Pharmacological modulation of ureteric peristalsis in a chronically instrumented conscious pig model: effect of adrenergic and nitrergic modulation.

PURPOSE: To evaluate the role of adrenergic and nitrergic signaling on ureteric peristaltic frequency and contraction force in vivo using a large animal model. METHODS: Twelve female pigs (72 ± 4 kg) were chronically instrumented with an electronic pressure-monitoring catheter in the right ureter. Nephrostomy, cystostomy, and arterial and venous catheters were left in situ. Ureteral peristalsis was recorded before and after the administration of propranolol, isoprenaline, doxazosin, urapidil, phenylephrine, LNNA (Nω-nitro-L-arginine), and L-arginine. RESULTS: α1-Adrenergic receptor stimulation resulted in an increased P max and peristaltic frequency. However, α1-inhibition decreased P max alone. Similarly, ß-adrenergic stimulation decreased P max and peristaltic frequency, whereas ß-inhibition increased only P max. LNNA administration increased P max in the distal ureter and hydrostatic pressure in the pyelocalyceal system. L-Arginine did not affect P max or frequency, but resulted in a significantly higher diuresis. Either agonist or antagonist of NO did not affect peristaltic frequency and length of contraction. CONCLUSIONS: Activation of α- and ß-adrenergic receptors, respectively, stimulates and inhibits ureteric peristalsis. The biological effect of NO on ureteric motility is regionally determined and corresponds to the distribution of NOS-positive nerves. Inhibition of NOS activity increases P max in the distal ureter and tonic activity of the ureteric muscle resulting in higher hydrostatic pressure in the renal pelvis.

Pharmacological modulation of ureteral peristalsis in a chronically instrumented conscious pig model. I: Effect of cholinergic stimulation and inhibition.

PURPOSE: We evaluated in vivo the role of muscarinic receptors on ureteral peristaltic frequency and contraction force in a large animal model using pharmacological manipulation. MATERIALS AND METHODS: A total of 12 female pigs weighing a mean +/- SEM of 72 +/- 4 kg were chronically instrumented using an electronic pressure monitoring catheter in the right ureter. Furthermore, nephrostomy, arterial, venous and cystostomy catheters were placed. Ureteral peristalsis was repeatedly recorded before and after the administration of atropine and carbachol. RESULTS: Systemic and local effects of the 2 agents were observed. Compared with controls we recorded an increase in mean ureteral peristaltic frequency (2.0 +/- 0.3 versus 1.6 +/- 0.6 minutes-1, p <0.05) and mean contraction force (50.1 +/- 1.4 versus 45.3 +/- 1.7 cm H(2)O, p <0.05) during renal pelvis perfusion with 0.25 ml per minute saline. Administration of atropine or carbachol modulated neither the force of contraction nor the frequency of ureteral peristalsis in vivo (p >0.05). CONCLUSIONS: Smooth muscle motor activity at the mid and distal ureter is not modulated by muscarinic receptors. Peristaltic frequency is directly related to the pyelocaliceal load during a rate of diuresis not exceeding animal normal diuresis plus 0.25 ml per minute. Ureteral contraction force increases only in the mid ureter with increased diuresis.

Intraluminal pressure changes in vivo in the middle and distal pig ureter during propagation of a peristaltic wave.

OBJECTIVES: To establish the characteristics of mechanical activity during ureteral peristalsis and unidirectional bolus transport, pressure changes in the middle and distal (juxtavesical and ureterovesical junction) porcine ureter were quantified in vivo. METHODS: Five female New Yorkshire pigs (50 to 60 kg) were studied under halothane anesthesia. The endoscopic approach was used to position an 8-channel 6 F perfusion catheter under direct vision into the distal ureter by way of the orifice. Ureteral activity was studied in two separate sessions at 1-week intervals. The pressure, propagation velocity, and length of the peristaltic waves were analyzed. RESULTS: The average maximal pressure in a not previously instrumented ureter amounted to 35.7 +/- 1.2 cm H(2)O in the mid-ureter, and decreased to 19.4 +/- 1.3 cm H(2)O in the juxtavesical ureter (P < 0.001) and further to 7.2 +/- 1.0 cm H(2)O (P < 0.001) in the submucosal segment. The propagation velocity of the peristaltic wave through the ureter was 2.1 +/- 1.3 cm/s. The length of the pressure peak was 5.9 +/- 1.6 cm. CONCLUSIONS: A ureteral peristaltic contraction wave travels at approximately 2 cm/s and is approximately 6 cm long. It is responsible for the unidirectional transport of a urinary bolus and itself acts as an "active" antireflux mechanism. The maximal pressure in the lumen of the ureter decreased from proximally to distally, but remains sufficiently high at the ureterovesical junction to prevent retrograde urine leakage when the ureter empties its urinary bolus into the bladder and the orifice is open.

