Effect of preoperative detrusor underactivity on long-term surgical outcomes of photovaporization and holmium laser enucleation in men with benign prostatic hyperplasia: a lesson from 5-year serial follow-up data.

OBJECTIVES: To investigate the impact of preoperative detrusor underactivity (DU) on serial treatment outcomes over the course of 5 years after photovaporization (PV) or holmium laser enucleation (HoLEP) in patients with benign prostatic hyperplasia (BPH), to compare its impact after PV vs HoLEP, and to identify predictors of long-term lower urinary tract symptoms (LUTS) improvement. MATERIALS AND METHODS: This study involved 245 patients with BPH who had complete 5-year follow-up data (PV using 120W-HPS, n = 143, HoLEP, n = 102), grouped as follows: PV-HPS-DU(+), n = 114; PV-HPS-DU(-), n = 29; HoLEP-DU(+), n = 56; and HoLEP-DU(-), n = 46. Bladder contractility index (BCI) < 100 was regarded as DU. Serial treatment outcomes for the International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry and serum PSA level at 6 months, and at 1, 2, 3, 4 and 5 years after surgery, were compared among the groups. LUTS improvement was defined as a reduction in total IPSS of ≥50% relative to baseline. RESULTS: Improvement in total IPSS, quality of life (QoL) index and post-void residual urine volume (PVR) in the PV-HPS-DU(+) and PV-HPS-DU(-) groups were maintained up to 5 years after PV, except for maximum urinary flow rate (Qmax ) and bladder voiding efficiency. In the HoLEP-DU(+) and HoLEP-DU(-) groups, improvements in all outcome variables were maintained up to 5 years after HoLEP. Deteriorations in subtotal voiding symptom score, total IPSS and Qmax with time during the long-term period after surgery were more pronounced in the PV-HPS-DU(+) and HoLEP-DU(+) groups than in the PV-HPS-DU(-) and HoLEP-DU(-) groups. Reductions in subtotal voiding symptom score, total IPSS, QoL index, and serum PSA were greater in the HoLEP-DU(+) group than in the PV-HPS-DU(+) group throughout follow-up. The type of surgery (HoLEP vs PV) and higher baseline BCI were independent predictors of LUTS improvement at 5 years after surgery. CONCLUSION: Generally, improvement of micturition symptoms, QoL and PVR in patients with DU appears to be maintained up to 5 years after PV or HoLEP. Deterioration of voiding symptoms and urinary flow rate at long-term follow-up visits after PV or HoLEP was more pronounced in patients with LUTS/BPH with DU than in those without DU. Patients with BPH with DU may benefit from more complete removal of prostatic adenoma by HoLEP and greater baseline bladder contractility in terms of micturition symptoms and QoL.

Long-Term Outcomes of Laser Prostatectomy for Storage Symptoms: Comparison of Serial 5-Year Followup Data between High Performance System Photoselective Vaporization and Holmium Laser Enucleation of the Prostate.

PURPOSE: We compared long-term storage symptom outcomes between photoselective laser vaporization of the prostate with a 120 W high performance system and holmium laser enucleation of the prostate. We also determined factors influencing postoperative improvement of storage symptoms in the long term. MATERIALS AND METHODS: Included in our study were 266 men, including 165 treated with prostate photoselective laser vaporization using a 120 W high performance system and 101 treated with holmium laser enucleation of the prostate, on whom 60-month followup data were available. Outcomes were assessed serially 6, 12, 24, 36, 48 and 60 months postoperatively using the International Prostate Symptom Score, uroflowmetry and the serum prostate specific antigen level. Postoperative improvement in storage symptoms was defined as a 50% or greater reduction in the subtotal storage symptom score at each followup visit after surgery compared to baseline. RESULTS: Improvements in frequency, urgency, nocturia, subtotal storage symptom scores and the quality of life index were maintained up to 60 months after photoselective laser vaporization or holmium laser enucleation of the prostate. There was no difference in the degree of improvement in storage symptoms or the percent of patients with postoperative improvement in storage symptoms between the 2 groups throughout the long-term followup. However, the holmium laser group showed greater improvement in voiding symptoms and quality of life than the laser vaporization group. On logistic regression analysis a higher baseline subtotal storage symptom score and a higher BOOI (Bladder Outlet Obstruction Index) were the factors influencing the improvement in storage symptoms 5 years after prostate photoselective laser vaporization or holmium laser enucleation. CONCLUSIONS: Our serial followup data suggest that storage symptom improvement was maintained throughout the long-term postoperative period for prostate photoselective laser vaporization with a 120 W high performance system and holmium laser enucleation without any difference between the 2 surgeries. Also, more severe storage symptoms at baseline and a more severe BOOI predicted improved storage symptoms in the long term after each surgery.

