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This study addressed the preparation and characterization of polyethylene glycol-substituted 1-methyl-imidazolium hydroxide supported on magnetic nanoparticles (MNP@PEG-ImOH) by FESEM, FT-IR, EDAX, TEM, TGA, VSM, and XRD techniques. The catalytic activity of MNP@PEG-ImOH has been examined in Knoevenagel condensation between active methylene compounds and aromatic aldehydes in aqueous medium at room temperature. Numerous benefits of the catalytic system, such as higher yields of the products, shorter reaction time, reusability and recyclability of the catalyst, simplified work-up, and more acceptable reaction conditions, have been demonstrated. It is possible to easily isolate the catalyst from the reaction mixture by an external magnet and reapply it in the consequent reactions with no remarkable loss of activity. [ABSTRACT FROM AUTHOR]

Background: Misoprostol is a well-studied medical treatment for early pregnancy loss (EPL), with success rates ranging between 70 and 90%. However, treatment failure is associated with major patient discomfort, including the need for surgical intervention to evacuate the uterus. It was previously 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. Methods: In this retrospective cohort study, we included all women who underwent medical treatment for EPL at our institute between 07/2015 and 12/2020. Treatment outcome was compared between IVF and spontaneous pregnancies. Treatment failure was defined as a need for surgical intervention, namely, dilation & curettage (D&C) and/or hysteroscopy, due to retained products of conception, which was defined as a gestational sac or endometrial thickness greater than 15 mm in a TVS scan. Results: Overall, 775 patients were included, of which 195 (169/775 = 25.1%) ultimately required surgical intervention. There was no difference between the study groups in the rate of treatment failure. However, among IVF pregnancies, the rate of emergency D&C was lower (3.6% vs. 9.8%, p = 0.001), compared to spontaneous group. Conclusion: In cases of medical treatment for EPL, IVF pregnancies had no differences in rates of treatment failure compared to spontaneous pregnancies. That being said, IVF pregnancies have lower chances to undergo emergency D&C, compared to spontaneous pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To study whether the interval between gestational age calculated using the last menstrual period (GA-LMP) and gestational age calculated via ultrasound (GA-US) is correlated with the success rate of medical treatment in cases of miscarriages. Methods: This was a retrospective cohort study conducted in a gynecology unit in a tertiary medical center. Women who underwent medical treatment with Misoprostol for miscarriage at the Edith Wolfson Medical Center between 07/2015 and 12/2020 were included. Incomplete or septic miscarriages, multiple pregnancies, patients with irregular periods, and cases of missing data were excluded. Failure of medical treatment was defined as the need for surgical intervention due to a retained gestational sac, severe bleeding or retained products of conception. The cohort study was divided into two groups: patients with successful treatment and patients for whom surgical intervention was eventually needed. We performed both a univariate and multivariate analysis in order to identify whether a correlation between GA-LMP and GA-US interval is indeed a factor in the success rate of a medical abortion. Results: Overall, 778 patients were included in the study. From this cohort 582 (74.9%) had undergone a successful medical treatment, while 196 (25.1%) required surgical intervention due to the failure of medical treatment, as defined above. The GA-LMP to GA-US interval (in weeks) was 2.6 ± 1.4 in the success group, while the GA in the failure group was 3.1 ± 1.6 (p < 0.001). After performing a multivariant regression analysis, we were able to show that the GA-LMP to GA-US interval was found to be independently correlated with an increase in the treatment failure rate (aOR = 1.24, CI 95% (1.01–1.51), p = 0.03). Conclusions: In cases of miscarriage, longer GA-LMP to GA-US interval has been shown to be an independently correlated factor to lower success rate of the medical treatment option. [ABSTRACT FROM AUTHOR]

