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Purpose: The dogma that urine is sterile has been overturned and dysbiosis of the urinary microbiome has been linked to many urological disorders. We tested the hypothesis that the urinary microbial composition may be different between men with or without bladder cancer in catheter collected urines, bladder washouts and midstream voided urines, and may be dependent on tumor staging., Materials and Methods: Liquid samples were collected from male patients with bladder cancer, and sex and age matched nonneoplastic controls. Total DNA was extracted and processed for 16S rRNA gene sequencing. Bioinformatic analysis for microbial classification was performed to assess diversity and variations., Results: The urinary microbiome associated with catheter collected urine samples of patients with bladder cancer was characterized by a significantly increased abundance of Veillonella (p=0.04) and Corynebacterium (p=0.03), and decreased Ruminococcus (p=0.03) compared to controls, with differences exacerbating with disease progression. Compared to catheterized urines, bladder cancer washouts showed the specific increase of some taxa, like Burkholderiaceae (p=0.014), whereas midstream urines were enriched in Streptococcus (p <0.0001), Enterococcus (p <0.0001), Corynebacterium (p=0.038) and Fusobacterium (p <0.0001)., Conclusions: The bladder is colonized by endogenous bacteria and microbial modifications characterize the microbiome of patients with bladder cancer. Different microbial compositions can be characterized by changing sampling strategy. These results pave the way for exploring new diagnostic and therapeutic options based on the manipulation of the bacterial community.

