Improving the barrier function of damaged cultured urothelium using chondroitin sulfate.

AIMS: To determine whether glycosaminoglycan (GAG) replenishment is able to improve recovery of a deficient urothelial barrier, chondroitin sulfate (CS) instillations were tested using an in vitro model. Porcine urothelial cells (Ucells) were terminally differentiated in culture conditions to construct a urothelial layer with a functional barrier. This layer was damaged to compromise barrier function to simulate a key characteristic of bladder pain syndrome/interstitial cystitis. The functional effect of subsequent treatment with CS was evaluated. METHODS: Primary porcine Ucells were isolated and cultured on inserts. Differentiation of cells was evaluated with immunohistochemical analysis for the presence of umbrella cells, tight junctions and CS. Transepithelial electrical resistance (TEER) measurements were performed to evaluate barrier function. Protamine was used to simulate mild urothelial damage. CS 0.2% (vol/vol), a GAG, was subsequently instilled in the treatment group. The recovery of barrier function was further evaluated with TEER measurements. The Student t test was used for the analysis of results. RESULTS: After induction of differentiation, the Ucells expressed barrier markers and a functional barrier was established (measured by high TEER). TEER decreased significantly after instillation with protamine. CS instillation improved recovery of TEER significantly measured after 7 hours (84% vs 22% in controls). After 24 hours; however, the TEER was comparable in both experimental groups. CONCLUSION: CS instillation improves the recovery of the urothelial barrier after damage in vitro. This functional experiment shows that CS improves recovery of damaged urothelial function, which supports the hypothesis behind the mechanism of action of GAG-replenishment therapy.

Survival of the artificial urinary sphincter in a changing patient profile.

PURPOSE: To examine the functional survival of the artificial urinary sphincter (AUS) AMS800 in a changing patient population. Because of increasing experience and dexterity of the operating team, we hypothesize that patients with known risk factors nowadays have a better survival of their prosthesis. However, due to a change to a more complex case mix, overall results appear to be worse. MATERIALS AND METHODS: All men who underwent implantation of an AUS between 2001 and 2016 because of urethral sphincter deficiency were retrospectively analyzed. Patients were divided in groups based on date of surgery and number of patients: 2001-2009 (G1), 2010-2013 (G2), 2014-2016 (G3). Baseline characteristics and additional therapies prior to implantation were analyzed in all groups. Risk factors for failure only in G1 and G2. Revision or explantation of the AUS was used as endpoint. Kaplan-Meier analysis was used to calculate survival of the device. RESULTS: A total of 129 patients (mean age 72 ± 9 years) underwent 129 primary implants, and 11 secondary implants. Median follow-up was 5.74 years in G1, 3.26 years G2 and 1.54 years G3. Approximately 25% of the patients in G1 had received adjuvant therapy for prostate cancer and 14% underwent previous surgery for incontinence. In G2, 51 and 55% underwent adjuvant therapy for prostate cancer and previous surgery for incontinence, respectively, G3 was comparable. The overall 50% survival improved in patients with radiotherapy and previous incontinence surgery in G2 as compared to G1. CONCLUSIONS: Despite the more complex patient population, the survival of the AUS did not decrease. In some patient categories, the AUS functional survival is even still improving over the past few years.

[Severe vaginal discharge following rectal surgery]. / Ernstige fluor vaginalis na rectumresectie.

BACKGROUND: Almost 50% of women who have had rectal surgery subsequently develop vaginal discharge. Due to the recurrent and unexpected nature of this heavy discharge, they often experience it as very distressing. Many of these women undergo extensive diagnostic tests that are mainly focused on identifying fistula formation. If no fistula is found, in most cases no other cause for severe vaginal discharge can be demonstrated. CASE DESCRIPTION: In our practice, we saw three patients (49-, 54- and 74-years-old, respectively) with similar severe vaginal discharge after rectal surgery and in whom no explanation for the vaginal discharge could be found. For this reason we conducted a literature search into this condition. CONCLUSION: Anatomical changes appear to be responsible for heavy vaginal discharge following rectal surgery. Changes in pelvic floor muscles and compression of the distal part of the vagina may lead to pooling of fluid in the proximal part of the vagina, resulting in severe discharge. Symptomatic treatment may reduce the symptoms.

Urothelium update: how the bladder mucosa measures bladder filling.

