Evolution of the neobladder: A critical review of open and intracorporeal neobladder reconstruction techniques

Orthotopic neobladder is an attractive alternative to the ileal conduit following radical cystectomy. Robotic cystectomy is gaining popularity although the uptake of neobladder reconstruction is low, with the majority of cases being constructed extracorporeally via a mini-laparotomy. Minimally invasive cystectomy using the robotic platform facilitates intracorporeal neobladder reconstruction and several techniques have been described. This review discusses issues relating to patient selection, and describes existing techniques of open surgical neobladder reconstruction and their evolution to suit an intracorporeal approach. A Medline search for publications from January 1970 to September 2015 with the following keyword search criteria was performed: radical cystectomy, robotic cystectomy, intracorporeal, neobladder, orthotopic bladder reconstruction, surgical technique, patient selection and ureteric–ileal anastomosis

Bone marrow and chelatable iron in patients with protein energy malnutrition

Objectives: To examine the iron status of malnourished children by comparing bone marrow iron deposits in children with protein energy malnutrition with those in well-nourished controls, and measuring chelatable urinary iron excretion in children with kwashiorkor. Design: Bone marrow iron was assessed histologicaHy in postmortem specimens from children with kwashiorkor or marasmus, and from controls. Twenty-four-hour urinary iron was measured in children with severe kwashiorkor, half of whom received 10 mg/kg of intramuscular desferrioxamine (DFO) on admission.  Setting: Red Cross War Memorial Children's Hospital, Cape Town. Subjects: Thirteen children with kwashiorkor, 6 with marasmus and 16 well-nourished children underwent bone marrow examination. Urinary iron excretion was assayed in 17 children with kwashiorkor. Results: Stainable iron was present in the bone marrow of half the children with kwashiorkor but in only 1 child in each of the other groups. The median iron excretion was 945.5 µg/24 hours in the DFO group compared with 28.5 µg/24 hours in the non-DFO group. Conclusions: There is an apparent excess of iron which may predispose to bacterial infections and free radicalmediated injury in children with kwashiorkor. S AFr Med J 1996; 86: 1410-141

The role of circulating tumour cells and nucleic acids in blood for the detection of bladder cancer: A systematic review

BACKGROUND: Blood-based biomarkers are a neglected resource in bladder cancer, where the mainstay of focus has been on urinary biomarkers. However, blood-based biomarkers are gaining popularity in other solid cancers, particularly circulating tumour cells (CTCs) and circulating nucleic acids. In this systematic review, we identify and discuss the diagnostic value of CTC, cell-free DNA and RNA based biomarkers in bladder cancer. METHODS: A MEDLINE/Pubmed systematic search was performed using the following keywords: (bladder cancer) AND (blood OR plasma OR serum) AND biomarker AND (DNA OR RNA OR cfDNA OR cell-free DNA OR RNA OR CTC). All studies including blood-based biomarkers based on DNA, RNA and CTCs were reviewed. Of the included studies, studies reporting sensitivity, specificity and/or AUC/ROC values were further described. RESULTS: Systematic searched yielded 47 studies that were eligible, of which 21, 19 and 3 studies reported DNA, RNA and CTC biomarkers respectively. 15 of these studies included sensitivity, specificity and/or AUC/ROC values. Biomarkers sensitivity and specificity ranged widely at 2.4-97.6% and 43.3-100% respectively. Median number of patients recruited in the studies was 56 (IQR 41-90). Only 3 studies included an independent validation cohort. The highest sensitivity and specificity pairing achieved in the validation cohort was 80.0% and 89.1% respectively. CONCLUSIONS: This systematic review provides a comprehensive overview of the blood-based CTC and nucleic acid biomarkers that have been investigated. An overlap in interest of targets between studies suggests that these could be promising biomarkers, but few biomarkers achieve high sensitivity and specificity, and fewer still have been validated independently

Ozone’s Impact on Public Health: Contributions from Indoor Exposures to Ozone and Products of Ozone-Initiated Chemistry

OBJECTIVE: The associations between ozone concentrations measured outdoors and both morbidity and mortality may be partially due to indoor exposures to ozone and ozone-initiated oxidation products. In this article I examine the contributions of such indoor exposures to overall ozone-related health effects by extensive review of the literature as well as further analyses of published data. FINDINGS: Daily inhalation intakes of indoor ozone (micrograms per day) are estimated to be between 25 and 60% of total daily ozone intake. This is especially noteworthy in light of recent work indicating little, if any, threshold for ozone’s impact on mortality. Additionally, the present study estimates that average daily indoor intakes of ozone oxidation products are roughly one-third to twice the indoor inhalation intake of ozone alone. Some of these oxidation products are known or suspected to adversely affect human health (e.g., formaldehyde, acrolein, hydroperoxides, fine and ultrafine particles). Indirect evidence supports connections between morbidity/mortality and exposures to indoor ozone and its oxidation products. For example, cities with stronger associations between outdoor ozone and mortality tend to have residences that are older and less likely to have central air conditioning, which implies greater transport of ozone from outdoors to indoors. CONCLUSIONS: Indoor exposures to ozone and its oxidation products can be reduced by filtering ozone from ventilation air and limiting the indoor use of products and materials whose emissions react with ozone. Such steps might be especially valuable in schools, hospitals, and childcare centers in regions that routinely experience elevated outdoor ozone concentrations

Novel urinary biomarkers for the detection of bladder cancer: A systematic review