Can preoperative detrusor underactivity influence surgical outcomes of 120 W HPS vaporization of the prostate (PVP) or holmium laser enucleation of the prostate (HoLEP)? A serial 3-year follow-up study.

AIMS: To determine the influence of preoperative detrusor underactivity (DU) on serial long-term outcomes of HPS/PVP or HoLEP for LUTS/BPH, and to compare the influence between the two surgeries. METHODS: A total of 382 men, who underwent 120W-HPS/PVP or HoLEP for LUTS/BPH and for whom 36-month follow-up data were available, were classified into four groups: HPS with DU (n = 145), HPS without DU (n = 44), HoLEP with DU (n = 105), and HoLEP without DU (n = 88). DU was defined as bladder contractility index of <100. Surgical outcomes were assessed at postoperative 6, 12, 24, and 36 months using IPSS, uroflowmetry, and serum PSA. RESULTS: All four groups maintained improvements in voiding symptom score (VSS), storage symptom score, total-IPSS, QOL index, maximum flow rate (Qmax), post-void residual urine volume (PVR), and bladder voiding efficiency (BVE) compared with baseline up to 3 years postoperatively. There were no significant differences in improvements of postoperative IPSS parameters including QOL index between men with and without DU throughout the follow-up period after HPS or HoLEP. In men with DU, there were no significant differences in improvements of postoperative QOL index, Qmax, PVR, or BVE between HPS and HoLEP groups throughout the follow-up period, except for VSS and total IPSS. Serum PSA reductions after HoLEP were greater than after PVP. CONCLUSIONS: Improvements in LUTS, Qmax, and BVE can maintain up to 3 years after HPS or HoLEP for LUTS/BPH, irrespective of the presence or absence of preoperative DU. Although HoLEP may provide more durable improvement of VS in men with DU than HPS, there seems to be no difference in improvement of QOL or Qmax or BVE between HPS and HoLEP.

A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Therapeutic Confirmatory Study to Evaluate the Safety and Efficacy of Avanafil in Korean Patients with Erectile Dysfunction.

A multi-center, randomized, double-blind, placebo-controlled study was conducted with 158 subjects who were randomized to placebo or avanafil 50, 100, and 200 mg on demand for 8 weeks to evaluate the safety, tolerability, and efficacy of avanafil in the treatment of erectile dysfunction (ED) in Korean men. The primary outcome was the erectile function (EF) domain score of the International Index of Erectile Function (IIEF) questionnaire. Secondary outcomes included changes in the scores of IIEF questions 3 and 4 (IIEF Q3, Q4) from baseline, changes in all domain scores in the IIEF from baseline, Sexual Encounter Profile questions 2-5 (SEP2-5), the Global Efficacy Assessment Question (GEAQ), and the number of subjects whose EF domain score at the 8th week visit was ≥ 26. After 8 weeks of treatment, the dose groups except avanafil 50 mg scored significantly higher on the IIEF-EF domain from baseline than the placebo group. The changes from baseline in the avanafil group in IIEF Q3 (all doses) and Q4 (200 mg alone) were higher than the placebo group. The differences between avanafil and placebo groups were significant in SEP2 (100 and 200 mg) and SEP3-5 (200 mg). The differences in the GEAQ "Yes" response were also significant in the avanafil 100 and 200 mg groups. Regarding the ratio of normal EF at the end of the study, avanafil 200 mg differed significantly from the placebo. Most treatment-associated adverse events were mild and resolved spontaneously. This is a clinical trial study and was registered at www.ClinicalTrials.gov (Identifier: NCT02477436).

A Phase 3 Study to Evaluate the 1-Year Efficacy and Safety of Udenafil 75 mg Once Daily in Patients With Erectile Dysfunction.

