of rats with cyclophosphamide (CYP)-induced interstitial cystitis (IC). METHODS: Twenty-four Sprague-Dawley rats were divided into the IC group (n=16) and the control group (n=8). After inducing IC with intraperitoneal CYP injection, expressions of NRG1 and ErbB2 were analyzed using western blotting and reverse transcriptase-polymerase chain reaction. RESULTS: In Western blotting, relative intensities and distributions of both NRG1 and ErbB2 were approximately 1.5- and 3.2-fold higher, respectively, in the IC group than in the control group (mean±standard deviation: 1.42±0.09 vs. 0.93±0.15 and 0.93±0.16 vs. 0.29±0.08, P<0.05). In the rat bladder samples, mRNA expression levels of NRG1 and ErbB2 were higher in the IC group than in the control group (P<0.05). CONCLUSIONS: Our study has demonstrated significant changes in mRNA expression and immunoreactivity of NRG1 and ErbB2 receptors in the urinary bladder after CYP-induced IC. These results suggest that the up-regulated NRG1 may play a role in inducing an overactive bladder and promoting regeneration in the inflammatory bladder with CYP-induced IC.

Expression of brain derived-neurotrophic factor and granulocyte-colony stimulating factor in the urothelium: relation with voiding function.

BACKGROUND: We designed this experiment to elucidate the relationship between the expression of brain derived-neurotrophic factor (BDNF), the expression of granulocyte-colony stimulating factor (G-CSF), and the development of overactive bladder (OAB). In our previous study, the urothelium was observed to be more than a simple mechanosensory receptor and was found to be a potential therapeutic target for OAB. Moreover, neuregulin-1 and BDNF were found to be potential new biomarkers of OAB. Here, we investigated the relationship between changes in the voiding pattern and the expression of BDNF and G-CSF in the urothelium and evaluated the effects of 5-hydroxymethyl tolterodine (5-HMT) on rats with bladder outlet obstruction (BOO). METHODS: A total of 100 Sprague-Dawley rats were divided into the following groups: 20 control rats; 40 BOO rats; and 40 BOO rats administered 5-HMT (0.1 mg/kg). After BOO was induced for 4 weeks, the rats were assessed by cystometrography. The changes in BDNF and G-CSF expression were examined in both separated urothelial tissues and in cultured urothelial cells by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: BOO rats showed increased non-voiding activity [NVA; (number/10 voidings)] and bladder weight and decreased micturition volume (MV), micturition interval (MI), and micturition time (MT) relative to the controls. Moreover, the 5-HMT administration rats showed decreased NVA and bladder weight and increased MV and MI in comparison to the BOO rats. BDNF and G-CSF expression was increased in BOO rats and decreased following 5-HMT administration. In this model, voiding dysfunction developed as a result of BOO. As a therapeutic agent for OAB, the administration of 5-HMT improved the voiding dysfunction. CONCLUSIONS: BDNF and G-CSF might modulate voiding patterns through micturition pathways and might be involved only in the urothelium. Moreover, the expression of both genes in the urothelium might be related to voiding dysfunction in OAB patients. Thus, the urothelium has an important role in the manifestation of voiding symptoms.

Protective effect of N-acetylcysteine against ischemia/reperfusion injury in rat urinary bladders.

Ischemia/reperfusion (I/R) injury represents an important cause of bladder contractile dysfunction. One of the major causes leading to this dysfunction is thought to be reactive oxygen species formation. In this study, we investigated the potential benefit of N-acetylcysteine (NAC), a potent antioxidant that neutralizes free radicals, in a rat model of urinary bladder injury. NAC treatment rescues the reduction of contractile response to I/R injury in a dose-dependent manner. In addition, all levels of reactive oxygen species, lipid peroxidation, and NADPH-stimulated superoxide production in the I/R operation+NAC (I/R+NAC) group also decreased compared with a marked increase in the I/R operation+saline (I/R+S) group. Moreover, an in situ fluorohistological approach also showed that NAC reduces the generation of intracellular superoxides enlarged by I/R injury. Together, our findings suggest that NAC has a protective effect against the I/R-induced bladder contractile dysfunction via radical scavenging property.

Comparison of laparoscopic radiofrequency ablation and open partial nephrectomy in patients with a small renal mass.

