The epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Two ZEB family members, ZEB1 and ZEB2(SIP1), inhibit transcription of the E-cadherin gene and induce EMT in vitro. However, their relevance to human cancer is insufficiently studied. Here, we performed a comparative study of SIP1 and ZEB1 proteins in cancer cell lines and in one form of human malignancy, carcinoma of the bladder. Whereas ZEB1 protein was expressed in all E-cadherin-negative carcinoma cell lines, being in part responsible for the high motility of bladder cancer cells, SIP1 was hardly ever detectable in carcinoma cells in culture. However, SIP1 represented an independent factor of poor prognosis (P ‫؍‬ 0.005) in a series of bladder cancer specimens obtained from patients treated with radiotherapy. In contrast, ZEB1 was rarely expressed in tumor tissues; and E-cadherin status did not correlate with the patients' survival. SIP1 protected cells from UV-and cisplatin-induced apoptosis in vitro but had no effect on the level of DNA damage. The anti-apoptotic effect of SIP1 was independent of either cell cycle arrest or loss of cell-cell adhesion and was associated with reduced phosphorylation of ATM/ATR targets in UV-treated cells. The prognostic value of SIP1 and its role in DNA damage response establish a link between genetic instability and metastasis and suggest a potential importance for this protein as a therapeutic target. In addition, we conclude that the nature of an EMT pathway rather than the deregulation of E-cadherin per se is critical for the progression of the disease and patients' survival. E pithelial mesenchymal transition (EMT) is a genetic program controlling cell migration during embryonic development and in wound healing (1, 2). Aberrant activation of EMT programs occurs in cells of epithelial tumors and contributes to the formation of cancer stem cells and metastasis (1-4). EMT is characterized by the loss of epithelial and the acquisition of mesenchymal features. EMT programs are controlled by several master regulators including TWIST, SNAIL (SNAI1 and SNAI2), and ZEB (ZEB1/␦EF1/TCF8 and SIP1/ZEB2) protein family members. These proteins act downstream in EMTinducing signal transduction pathways activated by growth factors, integrin engagement and hypoxia (1-3). Their expression is tightly regulated at the posttranscriptional level. Recent reports highlighted the importance of miR-200 microRNA family in the regulation of ZEB1 and SIP1 protein expression (5). ZEB proteins bind proximal E-boxes within the E-cadherin gene (cdh1) promoter and repress transcription by recruiting corepressor complexes (6). Likewise, they directly repress numerous genes encoding components of the epithelial junctional complex and cell polarity factors (7,8). The relevance of ZEB proteins to tumor progression has been studied in several forms of human cancer. Expression of ZEB1 correlated with the aggressive phenotype in various histological types of endometrial carcinoma and was detected in sarcomatous compartment of endometri...

Objectives: To review the causes and management of penile fracture and to compare between surgical and conservative management as well as immediate and delayed interventions in terms of overall and specific complications. Methods: A search of all reported literature was conducted for all articles reporting on the management and outcomes of penile fractures. Full texts of relevant articles were obtained and screened according to the inclusion criteria. Outcomes measures were numbers of patients receiving surgical or conservative management, aetiology of fracture, length of admission, complications as well as the specifics of diagnostic approaches and operative management. Data was collated and where possible meta-analysed using Revman software. Results: A total of 58 relevant studies involving 3,213 patients demonstrated that intercourse accounts for only 48% of cases with masturbation and forced flexion accounting for 39%. Meta-analysis shows that surgical intervention was associated with significantly fewer complications vs. conservative management (p < 0.000001). Surgical intervention results in significantly less erectile dysfunction (ED), curvature and painful erection than conservative management. There was no significant difference in the number of patients developing plaques/nodules (p = 0.94). Meta-analysis shows that overall early surgery is preferable to delayed surgery but that rates of ED are not significantly different. Discussion: Early surgical intervention is associated with significantly fewer complications than conservative management or delayed surgery. The combined outcome of rapid diagnosis by history and clinical examination and swift surgical intervention is key for reconstruction with minimal long-term complications.