INTRODUCTION: Once-daily administration of phosphodiesterase type 5 inhibitors has been shown to correct erectile dysfunction (ED). AIM: To evaluate the long-term efficacy and safety after once-daily oral administration of udenafil 75 mg in men with ED. METHODS: This clinical trial was an open-label, fixed-dose, 24-week extension study (DA8159_EDDL_III) of a 24-week double-blinded efficacy and safety study of once-daily udenafil (parent study: DA8159_EDD_III). Subjects received udenafil 75 mg once daily for 24 weeks during this extension study, and the follow-up visit occurred during the 4-week ED treatment-free period. MAIN OUTCOME MEASURES: Subjects were asked to complete the International Index of Erectile Function questionnaire and the Global Assessment Questionnaire at the 24-week extension and after the 4-week ED treatment-free period, and the development of adverse drug reactions was investigated. RESULTS: In total, 302 subjects were enrolled in this extension study. Improvement was shown with an increased erectile function (EF) domain score compared with baseline (14.60 ± 4.57) at extension week 48 (23.98 ± 5.44) and a slight increase in EF domain score compared with the last time point (week 24) of the parent study (P < .001). The Global Assessment Questionnaire showed a high improvement rate of 95.4% at the extension 48-week time point. For shift to normal, almost half the subjects (45.1%) recovered "normal" EF, and 14.2% of subjects reported normal erections after the 4-week ED treatment-free period. The occurrence rate of adverse drug reactions was 8%, which consisted mainly of flushing and headache. CONCLUSION: Once-daily dosing of udenafil 75 mg showed excellent efficacy and safety with long-term administration and allowed a more spontaneous sexual life.

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

OBJECTIVES: To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. METHODS: We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. RESULTS: Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 µg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). CONCLUSIONS: Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume.

Restoration of erectile function by suppression of corporal apoptosis, fibrosis and corporal veno-occlusive dysfunction with rho-kinase inhibitors in a rat model of cavernous nerve injury.

PURPOSE: We determined whether Rho-kinase inhibition would improve corporal veno-occlusive dysfunction by suppressing apoptosis and fibrosis via normalization of the Rho-kinase driven pathways related to the 2 structural alterations in a rat model of cavernous nerve crush injury. MATERIALS AND METHODS: A total of 30 male 10-week-old male Sprague Dawley® rats were equally divided into 3 groups, including sham surgery, cavernous nerve crush injury and cavernous nerve crush injury treated with fasudil. The treated group received fasudil (30 mg/kg) daily for 4 weeks starting day 1 postoperatively. Electrostimulation and dynamic infusion cavernosometry were performed 4 weeks postoperatively. Penile tissue was processed for imm unohistochemistry, double immunofluorescent and Masson trichrome staining, TUNEL, caspase-3 activity assay and Western blot. RESULTS: The cavernous nerve crush injury group showed significantly lower intracavernous pressure/mean arterial pressure, and higher maintenance and drop rates than the sham surgery group. Rho-kinase inhibition in the injury plus fasudil group restored erectile responses and dynamic infusion cavernosometry parameters. Increased apoptosis, decreased immunohistochemical staining of α-SMA and increased caspase-3 activity were noted in the injury group. In that group densitometry revealed increased ROCK1 expression, increased MYPT1 phosphorylation, decreased Akt phosphorylation, decreased Bad phosphorylation and a decreased Bcl2-to-Bax ratio. A significantly decreased smooth muscle-to-collagen ratio and increased fibroblast pCofilin were also observed in the injury group, as was increased phosphorylation of cofilin, a downstream effector of LIMK2. Rho-kinase inhibition in the injury plus fasudil group alleviated the histological and molecular dysregulation. CONCLUSIONS: Our data suggest that early inhibition of Rho-kinase after cavernous nerve crush injury may prevent corporal apoptosis and fibrosis by suppressing the Akt/Bad/Bax/caspase-3 and LIMK2/cofilin pathways, preventing corporal veno-occlusive dysfunction and erectile dysfunction.

Effect of chronic administration of PDE5 combined with glycemic control on erectile function in streptozotocin-induced diabetic rats.

INTRODUCTION: Chronic treatment with phosphodiesterase type 5 inhibitors (PDE5) is effective in an animal model of diabetes-induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED. AIMS: We evaluated the effect of chronic administration of PDE5 combined with glycemic control on DMED. METHODS: Sprague-Dawley rats (8 weeks old) were divided into five groups (n = 10 each): normal control (C), diabetes (DM), DM treated with insulin (DM-I), DM treated with PDE5 (DM-P), and DM treated with insulin and PDE5 (DM-I + P). Rats in the diabetic groups received an injection of streptozotocin (45 mg/kg). After 10 weeks of induced diabetes, the DM-I group was treated with a daily injection of neutral protamine Hagedorn, and the DM-P group was treated with a daily dosage of 20 mg/kg PDE5 (DA-8159) for 4 weeks. The DM-I + P group was treated with both treatments simultaneously. After 14 weeks of induced diabetes, an evaluation of erectile function and histological and biochemical markers of corporal tissue was performed. MAIN OUTCOME MEASURES: Erectile function and histological and biochemical markers in corporal tissue. RESULTS: Rats in the DM group showed markedly lower erectile parameters than those in the C group, whereas rats in the DM-I and DM-P groups showed intermediate erectile function between the DM and C groups. Rats in the DM-I + P group showed restored erectile function, comparable with group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of endothelial nitric oxide synthase and Akt displayed a similar pattern with the results from cavernosometry (DM < DM-I = DM-P < DM-I + P = C, P < 0.05). The distribution of phosphorylated myosin phosphatase target subunit 1 was in the reverse order. CONCLUSIONS: Chronic administration of PDE5 or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5.

