Impact of Circulating Tumor Cell-Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen Transcripts in Different Stages of Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. EXPERIMENTAL DESIGN: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. RESULTS: CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. CONCLUSIONS: PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.

2023 Korean sexually transmitted infections guidelines for non-gonococcal bacterial infection (chlamydia, syphilis, etc.) by the Korean Association of Urogenital Tract Infection and Inflammation.

Non-gonococcal sexually transmitted infections (STIs) include chlamydia, syphilis, and chancroids. Chlamydia is the most common STI caused by Chlamydia trachomatis and is mainly transmitted through sexual intercourse or vertical transmission at birth. Although symptoms are mostly absent or mild, untreated chlamydial infections in females can lead to pelvic inflammatory disease, chronic pelvic pain, and infertility due to the narrowing of fallopian tubes. Syphilis is caused by Treponema pallidum and is divided into phase I, phase II, latent syphilis, and phase III. The incidence of syphilis, including congenital syphilis, has significantly increased in the United States in recent years. The chronic status of this disease can significantly increase morbidity and potentially affect almost all body organs, which, in rare cases, can lead to death. Additionally, untreated maternal syphilis can lead to fetal death and fatal congenital infections in newborns. Chancroid is an STI caused by Haemophilus ducreyi, and its prevalence is gradually decreasing in Korea and worldwide. The symptoms include shallow genital ulcers with suppurative granulomatous inflammation and tender inguinal lymphadenopathy. Chancroids can be differentiated from syphilitic chancres based on their appearance. In contrast to painless chancres, chancroids are painful. Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis are considered symbiotic bacteria. Infections caused by these bacteria are usually not considered STIs and do not require treatment unless they are suspected of being associated with infertility. This article presents the 2023 Korean STI guidelines for non-gonococcal bacterial infections.

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study.

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) occurs due to the accumulation of fat in the liver, leading to fatal liver diseases such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Elucidation of the molecular mechanisms underlying NAFLD is critical for its prevention and therapy. Here, we observed that deubiquitinase USP15 expression was upregulated in the livers of mice fed a high-fat diet (HFD) and liver biopsies of patients with NAFLD or NASH. USP15 interacts with lipid-accumulating proteins such as FABPs and perilipins to reduce ubiquitination and increase their protein stability. Furthermore, the severity of NAFLD induced by an HFD and NASH induced by a fructose/palmitate/cholesterol/trans-fat (FPC) diet was significantly ameliorated in hepatocyte-specific USP15 knockout mice. Thus, our findings reveal an unrecognized function of USP15 in the lipid accumulation of livers, which exacerbates NAFLD to NASH by overriding nutrients and inducing inflammation. Therefore, targeting USP15 can be used in the prevention and treatment of NAFLD and NASH.

Fermented Sprouts of Codonopsis lanceolata Suppress LPS-Induced Inflammatory Responses by Inhibiting NF-κB Signaling Pathway in RAW 264.7 Macrophages and CD1 Mice.

The interest in bioconversion through fermentation of sprouts produced in smart farms is increasing due to their potential health benefits. Codonopsis lanceolata (CL) is reported to alleviate inflammatory conditions, but much research is still needed to determine which types and parts of CL are most effective. This study investigated the anti-inflammatory effects of a fermented extract of CL sprouts' aerial part (F-CSA) against LPS-stimulated RAW 264.7 macrophages and mice. In the screening test, F-CSA showed the most substantial anti-inflammatory effect among several samples, containing the highest total flavonoids, tannins, and polyphenols. UPLC-ESI-Q/TOF-MS and HPLC analysis revealed that F-CSA had the highest amount of luteolin among all the CL samples analyzed. F-CSA reduced the release of inflammatory cytokines and mediators such as NO and PGE2 by inhibiting the expression levels of iNOS and COX-2 in LPS-stimulated macrophages. Further, we found that the anti-inflammatory effects of F-CSA were mediated by inhibiting the JNK/NF-κB signaling pathway. Moreover, F-CSA improved survival rates and reduced plasma levels of NO and IL-6 in CD1 mice stimulated with LPS. These findings suggest that F-CSA, which contains luteolin, can alleviate inflammation in LPS-induced RAW 264.7 cells and a CD1 mouse model by inhibiting the JNK/NF-κB signaling pathways.

