Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

Purpose: Although the combination of androgen deprivation therapy with docetaxel or abiraterone acetate and prednisone has become a standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) and has shown improved overall survival, a subset of patients still progress to castration-resistant disease. However, the underlying molecular features in these patients remain poorly understood. Materials and Methods: We performed single-cell RNA sequencing (scRNA-seq) on 12 tissue samples, including 2 mHSPC samples, 7 primary prostate cancer (PCa) samples, and 3 matched normal samples from 7 patients. Raw sequencing data was processed by Cell Ranger software (10X Genomics) and aligned to the human reference genome (GRCh38). A comprehensive analysis of samples from patients with mHSPC was also conducted and validated using a cohort of 52 patients with mHSPC. Results: Our results identified distinct subpopulations within luminal and mononuclear phagocyte (MNP) clusters characterized by proliferative activation associated with unfavorable clinical outcomes. Furthermore, we observed that the MNP cluster exhibited significant proliferation activity. To understand the underlying mechanisms associated with aggressiveness, we conducted cell-cell interaction, copy number variation and pseudotime analysis. Utilizing 87 network genes from scRNA-seq, we classified 52 mHSPC patients into 2 molecular subtypes and demonstrated their correlation with distinct transcriptomic profiles and survival outcomes. Importantly, a 14-gene signature derived from 3 distinct gene sets exhibited a strong association with patient survival and drug response. The prognostic value of our findings was further validated in large-scale cohorts comprising localized PCa, metastatic PCa, mHSPC, and metastatic castration-resistant PCa patients. Conclusion This study provides valuable insights into the identification of high-risk patients, novel biomarkers, and potential therapeutic targets for individuals with mHSPC. Furthermore, the results in this study can serve as a basis for future investigations aimed at refining prognostic strategies and developing targeted therapies for patients with mHSPC.

Purpose: To evaluate whether extended pelvic lymph node dissection (PLND) improves survival outcomes compared with standard PLND in patients with bladder cancer (BCa) undergoing radical cystectomy (RC), and to assess its potential benefits in patients with prior or concurrent radical nephroureterectomy (p/cRNU). Materials and Methods: A multicenter analysis included 2202 patients with BCa undergoing RC with standard or extended PLND at 11 tertiary centers from 2003 to 2023. Following propensity score matching, 659 pairs (n=1,318), including 128 patients with p/cRNU, were analyzed. Recurrence-free survival (RFS) was the primary outcome, while overall survival (OS), cancer-specific survival (CSS), and readmission rates were secondary outcomes. Survival analyses performed using Kaplan-Meier methods and clustered Cox models. Results: Extended PLND yielded significantly more lymph nodes than standard PLND (median: 27.0 vs. 17.0, p<0.001) but did not improve RFS, CSS, or OS in the overall cohort (all p>0.05). Extended PLND increased readmission rates (28.4% vs. 20.2%, p=0.001) and readmission risk (odds ratio, 1.57; 95% confidence interval [CI], 1.15–2.16, p=0.005). However, subgroup analysis revealed extended PLND significantly improved RFS in patients with p/cRNU (hazard ratio, 0.54; 95% CI, 0.38–0.77; p<0.001). Conclusion Extended PLND does not provide survival benefits for overall patient population and increases readmission risk but significantly improves RFS in patients with p/cRNU. Tailoring PLND extent based on upper tract disease status is recommended.

Purpose: This study aimed to evaluate the effectiveness of intraoperative Guardix-SG application in reducing postoperative ileus (POI) and preventing adhesive small bowel obstruction (SBO) following radical cystectomy (RC) for bladder cancer. Materials and Methods: A single-arm, prospective observational study was conducted from April 2022 to February 2025. Sixty-seven patients undergoing RC with pelvic lymph node dissection received intraoperative Guardix-SG application after urinary reconstruction. Patients with prior abdominal surgery or pelvic radiotherapy were excluded. POI was defined as (1) the absence of flatus or stool by postoperative day (POD) 6 (definition 1) or (2) intolerance to oral intake by POD 5 requiring nasogastric decompression or intravenous support (definition 2). Adhesive SBO was defined as radiologic or clinical bowel obstruction without a mechanical cause. Outcomes were monitored for 3 months. Predictors of POI (definition 2) were identified using multivariable logistic regression. Results: The median age was 69.0 (interquartile range, 62.5–75.0) years, and 88.1% of participants were male. Robot-assisted surgery was performed in 62.7% of cases, and ileal conduit diversion was most common (64.2%). The incidence of POI was 3.0% (2 of 67) by definition 1 and 19.4% (13/67) by definition 2. Nasogastric tube placement was required in 6.0% (4 of 67). No cases of adhesive SBO or gastrointestinal reoperation were observed. Multivariable analysis identified lower body mass index as an independent predictor of POI (odds ratio, 0.74; 95% confidence interval, 0.57–0.96; p=0.023). No significant associations were found with surgical approach, diversion type, or operative time. Compared with previous studies reporting SBO rates of 3%–5% and POI rates of 14%–27%, the observed complication rates were lower or comparable. Conclusion Intraoperative Guardix-SG application resulted in favorable bowel outcomes after radical cystectomy, with no observed SBO and a reduced incidence of POI.

