Contribution of canine olfaction in the diagnostic strategy of intermediate and high-risk prostate cancer: a double-blind validation study.

PURPOSE: Prostate cancer diagnosis is confirmed with a prostate biopsy, which is invasive and unpleasant. Adding canine olfaction into the diagnostic protocol could help avoid unnecessary biopsies. This study aims to determine whether dogs can identify ISUP (International Society of Urological Pathology) > 2 prostate cancer. MATERIALS AND METHODS: This double-blind, prospective, validation study included men with suspected prostate cancer between November 2022 and April 2023 in France. They were classified into two groups according to their prostate biopsy results; cases (ISUP > 2) and controls (ISUP < 1 or negative). Seven dogs analyzed their urine. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for canine olfactory detection of ISUP ≥ 2 prostate cancer were measured and compared with that of prostate MRI versus prostate biopsy. RESULTS: The seven dogs analyzed 151 urine samples, 78 from the case group and 73 from the control group. The minimal and maximal observed values were 54% and 86% for sensitivity, and 69% and 88% for specificity. Five dogs had a sensitivity above 73% and six dogs had a specificity above 75%. The kappa coefficient quantifying agreement between the biopsy result and the MRI PI-RADS ≥ 3 was 0.17 [- 0.14; 0.17], 0.20 [0.02-0.33] for PI-RADS ≥ 4 and 0.64 [0.5-0.75] for canine olfaction meaning there is a substantial agreement between the biopsy result and canine olfaction. CONCLUSIONS: Based on this study, the non-invasive and safe canine olfaction technique seems reliable for diagnosing ISUP ≥ 2 prostate cancer. Combined with prostate MRI, it may improve the decision-making process when choosing to perform prostate biopsies.

Risk Factors for Artificial Urinary Sphincter Explantation and Erosion in Male Nonneurological Patients.

PURPOSE: This study was performed to assess the risk factors for artificial urinary sphincter (AUS) explantation in a large multicenter cohort. METHODS: We retrospectively reviewed the medical records for all 1,233 implantations of the AMS-800 AUS device in male nonneurological patients from 2005 to 2020 across 13 French centers. Patients with neurological conditions were excluded from the study. To identify factors associated with explantation-free survival, survival analysis was performed. Explantation was defined as the complete removal of the device, whereas revision referred to the replacement of the device or its components. RESULTS: The study included 1,107 patients, of whom 281 underwent AUS explantation. The median survival without explantation was 83 months. The leading causes of explantation were infection and erosion. Univariate analysis revealed several significant risk factors for explantation: age above 75 years (34.6% in the explanted group vs. 25.8% in the nonexplanted group, P=0.007), history of radiotherapy (43.5% vs. 31.3%, P=0.001), and anticoagulant use (15% vs. 8.6%, P<0.001). In logistic regression analysis, the only significant risk factor was previous radiotherapy (odds ratio [OR], 2.05; P<0.05). Cox proportional hazards analysis revealed 2 factors associated with earlier explantation: transcorporal cuff implantation (hazard ratio [HR], 2.67; P=0.01) and the annual caseload of the center (HR, 1.08; P=0.02). When specifically examining explantation due to erosion, radiotherapy was the sole factor significantly associated with the risk of erosion (OR, 2.47; P<0.05) as well as earlier erosion (HR, 1.90; P=0.039). CONCLUSION: In this series, conducted in a real-world setting across multiple centers with different volumes and levels of expertise, the median survival without AUS explantation was 83 months. This study confirms that radiotherapy represents the primary independent risk factor for AUS erosion in male nonneurological patients.

Primary implantation of an artificial urinary sphincter using the perineal and penoscrotal approaches: Functional results and assessment of reoperative procedures.

INTRODUCTION: Artificial urinary sphincter (AUS) is the standard treatment for severe stress urinary incontinence in men. While the perineal access is considered the gold standard, some authors have proposed penoscrotal AUS in order to facilitate the procedure. The main objective of our study was to evaluate the duration of survival without revision surgery (SSRC) according to the surgical approach for primary implantation. MATERIAL AND METHODS: Data from 1179 patients implanted in France between 1991 and 2020 with an AMS 800 AUS were retrospectively analyzed. A total of 762 men were implanted perineally (VP) and 417 penoscrotally (VPS). RESULTS: Median follow-up was 20 vs. 25months respectively. The groups were equivalent overall, apart from the use of anticoagulants (11% VP vs. 6.3% VPS P=0.014). In our population, 54% patients were considered as "dry" in the case of VPS vs. 42% for VP. There was no significant difference in terms of survival time without reoperation, revision, replacement or explantation. In univariate and multivariate analysis, age over 70years was predictive of more reinterventions, whereas the use of a 4.5cm cuff was protective, with hazard ratios of 1.42 (P=0.001) and 0.78 (P=0.04), respectively. CONCLUSION: The penoscrotal approach does not appear to be associated with more complications, has good functional results and no significant difference in reoperation-free survival. A prospective multicenter non-inferiority study could be of interest to confirm our findings.

