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1.  Treatment of upper urinary tract stones with extracorporeal shock wave lithotripsy (ESWL) Sonolith vision 
BMC Urology  2011;11:26.
Background
The aim was to retrospectively assess the results of treatment of upper urinary tract stones with the Sonolith vision manufactured by EDAP, and purchased in 2004.
Methods
The subjects were 226 Japanese patients who underwent extracorporeal shock wave lithotripsy (ESWL) alone as an initial treatment and could be followed up for at least 3 months, selected from 277 candidate patients who underwent this therapy between 2004 and 2006. Treatment effect was evaluated by kidney, ureter, and bladder X-ray or renal ultrasonography at 1 and 3 months after treatment. A stone-free status or status of stone fragmentation to 4 mm or smaller was considered to indicate effective treatment.
Results
At 3 months after treatment, the stone-free rate was 69.4% and the efficacy rate was 77.4% for renal stones, while these rates were 91.5 and 93.3%, respectively for ureteral stones. Assessment of treatment effect classified by the location of stones revealed a stone-free rate of 94.6% and an efficacy rate of 94.6% for lower ureteral stones (4.0 mm or smaller, 1 subject; 4.1-10.0 mm, 31 subjects; 10.1-20.0 mm, 5 subjects: number of treatment sessions, 1 or 2 sessions [mean: 1.03 sessions]). Complications of this therapy included renal subcapsular hematoma and pyelonephritis in 1 case each.
Conclusions
ESWL with the Sonolith vision manufactured by EDAP produced a treatment effect equivalent to those achieved with other models of ESWL equipment. ESWL seems to be an effective first-line treatment also in patients who have lower ureteral stones 10 mm or larger but do not wish to undergo TUL, if measures such as suitable positioning of the patient during treatment are taken.
doi:10.1186/1471-2490-11-26
PMCID: PMC3265410  PMID: 22152040
2.  Choroidal metastases in testicular choriocarcinoma, successful treatment with chemo- and radiotherapy: a case report 
BMC Urology  2011;11:24.
Background
Choriocarcinoma is a very rare cause of ocular metastasis. Only 18 male patients have been reported on, 4 of whom survived, but with significant loss of vision.
Case presentation
A 26-year-old Caucasian man, suffering from testicular choriocarcinoma with pulmonary, cerebral, renal, hepatic and osseous metastases, underwent left radical orchiectomy. While being treated with chemotherapy, he presented with loss of vision in the left eye. Ophthalmoscopy revealed bilateral non-pigmented, hemorrhagic choroidal tumours, compatible with secondary lesions. Continued chemotherapy and stereotactic radiotherapy of the skull and spine lead to full remission with excellent vision, after more than 4 years of follow up.
Conclusion
Testicular choriocarcinoma is an exceptional cause of choroidal metastasis, potentially asymptomatic and with specific clinical features. Radiotherapy can complement radical orchiectomy and chemotherapy, to achieve full remission and maintain good vision.
doi:10.1186/1471-2490-11-24
PMCID: PMC3252243  PMID: 22151977
3.  Predictors and outcome of surgical repair of obstetric fistula at a regional referral hospital, Mbarara, western Uganda 
BMC Urology  2011;11:23.
Background
Obstetric fistula although virtually eliminated in high income countries, still remains a prevalent and debilitating condition in many parts of the developing world. It occurs in areas where access to care at childbirth is limited, or of poor quality and where few hospitals offer the necessary corrective surgery.
Methods
This was a prospective observational study where all women who attended Mbarara Regional Referral Hospital in western Uganda with obstetric fistula during the study period were assessed pre-operatively for social demographics, fistula characteristics, classification and outcomes after surgery. Assessment for fistula closure and stress incontinence after surgery was done using a dye test before discharge
Results
Of the 77 women who were recruited in this study, 60 (77.9%) had successful closure of their fistulae. Unsuccessful fistula closure was significantly associated with large fistula size (Odds Ratio 6 95% Confidential interval 1.46-24.63), circumferential fistulae (Odds ratio 9.33 95% Confidential interval 2.23-39.12) and moderate to severe vaginal scarring (Odds ratio 12.24 95% Confidential interval 1.52-98.30). Vaginal scarring was the only factor independently associated with unsuccessful fistula repair (Odds ratio 10 95% confidential interval 1.12-100.57). Residual stress incontinence after successful fistula closure was associated with type IIb fistulae (Odds ratio 5.56 95% Confidential interval 1.34-23.02), circumferential fistulae (Odds ratio 10.5 95% Confidential interval 1.39-79.13) and previous unsuccessful fistula repair (Odds ratio 4.8 95% Confidential interval 1.27-18.11). Independent predictors for residual stress incontinence after successful fistula closure were urethral involvement (Odds Ratio 4.024 95% Confidential interval 2.77-5.83) and previous unsuccessful fistula repair (Odds ratio 38.69 95% Confidential interval 2.13-703.88).
Conclusions
This study demonstrated that large fistula size, circumferential fistulae and marked vaginal scarring are predictors for unsuccessful fistula repair while predictors for residual stress incontinence after successful fistula closure were urethral involvement, circumferential fistulae and previous unsuccessful fistula repair.
doi:10.1186/1471-2490-11-23
PMCID: PMC3252285  PMID: 22151960
4.  Caveolin 1 protein expression in renal cell carcinoma predicts survival 
BMC Urology  2011;11:25.
Background
Caveolae play a significant role in disease phenotypes such as cancer, diabetes, bladder dysfunction, and muscular dystrophy. The aim of this study was to elucidate the caveolin-1 (CAV1) protein expression in renal cell cancer (RCC) and to determine its potential prognostic relevance.
