Diffusion-Weighted Magnetic Resonance Imaging: A New Tool for the Diagnosis of Bladder Pain Syndrome/Interstitial Cystitis.

OBJECTIVES: To determine whether diffusion-weighted magnetic resonance imaging (DWMRI), a noninvasive procedure, can contribute to the diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC). METHODS: The pelvic DWMRI of patients with chronic pelvic pain syndrome was selected between January 2012 and June 2017. A radiologist analyzed the bladder wall signal; he was blinded to the patients' clinical data. According to the 2008 European Society for the Study of Bladder Pain Syndrome/Interstitial Cystitis criteria, 2 groups of patients were determined: BPS/IC and no BPS/IC. The association between BPS/IC and the wall signal intensity was compared. RESULTS: In the 106 patients included, 82 had criteria for BPS/IC and 24 did not. A significant difference in the distribution of the signal was found between the 2 groups (p = 0.01). High signal intensity of the bladder wall was related to the presence of a BPS/IC with a sensitivity of 28% and a specificity of 88%. No signal intensity of the bladder wall was related to the absence of a BPS/IC with a sensitivity of 96% and a specificity of 29%. CONCLUSIONS: In -DWMRI, high bladder wall signal intensity helps to affirm a BPS/IC, whereas the absence of signal helps to exclude the diagnosis. Further studies are needed to confirm these preliminary results.

Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer.

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.

The Diagnostic and Prognostic Performance of Urinary FGFR3 Mutation Analysis in Bladder Cancer Surveillance: A Prospective Multicenter Study.

OBJECTIVE: To assess the diagnostic and prognostic performance of a noninvasive FGFR3 mutation analysis. After transurethral resection (TUR) of noninvasive bladder transitional cell carcinoma (B-TCC), recurrence occurs in 70% of patients, thus justifying cystoscopic surveillance. MATERIALS AND METHODS: A prospective multicenter study was carried out with a 2-year follow-up of patients with superficial B-TCC. Urine samples were collected before TUR and then before each cystoscopy during follow-up. Screening for the most prevalent FGFR3 mutations was done using urinary cells. The prognostic significance of an FGFR3 mutation at the time of the initial diagnosis was determined. The performance of the test in diagnosing and/or predicting recurrence during follow-up was assessed by calculating sensitivity and specificity. RESULTS: Of 191 patients studied, 74 (39%) had a positive analysis before TUR (FGFR3 mutation group). The presence of an FGFR3 mutation at the time of diagnosis was associated with a shorter time to recurrence (P = .02). During follow-up, 68 patients from the FGFR3 mutation group were evaluated. FGFR3 mutation analysis showed a sensitivity of 0.73 and a specificity of 0.87 when compared with the results of cystoscopy. A positive urine test was predictive of recurrence either at the time of the positive result or later during the 2-year follow-up, with a sensitivity of 0.70 and a specificity of 0.87. CONCLUSION: Among patients with an FGFR3 mutation in the initial tumor, a noninvasive urine test during follow-up can be valuable in diagnosing or predicting subsequent recurrence.

Intrasphincteric injections of autologous muscular cells in women with refractory stress urinary incontinence: a prospective study.

INTRODUCTION AND HYPOTHESIS: Cell therapy for stress urinary incontinence (SUI) management has been experienced with encouraging results. METHODS: We conducted an open prospective study on 12 women presenting severe SUI with fixed urethra, after previous failed surgical management. Patients underwent intrasphincteric injections of autologous progenitor muscular cells isolated from a biopsy of deltoid muscle. Primary endpoint focused on safety (measurement of Q(max) variation after 3 months). Secondary endpoints assessed side effects and efficacy. RESULTS: No variation was diagnosed on Q(max) measurements. Efficacy data show that three of 12 patients are dry at 12 months, seven other patients are improved on pad test but not on voiding diary, and two patients were slightly worsened by the procedure. Quality of life was improved in half of patients. CONCLUSIONS: Cell therapy for severe multioperated cases of SUI is a mini-invasive, feasible, and safe procedure that can improve urinary condition in as a second line therapy.

