Integrated Bioinformatics Analysis Identified ASNS and DDIT3 as the Therapeutic Target in Castrate-Resistant Prostate Cancer.

Many studies have demonstrated the mechanisms of progression to castration-resistant prostate cancer (CRPC) and novel strategies for its treatment. Despite these advances, the molecular mechanisms underlying the progression to CRPC remain unclear, and currently, no effective treatments for CRPC are available. Here, we characterized the key genes involved in CRPC progression to gain insight into potential therapeutic targets. Bicalutamide-resistant prostate cancer cells derived from LNCaP were generated and named Bical R. RNA sequencing was used to identify differentially expressed genes (DEGs) between LNCaP and Bical R. In total, 631 DEGs (302 upregulated genes and 329 downregulated genes) were identified. The Cytohubba plug-in in Cytoscape was used to identify seven hub genes (ASNS, AGT, ATF3, ATF4, DDIT3, EFNA5, and VEGFA) associated with CRPC progression. Among these hub genes, ASNS and DDIT3 were markedly upregulated in CRPC cell lines and CRPC patient samples. The patients with high expression of ASNS and DDIT3 showed worse disease-free survival in patients with The Cancer Genome Atlas (TCGA)-prostate adenocarcinoma (PRAD) datasets. Our study revealed a potential association between ASNS and DDIT3 and the progression to CRPC. These results may contribute to the development of potential therapeutic targets and mechanisms underlying CRPC progression, aiming to improve clinical efficacy in CRPC treatment.

Non-Invasive Radiofrequency Hyperthermia Attenuates HMGB1/TLR4/NF-κB Inflammatory Axis in a Chronic Prostatitis/Chronic Pelvic Pain Syndrome Rat Model.

PURPOSE: The primary goal of this study is to evaluate the effect of the non-invasive radiofrequency hyperthermia (RFHT) device on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) rat model and investigate the underlying mechanism. MATERIALS AND METHODS: In this study, Sprague-Dawley rats were randomly distributed into three groups: (1) normal control group, (2) CP/CPPS group, and (3) RFHT group. CP/CPPS rat models were induced by 17ß-estradiol and dihydrotestosterone for 4 weeks and RFHT was administered for 5 weeks after model establishment. During RFHT administration, core body temperatures were continuously monitored with a rectal probe. After administering RFHT, we assessed pain index for all groups and collected prostate tissues for Western blot analysis, immunofluorescence, and immunohistochemistry. We also collected adjacent organs to the prostate including urinary bladder, testes, and rectum for safety assessment via H&E staining along with a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. RESULTS: After administering RFHT, pain in rats was significantly alleviated compared to the CP/CPPS group. RFHT reduced high-mobility group box 1 (HMGB1) expression and improved inflammation by downregulating subsequent proinflammatory cytokines through inhibition of the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. In prostate-adjacent organs, no significant histological alteration or inflammatory infiltration was detected. The area of cell death also did not increase significantly after RFHT. CONCLUSIONS: In conclusion, RFHT demonstrated anti-inflammatory effects by inhibiting the HMGB1-TLR4-NF-κB pathway in CP/CPPS rat models. This suggests that RFHT could serve as a safe and promising therapeutic strategy for CP/CPPS.

