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Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions: Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

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 17β-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.

Purpose: We evaluated the feasibility, safety, and learning curve of extraperitoneal single-port robot-assisted radical prostatectomy (SP-RARP) and introduced innovative surgical techniques to maintain the instrument positions during the procedures. Materials and Methods: A cohort of 100 patients underwent extraperitoneal SP-RARP at our institution from December 2021 to April 2023. The procedures were performed by an experienced urology surgeon utilizing two surgical techniques for dissecting the posterior aspect of the prostate—“changing instrument roles” and “using camera inversion”—to prevent positional shifts between the camera and instruments. Results: The mean operation time for SP-RARP was 93.58 minutes, and the mean console time was 65.16 minutes. The mean estimated blood loss during the procedures was 109.30 mL. No cases necessitated conversion to multi-port robot, laparoscopy, or open surgery, and there were no major complications during the hospital stay or in the short-term follow-up. Early outcomes of post-radical prostatectomy indicated a biochemical recurrence rate of 4.0% over a mean follow-up duration of 6.40 months, with continence and potency recovery rates of 92.3% and 55.8%, respectively. Analysis of the learning curve showed no significant differences in operation time, console time, and positive surgical margin rates between the initial and latter 50 cases. Conclusions: Extraperitoneal SP-RARP is a feasible and safe option for the treatment of localized prostate cancer in skilled hands. Continued accrual of cases is essential for future comparisons of SP-RARP with multiport approaches.

Abstract To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54–1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83–1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10–30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

Abstract This study aimed to identify somatic mutations in nontumor cells (NSMs) in normal prostate and benign prostatic hyperplasia (BPH) and to determine their relatedness to prostate cancer (PCA). From 22 PCA patients, two prostates were sampled for 3-dimensional mapping (50 normal, 46 BPH and 1 PCA samples), and 20 prostates were trio-sampled (two normal or BPH samples and one PCA sample) and analyzed by whole-genome sequencing. Normal and BPH tissues harbored several driver NSMs and copy number alterations (CNAs), including in FOXA1, but the variations exhibited low incidence, rare recurrence, and rare overlap with PCAs. CNAs, structural variants, and mutation signatures were similar between normal and BPH samples, while BPHs harbored a higher mutation burden, shorter telomere length, larger clone size, and more private NSMs than normal prostates. We identified peripheral-zonal dominance and right-side asymmetry in NSMs, but the asymmetry was heterogeneous between samples. In one normal prostate, private oncogenic RAS-signaling NSMs were detected, suggesting convergence in clonal maintenance. Early embryonic mutations exhibited two distinct distributions, characterized as layered and mixed patterns. Our study identified that the BPH genome differed from the normal prostate genome but was still closer to the normal genome than to the PCA genome, suggesting that BPH might be more related to aging or environmental stress than to tumorigenic processes.

Background: DNA methylation markers are considered robust diagnostic features in various cancer types, as epigenetic marks are commonly altered during cancer progression. Differentiation between benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PCa) is clinically difficult, relying on the information of the patient's symptoms or levels of prostate-specific antigen. Methods: A total of 42 PCa patients and 11 BPH patients were recruited. Genomic DNA was purified from tissues and used for the library preparation of the target-enriched methylome with enzymatic conversion and a Twist 85 Mbp EM-seq panel. Paired-end sequencing (150 bp) was performed using NovaSeq 6000 or NextSeq 550. After quality control, including adapter trimming and de-duplication of raw sequencing data, differential methylation patterns were analyzed between the BPH and PCa groups. Results: We report DNA methylation patterns existing between BPH and PCa. The major finding is that broad hypermethylation occurred at genic loci in PCa tissues as compared to the BPH. Gene ontology analysis suggested that hypermethylation of genic loci involved in chromatin and transcriptional regulation is involved in cancer progression. We also compared PCa tissues with high Gleason scores to tissues with low Gleason scores. The high-Gleason PCa tissues showed hundreds of focal differentially methylated CpG sites corresponding to genes functioning in cancer cell proliferation or metastasis. This suggests that dissecting early-to-advanced-grade cancer stages requires an in-depth analysis of differential methylation at the single CpG site level. Conclusions: Our study reports that enzymatic methylome sequencing data can be used to distinguish PCa from BPH and advanced PCa from early-stage PCa. The stage-specific methylation patterns in this study will be valuable resources for diagnostic purposes as well as further development of liquid biopsy approaches for the early detection of PCa.

