Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Assessment of a program to encourage the multidisciplinary management of urinary disorders in multiple sclerosis.

AIMS: Urinary disorders (UD) secondary to multiple sclerosis (MS) are common and can be responsible for complications. Since 2004, we organized in our region their management through a neuro-urological activity and a care network that established and distributed an algorithm for screening and first line care. The objective was to assess the effects of this organization on the management of UD and its impact for patients. METHODS: Between January 2004 and December 2009, 328 patients were seen in neuro-urological consultation. The data of a group of 168 patients consulting during the deployment of our organization (before January 2007: group 1) were compared to those of 160 patients taken when the organization was well established (from January 2007: group 2). In parallel, the modification of the prescription rate of the first-line examination patients was evaluated. RESULTS: The two groups were significantly different concerning age, duration of MS, EDSS score (Group 1 vs. Group 2 respectively 51.6 ± 12.6 vs. 48 ± 11.8 years, P = 0.008; 19 ± 9.7 vs. 13.8 ± 10.5 years, P < 0.0001; 5.8 ±2.0 vs. 5.1 ± 2.1, P = 0.008). The occurrence of urinary complications in group 1 was more frequent than in group 2 (66.3% vs. 40%, P < 0.0001). The rate of first-line examinations rose from 1/16 patient seen in January 2006 to 9/12 patients in January 2008. CONCLUSION: The multidisciplinary management of UD in MS led to patients being cared for sooner in the evolution of MS, with fewer complications and to an improvement in the rate of prescription of first-line examinations. Neurourol. Urodynam. 36:706-709, 2017. © 2016 Wiley Periodicals, Inc.

Intradetrusor injections of onabotulinum toxin A (Botox®) 300 U or 200 U versus abobotulinum toxin A (Dysport®) 750 U in the management of neurogenic detrusor overactivity: A case control study.

AIMS: To compare the outcomes of the first intradetrusor injections of abobotulinum toxin 750 U and onabotulinum toxin 200 and 300 U in patients with neurogenic detrusor overactivity (NDO). METHODS: A retrospective case-control study was conducted including 211 NDO patients treated in three consecutives eras with onabotulinum toxin 300 U (2004-2006; 80 patients), abobotulinum toxin 750 U (2007-2011; 78 patients) or onabotulinum toxin 200 U (2011-2014; 53 patients). Urodynamic and clinical parameters were compared between groups. The primary endpoint was the rates of success defined as the combination of urgency, urinary incontinence, and detrusor overactivity resolution. RESULTS: When comparing abobotulinum toxin to onabotulinum toxin any doses (200 or 300 U; n = 133), success rates were similar (65.4% vs. 55.6%; P = 0.16). Patients treated with abobotulinum toxin 750 U had higher success rate (65.4% vs. 41.5%; P = 0.007) compared to those who received onabotulinum toxin 200 U. In contrast, there were similar success rates in abobotulinum toxin 750 U and onabotulinum toxin 300 U groups (65.4% vs. 65%; P = 0.91) but with a trend towards longer interval between the first and the second injection in the onabotulinum toxin 300 U group (12.4 vs. 9.3 months; P = 0.09). CONCLUSIONS: Intradetrusor injections of abobotulinum toxin 750 U for NDO provided better outcomes than injections of onabotulinum toxin 200 U. Success rates of abobotulinum toxin 750 U and onabotulinum toxin 300 U were similar but interval between injections tended to be longer with onabotulinum toxin 300 U. Neurourol. Urodynam. 36:734-739, 2017. © 2016 Wiley Periodicals, Inc.

Efficacy and safety of the first and repeated intradetrusor injections of abobotulinum toxin A 750 U for treating neurological detrusor overactivity.

