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PurposeRadical cystectomy (RC) is currently the standard of care for non-metastatic muscle invasive bladder cancer. Few studies compare methods of cutaneous continent urinary diversion (CCUD) following RC. The objective was to compare perioperative morbidity and functional outcomes of CCUD using an ileal pouch with a Mitrofanoff efferent versus a Miami ileocolic pouch in patients undergoing cystectomy of pelvic exenteration for bladder cancer.MethodsThis retrospective two-centre study included all consecutive patients who underwent radical cystectomy or pelvic exenteration with CCUD for bladder cancer between 2001 and 2020 in two academic French hospitals with a median follow-up time of 5.4 years. Patients were divided into two groups according to the type of urinary diversion: Miami ileocolonic pouch (group A) and ileal pouch with Mitrofanoff/Monti principle (group B). Continence rate, ability to perform intermittent self-catheterisation, complications and health-related quality of life (HRQoL) measured by the bladder cancer index were evaluated.ResultsThirty-one patients were included. Continence was achieved in 11 out of 14 patients (79%) in group A versus 12 out of 17 patients (71%) in group B (P = 0.3). A significantly higher rate of cutaneous tube stenosis was reported in group B compared to group A (eight (47%) vs. one (7%) patient, respectively; P = 0.02). HRQoL outcomes were similar in both groups except less digestive discomfort observed in group A.ConclusionsWhen comparing the ileal pouch with Mitrofanoff/Monti’s principle with a Miami pouch, no significant differences were found regarding continence rate, ability to self-catheterise, long-term complication rate and overall patient satisfaction.

Background Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. Methods We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2 , SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time’s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. Results For Diagnosis : Using a logistic regression analysis with a model consisting of the 3 markers’ methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up : Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. Conclusions We showed that combined analysis of FGFR3 mutation and DNA methylation markers on urine can be a useful strategy in diagnosis, surveillance and for risk stratification of patients with NMIBC. These results provide the basis for a highly accurate noninvasive test for population screening and allowing to decrease the frequency of cystoscopy, an important feature for both patient quality of life improvement and care cost reduction.

Objectives To identify predictive factors and assess the impact on oncological outcomes of intravesical recurrence after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). Methods Using a national multicentric retrospective dataset, we identified all patients with UTUC who underwent a RNU between 1995 and 2010 ( n  = 482). Intravesical recurrence was tested as a prognostic factor for survival through univariable and multivariable Cox regression analysis. Results Overall, intravesical recurrence occurred in 169 patients (35 %) with a median age of 69.2 years (IQR: 60–76) and after a median follow-up of 39.5 months (IQR: 25–60). Actuarial intravesical recurrence-free survival estimates at 2 and 5 years after RNU were 72 and 45 %, respectively. On univariable analyses, previous history of bladder tumor, tumor multifocality, laparoscopic approach, pathological T-stage, presence of concomitant CIS and lymphovascular invasion were all associated with intravesical recurrence. On multivariable analysis, previous history of bladder cancer, tumor multifocality and laparoscopic approach remained independent predictors of intravesical recurrence. Existence of intravesical recurrence was not correlated with worst oncological outcomes in terms of disease recurrence ( p  = 0.075) and cancer-specific mortality ( p  = 0.06). Conclusions In the current study, intravesical recurrence occurred in 35 % of patients with UTUC after RNU. Previous history of bladder cancer, tumor multifocality, concomitant CIS and laparoscopic approach were independent predictors of intravesical recurrence. These findings are in line with recent published data and should be considered carefully to provide a definitive surveillance protocol regarding management of urothelial carcinomas regardless of the location of urothelial carcinomas in the whole urinary tract.

Purpose Prognostic impact of lymphadenectomy during radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UTUC) is controversial. Our aim was to assess the impact of lymph node status (LNS) on survival in patients treated by RNU. Methods In our multi-institutional, retrospective database, 714 patients with non-metastatic UTUC had undergone RNU between 1995 and 2010. LNS was tested as prognostic factor for survivals through univariate and multivariable Cox regression analysis. Results Median age was 70 years [interquartile range (IQR), 60–75] with median follow-up of 27 months (IQR, 10–50). Overall, lymphadenectomy was performed in 254 patients (35.5 %). Among these patients, 204 (80 %) had negative lymph nodes (pN0) and 50 (20 %) had positive lymph nodes (pN1/2). The 5-year cancer-specific survival (CSS) was 81 % [95 % confidence interval (CI), 73–88 %] for pN0 patients, 85 % (95 % CI, 80–90 %) for pNx patients and 47 % (95 % CI, 24–69 %) for pN1/2 patients ( p  < 0.001). Metastasis-free survival (MFS) and overall survival (OS) rates were significantly lower in pN1/2 patients than in pN0 and pNx patients ( p  < 0.05). On multivariable analysis, LNS did not appear as an independent prognostic factor for CSS, OS or MFS ( p  > 0.05). In case of lymph node involvement, extra-nodal extension was marginally associated with worse CSS (log rank p  = 0.07). The retrospective design was the main limitation. Conclusion LNS is helpful for survival stratification in patients treated with RNU for UTUC. However, LNS did not appear as an independent predictor of survival in this retrospective series and needs to be investigated in a large multicentre, prospective evaluation.

