T. Hanus

Surgical treatment of stress incontinence in men.

The committee was charged with the responsibility of reviewing and evaluating all published data relating to surgical treatment of male urinary incontinence since the previous consultation in 2004.

Female urethra- sparing cystectomy and orthotopic bladder replacement

OBJECTIVE Orthotopic bladder replacement after cystoprostatectomy has long become the method of choice in the treatment of infiltrating bladder cancer in males. Very good quality of life in patients thus treated stimulated the work on a similar approach applicable to females. METHODS Twelve females were treated by urethra-sparing cystectomy. The surgical technique preserves not just the urethra itself but also the pelvic floor and relevant innervation. RESULTS Diurnal continence was achieved in 11 patients, 1 of whom had a so-called hypercontinence with a residual volume of 300 ml. The remaining patient suffered from stress incontinence. CONCLUSION The described urethra-sparing radical cystectomy in female patients with a urothelial tumor, with normal pelvic floor and with a low risk of secondary affection of the urethra, permits reconstructing a continent orthotopic neobladder from a detubularized intestinal segment.

The expression of PAX5, p53 immunohistochemistry and p53 mutation analysis in superficial bladder carcinoma tissue. Correlation with pathological findings and clinical outcome.

Objectives: The expression pattern of PAX5 in thetissue of superficial bladder transitional cell carcinoma (TCC), itsprognostic value and its correlation with p53immunohistochemistry and p53 mutation analysis were evaluated.Methods: Study comprised 61 patients with histologicallyconfirmed superficial bladder TCC. Expression level of PAX5mRNA was investigated using reverse transcriptase-polymerase chainreaction (RT-PCR) and determined semiquantitatively. The presence ofp53 mutations was determined by SSCP and confirmed by directsequencing. The p53 immunohistochemistry was performed with DO1antibody and semiquantitatively evaluated using HSCORE (HS) method. Asthe control group for the evaluation of the PAX5 expressionserved 8 men with benign prostatic hyperplasia. Results:PAX5 expression was found in 50 patients with bladder TCC butin no patient from the control group. Its quantity however correlatedneither with the stage nor with the grade of the tumor. P53mutation was confirmed only in 1 patient with pTaG2 tumor in exon 5(deletion of proline 128). On the contrary, positive immunohistochemicalstaining of p53 was detected in most patients. Using the cutoffvalue of HS 200, 56.9% of patients showed p53overexpression. Quantity of p53 immunochistochemical positivitydid not correlate with the quantity of PAX5 expression. Usingthe cutoff values of HS 200 for p53 and of 0.2 forPAX5, 7 of 8 patients with future progression had p53and 4 had PAX5 overexpression respectively.Conclusion: The expression of gene PAX5 is a frequentevent in superficial TCC of the bladder.

The European Association of Urology (EAU) Guidelines Methodology: A Critical Evaluation

OBJECTIVES Guidelines can be produced and written in numerous ways. The aim of the present article is to describe and evaluate the method currently used to produce the European Association of Urology (EAU) guidelines. DESIGN, SETTING, AND PARTICIPANTS The methodology is described in detail, compared to other urologic guidelines by members of the EAU Guidelines Office Board. MEASUREMENTS The new methodology is evaluated by the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. RESULTS AND LIMITATIONS The currently used methodology is adapted to the aims and objectives as established by the EAU for their guidelines; wide coverage (essentially all fields of urology) and useful to urologists all over Europe. The frequent updates are easily accessible in a printed and electronic format. The AGREE instrument supports these strong points, but also identifies potentially weak points, such as no patient involvement, no formal validation of the guidelines texts prior to publication, and lack of discussion of organisational barriers and cost implications. CONCLUSION The currently used methodology for the production of EAU guidelines fulfils the associations main objectives related to their guidelines, but the texts will benefit from the inclusion of country-specific cost and organisational data. For the practising clinician, these guidelines will help to take science into clinical practice.

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.

Causes and Treatment of Residual Urine Volume after Orthotopic Bladder Replacement in Women

Objectives: Intact innervation of the female urethra is conditional for normal urination. In the past, urethrectomy was performed as part of cystectomy. After intense anatomical studies of the female pelvis, urethral–function–sparing cystectomy was developed.Methods: Our clinical group consists of 41 female patients who were operated from 1993 to 1998 for bladder cancer, utilizing cystectomy with orthotopic bladder replacement.Results: In 28 patients, complete daytime continence was restored and in 13 patients, daytime continence was socially satisfactory (1–2 pads were used due to mild stress incontinence). The drawback of orthotopic replacements in females is the frequent development of serious residual volume, which was seen in onethird of the 41 patients. The functional results of orthotopic neobladders and therapy of residual urine volume were documented using urodynamic studies.Conclusions: Postvoiding residual volume may be caused by isolated dysfunction of the urethra and can be treated with clean intermittent self–catheterization or with α–blockers, which improve evacuation of the neobladder.

Persistence in the treatment of overactive bladder syndrome (OAB) with mirabegron in a multicenter clinical study

OBJECTIVE The objective of this project was to evaluate treatment persistence in patients being treated for overactive bladder syndrome (OAB) with mirabegron, employing clinical follow-up in a prospective, multicenter study. STUDY DESIGN This is an analysis of patients who started treatment with mirabegron between May and September 2014 and were evaluated 1year after treatment commenced. During this evaluation we determined how many patients stopped treatment and established their reasons for discontinuation. RESULTS 206 patients being treated for OAB with mirabegron were evaluated a year after starting treatment. It emerged that 60 patients (29.1%) had discontinued the treatment, citing the following reasons: 24/60 insufficient treatment efficacy, 26/60 other reasons, while 10 members of the group discontinued treatment because of side effects. 75 out of 206 patients were ≤60 years old and 28% terminated the study prematurely: 131 out of 206 were >60years old and 29.2% terminated the study prematurely. In the group of patients without previous OAB treatment 35.7% discontinued treatment with mirabegron, while 28.1% of patients with previous anticholinergic treatment discontinued treatment. CONCLUSION In our clinical prospective multicenter study, persistence in treatment with mirabegron reached a figure of 71%.

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.

Urinary Cell-Free DNA Quantification as Non-Invasive Biomarker in Patients with Bladder Cancer

Introduction: Concentration of urinary cell-free DNA (ucfDNA) belongs to potential bladder cancer markers, but the reported results are inconsistent due to the use of various non-standardised methodologies. The aim of the study was to standardise the methodology for ucfDNA quantification as a potential non-invasive tumour biomarker. Material and Methods: In total, 66 patients and 34 controls were enrolled into the study. Volumes of each urine portion (V) were recorded and ucfDNA concentrations (c) were measured using real-time PCR. Total amounts (TA) of ucfDNA were calculated and compared between patients and controls. Diagnostic accuracy of the TA of ucfDNA was determined. Results: The calculation of TA of ucfDNA in the second urine portion was the most appropriate approach to ucfDNA quantification, as there was logarithmic dependence between the volume and the concentration of a urine portion (p = 0.0001). Using this methodology, we were able to discriminate between bladder cancer patients and subjects without bladder tumours (p = 0.0002) with area under the ROC curve of 0.725. Positive and negative predictive value of the test was 90 and 45%, respectively. Conclusion: Quantification of ucf DNA according to our modified method could provide a potential non-invasive biomarker for diagnosis of patients with bladder cancer.