Safety and Efficacy Assessment of Red Ginseng Oil (RXGIN) in Men with Lower Urinary Tract Symptoms in a Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of red ginseng oil (RXGIN) in men with lower urinary tract symptoms. MATERIALS AND METHODS: Men aged between 40 and 75 years with a total International Prostate Symptom Score (IPSS) of 8 to 19 points were recruited from April 2020 to December 2020. Subjects were randomly assigned to either the RXGIN group or the control group in a 1:1 ratio and received either RXGIN or placebo daily for 12 weeks. For the primary outcome, changes in IPSS scores at 6 and 12 weeks from baseline were analyzed. The secondary outcomes were changes in International Index of Erectile Function (IIEF), maximum urinary flow rate, and post-void residual volume at weeks 6 and 12 compared to baseline. Urine analysis and blood tests were additionally performed for safety assessment. RESULTS: A total of 88 subjects (RXGIN group, 46; control group, 42) completed the study. The total IPSS and IPSS subscores (residual urine sensation, frequency, intermittency, urgency, weak stream, straining, nocturia, and quality of life) were significantly improved in the RXGIN group compared to the control group at weeks 6 and 12. Total IIEF and sexual desire were significantly improved in the RXGIN group at week 6 and week 12, respectively, but there were no significant changes in the level of serum testosterone or dihydrotestosterone. The serum prostate-specific antigen showed significant decrease at weeks 12. No serious adverse events leading to discontinuation of the study drug were observed in the RXGIN group. CONCLUSIONS: Red ginseng oil (RXGIN) appears to be safe and effective in improving lower urinary tract symptoms in men and may also improve some aspects of sexual function.

Retroperitoneal Single-Port Robot-Assisted Nephroureterectomy with Bladder Cuff Excision: Initial Experience and Description of the Technique.

BACKGROUND: With the introduction of the single-port (SP) robot, surgery that was difficult to attempt is becoming possible. Nephroureterectomy (NUx) for upper tract urothelial carcinoma also seems to be able to attempt a retroperitoneal (RP) approach. PURPOSE: to investigate the feasibility of SP robotic RP NUx with bladder cuff excision. DESIGN, SETTING, AND PARTICIPANTS: we sequentially analyzed 20 patients who underwent SP robot NUx from January 2021 to December 2022. SURGICAL PROCEDURE: all patients were diagnosed with upper tract urothelial carcinoma (UTUC) and were operated upon by a single expert using the da Vinci SP platform (Intuitive Surgical, Sunnyvale, CA, USA) with retroperitoneal approach. RESULTS AND LIMITATIONS: A total of 20 patients underwent SP robotic NUx with bladder cuff excision. The mean age of patients was 69.45 ± 8.68 years, and the mean body mass index (BMI) was 25.37 ± 3.00 kg/m2. The mean tumor size was 2.42 ± 1.03 cm on a CT scan, with right-sided tumors in eight patients (40%) and left-sided tumors in 12 patients (60%). The median console time was 106 min and 40 s, and the expected blood loss was 122.50 ± 75.18 mL. Final pathology showed that all of the patients were diagnosed as having urothelial carcinoma; one patient was classified as Ta (5.00%), three patients were classified as T1 (15.00%), seven patients were classified as T2 (35.00%), eight patients were classified as T3 (40.00%), and one patient was classified as T4 (5.00%). None of these 20 patients showed any complications based on the Clavien-Dindo scale. CONCLUSIONS: SP robotic NUx using a retroperitoneal approach provides feasible perioperative and postoperative outcomes for UTUC.

Urethra-Sparing Robot-Assisted Simple Prostatectomy for Postoperative Antegrade Ejaculation.

BACKGROUND: We report a comparative analysis of extraperitoneal urethra-sparing robot-assisted simple prostatectomy (EUS-RASP) versus robot-assisted simple prostatectomy (RASP) using the Freyer approach for patients with a large prostate volume greater than 80 mL. METHODS: A total of 32 patients underwent EUS-RASP, and 30 underwent RASP from April 2018 to November 2021. All the perioperative data and 6-month follow-up data were collected prospectively. We retrospectively evaluated baseline characteristics and functional outcomes, including International Prostate Symptom Scores (IPSSs) and quality of life (QOL), maximum flow rate, and post-void residual volume, between the two groups. Sexual function was analyzed in the EUS-RASP group. RESULTS: The patients undergoing EUS-RASP and RASP had comparable baseline characteristics and functional outcomes. The EUS-RASP group showed a shorter operative time (123.4 ± 15.2 min vs. 133.7 ± 21.4 min, p = 0.034), length of hospital stay (2.9 ± 1.5 days vs. 4.6 ± 1.5 days, p = 0.001), and catheterization time (2.4 ± 1.7 days vs. 8.1 ± 2.4 days, p < 0.001). A total of 14/32 (43.8%) patients reported normal preoperative ejaculatory function in the EUS-RASP group, and 11/14 (78.6%) maintained antegrade ejaculation postoperatively. CONCLUSIONS: Extraperitoneal urethra-sparing RASP is an effective and feasible procedure that can improve voiding function and allow for the maintenance of ejaculatory function in patients with large prostates.