Abstract Objectives To systematically determine the diagnostic performance of each MRI feature of the PI-RADS for predicting extraprostatic extension (EPE) in prostate cancer. Methods A literature search in the MEDLINE and EMBASE databases was conducted to identify original studies reporting the accuracy of each feature on MRI for the dichotomous diagnosis of EPE. The meta-analytic pooled diagnostic odds ratio (DOR), sensitivity, specificity, and their 95% confidence intervals (CIs) were obtained using a bivariate random-effects model. Results After screening 1955 studies, 17 studies with a total of 3062 men were included. All six imaging features, i.e., bulging prostatic contour, irregular or spiculated margin, asymmetry or invasion of neurovascular bundle, obliteration of rectoprostatic angle, tumor-capsule interface > 10 mm, and breach of the capsule with evidence of direct tumor extension, were significantly associated with EPE. Breach of the capsule with direct tumor extension demonstrated the highest pooled DOR (15.6, 95% CI [7.7–31.5]) followed by tumor-capsule interface > 10 mm (10.5 [5.4–20.2]), asymmetry or invasion of neurovascular bundle (7.6 [3.8–15.2]), and obliteration of rectoprostatic angle (6.1 [3.8–9.8]). Irregular or spiculated margin showed the lowest pooled DOR (2.3 [1.3–4.2]). Breach of the capsule with direct tumor extension and tumor-capsule interface > 10 mm showed the highest pooled specificity (98.0% [96.2–99.0]) and sensitivity (86.3% [70.0–94.4]), respectively. Conclusions Among the six MRI features of prostate cancer, breach of the capsule with direct tumor extension and tumor-capsule interface > 10 mm were the most predictive of EPE with the highest specificity and sensitivity, respectively. Graphical abstract

Abstract Background Colorectal cancer survivors often experience decline in physical performance and poor quality of life after surgery and during adjuvant therapies. In these patients, preserving skeletal muscle mass and high-quality nourishment are essential to reduce postoperative complications and improve quality of life and cancer-specific survival. Digital therapeutics have emerged as an encouraging tool for cancer survivors. However, to the best of our knowledge, randomized clinical trials applying personalized mobile application and smart bands as a supportive tool to several colorectal patients remain to be conducted, intervening immediately after the surgical treatment. Methods This study is a prospective, multi-center, single-blinded, two-armed, randomized controlled trial. The study aims to recruit 324 patients from three hospitals. Patients will be randomly allocated to two groups for one year of rehabilitation, starting immediately after the operation: a digital healthcare system rehabilitation (intervention) group and a conventional education-based rehabilitation (control) group. The primary objective of this protocol is to clarify the effect of digital healthcare system rehabilitation on skeletal muscle mass increment in patients with colorectal cancer. The secondary outcomes would be the improvement in quality of life measured by EORTC QLQ C30 and CR29, enhanced physical fitness level measured by grip strength test, 30-sec chair stand test and 2-min walk test, increased physical activity measured by IPAQ-SF, alleviated pain intensity, decreased severity of the LARS, weight, and fat mass. These measurements will be held on enrollment and at 1, 3, 6 and 12 months thereafter. Discussion This study will compare the effect of personalized treatment stage-adjusted digital health interventions on immediate postoperative rehabilitation with that of conventional education-based rehabilitation in patients with colorectal cancer. This will be the first randomized clinical trial performing immediate postoperative rehabilitation in a large number of patients with colorectal cancer with a tailored digital health intervention, modified according to the treatment phase and patient condition. The study will add foundations for the application of comprehensive digital healthcare programs focusing on individuality in postoperative rehabilitation of patients with cancer. Trial registration NCT05046756. Registered on 11 May 2021.

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.

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.

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.

Abstract 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 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.

Abstract We aimed to identify the association between Hounsfield Unit(HU)-related variables and percutaneous nephrolithotomy (PCNL) outcomes. We enrolled patients with single renal stones (1–3 cm) who underwent single-tract PCNL between January 2014 and October 2019. Demographics and stone characteristics were retrospectively reviewed. Preoperative computerized tomography (CT) and follow-up CT within at least 3 months after PCNL were included in this analysis. Stone-free status was defined as residual stone measuring ≤ 2 mm within 3 months postoperatively. HU and cross-sectional area (CSA) were measured using the free-draw technique. We analyzed HU-related variables using logistic regression model for outcomes. Altogether, 188 out of 683 patients met the inclusion criteria. The stone-free rate (SFR) was 79.2%. There were no significant differences in age, sex, BMI, ASA class, laterality, pre-op shockwave lithotripsy, stone size, stone burden, skin-to-stone distance, and HU between the stone-free and remnant groups. CSA and HU/CSA in the stone-free and remnant groups were 94.5 ± 46.1 and 128.3 ± 98.5 (p = 0.043) and 10.1 ± 5.6 and 7.3 ± 3.4 (p = 0.001), respectively. Multivariate logistic regression analysis revealed that pelvis, ureteropelvic junction stones, and HU/CSA were independent predictors of SFR. HU did not affect PCNL outcomes. We believe that HU/CSA could be used for determining stone treatment plans and predicting outcomes.

Background: Robot-assisted laparoscopic prostatectomy (RALP) is a favored surgical approach for treating prostate cancer. However, RALP does not decrease postoperative pain significantly despite its minimal invasiveness. The pain associated with robot-assisted surgery is most severe during the immediate postoperative period. We aimed to demonstrate that preoperative rectus sheath block (RSB) can reduce acute pain after RALP. Methods: A prospective non-randomized study with two parallel groups was performed from June 2020 to August 2020. A total of 100 patients undergoing RALP were divided into two groups: the RSB group (n = 50) and the non-RSB group (n = 50). Ultrasound-guided RSB was performed preoperatively only in the RSB group. The primary outcome of the study was the visual analog scale (VAS) pain score during coughing (VAS-C) 1 h after surgery. In addition, the VAS pain score at rest (VAS-R) and the VAS-C were assessed up to 24 h after surgery. The doses of postoperative opioids consumed were also recorded. Results: The RSB group had a significantly lower VAS-C 1 h after RALP (58 [47–73] vs. 74 [63–83] mm, p = 0.001). In addition, the RSB group had significantly lower VAS-R and VAS-C scores, and postoperative opioid requirement, up to 6 h after surgery compared to the non-RSB group. Moreover, the VAS-R was significantly lower in the RSB group than in the non-RSB group 24 h after surgery. Conclusion: Preoperative RSB significantly improved analgesia during the early period after RALP. The long-term analgesic efficacy of RSB needs further study.

