The Effect of Bladder Outlet Obstruction Treatment on Ultrasound-Determined Bladder Wall Thickness

ULTRASONOGRAPHY TO MEASURE BLADDER OUTLET OBSTRUCTION The Effect of Bladder Outlet Obstruction Treatment on Ultrasound-Determined Bladder Wall Thickness Andrea Tubaro, MD, FEBU, Cosimo De Nunzio, MD, Alberto Trucchi, MD, FEBU, Giovanni Palleschi, MD, Lucio Miano, MD Department of Urology, Sant’Andrea Hospital – 2nd School of Medicine, “La Sapienza” University, Rome, Italy 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 a-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. [Rev Urol. 2005;6(suppl 6):S35-S42] © 2005 MedReviews, LLC Key words: Bladder • Benign prostatic enlargement • Bladder wall thickness • Ultrasound-estimated bladder weight • Ultrasonography enign prostatic enlargement is a common condition in elderly men, caused by a histopathologic disease called benign prostatic hyperplasia (BPH), which usually develops after the fourth decade of life and can lead to lower urinary tract symptoms (LUTS). LUTS related to BPH can have a negative impact on quality of life. Various degrees of bother have been reported, causing interference with daily activities and decreased psychological well-being and functional status. Although men with LUTS due to BPH are generally managed with watchful waiting or medical therapy, some of them present a slow but progressive B VOL. 7 SUPPL. 6 2005 REVIEWS IN UROLOGY S35 Effect of BOO Treatment on Bladder Wall Thickness continued disease that can result in symptom deterioration, acute urinary retention, urinary tract infection, renal failure, and the need for surgery.1,2 The progressive nature of this disease has been recently confirmed in studies of the natural history of BPH, evaluating the modification of symptoms over time in population and patient cohorts and in the placebo arms of intervention studies, in because quick its action and thick its coats.”6 The anatomic changes of the obstructed bladder, described at autopsy, constitute the rationale for the endoscopic diagnosis of BOO. Clinical studies have shown that the specificity of such a diagnostic approach is unsatisfactory, notwithstanding its high sensitivity. Evaluation of bladder hypertrophy on light microscopy was disappointing, but Partial outlet obstruction results in a significant increase of bladder weight, neoangiogenesis, and reduction of the blood flow to smooth muscle fibers. which the progression of the disease was assessed according to the occurrence of BPH complications.3 Data from the Medical Therapy of Prostatic Symptoms study suggested that renal failure is a very rare complication of BPH: none of the 2800 patients enrolled in this study experienced significant worsening of serum creatinine levels.3,4 Etiology and Diagnosis The etiology of LUTS is multifactorial. In patients with BPH, bladder outlet obstruction (BOO) is considered to contribute to both signs and symptoms of disease severity because of its effect on detrusor function. The increased outlet resistance is related to an anatomic component, deriving from the elevated bladder neck and the enlarged prostate lobes, and to a dynamic component, depending on the increased smooth muscle tone in the prostate gland and bladder neck.5 The effect of BOO on the detrusor was first described in the 18th century in a seminal book by the Scottish surgeon John Hunter, who wrote that “the disease of the bladder arising from obstruction and its consequence is an increased irritability, by which the bladder admits of little distension, S36 VOL. 7 SUPPL. 6 2005 a number of characteristic patterns were identified with electron microscopy. Myohypertrophy, associated or not with disjunction pattern, was reported to be diagnostic of BOO.7 Animal models of BOO, developed in the rat, guinea pig, rabbit, and mini-pig, were instrumental in understanding the pathophysiology of bladder response to increased outlet resistance. Partial outlet obstruction results in a significant increase of bladder weight, neoangiogenesis, and reduction of the blood flow to smooth muscle fibers after an initial increase. In the rat model, significant reduction of blood flow to smooth muscle fibers is observed 2 weeks after the onset of BOO, and it is associated with a severe reduction of contractile function, with impaired response to both bethanechol and choline acetyltransferase.8 Reduction of detrusor contractility, as measured on isolated bladder strips, is a characteristic feature of bladder decompensation. After an initial compensated phase, during which bladder muscle is stable and 80% of contractile function