Changes in collagen metabolism in prostate cancer: a host response that may alter progression.

PURPOSE: The interaction of cancer cells and the extracellular matrix is essential for cancer progression. However, little is known about the influence of cancer on the metabolism of collagen, which is the major constituent of the extracellular matrix. We studied changes in collagen metabolism in prostate cancer with increasing Gleason score and correlated them with clinical parameters and patient survival. MATERIALS AND METHODS: Collagen content and clinical parameters in 3 types of prostatic tissue were compared, including the foci of prostatic cancer, unaffected tissue from the same cancerous prostates and prostatic tissue from patients with no evidence of cancer. In addition, to assess collagen metabolism tissue obtained prospectively from 45 patients undergoing prostatic biopsy was assessed for collagen content, the type and extent of collagen cross-linking, serine proteinase, matrix metalloproteinase and the C-terminal propeptide of type I collagen. RESULTS: With increasing Gleason sum of the cancer collagen content at the focus decreased, while that of surrounding unaffected tissue from the same prostate increased to levels significantly above that from controls with no cancer. Markers of collagen synthesis in the prostate biopsy material were significantly increased in the presence of prostate cancer. CONCLUSIONS: In prostate cancer there are changes in collagen metabolism not only in the cancer focus but also in nearby histologically benign prostatic tissue. These observed changes are related to the Gleason score of the tumor and may represent a host response. Collagen content in the surrounding unaffected tissue may be a predictor of patient survival.

The epidemiology and pathophysiology of erectile dysfunction.

PURPOSE: Published studies on the epidemiology of erectile dysfunction and the physiology/ pathophysiology of erectile function are reviewed. MATERIALS AND METHODS: A literature search of more than 400 studies of the epidemiology and pathophysiology of impotence and erectile dysfunction published during the last 3 decades was conducted and the most pertinent articles are discussed. RESULTS: It has been estimated that the prevalence of erectile dysfunction of all degrees is 52% in men 40 to 70 years old, with higher rates in those older than 70 years. Erectile dysfunction has a significant negative impact on quality of life. Risk factors for erectile dysfunction include aging, chronic illnesses, various medications and cigarette smoking. A nitric oxide/cyclic guanosine monophosphate mechanism has an important role in mediating the corporal smooth muscle relaxation necessary for erectile function. Other mechanisms involving neuropeptides, gap junctions and ion channels also may modulate corporal smooth muscle tone. Erectile dysfunction can be due to vasculogenic, neurogenic, hormonal and/or psychogenic factors as well as alterations in the nitric oxide/cyclic guanosine monophosphate pathway or other regulatory mechanisms, resulting in an imbalance in corporal smooth muscle contraction and relaxation. CONCLUSIONS: Erectile dysfunction is a common condition associated with aging, chronic illnesses and various modifiable risk factors. Normal penile erection is a hemodynamic process that is dependent on corporal smooth muscle relaxation mediated by parasympathetic neurotransmission, nitric oxide, and possibly other regulatory factors and electrophysiological events. As more knowledge is gained of the physiology and regulatory factors that mediate normal erectile function, the mechanisms involved in the pathophysiology of erectile dysfunction should be further elucidated.

Sildenafil: study of a novel oral treatment for erectile dysfunction in diabetic men.

The efficacy and safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, were evaluated in men with diabetes mellitus and erectile dysfunction (ED). Twenty-one men (aged 42-65 years) were enrolled in a double-blind, placebo-controlled, three-way crossover study conducted in two parts. In part I, the effect of a single dose (25 mg or 50 mg) of sildenafil or placebo on penile rigidity was assessed by penile plethysmography during visual sexual stimulation. In part II, daily diary records of erectile activity and a global efficacy question were used to evaluate once-daily dosing with 25 mg or 50 mg of sildenafil or placebo for 10 days. After a single 50 mg dose of sildenafil, the adjusted geometric mean duration (min) of penile rigidity >60% at the base of the penis during visual sexual stimulation was significantly increased (10.1 min) compared with placebo (2.8 min; p = 0.0053). In part II, sildenafil significantly increased the number of erections considered sufficiently hard for vaginal penetration compared with placebo (p = 0.0005). Improved erections were reported by 50% and 52% of patients treated with 25 mg and 50 mg of sildenafil, respectively, compared with 10% of those receiving placebo (p values < 0.05). Adverse events were mostly mild or moderate in nature and included muscular pains, headache, and dyspepsia. Sildenafil is a well-tolerated and potentially efficacious oral treatment for ED in men with diabetes mellitus.

Prophylaxis for transrectal prostatic biopsies: a randomized controlled study of intravenous co-amoxiclav given as a single dose compared with an intravenous dose followed by oral co-amoxiclav for 24 h.