Involvement of Rho-Kinase/LIM Kinase/Cofilin Signaling Pathway in Corporal Fibrosis after Cavernous Nerve Injury in Male Rats.

INTRODUCTION: The molecular mechanism of corporal fibrosis leading to erectile dysfunction (ED) following cavernous nerve (CN) injury is poorly understood. AIM: To determine whether the LIMK2/cofilin pathway, the downstream effectors of ROCK1, was involved in ED and corporal fibrosis following bilateral CN injury in male rats. METHODS: Forty-eight 10-week-old male Sprague-Dawley rats were equally divided into three groups: sham surgery (S); bilateral CN crush injury (I); and bilateral CN resection (R). Within each groups, two subgroups were analyzed at 1 and 4 weeks postoperatively. MAIN OUTCOME MEASURES: Electrostimulation was performed to assess erectile function by the ratio of maximal intracavernous pressure to mean arterial pressure (ICP/MAP) and areas under the ICP curve to MAP (AUC/MAP). Penile tissue was processed for Masson's trichrome staining, Western blot (ROCK1, total LIMK2, phospho-LIMK2, total cofilin, phospho-cofilin), immunohistochemistry (alpha-SM actin [α-SMA]), and double immunofluorescent staining (ROCK1, phospho-LIMK2, vimentin). RESULTS: At each time point, both I and R groups showed a significantly lower percent of ICP/MAP and AUC, and decreased SM cell/collagen ratio and expression of α-SMA than S group. Densitometry revealed a significantly higher expression of ROCK1 in I and R groups compared with S group at all time points. The LIMK2 phosphorylation in I and R groups significantly increased at 1 week, but not at 4 weeks. The cofilin phosphorylation in R group significantly increased to that in S group starting at 1 week, while that in I group was increased significantly at 4 weeks. The double immunofluorescent staining noted that coexpression of vimentin with ROCK1 or phospho-LIMK2 in I and R groups was significantly increased mainly in the subtunical area at 1 week but not at 4 weeks. CONCLUSIONS: The ROCK1/LIMK2/cofilin pathway may be involved in ED related to corporal fibrosis, and it appears to be functional particularly in the early period after CN injury.

Efficacy of once-daily administration of udenafil for 24 weeks on erectile dysfunction: results from a randomized multicenter placebo-controlled clinical trial.

INTRODUCTION: The method of administration of oral phosphodiesterase-5 inhibitors has been expanded to once-daily repeated administration with lower initial dosage than on-demand administration. AIM: The aim of this study was to evaluate the efficacy and safety of once-daily udenafil as a treatment for erectile dysfunction (ED) for intermediate-term period. METHODS: This multicenter, randomized, double-blind clinical trial included 346 ED patients (placebo, udenafil 50 mg, udenafil 75 mg). Subjects were treated with each medication once daily for 24 weeks. MAIN OUTCOME MEASURES: Subjects were asked to complete the International Index of Erectile Function (IIEF)-erectile function (EF) domain at baseline, 12 weeks, and 24 weeks and the development of adverse drug reactions (ADRs) was inspected. RESULTS: Both dosages of udenafil induced a significant increase in IIEF-EF compared with placebo at both 12 and 24 weeks. When patients were divided according to the severity of baseline EF score, significant improvement was observed only with udenafil 75 mg regardless of the degree of ED. At 24 weeks, the proportions of patients who reported a return to normal EF (IIEF-EF over 26) were 39.1% for udenafil 50 mg and 47.0% for udenafil 75 mg. In terms of safety, ADRs were observed in 6.1%, 12.9%, and 17.9% for placebo, udenafil 50 mg, and 75 mg, respectively. Although a statistically higher rate of ADRs was observed in the udenafil 75 mg group (P = 0.024), the majority were mild and recovered without treatment. CONCLUSIONS: Once-daily administration of udenafil 50 mg and 75 mg for 24 weeks resulted in improvement of EF. In particular, udenafil 75 mg improves EF regardless of the baseline degree of ED.