Purpose: We investigated whether tissue engineered material may be adopted using standard techniques for anterior urethroplasty., Materials and Methods: We performed a retrospective multicenter study in patients with recurrent strictures, excluding those with failed hypospadias, lichen sclerosus, traumatic and posterior strictures. A 0.5 cm 2 oral mucosa biopsy was taken from the patient cheek and sent to the laboratory to manufacture the graft. After 3 weeks the tissue engineered oral mucosal MukoCell® graft was sent to the hospital for urethroplasty. Four techniques were used, including ventral onlay, dorsal onlay, dorsal inlay and a combined technique. Cystourethrography was performed 1 month postoperatively. Patients underwent clinical evaluation, uroflowmetry and post-void residual urine measurement every 6 months. When the patient showed obstructive symptoms, defined as maximum urine flow less than 12 ml per second, the urethrography was repeated. Patients who underwent further treatment for recurrent stricture were classified as having treatment failure., Results: Of the 38 patients with a median age of 57 years who were included in study the strictures were penile in 3 (7.9%), bulbar in 29 (76.3%) and penobulbar in 6 (15.8%). Median stricture length was 5 cm and median followup was 55 months. Treatment succeeded in 32 of the 38 patients (84.2%) and failed in 15.8%. Success was achieved in 85.7% of ventral onlay, 83.3% of dorsal onlay, 80% of dorsal inlay and 100% of combined technique cases. No local or systemic adverse reactions due to the engineered material were noted., Conclusions: Our findings show that a tissue engineered oral mucosa graft can be implanted using the same techniques suggested for anterior urethroplasty and native oral mucosa, and guaranteeing a similar success rate., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging., Materials and Methods: In this prospective observational study we analyzed 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68 Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater)., Results: A total of 45 patients with a median age of 64 years were referred for 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum-to-background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum-to-background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum-to-background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively., Conclusions: Our findings support the use of 68 Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated predictive factors of failure and performed a resource consumption analysis in patients who underwent active surveillance for nonmuscle invasive bladder cancer., Materials and Methods: This prospective observational study monitored patients with a history of pathologically confirmed stage pTa (grade 1-2) or pT1a (grade 2) nonmuscle invasive bladder cancer, and recurrent small size and number of tumors without hematuria and positive urine cytology. The primary end point was the failure rate of active surveillance. Assessment of failure predictive variables and per year direct hospital resource consumption analysis were secondary outcomes. Descriptive statistical analysis and Cox regression with univariable and multivariable analysis were done., Results: Of 625 patients with nonmuscle invasive bladder cancer 122 with a total of 146 active surveillance events were included in the protocol. Of the events 59 (40.4%) were deemed to require treatment after entering active surveillance. Median time on active surveillance was 11 months (IQR 5-26). Currently 76 patients (62.3%) remain under observation. On univariable analysis only time from the first transurethral resection to the start of active surveillance seemed to be inversely associated with recurrence-free survival (HR 0.99, 95% CI 0.98-1.00, p = 0.027). Multivariable analysis also revealed an association with age at active surveillance start (HR 0.97, 95% CI 0.94-1.00, p = 0.031) and the size of the lesion at the first transurethral resection (HR 1.55, 95% CI 1.06-2.27, p = 0.025). The average specific annual resource consumption savings for each avoided transurethral bladder tumor resection was €1,378 for each intervention avoided., Conclusions: Active surveillance might be a reasonable clinical and cost-effective strategy in patients who present with small, low grade pTa/pT1a recurrent papillary bladder tumors., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Few randomized, controlled trials have compared standard abdominal sacrocolpopexy and the laparoscopic approach. We tested the hypothesis that laparoscopic sacrocolpopexy could compete with abdominal sacrocolpopexy for pelvic organ prolapse repair., Materials and Methods: This randomized, controlled trial was done to compare laparoscopic sacrocolpopexy and abdominal sacrocolpopexy for pelvic organ prolapse repair in women referred to our tertiary Department of Urology for symptomatic stage 2 or greater pelvic organ prolapse. The primary outcome was quantitative evaluation by the POP-Q (Pelvic Organ Prolapse Quantification) system. Cure was defined as prolapse stage 1 or less, point C/D -5 or less at the apex and at least 7 cm total vaginal length. Secondary outcomes were the complication rate, operative time, intraoperative blood loss, hospital stay and PGI-I (Patient Global Impression of Improvement) scores. The Kaplan-Meier estimator with the log-rank test was used to estimate pelvic organ prolapse recurrence-free survival rates., Results: A total of 200 patients were eligible for study. We compared 60 and 61 patients treated with abdominal and laparoscopic sacrocolpopexy, respectively. At a mean followup of 41.7 months the cure rate was of 100% for both approaches. Kaplan-Meier curves showed that overall pelvic organ prolapse recurrence-free survival was longer following the open approach. Patients treated with laparoscopic sacrocolpopexy showed significantly earlier recurrence (p = 0.030), mostly in the first 12 months after surgery. When evaluating the different compartments, a statistically significant difference was observed between the laparoscopic and abdominal approaches for anterior compartment descensus (11 vs 1, p = 0.004). Statistical results had high internal validity but may not be applicable to other populations or settings., Conclusions: Laparoscopic sacrocolpopexy provides outcomes as good as those of abdominal sacrocolpopexy for anatomical correction but not for anterior pelvic organ prolapse., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated deterioration of the success rate of penile and bulbar substitution urethroplasty., Materials and Methods: We performed a retrospective descriptive analysis of patients who underwent substitution urethroplasty between July 1994 and September 2007. Inclusion criteria included 1-stage anterior urethroplasty using penile skin or oral mucosa with a minimum of 6 years followup. Patients with posterior urethral stricture, failed hypospadias or incomplete clinical records were excluded from analysis. The primary study outcome was postoperative failure-free survival and the secondary outcome was to identify significant predictors of treatment failure. The clinical outcome was considered a failure when any postoperative instrumentation was needed. Descriptive statistical analysis was done as well as Kaplan-Meier analysis, and univariable and multivariable Cox regression analysis., Results: A total of 359 patients were included in study. Median followup was 118 months. Of the procedures 265 (73.8%) were successful and 94 (26.2%) failed, including 91 (96.8%) within the first 5 years. Substitute tissue type (oral mucosa vs skin) was the only significant predictor on univariable analysis (HR 1.86, p = 0.005). This result was confirmed by multivariable analysis adjusting for age at surgery, stricture length and etiology, urethroplasty type and previous treatments (HR 2.26, p = 0.001)., Conclusions: Deterioration after anterior 1-stage substitution urethroplasty seems to develop within the first 5 years. Oral mucosa showed greater failure-free survival than penile skin and 1-stage penile urethroplasty showed the same success rate as bulbar urethroplasty., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated the early and late complications after oral mucosal graft harvesting, and reported the independent predictors of outcome via multivariable analysis., Materials and Methods: We performed a retrospective descriptive study of 553 patients from whom an oral mucosa graft was harvested for urethroplasty from single or bilateral cheeks. Patients who underwent oral mucosa harvesting from the lip, the tongue or from the cheek and lip at the same time were excluded from analysis. The oral graft was harvested in an ovoid shape with closure of the wound. Postoperative early and late complications were investigated using a self-administered, nonvalidated, semiquantitative questionnaire. There were 6 questions on early complications, and 13 questions investigated late complications and patient satisfaction., Results: Descriptive statistics of categorical variables focused on frequencies and proportions. Univariable and multivariable analyses were used to predict early and late dissatisfaction of patients. Bleeding was reported in 3.4% of patients. Overall 53.2% of patients did not report any pain and 36.3% reported no swelling. Late complications analysis showed that 95.5% of patients declared that the surgical closure of the wound did not cause any difficulty in opening the mouth or problems with smiling (98.2%) and/or dry mouth (95.8%). Overall 98.2% of patients were satisfied with the procedure. Univariable and multivariable analyses revealed that bilateral graft harvesting was the only significant predictor of patient dissatisfaction (OR 2.85, p = 0.01 and OR 2.72, p = 0.02; respectively)., Conclusions: Harvesting the oral mucosa ovoid graft from a single cheek with closure of the wound is a safe procedure with high rates of patient satisfaction., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3., Materials and Methods: We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models., Results: Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model., Conclusions: PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We developed and validated a Prostate Health Index (Beckman Coulter, Brea, California) based nomogram to predict prostate cancer at extended prostate biopsy., Materials and Methods: The study population consisted of 729 patients who were scheduled for prostate biopsy following suspicious digital rectal examination and/or increased prostate specific antigen. Total and free prostate specific antigen, percent free-to-total prostate specific antigen, [-2]proPSA and the prostate health index [([-2]proPSA/free prostate specific antigen) × √total prostate specific antigen)] were determined. Logistic regression models were fitted to test prostate cancer predictors. Predictive accuracy estimates of biopsy outcome predictions were quantified. Regression coefficients were used to create a decision making tool to predict prostate cancer. A calibration plot was used to evaluate the extent of overestimating or underestimating the observed prostate cancer rate. Decision curve analysis provided an estimate of the net benefit obtained using the prostate health index based nomogram., Results: Overall 280 of 729 patients (38.4%) were diagnosed with prostate cancer at extended prostate biopsy. On accuracy analyses prostate health index emerged as the most informative predictor of prostate cancer (AUC 0.70) compared to established predictors, such as total prostate specific antigen (0.51) and percent free-to-total prostate specific antigen (0.62). Including the prostate health index in a multivariable logistic regression model based on patient age, prostate volume, digital rectal examination and biopsy history significantly increased predictive accuracy by 7% from 0.73 to 0.80 (p <0.001). Nomogram calibration was good. Decision curve analysis showed that using the prostate health index based nomogram resulted in the highest net benefit., Conclusions: The prostate health index based nomogram can assist clinicians in the decision to perform biopsy by providing an accurate estimation of an individual risk of prostate cancer., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We tested the hypothesis that serum isoform [-2]proPSA derivatives %p2PSA and Prostate Health Index are accurate predictors of prostate cancer in men scheduled for repeat biopsy., Materials and Methods: The study was an observational prospective evaluation of a clinical cohort of men with 1 or 2 previous negative prostate biopsies, with persistent suspicion of prostate cancer. They were enrolled in the study to determine the diagnostic accuracy of %p2PSA using the formula, (p2PSA pg/ml)/(free prostate specific antigen ng/ml × 1,000)]× 100, and Beckman-Coulter Prostate Health Index using the formula, (p2PSA/free prostate specific antigen) × √total prostate specific antigen), and to compare it with the accuracy of established prostate cancer serum tests (total prostate specific antigen, free prostate specific antigen and percent free prostate specific antigen). Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis., Results: Prostate cancer was found in 71 of 222 (31.9%) subjects. %p2PSA and Prostate Health Index were the most accurate predictors of disease. %p2PSA significantly outperformed total prostate specific antigen, free prostate specific antigen, percent free prostate specific antigen and p2PSA in the prediction of prostate cancer (p ≤0.01), but not Prostate Health Index (p = 0.094). Prostate Health Index significantly outperformed total prostate specific antigen and p2PSA (p ≤0.001) but not free prostate specific antigen (p = 0.109) and free/total prostate specific antigen (p = 0.136). In multivariable logistic regression models %p2PSA and Prostate Health Index achieved independent predictor status, and significantly increased the accuracy of multivariable models including prostate specific antigen and prostate volume with or without percent free prostate specific antigen and prostate specific antigen density by 8% to 11% (p ≤0.034). At a %p2PSA cutoff of 1.23, 153 (68.9%) biopsies could have been avoided, missing prostate cancer in 6 patients. At a Prostate Health Index cutoff of 28.8, 116 (52.25%) biopsies could have been avoided, missing prostate cancer in 6 patients., Conclusions: Serum %p2PSA and Prostate Health Index are more accurate than standard reference tests in predicting repeat prostate biopsy outcome, and could avoid unnecessary repeat biopsies., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Using pathological examination we evaluated the involvement of lichen sclerosus in urethral strictures in men., Materials and Methods: We performed an observational, descriptive, retrospective study of patients treated for genital lichen sclerosus who had at least 1 biopsy positive for lichen sclerosus. Study exclusion criteria were malignant penile lesions, incomplete data on personal charts and biopsies negative for lichen sclerosus. Preoperative evaluation included clinical history, physical examination, urine culture, post-void residual urine measurement, uroflowmetry and urethrography. Biopsies were taken from the foreskin, penile skin, glans, urethral meatus, mucosa of the navicularis, and penile and bulbar urethra to confirm the lichen sclerosus diagnosis and spread of the disease through the urethra. Patients were classified into 5 groups by surgical procedure., Results: Included in the study were 99 patients with a median age of 46 years who were diagnosed with genital lichen sclerosus. Of 274 biopsies 234 (85.4%) were positive for lichen sclerosus. Group 1 included 39 patients who underwent circumcision, group 2 included 15 who underwent meatotomy, group 3 included 15 who underwent navicularis urethroplasty, group 4 included 17 who underwent penile urethroplasty and group 5 included 13 who underwent perineal urethrostomy. Lichen sclerosus was documented by histology in the meatus in 91.5% of cases, in the navicularis in 84.4% and in the penile urethra in 70.6%. All biopsies from the bulbar urethra were negative., Conclusions: Involvement of lichen sclerosus through the navicularis and penile urethra was documented. No sign of lichen sclerosus was found in the bulbar urethra., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We reevaluated and brought up to date the 8-year followup of a previous published, randomized, controlled trial of the impact of Burch colposuspension as a prophylactic anti-incontinence procedure in patients without urinary incontinence who underwent abdominal pelvic organ prolapse repair., Materials and Methods: A total of 66 continent women with pelvic organ prolapse were randomly assigned to abdominal pelvic organ prolapse repair and concomitant Burch colposuspension in 34 (group 1) or pelvic organ prolapse repair alone without an anti-incontinence procedure in 32 (group 2). Primary study end points were the anatomical outcome and changes in incontinence status. Secondary end points were changes in subjective symptoms and quality of life., Results: Median followup was 97 months (range 72 to 134). Three group 1 and 1 group 2 patients were lost to followup. Three group 1 patients had a stage I rectocele and 1 had a stage I cystocele. Four group 2 patients had a stage I rectocele and 3 had a stage I cystocele. Nine of 31 group 1 patients (29%) were incontinent compared with 5 of 31 (16%) in group 2 (p = 0.553). In group 1 all except 1 patient were successfully treated for voiding dysfunction. Storage symptoms had disappeared in 1 patient and de novo storage symptoms had developed in 2 since the previous followup. De novo incontinence developed in 2 group 2 patients after midterm outcomes were reported. Median Urogenital Distress Inventory-6 and Incontinence Impact on Quality of Life-7 scores were improved in all groups at last followup (p 0.0001)., Conclusions: Long-term results cast doubt on whether Burch colposuspension should be done during pelvic organ prolapse repair in continent women., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We present a new, 2-stage functional and cosmetic reconstruction of concealed penis in adults with short-term subjective outcomes., Materials and Methods: Patients with excess penile skin removal, shaft tissue scarring and penile retraction with poor functional and cosmetic results underwent 2-stage repair. At stage 1 after a coronal incision and penile degloving an intrascrotal tunnel was formed and the penis was transposed through the scrotum. Three or 4 zero or 2-zero nonresorbable sutures were applied ventral to the penis, crossing through the entire scrotum to ensure complete scrotal skin adhesion to the penis (penile scrotalization). At stage 2 after 6 to 12 weeks the scrotal skin at the penile base was incised bilaterally to separate the skin around the penis from the remaining scrotal skin (penile descrotalization). Evaluation was scheduled 3, 6 and 9 months postoperatively, and annually thereafter., Results: Ten men with concealed penis underwent this 2-stage penile repair, including 8 who were circumcised and 2 who underwent conservative surgery for penile cancer. Mean +/- SD operative time was 75 +/- 15 minutes for stage 1 and 45 +/- 10 minutes for stage 2. No major intraoperative or perioperative complications occurred except superficial scrotal hematoma in 1 patient. At a median followup of 20 months (range 6 to 72) all men were in satisfactory clinical condition and the median patient satisfaction visual analog score was 97 (range 85 to 100). All patients recovered normal spontaneous erection with regular sexual intercourse 4 to 8 weeks after operation 2., Conclusions: This simple, new 2-stage technique seems feasible and effective, and it is well accepted by patients. Further studies are mandatory to confirm preliminary results., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We compared posterior urethral strictures after pelvic fracture urethral distraction defects in India and Italy., Materials and Methods: We retrospectively analyzed the records of patients in India and Italy who underwent repair for posterior urethral stricture after pelvic fracture urethral distraction defect. We investigated etiology, emergency treatment type, the specialist involved in emergency treatment, the type of stricture resulting from trauma and primary repair, posterior urethroplasty techniques and results., Results: Of 255 patients with a median age of 33 years 117 (45.8%) and 138 (54.2%) were evaluated in India and Italy, respectively. In India the most common causes of pelvic fracture urethral distraction defects were pedestrian (35%), motorcycle (26.5%) and bicycle (12.8%) accidents. The most common emergency treatment was suprapubic cystostomy (79.5% of cases). Of the patients 70.1% were treated in emergency fashion by a surgeon and 85.4% had complex posterior urethral strictures. The most common technique was anastomosis with inferior and total pubectomy in 56.4% and 15.3% of cases, respectively. In Italy the etiology was mainly automobile accidents (39.2%). The most common emergency treatment was endoscopic realignment (49.2% of cases). Of the patients 92.7% were treated in emergency fashion by a urologist and 68.1% had simple urethral strictures. Perineal anastomosis and laser urethrotomy were the most used techniques (38.4% and 21.1% of cases, respectively). In India 92 cases (78.6%) were successful and 25 (21.4%) failed while in Italy 120 (86.9%) were successful and 18 (13.1%) failed. Median followup was 74 months (range 12 to 239)., Conclusions: Differences in emergency treatment for pelvic fracture urethral distraction defects influence the choice of delayed posterior repair and results., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To our knowledge epidemiological data on the incidence of failed hypospadias repair and the number of patients seeking further surgical treatment remain unknown. We report an observational, descriptive survey of patients who were evaluated and treated for urethral stricture disease and/or penile defects after primary hypospadias repair., Materials and Methods: We performed a retrospective observational chart analysis of patients evaluated and treated for urethral stricture disease and/or penile defects at 2 tertiary European centers from January 1998 to December 2007. In each case we investigated the primary abnormal meatal site, the number of operations needed to repair primary hypospadias and complications of this primary repair. Patients were offered surgical repair for previous failed hypospadias treatment. After surgery evaluation was scheduled at 3, 6 and 9 months. Success was defined as a functional urethra without fistula, stricture or residual chordee and a cosmetically acceptable glanular meatus after the completion of all secondary procedures., Results: A total of 1,176 patients with a mean age of 31 years were evaluated and treated. To treat failed hypospadias repair 760 (64.6%) and 416 patients (35.4%) underwent 1-stage and staged repair, respectively. Mean followup was 60.4 months. Of 1,176 cases 1,036 (88.1%) were classified as successful and 140 (11.9%) were considered failures., Conclusions: Failed hypospadias repair may be corrected by multiple and complex surgeries. Its effects are experienced during the lifetime of the patient and parents.

