Evaluation of histological variants of upper tract urothelial carcinoma as prognostic factor after radical nephroureterectomy.

PURPOSE: To evaluate the impact of variant histology on patients with upper tract urothelial carcinoma (UTUC) survival outcomes. MATERIALS AND METHODS: A total of 519 patients underwent radical nephroureterectomy without neoadjuvant therapy for UTUC at a single institution between May 2003 and December 2019. Multivariate Cox regression analysis evaluated the impact of variant histology on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Among 84 patients (16.2%) with variant histology, the most frequent variant type was squamous cell differentiation (64.3%), followed by glandular differentiation (25.0%) and sarcomatoid variant (2.4%). They showed pathologically advanced T stage (for ≥ T3, 59.5% vs 33.3%, p < 0.001), higher tumor grade (96.4% vs 85.7%, p = 0.025), and higher rates of lymph node metastasis (17.9% vs 7.8%, p = 0.015), angiolymphatic invasion (41.7% vs 25.7%, p = 0.003), tumor necrosis (57.1% vs 29.0%, p < 0.001) and positive surgical margin (13.1% vs 5.7%, p = 0.015). On multivariate Cox regression analyses, variant histology was significantly associated with worse PFS (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.55-3.21; p < 0.001), CSS (HR 2.67; 95% CI 1.35-5.30; p = 0.005) and OS (HR 2.22; 95% CI 1.27-3.88; p = 0.005). In subgroup analysis, no significant survival gains of adjuvant chemotherapy occurred in patients with variant histology. CONCLUSIONS: Variant histology was associated with adverse pathologic features and poor survival outcomes. Our results suggest that patients with variant histology may require a close follow-up schedule and novel adjuvant therapy other than chemotherapy postoperatively.

Oropharyngeal, proximal colonic, and vaginal microbiomes of healthy Korean native black pig gilts.

BACKGROUND: Exploring the microbiome in multiple body sites of a livestock species informs approaches to promote its health and performance through efficient and sustainable modulation of these microbial ecosystems. Here, we employed 16S rRNA gene sequencing to describe the microbiome in the oropharyngeal cavity, proximal colon, and vaginal tract of Jeju Black pigs (JBP), which are native to the Korean peninsula. RESULTS: We sampled nine 7-month-old JBP gilts raised under controlled conditions. The most abundant phyla that we found within the oropharyngeal microbiota were Proteobacteria, Bacteroidetes, Fusobacteria and Firmicutes, collectively providing core features from twenty-five of their genera. We also found a proximal colonic microbial core composed of features from twenty of the genera of the two predominant phyla, Firmicutes, and Bacteroidetes. Remarkably, within the JBP vaginal microbiota, Bacteroidetes dominated at phylum level, contrary to previous reports regarding other pig breeds. Features of the JBP core vaginal microbiota, came from seventeen genera of the major phyla Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. Although these communities were distinct, we found some commonalities amongst them. Features from the genera Streptococcus, Prevotella, Bacillus and an unclassified genus of the family Ruminococcaceae were ubiquitous across the three body sites. Comparing oropharyngeal and proximal colonic communities, we found additional shared features from the genus Anaerorhabdus. Between oropharyngeal and vaginal ecosystems, we found other shared features from the genus Campylobacter, as well as unclassified genera from the families Fusobacteriaceae and Flavobacteriaceae. Proximal colonic and vaginal microbiota also shared features from the genera Clostridium, Lactobacillus, and an unclassified genus of Clostridiales. CONCLUSIONS: Our results delineate unique and ubiquitous features within and across the oropharyngeal, proximal colonic and vaginal microbial communities in this Korean native breed of pigs. These findings provide a reference for future microbiome-focused studies and suggest a potential for modulating these communities, utilizing ubiquitous features, to enhance health and performance of the JBP.

Validation of acoustic voided volume measure: a pilot prospective study.