Comparing 12-core and 20-core biopsy for prostate cancer diagnosis with transperineal MR/US fusion biopsy: assessing the effective number of systemic cores using propensity score matching.

PURPOSE: For transperineal (TP) prostate biopsy, target biopsy for visible lesions on MRI is important, but there is no consensus of the number of systemic biopsy cores. Our study aimed to confirm the diagnostic efficiency of 20-core systemic biopsy by comparison with 12-core using propensity score matching (PSM). METHODS: The 494 patients conducted the naive TP biopsy were retrospectively analyzed. There were 293 patients with 12-core biopsy and 201 patients with 20-core biopsy. PSM was performed for minimizing confounding variables, and the established effects' value was analyzed for 'index-positive or negative' clinically significant prostate cancer (csPCa) (Index means PIRADS Score ≥ 3 on multiparametric prostate MRI). RESULTS: At 12-core biopsy, there were 126 cases of prostate cancer (43.0%), and 97 cases of csPCa (33.1%). At 20-core biopsy, there were 91 cases (45.3%) and 63 cases (31.3%). After propensity score matching, for index-negative csPCa, the estimated odds ratio was 4.03 (95% CI 1.35-12.09, p value 0.0128), and for index-positive csPCa, the estimated odds ratio was 0.98 (95% CI 0.63-1.52, p value 0.9308). CONCLUSIONS: The 20-core biopsy did not show a higher detection rate for csPCa in comparison with the 12-core biopsy. However, when MRI did not show a suspicious lesion, 20-core biopsy showed higher odd ratio in comparison with 12-core biopsy. Therefore, if there is a suspicious lesion in MRI, 20-core biopsy is excessive and 12-core biopsy is sufficient. Whereas if there is no suspicious lesion in MRI, it is better to proceed with 20-core biopsy.

Longitudinal Analyses of Mutational Subclonal Architecture and Tumor Subtypes in Recurrent Bladder Cancer.

Longitudinal tumor sequencing of recurrent bladder cancer (BC) can facilitate the investigation of BC progression-associated genomic and transcriptomic alterations. In this study, we analyzed 18 tumor specimens including distant and locoregional metastases obtained during tumor progression for five BC patients using whole-exome and transcriptome sequencing. Along with the substantial level of intratumoral mutational heterogeneity across the cases, we observed that clonal mutations were enriched with known BC driver genes and apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC)-associated mutation signatures compared with subclonal mutations, suggesting the genetic makeup for BC tumorigenesis associated with APOBEC deaminase activity was accomplished early in the cancer evolution. Mutation-based phylogenetic analyses also revealed temporal dynamics of mutational clonal architectures in which the number of mutational clones varied along the BC progression and notably was often punctuated by clonal sweeps associated with chemotherapy. The bulk-level transcriptome sequencing revealed frequent subtype switching in which transcriptionally defined BC subtypes may vary during tumor progression. Longitudinal whole-exome and transcriptome sequencing of recurrent BC may advance our understanding into the BC heterogeneity in terms of somatic mutations, cell clones and transcriptome-based tumor subtypes during disease progression.

Optimal sequencing of the first- and second-line target therapies in metastatic renal cell carcinoma: based on nationally representative data analysis from the Korean National Health Insurance System.