Change in storage symptoms following laser prostatectomy: comparison between photoselective vaporization of the prostate (PVP) and holmium laser enucleation of the prostate (HoLEP).

PURPOSE: To compare serial changes of postoperative storage symptoms between PVP and HoLEP, and to identify the predictors influencing postoperative improvement of storage symptoms. METHODS: A total of 486 men (PVP group: 213 cases; HoLEP group: 273 cases), in whom 12-month follow-up data were available, were included in this retrospective study. Surgical outcomes were evaluated at 1-, 3-, 6-, and 12 months postoperatively using the IPSS, uroflowmetry with post-void residual urine volume (PVR) and serum PSA levels. Improvement of storage symptoms was defined as a reduction by ≥50 % of the subtotal storage symptom score postoperatively compared to baseline. RESULTS: In both PVP and HoLEP groups, total IPSS, quality-of-life index, frequency score, nocturia score, maximum flow rate and PVR were significantly decreased compared to baseline starting from 1 month after surgery. Whereas urgency score was numerically increased compared to baseline at 1 month after PVP, it was reduced compared to baseline at 1 month after HoLEP. While the subtotal storage symptom score was significantly decreased compared to baseline starting from 3 months after PVP, it was significantly reduced starting from 1 month after HoLEP. On logistic regression analysis, a higher baseline subtotal storage symptom score was the only independent predictor of improvement in storage symptoms after PVP or HoLEP. CONCLUSIONS: Our data suggest that improvement in storage symptoms after HoLEP begins earlier than that after PVP. Also, this study indicates that patients with more severe baseline storage symptoms have a higher likelihood of improvement after PVP or HoLEP compared to those with less severe symptoms.

Should men with mild erectile dysfunction be closely evaluated for cardiovascular diseases in the Korean population?

This study compared demographic characteristics and prevalence of cardiovascular comorbidities between men with mild erectile dysfunction (ED) and men with more severe ED. Men with 6-month history of ED and in monogamous heterosexual relationships were included. Non-responders to type 5 phosphodiesterase inhibitors or patients receiving regular treatment with nitrate, anticoagulants, androgens, and anti-androgens were excluded. ED was defined according to the International Index of Erectile Function questionnaire score: no ED (≥26), mild ED (22-25), and others (<22). The review identified 70 patients with mild ED (6.0%, group A) and 1098 patients with more severe ED (94.0%, group B) were included. Of the patients in group B, 365 had mild-to-moderate ED (30.5%), 505 had moderate ED (43.2%), and 233 had severe ED (20.0%). Mean ages and body mass indices showed no differences between groups A and B. Group A had shorter mean duration of ED (p = 0.025). Although patients in group A had milder ED with shorter duration than group B patients, cardiovascular risk factors such as diabetes, hypertension and lipid disorder were still common for group A. The most common comorbidity was diabetes, which was twice as likely for patients in group B. Except for diabetes the prevalence of all diseases was comparable between the two groups. In conclusion, patients with mild ED should be closely evaluated for cardiovascular comorbidities.

Analysis of DAZ gene expression in a partial AZFc deletion of the human Y chromosome.

The azoospermia factor c (AZFc) region of the Y chromosome consists of repetitive amplicons and is therefore highly susceptible to structural rearrangements, such as deletions and duplications. The b2/b3 deletion is a partial AZFc deletion that is conventionally determined by the selective absence of sY1191 in sequence-tagged site polymerase chain reaction (PCR) and is generally believed to retain two of the four deleted in azoospermia (DAZ) genes on the Y chromosome. In the present study we determined the copy number and expression of DAZ genes in sY1191-negative individuals. Using a DAZ dosage PCR assay and Southern blot analysis we evaluated the expression of four DAZ genes in five of six sY1191-negative individuals. Furthermore, cloning and immunoblot analyses revealed that three or more DAZ genes are expressed in sY1191-negative testes with germ cells. The results indicate that the selective absence of sY1191 not only means b2/b3 deletion with two DAZ genes, but also includes another AZFc configuration with four DAZ genes. These results exemplify the prevalence of variations in the AZFc region of the human Y chromosome.