Mid-term evaluation of the transobturator male sling for post-prostatectomy incontinence: focus on prognostic factors.

OBJECTIVE: • To assess clinical outcomes at mid-term follow-up and determine preoperative factors associated with the failure of the Advance(TM) male sling for post-prostatectomy incontinence (PPI). PATIENTS AND METHODS: • A prospective evaluation was conducted of 136 consecutive patients implanted with the Advance(TM) male sling for mild to moderate stress urinary incontinence after prostatectomy. • Patients were preoperatively evaluated using medical history, ASA score, urodynamics, 24-h pad test and pad usage. • The clinical outcome was evaluated according to pad use and the Patient Global Impression of Improvement scale and by assessment of side effects. 'Cure' was defined as no pad usage and 'improvement' as a decrease in pad use by >50%. • Factors related to functional outcome were studied by univariate and multivariate analysis. RESULTS: • After a mean ± SD (range) follow-up of 21 ± 6 (12-36) months, 62% of patients were cured, 16% improved and 22% not improved. • Failure (no cure or improvement) was associated with previous urethral stricture surgery (P= 0.013) and a 24-h pad-test >200 g/day (P= 0.026), and there was a trend for an association with previous radiation therapy (P= 0.053). • Age, learning curve and type of prostatectomy did not affect the results. • Immediate postoperative complications were limited to two cases of dysuria, one case of perineal haematoma and two cases of perineal paresthesia. During follow-up, 10% of patients had perineal pain and 14% of patients had mild dysuria. None required surgical management. CONCLUSION: • The results of the present study, with a follow-up of up to 3 years, confirm that the Advance(TM) male sling is an efficient treatment for PPI. However, particular attention should be given to the preoperative data associated with failure.

The AdVance transobturator male sling for postprostatectomy incontinence: clinical results of a prospective evaluation after a minimum follow-up of 6 months.

BACKGROUND: Transobturator male slings have been proposed to manage stress urinary incontinence (SUI) after prostatic surgery, but data are still lacking. OBJECTIVE: To determine the safety and prospectively evaluate the clinical outcome after management of SUI after prostatic surgery by placement of a transobturator male sling. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective evaluation on 102 patients treated in a single center between 2007 and 2009 for mild to moderate SUI following prostatic surgery. INTERVENTIONS: Placement of a suburethral transobturator sling and clinical follow-up. MEASUREMENTS: Patients were evaluated by medical history, preoperative urodynamics, maximum flow rate measurement, 24-h pad test, and daily pad use. During follow-up, data on patients' pad use, complications, and answers to the Patient Global Impression of Improvement (PGI-I) questionnaire were collected. Cure was defined as no pad usage or one pad for security reasons and improvement as reduction of pads≥50%. Median follow-up was 13 mo (range: 6-26). RESULTS AND LIMITATIONS: Most patients (95%) presented post-radical prostatectomy incontinence (PRPI). Hospital stay was 2 d in 97 cases, and all patients were catheterized for 24h except two (48 h). Of 102 patients, 64 were cured, 18 were improved, and 20 were not improved. According to the PGI-I questionnaire, 85%, 11%, and 4% of patients described a respectively better, unchanged, and worse urinary tract condition, respectively. Previous radiation was associated with higher rate of failure (p=0.039). Neither severe complication nor postoperative urinary obstruction was noted during follow-up. CONCLUSIONS: Placement of a transobturator sling is a safe and effective procedure, giving durable results after >1 yr of follow-up. Further evaluation and high-quality controlled, randomized studies are needed to assess long-term efficacy and precise indications of this procedure for post-prostatic-surgery SUI management.

Objective and subjective cure rates after trans-obturator tape (OBTAPE) treatment of female urinary incontinence.

