Brain Response Induced by Peroneal Electrical Transcutaneous Neuromodulation Invented for Overactive Bladder Treatment, as Detected by Functional Magnetic Resonance Imaging.

OBJECTIVES: In this study, we aimed to investigate whether peroneal electrical Transcutaneous Neuromodulation invented for overactive bladder (OAB) treatment elicits activation in brain regions involved in neural regulation of the lower urinary tract. MATERIALS AND METHODS: Among 22 enrolled healthy female volunteers, 13 were eligible for the final analysis. Functional magnetic resonance imaging (fMRI) (Siemens VIDA 3T; Erlangen, Germany) was used to compare the brain region activation elicited by peroneal electrical Transcutaneous Neuromodulation with the activation elicited by sham stimulation. Each subject underwent brain fMRI recording during eight 30-second periods of rest, alternating with 30-second periods of passive feet movement using the sham device, mimicking the motor response to peroneal nerve stimulation. Subsequently, fMRI recording was performed during the analogic "off-on" stimulation paradigm using peroneal electrical transcutaneous neuromodulation. Magnetic resonance imaging data acquired during both paradigms were compared using individual and group statistics. RESULTS: During both peroneal electrical Transcutaneous Neuromodulation and sham feet movements, we observed activation of the primary motor cortex and supplementary motor area, corresponding to the cortical projection of lower limb movement. During peroneal electrical Transcutaneous Neuromodulation, we observed significant activations in the brain stem, cerebellum, cingulate gyrus, putamen, operculum, and anterior insula, which were not observed during the sham feet movement. CONCLUSIONS: Our study provides evidence that peroneal electrical Transcutaneous Neuromodulation elicits activation of brain structures that have been previously implicated in the perception of bladder fullness and that play a role in the ability to cope with urinary urgency. Our data suggest that neuromodulation at the level of supraspinal control of the lower urinary tract may contribute to the treatment effect of peroneal electrical Transcutaneous Neuromodulation in patients with OAB.

Acquired haemophilia as a complicating factor in treatment of non-muscle invasive bladder cancer: A case report.

BACKGROUND: Acquired haemophilia (AH) is a serious autoimmune haematological disease caused by the production of auto-antibodies against coagulation factor VIII. In some patients, AH is associated with a concomitant malignancy. In case of surgical intervention, AH poses a high risk of life-threatening bleeding. CASE SUMMARY: A 60-year-old female patient with multiple recurrences of non-muscle invasive bladder cancer underwent transurethral tumour resection. A severe haematuria developed postoperatively warranting two endoscopic revisions; however, no clear source of bleeding was identified in the bladder. Subsequent haematological examination established a diagnosis of AH. Treatment with factor VIII inhibitor bypass activity and immunosuppressive therapy was initiated immediately. The patient responded well to the therapy and was discharged from the hospital 21 d after the primary surgery. At the 38-mo follow-up, both AH and bladder cancer remained in complete remission. CONCLUSION: AH is a rare, life-threatening haematological disease. AH should be considered in patients with persistent severe haematuria or other bleeding symptoms, especially if combined with isolated activated partial thromboplastin time prolongation.

Is high accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) sufficient for its implementation in the urological practice?

AIMS: Currently, the only method used to differentiate between MIBC and NMIBC is transurethral resection of the bladder tumour (TURBT). Magnetic resonance and Vesical Imaging-Reporting and Data System (VI-RADS) would allow for discrimination between NMIBC and MIBC. We evaluate the sensitivity and specificity of VI-RADS in the diagnosis of muscle-invasive bladder cancer and discuss its value in everyday urological practice. METHODS: 64 patients with bladder cancer (BC) were enrolled into this prospective study. Multiparametric magnetic resonance imaging (mpMRI) was performed before transurethral resection of the bladder tumour (TURBT) and evaluated using the VI-RADS score. Score were compared to histopathology results. We evaluated the sensitivity, specificity, positive and negative predictive value of this system using both cut-off VI-RADS ≥ 3 and ≥ 4. RESULTS: Sensitivity of 92.3% (95%CI: 64.0; 99.8), specificity of 81.4% (95%CI: 69.1; 90.3), positive predictive value of 52.2% (95%CI: 30.6; 73.2) and negative predictive value of 98.0% (95%CI: 89.1; 99.9) was determined using cut off VI-RADS ≥ 3, while sensitivity of 76.9% (95%CI: 46.2; 95.0), specificity of 91.5% (95%CI: 81.3; 97.2), positive predictive value of 66.7% (95%CI: 38.4; 88.2), and negative predictive value of 94.7% (95%CI: 85.4; 98.9) was determined using cut-off VI-RADS ≥ 4. Based on our results, we consider the optimal cut-off point to be VI-RADS ≥ 3 with the overall prediction accuracy of 83.3% (95%CI: 72.7; 91.1). CONCLUSIONS: We acknowledge that mpMRI provides valuable information with regard to BC staging, however, despite its high overall accuracy, we do not consider the VI-RADS could replace TURBT in discrimination between non-muscle invasive and MIBC.

