Stable Bladder Research Articles

Reduction of Overactive Bladder Medications in Spinal Cord Injury With Self-Administered Neuromodulation; a Randomized Trial.

To evaluate if self-administered bladder neuromodulation with transcutaneous tibial nerve stimulation can safely replace overactive bladder medications in people with spinal cord injury. We performed a 3-month, randomized, investigator-blinded, tibial nerve stimulation vs sham-control trial in adults with spinal cord injury and neurogenic bladder performing intermittent catheterization and taking overactive bladder medications. The primary outcome was a reduction in bladder medications while maintaining stable bladder symptoms and quality of life based on pre-post Neurogenic Bladder Symptom Score and the Incontinence-QOL questionnaire, respectively. Secondary outcomes included changes in pre-post cystometrogram, 2-day voiding diaries, and an anticholinergic medication side effect survey. Fifty people consented to the study, with 42 completing the trial. No dropouts were due to stimulation issues. All baseline demographics and surveys were comparable at baseline. Cystometrogram parameters were also comparable at baseline, except the stimulation group had a higher proportion of loss of bladder compliance compared to the control group. At the end of the trial, a significantly greater percentage of the tibial nerve stimulation group were able to reduce medications (95% v 68%), by a 26.2% difference in medication reduction (95% confidence interval 1.17%-51.2%). Function and quality of life surveys and cystometrograms at the end of the trial were alike between groups. Transcutaneous tibial nerve stimulation satisfaction surveys and adherence to protocol were high. In people with chronic spinal cord injury performing intermittent catheterization, transcutaneous tibial nerve stimulation can be an option to reduce or replace overactive bladder medications.

PD23-04 URINARY PROTEINS IN THE DIAGNOSIS OF MIXED INTRINSIC SPHINCTER DEFICIENCY AND DETRUSOR OVERACTIVITY IN FEMALE PATIENTS WITH STRESS URINARY INCONTINENCE?

You have accessJournal of UrologyCME1 Apr 2023PD23-04 URINARY PROTEINS IN THE DIAGNOSIS OF MIXED INTRINSIC SPHINCTER DEFICIENCY AND DETRUSOR OVERACTIVITY IN FEMALE PATIENTS WITH STRESS URINARY INCONTINENCE? Wei-Hsin Chen, Yuan-Hong Jiang, and Hann-Chorng Kuo Wei-Hsin ChenWei-Hsin Chen More articles by this author , Yuan-Hong JiangYuan-Hong Jiang More articles by this author , and Hann-Chorng KuoHann-Chorng Kuo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003296.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To investigate urinary biomarkers in women with stress urinary incontinence (SUI). METHODS: We retrospectively enrolled 93 female patients with SUI. The patients were categorized into the following three groups based on video-urodynamic findings: intrinsic sphincter deficiency (ISD) and detrusor overactivity (DO), ISD and hypersensitive bladder (HSB), and ISD and stable bladder (controls) groups. RESULTS: The mean age of the cohort was 60.8±10.7 (36–83) years (Table 1). Thirty-one (33.3%), 28 (30.1%), and 34 (36.6%) patients were included in the ISD and DO, ISD and HSB, and control groups, respectively. The ISD and DO group had significantly increased 8-isoprostane (mean, 33.285 vs. 10.795 pg/mL) and 8-hydroxy-2-deoxyguanosine (8-OHdG; mean, 28.912 vs. 17.416 ng/mL) and decreased interleukin (IL)-2 (mean, 0.433 vs. 0.638 pg/mL), vascular endothelial growth factor (mean, 5.506 vs. 8.989 pg/mL), and neural growth factor (mean, 0.175 vs. 0.235 pg/mL) levels than the controls (Figure 1). The analytes from controls were moderately diagnostic of DO, except for 8-isoprostane [area under the curve (AUC) >0.7]. Voided volume was highly diagnostic of DO from either controls or non-DO patients (AUC 0.750 and 0.915 respectively). The proposed prediction model with voided volume, 8-OHdG, and 8-isoprostane (cutoff values of 384 ml, 35 ng/mL, and 37 pg/mL, respectively) had an accuracy of 81.72% (sensitivity, 67.74%; specificity, 88.71%; positive predictive value, 75.00%; and negative predictive value, 84.62%). CONCLUSIONS: Combined with voided volume, urinary oxidative stress biomarkers have the potential to be used to identify urodynamic DO in patients with SUI. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e671 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei-Hsin Chen More articles by this author Yuan-Hong Jiang More articles by this author Hann-Chorng Kuo More articles by this author Expand All Advertisement PDF downloadLoading ...

