Detection Of Bladder Tumors Research Articles

Abstract 4023: Genome-wide analysis of CpG island methylation identified OTX1, OSR1 and ONECUT2 as biomarkers for recurrent bladder cancer detection in voided urine

Abstract Cancers of the urinary bladder (BC) present as muscle-invasive (MIBC) or non-muscle invasive (NMIBC). Major problems with NMIBC are that 70% of the tumors will recur and 10-20% will eventually progress to MIBC. Therefore the patients are monitored by cystoscopy every 3-6 months after transurethral resection of the tumor in order to spot potential recurrences. DNA methylation has been shown to contribute to the pathogenesis cancer and may serve as useful biomarker. Recent studies showed promising urine methylation biomarkers for BC, but none of these were specifically tested for detection of recurrent BCs which are often smaller and hence more difficult to detect than primary tumors. Therefore we aimed to develop an assay specific for the diagnosis of recurrent bladder tumors in voided urine. From our earlier genome-wide study, we selected 8 candidate CGIs (CpG islands) methylated in BC to screen for the detection of recurrent bladder tumors in voided urine. We first screened these 8 CGIs on an independent set of 50 FFPE bladder tumors and 70 urines from age matched individuals without any history of BC as controls using BS-SNaPshot (Bisulfite specific single nucleotide primer extension assay). Subsequently, the 8 CGIs were investigated in a test set of 100 preTUR (before Trans Urethral Resection) urines associated with a concomitant recurrent tumor. We analyzed the sensitivity, specificity, AUC (area under the curve), PPV and NPV of all the individual markers and five best combinations. We then validated this on a separate cohort of 100 preTUR urines samples. Single marker OTX1 identified recurrent bladder tumors in voided urine with a sensitivity of 71% at a specificity of 90% with an AUC of 0.85 (CI: 0.80-0.91, P<0.0001). A 3 gene methylation panel OTX1, ONECUT2 and OSR1 showed a sensitivity of 73% at a specificity of 90% with an AUC of 0.86 (CI: 0.80-0.91, P< 0.0001). Combining this 3-gene panel methylation assay with FGFR3 (fibroblast growth factor receptor 3) mutation assay achieved a sensitivity of 78% at a specificity of 90% with an AUC of 0.87 (CI: 0.82-0.93, P< 0.0001). This panel of markers showed a sensitivity of 100% in detecting bladder tumor tissue DNA. These markers were also investigated on 40 urines collected from patients who are recurrence free for a period of longer than 6 months. A total of 9/40 (22%) urines were positive in these recurrence free patients. The lower specificity of these samples could be due to the anticipatory effect that has been attributed to urine tests, i.e. urines test sees the tumor earlier than cystocopy. We also observed that multiple tumors from a patient are highly concordant in their methylation percentage, which underlines the usefulness of the markers. In summary the panel biomarkers that are identified will be able to detect the recurrent bladder tumors in voided urine, thereby helping in surveillance of patients with bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4023. doi:1538-7445.AM2012-4023

Detection of Urothelial Tumors: Comparison of Urothelial Phase with Excretory Phase CT Urography—A Prospective Study

To compare contrast material-enhanced computed tomographic (CT) urography 60 seconds after injection of contrast material (urothelial phase [UP]) after intravenous administration of a diuretic with the standard 5-minute delayed excretory phase (EP) in a high-risk population for upper tract tumors. Institutional review board approval and informed consent were obtained. Eighty CT urographic examinations in 77 patients known to have or at high risk for urothelial malignancy were included. After intravenous administration of a diuretic, dual-phase CT urography was performed at 60 seconds (UP) and 5 minutes (EP) after intravenous administration of contrast material. Two experienced abdominal radiologists independently interpreted each phase more than 1 month apart to minimize recall bias. Urinary tract distention and location and size of all lesions suspected of being urothelial tumors were recorded. Standard of reference was obtained from prospective study interpretation and surgical histopathologic findings. Generalized estimating equations for logistic regression were used to compare performance measures and adjust for the correlation of repeated measures within patients. There were 23 upper and 61 lower urinary tract tumors confirmed in 15 and 32 patients, respectively. For detection of bladder tumors, there was higher sensitivity for the UP than the EP (89.3% [109 of 122] vs 70.5% [86 of 122], respectively; P<.0001). For detection of upper tract tumors, there was higher sensitivity for the UP than the EP (82.6% [38 of 46] vs 69.6% [32 of 46], respectively; P=.0194). Distention of all upper urinary tract segments was better during the EP than the UP (P<.0001). UP CT urography after injection of a diuretic has a higher lesion detection rate than the EP for both upper and lower urinary tract tumors, which suggests its possible use as a single-phase protocol for evaluation of the entire urinary tract in patients at high risk for urothelial tumors.

