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

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METHODS: UroScreen is going to be conducted as extended screening program of annual preventive medical checkups for early diagnosis of bladder cancer in high-risk populations according to the guidelines of the German Social Accident Insurance. As of September 2009, 1,611 active and former chemical workers at the age of 58 (25-86) years formerly exposed to tumorigenic aromatic amines were enrolled. All subjects gave informed consent. 6,391 preventive medical checkups were performed. Urine samples were collected for urine cytology, chromosomal aberrations by the UroVysion test, and quantitative determination of nuclear matrix protein 22 (NMP22) by the quantitative NMP22 immunoassay. If ⱖ 1 test was positive (UroVysion ⬎ 3 polyploid cells, NMP22 ⬎ 10 U/ml), cystoscopy was recommended. Additionally, survivin was analyzed by an mRNA assay. The cut-off for a positive survivin test was ⬎ 40,000 copies. RESULTS: Among 1,611 persons enrolled in 6,391 annual investigations, 290 subjects revealed ⱖ 1 positive tumor marker test. Survivin was tested positive in 138 urine samples. Urine cytology, UroVysion, and NMP22, were positive in 5, 57, and 209 subjects, respectively. UroVysion in combination with cytology and/or NMP22 was positive in another 19 subjects. So far, cystoscopy was performed in 182 of these subjects on a voluntary basis. Nine bladder carcinomas (2 Cis, 3 pTa, 1 pT1, 1 pT1⫹Cis, 1 pT2, 1 pT3b) and 2 bladder papillomas were detected. Hematuria was diagnosed in 4 of these tumor patients only. Another 6 bladder cancers (3 pTa, 2 pT1, 1 pT1⫹Cis) and another papilloma were detected in subjects in whom cytology, UroVysion, and NMP22, respectively were negative. CONCLUSIONS: The interim results underline that tumor markers are a helpful tool in early diagnosis of bladder cancer in asymptomatic persons. Eleven of the 18 bladder tumors were detected only because of at least one positive tumor marker test. The combination of cell-based (UroVysion) and protein-based (NMP22) markers may improve sensitivity and specificity of urine-based tumor markers in screening high-risk populations for bladder cancer. Source of Funding: The study was supported by the Federation of German Accident Insurance Institutions (DGUV), St. Augustin, Germany, Abbott GmbH & Co. KG, Wiesbaden, Germany, Matritech GmbH, Freiburg, Germany, and Fujirebio Diagnostics Inc. (FDI), Malvern, PA, USA

1162 LONG-TERM USE OF SUPPLEMENTAL VITAMIN C, VITAMIN D AND VITAMIN E DOES NOT REDUCE THE RISK OF UROTHELIAL CELL CARCINOMA OF THE BLADDER IN THE VITAMINS AND LIFESTYLE STUDY James Hotaling*, Jonathan Wright, Gaia Pocobelli, Michael Porter, Emily White, Seattle, WA INTRODUCTION AND OBJECTIVES: Millions of Americans take vitamin supplements with Vitamin C, D and E as some of the most commonly used. The US literature on the chemopreventive role of these vitamins for urothelial cell carcinoma of the bladder (UC) is conflicting and is limited to retrospective study designs. Using the prospective VITamins And Lifestyle (VITAL) cohort study, we examine the association of supplemental Vitamin C, D and E use on risk of UC. METHODS: 77,719 residents of Washington State aged 50-76 years completed a baseline questionnaire in 2000-2002 on supplement use and cancer risk factors, and were followed prospectively via linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry through 2007 to obtain 330 incident TCC cases. Aggregate vitamin use over the previous 10 years was stratified into none and tertiles of 10-year average intake per day. Hazard ratios (HR) were estimated by multivariate Cox regression models controlling for age, gender, race, body mass index (BMI), fruit and vegetable intake and smoking status. RESULTS: In the age-adjusted model, increasing Vitamin D use was associated with a reduced risk of UC (pTrend ⫽ 0.03) with the highest tertiles of Vitamin D having a 23% risk reduction compared to non-users (HR 0.77 95% CI 0.59-1.0). Increasing usage of Vitamin C

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and Vitamin E were associated with a non-significant reduction of UC risk (both p ⬍ 0.09) with the higher tertile of each supplement having an approximately 25% risk reduction compared to non-users (HR for Vitamin C: 0.75 95% CI 0.56-1.0; HR for Vitamin E: 0.77 95%CI 0.57-1.0). However, in the multivariate models no significant chemopreventive effects for Vitamin C, D and E were observed (all pTrend ⬎ 0.48). CONCLUSIONS: This is the first prospective study based on an American population to examine the use of Vitamin C, D and E supplements and risk of UC. We found no significant effects of any of these vitamins on risk of UC. The apparent effects in the unadjusted model were largely explained by confounding factors in the adjusted model. This study suggests that future studies of chemoprevention in UC should be prospective and control for known confounders of UC. Source of Funding: NIH

1163 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, Wenjun Xiao, Shanghai, China, People’s Republic of 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.

