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Purpose: To determine the degree of renal function deterioration after renal cryoablation in patients with a solitary functioning kidney on the basis of ablation volume., Materials and Methods: Over a 15-year period, 81 percutaneous cryoablations were performed in solitary functioning kidneys. After exclusion of patients with baseline end-stage renal disease (ESRD) and insufficient follow-up, analysis was performed on 65 procedures in 52 patients (40 men; mean age, 63.5 years). The postcryoablation renal function was based on the lowest serum creatinine within 6 months after procedure. Renal function change was defined as percentage glomerular filtration rate (GFR) change. Volumetric analysis was performed on the target lesion, renal parenchyma, and ablation zone., Results: The median tumor diameter was 2.0 cm (range, 0.8-4.7 cm). The median baseline GFR decreased from 56.4 mL/min/1.73 m 2 (range, 17.5-89.7 mL/min/1.73 m 2 ) to 46.9 mL/min/1.73 m 2 (range, 16.5-89.7 mL/min/1.73 m 2 ) at median of 95 days (P < .001), equating to a -7.9% median renal function change (range, -45.0% to +30.7%). All patients had Stage 2 or worse chronic kidney disease, and baseline function did not correlate with renal function change. The median volume of ablated parenchyma was 19.7 mL (range, 2.4-87.3 mL), equating to 8.1% (range, 0.7%-37.2%) of total parenchyma. The volume of parenchymal volume ablated correlated significantly with renal function loss, whereas age, hypertension, and diabetes mellitus did not. No patient developed ESRD within 1 year after cryoablation., Conclusions: Cryoablation in solitary functioning kidneys resulted in a modest reduction in renal function, even in patients with chronic kidney disease and ablations of up to 20% of renal parenchymal volume., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Background: The effect of radical nephroureterectomy (RNUx) on postoperative renal function in patients diagnosed with upper tract urothelial carcinoma (UTUC) has not been thoroughly explored., Methods: We conducted a retrospective analysis including 785 patients who underwent RNUx for UTUC. We assessed the preoperative and postoperative estimated glomerular filtration rates (eGFRs) and factors related to the decline in eGFR. Additionally, we examined the effect of comorbidities (diabetes or hypertension) on the postoperative eGFR at 1 year. Cox proportional hazard models were employed to investigate the clinical effect of RNUx on oncological outcomes, including non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS)., Results: The median preoperative and postoperative eGFR levels were 54.7 and 40.6 ml/min/1.73 m 2 respectively. The proportions of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m 2 were 35.9% and 5.1%, respectively. The median decline in the eGFR after surgery was 26.8%. Patients with preoperative eGFR <60 ml/min/1.73 m 2 demonstrated significantly lower odds of a postoperative decline in eGFR of 25% or more. The effect of comorbidities on postoperative eGFR at 1 year was significant (P = 0.048). The 3-year NUTRFS, CSS, and OS rates were 72.9%, 85.2%, and 81.5%, respectively. Preoperative chronic kidney disease was an independent factor associated with inferior NUTRFS, CSS, and OS., Conclusion: Different degrees of impairment of renal function occur among UTUC patients. Only 5.1% of patients retain a postoperative eGFR ≥60 ml/min/1.73 m 2 . Preoperative renal impairment was linked to reduced odds of postoperative eGFR decrease and associated with survival. In addition, the presence of comorbidities had a significant effect on the decline in eGFR. These findings emphasize the importance of developing evidence-based perioperative treatment strategies for UTUC patients with impaired renal function., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To assess the effect of cryoablation on renal function (measured by estimated glomerular filtration rate [eGFR] or serum creatinine) for treating Stage I renal cancer., Materials and Methods: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were systematically searched from inception to May 1, 2023. Cohort studies that included data on change of eGFR and serum creatinine increase were included. Meta-analysis was performed by measuring the weighted mean difference and by fitting random-effect models., Results: Overall, 38 studies were included, comprising 3,202 participants. Percutaneous cryoablation was associated with an absolute eGFR reduction of -3.06 mL/min/1.73 m 2 (95% CI, -4.12 to -2.01; P < .001) and serum creatinine increase of 0.05 mg/dL (95% CI, -0.02 to 0.11; P > .05). The weighted absolute mean difference of percutaneous cryoablation for treating Stage T1b renal cell carcinoma was estimated at -5.19 mL/min/1.73 m 2 (95% CI, -11.1 to 0.72; P > .05). Lastly, when analyzing studies that included cohorts with solitary kidneys, the pooled weighted mean difference was estimated as -3.27 mL/min/1.73 m 2 (95% CI, -6.79 to 0.25; P > .05)., Conclusions: Percutaneous cryoablation for Stage 1 renal cell carcinoma has minimal significant impact on renal function (measured by eGFR or serum creatinine). The same outcome was observed in patients with larger tumors (T1b) and those with solitary kidneys., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Renal cell carcinoma is difficult to diagnose and unpredictable in disease course and severity. There are no specific biomarkers for diagnosis and prognosis estimation feasible in clinical practice. Long non-coding RNAs (lncRNAs) have emerged as potent regulators of gene expression in recent years. Aside from their cellular role, their expression patterns could be used as a biomarker of ongoing pathology., Methods: In this work, we used next-generation sequencing for global lncRNA expression profiling in tumor and non-tumor tissue of RCC patients. The four candidate lncRNAs have been further validated on an independent cohort. PVT1, as the most promising lncRNA, has also been studied using functional in vitro tests., Results: Next-generation sequencing showed significant dysregulation of 1163 lncRNAs; among them top 20 dysregulated lncRNAs were AC061975.7, AC124017.1, AP000696.1, AC148477.4, LINC02437, GATA3-AS, LINC01762, LINC01230, LINC01271, LINC01187, LINC00472, AC007849.1, LINC00982, LINC01543, AL031710.1, and AC019197.1 as down-regulated lncRNAs; and SLC16A1-AS1, PVT1, LINC0887, and LUCAT1 as up-regulated lncRNAs. We observed statistically significant dysregulation of PVT1, LUCAT1, and LINC00982. Moreover, we studied the effect of artificial PVT1 decrease in renal cell line 786-0 and observed an effect on cell viability and migration., Conclusion: Our results show not only the diagnostic but also the therapeutic potential of PVT1 in renal cell carcinoma., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Objective: To analyze predictors, extent and functional implications associated with renal parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) prior to intervention. This phenomenon is well-recognized yet not adequately studied, and, if severe, can influence management., Materials and Methods: A retrospective review was performed of partial nephrectomy (PN) and radical nephrectomy (RN) patients with available preoperative nuclear-renal-scan and imaging demonstrating solitary RCC with normal contralateral kidney. Normal renal parenchymal volume of each kidney was measured by free-hand scripting from preoperative axial images. Primary endpoint was percent PVR which was estimated assuming that the contralateral-kidney serves as a control: PVR = (volume contralateral kidney - volume ipsilateral kidney) normalized by volume contralateral kidney. Multivariable linear-regression analysis assessed factors associated with preoperative PVR. Further analysis evaluated the functional effect of PVR prior to surgery., Results: 146 PN and 136 RN patients with necessary studies were analyzed. For RN, the median PVR was 15% and a quarter of patients had PVR ≥27%. In contrast, PVR was negligible in PN patients for whom median preoperative parenchymal volumes were nearly identical in the ipsilateral/contralateral kidneys (179/180cc, respectively). PVR inversely correlated with preoperative renal function in the ipsilateral kidney (P <.01). Tumor-size (P <.01), stage (P = .03), and endophytic properties (P = .03) associated with PVR on multivariable-analysis., Conclusion: Our data suggest that substantial replacement of normal parenchyma by RCC occurs in many patients selected for RN and can contribute to preexisting renal-insufficiency. PVR prior to intervention is mainly driven by tumor characteristics in RN patients, but is negligible in most PN patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To study the natural history of renal oncocytomas and address indications for intervention by determining how growth is associated with renal function over time, the reasons for surgery and ablation, and disease-specific survival., Patients and Methods: The study was conducted in a retrospective cohort of consecutive patients with renal oncocytoma on active surveillance reviewed at the Specialist Centre for Kidney Cancer at the Royal Free London NHS Foundation Trust (2012 to 2019). Comparison between groups was performed using Mann-Whitney U-tests and chi-squared tests. A mixed-effects model with a random intercept for patient was used to study the longitudinal association between tumour size and estimated glomerular filtration rate (eGFR)., Results: Longitudinal data from 98 patients with 101 lesions were analysed. Most patients were men (68.3%) and the median (interquartile range [IQR]) age was 69 (13) years. The median (IQR) follow-up was 29 (26) months. Most lesions were small renal masses, and 24% measured over 4 cm. Over half (64.4%) grew at a median (IQR) rate of 2 (4) mm per year. No association was observed between tumour size and eGFR over time (P = 0.871). Nine lesions (8.9%) were subsequently treated. Two deaths were reported, neither were related to the diagnosis of renal oncocytoma., Conclusion: Natural history data from the largest active surveillance cohort of renal oncocytomas to date show that renal function does not seem to be negatively impacted by growing oncocytomas, and confirms clinical outcomes are excellent after a median follow-up of over 2 years. Active surveillance should be considered the 'gold standard' management of renal oncocytomas up to 7cm., (© 2021 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: In recent years, the controlled nutritional status (CONUT) score has been widely recognized as a new indicator for assessing survival in patients with urological neoplasms, including renal, ureteral, and bladder cancer. However, the CONUT score has not been analyzed in patients with HIV-related urological neoplasms. Therefore, we aimed to evaluate the prognostic significance of the CONUT score in patients with HIV-related renal cell carcinoma (RCC)., Methods: A total of 106 patients with HIV-related RCC were recruited from four hospitals between 2012 and 2021, and all included patients received radical nephrectomy or partial nephrectomy. The CONUT score was calculated by serum albumin, total lymphocyte counts, and total cholesterol concentrations. Patients with RCC were divided into two groups according to the optimal cutoff value of the CONUT score. Survival analysis of different CONUT groups was performed by the Kaplan-Meier method and a log rank test. A Cox proportional risk model was used to test for correlations between clinical variables and cancer-specific survival (CSS), overall survival (OS), and disease-free survival (DFS). Clinical variables included age, sex, hypertension, diabetes, tumor grade, Fuhrman grade, histology, surgery, and CD4+ T lymphocyte count., Result: The median age was 51 years, with 93 males and 13 females. At a median follow-up of 41 months, 25 patients (23.6%) had died or had tumor recurrence and metastasis. The optimal cutoff value for the CONUT score was 3, and a lower CONUT score was associated with the Fuhrman grade (P=0.024). Patients with lower CONUT scores had better CSS (HR 0.197, 95% CI 0.077-0.502, P=0.001), OS (HR 0.177, 95% CI 0.070-0.446, P<0.001) and DFS (HR 0.176, 95% CI 0.070-0.444, P<0.001). Multivariate Cox regression analysis indicated that a low CONUT score was an independent predictor of CSS, OS and DFS (CSS: HR=0.225, 95% CI 0.067-0.749, P=0.015; OS: HR=0.201, 95% CI 0.061-0.661, P=0.008; DFS: HR=0.227, 95% CI 0.078-0.664, P=0.007). In addition, a low Fuhrman grade was an independent predictor of CSS (HR 0.192, 95% CI 0.045-0.810, P=0.025), OS (HR 0.203, 95% CI 0.049-0.842, P=0.028), and DFS (HR 0.180, 95% CI 0.048-0.669, P=0.010), while other factors, such as age, sex, hypertension, diabetes, tumor grade, histology, surgery, and CD4+ T lymphocyte count, were not associated with survival outcome., Conclusion: The CONUT score, an easily measurable immune-nutritional biomarker, may provide useful prognostic information in HIV-related RCC., 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 © 2021 Xue, Zhang, Wang, Zhang and Hu.)

