BackgroundBladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity.ResultsWe defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort (n = 274, non-cancer (n = 167) and bladder cancer (n = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine.ConclusionsEpigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0303-5) contains supplementary material, which is available to authorized users.

What ' s known on the subject? and What does the study add? Suprasacral spinal cord injuries can result in intractable detrusor overactivity adversely effecting patients ' quality of life. It can lead to high pressure bladder resulting in urinary incontinence and deterioration of upper tract function. Augmentation cystoplasty is an accepted procedure in treating refractory neurogenic detrusor overactivity.Several publications have reported on the short-to intermediate-term outcomes with augmentation cystoplasty in patients with spinal cord injury. However, it is not known how these outcomes alter over a longer period. This study has a follow-up of at least 10 years. It evaluates the durability of this procedure over the longer term. It also assesses the patients reported outcome over this period. This data can help counsel patients better when considering augmentation cystoplasty as a treatment option for the management of refractory neurogenic detrusor overactivity secondary to spinal cord injury. OBJECTIVE• To report the long-term outcomes of augmentation ileocystoplasty (AIC) in patients with spinal cord injury (SCI), with a minimum follow-up period of 10 years. PATIENTS AND METHODS• We retrospectively analysed all operations performed by a single surgeon at a specialist spinal unit.• Outcomes were measured by comparing preoperative and follow-up videocystometrograms (VCMGs).• Complications were identifi ed from case notes and the surgery database.• Subjective assessment was through a previously validated questionnaire. RESULTS• The mean (range) follow-up was 14.7 (10.5 -20.3) years. There were 19 patients (12 males) with a mean (range) age at time of surgery of 28.9 (12 -52) years. The mean (range) period from injury to surgery was 4.5 (0.3 -22) years. All had suprasacral injuries.• The VCMGs showed a signifi cant improvement in bladder capacity and a decrease in intravesical pressures ( P < 0.001).• Long-term complications included bladder stones ( n = 4); urosepsis ( n = 2); vesico-ureteric refl ux ( [ VUR ] n = 2), VUR requiring ureteric re-implantation ( n = 1); neurogenic detrusor overactivity ( [ NDO ] n = 1); and laparatomy for bowel obstruction ( n = 1). Surveillance cystoscopies did not detect any bladder neoplasms.• The response rate for the questionnaire survey was 14/17; 13/14 patients were satisfi ed with the operation such that they would consider it again or recommend it to a friend. No patient reported any signifi cant changes in either bowel habit or sexual function. CONCLUSIONS• We found that AIC has excellent long-term outcomes in the defi nitive management of refractory NDO in patients with SCI.• The complications of AIC appear to be more than counterbalanced by a high level of patient satisfaction with the procedure and by the achievement of the primary aim of ensuring continence and upper tract safety in these patients. KEYWORDSspinal cord injury , ileocystoplasty , augmentation cystoplasty Study Type -Therapy (case series) Level of Evidence 4

The aim of this study was to test the utility of AIMP3, an upstream regulator of DNA damage response following genotoxic stress, as a clinical biomarker in muscle-invasive bladder cancer (MIBC). AIMP3 was identified from a meta-analysis of a global gene-expression dataset. AIMP3 protein expression was determined by immunohistochemistry on a customised bladder cancer tissue-microarray (TMA). The mechanism of gene silencing was probed using methylation-specific PCR. The association between AIMP3 expression, Tp53 transactivity and genomic stability was analysed. In vitro AIMP3 translocation to the nucleus in response to ionising radiation was demonstrated using immunofluorescence. Radiosensitisation effects of siRNA-mediated AIMP3-knockdown were measured using colony forming assays. TMAs derived from patients enrolled in BCON, a Phase III multicentre radiotherapy trial in bladder cancer (ISRCTN45938399) were used to evaluate the association between AIMP3 expression and survival. The prognostic value of AIMP3 expression was determined in a TMA derived from patients treated by radical cystectomy. Loss of AIMP3 expression was frequent in MIBC and associated with impaired Tp53 transactivity and genomic instability. AIMP3-knockdown was associated with an increase in radioresistance. Loss of AIMP3 expression was associated with survival in MIBC patients following radiotherapy (HR = 0.53; 95% CI: 0.36 to 0.78, p = 0.002) but was not prognostic in the cystectomy set. In conclusion, AIMP3 expression is lost in a subset of bladder cancers and is significantly predictive of survival following radiotherapy in MIBC patients.