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METHODS: Between 1995 and 2007, 153 patients were diagnosed with T1G3 bladder cancer at our institution. In 77 patients, initial TUR-BT was performed under PDD condition, and 76 patients underwent TUR-BT in a standard white light setting. PDD was performed either using 5-aminolevulinate or hexaminolevulinate for bladder instillation. Average follow-up was 53.9 months. Fisher’s exact test and Kaplan-Meier method were used to test data for significance. RESULTS: Of 77 patients who were treated using PDD at initial TUR-BT, recurrence occurred in 23 (29.9%) cases, whereas 43 of 76 (56.6%) patients treated without PDD showed a recurrence (p⬍0.001). In the PDD-group a deferred cystectomy due to tumor recurrence/ progression was performed in 15.4%. In the white-light group 30.8% underwent a deferred cystectomy (p⫽0.036). Median time to cystectomy in the PDD-group was two months compared to 11 months in the white light-group (p⬍0.001). A limitation of the present study is the retrospective, monocenter setting, which is more likely to be biased. CONCLUSIONS: PDD during initial TUR-BT in T1G3 bladder cancer significantly reduced the rate of recurrence in our study-population. The use of PDD was associated with a lower number of deferred cystectomies compared to the white light group. Therefore, the selection of patients who are suitable for a bladder-preserving approach was more feasible in patients who underwent initial TUR-BT under PDD conditions. PDD seems to be associated with superior initial tumor control and more effective tumor treatment also in patients with T1G3 bladder cancer. Source of Funding: None

1165 VARIANT HISTOLOGIC DIFFERENTIATION IN UROTHELIAL CARCINOMA IS FREQUENTLY UNDER-RECOGNIZED OR DOCUMENTED IN COMMUNITY PRACTICE Rajal Shah*, Lakshmi Kunju, Ann Arbor, MI

Source of Funding: None

1164 FLUORESCENCE ENDOSCOPY IN PATIENTS WITH T1G3 BLADDER CANCER – INFLUENCE ON RECURRENCE AND RATE OF DEFERRED CYSTECTOMIES Alexander Karl*, Peter Stanislaus, Dirk Zaak, Thomas Stadler, Stefan Trtischler, Munich, Germany; Ruth Knu¨chel, Aachen, Germany; Christian Stief, Munich, Germany INTRODUCTION AND OBJECTIVES: Therapeutic strategies on treatment of T1G3 urothelial cancer of the urinary bladder are dependent on multiple factors. This retrospective study was performed to investigate the impact of Photodynamic diagnosis (PDD) on recurrence rates and the performance of deferred cystectomies in patients with T1G3 bladder cancer.

INTRODUCTION AND OBJECTIVES: Urothelial carcinomas (UCs) have a peculiar capacity for “divergent” or “mixed histology” differentiation comprising of several unusual histologic variants, most of which have been recognized in the WHO 2004 classification. Recognition and documentation of these variants in the pathology report is critical as they have potential diagnostic, therapeutic and prognostic implications. Our aim was to assess the awareness and reporting practices of variant histologic differentiation in UCs amongst community pathologists. METHODS: All transurethral bladder tumor resections (TURBT) performed at outside institutions and reviewed at our institution prior to instituting therapy, were retrieved from the pathology database. UCs demonstrating divergent histologic differentiation diagnosed at our institution were selected and were compared with pathology reports sent by the referring community pathologists to assess the differences in documentation of divergent histology. Cases with pure squamous cell carcinoma, adenocarcinoma and sarcoma were excluded. Mixed histologic differentiation was quantitated as focal (1050%) and extensive (⬎50%). RESULTS: Of 589 TUBRT, 115 (19.5%) showed UC with divergent differentiation. Majority (88%) cases showed a single pattern while 12% showed multiple patterns of divergent differentiation. Overall, divergent differentiation was extensive in 55% cases. Squamous differentiation (32%) was most commonly seen followed by small cell (14%), glandular (13%), micropapillary (10%), nested (8%), sarcomatoid (6%), lymphoepithelial (3%) and plasmacytoid (2%) differentiation. Divergent differentiation was not documented initially by the contributing community pathologist in 44% (51) cases. Of these 51 cases, divergent histologic differentiation was focal in 57% and extensive in 43% cases. The histologic variants most likely to be under-recognized included lymphoepithelial and plasmacytoid types (100%), followed by micropapillary (86%), nested (75%) and small cell (42%) differentiation. Overall, squamous, sarcomatoid and glandular differentiation had good reporting correlation (¡Y´75%).