Comparison of tamsulosin with alfuzosin in the treatment of patients with lower urinary tract symptoms suggestive of bladder outlet obstruction (symptomatic benign prostatic hyperplasia). The European Tamsulosin Study Group.

OBJECTIVE: To compare the efficacy and tolerability of the alpha 1 A-subtype selective drug tamsulosin with the nonsubtype-selective agent alfuzosin in the treatment of patients with lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction (BOO), often termed symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study comprised 256 patients with benign prostatic enlargement and LUTS suggestive of BOO (symptomatic BPH) who received tamsulosin 0.4 mg once daily or alfuzosin 2.5 mg three times daily during 12 weeks of treatment. The response was assessed by measurements of maximum urinary flow rate (Qmax), a symptom score (Boyarsky) and blood pressure at regular intervals. RESULTS: Tamsulosin and alfuzosin produced comparable improvements in Qmax and total Boyarsky symptom score. Both treatments were well tolerated with respect to adverse events. Tamsulosin had no statistically significant effect on blood pressure compared with baseline but alfuzosin induced a significant reduction in both standing and supine blood pressure, compared with baseline (P < 0.05). CONCLUSION: Tamsulosin is the first adrenoceptor antagonist that is selective for the alpha 1 A-subtype; this specificity may explain its lack of effect on blood pressure compared with alfuzosin, an agent that is not receptor subtype specific. Moreover, this finding may partly explain why tamsulosin, in contrast to other currently available alpha 1-adrenoceptor antagonists, can be administered without dose titration. Another advantage compared with alfuzosin (and prazosin) is the once-daily dosing regimen of tamsulosin.

Treatment of high-grade, high-stage prostate cancer with estramustine phosphate or diethylstilbestrol. A double-blind study. The SPCG-1 Study Group. Scandinavian Prostate Cancer Group.

Between 1984 and 1989, 197 patients with T1-4, NX, M1, G2-3 or G3 prostate cancer were randomized to treatment with 560 mg estramustine phosphate (EMP, Estracyt, Emcyt) or 3 mg diethylstilbestrol (DES) per day in a double blind study with stratification on presence or absence of cancer pain at start. A total of 194 patients were evaluated for efficacy of therapy. Time to progression (p = 0.054), to treatment failure (p = 0.036), cancer-specific survival (p = 0.068) as well as overall survival (p = 0.021) were longer in the DES group. There were more patients with prognostic parameters indicating bad prognosis in the EMP group. This trial was designed to study whether EMP had better effect than DES as the primary treatment of high-grade, disseminated prostate cancer. The results did not confirm this hypothesis. On the contrary, treatment with DES had relatively good effect on this very aggressive form of prostate cancer.

Is routine ipsilateral adrenalectomy during radical nephrectomy harmful for the patient?

To investigate the effects of unilateral adrenalectomy on the postoperative course and laboratory parameters, 40 patients with a renal tumour were randomized either to undergo (n = 20) or not to undergo (n = 20) ipsilateral adrenalectomy. Adrenal hormone (cortisol, epinephrine, norepinephrine and aldosterone), adrenocorticotropic hormone, electrolyte, creatinine, growth hormone, glucose, insulin and free fatty acid concentrations were measured preoperatively and postoperatively. Cortisol and epinephrine concentrations were elevated immediately after the operation but returned to preoperative levels within the first 2 postoperative days. There were no significant differences between the adrenalectomy and non-adrenalectomy groups, except that the cortisol concentration was higher in the latter in the afternoon of the day of surgery. The conclusion is that no long-term shortage of adrenal hormones is caused by unilateral adrenalectomy. Other metabolic and endocrine responses were identical in the groups. Thus ipsilateral adrenalectomy does not seem to be harmful to the patient and the need for it must be resolved on the basis of local tumour factors.

[Treatment of benign prostatic hyperplasia with Proscar (finasteride). Results of a 10-year Scandinavian study]. / Behandling av benign prostatahyperplasi med Proscar (finasterid). Resultater av en toårig skandinavisk undersøkelse.