Does Preoperative Bladder Compliance Affect Long-Term Functional Outcomes after Laser Prostatectomy?

PURPOSE: We assessed the effects of preoperative bladder compliance on the long-term functional outcomes, especially focused on postoperative storage symptom changes, after laser prostatectomy. MATERIALS AND METHODS: From January 2008 to March 2014, 1,608 men who underwent laser prostatectomy, including holmium laser enucleation or photo-vaporization of the prostate, were included in the analysis. We divided patients into 3 groups according to bladder compliance on a baseline urodynamic study: <12.5, 12.5-25, ≥25 mL/cmH2O. A multivariable analysis was performed to determine the impact of bladder compliance on changes in long-term functional outcomes after laser prostatectomy. RESULTS: Bladder compliance was less than 12.5 mL/cmH2O in 50 (3.1%), 12.5-25 mL/cmH2O in 232 (14.4%) patients. As bladder compliance decreased, the baseline International Prostate Symptom (IPSS) total score and storage sub-score were increased; the voiding sub-score remain unchanged. At postoperative 12 and 36 months, absolute improvements in the IPSS total score and storage sub-score were higher in <12.5 mL/cmH2O group compared to other groups, although those were equivalent at postoperative 1 months. On the multivariable analysis, decreased bladder compliance <12.5 mL/cmH2O was significantly associated with superior improvement in storage sub-score at postoperative 36 months, although it was not associated with voiding sub-score. CONCLUSIONS: In patients with preoperative bladder compliance <12.5 mL/cmH2O, storage symptoms could be further improved at 36 months after laser prostatectomy compared to others. Thus, laser prostatectomy could be a considerable treatment option for patients with severely decreased bladder compliance.

Natural history of incidentally diagnosed prostate cancer after holmium laser enucleation of the prostate.

OBJECTIVES: There is no consensus on the management plan for incidental prostate cancer (IPCa) after holmium laser enucleation of the prostate (HoLEP). This study aims to investigate the natural course of this disease and suggest appropriate treatment in real clinical practice. METHODS: The medical records of a prospective cohort of patients with LUTS/BPH who underwent HoLEP between July 2008 and December 2020 at Seoul National University Hospital were retrospectively reviewed. Patients who underwent HoLEP for palliative purpose of prostate cancer control were excluded. The natural history of IPCa was assessed by the clinician in a descriptive manner for each treatment option. RESULTS: Among 2630 patients, 141 (5.4%) were diagnosed with IPCa after HoLEP. Pathologic T stage and magnetic resonance imaging results were highly associated with the physician's primary treatment decision-making for IPCa. Active surveillance (AS) was performed in 80% of patients, of whom 90% underwent follow-up without intervention, while the remaining 10% underwent deferred active treatment with a median follow-up of 46.3 months due to International Society of Urological Pathology grade group upgrading or increasing core involvement percentage. Meanwhile, 20% of patients underwent immediate active treatment. With a median follow-up period of 88.3 months after treatment, only one of 25 patients had biochemical recurrence. CONCLUSIONS: The incidence of IPCa after HoLEP was 5.4%, and among these, approximately 20% proceeded with immediate definitive therapy and an additional 6% ultimately received definitive therapy within a median of 4 years of AS but showed excellent oncological outcomes.

Risk Factors of Salvage Procedure for Refractory Morcellation During Holmium Laser Enucleation of the Prostate.

PURPOSE: We aimed to identify the risk factors for salvage procedure (SP) required for refractory adenomatous tissue resistant to morcellation during holmium laser enucleation of the prostate (HoLEP). METHODS: Patients who underwent HoLEP between January 2010 and April 2020 at Seoul National University Hospital were analyzed. SPs were defined as cases of conversion to resection of the prostatic tissue using an electrosurgical loop after morcellation or secondary morcellation a few days after surgery or conversion to open cystotomy. RESULTS: Among a total of 2,427 patients, 260 were identified as having SP (SP group) (transurethral resection-nodule [n = 250, 96.1%], secondary morcellation a few days after surgery [n = 9, 3.5%], and conversion to open cystotomy [n = 1, 0.4%]). Patients in the SP group were older and had higher 5-α reductase inhibitors use, higher prostate-specific antigen, larger total prostate volume, and larger transition zone volume (TZV) than those in the non-SP group. In the multivariable logistic regression analysis, only age and TZV were associated with SP. Compared to 40s and 50s, the odds ratios (ORs) were 3.84 in 60s (95% confidence interval [CI] 1.37-10.78, P = 0.011), 4.53 in 70s (95% CI, 1.62-12.62, P = 0.004), and 6.59 in 80s or older (95% CI, 2.23-19.46, P = 0.001). The ORs of the SP were analyzed per TZV quartile. Compared to TZV ≤ 20.3 mL, the OR was 3.75 in 32.0 mL < TZV ≤ 50.4 mL (95% CI, 2.00-7.04, P < 0.001) and 8.25 in 50.4 mL < TZV (95% CI, 4.06-16.77, P < 0.001). CONCLUSION: The risk of refractory morcellation increased in patients aged > 60 years or those with TZV > 32 mL. In order to more efficiently remove these resistant adenomas, it is necessary to develop more efficient morcellators in the future.

