BioMed Research International: Urology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. New Insights into Diagnosis and Treatment of Renal Cell Carcinoma, Bladder Cancer, and Prostate Cancer Mon, 13 Mar 2017 08:11:27 +0000 Piotr L. Chlosta, Tomasz Golabek, and Péter Nyirády Copyright © 2017 Piotr L. Chlosta et al. All rights reserved. Ethyl Acetate Extracts of Semen Impatientis Inhibit Proliferation and Induce Apoptosis of Human Prostate Cancer Cell Lines through AKT/ERK Pathways Mon, 13 Mar 2017 00:00:00 +0000 Objective. To investigate the inhibitory effect of ethyl acetate extracts of Impatiens balsamina L. on prostate cancer cells. Methods. Impatiens balsamina L. was extracted to get water, ethanol, oil ether, ethyl acetate, and butanol extracts. CCK-8 assay was used to detect the inhibitory effect. Apoptosis rates and cell cycle distribution were detected by flow cytometry. Transwell assay was performed to test the ability of migration. The expressions of Bcl-2, Bax, cleaved-caspase-3, p-ERK, ERK, p-AKT, AKT, cyclin D1, cyclin E, and MMP2 were detected by Western blot. Results. Ethyl acetate extracts had the strongest inhibitory effect. After being treated with different concentrations of ethyl acetate extracts, the percentage of G0/G1 phase increased significantly, cyclin D1 and cyclin E expression decreased, apoptosis rate was significantly higher, and the ability of migration of PC-3 and RV1 was inhibited significantly. Western blot showed that the expressions of Bcl-2, p-ERK, and p-AKT were significantly decreased, but the expressions of Bax and caspase-3 cleavage were increased. Conclusions. Impatiens balsamina L. inhibited the proliferation of human prostate cancer cells; ethyl acetate extracts have the strongest effect. It could inhibit cell proliferation and migration, cause G1 phase arrest, and induce apoptosis probably through inhibition of the AKT and ERK pathways. Tao Wang, Yang Cai, Wen Song, Ruibao Chen, Dunmei Hu, Jianhan Ye, Lu Liu, Wei Peng, Junfeng Zhang, Shaogang Wang, Weiming Yang, Jihong Liu, and Yufeng Ding Copyright © 2017 Tao Wang et al. All rights reserved. Evidence in Urologic- and Pelvic-Surgery Research: Finding the IDEAL Way of Reporting Thu, 09 Mar 2017 00:00:00 +0000 H. Gerullis, D. Barski, P. U. Malmström, X. Sun, and T. H. Ecke Copyright © 2017 H. Gerullis et al. All rights reserved. Antiurolithiasis Activity of Bioactivity Guided Fraction of Bergenia ligulata against Ethylene Glycol Induced Renal Calculi in Rat Thu, 02 Mar 2017 08:02:47 +0000 Dried rhizome of Bergenia ligulata (pashanbhed) is commonly used as a traditional herbal medicine with a wide range of therapeutic applications including urolithiasis. Aqueous extract of B. ligulata was prepared through maceration followed by decoction (mother extract, 35.9% w/w). Further, polarity based fractions were prepared successively from mother extract which yielded 3.4, 2.9, 5.4, 7.5, and 11.3% w/w of hexane, toluene, dichloromethane (DCM), -butanol, and water fractions, respectively. The in vitro, ex vivo, and real-time antiurolithiasis activity of mother extract and fractions were carried out using aggregation assay in synthetic urine and in rat plasma. The study revealed that DCM fraction has significantly () greater inhibitory potential than other fractions. Ethylene glycol in drinking water (0.75%, v/v) for 28 days was used for induction of urolithiasis and the curative effects of mother extract and DCM fraction were checked for the level of oxalate, calcium, creatinine, uric acid, and urea of both urine and serum. Treatment with mother extract and DCM fraction at a dose of 185 mg/kg and 7 mg/kg, respectively, in ethylene glycol induced rats resulted in a significant () decrease in serum and urine markers. Histological study revealed lower number of calcium oxalate deposits with minimum damage in the kidneys of mother extract and DCM fraction treated rats. This result provides a scientific basis for its traditional claims. Ikshit Sharma, Washim Khan, Rabea Parveen, Md. Javed Alam, Iftekhar Ahmad, Mohd Hafizur Rehman Ansari, and Sayeed Ahmad Copyright © 2017 Ikshit Sharma et al. All rights reserved. Urethral Reconstruction Using Mesothelial Cell-Seeded Autogenous Granulation Tissue Tube: An Experimental Study in Male Rabbits Tue, 28 Feb 2017 08:04:30 +0000 Objective. This study was to evaluate the utility of the compound graft for tubularized urethroplasty by seeding mesothelial cells onto autogenous granulation tissue. Methods. Silastic tubes were implanted subcutaneously in 18 male rabbits, of which nine underwent omentum biopsies simultaneously for in vitro expansion of mesothelial cells. The granulation tissue covering the tubes was harvested 2 weeks after operation. Mesothelial cells were seeded onto and cocultured with the tissue for 7 days. A pendulous urethral segment of 1.5 cm was totally excised. Urethroplasty was performed with mesothelial cell-seeded tissue tubes in an end-to-end fashion in nine rabbits and with unseeded grafts in others as controls. Serial urethrograms were performed at 1, 2, and 6 months postoperatively. Meanwhile, the neourethra was harvested and analyzed grossly and histologically. Results. Urethrograms showed cell-seeded grafts maintained wide at each time point, while strictures formation was found in unseeded grafts. Histologically, layers of urothelium surrounded by increasingly organized smooth muscles were observed in seeded grafts. In contrast, myofibroblasts accumulation and extensive scarring occurred in unseeded grafts. Conclusions. Mesothelial cell-seeded granulation tissue tube can be successfully used for tubularized urethroplasty in male rabbits. Shiwei Jiang, Zhonghua Xu, Yuanyuan Zhao, Lei Yan, Zunlin Zhou, and Gangli Gu Copyright © 2017 Shiwei Jiang et al. All rights reserved. Female Functional Constipation Is Associated with Overactive Bladder Symptoms and Urinary Incontinence Tue, 28 Feb 2017 06:43:34 +0000 This noninterventional cross-sectional study aims to assess the association between functional constipation (FC) and urinary symptoms in female patients with no treatment for urination and defecation. The Rome III criteria for evaluation of defecation, Overactive Bladder Symptom Score (OABSS) for evaluation of urinary symptoms, and clinical features were investigated in 145 female patients. Latent FC and moderate to severe overactive bladder (OAB) were defined on the basis of positivity for two or more of the Rome III criteria and an OABSS ≥ 6 with OABSS Q3 ≥ 2, respectively. In 60 latent FC patients, the OABSS was higher (5.0 versus 3.2, ), and concurrent moderate to severe OAB symptoms and OAB with urinary incontinence were more frequent than those in 85 nonlatent FC patients (33.3 versus 10.6%, , and 31.7 versus 7.1%, ). Multivariate analysis demonstrated that moderate to severe OAB symptoms were a significant associated factor of latent FC (odds ratio (OR) = 4.125, ), while latent FC was the only associated factor of moderate to severe OAB and OAB with urinary incontinence (OR = 4.227, and OR = 4.753, ). In conclusion, moderate to severe OAB symptoms are correlated with FC. Moreover, FC is related to moderate to severe OAB symptoms and to OAB with urinary incontinence. Takahiro Maeda, Masuomi Tomita, Atsushi Nakazawa, Gen Sakai, Shinsuke Funakoshi, Akari Komatsuda, Yujiro Ito, Hirohiko Nagata, Nobuhiro Tsukada, and So Nakamura Copyright © 2017 Takahiro Maeda et al. All rights reserved. Physical Exercise and Patients with Chronic Renal Failure: A Meta-Analysis Mon, 20 Feb 2017 06:52:55 +0000 Chronic renal failure is a severe clinical problem which has some significant socioeconomic impact worldwide and hemodialysis is an important way to maintain patients’ health state, but it seems difficult to get better in short time. Considering these, the aim in our research is to update and evaluate the effects of exercise on the health of patients with chronic renal failure. The databases were used to search for the relevant studies in English or Chinese. And the association between physical exercise and health state of patients with chronic renal failure has been investigated. Random-effect model was used to compare the physical function and capacity in exercise and control groups. Exercise is helpful in ameliorating the situation of blood pressure in patients with renal failure and significantly reduces VO2 in patients with renal failure. The results of subgroup analyses show that, in the age >50, physical activity can significantly reduce blood pressure in patients with renal failure. The activity program containing warm-up, strength, and aerobic exercises has benefits in blood pressure among sick people and improves their maximal oxygen consumption level. These can help patients in physical function and aerobic capacity and may give them further benefits. Zhenzhen Qiu, Kai Zheng, Haoxiang Zhang, Ji Feng, Lizhi Wang, and Hao Zhou Copyright © 2017 Zhenzhen Qiu et al. All rights reserved. Long-Term Oncological Outcomes for Young Men Undergoing Radical Prostatectomy for Localized Prostate Cancer Sun, 19 Feb 2017 00:00:00 +0000 Aim. The aim of this study was to describe PCa characteristics and long-term outcomes in young men aged ≤55 years after radical prostatectomy (RP) and to compare them with older men cohort. Methods. Among 2,200 patients who underwent RP for clinically localized PCa at our centre between 2001 and 2015, 277 (10.3%) men aged ≤55 years were identified. All preoperative and pathological parameters were compared between groups. Biochemical progression free survival (BPFS) and disease progression free survival (DPFS) were assessed at 5 and 10 years. Results. Men aged ≤55 years had similar pathological tumor characteristics and biochemical recurrence rate (BCR) compared to their older counterparts. Disease progression rate 2.5% versus 0.4% was higher in older patients (). BPFS rate was not different in both study groups. Estimated 10-year DPFS was 98.8% in younger men compared to 89.2% in their older counterparts (). Multivariate Cox regression showed that Gleason score lymph-nodes and surgical margins status were significant predictors for disease progression. Conclusions. In our cohort, men aged ≤55 years had similar pathological PCa characteristics and BCR rate in comparison with older men. RP can be performed with excellent long-term DPFS results in men with localized PCa at ≤55 years of age. Daimantas Milonas, Zilvinas Venclovas, Inga Gudinaviciene, Kristina Zviniene, and Aivaras Jonas Matjosaitis Copyright © 2017 Daimantas Milonas et al. All rights reserved. Urinary Biomarker Panel to Improve Accuracy in Predicting Prostate Biopsy Result in Chinese Men with PSA 4–10 ng/mL Wed, 15 Feb 2017 13:09:47 +0000 This study aims to evaluate the effectiveness and clinical performance of a panel of urinary biomarkers to diagnose prostate cancer (PCa) in Chinese men with PSA levels between 4 and 10 ng/mL. A total of 122 patients with PSA levels between 4 and 10 ng/mL who underwent consecutive prostate biopsy at three hospitals in China were recruited. First-catch urine samples were collected after an attentive prostate massage. Urinary mRNA levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The predictive accuracy of these biomarkers and prediction models was assessed by the area under the curve (AUC) of the receiver-operating characteristic (ROC) curve. The diagnostic accuracy of PCA3, PSGR, and MALAT-1 was superior to that of PSA. PCA3 performed best, with an AUC of 0.734 (95% CI: 0.641, 0.828) followed by MALAT-1 with an AUC of 0.727 (95% CI: 0.625, 0.829) and PSGR with an AUC of 0.666 (95% CI: 0.575, 0.749). The diagnostic panel with age, prostate volume, % fPSA, PCA3 score, PSGR score, and MALAT-1 score yielded an AUC of 0.857 (95% CI: 0.780, 0.933). At a threshold probability of 20%, 47.2% of unnecessary biopsies may be avoided whereas only 6.2% of PCa cases may be missed. This urinary panel may improve the current diagnostic modality in Chinese men with PSA levels between 4 and 10 ng/mL. Yongqiang Zhou, Yun Li, Xiangnan Li, and Minjun Jiang Copyright © 2017 Yongqiang Zhou et al. All rights reserved. Protective Effects of the Segmental Renal Artery Clamping Technique on Ischemia-Reperfusion Injury in db/db Diabetic Mice Sun, 12 Feb 2017 00:00:00 +0000 Renal ischemia-reperfusion (I/R) injury is inevitable in partial nephrectomy and other kidney surgeries, with a higher incidence in patients with renal insufficiency. This study aimed to investigate the protective effects of precise segmental renal artery clamping (SRAC) against renal I/R injury in db/db diabetic mice, compared with conventional renal artery clamping (RAC). Grape seed extract, a powerful free radical scavenger, was administered to diabetic mice for 4 weeks before operation in subgroups (30 mg/kg/d). The unilateral renal pedicle was ligatured, and I/R injury to the contralateral kidney was induced (ischemia for 30 min followed by reperfusion for 24 h). Blood glucose value, creatinine, blood urea nitrogen, and urine microalbumin/urine creatinine ratio increased gradually and showed no preoperative statistical differences among six subgroups. These parameters were significantly lower in the SRAC than in the RAC group 24 h postoperatively. Moreover, the nonischemic area in the SRAC group expressed less KIM-1 and TNF- mRNA and also revealed minor histopathological damage induced by I/R. These findings suggest that SRAC effectively reduces early renal injury induced by I/R and accelerates the recovery of renal function in diabetic mice. Thus, SRAC may be an ideal technique in partial nephrectomy, especially for patients with diabetic nephropathy and other renal insufficiencies. Chao Liang, Jundong Zhu, Chenkui Miao, Shangqian Wang, Lei Zhang, Pu Li, Zengjun Wang, and Pengfei Shao Copyright © 2017 Chao Liang et al. All rights reserved. Silencing CAPN2 Expression Inhibited Castration-Resistant Prostate Cancer Cells Proliferation and Invasion via AKT/mTOR Signal Pathway Thu, 09 Feb 2017 00:00:00 +0000 The mRNA expression of CAPN2 was upregulated in CRPC cells (DU145 and PC3) than that in non-CRPC cells. Silencing CAPN2 expression could inhibit DU145 and PC3 cells proliferation by cell cycle arrest at G1 phase. Knockdown of CPAN2 level suppressed the migration and invasion capacity of CRPC cells by reducing matrix metalloproteinase-2 (MMP-2) and MMP-9 activation, as well as repressing the phosphorylation protein expression of AKT and mTOR. In addition, we found that the expression of CAPN2 was elevated in Pca tissues than that in normal control tissues. Therefore, we showed the important roles of CAPN2 in the development and progression in CRPC cells, suggesting a new therapeutic intervention for treating castration-resistant prostate cancer patients. Pu Li, Chenkui Miao, Chao Liang, Pengfei Shao, Zengjun Wang, and Jie Li Copyright © 2017 Pu Li et al. All rights reserved. Are the Pathological Characteristics of Prostate Cancer More Aggressive or