Storage Dysfunction Research Articles

1503 PELVIC RADIOTHERAPY MORE PROFOUNDLY AFFECTS BLADDER STORAGE FUNCTION IN THE BLADDER SUFFERING FROM IRREVERSIBLE INFRA-SACRAL NEUROPATHIC BLADDER

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction1 Apr 20111503 PELVIC RADIOTHERAPY MORE PROFOUNDLY AFFECTS BLADDER STORAGE FUNCTION IN THE BLADDER SUFFERING FROM IRREVERSIBLE INFRA-SACRAL NEUROPATHIC BLADDER Noritoshi Sekido, Shiro Hinotsu, and Toru Shimazui Noritoshi SekidoNoritoshi Sekido Ibaraki, Japan More articles by this author , Shiro HinotsuShiro Hinotsu Kyoto, Japan More articles by this author , and Toru ShimazuiToru Shimazui Ibaraki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1482AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The serious bladder dysfunction after pelvic radiotherapy (PRT) was regarded as a rare adverse event. On the other hand, it was reported that bladder storage dysfunction could be more severe when PRT was added after radical pelvic surgery, such as abdominal radical hysterectomy, than when PRT or surgery was performed as a sole therapy. It is not well understood whether reversibility of the infra-sacral neuropathic bladder (NB) caused by radical pelvic surgery influences a bladder storage function after PRT. We investigate an impact of the PRTon bladder storage function with regard to the presence or absence of surgery and the reversibility of infra-sacral NB. METHODS We retrospectively reviewed urodynamic findings in 15 otherwise normal patients with stress urinary incontinence (SUI), 15 neurologically normal patients with successfully preserved native bladder after chemoradiotherapy for invasive bladder cancer (CRT), 30 patients after abdominal radical hysterectomy (ARH), and 31 patients after ARH with adjuvant pelvic radiotherapy (ARH/RT). In addition, patients with ARH or ARH/RT were divided according to the reversibility of infra-sacral NB. We performed analysis of variance of bladder compliance (Vcomp, mL/cmH2O) of each group, and the post hoc analysis using Dunnett′s test with SUI as the control group. We calculated odds ratio by logistic regression for low compliance bladder (LC: Vcomp<20 mL/cmH2O) using ARH and PRT as explanatory variables. In addition, we examined the effect of the PRT in ARH and ARH/RT with regard to reversibility of NB by Fisher exact test. P<0.05 was considered as statistically significant. RESULTS The mean Vcomp was 97.4, 52.4, 37.8, and 19.0 in SUI, CRT, ARH, and ARH/RT, respectively (p<0.0001). Vcomp in CRT (p=0.0051), ARH (p<0.0001), and ARH/RT (p<0.0001) was smaller than Vcomp in SUI. Odds ratio was 4.7 for ARH, and 11.3 for PRT. Therefore, odds ratio was numerically about 53 for ARH plus PRT, which demonstrated considerable increased risk of occurrence of LC when PRT was performed after radical pelvic surgery. In addition, seventy nine percent of irreversible NB patients after ARH/RT showed LC, whereas only forty two percent of reversible NB patients after ARH/RT showed LC (p=0.042). CONCLUSIONS Storage dysfunction is exaggerated by adjuvant radiotherapy, especially in the patients with irreversible NB. It was suggested that tolerable radiation dose is different between the bladder in reversible NB and the bladder in irreversible NB. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e602-e603 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Noritoshi Sekido Ibaraki, Japan More articles by this author Shiro Hinotsu Kyoto, Japan More articles by this author Toru Shimazui Ibaraki, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Alpha1‐Adrenoceptor Antagonists Improve Bladder Storage Function Through Reduction of Afferent Activity in Rats With Bladder Outlet Obstruction

