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OBJECTIVE: To investigate whether poor preoperative cardiopulmonary reserve and comorbid state dictate high-risk status and can predict complications in patients undergoing radical cystectomy (RC). PATIENTS AND METHODS: In all, 105 consecutive patients with transitional cell carcinoma (TCC; stage T1-T3) undergoing robot-assisted (38 patients) or open (67) RC in a single UK centre underwent preoperative cardiopulmonary exercise testing (CPET). Prospective primary outcome variables were all-cause complications and postoperative length of stay (LOS). Binary logistic regression analysis identified potential predictive factor(s) and the predictive accuracy of CPET for all-cause complications was examined using receiver operator characteristic (ROC) curve analysis. Correlations analysis employed Spearman's rank correlation and group comparison, the Mann-Whitney U-test and Fisher's exact test. Any relationships were confirmed using the Mantel-Haenszel common odds ratio estimate, Kaplan-Meier analysis and the chi-squared test. RESULTS: The anaerobic threshold (AT) was negatively (r = -206, P = 0.035), and the ventilatory equivalent for carbon dioxide (VE/VCO₂) positively (r = 0.324, P = 0.001) correlated with complications and LOS. Logistic regression analysis identified low AT ( 50% of patients presenting for RC had significant heart failure, whereas preoperatively only very few (2%) had this diagnosis. Analysis using the Mann-Whitney test showed that a VE/VCO₂ ≥33 was the most significant determinant of LOS (P = 0.004). Kaplan-Meier analysis showed that patients in this group had an additional median LOS of 4 days (P = 0.008). Finally, patients with an American Society of Anesthesiologists grade of 3 (ASA 3) and those on long-term β-blocker therapy were found to be at particular risk of myocardial infarction (MI) and death after RC with odds ratios of 4.0 (95% CI 1.05-15.2; P = 0.042) and 6.3 (95% CI 1.60-24.8; P = 0.008). CONCLUSION: Patients with poor cardiopulmonary reserve and hypertension are at higher risk of postoperative complications and have increased LOS after RC. Heart failure is known to be a significant determinant of perioperative death and is significantly under diagnosed in this patient group

Robotic surgery is becoming more and more commonplace. At the same time, so are complications, especially related to erectile function. The population being diagnosed with cancer is younger, with more aggressive cancers and higher expectations for good erectile function postoperatively. We conduct a retrospective analysis of literature over 20 years for Embase and Medline. Search terms used include (Robotic) AND (prostatectomy) AND (erectile function). There are a variety of multifactorial causes, resulting in worsening ED post-robotic radical prostatectomy; however, there are a number of treatments that can support this. There is much we can do to help prevent patients getting postoperative erectile dysfunction post-radical surgery. However, part of this is management of realistic patient expectations.

Objectives One of the most reliable methods for diagnosing bladder cancer is cystoscopy. Depending on the findings, this may be followed by a referral to a more experienced urologist or a biopsy and histological analysis of suspicious lesion. In this work, we explore whether computer-assisted triage of cystoscopy findings can identify low-risk lesions and reduce the number of referrals or biopsies, associated complications, and costs, although reducing subjectivity of the procedure and indicating when the risk of a lesion being malignant is minimal. Materials and methods Cystoscopy images taken during routine clinical patient evaluation and supported by biopsy were interpreted by an expert clinician. They were further subjected to an automated image analysis developed to best capture cancer characteristics. The images were transformed and divided into segments, using a specialised color segmentation system. After the selection of a set of highly informative features, the segments were separated into 4 classes: healthy, veins, inflammation, and cancerous. The images were then classified as healthy and diseased, using a linear discriminant, the naive Bayes, and the quadratic linear classifiers. Performance of the classifiers was measured by using receiver operation characteristic curves. Results The classification system developed here, with the quadratic classifier, yielded 50% false-positive rate and zero false-negative rate, which means, that no malignant lesions would be missed by this classifier. Conclusions Based on criteria used for assessment of cystoscopy images by medical specialists and features that human visual system is less sensitive to, we developed a computer program that carries out automated analysis of cystoscopy images. Our program could be used as a triage to identify patients who do not require referral or further testing.

Identifying biomarkers and signaling pathways are important for the management of prostate cancer (CaP) radioresistance. In this study, we identified differential proteins and signaling pathways from parental CaP cell lines and CaP radioresistant (RR) sublines using a label-free LC-MS/MS proteomics approach. A total of 309 signaling pathway proteins were identified to be significantly altered between CaP and CaP-RR cells (p ≤ 0.05, fold differences >1.5, ≥80% power). Among these proteins, nineteen are common among three paired CaP cell lines and associated with metastasis, progression and radioresistance. The PI3K/Akt, VEGF and glucose metabolism pathways were identified as the main pathways associated with CaP radioresistance. In addition, the identified potential protein markers were further validated in CaP-RR cell lines and subcutaneous (s.c) animal xenografts by western blotting and immunohistochemistry, respectively and protein aldolase A (ALDOA) was selected for a radiosensitivity study. We found the depletion of ALDOA combined with radiotherapy effectively reduced colony formation, induced more apoptosis and increased radiosensitivity in CaP-RR cells. Our findings indicate that CaP radioresistance is caused by multifactorial traits and downregulation of ALDOA increases radiosensitivity in CaP-RR cells, suggesting that controlling these identified proteins or signaling pathways in combination with radiotherapy may hold promise to overcome CaP radioresistance.