Purpose: We performed a quality of life assessment for patients treated with perineal urethrostomy for anterior urethral stricture disease., Materials and Methods: We retrospectively reviewed 173 patients (median age 55 years) who underwent perineal urethrostomy (from 1978 to 2007) as part of a plan for a staged urethroplasty repair for a complex anterior urethral stricture. The perineostomy was made using flap urethroplasty. The clinical outcome was considered a failure when postoperative instrumentation was needed. A questionnaire was used to evaluate patient quality of life and satisfaction., Results: Stricture etiology was unknown in 50.3% of the cases, lichen sclerosus in 17.3%, catheter in 13.3%, instrumentation in 8.7%, failed hypospadias repair in 4.6%, trauma in 4.1% and infection in 1.7%. Stricture length was 1 to less than 2 cm in 1.2% of cases, 2 to less than 3 cm in 3.5%, 3 to less than 4 cm in 12.1%, 4 to less than 5 cm in 13.8%, 5 to less than 6 cm in 7.5%, greater than 6 cm in 4.1% and panurethral in 57.8%. Of 173 patients 91 (52.6%) underwent prior urethroplasty. Median followup length was 62 months (range 12 to 361). Of 173 cases 121 (70%) were successful and 52 (30%) were failures, requiring revision of the perineostomy. Of 173 patients 135 (78%) were satisfied with the results obtained with surgery, 33 (19.1%) were very satisfied, 127 (73.4%) with a median age of 57 years (range 23 to 85) refused to do the second stage of urethroplasty and 46 (26.6%) with a median age of 47.5 years (range 27 to 72) are currently on a waiting list for the second stage of urethroplasty., Conclusions: Perineostomy is a necessary procedure for patients with complex urethral pathology and satisfaction rates are high.

