Impact of desmopressin on nocturia due to nocturnal polyuria in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH).

PURPOSE: To evaluate the efficacy of desmopressin on nocturia, quality of sleep (QoS), and health-related quality of life (HRQoL) in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and nocturia due to nocturnal polyuria (NP) as the predominant symptom. METHODS: A German observational, multicenter, post-marketing surveillance study including men with LUTS/BPH and nocturia due to NP starting 3 months of desmopressin treatment. RESULTS: In total, 137 patients with a mean of 3.8 nocturnal voids (range 2-7) were included. Desmopressin significantly reduced the mean number of nocturnal voids by 53 %, mean IPSS nocturia question by 50 %, and the mean ratio of night/24-h urine volume by 39 % from baseline to endpoint. The hours of undisturbed sleep significantly increased by 74 %; 71 % of men reported about undisturbed sleep of ≥4 h at study end. Additionally, there was a significant reduction in the Leeds Sleep Evaluation Questionnaire score, indicating a clinically relevant QoS improvement. This was associated with an improved HRQoL, as shown by a significant improvement in both the mean IPSS-QoL question by 43 % and mean ICIQ-N nocturia problem question by 53 %. Concomitant alpha-blocker use had no effect on the efficacy of desmopressin. The incidence of adverse events was low (2.2 %). Hyponatremia was not observed in any patient. The majority of patients and physicians rated the efficacy and tolerability of desmopressin as good/very good. CONCLUSIONS: Desmopressin is an effective and well-tolerated treatment for nocturia due to NP in patients with LUTS/BPH in daily practice under routine conditions.

[Minimally invasive treatment of benign prostatic hyperplasia : The German S2e guideline 2023-part 4]. / Minimalinvasive Therapien des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 ­ Teil 4/4.

BACKGROUND: Lower urinary tract symptoms suggestive for benign prostatic obstruction (LUTS/BPO) are one of the most frequent diseases in men and can have a significant impact on quality of life. Instrumental therapies are common, and many patients seek minimally invasive treatment options. OBJECTIVE: Presentation and evidence-based evaluation of the minimally invasive therapy for benign prostatic syndrome. MATERIALS AND METHODS: Summary and overview of chapters 11-13 on minimally invasive therapies for LUTS/BPO of the current long version of the German S2e guideline. RESULTS: In case of absolute indication for surgery or after unsatisfactory or undesired medical therapy, minimally invasive treatments such as UroLift® (Neotract Inc., Pleasanton, CA, USA), Rezá¿¡m™ (Boston Scientific, Malborough, MA, USA), iTIND™ (Olympus America Inc., Westborough, MA, USA), and prostatic artery embolization (PAE) can be considered. These indirect/delayed ablative therapies offer lower morbidity and the possibility of performing them under local anesthesia, but they are inferior to direct ablative/resective techniques in terms of effectiveness and sustainability. CONCLUSIONS: The updated German S2e guideline summarizes evidence-based recommendations for new minimally invasive therapies for LUTS/BPO, which present alternative treatment options for selected patients.

[Diagnostic work-up of benign prostatic hyperplasia : The German S2e-guideline 2023 part 1]. / Diagnostik des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 Teil 1.

BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; in German guidelines: benign prostatic syndrome [BPS]) is the most frequent urological disease in men and can result in a considerable deterioration of quality-of-life. BPS can be associated with LUTS, benign prostatic enlargement (BPE), and bladder outlet obstruction (BOO) or benign prostatic obstruction (BPO), respectively. The expert group on BPS of the German Society of Urology has re-evaluated the tests for the assessment of BPH and provides evidence-based recommendations. OBJECTIVES: Presentation and evidence-based rating of tests for the assessment of patients with BPS. MATERIALS AND METHODS: Summary and overview of chapters 5, 6, and 8 of the latest long version of the German S2e guideline on BPS. RESULTS: The diagnostic work-up should clarify (1) whether the complaints of the patient are caused by BPS, (2) how relevant the complaints are and whether treatment is necessary, (3) whether complications of the lower or upper urinary tract already exist, and (4) which treatment will be most suitable. Baseline assessment should be done in all BPS patients and include history, measurement of LUTS and quality-of-life, urinalysis, serum prostate-specific antigen, post-void residual, ultrasound of the lower urinary tract, including measurements of prostate volume, intravesical prostatic protrusion and detrusor wall thickness, and ultrasound of the upper urinary tract. Additional tests can follow when questions remain unanswered after baseline assessment. These optional tests include bladder diaries, uroflowmetry, serum creatinine, urethrocystoscopy, other noninvasive tests for the determination of BOO/BPO such as penile cuff test, condom catheter method and near-infrared spectroscopy, and other imagining tests such as X­ray and MRI investigations. CONCLUSIONS: The updated German S2e guideline summarizes evidence-based recommendations on the diagnostic work-up, including the assessment of the BPS components BPE, LUTS, and BOO/BPO.

