Single-Port Versus Multi-Port Robotic Retroperitoneal Partial Nephrectomy: A Propensity Score-Matched Comparison.

Objective: To compare the surgical results of retroperitoneal (RP) robot partial nephrectomy (PNx) using either a single-port robot (SP) or a multi-port robot (MP). Materials and Methods: We retrospectively reviewed all RP robotic PNx performed at a single institution from September 2021-when the SP robot was introduced to the institution-through April 2023. In total, 125 patients underwent the surgery; 81 patients were treated with surgery using a MP robot whereas 44 patients were treated with surgery using a SP. All MP surgeries were performed with da Vinci Xi (Intuitive, Sunnyvale, California, USA), while all SP surgeries were performed with da Vinci SP (Intuitive, Sunnyvale, California, USA). We performed a propensity score-matching (PSM) analysis of these 125 patients. Results: There was no significant difference between the two groups after PSM. In terms of operation time, that for MP was 103.68 ± 21.89 minutes whereas that for SP was 95.43 ± 32.22 minutes (p-value = 0.164). Meanwhile, in terms of console time, that for MP was 70.95 ± 21.92 minutes whereas that for SP was 64.14 ± 32.06 minutes (p-value = 0.248). In terms of estimated blood loss was 90.91 ± 91.06 mL in MP and 92.27 ± 104.30 mL in SP (p-value = 0.948). Lastly, there was a statistically significant difference in warm ischemic time, as it was 17.18 ± 6.56 minutes in MP and 13.82 ± 4.59 in SP (p-value = 0.007). There were no statistically significant differences between MP and SP in any other surgical outcomes. Conclusions: SP robot RP PNx demonstrated comparable outcomes to those achieve using MP procedures. This means SP robot RP PNx can be considered a preferable and more convenient surgical approach than conventional methods, particularly when dealing with small renal masses located in the posterior side of the kidney.

Extraperitoneal single-port robot-assisted radical prostatectomy: Short-term outcomes and technique description.

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.

Exosomal miR-664a-5p as a therapeutic target biomarker for PARP inhibitor response in prostate cancer.

This study investigated the role of urinary exosomal miR-664a-5p as a potential therapeutic target in prostate cancer (PCa). Small RNA sequencing of urinary exosomes from PCa patients with different responses to PARP inhibitors revealed that miR-664a-5p was significantly upregulated in responsive patients. Overexpression of miR-664a-5p enhanced the sensitivity of PCa cells to PARP inhibitors by directly targeting FOXM1, a transcription factor involved in DNA damage repair, leading to the downregulation of DNA damage response genes. Combined treatment with miR-664a-5p and olaparib synergistically inhibited tumor growth in a PC-3 xenograft mouse model. These findings suggest that urinary exosomal miR-664a-5p is a potential therapeutic biomarker for PARP inhibitor response in PCa patients, and targeting FOXM1 via miR-664a-5p represents a promising strategy for enhancing PARP inhibitor efficacy in PCa treatment.

Intrathecal Morphine Enhances Postoperative Analgesia and Recovery in Robotic-Assisted Laparoscopic Partial Nephrectomy: A Retrospective Study of 272 Patients.

BACKGROUND Robot-assisted laparoscopic partial nephrectomy (RAPN) has been increasingly used for treating renal tumors due to its advantages over other approaches. However, RAPN can induce acute incisional, peritoneal, visceral, and referred pain. Therefore, acute pain control in robotic surgery is a concern. This retrospective study aimed to evaluate the efficacy of intrathecal morphine (ITM) for postoperative analgesia and recovery after RAPN. MATERIAL AND METHODS We retrospectively investigated consecutive patients who underwent RAPN at our institute between 2020 and 2021. Among the 272 patients who met the inclusion criteria, 135 patients were administered 200 µg of ITM preoperatively (ITM group), while 137 patients were not (control group). Postoperative pain assessments using the numeric rating scale (NRS), opioid requirements, and recovery profiles during the first postoperative 24 h were compared between the 2 groups. RESULTS As the primary endpoint, the incidence of moderate-to-severe pain (24-h average NRS pain score ≥4) was significantly lower in the ITM group than in the control group (36.3% vs 61.3%, P<0.001). Pain scores and cumulative opioid requirements were also significantly lower in the ITM group for all assessments (P<0.001). Moreover, the ITM group had a higher score on the Quality of Recovery-15 questionnaire on the first postoperative day (129 vs 120, P=0.003) despite an increased rate of postoperative nausea/vomiting (27.4% vs 13.1%, P=0.003). CONCLUSIONS Our findings indicate that ITM provided superior pain control during the early period following RAPN, with reduced postoperative opioid requirements. Moreover, ITM improved patient satisfaction with recovery.