Angiogenesis is required for tumour growth and is induced principally by vascular endothelial growth factor A (VEGF-A). VEGF-A pre-mRNA is alternatively spliced at the terminal exon to produce two families of isoforms, pro- and anti-angiogenic, only the former of which is upregulated in prostate cancer (PCa). In renal epithelial cells and colon cancer cells, the choice of VEGF splice isoforms is controlled by the splicing factor SRSF1, phosphorylated by serine-arginine protein kinase 1 (SRPK1). Immunohistochemistry staining of human samples revealed a significant increase in SRPK1 expression both in prostate intra-epithelial neoplasia lesions as well as malignant adenocarcinoma compared with benign prostate tissue. We therefore tested the hypothesis that the selective upregulation of pro-angiogenic VEGF in PCa may be under the control of SRPK1 activity. A switch in the expression of VEGF165 towards the anti-angiogenic splice isoform, VEGF165b, was seen in PC-3 cells with SRPK1 knockdown (KD). PC-3 SRPK1-KD cells resulted in tumours that grew more slowly in xenografts, with decreased microvessel density. No effect was seen as a result of SRPK1-KD on growth, proliferation, migration and invasion capabilities of PC-3 cells in vitro. Small-molecule inhibitors of SRPK1 switched splicing towards the anti-angiogenic isoform VEGF165b in PC-3 cells and decreased tumour growth when administered intraperitoneally in an orthotopic mouse model of PCa. Our study suggests that modulation of SRPK1 and subsequent inhibition of tumour angiogenesis by regulation of VEGF splicing can alter prostate tumour growth and supports further studies for the use of SRPK1 inhibition as a potential anti-angiogenic therapy in PCa.

Objectives: The proto-oncogene ETS-related gene ( ERG ) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses. Methods: Detection of the TMPRSS2-ERG fusion was done using direct methods (reverse transcription polymerase chain reaction [PCR] and fluorescence in situ hybridization) and indirect methods for ERG mRNA and protein expression using quantitative PCR and immunohistochemistry, respectively. A linear equation method was used to quantitatively determine relative proportions of ERG variants ( ERG72/Δ72 , ERG81/Δ81 ) for each sample. Results: ERG mRNA and protein expression is increased in patients with advanced prostate cancer, with higher levels of ERG expression significantly associated with seminal vesicle invasion (stage pT3b) and biochemical recurrence. Genes involved in cell migration and invasiveness (matrix metalloproteinase 7, osteopontin, and septin 9) are increased in prostate cancers that overexpress ERG . In addition, there is a clear indication of increased retention of exons 10 and 11 in prostate cancer. Conclusions: Analysis of ERG and its variants may be valuable in determining prognosis and development of prostate cancer.

AimsTo assess the lymph node content of anterior prostatic fat (APF) sent routinely at robot-assisted laparoscopic radical prostatectomy (RALP) and the incidence of positive nodes in the extended pelvic lymph node dissection.MethodsBetween September 2008 and April 2012, APF excised from 282 patients who underwent RALP was sent for pathological analysis. This tissue was completely embedded and lymph nodes counted.ResultsIn total, 49/282 (17%) patients had lymph nodes in the APF, median lymph node yield in this tissue was 1 (range 1–5). In four patients, the lymph nodes contained metastatic deposits. These patients did not have positive nodes elsewhere in the extended lymph node dissection.ConclusionsAPF contains lymph nodes in 1 in 6 patients and infrequently these may be malignant. APF should always be removed at radical prostatectomy. APF should be routinely sent for pathological analysis.

261 Background: Miltuximab is a chimeric antibody targeting Glypican-1 which is overexpressed in prostate cancer. Miltuximab has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. Methods: Metastatic patients (prostate, pancreatic and bladder) were dosed with unlabelled Miltuximabfollowed by the infusion of 1 mg/250MBq 67Ga-Miltuximab. Patients underwent whole body gamma and SPECT/CT scans up to 144 hours post-infusion. Standard of care imaging was performed at least 14 days before and after participation. Safety was evaluated by an external monitoring committee. Total organ exposure was determined by dosimetry of whole-body gamma scans. Antibody pharmacokinetics were also determined. Results: 12 patients were enrolled into the trial. Miltuximabwas well tolerated and did not elicit any drug-related adverse reactions. Liver and spleen uptake of 67Ga-Miltuximabwas observed from 30 min to 72 hours post dose. Pre-infusion of unlabelled Miltuximab resulted in reduced liver accumulation and increased distribution in the rest of the body. Miltuximab targeting to sites of active progressive disease was observed in certain prostate cancer patients who had failed enzalutamide treatment. Dosimetry analysis combined with antibody pharmacokinetic data was used to establish safe dose limits for a Phase 1 study. Conclusions: This study is the first in human for Miltuximaband demonstrates its potential for further clinical evaluation as a theranostic in prostate cancers and formed the basis for a Phase I imaging and therapy study planned for 2019. This study will use 89Zr-labelled Miltuximab to screen eligible patients and confirm tumour localisation, followed by treatment with 177Lu-labelled Miltuximab. Clinical trial information: ACTRN12616000787482.

Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P

Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry. One selected glycolysis marker, lactate dehydrogenase A (LDHA) was validated, and further investigated for its role in CaP radioresistance. We found that 378 proteins and 51 pathways were significantly differentially expressed between PC-3RR and PC-3 xenograft tumors, and that the glycolysis pathway is closely linked with CaP radioresistance. In addition, we also demonstrated that knock down of LDHA with siRNA or inhibition of LDHA activity with a LDHA specific inhibitor (FX-11), could sensitize PC-3RR cells to radiotherapy with reduced epithelial-mesenchymal transition, hypoxia, DNA repair ability and autophagy, as well as increased DNA double strand breaks and apoptosis. In summary, we identified a list of potential RR protein markers and important signaling pathways from a PC-3RR xenograft mouse model, and demonstrate that targeting LDHA combined with radiotherapy could increase radiosensitivity in RR CaP cells, suggesting that LDHA is an ideal therapeutic target to develop combination therapy for overcoming CaP radioresistance.

Higher circulating levels of IGF-I have been associated with increased risk of prostate and some other cancers. Most research on prostate cancer has been based on men with symptoms or identified following treatment of benign disease. However, increasing numbers of cancer cases are now detected in asymptomatic men following prostate-specific antigen (PSA) tests. We therefore used a population-based case-finding exercise using the PSA test to examine whether associations between the IGF axis and cancer risk were apparent in this population. A matched case-control study was conducted among 7,383 men (50–70 years) receiving a PSA test as part of a case-finding exercise. Assays of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were performed on cases and 2 controls matched on age, recruitment center and calendar time. Analyses were based on 176 cases and 324 matched controls. The risk of prostate cancer increased across quartiles of IGF-I (highest vs. lowest quartile, OR = 2.34; 95% CI = 1.26–4.34; ptrend = 0.02) and IGF-II (OR = 1.78; 95% CI = 0.94–3.15; ptrend = 0.09). Controlling for smoking history and IGFBP-3 strengthened associations with cancer for both IGF-I (OR = 3.00; 95% CI = 1.50–6.01; ptrend 0.005) and IGF-II (OR = 2.02; 95% CI = 1.07–3.84; ptrend = 0.04) Associations between the IGFs and cancer risk were stronger for advanced cases. Our findings suggest that both IGF-I and IGF-II are associated with an increased risk of screen-detected prostate cancer. © 2003 Wiley-Liss, Inc.

OBJECTIVES: To examine whether measurement of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-2 or IGFBP-3, alone or in combination, enhanced the specificity of prostate cancer detection among men with a prostate-specific antigen (PSA) level of 3 ng/mL or greater beyond that achieved by the free/total PSA index. METHODS: Cross-sectional analysis was performed on blood samples taken from 597 asymptomatic men (79% of those biopsied) participating in a community case-finding exercise. All men had a total PSA level of 3 ng/mL or greater and had undergone prostate biopsy. Assays of IGF-I, IGF-II, IGFBP-2, IGFBP-3, and free and total PSA were performed. The predictive performance of a range of measures was assessed using receiver operating characteristic analyses and compared with the free/total PSA index, for all biopsies and for men with a PSA level of 3 to 10 ng/mL. The overall test performance was summarized using the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 597 men, 185 (31.0%) had prostate cancer identified at biopsy. When all biopsies were included, the performance of the free/total PSA index (AUC 0.73) was significantly greater than for IGF-I (AUC 0.59; P

While multi-fingered robotic hands have been developed for decades, none has been used for surgical operations. µAngelo is an anthropomorphic master-slave system for teleoperated robot-assisted surgery. As part of this system, this paper focuses on its slave instrument, a miniature three-digit hand. The design of the mechanism of such a manipulator poses a challenge due to the required miniaturization and the many active degrees of freedom. As the instrument has a human-centered design, its relation to the human hand is discussed. Two ways of routing its cable-driven mechanism are investigated and the method of deriving the input-output functions that drive the mechanism is presented.

Robotic cystectomy to this day, remains the hardest operation a surgeon has to do. Additionally, there is no guarantee, that what is done robotically, this will enable a lack of complications compared to open surgery. This chapter covers robotic management of ureteric strictures.

Paolo Gontero*, Giancarlo Marra, Paolo Alessio, Marco Oderda, Anna Palazzetti, Francesca Pisano, Antonino Battaglia, Stefania Munegato, Claudia Filippini, Bruno Frea, Turin, Italy; Fernando Munoz, Aosta, Italy; Estefania Linares, Raphael Sanchez Salas, Paris, France; Sanchia Goonewardene, Prokar Dasgupta, Declan Cahill, Ben Challacombe, London, United Kingdom; David Gillatt, Raj Persad, Bristol, United Kingdom; Juan Palou, Barcelona, Spain; Steven Joniau, Leuven, Belgium; Salvatore Smelzo, Thierry Piechaud, Bordeaux, France; Alexandre De La Taille, Cr eteil, France; Morgan Roupret, Paris, France; Derya Tilki, Hamburg, Germany; Rick Popert, London, United Kingdom

Background: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. Methods/design: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). Discussion: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