Purpose: To assess the safety and effect of the multifocal low-intensity extracorporeal shockwave therapy (MESWT) in the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: We randomly separated 30 patients with CP/CPPS into a MESWT and placebo group of same number using prospective-randomized, double-blind design. The participants’ National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total and subdomain scores, International Prostate Symptom Score (IPSS), International Index of Erectile Function-5 (IIEF-5), and visual analogue scale (VAS) were assessed and compared at baseline and at finishing immediately and 4 weeks after procedure and also were compared between MESWT and placebo group. Results: A total of 30 participants were randomized a MESWT or placebo group. Twenty of thirty participants completed this trial. NIH-CPSI total and subdomain scores, IPSS, IIEF-5, and VAS had significantly ameliorated compared with baseline in the MESWT group at 4 weeks assessment. Furthermore, comparison of the results from MESWT and placebo groups represented statistically significant differences in NIH-CPSI total and subdomain scores, IPSS, IIEF-5, and VAS. No side effects or events were occurred in both groups of the participants during study periods. Conclusions: MESWT can be an effective treatment modality in patients with CP/CPPS as it improves pain and QoL.

Background Patients with gastric cancer often encounter impaired quality of life and reduced tolerability to adjuvant treatments after surgery. Weight preservation is crucial for the overall prognosis of these patients, and exercise and supplemental nutrition play the main role. This study is the first randomized clinical trial to apply personalized, treatment stage-adjusted digital intervention with wearable devices in gastric cancer rehabilitation intervention for 12 months, commencing immediately after surgery. Methods This is a prospective, multicenter, two-armed, randomized controlled trial and aims to recruit 324 patients from two hospitals. Patients will be randomly allocated to two groups for 1 year of rehabilitation, starting immediately after the operation: a personalized digital therapeutic (intervention) group and a conventional education-based rehabilitation (control) group. The primary objective is to clarify the effect of mobile applications and wearable smart bands in reducing weight loss in patients with gastric cancer. The secondary outcomes are quality of life measured by the EORTC-QLQ-C30 and STO22; nutritional status by mini nutrition assessment; physical fitness level measured by grip strength test, 30-s chair stand test and 2-min walk test; physical activity measured by IPAQ-SF; pain intensity; skeletal muscle mass; and fat mass. These measurements will be performed on enrollment and at 1, 3, 6, and 12 months thereafter. Conclusions Digital therapeutic programs include exercise and nutritional interventions modified by age, body mass index, surgery type and postoperative days. Thus, expert intervention is pivotal for precise and safe calibration of this program. Trial registration Clinicaltrials.gov identifier: NCT04907591 (registration date: June 11, 2020; https://clinicaltrials.gov/ct2/show/NCT04907591 ).

Purpose: There is no definite treatment method for chronic pelvic pain syndrome (CPPS). The purpose of this study was to compare and assess the effectiveness and safety of low-intensity extracorporeal shockwave therapy (Li-ESWT) versus placebo treatment in CPPS IIIb patients. Materials and Methods:Materials and Methods: Thirty participants with CPPS IIIb were included and randomized in this prospective, double-blind, placebo-controlled study. Li-ESWT was performed at the perineum without anesthesia once per week for 8 weeks. CPPS-related symptoms were evaluated using the National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI). Pain and erectile function were appraised using the Visual Analogue Scale (VAS) and International Index of Erectile Function-Erectile Function (IIEF-EF), respectively. The Global Efficacy Assessment Question (GEAQ) was also assessed. The parameters were evaluated immediately after the last Li-ESWT treatment and 4 weeks after Li-EWST treatment. Results:Results: Fifteen subjects each in the Li-ESWT and placebo groups completed this study. Amelioration of NIH-CPSI total, pain, and quality of life score in the Li-ESWT group was found compared to the placebo group (p=0.002, 0.02, 0.001, respec-tively). Improvement of the VAS score was observed in the Li-ESWT group (p=0.002). The differences in the GEAQ “Yes” re-sponses were also significant in the Li-ESWT group. No patients experienced side effects related to ESWT during therapeutic period or follow-up duration. Conclusions:Conclusions: Results indicated that Li-ESWT improved the NIH-CPSI score, pain, and the quality of life in CPPS IIIb patients. Li-ESWT could be an effective alternative treatment modality for CPPS IIIb.