BACKGROUND: The authors intend to compare the effects of each targeted therapy (TT) in the treatment of patients with metastatic renal cell carcinoma (mRCC) using big data based on the Korean National Health Insurance System (NHIS) and determine the optimal treatment sequence. METHODS: Data on the medical use of patients with kidney cancer were obtained from the NHIS database from January 1, 2002, to December 31, 2020. Patient variables included age, sex, income level, place of residence, prescribing department, and duration from diagnosis to the prescription date. The primary outcome was overall survival (OS) for each drug and sequencing. We performed propensity score matching (PSM) according to age, sex, and Charlson Comorbidity Index based on the primary TTs. RESULTS: After 1:1 PSM, the sunitinib (SUN) (n = 1,214) and pazopanib (PAZ) (n = 1,214) groups showed a well-matched distribution across the entire cohort. In the primary treatment group, PAZ had lower OS than SUN (HR, 1.167; p = 0.0015). In the secondary treatment group, axitinib (AXI) had more favorable OS than cabozantinib (CAB) (HR, 0.735; p = 0.0118), and everolimus had more adverse outcomes than CAB (HR, 1.544; p < 0.0001). In the first to second TT sequencing, SUN-AXI had the highest OS; however, there was no statistically significant difference when compared with PAZ-AXI, which was the second highest (HR, 0.876; p = 0.3312). The 5-year survival rate was calculated in the following order: SUN-AXI (51.44%), PAZ-AXI (47.12%), SUN-CAB (43.59%), and PAZ-CAB (34.28%). When the four sequencing methods were compared, only SUN-AXI versus PAZ-CAB (p = 0.003) and PAZ-AXI versus PAZ-CAB (p = 0.017) were statistically significant. CONCLUSIONS: In a population-based RWD analysis of Korean patients with mRCC, SUN-AXI sequencing was shown to be the most effective among the first to second TT sequencing methods in treatment, with a relative survival advantage over other sequencing combinations. To further support the results of this study, risk-stratified analysis is needed.

Irreversible electroporation for prostate cancer using PSMA PET-CT.

Background: To demonstrate the clinical usefulness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computerized tomography (CT) for irreversible electroporation (IRE) in prostate cancer patients. Methods: From January to May 2021, 17 men were diagnosed with localized prostate cancer through preoperative mpMRI and [18F] florastamin PSMA PET-CT imaging, followed by transperineal MRI-ultrasound fusion-guided biopsy. The patients underwent IRE focal therapy at the target lesions under general anesthesia. To evaluate the treatment outcome, serum prostate-specific antigen (PSA) levels were followed up in the 1st, 3rd, 6th, 9th, 12th months, and mpMRI was taken in the 1st and 12th months, followed by MR fusion biopsy in the 12th month post-IRE. Results: The mean age of the patients was 66.1 ± 9.3 with a median PSA of 7.5 ng/ml. After the treatment, PSA nadir was 4.06 ± 3.4, and 11 (64.7%) achieved decline of PSA more than 50% from the baseline. Rate of negative biopsy for prostate cancer is 88% (15/17) at 12 months MR fusion biopsy after the IRE treatment. Among the relapsed cases, 1 (6.9%) patient recurred at margin of treated area, and 1 (6.9%) patient was from outfield recurrence. When excluding initial four patients, none of the patients had cancer recur. Conclusions: When treating with IRE focal therapy, PSMA-PET CT is a potentially valuable diagnostic approach for localizing prostate cancer; it supports the detection of lesions with conventional mpMRI, enabling to perform the procedure more completely.

Comparison of Transperitoneal and Retroperitoneal Partial Nephrectomy with Single-Port Robot.

Purpose: To investigate the efficacy and safety of single-port (SP) robotic transperitoneal (TP) and retroperitoneal (RP) partial nephrectomy. Materials and Methods: We sequentially analyzed 30 partial nephrectomy performed after the SP robot was introduced to the hospital in September 2021 to June 2022. All patients were found to have T1 renal cell carcinoma (RCCs) and were operated by a single expert in conventional robot with da Vinci SP platform. Results: Total of 30 patients underwent SP robotic partial nephrectomy with 16 (53.33%) by TP approach and 14 (47.67%) by RP. Body mass index was slightly higher in TP group (25.37 vs 23.53, p-value = 0.040). The other demographic information was not significantly different. There was no statistical difference in ischemic time (727.41 ± 561.18 seconds for TP and 698.56 ± 299.23 seconds for RP, p-value = 0.812), and console time (67.97 ± 24.06 minutes for TP and 69.71 ± 28.66 minutes for RP, p-value = 0.724). There was no statistical difference in perioperative and pathologic outcomes either. Postoperative renal function calculated from diethylenetriaminepentacetate was 103.33 mL/min/1.73 m2 for TP and 101.33 mL/min/1.73 m2 for RP (p-value = 0.214). And 90.36 mL/min/1.73 m2 for TP and 87.74 mL/min/1.73 m2 for RP at 90 days after surgery (p-value = 0.592). Conclusion: SP robot partial nephrectomy can be performed effectively and safely regardless of the approach. TP and RP approach offers similar perioperative and postoperative outcomes for T1 RCC. The Clinical Trial Registration number KC22WISI0431.

