Michael Pešl

Narrow Band Imaging Cystoscopy Improves the Detection of Non-muscle-invasive Bladder Cancer

OBJECTIVES To determine whether narrow band imaging (NBI) improves detection of non-muscle-invasive bladder cancer over white-light imaging (WLI) cystoscopy. METHODS We conducted a prospective, within-patient comparison on 103 consecutive procedures on 95 patients scheduled for (re-) transurethral resection of a bladder tumor (84) or bladder biopsies (19) in the Academic Medical Center, Amsterdam (September 2007-July 2009) and in the General Faculty Hospital, Prague (January 2009-July 2009). WLI and NBI cystoscopy were subsequently performed by different surgeons who independently indicated all tumors and suspect areas on a bladder diagram. The lesions identified were resected/biopsied and sent for histopathological examination. Number of patients with additional tumors detected by WLI and NBI were calculated; mean number of urothelial carcinomas (UCs) per patient, detection rates, and false-positive rates of both techniques were compared. RESULTS A total of 78 patients had a confirmed UC; there were 226 tumors in total. In 28 (35.9%) of these patients, a total of 39 additional tumors (17.3%) (26pTa, 6pT1, 1pT2, 6pTis) were detected by NBI, whereas 4 additional tumors (1.8%) (1pTa, 1pT1, 2pTis) within 3 patients (2.9%) were detected by WLI. The mean (SD, range) number of UCs per patient identified by NBI was 2.1 (2.6, 0-15), vs 1.7 (2.3, 0-15) by WLI (P <.001). The detection rate of NBI was 94.7% vs 79.2% for WLI (P <.001). The false-positive rate of NBI and WLI was 31.6% and 24.5%, respectively (P <.001). CONCLUSIONS NBI cystoscopy improves the detection of primary and recurrent nonmuscle invasive bladder cancer over WLI. However, further validation of the technique with comparative studies is required.

Urinary Cytology and Quantitative BTA and UBC Tests in Surveillance of Patients with pTapT1 Bladder Urothelial Carcinoma

OBJECTIVES To compare results of urinary cytology, quantitative detection of human complement factor H-related protein (BTA TRAK), and urinary fragments of cytokeratins 8 and 18 (UBC IRMA) with the recurrence status in patients with pTapT1 bladder cancer and to define the possible role of these methods in a surveillance protocol. METHODS We collected urine from 88 consecutive patients with primary pTapT1 tumors before the first transurethral resection (TURB) and before each follow-up cystoscopy. In all samples urinary cytology and quantitative BTA and UBC tests were performed. We compared results with recurrence status and with tumor characteristics in the case of recurrence. We constructed receiver operator characteristic (ROC) curves for quantitative methods. In addition, we evaluated individual cutoffs based on pretreatment levels. RESULTS During the mean follow-up of 16.96 months, we performed 313 cystoscopies, 93 of which were positive in 51 patients. The sensitivity and specificity of cytology, BTA, and UBC were 19.8% and 99%, 53.8% and 83.9%, and 12.1% and 97.2%, respectively. The sensitivity of pTis detection was 66.6%, 0%, and 100%, respectively. With cutoffs set to a sensitivity of 90%, the specificity of BTA and UBC dropped to 24.8% and 20.4%, respectively. Individually calculated cutoffs did not provide a significant benefit. CONCLUSIONS Because of high specificity and sensitivity in pTis detection, urinary cytology fulfills requirements for an adjunctive method to cystoscopy. Quantitative BTA and UBC tests have a low sensitivity in the detection of bladder cancer recurrence and cannot be used routinely to reduce the number of cystoscopies during follow-up.

Large cell neuroendocrine carcinoma of the urinary bladder with lymphoepithelioma-like features.

The group of undifferentiated carcinomas of the urinary bladder encompasses small cell undifferentiated carcinoma, giant cell carcinoma, lymphoepithelioma-like carcinoma (LELC), and large cell neuroendocrine carcinoma (LCNEC). These tumors are either pure or can be associated with other components, such as transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. We report a case of LCNEC of the urinary bladder in a 54-year-old woman. Histologically, the tumor showed features of LELC; immunohistochemically, the tumor cells reacted to chromogranin A, NSE, and synaptophysin. In addition to these neuroendocrine markers, tumor cells were positive for cytokeratin CAM 5.2 and AE1/AE3, and there was focal positivity for vimentin. In situ hybridization for the detection of Epstein-Barr virus was negative. Despite radical cystourethrectomy and six courses of chemotherapy, the patient developed metastases invading the left inguinal lymph nodes 11 months postoperatively. Currently, 16 months postoperatively, the patient has developed metastases spreading into the lymph nodes of the right ischiorectal fossa; therefore, she is receiving a new cyclus of chemotherapy. There are only three previously reported cases of LCNEC of the urinary bladder, and the significance of neuroendocrine differentiation in non-small cell carcinomas at this location remains to be established. However, LELC appears to be a separate clinicopathological entity with sensitivity to chemotherapy and a relatively favorable prognosis. The differentiation between LELC and LCNEC with prominent inflammatory reaction could be of therapeutic relevance. However, in our case, this was possible using immunohistochemistry only.