Background: In patients with genitourinary cancers, the effect of immune checkpoint inhibitors (ICIs) on kidney function is unknown., Patients and Methods: This is a retrospective cohort study of patients with renal cell carcinoma (RCC) and urothelial carcinoma who received ICIs at two major cancer centers between 2012 and 2018. Cumulative incidence and Fine and Gray subdistribution hazard models were performed to determine predictors of the co-primary outcomes, (1) acute kidney injury (AKI) and (2) sustained estimated glomerular filtration rate (eGFR) loss, defined as a >20% decline in eGFR sustained ≥90 days. We also determined the association between immune-related adverse events (irAE) and adverse kidney outcomes among patients surviving ≥1 year., Results: 637 patients were included; 320 (50%) patients had RCC and 317 (50%) patients had urothelial carcinoma. Half of the cohort had eGFR<60 mL/min/1.73 m 2  at baseline. irAEs, AKI, and sustained eGFR loss were common, occurring in 33%, 25% and 16%, respectively. Compared to patients with urothelial carcinoma, patients with RCC were more likely to develop irAEs (aHR 1.61, 95% CI 1.20-2.18) and sustained eGFR loss (aHR 1.97, 95% CI 1.24-3.12), but not AKI (aHR 1.53, 95% CI 0.97-2.41). Among patients surviving ≥1 years, experiencing a non-renal irAE was associated with a significantly higher risk of sustained eGFR loss (aHR 1.71, 95% CI 1.14-2.57)., Conclusion: AKI and sustained eGFR loss are common in patients with genitourinary cancers receiving ICIs. irAEs may be a novel risk factor for kidney function decline among patients receiving ICIs., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HS, SS, IA, ML, SZ, NR, DC, DEL, KR, CS, MDK, MES have nothing to declare. OR: Research support from Merck. Speaker for activities supported by educational grants from BMS and Merck. Consultant for Merck, Celgene, Five Prime, GSK, Bayer, Roche/Genentech, Puretech, Imvax, Sobi. In addition, Dr. Rahma has a patent “Methods of using pembrolizumab and trebananib” pending. BM: discloses payment for consulting with Bayer, Astellas, Astra Zeneca, Seattle Genetics, Exelixis, Nektar, Pfizer, Janssen, Genentech, Eisai, BMS, Calithera, Dendreon and EMD Serono. He received research support to Dana Farber Cancer Institute (DFCI) from Bristol Myers Squibb, Calithera, Exelixis, Seattle Genetics. GS: Advisory Board: BMS, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, Astrazeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Immunomedics; Research Support to Institution: Sanofi, Astrazeneca, Immunomedics; Travel costs: BMS, Astrazeneca; Speaking fees: Physicians Education Resource (PER), Onclive, Research to Practice, Medscape; Writing fees: Uptodate, Editor of Elsevier Practice Update Bladder Cancer Center of Excellence; Steering committee of trials/studies: BMS, Bavarian Nordic, Seattle Genetics, QED (all unpaid), and Astrazeneca, EMD Serono, Debiopharm (paid). SM: Salaried position as a Deputy Editor at UpToDate (Wolters Kluwer). SG: scientific coordinator for the ASCEND trial. XG: Honorarium from Exelixis. XW: Research support to Institution: BMS. MDM - MD Advisory Board for Pfizer, Exelixis, Eisai and Merck. TKC - AstraZeneca, Aveo, Bayer, Bristol Myers-Squibb, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi/Aventis, Takeda (institutional and personal) related to research, consultancy and advisory boards. TKC is supported in part by the Dana Farber/Harvard Cancer Center Kidney SPORE Program, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at DFCI., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To describe the safety and efficacy of partial nephrectomy (PN) in comparison to radical nephrectomy (RN) for surgically managed renal hilar tumors., Materials and Methods: We retrospectively reviewed institutional records of patients with a small (<5 cm) solitary renal (hilar or non-hilar) mass who underwent PN or RN between 2008 and 2018. Hilar tumors were defined as those at medial position, abutting the renal vessels. Recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier method., Results: Of 1,951 eligible patients, 399 had hilar tumors (292 scheduled for PN, 107 RN) and 1,552 had non-hilar tumors (scheduled for PN). We found no significant differences in survival measures between hilar and non-hilar tumors in patients selected for PN. Patients scheduled for PN for hilar tumors had higher rates of ≥grade II postoperative surgical complications compared to patients scheduled to receive PN for non-hilar tumors (13% vs 8.6%; log-rank P = .018) and non-statistically significantly elevated rates of ≥grade II complications compared to patients scheduled for RN for hilar tumors (13% vs 6.5%; difference 6%, 95% CI 0.4%, 13%; log-rank P = .07)., Conclusion: PN for hilar and non-hilar renal masses (<5cm) experience comparable oncologic outcomes though increased risk of complications for hilar masses. PN for hilar tumors was associated with better renal function and overall survival with non-statistically elevated risk of grade II or higher complications than RN. A renal tumor located at the hilum should not be a contra-indication for performing PN., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The presence of sarcomatoid features and/or lymph node-positive disease may be associated with a worse prognosis in chromophobe renal cell carcinoma (ChRCC). We sought to better characterize patients' long-term outcomes with these features compared with those without these features., Materials and Methods: We identified 300 patients treated for sporadic, unilateral, nonmetastatic ChRCC between 1993 and 2019. Clinical and pathologic features were summarized, and cancer-specific survival (CSS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier plots. Cox regression analysis was performed to determine factors associated with recurrence. Patients with sarcomatoid features and/or nodal disease were grouped as high-risk in a secondary analysis., Results: The median age was 60 years, 43.7% were female, 29.3% had pT3/T4 disease, 3.3% had sarcomatoid features, and 4% had pathologic N1 disease. Sixteen patients were categorized as high-risk based on the presence of sarcomatoid features (n = 4), pathologic N1 disease (n = 6), or both (n = 6). There were 22 recurrences; the recurrence rate in the low-risk group was 4.9% and 50% in the high-risk group. 10-year RFS was 91.4% in the low-risk group and 34.4% in the high-risk group (P < 0.001). 10-year CSS was 96.4% in the low-risk group and 54.3% in the high-risk group (P < 0.001). In multivariable analysis, sarcomatoid features (HR 5.5, CI 1.5-20.2, P = 0.01) and pN1 disease (HR 16.5, CI 5.3-51.4, P < 0.0001) were independently associated with RFS., Conclusions: The presence of sarcomatoid features and/or lymph node-positive disease portends a poor prognosis in ChRCC. Further studies evaluating the impact of novel therapeutic agents in these patients are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of the present study was to explore the effect of chaperon‑mediated autophagy (CMA) through pyruvate kinase isoform M2 (PKM2) on the development of renal carcinoma (RCC) and its possible mechanisms. Lysosome‑associated membrane protein 2A (LAMP‑2A) and PKM2 expression levels were detected by collecting tissue samples from RCC patients. RNA interference was used to silence the LAMP‑2A and PKM2 expression levels in renal cell line A498 to detect the proliferation, apoptosis and invasion of cells. The levels of mRNA and protein of related genes were also examined. Co‑immunoprecipitation was used to detect the interaction between PKM2 and heat shock cognate 70 (HSC70). The results revealed that LAMP‑2A and PKM2 expression levels were significantly increased in RCC tissues and cell lines (P<0.01). LAMP‑2A silencing increased the expression level of PKM2 in A498 and 786‑O cells. LAMP‑2A and PKM2 silencing suppressed the proliferation and invasion and induced the apoptosis of A498 cells, and also affected the expression levels of related genes. Co‑immunoprecipitation revealed the interaction between PKM2 and HSC70. In conclusion, CMA could affect the proliferation, invasion and apoptosis of RCC cells through PKM2, and our findings provided new biomarkers and targets for molecular targeted therapy of RCC.