More Indolent Depending upon the Patient Age? Tue, 07 Feb 2017 00:00:00 +0000 Purpose. To identify pathological characteristics of prostate cancer according to patient age at diagnosis. Methods. A retrospective review of 2,929 men diagnosed with prostate cancer was performed. Pathological characteristics were compared across age groups: ≤55, 56–75, and >75 years. Results. The study cohort included 133 patients (4.5%), 2,033 patients (69.5%), and 763 patients (26.0%) in the three age groups, respectively. The median pathological Gleason sums in the three age groups were 8, 7, and 8, respectively. The Gleason sum, primary Gleason score, and second primary Gleason score were significantly different among the three age groups (, ; , ; , , resp.). The percentages of Gleason pattern 5 tumors for the three age groups were 44.4%, 32.3%, and 36.8%, respectively; they were significantly different (, ). The percentages of tumors with Gleason score grade groups 3–5 for the three age groups were 66.9%, 60.5%, and 66.3%, respectively; they were significantly different (, ). Conclusions. The present study indicated that men aged ≤55 years or >75 years show higher levels of clinically significant prostate cancer compared to patients between the ages of 55 and 75 years. Younger and more elderly male patients are more likely to have a more aggressive disease. Guangjie Ji, Cong Huang, Gang Song, Gengyan Xiong, Dong Fang, He Wang, Han Hao, Lin Cai, Qun He, Zhisong He, and Liqun Zhou Copyright © 2017 Guangjie Ji et al. All rights reserved. The Long-Term Effect of Radical Prostatectomy on Erectile Function, Urinary Continence, and Lower Urinary Tract Symptoms: A Comparison to Age-Matched Healthy Controls Sun, 05 Feb 2017 00:00:00 +0000 Introduction. To analyze the impact of radical prostatectomy (RPE) on erectile function and lower urinary tract function in comparison to age-matched healthy men. Materials and Methods. Patients who underwent radical retropubic prostatectomy completed questionnaires containing the IIEF-5, the Bristol female LUTS questionnaire, and the International Prostate Symptom Score (IPSS). Results. Patients after RPE were included (). Age-matched healthy men () were included. The mean IIEF-5 of patients aged 61–70 yrs after RPE was versus in the control cohort; the respective values for men aged 71–80 yrs after RPE were versus in the control cohort. Urinary incontinence after RPE was reported in 41.9% (61–70 years) and 37.7% (71–80) versus 7.5% and 15.1% in the control cohort. The mean IPSS of patients after RPE aged 61–70 yrs was versus in the control cohort; the respective values for men aged 71–80 yrs were versus in the healthy cohort. Conclusions. The negative effect of radical prostatectomy on erectile and urinary incontinence remains substantial. The physiologically declining erectile and lower urinary tract function with ageing reduces the difference between healthy men and those after surgery. Healthy men have a higher IPSS presumably due to the presence of bladder outlet obstruction. Badereddin Mohamad Al-Ali, Anton Ponholzer, Herbert Augustin, Stephan Madersbacher, and Karl Pummer Copyright © 2017 Badereddin Mohamad Al-Ali et al. All rights reserved. The Evaluation of Risk Factors for Postoperative Infectious Complications after Percutaneous Nephrolithotomy Thu, 02 Feb 2017 07:15:44 +0000 This study was to evaluate the risk factors of infectious complications after percutaneous nephrolithotomy (PCNL) and build a prediction tool for postoperative complications based on the risk factors. A total of 110 male (67.1%) and 54 female (32.9%) patients who underwent PCNL for renal stones between 2010 and 2014 in our institute were included. A detailed clinical information and laboratory results were obtained from patients. Systemic inflammatory response syndrome (SIRS) and postoperative fever were recorded after PCNL surgery. In all, 45 cases (27.4%) developed SIRS and fever was observed in 20 cases (12.2%). In multivariate analysis, stone size (odds ratio, OR = 1.471, ) and urine white blood cell (WBC) (OR = 1.001, ) were related to the development of SIRS. Stone size (OR = 1.644, ), urine WBC (OR = 1.001, ) and serum albumin (OR = 0.807, ) were associated with postoperative fever. We concluded that patients with larger stone size and preoperative urinary tract infection might have a higher risk of developing SIRS and fever after operation, while a high-normal level of serum albumin might be the protective factor for postoperative fever. Tian Yang, Shenghua Liu, Jimeng Hu, Lujia Wang, and Haowen Jiang Copyright © 2017 Tian Yang et al. All rights reserved. Preoperative Gamma-Glutamyltransferase Is Associated with Cancer-Specific Survival and Recurrence-Free Survival of Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus Wed, 11 Jan 2017 07:15:19 +0000 Introduction. To evaluate the prognostic significance of preoperative gamma-glutamyltransferase (GGT) on the subgroup of nonmetastatic renal cell carcinoma (RCC) with venous tumor thrombus. Materials and Methods. We retrospectively reviewed the institutional database and collected the medical data of 156 patients with nonmetastatic RCC with venous tumor thrombus between March 2004 and December 2014. Kaplan-Meier and Cox regression analyses were applied to determine the prognostic factors for cancer-specific survival (CSS) and recurrence-free survival (RFS). Results. The median value and optimal cutoff point of preoperative GGT were 23.0 and 37.5 IU/L, respectively. In the entire cohort, 67 (42.9%) patients experienced disease recurrence, and 46 (29.5%) patients died. Kaplan-Meier analysis revealed that the CSS and RFS rates were lower in patients with preoperative GGT ≥ 37.5 IU/L than in those with preoperative GGT < 37.5 IU/L. Multivariate Cox proportional hazard analysis demonstrated that high preoperative GGT was significantly associated with shorter CSS (hazard ratio [HR]: 2.115; 95% CI: 1.164–3.843; ) and RFS (HR: 1.955; 95% CI: 1.166–3.276; ), after adjusting other covariates. Conclusions. Preoperative GGT can serve as an independent prognostic biomarker of nonmetastatic RCC patients with venous tumor thrombus. Further prospective study is warranted to confirm our results. Cheng Luo, Ben Xu, Yu Fan, Wei Yu, Qian Zhang, and Jie Jin Copyright © 2017 Cheng Luo et al. All rights reserved. Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis Thu, 05 Jan 2017 06:11:43 +0000 Background. Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods. An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results. A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions. Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy. Yuejun Tian, Mei Hong, Suoshi Jing, Xingchen Liu, Hanzhang Wang, Xinping Wang, Dharam Kaushik, Ronald Rodriguez, and Zhiping Wang Copyright © 2017 Yuejun Tian et al. All rights reserved. Prostate Cancer Radiation Therapy: What Do Clinicians Have to Know? Wed, 28 Dec 2016 14:49:53 +0000 Radiotherapy (RT) for prostate cancer (PC) has steadily evolved over the last decades, with improving biochemical disease-free survival. Recently population based research also revealed an association between overall survival and doses ≥ 75.6 Gray (Gy) in men with intermediate- and high-risk PC. Examples of improved RT techniques are image-guided RT, intensity-modulated RT, volumetric modulated arc therapy, and stereotactic ablative body RT, which could facilitate further dose escalation. Brachytherapy is an internal form of RT that also developed substantially. New devices such as rectum spacers and balloons have been developed to spare rectal structures. Newer techniques like protons and carbon ions have the intrinsic characteristics maximising the dose on the tumour while minimising the effect on the surrounding healthy tissue, but clinical data are needed for confirmation in randomised phase III trials. Furthermore, it provides an overview of an important discussion issue in PC treatment between urologists and radiation oncologists: the comparison between radical prostatectomy and RT. Current literature reveals that all possible treatment modalities have the same cure rate, but a different toxicity pattern. We recommend proposing the possible different treatment modalities with their own advantages and side-effects to the individual patient. Clinicians and patients should make treatment decisions together (shared decision-making) while using patient decision aids. Ben G. L. Vanneste, Evert J. Van Limbergen, Emile N. van Lin, Joep G. H. van Roermund, and Philippe Lambin Copyright © 2016 Ben G. L. Vanneste et al. All rights reserved. Subureteral Injection with Small-Size Dextranomer/Hyaluronic Acid Copolymer: Is It Really Efficient? Mon, 26 Dec 2016 09:52:15 +0000 The aim of this study was to evaluate the clinical results of patients with vesicoureteral reflux, which were treated with subureteral injection of small-size (80–120 μm) dextranomer/hyaluronic acid copolymer (Dx/HA). Data of 75 children (105 renal units) who underwent STING procedure with small-size Dx/HA for the treatment of vesicoureteral reflux (VUR) in our clinic between 2008 and 2012 were retrospectively analyzed. Preoperative reflux grade and side, injection indication, postoperative urinary infections and urinary symptoms, voiding cystourethrogram, and renal scintigraphy results were evaluated. The success rate of the procedure was 100% in patients with grades 1 and 2 reflux, 91% in patients with grade 3 reflux, and 82.6% in patients with grade 4. Overall success rate of the treated patients was 97%. Endoscopic subureteric injection with Dx/HA procedure has become a reasonable minimally invasive alternative technique to open surgery, long-term antibiotic prophylaxis, and surveillance modalities in treatment of VUR in terms of easy application, low costs and complication rates, and high success rates. Injection material composed of small-size dextranomer microspheres seems superior to normal size Dx/HA, together with offering similar success with low cost. Iyimser Üre, Serhat Gürocak, Özgür Tan, Amirali Farahvash, Cem Senol, Hüseyin Gümüstas, Irfan Atay, and Nuri Deniz Copyright © 2016 Iyimser Üre et al. All rights reserved. Seminal miRNA Relationship with Apoptotic Markers and Oxidative Stress in Infertile Men with Varicocele Mon, 26 Dec 2016 05:42:06 +0000 Aim. This study aimed to assess seminal miRNA relationship with seminal apoptotic markers and oxidative stress (OS) in infertile men associated with varicocele (Vx). Methods. In all, 220 subjects were divided into the following groups: fertile normozoospermic men, fertile normozoospermic men with Vx, infertile oligoasthenoteratozoospermic (OAT) men without Vx, and infertile OAT men with Vx. They were subjected to history taking, clinical examination, and semen analysis. In their semen, the following were estimated: miRNA-122, miRNA-181a, and miRNA-34c5 using quantitative real-time PCR, apoptotic markers (BAX, BCL2) protein expression, and OS markers [malondialdehyde (MDA) and glutathione peroxidase (GPx)]. Results. The mean levels of seminal miRNA-122, miRNA-181a, and miRNA-34c5 were significantly reduced in infertile OAT men with Vx compared with other groups coupled with Vx grade and Vx bilaterality. Seminal miRNA-122, miRNA-181a, and miRNA-34c5 were positively correlated with sperm concentration, total sperm motility, sperm normal morphology, seminal GPx, and seminal BCL2 and negatively correlated with seminal MDA and seminal BAX. Conclusions. Seminal miRNA-122, miRNA-181a, and miRNA-34c5 are decreased in infertile OAT men with Vx associated with increased Vx grade and Vx bilaterality. In addition, they are positively correlated with sperm parameters and negatively correlated with OS, apoptotic markers. Taymour Mostafa, Laila A. Rashed, Nashaat I. Nabil, Ihab Osman, Rashad Mostafa, and Mohamed Farag Copyright © 2016 Taymour Mostafa et al. All rights reserved. Knowledge of the Disease, Perceived Social Support, and Cognitive Appraisals in Women with Urinary Incontinence Wed, 21 Dec 2016 06:52:22 +0000 Social support and knowledge of the disease have been shown to facilitate adaptation to a chronic disease. However, the adaptation process is not fully understood. We hypothesized that these factors can contribute to better adaptation to the disease through their impact on disease-related cognitive appraisal. To analyze the links between social support and the knowledge of the disease, on one hand, and disease-related appraisals, on the other hand, one hundred fifty-eight women with stress UI, aged 32 to 79, took part in the study. Questionnaire measures of knowledge of UI, social support, and disease-related appraisals were used in the study. The level of knowledge correlated significantly negatively with the appraisal of the disease as Harm. The global level of social support correlated significantly positively with three disease-related appraisals: Profit, Challenge, and Value. Four subgroups of patients with different constellations of social support and knowledge of the disease were identified in cluster analysis and were demonstrated to differ significantly on four disease-related appraisals: Profit, Challenge, Harm, and Value. Different cognitive appraisals of UI may be specifically related to social support and knowledge of the disease, with social support affective positive disease-related appraisals, and the knowledge affecting the appraisal of Harm. Katarzyna Szymona-Pałkowska, Konrad Janowski, Agnieszka Pedrycz, Dariusz Mucha, Tadeusz Ambroży, Piotr Siermontowski, Jolanta Adamczuk, Marta Sapalska, Dawid Mucha, and Janusz Kraczkowski Copyright © 2016 Katarzyna Szymona-Pałkowska et al. All rights reserved. Transperitoneal Subcostal Access for Urologic Laparoscopy: Experience of a Large Chinese Center Thu, 15 Dec 2016 07:13:45 +0000 Objective. To present our experience of using transperitoneal subcostal access, Palmer’s point (3 cm below the left costal margin in the midclavicular line), and its right corresponding site, in urologic laparoscopy. Methods. We used Palmer’s point and the right corresponding site for initial access in 302 urologic surgeries (62 cases with prior surgeries). The record of these cases was reviewed. Results. Success rate of initial access is 99.4%, and complication rate of puncturing is only 3.4% with no serious complication. In the cases with prior surgeries, there were only two cases with access complication on the right side (minor laceration of liver). For people with BMI more than 30 kg/m2 (12, 3.9%), the success rate was also 100 percent. Conclusions. Palmer’s point and the corresponding right location are feasible, effective, and safe for initial access in urologic laparoscopic surgeries. This entry technique should be used routinely in urologic laparoscopic surgeries. Lei Zhang, Dong Fang, Xuesong Li, Lin Yao, Gengyan Xiong, Zhisong He, and Liqun Zhou Copyright © 2016 Lei Zhang et al. All rights reserved. Baseline Chronic Kidney Disease and Ischemic