707 patients with moderate prostatic hyperplasia were recruited to a two-year Scandinavian multicenter study. The study was randomized, prospective and double-blind. Half of the patients were treated with finasteride (5 mg daily) and the controls were given placebo. The patients were monitored with regard to symptoms, urinary flow rate and prostate volume. In addition, various laboratory examinations were performed. A statistically significant difference was found between the groups with regard to symptom improvement and increase in urinary flow rate in favour of finasteride. Finasteride reduced prostate volume and stopped further growth, leading to a difference of 30% in prostate volume between the two groups after two years of treatment. Thus, finasteride was able to stop the continuous growth of the prostate in the elderly male. The proportion of patients with adverse clinical experiences was similar in both treatment groups. However, the finasteride-treated group contained more patients with sexual dysfunction. We conclude that finasteride is an alternative to vigilant waiting for patients with moderate symptoms of benign prostatic hyperplasia.

[Finanseride in symtomatic benign prostatic hyeprtrophy. A 2-year placebo-controlled study]. / Finasterid ved symptomgivende benign prostatahypertrofi. Et toårs placebokontrolleret studie. Skandinaviske BPH-Studiegruppe.

The efficacy and safety of treatment with finasteride 5 mg daily for 24 months was assessed in this multicentre double blind placebo-controlled study including 707 patients with moderately symptomatic benign prostatic hyperplasia. Efficacy parameters were changes in voiding- and bladder storage symptoms assessed by a validated symptom score, changes in maximum urinary flow rate and changes in the prostate volume. In the finasteride patients, symptom score improved during the whole study with a significant difference between active treatment and placebo after 24 months (p < 0.01). Maximum flow rate increased in finasteride treated patients resulting in a difference between these and the placebo treated patients of 1.8 ml/s after 24 months (p < 0.01). Prostate volume was reduced by 19% in the finasteride treated patients versus an increase of 12% in the placebo treated patient group (p < 0.01). Finasteride was well tolerated. Patients receiving placebo progressed in symptoms after 16 months. Finasteride can halt the natural progression of moderately symptomatic BPH over a 24 month period.

[Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study.].

OBJECTIVE: To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia (BPH) is maintained over two years, and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months. METHODS: This was a multicenter, double-blind, placeba-controlled study involving 707 patients with moderate symptoms of BPH enrolled at 59 centers in five Scandinavian countries. Following enrollment and a four-week single-blind placebo run-in period, patients were randomized to receive finasteride 5 mg once daily or placebo for 24 months. Urinary symptoms, urinary flow rate, prostate volume, postvoiding residual urinary volume, and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24. Interim physical and laboratory examinations were performed when indicated clinically. RESULTS: In finasteride-treated patients the total symptom score improved throughout the study, with a significant difference between the two groups at 24 months (p<0.01) whereas in placebo-treated patients, there was an initial improvement in the symptom score but no change from baseline at 24 months. The maximum urinary flow rate decreased in the placebo group, but improved in the finasteride group, resulting in a between-group difference of 1.8 mL/s at 24 months (p<0.01). The mean change in prostate volume was +12% in the placebo group versus -19% in the finasteride-treated group (p%lt;0.01). Finasteride was generally well tolerated throughout the two-year study period. CONCLUSIONS: The efficacy of therapy with finasteride 5 mg in improving both symptoms and maximum urinary flow rate and reducing prostate volume has been shown to be maintained during 24 months while patients receiving placebo experienced a return to baseline or deterioration of these parameters during the study. These results demonstrate that finasteride can reverse the natural progression of BPH.

Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. The Scandinavian BPH Study Group.

OBJECTIVES: To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia (BPH) is maintained over 2 years, and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months. METHODS: This was a multicenter, double-blind, placebo-controlled study involving 707 patients with moderate symptoms of BPH enrolled at 59 centers in five Scandinavian countries. Following enrollment and a 4-week single-blind placebo run-in period, patients were randomized to receive finasteride 5 mg once daily or placebo for 24 months. Urinary symptoms, urinary flow rate, prostate volume, postvoiding residual urinary volume, and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24. Interim physical and laboratory examinations were performed when indicated clinically. RESULTS: In finasteride-treated patients the total symptom score improved throughout the study, with a significant difference between the two groups at 24 months (P < or = 0.01), whereas in placebo-treated patients, there was an initial improvement in the symptom score but no change from baseline at 24 months. The maximum urinary flow rate decreased in the placebo group, but improved in the finasteride group, resulting in a between-group difference of 1.8 mL/s at 24 months (P < or = 0.01). The mean change in prostate volume was +12% in the placebo group versus -19% in the finasteride-treated group (P < 0.01). Finasteride was generally well tolerated throughout the 2-year study period. CONCLUSIONS: The efficacy of therapy with finasteride 5 mg in improving both symptoms and maximum urinary flow rate and reducing prostate volume has been shown to be maintained during 24 months while patients receiving placebo experienced a return to baseline or deterioration of these parameters during the study. These results demonstrate that finasteride can reverse the natural progression of BPH.