Reply

There are 2 major issues related to the treatment of large bladder tumors: the often difficult to find small size satellite or concomitant lesion (usually Stage pTa and carcinoma in situ) and the sometimes challenging endoscopic removal of the large size tumor bulk. Editorial CommentUrologyVol. 79Issue 4PreviewUrologists are interested in improving the detection and transurethral resection (TUR) of nonmuscle-invasive bladder tumors. The aim is to achieve better staging, derive rational treatments, and improve local surgical control to reduce the frequency of tumor recurrence and disease progression. Toward this end, the authors have studied narrow band imaging (NBI) cystoscopy coupled with bipolar plasma vaporization (BPV) for large bladder tumors in a randomized clinical trial. Compared with conventional TUR using white light cystoscopy, the combined surgical method reduced the residual tumor detection on repeat TUR from 17.5% to 6.7% and the 1-year tumor recurrence rate from 17.8% to 7.9%. Full-Text PDF

440 CT cistography in the detection of bladder tumors: A new non-invasive technique?

440 CT cistography in the detection of bladder tumors: A new non-invasive technique?

Genome-wide Analysis of CpG Island Methylation in Bladder Cancer Identified TBX2, TBX3, GATA2, and ZIC4 as pTa-Specific Prognostic Markers

BackgroundDNA methylation markers could serve as useful biomarkers, both as markers for progression and for urine-based diagnostic assays. ObjectiveIdentify bladder cancer (BCa)–specific methylated DNA sequences for predicting pTa-specific progression and detecting BCa in voided urine. Design, setting, and participantsGenome-wide methylation analysis was performed on 44 bladder tumours using the Agilent 244K Human CpG Island Microarray (Agilent Technologies, Santa Clara, CA, USA). Validation was done using a custom Illumina 384-plex assay (Illumina, San Diego, CA, USA) in a retrospective group of 77 independent tumours. Markers for progression were identified in pTa (n=24) tumours and validated retrospectively in an independent series of 41 pTa tumours by the SNaPshot method (Applied Biosystems, Foster City, CA, USA). MeasurementsThe percentage of methylation in tumour and urine samples was used to identify markers for detection and related to the end point of progression to muscle-invasive disease with Kaplan-Meier models and multivariate analysis. Results and limitationsIn the validation set, methylation of the T-box 2 (TBX2), T-box 3 (TBX3), GATA binding protein 2 (GATA2), and Zic family member 4 (ZIC4) genes was associated with progression to muscle-invasive disease in pTa tumours (p=0.003). Methylation of TBX2 alone showed a sensitivity of 100%, a specificity of 80%, a positive predictive value of 78%, and a negative predictive value of 100%, with an area under the curve of 0.96 (p<0.0001) for predicting progression. Multivariate analysis showed that methylation of TBX3 and GATA2 are independent predictors of progression when compared to clinicopathologic variables (p=0.04 and p=0.03, respectively). The predictive accuracy improved by 23% by adding methylation of TBX2, TBX3, and GATA2 to the European Organisation for Research and Treatment of Cancer risk scores. We further identified and validated 110 CpG islands (CGIs) that are differentially methylated between tumour cells and control urine. The limitation of this study is the small number of patients analysed for testing and validating the prognostic markers. ConclusionsWe have identified four methylation markers that predict progression in pTa tumours, thereby allowing stratification of patients for personalised follow-up. In addition, we identified CGIs that will enable detection of bladder tumours in voided urine.

