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.

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.

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.

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.

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.

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.

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.

Does increased body mass index lead to elevated prostate cancer risk? It depends on waist circumference.

BACKGROUND: We examined the association between obesity and prostate cancer based on both body mass index (BMI) and waist circumference (WC) using the National Health Insurance System (NHIS) database for the entire male population of Korea. METHODS: A total of 1,917,430 men who underwent at least one health examination in 2009 without a previous diagnosis of any other cancer were tracked through December 2015. The hazard ratio (HR) and 95% confidence interval (CI) value for the association between prostate cancer and obesity were analyzed using multiple Cox regression model. Since there was a statistically significant interaction between WC and BMI, a multiple HR for prostate cancer was estimated with stratifying both WC and BMI to control the interaction between WC and BMI. RESULTS: Without considering WC as an adjustment factor, very weak association between BMI and prostate cancer development risk was observed. When WC was considered as an adjustment factor, no significant change in the HRs for prostate cancer development beyond the reference BMI was observed in the group with WC < 85 cm in the multivariable-adjusted models. However, in the group with WC ≥ 85 cm, the HRs for prostate cancer increased as the BMI increased beyond the reference BMI. In addition, there was a discrepancy in the trend of prostate cancer development according to BMI among the groups with different categories for WC. CONCLUSION: In groups with abdominal obesity, a significant linear relationship was observed between increasing BMI and prostate cancer risk. Higher the WC category, the stronger was the association with BMI, signifying that the association of BMI with risk of prostate cancer development depends on abdominal obesity.

Distinct mutation profiles between primary bladder cancer and circulating tumor cells warrant the use of circulating tumors cells as cellular resource for mutation follow-up.

BACKGROUND: While circulating tumor cells may serve as minimally invasive cancer markers for bladder cancers, the relationship between primary bladder cancers and circulating tumor cells in terms of somatic mutations is largely unknown. Genome sequencing of bladder tumor and circulating tumor cells is highlighted to identify the somatic mutations of primary bladder cancer. METHODS: Bladder cancer tissue was collected by transurethral resection of the bladder and preserved by snap-freezing. Circulating tumor cells were Isolated from the blood obtained before treatment. We performed whole exome sequencing of 20 matched pairs of primary bladder cancers and circulating tumor cells to identify and compare somatic mutations of these two different genomic resources. RESULTS: We observed that mutation abundances of primary bladder cancers and circulating tumor cells were highly variable. The mutation abundance was not significantly correlated between matched pairs. Of note, the mutation concordance between two resources was only 3-24% across 20 pairs examined, suggesting that the circulating tumor cell genomes of bladder cancer patients might be genetically distinct from primary bladder cancers. A relative enrichment of mutations belonging to APOBEC-related signature and a depletion of C-to-G transversions were observed for primary- and circulating tumor cells specific mutations, respectively, suggesting that distinct mutation forces might have been operative in respective lesions during carcinogenesis. CONCLUSIONS: The observed discrepancy of mutation abundance and low concordance level of mutations between genomes of primary bladder cancers and circulating tumor cells should be taken into account when evaluating clinical utility of circulating tumor cells for treatments and follow-up of bladder cancers. TRIAL REGISTRATION: Patients were selected and registered retrospectively, and medical records were evaluated.

Lycium chinense Mill improves hypogonadism via anti-oxidative stress and anti-apoptotic effect in old aged rat model.

Purpose: To evaluate the pharmacological effects of goji berry (Lycium chinense P. Mill) in an animal model of late-onset hypogonadism (LOH).Materials and methods: Thirty 18-month-old male Sprague-Dawley (SD) rats were used as the LOH aged rat model. Rats were divided into five groups: a control group (n = 6), low concentration goji berry extract group (150 mg/kg/day) (n = 6), high concentration goji berry extract group (300 mg/kg/day) (n = 6), low concentration goji berry complex extract group (150 mg/kg/day) (n = 6), and high goji berry complex concentration extract group (300 mg/kg/day) (n = 6). After six weeks of treatment, sperm counts and motility, serum testosterone level, androgen receptor (AR) expression, oxidative stress marker, and apoptotic factors were examined.Results: Goji berry extracts increased testosterone level to 2.07 ± 0.06 pmol/L in the goji berry 150 mg/kg group, 2.39 ± 0.08 pmol/L in the goji berry 300 mg/kg group, 2.97 ± 0.03 pmol/L in the goji berry complex 150 mg/kg group, and 3.34 ± 0.04 pmol/L in the goji berry complex 300 mg/kg group compared to 1.86 ± 0.03 pmol/L in the control group, respectively (p < .05). AR expressions were increased in testis tissue significantly but were not significant in prostate tissue.Conclusions: Goji berry might improve LOH by reversing testicular dysfunction via an anti-oxidative stress mechanism without inducing prostate disease.

