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In vivo hepatocyte growth factor gene transfer to bladder smooth muscle after bladder outlet obstruction in the rat: a morphometric analysis.

PURPOSE: We determined whether hepatocyte growth factor gene transfer after partial bladder outlet obstruction would prove effective for decreasing transforming growth factor-beta expression and consequently decreasing collagen deposition in partially obstructed rat bladders. MATERIALS AND METHODS: Ten-week-old male Sprague-Dawley rats were divided into 3 groups of 10 each, including group 1--sham operation, group 2--bladder outlet obstruction for 4 weeks and group 3--hepatocyte growth factor gene transfer after bladder outlet obstruction. Two weeks after the onset of bladder outlet obstruction in group 3 hepatocyte growth factor-liposome complex (50 microg human hepatocyte growth factor cDNA) was injected into the smooth muscle of the rats. RESULTS: We noted no difference between groups 2 and 3 with regard to the ratio of bladder weight to body weight. The ratio in groups 2 and 3 was significantly higher than in group 1 (p = 0.043). The mean percent of collagen area +/- SE was 36.32% +/- 1.83%, 27.90% +/- 2.66% and 8.97% +/- 3.35% in groups 1 to 3, respectively (p <0.05). Relative hepatocyte growth factor and c-met mRNA and protein expression were higher in group 3 than in groups 1 and 2. However, the expression of transforming growth factor-beta1 mRNA and protein was higher in group 2 than in groups 1 and 3. CONCLUSIONS: These findings may imply a possible novel therapeutic strategy against bladder dysfunction arising in patients with bladder outlet obstruction.

Animals↗

The effect of bladder outlet obstruction treatment on ultrasound-determined bladder wall thickness.

Detrusor hypertrophy associated with bladder outlet obstruction can be imaged on suprapubic ultrasound, and bladder mass can be quantified from the evaluation of bladder wall thickness and bladder volume. Bladder wall hypertrophy has been found to be correlated with detrusor function. Independent studies have shown that surgical treatment of benign prostatic obstruction results in a significant decrease of bladder mass. Preliminary data suggest the possibility that medical treatment with alpha-adrenergic antagonists might also produce a reduction of bladder wall hypertrophy, although confirmation is still awaited. The development of dedicated automated ultrasound systems for the evaluation of bladder mass might result in the use of such parameters in clinical trials of treatment for benign prostatic hyperplasia and ultimately in daily urologic practice.

Journal Article↗

Giant bladder diverticula causing bladder outlet obstruction in children.

PURPOSE: Congenital giant diverticulum of the bladder is a consequence of deficiency in the detrusor musculature and has been reported in male infants as a rare cause of bladder outlet obstruction. MATERIALS AND METHODS: A 10-year retrospective review revealed 4 patients (3 boys and 1 girl) with bladder outlet obstruction due to a giant bladder diverticulum. Prenatal and postnatal clinical and imaging records were reviewed. RESULTS: Prenatal sonography was unremarkable in all patients. Three males (ages 4 months, 10 months and 3 years) had no medical history of voiding dysfunction, and 1 female (11 years) had the Ehlers-Danlos syndrome. While the girl presented with urinary tract infection, all patients presented with progressively decreasing urinary stream and urinary retention. Each patient underwent voiding cystourethrography (VCUG) and ultrasound. In each patient VCUG showed a giant (greater than 7 cm) bladder diverticulum that descended below the bladder neck and compressed the urethra during voiding. Vesicoureteral reflux was seen in 2 patients. Ultrasonography demonstrated moderate unilateral hydronephrosis in 2 patients. Bladder diverticulectomy was successfully performed in all patients, with ureteral reimplantation in 3. CONCLUSIONS: A giant congenital bladder diverticulum, when noted on VCUG to descend below the bladder neck, may lead to bladder outlet obstruction. To our knowledge we report the first case of a female presenting with bladder outlet obstruction due to a giant bladder diverticulum. Children with connective tissue disorders may be predisposed to this disorder, which must be excluded, regardless of gender, in all patients presenting with voiding abnormalities. Surgical diverticulectomy, often with ureteral reimplantation, is the preferred treatment, with excellent long-term results.