Extracellular vesicles (EVs) represent a diverse group of small membrane-encapsulated particles involved in cell-cell communication, but the technologies to characterize EVs are still limited. Hypoxia is a typical condition in solid tumors, and cancer-derived EVs support tumor growth and invasion of tissues by tumor cells. We found that exposure of renal adenocarcinoma cells to hypoxia induced EV secretion and led to notable changes in the EV protein cargo in comparison to normoxia. Proteomics analysis showed overrepresentation of proteins involved in adhesion, such as integrins, in hypoxic EV samples. We further assessed the efficacy of time-gated Raman spectroscopy (TG-RS) and surface-enhanced time-gated Raman spectroscopy (TG-SERS) to characterize EVs. While the conventional continuous wave excitation Raman spectroscopy did not provide a notable signal, prominent signals were obtained with the TG-RS that were further enhanced in the TG-SERS. The Raman signal showed characteristic changes in the amide regions due to alteration in the chemical bonds of the EV proteins. The results illustrate that the TG-RS and the TG-SERS are promising label free technologies to study cellular impact of external stimuli, such as oxygen deficiency, on EV production, as well as differences arising from distinct EV purification protocols., (© 2021. The Author(s).)

Purpose: To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients., Materials and Methods: A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987-2018). Descriptive and survival analyses were performed., Results and Limitations: Median age at VHL diagnosis was 34 years (IQR 25-43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79 months (IQR 0-132), and median index tumor size leading to treatment was 35.5 mm (IQR 28-60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4 cm. With a median follow-up of 8 years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10 years, respectively. Overall mortality was 4% and 7.5% at 5 and 10 years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up., Conclusions: Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Chronic renal failure is one of the most challenging complications after the completed surgical treatment for renal cell cancer. In 2016, a grading system of tumorous renal involvement was developed, referred to as NCIU nephrometry. However, the systematic parameter to reflect the functional status of the functional renal parenchyma is defined by tumor volume only, with no regard for spatial disposition of the segment(s) where the tumor is located. Our research team decided to improve the NCIU nephrometry system by developing and testing a modified formula for calculation of creatinine clearance, which makes allowance for spatial disposition of tumor within the kidney. We performed numerical computations and analysis of changes in functional status of renal parenchyma depending on coordinate-based spatial location of the tumor in order to augment the existing NCIU nephrometry scale; Matlab, a specialized software package was used as a principal instrument to calculate the number of nephrons and functional renal parenchyma depending on the coordinate-based position of the mass center of the tumor and tumor volume. This model was shown to create a feasible opportunity to increase the percentage of organ-sparing procedures for renal cell cancer and to reduce the incidence/progression of chronic renal failure in these patients.

Purpose of Review: To compare laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) performed in two European tertiary centers using the classic optimal surgical definition - "MIC" - and a new optimal surgical definition: the "Novel TRIFECTA" (NT) concept. We sought to strengthen the PN evidence and to test the NT's performance., Recent Findings: The study population comprehended 505 cases of localized kidney cancer from two tertiary centers between 2012 and 2019. The NT achievement was higher in the RAPN group when compared to LPN (70.5 vs. 87.4%; p = 0.004), while no differences were found when considering the MIC criteria. Also, a similar high-grade complications rate (Clavien-Dindo > III) and operative time (105 min vs. 100 min; p = NS) were found. In the multivariable regression, the RAPN approach was a predictor of NT achievement (OR 2.45; p = 0.008). NT achievement was higher in the RAPN group, while similar results were found when evaluating the MIC criteria. The NT definition could be more sensitive to the individual-specific responses related to the PN.

Purpose: Preoperative estimation of new baseline glomerular filtration rate after partial nephrectomy or radical nephrectomy for renal cell carcinoma has important clinical implications. However, current predictive models are either complex or lack external validity. We aimed to develop and validate a simple equation to estimate postoperative new baseline glomerular filtration rate., Materials and Methods: For development and internal validation of the equation, a cohort of 7,860 patients with renal cell carcinoma undergoing partial nephrectomy/radical nephrectomy (2005-2015) at the Veterans Affairs National Health System was analyzed. Based on preliminary analysis of 94,327 first-year postoperative glomerular filtration rate measurements, new baseline glomerular filtration rate was defined as the final glomerular filtration rate within 3 to 12 months after surgery . Multivariable linear regression analyses were applied to develop the equation using two-thirds of the renal cell carcinoma Veterans Administration cohort. The simplest model with the highest coefficient of determination (R 2 ) was selected and tested. This model was then internally validated in the remaining third of the renal cell carcinoma Veterans Administration cohort. Correlation/bias/accuracy/precision of equation were examined. For external validation, a similar cohort of 3,012 patients with renal cell carcinoma from an outside tertiary care center (renal cell carcinoma-Cleveland Clinic) was independently analyzed., Results: New baseline glomerular filtration rate (in ml/minute/1.73 m 2 ) can be estimated with the following simplified equation: new baseline glomerular filtration rate = 35 + preoperative glomerular filtration rate (× 0.65) - 18 (if radical nephrectomy) - age (× 0.25) + 3 (if tumor size >7 cm) - 2 (if diabetes). Correlation/bias/accuracy/precision were 0.82/0.00/83/-7.5-8.4 and 0.82/-0.52/82/-8.6-8.0 in the internal/external validation cohorts, respectively. Additionally, the area under the curve (95% confidence interval) to discriminate postoperative new baseline glomerular filtration rate ≥45 ml/minute/1.73 m 2 from receiver operating characteristic analyses were 0.90 (0.88, 0.91) and 0.90 (0.89, 0.91) in the internal/external validation cohorts, respectively., Conclusions: Our study provides a validated equation to accurately predict postoperative new baseline glomerular filtration rate in patients being considered for radical nephrectomy or partial nephrectomy that can be easily implemented in daily clinical practice.