This study aimed to assess the prognostic role of body mass index (BMI) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line immune checkpoint inhibitor (ICI)-based therapy. We searched for relevant studies in the MEDLINE, Embase, and Cochrane Library databases. The initial search yielded 599 records, of which seven articles (2,517 patients) were selected for analysis. Patients with a high BMI had a favorable overall survival (OS) based on hazard ratio (HR) (crude HR 0.69, 95% confidence interval [CI] 0.57–0.83, p<0.0001; adjusted (a)HR 0.75, 95% CI 0.59–0.95, p=0.02), but not relative risk (RR 0.88, 95% CI 0.67–1.16, p=0.37). In the subgroup analysis, patients with a high BMI had better OS in the ICI with tyrosine kinase inhibitor (TKI) subgroup (aHR 0.71, 95% CI 0.55–0.92, p=0.01), while no significant difference was found in the ICI-only subgroup (aHR 1.02, 95% CI 0.56–1.87, p=0.95). Adjusted statistics for progression-free survival (PFS) were assessable in predominantly ICI-only studies and demonstrated a favorable outcome for patients with a low BMI (aHR 1.67, 95% CI 1.14–2.45, p=0.01). In conclusion, the impact of high BMI varies depending on the treatment type, exhibiting a favorable correlation with OS within ICI with TKI subgroup, but indicating an adverse association with PFS in the ICI-only subgroup. Further research is needed to clarify the influence of BMI by stratifying patients into ICI-only and ICI with TKI treatment to provide more insights.

Purpose: We compared success rates of 3 surgical techniques (holmium laser enucleation of the prostate [HoLEP], transurethral resection of the prostate [TURP], and photoselective laser vaporization prostatectomy [PVP]) for treatment of benign prostatic obstruction (BPO). We aimed to identify preoperative clinical variables and urodynamic parameters that predict surgical success. Methods: A total of 483 patients who underwent surgical treatment for BPO at Samsung Medical Center between 2006 and 2017 were retrospectively analyzed; of these 361, 81, and 41 patients underwent HoLEP, TURP, and PVP, respectively. Prostate-specific antigen, prostate volume, urodynamic parameters, and International Prostate Symptom Score (IPSS)/quality of life (QoL) index were evaluated preoperatively; uroflowmetry, postvoid residual urine, and IPSS/QoL index were measured 6 months postoperatively. Surgical success was defined based on IPSS, maximum flow rate, and QoL index and predictive factors were identified using multiple logistic regression analyses. Results: Success rates of HoLEP, TURP, and PVP were 67.6%, 65.4%, and 34.1%, respectively, and the HoLEP and TURP groups were not significantly different. Regression analysis revealed prostate volume ≥50 mL and bladder outlet obstruction index (BOOI) ≥40 to be independent factors predicting HoLEP success. Only high preoperative QoL could predict the success of TURP, whereas other urodynamic parameters remained unrelated. Conclusions Patients treated with HoLEP and TURP displayed equivalent efficacies, but PVP was relatively less efficient than both. Preoperative variables of prostate volume ≥50 mL and BOOI ≥40 were independent predictive factors for the success of HoLEP but not of TURP.

