Gene of the month: the uroplakins.

Uroplakins are a family of membrane-spanning proteins highly specific to the urothelium. There are four uroplakin proteins in humans. These are encoded by the following UPK genes: UPK1A, UPK1B, UPK2 and UPK3 Uroplakin proteins span the apical membrane of umbrella cells of the urothelium, where they associate into urothelial plaques. This provides a barrier function to prevent passage of urine across the urothelium in the renal pelvis, ureters, and bladder. Uroplakins are also involved in developmental processes such as nephrogenesis. The specific localisation of uroplakins within the urothelium means that they are often expressed in primary and metastatic urothelial cell carcinoma and may be used as an immunohistochemical marker of urothelial malignancy.

Health-related quality of life after a diagnosis of bladder cancer: a longitudinal survey over the first year.

OBJECTIVES: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys. PATIENTS AND METHODS: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England. RESULTS: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population. DISCUSSION: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments.

Digital Tracking of Patients Undergoing Radical Cystectomy for Bladder Cancer: Daily Step Counts Before and After Surgery Within the iROC Randomised Controlled Trial.

BACKGROUND: Efforts to improve recovery after radical cystectomy (RC) are needed. OBJECTIVE: To investigate wrist-worn wearable activity trackers in RC participants. DESIGN, SETTING, AND PARTICIPANTS: An observational cohort study was conducted within the iROC randomised trial. INTERVENTION: Patients undergoing RC at nine cancer centres wore wrist-based trackers for 7 days (d) at intervals before and after surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Step counts were compared with participant and operative features, and recovery outcomes. RESULTS AND LIMITATIONS: Of 308 participants, 284 (92.2%) returned digital activity data at baseline (median 17 d [interquartile range: 8-32] before RC), and postoperatively (5 [5-6] d) and at weeks 5 (43 [38-43] d), 12 (94 [87-106] d), and 26 (192 [181-205] d) after RC. Compliance was affected by the time from surgery and a coronavirus disease 2019 pandemic lockdown (return rates fell to 0-7%, chi-square p < 0.001). Step counts dropped after surgery (mean of 28% of baseline), before recovering at 5 weeks (wk) (71% of baseline) and 12 wk (95% of baseline; all analysis of variance [ANOVA] p < 0.001). Baseline step counts were not associated with postoperative recovery or death. Patients with extended hospital stays had reduced postoperative step counts, with a difference of 2.2 d (95% confidence interval: 0.856-3.482 d) between the lowest third and highest two-third tertiles (linear regression analysis; p < 0.001). Additionally, they spent less time out of the hospital within 90 d of RC (80.3 vs 74.3 d, p = 0.013). Lower step counts at 5, 12, and 26 wk were seen in those seeking medical help and needing readmission (ANOVA p ≤ 0.002). CONCLUSIONS: Baseline step counts were not associated with recovery. Lower postoperative step counts were associated with longer length of stay at the hospital and postdischarge readmissions. Studies are required to determine whether low step counts can identify patients at a risk of developing complications. PATIENT SUMMARY: Postoperative step counts appear to be a promising tool to identify patients in the community needing medical help or readmission. More work is needed to understand which measures are most useful and how best to collect these.

Gene of the month: GATA3.

GATA binding protein 3 (GATA3) is a zinc-finger pioneer transcription factor involved in diverse processes. GATA3 regulates gene expression through binding nucleosomal DNA and facilitating chromatin remodelling. Post-translational modifications modulate its activity. During development, GATA3 plays a key role in cell differentiation. Mutations in GATA3 are linked to breast and bladder cancer. GATA3 expression is a feature of the luminal subtype of bladder cancer and has implications for immune status and therapeutic response. It also has clinical relevance in squamous cell carcinomas and soft tissue sarcomas. This paper reviews the structure and function of GATA3, its role in cancer and its use and pitfalls as an immunohistochemical marker.

Analysis of the distal urinary tract in larval and adult zebrafish reveals homology to the human system.

