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1.  microRNA-99a acts as a tumor suppressor and is down-regulated in bladder cancer 
BMC Urology  2014;14:50.
Background
Increasing evidences have documented that microRNAs (miRNAs) act as oncogenes or tumor suppressors in a variety types of cancer. The discovery of tumor associated miRNAs in serum of patients gives rise to extensive investigation of circulating miRNAs in many human cancers which support the use of plasma/serum miRNAs as noninvasive means of cancer detection. However, the aberrant expression of miRNAs and the circulating miRNAs in bladder cancer are less reported.
Methods
We used Taqman probe stem-loop real-time PCR to accurately measure the levels of miR-99a in bladder cancer cell lines, 100 pairs of bladder cancer tissues, the adjacent non-neoplastic tissues and plasma collected from bladder cancer patients or control patients. miR-99a mimics were re-introduced into bladder cancer cells to investigate its role on regulating cell proliferation which was measured by CCK-8 assay and cell cycle analysis.
Results
miR-99a was significantly down-regulated in bladder cancer tissues, and even the lower expression of miR-99a was correlative with the more aggressive phenotypes of bladder cancer. Meanwhile, enforced expression of miR-99a can inhibit the cell proliferation of bladder cancer cells. Furthermore, investigation of the expression of miR-99a in plasma of bladder cancer patients showed that miR-99a was also decreased in plasma of bladder cancer patients. The results strongly supported miR-99a as the potential diagnostic marker of bladder cancer.
Conclusions
Our data indicated that miR-99a might act as a tumor suppressor in bladder cancer and was significantly down-regulated in development of bladder cancer.
doi:10.1186/1471-2490-14-50
PMCID: PMC4083872  PMID: 24957100
Bladder cancer; miR-99a; Circulation miRNA
2.  Disease-specific outcomes of Radical Prostatectomies in Northern Norway; a case for the impact of perineural infiltration and postoperative PSA-doubling time 
BMC Urology  2014;14:49.
Background
Prostate cancer is the most common male malignancy and a mayor cause of mortality in the western world. The impact of clinicopathological variables on disease related outcomes have mainly been reported from a few large US series, most of them not reporting on perineural infiltration. We therefore wanted to investigate relevant cancer outcomes in patients undergoing radical prostatectomy in two Norwegian health regions with an emphasis on the impact of perineural infiltration (PNI) and prostate specific antigen- doubling time (PSA-DT).
Methods
We conducted a retrospective analysis of 535 prostatectomy patients at three hospitals between 1995 and 2005 estimating biochemical failure- (BFFS), clinical failure- (CFFS) and prostate cancer death-free survival (PCDFS) with the Kaplan-Meier method. We investigated clinicopathological factors influencing risk of events using cox proportional hazard regression.
Results
After a median follow-up of 89 months, 170 patients (32%) experienced biochemical failure (BF), 36 (7%) experienced clinical failure and 15 (3%) had died of prostate cancer. pT-Stage (p = 0.001), preoperative PSA (p = 0.047), Gleason Score (p = 0.032), non-apical positive surgical margins (PSM) (p = 0.003) and apical PSM (p = 0.031) were all independently associated to BFFS. Gleason score (p = 0.019), PNI (p = 0.012) and non-apical PSM (p = 0.002) were all independently associated to CFFS while only PNI (P = 0.047) and subgroups of Gleason score were independently associated to PCDFS. After BF, patients with a shorter PSA-DT had independent and significant worse event-free survivals than patients with PSA-DT > 15 months (PSA-DT = 3-9 months, CFFS HR = 6.44, p < 0.001, PCDFS HR = 13.7, p = 0.020; PSA-DT < 3 months, CFFS HR = 11.2, p < 0.001, PCDFS HR = 27.5, p = 0.006).
Conclusions
After prostatectomy, CFFS and PCDFS are variable, but both are strongly associated to Gleason score and PNI. In patients with BF, PSA-DT was most strongly associated to CF and PCD. Our study adds weight to the importance of PSA-DT and re-launches PNI as a strong prognosticator for clinically relevant endpoints.
doi:10.1186/1471-2490-14-49
PMCID: PMC4067377  PMID: 24929427
3.  Prostate cancer outcomes in France: treatments, adverse effects and two-year mortality 
BMC Urology  2014;14:48.
Background
This very large population-based study investigated outcomes after a diagnosis of prostate cancer (PCa) in terms of mortality rates, treatments and adverse effects.
Methods
Among the 11 million men aged 40 years and over covered by the general national health insurance scheme, those with newly managed PCa in 2009 were followed for two years based on data from the national health insurance information system (SNIIRAM). Patients were identified using hospitalisation diagnoses and specific refunds related to PCa and PCa treatments. Adverse effects of PCa treatments were identified by using hospital diagnoses, specific procedures and drug refunds.
Results
The age-standardised two-year all-cause mortality rate among the 43,460 men included in the study was 8.4%, twice that of all men aged 40 years and over. Among the 36,734 two-year survivors, 38% had undergone prostatectomy, 36% had been treated by hormone therapy, 29% by radiotherapy, 3% by brachytherapy and 20% were not treated. The frequency of treatment-related adverse effects varied according to age and type of treatment. Among men between 50 and 69 years of age treated by prostatectomy alone, 61% were treated for erectile dysfunction and 24% were treated for urinary disorders. The frequency of treatment for these disorders decreased during the second year compared to the first year (erectile dysfunction: 41% vs 53%, urinary disorders: 9% vs 20%). The frequencies of these treatments among men treated by external beam radiotherapy alone were 7% and 14%, respectively. Among men between 50 and 69 years with treated PCa, 46% received treatments for erectile dysfunction and 22% for urinary disorders. For controls without PCa but treated surgically for benign prostatic hyperplasia, these frequencies were 1.5% and 6.0%, respectively.