Methods
289 clear cell RCC tissue specimens were collected from patients undergoing surgery for renal tumors. Both cytoplasmic and membranous CAV1 expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for 169 evaluable patients with a median follow up of 80.5 months (interquartile range (IQR), 24.5 - 131.7 months).
Results
A high CAV1 expression in the tumor cell cytoplasm was significantly associated with male sex (p = 0.04), a positive nodal status (p = 0.04), and poor tumor differentiation (p = 0.04). In contrast, a higher than average (i.e. > median) CAV1 expression in tumor cell membranes was only linked to male sex (p = 0.03). Kaplan-Meier analysis disclosed significant differences in 5-year overall (51.4 vs. 75.2%, p = 0.001) and tumor specific survival (55.3 vs. 80.1%, p = 0.001) for patients with higher and lower than average cytoplasmic CAV1 expression levels, respectively. Applying multivariable Cox regression analysis a high CAV1 protein expression level in the tumor cell cytoplasm could be identified as an independent poor prognostic marker of both overall (p = 0.02) and tumor specific survival (p = 0.03) in clear cell RCC patients.
Conclusion
Over expression of caveolin-1 in the tumour cell cytoplasm predicts a poor prognosis of patients with clear cell RCC. CAV1 is likely to be a useful prognostic marker and may play an important role in tumour progression. Therefore, our data encourage further investigations to enlighten the role of CAV1 and its function as diagnostic and prognostic marker in serum and/or urine of RCC patients.
doi:10.1186/1471-2490-11-25
PMCID: PMC3266190  PMID: 22152020
5.  ROS generation via NOX4 and its utility in the cytological diagnosis of urothelial carcinoma of the urinary bladder 
BMC Urology  2011;11:22.
Background
Reactive oxygen species (ROS) production via NADPH oxidase (NOX) contributes to various types of cancer progression. In the present research, we examined the pathobiological role of NADPH oxidase (NOX)4-mediated generation of reactive oxygen species (ROS) in urothelial carcinoma (UC) of the urinary bladder, and demonstrated the utility of ROS labeling in urine cytology.
Methods
NOX4 gene was silenced in vivo and in vitro by NOX4 siRNA transfection with or without atlocollagen. Cell cycle and measurement of ROS were analyzed by flowcytometry. Orthotopic implantation animal model was used in vivo experiment. NOX4 expression in urothelial carcinoma cells was observed by immunohistochemical analysis using surgical specimens of human bladder cancer. Urine cytology was performed after treatment with ROS detection reagents in addition to Papanicolaou staining.
Results
NOX4 was overexpressed in several UC cell lines and the NOX inhibitor, diphenylene iodonium reduced intracellular ROS and induced p16-dependent cell cycle arrest at the G1 phase. Moreover, silencing of NOX4 by siRNA significantly reduced cancer cell growth in vivo as assessed in an orthotopic mouse model. Immunohistochemistry demonstrated high expression of NOX4 in low grade/non-invasive and high grade/invasive UC including precancerous lesions such as dysplasia but not in normal urothelium. Then, we assessed the usefulness of cytological analysis of ROS producing cells in urine (ROS-C). Urine samples obtained from UC cases and normal controls were treated with fluorescent reagents labeling the hydrogen peroxide/superoxide anion and cytological atypia of ROS positive cells were analyzed. As a result, the sensitivity for detection of low grade, non-invasive UC was greatly increased (35% in conventional cytology (C-C) vs. 75% in ROS-C), and the specificity was 95%. Through ROS-C, we observed robust improvement in the accuracy of follow-up urine cytology for cases with previously diagnosed UC, especially in those with low grade/non-invasive cancer recurrence (0% in C-C vs. 64% in ROS-C).
Conclusions
This is the first report demonstrating that ROS generation through NOX4 contributes to an early step of urothelial carcinogenesis and cancer cell survival. In addition, cytology using ROS labeling could be a useful diagnostic tool in human bladder cancer.
doi:10.1186/1471-2490-11-22
PMCID: PMC3215170  PMID: 22032647
6.  Overall and worst gleason scores are equally good predictors of prostate cancer progression 
BMC Urology  2011;11:21.
Background
Gleason scoring has experienced several modifications during the past decade. So far, only one study has compared the prognostic abilities of worst (WGS) and overall (OGS) modified Gleason scores after the ISUP 2005 conference. Prostatic needle biopsies are individually paraffin-embedded in 57% of European pathology laboratories, whereas the rest of laboratories embed multiple (2 - 6) biopsies per one paraffin-block. Differences in the processing method can have a far-reaching effect, because reporting of the Gleason score (GS) is different for individually embedded and pooled biopsies, and GS is one of the most important factors when selecting treatment for patients.
Methods
The study material consisted of needle biopsies from 236 prostate cancer patients that were endocrine-treated in 1999-2003. Biopsies from left side and right side were embedded separately. Haematoxylin-eosin-stained slides were scanned and analyzed on web-based virtual microscopy. Worst and overall Gleason scores were assessed according to the modified Gleason score schema after analyzing each biopsy separately. The compound Gleason scores (CGS) were obtained from the original pathology reports. Two different grade groupings were used: GS 6 or less vs. 7 vs. 8 or above; and GS 7(3 + 4) or less vs. 7(4 + 3) and 8 vs. 9-10. The prognostic ability of the three scoring methods to predict biochemical progression was compared with Kaplan-Meier survival analysis and univariate and multivariate Cox regression analyses.
Results
The median follow-up time of the patients was 64.5 months (range 0-118). The modified GS criteria led to upgrading of the Gleason sums compared to the original CGS from the pathology reports 1999-2003 (mean 7.0 for CGS, 7.5 for OGS, 7.6 for WGS). In 43 cases WGS was > OGS. In a univariate analysis the relative risks were 2.1 (95%-confidence interval 1.8-2.4) for CGS, 2.5 (2.1-2.8) for OGS, and 2.6 (2.2-2.9) for WGS. In a multivariate analysis, OGS was the only independent prognostic factor.