Prognostic value of the endothelial activation and stress index in patients with upper tract urothelial cancer undergoing radical nephroureterectomy.

PURPOSE: The relationship with endothelial activation and stress index (EASIX), which represents the degree of endothelial dysfunction, is unwell known in upper tract urothelial carcinoma (UTUC). The present study aims to assess the prognostic value of the EASIX for recurrence-free survival (RFS) and overall survival (OS) in patients with UTUC who underwent radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 627 patients with UTUC who underwent RNU without neoadjuvant chemotherapy at three hospitals between 2002 and 2019. EASIX scores were calculated using the formula "serum lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (109/L)" and evaluated based on log2-transformed values. We divided the patients according to the EASIX score (>1.27 vs. ≤1.27). RESULTS: Among 627 patients, 380 were finally analyzed. Using maximally selected log-rank statistics, the optimal EASIX cutoff value was 1.27 on the log2 scale. The baseline characteristics were similar between the two groups except for age. The high EASIX score group had worse RFS and OS than the low EASIX score group (log-rank p=0.001 and p=0.006, respectively). At 5 years, the mean RFS and OS difference between the low and high EASIX score groups was 11.1 and 7.35 months, respectively. High EASIX score remained a key prognosticator of RFS and OS after RNU in multivariable analysis. CONCLUSIONS: EASIX score may represent endothelial dysfunction in patients with UTUC and may serve as a readily available prognostic factor for oncologic outcomes.

Coexpression of lymphocyte-activation gene 3 and programmed death ligand-1 in tumor infiltrating immune cells predicts worse outcome in renal cell carcinoma.

OBJECTIVES: Lymphocyte-activation gene 3 (LAG-3) represents a potential immune checkpoint target for cancer treatment. We investigated LAG-3 expression and its prognostic value in patients with surgically treated clear cell renal cell carcinoma (RCC) and correlated LAG-3 expression with programmed cell death ligand 1(PD-L1). METHODS: We evaluated LAG-3 and PD-L1 expression using immunohistochemistry on tissue microarrays incorporating 134 primary excision specimens of clear cell RCC (ccRCC). The patients were analyzed as two groups: the whole cohort and those with metastatic RCC (mRCC). The cancer genome atlas (TCGA) data analysis of LAG-3 was done through UALCAN web servers. RESULTS: Using the UALCAN cancer transcriptional data analysis, we found that LAG-3 was overexpressed in ccRCC. LAG-3 expression was significantly correlated with PD-L1 expression in the whole cohort and in the mRCC group (all, p < 0.05). Both LAG-3⁺ RCC and PD-L1⁺ RCC presented with a higher TNM stage and higher Fuhrman nuclear grade (all, p < 0.05). PD-L1⁺/LAG-3⁺ RCC and PD-L1⁻/LAG-3⁺ RCC showed poorer cancer-specific survival (CSS) than PD-L1⁻/LAG-3⁻ RCC (all, p = 0.01). Similarly, PD-L1⁺/LAG-3⁺ mRCC and PD-L1⁻/LAG-3⁺ mRCC showed poorer CSS than PD-L1⁻/LAG-3⁻ mRCC (all, p < 0.05). Multivariate analysis showed that PD-L1⁺/LAG-3⁺ mRCC (hazard ratio: 3.19; 95% CI: 0.77-13.67; p = 0.033) was a predictor of poor CSS. CONCLUSION: Both LAG-3⁺ and PD-L1⁺ RCC have adverse pathological features, and their coexpression predicts worse clinical outcomes. Our findings suggest LAG-3 blockade in combination with programmed cell death 1/PD-L1 blockade as a potential therapeutic approach for RCC.