Purpose: We compared success rates of 3 surgical techniques (holmium laser enucleation of the prostate [HoLEP], transurethral resection of the prostate [TURP], and photoselective laser vaporization prostatectomy [PVP]) for treatment of benign prostatic obstruction (BPO). We aimed to identify preoperative clinical variables and urodynamic parameters that predict surgical success. Methods: A total of 483 patients who underwent surgical treatment for BPO at Samsung Medical Center between 2006 and 2017 were retrospectively analyzed; of these 361, 81, and 41 patients underwent HoLEP, TURP, and PVP, respectively. Prostate-specific antigen, prostate volume, urodynamic parameters, and International Prostate Symptom Score (IPSS)/quality of life (QoL) index were evaluated preoperatively; uroflowmetry, postvoid residual urine, and IPSS/QoL index were measured 6 months postoperatively. Surgical success was defined based on IPSS, maximum flow rate, and QoL index and predictive factors were identified using multiple logistic regression analyses. Results: Success rates of HoLEP, TURP, and PVP were 67.6%, 65.4%, and 34.1%, respectively, and the HoLEP and TURP groups were not significantly different. Regression analysis revealed prostate volume ≥50 mL and bladder outlet obstruction index (BOOI) ≥40 to be independent factors predicting HoLEP success. Only high preoperative QoL could predict the success of TURP, whereas other urodynamic parameters remained unrelated. Conclusions Patients treated with HoLEP and TURP displayed equivalent efficacies, but PVP was relatively less efficient than both. Preoperative variables of prostate volume ≥50 mL and BOOI ≥40 were independent predictive factors for the success of HoLEP but not of TURP.

Background: To evaluate the strategy for detection of prostate cancer (PCa) with low prostate specific antigen (PSA) level (2.5–4.0 ng/mL), prostate biopsy patients with low PSA were assessed. We evaluated the risk of low PSA PCa and the strategy for screening low-PSA patients. Methods: We retrospectively analyzed the patients who underwent prostate biopsy with low PSA level. Baseline characteristics, PSA level before prostate biopsy, prostate volume, prostate specific antigen density (PSAD), and pathological data were assessed. Results: Among the 1986 patients, 24.97% were diagnosed with PCa. The PSAD was 0.12 ± 0.04 ng/mL2 in the PCa-diagnosed group and 0.10 ± 0.04 ng/mL2 in non-cancer-diagnosed group (P < 0.001). Of the 496 patients diagnosed with PCa, 302 (60.89%) were in the intermediate- or high-risk group. PSAD was 0.13 ± 0.04 ng/mL2 in the intermediate- or highrisk group and 0.11 ± 0.03 ng/mL2 in the very low- and low-risk group (P < 0.001). Of 330 patients who underwent radical prostatectomy, 85.15% were diagnosed as having significant cancer. There was significant correlation between PSAD and PCa (r = 0.294, P < 0.001).PSAD with a specificity of 80.00% of a clinically significant cancer diagnosis was assessed at 0.1226 ng/mL2 . Conclusion The PCa detection rate in the low-PSA group was not lower than that of previous studies of patients with PSA from 4.0 to 10.0 ng/mL. Further, it may be helpful to define a strategy for PCa detection using PSAD in the low-PSA group.

PURPOSE: The current study is aimed to assess whether a longer duration of 5α-reductase inhibitor (5α-RI) exposure was associated with higher rate of permanent erectile dysfunction (ED) in a rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats (n=76) were assigned to five groups: (i) normal control group; (ii) dutasteride (0.5 mg/rat/d) for 4-weeks group; (iii) dutasteride for 4-weeks plus 2-weeks of resting group; (iv) dutasteride for 8-weeks group; and (v) dutasteride for 8-weeks plus 2-weeks of resting group. In vivo erectile responses to electrical stimulation, and changes of fibrotic factors and smooth muscle/collagen contents in the corpus cavernosum were evaluated in each group. RESULTS: Dutasteride administration for 4 and 8 weeks significantly decreased erectile parameters compared with the control group. Reduced erectile responses were recovered during 2 weeks of drug-free time in the 4-week treatment group, but were not in the 8-week group. Protein levels of fibrosis-related factors transforming growth factor (TGF)-β1, TGF-β2, and p-Smad/Smad (Smad 2/3) in the corpus cavernosum showed no significant change after 4 weeks of dutasteride oral administration, but were enhanced after 8 weeks. Dutasteride markedly decreased smooth muscle content and increased collagen after 4 and 8 weeks of use, but no nuclear size changes; however, neither group showed significant improvement in the smooth muscle to collagen ratio after the rest period. CONCLUSIONS: Our study showed that recovery from ED depended on the duration of medication, and administration of dutasteride for more than 8-weeks in rats could result in irreversible ED even after discontinuation of medication.
5-alpha Reductase Inhibitors ; Administration, Oral ; Animals ; Collagen ; Dutasteride ; Electric Stimulation ; Erectile Dysfunction ; Finasteride ; Humans ; Male ; Models, Animal ; Muscle, Smooth ; Oxidoreductases ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factors