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Differences in bladder compliance with time and associations of bladder management with compliance in spinal cord injured patients.

PURPOSE: Controversy continues on the optimal method of bladder management in spinal cord injured patients. We investigated the effects of bladder management on bladder compliance and changes in compliance with time. MATERIALS AND METHODS: We retrospectively reviewed the charts, and video urodynamic and upper tract radiographic studies of 316 patients with spinal cord injury. Patients were categorized according to interval since injury and bladder management method, including clean intermittent catheterization, spontaneous voiding and chronic Foley catheterization. Those with upper tract complications were compared with asymptomatic controls at the bladder compliance threshold values of 10.0, 12.5, 15.0 and 20.0 cc/cm. water. RESULTS: No significant differences were noted among bladder management method groups for followup, level, completeness or mechanism of injury. A bladder compliance threshold of 12.5 cc/cm. water was selected for the remaining comparisons based on the frequency of complications compared with asymptomatic controls. Patients using intermittent catheterization had a significantly higher incidence of normal compliance than the Foley management group for suprasacral, complete and incomplete injury (p<0.01). Normal bladder compliance was more common in patients with suprasacral than sacral and incomplete than complete spinal cord injury for each bladder management type. Logistic regression analysis of compliance versus bladder management and age of injury (interval since injury) revealed that intermittent catheterization and spontaneous voiding were associated more with normal compliance than Foley catheterization (RR = 9.2, 5.4 and 1.0, respectively). Combined data showed that each successively older age of injury cohort was at 23% greater risk for loss of normal compliance than the preceding cohort. Low compliance was statistically associated with vesicoureteral reflux, radiographic upper tract abnormality, pyelonephritis and upper tract stones (p<0.01, <0.01, 0.04 and <0.01, respectively). CONCLUSIONS: Clean intermittent catheterization protects bladder compliance in spinal cord injured patients regardless of the level or completeness of injury and helps to prevent low compliance with time. Also, in the population studied low compliance was associated with upper tract complications. Therefore, clean intermittent catheterization is the superior method for preserving bladder compliance and preventing the upper tract complications associated with low compliance.

Adult↗

[Clinical evaluation of urinary NMP22 (nuclear matrix protein 22) bladder chek in the detection of patients with bladder cancer].

The clinical usefulness of the nuclear matrix protein 22 (NMP22) Bladder Chek test as a novel urine marker in the detection of patients with bladder cancer was evaluated in comparison with the urinary NMP22 enzyme-linked immunosorbent assay (ELISA) and urinary cytology. A total of 40 patients with pathologically proven bladder cancer voided urine specimen before treatment. The urine samples were divided for NMP22 Bladder Chek test, NMP22 ELISA, and urinary cytology. In the 40 patients with bladder cancer, the overall positive rate was 62.5% for the NMP22 Bladder Chek test, 55% for the NMP22 ELISA test, and 27.5% for urine cytology. There was a significant difference between NMP22 Bladder Chek, NMP22 ELISA and cytology. The positive rate with the NMP22 Bladder Chek and NMP22 ELISA was higher in the patients with high grade and large-size (1 cm < or =) tumor. In 40 patients presenting with microhematuria without urothelial cancer, the false positive rate 12.5, 10, and 0% for NMP22 Bladder Chek, NMP22 ELISA, and urinary cytology. No significant difference was found with the test. In conclusion, the urine NMP22 Bladder Chek test provided a higher positive rate than the NMP22 ELISA test and urinary cytology. Therefore, the NMP22 Bladder Chek test may be clinically more useful as a tumor marker for the diagnosis of bladder cancer.

Adult↗

The clinical significance of the reflux producing intrinsic bladder pressure and bladder volume in reflux and reflux nephropathy.