Conclusions
All of the three Gleason scoring methods are strong predictors of biochemical recurrence. The use of modified Gleason scoring leads to upgrading of GS, but also improves the prognostic value of the scoring. No significant prognostic differences between OGS and WGS could be shown, which may relate to the apparent narrowing of the GS scale from 2-10 to 5-10 due to the recent modifications.
doi:10.1186/1471-2490-11-21
PMCID: PMC3193164  PMID: 21978318
7.  A case of squamous cell carcinoma arising from a suprapubic cystostomy tract 
BMC Urology  2011;11:20.
Background
Patients with spinal cord injury and a chronic indwelling urinary catheter are known to have an increased risk of bladder malignancy. However, squamous cell carcinoma (SCC) of the epidermis around a suprapubic cystostomy is relatively rare. Here, we report a case of lower abdominal SCC arising from the suprapubic cystostomy tract.
Case presentation
A 58-year-old man with a complete spinal cord injury was referred to our hospital with a chief complaint of an abdominal mass. Abdominal enhanced computed tomography (CT) showed a 7-cm mass surrounding the suprapubic cystostomy and bilateral inguinal and para-aortic lymph nodes metastasis. Histopathological examination of percutaneous biopsy specimens was performed. The diagnosis was stage IV (cT4N1M1) epidermal SCC, which was treated with palliative external radiation therapy.
Conclusion
The SCC in this case was thought to arise from mechanical stimulus of the suprapubic cystostomy. Physicians and patients should pay careful attention to any signs of neoplasms with long-term indwelling catheters, such as skin changes around the suprapubic cystostomy site. This case presentation is only the fourth report of SCC arising from the suprapubic cystostomy tract in the literature. In cases of unresectable tumors and contraindications to chemotherapy, palliative radiotherapy may lead to disease remission and symptom relief.
doi:10.1186/1471-2490-11-20
PMCID: PMC3198751  PMID: 21967681
8.  Phosphatidylinositol 3'-kinase, mTOR, and Glycogen synthase kinase-3β mediated regulation of p21 in human urothelial carcinoma cells 
BMC Urology  2011;11:19.
Background
The PTEN/Phosphatidylinositol 3'-kinase (PI3-kinase) growth factor signaling pathway plays a critical role in epithelial tumor development in a multitude of tissue types. Deletion of the Pten tumor suppressor gene in murine urothelial cells in vivo results in upregulation of cyclin-dependent kinase inhibitor p21. We have previously shown in mice that p21 expression blocks an increase in urothelial cell proliferation due to Pten deletion. In this study, we utilized human urothelial carcinoma cells UMUC-3 and UMUC-14 to identify the signaling pathways downstream of PI3-kinase that regulate p21.
Methods
Cells were treated with a combination of PI3-kinase stimulating growth factors and kinase inhibitors, or transfected with exogenous genes in order to identify the signaling events that are necessary for p21 induction. Mice with conditional deletion of Pten in bladder urothelium were also examined for evidence of PI3-kinase pathway signaling events that affect p21 expression.
Results
When cells were treated with PI3-kinase activating growth factors EGF or PDGF, we found that p21 levels increased, in a manner similar to that observed in mice. We used the inhibitors LY294002, Akti-1/2, and rapamycin, to show that p21 induction is dependent upon PI3-kinase and AKT activity, and partially dependent on mTOR. We treated the cells with proteasome inhibitor MG-132 and found that p21 may be degraded in the proteasome to regulate protein levels. Importantly, our findings show that GSK-3β plays a role in diminishing p21 levels in cells. Treatment of cells with the GSK-3β inhibitor SB-216763 increased p21 levels, while exogenous expression of GSK-3β caused a decrease in p21, indicating that GSK-3β actively reduces p21 levels. We found that a combined treatment of LY294002 and SB-216763 improved the cytotoxic effect against UMUC-3 and UMUC-14 carcinoma cells over LY294002 alone, suggesting potential therapeutic uses for GSK-3β inhibitors. Immunohistochemical staining in bladders from wild-type and Pten-deleted mice indicated that GSK-3β inhibitory phosphorylation increases when Pten is deleted.
Conclusion
PI3-kinase and AKT cause an upregulation of p21 by suppressing GSK-3β activity and activating mTOR in both cultured human urothelial carcinoma cells and mouse urothelial cells in vivo.
doi:10.1186/1471-2490-11-19
PMCID: PMC3173386  PMID: 21864408
9.  Effects of acute adult and early-in-life bladder inflammation on bladder neuropeptides in adult female rats 
BMC Urology  2011;11:18.
Background
The purpose of the present study was to determine how acute adult and/or prior early-in life (EIL; P14-P16) exposure to bladder inflammation affects bladder content of calcitonin gene related peptide (CGRP) and substance P (SP). Estrous cycle influences were also studied in the adult-treatment conditions.
Methods
In Experiment 1, intravesical zymosan or isoflurane anesthesia alone was administered to adult female rats. Bladders and serum were collected 24 hours later during each phase of the estrous cycle. In Experiment 2, zymosan or anesthesia alone was administered EIL and as adults, with bladder tissue collection 24 h later.
Results
In general, Experiment 1 showed that bladder content of both CGRP and SP was increased by inflammation. This effect was significant when data were collapsed across all phases of the estrous cycle, but was only significant during proestrus when individual comparisons were made during each phase of estrous. Also, adult bladder inflammation significantly reduced estradiol levels. In Experiment 2, bladder content of CGRP and SP was significantly increased in rats receiving EIL and/or adult inflammation. Bladder weights were also significantly increased by inflammation.
