Morning vs evening dosing with doxazosin in benign prostatic hyperplasia: efficacy and safety.

Three hundred and fifty-three patients with symptomatic benign prostatic hyperplasia were randomized to doxazosin or placebo, with morning or evening dosing, to compare the effect of dosing time on the efficacy and safety of doxazosin treatment. After 24 weeks of treatment, the mean International Prostate Symptom Score had decreased by 6.8 units in the doxazosin group compared with 4.5 units in the placebo group (P=0.003). Improvements in Q(max) of 2.03 ml/s and 0.30 ml/s were seen for the doxazosin and the placebo groups, respectively (P<0.001). No differences in efficacy or safety between the morning- and evening-dosed subgroups were observed. Doxazosin was significantly more effective than placebo at improving symptoms of BPH and urinary flow rates at endpoint, and was well tolerated. The time of dosing did not appear to influence the efficacy or safety of doxazosin, suggesting that there is no need to restrict administration of doxazosin to the evening in BPH patients.

Anatomic limitations of prostatic urethra in using cylindrical stents.

The use of metal stents for the relief of prostate obstruction in the elderly has increased in popularity since 1980. The finding that fine metal wire stents become covered with prostatic epithelium led to the recent use of stents that can be left in place permanently. Because the prostatic urethra does not always conform to the cylindrical shape of these stents, and because the bladder neck/urethral angle is not a right angle and may not be circular in outline, problems may occur with positioning and subsequent inadequate epithelial covering. Three-dimensional imaging of the prostatic urethra using transrectal ultrasound scanning during voiding may give additional help in defining the variety of possible shapes of this area, but more work on the compliance of prostate tissue and the shape of the prostatic urethral lumen is essential in order to improve stent design and reduce the risks and complications of these useful devices.

An increase of neuropeptide Y but not nitric oxide synthase-immunoreactive nerves in the bladder neck from male patients with bladder neck dyssynergia.

PURPOSE: To determine the distribution of neuropeptides in male patients with bladder neck dyssynergia and benign prostatic hyperplasia. MATERIALS AND METHODS: Bladder neck tissue, obtained from male patients with bladder neck dyssynergia (BND) and control patients with benign prostatic hyperplasia (BPH), was studied immunohistochemically for protein gene product 9.5 (a general neuronal marker), vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, substance P, growth associated protein 43 and nitric oxide synthase. RESULTS: In the bladder neck from control patients, the greatest density of nerves contained protein gene product 9.5, followed in decreasing order by neuropeptide Y; vasoactive intestinal polypeptide; calcitonin gene-related peptide; nitric oxide synthase; substance P and serotonin. The neuropeptides were found in the smooth muscle and were also associated with blood vessels. In patients with BND there was a statistically significant increase (P < 0.05) in the density of protein gene product 9.5- and neuropeptide Y-immunoreactive nerves in the smooth muscle and the base of the mucosa but not in blood vessels in the bladder neck, while the density of the other neuropeptides studied, nitric oxide synthase and serotonin did not significantly change from that of control tissue. Growth associated protein 43-immunoreactive nerves were absent from the bladder neck from both groups of patients. CONCLUSION: It is suggested that the increase in density of protein gene product 9.5- and neuropeptide Y-immunoreactive nerves, part of the sympathetic contractile system of the bladder neck, may exacerbate bladder outlet obstruction and thus play a role in the pathogenesis of BND.

A method of measuring fluid balance during transurethral resection of the prostate.

OBJECTIVE: To design a practical system for non-invasively monitoring fluid balance during transurethral resection of the prostate (TURP) and other endoscopic procedures. MATERIALS AND METHODS: Load cell transducers are incorporated into a platform placed under the operating table. Output is passed to a digital weighmeter and then to a portable computer. The raw data is filtered using software written by the authors (CAL) and the output displayed both numerically and graphically on the computer screen. The device was tested under laboratory conditions and then assessed in the clinical setting. RESULTS: The device proved stable in both the laboratory and clinical settings. Examples of the common patterns generated during TURP are presented. The prototype has been used routinely in our practice to warn the surgeon and anaesthetist of fluid overload and has been used to monitor fluid balance in several studies. CONCLUSIONS: This instrument provides a practical method of monitoring total fluid balance during TURP. It can be used with either general or regional anaesthesia and provides information not otherwise available. It provides an early warning of significant changes in total fluid balance, particularly irrigant fluid absorption. Use of this device serves to prevent development of the TUR syndrome, a potentially fatal complication of endoscopic surgery. Our ultimate aim is to produce a refined version that is simple, compact and cheap enough to be used routinely in all urological theatres. The cost of a single episode of intensive care for a patient developing iatrogenic complications from irrigant absorption would offset the cost of such a device.