Primary bladder neck obstruction in men: The importance of urodynamic assessment and cystourethrography in measuring its severity.

OBJECTIVE: Primary bladder neck obstruction (PBNO) is a condition primarily affecting young men, characterized by obstruction at the bladder neck, leading to lower urinary tract symptoms. The aim of this study was to identify a correlation between the severity of bladder neck opening impairment and urinary symptoms by means of urodynamic studies. MATERIALS AND METHODS: A retrospective analysis was conducted in adult males diagnosed with PBNO at a university neurourology department between 2015 and 2022 who underwent voiding cystourethrography (VCUG) and pressure-flow studies. The cohort was divided into two groups: absence of bladder neck opening on VCUG (Group A) and incomplete bladder neck opening (Group B). RESULTS: Out of the 82 patients with PBNO screened, 53 were included in the analysis. Nocturia was the only symptom more prevalent in Group A (65% in Group A vs. 30% in Group B, p = 0.02) but scores and subscores of the Urinary Symptom Profile questionnaire were not different between groups. In addition, the detrusor pressure at a maximum flow rate (PdetQmax), bladder outlet obstruction index (BOOI), and bladder contractility index (BCI) were higher in Group A than in Group B [PdetQmax (A = 93.7 ± 53.7 cmH2O vs. B = 65.7 ± 26.4 cmH2O; p = 0.01)-BOOI (A = 77 ± 58.3 vs. B = 48 ± 25.7; p = 0.03)-BCI (A = 136 ± 51.3 vs. B = 110 ± 41.7; p = 0.04)]. CONCLUSION: This study demonstrates a significant association between the extent of bladder neck opening impairment observed on VCUG and obstruction and contraction urodynamic parameters, but no association with the severity of urinary symptoms. Future studies should evaluate the predictive value of treatment response and the occurrence of complications based on clinical and urodynamic parameters.

Diagnosis and management of complications following pelvic organ prolapse surgery using a synthetic mesh: French national guidelines for clinical practice.