PURPOSE: To assess clinical and urodynamic efficacy of the first and repeated intradetrusor injections of abobotulinum toxin A (Dysport(®), Ipsen(®), France) in patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergic treatment. METHODS: A single-center retrospective study was conducted in 81 consecutive patients who had never received any botulinum toxin intradetrusor injections. They were treated with at least one 750 U intradetrusor injection of abobotulinum toxin A. All patients performed clean intermittent self-catheterization (CIC) before injections. Success was defined as a combination of no incontinence episode, a number of catheterization <8 reported in a 3-day bladder diary and the lack of detrusor overactivity. RESULTS: Six weeks after the first injection, the success rate was 64.2 %. The proportion of continent patients was 80.2 %, the mean number of CIC per 24 h reduced (-3.55, p < 0.0001) and the mean catheterization volume increased (+237.3 ml, p < 0.0001). Regarding urodynamics, mean maximum cystometric capacity and mean volume at the first uninhibited contraction increased (+132.7 ml, p < 0.0001 and +180 ml, p < 0.0001, respectively) and mean maximum bladder pressure decreased significantly (-21.5 cm H2O, p < 0.0001). Mean reinjection number was 3.9 and mean interval between reinjection was 8.8 ± 3 months. The clinical efficacy rate after each reinjection (up to fourteen) was at least 86.7 %. Out of 55 patients who underwent repeated injections, secondary resistance was noted in 2 (3.6 %). CONCLUSION: The results of the present study are in favor of a long-term safety and efficacy of abobotulinum toxin A 750 U for NDO.

Laparoscopic nephrectomy for polycystic kidney: comparison of the transperitoneal and retroperitoneal approaches.

PURPOSE: To evaluate and compare perioperative outcomes in patients undergoing either transperitoneal (TP) or retroperitoneal (RP) laparoscopic nephrectomy for autosomal dominant polycystic kidney disease (ADPKD). METHODS: All patients with ADPKD who underwent unilateral laparoscopic nephrectomy between 2000 and 2012 in two academic departments were retrospectively included. The perioperative parameters were compared between the TP and RP groups. RESULTS: A total of 82 patients were included, 43 patients in the TP group and 39 in the RP group. The patients' characteristics were similar between TP set and RP set, except for the time from dialysis onset to nephrectomy (p = 0.02). Complication rates (25.6 vs 33.3 %, p = 0.44), transfusion rates (11.6 vs 20.5 %, p = 0.27) and conversion to open surgery (4.6 vs 7.7 %, p = 0.56) were similar between the TP and RP groups, respectively. Operative time was shorter for TP procedures (171.6 vs 210.5 min, p = 0.002), but there was no difference between the two approaches after 20 surgeries (p = 0.06). Patients in TP group had a shorter length of hospital stay (5.3 ± 1.9 vs 7.2 ± 2.5 days, p = 0.002). However, there was a trend towards shorter return of bowel function in the RP group (2.1 ± 0.9 vs 2.4 ± 0.8 days, p = 0.09). CONCLUSION: TP and RP laparoscopic nephrectomies provide good outcomes in patients with ADPKD. The choice of a TP route could decrease the length of hospital stay and the operative time during the beginning of the learning curve period.

Preliminary results of botulinum toxin A switch after first detrusor injection failure as a treatment of neurogenic detrusor overactivity.

AIMS: To assess the results of onabotulinum toxin detrusor injections when abobotulinum toxin detrusor injection failed. METHODS: Twenty-six patients, 15 women and 11 men, mean age 40.8 ± 12.7 years old, in whom a first injection of 750 U abobotulinum toxin in 20 sites failed in treating neurogenic detrusor overactivity, received onabotulinum toxin 300 U detrusor injections in 30 sites. Neurologic conditions were spinal cord injury in 14 cases, multiple sclerosis in nine, myelomeningocele in two and myelitis in one. Mean time between the two injections was 5.6 ± 1.4 months. Before and 6 weeks after each injection, patients carried out a 3-day bladder diary and had urodynamics. The success was defined as the combination of a clean intermittent self-catheterization number under 8 per 24 hr, urgency, urinary incontinence and detrusor overactivity relief. RESULTS: Out of 26 patients, the second injection was successful in 15 (57.7%). While the first injection of 750 U abobotulinum toxin had no impact at all, after 300 U onabotulinum toxin injection, the number of clean intermittent self-catheterization decreased significantly (11.3 ± 2.1 vs. 6.4 ± 1.9, P = 0.01), 17/26 (65.4%) patients achieved continence, urgency was relieved in 18/26 (69.2%) and detrusor overactivity in 15/26 (57.7%). CONCLUSIONS: In case of failure after a first detrusor injection of abobotulinum toxin, switching for onabotulinum toxin is efficient. Further investigations should be performed to assess whether the replacement of onabotulinum toxin by abobotulinum toxin provides the same results.