Precautions and complications in the use of the urolume wallstent.

The Urolume Wallstent was first used to treat urethral strictures in 1987. Its place in the treatment of urethral strictures is now well established and we have used it successfully in over 100 patients. Recent interest in alternative methods of treating benign prostatic hyperplasia (BPH) has led to the use of this and other stents in patients with symptomatic BPH who are a poor surgical risk. Over 270 patients have been treated by us with the Urolume Wallstent with satisfactory results. More recently we have also used this stent as an alternative to transurethral resection of the prostate in fat patients. Although the Urolume Wallstent is easy to use and clinically effective, complications can arise if proper care is not taken during its insertion. As the stent has become more widely used more problems and difficulties have been experienced. We discuss these and describe the precautions which should be taken in the use of this device in order to achieve the best results.

Cardiovascular performance and core temperature during transurethral prostatectomy.

Hemodynamic performance and core temperature were recorded during transurethral prostatectomy in 52 patients who were stratified according to cardiac symptom score and then randomized to undergo standard (31) or isothermic (21) transurethral prostatectomy. During the standard procedure ambient temperature (21C) irrigant was used, while during isothermic prostatectomy warmed irrigant at 38C was used to prevent heat loss from the bladder, and a warming blanket and humidifying filter were used to decrease cutaneous and respiratory heat loss. Core temperature decreased by a mean of 0.8C (95% confidence interval -0.9 to -0.7) during standard transurethral prostatectomy and by 0.27C (-0.4 to -0.15) during the isothermic procedure. The standard prostatectomy group showed a significant hemodynamic response consisting of increased mean arterial pressure (p < 0.0002), increased index of systemic vascular resistance (p < 0.0001), bradycardia (p < 0.02), and decreased Doppler indexes of stroke volume (p < 0.005) and cardiac output (p < 0.001). The isothermic transurethral prostatectomy group was hemodynamically stable. These differences between the groups suggest that rapid central cooling exerted a significant effect on perioperative hemodynamic performance during transurethral prostatectomy.

Three-dimensional imaging of the prostatic urethra--an exciting new tool.

OBJECTIVE: To evaluate the technique of three-dimensional (3-D) ultrasound imaging of the urethra and its application in both research and clinical practice. PATIENTS AND TECHNIQUE: The study involved 23 patients: 10 with benign prostatic hyperplasia, four with urethral strictures, three post-insertion of prostatic stents, one with bladder neck dyssynergia, three post-transurethral resection of the prostate, and two with non-urological conditions. A transrectal ultrasound scan was initially performed to acquire a series of images of the urethra. These images were then reconstructed into a 3-D format. RESULTS: The 3-D image of the urethra could be rotated on screen and viewed from any angle. The image could also be sliced at any plane to reveal the sectional view. CONCLUSION: This new tool represents a major advance in imaging techniques and promises to provide new knowledge in understanding the hydrodynamics of the lower urinary tract. The precise geometry of the 3-D urethra will also help in the design of new stents.

A three month double-blind study of doxazosin as treatment for benign prostatic bladder outlet obstruction.

OBJECTIVE: To evaluate the efficacy and tolerability of doxazosin in the treatment of bladder outflow obstruction resulting from benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: One-hundred and thirty-five patients with symptomatic urodynamically confirmed obstructive BPH were treated for 12 weeks with either doxazosin (67 patients) or placebo (68 patients) after an initial 2 week baseline evaluation. The main outcome measures were urodynamic and symptomatic evaluation for efficacy. Blood pressure and adverse events were monitored. RESULTS: Data were obtained in 122 patients (60 doxazosin, 62 placebo). Doxazosin produced increases in both mean and maximum urinary flow rates of 1.01 ml/s and 3.2 ml/s respectively, compared with 0.21 ml/s and 2.2 ml/s on placebo. The increase in mean flow rate was statistically significant (P = 0.04), while that for maximum flow rate approached significance (P = 0.09). The maximum subtracted voiding pressure was substantially reduced (P = 0.007) and 19 of 53 (36%) patients had an increase in maximum flow rate of 50% or more compared with 9 of 54 (17%) on placebo (P = 0.024). Twelve weeks' therapy with doxazosin resulted in significant improvements (compared with placebo) in: hesitancy (doxazosin 26 of 46, placebo 11 of 43; P = 0.003), impaired urinary stream (doxazosin 31 of 55, placebo 16 of 48; P = 0.019) nocturia (doxazosin 22 of 56, placebo 10 of 54; P = 0.017) and urgency (doxazosin 27 of 45, placebo 16 of 42; P = 0.041). Frequency improved with doxazosin therapy (doxazosin 26 of 59, placebo 15 of 55; P = 0.062). Adverse events, most frequently dizziness and headache, were usually mild and transient and led to a discontinuation of doxazosin therapy in one patient. No clinically significant changes in sexual function or blood pressure were seen. CONCLUSION: Doxazosin was well-tolerated and produced both urodynamic and symptomatic improvement in men with BPH, thereby providing a satisfactory alternative to existing drugs with the additional benefit of once daily dosage.