Peroneal electrical transcutaneous neuromodulation in the home treatment of the refractory overactive bladder.

INTRODUCTION AND HYPOTHESIS: The aim of this prospective, open-label, multicenter, noncomparative study was to evaluate the efficacy and safety of peroneal electrical transcutaneous neuromodulation (peroneal eTNM®) using the URIS® neuromodulation system as a home treatment for refractory overactive bladder (OAB). METHODS: The patients were treated with daily peroneal eTNM® for 30 min over a 6-week period. The primary endpoint was defined as the proportion of responders, i.e., participants with ≥ 50% reduction in the average daily sum of severe urgency episodes (defined as "I could not postpone voiding but had to rush to the toilet in order not to wet myself") and urgency incontinence episodes. In addition, bladder diary variables, symptom severity (OAB V8 questionnaire), treatment satisfaction (visual analog scale), and pain perception (visual analog scale) were evaluated at baseline (BL), at week 4 (W4), and at the end of treatment (EoT). Safety evaluations included monitoring of the incidence and severity of adverse events (AEs). Changes in time were analyzed using the nonparametric one-way ANOVA Friedman test for categorical variables and the Wilcoxon rank-sum test for the noncategorical variables. RESULTS: In total, 40 subjects were screened and 29 were included in the full analysis set. The proportion of responders was 86% at W4 and 79% at EoT. There was a significant reduction in frequency (p<0.001), number of severe urgency episodes (p< 0.001), number of urgency incontinence episodes (p=0.001), and number of nocturia episodes (p=0.002). There was a significant improvement in the OAB V8 score and treatment satisfaction (both p<0.001). Two mild treatment-related AEs were recorded. Both patients recovered without sequelae and completed the study. CONCLUSIONS: Peroneal eTNM® proved to be a highly effective and safe method for the home treatment of OAB, providing a therapeutic response in approximately 80% of patients.

Peroneal Electrical Transcutaneous NeuroModulation as a New Treatment for Patients with Overactive Bladder: An Initial Clinical Experience.

INTRODUCTION: The aim of this study was to determine whether peroneal electrical Transcutaneous NeuroModulation (peroneal eTNM®) using the URIS® neuromodulation system can be used in individuals with refractory overactive bladder (OAB). METHODS: Eighteen female patients with idiopathic OAB who failed previous behavioral and pharmacological therapy were enrolled. Patients were treated with the URIS® neuromodulation system using active electrodes placed on the popliteal fossa, targeting the peroneal nerve for 30 min once a week for 12 weeks. Changes in OAB symptoms and patient-reported outcomes from baseline to the end of the study were analyzed. A nonparametric Wilcoxon signed-rank test was used to assess changes in variables. Statistical significance was defined as p ≤ 0.05. RESULTS: We observed a significant reduction in micturition frequency (p = 0.022), number of severe urgency episodes (p < 0.001), urgency incontinence episodes (p = 0.001), and nocturia episodes (p = 0.027). A decrease in Patient Perception of Bladder Condition score (p < 0.001) was also observed. Posttreatment, 15 patients (83.3%) reported a moderate or significant reduction in their bladder bother. Throughout the study, two adverse events were recorded with no causal relationship to the study treatment. DISCUSSION/CONCLUSIONS: Our study documented a significant reduction in all OAB symptoms and an improvement in all patient-reported outcomes in patients treated with peroneal eTNM® using the URIS® neuromodulation system.

Advanced Reconstruction of Vesicourethral Support (ARVUS) during Robot-assisted Radical Prostatectomy: One-year Functional Outcomes in a Two-group Randomised Controlled Trial.