Transurethral Incision of the Bladder Neck with or without Additional Procedure Resumes Spontaneous Voiding in Female Voiding Dysfunction-A Long-Term Retrospective Follow-Up.

This study evaluated the long-term effectiveness of transurethral incision of the bladder neck (TUI-BN) with or without an additional procedure for female voiding dysfunction. Women with voiding difficulty who underwent TUI-BN in the last 12 years were included. All patients underwent a videourodynamics study (VUDS) at baseline and after TUI-BN. A successful outcome was defined as having a voiding efficiency (VE) increase by ≥50% after treatment. Patients with insufficient improvement were chosen for repeated TUI-BN, urethral onabotulinumtoxinA injection, or transurethral external sphincter incision (TUI-ES). The current voiding status, surgical complications, and additional surgeries were evaluated. A total of 102 women with VUDS evidence of a narrow bladder neck during voiding were enrolled. The long-term success rate of the first TUI-BN was 29.4% (30/102) and increased to 66.7% (34/51) after combining TUI-BN and an additional procedure. The overall long-term success rates were 74.6% in women with detrusor underactivity (DU), 52.0% in detrusor overactivity and low contractility, 50.0% in bladder neck obstruction, 20.0% in hypersensitive bladder, and 75% in stable bladder (p = 0.022). Patients with a lower maximum flow rate (Qmax), (p = 0.002), lower voided volume (p < 0.001), lower corrected Qmax (p < 0.001), lower ladder contractility index (p = 0.003), lower voiding efficiency (p < 0.001), but larger post-void residual volume (p < 0.001) had a satisfactory surgical outcome. Spontaneous voiding was achieved in 66 (64.7%) patients, de novo urinary incontinence in 21 (20.6%), and vesicovaginal fistula in 4 (3.9%), all were repaired. TUI-BN alone or in combination with an additional procedure was safe, effective, and durable in patients with DU to resume spontaneous voiding.

Urinary Oxidative Stress Biomarkers in the Diagnosis of Detrusor Overactivity in Female Patients with Stress Urinary Incontinence.

Ninety-three women with urodynamic stress incontinence (USI) and a mean age of 60.8 ± 10.7 (36-83) years were retrospectively enrolled. According to their VUDS, 31 (33%) were grouped into USI and detrusor overactivity (DO), 28 (30.1%) were grouped into USI and hypersensitive bladder (HSB), and 34 (36.6%) were controls (USI and stable bladder). The USI and DO group had significantly increased 8-isoprostane (mean, 33.3 vs. 10.8 pg/mL) and 8-hydroxy-2-deoxyguanosine (8-OHdG; mean, 28.9 vs. 17.4 ng/mL) and decreased interleukin (IL)-2 (mean, 0.433 vs. 0.638 pg/mL), vascular endothelial growth factor (mean, 5.51 vs. 8.99 pg/mL), and nerve growth factor (mean, 0.175 vs. 0.235 pg/mL) levels compared to controls. Oxidative stress biomarkers were moderately diagnostic of DO from controls, especially 8-isoprostane (area under the curve (AUC) > 0.7). Voided volume was highly diagnostic of DO from either controls or non-DO patients (AUC 0.750 and 0.915, respectively). The proposed prediction model with voided volume, 8-OHdG, and 8-isoprostane (cutoff values 384 mL, 35 ng/mL, and 37 pg/mL, respectively) had an accuracy of 81.7% (sensitivity, 67.7%; specificity, 88.7%; positive predictive value, 75.0%; negative predictive value, 84.6%). Combined with voided volume, urinary oxidative stress biomarkers have the potential to be used to identify urodynamic DO in patients with USI.

356 An Unfortunate Case of Spinal Injury and Bladder Dysfunction During the Covid-19 Pandemic

Abstract There is no doubt that COVID-19 has had a profound impact on every medical and surgical speciality. In the height of the pandemic many non-emergency services were shut down, including dental services, with unexpected consequences. We present a case which highlights the unexpected and indirect consequences of a national lockdown on a Urology patient and discuss learning points. A 54-year-old male, previously fit and well suffered with a small dental abscess, media outlets were reporting that dental surgeries were closed, and he therefore attempted to drain the abscess himself. The infection spread to his epidural space, causing compression via a collection at L2 and consequently spinal cord injury. This was managed with urgent lumbar decompression and antibiotics. A specialist functional urology team were involved after his transfer to the tertiary spinal unit 3 months after his first presentation. He was catheterised but suffered with recurrent catheter blockages. Video urodynamics demonstrated a stable bladder with a low-pressure leak point, managed with urethral catheterisation. A repeat video urodynamics demonstrated a loss of compliance and stress incontinence. Unclear as to whether he would regain function rehabilitation techniques are currently being attempted prior for definitive operative management with an artificial sphincter. This case highlights the indirect impact of COVID-19 on UK urology services, and this has not been widely reported.