• Renal cell carcinoma with associated tumor thrombus poses significant surgical risk. • Current survival models are based on patients with metastatic disease, and it is not known if these are models are associated with immediate perioperative outcomes. • We found that individual clinical variables are inconsistently associated with perioperative outcomes. • Comparatively, out of the established survival models, the Moffitt Cancer Center risk stratification model is associated with more perioperative outcomes. Despite modern advances in surgical and perioperative technologies, management of renal cell carcinoma (RCC) with tumor thrombus (TT) is a morbid procedure that necessitates careful patient selection. It is not known whether established prognostic models for metastatic RCC are suitable prognostic tools for more immediate perioperative outcomes in patients with RCC with TT. We evaluated if established risk models for cytoreductive nephrectomy, as a potential extension of their purpose-built use, are associated with immediate perioperative outcomes in patients undergoing nephrectomy and tumor thrombectomy. Perioperative outcomes of patients who underwent radical nephrectomy and tumor thrombectomy for RCC were compared to presences of established predictors of long-term outcomes from prior risk models individually and as stratified by risk grouping (International Metastatic Renal-Cell Carcinoma Database Consortium [IMDC], Memorial Sloan Kettering Cancer Center [MSKCC], M.D. Anderson Cancer Center [MDACC], and Moffitt Cancer Center [MCC]). Wilcoxon rank-sum test or the Kruskal-Wallis test compared continuous variables and the chi-square test or Fisher's exact test compared categorical variables. Fifty-five patients were analyzed with 17 (30.9%) being cytoreductive. Eighteen (32.7%) patients had a level III or higher TT. Individually, preoperative variables were inconsistently associated with perioperative outcomes. Poorer risk patients per the IMDC model had more major postoperative complications (Clavien-Dindo grade≥3, P = 0.008). For the MSKCC model, poorer risk patients had increased intraoperative estimated blood loss (EBL), longer length of stay (LOS), more major postoperative complications, and more likely to discharge to a rehabilitation facility (P < 0.05). Less favorable risk patients per MDACC model had increased LOS (P = 0.038). Poorer risk patients per the MCC model had increased EBL, LOS, major postoperative complications, and 30-day hospital readmissions (P < 0.05). Overall, cytoreductive risks models were heterogeneously associated with perioperative outcomes in patients undergoing nephrectomy and tumor thrombectomy. Of available models, the MCC model is associated with more perioperative outcomes including EBL, LOS, major postoperative complications, and readmissions within 30 days when compared to the IMDC, MSKCC, and MDACC models. [ABSTRACT FROM AUTHOR]

We sought to determine whether postnephrectomy loss of renal function increases risk of recurrence and mortality in renal cell carcinoma. Retrospective analysis of 1805 patients from the International Marker Consortium for Renal Cancer registry shows de novo eGFR < 45 mL/min/1.73m2 is independently associated with progression and worsened mortality in patients aged < 65 years, underscoring desirability for nephron preservation in younger patients. Introduction: 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. Materials and Methods: 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 (eGFR < 45 mL/min/1.73m2 [eGFR < 45]) 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. Results: We analyzed 1805 patients (1113 age < 65, 692 age =65). On MVA in patients < 65, de novo eGFR < 45 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 eGFR < 45 was not independently associated with progression (P = .736), or ACM (P = .286). Comparing patients with de novo eGFR < 45 vs. eGFR =45, KMA demonstrated worsened 5-year PFS and OS in patients < 65 (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). Conclusion: Development of de novo eGFR < 45 was associated with more profound impact on patients < 65 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. [ABSTRACT FROM AUTHOR]

The accuracy of insulators and their defect identification by UAVs (unmanned aerial vehicles) in transmission-line inspection needs to be further improved, and the model size of the detection algorithm is significantly reduced to make it more suitable for edge-end deployment. In this paper, the algorithm uses a lightweight GhostNet module to reconstruct the backbone feature extraction network of the YOLOv4 model and employs depthwise separable convolution in the feature fusion layer. The model is lighter on the premise of ensuring the effect of image information extraction. Meanwhile, the ECA-Net channel attention mechanism is embedded into the feature extraction layer and PANet (Path Aggregation Network) to improve the recognition accuracy of the model for small targets. The experimental results show that the size of the improved model is reduced from 244 MB to 42 MB, which is only 17.3% of the original model. At the same time, the mAp of the improved model is 0.77% higher than that of the original model, reaching 95.4%. Moreover, the mAP compared with YOLOv5-s and YOLOX-s, respectively, is improved by 1.98% and 1.29%. Finally, the improved model is deployed into Jetson Xavier NX and run at a speed of 8.8 FPS, which is 4.3 FPS faster than the original model. [ABSTRACT FROM AUTHOR]

Purpose: 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). Materials and methods: 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). Results: 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%). Conclusion: TAE monotherapy of the primary tumor in patients with RCC improves symptomatology such as pain and hematuria with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

