2021 opinion from the CUROPF on THE efficacy and safety of mid-urethral slings used in women WITH urinary stress incontinence.

OBJECTIVE: To determine the usefulness of mid-urethral slings (MUS) in the surgical management of women presenting with urinary stress incontinence (USI) METHOD: A consensus committee of multidisciplinary experts (CUROPF) was convened and focused on PICO questions concerning the efficacy and safety of MUS surgery compared to other procedures and concerning which approach (retropubic (RP) vs transobturator (TO)) should be proposed as a first-line MUS surgery for specific subpopulations (obese; intrinsic sphincteric deficiency (ISD); elderly) RESULTS: As compared to other procedures (urethral bulking agents, traditional slings and open colposuspension), the MUS procedure should be proposed as the first-line surgical therapy (strong agreement). MUS surgery can be associated with complications and proper pre-operative informed consent is mandatory (strong agreement). Mini-slings (SIS/SIMS) should only be proposed in clinical trials (strong agreement). Both RP and TO approaches may be proposed for the insertion of MUS (strong agreement). However, if the woman is willing to accept a moderate increase in per-operative risk, the RP approach should be preferred (strong agreement) since it is associated with higher very long-term cure rates and as it is possible to completely remove the sling surgically if a severe complication occurs. The RP approach should be used for the insertion of MUS in a woman presenting with ISD (strong agreement). Either the RP or TO approach should be used for the insertion of MUS in an obese woman presenting with USI (strong agreement). In very obese women (BMI ≥35-40kg/m2), weight loss should be preferred prior to MUS surgery and bariatric surgery should be discussed (strong agreement) CONCLUSION: The current Opinion provides an appropriate strategy for both the selection of patients and the best therapeutic approach in women presenting with USI.

[Intravesical instillations for inflammatory and sensory chronic bladder diseases: Literature review and guide to clinical practice]. / Instillations endovésicales pour les cystopathies chroniques inflammatoires et douloureuses : revue de la littérature et guide de la pratique clinique.

INTRODUCTION: Inflammatory and sensory chronic bladder diseases have a significant impact on quality of life. These pathologies share alteration of the layer between urine and urothelium, making the use of topical agents appropriate. OBJECTIVES: Review the efficacy and tolerance of intravesical treatments for these pathologies. Give practical guidelines for the use of agents currently available in France. METHOD: A narrative review was performed in March 2021 using PubMed/MEDLINE, Google Scholar and the international guidelines. Pharmaceutical companies and pharmacies were interviewed. RESULTS: Although numerous molecules were tested over the last 5 decades, only dimethylsulfoxyde and glycosaminoglycans are available in France today. Results are promising: response rates are up to 95% and 84% respectively in bladder pain syndrome. In urinary tract infections, glycosaminoglycans could decrease annual number of cystitis by 2.56 (95% confidence interval (CI) -3.86, -1.26; P<0.001) and increase the time to first cystitis recurrence by 130 days (95% CI: 5.84 - 254.26; P=0.04). In radiation cystitis, results could be comparable to hyperbaric oxygen regarding pain and frequency of voiding (-1.31±1.3 visual analogic scale et -1.5±1.4 voiding per day, respectively, at 12 months, P<0.01). However, literature has a low level of evidence. CONCLUSION: Chronic bladder diseases have limited treatment options. Intravesical agents are a good alternative, although their cost is significant and their outcome uncertain.

[Complications of mid-urethral sling - A review from the Committee for Female Urology and Pelviperineology for the French Association of Urology]. / Complications des bandelettes sous urétrales : une revue de la littérature par le Comité d'urologie et pelvipérinéologie de la femme de l'Association française d'urologie.