[Conservative and pharmacological treatment of benign prostatic hyperplasia : The German S2e-guideline 2023-part2]. / Konservative und medikamentöse Therapie des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 ­ Teil 2.

BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH, in German guidelines: benign prostatic syndrome [BPS]) is considered the most common disease of the lower urinary tract in men and can have a tremendous impact on the quality-of-life of affected patients. Conservative and pharmacological therapy of this disease are of great importance, both in improving LUTS and reducing progression-related complications. OBJECTIVES: Presentation of the conservative and pharmacological treatment options according to the current German S2e guideline on BPS. MATERIALS AND METHODS: Summary and overview of chapters 9 and 10 of the current German S2e guideline on BPS. RESULTS: In addition to a controlled watchful waiting for BPS patients without an absolute indication for prostate surgery, a variety of phytopharmacological formulations and synthetic drugs according to the symptomatology and clinical progress are available. Phytotherapy should, due to inconsistent study data, only be considered for mild to moderate symptoms. Synthetic drugs include alpha-blockers, 5α-reductase inhibitors, phosphodiesterase inhibitors, antimuscarinics and, more recently, the ß3-agonist mirabegron in the current guideline. In addition, various combination therapies are listed and evaluated according to their indications, effects and side effects. CONCLUSIONS: The current German S2e guideline on the diagnosis and treatment of BPS provides an evidence-based foundation for finding the best possible and most effective medication.

[Surgical treatment options of lower urinary tract symptoms due to benign prostatic obstruction : The German S2e guideline 2023-part 3]. / Operative Therapie des benignen Prostatasyndroms ­ klassische Desobstruktion : Die deutsche S2e-Leitlinie 2023 ­ Teil 3.

BACKGROUND: Lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) are one of the most common diagnoses in clinical practice. Bothersome LUTS impact considerably quality of life of men and may cause severe complications without treatment. According to the diagnostic assessment every patient should be treated with an adequate therapy. Management comprises a conservative approach, medication, novel minimally invasive options, and surgical procedures with the aim to remove the obstructing adenoma. The German guideline panel has updated the German guidelines on diagnostic evaluation and management of LUTS due to BPO. OBJECTIVES: Evidence-based recommendations of surgical treatment options of LUTS due to BPO are evaluated. MATERIALS AND METHODS: Chapters 11.1.1 and 11.2 of the updated German S2e guideline on the management of LUTS due to BPO are summarized as a review article. RESULTS: A treatment algorithm based on current evidence has been proposed. It is considered to provide guidance for the selection of the best procedure according to the needs of the patient. Anatomic features of the prostate, the patients' morbidity, and the preservation of ejaculatory function are taken into account for the choice of the best procedures. These surgical options can be divided into techniques with direct, delayed or no removal of the adenoma, procedures with suprapubic access, and embolizing approaches. CONCLUSIONS: The updated German S2e guideline on the management of LUTS due to BPO provides evidence-based recommendations for the selection of the best procedure according to the needs of the individual patient.

The fish-hook configuration of the distal ureter indicates bladder outlet obstruction due to benign prostatic hyperplasia.