The HOXB13 gene is a member of the homeobox gene family, and prostate development depends on HOXB13 function. HOXB13 is a very sensitive and specific marker of prostate tissue and prostate cancer. When the origin of a tumor in a resection specimen or in biopsy material is unclear, it allows determining the prostate as the primary. Our aim was to determine whether HOXB13 has similar sensitivity for determining prostate origin of lymph node and bone metastases. We retrieved cases of lymph node and bone metastases of histologically confirmed prostate cancer (PCa) and selected lymph node metastases of urothelial carcinoma (UCa). A panel of antibodies against HOXB13, PSA, ERG, Androgen receptors, p504S, p63, GATA-3, CK7, and Uroplakin 2 and 3 was tested on these tissue samples. Two pathologists analysed and scored staining as either 0 (negative) or + (positive). The selected cohort consisted of 74 cases of lymph node and 15 of bone metastases of PCa and 15 of lymph node metastases of UCa. HOXB13 was expressed in 93 % of lymph node and in 33 % of bone metastases of PCa. All lymph node metastases of UCa were negative. Sensitivity of HOXB13 as a marker for prostate origin in lymph node metastases was 93 % and for bone metastases 33 %. Inter-observer variability in assessment of staining was good, as only two (1.9 %) of lymph node metastasis of PCa were discordant. HOXB13 is a useful marker for prostate origin when doubt exists regarding the site of the primary of a metastatic lesion. On bone metastases, HOXB13 immunohistochemistry performed less well, probably due to the use of tissue decalcification.

Key Points Lower urinary tract (LUT) symptoms are common in patients with multiple sclerosis; the exact symptoms vary in type and severity, and can evolve with progression of the disease The management of LUT dysfunction in these patients requires a consensual approach, with cooperation between different medical professionals, and should take into consideration possible progression of the disease Intermittent self-catheterization is essential for the management of patients with voiding symptoms, but might also have a role in management of those with storage symptoms Intradetrusor botulinum toxin A injections are a highly effective and minimally invasive treatment of storage dysfunctions Surgical options include augmentation cystoplasty, cutaneous continent diversion and ileal conduit surgery, and should be performed only after careful selection of patients Multiple sclerosis has a progressive course and, therefore, patients with multiple sclerosis who also have LUT symptoms require regular long-term follow-up monitoring Lower urinary tract symptoms (LUTS) occur in >80% of patients with multiple sclerosis, have a substantial negative effect upon patients' quality of life and require regular monitoring owing to the progressive nature of the underlying neurodegenerative disease. In this Review, the authors describe the optimal diagnosis, treatment and management of the wide variety LUTs that can occur in patients with multiple sclerosis. Lower urinary tract (LUT) dysfunction is common in patients with multiple sclerosis and is a major negative influence on the quality of life of these patients. The most commonly reported symptoms are those of the storage phase, of which detrusor overactivity is the most frequently reported urodynamic abnormality. The clinical evaluation of patients' LUT symptoms should include a bladder diary, uroflowmetry followed by measurement of post-void residual urine volume, urinalysis, ultrasonography, assessment of renal function, quality-of-life assessments and sometimes urodynamic investigations and/or cystoscopy. The management of these patients requires a multidisciplinary approach. Intermittent self-catheterization is the preferred option for management of incomplete bladder emptying and urinary retention. Antimuscarinics are the first-line treatment for patients with storage symptoms. If antimuscarinics are ineffective, or poorly tolerated, a range of other approaches, such as intradetrusor botulinum toxin A injections, tibial nerve stimulation and sacral neuromodulation are available, with varying levels of evidence in patients with multiple sclerosis. Surgical procedures should be performed only after careful selection of patients. Stress urinary incontinence owing to sphincter deficiency remains a therapeutic challenge, and is only managed surgically if conservative measures have failed. Multiple sclerosis has a progressive course, therefore, patients' LUT symptoms require regular, long-term follow-up monitoring.

