title: The role of haematuria in bladder cancer screening among men with former occupational exposure to aromatic amines.
abstract: Study Type - Diagnostic (validating cohort).
  
  
  METHODS
  1b. What's known on the subject? and What does the study add? Microscopic haematuria (µH) is frequently detected in elderly adults. The American Urological Association recommends the follow-up of subjects with µH on bladder cancer. Whereas gross haematuria is considered an important sign of the presence of bladder cancer, the disease-predictive value of µH is less clear. No association of µH with the development of bladder tumours in a prospective screening cohort of chemical workers was observed. The positive predictive value of µH for bladder cancer was as low as 1.2%. Haematuria interfered with NMP22 but not with cytology and UroVysion(TM) test results.
  
  
  OBJECTIVE
  • To assess the positive predictive value (PPV) of microhaematuria (µH) and gross haematuria (GH) in bladder cancer screening and the influence of haematuria on tumour tests in a prospective study.
  
  
  METHODS
  • From September 2003 to January 2010, 1323 men took part in an annual voluntary bladder cancer screening programme for chemical workers with former exposure to aromatic amines. • In 5315 urine samples haematuria was determined with a dipstick, followed by a microscopic blood cell count in the sediment. Haematuria was categorized into traces, µH and GH. • Urinary leukocytes and other factors were investigated as potential predictors of haematuria using a generalized estimating equation model for repeated urinalysis. The risk of haematuria for positive tumour tests was analysed correspondingly. • The bladder cancer risk was estimated for the highest degree of haematuria occurring during the study with Poisson regression.
  
  
  RESULTS
  • As of July 2010, 15 bladder tumours were detected in 14 participants. • GH was found in four out of nine high-grade tumours and associated with a rate ratio of 3.82, 95% confidence interval (CI) 0.50-29.15 for the development of bladder lesions. • The PPV of GH was 11.4%, but only 1.2% for µH. µH occurred in 18.8% of urine samples and was not associated with bladder cancer [rate ratio (RR) 0.72, 95% CI 0.11-4.78]. • Abundant urinary leukocytes were associated with µH [odds ratio (OR) 8.34, 95% CI 2.26-30.69] and even stronger with GH (OR 22.25, 95% CI 6.42-77.06). • Haematuria and leukocytes influenced NMP22 positivity (µH: OR 1.63, 95% CI 1.06-2.51, abundant leukocytes: OR 8.90, 95% CI 1.58-50.16), but not test results for urine cytology and UroVysion(TM) .
  
  
  CONCLUSIONS
  • While the PPV of µH for bladder cancer was low, there was a strong influence of haematuria and leukocytes on the protein-based tumour test NMP22®. • Erythrocytes and leukocytes should be determined at least semi-quantitatively for the interpretation of positive NMP22 test results. • In addition, a panel of tumour tests that includes methods not affected by the presence of erythrocytes or leukocytes such as cytology and UroVysion(TM) would improve bladder cancer screening.
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum IPA, Bochum, Germany. pesch@ipa-dguv.de
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Michael
authors.initials: M
authors.lastname: Nasterlack
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Eberle
authors.forename: Nadine
authors.initials: N
authors.lastname: Bonberg
authors.forename: Dirk
authors.initials: D
authors.lastname: Taeger
authors.forename: Gabriele
authors.initials: G
authors.lastname: Leng
authors.forename: Gerhard
authors.initials: G
authors.lastname: Feil
authors.forename: Georg
authors.initials: G
authors.lastname: Johnen
authors.forename: Katta
authors.initials: K
authors.lastname: Ickstadt
authors.forename: Mattias
authors.initials: M
authors.lastname: Kluckert
authors.forename: Harald
authors.initials: H
authors.lastname: Wellhäusser
authors.forename: Arnllf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
mesh_terms: D000328:Adult; D000368:Aged; D000588:Amines / Q000633:toxicity*; D002617:Chemical Industry; D055088:Early Detection of Cancer / Q000379:methods*; D004912:Erythrocytes / Q000378:metabolism; D006417:Hematuria / Q000139:chemically induced / Q000175:diagnosis*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D016273:Occupational Exposure / Q000009:adverse effects*; D011446:Prospective Studies; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000175:diagnosis*
chemical_list: D000588:Amines; D009687:Nuclear Proteins; C100379:nuclear matrix protein 22