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Title: Genotoxic effects of orthopaedic wear debris on the bladder
Author: Maclean, Angus D.
ISNI:       0000 0004 5358 4767
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Concern over the biological effects of metal wear debris released from metal-on-metal bearing hips is high. Previous studies have suggested high 1evels of meta-I are found in patients' urine and there is an increase in bladder cancer after 10 years. This study investigates whether there is evidence of genotoxicity in patients' bladders after hip resurfacing. -Methods A cohort of 71 patients with metal-on-metal hip resurfacing two years post implant, were compared with a control group of 23 patients with no implant. Levels of cobalt, -chromium, molyb-clenum an-cl nickel were tested in blood and urine. A validated chromosomal test for the detection of bladder cancer (UroVysion) was used to detect chromosomal aneuploidy in patients' urine and buccal mucosa. Genetic mutation in bladder cancer genes p53 and FGFR3 were also screened for. Patients' urothelial cells were screened for appearances-suspicioI:Js -ofcancer. Atris-k -patient-s -wer-e -r-eferr-ed to the urology -se-rvic-es for cystoscopy. Nanoparticle tracking analysis was used to screen for nanoparticles in patients blood and urine. Results levels of cobalt and chromium were significantly raised in hip resurfacing patients' blood and urine, compared to controls. Levels of chromosomal aneuploidy were significantly raised in hip resurfaCing patients' urinary cells and -in their buccal mucosa. Fifteen h-ip resurfacing patients had -c~l/s neemed atypic-al or suspicious of bladder cancer when reviewed by a cytologist. Six of these patients had repeated atypical cytology, and one had a grade 1 transitional cell carcinoma diagnosed on cystoscopy. An additional population of nanoparticles was identified in post-operative urine. Discussion This study raises the concern of a metal induced carcinogenesis that may be occurring in the bladders of patients who have received meta1-on-metal hip resurfacing. The proposed mechanism is thattheur-othelium -is exposed to high levels -of -cobalt and chromium, which induce chromosomal aneuploidy in urothelial cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available