***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND Accumulating evidence suggests that DNA methylation markers could serve as sensitive and specific cancer biomarkers . OBJECTIVE To determine whether a panel of methylated genes would have the potential to identify primary bladder cancer ( BCa ) in voided urine sample s. DESIGN , SETTING , AND PARTICIPANTS A pharmacologic unmasking reexpression analysis in BCa cell lines was initially undertaken to unveil c and i date methylated genes , which were then evaluated in methylation-specific polymerase chain reaction ( MSP ) assays performed on DNA extracted from noncancerous and cancerous bladder tissues . The most frequently methylated genes in cancerous tissues , with 100 % specificity , were retained for subsequent MSP analysis in DNA extracted from urine sample s to build and vali date a panel of potential methylated gene markers . Urine sample s were prospect ively collected at three urologic centres from patients with histologically proven BCa and processed for use in real-time MSP and cytologic analysis .  Patients with nonmalignant urologic disorders were included as controls . MEASUREMENTS A urine sample was classified as valid when > or = 10 copies of the gene encoding ß-actin were measured in the urine sediment genomic DNA . Sensitivity , specificity , and predictive values of the MSP and cytology tests were assessed and compared . RESULTS AND LIMITATIONS MSP assays performed on 466 of the 496 ( 94 % ) valid urine sample s identified two genes , TWIST1 and NID2 , that were frequently methylated in urine sample s collected from BCa patients , including those with early-stage and low- grade disease . The sensitivity of this two-gene panel ( 90 % ) was significantly better than that of cytology ( 48 % ) , with comparable specificity ( 93 % and 96 % , respectively ) . The positive predictive value and negative predictive value of the two-gene panel was 86 % and 95 % , respectively . CONCLUSIONS Detection of the methylated TWIST1 and NID2 genes in urine sediments using MSP provides a highly ( > or = 90 % ) sensitive and specific , noninvasive approach for detecting primary BCa . TRIAL REGISTRATION BlCa-001 study - EudraCt 2006 - 003303 - 40 Objective : To compare the BTA statTM test ( BTA stat ) , a new one-step immunochromatographic assay that can be performed in the urologist ’s office or in the laboratory , to voided urine cytology and bladder wash cytology ( cytology ) in the diagnosis and monitoring of cancer of the bladder ( BC ) . Methods : BTA stat and cytology were performed in a double-blinded , prospect i ve , clinical study on specimens from 240 subjects ( 68 females ; mean age of subjects : 64 years ) suspected of having BC . Results : In 107 subjects with final diagnoses of BC confirmed by cystoscopy or cystoscopy and biopsy  , the overall sensitivities of BTA stat and cytology were 65 and 33 % , respectively . For tumor grade s I , II , and III , the sensitivities of BTA stat were 39 , 67 and 83 % , respectively . Those of cytology were 4 , 20 and 69 % . Nine subjects had a diagnosis of ‘ suspicious for bladder cancer ’ . The specificities of BTA stat and cytology  in the 124 subjects without BC were 64 and 99 % , respectively . In the subjects with a history of BC ( n = 74 ) , the specificities of BTA stat and cytology  were 72 and 99 % , respectively . The specificity of BTA stat was lower in subjects with benign or malignant genitourinary disease other than BC ( 46 % ) than in subjects without genitourinary disease ( 71 % ) . Conclusions : The BTA stat test  is considerably more sensitive than  cytology  in the detection of BC and can replace cytology as an adjunct to cystoscopy in the diagnosis and follow-up of patients with BC . However , due to low specificity , BTA stat should not be used without first ruling out potential interferences such as infections , renal disease and cancer , or genitourinary trauma There are no reliable serologic tumor markers for transitional cell carcinoma ( TCC ) of the urinary bladder and noninvasive urine investigations are inadequate . We used fluorescent microsatellite analysis ( MSA ) to detect serum DNA and urine‐sediment DNA alterations in patients with bladder cancer