BioMed Research International: Urology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. A New Double Stranded RNA Suppresses Bladder Cancer Development by Upregulating p21Waf1/CIP1 Expression Mon, 30 Mar 2015 12:59:07 +0000 We have previously demonstrated that miR-1180-5p has potent ability to upregulate p21 expression by targeting promoter and inhibit bladder cancer. This prompted us to conjecture that a candidate dsRNA (dsP21-397) with perfect complementarity to the miR-1180-5p target site of p21 promoter may also trigger p21 expression. Transfection of dsP21-397 into T24 and EJ cells significantly activated p21 expression at 72 h and the activation presented in a time-course and dose-dependent manner. Moreover, the p21-activated activities of dsP21-397 and miR-1180-5p are not significantly different. Overexpression of p21 downregulated Cyclin D1, CDK4/6, and Cyclin A2 expression, and thereby induced cell cycle arrest and inhibited proliferation. Moreover, dsP21-397 suppressed bladder cancer largely depended on manipulating p21. In conclusion, our study identifies a pair of miRNA-dsRNA mediating endogenous p21 overexpression. Chenghe Wang, Qiangqiang Ge, Zhong Chen, Jia Hu, Fan Li, Xiaodong Song, Hua Xu, and Zhangqun Ye Copyright © 2015 Chenghe Wang et al. All rights reserved. Haematuria in Postrenal Transplant Patients Mon, 30 Mar 2015 06:22:46 +0000 Haematuria has a prevalence of 12% in the postrenal transplant patient population. It heralds potentially dangerous causes which could threaten graft loss. It is important to consider causes in light of the unique, urological, and immunological standpoints of these patients. We review the literature on common causes of haematuria in postrenal transplant patients and suggest the salient approach to the evaluation of this condition. A major cause of haematuria is urinary tract infections. There should be a higher index of suspicion for mycobacterial, fungal, and viral infection in this group of immunosuppressed patients. Measures recommended in the prevention of urinary tract infections include early removal of foreign bodies as well as prophylactic antibiotics during the early transplant phase. Another common cause of haematuria is that of malignancies, in particular, renal cell carcinomas. When surgically managing cancer in the setting of a renal transplant, one has to be mindful of the limited retropubic space and the need to protect the anastomoses. Other causes include graft rejections, recurrences of primary disease, and calculus formation. It is important to perform a comprehensive evaluation with the aid of an experienced multidisciplinary transplant team. Ziting Wang, Anantharaman Vathsala, and Ho Yee Tiong Copyright © 2015 Ziting Wang et al. All rights reserved. Application of Long-Acting VLHL PAI-1 during Sutureless Partial Nephrectomy in Mice Reduces Bleeding Thu, 26 Mar 2015 11:59:23 +0000 PAI-1 prevents lysis of blood clot by inhibiting the urokinase and tPA induced conversion of plasminogen to plasmin. VLHL PAI-1 protein mutant was created to extend half-life over 700 hours. The objective of this paper was to test VLHL PAI-1 effects on bleeding during partial nephrectomy in mice. All animals had a left partial nephrectomy after intravenous infusion of saline or tPA. The animals were divided into four groups. Group 1 was infused with saline and kidney was exposed to saline too; Group 2 was infused with saline and kidney was exposed to PAI-1. Group 3 was infused with tPA and kidney was exposed to saline, while Group 4 was infused with tPA and kidney was exposed to PAI-1. Preweighed gauze containing PAI-1 or saline was then applied to the kidney for 30 minutes. The gauze was afterward weighed and blood loss was measured by subtracting the preweight of gauze from the final weight. We have observed a statistically significant () reduction of bleeding in PAI-1-treated group in comparison to saline and tPA-treated groups. Based on these results we propose that VLHL PAI-1 can be used therapeutically in limiting the flow of blood from renal wounds. Khaled Shahrour, Rick Keck, and Jerzy Jankun Copyright © 2015 Khaled Shahrour et al. All rights reserved. Ureteral Involvement and Diabetes Increase the Risk of Subsequent Bladder Recurrence after Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma Sun, 22 Mar 2015 11:38:18 +0000 Objectives. To investigate the prognostic factors for bladder recurrence after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UUT-UC). Methods. From 1994 to 2012, 695 patients with UUT-UC treated with RNU were enrolled in National Taiwan University Medical Center. Among them, 532 patients with no prior bladder UC history were recruited for analysis. We assessed the impact of potentially prognostic factors on bladder recurrence after RNU. Results. The median follow-up period was 47.8 months. In the Cox model, ureteral involvement and diabetes mellitus (DM) were significantly associated with a higher bladder recurrence rate in the multivariate analysis (hazard ratio [HR]: 1.838; and HR: 1.821; , resp.). In the Kaplan-Meier analysis, DM patients with concomitant ureteral UC experienced about a threefold increased risk of bladder recurrence as compared to those without both factors (HR: 3.222; ). Patients with either of the two risk factors experienced about a twofold increased risk as compared to those without both factors (with DM, HR: 2.184, ; with ureteral involvement, HR: 2.006, ). Conclusions. Ureteral involvement and DM are significantly related to bladder recurrence after RNU in patients with UUT-UC. Che-Yuan Hu, Yu-Chieh Tsai, Shuo-Meng Wang, Chao-Yuan Huang, Huai-Ching Tai, Chung-Hsin Chen, Yeong-Shiau Pu, Wei-Chou Lin, and Kuo-How Huang Copyright © 2015 Che-Yuan Hu et al. All rights reserved. Retrograde Intrarenal Surgery versus Percutaneous Lithotripsy to Treat Renal Stones 2-3 cm in Diameter Tue, 03 Mar 2015 12:21:43 +0000 Objective. Retrograde intrarenal surgery (RIRS) performed using a flexible ureterorenoscope marked the beginning of a new era in urology. Today, even staghorn stones are successfully treated via RIRS. The recommended treatment for larger stones is percutaneous nephrolithotomy (PNL). However, the question of whether PNL or RIRS should be the first-line treatment option for larger stones remains controversial. In this study, we contribute to the debate by comparing the success and complication rates of PNL and RIRS that were used to treat renal pelvis stones 2-3 cm in diameter. Materials and Methods. The medical records of 154 patients (74 PNL, 80 RIRS) were retrospectively evaluated. PNL patients were placed in Group 1 and RIRS patients in Group 2. Results. The complete stone-free rates were 95.5% in the PNL group and 80.6% in the RIRS group 1 month postoperatively (). The respective complication rates (evaluated using the Clavien system) were 13.5% and 8.8% (). Conclusions. RIRS affords a comparable success rate, causes fewer complications than PNL, and seems to be a promising alternative to PNL when larger stones are to be treated. Prospective randomized controlled trials are needed to confirm these findings. Kursad Zengin, Serhat Tanik, Nihat Karakoyunlu, Nevzat Can Sener, Sebahattin Albayrak, Can Tuygun, Hasan Bakirtas, M. Abdurrahim Imamoglu, and Mesut Gurdal Copyright © 2015 Kursad Zengin et al. All rights reserved. Is Visual Registration Equivalent to Semiautomated Registration in Prostate Biopsy? Mon, 02 Mar 2015 10:23:56 +0000 In magnetic resonance iimaging- (MRI-) ultrasound (US) guided biopsy, suspicious lesions are identified on MRI, registered on US, and targeted during biopsy. The registration can be performed either by a human operator (visual registration) or by fusion software. Previous studies showed that software registration is fairly accurate in locating suspicious lesions and helps to improve the cancer detection rate. Here, the performance of visual registration was examined for ability to locate suspicious lesions defined on MRI. This study consists of 45 patients. Two operators with differing levels of experience (1 and 18 years) performed visual registration. The overall spatial difference by the two operators in 72 measurements was 10.6 ± 6.0 mm. Each operator showed a spatial difference of 9.4 ± 5.1 mm (experienced; 39 lesions) and 12.1 ± 6.6 mm (inexperienced; 33 lesions), respectively. In a head-to-head comparison of the same 16 lesions from 12 patients, the spatial differences were 9.7 mm ± 4.9 mm (experienced) and 13.4 mm ± 7.4 mm (inexperienced). There were significant differences between the two operators (unpaired, P value = 0.042; paired, P value = 0.044). The substantial differences by the two operators suggest that visual registration could improperly and inaccurately target many tumors, thereby potentially leading to missed diagnosis or false characterization on pathology. Jin Tae Kwak, Cheng William Hong, Peter A. Pinto, Molly Williams, Sheng Xu, Jochen Kruecker, Pingkun Yan, Baris Turkbey, Peter L. Choyke, and Bradford J. Wood Copyright © 2015 Jin Tae Kwak et al. All rights reserved. Genitourethral Reconstruction Mon, 23 Feb 2015 09:55:12 +0000 Ralf Herwig, Salvatore Sansalone, and Peter Rehder Copyright © 2015 Ralf Herwig et al. All rights reserved. The Role of Androgen Receptor Expression in the Curative Treatment of Prostate Cancer with Radiotherapy: A Pilot Study Sun, 22 Feb 2015 11:46:54 +0000 The androgen receptor (AR) and its signaling pathway play an important role in the development and progression of prostate cancer (PCa). In the setting of primary treatment of PCa with radiotherapy (RT), where the AR can be expected to be of more importance, studies evaluating the AR expression are lacking. The goal of this research is to evaluate AR protein expression in hormone-naive PCa patients treated by RT and investigate its possible prognostic role. Primary biopsy samples of 18 patients treated with primary RT were analyzed including the corresponding clinical information. AR protein expression of the tumor epithelium (with highest Gleason pattern) and the surrounding stroma was quantified using the Quick score for steroid receptors. The differential expression between epithelium and stroma, respectively, between tumor and normal tissue (ΔTumor − ΔBenign >2 versus ≤2), was predictive for clinical progression-free survival in the biopsy samples (P = 0.014). Preliminary results of this research show already a promising role of differential AR expression in predicting clinical relapse after PCa treatment with primary EBRT. Further research is needed to validate these findings. Hopefully this can lead to a better understanding of PCa evolution and eventually lead to better therapy strategies. Filip Poelaert, Charles Van Praet, Anne-Sophie Beerens, Gert De Meerleer, Valérie Fonteyne, Piet Ost, and Nicolaas Lumen Copyright © 2015 Filip Poelaert et al. All rights reserved. Impact of Different Body Positions on Bioelectrical Activity of the Pelvic Floor Muscles in Nulliparous Continent Women Sun, 22 Feb 2015 11:31:13 +0000 We examined pelvic floor muscles (PFM) activity (%MVC) in twenty nulliparous women by body position during exercise as well as the activation of abdominal muscles and the gluteus maximus during voluntary contractions of the PFMs. Pelvic floor muscle activity was recorded using a vaginal probe during five experimental trials. Activation of transversus abdominis, rectus abdominis, and gluteus maximus during voluntary PFM contractions was also assessed. Significant differences in mean normalized amplitudes of baseline PFM activity were revealed between standing and lying () and lying and ball-sitting positions (). Average peak, average time before peak, and average time after peak did not differ significantly during the voluntary contractions of the PFMs. Baseline PFM activity seemed to depend on the body position and was the highest in standing. Pelvic floor muscles activity during voluntary contractions did not differ by position in continent women. Statistically significant differences between the supine lying and sitting positions were only observed during a sustained 60-second contraction of the PFMs. Daria Chmielewska, Magdalena Stania, Grzegorz Sobota, Krystyna Kwaśna, Edward Błaszczak, Jakub Taradaj, and Grzegorz Juras Copyright © 2015 Daria Chmielewska et al. All rights reserved. Perineal Urethrostomy: Surgical and Functional Evaluation of Two Techniques Thu, 19 Feb 2015 11:56:55 +0000 Introduction. PU is an option to manage complex and/or recurrent urethral strictures and is necessary after urethrectomy and/or penectomy. PU is generally assumed to be the last option before abandoning the urethral outlet. Methods. Between 2001 and 2013, 51 patients underwent PU. Mean age (± standard deviation) was years. Only 13 patients (25.5%) did not undergo previous urethral interventions. PU was performed according to the Johanson or Blandy technique and these 2 groups were compared for surgical failure, maximum urinary flow (), urinary symptoms, and quality of life (according to the International Prostate Symptom Score). Results. Both groups were similar for patient’s and stricture characteristics. Only follow-up duration was significantly longer after Johanson PU (47.9 months versus 11.1 months; ). For the entire cohort, 11 patients (21.6%) were considered a failure (9 or 25.7% for Johanson group and 2 or 12.5% for Blandy group; ). There was a significant improvement of in both groups. Quality of life after PU was comparable in both groups. Conclusions. PU is associated with a 21.6% recurrence rate and the patient should be informed about this risk. Nicolaas Lumen, Matthias Beysens, Charles Van Praet, Karel Decaestecker, Anne-Francoise Spinoit, Piet Hoebeke, and Willem Oosterlinck Copyright © 2015 Nicolaas Lumen et al. All rights reserved. Sacrocolpopexy with Polypropylene Tape as Valuable Surgical Modification during Cystectomy with Orthotopic Ileal Bladder: Functional Results Thu, 19 Feb 2015 11:16:56 +0000 Introduction. Urinary diversion is very often associated with urinary retention and urinary incontinence. In this study, a surgical modification during cystectomy with orthotopic ileal neobladder is presented. Material and Methods. Female patients enrolled in the study (n-24) were subjected to sacrocolpopexy during the operation. Apart from oncological control, the follow-up consisted of 1-hour inlay test and questionnaires (UDI-6 and IIQ-7) in the 3rd, 6th, and 12th month after the operation. In the 12th month after the surgery, the urodynamic pressure-flow test was performed. Outcomes were compared with the control group (n-18) in which sacrocolpopexy was not implemented. Results. The study group was characterised by reduced urinary retention and improved continence. Conclusion. Sacrocolpopexy during cystectomy with orthotopic ileal bladder is a valuable surgical method which provides patients with a better quality of life. Marcin Życzkowski, Bartosz Muskała, Zbigniew Kaletka, Piotr Bryniarski, Krzysztof Nowakowski, Rafał Bogacki, and Andrzej Paradysz Copyright © 2015 Marcin Życzkowski et al. All rights reserved. Roles of Osteopontin Gene Polymorphism (rs1126616), Osteopontin Levels in Urine and Serum, and the Risk of Urolithiasis: A Meta-Analysis Sun, 15 Feb 2015 08:27:37 +0000 Objective. Previous studies have investigated the relationships between osteopontin gene polymorphism rs1126616 and OPN levels and urolithiasis, but the results were controversial. Our study aimed to clarify such relationships. Methods. A meta-analysis was performed by searching the databases Pubmed, Embase, and Web of Science for relevant studies. Crude odds ratios (ORs) or standardised mean differences with 95% confidence intervals (CIs) were calculated to evaluate the strength of association. Publication bias was estimated using Begg’s funnel plots and Egger’s regression test. Results. Overall, a significantly increased risk of urolithiasis was associated with OPN gene polymorphism rs1126616 for all the genetic models except recessive model. When stratified by ethnicity, the results were significant only in Turkish populations. For OPN level association, a low OPN level was detected in the urine of urolithiasis patients in large sample size subgroup. Results also indicated that urolithiasis patients have lower OPN level in serum than normal controls. Conclusion. This meta-analysis revealed that the T allele of OPN gene polymorphism increased susceptibility to urolithiasis. Moreover, significantly lower OPN levels were detected in urine and serum of urolithiasis patients than normal controls, thereby indicating that OPN has important functions in the progression of urolithiasis. Xiao Li, Kang Liu, Yongsheng Pan, Jing Zhang, Qiang Lv, Lixin Hua, Zengjun Wang, Jie Li, and Changjun Yin Copyright © 2015 Xiao Li et al. All rights reserved. Scaffolds from Surgically Removed Kidneys as a Potential Source of Organ Transplantation Tue, 10 Feb 2015 06:07:18 +0000 End stage renal disease (ESRD) is a common disease, which relates to nearly 600 million people in the total population. What is more, it seems to be a crucial problem from the epidemiological point of view. These facts lead to a further necessity of renal replacement therapy development connected with rising expenditures for the health care system. The aim of kidney tissue engineering is to develop and innovate methods of obtaining renal extracellular matrix (ECM) scaffolds derived from kidney decellularization. Recently, progress has been made towards developing a functional kidney graft in vitro on demand. In fact, decellularized tissues constitute ideal natural scaffolds, due to the preservation of native ECM architecture, as well as of cell-ECM binding domains critical in promoting cell attachment, migration, and proliferation. One of the potential sources of the natural scaffolds is the kidney, which cannot be transplanted immediately after excision. Marek Karczewski and Tomasz Malkiewicz Copyright © 2015 Marek Karczewski and Tomasz Malkiewicz. All rights reserved. Pathfast Presepsin Assay for Early Diagnosis of Systemic Inflammatory Response Syndrome in Patients with Nephrolithiasis Wed, 04 Feb 2015 09:26:37 +0000 It is relatively difficult to diagnose bacterial sepsis in nephrolithiasis patients. The aim of the study is to evaluate the diagnostic ability of presepsin in the differential diagnosis including SIRS, infection, or sepsis and to compare its diagnostic value with other markers, mainly as CRP, procalcitonin (PCT), and white blood cell (WBC) in patients of nephrolithiasis presenting with SIRS. 39 patients of nephrolithiasis who were diagnosed as SIRS were prospectively investigated. Plasma presepsin was detected by Pathfast presepsin assay system; CRP and PCT were measured as well. Additionally, 25 nephrolithiasis patients without SIRS were included. At all timing samples, patients were classified as SIRS or non-SIRS group. Median plasma presepsin levels were significantly increased in the SIRS group compared with non-SIRS group (452 pg/mL versus 178 ng/mL, ), and presepsin was markedly elevated even in the early stage of SIRS (584 pg/mL 6 h, 660 pg/mL 24 h versus 452 pg/mL, ). According to the receiver-operating characteristic (ROC) analysis, presepsin demonstrated a high diagnostic value compared with either PCT or CRP. In the early stage of SIRS, presepsin remained a highly sensitive (74.7%) and specific (88.4%) diagnostic marker compared with either PCT, CRP, or WBC. Moreover, the areas under the curve (AUCs) of presepsin (84.6%) were also superior to those seen in either PCT (79.6%) or CRP (71.8%). Thus plasma presepsin levels have comparable performance in SIRS for patients with nephrolithiasis. Yan-song Hou, Hua Wang, Hao Chen, Ling-feng Wu, Lin-feng Lu, and Yi He Copyright © 2015 Yan-song Hou et al. All rights reserved. Proinflammatory Cytokines in Prostate Cancer Development and Progression Promoted by High-Fat Diet Wed, 04 Feb 2015 06:24:16 +0000 Background. We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa) development and progression promoted by high-fat diet (HFD). Methods. TRAMP (transgenic adenocarcinoma mouse prostate) mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study. Results. A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33%) were from the normal diet group and 10 (27.78%) from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (). Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (). Proinflammatory cytokines levels, including IL-1α, IL-1β, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice. Conclusions. HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD. Hua Xu, Meng-bo Hu, Pei-de Bai, Wen-hui Zhu, Sheng-hua Liu, Jun-yao Hou, Zu-quan Xiong, Qiang Ding, and Hao-wen Jiang Copyright © 2015 Hua Xu et al. All rights reserved. The Potential Role of Polymethyl Methacrylate as a New Packaging Material for the Implantable Medical Device in the Bladder Sun, 01 Feb 2015 13:52:41 +0000 Polydimethylsiloxane (PDMS) is used in implantable medical devices; however, PDMS is not a completely biocompatible material for electronic medical devices in the bladder. To identify novel biocompatible materials for intravesical implanted medical devices, we evaluated the biocompatibility of polymethyl methacrylate (PMMA) by analyzing changes in the levels of macrophages, macrophage migratory inhibitory factor (MIF), and inflammatory cytokines in the bladder. A ball-shaped metal coated with PMMA or PDMS was implanted into the bladders of rats, and after intravesical implantation, the inflammatory changes induced by the foreign body reaction were evaluated. In the early period after implantation, increased macrophage activity and MIF in the urothelium of the bladder were observed. However, significantly decreased macrophage activity and MIF in the bladder were observed after implantation with PMMA- or PDMS-coated metal in the later period. In addition, significantly decreased inflammatory cytokines such as IL-1β, IL-6, and TNF-α were observed with time. Based on these results, we suggest that MIF plays a role in the foreign body reaction and in the biocompatible packaging with PMMA for the implanted medical devices in the bladder. Su Jin Kim, Bumkyoo Choi, Kang Sup Kim, Woong Jin Bae, Sung Hoo Hong, Ji Youl Lee, Tae-Kon Hwang, and Sae Woong Kim Copyright © 2015 Su Jin Kim et al. All rights reserved. The G Allele of CaSR R990G Polymorphism Increases Susceptibility to Urolithiasis and Hypercalciuria: Evidences from a Comprehensive Meta-Analysis Sun, 01 Feb 2015 12:23:33 +0000 Background. The calcium-sensing receptor gene (CaSR) is a candidate to explain urolithiasis. A number of case-control studies were conducted to investigate associations between CaSR polymorphisms with risks of hypercalciuria and urolithiasis in humans. But the results were still inconsistent. Methods. A meta-analysis was performed to address this issue. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations between CaSR polymorphisms and the risk of urolithiasis. The pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of CaSR polymorphisms and urine calcium concentration. Results. For urolithiasis association, the SS genotype of A986S polymorphism was a risk factor for urolithiasis in Asians and PHPT patients, but a protective factor in Caucasians. The GG genotype of R990 polymorphism was associated with an increased risk of urolithiasis, especially in Caucasians and healthy population. Regarding urine calcium concentration association, individuals with the G allele had a higher level of urine calcium than the noncarriers. Conclusions. This meta-analysis revealed that the G allele of CaSR R990G polymorphism increases susceptibility to urolithiasis and hypercalciuria. The A986S and Q1011E polymorphisms were associated with urolithiasis and hypercalciuria in specific populations. Kang Liu, Xiaolan Wang, Jiaxin Ye, Chao Qin, Pengfei Shao, Wei Zhang, Jie Li, and Changjun Yin Copyright © 2015 Kang Liu et al. All rights reserved. Salvage Pelvic Lymph Node Dissection in Recurrent Prostate Cancer: Surgical and Early Oncological Outcome Wed, 28 Jan 2015 09:46:50 +0000 Methodology. Seventeen patients with prostate-specific antigen (PSA) rise following local treatment for prostate cancer with curative intent underwent open or minimally invasive salvage pelvic lymph node dissection (SLND) for oligometastatic disease (<4 synchronous metastases) or as staging prior to salvage radiotherapy. Biochemical recurrence after complete biochemical response (cBR) was defined as 2 consecutive PSA increases >0,2 ng/mL; and after incomplete biochemical response as 2 consecutive PSA rises. Newly found metastasis on imaging defined clinical progression (CP). Palliative androgen deprivation therapy (ADT) was initiated if >3 metastases were detected or if patients became symptomatic. Kaplan-Meier statistics were applied. Results. Clavien-Dindo grade 1, 2, 3a, and 3b complications were seen in 6, 1, 1, and 2 patients, respectively. Median follow-up time was 22 months. Among 13 patients treated for oligometastatic disease, 8 (67%) had a PSA decline, with 3 patients showing cBR. Median PSA progression-free survival (FS) was 4.1 months and median CP-FS 7 months. Three patients started ADT, resulting in a 2-year ADT-FS rate of 79.5%. Conclusion. SLND is feasible, but postoperative complication rate seems higher than that for primary LND. Biochemical and clinical response duration is limited, but as part of an oligometastatic treatment regime it can defer palliative ADT. Tom Claeys, Charles Van Praet, Nicolaas Lumen, Piet Ost, Valérie Fonteyne, Gert De Meerleer, Bieke Lambert, Louke Delrue, Pieter De Visschere, Geert Villeirs, and Karel Decaestecker Copyright © 2015 Tom Claeys et al. All rights reserved. Effects of Adult Male Circumcision on Premature Ejaculation: Results from a Prospective Study in China Wed, 28 Jan 2015 08:34:34 +0000 The purpose of this study is to investigate the effects of adult male circumcision on premature ejaculation (PE). Therefore, between December 2009 and March 2014, a total of 575 circumcised men and 623 uncircumcised men (control group) were evaluated. Detailed evaluations (including circumcision and control groups) on PE were conducted before circumcision and at the 3-, 6-, 9-, and 12-month follow-up visits after circumcision. Self-estimated intravaginal ejaculatory latency time (IELT), Patient-Reported Outcome measures, and 5-item version of the International Index of Erectile Function were used to measure the ejaculatory and erectile function for all subjects. The results showed that, during the one-year follow-up, men after circumcision experienced higher IELT and better scores of control over ejaculation, satisfaction with sexual intercourse, and severity of PE than men before circumcision ( for all). Similarly, when compared with the control group, the circumcised men reported significantly improved IELT, control over ejaculation, and satisfaction with sexual intercourse ( for all). These findings suggested that circumcision might have positive effects on IELT, ejaculatory control, sexual satisfaction, and PE severity. In addition, circumcision was significantly associated with the development of PE. Jingjing Gao, Chuan Xu, Jingjing Zhang, Chaozhao Liang, Puyu Su, Zhen Peng, Kai Shi, Dongdong Tang, Pan Gao, Zhaoxiang Lu, Jishuang Liu, Lei Xia, Jiajia Yang, Zongyao Hao, Jun Zhou, and Xiansheng Zhang Copyright © 2015 Jingjing Gao et al. All rights reserved. MRI-Targeted Biopsies versus Systematic Transrectal Ultrasound Guided Biopsies for the Diagnosis of Localized Prostate Cancer in Biopsy Naïve Men Tue, 27 Jan 2015 11:38:42 +0000 Introduction. To compare, in the same cohort of men, the detection of clinically significant disease in standard (STD) cores versus multiparametric magnetic resonance imaging (mpMRI) targeted (TAR) cores. Material and Methods. A prospective study was conducted on 129 biopsy naïve men with clinical suspicion of prostate cancer. These patients underwent prebiopsy mpMRI with STD systematic biopsies and TAR biopsies when lesions were found. The agreement between the TAR and the STD protocols was measured using Cohen’s kappa coefficient. Results. Cancer detection rate of MRI-targeted biopsy was 62.7%. TAR protocol demonstrated higher detection rate of clinically significant disease compared to STD protocol. The proportion of cores positive for clinically significant cancer in TAR cores was 28.9% versus 9.8% for STD cores (). The proportion of men with clinically significant cancer and the proportion of men with Gleason score 7 were higher with the TAR protocol than with the STD protocol (; , resp.). Conclusion. mpMRI improved clinically significant prostate cancer detection rate compared to STD protocol alone with less tissue sampling and higher Gleason score. Further development in imaging as well as multicentre studies using the START recommendation is needed to elucidate the role of mpMRI targeted biopsy in the management of prostate cancer. Alexandre Peltier, Fouad Aoun, Marc Lemort, Félix Kwizera, Marianne Paesmans, and Roland Van Velthoven Copyright © 2015 Alexandre Peltier et al. All rights reserved. CTLA4 Polymorphisms and De Novo Malignancy Risk after Renal Transplantation in Chinese Recipients Thu, 15 Jan 2015 13:49:12 +0000 Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4) play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of five CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with de novo malignancy in 1463 Chinese renal transplantation (RT) recipients who underwent a 192-month follow-up. Multivariate analyses revealed that recipient rs231775 genotype is significantly associated with tumorigenesis (). Multiplicative interaction between rs231775 AA and possible risk factors of malignancy revealed two significant results: rs231775 AA × primary diseases and rs231775 AA × number of HLA-mismatch. The frequency of haplotype TACAG was significantly higher in the tumor group (17.07%) than that in the nontumor group (1.53%). In addition, aristolochic acid nephropathy () and the time of discovery of tumor () also were independently associated with tumorigenesis. Our data show that the CTLA4 genotype rs231775 AA may be one of risk factors for the development of malignancy and haplotype TACAG was susceptible haplotype in Chinese kidney transplant recipients. Yi-feng Guo, Jian-xin Qiu, Fang Guo, Yong Liu, and Ming-hua Shang Copyright © 2015 Yi-feng Guo et al. All rights reserved. Biomarker and Translational Prostate Cancer Research Thu, 15 Jan 2015 12:30:36 +0000 Andreas Doll, Jeremy Clark, and Colleen Nelson Copyright © 2015 Andreas Doll et al. All rights reserved. Identification and Validation of Potential New Biomarkers for Prostate Cancer Diagnosis and Prognosis Using 2D-DIGE and MS Thu, 15 Jan 2015 11:16:51 +0000 This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 ( < 0.044) in prostate cancer, while vinculin showed significant upregulation ( < 0.001). Secernin-1 overexpression in prostate tissue was validated using Western blot and immunohistochemistry while vinculin expression was validated using immunohistochemistry. These findings indicate that secernin-1 and vinculin are potential new tissue biomarkers for prostate cancer diagnosis and prognosis, respectively. For validation, protein levels in urine were also examined by Western blot analysis. Urinary vinculin levels in prostate cancer patients were significantly higher than in urine from nontumor patients ( = 0.006). Using multiple reaction monitoring-MS (MRM-MS) analysis, prostatic acid phosphatase (PAP) showed significant higher levels in the urine of prostate cancer patients compared to controls ( = 0.012), while galectin-3 showed significant lower levels in the urine of prostate cancer patients with biochemical relapse, compared to those without relapse ( = 0.017). Three proteins were successfully differentiated between patients with and without prostate cancer and patients with and without relapse by using MRM. Thus, this technique shows promise for implementation as a noninvasive clinical diagnostic technique. Cordelia Geisler, Nadine T. Gaisa, David Pfister, Susanne Fuessel, Glen Kristiansen, Till Braunschweig, Sonja Gostek, Birte Beine, Hanna C. Diehl, Angela M. Jackson, Christoph H. Borchers, Axel Heidenreich, Helmut E. Meyer, Ruth Knüchel, and Corinna Henkel Copyright © 2015 Cordelia Geisler et al. All rights reserved. Carcinoma In Situ Is Significantly Underdetected by Prenephroureterectomy Ureteroscopy in the Management of Upper Tract Urothelial Cancers Thu, 15 Jan 2015 08:10:36 +0000 Objective. Diagnostic reliability of prenephroureterectomy ureteroscopy (PNU) for the detection of upper tract carcinoma in situ (CIS) remains unproven in particular and underreported in general. Methods. Patients who underwent radical nephroureterectomy (RNU) in a large multicentre retrospective study for upper tract transitional cell carcinoma (UT-TCC) between January 2002 and December 2013 were identified from our hospitals databases. PNU appearances, stage, and grade of ureteroscopic biopsy were compared with final histology results of RNU to assess the diagnostic reliability of PNU for carcinoma in situ (CIS). Results. Three hundred patients underwent RNU for UT-TCC. 106 (106/300; 35.3%) of the cohort had PNU using white light with biopsies taken in most (92/106; 86.7%). Postnephroureterectomy histology of the cohort showed CIS in 65 (65/300; 21.6%) patients. Thirty nine of patients with CIS (39/65; 60%) had prenephroureterectomy ureteroscopy biopsies. Out of ten patients with CIS on ureteroscopic biopsies, six did not show CIS on final histopathology (6/10; 60%). Moreover, grading and staging on PNU biopsies of obvious tumours showed a significant nonconcordance with final histopathology of RNU specimen . Overall survival was also shorter in patients with CIS compared with those without; this showed strong statistical significance . Conclusions. There is a high incidence of CIS in upper tract with significant underdetection and discordance rate between the histopathology of biopsy samples obtained by white light PNU and resected specimen of radical nephroureterectomy. The presence of concomitant CIS and high stage disease in the upper tract TCC carried a poor prognosis following radical nephroureterectomy. Angela Gillan, Ismail El-Mokadem, Bhavan Rai, Stephen Lang, Jason Alcorn, Altaf Shams ud din, Ranan Dasgupta, Chandra Shekhar Biyani, and Ghulam Nabi Copyright © 2015 Angela Gillan et al. All rights reserved. Superficial Tunica Albuginea Rupture as Initial Starting Point of Peyronie’s Disease: A Topic for Interdisciplinary Consideration Thu, 15 Jan 2015 07:48:04 +0000 Peyronie’s disease is a connective tissue disorder in the soft tissue of the penis. The underlying cause of Peyronie’s disease is not well understood but is thought to be caused by trauma or injury to the penis during sexual intercourse. The purpose of the interdisciplinary cooperation between urological surgery and physics is the development of a physical simulation tool in order to give prognosis of possible tunica albuginea fibre rupture at a certain degree of deviation of the penis. For our group the first challenge was to translate the human organ of the penis into a physical model. Starting and marginal parameters had to be defined, whereby some of them had to be based on assumption, as physical data of the human living tissue have rarely been measured up to now. The algorithm and its dependencies had to be developed. This paper is a first step of a three-dimensional mathematical-physical simulation with the assumption of a 100% filled rigid penis. The calculation gives proof of the hypothesis that the fibre-load-angle of the penis is less than 12 degrees. Thus physical simulation is able to provide the surgeon with a simple instrument to calculate and forecast the risk of the individual patient. Ralf Herwig and Manfred Bayerl Copyright © 2015 Ralf Herwig and Manfred Bayerl. All rights reserved. A Rare Emergency: Testicular Torsion in the Inguinal Canal Wed, 14 Jan 2015 13:56:34 +0000 Objectives. To report our experience and present the largest series of testicular torsion cases in the inguinal canal. Material and Methods. The clinical data of 13 patients with testicular torsion in the inguinal canal treated between 2005 and 2013 were reviewed. Recorded patient age, whether the testes were palpable or not, side of the affected testes, the presence of hernia, ischemia time, and operation outcomes were assessed. Results. Patient age ranged from 8 to 70 months (29.15 ± 20.22). Mean ischemia time was 16.5 ± 21.3 hours. Accompanying inguinal hernia was present in 92% of the cases (12/13). Four of the thirteen patients (30.8%) were treated by orchiectomy because the necrosis was present after prolonged ischemia time. Nine patients (69.2%) were treated by single session orchidopexy. Conclusion. Torsion of testes in the inguinal canal is a rare disease, but with rapid diagnosis, affected testes can be salvaged, but the key factor is to keep this condition in mind. Nevzat Can Şener, Okan Bas, Nihat Karakoyunlu, Hakan Ercil, Suleyman Yesil, Kursad Zengin, and Abdurrahim Imamoglu Copyright © 2015 Nevzat Can Şener et al. All rights reserved. Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines Mon, 12 Jan 2015 09:39:54 +0000 Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812), ). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155), ) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939), ) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence. M. Olivan, M. Rigau, E. Colás, M. Garcia, M. Montes, T. Sequeiros, L. Regis, A. Celma, J. Planas, J. Placer, J. Reventós, I. de Torres, A. Doll, and J. Morote Copyright © 2015 M. Olivan et al. All rights reserved. Preparation and Characterization of Gelatin-Based Mucoadhesive Nanocomposites as Intravesical Gene Delivery Scaffolds Mon, 15 Dec 2014 00:11:02 +0000 This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as scaffolds for intravesical gene delivery to the urothelium. Hydrogels were prepared by chemically crosslinking gelatin A or B with glutaraldehyde. Physicochemical and delivery properties including hydration ratio, viscosity, size, yield, thermosensitivity, and enzymatic degradation were studied, and scanning electron microscopy (SEM) was carried out. The optimal hydrogels (H), composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration ratio, 42.9 Pa·s viscosity, and 125.8 nm particle size. The crosslinking density of the hydrogels was determined by performing pronase degradation and ninhydrin assays. In vitro lentivirus (LV) release studies involving p24 capsid protein analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV) had a higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3-fold at days 1, 3, and 5, resp.). Lentivirus from lentivector constructed green fluorescent protein (GFP) was then entrapped in hydrogels (H-LV-GFP). H-LV-GFP showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV reduced peak micturition and threshold pressure and increased bladder compliance. In this study, we successfully developed first optimal gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds. Ching-Wen Liu, Li-Ching Chang, Kai-Jen Lin, Tsan-Jung Yu, Ching-Chung Tsai, Hao-Kuang Wang, and Tong-Rong Tsai Copyright © 2014 Ching-Wen Liu et al. All rights reserved. Final Gleason Score Prediction Using Discriminant Analysis and Support Vector Machine Based on Preoperative Multiparametric MR Imaging of Prostate Cancer at 3T Tue, 02 Dec 2014 10:38:21 +0000 Objective. This study aimed at evaluating linear discriminant analysis (LDA) and support vector machine (SVM) classifiers for estimating final Gleason score preoperatively using multiparametric magnetic resonance imaging (mp-MRI) and clinical parameters. Materials and Methods. Thirty-three patients who underwent mp-MRI on a 3T clinical MR scanner and radical prostatectomy were enrolled in this study. The input features for classifiers were age, the presence of a palpable prostate abnormality, prostate specific antigen (PSA) level, index lesion size, and Likert scales of T2 weighted MRI (T2w-MRI), diffusion weighted MRI (DW-MRI), and dynamic contrast enhanced MRI (DCE-MRI) estimated by an experienced radiologist. SVM based recursive feature elimination (SVM-RFE) was used for eliminating features. Principal component analysis (PCA) was applied for data uncorrelation. Results. Using a standard PCA before final Gleason score classification resulted in mean sensitivities of 51.19% and 64.37% and mean specificities of 72.71% and 39.90% for LDA and SVM, respectively. Using a Gaussian kernel PCA resulted in mean sensitivities of 86.51% and 87.88% and mean specificities of 63.99% and 56.83% for LDA and SVM, respectively. Conclusion. SVM