A Marine Collagen-Based 3D Scaffold for In Vitro Modeling of Human Prostate Cancer Niche and Anti-Cancer Therapeutic Discovery.

Recently, the need to develop a robust three-dimensional (3D) cell culture system that serves as a valuable in vitro tumor model has been emphasized. This system should closely mimic the tumor growth behaviors observed in vivo and replicate the key elements and characteristics of human tumors for the effective discovery and development of anti-tumor therapeutics. Therefore, in this study, we developed an effective 3D in vitro model of human prostate cancer (PC) using a marine collagen-based biomimetic 3D scaffold. The model displayed distinctive molecular profiles and cellular properties compared with those of the 2D PC cell culture. This was evidenced by (1) increased cell proliferation, migration, invasion, colony formation, and chemoresistance; (2) upregulated expression of crucial multidrug-resistance- and cancer-stemness-related genes; (3) heightened expression of key molecules associated with malignant progressions, such as epithelial-mesenchymal transition transcription factors, Notch, matrix metalloproteinases, and pluripotency biomarkers; (4) robust enrichment of prostate cancer stem cells (CSCs); and (5) enhanced expression of integrins. These results suggest that our 3D in vitro PC model has the potential to serve as a research platform for studying PC and prostate CSC biology, as well as for screening novel therapies targeting PC and prostate CSCs.

Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury.

Prolonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing therapeutic interventions to revert immune suppression in immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities of thymic epithelial cells (TECs), including cell proliferation, thymocyte adhesion, and the gene expression of thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTß, IL-22R, RANK, LTßR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, and CK8 through the NF-κB signal transduction pathway. Furthermore, our study also revealed the cytoprotective effects of FCPs on TECs against cyclophosphamide-induced cellular injury through the NF-κB signaling pathway. Importantly, FCPs exhibited a significant capability to facilitate thymic regeneration in mice after cyclophosphamide-induced damage via the NF-κB pathway. Taken together, this study sheds light on the role of FCPs in TEC function, thymopoiesis, and thymic regeneration, providing greater insight into the development of novel therapeutic strategies for effective thymus repopulation for numerous clinical conditions in which immune reconstitution is required.

Fish Collagen Peptides Protect against Cisplatin-Induced Cytotoxicity and Oxidative Injury by Inhibiting MAPK Signaling Pathways in Mouse Thymic Epithelial Cells.

Thymic epithelial cells (TECs) account for the most abundant and dominant stromal component of the thymus, where T cells mature. Oxidative- or cytotoxic-stress associated injury in TECs, a significant and common problem in many clinical settings, may cause a compromised thymopoietic capacity of TECs, resulting in clinically significant immune deficiency disorders or impairment in the adaptive immune response in the body. The present study demonstrated that fish collagen peptides (FCP) increase cell viability, reduce intracellular levels of reactive oxygen species (ROS), and impede apoptosis by repressing the expression of Bax and Bad and the release of cytochrome c, and by upregulating the expression of Bcl-2 and Bcl-xL in cisplatin-treated TECs. These inhibitory effects of FCP on TEC damage occur via the suppression of ROS generation and MAPK (p38 MAPK, JNK, and ERK) activity. Taken together, our data suggest that FCP can be used as a promising protective agent against cytotoxic insults- or ROS-mediated TEC injury. Furthermore, our findings provide new insights into a therapeutic approach for the future application of FCP in the prevention and treatment of various types of oxidative- or cytotoxic stress-related cell injury in TECs as well as age-related or acute thymus involution.

Relationship between each IPSS item score and erectile dysfunction in the Korean Internet Sexuality Survey (KISS): do men with weak streams have low sexual function?