The role of lymphadenectomy in localized renal cell carcinoma (RCC) remains controversial. We sought to develop a preoperative nomogram called NODESAFE (NODE SAFEty) to predict;nodal tropism (NT) defined as nodes invasion at the histological report (NI) or nodes metastasis (NM) at follow up. We conducted a retrospective analysis of the INMARC database of RCC patients who underwent primary surgical resection. Patients with clinical metastasis at presentation were excluded. NM was defined as development of a new adenopathy greater than 10mm at the CT scan during follow-up. NODESAFE model was constructed through a stepwise multivariable logistic regression (MLR) model. Accuracy was tested with receiver operator characteristic estimated area under the curve (AUC). Internal validation was performed through cross validation analysis. 2,297 patients met inclusion criteria. On MLR: cN (OR 5.90, p<0.001), tumor size≥6cm (OR 3.04, p<0.001), c-reactive protein≥8.5mg/L (OR 1.98, p=0.011), neutrophile-lymphocyte ratio≥2.5 (OR 1.74, p=0.034), low enhancement in CT imaging (OR 2.05, p=0.009), hypertension (OR 2.78, p<0.001) and Charlson Comorbidity Index≥6 (OR 2.57, p=0.001) were independent predictors for NT. NODESAFE model was constructed from these variables;(Figure 1).;AUC was 0.87 (Figure 2) and 0.84 after cross validation analysis. NODESAFE risk calculator is available at http://nodesafe.pythonanywhere.com/. 3.9% threshold probabilities displayed 73.5% sensitivity, 84.5% specificity and 98.8% negative predictive value. Combining clinical features, serum biomarkers and radiographic findings, we developed a model capable of predicting with accuracy nodes tropism. NODESAFE may refine clinical decision making with respect to the performance of lymphadenectomy at the time of surgery, post-surgical surveillance, and spur consideration for adjuvant therapy. [ABSTRACT FROM AUTHOR]

Future generations of magnetic random access memory demand magnetic tunnel junctions that can provide simultaneously high magnetoresistance, strong retention, low switching energy, and small cell size below 10 nm. Here, we study perpendicular magnetic tunnel junctions with composite free layers, where multiple ferromagnet/nonmagnet interfaces can contribute to the thermal stability. Different nonmagnetic materials (MgO, Ta, and Mo) have been employed as the coupling layers in these multi-interface free layers. The evolution of junction properties under different annealing conditions is investigated. A strong dependence of the tunneling magnetoresistance on the thickness of the first CoFeB layer has been observed. In junctions where Mo and MgO are used as coupling layers, a large tunneling magnetoresistance above 200% has been achieved after 400 °C annealing. [ABSTRACT FROM AUTHOR]