classifier resulted in a slightly higher sensitivity but a lower specificity than LDA method for final Gleason score prediction for prostate cancer for this limited patient population. Fusun Citak-Er, Metin Vural, Omer Acar, Tarik Esen, Aslihan Onay, and Esin Ozturk-Isik Copyright © 2014 Fusun Citak-Er et al. All rights reserved. Multiparametric MRI in Prostate Cancer Mon, 01 Dec 2014 12:19:02 +0000 Tarık Esen, Barıs Turkbey, Anup Patel, and Jurgen Futterer Copyright © 2014 Tarık Esen et al. All rights reserved. Conspicuity of Peripheral Zone Prostate Cancer on Computed Diffusion-Weighted Imaging: Comparison of cDWI1500, cDWI2000, and cDWI3000 Mon, 01 Dec 2014 11:13:22 +0000 Introduction and Objective. Disadvantages associated with direct high b-value measurements may be avoided with use of computed diffusion-weighted imaging (cDWI). The purpose of this study is to assess the diagnostic performance of cDWI image sets calculated for high b-values of 1500, 2000, and 3000 s/mm2. Materials and Methods. Twenty-eight patients who underwent multiparametric MRI of the prostate and radical prostatectomy consecutively were enrolled in this retrospective study. Using a software developed at our institute, cDWI1500, cDWI2000, and cDWI3000 image sets were generated by fitting a monoexponential model. Index lesions on cDWI image sets were scored by two radiologists in consensus considering lesion conspicuity, suppression of background prostate tissue, distortion, image set preferability, and contrast ratio measurements were performed. Results. Lesion detection rates are the same for computed b-values of 2000 and 3000 s/mm2 and are better than b-values of 1500 s/mm2. Best lesion conspicuity and best background prostate tissue suppression are provided by cDWI3000 image set. cDWI2000 image set provides the best zonal anatomical delineation and less distortion and was chosen as the most preferred image set. Average contrast ratio measured on these image sets shows almost a linear relation with the b-values. Conclusion. cDWI2000 image set with similar conspicuity and the same lesion detection rate, but better zonal anatomical delineation, and less distortion, was chosen as the preferable image set. Metin Vural, Gökhan Ertaş, Aslıhan Onay, Ömer Acar, Tarık Esen, Yeşim Sağlıcan, Hale Pınar Zengingönül, and Sergin Akpek Copyright © 2014 Metin Vural et al. All rights reserved. Computer Aided-Diagnosis of Prostate Cancer on Multiparametric MRI: A Technical Review of Current Research Mon, 01 Dec 2014 09:11:32 +0000 Prostate cancer (PCa) is the most commonly diagnosed cancer among men in the United States. In this paper, we survey computer aided-diagnosis (CADx) systems that use multiparametric magnetic resonance imaging (MP-MRI) for detection and diagnosis of prostate cancer. We review and list mainstream techniques that are commonly utilized in image segmentation, registration, feature extraction, and classification. The performances of 15 state-of-the-art prostate CADx systems are compared through the area under their receiver operating characteristic curves (AUC). Challenges and potential directions to further the research of prostate CADx are discussed in this paper. Further improvements should be investigated to make prostate CADx systems useful in clinical practice. Shijun Wang, Karen Burtt, Baris Turkbey, Peter Choyke, and Ronald M. Summers Copyright © 2014 Shijun Wang et al. All rights reserved. Multiparametric MRI-Targeted TRUS Prostate Biopsies Using Visual Registration Mon, 01 Dec 2014 06:44:57 +0000 Prebiopsy multiparametric prostate MRI (mp-MRI), followed by transrectal ultrasound-guided (TRUS-G) target biopsies (TB) of the prostate is a key combination for the diagnosis of clinically significant prostate cancers (CSPCa), to avoid prostate cancer (PCa) overtreatment. Several techniques are available for guiding TB to the suspicious mp-MRI targets, but the simplest, cheapest, and easiest to learn is “cognitive,” with visual registration of MRI and TRUS data. This review details the successive steps of the method (target detection, mp-MRI reporting, intermodality fusion, TRUS guidance to target, sampling simulation, sampling, TRUS session reporting, and quality insurance), how to optimize each, and the global indications of mp-MRI-targeted biopsies. We discuss the diagnostic yield of visually-registered TB in comparison with conventional biopsy, and TB performed using other registration methods. Philippe Puech, Adil Ouzzane, Vianney Gaillard, Nacim Betrouni, Benoit Renard, Arnauld Villers, and Laurent Lemaitre Copyright © 2014 Philippe Puech et al. All rights reserved. Multiparametric MRI for Localized Prostate Cancer: Lesion Detection and Staging Sun, 30 Nov 2014 14:02:49 +0000 Multiparametric MRI of the prostate combines high-resolution anatomic imaging with functional imaging of alterations in normal tissue caused by neoplastic transformation for the identification and characterization of in situ prostate cancer. Lesion detection relies on a systematic approach to the analysis of both anatomic and functional imaging using established criteria for the delineation of suspicious areas. Staging includes visual and functional analysis of the prostate “capsule” to determine if in situ disease is, in fact, organ-confined, as well as the evaluation of pelvic structures including lymph nodes and bones for the detection of metastasis. Although intertwined, the protocol can be optimized depending on whether lesion detection or staging is of the highest priority. Daniel J. A. Margolis Copyright © 2014 Daniel J. A. Margolis. All rights reserved. The Role of MRI in Prostate Cancer Active Surveillance Sun, 30 Nov 2014 13:07:19 +0000 Prostate cancer is the most common cancer diagnosis in American men, excluding skin cancer. The clinical behavior of prostate cancer varies from low-grade, slow growing tumors to high-grade aggressive tumors that may ultimately progress to metastases and cause death. Given the high incidence of men diagnosed with prostate cancer, conservative treatment strategies such as active surveillance are critical in the management of prostate cancer to reduce therapeutic complications of radiation therapy or radical prostatectomy. In this review, we will review the role of multiparametric MRI in the selection and follow-up of patients on active surveillance. Linda M. Johnson, Peter L. Choyke, William D. Figg, and Baris Turkbey Copyright © 2014 Linda M. Johnson et al. All rights reserved. A Comprehensive Review of Contemporary Role of Local Treatment of the Primary Tumor and/or the Metastases in Metastatic Prostate Cancer Mon, 17 Nov 2014 06:46:22 +0000 To provide an overview of the currently available literature regarding local control of primary tumor and oligometastases in metastatic prostate cancer and salvage lymph node dissection of clinical lymph node relapse after curative treatment of prostate cancer. Evidence Acquisition. A systematic literature search was conducted in 2014 to identify abstracts, original articles, review articles, research articles, and editorials relevant to the local control in metastatic prostate cancer. Evidence Synthesis. Local control of primary tumor in metastatic prostate cancer remains experimental with low level of evidence. The concept is supported by a growing body of genetic and molecular research as well as analogy with other cancers. There is only one retrospective observational population based study showing prolonged survival. To eradicate oligometastases, several options exist with excellent local control rates. Stereotactic body radiotherapy is safe, well tolerated, and efficacious treatment for lymph node and bone lesions. Both biochemical and clinical progression are slowed down with a median time to initiate ADT of 2 years. Salvage lymph node dissection is feasible in patients with clinical lymph node relapse after local curable treatment. Conclusion. Despite encouraging oncologic midterm results, a complete cure remains elusive in metastatic prostate cancer patients. Further advances in imaging are crucial in order to rapidly evolve beyond the proof of concept. Fouad Aoun, Alexandre Peltier, and Roland van Velthoven Copyright © 2014 Fouad Aoun et al. All rights reserved. Prepubertal Exposure to Genistein Alleviates Di-(2-ethylhexyl) Phthalate Induced Testicular Oxidative Stress in Adult Rats Wed, 29 Oct 2014 08:15:33 +0000 Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors. Lian-Dong Zhang, He-Cheng Li, Tie Chong, Ming Gao, Jian Yin, De-Lai Fu, Qian Deng, and Zi-Ming Wang Copyright © 2014 Lian-Dong Zhang et al. All rights reserved. Identification of Endothelial Progenitor Cells in the Corpus Cavernosum in Rats Tue, 21 Oct 2014 00:00:00 +0000 The vascular wall resident progenitor cells seem to serve as a local reservoir of cells for vascular repair. It was hypothesized that the corpus cavernosum may contain vascular wall endothelial progenitor cells (EPCs). In this study, we investigated the identification and localization of EPCs in the corpus cavernosum in a rat model. Adult male Sprague-Dawley rats were used to isolate EPCs from corpora cavernosum. To verify the existence and localization of EPCs, EPC-specific markers (CD34, Flk-1, and VE-cadherin) were evaluated by flow cytometric analysis and confocal microscopy. The EPC markers were mainly expressed in the cavernosal sinusoidal endothelial space. EPC-marker-positive cells made up about 3.31% of the corpus cavernosum of normal rat by FACS analysis. As shown by confocal microscopy, CD34+/Flk-1+ and CD34+/VE-cadherin+ positive cells existed in the corpus cavernosum. Our findings imply that regulation of corpus cavernosal EPCs may be a new therapeutic strategy in the treatment of erectile dysfunction. Jun Sik Lee, In Sang Hwang, Hyun-Suk Lee, Mi Eun Kim, Young-Woo Seo, and Kwangsung Park Copyright © 2014 Jun Sik Lee et al. All rights reserved. Coating of Mesh Grafts for Prolapse and Urinary Incontinence Repair with Autologous Plasma: Exploration Stage of a Surgical Innovation Tue, 16 Sep 2014 07:57:09 +0000 Purpose. Optimized biocompatibility is a major requirement for alloplastic materials currently applied for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) repair. In the preliminary studies the mesh modification by coating with autologous plasma resulted in the increased adherence score in vitro and improved biocompatibility in an animal model. The first use of plasma coated meshes in human is presented. Materials and Methods. Between 04/2013 and 05/2014, 20 patients with the indication for SUI and POP repair were selected in a single institution. The applied meshes were modified by autologous plasma coating prior to implantation. A retrospective chart review for peri- and early postoperative complications was performed. Functional outcome and QoL were evaluated pre- and postoperatively. Results. The functional outcome and QoL improved significantly in all groups. Two reoperations (Grade IIIB) with the release of TVT-mesh in anesthesia due to the obstruction were needed. No other severe complications were registered. Conclusion. For the first time we applied a mesh modification in a human setting according to IDEAL criteria of surgical innovations. The procedure of mesh coating with autologous plasma is safe and a prospective randomized trial proving a positive effect of plasma coating on the biocompatibility and morbidity outcome with long-term registry is planned. Dimitri Barski, Holger Gerullis, Evangelos Georgas, Andreas Bär, Bernhard Lammers, Albert Ramon, Dirk Ysebaert, Bernd Klosterhalfen, Mihaly Boros, and Thomas Otto Copyright © 2014 Dimitri Barski et al. All rights reserved. A Comparison of Antegrade Percutaneous and Laparoscopic Approaches in the Treatment of Proximal Ureteral Stones Thu, 11 Sep 2014 06:29:06 +0000 Purpose. To compare the effectiveness and safety of retroperitoneal laparoscopic ureterolithotomy (RLU) and percutaneous antegrade ureteroscopy (PAU) in which we use semirigid ureteroscopy in the treatment of proximal ureteral stones. Methods. Fifty-eight patients with large, impacted stones who had a history of failed shock wave lithotripsy (SWL) and, retrograde ureterorenoscopy (URS) were included in the study between April 2007 and April 2014. Thirty-seven PAU and twenty-one RLU procedures were applied. Stone-free rates, operation times, duration of hospital stay, and follow-up duration were analyzed. Results. Overall stone-free rate was 100% for both groups. There was no significant difference between both groups with respect to postoperative duration of hospital stay and urinary leakage of more than 2 days. PAU group had a greater amount of blood loss (mean hemoglobin drops for PAU group and RLU group were 1.6 ± 1.1 g/dL versus 0.5 ± 0.3 g/dL, resp.; ). RLU group had longer operation time (for PAU group and RLU group 80.1 ± 44.6 min versus 102.1 ± 45.5 min, resp.; ). Conclusions. Both PAU and RLU appear to be comparable in the treatment of proximal ureteral stones when the history is notable for a failed retrograde approach or SWL. The decision should be based on surgical expertise and availability of surgical equipment. Hikmet Topaloglu, Nihat Karakoyunlu, Sercan Sari, Hakki Ugur Ozok, Levent Sagnak, and Hamit Ersoy Copyright © 2014 Hikmet Topaloglu et al. All rights reserved. From Bench to Bedside: Immunotherapy for Prostate Cancer Thu, 04 Sep 2014 00:00:00 +0000 The mainstay therapeutic strategy for metastatic castrate-resistant prostate cancer (CRPC) continues to be androgen deprivation therapy usually in combination with chemotherapy or androgen receptor targeting therapy in either sequence, or recently approved novel agents such as Radium 223. However, immunotherapy has also emerged as an option for the treatment of this disease following the approval of sipuleucel-T by the FDA in 2010. Immunotherapy is a rational approach for prostate cancer based on a body of evidence suggesting these cancers are inherently immunogenic and, most importantly, that immunological interventions can induce protective antitumour responses. Various forms of immunotherapy are currently being explored clinically, with the most common being cancer vaccines (dendritic-cell, viral, and whole tumour cell-based) and immune checkpoint inhibition. This review will discuss recent clinical developments of immune-based therapies for prostate cancer that have reached the phase III clinical trial stage. A perspective of how immunotherapy could be best employed within current treatment regimes to achieve most clinical benefits is also provided. Brian Wan-Chi Tse, Lidija Jovanovic, Colleen Coyne Nelson, Paul de Souza, Carl Andrew Power, and Pamela Joan Russell Copyright © 2014 Brian Wan-Chi Tse et al. All rights reserved. Role of miRNA Let-7 and Its Major Targets in Prostate Cancer Wed, 03 Sep 2014 06:32:18 +0000 Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA) is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNA let-7 family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias. Siegfried Wagner, Anaclet Ngezahayo, Hugo Murua Escobar, and Ingo Nolte Copyright © 2014 Siegfried Wagner et al. All rights reserved. Traumatic Penile Injury: From Circumcision Injury to Penile Amputation Thu, 28 Aug 2014 08:48:46 +0000 The treatment of external genitalia trauma is diverse according to the nature of trauma and injured anatomic site. The classification of trauma is important to establish a strategy of treatment; however, to date there has been less effort to make a classification for trauma of external genitalia. The classification of external trauma in male could be established by the nature of injury mechanism or anatomic site: accidental versus self-mutilation injury and penis versus penis plus scrotum or perineum. Accidental injury covers large portion of external genitalia trauma because of high prevalence and severity of this disease. The aim of this study is to summarize the mechanism and treatment of the traumatic injury of penis. This study is the first review describing the issue. Jae Heon Kim, Jae Young Park, and Yun Seob Song Copyright © 2014 Jae Heon Kim et al. All rights reserved. Noncoding RNAs as Novel Biomarkers in Prostate Cancer Thu, 28 Aug 2014 07:21:42 +0000 Prostate cancer (PCa) is the second most common diagnosed malignant disease in men worldwide. Although serum PSA test dramatically improved the early diagnosis of PCa, it also led to an overdiagnosis and as a consequence to an overtreatment of patients with an indolent disease. New biomarkers for diagnosis, prediction, and monitoring of the disease are needed. These biomarkers would enable the selection of patients with aggressive or progressive disease and, hence, would contribute to the implementation of individualized therapy of the cancer patient. Since the FDA approval of the long noncoding PCA3 RNA-based urine test for the diagnosis of PCa patients, many new noncoding RNAs (ncRNAs) associated with PCa have been discovered. According to their size and function, ncRNAs can be divided into small and long ncRNAs. NcRNAs are expressed in (tumor) tissue, but many are also found in circulating tumor cells and in all body fluids as protein-bound or incorporated in extracellular vesicles. In these protected forms they are stable and so they can be easily analyzed, even in archival specimens. In this review, the authors will focus on ncRNAs as novel biomarker candidates for PCa diagnosis, prediction, prognosis, and monitoring of therapeutic response and discuss their potential for an implementation into clinical practice. C. G. H. Rönnau, G. W. Verhaegh, M. V. Luna-Velez, and J. A. Schalken Copyright © 2014 C. G. H. Rönnau et al. All rights reserved. Novel RNA Markers in Prostate Cancer: Functional Considerations and Clinical Translation Thu, 28 Aug 2014 00:00:00 +0000 The availability of ultra-high throughput DNA and RNA sequencing technologies in recent years has led to the identification of numerous novel transcripts, whose functions are unknown as yet. Evidence is accumulating that many of these molecules are deregulated in diseases, including prostate cancer, and potentially represent novel targets for diagnosis and therapy. In particular, functional genomic analysis of microRNA (miRNA) and long noncoding RNA (lncRNA) in cancer is likely to contribute insights into tumor development. Here, we compile recent efforts to catalog differential expression of miRNA and lncRNA in prostate cancer and to understand RNA function in tumor progression. We further highlight technologies for molecular characterization of noncoding RNAs and provide an overview of current activities to exploit them for the diagnosis and therapy of this complex tumor. Julia M. A. Pickl, Doreen Heckmann, Leonie Ratz, Sabine M. Klauck, and Holger Sültmann Copyright © 2014 Julia M. A. Pickl et al. All rights reserved. Prognostic Histopathological and Molecular Markers on Prostate Cancer Needle-Biopsies: A Review Wed, 27 Aug 2014 12:48:53 +0000 Prostate cancer is diverse in clinical presentation, histopathological tumor growth patterns, and survival. Therefore, individual assessment of a tumor’s aggressive potential is crucial for clinical decision-making in men with prostate cancer. To date a large number of prognostic markers for prostate cancer have been described, most of them based on radical prostatectomy specimens. However, in order to affect clinical decision-making, validation of respective markers in pretreatment diagnostic needle-biopsies is essential. Here, we discuss established and promising histopathological and molecular parameters in diagnostic needle-biopsies. A. Marije Hoogland, Charlotte F. Kweldam, and Geert J. L. H. van Leenders Copyright © 2014 A. Marije Hoogland et al. All rights reserved. Multiparametric MRI in the PSA Screening Era Wed, 27 Aug 2014 12:31:30 +0000 Prostate cancer remains significant public health concern amid growing controversies regarding prostate specific antigen (PSA) based screening. The utility of PSA has been brought into question, and alternative measures are investigated to remedy the overdetection of indolent disease and safeguard patients from the potential harms resulting from an elevated PSA. Multiparametric MRI of the prostate has shown promise in identifying patients at risk for clinically significant disease but its role within the current diagnostic and treatment paradigm remains in question. The