In 60 patients with vesicoureteral reflux (VUR) primarily diagnosed on a conventional voiding cystourethrography, the VUR was revisited more precisely by way of a video pressure flow VCU via suprapubic catheters with special emphasis on the reflux producing intrinsic bladder pressure (RPBP) and the reflux producing bladder volume (RPBV). The VUR was subdivided into a low pressure reflux group (RPBP less than or equal to 35 cm H2O) and a high pressure reflux group (RPBP greater than 35 cm H2O), and into a low bladder volume reflux group (RPBV less than or equal to 50% of bladder capacity or 150 ml) and a high bladder volume reflux group (RPBV greater than 50% of bladder capacity or 150 ml). Reflux grade II or less was defined as low grade reflux and reflux higher than grade II was defined as high grade reflux. Thirty-three units refluxed at low pressures and 17 units at high pressures. In 33 units the reflux occurred at a low bladder volume and 17 at a high bladder volume. The pressure at the reflux was equally distributed in the low and the high grade reflux group. However, in the high grade reflux group low pressure, low bladder volume reflux was accompanied by a significantly higher incidence of nephropathy compared to the high pressure high volume reflux group. Furthermore, the low volume reflux group showed a significantly higher incidence of nephropathy compared to the high bladder volume reflux group. This report substantiates the coincidence between severity of reflux nephropathy and exposure to reflux and stresses the importance of a thorough evaluation of VUR patients including measurement of the reflux producing intrinsic bladder pressure and bladder volume.

Adolescent↗

Xenon-133 resorption in urinary bladder: functional diagnosis of bladder epithelium.

The examination of resorption from the urinary bladder had previously been restricted almost exclusively to animal research, since, as a rule, a separation of the bladder from the urinary tract is required. If this is not done, the resorbed test substance quickly finds its way back into the bladder. More than 95 per cent of the xenon which has been resorbed from the bladder becomes eliminated through the lungs. The detection and measurement of xenon in the exhaled air enables one to conduct, in a relatively simple fashion, urinary bladder resorption research using human subjects. Studies based on 141 patients showed that the xenon exhalation tests currently represent the most sensitive and exact method for detecting and determining the nature of inflammatory diseases of the urinary bladder. With a number of so-called "irritable bladder" cases it became clear that functional disorders of the bladder epithelium could be present without any evidence of associated morphologic changes. With radiogenic treatment of tumors in the lower pelvic region one experiences an increase in bladder resorption with increased exposure to radiation. There exists, as it were, a linear correlation between the radiation dosage and the degree of resorption from the urinary bladder. Three months after terminating radiotherapy one can detect, as a rule, only a negligible increase in resorption. If at this time the rate of xenon resorption still remains clearly high, one must reckon with permanent radiation damage of the bladder, insofar as it proves unsuccessful to eliminate the cause of cystitis.

Cystitis↗

Flow cytometric study comparing paired bladder washing and voided urine for bladder cancer detection.

Paired bladder washings and voided urines from bladder cancer patients were compared as sources of exfoliated cells for detection of bladder carcinoma by flow cytometry (FCM). Bladder specimens fixed in 25% ethanol within sixty minutes of collection were found to be superior to unfixed bladder specimens. The percentage of specimens with good DNA resolution was greater for bladder washings (67% unfixed, 90% fixed) than voided urines (41% unfixed, 66% fixed). There was no difference in DNA resolution between specimens that remained unfixed less than one day, one day, or two days suggesting that the cells undergo the majority of degradation within a critical period soon after collection. Once fixed, there was no difference in DNA resolution for up to nineteen days, which suggests the feasibility of specimen transport to central FCM laboratories. Eighteen percent of unfixed bladder washings and 33 percent of unfixed voided urine specimens contained an insufficient number of cells (less than 5,000) at the time of analysis compared with 6 percent bladder washings and 17 percent voided urines fixed in 25% ethanol. Flow cytometry and cytology results were concordant in 28/43 (65%) of fixed bladder washings and 9/13 (69%) of fixed voided urine. Voided urine was unreliable in providing consistent FCM data due to the high number of specimens with poor resolution or insufficient cells and is not recommended as a substitute for bladder washing when screening high-risk populations or monitoring patients with past history of bladder cancer.