Method of Partial Nephrectomy Are Important Factors for the Short- and Long-Term Deterioration in Renal Function for Renal Cell Carcinoma Staged T1-T2: A Retrospective Single Center Study Thu, 15 Dec 2016 06:45:57 +0000 The renal functions of 215 patients (24 with benign renal mass, the rest with RCC staged T1-T2) who underwent partial nephrectomy (PN) between 2003 and 2014 were evaluated to identify predictors of short- and long-term deterioration in renal function after PN among renal cell carcinoma (RCC) patients with or without preoperative predisposition to chronic kidney disease (CKD) and among patients with benign renal mass. The 1- and 5-year predictive factors for de novo CKD were statistically analyzed. The incidence of de novo CKD differed significantly () among patients with benign renal mass, those with RCC but no preoperative CKD predisposition, and those with RCC combined with preoperative CKD predisposition. Independent predictors for de novo CKD at 1 year postoperatively included intraoperative ischemic method, ECOG score, elevated albumin levels, male sex, and smoking exposure (in pack-years). Predictors for de novo CKD at 5 years postoperatively included hypertension, high preoperative albumin levels, De Ritis ratio (aspartate aminotransferase/alanine aminotransferase ratio), smoking exposure, and preoperative predisposition to CKD. Preoperative predisposition to CKD and ischemic method applied during PN, along with other preoperative parameters, were important factors affecting postoperative renal function deterioration in patients with T1-T2 RCC. Sung Han Kim, Jae Young Joung, Ho Kyung Seo, Kang Hyun Lee, and Jinsoo Chung Copyright © 2016 Sung Han Kim et al. All rights reserved. The Influence of Tumor Size on Oncologic Outcomes for Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy Wed, 14 Dec 2016 14:47:54 +0000 Previous studies have reached diverse conclusions about the influence of tumor size on the oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC). In this study, we retrospectively analyzed the records of 687 patients and evaluated how tumor size affected the prognosis of patients with UTUC after surgery. Clinicopathologic characteristics and oncological outcomes were compared according to tumor size (≤3 cm versus >3 cm). During a median follow-up period of 65 months (range 3–144 months), 225 patients (32.8%) died from UTUC and 228 patients (33.2%) experienced intravesical recurrence (IVR). Patients with a larger tumor size tended to have a significantly higher percentage of being male (), tobacco consumption (), lack of preoperative ureteroscopy history (), renal pelvic location (), tumor necrosis (), advanced tumor stage (), higher tumor grade (), and lymph node metastasis (). Univariate analysis revealed that a tumor size >3 cm was significantly associated with worse cancer-specific survival () and IVR (). However, the influence was not statistically significant after controlling for other factors in the multivariate analysis (hazard ratio [HR] 1.124, and HR 1.196, ). In conclusion, UTUC patients with a larger tumor present aggressive biological characteristics and tend to have a worse prognosis. Xiaohong Su, Dong Fang, Xuesong Li, Gengyan Xiong, Lei Zhang, Han Hao, Yanqing Gong, Zheng Zhang, and Liqun Zhou Copyright © 2016 Xiaohong Su et al. All rights reserved. Challenges of Longevity: Safety of Vaginal and Laparoscopic Urogynecological Procedures in Septuagenarians and Older Patients Tue, 13 Dec 2016 09:26:42 +0000 Introduction. Pelvic organ prolapse (POP) and urinary incontinence (UI) have increasing prevalence in the elderly population. The aim of this study was to compare the comorbidities of these procedures between <70 y/o and ≥70 y/o patients. Materials and Methods. In our retrospective study over a period of 2.5 years, 407 patients had received an urogynecological procedure. All patients with POP were treated by reconstructive surgery. Complications were reported using the standardized classification of Clavien-Dindo (CD). The study can be assigned to stage 2b Exploration IDEAL (Idea, Development, Exploration, Assessment, Long-term study)-system of surgical innovation. Results. Operation time, blood loss, and intraoperative complications have not been more frequent in the elderly, whereas hospital stay was significantly longer in ≥70 y/o patients. Regarding postoperative complications, we noticed that ≥70 y/o patients had an almost threefold risk to develop mild early postoperative complications compared to younger patients (OR: 2.86; 95% CI: 1.76–4.66). On the contrary, major complications were not more frequent. No case of life-threatening complication or the need for blood transfusion was reported. Conclusion. After urogynecological procedures, septuagenarians and older patients are more likely to develop mild postoperative complications but not more intraoperative or severe postoperative complications compared to younger patients. R. Joukhadar, A. Wöckel, D. Herr, V. Paulus, J. Radosa, A. Hamza, E. Solomayer, and S. Baum Copyright © 2016 R. Joukhadar et al. All rights reserved. Functional Assessment of the Hautmann Ileal Neobladder with Chimney Modification Using Uroflowmetry and a Questionnaire Tue, 29 Nov 2016 14:29:34 +0000 Urinary diversion reconstruction is essential after radical cystectomy and neobladder reconstruction is accepted as a fine option. This study included 51 patients, who underwent radical cystectomy with orthotopic neobladder reconstruction by a Hautmann ileal neobladder with chimney modification from 2006 to 2014. Functional outcomes were evaluated using a questionnaire and uroflowmetry. Perioperative complications were analyzed retrospectively. The mean follow-up period was 36.1 months. Eighty-six percent of patients voided without clean intermittent catheterization (CIC) assistance. CIC was used 1-2x per day or every time they voided in 8% and 6% of patients, respectively, and 71% of patients were continent. The percentages of patients who used 1, 2, 3-4, and ≥5 pads per day were 15%, 6%, 2%, and 6%, respectively. Daytime and nighttime continence were achieved in 86% and 69% of patients, respectively. Daily mucus leakage was reported in 69% of patients. The mean maximum neobladder capacity, voided volume, postvoid residual volume, and maximum flow rate were 413.2 mL, 370.6 mL, 43.7 mL, and 20.8 mL/s, respectively. Eighteen early and 5 late complications developed in 13 and 5 patients, respectively. Reoperations were needed in 7 patients. The Hautmann ileal neobladder with chimney modification provided satisfactory results regarding functional outcomes. Yong Seong Lee, Ha Bum Jung, Don Kyoung Choi, Sung Tae Cho, Ki Kyung Kim, and Young Goo Lee Copyright © 2016 Yong Seong Lee et al. All rights reserved. Sperm DNA Fragmentation Index and Hyaluronan Binding Ability in Men from Infertile Couples and Men with Testicular Germ Cell Tumor Thu, 24 Nov 2016 14:16:42 +0000 Objective. To investigate sperm DNA fragmentation and sperm functional maturity in men from infertile couples (IC) and men with testicular germ cell tumor (TGCT). Materials and Methods. Semen samples were collected from 312 IC men and 23 men with TGCT before unilateral orchiectomy and oncological treatment. The sperm chromatin dispersion test was performed to determine DNA fragmentation index (DFI) and the ability of sperm to bind with hyaluronan (HA) was assessed. Results. In comparison with the IC men, the men with TGCT had a higher percentage of sperm with fragmented DNA (median 28% versus 21%; ) and a lower percentage of HA-bound sperm (24% versus 66%; ). Normal results of both analyses were observed in 24% of IC men and 4% of men with TGCT. Negative Spearman’s correlations were found between DFI and the percentage of HA-bound sperm in the whole group and in IC subjects and those with TGCT analyzed separately. Conclusions. Approximately 76% of IC men and 96% with TGCT awaiting orchiectomy demonstrated DNA fragmentation and/or sperm immaturity. We therefore recommend sperm banking after unilateral orchiectomy, but before irradiation and chemotherapy; the use of such a deposit appears to be a better strategy to obtain functionally efficient sperms. Katarzyna Marchlewska, Eliza Filipiak, Renata Walczak-Jedrzejowska, Elzbieta Oszukowska, Slawomir Sobkiewicz, Malgorzata Wojt, Jacek Chmiel, Krzysztof Kula, and Jolanta Slowikowska-Hilczer Copyright © 2016 Katarzyna Marchlewska et al. All rights reserved. The Outcome of Repeated Mid Urethral Sling in SUI Treatment after Vaginal Excisions of Primary Failed Sling: Preliminary Study Wed, 23 Nov 2016 06:08:33 +0000 Mid urethral sling is the standard in SUI treatment. Nevertheless, the risk of reoperation reaches 9%. There is no consensus as to the best treatment option for complications. A question is raised: what is the optimal way to achieve the best result in patients after primary failure? The aim of the study was to evaluate the outcomes of repeat MUS surgery in patients after excision of the sling with recurrent SUI. We compared its effectiveness with uncomplicated cases treated with TVT. 27 patients who underwent the repeated MUS and 50 consecutive patients after primary TVT were enrolled in the study. After 6 months, we have found that 24 (88.46%) patients from repeat sling group and 48 (96%) patients after primary sling were dry (1-hour pad test, 2 g or less). The difference between groups was not significant. We showed statistically significant improvement of quality of life in both groups. In conclusion, we showed that repeated sling after MUS excision is almost as effective as primary MUS. We postulate that sling excision and repeated MUS may be the best option for persistent SUI and/or complications after MUS procedures. Further multicenter observations are ongoing as to provide results on bigger group of cases. Jacek Kociszewski, Wojciech Majkusiak, Andrzej Pomian, Paweł Tomasik, Edyta Horosz, Andrzej Kuszka, and Ewa Barcz Copyright © 2016 Jacek Kociszewski et al. All rights reserved. Impact of Training on Three-Dimensional versus Two-Dimensional Laparoscopic Systems on Acquisition of Laparoscopic Skills in Novices: A Prospective Comparative Pilot Study Tue, 22 Nov 2016 13:52:04 +0000 In this prospective educational study, 10 medical students (novices) were randomized to practice two basic laparoscopic tasks from the MISTELS program, namely, Pegboard Transfer (PT) and Intracorporeal Knot Tying (IKT) tasks, using either a 2D or a 3D laparoscopic platform. There was no significant difference between both groups in the baseline assessments (PT task: 130.8 ± 18.7 versus 151.5 ± 33.4; ) (IKT task: 123.9 ± 41.0 versus 122.9 ± 44.9; ). Following two training sessions, there was a significant increase in the scores of PT task for the 2D (130.8 ± 18.7 versus 222.6 ± 7.0; = 0.0004) and the 3D groups (151.5 ± 33.4 versus 211.7 ± 16.2; = 0.0001). Similarly, there was a significant increase in the scores of IKT task for the 2D (123.9 ± 41.0 versus 373.3 ± 47.2; = 0.003) and the 3D groups (122.9 ± 44.9 versus 338.8 ± 28.6; = 0.0005). However, there was no significant difference in the final assessment scores between 2D and 3D groups for both tasks ( > 0.05). Therefore, 3D laparoscopic systems do not provide an advantage over 2D systems for training novices in basic laparoscopic skills. Yasser A. Noureldin, Ana Stoica, Pepa Kaneva, and Sero Andonian Copyright © 2016 Yasser A. Noureldin et al. All rights reserved. Size Does Not Make the Difference: 3D/4D Transperineal Sonographic Measurements of the Female Urethra in the Assessment of Urinary Incontinence Subtypes Mon, 21 Nov 2016 09:29:55 +0000 Purpose. The objective was to evaluate the usefulness of transperineal ultrasound in the assessment of the urethral length and urethral lumen by 3D/4D transperineal sonography to discriminate between female patients with subtypes of urinary incontinence. Methods. A total of 150 female patients underwent an examination because of urinary incontinence. 41 patients were diagnosed with urgency urinary incontinence (OAB), 67 patients were diagnosed with stress urinary incontinence (SUI), and 42 patients were in the control group (CTRL). Three diameters of the urethral lumen (proximal (U1), medial (U2), and distal (U3)) and the urethral length were measured. By the assessment of the urethral lumen, the presence of the urethral funneling was evaluated. Results. We found a significant difference in the urethral length and urethral lumen U2 of OAB and SUI versus CTRL. The urethral length was significantly greater () and the urethral lumen was significantly wider () in the patients with urinary incontinence. The incidence of the urethral funneling was significantly higher () in the study groups with urinary incontinence than in the control group. Conclusions. Our results have shown the urethral changes obtained by ultrasound in patients with urinary incontinence, but they are still insufficient to distinguish between subtypes of urinary incontinence. Tomas Kupec, Ulrich Pecks, Charlotte M. Gräf, Elmar Stickeler, Ivo Meinhold-Heerlein, and Laila Najjari Copyright © 2016 Tomas Kupec et al. All rights reserved. Diagnostic Accuracy of Robot-Guided, Software Based Transperineal MRI/TRUS Fusion Biopsy of the Prostate in a High Risk Population of Previously Biopsy Negative Men Mon, 21 Nov 2016 09:08:11 +0000 Objective. In this study, we compared prostate cancer detection rates between MRI-TRUS fusion targeted and systematic biopsies using a robot-guided, software based transperineal approach. Methods and Patients. 