Purpose: We evaluated the impact of Burch colposuspension as an anti-incontinence measure in patients with urinary incontinence undergoing abdominal surgery for pelvic organ prolapse repair., Materials and Methods: A total of 47 women with pelvic organ prolapse and urinary incontinence were randomly assigned to abdominal pelvic organ prolapse repair and concomitant Burch colposuspension (24 patients, group A) or pelvic organ prolapse repair alone without an anti-incontinence procedure (23 patients, group B). They were followed up at 3, 6 and 9 months after surgery, and then annually. The primary outcome measures were anatomical outcome and changes in incontinence status as indicated by a bladder diary, the number of daily pads and the stress test. Secondary end points were changes in subjective symptoms and quality of life as measured by the Urogenital Distress Inventory and the Incontinence Impact Questionnaire., Results: In group A 13 of 24 patients (54.2%) were still incontinent after surgery compared with 9 of 23 (39.1%) in group B. The intragroup difference was significant (group A p = 0.003, group B p = 0.0001), but there was no significant intergroup difference (p = 0.459 for A vs B). No significant intergroup difference emerged in anatomical outcome. Urogenital Distress Inventory and Incontinence Impact Questionnaire scores improved in both groups (p = 0.0001) but the intergroup difference was not significant in either questionnaire (p = 0.769 and p = 0.327, respectively)., Conclusions: Burch colposuspension does not provide any additional benefit in pelvic organ prolapse repair in patients with urinary incontinence.

