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1.  Renal papillary calcification and the development of calcium oxalate monohydrate papillary renal calculi: a case series study 
BMC Urology  2013;13:14.
Background
The objective of this study is to determine in a case series (four patients) how calcified deposits in renal papillae are associated with the development of calcium oxalate monohydrate (COM) papillary calculi.
Methods
From the recently collected papillary calculi, we evaluated retrospectively patients, subjected to retrograde ureteroscopy, with COM papillary lithiasis.
Results
The COM papillary calculi were found to result from subepithelial injury. Many of these lesions underwent calcification by hydroxyapatite (HAP), with calculus morphology and the amount of HAP in the concave zone dependent on the location of the calcified injury. Most of these HAP deposits grew, eroding the epithelium covering the renal papillae, coming into contact with urine and starting the development of COM calculi. Subepithelial HAP plaques may alter the epithelium covering the papillae, resulting in the deposit of COM crystals directly onto the epithelium. Tissue calcification depends on a pre-existing injury, the continuation of this process is due to modulators and/or crystallization inhibitors deficiency.
Conclusions
Since calculus morphology and the amount of detected HAP are dependent on the location and widespread of calcified injury, all types of papillary COM calculi can be found in the same patient. All patients had subepithelial calcifications, with fewer papillary calculi, demonstrating that some subepithelial calcifications did not further evolve and were reabsorbed. A high number of subepithelial calcifications increases the likelihood that some will be transformed into COM papillary calculi.
doi:10.1186/1471-2490-13-14
PMCID: PMC3599710  PMID: 23497010
Renal calculi; Pathologic calcification; Hydroxyapatite; Kidney papilla; Calcium oxalate monohydrate
2.  Safe digital isolation of the santorini plexus during radical retropubic prostatectomy 
BMC Urology  2013;13:13.
Background
We describe a safe and easily reproducible technique to control Santorini plexus during radical retropubic prostatectomy (RRP) which uses simple digital dissection.
Methods
We retrospectively reviewed 56 consecutive patients who underwent RRP for clinically localised prostate cancer from November 2008 to November 2010. Santorini plexus was isolated and secured in all patients using a new technique of simple digital dissection in which the index finger is used not to only localize the catheter inside the urethra, but also to develop the right plane between Santorini plexus and urethra. This is obtained by gentle bilateral digital dissection through the lateral aspects of periprostatic fascia which are eventually breached by the fingers, developing a right plane just above the urethra. Santorini plexus is then easily ligated and divided. Indicators of outcomes included estimated blood loss, transfusion requirements, operative time, positive margins and complication rates of the technique.
Results
The maneuver was successful in 53/56 (95%) patients. Mean (range) blood loss and overall operative time for RRP were 620 ml (100–1500) and 130 min. (80–190), respectively. Transfusion rate was 8,9% (5/56). Positive surgical margin rate was 14% (8/56). No complication related to the employed technique was recorded.
Conclusions
Digital dissection of Santorini plexus during RRP is simple and easily feasible. It speeds up the process of finding the right plane just above the urethra allowing good haemostasis in the surgical field and proper apical dissection.
doi:10.1186/1471-2490-13-13
PMCID: PMC3599675  PMID: 23445607
Digital isolation; Dorsal vein complex; Radical retropubic prostatectomy; Santorini plexus
3.  Identifying the quality of life effects of urinary incontinence with depression in an Australian population 
BMC Urology  2013;13:11.
Background
To explore the additive effect of urinary incontinence, in people with comorbid depression, on health related quality of life.
Methods
Males and females, 15 to 95 years (n = 3010, response rate 70.2%) were interviewed face to face in the 1998 Autumn South Australian Health Omnibus Survey.
Results
Self-reported urinary incontinence was found in 20.3% (n=610), and depression as defined by the PRIME-MD in 15.2% (n=459) of the survey population. Urinary incontinence with comorbid depression was found in 4.3% of the overall population. Univariate analysis showed that respondents with urinary incontinence and comorbid depression were more likely to be aged between 15 and 34 years and never married when compared to those with incontinence only. Multivariate analysis demonstrated that in people with incontinence, the risk of having comorbid depression was increased by an overall health status of Fair or Poor, or the perception that their incontinence was moderately or very serious. Respondents reporting that they experienced incontinence with comorbid depression scored significantly lower than those experiencing incontinence without depression on all dimensions of the SF-36.
The interaction of the presence of incontinence and the presence of depression was significantly associated with the dimensions of physical functioning.
Conclusions
Depression and incontinence both reduce QOL. When they occur together there appears to be an additive effect which affects both physical and mental health, perhaps by increasing a person’s negative perceptions of their illness. Clinicians should identify and manage comorbid depression when treating patients who have incontinence to improve their overall QOL.
doi:10.1186/1471-2490-13-11
PMCID: PMC3585815  PMID: 23413970
4.  Recent finding and new technologies in nephrolitiasis: a review of the recent literature 
BMC Urology  2013;13:10.