A Novel Approach on Deep Learning-Based Decision Support System Applying Multiple Output LSTM-Autoencoder: Focusing on Identifying Variations by PHSMs' Effect over COVID-19 Pandemic.

Following the outbreak of the COVID-19 pandemic, the continued emergence of major variant viruses has caused enormous damage worldwide by generating social and economic ripple effects, and the importance of PHSMs (Public Health and Social Measures) is being highlighted to cope with this severe situation. Accordingly, there has also been an increase in research related to a decision support system based on simulation approaches used as a basis for PHSMs. However, previous studies showed limitations impeding utilization as a decision support system for policy establishment and implementation, such as the failure to reflect changes in the effectiveness of PHSMs and the restriction to short-term forecasts. Therefore, this study proposes an LSTM-Autoencoder-based decision support system for establishing and implementing PHSMs. To overcome the limitations of existing studies, the proposed decision support system used a methodology for predicting the number of daily confirmed cases over multiple periods based on multiple output strategies and a methodology for rapidly identifying varies in policy effects based on anomaly detection. It was confirmed that the proposed decision support system demonstrated excellent performance compared to models used for time series analysis such as statistical models and deep learning models. In addition, we endeavored to increase the usability of the proposed decision support system by suggesting a transfer learning-based methodology that can efficiently reflect variations in policy effects. Finally, the decision support system proposed in this study provides a methodology that provides multi-period forecasts, identifying variations in policy effects, and efficiently reflects the effects of variation policies. It was intended to provide reasonable and realistic information for the establishment and implementation of PHSMs and, through this, to yield information expected to be highly useful, which had not been provided in the decision support systems presented in previous studies.

Implementation of a Collaborated Antimicrobial Stewardship Program and Outpatient Parenteral Antimicrobial Therapy (OPAT) Unit-driven Monoclonal Antibody Therapy Program for COVID-19 at an NYC Hospital.

OBJECTIVES: This study aimed to assess the processes and clinical outcomes of a joint collaboration between Antimicrobial Stewardship Program (ASP) and the outpatient parenteral antimicrobial therapy (OPAT) unit for delivery of monoclonal antibody therapy for mild-to-moderate COVID-19. METHODS: We carried out a retrospective, interim analysis of our COVID-19 monoclonal antibody therapy program. Outcomes included clinical response, incidence of hospitalization, and adverse events. RESULTS: A total of 175 patients (casirivimab-imdevimab, n = 130; bamlanivimab, n = 45) were treated between December 2020 and March 1, 2021. The median time from symptom onset was 6 (IQR 4, 8) days at time of treatment. Of 135 patients available for follow-up, 71.9% and 85.9% of patients reported symptom improvement within 3 and 7 days of treatment, respectively. A total of 9 (6.7%) patients required COVID-19-related hospitalization for progression of symptoms, all within 14 days of treatment. A total of 7 (4%) patients experienced an infusion-related reaction. CONCLUSIONS: ASP-OPAT collaboration is a novel approach to implement an efficient and safe monoclonal antibody therapy program for the treatment of mild-to-moderate COVID-19.

Comparative Analysis of Proteomes and Phosphoproteomes in Patients with Prostate Cancer Using Different Surgical Conditions.