Conclusions
We report high survival rates two years after a diagnosis of PCa, but a high frequency of PCa treatment-related adverse effects. These frequencies remain underestimated, as they are based on treatments for erectile dysfunction and urinary disorders and do not reflect all functional outcomes. These results should help urologists and general practitioners to inform their patients about outcomes at the time of screening and diagnosis, and especially about potential treatment-related adverse effects.
doi:10.1186/1471-2490-14-48
PMCID: PMC4067687  PMID: 24927850
Prostate cancer; Treatments; Adverse effects; Prostatectomy; Radiotherapy; Complications; Population-based study
4.  Prediction of open urinary tract in laparoscopic partial nephrectomy by virtual resection plane visualization 
BMC Urology  2014;14:47.
Background
The purpose of this study is presenting a method to predict the presence of an open urinary tract and the position of the opening in laparoscopic partial nephrectomy from three dimensional (3D) computed tomography (CT) images by using novel image segmentation and visualization techniques.
Methods
From CT images of patients who underwent laparoscopic partial nephrectomy, 3D regions of the kidney, urinary tract, and tumor were segmented. For each patient, multiple virtual resection planes of the kidney with different surgical margins (1 mm to 5 mm, every 1 mm) were generated and the presence of an open urinary tract and the position of the opening were predicted from the images.
Results
We compared the predictions with actual operations in 5 cases by using recorded video of the operations and operative notes. In terms of the presence of an open urinary tract, agreement of the predictions and the intraoperative results was obtained in all patients. The expected positions of the openings were close to those in the actual operations.
Conclusions
We have developed a method to virtually visualize the resection plane of laparoscopic partial nephrectomy. Image segmentation methods used in this study were precise and effective. The comparison indicated that our method accurately predicted the presence of an open urinary tract and the position of the opening and provided useful preoperative information.
doi:10.1186/1471-2490-14-47
PMCID: PMC4074416  PMID: 24927795
Laparoscopic surgery; Partial nephrectomy; Simulator; Urinary tract opening
5.  Use of buccal mucosa grafts for urethral reconstruction in children: a retrospective cohort study 
BMC Urology  2014;14:46.
Background
The use of buccal mucosa grafts (BMG) for urethral reconstruction has increased in popularity over the last several decades. Our aim was to describe our institutional experience with and outcomes after BMG urethroplasty.
Methods
We conducted a retrospective cohort study of boys undergoing BMG urethral reconstruction. Preoperative and perioperative characteristics and postoperative outcomes were evaluated.
Results
Twenty-nine patients (median age 8.2 years) underwent BMG urethroplasty from 1995–2012. Of the 10 patients undergoing 1-stage repairs, 6 had tubularized grafts, the last of which was performed in 2000 due to an unacceptably high revision rate (100%). A 2-stage approach was elected for 19 patients (median follow-up 21.3 months). Complications including stricture, fistula, or chordee were seen in 60% of patients completing both stages and 32% required ≥1 revision. However, 71% of 2-stage patients were free of significant problems at last follow-up.
Conclusions
We found BMG to be a reasonable option for use in complex pediatric urethral reconstruction. Tubularized grafts had poor results, and we no longer use them. We favor a 2-stage approach for all patients except those with “simple” non-hypospadiac strictures. Although revision procedures were not uncommon, the majority of patients were ultimately free of long-term problems.
doi:10.1186/1471-2490-14-46
PMCID: PMC4066324  PMID: 24902693
Stricture; Hypospadias; Urethroplasty; Buccal mucosa; Oral mucosa
6.  Procalcitonin and C-reactive protein in urinary tract infection diagnosis 
BMC Urology  2014;14:45.
Background
Urinary infections are a common type of pediatric disease, and their treatment and prognosis are closely correlated with infection location. Common clinical manifestations and laboratory tests are insufficient to differentiate between acute pyelonephritis and lower urinary tract infection. This study was conducted to explore a diagnostic method for upper and lower urinary tract infection differentiation.
Methods
The diagnostic values of procalcitonin (PCT) and C-reactive protein (CRP) were analyzed using the receiver operating characteristic curve method for upper and lower urinary tract infection differentiation. PCT was determined using chemiluminescent immunoassay.
Results
The PCT and CRP values in children with acute pyelonephritis were significantly higher than those in children with lower urinary tract infection (3.90 ± 3.51 ng/ml and 68.17 ± 39.42 mg/l vs. 0.48 ± 0.39 ng/ml and 21.39 ± 14.92 mg/l). The PCT values were correlated with the degree of renal involvement, whereas the CRP values failed to show such a significant correlation. PCT had a sensitivity of 90.47% and a specificity of 88% in predicting nephropathia, whereas CRP had sensitivity of 85.71% and a specificity of 48%.
Conclusions
Both PCT and CRP can be used for upper and lower urinary tract infection differentiation, but PCT has higher sensitivity and specificity in predicting pyelonephritis than CRP. PCT showed better results than CRP. PCT values were also correlated with the degree of renal involvement.
doi:10.1186/1471-2490-14-45
PMCID: PMC4074860  PMID: 24886302
Urinary tract infections; Acute pyelonephritis; Receiver operating characteristic curve; Procalcitonin
7.  Prostate volume and biopsy tumor length are significant predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy 
BMC Urology  2014;14:43.
Background
Gleason pattern 3 less often has molecular abnormalities and often behaves indolent. It is controversial whether low grade small foci of prostate cancer (PCa) on biopsy could avoid immediate treatment or not, because substantial cases harbor unfavorable pathologic results on prostatectomy specimens. This study was designed to identify clinical predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy.