To evaluate the validity of CHAC1 for predicting the prognosis of kidney renal clear cell carcinoma (KIRC) and to explore its therapeutic potential for KIRC, we conducted several bioinformatic analyses using the sequencing data and clinical information derived from online databases. We found CHAC1 is down-regulated in KIRC samples when compared with normal samples but up-regulated in KIRC samples with relatively higher malignancy and later stages. Univariate cox analysis and multivariate cox regression analysis were conducted and the results revealed up-regulated CHAC1 is an independent risk factor for poor prognosis of KIRC. Further, the nomogram model based on the result of multivariate cox regression analysis was constructed and effectively predicted patients' 1-year, 3-year and 5-year survival respectively. The correlation analyses showed CHAC1 is associated with the immune pathway markers of memory B cell, natural killer cell and type1 T helper cell as well as the checkpoint genes like ADORA2A, CD200, CD44, CD70, HHLA2, NRP1, PDCD1LG2 and TNFRSF18. Furthermore, experiments in vitro indicated CHAC1 could induce cell death in KIRC cell lines but had limited influence on cell migration and cell invasion. In conclusion, CHAC1 is found a valid indicator for poor prognosis of kidney renal clear cell carcinoma., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Surgical treatments for renal cell carcinoma reduces kidney volume to some degree and may derive postsurgical chronic kidney disease. We made a new marker for postoperative renal function using CT volumetry. To determine the impact of various parameters including this marker, we observed pre- and postsurgical renal function of experienced cases., Methods: From 2004 to 2014, we underwent total or partial nephrectomy for 181 patients with renal carcinoma in a single institution. Of the total, 138 cases with presurgical CT volumetry were included in this study. We evaluated parameters for assessments of peri- and postoperative renal function including age, gender, serum creatinine, eGFR, performed surgery, pathology, estimated residual kidney volume and associated disease. Presence or absence of acute kidney injury (AKI) and chronic kidney disease (CKD) were also evaluated before, immediately after and 5 years after surgery., Results: Multiple logistic regression analysis identified AKI, preoperative eGFR and estimated residual kidney volume as significant prognostic factors for the postoperative CKD. Moreover, cases with triple positive of these factors suffer postoperative CKD more significantly than those with one or two positives., Conclusion: Using these predictive factors, we may determine patients with high risk for CKD who require an early intervention of renal protective treatment.

Objective: To compare the surgical outcomes between the transperitoneal (TP) and retroperitoneal (RP) approaches in robot-assisted laparoscopic partial nephrectomy (RAPN) for lateral tumors., Methods: This study included patients who underwent RAPN for lateral renal tumors between 2013 and 2019. Lateral tumors were defined as X of A factors in the RENAL nephrometry score. In total, 290 and 48 patients with TP and RP, respectively, were included in the analysis. To minimize the effects of selection bias, the following variables were adjusted using 1:1 propensity score matching: age, sex, body mass index, American Society of Anesthesiologists score, preoperative estimated glomerular filtration rate, tumor size, and RENAL nephrometry score., Results: After matching, 48 patients were allocated to each group. The mean age was 55 years, and the mean preoperative estimated glomerular filtration rate (eGFR) was 68-69 mL/min/1.73 m 2 . The mean tumor size was 30-31 mm. The RP group had a shorter operative time (124 vs. 151 min, p = 0.0002), shorter console time (74 vs. 110 min, p < 0.0001), shorter warm ischemic time (14 vs. 17 min, p = 0.0343), lower estimated blood loss (EBL) (33 vs. 52 ml, p = 0.0002), and shorter postoperative length of hospital stay (PLOS) (3.3 vs. 4.0 days, p < 0.0001) than the TP group. The change in eGFR, incidence rate of perioperative complication, and positive surgical margin rate did not significantly differ between the two groups., Conclusion: RP had better surgical outcomes, including shorter operative time, lower EBL, and shorter PLOS for lateral renal tumors, which may suggest that RP is the optimal approach for selected lateral renal tumors.

Purpose: It remains unclear whether a short warm ischemic time (WIT) improves long-term renal function after partial nephrectomy (PN) for patients with pre-existing chronic kidney disease (CKD). We evaluated renal function after PN according to WIT duration in patients with stage III CKD., Materials and Methods: We identified 277 patients with stage III CKD who underwent PN during 2004-2017. Propensity score matching was used to created two matched groups of patients: Group A (WIT of <25 min) and Group B (WIT of ≥25 min). The outcomes of interest were longitudinal kidney function change, new-onset stage IV CKD (eGFR <30 mL/min/1.73 m 2 ) and overall survival., Results: The two matched groups contained 85 patients each. The median follow-up durations were 49 months in Group A and 42 months in Group B. The median pre-treatment eGFRs were 52.4 mL/min/1.73 m 2 in Group A and 52.6 mL/min/1.73 m 2 in Group B. There were no differences in kidney function between the two groups throughout the follow-up period (P > 0.05). The 5-year rates of new-onset stage IV CKD were not significantly different between Group A and Group B (8.2% vs. 7.1%), with no significant difference in the risk of developing stage IV CKD in Group A (vs. group B, hazard ratio: 0.527, 95% confidence interval: 0.183-1.521; P = 0.236). The 5-year overall survival rates were 90.3% for Group A and 96.2% for Group B (P = 0.549)., Conclusions: A short WIT was not associated with better postoperative kidney function or survival after PN in patients with stage III CKD., Competing Interests: Declaration of competing interest All the authors declare no potential conflict of interest to disclose., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Despite using prognostic algorithms and standard surveillance guidelines, 17% of patients initially diagnosed with low risk clear cell renal cell carcinoma (ccRCC) ultimately relapse and die of recurrent disease, indicating additional molecular parameters are needed for improved prognosis., Results: To address the gap in ccRCC prognostication in the lower risk population, we performed a genome-wide analysis for methylation signatures capable of distinguishing recurrent and non-recurrent ccRCCs within the subgroup classified as 'low risk' by the Mayo Clinic Stage, Size, Grade, and Necrosis score (SSIGN 0-3). This approach revealed that recurrent patients have globally hypermethylated tumors and differ in methylation significantly at 5929 CpGs. Differentially methylated CpGs (DMCpGs) were enriched in regulatory regions and genes modulating cell growth and invasion. A subset of DMCpGs stratified low SSIGN groups into high and low risk of recurrence in independent data sets, indicating that DNA methylation enhances the prognostic power of the SSIGN score., Conclusions: This study reports a global DNA hypermethylation in tumors of recurrent ccRCC patients. Furthermore, DMCpGs were capable of discriminating between aggressive and less aggressive tumors, in addition to SSIGN score. Therefore, DNA methylation presents itself as a potentially strong biomarker to further improve prognostic power in patients with low risk SSIGN score (0-3).