Carcinoma, Transitional Cell↗

Pharmacological characterization of urinary bladder smooth muscle contractility following partial bladder outlet obstruction in pigs.

Partial bladder outlet obstruction of the pig is considered as a valuable preclinical model for evaluating the profile of compounds for the treatment of bladder overactivity. In this study, we characterized the pharmacological properties of isolated bladder smooth muscle from pigs following partial outlet obstruction and its sensitivity to potassium channel openers. Bladder strips from obstructed animals showed significantly lower maximal efficacy (E(max)) and sensitivity to stimulation by ATP and carbachol, but not to those evoked by serotonin, compared to age-matched controls. Tissue strips from obstructed animals also showed a 2.5-fold increase in the potency and significantly reduced maximum response following K+ depolarization. With respect to spontaneous activity, bladder strips from control strips demonstrated little spontaneous phasic activity at all preloads examined. In contrast, bladder strips from obstructed animals showed large preload-dependent increases in spontaneous phasic activity at preload values of 16-32 g. The potencies of K(ATP) channel openers to relax carbachol-evoked contractions showed a good 1:1 correlation (r(2)=0.90) between obstructed and control bladder strips. These studies demonstrate that obstructed pig bladders show enhanced spontaneous phasic activity especially at elevated preloads, which may underlie unstable myogenic bladder contractions reported in cystometrographic measurements in vivo. The impaired responses to electrical field stimulation could be attributed to reduced efficacies and/or lower sensitivities of muscarinic and purinergic signaling pathways. K(ATP) channel sensitivities remain essentially unimpaired in the obstructed bladder and could be effectively modulated by openers with potential for the treatment of overactive bladder secondary to outlet obstruction.

Adenosine Triphosphate↗

Routine bladder biopsies in men with bladder outlet obstruction?

OBJECTIVES: To establish whether routine evaluation of light microscopic changes in bladder biopsies in men with graded bladder outlet obstruction correlates with urodynamic parameters and to evaluate the performance of two pathologists in bladder biopsy interpretation. METHODS: In 63 consecutive patients presenting with lower urinary tract symptoms suggestive of bladder outlet obstruction, the workup included bladder biopsies, which were semiquantitatively and independently evaluated by two pathologists for fibrosis, elastosis, muscle cell degeneration, inflammation, and additional remarkable findings. Furthermore, as determined by their general impression, the pathologists gave a diagnosis of normal or graded abnormality. The pathologists' performance was compared and the clinical and urodynamic data were correlated to the consensus histologic diagnoses. RESULTS: Fifty-four of 63 cases could be evaluated. The intraobserver and interobserver reproducibility were reasonable, with a kappa of 0.35 and 0.50, respectively. The consensus diagnosis of abnormal bladder biopsy correlated with impaired bladder compliance and capacity. However, no correlation was found between the presence and severity of histologic abnormalities and Schäfer class, urethral resistance factor, instability, postvoid residual urine volume, symptom score, and prostate volume. CONCLUSIONS: Although abnormal bladder biopsies correlated significantly with impaired bladder capacity and compliance, routine evaluation of bladder biopsies is not indicated in the evaluation of bladder outlet obstruction.

Biopsy↗

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↗

Partial outlet obstruction of the rat bladder induces a stimulatory response on proliferation of the bladder smooth muscle cells.

Outlet obstruction of the rat bladder induces hypertrophy/hyperplasia characterized by increases in bladder mass, smooth muscle content, and collagen deposition. In order to understand the mechanism of the outlet obstruction-induced hypertrophy and hyperplasia, we first determined the temporal pattern of changes in bladder mass after inducing the outlet obstruction. Histological analysis revealed that the smooth muscle cells with hypertrophy and hyperplasia, fibroblasts and connective tissue were increased in a time-dependent manner, corresponding to the temporal pattern observed in the changes in bladder mass, although the phase of changes in these tissue components was somewhat different. In order to further determine whether any proliferation-stimulatory factors were released from the bladder with obstruction in correspondence with increased bladder mass, soluble fractions were prepared from the bladders with outlet obstruction for 3-30 weeks, and their effects on proliferation of smooth muscle cells were examined. The soluble fractions prepared from the bladders at 3 to 14 weeks after obstruction slightly but significantly facilitated the proliferation of cultured smooth muscle cells, while the soluble fractions released after 20 weeks rather suppressed the proliferation. These results suggest that the initial increase in bladder mass might be in part due to the facilitated proliferation of smooth muscle cells of the bladder body induced by growth factors released into the soluble fractions, and that hypertrophy might then play a role in the increased bladder mass at later phases.