PurposeThe aim of our study was to evaluate and compare the expression of different immunohistochemical markers in Bladder Carcinomas (BC) in patients with Neurogenic Bladder (NB) and Urinary Schistosomiasis (US) infection.Materials and methodsWe collected tissue samples from patients with Neurogenic Bladder and Bladder Carcinoma (NBC Group) and from patients with Urinary Schistosomiasis infection and Bladder Carcinoma (SBC Group). We compared to these two groups to control samples from resection from patients with Urinary Schistosomiasis without Bladder Carcinoma (US Group); we also investigate patients’ characteristics according to urothelial transitional cell carcinoma (TCC), and squamous cell carcinoma (SCC) histopathological differentiation. The expression of markers in all groups (CK7, CK14, CK20, FoxP3, GATA3, STAG2, CD3, CD8, Ki67, and P53) was analyzed using immunohistochemistry of tissue micro-array sections (TMA).ResultsOverall, 136 patients were included in the study (n = 72 in the NBC group, n = 33 in the SBC group, and n = 31 in the US group). In the TCC subgroup, the expression of CK7, CK14, CK20, and Ki67 was significantly higher compared to US controls (p 0.002; p < 0.001; p 0.036; p < 0.001). In the SCC subgroup, the expression of CK7, CK14, and CK20 was significantly higher compared to US controls (p 0.007; p < 0.001; p 0.005). Both in TCC and SCC subgroups, no difference in the expression of any tested markers was found comparing NBC and SBC groups. In US group, a significant higher expression of STAG2 was found compared to SCC subgroup (p 0.005).ConclusionBased on our results, the profile of immunohistochemical biomarkers’ expression in both NBC and SBC groups is similar.

PurposeTo assess the outcomes after artificial urinary sphincter (AUS) implantation in older women aged over 75 years.MethodsA monocentric retrospective study included all non-neurological women aged over 75 years suffering from stress urinary incontinence (SUI) due to intrinsic sphincter deficiency and undergoing an AUS placement between 1991 and 2015. Early postoperative complications were reported according to Clavien-Dindo classification. Continence, defined as no pad use, was assessed at the end of follow-up. Explantation, revision and deactivation rates of the AUS were reported. A Kaplan–Meier survival curve was generated to evaluate the survival rate of the device without revision or explantation.ResultsAmong 393 AUS implantations, a total of 45 patients, median age 77 years (IQR 75–79), were included. Twenty-six early postoperative complications occurred in 18 patients (40%) patients. All were minor Clavien grades (I-II) except one (grade IVa). Median follow-up was 36 months (IQR 16–96). Overall, 32 women (71.1%) still had their AUS in place at the end of the follow-up, without revision or explantation. The AUS was definitively removed in four (8.9%). The AUS required revisions in nine (20%) women. The 5- and 10-year survival rates of the device without revision or explantation were 78 and 50%, respectively. Three patients (6.7%) had their AUS deactivated. At last follow-up, in an intention-to-treat analysis, the continence rate was 68.9%.ConclusionIn women aged over 75-years-old, suffering from SUI, the AUS provides satisfactory functional results comparable to the general population.

Purpose Nerve-sparing radical prostatectomy (NSRP) is based on anatomical considerations that are still controversial. The aim of this study is to define and describe the anatomy of the fascias surrounding the prostate in a histoembryologic model and during open and laparoscopic approaches to assess their importance in surgical practice. Methods An anatomical dissection of three fresh cadavers was conducted to reproduce an open approach. Complementary data under laparoscopic conditions were obtained from images captured from the video feed during a laparoscopic NSRP performed via a transperitoneal approach. A histological study of one fresh 25-week human male fetus, obtained following miscarriage, was also conducted to document the embryologic development of the identified fascias. Results Three fascias surrounding the prostate can clearly be individualized both in histologic and clinical conditions. The endopelvic fascia (EF), the prostatic fascia (PF) and the Denonvilliers’ fascia (DF) recover the prostate gland and structure the periprostatic environment. Neurovascular bundles are situated in a triangle formed by PF, EF and DF. Interfascial dissection (between EF and PF) allows nerve-sparing surgery. Conclusion When performing radical prostatectomy, it is mandatory to locate EF, PF and DF precisely to respect the neurovascular bundles. Nevertheless, cancer extension and anatomic variations can lead to more extensive procedures.