Purpose: We performed a retrospective evaluation and statistical analysis of outcome in patients who underwent bulbar end-to-end anastomosis., Materials and Methods: We reviewed 153 patients with an average age of 39 years who underwent bulbar end-to-end anastomosis between 1988 and 2006. Mean followup was 68 months. Stricture etiology was unknown (62.7%), catheter (14.4%), blunt perineal trauma (11.7%), instrumentation (9.8%), radiotherapy (0.7%) and infection (0.7%). Stricture length was 1 to 2 cm (in 59.5%), 2 to 3 cm (37.9%), 3 to 4 cm (1.9%) or 4 to 5 cm (0.7%). A total of 90 patients (59%) underwent dilation, internal urethrotomy, urethroplasty or multiple procedures before being referred to our center. Clinical outcome was considered a treatment failure when any postoperative instrumentation was needed. The prevalence of postoperative sexual dysfunction was investigated using a nonvalidated questionnaire., Results: Of 153 cases 139 (90.8%) were successful and 14 (9.2%) were treatment failures. Treatment failure was managed with urethrotomy in 9 cases, end-to-end anastomosis in 2, buccal mucosal graft urethroplasty in 1 and 2-stage repair in 2. Of 14 cases of failure 12 had a satisfactory final outcome, 1 is still waiting for the second stage of urethroplasty and 1 underwent definitive perineostomy. There were 14 patients (23.3%) who experienced ejaculatory dysfunction, 1 (1.6%) a cold glans during erection, 7 (11.6%) a glans that was neither full nor swollen during erection and 11 (18.3%) had decreased glans sensitivity. No patients complained of penile chordee or impotence., Conclusions: Bulbar end-to-end anastomosis has a success rate of 90.8%. Most patients were satisfied with the surgical outcome despite postoperative complications such as ejaculatory dysfunction, a glans that was neither full nor swollen during erection, or decreased penile sensitivity.

