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.

Quality of life after photo-selective vaporization and holmium-laser enucleation of the prostate: 5-year outcomes.

This study was aimed to compare serial long-term postoperative changes in quality-of-life (QoL) between photoselective-vaporization (PVP) using 120W-High-Performance-System and holmium-laser-enucleation (HoLEP) in benign-prostatic-hyperplasia (BPH) patients and to identify factors influencing the QoL improvement at the short-term, mid-term and long-term follow-up visits after surgery. We analyzed 1,193 patients with a baseline QoL-index ≥2 who underwent PVP (n = 439) or HoLEP (n = 754). Surgical outcomes were serially compared between the two groups at up to 60-months using the International-Prostatic-Symptom-Score (I-PSS), uroflowmetry, and serum PSA. We used logistic regression analysis to identify predictors of QoL improvement (a reduction in the QoL-index ≥50% compared with baseline) at the short-term (12-months), mid-term (36-months), and long term (60-months) follow-up after surgery. In both groups, the QoL-index was decreased throughout the entire follow-up period compared with that at baseline. There were no significant differences in postoperative changes from the baseline QoL-index between the two groups during the 48-month follow-up, except at 60-months. The degree of improvement in QoL at 60-months after HoLEP was greater than that after PVP. A lower baseline storage-symptom-subscore and a higher bladder-outlet-obstruction-index (BOOI) were independent factors influencing QoL improvement at the short-term. No independent factor influences QoL improvement at the mid- or long-term.

The effects of single versus combined therapy using LIM-kinase 2 inhibitor and type 5 phosphodiesterase inhibitor on erectile function in a rat model of cavernous nerve injury-induced erectile dysfunction.

We aimed to determine whether combination of LIM-kinase 2 inhibitor (LIMK2i) and phosphodiesterase type-5 inhibitor (PDE5i) could restore erectile function through suppressing cavernous fibrosis and improving cavernous apoptosis in a rat model of cavernous nerve crush injury (CNCI). Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows: (1) sham surgery (Group S), (2) CNCI (Group I), (3) CNCI treated with daily intraperitoneal administration of 10.0 mg kg-1 LIMK2i (Group I + L), (4) daily oral administration of 20.0 mg kg-1 udenafil, PDE5i (Group I + U), and (5) combined administration of 10.0 mg kg-1 LIMK2i and 20.0 mg kg-1 udenafil (Group I + L + U). Rats in Groups I + L, I + U, and I + L + U were treated with respective regimens for 2 weeks after CNCI. At 2 weeks after surgery, erectile response was assessed using electrostimulation. Penile tissues were processed for histological studies and western blot. Group I showed lower intracavernous pressure (ICP)/mean arterial pressure (MAP), lower area under the curve (AUC)/MAP, decreased immunohistochemical staining for alpha-smooth muscle (SM) actin, higher apoptotic index, lower SM/collagen ratio, increased phospho-LIMK2-positive fibroblasts, decreased protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) phosphorylation, increased LIMK2/cofilin phosphorylation, and increased protein expression of fibronectin, compared to Group S. In all three treatment groups, erectile responses, protein expression of fibronectin, and SM/collagen ratio were improved. Group I + L + U showed greater improvement in erectile response than Group I + L. SM content and apoptotic index in Groups I + U and I + L + U were improved compared to those in Group I. However, Group I + L did not show a significant improvement in SM content or apoptotic index. The number of phospho-LIMK2-positive fibroblasts was normalized in Groups I + L and I + L + U, but not in Group I + U. Akt/eNOS phosphorylation was improved in Groups I + U and I + L + U, but not in Group I + L. LIMK2/cofilin phosphorylation was improved in Groups I + L and I + L + U, but not in Group I + U. Our data indicate that combined treatment of LIMK2i and PDE5i immediate after CN injury could improve erectile function by improving cavernous apoptosis or eNOS phosphorylation and suppressing cavernous fibrosis. Rectification of Akt/eNOS and LIMK2/cofilin pathways appears to be involved in their improvement.

Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury.

We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg-1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.

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.

Role of Jun amino-terminal kinase (JNK) in apoptosis of cavernosal tissue during acute phase after cavernosal nerve injury.