is maintained, decompensation of the detrusor muscle occurs, with progressive increase of bladder mass and REVIEWS IN UROLOGY reduction in bladder function and compliance. From a metabolic standpoint, smooth muscle fiber dysfunction in the decompensated phase is associated with impaired citrate synthase activity and increased phospholipase A2 activity.8,9 A number of biochemical markers have been investigated to demonstrate the increased metabolic activity associated with the increased protein synthesis required for myohypertrophia and collagenosis. Increased deposition of collagen fibers in the obstructed bladder is a well-known phenomenon, which is considered to play a role in the reduced detrusor compliance observed in obstructed BPH patients and elegantly shown in a study by Ushiki and Murakumo.10 Collagen concentrations in biological tissue depend on the balance between collagen production and degradation and vary as collagen fibers are continuously synthesized and degraded. Nielsen11 investigated the effect of relieving BOO on bladder wall hypertrophy (BWH) in the mini-pig model. A significant decrease of bladder weight was observed when the study animals were relieved of obstruction, although bladder mass remained higher than in controls. The observed reduction in bladder hypertrophy was not dependent on the decrease of smooth muscle fibers but rather on a significant decrease of their volume and on a significant decrease in the total collagen content, particularly type III collagen. Increased urethral resistance is considered to result in a cascade of events leading to increased bladder mass, decreased compliance, and compensated detrusor function, causing hypoxia and ischemia followed by reperfusion injury. The effect of reperfusion injury is twofold. Release of Ca2+ from the sarcoplasmic reticulum and mitochondria leads to the activation of calcium-dependent degradative enzymes, such as calpain and Effect of BOO Treatment on Bladder Wall Thickness phospholipase A2. Generation of oxygen free radicals causes lipid peroxidation. Both events might result in specific damage to neuronal membranes, mitochondria, and sarcoplasmic reticulum. Consequently, metabolic dysfunction of smooth muscle fibers occurs with reduction of detrusor contraction and with bladder decompensation. Such a cascade implies a number of potential strategies for therapeutic intervention, including the use of a-adrenoceptor antagonists, prostate surgery, fibrosis inhibitors, vasodilators, angiogenesis stimulators, calcium channel blockers, antioxidants, free radical scavengers, and membrane-protecting agents. Data from different animal models of BOO suggest that the detrusor is not a passive witness but rather plays an active role in the voiding dysfunction associated with BPH. The initial response of the bladder to increased outlet resistance guarantees complete bladder emptying despite the increased workload, but in the long term the isometric stress of detrusor fibers might lead to bladder decompensation. No consensus has been reached yet as to the definition of bladder decompensation in BPH patients. Detrusor contractility in vivo can be measured with the power factor, although its relationship to in vitro contractile properties of isolated muscle fibers is unknown. At present, no parameter or threshold has been proposed or defined for the diagnosis of bladder decompensation in patients. More importantly, no consensus has been reached as to the “point of no return,” beyond which bladder function will not recover after the removal of outlet obstruction. The relationship between detrusor contractility and complications of A significant decrease of bladder weight was observed when the study animals were relieved of obstruction. BPH, such as high residual urine volume and acute and chronic urinary retention, is unclear. A theoretical cascade of events leading from BOO to urinary tract infection, bladder stones, chronic renal failure, and the need for surgery is shown in Figure 1. Research in this area is eagerly awaited. Urodynamic investigations, particularly pressure–flow studies, are the gold standard for the diagnosis and grading of outflow obstruction Bladder Outlet Obstruction Bladder Wall Hypertrophy Impaired Detrusor Contractility Increased Residual Urine Urinary Tract Infection Bladder Stones Acute Retention Chronic Retention Surgery Chronic Renal Failure Figure 1. Progression of benign prostatic hyperplasia. and detrusor contractility. Invasive urodynamic tests and uroflowmetry are not recommended in primarycare evaluations of patients with LUTS due to