OBJECTIVES: The current results show that lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are co-prevalent conditions. The objective of this study was to determine which LUTS among seven items on the International Prostate Symptom Scores (IPSS) were related to ED in the general population. METHODS: The Korean Internet Sexuality Survey was performed in 2006 and 2016. We sent emails and surveyed the panelists registered at an Internet survey agency. The inclusion criteria were sexually active men aged between 20 and 69. Data, including the International Index of Erectile Function-5 (IIEF-5) and IPSS scores were extracted from the surveys. Logistic regression analyses were performed to determine the factors related to 'any degree of ED' (IIEF-5 < 22) or 'more than mild ED' (IIEF-5 < 17). RESULTS: The mean age of 1464 men was 39.2 ± 11.4 years. The mean total IPSS and IIEF-5 scores were 7.2 ± 6.5 and 20.8 ± 3.3 points, respectively. The IIEF-5 and total IPSS scores showed significant negative relationships (r = - 0.251, p < 0.001). Among the seven IPSS items, IPSS 5 (weak stream, r = - 0.243, p < 0.001) was most strongly correlated with the IIEF-5 scores. On multivariate analysis, IPSS 3 (intermittency, OR 0.160, 95% CI 1.010-1.333, p = 0.035) and IPSS 7 (nocturia, OR 1.238, 95% CI 1.077-1.423, p = 0.003) were significantly related to 'any degree of ED'. 'More than mild ED' was significantly related to IPSS 5 (weak stream, OR 1.267, 95% CI 1.058-1.518, p = 0.010). CONCLUSIONS: Every LUTS listed in the IPSS items was negatively correlated with erectile function. Among the seven IPSS items, IPSS 5 (weak stream) was the most related to 'more than mild ED'.

Ten-Year Interval Changes in the Prevalence of Self-Identified Premature Ejaculation and Premature Ejaculation Based on an Estimated Intravaginal Ejaculation Latency Time of <3 Minutes in the General Population: The Korean Internet Sexuality Survey (KISS) 2016.

INTRODUCTION: Because the prevalence of premature ejaculation (PE) may change with time, few studies have been conducted over a 10-year time interval. AIM: A 10-year time interval survey to determine whether there was a change in the prevalence of self-identified PE and PE defined on the basis of an estimated intravaginal ejaculation latency time of <3 minutes in adult Korean men, even after adjusting for various sociocultural factors. METHODS: We sent an e-mail to the panels registered in the same Internet survey agency in 2006, asking them to participate in a questionnaire-based survey of the same study design. 1,401 participants were enrolled in the 2016 study that included 800 subjects in their 20s-50s. The PE prevalence adjusted for age was evaluated because the proportion of participants per age was different between the 2 surveys. The age-adjusted prevalence of self-identified PE and PE with an estimated intravaginal ejaculation latency time of 3 minutes, which meets the diagnostic criteria for PE set by the International Society for Sexual Medicine (PE), was evaluated. MAIN OUTCOME MEASURES: Changes in the overall prevalence of self-identified PE and PE in over a decade were evaluated. RESULTS: The overall age-adjusted prevalence of self-identified PE increased from 19.0% in 2006 to 21.6% in 2016; however, the result was not statistically significant (P = .244). The overall age-adjusted prevalence of PE increased from 1.8-4.0% in 2006 and 2016, respectively (P = .012). The risk factors of self-identified PE were few intercourses per month, masturbation, and self-identified erectile dysfunction. In addition, the risk factors of PE were aging, high body mass index, few intercourses per month, and masturbation. CLINICAL IMPLICATION: The prevalence of PE has increased over 10 years. However, this increase may be due to sociocultural changes and should be more concerned with these factors. STRENGTH & LIMITATIONS: This study was the first to conduct a 10-year interval Web-based survey on the prevalence and risk factors of PE. However, this was not a cohort study with the same participants. CONCLUSION: The overall age-adjusted prevalence of PE increased significantly over a decade, and sociocultural factors such as lifestyle were associated with the difference of PE prevalence for 10 years. However, more research is needed to determine how these sociocultural changes affect PE prevalence. Song WH, Yoo S, Oh S, et al. Ten-Year Interval Changes in the Prevalence of Self-Identified Premature Ejaculation and Premature Ejaculation Based on an Estimated Intravaginal Ejaculation Latency Time of <3 Minutes in the General Population: The Korean Internet Sexuality Survey (KISS) 2016. J Sex Med 2019;16:512-521.

