The effect of simulated birth trauma and/or ovariectomy on rodent continence mechanism. Part I: functional and structural change.

PURPOSE: We examined the changes in the lower urinary tract after delivery, intravaginal ballooning and/or ovariectomy. MATERIALS AND METHODS: The study included 10 virgin and 48 primiparous pregnant rats. Cystometry and the stress/sneeze test were performed in virgin and postpartum rats shortly after delivery and at 8 weeks before sacrifice. Half of the delivered animals underwent intravaginal balloon dilation. Four weeks later half in each group underwent ovariectomy. The rats were subdivided into group 1--delivery, group 2--delivery plus balloon inflation, group 3--delivery plus ovariectomy and group 4--delivery plus balloon inflation plus ovariectomy. Tissues from the bladder, bladder neck, urethra and levator were collected, analyzed by electron microscopy, and immunostained for caveolin-1, caveolin-3 and neuronal nitric oxide synthase. RESULTS: Higher bladder capacity was detected in postpartum than in virgin rats. Urine leakage on stress/sneeze testing increased significantly in groups 2 and 4. Electron microscopy revealed a significant decrease in sarcolemma caveolae in the smooth muscle of the bladder and urethra in groups 2 to 4. In the bladder neck in group 3 caveolae were increased in smooth muscle. In groups 2 to 4 in the smooth muscle of the bladder and urethra caveolin-1 was significantly decreased. Caveolin-3 and neuronal nitric oxide synthase in striated muscle also significantly decreased in groups 2 to 4. CONCLUSIONS: These findings suggest that birth trauma simulated by ballooning and ovariectomy may contribute to stress urinary incontinence. The alteration in smooth muscle caveolae as well as the membrane protein caveolin may have a role in functional alterations caused by birth trauma and ovariectomy.

Low urethral pressure profile--clinical implications.

The clinical impact of urethral pressure profilometry (UPP) has been a main urological topic over the past three decades. Exaggerated expectations and differing techniques with incongruent results caused a controversial appearance. However, since the UPP is the only method to measure directly aspects of the urethral closure function, all types of sphincteric urinary incontinence represent indications for this measurement. Based on long-term experience this paper aims to discuss the various complexes regarding the urethral pressure profilometry. The significance of the urethral closure function for urinary continence and the urodynamic relevance of active and passive pressure transmission are described. In addition, clinical implications in terms of therapeutic strategies to treat urinary stress incontinence with regards to a low urethral pressure profile are presented.

Sacral neurostimulation and neuromodulation in urological practice.

The problems associated with treating various forms of lower tract dysfunction by electrical stimulation are reflected in the many years of basic and clinical research in this area. However, better understanding of both neuroanatomy and neurophysiology, and development of new technologies have led to further application of electrical current to restore impaired bladder function. Contemporary knowledge of the potential for both sacral neurostimulation and neuromodulation as a therapeutic option for lower urinary tract dysfunction is reviewed.

Surgical treatment of interstitial cystitis in women.

Interstitial cystitis is a clinical entity that has been known for a century, but its pathophysiology remains largely unknown and the optimal treatment is a matter of ongoing discussion. A successful strategy for treatment relies on precise appraisal of symptoms, clinical findings and histology, as well as on the patient's individual personality. The least invasive treatment possible should be chosen, and only after conservative options have been exhausted should a surgical solution be considered. In this respect, anatomical bladder capacity plays an important role. A large capacity indicates the potential for conservative treatment and may be regarded as a negative predictor for the outcome of orthotopic bladder substitution. In contrast, a small anatomical capacity is unlikely to respond to conservative therapy, but is associated with a high probability of successful orthotopic bladder substitution.

Sacral neuromodulation for treatment of lower urinary tract dysfunction.

Despite initial reservations, sacral neuromodulation has begun to develop as a new therapeutic tool for the treatment of lower urinary tract dysfunction. It bridges the gap between conservative treatment options and highly invasive procedures, such as urinary diversion. At present, there are no clinical variables that can reliably predict the efficacy of neuromodulation in an individual patient. All patients, regardless of indication, must therefore undergo a test stimulation before they can be offered chronic sacral neuromodulation with an implanted system. Evaluations in various clinical trials have confirmed that sacral neuromodulation, based on unilateral sacral foramen electrode implantation, has statistically significant therapeutic effects compared to controls, in patients with urge syndromes and failure to empty. The patients most likely to benefit from this treatment are those with detrusor hyperactivity or detrusor hypo-activity. Those with pain syndromes are less likely to respond and to benefit from treatment. Acute and subchronic sacral neuromodulation are associated with very low rates of complications. Complications of chronic sacral neuromodulation are caused either by surgery-related morbidity or hardware problems. Conservative treatment options should be exhausted before neuromodulation is considered. This rule has two purposes: First, it postpones surgery, with its potential morbidity, for as long as possible; second, the long-term efficacy of neuromodulation is still unclear and may be limited in some patients. A fully exploited conservative therapy, in combination with subsequent sacral neuromodulation, may therefore be the optimum way to pursue therapeutic options of relatively low invasiveness.