Conclusions
These data indicate that bladder CGRP and SP are maximally increased during the proestrus phase of the estrous cycle in inflamed adult female rats. EIL exposure to bladder inflammation alone can also produce an increase in CGRP and SP lasting into adulthood. Therefore, EIL experience with bladder inflammation may predispose an organism to experience a painful bladder disorder as an adult by increasing primary afferent content of CGRP and/or SP.
doi:10.1186/1471-2490-11-18
PMCID: PMC3171712  PMID: 21843346
10.  Clinical significance of subepithelial growth patterns in non-muscle invasive bladder cancer 
BMC Urology  2011;11:17.
Background
We evaluated the clinical significance and prognostic value of histopathological features of bladder cancer, such as subepithelial growth patterns and tumor growth pattern at the invasion front.
Methods
In total, 130 patients newly diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection between 1998 and 2009 were enrolled. Subepithelial growth patterns consisting of endophytic growth pattern (EGP) and von Brunn's nest involvement (VBNI) were investigated using hematoxylin and eosin-stained slides, and their frequency of occurrence, prognostic value, and correlation with other clinicopathological features was evaluated.
Results
EGP and VBNI were found in 40 (30.8%) and 5 (3.9%) of the 130 cases, respectively. Of the 26 pT1 tumors, the growth pattern at the invasion front was trabecular in 17 (65.4%) and infiltrative in 9 (34.6%). Although 8 (47.1%) of 17 trabecular tumors coexisted with EGP, no cases with infiltrative tumors had EGP (p = 0.023). VBNI correlated with high tumor grades (p = 0.006) and lymphovascular involvement (p = 0.026). The multivariate Cox proportional hazards analysis revealed that tumor diameter less than 3 cm (p = 0.04) and intravesical bacillus Calmette-Guérin therapy (p = 0.004) were independent favorable prognostic factors for recurrence-free survival, whereas tumor stage was an independent poor prognostic factor for disease progression (p = 0.006).
Conclusions
Subepithelial growth patterns were not a significant prognostic factor in this study. Additionally, no tumors with an infiltrative growth pattern coexisted with EGP, suggesting that determining the presence of EGP might be helpful for managing non-muscle invasive bladder cancers.
doi:10.1186/1471-2490-11-17
PMCID: PMC3167754  PMID: 21816111
bladder cancer; endophytic growth pattern; prognostic factor; infiltrative pattern
11.  Renal cell carcinoma with a tumor thrombus in the ureter: a case report 
BMC Urology  2011;11:16.
Background
Renal cell carcinoma (RCCs) is the most common malignancy of the kidney. When RCC progresses, it is known to form tumor thrombus in the renal vein and/or inferior vena cava. However, RCC does not normally form tumor thrombus in the ureter or renal pelvis.
Case presentation
A 43-year-old man presented to our department for the treatment of a renal tumor with asymptomatic gross hematuria. In a dynamic CT study, contrast enhancement revealed a tumor suspected to be RCC, but atypical finding as a tumor thrombus that filled the renal pelvis and the whole ureter was also observed. Nephroureterectomy was performed, and the tumor was diagnosed histopathologically as RCC.
Conclusion
We report here a very rare case of RCC with a tumor thrombus in the whole ureter.
doi:10.1186/1471-2490-11-16
PMCID: PMC3161958  PMID: 21806792
12.  A 6-month depot formulation of leuprolide acetate is safe and effective in daily clinical practice: a non-interventional prospective study in 1273 patients 
BMC Urology  2011;11:15.
Background
Testosterone stimulates growth in many prostate tumours. The established GnRH analogue leuprolide acetate is incorporated in a novel biodegradable polymer matrix (Atrigel® delivery system), that can be administered to reduce testosterone levels in men with advanced hormone-dependent prostate cancer. This novel formulation is available as a 1-, 3- and most recently 6-month depot (Eligard® 45 mg). The latter was shown to lower and maintain safe and effective serum testosterone suppression in a clinical study.
Methods
A non-interventional study to confirm the efficacy and safety of 6-monthly leuprolide acetate (Eligard® 45 mg) in routine urological practice was performed in Germany. Data were obtained from 1273 patients under the care of 634 urologists, and were analysed descriptively. Concentrations of PSA and serum testosterone were documented at the baseline visit and at 6 and 12 months following 6-monthly leuprolide acetate. The participating physicians were also asked to assess the efficacy, tolerabilty and handling of 6-monthly leuprolide acetate.
Results
Serum concentrations of PSA and testosterone were decreased substantially within 6 months of initial 6-monthly leuprolide acetate administration. At 12 months, median reductions of 96% (to 0.5 ng/ml) in PSA, and 90% (to 8.9 ng/dl) in serum testosterone, were observed. Further PSA and serum testosterone decreases were also observed in a subpopulation of patients who switched to 6-monthly leuprolide acetate from other GnRH analogues. Physicians rated 6-monthly leuprolide acetate as easy to use, and patients reported good tolerability. Adverse events occurred in 9% of patients; the majority were not serious. In particular, low rates of hot flushes were reported.
Conclusions
This non-interventional study showed that the reliable reduction of PSA and testosterone levels demonstrated in previous clinical studies of twice-yearly leuprolide acetate can also be achieved in routine clinical practice. This study also confirmed good tolerability of 6-monthly leuprolide acetate in routine clinical use and received positive appraisal from physicians.
doi:10.1186/1471-2490-11-15
PMCID: PMC3161957  PMID: 21801354
13.  Bilateral ureteropelvic disruption following blunt abdominal trauma: Case report 
BMC Urology  2011;11:14.