The present study aimed to identify which mitogen-activated protein kinase (p38 or Jun amino-terminal kinase [JNK]) was involved in cavernosal apoptosis during the acute phase after cavernosal nerve crush injury (CNCI) in rats to ameliorate apoptosis of cavernosal tissue, such as smooth muscle (SM). A total of twenty 10-week-old male Sprague-Dawley rats were divided equally into two groups: sham surgery (S) and CNCI (I). The I group approximated the clinical situation of men undergoing radical prostatectomy using two 60-second compressions of both CNs with a microsurgical vascular clamp. At 2-week postinjury, erectile response was assessed using electrostimulation. Penile tissues were harvested for immunohistochemistry analysis of alpha-SM actin (α-SMA), western blot analysis, and double immunofluorescence analysis of α-SMA and phosphorylated p38 or JNK, as well as double immunofluorescent of TUNEL and phosphorylated p38 or JNK. At 2-week postinjury, the I group had a significantly lower intracavernous pressure (ICP)/mean arterial pressure (MAP) and a lower area under the curve (AUC)/MAP than the S group. The I group also exhibited decreased immunohistochemical staining of α-SMA, an increase in the number of SM cells positive for phosphorylated JNK, an increased number of apoptotic cells positive for phosphorylated JNK, and increased JNK phosphorylation compared with the S group. However, there was no significant difference in p38 phosphorylation expression or the number of SM cells positive for phosphorylated p38 between the two groups. In conclusion, our data suggest that JNK, not p38, is involved in cavernosal apoptosis during the acute phase after partial CN damage.

Patient Perception of Ejaculatory Volume Reduction After Holmium Laser Enucleation of the Prostate (HoLEP).

OBJECTIVE: To investigate patient perception of ejaculatory volume reduction after Holmium laser enucleation of the prostate (HoLEP). MATERIALS AND METHODS: A total of 192 patients were included in the analysis. All patients completed 6 self-developed, nonvalidated questionnaires. The questionnaires were composed of questions involving overall satisfaction, voiding symptom change, current experience of sexual intercourse, ejaculatory volume change, change of orgasmic intensity, and the patient's perception of postoperative ejaculatory volume reduction. Questionnaire results and clinical parameters were analyzed, and subgroup analysis according to the patient's perception was also performed. RESULTS: The median patient age was 66.0 years, and the mean total prostate volume and enucleated prostate volume was 61.9 ± 24.1 mL and 22.4 ± 14.0 mL, respectively. Among 192 patients, 91 patients had had sexual intercourse within the past 3 months. Ejaculatory volume changes after HoLEP were as follows: "total loss" (76.9%), "decreased" (18.7%), and "no change"(4.4%). Among the 87 patients who reported ejaculatory volume reduction, their perceptions of this issue were as follows: "feels better"(2.3%), "not a problem" (16.1%), "disappointed, but able to tolerate, owing to improvement of voiding symptoms" (73.6%), and "dissatisfied and want to reverse the situation"(8.0%). Decreased orgasmic intensity was present in 48 (52.8%) patients. There were significantly more patients who reported decreased orgasmic intensity among those who wanted to reverse the situation compared with the others (P = .027). CONCLUSION: Our study showed that most of the patients reported ejaculatory volume reduction and more than half of the patients reported decreased orgasmic intensity after HoLEP. We also found that patients' perceptions of ejaculatory volume reduction and orgasmic intensity were closely related to each other.

Do Effects on Bowel Patterns Imposed by Solifenacin Always Have Negative Impacts on Treating Patients with Overactive Bladder (OAB)?