OBJECTIVE: To compare in a randomized prospective study the infective complication rates of a single intravenous dose of co-amoxiclav given alone before transrectal prostatic biopsy with an intravenous dose followed by oral co-amoxiclav for 24 h. PATIENTS AND METHODS: Eighty-three patients undergoing prostatic biopsy were randomized to receive 1.2 g co-amoxiclav intravenously and then either three further doses of oral co-amoxiclav (Group 1) or no further antibiotics (Group 2). The evaluation included analysis of a mid-stream urine (MSU) sample before and 72 h after biopsy, and the recording of oral temperatures and symptoms in the first 44 patients. Patients with symptomatic urinary tract infections (UTIs), prostatitis, indwelling catheters, diabetes and those receiving steroid therapy were excluded. RESULTS: Eight patients, four from each treatment arm, were found to have asymptomatic UTIs from their MSU before biopsy. Excluding these patients, four patients (11%) from Group 1 and six from Group 2 (16%) had positive MSUs at 72 h; two patients from Group 2 and one from Group 1 required admission to hospital. Of the patients returning symptom and temperature charts, a further six (14%; three from each group) reported signs and symptoms suggestive of infection despite negative urine cultures. CONCLUSIONS: There was no statistically significant difference in the rate of positive MSUs between the groups. The incidence of infections was considerably higher than in previously published series where other antibiotics were used, suggesting that co-amoxiclav is not the drug of choice for transrectal prostatic biopsy.

Fifteen years experience of penile prosthesis insertion.

INTRODUCTION AND OBJECTIVES: To review the outcome and patient satisfaction of penile prosthesis insertion over a 15 y period. PATIENTS/MATERIALS AND METHODS: We reviewed the notes of 172 patients who underwent penile prosthesis insertion between January 1980 and May 1995. From the notes information was determined on age of the patient, type of prosthesis, surgical approach and length of stay. Also noted were risk factors for erectile dysfunction and the aetiology. Twenty patients were known to have died or moved away. To assess the impact the operation had on quality of life, 152 questionnaires were sent of which 103 were returned (67%). The questionnaire gained information about sexual activity, before and after the operation and the overall satisfaction of the patient and his partner and whether they felt the operation was a success. RESULTS: Overall 149 patients were known to have had malleable prostheses inserted and 23 had inflatables. The commonest organic groups were vascular disease, diabetes and Peyronies disease. Fifteen patients had two procedures. Four patients required revision of the prosthesis due to erosion, and there was one death due to pulmonary embolism. One hundred and three completed questionnaires have been returned to date the median time since operation was 4 y, the range being six months to 16 y and 78% thought the operation was a success. CONCLUSIONS: The insertion of malleable prostheses is associated with low complication rates, good patient satisfaction and improved quality of life for the couple. Concealment was not a major problem.

Sildenafil, a novel effective oral therapy for male erectile dysfunction.

OBJECTIVES: To determine the efficacy and safety of sildenafil, a novel orally active inhibitor of the type-V cyclic guanosine monophosphate-specific phosphodiesterase (the predominant isoenzyme in the human corpus cavernosum) on penile erectile activity in patients with male erectile dysfunction of no established organic cause. PATIENTS AND METHODS: Twelve patients (aged 36-63 years) with male erectile dysfunction of no established organic cause were entered into a double-blind, randomized, placebo-controlled, crossover study which was conducted in two phases. In the first phase (four-way crossover), treatment efficacy was evaluated by measurements of penile rigidity using penile plethysmography during visual sexual stimulation at different doses of sildenafil (10, 25 and 50 mg or placebo). In the second phase (two-way crossover), efficacy was assessed by a diary record of penile erectile activity after single daily doses of sildenafil (25 mg) or placebo for 7 days. RESULTS: The mean (95% confidence interval, CI) duration of rigidity of > 80% at the base of the penis was 1.3 min (0.4-3.1) in patients on placebo, 3.5 min (1.6-7.3; P = 0.009) on 10 mg, 8.0 min (3.7-16.7; P = 0.003) on 25 mg and 11.2 min (5.6-22.3; P < 0.001) on 50 mg of sildenafil. The mean (95% CI) duration of rigidity of > 80% at the tip of the penis was 1.2 min (0.4-2.7) on placebo and 7.4 min (2.4-8.5; P = 0.001) on 50 mg sildenafil. From the diary record of daily erectile activity, the mean (95% CI) total number of erections was significantly higher in patients receiving sildenafil was 6.1 (3.2-11.4), compared with 1.3 (0.5-2.7) in those on placebo; 10 of 12 patients reported improved erectile activity while receiving sildenafil, compared with two of 12 on placebo (P = 0.018). Six patients on active treatment and five on placebo reported mild and transient adverse events which included headache, dyspepsia and pelvic musculo-skeletal pain. CONCLUSION: These results show that sildenafil is a well tolerated and effective oral therapy for male erectile dysfunction with no established organic cause and may represent a new class of peripherally acting drug for the treatment of this condition.

