Prognostic Role of Preoperative Neutrophil-To-Lymphocyte Ratio (NLR) and Recurrence at First Evaluation after Bacillus Calmette-Guérin (BCG) Induction in Non-Muscle-Invasive Bladder Cancer.

We investigated the prognosis of BCG induction-only treatment and non-complete response (CR) at the first 3-month evaluation and examined factors associated with CR. In total, 209 patients with moderate- and high-risk NMIBC who received BCG induction-only treatment between 2008 and 2020 were retrospectively analyzed. Recurrence-free survival (RFS) and progression-free survival (PFS) were assessed based on the initial NMIBC stage. PFS and associated factors of non-CR compared to CR were also assessed. Initial T1 high-grade (HG) (n = 93) had poorer RFS and PFS after BCG induction-only treatment than Ta low-grade (LG) (p = 0.029, p = 0.002). Non-CR (n = 37) had a different neutrophil-to-lymphocyte ratio (NLR) (2.81 ± 1.02 vs. 1.97 ± 0.92) and T staging from CR (p < 0.001, p = 0.008). T1HG recurrence was associated with a worse PFS compared to non-T1HG (13.7 months vs. 101.7 months, p < 0.001). There was no difference in PFS between T1HG and T1LG. T1 and NLR were predictors of response at 3 months in multivariable analysis (p = 0.004, p = 0.029). NLR was also found to be an associated factor with RFS and PFS of bladder cancer (p < 0.001, p < 0.001). BCG induction-only treatment was effective for high-risk TaLG but not for T1HG. T1HG recurrence at 3 months after BCG induction has a poor prognosis for bladder cancer. Preoperative NLR and T1 were predictors of non-CR, and NLR was also associated with the long-term prognosis of bladder cancer.

Management of Male Infertility with Coexisting Sexual Dysfunction: A Consensus Statement and Clinical Recommendations from the Asia-Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA).

Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients' factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: "low libido", "erectile dysfunction", "ejaculatory dysfunction", "premature ejaculation", "retrograde ejaculation", "delayed ejaculation", "anejaculation", and "orgasmic dysfunction" between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socio-economic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient's individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.

Transitional zone prostate cancer: Performance of texture-based machine learning and image-based deep learning.

This study is aimed to explore the performance of texture-based machine learning and image-based deep-learning for enhancing detection of Transitional-zone prostate cancer (TZPCa) in the background of benign prostatic hyperplasia (BPH), using a one-to-one correlation between prostatectomy-based pathologically proven lesion and MRI. Seventy patients confirmed as TZPCa and twenty-nine patients confirmed as BPH without TZPCa by radical prostatectomy. For texture analysis, a radiologist drew the region of interest (ROI) for the pathologically correlated TZPCa and the surrounding BPH on T2WI. Significant features were selected using Least Absolute Shrinkage and Selection Operator (LASSO), trained by 3 types of machine learning algorithms (logistic regression [LR], support vector machine [SVM], and random forest [RF]) and validated by the leave-one-out method. For image-based machine learning, both TZPCa and BPH without TZPCa images were trained using convolutional neural network (CNN) and underwent 10-fold cross validation. Sensitivity, specificity, positive and negative predictive values were presented for each method. The diagnostic performances presented and compared using an ROC curve and AUC value. All the 3 Texture-based machine learning algorithms showed similar AUC (0.854-0.861)among them with generally high specificity (0.710-0.775). The Image-based deep learning showed high sensitivity (0.946) with good AUC (0.802) and moderate specificity (0.643). Texture -based machine learning can be expected to serve as a support tool for diagnosis of human-suspected TZ lesions with high AUC values. Image-based deep learning could serve as a screening tool for detecting suspicious TZ lesions in the context of clinically suspected TZPCa, on the basis of the high sensitivity.

Lowering the percent body fat in the obese population might reduce male lower urinary tract symptoms.

