PDE5 inhibitors in the treatment of LUTS.

Both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) have a negative impact on patients' quality of life. The co-prescription of two active agents for these conditions will improve each condition and the addition of one drug to the other may potentiate the primary response of the first treatment and thereby improve the QoL of patients. Several epidemiological studies have indicated that the association between LUTS and ED is more than a co-incidence of age, with a possible cause and effect relationship. LUTS is more common in men with ED and there is a strong relationship between the severity of LUTS and the degree of erectile difficulty. Four pathophysiologies have been suggested to explain the relationship between LUTS and ED. There is a complex interaction between these mechanisms and there may be additional processes involved. These are: (1) alteration in nitric oxide levels; (2) autonomic hyperactivity; (3) changes in the Rho-kinase/endothelin pathway; and (4) pelvic vasculature atherosclerosis. Studies of all three easily available PDE-5 inhibitors have shown improvements in both LUTS and ED in men with significant problems in both areas without any substantial increase in side effect profile. Studies have also shown that the greatest improvements occurred with the combination of an alpha blocker and PDE-5 inhibitor when compared with either drug alone. Whilst significant improvements were seen in LUTS symptom scores, there was no significant improvement in flow rates with PDE-5 inhibitors when compared with placebo. High quality basic science studies of PDE-5 inhibitors on bladder muscle and alpha blocker agents on penile cavernosal tissue have provided several explanations for their modes of action. Even so, the mechanism of action of PDE-5 inhibitors in LUTS remains far from certain. More well-designed, placebo-controlled studies are needed to confirm the impact of these drugs, alone or in combination, on both ED and LUTS. However combination therapy appears appropriate for patients with both LUTS and ED. At present though, we should not routinely offer a combination of PDE-5 inhibitors and alpha blocker for the treatment of LUTS alone.

Splenogonadal fusion - not just another hydrocoele.

Splenogonadal fusion is a rare congenital abnormality. In this case report, the diagnosis of splenogonadal fusion was made after the removal of an abnormal mass at 'routine' left herniotomy. A cautious approach at surgery resulted in no apparent damage to the testicle. A short review of the literature is included.

Nephrostomies in obstructive uropathy; how should hormone resistant prostate cancer patients be managed and can we predict who will benefit?

Current opinion advocates the use of nephrostomies in hormone naive patients with obstructive uropathy while hormone resistant patients require an individual approach. Patients undergoing a nephrostomy for uropathy were retrospectively analysed, with particular interest in hormone status and blood levels. Over a 46-month period, 26/112 nephrostomies were performed for prostate cancer induced uropathy. Survival was 226.5 days for hormone naive patients, 114.3 days in the responsive group and 100.2 days if resistant. Bilateral cases survived 72.1 days versus 157.6 days for unilateral patients. All patients should be considered for nephrostomy despite their hormone status.

Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care--the Triumph project.

OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the most common conditions associated with ageing in men. BPH often presents as lower urinary tract symptoms (LUTS) due to difficulties in voiding and irritability of the bladder. We conducted a retrospective cohort study within the Integrated Primary Care Information (IPCI) database, a general practitioners database in The Netherlands, to assess the incidence of LUTS suggestive of BPH (LUTS/BPH) in the general population. MATERIALS: Our study population comprised all males, 45 years or older who were registered for at least 6 months prior to start of follow-up. The study period lasted from 1 January 1995 to 31 December 2000. Cases of LUTS/BPH were defined as persons with a diagnosis of BPH, treatment or surgery for BPH, or urinary symptoms suggestive of BPH that could not be explained by other co-morbidity. RESULTS: The study cohort comprised 80,774 males who contributed 141,035 person-years of follow-up. We identified 2181 incident and 5605 prevalent LUTS/BPH cases. The overall incidence rate of LUTS/BPH was 15 per 1000 man-years (95% CI: 14.8-16.1). The incidence increased linearly (r(2) = 0.99) with age from three cases per 1000 man-years at the age of 45-49 years (95% CI: 2.4-3.6) to a maximum of 38 cases per 1000 man-years at the age of 75-79 years (95% CI: 34.1-42.9). After the age of 80 years, the incidence rate remained constant. For a symptom-free man of 46 years, the risk to develop LUTS/BPH over the coming 30 years, if he survives, is 45%. The overall prevalence of LUTS/BPH was 10.3% (95% CI: 10.2-10.5). The prevalence rate was lowest among males 45-49 years of age (2.7%) and increased with age until a maximum at the age of 80 years (24%). CONCLUSIONS: The incidence rate of LUTS/BPH increases linearly with age and reaches its maximum at the age of 79 years.

