Purpose: This study evaluates the viability of a new method that employs transperineal targeted biopsy with frozen section analysis immediately followed by robot-assisted radical prostatectomy (RARP), bypassing the traditional systematic biopsy deemed essential by current guidelines. Materials and Methods: Patient selection was based on the following inclusion criteria: those who underwent magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy with frozen section analysis and concurrent RARP. Eligibility also required features indicative of Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesion on multiparametric MRI, along with one of these additional criteria: (1) MRI evidence suggesting extracapsular extension (ECE) with a prostate-specific antigen (PSA) level >10 ng/mL, or (2) a PSA level > 20 ng/mL. Results: Twelve patients were enrolled in this study according to inclusion criteria. The median age (interquartile range) was 73.5 (69.5–75.3) years and PSA was 22.9 (17.0–29.9) ng/mL. Three patients had PI-RADS 5 lesions, and 9 had PI-RADS 5 lesions with findings of ECE. In all cases, the diagnosis based on frozen sections confirmed adenocarcinoma. Following confirmation, each patient underwent immediate RARP. According to the final pathology report, 2 patients had International Society of Urological Pathology (ISUP) grade 2 disease, 7 patients had ISUP grade 3, 1 had ISUP grade 4, and 2 had ISUP grade 5 disease. Four patients had stage pT2 disease, 3 had stage pT3a, and 5 had stage pT3b. The median immediate reporting time of the target biopsy frozen section was 20 (19.3–24.5) minutes. No perioperative complications related to target biopsy were observed. Conclusion For patients with a strong suspicion of prostate cancer and a PI-RADS 5 lesion, integrating simultaneous prostate frozen target biopsy with radical prostatectomy may offer a feasible treatment alternative, obviating the necessity for a preoperative systematic biopsy.

Purpose: This study evaluates the viability of a new method that employs transperineal targeted biopsy with frozen section analysis immediately followed by robot-assisted radical prostatectomy (RARP), bypassing the traditional systematic biopsy deemed essential by current guidelines. Materials and Methods: Patient selection was based on the following inclusion criteria: those who underwent magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy with frozen section analysis and concurrent RARP. Eligibility also required features indicative of Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesion on multiparametric MRI, along with one of these additional criteria: (1) MRI evidence suggesting extracapsular extension (ECE) with a prostate-specific antigen (PSA) level >10 ng/mL, or (2) a PSA level > 20 ng/mL. Results: Twelve patients were enrolled in this study according to inclusion criteria. The median age (interquartile range) was 73.5 (69.5–75.3) years and PSA was 22.9 (17.0–29.9) ng/mL. Three patients had PI-RADS 5 lesions, and 9 had PI-RADS 5 lesions with findings of ECE. In all cases, the diagnosis based on frozen sections confirmed adenocarcinoma. Following confirmation, each patient underwent immediate RARP. According to the final pathology report, 2 patients had International Society of Urological Pathology (ISUP) grade 2 disease, 7 patients had ISUP grade 3, 1 had ISUP grade 4, and 2 had ISUP grade 5 disease. Four patients had stage pT2 disease, 3 had stage pT3a, and 5 had stage pT3b. The median immediate reporting time of the target biopsy frozen section was 20 (19.3–24.5) minutes. No perioperative complications related to target biopsy were observed. Conclusion For patients with a strong suspicion of prostate cancer and a PI-RADS 5 lesion, integrating simultaneous prostate frozen target biopsy with radical prostatectomy may offer a feasible treatment alternative, obviating the necessity for a preoperative systematic biopsy.

Purpose: This study evaluates the viability of a new method that employs transperineal targeted biopsy with frozen section analysis immediately followed by robot-assisted radical prostatectomy (RARP), bypassing the traditional systematic biopsy deemed essential by current guidelines. Materials and Methods: Patient selection was based on the following inclusion criteria: those who underwent magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy with frozen section analysis and concurrent RARP. Eligibility also required features indicative of Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesion on multiparametric MRI, along with one of these additional criteria: (1) MRI evidence suggesting extracapsular extension (ECE) with a prostate-specific antigen (PSA) level >10 ng/mL, or (2) a PSA level > 20 ng/mL. Results: Twelve patients were enrolled in this study according to inclusion criteria. The median age (interquartile range) was 73.5 (69.5–75.3) years and PSA was 22.9 (17.0–29.9) ng/mL. Three patients had PI-RADS 5 lesions, and 9 had PI-RADS 5 lesions with findings of ECE. In all cases, the diagnosis based on frozen sections confirmed adenocarcinoma. Following confirmation, each patient underwent immediate RARP. According to the final pathology report, 2 patients had International Society of Urological Pathology (ISUP) grade 2 disease, 7 patients had ISUP grade 3, 1 had ISUP grade 4, and 2 had ISUP grade 5 disease. Four patients had stage pT2 disease, 3 had stage pT3a, and 5 had stage pT3b. The median immediate reporting time of the target biopsy frozen section was 20 (19.3–24.5) minutes. No perioperative complications related to target biopsy were observed. Conclusion For patients with a strong suspicion of prostate cancer and a PI-RADS 5 lesion, integrating simultaneous prostate frozen target biopsy with radical prostatectomy may offer a feasible treatment alternative, obviating the necessity for a preoperative systematic biopsy.

