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Little is known about the distal excretory component of the urinary tract inDanio rerio(zebrafish). This component is affected by many human diseases and disorders of development. Here, we undertook multi-level analyses to determine the structure and composition of the distal urinary tract in the zebrafish.In silicosearches identifieduroplakin 1a, 2-likeand3-likegenes in the zebrafish genome (orthologues to genes that encode proteins that characterise the urothelium in humans).In situhybridization demonstrateduroplakin-1aexpression in the zebrafish pronephros and cloaca from 96 hours post-fertilisation. H&E sectioning of adult zebrafish demonstrated two mesonephric ducts uniting into a urinary bladder which leads to a distinct urethral opening. Immunohistochemistry identified Uroplakin 1a and 2 expression within the urothelial luminal surface and Gata3 expression in cell layers that match human urothelial expression. Fluorescent dye injections demonstrated urinary bladder function, including urine storage, intermittent micturition, and a urethral orifice separate from the larger anal canal and rectum. Our findings reveal homology between the urinary tracts of zebrafish and humans and offer the former as a model system to study disease.Summary StatementThe excretory components of the distal urinary tract in larval and adult zebrafish have been incompletely evaluated. Here, we demonstrate close homology in urinary tract anatomy between zebrafish and human, including the presence of a distinct adult urinary bladder capable of periodic micturition

Background Sexual dysfunction is common in those affected by cancer and local and radical treatments for Bladder Cancer (BC) can affect sexual function directly. Aim To evaluate sexual function following a bladder cancer (BC) diagnosis. Methods Self-reported sexual function was collected 10 years after a diagnosis of BC as part of a cross-sectional patient reported outcome measure (PROM) survey exploring life after BC diagnosis and treatment. Outcomes Participants completed a combined EORTC QLQ-BLM30 and QLQ-NMIBC24 questionnaire, including questions on sexual activity, intimacy, erectile/ejaculatory function and vaginal dryness. Results A total of 1796 participants returned a completed survey out of 3279 eligible participants (55%). Of the participants who returned a completed survey, a total of 1530 (85%) participants answered sexual function questions. The median (IQR) age was 75 (70–81). Participants were predominantly men (78%) and married/in civil partnerships (66%). In total, 31% were sexually active. Vaginal dryness was common (66%) in women. Erectile and ejaculatory dysfunction (80% and 58% respectively) were common in men. Compared to TURBT +/- intravesical treatments, those who had radical treatment were less likely to be sexually active (adjusted OR 0.56, 95% CI: 0.44–0.72, P Clinical Implications These findings highlight the magnitude of sexual dysfunction in the BC patient cohort and can help inform patients during the pre-op counselling process and shared decision making prior to BC treatments. Strengths and Limitations This study provides the largest in-depth analysis of sexual activity and function after BC diagnosis and treatment, to date. Limitations include the lack of data on participants’ sexual function prior to BC treatment and the heterogeneity with respect to time passed since last BC treatment. Conclusion Sexual dysfunction in BC patients is common and rates appear higher following radical treatments compared to endoscopic. It is important to elicit these problems in clinics to enable counselling and treatment.

Enhanced Recovery After Surgery (ERAS) is a perioperative approach to managing surgical patients. The impact of ERAS on radical cystectomy (RC) outcomes remains understudied.To review the literature regarding ERAS protocols and RC outcomes. The primary outcome was hospital length of stay (LOS).A systematic review of the articles published from 1970 through 2018 was conducted. Individual patient data (IPD) were requested and a meta-analysis was performed.A total of 4197 articles were retrieved and 22 (reporting 4048 patients) were selected for the review. LOS followed by 30-d and that followed by 90-d complications were the most common endpoints. ERAS use was associated with reduced morbidity, quicker bowel recovery, and shorter LOS, without affecting mortality. IPD were obtained for 2077 patients from 11 studies. In multivariable models, LOS was associated with ERAS use (regression coefficient: -4.54 [95% confidence interval {CI}: -5.79 to -3.28] d with ERAS p 0.001) and Charlson Comorbidity Index (+1.64 [1.38-1.90] d for each point increase, p 0.001), and varied between hospitals (from -1.59 [-3.03 to -0.14] to +4.55 [1.89-7.21] d, p 0.03). Individual ERAS components associated with shorter LOS included no nasogastric (NG) tube (-8.70 [-11.9 to -5.53] d, p 0.001) and local anesthesia blocks compared with regional anesthesia (-3.29 [-6.31 to -0.27] d, p = 0.03).ERAS protocols were associated with reduced LOS and postoperative complication rate. Avoidance of NG tubes and use of local anesthesia blocks were significantly associated with reduced LOS. These findings reflect different components of recovery, which ERAS can optimize and further support documentation of the use of ERAS components when reporting RC outcomes.Use of enhanced recovery in patients undergoing surgery to remove the bladder is associated with fewer surgical complications and a shorter hospital stay. Avoidance of nasogastric tubes and use of local anesthesia after the operation were associated with a shorter length of stay.

