Malignancy after Augmentation Enterocystoplasty: A Nationwide Study of Natural History, Prognosis and Oncogene Panel Analysis.

PURPOSE: We report the natural history and prognosis of tumors after augmentation enterocystoplasty, with a molecular analysis using an oncogene panel to search for potential targeted therapies. MATERIALS AND METHODS: This multicenter, nationwide, retrospective study included 16 patients. A panel of 21 clinically relevant oncogenes was tested on archival tumor specimens using next-generation sequencing. Survival rate was the main clinical outcome and sequences were compared to the reference genome for the genetic outcome. RESULTS: Augmentation enterocystoplasties were performed mainly for congenital neurogenic bladder and bladder exstrophy at a median patient age of 17 years (range 4 months to 45 years). Most of the malignancies were diagnosed because of clinical manifestations, with a median latency period of 20 years. Adenocarcinomas were mainly found after gastrocystoplasty, whereas urothelial cell carcinomas were typically found after colocystoplasty. Of the 16 patients 13 were diagnosed at an advanced stage of the disease (positive lymph nodes in 7, distant metastases in 6). The overall 1-year survival rate was 56%. Only 3 patients remained disease-free at a median followup of 70 months. Of the 9 tumors with analyzable DNA 4 were wild-type and 5 harbored missense mutations (KIT-p.Pro573Ser, PDGFRA-p.Glu587Lys, KRAS-p.Gly12Asp, ERBB4p.Arg484Lys, CTNNB1-p.Ser37Phe and p.Ser47Asn). CONCLUSIONS: Malignancy after augmentation enterocystoplasty is diagnosed late with frequent metastases and a very low 1-year survival rate. More than half the tested samples harbored missense mutations in oncogenes accessible to targeted therapies. An international collaboration to enlarge the genetic panel analysis of these tumors may offer new therapeutic hope to patients.

[Cost comparison of open and robot-assisted partial nephrectomy in treatment of renal tumor]. / Comparaison médico-économique de la laparoscopie robot-assistée et de la lombotomie pour la réalisation de néphrectomies partielles pour cancer du rein.

INTRODUCTION: Robot-assisted partial nephrectomy rapidly took on among urologists, even though studies showing its superiority over other techniques are still scarce and its costs hard to evaluate, especially in the French medical system. OBJECTIVE: To evaluate the cost overrun of robot-assisted partial nephrectomy compared to that of open partial nephrectomy. EQUIPMENT AND METHODS: From January 2010 to December 2013, 77 patients underwent a partial nephrectomy, 46 of which by robot-assisted laparoscopy and the remaining 31 by lombotomy. The two groups were similar in composition. Economic data regarding the staff, the consumables and the premises involved have been analyzed. RESULTS: Costs are significantly higher in the NPR group (9253.21 euros vs. 7448.42 euros) due to higher consumable expenses as well as the costs pertaining to the amortization and maintenance of the robot. Yet, that difference tends to diminish as the duration of the experiment increases. No significant difference was found in warm ischemia times, operation duration and renal function a month after the operation. On the other hand, patients from the NPR group spent a significantly smaller amount of time in recovery room (159 minutes vs. 205 minutes, P=0.004), presented fewer complications and were discharged faster (6.1 days vs. 8.1 days, P=0.04). CONCLUSIONS: To be profitable for the hospital in the French GHS system, robot-assisted partial nephrectomy must take place in a complex where at least 300 robot-assisted interventions are performed annually, in the framework of a hospitalization lasting four days or less, the use of a single needle holder and no systematic use of a haemostatic agent. LEVEL OF EVIDENCE: 4.

[Efficacy of periurethral injections of polyacrylamide hydrogel (Bulkamid(®)) and quality of life of patients with urinary incontinence due to sphincter deficiency (IUE-IS)]. / Efficacité des injections péri-urétrales de polyacrylamide hydrogel (Bulkamid(®)) et qualité de vie de patientes souffrant d'incontinence urinaire d'effort par insuffisance sphinctérienne (IUE-IS).

INTRODUCTION: This study was carried out to evaluate the efficacy of periurethral injection of polyacrylamide hydrogel (PAHG, Bulkamid(®), Ethicon) for the treatment of female stress urinary incontinence (SUI). METHODS: Single-center prospective study: periurethral injection of Bulkamid(®) was performed in 80 patients with severe urinary incontinence between June 2010 and October 2011. The evaluation of the impact on quality of life was carried out using the Patient Global Impression of Severity (PGI-S), the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and Patient Global Impression of Improvement (PGI-I) before and after treatment. RESULTS: With a mean follow-up of 18.6 ± 5.3 months, 60% of patients had improved. For 30/74 (40%) there was no improvement and no patient had worsening of PGI-I after injection. Before surgery, 55.4% of patients considered their condition as severe (PGI-S). After injecting 21/74 (28%) and 11/74 (15%) considered it normal and severe (zero leakage). The ICIQ -SF score increased from 17 ± 2.84 before injection to 13 ± 5.52 after surgery, with a significant 30% decrease (P<0.00001). The reinjection rate was 29%. The complication rate was 16% (17/108): 11 cases of transient postoperative retention, 2 cases of cystitis, dysuria four episodes. No abscess or infection at the injection site, no specific complication to the product used. CONCLUSION: With an (PGI-I) improvement rate of 60 and 15% of patients without leakage (PGI-S/ICIQ), periurethral injection of Bulkamid(®) is an effective and safe treatment option for women with a severe urinary incontinence especially in therapeutic failure. LEVEL OF PROOF: 4.