Introduction: There is a growing concern about the reduced clinical exposure to urology at undergraduate level in the United Kingdom. As a consequence, the competencies of junior doctors are considered inadequate. The views of these doctors in training towards urology remain under reported. Methods: A modified Delphi method was employed to construct a questionnaire. Given the rise of social media as a platform for scientific discussion, participants were recruited via a social networking site. Outcomes assessed included career preference, exposure to urology, perceived male dominance, and confidence at core procedures. Results: In total, 412 and 66 responses were collected from medical students and junior doctors, respectively. Overall, 41% of participants felt that they had received a good level of clinical exposure to urology as part of their training and 15% were considering a career in this speciality. Female students were significantly less likely to consider urology as a career option (p < 0.01). Of these, 37% of the students felt confident at male catheterization and 46% of students regarded urology as a male-dominated speciality. Conclusions: Urology is perceived as male dominated and is the least likely surgical speciality to be pursued as a career option according to our survey. Increased exposure to urology at the undergraduate level and dedicated workshops for core urological procedures are needed to address these challenges.

The initial results of the outcome of RALP are at least at par with those of LRP and with those of previously published RALP series. This suggests the lack of a steep learning curve for experienced laparoscopic surgeons in performing RALP.

Objective To compare the clinical validity and utility of Likert assessment and the Prostate Imaging Reporting and Data System (PI‐RADS) v2 in the detection of clinically significant and insignificant prostate cancer. Patients and Methods A total of 489 pre‐biopsy multiparametric magnetic resonance imaging (mpMRI) scans in consecutive patients were subject to prospective paired reporting using both Likert and PI‐RADS v2 by expert uro‐radiologists. Patients were offered biopsy for any Likert or PI‐RADS score ≥4 or a score of 3 with PSA density ≥0.12 ng/mL/mL. Utility was evaluated in terms of proportion biopsied, and proportion of clinically significant and insignificant cancer detected (both overall and on a ‘per score’ basis). In those patients biopsied, the overall accuracy of each system was assessed by calculating total and partial area under the receiver‐operating characteristic (ROC) curves. The primary threshold of significance was Gleason ≥3 + 4. Secondary thresholds of Gleason ≥4 + 3, Ahmed/UCL1 (Gleason ≥4 + 3 or maximum cancer core length [CCL] ≥6 or total CCL≥6) and Ahmed/UCL2 (Gleason ≥3 + 4 or maximum CCL ≥4 or total CCL ≥6) were also used. Results The median (interquartile range [IQR]) age was 66 (60–72) years and the median (IQR) prostate‐specific antigen level was 7 (5–10) ng/mL. A similar proportion of men met the biopsy threshold and underwent biopsy in both groups (83.8% [Likert] vs 84.8% [PI‐RADS v2]; P = 0.704). The Likert system predicted more clinically significant cancers than PI‐RADS across all disease thresholds. Rates of insignificant cancers were comparable in each group. ROC analysis of biopsied patients showed that, although both scoring systems performed well as predictors of significant cancer, Likert scoring was superior to PI‐RADS v2, exhibiting higher total and partial areas under the ROC curve. Conclusions Both scoring systems demonstrated good diagnostic performance, with similar rates of decision to biopsy. Overall, Likert was superior by all definitions of clinically significant prostate cancer. It has the advantages of being flexible, intuitive and allowing inclusion of clinical data. However, its use should only be considered once radiologists have developed sufficient experience in reporting prostate mpMRI.

In early experience, RRC appears to be feasible and a safe alternative to the ORC. RRC appears to have lower high-grade complications and mortality rates compared with the open approach. Although these results are promising, the authors would suggest caution while interpreting these results due to concerns with methodological flaws in the included studies in this review.

The robot-assisted approach is efficient in the performance of ureteral reimplantation with Boari flap. Low blood loss, short catheterization time, low complication rate, and excellent reconstructive outcome are associated with the approach. Robot assistance seems to be beneficial for ureteral reconstructive surgery.

ObjectiveTo describe our robot-assisted Boari flap ureteric reimplantation (RA-BFUR) technique, Please see Video S1. MethodsThe RA-BFUR technique is based on the open surgical technique of € Ubelh€ or, and the experience includes 11 cases. ResultsExcellent results were achieved after a mean follow-up period of >12 months. ConclusionThe RA-BFUR technique could be considered a safe and effective method of ureteric reimplantation for long distal ureteric strictures.