Methods
Retrospective review of 1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013. Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage ≤ cT2a, Gleason score (GS) ≤ 6, up to two positive biopsies, and no more than 50% of cancer involvement in any core. The associations between preoperative data and unfavorable pathologic results of prostatectomy specimens, and oncological outcome were analyzed. The definition of insignificant cancer consisted of pathologic stage ≤ pT2, GS ≤ 6, and an index tumor volume < 0.5 mL (classical) or 1.3 mL (redefined).
Results
Pathologic stage ≥ pT3, upgraded GS, index tumor volume ≥ 0.5 mL, and ≥ 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83 (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year recurrence-free survival was 86.8%, and the insignificant cancers essentially did not relapse regardless of the surgical margin status. MRI-estimated prostate volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and findings of magnetic resonance imaging were associated with the presence of classical and redefined insignificant cancer. Large prostate volume and short tumor length on biopsy remained as independent predictors in multivariate analysis.
Conclusions
Favorable features of biopsy often are followed by adverse pathologic findings on prostatectomy specimens despite fulfilling the established criteria. The finding that prostate volume is important does not simply mirror many other studies showing PSAD is important, and the clinical criteria for risk assessment before definitive therapy or active surveillance should incorporate these significant factors other than clinical T-staging or PSAD to minimize under-estimation of cancer in Japanese patients with low-risk PCa.
doi:10.1186/1471-2490-14-43
PMCID: PMC4047262  PMID: 24886065
Predictive factor; Insignificant cancer; Index tumor volume; Prostate volume; Biopsy tumor length
8.  Influence of sildenafil on blood oxygen saturation of the obstructed bladder 
BMC Urology  2014;14:44.
Background
Blood oxygen saturation (BOS) is decreased in a low-compliant, overactive obstructed bladder. The objective of this study is to determine the effect of Sildenafil (SC) on bladder function and BOS) in an in vivo animal model of bladder outlet obstruction.
Methods
Thirty-two guinea pigs; sham operated (n = 8), sham operated + SC (n = 8), urethrally obstructed (n = 8) and urethrally obstructed + SC (n = 8) were studied during an 8 week period. BOS of the bladder wall was measured by differential path-length spectroscopy (DPS) before obstruction, at day 0, and at week 8. The bladder function was evaluated by urodynamic studies every week.
Results
Before surgery and after sham operation all study parameters were comparable. After sham operation, bladder function and BOS did not change. In the obstructed group the urodynamic parameters were deteriorated and BOS was decreased. In the group obstruction + SC, bladder compliance remained normal and overactivity occurred only sporadic. BOS remained unchanged compared to the sham group and was significantly higher compared to the obstruction group.
Conclusions
In an obstructed bladder the loss of bladder function is accompanied by a significant decrease in BOS. Treatment of obstructed bladders with SC yields a situation of high saturation, high bladder compliance and almost no overactivity. Maintaining the microcirculation of the bladder wall might result in better bladder performance without significant loss of bladder function. Measurement of BOS and interventions focussing on tissue microcirculation may have a place in the evaluation / treatment of various bladder dysfunctions.
doi:10.1186/1471-2490-14-44
PMCID: PMC4060762  PMID: 24886184
Bladder dysfunction; Bladder outlet obstruction; Guinea pig; Hypoxia; PDE5 inhibitor
9.  Wide-neck renal artery aneurysm: parenchymal sparing endovascular treatment with a new device 
BMC Urology  2014;14:42.
Background
Renal artery aneurysm is a rare disorder with a high mortality rate in the event of rupture, the most frequent complication, which can also occur in lesions smaller than those indicated for treatment by current criteria. Surgery is still the first-line treatment, although a growing trend toward endovascular management of visceral artery aneurysms has emerged because of the high efficacy and low invasiveness that has been demonstrated by several authors. Treatment of wide-necked aneurysms and, depending on location, those at renal artery bifurcations or distal branches is more complex and may require invasive surgical techniques, such as bench surgery.
Case presentation
We describe the successful use of a new neurointerventional coil to treat an enlarging wide-necked segmental-branch renal aneurysm in an elderly woman who was not a candidate for surgery because of several comorbidities.
Conclusions
The technique described allowed safe, successful treatment of a wide-necked aneurysm in an unfavorable vascular territory, reducing the risk of downstream artery embolization and consequent parenchymal damage and decreased renal function. In similar cases, other endovascular devices have often proven to be ineffective at nephron sparing. To validate the safety and efficacy of this system, more cases treated in this manner should be studied.
doi:10.1186/1471-2490-14-42
PMCID: PMC4070645  PMID: 24885940
Renal artery aneurysm; Visceral artery aneurysm; Wide-neck aneurysm; Embolization; Penumbra; Microcoil embolization
10.  Prognostic factors for recurrence-free and overall survival after adrenalectomy for metastatic carcinoma: a retrospective cohort pilot study 
BMC Urology  2014;14:41.
Background
The survival benefits of adrenalectomy (ADx) in the setting of metastatic cancer and prognostic factors for recurrence-free (RFS) and overall survival (OS) after adrenalectomy for metastatic carcinoma are still under debate. We evaluated the impact of clinicopathological variables on RFS and OS after ADx for metastatic carcinoma in patients with primary cancer.
Methods
A total of 32 patients undergoing ADx for metastatic cancer between 2004 and 2012 at two tertiary medical centers. Metastases were regarded as synchronous (<6 months) or metachronous (≥6 months) depending on the interval after primary surgery. Associations of perioperative clinicopathologic variables with RFS and OS were analyzed using Cox regression models.
