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1.
J Clin Lab Anal ; 36(6): e24442, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35441392

RESUMO

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.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/fisiologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/fisiopatologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Renais/genética , Neoplasias Renais/fisiopatologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/fisiologia
2.
Urology ; 159: 139-145, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606882

RESUMO

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.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Rim , Invasividade Neoplásica , Nefrectomia , Tecido Parenquimatoso , Cuidados Pré-Operatórios , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Testes de Função Renal/métodos , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Tamanho do Órgão , Tecido Parenquimatoso/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Prognóstico , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Tomografia Computadorizada por Raios X/métodos , Carga Tumoral
3.
Front Immunol ; 12: 778746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917092

RESUMO

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.


Assuntos
Carcinoma de Células Renais/diagnóstico , Infecções por HIV/complicações , Neoplasias Renais/diagnóstico , Avaliação Nutricional , Estado Nutricional , Adulto , Idoso , Pequim , Biomarcadores/sangue , Contagem de Linfócito CD4 , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Colesterol/sangue , Intervalo Livre de Doença , Feminino , Infecções por HIV/diagnóstico , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Nefrectomia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Albumina Sérica Humana/análise , Fatores de Tempo , Carga Viral
4.
Sci Rep ; 11(1): 19594, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599227

RESUMO

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.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Vesículas Extracelulares/química , Hipóxia/fisiopatologia , Neoplasias Renais/fisiopatologia , Proteoma , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Análise Espectral Raman/métodos
5.
Eur J Cancer ; 157: 50-58, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34482189

RESUMO

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 m2 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.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Carcinoma de Células Renais/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/fisiopatologia , Feminino , Humanos , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/fisiopatologia
6.
Oncol Rep ; 46(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34368882

RESUMO

The aim of the present study was to explore the effect of chaperon­mediated autophagy (CMA) through pyruvate kinase isoform M2 (PKM2) on the development of renal carcinoma (RCC) and its possible mechanisms. Lysosome­associated membrane protein 2A (LAMP­2A) and PKM2 expression levels were detected by collecting tissue samples from RCC patients. RNA interference was used to silence the LAMP­2A 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. Co­immunoprecipitation was used to detect the interaction between PKM2 and heat shock cognate 70 (HSC70). The results revealed that LAMP­2A and PKM2 expression levels were significantly increased in RCC tissues and cell lines (P<0.01). LAMP­2A silencing increased the expression level of PKM2 in A498 and 786­O cells. LAMP­2A and PKM2 silencing suppressed the proliferation and invasion and induced the apoptosis of A498 cells, and also affected the expression levels of related genes. Co­immunoprecipitation 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.


Assuntos
Apoptose/fisiologia , Carcinoma de Células Renais/fisiopatologia , Proteínas de Transporte/metabolismo , Proliferação de Células/fisiologia , Autofagia Mediada por Chaperonas/fisiologia , Neoplasias Renais/fisiopatologia , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Ligação a Hormônio da Tireoide
8.
Urology ; 157: 174-180, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34331997

RESUMO

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.


Assuntos
Neoplasias Renais/cirurgia , Rim/patologia , Nefrectomia/métodos , Idoso , Tomada de Decisão Clínica , Feminino , Glomerulosclerose Segmentar e Focal , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida
9.
Urol Oncol ; 39(11): 790.e17-790.e23, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34301458

RESUMO

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.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Neoplasias Renais/fisiopatologia , Linfonodos/patologia , Linfadenopatia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Exp Oncol ; 43(2): 185-188, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34190518

RESUMO

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.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Neoplasias Renais/fisiopatologia , Modelos Teóricos , Idoso , Feminino , Humanos , Neoplasias Renais/complicações , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologia
11.
BJU Int ; 128(6): 722-727, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34046981

RESUMO

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.