Purpose: We studied the feasibility, safety and efficacy of daily intravesical instillation of 1 mg of the endogenous peptide nociceptin/orphanin FQ in a selected group of patients who perform clean intermittent self-catheterization for neurogenic detrusor overactivity incontinence., Materials and Methods: A total of 18 patients with neurogenic detrusor overactivity incontinence and on clean intermittent self-catheterization were prospectively randomized to receive 1 mg nociceptin/orphanin FQ in 10 cc saline (9) or placebo (saline) solution (9) at the first morning catheterization for 10 days. All patients completed a voiding diary using a frequency/volume chart according to International Continence Society guidelines, and reported daily incontinence frequency. Mean changes in incontinence episode frequency and voiding diary mean bladder capacity from baseline throughout treatment were the primary outcome variables. Urodynamic parameters (cystomanometric bladder capacity, maximum bladder pressure) were also recorded at baseline and during the study., Results: The 2 groups were well balanced and all patients completed the study. The urodynamic parameters recorded during the study showed an increase in cystomanometric bladder capacity and a decrease in maximum bladder pressure compared to baseline only in patients assigned to the nociceptin/orphanin FQ group. Mean daily urine leakage episodes during nociceptin/orphanin FQ treatment were 0.94 vs a pretreatment baseline of 2.18 (p < 0.05), while no significant changes were reported in the placebo group (2.06 vs 2.43 baseline). The total mean voiding diary bladder capacity increased from 171 +/- 70 to 294 +/- 107 ml in patients receiving nociceptin/orphanin FQ, while voiding diary mean bladder capacity remained unchanged in patients receiving placebo (from 182 +/- 55 to 178 +/- 23 ml). No significant problems related to feasibility of the procedure as well as significant side effects were reported by patients., Conclusions: This study showed that intravesical nociceptin/orphanin FQ but not placebo inhibited the micturition reflex in patients with neurogenic detrusor overactivity incontinence, and demonstrated the clinical efficacy of nociceptin/orphanin FQ during 10 days of treatment. These findings support the use of nociceptin/orphanin FQ peptide receptor agonists as an innovative therapeutic approach for controlling detrusor overactivity incontinence.

Purpose: We retrospectively reviewed patterns of failure after bulbar substitution urethroplasty. In particular we investigated the prevalence and location of anastomotic fibrous ring strictures occurring at the apical anastomoses between the graft and urethral plate after 3 types of onlay graft techniques., Materials and Methods: We reviewed the records of 107 patients who underwent bulbar urethroplasty between 1994 and 2004. Mean patient age was 44 years. Patients with lichen sclerosus, failed hypospadias repair or urethroplasty and panurethral strictures were excluded. A total of 45 patients underwent dorsal onlay skin graft urethroplasty, 50 underwent buccal mucosa onlay graft urethroplasty and 12 underwent augmented end-to-end urethroplasty. The clinical outcome was considered a success or failure at the time that any postoperative procedure was needed, including dilation. Mean followup was 74 months (range 12 to 130)., Results: Of 107 cases 85 (80%) were successful and 22 (20%) failed. Failure in 12 patients (11%) involved the whole grafted area and in 10 (9%) it involved the anastomotic site, which was distal and proximal in 5 each. Urethrography, urethral ultrasound and urethroscopy were fundamental for determining the difference between full-length and focal extension of re-stricture. Failures were treated with multistage urethroplasty in 12 cases, urethrotomy in 7 and 1-stage urethroplasty in 3. Of the patients 16 had a satisfactory final outcome and 6 underwent definitive perineal urinary diversion., Conclusions: The prevalence and location of anastomotic ring strictures after bulbar urethroplasty were uniformly distributed in after 3 surgical techniques using skin or buccal mucosa. Further studies are necessary to clarify the etiology of these fibrous ring strictures.

Purpose: The use of buccal mucosa graft onlay urethroplasty represents the most widespread method of bulbar urethral stricture repair. The graft may be placed on the ventral or dorsal urethral surface according to surgeon experience and preference. We investigated whether the results are affected by the surgical technique by comparing the outcome of 3 types of bulbar urethroplasty using buccal mucosa graft., Material and Methods: We repaired 50 bulbar urethral strictures with buccal mucosa grafts from 1997 to 2002. Mean patient age was 42 years. The etiology of stricture was ischemia in 12 cases, trauma in 6, instrumentation in 4 and unknown in 28. Patients with lichen sclerosus, failed hypospadias or urethroplasty and stricture extending into the penile urethra were not included. A total of 47 patients (94%) had undergone previous urethrotomy or dilation. The buccal mucosa graft was always harvested from the cheek using a 2 team approach. Mean graft length was 4.2 cm. The graft was placed on the ventral, dorsal and lateral bulbar urethral surface in 17, 27 and 6 cases, respectively. Clinical outcome was considered a success or failure at the time that any postoperative procedure was needed, including dilation. Mean followup was 42 months (range 12 to 76)., Results: Of 50 cases 42 (84%) were successful and 8 (16%) failed. The 17 ventral grafts provided success in 14 cases (83%) and failure in 3 (17%). The 27 dorsal grafts provided success in 23 cases (85%) and failure in 4 (15%). The 6 lateral grafts provided success in 5 cases (83%) and failure in 1 (17%). No surgical complications were observed. Failures involved the anastomotic site (distal in 2 and proximal in 3) and the whole grafted area in 3 cases. They were treated with urethrotomy in 5 cases and 2-stage urethroplasty in 3., Conclusions: In our experience the placement of buccal mucosa grafts into the ventral, dorsal or lateral surface of the bulbar urethra showed the same success rates (83% to 85%) and the outcome was not affected by the surgical technique. Moreover, stricture recurrence was uniformly distributed in all patients.