PURPOSE: This study aimed to investigate the practicality of percent body fat (PBF), calculated using bioelectrical impedance analysis (BIA), in predicting benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). METHODS: This study included 844 men who underwent medical checkups at our institution between 2014 and 2022. Demographic characteristics, serum PSA levels, and prostate volume were collected using TRUS. BPH was defined as a prostate volume ≥ 30 cc. Subjects were divided into two groups according to their quartiles of PBF: the normal PBF group (first to third quartile; PBF < 27.9%) and the high PBF group (fourth quartile; PBF ≥ 27.9%). Characteristics between the groups were compared using the chi-square test and Student's t-test. Multivariate logistic regression analysis was performed to evaluate risk factors for BPH and severe LUTS. RESULTS: The prostate volume (25.21 ± 8.4 vs 27.30 ± 9.0, p = 0.005) and percentage of BPH (22.9% vs. 32.1%, p = 0.007) were greater in the high PBF group. After multivariate analysis, old age (OR = 1.066, p < 0.001), higher appendicular skeletal muscle mass index (ASMI) (OR = 1.544, p = 0.001), and PBF ≥ 27.9% (OR = 1.455, p = 0.037) were risk factors for BPH. Larger prostate volume (OR = 1.035, p = 0.002) and PBF ≥ 27.9% (OR = 1.715, p = 0.025) were risk factors for severe LUTS. However, a greater ASMI had a protective effect against severe LUTS (OR = 0.654, p = 0.011). CONCLUSIONS: This study shows that PBF and ASMI are useful for predicting BPH/LUTS. We suggest that lowering PBF to the normal range in a population with high PBF might prevent BPH, while lowering PBF and maintaining adequate ASMI could lower LUTS.

Chronic treatment with a combination of hepatocyte growth factor and JNK inhibitor ameliorates cavernosal veno-occlusive dysfunction: a rat model of cavernous nerve injury.

BACKGROUND: Structural alterations of the penis, including cavernosal apoptosis and fibrosis, induce venous leakage into the corpus cavernosum or cavernosal veno-occlusive dysfunction, a key pathophysiology associated with erectile dysfunction after radical prostatectomy. We hypothesized that the effect of JNK inhibitors on reducing apoptosis and hepatocyte growth factor (HGF) on inducing tissue regeneration could be another treatment mechanism of erectile dysfunction after radical prostatectomy. AIM: To investigate whether JNK inhibition combined with intracavernosal administration of HGF can completely preserve cavernosal veno-occlusive function (CVOF) in a rat model of erectile dysfunction induced via bilateral cavernosal nerve crush injury (CNCI). METHODS: A total of 42 male Sprague-Dawley rats were randomly assigned to sham control (group S), CNCI (group I), and CNCI treated with a combination of JNK inhibitor and HGF (group J + H) for 5 weeks after surgery. OUTCOMES: Rats in each group were evaluated via dynamic infusion cavernosometry (DIC), caspase-3 activity assay, Masson trichrome staining, immunohistochemical staining of α-smooth muscle actin, and immunoblotting at 5 weeks after surgery. RESULTS: Regarding CVOF, group I showed decreased papaverine response, increased maintenance, and drop rates of DIC when compared with group S. Group J + H showed significant improvement in the 3 DIC parameters vs group I. No differences in the 3 DIC parameters were found between group J + H and group S. Regarding the structural integrity of the corpus cavernosum, group I showed increased caspase-3 activity, decreased smooth muscle (SM):collagen ratio, decreased SM content, decreased protein expression of PECAM-1, and decreased phosphorylation of c-Jun and c-Met. Group J + H showed significant attenuation in histologic and molecular derangement as compared with group I. There were no differences in caspase-3 activity, SM content, SM:collagen ratio, PECAM-1 protein expression, c-Jun phosphorylation, and c-Met phosphorylation between groups J + H and S. CLINICAL IMPLICATIONS: Our results suggest that antiapoptotic and regenerative therapy for the corpus cavernosum is a potential mechanism of penile rehabilitation after radical prostatectomy. STRENGTHS AND LIMITATIONS: This study provides evidence that combination treatment of JNK inhibitor and HGF preserves erectile function by restoring corporal SM and endothelium. However, additional human studies are needed to confirm the clinical effect. CONCLUSION: Chronic treatment with JNK inhibitor and HGF may preserve CVOF to levels comparable to sham control by preserving the structural integrity of the corpus cavernosum and so represents a potential therapeutic option for preventing the development of cavernosal veno-occlusive dysfunction.