Results
In total, 32 patients received ADx for metastatic primary tumors located in the lung (n = 11), colon (n = 4), liver (n = 5), stomach (n = 3), kidney (n = 4), pancreas (n = 2), glottis, esophagus, cervix, and ovary (n = 1 each). The overall recurrence rate after adrenalectomy was 62.5% (n = 20). By univariate analysis, C-reactive protein, inflammation-based prognosis score, and adrenalectomy for curative intent were associated with RFS and OS. Independent prognostic factors for shorter RFS were operative method (laparoscopy HR 4.68, 95% CI 1.61-13.61, p = 0.005) and inflammation-based prognostic score (HR 11.8, 95% CI 2.50-55.7, p = 0.002). For shorter OS, synchronous metastasis (HR 3.05, 95% CI 1.07-11.94, p = 0.048) and inflammation-based prognostic score (HR 6.65, 95% CI 1.25-35.23, p = 0.026) were identified as independent prognostic factors.
Conclusions
Our pilot study suggests that synchronous disease and inflammation-based prognostic score are significant prognostic factors for survival and should be considered when performing ADx for metastatic diseases.
doi:10.1186/1471-2490-14-41
PMCID: PMC4035762  PMID: 24885814
Adrenalectomy; Neoplasm metastasis; Prognosis; Survival
11.  Inferior vena cava prosthetic replacement in a patient with horseshoe kidney and metastatic testicular tumor: technical considerations and review of the literature 
BMC Urology  2014;14:40.
Background
Seminomatous and non-seminomatous Germ Cell Tumors (GCT) of the testis are a rare cancer, with an estimated incidence of 56.3 per million white males and 10 per million black males in the United States.
The association between non-seminomatous GCT and horseshoe kidney is a rare event and is seen in about 1.3% of patients requiring retroperitoneal lymph node dissection. To our knowledge, no cases have been reported in which replacement of the IVC was also necessary.
Case presentation
We report the case of a 22-year-old man with horseshoe kidney and metastatic non-seminomatous germ cell tumor involving the wall of the inferior vena cava.
Following post-chemotherapy retroperitonal lymph node dissection, the inferior vena cava was replaced with an expanded polytetrafluoroethylene graft.
At 2-years follow-up, the patient was in good health and the graft was patent. No clinical or diagnostic signs of renal impairment or recurrence of neoplastic disease were noted.
Conclusion
Radical surgery is warranted in patients with non-seminomatous germ cell tumor metastasizing to the retroperitoneal lymph nodes. When vena cava replacement is required, and the situation is further complicated by horseshoe kidney, as in this case, surgical technique will rely on multidisciplinary surgical treatment planning by a team composed of urologists, vascular surgeons and oncologists.
doi:10.1186/1471-2490-14-40
PMCID: PMC4039323  PMID: 24885698
Testis; Neoplasm GCT; PTFE
12.  New grading system for upper urinary tract dilation using magnetic resonance urography in patients with Neurogenic Bladder 
BMC Urology  2014;14:38.
Background
In patients with neurogenic bladder (NB), elevated intravesical pressures can be transmitted to the upper urinary tract, causing hydronephrosis (HN) and ureteral dilation (UD), which are referred to as upper urinary tract dilation (UUTD). Ureteral obstruction at the bladder wall is another cause for UUTD, but is less of a concern. UUTD can lead to chronic renal failure. Therefore, evaluation and protection of UUT function is extremely important in the management for NB. Currently, the most common method by which to detect HN and UD is ultrasonography (US). The Society for Fetal Urology (SFU) established an US HN grading system in 1993, but this system was found to have some defects. The purpose of this study is to describe a new grading system for UUTD, including both HN and UD, based on magnetic resonance urography (MRU) and to correlate the new grading system with the SFU grading system for HN.
Methods
A retrospective review of 70 patients with unilateral or bilateral UUTD was completed. Ninety-five sides in patients with UUTD were graded by the MRU-UUTD and SFU-HN grading systems. The results from the two grading systems were compared for each UUTD.
Results
The MRU-UUTD grading system revealed the following percentages for each grade: grade 0, 0; 1, 10.5%; 2, 19%; 3, 42.1%; and 4, 28.4%. The SFU-HN grading system revealed the following percentages for each grade: 0, 0; 1, 10.5%; 2, 19%; 3, 36.8%; and 4, 33.7%. There was no significant systematic difference between the two grading systems (p > 0.05), but a significant difference between grades 3 and 4 (p < 0.05).
Conclusions
The MRU-UUTD grading system correlates well with SFU-HN grade, provides an objective and comprehensive evaluation for UUTD, and can be used for longitudinal monitoring of UUTD. This new grading system allows for better informed clinical decision-making, identifying changes in UUTD.
doi:10.1186/1471-2490-14-38
PMCID: PMC4046082  PMID: 24885460
Upper urinary tract dilation; Grade; Hydronephrosis; Ureteral dilation; Magnetic resonance urography; Neurogenic bladder
13.  Primary mucin-producing urothelial-type adenocarcinoma of the prostatic urethra diagnosed on TURP: a case report and review of literature 
BMC Urology  2014;14:39.
Background
Mucin-producing urothelial-type adenocarcinoma of the prostatic urethra is extremely rare. These lesions must be differentiated from other mucinous tumors including mucin-producing prostatic adenocarcinoma and metastases from either colonic or bladder primaries.
Case presentation
We report here a case of urothelial-type adenocarcinoma arising from the prostatic urethra. The patient is an 81 year-old man with a history of pT1 urothelial cell carcinoma of the bladder status post trans-urethral resection of bladder tumor (TURBT) who initially presented with irritative lower urinary tract symptoms and mucosuria refractory to Flomax and finasteride. A shared decision was made for the patient to undergo trans-urethral resection of prostate (TURP). At the time of surgery, a papillary tumor emanating from the prostatic urethra was found and no urothelial lesions were noted in the bladder. Pathology of the resected prostatic chips revealed an invasive adenocarcinoma with intestinal-type differentiation that stained positive for CK7, CK20, and villin, but negative for PSA, PSAP, uroplakin, and CDX-2. Colonoscopy was normal and CT scan did not show any evidence of colonic lesions nor visceral or lymph node metastases. Thus, the patient was diagnosed with a primary urothelial-type adenocarcinoma of the prostatic urethra.