CONTEXT: Bladder cancer (BC) is a significant health problem, and understanding the risk factors for this disease could improve prevention and early detection.OBJECTIVE: To provide a systematic review and summary of novel developments in epidemiology and risk factors for BC.EVIDENCE ACQUISITION: A systematic review of original articles was performed by two pairs of reviewers (M.G.C., I.J., F.E., and K.P.) using PubMed/Medline in December 2017, updated in April 2018. To address our primary objective of reporting contemporary studies, we restricted our search to include studies from the last 5yr. We subdivided our review according to specific risk factors (PICO [Population Intervention Comparator Outcome]).EVIDENCE SYNTHESIS: Our search found 2191 articles, of which 279 full-text manuscripts were included. We separated our manuscripts by the specific risk factor they addressed (PICO). According to GLOBOCAN estimates, there were 430000 new BC cases and 165000 deaths worldwide in 2012. Tobacco smoking and occupational exposure to carcinogens remain the factors with the highest attributable risk. The literature was limited by heterogeneity of data.CONCLUSIONS: Evidence is emerging regarding gene-environment interactions, particularly for tobacco and occupational exposures. In some populations, incidence rates are declining, which may reflect a decrease in smoking. Standardisation of reporting may help improve epidemiologic evaluation of risk.PATIENT SUMMARY: Bladder cancer is common worldwide, and the main risk factors are tobacco smoking and exposure to certain chemicals in the working and general environments. There is ongoing research to identify and reduce risk factors, as well as to understand the impact of genetics on bladder cancer risk.

Introduction Prostatic capsular incision (CapI) is an iatrogenic breach of the prostatic capsule during radical prostatectomy (RP) that can cause positive surgical margins (PSMs) in organ‐confined (pT2) prostate cancer, or the retention of benign prostatic tissue. We systematically interrogated the literature in order to clarify the definition of CapI, and the implications of this event for rates of PSM and biochemical recurrence (BCR). Methods A literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) criteria using the search terms ‘capsular incision’ AND ‘prostatectomy’, and variations of each. In all, 18 studies were eligible for inclusion. Results A total of 51 057 RP specimens were included. The incidence of CapI ranged from 1.3% to 54.3%. CapI definitions varied and included a breach of the prostatic capsule ‘exposing both benign or malignant prostate cancer cells’, ‘malignant tissue only’, or ‘benign tissue only’. The incidence of PSMs due to CapI ranged from 2.8% to 71.7%. Our meta‐analysis results found that when CapI was defined as ‘exposing malignant tissue only in organ‐confined prostate cancer’ there was an increased risk of BCR compared to patients with pT2 disease and no CapI (relative risk 3.53, 95% confidence interval 2.82–4.41; P < 0.001). Conclusions The absolute impact of CapI on oncological outcomes is currently unclear due to inconsistent definitions. However, the data imply an association between CapI and PSMs and BCR. Reporting of possible areas of CapI on the operation note, or marking areas of concern on the specimen, are critical to assist CapI recognition by the pathologist.

