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Prostate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. It emerges through the acquisition of genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications and microRNA deregulation. These generate heritable transformations in the expression of genes but do not change the DNA sequence. Alterations in DNA methylation (hypo and hypermethylation) are the most characterized in PCa. They lead to genomic instability and inadequate gene expression. Major and minor-specific modifications in chromatin recasting are involved in PCa, with signs suggesting a dysfunction of enzymes modified by histones. MicroRNA deregulation also contributes to the initiation of PCa, including involvement in androgen receptor signalization and apoptosis. The influence of inflammation on prostate tumor carcinogenesis is currently much better known. Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation, promoting prostate inflammatory atrophy and eventually leading to PCa. Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa. The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis, treatment decisions, evaluation of prognosis and posttreatment surveillance. info:eu-repo/semantics/publishedVersion

INTRODUCTION: Acute oncology services (AOS) provide rapid review and expedited pathways for referral to specialist care for cancer patients. Blood tests may support AOS in providing estimates of prognosis. We aimed to develop and validate a prognostic model of 30-day mortality based on routine blood markers to inform an AOS decision to actively treat or palliate patients. METHODS AND MATERIALS: Using clinical data from 752 AOS referrals, multivariable logistic regression analysis was conducted to develop a 30-day mortality prognostic model. Internal validation and then internal-external cross-validation were used to examine overfitting and generalizability of the model's predictive performance. RESULTS: Urea, alkaline phosphatase, albumin and neutrophils were the strongest predictors of outcome. The model separated patients into distinct prognostic groups from the cross-validation (C Statistic: 0.70; 95% CI: 0.64-0.76). Admission year was included as a predictor in the model to improve the model calibration. CONCLUSION: The developed prediction model was able to classify patients into distinct prognostic risk groups, which is clinically useful for delivering an evidence-based AOS. Collation of data from other AOS centers would allow for the development of a more generalizable prognostic model.

To determine current practice patterns and adherence to various components of enhanced recovery after surgery in cystectomy (ERAC) protocol for peri-operative management of radical cystectomy patients through a global survey.A survey containing 25 questions and addressing 15 of the 22 items of the ERAC protocol was developed and disseminated through Email to the urologists with recent bladder cancer publications. The mailing list was generated by retrieving Email-ids of corresponding authors of articles using the keyword "cystectomy" in Scopus from January 2018 to October 2020.The survey was completed by 443 respondents across the globe. About 51.5% of respondents used some form of bowel preparation. A minority used carbohydrate loading (29.8%) and Alvimopan (13.3%). A short duration of nil by mouth was practised by 28.9%. For antibiotic prophylaxis, 51.7% used one, and 42% used two antibiotics. Duration of antibiotics was 24 hours, 48 hours, and48 hours for 47.6%, 16.9%, and 35.4%, respectively. For peri-operative analgesia, 43.6% used non-steroidal anti-inflammatory drugs, 9.3% opioids and 40.6% combination of both. Pharmacological thrombo-prophylaxis was routinely used by 74.7% respondents. There was significant variability in ERAC and non-ERAC components according to region of practice; The open surgical approach was most commonly used in Africa (92%), whereas it was the robotic approach in North America (or America?) (41%). The use of bowel preparation was higher in Asia (58%) and Africa (65%). Alvimopan use was more common in North America (58%). Most used 1 or 2 prophylactic antibiotics but the duration was shorter (24 hours) in the Americas and European (58%-83%) compared to Asia and Africa (15%-35%).There is high variability in the use of different ERAC components. Other than the timely removal of the abdominal drain and the use of thromboprophylaxis, the overall adherence of ERAC components is low.

This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of investigate surgery on 09 July 2019. Final version including figures, is available online: https://doi.org/10.1080/08941939.2019.1637038. Purpose: To compare two clinically relevant anesthetic agents, i.e., isoflurane versus propofol with respect to protection of the kidney in a porcine renal ischemia reperfusion model. Materials and Methods: 14 hybrid pigs were randomized to anesthesia with either isoflurane or propofol prior to laparoscopic surgery. Following anesthesia, the left kidney hilum was clamped for 60 min and the right kidney removed. After 48 h of reperfusion, urine was sampled for analysis of neutrophil gelatinase-associated lipocalin (NGAL), albumin, and creatinine. The left kidney was harvested for histologic scoring of injury. Results: Histologic examination of renal injury revealed a statistically significant difference in favor of isoflurane on denuded basement membrane score (isoflurane group 1.58 ± 0.38 vs. propofol 2.42 ± 0.80, p = .026). Median (25–75 percentile) urinary albumin 3.4 g/L (2.25–7.48) vs. 8.9 g/L (3.73–13.8), (p = .041) and urinary albumin/creatinine ratio 1.17 (0.76–1.82) vs. 1.76 (1.63–5.99), (p = .026) were both significantly lower in the isoflurane group. Median (25–75 percentile) urinary NGAL was 167 (51–215) pg/ml in the isoflurane group compared with 362 (149–508) pg/ml in the propofol group (p = .093). Conclusion: Isoflurane increases tolerance to renal ischemia reperfusion injury compared to propofol in this model.