Brachytherapy with transperineal (125)Iodine seeds for localized prostate cancer.

BACKGROUND AND PURPOSE: To analyze the treatment results of transperineal (125)Iodine seeds in localized prostate cancer. PATIENTS AND METHODS: Between 1985 and 1996, 102 patients with T1-T2 N0 prostate cancer were treated with transperineal (125)Iodine seed implants at the Academic Medical Centre in Amsterdam. Tumours were classified as T1c in four patients, T2a in 73 patients and T2b in 25 patients. The mean pre-treatment PSA was 17 ng/ml. The (125)Iodine seeds were implanted transperineally under transrectal ultrasound guidance. The mean prostate volume was 31 ml (range 15-48 ml). An average of 49 seeds (range 29-74) was implanted. The dose to the periphery of the prostate was 160 Gy. Until 1988, 27 patients had additional external pelvic irradiation to a dose of 40 Gy in 20 daily fractions of 2 Gy. RESULTS: The 5- and 7-year actuarial survival rates were 77 and 63%, respectively (median 102 months). Ten patients (9.5%) died from prostate cancer. The 5- and 7-year clinical progression rates were 12 and 17%, respectively. Biochemical failure rates at 5 and 7 years were 39 and 44%, respectively. Age, alkaline phosphatase, creatinine, differentiation grade, additional treatment, staging procedure, number of seeds, prostate volume, treatment period and PSA were analyzed as prognostic factors. Only pre-treatment PSA was a prognosticator of clinical and biochemical outcome but not of survival. Biochemical control at 6 years varied from 30% for pre-treatment PSA values higher than 20 ng/ml to 95% for values < or =8 ng/ml. Forty-one out of 49 patients who were sexually active before brachytherapy maintained sexual function during the follow-up. Complete urinary incontinence occurred in one patient. No rectal complications were seen in patients receiving brachytherapy alone. CONCLUSIONS: Transperineal (125)Iodine seeds brachytherapy in localized prostate cancer achieves a good clinical control and overall survival with acceptable late toxicity. Biochemical failure was strongly correlated to the pre-treatment PSA value.

An in vivo endoluminal ultrasonographic study of peristaltic activity in the distal porcine ureter.

PURPOSE: Experiments were performed to quantify the duration and frequency of ureteric peristaltic activity in the laparotomized and non-laparotomized pig in its virgin and postinstrumented states. MATERIALS AND METHODS: Pigs (n = 10) in a steady state of hydration were studied under halothane anesthesia in two groups. The study was undertaken in two separate sessions at a week's interval. In group I laparotomy and vesicotomy were undertaken to obtain ELUS images. In group II, peristalsis was studied using an ELUS probe introduced through the working channel of a 22F rigid cystoscope. Peristalsis was visualized as a periodic diameter-change of ureter and recorded (for approx. 30 minutes) on videotape after an initial period of adaptation of approx. 30 minutes. RESULTS: The ureter acts like a pump discharging urine into the bladder through peristaltic activity. ELUS imaging of ureteric peristalsis correlated well with "eyeballing" of the passage of peristalsis through a ureter (group I). The shortest peristaltic activity in group I was 6.0+/-2.0 seconds in the non-instrumented- and 5.1+/-1.4 seconds in the instrumented ureter. In group II it was 6.8+/-1.5 seconds in the non-instrumented- and 6.4+/-1.5 seconds in the instrumented ureter. Chronic dilatation of ureter led to decrease in peristalsis frequency. Interestingly, acute dilatation caused an increase in ureteric peristalsis frequency. CONCLUSIONS: Ureteric peristalsis acts as a pump discharging urinary boluses (intraluminal fluid load) unidirectionally into the bladder. ELUS provides us an opportunity to quantify and study ureteric peristalsis.

