[Management of geriatric patients with benign prostatic hyperplasia]. / Das Management geriatrischer Patienten mit benignem Prostatasyndrom.

Multimorbid older men are increasingly more common in daily practice and present a challenge because they are often affected by lower urinary tract symptoms (LUTS) and age-associated benign prostatic hyperplasia (BPH). In order to identify possible risks in diagnostics, therapy and counselling at an early stage, screening for functional deficits or risk factors with standardized procedures is helpful. An initial screening with subsequent assessment of everyday skills using the Barthel Index, Timed up & Go Test, and a cognitive test are recommended. If frailty syndrome is detected, it should be taken into account during the pre-, peri-, and postoperative management, as it may indicate increased morbidity and mortality. Noninvasive methods for reducing the prostate volume without anesthesia can be a therapy option in older multimorbid patients, and with individual planning and consideration of risk factors, up to 70% of individuals become symptom-free. However, there is currently no gold standard for this vulnerable patient group. Number of medications and concomitant diseases and higher need for help are per se risk factors for unsatisfactory results after transurethral resection of the prostate (TURP) or laser vaporization. With drug therapy, concomitant medications and their interactions, especially in the cytochrome system, an existing multimorbidity and adherence to therapy must be taken into account. Combination therapies may complement each other and may bridge the time until surgery. Minimally invasive methods that can be performed without general anesthesia are suitable for geriatric patients, especially those with recurrent retention. Studies with the Rezüm® system (NxThera Inc., Maple Grove, MN, USA) and UroLift® (NeoTract Inc., Pleasanton, CA, USA) show that about 70% of patients can be relieved from the permanent catheter.

[Sophisticated surgical management of distinctive patients with benign prostatic hyperplasia (BPH)]. / Differenziertes operatives Management unterschiedlicher Patienten mit benignem Prostatasyndrom (BPS).

Herein we describe four clinical scenarios. For the standard patient (prostate volume 30-80 ml, life expectancy >10 years) transurethral resection of the prostate (TURP) remains the standard of care, while endoscopic enucleation is a valuable alternative. Patients with a relevant middle lobe profit most from TURP, endourological enucleation procedures, or laser vaporization. In the case of the absence or a moderate-sized middle lobe and the absence of severe bladder outlet obstruction (BOO), minimally invasive procedures such as Rezum®, UroLift® or prostate artery embolization (PAE) can be offered. Patients have to be informed that long-term data on this specific indication are lacking. Particularly younger men requiring BPH surgery are interested in preserving ejaculatory function. In the presence of severe BOO, ejaculatory-protective TURP or endoscopic enucleation by preserving the pericollicular region or aquablation are the methods of choice providing an antegrade ejaculation in 60-90% of cases. Rezum®, AquaBeam®, and UroLift® enable preservation of ejaculation in almost 100%; data on PAE with this respect are more controversial. For patients with a small prostate and significant post void residual, a thorough preoperative work-up, including urodynamics and bladder/detrusor wall thickness measurement, is of great importance. Desobstructive surgery provides satisfactory short- and midterm outcome, yet the long-term outcome is disappointing and remains to be determined in greater detail. The broad spectrum of therapeutic options enables today an individualized minimally invasive or surgical management of BPH considering patient wishes, anatomical factors or urodynamic factors. The time of a "one therapy fits all" strategy is definitely history.

[S2e guideline of the German urologists: Conservative and pharmacologic treatment of benign prostatic hyperplasia]. / S2e-Leitlinie der Deutschen Urologen : Konservative und medikamentöse Therapie des benignen Prostatasyndroms.

This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the conservative and pharmacological treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding watchful waiting, behavioral therapy, phytotherapy and pharmacological mono- and combination therapy. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.

[S2e guideline of the German urologists: Instrumental treatment of benign prostatic hyperplasia]. / S2e-Leitlinie der Deutschen Urologen : Instrumentelle Therapie des benignen Prostatasyndroms.