Background. Telementoring is a technique that has shown potential as a surgical training aid. Previous studies have suggested that telementoring is a safe training modality. This review aimed to review both the technological capabilities of reported telementoring systems as well as its potential benefits as a mentoring modality. Methods. A systematic review of the literature, up to July 2017, was carried out in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Study quality was assessed using the Oxford Levels of Evidence proforma. Data were extracted regarding technical capabilities, bandwidth, latency, and costs. Additionally, the primary aim and key results were extracted from each study and analyzed. Results. A total of 66 studies were identified for inclusion. In all, 48% of studies were conducted in general surgery; 22 (33%), 24 (36%), and 20 (30%) of studies reported telementoring that occurred within the same hospital, outside the hospital, and outside the country, respectively. Sixty-four (98%) of studies employed video and audio and 38 (58%) used telestration. Twelve separate studies directly compared telementoring against on-site mentoring. Seven (58%) showed no difference in outcomes between telementoring and on-site mentoring. No study found telementoring to result in poorer postoperative outcomes. Conclusions. The results of this review suggest that telementoring has a similar safety and efficacy profile as on-site mentoring. Future analysis to determine the potential benefits and pitfalls to surgical education through telementoring are required to determine the exact role it shall play in the future. Technological advances to improve remote connectivity would also aid the uptake of telementoring on a larger scale.

Dissection of the pudendal nerve (PN) and its branches in 71 cadavers revealed anatomic variations not previously described. Knowledge of this variation is necessary to prevent nerve injury resulting in sexual of sensory dysfunction. Because descriptions vary, this study re-evaluated the anatomy of the PN as implicated in perineal procedures in South Africans. The course of the PN from the gluteal region into the perineum was dissected in an adult sample of both sexes and of African and European ancestry. Distances between PN and branches to applicable landmarks were measured. Basic descriptive statistics and comparisons were carried out between groups. In 5/13 African females, the inferior rectal nerve (IRN) entered the gluteal region separately and in 12/13 cases it passed medial to the ischial spine with the PN. The dorsal nerve of the clitoris or penis (DNC/DNP) was closer to the bony frame in those of European ancestry. The IRN branches were more superficial in females, but deeper in males of European ancestry. In African females, a PN block and Richter stitch should be placed more medial. Outside-in transobturator tape procedures might endanger the DNC/DNP in obese individuals. In females of European ancestry the IRN branches are compromised during ischioanal abscess drainage. In males of European ancestry, the dorsal penile nerve block might be less effective. Predictions should be verified clinically.

Source at https://doi.org/10.1038/s41598-017-16556-2 . Due to insufficient prognostic tools, failure to predict aggressive prostate cancer (PC) has left patient selection for radical treatment an unsolved challenge. This has resulted in overtreatment with radical therapy. Better prognostic tools are urgently warranted. MicroRNAs (miRs) have emerged as important regulators of cellular pathways, resulting in altered gene expressions. miR-205 has previously been observed downregulated in PC, acting as tumor suppressor. Herein, the expression of miR-205 in prostate tissue was examined in a large, well-described cohort of 535 Norwegian prostatectomy patients. Using in situ hybridization, miR-205 expression was semiquantatively measured in normal and tumor tissues from radical prostatectomy specimens. Associations with clinicopathological data and PC relapse were calculated. Expression of miR-205 was lower in tumor epithelium compared to normal epithelium. No association was observed between miR-205 expression in primary tumor epithelium and cancer relapse. In contrast, high expression of miR-205 in normal epithelium was independently associated with biochemical relapse (HR = 1.64, p = 0.003). A prognostic importance of miR-205 expression was only found in the normal epithelium, raising the hypothesis of epithelial crosstalk between normal and tumor epithelium in PC. This finding supports the proposed novel hypothesis of an anti-cancerogenous function of normal epithelium in tumor tissue.