Long-term effects of finasteride on invasive urodynamics and symptoms in the treatment of patients with bladder outflow obstruction due to benign prostatic hyperplasia.

PURPOSE: We assess the long-term effects of finasteride on bladder outlet obstruction and symptoms in the treatment of patients with benign prostatic hyperplasia. MATERIALS AND METHODS: Of the original 36 patients assigned to treatment with 5 mg. finasteride daily (group 1) or placebo (group 2) for 6 months 27 completed an open extension study of 5 mg. finasteride for 4 more years. The possible relief of bladder outlet obstruction was monitored with repeated pressure-flow studies at baseline, 6 months and 4.5 years. RESULTS: The treatment resulted in a further slight decrease in detrusor pressure at maximum flow rate in group 1 and a significant decrease in group 2 during the 4-year period, whereas improvement in maximum flow rate did not achieve statistical significance. Concomitantly, there was a significant improvement in obstructive and irritative symptoms. CONCLUSIONS: Finasteride decreases bladder outlet obstruction moderately and only occasionally relieves it completely. However, the decrease in obstruction achieved in many patients is sufficient to improve the symptoms significantly. The beneficial effect is long-lasting.

Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer.

Although osteosclerotic bone metastases are characteristic of prostate cancer, mixed metastases with a lytic component are not uncommon. Type I collagen is synthesised by osteoblasts and accounts for about 90% of the organic matrix of bone. We have used new specific immunoassays for PICP (carboxy-terminal propeptide of type I procollagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen) which allow simultaneous assessment of the synthesis and degradation of type I collagen respectively. Forty patients with bone metastases due to prostate cancer at the time of diagnosis were investigated with these methods. Twenty-three of them had sclerotic (S) and 17 had mixed metastases with sclerotic and lytic components (S + L) as assessed by radiographs. The concentrations of PICP and ICTP in serum as well as the activity of alkaline phosphatase (AP) were increased in all patients of the S + L group, who had more aggressive bone disease and a shorter survival than the S group (P < 0.017). The ICTP level was above the reference range in half of the patients in the S group, whereas the PICP and AP levels were elevated in 35%. Of the bone markers, only ICTP was of prognostic significance (P < .05). We conclude that ICTP and PICP give information about the type and activity of the skeletal metastases. In addition, ICTP predicts prognosis.

Comparison of a long-acting LHRH agonist and polyoestradiol phosphate in the treatment of advanced prostatic carcinoma. An open prospective, randomized multicentre study.

In a prospective, randomized open study, a long-acting LHRH agonist (Zoladex) was compared with polyoestradiol phosphate (Estradurin), both widely used in Finland for palliative treatment of prostatic carcinoma, as regards efficacy and side effects. Of the 236 enrolled patients, 129 were randomized to receive LHRH agonist and 107 to oestrogen treatment. The median follow-up was 25 months. Reduction of prostatic volume was quicker and more effective in the LHRH than in the oestrogen group, and serum testosterone concentrations fell to castration level after 1 month and 1 year, respectively. In locally advanced (M0) and histologically well or moderately differentiated tumours, LHRH agonist therapy was considerably more effective than oestrogen as regards time to progression of the carcinoma, but in metastatic (M1) and histologically poorly differentiated tumours both methods gave similar results. Cardiovascular complications showed equal incidence in both groups. LHRH agonist therapy thus seemed to be more effective than polyoestradiol phosphate against locally advanced prostatic cancer in the doses used.