Lower urinary tract symptoms suggestive of benign prostatic obstruction: what is the available evidence for rational management?

Because of the need for a more rational management of LUTS suggestive of BPO, EBM is receiving more attention. Treatment decisions should be based on scientific evidence more than on personal preferences of physicians and patients. EBM is more than following rigid treatment guidelines or published advice. It is a process of turning problems of clinical practice into well-defined questions and then finding and appraising available evidence and implementing it into clinical practice. In cases of LUTS suggestive of BPO, much evidence is available on the efficacy and tolerability of different treatment modalities in the short term, whereas long-term data on (cost)-effectiveness are rather scarce. From a patient's point of view, newer pharmacotherapeutic agents can be considered as an appropriate treatment option. alpha(1)-Adrenoceptor antagonists seem to be more efficacious than finasteride and within this group of drugs, selective alpha(1A)/alpha(1D)-adrenoceptor antagonists particularly show a favourable efficacy/tolerability ratio.

Initial choices and final outcomes in lower urinary tract symptoms.

Management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) requires careful thought so that the most appropriate treatment can be targeted to each individual patient. Initial choices in the management of LUTS/BPH include watchful waiting, medical therapies and surgical interventions. A decision on treatment choice should be taken together with the patient. It should be based on the best available scientific evidence but also be individualised to patients' circumstances and personal choices. Management of LUTS/BPH should be focused on the burden and impact of urinary symptoms and related quality of life. The rate of treatment failure, which can be assessed through the switch to other medical therapy or surgery and/or the delay or prevention of complications related to LUTS/BPH, is also important. Beneficial effects of treatment should be balanced against the incidence of adverse events associated with therapy. Medical therapy has been shown to be effective in improving short-term outcomes (maximum urinary flow rate and symptom scores). Increasing evidence indicates that in the long-term more selective alpha(1)-adrenoceptor (AR) antagonists such as alfuzosin and tamsulosin may reduce the risk of treatment failure with a comparable rate to finasteride. Although the different alpha(1)-AR antagonists are equivalent in efficacy they differ in tolerability with the subtype selective tamsulosin having the lowest risk for interference with blood pressure regulation. Transurethral resection of the prostate (TURP) improves storage symptoms to a lesser extent and/or more slowly than it improves voiding symptoms. In contrast, alpha(1)-AR antagonists improve both voiding and bothersome storage symptoms to the same extent and quite rapidly which has a considerable impact on quality of life. alpha(1)-AR antagonists also relieve storage symptoms to almost the same extent as TURP. Ultimately the initial choice of treatment will depend upon its efficacy, speed of onset, durability, tolerability and on patients' choice. For the majority of patients with moderate to severe symptoms a subtype selective alpha(1)-AR antagonist such as tamsulosin offers the best current combination of efficacy and tolerability.

Sildenafil citrate (Viagra) is effective and well tolerated for treating erectile dysfunction of psychogenic or mixed aetiology.

Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction (ED) of organic aetiology. This study assessed the efficacy and tolerability of sildenafil for treating ED of psychogenic and mixed psychogenic/organic aetiology. Men with ED of psychogenic and mixed aetiology were randomised in a double-blind, fixed-dose study to placebo (n = 95) or sildenafil 10 mg (n = 90), 25 mg (n = 85), or 50 mg (n = 81) once daily for 28 days. Efficacy was evaluated with two global efficacy questions, a patient log of erectile activity, a sexual function questionnaire and a partner questionnaire. Patients receiving sildenafil had significantly more grade 3 (hard enough for penetration) or grade 4 (fully hard) erections per week than patients receiving placebo, and a greater proportion of patients receiving sildenafil reported that treatment had improved their erections (p < 0.001). Results of the sexual function questionnaire demonstrated significant improvement for patients with ED receiving sildenafil compared with patients receiving placebo for frequency, hardness and duration of erections (p < 0.01), and for enjoyment of sexual intercourse and satisfaction with sex life (p < 0.05). The results of the partner questionnaire were consistent with the results reported by patients and showed that treatment with sildenafil was associated with significant improvement in the partners' own sex lives (p < 0.001). Adverse events were mostly mild to moderate in nature. The commonest adverse events were headache, dyspepsia, flushing, myalgia, arthralgia and flu syndrome. Discontinuations due to treatment-related adverse events were few, ranging from 1.1% to 6.2% for patients receiving different doses of sildenafil and 4.2% for patients receiving placebo. Sildenafil is an effective and well-tolerated treatment for ED of psychogenic or mixed aetiology with once-daily dosing.