• The "obesity paradox" is not an observable phenomenon across different renal cortical tumors. • Obesity is not associated with improved survival and recurrence in nonclear cell renal cell carcinoma (RCC) and in nonmetastatic clear cell RCC while metastatic clear cell RCC patients with obesity had improved oncological outcomes, due to an increased metabolic reserve and associated heightened inflammatory state which could amplify treatment responses. To investigate impact of body mass index (BMI) on survival across different histologies and stages of renal cell carcinoma (RCC). We conducted a retrospective multicenter analysis of clear cell (ccRCC) and non-ccRCC. Obesity was defined according to the WHO criteria (non-Asian BMI >30 Kg/m2, Asian BMI >27.5 Kg/m2). Multivariable analysis (MVA) via Cox regression model was conducted for all-cause (ACM), cancer-specific mortality (CSM) and recurrence. A total of 3,880 patients with a median follow-up of 31 (IQR 9–64) months were analyzed. Overall, 1,373 (35.3%) were obese; 2,895 (74.6%) were ccRCC and 985 (25.3%) were non-ccRCC (chRCC 246 [24.9%], pRCC 469 [47.6%] and vhRCC 270 [27.4%]). MVA in ccRCC revealed obesity associated with decreased risk of ACM, CSM and recurrence (hazard ratio [HR] 0.80, P = 0.044; HR 0.71, P = 0.039; HR 0.73, P = 0.012, respectively), while in non-ccRCC was not associated with decreased risk of ACM, CSM, and recurrence (P = 0.84, P = 0.53, P = 0.84, respectively). Subset analysis in stage IV ccRCC demonstrated obesity as associated with a decreased risk of ACM, CSM, and recurrence (HR 0.68, P = 0.04; HR 0.59, P = 0.01; HR 0.59, P = 0.01, respectively), while in stage I–III ccRCC was not (P = 0.21; P = 0.30; P = 0.19, respectively). Our findings refute a broad "obesity paradox" for RCC. Obesity was not associated with improved survival in non-ccRCC and in nonmetastatic ccRCC, while metastatic ccRCC patients with obesity had improved survival outcomes. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is an inflammatory marker whose elevation has been associated with worsened outcomes in renal cell carcinoma (RCC). Most studies have focused on pre-treatment values however, and there is a dearth of literature on impact of CRP dynamics. We sought to evaluate the impact of C-reactive protein dynamics (CRP) in Renal Cell Carcinoma (RCC) as biomarker for recurrence. We conducted a two center retrospective analysis of patients undergoing surgery for RCC.;;In all patients presenting for surgery, CRP was collected pre-operatively and postoperatively at 3 months, 6 months, then annually thereafter. The most recent CRP before recurrence was used to calculate delta CRP (postoperative– preoperative-CRP). Cut-point analysis employing concordance probability method was performed to determine the thresholds for preoperative CRP and delta CRP. Based on the ROC analysis, patients were stratified by preoperative CRP [low ≤1.5 mg/L (LCRP) vs. high >1.5mg/L (HCRP)], and by delta-CRP ≤1.5 mg/L (low-delta) vs. >1.5mg/L high-delta. Primary outcome was predictors of recurrence and secondary outcome was overall survival (OS). Multivariable analysis (MVA) via Cox regression was fitted for predictor of recurrence and all-cause mortality (ACM). Kaplan-Meier analysis (KMA) was assessed to compare this stratification for progression free (PFS) and overall survival (OS). 1932 patients were analyzed [LCRP/low-delta 773 (40.1%), LCRP/high-delta 292 (15.1%), HCRP/low-delta 689 (35.6%), HCRP/high-delta 178 (9.2%)]. MVA showed that LCRP/high-delta (HR 2.02, p<0.001), HCRP/low-delta (HR 1.7, p<0.001), and HCRP/high-delta (HR 2.28, p<0.001) were independent predictors associated with increased risk of recurrence. MVA for ACM demonstrated HCRP/low-delta (HR 2.64, p<0.001) and HCRP/high-delta (HR 4.89, p<0.001), associated with increased risk of mortality while LCRP/low-delta was not (p=0.32). 5 years PFS (Figure 1) was 91.1% for LCRP/low-delta, 86.5% for LCRP/high-delta, 80.7% for HCRP/low-delta and 73.% for HCRP/high-delta (p<0.001). 5-year OS (Figure 2) was 96.1% for LCRP/low-delta, 94.9% for LCRP/high-delta, 85.7% for HCRP/low-delta and 76.8% for HCRP/high-delta (p<0.001) Our findings suggest that CRP-kinetics is an independent predictor of worsened survival outcomes and recurrence, as such might may thus identify a subgroup of patients in which closer follow up or consideration for adjuvant therapy may be of benefit. Further investigation is requisite. [ABSTRACT FROM AUTHOR]

To create and;validate;U.N.I.K.;(Urologic Non-neoplastic Investigation of Kidneys), a model capable of predicting the probability of benign lesion at final histological report in patients suspected of renal cell carcinoma (RCC). We quired the INMARC database for cT1/2 renal neoplasms who underwent surgery. Primary objective was the development of a model (U.N.I.K.) capable of predicting benign renal lesions (angiomyolipoma, oncocytoma and other benign neoplasia) through a stepwise multivariable logistic regression (MLR) model. Secondary outcomes include internal validation through cross validation, decision curve analysis (DCA) and calibration plot. Overall, 3,093were analyzed [2,876 RCC (92.9%) vs. 217 benign histology (7.1%)]. On MLR female sex (OR 2.36, p<0.001), diabetes mellitus (OR 2.90, p<0.001), tumor size<3cm (OR 3.56, p<0.001), preoperative-CRP<1mg/L (OR 1.77, p<0.001), preoperative-eGFR>100 mL/min/1.73m2;(OR 3.01, p<0.001), preoperative-platelet counts≥255×109/L (OR 1.48, p=0.017), preoperative calcium≥9.34mg/dL (OR 2.39, p<0.001), Charlson Comorbidity Index<3 (OR 1.78, p=0.005) and cystic lesion (OR 17.32, p<0.001) as independent predictors of benign lesion. U.N.I.K. nomogram was constructed from these predictors;(Figure 1a).;AUC (Figure 1b) of the model was 0.85, and 0.81;;after cross validation analysis. DCA and calibration plot are depicted in;Figure 2a-2b. 7% threshold probability showed 74.7% sensitivity, 80.1% specificity and 97.7% negative predictive value. Combining clinical features, serum biomarkers and radiographic findings, we have developed a point of care model (U.N.I.K.) capable of predicting, with significant accuracy, benign tumor in patients with cortical renal neoplasms being considered for surgical resection. U.N.I.K. nomogram may refine clinical decision making with respect to identification of patients with increased likelihood of benign tumor histology and reduce burden of surgical overtreatment. External validation is requisite. [ABSTRACT FROM AUTHOR]