Incidence trends in bladder and lung cancers between Denmark, Finland and Sweden may implicate oral tobacco (snuff/snus) as a possible risk factor

BackgroundThe dominant risk factor for urinary bladder cancer has been cigarette smoking, but, as smoking prevalence is decreasing in many populations, other risk factors may become uncovered. Such new risk factors could be responsible for halting the declining incidence of bladder cancer. We hypothesize that snuff use by Swedish men may increase the rate for bladder cancer, as snuff contains carcinogenic nitrosamines.MethodsWe carried out an ecological study by comparing incidence trends in lung and bladder cancers between Danish, Finnish and Swedish men in order to test if the Swedish bladder cancer rate deviates from the Danish and Finnish ones. We used the NORDCAN database for cancer data from 1960 through 2016 to test the hypothesis.ResultsIn the three countries, the incidence of lung cancer started to decrease after a peak incidence, and this was later followed by declining incidence in bladder cancer in Denmark from 1990 to 2016 by 14.3%, in Finland by 8.3% but not in Sweden (the decline of 1.4% was not significant). The difference in trends can be partly explained by the increasing incidence in Swedish men aged 70 or more years. Sweden differs from the two other countries by low male smoking prevalence but increasing use of snuff recorded by various surveys.ConclusionThe stable bladder cancer trend for Swedish men was opposite to the declining trends in Denmark, Finland and globally. We suggest that this unusual finding may be related to the increasing use of snuff by Swedish men. Average users of snuff are exposed to at least 3 times higher levels of carcinogenic tobacco-specific nitrosamines than a smoker of one daily pack of cigarettes.

Effects of oxybutynin in children with posterior urethral valves post fulguration: Report in a select cohort of children

Objectives:Posterior urethral valves (PUV) is the commonest obstructive uropathy with varied consequences. Though valve fulguration is the treatment of choice, appropriate bladder management modifies outcome and includes rational use of anticholinergics. Here, we aim to evaluate the effects of oxybutynin on the bladder and urinary tract morphology and function. Concurrently, we document adverse effects encountered, patient compliance, and medication adherence.Methods:A retrospective study of children below 5 years of age (2012–2017) post fulguration and on oxybutynin for at least 6 months. Patient demographics, clinical features, renal ultrasound, micturating cystourethrogram, dimercaptosuccinic acid scan, adverse effects, and pill count for medication adherence were collated.Results:48 children below the age of 5 years were included, and 12 were excluded either due to the presence of concomitant problems or were not on oxybutynin. Of the 36, four were lost to follow-up and one had died due to an unrelated condition. Thus, a total of 31 children were analyzed. At follow-up, 28/31 patients were asymptomatic, two had daytime incontinence, and one had recurrent urinary tract infection. All patients except one have preserved renal function tests. On ultrasonography, hydroureteronephrosis worsened in only 1/25 children and two showed significant post void residues. The resolution of vesicoureteral reflux was noted in almost 50%. 4/31 renal units had progressive scars. Only two parents defaulted medication. Urodynamic study done in half of these children showed stable bladder pressures except in two.Conclusion:Oxybutynin therapy following adequate valve fulguration aids upper tracts preservation by stabilizing deranged bladder dynamics. The medication is well tolerated with minimal or no side effects.