PURPOSE: The aim of this retrospective study was to evaluate in a historical series of patients whether morphological changes of the urinary tract imaged on intravenous urography (IVU) are associated with clinical or urodynamic data. METHODS: During a 1-year period, every man 45 years or older with lower urinary tract symptoms suggestive of benign prostatic hyperplasia was systematically evaluated with multi-channel computer-urodynamic investigation and IVU. Men with urinary retention, known bladder stones or diverticula, severely impaired renal function, or allergy to iodine contrast media were excluded. Structural alterations of the urinary tract were correlated with clinical and urodynamic data using logistic regression analysis. RESULTS: Data on 203 consecutive patients were available for analysis. Multivariate analysis demonstrated that the "fish-hook" configuration of the distal ureter (also known as "hockey-stick", or "J-shaped" ureter) was the only sign significantly associated with benign prostatic obstruction (BPO) (odds-ratio 3.64; 95% confidence interval 1.69-7.83; P < 0.001). The sensitivity, specificity, positive and negative predictive values of the "fish-hook" ureter configuration sign to detect BPO was 53, 76, 61 and 70%, respectively. Bladder trabeculation, upper urinary tract dilatation, or bladder base elevation were not associated with BPO, detrusor overactivity, detrusor underactivity, bladder low-compliance or any clinical data. CONCLUSIONS: The "fish-hook" shape of the distal ureter(s) indicates BPO and may be a result of prostate median lobe enlargement.

Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample.

PURPOSE: The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters. METHODS: A random sample of the population-based Herne lower urinary tract symptoms cohort was analysed. All these men underwent a detailed urological work-up. Two polymorphisms in the CYP19A1 gene [rs700518 in exon 4 (A57G); rs10046 at the 3'UTR(C268T)] and one in the 3'UTR of CYP3A4 [rs2740574 (A392G)] were determined by TaqMan assay from genomic DNA of peripheral blood. These polymorphisms were correlated to clinical and laboratory BPH-parameters. RESULTS: A total of 392 men (65.4 ± 7.0 years; 52-79 years) were analysed. Mean International Prostate Symptom Score (IPSS; 7.5), Q (max) (15.4 ml/s), prostate volume (31 ml) and prostate specific antigen (PSA) (1.8 ng/ml) indicated a typical elderly population. Both polymorphisms in the CYP19A1 gene were not correlated to age, IPSS, Q (max), prostate volume and post-void residual volume. Serum PSA was higher in men carrying the heterozygous rs10046 genotype (2.0 ± 0.1 ng/ml) than in those with the CC-genotype (1.7 ± 0.2 ng/ml, P = 0.012). Men carrying one a mutated allele of the CYP3A4 gene had smaller prostates (27.0 ± 2.0 vs. 32 ± 0.8 ml, P = 0.02) and lower PSA levels (1.6 ± 0.3 vs. 1.9 ± 0.1 ng/ml). CONCLUSIONS: The inconsistent associations observed herein and for other gene polymorphisms warrant further studies. In general, the data regarding the association of gene polymorphism to BPH-parameters suggest that this disease is caused by multiple rather than a single genetic variant. A rigorous patient selection based on anatomo-pathological and hormonal profile may possible reduce the number of confounders for future studies thus enabling a more detailed assessment of the association between genetic factors and BPH-parameters.

[Prostate Carcinoma Mimics Lung Carcinoma: A Case Report]. / Prostatakarzinom imitiert metastasiertes Bronchialkarzinom ­ Ein Fallbericht.

A PSA-negative, advanced adenocarcinoma of the prostate is a rare finding. Expression of thyroid transcription factor-1 (TTF-1) in the tumour in combination with a previous medical history of lung adenocarcinoma could complicate the final diagnosis. To the best of our knowledge, we present the second case of a TTF-1-positive, acinar adenocarcinoma of the prostate.We present the case of a 65-year-old male with surgically treated lung adenocarcinoma; 3 years later we diagnosed adenocarcinoma of the bladder and prostate. Although our initial assumption was that the patient had metastatic lung carcinoma in the bladder and prostate, a further immune histochemical analysis of the carcinoma with Napsin A, CK7 and CK20, along with the evaluation of the clinical manifestations, led us to the diagnosis of primary adenocarcinoma of the prostate.

Alfuzosin: a clinically uroselective α1-blocker.

A once-daily (o.d.) formulation of alfuzosin has recently been developed in order to improve the convenience of dosing and to provide optimal pharmacokinetic coverage over a 24-h period. The results of two double-blind, placebo-controlled phase III studies of similar design that included 983 patients with LUTS that suggested BPH have confirmed that alfuzosin 10 mg o.d. is a 24-h effective treatment for both symptoms and flow rates, and that there is no additional benefit in using a higher dosage. In addition, alfuzosin is the only α1-blocker that has demonstrated a significant decrease in post-void residual urine, a known risk factor for acute urinary retention, as well as the incidence of acute urinary retention in comparison with a placebo. Administered without an initial dose titration, alfuzosin 10 mg o.d. is well tolerated, with a low incidence of postural hypotension (<1%) and no significant changes in blood pressure compared with a placebo, even in elderly and hypertensive patients. Ejaculation disorders were rarely reported and did not show an evident causal relationship to treatment. Alfuzosin 10 mg o.d. also exhibits an excellent sexual side-effect profile, with no deleterious impact on this important aspect of quality of life for BPH patients.