Does the Expression of Fascin-1 and Tumor Subclassification Help to Assess the Risk of Recurrence and Progression in T1 Urothelial Urinary Bladder Carcinoma?

Introduction: To evaluate the prognostic value of T1 subclassification and fascin-1 expression in T1 human urothelial cell carcinoma of the bladder. Materials and Methods: In a prospective study with 105 consecutive patients, T1 tumors were subclassified into 2 groups according to the depth of tumor invasion. The tunica muscularis mucosae was used as a landmark. The expression of fascin-1 was examined by using an anti-fascin-1 mouse monoclonal antibody and was evaluated semiquantitatively for both intensity and distribution. The patients were followed up for 27.3 ± 13.7 months. Results: The T1 tumor subclassification was feasible in 99 patients (94%). T1a tumor was detected in 77 patients (73%), T1b tumor in 22 patients (21%). An invasive tumor was found in 5 patients (4.8%) during the restaging transurethral resection of the bladder. The risk of understaging in patients with T1b tumor was 18%. There was not a significant difference in time to the recurrence in the T1a and the T1b group. The progression-free survival rates were significantly different between both groups (p = 0.0034). No correlation was found between fascin-1 positivity and the depth of tumor invasion. Fascin-1 positivity did not correlate with recurrence or the progression-free intervals. In the multivariate analysis, only the extent of lamina propria invasion was an independent predictor of the tumor progression. The fascin positivity was not an independent prognostic factor relating to the risk of recurrence or progression. Conclusion: The finding of T1b tumor was connected with a significantly higher risk of progression and understaging. The fascin-1 expression did not correlate with the depth of tumor invasion or with the tumor recurrence or progression.

Pigmented composite paraganglioma-ganglioneuroma of the urinary bladder

We report a case of a pigmented composite paraganglioma-ganglioneuroma of the urinary bladder in a 70-year-old female. Grossly, the tumor measured 6.5 cm in diameter and had arisen from the base of the urinary bladder. Histologically, the tumor was composed of approximately equal components of paraganglioma and ganglioneuroma, which were partly separated and partly mixed, and intermingled with each other. There were foci of ample dark brown pigmentation in the cytoplasm of chromaffin paraganglioma cells. The pigment was Masson-Fontana-positive and had been bleached by hydrogen peroxide (H2O2). Electron microscopy showed large, abundant, pleomorphic electron-dense granules consistent with neuromelanin. In addition, there were numerous electron-dense neurosecretory-type granules. Neuromelanin, melanin or lipofuscin are occasionally observed in paragangliomas, although the occurrence of these pigments has never been described in a composite tumor originating from either adrenal medulla or extraadrenal paraganglia. To the best of our knowledge, our report represents the first case of pigmented composite paraganglioma-ganglioneuroma and expands the morphological spectrum of these unusual tumors.

The Prognostic Value of T1 Bladder Cancer Substaging: A Single Institution Retrospective Study

Objective: To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer. Subjects and Methods: 200 patients were treated between the years 2002 and 2009. Tumours with depth of invasion above the muscularis mucosae level were categorised as pT1a and those with depth of invasion up to or beyond the muscularis mucosae as pT1b. Results: Categorisation for pT1a and pT1b was performed in 176 of 200 patients (88%). In 10 patients a muscle-invasive tumour was found in re-transurethral resection samples. 131 (79%) of 166 analysed patients had pT1a tumour and 35 (21%) had pT1b tumour. During the follow-up, in 101 (61%) patients the tumour had recurred and in 27 (16.3%) the tumour had progressed. Of all the investigated parameters, T1 substaging (p < 0.0001), grade (p = 0.0003) and the number of bacillus Calmette-Guérin instillations (p = 0.0490) were significant in predicting progression. The only significant factor for disease-specific survival was T1 substaging in univariable (p = 0.0008) and multivariable (hazard ratio 4.407) analysis. T1 substaging (p = 0.0149) and tumour multiplicity (p = 0.0448) have a statistically significant prognostic value with respect to overall survival. Conclusions: Deep invasion of the lamina propria is a significant adverse prognostic factor for tumour progression, disease-specific survival and overall survival.