Objectives: Big data-based multicenter medical research is expected to bring significant advances to cancer treatment worldwide. However, there are concerns related to data sharing among multicenter networks. Clinical data can be shielded by firewalls using distributed research networks (DRNs). We attempted to develop DRNs for multicenter research that can be easily installed and used by any institution. Patients and Methods: We propose a DRN for multicenter cancer research called the cancer research line (CAREL) and present a data catalog based on a common data model (CDM). CAREL was validated using 1723 patients with prostate cancer and 14 990 patients with lung cancer in a retrospective study. We used the attribute-value pairs and array data type JavaScript object notation (JSON) format to interface third-party security solutions such as blockchain. Results: We developed visualized data catalogs of prostate and lung cancer based on the observational medical outcomes partnership (OMOP) CDM, from which researchers can easily browse and select relevant data. We made the CAREL source code readily available for download and application for relevant purposes. In addition, it is possible to realize a multicenter research network using CAREL development sources. Conclusion: CAREL source can enable medical institutions to participate in multicenter cancer research. Our technology is open source, so small institutions that cannot afford to spend high costs can use it to develop a platform for multicenter research.

Objectives: To efficiently implement artificial intelligence (AI) software for medical applications, it is crucial to understand the acceptance, expected effects, expected performance, and concerns of software users. In this study, we examine the acceptance and expectation of the Dr. Answer AI software for prostate cancer. Methods: We conducted an online survey for urologists from August 13 to September 18, 2020. The target software is an AI-based clinical software called Dr. Answer AI software, used for prostate cancer diagnosis. We collected data from 86 urologists and conducted a basic statistical and multiple regression analysis using the R package. Results: The compatibility was significantly associated with the intention to use the Dr. Answer AI software. The expected average accuracy for the software ranges from 86.91% to 87.51%, and the urologists perceived that the cloud method is suitable to introduce the software. The most desirable function of the software for the specialists is predicting the occurrence of extracapsular extension, seminal vesicle invasion, and lymph node metastasis after radical prostatectomy. Finally, the primary concerns involved the cost, compatibility with existing systems, and obtaining accurate information from the software. Conclusions: Our results present an understanding of the acceptance, expected effects, expected performance, and concerns of software users. The results provide a guide to help AI software be properly developed and implemented in medical applications.

Purpose: Robot-assisted radical cystectomy (RARC) optimizes patient recovery and has outcomes comparable with those of open surgery. This study aimed to compare the perioperative and oncologic outcomes of RARC in female and male patients. Materials and Methods: A retrospective cohort study of the Korean Robot-Assisted Radical Cystectomy Study Group database from 2007 to 2019 identified 749 patients (111 females and 638 males). Female were matched 1:1 to male by propensity score matching using a logistic regression. We compared perioperative outcomes, oncologic outcomes, and complications between the two groups. Results: The female group had comparable perioperative outcomes to the male group in terms of operation time, lymph node yield, positive surgical margin, blood transfusion rate, and hospitalization days. Complication rate and grade were not significantly different between the two groups. The most common complication was infection in female and gastrointestinal complications in male. We compared the 5-year overall, disease-specific, and recurrence-free survival of female and male: 58.2% vs. 68.0% (p=0.495), 75.7% vs. 79.3% (p=0.645), and 40.8% vs. 53.5% (p=0.913), respectively. On multivariable analysis, T stage (>T2), postoperative complications, and positive surgical margin were prognostic factors of poor outcome. Sex was not an independent predictor of the three survivals. Conclusions: The current study suggests that RARC in female has comparable perioperative and oncologic outcomes to those in male. The complication rate of RARC in female was comparable to that in male, but the type of complications differed by sex.

Background: The purpose of this study was to determine the influence of preoperative factors on the recovery of continence after artificial urinary sphincter (AUS) implantation in postprostatectomy incontinence. Materials and methods: Seventy-two patients who underwent AUS implantation between April 2006 and March 2020 were analyzed. The clinical features and preoperative urodynamic parameters were correlated with the postoperative continence rate using linear and logistic regression analysis. The recovery of continence was defined by the patient requiring no use of a protective urine pad during the 24 hours. Results: Of the 72 patients, 57 (79.2%) recovered continence (dry group), while 15 (20.8%) were wearing more than 1 pad per day (wet group) on the last follow-up visit. In the clinical characteristics, only the interval between radical prostatectomy and AUS (in months) showed a statistically significant difference (35.4 ± 26.2 in the dry group, 22.7 ± 12.2 in the wet group, p = 0.009). Other preoperative clinical features such as the underlying disease, surgical methods, size of prostate, tumor stage, and radio nor hormonal therapy did not present statistically significant differences.Of the preoperative urodynamic parameters, only the abdominal leak point pressure (ALPP) showed statistical significance when related to surgical outcomes by 88.6 ± 33.6 in the dry group and 66.1 ± 29.6 in wet the group (P = 0.024). The number of patients for whom ALPP was higher than 80 cm H2O was 61.4% in the dry group and 20% in the wet group (95% confidence interval: 1.612-25.11). Other preoperative UDS features including detrusor underactivity, maximum urethral closure pressure, and others were not statistically significant. Conclusions: The interval between RP and AUS, as well as the preoperative ALPP, can be possible predictive factors for the surgical outcomes of AUS implantation. In addition, an ALPP of >80 cm H2O has a high degree of predictability for success of AUS surgical outcomes in post-RP incontinence.

Abstract 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.