Little is known about the distal excretory component of the urinary tract in Danio rerio (zebrafish). This component is affected by many human diseases and disorders of development. Here, we have undertaken multi-level analyses to determine the structure and composition of the distal urinary tract in the zebrafish. In silico searches identified uroplakin 1a (ukp1a), uroplakin 2 (upk2) and uroplakin 3b (upk3b) genes in the zebrafish genome (orthologues to genes that encode urothelium-specific proteins in humans). In situ hybridization demonstrated ukp1a expression in the zebrafish pronephros and cloaca from 96 h post-fertilization. Haematoxylin and Eosin staining of adult zebrafish demonstrated two mesonephric ducts uniting into a urinary bladder that leads to a distinct urethral opening. Immunohistochemistry identified Uroplakin 1a, Uroplakin 2 and GATA3 expression in zebrafish urinary bladder cell layers that match human urothelial expression. Fluorescent dye injections demonstrated zebrafish urinary bladder function, including urine storage and 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.

Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors.

CONTEXT: Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention. OBJECTIVE: To perform an up-to-date systematic review of BC's epidemiology and external risk factors. EVIDENCE ACQUISITION: Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018. EVIDENCE SYNTHESIS: Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. CONCLUSIONS: We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention. PATIENT SUMMARY: Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer.

Lifestyle Factors in Patients with Bladder Cancer: A Contemporary Picture of Tobacco Smoking, Electronic Cigarette Use, Body Mass Index, and Levels of Physical Activity.

BACKGROUND: Little is known about contemporary lifestyle choices in patients with bladder cancer (BC). These choices include carcinogenic risk factors and could affect fitness to receive treatments. OBJECTIVE: To evaluate the contemporary lifestyle choices in BC patients. DESIGN, SETTING, AND PARTICIPANTS: Self-reported surveys from participants diagnosed with BC in the previous 10 yr captured smoking patterns, e-cigarette use, physical activity using the GODIN Leisure-Time Exercise Questionnaire, long-term conditions (LTCs), relationship status, sociodemographics, and body mass index (BMI; height and weight). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Findings were compared with the general population and men with prostate cancer. RESULTS AND LIMITATIONS: Completed surveys were received from 2092 participants. Most respondents were ex-smokers (61% vs 10% current vs 29% never). The use of e-cigarettes was uncommon (9%) and at lower rates than the age-equivalent general population. Passive smoke exposure was frequent (48%). Most participants (68%) were "insufficiently active" using the GODIN criteria and less physically active than the age-equivalent general population. Most respondents (44%) were classified as overweight (BMI 25-29.99) or obese (22%, BMI >30). Lifestyle factors varied with age, sex, socioeconomic deprivation, and LTCs. Younger participants were less likely to smoke (p < 0.001), more likely to have used e-cigarettes (p < 0.001), but more likely to have had passive smoke exposure (p = 0.008). Those from less affluent areas were more likely to smoke (p < 0.001), have used e-cigarettes (p < 0.001), and have had passive smoke exposure (p = 0.02). Females were less likely to be smokers (p < 0.001) but more likely to have been exposed to passive smoke (p < 0.001). CONCLUSIONS: Persons affected by BC often have smoking exposures and high BMI, and are insufficiently active. Rates of e-cigarette use were lower than in the general population. Efforts to improve quality of life in this cohort should include wider advocation of smoking cessation, perhaps including the use of e-cigarettes, and programmes to increase exercise and reduce BMI. PATIENT SUMMARY: We looked at the lifestyle choices, such as smoking, e-cigarette use, physical activity levels, and obesity, of patients following a bladder cancer diagnosis. We conclude that this population would benefit from healthy lifestyle interventions.

Hyperthermic intravesical chemotherapy with mitomycin-C for the treatment of high-risk non-muscle-invasive bladder cancer patients.

