Objectives: To evaluate the impact of prostate size on functional outcomes and perioperative morbidity, we analyzed patients undergoing holmium laser enucleation of the prostate (HoLEP) for lower urinary tract symptoms (LUTS). As LUTS secondary to benign prostatic obstruction (BPO) are a chronic progressive disease, prevalence and prostate size increase with age. HoLEP is a size‐independent method for surgical treatment of LUTS/BPO and can be offered in medication‐refractory patients with durable long‐term results and reduced perioperative morbidity.Methods: We retrospectively collected data of 852 patients who underwent HoLEP for LUTS secondary to BPO between 2014‐2018. Patients were divided into group 1 (≤60 cc), group 2 (>60 < 120 cc), group 3 (≥120 cc). Perioperative parameters, safety and short‐term functional outcomes were assessed and analyzed.Results: Patients in group 3 were significantly older and showed a significantly higher median prostate‐specific antigen level. Perioperative parameters, such as enucleation time and morcellation time significantly differed in favor of smaller prostate sizes, while enucleation and morcellation speed showed favorable results for larger prostate sizes. Larger prostates ≥120 cc showed a significantly higher postoperative drop in hemoglobin. However, patients did not differ in postoperative functional outcomes or Clavien‐Dindo grade ≥II complications (4.8% of all patients [41/852]). There was no difference in perioperative complications between all groups (P = 0.760).Conclusion: While larger prostates take significantly longer to operate on, postoperative functional outcomes show no difference between all sizes. In conclusion, HoLEP is a size‐independent and effective method for surgical treatment of LUTS/BPO in prostates ≥30 cc.

Objectives: With holmium laser enucleation of the prostate (HoLEP) a size‐independent method for surgical treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) has been introduced. HoLEP offers durable long‐term results with reduced perioperative morbidity. As the risk of disease progression increases with age, the main goals, when offering surgery to an elderly population, are reducing perioperative morbidity and preserving quality of life (QoL). We therefore analyzed the impact of age on outcomes and perioperative morbidity in patients undergoing HoLEP for LUTS at our tertiary referral center.Methods: We retrospectively collected data of 487 patients who underwent HoLEP for LUTS secondary to BPO between 2018 and 2019. Patients were divided into group 1 (<70 years), group 2 (70‐79 years), and group 3 (≥80 years). Perioperative parameters, safety, and short‐term functional outcomes were assessed and analyzed.Results: Perioperative Clavien‐Dindo grade ≥II complications were seen in 4.1% of patients (20/487). There was no difference in perioperative complications between all age groups (P = .176). Functional outcome was assessed 30 days post surgery. There was significant improvement in median International Prostate Symptom Score of 14, 10, and 8 points for groups 1, 2, and 3 (P < .001), respectively, with constant improvement of median QoL of 3 points for all groups. Median maximum flow rate (Q_max) showed significant improvement of 14.5, 10.5, and 13 mL/s for groups 1 to 3 (P = .467), respectively.Conclusion: HoLEP offers acceptable perioperative complication rates even in the oldest patient cohort (≥80 years). Therefore, HoLEP is a safe and efficient option even in oldest patients.

Prostate smooth muscle tone and hyperplastic growth are involved in the pathophysiology and treatment of male lower urinary tract symptoms (LUTS). Available drugs are characterized by limited efficacy. Patients’ adherence is particularly low to combination therapies of 5α-reductase inhibitors and α₁-adrenoceptor antagonists, which are supposed to target contraction and growth simultaneously. Consequently, molecular etiology of benign prostatic hyperplasia (BPH) and new compounds interfering with smooth muscle contraction or growth in the prostate are of high interest. Here, we studied effects of p21-activated kinase (PAK) inhibitors (FRAX486, IPA3) in hyperplastic human prostate tissues, and in stromal cells (WPMY-1). In hyperplastic prostate tissues, PAK1, -2, -4, and -6 may be constitutively expressed in catecholaminergic neurons, while PAK1 was detected in smooth muscle and WPMY-1 cells. Neurogenic contractions of prostate strips by electric field stimulation were significantly inhibited by high concentrations of FRAX486 (30 μM) or IPA3 (300 μM), while noradrenaline- and phenylephrine-induced contractions were not affected. FRAX486 (30 μM) inhibited endothelin-1- and -2-induced contractions. In WPMY-1 cells, FRAX486 or IPA3 (24 h) induced concentration-dependent (1–10 μM) degeneration of actin filaments. This was paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486 or IPA3. Cytotoxicity of FRAX486 and IPA3 in WPMY-1 cells was time- and concentration-dependent. Stimulation of WPMY-1 cells with endothelin-1 or dihydrotestosterone, but not noradrenaline induced PAK phosphorylation, indicating PAK activation by endothelin-1. Thus, PAK inhibitors may inhibit neurogenic and endothelin-induced smooth muscle contractions in the hyperplastic human prostate, and growth of stromal cells. Targeting prostate smooth muscle contraction and stromal growth at once by a single compound is principally possible, at least under experimental conditions.

Voiding symptoms in benign prostatic hyperplasia (BPH) are driven by prostate smooth muscle contraction and prostate growth. Smooth muscle contraction in the prostate and other organs critically depends on activation of the small monomeric GTPase RhoA and probably Rac1. A role of another GTPase, ADP-ribosylation factor 6 (ARF6), for smooth muscle contraction has been recently suggested by indirect evidence but remains to be proven for any organ. Here, we report effects of NAV2729, an inhibitor with assumed specificity for ARF6, in human prostate tissues and cultured prostate stromal cells (WPMY-1). NAV2729 (5 μm) inhibited neurogenic and α₁-adrenergic contractions of human prostate tissues. Contractions induced by endothelin-1, by the thromboxane A₂ agonist U46619, or by high molar KCl were not inhibited. Correlation analyses suggested up-regulation of prostatic ARF6 expression with increasing degree of BPH, as ARF6 expression increased with the content of prostate-specific antigen (PSA) of prostate tissues. NAV2729 inhibited ARF6 activity but not other GTPases (ARF1, RhoA, Rac1) in prostate tissues and in WPMY-1 cells. Proliferation of WPMY-1 cells was inhibited concentration-dependently by NAV2726, as reflected by decreased viability, 5-ethynyl-2′-deoxyuridine (EdU) assay, colony formation assay, and expression of Ki-67. Silencing of ARF6 expression mimicked effects of NAV2729 on viability and in the EdU assay. Effects of NAV2729 on viability and proliferation were attenuated in cells with silenced ARF6 expression. Our findings suggest that a NAV2729-sensitive mechanism promotes adrenergic contraction and stromal cell growth in the human prostate, which is probably ARF6-mediated. Similar actions in other organs and urodynamic effects of NAV2729 appear possible.