Erectile dysfunction (ED) is a common and feared complication of radical prostatectomy (RP) for prostate cancer. Recently, tissue engineering for post-prostatectomy ED has been attempted in which controlled interactions between cells, growth factors, and the extracellular matrix (ECM) are important for the structural integrity if nerve regeneration. In this study, we evaluated the effects of a biomechanical ECM patch on the morphology and behavior of human bone marrow-derived mesenchymal stem cells (hBMSCs) in a bilateral cavernous nerve injury (BCNI) rat model. The ECM patch, made of decellularized human fibroblast-derived ECM (hFDM) and a biocompatible polyvinyl alcohol (PVA) hydrogel, was tested with human bone marrow-derived mesenchymal stem cells (hBMSCs) on a bilateral cavernous nerve injury (BCNI) rat model. In vitro analysis showed that the hFDM/PVA + hBMSCs patches significantly increased neural development markers. In vivo experiments demonstrated that the rats treated with the hFDM/PVA patch had higher ICP/MAP ratios, higher ratios of smooth muscle to collagen, increased nNOS content, higher levels of eNOS protein expression, and higher cGMP levels compared to the BCNI group. These results indicate that the hFDM/PVA patch is effective in promoting angiogenesis, smooth muscle regeneration, and nitrergic nerve regeneration, which could contribute to improved erectile function in post-prostatectomy ED.

Abstract Predicting the risk of metastasis before starting prostate cancer (PCa) treatment can minimize the overtreatment of indolent cases and help choosing appropriate treatment. The levels of circulating microRNAs (miRNAs) from body fluids can be used as noninvasive prognostic biomarkers. In this study, urinary exosomal miRNA expression profiles of 149 PCas were determined and the miRNAs associated with metastasis were identified: miR-21, miR-16, miR-142-3p, miR-451, and miR-636. When evaluating clinical factors together, miR-21, miR-451, miR-636, and preoperative prostate-specific antigen (PSA) level remained significant in the multivariate analysis. Based on them, we developed a “Prostate Cancer Metastasis Risk Scoring (PCa-MRS)” model. The PCa-MRS showed superior stratification power (AUC = 0.925) to preoperative PSA or clinical Gleason score. Patients with high scores showed significantly poorer biochemical recurrence-free survival than those with low scores (P = 6.53 × 10−10). Our results showed the potential of urinary exosomal miRNAs as noninvasive markers for predicting metastasis and prognosis in PCa patients.

Abstract This study aimed to investigate the effect of intraoperative fluid volume on the postoperative ileus (POI) recovery period. A retrospective review of the Korean robot-assisted radical cystectomy database identified 718 patients who underwent robot-assisted radical cystectomy (RARC). Regression analyses were performed to identify the associations between the amount of intraoperative fluid administration (crystalloid/colloid/total), POI period (time to flatus/bowel movements), and length of hospital stay (LOS) after adjusting for covariates. In addition, we analyzed the risk factors for gastrointestinal complications and prolonged POI using a logistic regression model. An increasing volume of the administered crystalloid/total fluid was associated with prolonged POI (crystalloid R2 = 0.0725 and P

APOBEC3B enzymes are endogenous carcinogenic mutagens. Metastatic urothelial carcinomas often harbor APOBEC3B-mediated mutations in which tCw to T or G substitution occurs. Here, we evaluated patient survival and CD8+ T-cell density according to APOBEC3B expression in patients with metastatic urothelial carcinoma who underwent cytotoxic chemotherapy. We performed a retrospective study on 94 patients with urothelial carcinoma who were treated with first line palliative chemotherapy. APOBEC3B expression and CD8+/CD3+ ratio of tumor-infiltrating lymphocytes were evaluated using immunohistochemistry. Kaplan–Meier survival curves were generated and the log-rank test was employed. The association between APOBEC3B expression and tumor-infiltrating lymphocytes was analyzed using Pearson’s chi-squared test. High APOBEC3B expression was detected in 71 of the 94 patients (75.5%). The median overall survival was longer in patients with high APOBEC3B expression (15 months) than in those with low expression (p = 0.045). The hazard ratio obtained based on the Cox regression analysis was 0.292 (95% confidence interval 0.118–0.723, p = 0.008). APOBEC3B expression was associated with the CD8+/CD3+ ratio (2.914, 95% confidence interval 1.030–8.249, p = 0.039). Collectively, APOBEC3B expression was an independent prognostic factor in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy. Tumor-infiltrating cytotoxic T cells were associated with APOBEC3B expression.

Abstract MicroRNAs (miRNAs) of urine exosomes have emerged as biomarkers for urological cancers, owing to their high stability. MiRNAs have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence (BCR) and metastasis. In this study, we aimed to identify urinary exosomal miRNAs as prognostic markers associated with BCR in intermediate-risk prostate cancer. We profiled the expression levels of miRNAs via next generation sequencing in urinary exosomes from 21 non-BCR patients and 6 BCR patients of intermediate-risk prostate cancer. A total of 21 urinary exosomal miRNAs were found to be differentially expressed (> twofold) in BCR patients compared to non-BCR patients. For external validation, we validated these results using quantitative reverse transcription PCR in an independent cohort of 28 non-BCR patients and 26 BCR patients. A validation analysis revealed that three miRNAs (miR-26a-5p, miR-532-5p, and miR-99b-3p) were upregulated in exosomes from BCR patients. The univariate and multivariate Cox regression analyses showed that miR-532-5p was an important predictive factor for BCR of intermediate-risk prostate cancer. In conclusion, miR-532-5p in urine exosomes might be a potential biomarker for predicting BCR, which is a poor prognosis in patients with intermediate-risk prostate cancer. Further research is needed on the biological functions and mechanisms of this miRNA.

