Nuclear matrix protein-22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study.

UNLABELLED: What's known on the subject? and What does the study add? The prognosis of bladder cancer significantly depends on tumour stage and time of diagnosis so early diagnosis is desirable to decrease mortality and treatment costs. The NMP22 test is approved for clinical application by the Food and Drug Administration (FDA) of the US. Previous studies have reported values of 47-100% for sensitivity and 58-91% for specificity with this test, but there is no new data on the predictive value of NMP22 for screening bladder cancer (BC). The most important risk factor for BC is the tobacco consumption but occupational exposure to carcinogenic substances, especially aromatic amines, is regarded as another risk factor. The UroScreen study is a prospective longitudinal study for the early detection of BC. To our knowledge, it is the largest prospective validation study conducted over the longest period of time. The study results led us to conclude that, based on the currently available data, NMP22 should not be regarded as an alternative to endoscopy, and we could not make a general recommendation for screening or follow-up. The UroScreen results indicate that urine-based molecular markers could be a suitable addition to urine cytology and the detection of microhaematuria. OBJECTIVE: To evaluate the value of nuclear matrix protein-22 (NMP22) in bladder cancer (BC) screening, and its effect on variables in a prospective study in a high-risk population. PATIENTS AND METHODS: A total of 1772 chemical workers (mean age 62 years) exposed to carcinogenic aromatic amines were enrolled in the study. In all, 7091 screening check-ups in 1609 subjects were performed. Urine samples were collected for a quantitative NMP22 immunoassay, urine analysis and creatinine concentration assessment. Cystoscopy and subsequent transurethral resection were performed where there were suspicious findings. RESULTS: Histopathological analysis found three papillary urothelial neoplasms of low malignant potential, five recurrent BCs and 13 primary BCs. Three tumours were at a muscle-invasive stage (pT2, pT3a or pT3b). We found higher NMP22 concentrations (>10 U/mL) in 224 patients, which correctly predicted BC in six cases (sensitivity 97.29%, specificity 28.57%; negative predictive value 99.04%, positive predictive value 12.24%). Gross haematuria affected NMP22 results (odd ratio [OR] 3.49, 95% confidence interval [CI] 1.81-6.73). Infection also affected NMP22 results (OR 4.13, 95% CI 2.31-7.35). NMP22 was more frequently positive in urine with creatinine concentration >2.5 g/L (OR 1.61, 95% CI 0.91-2.86). CONCLUSIONS: NMP22 outcomes are affected by haematuria, infection and concentrated urine. NMP22 alone cannot be recommended for primary screening in a high-risk population nor as an alternative to cystoscopy during follow-up. A NMP22 test might be a useful adjunct to urine cytology.

The relationship of SSRI and SNRI usage with interstitial lung disease and bronchiectasis in an elderly population: a case-control study.

BACKGROUND: The association between interstitial lung disease (ILD) and selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors (SSRI/SNRI) has been previously described in published case reports. However, its prevalence may be more common than expected. We examined the association between SSRI/SNRI usage and presence of ILD and or bronchiectasis (ILD/B) in an elderly population. METHODS: We conducted a retrospective case series and case-control study involving all 296 eligible elderly patients in one primary care geriatric practice in Victoria, BC, Canada. Cases required the presence of ILD/B on computed tomography (CT) or chest X-ray (CXR). Cases were excluded if they had other causes for ILD/B on CXR or CT such as exposure to known pneumotoxic drugs, metastatic cancer, rheumatoid lung disease, sarcoidosis, previous pulmonary tuberculosis, or pneumoconiosis. Data were abstracted from the patients' medical record. The exposure variable was standardized cumulative person-month (p-m) dose of SSRI/SNRI. The study was approved by the Clinical Research Ethics Board of University of British Columbia with a waiver of informed consent. RESULTS: A total of 12 cases and 273 controls were identified. Their mean ages were 89.0 and 88.7 years, respectively (p=0.862). A total of 10/12 cases and 99/273 controls were exposed to SSRI/SNRI. The odds ratio was 8.79, 95% confidence interval 2.40-32.23 (p=0.001). The median p-m exposure to SSRI/SNRI was 110.0 months for cases and 29.5 for controls (p=0.003). CONCLUSION: SSRIs and SNRIs were significantly associated with the risk of ILD/B in this elderly population. Because of their widespread usage, further studies should be done to validate these findings. Prescribers should cautiously monitor patients for development of insidious pulmonary symptoms when these drugs are used.