and prospect ively collected fresh tumor , peripheral blood , serum and spontaneous urine specimens from 39 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA . Fluorescent MSA was performed with 17 polymorphic markers from the chromosomal regions 5q , 8p , 9p , 9q , 13q , 14q , 17p , 17q and 20q in the 39 cancer patients and in 10 healthy controls . Serum DNA alterations were identified in 84.5 % ( 33 of 39 patients ) and tumor‐specific urine DNA alterations indicating the diagnosis were present in 72 % ( 27 of 39 patients ) of cases . None of the healthy controls displayed serum DNA alterations . The highest frequency of serum DNA aberrations ( 56 % ) was detected for chromosomal region 8p . The most frequent alterations in urine‐sediment DNA , 36 % and 26 % , were detected in chromosomal regions 8p and 9p , respectively . Identification of serum DNA and urine‐sediment DNA alterations was not related to stage of disease or grade of tumor ( p > 0.05 ) . Thus , MSA offers a highly sensitive and specific method for serum‐ and urine‐bound diagnosis of bladder TCC . © 2001 Wiley‐Liss , Objectives This study was carried out as a prospect i ve pilot study to evaluate the potential of  survivin mRNA measurement in patients suspicious for urothelial bladder cancer ( BC ) . Data were also analyzed for possible influences of secondary urological findings on survivin measurements . Methods  Survivin  was measured by an mRNA assay in voided urine sample s of 50 patients with suspicion of new or recurrent BC prior to transurethral resection .  Sample evaluation was possible in 49 cases . Histopathology revealed no malignancy in 17 ( 35 % ) and BC in 32 ( 65 % ) patients .  Survivin mRNA  was quantitated by real-time PCR from frozen cell pellets of centrifuged urine sample s. A ROC analysis of the survivin data was performed . Results ROC analysis identified the best cut-off level at 10,000 mRNA copies , result ing in a sensitivity of 53 % and a specificity of 88 % . Seven of the 20 pTa tumors ( 35 % ) , all four pT1 ( 100 % ) and all four muscle-invasive tumors ( 100 % ) were detected . Of four patients with carcinoma in situ ( Cis ) , 50 % could be identified . Only two patients ( 4 % ) were assessed as false positive . Histologically confirmed cystitis and concomitant urological findings ( inflammatory cells in urine , microhematuria and others ) had no detectable influence on survivin measurements . Conclusion In present group of patients , survivin was a reliable biomarker for high- grade urothelial BC ( sensitivity 83 % ) , but not for low grade ( sensitivity 35 % ) urothelial BC with a high specificity ( 88 % ) . No confounders influencing the results of survivin measurements could be identified BACKGROUND Human complement factor H-related protein ( hCFHrp ) is produced by several bladder cancer cell lines and may be useful as a cancer marker . The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs , symptoms , or preliminary test results . METHODS The BTA TRAK assay , a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine , was compared with exfoliative cytology in 220 patients ( 155 men , 65 women ; mean age , 64.2 years ) presenting with signs , symptoms , or preliminary diagnostic results suggestive of this disease .  Cystoscopy was the st and ard of detection . RESULTS In the 100 patients found to have bladder cancer , the overall sensitivities of the BTA TRAK assay ( at a previously determined decision threshold of 14 kilounits/L ) and cytology were 66 % ( 66 of 100 ) and 33 % ( 33 of 100 ) , respectively ( P < 0.001 ) . The BTA TRAK assay proved to be statistically more sensitive than cytology for tumor grade s I and II and for stage Ta and T1 tumors . In contrast , the overall specificity of the BTA TRAK assay in the 120 patients without cystoscopically confirmed bladder cancer was 69 % ( 83 of 120 ) and that of cytology was 99 % ( 119 of 120 ; P < 0.001 ) . The specificity of the BTA TRAK assay  was higher in patients without benign or malignant genitourinary disease other than bladder cancer ( 76 % ; n = 89 ) than in patients with these conditions . When the BTA TRAK assay and cytology were used together such that a positive result in either test was scored as positive and the results compared with those of the BTA TRAK assay alone , increases in overall sensitivity and equivalent specificity were observed . CONCLUSION Because of its relatively high sensitivity , the BTA TRAK assay could complement cytology as an adjunct to cystoscopy in the diagnosis and follow-up of most patients with bladder cancer The aim of our study was to prospect ively evaluate the potential diagnostic value and clinical applicability of quantitative analysis of telomerase subunits gene expression in urine for noninvasive detection of bladder cancer .  