OBJECTIVE(S): To evaluate the safety and efficacy of a thermally bonded nonwoven polypropylene mesh in a transobturator suburethral tape procedure (OBTAPE), Mentor-Porges, Le Plessis Robinson, France) for women with stress urinary incontinence. METHODS: Between January 2003 and January 2005, 129 consecutive women (mean age 57.2 years) underwent OBTAPE) in two academic centers. All the patients had stress urinary incontinence preoperatively. Detrusor instability was ruled out by cystometry. The women were evaluated 1, 6 and 12 months postoperatively. The objective cure rate was evaluated by clinical examination and the subjective cure rate was assessed using the KHQ and BFLUTS questionnaire. RESULTS: Mean follow-up was 17.2+/-4.7 months (range 4 to 28 months). The objective and subjective cure rates were respectively 89.9% and 77.5%. Most of the patients received general anesthesia (85.3%). Urinary retention was observed in two women (1.5%), necessitating tape adjustment. Voiding difficulties were observed in 7 cases (5.4%) necessitating intermittent self-catheterization for 4.2+/-2.4 days (range 1 to 7 days). Seven patients developed vaginal erosion (one with vaginal extrusion, and two with an obturator abscess). Complete mesh removal was necessary in 6 patients, four of whom had recurrent stress urinary incontinence. CONCLUSIONS: Our results suggest that the OBTAPE) is an effective treatment for women with stress urinary incontinence. However, vaginal mesh erosion occurred in 6.2% of women, and this implies the need for careful follow-up.

A French multicenter clinical trial of SPARC for stress urinary incontinence.

OBJECTIVE: To evaluate the safety and efficacy of the SPARC procedure in women with genuine stress urinary incontinence. METHODS: We conducted a prospective multicenter trial of a suprapubic approach to suburethral polypropylene (SPARC) taping for the treatment of genuine stress urinary incontinence. Between June 2001 and June 2002, 104 consecutive women (mean age 58.7 years) underwent SPARC in three centers. All the women had urethral hypermobility preoperatively. Detrusor instability was ruled out by cystometry. The women were evaluated 1, 3, 6 and 12 months postoperatively. The objective cure rate was evaluated by clinical and urodynamic examination, and the subjective cure rate was assessed using the Kings and Bristol questionnaire. RESULTS: The mean follow-up time was 11.9+/-1.9 months (range 8 to 20 months). The mean operating time was 30 min (25-50 min). Most of the patients received general anesthesia (48%). The overall complication rate was 44.2% (46/104). The perioperative complication rate was 10.5%, including 11 bladder injuries. A significant difference in the bladder injury rate was observed between women with and without previous incontinence surgery (respectively 4/11, 36.3% versus 7/93, 7.5%; p<0.001). No hemorrhaging occurred. The early postoperative complication rate was 22.1%. The main complication was voiding disorders (11 patients), which necessitated intermittent self-catheterization for less than 15 days (1.3+/-1.1 days, range 1 to 10 days). The late postoperative complication rate was 11.5%, including de novo urge symptoms in 12 women. The objective cure rate was 90.4%. No difference was found between patients with genuine stress incontinence and those with mixed incontinence. The subjective cure rate was 72%. The objective and subjective cure rates differed significantly (p<0.05). The subjective cure rate among patients with de novo urge symptoms was 58%. CONCLUSION: The SPARC procedure is a safe and effective treatment for women with stress urinary incontinence, despite a high incidence of de novo urge symptoms.

Results of the tension-free vaginal tape technique in the elderly.