Conclusion
Herein we review the literature regarding this unusual entity, and discuss the differential diagnosis, immunohistochemistry, and the importance of correctly identifying this rare tumor.
doi:10.1186/1471-2490-14-39
PMCID: PMC4059493  PMID: 24885582
Mucin-producing adenocarcinoma; Prostatic urethra; Trans-urethral resection of prostate; Urothelial-type adenocarcinoma; Adenocarcinoma
14.  Development of an in vitro model to measure bioactivity of botulinum neurotoxin A in rat bladder muscle strips 
BMC Urology  2014;14:37.
Background
Botulinum toxin A (BoNT-A) is a new treatment modality in various causes of bladder dysfunction; like neurogenic detrusor overactivity and overactive bladder. The best technique of administrating BoNT-A in patients is unknown. A validated in vitro model could be used to investigate newer intravesical administration techniques of BoNT-A. In this study, we describe the development and validation of in vitro model to measure inhibitory effects of BoNT-A on bladder strip contractions.
Methods
Rat bladder strips were mounted in organ baths filled with Krebs’ solution. The strips were stimulated chemically (80 mM potassium chloride, 1 μM carbachol) and electrically (Electrical Field Stimulation (EFS) 100 shocks, 50 V, 20 Hz, every 3 minutes). The viability of the strips was measured by carbachol stimulation at the beginning and at the end of the experiments. The strips were incubated in various concentrations of BoNT-A (0.03, 0.2, 0.3 nM). Controls were incubated in Krebs’ solution only. The inhibition of strip contraction induced by EFS was measured. These measurements were statistically analyzed with a log-logistic model representing diffusion.
Results
All strips remained viable during the experiments. Inhibition of strip contraction was observed after incubation with 0.3 nM BoNT-A. The measurements fitted to a log-logistic model describing diffusion of BoNT-A in the bladder strip. The parameters of the log-logistic model representing diffusion were significant for 0.3 nM BoNT-A. Incubation with 0.2 nM BoNT-A showed insignificant results for 2 out of 3 runs. Incubation with 0.03 nM BoNT-A did not result in significant inhibition of strip contractions.
Conclusions
An in vitro model was developed and validated in which the inhibitory effect of low concentrations of BoNT-A on bladder strip contractions can be measured.
doi:10.1186/1471-2490-14-37
PMCID: PMC4064817  PMID: 24885301
Bladder; Botulinum toxin; Type A; In vitro
15.  Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts 
BMC Urology  2014;14:36.
Background
Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guérin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts.
Methods
Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards’ modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS).
Results
Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression.
Conclusions
The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.
doi:10.1186/1471-2490-14-36
PMCID: PMC4049499  PMID: 24885195
Ezrin; Urothelial bladder cancer; Prognosis
16.  One-stage dorsal inlay oral mucosa graft urethroplasty for anterior urethral stricture 
BMC Urology  2014;14:35.
Background
Anterior urethral stricture remains a great challenge. We reported our clinical technique and results by using inlay dorsal buccal mucosal graft urethroplasty for repair of anterior urethral stricture.
Methods
From January 2005 to July 2008, 87 male patients (range from 9 to 72 years old) with anterior urethral stricture have been treated by one-stage dorsal inlay oral mucosal graft (OMG) urethroplasty. All patients gave written informed consent for their participation. All patients showed that urethral plate had been either scarred or removed previously. In our surgery, the urethra was dissected dorsally and scar of the urethral plate was removed. The remnant urethral plate was split at midline and a buccal mucosa patch was inserted between the two parts. Neourethra was tubularized and covered with dartos flap. The pre-operative assessments included clinical data, urine analysis, uroflowmetry, retrograde and voiding cystogram, urethral ultrasonography and endoscopy. Postoperatively, the flow rate and void residual volume were analyzed by uroflowmetry and sonography. Any further instrumentation to assist voiding was considered as failure.
Results
After 12 to 48 months (mean: 25.8 months), 78 patients (89.66%) have shown good results by the one-stage urethroplasty. However, 9 patients (10.3%) required further treatment due to recurrence, while 6 patients (6.9%) had fistula.
Conclusions
This one-stage dorsal inlay approach using dorsal oral mucosal grafts is a reliable method to create a substitute urethral plate for tubularization. This approach represents a safe option for anterior urethral stricture patients especially with grossly scarred urethral plate.
doi:10.1186/1471-2490-14-35
PMCID: PMC4030733  PMID: 24885070
17.  Is there a role for anterior zone sampling as part of saturation trans-rectal ultrasound guided prostate biopsy? 
BMC Urology  2014;14:34.
Background
The prostatic anterior zone (AZ) is not targeted routinely by TRUS guided prostate biopsy (TRUS-Pbx). MRI is an accurate diagnostic tool for AZ tumors, but is often unavailable due to cost or system restrictions. We examined the diagnostic yield of office based AZ TRUS-Pbx.
Methods
127 men at risk for AZ tumors were studied: Patients with elevated PSA and previous extended negative TRUS-Pbx (group 1, n = 78) and actively surveyed low risk prostate cancer patients (group 2, n = 49). None of the participants had a previous AZ biopsy. Biopsy template included suspicious ultrasonic areas, 16 peripheral zone (PZ), 4 transitional zone (TZ) and 6 AZ cores. All biopsies were performed by a single urologist under local peri-prostatic anaesthetic, using the B-K Medical US System, an end-firing probe 4-12 MHZ and 18 ga/25 cm needle. All samples were reviewed by a single specialized uro-pathologist. Multivariate analysis was used to detect predictors for AZ tumors accounting for age, PSA, PSA density, prostate volume, BMI, and number of previous biopsies.