Introduction: The diffusion-weighted imaging (DWI) technique with intravoxel incoherent motion model enables the estimation of capillary blood volume as a perfusion-related parameter- (PP-) value. Therefore, the PP-value of the kidney theoretically reflects renal capillary blood volume. We analyzed the usefulness of the PP-value in estimating postoperative renal function in upper-tract urothelial carcinoma (UTUC) patients., Methods: Forty-eight consecutive patients who underwent magnetic resonance imaging before radical nephroureterectomy from 2011 to 2018 were analyzed. A PP-map displaying PP-values on a pixel-by-pixel basis was created from DWI signals (b-values of 0, 500, and 1,000 s/mm2). Two readers independently analyzed the renal PP-value. DWI-based split renal function (SRF) of the intact kidney was calculated by splitting serum Cr-based preoperative estimated glomerular filtration rates (eGFRs). The predictive accuracy of the method was evaluated using renography as the reference standard., Results: Interobserver analysis revealed an excellent correlation value of 0.97. The SRF value showed a good linear correlation with the observed postoperative eGFR (r = 0.76, p < 0.001). The predictive accuracy of the DWI-based method was similar to that of the nuclear-based method., Conclusion: This DWI-based evaluation of capillary blood volume provides a noninvasive tool for predicting the postoperative renal function, thereby facilitating the management of UTUC patients., (© 2021 S. Karger AG, Basel.)

Background: Nephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease., Methods: To determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6-12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria., Results: Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m 2 ), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence., Conclusions: After a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy., (Copyright © 2020 by the American Society of Nephrology.)

Background: Glomerular hyperfiltration is associated with all-cause mortality. Herein, we evaluated the association between glomerular hyperfiltration and the development of cancer, the most common cause of death, in an Asian population., Methods: We retrospectively reviewed the National Health Insurance Service database of Korea for people who received national health screenings from 2012 to 2013. Glomerular hyperfiltration was defined as the 95th percentile and greater after stratification by sex and age decile. We performed a multivariate Cox regression analysis using glomerular hyperfiltration at the first health screening as the exposure variable and cancer development as the outcome variable to evaluate the impact of glomerular hyperfiltration on the development of cancer., Results: A total of 1,953,123 examinations for patients with a median follow-up time of 4.4 years were included in this study. Among the 8 different site-specific cancer categories, digestive organs showed significant associations between glomerular hyperfiltration and cancer. The population with glomerular hyperfiltration showed an increased risk for stomach cancer [adjusted hazard ratio (aHR) = 1.22], colorectal cancer (aHR = 1.16), and liver or intrahepatic malignancy (aHR = 1.35)., Conclusions: Glomerular hyperfiltration was associated with an increased risk for the development of cancer in specific organs, such as the stomach, colorectum, and liver and intrahepatic organ., Impact: Glomerular hyperfiltration needs to be considered a significant sign of the need to evaluate the possibility of hidden adverse health conditions, including malignancies., (©2020 American Association for Cancer Research.)

Background: There is some evidence to suggest that endogenous levels of sex hormones might influence the etiology of cancers of the pancreas, kidney, and brain, but epidemiologic data are lacking., Methods: We evaluated the association of circulating levels of total and free testosterone, and of sex hormone-binding globulin (SHBG), with the risk of cancers of the pancreas, kidney, and brain, and of total and free estradiol with the risk of kidney cancer, in the UK Biobank cohort study ( n = 425,793; 225 pancreatic cancers, 749 kidney cancers, 467 brain cancers). Multivariable Cox proportional hazards models were used to estimate HRs and 95% confidence intervals for the associations., Results: Testosterone and SHBG levels were not associated with risk of pancreatic cancer. Most of the associations for the other two anatomic sites were null. There were inverse associations between total testosterone and brain cancer in men and between SHBG and risk of kidney cancer in the total sample and in women. Estradiol was not associated with the risk of kidney cancer., Conclusions: The results of this study provide little support for associations between sex hormones/SHBG and risk of cancers of the pancreas, kidney, and brain. Larger studies are warranted., Impact: Although these results provide little support for roles for sex hormones and SHBG in the etiology of cancers of the pancreas, kidney, and brain, there is a need for studies with larger numbers of cases., (©2020 American Association for Cancer Research.)

Our previous study identified a novel VHLα isoform which negatively modulated hnRNPA2B1 expression and therefore influenced pyruvate kinase transcript splicing in renal cancer, while the regulation and initiation of alternative translation are largely unknown. Here we unraveled the CUG-mediated translation start of VHLα, which was subjected to the regulation by both eukaryotic initiator factor eIF2A and RNA helicase eIF4A. Unexpectedly, we found hnRNPA2B1 promoted VHLα alternative translation as well via direct interaction with its octadic pentamer region of VHL transcript. The N-terminal of VHLα was indispensable in mediating ubiquitination of hnRNPA2B1 at lysine residues 274 and 305. We further identified aberrant overexpression of c-myc as upstream oncogenic signaling to positively regulate hnRNPA2B1 transcription in renal cancer. Therefore, our data suggested an anti-tumoral feedback loop between VHLα and hnRNPA2B1.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to kill a wide variety of tumor cells with minimal effects on normal cell. However, renal cell carcinoma (RCC) cells 786-0 and OS-RC-2 were resistant to TRAIL. The present study examines the potential of combining polyphenolic compound resveratrol (RES) with TRAIL. We found that RES can sensitize RCC cells to TRAIL-induced death. Electron microscopy analyses showed that RES plus TRAIL can induce both autophagy and apoptosis in RCC cells. It was proved that the apoptosis is caspase-dependent and the activation of caspase-8, caspase-9, and caspase-3 was involved in this process. Besides, we also found that XIAP expression was significantly inhibited after RES plus TRAIL treatment in RCC cells. Furthermore, a fiber-modified replication-deficient adenovirus Ad5/35-TRAIL was generated to test the synergistic effect of RES and TRAIL in vivo. Our data demonstrated that RES plus Ad5/35-TRAIL significantly inhibited RCC xenograft growth in nude mice. These results suggest the possibility of a new combination therapeutic leading to the improvement of RCC treatment.

Patients with renal cell carcinoma (RCC) usually develop drug resistance and have poor prognosis owing to its insensitive property. However, the underlying mechanisms of RCC are still unclear. We implemented an integrative analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets. Three genes (CRHBP, RAB25 and PSAT1) were found to be potential biomarkers in ccRCC and validated by four independent cohorts. Then, ccRCC patients with a decreased expression of CRHBP in tumor tissues had significantly poor survival by TCGA ccRCC datasets and verified by clinical samples as well as RCC cell lines. Overexpression of CRHBP suppressed cell proliferation, migration, invasion as well as apoptosis in vitro and in vivo. Moreover, the results of western blot analysis showed the effects of CRHBP via upregulating NF-κB and p53-mediated mitochondria apoptotic pathway. Our results suggested that CRHBP may be an effective target to treat ccRCC patients.

Objective: This study examined the prevalence of self-perceived burden (SPB) and its association with health-related quality of life (HRQoL) among urologic cancer patients., Methods: This was a prospective, cross-sectional study. A total of 429 respondents diagnosed with urologic cancers (prostate, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed by using a structured questionnaire. SPB and HRQoL were measured by the Self-perceived Burden Scale and the Functional Assessment of Cancer Therapy-General 7 Item Scale respectively., Results and Conclusion: Self-perceived burden was experienced by 73.2% of the respondents. Respondents who had a lower education level, a monthly household income

Purpose: Loss of renal function remains a major limitation of radical nephrectomy. The extent of renal functional compensation by the preserved kidney after radical nephrectomy has not been adequately studied in this elderly population with comorbidities., Materials and Methods: A total of 273 patients treated with radical nephrectomy without end stage renal disease with available preoperative nuclear renal scans were included in the analysis. Renal functional compensation was defined as percent change in estimated glomerular filtration rate of the preserved kidney after radical nephrectomy. Estimated glomerular filtration rate was calculated by the Chronic Kidney Disease-Epidemiology Collaboration formula up to 5 years postoperatively. Preoperative/postoperative parenchymal volumes of the preserved kidney were measured from cross-sectional imaging. Multiple regression was used to identify predictive factors for renal functional compensation., Results: Median age was 67 years and 67% of the patients were male. Overall 70% had hypertension, 26% diabetes and 37% preexisting chronic kidney disease. Locally advanced (T3a or greater) tumors were found in 53% of cases. Renal functional compensation was observed at 2 weeks (median 10%) and increased during the first 3 months (median 26%) after radical nephrectomy. Functional stability was then observed to 5 years. Renal parenchymal volume increased a median of 10% at 3 to 12 months but in addition, the functional efficiency per unit of parenchymal volume also increased 8% (estimated glomerular filtration rate units/cm 3 of parenchyma was 0.236 postoperatively vs 0.208 preoperatively, p=0.004). Age (-0.85, p <0.01), global preoperative estimated glomerular filtration rate (-0.28, p <0.01) and split renal function of the removed kidney (0.61, p <0.01) were independent predictors of renal functional compensation., Conclusions: Percent renal functional compensation after radical nephrectomy is greater in younger patients, when preoperative estimated glomerular filtration rate is lower and when the removed kidney has more robust function. Increases in measurable parenchymal mass and functional efficiency contribute substantially to renal functional compensation.