Efficacy and safety of avanafil for treating erectile dysfunction: results of a multicentre, randomized, double-blind, placebo-controlled trial.

UNLABELLED: Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Avanafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for treating erectile dysfunction (ED). Preclinical and clinical phase I studies showed that avanafil had enhanced selectivity, faster onset of action and a favourable side-effect profile relative to currently available PDE5 inhibitors. As the result of phase III clinical trial for the efficacy and safety of avanafil treatment (100 and 200 mg), taken as needed over a period of 12 weeks, in Korean patients with ED, avanafil is an effective and well-tolerated therapy for ED of broad-spectrum aetiology and severity. OBJECTIVE: • To evaluate the efficacy and safety of avanafil, a new potent selective phosphodiesterase type 5 (PDE5) inhibitor, in patients with erectile dysfunction (ED). PATIENTS AND METHODS: • The present study was a multicentre, randomized, double-blind, placebo-controlled, fix-dosed phase three clinical trial involving 200 patients with ED. • The subjects were treated with placebo or avanafil (100 or 200 mg) for 12 weeks and were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ). • The primary outcome variable was the change from baseline for IIEF erectile function domain (EFD) score. • The secondary outcome variables were SEP Q2 and Q3, the shift to normal rate (EFD ≥ 26), and response to the GAQ. RESULTS: • Compared with placebo, patients who took 100 or 200 mg of avanafil had significantly improved IIEF-EFD score. • There were similar results when comparing Q2 and Q3 in the SEP diary and the GAQ. • Flushing was the most common treatment-related adverse event. • Most adverse events were transient and mild or moderate in severity. CONCLUSION: • Avanafil is an effective and well-tolerated therapy for ED of broad-spectrum aetiology and severity.

Investigation of the effects of the level of glycemic control on erectile function and pathophysiological mechanisms in diabetic rats.

INTRODUCTION: Poor glycemic control is associated with erectile dysfunction (ED); however, differences in ED according to the level of glycemic control have been poorly investigated. AIM: The aim of this paper is to investigate the change in erectile function according to the level of glycemic control and to clarify the pathophysiological mechanism of diabetes-associated ED. METHODS: Streptozotocin was injected into 55 male Sprague-Dawley rats classified into four groups: control (group 1), diabetes with multiple insulin injections (group 2), diabetes with a single injection (group 3), and untreated diabetes (group 4). Daily insulin injections in groups 2 and 3 were administered for 4 weeks after 10 weeks of diabetic induction. MAIN OUTCOME MEASURES: The main outcome measures are the anova or Kruskal-Wallis tests to evaluate glycosylated hemoglobin (HbA1c), testosterone levels, the ratios of intracavernosal pressure to mean arterial pressure (ICP/MAP), area under the ICP curve to MAP (AUC/MAP), and changes in cavernous tissue and protein expression related to Rho kinase and nitric oxide pathways. RESULTS: HbA1c levels were different between pairs of groups. Group 4 showed the lowest erectile parameters and group 2 showed near normal level. No differences in erectile parameters were found between groups 1 and 2 or between groups 3 and 4, except the ratio of AUC to MAP for group 1 was significantly higher than that of group 2 (20 Hz stimulation). Decrease in erectile function of group 2 was related to decreased expression of nitrergic nitric oxide synthase or decreased testosterone level compared with group 1. Groups 2 and 3 showed significant differences in erectile parameters, which were associated with difference in apoptotic index. Groups 3 and 4 showed no differences in erectile parameters, although these groups had significant differences in apoptotic index, smooth muscle component, and protein expression ratios of phosphorylated to total myosin phosphatase target subunit 1, endothelial nitric oxide synthase, and Akt. CONCLUSIONS: Improvement in glycemic control assists recovery from diabetes-associated ED; however, only tight glycemic control can provide recovery from ED to a near normal status.