BACKGROUND: Urinary biomarkers for the diagnosis of bladder cancer represents an area of considerable research which has been tested in both patients presenting with haematuria and non-muscle invasive bladder cancer patients requiring surveillance cystoscopy. In this systematic review, we identify and appraise the diagnostic sensitive and specificity of reported novel biomarkers of different 'omic' class and highlight promising biomarkers investigated to date. METHODS: A MEDLINE/Pubmed systematic search was performed between January 2013 and July 2017 using the following keywords: (bladder cancer OR transitional cell carcinoma OR urothelial cell carcinoma) AND (detection OR diagnosis) AND urine AND (biomarker OR assay). All studies had a minimum of 20 patients in both bladder cancer and control arms and reported sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. QUADAS-2 tool was used to assess risk of bias and applicability of studies. The search protocol was registered in the PROSPERO database (CRD42016049918). RESULTS: Systematic search yielded 115 reports were included for analysis. In single target biomarkers had a sensitivity of 2-94%, specificity of 46-100%, positive predictive value (PPV) of 47-100% and negative predictive value (NPV) of 21-94%. Multi-target biomarkers achieved a sensitivity of 24-100%, specificity of 48-100%, PPV of 42-95% and NPV of 32-100%. 50 studies achieved a sensitivity and specificity of ≥80%. Protein (n = 59) and transcriptomic (n = 21) biomarkers represents the most studied biomarkers. Multi-target biomarker panels had a better diagnostic accuracy compared to single biomarker targets. Urinary cytology with urinary biomarkers improved the diagnostic ability of the biomarker. The sensitivity and specificity of biomarkers were higher for primary diagnosis compared to patients in the surveillance setting. Most studies were case control studies and did not have a predefined threshold to determine a positive test result indicating a possible risk of bias. CONCLUSION: This comprehensive systematic review provides an update on urinary biomarkers of different 'omic' class and highlights promising biomarkers. Few biomarkers achieve a high sensitivity and negative predictive value. Such biomarkers will require external validation in a prospective observational setting before adoption in clinical practice

Delayed blood transfusion is associated with mortality following radical cystectomy

Objectives: To examine the temporal association between blood transfusion and 90-day mortality in patients with bladder cancer treated with radical cystectomy. / Methods: This represents a retrospective cohort study of patients treated with radical cystectomy within the Premier Hospital network between 2003 and 2015. Patients outcomes were stratified those who received early blood transfusion (day of surgery) vs delayed blood transfusion (postoperative day ≥1) during the index admission. Primary end point was 90-day mortality following surgery. / Results: The median age of 12,056 patients identified was 70 years. A total of 7,201 (59.7%) patients received blood transfusion. Within 90 days following surgery, 57 (2.2%), 162 (5.9%) and 123 (6.7%) patients in the early, delayed and both early and delayed transfused patients died respectively. Following multivariate logistic regression to account for patient (age and Charlson Comorbidity Index [CCI]) and hospital (surgeon volume, surgical approach and academic status) factors, delayed blood transfusion was independently associated with 90-day mortality (Odds ratio [OR], 2.64; 95% Confidence Interval [CI], 1.98–3.53; p < 0.001). A sensitivity analysis defining early blood transfusion as <2 days postoperatively, increased 90-day mortality persisted in patients receiving delayed transfusion (OR, 2.20; 95% CI, 1.63-3.00; p < 0.001). Older patients (≥77 years) with the highest CCI (≥2) had a 7% absolute increase in the predicted probability of 90-day mortality if they were transfused late compared to patients transfused early. / Conclusion: Patient undergoing cystectomy may benefit from expedited transfusion to prevent subsequent clinical deterioration which may lead to patient mortality. Future work is needed to elucidate the optimal timing of blood transfusion

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: A prospective cohort study

BACKGROUND: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). METHODS: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. RESULTS: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. CONCLUSIONS: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series

Mix methods approach to explore patients' perspectives on the acceptability of a urinary biomarker test in replacement of cystoscopy in bladder cancer surveillance

OBJECTIVE: To determine the minimal accepted sensitivity (MAS) of a urine biomarker that patients are willing to accept to replace cystoscopy and to qualitatively assess their views and reasons. PATIENT AND METHODS: Patients were part of a prospective multi-center observational study recruiting patients with bladder cancer for a urine biomarker study (DETECT II; ClinicalTrials.gov: NCT02781428). A mix methods approach comprising of 1) Questionnaire to assess patients' experience with cystoscopy and patients' preference for cystoscopy vs urinary biomarker and 2). Semi-structured interviews to understand patient views, choice and reasons for their preference. RESULTS: A urine biomarker with MAS of 90% would be accepted by 75.8% of patients. This is despite a high self-reported prevalence of hematuria (51.0%), dysuria/ lower urinary tract symptoms (69.1%) and urinary tract infection requiring antibiotics (25.8%). There was no association between MAS with patient demographics, adverse events experienced, cancer characteristics and distance of patients' home to hospital. Qualitative analysis suggest that patients acknowledge that cystoscopy is invasive, embarrassing and associated with adverse events but are willing to tolerate the procedure due to a high sensitivity. Patients have confidence in cystoscopy and appreciate the visual diagnosis of cancer. Both low and high-risk patients would consider a biomarker with a reported sensitivity similar to cystoscopy. CONCLUSION: Patients value the high sensitivity cystoscopy accords despite the reported discomfort and adverse events experienced following cystoscopy. The sensitivity of a urinary biomarker must be close to cystoscopy before patients' acceptance