Objectives\ud Up to 10% of Bladder Cancers may arise following occupational exposure to carcinogens. We hypothesised that different cancer phenotypes reflected different patterns of occupational exposure.\ud \ud Methods\ud Consecutive participants, with bladder cancer, self-completed a structured questionnaire detailing employment, tasks, exposures, smoking, lifestyle and family history. Our primary outcome was association between cancer phenotype and occupational details.\ud \ud Results\ud We collected questionnaires from 536 patients, of whom 454 (85%) participants (352 men and 102 women) were included. Women were less likely to be smokers (68% vs. 81% Chi sq. p

Non-visible haematuria (NVH) is a common finding and may indicate undiagnosed urological cancer. The optimal investigation of NVH is unclear, given the incidence of cancer and the public health implications of testing all individuals with this finding.We review contemporary literature to determine the association of NVH with the diagnosis of bladder cancer (BC), upper tract urothelial carcinoma (UTUC), and kidney cancer (KC).A systematic review of original articles in English was completed in May 2019. Meta-analyses for the diagnostic accuracy of NVH and urine cytology were performed.We screened 1529 articles and selected 78 manuscripts that fulfilled our inclusion criteria for narrative synthesis. Forty manuscripts were eligible for a meta-analysis (reporting 19 193 persons). The likelihood of a urological cancer in patients with NVH increased with age (1% in those aged40yr), male sex, and cigarette smoking. Less than 1% of patients are found to have a urological cancer after a negative NVH evaluation. Cancer detection rates in individuals evaluated for NVH ranged from 0% to 16% for BC in 37 studies, 0% to 3.5% for UTUC in 30 studies, and 0% to 9.7% for KC in 29 studies. Substantial statistical heterogeneity was present for the meta-analysis of detection rates.We present an up-to-date review of the association of NVH with the diagnosis of BC, UTUC, and KC. Individuals with dipstick positive haematuria aged ≥40yr, who have had potential precipitating causes excluded, should undergo an evaluation. Re-evaluation of patients with unremarkable initial investigations should be performed in high-risk patients or if new symptoms occur.One in five people have microscopic traces of blood in their urine. This is an important indicator of urological cancer. Investigating all patients is uncomfortable and expensive. We evaluate the risk of cancer and estimate risks to groups of individuals.

Radical cystectomy (RC) is a gold standard treatment for aggressive bladder cancer. Higher surgical volumes through centralisation are associated with improved RC outcomes. The impact of anaesthetist experience and RC volume on outcomes is less clear.We sought to examine RC outcomes stratified by anaesthetist volume using a contemporary homogenous series.A retrospective analysis of a prospectively collected, single-surgeon database of RC patients over a 10-yr period.Four hundred and fifty-three consecutive patients underwent RC, including 430 (95%) with anaesthetist annotation.Anaesthetists were stratified into low- (10 cases) and high-volume (≥10 cases) classes. Primary outcomes were blood loss, transfusion rates, length of stay (LOS), and postoperative mortality.In total, 63 anaesthetists were included for analysis (median two RCs per anaesthetist). Of 63 anaesthetists, 56 (88.9%) and seven (11.1%) were classified, respectively, into low and high volume, and these provided cover for 110 (25.6%) and 320 (74.4%) patients, respectively. When comparing high- versus low-volume anaesthetists, there were shorter LOS (median [interquartile range {IQR}]: 10 [6-14] vs 12 [7-19] d, p = 0.008), lower blood loss (median [IQR]: 600 [384-1000] vs 800 [500-1275] ml, p0.001), and lower transfusion rate (23/320, 7.2% vs 22/110, 20%; p 0.001). There was no difference in disease-specific mortality, overall mortality, or readmission rates. In multivariable analysis, a high anaesthetist volume was independently associated with transfusion rate (odds ratio 0.24 [0.07-0.83], p = 0.02).Higher-volume anaesthetists have lower transfusion rates for RC patients. Whilst LOS and blood loss may also differ with experience, there is no difference in mortality after RC.Radical cystectomy is a major operation. Experienced anaesthetists give fewer blood products to patients undergoing this operation. They may also help reduce blood loss and speed recovery. However, all other recovery measures were similar.