[Percutaneous ethanol sclerotherapy of symptomatic renal cysts: results after 4 years]. / Sclérothérapie percutanée à l'éthanol des kystes rénaux symptomatiques : résultats à 4 ans.

OBJECTIVES: The main objective was to investigate the long-term clinical and radiological effectiveness/safety of ethanol sclerotherapy for treating simple kidney cysts.The secondary objective was to evaluate the effectiveness of a second alcohol treatment after 24 hours of drainage for large cysts. PATIENTS: A retrospective study was carried out from January 2005 to March 2012 on 24 patients with simple kidney cysts treated by percutaneous ethanol sclerotherapy during ambulatory surgery. Therapeutic success was defined as symptom resolution and regression of cyst size by > 60%. Incomplete regression was defined as a decrease between 50 and 60% and a recurrence as a residual size > 50%. Drainage was left in place for 24 hours for patients with a cyst > 900 cm(3) and a second alcohol treatment was performed the next day. All patients were invited for ultrasound follow up as part of the study. RESULTS: Treatment success was observed in 91.6% of patients. Two patients had incomplete regression. No recurrence was observed. No intraoperative or postoperative complications were found. CONCLUSION: Sclerotherapy for simple kidney cysts is a safe and effective procedure that can be performed under local anesthesia and an outpatient setting in most cases. Systematic drainage for 24 hours followed by a second alcohol treatment may reduce the risk of recurrence for large cysts.

[Consequences of coelioscopic sacrocolopoxy on the sexuality of the couple]. / Impact des cures de prolapsus pelviens par promontofixation laparoscopique sur la sexualité du couple.

AIM: To assess the impact on the sexuality of the couple of pelvic organ prolapse repair with coelioscopic sacrocolopoxy. MATERIAL: Pilot, prospective, monocentre study conducted in Nîmes university hospital. Consecutive patients undergoing coelioscopic sacrocolpopexy and their partner were invited to participate. Women attended a pre-surgical visit and a 6-month post-surgery visit where pelvic organ prolapse status was clinically assessed. In the same time, they and their partner filled general quality of life and specific sexual quality of life questionnaires (questionnaires PISQ12, PFDI-20 in women, medical history, IIEF, modified PISQ12 questionnaires in men). RESULTS: From May to December 2010, 25 couples were assessed. Anatomical success rates (POPQ<2) in the middle, anterior and posterior compartments were respectively of 100%, 95.4% and 66.7%. After surgery, 65.2% of pairs (n=15) reported an at least hebdomadal frequency of sexual intercourse, as compared with 54.2% (n=13) of pairs before surgery (P<0.001). Two cases of decrease of sexual intercourses frequency were reported and appeared partner-related. There was an overall non-significant improvement in sexual quality of life in men and women. General pelvic organ distress, urinary incontinence and specific pelvic organ prolapse distresses were significantly improved after surgery. CONCLUSION: Coelioscopic sacrocolpopexy does not impair couple's sexuality, assessed as sexual intercourses frequency and could even improve it. Partner's assessment can bring important information with respect to the interpretation of functional sexual results of surgery.

[Treatment of women urinary incontinence by artificial urinary sphincter: efficacy, complications and survival]. / Traitement de l'incontinence urinaire par sphincters urinaires artificiels chez la femme : efficacité, complications et survie.

OBJECTIVE: To analyze long-term results and mechanical survival of the artificial urinary sphincter (AUS) AMS 800™ (American Medical Systems, Minnetonka, MN, USA) in women with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). PATIENTS AND METHODS: Data were collected prospectively from women treated for SUI at one university hospital between 1987 and 2007. Inclusion criteria was SUI with severe ISD defined by low urodynamic closure pressure and negative continence tests. Endpoints were survival, complications and continence. RESULTS: A total of 376 AUS were implanted in 344 patients with a median age of 57 years (18-93 years). The median follow-up was 9 years (3-20 years). The 3, 5, and 10 years global device survival were 92, 88.6, and 69.2% respectively. The mean mechanical survival was 176 months (14.7 years). The two main risk factors for decreased AUS survival were the number of previous incontinence surgeries and the presence of neurogenic bladder. The continence rates assessed as full (no leakage) in 85.64% patients, social (some drops but no pad) in 8.78% and incontinence (1 pad or more) in 5.58%. CONCLUSIONS: The study has shown that in patients with ISD, the AUS represents an effective process, durable with an acceptable rate of complication.