Bladder cancer imaging

To present the recent advances in imaging for diagnosis, staging, and follow-up of bladder cancer. The use of multidetector 64-slice computed tomography (CT) and diffusion-weighted imaging has enabled higher-resolution imaging of bladder cancer on CT and MRI, respectively, increasing both specificity and sensitivity in the detection of bladder tumors and extravesical disease relative standard imaging. Although urinary excretion of F-FDG produces difficulties in the interpretation of F-FDG PET/CT, new techniques have been described to overcome this limitation. The use of the agent C-acetate with PET/CT may be another option when performing imaging for staging and treatment decision-making. Accurate and reproducible imaging is critical in the management of bladder cancer. The resolution of a number of imaging modalities has increased, likely allowing for improved treatment decisions. Further research is needed to improve the diagnosis of small and/or flat lesions.

Detection of Bladder Cancer Using Novel DNA Methylation Biomarkers in Urine Sediments

Bladder cancer (BCa) remains a lethal malignancy that can be cured if detected early. DNA hypermethylation is a common epigenetic abnormality in cancer that may serve as a marker of disease activity. We selected 10 novel candidate genes from the most frequently hypermethylated genes detected by DNA microarray and bisulfite pyrosequencing of bladder cancers and applied them to detect bladder cancer in urine sediments. We analyzed DNA methylation in the candidate genes by quantitative methylation-specific real-time PCR (qMSP) to detect bladder cancer in urine sediments from 128 bladder cancer patients and 110 age-matched control subjects. Based on a multigene predictive model, we discovered 6 methylation markers (MYO3A, CA10, SOX11, NKX6-2, PENK, and DBC1) as most promising for detecting bladder cancer. A panel of 4 genes (MYO3A, CA10, NKX6-2, and DBC1 or SOX11) had 81% sensitivity and 97% specificity, whereas a panel of 5 genes (MYO3A, CA10, NKX6-2, DBC1, and SOX11 or PENK) had 85% sensitivity and 95% specificity for detection of bladder cancer (area under curve = 0.939). By analyzing the data by cancer invasiveness, detection rate was 47 of 58 (81%) in non-muscle invasive tumors (pTa, Tis, and pT1) and 62 of 70 (90%) in muscle invasive tumors (T2, T3, and T4). This biomarker panel analyzed by qMSP may help the early detection of bladder tumors in urine sediments with high accuracy. The panel of biomarker deserves validation in a large well-controlled prospectively collected sample set.

Volume-Based Features for Detection of Bladder Wall Abnormal Regions via MR Cystography

This paper proposes a framework for detecting the suspected abnormal region of the bladder wall via magnetic resonance (MR) cystography. Volume-based features are used. First, the bladder wall is divided into several layers, based on which a path from each voxel on the inner border to the outer border is found. By using the path length to measure the wall thickness and a bent rate (BR) term to measure the geometry property of the voxels on the inner border, the seed voxels representing the abnormalities on the inner border are determined. Then, by tracing the path from each seed, a weighted BR term is constructed to determine the suspected voxels, which are on the path and inside the bladder wall. All the suspected voxels are grouped together for the abnormal region. This work is significantly different from most of the previous computer-aided bladder tumor detection reports on two aspects. First of all, the T (1)-weighted MR images are used which give better image contrast and texture information for the bladder wall, comparing with the computed tomography images. Second, while most previous reports detected the abnormalities and indicated them on the reconstructed 3-D bladder model by surface rendering, we further determine the possible region of the abnormality inside the bladder wall. This study aims at a noninvasive procedure for bladder tumor detection and abnormal region delineation, which has the potential for further clinical analysis such as the invasion depth of the tumor and virtual cystoscopy diagnosis. Five datasets including two patients and three volunteers were used to test the presented method, all the tumors were detected by the method, and the overlap rates of the regions delineated by the computer against the experts were measured. The results demonstrated the potential of the method for detecting bladder wall abnormal regions via MR cystography.

Use of a MET-specific photoprobe to identify bladder tumors in an orthotopic xenograft model of bladder cancer.