Results
Median PSA was 10.4 (group 1) and 7.3 (group 2). Age (63.9, 64.5), number of previous biopsies (1.5) and cores (17.8, 21.3) and prostate volume (56.4 cc, 51 cc) were similar for both groups. The overall diagnostic yield was 34.6% (group 1) and 85.7% (group 2). AZ cancers were detected in 21.8% (group 1) and 34.7% (group 2) but were rarely the only zone involved (1.3% and 4.1% respectively). Gleason ≥ 7 AZ cancers were often accompanied by equal grade PZ tumors. In multivariate analysis only prostate volume predicted for AZ tumors. Patients detected with AZ tumors had significantly smaller prostates (36.9 cc vs. 61.1 cc p < 0.001). Suspicious AZ ultrasonic findings were uncommon (6.3%).
Conclusions
TRUS-Pbx AZ sampling rarely improves the diagnostic yield of extended PZ sampling in patients with elevated PSA and previous negative biopsies. In low risk prostate cancer patients who are followed by active surveillance, AZ sampling changes risk stratification in 6% but larger studies are needed to define the role of AZ sampling in this population and its correlation with prostatectomy final pathological specimens.
doi:10.1186/1471-2490-14-34
PMCID: PMC4018265  PMID: 24884966
Anterior zone; Prostate biopsy; Prostate cancer; Saturation biopsy; Trans-rectal ultrasound
18.  Nadir PSA level and time to nadir PSA are prognostic factors in patients with metastatic prostate cancer 
BMC Urology  2014;14:33.
Background
Primary androgen deprivation therapy (PADT) is the most effective systemic therapy for patients with metastatic prostate cancer. Nevertheless, once PSA progression develops, the prognosis is serious and mortal. We sought to identify factors that predicted the prognosis in a series of patients with metastatic prostate cancer.
Methods
Two-hundred eighty-six metastatic prostate cancer patients who received PADT from 1998 to 2005 in Nara Uro-Oncology Research Group were enrolled. The log-rank test and Cox’s proportional hazards model were used to determine the predictive factors for prognosis; rate of castration-resistant prostate cancer (CRPC) and overall survival.
Results
The median age, follow-up period and PSA level at diagnosis were 73 years, 47 months and 174 ng/mL, respectively. The 5-year overall survival rate was 63.0%. The multivariable analysis showed that Gleason score (Hazard ratio [HR]:1.362; 95% confidence interval [C.I.], 1.023-1.813), nadir PSA (HR:6.332; 95% C.I., 4.006-9.861) and time from PADT to nadir (HR:4.408; 95% C.I., 3.099-6.271) were independent prognostic factors of the incidence of CRPC. The independent parameters in the multivariate analysis that predicted overall survival were nadir PSA (HR:5.221; 95% C.I., 2.757-9.889) and time from PADT to nadir (HR:4.008; 95% C.I., 2.137-7.517).
Conclusions
Nadir PSA and time from PADT to nadir were factors that affect both CRPC and overall survival in a cohort of patients with metastatic prostate cancer. Lower nadir PSA level and longer time from PADT to nadir were good for survival and progression.
doi:10.1186/1471-2490-14-33
PMCID: PMC4018264  PMID: 24773608
Prostate cancer; Metastasis; Risk factors
19.  Scrotal extratesticular schwannoma: a case report and review of the literature 
BMC Urology  2014;14:32.
Background
Schwannomas are tumours arising from Schwann cells, which sheath the peripheral nerves. Here, we report a rare case of left intrascrotal, extratesticular schwannoma. Although rare, scrotal localisation of schwannomas has been reported in male children, adult men, and elderly men. They are usually asymptomatic and are characterised by slow growth. Patients generally present with an intrascrotal mass that is not associated with pain or other clinical signs, and such cases are self-reported by most patients. Imaging modalities (such as ultrasonography, computed tomography, and magnetic resonance imaging) can be used to determine tumour size, exact localisation, and extension. However, the imaging findings of schwannoma are non-specific. Therefore, only complete surgical excision can result in diagnosis, based on histological and immunohistochemical analyses. If the tumour is not entirely removed, recurrences may develop, and, although malignant change is rare, this may occur, especially in patients with a long history of an untreated lesion. Thus, follow up examinations with clinical and imaging studies are recommended for scrotal schwannomas.
Case presentation
A 52-year-old man presented with a 3-year history of asymptomatic scrotal swelling. Physical examination revealed a palpable, painless, soft mass in the left hemiscrotum. After surgical removal of the mass, its histological features indicated schwannoma.
Conclusions
Schwannoma should be considered in cases of masses that are intrascrotal but extratesticular. Ultrasonography provides the best method of confirming the paratesticular localisation of the tumour, before surgical removal allows histopathological investigation and definitive diagnosis. Surgery is the standard therapeutic approach. To prevent recurrence, particular care should be taken to ensure complete excision. This case report includes a review of the literature on scrotal schwannomas.
doi:10.1186/1471-2490-14-32
PMCID: PMC4030735  PMID: 24776090
Scrotal schwannoma; Diagnosis; Histopathology
20.  External validation of risk classification in patients with docetaxel-treated castration-resistant prostate cancer 
BMC Urology  2014;14:31.