Animals↗

Prostaglandins and cyclic nucleotides in the urinary bladder of a rabbit model of partial bladder outlet obstruction.

Bladder outlet obstruction (BOO) is a common disorder that is associated with altered bladder structure and function. For example, it is well established that BOO results in hypertrophy and hyperplasia of the bladder smooth muscle as well as detrusor instability. Since prostaglandins (PGs) and cyclic nucleotides (cyclic AMP [cAMP] and cyclic GMP [cGMP]) mediate both smooth muscle tone and proliferation, it is reasonable to suggest that changes in their levels may be involved in the pathophysiology of BOO-associated bladder disorders. Hence, the objective of this study was to investigate cyclic AMP, cyclic GMP and prostaglandins in the bladder of a rabbit model of BOO. BOO was induced in adult male New Zealand White rabbits. After 3 weeks, urinary bladders were excised, weighed and cut into segments. They were then incubated with stimulators of PGs, cAMP and cGMP and the formation of PGs, cAMP and cGMP were measured using radioimmunoassays. There was a significant increase in the obstructed bladder weights (P=0.002). The formation of PGE2, PGI2, cAMP and cGMP was significantly diminished in the detrusor (P<0.05) and bladder neck (P<0.05) in the BOO bladders compared to age-matched controls. Since PGE2, PGI2, cAMP and cGMP are known to inhibit the proliferation of smooth muscle cells (SMCs), the decreased synthesis of these factors, in BOO, may play a role in bladder SMC hypertrophy/hyperplasia. Our study points to the possible use of drugs that modulate the NO-cGMP and/or PG-cAMP axes in BOO-associated bladder pathology.

Acetylcholine↗

[Efficacy and problems of bladder volume measurement using portable three dimensional ultrasound scanning device--in particular, on measuring bladder volume lower than 100ml].

OBJECTIVES: Using a portable three dimensional ultrasound scanning device (The Bladder Scan BVI6100, Diagnostic Ultrasound Corporation), we examined measured values of bladder volume, especially focusing on volume lower than 100 ml. MATERIALS AND METHODS: A total of 100 patients (male: 66, female: 34) were enrolled in the study. We made a comparison study between the measured value (the average of three measurements of bladder urine volume after a trial in male and female modes) using BVI6100, and the actual measured value of the sample obtained by urethral catheterization in each patient. We examined the factors which could increase the error rate. We also introduced the effective techniques to reduce measurement errors. RESULTS: The actual measured values in all patients correlated well with the average value of three measurements after a trial in a male mode of the BVI6100. The correlation coefficient was 0.887, the error rate was--4.6 +/- 24.5%, and the average coefficient of variation was 15.2. It was observed that the measurement result using the BVI6100 is influenced by patient side factors (extracted edges between bladder wall and urine, thickened bladder wall, irregular bladder wall, flattened rate of bladder, mistaking prostate for bladder in male, mistaking bladder for uterus in a female mode, etc.) or examiner side factors (angle between BVI and abdominal wall, compatibility between abdominal wall and ultrasound probe, controlling deflection while using probe, etc). CONCLUSIONS: When appropriate patients are chosen and proper measurement is performed, BVI6100 provides significantly higher accuracy in determining bladder volume, compared with existing abdominal ultrasound methods. BVI6100 is a convenient and extremely effective device also for the measurement of bladder urine over 100 ml.

Aged↗

[Three cases of transitional cell carcinoma in bladder diverticulum treated by a bladder-preserving approach].