Robot-assisted laparoscopic nephron sparing surgery for tumors over 4 cm: operative results and preliminary oncologic outcomes from a multicentre French study.

OBJECTIVE: To assess operative and pathological results obtained after robot-assisted partial nephrectomy (RAPN) in renal masses over 4 cm. PATIENTS AND METHODS: Between 2007 and 2011, 220 robotic nephron-sparing surgeries (NSS) were performed at six French urology departments. Data were prospectively collected: age, BMI, pre and post-operative eGFR (MDRD), operative time (OT), warm ischemia time (WIT), estimated blood loss (EBL), length of hospital stay (LOS), Clavien complications, pathological results and oncologic outcome. Tumor complexity was assessed according to the RENAL nephrometry score. RESULTS: Overall, 54 tumors were included. Median follow up was 26 months. Median age at surgery was 62 years. Median RENAL nephrometry score was 7 (4-10). Median WIT was 23 min (10-59). Median OT and EBL were 180 min (110-425) and 100 cc (0-2500). Blood transfusion occurred in 7 cases (13%). Median tumor size was 45 mm (40-70). Three patients had positive surgical margins. Median LOS was 5 days (2-28). Nine patients presented post-operative complications of which 1/3 were considered as major (Clavien IIIb). Median pre-operative and post-operative eGFR was 88 (36-136) and 75 ml/min (33-122) (p = 0.01), respectively. Two patients developed subsequent metastasis. The 2-year progression free survival (PFS) rate was 90.5%. CONCLUSION: Our results confirm that RAPN is a useful and acceptable approach for renal masses greater than 4 cm in size. When technically possible, NSS provides promising short-term cancer-specific survival rates with acceptable morbidity. Tumor size is not sufficiently discriminant enough and RENAL nephrometry score should increasingly used to describe tumor complexity.

[Functional MRI by general radiologists in prediction of side-specific extracapsular extension after radical prostatectomy: what value in daily practice?]. / IRM fonctionnelle par des radiologues généralistes, dans la prédiction de l'extension extracapsulaire lobe spécifique après prostatectomie radicale : quelle valeur en pratique quotidienne ?

OBJECTIVE: To evaluate the performance of functional MRI (FMRI) performed by general radiologists (GR) in detection of side-specific extracapsular extension (SSECE) prostate cancer (PCa). METHODS: We retrospectively analyzed 79 patients who underwent FMRI with pelvic phased array coil before radical prostatectomy (RP) performed at University Hospital (UH) of Nîmes. Twelve GR (including three from UH) interpreted the images during their daily practice. FMRI results were dichotomized as positive or negative and confronted to pathological reports for SSECE and side-specific seminal vesicle invasion (SSSVI), with calculation of diagnostic values. The influence of interval between biopsy and FMRI, diffusion-weighted sequence (DWS) and intensity of FMRI, on the diagnostic performance were assessed by Fisher's exact test. RESULTS: A SSECE and a SSSVI were observed at FMRI and pathology respectively on 14 (8.8%) and 38 (24.1%) prostate lobes, and on six (3.8%) and seven (4.4%) prostate lobes. The sensitivity, specificity, positive and negative predictive values of FMRI for SSECE were respectively 24%, 96%, 64% and 80%; and for SSSVI were 14%, 97%, 17% and 96% respectively. The time between biopsy and FMRI, intensity of FMRI and DWS, did not influence the sensitivity and specificity of fMRI at Fisher test. CONCLUSION: This study found that preoperative prostate FMRI performed by GR has good specificity but poor sensitivity in predicting SSECE on pathological reports.

[Interest of flexible videocystoscopy in blue light (+Hexvix(®)) in consultation for the diagnosis of vesical tumor]. / Intérêt de la vidéocystoscopie souple en lumière bleue (+Hexvix(®)) en consultation pour le diagnostic des tumeurs de vessie.