An unusual case of ureteral ectopia in the seminal vesicle: diagnosis and surgical management.

We report the case of a young man who presented with numerous episodes of ipsilateral epididymitis. Selected imaging studies with consideration of urogenital embryology lead to the rare diagnosis of a dysplastic kidney with ureteral ectopia in the seminal vesicle. After nephroureterectomy and vesiculectomy, convalescence was uneventful. No specific symptoms, equivocal diagnostic findings and the small number of patients limit the surgical experience in diseases of the seminal vesicle. Suprainguinal extravesical extirpation, however, appears to be an excellent operative approach in cases of unilateral seminal vesicle cysts.

Bladder acellular matrix graft: in vivo functional properties of the regenerated rat bladder.

The purpose of this study was to determine whether the rat urinary bladder augmented by an acellular matrix graft can restore the bladder's low-pressure reservoir function and preserve normal micturition. After partial cystectomy (> 50%) and grafting with the bladder acellular matrix graft (BAMG), storage and voiding functions were monitored in 20 rats by means of a specially designed "micturition cage," leak-point cystography, and cystometry. After 4 months, sections (n = 6) were examined histologically to evaluate regeneration of bladder wall components within the BAMG. Bladder capacity and compliance increased progressively and were significantly higher in the grafted animals than in controls (partial cystectomy only), and volumes per void were significantly higher than in either control or normal animals. At 4 months, the regenerated urothelium, smooth muscle, blood vessels and nerves within the BAMG were qualitatively identical to normal bladder wall. Augmentation cystoplasty with the homologous BAMG leads to morphologic and functional rat bladder regeneration, thus enhancing low-pressure reservoir function and preserving normal micturition.

Retrovesical mass in men: pitfalls of differential diagnosis.

PURPOSE: We review the differential diagnosis and treatment of retrovesical masses in men. MATERIALS AND METHODS: During the last 8 years 21 male patients 3 to 79 years old (mean age 47.1) presented with symptoms or signs of a retrovesical mass. Clinical features and diagnostic findings were reviewed, and related to surgical and histopathological findings. RESULTS: The retrovesical masses included prostatic utricle cyst in 3 cases, prostatic abscess in 1, seminal vesicle hydrops in 6, seminal vesicle cyst in 2, seminal vesicle empyema in 3, large ectopic ureterocele in 1, myxoid liposarcoma in 1, malignant fibrous histiocytoma in 1, fibrous fossa obturatoria cyst in 1, hemangiopericytoma in 1 and leiomyosarcoma in 1. In 17 patients various symptoms were seen and in 4 the mass was incidentally detected. A mass was palpable on digital rectal examination in 16 cases and visible on sonography in 20. For a cystic mass medial location relative to the bladder neck was suggestive of prostatic abscess or utricle cyst, while lateral location was suggestive of seminal vesicle cyst/hydrops or empyema, ectopic ureter or ureterocele. In 6 patients diagnosis was established only by exploratory laparotomy and histopathological examination. CONCLUSIONS: Digital rectal examination and sonography reliably detect a retrovesical mass. Nevertheless, clinical signs and median or lateral location relative to the bladder neck on ultrasound are diagnostic only for cystic lesions. Computerized tomography and magnetic resonance imaging are useful for staging malignant tumors. However, needle or open biopsy is required in most cases to establish a histopathological diagnosis. Exploratory laparotomy and histopathological examination are the procedures of choice when other findings are equivocal.

The impact of sacral root anatomy on selective electrical stimulation for bladder evacuation.

Although different structures have been studied with electrostimulation to elicit bladder evacuation, only the sacral root remains feasible for clinical application at present. However, the resultant concomitant contractions of the bladder and sphincteric muscles have been the principal problem over the last few decades. Attempts to identify fibers within the sacral ventral root that innervate the detrusor predominantly have been made by microsurgery alone or in combination with advanced electrical blocking techniques. This article evaluates our past and present efforts to achieve voiding in light of the mixed nature of sacral root anatomy.

Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human.