PURPOSE: We have performed both open partial nephrectomy (OPN) and laparoscopic radiofrequency ablation (RFA) on selected patients since January 2007 and have been following these patients through serial laboratory assessments and computed tomography (CT). The purpose of the present study was to evaluate long-term oncologic outcomes and renal function status for laparoscopic RFA versus OPN at a minimum follow-up of 3 years. MATERIALS AND METHODS: A total of 55 patients with exophytic, single small renal masses were treated with either OPN (n=14) or laparoscopic RFA (n=41) by a single surgeon. The indications for laparoscopic RFA were as follows: 1) cases with the greatest dimension of the renal mass <3 cm, and 2) cases in which the collecting system, renal calyx, and great vessels were free from the tumor margins by 1 cm. RESULTS: The estimated blood loss (EBL), the operation time, and the mean number of hospital days was significantly lower in the laparoscopic RFA group than in the OPN group. Oncologic data did not differ significantly between the two groups. Creatine clearance levels did not differ significantly compared with those before the operation in either group. CONCLUSIONS: Our data suggest excellent therapeutic outcomes with laparoscopic RFA with achievement of effective operative times, hospital stays, and EBL compared with OPN. According to our indications for laparoscopic RFA, laparoscopic RFA is an effective minimally invasive therapy for the treatment of small renal masses, yielding oncologic outcomes and renal function equivalent to those of OPN.

Is the Expression of Androgen Receptor Protein Associated With the Length of AC Repeats in the Type III 5-α Reductase Gene in Prostate Cancer Patients?

PURPOSE: Type III 5-α reductase (SRD5A3; steroid 5-α reductase 3) may be associated with the progression of prostate cancer (PCa). The aim of our study was to determine whether the length of AC repeats in the SRD5A3 gene is associated with the risk of PCa and the expression of androgen receptor (AR) protein in Korean men. MATERIALS AND METHODS: We compared the length of AC repeats in the short tandem repeat (STR) region of the SRD5A3 gene in 68 PCa patients and 81 control subjects by genotyping. A total of 55 patients in the PCa group underwent radical prostatectomy. We evaluated the expression of AR protein by using Western blotting and tested the association between the type of AC repeats in the SRD5A3 gene and AR protein expression and clinical and pathologic parameters. RESULTS: The short type of STR had less than 21 copies of AC repeats in the SRD5A3 gene. The SS type (short and short type) of STR of the SRD5A3 gene was 2.2 times as likely to occur in PCa patients as in controls (odds ratio, 2.21; 95% confidence interval, 1.14 to 4.31; p=0.019). However, AC repeats of the SRD5A3 gene were not associated with AR protein expression or clinical or pathologic parameters in PCa samples. CONCLUSIONS: These results suggest that the short AC repeats of SRD5A3 polymorphism are associated with an increased risk of PCa. SRD5A3 polymorphism may contribute to a genetic predisposition for PCa.

Expression of aquaporin-3 in ipsilateral rat kidney with unilateral partial ureteral obstruction.

PURPOSE: Aquaporin (AQP), a protein located in the cellular membrane, allows rapid passage of water across the cell membrane. Various AQP subtypes have been associated with ureteral obstruction. In particular, AQP3 has two functions: water and glycerol transport. The aim of this study was to investigate the expression of AQP3 in the ipsilateral rat kidney in unilateral partial ureteral obstruction (UPUO). MATERIALS AND METHODS: Sprague-Dawley rats (n=30, 200-250 g) were divided into two groups. A sham operation was performed in the control group (n=10) and UPUO of the left upper ureter with a silicone tube was induced in the UPUO group (n=20). The left kidney was obtained from both groups 7 days after the operations. The kidney specimens underwent immunofluorescent staining with AQP3 monoclonal antibody, and the density of AQP3 in the tissue was measured with an image analyzer. RESULTS: In the UPUO group, thinning of the epithelial layer and infiltration of inflammatory cells was seen along with the localized expression of AQP3 in the basolateral aspect of the principal collecting duct cells. The mean optical density of AQP3 was significantly lower in the UPUO group than in the control group (100.9±17.5 compared with 131.7±16.9; p<0.001). CONCLUSIONS: These results suggest that a decrease in the expression of AQP3 may be the result of a urinary stasis reaction caused by UPUO in response to local and intrarenal factors. These changes suggest that AQP3 may have a pathophysiological role in UPUO.