Prostate cancer incidence on cystoprostatectomy specimens is directly linked to age: results from a multicentre study.

OBJECTIVE: To assess the incidence and age-related histopathological characteristics of incidentally diagnosed prostate cancer from specimens obtained via radical cystoprostatectomy (RCP) for muscle-invasive bladder cancer. PATIENTS AND METHODS: A retrospective review of the histopathological features of 2424 male patients who underwent a RCP for bladder cancer was done at eight centres between January 1996 and June 2012. No patient had preoperative suspicion of prostate cancer. Statistical analyses were performed in different age-related groups. RESULTS: Overall, prostate cancer was diagnosed in 518 men (21.4%). Incidences varied significantly according to age (5.2% in those aged <50 years to 30.5% in those aged >75 years, P < 0.001). Most of the prostate cancers were considered as 'non-aggressive', that is to say organ-confined (≤pT2) and well-differentiated (Gleason score <7). Tumour-Node-Metastasis (TNM) stage and proportion with a Gleason score of ≥7 were significantly greater in older patients (P < 0.001). Apart from age, there were no preoperative predictive factors for 'non-aggressive' prostate-cancer status. At the end of the follow-up, only nine patients (1.7%) had biochemical recurrence of prostate cancer, and no preoperative predictive factors were identified. CONCLUSION: The rate of incidentally diagnosed prostate cancer from RCP specimens is ≈20%, most of them being organ-confined and well-differentiated. The probability of having a 'non-aggressive' prostate cancer decreases in older men.

Technical solutions to improve the management of non-muscle-invasive transitional cell carcinoma: summary of a European Association of Urology Section for Uro-Technology (ESUT) and Section for Uro-Oncology (ESOU) expert meeting and current and future perspectives.

The aim of the present review was to compare state-of-the-art care and future perspectives for the detection and treatment of non-muscle-invasive transitional cell carcinoma (TCC) of the bladder. We provide a summary of the third expert meeting on 'Optimising the management of non-muscle-invasive bladder cancer, organized by the European Association of Urology Section for Uro-Technology (ESUT) in collaboration with the Section for Uro-Oncology (ESOU), including a systematic literature review. The article includes a detailed discussion on the current and future perspectives for TCC, including photodynamic diagnosis, optical coherence tomography, narrow band imaging, the Storz Professional Image Enhancement system, magnification and high definition techniques. We also provide a detailed discussion of future surgical treatment options, including en bloc resection and tumour enucleation. Intensive research has been conducted to improve tumour detection and there are promising future perspectives, that require proven clinical efficacy. En bloc resection of bladder tumours may be advantageous, but is currently considered to be experimental.

Development of a standardised training curriculum for robotic surgery: a consensus statement from an international multidisciplinary group of experts.

OBJECTIVES: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. MATERIALS AND METHODS: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. RESULTS: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement κ 0.89) and they included: need for a training curriculum (inter-rater agreement κ 0.85); identification of learning needs (κ 0.83); development of the curriculum contents (κ 0.81); an overview of available curricula (κ 0.79); settings for robotic surgery training ((κ 0.89); assessment and training of trainers (κ 0.92); requirements for certification and patient safety (κ 0.83); and need for a universally standardised curriculum (κ 0.78). A training curriculum was proposed based on the above discussions. CONCLUSION: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.

Differences in practice patterns between urologists and radiation oncologists in the management of localized prostate cancer: a cross-sectional survey.