Few quantifiable tissue biomarkers for the diagnosis and prognosis of prostate cancer exist. Using an unbiased, quantitative approach, this study evaluates the potential of three proteins of the 40S ribosomal protein complex as putative biomarkers of malignancy in prostate cancer. Prostate tissue arrays, constructed from 82 patient samples (245 tissue cores, stage pT3a or pT3b), were stained for antibodies against three ribosomal proteins, RPS19, RPS21 and RPS24. Semi-automated Ox-DAB signal quantification using ImageJ software revealed a significant change in expression of RPS19, RPS21 and RPS24 in malignant vs non-malignant tissue (p

Source: doi: 10.1038/srep43378 Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-β, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-β was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-β was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-β expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-β may help distinguish which patients will benefit from radical treatment, and since PDGFR-β is associated with relapse and shorter survival, it mandates a focus as a therapeutic target.

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes.

PURPOSE: Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery. OBJECTIVES: The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group. EVIDENCE ACQUISITION: A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated. EVIDENCE SYNTHESIS: Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery. CONCLUSIONS: ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.

Objective To report and identify the predictors of early and long-term complications in a large series of extraperitoneal robot-assisted radical prostatectomy using the standardized Martin criteria. MaterialS and Methods A total of 1503 patients underwent extraperitoneal robot-assisted radical prostatectomy for the treatment of clinically localized prostate cancer from July 2003 to August 2010 at a tertiary referral center. The median follow-up was 28.9 months. Fisher’s exact test was used to examine the association of multiple variables in a bivariate analysis with the incidence and types of complications. Independent predictors were also examined in a multivariate analysis using logistic regression models. Results A total of 151 complications were recorded in 127 of 1503 patients (8.45%). Approximately one third (30.5%) were classified as major complications requiring intervention (Clavien grade III and IV). The most commonly encountered complications were lymphocele (1.46%), bladder neck contracture (1.33%), and anastomotic leak (1.20%). The operative time was a significant predictor of all complications and of major complications on multivariate analysis. Surgeon experience was also predictive of complications on multivariate analysis. Conclusion Extraperitoneal robot-assisted radical prostatectomy remains an underused alternative approach for the treatment of localized prostate cancer. Its safety profile is equivalent to that of other approaches in experienced hands.

Robotic technologies have had a significant impact on surgery. We report what is to our knowledge the first use of microrobots to perform laparoscopic urological surgery in a canine model.Nonsurvival laparoscopic radical prostatectomy and radical nephrectomy were performed using microrobotic camera assistance. Following the administration of general anesthesia miniature camera robots were inserted in the insufflated abdomen via a 15 mm laparoscopic port. These microrobots were mobile, controlled remotely to desired locations and provided views of the abdominal cavity, assisting the laparoscopic procedures. Additional ports and laparoscopic instruments were placed in the abdomen using the views provided by these microrobots.One dog underwent laparoscopic prostatectomy and another underwent laparoscopic nephrectomy. The 2 procedures were completed successfully. Microrobots provided additional views from several angles, aiding in the performance of the procedures.Miniature camera robots (microrobots) provide a mobile viewing platform. With added functionality these new robots have the potential to further evolve the robotic armamentarium for surgeons.

New technologies are regularly being used for surgical treatment of prostate cancer, however the cost associated is often a secondary issue. We assessed the operative costs incurred by using the daVinci robot assisted prostatectomy (RAP) method compared to pure laparoscopic radical prostatectomy (LRP) and open radical prostatectomy (ORP). We retrospectively analyzed three techniques of radical prostatectomies: ORP, LRP, and RAP (n = 70, 57, 106, respectively). The mean patient age was 53.6, 57.6, and 60 with a mean preoperative prostate specific antigen (PSA) of 7.2, 8.4, and 6.6, respectively. The mean Gleason score was 6. Operative cost was measured for each patient. Charts were reviewed to assess individual patients postoperative requirements, and hospital length of stay (LOS). Intraoperative data show costs to be higher with the RAP and LRP compared to open surgery. Average total operating room (OR) costs per case were $5410, $3876, and $1870 for RAP, LRP, and open prostatectomy, respectively. However when comparisons are made in the postoperative period with regard to LOS, there is a significant advantage of the RAP and LRP groups over open surgery (P

Although extraperitoneal robot-assisted radical prostatectomy (RARP) is gaining popularity, the majority of these procedures are performed transperitoneally. The purpose of this study was to compare the transperitoneal and extraperitoneal approaches for RARP.We randomized 62 consecutive patients undergoing RARP into two equal groups according to the route of access. The groups were evaluated for age, body mass index (BMI), preoperative serum prostate specific antigen (PSA) concentration, total operating time, estimated blood loss, specimen weight, pathologic Gleason score and stage, intraoperative and postoperative complications, and surgical-margin status.No significant differences were noted the extraperitoneal and transperitoneal groups with respect total operative time (181 v 191 minutes), blood loss (199 v 163 mL), pathologic Gleason score (6.6 v 6.7), specimen weight (53 v 48 g), or positive-margin status (0 v 1 patient). There were no significant differences in age (56 v 59 years) or PSA (7.8 v 6.1 ng/dL). However, the BMI was significantly higher in the extraperitoneal group (29.8 v 26.5 kg/m(2); P0.01). The only complication in the study was a urine leak, which occurred in the transperitoneal group and was managed conservatively.There were no significant differences in operative parameters in the two groups. Choice of access should be based on patient characteristics as well as surgeon preference. Patients who have had abdominal operations are best suited for the extraperitoneal route. Surgeons should be familiar with both approaches in order to provide patients with the best care.