260 Background: Met over-expression has been found in bladder cancer (CaB). Stage and grade increases in urothelial carcinoma have been found to correlate with increases in Met expression. To assess whether molecular optical imaging could enhance the detection of bladder tumors, we used a Met-specific soluble photoprobe in an orthotopic xenograft model of bladder transitional cell carcinoma (TCC). Methods: An orthotopic xenograft murine model of CaB was developed with T24-Luciferase-positive bladder cancer cells. Presence of tumor was confirmed by luciferase optical imaging (Xenogen IVIS) of mice, 4 weeks after TCC cell implantation. Mice were euthanized and their bladders removed and bivalved. Bladders were incubated for 30 minutes with unbound fluorophore (Cy5**, Peak emission at 675 nM) and subsequently for another 30 minutes with Cy5** bound to a Met-specific peptide. Fluorescence imaging (Maestro) was performed before and after each incubation period. Following imaging, presence of tumor was confirmed histologically. Results: Cy5**-Met- peptide bound in sufficient density to tumor tissue in bladders for visualization by optical imaging. The tumor to normal bladder imaging ratio ranged from 2:1 to 8:1. Bladder regions with high uptake of Cy5**-Met-peptide corresponded to tumor areas confirmed by histological analysis. Conclusions: Cy5**-Met-peptide successfully targets Met in an orthotopic xenograft model of bladder cancer. Our results suggest that this agent maybe useful for the enhanced visualization of bladder cancer tumors during cystoscopy. No significant financial relationships to disclose.

Incidence of bladder cancer in a one-stop clinic

The aim of this study is to demonstrate the importance of transvaginal scan (TVS) in the detection of bladder tumors in patients presenting with postmenopausal bleeding. We examined the case records of all patients that attended a one-stop clinic between September 2001 and May 2004. Those presenting with postmenopausal bleeding (PMB) underwent transvaginal scan and endometrial pipelle sampling. Where bladder pathology was detected, urine cytology was done before referral to the urologist. In all, 753 women were referred. There were 17 cases of endometrial cancer detected. Three cases of bladder tumor (malignant transitional cell cancer) were found. We recommend careful assessment of all pelvic organs in women presenting with PMB.

Accuracy and Factors Affecting the Outcome of Multi-Detector Computerized Tomography Urography for Bladder Tumors in the Clinical Setting

PurposeThe objective of this study was to investigate the diagnostic accuracy of multi-detector computerized tomography urography (MDCTU) for the detection of bladder tumors.Materials and MethodsWe retrospectively reviewed the medical records of 143 patients who were scanned by use of 64-channel MDCTU and who underwent cystoscopy due to painless hematuria or a clinical suspicion of bladder tumor. We examined the accuracy of MDCTU for the detection of bladder tumors by comparing the results obtained by MDCTU with those obtained by cystoscopy. The associations between tumor characteristics, frequency of transurethral resection (TUR), and bladder volume and detectability of bladder tumors on MDCTU were also analyzed.ResultsOf 143 patients, 50 patients had a history of urothelial carcinomas. In these patients, the sensitivity and specificity of MDCTU were 60.0% and 80.0%, respectively. In 93 patients without previous urothelial carcinomas, the sensitivity and specificity of MDCTU were 86.7% and 96.8%, respectively. Falsely diagnosed cases had a smaller distended bladder volume (p=0.014) and a smaller tumor size (p=0.022) than did true diagnosed cases. The false-negative rate increased when the bladder tumor was located at the bladder neck. In the univariate analysis, the tumor location, size, frequency of TUR, bladder volume, and initial hematuria were associated with detectability by MDCTU (p<0.05).ConclusionsTo improve the accuracy of MDCTU for diagnosing bladder tumors, bladder filling is recommended. Thus, cystoscopy should be considered as a standard diagnostic tool for bladder tumors even in patients with normal MDCTU results, especially in the evaluation of recurrent, bladder neck-located, small, or sessile bladder tumors.

Performance of nuclear matrix protein 22 urine marker and voided urine cytology in the detection of urinary bladder tumors

Cystoscopy with urinary cytology is the gold standard for the diagnosis and follow-up of patients with tumors of the urinary bladder. The aim of the study was to evaluate the performance of the nuclear matrix protein 22 (NMP22) tumor marker test, BladderChek® point-of-care test and voided urinary cytology for the detection and follow-up of bladder tumors. NMP22 was measured using an ELISA assay in stabilized voided urine and using the BladderChek® test. Voided urinary cytology was performed on urine samples. Results were compared to cystoscopic findings and histopathological examination results after transurethral resection of the bladder lesion. For the prediction of malignant histopathological result, sensitivity and specificity were 45.2% and 75.0%, respectively, for NMP22 at a cut-off of 7.5 kU/L, 17.7% and 100% for the BladderChek® test and 37.0% and 100% for voided urine cytology. For the prediction of suspicious or positive cystoscopic finding, sensitivity and specificity were 40.4% and 72.1%, respectively, for NMP22 at a cut-off of 7.5 kU/L, 14.8% and 93.8% for the BladderChek® test and 26.8% and 98.1% for voided urine cytology. The NMP22 quantitative test showed higher sensitivity and lower specificity compared with voided urine cytology, whereas the sensitivity of the BladderChek® test was low. We could not recommend any of the three non-invasive tests as a replacement for cystoscopy for the diagnosis or follow-up of urinary bladder tumors.