Renal adenocarcinoma in young adults.

Renal adenocarcinoma is rare in young people. The prognosis of the condition would appear to be better in young people justifying a radical treatment rationale even in cases of advanced disease. This report describes a series of patients under the age of 30 with renal adenocarcinoma and a review of the literature. The possible mechanisms for the apparent improved survival of patients in this age group is discussed.

Comparative study of selective alpha 1-adrenoceptor blockade versus surgery in the treatment of prostatic obstruction.

Alternative treatments for benign prostatic hyperplasia (BPH) are the source of much discussion at present. Pharmacotherapy has been demonstrated to have an increasing role in the management of BPH. This study contrasts the efficacy of the selective alpha antagonist prazosin as compared with placebo and the subsequent improvements seen following surgical treatment. Whilst selective alpha blockade has undoubted therapeutic efficacy the improvement in symptom scores and the objective urodynamic measure of the flow rate are not as marked as those seen following surgery.

The urolume, a permanently implanted prostatic stent for patients at high risk for surgery. Results from 5 collaborative centres.

Ninety-six men considered unfit for prostatic surgery underwent the insertion of a permanently implanted super alloy mesh stent (Urolume) at 5 European centres. Ninety were able to void immediately, 2 required a second stent to enable them to void and 4 voided after a period of suprapubic catheter drainage. Seven patients required the subsequent insertion of a further stent to cover the prostatic urethra completely and in 8 cases the stent was removed. Objective and symptomatic evidence of relief of bladder outflow obstruction was shown throughout the period of study. Severe irritative symptoms were seen in the majority of patients for periods of up to 3 months and resulted in removal of the stent in 3. At 12 months, 15 of 27 patients who underwent cystoscopy had complete epithelialisation of the stent and in 11 cases there was more than 70% epithelialisation. Fourteen patients developed encrustation on exposed parts of the stent during follow-up. This was associated with the development of a urinary infection in 9. The positioning of the stent in subsequent studies has been altered to overcome this problem.

The prostatron transurethral microwave device in the treatment of bladder outflow obstruction due to benign prostatic hyperplasia.

There is currently considerable interest in the development of non-surgical means of managing bladder outflow obstruction due to benign prostatic hyperplasia (BPH). We report the results of a 1-year follow-up of 140 men (mean age 67.2 years) presenting with symptoms of bladder outflow obstruction treated for 1 h in a single session by the Prostatron transurethral thermotherapy system. Symptom scores, using a system modified from Boyarsky, fell from baseline values of 23.7 to 11.6. Maximum urinary flow values increased from a mean of 10.1 to 12.4 ml/s. Although residual urine volumes decreased slightly, this was not statistically significant. A self-administered postal questionnaire returned by 114 patients 1 year after Prostatron treatment, and by 87 patients of similar age who had undergone transurethral resection of the prostate (TURP) in the same institution, revealed that patient satisfaction regarding the outcome of each procedure was higher for TURP than thermotherapy. However, more patients suffered sexual dysfunction after TURP than after microwave treatment. It was concluded that although treatment with the Prostatron device produces subjective and objective improvement in a proportion of patients with BPH, more work needs to be done to improve the overall results and to pre-identify patients who experience little or no benefit from this therapy.

Does residual urine predispose to urinary tract infection?

The relationship between the presence of post-micturition residual urine and urinary tract infection is unclear. We have performed a retrospective analysis of 342 studies on bladder emptying and compared the incidence of bacterial infection and pyuria in patients with residual urinary volumes of more or less than 100 ml. In patients with a residual volume > 100 ml 49/219 studies showed evidence of pyuria and 28/198 studies of patients whose residual urine was less than 100 ml showed evidence of infection. In cases where the residuals were > 100 ml 33/123 had evidence of pyuria and 19/109 infection. There was no significant increase in the rate of infection in patients with large residual urinary volumes, suggesting that there is no definite correlation between post-micturition residues and urinary tract infection.

A 12-week placebo-controlled double-blind study of prazosin in the treatment of prostatic obstruction due to benign prostatic hyperplasia.

