R. S. Kirby

Doxazosin in benign prostatic hyperplasia: Effects on blood pressure and urinary flow in normotensive and hypertensive men

OBJECTIVESnTo assess the effects of doxazosin, a selective alpha 1 adrenoceptor inhibitor, on blood pressure and urinary flow in normotensive and hypertensive (sitting diastolic blood pressure more than 90 mm Hg) men with prostatic hyperplasia (BPH).nnnMETHODSnPatients (n = 232) with bladder outflow obstruction due to BPH, classified as normotensive or hypertensive, were enrolled into two, double-blind, placebo-controlled studies. After a washout period of at least 1 week, patients were randomized to doxazosin or placebo, and treatment was continued for 9 to 12 weeks. In addition to measures of standing and sitting blood pressures, the patients response to treatment was also assessed with regard to urinary flow. Although the protocols differed, they were consistent enough to permit pooling of a number of variables.nnnRESULTSnResults from the two studies demonstrated that doxazosin produced a clinically significant reduction in blood pressure only in hypertensive patients (systolic blood pressure/diastolic blood pressure: baseline 162/99 mm Hg, endpoint 143/89 mm Hg); little or no reduction was evident in normotensive patients (systolic blood pressure/diastolic blood pressure: baseline 139/82 mm Hg, endpoint 134/78 mm Hg). Similar effects in terms of uroflow were seen in hypertensive and normotensive patients. The maximum flow rate in hypertensive patients treated with doxazosin increased from 8.82 to 10.84 mL/s (+ 23%) and in normotensive patients treated with doxazosin from 8.52 to 10.90 mL/s (+ 28%). A greater than 30% improvement in maximum flow rate was achieved in 46 of 97 (47.4%) patients in the doxazosin group and 26 of 98 (26.5%) patients in the placebo group. Treatment with doxazosin was effective and generally well tolerated. The majority of side effects were mild or moderate, only slightly higher in the active treatment group compared with placebo, and similar in hypertensive and normotensive patients.nnnCONCLUSIONSnTreatment with doxazosin is effective and well tolerated in the treatment of BPH. It appears to be a particularly appropriate therapy for men with both BPH and hypertension but can be safely administered to normotensive men without causing significant blood pressure reduction. The beneficial effects on urinary flow are similar, irrespective of blood pressure.

Use of the ASI Titanium Stent in the Management of Bladder Outflow Obstruction Due to Benign Prostatic Hyperplasia

An expandable titanium intraprostatic stent was inserted into 30 patients with infravesical obstruction due to benign prostatic hyperplasia (BPH). All of the men were considered unsuitable for transurethral resection of the prostate as a result of comorbid conditions. In 25 patients effective micturition was reestablished with this technique. In 21 of these men, who have been followed for longer than 1 year, the mean maximum flow rate at 1 year was 10.8 ml. per second and the mean residual urine was 56 ml. Although urinary tract infections occurred subsequent to stent insertion in 10 individuals, these resolved after appropriate antibiotic treatment and no stents have had to be removed for this reason. Followup cystoscopy or examination by electron microscopy of those stents that have been removed has shown partial epithelialization of the stent surface in a proportion of patients, and a minor degree of incrustation occurred in 1 case. We conclude that an expandable intraprostatic titanium stent is an acceptable alternative to transurethral resection of the prostate or long-term catheterization in this particular group of high risk patients.

Repeated pressure-flow studies in the evaluation of bladder outlet obstruction due to benign prostatic enlargement

Test‐retest reliability of repeated voids in pressure‐flow studies and the influence on maximum flow rate (QmaxpQ), detrusor pressure at maximum flow rate (pdetQmax), voided volume, and residual urine were studied. Also the agreement in interpretation of pressure‐flow tracings between investigators and a single blinded central reader acting as a quality control center (QCC) were assessed. In addition, correlations between pdetQmax and patient age, International Prostate Symptom Score (IPSS), free maximum flow rate (Qmax), and prostate volume were calculated. Using suprapubic pressure recording, 216 men with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) were investigated in 11 centers. In each pressure‐flow study, three sequential voids were performed, and quality controlled recordings were analyzed for QmaxpQ and pdetQmax by the QCC. Trans‐ rectal ultrasound was used to measure the prostate volume. Mean QmaxpQ did not change, but pdetQmax decreased significantly in the second and third sequential voids. Using the Abrams‐Griffiths nomogram definition of obstruction, 125 patients (67%) were classified as obstructed from the first void, but only 111 patients (59%) from the third void. The agreement between the investigator assessment and that of a single blinded reader was good. There was no significant correlation between pdetQmax and patient age, IPSS, and Qmax, whereas a modest correlation was found between pdetQmax and prostate volume. In summary, there was no significant change in QmaxpQ, but pdetQmax decreased for the three consecutive voids, which can be explained by a decrease in outlet resistance. The agreement between the investigator and QCC interpretations shows the value of a standardized technique, supporting the feasibility of multicenter urodynamic studies. There is a modest, but statistically significant, correlation between detrusor pressure and prostate size, supporting the hypothesis that prostate size is a contributing factor in symptomatic BPH. Neurourol. Urodynam. 18:17–24, 1999.

IMPROVEMENT OF PRESSURE FLOW PARAMETERS WITH FINASTERIDE IS GREATER IN MEN WITH LARGE PROSTATES

PURPOSEnWe assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques.nnnMATERIALS AND METHODSnA modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996.nnnRESULTSnFinasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant).nnnCONCLUSIONSnFinasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.