Pre-Op Hydronephrosis Predicts Outcomes in Patients Receiving Robot-Assisted Radical Cystectomy.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) has gained momentum in the management of muscle invasive bladder cancer (MIBC). Predictors of RARC outcomes are not thoroughly studied. We aim to investigate the implications of preoperative hydronephrosis on oncological outcomes. PATIENTS AND METHODS: This study analysed data from the Asian RARC consortium, a multicentre registry involving nine Asian centres. Cases were divided into two groups according to the presence or absence of pre-operative hydronephrosis. Background characteristics, operative details, perioperative outcomes, and oncological results were reviewed. Outcomes were (1) survival outcomes, including 10-year disease-free survival (DFS) and overall survival (OS), and (2) perioperative and pathological results. Multivariate regression analyses were performed on survival outcomes. RESULTS: From 2007 to 2020, 536 non-metastatic MIBC patients receiving RARC were analysed. 429 had no hydronephrosis (80.0%), and 107 (20.0%) had hydronephrosis. Hydronephrosis was found to be predictive of inferior DFS (HR = 1.701, p = 0.003, 95% CI = 1.196-2.418) and OS (HR = 1.834, p = 0.008, 95% CI = 1.173-2.866). Subgroup analysis demonstrated differences in the T2-or-above subgroup (HR = 1.65; p = 0.004 in DFS and HR = 1.888; p = 0.008 in OS) and the T3-or-above subgroup (HR = 1.757; p = 0.017 in DFS and HR = 1.807; p = 0.034 in OS). CONCLUSIONS: The presence of preoperative hydronephrosis among MIBC patients carries additional prognostic implications on top of tumour staging. Its importance in case selection needs to be highlighted.

A preoperative scoring system for predicting the extraprostatic extension of prostate cancer following radical prostatectomy using magnetic resonance imaging and clinical factors.

PURPOSE: We aimed to develop a preoperative prediction model for extraprostatic extension (EPE) in prostate cancer (PCa) patients following radical prostatectomy (RP) using MRI and clinical factors. METHODS: This retrospective study enrolled 266 consecutive patients who underwent RP for PCa in 2022. These patients were divided into a training set (n = 187) and a test set (n = 79) through random assignment. The evaluated variables included age, prostate-specific antigen (PSA) level, prostate volume, PSA density (PSAD), index tumor length on MRI, Prostate Imaging-Reporting and Data System (PI-RADS) category, and EPE-related MRI features as defined by PI-RADS v2.1. A predictive model was constructed through multivariable logistic regression and subsequently translated into a scoring system. The performance of this scoring system in terms of prediction and calibration was assessed using C statistics and the Hosmer‒Lemeshow test. RESULTS: Among patients in the training and test cohorts, 74 (39.6%) and 25 (31.6%), respectively, exhibited EPE after RP. The formulated scoring system incorporated the following factors: PSAD, index tumor length, bulging prostatic contour, and tumor-capsule interface > 10 mm as identified on MRI. This scoring system demonstrated strong prediction performance for EPE in both the training (C statistic, 0.87 [95% confidence interval, 0.86-0.87]) and test cohorts (C statistic, 0.85 [0.83-0.89]). Furthermore, the scoring system exhibited good calibration in both cohorts (P = 0.988 and 0.402, respectively). CONCLUSION: Our scoring system, built upon MRI features defined by the PI-RADS, offers valuable assistance in assessing the likelihood of EPE after RP.

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

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.

Tolerability of Olaparib Combined with Abiraterone in Patients with Metastatic Castration-resistant Prostate Cancer: Further Results from the Phase 3 PROpel Trial.

