Preliminary outcomes of the European multicentre experience with the ZSI 375 artificial urinary sphincter for treatment of stress urinary incontinence in men.

INTRODUCTION: The ZSI 375 is a new artificial urinary sphincter utilised in men suffering from stress urinary incontinence (SUI). We present the first European multicentre study on the effectiveness of ZSI 375. MATERIAL AND METHODS: This study was conducted in a retrospective, non-randomized format in centres across Europe. Between May 2009 and December 2014, ZSI 375 was fitted in 109 SUI patients following radical prostatectomy, transurethral resection of prostate (TURP), rectal surgery and high intensity focused ultrasound (HIFU). Patients with history of pelvic radiotherapy or previous surgical treatment for incontinence or stricture were excluded from the series. Follow-up was completed by December 2016. The key outcome measures included overall improvement and complication rates. RESULTS: A total of 109 patients in 10 European centres were recruited and had the ZSI 375 device implanted. The average patient age was 72 years old. The indication for the majority of patients was incontinence following radical prostatectomy (100/109 patients, 91.74%). On average, patients were incontinent for 48.6 months prior to treatment. All patients used ≥4 pads daily at baseline and thus were classified as suffering from 'severe incontinence'. The average follow-up until the final visit was 43 months. The pad usage decreased to 0.84 on average by the last visit. There were no reported cases of device infection. A total of 9 patients had urethral cuff erosion (8.25%),which was the most common complication in this series. A further 3 men (2.75%) experienced mechanical failure requiring subsequent device reimplantation. The implantation of the ZSI 375 device was considered successful in 92.66% of patients. CONCLUSIONS: The ZSI 375 is an effective surgical treatment option in men with severe stress urinary incontinence.

Heterogeneity in the nonplanarity and arterial curvature of arteriovenous fistulas in vivo.

OBJECTIVE: Native arteriovenous fistulas (AVFs) for hemodialysis are susceptible to nonmaturation. Adverse features of local blood flow have been implicated in the formation of perianastomotic neointimal hyperplasia that may underpin nonmaturation. Whereas computational fluid dynamic simulations of idealized models highlight the importance of geometry on fluid and vessel wall interactions, little is known in vivo about AVF geometry and its role in adverse clinical outcomes. This study set out to examine the three-dimensional geometry of native AVFs and the geometric correlates of AVF failure. METHODS: As part of an observational study between 2013 and 2016, patients underwent creation of an upper limb AVF according to current surgical best practice. Phase-contrast magnetic resonance imaging was performed on the day of surgery to obtain luminal geometry along with ultrasound measurements of flow. Magnetic resonance imaging data sets were segmented and reconstructed for quantitative and qualitative analysis of local geometry. Clinical maturation was evaluated at 6 weeks. RESULTS: There were 60 patients who were successfully imaged on the day of surgery. Radiocephalic (n = 17), brachiocephalic (n = 40), and brachiobasilic (n = 3) fistulas were included in the study. Centerlines extracted from segmented vessel lumen exhibited significant heterogeneity in arterial nonplanarity and curvature. Furthermore, these features are more marked in brachiocephalic than in radiocephalic fistulas. Across the cohort, the projected bifurcation angle was 73 ± 16 degrees (mean ± standard deviation). Geometry was preserved at 2 weeks in 20 patients who underwent repeated imaging. A greater degree of arterial nonplanarity (log odds ratio [logOR], 0.95 per 0.1/vessel diameter; 95% confidence interval [CI], 0.22-1.90; P = .03) and a larger bifurcation angle (logOR, 0.05 per degree; 95% CI, 0.01-0.09; P = .02) are associated with a greater rate of maturation, as is fistula location (upper vs lower arm; logOR, -1.9; 95% CI, -3.2 to 0.7; P = .002). CONCLUSIONS: There is significant heterogeneity in the three-dimensional geometry of AVFs, in particular, arterial nonplanarity and curvature. In this largest cohort of AVF geometry to date, the effect of individual geometric correlates on maturation is uncertain but supports the premise that future modeling studies will need to acknowledge the complex geometry of AVFs.

Archetype and Rearranged Non-coding Control Regions in Urothelial Bladder Carcinoma of Immunocompetent Individuals.