Tumor markers. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

This chapter mainly deals with biochemical aspects on prostate specific antigen (PSA) and its clinical value. To a limited extent, also other tumor markers, which might be of importance in the evaluation of patients with prostate cancer are discussed. In serum, PSA exists in a free form or bound to antichymotrypsin. Interestingly, only 10% of PSA secreted from cancer cells seems to exist in a free form, as compared to 30% of PSA secreted from cells in benign prostatic hyperplasia (BPH). PSA seems to be closely, but not absolutely, related to tumor grade and stage. The mean value of PSA in patients with tumors dominated by Gleason grades 3 or below, was 10 ng/ml, compared to 29 ng/ml in those with higher grades. Patients with PSA values of 50 ng/ml or above almost exclusively had tumor of Gleason grades 4 or 5, and this limit usually reflected a generalized disease. Patients with PSA-values below 10 ng/ml almost exclusively had tumors confined to the prostate gland. In countries where screening for prostate cancer is believed in, it is important to understand that normal cut-off values are related to patient's age. The upper normal limit of males below 50 years of age should be set at 2.5 ng/ml, as compared to 6.5 ng/ml for men over 70 years of age. To improve the value of PSA determination and for scientific purposes, the standardization of the assay is urgently needed and under way. Prostate acid phosphatase (PAP) has in most centres been replaced by PSA. An elevated PAP value, as measured by the enzymatic method, invariably indicates a generalized disease and could thus be used as a complementary informative assay to PSA. Other markers have been used mainly to achieve additional prognostic information. In a multivariate analysis, the non-specific tumor marker neopterin, which reflects the host response to tumor antigens, was closely related to short-term prognosis. Neopterin was followed by thymidine kinase, a protein reflecting the cell turn-over and tumor grade. Also PSA at diagnosis seemed to add some prognostic information, whereas other markers did not.

Urodynamic effects of finasteride in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia.

Urodynamic effects of the 5-alpha-reductase inhibitor, finasteride, were studied in the treatment of patients with bladder outlet obstruction due to benign prostatic hyperplasia (BPH). A total of 36 patients was randomly assigned in a double-bind manner to receive either 5 mg. finasteride daily (19) or placebo (17) for 6 months. The possible relief of bladder outlet obstruction was monitored with uroflowmetry and repeated urodynamics. The mean flow rate, detrusor opening pressure, detrusor pressure at maximum flow and maximum detrusor pressure improved significantly in the patients treated with finasteride. There were no significant differences in the improvement of symptom score or peak flow rate, or in the reduction of residual urine between the finasteride and placebo groups. The treatment resulted in 30% average decrease in prostatic size and 46% decrease in prostate specific antigen concentration. The efficacy of finasteride in relief of bladder outlet obstruction caused by BPH seems to be of the same degree as that achieved by chemical castration therapy but without any significant side effects. There were wide variations among BPH patient response to finasteride treatment. Further studies are needed to define the responders who benefit from this treatment.

Diagnostic and therapeutic aspects of adenocarcinoma of the urinary bladder.

Twenty cases of adenocarcinoma of the urinary bladder were diagnosed and treated at Oulu University Hospital between 1978 and 1991, comprising nine primary adenocarcinomas (three urachal and six non-urachal) and 11 of extravesical origin (six from the colon, four from the prostate and one from the perineal skin). The prognosis for primary adenocarcinoma after radical surgery was relatively favourable during a follow-up of mean 54 months, but extravesical origin carried a high mortality rate. The diagnostic and therapeutic aspects are discussed.

Intrascrotal adenomatoid tumors and their ultrasound findings.

Adenomatoid tumors are regarded as uncommon neoplasms of the paratesticular tissues, probably of mesothelial origin, and the majority of cases reported have involved the epididymis. Ultrasonography is the method of choice for imaging scrotal pathology, but there are very few data on ultrasound findings in cases of adenomatoid tumors. We report our experience and ultrasound findings regarding 8 intrascrotal adenomatoid tumors--3 cases of a testicular tunica albuginea tumor and 5 cases of epididymal origin. Ultrasonography is recommended as the preoperative imaging method for excluding the possibility of a cystic lesion and for determining the location of the tumor. Local excision is regarded as the treatment of choice. The clinical course of all these tumors was benign, without recurrences.

[Current methods in the treatment of prostatic hyperplasia]. / Nya metoder för behandling av prostatahyperplasi?

Prostatic hyperplasia is the most frequent disease dealt with in urological practice. Replacement of open operations by transurethral resection has resulted in a marked reduction both in morbidity and mortality, in turn broadening the indications for surgery even in cases with relatively minor symptoms. Our understanding of prostatic hyperplasia is increasing and in recent years many new options for the treatment of this troublesome disease have emerged. The article consists in a review of current thinking on prostatic hyperplasia, its diagnosis and treatment.