Predictive factors that influence treatment outcomes of innovative single incision sling: comparing TVT-Secur to an established transobturator sling for female stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: This study aims to identify independent risk factors for treatment failure of tension-free vaginal tape TVT-Secur (TVT-S) compared to that of the well-established transobturator tape. MATERIALS AND METHODS: Of a total of 175 consecutive patients with urodynamically confirmed stress urinary incontinence (SUI) identified between July 2007 and March 2010, 89 patients underwent TVT-S, and 86 underwent TOT. Cure was defined using the Urogenital Distress Inventory as no urinary leakage during physical activity, coughing, or sneezing as reported by patients during a telephone survey. To identify predictors of treatment failure, multivariable logistic regression models were used, and odds ratios (ORs) were calculated using variables identified during univariate analysis. RESULTS: There were more patients with cystocele ≥ grade 2 in the TVT-S group (p = 0.031); otherwise the groups were well matched. After a median follow-up of 32 months (range, 12-44 months), the overall cure rate was 80.6%; it was 70.8% for those treated with TVT-S and 90.7% for those treated with TOT (p = 0.001). In a multivariate model, previous incontinence surgery (OR 27.1, p = 0.005) and a cystocele ≥ grade 2 (OR 3.0, p = 0.020) were independent risk factors influencing the outcome of TVT-S procedures. For the TOT procedures, detrusor overactivity was an independent risk factor in a multivariate model (OR 8.6, p = 0.033). CONCLUSIONS: TVT-S could be performed for selected patients, but conventional TOT procedures are still superior to the novel TVT-S device.

Neoadjuvant hormonal therapy preceding radical prostatectomy for clinically localized prostate cancer: early postoperative complications and biochemical recurrence.

PURPOSE: The effect of neoadjuvant hormonal therapy (NHT) on radical retropubic prostatectomy (RRP) for prostate cancer is various and remains a controversy for urologists. We conducted this study to comparatively evaluate whether NHT before RRP is indicated and beneficial in the aspects of postoperative complications, positive surgical margin, and biochemical recurrence. MATERIALS AND METHODS: Between September 2006 and December 2009, 69 men were scheduled for RRP as a treatment for clinically localized and locally advanced prostate cancer and were divided into two groups. Group 1 (n=31, 44.9%) was treated with RRP only, and group 2 (n=38, 55.1%) underwent RRP with preoperative NHT. We evaluated clinical parameters, surgical parameters, and the positive margin rate in surgical specimens and the biochemical recurrence rate. RESULTS: There were no statistical differences in age, body mass index (BMI), preoperative biopsy Gleason score, initial serum prostate-specific antigen (PSA) levels, International Prostate Symptom Score (IPSS), or quality of life (QoL) between the two groups (p>0.05). We also observed no differences in the transfusion rate, mean catheterization time, or positive margin rate (p>0.05). However, the mean operative time was significantly higher in the RRP with preoperative NHT group than in the other group (p=0.034). There was no significant difference in the biochemical recurrence rate during the last follow-up according to NHT (p=0.102) or positive surgical margin (p=0.473). CONCLUSIONS: These results suggest that there were no clinical benefits to the administration of NHT before RRP from the viewpoint of biochemical recurrence.

Changes in Urinary Symptoms and Tolerance due to Long-term Ureteral Double-J Stenting.

PURPOSE: Most studies have reported the effects of short-term double-J ureteral stenting on patient symptoms. We reviewed the changes in symptoms and the factors associated with tolerance due to long-term stenting. MATERIALS AND METHODS: We investigated 20 patients (mean age±SD, 58.3±11.8 years). The patients consisted of those with cervical cancer (n=12), retroperitoneal fibrosis (n=5), colon cancer (n=1), rectal cancer (n=1), and endometrial cancer (n=1). A questionnaire that included domains for urinary symptoms and quality of life (QoL) scores for evaluation of urinary symptoms (International Prostate Symptom Score, or IPSS), a 10-cm linear visual analogue scale (VAS) score rated from 0 (no pain) to 10 (unendurable pain) for tolerance, and uroflowmetry were performed at every replacement. RESULTS: Frequency and urgency on the storage symptom score, residual urine sensations, and intermittency on the voiding symptom score were significantly aggravated at the initial stenting (p<0.05), but the sum of the storage symptom score and urgency improved with time (p<0.05). The quality of life score and total IPSS score also changed significantly (p<0.05). However, although the QoL score and the total IPSS score after stenting were not decreased to less than before stenting, the QoL score was significantly decreased at 9 months (p<0.05), and the total IPSS score was significantly decreased at 12 months (p<0.05). CONCLUSIONS: The symptoms were acutely aggravated at first, but the results showed increased tolerance with time. Adaptation of the bladder and desensitization of the patients may be important factors in the increased tolerance.