This review summarizes recent literature on advances regarding renal and ureteral calculi, with particular focus in areas of recent advances in the overall field of urolithiasis. Clinical management in everyday practice requires a complete understanding of the issues regarding metabolic evaluation and subgrouping of stone-forming patients, diagnostic procedures, effective treatment regime in acute stone colic, medical expulsive therapy, and active stone removal. In this review we focus on new perspectives in managing nephrolitihiasis and discuss recentadvances, including medical expulsive therapy, new technologies, and refinements of classical therapy such as shock wave lithotripsy, give a fundamental modification of nephrolithiasis management. Overall, this field appears to be the most promising, capable of new developments in ureterorenoscopy and percutaneous approaches. Further improvements are expected from robotic-assisted procedures, such as flexible robotics in ureterorenoscopy.
doi:10.1186/1471-2490-13-10
PMCID: PMC3599704  PMID: 23413950
Nephrolithiasis; New technologies; Diagnostic procedures; Risk factors; Ureterorenoscopy; Robotic-assisted surgery; Shock wave lithotripsy
5.  Retroperitoneal teratoma with somatic malignant transformation: A papillary renal cell carcinoma in a testicular germ cell tumour metastasis following platinum-based chemotherapy 
BMC Urology  2013;13:9.
Background
Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation.
Case presentation
A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed.
Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer.
Conclusions
To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens.
doi:10.1186/1471-2490-13-9
PMCID: PMC3577457  PMID: 23402579
Retroperitoneal teratoma; Malignant transformation; Germ cell tumour metastasis; Renal cell cancer
6.  The effect of indomethacin on the muscarinic induced contractions in the isolated normal guinea pig urinary bladder 
BMC Urology  2013;13:8.
Background
To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions.
Methods
The urethra and bladder of 9 male guinea pigs (weight 270–300 g) were removed and placed in an organ bath with Krebs’ solution. A catheter was passed through the urethra through which the intravesical pressure was measured. The muscarinic agonist arecaidine, the non-selective COX inhibitor indomethacin, and PGE2 were subsequently added to the organ bath. The initial average frequency and amplitude of spontaneous contractions in the first 2 minutes after arecaidine application were labelled Fini and Pini, respectively. The steady state frequency (Fsteady) and amplitude (Psteady) were defined as the average frequency and amplitude during the 5 minutes before the next wash out.
Results
Application of 1 μM PGE2 increased the amplitude of spontaneous contractions without affecting frequency. 10 μM of indomethacin reduced amplitude but not frequency.
The addition of indomethacin did not alter Fini after the first application (p = 0.7665). However, after the second wash, Fini was decreased (p = 0.0005). Fsteady, Psteady and Pini were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE2 addition..
Conclusions
Blocking PG synthesis decreased the cholinergically stimulated autonomous contractions in the isolated bladder. This suggests that PG could modify normal cholinergically evoked response. A combination of drugs inhibiting muscarinic receptors and PG function or production can then become an interesting focus of research on a treatment for overactive bladder syndrome.
doi:10.1186/1471-2490-13-8
PMCID: PMC3570383  PMID: 23388044
7.  Retroperitoneoscopic donor nephrectomy with a gel-sealed hand-assist access device 
BMC Urology  2013;13:7.
Background
The hand-assisted technique enables the rapid extraction of the graft, shortening the warm ischemia time (WIT), and the retroperitoneoscopic approach is potentially associated with a less incidence of postoperative ileus in donor nephrectomy for living kidney transplantation. The aim of this study was to assess the efficacy and safety of retroperitoneoscopic donor nephrectomy with a gel-sealed hand-assist access device (GelPort), which is a wound sealing device that permits the access of the hand to the surgical field, free trocar site choice within it, and rapid conversion to open surgery if necessary, while preserving the pneumoperitoneum/pneumoretroperitoneum.
Methods
Seventy-five consecutive donors receiving this procedure were retrospectively studied. A 2-cm skin incision was made at the midpoint between the tip of the 12th rib and superior border of the iliac bone in the midaxillary line, through which retroperitoneal space was made. Preperitoneal wound with a 6 – 7-cm pararectal incision in the upper abdominal region was connected to the retroperitoneal space. A GelPort was put inside the pararectal surgical wound. The principle was pure retroperitoneoscopic surgery; hand-assist was applied for retraction of the kidney in the renal vessel control and graft extraction.
Results
The mean operation time including waiting time for recipient preparation was 242.2±37.0 (range: 214.0–409.0) min, and the mean amount of blood loss was 164.3±146.6 (range: 10.0–1020.0) ml. The mean WIT was 2.8±1.0 (range: 1.0–6.0) min. The shortage of renal vessels or ureter was observed in none of the grafts. No donor experienced blood transfusion, open conversion, or injury of other organs. Blood loss was greater in patients with body mass index (BMI) of 25 kg/m2 or higher than in those with BMI of <25 kg/m2 (218.4±98.8 vs. 154.8±152.1 ml, P=0.031). No donor had postoperative ileus or reported wound pain leading to decreased activity of daily life or wound cosmetic problem.