This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the instrumental treatment of the lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding open and transurethral procedures (TUR-P, bipolar TUR-P, TUI-P, HE-TUMT, TUNA, and the different Laser techniques). Recommendations are also given concerning intraprostatic stents and injection therapies. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.

[Phytotherapy of benign prostate syndrome and prostate cancer: better than placebo]. / Phytotherapie bei benignem Prostatasyndrom und Prostatakarzinom : Besser als Placebo?

In some countries plant extracts have belonged to the most popular drugs for the treatment of the benign prostatic syndrome (BPS) for decades; however, only few of the large number of published studies meet the criteria of the WHO benign prostatic hyperplasia (BPH) consensus conference. The few placebo-controlled long-term (study period >6 months) studies suggest a positive effect of some extracts (saw palmetto fruit, ß-sitosterol, urtica, rye grass and a saw palmetto/urtica combination) on lower urinary tract symptoms (LUTS), urinary flow rate, post-void residual volume but effects on prostate volume or prostate-specific antigen (PSA) were only inconsistently demonstrable. To date no study has proven an effect on disease progression, such as acute urinary retention or need for surgical interventions. Due to the controversial data various extraction techniques and compositions of various products, neither American, European, British nor German BPH guidelines recommend plant extracts for the indication BPS although some placebo-controlled trials provided encouraging data. Further prospective studies according to WHO standards are required to determine the role of plant extracts for the management of BPS. For the indication of prostate cancer (PCa) plant extracts have been evaluated for disease prevention and management of several tumor stages but none of these studies have provided convincing evidence that plant extracts are superior to placebo and none of the Pica guidelines have recommended their use.Based on current knowledge plant extracts can never supplement evidence-based PCa management and should be used only in addition to the standard treatment. There is no scientific evidence for the use of dietary supplementation with high doses of vitamins or selenium-containing products.

[Contemporary medical management of the benign prostatic syndrome]. / Aktuelle Aspekte der medikamentösen Therapie bei benignem Prostatasyndrom (BPS).

Two groups of drugs, alpha blockers and 5-alpha-reductase inhibitors (5ARI), are currently widely used for the medical treatment of benign prostatic syndrome (BPS). Alpha blockers are characterized by a rapid onset of efficacy. If given at an adequate dose, all alpha blockers have a similar efficacy, yet quantitative differences regarding side effects exist. The onset of clinical efficacy of 5ARIs is delayed and dependent on prostate volume. Symptom improvement is generally less pronounced than with alpha blockers, yet this difference declines with time. 5ARI, in contrast to alpha blockers, reduce prostate volume and the risk of long-term BPS complications such as prostate surgery or acute urinary retention. The combination therapy of alpha blockers and 5ARI is superior to either monotherapy; however, this superiority becomes evident only after prolonged (>1 year) therapy. Because of additive side effects, this combination should be reserved for BPS patients with a high risk of progression. Regarding plant extracts, no definitive recommendation can be given because of a limited number of high-quality clinical trials. The use of antimuscarinics in men with BPS with a dominance of storage symptoms and without significant obstruction is promising, although further trials, particularly with a longer study duration, are required.

Lower urinary tract symptoms and erectile dysfunction; links for diagnosis, management and treatment.

Recent large-scale epidemiological studies have documented a strong association between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). This observation has two important scientific and clinical aspects: (i) to reveal the pathomechanism linking LUTS and ED and (ii) to consider this fact in the individual approach for diagnosis and management of these two disorders. The following hypotheses are under investigation to explain the relation between LUTS and ED: (i) an increased Rho-kinase activation, (ii) an alpha-adrenergic receptor imbalance, (iii) a decrease of NOS/NO in the endothelium, (iv) atherosclerosis affecting the small pelvis and (v) an autonomic hyperactivity, each affecting simultaneously bladder, prostate and penis. According to a recent randomized trial, sildenafil has a positive effect on LUTS yet not on uroflowmetry in men with LUTS and ED. Although further trials are mandatory, phosphodiesterase-5 inhibitors might play a role in the management of LUTS in the future. alpha-Blockers have no relevant effect on erectile function, tamsulosin leads to retrograde ejaculation in up to 10%. 5alpha-Reductase inhibitors are associated with ED, loss of libido and reduction of ejaculate volume in up to 10%. Transurethral and open prostatectomy induce retrograde ejaculation in up to 90% of patients while their impact on erectile function is still controversially discussed. Minimal invasive treatment options (laser prostatectomy, transurethral microwave thermotherapy) have a lower rate of retrograde ejaculation in the range of 20-70%. LUTS and ED are strongly linked although the exact mechanism is poorly understood. Men seeking for help for LUTS/benign prostatic hyperplasia should be assessed for different aspects of sexual dysfunction and informed regarding the impact of medication and surgery on sexual health.