Objectives: We review important aspects of nanotechnology, and discuss the wide range of research and clinical applications of nanomedicine in the field of urology. There is particular emphasis on key clinical and pre-clinical studies to provide an update on recent and potential applications in the care of urological patients. Methods: A directed Medline literature review of nanotechnology was performed. Important publications that have shaped our understanding of nanotechnology were selected for review and were augmented by manual searches of reference lists. Results: Nanotechnology is the study, design, creation, synthesis, manipulation, and application of functional materials, devices, and systems through control of matter at the nanometer scale. Studies demonstrate a number of important concepts. These include nanovectors, nanotubes, and nanosensors for targeted drug delivery; nanowires and nanocantilever arrays for early detection of precancerous and malignant lesions; and nanopores for DNA sequencing. These advances will lead to significant applications relevant to the diagnosis, management, and treatment of all urological conditions. Conclusions: This review is designed for the urologist to provide an overview and update on nanotechnology and its applications in the field of urology. In the future, it is widely expected that nanotechnology and nanomedicine will have a significant impact on urological research and clinical practice, allowing urologists to intervene at the cellular and molecular level. With structured, safe implementation, nanotechnologies have the potential to revolutionise urological practice in our lifetime.

A large prostate can complicate an extraperitoneal robot-assisted radical prostatectomy (RARP). We report our experience with RARP and evaluate the effects of prostate size on treatment outcomes after extraperitoneal RARP.Information on 355 consecutive patients undergoing extraperitoneal RARP was gathered, and patients with prostate weight75 g (N = 319) were compared with those having glandsor=75 g (N = 36). The factors considered were age, body mass index, total operating time, estimated blood loss, serum prostate specific antigen (PSA) concentration, pathologic stage and Gleason grade, intraoperative and peri-operative complications, margin status, and continence.A statistically significant difference (P0.05) was noted in age (59 v 64 years), PSA concentration (6.07 v 8.9 ng/dL), and blood loss (175 v 226 mL) between patients with smaller v larger prostates. No difference was seen in Gleason score (6 v 6), clinical T stage, operative time (217 v 225 minutes), or total positive-margin rate (13% v 19%). A higher positive-margin rate was seen in patients with stage T(3) disease and larger prostates. The 6-month continence rate in patients with a prostate volume75 g was 97% v 84% in patients with larger prostate volumes ( P0.05).Although a large prostate volume is associated with a slight increase in short-term urinary complications postoperatively, it should not be considered a contraindication for the experienced surgeon. This higher risk raises the question of a possible need for longer catheterization in this subset of patients.

Totally intracorporeal robotic-assisted radical cystectomy (RARC) has perceived difficulties compared to open radical cystectomy (ORC). As the technique is increasingly adopted around the world, the benefits of RARC with intra- or extracorporeal urinary diversion or ORC for the patients are still unclear. In this article, we consider the current evidence for this issue. We assessed two questions through using expert opinion and the medical literature: (A) Is RARC better than ORC for removing the cancer surgery and outcome? (B) Is RARC better than ORC for the urinary diversion? (A) RARC is better than ORC for shorter length of stay, blood loss and complication rates. (B) Intracorporeal orthotopic neobladder may have a significant physiological and surgical benefit to the patient recovery. RARC with total intracorporeal reconstruction has potential benefits to the patient. We recommend that all surgeons document patient-related outcome measures, urodynamics and enhanced recovery protocols for cystectomy patients to help us understand the real improvements within bladder cancer surgery and reconstruction.

Publisher's version, source: http://dx.doi.org/10.1371/journal.pone.0124395 . Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p

In the first part of this review the potential pathophysiological factors involved in the overactive bladder were outlined, and the wide range of first-line anticholinergic pharmacotherapies available for such patients were reviewed. The second part will focus on the intravesical instillation of resiniferatoxin and injections of botulinum toxin into the bladder to treat overactive bladder and detrusor overactivity. Resiniferatoxin has been shown to increase bladder capacity and improve incontinence in patients with neurogenic and non-neurogenic detrusor overactivity. Botulinum toxin has successfully been used to treat neurogenic and idiopathic detrusor overactivity, with improvements observed in bladder capacity, decreases in detrusor pressures on filling and voiding, and increased volumes at first contraction. Further validation is required for both treatments, in the form of large randomised controlled trials, before their use can be considered routine, with particular focus on dosing required.