Using a rat BOO model, we determined whether α1-adrenoceptor (AR) antagonists (silodosin, prazosin) improve the bladder storage function by reducing afferent input from the lower urinary tract. Male rats received partial bladder outlet obstruction or sham surgery were used. Four weeks following surgery, their voiding behavior was measured in a metabolic cage. BOO-rats were administered silodosin, prazosin or vehicle for 2 weeks subcutaneously using osmotic pump. At the post-drug condition, voiding behavior was measured again. The L6 spinal cord was removed and immunostained using anti c-Fos antibody. The rats were also performed continuous cystometry with saline without anesthesia or restraint at the pre- and post-drug conditions. Metabolic cage study showed the voiding behavior of BOO-rats was characterized by increase in frequency of urination and decrease in volume voided. Cystometric evaluation also showed the significant increase both in the number of successive voiding contraction and in contraction pressure. The administration of silodosin or prazosin significantly decreased urinary frequency and the number of micturition reflex but affected neither bladder contraction pressure nor residual volume. The number of c-Fos-positive cell significantly increased in BOO-rats, while significantly decreased in those receiving αl-AR antagonists. The present study demonstrates that α1-AR antagonists silodosin and prazosin have an inhibitory effect on afferent input from the lower urinary tract independently of reducing urethral resistance, and thereby reduce the storage dysfunction secondary to BOO. This result suggests that αl-AR, particularly αlA-AR, may play an important role in the activation of the afferent pathway.

Long-term lower urinary tract dysfunction after radical hysterectomy in patients with early postoperative voiding dysfunction: reply to comments by Sansone et al.

Dear Editor, We would like to thank Sansone et al. [1] for their interest in our article [2]. In response, we have the following comments. Late lower urinary tract (LUT) dysfunction such as decreased bladder compliance, detrusor overactivity, urinary incontinence, and voiding dysfunction usually resolve within 6–12 months. We hypothesized that some of them may persist beyond 1 year. LUT dysfunction is the most common long-term complication which may affect quality of life. Our focus was on the long-term sequelae. Since cancer recurrence beyond 2 year is infrequent, we chose to explore the LUT dysfunction at least 2 years after radical hysterectomy. Median time since surgery in our study was 5 years (2–11 years), which was similar in both groups (groups A and B). Age has been determined to be the most significant risk factor for LUT dysfunction [3]. Although median age in the patients after surgery (groups A and B) is higher than the patients before surgery (group C), there was no statistical significance. Voiding dysfunctions in the difference were diagnosed from both validated questionnaire (UDI and IIQ) and urodynamic studies and were more prevalent in the patients after surgery. Patients who had early postoperative voiding dysfunction (group A) were particularly affected. In contrast, storage dysfunction as diagnosed by urodynamic studies was similar in all groups. We agree that the followup timing may be one of the major factors that influence the detection of bladder dysfunction after radical hysterectomy. However, it is interesting to note that only voiding dysfunction was significantly higher in the patients after surgery, despite that storage dysfunction should be more common. If the follow-up timing had an effect to the incidence of LUT dysfunction, patients after surgery should have a significantly higher incidence of both storage and voiding dysfunction. From our result, it was possible that only voiding dysfunction may persist in the long term. Early voiding dysfunction might influence late voiding dysfunction. However, we agree that large prospective trials should be conducted to prove this possibility. Neurological damage from radical surgery, especially the loss of control from alpha adrenergic receptors, will relax the internal urethral sphincter at the bladder neck and proximal urethra, causing stress urinary incontinence. Benedetti-Panici et al. reported that maximal urethral closure pressure (MUCP) decreased significantly after type 3–4 radical hysterectomy [4]. Although, MUCP was lower in patients after surgery and lowest in group A, there was no significant difference noted. This parameter was shown in Table 2 (page 98). No patient had MUCP lower than 20 cmH2O even in patients who were diagnosed as experiencing urodynamic stress incontinence. Our finding was similar to the report of Lin et al. [5]. We agree that large prospective trials with a translational component including multicenter collaboration would be beneficial to draw definite conclusions. T. Manchana :C. Prasartsakulchai Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand

Clinical Correlates of Voiding Symptoms in Women Without Overt Urethral Obstruction