AIM: This review critically evaluates the evidence on mechanoreceptors and pathways in the bladder urothelium that are involved in normal bladder filling signalling. METHODS: Evidence from in vitro and in vivo studies on (i) signalling pathways like the adenosine triphosphate pathway, cholinergic pathway and nitric oxide and adrenergic pathway, and (ii) different urothelial receptors that are involved in bladder filling signalling like purinergic receptors, sodium channels and TRP channels will be evaluated. Other potential pathways and receptors will also be discussed. RESULTS: Bladder filling results in continuous changes in bladder wall stretch and exposure to urine. Both barrier and afferent signalling functions in the urothelium are constantly adapting to cope with these dynamics. Current evidence shows that the bladder mucosa hosts essential pathways and receptors that mediate bladder filling signalling. Intracellular calcium ion increase is a dominant factor in this signalling process. However, there is still no complete understanding how interacting receptors and pathways create a bladder filling signal. Currently, there are still novel receptors investigated that could also be participating in bladder filling signalling. CONCLUSIONS: Normal bladder filling sensation is dependent on multiple interacting mechanoreceptors and signalling pathways. Research efforts need to focus on how these pathways and receptors interact to fully understand normal bladder filling signalling.

TRPV4 channels in the human urogenital tract play a role in cell junction formation and epithelial barrier.

AIM: The molecular interactions between transient receptor potential vanilloid subtype 4 channels (TRPV4) and cell junction formation were investigated in the human and mouse urogenital tract. MATERIALS AND METHODS: A qualitative study was performed to investigate TRPV4 channels, adherence junctions (AJs) and tight junctions (TJs) in kidney, ureter and bladder tissues from humans and wild-type and transgenic TRPV4 knockout (-/-) mice with immunohistochemistry, Western blotting, immunoprecipitation and reverse trasnscription-PCR. Cell junction formation in the wild-type and TRPV4 knockout (-/-) mouse was evaluated with immunohistochemistry and transmission electron microscope (TEM) techniques. RESULTS: TRPV4 channels are predominantly located in membranes of epithelial cells of the bladder, ureter and the collecting ducts of the kidney. There is a molecular interaction between the TRPV4 channel and the AJ. TEM evaluation showed that AJ formation is disrupted in the TRPV4 -/- mouse resulting in deficient intercellular connections and integrity of the epithelium. CONCLUSIONS: TRPV4 is believed to be a mechanoreceptor in the bladder. This study demonstrates that TRPV4 is also involved in intercellular connectivity and structural integrity of the epithelium.

Can preoperative urodynamic investigation be omitted in women with stress urinary incontinence? A non-inferiority randomized controlled trial.

AIMS: To assess in women with stress urinary incontinence (SUI) the value of urodynamics prior to treatment. METHODS: We performed a multicenter non-inferiority randomized controlled trial. Women with SUI were randomly allocated to management based on a workup with or without urodynamics. The primary outcome was clinical reduction of complaints as measured with the Urogenital Distress Inventory urinary incontinence subscale (UDI-UI) at 12 months after the onset of treatment. A mean difference in improvement of less than 8 was considered non-inferior. The study was analyzed according to intention-to-treat. RESULTS: The trial was stopped prematurely because of slow recruitment. We randomly allocated 59 women to a strategy with (N = 31) or without (N = 28) urodynamics. The mean difference in improvement on the UDI-UI was 14 in favor of the group without urodynamics (48 SD ± 22 vs. 34 SD ± 22, 95% CI: -28 to -0.26), confirming non-inferiority. Addition of urodynamics did not result in a lower occurrence of de novo overactive bladder complaints compared to a workup without urodynamics (6/31 vs. 1/28; RR 5.4, 95% CI: 0.70-42). In the group allocated to urodynamics, initial surgical management was more often abandoned compared to the group not allocated to urodynamics (5/31 vs. 1/28; RR 4.5, 95% CI: 0.56-36). CONCLUSIONS: In this relatively small study, the omission of urodynamics was not inferior to the use of urodynamics in the preoperative workup of women with SUI. Women with SUI undergoing urodynamics had the risk of a choice for more prudent treatment, which seemed to result in a delay until effective treatment.

Clinical results of a brindley procedure: sacral anterior root stimulation in combination with a rhizotomy of the dorsal roots.

The Brindley procedure consists of a stimulator for sacral anterior-root stimulation and a rhizotomy of the dorsal sacral roots to abolish neurogenic detrusor overactivity. Stimulation of the sacral anterior roots enables micturition, defecation, and erections. This overview discusses the technique, selection of patients and clinical results of the Brindley procedure. The Brindley procedure is suitable for a selected group of patients with complete spinal cord injury and detrusor overactivity. Overall, the Brindley procedure shows good clinical results and improves quality of life. However, to remain a valuable treatment option for the future, the technique needs some adequate changes to enable analysis of the implanted parts, to improve revision techniques of the implanted parts, and to abolish the sacral dorsal rhizotomy.