Study Type – Symptom prevalence (prospective cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Case series have described lower urinary tract symptoms associated with ketamine use including severe pain, frequency, haematuria and dysuria. Little is known regarding the frequency of symptoms, relationship of symptoms with dose and frequency of use and natural history of symptoms once the ketamine user has stopped. This study describes the prevalence of ketamine use in a population of recreational drug users in a dance music setting. It shows a dose–frequency relationship with ketamine use. It shows that urinary symptoms associated with recreational ketamine use may lead to a considerable demand on health resources in the primary-, secondary- and emergency-care settings. It shows that symptoms may improve once ketamine use is decreased. OBJECTIVE • To investigate the prevalence and natural history of urinary symptoms in a cohort of recreational ketamine users. PATIENTS AND METHODS • A purposeful sampling technique was used. • Between November 2009 and January 2010 participants were invited to undertake an on-line questionnaire promoted by a national dance music magazine and website. • Data regarding demographics and illicit drug-use were collected. • Among respondents reporting recent ketamine use, additional information detailing their ketamine use, experience of urinary symptoms and use of related healthcare services was obtained. RESULTS • In all, 3806 surveys were completed, of which 1285 (33.8%) participants reported ketamine use within the last year. • Of the ketamine users, 17% were found to be dependent on the drug; 26.6% (340) of recent ketamine users reported experiencing urinary symptoms. • Urinary symptoms were significantly related to both dose of ketamine used and frequency of ketamine use. • Of 251 users reporting their experience of symptoms over time in relationship to their use of ketamine, 51% reported improvement in urinary symptoms upon cessation of use with only eight (3.8%) reporting deterioration after stopping use. CONCLUSIONS • Urinary tract symptoms are reported in over a quarter of regular ketamine users. • A dose and frequency response relationship has been shown between ketamine use and urinary symptoms. • Both users and primary-care providers need to be educated about urinary symptoms that may arise in ketamine users. A multi-disciplinary approach promoting harm reduction, cessation and early referral is needed to manage individuals with ketamine-associated urinary tract symptoms to avoid progression to severe and irreversible urological pathologies.

Background: The development of androgen independence, chemo-, and radioresistance are critical markers of prostate cancer progression and the predominant reasons for its high mortality. Understanding the resistance to therapy could aid the development of more effective treatments. Aim: The aim of this study is to investigate the effects of insulin-like growth factor-binding protein-2 (IGFBP-2) on prostate cancer cell proliferation and its effects on the response to docetaxel. Methods: DU145 and PC3 cells were treated with IGFBP-2, insulin-like growth factor I (IGF-I) alone or in combination with blockade of the IGF-I receptor or integrin receptors. Cells were also treated with IGFBP-2 short interfering ribonucleic acid with or without a PTEN (phosphatase and tensin homologue deleted on chromosome 10) inhibitor or docetaxel. Tritiated thymidine incorporation was used to measure cell proliferation and Trypan blue cell counting for cell death. Levels of IGFBP-2 mRNA were measured using RT–PCR. Abundance and phosphorylation of proteins were assessed using western immunoblotting. Results: The IGFBP-2 promoted cell growth in both cell lines but with PC3 cells this was in an IGF-dependent manner, whereas with DU145 cells the effect was independent of IGF receptor activation. This IGF-independent effect of IGFBP-2 was mediated by interaction with β-1-containing integrins and a consequent increase in PTEN phosphorylation. We also determined that silencing IGFBP-2 in both cell lines increased the sensitivity of the cells to docetaxel. Conclusion: The IGFBP-2 has a key role in the growth of prostate cancer cells, and silencing IGFBP-2 expression reduced the resistance of these cells to docetaxel. Targeting IGFBP-2 may increase the efficacy of docetaxel.

Ketamine has become increasingly recognized as a drug of recreational use. Individuals using significant amounts have developed symptoms including a small painful bladder, ureteric obstruction, papillary necrosis and hepatic dysfunction. The present paper examines the current literature on the relationship between ketamine use and these symptoms. Our own clinical experience and the data available clarify the causal relationship, and further data help to elucidate the mechanism of damage. On the basis of continued work and development with patients who are ketamine users we suggest an assessment and treatment regime that includes cessation of ketamine use and adequate analgesia to overcome symptoms. In conclusion, it is important for medical practitioners who encounter patients with these symptoms to ask about recreational drug use. Ketamine remains a safe and effective drug to use under appropriate medical supervision. Patients identified as suffering from this syndrome will need to be referred to a urological unit with an interest in the treatment of the condition.

Various conflicting guidelines and recommendations about prostate cancer screening and early detection have left both clinicians and their patients quite confused. At the Prostate Cancer World Congress held in Melbourne in August 2013, a multidisciplinary group of the world's leading experts in this area gathered together and generated this set of consensus statements to bring some clarity to this confusion. The five consensus statements provide clear guidance for clinicians counselling their patients about the early detection of prostate cancer.

Introduction: Enhanced recovery protocols (ERPs) aim to improve outcome following major abdominal surgery. Our ERP for radical cystectomy focuses on reduced bowel preparation and standardised feeding and analgesic regimens. Although the ERP safely decreased hospital stay, time to return of bowel function has not been affected. The current study aims to assess the addition of chewing gum on return of bowel function as part of an ERP. Patients and methods: We examined the addition of chewing gum to our ERP. Data was obtained retrospectively from 112 consecutive patients, 56 before and 56 after implementing chewing gum in to the EPR. The primary outcome measured was return of bowel function signified by first defecation after surgery. Results: The demographics of the two groups showed no significant difference in age, gender distribution, American Society of Anesthesiologists grade, or type of urinary diversion. A significant reduction in the time to return of bowel function was observed in patients using chewing gum post-operatively (4 versus 6 days, p < 0.0001). The median inpatient stay was 13 days in both groups; however there was a trend to an earlier discharge in those patients receiving chewing gum. Conclusion: The introduction of chewing gum to our ERP is associated with a faster return of bowel function and may lead to a reduced inpatient stay.