BPH, although they remain optional for patients whose symptoms do not match clinical findings, for patients who do not respond to medical treatment, and for those scheduled for minimally invasive treatment or surgery. Treatment of LUTS due to BPH is rarely mandatory, as when chronic renal failure due to urinary retention develops; more often treatment is indicated because of the bothersomeness of LUTS for the patient. Information about the natural history of BOO and bladder hypertrophy is scanty.12,13 The aim of this article is to review the information available in the peer-reviewed literature regarding the effect of treatment of BOO on detrusor hypertrophy. Clinical Assessment of Bladder Hypertrophy Tubaro and Miano14 first proposed the analogy between the effect of an increased workload in the bladder and in the heart in 2002. Notwithstanding the obvious differences between the detrusor and heart muscle fibers, both organs might suffer pressure and volume overload. In the urinary bladder, pressure overload occurs when the enlarging prostate causes increased outlet resistance, leading to an early hypertrophic compensatory response. In some patients the obstructive condition might progress, ultimately leading to decompensation with volume overload caused by chronic retention. In cardiology, VOL. 7 SUPPL. 6 2005 REVIEWS IN UROLOGY S37 Effect of BOO Treatment on Bladder Wall Thickness continued ultrasonography is the standard of care to evaluate the hypertensive damage. In urology, estimation of detrusor mass by suprapubic ultrasound was first proposed in the pediatric population to diagnose the possible hypertrophic response to increased outlet resistance in patients with urethral valves.15 children and in young, thin adults but might be difficult and cumbersome in elderly or obese men or in cases of hairy pubis or suprapubic scars from abdominal surgery. Comparison of mean bladder volumes between in-and-out catheterization and ultrasonography suggests a relatively high overall accuracy, although significant In 1994, Schoor and coworkers suggested the possibility of diagnosing BOO in rabbits by ultrasound measurement of bladder wall thickness. In 1994, Schoor and coworkers16 suggested the possibility of diagnosing BOO in rabbits by ultrasound measurement of bladder wall thickness (BWT). In 1996, Kojima and coworkers,17 formerly at Kyoto University, first proposed the ultrasound estimation of detrusor mass in patients with BPH. Provided the bladder can be assumed to be a sphere, the ultrasound-estimated bladder weight (UEBW) can be calculated by subtracting the intravesical volume (4/3 p 3 iR3) from the total vesical volume (4/3 p 3 tR3), where iR is the intravesical radius and tR the total radius, given by iR 1 BWT. Given a specific weight of 1, bladder weight and mass coincide. The Japanese investigators evaluated 104 patients with LUTS and observed a mean UEBW value of 37.3 g 6 18 g. To test the reproducibility of the technique in relation to bladder filling, measurements were performed with the bladder filled at different volumes (100–300 mL). UEBW values were found to be relatively consistent, with a mean variability of 11.9% 6 6.7%.18,19 Calculation of detrusor mass suffers from 2 possible biases: the estimation of bladder wall thickness and the measurement of bladder volume. Suprapubic estimation of bladder wall thickness is easily performed in S38 VOL. 7 SUPPL. 6 2005 differences can be observed in individual patients. Relatively small differences in the estimation of bladder volumes might result in large variations in detrusor mass. In 1998, Manieri and coworkers20 investigated the relationship between BWH and urodynamic parameters of outlet resistance. To minimize the technical bias due to ultrasound measurement, BWT was measured at standard bladder volume of 150 mL with a 3.5-MHz mechanical sector probe and a suprapubic approach. Intraobserver and interobserver variability were calculated. On suprapubic ultrasound, 2 hyperechoic lines identify the outer and inner surfaces of the detrusor muscle, corresponding to subserosal tissue and to bladder mucosa plus submucosal tissue, respectively. A minimum of 3 measurements was obtained from the anterior or lateral bladder walls and averaged. The mean BWT was 4.5 mm 6 1.1 mm. A 4.6% to 5.1% intraobserver variability and a 12.3% interobserver variability were observed. The investigators acknowledged the disadvantages of this method, which was proposed to minimize measurement bias and to prove the concept that BWH was correlated with detrusor function. The limitations of such an approach in daily