OBJECTIVES: To assess the results of the Tension-Free Vaginal Tape (TVT) technique for the treatment of stress urinary incontinence (SUI) in the elderly. PATIENTS AND METHODS: Between March 1998 and February 2001, 76 consecutive women more than 70 years old (median 76) and presenting with SUI were operated with the TVT technique. 28.9% (22/76) of the patients had previous surgery for SUI. 31% (24/76) of the patients had an overactive bladder and 4 patients had detrusor instability controlled by anticholinergic therapy. All patients had preoperative multichanel urodynamic evaluation. RESULTS: No serious complication was noted intra- or postoperatively. At a mean follow up of 24.6 months (range 16-49 months), 67% of the patients were cured (51/76). Among the failures, 10 patients (13.7%) had persistent SUI, 14 patients (18.4%) had urge incontinence and 2 patients were lost to follow up. De novo urgency without incontinence was noticed in 21% of the patients but preoperative urgency symptoms were cured in 46% of the patients. Overall 82% of the patients were satisfied with the result of the surgery, 14% considered the result as incomplete and 4% considered they were worsened by surgery. CONCLUSION: The TVT procedure is safe and efficient to treat SUI in the elderly population even if the rate of de novo urgency appeared to be significant.

Complications of urethral sling procedures.

PURPOSE OF REVIEW: To review the current literature on complications of suburethral slings used to treat stress urinary incontinence in the female. RECENT FINDINGS: The surgical treatment of female urinary incontinence has changed considerably since the development of the tension-free vaginal tape procedure, introduced by Ulmsten in 1995. As the follow-up for the first studies is now more than 5 years, the 'long-term' results of the technique can be evaluated. Furthermore, now that the learning phase has been completed and the technique can be considered to be well mastered, it is interesting to review the complications inherent in this technique, their frequency, including those rarer complications that are sometimes associated with severe morbidity, and to consider the ways in which these complications can be prevented or treated. The development of the tension-free vaginal tape procedure has not prevented the development of other types of suburethral sling, but on the contrary, has promoted the development of these alternatives by the use of various sling insertion techniques, and especially various types of materials. There has even been a renewed interest in materials that have been known for a long time (heterologous and autologous materials) in some recent papers, and new synthetic suburethral slings have been proposed with the objectives of combining low morbidity, safety and efficacy. SUMMARY: Monofilament polypropylene meshes can be used safely to perform suburethral slings and seems to be the most suitable material in this indication according to the existing literature.

Prospective evaluation of genetic abnormalities and telomerase expression in exfoliated urinary cells for bladder cancer detection.

PURPOSE: To evaluate alternative procedures to cytoscopic examination we prospectively compared noninvasive procedures for detecting bladder cancer namely cytology, loss of heterozygosity (LOH), microsatellite instability and human telomerase catalytic subunit reverse transcriptase (hTERT) messenger (m) RNA detection. MATERIALS AND METHODS: Specificity and cutoff values were established in the blood and urine sediment of 50 controls. Sensitivity was analyzed in the urine and tissue samples of 50 patients with bladder cancer. The diagnosis was established by cystoscopic and histological examination. Genomic alterations were studied using a panel of 24 microsatellite markers to detect LOH events, while 3 additional mononucleotide repeats were analyzed for microsatellite instability detection. Telomerase expression was detected in urinary cells by nested RT-polymerase chain reaction amplification of hTERT mRNA. All techniques were compared by cytological examination. RESULTS: Sensitivity and specificity were 31% and 100% for cytological testing, 96% and 100% for LOH, and 75% and 69% for RT-polymerase chain reaction of hTERT, respectively. No alteration was detected on microsatellite instability analysis in urine or tumor tissue cells. Using only the 5 markers most strongly associated with bladder cancer selected by logistic regression analysis, namely ABL1, IFNa, D9S12, MJD58 and D18S364, LOH test sensitivity slightly decreased to 90%. CONCLUSIONS: Urinary LOH analysis was the most sensitive and specific method for bladder cancer detection and it appeared less dependent on urine sediment quality. The logistic regression score may be an interesting complement to cystoscopy. The specificity of hTERT mRNA detection was incomplete since false-positives were observed in 31% of cases. Absent microsatellite instability in our cohort showed that these genomic alterations are not present at the early step of bladder cancer.