An electro-myographic study of the distal porcine ureter.

PURPOSE: The accumulation of urine in the renal pelvis causes depolarisation of non-specific muscular pace-maker cells. The wave of depolarisation spreads distally in the ureteric smooth muscle cells via gap junctions. This wave of excitation causes a coordinated peristaltic contraction which transports the urine bolus distally to the bladder. The EMG activity in the distal porcine ureter was studied and analyzed to establish the characteristics of ureteric excitation. MATERIALS AND METHODS: Ten female New Yorkshire pigs (50 to 60 kg.) were studied in two groups under light halothane anesthesia (5% at induction and 1% for maintenance anesthesia). In both groups each pig was studied in two separate sessions at a week's interval. In group I (n = 5), bipolar needle electrodes (o: 0. 09 mm.) were implanted through a lower mid-line abdominal incision in the posterior bladder wall, the trigone and the pelvic ureter at intervals of 3 and 8 cm., respectively, from the ureteric orifice. In group II (n = 5), EMG spike burst activity was studied using a twin bipolar ring-electrode attached to an endoluminal ureteric catheter. EMG complexes were recorded using 0 to 30 Hz filters. The duration of spike burst complexes and their intervals were analyzed using a Nicollet, Pathfinder II(R) machine and a Poly(R) 4.9 digital signal processing program. RESULTS: Two types of spike burst activity could be distinguished between the electrodes: A, the migrating type and B, the non-migrating type. Frequency distribution analysis of spike burst duration revealed two main classes in experimental group II, a short spike burst (96%) which lasted 4.5 +/- 1.8 seconds and a longer one lasting 13.4 +/- 1.5 seconds. The conduction velocity of the migrating spike bursts (n = 177, 42% of total) between the proximal and the distal electrode had an average of 2.3 +/- 1.3 cm./sec. No relationship was found between the duration of the proximal spike burst and the conduction velocity. Data from experimental group I correlated well with data from group II. CONCLUSIONS: The results of our EMG study in the distal ureter reveal an approximately 9 cm. long electrically active zone in >/= 90% of EMG activity recordings. The duration of activity was approximately 5 seconds. Such an excited segment of ureter led to a contraction which occluded the ureter and could prevent retrograde leakage of intraluminal contents.

A study of ureteric peristalsis using a single catheter to record EMG, impedance, and pressure changes.

Ureteric peristalsis transports a urinary bolus from the renal pelvis to the bladder. We developed an intraluminal catheter with a pressure transducer on it to study intraluminal pressure changes and a twin bipolar electrode to record the ureteric EMG and impedance (Z) changes during a peristaltic wave. Five female New Yorkshire pigs (50-60 kg) were studied under light halothane anesthesia (5% at induction/1% for maintenance). A steady state of hydration was maintained using intravenous saline infusion. EMG spike burst activity was studied at a 10-cm interval using low (0-30) Hz filters. Impedance between the same electrodes is measured simultaneously in higher frequencies (1-5 KHz) as a function of ureteric motor activity. Pressure generation in the ureteric lumen was also measured simultaneously by a transducer on the same catheter. A digital signal processing program (Poly 4.9) was used for analysis. Parenteral furosemide was used to induce diuresis. Resting ureteric impedance (Z(R)) decreases to Z(B) (Z bolus) during the passage of the urinary bolus. Passage of a contractile zone during a peristaltic wave increases impedance from Z(B) to its Z(R) level and initiates a pressure rise. Bolus length (the length Z(B)) is not constant and decreases distally. EMG corresponds well in time to impedance. Z(R) disappears after infusion of furosemide because of increased urine load and changes of intraluminal ionic environment. The contractile segment of a ureteric peristaltic wave appears to be represented by an elevated Z segment (Z(C)). Pressure rise is recorded only at the beginning of a contractile zone. A specially adapted intraluminal catheter can be used to study peristalsis in the upper urinary tract. One can study all the three components of ureteric peristalsis (excitation, contraction, and intraluminal pressure rise) using such a catheter.

Anatomy of ureterovesical junction and distal ureter studied by endoluminal ultrasonography in vitro.