A series of 93 normotensive patients with benign prostatic hyperplasia and maximum urinary flow rates < 15 ml/s, treated at 2 hospital centres using an identical protocol, was randomly assigned to receive a 12-week course of treatment with prazosin or placebo in a double-blind parallel group trial. A total of 75 patients completed the study and were suitable for the final analysis. Prazosin was administered orally in doses of 0.5 mg and then 1 mg twice daily for 4 days and 2 mg twice daily for the remainder of the trial. Patients on treatment with prazosin exhibited a significantly increased maximum urinary flow rate as compared with placebo, with a significant reduction in maximum voiding detrusor pressure. Prazosin therapy did not produce a significant effect on either frequency or standard parameters of detrusor instability. A double-blind overall assessment of drug efficacy and tolerance significantly favoured prazosin therapy. A total of 30 patients receiving prazosin and 28 receiving placebo reported varied adverse effects. Eighteen patients were excluded from the final analysis, 10 being withdrawn because of adverse effects, 7 on treatment with prazosin and 3 in the placebo group. In long-term usage oral prazosin was well tolerated and appeared to improve obstructed voiding in patients with benign prostatic hyperplasia.

Haemodynamic evidence for cardiac stress during transurethral prostatectomy.

OBJECTIVE: To compare haemodynamic performance during transurethral prostatectomy and non-endoscopic control procedures similar in duration and surgical trauma. DESIGN: Controlled comparative study. SETTING: London teaching hospital. PATIENTS: 33 men aged 50-85 years in American Society of Anesthesiologists risk groups I and II undergoing transurethral prostatectomy (20), herniorrhaphy (eight), or testicular exploration (five). MAIN OUTCOME MEASURES: Percentage change from baseline in mean arterial pressure, heart rate, Doppler indices of stroke volume and cardiac output, and index of systemic vascular resistance, and change from baseline in core temperature. RESULTS: In the control group mean arterial pressure fell to 11% (95% confidence interval -17% to -5%) below baseline at two minutes into surgery and remained below baseline; there were no other overall changes in haemodynamic variables and the core temperature was stable. During transurethral prostatectomy mean arterial pressure increased by 16% (5% to 27%) at the two minute recording and remained raised throughout. Bradycardia reached -7% (-14% to 1%) by the end of the procedure. Doppler indices of stroke volume fell progressively to 15% (-24% to -6%) below baseline at the end of the procedure, and the index of cardiac output fell to 21% (-32% to -10%) below baseline by the end of the procedure. The index of systemic vascular resistance was increased by 28% (17% to 38%) at two minutes, and by 46.8% (28% to 66%) at the end of the procedure. Core temperature fell by a mean of 0.8 (-1.0 to -0.6) degrees C. Significant differences existed between the two groups in summary measures of mean arterial pressure (p less than 0.05), Doppler indices of stroke volume (p less than 0.005) and cardiac output (p less than 0.005), index of systemic vascular resistance (p less than 0.0005), and core temperature (p less than 0.0001). CONCLUSIONS: Important haemodynamic disturbances were identified during routine apparently uneventful transurethral prostatectomy but not during control procedures. These responses may be related to the rapid central cooling observed during transurethral prostatectomy and require further study.

Stricture disease: radiology of urethral stents.

Self-expanding metal stents are emerging as an effective alternative treatment in the management of urethral obstruction. The radiologic studies of 33 men with anterior urethral strictures (subprostatic, n = 11; bulbar, n = 22) that had recurred despite repeated optical urethrotomy and dilation were reported. In all patients, the stricture was successfully treated with stent insertion. Urethrography performed 1 month later in 19 patients showed an irregular intrastent lumen of varying degrees due to a hyperplastic urothelial reaction confirmed at endoscopy the same day. Available follow-up urethrograms in seven patients at 3 months showed that the hyperplasia was settling, and by 6 months, the intrastent lumen was smooth and of good caliber. Urethrography revealed postoperative structures in 14 patients. Strictures seen at 1 month (n = 6) were due to initial stent misplacement and were treated with the insertion of a second stent. Strictures seen 3 months after insertion (n = 4) occurred within the stent lumen and were considered to be significant at endoscopy in only one patient. Strictures that developed 6-12 months after stent insertion (n = 4) were not within the stent and were considered to represent genuine new strictures.

Haemodynamic evidence for per-operative cardiac stress during transurethral prostatectomy. Preliminary communication.

Haemodynamic changes were measured during routine transurethral prostatectomy (TURP). The heart rate and stroke volume fell progressively over the first 30 min of surgery, resulting in a steady reduction in cardiac output. There was a significant increase in left ventricular afterload from commencement of the procedure. These findings demonstrate that haemodynamic responses, which are not detectable using conventional methods of monitoring, occur during TURP. Increased left ventricular afterload indicates increased myocardial work and oxygen demand which could result in myocardial ischaemia. This may contribute to the increased cardiovascular morbidity and mortality which have been reported to occur after TURP. The possible underlying mechanisms are discussed.