Complications associated with pelvic organ prolapse (POP) surgery using a synthetic non-absorbable mesh are uncommon (<5%) but may be severe and may hugely diminish the quality of life of some women. In drawing up these multidisciplinary clinical practice recommendations, the French National Authority for Health (Haute Autorité de santé, HAS) conducted an exhaustive review of the literature concerning the diagnosis, prevention, and management of complications associated with POP surgery using a synthetic mesh. Each recommendation for practice was allocated a grade (A,B or C; or expert opinion (EO)), which depends on the level of evidence (clinical practice guidelines). PREOPERATIVE PATIENTS' INFORMATION: Each patient must be informed concerning the risks associated with POP surgery (EO). HEMORRHAGE, HEMATOMA: Vaginal infiltration using a vasoconstrictive solution is not recommended during POP surgery by the vaginal route (grade C). The placement of vaginal packing is not recommended following POP surgery by the vaginal route (grade C). During laparoscopic sacral colpopexy, when the promontory seems highly dangerous or when severe adhesions prevent access to the anterior vertebral ligament, alternative surgical techniques should be discussed per operatively, including colpopexy by lateral mesh laparoscopic suspension, uterosacral ligament suspension, open abdominal mesh surgery, or surgery by the vaginal route (EO). BLADDER INJURY: When a bladder injury is diagnosed, bladder repair by suturing is recommended, using a slow resorption suture thread, plus monitoring of the permeability of the ureters (before and after bladder repair) when the injury is located at the level of the trigone (EO). When a bladder injury is diagnosed, after bladder repair, a prosthetic mesh (polypropylene or polyester material) can be placed between the repaired bladder and the vagina, if the quality of the suturing is good. The recommended duration of bladder catheterization following bladder repair in this context of POP mesh surgery is from 5 to 10 days (EO). URETER INJURY: After ureteral repair, it is possible to continue sacral colpopexy and place the mesh if it is located away from the ureteral repair (EO). RECTAL INJURY: Regardless of the approach, when a rectal injury occurs, a posterior mesh should not be placed between the rectum and the vagina wall (EO). Concerning the anterior mesh, it is recommended to use a macroporous monofilament polypropylene mesh (EO). A polyester mesh is not recommended in this situation (EO). VAGINAL WALL INJURY: After vaginal wall repair, an anterior or a posterior microporous polypropylene mesh can be placed, if the quality of the repair is found to be satisfactory (EO). A polyester mesh should not be used after vaginal wall repair (EO). MESH INFECTION (ABSCESS, CELLULITIS, SPONDYLODISCITIS): Regardless of the surgical approach, intravenous antibiotic prophylaxis is recommended (aminopenicillin + beta-lactamase inhibitor: 30 min before skin incision +/- repeated after 2 h if surgery lasts longer) (EO). When spondylodiscitis is diagnosed following sacral colpopexy, treatment should be discussed by a multidisciplinary group, including especially spine specialists (rheumatologists, orthopedists, neurosurgeons) and infectious disease specialists (EO). When a pelvic abscess occurs following synthetic mesh sacral colpopexy, it is recommended to carry out complete mesh removal as soon as possible, combined with collection of intraoperative bacteriological samples, drainage of the collection and targeted antibiotic therapy (EO). Non-surgical conservative management with antibiotic therapy may be an option (EO) in certain conditions (absence of signs of sepsis, macroporous monofilament polypropylene type 1 mesh, prior microbiological documentation and multidisciplinary consultation for the choice of type and duration of antibiotic therapy), associated with close monitoring of the patient. BOWEL OCCLUSION RELATED TO NON-CLOSURE OF THE PERITONEUM: Peritoneal closure is recommended after placement of a synthetic mesh by the abdominal approach (EO). URINARY RETENTION: Preoperative urodynamics is recommended in women presenting with urinary symptoms (bladder outlet obstruction symptoms, overactive bladder syndrome or incontinence) (EO). It is recommended to remove the bladder catheter at the end of the procedure or within 48 h after POP surgery (grade B). Bladder emptying and post-void residual should be checked following POP surgery, before discharge (EO). When postoperative urine retention occurs after POP surgery, it is recommended to carry out indwelling catheterization and to prefer intermittent self-catheterization (EO). POSTOPERATIVE PAIN: Before POP surgery, the patient should be asked about risk factors for prolonged and chronic postoperative pain (pain sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Concerning the prevention of postoperative pain, it is recommended to carry out a pre-, per- and postoperative multimodal pain treatment (grade B). The use of ketamine intraoperatively is recommended for the prevention of chronic postoperative pelvic pain, especially for patients with risk factors (preoperative painful sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Postoperative prescription of opioids should be limited in quantity and duration (grade C). When acute neuropathic pain (sciatalgia or pudendal neuralgia) resistant to level I and II analgesics occurs following sacrospinous fixation, a reintervention is recommended for suspension suture removal (EO). When chronic postoperative pain occurs after POP surgery, it is recommended to systematically seek arguments in favor of neuropathic pain with the DN4 questionnaire (EO). When chronic postoperative pelvic pain occurs after POP surgery, central sensitization should be identified since it requires a consultation in a chronic pain department (EO). Concerning myofascial pain syndrome (clinical pain condition associated with increased muscle tension caused by myofascial trigger points), when chronic postoperative pain occurs after POP surgery, it is recommended to examine the levator ani, piriformis and obturator internus muscles, so as to identify trigger points on the pathway of the synthetic mesh (EO). Pelvic floor muscle training with muscle relaxation is recommended when myofascial pain syndrome is associated with chronic postoperative pain following POP surgery (EO). After failure of pelvic floor muscle training (3 months), it is recommended to discuss surgical removal of the synthetic mesh, during a multidisciplinary discussion group meeting (EO). Partial removal of synthetic mesh is indicated when a trigger point is located on the pathway of the mesh (EO). Total removal of synthetic mesh should be discussed during a multidisciplinary discussion group meeting when diffuse (no trigger point) chronic postoperative pain occurs following POP surgery, with or without central sensitization or neuropathic pain syndromes (EO). POSTOPERATIVE DYSPAREUNIA: When de novo postoperative dyspareunia occurs after POP surgery, surgical removal of the mesh should be discussed (EO). VAGINAL MESH EXPOSURE: To reduce the risk of vaginal mesh exposure, when hysterectomy is required during sacral colpopexy, subtotal hysterectomy is recommended (grade C). When asymptomatic vaginal macroporous monofilament polypropylene mesh exposure occurs, systematic imaging is not recommended. When vaginal polyester mesh exposure occurs, pelvic +/- lumbar MRI (EO) should be used to look for an abscess or spondylodiscitis, given the greater risk of infection associated with this type of material. When asymptomatic vaginal mesh exposure of less than 1 cm2 occurs in a woman with no sexual intercourse, the patient should be offered observation (no treatment) or local estrogen therapy (EO). However, if the patient wishes, partial excision of the mesh can be offered. When asymptomatic vaginal mesh exposure of more than 1 cm2 occurs or if the woman has sexual intercourse, or if it is a polyester prosthesis, partial mesh excision, either immediately or after local estrogen therapy, should be offered (EO). When symptomatic vaginal mesh exposure occurs, but without infectious complications, surgical removal of the exposed part of the mesh by the vaginal route is recommended (EO), and not systematic complete excision of the mesh. Following sacral colpopexy, complete removal of the mesh (by laparoscopy or laparotomy) is only required in the presence of an abscess or spondylodiscitis (EO). When vaginal mesh exposure recurs after a first reoperation, the patient should be treated by an experienced team specialized in this type of complication (EO). SUTURE THREAD VAGINAL EXPOSURE: For women presenting with vaginal exposure to non-absorbable suture thread following POP surgery with mesh reinforcement, the suture thread should be removed by the vaginal route (EO). Removal of the surrounding mesh is only recommended when vaginal mesh exposure or associated abscess is diagnosed. BLADDER AND URETERAL MESH EXPOSURE: When bladder mesh exposure occurs, removal of the exposed part of the mesh is recommended (grade B). Both alternatives (total or partial mesh removal) should be discussed with the patient and should be debated during a multidisciplinary discussion group meeting (EO).