Child↗

Comparison of diagnostic criteria for female bladder outlet obstruction.

PURPOSE: There is no universally accepted definition of bladder outlet obstruction in women. We compared 5 contemporary urodynamic definitions and determined how well they correlated with each other and with clinical suspicion of bladder outlet obstruction. MATERIALS AND METHODS: A total of 154 women who underwent videourodynamics were prospectively evaluated. Clinical obstruction was suspected when history, physical examination, symptoms and basic testing before urodynamics raised the suspicion. Women were classified as having obstruction based on 5 contemporary definitions, including 3 pressure flow cutoff point criteria, videourodynamic criteria and the Blaivas-Groutz nomogram. The McNemar Test was used to compare each definition to the others and to suspicion of clinical obstruction. RESULTS: Of the women 91 were evaluable, including 26 (29%) with obstruction by videourodynamic criteria, 28 (31%) with obstruction by 1998 cut point criteria, 18 (20%) with obstruction by 2000 cut point criteria, 13 (14%) with obstruction by 2004 cut point criteria and 38 (42%) with obstruction by the Blaivas-Groutz nomogram. Videourodynamic and 1998 cut point criteria were not significantly different from each other (78.9% concordance) and each agreed with the clinically obstructed category in the comparison. Compared to the other criteria, the Blaivas-Groutz nomogram overestimated obstruction, while 2004 cut point criteria tended to underestimate it. CONCLUSIONS: Each urodynamic definition of female bladder outlet obstruction has merit. Videourodynamic criteria and 1998 cut point criteria have the highest concordance. The Blaivas-Groutz nomogram overestimates obstruction compared to the other criteria. Therefore, it should not be used as the sole or standard definition of obstruction in women.

Adolescent↗

Enhanced force generation by corpus cavernosum smooth muscle in rabbits with partial bladder outlet obstruction.

PURPOSE: Growing clinical evidence suggests that benign prostatic hyperplasia induced partial bladder outlet obstruction is associated with an increased incidence of erectile dysfunction. We determined whether corpus cavernosum smooth muscle from rabbits with partial bladder outlet obstruction show any molecular or functional differences versus controls. MATERIALS AND METHODS: Force generation and relaxation of corpus cavernosum smooth muscle 2 weeks after partial bladder outlet obstruction by 125 mM. KCl, phenylephrine and field stimulation were determined. Expression of total smooth muscle myosin and alternatively spliced smooth muscle myosin isoforms were determined by reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative competitive RT-PCR, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. Corpus cavernosum smooth muscle from sections of the penis were analyzed morphologically by immunofluorescence microscopy using antibodies to smooth muscle myosin and neurofilament protein. RESULTS: Corpus cavernosum smooth muscle from rabbits with partial bladder outlet obstruction generated 40% to 50% more force than that of sham operated rabbits in response to KCl or phenylephrine and was more difficult to relax. Although quantitative competitive RT-PCR and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that corpus cavernosum smooth muscle from rabbits with partial bladder outlet obstruction expressed only slightly more total smooth muscle myosin at the messenger RNA and protein levels, expression of the high adenosine triphosphatase isoform SM-B increased 2-fold. Morphological examination of corpus cavernosum smooth muscle sections revealed decreased innervation and increased smooth muscle bundle size. CONCLUSIONS: We present the novel finding of molecular and functional changes in the corpus cavernosum smooth muscle associated with partial bladder outlet obstruction. Although the inclusion of sham operation ruled out direct injury during surgery, a change in corpus cavernosum smooth muscle innervation induced by nerve compression by the ligature is likely to induce trophic changes in the corpus cavernosum smooth muscle leading to over expression of the SM-B smooth muscle myosin isoform, increased contractility and impaired relaxation.

Animals↗

Morphological and morphometric analysis of human detrusor mitochondria with urodynamic correlation after partial bladder outlet obstruction.

