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To evaluate if trans-arterial embolization (TAE) of the primary tumor in patients with renal cell carcinoma (RCC) improves symptomatology such as pain and hematuria or oncologic outcomes such as progression-free survival (PFS) and overall survival (OS).The systematic review search included PubMed, Ovid/MEDLINE, and Embase for full-text English articles including randomized and non-randomized prospective trials as well as prospective and retrospective case series. To be included, prospective trials needed ≥ 25 patients in each arm while case series and retrospective chart reviews required at least two patients. Evaluated outcomes included PFS, OS, change in tumor size, improvements in pain, improvements in hematuria, and adverse events (AEs).1327 articles were retrieved and screened. Nine studies met inclusion criteria (retrospective case series, n = 8; non-randomized prospective trial, n = 1) which included 237 patients (M = 156 (65.8%); F = 56 (23.6%); gender unreported = 25 (10.5%); mean age: 69.4 (range: 38-87)) with a mean tumor diameter of 9.3 cm (5.2-10.5). When reported, the TNM stages were stage I (n = 10), II (n = 18), III (n = 36), and IV (n = 121). 60 patients were treated for pain and hematuria. After TAE, pain improved in 59 patients (98.3%) and hematuria improved in 57 patients (95%). A meta-analysis for improvements in pain and hematuria demonstrated an event rate of pain improvement of 0.952 (0.788-0.990; p 0.001) and an event rate for hematuria improvement of 0.923 (0.809-0.971; p 0.001). Median OS ranged from 1 to 39 months but only one study reported PFS (10.5 months). Only one study demonstrated a statistically significant improvement in OS with TAE when compared with patients that did not undergo TAE (p = 0.02). A reduction in tumor size was only achieved in 17 patients (17/49; 34.7%) limiting evaluation. AEs included fever (n = 115/237; 48.5%), flank pain (n = 72/237; 30.4%), nausea (n = 58/237; 24.5%), hematuria (n = 12/237; 5.1%), hypertension (n = 12/237; 5.1%), reduced GFR (n = 6/237; 2.5%), hematoma (n = 6/237,2.5%), and ileus (n = 3/237; 1.3%).TAE monotherapy of the primary tumor in patients with RCC improves symptomatology such as pain and hematuria with an acceptable safety profile.

Translating preclinical studies to effective treatment protocols and identifying specific therapeutic responses in individuals with cancer is challenging. This may arise due to the complex genetic makeup of tumor cells and the impact of their multifaceted tumor microenvironment on drug response. To find new clinically relevant drug combinations for colorectal cancer (CRC), we prioritized the top five synergistic combinations from a large in vitro screen for ex vivo testing on 29 freshly resected human CRC tumors and found that only the combination of mitogen-activated protein kinase kinase (MEK) and proto-oncogene tyrosine-protein kinase Src (Src) inhibition was effective when tested ex vivo. Pretreatment phosphorylated Src (pSrc) was identified as a predictive biomarker for MEK and Src inhibition only in the absence of KRAS

Purpose of review To review the current literature and guidelines regarding salvage therapy for local and regional recurrence of primary penile cancer. Recent findings While invasive surgical management has not significantly changed, penile sparing treatments (PSTs) may have a promising role in the management of local recurrence. Penile sparing surgeries do appear to have higher rates of recurrence. However, the overall survival rate is comparable to that of partial and total penectomies. Additionally, a combination of therapies may have a more profound effect on management of penile cancer. Summary Clinicians must discuss the role of each type of therapy for penile cancer with their patients, and tailor their management to the extent of disease in each patient. While it is important to discuss the balance between quality of life and rates of relapse, one must also emphasize the rates of overall survival in patients with local recurrence who are treated with PSTs.

A review of advertisement studies shows that there has been little attempt to examine infomercials in terms of rhetorical appeals and persuasive strategies. Therefore, this study sought to contribute to the existing literature by exploring the persuasive elements of Apple infomercials through Aristotle’s modes of persuasion to reveal the most frequent persuasive language features and structures and to study how such elements were utilized to promote the products and services of the company. A top-down approach based on Aristotle’s modes of persuasion was adopted to identify the rhetorical appeals of logos, ethos and pathos as well as the promotional tokens and patterns in the text. The descriptive findings provided evidence to demonstrate that although all the rhetorical proofs were employed in the corpus, emotional appeal was the most dominant. The findings of this research open new horizons for further studies on infomercials in general and persuasive rhetoric in specific.