OBJECTIVES: To investigate whether solifenacin intervention leads to any changes in bowel symptoms, and the types of impacts imposed on bowel symptoms in patients with overactive bladder (OAB). METHODS: This prospective, single-arm observational study included 40 adult patients who underwent anticholinergic treatment for OAB. Outcome measures were determined by examining differences in voiding and bowel symptoms, before and after patients commenced anticholinergic therapy. Patients were evaluated at baseline, 4, and 12 weeks via questionnaires on OAB and irritable bowel syndrome (IBS), side-effects, and overall satisfaction with the treatment. RESULTS: A total of 22 patients completed follow-up visits. Mean age was 62.1 ± 10.3 years. The most common side-effects were constipation and dry mouth. OAB symptom scores improved, with significant changes in urgency, incontinence, and total symptom scores and borderline significant changes in frequency. All bowel symptoms except diarrhea became aggravated. Average constipation and overall quality of life worsened with significance. Aside from the specific bowel habit changes, solifenacin treatment resulted in changes in patient status of IBS, as well. Patients were mostly satisfied with the treatment, despite some aggravations in discomfort due to defecation problems. CONCLUSIONS: This study shows that solifenacin treatment is effective for treating urinary incontinence but may lead to changes in bowel patterns and affects overall quality of life (QoL). Effects on bowel patterns imposed by solifenacin can be positive or negative, therefore, physicians should consider more holistic therapy by addressing overall bowel symptoms when treating OAB patients.

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.

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.

Factors affecting de novo urinary retention after Holmium laser enucleation of the prostate.

OBJECTIVE: Patients can experience urinary retention (UR) after Holmium laser enucleation of the prostate (HoLEP) that requires bladder distension during the procedure. The aim of this retrospective study is to identify factors affecting the UR after HoLEP. MATERIALS AND METHODS: 336 patients, which underwent HoLEP for a symptomatic benign prostatic hyperplasia between July 2008 and March 2012, were included in this study. Urethral catheters were routinely removed one or two days after surgery. UR was defined as the need for an indwelling catheter placement following a failure to void after catheter removal. Demographic and clinical parameters were compared between the UR (n = 37) and the non-urinary retention (non-UR; n = 299) groups. RESULTS: The mean age of patients was 68.3 (±6.5) years and the mean operative time was 75.3 (±37.4) min. Thirty seven patients (11.0%) experienced a postoperative UR. UR patients voided catheter free an average of 1.9 (±1.7) days after UR. With regard to the causes of UR, 24 (7.1%) and 13 (3.9%) patients experienced a blood clot-related UR and a non-clot related UR respectively. Using multivariate analysis (p<0.05), we found significant differences between the UR and the non-UR groups with regard to a morcellation efficiency (OR 0.701, 95% CI 0.498-0.988) and a bleeding-related complication, such as, a reoperation for bleeding (OR 0.039, 95% CI 0.004-0.383) or a transfusion (OR 0.144, 95% CI 0.027-0.877). Age, history of diabetes, prostate volume, pre-operative post-void residual, bladder contractility index, learning curve, and operative time were not significantly associated with the UR (p>0.05). CONCLUSIONS: De novo UR after HoLEP was found to be self-limited and it was not related to learning curve, patient age, diabetes, or operative time. Efficient morcellation and careful control of bleeding, which reduces clot formation, decrease the risk of UR after HoLEP.

Time-dependent changes of erectile function in diabetic rats: role of systemic endothelial dysfunction.

PURPOSE: To understand the potential contribution of systemic endothelial dysfunction to diabetic erectile dysfunction, and the time course of erectile dysfunction in a streptozotocin (STZ)-induced diabetic rat model. MATERIALS AND METHODS: Among 84, 12-week-old Sprague-Dawley rats, 48 rats received intraperitoneal STZ and were classified into six groups of diabetes by the period of observation (n=8). The remaining 36 rats were also grouped, similar to the diabetic groups, and served as normal controls. After 4, 6, 8, 10, 12, and 14 weeks of diabetes (serum glucose >250 mg%), all rats underwent cavernous nerve electrostimulation (3 V, 0.2 ms, 30 sec) with varying frequency (2.5~20 Hz). At the end of the study, 8 ml of blood was taken to measure the plasma markers of endothelial function and glycosylated hemoglobin. RESULTS: Compared to the control, significant reduction of erectile response was not observed until eight weeks after diabetes induction. The diabetic rats had elevation of all plasma markers except for l-selectin. However, the correlation analysis revealed that no systemic marker of endothelial dysfunction was associated with change in erectile function. Only the level of hemoglobin A1c (HbA1c) showed a modest but significant correlation with the peak intracavernosal pressure, corrected by mean arterial pressure (ρ=-0.183), and the area under the curve of the cavernosometry (ρ=-0.207). CONCLUSIONS: Significant reduction of erectile function was not observed until eight weeks after the induction of diabetes. Except for HbA1c, there was no systemic marker associated with endothelial activation and erectile function in the diabetic rats.