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BackgroundFocal therapy is being offered as a viable alternative for men with localised prostate cancer (PCa), but it is unclear which men may be suitable.ObjectiveTo determine the proportion of men with localised PCa who are potentially suitable for focal therapy.Design, setting, and participantsOur institutional transperineal template prostate-mapping (TTPM) biopsy registry of 377 men from 2006 to 2010 identified 291 consecutive men with no prior treatment.InterventionTTPM biopsies using a 5-mm sampling frame.Outcome measurements and statistical analysisSuitability for focal therapy required the cancer to be (1) unifocal, (2) unilateral, (3) bilateral/bifocal with at least one neurovascular bundle avoided, or (4) bilateral/multifocal with one dominant index lesion and secondary lesions with Gleason ≤3 + 3 and cancer core involvement ≤3 mm. Binary logistic regression modelling was used to determine variables predictive for focal therapy suitability.Results and limitationsThe median age was 61 yr, and the median prostate-specific antigen was 6.8 ng/ml. The median total was 29 cores, with a median of 8 positive cores. Of 239 of 291 men with cancer, 29% (70 men), 60% (144 men), and 8% (20 men) had low-, intermediate-, and high-risk PCa, respectively. Ninety-two percent (220 men) were suitable for one form of focal therapy: hemiablation (22%, 53 men), unifocal ablation (31%, 73 men), bilateral/bifocal ablation (14%, 33 men), and index lesion ablation (26%, 61 men). Binary logistic regression modelling incorporating transrectal biopsy parameters showed no statistically significant predictive variable. When incorporating TTPM parameters, only T stage was a significant negative predictor for suitability (p = 0.001) (odds ratio: 0.001 [95% confidence interval, 0.000–0.048]). Limitations of the study include potential selection bias caused by tertiary referral practise and lack of long-term results on focal therapy efficacy.ConclusionsFocal therapy requires an accurate tool to localise individual cancer lesions. When such a test, TTPM biopsy, was applied to men with low- and intermediate-risk PCa, most of the men were suitable for a tissue preservation strategy.

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Objective To conduct a multi‐institutional validation of a high‐fidelity, perfused, inanimate, simulation platform for robot‐assisted partial nephrectomy (RAPN) using incorporated clinically relevant objective metrics of simulation (CROMS), applying modern validity standards. Materials and Methods Using a combination of three‐dimensional (3D) printing and hydrogel casting, a RAPN model was developed from the computed tomography scan of a patient with a 4.2‐cm, upper‐pole renal tumour (RENAL nephrometry score 7×). 3D‐printed casts designed from the patient’s imaging were used to fabricate and register hydrogel (polyvinyl alcohol) components of the kidney, including the vascular and pelvicalyceal systems. After mechanical and anatomical verification of the kidney phantom, it was surrounded by other relevant hydrogel organs and placed in a laparoscopic trainer. Twenty‐seven novice and 16 expert urologists, categorized according to caseload, from five academic institutions completed the simulation. Results Clinically relevant objective metrics of simulators, operative complications, and objective performance ratings (Global Evaluative Assessment of Robotic Skills [GEARS]) were compared between groups using Wilcoxon rank‐sum (continuous variables) and parametric chi‐squared (categorical variables) tests. Pearson and point‐biserial correlation coefficients were used to correlate GEARS scores to each CROMS variable. Post‐simulation questionnaires were used to obtain subjective supplementation of realism ratings and training effectiveness. Results Expert ratings demonstrated the model’s superiority to other procedural simulations in replicating procedural steps, bleeding, tissue texture and appearance. A significant difference between groups was demonstrated in CROMS [console time (P < 0.001), warm ischaemia time (P < 0.001), estimated blood loss (P < 0.001)] and GEARS (P < 0.001). Six major intra‐operative complications occurred only in novice simulations. GEARS scores highly correlated with the CROMS. Conclusions This perfused, procedural model offers an unprecedented realistic simulation platform, which incorporates objective, clinically relevant and procedure‐specific performance metrics.

Study Type – Prognosis (population‐based cohort study)
Level of Evidence 2b OBJECTIVES To estimate the risk of a second primary tumour (SPT) of the bladder in a cohort of childhood cancer survivors, investigate factors associated with a bladder SPT developing, and compare the risk observed with that expected from the general population. PATIENTS AND METHODS The analysis included 17 981 individuals diagnosed with childhood cancer, between 1940 and 1991 in Britain, and surviving for ≥5 years. Ascertainment of a bladder SPT was primarily through the National Health Service Central Registers (NHSCR). RESULTS From the NHSCR, 17 bladder SPTs were ascertained; this corresponded to four times (95% confidence interval 2.5–6.4) the expected number of bladder tumours. Standardized incidence ratios (SIRs) varied significantly (P < 0.05) by first primary tumour (FPT) type, follow‐up period, attained age and chemotherapy. The highest SIRs were in those: with heritable retinoblastoma (31.4); treated with chemotherapy (12.0); 0–9 years of follow‐up (10.8); and aged 0–19 years (9.3). The absolute excess risk (AER) for a bladder SPT was 3.7 cases/100 000 survivors per year. The AER varied significantly by FPT type, follow‐up period, attained age and gender. The highest AERs were in those: diagnosed with heritable retinoblastoma (34.0); 20–29 years of follow‐up (14.2); aged 40–49 years (13.0); and male (5.8). Using multivariable Cox regression, FPT and chemotherapy were significantly associated with the risk of a bladder SPT developing. By the age of 55 years, 0.4% of survivors developed a bladder SPT. CONCLUSION Although the absolute risk of a bladder tumour within childhood cancer survivors was low, the risk was four times that expected from the general population. Specific groups, e.g. survivors of heritable retinoblastoma and those treated with chemotherapy, were at the highest risk.