PURPOSE: We evaluated the accuracy and reliability of a new smartphone-based acoustic voided volume (VV) measurement application compared to VV estimation based on the measurement of urine volume in a bladder by ultrasound bladder scan. PATIENTS AND METHODS: A total of 53 subjects from 01/2021 to 09/2021 were prospectively enrolled. Bladder scan-based VV estimation is based on the difference in the volume of urine in a bladder measured before urination and volume measured after urination. The acoustic VV measurement is based on smartphone-based acoustic VV measurement mobile application. VV estimates for the same void were compared between two techniques. Urinary measures were obtained from 49 male subjects resulting in a total of 245 measurements for analysis. VV measures were compared using Pearson's correlation coefficient (PCC), evaluation of observed versus predicted VV measures using linear regression fit indices, and Bland-Altman method. RESULTS: VV between the two techniques revealed strong correlation (PCC 0.811, p < 0.001). Means of the number of measurements per patient and inpatient days for measurements analyzed are 5 and 2.7, respectively. In 245 measurements, VV measured by bladder scan is 238.69 ± 122.32 mL, VV measured by mobile application is 254.69 ± 119.28 mL, and their difference of two measurements is 16 ± 74.29 mL. CONCLUSION: Through the comparison with VV estimated by ultrasound bladder scan, which is a technology to measure the urine volume in a bladder, it was confirmed that the smartphone-based acoustic VV measurement application proudP® is accurate.

Computer tomography-based shape of tumor contour and texture of tumor heterogeneity are independent prognostic indicators for clinical T1b-T2 renal cell carcinoma.

PURPOSE: To evaluate association between computer tomography (CT)-based features of renal cell carcinoma (RCC) and survival outcomes. METHODS: Data of 958 patients with clinical T1b-T2 RCC who underwent partial/radical nephrectomy from June 2003 to March 2022 were retrospectively evaluated. CT images of patients were reviewed by two radiologists for texture analysis of tumor heterogeneity and shape analysis of tumor contour. Patients were divided into three groups according to patterns of CT-based features: (1) favorable feature group (n = 117); (2) intermediate feature group (n = 606); and (3) unfavorable feature group (n = 235). Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed to evaluate overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS). RESULTS: RCCs with unfavorable CT-based feature showed larger size on CT, higher nuclear grade, higher rate of histologic necrosis, and higher rate of capsular invasion than those in the other two groups (all p < 0.001). Unfavorable feature was associated with poorer OS (p = 0.001), CSS (p < 0.001), and RFS (p < 0.001) on Kaplan-Meier analysis. In multivariate analysis, intermediate and unfavorable features were independent predictors for recurrence (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.09-5.79, p = 0.031 and HR 3.71, 95% CI 1.58-8.73, p = 0.003, respectively), but not for overall death or RCC-specific death. CONCLUSIONS: A combination of irregular tumor contour feature with heterogeneous tumor texture feature on CT is associated with poor RFS in clinical T1b-T2 RCC preoperatively.

Clinical value of prostate health index as an indicator for recommending magnetic resonance imaging in patients with gray-zone prostate-specific antigen level.

PURPOSE: To evaluate the usefulness of prostate health index (PHI) as an indicator for recommending magnetic resonance imaging (MRI) in patients with prostate-specific antigen (PSA) gray zone level < 10 ng/mL. METHODS: 443 patients who underwent prostate biopsy (PB) after serum PHI test and MRI between April 2019 and December 2022 were enrolled. For patients with visible lesion on MRI with Prostate Imaging Reporting and Data System Score (PI-RADS) ≥ 3, MRI-targeted PB was performed in addition to systematic 12-core PB. RESULTS: The optimal cutoff value of PHI for predicting PI-RADS ≥ 3 lesions was 39.6, which was significantly associated with overall prostate cancer (OR 3.07, p = 0.018) and clinically significant prostate cancer (csPCa) (OR 4.15, p = 0.006) at MRI-targeted PB cores. When MRI was restricted to patients with PHI ≥ 39.6 alone, 28.7% of unnecessary MRI could be saved at the cost of missing 13.6% of csPCa. When omitting MRI for patients with PHI < 39.6 and PSAD < 0.12 ng/mL2, unnecessary MRI could be reduced by 20.1% with the risk of missing 6.2% of csPCa. With addition of systematic PB, 21.0% of patients with negative MRI-targeted PB were diagnosed as csPCa. CONCLUSIONS: For patients in PSA gray zone, PHI of 39.6 might be an indicator for MRI and further MRI-targeted PB in additional to PSAD of 0.12 ng/mL2, reducing 20.1% of unnecessary MRI with the minimal risk of missing 6.2% of csPCa. To maximize csPCa detection, combining both MRI-targeted and systematic PB should be also considered.

Bacillus-supplemented diet improves growth performance in Jeju native pigs by modulating myogenesis and adipogenesis.