Minimal invasive electrode implantation for conditional stimulation of the dorsal genital nerve in neurogenic detrusor overactivity.

STUDY DESIGN: Experimental. OBJECTIVES: Electrical stimulation of the dorsal genital nerves (DGN) suppresses involuntary detrusor contractions (IDCs) in patients with neurogenic detrusor overactivity (DO). The feasibility of minimal invasive electrode implantation near the DGN and the effectiveness of conditional stimulation to suppress IDCs at different amplitudes in spinal cord injury (SCI) patients with DO were studied. SETTING: Radboud University Nijmegen MC, The Netherlands. METHODS: In eight healthy volunteers, a needle electrode was inserted from both a medial and lateral-to-midline site at the level of the pubic bone. Electrode insertion was guided by the genito-anal reflex (GAR) evoked by electrical stimulation and by sensation to this stimulation. In eight SCI patients with DO, the bladder was repeatedly filled and emptied partially in between. Conditional stimulation using a needle electrode was applied when an IDC was observed at urodynamics. Different amplitudes were used during each filling. Control cystometry was carried out before electrode insertion and after stimulation. RESULTS: The lateral implant approach was preferred, as it was easier to manoeuvre the needle along the pubic bone and fixate the needle. In SCI patients, the electrode was positioned successfully, and IDCs were suppressed (range 1-6 IDC suppressions) with conditional stimulation at maximum tolerable amplitude, except for one patient. Stimulation was less effective at lower amplitudes. Stimulation lowered the intensity of bladder sensations concomitant with IDC. CONCLUSION: The lateral-to-midline implant approach, in combination with GAR and sensation to stimulation, is feasible for electrode implantation near the DGN in SCI patients. Conditional stimulation effectively suppresses IDCs.

No primary role of ambulatory urodynamics for the management of spinal cord injury patients compared to conventional urodynamics.

AIMS: Adequate urodynamic assessment of bladder behavior is essential in spinal cord injury (SCI) patients. Ambulatory urodynamics are more sensitive to detect detrusor overactivity (DO) than conventional urodynamics. The primary objective of this study was to determine the value of ambulatory urodynamics for the diagnosis of DO in SCI patients compared to conventional urodynamics. METHODS: Twenty-seven SCI patients who were suspected of DO underwent both conventional and ambulatory urodynamics at one day. A single involuntary detrusor contraction (IDC) was defined as a detrusor pressure rise of at least 10 cmH(2)O. DO according to the ICS definition was used in addition to minimize the influence of catheter artifacts. Outcome of urodynamics was used for decisions on treatment. RESULTS: Ambulatory urodynamics were more sensitive to diagnose IDC and DO. Conventional urodynamics had a sensitivity of 82% and specificity of 75% for DO diagnosis compared to ambulatory urodynamics. Mean maximum detrusor pressures did not differ significantly between both urodynamics. When the maximum detrusor pressure at conventional urodynamics did not exceed 40 cmH(2)O, 83% (10/12) of patients had a mean maximum detrusor pressure under 40 cmH(2)O at ambulatory urodynamics. Although the inter-individual DO diagnostic agreement was lower for ambulatory than conventional urodynamics (58%, K = 0.201 vs. 77%, K = 0552), the treatment agreement was higher for ambulatory urodynamics (58% vs. 42%). CONCLUSIONS: Ambulatory urodynamics do not seem necessary for diagnosis and risk assessment in SCI patients suspected for DO when conventional urodynamics are done properly. The exact role of urodynamics in treatment decision remains to be determined.

Limited value of bladder sensation as a trigger for conditional neurostimulation in spinal cord injury patients.