PURPOSE: We correlated ultrastructural changes in mitochondria in the human detrusor with the severity of partial bladder outlet obstruction on urodynamics. MATERIALS AND METHODS: We recruited into the study 52 men with and without bladder outlet obstruction symptoms. The severity of partial bladder outlet obstruction was determined by pressure flow study. Random detrusor biopsy specimens obtained by cystoscopy were fixed immediately and processed for transmission electron microscopic observation. Random areas were photographed for further morphological and morphometric analysis using mitochondrial damage score and stereological principles. RESULTS: Mitochondrial damage score and mean mitochondrial volume strongly correlated with the urodynamic severity of partial bladder outlet obstruction, while mitochondrial volume density, surface density of the mitochondrial outer membrane and number of mitochondria per unit of cytoplasm area did not significantly correlate with severity. CONCLUSIONS: Detrusor mitochondrial swelling and structural destruction increased with the severity of partial bladder outlet obstruction. These changes may be associated with impaired mitochondrial function and oxidative metabolism after partial bladder outlet obstruction. Detrusor mitochondrial damage may explain voiding dysfunction after partial bladder outlet obstruction develops.

Adult↗

The evolution of detrusor overactivity after watchful waiting, medical therapy and surgery in patients with bladder outlet obstruction.

PURPOSE: We analyzed the evolution of detrusor overactivity in patients with bladder outlet obstruction treated with either medical or surgical therapy or watchful waiting. MATERIALS AND METHODS: Of 255 patients with symptomatic benign prostatic enlargement who completed the International Prostate Symptom Score and underwent full urodynamic investigation 161 presented with bladder outlet obstruction. Of the 161 men 101 were reevaluated with a second clinical evaluation and urodynamics 1 to 5 years (mean 2) after watchful waiting in 20, medical treatment (alfuzosin 20 and finasteride 16) in 36 and surgery (transurethral incision of the prostate 13 and prostatectomy 32) in 45. For statistical analysis Wilcoxon matched paired data and Kruskal Wallis tests were used as appropriate. RESULTS: Overall detrusor overactivity was present in 53 patients (52%) at baseline and 41 (40%) at followup. Detrusor overactivity was present in 9 patients (45%) at baseline and 11 (55%) at followup in the watchful waiting group (p = 0.17); 7 (35%) at baseline and 6 (30%) at followup in the alfuzosin group (p = 0.37); 10 (62.5%) at baseline and 10 at followup in the finasteride group (p = 1); 6 (46%) at baseline and 4 (30%) at followup in the transurethral prostate incision group (p = 0.48); and 21 (68%) at baseline and 10 (31%) at followup in the prostatectomy group (p = 0.02). CONCLUSIONS: Detrusor overactivity is highly prevalent (52%) in patients with bladder outlet obstruction, and appears to persist for long periods when obstruction is left untreated or treated only with medical therapy. However, surgical treatment of bladder outlet obstruction, prostatectomy in particular, significantly reduces the incidence of detrusor overactivity and lessens the chance of its de novo appearance for up to 5 years.

Humans↗

Noninvasive methods of diagnosing bladder outlet obstruction in men. Part 1: Nonurodynamic approach.

PURPOSE: Many methods have been suggested for diagnosing bladder outlet obstruction, as defined by the gold standard of pressure flow studies. Difficulty arises when comparing completely different methods of diagnosing bladder outlet obstruction. A comprehensive review of the literature of the different methods used to diagnose bladder outlet obstruction by noninvasive means was performed with a view to allow such a comparison. MATERIALS AND METHODS: A MEDLINE search was done of the published literature covering until the end of 2004 on noninvasive methods used to diagnose bladder outlet obstruction. A direct comparison of all different methods was made using the sensitivity and specificity, positive predictive value and likelihood ratio of each test. For many of the techniques these values were calculated from the data presented in the article. RESULTS: A multitude of methods has been applied to diagnose bladder outlet obstruction. Broadly the methods were divided into nonurodynamic and noninvasive urodynamic methods. Nonurodynamic methods include symptoms, biochemical tests such as prostate specific antigen, ultrasound derived measurements such as post-void residual urine, bladder weight, prostate configuration and size, intravesical prostatic protrusion and the Doppler resistive index. Part 1 of the review explores and discusses the relative merits of the nonurodynamic based methods. CONCLUSIONS: Ultrasound derived measures such as bladder wall thickness and bladder weight offer a promising possibility of diagnosing bladder outlet obstruction noninvasively. However, further reproducibility and large accuracy studies with better methodological standards are required before they can replace pressure flow studies.