Conclusions
Retroperitoneoscopic hand-assisted donor nephrectomy with the mentioned approach was suggested to be a feasible option without compromising safety, although further improvement in surgical techniques is warranted.
doi:10.1186/1471-2490-13-7
PMCID: PMC3598922  PMID: 23374442
Donor nephrectomy; Retroperitoneoscopy; Gel-sealed access device
8.  Improving prostate cancer detection in veterans through the development of a clinical decision rule for prostate biopsy 
BMC Urology  2013;13:6.
Background
We sought to improve prostate cancer (PC) detection through developing a prostate biopsy clinical decision rule (PBCDR), based on an elevated PSA and laboratory biomarkers. This decision rule could be used after initial PC screening, providing the patient and clinician information to consider prior to biopsy.
Methods
This case–control study evaluated men from the Tampa, Florida, James A. Haley (JH) Veteran’s Administration (VA) (N = 1,378), from January 1, 1998, through April 15, 2005. To assess the PBCDR we did all of the following: 1) Identified biomarkers that are related to PC and have the capability of improving the efficiency of PC screening; 2) Developed statistical models to determine which can best predict the probability of PC; 3) Compared each potential model to PSA alone using Receiver Operator Characteristic (ROC) curves, to evaluate for improved overall effectiveness in PC detection and reduction in (negative) biopsies; and 4) Evaluated dose–response relationships between specified lab biomarkers (surrogates for extra-prostatic disease development) and PC progression.
Results
The following biomarkers were related to PC: hemoglobin (HGB) (OR = 1.42 95% CI 1.27, 1.59); red blood cell (RBC) count (OR = 2.52 95% CI 1.67, 3.78); PSA (OR = 1.04 95% CI 1.03, 1.05); and, creatinine (OR = 1.55 95% CI 1.12, 2.15). Comparing all PC stages versus non-cancerous conditions, the ROC curve area under the curve (AUC) enlarged (increasing the probability of correctly classifying PC): PSA (alone) 0.59 (95% CI 0.55, 0.61); PBCDR model 0.68 (95% CI 0.65, 0.71), and the positive predictive value (PPV) increased: PSA 44.7%; PBCDR model 61.8%. Comparing PC (stages II, III, IV) vs. other, the ROC AUC increased: PSA (alone) 0.63 (95% CI 0.58, 0.66); PBCDR model 0.72 (95% CI 0.68, 0.75), and the PPV increased: 20.6% (PSA); PBCDR model 55.3%.
Conclusions
These results suggest evaluating certain common biomarkers in conjunction with PSA may improve PC prediction prior to biopsy. Moreover, these biomarkers may be more helpful in detecting clinically relevant PC. Follow-up studies should begin with replicating the study on different U.S. VA patients involving multiple practices.
doi:10.1186/1471-2490-13-6
PMCID: PMC3567946  PMID: 23356551
9.  MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1 
BMC Urology  2013;13:5.
Background
Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors.
Methods
After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression.
Results
Of the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038).
Conclusions
MDM2 SNP309 promoter polymorphism and mutations in p53 were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma. However, patients with abnormal p16 expression and a mutated p53 gene had a higher rate of and a shorter time to progression, and p53 gene mutation was associated with an abnormal immunohistochemistry for p53 at a cut-off of 50%.
doi:10.1186/1471-2490-13-5
PMCID: PMC3574032  PMID: 23356517
10.  Radiosensitization in prostate cancer: mechanisms and targets 
BMC Urology  2013;13:4.
Prostate cancer is the second most commonly diagnosed cancer in American men over the age of 45 years and is the third most common cause of cancer related deaths in American men. In 2012 it is estimated that 241,740 men will be diagnosed with prostate cancer and 28,170 men will succumb to prostate cancer. Currently, radiation therapy is one of the most common definitive treatment options for localized prostate cancer. However, significant number of patients undergoing radiation therapy will develop locally persistent/recurrent tumours. The varying response rates to radiation may be due to 1) tumor microenvironment, 2) tumor stage/grade, 3) modality used to deliver radiation, and 4) dose of radiation. Higher doses of radiation has not always proved to be effective and have been associated with increased morbidity. Compounds designed to enhance the killing effects of radiation, radiosensitizers, have been extensively investigated over the past decade. The development of radiosensitizing agents could improve survival, improve quality of life and reduce costs, thus benefiting both patients and healthcare systems. Herin, we shall review the role and mechanisms of various agents that can sensitize tumours, specifically prostate cancer.
doi:10.1186/1471-2490-13-4
PMCID: PMC3583813  PMID: 23351141
Cancer; Prostate; Radiation; Radiosensitizer
11.  Hereditary papillary renal cell carcinoma primarily diagnosed in a cervical lymph node: a case report of a 30-year-old woman with multiple metastases 
BMC Urology  2013;13:3.