Purpose: Prostate cancer has a low mortality rate and requires persistent treatment; however, treatment decisions are challenging. Because prostate cancer is complex, the outcomes warrant thorough follow-up evaluation for appropriate treatment. Electronic health records (EHRs) do not present intuitive information. This study aimed to develop a Clinical Decision Support System (CDSS) for prognosis management of radical prostatectomy. Methods: We used data from 5,199 prostate cancer patients from three hospitals’ EHRs in South Korea, comprising laboratory results, surgery, medication, and radiation therapy. We used open source R for data preprocessing and development of web-based visualization system. We also used R for automatic calculation functionalities of two factors to visualize the data, e.g., Prostate-Specific Antigen Doubling Time (PSADT), and four Biochemical Recurrence (BCR) definitions: American Society of Therapeutic Radiology and Oncology (ASTRO), Phoenix, consecutive PSA > 0.2 ng/mL, and PSA > 0.2 ng/mL. Results: We developed the Prostate Cancer Trajectory Map (PCT-Map) as a CDSS for intuitive visualization of serial data of PSA, testosterone, surgery, medication, radiation therapy, BCR, and PSADT. Conclusions: The PCT-Map comprises functionalities for BCR and PSADT and calculates and visualizes the newly added patient data automatically in a PCT-Map data format, thus optimizing the visualization of patient data and allowing clinicians to promptly access patient data to decide the appropriate treatment.

Purpose: The purpose of this study was to evaluate end-of-life resource utilization and costs for prostate cancer patients during the last year of life in Korea. Materials and Methods: The study used the National Health Information Database (NHIS-2017-4-031) of the Korean National Health Insurance Service. Healthcare claim data for the years 2002 through 2015 were collected from the Korean National Health Insurance System. Among 83,173 prostate cancer patients, we enrolled 18,419 after excluding 1,082 who never claimed for the last year of life. Results: From 2006 to 2015, there was a 3.2-fold increase the total number of prostate cancer decedents. The average cost of care during the last year of life increased over the 10-year period, from 14,420,000 Korean won to 20,300,000 Korean won, regardless of survival time. The cost of major treatments and medications, other than analgesics, was relatively high. Radiologic tests, opioids, pain control, and rehabilitation costs were relatively low. Multiple regression analysis identified age and living in rural area as negatively associated with prostate cancer care costs, whereas income level and a higher number of comorbidities were positively associated. Conclusions: Expenditure of prostate cancer care during the last year of life varied according to patient characteristics. Average costs increased every year. However, the results suggest underutilization of support services, likely due to lack of alternative accommodation for terminal prostate cancer patients. Further examination of patterns of utilization of healthcare resources will allow policymakers to take a better approach to reducing the burden of prostate cancer care.

Abstract 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.

Purpose: Chronic prostatitis (CP), including chronic pelvic pain syndrome (CPPS), is the most commonly encountered manifestation of prostatitis. The aim of this study was to evaluate the effect of electric stimulation hyperthermia treatment (ESHT) on CP/CPPS and to explore the underlying mechanism. Materials and Methods: RWPE-2 cells with lipopolysaccharide-induced inflammation and a prostatitis rat model induced by 17β-estradiol and dihydrotestosterone underwent sham, electric stimulation, or ESHT treatment. Four weeks later, cells, supernatants, and rat prostates were collected for analysis using immunohistochemistry, Western blots, and enzyme-linked immunosorbent assays. Results: We found that ESHT improved prostatitis in vivo and attenuated inflammation in vitro. ESHT significantly induced suppressor of cytokine signaling 3 (SOCS3) expression and subsequently promoted HSP70. It attenuated inflammation through decreased expression of toll-like receptor 4 (TLR4), nuclear factor kappa B, and subsequent inflammatory cytokines. ESHT also inhibited apoptosis and released growth factor in tissue affected by prostatitis. Conclusions: ESHT improved CP/CPPS and reversed pathologic changes of prostatitis by inhibiting the SOCS3-TLR4 pathway.

Purpose: The aim of the present study was to evaluate the efficacy and safety of the electromagnetic-type low-intensity extracorporeal shock wave therapy (Li-ESWT) in patients with erectile dysfunction (ED). Materials and Methods: The randomized, sham-controlled, double-blind prospective study was performed at two referral hospitals. Participants were randomized in a 1:1 ratio to receive sham or Li-ESWT for 6 weeks. ED was evaluated at screening and at 4 and 7 weeks after treatment. Participants were asked to complete the international index of erectile function-erectile function (IIEF-EF) domain questionnaire, erection hardness scale (EHS), and sexual encounter profile questionnaire (SEPQ 2 and 3). The development of complications was investigated. Results: Eighty-one of 96 patients completed the study. The median change in the IIEF-EF score in the Li-ESWT and sham groups was 5.1 and -2.2 (p

Abstract 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.