We sought to determine whether loss of renal function increases risk of recurrence and metastases in renal cell carcinoma (RCC), and whether this impact was age-related.We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry. Patients were separated into younger (65 years old) and elder (≥65 years old) age groups, and rates of de novo estimated glomerular filtration rate (eGFR45 mL/min/1.73m2 [eGFR45]) were calculated. Multivariable analysis (MVA) was conducted for predictors of progression-free survival (PFS) and all-cause mortality (ACM). Kaplan-Meier Analysis (KMA) was conducted for PFS and overall survival (OS) in younger and elder age groups stratified by functional status.We analyzed 1805 patients (1113 age65, 692 age≥65). On MVA in patients65, de novo eGFR45 was independently associated with greater risk for worsened progression (HR=1.61, P=.038) and ACM (HR=1.82, P=.018). For patients ≥65, de novo eGFR45 was not independently associated with progression (P=.736), or ACM (P=.286). Comparing patients with de novo eGFR45 vs. eGFR ≥45, KMA demonstrated worsened 5-year PFS and OS in patients65 (PFS: 68% vs. 86%, P.001; OS: 73% vs. 90%, P.001), while in patients ≥65, only 5-year OS was worsened (77% vs. 81%, P.021).Development of de novo eGFR45 was associated with more profound impact on patients65 compared to patients ≥65, being an independent risk factor for PFS and ACM. The mechanisms of this phenomenon are unclear but underscore desirability for nephron preservation when safe and feasible in younger patients.

Evidence supporting the safe use of the single-port (SP) robot for partial nephrectomy is scarce. The purpose of this study was to compare perioperative outcomes for patients undergoing robotic assisted SP vs multi-port (MP) partial nephrectomy (PN) in a time-matched cohort. All patients with clinically localized renal masses who underwent robotic PN from January 2019 to March 2020 were evaluated. Patients were stratified according to SP vs MP approach. Postoperative analgesia was administered in accordance with department-wide opioid stewardship protocol and outpatient opioid use was tracked. Total of 78 patients underwent robotic PN with 26 patients in the SP cohort. The majority of renal masses had low-complexity (53, 67.9%) R.E.N.A.L. nephrometry scores, without a significant difference between the two cohorts (p = 0.19). A retroperitoneal approach was performed in 16 (20.5%) patients overall, though more commonly via the SP robotic approach (13 vs 3, p

Background: Misoprostol is a well-studied medical treatment for early pregnancy loss (EPL), with success rates ranging between 70-90%. However, treatment failure is associated with major patient discomfort, including the need for surgical intervention to evacuate the uterus. It was reported that medical treatment was especially successful among women who conceived after in vitro fertilization (IVF). We aimed to study if there is a difference in rates of medical treatment failures for EPL between pregnancies conceived by IVF and spontaneous pregnancies. This is a retrospective cohort study. Methods: All women who underwent medical treatment for EPL at our institute between 07/2015 and 12/2020 were included. The cohort was divided into two groups: IVF and spontaneous pregnancies.Treatment failure was defined as any surgical intervention, namely, dilation & curettage (D&C) and/or hysteroscopy, due to retained products of gestation. Baseline characteristics and failure rates were compared between the groups.Results: Overall, 775 patients were included, of which 195 (25.1%) ultimately required surgical intervention. There was no difference between the groups in the rate of treatment failure. However, among the IVF group, the rate of emergency D&C was lower (3.6% vs. 9.8%, p=0.001) compared to the spontaneous group. Conclusion: In cases of medical treatment for EPL, IVF pregnancies have lower chances to undergo emergency D&C, compared to spontaneous pregnancies. Overall, there are no differences in rates of treatment failure between IVF and spontaneous pregnancies.

To evaluate effects of worsening surgically induced chronic kidney disease (CKD-S) on oncological and non-oncological survival outcomes in renal cell carcinoma (RCC).We performed a retrospective analysis of patients who underwent partial (PN) or radical nephrectomy (RN) and were free of preoperative CKD (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 mWe analysed 3239 patients. The mean preoperative and last-follow-up eGFRs were 87.4 and 69.5 mL/min/1.73 mDevelopment of CKD-S Stage 3b and 4, but not 3a, was associated with worsened ACM and NCM. The decision to proceed with nephron preservation via PN should be individualised based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3a.