BACKGROUND: Polyomaviruses (PyVs) are potential transforming viruses. Despite their involvement in human tumours still being debated, there is evidence to suggest a role for PyVs in bladder carcinoma (BC). Therefore, a possible association between PyVs and BC was investigated. MATERIALS AND METHODS: Urine, blood and fresh bladder tissue specimens were collected from 29 patients with BC. PyV prevalence, non-coding control region (NCCR) organization and genotypic analysis were assessed. RESULTS: Data showed a significant prevalence of John Cunningham (JC) PyV in BC tissues and in urine with respect to BKPyV, while simian virus 40 was not revealed. A BKPyV rearranged NCCR sequence was isolated, whereas a JCPyV archetypal structure was consistently retained. A prevalence of European genotypes was observed. CONCLUSION: Our data would suggest a JCPyV involvement in cancer progression and a BKPyV association with BC pathogenesis in immunocompetent patients. However, further work is necessary to better understand the exact role of PyVs in urothelial carcinogenesis.

Dendritic cells in blood and urine samples from bladder cancer patients undergoing BCG immunotherapy.

OBJECTIVES: Immunotherapy with BCG (Bacille Calmette-Guérin) after transurethral resection of the bladder tumor represents a highly effective primary treatment for intermediate and high-risk superficial bladder cancer. The effectiveness of this therapy has been documented, but its mechanism of action is not clear yet. In the present study, we investigated the changes of dendritic cells (DC) numbers in peripheral blood and urine of patients with superficial bladder cancer undergoing BCG intravescical therapy. MATERIAL AND METHOD: We have enumerated plasmacytoid and myeloid DCs in the peripheral blood and in the urine of patients with bladder cancer in order to clarify the role of these cells in the evolution of the disease and the effect of therapy. DCs in blood and urine samples were assessed using the single-platform TruCOUNT assay with monoclonal antibodies. The study population included 37 healthy donors and 13 patients with diagnosis of primitive superficial bladder cancer. RESULTS: At the time of diagnosis a reduction of blood DCs was found in patients as opposed to healthy donors, while DCs were not found in the urine in the same way as in healthy subjects. Six of these patients were followed before and after weekly and monthly instillations of BCG. In the peripheral blood, we observed an immunological recovery of DCs from the third weekly instillation up to the sixth. In the urine of patients, we didn't find mDCs or pDCs at T0, but we found a statistically significant change from the third instillation up to the sixth. On the contrary, we didn't find mDCs in urine during monthly instillation. CONCLUSIONS: DC Count could be used in the monitoring of patients undergoing BCG therapy. Immunological restoration of mDC numbers in peripheral blood and the efflux in urine could be important for confirming the effectiveness of BCG instillation.

Long-term experience with early single mitomycin C instillations in patients with low-risk non-muscle-invasive bladder cancer: prospective, single-centre randomised trial.

PURPOSE: To study the benefits of a single, early, intravesical instillation of mitomycin C(MMC) after transurethral bladder resection (TURB) in patients with low-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: In this prospective randomised single-centre trial, 211 patients with primary and low-risk tumours were enrolled between 2000 and 2009. Patients were randomly allocated to receive MMC intravesically within 24 h of TUR or no further treatment. The primary end point was recurrence rate reduction. RESULTS: A total of 202 patients (97 in the MMC group and 105 in the control group) remained for analysis after exclusions. Median age was 61 years (IQR 42-78), and median follow-up was 90 months (IQR 3-112). No significant differences for patients' characteristics were observed between the two groups. During the study period, 10% (10/97) of the patients in the MMC group and 43% (46/105) in the control group experienced a recurrence (P = 0.0001). Four patients in the MMC group and 11 (P = 0.008) in the control group experienced an early recurrence (within 2 years). One patient in the control group presented a tumour progression (T2G3). MMC treatment was associated with a 31% absolute risk reduction of recurrence and a 3.26 numbers needed to treat to prevent one recurrence. CONCLUSIONS: In this single-centre, long-term follow-up, experience a single, early instillation of MMC after TUR for low-risk NMIBC is associated with a significant reduction in risk of early and late recurrences.

Bipolar transurethral resection of prostate: clinical and urodynamic evaluation.