Introduction: To assess the safety and efficiency of retroperitoneal laparoscopic partial nephrectomy (RLPN) and retroperitoneal laparoscopic radical nephrectomy (RLRN) for large (≥4 cm) renal tumors with a RENAL nephrometry score ≥7., Materials and Methods: We retrospectively identified and analyzed the data of 254 patients who underwent RLPN or RLRN for large (≥4 cm) and anatomically complex renal tumors between 2008 and 2017. Propensity score matching (PSM) (1:1) method was conducted to adjust for preoperative clinical characteristics. Preoperative, renal functional, and oncological outcomes were compared., Results: Finally, no significant differences in the baseline characteristics existed between the two groups after PSM. Within the well-balanced matched cohort, longer operating time (OT) and higher estimated blood loss (EBL) were found in RLPN group (p = 0.015 and p = 0.019, respectively), and RLPN trended to protect renal function better at a higher risk of low-grade complications (-10.9 vs -16.8 ml/min, p = 0.001; 23.0% vs 10.8%, p = 0.048, respectively). The patients in the RLPN group had a better overall survival (OS) than those in RLRN group, but cancer-specific survival and progression-free survival didn't differ significantly between the two groups., Conclusion: For patients with large (≥4 cm) and anatomically complex renal tumors, RLPN by highly experienced hands has an evident tendency to a better protection of renal function and a longer OS without waiving oncological control in comparison with RLRN, but at the expense of longer OT, a higher EBL and a higher risk of low-grade complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To evaluate the renal function outcomes after selective trans-arterial embolization (SAE) of iatrogenic vascular lesions (IVL), including pseudoaneurysm and arteriovenous fistula, following partial nephrectomy (PN)., Materials and Methods: A multi-institutional study was conducted including consecutive patients who underwent PN between January 2009 and March 2019. Two surgical approaches were used: open and robot-assisted PN. Patients with SAE were identified and matched (1:2) with patients without IVL. The matching criteria were age, gender, Charlson score, creatinine clearance, RENAL score, and tumor size. The primary outcome was the evolution of global renal function at 6-months postoperatively., Results: A total of 493 consecutive PN (360 open PN and 133 robot-assisted PN) were included. IVL occurred in 17 cases (3.4%) without statistical difference according to the surgical approach (P = .78). Patients from embolization group were matched to 34 cases without postoperative IVL. Groups were comparable concerning clinical, tumor and surgical characteristics. The clinical success of SAE, defined as the absence of recourse to a second embolization or a total nephrectomy, was obtained in 16 (94.1%) cases. No minor or major complications were reported after SAE. The preoperative estimated glomerular filtration rate (eGFR) was similar between control group (93 [85-102] ml/min) and embolization group (95 [83-102] ml/min) (P = .99). Median (IQR) eGFR between control group (87 [72-95] ml/min) and embolization group (83 [76-93] ml/min) at a follow-up of 6 months showed no significant difference (P = .73)., Conclusion: IVL are rare complications of PN. SAE is an effective and minimally invasive management tool, with no deleterious effect on global renal function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors (ICIs) improve significantly outcome of patients with advanced renal cancer. Although immune-related adverse events involve frequently skin, digestive tract, lung, liver and endocrine organs, haematological toxicities are rare. We describe the case of a patient with metastatic renal cancer who was treated with nivolumab. Eight courses of nivolumab were administered without any toxicity; brain metastases were then diagnosed and treated with stereotactic radiotherapy. As the extra-cranial disease was stable, the ninth course of nivolumab was administered 5 days after the end of radiotherapy. One week later, he presented with rectal and nasal bleeding in a context of severe thrombocytopenia (1000/mm 3 ). High dose of steroids and intravenous immunoglobulin reversed slowly the thrombocytopenia. This case highlights the possibility of life-threatening thrombocytopenia with ICIs. Interestingly, the close time relation with radiotherapy highlights a potential interaction, warranting a close follow-up of patients in this situation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The standard of care for surgically resectable disease renal cell carcinoma (RCC) is a nephrectomy. Post-nephrectomy, these patients are at risk for the development of new onset chronic kidney disease or the progression of pre-existing chronic kidney disease. We aimed to report the changes in renal function in patients who had a nephrectomy for RCC., Methods: This retrospective, descriptive, cross-sectional study identified 137 patients who had a nephrectomy for RCC from 1 January 2009 to 31 December 2017. The pre-nephrectomy and post-nephrectomy estimated glomerular filtration rate (eGFR) and the histological subtype of RCC on histopathological analysis of the resected specimen were recorded from the National Health Laboratory Services online results platform. All analyses were conducted using SPSS (Version 25) and the significance level was set at p < 0.05., Results: After a mean follow-up period of 26.5 ± 22 months (median = 19 months), the patients' eGFR dropped by a mean of 4.82 ± 8.67 ml/min/1.73 m2 (95% CI 3.23-6.41) post-nephrectomy. The mean eGFR fall in patients' who had hypertension and/or diabetes ( n = 63) was significantly larger compared to patients who had neither of these comorbidities ( n = 54; p < .001; mean = 7.30 ± 8.40 ml/min/1.73 m2 (95% CI 5.19-9.42) and 1.93 ± 8.14 ml/min/1.73 m2 (95% CI 0.30-4.15) respectively., Conclusions: The decline in renal function in patients with hypertension and/or diabetes mellitus is more pronounced than in patients with neither of these comorbidities. In these high-risk patients, measures must be taken to prevent the development and limit the progression of chronic kidney disease., (Copyright© Authors.)