Digital pathology (DP) is no longer an unfamiliar term for pathologists, but it is still difficult for many pathologists to understand the engineering and mathematics concepts involved in DP. Computer-aided pathology (CAP) aids pathologists in diagnosis. However, some consider CAP a threat to the existence of pathologists and are skeptical of its clinical utility. Implementation of DP is very burdensome for pathologists because technical factors, impact on workflow, and information technology infrastructure must be considered. In this paper, various terms related to DP and computer-aided pathologic diagnosis are defined, current applications of DP are discussed, and various issues related to implementation of DP are outlined. The development of computer-aided pathologic diagnostic tools and their limitations are also discussed.

Purpose: This study aimed to compare complications, perioperative parameters, and oncologic outcomes between robot-assisted radical cystectomy (RARC) with extracorporeal urinary diversion (ECUD) and RARC with intracorporeal urinary diversion (ICUD). Materials and Methods: Between 2007 and 2017, 362 patients who underwent RARC with ECUD or ICUD at multiple tertiary referral institutions were assessed. The primary endpoints were complication rates. The secondary outcomes were perioperative recovery parameters and oncological outcomes including estimated recurrence-free survival (RFS) and recurrence pattern between the 2 groups. Additionally, the complication rates of 2 expert surgeons with experience of >100 RARCs were analyzed. Results: The ICUD group showed lower overall, gastrointestinal, and genitourinary complications (p=0.001, p=0.036, and p=0.036, respectively) than the ECUD group. Concerning perioperative outcomes, the ICUD group had a significantly longer operation time (p=0.002), although recovery parameters such as time to flatus passage, oral intake, and length of hospital stay were significantly shorter in this group (p=0.001, p

Purpose: This study aimed to evaluate the clinical efficacy of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients using real-world data from Korean patients. Materials and Methods: We retrospectively reviewed the medical records of 199 chemotherapy-naïve patients with mCRPC at 13 tertiary centers in Korea between 2014 and 2017. All patients received enzalutamide daily and 89 patients received concurrent androgen deprivation therapy (ADT). Results: The median age of the patients was 74 years. Initial results showed that 81.5% of the patients had Gleason score ≥8 and 33.3% of the patients had European Cooperative Oncology Group Performance Status 0. The overall mortality rate was 12%. The median OS was not archieved and 76.7% of patients were alive at 30 months. Median time until PSA progression was 6 months. The overall survival rate at 2 years was significantly higher (84.6% vs. 71.7%, p=0.015) and the duration of PSA progression-free survival was significantly longer (8.0 vs. 4.6 months, p=0.008) in patients receiving concurrent ADT than in those receiving enzalutamide alone. The incidence of adverse events of grade 3 or higher was 1.7%. Multivariate Cox proportional hazard analysis indicated that ADT administered concurrently with enzalutamide significantly improved the overall survival (hazard ratio, 0.346; 95% confidence interval, 0.125–0.958). Conclusions: Enzalutamide is effective and safe for chemotherapy-naïve patients with mCRPC. Furthermore, the overall survival was significantly higher in patients receiving enzalutamide and concurrent ADT than in patients receiving enzalutamide alone.

[This corrects the article DOI: 10.1371/journal.pone.0249709.].

Objectives: To develop a model to predict biochemical recurrence (BCR) after radical prostatectomy (RP), using artificial intelligence (AI) techniques. Patients and Methods: This study collected data from 7,128 patients with prostate cancer (PCa) who received RP at 3 tertiary hospitals. After preprocessing, we used the data of 6,755 cases to generate the BCR prediction model. There were 16 input variables with BCR as the outcome variable. We used a random forest to develop the model. Several sampling techniques were used to address class imbalances. Results: We achieved good performance using a random forest with synthetic minority oversampling technique (SMOTE) using Tomek links, edited nearest neighbors (ENN), and random oversampling: accuracy = 96.59%, recall = 95.49%, precision = 97.66%, F1 score = 96.59%, and ROC AUC = 98.83%. Conclusion: We developed a BCR prediction model for RP. The Dr. Answer AI project, which was developed based on our BCR prediction model, helps physicians and patients to make treatment decisions in the clinical follow-up process as a clinical decision support system.

Purpose: We investigated the synergy effect of extracorporeal shock wave therapy (ESWT) with modified Ojayeonjonghwan (Korean herbal formula, KH-204) in an animal model of diabetes mellitus (DM)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male Sprague-Dawley rats were used in this study. DM was induced by an intraperitoneal injection of streptozotocin. DM rats were divided into 5 groups (n=10 per group): group 1, control; group 2, DM; group 3, DM+ESWT; group 4, DM+KH-204; and group 5, DM+ESWT+KH-204. In ESWT groups, rats were treated with ESWT at the penis 3 times a week for 2 weeks under anesthesia. The KH-204 groups were treated with a daily oral dose of KH-204 for 12 weeks. After all treatments, intracavernosal pressure (ICP) was measured, and the cavernous tissues were evaluated by Masson's trichrome, immunohistochemistry and western blot analysis. Results: ICP was evaluated as a measurement of erectile function. The DM+ESWT, DM+KH-204, and DM+ESWT+KH-204 groups showed significantly restored erectile function compared with the DM group (p

Abstract Background A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service. Methods Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated. Results From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter. Conclusions Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.