Determination of prostatic volume with transrectal ultrasound: A study of intra-observer and interobserver variation.

PURPOSE: We assessed the intra-observer and interobserver variation in measurements of prostatic volume using transrectal ultrasound. MATERIALS AND METHODS: Two volume estimations were performed by 1 observer in 40 patients and by 2 observers in 75. RESULTS: Mean prostatic volumes measured ranged from 18.9 to 87.0 ml. (median 39.8) for 1 observer and from 15.5 to 95.4 ml. (median 42.4) for 2 observers. The mean difference plus or minus standard deviation and limits of agreement between the paired volume estimations were 0.1 +/- 3.3 ml. and -6.5 +/- 6.7 ml., respectively, for 1 observer, and -0.3 +/- 5.3 ml and -10.9 to 10.3 ml., respectively, for 2 observers. The mean difference was 9.8% for 2 observers. The mean difference was 9.8% for 2 observers compared to 4.6% for 1. CONCLUSIONS: The results show that there is considerable variation in repeated measurements of prostatic volume and the variation is greatest for 2 observers compared to 1 observer.

A prospective, randomised study to compare goserelin acetate (Zoladex) versus cyproterone acetate (Cyprostat) versus a combination of the two in the treatment of metastatic prostatic carcinoma.

A prospective randomised study was performed to test the hypothesis that total androgen ablation, achieved by combining an LHRH analogue, goserelin acetate (Zoladex), with an antiandrogen, cyproterone acetate (Cyprostat), is more effective than conventional monotherapy in delaying the time to progression of metastatic prostatic cancer. 525 patients were recruited at 18 UK centres between May 1986 and January 1989, 175 patients being allocated to each arm. Patients were clinically and biochemically assessed at 1, 2, 3, 6, 9 and 12 months after initiation of therapy and then every 6 months until a maximum duration of 48 months. There was no statistically significant difference in terms of median time to progression between the combination treatment arm and either monotherapy arm, although there was a statistically significant difference between goserelin acetate alone and cyproterone acetate alone, in favour of goserelin acetate (p = 0.016). All treatment regimens were well tolerated and cyproterone acetate reduced both tumour flare reactions and hot flushes in patients receiving goserelin acetate. It is concluded that total androgen ablation using cyproterone acetate (300 mg/day) and goserelin acetate (3.6 mg every 28 days) confers no advantage in terms of time to progression, to conventional monotherapy, but can reduce certain side effects caused by LHRH analogue treatment alone.

Antimicrobial prophylaxis for transrectal prostatic biopsy: a prospective randomized trial of cefuroxime versus piperacillin/tazobactam.

OBJECTIVE: To compare the clinical and microbiological outcome of a single-dose administration of cefuroxime or combined piperacillin/tazobactam (PT) after transrectal prostatic core-biopsy (TPB) in a prospective, randomized, open-label study. PATIENTS AND METHODS: Of 111 eligible men consecutively undergoing ultrasonographically guided TPB, 56 received 1.5 g cefuroxime and 55 received 4.5 g PT intravenously 20 min before the procedure. The anterior rectal wall was cleaned with an antiseptic swab and four biopsies were taken. Urine and blood cultures were evaluated before the procedure and again after 48 h, and oral temperature and symptoms recorded for 72 h after TPB. RESULTS: A clinically successful outcome (no symptoms to indicate urinary or systemic sepsis or pyrexia > or = 37.5 degrees C after TPB) was achieved in 100 of 108 men (92.6%), of whom 51 received cefuroxime and 49 PT. Microbiological success (no bacteriuria > 10(5) organisms/mL, or bacteraemia, after TPB) was observed in 98 of 103 men (95%), of whom 48 received PT and 50 cefuroxime. Bacteriuria was present 48 h after TPB in 5% of the men. One man randomized to receive cefuroxime became bacteraemic (with Escherichia coli) and required hospital admission. Four of the five microbiological failures were caused by organisms sensitive to the administered antimicrobial agent. No anaerobic organisms were cultured. The most common adverse event recorded was transient diarrhoea, reported by 16 men receiving PT and two receiving cefuroxime. CONCLUSION: With this prophylactic regimen, there was no significant difference in outcome between the groups. Most of the organisms isolated were sensitive to the administered antimicrobial agent. Thus, further reductions in sepsis after TPB may be achieved by the administration of additional oral antimicrobial prophylaxis.

Persistent spermatozoa after vasectomy: a survey of British urologists.