S1621 Bladder in the Colon: A Rare Case of Hematochezia

INTRODUCTION: Colorectal cancer is the most common malignancy in the GI tract. Metastatic lesion to the colon are uncommon, accounting for only 1% of all colorectal neoplasms. The most common form of metastatic spread to the bowel is through peritoneal spreading. Hematogenous and lymphatic spread to the colon is reported in breast carcinoma, lung carcinoma, and melanoma. We present a rare cause of colorectal neoplasm. CASE DESCRIPTION/METHODS: A 65yo male with a history of ESRD and urothelial carcinoma presenting with hematochezia for 2 day. Symptoms began abruptly and were painless. He reported dizziness. He denied prior history of similar episodes. Patient denied melena, constipation, or any other GI symptoms. He is not on blood thinners. Of note, patient has chronic hematuria related to his malignancy, requiring blood transfusions. His most recent outpatient labs 1 week prior revealed a hemoglobin of 8.6g/dL. Patient is on neoadjuvant pembrolizumab. Surgical history included a prior bladder biopsy. He had no reported of prior colonoscopy. He is a former smoker with no other toxic habits and no pertinent family history. On admission, HR 110, BP 85/50, and was afebrile, saturating 100% on room air. Exam was remarkable for conjunctival pallor. Rectal exam revealed red blood without notable masses or lesions. Labs were significant for a hemoglobin of 7.1g/dL, creatinine of 3.5 and BUN of 42. The remainder of his CBC and CMP were unremarkable. He was transfused 1unit packed red blood cells and given IV fluids with improvement in his BP. He underwent a colonoscopy which revealed a 4 × 3 cm cecal mass with an adherent clot. The mass was injected with epinephrine, clot was successfully removed, and the mass was biopsied. Additionally, there was blood throughout the colon, and non-bleeding diverticuli in the transverse and sigmoid colon. Pathology revealed high grade carcinoma consistent with metastatic urothelial carcinoma, morphologically similar to his prior TURP specimens. Patient had a follow-up CT C/A/P that showed no other notable metastatic disease with stable bladder mass noted on a surveillance CT scan 3 months prior. Patient went for a right hemicolectomy for further management. Patient had oncologic followup for treatment. DISCUSSION: Although colon malignancy is common, metastatic urothelial cancer isolated in the colon is rare. Managing such cases is difficult as literature is unavailable. Further research is needed to understand methods of metastasis, predicting outcomes, and managing patients.Figure 1.: Cecal mass with notable adherent clot.Figure 2.: Cecal mass status post epinephrine injection and clot removal.

The significance of pelvic floor support on the pelvic floor muscle functions of women with lower urinary tract symptoms

ObjectiveTo explore the significance of pelvic organ prolapse (POP) on pelvic floor muscle (PFM) function among women with lower urinary tract symptoms (LUTS). Materials and methodsFour-dimensional ultrasound data of 577 women with LUTS were retrospectively analyzed. The bladder neck and genital hiatus were assessed during resting, coughing, and squeezing. The bladder neck location, genitohiatal size, and genitohiatal location were evaluated with bladder neck distance (BNd) and bladder neck angle (BNa), genitohiatal dimension (GHd) and genitohiatal area (GHAR), and genitohiatal angle (GHa), respectively. ResultsCompared with women without POP (n = 306), women with POP (n = 271) exhibited higher rates of levator complete avulsion (6.5% vs. 40.2%, P < 0.001), shorter BNd (2.84 ± 1.56 cm vs. 2.45 ± 0.45 cm, P = 0.018), larger BNa (92 ± 15° vs. 101 ± 21°, P < 0.001), longer GHd (5.25 ± 0.72 cm vs. 5.60 ± 0.87 cm, P < 0.001), larger GHa (141 ± 10° vs. 145 ± 9°, P = 0.004), and larger GHAR (20.0 ± 4.7 cm2 vs. 24.2 ± 5.6 cm2, P < 0.001) during resting. Fewer women with POP were able to maintain stable bladder neck location (79.5% vs. 65.5%, P < 0.001), genitohiatal size (60.7% vs. 51.9%, P = 0.042), and genitohiatal location (61.6% vs. 52.8%, P = 0.044) following coughing. Fewer women with POP were capable of squeezing (77.8% vs. 58.3%, P < 0.001). ConclusionAmong women with LUTS, the presence of POP is associated with weaker resting, involuntary, and voluntary PFM functions.

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a randomised controlled trial

Study designRandomised double-blind factorial-design placebo-controlled trial.ObjectiveUrinary tract infections (UTIs) are common in people with spinal cord injury (SCI). UTIs are increasingly difficult to treat due to emergence of multi-resistant organisms. Probiotics are efficacious in preventing UTIs in post-menopausal women. We aimed to determine whether probiotic therapy with Lactobacillus reuteri RC-14+Lactobacillus GR-1 (RC14-GR1) and/or Lactobacillus rhamnosus GG+Bifidobacterium BB-12 (LGG-BB12) are effective in preventing UTI in people with SCI.SettingSpinal units in New South Wales, Australia with their rural affiliations.MethodsWe recruited 207 eligible participants with SCI and stable neurogenic bladder management. They were randomised to one of four arms: RC14-GR1+LGG-BB12, RC14-GR1+placebo, LGG-BB12+ placebo or double placebos for 6 months. Randomisation was stratified by bladder management type and inpatient or outpatient status. The primary outcome was time to occurrence of symptomatic UTI.ResultsAnalysis was based on intention to treat. Participants randomised to RC14-GR1 had a similar risk of UTI as those not on RC14-GR1 (HR 0.67; 95% CI: 0.39–1.18; P = 0.17) after allowing for pre-specified covariates. Participants randomised to LGG-BB12 also had a similar risk of UTI as those not on LGG-BB12 (HR 1.29; 95% CI: 0.74–2.25; P = 0.37). Multivariable post hoc survival analysis for RC14-GR1 only vs. the other three groups showed a potential protective effect (HR 0.46; 95% CI: 0.21–0.99; P = 0.03), but this result would need to be confirmed before clinical application.ConclusionIn this RCT, there was no effect of RC14-GR1 or LGG-BB12 in preventing UTI in people with SCI.