OBJECTIVES: To report our experience with the clinical effectiveness of endoscopic resection of the prostate using the bipolar Gyrus PlasmaKinetic System. METHODS: A total of 120 patients with lower urinary tract symptoms were observed from 2002 to 2005. Of these 120 patients, 90 developed benign prostatic hyperplasia and were considered to have obstruction, and 51 of these 90 were scheduled for prostate surgery. The patients were randomized 1:1, using envelopes, into two groups: bipolar transurethral resection of the prostate (TURP) using the Gyrus PlasmaKinetic System (PK group) and monopolar TURP (standard TURP group). All patients were evaluated at baseline and follow-up (12 months after treatment) by medical history, International Prostate Symptom Score, inclusive of the question on quality of life, and physical examination, including digital rectal examination, transrectal ultrasonography, and pressure flow study. Statistical analysis was applied on the change in International Prostate Symptom Score and urodynamic parameters comparing the endpoints with baseline and comparing the baseline and follow-up characteristics between the two groups. RESULTS: The mean resection time was 39.1 minutes and 31.7 minutes for the PK and standard TURP groups, respectively (P = 0.437). The mean postoperative hemoglobin reduction at 24 hours of follow-up was 1.25 g/dL, with a 2.1% hematocrit reduction, in the PK group and 1.81 g/dL, with a 3.2% hematocrit reduction, in the standard TURP group (P = 0.716). Improvements in flow rate, International Prostate Symptom Score, quality-of-life score, and bladder outlet obstruction grade were comparable between the two groups. CONCLUSIONS: Bipolar TURP using the bipolar Gyrus PlasmaKinetic System seems to be a safe and effective procedure that is potentially associated with fewer side effects and could result in this procedure being more attractive for high-risk patients or, as recently proposed, for training purposes.

Molecular interactions between human cytochrome P450 1A2 and flavone derivatives.

Activation by human cytochrome P450 1A2 (hCYP1A2) of heterocyclic amines is assumed to trigger of a number of carcinogenic processes. In this work, a group of natural inhibitors of human cytochrome P450 1A2 reported in literature has been theoretically analysed. These consist of flavone hydroxylated derivatives, natural compounds that exist in plants and associated products. Different theoretical/computational tools were used to describe the specific molecular interactions between these compounds and hCYP1A2. Based on this analysis, a method is proposed for helping the selection of specific molecular features that enhance protein-inhibitor interaction.

Patients with bladder outlet obstruction who refuse treatment show no clinical and urodynamic change after long-term follow-up.

OBJECTIVE: To evaluate in patients with mild bladder outlet obstruction (BOO) who refused the proposed treatment and were on watchful waiting (WW), the symptomatic and urodynamic changes after 1-5 years of follow-up. METHODS: 102 patients with lower urinary tract symptoms (LUTS) and BOO (Schafer class: 2-6, median 3) were clinically and urodinamically re-evaluated after 1-5 years of follow-up. Of these, 82 were submitted to medical (alfuzosin or finasteride) or surgical treatment (prostatectomy or TUIP) and 20, who refused the proposed treatment, were on WW. A retrospective study was made on these 20 patients who underwent a second International Prostatic Symptom Score and pressure-flow evaluation after 1-5 years (median: 22 months) of watchful waiting. Wilcoxon matched-pairs signed-ranks test and Kruskal Wallis as appropriate were used for statistical analysis. RESULTS: In the group of patients who refused the proposed treatment, no statistically significant differences between the two evaluations were observed for any of the parameters investigated: International Prostatic Symptom Score (15.1 +/- 6.8; 14.7 +/- 7.5); maximum flow (11.5 +/- 4.2; 12.1 +/- 4.3); residual urine (90.2 +/- 154.5; 113.3 +/- 158.4); Schäfer class (2.9 +/- 0.9; 2.8 +/- 1.2); Urethral Resistance Algorithm (37.1 +/- 14.4; 37.3 +/- 16.3); Projected Isometric Pressure (113.7 +/- 26.5; 112.7 +/- 21.8). CONCLUSIONS: Patients with mild BOO may remain clinically and urodynamically stable for a long time.

Role of 99mTc-bombesin scan in diagnosis and staging of prostate cancer.

Aim of this work was to asses whether a novel 99mTc labeled Bombesin (BN) can play a clinical role in diagnosis and staging of prostate cancer. 14 patients were studied with trans-rectal ultrasonography-guided biopsy, CT and MRI and with 99mTc BN Scintigraphy. Five patients were also imaged by 111In Octreotide (O) scan. All the patients but one were submitted to surgery and final diagnosis was reached by pathology, taken as the gold standard method. Two patients showed benign adenoma and 12 patients showed cancer at biopsy. 99mTc BN SPECT was positive in all 12 patients with cancer. Four of these patients also showed pelvic focal uptake, referred to inguinal lymph-nodal involvement. MRI and CT provided similar findings in only three cases. Pathologic evaluation after operation confirmed the invasion of nodes in all four subjects. Both 99mTc BN and 111In O scans provided normal findings in the two subjects affected by benign adenoma, while 111In O was positive in only two of three patients with cancer and was always unable to detect nodal invasion. These preliminary data suggest that 99mTc BN SPECT scan could be useful to detect primary prostate cancer and to reveal loco-regional node involvement.