Long-Term Outcomes of Laser Prostatectomy for Storage Symptoms: Comparison of Serial 5-Year Followup Data between High Performance System Photoselective Vaporization and Holmium Laser Enucleation of the Prostate.

PURPOSE: We compared long-term storage symptom outcomes between photoselective laser vaporization of the prostate with a 120 W high performance system and holmium laser enucleation of the prostate. We also determined factors influencing postoperative improvement of storage symptoms in the long term. MATERIALS AND METHODS: Included in our study were 266 men, including 165 treated with prostate photoselective laser vaporization using a 120 W high performance system and 101 treated with holmium laser enucleation of the prostate, on whom 60-month followup data were available. Outcomes were assessed serially 6, 12, 24, 36, 48 and 60 months postoperatively using the International Prostate Symptom Score, uroflowmetry and the serum prostate specific antigen level. Postoperative improvement in storage symptoms was defined as a 50% or greater reduction in the subtotal storage symptom score at each followup visit after surgery compared to baseline. RESULTS: Improvements in frequency, urgency, nocturia, subtotal storage symptom scores and the quality of life index were maintained up to 60 months after photoselective laser vaporization or holmium laser enucleation of the prostate. There was no difference in the degree of improvement in storage symptoms or the percent of patients with postoperative improvement in storage symptoms between the 2 groups throughout the long-term followup. However, the holmium laser group showed greater improvement in voiding symptoms and quality of life than the laser vaporization group. On logistic regression analysis a higher baseline subtotal storage symptom score and a higher BOOI (Bladder Outlet Obstruction Index) were the factors influencing the improvement in storage symptoms 5 years after prostate photoselective laser vaporization or holmium laser enucleation. CONCLUSIONS: Our serial followup data suggest that storage symptom improvement was maintained throughout the long-term postoperative period for prostate photoselective laser vaporization with a 120 W high performance system and holmium laser enucleation without any difference between the 2 surgeries. Also, more severe storage symptoms at baseline and a more severe BOOI predicted improved storage symptoms in the long term after each surgery.

Design and simulation of novel laparoscopic renal denervation system: a feasibility study.

PURPOSE: In this study, we propose a novel laparoscopy-based renal denervation (RDN) system for treating patients with resistant hypertension. In this feasibility study, we investigated whether our proposed surgical instrument can ablate renal nerves from outside of the renal artery safely and effectively and can overcome the depth-related limitations of the previous catheter-based system with less damage to the arterial walls. METHOD: We designed a looped bipolar electrosurgical instrument to be used with laparoscopy-based RDN system. The tip of instrument wraps around the renal artery and delivers the radio-frequency (RF) energy. We evaluated the thermal distribution via simulation study on a numerical model designed using histological data and validated the results by the in vitro study. Finally, to show the effectiveness of this system, we compared the performance of our system with that of catheter-based RDN system through simulations. RESULTS: Simulation results were within the 95% confidence intervals of the in vitro experimental results. The validated results demonstrated that the proposed laparoscopy-based RDN system produces an effective thermal distribution for the removal of renal sympathetic nerves without damaging the arterial wall and addresses the depth limitation of catheter-based RDN system. CONCLUSIONS: We developed a novel laparoscope-based electrosurgical RDN method for hypertension treatment. The feasibility of our system was confirmed through a simulation study as well as in vitro experiments. Our proposed method could be an effective treatment for resistant hypertension as well as central nervous system diseases.

A 10-Year Interval Study About the Sexual Life and Attitudes of Korean Women: The Korean Internet Sexuality Survey (KISS) 2014, Part 2.