Probiotics are used in pigs as nutritional supplements to improve health and induce the development of muscle and adipose tissue for enhancing growth performance and harvesting quality meat. In this study, we investigated the effects of Bacillus-based probiotic supplementation on the physiological and biochemical changes in Jeju native pigs (JNPs), including growth performance, backfat layers, blood parameters, serum IgG levels, myogenic and adipogenic markers, and expression of inflammatory markers. Average daily gain and feed efficiency were higher in the Bacillus diet group than in the basal diet group, while backfat thickness was lower in the Bacillus diet group than in the basal diet group. Blood biochemical parameters and hematological profiles were not altered significantly by Bacillus-based probiotic supplementation. Serum IgG concentration increased in the Bacillus diet group compared to the basal diet group. The Bacillus diet group showed increased adipogenic and myogenic markers expression in the longissimus dorsi muscle and adipose tissues. Overall, the data suggest that the Bacillus-based probiotics-supplemented diet regulates myogenesis and adipogenesis in JNPs and improves growth performance. We postulate that this may be due to the changes in the gut microbiota of pigs due to probiotic supplementation.

Hybrid model for daily streamflow and phosphorus load prediction.

Environmental factors, such as climate change and land use changes, affect water quality drastically. To consider these, various predictive models, both process-based and data-driven, have been used. However, each model has distinct limitations. In this study, a hybrid model combining the soil and water assessment tool and the reverse time attention mechanism (SWAT-RETAIN) was proposed for predicting daily streamflow and total phosphorus (TP) load of a watershed. SWAT-RETAIN was applied to Hwangryong River, South Korea. The hybrid model uses the SWAT output as input data for the RETAIN. Spatial, meteorological, and hydrological data were collected to develop the SWAT to generate high temporal resolution data. RETAIN facilitated effective simultaneous prediction. The SWAT-RETAIN exhibited high accuracy in predicting streamflow (Nash-Sutcliffe efficiency (NSE): 0.45, root mean square error (RMSE): 27.74, percent bias (PBIAS): 22.63 for test sets), and TP load (NSE: 0.50, RMSE: 423.93, PBIAS: 22.09 for test sets). This result was evident in the performance evaluation using flow duration and load duration curves. The SWAT-RETAIN provides enhanced temporal resolution and performance, enabling the simultaneous prediction of multiple variables. It can be applied to predict various water quality variables in larger watersheds.

Comparison of Differential Functional Outcomes After Partial Nephrectomy Between Moderate and High Complex Renal Tumor Evaluated with Diethylenetriamine Pentaacetic Acid Scan: A Propensity Score Matched Analysis.

OBJECTIVE: The aim of this study was to compare functional outcomes after partial nephrectomy (PN) between moderate and high complex renal tumors evaluated with a diethylenetriamine pentaacetic acid (DTPA) scan [moderate vs. high: RENAL nephrometry score (RNS) 7-9 vs. 10-12]. METHODS: From January 2004 to December 2019, 471 patients with an RNS of 7-9 (moderate) and 164 patients with an RNS of 10-12 (high) who underwent PN were analyzed for renal function outcomes. The glomerular filtration rate (GFR) was measured using a DTPA scan and calculated the GFR using the Modification of Diet in Renal Disease (MDRD) formula, respectively. Trifecta/pentafecta outcome, recurrence-free survival, and overall survival were compared after propensity score matched analysis (PSMA). RESULTS: After PSMA, 156 cases in each group were matched without significant difference in the preoperative factor. At the postoperative first year, there was no significant difference in the trifecta (p = 0.320), MDRD-based (p = 0.729), or DTPA-based pentafecta achievement rate (p = 0.964) between groups. At postoperative 5 years, DTPA-based total GFR (93.6% vs. 93.8%) and the operated kidney GFR preservation rate (89.9% vs. 81.7%) did not differ significantly (p > 0.05). Kaplan-Meier survival analysis showed no significant differences in survival outcomes (p > 0.05). Significant predictors of de novo chronic kidney disease (CKD) stage 3 or higher at the postoperative first year were age [hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.03-1.17, p = 0.005] and preoperative DTPA-based total GFR (HR 0.94, 95% CI 0.91-0.98, p = 0.001). CONCLUSION: High complex tumors can be treated with PN without significant deterioration in renal function. The postoperative function of the operated kidney was preserved by up to 80% in the long term compared with the preoperative period. However, PN should be selectively performed with caution to avoid the occurrence of postoperative CKD.