Effect of dutasteride on the expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in rat and human prostate tissue.

OBJECTIVE: To evaluate the effects of dutasteride on the expression of angiogenesis markers in rat and human prostates. MATERIAL AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of six each according to dutasteride dose, including the control group (regular diet), 2.5 mg group (2.5 mg/kg dutasteride) and 5.0 mg group (5.0 mg/kg dutasteride). A total of 41 patients awaiting transurethral resection of the prostate (TURP) were divided into two groups: 20 patients received no medication and 21 received 0.5 mg dutasteride daily for 2-4 weeks until TURP. RESULTS: At 2 weeks, dutasteride effected a significant decrease in body weight and prostate weight compared with the control rat group. Analysis by reverse transcription-polymerase chain reaction and Western blot revealed that hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression was lower in the dutasteride-treated groups than in the control group, except for HIF-1alpha protein. HIF-1alpha and VEGF expression was similar in the 2.5 mg and 5.0 mg groups. Human prostate tissues demonstrated homogeneous staining of HIF-1alpha and VEGF with regard to extent, intensity and intracellular location in both groups. There was no significant difference in microvessel density between the two groups. CONCLUSIONS: The expression of HIF-1alpha and VEGF in rat prostates is suppressed by dutasteride. However, less than 4 weeks of dutasteride administration does not suppress the expression of HIF-1alpha, VEGF and microvessel density in human prostate tissue. Further clinical investigation with dutasteride including a larger, placebo-controlled study is warranted to establish the mechanism and duration of dutasteride.

The one year outcome after KTP laser vaporization of the prostate according to the calculated vaporized volume.

The aim of this study was to develop a new simple method for measuring the vaporized volume and to evaluate the outcome of high-power potassium-titanyl-phosphate (KTP) photoselective laser vaporization. A total of 65 patients, with a mean age of 67.7 yr (range 53 to 85), were included in the primary analysis. The vaporized volume was calculated as the pre-operative volume minus the immediate post-operative volume plus the volume of the defect. For all patients, the subjective and objective parameters improved significantly after surgery. Six and 12 months after surgery, the group with a smaller vaporized volume (<15 g) had a lower reduction of the mean International Prostate Symptom Score (P=0.006 and P=0.004) and quality of life index (P=0.006 and P=0.004) when compared to the group with a greater vaporized volume (>or=15 g). There were no differences in the change of the maximum flow rate and post-void residual based on the vaporized volume. Our findings suggest that the subjective improvement, after a high-power KTP laser vaporization, may be dependent on the vaporized volume obtained after the procedure.

Chronic treatment with a type 5 phosphodiesterase inhibitor suppresses apoptosis of corporal smooth muscle by potentiating Akt signalling in a rat model of diabetic erectile dysfunction.

OBJECTIVES: To examine whether chronic treatment with a type 5 phosphodiesterase inhibitor (PDE5I) could suppress corporal apoptosis via potentiation of Akt signalling in diabetic erectile dysfunction. METHODS: Sprague-Dawley rats (12 wk old) were divided into three groups (n=12 in each): normal control, diabetes (DM), and diabetes treated with PDE5I (DM+PDE5I). The rats in the diabetic groups received a single injection of streptozotocin (50mg/kg), and from 8 wk after establishment of diabetes, DM and DM+PDE5I were treated with vehicle and PDE5I (SK-3530, 10mg/kg), respectively, for 4 wk. After 12 wk of streptozotocin injections, six rats in each group underwent cavernosometry with cavernous nerve electrostimulation (2V, 0.2 ms, 50s, 2.5-20 Hz). The penile tissues from the remaining six rats were used for immunohistochemical evaluation of apoptosis, immunoblotting for the phosphorylation of Akt and its downstream molecule Bad, and a colorimetric assay of caspase activity. RESULTS: Rats in the DM group showed markedly lower erectile parameters than those in the control group, whereas rats in the DM+PDE5I group showed normalized results. Despite persistent hyperglycaemia, PDE5I treatment significantly reduced the mean apoptotic index (39.6+/-4.6 vs. 21.3+/-1.7, p<0.05). Densitometry revealed significantly higher levels of Akt and Bad phosphorylation, implying inhibition of pro-apoptotic stimuli. PDE5I treatment also significantly inhibited the activities of cavernosal caspase 3 and caspase 9, the main effectors of apoptosis. CONCLUSIONS: Chronic treatment with PDE5I activated Akt signalling, which suppressed pro-apoptotic stimuli and maintained erectile function in rat model of diabetic erectile dysfunction.