Factors that predict spontaneous passage of a small distal ureteral stone <5 mm.

PURPOSE: We assessed the role of the unenhanced helical computed tomography (UHCT) for prediction of concurrent ureteral lesions associated with small impacted stones presenting in distal ureter. MATERIALS AND METHODS: From May 2004 to June 2009, we evaluated 30 cases with impacted distal ureteral stones <5 mm. All of the patients were evaluated with unenhancing UHCT, and the secondary signs on UHCT were graded on a scale of 0 to 3. All of the patients were treated by ureteroscopic pneumatic lithotripsy. Ureteral lesions associated with impacted stones were characterized on the basis of the ureteroscopic findings. RESULTS: Ureteroscopic procedures showed that impacted distal ureteral stones <5 mm had concurrent ureteral lesions such as severe mucosal edema, strictures, ureteral polyps, or submucosal stones. Long-term stone impaction and the UHCT findings of a higher degree of the tissue rim sign, hydronephrosis, and perinephric fat stranding were associated with a higher likelihood of the presence of underlying ureteral lesions. CONCLUSIONS: The secondary signs on UHCT such as high degree of tissue rim sign, hydronephrosis, and perinephric fat stranding seem to be useful signs in predicting the presence of concurrent ureteral lesions. In those cases, early intervention might have better outcomes than conservative therapy.

Efficacy and safety of sunitinib on metastatic renal cell carcinoma: a single-institution experience.

PURPOSE: We assessed the efficacy and safety of the tyrosine kinase inhibitor sunitinib in Korean patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Between September 2007 and December 2009, all twenty-one patients who had mRCC with a clear-cell component were retrospectively reviewed. Sunitinib was administered orally at a dose of 50 mg daily until disease progression or intolerance to treatment occurred. The primary end point of this study was the objective tumor response assessed by Response Evaluation Criteria in Solid Tumors (RECIST), and the secondary end points were progression-free survival (PFS) and overall survival (OS) rates as well as assessment of adverse effects. RESULTS: After a median of 17.4 months (range, 5.7-33.1 months) of treatment, 11 patients (52.4%) had an objective response with a complete response in 1 patient (4.8%), and a partial response in 10 patients (47.6%) as the best tumor response. The median PFS was 13.4 months (95% confidence interval [CI], range, 12.3-14.5 months), and the median OS was 28.1 months (95% CI, 21.8-34.4 months). All patients experienced adverse events of some sort, but the studied treatment protocol was well tolerated and most patients experienced reversible grade 1 or 2 toxicities. CONCLUSIONS: Sunitinib was efficacious in the treatment of metastatic clear-cell RCC, and was well tolerated in Korean patients. Although sunitinib treatment-related adverse events such as hand-foot syndrome and facial/generalized edema were observed with a higher incidence than in Western trials, they were mainly mild to moderate, and readily managed.

Successful endourologic management of lower pole moiety ureteropelvic junction obstruction in a partially duplicated collecting system.

We present two cases of symptomatic lower pole moiety ureteropelvic junction obstruction (UPJO) in a partially duplicated collecting system that were successfully treated with minimally invasive endourologic procedures. In the first case, we performed retrograde endopyelotomy with the Acucise(R) ureteral cutting balloon device, and in the latter case, we performed percutaneous nephrolithotomy and antegrade endopyelotomy because of the presence of multiple renal stones. Subsequent intravenous pyelography confirmed marked resolution of the obstruction, and both patients remained asymptomatic during 1 year of follow-up.

Prospective Study Comparing the Suprapubic Arc (Sparc) Procedure and the Transobturator (Monarc) Procedure for Treating Female Stress Urinary Incontinence.