[Benign prostate hyperplasia: success and limitations of pharmacological therapy]. / Benigne Prostatahyperplasie : Erfolge und Grenzen der Pharmakotherapie.

A profound knowledge of pathogenesis and natural history enables a differentiated therapy for elderly men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH). The role of phytotherapy is still controversially discussed and, therefore, not clearly recommended by any BPH-guideline. alpha(1)-blockers are the therapy of choice for symptomatic patients at a low risk of disease progression (prostate volume <30-40 ml). 5alpha-reductase inhibitors (5ARI) reduce the prostate volume by 20-25% and the risk for acute urinary retention/surgery by more than 50% compared to placebo. Combination therapy (alpha(1)-blocker plus 5ARI) is superior to either monotherapy, though this advantage is only demonstrable after a prolonged treatment period (>12 months).

[Epidemiology of BPH and medication approaches]. / Epidemiologie der BPH und medikamentöse Ansätze.

A more profound knowledge on the pathogenesis, the natural history and the risk of progression enablesa more differentiated therapy of elderly men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) and benign prostatic enlargement as compared to 15 years ago. Phytotherapy is currently not recommended by any international BPH-guideline, because the definitive clinical proof for their clinical efficacy has not been made. alpha1-blockers and 5alpha-reductase inhibitors (5ARIs) are established world-wide. Alpha1-blockers are the medical therapy of choice for symptomatic patients with a low risk of clinical progression (e.g. prostate volume < 30-40 ml). Recent long-term data indicate that alpha1-blockers have no effect on the long-term risk of acute urinary retention and the risk of surgery. 5ARIs should be reserved for patients with a higher risk of progression (e.g. prostate volume > 30-40 ml). 5ARIs significantly reduce the risk of acute urinary retention and the need for surgery.

[Phytotherapy for BPS. Which products can still be prescribed?]. / Phytotherapie bei BPS. Welche Präparate können heute noch verschrieben werden?

For decades, plant extracts have been amongst to the most popular drugs for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH)/benign prostatic enlargement (BPE). Only a few of the many published studies meet the criteria of the WHO-BPH consensus conference. The few placebo-controlled, long-term (>/=6 months) studies suggest a positive effect of some extracts (saw palmetto, beta-sitosterol, urtica, rye-grass, saw palmetto/urtica combination) on LUTS; an effect on uroflow, post-void residual volume, prostate volume and PSA was not consistently demonstrable. Randomised trials against an active comparator (alpha1-blocker, 5alpha-reductase inhibitors) are difficult to interpret. Due to the lack of prospective studies, several meta-analyses have been published that can not, however, replace prospective studies. None of the BPH-guidelines currently recommend plant extracts, yet universally conclude that this is an interesting approach. Further prospective studies using WHO standards are required to reliably determine the role of such extracts in the management of elderly men with LUTS due to BPH/BPE.

EAU Guidelines on benign prostatic hyperplasia (BPH).