INTRODUCTION: Placement of a mid-urethral sling is the gold standard in the surgical management of stress urinary incontinence in women in France. The cure rate of this material is no longer to be demonstrated, but the per- and post-operative complications are currently the subject of a growing controversy not only in Europe but also across the Channel and across the Atlantic, having led to the modification of operative indications. In France, recommendations are also evolving with a stricter framework for indications for surgery by multidisciplinary consultation meeting and an obligation for postoperative follow-up in the short and long term. OBJECTIVES: In this context, CUROPF realized a review of the literature bringing together the available scientific evidence concerning the occurrence of per- and post-operative complications relating to the installation of mid urethral sling. The bibliographic search was carried out using the Medline database and 123 articles were selected. RESULTS: Analysis of the data highlights various complications, depending on the implanted material, the patient and the indication for surgery. The retro-pubic mid urethral sling provides more bladder erosion during surgery (up to 14%), more suprapubic pain (up to 4%) and more acute urinary retention (up to 19,7%) and postoperative dysuria (up to 26%). The trans obturator mid-urethral sling is responsible for more vaginal erosion during the operation (up to 10,9%), more lower limb pain of neurological origin (up to 26,7%). The risk of developing over active bladder is similar in both procedures (up to 33%). But these risks of complications must be balanced by the strong impact of urinary incontinence surgery on the overall quality of life of these women. CONCLUSION: Thus, surgical failure and long term complications exist but should not limit the surgical management of stress urinary incontinence with mid urethral tape. Women should be treated with individualized decision-making process and long-term follow -up is necessary.

[Vaginal LASER therapy for genito-urinary disorders: A systematic review and statement from the Committee for Female Urology and Pelviperineology of the French Association of Urology]. / Utilisation du LASER vaginal pour le traitement des pathologies génito-urinaires : revue systématique de la littérature et position du CUROPF.

INTRODUCTION: Vaginal LASER therapy is increasingly used in the field of urogynecology, but several points remain unclear. Our goal was to produce a systematic review of available evidence and provide a critical appraisal of available data. METHODS: A systematic review until march 2020 was conducted using PubMed/MEDLINE, Cochrane and Embase databases. All studies about vaginal LASER use in the field of urogynecology were included. RESULTS: Forty studies have been included (8 for genitourinary syndrome of menopause, 19 for stress urinary incontinence, 3 for overactive bladder, 7 for urogenital prolapse, 3 for other indications). Data were heterogeneous, and level of evidence was weak or very weak. Few studies were comparative, and only 3 were randomized). Mild improvement of symptoms and quality of life and limited satisfaction were seen for genitourinary syndrome, stress urinary incontinence, overactive bladder and prolapse. Few adverse events were reported. However, major methodological biases were noted regarding efficacy and safety evaluation. No long-term results were available. CONCLUSIONS: While Vaginal LASER therapy seem to provide encouraging results, the level of evidence supporting its use was weak, especially regarding long-term outcomes. Studies of better quality are warranted before any recommendation can be made. Current use should be limited to clinical research.

[When to introduce hormone therapy after total prostatectomy with positive lymph nodes? Study of the factors influencing the time of introduction of hormone therapy]. / Quand introduire une hormonothérapie après prostatectomie totale avec curage ganglionnaire positif ? Étude des facteurs influençant le délai d'introduction de l'hormonothérapie.