Expression levels of human telomerase reverse transcriptase ( hTERT ) and human telomerase RNA ( hTR )  were analyzed by real‐time reverse transcriptase polymerase chain reaction ( RT‐PCR ) in urine sample s from 163 subjects with bladder cancer and 237 controls ( 163 individuals with benign genitourinary diseases ; 74 healthy subjects ) . The sensitivity , specificity and optimal cutoffs were determined and compared to the corresponding values obtained by voided urine cytology . Quantitative urinary hTR analysis detects bladder cancer with an overall sensitivity of 77.0 % , whereas hTERT analysis reached a sensitivity of 55.2 % . The majority of undetected tumors were small , low‐ grade pTa lesions . Both hTR and hTERT  proved to be significantly more sensitive than cytology ( 34.5 % ; p < 0.001 ) . Specificities for hTR , hTERT and cytology  were 72.1 % , 85.0 % and 92.7 % , respectively , in the total study population and 96.9 % , 89.2 % and 100 % , respectively , in healthy subjects . Higher diagnostic accuracy was achieved by hTR than by hTERT analysis ( p < 0.05 ) . The specificity of hTR  increased to 85.0 % in the total population if urinary leukocyte contamination was excluded . These data suggest that quantitative hTR analysis is the most accurate telomerase‐based test for bladder cancer detection and has the potential to replace cytology as a noninvasive biomarker for disease diagnosis and follow‐up . © 2005 Wiley‐Liss , PURPOSE The limitations of cytology and the invasiveness of cystoscopy for detecting bladder cancer generate increasing interest in noninvasive , urine bound diagnostic tools . We assessed the diagnostic value of the newly developed immunocytochemical test , Immunocyt , which detects cellular markers specific for transitional cell cancer in the voided urine of patients with bladder cancer . MATERIAL S AND METHODS Participating in our prospect i ve study were 264 consecutive patients with a mean age of 65.9 years , including 114 in whom symptoms were suggestive of bladder cancer and 150 who were being followed after complete transurethral resection of superficial transitional cell carcinoma . Voided urine specimens were evaluated by  st and ard cytology and the Immunocyt test , which traces the monoclonal antibodies M344 , LDQ10 and 19A211 against transitional cell carcinoma in exfoliated urothelial cells . In all cases cystoscopy was subsequently performed and any suspicious lesion was evaluated by biopsy . RESULTS Histologically proved  transitional  cell carcinoma was found in 79 patients .  Immunocyt  with cytology had 89.9 % sensitivity overall ( 84 , 88 and 96.5 % in grade s 1 to 3 disease , respectively ) . A total of 34 ( 43 % ) , 3 ( 3.8 % ) and 34 ( 43 % ) cases were positive on Immunocyt only , cytology only and both evaluations , respectively . In 8 cases ( 10.1 % ) both tests were negative . Overall  Immunocyt  only was 86.1 % sensitive ( 84 , 84 and 89.6 % in grade s 1 to 3 disease , respectively ) and 79.4 % specific . Overall cyt 
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EVIDENCE SYNTHESIS Although different studies have shown the superiority of urine markers regarding sensitivity for bladder cancer detection as compared with cytology , none of these tests is ideal and can be recommended unrestrictedly .
Urine markers have been studied extensively to help diagnose bladder cancer and thereby decrease the need for cystoscopy .
However , no marker is available at present that can sufficiently warrant this .
Several urinary markers have higher but still insufficient sensitivity compared with cytology .
Urinary cytology or markers can not safely replace cystoscopy in this setting .