Laparoscopic radical prostatectomy with or without a robot has been increasingly performed worldwide, primarily using a transperitoneal approach. We report our experience with daVinci(R) robot assisted extraperitoneal laparoscopic radical prostatectomy.A total of 325 patients underwent robot assisted extraperitoneal laparoscopic radical prostatectomy for clinically localized prostate cancer at our center during a 2-year period. Perioperative data, and oncological and functional results were prospectively recorded.Perioperative demographics included mean age, PSA and Gleason score, which were 60 years (range 42 to 76), 6.6 ng/ml (range 0.6 to 26) and 6 (range 5 to 9), respectively. Preoperative clinical stage was 81%, 16% and 3% for T1c, T2a and T2b, respectively. Average total operative time was 130 minutes (range 80 to 480). Intraoperative data included a mean blood loss of 196 cc with no open conversions. Bilateral, unilateral and nonnerve sparing prostatectomy was performed in 70%, 24% and 6% of patients, respectively. Of the patients 96% were discharged home within 8 to 23 hours of surgery. Pathological stage was pT2a, pT2b, pT3a and pT3b in 18%, 63%, 14% and 5% of all radical prostatectomy specimens, respectively, with an overall positive surgical margin rate of 13%. Two of 92 patients had positive nodal disease after lymph node dissection. Continence and erectile function were measured.The extraperitoneal approach offers the advantages of improved dexterity and visualization of the robot, while avoiding the abdominal cavity and potential associated morbidity. As surgeons gain more experience with this new technology, the extraperitoneal approach simulating the standard open retropubic technique is likely to gain popularity.

Metastatic renal cell carcinoma (RCC) is resistant to conventional chemotherapy and radiotherapy. However, immunotherapy appears to be effective in 15—20% of cases, with interleukin-2 becoming the standard therapy for this disease. As a consequence of the immune susceptibility of RCC, other avenues of immunotherapy are being explored, such as nonmyeloablative allogeneic stem cell transplantation (NST). A number of trials have shown NST to be effective in varying degrees, causing partial or complete regression. Although nonmyeloablative conditioning is safer than myeloablative conditioning, its role has yet to be clearly proven as many studies have shown variable effect. Alongside this limitation, transplant-related toxicity also forms obstacles. Regardless of the limitation of NST, further refinement of the technique, with appropriate patient selection, may lead to this being an effective therapeutic choice for a significant number of individuals.

Real-time quantitative PCR allows the sensitive, specific and reproducible quantitation of nucleic acids. Since its introduction, real-time quantitative PCR has revolutionized the field of molecular diagnostics and the technique is being used in a rapidly expanding number of applications. This exciting technology has enabled the shift of molecular diagnostics toward a high-throughput, automated technology with lower turnaround times. This article reviews the basic principles of real-time PCR and describes the various chemistries available: the double-stranded DNA-intercalating agent SYBR Green 1, hydrolysis probes, dual hybridization probes, molecular beacons and scorpion probes. Quantitation methods are discussed in addition to the competing instruments available on the market. Examples of applications of this important and versatile technique are provided throughout the review.

Prostate stem cell antigen gene was originally identified through an analysis of genes upregulated in the human prostate cancer LAPC-4 xenograft model. PSCA was named inaccurately since it is not a marker for a stem cell population nor is it exclusively expressed in the prostate. The function of PSCA in normal cellular processes or carcinogenesis is currently unknown.

Summary Metastatic renal-cell carcinoma (RCC) is resistant to chemotherapy, and patients with this disease have a poor outlook. Immunotherapy by use of cytokines and vaccines against tumour antigens has shown encouraging results in a small group of patients. Advances in the understanding of the graft-versus-tumour effect in haematological malignant disorders have led to the use of stem-cell transplantation for treatment of solid-organ malignant diseases such as RCC. Techniques of bone-marrow ablation have been superseded by safer conditioning regimens, with occasional complete remission and partial remission in some patients. Graftversus- host disease, engraftment failure, and disease progression remain important obstacles to the widespread use of new techniques for metastatic RCC. Here, we summarise important issues surrounding immunotherapy for RCC, the problems encountered with use of immunotherapy, and the present use of non-myeloablative techniques for treatment of this disease.