Background
Castration-resistant prostate cancer (CRPC) patients have poor prognoses, and docetaxel (DTX) is among the few treatment options. An accurate risk classification to identify CRPC patient groups for which DTX would be effective is urgently warranted. The Armstrong risk classification (ARC), which classifies CRPC patients into 3 groups, is superior; however, its usefulness remains unclear, and further external validation is required before clinical use. This study aimed to examine the clinical significance of the ARC through external validation in DTX-treated Japanese CRPC patients.
Methods
CRPC patients who received 2 or more DTX cycles were selected for this study. Patients were classified into good-, intermediate-, and poor-risk groups according to the ARC. Prostate-specific antigen (PSA) responses and overall survival (OS) were calculated and compared between the risk groups. A multivariate analysis was performed to clarify the relationship between the ARC and major patient characteristics.
Results
Seventy-eight CRPC patients met the inclusion criteria. Median PSA levels at DTX initiation was 20 ng/mL. Good-, intermediate-, and poor-risk groups comprised 51 (65%), 17 (22%), and 10 (13%) patients, respectively. PSA response rates ≥30% and ≥50% were 33%, 41%, and 30%, and 18%, 41%, and 20% in the good-, intermediate-, and poor-risk groups, respectivcixely, with no significant differences (p = 0.133 and 0.797, respectively). The median OS in the good-, intermediate-, and poor-risk groups were statistically significant (p < 0.001) at 30.1, 14.2, and 5.7 months, respectively. A multivariate analysis revealed that the ARC and PSA doubling time were independent prognostic factors.
Conclusions
Most of CRPC patients were classified into good-risk group according to the ARC and the ARC could predict prognosis in DTX-treated CRPC patients.
Trial registration
University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number, UMIN000011969.
doi:10.1186/1471-2490-14-31
PMCID: PMC3997751  PMID: 24742323
Castration-resistant prostate cancer; Docetaxel; Risk classification; Validation study
21.  Concern for overtreatment using the AUA/ASTRO guideline on adjuvant radiotherapy after radical prostatectomy 
BMC Urology  2014;14:30.
Background
Recently, three prospective randomized trials have shown that adjuvant radiotherapy (ART) after radical prostatectomy for the patients with pT3 and/or positive margins improves biochemical progression-free survival and local recurrence free survival. But, the optimal management of these patients after radical prostatectomy is an issue which has been debated continuously. The object of this study was to determine the necessity of adjuvant radiotherapy (ART) by reviewing the outcomes of observation without ART after radical prostatectomy (RP) in patients with pathologic indications for ART according to the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline.
Methods
From a prospectively maintained database, 163 patients were eligible for inclusion in this study. These men had a pathological stage pT2–3 N0 with undetectable PSA level after RP and met one or more of the three following risk factors: capsular perforation, positive surgical margins, or seminal vesicle invasion. We excluded the patients who had received neoadjuvant hormonal therapy or adjuvant treatment, or had less than 24 months of follow-up. To determine the factors that influenced biochemical recurrence-free (BCR), univariate and multivariate Cox proportional hazards analyses were performed.
Results
Among the 163 patients, median follow-up was 50.5 months (24.0-88.2 months). Of those men under observation, 27 patients had BCR and received salvage radiotherapy (SRT). The multivariate Cox analysis showed that BCR was marginally associated with pre-operative serum PSA (P = 0.082), and the pathologic GS (HR, 4.063; P = 0.001) was an independent predictor of BCR. More importantly, in 87 patients with pre-operative PSA < 6.35 ng/ml and GS ≤ 7, only 3 developed BCR.
Conclusions
Of the 163 patients who qualified for ART based on the current AUA/ASTRO guideline, only 27 (16.6%) developed BCR and received SRT. Therefore, using ART following RP using the current recommendation may be an overtreatment in an overwhelming majority of the patients.
doi:10.1186/1471-2490-14-30
PMCID: PMC4005471  PMID: 24708639
Radical prostatectomy; Radiotherapy; Biochemical recurrence
22.  Approach via a small retroperitoneal anterior subcostal incision in the supine position for gasless laparoendoscopic single-port radical nephrectomy: initial experience of 42 patients 
BMC Urology  2014;14:29.
Background
Gasless laparoendoscopic single-port surgery (GasLESS) for radical nephrectomy (GasLESSRN) in the flank position is a minimally invasive treatment option for patients with T1–3 renal cell carcinoma (RCC). However, RCC patients considered suitable for supine positioning rather than flank positioning for radical nephrectomy are occasionally encountered. This study evaluated the safety and feasibility of approach via a small retroperitoneal anterior subcostal incision (RASI) in the supine position for GasLESSRN (RASI-GasLESSRN) on the basis of our initial experience.
Methods
RASI-GasLESSRN was performed on 42 patients with RCC or suspected RCC from 2011–2013. The RASI, which was 6 cm long in principle, was made parallel to the tip of the rib from the lateral border of rectus abdominis muscle toward the flank in the supine position. The specimen was extracted via the RASI using a retrieval device. All procedures were performed retroperitoneally under flexible endoscopy with reusable instruments and without carbon dioxide insufflation or insertion of hands into the operative field.
Results
RASI-GasLESSRN was successfully performed in all patients without complications. The mean incision length was 6.3 cm, mean operative time was 198 minutes, and mean blood loss was 284 mL. All 42 patients were classified as Clavien grade I. The mean times to oral feeding and walking were 1.1 and 2 days, respectively. The mean number of postoperative days required for patients to be dischargeable was 3.7 days.
Conclusions
The approach via a small RASI in the supine position for GasLESSRN is a safe and feasible technique. RASI-GasLESSRN in the supine position is an alternative minimally invasive treatment option, especially for RCC patients considered suitable for supine positioning.
doi:10.1186/1471-2490-14-29
PMCID: PMC3977956  PMID: 24708621
Retroperitoneal anterior subcostal incision; Supine position; Renal cell carcinoma; Radical nephrectomy; Laparoendoscopic single-port surgery; Gasless laparoendoscopic single-port surgery
23.  A combined index to classify prognostic comorbidity in candidates for radical prostatectomy 
BMC Urology  2014;14:28.