Background
Papillary renal cell carcinoma is a rare cancer. Some cases can be attributed to individuals with hereditary renal cell carcinomas usually consisting of the clear cell subtype. In addition, two syndromes with hereditary papillary renal cell carcinoma have been described. One is the hereditary leiomyomatosis and renal cell carcinoma, which is characterized by cutaneous and uterine leiomyomas and renal cell carcinoma mostly consisting of the papillary renal cell carcinoma type II with a worse prognosis.
Case presentation
We describe a case of a 30-year-old woman with hereditary leiomyomatosis and renal cell carcinoma syndrome with extensively metastasized papillary renal cell carcinoma, primarily diagnosed in a cervical lymph node lacking leiomyomas at any site.
Conclusion
Papillary renal cell carcinoma in young patients should be further investigated for a hereditary variant like the hereditary leiomyomatosis and renal cell carcinoma even if leiomyomas could not be detected. A detailed histological examination and search for mutations is essential for the survival of patients and relatives.
doi:10.1186/1471-2490-13-3
PMCID: PMC3547807  PMID: 23320739
HLRCC; Fumarate hydratase (fh); Papillary renal cell cancer; Leiomyomatosis
12.  Focal cryosurgical ablation of the prostate: a single institute’s perspective 
BMC Urology  2013;13:2.
Background
With the stage migration of prostate cancer witnessed in the late 1990’s and early 2000’s along with the persistent morbidities associated with prostatectomy and radiation therapy, the concept of focal prostate cancer treatment remains quite attractive. Herein we evaluate the tolerability and non-oncologic outcomes of a highly select cohort of men that underwent focal cryoablation of the prostate for the treatment of localized prostate cancer.
Methods
Pre-operatively, erectile function was assessed by SHIM questionnaire while voiding symptoms were assessed by AUA symptom score. Twenty-six highly select patients (23 low-risk prostate cancer and 3 intermediate-risk prostate cancer) with documented minimal disease on saturation prostate biopsy underwent focal cryoablation of the prostate (24 hemi-ablation and 2 subtotal ablation). Subsequently, serum PSAs were obtained every 3 months for 2 years and then every 6 months thereafter. PSA failure was defined as an increase of 0.50 ng/ml over nadir. Mean follow-up was 19.1 months. Subjective assessment of erectile function and voiding was assessed post-operatively at each visit.
Results
Based on our PSA failure definition, 11.5% (3 patients) of the cohort experienced biochemical failure. In two of the three patients, localized disease was detected on subsequent transrectal ultrasound guided biopsy. These two patients went on to have favorable PSA nadirs after undergoing conventional definitive therapy (one patient had external beam radiation and one patient had whole gland cryoablation). Within the study cohort, 27% (7 patients) reported new post-operative erectile dysfunction requiring therapy while no patients reported new post-operative urinary incontinence or worsening of voiding symptoms.
Conclusion
These preliminary results add to the expanding body of literature that the minimally invasive focal cryosurgical ablation of the prostate is a safe procedure with few side effects. The true extent of cancer control remains in question, but in highly select patients, favorable PSA kinetics have been demonstrated. If confirmed by further studies with long-term follow-up, this treatment approach could have a profound effect on prostate cancer management.
doi:10.1186/1471-2490-13-2
PMCID: PMC3585847  PMID: 23311921
Prostate cancer; Therapy; Focal; Cryoablation
13.  Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model 
BMC Urology  2013;13:1.
Background
COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation.
Methods
LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1000 μM diclofenac. Next, a clonogenic assay was performed in which cells were subjected to irradiation (0 to 4 Gy) with or without diclofenac. COX-2 expression and other relevant molecules were measured by real-time PCR and immunohistochemistry after irradiation and diclofenac treatment. In addition, we assessed the tumor volumes of xenograft LNCaP-COX-2 cells treated with topical diclofenac with or without radiation therapy (RT).
Results
LNCaP-COX-2 and LNCaP-Neo cell lines experienced cytotoxic effects of diclofenac in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to RT than LNCaP-Neo cells. Furthermore, the addition of diclofenac sensitized LNCaP-COX-2 not but LNCaP-Neo cells to the cytocidal effects of radiation. In LNCaP-COX-2 cells, diclofenac enhanced radiation-induced apoptosis compared with RT alone. This phenomenon might be attributed to enhancement of RT-induced TRAIL expression as demonstrated by real-time PCR analysis. Lastly, tumor volumes of LNCaP-COX-2 cells xenograft treated with diclofenac or RT alone was >4-fold higher than in mice treated with combined diclofenac and radiation (p<0.05).