Study Type – Therapy (outcomes research) Level of Evidence 2c OBJECTIVE To assess the patterns of care for low-risk localized prostate cancer. Management of this condition is highly controversial, with a range of treatment options, but there are no published UK data. METHODS Data from the British Association of Urological Surgeons (BAUS) Cancer Registry were linked to the UK Association of Cancer registries postcode directory. The demographic and clinical characteristics, and the initial management of men diagnosed with low-risk localized prostate cancer in the UK between 2000 and 2006 were analysed. RESULTS In all, 43 322 cases of localized prostate cancer were recorded in the BAUS Registry between 2000 and 2006, of which 8861 (20%) met the criteria for low-risk disease. The proportion classified as low risk ranged from 16% in 2000 to 21% in 2006. The proportion of men with low-risk disease opting for ‘watchful waiting’ increased from 0% to 39% over the same period. Treatment choice was associated with socio-economic status. For example, radical prostatectomy was chosen by 34% of patients in the most affluent quintile, compared with 19% in the most deprived quintile (P= 0.01). CONCLUSION The management of low-risk localized prostate cancer in the UK has changed markedly in recent years, and contrasts with that in the USA. The association observed between socio-economic status and choice of treatment deserves further study.

A substantial proportion of patients who have undergone a radical prostatectomy for localised prostate cancer will have either persistently detectable prostate-specific antigen (PSA) levels or a delayed rise in PSA. The optimum treatment for these situations is not known. The key question is whether the PSA is reflective of local or distant progression. For salvage radiotherapy to be most effective, treatment should be considered before the PSA level is allowed to rise too high, when disease is more likely to be confined to the prostate bed. However, at low PSA levels, current imaging techniques are poor at detecting disease, making it difficult to differentiate local and distant recurrences and to target the radiotherapy appropriately. We review current and investigational imaging techniques, including bone scan, computed tomography, magnetic resonance imaging, positron emission tomography and Prostascint, assessing their utility in the situation of biochemical recurrence after radical prostatectomy.

Background: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status. Methods: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received. Results: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15–1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05–1.80). The Delphi analysis did not suggest differential management by ethnicity. Conclusions: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men.

Black men in England have three times the age-adjusted incidence of diagnosed prostate cancer as compared with their White counterparts. This population-based retrospective cohort study is the first UK-based investigation of whether access to diagnostic services underlies the association between race and prostate cancer. Prostate cancer was ascertained using multiple sources including hospital records. Race and factors that may influence prostate cancer diagnosis were assessed by questionnaire and hospital records review. We found that Black men were diagnosed an average of 5.1 years younger as compared with White men (P

Objective To evaluate p53 and bcl-2 immunohistochemistry in preoperative biopsies and radical prostatectomy specimens, as predictors of biochemical recurrence. Patients and methods Preoperative biopsies from 73 men, and the radical prostatectomies from these men and from a further 47 men, were evaluated. The serum prostate specific antigen (PSA) level, Gleason score, pathological stage and margin involvement were recorded. The immunohistochemical expression of p53 and bcl-2 was studied on a representative area of tumour with the highest Gleason grade. The median follow-up was 53 months. Results During the follow-up 47 of the 120 patients had a biochemical recurrence. Capsular penetration was present in 63 (53%) and the surgical margins were positive in 47 (39%). The Gleason score was

Item does not contain fulltext Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGFxxxb, where xxx is the amino acid number. The most studied isoforms, VEGF165 and VEGF165b have been shown to be present in tumour and normal tissues respectively. VEGF165b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF165b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF165b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF165b can inhibit growth of multiple tumour types in vivo indicating that VEGF165b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF165b expression by regulation of splicing, overexpression of VEGF165b, or therapeutic delivery of VEGF165b to tumours.

It is known that African American men have a greater risk of prostate cancer than white men. We investigated whether this was true for first-generation black Caribbean and black African men in the United Kingdom.A clinical cohort study design recruiting all cases of prostate cancer diagnosed over a 5-yr period and residing in defined areas of London and Bristol. We calculated the age-standardised incidence rates and relative risk for all black men, and black Caribbean and black African men versus white men.Black men had higher age-adjusted rates of prostate cancer (166 per 100,000, 95% confidence interval [95%CI], 151-180 per 100,000) than white men (56.4 per 100,000, 95%CI, 53.3-59.5 per 100,000). The relative risks for all black, black Caribbean, and black African men were 3.09 (95%CI, 2.79-3.43; p0.0001), 3.19 (95%CI, 2.85-3.56; p0.0001) and 2.87 (95%CI, 2.34-3.53; p0.0001), respectively. There was no strong evidence that the rates for black Caribbean differed from black African men. The higher risk in black men compared with white men was more apparent in younger age groups (p value for interaction0.001).Black men in the United Kingdom have substantially greater risk of developing prostate cancer compared with white men, although this risk is lower than that of black men in the United States. The similar rates in black Caribbean and black African men suggest a common genetic aetiology, although migration may be associated with an increased risk attributable to a gene-environment interaction.