Early use of Bladder Relaxant (Oxybutynin) in Posterior Urethral Valve Patients. Is it Justified

Introduction: Posterior Urethral Valves (PUV) constitute the most common infravesical urinary obstruction in boys. Bladder dysfunction, the pattern of which changes with the age and is common cause of morbidity in PUV patients. Urodynamic study provides a useful tool to identify the bladder dysfunction and allow timely and appropriate management. The aim of this study was to determine the efficacy of early use of bladder relaxant (oxybutynin) on urodynamic parameters in PUV patients and to compare our results with other authors. Material and Methods: Patients with posterior urethral valves more than 4 years of age were included in the study. After the diagnosis, oxybutynin was started prophylactically in all patients. Invasive urodynamic study was done in all patients minimum one year after start of oxybutynin. Bladder relaxant (oxybutynin) was stopped 48 hours before the study. Various urodynamic parameters which were noted in each patient include compliance, bladder stability (normal/overactivity), bladder capacity, detrusor pressure during voiding (sustained, waxing and waning or myogenic failure), detrusor sphincter dysynergia and post void residue. Results: 47 patients were included in the study. Age of patients ranged from 4 years to 14.8 years with mean age of 8.4 years. Normal detrusor pressure during filling (stable bladder) was seen in 95.7% of patients, bladder overactivity in 4.3% of patients, compliance (compliance good in 89.4% and compliance poor in 6.4%), bladder capacity (normal (70.2%), decreased (10.6%) and increased (19.1%), detrusor pressure during voiding (sustained (68.1%), waxing and waning (21.3%) and myogenic failure (10.6%)). Conclusion: Early use of oxybutynin immediately after the diagnosis of PUV, improves the urodynamic parameters in these patients possibly because of protective effect of oxybutynin on bladder function and structure.

Bladder dysfunction does not affect long-term success rate of the retropubic suburethral sling procedure in women with stress urinary incontinence.

This study investigated the long-term success rate of retropubic suburethral sling in the treatment of women with stress urinary incontinence (SUI) and different bladder function. Surgical outcomes of women with SUI undergoing a retropubic suburethral sling procedure between October 1989 and November 2014 were analyzed retrospectively. Bladder function was evaluated in every patient preoperatively using videourodynamic studies. Patients were classified as having stable bladder, detrusor overactivity (DO), or detrusor underactivity (DU). Baseline urodynamic parameters were analyzed and long-term therapeutic outcomes were compared among these three groups. In all, 403 patients underwent sling procedure for SUI. Of these, 291 (72.2%) had a stable bladder, 78 (19.4%) had DO, and 34 (8.4%) had DU. Mean (± SD) patient age was 60.2 ± 11.8 years, and the median follow-up was 97 months (interquartile range 24-325 months). Postoperatively, the overall continence rate was 83.4% (336/403). After surgery, 71 patients (17.6%) complained of dysuria, 14 (3.5%) complained of urgency incontinence, 25 (6.2%) had recurrent SUI requiring a secondary sling procedure, and urethrolysis was performed in 13 (3.2%). In the stable bladder, DO, and DU groups, the 5-year continence rates were 88.6%, 84.1%, and 79.4%, respectively (P = 0.59), whereas the 10-year continence rates were 83.8%, 72.9%, and 79.4%, respectively. Kaplan-Meier survival analysis indicated that the long-term success rate was similar among the three groups (P = 0.39). The overall continence rate was 83.4% and the 10-year continence rate was satisfactory in all bladder function subgroups. Treatment outcomes were the same for women with SUI but different bladder function.