Tamsulosin: 3-year long-term efficacy and safety in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction: analysis of a European, multinational, multicenter, open-label study. European Tamsulosin Study Group.

OBJECTIVE: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) treated for up to 3 years. METHODS: Patients were enrolled from two European, 12-week, placebo-controlled trials. This analysis reports on 355 patients randomized originally to tamsulosin (n = 244) or placebo (n = 111) in the two placebo-controlled trials with follow-up data for up to 3 years. RESULTS: The significant improvements in the primary efficacy parameters, maximum urinary flow rate (Q(max)) and total Boyarsky symptom score that were observed during the placebo-controlled trials were sustained throughout the long-term extension study for up to 3 years in patients who remained on therapy. Mean Q(max) increased from baseline (range 0.7-1.8 ml/s; p < 0.05 vs. baseline) and remained between 11.5 and 12 ml/s during the entire follow-up period. Total Boyarsky symptom score also improved from baseline (range -3.7 to -4.1 (or -39 to -44%); p < 0.001 vs. baseline). Similarly, the percentage of treatment responders, defined as an increase in Q(max) of >/=30% or a decrease in total symptom score of >/=25%, remained constant throughout the 3-year period. The number of patients who had a clinically significant total Boyarsky symptom score response ranged between 69 and 80%. During the 3-year study period, 95 patients (27%) experienced an adverse event considered to be possibly or probably related to study medication, the most common of which (occurring in

Who should be treated and how? Evidence-based medicine in symptomatic BPH.

The management of benign prostatic hyperplasia (BPH), although based on the best available evidence, should be individualised to patients' circumstances and personal choices. Subjective symptoms (LUTS), bothersomeness and negative impact on the quality of life are the main reasons for the patient to seek treatment for BPH. Therefore, the improvement of this subjective discomfort ought to be an important treatment goal and criterion of appraisal. Although transurethral resection of the prostate (TURP) remains the most effective and definite way of treatment, it is less attractive from the patients' perspective, especially after medical treatments with better tolerability have become available. For this reason, the indication for surgery is nowadays set on more stringent criteria of 'appropriateness'. Several new, less-invasive surgical techniques have been introduced, but their ultimate position is difficult to appraise because of the lack of appropriate long-term data from prospective, properly designed, controlled trials, also in terms of lack of data on cost-efficiency. Therefore, medical therapy with either finasteride or alpha(1)-blockers remains an attractive therapeutic alternative: both approaches are effective, reasonably well tolerated and in the 'shorter' term more cost-efficient than TURP. Available evidence suggests that finasteride is mainly effective on a long-term basis in patients with substantially enlarged prostates. In the shorter term, alpha(1)-blockers have consistently been shown to be more effective than finasteride, irrespective of prostate size. In addition, alpha(1)-blockers have the important advantage of a rapid alleviation of subjective discomfort. To date, the combination of an alpha(1)-blocker and finasteride seems to offer no more than an alpha(1)-blocker alone. Among the alpha(1)-blockers, tamsulosin is particularly suited because of its clinical selectivity (i.e. its low risk of safety relevant cardiovascular effects) and its ease of use (once daily administration without the need for stepwise dose increments on treatment initiation). Copyrightz1999S.KargerAG,Basel

Tamsulosin 0.4 mg once daily: effect on sexual function in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.

OBJECTIVE: To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). METHODS: Data from 830 patients randomized into three European multicenter studies with similar protocols were analyzed. In two studies, patients were randomized to receive either tamsulosin, 0.4 mg once daily, or placebo, and in the third, patients were randomized to receive either a fixed dose of tamsulosin, 0.4 mg once daily, or alfuzosin, titrated to 2.5 mg three times daily. The studies employed a 2-week placebo run-in period, followed by a 12-week study period. Sexual function was assessed by related adverse events and by a sexual function score determined from a life-style questionnaire. RESULTS: Abnormal ejaculation occurred significantly more frequently in patients treated with tamsulosin than in those receiving placebo (p = 0.045); however, the incidence of abnormal ejaculation was similar in patients receiving tamsulosin or alfuzosin in the comparative study. Abnormal ejaculation was not perceived as a major problem by the patients since it resulted in few treatment discontinuations (n = 3). It was also reversible on drug withdrawal. There was no difference between tamsulosin and placebo or alfuzosin with regard to the occurrence of decreased libido or impotence. In addition, there was no significant difference in the change in sexual function score between patients treated with tamsulosin and those treated with alfuzosin. Compared with patients receiving placebo, there was, however, a significant improvement in total sexual function score in patients receiving tamsulosin (p = 0.042). CONCLUSIONS: Tamsulosin, 0.4 mg once daily, is well tolerated and has no overall negative impact on sexual function compared with placebo or alfuzosin. Compared with placebo, tamsulosin may even improve sexual function.

The use of generic measures of health-related quality of life in the assessment of outcome from transurethral resection of the prostate.

OBJECTIVES: To investigate the performance of the EuroQol (EQ) quality-of-life measure and the Nottingham Health Profile (NHP) in assessing the outcome of transurethral resection of the prostate (TURP) for lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO), and to determine which men experience the greatest increase in health-related quality of life (HRQL) after TURP. PATIENTS AND METHODS: A prospective cohort study was undertaken over 12 months from Arpil 1992 of 314 men who completed the EQ, the NHP and a symptom inventory before undergoing elective TURP for probable BPO (Group 1). Identical postal questionnaires were used to follow up this group at 6 weeks, 6 months and 12 months post-operatively, with response rates of 79%, 74% and 69%, respectively. Overall, 92% of patients responded at either 6 or 12 months after surgery. A group of 51 men who had not undergone operation, also with LUTS and probable BPO, were similarly followed over 6 months, before eventually undergoing TURP (Group 2). These patients differed from Group 1 in being younger, less symptomatic and having a higher baseline quality-of-life score, but the inclusion of this group from a broadly similar diagnostic category allowed outcome to be assessed over time in the absence of surgery. RESULTS: There was a significant improvement in all LUTS 6 weeks after TURP; post-micturition dribbling and storage symptoms continued to improve for up to one year. The NHP revealed pre-operative morbidity in all dimensions of the profile. At 12 months after surgery there were significant improvements in the domains of social interaction, energy, pain, emotional reactions and sleep. The EQ profile also showed morbidity in all dimensions before surgery, with significant improvement at 12 months in usual activities, mood and pain/discomfort. The EQ self-rated health and composite quality-of-life score also showed improvement with TURP which continued for 12 months after surgery. The patients in Group 2 tended to deteriorate over the 6 months of follow-up using all measures, but the changes were not significant. The EQ composite quality-of-life score also discriminated between patients on the basis of age, number of symptoms and ASA grade, suggesting that these subgroups experienced differing amounts of benefit from surgery. CONCLUSION: TURP led to significant improvement in the indices of generic HRQL as measured using the NHP and EQ; this improvement continued for 12 months after surgery and mirrored the symptomatic improvement. The EQ confirmed clinical experience, in that men who were younger, fitter and most symptomatic experienced the greatest benefit from surgery. This has not been shown previously using a quality-of-life measure. Generic HRQL measures can be incorporated easily into clinical trials and both the measures used in this study have sufficient sensitivity to be used in this population. The EQ has the advantage of generating a composite quality-of-life score which is easy to interpret and can be used in cost-utility analysis. The addition of HRQL measures leads to a more robust appraisal of the results of surgical intervention. Ultimately, patient-based outcome from TURP will be assessed using a combination of psychometrically tested disease-specific and generic measures, together with symptom scoring.

Multiple use of fibres in the visual laser ablation of the prostate.

OBJECTIVE: To investigate the possibility of re-using laser fibres for the visual laser ablation of the prostate (VLAP). PATIENTS AND METHODS: Thirty-four patients, each with a mean maximum urinary flow rate of < 14.0 mL/s and an American Urological Association symptom score of > 19, were evaluated. All underwent VLAP: laser energy, generated by a Neodymium:YAG system, was delivered with a side-firing fibre. The laser generator was fitted with a custom-built power meter that measured the energy delivered by the fibre. Fibres were re-used until the energy output fell below 60 W despite increases in laser generator power. Each patient was followed for at least 12 months. RESULTS: A total of seven fibres was used to treat the 34 patients; between one and nine patients were treated with each fibre. The outcome obtained with the first use of a fibre compared well with those obtained with each subsequent use. After 12 months, 25 patients (74%) expressed satisfaction with the results of their operation. Five patients (15%) had urinary tract infections. As each fibre costs about pound 650, multiple use saved a mean of pound 516 for each patient treated. CONCLUSION: This evaluation implies that there is no justification for the single use of laser fibres on the basis of efficacy, provided that a power meter is used to monitor the efficiency of the delivery device.

Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. Analysis of a multinational, multicentre, open-label study assessing the long-term efficacy and safety in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin Study Group.