Cosmesis and feasibility of transvaginal natural orifice Specimen extraction (NOSE) for large organ specimen: a prospective pilot study.

BACKGROUND: This study aimed to evaluate cosmetic outcomes and feasibility of transvaginal natural orifice specimen extraction (NOSE) in patients who underwent laparoscopic or robotic surgery for the treatment of benign or malignant diseases of the kidney, liver, stomach, adrenal gland, and bladder. METHODS: This prospective study was conducted at a tertiary hospital between March 2015 and May 2020. The main outcome was cosmetic outcomes of scars assessed using the Patient and Observer Scar Assessment Scale (POSAS) 1 and 8 weeks after surgery. The secondary outcomes were postoperative pain, operating time, and complications. Sexual function was assessed using the Female Sexual Function Index (FSFI) questionnaire 6 months after surgery in 17 patients who were sexually active at the time of surgery. RESULTS: A total of 38 transvaginal NOSE procedures were performed for the extraction of 33 kidneys, 2 livers, 1 stomach, 1 adrenal gland, and 1 bladder. Observers rated pigmentation and relief scores as most deviant from normal skin (2.9 ± 1.7, 3.0 ± 2.1 at postoperative 1 week; 3.6 ± 1.9, 3.5 ± 2.2 at postoperative 8 weeks, respectively), but the overall scores of each item were low. The patients' overall satisfaction with postoperative scars was high, and the mean scores for pain and itching were low, with significant improvement from the first week to the eighth week (P = 0.014 and P = 0.006, respectively). Patients also reported low scores on vaginal assessment items, indicating better symptoms, and bleeding improved significantly between the two time points (P = 0.001). Postoperative pain was reduced from moderate during the first 24 h after surgery to mild after 24 h. The mean operative time of the transvaginal NOSE procedure was 28.3 ± 13.3 min. No postoperative complications were associated with the procedure. The mean FSFI total score was 21.2 ± 8.7 (cutoff score for dysfunction is 21), with higher scores indicating better sexual functioning. CONCLUSION: Transvaginal NOSE seems to be a feasible procedure with promising cosmetic benefits, for patients who undergo minimally invasive surgery for large organs including the kidney, liver, stomach, adrenal gland, and bladder. A prospective randomized clinical trial is needed to provide solid evidence to support transvaginal NOSE. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05113134).

Predicting factor analysis of postoperative complications after robot-assisted radical cystectomy: Multicenter KORARC database study.

OBJECTIVES: To evaluate postoperative complications following robot-assisted radical cystectomy in patients diagnosed with bladder cancer and reveal if there are predictors for postoperative complications. METHODS: Prospectively collected medical records of 730 robot-assisted radical cystectomy patients between 2007/04 and 2019/05 in 13 tertiary referral centers were reviewed. Perioperative outcomes were compared between two groups by postoperative complications (complication vs non-complication). We assessed recurrence-free survival, cancer-specific survival, and overall survival between groups. Regression analyses were implemented to identify factors associated with postoperative complications. RESULTS: Any total and high-grade complication (Clavien-Dindo grade ≥3) rates were 57.8% and 21.1%, respectively. Patients in complication group had significantly higher proportion of diabetes mellitus (P = 0.048), chronic kidney disease (P = 0.011), dyslipidemia (P < 0.001), longer operation time (P = 0.001), more estimated blood loss (P = 0.001), and larger intraoperative fluid volume (P < 0.001). There was a significant difference in cancer-specific survival (log-rank P = 0.038, median cancer-specific survival: both groups not reached). Dyslipidemia (odds ratio 2.59, P = 0.002) and intraoperative fluid volume (odds ratio 1.0002, P = 0.040) were significantly associated with high-grade postoperative complications. Diabetes mellitus (odds ratio 1.97, P = 0.028), chronic kidney disease (odds ratio 1.89, P = 0.046), dyslipidemia (odds ratio 5.94, P = 0.007), and intraoperative fluid volume (odds ratio 1.0002, P = 0.009) were significantly associated with any postoperative complications. CONCLUSIONS: Patients with diabetes mellitus, chronic kidney disease, dyslipidemia, or a relatively large intraoperatively infused fluid volume are more likely to develop postoperative complications. Patients with postoperative complications might have a possibility of lower cancer-specific survival rate.