OBJECTIVE: To compare the composition and mechanical properties of the newly developed bladder acellular matrix graft (BAMG) with the normal urinary bladder in rat, pig and human. MATERIALS AND METHODS: Rat, pig and human urinary bladders were harvested and divided into control and experimental groups. For the latter, BAMGs were prepared, and light and transmission electron microscopic studies performed. Strips from the normal bladders and the BAMGs (10 in each group) were tested under tension, and the ultimate tensile strength, maximum strain, and elastic modulus were determined from stress/strain curves. RESULTS: Both types I and III collagen, as well as elastic fibres, were observed as major components of the matrix scaffold. There were more collagen type I fibres in the rat than in the pig and human BAMGs, whereas the pig, and particularly the human, both showed higher levels of type III collagen and elastic fibres. These different matrix scaffold patterns were confirmed by electron microscopy. Results from biomechanical testing showed no significant differences for strength, strain or elastic modulus between BAMG and control bladder strips, except in the rat where the maximum strain values were significantly lower. CONCLUSION: There are variations in the acellular matrix structure with similar biomechanical properties between the BAMG and the normal urinary bladder in three different species. These results may underscore the potential of the BAMG. Furthermore, this in vitro model provides a suitable method to study the mechanical properties of the urinary bladder and may serve as a diagnostic tool for various investigations.

Functional rat bladder regeneration through xenotransplantation of the bladder acellular matrix graft.

OBJECTIVE: To determine the decreased antigenicity of the bladder acellular matrix graft (BAMG) through xenotransplantation and to assess the in vivo and in vitro functional properties of the rat urinary bladder thus regenerated. MATERIALS AND METHODS: After partial cystectomy (> 50%), BAMGs prepared from hamster, rabbit and dog urinary bladders were grafted to male and female Sprague-Dawley rats; 10 control rats underwent partial cystectomy only. Urinary storage and voiding function were monitored in 15 animals using a specially designed 'micturition cage' and cystometry. After 4 months, organ-bath studies and histological techniques were used to evaluate bladder regeneration in vitro in the grafted animals. RESULTS: Clinically relevant antigenicity was not evident; no animal died from rejection and all bladder wall components regenerated in all BAMG xenografts. However, the degree and quality of regeneration varied. Muscularization, peak pressure, and bladder capacity were higher in the hamster BAMG-grafted animals, whereas in vitro contractility and compliance were best in the dog BAMG-regenerated bladders. All grafted bladders had significantly better capacity and compliance than the autoregenerated bladders after partial cystectomy alone. CONCLUSIONS: The present in vivo and in vitro studies show that BAMG-augmentation cystoplasty can lead to morphological and functional regeneration of the rat bladder, preserving its low-pressure reservoir function. Because BAMG-regenerated bladders show functional innervation that is similar to normal bladders, they can work in coordination with the host bladder components, thus generating adequate intravesical pressure to produce sustained voiding. The decreased antigenicity makes heterologous BAMG transplants feasible without immunosuppression.

In vitro functional properties of the rat bladder regenerated by the bladder acellular matrix graft.

PURPOSE: To assess the response of rat urinary bladder regenerated by the homologous bladder acellular matrix graft (BAMG) to in vitro electrical and pharmacologic stimuli. MATERIALS AND METHODS: In Sprague-Dawley rats, partial cystectomy (>50%) was performed, followed by BAMG augmentation cystoplasty. After 4 months, organ bath studies of tissue strips in 10 were used to compare the contractility of the BAMG regenerates and the corresponding host detrusor smooth muscle. RESULTS: The BAMG regenerates exhibited contractile activity to electrical field stimulation and a qualitatively identical pattern of response to muscarinic, purinergic, alpha- and beta-adrenergic drug administration and nitric oxide. At 4 months after surgery, the maximum forces of contraction of the BAMG regenerates to carbachol stimulation amounted to close to 80% of the host bladder response. With electrical field stimulation, they equaled 44% and 62% of the host bladder response after 2.5 and 4 months, respectively. Histological and immunohistochemical studies confirmed the presence of receptors for neurotransmitters that these functional in vitro studies implied. CONCLUSIONS: The present study provides further evidence that augmentation cystoplasty with the BAMG leads to functional regeneration of the rat bladder detrusor smooth muscle.

Bladder acellular matrix graft in rats: its neurophysiologic properties and mRNA expression of growth factors TGF-alpha and TGF-beta.