BACKGROUND: Many studies on sexual attitudes and behavior have been performed to improve sexual health. AIM: To evaluate changing trends in Korean female sexual life and attitudes in an internet-based survey at 10-year intervals. METHODS: The survey was targeted toward 20- to 59-year-old women who were asked to complete the questionnaire only if they were sexually active. The survey contained 110 questions about demographic statistics, sexual life, and attitudes that were crafted based on the 2004 study. OUTCOMES: Results of the 2004 study vs those of the 2014 study. RESULTS: In total, 516 women participated in the study; the questionnaire response rate was 16.0%. The mean frequency of intercourse (FOI) per month was 3.46 ± 2.56 in 2014 vs 5.34 ± 3.84 in 2004. Women in their 20s and 30s in 2014 reported a lower mean FOI than those in 2004. There was no significant difference in the mean FOI in 2004 vs 2014 for women who in their 40s. Risk factors for lower FOI were being older, being single, and having dyspareunia. Most Korean women had positive attitudes toward sex (3.2 ± 0.6 of 5) and considered it as important (3.3 ± 0.7 of 5) as those surveyed in 2004. However, women 20 to 39 years old had less positive attitudes toward sex than in the past decade. Women in their 40s were more active and had more conversations with their partners. Of women using contraceptives, 63.8% were found to use less effective methods, such as intercourse withdrawal and the fertility awareness method. CLINICAL IMPLICATIONS: Assessment of changing trends in Korean female sexual life, attitudes, and contraceptive methods could help to establish proper national sexual education programs and campaigns. STRENGTHS AND LIMITATIONS: This study was not a cohort study, because subjects in the 2014 were not identical to those in the 2004 study. Nevertheless, we applied the same inclusion and exclusion criteria for this internet survey, a suitable tool to evaluate the sex life of women, which is often considered a sensitive and private issue in Asian culture. CONCLUSIONS: Compared with the 2004 survey, young Korean women had fewer sexual relationships and had a less positive attitude toward sex. In addition, many women used less effective methods of contraception. Park J, Min B, Shin H, et al. A 10-Year Interval Study About the Sexual Life and Attitudes of Korean Women: The Korean Internet Sexuality Survey (KISS) 2014, Part 2. J Sex Med 2017;14:1142-1151.

Prostate Cancer in a Patient with a Family History of BRCA Mutation: a Case Report and Literature Review.

One of the most significant risk factors for prostate cancer (PC) is a family history of the disease, with germ-line mutations in the breast cancer predisposition gene (BRCA) 2 conferring the highest risk. We here report a 56-year-old man presented with painful gait disturbance and diagnosed PC with multiple disseminated bone metastases. The patient had a strong family history of breast cancer with his 2 nieces affected. Furthermore, his aunts and uncles from both sides were diagnosed with stomach, ovarian, and colorectal cancers. His genomic sequencing analysis of the BRCA genes revealed the same BRCA2 deleterious mutation that his breast cancer-affected nieces carried. Previous studies have suggested that BRCA2-mutated PC is associated with a more aggressive phenotype and poor prognosis. Our experience in the present case also indicated the urgent needs for novel treatment modality and PC screening in this high-risk group of patients.

The Impact of the Percent of Residual Prostate-Specific Antigen on Metastasis-Free Survival in Patients with Persistent Prostate-Specific Antigen after Radical Prostatectomy.