practice are self-evident. The high level of correlation found between BWT and urodynamic parameters exceeded expectations and provided a strong rationale for further technical developments that might bring the estimation of BWH into daily urologic practice. Further insight into the technical problems of the measurement of BWT was provided by Oelke and coworkers,21 who evaluated the change of thickness values at various bladder volumes. Generally speaking, at high bladder volumes the change in BWT values might be lower than the ultrasound resolution. According to Oelke, constant BWT values were found between 60% and 100% of bladder capacity, whereas a continuous change of BWT could be measured for the first 50% of bladder capacity. Figure 2. Ultrasound imaging of the bladder wall with the BladderScan® BVM 6500 (Diagnostic Ultrasound, Bothell, WA). REVIEWS IN UROLOGY Effect of BOO Treatment on Bladder Wall Thickness 6.0 BWT (mm) 5.5 5.0 4.5 4.0 3.5 3.0 Unobstructed Equivocal Obstructed Figure 3. Bladder wall thickness (BWT) for the different classes of obstruction, stratified according to the AbramsGriffith nomogram (mean values and 95% confidence intervals). Following the early experience in the evaluation of detrusor mass and BWT, the possibility of automatic identification of the bladder wall on ultrasound by a dedicated computer algorithm was postulated and finally translated into a dedicated instrument: the BladderScan® BVM 6500 (Diagnostic Ultrasound, Bothell, WA).22 The instrument uses state-of-the-art technology for the measurement of bladder volume (24 isocentric scans of the bladder) and a special algorithm for automatic pattern recognition, which identifies the outer and inner borders of the bladder wall (Figure 2). Variability of less than 5% is reported for bladder volumes of 200 to 400 mL. Bladder Mass, Bladder Wall Thickness, and BOO Analysis of BWT in cadavers showed consistent values in different bladder areas. The relation of BWT and bladder mass was found to be almost perfect (r 5 0.97, P < .001).17 These investigators found that consistent UEBW could be obtained at bladder volumes between 100 mL and 300 mL. Comparison of UEBW in control subjects and subjects with normal outlet resistance versus those with BOO revealed a significant difference between the first 2 groups (25.6 g 6 5.7 g and 28.4 g 6 4.2 g, respectively) and obstructed patients (49.7 g 6 19.5 g). Evaluation of BWT values in patients with different values of bladder resistance showed a significant positively correlated with detrusor contractility and outlet obstruction, as measured by the projected isometric pressure (r 5 0.62, P < .0001), opening detrusor pressure (r 5 0.67, P < .0001), detrusor pressure at maximum flow (r 5 0.76, P < .0001), and minimum voiding detrusor pressure (r 5 0.61, P < .0001). As expected, a negative correlation was found between BWT and maximum urinary flow (r 5 20.34, P 5 .0001), whereas a positive correlation was observed between BWT and postvoid residual (r 5 0.33, P 5 .001). Measurement of BWT provided high sensitivity and specificity values for the diagnosis of BOO and matched favorably with maximum flow rate measurement and uroflowmetry (area under the curve of receiver operator characteristic analysis: 0.86 vs 0.69).20 Similar results were reported by Oelke and coworkers,21 who observed a significant difference in BWT values between patients without or with equivocal BOO and those with BOO The possibility of automatic identification of the bladder wall on ultrasound by a dedicated computer algorithm was postulated and finally translated into a dedicated instrument. difference between those with outlet obstruction or equivocal BOO versus unobstructed patients, according to the Abrams-Griffiths (A-G) nomogram. When BWT values were plotted against Schaefer class of obstruction, a stepwise increase of BWT was observed (Figure 3).20 A threshold of 5 mm was identified for the diagnosis of BOO; 89.5% of patients with BWT greater than 5 mm were found to be obstructed according to the A-G nomogram. The relationship between various urodynamic parameters and BWT was investigated, and very high correlation values were observed.20 In general, detrusor hypertrophy was (BWT 5 1.33 mm, 1.62 mm, and 2.4 mm, respectively, P 5 .001). With a BWT cut-off value of 2 mm, sensitivity and specificity values of 63.6% and 97.3%, respectively, were obtained. Kojima and coworkers17-19 found a significant difference in UEBW between patients with BPH and controls (41.1 g 6 19.8 g vs 27.1 g 6 19.8 g, respectively, P 5 .0001) when compared with LUTS patients without BOO. Among patients with LUTS, the diagnosis of BOO was associated with higher UEBW values when compared to LUTS patients without BOO (49.7 g 6 19.5 g vs 28.4 g 6 4.2 g, VOL. 7 SUPPL. 