Abstract 967: Development of fluorescent-cell based high throughput assay to identify novel therapeutics of bladder cancer cells through upregulation of SPARC expression

Abstract Bladder cancer is the most common malignancy affecting the urinary system with an estimated 76,960 new cases and projected 16,390 deaths in 2016 in the United States. The role of SPARC in various cancers is contextual and differs based on the tumor classification, malignancy and progression. We have recently reported the tumor suppressor effect of SPARC in urinary bladder cancer. We have shown that the loss of SPARC in bladder cancer resulted accelerated bladder carcinogenesis and metastasis multiple pathways involving cell cycle deregulation, inflammation and angiogenesis. We have also reported that SPARC protein expression significantly decreased in the cancerous compartment in advanced human bladder cancer as well as in carcinogen-induced murine urothelial cancer. However, the mechanism of the downregulation of SPARC expression in cancer in general and in bladder cancer in particular is still unraveled. The purpose of our study is to develop a robust, high throughput assay to identify therapeutic candidates as regulators of SPARC expression in bladder cancer. We cloned SPARC promoter in a third generation lentiviral vector coupled with fluorescent GFP or mCherry fluorescent protein to quantitatively measure SPARC expression. We generated stable bladder cancer cell lines expressing SPARC expression in bladder cancer cell lines. UMUC3 bladder cancer cells were transduced with lentiviral vector to generate SPARC-promoter reporter system to screen regulators of SPARC expression. Reporter cells were plated in 96 well plates and treated with 10uM of FDA-approved and natural product drug libraries. Real time monitoring of changes in SPARC expression was done by measuring GFP fluorescence intensity using IncuCyte® ZOOM Live Imaging Analysis System. We identified drugs that consistently exhibited dosage-dependent augmentation or down-regulation of SPARC expression in UMUC3 cells. Our screens identified novel up-regulators of SPARC expression that are both standard of care and novel bladder cancer therapeutics. Our efforts produced an efficient robust assay to identify novel therapeutics and regulators of the tumor suppressor SPARC in the bladder cancer ecosystem that can be used in the adjuvant and neoadjuvant settings. Citation Format: Chirayu M. Patel. Development of fluorescent-cell based high throughput assay to identify novel therapeutics of bladder cancer cells through upregulation of SPARC expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 967. doi:10.1158/1538-7445.AM2017-967

Contractile effects and receptor analysis of adenosine-receptors in human detrusor muscle from stable and neuropathic bladders.

To measure the relative transcription of adenosine receptor subtypes and the contractile effects of adenosine and selective receptor-subtype ligands on detrusor smooth muscle from patients with neuropathic overactive (NDO) and stable bladders and also from guinea-pigs. Contractile function was measured at 37°C in vitro from detrusor smooth muscle strips. Contractions were elicited by superfusate agonists or by electrical field stimulation. Adenosine-receptor (A1, A2A, A2B, A3) transcription was measured by RT-PCR. Adenosine attenuated nerve-mediated responses with equivalent efficacy in human and guinea-pig tissue (pIC50 3.65–3.86); the action was more effective at low (1–8 Hz) compared to high (20–40 Hz) stimulation frequencies in human NDO and guinea-pig tissue. With guinea-pig detrusor the action of adenosine was mirrored by the A1/A2-agonist N-ethylcarboxamidoadenosine (NECA), partly abolished in turn by the A2B-selectve antagonist alloxazine, as well as the A1-selective agonist N6- cyclopentyladenosine (CPA). With detrusor from stable human bladders the effects of NECA and CPA were much smaller than that of adenosine. Adenosine also attenuated carbachol contractures, but mirrored by NECA (in turn blocked by alloxazine) only in guinea-pig tissue. Adenosine receptor subtype transcription was measured in human detrusor and was similar in both groups, except reduced A2A levels in overactive bladder. Suppression of the carbachol contracture in human detrusor is independent of A-receptor activation, in contrast to an A2B-dependent action with guinea-pig tissue. Adenosine also reduced nerve-mediated contractions, by an A1- dependent action suppressing ATP neurotransmitter action.Electronic supplementary materialThe online version of this article (doi:10.1007/s00210-016-1255-1) contains supplementary material, which is available to authorized users.

Pelvic floor muscle functions are improved after successful transobturator vaginal mesh procedures

To explore functional changes of pelvic floor muscle (PFM) after successful Perigee procedures. We retrospectively analyzed information from 145 women having achieved anatomic success, defined as <stage II cystocele according to the pelvic organ prolapse quantification (POP-Q) system. The investigated data included results from the POP-Q system and four-dimensional ultrasound at the preoperative and 12-month postoperative evaluations. The involuntary and voluntary PFM functions were, respectively, investigated during coughing and squeezing using the ultrasound parameters of the bladder neck distance (BND), bladder neck angle (BNA), genitohiatal distance (GHD), and genitohiatal angle. Postoperatively more women displayed normal involuntary PFM function in maintaining a stable bladder neck (preoperative vs. postoperative: 4.8% vs. 22.8%, P < 0.001) and genitohiatal (preoperative vs. postoperative: 16.6% vs. 30.3%, P = 0.008) locations upon coughing and could perform voluntary PFM contractions (preoperative vs. postoperative: 49.7% vs. 64.1%, P = 0.018). Compared with preoperative manifestations, less caudal displacement of the bladder neck indicated by smaller ranges of dynamic changes in BNA following coughing (preoperative vs. postoperative: 28° vs. 12°, P < 0.001), more cranial movement of the bladder neck indicated by larger values of changes in BND following squeezing (-0.26 vs. 0.06 cm, P < 0.001), and less reduction of genitohiatal size indicated by larger values of changes in GHD following squeezing (preoperative vs. postoperative: -0.95 vs. -0.63 cm, P = 0.027) were demonstrated postoperatively. Involuntary and voluntary PFM functions are improved after successful Perigee procedures. Neurourol. Urodynam. 36:380-384, 2017. © 2015 Wiley Periodicals, Inc.