Introduction Liquid biopsies utilize cell-free DNA (cfDNA) in blood plasma or urine across various applications, including cancer detection, treatment selection, and treatment/minimal residual disease monitoring. Higher amplifiable copies recovered from liquid biopsies can lead to better cancer detection and monitoring. In this study, we evaluated the recovery of cfDNA amplifiable copies and circulating tumor DNA (ctDNA) dynamics using the nRichDX extraction method, which can extract cfDNA from a broad range of biological fluids (1mL - 20mL). cfDNA quality and ctDNA dynamics were assessed using Liquid IQ and UltraSEEK on the MassARRAY System. Methods Whole blood from healthy donors was collected in K2EDTA tubes, and plasma was isolated and then pooled in preparation for cfDNA extraction. Plasma aliquots at 5mL (6) and 20mL (6) were extracted using the Revolution Max20 cfDNA Extraction Kit. (12) replicate samples were extracted using QiAmp Circulating Nucleic Acid Kit. Half of the samples were spiked with a cfDNA standard containing a KRAS p.G12V mutation. The quantity and quality of extracted cfDNA were determined using the Liquid IQ panel on the MassARRAY system, which measures amplifiable cfDNA copies, high/low molecular weight dynamics, white blood cell (WBC) contamination along with a molecular barcode for sample matching. Recovery and frequency of the spiked ctDNA standard were performed with the UltraSEEK Lung V2 Panel, capable of detecting variants as low as 0.1% allele frequency. Results This study compared the amplifiable copies recovered from cfDNA extracted using the nRichDX and Qiagen kit. The amplifiable copies for the nRichDX and Qiagen methods, respectively, were: 5mL non-spiked 517+/-36 Vs. 398+/-17, 5mL spiked 946+/-99 Vs. 732+/-73; 20mL non-spiked 1526+/-26 Vs. 1071+/-55 and 20mL spiked 3004+/-278 Vs. 1777+/-207. All results were statistically different by conventional criteria, evaluated by a two-tailed t-test. Other cfDNA quality characteristics, such as low/high molecular weight DNA and WBC contamination, were concordant between the 2 methods. The spiked KRAS mutation was recovered consistently by both methods with a mutation frequency (5.3+/-0.3) and mutation significance z-score (296+/-19). Conclusion The nRichDX Revolution System extracts cfDNA and ctDNA with consistently high yields. Two sample T-Test analysis shows that nRichDX, at all levels, performed significantly better than Qiagen at p < 0.05. The results demonstrate the capability of the nRichDX system to recover more amplifiable copies with consistent cfDNA quality and ctDNA frequency and hence offer the opportunity to increase the sensitivity of detecting lower frequency mutations in cfDNA and a wider variety of biomarkers. Citation Format: Nafiseh Jafari, Mayer Saidian, Darryl Irwin. The nRichDX ® revolution sample prep system enables recovery of more amplifiable copies and more cancer fraction detection from cfDNA as evaluated on the MassARRAY ® System [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6600.

Data regarding the clinical outcomes of men with metastatic hormone sensitive prostate cancer (mHSPC) who harbor homologous recombination repair (HRR) gene alterations have not been fully characterized. Here, we examine a cohort of mHSPC patients who underwent genomic sequencing to evaluate the impact of HRR gene alterations on time to castrate resistance and other outcomes. We found that the presence of an HRR gene alteration is associated with a shorter time to mCRPC. INTRODUCTION: The homologous recombination repair (HRR) pathway is a frequently mutated pathway in advanced prostate cancer. The clinical course of patients with HRR gene alterations who have metastatic hormone sensitive prostate cancer (mHSPC) has not been fully characterized. Here, we examine the outcomes of men with mHSPC with HRR alterations. METHODS: We conducted a single-center retrospective analysis of men with mHSPC who underwent next generation sequencing. The primary objective was to assess the time from diagnosis of mHSPC to metastatic castrate resistance prostate cancer (mCRPC) in patients with pathogenic HRR alterations compared to individuals lacking these alterations. Key secondary objectives included time to mCRPC in prespecified cohorts, PSA response, and overall survival. RESULTS: 151 men with mHSPC were identified for the study. 24% (N = 37) had pathogenic HRR gene alterations detected with the most common alterations found in BRCA2 (n = 15), ATM (n = 10), and CDK12 (n = 7). Time to mCRPC was significantly decreased in patients with HRR gene alterations versus those without such alterations (12.7 vs. 16.1 months, HR 1.95, P = .02). In multivariate analysis, the effect of HRR gene alterations on time to CRPC remained significant when adjusting for age, mHSPC therapy, the volume of disease, the presence of visceral metastases, and PSA (adjusted HR 1.69, P = .02). Stratified by specific HRR gene alteration, patients with BRCA2 or CDK12 had significantly decreased time to mCRPC compared to other HRR alterations. CONCLUSION: HRR gene alterations are associated with the worse outcomes in mHSPC with significantly shorter time to mCRPC. Given the established role of Poly (ADP-ribose) Polymerase (PARP) inhibitors in mCRPC, these data highlight an opportunity to examine PARP inhibitors earlier in the clinical course for prostate cancer patients. Ongoing prospective studies will further validate the role of PARP inhibitors in mHSPC patients.