Objectives: The objectives of the study are to explore tolerability, acceptability and oncological outcomes for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with hyperthermic intravesical chemotherapy (HIVEC) and mitomycin-C (MMC) at our institution. Patients and Methods: Our single-institution, observational study consists of consecutive high-risk NMIBC patients treated with HIVEC and MMC. Our HIVEC protocol included six weekly instillations (induction), followed by two further cycles of three instillations (maintenance) (6 + 3 + 3) if there was cystoscopic response. Patient demographics, instillation dates and adverse events (AEs) were collected prospectively in our dedicated HIVEC clinic. Retrospective case-note review was performed to evaluate oncological outcomes. Primary outcomes were tolerability and acceptability of HIVEC protocol; secondary outcomes were 12-month recurrence-free, progression-free and overall survival. Results: In total, 57 patients (median age 80.3 years) received HIVEC and MMC, with a median follow-up of 18 months. Of these, 40 (70.2%) had recurrent tumours, and 29 (50.9%) had received prior Bacillus Calmette-Guérin (BCG). HIVEC induction was completed by 47 (82.5%) patients, but only 19 (33.3%) completed the full protocol. Disease recurrence (28.9%) and AEs (28.9%) were the most common reasons for incompletion of protocol; five (13.2%) patients stopped treatment due to logistical challenges. AEs occurred in 20 (35.1%) patients; the most frequently documented were rash (10.5%), urinary tract infection (8.8%) and bladder spasm (8.8%). Progression during treatment occurred in 11 (19.3%) patients, 4 (7.0%) of whom had muscle invasion and 5 (8.8%) subsequently required radical treatment. Patients who had received prior BCG were significantly more likely to progress (p = 0.04). 12-month recurrence-free, progression-free and overall survival rates were 67.5%, 82.2%, and 94.7%, respectively. Conclusions: Our single-institution experience suggests that HIVEC and MMC are tolerable and acceptable. Oncological outcomes in this predominantly elderly, pretreated cohort are promising; however, disease progression was higher in patients pretreated with BCG. Further randomised noninferiority trials comparing HIVEC versus BCG in high-risk NMIBC are required.

Sexual Activity, Function and Dysfunction After a Diagnosis of Bladder Cancer.

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<0.001) and had worse mean scores for intimacy problems (29.1 [radical treatment] vs 12.1, P<0.001), male sexual problems (72.2 [radical treatment] vs 45.7, P<0.001) and overall sexual function (17.1 [radical treatment] vs 20.3, P=0.01). 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. Jubber I, Rogers Z, Catto JWF, et al. Sexual Activity, Function and Dysfunction After a Diagnosis of Bladder Cancer. J Sex Med 2022;19:1431-1441.

Impact of Anaesthetist Volume on Radical Cystectomy Outcomes.

BACKGROUND: 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. OBJECTIVE: We sought to examine RC outcomes stratified by anaesthetist volume using a contemporary homogenous series. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of a prospectively collected, single-surgeon database of RC patients over a 10-yr period. INTERVENTION: Four hundred and fifty-three consecutive patients underwent RC, including 430 (95%) with anaesthetist annotation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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, p<0.001), 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). CONCLUSIONS: 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. PATIENT SUMMARY: 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.

The Impact of Centralised Services on Metric Reflecting High-quality Performance: Outcomes from 1110 Consecutive Radical Cystectomies at a Single Centre.

