title: A novel precision-engineered microfiltration device for capture and characterisation of bladder cancer cells in urine.
abstract: BACKGROUND
  Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells.
  
  
  OBJECTIVE
  Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection.
  
  
  METHODS
  A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies.
  
  
  RESULTS
  Five samples were paucicellular by standard cytology; no samples processed by microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p<0.001). Microfilter cytology was more concordant (κ=50.4%) than standard cytology (κ=33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by microfilter cytology compared to 5.5 min by standard cytology. Median microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively.
  
  
  CONCLUSIONS
  The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.
authors.affiliation: Urologie am Ring, Kaiser Wilhelm Ring 36, Cologne, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Birkhahn
authors.forename: Anirban P
authors.initials: AP
authors.lastname: Mitra
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Williams
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Barr
authors.forename: Eila C
authors.initials: EC
authors.lastname: Skinner
authors.forename: John P
authors.initials: JP
authors.lastname: Stein
authors.forename: Donald G
authors.initials: DG
authors.lastname: Skinner
authors.forename: Yu-Chong
authors.initials: YC
authors.lastname: Tai
authors.forename: Ram H
authors.initials: RH
authors.lastname: Datar
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cote
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000652:urine*; D003581:Cytodiagnosis; D055088:Early Detection of Cancer; D005260:Female; D005374:Filtration / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D036103:Nanotechnology; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor
keywords: Bladder cancer; Nanotechnology; Screening; Surveillance; Urine cytology