Serious complications and recurrences after retropubic vs transobturator midurethral sling procedures for 2682 patients in the VIGI-MESH register.

BACKGROUND: Midurethral slings are the gold standard for treating stress urinary incontinence, but their complications may raise concerns. Complications may differ by the approach used to place them. OBJECTIVE: This study aimed to compare serious complications and reoperations for recurrence after midurethral sling procedures when using the retropubic vs the transobturator route for female stress urinary incontinence. STUDY DESIGN: This analysis was of patients included in the French, multicenter VIGI-MESH register since February 2017 who received a midurethral sling for female stress urinary incontinence either by the retropubic or the transobturator route and excluded patients with single-incision slings. Follow-up continued until October 2021. Serious complications (Clavien-Dindo classification ≥ grade III) attributable to the midurethral sling and reoperations for recurrence were compared using Cox proportional hazard models including any associated surgery (hysterectomy or prolapse) and a frailty term to consider the center effect. Baseline differences were balanced by propensity score weighting. Analyses using the propensity score and Cox models were adjusted for baseline differences, center effect, and associated surgery. RESULTS: A total of 1830 participants received a retropubic sling and 852 received a transobturator sling in 27 French centers that were placed by 167 surgeons. The cumulative 2-year estimate of serious complications was 5.8% (95% confidence interval, 4.8-7.0) in the retropubic group and 2.9% (95% confidence interval, 1.9-4.3) in the transobturator group, that is, after adjustment, half of the retropubic group was affected (adjusted hazard ratio, 0.41; 95% confidence interval, 0.3-0.6). The cumulative 2-year estimate of reoperation for recurrence of stress urinary incontinence was 2.7% (95% confidence interval, 2.0-3.6) in the retropubic group and 2.8% (95% confidence interval, 1.7-4.2) in the transobturator group with risk for revision for recurrence being higher in the transobturator group after adjustment (adjusted hazard ratio, 1.9; 95% confidence interval, 1.2-2.9); this surplus risk disappeared after exclusion of the patients with a previous surgery for stress urinary incontinence. CONCLUSION: The transobturator route for midurethral sling placement is associated with a lower risk for serious complications but a higher risk for surgical reoperation for recurrence than the retropubic route. Despite the large number of surgeons involved, these risks were low. The data are therefore reassuring.

Which revision strategy is the best for non-mechanical failure of male artificial urinary sphincter?

PURPOSE: Persistence or recurrence of stress urinary incontinence (prSUI) after artificial urinary sphincter (AUS) implantation may be secondary to non-mechanical failure (NOMECA). It have for long been assumed to result from urethral atrophy. Its existence is now debated. As the pathophysiology of NOMECA is not elucidated, the most appropriate management remains unclear. We aimed to compare the several revision techniques for NOMECA of AUS in men. METHODS: NOMECA was defined as prSUI, with normally functioning device, no erosion, infection or fluid loss. Exclusion criteria were neurogenic SUI, revision or explantation for other causes. From 1991 to 2022, 143 AUS revisions for NOMECA, including 99 cuff DOWNSIZING, 10 cuff repositioning (RELOC), 13 TANDEM-CUFF placement, 18 cuff changing (CHANGE), three increasing balloon pressure (BALLOON-UP), were performed in 10 centers. BALLOON-UP patients weren't included in comparative analysis due to small sample size. All components could be changed during the revision. Patients were also categorized in COMPLETE-CHANGE vs. PARTIAL-CHANGE of the device. RESULTS: The three-months complete continence rate was 70.8% with a significant difference between RELOC and DOWNSIZING groups (p = 0.04). COMPLETE CHANGE was significantly associated with complete continence status at three months in multivariate analysis (83.3% vs. 63.3%, OR = 2.7; CI 95% [1.1-7.1], p = 0.03). Estimated five-year reoperation-free and explantation-free survival were respectively 63.4% and 75.9% (p = 0.16; p = 0.30). Those were significantly longer in COMPLETE-CHANGE vs PARTIAL-CHANGE (82.2% vs. 69.6%, p = 0.03); (71.2% vs. 58.2%, p = 0.047). CONCLUSIONS: AUS revision for prSUI due to NOMECA yields satisfactory outcomes regardless of the technique used. We observed better functional outcomes when repositioning the new cuff. COMPLETE-CHANGE may improve functional outcomes, explantation-free and reoperation-free survivals.