PURPOSE: The emerging technique of endoluminal ultrasonography (ELUS) provides a new modality for endoscopic visualization of the urinary tract which needs to be further evaluated. We studied the normal anatomy of distal ureter and ureterovesical junction using ELUS. MATERIALS AND METHODS: An assessment of in vitro ELUS ureteric images undertaken at 1 mm. intervals from 8 fresh human cadaver pelvis blocs of bladder and distal ureter were compared with findings of serial histological sections of the same specimens (stained for cholinesterase isoenzymes) to assess the degree of correlation. Computer-assisted 3D reconstructions were made. RESULTS: The different components (ureteric, detrusor and periureteric tissue) of the UVJ could be identified on the basis of echogenicity and form, but differentiation between the respective muscle layers in the wall of the ureter or of the detrusor was not possible. Nevertheless, ureteric volume measurements and an assessment of transmural ureteric length and the angle of passage through the bladder wall were possible. CONCLUSIONS: ELUS is able to differentiate between the ureteric and detrusor muscle and the UVJ gross anatomy can be reconstructed. ELUS technology, however, fails to differentiate between individual muscular layers of the ureter or the detrusor. Further improvement in ELUS is mandatory.

The ICS-'BPH' Study: uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction.

OBJECTIVE: To explore the relationship between uroflow variables and lower urinary tract symptoms (LUTS): to define performance statistics (sensitivity, specificity, positive and negative predictive values) for maximum urinary flow rate (Qmax) with respect to bladder outlet obstruction (BOO) at various threshold values; and to investigate the diagnostic value of low-volume voids. PATIENTS AND METHODS: The study comprised 1271 men aged between 45 and 88 years recruited from 12 centres in Europe, Australia, Canada, Taiwan and Japan over a 2-year period. Symptom questionnaires, voiding diaries, uroflowmetry and pressure-flow data were recorded. The relationship between uroflow variables and symptoms, Qmax and BOO, and the diagnostic performance of low volume voids were analysed. RESULTS: The relationship between symptoms and uroflow variables was poor. The mean difference between home-recorded and clinic-recorded voided volumes was -48 mL. Qmax was significantly lower in those with BOO (9.7 mL/s for void 1) than in those with no obstruction (12.6mL/s; P<0.001) and Qmax was negatively correlated with obstruction grade (Spearman's correlation coefficient -0.3, P<0.001), even when controlling for the negative correlation between age and Qmax (Spearman's partial correlation coefficient -0.29, P<0.001). A threshold value of Qmax of 10 mL/s had a specificity of 70%, a positive predictive value (PPV) of 70% and a sensitivity of 47% for BOO. The specificity using a threshold Qmax of 15 mL/s was 38%, the PPV 67% and the sensitivity 82%. Those voiding <150 mL (n=225) had a 72% chance of BOO (overall prevalence of BOO 60%). In those voiding >150 mL the likelihood of BOO was 56%. The addition of a specific threshold of 10 mL/s to these higher volume voiders improved the PPV for BOO to 69%. CONCLUSION: While uroflowmetry cannot replace pressure-flow studies in the diagnosis of BOO. it can provide a valuable improvement over symptoms alone in the diagnosis of the cause of lower urinary tract dysfunction in men presenting with LUTS. This study provides performance statistics for Qmax with respect to BOO: such statistics may be used to define more accurately the presence or absence of BOO in men presenting with LUTS, so avoiding the need for formal pressure-flow studies in everyday clinical practice, while improving the likelihood of a successful outcome from prostatectomy. This study also shows that low-volume uroflowmetry can provide useful diagnostic information and that, as such, the data from such voids should not be discarded.

Sexual dysfunction in men with lower urinary tract symptoms.

The conventional view that sexual function is not adversely affected by lower urinary tract symptoms (LUTS), assumed to be caused by enlargement secondary to benign prostatic hyperplasia (BPH), was investigated in this study of 423 men aged 40 years and over in a community population in the UK and 1271 urology clinic attenders aged 45 years and over in 12 countries, using the ICSmale and ICSsex questionnaires. Sexual dysfunction was found to be common: in the community, age standardized prevalences of reduced rigidity of erections were 53%, reduced ejaculation 47%, and pain on ejaculation 5%; in clinic men, age standardized prevalences of reduced rigidity of erections were 60%, reduced ejaculation 62%, and pain on ejaculation 17%. Sex lives were reported to be spoiled by LUTS in 8% of community men and 46% in the clinic. There were negative trends for age in the extent to which clinic men were bothered by these symptoms, although older men were still very concerned. Significantly raised odds ratios of sexual dysfunction were found in those with LUTS, especially storage symptoms associated with incontinence. Urinary flow rates were not associated with sexual symptoms. Sexual dysfunction is, therefore, strongly associated with LUTS, is a matter of concern to the men affected, and should be taken into account when managing patients with LUTS.