OBJECTIVES: In a comparative trial we evaluated the efficacy and safety of the suprapubic arch (Sparc) and transobturator (Monarc) procedures for the treatment of female stress urinary incontinence (SUI). METHODS: Between November 2003 and May 2004, 46 women with SUI who underwent the Sparc procedure and 42 women who underwent the Monarc procedure were analyzed. The preoperative evaluation included history taking, physical examination, voiding diary, stress and 1-h pad tests and a comprehensive urodynamic examination. Postoperative evaluation included a stress test, 1-h pad test, and uroflowmetry with postvoid residuals. RESULTS: After 1 year of follow up, the rates of cure and satisfaction were 93.5 and 93.0%, respectively, in the Sparc group. The rates of cure and satisfaction were 95.2 and 85.7%, respectively, in the Monarc group. After 2 years of follow up, the rates of cure (93.5 vs 92.9%) and satisfaction (84.8 vs 83.3%) were similar between the two groups. No bladder injury occurred in the Monarc group. Bladder injury occurred in 6.5% (n = 3) of the patients in the Sparc group. Vaginal wall perforation occurred in 4.8% (n = 2) of the patients in the Monarc group (P > 0.05). Late complications included de novo urge symptoms (8.7 vs 11.9%) and voiding dysfunction (10.9 vs 9.5%). CONCLUSIONS: The transobturator Monarc procedure appears to be as efficient and safe as the retropubic Sparc procedure for the treatment of SUI.

Nomograms for prediction of disease recurrence in patients with primary Ta, T1 transitional cell carcinoma of the bladder.

We developed nomograms to predict disease recurrence in patients with Ta, T1 transitional cell carcinoma of the bladder. Thirty-eight training hospitals participated in this retrospective multicenter study. Between 1998 and 2002, a total of 1,587 patients with newly diagnosed non-muscle invasive bladder cancer were enrolled in this study. Patients with prior histories of bladder cancer, non-transitional cell carcinoma, or a follow-up duration of less than 12 months were excluded. With univariate and multivariate logistic regression analyses, we constructed nomograms to predict disease recurrence, and internal validation was performed using statistical techniques. Three-year and five-year recurrence-free rates were 64.3% and 55.3%, respectively. Multivariate analysis revealed that age (hazard ratio [HR]=1.437, p<0.001), tumor size (HR=1.328, p=0.001), multiplicity (HR=1.505, p<0.001), tumor grade (HR=1.347, p=0.007), concomitant carcinoma in situ (HR=1.611, p=0.007), and intravesical therapy (HR=0.681, p<0.001) were independent predictors for disease recurrence. Based on these prognostic factors, nomograms for the prediction of disease recurrence were developed. These nomograms can be used to predict the probability of disease recurrence in patients with newly diagnosed Ta, T1 transitional cell carcinoma of the bladder. They may be useful for patient counseling, clinical trial design, and patient follow-up planning.

Efficacy of low-dose tamsulosin on lower urinary tract symptoms suggestive of benign prostatic hyperplasia : a nonblind multicentre korean study.

OBJECTIVE: To evaluate the efficacy and tolerability of tamsulosin 0.2mg once daily in Korean patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH), who were treated for up to 1 year. MATERIALS AND METHODS: Of the 211 patients from six urology outpatient centres who participated in this investigation, 146 patients were evaluable. Tamsulosin 0.2 mg/day was administered orally in a nonblind design for a 1-year period. The primary efficacy parameters were improvement in the total, obstructive and irritative International Prostate Symptom Score (IPSS), measured at baseline and at weeks 12, 24, 36 and 52, and in the maximal urinary flow rate (Qmax) measured at baseline and at weeks 24 and 52. The secondary efficacy parameters were a decrease of >/=30% in IPSS, and an increase in Qmax of >/=30% from baseline. Changes in parameters between baseline and 52 weeks were assessed using Student's paired t-test. RESULTS: Statistically significant, gradual improvements in all efficacy parameters were observed over the 1-year period. Tamsulosin 0.2 mg/day resulted in a mean reduction of 41.1% in total IPSS (p < 0.001) and a mean increase of 4.56 mL/sec in Qmax at 52 weeks (p < 0.001). Tamsulosin was well tolerated; adverse events occurred in 6.2% of patients and there were no withdrawals as a result of adverse events. There were no significant changes in blood pressure or pulse rate during the study. CONCLUSIONS: One-year treatment with tamsulosin 0.2 mg/day in Korean patients with suspected BPH was well tolerated and effective in improving LUTS and urinary flow. The effect on symptoms was apparent after 12 weeks of treatment, and symptom improvement was observed for up to 1 year.