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.

A Nationwide Study of Differences in Surgical Treatment Rates and Oncological Outcomes for Prostate Cancer according to Economic Status and Region.

PURPOSE: We investigated the effects of economic status (classified based on insurance type and residential area) on oncological outcomes of prostate cancer using a nationwide database. We additionally investigated oncological outcomes based on economic status and residential area in patients who underwent surgical treatment. Materials and Methods: The study included 75,518 men with newly diagnosed prostate cancer between 2009 and 2018 in whom oncological outcomes were investigated based on economic status and residential area. Among the 75,518 men with prostate cancer, the data of 29,973 men who underwent radical prostatectomy were further analyzed. Multivariate analysis was performed to determine the effects of economic status and residential area on postoperative oncological outcomes. RESULTS: Among the 75,518 patients with prostate cancer, 3,254 (4.31%) were medical aid beneficiaries. The 5-year overall survival rates were 81.2% and 64.8% in the health insurance and medical aid groups, respectively. Radical prostatectomy was more common in the health insurance group, and surgical intervention was significantly affected by the residential area. Among patients who underwent surgery, 5-year androgen deprivation therapy-free and overall survival were better in the health insurance group. Multivariate analysis showed that insurance type and residential area were significantly associated with the androgen deprivation therapy-free and overall survival after adjustment for other variables. CONCLUSION: Economic status and residential area were shown to affect not only treatment patterns but also post-diagnosis and postoperative oncological outcomes. Political support for early diagnosis and appropriate treatment of prostate cancer is warranted for medically vulnerable populations.

A smart, practical, deep learning-based clinical decision support tool for patients in the prostate-specific antigen gray zone: model development and validation.

OBJECTIVE: Despite efforts to improve screening and early detection of prostate cancer (PC), no available biomarker has shown acceptable performance in patients with prostate-specific antigen (PSA) gray zones. We aimed to develop a deep learning-based prediction model with minimized parameters and missing value handling algorithms for PC and clinically significant PC (CSPC). MATERIALS AND METHODS: We retrospectively analyzed data from 18 824 prostate biopsies collected between March 2003 and December 2020 from 2 databases, resulting in 12 739 cases in the PSA gray zone of 2.0-10.0 ng/mL. Dense neural network (DNN) and extreme gradient boosting (XGBoost) models for PC and CSPC were developed with 5-fold cross-validation. The area under the curve of the receiver operating characteristic (AUROC) was compared with that of serum PSA, PSA density, free PSA (fPSA) portion, and prostate health index (PHI). RESULTS: The AUROC values in the DNN model with the imputation of missing values were 0.739 and 0.708 (PC) and 0.769 and 0.742 (CSPC) in internal and external validation, whereas those of the non-imputed dataset were 0.740 and 0.771 (PC) and 0.807 and 0.771 (CSPC), respectively. The performance of the DNN model was like that of the XGBoost model, but better than all tested clinical biomarkers for both PC and CSPC. The developed DNN model outperformed PHI, serum PSA, and percent-fPSA with or without missing value imputation. DISCUSSION: DNN models for missing value imputation can be used to predict PC and CSPC. Further validation in real-life scenarios are need to recommend for actual implementation, but the results from our study support the increasing role of deep learning analytics in the clinical setting. CONCLUSIONS: A deep learning model for PC and CSPC in PSA gray zones using minimal, routinely used clinical parameter variables and data imputation of missing values was successfully developed and validated.

The role of the serum 25-OH vitamin D level on detecting prostate cancer in men with elevated prostate-specific antigen levels.