Humans↗

Development of a non-invasive strategy to classify bladder outlet obstruction in male patients with LUTS.

To diagnose bladder outlet obstruction in male patients with lower urinary tract symptoms (LUTS), it is necessary to measure the bladder pressure via a transurethral (or suprapubic) catheter. This procedure incurs some risk of urinary tract infection and urethral trauma and is sometimes painful to the patient. We developed an external condom catheter to measure non-invasively the bladder pressure and developed a strategy to classify bladder outlet obstruction (BOO) based on this measurement. Seventy-five patients with a wide range of urological diagnoses underwent a pressure-flow study followed by a non-invasive study. We tested five different strategies to classify the patients using the provisional International Continence Society (ICS) method for definition of obstruction as the gold standard. Leakage of the external catheter occurred in eight (40%) of the first 20 tested patients. In the remaining 55 patients, only five (9%) of the measurements failed because of leakage. Of the 75 patients, 56 were successfully tested non-invasively. According to the ICS nomogram, the PFS showed that 22 of these patients were non-obstructed, 12 patients were equivocal, and 22 patients were obstructed. Ten of these 56 patients strained, and we found that the relatively high abdominal pressures in these patients were not reflected in the externally measured bladder pressure. Of the remaining 46 patients, 12 of 13 non-obstructed patients and 30 of 33 combined equivocal and obstructed patients could be correctly classified. We developed a simple, non-invasive classification strategy to identify BOO in those male patients who did not strain during voiding.

Catheterization↗

Altered in vitro adrenergic responses of dog detrusor msucle after chronic bladder outlet obstruction.

Muscle strips from the bladder body and dome of normal and control dogs usually demonstrate a relaxing (beta-adrenergic) response to norepinephrine. After bladder outlet obstruction was caused by urethral constriction, all body muscle strips from 7 of 12 dogs (58 per cent) demonstrated contractile (alpha-adrenergic) responses to norepinephrine. Bladder base muscle strips continued to show alpha-adrenergic responses. Desensitization or decreased beta-adrenergic receptor activity may play a part in causing the low compliance and detrusor instability seen in patients with bladder outlet obstruction.

Animals↗

Lipid signaling changes in smooth muscle remodeling associated with partial urinary bladder outlet obstruction.

AIMS: Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth muscle (DSM) reveals altered contractile characteristics. In this study, we analyzed the lipid-dependent signaling system that includes phospholipase A2 in PBOO-induced DSM remodeling and hypertrophy to determine whether the release of arachidonic acid (AA) from phospholipid is altered in the detrusor. METHODS: Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder function was studied by keeping the rabbits in metabolic cages for 24 hr. Bladders were removed from rabbits that had bladder dysfunction (increased urinary frequency and decreased void volume) and the DSM separated from mucosa and serosa. The isolated smooth muscle was incubated with [3H] AA to equilibrate the cytoplasmic AA. The level of AA release was compared with the level obtained with 2-week sham-operated rabbits. RESULTS: The rate of AA release was high in DSM from bladders with PBOO-induced hypertrophy. Carbachol stimulated AA release in control DSM but DSM from obstructed rabbits revealed no further increase from the elevated basal AA release. The half-maximal concentration of carbachol that was required to stimulate AA release from control samples of detrusor was 35 microM. CONCLUSIONS: The increased levels of AA release that are observed in this tissue after PBOO indicate the activation of phospholipase A2. The finding that carbachol could induce contraction, but not an increase in AA, indicates that the carbachol-induced contraction in the obstructed bladders is independent of lipid signaling pathways that involve AA. It is possible that the increased rate of arachidonic acid release from obstructed bladders correlates with the enhanced rates of prostaglandin production reported by other investigators from the same tissue.

Animals↗

Bladder outlet obstruction in the neonate.

Seven neonates with severe bladder outlet obstruction causing urine retention and presenting with a large, palpable lower abdominal mass are reported. The obstruction was due in two cases to posterior urethral valves, in one case each to prune belly syndrome, prolapsing ureterocele, urethral diverticle, and in two cases to pelvic neuroblastoma. Diagnosis was based on physical examination and roentgenographic studies. Therapy and prognosis of bladder outlet obstruction in neonates are discussed. Of the seven patients, 3 neonates died, the rest are developing well.