A randomized, controlled study of treatment with ojayeonjonghwan for patients with late onset hypogonadism.

Objectives: We investigate the effects of Ojayeonjonghwan (KH-204) in men with late-onset hypogonadism (LOH) symptoms.Material and methods: Initial PSA, testosterone, lipid profile and questionnaires about LOH-related symptoms were checked. After 8 weeks of the treatment (control or KH-204), questionnaires and serological tests were repeated to evaluate the efficacy of the agent. The changes of variables in each group and the difference between two groups were compared.Results: A total of 78 men were enrolled, and randomly assigned to the control group (n = 39) or KH-204 group (n = 39). Baseline characteristics of both group are comparable. AMS total score of control and KH-204 group were both improved at 8 weeks (p = .010, <.001), and there was a statistically significant difference between the two groups (favorable in KH-204 group, p = .006). At 8 weeks, total IIEF score of control and KH-204 group were both improved, and there was no statistically significant difference in the degree of improvement between the two groups (p = .303). There was no statistically significant difference of laboratory findings, in intra-group changes and inter-group comparisons.Conclusions: KH-204 was found to be effective in all LOH symptoms without changing of laboratory results. KH-204 may be safely used for treatment of male with LOH-related symptoms.

The effects of oral administration of the novel muscarinic receptor antagonist DA-8010 on overactive bladder in rat with bladder outlet obstruction.

BACKGROUND: DA-8010 is a novel compound developed for the treatment of overactive bladder (OAB) and urinary incontinence. The aims of this study were to investigate the effects of DA-8010 on OAB in a rat model. METHODS: Study animals were divided into the following five groups of seven animals each: a sham-operated control group, a control group with partial bladder outlet obstruction (BOO) (OAB group), and three DA-8010 (doses of 0.3 mg/kg/day, 1 mg/kg/day, and 3 mg/kg/day, respectively) with partial BOO groups. Oral administration of the drugs was continued for 14 days after 2 weeks of partial BOO. After 4 weeks of partial BOO, cystometrography was performed in all groups. Additionally, pro-inflammatory cytokines, Rho-kinases, and histology of the bladder were analyzed. RESULTS: There was a significant increase in the contraction interval and a decrease in contraction pressure in the 3 mg/kg/day DA-8010 group versus those in the OAB group. Rho kinase was also significantly decreased in the DA-8010 3 mg/kg/day dosage treatment group. The increased ratio of collagen to smooth muscle after partial BOO was significantly attenuated in the DA-8010 3 mg/kg/day dosage group. CONCLUSIONS: Oral administration of DA-8010 at 3 mg/kg/day improved findings in an OAB rat model induced by partial BOO. Our results suggest that the novel muscarinic receptor antagonist DA-8010 may be a promising drug for treating patients with OAB.

Early and Synergistic Recovery Effect of Herbal Combination on Surgically Corrected Varicocele.

CONTEXT: Not all men presenting varicocele-associated infertility exhibit improved sperm quality or achieve pregnancy following varicocelectomy. Some combinations of specific natural herbs have been shown empirically to reduce oxidative stress and improve sperm quality. OBJECTIVE: We conducted a study to determine the effects of an herbal combination on sperm quality in varicocele-induced rats following varicocelectomy, hoping to find a new treatment approach to restore sperm quality following varicocelectomy. DESIGN: The research team designed an animal study. SETTING: The study took place in the Department of Urology at Seoul St. Mary's Hospital (Seoul, Republic of Korea). ANIMALS: Fifty white, male, Sprague-Dawley rats weighing 250 to 300 g each were used in the study. INTERVENTION: The rats were randomly assigned to 5 groups: (1) a control group (n = 10), (2) varicocele group (n = 10), (3) rats with varicocele and receiving varicocelectomy only (varicocelectomy group, n = 10), (4) rats with varicocele received varicocelectomy and oral administration with 200 mg/kg of an herbal combination for 4 wk (varicocelectomy + 200 mg/kg group, n = 10), and (5) rats with varicocele received varicocelectomy and oral administration with 400 mg/kg of an herbal com for 4 wk (varicocelectomy + 400 mg/kg group, n = 10). OUTCOME MEASURES: The study measured (1) sperm concentration and motility, (2) levels of reactive oxygen species (ROS), (3) concentrations of interleukin 6, interleukin 1ß, and tumor necrosis factor alpha (TNF-α), (4) apoptotic change, and (5) levels of heat shock protein (HSP). RESULTS: The sperm concentrations and motilities recovered after treatment in the varicocelectomy, varicocelectomy + 200 mg/kg, and varicocelectomy + 400 mg/kg groups. Significantly increased SOD and decreased ROS and cytokine levels were also observed. The apoptosis in the testes also was significantly decreased compared with the varicocele group. HSP70 in groups received varicocelectomy and administered with herbal combination was significantly decreased compared with the varicocelectomy group. CONCLUSIONS: The herbal combination was found to improve the sperm qualities, oxidative stress, and inflammation after varicocelectomy. Therefore, the herbal combination may provide a new and additional treatment for varicocele-associated infertility. For clinical application, further studies are needed to identify active ingredients in each herb and the mechanism by which each ingredient works, to standardize the herbal combination.