OBJECTIVE: To establish guidelines for the diagnosis, treatment, and follow-up of BPH. METHODS: A search of published work was conducted using Medline. In combination with expert opinions recommendations were made on the usefulness of tests for assessment and follow-up: mandatory, recommended, or optional. In addition, indications and outcomes for the different therapeutic options were reviewed. RESULTS: A digital rectal examination is mandatory in the assessment for the diagnosis of BPH. Recommended tests are the International Prostate Symptom Score, creatinine measurement (or renal ultrasound), uroflowmetry, and postvoid residual urine volume. All other tests are optional. The aim of treatment is to improve patients' quality of life, and it depends on the severity of the symptoms of BPH. The watchful waiting policy is recommended for patients with mild symptoms, medical treatment for patients with mild-moderate symptoms, and surgery for patients who failed medication or conservative management and who have moderate-severe symptoms, and/or complications of BPH which require surgery. Regarding non-surgical treatments, transurethral microwave thermotherapy is the most attractive option. These treatments should be reserved for patients who prefer to avoid surgery or who no longer respond favourably to medication. Finally, recommendations for follow-up tests and a recommended follow-up time schedule after BPH treatment are provided. CONCLUSIONS: Recommendations for assessment, possible therapeutic options, and follow-up of patients with BPH are made.

Management of lower urinary tract symptoms of elderly men in Austria.

OBJECTIVES: The aim of this nation-wide study was to determine the current management of elderly men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE) in Austria, and to assess changes over a 4-year study period from 1995 to 1998. METHODS: The annual figures of prostatectomies performed in Austria from 1995 to 1998 were collected from the Austrian Institute for Health Affairs. Sales figures for finasteride, alpha(1)-receptor blockers and plant extracts were obtained from IMS market sales and Austrian regional compulsory insurance companies. These data were correlated with the number of males living in Austria during the study period and to the estimated numbers of elderly men with moderate and severe LUTS in this country. RESULTS: The annual number of transurethral resections of the prostate (TURPs) decreased from 6,302 in 1995 to 5,297 in 1998 (-16%), and the number of open prostatectomies from 506 to 469 (-7%). Extrapolation of these data to 100,000 men aged > or = 55 years revealed that 0.76% underwent TURP in 1995, this figure decreased to 0.59% in 1998. Market sales of alpha(1)-receptor blockers increased by 497% during the study period and those of finasteride by 1.6%, while plant extract market sales declined by 18.2%. In 1998, plant extracts comprised 43.3% of the total BPH market, alpha(1)-receptor blockers 41.5% and finasteride 15.2%. CONCLUSIONS: During the years 1995-1998, significant changes in medical and surgical BPH therapy were observed in Austria. These data provide the basis for a comparison to the situation in other countries and serve as a baseline investigation for future studies in this country.

Two-year results of transurethral resection of the prostate versus four 'less invasive' treatment options.

OBJECTIVE: The aim of this study was to compare the efficacy or transurethral resection of the prostate (TURP) versus four less invasive treatment options during a 2-year follow-up. MATERIAL AND METHODS: 95 elderly men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) were assigned prospectively to the following five treatment arms; transurethral resection of the prostate (TURP; n = 28), transurethral electrovaporization (TUVP; n = 17), visual laser ablation of the prostate (VLAP; n = 17), transrectal high intensity focused ultrasound (HIFU; n = 20) and transurethral needle ablation (TUNA); n = 15). Preoperative workup included the International Prostate Symptom Score (IPSS), uroflowmetry, post-void residual volume (PVR), prostate volume determined by transrectal ultrasonography and a multichannel pressure flow study. Postoperative follow-up at 6, 12, 18 and 24 months included assessment of IPSS, PVR and uroflowmetry. RESULTS: At study entry, patients assigned to one of the five treatment arms were comparable with respect to age, peak flow rate (Q(max)), IPSS, prostate size and the degree of bladder outflow obstruction. During study, 1 patient in the TURP group (4%) required a secondary TURP, as compared to 23.5% (n = 4) after TUVP, 26.7% (n = 4) after VLAP, 15% (n = 4) after HIFU and 20% (n = 3) following TUNA. In patients not subjected to a secondary procedure, the IPSS decreased a mean 13. 9 after TURP, as compared to 12.7 after TUVP, 12.9 after VLAP, 7.0 after HIFU, and 9.8 after TUNA. Q(max) increased 11.5 ml/s (mean) after TURP, as compared to 11.1 ml/s after TUVP, 5.6 ml/s after VLAP, 2.5 ml/s after HIFU and 2.3 ml/s after TUNA. CONCLUSION: In up to a quarter of the patients, a secondary TURP is performed within the first 2 years after 'less invasive' procedures. These data underline the need for long-term studies to reliably assess the role of less invasive procedures and to indicate that TURP is still competitive.