PURPOSE: Persistent levels of prostate-specific antigen (PSA) is a poor prognostic factor for recurrence after radical prostatectomy (RP). We investigated the impact of the percentage of residual PSA (%rPSA) [(post-/preoperative PSA)×100], representing a biochemical residual tumor, and the first postoperative PSA (fPSA) level on metastasis-free survival (MFS) in men with persistent levels of PSA after RP. MATERIALS AND METHODS: We retrospectively identified male patients within a single tertiary referral hospital database who harbored persistent (≥0.1 ng/mL) vs. undetectable (<0.1 ng/mL) PSA levels 4 to 8 weeks after RP. Kaplan-Meier analyses and Cox regression models were used to test the effect of persistent PSA levels, the fPSA level, and %rPSA on MFS. RESULTS: Of 1,205 patients, 178 patients with persistent PSA levels were enrolled. Seven-year MFS rates were 60.5% vs. 84.3% (p<0.001) for patients with a %rPSA ≥6% and <6%, respectively. Multivariable Cox regression models of the overall cohort revealed that persistent PSA levels (hazard ratio [HR], 3.94; p=0.010), extracapsular extension (HR, 4.17; 95% confidence interval [CI], 1.06-16.41; p=0.041), and pathological Gleason grade group (pGGG) (HR, 3.69; 95% CI, 1.32-10.27; p=0.013) were independent predictors of metastasis. Multivariable Cox regression models in men with persistent PSA levels revealed that the %rPSA (HR, 8.92; 95% CI, 1.74-45.71; p=0.009) and pGGG 4-5 (HR, 4.13; 95% CI, 1.22-13.96; p=0.022) were independent predictors of distant metastasis, but not the fPSA level after surgery. CONCLUSIONS: Persistent levels of PSA were associated with worse MFS after RP. In men with persistent PSA levels after RP, the %rPSA is a valuable predictor of MFS unlike the fPSA level.

Impact of Ultrasonographic Findings on Cancer Detection Rate during Magnetic Resonance Image/Ultrasonography Fusion-Targeted Prostate Biopsy.

PURPOSE: To evaluate the impact of paired transrectal ultrasonography (TRUS) findings of index lesions identified by multiparametric magnetic resonance imaging (mpMRI) on the detection rate of clinically significant prostate cancer (csPCa, Gleason score ≥7) during MRI/US fusion-targeted biopsies. MATERIALS AND METHODS: From 2019 to 2021, TRUS findings of paired index lesions were prospectively collected from MRI/US cognitive (cTB, n=299) or program-assisted (pTB, n=294) fusion-targeted biopsies. csPCa detection rates according to the presence of a paired hypoechoic lesion (HoEL) and predictive factors for csPCa detection by targeted biopsy were evaluated. RESULTS: Among 593 patients with visible lesions on upfront mpMRI (Prostate Imaging-Reporting and Data System score ≥3), 288 (48.6%) had paired HoELs on TRUS. The csPCa detection rates in targeted biopsy patients with and without paired HoELs were 56.3% and 10.5% (p<0.001), respectively. Detection rates in patients with and without paired HoELs in the peripheral zone were 65.0% and 14.5%, respectively, and in the transition zone, 37.4% and 8.2%, respectively. In the cTB cohort, a paired HoEL (OR=6.25; p<0.001) was an independent predictive factor for the detection of csPCa in the target core, but not in the pTB cohort (OR=1.92; p=0.107). CONCLUSIONS: During MRI/US fusion-targeted biopsy, csPCa detection rate was higher in patients with paired HoELs on TRUS than in those without it. After adjustment of the zonal location and mpMRI findings, the presence of paired HoELs is an independent predictive factor for csPCa detection in cTB, but not in pTB. Therefore, paired HoELs improve only the targeting of visually estimated biopsies.

Corrigendum: Correction of the Affiliation. Complementing the active surveillance criteria with multiparametric magnetic resonance imaging.

This corrects the article on p. 573 in vol. 61, PMID: 33135402.

Feasibility study of a novel rectal cooling system for hypothermic radical prostatectomy in a swine model.