Extracorporeal shock wave therapy decreases COX-2 by inhibiting TLR4-NFκB pathway in a prostatitis rat model.

BACKGROUND: This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism. METHODS: RWPE-2 cells were randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 ß-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA. RESULTS: ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate. CONCLUSIONS: ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.

Is Primary Androgen Deprivation Therapy a Suitable Option for Asian Patients With Prostate Cancer Compared With Radical Prostatectomy?

BACKGROUND: We conducted a comparative survival analysis between primary androgen deprivation therapy (PADT) and radical prostatectomy (RP) based on nationwide Korean population data that included all patients with prostate cancer. MATERIALS AND METHODS: This study enrolled 4,538 patients with prostate cancer from the National Health Insurance Service (NHIS) database linked with Korean Central Cancer Registry data who were treated with PADT or RP between January 1, 2007, and December 31, 2014. Kaplan-Meier and multivariate survival analyses stratified by stage (localized and locally advanced) and age (<75 and ≥75 years) were performed using a Cox proportional hazards model to evaluate treatment effects. RESULTS: Among 18,403 patients from the NHIS database diagnosed with prostate cancer during the study period, 4,538 satisfied inclusion criteria and were included in the analyses. Of these, 3,136 and 1,402 patients underwent RP or received PADT, respectively. Risk of death was significantly increased for patients who received PADT compared with those who underwent RP in the propensity score-matched cohort. In subgroup analyses stratified by stage and age, in every subgroup, patients who received PADT had a significantly increased risk of death compared with those who underwent RP. In particular, a much greater risk was observed for patients with locally advanced prostate cancer. CONCLUSIONS: Based on a nationwide survival analysis of nonmetastatic prostate cancer, this study provides valuable clinical implications that favor RP over PDAT for treatment of Asian populations. However, the possibility that survival differences have been overestimated due to not accounting for potential confounding characteristics must be considered.

Association of body mass index with bladder cancer risk in men depends on abdominal obesity.

PURPOSE: The previous epidemiological studies about the associations between obesity and bladder cancer risk have reported inconsistent results. Therefore, we analyzed whether the abdominal obesity effected on the risk of developing bladder cancer according to body mass index (BMI) using nationally representative data from the National Health Insurance System (NHIS). PATIENTS AND METHODS: Among people who underwent at least one health examination from 2009 to 2012 in Korea, 11,823,876 men without a previous diagnosis of bladder cancer were followed up until December 2015. Multiple Cox regression analysis was conducted to determine the hazard ratio (HR) and 95% confidence interval (CI) for the association between bladder cancer and BMI or waist circumference (WC). RESULTS: Significant upward trends in the risk of bladder cancer were observed with increasing BMI or WC according to the multivariate-adjusted model. However, the association between BMI and bladder cancer is influenced by the presence of abdominal obesity. In the group with WC < 90 cm, there was no significant change in the HRs for bladder cancer development beyond the reference BMI. In contrast, the HRs for bladder cancer showed statistically significant increase as the BMI increased beyond the reference BMI in the group with WC ≥ 90 cm. CONCLUSION: This population-based study showed that increasing BMI and increasing WC were risk factors for developing bladder cancer in men, independent of confounding variables. However, there was a discrepancy in the trend of bladder cancer development according to BMI between the groups with abdominal obesity and without abdominal obesity.

A randomized, prospective study of laparoendoscopic single-site plus one-port versus mini laparoscopic technique for live donor nephrectomy.