Background We hypothesized that voiding symptoms in women with normal free uroflow were not related to irritative symptoms and bladder storage dysfunction. Purpose This study was designed to explore the clinical associations between voiding symptoms in women without obvious anatomic urethral obstruction and dysfunctional voiding. Methods We retrospectively reviewed an urodynamic database and identified 335 women who had a positive response to the category of voiding symptoms in a questionnaire. All 335 women had undergone urodynamic studies and urethrocystoscopic examinations for voiding symptoms. None of the women had inappropriate sphincteric activity during voiding or anatomic evidence of urethral obstruction. In addition to categorization by menopausal status, the study subjects were further stratified based on the maximum flow rate on free uroflowmetry into two groups: the low flow group and the normal flow group. A further 125 women with lower urinary tract symptoms but without voiding symptoms and who had negative urodynamic findings were identified and served as controls. Results Of the 335 women, 137 (41%) belonged to the low flow group, including 73 pre-menopausal women and 64 postmenopausal women; 198 (59%) belonged to the normal flow group, including 127 premenopausal women and 71 postmenopausal women. Among premenopausal women, the frequency of irritative symptoms was significantly higher for those with voiding symptoms than for those without voiding symptoms. Urodynamic studies showed that lower flow rates, prolonged time to maximum flow, higher micturition resistance, and high postvoid residual urine volume were common characteristics of women with low uroflow. Irritative symptoms and bladder storage dysfunction (lower first desire to void volume and maximum cystometric capacity) were the common characteristics of premenopausal women with voiding symptoms. Conclusion Our study revealed the interesting finding that voiding symptoms in premen-opausal women with normal uroflow are associated with irritative symptoms and that bladder storage dysfunction may cause voiding symptoms.

The close relationship between life-threatening breathing disorders and urine storage dysfunction in multiple system atrophy

Survival of multiple system atrophy (MSA) depends on whether a variety of sleep-related breathing problems as well as autonomic failure (AF) occur. Since the brainstem lesions that cause respiratory and autonomic dysfunction overlap with each other, these critical manifestations might get worse in parallel. If so, the detection of AF, which is comparatively easy, might be predictive of a latent life-threatening breathing disorder. In 15 patients with MSA, we performed autonomic function tests composed of postural challenges and administered a questionnaire on bladder condition, as well as polysomnography and laryngoscopy during wakefulness and under anesthesia. Polysomnographic variables such as the apnea-hypopnea index (AHI) and oxygen saturation (SpO(2)) and the findings of laryngoscopy were compared with the degree of cardiac and urinary autonomic dysfunction. AHI, mean SpO(2) and the lowest SpO(2) showed significant correlations with urine storage dysfunction. In addition, patients with vocal cord abductor paralysis (VCAP) or central sleep apnea (CSA) contributing to nocturnal sudden death had more severe storage disorders than those without. On the other hand, no significant relationship between polysomnographic variables and orthostatic hypotension was observed except in the case of mean SpO(2). These results indicate that life-threatening breathing disorders have a close relationship with AF, and especially urine storage dysfunction. Therefore, longitudinal assessment of deterioration of the storage function might be useful for predicting the latent progress of VCAP and CSA.

TRPV4 as a target for bladder overactivity

Several papers published in the last 2-3 years suggest that transient receptor potential vanilloid 4 (TRPV4) channels are candidates as mechanosensors in the urinary bladder (including human) and indicate that modulation (inhibition) of these channels could represent a novel therapy for overactive bladder and storage dysfunction. The effects of only agonists on the bladder have been described up to now, although some compounds endowed with antagonistic activity were reported in the last year. Therefore, it is to be hoped that the effects of these compounds in different models of bladder overactivity will be evaluated.

Pharmacological and genetic analysis of mechanisms underlying detrusor overactivity in rats

Suprapontine lesions, such as those resulting from cerebrovascular disease, cause bladder storage dysfunction. Detrusor overactivity (DO) following cerebral infarction may be explained by impairment of the suprapontine regulatory system. However, precise mechanisms underlying DO is not clear. The following studies were undertaken to examine pharmacological and genetic mechanisms of DO in rats. Mechanisms of long-lasting DO in rats with cerebral infarction require signal transfer, which begins with the opening of glutamate receptors at the dorsal pontine tegmentum. DO induced by cerebral infarction has been proven to be accompanied by an increase in c-fos and zif268 expression in the dorsal pontine tegmentum and periaqueductal gray and mediated by the activation of N-methyl-D-aspartate (NMDA) receptors, cyclooxygenase-2 (COX-2), and prostaglandin E synthase (PGES). Therefore, the arachidonic acid cascade is dynamically activated in the brain after brain ischemia. Bladder sensory pathways are potential targets for drugs used to treat various bladder dysfunctions because of their role in storage symptoms (i.e., urgency, frequency) and in triggering reflex bladder activity. Antimuscarinic drugs and alpha(1)-blockers are the main treatments for overactive bladder, a condition caused by neurologic lesions, aging, bladder outlet obstruction, and other pathologies. These drugs affect sensory bladder storage symptoms, suggesting an action on bladder and urethral afferent pathways. Using animal models of DO, we demonstrated that these drugs improved bladder storage function via suppression of C-fiber afferent nerves from the lower urinary tract.