Efficacy and safety of bladder neck incision in patients with benign prostatic hyperplasia.

A prospective series of 104 patients underwent bladder neck incision (44 unilateral and 60 bilateral) for urinary obstruction caused by a small benign prostate enlargement. The preoperative mean peak flow value improved significantly from 11.4 ml/s to 16.2 ml/s. There were no significant differences in peak flow values between the unilateral and bilateral incision groups. Subjective results seemed to be similar but transurethral resection of the prostate was needed more often after unilateral incision than after bilateral incision. Postoperative complications were recorded only in the bilateral incision group. Altogether 62% of the patients reported changes in erection or ejaculation ability. Bladder neck incision seems to be an effective means of treating urinary obstruction but adverse effects on sexual function are common, which should be kept in mind when offering this treatment to sexually active men. It can be regarded as the treatment of choice for older men with infravesical obstruction caused by a small prostate enlargement.

Cold sensation and bladder instability in patients with outflow obstruction due to benign prostatic hyperplasia.

A series of 73 patients with bladder outflow obstruction caused by benign prostatic hyperplasia underwent urodynamic investigation, including the cold water test. The presence of detrusor instability was associated with a higher urethral opening pressure, maximum detrusor pressure and detrusor pressure at maximum flow. Instability was more common and more pronounced in patients with a lack of cold sensation, but there were some patients who, whilst lacking cold sensation, still possessed the cold reflex. This suggests partial denervation of the bladder or some form of altered modulation of sensory activity within the spinal cord or central nervous system. On the other hand, some of the patients lacked cold sensation but showed a stable detrusor and a high maximum cystometric capacity. This leads to the conclusion that there are different mechanisms by which the bladder reacts to outflow obstruction.

Recurrence of urethral stricture and late results after optical urethrotomy: comparison of strictures caused by toxic latex catheters and other causes.

During the years 1977-1985, 183 new urethral strictures were diagnosed and treated by optical urethrotomy. A sharp increase in the incidence of iatrogenic strictures was found in 1980-1981 which normalized after simultaneous changing of the resectoscope, lubricant and catheter type. In fact, an "epidemic" of urethral strictures associated with the use of indwelling latex catheters in cardiac operations was observed in Finland in those years. It is suggested that toxic latex catheters exacerbated the local mechanical injury caused by endoscopic surgery. The recurrence rate for our "epidemic" strictures was 54%, whereas in other cases it was 37% (p = 0.02), but there were no differences in the later course. The patients age, stricture site, postoperative period of catheter-drainage, length, diameter or multiplicity had no effect on the recurrence rate after the initial urethrotomy. Stricture recurrences occurred up to 8 years after the initial operation. Because of the chronic nature of the urethral stricture, a follow-up time of at least 10 years is needed before the final results of urethrotomy can be evaluated.

Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia.

The effects of finasteride, a potent 5 alpha-reductase inhibitor, were assessed in patients with benign prostatic hyperplasia. Patients were treated with finasteride or placebo for 24 weeks in a double-blind multicenter study followed by a 12-month open-extension period. After 24 weeks, finasteride-treated patients, when compared to placebo-treated patients, showed a significant reduction in prostate volume (22.5% median decrease) and prostate significant antigen (32.4% median decrease), a significant increase in maximum urinary flow (1.6 ml/s mean increase from baseline) and a significant improvement in their obstructive symptom scores (two-point decrease from baseline). Finasteride was well tolerated, and the improvements in prostate volume, maximum urinary flow rate and obstructive symptom scores observed in the controlled study were maintained throughout the extension study.

Cysts of the tunica albuginea--more common testicular masses than previously thought?

Cysts of the tunica albuginea have been considered very rare. Their clinical significance lies in their presentation as discrete testicular masses often diagnosed as malignancies prior to removal. We report our experience with 6 cases of cysts of the tunica albuginea over a 12-year period and review the relevant literature. It is obvious that these cysts can be both of epithelial and of mesothelial origin. Our material includes a cyst lined by a transitional-like epithelium, of a kind to our knowledge not reported previously. All of the cysts were found by palpation and they constituted 6% of the testicular tumours examined over the same period. High-resolution ultrasound examination can distinguish them from solid testicular masses, as in 2 cases here, thus enabling unnecessary operations to be avoided.