Panel of Urinary Diagnostic Markers for Non-Invasive Detection of Primary and Recurrent Urothelial Urinary Bladder Carcinoma.

Objectives: To determine the combination of urinary protein markers for noninvasive detection of primary and recurrent urothelial bladder carcinomas. Methods: Urinary concentrations of 27 biomarkers (NSE, ATT, AFABP, Resistin, Midkine, Clusterin, Uromodulin, ZAG2, HSP27, HSP 60, NCAM1/CD56, Angiogenin, Calreticulin, Chromogranin A, CEACAM1, CXCL1, IL13Ra2, Progranulin, VEGFA, CarbAnhydIX, Annexin-V, TIM4, Galectin1, Cystatin B, Synuclein G, ApoA1 and ApoA2) were assessed by enzyme-linked immunosorbent assay or by electrochemiluminiscence immunoassay. Results: During the primary diagnostics, a group of 70 patients with primary occurrence of bladder cancer and 49 healthy control subjects were compared. For this clinical situation, the most accurate combination proved to be the combination of cytology with markers Midkine and Synuclein G (sensitivity 91.8%, specificity 97.5%). During the monitoring of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared with the group of 61 patients with a history of NMIBC without current disease. For this clinical situation, the most accurate combination proved to be the combination of cytology and erythrocytes count in urine sediment with markers Midkine, ZAG2, CEACAM1, and Synuclein G (sensitivity 92.68%, specificity 90.16%). A lower accuracy of the diagnostic panel and the necessity to use more markers in the case of recurrence was connected with a different structure of patients. Conclusions: Multi-marker test can significantly improve the bladder cancer detection both during the primary diagnostics and monitoring of patients with NMIBC. This outcome should result in other, larger studies.

Diagnostic Importance of Selected Protein Serum Markers in the Primary Diagnostics of Prostate Cancer

Objective: To determine a predictive model for the primary diagnosis of prostate cancer (PC) based on a multiple serum biomarker assay. Material and Methods: Between August 2011 and February 2013, a total of 387 prostate biopsies were performed. Serum or plasma concentrations of 22 biomarkers (neopterin, IGF-1, IGFBP-2, IGFBP-3, sarcosine, endoglin, TGF-β1, periostin, sPLA2-IIa, chromogranin A, ZAG2, clusterin, PSP94, PSP94bp, leptin, cathepsin D, hepsin, KLK11, PSMA, AMACR, CRISP3 and A1AT) were determined. Biomarker levels were correlated with the prostate biopsy results. Several statistical models for PC detection were created. Results: A total of 167 of the 373 evaluated patients (44.8%) were diagnosed with PC. None of the tested biomarkers reached statistical significance using the univariate analysis. However, the level of serum clusterin was not associated with any other tested parameter. Several basic models showed a higher positive predictive value than individual parameters. Addition of serum clusterin to the base model with prostate-specific antigen, digital rectal exam and prostate size significantly improved the area under curve value (0.723 vs. 0.716). Conclusion: Our findings suggested that multiple serum assays based on some promising markers may only have a limited practical benefit for the prediction of PC in the prostate biopsy.

Impact of transurethral resection with narrow band imaging on prognosis of patients with bladder carcinoma

A total of 52 consecutive subjects with multiple recurrent bladder cancer were enrolled in the retrospective study. TUR with white light (WLC) was used in 25 patients and NBI in 27 patients. The mean age of the patient population was 72 years, the mean follow-up was 7,5 months. Selected tumour risk factors (stage and grade) were evaluated (6x T1, 33x Ta, 2x CIS, 10x HG, 39x LG and 3x PUNLMP) . The tissue samples were taken by means of transurethral resection (TUR-BT), all the tumours were histologicaly verified. The disease free survival functions were compared by the means of Log-Rank test and Wilcoxon generalised test. The Kaplan-Meier method of the survival function estimation was used. Statistical analysis was performed using the SPSS 13.0 software. The level of significance was set at p=0,05. IMPACT OF TRANSURETHRAL RESECTION WITH NARROW BAND IMAGING ON PROGNOSIS OF PATIENTS WITH BLADDER CARCINOMA M.Pešl1, V.Soukup1, O.Čapoun1, Z.Vaĺová1, P.Dundr2, L.Bauerová2, T.Hanuš1 1 Dpt. of Urology, 1st School of Medicine, Charles University, Prague, The Czech Republic 2 Dtp. of Pathology, 1st School of Medicine, Charles University, Prague, The Czech Republic