52 patients received a MRIT/TRUS fusion followed by a systematic volume adapted biopsy using the same robot-guided transperineal approach. The primary outcome was the detection rate of clinically significant disease (Gleason grade ≥ 4). Secondary outcomes were detection rate of all cancers, sampling efficiency and utility, and serious adverse event rate. Patients received no antibiotic prophylaxis. Results. From 52 patients, 519 targeted biopsies from 135 lesions and 1561 random biopsies were generated (total ). Overall detection rate of clinically significant PCa was 44.2% (23/52) and 50.0% (26/52) for target and random biopsy, respectively. Sampling efficiency as the median number of cores needed to detect clinically significant prostate cancer was 9 for target (IQR: 6–14.0) and 32 (IQR: 24–32) for random biopsy. The utility as the number of additionally detected clinically significant PCa cases by either strategy was 0% (0/52) for target and 3.9% (2/52) for random biopsy. Conclusions. MRI/TRUS fusion based target biopsy did not show an advantage in the overall detection rate of clinically significant prostate cancer. Malte Kroenig, Kathrin Schaal, Matthias Benndorf, Martin Soschynski, Philipp Lenz, Tobias Krauss, Vanessa Drendel, Gian Kayser, Philipp Kurz, Martin Werner, Ulrich Wetterauer, Wolfgang Schultze-Seemann, Mathias Langer, and Cordula A. Jilg Copyright © 2016 Malte Kroenig et al. All rights reserved. ZFP91: A Noncanonical NF-κB Signaling Pathway Regulator with Oncogenic Properties Is Overexpressed in Prostate Cancer Wed, 16 Nov 2016 09:56:25 +0000 Novel molecular targets are being searched to aid in prostate cancer diagnosis and therapy. Recently, ZFP91 zinc finger protein has been found to be upregulated in prostate cancer cell lines. It is a potentially important oncogenic protein; however only limited data regarding its biological function and expression patterns are available. To date, ZFP91 has been shown to be a key factor in activation of noncanonical NF-B signaling pathway as well as to be involved in HIF-1α signaling in cancer cells. The present study aimed to characterize ZFP91 expression in prostate cancer specimens. Furthermore, since our earlier reports showed discrepancies between ZFP91 mRNA and protein levels, we studied this interrelationship in LNCaP and PC-3 prostate cancer cell lines using siRNA mediated knockdown. QPCR analysis revealed marked upregulation of ZFP91 mRNA in the majority of prostate cancer specimens. Transfection of prostate cancer cells with ZFP91 siRNA resulted in a 10-fold decrease in mRNA levels. On a protein level, however, no inhibitory effect was observed over the time of the cell culture. We conclude that ZFP91 is overexpressed in prostate cancer and that potential accumulation of the ZFP91 protein in studied cells may be of importance in prostate cancer biology. Lukasz Paschke, Karol Jopek, Marta Szyszka, Marianna Tyczewska, Agnieszka Ziolkowska, Marcin Rucinski, and Ludwik K. Malendowicz Copyright © 2016 Lukasz Paschke et al. All rights reserved. Prediction of Bacillus Calmette-Guerin Response in Patients with Bladder Cancer after Transurethral Resection of Bladder Tumor by Using Genetic Variation Based on Genomic Studies Tue, 08 Nov 2016 13:50:26 +0000 Purpose. We aimed to comprehensively review contemporary literature on genetic and epigenetic biomarkers associated with the prediction of Bacillus Calmette-Guerin (BCG) response after the transurethral resection of a bladder tumor and to discuss the application of these biomarkers in precision cancer care for bladder cancer. Method. We performed a systematic review of published literatures in the databases PubMed and Embase by using the following key words: bladder cancer, BCG, gene, and methylation. Studies associated with cell lines, animal models, and muscle invasive bladder cancer were excluded. Results. The genetic variations associated with BCG response can be classified into three categories: germline variations, somatic variations, and epigenetic alterations. Genes related to BCG response were mainly involved in single-nucleotide polymorphisms, copy number variations, and gene methylations. Conclusions. Although these gene alterations are currently the most promising predictive markers of BCG response, most studies about bladder cancer DNA biomarkers are related to germline variations in candidate genes, and the results are not consistent. Only one study is related to somatic variation, and further evaluation in large-scale validation studies should be conducted to assess the potential clinical application of these findings. In addition, other biomarkers based on different “–omics” technologies should be considered in future studies. Ning Zhang, Guangliang Jiang, Xu Liu, Rong Na, Xiang Wang, and Jianfeng Xu Copyright © 2016 Ning Zhang et al. All rights reserved. Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in Nonmetastatic Renal Cell Carcinoma: A Large, Multicenter Cohort Analysis Sun, 06 Nov 2016 06:39:36 +0000 Background. The prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) in nonmetastatic renal cell carcinoma (non-mRCC) is controversial, although NLR has been established as a prognostic factor in several cancers. The objective of our study was to assess the prognostic significance of preoperative NLR in non-mRCC, based on a large, multicenter cohort analysis. Methods. Totally, 1,284 non-mRCC patients undergoing surgery were enrolled from six institutions between 2000 and 2014. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were calculated, and the prognostic significance of NLR was evaluated. Results. Patients with higher NLR had larger tumors (), higher T stage (), worse Eastern Cooperative Oncology Group performance status (), worse symptoms (), sarcomatoid differentiation (), and tumor necrosis (). The 5-year RFS and CSS rates were significantly lower in patients with high NLR than in those with low NLR (each ). Multivariate analysis identified NLR to be an independent predictor of RFS and CSS (each ). Moreover, predictive accuracy of multivariate models for RFS and CSS increased by 2.2% and 4.2%, respectively, with NLR inclusion. Conclusions. Higher NLR was associated with worse clinical behavior of non-mRCC. Also, NLR was a significant prognostic factor of both RFS and CSS. Seok-Soo Byun, Eu Chang Hwang, Seok Ho Kang, Sung-Hoo Hong, Jinsoo Chung, Tae Gyun Kwon, Hyeon Hoe Kim, Cheol Kwak, Yong-June Kim, and Won Ki Lee Copyright © 2016 Seok-Soo Byun et al. All rights reserved. Diet, Lifestyles, Family History, and Prostate Cancer Incidence in an East Algerian Patient Group Wed, 19 Oct 2016 09:35:38 +0000 Prostate cancer (PC) is the fourth most common cancer in men and the sixth leading cause of death in Algeria. To examine the relationship between lifestyle factors, including diet, and family history and PC risk, a case-control study was performed in an eastern Algerian population, comprising 90 patients with histologically confirmed PC and 190 controls. Data collection was carried out through a structured questionnaire and statistical analysis was performed to evaluate the different variables. The data showed that consumption of lamb and beef meat and high intake of animal fat and dairy products increased PC risk. Seven to thirteen vegetables servings per week and fourteen or more servings decreased PC risk by 62% and 96%, respectively. Seven to fourteen fruit servings per week decrease PC risk by 98%. Green tea consumption reduced the risk of PC but the results were statistically borderline. Increased risk was observed for individuals with family history of PC in first and in second degree. A positive strong association was also found for alcohol and smoking intake and a dose-response relationship existed for quantity and history of smoking. This study suggests that dietary habits, lifestyle factors, and family history have influence on the development of PC in Algerian population. Somia Lassed, Cláudia M. Deus, Nuno Lourenço, Abderrezak Dahdouh, Albert A. Rizvanov, Paulo J. Oliveira, and Djamila Zama Copyright © 2016 Somia Lassed et al. All rights reserved. Comparison of Perineal Sonographically Measured and Functional Urodynamic Urethral Length in Female Urinary Incontinence Thu, 13 Oct 2016 07:57:37 +0000 Objectives. To detect the anatomical insufficiency of the urethra and to propose perineal ultrasound as a useful, noninvasive tool for the evaluation of incontinence, we compared the anatomical length of the urethra with the urodynamic functional urethral length. We also compared the urethral length between continent and incontinent females. Methods. 149 female patients were enrolled and divided into four groups (stress, urge, or mixed incontinence; control). Sonographically measured urethral length (SUL) and urodynamic functional urethral length (FUL) were analyzed statistically. Standardized and internationally validated incontinence questionnaire ICIQ-SF results were compared between each patient group. Results. Perineal SUL was significantly longer in incontinent compared to continent patients (). Pairwise comparison of each incontinent type (stress, urge, or mixed incontinence) with the control group showed also a significant difference (). FUL was significantly shorter in incontinent patients than in the control group (). But pairwise comparison showed only a significant difference for the stress incontinence group compared with the control group () and not for the urge or mixed incontinent group. No clear correlation between SUL, FUL, and ICIQ-SF score was found. Conclusions. SUL measured by noninvasive perineal ultrasound is a suitable parameter in the assessment of female incontinence, since incontinent women show a significantly elongated urethra as a sign of tissue insufficiency, independent of the type of incontinence. Laila Najjari, Nadine Janetzki, Lieven Kennes, Elmar Stickeler, Julia Serno, and Julia Behrendt Copyright © 2016 Laila Najjari et al. All rights reserved. Expansion of Submucosal Bladder Wall Tissue In Vitro and In Vivo Thu, 29 Sep 2016 05:44:33 +0000 In order to develop autologous tissue engineering of the whole wall in the urinary excretory system, we studied the regenerative capacity of the muscular bladder wall. Smooth muscle cell expansion on minced detrusor muscle in vitro and in vivo with or without urothelial tissue was studied. Porcine minced detrusor muscle and urothelium were cultured in vitro under standard culture conditions for evaluation of the explant technique and in collagen for tissue sectioning and histology. Autografts of minced detrusor muscle with or without minced urothelium were expanded on 3D cylinder moulds by grafting into the subcutaneous fat of the pig abdominal wall. Moulds without autografts were used as controls. Tissue harvesting, mincing, and transplantation were performed as a one-step procedure. Cells from minced detrusor muscle specimens migrated and expanded in vitro on culture plastic and in collagen. In vivo studies with minced detrusor autografts demonstrated expansion and regeneration in all specimens. Minced urothelium autografts showed multilayered transitional urothelium when transplanted alone but not in cotransplantation with detrusor muscle; thus, minced bladder mucosa was not favored by cografting with minced detrusor. No regeneration of smooth muscle or epithelium was seen in controls. Gisela Reinfeldt Engberg, Clara Ibel Chamorro, Agneta Nordenskjöld, and Magdalena Fossum Copyright © 2016 Gisela Reinfeldt Engberg et al. All rights reserved. Retrograde versus Antegrade Approach for the Management of Large Proximal Ureteral Stones Tue, 27 Sep 2016 14:14:41 +0000 Objective. To evaluate and compare the efficacy and safety of retrograde versus antegrade ureteroscopic lithotripsy for the treatment of large proximal ureteral stones. Patients and Methods. We retrospectively analyzed the medical records of patients with proximal ureteral stones >15 mm, treated in our institution from January 2011 to January 2016. Intraoperative parameters, postoperative outcomes, and complications were recorded and compared between the two techniques. Results. Our analysis included 57 patients. Thirty-four patients (59.6%) underwent retrograde and 23 patients (40.4%) underwent antegrade ureteroscopy. There was no significant difference in patients’ demographics and stone characteristics between the groups. Stone-free rate was significantly higher () in the antegrade group (100%) compared to retrograde one (82.4%). Fluoroscopy time, procedure duration, and length of hospitalization were significantly () lower in retrograde approach. On the other hand, the need for postoperative stenting was significantly lower in the antegrade group (). No difference was found between the groups () regarding postoperative complications. Conclusions. Antegrade ureteroscopy is an efficient and safe option for the management of large proximal ureteral stones. It may achieve high stone-free rates compared to retrograde ureteroscopy with the drawback of longer operative time, fluoroscopy time, and length of hospitalization. Stavros Sfoungaristos, Ioannis Mykoniatis, Ayman Isid, Ofer N. Gofrit, Shilo Rosenberg, Guy Hidas, Ezekiel H. Landau, Dov Pode, and Mordechai Duvdevani Copyright © 2016 Stavros Sfoungaristos et al. All rights reserved. Isolated Male Epispadias: Anatomic Functional Restoration Is the Primary Goal Sun, 18 Sep 2016 13:05:00 +0000 Background. Isolated male epispadias (IME) is a rare congenital penile malformation, as often part of bladder-exstrophy-epispadias complex (BEEC). In its isolated presentation, it consists in a defect of the dorsal aspect of the penis, leaving the urethral plate open. Occurrence of urinary incontinence is related to the degree of dorsal displacement of the meatus and the underlying underdevelopment of the urethral sphincter. The technique for primary IME reconstruction, based on anatomic restoration of the urethra and bladder neck, is here illustrated. Patients and Methods. A retrospective database was created with patients who underwent primary IME repair between June 1998 and February 2014. Intraoperative variables, postoperative complications, and outcomes were assessed. A descriptive statistical analysis was performed. Results and Limitations. Eight patients underwent primary repair, with penopubic epispadias (PPE) in 3, penile epispadias (PE) in 2, and glandular epispadias (GE) in 3. Median age at surgery was 13.0 months [–47]; median follow-up was 52 months [–120]. Complications requiring further surgery were reported in two patients, while further esthetic surgeries were required in 4 patients. Conclusion. Anatomical restoration in primary IME is safe and effective, with acceptable results given the initial pathology. Anne-Francoise Spinoit, Tom Claeys, Elke Bruneel, Achilles Ploumidis, Erik Van Laecke, and Piet Hoebeke Copyright © 2016 Anne-Francoise Spinoit et al. All rights reserved. Pretreatment Neutrophil-to-Lymphocyte Ratio Can Predict the Prognosis in Bladder Cancer Patients Who Receive Gemcitabine and Nedaplatin Therapy Thu, 08 Sep 2016 08:11:36 +0000 Introduction and Objectives. Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a simple marker of the systemic inflammatory response in critical care patients. We previously assessed the utility of NLR as a biomarker to predict tumor recurrence and cancer death in bladder cancer patients who underwent radical cystectomy. In this study, we evaluated the prognostic impact of NLR in bladder cancer patients who received gemcitabine and nedaplatin (GN) chemotherapy. Methods. A total of 23 patients who received GN chemotherapy for advanced bladder cancer were enrolled in this study. The cut-off point of NLR according to the sensitivity and specificity levels was derived from the area under receiver operator characteristics (AUROC) curve plotted for disease progression or overall mortality. Results. The NLR cut-off point was determined as 4.14 for both tumor progression and overall mortality. Median progression-free survival (PFS)/overall survival (OS) in the higher NLR group (NLR ≥ 4.14) and lower NLR group (NLR < 4.14) were 194/468 days versus 73/237 days, respectively. Kaplan-Meier analysis showed that higher NLR significantly correlated with poorer PFS () and OS (). Conclusions. NLR may serve as a new biomarker to predict responses to GN-based chemotherapy in advanced bladder cancer patients and/or their prognosis. Shinji Ohtake, Takashi Kawahara, Ryo Kasahara, Hiroki Ito, Kimito Osaka, Yusuke Hattori, Jun-ichi Teranishi, Kazuhide Makiyama, Nobuhiko Mizuno, Susumu Umemoto, Yasuhide Miyoshi, Noboru Nakaigawa, Hiroshi Miyamoto, Masahiro Yao, and Hiroji Uemura Copyright © 2016 Shinji Ohtake et al. All rights reserved. Efficacy of Immediate Switching from Bicalutamide to Flutamide as Second-Line Combined Androgen Blockade Thu, 14 Jul 2016 06:24:19 +0000 We determined whether prostate specific antigen (PSA) would decrease with immediate antiandrogen switching from bicalutamide (BCL) to flutamide (FLT) in patients receiving combined androgen blockade for advanced prostate cancer. From 2002 to 2006, 20 patients who showed PSA failure after first-line hormonal therapy with a luteinizing hormone-release hormone (LH-RH) agonist and BCL were enrolled. All patients were immediately switched from BCL to FLT, administered with an LH-RH agonist, as second-line combined androgen blockade (CAB). We evaluated the PSA response to second-line CAB. Eight patients (40%) were responsive, showing PSA decreases of at least 50%. The median (range) duration of the PSA response was 18.4 (3–26) months. Second-line CAB using FLT was effective in 40% of patients who received first-line CAB using BCL. The lower Gleason scores at the initial prostate biopsy probably reflect the response to second-line CAB. Responders showed significantly better OS and CSS in the determination of any PSA decline and 40% PSA decline. The median OS duration in nonresponders and responders (40% PSA decline) was 1433 days versus 3617 days. It is concluded that an immediate switch from BCL to FLT is effective for some CRPC patients after first-line CAB using BCL. Yumiko Yokomizo, Takashi Kawahara, Yasuhide Miyoshi, Masako Otani, Shoji Yamanaka, Jun-ichi Teranishi, Kazumi Noguchi, Masahiro Yao, and Hiroji Uemura Copyright © 2016 Yumiko Yokomizo et al. All rights reserved. Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy Wed, 20 Apr 2016 07:07:23 +0000 Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (), pathological T stage (), lymph node metastasis (), or resection margin status (). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy. Yoko Maeda, Takashi Kawahara, Mitsuyuki Koizumi, Hiroki Ito, Yohei Kumano, Mari Ohtaka, Takuya Kondo, Taku Mochizuki, Yusuke Hattori, Jun-ichi Teranishi, Yasushi Yumura, Yasuhide Miyoshi, Masahiro Yao, Hiroshi Miyamoto, and Hiroji Uemura Copyright © 2016 Yoko Maeda et al. All rights reserved. Efficacy and Safety of Silodosin and Dutasteride Combination Therapy in Acute Urinary Retention due to Benign Prostatic Hyperplasia: A Single-Arm Prospective Study Mon, 18 Apr 2016 07:07:55 +0000 This study aimed to assess the efficacy of combination therapy with dutasteride and silodosin in patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH). Eighty consecutive patients with a first episode of AUR were enrolled in this study. All patients received silodosin 8 mg and dutasteride 0.5 mg daily. Trial without catheter (TWOC) was attempted every 2 weeks until 12 weeks after the initiation of medication. The primary endpoint was the rate of catheter-free status at 12 weeks. Voided volume (VV), postvoid residual urine (PVR), uroflowmetry, International Prostatic Symptoms Score (IPSS), and quality of life due to urinary symptoms (IPSS-QOL) were also measured. All patients were followed up for more than 12 weeks and were included in this analysis. The success rate of TWOC at 12 weeks was 88.8%. VV and maximum urinary flow rate were significantly higher at 2, 4, 8, and 12 weeks compared with the time of AUR (). IPSS and IPSS-QOL were significantly lower at 2, 4, 8, and 12 weeks compared with the time of AUR (). In conclusion, a combination of dutasteride and silodosin therapy may be effective and safe for patients with AUR due to BPH. Kazuhisa Hagiwara, Takuya Koie, Hiromichi Iwamura, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, and Chikara Ohyama Copyright © 2016 Kazuhisa Hagiwara et al. All rights reserved. Microelectrical Impedance Spectroscopy for the Differentiation between Normal and Cancerous Human Urothelial Cell Lines: Real-Time Electrical Impedance Measurement at an Optimal Frequency Sun, 21 Feb 2016 13:47:21 +0000 Purpose. To distinguish between normal (SV-HUC-1) and cancerous (TCCSUP) human urothelial cell lines using microelectrical impedance spectroscopy (μEIS). Materials and Methods. Two types of μEIS devices were designed and used in combination to measure the impedance of SV-HUC-1 and TCCSUP cells flowing through the channels of the devices. The first device (μEIS-OF) was designed to determine the optimal frequency at which the impedance of two cell lines is most distinguishable. The μEIS-OF trapped the flowing cells and measured their impedance at a frequency ranging from 5 kHz to 1 MHz. The second device (μEIS-RT) was designed for real-time impedance measurement of the cells at the optimal frequency. The impedance was measured instantaneously as the cells passed the sensing electrodes of μEIS-RT. Results. The optimal frequency, which maximized the average difference of the amplitude and phase angle between the two cell lines (), was determined to be 119 kHz. The real-time impedance of the cell lines was measured at 119 kHz; the two cell lines differed significantly in terms of amplitude and phase angle (). Conclusion. The μEIS-RT can discriminate SV-HUC-1 and TCCSUP cells by measuring the impedance at the optimal frequency determined by the μEIS-OF. Yangkyu Park, Hyeon Woo Kim, Joho Yun, Seungwan Seo, Chang-Ju Park, Jeong Zoo Lee, and Jong-Hyun Lee Copyright © 2016 Yangkyu Park et al. All rights reserved. Prognosis Risk of Urosepsis in Critical Care Medicine: A Prospective Observational Study Wed, 03 Feb 2016 10:23:55 +0000 This study aimed to investigate the clinical features of urosepsis and to raise awareness of this problem. Of the 112 sepsis patients enrolled, 36 were identified as having urosepsis. The bacteria involved in the infection leading to urosepsis included Escherichia coli, Proteus species, Enterococcus species, Klebsiella species, other Gram-positive cocci, and Pseudomonas aeruginosa. Although the organ/system dysfunction appeared earlier in the urosepsis patients than in the other sepsis patients ( versus hours, ), the urosepsis patients presented with a better prognosis and lower 28-day mortality rate than the others (6% versus 37%). In the multivariate analysis, the type of sepsis (urosepsis, OR = 0.019, 95% CI = 0.001, 0.335, ) and SOFA score (OR = 1.896, 95% CI = 1.012, 3.554, ) remained significantly associated with the survival. The time of admission to the intensive care unit of 17 patients transferred from the Department of Urinary Surgery was significantly prolonged compared with those transferred from other departments ( versus hours, ). In conclusion, urosepsis suggested a better prognosis, but attention needs to be paid in clinical practice, especially in urinary surgery. Xin-Hua Qiang, Tie-Ou Yu, Yi-Nan Li, and Li-Xin Zhou Copyright © 2016 Xin-Hua Qiang et al. All rights reserved. Male Infertility: Genetics, Mechanism, and Therapies Sun, 31 Jan 2016 08:21:01 +0000 Charles Coutton, Rafael A. Fissore, Gianpiero D. Palermo, Katrien Stouffs, and Aminata Touré Copyright © 2016 Charles Coutton et al. All rights reserved. An Update on Oxidative Damage to Spermatozoa and Oocytes Thu, 28 Jan 2016 15:04:37 +0000 On the one hand, reactive oxygen species (ROS) are mandatory mediators for essential cellular functions including the function of germ cells (oocytes and spermatozoa) and thereby the fertilization process. However, the exposure of these cells to excessive levels of oxidative stress by too high levels of ROS or too low levels of antioxidative protection will render these cells dysfunctional thereby failing the fertilization process and causing couples to be infertile. Numerous causes are responsible for the delicate bodily redox system being out of balance and causing disease and infertility. Many of these causes are modifiable such as lifestyle factors like obesity, poor nutrition, heat stress, smoking, or alcohol abuse. Possible correctable measures include foremost lifestyle changes, but also supplementation with antioxidants to scavenge excessive ROS. However, this should only be done after careful examination of the patient and establishment of the individual bodily antioxidant needs. In addition, other corrective measures include sperm separation for assisted reproductive techniques. However, these techniques have to be carried out very carefully as they, if applied wrongly, bear risks of generating ROS damaging the germ cells and preventing fertilization. Chinyerum S. Opuwari and Ralf R. Henkel Copyright © 2016 Chinyerum S. Opuwari and Ralf R. Henkel. All rights reserved. Do We Pay Enough Attention to Culture Conditions in Context of Perinatal Outcome after In Vitro Fertilization? Up-to-Date Literature Review Thu, 28 Jan 2016 11:15:56 +0000 Adverse perinatal outcomes in singleton IVF pregnancies have been most often explained by parental underlying diseases and so far laboratory conditions during embryo culture are still not explored well. The following review discusses the current state of knowledge on the influence of IVF laboratory procedures on the possible perinatal outcome. The role of improved media for human embryo culture is unquestionable. Addition of certain components to culture media and their effect on embryo survival and implantation rates have been taken into consideration recently and studied on animal model. Impact of media on perinatal outcome in IVF offspring has also been studied. It has been discovered that epigenetic changes and neonatal birth weight are probably associated with the use of specific culture media, as is the relation between placental size and its influence on perinatal outcome. There are still questions in the discussion about duration of embryo culture (cleavage stage versus blastocyst transfer). Some of the IVF methods, such as in vitro maturation of oocytes and freezing/thawing procedures, also require well-powered randomized controlled trials in order to define their exact impact on perinatal outcome. Constant further research is needed to assess the impact of laboratory environment on fetal and postnatal development. Piotr Marianowski, Filip A. Dąbrowski, Aleksandra Zyguła, Mirosław Wielgoś, and Iwona Szymusik Copyright © 2016 Piotr Marianowski et al. All rights reserved. The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis Thu, 28 Jan 2016 11:12:02 +0000 Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential. Danilo Cimadomo, Antonio Capalbo, Filippo Maria Ubaldi, Catello Scarica, Antonio Palagiano, Rita Canipari, and Laura Rienzi Copyright © 2016 Danilo Cimadomo et al. All rights reserved. Sertoli Cell-Only Syndrome: Behind the Genetic Scenes Tue, 26 Jan 2016 07:07:06 +0000 Sertoli cell-only syndrome is defined by the complete absence of germ cells in testicular tissues and always results in male infertility. The aetiology often remains unknown. In this paper, we have investigated possible causes of Sertoli cell-only syndrome with a special focus on genetic causes. Our results show that, for a large part of the patients (>23% in an unselected group), the sex chromosomes are involved. The majority of patients had a Klinefelter syndrome, followed by patients with Yq microdeletions. Array comparative genomic hybridization in a selected group of “idiopathic patients” showed no known infertility related copy number variations. Katrien Stouffs, Alexander Gheldof, Herman Tournaye, Deborah Vandermaelen, Maryse Bonduelle, Willy Lissens, and Sara Seneca Copyright © 2016 Katrien Stouffs et al. All rights reserved. Acupuncture for Erectile Dysfunction: A Systematic Review Sun, 17 Jan 2016 13:52:09 +0000 Background. Acupuncture is increasingly used to treat patients with erectile dysfunction (ED), and our systematic review aimed to evaluate the current evidence for the efficacy and safety of acupuncture in treating ED. Methods. An electronic search was conducted in eight databases to identify randomized controlled trials (RCTs) of acupuncture for treating erectile dysfunction that were published in English and Chinese. The Cochrane Risk of Bias tool was used to assess the risk of bias. Results. Three RCTs with a total of 183 participants met the inclusion criteria. One trial showed the beneficial effects of acupuncture compared with sham acupuncture while the others did not. One trial suggested that acupuncture combined with psychological therapy was superior to psychological therapy alone. However, the overall methodological and reporting quality of the studies was low. The safety of acupuncture for ED was unclear because there were too few reports on this topic. Conclusion. The available evidence supporting that acupuncture alone improves ED was insufficient and the available studies failed to show the specific therapeutic effect of acupuncture. Future well-designed and rigorous RCTs with a large sample size are required. This trial is registered with CRD42014013575. Xiaoming Cui, Jing Zhou, Zongshi Qin, and Zhishun Liu Copyright © 2016 Xiaoming Cui et al. All rights reserved. The Impact of Sperm Metabolism during In Vitro Storage: The Stallion as a Model Tue, 12 Jan 2016 11:42:09 +0000 In vitro sperm storage is a necessary part of many artificial insemination or in vitro fertilization regimes for many species, including the human and the horse. In many situations spermatozoa are chilled to temperatures between 4 and 10°C for the purpose of restricting the metabolic rate during storage, in turn, reducing the depletion of ATP and the production of detrimental by-products such as reactive oxygen species (ROS). Another result of lowering the temperature is that spermatozoa may be “cold shocked” due to lipid membrane phase separation, resulting in reduced fertility. To overcome this, a method of sperm storage must be developed that will preclude the need to chill spermatozoa. If a thermally induced restriction-of-metabolic-rate strategy is not employed, ATP production must be supported while ameliorating the deleterious effects of ROS. To achieve this end, an understanding of the nature of energy production by the spermatozoa of the species of interest is essential. Human spermatozoa depend predominantly on glycolytic ATP production, producing significantly less ROS than oxidative phosphorylation, with the more efficient pathway predominantly employed by stallion spermatozoa. This review provides an overview of the implications of sperm metabolism for in vitro sperm storage, with a focus on ambient temperature storage in the stallion. Zamira Gibb and Robert J. Aitken Copyright © 2016 Zamira Gibb and Robert J. Aitken. All rights reserved. Outcomes of Intracytoplasmic Sperm Injection Cycles for Complete Teratozoospermia: A Case-Control Study Using Paired Sibling Oocytes