Three cases of transitional cell carcinoma (TCC) in the urinary bladder diverticulum were encountered during a period of 12 years and bladder preserving treatments were performed. Case 1: A 78-year-old man was admitted with a chief complaint of hematuria. Papillary tumors in the diverticulum of the right bladder wall were revealed (TCC, G3, T3N0M0). Intraarterial infusion chemotherapy was performed and complete remission was achieved. When a recurrent bladder tumor appeared 22 months later, transurethral resection was performed and there was no evidence of recurrence for 50 months. Case 2: A 60-year-old man was admitted with a chief complaint of gross hematuria. Cystoscopic examination revealed papillary tumors in a bladder diverticulum near the ureteral left orifice. Transurethral resection revealed TCC G2 and carcinoma in situ. Partial cystectomy, including the bladder diverticulum, and vesicoureteral neostomy was performed. The histological stage of the tumor was pTis and the wall of diverticulum possessed a thin muscle layer histopathologically. Twenty two months later, recurrence in the left bladder wall developed and transurethral resection and bladder instillation therapy were performed. For 21 months he had no evidence of recurrence. Case 3: A 59-year-old man was admitted with a chief complaint of hematuria. A solid tumor in the diverticulum of the bladder left wall was revealed. After 4 courses of intraarterial infusion chemotherapy, 41% remission was achieved and partial cystectomy was performed. Histopathological diagnosis was TCC G3, pT3b, INF-alpha, v (-), ly (-), and no muscle layer was found in the diverticulum. There was no evidence of recurrence 16 months after operation. By using the combination therapy, bladder preserving treatment is possible in the cases of bladder cancer arising in the diverticulum.

Aged↗

Comparison of telomerase activity in bladder carcinoma and exfoliated cells collected in urine and bladder washings, using a quantitative assay.

Telomerase activity was measured with a quantitative assay, based on a modification of telomeric repeat amplification protocol method, in bladder cancers and apparently normal mucosa in 33 patients. In the same patients, the enzyme was also measured in exfoliated cells collected both with voided urine and bladder washings. Results obtained in urine were compared with those from 20 healthy subjects. Telomerase activity was present in 31 (94%) bladder cancer tissues and in 23 (72%) apparently normal mucosa samples. However, the levels of enzyme activity were significantly higher in cancer tissues in comparison with normal mucosa (mean +/- SD, 47.3 +/- 23.2 and 14.9 +/- 6.1 ng DNA/microg protein, respectively; P < 0.0001). Telomerase activity in bladder cancer tissues was not related to tumor stage and grade. Enzyme activity was present in 27 urine samples and in 27 (82%) bladder washings collected from cancer patients. We did not find correlation between the activity in urine and washings, and their mean levels were not different (22.2 +/- 10.1 and 20.7 +/- 8.0, respectively). Telomerase activity in bladder cancer tissues was correlated to its activity in urine (r = 0.650, P < 0.001) and in bladder washings (r = 0.410, P < 0.05). Only 2 of 20 urine samples from control subjects were found to express telomerase activity at a very low level. This was the first attempt to correlate telomerase activity in exfoliated cells from urine and bladder washings with the activity in corresponding bladder cancers. According to these results we postulate that telomerase activity in urine sediment reflects the activity in bladder cancers better than bladder washings and, for its easy collection, is to be preferred as diagnostic marker in this tumor.

Epithelial Cells↗

Cystometric evaluation of bladder function in non-anesthetized mice with and without bladder outlet obstruction.