Le diagnostic photodynamique (cystoscopie avec hexaminolévulinate) dans la surveillance des lesions urothéliales traitées de façon conservative

Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence.To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence.This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non–muscle-invasive bladder cancer (NMIBC).A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy.We studied the detection of NMIBC (intention to treat [ITT]: n = 831; six studies) and recurrence (per protocol: n = 634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection.BL cystoscopy detected significantly more Ta tumours (14.7%; p < 0.001; odds ratio [OR]: 4.898; 95% CI, 1.937–12.390) and CIS lesions (40.8%; p < 0.001; OR: 12.372; 95% CI, 6.343–24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p < 0.001), significant also in patients with primary (20.7%; p < 0.001) and recurrent cancer (27.7%; p < 0.001), and in patients at high risk (27.0%; p < 0.001) and intermediate risk (35.7%; p = 0.004). In 26.7% of patients, CIS was detected only by BL (p < 0.001) and was also significant in patients with primary (28.0%; p < 0.001) and recurrent cancer (25.0%; p < 0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p = 0.006; RR: 0.761 [0.627–0.924]), and lower in patients with T1 or CIS (p = 0.052; RR: 0.696 [0.482–1.003]), Ta (p = 0.040; RR: 0.804 [0.653–0.991]), and in high-risk (p = 0.050) and low-risk (p = 0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used.This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9–12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

Evaluation of Narrow-Band Imaging as a Complementary Method for the Detection of Bladder Cancer

We evaluated the use of narrow-band imaging (NBI) cystoscopy for the detection of bladder cancer and analyzed its diagnostic efficacy in cases of carcinoma in situ (CIS) and in cases with known urine cytology results. A prospective controlled study of NBI was conducted in 104 consecutive patients with definite or suspected bladder cancer. Transurethral targeted biopsies were performed after white light imaging (WLI) and NBI cystoscopy, and the histologic outcomes were compared. A total of 313 biopsies were taken, including 161 from sites identified as potentially abnormal by NBI and/or WLI cystoscopy, and 152 from apparently normal sites. The percentage of malignancies in the sites identified only by NBI was 55.7% (39/70 places). In 26.9% of patients (28/104), bladder tumors were detected only by NBI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio of a negative test (NLR) for the detection of bladder tumors using NBI in all patients were 92.7%, 70.9%, 63.4%, 94.7%, and 0.10, respectively. The sensitivity, specificity, PPV, NPV, and NLR for the detection of CIS using NBI were 89.7%, 74.5%, 78.8%, 87.2%, and 0.14, respectively. The sensitivity, specificity, PPV, NPV, and NLR for the detection of bladder tumors using NBI in patients with positive vs negative urine cytology were 85.4% vs 98.4%, 75.7% vs 66.3%, 61.2% vs 64.5%, 92.0% vs 98.5%, and 0.19 vs 0.02, respectively. NBI is a simple and effective method for identifying bladder tumors including CIS without the need for dyes because of its high sensitivity, high NPV, and low NLR.