A significant proportion of patients with prostate cancer experience biochemical failure following primary therapy. Of these, some may be at high risk of dying from prostate cancer. Salvage therapy can improve survival outcomes in these patients but at the cost of adverse effects that may affect quality of life. The choice of salvage therapy depends on the location of the tumour recurrence and how aggressive the disease is. This article examines the treatment options for patients with a rising prostate-specific antigen (PSA) level after radical prostatectomy or radiotherapy, using two clinical scenarios. After radical prostatectomy fails, radiotherapy is a salvage option for low-risk patients with local disease recurrence; however, hormonal therapy, with or without radiotherapy, may represent a better option for patients with high-risk disease. Local salvage therapy options in patients with PSA failure after radiotherapy include brachytherapy, cryotherapy, high-intensity focused ultrasound, and surgery. In patients with moderate- to high-risk disease, most clinicians would also prescribe some form of hormonal treatment.

Bilateral orchiectomy became the "gold standard" treatment option for advanced prostate cancer following the Nobel Prize winning study by Huggins and Hodges in 1941. Almost 40 yr later, the combination of a nonsteroidal antiandrogen with castration-based treatment (combined androgen blockade [CAB]) was proposed to offer superior response and survival compared with castration alone. However, 25 yr and many randomised studies later, the benefit of CAB remains controversial. Here, we present a clinical scenario that describes a patient with advanced prostate cancer and we review the available treatment options. The first part of the article focuses on androgen-dependent disease, comparing castration (surgical or medical) to either Casodex™ (bicalutamide) 150mg monotherapy or CAB. In the CAB setting, Casodex 50mg combined with castration-based therapy is calculated to reduce the rate of all-cause mortality by an estimated 20% compared with castration alone. The second part of the article describes treatment options for androgen-independent prostate cancer, including alternative forms of hormonal therapy, such as oestrogen therapy and ketoconazole- and docetaxel-based chemotherapy.

Prostate cancer is the third most common cause of male death in Europe. In 2004, prostate cancer accounted for 85,200 deaths, equating to 8.9% of all male cancer deaths. In recent years, heightened awareness of the disease and increased prostate-specific antigen screening have resulted in an overall rise in the incidence of prostate cancer detection, with more young men presenting with earlier stage (ie, localised or locally advanced) disease. For many patients diagnosed with prostate cancer, especially for those who wish to maintain an active life, quality of life is of paramount importance. The challenge, therefore, is to identify which patients will benefit most from the different treatment options available. In this article we present two clinical scenarios to facilitate discussion of the treatment options available for two patients—one with localised disease and another with asymptomatic locally advanced disease—who are both anxious to avoid death from prostate cancer.

To determine the contemporary survival outcomes from a whole population and identify significant predictors of survival, as contemporary population-based survival outcomes after radical cystectomy (RC) for the treatment of bladder cancer (BC) are sparse. Reports suggest a large disparity between population outcomes and those of centres of excellence.All invasive BC cases diagnosed between 2001 and 2007 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. All patients who underwent RC between 2001 and 2009 were selected for this study (804 patients). Follow-up was to the end of 2009. Outcomes assessed were disease-specific survival (DSS) and overall survival (OS). Multivariable Cox regression and log-rank analysis were used to model and compare survival within groups.Of 804 patients diagnosed during the study period 420 (52.2%) died during follow-up. The 5-year DSS and OS for all patients was 59.6% and 53.2%, respectively. The 5-year DSS for patients with localised, regional and distant disease, undergoing RC was 72%, 51% and 10%, respectively. Age (P0.001) and stage (P0.001) were associated with 5-year DSS and OS after adjusting for all other variables. High-volume centres had significantly better 5-year DSS compared with low-volume centres (P0.05). The 30-day mortality for high- vs low-volume centres was 1.8% and 3.6%, respectively. Perioperative mortality improved over time for high- and moderate-volume centres but not for low-volume centres.Contemporary survival outcomes after RC are much improved compared with older studies and appear close to results from academic centres of excellence. High-volume centres report better 5-year DSS outcomes than lower volume centres.

Radiotherapy (RT) is one of the most important strategies in cancer treatment. Radioresistance is a major challenge to RT and results in locoregional recurrence and metastasis. Thus, there is a great interest in investigating biomarkers to distinguish radiosensitive from radioresistant (RR) cancer patients. The development of proteomic techniques has sparked new searches for novel proteins for cancer biomarker discovery. Modern proteomic techniques allow for a high-throughput analysis of samples with the visualization and quantification of thousands of potential protein and peptide markers. The discovery of RR biomarkers can provide a clue for predicting RT response and discover therapeutic targets for developing personalised medicine of individual patients. In the past decade, emerging advanced proteomic technologies have been performed to identify radiation-related biomarkers in human cancers. This review discusses the mass spectrometry (MS)-based proteomic techniques in RR cancer biomarker discovery, summarises RR biomarkers identified in cancers from proteomics-based findings and explores potential values of RR biomarkers for future clinical trials.