Durable Results of Mitomycin C Injection with Internal Urethrotomy for Refractory Bladder Neck Contractures: Multi-institutional Experience

IntroductionWe evaluated our intermediate term experience with radial urethrotomy and intralesional mitomycin C injection in patients with recurrent bladder neck contractures. Recurrent bladder neck contractures in which previous endoscopic treatment failed pose a difficult management dilemma. MethodsProspectively collected data were reviewed in a retrospective manner of patients presenting with recurrent bladder neck contractures from January 2007 to June 2014. All patients had at least 1 prior failed incision of a bladder neck contracture and many had additional dilations or catheter dependence. Radial cold knife incisions of the bladder neck were performed followed by injection of 0.3 to 0.4 mg/ml mitomycin C at each incision site. All surgeons performed the incision technique and injection in a reproducible fashion. ResultsA total of 40 patients underwent urethrotomy with mitomycin C injection. At a median followup of 20.5 months 30 patients (75.0%) had a stable bladder neck after 1 procedure. An additional 5 patients required 2 procedures to obtain a stable patent bladder neck (87.5%). Of the 40 patients 14 (35.0%) presented in retention on catheter drainage and all had a stable, patent bladder neck. No recurrence was detected in the original 18 patients in the pilot study with patent bladder necks. Rigorous followup revealed no long-term complications. ConclusionsUrethrotomy with mitomycin C injection for the management of recurrent bladder neck contractures is safe and efficacious. The addition of an antifibrotic agent in conjunction with internal urethrotomy offers a definitive solution to a problem that would otherwise be managed with repeat urethral incision/dilation, catheter dependence or open bladder neck reconstruction.

Can We State Stable Bladder? How Many Repetitions Should We Do for an Appropriate Demonstration of Involuntary Detrusor Contraction?

Aims: Involuntary Detrusor Contraction (IDC) may alter therapeutic plans; therefore, urodynamic demonstration (UD) is pivotal. We explore if same session repetitions enhance its demonstration and minimize false-negative results. Methods: Two hundred fifty two women (mean age 47 ± 5.7) had 4 full repetitions of UD with the last round filled with 4°C fluid (Ice-water test). IDC was diagnosed if with at least 3 cm H₂O after artifacts were ruled out. Results: 44.4% of the cases showed IDC in the first round of the exam but it could be demonstrated in 88.5% of the women if 4 rounds are taken into account. Only 2 cases showed IDC exclusively in the first round. Nine cases (3.5%) showed IDC in the first round and only on Ice-test, while all other IDC-detected cases revealed it in scattered patterns along the repetitions. Likewise, IDC detection on the second, third and fourth rounds varied widely and unpredictably, many failing to show a consistent pattern of presentation after its detection. IDC wave amplitude did not show any correlation to the detection. Conclusions: Urodynamic repetition is a necessary procedure where IDC is important to demonstrate, as its false-negative rate is high and its unpredictable pattern of detection may be improved by repetition.

Rectus fascia pubovaginal sling for recurrent stress urinary incontinence after failed synthetic mid-urethral sling: Letter.