Renal lymphangectasia is a benign malformation of the lymphatics which can be perirenal or peripelvic in location. Diagnosis is made on imaging including ultrasound, computed tomography , or MRI. We present an unusual case of renal lymphangectasia presenting with gross hematuria and flank pain diagnosed on computed tomography., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the utility of parenchymal volume analysis (PVA) for estimation of split renal function (SRF) in patients with renal masses. SRF is important for deciding about partial vs radical nephrectomy (PN/RN) and assessing risk for developing severe chronic kidney disease after surgery. For renal donors PVA is routinely used to estimate SRF, but the utility of PVA for the more complex renal mass population remains undefined., Patients and Methods: All patients (n = 374) with renal tumours and a normal contralateral kidney managed with PN (2010-2018), with preoperative/postoperative nuclear renal scans (NRS) and cross-sectional imaging were analysed. Parenchymal volumes were measured by free-hand scripting or software analysis. Concordance between ipsilateral estimated glomerular filtration rate (eGFR) values based on SRF from NRS vs PVA were evaluated by Pearson correlation and Bland-Altman plots. Parallel analysis of all 155 patients managed with RN at our centre (2006-2016) with preoperative NRS and imaging was also performed., Results: For PN, the median age and tumour size were 62 years and 3.4 cm, respectively. The median preoperative ipsilateral parenchymal volume and eGFR were 181 cm 3 and 36.9 mL/min/1.73 m 2 , respectively. Parenchymal volumes estimated by free-hand scripting vs software analyses correlated strongly (r = 0.98, P < 0.001). Preoperative ipsilateral eGFR based on SRF from PVA vs NRS also correlated strongly (r = 0.94, P < 0.001). Ipsilateral eGFR saved after PN correlated strongly with parenchymal volume preserved (all r >0.60); however, the correlation was much stronger when ipsilateral eGFRs were based on SRF from PVA rather than NRS (z-statistic = 3.15, P = 0.002). For RN patients, preoperative eGFR in the contralateral kidney based on SRF from PVA vs NRS also correlated strongly (r = 0.87, P < 0.001)., Conclusion: PVA has utility for estimation of SRF in patients with renal masses, even though this population is older and more comorbid than renal donors and the tumour can complicate the analysis. PVA can be obtained by software analysis from preoperative cross-sectional imaging and thus readily incorporated into routine clinical practice., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Introduction and Objectives The animal models for renal carcinogenesis have allowed researchers to better understand the physiopathological, genetic, molecular, and immunological mechanisms underlying the development of human renal cancers from the induction of precancerous lesions to the metastatic process. Our study aimed to review and discuss the characteristics of all the spontaneous animal models of renal carcinogenesis described in scientific literature to date and see how they could address future challenges in the field of personalized medicine. Methods and Materials We reviewed all the papers on PubMed which focus on spontaneous animal models of renal carcinogenesis. To do so, we used the keywords "spontaneous" AND "animal model" AND "renal cancer" in the PubMed search engine. We also conducted a search using the keywords "spontaneous" AND "animal model" AND "kidney cancer." PRISMA recommendations were used for the literature review. Results A total of 213 publications were found on PubMed with the keywords "spontaneous" AND "animal model" AND "kidney cancer." 219 publications were found on PubMed with the keywords "spontaneous" AND "animal model" AND "renal cancer." After pooling these 2 searches and removing the duplicate publications, 233 publications remained. Among these, 220 full-text articles were assessed for eligibility; 160 were removed because they were irrelevant to our topic, and the remaining 60 studies were included in our qualitative synthesis. Conclusions Many spontaneous animal models have been developed to study renal cancer. So far, these models have enabled the understanding of pathophysiological mechanisms underlying renal cancer. Though less appropriate than patient xenografts from the perspective of personalized medicine, we believe animal models can help medical professionals better understand the hows and whys of the genetic events underlying the intratumoral heterogeneity and spatial distribution of metastatic subclones., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Small-cell variant of RO is a rare subtype of renal tumor that can be easily misdiagnosed. To date, only 20 cases had been reported, with its genetic alterations largely unknown due to insufficient information., Materials and Methods: We report a case of the tumor with genetic characterization using exome sequencing chip. We also reviewed literature on this lesion to summarize clinicopathological presentation and differential diagnosis of the tumor., Discussion: Grossly, the tumor is yellow to grayish brown, with clear boundary, central scar, or cystic degeneration. Microscopically, small-cell variant RO show scant eosinophilic cytoplasm with small-round nuclei, arranged in small acini and tubules. Nucleoli and necrosis are rarely observed. Immunohistochemically, the tumor is positive for EMA, cytokeratin 18, CD117 and E-cadherin. Genetically, 4745 differentially expressed genes in this tumor, which encode tricarboxylic acid cycle enzymes and are involved in mitochondrial respiratory chain. This result strongly supports the diagnosis of small cell variant of RO. Findings from the molecular genetic analysis of our case suggests that metabolic pathway-related genes (PIK3R5, PI3KCB, PLA2G4E, PLA2G2A, PLA2G6, PLCB4, PLCG2) may be exploited as potential targets for diagnosis and treatment when necessary. These genes may provide new clues for future research., Conclusion: Small-cell variant of RO is considered benign renal neoplasms with good prognosis. A histochemical and immunohistochemical stains assist in diagnosis of this tumor. Definitive diagnosis can help avoid unnecessary total renal nephrectomy. The exact mechanism of Small-cell variant of RO remains to be further investigated., (Copyright © 2019. Published by Elsevier B.V.)

Previous studies have shown that alterations in the mechanical properties of cells may be associated with the onset and progression of some forms of pathology. In this paper, an experimental study of two types of cells, renal (cancer) and bladder (cancer) cells, is described which used acoustic radiation force (ARF) generated by a high-frequency ultrasound focusing transducer and performed on the operating platform of an inverted light microscope. Comparing images of cancer cells with those of normal cells of the same kind, we find that the cancer cells are more prone to deform than normal cells of the same kind under the same ARF. In addition, cancer cells with higher malignancy are more deformable than those with lower malignancy. This means that the deformability of cells may be used to distinguish diseased cells from normal ones, and more aggressive cells from less aggressive ones, which may provide a more rapid and accurate method for clinical diagnosis of urological disease in the future.

Nonfunctioning kidneys secondary to various etiologies display different histopathological features. Studies focused on incidence and types of renal neoplasms using the new World Health Organization and International Society of Urological Pathology classification system in various types of nonfunctioning kidneys are very limited. We identified 311 nephrectomies of nonfunctioning kidneys and categorized them into 5 categories: acquired cystic kidney disease (ACKD, n = 61); end-stage renal disease, nonspecific (ESRD, n = 63); adult polycystic kidney disease (APKD, n = 49); failed transplant kidney (FTK, n = 96); and those caused by obstructive conditions in the kidney (OCK, n = 42). ACKD (70%) and ESRD (43%) had higher cancer incidences than the other 3 groups (APKD = 2%, FTK = 0%, and OCK = 5%). Besides clear cell renal cell carcinoma (RCC) and papillary RCC, clear cell papillary RCC had a much higher incidence within ACKD patients (13/61) compared to other groups. ACKD-associated RCC was only identified in ACKD patients. ACKD patients had significantly longer dialysis duration compared to ESRD, APKD, and FTK. Although they had similar risk for clear cell RCC and papillary RCC, ACKD patients had a much higher risk for ACKD-associated RCC and clear cell papillary RCC than ESRD patients. Although most RCCs arising in these nonfunctioning kidneys were early pT1 stage, 6 ACKD patients and 3 ESRD patients had higher-stage diseases, which can be fatal if not treated appropriately. Therefore, precise clinicopathological classification of these nonfunctioning kidneys is important for predicting kidney cancer risk. These results indicate the need for active monitoring of the patients with high-risk nonfunctioning kidney diseases and appropriate surgical treatment when necessary., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Renal tumor scoring systems, such as the contact surface area value, aim to assist in predicting outcomes following robotic-assisted partial nephrectomy. The aim of this study is to identify associations between specific postoperative outcomes and the contact surface area of renal masses., Methods: We analyzed 332 consecutive robotic-assisted partial nephrectomies and calculated contact surface area for renal tumors with the contact surface area formula (CSA = 2πrd), where π ≈ 3.14, r = greatest tumor radius (cm), and d = greatest tumor depth (cm)., Results: Higher contact surface area was associated with longer warm ischemia time (P < .001), higher estimated blood loss (P < .001), and longer length of hospital stay (LOS) (P < .001). Higher contact surface area was significantly associated with decreased renal function at 1 day, 1 month, and 6 months following robotic-assisted partial nephrectomy., Conclusions: Contact surface area is associated with certain outcomes following robotic-assisted partial nephrectomy and may be a useful predictive tool., (© 2019 John Wiley & Sons, Ltd.)