Female↗

Bladder outlet obstruction after operation for ureterocele.

Two patients with ureterocele-induced bladder outlet obstruction are presented. In each instance, a broad-based diverticulum had developed in the floor of the bladder as a result of the muscular defect created by a simple ureterocele in one patient and an ectopic ureterocele in the other. This bladder diverticulum produced secondary obstruction of the bladder outlet during the act of voiding. Urinary diversion in one patient had been carried out because of bladder outlet obstruction and was being seriously considered in the other patient because of upper tract deterioration. After the correct diagnosis was established, reconstruction of the muscular defect eliminated the obstruction and reestablished satisfactory bladder function. Urinary diversion was thus prevented in one patient and undiversion accomplished in another, when the true obstructing nature of the bladder diverticulum was established and correct therapy instituted.

Child, Preschool↗

Neuroanatomical changes in the rat bladder after bladder outlet obstruction.

OBJECTIVE: To investigate the histological changes in bladder innervation in response to partial bladder outlet obstruction in a rat model. MATERIALS AND METHODS: Forty-eight adult female rats had their bladder outlet partially obstructed by ligating the proximal urethra over a 20 G angiocatheter; 18 shamoperated rats served as controls. Animals were killed after 1, 2 and 4 weeks, and their bladders evaluated using computerized morphometry. Immunohistochemical staining for neuronal protein gene-product 9.5 (PGP, a general neuronal marker) and enzyme histochemical staining of acetylcholinesterase, adrenergic fibres and nitric oxide synthase were performed. RESULTS: Bladder wall changes after obstruction consisted of a six- to sevenfold increase in bladder volume and weight. Smooth muscle hypertrophy was evident equally at all sample times. Cystometry showed functional alterations in bladder capacity and voided pressures; obstructed animals had markedly increased bladder capacities and higher voiding pressures (obstructed, 80-100 cmH2O; normal, 30-40 cmH2O). Neuronal changes in the obstructed bladder were most dramatic within the cholinergic and adrenergic neurotransmitter systems within and surrounding the smooth muscle bundles, where there was less staining than in control animals. PGP immunoreactivity increased slightly. The L-arginine-nitric oxide pathway appeared unperturbed after obstruction. CONCLUSIONS: These histological findings suggest that neuropathic changes in the bladder after outlet obstruction, including detrusor instability, are mainly the result of anatomical perturbations in the cholinergic and adrenergic pathways.

Animals↗

Early molecular changes in bladder hypertrophy due to bladder outlet obstruction.

OBJECTIVES: To determine the temporal relationship between the increase in bladder mass and the expression of growth-associated gene products during bladder hypertrophy due to partial bladder outlet obstruction. METHODS: Adult female rats, subjected to partial bladder outlet obstruction, were killed at defined points, and their bladder weight and total protein were determined and compared with sham-operated and nonoperated controls. Hyperplasia was determined by the expression of proliferating cell nuclear antigen, transcription factors, and cyclins in obstructed rat bladders. Bladder protein was fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and expression of the indicated proteins was determined by Western analysis and immunohistochemistry. RESULTS: The mean bladder weight in sham-operated rats remained at 127 +/- 17 mg, and the weight in the obstructed animals increased to 239 +/- 56 mg at 12 hours, increasing to 486 +/- 168 mg by 168 hours. The total bladder protein increased 1.8-fold after 12 hours and continued to increase for the duration of obstruction. The expression of proliferating cell nuclear antigen in the obstructed group did not begin until 24 hours of obstruction. The expression of the transcription factors, upstream binding factor, and c-Jun followed a similar pattern. Cyclin E and C expression increased most significantly after 48 hours. CONCLUSIONS: Bladder growth after 12 hours of partial outlet obstruction represents cellular hypertrophy based on the increases in bladder weight and total protein accumulation. Cellular hyperplasia occurs after 24 hours of obstruction as represented by increases in transcription factors and cell cycle-specific proteins.

Animals↗

Noninvasive methods of diagnosing bladder outlet obstruction in men. Part 2: Noninvasive urodynamics and combination of measures.