6 2005 REVIEWS IN UROLOGY S39 Effect of BOO Treatment on Bladder Wall Thickness continued urinary flow due to BOO from that related to detrusor underactivity. Table 1 Predictive Values of Detrusor Wall Thickness and UEBW for BOO No. of Patients Ultrasound Probe (MHz) Cut-off Value Positive Predictive Value (%) Negative Predictive Value (%) Manieri et al.20 174 3.5 5 mm BWT 88 63 Oelke et al.21 70 7.5 2 mm BWT 95.5 75 Kojima et al.18 5 7.5 35 g UEBW 87.9 84.4 Study Bladder Mass, Bladder Wall Thickness, and BPH Treatment BWT, bladder wall thickness; UEBW, ultrasound-estimated bladder weight; BOO, bladder outlet obstruction. S40 VOL. 7 SUPPL. 6 2005 possibility of using BWH parameters for the diagnosis of BOO, this was clearly beyond the scope of such exploratory research. The possibility remains that future technologic developments in BWH assessment might provide a diagnostic tool able to confirm or exclude the presence of BOO with a reasonable degree of certainty. In particular, the relationship between BWH and detrusor contractility is of interest because it might fill the gap left by free uroflowmetry, which is unable to distinguish poor 6 Bladder wall thickness (mm) P < .001). A significant correlation between UEBW and various urodynamic parameters was found. UEBW was positively correlated with opening and maximum detrusor pressure (r 5 0.48 and 0.47, P 5 .0001, respectively) as well as with measure of outlet obstruction, such as Schaefer nomogram classes, urethral resistance factor, and A-G number (r 5 0.54, 0.49, and 0.48, respectively, P < .01). Using 35 g as a cut-off value for UEBW, these investigators observed 85.3% sensitivity, 87.1% specificity, and a diagnostic accuracy for BOO of 86.2%. This group also evaluated the relationship between UEBW and detrusor contractility. As expected, UEBW was significantly greater in patients with a normal (41.8 g 6 14.6 g) or stronger detrusor (44.7 6 10.6 g), compared with patients with a weak detrusor (30.3 6 12.5 g, P < .001).17-19 Table 1 shows the positive and negative predictive values of BWT and UEBW for diagnosis of BOO. The high correlation observed between UEBW/BWT and parameters of bladder function as estimated by pressure–flow studies reinforces the concept that morphology, when properly assessed, correlates with function. Although data from the peer-reviewed literature suggest the Treatment of arterial hypertension aims at reducing systolic and diastolic pressure and ultimately reversing ventricular hypertrophy. Treatment of LUTS due to BPH aims at improving patient quality of life by reducing symptom-related bother. Treatment of BOO aims at relieving BPH complications, such as chronic renal failure, hydronephrosis, bladder diverticula, and acute and chronic retention of urine, but also aims at relieving LUTS associated with detrusor dysfunction. The pathophysiology of persisting LUTS after BPH surgery is unknown, although the possible relationship between detrusor dysfunction remaining after BPH surgery and LUTS cannot be excluded. The possibility of using BWH data as criteria for BPH intervention and as outcome criteria for BPH surgery has been proposed. Animal data suggest that BOO relief is associated with significant reduction of BWH, although bladder 5 4 3 2 1 0 Pre 1 wk 6 wk 12 wk 24 wk 52 wk Figure 4. The effect of prostatectomy on bladder wall thickness, measured before (Pre) and at 1, 6, 12, 24, and 52 weeks after surgery. Adapted from Tubaro et al.25 REVIEWS IN UROLOGY Effect of BOO Treatment on Bladder Wall Thickness recovery is never complete.23 The effect of BPH surgery on human detrusor was investigated in two separate studies.24,25 Evaluation of UEBW in patients undergoing prostatic surgery showed a significant decrease, from 52.9 6 22.6 g to 31.6 6 15.8 g at 12 weeks after treatment.24 Interestingly, no change of UEBW was seen in patients with a bladder weight of 80 g or more, suggesting the possibility of irreversible bladder damage in extreme cases of BWH. These data were confirmed by Tubaro and colleagues,25 results on the effect of a-adrenoceptor treatment on BWH were provided by Sironi and coworkers in 200127: the use of an a-adrenergic antagonist in patients with BPH resulted in a significant reduction of UEBW value (from 64.1 g 6 16.2 g to 55.5 g 6 12.7 g, 13% decrease of UEBW) after 6 months of treatment. Tubaro and colleagues28 reported similar results in an Italian multicenter