Background
Ureteral injury occurs in less than 1% of blunt abdominal trauma cases, partly because the ureters are relatively well protected in the retroperitoneum. Bilateral ureteral injury is extremely rare, with only 10 previously reported cases. Diagnosis may be delayed if ureteric injury is not suspected, and delay of 36 hours or longer has been observed in more than 50% of patients with ureteric injury following abdominal trauma, leading to increased morbidity.
Case presentation
A 29-year-old man was involved in a highway motor vehicle collision and was ejected from the front passenger seat even though wearing a seatbelt. He was in a preshock state at the scene of the accident. An intravenous line and left thoracic drain were inserted, and he was transported to our hospital by helicopter. Whole-body, contrast-enhanced computed tomography (CT) scan showed left diaphragmatic disruption, splenic injury, and a grade I injury to the left kidney with a retroperitoneal haematoma. He underwent emergency laparotomy. The left diaphragmatic and splenic injuries were repaired. Although a retroperitoneal haematoma was observed, his renal injury was treated conservatively because the haematoma was not expanding. In the intensive care unit, the patient's haemodynamic state was stable, but there was no urinary output for 9 hours after surgery. Anuresis prompted a review of the abdominal x-ray which had been performed after the contrast-enhanced CT. Leakage of contrast material from the ureteropelvic junctions was detected, and review of the repeat CT scan revealed contrast retention in the perirenal retroperitoneum bilaterally. He underwent cystoscopy and bilateral retrograde pyelography, which showed bilateral complete ureteral disruption, preventing placement of ureteral stents. Diagnostic laparotomy revealed complete disruption of the ureteropelvic junctions bilaterally. Double-J ureteral stents were placed bilaterally and ureteropelvic anastomoses were performed. The patient's postoperative progress was satisfactory and he was discharged on the 23rd day.
Conclusion
Diagnosis of ureteral injury was delayed, although delayed phase contrast-enhanced CT and abdominal x-rays performed after CT revealed the diagnosis early. Prompt detection and early repair prevented permanent renal damage and the necessity for nephrectomy.
doi:10.1186/1471-2490-11-14
PMCID: PMC3161023  PMID: 21733189
14.  Efficacy of tension-free vaginal tape compared with transobturator tape in the treatment of stress urinary incontinence in women: analysis of learning curve, perioperative changes of voiding function 
BMC Urology  2011;11:13.
Background
In this study, by comparing TVT surgery and TOT surgery for stress urinary incontinence in women, the characteristics and learning curves of both operative methods were studied.
Methods
A total of 83 women with stress urinary incontinence treated with tension-free vaginal tape (TVT) (n = 38) or transobturator tape (TOT) (n = 45) at Saiseikai Central Hospital between April 2004 and September 2009 were included. We compare the outcomes and learning curves between TVT surgery and TOT surgery. In statistical analysis, Student's t test, Fisher's exact test, and Mann-Whitney's U test were used.
Results
The surgical durations were 37.4 ± 15.7 minutes with TVT surgery and 31.0 ± 8.3 minutes with TOT surgery. A longer period of time was required for TVT surgery (p = 0.025). The residual urine at post-operative day 1 was higher in TVT surgery (25.9 ± 44.2 ml) than in TOT surgery (10.6 ± 19.2 ml) (p = 0.0452). The surgical duration of TVT surgery was shortened after the operator had performed 15 operations (p = 0.019).
Conclusions
In comparison of TVT surgery and TOT surgery, the surgical duration of TVT surgery was longer and the residual urine of TVT surgery was higher at post-operative day 1. Surgical experience could shorten the duration of TVT surgery.
doi:10.1186/1471-2490-11-13
PMCID: PMC3141808  PMID: 21726448
Stress urinary incontinence; TVT surgery; TOT surgery
15.  Immunohistochemical analysis of ezrin-radixin-moesin-binding phosphoprotein 50 in prostatic adenocarcinoma 
BMC Urology  2011;11:12.
Background
Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is an adapter protein which has been shown to play an active role in a wide variety of cellular processes, including interactions with proteins related to both tumor suppression and oncogenesis. Here we use immunohistochemistry to evaluate EBP50's expression in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets).
Methods
Tissue microarrays were immunohistochemically stained for EBP50, with the staining intensities quantified using automated image analysis software. The data were statistically analyzed using one-way ANOVA with subsequent Tukey tests for multiple comparisons. Eleven cases of NDP, 37 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 103 cases of PCa, and 36 cases of Mets were analyzed in the microarrays.
Results
Specimens of PCa and Mets had the lowest absolute staining for EBP50. Mets staining was significantly lower than NDP (p = 0.027), BPH (p = 0.012), NAC (p < 0.001), HGPIN (p < 0.001), and PCa (p = 0.006). Additionally, HGPIN staining was significantly higher than NAC (p < 0.009) and PCa (p < 0.001).
Conclusions
To our knowledge, this represents the first study comparing the immunohistochemical profiles of EBP50 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC and suggests that EBP50 expression is decreased in Mets. Given that PCa also had significantly higher expression than Mets, future studies are warranted to assess EBP50's potential as a prognostic biomarker for prostate cancer.
doi:10.1186/1471-2490-11-12
PMCID: PMC3132203  PMID: 21672215
16.  Hyperbaric oxygen therapy for painful bladder syndrome/interstitial cystitis resistant to conventional treatments: long-term results of a case series in Japan 
BMC Urology  2011;11:11.
Background
There is no confirmed strategy for treating painful bladder syndrome/interstitial cystitis (PBS/IC) with unclear etiology. Therefore, a pilot study was carried out to evaluate the efficacy and safety of hyperbaric oxygen (HBO) therapy in treatment-resistant PBS/IC patients.
Methods
HBO treatment (2.0 ATA for 60 minutes/day × 5 days/week for 2 or 4 weeks) was performed on 11 patients with severe symptoms that had not been improved by previous therapy regimens between December 2004 and July 2009.