PURPOSE: To establish the standard of procedure in preparing benign and cancerous prostate tissues and evaluate the quality of proteomics and phosphoproteomics during transurethral resection of the prostate (TUR-P) with different surgical conditions. MATERIALS AND METHODS: TUR-P tissue samples from three patients, two diagnosed with prostate cancer and one with benign prostatic hyperplasia, were each analyzed under three different conditions, based on differences in energy values, tissue locations, and surgical techniques. Global- and phosphorylated proteomic profiles of prostate tissues were analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: A total of 6,019 global proteins and 4,280 phosphorylated peptides were identified in the nine tissues. The quantitative distributions of proteins and phosphorylation in tissues from the same patient were not affected by changes in the surgical conditions, but indirect relative comparisons differed among patients. Phosphorylation levels, especially of proteins involved in the androgen receptor pathway, important in prostate cancer, were preserved in each patient. CONCLUSIONS: Proteomic profiles of prostate tissue collected by TUR-P were not significantly affected by energy levels, tissue location, or surgical technique. In addition, since protein denaturation of samples through TUR-P is rarely confirmed in this study, we think that it will be an important guide for tissue samples in castration resistant prostate cancer patients, where it is difficult to obtain tissue. This result is the first report about proteomic and phosphoproteomic results with TUR-P samples in prostate cancer and will be theoretical basis in protein analysis research with prostate cancer tissues.

Hemicellulose-based hydrogels for advanced applications.

Hemicellulose-based hydrogels are three-dimensional networked hydrophilic polymer with high water retention, good biocompatibility, and mechanical properties, which have attracted much attention in the field of soft materials. Herein, recent advances and developments in hemicellulose-based hydrogels were reviewed. The preparation method, formation mechanism and properties of hemicellulose-based hydrogels were introduced from the aspects of chemical cross-linking and physical cross-linking. The differences of different initiation systems such as light, enzymes, microwave radiation, and glow discharge electrolytic plasma were summarized. The advanced applications and developments of hemicellulose-based hydrogels in the fields of controlled drug release, wound dressings, high-efficiency adsorption, and sensors were summarized. Finally, the challenges faced in the field of hemicellulose-based hydrogels were summarized and prospected.

Gut microbial shifts by synbiotic combination of Pediococcus acidilactici and lactulose in weaned piglets challenged with Shiga toxin-producing Escherichia coli.

Development of alternatives to in-feed antibiotics in the swine industry have been the focused of many pig gut microbiota studies to improve animal health. In this study, we evaluated the effects of probiotic Pediococcus acidilactici (PRO), prebiotic lactulose (PRE), and their synbiotic combination (SYN) on gut microbiota using 16S rRNA gene sequencing in weaned piglets challenged with Shiga-toxin producing Escherichia coli (STEC). Our data showed that prebiotics, probiotics and synbiotics improved the intestinal health in weaned piglets. No significant differences were observed in species richness and species diversity in weaned piglets fed prebiotics, probiotics and their synbiotic combination. However, beta diversity analysis revealed distinct clustering of the microbiota of according to dietary treatment and by oral challenge of STEC. At the phylum level, Firmicutes to Bacteroidetes ratio was lower in the dietary treatment groups than the control group. Oral supplementation of prebiotics, probiotics and synbiotics enriched the abundance of Prevotella and Roseburia. Succinivibrio was elevated in PRO group; however, Phascolarctobacterium was depleted with STEC challenge regardless of dietary treatment. Overall, our data showed that administration of synbiotics in piglets improved intestinal health through gut microbiota modulation. Our data indicated that prebiotics, probiotics and their synbiotic combination could promote intestinal health through gut microbiota modulation in weaned piglets.

Visible and infrared dual-band imaging via Ge/MoS2 van der Waals heterostructure.

Multispectral photodetectors are emerging devices capable of detecting photons in multiple wavelength ranges, such as visible (VIS), near infrared (NIR), etc. Image data acquired with these photodetectors can be used for effective object identification and navigations owing to additional information beyond human vision, including thermal image and night vision. However, these capabilities are hindered by the structural complexity arising from the integration of multiple heterojunctions and selective absorbers. In this paper, we demonstrate a Ge/MoS2 van der Waals heterojunction photodetector for VIS- and IR-selective detection capability under near-photovoltaic and photoconductive modes. The simplified single-polarity bias operation using single pixel could considerably reduce structural complexity and minimize peripheral circuitry for multispectral selective detection. The proposed multispectral photodetector provides a potential pathway for the integration of VIS/NIR vision for application in self-driving, surveillance, computer vision, and biomedical imaging.

