Purpose: To assess the effectiveness of the prostate health index (PHI) in patients with no index lesions on multiparametric magnetic resonance imaging (mpMRI) or with negative findings on past prostate biopsy if there was an index lesion on mpMRI. Materials and Methods: Patients without an index lesion on MRI or with a negative result on combined biopsy for index lesions were assessed. Patients who underwent transperineal mapping biopsy among those suspected of having prostate cancer (PCa) due to persistently elevated prostate-specific antigen (PSA) levels were analyzed. Results: Of the 291 patients, 82 (28.2%) were diagnosed with PCa. Sixty-five of 291 patients had negative finding in previous combined biopsy. In total, 226 patients did not have any index lesions. The mean age of the PCa group was 64.33±8.88 years and that of the non-cancer group was 59.88±10.26 years (p<0.001). The PHI was 46.75±28.22 in the PCa group and 37.74±17.37 in the noncancer group (p=0.001), and the prostate volume was 41.52±15.77 mL in the PCa group and 50.78±23.97 mL in the non-cancer group (p=0.001). In multivariate analysis, age (odds ratio [OR] 1.096, p<0.001), PHI (OR 1.021, p=0.005), and prostate volume (OR 0.954, p<0.001) were identified as significant factors for PCa detection. The optimal cutoff value of the PHI for PCa detection was 44.6 and the PHI density (PHID) was 0.88. Conclusions In patients with elevated PSA levels but no index lesions on mpMRI or negative biopsy findings, PHI and PHID demonstrated significant potential for improving PCa detection.

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.

Purpose: We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. Materials and Methods: Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy. Results: Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence. Conclusion This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: This study assessed the comparative effectiveness of sextant and extended 12-core systematic biopsy within combined biopsy for the detection of prostate cancer. Methods: Patients who underwent combined biopsy targeting lesions with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3–5 were assessed. Two specialists performed all combined cognitive biopsies. Both specialists performed target biopsies with five or more cores. One performed sextant systematic biopsies, and the other performed extended 12-core systematic biopsies. A total of 550 patients were analyzed. Results: Cases requiring systematic biopsy in combined biopsy exhibited a significant association with age ≥ 65 years (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.25– 4.32; P = 0.008), PI-RADS score (OR, 2.32; 95% CI, 1.25–4.32; P = 0.008), and the number of systematic biopsy cores (OR, 3.69; 95% CI, 2.11–6.44; P < 0.001). In patients with an index lesion of PI-RADS 4, an extended 12-core systematic biopsy was required (target-negative/ systematic-positive or a greater Gleason score in the systematic biopsy than in the targeted biopsy) (P < 0.001). Conclusion During combined biopsy for prostate cancer in patients with PI-RADS 3 or 5, sextant systematic biopsy should be recommended over extended 12-core systematic biopsy when an effective targeted biopsy is performed.

Purpose: Giant cell tumor (GCT) of the proximal femur is relatively rare, with only a few case series reported thus far. This study aimed to evaluate the clinical outcomes of GCT of the proximal femur treated with intralesional curettage and expand the understanding of their characteristics and treatment considerations. Materials and Methods: Fifteen cases treated with curettage for GCT of the proximal femur between 2007 and 2020 were reviewed. The median follow-up was 46 months (25–150 months). There were 10 males and 5 females with a median age of 26 years (17–71 years). After curettage, the bone defect was filled with either an allograft (7 cases) or bone cement (8 cases). Results: The postoperative complications were local recurrences in three cases (20.0%), including malignant transformation in one case and a femur neck fracture in one case (6.7%) following curettage and strut allograft. Among the 15 cases, 13 (86.7%) retained their native joint at the last follow-up. No patients developed degenerative changes or osteonecrosis. Conclusion The results of proximal femoral GCT with curettage were acceptable despite local recurrences in three cases (20.0%), and femur neck fracture in one case. An appropriate surgical approach and reconstruction according to the extent of the lesion are necessary for successful treatment.

Purpose: To assess the feasibility and short-term efficacy of maintenance enzalutamide following first-line docetaxel plus androgen deprivation therapy (ADT) in patients with high-volume, metastatic castration-naive prostate cancer (mCNPC). Materials and Methods: The present study included 38 consecutive patients with mCNPC who did not have disease progression with ADT plus docetaxel between October 2022 and October 2023. Patients received a switch maintenance therapy with enzalutamide until progression, unacceptable toxicity, or patient withdrawal. Endpoints included time to prostate-specific antigen (PSA) progression and safety. Results: Among the 38 patients, the median age was 68 years, and the most frequently observed metastatic site was bone (n=36), followed by lymph nodes (n=28), lung (n=8), and liver (n=1). The median duration of firstline docetaxel was 2.8 months (range, 2.7–5.0 months). At the time of commencing maintenance enzalutamide, the median PSA was 3.2 ng/mL (range, 0.01–258 ng/mL). Maintenance enzalutamide was generally welltolerated. A total of 11 patients (28%) discontinued enzalutamide, and the main reasons included adverse events (prolonged fatigue of grade 1 or 2, n=6), disease progression (n=3) and financial burdens (n=2). Median time to PSA progression was not reached, and 93% were PSA progression-free at 12 months. Conclusions Maintenance enzalutamide is a feasible treatment option with potential clinical benefit for patients with high-volume mCNPC who were progression-free after first-line ADT+docetaxel.

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multipotent protein that plays essential roles in cellular responses to oxidative stress. Methods: To examine the role of APE1/Ref-1 in ischemia-reperfusion (I/R) injuries and hydrogen peroxide (H2O2)-induced renal tubular apoptosis, we studied male C57BL6 mice and human proximal tubular epithelial (HK-2) cells treated with H2O2 at different concentrations. The colocalization of APE1/Ref-1 in the proximal tubule, distal tubule, thick ascending limb, and collecting duct was observed with confocal microscopy. The overexpression of APE1/Ref-1 with knockdown cell lines using an APE1/Ref-1–specific DNA or small interfering RNA (siRNA) was used for the apoptosis assay. The promotor activity of nuclear factor kappa B (NF-κB) was assessed and electrophoretic mobility shift assay was conducted. Results: APE1/Ref-1 was predominantly localized to the renal tubule nucleus. In renal I/R injuries, the levels of APE1/Ref-1 protein were increased compared with those in kidneys subjected to sham operations. The overexpression of APE1/Ref-1 in HK-2 cells enhanced the Bax/Bcl-2 ratio as a marker of apoptosis. Conversely, the suppression of APE1/Ref-1 expression by siRNA in 1-mM H2O2-treated HK-2 cells decreased the Bax/Bcl-2 ratio, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and NF-κB. In HK-2 cells, the promoter activity of NF-κB increased following H2O2 exposure, and this effect was further enhanced by APE1/Ref-1 transfection. Conclusion: The inhibition of APE1/Ref-1 with siRNA attenuated H2O2-induced apoptosis through the modulation of mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 and the nuclear activation of NF-κB and proapoptotic factors.