Results
Seven of the 11 patients demonstrated persistent improvement in symptoms during the 12 months after HBO treatment. These responders demonstrated a decrease in the pelvic pain scale and urgency scale from 7.7 ± 1.0 and, 6.6 ± 0.9 to 3.4 ± 2.5 and 4.3 ± 2.4 after 12 months, respectively (p < 0.05). The total score of the interstitial cystitis symptom index and 24-hour urinary frequency demonstrated a significant sustained decrease from the baseline. Two responders, who received an additional course of HBO 12 and 13 months after initial treatment, respectively, did not suffer impairment for more than two years. There was one case of transient eustachian tube dysfunction and three cases of reversible exudative otitis media as a consequence of HBO treatment.
Conclusions
HBO is a potent treatment for PBS/IC patients resistant to conventional therapy. It was well tolerated and provided maintained amelioration of pain, urgency and urinary frequency for at least 12 months.
doi:10.1186/1471-2490-11-11
PMCID: PMC3116481  PMID: 21609485
17.  Urethral catheters: can we reduce use? 
BMC Urology  2011;11:10.
Background
Indwelling urinary catheters are the main cause of healthcare-associated urinary tract infections. It can be expected that reduction of the use of urinary catheters will lead to decreased numbers of urinary tract infection.
Methods
The efficacy of an intervention programme to improve adherence to recommendations to reduce the use of urethral catheters was studied in a before-after comparison in ten Dutch hospitals. The programme detected barriers and facilitators and each individual facility was supported with developing their own intervention strategy. Outcome was evaluated by the prevalence of catheters, alternatives such as diapers, numbers of urinary tract infections, the percentage of correct indications and the duration of catheterization. The costs of the implementation as well as the catheterization were evaluated.
Results
Of a population of 16,495 hospitalized patients 3335 patients of whom 2943 were evaluable for the study, had a urethral catheter. The prevalence of urethral catheters decreased insignificantly in neurology (OR 0.93; 95% CI 0.77 - 1.13) and internal medicine wards (OR 0.97; 95% CI 0.83 - 1.13), decreased significantly in surgical wards (OR 0.84; 95% CI 0.75 - 0.96), but increased significantly in intensive care (IC) and coronary care (CC) units (OR 1.48; 95% CI 1.01 - 2.17). The use of alternatives was limited and remained so after the intervention. Duration of catheterization decreased insignificantly in IC/CC units (ratio after/before 0.95; 95% CI 0.78 - 1.16) and neurology (ratio 0.97; 95% CI 0.80 - 1.18) and significantly in internal medicine (ratio 0.81; 95% CI 0.69 - 0.96) and surgery wards (ratio 0.80; 95% CI 0.71 - 0.90). The percentage of correct indications on the day of inclusion increased from 50 to 67% (p < 0.0001). The prevalence of urinary tract infections in catheterized patients did not change. The mean cost saved per 100 patients was € 537.
Conclusion
Targeted implementation of recommendations from an existing guideline can lead to better adherence and cost savings. Especially, hospitals which use a lot of urethral catheters or where catheterization is prolonged, can expect important improvements.
doi:10.1186/1471-2490-11-10
PMCID: PMC3121730  PMID: 21605403
18.  Cost-effectiveness analysis of antimuscarinics in the treatment of patients with overactive bladder in Spain: A decision-tree model 
BMC Urology  2011;11:9.
Background
Fesoterodine, a new once daily antimuscarinic, has proven to be an effective, safe, and well-tolerated treatment in patients with overactive bladder (OAB). To date, no analysis has evaluated the economic costs and benefits associated with fesoterodine, compared to antimuscarinics in Spain. The purpose of this analysis was to assess the economic value of OAB treatment with fesoterodine relative to extended release tolterodine and solifenacin, from the societal perspective.
Methods
The economic model was based on data from two 12-week, randomized, double-blind, and multicenter trials comparing fesoterodine and tolterodine extended released (ER). Treatment response rates for solifenacin were extracted from the published literature. Discontinuation and efficacy were based on the results of a 12-week multinational randomized clinical trial extrapolated to 52 weeks. Changes in health related quality of life were assessed with the King's Health Questionnaire, which was transformed into preference-based utility values. Medical costs included (expressed in € 2010) were antimuscarinics, physician visits, laboratory tests, incontinence pads and the costs of OAB-related comorbidities, fractures, skin infections, urinary tract infections, depression, and nursing home admissions associated with incontinence. Time lost from work was also considered. Univariate sensitivity analyses were also performed.
Results
At week 12, continents accounted for 50.6%, 40.6% and 47.2% of patients in the fesoterodine, tolterodine, and solifenacin groups, respectively. By week 52, the projected proportions of patients remaining on therapy were 33.1%, 26.5% and 30.8%, respectively. The projected quality- adjusted life years (QALY) gain (compared to baseline) over the 52-week simulation period were 0.01014, 0.00846 and 0.00957, respectively. The overall treatment cost was estimated at €1,937, €2,089 and €1,960 for fesoterodine, tolterodine and solifenacin, respectively. Therefore, treatment with fesoterodine resulted in similar overall costs and greater QALY gain than treatment with either tolterodine or solifenacin. Sensitivity analysis showed that these results were robust to all changes performed.
Conclusions
The results of this economic analysis suggest that fesoterodine is a cost-effective alternative to tolterodine and solifenacin for the treatment of patients with OAB in Spain. Fesoterodine provides additional health benefits while maintain a similar level of costs being a cost-effective treatment strategy from a societal perspective.
doi:10.1186/1471-2490-11-9
PMCID: PMC3126790  PMID: 21599928
19.  Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival 
BMC Urology  2011;11:8.