OBJECTIVESTo describe national trends in the practice of radical nephrectomy (RN) in England between 1995 and 2002.METHODSData were extracted from the Hospital Episode Statistics database of the Department of Health in England between 1995/1996 and 2001/2002. Patients were included in the study if an International Classification of Diseases diagnosis code (ICD-10) for malignant neoplasm of the kidney, renal pelvis or ureter, and an operative procedure code (OPCS-4) describing total or partial excision of the kidney by either a laparoscopic or open approach, were present in any of the diagnosis or operative procedure fields. Overall, 17 308 patients were included.RESULTSPatient age and the proportion who were men did not change over the study period. The proportion of patients admitted as an emergency decreased from 14.0% to 7.5% over this period (P < 0.001). The mean waiting duration increased by almost 6 days (P < 0.001) and length of stay by approximate to 1 day, from 11.7 days in 1995 to 10.8 days in 2001 (P < 0.001). In-hospital mortality decreased from 2% to 1.5% (P = 0.134). In-hospital mortality and length of stay were higher in older patients and in those admitted as an emergency. Women had a longer stay than men (11.5 vs 11.1 days), but in-hospital mortality was higher in men (2.3% vs 1.6%). The national number of RNs per year increased by approximate to 20%, from 2254 in 1995 to 2671 in 2001. Over the same period the mean annual hospital volume of RN increased by approximate to 40%, from 17 in 1995 to 24 in 2001. The annual number of laparoscopic RNs nationally increased from seven in 1995 to 84 in 2002.CONCLUSIONSThe annual number of RNs in England increased by almost a fifth and this was accompanied by an increase in annual hospital volume of about two-fifths. There was a large proportional increase in the number of laparoscopic RNs. Emergency admission rates and length of stay decreased but this was not accompanied by a significant change in in-hospital mortality rate.

UNLABELLED Increasing numbers of men are being diagnosed with prostate cancer and undergo operative curative treatment. It has been suggested that outcome after radical prostatectomy (RP) may vary for different age groups. OBJECTIVE To investigate whether PSA recurrence-free survival after RP is related to age at operation for a cohort of English men. METHODS A total of 854 patients notes from four Urology units were audited for preoperative staging parameters and follow-up data obtained. The relationship of PSA, age, biopsy Gleason grade, clinical stage, era and institution on PSA recurrence-free survival was competitively assessed with a multivariate model. RESULTS Only preoperative PSA (P

OBJECTIVES To describe temporal changes in patient characteristics and outcomes for radical cystectomy (RC) in England between 1995 and 2002, using routinely collected administrative data. PATIENTS AND METHODS Data were extracted from the Hospital Episode Statistics database of the Department of Health in England, describing all patients recorded as having undergone RC between 1995/1996 and 2001/2002; 8228 patients were included. RESULTS Of the patients who had undergone RC, two-thirds were ≥ 65 years old and 75.6% were men. From 1995/1996 to 2001/2002 the annual number of RCs increased from 1013 to 1254, the proportion of patients admitted as an emergency decreased from 6.5% to 4.9%, the mean length of hospital stay decreased from 20.7 days to 18.7 days, and in-hospital mortality rates fell from 5.3% to 3.6%. The length of hospital stay and in-hospital mortality rates were higher in older patients, in female patients, and in those admitted as an emergency. CONCLUSIONS There was no sign of centralization of RCs over the study period, as the 25% increase in annual hospital volume was accompanied by a similar increase in the annual number of RCs. Length of hospital stay and in-hospital mortality rates have decreased.

Objective: To evaluate the efficacy of bicalutamide vs cyproterone acetate in preventing PSA flare (as a surrogate for tumour flare) for patients requiring luteinizing hormone-releasing hormone (LHRH) analogue therapy for prostate cancer. Patients and Methods: In this pilot study, 40 men were randomized 1 : 1 to bicalutamide 50 mg o.d. or cyproterone acetate 100 mg t.i.d. 5 days prior to goserelin acetate and continued for 21 days thereafter. PSA, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were obtained before treatment and on days 6, 8, 10, 16, 21 and 28. Primary end point was PSA. Hormone profile and clinical features including urinary symptoms and bone pain were secondary end points. Results: Both groups were equally matched apart from serum creatinine and ALP. The speed and magnitude of the percentage change in median PSA from baseline was increased for the CPA group but there was no statistically significant difference in the two groups. Although those receiving bicalutamide all showed a testosterone peak, this remained within the normal range. No difference in the frequency of drug-specific adverse events was found. None of the patients died or developed cord compression during the study period. Conclusion: Bicalutamide is able to suppress the initial PSA surge as effectively as cyproterone acetate albeit slightly delayed. A statement whether bicalutamide is equally good at preventing clinical flare cannot be made and should be assessed in an appropriately powered study.

We performed a systematic review and critique of the literature of the relationship between hospital or surgeon volume and health outcomes in patients undergoing radical surgery for cancer of the bladder, kidney or prostate.Four electronic databases were searched to identify studies that describe the relationship between hospital or surgeon volume and health outcomes.All included studies were performed in North America. A total of 12 studies were found that related hospital volume to outcomes. For radical prostatectomy and cystectomy all 8 included studies showed improvement in at least 1 outcome measure with increasing volume and never deterioration. For nephrectomy the 4 included studies produced conflicting results. Four studies were found that related surgeon volume to outcomes. All radical prostatectomy and cystectomy studies showed that some outcomes were better with higher surgeon volume and never deterioration. We did not find any studies of the effect of surgeon volume on outcomes after nephrectomy. The 3 studies of the combined effect of hospital and surgeon volume on outcomes after radical prostatectomy or cystectomy suggest that high volume hospitals have better outcomes, in part because of the effect of surgeon volume and vice versa.Outcomes after radical prostatectomy and cystectomy are on average likely to be better if these procedures are performed by and at high volume providers. For radical nephrectomy the evidence is unclear. The impact of volume based policies (increasing volume to improve outcomes) depends on the extent to which "practice makes perfect" explains the observed results. Further studies should explicitly address selective referral and confounding as alternative explanations. Longitudinal studies should be performed to evaluate the impact of volume based policies.