Multichannel urethral pressure profiles: reproducibility and three-dimensional representation.

Urethral pressure profilometry (UPP) is used to investigate the pressure distribution in the urethra. Single UPP is dependent on the orientation of the catheter during the study. To circumvent this problem, we developed a system for multichannel profilometry (MCUPP) that can be used in daily clinical practice. In the study reported in this article, 29 healthy female volunteers (mean age 34.6 years) underwent MCUPP. The mean time needed to make five pressure profiles ranged from 4 to 12 minutes (mean 7.6). The system is patient- and user-friendly. The volunteers scored the discomfort on a 1 to 10 scale, with 10 meaning no discomfort at all, rendering a mean score of 7.6. The Symmetry Index (SI) is a calculated variable expressing the asymmetry in the pressure profiles. An SI of 1 means a completely symmetrical pattern of pressure distribution. The mean SI for the whole group was 0.7 (range 0.407-0.930). The standard deviation was 0.109. Within-subject SI was highly reproducible (Greenhouse-Geisser epsilon = 0.98292).

Technical features of the system used to perform multichannel urethral pressure profilometry.

Multichannel Urethral Pressure Profilometry (MCUPP) is a method used to get more information on the pressure distribution within the female urethra. This information may be of value in the diagnostic work up of women with urinary incontinence. Different systems are used for this technique. The pump is an important part of such a system. The catheter is perfused with water pumped through the side hole of the catheter. Air bubbles inside one or more of the eight channels alter the elastic properties of the catheter making the results unreliable. In daily urodynamic practice it is important that the system is patient and user-friendly, is quick to set up, and the performance of measurements is easy. For this reason a new type of pump was developed that is able to produce a pressure stable continuous flow through the eight channels of the catheter. The problem of air bubbles has been solved and different measurements can be performed serially in a short time. The system currently used by us is described.

Endoluminal ultrasound of the urethra: a new modality for cross-sectional imaging of the urethra?

Endoluminal ultrasound (ELUS) with high-frequency transducers is a new technique for imaging tubular structures. In combination with a rotating mirror, 360 degrees cross-sectional images of the wall can be obtained. Because of the high frequency, the axial resolution is much higher and thus more detail can be seen. In the study reported in this article, ELUS was performed to image the wall of the female pig urethra to see whether cross-sectional images obtained by ELUS could be correlated with anatomic cross sections of the urethra. Commercially available transducers with a frequency of 30 and 20 MHz were used, the latter having the best suitable frequency for this procedure. The images were of high quality and the different anatomic layers could be clearly visualized. The mucosa/submucosa, the external sphincter, and the surrounding serosa were all identifiable. The correct interpretation was also confirmed by histological cross-section study. We believe that endoluminal ultrasound is a very promising technique for imaging the urethra. Further studies need to be conducted to improve the catheters for urological use and to develop the clinical usefulness of this technique.

Functional anatomy of the human ureterovesical junction.

BACKGROUND: The valve function of the ureterovesical-junction (UVJ) is responsible for protection of the low pressure upper urinary tract from the refluxing of urine from the bladder. Controversy about the microanatomy of the human ureterovesical-junction persists. METHODS: Ten (3 male and 7 female) fresh cadaveric bladders (mean age 70 years old) were studied. The bladders were fixed within 24 hours postmortem, frozen, and serially sectioned. Acetyl- and butyryl- (nonspecific) cholinesterase activity were visualised as described by Karnovsky and Roots. The three-dimensional distribution of the different muscle groups participating in the formation of the UVJ was reconstructed. RESULTS: Three different muscle groups were identified: (1) the detrusor muscle and the deep trigone were mainly acetylcholinesterase-positive, (2) the inner and outer layer of the ureteric muscle were butyrylcholinesterase-positive and merged into a single longitudinal layer at the level of the UVJ and form the superficial trigone distally to the ureteric orifices, and (3) the muscularis mucosae is a discontinuous butyrylcholinesterase-positive layer in the bladder that is absent from the trigone. No evidence of any muscular connection was found between the ureter and bladder musculature. CONCLUSIONS: The anatomy of the UVJ as observed by us suggests the following model of the ureteric peristalsis. The urine bolus arrives in the ureteric lumen at the UVJ level. The ureter can only shorten its length, slides freely in its tunnel, and discharges the urine bolus in the bladder cavity. Ureteric constriction due to the peristalsis and thickening of the contracted portion of the ureter prevents the upstream leakage. Distal spreading of the ureteric "peristalsis" in the superficial trigone increases the submucosal ureteric length and prevents reflux.