Background
Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated in vitro and in vivo.
Methods
COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown in vivo. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases) were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells.
Results
Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK) 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA), resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes.
Conclusions
COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.
doi:10.1186/1471-2490-11-8
PMCID: PMC3111585  PMID: 21592330
cyclooxygenase 2; urothelial carcinoma; casein kinase 2α; Akt
20.  Duration of androgen deprivation therapy with maximum androgen blockade for localized prostate cancer 
BMC Urology  2011;11:7.
Background
Primary androgen deprivation therapy (ADT) is a treatment option not only for advanced but also for localized prostate cancer. However, the appropriate duration for primary ADT for localized prostate cancer has not been defined and few studies have addressed this issue. In this study, we aimed to determine the appropriate duration of ADT for localized prostate cancer.
Methods
Sixty-eight consecutive patients with localized prostate cancer who underwent a prostatectomy following neoadjuvant ADT were retrospectively reviewed. Factors associated with pT0, which is regarded as serious cancer cell damage or elimination, were investigated.
Results
Of the 68 males, 24 (35.3%) were classified as pT0. The median duration of neoadjuvant ADT in the pT0 and non-pT0 groups was 9 months and 7.5 months, respectively (p = 0.022). The duration of neoadjuvant ADT from when PSA reached < 0.2 ng/ml to surgery was longer in the pT0 group than that in the non-pT0 group (median 5 months against 3 months, p = 0.011). pT0 was achieved in 5 of 6 patients (83.3%) who received ADT for ≥10 months after PSA reached < 0.2 ng/ml. No other clinical characteristics predicted conversion to pT0.
Conclusions
Continuous ADT for ≥10 months after PSA reached < 0.2 ng/ml induced serious prostate cancer cell damage in most patients (> 80%) and may be sufficient to treat localized prostate cancer.
doi:10.1186/1471-2490-11-7
PMCID: PMC3116482  PMID: 21569574
21.  The primary therapy chosen for patients with localized prostate cancer between the university hospital and its affiliated hospitals in Nara Uro-oncological research group registration 
BMC Urology  2011;11:6.
Background
We investigated the differences between the preferential primary therapy conceived by the primary doctors and the primary therapy actually conducted for prostate cancer patients in Nara, Japan.
Methods
The distribution of primary therapy and clinical characteristics of 2303 prostate cancer patients - diagnosed between 2004 and 2006 at Nara Medical University and its 23 affiliated hospitals - were assessed. Moreover, the preferential primary therapy for the patients at each clinical stage (cT1-T3bN0M0) conceived by the primary doctors was investigated and compared to the actual therapy.
Results
Of all patients, 51% received primary androgen deprivation therapy (PADT), 30% underwent radical prostatectomy (RP), and 14% received radiation therapy (RT). The preferential primary therapy for cT1-2N0M0 was RP (92%) while 38% of the patients actually received PADT (RP: 40%). For cT3aN0M0, the preferential primary therapy was both RP and external beam radiation therapy (EBRT) while 58% of the patients actually received PADT (RP: 16%, EBRT: 24%). For cT3bN0M0, the most preferential primary therapy was EBRT (46%) while 67% of the patients actually received PADT (EBRT: 21%). This trend was more notable in the affiliated hospitals than in the University hospital. The hospitals with lower volume of RP per year significantly conducted PADT compared with those with higher volume of RP.
Conclusions
PADT was commonly used to treat localized prostate cancer as well as locally advanced prostate cancer in Japan. There was a definite discrepancy between the preferential primary therapy conceived by the primary doctors and the actual therapy provided to the patients.
doi:10.1186/1471-2490-11-6
PMCID: PMC3095576  PMID: 21524283
22.  Immunocytochemical characterisation of cultures of human bladder mucosal cells 
BMC Urology  2011;11:5.
Background
The functional role of the bladder urothelium has been the focus of much recent research. The bladder mucosa contains two significant cell types: urothelial cells that line the bladder lumen and suburothelial interstitial cells or myofibroblasts. The aims of this study were to culture these cell populations from human bladder biopsies and to perform immunocytochemical characterisation.
Methods
Primary cell cultures were established from human bladder biopsies (n = 10). Individual populations of urothelial and myofibroblast-like cells were isolated using magnetic activated cell separation (MACS). Cells were slow growing, needing 3 to 5 weeks to attain confluence.
Results
Cytokeratin 20 positive cells (umbrella cells) were isolated at primary culture and also from patients' bladder washings but these did not proliferate. In primary culture, proliferating cells demonstrated positive immunocytochemical staining to cytokeratin markers (AE1/AE3 and A0575) as well fibroblasts (5B5) and smooth muscle (αSMA) markers. An unexpected finding was that populations of presumptive urothelial and myofibroblast-like cells, isolated using the MACS beads, stained for similar markers. In contrast, staining for cytokeratins and fibroblast or smooth muscle markers was not co-localised in full thickness bladder sections.
Conclusions
Our results suggest that, in culture, bladder mucosal cells may undergo differentiation into a myoepithelial cell phenotype indicating that urothelial cells have the capacity to respond to environmental changes. This may be important pathologically but also suggests that studies of the physiological function of these cells in culture may not give a reliable indicator of human physiology.
doi:10.1186/1471-2490-11-5
PMCID: PMC3104367  PMID: 21496348
urothelial cells; myofibroblasts; immunocytochemistry; human
23.  Hemangioma of the prostate - an unusual cause of lower urinary tract symptoms: Case report 
BMC Urology  2011;11:4.