OBJECTIVES: To determine the rate of, and main indications for, repeat vasectomy in our department, and to assist in policy-making procedures by determining how urologists in England and Wales manage those men who show small but persistent quantities of motile or non-motile spermatozoa in their ejaculate after vasectomy. SUBJECTS AND METHODS: A retrospective review of all of the vasectomies and repeat vasectomies performed by the Urology Department at Southmead Hospital during a 14-month period was undertaken to determine the rate of and indications for repeat vasectomy. Subsequently, every consultant urologist in England and Wales was canvassed with a questionnaire to determine whether they repeated vasectomy in the presence of persistent motile or non-motile sperms and if so, after what time interval. Any experience of pregnancies arising from these groups was also assessed, and any relevant comments invited. RESULTS: The local review revealed that 5% of all vasectomies were repeated within 6-36 months. Of these, 87% were performed because of persistent sperms in post-vasectomy semen samples, the majority of which showed sperm concentrations of one in 50 to one in 100 high-power fields. A response of 56% was obtained to the questionnaire and of those responding, 23% never repeated a vasectomy where there were presistent non-motile sperms, but almost all urologists would eventually repeat vasectomy where motile sperms were present. The median interval between the first and second vasectomies was 6 months and 12 months for motile and non-motile sperm, respectively. Apart from those cases already published, there was little experience of pregnancy arising from men with persistently few motile or non-motile sperms. CONCLUSIONS: The risk of pregnancy occurring in the presence of non-motile sperms was estimated to be less than the established risk of late recanalization, and this survey provides both logical and medico-legal support for issuing a 'special clearance' to men with few persistent non-motile sperm after vasectomy, providing the risks of pregnancy are properly discussed and documented. For motile sperm, however, there appears to be a stronger precedent for repeating the vasectomy. The technique used for post-vasectomy semen analysis was also an important consideration when determining any policy regarding such cases.

A clinical evaluation of a resin-modified. Glass ionomer restorative material.

Compomers, resin-modified glass ionomers, were developed to improve the physical properties and clinical handling of glass ionomers. Compomers can be designed to be light-activated and used as restoratives or liners. This article reports data collected up to 12 months after placement of both compomer restorations and liners and is part of an ongoing study evaluating the performance of this material. Based on this data, the authors conclude that this new generation of light-activated glass-ionomer restoratives provides clinical results comparable to those recorded for composite resins at 12 months.

Placebo controlled double-blind study to test the efficacy of the aromatase inhibitor atamestane in patients with benign prostatic hyperplasia not requiring operation. The Schering 90.062 Study Group.

PURPOSE: We tested the theoretical concept that a selective decrease in estrogens has a beneficial therapeutic effect on established benign prostatic hyperplasia. MATERIALS AND METHODS: In a double-blind study 160 patients from 14 centers were randomized between 2 groups to receive either placebo or the aromatase inhibitor atamestane (1-methyl-androsin-1,4 diene-3 17-dione, 400 mg. daily for 48 weeks). RESULTS: The aromatase inhibitor decreased the mean estradiol level by approximately 40% and estrone by 60%. The testosterone concentration increased by more than 40% and dihydrotestosterone increased to 30%. Analysis of clinical parameters showed no difference between placebo and atamestane. CONCLUSIONS: The counter regulatory increase in androgens may counterbalance any positive effect of the decrease in estrogens to preserve intraprostatic homeostasis.

Prostate disease: management options for the primary healthcare team. Report of a working party of the British Prostate Group.

The prostate gland has attracted a remarkable increase in interest in the past few years. The two most common diseases of this gland, benign prostatic hyperplasia and carcinoma of the prostate, have been brought into greater prominence by new diagnostic methods, public interest, and a wider choice of surgical and non-surgical treatments. Uncertainty about the significance of these changes has occurred because of the rapidity of change, the profusion of statements, opinions and promotions, and the relatively little guidance available from the profession. Ten urologists and two general practitioners have reviewed the relevant evidence about these two prostate diseases and the newer diagnostic methods; their conclusions are summarised here. Management options and guidance on clinical practice are also discussed. Because of a number of unresolved diagnostic and management issues, detailed requirements for practice guidelines have not been specified.

Nesbit's procedure for penile curvature.

Between January 1982 and June 1992 83 patients with penile curvature due to Peyronie's disease or congenital curvature underwent a modified Nesbit's procedure for coital difficulties. This represented approximately 23% of the total number of patients referred to the male sexual dysfunction clinic with penile deformity. A confidential postal questionnaire was sent to all of the operated patients in order to determine the longterm results of surgery. Seventy-eight of the 83 patients were contacted, aged 16-71 years (mean = 48 years). Sixty-two of the 78 (79%) were satisfied with the result of surgery and would be prepared to have the operation again. Twenty-two of the 78 were not having intercourse. As a result of this survey we have identified a group of people with initial satisfactory results who have since developed erectile failure. These have been offered either self injection therapy with a vasoactive agent or penile prostheses if they do not respond or do not wish to self inject.