The functional anatomy of the ureterovesical junction.

OBJECTIVE: To obtain a new insight into the anti-reflux mechanism of the ureterovesical junction by studying the topographical anatomy of the juxta- and intravesical ureter and its relationship to the surrounding bladder musculature. MATERIALS AND METHODS: Fresh pig bladders were fixed, frozen and serially sectioned. Enzyme histochemistry was performed to demonstrate tissue acetyl- and butyryl- (non-specific) cholinesterase. Smooth muscle cells were identified by immunohistochemistry using a monoclonal anti-alpha actin smooth muscle antibody. Three-dimensional computer reconstructions of the different muscle groups of the bladder and ureterovesical junction were generated. RESULTS: On the basis of expression patterns of the cholinesterase isozymes, five different groups of muscles were identified: the detrusor, the muscularis mucosae of the bladder, the muscle layer of the intravesical ureter and the separate inner and outer muscular layers of the pelvic ureter. CONCLUSION: No separate ureteric sheath was identified. There appeared to be few or no (muscular) connections between the ureter and the bladder musculature. The muscle layer of the ureter ended beneath the mucosa of the bladder, without extension into the trigone. The submucosal section of the ureter was very short, although its length was thought to be of importance in the anti-reflux mechanism. Examination using enzyme histochemistry demonstrated a muscularis mucosae in the bladder which was absent from the trigone.

Ten years survival after recurrent intracranial metastases from a renal cell carcinoma.

The clinical behaviour of renal cell carcinoma is often unpredictable. We report a patient who underwent three palliative resections over 10 years for recurrent intracerebral metastases from a renal cell carcinoma.

Analysis of biopsy findings and implant quality following ultrasonically-guided 125I implantation for localised prostatic carcinoma.

Transperineal ultrasound-guided 125I implantation was undertaken in 52 patients with localised prostate cancer. After implantation, ultrasound-guided biopsies were taken from the previous malignant areas every 6 months in all patients. The percentage of negative biopsies increased from 22% at 6 months to 50% at 48 months. Implant quality was analysed in 37 patients. The difference between isodose levels encompassing the prostate and the aimed levels of 160 Gy was taken as a measure of implant quality. A good quality implant (< 10% underdosage) was found in 43% of patients, a moderate quality (10-25% underdosage) in 35%, and a poor quality implant (> 25% underdosage) in 22%. A statistically significant correlation was found between the quality of the implant and resulting negative biopsy at the original tumour site. Determination of prostate specific antigen (PSA) was not possible from the beginning of the study but an analysis with biopsy findings, implant quality and prostate volume reduction during follow-up has been performed since 1989. A significant correlation was observed between implant quality and serum PSA, and also between volume reduction and serum PSA.

A view on the anatomy of the ureterovesical junction.

Macro- and microscopic dissection of 8 adult and 2 fetal human bladders was undertaken in two directions as part of a study to evaluate ureterovesical junction function. In the trigonal region the detrusor muscle consists of 3, more or less triangular layers. Both ureters are only loosely enveloped by a fibromuscular sheath of mainly bladder origin. This design allows for easy movement of the ureters on their oblique course through the bladder wall. The ureteral muscle fibers play only a minor part in the sheath or join the detrusor muscle. The majority fan out to end at the bladder mucosa or intermingle with fibers originating from the opposite ureter. Since an intricate muscular structure can be demonstrated, an active anti-reflux muscular component in the normal human bladder seems plausible. A classic ureteral sphincter mechanism does not exist. Our findings are discussed and compared with data from the literature.