Context Initial treatment for most bladder cancers (BCs) involves transurethral resection (TUR) or tumours. Often more cancer is found after the initial treatment in around half of patients, requiring a second resection. Repeat transurethral resection (reTUR) is recommended for high-risk, non–muscle-invasive bladder cancer (NMIBC) to remove any residual disease and improve cancer outcomes. Objective To systematically review the practice and therapeutic benefit of an early reTUR for high-risk NMIBC. Evidence acquisition A systematic review of original articles was performed using PubMed/Medline and Web of Science databases in December 2016 (initial) and October 2017 (final). We searched the references of included papers. Evidence synthesis We screened 15 209 manuscripts and selected 31 detailing 8409 persons with high-grade Ta and T1BC for inclusion. Detrusor muscle was found at initial TUR histology in 30–100% of cases. Residual tumour at reTUR was found in 17–67% of patients following Ta and in 20–71% following T1 cancer. Most residual tumours (36–86%) were found at the original resection site. Upstaging occurred in 0–8% (Ta to ≥T1) and 0–32% (T1 to ≥T2) of cases. Conflicting data report the impact of reTUR on subsequent recurrence and cancer-specific mortality. Recurrence for Ta was 16% in the reTUR group versus 58% in the non-reTUR group. For T1, recurrence ranged from 18% to 56%, but no clear trend was identified between reTUR and control. No clear relationship between reTUR and progression was found for Ta, although for T1 rates were higher in the non-reTUR group in series with control populations (5/6 studies). Overall mortality was slightly reduced in the reTUR group in two studies with controls (22–30% vs 26–36% [no reTUR]). Conclusions Residual tumour is common after TUR for high-risk NMIBC. The reTUR helps in the diagnosis of this residual cancer and may improve outcomes for cancers initially staged as T1. Patient summary Some bladder cancers (BCs) are aggressive but confined to the bladder surface. Initial treatment includes endoscopic resection. More cancer is found after the initial treatment in approximately half of patients. In the aggressive but confined group of BC, a second resection, a few weeks after the first, may help find this residual cancer and improve outcomes, although the evidence quality for this is weak.

Bochdalek hernias occur as a result of a congenital defect in the diaphragm enabling abdominal viscera to enter the thoracic cavity restricting lung expansion and ventilation. Bochdalek hernias, in the majority of cases, present in neonates and very rarely in adults. To the best of our knowledge, there are only four published cases of Bochdalek hernia in the adult population causing respiratory failure. We present the case of an 87-year-old woman who had three admissions in the past 6 months with type II respiratory failure due to a Bochdalek hernia which we believe was congenital but had gradually increased in size over the years to cause progressive decompensation with acute exacerbations requiring non-invasive ventilation.

Background In England, guidance from National Institute for Clinical Excellence (NICE) states women with a family history of breast cancer presenting to primary care should be reassured or referred. We reviewed the evidence for interventions that might be applied in primary care and conducted an audit of whether low risk women are correctly advised and flagged. Methods We conducted a literature review to identify modifiable risk factors. We extracted routinely collected data from the computerised medical record systems of 6 general practices (population approximately 30,000); of the variables identified in the guidance. We implemented a quality improvement (QI) intervention called audit-based education (ABE) comparing participant practices with guidelines and each other before and after; we report odds ratios (OR) of any change in data recording. Results The review revealed evidence for advising on: diet, weight control, physical exercise, and alcohol. The proportion of patients with recordings of family history of: disease, neoplasms, and breast cancer were: 39.3%, 5.1% and 1.3% respectively. There was no significant change in the recording of family history of disease or cancer; OR 1.02 (95% CI 0.98-1.06); and 1.08 (95% CI 0.99-1.17) respectively. Recording of alcohol consumption and smoking both increased significantly; OR 1.36 (95% CI 1.30-1.43); and 1.42 (95% CI 1.27-1.60) respectively. Recording lifestyle advice fell; OR 0.84 (95% CI 0.81-0.88). Conclusions The study informs about current data recording and willingness to engage in ABE. Recording of risk factors improved after the intervention. Further QI is needed to achieve adherence to current guidance.