99mTc-bombesin detects prostate cancer and invasion of pelvic lymph nodes.

Biopsy is the standard method for the diagnosis of prostate cancer; however, it is inadequate for the assessment of lymph node invasion. Radionuclide imaging might be useful for both diagnosis and N staging, but it requires high uptake of radiotracers in order to overcome difficulties arising from the anatomy of the region. The aim of this study was to assess whether or not technetium-99m labelled bombesin (99mTc-BN) scan is able to detect prostate cancer and invasion of pelvic lymph nodes. Ten patients were studied with 99mTc-BN, transrectal ultrasonography, biopsy, computed tomography and magnetic resonance imaging. All the patients with cancer were operated on. Planar dynamic scintigraphy and single-photon emission tomography (SPET) were performed after administration of 185 MBq 99mTc-BN. Two patients showed benign adenoma and eight showed cancer at biopsy. The average Gleason's score was 7.5+/-1.3. 99mTc-BN dynamic planar scan showed hot spots in the prostatic fossa in two of the eight patients with cancer, both of whom had a prostate-specific antigen level higher than 20 ng/ml. In these patients, high uptake inside the prostatic fossa was detected as early as 1 min after injection, before the arrival of radioactivity in the bladder. True positive SPET scans were obtained in all eight patients with cancer. Invasion of the obturator nodes was detected by SPET in three patients, and in all three was confirmed at surgery. Our preliminary data encourage further studies on the prostate with 99mTc-BN. If the high sensitivity of 99mTc-BN SPET is confirmed, this method may play an important role in diagnosing and staging prostate cancer.

Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study.

A systematic analysis of both tumors and the surrounding urothelium to help identify what lies behind the mechanism of multifocal tumor development has not yet been performed. In this study we investigated chromosome 1, 7, 9, and 17 aneusomy in 25 superficial papillary carcinomas and in 51 tissue samples taken from sites of macroscopically uninvolved urothelium surrounding the tumors, using the fluorescence in situ hybridization method. Our data demonstrated a close genetic relationship between all examined tumors and normal-appearing mucosa. Numeric aberrations of chromosomes 1, 7, 9, and 17 were found to exhibit similar patterns in all analyzed specimens, although with different frequencies.

The evolution of detrusor overactivity after watchful waiting, medical therapy and surgery in patients with bladder outlet obstruction.

PURPOSE: We analyzed the evolution of detrusor overactivity in patients with bladder outlet obstruction treated with either medical or surgical therapy or watchful waiting. MATERIALS AND METHODS: Of 255 patients with symptomatic benign prostatic enlargement who completed the International Prostate Symptom Score and underwent full urodynamic investigation 161 presented with bladder outlet obstruction. Of the 161 men 101 were reevaluated with a second clinical evaluation and urodynamics 1 to 5 years (mean 2) after watchful waiting in 20, medical treatment (alfuzosin 20 and finasteride 16) in 36 and surgery (transurethral incision of the prostate 13 and prostatectomy 32) in 45. For statistical analysis Wilcoxon matched paired data and Kruskal Wallis tests were used as appropriate. RESULTS: Overall detrusor overactivity was present in 53 patients (52%) at baseline and 41 (40%) at followup. Detrusor overactivity was present in 9 patients (45%) at baseline and 11 (55%) at followup in the watchful waiting group (p = 0.17); 7 (35%) at baseline and 6 (30%) at followup in the alfuzosin group (p = 0.37); 10 (62.5%) at baseline and 10 at followup in the finasteride group (p = 1); 6 (46%) at baseline and 4 (30%) at followup in the transurethral prostate incision group (p = 0.48); and 21 (68%) at baseline and 10 (31%) at followup in the prostatectomy group (p = 0.02). CONCLUSIONS: Detrusor overactivity is highly prevalent (52%) in patients with bladder outlet obstruction, and appears to persist for long periods when obstruction is left untreated or treated only with medical therapy. However, surgical treatment of bladder outlet obstruction, prostatectomy in particular, significantly reduces the incidence of detrusor overactivity and lessens the chance of its de novo appearance for up to 5 years.