Transcriptomic Profiling of Upper Tract Urothelial Carcinoma: Bladder Cancer Consensus Classification Relevance, Molecular Heterogeneity, and Differential Immune Signatures.

Analyses of large transcriptomics data sets of muscle-invasive bladder cancer (MIBC) have led to a consensus classification. Molecular subtypes of upper tract urothelial carcinomas (UTUCs) are less known. Our objective was to determine the relevance of the consensus classification in UTUCs by characterizing a novel cohort of surgically treated ≥pT1 tumors. Using immunohistochemistry (IHC), subtype markers GATA3-CK5/6-TUBB2B in multiplex, CK20, p16, Ki67, mismatch repair system proteins, and PD-L1 were evaluated. Heterogeneity was assessed morphologically and/or with subtype IHC. FGFR3 mutations were identified by pyrosequencing. We performed 3'RNA sequencing of each tumor, with multisampling in heterogeneous cases. Consensus classes, unsupervised groups, and microenvironment cell abundance were determined using gene expression. Most of the 66 patients were men (77.3%), with pT1 (n = 23, 34.8%) or pT2-4 stage UTUC (n = 43, 65.2%). FGFR3 mutations and mismatch repair-deficient status were identified in 40% and 4.7% of cases, respectively. Consensus subtypes robustly classified UTUCs and reflected intrinsic subgroups. All pT1 tumors were classified as luminal papillary (LumP). Combining our consensus classification results with those of previously published UTUC cohorts, LumP tumors represented 57.2% of ≥pT2 UTUCs, which was significantly higher than MIBCs. Ten patients (15.2%) harbored areas of distinct subtypes. Consensus classes were associated with FGFR3 mutations, stage, morphology, and IHC. The majority of LumP tumors were characterized by low immune infiltration and PD-L1 expression, in particular, if FGFR3 mutated. Our study shows that MIBC consensus classification robustly classified UTUCs and highlighted intratumoral molecular heterogeneity. The proportion of LumP was significantly higher in UTUCs than in MIBCs. Most LumP tumors showed low immune infiltration and PD-L1 expression and high proportion of FGFR3 mutations. These findings suggest differential response to novel therapies between patients with UTUC and those with MIBC.

Efficacy, Safety, and Reoperation-free Survival of Artificial Urinary Sphincter in Non-neurological Male Patients over 75 Years of Age.

Background: Artificial urinary sphincter (AUS) is a gold standard treatment in male stress urinary incontinence but remains poorly used in elderly patients. Objective: To assess the efficacy, safety, and reoperation-free survival of AUS implantation in male patients over 75 yr of age. Design setting and participants: We retrospectively reviewed the charts of all 1233 non-neurological male AUS implantations between 2005 and 2020 at 13 French centers. We compared 330 patients ≥75 yr old (GROUP75+) with 903 patients <75 yr old (GROUP75-) at the time of AUS implantation. Outcome measurements and statistical analysis: Our primary endpoint was social continence at 3 mo defined as the use of one or fewer pad daily. We used Kaplan-Meier analyses to assess reoperation-free survival. We sought factors of erosion using logistic regression. Results and limitations: Early postoperative continence was comparable in both groups (74.4% vs 80.1%, p = 0.114). We observed a higher rate of postoperative complications in GROUP75+ (18.8% vs 12.6%, p = 0.014), but the complications were more frequently of low grade in GROUP75+ (p = 0.025). The overall reoperation-free survival was similar (p = 0.076) after a median follow-up of 2 yr. However, patients in GROUP75+ had poorer explantation-free survival (p < 0.0001). A history of radiotherapy was a predictive factor of erosion (odds ratio [OR] = 5.31, p < 0.01), but age was not (OR = 1.08, p = 0.87). Unfortunately, our dataset did not include a systematic geriatric evaluation. Conclusions: AUS in elderly patients appears to be an effective option to treat stress urinary incontinence. However, we observed more postoperative complications and explantations, although age was not associated with the onset of erosion. A prospective study is required to determine whether a geriatric evaluation would be an effective strategy to select patients before surgery. Patient summary: In this study, we looked at outcomes of artificial urinary sphincter in elderly men in a large population. We found satisfying efficacy but slightly more postoperative complications and device infections.

