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result(s) for
"Jubber, Ibrahim"
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Occupational bladder cancer: A cross section survey of previous employments, tasks and exposures matched to cancer phenotypes
by
Goodwin, Louise
,
Catto, James W. F.
,
Griffin, Jon
in
Aged
,
Air Pollutants, Occupational - toxicity
,
Aircraft fuels
2020
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.
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.
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).
We identified multiple occupational tasks and contacts associated with bladder cancer. There were some associations with phenotype, although our study design precludes robust assessment.
Journal Article
Hyperthermic intravesical chemotherapy with mitomycin‐C for the treatment of high‐risk non‐muscle‐invasive bladder cancer patients
by
Rosario, Derek J.
,
Conroy, Samantha
,
Catto, James W. F.
in
acceptability
,
Bladder cancer
,
Cancer therapies
2023
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.
Journal Article
Gene of the month: GATA3
by
Cumberbatch, Marcus
,
Jubber, Ibrahim
,
Qiang, Zekai
in
Amino acids
,
Bladder cancer
,
Breast cancer
2023
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.
Journal Article
Bochdalek hernia causing type II respiratory failure in an elderly patient
2014
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.
Journal Article
Gene of the month: the uroplakins
2024
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.
Journal Article
Renal pseudoaneurysm: a rare and potentially fatal complication following ureteroscopy and laser fragmentation of stones
2018
Ureteroscopy and laser fragmentation of stones is a commonly used method to treat ureteric and renal calculi. We report the exceedingly rare finding of a renal pseudoaneurysm in an interpolar renal artery following ureteroscopy and laser stone fragmentation, which was successfully managed with angioembolisation.
Journal Article
Improving the management of people with a family history of breast cancer in primary care: before and after study of audit-based education
2013
Doc number: 105 Abstract 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.
Journal Article
Analysis of the Distal Urinary Tract in Larval and Adult Zebrafish Reveals Unrecognized Homology to the Human System
by
Morhardt, Duncan R
,
Renshaw, Stephen
,
Glover, Maggie
in
Danio rerio
,
Evolutionary Biology
,
Fertilization
2023
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 undertook multi-level analyses to determine the structure and composition of the distal urinary tract in the zebrafish. In silico searches identified uroplakin 1a, 2-like and 3-like genes in the zebrafish genome (orthologues to genes that encode proteins that characterise the urothelium in humans). In situ hybridization demonstrated uroplakin-1a expression 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.Competing Interest StatementThe authors have declared no competing interest.
Bochdalek hernia causing type II respiratory failure in an elderly patient
2014
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.
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