Lower urinary tract dysfunction in MS: management in the community

Lower urinary tract dysfunction in multiple sclerosis is common and is highly amenable to treatment. Individuals may have bladder storage and/or voiding dysfunction. The risk of progression to renal failure is low and hence lower urinary tract dysfunction should be considered medically manageable in most individuals. Evaluation begins with history taking and is supplemented by using a bladder diary. Ultrasonography is used to assess the degree of incomplete bladder emptying, and for assessing upper urinary tract damage. Incomplete bladder emptying is most often managed by clean intermittent self-catheterization and should be initiated if post-void residual urine is greater than 100 mls. Storage symptoms are most often managed using antimuscarinic medications. Other options include desmopressin or detrusor muscle injection of botulinum toxin type A. There are specific situations where specialist urology services should be involved.

Two Successful Vaginal Births after Cesarean Section in a Patient with Hermansky-Pudlak Syndrome Who Was Treated with 1-Deamino-8-Arginine-Vasopression during Labor

We describe the obstetric management for a patient with Hermansky-Pudlak syndrome (HPS) and a previous cesarean delivery. The disease is characterized by oculocutaneous albinism, platelet storage dysfunction, and lipofuscin deposits in the reticuloendothelial system. Patients with the disorder are at high risk for major morbidity secondary to bleeding complications. The patient was a 22-year-old military spouse from Puerto Rico with HPS and a history of severe hemorrhage during cesarean delivery of her first child. In this report, we discuss the pathophysiologic features of HPS and the prophylactic administration of 1-deamino-8-arginine-vasopression during labor to minimize blood loss.

Long-lasting breaches in the bladder epithelium lead to storage dysfunction with increase in bladder PGE2 levels in the rat

Increase in bladder mucosal permeability can be reproduced by intravesical administration of protamine sulfate (PS); however, the influence of PS once administered into the bladder disappears within several days. We developed a chronic animal model of urothelial injury using PS. Insertion of a polyethylene catheter through the bladder dome was performed in female Wistar rats. The other end of the catheter was connected to an osmotic pump for continuous delivery of PS or vehicle for 2 wk. Urinary frequency (UF) and voided volume (VV) were measured in the metabolic cage. The fifth group of rats received a high dose of PS (10 mg/ml) for 2 wk and were followed for a further 2 wk without PS. The sixth group received a high dose of PS for 2 wk and loxoprofen (0.1 mg.kg(-1).day(-1)) for 4 wk. UF was increased, and VV was reduced in rats treated with a high dose of PS but not changed in rats treated with a vehicle or a low dose of PS (1 mg/ml). UF was further increased in the fifth group, while unchanged in the sixth group. Histological sections in rats treated with a high dose of PS demonstrated a loss of the upper layer of urothelial cells and an increased number of mast cells. PGE2 level in the bladder was significantly elevated in the fifth group. These results indicate that chronic urotherial injury leads to an increase in UF and a decrease in VV. Increased PGE2 level in the bladder is likely to be associated with long-lasting storage dysfunction.

Lower urinary tract function after intra-arterial chemotherapy with concurrent pelvic radiotherapy for invasive bladder cancer.