BACKGROUND: The 2002 National Institute for Health and Care Excellence guidance on centralisation of radical cystectomy (RC) coincided with changes in practice: use of neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND), and RC for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). OBJECTIVE: To report the outcomes of RC at a single centre and to compare trends in survival with respect to centralisation and change in RC practice. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively between 1 January 1994 and 31 December 2016. Patients with urothelial cell carcinoma (UCC) were selected. Outcomes from 1994 to 2007 (before centralisation, era 1) were compared with those from 2008 to 2016 (after centralisation, era 2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was disease-specific mortality. Secondary outcomes were survival and use of NAC and PLND. RESULTS AND LIMITATIONS: Overall, 1100 RCs (era 1, 316; era 2, 794) were performed for UCC. Median (interquartile range [IQR]) follow-up was 28.5 (11.9-57.4) mo. RC for NMIBC was 36.2% versus 51.3% (p<0.001), NAC use was 2.2% versus 31.6% (p<0.001), and PLND use was 59.7% versus 76.4% (p<0.001) in era 1 versus era 2. The 30-d (1.6% [era 1] vs 0.8% [era 2], p=0.21) and 90-d (4.1% vs 2.6%, p=0.2) mortality rates did not differ with respect to RC year. Five-year disease-specific survival (DSS) was 56.0% in era 1 versus 79.0% in era 2 (p<0.001). RC for patients aged ≥75 yr was 13.9% versus 28.1% (p<0.001) and 30-d mortality in this group was 4.5% versus 0% (p=0.001) in era 1 versus era 2. The study is limited by its retrospective design. CONCLUSIONS: Centralisation was associated with higher rates of NAC and PLND use, and increased RC performed for older patients and patients with HR-NMIBC. DSS was higher and RC appeared to be safer for older patients (fewer postoperative mortalities) after centralisation. PATIENT SUMMARY: We looked at outcomes from bladder removal for bladder cancer. Survival outcomes improved following centralisation of services. Surgery appeared to be safer for older patients, as there were fewer postoperative mortalities after centralisation. Centralisation of radical cystectomy (RC) services was associated with higher rates of neoadjuvant chemotherapy and pelvic lymph node dissection use, and increased usage of RC for older patients with high-risk non-muscle-invasive bladder cancer. Survival outcomes from RC were superior after centralisation and safer for older patients undergoing RC (fewer postoperative mortalities).

Occupational bladder cancer: A cross section survey of previous employments, tasks and exposures matched to cancer phenotypes.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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<0.001), but more likely than men to inhale environmental tobacco smoke at home (82% vs. 74% p = 0.08) and use hair dye (56% vs. 3%, p<0.001). Contact with potential carcinogens occurred in 282 (62%) participants (mean 3.1 per worker (range 0-14)). High-grade cancer was more common than low-grade disease in workers from the steel, foundry, metal, engineering and transport industries (p<0.05), and in workers exposed to crack detection dyes, chromium, coal/oil/gas by-products, diesel fumes/fuel/aircraft fuel and solvents (such as trichloroethylene). Higher staged cancers were frequent in workers exposed to Chromium, coal products and diesel exhaust fumes/fuel (p<0.05). Various workers (e.g. exposed to diesel fuels or fumes (Cox, HR 1.97 (95% CI 1.31-2.98) p = 0.001), employed in a garage (HR 2.19 (95% CI 1.31-3.63) p = 0.001), undertaking plumbing/gas fitting/ventilation (HR 2.15 (95% CI 1.15-4.01) p = 0.017), undertaking welding (HR 1.85 (95% CI 1.24-2.77) p = 0.003) and exposed to welding materials (HR 1.92 (95% CI 1.27-2.91) p = 0.002)) were more likely to have disease progression and receive radical treatment than others. Fewer than expected deaths were seen in healthcare workers (HR 0.17 (95% CI 0.04-0.70) p = 0.014). CONCLUSIONS: We identified multiple occupational tasks and contacts associated with bladder cancer. There were some associations with phenotype, although our study design precludes robust assessment.

Reporting Radical Cystectomy Outcomes Following Implementation of Enhanced Recovery After Surgery Protocols: A Systematic Review and Individual Patient Data Meta-analysis.

CONTEXT: Enhanced Recovery After Surgery (ERAS) is a perioperative approach to managing surgical patients. The impact of ERAS on radical cystectomy (RC) outcomes remains understudied. OBJECTIVE: To review the literature regarding ERAS protocols and RC outcomes. The primary outcome was hospital length of stay (LOS). EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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). CONCLUSIONS: 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. PATIENT SUMMARY: 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.

Non-visible haematuria for the Detection of Bladder, Upper Tract, and Kidney Cancer: An Updated Systematic Review and Meta-analysis.

CONTEXT: 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. OBJECTIVE: 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). EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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 aged <40yr), 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.

Prostatic capsular incision during radical prostatectomy has important oncological implications: a systematic review and meta-analysis.

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.

Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018.

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.

Repeat Transurethral Resection in Non-muscle-invasive Bladder Cancer: A Systematic Review.

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 hernia causing type II respiratory failure in an elderly patient.

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.