PURPOSE: To compare the clinical outcomes of laparoendoscopic single-site plus one-port donor nephrectomy (LESSOP-DN) and mini laparoscopic donor nephrectomy (MLDN). METHODS: A prospective randomized controlled trial was conducted from December 2014 to February 2016 in donors scheduled for left donor nephrectomy. Donor and recipient demographics and clinical outcomes including pain scores and questionnaires (BIQ: body image questionnaire, SF-36, patient-reported overall convalescence) were also compared. RESULTS: A total of 121 eligible donors were recruited, of which 99 donors who were scheduled to undergo an operation on their left side were randomized into LESSOP-DN (n = 50) and MLDN (n = 49) groups. There were no significant demographic differences between the two groups. The renal extraction time in the LESS-DN group was shorter than that in the MLDN group (75.89 ± 13.01 vs. 87.31 ± 11.38 min, p < 0.001). Other perioperative parameters and complication rates were comparable between the two groups. The LESSOP-DN group had a smaller incision length than the MLDN group (4.89 ± 0.68 vs. 6.21 ± 1.11 cm, p < 0.001), but cosmetic scores and body image scores were similar in the two groups (p = 0.905, 0.217). Donor quality of life (SF-36) and recovery and satisfaction data were comparable between the two groups. Delayed graft function (DGF) occurred in one recipient undergoing MLDN procedure (2.1%) and progressed to graft failure. CONCLUSIONS: There were no differences in cosmetic satisfaction between groups despite the smaller incision size of LESSOP-DN. Safety parameters and subjective measures of postoperative morbidity were similar between the two groups.

Engineered Mesenchymal Stem Cells Expressing Stromal Cell-derived Factor-1 Improve Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Sprague⁻Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ± 0.07 in the normal group, 0.27 ± 0.08 in the DM ED group, 0.42 ± 0.11 in the DM ED + BM-MSC group, and 0.58 ± 0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p < 0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p < 0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p < 0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.

Prediction of stone-free status and complication rates after tubeless percutaneous nephrolithotomy: a comparative and retrospective study using three stone-scoring systems and preoperative parameters.

PURPOSE: To investigate the factors predictive of surgical outcomes of tubeless percutaneous nephrolithotomy (TPCNL) and to compare the predictability and accuracy of the Guy's stone score, S.T.O.N.E. nephrolithometry, and CROES nomogram. PATIENTS AND METHODS: We reviewed retrospectively the surgical outcomes recorded consecutively and imaging data of preoperative computed tomography scans of 141 patients who had undergone TPCNL from June 2012 to October 2015. Guy's, S.T.O.N.E., and CROES stone-scoring systems (SSSs) and other prognostic factors were assessed using univariate and multivariate statistical analyses. RESULTS: The initial stone-free and complication rates after TPCNL were 78.7 (111/141) and 17.0 % (24/141). On univariate analysis, all three scoring systems were identified as significant factors in terms of stone-free rate (SFR). The multivariate logistic regression analysis showed that the Guy's stone score and stone burden ≥385 mm2 had significant correlations with stone-free status [odds ratios (OR) = 3.220, p = 0.001 and OR = 6.451, p = 0.002, respectively]. Guy's stone score (OR = 1.879, p = 0.013) was an independent risk factor for the development of complications. The area under the receiver operating characteristic (ROC) curves for the Guy's, S.T.O.N.E., and CROES SSSs and stone burden showed good results (0.821, 0.816, 0.820, and 0.800, respectively). Pairwise comparison of ROC curves showed that there was no significant difference between each final score and stone burden. CONCLUSIONS: Of the three scoring systems, Guy's stone score was the only significant predictive factor for SFR and complication rates after TPCNL in the multivariate logistic regression analysis. Stone burden was significantly associated with a postoperative stone-free status (SFS).

The influence of prior laparoscopic experience on learning laparoendoscopic single site surgery: a prospective comparative preliminary study using cystorraphy in a live porcine model.

BACKGROUND: The purpose of this study is to assess the impact of prior laparoscopic experience on the ability to learn laparoendoscopic single site surgery (LESS) skills. METHODS: A total of 33 urologists who completed a training program in LESS surgery were recruited for this study. After completing the educational course and training, the study participants demonstrated LESS suturing and knot-tying via a 2-cm cystotomy in a live porcine model for 15 min. An objective structured assessment of technical skills (OSATS) was used to evaluate videos of each participant's procedure. The participants were divided according to laparoscopic experience; advanced experienced group (AS), intermediate experienced group (IS), novice group (NS). RESULTS: Three participants in the NS group completed the porcine cystorrhaphy in 15 min (30.0%), 3 (25.0%) completed the task in the IS group, and 3 (27.2%) completed it in the AS group. There were no statistically significant differences in the mean total OSATS quality score (NS; 16.7, IS; 18.5, AS; 16.8) among the 3 groups. Concerning all each assessment, there were also no statistically significant difference. Additionaly, the mean total OSATS quantity score (NS; 4.1, IS; 3.5, AS; 4.3) did not differ significantly among groups. The NS group succeeded a mean of 1.4 knots, the IS group succeeded 0.9, and the AS group 1.3 (p = 0.727). CONCLUSIONS: There was no significant difference among the groups in LESS proficiency after training. Surgeons who were novices in conventional laparoscopic surgery reached comparable scores to those of experienced laparoscopic surgeons after training.