PURPOSE: Many methods have been suggested to diagnose bladder outlet obstruction, as defined by the gold standard of pressure flow studies. Difficulty arises when comparing completely different methods of diagnosing bladder outlet obstruction. A comprehensive review of the literature on the different methods used to diagnose bladder outlet obstruction by noninvasive means was performed with a view to allow such a comparison. MATERIALS AND METHODS: A MEDLINE search was done of the published literature covering until the end of 2004 on noninvasive methods, including single measure and combinations of measures, to diagnose bladder outlet obstruction. A direct comparison of all of the different methods was made using the sensitivity, specificity, likelihood ratio, and pretest and posttest probability of diagnosing bladder outlet obstruction for each test. For many techniques these values were calculated from the data presented in the article. RESULTS: A multitude of methods has been applied to diagnose bladder outlet obstruction. Broadly the methods were divided into nonurodynamic and noninvasive urodynamic methods. Nonurodynamic methods were considered in part 1 of the review. Part 2 considered noninvasive urodynamic techniques, such as uroflowmetry, the penile cuff, the condom method and Doppler urodynamics. A combination of single measures was also considered and the relative merits of these approaches were discussed. CONCLUSIONS: A combination of noninvasive urodynamics and ultrasound derived measures provide promising methods of diagnosing bladder outlet obstruction. However, pressure flow studies still remain the gold standard for assessing bladder outlet obstruction.

Diagnostic Techniques, Urological↗

Endocrine therapy for bladder outlet obstruction from carcinoma of the prostate.

The optimum treatment of bladder outlet obstruction from prostatic cancer is controversial. Although transurethral resection of the prostate may provide immediate relief of the obstruction, there are attendant surgical and anesthetic risks, as well as accumulating clinical evidence to suggest that transurethral resection of the prostate may cause tumor dissemination and diminish patient survival. Orchiectomy, which can be performed safely with local anesthesia, provides definitive endocrine therapy and has been used at our institution in preference to transurethral resection to relieve bladder outlet obstruction from carcinoma of the prostate. There were 35 patients between 51 and 96 years old in urinary retention from carcinoma of the prostate. Patients were treated with orchiectomy and suprapubic or urethral catheter drainage, and subsequently were given voiding trials. If a patient failed to void satisfactorily within 60 days transurethral resection of the prostate was performed. Over-all, 24 of 35 patients (68.6 per cent) were relieved of bladder outlet obstruction by orchiectomy alone. Neither tumor stage nor grade correlated significantly with the response to orchiectomy. We conclude that transurethral resection of the prostate may be held in reserve for patients who do not respond to endocrine therapy or those who do not wish to risk sexual impotence.

Aged↗

Partial bladder outlet obstruction alters Ca2+ sensitivity of force, but not of MLC phosphorylation, in bladder smooth muscle.

Partial bladder outlet obstruction in the rabbit produces changes in bladder function similar to those seen clinically in patients with obstructive uropathies. Whole organ function is significantly altered, as are the smooth muscle cells inside the bladder wall. This study was designed to determine whether outlet obstruction alters smooth muscle function at the level of contractile filaments. Rabbit bladders were partially obstructed for 2 wk. Triton X-100 was used to provide a detergent-skinned bladder smooth muscle preparation that would allow control of the intracellular environment while the ability to shorten and develop force is maintained. Ca2+-force and Ca2+-myosin light chain (MLC) phosphorylation relations and maximal velocity of shortening were determined. The Ca2+ sensitivity of force was significantly lower in tissues from animals subjected to outlet obstruction compared with tissues from control animals. In contrast, no difference was noted in the Ca2+ sensitivity of MLC phosphorylation. Maximal levels of stress and MLC phosphorylation were similar in both animal groups. Maximal velocity of shortening was significantly slower in tissues from outlet-obstructed animals at all Ca2+ concentrations compared with tissues from control animals. Ultrastructurally, detergent skinning had little effect on structural integrity. Moreover, tissues from obstructed animals showed an increase in the number of sarcolemmal attachment plaque structures. We suggest that partial bladder outlet obstruction produces deleterious (e.g., decrease in Ca2+ sensitivity of force) and compensatory (e.g., increase in membrane attachment plaques) changes in bladder smooth muscle cells.

Animals↗