Peyronie's disease (PD) is characterised by penile plaque formation, pain, penile deformity and erectile dysfunction. It is a fibrotic disorder of the tunica albuginea with a poorly understood aetiology and epidemiology. PD may be classified into inflammatory (acute) and chronic stages. Medical treatment is usually instigated during the inflammatory phase of the disease. A review of the literature reveals a wide range of oral, intralesional and alternative therapies that are discussed in relation to established pathophysiological mechanisms of the disease. The advantages and disadvantages of each treatment are summarised. This review also discusses the ongoing therapeutic dilemmas of PD and suggests a treatment strategy based on an analysis of the urological literature.

Priapism is characterised by the presence of prolonged, often painful penile erection in the absence of a sexual stimulus. This rare condition has a range of aetiologies, but is most common following self-administration of injection therapy for impotence. Priapism may be classified into high- and low-flow states. Low-flow priapism is an emergency ischaemic condition requiring prompt recognition and treatment to avoid devastating long-term complications of erectile dysfunction. Wide-ranging medical therapies are covered in this review. Diagnostic and treatment algorithms are suggested in light of the current available literature.

OBJECTIVE To highlight the importance of methodological standards in diagnostic testing in urology, by reviewing the extent of compliance with these standards in reports of published evaluations. METHODS Sixteen papers evaluating the diagnostic accuracy of urinary flow-rate testing were independently assessed by two reviewers for compliance with the following methodological standards: specification of study population, analysis of pertinent subgroups, avoidance of evaluation (verification) bias, avoidance of review bias, reporting of precision of estimates of test accuracy, indeterminate test results, and test reproducibility. Compliance with each standard was expressed as a percentage with a 95% confidence interval. RESULTS Compliance ranged from just 12.5 (1.5-38)% for reporting of test reproducibility to 87.5 (62-98)% for specification of the study population. Only nine of the 16 evaluations complied with four or more of the methodological standards; one paper did not comply with any. CONCLUSIONS This evaluation of urological flow-rate testing show poor compliance with accepted methodological standards. The study design, reporting and evaluation of new diagnostic tests can be improved by adhering to these standards. Policy-makers, purchasers and providers would be less likely to adopt new diagnostic tests inappropriately if they were to appraise published evaluations against the standards. A reduction in the inappropriate use of tests would in turn lead to more cost-effective use of healthcare resources.

A retrospective analysis of our seven-year experience with the Memokath urethral stent for the treatment of detrusor sphincter dyssynergia (DSD) in spinal cord injured (SCI) patients.Twenty five patients with SCI underwent rhabdosphincter Memokath stent insertion. The mean age was 45.5 years (range 32-65 years). The level of injury was cervical in 14 and thoracic in 11 patients. All patients were shown to have neurogenic detrusor overactivity with DSD associated with high detrusor pressures and incomplete emptying on pre-operative video-cystometrograms (VCMG). The Memokath stent was inserted using a standardized protocol. Follow-up assessment included blood chemistry, ultrasound scan (upper tracts and residual urine) at one and three months after insertion, and a follow-up VCMG at six months. The pre-operative and six-month post-operative VCMG results were analysed by the paired t-test and p value0.05 was taken as significant.There was a significant reduction in maximum detrusor pressure, duration of contraction and residual urine volume (p0.05) on the VCMG six months after insertion of the stent. At present six patients have a Memokath stent in situ at a mean of 34.7 months (range 6-86 months). Nineteen stents were removed for several reasons at a mean of 20.3 months (range 0.25-41 months). These include, exacerbation of autonomic dysreflexic symptoms (n=3); stent migration (n=7); encrustation and stone formation (n=5); incomplete bladder emptying without obstruction (n=3); entrance into fertility program (n=1).The Memokath stent is safe, easy and quick to insert with minimal trauma to the urethra. It is effective in the management of DSD and decreasing the detrusor pressure and residual urine volume in SCI patients. Moreover the ease of its removal in a non-traumatic fashion makes this stent an attractive option when patients are still contemplating the method of bladder management, in those wishing to be involved in fertility program and in recently SCI patients who may recover some manual dexterity to perform clean intermittent self-catheterisation. It must be remembered that this is a temporary stent, as our study clearly shows that the majority are removed within two years of insertion.

Chemokines are a family of low molecular weight (8-10 kDa) pro-inflammatory cytokines, which bind to G-protein coupled receptors. Their primary function is chemoattraction and activation of specific leucocytes in various immuno-inflammatory responses. However, new research suggests that they are key players in cancer being involved in the neoplastic transformation of cells, promotion of aberrant angiogenesis, tumour clonal expansion and growth, passage through the extracellular matrix (ECM), intravasation into blood vessels or lymphatics and the non-random homing of tumour metastasis to specific sites. In view of the increasing significance of chemokines and their receptors in cancers of a variety of types, manipulation of this signalling pathway may be important in the development of new anticancer agents. This review provides an overview of recent research advances in this field and examines the potential therapeutic benefits future developments may bring.