Conclusions
These in vitro and in vivo findings suggest that conventional COX inhibitor, diclofenac enhances the effect of RT on prostate cancer cells that express COX-2. Thus, diclofenac may have potential as radiosensitizer for treatment of prostate cancer.
doi:10.1186/1471-2490-13-1
PMCID: PMC3561196  PMID: 23289871
Prostate cancer; Radiation therapy; COX-2; TRAIL; Apoptosis; Topical therapy; Radiosensitizer; Diclofenac; Radioresistance
14.  Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer 
BMC Urology  2012;12:37.
Background
Bladder cancer is a significant cause of morbidity and mortality with a high recurrence rate. Early detection of bladder cancer is essential in order to remove the tumor, to preserve the organ and to avoid metastasis. The aim of this study was to analyze the differential expression of mitochondrial non-coding RNAs (sense and antisense) in cells isolated from voided urine of patients with bladder cancer as a noninvasive diagnostic assay.
Methods
The differential expression of the sense (SncmtRNA) and the antisense (ASncmtRNAs) transcripts in cells isolated from voided urine was determined by fluorescent in situ hybridization. The test uses a multiprobe mixture labeled with different fluorophores and takes about 1 hour to complete. We examined the expression of these transcripts in cells isolated from urine of 24 patients with bladder cancer and from 15 healthy donors.
Results
This study indicates that the SncmtRNA and the ASncmtRNAs are stable in cells present in urine. The test reveals that the expression pattern of the mitochondrial transcripts can discriminate between normal and tumor cells. The analysis of 24 urine samples from patients with bladder cancer revealed expression of the SncmtRNA and down-regulation of the ASncmtRNAs. Exfoliated cells recovered from the urine of healthy donors do not express these mitochondrial transcripts. This is the first report showing that the differential expression of these mitochondrial transcripts can detect tumor cells in the urine of patients with low and high grade bladder cancer.
Conclusion
This pilot study indicates that fluorescent in situ hybridization of cells from urine of patients with different grades of bladder cancer confirmed the tumor origin of these cells. Samples from the 24 patients with bladder cancer contain cells that express the SncmtRNA and down-regulate the ASncmtRNAs. In contrast, the hybridization of the few exfoliated cells recovered from healthy donors revealed no expression of these mitochondrial transcripts. This assay can be explored as a non-invasive diagnostic tool for bladder cancer.
doi:10.1186/1471-2490-12-37
PMCID: PMC3541257  PMID: 23249382
15.  Neoadjuvant hormonal therapy is a feasible option in laparoscopic radical prostatectomy 
BMC Urology  2012;12:36.
Background
Few reports can be found in the literature with respect to the impact of neoadjuvant hormonal therapy (NHT) on operative parameters on laparoscopic radical prostatectomy (LRP) in a large study. The aim of this study was to evaluate the safety and efficacy of NHT prior to LRP for locally confined prostate cancer.
Methods
From January 2004 to September 2009, 342 patients undergoing LRP were analyzed, specifically comparing 72 patients who received NHT to 270 who did not. All patients were in clinical stage T2 and nerve sparing LRP were not included.
Results
The mean patient age, preoperative prostate specific antigen (PSA), clinical stage, and biopsy Gleason grade were similar for the NHT and the non-NHT LRP groups. The median blood loss and the median operative time were also similar. There were no differences in the intraoperative complication rate of rectum injury, blood transfusion, and open surgery conversion. The positive surgical margin rate was significantly improved in NHT patients. Moreover, PSA recurrence within two years was significantly less in long-term NHT than in non-NHT patients.
Conclusions
LRP was shown as a safe and efficacious procedure in patients who have received NHT. Perioperative morbidity of NHT patients undergoing LRP appears equivalent to non-NHT patients, with lower positive surgical margin, and PSA recurrence rate.
doi:10.1186/1471-2490-12-36
PMCID: PMC3541356  PMID: 23249358
Prostate cancer; Neoadjuvant hormonal therapy; Laparoscopic radical prostatectomy
16.  Identification of prostaglandin receptors in human ureters 
BMC Urology  2012;12:35.
Background
Prostaglandins play an important role in ureteral obstruction, but the detailed expression profiles of the prostaglandin receptors (PTGER1, PTGER2, PTGER3, PTGER4, PTGFR) remain unknown in the different parts of the human ureter.
Methods
The expression pattern of PTGER1, PTGER2, PTGER3, PTGER4 and PTGFR was determined in human distal, mid and proximal ureter and renal pelvis samples using immunohistochemistry (protein levels) and quantitative real-time PCR (mRNA).
Results
PTGER1 was highly expressed in most samples irrespective of the ureteral localization; however, urothelial cells had higher levels of PTGER1 than smooth muscle cells. PTGFR was also moderately to strongly expressed in urothelial and smooth muscle cells. In comparison, PTGER2-4 expression was mostly unexpressed or weakly expressed in urothelial and smooth cells in all regions.