Background
In patients with early prostate cancer, stratification by comorbidity could be of importance in clinical decision making as well as in characterizing patients enrolled into clinical trials. In this study, we investigated several comorbidity classifications as predictors of overall mortality after radical prostatectomy, searching for measures providing complementary prognostic information which could be combined into a single score.
Methods
The study sample consisted of 2205 consecutive patients selected for radical prostatectomy with a mean age of 64 years and a mean follow-up of 9.2 years (median: 8.6). Seventy-four patients with incomplete tumor-related data were excluded. In addition to age and tumor-related parameters, six comorbidity classifications and the body mass index were assessed as possible predictors of overall mortality. Kaplan-Meier curves and Mantel-Haenszel hazard ratios were used for univariate analysis. The impact of different causes of death was analyzed by competing risk analysis. Cox proportional hazard models were calculated to analyze combined effects of variables.
Results
Age, Gleason score, tumor stage, Charlson score, American Society of Anesthesiologists (ASA) physical status class and body mass index were identified a significant predictors of overall mortality in the multivariate analysis regardless whether two-sided and three-sided stratifications were used. Competing risk analysis revealed that the excess mortality in patients with a body mass index of 30 kg/m2 or higher was attributable to competing mortality including second cancers, but not to prostate cancer mortality.
Conclusion
Stratifying patients by a combined consideration of the comorbidity measures Charlson score, ASA classification and body mass index may assist clinical decision making in elderly candidates for radical prostatectomy.
doi:10.1186/1471-2490-14-28
PMCID: PMC3986600  PMID: 24678762
Prostate cancer; Radical prostatectomy; Comorbidity; Overall survival; Competing mortality; ASA classification; Charlson score; Body mass index; Cox proportional hazard models
24.  The effect of smoking on spontaneous passage of distal ureteral stones 
BMC Urology  2014;14:27.
Background
Animal studies have shown that nicotine affects the peristalsis of the ureter. The aim of the study is to analyze the effect of smoking on spontaneous passage of distal ureteral stones.
Methods
88 patients in whom distal ureteral stone below 10 mm diameter diagnosed with helical computerized tomography enhanced images were reviewed. Patients were grouped as either smokers (n:33) or non smokers (n:50). Follow-up for spontaneous passage of stones was limited with 4 weeks. Patients did not receive any additional medical treatment other than non-steroid anti inflamatory drugs only during painful renal colic episodes.
Two groups were compared with the chi-square test in terms of passing the stone or not. Stone passage was confirmed with either the patient collecting the stone during urination or by helical CT.
Results
Smoking habits was present in 30(34%) patients and the frequency in both groups were similar (smokers: 23(76%) vs non-smokers: 46(79%)). Spontaneous passage of the stone was observed in 69(78%) patients. The two groups were comparable in terms of patien age, male to female ratio and stone size. Stone passage decreased as stone diameter increased. Total stone passage rates were similar in both groups (smokers: 76% vs. non-smokers: 79%) (p > 0.05). Passage of stones > 4 mm was observed in 46% and 67% of smokers and non-smokers respectively. However passage of stones with a diameter ≤ 4 mm were similar in both groups (smokers: 100% vs non-smokers: 92%) (p > 0.05).
Conclusion
Smoking has neither a favorable nor un-favorable effect on spontaneous passage of distal ureteral stones. However, spontaneous passage rates in patients with a stone diameter > 4 mm was lower in smokers. These results should be further confirmed with studies including larger numbers of patients.
doi:10.1186/1471-2490-14-27
PMCID: PMC3994427  PMID: 24655408
Ureteral stone; Smoking habits; Nicotine; Distal stones; Spontaneous passage
25.  Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma 
BMC Urology  2014;14:26.
Background
Tyrosine kinase inhibitors (TKIs) have been used as standard therapy for patients with advanced renal cell carcinoma (RCC). However, information on factors predicting response to treatment with TKIs is lacking. This study aimed to assess the association between initial tumor size, involved organs, pre-treatment C-reactive protein (CRP) levels, and reduction in tumor size in patients with clear cell RCC (CCRCC) treated with sunitinib.
Methods
Patients with advanced CCRCC with target lesions with a maximum diameter ≥ 10 mm treated with sunitinib were evaluated. The tumor diameter representing the best overall response was designated as the post-treatment tumor diameter.
Results
A total of 179 lesions in 38 patients were analyzed. Organ-specific analysis demonstrated that pre-treatment diameter of lung metastatic lesions had a moderate inverse association with percent reduction in post-treatment tumor diameter (R = 0.341). Lung lesions showed significantly greater percent reductions in diameter than liver and kidney lesions (P = 0.007 and 0.002, respectively). Furthermore, based on a CRP cut-off level of 2.0 mg/dl, mean tumor size reduction was significantly greater in patients with low CRP levels than in patients with high CRP levels in lesions with diameters < 20 mm (P = 0.002). CRP level had no effect on mean size reduction in lesions with a diameter ≥ 20 mm.
Conclusions
Patients with CCRCC with smaller lung metastatic lesions and lower CRP levels may achieve greater percent reductions in tumor size with sunitinib therapy than patients with extra-pulmonary lesions, large lung lesions, and/or higher CRP levels.
doi:10.1186/1471-2490-14-26
PMCID: PMC3975282  PMID: 24612599
Advanced renal cell carcinoma; Sunitinib; Tumor size; Tumor response; C-reactive protein

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