current review focuses on recent applications of MRI in this pathway. Arvin K. George, Peter A. Pinto, and Soroush Rais-Bahrami Copyright © 2014 Arvin K. George et al. All rights reserved. Anatomic Imaging of the Prostate Wed, 27 Aug 2014 00:00:00 +0000 The important role of magnetic resonance imaging (MRI) in the anatomic evaluation, detection, and staging of prostate cancer is well established. This paper focuses on the pertinent embryologic, anatomic, and imaging facts regarding both the normal prostate and the several examples of prostate cancers as well as staging implications. The discussion primarily includes findings related to T2-weighted imaging as opposed to the other functional sequences, including diffusion weighted imaging (DWI) or dynamic contrast enhanced MRI and MR spectroscopic imaging, respectively. Anil Bhavsar and Sadhna Verma Copyright © 2014 Anil Bhavsar and Sadhna Verma. All rights reserved. Elevated Levels of miR-155 in Blood and Urine from Patients with Nephrolithiasis Thu, 14 Aug 2014 06:46:02 +0000 Background. Both circulating and urinary miRNAs may represent a potential noninvasive molecular biomarker capable of predicting chronic kidney disease, and, in the present study, we will investigate the serum and urinary levels of miR-155 in patients with nephrolithiasis. Methods. Serum and urinary levels of miR-155 are quantified in 60 patients with nephrolithiasis; the result was compared to 50 healthy volunteers. Estimated glomerular filtration (eGFR) was calculated and, by simple regression analysis, the correlations of miR-155/eGFR and miR-155/CRP (C-reactive protein) levels were analyzed as well. Results. The median levels of serum and urinary levels of miR-155 are significantly higher in nephrolithiasis patients than in controls. eGFR inversely correlates with urinary level of miR-155; CRP positively correlates with urinary miR-155. Urinary level of miR-155 inversely correlates with urinary expression of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α and positively correlates with urinary expression of regulated upon activation, normal T-cell expressed, and secreted (RANTES). Conclusion. Serum and urinary levels of miR-155 were significantly elevated in patients with nephrolithiasis, and the upregulation of miR-155 was correlated with decline of eGFR and elevation of CRP. Our results suggested that miR-155 might play important roles in the pathophysiology of nephrolithiasis via regulating inflammatory cytokines expression. Further study on the molecular pathogenic mechanism and larger scale of clinical trial are required. Yang-Yang Hu, Wei-Da Dong, Yun-Fei Xu, Xu-Dong Yao, Bo Peng, Min Liu, and Jun-Hua Zheng Copyright © 2014 Yang-Yang Hu et al. All rights reserved. The Role of Intrinsic Pathway in Apoptosis Activation and Progression in Peyronie’s Disease Wed, 13 Aug 2014 09:13:53 +0000 Peyronie’s disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes, and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplastic bone tissue. Apoptosis occurs in stabilized PD plaques and is partly induced by the intrinsic pathway. Carla Loreto, Giampiero La Rocca, Rita Anzalone, Rosario Caltabiano, Giuseppe Vespasiani, Sergio Castorina, David J. Ralph, Selim Cellek, Giuseppe Musumeci, Salvatore Giunta, Rados Djinovic, Dragoslav Basic, and Salvatore Sansalone Copyright © 2014 Carla Loreto et al. All rights reserved. Signalling Molecules in the Urothelium Sun, 10 Aug 2014 12:30:33 +0000 The urothelium was long considered to be a silent barrier protecting the body from the toxic effects of urine. However, today a number of dynamic abilities of the urothelium are well recognized, including its ability to act as a sensor of the intravesical environment. During recent years several pathways of these urothelial abilities have been proposed and a major part of these pathways includes release of signalling molecules. It is now evident that the urothelium represents only one part of the sensory web. Urinary bladder signalling is finely tuned machinery of signalling molecules, acting in autocrine and paracrine manner, and their receptors are specifically distributed among different types of cells in the urinary bladder. In the present review the current knowledge of the formation, release, and signalling effects of urothelial acetylcholine, ATP, adenosine, and nitric oxide in health and disease is discussed. Michael Winder, Gunnar Tobin, Daša Zupančič, and Rok Romih Copyright © 2014 Michael Winder et al. All rights reserved. Venous Ligation: A Novel Strategy for Glans Enhancement in Penile Prosthesis Implantation Thu, 07 Aug 2014 00:00:00 +0000 Although penile implantation remains a final solution for patients with refractory impotence, undesirable postoperative effects, including penile size reduction and cold sensation of the glans penis, remain problematic. We report results of a surgical method designed to avoid these problems. From 2003 to 2013, 35 consecutive patients received a malleable penile implant. Of these, 15 men (the enhancing group) were also treated with venous ligation of the retrocoronal venous plexus, deep dorsal vein, and cavernosal veins. The remaining 20 men formed the control group, treated with only a penile implant. Follow-up ranged from 1.1 to 10.0 years, with an average of 6.7 ± 1.5 years. Although preoperative glanular dimension did not differ significantly between the two groups, significant respective difference at one day and one year postoperatively was found in the glanular circumference (128.8 ± 6.8 mm versus 115.3 ± 7.2 mm and 130.6 ± 7.2 mm versus 100.5 ± 7.3 mm; both ), radius (38.8 ± 2.7 mm versus 37.1 ± 2.8 mm and 41.5 ± 2.6 mm versus 33.8 ± 2.9 mm; latter ), and satisfaction rate (91.7% versus 53.3%, ) as well. Based on our results, selective venous ligation appears to enhance the glans penis dimension in implant patients. Geng-Long Hsu, James W. Hill, Cheng-Hsing Hsieh, Shih-Ping Liu, and Chih-Yuan Hsu Copyright © 2014 Geng-Long Hsu et al. All rights reserved. Fibrinogen Alpha Chain Precursor and Apolipoprotein A-I in Urine as Biomarkers for Noninvasive Diagnosis of Calcium Oxalate Nephrolithiasis: A Proteomics Study Wed, 23 Jul 2014 10:45:14 +0000 Calcium oxalate nephrolithiasis is the most common urological disease, but noninvasive and convenient methods of diagnosis are rarely available. Objective. The present study aimed to identify potential urine biomarkers for noninvasive diagnosis of CaOx nephrolithiasis. Methodology. Urine samples from 72 patients with CaOx nephrolithiasis and 30 healthy controls were collected and proteomics analysis was performed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometer (MALDI-TOF-MS). Results. Thirteen proteins/peptides displayed statistically significant differences. The peptides of m/z 1207.23 and 2773.86 were selected by the genetic algorithm (GA) to build a possible diagnostic model. The area under the curve of m/z 1207.23 and 2773.86 was 0.936 and 0.987, respectively. The diagnostic model in distinguishing patients and healthy subjects showed 100% sensitivity and specificity. The peak at m/z 2773.86 was identified as fibrinogen alpha chain (FGA) with the sequence G.EGDFLAEGGGVR.G, and the peak at m/z 2773.86 was identified as apolipoprotein A-I (apoA-I) with the sequence L.PVLESFKVSFLSALEEYTKKLNTQ. Conclusion. The study results strongly suggested that urinary FGA and apoA-I are highly sensitive and specific biomarkers for noninvasive diagnosis of CaOx nephrolithiasis. Wei Zhu, Min Liu, Guang-Chun Wang, Bo Peng, Yang Yan, Jian-Ping Che, Qing-Wei Ma, Xu-Dong Yao, and Jun-Hua Zheng Copyright © 2014 Wei Zhu et al. All rights reserved. Functional MRI in Prostate Cancer Detection Wed, 23 Jul 2014 10:41:11 +0000 Multiparametric magnetic resonance imaging (MP-MRI) has emerged as a promising method for the detection of prostate cancer. The functional MRI components of the MP-MRI consist of the diffusion weighted MRI, dynamic contrast enhanced MRI, and magnetic resonance spectroscopic imaging. The purpose of this paper is to review the existing literature about the use of functional MRI in prostate cancer detection. Sandeep Sankineni, Murat Osman, and Peter L. Choyke Copyright © 2014 Sandeep Sankineni et al. All rights reserved. Treatment of Bilateral Varicocele and Other Scrotal Comorbidities Using a Single Scrotal Access: Our Experience on 34 Patients Wed, 23 Jul 2014 00:00:00 +0000 Introduction. Varicocele is the main cause of infertility in male and the most correctable cause of it too. In this study, we present our experience on 34 patients affected by bilateral varicocele and other scrotal comorbidities treated underwent surgery with a scrotal access. Materials and Methods. 34 patients were enrolled with clinical palpable and infraclinical (ultrasonic doppler scanning) bilateral varicocele and other comorbidities like right hydrocele, left hydrocele, bilateral hydrocele, and epididymal cyst. They all underwent scrotal bilateral varicocelectomy under local anesthesia. Results and Discussion. At 6 months, no other complications were reported. No case of testicular atrophy was observed. None had recurrence of varicocele. All scrotal comorbidities were treated as well. Conclusion. Scrotal access with local anesthesia is a safe and useful technique to treat patients with bilateral varicocele and other scrotal comorbidities. F. Iacono, A. Ruffo, D. Prezioso, G. Romeo, E. Illiano, G. Di Lauro, L. Romis, and S. Sansalone Copyright © 2014 F. Iacono et al. All rights reserved. Alga Ecklonia bicyclis, Tribulus terrestris, and Glucosamine Oligosaccharide Improve Erectile Function, Sexual Quality of Life, and Ejaculation Function in Patients with Moderate Mild-Moderate Erectile Dysfunction: A Prospective, Randomized, Placebo-Controlled, Single-Blinded Study Sun, 20 Jul 2014 07:21:46 +0000 We aimed to evaluate the efficacy of oral therapy with alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide (Tradamix TX1000) in patients with erectile dysfunction (ED) at 3 months of follow-up. From January 2013 to September 2013, 177 patients diagnosed with mild-moderate ED (IIEF-EF < 26) were enrolled in this multicenter, single-blinded, placebo-controlled study and randomized in Group A (Tradamix, ) and Group B (placebo, ). Penile color Doppler ultrasound measures, IIEF-15 questionnaire, male sexual health questionnaire-ejaculation disorder (MSHQ-EjD), and sexual quality of life (SQoL-M) were collected. We observed significant changes of the IIEF-15 in Group A (mean difference: 11.54; ) at 3 months versus Group B (). PSV (), IIEF-intercourse satisfaction (), IIEF-orgasmic function (mean ), IIEF-sexual desire (), IIEF-overall satisfaction (), MSHQ-EjD (mean difference: 1.21; ), and SQoL-M (mean difference: 10.2; ) were significantly changed in Group A versus baseline and Group B. Patients with moderate arterial dysfunction showed significant increase of PSV (), IIEF-EF (), MSHQ-EjD (), and SQoL-M () in Group A. Therapy with Tradamix improves erectile and ejaculation function and sexual quality of life in patients with mild-moderate ED and in particular for those with moderate arterial dysfunction. Salvatore Sansalone, Rosario Leonardi, Gabriele Antonini, Antonio Vitarelli, Giuseppe Vespasiani, Dragoslav Basic, Giuseppe Morgia, Sebastiano Cimino, and Giorgio Ivan Russo Copyright © 2014 Salvatore Sansalone et al. All rights reserved. Acute In Vivo Response to an Alternative Implant for Urogynecology Thu, 17 Jul 2014 14:54:32 +0000 Purpose. To investigate in vivo the acute host response to an alternative implant designed for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). Methods. A biodegradable scaffold was produced from poly-L-lactic acid (PLA) using the electrospinning technique. Human and rat adipose-derived stem cells (ADSCs) were isolated and characterized by fluorescence-activated cell sorting and differentiation assays. PLA scaffolds were seeded and cultured for 2 weeks with human or rat ADSCs. Scaffolds with and without human or rat ADSCs were implanted subcutaneously on the abdominal wall of rats. After 3 and 7 days, 6 animals from each group were sacrificed. Sections from each sample were analyzed by Haematoxylin and Eosin staining, Sirius red staining, and immunohistochemistry for CD68, PECAM-1, and collagen I and III. Results. Animals responded to the scaffolds with an acute macrophage response. After 7 days of implantation, there was extensive host cell penetration, new blood vessel formation, and new collagen deposition throughout the full thickness of the samples without obvious differences between cell-containing and cell-free scaffolds. Conclusions. The acute in vivo response to an alternative implant (both with and without cells) for the treatment of SUI and POP showed good acute integration into the host tissues. Sabiniano Roman Regueros, Maarten Albersen, Stefano Manodoro, Silvia Zia, Nadir I. Osman, Anthony J. Bullock, Christopher R. Chapple, Jan Deprest, and Sheila MacNeil Copyright © 2014 Sabiniano Roman Regueros et al. All rights reserved. Multiparametric MRI in Biopsy Guidance for Prostate Cancer: Fusion-Guided Sun, 13 Jul 2014 07:06:32 +0000 Prostate cancer (PCa) is the most common solid-organ malignancy among American men and the second most deadly. Current guidelines recommend a 12-core systematic biopsy following the finding of an elevated serum prostate-specific antigen (PSA). However, this strategy fails to detect an unacceptably high percentage of clinically significant cancers, leading researchers to develop new, innovative methods to improve the effectiveness of prostate biopsies. Multiparametric-MRI (MP-MRI) has emerged as a promising instrument in identifying suspicious regions within the prostate that require special attention on subsequent biopsy. Fusion platforms, which incorporate the MP-MRI into the biopsy itself and provide active targets within real-time imaging, have shown encouraging results in improving the detection rate of significant cancer. Broader applications of this technology, including MRI-guided focal therapy for prostate cancer, are in early phase trials. Jason T. Rothwax, Arvin K. George, Bradford J. Wood, and Peter A. Pinto Copyright © 2014 Jason T. Rothwax et al. All rights reserved. Stem Cell Based Gene Therapy in Prostate Cancer Thu, 10 Jul 2014 11:25:18 +0000 Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations. Jae Heon Kim, Hong Jun Lee, and Yun Seob Song Copyright © 2014 Jae Heon Kim et al. All rights reserved. Immunocontraceptives: New Approaches to Fertility Control Thu, 10 Jul 2014 06:27:29 +0000 The rapidly increasing global population has bowed the attention of family planning and associated reproductive health programmes in the direction of providing a safe and reliable method which can be used to limit family size. The world population is estimated to exceed a phenomenal 10 billion by the year 2050 A.D., thus presenting a real jeopardy of overpopulation with severe implications for the future. Despite the availability of contraceptive methods, there are over one million elective abortions globally each year due to unintended pregnancies, having devastating impact on reproductive health of women worldwide. This highlights the need for the development of newer and improved contraceptive methods. A novel contraceptive approach that is gaining substantial attention is “immunocontraception” targeting gamete production, gamete outcome, or gamete function. Amongst these, use of sperm antigens (gamete function) seems to be an exciting and feasible approach. However, the variability of immune response and time lag to attain titer among vaccinated individuals after active immunization has highlighted the potential relevance of preformed antibodies in this league. This review is an attempt to analyze the current status and progress of immunocontraceptive approaches with respect to their establishment as a future fertility control agent. Kiranjeet Kaur and Vijay Prabha Copyright © 2014 Kiranjeet Kaur and Vijay Prabha. All rights reserved. A Comparative Performance Analysis of Total PSA, Percentage Free PSA, PSA Velocity, and PSA Density versus the Detection of Primary Circulating Prostate Cells in Predicting Initial Prostate Biopsy Findings in Chilean Men Tue, 01 Jul 2014 00:00:00 +0000 Introduction. PSA parameters have been used in an attempt to improve the diagnostic yield of prostate screening tests; the detection of primary malignant circulating prostate cells (CPCs) may improve the diagnostic yield of screening and therefore avoid unnecessary biopsies. Patients and Methods. Prospective study of all men undergoing initial prostate biopsy due to an elevated total serum PSA. Free percent PSA, PSA velocity, and PSA density were determined. Primary CPCs were detected using standard immunocytochemistry. A positive test for CPCs was defined as one cell PSA (+) P504S (+) in an 8 ml blood sample. Positive predictive and negative predictive values, specificity, and sensitivity were calculated for each test as well as the number of biopsies avoided and cancers missed. Results. 303 men participated in the study of whom 113/303 (37.3%) men had prostate cancer. Of the three PSA based parameters, free percent PSA was superior, sensitivity 70.8%, and specificity 67.4%. Primary CPCs detection had a sensitivity of 88.5% and a specificity of 88.4% avoiding 181 (59.7%) biopsies, detecting 93/95 (98%) of clinically significant cancers, and missing 13 (11.5%) low grade, small volume tumors. Conclusions. The use of primary CPCs as a sequential test could decrease the number of initial prostate biopsies missing those cancers which are treated by active observation. Nigel P. Murray, Eduardo Reyes, Nelson Orellana, Cynthia Fuentealba, and Ricardo Dueñas Copyright © 2014 Nigel P. Murray et al. All rights reserved. Enhanced Efficacy of Bleomycin in Bladder Cancer Cells by Photochemical Internalization Mon, 30 Jun 2014 06:56:31 +0000 Bleomycin is a cytotoxic chemotherapeutic agent widely used in cancer treatment. However, its efficacy in different cancers is low, possibly due to limited cellular internalization. In this study, a novel approach known as photochemical internalization (PCI) was explored to enhance bleomycin delivery in bladder cancer cells (human T24 and rat AY-27), as bladder cancer is a potential indication for use of PCI with bleomycin. The PCI technique was mediated by the amphiphilic photosensitizer disulfonated tetraphenyl chlorin (TPCS2a) and blue light (435 nm). Two additional strategies were explored to further enhance the cytotoxicity of bleomycin; a novel peptide drug ATX-101 which is known to impair DNA damage responses, and the protease inhibitor E-64 which may reduce bleomycin degradation by inhibition of bleomycin hydrolase. Our results demonstrate that the PCI technique enhances the bleomycin effect under appropriate conditions, and importantly we show that PCI-bleomycin treatment leads to increased levels of DNA damage supporting that the observed effect is due to increased bleomycin uptake. Impairing the DNA damage responses by ATX-101 further enhances the efficacy of the PCI-bleomycin treatment, while inhibiting the bleomycin hydrolase does not. Yan Baglo, Lars Hagen, Anders Høgset, Finn Drabløs, Marit Otterlei, and Odrun A. Gederaas Copyright © 2014 Yan Baglo et al. All rights reserved. Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-β and IGF Signaling Wed, 25 Jun 2014 11:06:39 +0000 This review postulates the role of transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF-I/IGF-II) signaling in stromal cells during prostate carcinogenesis and progression. It is known that stromal cells have a reciprocal relationship to the adjacent epithelial cells in the maintenance of structural and functional integrity of the prostate. An interaction between TGF-β and IGF signaling occupies a central part in this stromal-epithelial interaction. An increase in TGF-β and IGF signaling will set off the imbalance of this relationship and will lead to cancer development. A continuous input from TGF-β and IGF in the tumor microenvironment will result in cancer progression. Understanding of these events can help prevention, diagnosis, and therapy of prostate cancer. Chung Lee, Zhenyu Jia, Farah Rahmatpanah, Qiang Zhang, Xiaolin Zi, Michael McClelland, and Dan Mercola Copyright © 2014 Chung Lee et al. All rights reserved. Clinical Significance of Serum Soluble T Cell Regulatory Molecules in Clear Cell Renal Cell Carcinoma Wed, 25 Jun 2014 10:55:04 +0000 To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls (). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage (), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels (). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage (), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other (, ). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC. Akinori Masuda, Kyoko Arai, Daisaku Nishihara, Tomoya Mizuno, Hideo Yuki, Tsunehito Kambara, Hironori Betsunoh, Hideyuki Abe, Masahiro Yashi, Yoshitatsu Fukabori, Ken-Ichiro Yoshida, and Takao Kamai Copyright © 2014 Akinori Masuda et al. All rights reserved. Extremely Low Frequency Magnetic Fields Induce Spermatogenic Germ Cell Apoptosis: Possible Mechanism Sun, 15 Jun 2014 08:15:48 +0000 The energy generated by an extremely low frequency electromagnetic field (ELF-EMF) is too weak to directly induce genotoxicity. However, it is reported that an extremely low frequency magnetic field (ELF-MF) is related to DNA strand breakage and apoptosis. The testes that conduct spermatogenesis through a dynamic cellular process involving meiosis and mitosis seem vulnerable to external stress such as heat, MF exposure, and chemical or physical agents. Nevertheless the results regarding adverse effects of ELF-EMF on human or animal reproductive functions are inconclusive. According to the guideline of the International Commission on Non-Ionizing Radiation Protection (ICNIRP; 2010) for limiting exposure to time-varying MF (1 Hz to 100 kHz), overall conclusion of epidemiologic studies has not consistently shown an association between human adverse reproductive outcomes and maternal or paternal exposure to low frequency fields. In animal studies there is no compelling evidence of causal relationship between prenatal development and ELF-MF exposure. However there is increasing evidence that EL-EMF exposure is involved with germ cell apoptosis in testes. Biophysical mechanism by which ELF-MF induces germ cell apoptosis has not been established. This review proposes the possible mechanism of germ cell apoptosis in testes induced by ELF-MF. Sang-Kon Lee, Sungman Park, Yoon-Myoung Gimm, and Yoon-Won Kim Copyright © 2014 Sang-Kon Lee et al. All rights reserved. Standardization of Multiparametric Prostate MR Imaging Using PI-RADS Mon, 09 Jun 2014 11:44:07 +0000 The purpose of this paper is to introduce and describe the Prostate Imaging and Reporting Archiving Data System (PI-RADS). For every single parameter the PI-RADS scoring system will be explained and magnetic resonance imaging (MRI) examples will be given. In the end two patient cases are presented to explain the overall interpretation score in multiparametric imaging. Joyce G. R. Bomers and Jelle O. Barentsz Copyright © 2014 Joyce G. R. Bomers and Jelle O. Barentsz. All rights reserved. Recent Advances in the Biology of the Urothelium and Applications for Urinary Bladder Dysfunction Mon, 09 Jun 2014 10:56:20 +0000 Rok Romih, Michael Winder, and Gilho Lee Copyright © 2014 Rok Romih et al. All rights reserved. Inhibition of Nitric Oxide Synthase Prevents Muscarinic and Purinergic Functional Changes and Development of Cyclophosphamide-Induced Cystitis in the Rat Sun, 01 Jun 2014 12:35:15 +0000 Nitric oxide (NO) has pivotal roles in cyclophosphamide- (CYP-) induced cystitis during which mucosal nitric oxide synthase (NOS) and muscarinic M5 receptor expressions are upregulated. In cystitis, urothelial muscarinic NO-linked effects hamper contractility. Therefore we wondered if a blockade of this axis also affects the induction of cystitis in the rat. Rats were pretreated with saline, the muscarinic receptor antagonist 4-DAMP (1 mg/kg ip), or the NOS inhibitor L-NAME (30 mg/kg ip) for five days. 60 h before the experiments the rats were treated with saline or CYP. Methacholine-, ATP-, and adenosine-evoked responses were smaller in preparations from CYP-treated rats than from saline-treated ones. Pretreatment with 4-DAMP did not change this relation, while pretreatment with L-NAME normalized the responses in the CYP-treated animals. The functional results were strengthened by the morphological observations; 4-DAMP pretreatment did not affect the parameters studied, namely, expression of muscarinic M5 receptors, P1A1 purinoceptors, mast cell distribution, or bladder wall enlargement. However, pretreatment with L-NAME attenuated the differences. Thus, the current study provides new insights into the complex mechanisms behind CYP-induced cystitis. The NO effects coupled to urothelial muscarinic receptors have a minor role in the development of cystitis. Inhibition of NOS may prevent the progression of cystitis. Patrik Aronsson, Renata Vesela, Martin Johnsson, Yasin Tayem, Vladimir Wsol, Michael Winder, and Gunnar Tobin Copyright © 2014 Patrik Aronsson et al. All rights reserved. Pathological Feature and Immunoprofile of Cystitis Glandularis Accompanied with Upper Urinary Tract Obstruction Thu, 29 May 2014 16:14:23 +0000 Objective. To explore the pathological feature and immunoprofile of immunoprofile accompanied with upper urinary tract obstruction and the immunoprofile in various types of glandular cystitis. Methods. Pathological sections from 31 cases of cystitis glandularis with upper urinary tract obstruction and 34 cases of cystitis glandularis without upper urinary tract obstruction were observed as pathological feature on microscopy. Meanwhile, an immunohistochemical analysis was employed to determine the expression of p53, Ki67, p21, MMP-9, MUC1, MUC2, and COX-2. Results. In the two groups, main pathological type was transitional epithelial, followed by intestinal epithelial; other types were a few, and the difference between the two groups was not significant. All immunohistochemical expressions of p53, Ki67, p21, MMP-9, MUC1, MUC2, and COX-2 were positive in varying degrees, and there was no significant difference between the groups. Transitional epithelial type was compared with mixed type; the difference of COX-2 was significant, . The differences of immunohistochemical expression among other different pathologic types were not significant. Conclusions. It is suggested that glandular cystitis accompanied with upper urinary tract obstruction shares the same pathological feature and immunoprofile as that without upper urinary tract obstruction. No significant differences of immunohistochemical expression in tissue are in cystitis glandularis with different pathological types. Aihua Li, Jun Zhou, Honghai Lu, Xiaoming Zuo, Sikuan Liu, Feng Zhang, Weiwu Li, Wei Fang, and Binghui Zhang Copyright © 2014 Aihua Li et al. All rights reserved. Prostate Cancer and Bone: The Elective Affinities Wed, 28 May 2014 00:00:00 +0000 The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients. Nadia Rucci and Adriano Angelucci Copyright © 2014 Nadia Rucci and Adriano Angelucci. All rights reserved. ATP during Early Bladder Stretch Is Important for Urgency in Detrusor Overactivity Patients Tue, 27 May 2014 11:04:11 +0000 ATP is an important mediator of urgency in women with detrusor overactivity (DO). In order to understand how different degrees of bladder stretch elicited ATP release in DO patients compared with controls, sequential aliquots were collected during cystometry and ATP release was measured at each degree of bladder filling, in female patients with DO and controls. In both DO and control groups, ATP release was induced during bladder filling, suggesting that stretch stimulated further ATP release. However, the luminal ATP concentrations were already high at early filling stage (200 mL), which was even greater than those at the later filling stages (400 mL and maximum cystometric capacity, MCC), indicating that a substantial ATP release has been induced during early filling (200 mL) in both DO and controls. In DO, ATP release at 200 mL was significantly higher in those with low first desire to void (FDV) (≤200 mL) than in those with higher FDV (>200 mL); this may suggest that ATP release at early stretch may play an important role in urgency (early sensation) in DO. ATP concentrations remained unchanged after voiding, suggesting that voiding did not further induce ATP release into intraluminal fluid. Y. Cheng, K. J. Mansfield, W. Allen, R. Chess-Williams, E. Burcher, and K. H. Moore Copyright © 2014 Y. Cheng et al. All rights reserved. Multiparametric MRI for Recurrent Prostate Cancer Post Radical Prostatectomy and Postradiation Therapy Sun, 25 May 2014 09:17:27 +0000 The clinical suspicion of local recurrence of prostate cancer (PCa) after radical prostatectomy (RP) and after radiation therapy (RT) is based on the onset of biochemical failure. The aim of this paper was to review the current role of multiparametric-MRI (mp-MRI) in the detection of locoregional recurrence. A systematic literature search using the Medline and Cochrane Library databases was performed from January 1995 up to November 2013. Bibliographies of retrieved and review articles were also examined. Only those articles reporting complete data with clinical relevance for the present review were selected. This review article is divided into two major parts: the first one considers the role of mp-MRI in the detection of PCa local recurrence after RP; the second part provides an insight about the impact of mp-MRI in the depiction of locoregional recurrence after RT (interstitial or external beam). Published data indicate an emerging role for mp-MRI in the detection and localization of locally recurrent PCa both after RP and RT which represents an information of paramount importance to perform focal salvage treatments. Flavio Barchetti and Valeria Panebianco Copyright © 2014 Flavio Barchetti and Valeria Panebianco. All rights reserved. Exploring the miRNA-mRNA Regulatory Network in Clear Cell Renal Cell Carcinomas by Next-Generation Sequencing Expression Profiles Thu, 22 May 2014 16:11:29 +0000 Altered microRNA (miRNA) expression is a hallmark of many cancer types. The combined analysis of miRNA and messenger RNA (mRNA) expression profiles is crucial to identifying links between deregulated miRNAs and oncogenic pathways. Therefore, we investigated the small non-coding (snc) transcriptomes of nine clear cell renal cell carcinomas (ccRCCs) and adjacent normal tissues for alterations in miRNA expression using a publicly available small RNA-Sequencing (sRNA-Seq) raw-dataset. We constructed a network of deregulated miRNAs and a set of differentially expressed genes publicly available from an independent study to in silico determine miRNAs that contribute to clear cell renal cell carcinogenesis. From a total of 1,672 sncRNAs, 61 were differentially expressed across all ccRCC tissue samples. Several with known implications in ccRCC development, like the upregulated miR-21-5p, miR-142-5p, as well as the downregulated miR-106a-5p, miR-135a-5p, or miR-206. Additionally, novel promising candidates like miR-3065, which i.a. targets NRP2 and FLT1, were detected in this study. Interaction network analysis revealed pivotal roles for miR-106a-5p, whose loss might contribute to the upregulation of 49 target mRNAs, miR-135a-5p (32 targets), miR-206 (28 targets), miR-363-3p (22 targets), and miR-216b (13 targets). Among these targets are the angiogenesis, metastasis, and motility promoting oncogenes c-MET, VEGFA, NRP2, and FLT1, the latter two coding for VEGFA receptors. Sören Müller and Katharina Nowak Copyright © 2014 Sören Müller and Katharina Nowak. All rights reserved. CD57 Expression in Incidental, Clinically Manifest, and Metastatic Carcinoma of the Prostate Thu, 22 May 2014 14:17:35 +0000 Objectives. CD57 is normally found on NK-cells, but little is known about its expression in prostatic tissue. Methods. We investigated CD57 expression by immunohistochemistry using tissue microarrays containing 3262 prostate cancers (PCa), lymph node metastases, and benign prostatic tissue. The results were compared with clinical and pathological parameters. Results. Overall, 87% of PCa showed a moderate or strong expression of CD57. There was no significant difference to corresponding benign prostatic tissue. CD57 was increasingly lost from incidental over clinically manifest cancers to metastases. It correlated significantly with Gleason grade and pT-category, but not with PSA tissue expression. Loss of CD57 expression was an independent risk factor for PSA recurrence after prostatectomy in a multivariate Cox regression analysis. In standard sections, CD57 expression was heterogeneous, especially in large, high-grade PCa. Conclusions. There is a peculiar expression of CD57 in PCa and benign prostatic tissue. CD57 loss is associated with tumor dedifferentiation and tumor size. However, the use of this marker for prognostic purposes is hampered by its heterogeneous expression. Holger Wangerin, Glen Kristiansen, Thorsten Schlomm, Carsten Stephan, Sven Gunia, Annette Zimpfer, Wilko Weichert, Guido Sauter, and Andreas Erbersdobler Copyright © 2014 Holger Wangerin et al. All rights reserved. Sunitinib Combined with Angiotensin-2 Type-1 Receptor Antagonists Induces More Necrosis: A Murine Xenograft Model of Renal Cell Carcinoma Thu, 22 May 2014 11:50:57 +0000 Background. Angiotensin-2 type-1 receptor antagonists not are only antihypertensive drugs but also can inhibit VEGF production. We hypothesised that adding telmisartan to sunitinib could potentiate the antiangiogenic effects. Material and Methods. 786-O cell lines were injected in nude mice. After tumor development, mice were divided into 4 groups: the first was the control group (DMSO), the second group was treated with sunitinib alone, the third group was treated with telmisartan alone, and the fourth group was treated with the combination. Drugs were orally administered every day for four weeks. Animals were sacrificed after treatment. Blood and tumor tissues were collected for analysis by immunohistochemistry, Western Blot, and ELISA methods. Results. All animals developed a ccRCC and ten in each group were treated. Using a kinetic model, tumors tended to grow slower in the combination group compared to others (). Compared to sunitinib alone, the addition of telmisartan significantly increased tissue necrosis (). Central microvascular density decreased () as well as circulating VEGF (). There was no significant variation in proliferation or apoptosis markers. Conclusion. The combination of sunitinib and telmisartan revealed an enhancement of the blockage of the VEGF pathway on renal tumor resulting in a decrease in neoangiogenesis and an increase in necrosis. Grégory Verhoest, Thibault Dolley-Hitze, Florence Jouan, Marc-Antoine Belaud-Rotureau, Emmanuel Oger, Audrey Lavenu, Karim Bensalah, Yannick Arlot-Bonnemains, Nicolas Collet, Nathalie Rioux-Leclercq, and Cécile Vigneau Copyright © 2014 Grégory Verhoest et al. All rights reserved. Epigenetic Alterations of Chromosome 3 Revealed by NotI-Microarrays in Clear Cell Renal Cell Carcinoma Thu, 22 May 2014 10:45:12 +0000 This study aimed to clarify epigenetic and genetic alterations that occur during renal carcinogenesis. The original method includes chromosome 3 specific NotI-microarrays containing 180 NotI-clones associated with 188 genes for hybridization with 23 paired normal/tumor DNA samples of primary clear cell renal cell carcinomas (ccRCC). Twenty-two genes showed methylation and/or deletion in 17–57% of tumors. These genes include tumor suppressors or candidates (VHL, CTDSPL, LRRC3B, ALDH1L1, and EPHB1) and genes that were not previously considered as cancer-associated (e.g., LRRN1, GORASP1, FGD5, and PLCL2). Bisulfite sequencing analysis confirmed methylation as a frequent event in ccRCC. A set of six markers (NKIRAS1/RPL15, LRRN1, LRRC3B, CTDSPL, GORASP1/TTC21A, and VHL) was suggested for ccRCC detection in renal biopsies. The mRNA level decrease was shown for 6 NotI-associated genes in ccRCC using quantitative PCR: LRRN1, GORASP1, FOXP1, FGD5, PLCL2, and ALDH1L1. The majority of examined genes showed distinct expression profiles in ccRCC and papillary RCC. The strongest extent and frequency of downregulation were shown for ALDH1L1 gene both in ccRCC and papillary RCC. Moreover, the extent of ALDH1L1 mRNA level decrease was more pronounced in both histological types of RCC stage III compared with stages I and II (). The same was observed for FGD5 gene in ccRCC (). Alexey A. Dmitriev, Evgeniya E. Rudenko, Anna V. Kudryavtseva, George S. Krasnov, Vasily V. Gordiyuk, Nataliya V. Melnikova, Eduard O. Stakhovsky, Oleksii A. Kononenko, Larissa S. Pavlova, Tatiana T. Kondratieva, Boris Y. Alekseev, Eleonora A. Braga, Vera N. Senchenko, and Vladimir I. Kashuba Copyright © 2014 Alexey A. Dmitriev et al. All rights reserved. Multiple Determinations of Sperm DNA Fragmentation Show That Varicocelectomy Is Not Indicated for Infertile Patients with Subclinical Varicocele Tue, 20 May 2014 11:56:29 +0000 Varicocele is one of the most common causes of low semen quality, which is reflected in high percentages of sperm cells with fragmented DNA. While varicocelectomy is usually performed to ameliorate a patient’s fertility, its impact on sperm DNA integrity in the case of subclinical varicocele is poorly documented. In this study, multiple DNA fragmentation analyses (TUNEL, SCD, and SCSA) were performed on semen samples from sixty infertile patients with varicocele (15 clinical varicoceles, 19 clinical varicoceles after surgical treatment, 16 subclinical varicoceles, and 10 subclinical varicoceles after surgical treatment). TUNEL, SCD, and SCSA assays all showed substantial sperm DNA fragmentation levels that were comparable between subclinical and clinical varicocele patients. Importantly, varicocelectomy did improve sperm quality in patients with clinical varicocele; however, this was not the case in patients with subclinical varicocele. In summary, although infertile patients with clinical and subclinical varicocele have similar sperm DNA quality, varicocelectomy should only be advised for patients with clinical varicocele. Agustín García-Peiró, Jordi Ribas-Maynou, María Oliver-Bonet, Joaquima Navarro, Miguel A. Checa, Alexandros Nikolaou, María J. Amengual, Carlos Abad, and Jordi Benet Copyright © 2014 Agustín García-Peiró et al. All rights reserved. The Role of Histone Ubiquitination during Spermatogenesis Mon, 19 May 2014 00:00:00 +0000 Protein ubiquitin-proteasome (ubiquitin-proteasome) system is the major mechanism responsible for protein degradation in eukaryotic cell. During spermatogenesis, the replacement of histone by protamine is vital for normal sperm formation, which is involved in ubiquitination enzymes expressed in testis. Recently, histone ubiquitin ligases have been shown to play critical roles in several aspects of spermatogenesis, such as meiotic sex chromosome inactivation (MSCI), DNA damage response, and spermiogenesis. In this review, we highlight recent progress in the discovery of several histone ubiquitin ligases and elaborate mechanisms of how these enzymes are involved in these processes through knockout mouse model. Using Huwe1, UBR2, and RNF8 as examples, we emphasized the diverse functions for each enzyme and the broad involvement of these enzymes in every stage, from spermatogonia differentiation and meiotic division to spermiogenesis; thus histone ubiquitin ligases represent a class of enzymes, which play important roles in spermatogenesis through targeting histone for ubiquitination and therefore are involved in transcription regulation, epigenetic modification, and other processes essential for normal gametes formation. Kai Sheng, Xiaotong Liang, Sizhou Huang, and Wenming Xu Copyright © 2014 Kai Sheng et al. All rights reserved. Luminal DMSO: Effects on Detrusor and Urothelial/Lamina Propria Function Sun, 18 May 2014 12:12:08 +0000 DMSO is used as a treatment for interstitial cystitis and this study examined the effects of luminal DMSO treatment on bladder function and histology. Porcine bladder was incubated without (controls) or with DMSO (50%) applied to the luminal surface and the release of ATP, acetylcholine, and LDH assessed during incubation and in tissues strips after DMSO incubation. Luminally applied DMSO caused ATP, Ach, and LDH release from the urothelial surface during treatment, with loss of urothelial layers also evident histologically. In strips of urothelium/lamina propria from DMSO pretreated bladders the release of both ATP and Ach was depressed, while contractile responses to carbachol were enhanced. Detrusor muscle contractile responses to carbachol were not affected by DMSO pretreatment, but neurogenic responses to electrical field stimulation were enhanced. The presence of an intact urothelium/lamina propria inhibited detrusor contraction to carbachol by 53% and this inhibition was significantly reduced in DMSO pretreated tissues. Detection of LDH in the treatment medium suggests that DMSO permeabilised urothelial membranes causing leakage of cytosolic contents including ATP and Ach rather than enhancing release of these mediators. The increase in contractile response and high levels of ATP are consistent with initial flare up in IC/PBS symptoms after DMSO treatment. Katrina J. Smith, Russ Chess-Williams, and Catherine McDermott Copyright © 2014 Katrina J. Smith et al. All rights reserved. Nonsteroidal Anti-Inflammatory Drugs and Prostatic Diseases Mon, 12 May 2014 06:48:12 +0000 Prostatic diseases are characterized by increased activity of cytokines, growth factors, and cyclooxygenases- (COX-) 1 and 2. Activation of COX-1 and COX-2 results in increased levels of prostaglandins and the induction of angiogenic, antiapoptotic and inflammatory processes. Inhibition of COX enzymes by members of the widely used nonsteroidal anti-inflammatory drug (NSAID) class of drugs decreases prostaglandin production, and exerts a variety of anti-inflammatory, antipyretic, and antinociceptive effects. While numerous in vitro, in vivo, and clinical studies have shown that NSAIDs inhibit the risk and progression of prostatic diseases, the relationship between NSAIDs and such diseases remains controversial. Here we review the literature in this area, critically analyzing the benefits and caveats associated with the use of NSAIDs in the treatment of prostatic diseases. Hitoshi Ishiguro and Takashi Kawahara Copyright © 2014 Hitoshi Ishiguro and Takashi Kawahara. All rights reserved. Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders Thu, 08 May 2014 09:35:27 +0000 Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC), feline interstitial cystitis (FIC), and nonneurogenic idiopathic overactive bladder (OAB). These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology. Susan K. Keay, Lori A. Birder, and Toby C. Chai Copyright © 2014 Susan K. Keay et al. All rights reserved. Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target Thu, 08 May 2014 06:40:58 +0000 Urothelium, in addition to its primary function of barrier, is now understood to act as a complex system of cell communication that exhibits specialized sensory properties in the regulation of physiological or pathological stimuli. Furthermore, it has been hypothesized that bladder inflammation and neoplastic cell growth, the two most representative pathological conditions of the lower urinary tract, may arise from a primary defective urothelial lining. Transient receptor potential vanilloid channel 1 (TRPV1), a receptor widely distributed in lower urinary tract structures and involved in the physiological micturition reflex, was described to have a pathophysiological role in inflammatory conditions and in the genesis and development of urothelial cancer. In our opinion new compounds, such as curcumin, the major component of turmeric Curcuma longa, reported to potentiate the effects of the chemotherapeutic agents used in the management of recurrent urothelial cancer in vitro and also identified as one of several compounds to own the vanillyl structure required to work like a TRPV1 agonist, could be thought as complementary in the clinical management of both the recurrences and the inflammatory effects caused by the endoscopic resection or intravesical chemotherapy administration or could be combined with adjuvant agents to potentiate their antitumoral effect. Francesco Mistretta, Nicolò Maria Buffi, Giovanni Lughezzani, Giuliana Lista, Alessandro Larcher, Nicola Fossati, Alberto Abrate, Paolo Dell’Oglio, Francesco Montorsi, Giorgio Guazzoni, and Massimo Lazzeri Copyright © 2014 Francesco Mistretta et al. All rights reserved. Neovaginal Prolapse in Male-to-Female Transsexuals: An 18-Year-Long Experience Wed, 07 May 2014 13:48:10 +0000 Neovaginal prolapse is a rare and distressing complication after male-to-female sexual reassignment surgery. We retrospectively analysed the prevalence of partial and total neo-vaginal prolapses after sexual reassignment surgery in our institute. During the years, two different techniques have been adopted with the aim of fixing the neovaginal cylinder. In the first, two absorbable sutures are placed at the top of the penoscrotal cylinder and fixed to the Denonvilliers fascia. In the second, two additional sutures are added from the posterior/midpoint of the flap to the prerectal fascia. We enrolled 282 consecutive transsexual patients. 65 (23.04%) out of the 282 were treated with the first technique and the following 217 (76.96%) with the last technique. In the first technique, 1 case (1.53%) of total prolapse and 7 cases (10.76%) of partial prolapse were observed, while in the other 217 patients treated with the second technique only 9 cases of partial prolapse were observed (4.14%) and no cases of total prolapse. All prolapses occurred within 6 months from the procedure. In our experience, the use of 4 stitches and a more proximal positioning of the sutures to fix the penoscrotal apex with the Denonvilliers fascia guarantees a lower risk of prolapse. Stefano Bucci, Giorgio Mazzon, Giovanni Liguori, Renata Napoli, Nicola Pavan, Susanna Bormioli, Giangiacomo Ollandini, Bernardino De Concilio, and Carlo Trombetta Copyright © 2014 Stefano Bucci et al. All rights reserved. Cystitis: From Urothelial Cell Biology to Clinical Applications Wed, 30 Apr 2014 12:44:03 +0000 Cystitis is a urinary bladder disease with many causes and symptoms. The severity of cystitis ranges from mild lower abdominal discomfort to life-threatening haemorrhagic cystitis. The course of disease is often chronic or recurrent. Although cystitis represents huge economical and medical burden throughout the world and in many cases treatments are ineffective, the mechanisms of its origin and development as well as measures for effective treatment are still poorly understood. However, many studies have demonstrated that urothelial dysfunction plays a crucial role. In the present review we first discuss fundamental issues of urothelial cell biology, which is the core for comprehension of cystitis. Then we focus on many forms of cystitis, its current treatments, and advances in its research. Additionally we review haemorrhagic cystitis with one of the leading causative agents being chemotherapeutic drug cyclophosphamide and summarise its management strategies. At the end we describe an excellent and widely used animal model of cyclophosphamide induced cystitis, which gives researches the opportunity to get a better insight into the mechanisms involved and possibility to develop new therapy approaches. Gilho Lee, Rok Romih, and Daša Zupančič Copyright © 2014 Gilho Lee et al. All rights reserved. Significance of Chromosome 9p Status in Renal Cell Carcinoma: A Systematic Review and Quality of the Reported Studies Wed, 30 Apr 2014 08:15:14 +0000 Defining the prognosis of renal cell carcinoma (RCC) using genetic tests is an evolving area. The prognostic significance of 9p status in RCC, although described in the literature, remains underutilised in clinical practice. The study explored the causes of this translational gap. A systematic review on the significance of 9p status in RCC was performed to assess its clinical applicability and impact on clinical decision-making. Medline, Embase, and other electronic searches were made for studies reporting on 9p status in RCC. We collected data on: genetic techniques, pathological parameters, clinical outcomes, and completeness of follow-up assessment. Eleven studies reporting on 1,431 patients using different genetic techniques were included. The most commonly used genetic technique for the assessment of 9p status in RCC was fluorescence in situ hybridization. Combined genomic hybridisation (CGH), microsatellite analysis, karyotyping, and sequencing were other reported techniques. Various thresholds and cut-off values were used for the diagnosis of 9p deletion in different studies. Standardization, interobserver agreement, and consensus on the interpretation of test remained poor. The studies lacked validation and had high risk of bias and poor clinical applicability as assessed by two independent reviewers using a modified quality assessment tool. Further protocol driven studies with standardised methodology including use of appropriate positive and negative controls, assessment of interobserver variations, and evidenced based follow-up protocols are needed to clarify the role of 9p status in predicting oncological outcomes in renal cell cancer. Ismail El-Mokadem, John Fitzpatrick, Bhavan Rai, J. Cunningham, Norman Pratt, Stewart Fleming, and Ghulam Nabi Copyright © 2014 Ismail El-Mokadem et al. All rights reserved. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder Sun, 27 Apr 2014 13:58:18 +0000 Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns. Igor Sterle, Daša Zupančič, and Rok Romih Copyright © 2014 Igor Sterle et al. All rights reserved. Effect of Inflammatory Mediators on ATP Release of Human Urothelial RT4 Cells Tue, 15 Apr 2014 11:29:49 +0000 Inflammation is an important contributor to the aetiology of a number of bladder dysfunctions including interstitial cystitis, painful bladder syndrome, and overactive bladder. The aim of this study was to examine the effects of inflammatory mediators on urothelial ATP release. Human urothelial RT4 cells were exposed to normal buffer or varying concentrations of inflammatory mediators (bradykinin, histamine, and serotonin) in the presence or absence of hypotonic stretch stimuli (1 : 2 dilution of Krebs-Henseleit buffer). Others have demonstrated that bradykinin increased stretch-induced ATP release; however, we observed no change in control or stretch-induced ATP release with bradykinin. Pretreatment of RT4 cells with histamine or serotonin decreased stretch-induced ATP release (, , resp.). Previous studies have demonstrated increased ATP release in response to inflammation utilising whole bladder preparations in contrast to our simple model of cultured urothelial cells. The current study suggests that it is unlikely that there is a direct interaction between the release of inflammatory mediators and increased ATP release, but rather more complex interactions occurring in response to inflammation that lead to increased bladder sensation. Kylie J. Mansfield and Jessica R. Hughes Copyright © 2014 Kylie J. Mansfield and Jessica R. Hughes. All rights reserved. Alterations of the Myovesical Plexus of the Human Overactive Detrusor Tue, 15 Apr 2014 00:00:00 +0000 Objectives. The human bladder shows spontaneous autonomous activity. Detrusor overactivity could be seen as a consequence of exaggerated autonomous activity. Interstitial cells (ICs) play a potential role in coordination of autonomous activity. As it is suggested that changes in ICs coexist with detrusor overactivity (DO), we investigated possible alterations to human bladder ICs. Methods. Biopsies were obtained from 23 patients and were categorized into four groups: genuine stress incontinence (without DO) (), neurogenic disease with DO (), bladder outlet obstruction with DO (), or idiopathic DO (). Specimens were processed to investigate expression of N-cadherin and PGP9.5. N-cadherin expression was semiquantitatively analyzed and correlated to PG9.5 expression and bladder wall morphology. Results. The population of cells expressing N-cadherin is altered in the overactive detrusor, making no difference between the sources of DO. Punctate distribution of morphological changes was found and downregulation of PGP9.5 expression seemed to coexist with upregulation of N-cadherin expression in the detrusor layer. Conclusions. The population of N-cadherin+ cells of the interstitial compartment of the human bladder has the ability to proliferate. As this proliferation seems to coexist with denervation, it could be possible that a highly developed network of interstitial cells replaces the loss of innervation in overactive detrusor. Kamiel A. J. Kuijpers, John P. F. A. Heesakkers, and Jack A. Schalken Copyright © 2014 Kamiel A. J. Kuijpers et al. All rights reserved. Nonkeratinised Squamous Metaplasia of the Urinary Bladder in Children: A Report of Case Experiences Tue, 15 Apr 2014 00:00:00 +0000 Background. Squamous metaplasia refers to the pathological transformation of the urothelium leading to nonkeratinised stratified squamous metaplasia (N-KSM). Objective. To present our experiences in the diagnosis and treatment of N-KSM of the urinary bladder in children. Materials and Methods. In this study, we present our experiences in the diagnosis and treatment of N-KSM of the urinary bladder in children aged from 5 to 17 years. From 2005 to 2013, metaplasia was diagnosed in 119 patients. The reasons behind visiting the hospital were nonspecific intense pain in the abdomen, recurrent urinary tract infections, and urination disorders. The most common symptoms of urinary bladder dysfunction were pollakiuria and difficulties in initiating micturition and retention of urine (reduced detrusor muscle activity). Results. In 20/119 patients (16.8%), metaplasia was incidentally diagnosed during cystoscopy performed for other causes. The changes characteristic for squamous metaplasia were diagnosed—in all these patients, a biopsy was performed. In all 119 patients, a squamous metaplasia was histopathologically diagnosed. Conclusions. Squamous metaplasia of the urinary bladder mucosa occurs in children and adolescents. Symptomatic treatment is administered mainly to improve the patients’ quality of life and disease prognosis. Beata Jurkiewicz and Tomasz Ząbkowski Copyright © 2014 Beata Jurkiewicz and Tomasz Ząbkowski. All rights reserved. P2Y Receptor Modulation of ATP Release in the Urothelium Mon, 14 Apr 2014 17:21:01 +0000 The release of ATP from the urothelium in response to stretch during filling demonstrates the importance of the purinergic system for the physiological functioning of the bladder. This study examined the effect of P2 receptor agonists on ATP release from two urothelial cell lines (RT4 and UROtsa cells). Hypotonic Krebs was used as a stretch stimulus. Incubation of urothelial cells with high concentrations of the P2Y agonist ADP induced ATP release to a level that was 40-fold greater than hypotonic-stimulated ATP release (P < 0.0011, ADP EC50 1.8 µM). Similarly, an increase in ATP release was also observed with the P2Y agonist, UTP, up to a maximum of 70% of the hypotonic response (EC50 0.62 µM). Selective P2 receptor agonists, αβ-methylene-ATP, ATP-γ-S, and 2-methylthio-ADP had minimal effects on ATP release. ADP-stimulated ATP release was significantly inhibited by suramin (100 µM, P = 0.002). RT4 urothelial cells break down nucleotides (100 µM) including ATP, ADP, and UTP to liberate phosphate. Phosphate liberation was also demonstrated from endogenous nucleotides with approximately 10% of the released ATP broken down during the incubation. These studies demonstrate a role for P2Y receptor activation in stimulation of ATP release and emphasize the complexity of urothelial P2 receptor signalling. Kylie J. Mansfield and Jessica R. Hughes Copyright © 2014 Kylie J. Mansfield and Jessica R. Hughes. All rights reserved. Urinary Angiotensinogen Is Elevated in Patients with Nephrolithiasis Wed, 09 Apr 2014 07:15:46 +0000 Background. Elevated urinary angiotensinogen (UA) was identified as novel prognostic biomarker capable of predicting chronic kidney disease, and in the present study, we will investigate the diagnostic value of UA in the patients of nephrolithiasis. Methods. Urine angiotensinogen levels and α1-microglobulin were measured by enzyme-linked immunosorbent assay (ELISA) in 60 patients presenting with nephrolithiasis and 50 sex- and age-matched healthy volunteers. Estimated glomerular filtration (eGFR) was calculated and, by simple regression analysis, the correlation of UA/α1-microglobulin levels and the decline of eGFR were analyzed as well. Results. Median UA levels was significantly increased in the nephrolithiasis patients compared with normal control (1250.78 439.27 versus 219.34 45.27 pg/mL; ). The mean serum creatinine levels in patients with higher UA levels (1250 pg/mL) was significantly higher than those with lower UA levels (1250 pg/mL) [92.23 18.13 μmol/L versus 70.07 11.17 μmol/L; ]. According to the single variate analysis, UA levels were significantly and positively correlated with urinary α1-microglobulin (; ), while they were significantly and negatively correlated with eGFR (; ). Conclusion. Urinary UA is a novel biomarker for patients with nephrolithiasis, which indicates renal tubular injury. Further study on the molecular pathogenic mechanism of UA and larger scale of clinical trial is required. Wei Sun, Yuan Feng, Xu-Dong Yao, Yun-Fei Xu, Bo Peng, Min Liu, and Jun-Hua Zheng Copyright © 2014 Wei Sun et al. All rights reserved. Kallikreins as Biomarkers for Prostate Cancer Mon, 07 Apr 2014 07:09:08 +0000 The introduction of testing for prostate-specific antigen (PSA), a member of the fifteen-gene family of kallikrein-related peptidases and also known as kallikrein-related peptidase 3 (KLK3), in blood has revolutionized both the detection and management of prostate cancer. Given the similarities between PSA and other KLK gene family members along with limitations of PSA as a biomarker for prostate cancer mainly in reference to diagnostic specificity, the potential roles of other members of this gene family as well as PSA derivatives and isoforms in the management of prostate cancer have been studied extensively. Of these, approaches to measure distinct molecular forms of PSA (free, intact, complexed PSA, and pro-PSA) combined with kallikrein-related peptidase 2 (KLK2), also known as hK2, have been considered holding particular promise in enhancing the diagnosis of prostate cancer. Recently, an integrated approach of applying a panel of four kallikrein markers has been demonstrated to enhance accuracy in predicting the risk of prostate cancer at biopsy. This review presents an overview of kallikreins, starting with the past and current status of PSA, summarizing published data on the evaluations of various KLKs as biomarkers in the diagnosis, prognostication, and monitoring of prostate cancer. Sung Kyu Hong Copyright © 2014 Sung Kyu Hong. All rights reserved. Inflammatory Reaction as Determinant of Foreign Body Reaction Is an Early and Susceptible Event after Mesh Implantation Wed, 26 Mar 2014 00:00:00 +0000 Purpose. To investigate and relate the ultrashort-term and long-term courses of determinants for foreign body reaction as biocompatibility predictors for meshes in an animal model. Materials and Methods. Three different meshes (TVT, UltraPro, and PVDF) were implanted in sheep. Native and plasma coated meshes were placed bilaterally: (a) interaperitoneally, (b) as fascia onlay, and (c) as muscle onlay (fascia sublay). At 5 min, 20 min, 60 min, and 120 min meshes were explanted and histochemically investigated for inflammatory infiltrate, macrophage infiltration, vessel formation, myofibroblast invasion, and connective tissue accumulation. The results were related to long-term values over 24 months. Results. Macrophage invasion reached highest extents with up to 60% in short-term and decreased within 24 months to about 30%. Inflammatory infiltrate increased within the first 2 hours, the reached levels and the different extents and ranking among the investigated meshes remained stable during long-term follow up. For myofibroblasts, connective tissue, and CD31+ cells, no activity was detected during the first 120 min. Conclusion. The local inflammatory reaction is an early and susceptible event after mesh implantation. It cannot be influenced by prior plasma coating and does not depend on the localisation of implantation. Holger Gerullis, Evangelos Georgas, Mihaly Borós, Bernd Klosterhalfen, Christoph Eimer, Christian Arndt, Stephan