Thermal damage and inflammatory responses of the sphincter and neurovascular bundles (NVBs) are responsible for post-prostatectomy incontinence and erectile dysfunction. Intraoperative hypothermia in the pelvic cavity may reduce the occurrence of these complications. We evaluated the feasibility of a novel rectal cooling system using an animal model. A novel rectal cooling system consisting of a cooling console and a multi-lumen rectal balloon was developed. We conducted animal tests on male pigs to evaluate the efficacy and safety of the system. The primary endpoint was to maintain the temperature of the NVBs at 25℃ (±5℃) during and after the electrocauterization of the bladder neck for 10 seconds. The safety endpoint was device-related complications or significant changes in the core body temperature of the pigs. The NVB temperature was below 30℃ within 3 minutes of activation of the rectal balloon. The temperature of the proximal NVB was consistently maintained below 25℃ in all cases. The temperature 1 cm from the bladder neck did not rise above 38℃ and dropped to the initial level within 1 minute after electrocauterization. During cooling, the minimum temperature at the apex of the prostate was reduced to 10.1℃. There were no device-related complications or significant changes in core body temperature throughout the experiment. Animal tests suggest the feasibility and safety of this novel rectal cooling system. A first-in-human trial to assess the safety and efficacy of this system during radical prostatectomy is warranted.

Changing Trends in Sexual Debut Age in the Korean Internet Sexuality Survey.

PURPOSE: To evaluate changing trends in relation to the sexual debut age and socioeconomic status (SES) in Korea. MATERIALS AND METHODS: The Korean Internet Sexuality Survey (KISS) was conducted for in 2004, 2006, 2014, and 2016. We sent emails and surveyed people registered at an Internet survey agency. To determine the changing trends in sexual debut age, we collected and compared the responses of females in their 20s in 2004 (n=253) and 2014 (n=131) and collected and compared the responses of males in their 20s in 2006 (n=87) and 2016 (n=200). RESULTS: In females, SES factors such as occupation, income, and academic background were not related to early sexual debut age. In the 2006 male study, early sexual debut age was associated with occupation, income, and academic background. However, in the 2016 male study, participants' academic background was the only significant factor about early sexual debut age. In both the male and female studies, early sexual debut age was related to a higher number of sexual partners in life. Also, in both female cohorts (2004 and 2014), the number of pregnancies and the incidents of sexual abuse experienced were higher in the early sexual debut groups. CONCLUSIONS: Factors influencing early sexual debut were different in time and between men and women. And there was no significant association between SES factors and early sexual debut age in women. However, early sexual debut caused multiple problems, especially in young women. Thus, we need to create some suitable strategies to address these problems.

External validation of European Association of Urology NMIBC risk scores to predict progression after transurethral resection of bladder tumor in Korean patients with non-muscle-invasive bladder cancer.

PURPOSE: This study aimed to validate the newly proposed risk model in Korean patients diagnosed with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A retrospective review was performed with 1,238 patients who underwent transurethral resection of bladder tumor from 2009 to 2020. We included 973 patients and categorized them into four risk groups according to the European Association of Urology (EAU) NMIBC risk stratification standards, which incorporate the World Health Organization 2004/2016 grading classification. Kaplan-Meyer survival analysis and multivariable analysis of time to progression were performed to calculate the probability of progression for all risk groups. RESULTS: A total of 973 patients were followed for 54.85 months. Patients were classified according to the risk factors proposed by the new NMIBC risk table and stratified into low, intermediate, high, and very high-risk groups based on the table. Cancer progression into muscle-invasive bladder cancer (MIBC) in each risk group was observed in 7 (4.4%), 24 (15.2%), 76 (48.1%), and 51 (32.3%) individuals, respectively. The progression rate was distinguishable between risk groups in the Kaplan-Meier progression-free survival analysis, and higher risk was associated with a higher rate of progression. The new NMIBC risk variables were demonstrated to have prognostic value in the multivariate analysis. The very high-risk group was associated with progression to muscle-invasive disease. CONCLUSIONS: This study demonstrates that the new EAU NMIBC risk group categorization is feasible in predicting the progression of NMIBC into MIBC in the Korean population and thus should be applied to clinical practice in Korea.

Conditional biochemical recurrence-free survival after radical prostatectomy in patients with high-risk prostate cancer.