We aimed to determine whether vitamin D levels before prostate biopsy have diagnostic value for clinically significant prostate cancer. The study cohort included patients who underwent prostate biopsy. A total of 224 patients were enrolled in our study and serum vitamin D levels were measured from February 2016 to December 2019 in routine laboratory tests. To determine the relationship between vitamin D levels and aggressiveness of prostate cancer, we used logistic multivariate analysis. Based on the histopathological results of patients who underwent radical prostatectomy, the serum vitamin D level was significantly lower with the large tumor volume group. In the univariate analysis, the prostate cancer diagnosis rate was associated with low vitamin D levels. Low vitamin D level is negatively correlated with clinically significant prostate cancer (biopsy Gleason score of 7 or higher) in the univariate (Odds ratio [OR], 0.955; P < 0.001) and multivariate (OR, 0.944; P = 0.027) analyses. In conclusion, we found that the incidence of clinically significant prostate cancer might related to low vitamin D level in the Asian population. In the future, a larger population and prospective study are needed.

Association between life-style, metabolic syndrome and lower urinary tract symptoms and its impact on quality of life in men ≥ 40 years.

We aimed to assess the relationship between lifestyle-related variables, metabolic syndrome, and lower urinary tract symptoms (LUTS) in men ≥ 40 years. We also assessed the impact of these variables on quality of life. From 2014 to 2020, 5355 men who underwent health check-ups with I-PSS questionnaires at our institute were included in the analysis. The impact of LUTS on sleep disorders and moderate to severe degrees of stress were assessed. Multivariate analysis was performed to determine the variables associated with LUTS and prostate volume. Moderate and severe LUTS were present in 1317 (24.6%) and 211 (3.9%) men, respectively. Moderate and severe LUTS were significantly associated with the presence of sleep disorders and stress. On multivariable analysis, age, amount of life-long smoking, marital status, income, job, and decreased HDL-cholesterol were associated with the presence of moderate to severe LUTS. Although older age and the amount of life-long smoking was associated with both voiding and storage sub-score, socioeconomic status, including marital status and income were only associated with storage sub-score. In men ≥ 40 years, stable socioeconomic status, in addition to older age, and life-long smoking amount are associated with the presence of moderate to severe LUTS, which worsens sleep quality and stress level, by worsen storage sub-score.

Significance of a decrease in the proportion of detrusor muscle to bladder wall for non-invasive diagnosis of detrusor underactivity in men with lower urinary tract symptoms.

To investigate the significance of detrusor muscle thickness (DMT) to bladder wall thickness (BWT) ratio as a detrusor-sarcopenia and a consistently applicable factor for noninvasive diagnosis of detrusor underactivity (DU). We prospectively performed a urodynamic study of 100 male with medical refractory lower-urinary-tract-symptoms during 2017-2019. The DMT, BWT and DMT/BWT ratio were measured by ultrasonography every 50 mL during bladder filling, and were analyzed for non-invasive diagnosis of DU and prediction of prostate surgery outcome with questionnaire and the maximum-flow-rate. Of the 94 patients, DU was urodynamically diagnosed in 24 (25.5%). The DMT/BWT ratio was maintained in all patients until the 50% of the maximum cystometric capacity (MCC), and then rapidly decreased. At 20% of the MCC, the DMT/BWT ratio was significantly lower in the DU group (44.0 ± 4.9% vs. 49.4 ± 6.7%, p = 0.008). The DMT/BWT ratio of less than 47.5% at 20% of the MCC showed the ideal accuracy for diagnosing DU (AUC = 0.763), and was a predictor of failure at 12 months after prostate surgery (OR 8.78, p = 0.024). A DMT/BWT ratio of less than 47.5% at 20% of the MCC is a consistently applicable factor for non-invasive diagnosis of DU and could also be considered detrusor-sarcopenia.

Prediction of surgical margin status and location after radical prostatectomy using positive biopsy sites on 12-core standard prostate biopsy.