Quisqualis indica extract for men with lower urinary tract symptoms: A randomized, double-blind, placebo-controlled trial.

PURPOSE: To evaluate the efficacy and safety of Quisqualis indica in men with moderate lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 135 subjects with International Prostate Symptom Score (IPSS) of 8-19 were randomized in 2 centers from June 2018 to April 2019. Patients were assigned into one of the three groups: a low-dose group (LG, 1,000 mg Q. indica), a high-dose group (HG, 2,000 mg Q. indica) or a placebo group (PG). The primary endpoint was the change of IPSS at the end of treatment from baseline. Secondary end points included the changes of prostate specific antigen, testosterone, dihydrotestosterone, maximum urinary flow rate (Qmax), postvoid residual volume (PVR) and International Index of Erectile Function-5 (IIEF-5), with drug safety. RESULTS: 113 patients were able to finish the study. Compared to the PG, total IPSS in the LG and the HG was significantly improved at 6 weeks and 12 weeks. For IPSS subscores, LG showed improvements in all except for urgency and quality of life at 6 weeks. HG showed improvements in incomplete emptying and frequency at 6 weeks and 12 weeks along with improvements in intermittency, straining, and quality of life at 12 weeks. For IIEF-5 subscores, orgasmic function and overall satisfaction improved in HG when compared to PG at 12 weeks. Lastly, increase of Qmax and decrease of PVR was observed at 6 weeks in LG. CONCLUSIONS: 12-week treatment with Q. indica has a therapeutic effect and is well tolerated in patients with LUTS.

Combined MRI and PSA Strategy Improves Biopsy Decisions Compared with PSA Only: Longitudinal Observations of a Cohort of Patients with a PSA Level Less Than 20 ng/mL.

RATIONALE AND OBJECTIVES: To assess the diagnostic performances of prostate specific antigen (PSA) and PSA with prostate magnetic resonance imaging (MRI) to predict prostate cancer in patients with PSA ≤ 20 ng/mL. MATERIALS AND METHODS: Patients suspected of prostate cancer with a PSA test and prebiopsy MRI were included (n = 881). Prostate biopsy results or follow-up clinical data for 2 years were used to determine the presence of prostate cancer. The diagnostic performance of PSA, MRI, and PSA with MRI (referred to as the protocol) was evaluated. The positive predictive value (PPV) and negative predictive value (NPV) of the MRI were calculated in subgroups of patients with specific ranges of PSA level. RESULTS: Prostate cancer and CSC were diagnosed in 220 and 162 patients, respectively. Adding MRI to PSA could greatly improve specificity and PPV (0.833 and 0.567) for detecting CSC, compared to PSA ≥ 4 ng/mL alone (0.248 and 0.0219). Even though the sensitivity of the protocol (0.679) was lower than PSA (0.938), the NPV of the protocol was comparable to PSA (0.929 vs. 0.924). The protocol consistently showed the superior PPV and NVP to PSA only in not only patients within the gray zone of PSA, but also in patients with higher PSA. CONCLUSION: In conclusion, this longitudinal observational study confirmed that adding prebiopsy MRI to PSA was consistently beneficial in patients with PSA ≤ 20 ng/mL for avoiding unnecessary biopsy despite decrease in the sensitivity.