PURPOSE: To develop a model for cystometric study of bladder function in the awake mouse, and to characterize urodynamically and immunohistochemically the non-obstructed and infravesically obstructed mouse bladder. MATERIALS AND METHODS: Non-obstructed Balb/CJ mice, and mice with bladder outlet obstruction after surgical, partial ligation of the urethra underwent continuous cystometry as previously described for rats. Bladders were also investigated by immunohistochemistry. RESULTS: During the period of cystometry, reproducible micturition patterns were obtained. Marked differences in the urodynamic parameters between non-obstructed and obstructed mice were revealed. In mice subjected to urethral obstruction, micturition pressure (p <0.05), threshold pressure (p <0.05), bladder capacity (p <0.001), micturition volume (p <0.001), and residual volume (p <0.05) increased significantly. There was no difference in basal pressure or compliance between non-obstructed and obstructed mice. Non-voiding bladder activity was consistently recorded in obstructed mice; both frequency and amplitude increased significantly (p <0.01). Compared with non-obstructed bladders, obstructed bladders showed hypertrophy of the bladder wall and various degrees of "patchy denervation" of the detrusor. When tested in non-obstructed mice capsaicin, prostaglandin E2 (intravesical administration) and apomorphine (subcutaneous administration) induced bladder overactivity. CONCLUSIONS: Continuous cystometry can be reproducibly performed in awake, freely moving non-obstructed mice and mice with bladder outflow obstruction. The changes induced by infravesical obstruction in mice were similar to those previously found in rats. This model may be useful for investigations of genetically modified mice.

Animals↗

Modulation of bladder alpha1-adrenergic receptor subtype expression by bladder outlet obstruction.

PURPOSE: alpha1-Adrenergic receptor (alpha1AR) antagonists are effective for relieving obstructive and irritative symptoms in patients with bladder outlet obstruction. While the alpha1aAR is responsible for prostate smooth muscle relaxation and outlet obstruction relief, to our knowledge the mechanisms underlying the relief of irritative symptoms remain to be determined. Therefore, we investigated mechanisms by which bladder alpha1AR subtypes may be involved in this process. MATERIALS AND METHODS: We studied 42 rats, including 6 unoperated controls, 17 sham operated controls and 19 obstructed animals. Animals were characterized for baseline voiding pattern, followed by surgical intervention or sham surgery to establish obstruction (1.09 mm. restricted opening). After 6 weeks to enable the development of detrusor hypertrophy, voiding behavior was reexamined, the animals were sacrificed and bladder tissue was immediately placed in liquid nitrogen. alpha1AR subtype messenger (m)RNA was quantitated using quantitative competitive reverse transcriptase-polymerase chain reaction and protein expression was determined using radioligand binding with the alpha1AR antagonist [125iodine]2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (saturation analysis for total alpha1AR density and competition analysis with BMY7378 and 5-methylurapidel to determine alpha1AR subtypes). RESULTS: In this model 6-week surgical obstruction produced a 6.3-fold increase in bladder weight versus sham operation (p <0.001), concurrent with increased voiding frequency versus before obstruction (p <0.004). Although bladder alpha1AR density did not increase overall with obstruction, striking changes in alpha1AR subtype expression occurred. In control animals 70% of alpha1AR mRNA was the alpha1a subtype, 5% were alpha1b and 25% were alpha1d, whereas in obstructed animals bladder alpha1AR expression changed to 23% alpha1a, 2% alpha1b and 75% alpha1d. Changes in alpha1AR mRNA expression were of similar magnitude throughout the bladder dome, mid body and base. Parallel changes were also evident at the protein level with 100% alpha1aAR expression in control animals changing to new onset alpha1dAR expression (mean plus or minus standard error of mean 36% +/- 7%) in animals with a 5-fold or greater increase in bladder weight. CONCLUSIONS: Our findings indicate a remarkable increase in bladder alpha1dAR mRNA and protein expression after 6 weeks of obstruction and resultant detrusor hypertrophy. This finding is potentially important since alpha1dARs have 10 to 100-fold higher affinity for the endogenous neurotransmitter norepinephrine than the alpha1a or alpha1bAR subtypes. These findings imply that targeting alpha1d may provide a new therapeutic approach for controlling bladder irritative symptoms and possibly detrusor overactivity associated with bladder outlet obstruction.

Animals↗

[Value of exfoliative cytology of the urinary bladder in occult bladder cancer and in the control of treated cancers].