BACKGROUND: The PROpel study (NCT03732820) demonstrated a statistically significant progression-free survival benefit with olaparib plus abiraterone versus placebo plus abiraterone in the first-line metastatic castration-resistant prostate cancer (mCRPC) setting, irrespective of homologous recombination repair mutation status. OBJECTIVE: We report additional safety analyses from PROpel to increase clinical understanding of the adverse-event (AE) profiles of olaparib plus abiraterone versus placebo plus abiraterone. DESIGN, SETTING, AND PARTICIPANTS: A randomised (1:1), double-blind, placebo-controlled trial was conducted at 126 centres in 17 countries (October 2018-January 2020). Patients had mCRPC and no prior systemic mCRPC treatment. INTERVENTION: Olaparib (300 mg bid) or placebo with abiraterone (1000 mg od) plus prednisone/prednisolone (5 mg bid). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The data cut-off date was July 30, 2021. Safety was assessed by AE reporting (Common Terminology Criteria for Adverse Events v4.03) and analysed descriptively. RESULTS AND LIMITATIONS: The most common AEs (all grades) for olaparib plus abiraterone versus placebo plus abiraterone were anaemia (46.0% vs 16.4%), nausea (28.1% vs 12.6%), and fatigue (27.9% vs 18.9%). Grade ≥3 anaemia occurred in 15.1% versus 3.3% of patients in the olaparib plus abiraterone versus placebo plus abiraterone arm. The incidences of the most common AEs for olaparib plus abiraterone peaked early, within 2 mo, and were managed typically by dose modifications or standard medical practice. Overall, 13.8% versus 7.8% of patients discontinued treatment with olaparib plus abiraterone versus placebo plus abiraterone because of an AE; 3.8% versus 0.8% of patients discontinued because of anaemia. More venous thromboembolism events were observed in the olaparib plus abiraterone arm (any grade, 7.3%; grade ≥3, 6.8%) than in the placebo plus abiraterone arm (any grade, 3.3%; grade ≥3, 2.0%), most commonly pulmonary embolism (6.5% vs 1.8% for olaparib plus abiraterone vs placebo plus abiraterone). CONCLUSIONS: Olaparib plus abiraterone has a manageable and predictable safety profile. PATIENT SUMMARY: The PROpel trial showed that in patients who had not received any previous treatment for metastatic castration-resistant prostate cancer, olaparib combined with abiraterone was more effective in delaying progression of the disease than abiraterone alone. Most side effects caused by combining olaparib with abiraterone could be managed with supportive care methods, by pausing olaparib administration for a short period of time and/or by reducing the dose of olaparib.

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

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

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

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

Repeated Injections of Mesenchymal Stem Cell-Derived Exosomes Ameliorate Erectile Dysfunction in a Cavernous Nerve Injury Rat Model.

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.

Spatial architectures of somatic mutations in normal prostate, benign prostatic hyperplasia and coexisting prostate cancer.

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.

Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [177Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer.

OBJECTIVE: 177Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [177Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [177Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [177Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organ- and tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. RESULTS: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. CONCLUSION: [177Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

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

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

DNA methylation biomarkers distinguishing early-stage prostate cancer from benign prostatic hyperplasia.

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.

Effectiveness of a personalized digital exercise and nutrition-based rehab program for patients with gastric cancer after surgery: Study protocol for a randomized controlled trial.

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).

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

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

Impact of modified bladder neck suspension on early recovery of continence after robot-assisted radical prostatectomy (RARP).

The incontinence after RARP significantly decreases the quality of life in prostate cancer patients. A number of techniques have been introduced for the recovery of continence after RARP. Although, the mechanism of the continence recovery is still unclear. We aimed to evaluate the early recovery of continence after RARP by inducing early anterior adhesion and reducing the hypermobility of the urethra through the modified bladder neck suspension (BNS) procedure. From March 2018 to February 2020, a total of 227 consecutive patients who underwent RARP (by single surgeon) were included. Patients were divided into two groups based on operation procedure (Standard procedure vs BNS procedure). Demographics, perioperative variables, and pathologic outcome were analyzed. We assessed recovery of continence at 1, 3, 6 and 9 months after surgery. Postoperative recovery of continence defined as the use of no pad during 24 h. Multivariable logistic regression analyses were performed to evaluate independent predictors of the early recovery of continence at 1 month. We performed RARP with standard procedure (n = 106) or BNS procedure (n = 121). There was no statistical difference in perioperative variables between the two groups except anastomosis time (21.6 ± 12.9 vs 17.0 ± 7.6, p = 0.003). The pad free continence rate were 80.2% (standard group) and 91.3% (BNS group) at 9 month after RARP (p = 0.037). However, early continence rate (1mo) were significantly higher in the BNS group (12.3% vs 29.1%, p = 0.004). On multivariate logistic analyses, BNS procedure (odds ratio [OR] 2.78, 95% confidence interval [CI] 1.03-7.45, p = 0.0426), age (OR 0.92, CI 0.86-0.98, p = 0.0154) were independent factor for early recovery of continence after RARP. The modified bladder neck suspension procedure showed significantly better outcomes than the standard procedure in terms of the early recovery of urinary continence.

Erectile Dysfunction Treatment Using Stem Cell Delivery Patch in a Cavernous Nerve Injury Rat Model.

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.