We evaluated the surgical margin status after radical prostatectomy according to sites positive for prostate cancer on standard 12-core transrectal ultrasound-guided prostate biopsy. Among patients who underwent radical prostatectomy at Boramae Medical Center, 520 patients with preoperative prostate-specific antigen (PSA) level < 20 ng/mL and locally confined prostate cancer on preoperative magnetic resonance imaging, treated with nerve-sparing radical prostatectomy, were included in the analysis. The surgical margin was positive for cancer in 166 (31.9% of the total) patients. The preoperative PSA level (9.3 vs. 8.0, ng/mL p = 0.001) and number of positive cores on 12-core prostate biopsy (4.1 vs. 3.4, p = 0.003) were significantly higher in patients with positive surgical margins. Moreover, the biopsy Gleason grade was higher in patients with positive surgical margins (p = 0.001). However, the pathologic Gleason grade and tumor volume were equivalent between the 2 groups. On multivariate analysis, the detection of prostate cancer on anterior lateral biopsy was associated with an increased rate of positive surgical margins (hazard ratio [HR]: 1.781, p = 0.008) after adjusting for other variables. Anterior lateral (HR: 1.919, p = 0.020), basal lateral (HR: 9.176, p < 0.001), basal medial (HR: 3.302, p = 0.031), and mid lateral (HR: 2.501, p = 0.044) biopsies were associated with positive apical, posterior, basal, and lateral surgical margins, respectively, after adjusting for other variables. The sites of prostate cancer on standard 12-core prostate biopsy could be useful for predicting surgical margin positivity after radical prostatectomy. In other words, clinicians should consider the sites of prostate cancer on prostate biopsy to reduce margin positivity after radical prostatectomy.

Changes in kidney function according to ischemia type during partial nephrectomy for T1a kidney cancer.

To compare the postoperative estimated-glomerular-filtration-rate (eGFR) and parenchymal changes between cold ischemia and zero/selective ischemia for a T1a mass. We analyzed 104 patients who underwent open partial nephrectomy with cold ischemia (53) or zero/selective ischemia (51) for T1a between 2008 and 2018 to determine postoperative renal function changes and associated factors. Postoperative renal function was expressed as (postoperative-eGFR - preoperative-eGFR)/preoperative-eGFR × 100%. Parenchymal enhancement and thicknesses of the ipsilateral kidney as tissue changes were measured on postoperative CT to identify the correlation with the renal function change. Patients with 10% or 25% decrease in eGFR were significantly more in the cold ischemia group (p = 0.032, p = 0.006). On multivariable analysis, preoperative eGFR, ischemic type, and percent change of parenchymal thickness were identified to be significantly associated with postoperative 12 months renal function (B = - 0.367, p = 0.020; B = 6.788, p = 0.042; B = 0.797, p = 0.029). Change in parenchymal thickness was negatively correlated with changes in postoperative renal function (r = - 0.277, p = 0.012). Changes in eGFR were associated with a decrease in parenchymal thickness and the type of ischemic technique. Zero/selective ischemia during partial nephrectomy may have an advantage in preserving postoperative renal function compared to cold ischemia.

Restoring erectile function by combined treatment with JNK inhibitor and HDAC inhibitor in a rat model of cavernous nerve injury.

BACKGROUND: The main pathophysiologic conditions of erectile dysfunction (ED) after radical prostatectomy are considered to be corporal fibrosis and apoptosis induced by cavernosal nerve (CN) injury. OBJECTIVES: In a rat model of CN crush injury (CNCI), we investigated whether combination treatment with JNK inhibitor (JNKi), SP600125, and HDAC inhibitor (HDACi), suberoylanilide-hydroxamic-7 acid (SAHA), for 2 weeks after CNCI would restore erectile function by suppressing fibrosis and apoptosis through normalization of JNK and HDAC pathways. MATERIALS AND METHODS: Seventy 12-week-old rats were randomly divided into five groups: Sham surgery, CNCI alone, CNCI treated with daily intraperitoneal injection of 10 mg/kg JNKi, CNCI treated with daily oral administration of 25.0 mg/kg HDACi, and CNCI daily treated with a combination. Two weeks after CNCI, we investigated the erectile response to electrostimulation and conducted histological staining, caspase-3 activity assay, and western blot analysis. RESULTS: CNCI alone resulted in significantly reduced intracavernosal pressure/mean arterial pressure (MAP) and area under the curve/MAP, decreased smooth muscle (SM)/collagen ratio and SM content, higher caspase-3 activity, and increased protein levels of total HDAC3, transforming growth factor (TGF)-ß, fibronectin, and c-Jun phosphorylation, compared with the Sham surgery. The CNCI groups exposed to JNKi, HDACi or both showed improvements in erectile-responses and SM/collagen ratio, compared to the CNCI alone. The combined treatment showed additional improvement in erectile responses at 1.0V stimulation and in SM/collagen ratio compared to the single agent treatment. SM content, caspase-3 activity, and c-Jun phosphorylation improved in the two CNCI groups exposed to JNKi. The two CNCI groups exposed to HDACi showed normalization of protein levels of HDAC3, fibronectin, and TGF-ß. DISCUSSION AND CONCLUSIONS: The combined administration of JNKi and HDACi during the acute phase after CNCI in rats can preserve ED by suppressing cavernosal fibrosis and apoptosis by normalizing the HDAC/TGF-ß and JNK pathways.

