Alexandre Thomas

Identification and Validation of the Methylated TWIST1 and NID2 Genes through Real-Time Methylation-Specific Polymerase Chain Reaction Assays for the Noninvasive Detection of Primary Bladder Cancer in Urine Samples

BACKGROUND Accumulating evidence suggests that DNA methylation markers could serve as sensitive and specific cancer biomarkers. OBJECTIVE To determine whether a panel of methylated genes would have the potential to identify primary bladder cancer (BCa) in voided urine samples. DESIGN, SETTING, AND PARTICIPANTS A pharmacologic unmasking reexpression analysis in BCa cell lines was initially undertaken to unveil candidate methylated genes, which were then evaluated in methylation-specific polymerase chain reaction (MSP) assays performed on DNA extracted from noncancerous and cancerous bladder tissues. The most frequently methylated genes in cancerous tissues, with 100% specificity, were retained for subsequent MSP analysis in DNA extracted from urine samples to build and validate a panel of potential methylated gene markers. Urine samples were prospectively collected at three urologic centres from patients with histologically proven BCa and processed for use in real-time MSP and cytologic analysis. Patients with nonmalignant urologic disorders were included as controls. MEASUREMENTS A urine sample was classified as valid when > or = 10 copies of the gene encoding ß-actin were measured in the urine sediment genomic DNA. Sensitivity, specificity, and predictive values of the MSP and cytology tests were assessed and compared. RESULTS AND LIMITATIONS MSP assays performed on 466 of the 496 (94%) valid urine samples identified two genes, TWIST1 and NID2, that were frequently methylated in urine samples collected from BCa patients, including those with early-stage and low-grade disease. The sensitivity of this two-gene panel (90%) was significantly better than that of cytology (48%), with comparable specificity (93% and 96%, respectively). The positive predictive value and negative predictive value of the two-gene panel was 86% and 95%, respectively. CONCLUSIONS Detection of the methylated TWIST1 and NID2 genes in urine sediments using MSP provides a highly (> or = 90%) sensitive and specific, noninvasive approach for detecting primary BCa. TRIAL REGISTRATION BlCa-001 study - EudraCt 2006-003303-40.

Outcomes Following First-line Endourologic Management of Ureteroenteric Anastomotic Strictures After Urinary Diversion: A Single-center Study

OBJECTIVE To assess the outcomes of patients following a first-line systematic endourologic procedure used to treat ureteroenteric anastomotic strictures (UEAS). MATERIALS AND METHODS All data from patients treated using a first-line endourologic approach for UEAS between 2010 and 2015 were reviewed retrospectively. The following data were analyzed: age, type of urinary diversion, initial symptoms, surgical endoscopic approach (antegrade or retrograde), pre- and postoperative creatinine levels, and postoperative complications and outcomes. Follow-up visits occurred at 6 weeks, 3 months, and 6 months postoperatively, and at least annually thereafter. RESULTS A total of 27 patients (median age: 62.5 years) were included. Overall, 28 UEAS were treated endoscopically (ileal conduit: n = 25; neobladder: n = 3). Most UEAS developed following radical cystectomy for bladder cancer (n = 19). Overall, the endoscopic approach was successful in 20 cases (71.4%). The UEAS length was >1 cm in 21 cases (75%). All UEAS of <1 cm were treated successfully (n = 7). There were three grade II and five grade III complications. The median follow-up period was 25 months. The median creatinine levels before surgery and at last follow-up were 1.3 mg/dL and 0.9 mg/dL, respectively. CONCLUSION An endourologic procedure is a reasonable option for first-line treatment for UEAS and has promising functional outcomes and limited morbidity.

Les agrandissements vésicaux et dérivations

L’agrandissement vesical est la technique chirurgicale de choix pour le traitement de l’incontinence refractaire du patient neurologique sur vessie hyperactive et de petite capacite. L’evaluation de la capacite a s’autosonder et l’apprentissage de cette technique est un prealable indispensable avant l’intervention. La complication a long terme la plus frequente de l’enterocystoplastie d’agrandissement est le calcul de vessie. La plus grave est la perforation vesicale qui peut etre liee soit a un phenomene de surpression, soit a un traumatisme lie a l’autosondage. Son decours est parfois gravissime et doit etre suspecte devant tout abdomen aigu chez un patient porteur d’une enterocystoplasti Le traitement de l’incontinence urinaire masculine par une derivation est exceptionnel. Il ne peut s’envisager que lorsque la vessie et les mecanismes sphincteriens sont detruits et irreversiblement atteints. La vesicostomie est une amelioration de l’agrandissement vesical, permettant d’eviter une cystectomie et la constitution d’un neoreservoir intra-abdominal. Elle offre un excellent taux de continence tout en conservant l’image corporelle du patient.

Modified inside-out transobturator procedure: reply by the authors

Dear Editor, We thank G.H. Page and A.-S. Page for their interesting comment on our study [1]. In our modified TVT-O technique, the tape is shortened to 12 cm and the dissection is reduced, the obturator membrane being no longer perforated either by the scissors or by the guide. The rationale for this reduced dissection was to ensure the anchoring of the shortened tape in the obturator membrane and muscles. Using this modified TVT-O technique, we have observed significantly reduced immediate postoperative groin pain compared with the original TVT-O procedure. As mentioned in the introduction section of our paper, the source of groin pain after transobturator procedures may originate from (1) trauma secondary to the penetration of the dissecting scissors, needles and/or tape into muscular (i.e. obturator and adductor muscles), and/or aponeurotic (i.e. obturator membrane) structures; (2) the foreign body reaction to the tape; (3) possibly owing to proximity to peripheral obturator nerve branches. From the data we have presented, one cannot identify why the modified TVT-O procedure generates less postoperative groin pain than its original counterpart. We believe this reduced groin pain is likely the result of both the minimized dissection and a lesser inflammatory reaction due to a reduced mesh load. Indeed, it is interesting to note that in the group of patients who had undergone the modified TVT-O procedure, postoperative groin pain scores were variable, thus potentially highlighting individual variability in the acute inflammatory reaction to the shorter tape. In order to evaluate the relative contributions of these two mechanisms, in our trial, we would have needed to include a third arm with patients in whom the original TVT-O tape would have been inserted with minimized dissection (no perforation of the obturator with the scissors/guide). With this in mind, it is legitimate to modify the original TVT-O dissection to a reduced one that no longer includes perforation of the obturator membrane with the scissors/guide.