The ThiL enzyme is a valid antibacterial target essential for both thiamine biosynthesis and salvage pathways in Pseudomonas aeruginosa.

Thiamine pyrophosphate (TPP) is an essential cofactor for various pivotal cellular processes in all living organisms, including bacteria. Thiamine biosynthesis occurs in bacteria but not in humans; therefore, the enzymes in this pathway are attractive targets for antibiotic development. Among these enzymes, thiamine monophosphate kinase (ThiL) catalyzes the final step of this pathway, phosphorylating thiamine monophosphate to produce TPP. Here, we extensively investigated ThiL in Pseudomonas aeruginosa, a major pathogen responsible for hospital-acquired infections. We demonstrate that thiL deletion abolishes not only thiamine biosynthesis but also thiamine salvage capability and results in growth defects of the ΔthiL strain even in the presence of thiamine derivatives, except for TPP. Most importantly, the pathogenesis of the ΔthiL strain was markedly attenuated, compared with that of WT cells, with lower inflammatory cytokine induction and 103-104-fold decreased bacterial loads in an in vivo infection model in which the intracellular TPP level was in the submicromolar range. To validate P. aeruginosa ThiL (PaThiL) as a drug target, we further characterized its biochemical properties, determining a Vmax of 4.0 ± 0.2 nmol·min-1 and Km values of 111 ± 8 and 8.0 ± 3.5 µm for ATP and thiamine monophosphate, respectively. An in vitro small-molecule screening assay identified PaThiL inhibitors including WAY213613, a noncompetitive inhibitor with a Ki value of 13.4 ± 2.3 µm and potential antibacterial activity against P. aeruginosa These comprehensive biological and biochemical results indicate that PaThiL represents a potential drug target for the development of an augmented repertoire of antibiotics against P. aeruginosa.

Discovery of Leishmania donovani topoisomerase IB selective inhibitors by targeting protein-protein interactions between the large and small subunits.

Visceral leishmaniasis (VL) is a fatal infectious disease caused by viscerotropic parasitic species of Leishmania. Current treatment options are often ineffective and toxic, and more importantly, there are no clinically validated drug targets available to develop next generation therapeutics against VL. Topoisomerase IB (TopIB) is an essential enzyme for Leishmania survival. The enzyme is organized as a bi-subunit that is distinct from the monomeric topoisomerase I of human. Based on this unique feature, we synthesized peptides composed of partial amino acid sequences of small subunit of Leishmania donovani (Ld) TopIB to confirm a decrease in catalytic activity by interfering the interaction between the two subunits. One of the synthetic peptides, covering essential amino acids for catalytic activity of LdTopIB, interrupted the enzymatic activity. Next, we examined 151 compounds selected from virtual screening in a functional assay and identified three LRL-TP compounds with a significant decrease in LdTopIB activity (IC50 of LRL-TP-85: 1.3 µM; LRL-TP-94: 2.9 µM; and LRL-TP-101: 35.3 µM) and no effects on Homo sapiens (Hs) TopIB activity. Based on molecular docking, the protonated tertiary amine of inhibitors formed key interactions with S415 of the large subunit. The EC50 values of LRL-TP-85, LRL-TP-94, and LRL-TP-101 were respectively 4.9, 1.4, and 27.8 µM in extracellular promastigote assay and 34.0, 53.7, and 11.4 µM in intracellular amastigote assay. Overall, we validated the protein-protein interaction site of LdTopIB as a potential drug target and identified small molecule inhibitors with anti-leishmanial activity.

Evaluation of functional outcome of bilateral kidney tumors after sequential surgery.