Otto, Dimitri Barski, Dirk Ysebaert, Albert Ramon, and Thomas Otto Copyright © 2014 Holger Gerullis et al. All rights reserved. Bioenergetics of Mammalian Sperm Capacitation Tue, 25 Mar 2014 13:26:51 +0000 After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods. Alessandra Ferramosca and Vincenzo Zara Copyright © 2014 Alessandra Ferramosca and Vincenzo Zara. All rights reserved. Disturbances of Sperm Maturation and Minipuberty: Is There a Connection? Thu, 13 Mar 2014 00:00:00 +0000 Male reproductive function in the general population raises an increased attention due to reports indicating declining sperm counts, increased occurrence of testicular cancer, cryptorchidism, and hypospadias. It is also hypothesized that prolonged exposure of the developing male, during both fetal and postnatal life, to exogenous estrogens could reduce Sertoli cell number and thus reduce sperm output (and sperm counts) in adult life. Fact is that infertility, which is defined as the inability to conceive after 1 year of unprotected intercourse, has a global prevalence of 9%. A male contributory factor is involved in approximately half of these cases, but most of the causes of reduced semen quality and other disturbances of male reproductive function are unknown. In the most affected men (azoospermic men) 15–20% had a prior history of cryptorchidism. The association between the cryptorchidism and infertility is one of the most studied potential causes of infertility. There are numerous studies that accentuate the importance of minipuberty for future fertility. Is it possible that a normal minipuberty ensures normal fertility despite malpositioned testes? And to move away from cryptorchidism, could impaired minipuberty be responsible for fertility problems in men who were born with both testes in their scrotal sacs? D. Živković and I. Fratrić Copyright © 2014 D. Živković and I. Fratrić. All rights reserved. The Role(s) of Cytokines/Chemokines in Urinary Bladder Inflammation and Dysfunction Wed, 12 Mar 2014 00:00:00 +0000 Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3–7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed. Altered visceral sensations from the urinary bladder (i.e., pain at low or moderate bladder filling) that accompany BPS/IC may be mediated by many factors including changes in the properties of peripheral bladder afferent pathways such that bladder afferent neurons respond in an exaggerated manner to normally innocuous stimuli (allodynia). The goals for this review are to describe chemokine/receptor (CXCL12/CXCR4; CCL2/CCR2) signaling and cytokine/receptor (transforming growth factor (TGF-β)/TGF-β type 1 receptor) signaling that may be valuable LUT targets for pharmacologic therapy to improve urinary bladder function and reduce somatic sensitivity associated with urinary bladder inflammation. Eric J. Gonzalez, Lauren Arms, and Margaret A. Vizzard Copyright © 2014 Eric J. Gonzalez et al. All rights reserved. Microscopic Varicocelectomy Significantly Decreases the Sperm DNA Fragmentation Index in Patients with Infertility Mon, 10 Mar 2014 09:14:02 +0000 Background. Varicocele is associated with high levels of DNA damage in spermatozoa due to oxidative stress and elevated levels of sperm DNA fragmentation, which has been currently proposed to be an essential additional diagnostic test to be recommended for patients with clinical varicocele. The aim of this study was to evaluate the parameters of semen and the DNA fragmentation index (DFI) in patients with varicocele before and after varicocelectomy. Methods. The details of 92 consecutive patients were retrospectively analyzed from January 2010 to December 2012. The sperm samples were evaluated according to the World Health Organization Guidelines. Sperm DNA damage, characterized as DFI, was evaluated by sperm chromatin structure assay using flow cytometry. Results. There was a statistically significant improvement in the semen concentration, the total motile count, the total normal sperm count, and the sperm DNA fragmentation index (DFI; the percentage of sperm with denatured DNA) after varicocelectomy. There was a large decrease in DFI from a preoperative mean of 42.6% to a postoperative mean of 20.5% (). A higher preoperative DFI was associated with a larger decrease in postoperative DFI, and significant negative correlations were observed between the DFI and sperm motility (, ). Conclusion. Our data suggest that varicocelectomy can improve multiple semen parameters and sperm DNA damage in infertile men with varicocele. The patients with preoperative defects in those parameters showed greater improvement postoperatively. Further research in this area is needed to understand the exact mechanisms of DNA damage in infertile men with varicocele. Teoman Cem Kadioglu, Emin Aliyev, and Murad Celtik Copyright © 2014 Teoman Cem Kadioglu et al. All rights reserved. The Dynamic of the Apical Ectoplasmic Specialization between Spermatids and Sertoli Cells: The Case of the Small GTPase Rap1 Thu, 27 Feb 2014 09:01:19 +0000 Despite advances in assisted reproductive technologies, infertility remains a consistent health problem worldwide. Spermiation is the process through which mature spermatids detach from the supporting Sertoli cells and are released into the tubule lumen. Spermiation failure leads to lack of mature spermatozoa and, if not occasional, could result into azoospermia, major cause of male infertility in human population. Spermatids are led through their differentiation into spermatozoa by the apical ectoplasmic specialization (aES), a testis-specific, actin-based anchoring junction restricted to the Sertoli-spermatid interface. The aES helps spermatid movement across the seminiferous epithelium, promotes spermatid positioning, and prevents the release of immature spermatozoa. To accomplish its functions, aES needs to undergo tightly and timely regulated restructuring. Even if components of aES are partly known, the mechanism/s through which aES is regulated remains still elusive. In this review, we propose a model by which the small GTPase Rap1 could regulate aES assembly/remodelling. The characterization of key players in the dynamic of aES, such as Rap1, could open new possibility to develop prognostic, diagnostic, and therapeutic approaches for male patients under treatment for infertility as well as it could lead to the identification of new target for male contraception. Giovanna Berruti and Chiara Paiardi Copyright © 2014 Giovanna Berruti and Chiara Paiardi. All rights reserved. An Update of the Interstitial Cell Compartment in the Normal Human Bladder Thu, 27 Feb 2014 06:34:56 +0000 Aims. Interstitial cells, also called myofibroblasts, most probably play a major role in the pathogenesis of the overactive bladder. However, no specific phenotypic marker has been identified. We investigated whether N-cadherin could play a role as a discriminatory marker for interstitial cells in the human bladder. Methods. Bladder biopsies (n = 16) were collected from macroscopically nonpathological locations during cystectomy which was performed because of bladder cancer. Tissue was analyzed for expression of N-cadherin. N-cadherin+ cells were phenotyped using antibodies against PGP9.5, smoothelin, vimentin, and C-kit. Findings were related to bladder tissue histology and ultrastructure of myofibroblastic cells. Results. N-cadherin+/vimentin+ cells with branched cell bodies were found in the lamina propria and detrusor layer. They were closely associated with neurons and showed no colocalization of PGP9.5 or smoothelin. A second type of N-cadherin+ cells was found at the boundary of detrusor bundles and in the lamina propria. These cells colocalization C-kit. We assumed that N-cadherin+/vimentin+ cells are similar to the ultrastructurally defined myofibroblasts. Conclusions. N-cadherin can play a role as a discriminatory marker for interstitial cells in the human bladder, as the interstitial compartment of the human bladder houses a population of cells from mesenchymal origin, immunopositive for N-cadherin, vimentin, and C-kit. Kamiel A. J. Kuijpers, John P. F. A. Heesakkers, Theo G. M. Hafmans, and Jack A. Schalken Copyright © 2014 Kamiel A. J. Kuijpers et al. All rights reserved. Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells Sun, 19 Jan 2014 00:00:00 +0000 Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by ultracentrifugation from bladder cancer culture conditioned supernatant, labeled with PKH-26, and analyzed on the ImageStreamX with an internal standard added to determine concentration. Exosomes were cocultured with bladder cancer cells and analyzed for internalization. Using the IDEAS software, we determined exosome uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence intensity. Using unlabeled beads of a known concentration and size, we were able to determine concentrations of exosomes isolated from bladder cancer cells. We measured exosome uptake by recipient bladder cancer cells, and we demonstrated that uptake is dose and time dependent. Finally, we found that uptake is active and specific, which can be partially blocked by heparin treatment. The characterization of cellular uptake and internalization by bladder cancer cells may shed light on the role of exosomes on bladder cancer recurrence and progression. Carrie A. Franzen, Patricia E. Simms, Adam F. Van Huis, Kimberly E. Foreman, Paul C. Kuo, and Gopal N. Gupta Copyright © 2014 Carrie A. Franzen et al. All rights reserved. The CFTR M470V, Intron 8 Poly-T, and 8 TG-Repeats Detection in Chinese Males with Congenital Bilateral Absence of the Vas Deferens Wed, 08 Jan 2014 15:59:43 +0000 Purpose. To evaluate the significance of molecular detection of cystic fibrosis transmembrane conductance regulator (CFTR) M470V, intron 8 poly-T, and intron 8 TG-repeats in congenital bilateral absence of the vas deferens (CBAVD). Methods. Eighty-nine male patients with CBAVD and 103 healthy males were included in this study. Polymerase chain reaction was performed to amplify the polymorphic regions using primers from conserved regions. M470V was genotyped using real-time PCR by cycling probe. The exon 9 DNA sequence was determined using an automated sequencer. TG-repeats and poly-T were identified by direct sequencing analysis. Results. The 5T allele distribution was 0.32, 0.66 for 7T, and 0.02 for 9T in CBAVD males, respectively. In contrast, the 5T allele distribution was 0.03, 0.96 for 7T, and 0.01 for 9T in healthy control. Study of the polymorphisms of the upstream of exon 9 revealed a higher frequency of 5T allele in the CBAVD males. All cases with TG13T5 haplotype and TG12T5 homozygous led to CBAVD. The CFTR TG12T5-V470 variant haplotype was associated with CBAVD. Conclusion. The 5T allele of intron 8 of CFTR has clinically significant association with CBAVD. TG13T5 and TG12T5 homozygously led to CBAVD, and TG12T5-V470 may also lead to CBAVD. Qiang Du, Zheng Li, Yongfeng Pan, Xiaoliang Liu, Bochen Pan, and Bin Wu Copyright © 2014 Qiang Du et al. All rights reserved. Cytokeratin 18 Is Not Required for Morphogenesis of Developing Prostates but Contributes to Adult Prostate Regeneration Mon, 30 Dec 2013 12:01:55 +0000 Cytokeratin 18 (CK18) is a key component of keratin-containing intermediate filaments and has long been used as a classic luminal cell marker in prostatic tissue. However, the in vivo function of CK18 in prostate is not known so far. We reported in this study, unexpectedly, that deletion of CK18 in a mouse model did not affect the morphological or the histological structures of adult prostate, as the CK18 knockout prostate displayed a normal glandular ductal structure, branching pattern, and composition of both luminal and basal cells. However, CK18 loss compromised the regenerative tubular branching in dorsolateral prostate after castration and androgen replacement. Therefore, in contrast to its importance as luminal cell marker, CK18 is dispensable for the prostate morphogenesis but contributes to adult prostate regeneration. Chenlu Zhang, Yanjing Guo, Jian Cui, Helen He Zhu, and Wei-Qiang Gao Copyright © 2013 Chenlu Zhang et al. All rights reserved. Contrast Enhanced Ultrasound of the Kidneys: What Is It Capable of? Tue, 24 Dec 2013 16:57:18 +0000 One of the many imaging uses of contrast enhanced ultrasound (CEUS) is studying a wide variety of kidney pathology, due to its ability to detect microvascular blood flow in real time without affecting renal function. CEUS enables dynamic assessment and quantification of microvascularisation up to capillary perfusion. The objective of this paper is to briefly refresh basic knowledge of ultrasound (US) contrast agents’ physical properties, to study technical details of CEUS scanning in the kidneys, and to review the commonest renal indications for CEUS, with imaging examples in comparison to baseline unenhanced US and computed tomography when performed. Safety matters and limitations of CEUS of the kidneys are also discussed. Demosthenes D. Cokkinos, Eleni G. Antypa, Maria Skilakaki, Despoina Kriketou, Ekaterini Tavernaraki, and Ploutarchos N. Piperopoulos Copyright © 2013 Demosthenes D. Cokkinos et al. All rights reserved. Introducing a Method of In Vitro Testing of Different Anchoring Systems Used for Female Incontinence and Prolapse Surgery Sun, 22 Dec 2013 10:54:42 +0000 Aims. To develop a method for in vitro testing to compare different intracorporeal anchoring systems (AS) used, for example, in single-incision slings or vaginal meshes. Intracorporeal fixation needs reliable anchorage systems, which keep the implant in the operative and early postoperative phase in place. Up to now, the impact of the design of current anchor systems and their capability to provide sufficient retention forces is not known. Methods. Four AS (“PelFix”, “Surelift”, “TFS”, and “MiniArc”) were evaluated in an animal model and a ballistic gelatine model with pull-out tests. We performed ANOVA with post hoc Bonferroni. Results were presented as mean values whereby a significance level of <0.05 was considered significant. Results. The four systems showed significantly different pull-out forces. Depending on mesh structure, size, and form of the AS, mechanical strain resulted in deformation with local peak stresses. Under the condition of form stability, relative differences of pull-out forces did not change in different tissues. Conclusions. Reliable testing of different AS in their ability to keep mesh implants in place can be done in animal models and in especially designed ballistic gelatine. These methods of testing will help to modify AS in novel pelvic floor implants. Ralf Anding, Ruth Tabaza, Manfred Staat, Eva Trenz, Philipp Lohmann, Uwe Klinge, and Ruth Kirschner-Hermanns Copyright © 2013 Ralf Anding et al. All rights reserved. Hemizona Assay and Sperm Penetration Assay in the Prediction of IVF Outcome: A Systematic Review Mon, 21 Oct 2013 14:47:04 +0000 The limited predictive value of semen analysis in achieving natural conception or in IVF outcome confirms the need for sperm function tests to determine optimal management. We reviewed HZA and SPA predictive power in IVF outcome, with statistical significance of diagnostic power of the assays. HZA was readily efficient in predicting IVF outcome, while evident inconsistency among the studies analysed framed the SPA’s role in male fertility evaluation. Considerable variation was noted in the diagnostic accuracy values of SPA with wide sensitivity (52–100%), specificity (0–100%), and PPV (18–100%) and NPV (0–100%) together with fluctuation and notable differentiation in methodology and cutoff values employed by each group. HZA methodology was overall consistent with minor variation in cutoff values and oocyte source, while data analysis reported strong correlation between HZA results with IVF outcome, high sensitivity (75–100%), good specificity (57–100%), and high PPV (79–100%) and NPV (68–100%). HZA correlated well with IVF outcome and demonstrated better sensitivity/specificity and positive/negative predictive power. Males with normal or slightly abnormal semen profiles could benefit by this intervention and could be evaluated prior to referral to assisted reproduction. HZA should be used in a sequential fashion with semen analysis and potentially other bioassays in an IVF setting. Paraskevi Vogiatzi, Charalampos Chrelias, David J. Cahill, Maria Creatsa, Nikos Vrachnis, Zoe Iliodromiti, Demetrios Kassanos, and Charalampos Siristatidis Copyright © 2013 Paraskevi Vogiatzi et al. All rights reserved. Alpha-Lipoic Acid Attenuates Renal Injury in Rats with Obstructive Nephropathy Thu, 03 Oct 2013 18:11:52 +0000 This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on renal injury in obstructive nephropathy. Male Sprague-Dawley rats were assigned into sham-operated unilateral ureteral obstruction (UUO) and UUO treated with ALA groups. ALA 60 mg/kg was injected intraperitoneally 2 days before UUO induction and continued afterward for 7 days. Renal function, oxidative stress markers, nitric oxide, transforming growth factor-1 (TGF-β1), and histological changes were evaluated at the end of the experiment. Obstruction of the ureter resulted in renal dysfunction as indicated by significant increases in blood urea nitrogen and serum creatinine. Nonobstructed contralateral kidneys in all groups examined did not show any morphological or biochemical alterations. In untreated UUO group, the obstructed kidney developed marked hydronephrosis, leukocyte infiltration, and severe interstitial fibrosis. These functional and structural changes were associated with significant increases in tissue levels of malondialdehyde, nitric oxide, and TGF-β1 but decreases in reduced glutathione and total antioxidant capacity. Pretreatment with ALA significantly minimized all the changes elicited by ureteral obstruction. These findings demonstrate that ALA supplementation attenuates renal injury in rats with obstructive nephropathy and further suggest that oxidative stress inhibition is likely to be involved in the beneficial effects of this compound. Orawan Wongmekiat, Dolrawee Leelarungrayub, and Kamthorn Thamprasert Copyright © 2013 Orawan Wongmekiat et al. All rights reserved. Factors Influencing Women's Decision to Participate or Not in a Surgical Randomised Controlled Trial for Surgical Treatment of Female Stress Urinary Incontinence Tue, 17 Sep 2013 18:20:58 +0000 The study aims to explore the potentially influential factors affecting women's decision to accept/decline participation in surgical randomised trial using a novel acceptance/refusal questionnaire (ARQ). All women who were eligible to participate in SIMS-RCT were asked to complete the relevant section (acceptance/refusal) of the ARQ. Women reported its degree of relevance for their decision on a six-point Likert scale (0 = highly irrelevant, 5 = highly relevant). 