AIMS: Conditional stimulation of dorsal genital nerves suppresses undesired detrusor contractions (UDC) and consequently increases bladder capacity and prevents incontinence. No clinically applicable sensor exists for reliable bladder activity monitoring as a trigger for conditional stimulation. Primary objective of this study was to determine whether bladder sensation concomitant with UDC may be used for spinal cord injury (SCI) patients to trigger neurostimulation in daily life. METHODS: Nineteen male and 7 female SCI patients suspected of detrusor overactivity (DO) underwent conventional and 6-hr ambulatory urodynamics. Patients were instructed to do normal daily activities and to activate event buttons of the ambulatory recorder to mark events: physical activity, bladder sensation, micturition or intermittent catheterization, and urinary incontinence. Detection rate was defined as the number of recorded bladder sensation divided by the total number of recorded UDC during ambulatory urodynamics. RESULTS: Bladder sensation was reported by 73% of patients in daily life. Only 41% of patients had analyzable bladder sensation concomitant with UDC during ambulatory urodynamics. For ambulatory and conventional urodynamics, mean detection rates were 23% and 72%, respectively, with mean recording delays of 57 and 16 sec after UDC onset, respectively. CONCLUSIONS: Bladder sensation only occurs in a small group of SCI patients combined with a rather low detection rate and long reaction time. Therefore, bladder sensation as a trigger for conditional stimulation does not seem to be suitable for SCI patients with DO. Reliable techniques for chronic bladder activity monitoring are a prerequisite for successful clinical application of conditional stimulation.

Urethral instability: current pathophysiological concept.

The role of urethral pressure variations during filling cystometry is seldom assessed as a potential cause of voiding dysfunction and/or storage disorders. In this article, we review current research in the field of urethral pressure variations and discuss the way of determining urethral pressure variations, its value for the clinical practice and hypothesize the origin of urethral pressure variations. The observation and recognition of urethral pressure variations (urethral instability) could be valuable in the diagnosis and evaluation of therapy in functional lower urinary tract disorders.

ProACT for stress urinary incontinence after radical prostatectomy.

INTRODUCTION: Stress urinary incontinence is a bothersome complication of radical prostatectomy. Surgical treatment consists of the artificial urinary sphincter (AUS), the male sling and bulk injections. This study presents the results of the first series of implantations of ProACT in the Netherlands. MATERIALS AND METHODS: A non-validated questionnaire was sent to 29 male patients implanted with ProACT to determine Stamey score, pad count and questions about quality of life and satisfaction. Complications, revisions and explantations were registered. RESULTS: Mean follow-up was 41 months. Based on Stamey score four patients are continent at the end and nine patients according to the pad count. The average pad count decreased significantly. Remarkable was the high rate of dislocations and revisions and patients' satisfaction. CONCLUSIONS: ProACT is a less invasive treatment compared to the AUS. However, the procedure is associated with a substantial revision and explantation rate. ProACT can be part of a so-called step-up approach before opting for a more invasive treatment.

Applications of neurostimulation for urinary storage and voiding dysfunction in neurological patients.

The application of various forms of electrical stimulation is considered a therapeutic option to manage different types of lower urinary tract dysfunction. However, even though lower urinary tract dysfunction is common in patients with neurological disease, apart from patients with spinal cord injury, electrostimulation is still not widely applied in a neurological patient population. Urologists frequently encounter patients with neurogenic lower urinary tract dysfunction in their daily practice. Often, the conservative treatment modalities do not offer adequate relief of symptoms in these patients. In most cases, surgical options including transurethral stents, augmentation cystoplasty stoma or derivation surgery are considered a last resort. With this in mind, it is essential that healthcare professionals are informed about the possibilities of nerve stimulation in neurogenic patients. We review the utilization and the results of electrical stimulation by means of pudendal nerve stimulation, stimulation of the sacral nerve roots and lower limb stimulation in patients with neurogenic detrusor overactivity.

Extracorporeal magnetic innervation therapy: assessment of clinical efficacy in relation to urodynamic parameters.

OBJECTIVE: Clinical efficacy and urodynamic changes in women treated by extracorporeal magnetic innervation therapy (ExMI) were studied. MATERIAL AND METHODS: Women, presenting with urge, stress and mixed urinary incontinence, were included in a prospective study. ExMI was applied by an electromagnetic chair. To document clinical efficacy, a voiding diary and visual analogue scale were completed before and after treatment, together with a pad test. Detrusor overactivity (DO) and urethral instability (URI) were urodynamically documented. Clinical success was defined as more than 50% improvement in symptoms. RESULTS: Sixteen patients were included. At baseline, DO was observed in 10 patients, and URI in 12 patients. DO did disappear at follow-up in 60%, and a decrease in URI was seen in 66%. No significant clinical improvement was seen at follow-up. CONCLUSION: Although significant changes in urodynamic variables were observed, no significant improvement in clinical efficacy was seen after ExMI.

[Male urinary incontinence]. / Incontinentie bij de man.