Clinical outcomes of adapted hypofractionated radiotherapy for bladder cancer in elderly patients.

OBJECTIVE: To investigate the feasibility, efficacy, and safety of trimodal therapy (TMT) using a bifractionated split-course hypofractionated radiotherapy (RT) for non-metastatic muscle-invasive bladder cancer (MIBC) in elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the characteristics and outcomes of patients aged >75 years with non-metastatic MIBC suitable or not for radical cystectomy (RC) and treated with transurethral resection of bladder tumour followed by concomitant radio-chemotherapy (platinum salt and 5-fluorouracil) at two institutions (Saint Louis Hospital, Paris, France and European Georges Pompidou Hospital, Paris, France) between 1990 and 2021. RT consisted of an adapted bifractionated split-course hypofractionated RT. Acute toxicities were reported according to Common Terminology Criteria for Adverse Events version 5.0 and late toxicities were reported according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. The primary end-point was overall survival (OS). Secondary end-points included other survivals outcomes and safety. RESULTS: A total of 122 patients were identified, with a median (range) follow-up of 51.1 (0.5-210.8) months. In all, 83.5% of patients completed radio-chemotherapy. The OS rate was 61.7% at 3 years and 51.2% at 5 years. In multivariate analysis, the completion of RT and concomitant chemotherapy were significantly associated with better OS and cancer-specific survival. For patients fit for RC, a complete histological response was achieved for 77 patients (91.7%) with radio-chemotherapy and the bladder conservation rate was 90.5%. Acute and late Grade ≥3 toxicities were <5%. CONCLUSION: Bifractionated split-course hypofractionated RT with concomitant chemotherapy regimen appears to be well-tolerated and effective. Trimodal treatment seems to be a curative option for elderly patients unfit for radical surgery compared with palliative care and may contribute to improved survival in these patients.

Effect of bladder filling volume on detrusor contractility in men with bladder outlet obstruction.

INTRODUCTION: Bladder outlet obstruction alters detrusor contractility, reducing the bladder's ability to respond to large filling with a risk of urinary retention. The objective was to assess the effect of bladder filling volume on detrusor contractility in men with bladder outlet obstruction. METHODS: A prospective multicenter study in two pelviperineology departments. Male patients eligible for urodynamics (IPSS score > 7) were included from January to July 2022. In case of absence of bladder outlet obstruction on pressure-flow studies, they were secondarily excluded. The primary endpoint was the maximum isometric detrusor pressure during a stop-test, corresponding to detrusor contractility, measured at 3 filling volumes (50%, 75%, and 100% of cystometric capacity). RESULTS: Fifty-two patients performed urodynamics, of whom 12 were excluded because of lack of obstruction or inability to perform the stop-test. Detrusor contractility was significantly higher for a 75% bladder filling than 50% and for a 75% filling than 100%, with a mean difference of 19.5; confidence interval (CI) 95% [14.3; 24.8] and 12.2; CI 95% [6.9; 17.5] cmH2 O respectively (p < 0,01). CONCLUSION: In case of bladder outlet obstruction in men, detrusor contractility depends on bladder filling volume, with reduced contractility when the bladder was underfilled or overfilled. This phenomenon could help to explain the mechanisms of urinary retention in men with bladder outlet obstruction.

Lymph Node Dissection During Radical Nephro-Ureterectomy for Upper Tract Urothelial Carcinoma: A Review.

Although lymphonodal dissection is well-accepted for muscle-invasive bladder cancer management, its role is still debated during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The aim of this study was to summarize the current knowledge concerning the indication, anatomical template, prognostic, and therapeutic roles of lymph node dissection (LND) performed at the time of RNU. Quality control markers, such as the number of lymph nodes (LN) removed, lymph node density, and safety of the different surgical approaches, were assessed. We performed a narrative review using the PubMed and ClinicalTrials.gov databases. We identified and analyzed articles based on the practice and the role of lymph node dissection for non-metastatic UTUC. There are no clear guidelines regarding the indication of LND for UTUC, but aggressive tumors may beneficiate from lymphadenectomy since lymph node invasion is a clear independent poor prognostic factor, allowing for adjuvant treatments. It seems that an extended lymphadenectomy may provide therapeutic advantages as a higher number of nodes removed may be related to the removal of undetected LNs micrometastases and a subsequent improvement in recurrence rate and cancer-specific survival. Clear anatomical templates are thus needed based on the location and the laterality of the primary tumor.