Narrow-band imaging flexible cystoscopy in the detection of bladder urothelial cell carcionma

Objective To study the sensitivity and specifity for detection of bladder tumor by Narrow-band imaging flexible cystoscopy compared with WLI flexible systoscopy. Methods Between February 2009 and July 2009, NBI flexible cystoscopy and conventional WLI flexible cystoscopy with the same instrument (Olympus Exera Ⅱ endoscopy system) were both performed on 31 patients highly suspect of bladder neoplasm with same observed time and in a randomized sequenced paradigm. Every suspect mucosa lesion was biopsied in both NBI and WLI image to compare the diagnostic accuracy between them. Results Twenty-eight patients(90%) were pathologically bladder urothelial cell carcinoma (UCC). Of 28 patients 3 were Tis, 15 were Ta, 7 were T1, and 3 were T2. Twenty were low grade carcinom, 8 were high grade carcinoma and 16 had multiple tumors, 12 had a single tumor.Of 73 biopsied lesions, 61 were diagnosed UCC under WLI image with 84% sensitivity, while 80 of 91 diagnosed under NBI image with 88% sensitivity. WLI detected 23 patients with bladder UCC while NBI detected all 28 patients. NBI detected 19 additional UCC lesions in 15 of 28 patients, as compared with WLI(P＜0. 05). Conclusion NBI flexible cystoscopy can detect more bladder urothelial cell carcinoma than WLI flexible cystoscopy. Key words: Bladder neoplasms; Narrow-band image; Fexible cystoscopy

Abstract 4908: Detection of bladder tumor by quantitative methylation specific real time PCR from urine sediment DNA

Abstract Bladder cancer is the fifth most frequent human cancer and causes approximately 3% of all cancer-related deaths. DNA hypermethylation is a common epigenetic abnormality in cancer and may serve as a useful marker to clone new cancer-related genes as well as a marker of the disease activity. Recently, we developed a high throughput genome wide methylation assay, Methylated CpG Island Amplification Microarray (MCAM). Using MCAM, we investigated methylation changes in about 8,000 genes in bladder tumors. Through this screening method and validation by bisulfite pyrosequencing, we have developed novel biomarkers for diagnosis and prognosis of bladder tumor. We characterized a group of genes that was found to be methylated in 80-90% of the tested bladder tumor samples. These candidate genes (DBC1, MYO3A, SOX11, SLC16A12, NPTX2, NKX6-2, A2BP1, PENK and CA10) were used to screen for bladder cancer in urine samples by quantitative methylation specific real time PCR, thus representing a non-invasive method for early detection. Based on these data, we established a panel of 6 biomarkers (MYO3A, SOX11, NKX6-2, PENK, CA10 and quantity of DNA in test urine) that can be used for bladder tumor screening in urine samples. The method showed 89.1 % sensitivity and 91.4 % specificity for detection of bladder tumor urines (n=128) compared to normal control urine (n=105) by 3 or more than 3 positive out of 6 biomarkers. Analyzing by stage of bladder tumors, 5 out of 5 (100 %) in Tis, 21 out of 29 (72 %) in Ta, 18 out of 19 (95 %) in T1, 57 out of 60 (95 %) in T2, 6 out of 6 (100 %) in T3 and 2 out of 2 (100 %) in T4 showed 3 or more than 3 positive out of 6 biomarkers. Thus, 83% of Tis-Ta-T1 stages and 95.6 % of T2-T3-T4 stages were detected in analyzed bladder tumor urines. This DNA methylation biomarkers panel will help the early detection and monitoring of bladder tumor patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4908.

2019 PERFORMANCE OF COMPUTED TOMOGRAPHIC UROGRAPHY FOR THE DETECTION OF BLADDER TUMORS IN PATIENTS EVALUATED FOR MICROSCOPIC HEMATURIA