To assess the neurophysiologic properties and molecular mechanisms of the bladder acellular matrix graft (BAMG), we performed cystometric and neurophysiologic studies in male Sprague-Dawley rats (n = 46) at varying intervals. The animals were assigned to 3 groups: 1) normal, 2) partial cystectomy (>50%), and 3) partial cystectomy (>50%) and grafting with a BAMG of equal size. Additionally, matrix-grafted and host bladders were processed for analysis of mRNA expression of transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, and TGF-beta3 by reverse transcriptase polymerase chain reaction. Matrix-grafted bladders showed a significantly higher bladder capacity at 3 and 6 weeks and 4 months than those with partial cystectomy alone, and a significantly higher bladder capacity at 4 months than in normal controls (P < or = 0.01). Residual urine volume was significantly increased at 4 months. Electrostimulation of the pelvic nerve provoked generalized bladder contractions, a response that was reduced by atropine and hexamethonium. Variable induction of TGF-alpha, TGF-beta1, TGF-beta2, and TGF-beta3 gene transcription was evident in the BAMG, with prominent mRNA expression of TGF-alpha and TGF-beta1 6 months after surgery. These cystometric results and detrusor responses to stimulation provide further evidence that graft components do not interfere with host components. Matrix-grafted rat bladders generate, although not increased over time, adequate intravesical pressure responses to produce sustained voiding. Gene expression of different growth factors may be significant in understanding their role in the development and differentiation of the BAMG for partial bladder replacement.

Treatment of interstitial cystitis: comparison of subtrigonal and supratrigonal cystectomy combined with orthotopic bladder substitution.

PURPOSE: We retrospectively evaluate the outcome of interstitial cystitis treated with subtrigonal or supratrigonal cystectomy and orthotopic bladder substitution. MATERIALS AND METHODS: Of 22 women and 1 man a mean of 51 years old with interstitial cystitis refractory to conservative therapy 17 were treated with subtrigonal cystectomy and ureteral reimplantation (group 1), and 6 were treated with supratrigonal cystectomy directly above the ureteral orifices (group 2). Both groups underwent orthotopic bladder substitution with an ileocecal pouch (Mainz pouch I). RESULTS: Postoperatively functional capacity significantly increased from a mean plus or minus standard error of mean 46 +/- 5 to 346 +/- 57 ml. in group 1 and 34 +/- 61 to 319 +/- 29 ml. in group 2 (p < 0.001). Daytime and nighttime urinary frequency significantly decreased from 24 +/- 2 to 8 +/- 1 and 7 +/- 1 to 2 +/- 1 ml., respectively, in group 1 and 28 +/- 2 to 6 +/- 1 and 6 +/- 1 to 1 +/- 1 ml., respectively, in group 2 (p < 0.001). At a mean followup of 93.9 months 14 patients in group 1 (82%) are completely symptom-free, and 1 has tolerable residual urinary urgency and suprapubic pain. At a mean followup of 31.5 months all group 2 patients are symptom-free and void spontaneously, whereas 41% of the group 1 patients require self-catheterization after subtrigonal cystectomy. CONCLUSIONS: For interstitial cystitis refractory to conservative treatment subtotal cystectomy with orthotopic bladder substitution with the ileocecal pouch (Mainz pouch I) is a valid therapeutic option. In this series supratrigonal and subtrigonal cystectomy resulted in similar relief of symptoms but the former appears to provide better functional bladder rehabilitation.

Free ureteral replacement in rats: regeneration of ureteral wall components in the acellular matrix graft.

OBJECTIVES: To evaluate ureteral replacement by a free homologous graft of acellular matrix in a rat model. METHODS: In 30 male Sprague-Dawley rats, a 0.3 to 0.8-cm midsegment of the left ureter was resected and replaced with an acellular matrix graft of equal length placed on a polyethylene stent. The animals were killed at varying intervals, and the grafted specimens were prepared for light and electron microscopy. RESULTS: In all animals, the acellular matrix graft remained in its original position without evidence of incrustation or infection, and histologic examination showed complete epithelialization and progressive infiltration by vessels. At 10 weeks, smooth muscle fibers were observed; at 12 weeks, nerve fibers were first detected; at 4 months, smooth muscle cells had assumed regular configuration. CONCLUSIONS: The ureteral acellular matrix graft appears to promote the regeneration of all ureteral wall components.

Appendix carcinoma invading the urinary bladder.

We report a case of an appendix carcinoma invading the urinary bladder. In contrast to other bowel tumors invading the bladder, history and symptoms were consistent with a primary bladder tumor. This is due to the unique anatomical position of the appendix where the tumor did not hinder passage of bowel contents or cause melena. Findings on physical examination as well as diagnostic imaging and transurethral resection were inconclusive. Consideration of local progression of an appendix carcinoma is an important differential diagnosis. In contrast to other vesical or extravesical T4 tumors, the appendix carcinoma offers a good chance for resection en bloc by right-sided hemicolectomy and partial cystectomy.