We compared survival outcomes and predictors in patients with upstaged T3a Renal Cell Carcinoma (RCC) versus non-upstaged pT3a RCC, as comparison of pathologically-upstaged T3a RCC and T3a RCC which was not upstaged has not been performed. We conducted a multicenter retrospective analysis. Patients were classified as cT1/cT2 RCC upstaged (pT3a-US) or non-upstaged (cT3a/pT3a-NUS). Primary outcome was All-Cause Mortality (ACM). Secondary outcomes were Cancer-Specific Mortality (CSM), and Recurrence. Multivariable Cox regression analysis (MVA) were conducted for outcomes. Kaplan-Meier Analyses (KMA) were conducted to compare Overall (OS), Cancer-Specific (CSS), and Recurrence-Free Survival (RFS), in pT3a-US and pT3a-NUS. We analyzed 879 patients [pT3a-US 69; pT3a-NUS 188;;median follow-up 48 months]. MVA for ACM demonstrated increasing tumor size (HR 1.07, p=0.022), high-grade (HR2.74, p<0.001) as independent risk factors. MVA for CSM demonstrated increasing tumor size (HR 1.11, p=0.005), high-grade (HR 2.36, p=0.003), and positive margin (HR 5.58, p=0.007) as independent predictors. MVA for recurrence revealed increasing tumor size (HR 1.05, p=0.05), high-grade (HR 3.55, p<0.001), and positive margin (HR 3.44, p<0.001) as independent predictors. pT3a-US was not an independent predictor in ACM (p=0.204), CSM (p=0.711), or recurrence (p=0.934). Comparing pT3a-NUS vs. pT3a-US, KMA revealed no difference in 5-year OS (60% vs. 62%, p=0.378), and worsened 5-year CSS and RFS were worse for pT3a-NUS (51% vs. 61%, p=0.04; 42% vs. 63%, p<0.001; Figure). Pathological upstaging is not an independent predictor of survival outcomes. In T3a RCC increasing tumor size and high-grade or presence of positive margin are main drivers of survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO)., Materials and Methods: This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs., Results: Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9)., Conclusions: IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era., (© The Author(s) 2023. Published by Oxford University Press.)