Restoration of erectile function by a combination of antiapoptosis by JNK inhibitor and preservation of smooth muscle or endothelium by hepatocyte growth factor in a rat model of cavernous nerve injury.

BACKGROUND: Because of structural alterations in the corpus cavernosum after radical prostatectomy (RP), post-RP erectile dysfunction remains a very difficult condition to treat. We aimed to determine if the combined administration of a Jun-amino terminal kinase (JNK) inhibitor and hepatocyte growth factor (HGF) in the immediate post-injury period would restore erectile function by antiapoptotic and pro-regenerative effects through the rectification of molecular pathways related to the structural integrity of the penis in a rat model of bilateral cavernosal nerve crush injury (CNCI). METHODS: A total of 70 rats were divided into five groups: Sham surgery (S), CNCI (I), and once-daily intraperitoneal administration of 10.0 mg/kg JNK inhibitor + twice-weekly intracavernosal administration of low-dose (2.1 µg), medium-dose (4.2 µg), or high-dose (8.4 µg) HGF (I + J + LH or I + J + MH or I + J + HH, respectively) in the immediate post-injury period. Erectile responses to electrostimulation (1.0, 3.0, and 5.0 V), histological staining, caspase-3 activity, and Western blotting were evaluated 9 days after surgery. RESULTS: Group I showed lower intracavernosal pressure (ICP)/mean arterial pressure (MAP) after stimulation at each voltage, lower area under the curve (AUC)/MAP after stimulation at each voltage, less smooth muscle (SM) content, a lower SM/collagen ratio, higher caspase-3 activity, increased cJun phosphorylation, decreased protein expression of PECAM-1, decreased cMet phosphorylation, and decreased endothelial nitric oxide synthase (eNOS) phosphorylation compared to Group S. The SM content, SM/collagen ratio, protein expression of ICP/MAP, or AUC/MAP after stimulation at each voltage in Group I + J + LH were partially restored, despite the normalization of cJun phosphorylation and caspase-3 activity. The ICP/MAP, AUC/MAP, caspase-3 activity, SM content, protein expression of PECAM-1, cJun phosphorylation, cMet phosphorylation, and eNOS phosphorylation in both Groups I + J + MH and I + J + HH were restored to the levels observed in Group S, while the SM/collagen ratio was significantly improved but not completely normalized. CONCLUSIONS: Our data indicated that the combined administration of a JNK inhibitor and medium or high-dose HGF to nerve-injured rats in the immediate post-injury period after CNCI may restore erectile function to a level comparable to the normal level by suppressing cavernosal apoptosis and preserving the integrity of SM or endothelium via rectification of the cJun and cMet/eNOS pathways.

Changing Trends in Sexual Debut Age in the Korean Internet Sexuality Survey.