Growth of new blood vessels (angiogenesis), required for all tumor growth, is stimulated by the expression of vascular endothelial growth factor (VEGF). VEGF is up-regulated in all known solid tumors but also in atherosclerosis, diabetic retinopathy, arthritis, and many other conditions. Conventional VEGF isoforms have been universally described as proangiogenic cytokines. Here, we show that an endogenous splice variant, VEGF165b, is expressed as protein in normal cells and tissues and is circulating in human plasma. We also present evidence for a sister family of presumably inhibitory splice variants. Moreover, these isoforms are down-regulated in prostate cancer. We also show that VEGF165b binds VEGF receptor 2 with the same affinity as VEGF165 but does not activate it or stimulate downstream signaling pathways. Moreover, it prevents VEGF165-mediated VEGF receptor 2 phosphorylation and signaling in cultured cells. Furthermore, we show, with two different in vivo angiogenesis models, that VEGF165b is not angiogenic and that it inhibits VEGF165-mediated angiogenesis in rabbit cornea and rat mesentery. Finally, we show that VEGF165b expressing tumors grow significantly more slowly than VEGF165-expressing tumors, indicating that a switch in splicing from VEGF165 to VEGF165b can inhibit tumor growth. These results suggest that regulation of VEGF splicing may be a critical switch from an antiangiogenic to a proangiogenic phenotype.

Despite a significant increase of the number of radical prostatectomies (RPs) to treat organ-confined prostate cancer, there is very limited documentation of its oncological outcome in the UK. Pathological stage distribution and changes of outcome have not been audited on a consistent basis. We present the results of a multicentre review of postoperative predictive variables and prostatic-specific antigen (PSA) recurrence after RP for clinically organ-confined disease. In all, 854 patient's notes were audited for staging parameters and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment as well as patients with incomplete data and follow-up were excluded. Median follow-up was 52 months for the remaining 705 patients. The median PSA was 10 ng ml−1. A large migration towards lower PSA and stage was seen. This translated into improved PSA survival rates. Overall Kaplan–Meier PSA recurrence-free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA recurrence-free survival probability for PSA ranges 20 ng ml−1 was 0.82, 0.73, 0.59 and 0.20, respectively (log rank, P

OBJECTIVE To determine minimum threshold levels of activity set by surgeons for urological cancer surgery, and to relate threshold levels to stated current procedural volume. METHODS In all, 307 consultant urological surgeons were sent a questionnaire asking them to state for four urological cancer operations of different complexity their current procedural volume; whether minimum volume thresholds per surgeon should be implemented; and if so, the level of such thresholds; 212 (69%) replied. RESULTS For all four procedures >/= 75% of surgeons advocated the setting of a minimum volume threshold. Overall, surgeons set the highest thresholds for radical prostatectomy and the lowest for radical cystectomy with continent diversion. There was no significant association between either the principle of supporting minimum volume thresholds or the level of such a threshold and the number of years worked as a consultant surgeon. The level of surgeon-derived minimum thresholds increased with increasing surgeon procedural volume. CONCLUSION Most surgeons supported the principle of setting minimum volume thresholds. These thresholds appear to be influenced by current procedural volume and by procedural complexity. By setting thresholds greater than their current volume, some surgeons implicitly indicate that their current volume is insufficient to maintain their surgical competency.

OBJECTIVES To report an audit of preoperative staging variables, case selection, stage migration and prostate-specific antigen (PSA) recurrence at five large centres in the south of England. To establish PSA outcome values after radical prostatectomy for clinically localized prostate cancer in the UK, and enable appropriate patient counselling. PATIENTS AND METHODS The notes of 854 patients were audited for preoperative staging variables and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment, and with incomplete data and follow-up, were excluded. RESULTS The median follow-up was 52 months for the remaining 663 patients; the median PSA level was 10 ng/mL. There was a large migration towards lower PSA and stage; this translated into improved PSA survival rates. The overall Kaplan-Meier PSA recurrence-free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA recurrence-free survival probabilities for PSA levels of 20 ng/mL were 0.82, 0.73, 0.59 and 0.20, respectively (Wilcoxon, P

OBJECTIVES To assess the prediction of prostate cancer using extended-field prostatic biopsies (8–11 cores), as such biopsy protocols are recommended to increase the detection of prostate cancer, and as fewer cancers are missed this should improve the prediction of biopsy outcome from the patients’ history, transrectal ultrasonography (TRUS) and serum markers. PATIENTS AND METHODS In all, 260 patients were prospectively evaluated and 206 with a total prostate-specific antigen (PSA) level of

Objectives: To review the evidence underlying the diagnosis, pathology and treatment of lymphoedema of the lower extremities and genitalia from or following the treatment for urological cancer, and to suggest possible underlying pathophysiological mechanisms that may explain its development. Methods: Reviews of the epidemiological, surgical, and scientific literature and personal experience of treatment of patients are used to build a picture of clinical setting and the physiological principles underlying lymphoedema of the leg. Results: Lymphoedema of the leg and genitals results in serious morbidity for the patient. The incidence is largely unknown, but varies according to the type and location of tumours and may be up to 50% in advanced stages of penile carcinoma, or following its treatment. Although the aetiology of the condition is either iatrogenic, or associated with malignancy, the underlying pathophysiology is not well understood. Conclusions: Recent studies in breast cancer related lymphoedema point to underlying vascular as well as lymphatic problems, but the parallels with lower limb lymphoedema are not known.