INTRODUCTION: Adjuvant hormone therapy is the standard treatment after total prostatectomy with positive lymph node. However, this treatment has side effects and at the time of the PSA era and extensive lymph node dissection, this principle is questioned. The aim of this study is to describe the oncological characteristics of patients that may explain the delay in introducing hormone therapy in patients with positive lymph node. METHODS: Monocentric, retrospective study of 161 patients from November 1988 to February 2018 in a single French University Hospital, having undergone radical prostatectomy with positive lymph nodes on pathology. For each patient, preoperative data (age, clinical stage, biopsy results, d'Amico classification) and postoperative data (pathological results, number of lymph nodes removed, number of positive lympnodes, recurrence free survival, specific survival and overall survival) were collected. The date of introduction of hormone therapy was noted and survival without hormonal therapy was established according to the Kaplan Meier curve. The pre- and post-operative oncological factors that could influence hormone therapy introduction were investigated with Chi2 and Student tests (statistically significant when P<0.05). RESULTS: The mean number of lymph nodes removed was 12 [1-40]. The mean number of positive lymph nodes was 2.5 [1-24], the mean percentage of positive lymph nodes was 25% (2.5-100). After a mean follow-up of 95 months (3-354), 88 patients (54.6%) had no hormonal treatment. The average time to hormonal treatment was 40 months [0-310]. At 3 years, survival without hormone therapy was 52% and 51% at 5 years. Only the percentage of positive lymphnodes appeared to be a significant predictor of the introduction of hormone therapy. (29.32% vs. 21.99%, P=0.047). Hormone-free survival was significantly higher in patients with lymph node involvement less than 25% (P<0.0001) or with less than 2 positive lymph nodes (P=0.0294). CONCLUSION: Lymph node invasion is a factor of poor prognosis after total prostatectomy and leads to introduce hormone therapy. Our study identified the percentage and number of positive lymph nodes as factors that identify patients who may be delayed in introducing this hormone therapy. LEVEL OF PROOF: 3.

[Prognostic factors of upper tract urothelial carcinoma]. / Facteurs pronostiques des tumeurs de la voie excrétrice urinaire supérieure.

INTRODUCTION: Upper urinary tract urothelial carcinoma (UTUC) is a rare disease. Thus, little evidence-based data are available to guide clinical decision-making. The aim of the study was to provide an overview of the currently available prognostic factors for UTUC. MATERIAL AND METHODS: A systematic literature search was conducted using the PubMed databases to identify original articles regarding prognostic factors in patients with UTUC. RESULTS: We divided the prognostic factors for UTUC in four different categories: clinical factors, preoperative characteristics, intraoperative/surgical factors and postoperative/pathologic factors. Prognostic factors described in order of importance are: tumor stage and grade, lymph node involvement, a concomitant cis, age at the diagnostic, lymphovascular invasion, tumor architecture and necrosis, tumor location and multifocality, gender. The impact of obesity, smoking and other comorbidities (ECOG, ASA) on outcomes has been recently reported but needs to be validated. The endoscopic approach of distal ureter management during radical nephroureterectomy has been shown to be at higher risk of bladder recurrence. CONCLUSION: The incorporation of such prognosticators into clinical prediction models might help to guide decision-making with regard to timing of surveillance, type of treatment, performance of lymphadenectomy, and consideration of neoadjuvant or adjuvant systemic therapies.

[Aetiology and management of iatrogenic injury of the ureter: a review]. / Étiologie et traitements des plaies iatrogènes de l'uretère : analyse de la littérature.

OBJECTIVE: Ureteric injuries (IU) are common complications occurring during abdomino-pelvic surgical procedures. Our aim was to review risk factors, treatment and methods of prevention of these iatrogenic UI. MATERIAL AND METHODS: A literature review in English and French by Medline(®) was performed using the keywords: ureter; iatrogenic; injury; ureteroscopy; morbidity and endoscopy. RESULTS: The analysis of the epidemiology of IU shows that the first two causes are gynecological and urological surgery. In 80% of cases, the pelvic ureter was concerned. Mechanisms of injury were essentially ligation, section and ischemia by altering the ureteral vasculature. The main risk factors found were pelvic inflammation (endometriosis, radiation…) and the occurrence of bleeding during surgery. In the presence of risk factors, placing a double J stent or a CT may be useful preoperatively. The choice of reparation technique depended on the location of the PU, the circumstances of the occurrence and experience of the surgical team. CONCLUSION: Pelvic surgery is a provider of iatrogenic PU. Knowledge of the management of PU once occurred must be mastered before carrying out any risk surgery.