PURPOSE: To evaluate changing trends in relation to the sexual debut age and socioeconomic status (SES) in Korea. MATERIALS AND METHODS: The Korean Internet Sexuality Survey (KISS) was conducted for in 2004, 2006, 2014, and 2016. We sent emails and surveyed people registered at an Internet survey agency. To determine the changing trends in sexual debut age, we collected and compared the responses of females in their 20s in 2004 (n=253) and 2014 (n=131) and collected and compared the responses of males in their 20s in 2006 (n=87) and 2016 (n=200). RESULTS: In females, SES factors such as occupation, income, and academic background were not related to early sexual debut age. In the 2006 male study, early sexual debut age was associated with occupation, income, and academic background. However, in the 2016 male study, participants' academic background was the only significant factor about early sexual debut age. In both the male and female studies, early sexual debut age was related to a higher number of sexual partners in life. Also, in both female cohorts (2004 and 2014), the number of pregnancies and the incidents of sexual abuse experienced were higher in the early sexual debut groups. CONCLUSIONS: Factors influencing early sexual debut were different in time and between men and women. And there was no significant association between SES factors and early sexual debut age in women. However, early sexual debut caused multiple problems, especially in young women. Thus, we need to create some suitable strategies to address these problems.

Efficacy and Safety of Mirodenafil Oro-Dispersible Film in Korean Patients with Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter, Phase IV Study.

PURPOSE: To investigate the efficacy, safety, and tolerability of oro-dispersible film (ODF) formulation of mirodenafil 50 mg and 100 mg for the treatment of patients with erectile dysfunction (ED) in Korea. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 129 subjects was performed. Subjects were randomized to either placebo or mirodenafil ODF 50 mg or 100 mg to be taken in an "on demand" manner for 8 weeks. The primary efficacy variable was the International Index of Erectile Dysfunction (IIEF)-5 questionnaire. The secondary efficacy variables comprised Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), the Global Assessment Question (GAQ), and the Life Satisfaction Checklist (LSC). RESULTS: IIEF-5 was significantly increased in all groups after treatment. However, compared to the placebo group, only the mirodenafil ODF 100 mg group showed a significant difference. SEP2 and SEP3 were increased in both mirodenafil groups; however, the increase was not statistically significant for SEP2. In terms of GAQ and LSC, the mirodenafil ODF groups showed significant increases compared with the baseline. Most treatment-associated adverse events were mild and resolved spontaneously. CONCLUSIONS: Mirodenafil ODF is an effective and well-tolerated agent for the treatment of patients with ED in Korea.

Free combination of dutasteride plus tamsulosin for the treatment of benign prostatic hyperplasia in South Korea: analysis of drug utilization and adverse events using the National Health Insurance Review and Assessment Service database.

OBJECTIVE: To assess the use and safety of free combination therapy (dutasteride and tamsulosin), dutasteride monotherapy, or tamsulosin monotherapy in patients with benign prostatic hyperplasia (BPH). METHODS: This non-interventional retrospective cohort study used claims data from the Korea Health Insurance Review and Assessment-National Patient Sample database. Patients with BPH ≥ 40 years of age receiving combination therapy (dutasteride 0.5 mg and tamsulosin 0.4 mg daily) or dutasteride 0.5 mg, or tamsulosin 0.4 mg daily dose between 2012 and 2017 were included. The frequency, duration of treatment and risk of any adverse event (AE) or serious AE (SAE) was compared for combination therapy versus each monotherapy using non-inferiority testing. RESULTS: Of 14,755 eligible patients, 1529 (10.4%) received combination therapy, 6660 (45.1%) dutasteride monotherapy, and 6566 (44.5%) tamsulosin monotherapy. The proportion of patients treated with combination therapy exceeded the pre-specified 3% threshold for 'frequent' use. Safety results indicated a similar risk of any AE and SAE irrespective of treatment group. The adjusted relative risk for any AE over the treatment observation period comparing combination therapy with dutasteride monotherapy was 1.07 (95% confidence interval [CI] 1.03, 1.12), and with tamsulosin monotherapy was 0.98 (95% CI 0.95, 1.02) demonstrating non-inferiority. The adjusted relative risk for any SAE was 1.07 (95% CI 0.66, 1.74) and 0.90 (95% CI 0.56, 1.45), compared with dutasteride and tamsulosin monotherapy, respectively. Although the SAE results did not statistically demonstrate non-inferiority of combination therapy based on pre-specified margins, the 95% CI for the risk ratio estimates included the null with a lower limit below the non-inferiority margins, indicating no meaningful differences in SAE risk between groups. Absolute SAE risks were low. CONCLUSION: Combination therapy with dutasteride and tamsulosin is frequently used in real-world practice in South Korea for treatment of BPH and demonstrates a safety profile similar to either monotherapy.