Tue, 29 Dec 2015 14:03:48 +0000 Objective. To investigate the outcomes of intracytoplasmic sperm injection (ICSI) cycles where sibling oocytes from a single donor were split between two recipients based on strict sperm morphology. Methods. Retrospective cohort study. All ICSI cycles had one donor’s oocytes split between two recipients in a 1 : 1 ratio based on strict sperm morphology, that is, one male partner had morphology of 0% and the other had morphology of >1%. Fertilization, positive hCG, clinical pregnancy, spontaneous miscarriage, and live birth rates of the aforementioned groups were compared. Results. The baseline characteristics of the two groups (), including semen parameters of the male partners, were comparable. There was no difference in the fertilization rates when comparing the 0% group to the >1% group (78.7% versus 81.6%; ). The overall positive hCG, clinical pregnancy, spontaneous miscarriage, and live birth rates for the 0% group were 61.2%, 49.5%, 10.7%, and 38.8%, respectively. The corresponding rates in the >1% group were positive hCG (63.1%), clinical pregnancy (55.3%), spontaneous miscarriage (7.77%), and live birth (46.6%). Conclusions. The fertilization and pregnancy outcomes of ICSI cycles for strict sperm morphology of 0% versus morphology of >1% are equivalent. These results can provide reassurance to couples undergoing ICSI for severe teratospermia. Nigel Pereira, Queenie V. Neri, Jovana P. Lekovich, Steven D. Spandorfer, Gianpiero D. Palermo, and Zev Rosenwaks Copyright © 2015 Nigel Pereira et al. All rights reserved. Variations in Antioxidant Genes and Male Infertility Thu, 05 Nov 2015 09:58:42 +0000 Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted. Bolan Yu and Zhaofeng Huang Copyright © 2015 Bolan Yu and Zhaofeng Huang. All rights reserved. Varicocele Repair Improves Testicular Histology in Men with Nonobstructive Azoospermia Tue, 27 Oct 2015 07:49:06 +0000 Objective. To determine the histopathological differences after varicocele repair in testicular tissue in males with nonobstructive azoospermia. Methods. Between 2009 and 2014, 45 men with complete azoospermia and palpable varicocele, presenting with primary infertility of at least 1 year, undergoing varicocele repair at our institution were selected for the study. A standard systematic testicular 6-core Tru-Cut biopsy was performed during varicocele repair. Other biopsies were obtained from each testicle of all patients at the time of microscopic sperm extraction procedure. Results. Nineteen patients were selected for the study. Testicular biopsy specimens were classified as Sertoli cell only on preoperative histopathological analysis in 14 patients. After varicocele repair, focal spermatogenesis and late maturation arrest were found in these patients. Average Johnsen score was significantly increased after varicocelectomy . Motile sperm was found in one patient on postoperative semen analyses and in 10 more patients in the microscopic sperm extraction procedure. Preoperative high serum follicle stimulating hormone level and venous reflux were significantly and negatively correlated with the increase in average Johnsen score . Conclusions. Our findings suggest significant improvement in testicular histology after varicocele repair. Murat Ustuner, Hasan Yilmaz, Ufuk Yavuz, Seyfettin Ciftci, Ali Saribacak, Bahri Serkan Aynur, Hikmet Yasar, and Mustafa Melih Culha Copyright © 2015 Murat Ustuner et al. All rights reserved. Prevalence and Risk Factors of Prostate Cancer in Chinese Men with PSA 4–10 ng/mL Who Underwent TRUS-Guided Prostate Biopsy: The Utilization of PAMD Score Sun, 18 Oct 2015 12:13:12 +0000 Purpose. To elucidate the characteristics and risk factors for positive biopsy outcomes in Chinese patients with prostate specific antigen (PSA) 4–10 ng/mL and develop a risk-stratification score model. Methods. The data of 345 patients who underwent transrectal ultrasound-guided prostate biopsy between 2011 and 2013 was retrospectively analyzed. Digital rectal examination (DRE), prostate volume (PV), magnetic resonance imaging (MRI), and smoking status were also collected. Positive biopsy outcomes were defined as prostate cancer (PCa) and high grade PCa (HGPCa, Gleason ). Results. The median PSA was 7.15 (IQR 5.91–8.45) ng/mL. Overall 138 patients (40.0%) were shown to have PCa, including 100 patients (29.0%) with HGPCa. Smaller PV, elder age, MRI results, and positive DRE were proved to be predictive factors for positive biopsy outcomes in both univariate and multivariate analysis. We developed a “PAMD” score which combined the four factors to categorize patients into three risk groups, and the model performed good predictive sensitivity and specificity. Conclusion. The prevalence of prostate cancer in Chinese patients with PSA 4–10 ng/mL was 40%, including 29% patients with high grade disease. DRE, age, MRI, and PV were predictive factors for positive biopsy outcomes, and the PAMD score model could be utilized for risk-stratification and decision-making. Dong Fang, Da Ren, Chenglin Zhao, Xuesong Li, Wei Yu, Rui Wang, Huihui Wang, Chenguang Xi, Qun He, Xiaoying Wang, Zhongcheng Xin, and Liqun Zhou Copyright © 2015 Dong Fang et al. All rights reserved. Open Partial Nephrectomy for High-Risk Renal Masses Is Associated with Renal Pseudoaneurysms: Assessment of a Severe Procedure-Related Complication Sun, 11 Oct 2015 14:09:27 +0000 Objectives. A symptomatic renal pseudoaneurysm (RPA) is a severe complication after open partial nephrectomy (OPN). The aim of our study was to assess incidence and risk factors for RPA formation. Furthermore, we present our management strategy. Patients and Methods. Clinical records of consecutive patients undergoing OPN were assessed for surgical outcome and postoperative complications. Renal masses were risk stratified for tumor complexity according to the PADUA score. Uni- and multivariate analysis for symptomatic RPAs were performed using the -tests and logistic regression. Results. We identified 233 patients treated with OPN. Symptomatic RPAs were observed in 13 (5.6%) patients, on average 14 (4–42) days after surgery. Uni- and multivariate analysis identified tumor complexity to be an independent predictor for symptomatic RPAs (). There was a significant correlation between RPAs and transfusion and the duration of stay ( and ). Symptomatic RPAs were diagnosed with CT scans and successfully treated with arterial embolization. Discussion. Symptomatic RPAs are not uncommon after OPN for high-risk renal masses. A high nephrometry score is a predictor for this severe complication and may enable a risk-stratified followup. RPAs can successfully be located by CT angiography, which enables targeted angiographic treatment. M. C. Kriegmair, P. Mandel, N. Rathmann, S. J. Diehl, D. Pfalzgraf, and M. Ritter Copyright © 2015 M. C. Kriegmair et al. All rights reserved. Cancer Characteristics and Current Treatments of Patients with Renal Cell Carcinoma in Sweden Sun, 11 Oct 2015 13:49:00 +0000 Methodology. Since the start in 2005 virtually all patients with newly diagnosed renal cell carcinoma (RCC) in Sweden are reported to the National Swedish Kidney Cancer Register (NSKCR). The register contains information on histopathology, nuclear grade, clinical stage, preoperative work-up, treatment, recurrence, and survival. Results. A total of 8556 patients with newly diagnosed RCC were registered in the NSKCR from 2005 to 2013 resulting in a coverage of 99% as compared to the Swedish Cancer Registry. The mean tumor size at detection decreased from 70 mm in 2005 to 64 mm in 2010. The proportion of patients who were incidentally detected increased. The proportion of patients with tumor stage T1a who underwent partial nephrectomy increased from 22% in 2005 to 56% in 2012. Similarly, the proportion of laparoscopically performed radical nephrectomies increased from 6% in 2005 to 17% in 2010. During the five years of follow-up 20% of the patients had a recurrence. Conclusion. Over the last decade there has been a trend of earlier detection and less advanced tumors at detection in patients with RCC. An increasing proportion of the patients undergo laparoscopic and nephron-sparing procedures. Andreas Thorstenson, Ulrika Harmenberg, Per Lindblad, Benny Holmström, Sven Lundstam, and Börje Ljungberg Copyright © 2015 Andreas Thorstenson et al. All rights reserved. Robot-Assisted Laparoscopic Nephroureterectomy versus Hand-Assisted Laparoscopic Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: A Matched Comparison Study Sun, 11 Oct 2015 13:45:31 +0000 Objectives. To investigate the perioperative and oncological outcomes of hand-assisted laparoscopic nephroureterectomy (HANU) and robotic-assisted nephroureterectomy (RANU). Methods. Patients who underwent RANU were matched by sex, age (±5 years), and tumor location to those who underwent HANU; 18 matched pairs were included. Results. Each group consisted of five men and 13 women. The mean age was 70.4 years in RANU group and 69.6 years in HANU group (). Each group contained 10 patients with tumor location in the renal pelvis, five in the ureter, and three in both sites. The median follow-up time was 6.1 months for the RANU group and 47.8 months for the HANU group. The demographic and pathological data did not differ significantly. The RANU group had significantly less blood loss (), resumed oral intake earlier (), and had shorter hospital stays () but higher pain scores associated with their wounds (). The oncological outcomes were comparable with those of the HANU group. Conclusions. Our results show that the RANU and HANU groups have comparable operative, early postoperative, and functional outcomes. A longer follow-up period would be needed for final comparison of oncological outcome. Che-Yuan Hu, Cheng-Kuang Yang, Chao-Yuan Huang, Yen-Chuan Ou, Shun-Fa Hung, Shiu-Dong Chung, and Yeong-Shiau Pu Copyright © 2015 Che-Yuan Hu et al. All rights reserved. Candesartan Mediated Amelioration of Cisplatin-Induced Testicular Damage Is Associated with Alterations in Expression Patterns of Nephrin and Podocin Sun, 11 Oct 2015 09:40:22 +0000 Nephrin and podocin are known to be closely related to the pharmacological effects of angiotensin-II receptor blocker (ARB). The objectives of this study were to investigate the role of nephrin and podocin using cisplatin-induced testicular damage and to evaluate the effect of ARB. At first, we evaluated the effects of cisplatin either alone or in combination with ARB candesartan on changes in expression patterns of nephrin and podocin in the rat testes. We then conducted in vitro studies to investigate the effects of angiotensin using cultured Sertoli cells, line TM4. As a result, the expression of nephrin and podocin was shown to localize around the basal membrane of seminiferous tubules. Treatment with cisplatin resulted in a marked decrease in the expression of nephrin and podocin and induced a shift of both proteins from linear to granular expression patterns, accompanying the increased apoptotic index in the testes; these changes were partially restored by the additional administration of candesartan. In vitro studies with TM4 revealed the angiotensin-II mediated expression changes of nephrin and podocin. These findings suggest that candesartan can prevent cisplatin-induced testicular damage by regulating expression patterns of the nephrin-podocin complex in the testes. Noritoshi Enatsu, Hideaki Miyake, Koji Chiba, and Masato Fujisawa Copyright © 2015 Noritoshi Enatsu et al. All rights reserved. A Pilot Comparative Study of 26 Biochemical Markers in Seminal Plasma and Serum in Infertile Men Sun, 11 Oct 2015 09:16:28 +0000 Introduction. The relationships of the biochemical components in seminal plasma and serum, and their origins and physiological effects in male reproductive system have been poorly understood. Methods. Based on the calibration and quality control measures, 26 biochemical markers, in seminal plasma and serum samples from 36 male infertility patients with nonazoospermia were detected and compared. Results. Only PA was undetectable in all seminal plasma samples. There were significant differences of all other 24 biochemical markers in seminal plasma and serum () except for UA (). There were rich proteins in seminal plasma, and globulin accounted for about 90%. There were also abundant enzymes in seminal plasma, and the activities of ALT, AST, AKP, GGT, LDH, CK, and αHBDH in seminal plasma were significantly higher than those in serum while ADA was inversely lower. There were relatively low levels of Glu, TG, TC, and hsCRP in seminal plasma, but Glu was undetectable in 8 of 36 cases. Conclusions. The differences of the levels of biochemical markers in seminal plasma and serum might be associated with the selective secretion of testis, epididymis and male accessory glands, and the specific environment needed for sperm metabolism and function maintenance. Rui-Xiang Feng, Jin-Chun Lu, Hong-Ye Zhang, and Nian-Qing Lü Copyright © 2015 Rui-Xiang Feng et al. All rights reserved. The Significance of Metastasectomy in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy Sun, 11 Oct 2015 09:15:42 +0000 Objective. To investigate the efficacy of surgery in the treatment of metastatic renal cell carcinoma (mRCC) and to identify prognostic factors. Methods. A single center retrospective study of 96 patients with mRCC from December 2004 to August 2013. Results. The median follow-up time was 45 months. Thirty-one (32.3%) of the patients received complete resection of metastatic sites, 11 (11.5%) of the patients underwent incomplete resection of metastatic sites, and 54 (56.3%) of the patients received no surgery. In the univariate Kaplan-Meier analysis, the median overall survival times of the three groups were 52 months, 16 months, and 22 months, respectively (). The difference in the overall survival time was statistically significant between complete resection and no surgery groups (HR = 0.43, ), while there was no significant difference between the incomplete metastasectomy and no surgery groups (HR = 1.80, ). According to the multivariate Cox regression analysis, complete metastasectomy (HR = 0.49, ), T stage > 3 (HR = 1.88, ), disease free interval <12 months (HR = 2.34, ), and multiorgan involvement (HR = 2.00, ) were significant prognostic factors. Conclusion. In the era of targeted therapy, complete metastasectomy can improve overall survival. Complete metastasectomy, T stage > 3, disease free interval <12 months, and multiorgan involvement are independent prognostic factors. Xiaoteng Yu, Bing Wang, Xuesong Li, Gang Lin, Cuijian Zhang, Yang Yang, Dong Fang, Yi Song, Zhisong He, and Liqun Zhou Copyright © 2015 Xiaoteng Yu et al. All rights reserved. AR Pathway Is Involved in the Regulation of CX43 in Prostate Cancer Mon, 28 Sep 2015 09:06:12 +0000 CX43 plays a critical role in tumor progression. Previous studies imply that AR pathway may be involved in regulation of