Intra-arterial chemotherapy with concurrent pelvic radiotherapy as a bladder-sparing regimen for invasive bladder cancer is highly promising for selected patients. However, lower urinary tract function after this treatment has not been fully investigated. The urodynamic effects of intra-arterial chemotherapy with concurrent pelvic radiotherapy were retrospectively evaluated in 14 patients with organ-confined invasive bladder cancer. The post-treatment urodynamic findings were compared with the pretreatment ones (n = 7), and a comparison was made between the serial urodynamic findings after the treatment in another seven patients who were able to undergo the pretreatment urodynamic study (UDS). The median follow-up period up to the latest UDS was 34 months. Of the 14 patients, the latest UDS revealed some storage dysfunctions in 11 (79%) and some emptying dysfunctions in three (23%). Uninhibited detrusor contraction and decreased bladder compliance were recorded in 29 and 43% at the pretreatment UDS and approximately 50-60 and 20-60% in the serial follow-up studies, respectively (n = 7). Impaired detrusor contractility lasted in one patient. In the seven patients without the pretreatment UDS, decreased maximum cystometric capacity and decreased compliance were recorded in approximately 50-60 and 20-60% at the serial UDS, respectively. Detrusor contractility was aggravated in one patient and completely lost in one with time. The urodynamic findings indicate that the bladder-sparing regimen might result in perpetuating the lower urinary tract dysfunctions due to invasive bladder cancer itself and/or transurethral surgery and might injure the infrasacral autonomic nerves and the bladder itself.

Drug treatment of urinary incontinence

Urinary incontinence is usually classified into four types: stress, urge, reflex and overflow incontinence. The first three types of incontinence are due to urine storage dysfunction and the latter is due to urine emptying dysfunction. To improve urine storage dysfunction treatment should be aimed at decreasing detrusor overactivity, increasing bladder capacity and/or increasing outlet resistance, whereas to improve emptying dysfunction, increasing detrusor contractility and/or decreasing outlet resistance are required. This review summarizes the various drugs currently in clinical use and new drugs under investigation.

The sensitivity of pressure specific bladder volume versus total bladder capacity as a measure of bladder storage dysfunction: E.H. Landau, B.M. Churchill, V.R. Jayanthi, et al. J Urol 152:1578–1581, (November), 1994

The sensitivity of pressure specific bladder volume versus total bladder capacity as a measure of bladder storage dysfunction: E.H. Landau, B.M. Churchill, V.R. Jayanthi, et al. J Urol 152:1578–1581, (November), 1994

The Sensitivity of Pressure Specific Bladder Volume versus Total Bladder Capacity as A Measure of Bladder Storage Dysfunction

Assessment of bladder storage function requires an accurate measure of bladder capacity and pressure. Pressure specific bladder volume is the volume that a bladder can accommodate at a specified pressure. A total of 21 consecutive children with neurogenic bladders who were candidates for bladder augmentation based on standard clinical criteria (upper urinary tract deterioration, incontinence and infection) was studied to determine the efficacy of pressure specific bladder volume as a measure of bladder dysfunction. Urodynamic indexes were compared to previously established nomograms. All 21 patients had bladder volumes at pressures of 30cm. water or less, which decreased below the 5th percentile as determined by the nomogram. In 7 patients (33%) normal total bladder capacity was achieved at the expense of elevated storage pressures. Pressure specific bladder volume provides a better measure of bladder storage function than total bladder capacity because it relates volume to intravesical pressure, does not rely on a subjective end point to bladder filling, and is objective and reproducible.

Augmentation enterocystoplasty for urinary storage dysfunction in females

Urinary incontinence resulting from impaired bladder storage abilities, which is unresponsive to conservative treatments, presents a therapeutic challenge. Carefully selected patients with neurogenic bladder dysfunction, a structurally or anatomically smallcapacity bladder, idiopathic bladder instability, and interstitial cystitis may benefit from augmentation enterocystoplasty. The preoperative evaluation should include a complete assessment of the urinary tract, renal function, and the continence mechanism, along with a careful assessment of urethral accessibility and patency and the patient's willingness and ability to perform lifelong intermittent self-catheterization. Although any segment of bowel is suitable for bladder augmentation, it is advisable to avoid the ileocecal segment in patients with neurogenic bladder dysfunction. The bowel segment should be detubularized and anastomosed to the widely spatulated bladder to avoid an hour-glass deformity. In the immediate postoperative period, patency of the catheter is maintained by frequent, gentle irrigations. Long-term follow-up is mandatory to monitor the chronic bacteriuria and because of the low incidence of spontaneous bladder perforation and carcinogenesis in the augmented bladder.