Low Subthreshold Slope AlGaN/GaN MOS-HEMT with Spike-Annealed HfO2 Gate Dielectric.

AlGaN/GaN metal-oxide semiconductor high electron mobility transistors (MOS-HEMTs) with undoped ferroelectric HfO2 have been investigated. Annealing is often a critical step for improving the quality of as-deposited amorphous gate oxides. Thermal treatment of HfO2 gate dielectric, however, is known to degrade the oxide/nitride interface due to the formation of Ga-containing oxide. In this work, the undoped HfO2 gate dielectric was spike-annealed at 600 °C after the film was deposited by atomic layer deposition to improve the ferroelectricity without degrading the interface. As a result, the subthreshold slope of AlGaN/GaN MOS-HEMTs close to 60 mV/dec and on/off ratio>109 were achieved. These results suggest optimizing the HfO2/nitride interface can be a critical step towards a low-loss high-power switching device.

Deep Dichromatic Model Estimation Under AC Light Sources.

The dichromatic reflection model has been popularly exploited for computer vison tasks, such as color constancy and highlight removal. However, dichromatic model estimation is an severely ill-posed problem. Thus, several assumptions have been commonly made to estimate the dichromatic model, such as white-light (highlight removal) and the existence of highlight regions (color constancy). In this paper, we propose a spatio-temporal deep network to estimate the dichromatic parameters under AC light sources. The minute illumination variations can be captured with high-speed camera. The proposed network is composed of two sub-network branches. From high-speed video frames, each branch generates chromaticity and coefficient matrices, which correspond to the dichromatic image model. These two separate branches are jointly learned by spatio-temporal regularization. As far as we know, this is the first work that aims to estimate all dichromatic parameters in computer vision. To validate the model estimation accuracy, it is applied to color constancy and highlight removal. Both experimental results show that the dichromatic model can be estimated accurately via the proposed deep network.

Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint molecule expressed in hematopoietic cells, granulocytes, macrophages, and monocytes. However, few studies to date have investigated VISTA expression, especially its clinical utility, in bladder cancer. The present retrospective study aimed to examine VISTA, programmed death ligand-1 (PD-L1), and CD45 expression by immunohistochemical and immunofluorescence staining of archived pathological tissue samples from 159 patients with primary bladder cancer. The correlation between VISTA expression in immune cells (ICs) and clinicopathologic variables including PD-L1 expression in ICs was examined. Briefly, the rates of VISTA-positive ICs and VISTA-positive tumor cells were 67.9% (108/159) and 30.8% (49/159), respectively. The VISTA expression in ICs of patients with bladder cancer, including those with non-muscle-invasive bladder cancer (NMIBC), was positively correlated with tumor stage, grade, size, and multiplicity. The VISTA expression in ICs was stronger in bladder cancer cases with PD-L1-positive ICs than in those with PD-L1-negative ICs (p < 0.001). The mean intravesical recurrence-free survival was shorter in NMIBC cases with VISTA-positive ICs than in those with VISTA-negative ICs (34.0 vs 39.9 months, p = 0.03, log-rank test). In this first study to investigate VISTA expression in bladder cancer, these results implicate VISTA as a potential immunotherapeutic target and immunologic biomarker in bladder cancer.

Prognostic Impact of Resection Margin Length in Patients Undergoing Resection for Mid-Common Bile Duct Cancer: A Single-Center Experience.