You have accessJournal of UrologyImaging/Radiology: Uroradiology I1 Apr 20102019 PERFORMANCE OF COMPUTED TOMOGRAPHIC UROGRAPHY FOR THE DETECTION OF BLADDER TUMORS IN PATIENTS EVALUATED FOR MICROSCOPIC HEMATURIA Bernardo Aguilar-Davidov, Jose Arturo Ramirez-Muciño, Mariano Sotomayor, Ricardo Castillejos-Molina, Guillermo Feria-Bernal, and Francisco Rodriguez-Covarrubias Bernardo Aguilar-DavidovBernardo Aguilar-Davidov More articles by this author , Jose Arturo Ramirez-MuciñoJose Arturo Ramirez-Muciño More articles by this author , Mariano SotomayorMariano Sotomayor More articles by this author , Ricardo Castillejos-MolinaRicardo Castillejos-Molina More articles by this author , Guillermo Feria-BernalGuillermo Feria-Bernal More articles by this author , and Francisco Rodriguez-CovarrubiasFrancisco Rodriguez-Covarrubias More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2052AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The prevalence of microscopic hematuria varies from 0.19% to 21% depending on the studied population. In patients without risk factors for primary renal disease, a complete urologic evaluation should be performed, and this includes imaging of the upper urinary tract followed by cystoscopic examination. Nevertheless, this recommendation was established before the widespread use of computed tomographic urography (CTU), which seems to provide accurate information of the urinary tract anatomy including the bladder. Some authors report very high performance of CTU making controversial the need of cystoscopy. Our objective was to evaluate the sensitivity, specificity, predictive value, and accuracy of CTU for the detection of bladder tumors in patients with microscopic hematuria. METHODS Institutional review board approval was obtained for this retrospective review of medical records of patients with microscopic hematuria initially evaluated with CTU and cystoscopy afterwards from January 2006 to April 2009. Patients with history of macroscopic hematuria in the last year or with urinary tract infection were excluded. A total of 101 patients were eligible for analysis. Official radiologist report of CTU detecting a bladder lesion suspicious of malignancy was considered positive. Since cystoscopy is the gold standard for the evaluation of bladder pathology, this study was considered the control. Cystoscopy was classified as positive when a lesion requiring biopsy or resection was found. Performance characteristics of CTU were determined by using the cystoscopic findings. RESULTS There were three CTU positive reports, two of which were confirmed by cystoscopy (true positive). In 3 additional patients CTU failed to detect a bladder tumor. The histologic report was transitional cell carcinoma in 3 patients, 1 papilloma, and 1 malacoplakia. Based on these results the CTU sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for bladder tumor detection is 40%, 99%, 67%, 97%, and 96%. CONCLUSIONS Although CTU has a high specificity, its sensitivity is limited. For this reason conventional cystoscopy should be considered the standard for the initial evaluation for patients with microscopic hematuria. Mexico City, Mexico© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e783 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bernardo Aguilar-Davidov More articles by this author Jose Arturo Ramirez-Muciño More articles by this author Mariano Sotomayor More articles by this author Ricardo Castillejos-Molina More articles by this author Guillermo Feria-Bernal More articles by this author Francisco Rodriguez-Covarrubias More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1163 NARROW-BAND IMAGING FLEXIBLE CYSTOSCOPY IN THE DETECTION OF NEW NON-MUSCLE INVASIVE BLADDER CANCER: A RANDOMIZED STUDY

You have accessJournal of UrologyBladder Cancer: Detection and Screening1 Apr 20101163 NARROW-BAND IMAGING FLEXIBLE CYSTOSCOPY IN THE DETECTION OF NEW NON-MUSCLE INVASIVE BLADDER CANCER: A RANDOMIZED STUDY Yijun Shen, Yiping Zhu, Dingwei Ye, Xudong Yao, Shilin Zhang, Bo Dai, Hailiang Zhang, Yao Zhu, Guohai Shi, Chunguang Ma, and Wenjun Xiao Yijun ShenYijun Shen More articles by this author , Yiping ZhuYiping Zhu More articles by this author , Dingwei YeDingwei Ye More articles by this author , Xudong YaoXudong Yao More articles by this author , Shilin ZhangShilin Zhang More articles by this author , Bo DaiBo Dai More articles by this author , Hailiang ZhangHailiang Zhang More articles by this author , Yao ZhuYao Zhu More articles by this author , Guohai ShiGuohai Shi More articles by this author , Chunguang MaChunguang Ma More articles by this author , and Wenjun XiaoWenjun Xiao More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.663AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Narrow-band imaging(NBI) is an optical image enhancement technique to enhance the contrast between mucosal surfaces and microvascular structures without dyes. Although it is now frequently used in gastrointestinal endoscopy, there are still some controversies about its benefit in the detection of urinary bladder cancer. One of the limitations of previous study is the possible observer bias as white-light imaging (WLI) and NBI were performed subsequently by the same urologist. This study was designed to investigate the detection rate of new non-muscle invasive bladder cancer(NIMBC) between NBI and WLI flexible cystoscopy with a randomized image sequential paradigm. METHODS Between February 2009 and October 2009, NBI and WLI flexible cystoscopy with the same instrument (Olympus Lucera sequential endoscopy system)were both performed on 45 patients with suspected new NIMBC in a randomized image sequential paradigm with the same observing time to avoid the observer bias. Biopsies obtained by NBI and WLI were examined separately for pathology. After biopsy, a standard TUR with resected samples was performed to show presence of tumors or not. RESULTS 41 patients (91.1%) were pathologically NIMBC. Of these 22 were Ta, 14 were T1, 5 were Tis. 89 Of 110 biopsied lesions were found tumor under WLI while 113 of 142 were under NBI. The sensitivity of WLI vs NBI for detecting bladder tumors in all 45 patients was 80.5% vs 97.6% (P<0.05), the specificity 50% vs 75% (P<0.05), the accuracy 77.8% vs 95.6% (P<0.05), and the AUC was 0.652 vs 0.863(P>0.05). All 5 Tis were detected by NBI while 2 missed by WLI. NBI detected 24 additional cancer lesions in 15 of 41 patients, as compared with WLI (P<0.05). CONCLUSIONS NBI flexible cystoscopy improved the detection of NIMBC over standard WLI cystoscopy, contributing to its high value in the clinical practice of bladder cancer. Shanghai, People's Republic of China© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e450-e451 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yijun Shen More articles by this author Yiping Zhu More articles by this author Dingwei Ye More articles by this author Xudong Yao More articles by this author Shilin Zhang More articles by this author Bo Dai More articles by this author Hailiang Zhang More articles by this author Yao Zhu More articles by this author Guohai Shi More articles by this author Chunguang Ma More articles by this author Wenjun Xiao More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Molecular screening for bladder cancer: progress and potential