Thymoquinone (TQ) is a monoterpene isolated from the oil of Nigella sativa seeds. The aim of this work was to evaluate the cytotoxic effects induced by TQ and its impact on the migration and invasion potential of 786-O human renal cancer cells. These cells were exposed to TQ (1-100 μM) for 24 and 48 h and cell viability assessed using the Crystal Violet and MTS assays. TQ treatment clearly decreased cell viability in a concentration- and time-dependent manner. TQ exposure moderately increased intracellular ROS levels and co-incubation with reduced glutathione markedly increased cell viability. Moreover, the effect of TQ in the cell cycle distribution was evaluated using flow cytometry, and an increase in the sub-G1 population was observed, especially at 30 μM, along with an increase in the % of apoptotic cells. TQ did not show genotoxic effects at a non-cytotoxic concentration (1.0 μM). At this concentration level, TQ significantly decreased the collective migration of 786-O cells, whereas it had no effect in chemotactic migration. TQ also decreased the invasiveness potential of 786-O cells, as evaluated by the transwell invasion assay. Overall, these results suggest that TQ presents an anticancer potential in the context of renal cancer, warranting further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: To explore the influencing factors of perioperative renal function change and their relationship with prognosis on renal cell carcinoma (RCC) patients with tumor thrombus after nephrectomy and thrombectomy., Methods: The clinical and pathological data of 135 patients with RCC and tumor thrombus, who underwent nephrectomy and thrombectomy at Peking University Third Hospital from May 2015 to July 2018, was retrospectively analyzed. Absolute change in estimated glomerular filtration rate (eGFR) (ACE) and percent change in eGFR (PCE) were calculated by preoperative and postoperative renal function. Linear regression analysis was used to explore the influencing factors of ACE and PCE, and logistic regression analysis was used to explore the influencing factors of worse postoperative renal function [eGFR≤60 mL/(min × 1.73 m^2)]. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method and multivariate Cox regression, which were used to explore the effect of ACE and PCE on prognosis., Results: Of all the 135 patients, 101 patients (74.8%) were male and 34 patients (25.2%) were female. The mean preoperative eGFR was 73.9 ± 21.8 mL/(min × 1.73 m^2) and postoperative eGFR was 69.5 ± 25.2 mL/(min × 1.73 m^2). In multivariate linear regression analysis, preoperative eGFR (P < 0.001) and pathological type (P = 0.038) were significant predictive factors of ACE. In aspect of PCE, preoperative eGFR (P < 0.001) and pathological type (P = 0.002) were significant predictors. In multivariate logistic regression analysis, preoperative eGFR (P = 0.016) was the only risk factor of predicting worse postoperative renal function. During follow-up, 22 patients (16.3%) were dead due to RCC. According to ROC analysis, the cut off value of ACE and PCE was 13.9 and 0.16, respectively. ACE> 13.9 and PCE > 0.16 indicated worse CSS (P = 0.006 and P = 0.047, respectively). However, in multivariate Cox regression analysis of several related factors, perinephric tissues invasion (P = 0.001), sarcomatoid differentiation (P = 0.001) and ACE> 13.9 (P = 0.002) were significant prognostic factors for CSS. PCE > 0.16 seemed to be not (P = 0.055)., Conclusion: We explored several clinicopathological risk factors of predicting renal function change and their relationship with prognosis of RCC patients with tumor thrombus after nephrectomy and thrombectomy. The renal function change, which was associated with preoperative eGFR and pathological type, was prognostic risk factor for CSS and ACE> 13.9 indicated the worse prognosis.

Purpose: Partial nephrectomy has been persuaded as a widely accepted surgical procedure for T1a (≤ 4 cm) renal tumors. However, when treating T1b (4-7 cm) renal cell carcinoma (RCC), the "optimal" method of surgery is still debatable. The aim of the research is to evaluate the long-term oncological and renal functional outcomes of laparoscopic radical nephrectomy (LRN) versus laparoscopic partial nephrectomy (LPN) for patients with T1b RCC., Materials and Methods: From March 1, 2003 to July 1, 2016, 331 patients were included in the current study. Patients presented with unilateral T1b RCC and underwent either LPN (n = 177) or LRN (n = 154). Relevant clinical data including follow-ups were acquired from patients., Results: The operation time of the LPN group patients was longer than that of LRN group (94.3 min vs 88.3 min, p = 0.021) and LPN group patients required shorter stays in hospital (11.5 days vs. 13.4 days, p = 0.009). Contrast to LRN, level of eGFR was superior in LPN at the postoperative time of 1 day, 3 months, 6 months, 12 months and 24 months (all p < 0.001). Kaplan-Meier plots and log-rank tests showed that patients undergoing LPN had a much higher overall survival (OS) (p = 0.007), cancer-specific survival (CSS) (p = 0.006) and metastasis-free survival (MFS) (p = 0.008) than those receiving LRN. In comparison with the LRN group, multivariable Cox analysis indicated that patients of the LPN group had a 1.9-fold OS, 2.9-fold CSS and 2.3-fold MFS., Conclusions: For patients with T1b RCC, our findings revealed that OS, CSS and MFS are superior in patients receiving LPN than those treated with LRN. With the benefit of preserving renal function of LPN, which leads a less incidence risk of other systematic diseases, LPN may be the preferred option when condition permits for cases involving T1b RCC.

Background/objective: Clear cell renal cell carcinoma (ccRCC) is characterized by a high degree of functional intratumoral heterogeneity (ITH). This is highlighted by the finding that tumor cell proliferation and intracellular signaling occur preferentially in the tumor periphery. The driving forces for such a spatial organization are largely unknown. Herein, we investigate the role of the tumor microenvironment in the control of tumor cell proliferation and functional ITH., Methods: Conditioned media (CM) derived from nonmalignant peritumoral kidney tissue were used to stimulate RCC cells in vitro. A neutralization assay was used to characterize the role of FGF-2 in the CM. The molecular mechanisms underlying the action of CM on RCC cells were investigated using immunoblotting, flow cytometry and immunofluorescence microscopy. Lastly, a series of ccRCCs were stained for Ki-67 and p27Kip1, and expression was analyzed in both tumor periphery and center., Results: We show that CM derived from nonmalignant kidney cells adjacent to an RCC can downregulate the expression of the CDK inhibitor p27Kip1 through enhanced protein degradation in an FGF-2-dependent fashion. FGF-2 functions mainly through the PI3K/AKT pathway downstream of its receptors, and RCC cells with constitutively high AKT activity show not only an enhanced degradation of p27Kip1 through the Emi1-Skp2 axis, but also a subcellular mislocalization of p27Kip1 to the cytoplasmic compartment. Such a mislocalization was also detected in the tumor periphery in vivo suggesting that p27Kip1 plays an important role in shaping this spatial niche., Conclusions: Our results suggest that the tumor microenvironment is involved in shaping the tumor peripheral niche by stimulating the enhanced proliferation that is characteristic for this zone., (The Author(s). Published by S. Karger AG, Basel.)

Background: The kidneys are vital organs acting as the body's filters that eliminate drugs and other waste products from the body. For effective cancer therapy, a delicate balance is required in the drug treatment and its elimination, which is critical for drug accumulation, toxicity, and kidney malfunction. However, how renal cell carcinoma (RCC) affects the kidneys in safely eliminating the byproducts of drug treatments in patients with severely dysregulated kidney functions had remained elusive. Recent advancements in dose adjustment have added to our understanding regarding how drug treatments could be effectively regulated in aberrant kidney cells, driving safe elimination and reducing drug accumulation and toxicity at the right time and space. Dose adjustment is the only standard systemic way applicable; however, it presents certain limitations. There is significant room for developing new strategies and alternatives to improve it., Objectives: Our analysis of the available treatments in literature discusses the treatment and their safe eliminations. In this study, we give an overview of the measures that could be taken to maintain the elimination gradient of anti-cancer drugs and restore normal kidney function in RCC. Differential therapeutics of RCC/mRCC in various clinical phase trials and the interaction of targeted therapeutics in response to vascular endothelial growth factor (VEGF) were also discussed., Conclusion: Such information might suggest a new direction in controlling treatment with safe elimination through dose adjustment and its associated alternatives in a judicious manner. A strategy to systematically focus on the safe elimination of anti-cancer drugs in RCC strongly needs advocating., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: We aimed to compare frailty status between patients with head and neck cancer (HNC) and other solid malignancies., Methods: Data collection was prospective, and the following were compared between cohorts at baseline: patient and tumour characteristics, Charlson Comorbidity Index (CCI), Groningen Frailty Indicator (GFI), Mini Mental State Examination (MMSE), Activities of Daily Living (ADLs), Instrumental ADLs (IADLs), Timed Up and Go (TUG) and Quality of Life (QoL). Univariate and multivariate logistic regression analyses were performed, and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were estimated., Results: In total, 242 patients with HNC and 180 with other oncology diagnoses were enrolled, of whom 32.6% and 21.8% were frail according to the GFI respectively. Comorbidity scores were not significantly different between the cohorts (7.4% vs. 13.1%; OR 0.54; 95% CI 0.28-1.02). In the univariate analysis, the GFI was significantly worse in the HNC cohort (OR 1.74; 95% CI 1.11-2.71). However, in the multivariate analysis, the MMSE, TUG and global QoL were significantly worse in the HNC cohort, with ORs of 20.03 (95% CI 2.44-164.31), 11.56 (95% CI 1.86-71.68) and 0.98 (95% CI 0.97-1.00) respectively., Conclusion: Patients with HNC appear to be frailer than patients with other solid malignancies despite comparable levels of comorbidity., (© 2019 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)