BACKGROUND: There are limited data concerning patients treated with sequential bilateral kidney surgery. Current guidelines still lack an optimal surgical sequencing approach. We evaluated renal functional outcomes after sequential partial nephrectomy (PN) and radical nephrectomy (RN) in patients with bilateral renal cell carcinoma (RCC). METHODS: A propensity score matched cohort of 267 patients (synchronous bilateral RCCs, N = 44 [88 lesions]; metachronous bilateral, N = 45 [90 lesions]; unilateral, N = 178) from two tertiary institutions were retrospectively analyzed. Synchronous bilateral RCCs were defined as diagnosis concomitantly or within 3 months of former tumor. Renal functional outcomes were defined as estimated glomerular filtration rate (eGFR) changes and de novo chronic kidney disease (CKD, stage ≥3) after surgery. Renal functional outcomes and clinical factors predicting de novo CKD were assessed using descriptive statistics and Cox regression analysis. RESULTS: In subgroup of bilateral RCCs, patients underwent sequential PN (N = 48), PN followed by RN (N = 8), or RN followed by PN (N = 25). Final postoperative estimated glomerular filtration rates (eGFRs) were 79.4, 41.4, and 61.2 ml/minute/1.73 m2, respectively (p = 0.003). There were significant differences in eGFR decline from baseline and de novo chronic kidney disease (CKD stage ≥ III) among groups, with PN followed by RN group showing the worst functional outcomes (all p <  0.05). Moreover, sequential PN subgroup in bilateral RCC showed significantly higher rate of de novo CKD than unilateral RCC group (13.8% vs. 6.9%, p = 0.016). On multivariate analysis, hypertension (p = 0.010) and surgery sequence (PN followed by RN, p <  0.001) were significant predictors of de novo CKD. CONCLUSIONS: The surgery sequence should be prudently determined in bilateral renal tumors. PN followed by RN showed a negative impact on renal functional preservation. Nephron-sparing surgery should be considered for all amenable bilateral RCCs.

Oncological outcome according to attainment of pentafecta after robot-assisted radical cystectomy in patients with bladder cancer included in the multicentre KORARC database.

OBJECTIVES: To investigate the oncological significance of a robot-assisted radical cystectomy (RARC)-related pentafecta in patients with bladder cancer. PATIENTS AND METHODS: Using the KORARC database, which includes data from 12 centres, data from 730 patients who underwent RARC between April 2007 and May 2019 were prospectively collected and retrospectively analysed. Pentafecta was achieved if patients met all of the following criteria: (i) negative soft tissue surgical margin; (ii) ≥16 lymph nodes removed; (iii) no major complications (Clavien-Dindo grade 3-5) within 90 days; (iv) no clinical recurrence within the first 12 months; and (v) no ureteroenteric stricture. Patients were divided into two groups according to pentafecta attainment, and a comparison of overall survival (OS) and cancer-specific survival (CSS) using multivariate Cox proportional analysis was then carried out. RESULTS: Of the 730 patients included in this analysis, 208 (28.5%) attained the RARC pentafecta; the remaining 522 (71.5%) did not. The mean age of the patients was 64.67 years, 85.1% were men, 53.6% received a conduit, 37.7% received orthotopic neobladders and the total complication rate was 57.8%. Those who attained the pentafecta received more neobladders (P = 0.039), were more likely to be treated with the intracorporeal technique (P < 0.001), had longer operating times (P = 0.020) and had longer console time (P = 0.021) compared with those who did not attain the pentafecta. Over a mean of 31.1 months of follow-up, the pentafecta attainment group had significantly higher OS and CSS rates compared with the non-attainment group (10-year OS 70.4% vs 58.1%, respectively [P = 0.016]; 10-year CSS 87.8% vs 70.0%, respectively [P = 0.036]). Multivariate analysis showed that the RARC pentafecta was a significant predictor of overall mortality (hazard ratio 0.561; P = 0.038). CONCLUSIONS: Patients who attained the RARC pentafecta had significantly better survival outcomes compared with those who did not. These criteria could be used to standardize assessment of the surgical quality of RARC. In the future, a similar study using an independent cohort is warranted to confirm our results.

Clinical outcomes and prognosis of metastatic prostate cancer patients ≤ 60-year-old.