Background: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC)., Methods: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups., Results: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019)., Conclusions: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer., Competing Interests: Disclosure The authors of this study have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: Tumors with a high nephrometry score represent a challenging surgical scenario for which robotic partial nephrectomy (RPN) is a primary option in expert hands., Objective: To compare perioperative and functional outcomes of off-clamp and on-clamp RPN in patients with renal masses with a high RENAL score (≥9)., Design, Setting, and Participants: For this retrospective analysis, an RPN data set including 1604 patients treated at three institutions between 2003 and 2021 was queried for cases with a RENAL score ≥9., Outcome Measurements and Statistical Analysis: We used 1:1 propensity score matching (PSM) to select a cohort in which imbalances between the off-clamp and on-clamp groups were minimized. We used χ 2 and Student t tests to compare categorical and continuous variables, respectively. The Kaplan-Meier method was used to compare the probability of having an estimated glomerular filtration rate (eGFR) ≥45 ml/min during follow-up. Univariable and multivariable analyses were performed to identify predictors of a trifecta outcome (negative surgical margin status, no Clavien-Dindo grade ≥3 complications, eGFR decline ≤30%) and of retaining eGFR ≥45 ml/min over time., Results and Limitations: From an overall cohort of 354 patients (142 on-clamp, 212 off-clamp), a homogeneous PSM cohort of 78 patients in each group was selected (p ≥ 0.17). In the PSM cohort, operative time was significantly shorter in the off-clamp group (p < 0.001). There were no differences between the groups in the rates of severe complications (p = 0.32) and positive surgical margins (p = 0.24). The rate of trifecta achievement was significantly higher in the off-clamp group (83.3% vs 67.9%; p = 0.03). Warm ischemia time >20 min was independently negatively associated with trifecta achievement (odds ratio 0.32, 95% confidence interval 0.14-0.74). Moreover, the off-clamp group had a significantly higher probability of retaining eGFR ≥45 ml/min over time (3 yr: 95.9% vs 81.6%; p = 0.03); every 1-min increase in warm ischemia time reduced this probability by 1.3%., Conclusions: We found a favorable trade-off between the benefits and risks of off-clamp RPN, with similar perioperative outcomes and a net benefit in terms of trifecta achievement and long-term renal function outcomes in comparison to on-clamp RPN., Patient Summary: The complexity of surgery for kidney tumors can be assessed using the RENAL score, which is a measure of the location and size of a kidney tumor. In a multicenter series of patients with tumors with a high RENAL score, we compared outcomes between strategies with (on-clamp) and without (off-clamp) clamping of kidney blood vessels during robot-assisted removal of part of the affected kidney. We found that off-clamp surgery results in better postoperative kidney function., (Copyright © 2023 European Association of Urology. All rights reserved.)

Purpose of Review: To discuss role of different diagnostic imaging modalities in differentiation of benign testicular masses from seminomatous germ cell tumors (SGCTs) and non-seminomatous GCTs (NSGCTs)., Recent Findings: New modalities of ultrasonography, including contrast enhancement and shear wave elastography, may help differentiate between benign and malignant intratesticular lesions. Ultrasonography remains the recommended imaging modality for initial evaluation of testicular masses. However, MRI can be used to better define equivocal testicular lesions on US., (© 2023. The Author(s).)

Introduction: 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., Materials and Methods: 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 (eGFR<45 mL/min/1.73m2 [eGFR<45]) 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., Results: We analyzed 1805 patients (1113 age<65, 692 age≥65). On MVA in patients <65, de novo eGFR<45 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 eGFR<45 was not independently associated with progression (P=.736), or ACM (P=.286). Comparing patients with de novo eGFR<45 vs. eGFR ≥45, KMA demonstrated worsened 5-year PFS and OS in patients <65 (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)., Conclusion: Development of de novo eGFR<45 was associated with more profound impact on patients <65 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., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To review the current status of surgical and procedural treatments for renal cell carcinoma (RCC), focusing on oncological and functional outcomes, and the use of techniques for advanced disease over the last 10 years., Findings: Partial nephrectomy (PN) has become the reference standard for most T1 and T2 masses. In cT2 RCC, PN exhibits oncological equivalence and improved functional outcomes compared to radical nephrectomy (RN). Additionally, emerging data suggest that PN may be used to treat cT3a RCC. The robot-assisted platform is increasingly used to treat locally advanced RCC. Studies suggest safety and feasibility of robotic RN and robotic inferior vena cava tumor thrombectomy. Additionally, single-port robot-assisted laparoscopic approaches are comparable to multiport approaches in select patients. Long-term data show that cryoablation, radiofrequency ablation, and microwave ablation are equipotent in management of small renal masses. Emerging data suggest that microwave may effectively treat cT1b masses., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Dhanji et al.)

As the indications for the use of immunotherapy in genitourinary malignancies expand, its role in combination with standard or conventional therapies has become the subject of contemporary studies. Radiotherapy has multiple immunomodulating effects on anti-tumor immune response, which highlights potential synergistic role with immunotherapy agents. We sought to review the body of published data studying the combination of immunotherapy and radiotherapy as well as the rationale for combination therapy. Trial information and primary articles were obtained using the following terms "immunotherapy", "radiotherapy", "prostate cancer", and "bladder cancer." All articles and trials were screened to ensure they included combination radiotherapy and immunotherapy. The effects of radiation on the immune system, including both immunogenic and immunosuppressive effects, have been reported. There is a potential for combinatorial or synergistic effects between radiation therapy and immunotherapy in treating bladder and prostate cancers. However, results from ongoing and future clinical trials are needed to best integrate immunotherapy into current standard of care treatments for GU cancers.