Longitudinal Transcription Profiling of Bladder Cancers Dictate the Response to BCG Treatment and Disease Progression.

Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients.

Cervi Parvum Cornu complex for men with lower urinary tract symptoms: a multicenter, randomized, double-blind, placebo-controlled trial.

Background: To evaluate the efficacy and safety of Cervi Parvum Cornu, Angelicae Gigantis Radix and Glycyrrhizae Radix complex (CAG) in men with moderate lower urinary tract symptoms (LUTS). Materials and methods: From November 2020 to January 2022, participants with International Prostate Symptom Score (IPSS) of 12-19 in two centers were recruited and randomize into three groups: a CAG 500 mg/day group (CAG 500), a CAG 1000 mg/day group (CAG 1000), and a placebo group (PG). They were treated for 12 weeks. The primary endpoint was change of IPSS at the end of study from baseline. Secondary end points included change of prostate specific antigen (PSA), testosterone, dihydrotestosterone (DHT), maximum urinary flow rate (Q max), post-void residual volume (PVR), International Index of Erectile Function (IIEF), and drug safety. Results: A total of 103 patients were able to finish the study according to the study protocol. Total IPSS and sub-scores (residual urine sensation, frequency, weak stream, hesistancy, nocturia, and quality of life) in CAG 500 and CAG 1000 were significantly improved at the 12th week compared to those of the PG. Changes of serum PSA, DHT, and testosterone levels at the 12th week from baseline did not show significant differences among the three groups. Q max and PVR changes did not show significant differences among the three groups either. Total IIEF and sub-scores (erectile function, orgasmic function, sexual desire, intercourse satisfaction) in CAG 1000 were significantly improved at 12th week compared to those in PG. No significant adverse events were found. Conclusions: CAG is well tolerated in patients with moderate LUTS. Treatment with CAG for 12 weeks has a therapeutic effect on moderate LUTS.

Implication of cystic fluid cytology of renal cell carcinoma on surgical practice.

OBJECTIVES: To evaluate the incidence of positive cystic fluid cytology and its risk factors in cystic renal cell carcinoma (RCC) addressing its implication on the current surgical practice. METHODS: All clinically diagnosed Bosniak III, IV cystic renal masses from March 2019 to August 2022 were studied prospectively. Database of patients' demographics and cystic tumor characteristics were recorded. Partial or radical nephrectomies were performed by either laparoscopic or robotic approach. Cystic fluid was collected right after specimen retrieval in the surgical field and examined by pathologist. Cytology results were compared to the demographic, perioperative variables using univariate and multivariate analysis. RESULTS: A total of 70 patients of histologically confirmed cystic RCC were included. Sixty seven patients underwent radical nephrectomy with laparoscopic or robotic approaches, while 3 patients underwent radical nephrectomy. There was no intraoperative cystic rupture or fluid spillage. Positive cystic fluid cytology findings were identified in 34 (48.6%) patients, while negative cystic fluid cytology were identified in 36 (51.4%) cases. Definite malignant cells were observed in 28 patients while the other six patients showed highly suspicious atypical cells. Histologically, 24 (70.8%) patients were proven clear cell RCC and 25 (73%) showed Fuhrman grade 1 or 2 in final histologic review in positive group. Univariate and multivariate regression analysis between positive and negative cytology groups showed that the presence of the malignant cells in cystic fluid was significantly associated with patients' age (> 55 years) and Bosniak grade of cystic tumor (p < 0.05). CONCLUSIONS: Definite malignant cells in cystic fluid cytology were observed through our study. Additionally, patients' age (> 55 years) and Bosniak grade were the significant risk factors of positive cytology in cystic RCC. Therefore, necessity of meticulous manipulation of cystic renal tumors, despite their clinical features, should not be underemphasized to avoid the least possible tumor cell seeding in case of cystic rupture when operating such high risk of positive cytology.

Fall risk related to subtype-specific alpha-antagonists for benign prostatic hyperplasia: a nationwide Korean population-based cohort study.