Objective To summarize the urological procedures recorded in Hospital Episodes Statistics (HES, 1998–99) and to examine the accuracy of coding and HES. Materials and methods Data on the 10 commonest urological procedures from the Department of Health website ( www.doh.gov.uk/hes ) were extracted, summarized and presented. Results Urethral catheterization, endoscopic procedures on the bladder, prostate, urethra and ureter (excluding ureteric stone extraction), minor open procedures on the foreskin and the vas, bladder instillation, extracorporeal shockwave lithotripsy and prostatic biopsy are the 10 commonest procedures, according to finished consultant episodes. There is published evidence that the data from coding and HES are not completely accurate. Conclusion This study highlights shortfalls in the HES data (1998–99) which may directly affect the funding of urological services.

The field of minimally invasive surgery (MIS) including traditional laparoscopy, single port surgery, and Robotics, has now taken centre stage in modern clinical practice. With continued evolution in technologies, there is now the need to train the surgeon in a continuous manner. No surgeon is “too” experienced to benefit themselves and the patient.

Enhanced Recovery After Surgery (ERAS) is a multimodal concept combining pre-, peri- and postoperative care evidence based elements aiming to reduce surgical stress. ERAS has been shown to significantly reduce morbidity, length of hospital stay and total costs when applied to colonic surgery. It is therefore considered standard of care in this surgical specialty. Evidence from rectal surgery also suggests that this concept enhance patients recovery. There can be no doubt that ERAS principles have to be applied also in other major pelvic surgeries, such as cystectomy, radical prostatectomy and hysterectomy. However, uncritical application of the guidelines issued from colonic procedures seems inappropriate as the surgical procedures in pelvic cancer surgery differ (e.g. small bowel anastomosis and presence of urine within the peritoneal cavity for cystectomy, longer operative time, increased risk of blood loss). Thus, while there is little doubt that application of some type of ERAS protocols to pelvic cancer surgery will benefit the patients, there is clearly a need for careful adaptation of the many ERAS items for the different types of surgeries.

In recent years, surgical technique for radical retropubic prostatectomy (RRP) has evolved with increasing attention to preservation of anatomic structures and its impact on outcome and quality of life. Technical aspects of nerve-sparing RRP are described. A careful and thorough technique has impact on erectile function and urinary continence and should be performed in all patients. For successful nerve preservation we advocate a lateral approach to the prostate, improvising visualization and simplifying the dissection of the neurovascular bundles from the dorsolateral prostatic capsule. Control of bleeding in the ligation and incision of the Santorini’s plexus ensures the success of the remaining steps. Meticulous apical dissection with preservation of a maximal urethral length and bladder neck are other important factors for the optimal surgery outcomes.

The introduction of laparoscopic technique in pelvic surgery has improved patient outcome and reduced the impact of surgery on the patients’ quality of life. At the same time, the requirements for surgeons have changed profoundly. Traditional surgical training cannot meet the complexity of laparoscopic pelvic surgery and demands of high quality outcome. Simulation training is effective for both basic and advanced laparoscopic skills. There is a need for new training models for surgeons where simulation is an integral part of the training. Clinical training is more efficient when combined with simulation. New concepts of training e.g. mental training have shown great potential to further improve learning curves in combination with simulation.

Technological barriers of telemedicine and surgical telementoring have decreased during recent years, and high-quality videoconference equipment is accessible on a commercial basis. Surgical telementoring has been described as a natural fit in surgery, with solutions demonstrated for laparoscopic and robotic surgery, and mobile telemetering solutions have been demonstrated. Telemedicine is widely used in multidisciplinary teams, assessing pelvic cancer. Evidence exists for cost-effectiveness and safety of telementoring systems, but there is insufficient data for educational outcomes. This chapter focuses on the increasing demand for pelvic cancer surgeons, and how telemedicine can be used to meet societies demand for new surgeons, by improving surgical education and decreasing the obstacles created by distance.

Prostate cancer is the most common cancer and second leading cause of death in men. The evidence base for the diagnosis and treatment of prostate cancer is continually changing. We aim to review and discuss past and contemporary papers on these topics to provoke debate and highlight key dilemmas faced by the urological community. We review key papers on prostate-specific antigen screening, radical prostatectomy versus surveillance strategies, targeted therapies, timing of radiotherapy and alternative anti-androgen therapeutics. Previously, the majority of patients, irrespective of risk, underwent radical open surgical procedures associated with considerable morbidity and mortality. Evidence is emerging that not all prostate cancers are alike and that low-grade disease can be safely managed by surveillance strategies and localized treatment to the prostate. The question remains as to how to accurately stage the disease and ultimately choose which treatment pathway to follow.