CX43. This study was focused on determining the relationship between AR pathway and CX43. The result showed that the expression of CX43 in malignant cells was higher than that in normal cells, and in nonmalignant and malignant cells, not only is the expression level of CX43 different, but the localization of CX43 can also be changed. After androgen stimulation and inhibition of AR pathway, expression of CX43 can also be changed. Thus, AR pathway plays an important role in regulation of CX43 expression in prostate cancer cells. AR may be the upstream signal of CX43. Ruibao Chen, Yang Luan, Zhuo Liu, Wen Song, Licheng Wu, Mingchao Li, Jun Yang, Xiaming Liu, Tao Wang, Jihong Liu, and Zhangqun Ye Copyright © 2015 Ruibao Chen et al. All rights reserved. Ultrastructural Morphology of Sperm from Human Globozoospermia Tue, 08 Sep 2015 09:18:23 +0000 Globozoospermia is a rare disorder characterized by the presence of sperm with round head, lacking acrosome. Coiling tail around the nucleus has been reported since early human studies, but no specific significance has conferred it. By contrast, studies on animal models suggest that coiling tail around the nucleus could represent a crucial step of defective spermatogenesis, resulting in round-headed sperm. No observations, so far, support the transfer of this hypothesis to human globozoospermia. The purpose of this work was to compare ultrastructural morphology of human and mouse model globozoospermic sperm. Sperm have been investigated by using scanning and transmission electron microscopy. The images that we obtained show significant similarities to those described in GOPC knockout mice, an animal model of globozoospermia. By using this model as reference, we were able to identify the probable steps of the tail coiling process in human globozoospermia. Although we have no evidence that there is the same pathophysiology in man and knocked-out mouse, the similarities between these ultrastructural observations in human and those in the experimental model are very suggestive. This is the first demonstration of the existence of relevant morphological homologies between the tail coiling in animal model and human globozoospermia. Giuseppe Ricci, Laura Andolfi, Giuliano Zabucchi, Stefania Luppi, Rita Boscolo, Monica Martinelli, Marina Zweyer, and Elisa Trevisan Copyright © 2015 Giuseppe Ricci et al. All rights reserved. Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma Thu, 03 Sep 2015 13:25:15 +0000 Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. Maria R. Ambrosio, Bruno J. Rocca, Aurora Barone, Monica Onorati, Lucia Mundo, Filippo Crivelli, Franca Di Nuovo, Giulia De Falco, Maria T. del Vecchio, Sergio A. Tripodi, and Piero Tosi Copyright © 2015 Maria R. Ambrosio et al. All rights reserved. Preoperative Neutrophil-to-Lymphocyte Ratio and Neutrophilia Are Independent Predictors of Recurrence in Patients with Localized Papillary Renal Cell Carcinoma Thu, 03 Sep 2015 11:47:28 +0000 Objective. To evaluate the role of preoperative neutrophil-to-lymphocyte ratio (NLR) and absolute neutrophil count (ANC) in patients’ prognosis with localized papillary renal cell carcinoma (pRCC). Methods. Data from 218 localized pRCC patients (T1-3 N0/+ M0), operated between 1991 and 2011 at two centers, were evaluated retrospectively. Univariable and multivariable analyses using the Cox regression model were performed to determine the associations of NLR and ANC with recurrence-free survival (RFS). Prognostic accuracy was evaluated with the Harrell concordance index. Results. The 5-year RFS rate was 87.0%. Multivariable analysis identified increased NLR (≥3.6) and ANC (≥5300/μL) as independent prognostic factors for RFS (hazard ratio (HR) = 4.01, ) and (HR = 4.71, ). The final model built by the addition of NLR or ANC improved predictive accuracy (c-index: 0.824, 0.842) compared with the clinicopathological base model (c-index: 0.800), which included TNM stage and tumor necrosis. Conclusions. The NLR and ANC appear to be independent prognostic factors for RFS after surgery for localized pRCC. They significantly increase the accuracy of established prognostic factors. Therefore, we recommend adding NLR and ANC to traditional prognostic model, which may improve its predictive accuracy. Jiwei Huang, Douglas M. Dahl, Liang Dong, Qiang Liu, Kristine Cornejo, Qi Wang, Shulin Wu, Adam S. Feldman, Yiran Huang, Wei Xue, and Chin-Lee Wu Copyright © 2015 Jiwei Huang et al. All rights reserved. iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum Biomarker for Renal Cell Carcinoma Thu, 03 Sep 2015 11:46:40 +0000 Renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about 80% of RCC are of the clear-cell type (ccRCC). However, there are no serum biomarkers for the accurate diagnosis of RCC. In this study, we performed a quantitative proteomic analysis on serum samples from ccRCC patients and control group by using isobaric tag for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins. Overall, 16 proteins were significantly upregulated (ratio > 1.5) and 14 proteins were significantly downregulated (ratio < 0.67) in early-stage ccRCC compared to control group. HSC71 was selected and subsequently validated by Western blot in six independent sets of patients. ELISA subsequently confirmed HSC71 as a potential serum biomarker for distinguishing RCC from benign urologic disease with an operating characteristic curve (ROC) area under the curve (AUC) of 0.86 (95% confidence interval (CI), 0.76~0.96), achieving sensitivity of 87% (95% CI 69%~96%) at a specificity of 80% (95% CI 61~92%) with a threshold of 15 ng/mL. iTRAQ-based quantitative proteomic analysis led to identification of serum HSC71 as a novel serum biomarker of RCC, particularly useful in early diagnosis of ccRCC. Yushi Zhang, Yi Cai, Hongyan Yu, and Hanzhong Li Copyright © 2015 Yushi Zhang et al. All rights reserved. Growth Pattern of Clear Cell Renal Cell Carcinoma in Patients with Delayed Surgical Intervention: Fast Growth Rate Correlates with High Grade and May Result in Poor Prognosis Thu, 03 Sep 2015 06:59:18 +0000 Objectives. Previous studies revealed an unclear correlation between the growth rate of renal cell carcinoma (RCC) and tumor grade and did not focus on certain histological subtype. This report investigated the correlation between the growth rate and tumor grade in clear cell RCC (ccRCC). Methods. We reviewed 60 patients with 61 ccRCC confirmed by delayed surgeries after at least 12 months of active surveillance. The linear growth rate (LGR), volumetric growth rate (VGR), and volume doubling time (VDT) were calculated, and their correlations with clinicopathologic characteristics were analyzed. Results. The mean LGR, VGR, and VDT were 0.86 (range 0–4.74) cm/year, 20.96 (range 0.31–211.93) cm3/year, and 667 (range 33–3321) days, respectively. ccRCCs with high grade had greater LGR () and VGR () and lower VDT () than ccRCCs with low grade. Grade (OR = 5.185, ) was the only independent risk factor of LGR >0.5 cm/year, and grade (OR = 3.006, ) and initial size (OR = 0.392, ) were independent risk factors of VDT <1 year. Five patients developed metastasis after surgery with LGR >0.5 cm/yr altogether; of them, four had cancer-related death by the last follow-up. Conclusions. Fast growth rate of ccRCC is significantly correlated with high tumor grade and may result in poor prognosis, especially for those with LGR >0.5 cm/yr. Lei Zhang, Wenshi Yin, Lin Yao, Xuesong Li, Dong Fang, Da Ren, Zhongyuan Zhang, Yu Fan, Qun He, Weimin Ci, Zhisong He, and Liqun Zhou Copyright © 2015 Lei Zhang et al. All rights reserved. Prognostic Outcomes and Risk Factors for Patients with Renal Cell Carcinoma and Venous Tumor Thrombus after Radical Nephrectomy and Thrombectomy: The Prognostic Significance of Venous Tumor Thrombus Level Thu, 03 Sep 2015 06:47:34 +0000 Introduction. To evaluate the prognostic outcomes and risk factors for renal cell carcinoma (RCC) patients with venous tumor thrombus in China. Materials and Methods. We reviewed the clinical information of 169 patients who underwent radical nephrectomy and thrombectomy. Overall and cancer-specific survival rates were analyzed. Univariate and multivariate analyses were used to investigate the potential prognostic factors. Results. The median survival time was 63 months. The five-year overall survival and cancer-specific survival rate were 53.6% and 54.4% for all patients. For all patients, significant survival difference was only observed between early (below hepatic vein) and advanced (above hepatic vein) tumor thrombus. However, significant differences existed between both RV/IVC and early/advanced tumor thrombus groups in N0M0 patients. Multivariate analysis demonstrated that higher tumor thrombus level (, ), N (, ), and M (, ) stages and adrenal gland invasion (, ) were the most significant negative prognostic predictors. Conclusions. In this study, we reported most cases of RCC patients with venous extension in China. We proved that patients with RCC and venous tumor thrombus may have relative promising long-term survival rate, especially those with early tumor thrombus. Qi Tang, Yi Song, Xuesong Li, Maxwell Meng, Qian Zhang, Jin Wang, Zhisong He, and Liqun Zhou Copyright © 2015 Qi Tang et al. All rights reserved. Initial Experience of Sorafenib Neoadjuvant Therapy Combined with Retroperitoneoscopy in Treating T2 Large Renal Carcinoma Thu, 03 Sep 2015 06:45:48 +0000 Objectives. To investigate the safety and feasibility of sorafenib neoadjuvant therapy combined with retroperitoneoscopic radical nephrectomy (RRN) in treating T2 large renal cell carcinoma (RCC). Methods. Retrospectively analyzed 5 cases (2 males and 3 females, aged 52–73 years) of T2 stage large RCC who receive preoperative sorafenib targeted treatment (400 mg bid for 1–3 months) and RRN between March, 2013, and July, 2014. Patient information, therapeutic regimen, drug adverse effect, tumor changes before and after surgery, and perioperative parameters were recorded. Results. During the sorafenib therapy adverse effects included 2 cases of hypertension (Grade I toxicity), 1 case of hand-foot syndrome (Grade I), and 1 case of diarrhea (Grade II), which were all tolerable for patients. CT scan and histopathological tests confirmed significant reduction in the longest dimension (LD) and medium density (MD) of the tumor after therapy as well as tumor hemorrhage, necrosis, and cystic degeneration. All 5 patients received RRN surgery successfully around 2 weeks after drug discontinuation with only 1 case of perioperative complication. Conclusions. Sorafenib neoadjuvant therapy could significantly reduce the size and aggressiveness of T2 large renal tumors, thus reducing the operative challenge and enabling patients who were previously disqualified for operation to receive surgical treatment. Chun-hua Lin, He-jia Yuan, Ke Wang, Ji-tao Wu, Qing-zuo Liu, Sheng-qiang Yu, Chang-ping Men, Zhen-li Gao, and Jiahui Wang Copyright © 2015 Chun-hua Lin et al. All rights reserved. Usefulness of Nonenhanced Computed Tomography for Diagnosing Urolithiasis without Pyuria in the Emergency Department Tue, 01 Sep 2015 12:58:24 +0000 We compared the clinical utility of nonenhanced computed tomography (NECT) and intravenous urography (IVU) in patients with classic symptoms of renal colic without evidence of a urine infection. This was a retrospective analysis of IVU and NECT performed in adult patients with suspected renal colic at an emergency department between January 2005 and December 2013. The records of all patients in NECT and IVU groups were reviewed, and the patients were categorized according to the cause of their symptoms. A total of 2218 patients were enrolled. Of these patients, 1525 (68.8%) underwent IVU and 693 (31.2%) underwent NECT. The patients in NECT group were older (45.48 ± 14.96 versus 42.37 ± 13.68 years, p < 0.001), had less gross hematuria (7.6 versus 2.9%, p < 0.001), and were admitted more often (18.6 versus 12.0%, p < 0.001) than the patients in IVU group. Urinary stones were detected in 1413 (63.7%) patients. NECT had a higher detection rate of urolithiasis than IVP (74.0 versus 59.0%, p < 0.001). No significant difference was observed in the incidence of urinary stones greater than 4mm between groups from the radiologic findings (p = 0.79) or the full medical record review (p = 0.87). Dong Hoon Lee, In Ho Chang, Jin Wook Kim, Byung Hoon Chi, and Sung Bin Park Copyright © 2015 Dong Hoon Lee et al. All rights reserved. Basic Fibroblast Growth Factor Ameliorates Endothelial Dysfunction in Radiation-Induced Bladder Injury Thu, 13 Aug 2015 12:13:25 +0000 This study was designed to explore the effect of basic fibroblast growth factor (bFGF) on radiation-induced endothelial dysfunction and histological changes in the urinary bladder. bFGF was administrated to human umbilical vein cells (HUVEC) or urinary bladder immediately after radiation. Reduced expression of thrombomodulin (TM) was indicated in the HUVEC and urinary bladder after treatment with radiation. Decreased apoptosis was observed in HUVEC treated with bFGF. Administration of bFGF increased the expression of TM in HUVEC medium, as well as in the urinary bladder at the early and delayed phases of radiation-induced bladder injury (RIBI). At the early phase, injection of bFGF increased the thickness of urothelium and reduced inflammation within the urinary bladder. At the delayed phase, bFGF was effective in reducing fibrosis within the urinary bladder. Our results indicate that endothelial dysfunction is a prominent feature of RIBI. Administration of bFGF can ameliorate radiation-induced endothelial dysfunction in urinary bladder and preserve bladder histology at early and delayed phases of RIBI. Shiwei Zhang, Xuefeng Qiu, Yanting Zhang, Kai Fu, Xiaozhi Zhao, Jinhui Wu, Yiqiao Hu, Weiming Zhu, and Hongqian Guo Copyright © 2015 Shiwei Zhang et al. All rights reserved. Comparison of National Institutes of Health-Chronic Prostatitis Symptom Index with International Index of Erectile Function 5 in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Large Cross-Sectional Study in China Mon, 27 Jul 2015 07:57:29 +0000 The purpose of the study is to evaluate the relationship between NIH-CPSI and IIEF-5 in Chinese men with CP/CPPS. A large cross-sectional and multicenter survey was conducted from July 2012 to January 2014. Men were recruited from urology clinics which were located at the five cities in China. All men participated in the survey by completing a verbal questionnaire (consisted of sociodemographics, past medical history, sexual history, and self-estimated scales). The results showed that 1,280 men completed the survey. Based on the CP/CPPS definition, a total of 801 men were diagnosed as having CP/CPPS. Men with CP/CPPS reported higher scores of NIH-CPSI and lower scores of IIEF-5 than men without CP/CPPS. NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. The total scores of NIH-CPSI were significantly more