BACKGROUND: Conditional survival is defined as the likelihood of subsequent survival given the precondition of having already survived a certain length of time. Most analyses of conditional survival in prostate cancer are not clinically applicable because they do not analyze outcomes conditioned on the durability of cure after treatment. We evaluated the conditional probability of biochemical recurrence (BCR)-free survival (C-BCRFS) after radical prostatectomy (RP) for prostate cancer according to the National Comprehensive Cancer Network risk classification and prognostic factors in patients who survived several years without BCR. METHODS: Between January 2009 and December 2018, 877 patients with complete clinicopathologic and follow-up data were included. Using the Kaplan-Meier estimation, the probabilities of C-BCRFS after RP were estimated in patients who did not experience BCR at 0-4 years. C-BCRFS was analyzed according to the National Comprehensive Cancer Network risk classification and compared using the log-rank test. Prognostic factors at each year without BCR were evaluated using multivariable Cox regression analysis. RESULTS: The median follow-up duration and patient age were 48 months and 67 years, respectively. As the BCR-free interval increased (baseline, 1, 2, 3, and 4 years after RP), the 5-year C-BCRFS rates improved marginally (74.8%, 83.2%, 89.1%, 93.6%, and 98.5%, respectively). However, the 5-year C-BCRFS rates in the high/very high-risk group rose from 54.0% at baseline to 67.6%, 80.3%, 88.6, and 97.8% after 1-4 years free of BCR, respectively. In patients with a BCR-free duration more than 1 year, only seminal vesicle invasion and pathological Gleason score were significant predictive factors of BCR thereafter. CONCLUSION: In the high/very high-risk group, the C-BCRFS markedly improved as the interval without BCR increased. In patients who were BCR-free for several years, seminal vesicle invasion and pathological Gleason score were prognostic factors of continued BCRFS. This is useful not only for patient counseling but also to optimize postoperative follow-up strategies.

Complementing the active surveillance criteria with multiparametric magnetic resonance imaging.

PURPOSE: To evaluate the usefulness of multiparametric magnetic resonance imaging (mpMRI) to avoid misclassification of patients with clinically significant prostate cancer (PCa) into active surveillance (AS). MATERIALS AND METHODS: Patients with Gleason grade group (GG) 1 PCa on systematic biopsy who underwent mpMRI before radical prostatectomy (RP) were included. mpMRI and pathologic results were compared between the AS and NOT-AS candidates. Unfavorable disease was defined as the identification of T3-4 disease or GG upgrade in the RP specimen. We established an ideal cutoff Prostate Imaging Reporting and Data System (PI-RADS) score for predicting unfavorable disease, and analyzed the location of index lesions on mpMRI. RESULTS: PI-RADS scores were not significantly different between AS candidates (n=64) and NOT-AS candidates (n=136; p=0.629). Among 64 AS candidates, GG upgrading and unfavorable disease were diagnosed after RP in 24 (37.5%) and 25 (39.1%) patients, respectively. The rate of unfavorable disease was greater for patients with a PI-RADS score of 5 (83.3%) than in those with a score ≤4 (34.5%; p=0.030). Moreover, most PI-RADS 5 lesions in AS candidates were located in the anterior half of the prostate, with GG upgrading on targeted biopsy in 75.0% of cases. CONCLUSIONS: Among the patients with GG 1 PCa, PI-RADS scores did not differ significantly between AS and NOT-AS candidates. Nonetheless, AS candidates with PI-RADS 5 lesions were diagnosed with unfavorable disease in >80% of RP specimens. Significant cancer located in the anterior half of the prostate including the transitional zone can be missed by systematic biopsy.

Quantitative analysis of renal arterial variations affecting the eligibility of catheter-based renal denervation using multi-detector computed tomography angiography.