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Several markers of inflammation have been associated with oncologic outcomes. Prognostic markers are not well-defined for renal cell carcinoma (RCC). We sought to investigate the association of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and De Ritis ratio with mortality in RCC., Methods: Multi-center retrospective analysis of patients undergoing surgery for RCC. Primary outcome of interest was all-cause mortality (ACM). Secondary outcomes were non-cancer mortality (NCM) and cancer-specific mortality (CSM). Elevated NLR was defined as ≥2.27, elevated PLR as ≥165, and elevated De Ritis ratio as ≥ 2.72. Multivariable cox regression analysis (MVA) was conducted to elucidate risk factors for primary and secondary outcomes, and Kaplan-Meier analysis (KMA) was used to evaluate survival outcomes comparing elevated and non-elevated NLR, PLR, and De Ritis ratio., Results: 2656 patients were analyzed (874 patients had elevated NLR; 480 patients had elevated PLR and 932 patients had elevated De Ritis). Elevated NLR was a significant predictor of ACM (HR 1.32, 95% CI: 1.07-1.64, p=0.003) and NCM (HR 1.79, 95% CI: 1.30-2.46, p<0.001) in MVA. Elevated De Ritis was a significant predictor of ACM (HR 2.04, 95% CI: 1.65-2.52), NCM (HR 1.84, 95% CI: 1.33-2.55, p<0.001), and CSM (HR 1.97, 95% CI:1.48-2.63, p<0.001). KMA revealed significant difference in 5-year overall survival (OS) (48% vs. 68%, p<0.001), non-cancer survival (NCS) (69% vs. 87%, p<0.001), and cancer-specific survival (CSS) (60% vs. 73%, p<0.001) for elevated versus non-elevated NLR. For PLR, there was a difference in 5-year OS (51% vs. 61%, p<0.001) and CSS (60% vs. 73%, p<0.001) with KMA., Conclusions: Elevated NLR was independently associated with worse ACM and NCM, while elevated De Ritis was predictive for CSM in addition to ACM and NCM. These differences may be useful in refining risk stratification with respect to cancer-related and non-cancer mortality in RCC patients and deserve further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Keiner, Meagher, Patil, Saito, Walia, Liu, Dutt, Miller, Dhanji, Saidian, Wan, Yasuda, Fujii, Tanaka, Master, Derweesh.)

Purpose: We sought to evaluate outcomes of lymph node dissection (LND) in patients with upper tract urothelial carcinoma., Materials and Methods: We performed a multicenter retrospective analysis utilizing the ROBUUST (for RObotic surgery for Upper Tract Urothelial Cancer Study) registry for patients who did not undergo LND (pNx), LND with negative lymph nodes (pN0) and LND with positive nodes (pN+). Primary and secondary outcomes were overall survival (OS) and recurrence-free survival (RFS). Multivariable analyses evaluated predictors of outcomes and pathological node positivity. Kaplan-Meier analyses (KMAs) compared survival outcomes., Results: A total of 877 patients were analyzed (LND performed in 358 [40.8%]/pN+ in 73 [8.3%]). Median nodes obtained were 10.2 for pN+ and 9.8 for pN0. Multivariable analyses noted increasing age (OR 1.1, p <0.001), pN+ (OR 3.1, p <0.001) and pathological stage pTis/3/4 (OR 3.4, p <0.001) as predictors for all-cause mortality. Clinical high-grade tumors (OR 11.74, p=0.015) and increasing tumor size (OR 1.14, p=0.001) were predictive for lymph node positivity. KMAs for pNx, pN0 and pN+ demonstrated 2-year OS of 80%, 86% and 42% (p <0.001) and 2-year RFS of 53%, 61% and 35% (p <0.001), respectively. KMAs comparing pNx, pN0 ≥10 nodes and pN0 <10 nodes showed no significant difference in 2-year OS (82% vs 85% vs 84%, p=0.6) but elicited significantly higher 2-year RFS in the pN0 ≥10 group (60% vs 74% vs 54%, p=0.043)., Conclusions: LND during nephroureterectomy in patients with positive lymph nodes provides prognostic data, but is not associated with improved OS. LND yields ≥10 in patients with clinical node negative disease were associated with improved RFS. In high-grade and large tumors, lymphadenectomy should be considered.