Intravesical Prostatic Protrusion and Prognosis of Non-Muscle Invasive Bladder Cancer: Analysis of Long-Term Data over 5 Years with Machine-Learning Algorithms.

We aim to investigate the significance of intravesical prostate protrusion (IPP) on the prognosis of non-muscle invasive bladder cancer (NMIBC) after the transurethral resection of bladder tumors (TURBT). For newly diagnosed NMIBC, we retrospectively analyzed the association between prognosis and IPP for at least a 5-year follow-up. A degree of IPP over 5 mm in a preoperative CT scan was classified as severe. The primary endpoint was recurrence-free survival, and the secondary endpoint was progression-free survival. The machine learning (ML) algorithm of a support vector machine was used for predictive model development. Of a total of 122 patients, ultimately, severe IPP was observed in 33 patients (27.0%). IPP correlated positively with age, BPH, recurrence, and prognosis. Severe IPP was significantly higher in the recurrence group and reduced in the recurrence-free survival group (p = 0.038, p = 0.032). Severe IPP independently increased the risk of intravesical recurrence by 2.6 times. The addition of IPP to the known oncological risk factors in the prediction model using the ML algorithm improved the predictability of cancer recurrence by approximately 6%, to 0.803. IPP was analyzed as a potential independent risk factor for NMIBC recurrence and progression after TURBT. This anatomical feature of the prostate could affect the recurrence of bladder tumors.

Lymphocyte-to-monocyte ratio is a predictor of clinically significant prostate cancer at prostate biopsy.

BACKGROUND: Inflammation plays critical roles at different stages of carcinogenesis and cancer progression. Several previous studies showed conflicting results for the predictive role of systemic inflammation markers in the detection of clinically significant prostate cancers (CSPCs). We aimed to determine the predictive roles of lymphocyte-to-monocyte (LMR) and eosinophil-to-lymphocyte ratios (ELR) in the detection of CSPC at standard 12-core transrectal ultrasound-guided prostate biopsy (12-core-TRUS-Bx) using our large-cohort database. METHODS: Clinical and pathological data of a total of 1740 men, who underwent initial standard 12-core TRUS-Bx, were analyzed. LMR and ELR were calculated from the prebiopsy complete blood count. Definitions of CSPC, LMR, and ELR were "Gleason grade group ≥2," "the lymphocyte counts/the monocyte counts," and "the eosinophil counts/the lymphocyte counts," respectively. RESULTS: Median (interquartile range) of serum prostate-specific antigen (PSA) level and prostatic volume before TRUS-Bx were 7.59 (5.02-13.12) ng/ml and 38.2 (29.0-52.9) ml, respectively. Benign prostatic lesions, clinically insignificant prostate cancers (CIPCs), and CSPCs were detected in 1179 (67.8%), 180 (10.3%), and 381 (21.9%) patients, respectively. The patients with CSPCs had older age, a higher prevalence of diabetes mellitus or hypertension, a higher rate of digital rectal examination abnormality, higher serum PSA level, lower serum testosterone level, and lower LMR than those with benign lesions or CIPCs. However, there was no difference in ELR among the three (benign lesions, CIPCs and CSPCs). In all the patients, multivariate regression analysis showed that lower LMR was an independent predictor of CSPCs compared with ELR. In the subset of men with prostate volume ≥39.3 ml, lower LMR was an independent predictor of CSPCs compared with ELR. In the subset of men with prostate volume <39.3 ml, men with lower LMR showed the tendency of having a higher probability of CSPCs without any statistical significance on the contrary to ELR. CONCLUSIONS: Our data indicate that LMR can play an independent predictive role in the detection of CSPCs at initial 12-core-TRUS-Bx compared with ELR. The predictive role of the LMR appears to be significant for men with larger prostate volume rather than those with smaller prostate volume.