BACKGROUND: The advent of robotics has facilitated new surgical techniques for radical prostatectomy. These allow adjustment of pelvic anatomical and functional relationships after removal of the prostate to ameliorate postprostatectomy incontinence (PPI) and reduce the time to complete continence. OBJECTIVES: To describe the results of a new surgical technique for reconstruction of vesicourethral anastomosis using the levator ani muscle for support during robot-assisted radical prostatectomy (RARP). DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomised, single-blind study among 66 consecutive patients with localised prostate cancer (cT1-2N0M0) undergoing RARP from June to September 2014, 32 using the new technique and 34 using the standard posterior reconstruction according to Rocco. SURGICAL PROCEDURE: In the advanced reconstruction of vesicourethral support (ARVUS) intervention group, the fibres of the levator ani muscle, Denonvilliers fascia, retrotrigonal layer, and median dorsal raphe were used to form the dorsal support for the urethrovesical anastomosis. Suture of the arcus tendineus to the bladder neck served as the anterior fixation. MEASUREMENTS: We compared demographic data and preoperative and postoperative functional and oncologic results for the two groups. The primary endpoint was continence evaluated at different time points (24h, 2, 4, and 8 wk, and 6 and 12 mo). The secondary endpoints were perioperative and postoperative complications and erectile function. RESULTS AND LIMITATIONS: Using a continence definition of 0 pads/d, the continence rates for the ARVUS versus the control group were 21.9% versus 5.9% at 24h (p=0.079), 43.8% versus 11.8% at 2 wk (p=0.005), 62.5% versus 14.7% at 4 wk (p<0.001), 68.8% versus 20.6% at 8 wk (p<0.001), 75.0% versus 44.1% at 6 mo (p=0.013), and 86.66% versus 61.29% at 12 mo (p=0.04). International Index of Erectile Function questionnaire results at 6 and 12 mo after surgery showed similar potency rates for the control group (40.0% and 73.33%) and the ARVUS group (38.8% and 72.22%). There were four postoperative complications (2 in each group): three haematomas requiring transfusion and one lymphocele that needed drainage. No urinary retention, anastomosis leak, or perineal pain was observed. Limitations include the small sample size and the single-institution design. CONCLUSIONS: The ARVUS technique yielded better urinary continence results than standard posterior reconstruction, with no negative impact on erectile function, complication rate, or oncologic outcome. External validation is warranted before clear recommendations can be made. PATIENT SUMMARY: We showed that postprostatectomy incontinence can be assuaged using a new technique for vesicourethral anastomosis reconstruction during robot-assisted radical prostatectomy (RARP). This could significantly improve the quality of life of patients after RARP. More studies are needed to support our results.

Outcomes of adrenalectomy in patients with primary hyperaldosteronism--a single centre experience.

INTRODUCTION: Primary hyperaldosteronism is a common cause of secondary hypertension. In patients with proven unilateral overproduction of aldosterone adrenalectomy can cure hyperaldosteronism with high probability and a positive effect on hypertension. The aim of the study was to determine the effects of unilateral adrenalectomy on blood pressure and laboratory parameters. The secondary objective was to identify parameters that would allow the prediction of hypertension cure. METHODS: We performed a cross-sectional analysis of the data of patients who underwent unilateral adrenalectomy for primary aldosteronism at the Department of Urology of University Hospital Olomouc in the years 2000-2011. We assesed the preoperative clinical conditions of patients, the results of biochemical and radiological examinations, course of the surgery and post-operative course including laboratory and clinical parameters during the 12 months postoperatively. RESULTS: 62 patients underwent adrenalectomy for primary aldosteronism in this period. Four patients were excluded from the study due to surprising histology (myelolipoma in 2, carcinoma in 2), seven patients had incomplete postoperative data. The statistical analysis therefore included 51 patients, of which 57% were females. CT or MRI was performed in all patients; 63% patients underwent superselective catheterization of adrenal veins (AVS). Adrenalectomy was performed in all cases laparoscopically. Histology most often showed adrenal hyperplasia (59%), adenoma was detected in 37% and adenoma on the basis of micronodular hyperplasia in 4%. Twelve months after surgery the antihypertensive drugs were discontinued in 17/51 (33%) and the number or dose of antihypertensive drugs was reduced in 25/51 (49%). Normokalemia and normalisation of the aldosterone-renin ratio (ARR) was detected in 92% and 84% of the patients. Performing AVS did not statistically significantly influence the rate of blood pressure control or normalization of ARR, which is probably due to small study size. This study demonstrated a better effect of surgery on blood pressure in younger patients. CONCLUSIONS: Unilateral adrenalectomy had a positive effect in 82% of the patients operated for primary aldosteronism and lead to either blood pressure normalization or reduction of the antihypertensive medication.

When less is more: a simple predictive model for repeated prostate biopsy outcomes.