135 (98%) and 31 (70%) women completed the acceptance and refusal sections of the ARQ, respectively. The most influencing factor in women’s acceptance was the anticipation of “potential personal benefit”; percentage of relevance (POR) was 91.9%, followed by interest in helping others by “supporting innovative medical research”; POR was 87.7%. Most influencing factor in refusal for participation was “do not have time for follow-up”; POR was 56.8%, followed by “do not like the concept of randomisation”; POR was 54.4%. In conclusion, this study identifies the most influential factors relevant to women decision-making whether or not to participate in RCTs assessing surgical interventions for female stress urinary incontinence (SUI). A number of factors leading to refusal of participation are potentially correctable leading to better recruitment rates in future RCTs. Alyaa Mostafa, James N'Dow, and Mohamed Abdel-Fattah Copyright © 2013 Alyaa Mostafa et al. All rights reserved. Coating with Autologous Plasma Improves Biocompatibility of Mesh Grafts In Vitro: Development Stage of a Surgical Innovation Tue, 17 Sep 2013 18:16:15 +0000 Purpose. To investigate mesh coating modalities with autologous blood components in a recently developed in vitro test system for biocompatibility assessment of alloplastic materials. Materials and Methods. Seven different mesh types, currently used in various indications, were randomly investigated. Meshes were coated prior to cultivation with autologous peripheral blood mononuclear cells (PBMCs), platelets, and blood plasma. Pretreated meshes were incubated over 6 weeks in a minced tissue assay, representative for fibroblasts, muscle cells, and endothelial cells originating from 10 different patients. Adherence of those tissues on the meshes was microscopically investigated and semiquantitatively assessed using a previously described scoring system. Results. Coating with peripheral blood mononuclear cells did not affect the adherence score, whereas coating with platelets and blood plasma increased the score suggesting improved biocompatibility in vitro. The previous ranking of native meshes remained consistent after coating. Conclusion. Plasma coating of meshes improves their biocompatibility score in a novel in vitro test system. Holger Gerullis, Evangelos Georgas, Christoph Eimer, Christian Arndt, Dimitri Barski, Bernhard Lammers, Bernd Klosterhalfen, Mihaly Borós, and Thomas Otto Copyright © 2013 Holger Gerullis et al. All rights reserved. Androgen Signaling Disruption during Fetal and Postnatal Development Affects Androgen Receptor and Connexin 43 Expression and Distribution in Adult Boar Prostate Tue, 17 Sep 2013 10:51:48 +0000 To date, limited knowledge exists regarding the role of the androgen signaling during specific periods of development in the regulation of androgen receptor (AR) and connexin 43 (Cx43) in adult prostate. Therefore, in this study we examined mRNA and protein expression, and tissue distribution of AR and Cx43 in adult boar prostates following fetal (GD20), neonatal (PD2), and prepubertal (PD90) exposure to an antiandrogen flutamide (50 mg/kg bw). In GD20 and PD2 males we found the reduction of the luminal compartment, inflammatory changes, decreased AR and increased Cx43 expression, and altered localization of both proteins. Moreover, enhanced apoptosis and reduced proliferation were detected in the prostates of these animals. In PD90 males the alterations were less evident, except that Cx43 expression was markedly upregulated. The results presented herein indicate that in boar androgen action during early fetal and neonatal periods plays a key role in the maintenance of normal phenotype and functions of prostatic cells at adulthood. Furthermore, we demonstrated that modulation of Cx43 expression in the prostate could serve as a sensitive marker of hormonal disruption during different developmental stages. Anna Hejmej, Ewelina Górowska, Małgorzata Kotula-Balak, Katarzyna Chojnacka, Marta Zarzycka, Justyna Zając, and Barbara Bilińska Copyright © 2013 Anna Hejmej et al. All rights reserved. Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma Wed, 04 Sep 2013 14:48:52 +0000 Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents. Alessandro Conti, Matteo Santoni, Consuelo Amantini, Luciano Burattini, Rossana Berardi, Giorgio Santoni, Stefano Cascinu, and Giovanni Muzzonigro Copyright © 2013 Alessandro Conti et al. All rights reserved. High Expression of H3K27me3 Is an Independent Predictor of Worse Outcome in Patients with Urothelial Carcinoma of Bladder Treated with Radical Cystectomy Wed, 04 Sep 2013 10:00:32 +0000 It has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression pattern of H3K27me3 and its clinicopathological/prognostic significance in urothelial carcinoma of bladder (UCB) are unclear. In this study, upregulated expression of H3K27me3 protein was observed in the majority of UCBs by Western blotting. High expression of H3K27me3 was examined by IHC in 59/126 (46.8%) of UCB tissues and in 18/72 (25.0%) of normal urothelial bladder epithelial tissues (). High expression of H3K27me3 was associated with multifocal tumors and lymph node metastases (). Patients with high expression of H3K27me3 had shorter cancer-specific survival (CSS) time than patients with low expression of H3K27me3 (). In different subsets of UCB patients, high expression of H3K27me3 was also a prognostic indicator in patients with grade 2 and grade 3, pT1, pT2, pT3, and pN− disease (). Importantly, expression of H3K27me3 was an independent predictor for CSS () of UCB patients treated with radical cystectomy (RC). Our data suggests that high expression of H3K27me3 is an independent molecular marker for predicting poor prognosis of UCB patients treated with RC. Jianye Liu, Yonghong Li, Yiji Liao, Shijuan Mai, Zhiling Zhang, Zhouwei Liu, Lijuan Jiang, Yixin Zeng, Fangjian Zhou, and Dan Xie Copyright © 2013 Jianye Liu et al. All rights reserved. Hyperthermia as Adjunct to Intravesical Chemotherapy for Bladder Cancer Sun, 01 Sep 2013 10:47:20 +0000 Nonmuscle invasive bladder cancer remains a very costly cancer to manage because of high recurrence rates requiring long-term surveillance and treatment. Emerging evidence suggests that adjunct and concurrent use of hyperthermia with intravesical chemotherapy after transurethral resection of bladder tumor further reduces recurrence risk and progression to advanced disease. Hyperthermia has both direct and immune-mediated cytotoxic effect on tumor cells including tumor growth arrest and activation of antitumor immune system cells and pathways. Concurrent heat application also acts as a sensitizer to intravesical chemotherapy agents. As such the ability to deliver hyperthermia to the focus of tumor while minimizing damage to surrounding benign tissue is of utmost importance to optimize the benefit of hyperthermia treatment. Existing chemohyperthermia devices that allow for more localized heat delivery continue to pave the way in this effort. Current investigational methods involving heat-activated drug delivery selectively to tumor cells using temperature-sensitive liposomes also offer promising ways to improve chemohyperthermia efficacy in bladder cancer while minimizing toxicity to benign tissue. This will hopefully allow more widespread use of chemohyperthermia to all bladder cancer patients, including metastatic bladder cancer. Richmond A. Owusu, Michael R. Abern, and Brant A. Inman Copyright © 2013 Richmond A. Owusu et al. All rights reserved. A Novel Technique of Ultra-Mini-Percutaneous Nephrolithotomy: Introduction and an Initial Experience for Treatment of Upper Urinary Calculi Less Than 2 cm Wed, 24 Jul 2013 11:35:10 +0000 Objectives. To describe our novel modified technique of ultra-mini-percutaneous nephrolithotomy (UMP) using of a novel 6 Fr mininephroscope through an 11–13 Fr metal sheath to perform holmium: YAG laser lithotripsy. Methods. The medical records of 36 patients with moderate-sized (<20 mm) kidney stones treated with UMP from April to July 2012 were retrospectively reviewed. Patients were assessed at the 1st day and 1st month postoperatively by KUB and US to assess stone-free status. Results. The mean stone size was 14.9 ± 4.1 mm (rang: 6–20). The average operative time was 59.8 ± 15.9 (30–90) min. The stone-free rate at postoperative 1st day and 1st month was 88.9% and 97.2%. The mean hospital stay was 3.0 ± 0.9 (2–5) days. Complications were noted in 6 (16.7%) cases according to the Clavien classification, including sepsis in 2 (5.6%) cases (grade II), urinary extravasations in 1 (2.8%) case (grade IIIa), and fever in 3 (8.3%) cases (grade II). No patients needed blood transfusion. Conclusions. UMP is technically feasible, safe, and efficacious for moderate-sized renal stones with an advantage of high stone-free rates and low complication rates. However, due to the limits of its current unexplored indications, UMP is therefore a supplement to, not a substitute for, the standard mini-PCNL technology. Janak Desai, Guohua Zeng, Zhijian Zhao, Wen Zhong, Wenzhong Chen, and Wenqi Wu Copyright © 2013 Janak Desai et al. All rights reserved. Sperm Impairment by Sperm Agglutinating Factor Isolated from Escherichia coli: Receptor Specific Interactions Wed, 17 Jul 2013 12:51:46 +0000 In an earlier work done in our laboratory, we have been able to isolate a sperm agglutinating strain of Escherichia coli from the semen sample of a male attending infertility clinic. Further, factor responsible for sperm agglutination (SAF) was isolated and purified, and, using SAF as a tool, corresponding SAF binding receptor from human spermatozoa has been purified. Characterization of SAF and SAF binding receptor using MALDI-TOF showed homology to glutamate decarboxylase and MHC class I molecule, respectively. Coincubation of SAF with spermatozoa not only resulted in spermagglutination but could also compromise other sperm parameters, namely, Mg2+ dependent ATPase activity and apoptosis. Intravaginal administration of SAF could lead to infertility in Balb/c mice. SAF induced impairment of sperm parameters, and infertility was observed to be due to interaction of SAF with sperm surface receptor component as, when purified receptor was introduced, receptor completely inhibited all the detrimental effects induced by SAF. From these results, it could be concluded that interaction of SAF with spermatozoa is receptor mediated. Kiranjeet Kaur and Vijay Prabha Copyright © 2013 Kiranjeet Kaur and Vijay Prabha. All rights reserved. Sexual Function in Women with Stress Urinary Incontinence Treated with the SPARC Sling System Sun, 14 Jul 2013 10:40:02 +0000 Aim. To evaluate the impact of SPARC on female sexual function. Methods. 151 women with a mean age of and SUI had a complete urodynamic investigation and underwent SPARC operation. 98 women completed the validated female sexual function index questionnaire (FSFI) at baseline and 94 women at follow-up. A minimum follow-up of 12 months was required for study inclusion. Results. 52/98 women were sexually active at baseline. Postoperatively only 33 patients were sexually active. The FSFI score of all 33 pre- and postoperative sexually active women increased from at baseline to at follow-up (). Scores of women with reduced sexual function at baseline increased significantly in the domains desire, arousal, and lubrication as well as orgasm and satisfaction and total FSFI-score () postoperatively. Conclusions. Our results suggest that the SPARC-sling procedure for SUI did not negatively interfere with female sexual function. Badereddin Mohamad Al-Ali, Rany Shamloul, Georg C. Hutterer, Erika Puchwein, Karl Pummer, Alexander Avian, and Günter Primus Copyright © 2013 Badereddin Mohamad Al-Ali et al. All rights reserved. Near-Infrared Spectroscopy of the Urinary Bladder during Voiding in Men with Lower Urinary Tract Symptoms: A Preliminary Study Sun, 14 Jul 2013 10:21:53 +0000 Objectives. To determine the difference in response of NIRS of the bladder during voiding between men with and without BOO.LUTS. Methods. A prospective, case series, study included 36 men with LUTS. Patients completed the IPSS questionnaire; prostate volumes were measured sonographically. Patients underwent pressure flow study (PFS) with simultaneous NIRS of the bladder. Amplitudes of HHb, O2Hb, and were calculated at , relative to baseline. Patients were urodynamically classified as obstructed and unobstructed. Recursive partition analysis (RPA) was performed to reclassify patients using NIRS amplitudes, followed by combined data of NIRS amplitudes, prostate volume, IPSS, and to determine the best predictor(s) of BOO. Results. PFS classified 28 patients as obstructed and 8 as unobstructed. The median HHb amplitude was significantly higher in obstructed group. RPA of NIRS amplitudes correctly reclassified 89% of patients [AUC: 0.91]. RPA of the combined IPSS, prostate volume, PVR, and correctly reclassified 72% of patients [AUC: 0.84]. When NIRS amplitudes were added to this combination, RPA revealed a significantly () higher rate of correct reclassification in 89% of patients with 89.3% sensitivity and 88% specificity for obstruction [AUC: 0.96]. Conclusion. NIRS data can be of diagnostic value for BOO in men with LUTS. Fawzy F. Farag, Joseph Meletiadis, Mohamad D. Saleem, Wout F. Feitz, and John P. Heesakkers Copyright © 2013 Fawzy F. Farag et al. All rights reserved. Prevalence Rate and Risk Factors of Depression in Outpatients with Premature Ejaculation Sat, 15 Jun 2013 17:43:07 +0000 The purpose of this study is to investigate the prevalence rate and risk factors of depression in outpatients who were diagnosed with PE. Therefore, between September 2009 and September 2011, 1801 outpatients at andrology clinics were enrolled and consented to participate in our survey by completed a verbal questionnaire. It included the following: (1) demographic data (e.g., age, body mass index), (2) PE duration, medical history, and sexual history, (3) self-estimated intravaginal ejaculatory latency times, (4) the Zung Self-rating Depression Scale (SDS), and (5) the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and (6) the International Index of Erectile Function (IIEF-5). The results showed that a total of 1,206 patients were diagnosed with PE. The prevalence rate of depression in these PE patients was 26.78%. Depression was associated with PE duration, NIH-CPSI score, and IIEF-5 score. Risk factors for depression specifically included PE durations for 13–24, 25–60, or ≥61 months, CPSI scores of 15–30 or ≥31, and IIEF-5 scores <22. These findings suggested that several associated factors (PE duration, CPSI scores, and IIEF-5 scores) were the risk factors of depression in men with PE. Xiansheng Zhang, Jingjing Gao, Jishuang Liu, Lei Xia, Jiajia Yang, Zongyao Hao, Jun Zhou, and Chaozhao Liang Copyright © 2013 Xiansheng Zhang et al. All rights reserved. Comparison of Prostate-Specific Promoters and the Use of PSP-Driven Virotherapy for Prostate Cancer Thu, 31 Jan 2013 08:49:57 +0000 Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in men today. Although virus-based gene therapy is a promising strategy to combat advanced prostate cancer, its current effectiveness is limited partially due to inefficient cellular transduction in vivo. To overcome this obstacle, conditional oncolytic viruses (such as conditional replication adenovirus (CRAD)) are developed to specifically target prostate without (or with minimal) systemic toxicity due to viral self-replication. In this study, we have analyzed and compared three prostate-specific promoters (PSA, probasin, and MMTV LTR) for their specificity and activity both in vitro and in vivo. Both mice model with xenograft prostate tumor model and canine model were used. The best PSP was selected to construct a prostate-specific oncolytic adenovirus (CRAD) by controlling the adenoviral E1 region. The efficacy and specificity of CRAD on prostate cancer cells were examined in cell culture and animal models. Yi Lu, Yu Zhang, Guimin Chang, and Jun Zhang Copyright © 2013 Yi Lu et al. All rights reserved. Mechanism of Growth Inhibition of Prostate Cancer Xenografts by Valproic Acid Tue, 02 Oct 2012 13:22:32 +0000 Valproic Acid (VPA), a histone deacetylase inhibitor, has been demonstrated to cause a marked decrease in proliferation of prostate cancer (PCa) cells in vitro and a significant reduction in tumor volume in vivo. The goal of this study is to better understand the VPA-induced growth inhibition in vivo, by studying expression of various markers in PCa xenografts. Methods. For in vitro experiments, PCa cells were treated with 0, 0.6, and 1.2 mM VPA for 14 days. For in vivo models, experimental animals received 0.4% VPA in drinking water for 35 days. Tissue microarray was generated using cell pellets and excised xenografts. Results. VPA treatment causes cell cycle arrest in PCa cells in vivo, as determined by increase in p21 and p27 and decrease in cyclin D1 expression. Increased expression of cytokeratin18 was also seen in xenografts. LNCaP xenografts in treated animals had reduced androgen receptor (AR) expression. While decreased proliferation was found in vitro, increase in apoptosis was found to be the reason for decreased tumor growth in vivo. Also, an anti-angiogenic effect was observed after VPA treatment. Conclusion. VPA inhibits tumor growth by multiple mechanisms including cell cycle arrest, induction of differentiation, and inhibition of growth of tumor vasculature. Abhinav Sidana, Muwen Wang, Shabana Shabbeer, Wasim H. Chowdhury, George Netto, Shawn E. Lupold, Michael Carducci, and Ronald Rodriguez Copyright © 2012 Abhinav Sidana et al. All rights reserved. No Evidence for Statin-induced Proteinuria in Healthy Volunteers as Assessed by Proteomic Analysis Tue, 13 Sep 2011 10:32:45 +0000 In clinical studies of statins (class of drugs lowering plasma cholesterol levels), transient low-molecular-weight proteinuria was observed. The causes of statin-induced proteinuria in the patient background of those studies (cardiovascular and kidney disease) are multifactorial and, therefore, a matter of debate. In light of this, it seemed interesting to investigate the effect of statins on the urinary protein concentration and proteome in healthy volunteers. Six healthy volunteers were randomly treated with rosuvastatin (40 mg/day) or pravastatin (80 mg/day) in a double-blinded cross-over study. Total urinary protein concentration and the concentration of albumin/retinol-binding protein were analysed, after which the urinary proteome was investigated. From the results described in this study, it was concluded that statins do not induce major changes in the urinary protein concentration/proteome. High variability in the baseline urinary proteome/proteins among volunteers, however, made it very difficult to find subtle (possibly isolated to individuals) effects of statins. Anja Verhulst, Hilde Geryl, and Patrick D'Haese Copyright © 2011 Anja Verhulst et al. All rights reserved. A Metabonomic Comparison of Urinary Changes in Zucker and GK Rats Wed, 13 Oct 2010 13:20:41 +0000 To further investigate pathogenesis and pathogenic process of type 2 diabetes mellitus (T2DM), we compared the urinary metabolic profiling of Zucker obese and Goto-kakizaki (GK) rats by NMR-based metabonomics. Principal component analysis (PCA) on urine samples of both models rats indicates markedly elevated levels of creatine/creatinine, dimethylamine, and acetoacetate, with concomitantly declined levels of citrate, 2-ketoglurarate, lactate, hippurate, and succinate compared with control rats, respectively. Simultaneously, compared with Zucker obese rats, the GK rats show decreased levels of trimethylamine, acetate, and choline, as well as increased levels of creatine/creatinine, acetoacetate, alanine, citrate, 2-ketoglutarate, succinate, lactate, and hippurate. This study demonstrates metabolic similarities between the two stages of T2DM, including reduced tricarboxylic acid (TCA) cycle and increased ketone bodies production. In addition, compared with Zucker obese rats, the GK rats have enhanced concentration of energy metabolites, which indicates energy metabolic changes produced in hyperglycemia stage more than in insulin resistance stage. Liang-Cai Zhao, Xiao-Dong Zhang, Shi-Xian Liao, Hong-Chang Gao, He-Yao Wang, and Dong-Hai Lin Copyright © 2010 Liang-Cai Zhao et al. All rights reserved. The Immunoexpression of FSH-R in the Ductuli Efferentes and the Epididymis of Men and Rat: Effect of FSH on the Morphology and Steroidogenic Activity of Rat Epididymal Epithelial Cells In Vitro Wed, 12 May 2010 11:09:03 +0000 The Sertoli cells were regarded as the only target for FSH in male reproductive system. The expression of FSH receptor (FSH-R) was detected also in epithelial cells of the caput epididymis of rat and monkey. We showed in the immunohistochemistry study the expression of FSH-R in rat and human ductuli efferentes and the caput, corpus, and cauda epididymis, moreover, by Western blot analysis in the caput and cauda epididymis of rat. Additionally, we presented that the morphology of rat epididymal epithelial cells in vitro was affected by FSH, and FSH stimulation resulted in the increase of 17-estradiol synthesis by rat caput epididymal cells in dose-depended manner. In conclusion, the identification of FSH receptors in human and rat epididymides supports our results that the epididymis is a target organ not only for LH but additionally for FSH. On the basis of the results we showed for the first time that morphology of epididymal epithelial cells and epididymal steroidogenesis can be regulated by FSH. Małgorzata Świder-Al-Amawi, Agnieszka Kolasa, Andrzej Sikorski, Mariola Marchlewicz, Irena Baranowska-Bosiacka, and Barbara Wiszniewska Copyright © 2010 Małgorzata Świder-Al-Amawi et al. 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