BACKGROUND: Subtype-specific alpha-antagonists are medications commonly prescribed for lower urinary-tract symptoms, benign prostatic hyperplasia in older populations. Our study aims to investigate the association between subtype-specific alpha-antagonists and fall risk. METHODS: A total of 4,202,739 men aged 60-75 years eligible for Korean Health Insurance Review and Assessment Service (HIRA) during 2017-2018 were enrolled retrospectively. After propensity score matching, 53,303 people in the exposed and unexposed groups were considered in the final study analysis. RESULTS: The subtype-specific alpha-antagonists significantly increased the risk of fall in the exposed cohort compared to the unexposed cohort (odds ratio [OR] 1.80; 95% confidence interval [CI] 1.62-2.00). Low income increased the fall risk only in the unexposed cohort (OR 1.34; 95% CI 1.04-1.73). A seasonal difference appeared only in the exposed cohort, with a significantly higher risk of fall in summer (OR 1.23; 95% CI 1.03-1.47). A total of 968 events occurred in the exposed group, and 455 of these falls occurred on the first day of medication (47%). CONCLUSIONS: Subtype-specific alpha-antagonists significantly increased the risk of falls, especially on the first day of drug initiation and during the summer season. Education on orthostatic hypotension and fall prevention should be implemented when prescribing subtype-specific alpha-antagonists.

Duration of diabetes mellitus and risk of kidney and bladder cancer: a longitudinal nationwide cohort study.

Previous studies have suggested that diabetes mellitus (DM) may increase the risk of kidney and bladder cancer; however, little is known about the duration of DM. We aimed to analyze the risk of kidney and bladder cancer according to the duration of DM in a longitudinal nationwide cohort. This study was conducted in a cohort of 9,773,462 participants ≥ 20 years old who underwent a National Health Examination in 2009 and were followed up until December 2017. Cox-proportional hazard models were used to evaluate the risk of kidney and bladder cancer in relation to the duration of DM. During follow-up (mean 7.3 years), kidney and bladder cancer occurred in 11,219 and 13,769 participants, respectively. DM was associated with an increased risk of kidney and bladder cancer (hazard ratio (HR), 95% confidence interval (95% CI); 1.14, 1.09-1.20 and 1.23, 1.17-1.28, respectively). Compared to fasting glucose < 100 mg/dL, impaired fasting glucose (IFG) and longer DM duration were associated with increased risks (HR, 95% CI): IFG (1.05, 1.01-1.10), new-onset DM (1.13, 1.03-1.24), DM < 5 years (1.11, 1.02-1.20), and DM ≥ 5 years (1.25, 1.15-1.36) in kidney cancer; IFG (1.05, 1.01-1.09), new-onset DM (1.10, 1.01-1.19), DM < 5 years (1.26, 1.18-1.35), and DM ≥ 5 years (1.34, 1.26-1.43) in bladder cancer, respectively. Our findings suggest that the subjects with IFG and longer duration of DM had a higher risk for kidney and bladder cancer than those without DM.

Effect of Li-ESWT on Testicular Tissue and Function in Androgen-Deficient Rat Model.

Low-intensity extracorporeal shockwave therapy (Li-ESWT), as a microenergy therapy, has the effects of inhibiting oxidative stress, antiapoptosis, and tissue repair, which is increasingly applied to a variety of diseases. Our research aims to explore the protective effects of Li-ESWT in the aging rat model and its possible molecular mechanism through in vivo and in vitro experiments. In vitro, TM3 Leydig cells incubated with H2O2 were treated with Li-ESWT at 4 energy levels (0.01, 0.05, 0.1, and 0.2 mJ/mm2). In vivo, we employed an androgen-deficient rat model to simulate male aging and treated it with Li-ESWT at three different energy levels (0.01, 0.05, and 0.2 mJ/mm2). Li-ESWT increased the expression of vascular endothelial growth factor (VEGF) in TM3 cells, improved antioxidant capacity, and reduced apoptosis, with the effect being most significant at 0.05 mJ/mm2 energy level. In androgen-deficient rat model, LI-ESWT can improve sperm count, motility, and serum testosterone level, enhancing tissue antioxidant capacity and antiapoptotic ability, and the effect is most significant at 0.05 mJ/mm2 energy level. Therefore, Li-ESWT at an appropriate energy level can improve sperm count, motility, and serum testosterone levels in androgen-deficient rat models, reduce oxidative stress in the testis, and increase antioxidant capacity and antiapoptotic abilities. The mechanism of this condition might be related to the increased VEGF expression in Leydig cells by Li-ESWT.