OBJECTIVES: To present a new predictive model for repeated prostate biopsy outcomes. Several practical problems are described that arise when searching for a proper model among those that already exist. A new model is developed with only two explanatory variables and a simple graphical output. METHODS: This is a retrospective cohort study based on data collected from December 2006 to June 2011 at the Clinic of Urology of the University Hospital in Olomouc, Czech Republic. The cohort consists of 221 patients who underwent the first repeated biopsy after an initial biopsy with a negative outcome. All patients had prostate-specific antigen (PSA) levels between 1.5 and 16.5 ng/mL and a prostate volume not greater than 100mL. A logistic regression model was fitted. RESULTS: Of the 221 patients, 29 (13%) were diagnosed with prostate cancer on the repeated biopsy. The final model includes the PSA level and the transitory zone volume as predictors. Its accuracy is 76.4%. The cut-off point of 0.0687 in the predicted positive repeated biopsy outcome assures 95% sensitivity and prevents 42% of unnecessary biopsies. CONCLUSIONS: The accuracy of the model is comparable to that of more complex models (with more than two predictors) published in the literature. The model includes only two routinely measured variables, and hence it is accessible for a wide range of practitioners. The simple graphical outcome makes the model even more attractive.

Automatic cell cloning assay for determining the clonogenic capacity of cancer and cancer stem-like cells.

The clonogenic assay is a well-established in vitro method for testing the survival and proliferative capability of cells. It can be used to determine the cytotoxic effects of various treatments including chemotherapeutics and ionizing radiation. However, this approach can also characterize cells with different phenotypes and biological properties, such as stem cells or cancer stem cells. In this study, we implemented a faster and more precise method for assessing the cloning efficiency of cancer stem-like cells that were characterized and separated using a high-speed cell sorter. Cell plating onto a microplate using an automatic cell deposition unit was performed in a single-cell or dilution rank mode by the fluorescence-activated cell sorting method. We tested the new automatic cell-cloning assay (ACCA) on selected cancer cell lines and compared it with the manual approach. The obtained results were also compared with the results of the limiting dilution assay for different cell lines. We applied the ACCA to analyze the cloning capacity of different subpopulations of prostate and colon cancer cells based on the expression of the characteristic markers of stem (CD44 and CD133) and cancer stem cells (TROP-2, CD49f, and CD44). Our results revealed that the novel ACCA is a straightforward approach for determining the clonogenic capacity of cancer stem-like cells identified in both cell lines and patient samples.

Genetic determinants of prostate cancer: a review.

BACKGROUND: In prostate cancer, early detection and appropriate treatment remain key approaches. But given the constantly increasing incidence, prostate cancer ethiopathogenetic determinants are a current focus of attention. Although the development of this cancer is influenced by both environmental and genetic factors which are as yet ill-defined, genetic studies have revealed gene abnormalities which may be specifically associated with the risk of prostate cancer: changes in genes for the androgen receptor, RNAseL, ELAC2, MSR1, BRCA 1 and 2, HPCX, KLF6, HPC20 and fusion genes, e.g. TMPRSS2-ERG). Despite differing research results from molecular biological studies, these techniques can assist in earlier diagnosis enabling timely initiation of treatment. METHODS: Methods and literature: MEDLINE search was performed to collect both original and review articles addressing prostate cancer and genetic risk factors using key words genetics, prostate cancer and risk. CONCLUSIONS: A number of potential genetic risk factors/markers has been identified which may in near future contribute to earlier diagnosis of prostate cancer so that earlier treatment can be started. Despite many promising data we have found differing results and therefore we suppose further research should be conducted to achieve more precise conclusion. This review focuses on current knowledge of the genetic factors affecting the development of prostate cancer.

Prostate cancer detection yield in repeated biopsy is independent of the diagnosis of earlier biopsies.