The exfoliative cytology of the urinary bladder is helpful in the detection of occult bladder carcinoma, which in according to definition is not recognizable without magnification, as well as in the follow-up of treated bladder carcinoma. Within a period of 5 years 23 occult bladder carcinomas were detected by cytological studies alone. The degree of malignancy of the established transitional cell carcinoma varied between G2 and G3. The latent period between the found cytological result and the histological confirmation amounted to 14 months. In our experience the diagnosis of occult bladder carcinoma can be established by exfoliative cytology of the urinary bladder, if invisible parts of tumor with moderate and high degree of malignancy communicate with the mucosa of the bladder. The cytological recognition of malignant cells of urothelium offers valuable support for further therapeutic procedures, if there is no cystoscopic evidence of tumor in the bladder. In addition to clinical diagnosis of bladder cancer exfoliative cytology of the urinary bladder should also be part of the follow-up of treated bladder cancer.

Biopsy↗

Effects of mild bladder outlet obstruction on rabbit bladder structure and function.

Mild bladder outlet obstruction was created in 42 New Zealand white rabbits by placing a 5-mm inner diameter polyethylene tube around the urethra. Periods of obstruction lasted for 1 day (7 rabbits), 3 days (7 rabbits), 1 week (7 rabbits), 2 weeks (6 rabbits), 4 weeks (7 rabbits), 6 weeks (4 rabbits) and 8 weeks (4 rabbits). Whole bladder functional study was performed in control (5 rabbits) and the obstructed bladders. The obstructed bladders increased in weight two-to threefold. There was no significant difference in bladder weight after different periods of obstruction. Electric stimulation showed a diminished response after 3 days of obstruction. Pharmacologic stimulation with 500 microM carbachol revealed a decreased response after obstruction, but intravesical pressure returned to the control level at 6 and 8 weeks of obstruction. However, the bladder weight and the expelling function of the obstructed bladders remained the same as on day 1 of obstruction. Histologic study of control and obstructed bladders revealed that: 1) dense submucosal fibrous tissue developed after 3 days of obstruction, 2) detrusor muscle hypertrophy and hyperplasia were noted with intermuscular collagenous fiber deposition after 2 weeks of obstruction, 3) trabeculation of the bladder wall with hyperplasia of muscular bundles was noted after 2 weeks of obstruction, 4) acute edematous and inflammatory reaction were apparent after 3 days and 1 week of obstruction, but resolved later and 5) degenerative changes of muscular cells were noted at 8 weeks of obstruction. The results show that despite apparent morphologic changes after outlet obstruction, no significant difference was observed in bladder expelling between short-term and long-term infravesical mild outlet obstruction. The bladder contractile apparatus appears to have a compensatory ability after mild outlet obstruction.

Analysis of Variance↗

Animal models of bladder outlet obstruction and molecular insights into the basis for the development of bladder dysfunction.

In humans, chronic bladder outlet obstruction resulting from benign prostatic hypertrophy (BPH) can induce severe and irreversible upper urinary tract changes, especially in the bladder. BPH can be mimicked in rabbits by artificially creating a partial obstruction of the bladder outlet. The structural and functional changes initiated eventually elicit a pathology and symptomology similar to human BPH. The rabbit bladder responds to partial outlet obstruction in three characteristic stages: hypertrophy, compensation and decompensation Basic fibroblast growth factor, epidermal growth factor and transforming growth factor-beta appear to be involved in the hypertrophy phase. During this initial phase normal bladder function is maintained but in the later phases, it is drastically impaired. We propose that the various stages of bladder remodelling subsequent to partial outlet obstruction are essentially driven by reduction in blood flow to the bladder (ischaemia). Initially this ischaemia might stimulate a compensatory response enabling the bladder to deal with the stress outlet obstruction. However, the long-term reduction in blood flow resulting from cyclical filling of the obstructed bladder, ultimately induces the degenerative changes that impede bladder function. These findings have important implications for the development of novel therapies to prevent or reverse bladder dysfunction resulting from BPH.

Animals↗