Background
Hemangioma of the prostate gland is extremely rare and only a few cases have been reported. There have been several cases of hemangioma of posterior urethra, urinary bladder and periprostatic plexus in the literature, all presenting with hematuria or hematospermia. Diagnosis of prostatic hemangioma is difficult due to its rarity and unspecific symptoms such as hematuria, hematospermia or lower urinary tract symptoms. It cannot be detected by conventional examinations such as cystoscopy or standard rectal ultrasonography.
Case presentation
We present a case of prostatic hemangioma in an 84-year old male presenting with lower urinary tract symptoms. Bleeding has not been a feature in our case and diagnosis was not made until after operation. The patient was treated as a case of bladder neck outflow obstruction with transurethral resection of prostate gland and simultaneous bladder neck incisions. A period of self-catheterization was instituted due to postoperative urinary retention as the result of detrusor insufficiency.
Conclusion
Hemangioma of prostate gland is extremely rare and symptomatic prostatic hemangioma should be treated either by transurethral resection of prostate or laser evaporation.
doi:10.1186/1471-2490-11-4
PMCID: PMC3107823  PMID: 21486499
Hemangioma; Prostate; Transrectal ultrasound; Transurethral Resection of Prostate; Urinary bladder neck obstruction
24.  Sexual dysfunction among married couples living in Kumasi metropolis, Ghana 
BMC Urology  2011;11:3.
Background
Sexuality and its manifestation constitute some of the most complex of human behaviour and its disorders are encountered in community. Sexual dysfunction is more prevalent in women than in men. While studies examining sexual dysfunction among males and females in Ghana exist, there are no studies relating sexual problems in males and females as dyadic units. This study therefore investigated the prevalence and type of sexual disorders among married couples.
Method
The study participants consisted of married couples between the ages of 19 and 66 living in the province of Kumasi, Ghana. Socio-demographic information and Golombok-Rust Inventory of Sexual Satisfaction (GRISS) questionnaires were administered to 200 couples who consented to take part in the study. All 28 questions of the GRISS are answered on a five-point (Likert type) scale from "always", through "usually', "sometimes", and "hardly ever", to "never". Responses are summed up to give a total raw score ranging from 28-140. The total score and subscale scores are transformed using a standard nine point scale, with high scores indicating greater problems. Scores of five or more are considered to indicate SD. The study was conducted between July and September 2010.
Results
Out of a total of 200 married couples, 179 completed their questionnaires resulting in a response rate of 89.5%. The mean age of the participating couples as well as the mean duration of marriage was 34.8 ± 8.6 years and 7.8 ± 7.6 years respectively. The husbands (37.1 ± 8.6) were significantly older (p < 0.0001) than their corresponding wives (32.5 ± 7.9). After adjusting for age, 13-18 years of marriage life poses about 10 times significant risk of developing SD compared to 1-6 years of married life among the wives (OR: 10.8; CI: 1.1 - 49.1; p = 0.04). The total scores (6.0) as well as the percentage above the cut-off (59.2) obtained by the husbands compared to the total score (6.2) and the percentage above cut-off (61.5) obtained by the wives, indicates the likely presence of sexual dysfunction. The prevalence of impotence and premature ejaculation were 60.9% and 65.4% respectively from this study and the prevalence of vaginismus and anorgasmia were 69.3% and 74.9% respectively. The highest prevalence of SD subscales among the men was dissatisfaction with sexual act followed by infrequency, whereas the highest among the women was infrequency followed by anorgasmia. Dissatisfaction with sexual intercourse among men correlated positively with anorgasmia and wife's non-sensuality and infrequency of sex.
Conclusion
The prevalence of sexual dysfunction in married couples is comparable to prevalence rates in the general male and female population and is further worsened by duration of marriage. This could impact significantly on a couple's self-esteem and overall quality of life.
doi:10.1186/1471-2490-11-3
PMCID: PMC3058113  PMID: 21366917
25.  Discrepancy between radiological and pathological size of renal masses 
BMC Urology  2011;11:2.
Background
Tumor size is a critical variable in staging for renal cell carcinoma. Clinicians rely on radiological estimates of pathological tumor size to guide patient counseling regarding prognosis, choice of treatment strategy and entry into clinical trials. If there is a discrepancy between radiological and pathological measurements of renal tumor size, this could have implications for clinical practice. Our study aimed to compare the radiological size of solid renal tumors on computed tomography (CT) to the pathological size in an Australian population.
Methods
We identified 157 patients in the Westmead Renal Tumor Database, for whom data was available for both radiological tumor size on CT and pathological tumor size. The paired Student's t-test was used to compare the mean radiological tumor size and the mean pathological tumor size. Statistical significance was defined as P < 0.05. We also identified all cases in which post-operative down-staging or up-staging occurred due to discrepancy between radiological and pathological tumor sizes. Additionally, we examined the relationship between Fuhrman grade and radiological tumor size and pathological T stage.
Results
Overall, the mean radiological tumor size on CT was 58.3 mm and the mean pathological size was 55.2 mm. On average, CT overestimated pathological size by 3.1 mm (P = 0.012). CT overestimated pathological tumor size in 92 (58.6%) patients, underestimated in 44 (28.0%) patients and equaled pathological size in 21 (31.4%) patients. Among the 122 patients with pT1 or pT2 tumors, there was a discrepancy between clinical and pathological staging in 35 (29%) patients. Of these, 21 (17%) patients were down-staged post-operatively and 14 (11.5%) were up-staged. Fuhrman grade correlated positively with radiological tumor size (P = 0.039) and pathological tumor stage (P = 0.003).
Conclusions
There was a statistically significant but small difference (3.1 mm) between mean radiological and mean pathological tumor size, but this is of uncertain clinical significance. For some patients, the difference leads to a discrepancy between clinical and pathological staging, which may have implications for pre-operative patient counseling regarding prognosis and management.
doi:10.1186/1471-2490-11-2
PMCID: PMC3056852  PMID: 21342488

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