Conclusions
Our data indicate high levels of PTGER1 in ureters.
doi:10.1186/1471-2490-12-35
PMCID: PMC3576244  PMID: 23227994
Prostaglandin receptor; PTGER1; EP1; Ureter; Cyclooxygenase
17.  Unusual stent after ureteral substitution. A first case 
BMC Urology  2012;12:34.
Background
To the best of our knowledge this is the first case where a Silastic drain is used in ureteral surgery instead of a common urological stent. Patients coming from other institutions, especially in peripheral areas, can be treated with non conventional devices and if traditional imaging is inconclusive, computed tomography (CT) can provide valuable information to make the right diagnosis.
Case presentation
We present the unusual case of a 32F Silastic drain found inside the urinary tract in a female patient who had previously undergone ileal loop replacement of the left ureter for post-hysterectomy stricture at another Institution, and had subsequently repeated surgery due to persistent hydronephrosis. Radiological findings on plain abdominal X-ray were quite misleading, while CT allowed a correct assessment of the drain features.
Conclusion
While double J stents of different lengths, sizes and materials are used in ureteral surgery, the use of Silastic drains has not been previously reported. In light of the present experience we don’t suggest its routinely use.
doi:10.1186/1471-2490-12-34
PMCID: PMC3541236  PMID: 23191944
Ureteral stent; Ileal loop substitution; Abdominal X-ray; Multidetector computed tomography; Image processing
18.  Resistance profiles of urinary tract infections in general practice - an observational study 
BMC Urology  2012;12:33.
Background
Guideline recommendations on therapy in urinary tract infections are based on antibiotic resistance rates. Due to a lack of surveillance data, little is known about resistance rates in uncomplicated urinary tract infection (UTI) in general practice in Germany. In a prospective observational study, urine cultures of all women presenting with urinary tract infections in general practice were analysed. Resistance rates against antibiotics recommended in German guidelines on UTI are presented.
Methods
In a prospective, multi-center observational study general practitioner included all female patients ≥ 18 years with clinically suspected urinary tract infection. Only patients receiving an antibiotic therapy within the last two weeks were excluded.
Results
40 practices recruited 191 female patients (mean age 52 years; range 18–96) with urinary tract infections. Main causative agent was Escherichia coli (79%) followed by Enterococcus faecalis (14%) and Klebsiella pneumoniae (7.3%).
Susceptibiliy of E.coli as the main causative agent was highest against fosfomycin and nitrofurantoin, with low resistance rates of 4,5%; 2,2%. In 17,5%, E.coli was resistant to trimethoprim and in 8,5% to ciprofloxacin.
Conclusions
Resistance rates of uropathogens from unselected patients in general practice differ from routinely collected laboratory data. These results can have an impact on antibiotic prescribing and treatment recommendations.
doi:10.1186/1471-2490-12-33
PMCID: PMC3534546  PMID: 23171154
Urinary tract infection; Primary care; Drug resistance; Anti-bacterial agents
19.  Oral zinc supplementation restore high molecular weight seminal zinc binding protein to normal value in Iraqi infertile men 
BMC Urology  2012;12:32.
Background
Zinc in human seminal plasma is divided into three types of ligands which are high (HMW), intermediate (IMW), and low molecular weight ligands (LMW). The present study was aimed to study the effect of Zn supplementation on the quantitative and qualitative characteristics of semen along with Zinc Binding Protein levels in the seminal plasma in asthenozoospermic patients.
Methods
Semen samples were obtained from 37 fertile and 37 asthenozoospermic infertile men with matched age. The subfertile group was treated with zinc sulfate, every participant took two capsules per day for three months (each one 220mg). Semen samples were obtained (before and after zinc sulfate supplementation). After liquefaction seminal fluid at room temperature, routine semen analyses were performed. For determination of the amount of zinc binding proteins, the gel filtration of seminal plasma on Sephadex G-75 was performed. All the fractions were investigated for protein and for zinc concentration by atomic absorption spectrophotometry. Evaluation of chromatograms was made directly from the zinc concentration in each fraction.
Results
A significant high molecular weight zinc binding ligands percentage (HMW-Zn %) was observed in seminal plasma of fertile males compared with subfertile males. However, seminal low molecular weight ligands (LMW-Zn) have opposite behavior. The mean value of semen volume, progressive sperm motility percentage and total normal sperm count were increased after zinc sulfate supplementation.
Conclusions
Zinc supplementation restores HMW-Zn% in seminal plasma of asthenozoospermic subjects to normal value. Zinc supplementation elevates LMW-Zn% in seminal plasma of asthenozoospermic subjects to more than normal value.
Trial registration
ClinicalTrials.gov identifier NCT01612403
doi:10.1186/1471-2490-12-32
PMCID: PMC3503568  PMID: 23145537
Zinc; Zinc binding protein; Gel filtration; Asthenozoospermia; Semenogelin
20.  Urethral obstruction from dislodged bladder Diverticulum stones: a case report 
BMC Urology  2012;12:31.