OBJECTIVES: Estimate the feasibility and the results of the realization in consultation of a flexible videocystoscopy in blue light preceded by an instillation of Hexvix(®) (GE Healthcare) for the initial diagnosis or the surveillance of vesicals tumors (VT). The objective of this study was to compare the number of hurts seen in white light and in blue light, and to estimate in which percentage of case the use of the Hexvix(®) in consultation modified the care. PATIENTS AND METHODS: Thirty consecutive patients (26 men and four women) were estimated prospectively by vesical videofibroscopy in blue light (Wolf's PD videofibroscope) realized 1 hour after an endovesical instillation of Hexvix(®). All the examinations were realized in external consultation under local anesthetic by xylocaine gel: 23 (76.6%) patients within the framework of a surveillance of VT and seven (23.4%) for the diagnosis of a hematuria with normal echography. When a suspect hurt or a VT was discovered, the patients benefited from an endoscopic resection under anesthesia with new cystoscopy in blue light. RESULTS: Suspect hurts were revealed in 10 out of 30 patients, five in white and blue light, five in blue light only. Among the five only visible hurts in blue light, three were urothelial tumors (any pTa of bottom-rank, less of 5 mm) and two non-specific hurts. No CIS's hurt was revealed during this study. The fibroscopy in blue light allowed to diagnose invisible hurts in white light in three patients (10%) and has modified the care of five patients (16.7%). The duration of the cystoscopy was on average of 9.5 minutes. The tolerance of the examination was good and no complication arose. CONCLUSION: The use of the flexible videocystoscopy in blue light +Hexvix(®) has allowed to improve the rate of detection of VT. Except CIS's hurts, this improvement was bound to the diagnosis of little aggressive small-sized VT. The indications must be specified by studies of bigger scale and a medical economic evaluation.

[A technique of continent vesicostomy with ileocystoplasty: study of 32 patients]. / Une technique modifiée de cystostomie continente avec iléocystoplastie d'agrandissement : à propos d'une série de 32 patients.

OBJECTIVES: To evaluate the functional outcomes and quality of life of adult's disabled motor with neurogenic bladders, who had undergone a continent catheterizable vesicostomy with ileocystoplasty permitting a systematic implantation of the stoma at the umbilicus without closure of the bladder neck. METHODS: Between 2004 and 2006, 32 adults with neurogenic bladder who underwent Mitrofanoff continent catheterizable vesicostomy with ileocystoplasty were evaluated with the "Qualiveen" and a local satisfaction questionnaire. The median age was 42.2 years. The neurological diagnoses were: spinal cord injury (26), spina bifida (two) and multiple sclerosis (four). The cystostomies were conducted with appendix (17) and the ileum according Monti's technique (15). The stomas were conducted in 29 cases at the umbilicus. RESULTS: The 31 patients were followed up for a mean of 21.6 months. The continence rate was 86%. The satisfaction with functional result and aesthetic of the stoma was of 88% and 92%. Capacity to self catheterize increased from 64% to 88%. Thirty-three percent of stoma stenosis was noted and 36% of patients underwent a reintervention including 25% for stenosis. CONCLUSION: The results of this study have demonstrated that the ileocystoplasty with umbilical continent vesicostomy fullfill with treatment objective's of patients with neurogenic bladder: restoration of continence and improved quality of life by granting them social life.

Selective high-affinity transport of aspartate by a Drosophila homologue of the excitatory amino-acid transporters.

Excitatory amino-acid transporters (EAATs) are structurally related plasma membrane proteins that mediate the high-affinity uptake of the acidic amino acids glutamate and aspartate released at excitatory synapses, and maintain the extracellular concentrations of these neurotransmitters below excitotoxic levels [1] [2] [3] [4]. Several members of the EAAT family have been described previously. So far, all known EAATs have been reported to transport glutamate and aspartate with a similar affinity. Here, we report that dEAAT2 - a nervous tissue-specific EAAT homologue that we recently identified in the fruit fly Drosophila [5] - is a selective Na(+)-dependent high-affinity aspartate transporter (K(m) = 30 microM). We found that dEAAT2 can also transport L-glutamate but with a much lower affinity (K(m) = 185 microM) and a 10- to 15-fold lower relative efficacy (V(max)/K(m)). Competition experiments showed that the binding of glutamate to this transporter is much weaker than the binding of D- or L-aspartate. As dEAAT2 is the first known EAAT to show this substrate selectivity, it suggests that aspartate may play a specific role in the Drosophila nervous system.

Identification and structural characterization of two genes encoding glutamate transporter homologues differently expressed in the nervous system of Drosophila melanogaster.

In vertebrates, excitatory amino acid transporters (EAATs) are believed to mediate the removal of glutamate released at excitatory synapses and to maintain extracellular concentrations of this neurotransmitter below excitotoxic levels. Glutamate is also used in insects as an excitatory neurotransmitter at the neuromuscular junction and probably in the central nervous system where its role remains to be established. We report the molecular characterization and developmental expression pattern of two Drosophila cDNAs: dEAATI, which has recently been identified as a high affinity glutamate transporter [1], and dEAAT2, a novel protein sharing strong homology to dEAATI and to the mammalian EAAT protein family. The developmental expression pattern of the two Drosophila EAAT genes has been compared by Northern blot analysis and whole-mount in situ hybridizations. The two transporters are transcribed in distinct cell types of the nervous system and are strongly expressed in the adult visual system.