Age and bladder outlet obstruction are independently associated with detrusor overactivity in patients with benign prostatic hyperplasia.

BACKGROUND: Detrusor overactivity is one known cause of lower urinary tract symptoms and has been linked to bladder storage symptoms (urgency, frequency, or urge incontinence). OBJECTIVE: To determine clinical and urodynamic parameters associated with detrusor overactivity in patients with suspected benign prostatic hyperplasia. DESIGN, SETTING, AND PARTICIPANTS: During 1993-2003, urodynamic investigations were performed in patients aged 40 yr or older and with lower urinary tract symptoms, benign prostatic enlargement, and/or suspicion of bladder outlet obstruction (maximum flow rate < 15 ml/s or postvoid residual urine > 50 ml). MEASUREMENTS: Detrusor overactivity was defined according to the new International Continence Society classification (2002) as involuntary detrusor contractions during cystometry, which may be spontaneous or provoked, regardless of amplitude. The Schäfer algorithm was used to determine bladder outlet obstruction. RESULTS: In total, 1418 men were investigated (median age: 63 yr) of whom 864 men (60.9%) had detrusor overactivity. In univariate analysis, men with detrusor overactivity were significantly older, more obstructed, had larger prostates, higher irritative International Prostate Symptoms Score subscores, a lower voiding volume at free uroflowmetry, and a lower bladder capacity at cystometry. The prevalence of detrusor overactivity rose continuously with increasing bladder outlet obstruction grade. Multivariate analysis showed that only age and bladder outlet obstruction grade were independently associated with detrusor overactivity. After age adjustment, the odds ratios of detrusor overactivity compared to Schäfer class 0 were 1.2 for class I, 1.4 for class II, 1.9 for class III, 2.5 for class IV, 3.4 for class V, and 4.7 for class VI. CONCLUSIONS: In patients with clinical benign prostatic hyperplasia, detrusor overactivity is independently associated with age and bladder outlet obstruction. The probability of detrusor overactivity rises with increasing age and bladder outlet obstruction grade.

Diagnostic accuracy of noninvasive tests to evaluate bladder outlet obstruction in men: detrusor wall thickness, uroflowmetry, postvoid residual urine, and prostate volume.

OBJECTIVES: The aim of this prospective study was to compare the diagnostic accuracy of detrusor wall thickness (DWT), free uroflowmetry, postvoid residual urine, and prostate volume (index tests) with pressure-flow studies (reference standard) to detect bladder outlet obstruction (BOO) in men. METHODS: During a 2-yr period, men older than 40 yr with lower urinary tract symptoms and/or prostatic enlargement had the following tests: ultrasound measurements of DWT, free uroflowmetry (Q(max), Q(ave)), postvoid residual urine, and prostate volume. Pressure-flow studies were used to divide obstructed from nonobstructed bladders. RESULTS: One hundred sixty men between 40-89 yr of age (median: 62 yr) were included in the study; 75 patients (46.9%) had BOO according to pressure-flow studies. The results of all investigated index tests differed significantly between obstructed and nonobstructed men. DWT was the most accurate test to determine BOO: the positive predictive value was 94%, specificity 95%, and the area under the curve of ROC analysis 0.93. There was an agreement of 89% between the results of DWT measurement and pressure-flow studies. CONCLUSIONS: Measurements of DWT can detect BOO better than free uroflowmetry, postvoid residual urine, or prostate volume. In clinical routine, DWT measurements can be used to judge BOO noninvasively.

Long-term therapy with the dual 5alpha-reductase inhibitor dutasteride is well tolerated in men with symptomatic benign prostatic hyperplasia.