Current Advances in Immune Checkpoint Inhibition and Clinical Genomics in Upper Tract Urothelial Carcinoma: State of the Art.

Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. In most patients it is a sporadic tumor entity, less commonly it falls on the spectrum of Lynch syndrome, an autosomal dominant familial tumor syndrome. Localized UTUC with high-risk features as well as the metastatic disease scenario might require systemic therapy. Platinum-based combination chemotherapy is currently the recommended management option. However, the introduction of immune checkpoint inhibitors into the therapeutic armamentarium has led to a paradigm shift in treatment standards. Immunotherapy has been shown to be safe and effective in treating at least metastatic UTUC, although UTUC-specific high-level evidence is still lacking. Recent technological advances and noteworthy research efforts have greatly improved the general understanding of the biological landscape of UTUC. According to the main findings, UTUC represent a particular subtype of urothelial carcinoma frequently associated with activated FGFR3 signaling, a luminal-papillary phenotype and a T-cell-depleted microenvironment. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to ultimately result in better clinical outcomes. The aim of this review was to summarize the main currently available evidence on immune checkpoint inhibition and clinical genomics in UTUC.

Urethral Exposure of Mid-urethral Sling: Diagnosis, Management and Functional Outcomes.

OBJECTIVE: To identify symptoms leading to urethral mesh exposure diagnosis, describe the surgical management and evaluate post-operative functional and urodynamic outcomes. MATERIALS AND METHODS: Retrospective observational monocentric study of 15 patients treated by mid-urethral sling removal for urethral exposure, between December 2005 and February 2021, in a pelviperineology centre. RESULTS: Fifteen patients were included. The mean time to diagnosis of urethral exposure was 43 months. This diagnosis delay was caused by a non-specific symptomatology. Surgical management consisted of partial removal of the eroded mid-urethral sling fragment by vaginal approach in all cases, with low peri-operative morbidity. At 3 months follow-up, 87% of the patients had stress urinary incontinence vs 54% at 2 years. 13 patients had a urodynamic assessment after their mid-urethral sling removal, they all had sphincter insufficiency with a urethral closure pressure lower than 30 cm H2O. Nine patients underwent a second urinary incontinence management procedure, leading to 77% of complete remission and 23% of partial improvement. CONCLUSION: Clinical presentation of urethral erosion after mid-urethral sling is heterogeneous. Surgical management is complex; after a good preoperative evaluation, a two-step management strategy including minimally invasive mid-urethral sling removal and treatment of recurrent urinary incontinence leads to good results with 77% of patients cured. Sphincter insufficiency is one of the mechanisms that may explain the high rate of stress urinary incontinence after urethral mesh erosion surgery.

Impact of radiation therapy on artificial urinary sphincter implantation in male patients: A multicenter study.

AIMS: To evaluate the impact of an history of radiation therapy on the outcomes of artificial urinary sphincter (AUS) implantation in male patients. METHODS: The charts of all patients who underwent AUS implantation for stress urinary incontinence (SUI) after prostate surgery in thirteen centers between 2004 and 2020 were retrospectively reviewed. We excluded patients with neurogenic SUI. Continence rates and incidence of complications, revision and cuff erosion were evaluated. The outcomes in irradiated men were compared to those of non irradiated men. RESULTS: A total of 1277 patients who had an AUS met the inclusion criteria with a median age of 70 years, of which 437 had an history of prior radiotherapy. There was no difference in comorbidities. In irradiated patients, postoperative social continence, urethral atrophy and infection rates were respectively 75.6%, 2.4% and 9.5% and 76.8%, 5.4%, and 5.8% in nonirradiated men (respectively, p = 0.799, p = 0.128, p = 0.148). There were more urethral erosion in irradiated male patients. After a mean follow up of 36.8 months, the explantation free survival was poorer in irradiated patients (p = 0.001). CONCLUSION: These data suggest that pelvic radiotherapy before AUS adversely affect device survival with and increased greater occurrence of infection-erosion and therefore of explantation.

Early Efficacy and Safety Outcomes of Artificial Urinary Sphincter for Stress Urinary Incontinence Following Radical Prostatectomy or Benign Prostatic Obstruction Surgery: Results of a Large Multicentric Study.