We were very interested to read the recent study by Welk and Herschorn, and the related commentary by Steele, regarding the role of autologous rectus fascial slings for complex recurrent female stress urinary incontinence (SUI).1,2 The authors report that, on medium-term follow-up of 33 women with previous failed continence surgery, pubovaginal sling was associated with a significant reduction in pad usage and good patient satisfaction rates.1 In 2010, we reviewed the published literature on therapeutic options for managing women with recurrent SUI after failed synthetic mid-urethral sling (MUS).3 At that time, no studies reporting outcomes after PVS for a previous failed MUS had been reported and thus, the data reported by Welk and Herschorn are particularly welcome. We also recently collected data on women undergoing rectus fascial PVS for complex recurrent SUI in our tertiary urogynecology unit. Preoperative video-urodynamics was performed in all women considering PVS. The surgical technique used was very similar to that by Welk and Herschorn,1 with a 13 × 2-cm strip of rectus fascia harvested. All cases were seen in the clinic at 6 weeks and 12 months postoperatively and at variable follow-up periods thereafter. At follow-up visits, uroflowmetry and post-void residual volume were performed and subjective cure of SUI was assessed. We identified 7 women who underwent PVS after a previously failed MUS, who were contacted by telephone to complete the ICIQ-SF questionnaire4 and to ascertain cure (Table 1). Women had a median age of 61 (range: 41–73) years and were a complex group, with a median of 2 (range: 1–4) prior continence surgeries. All women completed the telephone survey and the median interval since the PVS was 5 years (range: 0.5–9 years). The long-term failure rate following PVS for recurrent SUI in our population was 14% (1/7). This patient had preoperative voiding dysfunction and was still requiring self-catheterizing 4.5 years after the PVS. A second patient required self-catheterization for de novo voiding dysfunction but was dry. Table 1. Overall, 71% (5/7) of women were completely cured and 86% (6/7) were satisfied. The rate of de novo OAB in women with a stable bladder preoperatively was 80% (4/5). One woman, with a history of known thrombophilia, suffered a large pulmonary embolus on postoperative day 12 but recovered fully. We agree with the comments of Steele that autologous PVS still has a role as a salvage procedure in complex recurrent female SUI. We found that PVS was associated with a low failure rate, but a high rate of de novo OAB at 5 years in a small population of women with previous failed synthetic MUS. Although the case of pulmonary embolus in our population raises some concern, previous work from the Urinary Incontinence Treatment Network reported a low rate (0.3%) of venous thromboembolism after PVS, which is reassuring.5

A new method of establishing orthotopic bladder transplantable tumor in mice.

ObjectiveThe present study aims to find a convenient, rapid, and stable method to establish bladder tumor in mice.MethodsFemale Balb/C-nu-nu nude mice (or female T739 mice) were narcotized by sodium pentobarbital at a dosage of 60 mg/kg. The stylet of the 24# venous retention needles was bent in a 5° to 7° angle at a distance of 15 mm from the needlepoint to form a circle with 2.61 mm to 3.66 mm radius when the stylet is rotated. The pipe casing was lubricated with liquid paraffin, and inserted into the bladder cavity. The drift angle stylet was inserted into the pipe casing slowly, rotated for five times, and then pulled out. A cell suspension (0.1 mL) of approximately 1×106 T24 cells (or BTT cells) was then injected immediately.ResultsA total of 60 T739 mice and 60 Balb/C-nu-nu nude mice were inoculated with BTT cells and T24 cells, respectively. The bladder tumor incidence and the average survival time of the tumor-bearing mice were 100% and (26.69±9.24) d and 100% and (34.59±9.8) d for the T739 mice and Balb/C-nu-nu nude mice, respectively.ConclusionsUsing the drift angle stylet to injure the mucous membrane of the urinary bladder can establish a stable bladder transplantable tumor model in mice.

Construction of Fibulin-5 eukarvotic expression vector and establishment of its stable transfected bladder cancer cell line

Objective To construct eukaryotic expression vector of Fibulin-5 and establish stable human bladder cancer cell line.Methods Fibulin-5 cDNA in hDANCE_CFLAG plasmid was amplified by polymerase chain reaction (PCR).The amplified products were cloned into pMD-19T simple vector.The pMD-19T-Fibulin-5 vector was cut by Xho Ⅰ and EcoR Ⅰ to generate a Xho Ⅰ-Fibulin5-EcoR Ⅰ fragment that was ligated into enhanced green fluorescent protein carrier ( p-EGFP-N1 ) plasmid to synthesize p-EGFP-Fibulin-5 plasmid,which was then cut by Bg Ⅲ.Finally,the p-EGFP-Fibulin-5 plasmid was transfected into bladder cancer cell line 5637 by liposomes.Results The length of PCR products was 1429 bp.The results of DNA sequencing for the fragments by Xho Ⅰ and EcoR Ⅰ suggested the correct insertion of Fibulin5 cDNA.A band with about 450 bp was generated after p-EGFP-Fibulin-5 plasmids were digested by BgⅢ.The successfully transfected cells by pEGFP-Fibulin-5 or pEGFP-N1 emitted green fluorescence.Conclusion Fibulin-5 eukaryotie expression vector was successfully constructed and transfected to human bladder cancer cell line. Key words: Bladder carcinoma; Eukaryotic expression vector; Transfection; Fibulin-5