INTRODUCTION: Through a cross-sectional survey, we tried to assess whether practices of urologists and radiation oncologists are uniform when faced with similar clinical situations. MATERIALS AND METHODS: A self-administered questionnaire was mailed to all French urologists and radiation oncologists. Respondents were asked about their practices through 11 case scenarios. The scenarios cover most of localized prostate cancer situations and were gradually organized depending on prostate cancer progression risk and the age of the patient. The eight first scenarios address the situation of treatment-naive patients, and the last cases were about the management of patients after radical prostatectomy. Physicians were asked to choose a treatment modality for each case. The responses were first stratified according to the intention to treat: either curative-intent treatment or palliative. The curative-treatment modality chosen were afterward assessed. The responses to clinical scenarios were compared between the two specialties. RESULTS: Concerning the intention to treat, practice patterns were overall consistent except in one case. Indeed, a higher rate of radiation oncologists prefer curative-intent treatment for intermediate-risk prostate cancer in aged patients: 57.4 versus 14.6 % (p < 0.001). Each medical specialist prefers the treatment that he himself delivers (p < 0.005). For intermediate-risk prostate cancer in 65-year-old patient: 96.5 % of urologists chose radical prostatectomy versus 37.7 % of radiation oncologists (p < 0.001). Fewer urologists (almost 14 %) compared to radiation oncologists (47.5 %) would prescribe adjuvant treatment after radical prostatectomy for T3a R0 prostate cancer with post-operative PSA undetectable (p < 0.001). CONCLUSION: Significant differences were found in therapeutic approach between the two main specialties that deal with localized prostate cancer.

Urinary complications and risk factors in symptomatic multiple sclerosis patients. Study of a cohort of 328 patients.

AIMS: Lower urinary tract dysfunctions (LUTD) are very common in Multiple Sclerosis (MS), have a significant social impact, while the organic impact is discussed. We studied urinary complications and their risk factors in our cohort of MS patients, in order to improve the management of LUTD in MS. METHODS: Between 2004 and 2009, all patients affected by MS and managed for LUTD were included in a retrospective study. We studied the epidemiological data (age, gender), the clinical data (duration of MS, EDSS score, progression of MS) and the paraclinical data (urinary creatinine clearance, urine culture, urinary tract ultrasonography and in some cases urodynamic assessment and cystography). We then identified the urinary complications and their risk factors. RESULTS: Three hundred twenty eight patients, mean age 49.9 ± 12.3 years, with a MS for 14.3 ± 10 years on average and with a median EDSS score equal to 6 (1-9), were managed for LUTD. One hundred seventy eight (54%) patients developed one or more urinary complications. We identified duration of MS greater than 8.5 years and an EDSS above 7 as risk factors. CONCLUSION: Urinary complications are common in symptomatic MS, these results imply screening and specialized care to limit the impact on the quality of life but also to prevent urinary complications.

Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

OBJECTIVES: To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. METHODS: The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. RESULTS: A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). CONCLUSION: After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results.

Sphingosine Kinase 1 urothelial expression is increased in patients with neurogenic detrusor overactivity.

UNLABELLED: To evaluate the expression of sphingosine kinase 1 (SPK1) in the bladder wall in patients with neurogenic lower urinary tract dysfunction and its association with clinical, urodynamic and pathological features. MATERIALS AND METHODS: The expression of SPK1 was studied in bladder wall specimens obtained from cystectomy using immunohistochemistry in ten patients with spinal cord injury (n=8) or multiple sclerosis (n=2) with urodynamically proven neuropathic bladder dysfunction, and in controls (n=5). Inflammation and fibrosis were analysed with histological criteria and SPK1 expression was determined by individual immunohistochemical staining. RESULTS: Significant increased SPK1 urothelial immunoreactivity was shown in patients compared to control group (p=0.03). By contrast, SPK1 immunoreactivity in patients was significantly decreased in the sub-urothelium, muscles and nerves, p=0.02; 0.01 and 0.003, respectively. Patients with neurogenic detrusor overactivity (NDO) had higher SPK1 urothelium expression than those without any DO (p=0.04). CONCLUSIONS: SPK1 is expressed in the human bladder wall, specifically the urothelium, in bladder specimens from patients with NDO. The role of SPK1 in the pathophysiology of NDO needs further elucidation.

Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.

PURPOSE: The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. METHODS: We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. RESULTS: Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. CONCLUSIONS: The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.

External validation of the Briganti nomogram to estimate the probability of specimen-confined disease in patients with high-risk prostate cancer.

OBJECTIVE: To establish an external validation of the updated nomogram from Briganti et al., which provides estimates of the probability of specimen-confined disease using the variables age, prostate-specific antigen (PSA), clinical stage and biopsy Gleason score in preoperatively defined high-risk prostate cancer (PCa). PATIENTS AND METHODS: The study included 523 patients with high-risk PCa, as defined by d'Amico classification, undergoing radical prostatectomy (RP) and bilateral lymph node dissection in one of two academic centres between 1990 and 2013. Specimen-confined disease was defined as pT2-pT3a node-negative PCa with negative surgical margins. The receiver-operator characteristic (ROC) curve was obtained to quantify the overall accuracy (area under the curve [AUC]) of the model in predicting specimen-confined disease. A calibration curve was then constructed to illustrate the relationship between the risk estimates obtained by the model (x-axis) and the observed proportion of specimen-confined disease (y-axis). The Kaplan-Meier method was used to assess biochemical recurrence (BCR)-free survival. RESULTS: Patients' median age and PSA level were 64 years and 21 ng/mL, respectively. The definition of high-risk PCa was based on PSA level only in 38.3%, a biopsy Gleason score >7 in 34.5%, a clinical stage >T2b in 6.9%, or a combination of these two or three factors in 20.3% of patients. Positive surgical margins were observed in 43.6%, with a rate of 14.8% in pT2 cancers and lymph node metastasis in 12.1% of patients. pT stage was pT0 in 0.9%, pT2 in 28.9%, pT3a in 37.5% and pT3b-4 in 32.7% of patients. Overall, 44.4% of patients (N = 232) had specimen-confined disease. PSA and cT stage were independently predictive of specimen-confined disease. The median (range) 2-, 5-, and 8-year BCR-free survival rates were significantly higher in specimen-confined disease as compared with non-specimen-confined disease: 80.87 (73.67-86.29) vs 37.55 (30.64-44.44)%, 63.53 (52.37-72.74) vs 26.93 (19.97-34.36)% and 55.08 (41.49-66.74) vs 19.52 (12.50-27.70)%, respectively (P < 0.001). The ROC curve analysis showed relevant accuracy of the model (AUC 0.6470, 95% CI 0.60-0.69) although the calibration plot suggested that, for risks ranging from 0.3 to 0.5, the odds of extracapsular extension were underestimated. CONCLUSIONS: This external validation of the Briganti nomogram shows relevant accuracy, although the relative imprecision for intermediate risk may limit its clinical relevance. Our follow-up findings confirm the large proportion of specimen-confined PCa with good oncological outcomes in this heterogeneous subgroup of patients with high-risk PCa.

Modulation of nerve-evoked contractions by ß3-adrenoceptor agonism in human and rat isolated urinary bladder.

Activation of ß3-adrenoceptors has been shown to have a direct relaxant effect on urinary bladder smooth muscle from both rats and humans, however there are very few studies investigating the effects of ß3-adrenoceptor agonists on nerve-evoked bladder contractions. Therefore in the current study, the role of ß3-adrenoceptors in modulating efferent neurotransmission was evaluated. The effects of ß3-adrenoceptor agonism on neurogenic contractions induced by electrical field stimulation (EFS) were compared with effects on contractions induced by exogenous acetylcholine (Ach) and αß-methylene adenosine triphosphate (αß-meATP) in order to determine the site of action. Isoproterenol inhibited EFS-induced neurogenic contractions of human bladder (pD2=6.79; Emax=65%). The effect of isoproterenol was selectively inhibited by the ß3-adrenoceptor antagonist L-748,337 (pKB=7.34). Contractions induced by exogenous Ach (0.5-1µM) were inhibited 25% by isoproterenol (3µM) while contractions to 10Hz in the same strip were inhibited 67%. The selective ß3-adrenoceptor agonist CL-316,243 inhibited EFS-induced neurogenic contractions of rat bladder (pD2=7.83; Emax=65%). The effects of CL-316,243 were inhibited in a concentration dependent manner by L-748,337 (pA2=6.42). Contractions induced by exogenous Ach and αß-meATP were significantly inhibited by CL-316,243, 29% and 40%, respectively. These results demonstrate that the activation of ß3-adrenoceptors inhibits neurogenic contractions of both rat and human urinary bladder. Contractions induced by exogenously applied parasympathetic neurotransmitters are also inhibited by ß3-agonism however the effect is clearly less than on neurogenic contractions (particularly in human), suggesting that in addition to a direct effect on smooth muscle, activation of prejunctional ß3-adrenoceptors may inhibit neurotransmitter release.

Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO).

Murine unilateral ureteral obstruction (UUO), a major model of progressive kidney disease, causes loss of proximal tubular mass and formation of atubular glomeruli. Adult C57BL/6 mice underwent a sham operation or reversible UUO under anesthesia. In group 1, kidneys were harvested after 7 days. In group 2, the obstruction was released after 7 days, and a physiological study of both kidneys was performed 30 days later. Renal blood flow (RBF), glomerular filtration rate (GFR), urine protein, and albumin excretion were measured after ligation of either the left or right ureter. Glomerular volume (periodic acid-Schiff), glomerulotubular integrity and proximal tubular mass (Lotus tetragonolobus lectin), and interstitial collagen (Sirius red) were measured by histomorphometry. Obstructed kidney weight was reduced by 15% at 7 days but was not different from sham after a 30-day recovery. Glomerular volume and proximal tubular area of the obstructed kidney were reduced by 55% at 7 days, but normalized after 30 days. Interstitial collagen deposition increased 2.4-fold after 7 days of UUO and normalized after release. However, GFR and RBF were reduced by 40% and urine albumin/protein ratio was increased 2.8-fold 30 days after release of UUO. This was associated with a 50% reduction in glomerulotubular integrity despite a 30-day recovery (P < 0.05 for all data). We conclude that release of 7-day UUO can arrest progression but does not restore normal function of the postobstructed kidney. Although the remaining intact nephrons have hypertrophied, glomerular injury is revealed by albuminuria. These results suggest that glomerulotubular injury should become the primary target of slowing progressive kidney disease.

Predictive factors of complications after robot-assisted laparoscopic partial nephrectomy: a retrospective multicentre study.

OBJECTIVE: To analyse the predictive factors of complications after robot-assisted laparoscopic partial nephrectomy (RALPN). MATERIALS AND METHODS: Data from six French institutions on 240 patients who underwent RALPN between 2009 and 2011 were retrospectively reviewed. Clinical (age, body mass index, American Society of Anesthesiologists and Charlson comorbidity index scores, anticoagulant treatment), tumoral (size, R.E.N.A.L nephrometry score) and operative (surgeon experience, blood loss, opening of the collecting system, operating time) variables were considered. Univariate and multivariate regression models were used to assess the impact of these variables on the occurrence of global and major postoperative complications, classified according to the Clavien system. RESULTS: The median (range) patient age was 61 (26-83) years. Tumours were of low complexity in 62% of cases. Median (range) operating time, blood loss and warm ischaemia time were 161 (45-425) min, 100 (0-2500) mL and 20 (0-59) min, respectively. Postoperative complications occurred in 79 (33%) patients. Complications were ≥ grade III in 25 (10%) patients and were mostly haemorrhagic. In multivariate analysis, surgeon's experience (hazard ratio [HR]: 2.14 [1.07-4.27], P = 0.03) and blood loss (HR: 1.002 [1.001-1.003], P < 0.001) were independent predictors of overall complications. When considering major complications, opening of the collecting system was the only factor that was significant (OR: 2.99 [1.2-7.26], P = 0.02). Nephrometry R.E.N.A.L. score was not associated with postoperative complications. CONCLUSION: In our experience, RALPN is associated with a 30% risk of postoperative complications; surgeon's experience, blood loss and opening of the collecting system were the three predictors of postoperative complications.