PURPOSE: Metastatic prostate cancer (mPCa) rarely occurs under the age of 60, and we aim to evaluate the clinical outcomes and prognosis of mPCa patients ≤ 60-year-old. METHODS: Two thousand and eighty-three patients were treated with mPCa between April 2003 and May 2020. Clinicopathological characteristics between groups, biochemical recurrence (BCR)-free survival, and overall survival (OS) were assessed. Subgroup analysis was performed on patients ≤ 60 years. Multivariable cox regression was used for survival analysis. RESULTS: Three hundred and seventy-five patients (> 60 years: older) and 115 patients (≤ 60 years: young) were identified. 5-year BCR-free survival rates were 38.8% in young and 74.1% in older group (p < 0.001). 5-year OS were 88.1% in young and 96.5% in older group (p = 0.006). The significant factor associated with BCR was age > 60 (hazard ratio [HR] = 0.67, 95% confidence [CI]: 0.36-0.94, p = 0.017). The significant predictors of OS were age > 60 (HR 0.40, CI 0.18-0.91, p = 0.028) and local definitive treatment (HR 0.29, CI 0.13-0.64, p = 0.002). For the subgroup analysis, median BCR-free survival was significantly shorter in younger (≤ 56) group (14 mo vs. 27 mo, p = 0.026), and the median OS was significantly different (p = 0.048). CONCLUSIONS: In mPCa patients ≤ 60-year-old, BCR occurs earlier and OS is significantly reduced than older patients. Therefore, special caution is mandatory when treating these mPCa patients.

Mirabegron for treatment of overactive bladder symptoms in patients with Parkinson's disease: A double-blind, randomized placebo-controlled trial (Parkinson's Disease Overactive bladder Mirabegron, PaDoMi Study).

AIMS: This study aimed to investigate the efficacy and safety of mirabegron for Parkinsonism patients with overactive bladder (OAB) symptoms in a randomized, placebo-controlled, multicenter study. MATERIALS AND METHODS: Inclusion criteria are Parkinsonism with OAB symptoms for 4 weeks or more, OAB symptom score (OABSS) questionnaire scores greater than 2, and OABSS urgency question scores greater than 1. After a 2-week wash-out period, the patients were randomized into placebo and mirabegron groups at visit 2. Visit 3 was performed after 4 weeks of medication. Mirabegron was prescribed to the two groups for the rest of the study period at visit 4. RESULT: The mean age was 68.1 ± 8.1 years and 72 males and 64 females were included. A total of 136 patients were screened, 117 patients were randomized, and 25 patients dropped out. The OABSS scores were significantly different between the two groups at Weeks 4 and 8. The OABSS scores became the same in the two groups at Week 12 (visit 5). The postvoid residual urine volume showed a mild increase to 64 ml in the mirabegron group compared to the placebo group at visit 4. Adverse events occurred in 27 patients (23.1%). The degree was mild in 26 cases (78.8%), moderate in five (15.2%), and severe in two (6.1%). Only 13 cases (39.4%) showed medication-related adverse events. Acute urinary retention occurred in a single case. The treatment satisfaction questionnaires showed no significant differences between the two groups. CONCLUSION: Mirabegron was effective in treating OAB symptoms in patients with Parkinsonism with acceptable adverse events.

Au-Ag assembled on silica nanoprobes for visual semiquantitative detection of prostate-specific antigen.

BACKGROUND: Blood prostate-specific antigen (PSA) levels are widely used as diagnostic biomarkers for prostate cancer. Lateral-flow immunoassay (LFIA)-based PSA detection can overcome the limitations associated with other methods. LFIAbased PSA detection in clinical samples enables prognosis and early diagnosis owing to the use of high-performance signal reporters. RESULTS: Here, a semiquantitative LFIA platform for PSA detection in blood was developed using Au-Ag nanoparticles (NPs) assembled on silica NPs (SiO2@Au-Ag NPs) that served as signal reporters. Synthesized SiO2@Au-Ag NPs exhibited a high absorbance at a wide wavelength range (400-800 nm), with a high scattering on nitrocellulose membrane test strips. In LFIA, the color intensity of the test line on the test strip differed depending on the PSA concentration (0.30-10.00 ng/mL), and bands for the test line on the test strip could be used as a standard. When clinical samples were assessed using this LFIA, a visual test line with particular color intensity observed on the test strip enabled the early diagnosis and prognosis of patients with prostate cancer based on PSA detection. In addition, the relative standard deviation of reproducibility was 1.41%, indicating high reproducibility, and the signal reporter showed good stability for 10 days. CONCLUSION: These characteristics of the signal reporter demonstrated the reliability of the LFIA platform for PSA detection, suggesting potential applications in clinical sample analysis.

Favorable intermediate risk prostate cancer with biopsy Gleason score of 6.