BACKGROUND: Artificial urinary sphincter (AUS) is the gold standard for the management of moderate to severe stress urinary incontinence (SUI) in the male population. While outcomes of this device in postprostatectomy incontinence (PPI) are widely described, those obtained for incontinence after benign prostatic obstruction (BPO) surgery remains poorly explored. OBJECTIVE: To compare continence outcomes after AUS implantation in a PPI population with those obtained in men incontinent after BPO surgery. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of all cases of AUS implantation between 2005 and 2020 in 16 different French centers was conducted. Only patients with primary implantation whose indication was moderate to severe SUI after prostatectomy or BPO surgery were included (excluding those with a history of radiation therapy, brachytherapy, cystectomy, high-intensity focused ultrasound therapy, or neurogenic disease). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the rate of social continence (zero or one pad per day) at 3 mo. Complications were also noted within 90 d of implantation. RESULTS AND LIMITATIONS: A total of 417 patients were included in the PPI group and 50 in the BPO surgery group. Social continence rates at 3 mo were similar between the groups (79% vs 72%, p = 0.701). Complication rate was significantly higher in the BPO group (8% vs 18%, p = 0.044). The same was found for the Clavien-Dindo type 2 complication rate (20.6% vs 44.4%, p = 0.026). The retrospective nature and lack of precise definition of incontinence are the main limitations of this study. CONCLUSIONS: This multicentric study strengthens the position of AUS as gold standard for SUI after radical prostatectomy. Comparable efficacy results were found for incontinence after BPO surgery, with nevertheless a higher rate of complications. PATIENT SUMMARY: Artificial urinary sphincter represents the gold standard for the treatment of moderate to severe stress urinary incontinence. Efficacy results are comparable between postprostatectomy incontinence and incontinence after benign prostatic obstruction surgery.

Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study.

Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively (p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable (n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings.

Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer.

Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: "bladder cancer" OR "urothelial carcinoma", AND "neoadjuvant immunotherapy" OR "preoperative immunotherapy". We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer-4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.

Transcorporal vs. bulbar artificial urinary sphincter implantation in male patients with fragile urethra.

PURPOSE: To compare transcorporal vs bulbar artificial urinary sphincter (AUS) implantation in men with fragile urethra and to investigate the risk factors of AUS explantation in this population. METHODS: The charts of all male patients who had an AUS implantation between 2004 and 2020 in 16 centers were reviewed retrospectively. The primary endpoint was device explantation-free survival. Only patients with a fragile urethra were included in the present analysis. Fragile urethra was defined as a urethra carrying a high risk of cuff erosion because of prior radiotherapy and/or history of AUS explantation and/or history of urethral stricture surgery. The patients were divided in two groups according to the implantation site: bulbar vs transcorporal. RESULTS: 464 patients were included for analysis. 88 patients underwent a transcorporal AUS implantation and 376 underwent a bulbar AUS implantation. Explantation-free survival was similar in both groups (estimated 5-year explantation free survival rates 55.3% vs. 58.4%; p=0.98). In the subgroup of patients with a history of previous AUS explantation, transcorporal approach tended to bring longer explantation-free survival (2-year explantation-free survival: 61.9% vs. 58.2%; p=0.096). In multivariate analysis, the only risk factor of shorter explantation-free survival was the history of previous AUS explantation (HR=2.65; p=0.01). CONCLUSIONS: Transcorporal AUS implantation was not associated with longer explantation-free survival. History of previous AUS explantation was the only risk factor associated with shorter explantation-free survival and this subgroup of patients may be the only one to draw benefits of transcorporal AUS implantation.

Is it Worth Starting Sexual Rehabilitation Before Radical Prostatectomy? Results From a Systematic Review of the Literature.

Background and Purpose: Sexual dysfunction (SD) is a frequent side effect associated with radical prostatectomy (RP) for prostate cancer (PCa). Some studies have showed the benefit associated with preoperative sexual rehabilitation (prehabilitation) and Enhanced Recovery After Surgery (ERAS) for RP, but no clear clinical recommendations are available yet. Our aim was to conduct a systematic review on sexual prehabilitation prior to RP for patients with a localized PCa and analyze the impact on postoperative sexual health compared with the standard post-operative care. Methods: We performed a systematic review of the literature following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) recommendations. Results: Four randomized control trials and one retrospective comparative study were included in the analyses. Three of the five studies showed an improved EF recovery post-RP in the prehabilitation group compared to the standard of care represented by: higher International Index of Erectile Function 5 score (IIEF5) or IIEF score (p < 0.0001) and a higher percentage of patients reporting return of EF based on the Sexual Encounter Profile (SEP) (56 vs. 24%, p = 0.007). Self-confidence, therapeutic alliance, and adherence to treatment were stronger for patients with preoperative consultations (p < 0.05) and EF recovery was better in cases of a higher number of follow-up visits (OR 4-5 visits vs. 1:12.19, p = 0.002). Discussion: Despite heterogenous methods and high risks of bias in this systematic review, starting sexual rehabilitation prior to surgery seems to ensure better EF recovery. This prehabilitation should include information of both the patient and his or her partner, with a closer follow up and the use of a multimodal treatment approach that still remains to be defined and validated (oral medication, vacuum devices, pelvic floor muscle training, etc.).