Purpose: Previously buccal mucosal grafts used for repairing adult bulbourethral stricture with the 1-stage dorsal technique has provided a satisfactory outcome in our experience. We present the wider use of buccal mucosal grafts for 2-stage urethroplasty., Materials and Methods: A total of 24 men 25 to 60 years old (median age 45) with a complex bulbar stricture underwent 2-stage urethroplasty using a buccal mucosal graft to repair the perineostomy. The primary etiology of stricture was traumatic in 4 cases, inflammatory in 16 and unknown in 4. The 2 x 6 cm. graft was harvested from the inner cheek and sutured to the left margin of the urethral mucosal plate with running 6-zero polyglactin suture. Patients were discharged from the hospital within 3 days with a 14Fr silicone urethral catheter in place. Radiological studies and urethroscopy were done 1 year after closure., Results: A final successful outcome with no recurrent stricture was achieved in 23 of 24 men (92.8%) at a median followup of 18 months (range 13 to 32). In 1 case a urethrocutaneous fistula at the initial radiological assessment closed spontaneously after 14 days of catheterization. No urethral diverticula developed. The mean postoperative peak flow rate is 22 ml. per second (range 18 to 25)., Conclusions: Our new 2-stage buccal mucosal graft urethroplasty may be an excellent technique for complex bulbar urethral stricture disease. Our suggestions may increase usefulness of the 2-stage technique for repairing complex strictures due to the avoidance of classic complications.

Purpose: Management of neurogenic incontinence is complex and available treatments are not satisfactory. Nociceptin/orphanin FQ, a recently discovered neuropeptide, has been reported to inhibit the voiding reflex in the rat. These experimental results prompted us to investigate the urodynamic and clinical effects of intravesical instillation of nociceptin/orphanin FQ in humans., Material and Methods: Our study involved 5 normal subjects (group 1) with a mean age of 40.4 years (range 21 to 54) and 9 patients (group 2) 40.4 years (24 to 54). All patients in group 2 presented with detrusor hyperreflexia refractory to standard therapy. They were invited to undergo a filling cystometrogram with saline solution and after 30 minutes, a new one with a solution containing 1 microM. nociceptin/orphanin FQ. The urodynamic parameters that were recorded included bladder capacity, volume threshold for the appearance of detrusor hyperreflexia and maximum bladder pressure. Clinical and urodynamic followup was performed after 15 days. The data were statistically analyzed with 1-way analysis of variance followed by the Dunnett test for multiple comparison considered statistically significant with p <0.05., Results: Intravesical instillation of 1 microM. nociceptin/orphanin FQ in group 1 did not produce significant functional changes. This infusion in group 2 produced a statistically significant increase in mean bladder capacity and volume threshold for the appearance of detrusor hyperreflexia from 164 plus or minus standard deviation (SD) 84 to 301 +/- 118 and 93 plus or minus SD 41 to 231 +/- 104 ml. (p <0.05, respectively). Mean maximum bladder pressure decreased from 79 plus or minus SD 25 to 54 +/- 44 cm. water but was not statistically significant (p = 0.19). After 15 days an absence of clinical improvement was noticed in group 2, and the urodynamic control did not show any significant changes compared to the values before nociceptin/orphanin FQ treatment. No severe symptomatic reactions were observed during infusion of 1 microM. nociceptin/orphanin FQ., Conclusions: Our results demonstrate that nociceptin/orphanin FQ is able to elicit a robust inhibitory effect on voiding reflex in group 2 but not 1. The ideal dosage, route of administration of nociceptin/orphanin FQ and treatment interval are not yet established.

Purpose: A urethral stricture recurring after repeat urethrotomy challenges even a skilled urologist. To address the question of whether to repeat urethrotomy or perform open reconstructive surgery, we retrospectively review a series of 93 patients comparing those who underwent primary repair versus those who had undergone urethrotomy and underwent secondary treatment., Materials and Methods: From 1975 to 1998, 93 males between age 13 and 78 years (mean 39) underwent surgical treatment for bulbar urethral stricture. In 46 (49%) of the patients urethroplasty was performed as primary repair, and in 47 (51%) after previously failed urethrotomy. The strictures were localized in the bulbous urethra without involvement of penile or membranous tracts. The etiology was ischemic in 37 patients, traumatic in 23, unknown in 17 and inflammatory in 16. To simplify evaluation of the results, the clinical outcome was considered either a success or a failure at the time any postoperative procedure was needed, including dilation., Results: In our 93 patients primary urethroplasty had a final success rate of 85%, and after failed urethrotomy 87%. Previously failed urethrotomy did not influence the long-term outcome of urethroplasty. The long-term results of different urethroplasty techniques had a final success rate ranging from 77% to 96%., Conclusions: We conclude that failed urethrotomy does not condition the long-term result of surgical repair. With extended followup, the success rate of urethroplasty decreases with time but it is in fact still higher than that of urethrotomy.