Carcinoma of the urinary bladder is a common malignancy and a major cause of morbidity and mortality in the western world. Current understanding of etiology, disease process, molecular characteristics and management principles make urothelial carcinoma an ideal candidate for screening. The capacity of traditional noninvasive diagnostic procedures such as microhematuria testing and urine cytology to be used as stand-alone screening techniques is limited, however. New qualitative and quantitative molecular screening modalities can detect cellular and subcellular alterations that are often exclusively associated with urothelial carcinoma. Such alterations can be detected in a noninvasive manner, using urine as a marker source, with reasonable sensitivity and specificity. Application of several molecular assays in conjunction with traditional screening methods has had promising results. We propose an evidence-based and risk-based approach to future bladder cancer screening. Such an approach would harness the reasonable sensitivity, ease of use and cost-effectiveness of microhematuria testing, plus the specificity of molecular tests, to target high-risk populations for screening. The ultimate goals are to identify susceptible individuals, detect bladder tumors before they invade using unobtrusive and cost-effective methods, and optimize surveillance strategies for long-term follow-up.

Photodynamic Diagnosis (5-Aminolevulinic Acid) of Transitional Cell Carcinoma After Bacillus Calmette-Guérin Immunotherapy and Mitomycin C Intravesical Therapy

BackgroundPhotodynamic diagnosis (PDD) is a technique that enhances the detection of occult bladder tumors during cystoscopy using a fluorescent dye. ObjectiveTo study the differential effects of bacillus Calmette-Guérin (BCG) and mitomycin C (MMC) intravesical therapy on the false-positive rate of PDD of bladder cancer. Design, setting, and participantsThis study included 552 procedures and 1874 biopsies. InterventionTumors were resected and biopsies were taken from suspicious areas, under guidance of white-light endoscopy and 5-ALA (5-aminolevulinic acid)–induced fluorescence cystoscopy. MeasurementsThe influence of intravesical BCG immunotherapy and intravesical MMC chemotherapy on pyuria, inflammation, and PDD specificity was examined in univariate analyses. Results and limitationsBCG significantly results in inflammation (odds ratio [OR]: 1.53, p=0.002), leukocyturia (OR: 1.84, p=0.034), and false positives in PDD (OR: 1.49, p=0.001). However, a single BCG instillation within 3 mo before PDD is most likely not associated with increased false-positive rates (OR: 0.35, p=0.26). Leukocyturia normalizes within 6 wk after the last BCG instillation, but PDD specificity is reduced up to 3 mo. ConclusionsBCG is an important predictor for false positives in PDD (5-ALA). More than one BCG instillation within 3 mo before fluorescence cystoscopy decreases the specificity of PDD.