Catheter-based renal denervation (RDN) was introduced to treat resistant hypertension. However, the reduction in blood pressure after the RDN was modest. Catheter-based RDN was performed only at main renal arteries, except for accessory and branch arteries due to the diameter being too small for the catheter to approach. Here, we retrospectively analyzed the anatomy of diverse renal arteries via 64-channel multi-detector computed tomography angiograms of 314 consecutive donors who underwent living donor nephrectomy from January 2012 to July 2017. Occurrence rates of one or more accessory renal arteries in donors were 25.3% and 19.4% on the left and right sides, respectively. Early branching rates before 25 mm from the aorta to the right and left renal arteries were 13.7% and 10.5%, respectively. Overall, 63.1% and 78.3% of donors had no accessory artery bilaterally and no branched renal artery, respectively. As a result, 47.1% had only main renal arteries without an accessory artery and early-branching artery. Approximately half of the donors had multiple small renal arteries bilaterally, for which catheter-based denervation may not be suitable. Thus, preoperative computed tomography angiography requires careful attention to patient selection, and there is a need for improved methods for denervation at various renal arteries.

Animal model evaluation of a novel renal denervation system for future laparoscopic treatment of resistant hypertension.

Purpose: Although percutaneous catheter-based ablation of renal sympathetic nerve fibers has been used in the treatment of patients with resistant hypertension, a recent phase III study did not confirm its efficacy. In this study, we developed a novel laparoscopic renal denervation system and evaluated its safety and initial feasibility using an animal model. Materials and Methods: A novel surgical instrument that uses a smart algorithm with temperature-monitoring feedback was developed. We used 4 male pigs (6 weeks old, weighing approximately 45 kg each) to evaluate the safety and efficacy of the laparoscopic renal denervation system. We performed immunohistochemical staining analysis after renal denervation using various tip temperatures and over various durations through an open approach. Results: When the temperature of the outer wall of the renal artery was maintained at 90℃ for 180 seconds, the artery was completely denervated without damaging its inner layer, as evaluated using Masson's trichrome staining. When the temperature ranged from 70℃ to 90℃ and the duration ranged from 90 to 420 seconds, partial or complete denervation without significant vessel injury was confirmed with anti- growth-associated protein 43 and anti-S100 staining. Conclusions: This animal study confirmed the safety and feasibility of the novel laparoscopic renal denervation system. A safe and effective protocol was developed with ablation at a constant tissue temperature of 70℃ to 90℃ within 180 seconds. However, further developments are necessary before its clinical use.

Laparoscopic Renal Denervation System for Treating Resistant Hypertension: Overcoming Limitations of Catheter-Based Approaches.

GOAL: In a pivotal clinical trial, the percutaneous catheter-based renal denervation system developed to treat resistant hypertension did not show effectiveness in reducing blood pressure because of its fundamental limitation to ablate deeper nerves present around the renal artery. METHODS: We propose a new renal denervation strategy called laparoscopicdenervation system (LDS) based-on laparoscopy procedure to ablate the renal nerves completely but inhibit the thermal arterial damage.The system has flexible electrodes to bend around the arterial wall to ablate nervesThe simulation study using validated in-silico models evaluated the heat distributionon the outer arterial wall,and an acute animal study (swine model) was conducted to demonstrate the feasibility of LDS in vivo. RESULTS: The simulation studyconfirmedthat LDS could localize the heat distributionbetween the electrode and the outer arterial wall. In the animal study, we could maximize nerve denervation by the localizing ablation energy within the renal nerves and achieve nerve denaturationand decrease in neural density by 20.78% (P < 0.001), while maintaining a constant tip temperature of 65 °C for the duration of 70 s treatment. The study confirmed intact lumen artery through histological analysis and acute reduction in systolic blood pressure by 9.55 mmHg (p < 0.001) Conclusion: The LDS presented here has potential to effectively and safely ablate the renal nerves, independent of anatomical variation and nerve distribution, to control hypertension in real clinical conditions. SIGNIFICANCE: LDS approach is innovative, inventive, and presents a novel technique totreat hypertension.