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 < 0.001). Mean operative time for SP cases was 183.9 ± 63.5 min vs 208.6 ± 65.0 min in the MP cohort (p = 0.12). Rate of conversion to radical nephrectomy was 3.8% vs 9.6% for SP vs MP cases, respectively, (p = 0.37). The majority of patients were discharged on postoperative day one (67.9%) irrespective of operative approach (p = 0.60). There were no differences in inpatient milligram morphine equivalents administered (MME, p = 0.08) or outpatient postoperative MME prescribed (p = 0.21) between the two cohorts. In this retrospective single-institution study, SP robotic approach offers similar short-term perioperative outcomes to MP platforms for minimally invasive, nephron-sparing surgery. Using the SP system was not associated with a reduction in postoperative opioid analgesic requirements., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

While multiple studies have demonstrated that minimally invasive surgical (MIS) techniques are a safe and efficacious approach to adrenalectomy for pheochromocytomas (PC), these studies have only been small comparative studies. The aim of this multi-institutional study is to compare perioperative outcomes between open and MIS, stratified by robotic and conventional laparoscopic, techniques in the surgical management of PC. We retrospectively evaluated patients who underwent adrenalectomy for PCs from 2000 to 2017 at three different institutions. Clinical, perioperative, and pathologic parameters were analyzed using t test, Chi square, and Fisher exact statistical measures. Of the 156 adrenalectomy cases performed, 26 (16.7%) were with an open approach and 130 (83.3%) using MIS techniques. Of the MIS procedures, 41 (31.5%) were performed robotically and 89 (68.5%) performed laparoscopically without robotic assistance. Demographic and clinical parameters were similar between the open and MIS groups. Patients, who underwent MIS procedure had a lower complication rate (p = 0.04), shorter hospitalization (p = 0.02), shorter operative time (p < 0.001), and less blood loss (p = 0.002) than those who underwent open surgical resection. Conventional laparoscopic and robotic operative approaches resulted in similar complication rates, length of hospitalization, and blood loss. Our study is one of the largest cohorts comparing the perioperative outcomes between conventional laparoscopic and robotic adrenalectomies in patients with PC. Our results support that MIS techniques have potentially lower morbidity compared to open techniques, while laparoscopic and robotic approaches have similar perioperative outcomes.

To describe our institution's initial experience with radical (RN) and partial nephrectomy (PN) using the SP robotic system. The recent FDA approval of the da Vinci ® SP robotic platform has led to its use in minimally invasive approaches to urologic malignancies. There are little data on its feasibility and safety after implementation for radical and partial nephrectomy. All patients who underwent PN or RN using the SP system at our institution were reviewed. All PNs were performed off-clamp. Patient demographics, preoperative imaging, operative approaches, and perioperative outcomes were collected and analyzed. Sixteen patients underwent PN (n = 13) or RN (n = 3) utilizing the SP robotic system between January 2019 and June 2019. Average age was 58.6 ± 13.9 and 61.0 ± 1.7 years in each group, respectively. A retroperitoneal approach was performed in 7 (53.8%) PN patients and 1 (33.3%) RN patient. A transperitoneal approach was performed in 6 (46.1%) PNs and 2 (66.7%) RNs. Mean operative time and median estimated blood loss for PN was 176.9 ± 64.0 min and 200 (50-800) ml compared to 176.3 ± 73.8 min and 50 (50-400) ml for RN. There was one operative conversion (7.7%) to an open approach in the PN group. Length of hospital stay postoperatively averaged 1.9 ± 1.3 days and 3.3 ± 1.2 days for patients undergoing partial and radical nephrectomy, respectively. SP partial and radical nephrectomies through transperitoneal and retroperitoneal approaches appear to be feasible surgical techniques in the management of cortical renal masses. Off-clamp PN is also a feasible approach using the SP system. However, further study is needed to establish its safety and use in renal surgery across multiple institutions and larger patient cohorts.

Enhanced recovery after surgery programs were developed as a type of standardized evidence-based perioperative care protocols. The necessity and benefit of clinical care pathways is not a new phenomenon in urology and have been a big part of the evolution of care for urology patients, especially in terms of urologic oncology. This article discusses the key components of evidence-based perioperative care in key urologic procedures. These protocols have been shown to decrease length of stay, decrease complications, and reduce cost., (Copyright © 2018 Elsevier Inc. All rights reserved.)