BACKGROUND: We analyzed data gathered from initial and repeated prostate biopsies at the University Hospital in Olomouc, Czech Republic. We evaluated the diagnostic yield of repeated transrectal ultrasound (TRUS) guided biopsies. We also assessed whether the result of the repeated biopsy depended on the benign diagnosis of the previous biopsy. METHODS: From June 2006 till December 2008, the total of 794 men underwent a TRUS guided biopsy. The following parameters were recorded for each patient: age, total Prostatic Specific Antigen (PSA) level, free PSA level, digital rectal examination record, total prostate volume, and the histo-pathological evaluation. For patients undergoing a repeated biopsy, the histo-pathological result of the previous biopsy was also available, as well as the total number of previous biopsies and the time since the last biopsy. These data were analyzed using standard statistical methods. RESULTS: Initial biopsy was positive for prostate cancer in 157 out of 566 men (27.7%). The total PSA level was confirmed to be a significant (P < 0.001) predictor of prostate cancer. The ratio of free PSA to total PSA (the so-called PSA index) was found to be significantly lower (P < 0.001) for patients suffering from adenocarcinoma. A total of 191 men underwent a repeated biopsy. The repeated biopsy was positive for adenocarcinoma in 39 cases (20.4%). Although this yield is lower, the significance is at the threshold (P = 0.04700). In the group of re-biopted men, total PSA level and PSA index were again significant (P = 0.0024 and P = 0.0015 respectively) predictive factors for prostate carcinoma. The diagnostic yield of repeated biopsy was assessed with respect to the most common types of the benign findings in the previous biopsy--adenomyomatous hyperplasia, inflammation, high grade prostatic intraepithelial neoplasia, and suspected adenocarcinoma. No significant difference in the diagnostic yield was found (P = 0.38431). CONCLUSIONS: Total PSA level and PSA index are the most significant precursors of adenocarcinoma in both initial and repeated biopsy. The histo-pathological result of a repeated biopsy was found to be independent of the type of benign diagnosis of the previous biopsy. A substantial number of prostate cancer is diagnosed in repeated biopsies which advocates for the indication of a repeated biopsy in case of a negative result of the initial one.

The F1-F2 vowel chart for Czech whispered vowels a, e, i, o, u.

AIM: The aim of this contribution is to present the formant chart of the Czech vowels a, e, i, o, u and show that this can be achieved by means of digital methods of sound processing. METHOD: A group of 35 Czech students of the Pedagogical Faculty of Palacky University was tested and a record of whispered vowels was taken from each of them. The record was digitalized and processed by the Discrete Fourier Trasform. The result is the power spectrum of the individual vocals - the graphic output consists of a plot of the relative power of individual frequencies in the original sound. The values of the first two maxima which represent the first and the second formants were determined from the graph. The values were plotted on a formant chart. RESULTS: Altogether, 175 spectral analyses of individual vowels were performed. In the resulting power spectrum, the first and the second formant frequencies were identified. The first formant was plotted against the second one and pure vocal formant regions were identified. CONCLUSION: Frequency bands for the Czech vowel "a" were circumscribed between 850 and 1150 Hz for first formant (F1) and between 1200 and 2000 Hz for second formant (F2). Similarly, borders of frequency band for vowel "e" they were 700 and 950 Hz for F1 and 1700 and 3000 Hz for F2. For vowel "i" 300 and 450 Hz for F1 and 2000 and 3600 Hz for F2, for vowel "o" 600 and 800 Hz for F1 and 600 and 1400 Hz for F2, for vowel "u" 100 and 400 Hz for F1 and 400 and 1200 Hz for F2. DISCUSSION: At low frequencies it is feasible to invoke the source-filter model of voice production and associate vowel identity with frequencies of the first two formants in the voice spectrum. On the other hand, subject to intonation, singing or other forms of exposed voice (such as emotional speech, focused speech), the formant regions tend to spread. In spectral analysis other frequencies dominate, so specific formant frequency bands are not easily recognizable. Although the resulting formant map is not much different from the formant map of Peterson, it carries basic information about specific Czech vowels. The results may be used in further research and in education.

In reference to phonation larynx fixation: computer graphic record.

The vocal apparatus serves phonation. It represents a biocybernetic self-regulating system, disposing of a feedback network of the central nervous system. The larynx is a self-induced vibrating system. The larynx, functioning as the phonation apparatus of the vocal apparatus, is a source of human voice. In every individual its frequency range corresponds to about eight semitones in speech and about two octaves of the so-called chest register in singing, denoted also as a thoracic or modal voice. This is followed by one more octave of the so-called cranial register or falsetto voice. We were interested in changes of the larynx positions at intonation in the fundamental singing registers, both modal and falsetto, in professional male singers. At our disposal were 11 professional male singers. We investigated changes in the position of the laryngeal structures simultaneously with the aid of an X-ray apparatus, the acoustic and mechanical signals registered by means of the B & K 4369 acceleration recorder. It has been found that at phonation with the modal voice a change in the position of the laryngeal structures takes place in two different ways, whereas the larynx movements at falsetto remain the same. It has been suggested that a complex fixation apparatus participates in the phonation larynx movements. Of the same complex character are also the problems connected with the examination of the entire vocal apparatus. For the purpose of compiling the present pieces of knowledge in the field of human voice studies, we have made the most advantageous use of the presently most complex system Authorware for the production of some interactive multimedial programmes on personal computers.