*Urinary incontinence in males is gaining increasingly more attention. *Male urinary incontinence can be classified as storage incontinence due to overactive bladder syndrome or stress incontinence due to urethral sphincter dysfunction. *Most patients benefit from the currently available treatment options for overactive bladder, which include physiotherapy, medication, botulinum A toxin injections and neuromodulation techniques. *The number of radical prostatectomies performed for prostate cancer is increasing; this intervention can lead to stress incontinence due to sphincter weakness. *Various treatment options are available for stress incontinence due to sphincter weakness. *In addition to physiotherapy, treatment options also include the artificial urinary sphincter, which has been available for decades. *New treatments include para-urethral balloons and male slings. The value of these approaches must be proven in the coming years.

[The practice guideline 'Urinary incontinence' (first revision) from the Dutch College of General Practitioners; a response from the perspective of urology]. / De standaard 'Incontinentie voor urine' (eerste herziening) van het Nederlands Huisartsen Genootschap; reactie vanuit de urologie.

The revised practice guideline 'Urinary incontinence' of the Dutch College of General Practitioners contains some important changes. Urodynamic investigation is not mandatory for differentiating between types of incontinence in the general practice setting. Physical examination including a valsalva leak point test is considered important. From a urological point ofview it remains to be seen whether the history-taking and the physical examination described in the revised guideline will be enough to accurately differentiate between the possible incontinence types. The practice guideline underlines a role for the general practitioner in teaching bladder training or pelvic floor exercises. The benefits of this compared to exercises taught by specialized physiotherapists will have to be determined. Another new feature is that antimuscarinic drugs are mentioned as proper treatment for people suffering from overactive bladder complaints. The practice guideline advises referral of male incontinence patients only if the incontinence is not related to prostate surgery. However, patients with postoperative incontinence should also be referred as there are good diagnostic and therapeutic options available.

[Some complications of tension-free midurethral tapes for the treatment of stress incontinence in women]. / Enkele complicaties van spanningsvrije midurethrale tapes voor de behandeling van stressincontinentie bij vrouwen.

Complications occurred in two women of 45 and 54 years of age who were treated with tension-free midurethral sling procedures. The first woman was treated with transobturator tape due to stress incontinence and an overactive bladder. The procedure resulted in a worsening of the overactive bladder. The second woman was treated with tension-free vaginal tape (TVT) due to stress incontinence and subsequently suffered from pain on urinating. In the first patient, the tape was found to be too tight and following adjustment of the tape tension, the overactive bladder symptoms and the stress incontinence disappeared. The second woman experienced bladder erosion on the right side. After removal of the tape, the symptoms disappeared but the stress incontinence returned. During the last few years, the surgical treatment of stress urinary incontinence has shifted towards the positioning of tension-free tapes. Because this minimally invasive technique is fairly simple to perform, the number of anti-incontinence surgical procedures has increased threefold in the last 4 years in the Netherlands. The literature states high success rates and low complication percentages. However, in everyday practice, these results cannot always be achieved. Doctors should therefore show caution when selecting patients for tension-free midurethral tape procedures. Furthermore, patient information should clearly indicate the actual results. Initial treatment for stress incontinence should consist of intensive pelvic floor muscle training.

Urethral instability and sacral nerve stimulation-a better parameter to predict efficacy?

PURPOSE: Urodynamic parameters that predict the outcome of sacral nerve stimulation are difficult to define. We studied the predictive value of urethral instability and other urodynamic parameters on the efficacy of sacral nerve stimulation. MATERIALS AND METHODS: Patients with refractory voiding disorders were implanted with a neurostimulator after responding with more than 50% improvement in main symptoms after percutaneous nerve evaluation. Filling cystometry was performed with 3 urethral sensors and 1 bladder sensor at baseline and 6 months after implantation. Urethral pressure variations more than 15 cm H(2)O were considered pathological and defined as urethral instability. Clinical efficacy was evaluated by voiding diary data and defined as successful when greater than 50% improvement was observed. RESULTS: A total of 19 female patients enrolled in the study. At baseline detrusor overactivity was observed in 9 patients, while 18 showed urethral instability. Sacral nerve stimulation therapy was successful in 13 patients (68%). The number of pads used per day and the severity of leakage decreased significantly. Of the 13 successfully treated patients 12 showed urethral instability at baseline. Detrusor overactivity was present in 4 successfully treated patients. Urethral instability disappeared in 7 of the 13 successfully treated patients and detrusor overactivity disappeared in only 1 of these patients. CONCLUSIONS: In this study urethral instability appeared to be a valuable urodynamic parameter for predicting the outcome of sacral nerve stimulation.