Percutaneous posterior tibial nerve stimulation in patients with chronic pelvic pain: a preliminary study.

BACKGROUND: We evaluated the clinical effect of intermittent percutaneous posterior tibial nerve stimulation (PTNS) in patients with chronic pelvic pain (CPP). METHODS: A total of 15 patients (10 women and 5 men, mean age 60.0 years, range 41-78) with CPP were enrolled in an open prospective clinical trial. The patients had 12 weekly outpatient treatment sessions, each lasting 30 min. All patients were evaluated by history, physical as well as urological examination, the Visual Analogue Scale (VAS) for pain and urgency, the International Prostate Symptom Score, and a 3-day frequency-volume chart. RESULTS: After 12 weeks of PTNS, 9 (60%) and 3 patients (30%) had an improvement of >50% and 25-50% in the VAS score for pain, respectively. Six patients (40%) ended up with a mean VAS <3. Mean VAS for pain changed from 8.1 +/- 0.2 at baseline to 4.1 +/- 0.6 after 12 weeks of treatment (p < 0.01). Mean VAS for urgency changed from 4.5 +/- 1.0 at baseline to 2.7 +/- 0.7 after 12 weeks of treatment (p < 0.05). However, there was no statistically significant improvement in the International Prostate Symptom Score. There was no statistically significant difference in the number of voids and bladder volumes either. CONCLUSIONS: Our findings suggest that PTNS may improve pain symptoms for over half of the patients with CPP. Long-term follow-up studies are needed to verify these preliminary results.

Factors influencing practices for chronic prostatitis: a nationwide survey of urologists in South Korea.

BACKGROUND: We investigated the influence of physicians' attitudes on the treatment of chronic prostatitis, and attempted to correlate demographic and professional characteristics with patterns of therapy regarding chronic prostatitis. METHODS: Probability samples were drawn from the Korean Urological Association Registry of Physicians, and a random sample of 850 Korean urologists were asked to complete a questionnaire which explored practice characteristics, attitudes, and diagnostic and treatment strategies for the management of chronic prostatitis. The returned questionnaires were statistically analysed. RESULTS: Of the 850 questionnaires sent, 302 were returned, and 275 of those were included in the final analysis (response rate 32.4%). Multivariate logistic regression analysis indicated that the type of hospital (P < 0.001) and belief that culture tests helped diagnose chronic prostatitis (P = 0.001) were the most determinant factors with respect to the routine performance or non-performance of culture tests. Most Korean urologists (96.4%) prescribed antibiotics for the primary treatment of chronic prostatitis. Even when primary antibiotic treatment was unsuccessful, urologists frequently prescribed a second course of antibiotics (57.8%). In the multivariate model used, the likelihood of prescribing antibiotics as a secondary treatment varied by the type of hospital, with 0.4-fold odds (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.21-0.87; P = 0.019) of the practice occurring in university hospitals, as opposed to primary clinics. According to the same model, the belief that culture tests help to diagnose chronic prostatitis was also an independent influencing factor (OR, 2.29; 95% CI, 1.39-3.77; P = 0.001), whereas the actual performance of culture tests had no statistical significance. CONCLUSION: Our findings suggest that the personal beliefs and professional characteristics of physicians may influence the diagnosis and treatment of chronic prostatitis in Korea.