Purpose: The major obstacle to successful discordant kidney xenotransplantation is hyperacute rejection (HAR). Complement plays a key role in the induction of HRA, defined by endothelial cell activation, loss of vascular integrity, hemorrhage and thrombosis. The activation of complement is tightly controlled by a number of species-specific regulatory proteins which inhibit, at different points, the cascade of events leading to the formation of the membrane attack complex (MAC). We have tested the hypothesis that kidneys derived from transgenic mice expressing two human complement inhibitors, Decay Accelerating Factor (hDAF) and Membrane Cofactor Protein (MCP), could be protected from human complement-mediated damage., Materials and Methods: Control and transgenic mice were perfused with human plasma by cannulation of the right jugular vein, at a perfusion rate of 10 microL./min. for two hours. Complement C3 deposition was detected on kidney sections by immunohistochemistry using specific FITC antibody. Complement-induced tissue damage was evaluated by histopathological examination., Results: Heavy deposition of complement C3 was observed on kidneys derived from perfused control mice. This was associated with a characteristic HAR pathology of severe interstitial hemorrhage, inflammatory reaction, loss of glomerula and tubuli structure. Kidneys derived from mice transgenic for hDAF or hMCP were partially protected from both complement C3 deposition and tissue damage. The expression of both hDAF and hMCP in double transgenic mice significantly increases the protection from human complement-mediated damage., Conclusion: A novel model of in vivo perfusion with human plasma has been adopted to recreate the initial event of HAR. Our data show that this murine model could be very valuable to determine the effect of transgenic human molecules in protecting vascularized organs from human complement attack.

Purpose: Resiniferatoxin, a substance isolated from some species of euphorbia, a cactus-like plant, presents pharmacological effects similar to those of capsaicin. We studied the urodynamic effects of intravesical resiniferatoxin* in normal subjects and patients with unstable detrusor contraction to provide insight into the action mechanism of the molecule on sensory neurons and possible future pharmacological and clinical use., Materials and Methods: A total of 15 subjects with normal (8 patients) or unstable detrusor muscle (1 with detrusor instability and 6 with detrusor hyperreflexia) underwent urodynamic assessment during and after intravesical instillation of resiniferatoxin. Volume required to elicit the first desire to void, maximum bladder capacity and maximum bladder pressure were recorded during instillation of resiniferatoxin at a flow rate of 20 ml. per minute (normal subjects) or 15 minutes after instillation of 30 cc of a saline solution containing 10(-8) M. of resiniferatoxin and kept for 30 minutes in patients with unstable detrusor. The experiment was examined by the analysis of variance for repeated measures and post hoc comparisons were performed by Tukey-Kramer procedure. A p value <0.05 was accepted as significant., Results: Resiniferatoxin did not decrease the volume required to elicit the first desire to void and did not produce warm or burning sensations at the suprapubic/urethral level during infusion in subjects with normal detrusor function. In patients with bladder hyperactivity mean bladder capacity increased from 175.28 ml. plus or minus standard deviation 36.05 to 280.85 ml. plus or minus standard deviation 93.33 (p <0.01) immediately after treatment, and no significant modification of bladder pressure was recorded. Four weeks after treatment, bladder capacity remained increased in 2 patients but mean capacity did not increase significantly from 175.28 ml. plus or minus standard deviation 36.053 to 216.71 plus or minus standard deviation 86.91. The 2 patients with stable increase of bladder capacity reported significant clinical improvement of frequency, nocturia and incontinence 4 weeks later., Conclusions: Our results suggest that in humans there may be substantial differences in urodynamic effects between resiniferatoxin and capsaicin when the drugs are instilled into the bladder. Further studies, in vitro and in vivo, are necessary to define the pharmacological and clinical effects of resiniferatoxin. Because resiniferatoxin did not produce warm or burning sensations at the suprapubic/urethral level during infusion and seems to have rapid desensitization, it could be an interesting alternative to intravesical capsaicin in the treatment of select cases of bladder hyperactivity.

There have been only a few reports on the involvement of the urinary tract in patients with systemic sclerosis, a disease of the connective tissue characterized by thickening and fibrosis of the skin, abnormality of the small arteries, and involvement of the gastrointestinal tract, heart, lung and kidney. We report the urodynamic assessment and histological examination of 9 women with scleroderma. Three patients voided less than 100 ml. with a significant residual volume and 4 presented with detrusor areflexia during a filling cystometrogram. Histopathological examination in all patients with detrusor areflexia demonstrated the presence of arterial lesions and derangement of the capillary bed of the detrusor musculature. Our data provide evidence for the functional and histological involvement of the bladder in patients with systemic sclerosis.

We report a case of autotransplantation performed 21 years ago in a patient suffering from intractable loin pain. Long-term followup, the pathogenesis of pain in regard to renal innervation and the value of autotransplantation as a form of complete sensory denervation are discussed.

We report our first experience with the use of a small gastric patch for reconstruction of the renal pelvis. We performed left gastropyeloplasty based on the right gastroepiploic artery in 1 patient suffering from recurrent urinary tract infections and renal stones, and moderate renal failure. The use of a gastric patch for reconstruction of the renal pelvis prevented the recurrence of calculi and bacterial infections, and produced an improvement in renal function. We confirm the feasibility of the use of a small gastric patch in reconstruction of the renal pelvis and we argue that there are several possible ways to use stomach in upper urinary tract reconstruction.