Assuntos
Adenoma Oxífilo/patologia , Adenoma Oxífilo/fisiopatologia , Taxa de Filtração Glomerular , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Carga Tumoral , Conduta Expectante , Adenoma Oxífilo/complicações , Adenoma Oxífilo/terapia , Idoso , Idoso de 80 Anos ou mais , Criocirurgia , Feminino , Seguimentos , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Taxa de Sobrevida
12.
Curr Urol Rep ; 22(7): 36, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34031793

RESUMO

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.


Assuntos
Taxa de Filtração Glomerular , Procedimentos Cirúrgicos Minimamente Invasivos , Nefrectomia , Cuidados Pós-Operatórios , Idoso , Estudos de Coortes , Feminino , Humanos , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Resultado do Tratamento
13.
J Cell Mol Med ; 25(7): 3610-3621, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33728749

RESUMO

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.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/fisiopatologia , gama-Glutamilciclotransferase/fisiologia , Biomarcadores Tumorais/genética , Carcinogênese/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/imunologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação para Baixo , Ferroptose , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/imunologia , Análise Multivariada , Nomogramas , Prognóstico , Fatores de Risco , Análise de Sobrevida , Regulação para Cima , gama-Glutamilciclotransferase/farmacologia
14.
Urol Int ; 105(5-6): 507-513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33626549

RESUMO

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.


Assuntos
Carcinoma de Células de Transição/diagnóstico por imagem , Carcinoma de Células de Transição/cirurgia , Imagem de Difusão por Ressonância Magnética , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Rim/fisiologia , Nefroureterectomia , Neoplasias Ureterais/diagnóstico por imagem , Neoplasias Ureterais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Volume Sanguíneo , Carcinoma de Células de Transição/fisiopatologia , Feminino , Humanos , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefroureterectomia/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Ureterais/fisiopatologia
15.
World J Urol ; 39(8): 2969-2975, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33416974

RESUMO

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.


Assuntos
Doenças do Sistema Nervoso Central , Oftalmopatias , Neoplasias Renais , Nefrectomia , Pancreatopatias , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/patologia , Progressão da Doença , Europa (Continente)/epidemiologia , Oftalmopatias/epidemiologia , Oftalmopatias/patologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/etiologia , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Masculino , Mutação , Gradação de Tumores , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Nefrectomia/estatística & dados numéricos , Pancreatopatias/epidemiologia , Pancreatopatias/patologia , Feocromocitoma/epidemiologia , Feocromocitoma/patologia , Período Pós-Operatório , Análise de Sobrevida , Carga Tumoral , Doença de von Hippel-Lindau/epidemiologia , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/patologia
16.
Clin Epigenetics ; 13(1): 12, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461589

RESUMO

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).


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/fisiopatologia , Metilação de DNA , Neoplasias Renais/genética , Neoplasias Renais/fisiopatologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
17.
J Robot Surg ; 15(1): 99-104, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32358741

RESUMO

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 m2. 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.


Assuntos
Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Peritônio/cirurgia , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Taxa de Filtração Glomerular , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Tempo de Internação , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
18.
Eur J Surg Oncol ; 47(2): 470-476, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32631709

RESUMO

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 m2) 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 m2 in Group A and 52.6 mL/min/1.73 m2 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.


Assuntos
Carcinoma de Células Renais/cirurgia , Taxa de Filtração Glomerular/fisiologia , Neoplasias Renais/cirurgia , Estadiamento de Neoplasias , Nefrectomia/mortalidade , Pontuação de Propensão , Insuficiência Renal Crônica/complicações , Isquemia Quente/métodos , Idoso , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/fisiopatologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências
19.
Clin Exp Nephrol ; 25(3): 315-321, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33125629

RESUMO

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.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Rim/cirurgia , Nefrectomia/efeitos adversos , Insuficiência Renal Crônica/etiologia , Tomografia Computadorizada por Raios X , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Rim/fisiopatologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
20.
J Urol ; 205(5): 1310-1320, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33356481

RESUMO

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 (R2) 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 m2) 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 m2 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.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Taxa de Filtração Glomerular , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Rim/fisiologia , Nefrectomia/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Período Pós-Operatório , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
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