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PDF file - 68KB, Spearman correlation of DNA methylation levels of each marker in urine sediment samples of TURBT patients.

Purpose: The high risk of recurrence after transurethral resection of bladder tumor of nonmuscle invasive disease requires lifelong treatment and surveillance. Changes in DNA methylation are chemically stable, occur early during tumorigenesis, and can be quantified in bladder tumors and in cells shed into the urine. Some urine markers have been used to help detect bladder tumors; however, their use in longitudinal tumor recurrence surveillance has yet to be established.Experimental Design: We analyzed the DNA methylation levels of six markers in 368 urine sediment samples serially collected from 90 patients with noninvasive urothelial carcinoma (Tis, Ta, T1; grade low-high). The optimum marker combination was identified using logistic regression with 5-fold cross-validation, and validated in separate samples.Results: A panel of three markers discriminated between patients with and without recurrence with the area under the curve of 0.90 [95% confidence interval (CI), 0.86–0.92] and 0.95 (95% CI, 0.90–1.00), sensitivity and specificity of 86%/89% (95% CI, 74%–99% and 81%–97%) and 80%/97% (95% CI, 60%–96% and 91%–100%) in the testing and validation sets, respectively. The three-marker DNA methylation test reliably predicted tumor recurrence in 80% of patients superior to cytology (35%) and cystoscopy (15%) while accurately forecasting no recurrence in 74% of patients that scored negative in the test.Conclusions: Given their superior sensitivity and specificity in urine sediments, a combination of hyper- and hypomethylated markers may help avoid unnecessary invasive exams and reveal the importance of DNA methylation in bladder tumorigenesis. Clin Cancer Res; 20(7); 1978–89. ©2014 AACR.

PDF file - 125KB, Primer sequences used in pyrosequencing.

Spearman correlation of DNA methylation levels of each marker in urine sediment samples of TURBT patients.

Association between the score from the three-marker signature and the recurrent bladder tumor pathological characteristics of 34 recurrence patients.

PDF file - 76KB, DNA methylation status in urine sediment samples of TURBT patients at the time of first recurrence and the last follow-up visit of no recurrence patients.

Supplementary Figure Legends

PDF file - 97KB, Receiver operating characteristic (ROC) curves of the three-marker signature in detecting tumor recurrence.

PDF file - 68KB

PDF file - 88KB, DNA methylation alterations can be detected in urine sediment samples from patients with bladder cancer.

PDF file - 68KB, Association between the score from the three-marker signature and the primary bladder tumor pathological characteristics of 90 TURBT patients.

PDF file - 348KB, Three DNA methylation markers help predict the risk of recurrence of bladder tumors in urine sediments.

PDF file - 67KB, Association between the score from the three-marker signature and the recurrent bladder tumor pathological characteristics of 34 recurrence patients.

FUNDAMENTO: A artéria torácica interna enxertada (ATIE) patente usualmente tem fração diastólica (FD)> 50% do fluxo. O estado funcional pode ser avaliado pelo índice de reserva coronariano (IRC). OBJETIVO: Avaliar, pela ecocardiografia e pelo Doppler em nível supraclavicular, a patência e o estado funcional da ATIE. MÉTODOS: Foram coletados prospectivamente e analisados os dados de 66 pacientes submetidos a ecocardiograma sob estresse com dobutamina (EED). O grupo I (GI) ocorreu com 49 ATIE sem estenose. No grupo II (GII) (10 ATIE) havia estenose significativa (> 50% e 50%, ocorreu em 49 ATIE (GI=40, GII=8 e GIII=1) no repouso e em 61 ATIE (GI=49, GII=10 e GIII=2) durante EED. Sensibilidade, especificidade, valor preditivo positivo (VPP), valor preditivo negativo (VPN) e acurácia foram, respectivamente, em repouso, 81%, 86% ,98%, 35 % e 82%; e no EED, 100%, 71%, 97%, 100% e 97%. As ATIE com FD>50% em repouso estavam patentes e as com FD1,8, isso ocorreu em 42 ATIE (39 do GI, 2 do GII e 1 GIII), verificando-se sensibilidade = 79%; especificidade = 85,7%; VPP = 94%; VPN = 59%; e acurácia = 80,9%. O IRC no GI foi maior (p=0,02) que em GII e GIII. CONCLUSÃO: Em nosso estudo, a avaliação não-invasiva da ATIE foi efetiva para verificar patência e estado funcional. BACKGROUND: The patent internal thoracic artery graft (ITAG) usually has a diastolic fraction (DF) > 50% of the flow. The functional assessment can be evaluated by the coronary reserve index (CRI). OBJECTIVE: The objective was to evaluate the patency and functional status of the ITAG through echocardiography and Doppler. METHODS: Data from sixty-six patients who underwent dobutamine-stress echocardiography (DSE) were prospectively collected and analyzed. Group I (GI) had 49 ITAG without stenosis, Group II (GII), 10 ITAG with significant stenosis (> 50% and 50%, it was observed in 49 ITAG (GI= 40, GII= 8 and GIII= 1) at rest and in 61 ITAG (GI=49, GII=10 and GIII=2) during DSE. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were respectively, 81%, 86%, 98%, 35% and 82%, and 100%, at rest and 71%, 97%, 100% and 97% in the DSE. The ITAG with DF>50% at rest were patent and the ones with DF1.8 for a good functional status, it was observed in 42 ITAG (39 from GI, 2 from GII and 1 from GIII), determining sensitivity=79%, specificity=85.7%, PPV=94%, NPV=59% and accuracy= 80.9%. The CRI in GI was higher (p= 0.02) than in GII or GIII. CONCLUSION: In our study, the non-invasive assessment of the ITAG was effective to verify the patency and the functional status.

The patent internal thoracic artery graft (ITAG) usually has a diastolic fraction (DF)50% of the flow. The functional assessment can be evaluated by the coronary reserve index (CRI).The objective was to evaluate the patency and functional status of the ITAG through echocardiography and Doppler.Data from sixty-six patients who underwent dobutamine-stress echocardiography (DSE) were prospectively collected and analyzed. Group I (GI) had 49 ITAG without stenosis, Group II (GII), 10 ITAG with significant stenosis (50% and100%) and Group III (GIII) had 7 ITAG with total occlusion. Diameters and Doppler spectrums from the ITAG at rest and during DSE were evaluated.Considering patency a DF50%, it was observed in 49 ITAG (GI= 40, GII= 8 and GIII= 1) at rest and in 61 ITAG (GI=49, GII=10 and GIII=2) during DSE. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were respectively, 81%, 86%, 98%, 35% and 82%, and 100%, at rest and 71%, 97%, 100% and 97% in the DSE. The ITAG with DF50% at rest were patent and the ones with DF50% in the DSE presented total occlusion. Considering a CRI1.8 for a good functional status, it was observed in 42 ITAG (39 from GI, 2 from GII and 1 from GIII), determining sensitivity=79%, specificity=85.7%, PPV=94%, NPV=59% and accuracy= 80.9%. The CRI in GI was higher (p= 0.02) than in GII or GIII.In our study, the non-invasive assessment of the ITAG was effective to verify the patency and the functional status.