Pathogenesis and management of recurrent urinary tract infection in women.

A number of pathogenic factors for the development of recurrent urinary tract infection, such as prolonged vaginal colonization with uropathogenic Escherichia coli, nonsecretion of ABH blood-group antigens, impaired local immune response, oestrogen deficiency in postmenopausal women and altered vaginal milieu caused by the use of contraceptives, are involved. Long-term use of antimicrobial agents is the cornerstone of prevention of recurrent urinary tract infection. Other approaches currently used involve self-start (on demand) therapy, oestrogen replacement in postmenopausal women, behavioural changes and alternative therapies, such as acupuncture.

Regulation of heat shock protein 27 expression of prostatic cells in response to heat treatment.

BACKGROUND: The clinical value of heat-induced coagulation of prostatic tissue is evaluated as a minimally invasive treatment for patients with benign prostatic hyperplasia (BPH) and, more recently, localized prostate cancer (PC). To obtain a more detailed insight on the effect of heat on prostatic cells, heat shock protein (HSP) 27 expression of normal and malignant prostatic cells was studied. METHODS: In vitro, HSP27 expression of prostatic stromal cells and the human prostate cancer cell line LNCaP was studied by Western blotting when cultured at 37 degrees C. Subsequently, the effect of a sublethal heat shock from 43-49 degrees C for 60 min on HSP27 expression of LNCaP was determined. In vivo, HSP27 expression pattern of nine human prostates, which were treated in vivo by thermoablation with transrectal high-intensity focused ultrasound (HIFU) 3 hr-8 days prior to surgical removal, was analyzed by immunohistochemistry. Untreated BPH (n = 10) and PC (n = 7) specimens served as controls. RESULTS: Under physiologic conditions (37 degrees C), LNCaP and prostatic stromal cells expressed a 27-kD and 56-kD anti-HSP27 reactive molecule. Following sublethal cell heating, HSP27 (27 kD) expression of LNCaP increased by 3-4-fold in a temperature-dependent manner. In untreated BPH specimens (n = 10), muscle cells stained HSP27-positive in all samples, while epithelial cells (EC) were negative in 6 out of 10 specimens. At the border of the high-intensity focused ultrasound (HIFU) necrosis, increased HSP27 expression was consistently demonstrable (n = 9). HSP27 upregulation was strongest 2-3 hr after HIFU but still demonstrable after 5-8 days. In this border zone, basal and secretory EC as well as muscle cells stained strongly for HSP27. CONCLUSIONS: Benign and malignant human prostatic cells respond to heat by increased expression of HSP27 in vitro and in vivo. Transrectal HIFU therapy induces intraprostatic thermonecrosis surrounded by a zone characterized by a massive upregulation of HSP27 expression.

[Current drug therapy of benign prostatic hyperplasia]. / Aktuelle medikamentöse Therapie der benignen Prostatahyperplasie.