OBJECTIVE: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with benign prostatic enlargement, lower urinary tract symptoms and benign prostatic obstruction (symptomatic BPH) for up to 60 weeks. METHODS: Patients were enrolled from two European, 12-week, placebo-controlled trials. This 60-week interim analysis includes the patients (n = 244) randomized to tamsulosin in the two placebo-controlled trials. RESULTS: The significant improvements in the primary efficacy parameters, maximum urinary flow rate (Qmax) and total Boyarsky symptom score, that were observed during the placebo-controlled trials, were sustained throughout the long-term extension study. Mean Qmax improved from baseline (before initiation of tamsulosin) to endpoint by 13.7% (p < 0.001) and remained between 11.5 and 12 ml/s during the entire follow-up period. Total Boyarsky symptom score improved by 36.2% from baseline to endpoint (p < 0.001). Similarly, the percentage of treatment responders, defined as an increase in Qmax of > or = 30% or a decrease in total symptom score of > or = 25%, remained constant throughout the 60-week period. At endpoint, 69% of patients demonstrated this clinically significant total Boyarsky symptom score response. During the 60-week study period, 51 patients (21%) experienced an adverse event considered to be possibly or probably related to study medication, the most common of which were dizziness and abnormal ejaculation, both occurring in 5% of patients. There were no clinically significant changes in blood pressure or pulse rate during the study. CONCLUSION: Long-term tamsulosin therapy is safe, well tolerated and improvements in urinary flow and symptoms are maintained for at least 60 weeks of treatment.

Appendicovesical fistula.

In this study, a case of appendicovesical fistula is introduced, a really uncommon complication of acute appendicitis. This special case joins the other 102 cases which have already been described in the international literature. Due to the mild and ambiguous symptomatology, the diagnosis of this kind of fistula is difficult to be confirmed, although a serious suspicion of a vesicointestinal communication does exist. Exploratory laparotomy is usually diagnostic and leads to decisive therapy. A brief review of this clinical entity is also included.

Chronic scrotal pain. A study of its causes and management.

Chronic scrotal pain is a common complaint that always causes anxiety to the patient, frequently causes diagnostic difficulties to the general practitioner and usually results in prolonged follow-up in surgical clinics. Careful examination in a urological clinic and ultrasound study in all patients reveals a firm diagnosis in 60%, and the other patients can be reassured and discharged from surgical follow-up, although 19% of them will remain symptomatic.

Skin chordee without hypospadias--an under-recognised entity.

Skin chordee is a congenital abnormality due to failure of development of the mesenchyme surrounding the primitive urethra. It is frequently misdiagnosed as hypospadias. We describe the presentation and surgical management of 12 patients who presented to this hospital over the past 3 years.

First clinical report of a new biodegradable membrane for use in urological surgery.

Following preliminary in vitro and in vivo experiments a new collagen Vicryl mesh has been devised. The membrane has been extensively tested in the laboratory and has been found to resist the passage of urine. It holds sutures well and has been shown on an experimental animal to be biodegradable. The membrane has now been applied in human subjects. It has been particularly efficacious in renal surgery and as a means of sealing a bladder after it has been opened. With respect to the ureter the sealing effect is excellent, to the extent of having produced a urinoma. The membrane has been found to be easily applied in vesicovaginal fistulae but difficulties have been experienced in the presence of infection. It is also an ideal membrane for repair of a urethrovaginal fistula--an area where natural tissues are less easily available. This is the first recorded use of this new biodegradable membrane in the human subject.

Cystometric, physiological and morphological studies after relief of bladder outflow obstruction in the pig.

Experimental bladder outflow obstruction was relieved in 18 pigs between 2 and 15 months after the creation of partial urethral obstruction. Cystometric, physiological and morphological studies were performed 2 to 6 months after relief of the obstruction. An increase in average voiding flow rates from 2.8 +/- 1.0 ml/s to 6.8 +/- 1.2 ml/s was recorded in the Landrace pigs and from 2.2 +/- 0.9 ml/s to 7.4 +/- 1.4 ml/s in the Göttingen mini-pigs. There was a concomitant decrease in the voiding detrusor pressures from 52 +/- 11 cm H2O to 32 +/- 8 cm H2O and from 78 +/- 12 cm H2O to 33 +/- 6 cm H2O respectively. A return towards control values of the physiological responses to exogenously applied agonists (acetylcholine and potassium) and to electrical field stimulation was observed. There was an increase in neuronal innervation in the morphological studies which was more marked in the animals with a shorter period of obstruction. The implications for patient care are discussed.