strongly correlated with question 5 than other questions of IIEF-5. The total scores of IIEF-5 were significantly more strongly correlated with pain symptoms scores of NIH-CPSI. Strongest correlation was found between QoL impact and question 5 of IIEF-5. The findings suggested that NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. Strongest correlation was found between QoL impact and question 5 of IIEF-5. Jingjing Gao, Pan Gao, Zongyao Hao, Zengrong Zhou, Jihong Liu, Hongjun Li, Junping Xing, Zhansong Zhou, Chunhua Deng, Liwen Deng, Qiang Wei, Xiansheng Zhang, Jun Zhou, Song Fan, Sheng Tai, Chen Yang, Kai Shi, Yuanyuan Huang, Zhangqun Ye, and Chaozhao Liang Copyright © 2015 Jingjing Gao et al. All rights reserved. Novel FGFR1 and KISS1R Mutations in Chinese Kallmann Syndrome Males with Cleft Lip/Palate Thu, 25 Jun 2015 07:09:32 +0000 Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism (IHH) with anosmia and is sometimes associated with cleft lip/palate (CLP). In order to describe the clinical features, genetic etiology, and treatment outcome of KS males with CLP, we performed genetic screening for 15 known causal IHH genes (KAL1, FGFR1, NELF, FGF8, CHD7, WDR11, SEMA3A, KISS1R, KISS1, PROKR2, PROK2, TAC3, TACR3, GNRH1, and GNRHR) in four KS with CLP patients and six IHH patients without CLP. Two novel heterozygous missense mutations in FGFR1, (NM_001174066): c.776G>A (p.G259E) and (NM_001174066): c.358C>T (p.R120C), were identified in a 23-year-old KS male with cleft lip and an 18-year-old KS patient with cleft lip and palate, dental agenesis, and high arched palate, respectively. These two mutations were not presented in their healthy parents and 200 normal controls. One novel heterozygous missense mutation in KISS1R, (NM_032551): c.587C>A (p.P196H), was identified in an 18-year-old KS male with cleft lip and dental agenesis who developed sperm after being treated with gonadotropin. This mutation was also presented in his healthy father and grandfather. These results have implications for the diagnosis, genetic counseling, and treatment of KS and CLP males with mutations in FGFR1 gene. Hao Xu, Yonghua Niu, Tao Wang, Simin Liu, Hua Xu, Shaogang Wang, Jihong Liu, and Zhangqun Ye Copyright © 2015 Hao Xu et al. All rights reserved. Relationship between Metabolic Syndrome and Lower Urinary Tract Symptoms: Hallym Aging Study Tue, 23 Jun 2015 11:25:31 +0000 The aim of the study was to test the hypothesis that the metabolic syndrome (MS) is linked to lower urinary tract symptoms (LUTS) in Korean men. This was a longitudinal study that used data collected from 328 men aged 50–89 years who were randomly selected among 1,520 participants in 2004. We collected information from 224 (68.3%) men among the original responders on the biological, medical, psychological, social, lifestyle, and economic factors in 2007. The prevalence of the MS was 187/328 (57.0%) in 2004 and 125/224 (55.8%) in 2007 among men, respectively. There was no significantly greater increase in the IPSS in men with the MS than in men without the MS over a 3-year period of time ( versus , , resp.). In the multivariate logistic regression analysis with control for age and life style factors, the risk factors for moderate/severe LUTS were age and erectile dysfunction (). However, the presence of the MS did not increase the risk of moderate/severe LUTS (OR = 1.09, 95% CI 0.63–1.89, ). Our cross-sectional and longitudinal risk factor analyses do not support the hypothesis that the MS is linked to LUTS in Korean men. Seong Ho Lee, Sang Kon Lee, Min Soo Choo, Kyung Tae Ko, Tae Young Shin, Won Ki Lee, Tsolmon Batsaikhan, ShanAi Quan, Jin Young Jeong, and Dong Hyun Kim Copyright © 2015 Seong Ho Lee et al. All rights reserved. Implants in Urogynecology Thu, 23 Apr 2015 06:56:44 +0000 Thomas Otto, Bernd Klosterhalfen, Uwe Klinge, Mihaly Boros, Dirk Ysebaert, and Koudy Williams Copyright © 2015 Thomas Otto et al. All rights reserved. Biomaterials for Pelvic Floor Reconstructive Surgery: How Can We Do Better? Tue, 21 Apr 2015 06:26:33 +0000 Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are major health issues that detrimentally impact the quality of life of millions of women worldwide. Surgical repair is an effective and durable treatment for both conditions. Over the past two decades there has been a trend to enforce or reinforce repairs with synthetic and biological materials. The determinants of surgical outcome are many, encompassing the physical and mechanical properties of the material used, and individual immune responses, as well surgical and constitutional factors. Of the current biomaterials in use none represents an ideal. Biomaterials that induce limited inflammatory response followed by constructive remodelling appear to have more long term success than biomaterials that induce chronic inflammation, fibrosis and encapsulation. In this review we draw upon published animal and human studies to characterize the changes biomaterials undergo after implantation and the typical host responses, placing these in the context of clinical outcomes. Giulia Gigliobianco, Sabiniano Roman Regueros, Nadir I. Osman, Julio Bissoli, Anthony J. Bullock, Chris R. Chapple, and Sheila MacNeil Copyright © 2015 Giulia Gigliobianco et al. All rights reserved. Complications following Tension-Free Vaginal Tapes: Accurate Diagnosis and Complications Management Mon, 20 Apr 2015 13:33:59 +0000 The sling procedures are the gold standard for SUI treatment. They are highly effective but not free from complications. The most common adverse effect for the surgery with the implant insertion is: overactive bladder occurring de novo after the surgery, voiding dysfunctions, urine retention, and unsatisfactory treatment outcome. The most important question that arises after 20 years of sling procedures is how to manage the complications and what can be offered to complicated patients. The above review summarises the ultrasound findings in complicated cases and shows the scheme of management of the clinical problems concerning the tape location in suburethral region. J. Kociszewski, S. Kolben, D. Barski, V. Viereck, and E. Barcz Copyright © 2015 J. Kociszewski et al. All rights reserved. High Structural Stability of Textile Implants Prevents Pore Collapse and Preserves Effective Porosity at Strain Mon, 20 Apr 2015 11:21:22 +0000 Reinforcement of tissues by use of textiles is encouraged by the reduced rate of recurrent tissue dehiscence but for the price of an inflammatory and fibrotic tissue reaction to the implant. The latter mainly is affected by the size of the pores, whereas only sufficiently large pores are effective in preventing a complete scar entrapment. Comparing two different sling implants (TVT and SIS), which are used for the treatment of urinary incontinence, we can demonstrate that the measurement of the effective porosity reveals considerable differences in the textile construction. Furthermore the changes of porosity after application of a tensile load can indicate a structural instability, favouring pore collapse at stress and questioning the use for purposes that are not “tension-free.” Uwe Klinge, Jens Otto, and Thomas Mühl Copyright © 2015 Uwe Klinge et al. All rights reserved. Global Convergence on the Bioethics of Surgical Implants Mon, 20 Apr 2015 09:02:50 +0000 The increasing globalization of mankind with pluralistic belief systems necessitates physicians by virtue of their profession to partner with bioethics for soundly applying emerging knowledge and technologies for the best use of the patient. A subfield within medicine in which this need is acutely felt is that of surgical implants. Within this subfield such recent promising ethics and medicine partnerships include the International Tissue Engineering Research Association and UNESCO Chair in Bioethics and Human Rights’ International Code of Ethics. In this paper, we provide an overview of the emerging human rights framework from bioethics and international law, discussion of key framework principles, their application to the current surgical challenge of implantation of surgical mesh for prolapse, and conclusions and recommendations. Such discussions are meant to facilitate true quality improvement in patient care by ensuring the exciting technologies and medical practices emerging new daily are accompanied by an equal commitment of physicians to ethically provide their services for the chief end of the patient’s good. Alberto Garcia and Dominique J. Monlezun Copyright © 2015 Alberto Garcia and Dominique J. Monlezun. All rights reserved. Management of Mesh Complications after SUI and POP Repair: Review and Analysis of the Current Literature Mon, 20 Apr 2015 06:46:20 +0000 Purpose. To evaluate the surgical treatment concepts for the complications related to the implantation of mesh material for urogynecological indications. Materials and Methods. A review of the current literature on PubMed was performed. Results. Only retrospective studies were detected. The rate of mesh-related complications is about 15–25% and mesh erosion is up to 10% for POP and SUI repair. Mesh explantation is necessary in about 1-2% of patients due to complications. The initial approach appears to be an early surgical treatment with partial or complete mesh resection. Vaginal and endoscopic access for mesh resection is favored. Prior to recurrent surgeries, a careful examination and planning for the operation strategy are crucial. Conclusions. The data on the management of mesh complication is scarce. Revisions should be performed by an experienced surgeon and a proper follow-up with prospective documentation is essential for a good outcome. D. Barski and D. Y. Deng Copyright © 2015 D. Barski and D. Y. Deng. All rights reserved. An Open Multicenter Study of Clinical Efficacy and Safety of Urolastic, an Injectable Implant for the Treatment of Stress Urinary Incontinence: One-Year Observation Mon, 20 Apr 2015 06:30:21 +0000 The prevalence of stress urinary incontinence rises and affects up to 30% of women after 50 years of age. Midurethral slings are currently the mainstay of surgical anti-incontinence therapy. Some patients experience recurrent SUI (RSUI) which is defined as a failure of anti-incontinence surgery after a period of time or persistence of SUI after the procedure aimed at correcting it. The urethral bulking agent application decreases invasiveness of treatment and meets patients requirements. The objective of this study was to assess the safety and clinical efficacy of Urolastic injection. One hundred and five patients with SUI (including 91 patients with RSUI) were treated with Urolastic in three tertiary gynecological clinics. The efficacy of the procedure was assessed objectively at each follow-up visit by means of cough test and a standard 1-hour pad test. Objective success rate after 12 months after primary procedure in RSUI patients was found in 59.3% of patients. In 14 patients with primary SUI improvement after 1 year was found in 71.4% of patients. Although cure rates after MUS are up to 90% there is still place for less invasive treatment option like periurethral injection of bulking agents, especially in patients with previous SUI surgical management. Konrad Futyma, Paweł Miotła, Krzysztof Gałczyński, Włodzimierz Baranowski, Jacek Doniec, Agnieszka Wodzisławska, Maciej Jóźwik, Małgorzata Oniszczuk, and Tomasz Rechberger Copyright © 2015 Konrad Futyma et al. All rights reserved. A Novel Operative Procedure for Pelvic Organ Prolapse Utilizing a MRI-Visible Mesh Implant: Safety and Outcome of Modified Laparoscopic Bilateral Sacropexy Sun, 19 Apr 2015 14:15:15 +0000 Introduction. Sacropexy is a generally applied treatment of prolapse, yet there are known possible complications of it. An essential need exists for better alloplastic materials. Methods. Between April 2013 and June 2014, we performed a modified laparoscopic bilateral sacropexy (MLBS) in 10 patients using a MRI-visible PVDF mesh implant. Selected patients had prolapse POP-Q stages II-III and concomitant OAB. We studied surgery-related morbidity, anatomical and functional outcome, and mesh-visibility in MRI. Mean follow-up was 7.4 months. Results. Concomitant colporrhaphy was conducted in 1/10 patients. Anatomical success was defined as POP-Q stage 0-I. Apical success rate was 100% and remained stable. A recurrent cystocele was seen in 1/10 patients during follow-up without need for intervention. Out of 6 (6/10) patients with preoperative SUI, 5/6 were healed and 1/6 persisted. De-novo SUI was seen in 1/10 patients. Complications requiring a relaparoscopy were seen in 2/10 patients. 8/10 patients with OAB were relieved postoperatively. The first in-human magnetic resonance visualization of a prolapse mesh implant was performed and showed good quality of visualization. Conclusion. MLBS is a feasible and safe procedure with favorable anatomical and functional outcome and good concomitant healing rates of SUI and OAB. Prospective data and larger samples are required. Ralf Joukhadar, Gabriele Meyberg-Solomayer, Amr Hamza, Julia Radosa, Werner Bader, Dimitri Barski, Fakher Ismaeel, Guenther Schneider, Erich Solomayer, and Sascha Baum Copyright © 2015 Ralf Joukhadar et al. 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. Early Continence Recovery after Preservation of Maximal Urethral Length until the Level of Verumontanum during Radical Prostatectomy: Primary Oncological and Functional Outcomes after 1 Year of Follow-Up Thu, 19 Sep 2013 11:43:17 +0000 Purpose. To investigate the effect of preventing maximal urethral length until the level of verumontanum during radical prostatectomy on both oncologic and functional outcomes. Patients and Methods. We recruited 329 patients, and they underwent an open radical prostatectomy by a single surgeon. The study cohort was randomized in 2 groups. A standard radical prostatectomy was performed in group A patients, while in group B the urethra was preserved until the level of verumontanum. Results. There was no statistically significant difference between the study groups in terms of positive surgical margins or biochemical relapse. Regarding the functional results, the incidence of incontinence, urgency, and nocturia at 1st month, statistically significant higher rates were seen in group A. In addition, there was a statistically significant difference in the number of pads/day in favor of group B at the 1st, 3rd, and 6th months after surgery. However, this difference was eliminated at 12 months postoperatively. Similar results were seen with the scores of the ICIQ-SF and IIQ-SF questionnaires. Conclusions. Without compromising the oncological outcome, our surgical modificated technique showed earlier recovery of continence in the first 6 months, having though the same rates of continence at 12 months. Stavros Sfoungaristos, Stavros Kontogiannis, and Petros Perimenis Copyright © 2013 Stavros Sfoungaristos 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.