The Asian Prostate Cancer (A-CaP) study is an Asia-wide initiative that was launched in December 2015 in Tokyo, Japan, with the objective of surveying information about patients who have received a histopathological diagnosis of prostate cancer (PCa) and are undergoing treatment and clarifying distribution of staging, the actual status of treatment choices, and treatment outcomes. The study aims to clarify the clinical situation for PCa in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo in December 2015, the second A-CaP meeting was held in Seoul, Korea, in September 2016. This, the third A-CaP meeting, was held on October 14, 2017, in Chiang Mai, Thailand, with the participation of members and collaborators from 12 countries and regions. In the meeting, participating countries and regions presented the current status of data collection, and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data input and collection, institutional, and legislative issues that may present barriers to data sharing, and the outlook for further patient registrations through to the end of the registration period in December 2018. In addition to A-CaP–specific discussions, a series of special lectures were also delivered on the situation for health insurance in the United States, the correlation between insurance coverage and PCa outcomes, and the outlook for robotic surgery in the Asia-Pacific region. Members also confirmed the principles of authorship in collaborative studies, with a view to publishing original articles based on A-CaP data in the future. Keywords: Asia, Cancer, Database, Prospective study, Prostate cancer, Registry

The hypersensitive prostate specific antigen (PSA) test can measure in 0.01 ng/mL units, and its efficacy for screening after radical prostatectomy (RP) has been reported. In this study, we assessed patients who underwent RP to evaluate whether the nadir value affects biochemical recurrence (BCR). From 1995 to 2014, patients classified as N0 who had negative resection margins and a nadir PSA of less than 0.2 ng/mL were evaluated. The characteristics, pathological outcomes, PSA after RP, and BCR were assessed. A total of 1483 patients were enrolled. Among them, 323 (21.78%) patients showed BCR after RP. The mean age of the BCR group was 63.86±7.31 years, and while that of the no-recurrence group was 64.06±6.82 years (P = 0.645). The mean preoperative PSA of the BCR group was 9.75±6.92 ng/mL and that of the no-recurrence group was 6.71±5.19 ng/mL (P < 0.001). The mean time to nadir (TTN) in the BCR group was 4.64±7.65 months, while that in the no-recurrence group was 7.43±12.46 months (P < 0.001). The mean PSA nadir value was 0.035±0.034 ng/mL in the BCR group and 0.014±0.009 ng/mL in the no-recurrence group (P < 0.001). In multivariable Cox regression analyses, Gleason score, positive biopsy core percentages, minimal invasive surgery, nadir PSA value, and TTN were independently associated with BCR. The mean BCR occurred at 48.23±2.01 months after RP, and there was a significant difference in BCR occurrence according to the nadir PSA value (P < 0.001). A high PSA nadir value and short TTN may predict the risk of BCR after successful RP, aiding the identification of candidates for adjuvant or salvage therapies after RP.

There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 (SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1 + ) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1 − ). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1 + , imMSCs/eSDF-1 − , or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1 + expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1 + improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1 + group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1 + group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1 + group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.

ObjectivesThe importance of clinical outcome prediction models using artificial intelligence (AI) is being emphasized owing to the increasing necessity of developing a clinical decision support system (CDSS) employing AI. Therefore, in this study, we proposed a "Dr. Answer" AI software based on the clinical outcome prediction model for prostate cancer treated with radical prostatectomy.MethodsThe Dr. Answer AI was developed based on a clinical outcome prediction model, with a user-friendly interface. We used 7,128 clinical data of prostate cancer treated with radical prostatectomy from three hospitals. An outcome prediction model was developed to calculate the probability of occurrence of 1) tumor, node, and metastasis (TNM) staging, 2) extracapsular extension, 3) seminal vesicle invasion, and 4) lymph node metastasis. Random forest and k-nearest neighbors algorithms were used, and the proposed system was compared with previous algorithms.ResultsRandom forest exhibited good performance for TNM staging (recall value: 76.98%), while k-nearest neighbors exhibited good performance for extracapsular extension, seminal vesicle invasion, and lymph node metastasis (80.24%, 98.67%, and 95.45%, respectively). The Dr. Answer AI software consisted of three primary service structures: 1) patient information, 2) clinical outcome prediction, and outcomes according to the National Comprehensive Cancer Network guideline.ConclusionThe proposed clinical outcome prediction model could function as an effective CDSS, supporting the decisions of the physicians, while enabling the patients to understand their treatment outcomes. The Dr. Answer AI software for prostate cancer helps the doctors to explain the treatment outcomes to the patients, allowing the patients to be more confident about their treatment plans.

Prostate cancer: Promising protein biomarker A protein found in high levels in prostate cancer tissues could provide a biomarker and therapeutic target for the disease. Prostate cancer (PCa) is a common cause of cancer-related death, yet existing biomarkers cannot reliably predict PCa risk. The search for a novel biomarker led Yeun-Jun Chung at the Catholic University of Korea in Seoul, South Korea, and co-workers to examine the role of the trefoil factor family 3 (TFF3) protein. TFF3 overexpression is implicated in tumor invasion and in limiting tumor cell death in many cancers, including PCa. Chung’s team analyzed TFF3 levels in 108 cases of PCa and found they were significantly higher than in normal prostate tissues. Blocking the overexpression of TFF3 in two PCa cell lines limited tumor cell growth and migration, and increased cancer cell death.