[Prebiopsy multiparametric MRI of the prostate: the end of randomized biopsies?]. / IRM mutiparamétrique de la prostate avant biopsies : la fin des biopsies systématisées ?

OBJECTIVE: To evaluate the value of multiparametric MRI-targeted prostate biopsies in patients with suspected low-risk prostate cancer. PATIENTS AND METHOD: Patients with normal digital rectal examination and a PSA level between 4 and 10 ng/mL were prospectively included. A multiparametric MRI of the prostate was performed prospectively before the biopsies. 12-core randomized biopsies were performed, with additional targeted samples in each suspicious area identified on MRI. Detected cancers and their histological characteristics were compared between those two biopsy protocols. A micro focal cancer (MFC) was defined by the presence of less than 4mm of Gleason score 3+3 cancer on a single core. RESULTS: Seventy-one consecutive patients were included. The overall detection rate was of 53% (38/71). It was of 70% (26/37) in the presence of suspicious area on MRI versus 35% (12/34) in the absence of any suspicious area (P=0.004). MRI-targeted biopsies alone detected three cancers, none of which was a MFC. 12-core biopsies alone detected 14 cancers, including ten MFC (71%). In 21 patients, prostate cancer was detected by both the MRI-targeted and 12-core biopsies. The Gleason score in the MRI-targeted area was the highest Gleason score in 90% of the cases. It was high (>6) in 76% (16/21) of the patients. CONCLUSIONS: MRI-targeted biopsies detected less micro focal cancers than randomized 12-core biopsies. They did not seem however to decrease the detection of clinically significant cancers.

Differential gene expression in nematode-induced feeding structures of transgenic plants harbouring promoter-gusA fusion constructs.

Sedentary plant-parasitic nematodes are able to induce specialized feeding structures in the root system of their host plants by triggering a series of dramatic cellular responses. These changes presumably are accompanied by a reprogramming of gene expression. To monitor such changes, a variety of promoter-gusA fusion constructs were introduced into Arabidopsis and tobacco. Transgenic plants were analysed histochemically for GUS activity in the nematode feeding structures after infection with either Heterodera schachtii or Meloidogyne incognita. Promoters of the Cauliflower Mosaic Virus 35S gene, the bacterial nopaline synthase, rooting loci (rol) and T-cyt genes and the plant-derived phenylalanine ammonia-lyase I gene, which are highly active in non-infected roots, were all downregulated in the feeding structures as indicated by the strong decrease of GUS activity inside these structures. Less stringent downregulation was observed with chimeric gusA fusion constructs harbouring truncated rolB and rolC promoter sequences. Similar observations were made with transgenic Arabidopsis lines that carried randomly integrated promoterless gusA constructs to identify regulatory sequences in the plant genome. Most of the lines that were selected for expression in the root vascular cylinder demonstrated local downregulation in feeding structures after infection with H. schachtii. The reverse pattern of GUS activity, a blue feeding structure amidst unstained root cells, was also found in several lines. However, GUS activity that was entirely specific for the feeding structures was not observed. Our data show that the expression of a large number of genes is influenced during the development of the nematode feeding structures.

Regulatory sequences of Arabidopsis drive reporter gene expression in nematode feeding structures.

In the quest for plant regulatory sequences capable of driving nematode-triggered effector gene expression in feeding structures, we show that promoter tagging is a valuable tool. A large collection of transgenic Arabidopsis plants was generated. They were transformed with a beta-glucuronidase gene functioning as a promoter tag. Three T-DNA constructs, pGV1047, p delta gusBin19, and pMOG553, were used. Early responses to nematode invasion were of primary interest. Six lines exhibiting beta-glucuronidase activity in syncytia induced by the beet cyst nematode were studied. Reporter gene activation was also identified in galls induced by root knot and ectoparasitic nematodes. Time-course studies revealed that all six tags were differentially activated during the development of the feeding structure. T-DNA-flanking regions responsible for the observed responses after nematode infection were isolated and characterized for promoter activity.