BACKGROUND: To identify potential prognostic factors among patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6. METHODS: From 2003 to 2019, favorable intermediate risk patients who underwent radical prostatectomy were included in this study. All patients were evaluated preoperatively with MRI. Using PI-RADS scores, patients were divided into two groups, and clinic-pathological outcomes were compared. The impact of preoperative factors on significant pathologic Gleason score upgrading (≥ 4 + 3) and biochemical recurrence were assessed via multivariate analysis. Subgroup analysis was performed in patients with PI-RADS ≤ 2. RESULTS: Among the 239 patients, 116 (48.5%) were MRI-negative (PI-RADS ≤ 3) and 123 (51.5%) were MRI-positive (PI-RADS > 3). Six patients in the MRI-negative group (5.2%) were characterized as requiring significant pathologic Gleason score upgrading compared with 34 patients (27.6%) in the MRI-positive group (p < 0.001). PI-RADS score was shown to be a significant predictor of significant pathologic Gleason score upgrading (OR = 6.246, p < 0.001) and biochemical recurrence (HR = 2.595, p = 0.043). 10-years biochemical recurrence-free survival was estimated to be 84.4% and 72.6% in the MRI-negative and MRI-positive groups (p = 0.035). In the 79 patients with PI-RADS ≤ 2, tumor length in biopsy cores was identified as a significant predictor of pathologic Gleason score (OR = 11.336, p = 0.014). CONCLUSIONS: Among the patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6, preoperative MRI was capable of predicting significant pathologic Gleason score upgrading and biochemical recurrence. Especially, the patients with PI-RADS ≤ 2 and low biopsy tumor length could be a potential candidate to active surveillance.

Open Partial Nephrectomy vs. Robot-assisted Partial Nephrectomy for a Renal Tumor Larger than 4 cm: a Propensity Score Matching Analysis.

BACKGROUND: To compare open partial nephrectomy (OPN) and robot-assisted partial nephrectomy (RAPN) in the management of renal tumors larger than 4 cm. METHODS: Clinical records of 220 patients who underwent OPN or RAPN for a single renal tumor ≥ 4.0 cm with a normal contralateral kidney were reviewed. After determining the propensity score, surgical parameters, functional outcomes, and oncological outcomes were compared between OPN (n = 67) and RAPN (n = 67) groups of patients. RESULTS: The RAPN group had longer operation time (149.0 min vs. 173.3 min, P = 0.030) and longer ischemic time (20.3 min vs. 29.4 min, P = 0.001), but shorter hospital stay (8.2 days vs 6.0 days, P = 0.001) than the OPN group. Estimated blood loss (P = 0.053), pain visual analog score at 1 day postoperatively (P = 0.194), and complications of grade III or higher (P = 0.403) were similar between OPN and RAPN groups. There was no radical conversion or positive surgical margin in either group. Mean change in 6-month estimated glomerular filtration rate was significantly better in the RAPN group (-8.2 vs. -3.1, P = 0.027). There was no statistical difference in recurrence-free survival (P = 0.970) or cancer-specific survival (P = 0.345) between the two groups. CONCLUSION: RAPN is a safe and feasible surgical modality comparable to OPN for managing renal tumors larger than 4 cm in terms of surgical, functional, and oncological outcomes.

Silver-Assembled Silica Nanoparticles in Lateral Flow Immunoassay for Visual Inspection of Prostate-Specific Antigen.

Prostate-specific antigen (PSA) is the best-known biomarker for early diagnosis of prostate cancer. For prostate cancer in particular, the threshold level of PSA <4.0 ng/mL in clinical samples is an important indicator. Quick and easy visual detection of the PSA level greatly helps in early detection and treatment of prostate cancer and reducing mortality. In this study, we developed optimized silica-coated silver-assembled silica nanoparticles (SiO2@Ag@SiO2 NPs) that were applied to a visual lateral flow immunoassay (LFIA) platform for PSA detection. During synthesis, the ratio of silica NPs to silver nitrate changed, and as the synthesized NPs exhibited distinct UV spectra and colors, most optimized SiO2@Ag@SiO2 NPs showed the potential for early prostate cancer diagnosis. The PSA detection limit of our LFIA platform was 1.1 ng/mL. By applying each SiO2@Ag@SiO2 NP to the visual LFIA platform, optimized SiO2@Ag@SiO2 NPs were selected in the test strip, and clinical samples from prostate cancer patients were successfully detected as the boundaries of non-specific binding were clearly seen and the level of PSA was <4 ng/mL, thus providing an avenue for quick prostate cancer diagnosis and early treatment.