Background: The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on penile function after nerve-sparing radical prostatectomy (NSRP) remains unclear. Objective: The primary objective was to compare the efficacy of tadalafil 5 mg once daily and tadalafil 20 mg on demand versus placebo taken over 9 mo in improving unassisted erectile function (EF) following NSRP, as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain (IIEF-EF) score >= 22 after 6-wk drug-free washout (DFW). Secondary measures included IIEF-EF, Sexual Encounter Profile question 3 (SEP-3), and penile length. Design, setting, and participants: Randomised, double-blind, double-dummy, placebocontrolled trial in men = 22, SEP-3, and penile length. Results and limitations: Four hundred twenty-three patients were randomised to tadalafil once daily (n = 139), on demand (n = 143), and placebo (n = 141). The mean age was 57.9 yr of age (standard deviation: 5.58 yr); 20.9%, 16.9%, and 19.1% of patients in the tadalafil once daily, on demand, and placebo groups, respectively, achieved IIEF EF scores >= 22 after DFW; odds ratios for tadalafil once daily and on demand versus placebo were 1.1 (95% confidence interval [CI], 0.6-2.1; p = 0.675) and 0.9 (95% CI, 0.5-1.7; p = 0.704). At the end of double-blind treatment (EDT), least squares (LS) mean IIEF-EF score improvement significantly exceeded the minimally clinically important difference (MCID: DIIEF-EF >= 4) in both tadalafil groups; for SEP-3 (MCID >= 23%), this was the case for tadalafil once daily only. Treatment effects versus placebo were significant for tadalafil once daily only (IIEF-EF: p = 0.016; SEP-3: p = 0.019). In all groups, IIEF-EF and SEP-3 decreased during DFW but continued to improve during open-label treatment. At month 9 (EDT), penile length loss was significantly reduced versus placebo in the tadalafil once daily group only (LS mean difference 4.1 mm; 95% CI, 0.4-7.8; p = 0.032). Conclusions: Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following NSRP, and data suggest a potential role for tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes. Unassisted EF was not improved after cessation of active therapy for 9 mo. (C) 2013 Published by Elsevier B.V. on behalf of European Association of Urology.

Objective To evaluate and assess the long-term complications of using the thermo-expandable, nickel-titanium alloy stent (Memokath™ 051, Engineers & Doctors A/S, Hornbaek, Denmark) for managing benign ureteric strictures. Patients and methods Over a 3-year period, 13 Memokath stents were inserted in 11 patients (mean age 58 years, range 35–85) with 12 lower ureteric strictures. The cause of the stricture was benign in all cases, i.e. radiation fibrosis in three, retroperitoneal fibrosis, ischaemic uretero-ileal anastomosis and scarring after ureteroscopy in two each, and diathermy damage, extraluminal endometriosis and stone passage in one each. Four stents were 9 F with proximal expansion to 17 F and the other nine used were 10.5 F with proximal expansion to 20 F. The patients were followed for a mean (range) of 18 (1.5–33) months. Results No complications or side-effects occurred with nine stents; four stents were removed at a mean (range) of 16.3 (4–33) months. Three of these had become encrusted, two of which had been placed in patients who had either a history of stone disease or recurrent urinary tract infection. The other stent had migrated. Conclusion The Memokath stent appears to have a useful role in managing benign ureteric strictures, but it must be closely monitored in patients who are predisposed to encrustation.

A significant proportion of men undergoing transrectal ultrasound (TRUS) and prostate biopsy report pain during the procedure. A number of different methods of pain relief have been suggested in the literature. We prospectively evaluated the effect of diclofenac suppositories on pain experienced by men undergoing TRUS and prostate biopsy.A prospective, randomized, double-blind, placebo controlled study was performed in 72 patients requiring prostate biopsy. Patients were randomly assigned to receive 100 mg diclofenac or placebo 1 hour prior to the procedure. They were asked to indicate on a 10 cm visual analogue scale the degree of discomfort during the procedure. The patients were then seen 2 weeks later and any morbidity, including infection and bleeding, was assessed.Patients given diclofenac had significantly lower pain scores than those given placebo (2.8 vs 4.9, p0.001). The 2 groups were similar in regard to age, prostate volume, biopsy number, prostate specific antigen, histological diagnosis and complication rate.Rectal administration of diclofenac 1 hour prior to TRUS and prostate biopsy is a simple procedure that significantly relieves the pain experienced with no increase in morbidity. With the trend toward more core samples, screening for prostate cancer and the younger age of patients undergoing biopsy we urge urologists to provide analgesia for this painful procedure.