Purpose: Erectile dysfunction (ED) is considered a microvascular disorder and serves as an indicator for the potential development of cardiovascular disease (CVD). Although left ventricular diastolic dysfunction (LVDD) reflects early myocardial damage caused by microvascular disorders, the association between ED and LVDD remains poorly elucidated. Materials and Methods: A cross-sectional study was conducted on 123 patients with ED. They underwent RigiScan, and conventional echocardiography, and attempted International Index of Erectile Function (IIEF) questionnaire. ED severity was evaluated by measuring changes in the penile base circumference and duration of penile rigidity (≥70%) during erection. The early diastolic velocity of mitral inflow (E) and early diastolic velocity of the mitral annulus (e′) were measured using echocardiography. The patients were grouped based on the presence of CVD. Results: Among 123 patients, 29 had CVD and 94 did not. Patients with CVD exhibited more pronounced ED and more severe LVDD. Associations between increased penile circumference with echocardiographic parameters were more prominent in patients with CVD than in those without CVD (ΔTtop and e′ wave, r=0.508 and r=0.282, respectively, p for interaction=0.033; ΔTbase and E/e′ ratio, r=-0.338 and r=-0.293, respectively, p for interaction <0.001). In the multivariate linear regression, the increase of penile base circumference was an independent risk factor for LVDD (e′, B=0.503; E/e′ ratio, B=-1.416, respectively, p<0.001). Conclusions ED severity correlated well with LV diastolic dysfunction, particularly in the presence of CVD. This study highlighted the potential role of ED assessment as early indicator of CVD development.

Purpose: This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. Materials and Methods: The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. Results: The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. Conclusion Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

Purpose: Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM patient-derived cells. Materials and Methods: The invasiveness of GBM TSs and ventricle spheres (VSs) were quantified via collagen-based 3D invasion assays. Gene expression profiles were obtained from microarray data. A mouse orthotopic xenograft model was used for in vivo experiments. Results: After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investigated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accelerated the invasiveness of GBM TSs and VSs, compared to the control and even tMSLC-CM. Transcriptome analyses revealed that vMSLC secreted significantly higher levels of several invasiveness-associated cytokines. Moreover, differentially expressed genes between vMSLCs and tMSLCs were enriched for migration, adhesion, and chemotaxis-related gene sets, providing a mechanistic basis for vMSLC-induced invasion of GBM TSs. In vivo experiments using a mouse orthotopic xenograft model confirmed vMSLCinduced increases in the invasiveness of GBM TSs. Conclusion Although vMSLCs are non-tumorigenic, this study adds to our understanding of how GBM cells acquire infiltrative features by vMSLCs, which are present in the region where GBM genesis originates.

BACKGROUND: For stem cell applications in regenerative medicine, it is very important to produce high-quality stem cells in large quantities in a short time period. Recently, many studies have shown big potential of graphene oxide as a biocompatible substance to enhance cell growth. We investigated if graphene oxide-coated culture plate can promote production efficiency of stem cells. METHODS: Three types of graphene oxide were used for this study. They are highly concentrated graphene oxide solution, single-layer graphene oxide solution, and ultra-highly concentrated single-layer graphene oxide solution with different single-layer ratios, and coated on cell culture plates using a spray coating method. Physiochemical and biological properties of graphene oxide-coated surface were analyzed by atomic force microscope (AFM), scanning electron microscope (SEM), cell counting kit, a live/dead assay kit, and confocal imaging. RESULTS: Graphene oxide was evenly coated on cell culture plates with a roughness of 6.4 * 38.2 nm, as measured by SEM and AFM. Young’s Modulus value was up to 115.1 GPa, confirming that graphene oxide was strongly glued to the surface. The ex vivo stem cell expansion efficiency was enhanced as bone marrow-derived stem cell doubling time on the graphene oxide decreased compared to the control (no graphene oxide coating), from 64 to 58 h, and the growth rate increased up to 145%. We also observed faster attachment and higher affinity of stem cells to the graphene oxide compared to control by confocal microscope. CONCLUSION This study demonstrated that graphene oxide dramatically enhanced the ex vivo expansion efficiency of stem cells. Spray coating enabled an ultra-thin coating of graphene oxide on cell culture plates. The results supported that utilization of graphene oxide on culture plates can be a promising mean for mass production of stem cells for commercial applications.