study. In patients with BOO, tamsulosin treatment significantly reduced UEBW (from 45.5 g 6 10.3 g to 38.3 g 6 13.2 g, P < .05, mean Measurement of BWT provided high sensitivity and specificity values for the diagnosis of BOO and matched favorably with maximum flow rate measurement and uroflowmetry. who measured a 44.2% reduction of BWT after open prostatectomy (from 5.2 mm 6 0.7 mm to 2.9 mm 6 0.9 mm) (Figure 4). An interesting insight into the possibility of medical management of BWH was proposed by Das and coworkers26 and others,8,9 who measured a significant increase in blood flow in the urinary bladder in both control and obstructed rats; improvement in the detrusor perfusion was considered to be of importance in reducing BWH. Preliminary difference 7.2 g). No significant change was observed in patients with equivocal BOO (from 39.1 g 6 11.3 g to 34.8 g 6 8.2 g).25 A similar degree of change was found in a European multicenter study, although the change did not prove to be statistically significant owing to problems related to the technique of BWT and bladder volume measurement.29 Conclusion Evaluation of UEBW and BWH after BPH surgery clearly demonstrated a high degree of bladder plasticity and the beneficial effect of relieving BOO. Whether a similar effect can be achieved with medical or minimally invasive treatment is still to be confirmed. The prospect of using BWH and UEBW as clinical parameters to identify the need for BOO treatment and to evaluate its clinical outcome is appealing. Research into this area has been greatly hampered by technical problems in measuring BWH/UEBW with a sufficient degree of accuracy to implement the technique in multicenter trials. The recent development of a dedicated ultrasound system for the automated evaluation of bladder mass is exciting in its implications, although further confirmatory studies are needed to verify the system’s diagnostic accuracy and to test its sensitivity to change. The eventual availability of a valid diagnostic tool might well bring measurement of BWH/UEBW into clinical research on treatments for BPH and possibly into daily ■ urologic practice. References 1. 2. Jacobsen SJ, Jacobson DJ, Girman CJ, et al. Natural history of prosta)tism: risk factors for acute urinary retention. J Urol. 1997;158:481-487. Roehrborn CG, McConnell JD, Saltzman B, et al. Storage (irritative) and voiding (obstructive) symptoms as predictors of benign prostatic Main Points • In patients with benign prostatic hyperplasia, bladder outlet obstruction (BOO) is considered to contribute to both signs and symptoms of disease severity because of its effect on detrusor function. • Estimation of detrusor mass has been proposed to diagnose the possible hypertrophic response to increased outlet resistance. • The high correlation observed between ultrasound-estimated bladder weight/bladder wall thickness (UEBW/BWT) and parameters of bladder function as estimated by pressure–flow studies reinforces the concept that morphology, when properly assessed, correlates with function. • The use of UEBW/BWT as clinical parameters to identify the need for treatment of BOO and to evaluate its clinical outcome is appealing, but research into this area has been greatly hampered by technical problems in measuring UEBW/BWT with a sufficient degree of accuracy. • Automatic identification of the bladder wall on ultrasound by a dedicated computer algorithm has been postulated and translated into a dedicated instrument: the BladderScan® BVM 6500 (Diagnostic Ultrasound, Bothell, WA). 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Reversible change of bladder hypertrophy due to benign prostatic hyperplasia after surgical relief of obstruction. J Urol. 1997;158:89-93. Tubaro A, Carter S, Hind A, et al. A prospective study of the safety and efficacy of suprapubic transvesical prostatectomy in patients with benign prostatic hyperplasia. J Urol. 2001; 166:172-176. Das AK, Leggett RE, Whitbeck C, et al. Effect of doxazosin on rat urinary bladder function after partial outlet obstruction. Neurourol Urodyn. 2002;21:160-166. Sironi D, Levorato CA, Deiana G, et al. Decrease of ultrasound estimated bladder weight during tamsulosin treatment in patients with benign prostatic enlargement. Arch Ital Urol Androl. 2002;74:90-94. Tubaro A, Sironi D, Pizzoccaro M, et al. Effect of tamsulosin on bladder wall hypertrophy in patients with lower urinary tract symptoms suggestive of bladder outlet obstruction [abstract 624]. Eur Urol. 2003; (suppl) 2:158. Tubaro A, Anthonijs G, Avis MW, Snijder R. 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