INTRODUCTION: The purpose of this study was to analyze survival outcomes after segmental bile duct resection (BDR) for mid-common bile duct cancer according to the length of the tumor-free BDR margins. METHOD: A total of 133 consecutive patients underwent BDR for mid-bile duct cancers between December 2007 and June 2017. The Cox proportional hazard model was used to verify the cutoff value of the R0 resection margin. The patients were divided into 3 groups according to resection margin status (group 1; R0 resection margin ≥5 mm; group 2, R0 resection margin <5 mm; and group 3, R1 resection margin). RESULTS: The median follow-up period of the study cohort was 24 months. A resection margin of 5 mm in length was verified to be suitable as a reliable cutoff value. The median disease-free and overall survival (OS) periods were 32 and 49 months in group 1, 13 and 20 months in group 2, and 23 and 30 months in group 3, respectively (p = 0.03 and p < 0.001). The length of the tumor-free resection margin (hazard ratio, 2.01; 95% confidence interval, 1.10-3.67; p = 0.022) was independent factor affecting OS. CONCLUSIONS: BDR for mid-bile duct cancer appears to be a feasible surgical option in selected patients with careful preoperative imaging assessment and intraoperative frozen-section diagnosis. Our results suggest achieving a BDR margin ≥5 mm to improve survival outcomes.

Targeted therapy response in early versus late recurrence of renal cell carcinoma after surgical treatment: A propensity score-matched study using the Korean Renal Cancer Study Group database.

OBJECTIVES: To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma. METHODS: Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared. RESULTS: Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first-line progression-free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first-line progression-free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively). CONCLUSIONS: Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.

Clinical factors that influence the occurrence of symptomatic pseudoaneurysms and arteriovenous fistulas after partial nephrectomy: multi-institutional study of renal function outcomes after one year of selective arterial embolization

ABSTRACT Purpose: Renal artery pseudoaneurysms (RAPs) and arteriovenous fistulas (AVFs) are rare but potentially life-threatening complications after partial nephrectomy (PN). Selective arterial embolization (SAE) is an effective method for controlling RAPs/AVFs. We assessed the clinical factors affecting the occurrence of RAPs/AVFs after PN and the effects of SAE on postsurgical renal function. Materials and Methods: Four hundred ninety-three patients who underwent PN were retrospectively reviewed. They were placed in either the SAE or the non-SAE group. The effects of clinical factors, including R.E.N.A.L. scores, on the occurrence of RAPs/AVFs were analyzed. The influence of SAE on the estimated glomerular filtration rate (eGFR) during the first postoperative year was evaluated. Results: Thirty-three (6.7%) patients experienced RAPs/AVFs within 8 days of the median interval between PN and SAE. The SAE group had significantly higher R.E.N.A.L. scores, higher N component scores, and higher L component scores (all, p <0.05). In the multivariate analysis, higher N component scores were associated with the occurrence of RAPs/AVFs (Odds ratio: 1.96, p=0.039). In the SAE group, the mean 3-day postembolization eGFR was significantly lower than the mean 3-day postoperative eGFR (p <0.01). This difference in the eGFRs was still present 1 year later. Conclusions: Renal tumors located near the renal sinus and collecting system were associated with a higher risk for RAPs/AVFs after PN. Although SAE was an effective method for controlling symptomatic RAPs/AVFs after PN, a procedure-related impairment of renal function after SAE could occur and still be present at the end of the first postoperative year.

Prognostic significance of sarcopenia and decreased relative dose intensity during the initial two cycles of first-line sunitinib for metastatic renal cell carcinoma.

Targeted therapy for metastatic renal cell carcinoma (mRCC) treatment requires the identification of clinically important factors that can predict the therapeutic effect. We retrospectively investigated the prognostic roles of pre-treatment sarcopenia and relative dose intensity during the initial two cycles (2c-RDI) of sunitinib treatment in patients with mRCC. In total, 41 (52.6%) patients were classified as having sarcopenia and 16 (20.5%) patients were classified with low 2c-RDI at <75%. The mean dose reduction during sunitinib treatment was higher for sarcopenic than for non-sarcopenic patients. The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in sarcopenic patients with low 2c-RDI (n = 14, 17.9%) than in non-sarcopenic patients with high 2c-RDI (n = 35, 44.9%). Multivariate analysis identified sarcopenia and low 2c-RDI as poor prognostic factors for PFS and OS. Our findings provide new insights into the prognostic role of sarcopenia and 2c-RDI for targeted therapy in mRCC.