A prospective comparison of surgical and pathological outcomes obtained after robot-assisted or pure laparoscopic partial nephrectomy in moderate to complex renal tumours: results from a French multicentre collaborative study.

OBJECTIVE: To prospectively compare the surgical and pathological outcomes obtained with robot-assisted laparoscopic partial nephrectomy (RAPN) or laparoscopic PN (LPN) for renal cell carcinoma in a multicentre cohort. PATIENTS AND METHODS: Between 2007 and 2011, 265 nephron-sparing surgeries were performed at six French urology departments. The patients underwent either RAPN (n = 220) or LPN (n = 45) procedures. The operative data included operative duration, warm ischaemia time (WIT) and estimated blood loss (EBL). The postoperative outcomes included length of stay (LOS), creatinine variation (Modification of Diet in Renal Disease group), Clavien complications and pathological results. The complexity of the renal tumour was classified using the R.E.N.A.L. nephrometry scoring system. Student's t-test and chi-squared tests were used to compare variables. RESULTS: The median follow-ups for the RAPN and LPN groups were 7 and 18 months, respectively (P < 0.001). Age and American Society of Anesthesiology score were significantly higher in the LPN group (P = 0.02 and P = 0.004, respectively). These variables were lower in the RAPN group: WIT [mean (sd) 20.4 (9.7) vs 24.3 (15.2) min; P = 0.03], operative duration [mean (sd) 168.1 (55.5) vs 199.7 (51.2) min; P < 0.001], operating room occupation time [mean (sd) 248.3 (66.7) vs 278.2 (71.3) min; P = 0.008], EBL [mean (sd) 244.8 (365.4) vs 268.3 (244.9) mL; P = 0.01], use of haemostatic agents [used in 78% of RAPNs and 100% of LPNs; P < 0.001] and LOS [mean (sd) 5.5 (4.3) vs 6.8 (3.2) days; P = 0.05). There were no significant differences between pre- and postoperative creatinine levels, pathology report or complication rates between the groups. The main limitation was due to the study's non-randomised design. CONCLUSION: RAPN is not inferior to pure LPN for perioperative outcomes (i.e. EBL, operative duration, WIT, LOS). Only a randomised study with a longer follow-up can now provide further insight into oncological outcomes.

Vaginal lubrication after cervicovaginal stimulation is facilitated by phosphodiesterase type 5 inhibition in ovariectomized mice.

INTRODUCTION: Nitric oxide synthases (NOSs) and estrogen receptors are expressed in the vagina. AIM: We aimed to assess the impact of sildenafil on vaginal lubrication according to the hormonal status and to determine the role of the neuronal isoform of NOS (nNOS). METHODS: Four-week-old C57/BL6 female mice were sham operated or ovariectomized. At 10 weeks of age, they were injected intraperitoneally by any combination of sildenafil, 7-nitroindazole (7-NI)--a potent selective nNOS inhibitor--or the corresponding vehicles. Vaginal lubrication was induced in a physiological manner by cervical vaginal probing and quantified depending on the hormonal and pharmacological conditions. The animals were then sacrificed for vaginal histomorphometry. MAIN OUTCOME MEASURES: The main outcome measure is the quantification of vaginal transudate after cervicovaginal stimulation and vaginal histomorphometry. RESULTS: Sildenafil increased cervicovaginal probing-induced vaginal lubrication in ovariectomized and sham-operated animals. Ovariectomized mice exhibited decreased vaginal lubrication as compared with sham-operated mice. When taking into account the presence of severe vaginal atrophy, a threefold increase in transudate per gram of vagina wet weight was revealed in ovariectomized animals. Castration markedly reduced the thickness of the vaginal wall. nNOS inhibition by 7-NI had no impact on vaginal lubrication. CONCLUSIONS: Irrespective of the hormonal status, sildenafil increased vaginal lubrication. The vaginal effect of sildenafil was independent of the nNOS pathway and more pronounced in ovariectomized animals.