Retroperitoneoscopic lumbar sympathectomy for the treatment of primary plantar hyperhidrosis.

BACKGROUND: Primary plantar hyperhidrosis (PPH) is an idiopathic disease, characterized by excessive sweating of the feet. It leads to significant disturbance in private and professional daily lifestyle, due to excessive sweating. The aim of this study is to present the safety, efficacy and procedures of retroperitoneoscopic lumbar sympathectomy (RLS) for treatment of PPH. METHODS: RLS was performed 60 times in 30 patients (18 men, 12 women) with PPH in our institution from May 2019 to October 2020. All procedures were carried out by laparoscopy with retroperitoneal approach. Clinical data including patient demographics and perioperative, postoperative outcomes were evaluated. Recurrence of symptoms, and any adverse effects of surgery were evaluated after 7 to 30 days in outpatient clinic, and thereafter every 6 months. RESULTS: Mean age of patients was 33.6 (± standard deviation 10.8) years. Fourteen and fifteen patients were previously treated with medical therapy or endoscopic thoracic sympathectomy (ETS) respectively. Mean preoperative quality of life (QoL) score of patients was 91.8 (VERY BAD), but postoperative 12 months (QoL) score decreased to 29.1 (MUCH BETTER). There was no serious postoperative complication. During the mean 22 months of follow-up period, no compensatory sweating was observed. CONCLUSIONS: RLS can be a safe and effective surgical treatment for severe PPH, especially for the patients with persistent plantar sweating even after conservative management and ETS. RLS also could be offered to surgeons who are familiar with retroperitoneal space anatomy as feasible surgical treatment for PPH.

Cumulative obesity exposure increases the risk of kidney cancer: a longitudinal nationwide cohort study.

Obesity is one of the most important prognostic factors of kidney cancer. However, little is known regarding the cumulative impacts of obesity on kidney cancer risk. We aimed to analyze the dose- and time-dependent impact of obesity on kidney cancer risk using the Korean National Health Insurance System database. This longitudinal nationwide cohort study used data from the Korean National Health Insurance System database between 2012 and 2013. In total, 3,102,240 participants who received annual health examination more than four times consecutively were included in the final analysis. The primary endpoint was newly diagnosed kidney cancer according to the dose- and time-dependent impact of obesity. Dose-dependent impact was measured using body mass index (BMI) and waist circumference (WC), and time-dependent impact was measured using general and abdominal cumulative obesity exposure (gCOE and aCOE). COE was defined as the number of years since obesity diagnosis during the exposure period. We identified 1,831 participants with newly diagnosed kidney cancer (median follow-up: 4.3 years). The hazard ratios (HRs) for kidney cancer increased significantly alongside BMI and WC. The HRs for kidney cancer increased significantly in the higher gCOE groups (P for trend <0.001) as follows: 1 (1.33, 95% confidence intervals: 1.10-1.60), 2 (1.33, 1.08-1.63), 3 (1.55, 1.30-1.85), and 4 (1.82, 1.64-2.03) years. Similar trends were observed for aCOE (P for trend <0.001) as follows: 1 (1.42, 1.23-1.64), 2 (1.71, 1.46-2.02), 3 (1.76, 1.48-2.08), and 4 (2.11, 1.84-2.42) years. Risks of kidney cancer related to COE were much more pronounced in participants with the following characteristics: younger than 65 years old, male gender, diabetes, hypertension, and dyslipidemia. Longer COE was associated with an increased risk of kidney cancer in the Korean population. Participants with prolonged obesity and metabolic syndrome need active surveillance for kidney cancer.