Reproducibility of uroflow measurement: Experience during a double-blind, placebo-controlled study of doxazosin in benign prostatic hyperplasia

OBJECTIVESnTo evaluate the interindividual and intraindividual variation of uroflow measurements in men with benign prostatic hyperplasia (BPH).nnnMETHODSnA total of 147 men with clinical evidence of BPH underwent two uroflow measurements at each of two screening visits prior to recruitment into a placebo-controlled study of doxazosin in the treatment of BPH. The maximum and mean flow rates were determined on each occasion. Differences in the mean value of both parameters for the cohort were examined. The intraindividual variability was evaluated using intraclass correlation coefficients and differences in maximum uroflow at each visit were examined.nnnRESULTSnUroflow measurements for the cohort were reproducible and there was no clinically significant difference in maximum and mean flow rate on each occasion. However, the intraclass correlation coefficients for the mean and maximum flow rate varied between 0.70 and 0.82, indicating that intraindividual variation accounted for a substantial component of the total variation in uroflow observed among these patients. For many individuals, test-retest differences were clinically relevant.nnnCONCLUSIONSnFor a group of patients, maximum and mean uroflow measurements are reproducible. However, for an individual, these parameters are subject to clinically significant variation and a single measurement may not be representative. This may be important when considering the need for therapeutic intervention.

Oat cell carcinoma of urinary bladder

Oat cell carcinoma of the urinary bladder is extremely uncommon. There have been 52 reported cases in world literature to date. On light microscopic, histochemical, and ultrastructural grounds, these tumors are similar to oat cell carcinoma of the bronchus and other extrapulmonary oat cell carcinomas. Furthermore, they may be grouped together as a clinical entity characterized by an aggressive clinical course with early and extensive metastases, and partial remission with certain chemotherapeutic agents. We report a case of primary small cell carcinoma of the urinary bladder in a forty-two-year-old man and review previous reports with similar histology. The importance of establishing this diagnosis and the optimum forms of therapy are discussed.

A new technique for assessing the efferent innervation of the human striated urethral sphincter.

A technique is described for recording the electromyographic response of the striated urethral sphincter to transcutaneous magnetic stimulation of the brain and spinal cord. A series of 11 control patients have been studied and 3 examples of patients with neurological disease also are reported. The most reliable response was recorded after facilitated transcranial stimulation of the cerebral cortex, with the mean latency of the electromyographic response in the striated sphincter being 26.4 msec. (standard deviation 2.21). It is concluded that assessment of the latency of the striated urethral sphincter electromyographic response to transcranial magnetic stimulation may be a useful technique in the investigation of patients with disorders of micturition.

Alpha-adrenoceptor inhibitors in the treatment of benign prostatic hyperplasia

Although benign prostatic hypertrophy is the most common cause of urinary tract symptoms in men, the cause is still unclear. Recently it has been suggested that treatment with alpha-adrenoceptor inhibitors may be helpful in this condition. Eighty patients with prostatic obstruction were entered into a double-blind parallel study of prazosin versus placebo. There were 25 withdrawals or exclusions, leaving 55 patients for analysis. Mean maximal flow rates increased significantly more in patients treated with prazosin than in patients treated with placebo (p less than 0.005), but there was no significant reduction in maximal voiding pressure. The mean number of voids, recorded on diary cards, was reduced from an initial 10.0/24 hours by 2.1 in the final week, a significantly greater reduction than in the placebo group (p less than 0.01). However, there were no statistically significant changes in the filling cystometrograms. When patients were classified as responders or nonresponders in terms of bladder filling, urine flow, bladder emptying, weekly average of voids/24 hours, and nocturia, the proportion of patients responding to prazosin was significantly greater in all categories except bladder filling and emptying. It was concluded that prazosin at a dose of 2 mg twice daily is a safe and effective treatment for prostatic obstruction and may be used in patients awaiting surgery and in those who are unfit for operation.

Alpha-adrenoceptor blockers in the treatment of benign prostatic hyperplasia

SummaryAlpha-adrenoceptors have been demonstrated within tissues in benign prostatic hyperplasia. In vitro experiments have shown a reduction in smooth muscle tone within prostate strips after addition of alpha-adrenoceptor blocking agents. A small but significant increase in maximal flow rate and improvement in symptoms have been reported in placebo-controlled trials of alpha-adrenoceptor blocking agents. The long-term efficacy of such agents is not yet known.

Treatment Methods for Early and Advanced Prostate Cancer

This book takes the comprehensive management of prostate cancer as its purview. With the current popularity of multidisciplinary management of prostate cancer, however, I was surprised that no radiation oncologists or medical oncologists were included among the editors. Although a solid effort, this text suffers from its lack of nonsurgical input. This textbook comprises three sections, covering general issues, treatment of localized prostate cancer, and treatment of locally advanced and metastatic prostate cancer. Section 1 includes five chapters and covers mortality trends, patient decision making, and quality-of-life issues, including sexual function. This section is well written and helpful. The section on the treatment of localized prostate cancer presents some issues. This section starts with chapters comparing patients’ quality of life after treatment of localized prostate cancer and natural history and expectant management compared with definitive treatment. Chapters 9–19 cover surgery exhaustively, from classic open approaches to robotically assisted laparoscopy. I found the chapter on lymphadenectomy to be particularly helpful— a ‘‘must read’’ for urologists, especially those doing robotic surgery on patients with intermediate-risk or low-volume, high-risk disease. These chapters are followed by five chapters covering radiotherapy, from external beam to brachytherapy (high dose rate and low dose rate), partial organ irradiation, and treatment of high-risk early-stage disease. There is a chapter on high-frequency ultrasonography, as well as chapters on cryotherapy as primary treatment and as salvage treatment. The chapter on the management of an increasing prostatespecific antigen level after prostatectomy, written by two surgeons, is outdated and sometimes incorrect, and should have been co-authored by a radiation oncologist. The chapter by a urologist on evidence-based comparisons of treatment methods also should have had a radiation