Background
Secondary urethral stone although rare, commonly arises from the kidneys, bladder or are seen in patients with urethral stricture. These stones are either found in the posterior or anterior urethra and do result in acute urinary retention. We report urethral obstruction from dislodged bladder diverticulum stones. This to our knowledge is the first report from Nigeria and in English literature.
Case presentation
A 69 year old, male, Nigerian with clinical and radiological features of acute urinary retention, benign prostate enlargement and bladder diverticulum. He had a transurethral resection of the prostate (TURP) and was lost to follow up. He re-presented with retained urethral catheter of 4months duration. The catheter was removed but attempt at re-passing the catheter failed and a suprapubic cystostomy was performed. Clinical examination and plain radiograph of the penis confirmed anterior and posterior urethral stones. He had meatotomy and antegrade manual stone extraction with no urethra injury.
Conclusions
Urethral obstruction can result from inadequate treatment of patient with benign prostate enlargement and bladder diverticulum stones. Surgeons in resource limited environment should be conversant with transurethral resection of the prostate and cystolithotripsy or open prostatectomy and diverticulectomy.
doi:10.1186/1471-2490-12-31
PMCID: PMC3520759  PMID: 23134722
Urethral obstruction; Diverticulum stones; Urinary retention
21.  Construct validation of patient global impression of severity (PGI-S) and improvement (PGI-I) questionnaires in the treatment of men with lower urinary tract symptoms secondary to benign prostatic hyperplasia 
BMC Urology  2012;12:30.
Background
Lower urinary tract symptoms (LUTS) in aging men are often associated with benign prostatic hyperplasia (BPH). While regulatory evaluations of treatment benefit require an assessment of specific symptoms, a simpler approach to measuring patients’ perceptions of severity and symptom change may be particularly useful for clinical practice. The aim of this study was to provide evidence of the validity of the 1-item Patient Global Impression of Severity (PGI-S) and Improvement (PGI-I) questionnaires for use as outcome measures in the treatment of BPH-LUTS.
Methods
This was a secondary analysis of data from 4 randomized placebo-controlled 12-week trials evaluating tadalafil for the treatment of BPH-LUTS (N=1694). Visit 2 (V2 [beginning of a 4-week placebo lead-in period]) and endpoint assessments included International Prostate Symptom Score (IPSS), IPSS Quality of Life Index (IPSS-QoL), BPH Impact Index (BII), and peak urine flow (Qmax). PGI-S was only administered at V2 and PGI-I only at endpoint. Associations between the PGI-S or the PGI-I and the other assessments were analyzed by calculating Spearman rank correlation coefficients and performing analysis of variance (ANOVA).
Results
Spearman correlation coefficients were 0.43, 0.43, 0.53, and −0.09, between the PGI-S and IPSS, IPSS-QoL, BII, and Qmax baseline results (all P<0.001). Similar results were seen across race, ethnicity, and baseline severity (moderate LUTS versus severe LUTS). IPSS, IPSS-QoL, BII baseline scores (P <0.001) and Qmax values (P=0.003) were significantly different among the 4 PGI-S severity levels. Spearman correlation coefficients were 0.56, 0.53, 0.47 and −0.15 between the PGI-I and change in IPSS, IPSS-QoL, BII scores, and Qmax values from baseline to endpoint (all P<0.001). Similar results were seen across race, ethnicity, and baseline severity. Change in IPSS, IPSS-QoL, BII scores, and Qmax values (P<0.001) were significantly different among the PGI-I levels (i.e., patient perception of change in urinary symptoms).
Conclusions
This study demonstrated patients’ overall perceptions of their severity and change in BPH-LUTS can be captured in a way that is simple, valid, and easily administered in a research setting or clinical practice. Clinical parameters are weakly associated with patients’ perception of urinary symptoms, emphasizing the importance of a patient-reported assessment in the evaluation of BPH-LUTS treatment benefit.
doi:10.1186/1471-2490-12-30
PMCID: PMC3503561  PMID: 23134716
Patient global impression scale; Lower urinary tract symptoms; Construct validity
22.  Investigation of ejaculatory disorder by silodosin in the treatment of prostatic hyperplasia 
BMC Urology  2012;12:29.
Background
To assess the ejaculatory disorder caused by silodosin in the prostatic hyperplasia patients who carry out sexual actions (sexual intercourse, masturbation).
Method
The subjects of this study were 91 patients who had been clinically diagnosed to have LUTS/BPH at this hospital, who were administered silodosin at 4 mg twice a day, and who gave response to a questionnaire survey related to ejaculatory disorder. Sexual intercourse and masturbation were regarded as sexual actions in this study.