Chronic treatment with an oral rho-kinase inhibitor restores erectile function by suppressing corporal apoptosis in diabetic rats.

INTRODUCTION: It has been suggested that the up-regulation of the contractile RhoA/Rho-kinase (ROCK) signaling pathway is one of the important mechanisms for diabetes-associated erectile dysfunction (ED). However, the exact role of RhoA/ROCK signaling in the pathogenesis of diabetes-related ED has not been fully delineated. AIM: To determine whether the RhoA/ROCK pathway is involved in the regulation of corporal apoptosis and whether administration of insulin or fasudil, a specific ROCK inhibitor, could ameliorate ED in streptozotocin-induced diabetic rats. MAIN OUTCOME MEASURES: At 16 weeks after diabetes induction, erectile function was assessed by cavernous nerve stimulation. Penile tissue was assessed for apoptosis with terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling assay. Expression of myosin phosphatase target subunit 1 (MYPT1), protein kinase B (Akt), and phospho-endothelial nitric oxide synthase (eNOS) were evaluated by Western blot. Immunohistochemical study was carried out for smooth muscle alpha-actin, B-cell leukemia/lymphoma 2 (Bcl-2), and Bcl-2-associated X Protein (Bax). Activity of caspase-3 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) was also determined. METHODS: Male Sprague-Dawley rats (8 weeks old) were randomly divided into four groups: age-matched controls, diabetic controls, and diabetic rats treated with insulin (10 U/day, subcutaneous injection) or fasudil (30 mg/kg/day, oral) for the last 4 weeks of the 16 weeks after diabetes induction. RESULTS: Diabetic rats showed impairment of erectile function, increased MYPT1 phosphorylation, and corporal apoptosis. Expression of phospho-Akt, phospho-eNOS, and Bcl-2 were decreased, whereas activity of PTEN and caspase-3 and expression of Bax were increased. Treatment with fasudil normalized these molecular and histologic alterations, and restored erectile function. Insulin treatment showed similar effects to those of fasudil, however, the effects were smaller than fasudil. CONCLUSIONS: This study indicates that up-regulation of the penile RhoA/ROCK pathway in diabetic rats enhances corporal apoptosis via the PTEN/Akt pathway resulting in ED, which could be prevented by chronic treatment with fasudil.

Change of erectile function and responsiveness to phosphodiesterase type 5 inhibitors at different stages of streptozotocin-induced diabetes in rats.

INTRODUCTION: It has been suggested that risk of erectile dysfunction (ED) increases with duration of diabetes and phosphodiesterase type 5 inhibitors (PDE5I) are not as effective in treatment of diabetes-associated ED. However, few studies have investigated time-dependent change in erectile function during the course of diabetes. AIM: To investigate time-dependent change in erectile function and responsiveness to PDE5I in streptozotocin-induced diabetic rats and to understand the pathophysiology of diabetic ED. MAIN OUTCOME MEASURES: At 6, 8, 10, 12, and 14 weeks after diabetic induction, erectile function was assessed by cavernous nerve stimulation before and after administration of DA-8159, a novel PDE5I. Penile tissue was assessed for apoptosis with immunohistochemistry. Protein expression of Rho-kinase 2 (ROCK2), myosin phosphatase targeting subunit 1 (MYPT1), and endothelial nitric oxide synthase (eNOS) was evaluated by Western blot. METHODS: Streptozotocin was injected into 50 8-week-old male Sprague-Dawley rats, which were then classified into five diabetic groups according to the observation period. RESULTS: Diabetic rats maintained normal erectile responses until 6 weeks of diabetes. Following 8 weeks, the rats showed lower erectile responses at higher frequencies of nerve stimulation, which were normalized to control by administration of DA-8159. In contrast, erectile responses were significantly decreased in 10-week diabetic rats, and administration of DA-8159 resulted in partial recovery of normal responses. At more than 12 weeks, rats demonstrated severe deterioration of erectile function, which did not fully respond to PDE5I. Corporal apoptosis was significantly increased after 10 weeks. Upregulation of ROCK2 was found at 6 weeks, and was followed by an increase of MYPT1 phosphorylation. Phosphorylation of eNOS showed marked suppression at 6 weeks and remained lower during the experimental period. CONCLUSIONS: Impairment of erectile function was followed by decreased responsiveness to PDE5I during the course of diabetes. The RhoA/ROCK pathway played an important role in diabetes-associated ED.