Almost 60% of elderly men suffer from symptoms of BPH, which have significant impact on their daily lives. Transurethral resection of the prostate (TURP) is currently the most effective therapy for relieve of obstruction and obstructive symptoms. Morbidity of TURP and disappointing results in patients with mild or moderate symptoms make surgery not suitable for all patients. 2 groups of drugs were currently developed, and showed efficacy in double-blinded placebo-controlled studies: alpha-blocking agents and 5 alpha-reductase inhibitors. Inhibition of alpha-adrenoreceptors significantly increases urinary flow rates and improves symptoms of BPH. Long-acting drugs, who selectively block alpha 1-adrenoreceptors (terazosin, doxazosin, tamsulosin) have the advantage, when compared with non-selective-alpha-blockers, that they have generally less adrenergic side effects. After intake alpha-adrenorceptor antagonists develop almost immediate action. 5 alpha-reductase inhibitors (finasteride) reduce prostatic size by 27%, they increase urinary flow rates and improve prostatic symptom scores, whilst adverse effects are extremely low. Full medical action is after 4 to 6 weeks. Both, alpha-Blockers and 5 alpha-reductase inhibitors need permanent administration for maintenance of action. Yet, synergistic effects, using their different modes of action have not been demonstrated after application of both drugs. Herbal products have not proved efficacious inspite of singular surprising results in clinical trials, their efficacy to treat BPH related symptoms was classified as placebo alike. Prior to therapy urological diagnosis and exclusion of prostate cancer is mandatory. Pharmacotherapy with alpha 1-adrenoreceptor antagonists and 5 alpha-reductase inhibitors have a place in the management of BPH patients with mild to moderate disease, who are bothered by their symptoms, or for those awaiting or wishing to delay surgery.

[Minimal invasive therapy of benign prostatic hyperplasia]. / Minimal invasive Therapie der benignen Prostatahyperplasie.

Within the past decade, a number of minimally invasive treatment alternatives to transurethral resection of the prostate (TUR/P) have been developed. The majority of these techniques make use of the therapeutic effect of heat with a close correlation of therapeutic heat and clinical efficacy, yet also postoperative morbidity. Therapeutic temperatures below 45 to 47 degrees C ("hyperthermia") do not induce irreversible tissue destruction and are therefore obsolet. Temperatures in the range of 47 and 60 degrees C ("thermotherapy") lead to irreversible tissue destruction. Between 60 and 200 degrees C ("thermoablation") cystic cavities, comparable to post-TUR/P effects, can be seen. Even higher temperatures lead to tissue vaporisation and are used for laser-prostatectomy and electrovaporisation of the prostate. Although randomised phase-III clinical trials are available for some of these techniques, it is too early to make a definitive judgement concerning their future role in the armentarium for BPH-treatment. Finally, it needs to be emphasized that the golden standard for BPH-therapy is TUR/P.

Tissue ablation in benign prostatic hyperplasia with high-intensity focused ultrasound.

The safety and effectiveness of tissue ablation by coagulative necrosis with high-intensity focused ultrasound (HIFU) applied through a rectal probe to 36 patients with symptomatic benign prostatic hyperplasia (BPH) was investigated in a phase II clinical trial. Overall, HIFU treatment was well tolerated, the mean hospital stay being 1.1 days. Negative side effects were transient urinary retention in 32/36 patients, hematuria in 2 patients and hematospermia resolving after 3-4 weeks (n = 15). After 3 months the maximum flow rate/s (Qmax) increased from 9.0 +/- 3.9 to 14.4 +/- 7.0 ml/s, the median flow rate/s (QM90) from 4.9 +/- 2.4 to 7.6 +/- 4.17 ml/s; the postvoid residual volume decreased from 128 +/- 88 to 57 +/- 35 ml and the AUA symptom score from 25.5 +/- 5 to 13.2 +/- 4.4. In conclusion, it was shown that tissue ablation in patients with symptomatic BPH using HIFU is safe and dramatically reduces both obstructive and irritative symptoms and leads to a significant increase in uroflow and a decrease in postvoid residual volume.

Morphology of tissue destruction induced by focused ultrasound.

The effect of high-intensity focused ultrasound (HIFU) ablation on the morphology of prostatic, renal and testicular tissue was studied by light and electron microscopy. Specimens were obtained in 21 patients 1 h to 10 weeks after lesioning. Histological findings showed consistent coagulative necrosis with precisely defined, sharp margins to normal tissue. Lesion size and position correlated well with the assumed target zones, suggesting that HIFU permits therapeutic tissue ablation.