Results
Ejaculatory disorder occurred in 38 (42%) of the 91 silodosin administration cases. Forty (44%) of the 91 patients answered that they carried out sexual actions after oral intake of silodosin. When the investigation was conducted only in those who exercised sexual actions, ejaculatory disorder was observed in 38 (95%) of these 40 patients, indicating a high incidence. When asked if disturbed by the ejaculatory disorder, 29 (76%) of the 38 patients who had ejaculatory disorder answered yes. Oral silodosin was discontinued due to the ejaculatory disorder in 2 (5%) of these patients. On the whole, the discontinuation rate of oral silodosin was 2% (2/91 patients).
Conclusion
It was demonstrated that the administration of silodosin induced ejaculatory disorder at a high incidence. Since it is possible that the high frequency of ejaculatory disorder by silodosin may reduce QOL, it is considered necessary to provide sufficient information related to ejaculatory disorder at the time of treatment with silodosin.
doi:10.1186/1471-2490-12-29
PMCID: PMC3507909  PMID: 23082785
Silodosin; α1 blocker; Ejaculatory disorder; Adverse reaction; Sexual action
23.  Minimal percentage of dose received by 90% of the urethra (%UD90) is the most significant predictor of PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer 
BMC Urology  2012;12:28.
Background
To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer.
Methods
We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone.
Results
Fifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce.
Conclusions
Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.
doi:10.1186/1471-2490-12-28
PMCID: PMC3487947  PMID: 22974428
Prostate cancer; Brachytherapy; PSA bounce; Post-dosimetry; UD90 (%)
24.  Genetic variation in SPAG16 regions encoding the WD40 repeats is not associated with reduced sperm motility and axonemal defects in a population of infertile males 
BMC Urology  2012;12:27.
Background
SPAG16 is a critical structural component of motile cilia and flagella. In the eukaryotic unicellular algae Chlamydomonas, loss of gene function causes flagellar paralysis and prevents assembly of the “9 + 2” axoneme central pair. In mice, we have previously shown that loss of Spag16 gene function causes male infertility and severe sperm motility defects. We have also reported that a heterozygous mutation of the human SPAG16 gene reduces stability of the sperm axonemal central apparatus.
Methods
In the present study, we analyzed DNA samples from 60 infertile male volunteers of Western European (Italian) origin, to search for novel SPAG16 gene mutations, and to determine whether increased prevalence of SPAG16 single nucleotide polymorphisms (SNPs) was associated with infertility phenotypes. Semen parameters were evaluated by light microscopy and sperm morphology was comprehensively analyzed by transmission electron microscopy (TEM).
Results
For gene analysis, sequences were generated covering exons encoding the conserved WD40 repeat region of the SPAG16 protein and the flanking splice junctions. No novel mutations were found, and the four SNPs in the assessed gene region were present at expected frequencies. The minor alleles were not associated with any assessed sperm parameter in the sample population.
Conclusions
Analysis of the SPAG16 regions encoding the conserved WD repeats revealed no evidence for association of mutations or genetic variation with sperm motility and ultrastructural sperm characteristics in a cohort of Italian infertile males.
doi:10.1186/1471-2490-12-27
PMCID: PMC3487941  PMID: 22963137
Sperm ultrastructure; Axoneme; Motile cilia; Male infertility; Central apparatus; Semen analysis
25.  Content validity and test-retest reliability of patient perception of intensity of urgency scale (PPIUS) for overactive bladder 
BMC Urology  2012;12:26.
Background
The Patient Perception of Intensity of Urgency Scale (PPIUS) is a patient-reported outcome instrument intended to measure the intensity of urgency associated with each urinary or incontinence episode. The objectives of this study were to assess the content validity, test-retest reliability, and acclimation effect of the PPIUS in overactive bladder (OAB) patients.
Methods
Patients undergoing treatment for OAB were recruited to participate in a non-interventional study by completing a three-day micturition diary including the PPIUS for three consecutive weeks. Following completion of the three-week study, participants from two select sites also completed a cognitive interview to assess their comprehension of the PPIUS.
Results
Thirty-nine participants successfully completed the three-week test-retest study; twelve of these participants completed the cognitive interview. Test-retest reliability was high based on intra-class correlation coefficient of 0.95. Among stable patients, the difference between the mean ratings of any two weeks was non-significant. Among the twelve interview participants, nine found it simple to choose a PPIUS rating for each of their micturition episodes and most found the urgency rating definitions consistent with their urgency experiences.
Conclusions
The results demonstrated content validity based on qualitative interviews, and excellent test-retest reliability among stable patients. In addition, no acclimation effect was observed among stable patients. These findings support the use of the PPIUS as a reliable measure of urgency in both clinical trial and real life settings. The validity of PPIUS could be further established with future studies investigating the relationship between discretely graded urgency and incontinence continuum.
doi:10.1186/1471-2490-12-26
PMCID: PMC3479079  PMID: 22958621
Over active bladder; OAB; Urinary urgency; Urge incontinence; Patient perception of intensity of urgency scale; PPIUS

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