Purpose: This study aimed to develop and validate a predictive model for the assessment of clinically significant prostate cancer (csPCa) in men, prior to prostate biopsies, based on bi-parametric magnetic resonance imaging (bpMRI) and clinical parameters. Materials and Methods: We retrospectively analyzed 300 men with clinical suspicion of prostate cancer (prostate-specific antigen [PSA] ≥ 4.0 ng/mL and/or abnormal findings in a digital rectal examination), who underwent bpMRI-ultrasound fusion transperineal targeted and systematic biopsies in the same session, at a Korean university hospital. Predictive models, based on Prostate Imaging Reporting and Data Systems scores of bpMRI and clinical parameters, were developed to detect csPCa (intermediate/high grade [Gleason score ≥ 3+4]) and compared by analyzing the areas under the curves and decision curves. Results: A predictive model defined by the combination of bpMRI and clinical parameters (age, PSA density) showed high discriminatory power (area under the curve, 0.861) and resulted in a significant net benefit on decision curve analysis. Applying a probability threshold of 7.5%, 21.6% of men could avoid unnecessary prostate biopsy, while only 1.0% of significant prostate cancers were missed. Conclusion This predictive model provided a reliable and measurable means of risk stratification of csPCa, with high discriminatory power and great net benefit. It could be a useful tool for clinical decision-making prior to prostate biopsies.

Purpose: A critical indicator of the overall survival of patients with high-grade glioma is the successful isolation of tumor mesenchymal stem-like cells (tMSLCs), which play important roles in glioma progression. However, attempts to isolate tMSLCs from surgical specimens have not always been successful, and the reasons for this remain unclear. Considering that the amount of surgical high-grade glioma specimens varies, we hypothesized that larger surgical specimens would be better for tMSLC isolation. Materials and Methods: We assessed 51 fresh, high-grade glioma specimens and divided them into two groups according to the success or failure of tMSLC isolation. The success of tMSLC isolation was confirmed by plastic adherence, presenting antigens, tri-lineage differentiation, and non-tumorigenicity. Differences in characteristics between the two groups were tested using independent two sample t-tests, chi-square tests, or Kaplan-Meier survival analysis. Results: The mean specimen weights of the groups differed from each other (tMSLC-negative group: 469.9±341.9 mg, tMSLC positive group: 546.7±618.9 mg), but the difference was not statistically significant. The optimal cut-off value of specimen weight was 180 mg, and the area under the curve value was 0.599. Conclusion Our results suggested a minimum criterion for specimen collection, and found that the specimen amount was not deeply related to tMSLC detection. Collectively, our findings imply that the ability to isolate tMSLCs is determined by factors other than the specimen amount.

BACKGROUND: For stem cell applications in regenerative medicine, it is very important to produce high-quality stem cells in large quantities in a short time period. Recently, many studies have shown big potential of graphene oxide as a biocompatible substance to enhance cell growth. We investigated if graphene oxide-coated culture plate can promote production efficiency of stem cells. METHODS: Three types of graphene oxide were used for this study. They are highly concentrated graphene oxide solution, single-layer graphene oxide solution, and ultra-highly concentrated single-layer graphene oxide solution with different single-layer ratios, and coated on cell culture plates using a spray coating method. Physiochemical and biological properties of graphene oxide-coated surface were analyzed by atomic force microscope (AFM), scanning electron microscope (SEM), cell counting kit, a live/dead assay kit, and confocal imaging. RESULTS: Graphene oxide was evenly coated on cell culture plates with a roughness of 6.4 * 38.2 nm, as measured by SEM and AFM. Young’s Modulus value was up to 115.1 GPa, confirming that graphene oxide was strongly glued to the surface. The ex vivo stem cell expansion efficiency was enhanced as bone marrow-derived stem cell doubling time on the graphene oxide decreased compared to the control (no graphene oxide coating), from 64 to 58 h, and the growth rate increased up to 145%. We also observed faster attachment and higher affinity of stem cells to the graphene oxide compared to control by confocal microscope. CONCLUSION This study demonstrated that graphene oxide dramatically enhanced the ex vivo expansion efficiency of stem cells. Spray coating enabled an ultra-thin coating of graphene oxide on cell culture plates. The results supported that utilization of graphene oxide on culture plates can be a promising mean for mass production of stem cells for commercial applications.