OBJECTIVE: To examine the long-term (4-year) safety and tolerability of dutasteride in the treatment of symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients who completed the double-blind phase of three dutasteride Phase III studies were eligible to enter a 2-year open-label extension, during which all patients received dutasteride 0.5 mg. Safety was assessed, including adverse-event reporting, clinical laboratory assessments, yearly physical examinations, and vital sign assessments. RESULTS: In all, 2340 patients entered the open-label phase, 1188 of whom previously received dutasteride during the double-blind phase of the study. The most common drug-related adverse events (occurring in > or = 1%) were effects on sexual function, which decreased with a longer duration of therapy. Gynaecomastia was reported in a small percentage of men throughout the 4-year study period. The incidence of individual sexual functional adverse events that led to withdrawal was < or = 1% (0.3-1.0%) during the 4-year study period. Dutasteride had no relevant effects on vital signs or clinical laboratory variables. CONCLUSION: These data show that dutasteride is well tolerated during long-term use for the treatment of symptomatic BPH.

Ultrasound measurement of detrusor wall thickness in healthy adults.

AIMS: Measurements of detrusor wall thickness (DWT) are used to diagnose bladder outlet obstruction (BOO). No values of DWT exist in healthy adults so far. These values, however, are necessary to judge DWT in patients with suspected BOO correctly. The aim of this study was to determine DWT in healthy adults and to investigate if bladder filling, gender, age, or body-mass index (BMI) influences DWT. MATERIALS AND METHODS: In 55 healthy adult volunteers between 15 and 40 years of age, DWT was measured at the anterior bladder wall with a 7.5 MHz ultrasound probe and with a full bladder. In nine of those volunteers, an urodynamic investigation was performed additionally during which DWT was measured in steps of 50 ml until 300 ml and in steps of 100 ml until the maximum bladder volume. RESULTS: DWT decreases rapidly during the first 250 ml of bladder filling but, thereafter, remains almost stable until maximal bladder capacity. No statistical difference was found between DWT at 250 ml and DWT at a higher bladder filling. Men had a greater DWT compared to women (1.4 vs. 1.2 mm, P < 0.001). The age and BMI did not have a significant impact on DWT. CONCLUSIONS: DWT remains stable at a bladder filling of 250 ml. At this state of bladder filling, DWT between different groups are comparable. Men have to be evaluated separately from women.

Alfuzosin: a clinically uroselective alpha1-blocker.

A once-daily (o.d.) formulation of alfuzosin has recently been developed in order to improve the convenience of dosing and to provide optimal pharmacokinetic coverage over a 24-h period. The results of two double-blind, placebo-controlled phase III studies of similar design that included 983 patients with LUTS that suggested BPH have confirmed that alfuzosin 10 mg o.d. is a 24-h effective treatment for both symptoms and flow rates, and that there is no additional benefit in using a higher dosage. In addition, alfuzosin is the only alpha1-blocker that has demonstrated a significant decrease in post-void residual urine, a known risk factor for acute urinary retention, as well as the incidence of acute urinary retention in comparison with a placebo. Administered without an initial dose titration, alfuzosin 10 mg o.d. is well tolerated, with a low incidence of postural hypotension (< 1%) and no significant changes in blood pressure compared with a placebo, even in elderly and hypertensive patients. Ejaculation disorders were rarely reported and did not show an evident causal relationship to treatment. Alfuzosin 10 mg o.d. also exhibits an excellent sexual side-effect profile, with no deleterious impact on this important aspect of quality of life for BPH patients.

Increase in detrusor wall thickness indicates bladder outlet obstruction (BOO) in men.

Detrusor wall thickness decreases continuously while the bladder fills to 50% of its capacity and then remains constant until 100%. Therefore, detrusor wall measurements were performed in patients when the bladder was filled to maximum capacity only. Mean detrusor wall thickness for unobstructed (n = 14), equivocal (n=23) and obstructed patients (n=33) were 1.33, 1.62 and 2.4 mm, respectively (P <0.001). With increasing CHESS letters and CHESS numbers, the thickness of the detrusor wall increased as well (P< 0.001). The positive predictive value of detrusor wall measurement (95.5% for a cut-off value greater than or equal to 2 mm) was superior to all other predictors investigated. The thickness of the detrusor wall increases depending on the extent of BOO. Both constrictive and compressive BOO lead to an increase in detrusor wall thickness. BOO is found in 95.5% of men with a detrusor wall thickness greater than or equal to 2 mm. Measuring the thickness of the detrusor wall can be used as a screening test to detect BOO.

Sacral electrical neuromodulation as an alternative treatment option for lower urinary tract dysfunction.

Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives.