Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.634
Filtrar
1.
J Environ Pathol Toxicol Oncol ; 40(2): 89-98, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822520

RESUMO

AIM: In our study, a new grading model (e-GM) including nuclear membrane irregularity highlighted by emerin expression was proposed for renal cell carcinomas (RCC). It was aimed to investigate the relationship of this model with WHO/ISUP grading system, histopathological features, and prognosis. METHODS AND RESULTS: 86 RCC cases were included in the study. The mean age of the patients was 59.65, and the mean tumor size was 6.36 cm. According to pTNM staging, 45 of the cases were stage 1, 11 were stage 2, 26 were stage 3, and 4 were stage 4. According to e-GM grading, advanced tumor grade was found to be associated with perirenal tissue extension, necrosis, lymphovascular invasion, distant metastasis, advanced pT and TNM stage. Nuclear membrane irregularity caused an increase in tumor grade in 17 wi-GS grade 1 cases, 14 WHO/ISUP grading system (wi-GS) grade 2 cases, and 1 wi-GS grade 3 case. In the stepwise statistical analysis, it was determined that the most important prognostic factor was the TNM stage, followed by age and tumor size. CONCLUSIONS: Statistical analyses showed that nuclear membrane irregularity should be a criterion for classification according to e-GM in wi-grade 2 cases, but not necessarily in wi-grade 1 cases. Nuclear membrane irregularity was a prominent feature at high tumor grades, and its expression in RCCs suggests that it may be a target for tumor-specific treatments.


Assuntos
Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Proteínas de Membrana/metabolismo , Proteínas Nucleares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Análise de Sobrevida , Carga Tumoral , Organização Mundial da Saúde
2.
Bull Cancer ; 108(3): 242-249, 2021 Mar.
Artigo em Francês | MEDLINE | ID: mdl-33648719

RESUMO

INTRODUCTION: To promote the early diagnosis of pediatric cancers in Ivory Coast, we have initiated a program to train local physicians in the warning signs and to raise public awareness. The aim of this work was to compare the times, stages and survival of patients before and three years after the initiation of the program. METHODS: This retrospective study involved children 0-17 years of age admitted from January to December 2014 and from May 2018 to April 2019. The Mann-Whitney non-parametric test and the Fisher's exact test were used to compare time limits, stages and survival. RESULTS: One hundred and fifty-nine doctors were trained and 1020 people were sensitized. The median age of the 216 children included was 7 years, sex ratio 1.4. For both periods, the median consultation times were 75 and 30 days (P=0.003) and the median diagnostic times were 120 and 105 days (P=0.033). High-risk lymphomas accounted for 60.5% and 58.5% (P=0.99) respectively and nephroblastoma 46.1% and 56.2% (P=0.51). The overall survival was 31% and 30.2% (P=0.92). DISCUSSION: The early diagnosis program had no impact. The diagnosis times and the proportion of cancer classified as high risk are comparable to the data reported in sub-Saharan Africa, which vary respectively from 7 to 15.8 weeks and from 60 to 71%. This program must be intensified, extended to all health workers and include improving access to care.


Assuntos
Detecção Precoce de Câncer , Educação Médica , Neoplasias/diagnóstico , Desenvolvimento de Programas , Avaliação de Sintomas/métodos , Adolescente , Criança , Pré-Escolar , Costa do Marfim , Diagnóstico Tardio , Feminino , Humanos , Lactente , Recém-Nascido , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Linfoma/diagnóstico , Linfoma/mortalidade , Masculino , Neoplasias/mortalidade , Neoplasias/patologia , Médicos , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Tumor de Wilms/diagnóstico , Tumor de Wilms/mortalidade
3.
N Engl J Med ; 384(9): 829-841, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33657295

RESUMO

BACKGROUND: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. METHODS: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point. RESULTS: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib. CONCLUSIONS: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).


Assuntos
Anilidas/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/administração & dosagem , Piridinas/administração & dosagem , Sunitinibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Análise de Intenção de Tratamento , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Piridinas/efeitos adversos , Qualidade de Vida , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Sunitinibe/efeitos adversos , Análise de Sobrevida
4.
Anticancer Res ; 41(3): 1539-1545, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788747

RESUMO

BACKGROUND/AIM: Nivolumab monotherapy for advanced/metastatic renal cell carcinoma (RCC) shows a survival benefit. The purpose of this study was to evaluate tumor responses to nivolumab in various metastatic and primary sites in patients with RCC. PATIENTS AND METHODS: We retrospectively reviewed 68 patients who underwent nivolumab monotherapy after one or more regimens of targeted therapy for advanced/metastatic RCC. The site-specific response was evaluated and progression-free survival was estimated. RESULTS: The site-specific overall response rates (ORRs) were as follows: lung (36%), bone (5%), lymph node (33%), liver (50%), adrenal gland (29%), pancreas (33%), and brain (0%). The ORR of bone metastasis was significantly worse in comparison to lung and liver metastases (p=0.017, 0.008). The site-specific median progression-free survival times were as follows: lung (5.1 months), bone (not reached), lymph node (not reached), and liver (17.5 months). CONCLUSION: Responses to nivolumab may vary depending on metastasized organs.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Carga Tumoral
5.
Medicine (Baltimore) ; 100(11): e24949, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725966

RESUMO

ABSTRACT: Currently, no effective prognostic model of clear cell renal cell carcinoma (ccRCC) based on immune cell infiltration has been developed. Recent studies have identified 6 immune groups (IS) in 33 solid tumors. We aimed to characterize the expression pattern of IS in ccRCC and evaluate the potential in predicting patient prognosis. The clinical information, immune subgroup, somatic mutation, copy number variation, and methylation score of patients with TCGA ccRCC cohort were downloaded from UCSC Xena for further analysis. The most dominant IS in ccRCC was the inflammatory subgroup (immune C3) (86.5%), regardless of different pathological stages, pathological grades, and genders. In the C3 subgroup, stage IV (69.1%) and grade 4 (69.9%) were the least presented. Survival analysis showed that the IS could effectively predict the overall survival (OS) (P < .0001) and disease-specific survival (DSS) (P < .0001) of ccRCC alone, of which group C3 (OS, HR = 2.3, P < .001; DSS, HR = 2.84, P < .001) exhibited the best prognosis. Among the most frequently mutated ccRCC genes, only VHL and PBRM1 were found to be common in the C3 group. The homologous recombination deficiency score was also lower. High heterogeneity was observed in immune cells and immunoregulatory genes of IS. Notably, CD4+ memory resting T cells were highly infiltrating, regulatory T cells (Treg) showed low infiltration, and most immunoregulatory genes (such as CX3CL1, IFNA2, TLR4, SELP, HMGB1, and TNFRSF14) were highly expressed in the C3 subgroup than in other subgroups. Enrichment analysis showed that adipogenesis, apical junction, hypoxia, IL2 STAT5 signaling, TGF-beta signaling, and UV response DN were activated, whereas E2F targets, G2M checkpoint, and MYC targets V2 were downregulated in the C3 group. Immune classification can more accurately classify ccRCC patients and predict OS and DSS. Thus, IS-based classification may be a valuable tool that enables individualized treatment of patients with ccRCC.


Assuntos
Carcinoma de Células Renais/classificação , Imunofenotipagem/métodos , Neoplasias Renais/classificação , Subpopulações de Linfócitos/imunologia , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Quimiocina CX3CL1 , Variações do Número de Cópias de DNA/imunologia , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica/imunologia , Proteína HMGB1 , Humanos , Interferon-alfa , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Metilação , Mutação/imunologia , Gradação de Tumores , Estadiamento de Neoplasias , Selectina-P , Valor Preditivo dos Testes , Prognóstico , Membro 14 de Receptores do Fator de Necrose Tumoral , Transdução de Sinais/imunologia , Análise de Sobrevida , Receptor 4 Toll-Like , Fatores de Transcrição , Proteína Supressora de Tumor Von Hippel-Lindau
6.
Medicine (Baltimore) ; 100(10): e25127, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725913

RESUMO

ABSTRACT: Prognostic nutritional index (PNI) could reflect the nutrition and inflammation status in cancer patients. This study aims to identify the prognostic significance of PNI in patients with renal cell carcinoma (RCC).A total of 694 RCC patients from our institution were included in this study. The prognostic correlation between PNI and overall survival (OS) and recurrence-free survival (RFS) was analyzed respectively using Kaplan-Meier method and univariate and multivariate Cox model. Studies about the association between pretreatment or preoperative PNI and prognosis of RCC were systemically reviewed and a meta-analysis method was performed to further evaluate the pooled prognostic value of PNI in RCC.267 (38.47%) RCC patients had low PNI according to the cut off value (49.08). Low PNI was associated with poor OS (P < .001) and RFS (P < .001), respectively. In the multivariate Cox analysis, PNI was identified to be an independent prognostic factor for OS (hazard ratio [HR] = 2.13, 95%CI: 1.25-3.62, P = .005). Compared to other nutritional indexes, this risk correlation of PNI is better than that of geriatric nutritional risk index (GNRI; HR = 1.19; P = .531), while is no better than that of neutrophil-lymphocyte ratio (NLR; 1/HR = 2.56; P < .001) and platelet-lymphocyte ratio (PLR; 1/HR = 2.85; P < .001) respectively. Meanwhile, additional 4785 patients from 6 studies were included into pooled analysis. For RCC patients who underwent surgery, low preoperative PNI was significantly associated with worse OS (pooled HR = 1.57, 95%CI: 1.37-1.80, P < .001) and worse RFS (pooled HR = 1.69, 95%CI: 1.45-1.96, P < .001). Furthermore, low PNI (<41-51) was also significantly associated with poor OS (HR = 1.78, 95%CI: 1.26-2.53 P < .05) and poor RFS (HR = 2.03, 95%CI: 1.40-2.95, P < .05) in advanced cases treated with targeted therapies.The present evidences show that PNI is an independent prognostic factor in RCC. Low PNI is significant associated with poor prognosis of RCC patients.


Assuntos
Carcinoma de Células Renais/mortalidade , Inflamação/diagnóstico , Neoplasias Renais/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Avaliação Nutricional , Adulto , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Inflamação/imunologia , Neoplasias Renais/complicações , Neoplasias Renais/imunologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Nefrectomia , Estado Nutricional/imunologia , Período Pré-Operatório , Prognóstico , Valores de Referência , Estudos Retrospectivos , Medição de Risco/métodos , Adulto Jovem
7.
Am J Clin Oncol ; 44(3): 121-125, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33617179

RESUMO

OBJECTIVES: The aim of our study was to collect data about of the outcome of metastatic renal cell carcinoma patients who progressed after immune checkpoint inhibitors in order to enhance data about efficacy and safety of treatment beyond immune-oncology (IO). MATERIALS AND METHODS: A total of 162 eligible patients, progressing to IO, were enrolled from 16 Italian referral centers adhering to the Meet-Uro association. Baseline characteristics, outcome data and toxicities were retrospectively collected. Descriptive analysis was made using median values and ranges. Kaplan-Meier method and Mantel-Haenszel log-rank test were performed to compare differences between groups. RESULTS: A total of 111 patients (68.5%) were treated after IO progression. In all, 51 patients (31.5%) did not receive further treatment for clinical deterioration. Median IO progression free survival (PFS) was 4 months (95% confidence interval [CI]: 3.1-4.8). IO-PFS tends to be longer in patients reporting adverse events (AE) of any grade (5.03 [95% CI: 3.8-6.1] vs. 2.99 [95% CI: 2.4-3.5] months P=0.004). Subsequent therapies included cabozantinib (n=79, 48%), everolimus (n=11, 6.7%), and others (n=21, 12.9%).Median PFS post-IO was 6.5 months (95% CI: 5.1-7.8). Cabozantinib showed longer PFS compared with everolimus (7.6 mo [95% CI: 5.2-10.1] vs. 3.2 mo [95% CI: 1.8-4.5]) (hazard ratio: 0.2; 95% CI: 0.1026-0.7968) and other drugs (4.3 mo [95% CI: 1.3-7.4]) (hazard ratio: 0.6; 95% CI: 0.35-1.23). All grade AE were reported in 83 patients (74%) and G3 to G4 AE in 39 patients (35%). Target therapies post-IO showed median overall survival of 14.7 months (95% CI: 0.3-21.4). CONCLUSIONS: In our real world experience after progression to IO, vascular endotelial groth factor-tyrosine kinase inhibitors, given to patients, proved to be active and safe choices. Cabozantinib was associated with a better outcome in terms of median PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Idoso , Anilidas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Progressão da Doença , Everolimo/administração & dosagem , Feminino , Humanos , Itália , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Piridinas/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
8.
Nat Commun ; 12(1): 808, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547292

RESUMO

Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/imunologia , Regulação Neoplásica da Expressão Gênica , /imunologia , Neoplasias Renais/imunologia , Tumor Rabdoide/imunologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Mutação , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/imunologia , Estudos Retrospectivos , Tumor Rabdoide/tratamento farmacológico , Tumor Rabdoide/genética , Tumor Rabdoide/mortalidade , Transdução de Sinais , Análise de Sobrevida , Transcrição Genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/imunologia , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/imunologia
9.
Medicine (Baltimore) ; 100(3): e24152, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546029

RESUMO

BACKGROUND: The prognostic value of pretreatment lymphocyte to monocyte ratio in patients with renal cell carcinoma and, especially, in non-metastatic patients remains controversial. METHODS: We conducted a PRISMA-compliant meta-analysis to systematically assess the prognostic value of LMR in patients with non-metastatic RCC. Overall survival, cancer-specific survival, and disease-free survival were analyzed. Pooled hazard ratios and 95% confidence intervals were calculated. RESULTS: Seven studies comprising 4666 patients were included in the analysis. Unlike those observed in a previous meta-analysis, a lower lymphocyte to monocyte ratio was associated with poorer cancer-specific survival (fix-effect model, hazard ratio 3.04, 95% confidence intervals 2.05-4.51, P < .05). Heterogeneity Chi-squared value Q exp = 0. (P = .82) (I2 = 0%). However, the association between a low lymphocyte to monocyte ratio and overall survival or disease-free survival did not obtain significance. CONCLUSION: A lower lymphocyte to monocyte ratio implied poor cancer-specific survival in patients with non-metastatic renal cell carcinoma. Prospective studies are required to confirm our findings. REGISTRATION NUMBER: ClinicalTrials.gov (identifier: NCT04213664).


Assuntos
Carcinoma de Células Renais/imunologia , Neoplasias Renais/imunologia , Carcinoma de Células Renais/mortalidade , Humanos , Neoplasias Renais/mortalidade , Contagem de Linfócitos , Metanálise como Assunto , Prognóstico , Revisões Sistemáticas como Assunto
10.
DNA Cell Biol ; 40(3): 532-542, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33625263

RESUMO

Renal cell carcinoma (RCC) is one of the most frequently occurring tumors worldwide. Herein, we established a microRNA (miRNA) predicting signature to assess the prognosis of papillary-type RCC (PRCC) patients. miR-1293, miR-34a, miR-551b, miR-937, miR-299, and miR-3199-2 were used in building the overall survival (OS)-related signature, whereas miR-7156, miR-211, and miR-301b were used to construct the formula of recurrence-free survival (RFS) with the help of LASSO Cox regression analysis. The Kaplan-Meier and receiver operating characteristic curves indicated good discrimination and efficiency of the two signatures. Functional annotation for the downstream genes of the OS/RFS-related miRNAs exposed the potential mechanisms of PRCC. Notably, the multivariate analyses suggested that the two signatures were independent risk factors for PRCC patients and had better prognostic capacity than any other classifier. In addition, the nomogram indicated synthesis effects and showed better predictive performance than clinicopathologic features and our signatures. We validated the OS and RFS prediction formulas in clinical samples and met our expectations. Finally, we established two novel miRNA-based OS and RFS predicting signatures for PRCC, which are reliable tools for assessing the prognosis of PRCC patients.


Assuntos
Carcinoma Papilar , Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , RNA Neoplásico , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/mortalidade , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Taxa de Sobrevida
11.
Medicine (Baltimore) ; 100(1): e24257, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429832

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) accounts for 2% to 3% of all human malignancies and is the 9th most common malignancy in Western countries. Due to the development of surgical procedures and the use of novel drugs, survival has been significantly prolonged. However, current challenges include how to diagnose RCC earlier and how to overcome drug resistance. Methods: We explored the relationship between the transcription level of IFI16 and clinical data in RCC through various online databases, including ONCOMINE, GEPIA, HPA, Timer and COEXPEDIA. RESULTS: In comparison with corresponding normal tissues, IFI16 mRNA expression levels were higher in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) tissues. In KIRC, the higher expression of IFI16 was associated with lower overall survival (P = .037). In KIRP, the higher expression IFI16 was associated with lower disease-free survival and overall survival (P = .037 and P = .011). In contrast, the IFI16 expression was negatively correlated with tumor purity in kidney chromophobe, KIRC and KIRP (all P < .05). In KIRC and KIRP, the expression of IFI16 was positively correlated with tumor-infiltrating immune cells (TIICs) (all P < .05), except macrophages in KIRP. In KIRC, the main TIICs were B cells, CD4+T cells, neutrophils, and dendritic cells, while the main TIICs in the high amplification state were macrophage (all P < .0001). Functional enrichment analysis by gene ontology and Kyoto Encyclopedia of Genes and Genomes highlighted enrichment of neutrophil degranulation, phagocytosis and vesicle-mediated transport regulation, and pathways including tuberculosis, toxoplasmosis, phagosome, leishmaniasis, and Fc gamma R-mediated. CONCLUSIONS: IFI16 is overexpressed in RCC and may be an important oncogene in the progression of kidney. In addition, IFI16 may a marker for RCC diagnosis and prognosis, which may be related to immune infiltration.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Biologia Computacional , Bases de Dados Factuais , Intervalo Livre de Doença , Humanos , Neoplasias Renais/metabolismo , Prognóstico
12.
Cancer Sci ; 112(3): 1038-1047, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33410234

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme associated with immunomodulation through its regulation of the tryptophan-kynurenine (Kyn) pathway in advanced cancers, including metastatic renal cell carcinoma (mRCC). However, the failure of IDO1 inhibitors when used in combination with immune checkpoint inhibitors (ICIs), as observed in clinical trials, raises a number of questions. This study aimed to investigate the association of tryptophan 2,3-dioxygenase (TDO) and IDO1 with cancer development and resistance to immunotherapy in patients with RCC. In our analysis of RCC tissue samples, tissue Kyn levels were elevated in advanced-stage RCC and correlated well with TDO expression levels in RCC tumor cells. In patients with mRCC, TDO rather than IDO1 was expressed in RCC tumor cells, showing a strong association with Kyn expression. Furthermore, immunohistochemical staining of TDO was strongly associated with the staining intensity of forkhead box P3, as well as ICI therapy response and survival in patients with mRCC. Our study is the first to show that TDO expression in tumor tissues is associated with progression and survival, confirming its potential as a predictive biomarker of primary resistance to immunotherapy in patients with mRCC. Our findings suggest that strategies aimed at inhibiting TDO, rather than IDO1, in combination with ICI therapy may aid in the control of mRCC progression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Rim/patologia , Triptofano Oxigenase/metabolismo , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , /uso terapêutico , Imuno-Histoquímica , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Rim/cirurgia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Cinurenina/análise , Cinurenina/metabolismo , Masculino , Pessoa de Meia-Idade , Nefrectomia , Intervalo Livre de Progressão , Triptofano/metabolismo , Triptofano Oxigenase/análise , Triptofano Oxigenase/antagonistas & inibidores
13.
JAMA Netw Open ; 4(1): e2021869, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33475752

RESUMO

Importance: There exists considerable biological and clinical variability between histologic variants of metastatic renal cell carcinoma (mRCC). Data reporting on patterns of metastasis in histologic variants of mRCC are sparse. Objective: To characterize sites of metastasis and their association with survival across the 3 most common histologic variants of mRCC: clear cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). Design, Setting, and Participants: In this multicenter, international cohort study, the International mRCC Database Consortium (IMDC) database was used to identify consecutive patients starting systemic therapy for mRCC between 2002 and 2019. Patients with mixed histologic subtype were excluded. Statistical analysis was performed from February to June 2020. Exposures: Data regarding histologic subtype and sites of metastatic involvement at the time of first systemic therapy initiation were collected. Main Outcomes and Measures: The primary outcomes were prevalence of metastatic site involvement and overall survival (OS) from time of systemic therapy initiation. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. Results: A total of 10 105 patients were eligible for analysis. Median (interquartile range) age at diagnosis was 60 (53-67) years, 7310 (72.4%) were men and 8526 (84.5%) underwent nephrectomy. Of these, 9252 (92%) had ccRCC, 667 (7%) had pRCC, and 186 (2%) had chrRCC. The median number of sites of metastasis was 2 (range, 0-7). In ccRCC, the most common sites of metastasis were lung (70%; 6189 of 8804 patients [448 missing]), lymph nodes (45%; 3874 of 8655 patients [597 missing]), bone (32%; 2847 of 8817 patients [435 missing]), liver (18%; 1560 of 8804 [448 missing]), and adrenal gland (10%; 678 of 6673 patients [2579 missing]). Sites of metastasis varied between subtypes. Lung, adrenal, brain, and pancreatic metastases were more frequent in ccRCC, lymph node involvement was more common in pRCC, and liver metastases were more frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (95% CI, 13.7-18.8 months) for the pleura and 50 months (95% CI, 41.1-55.5 months) for the pancreas. Compared with ccRCC, patients with pRCC tended to have lower OS, regardless of metastatic site. Conclusions and Relevance: Sites of metastatic involvement differ according to histologic subtype in mRCC and are associated with OS. These data highlight the clinical and biological variability between histologic subtypes of mRCC. Patterns of metastatic spread may reflect differences in underlying disease biology. Further work to investigate differences in immune, molecular, and genetic profiles between metastatic sites and histologic subtypes is encouraged.


Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Idoso , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/terapia , Estudos de Coortes , Feminino , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nefrectomia
14.
Biochem Biophys Res Commun ; 534: 157-164, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33308825

RESUMO

Renal clear cell carcinoma (ccRCC), is an inflammation-related malignancy with poor therapeutic outcome. Interferon-induced transmembrane protein 2 (IFITM2), an inflammation related gene, is reported to promote tumor progression via inducing cytokine release and lymphatic metastasis. However, IFITM2's role in ccRCC remains unclear. In this study, we aimed to explore the role of IFITM2 in ccRCC. In vitro studies displayed overexpressed IFITM2 level in tumor tissues, while analysis of 538 cases from TCGA unveiled the correlation of upregulated-IFITM2 with shorter survival. Migration and invasion of ccRCC were inhibited following the downregulation of IFITM2. Cocultured with IFITM2-silenced ccRCC cells, human lymphatic endothelial cells were inhibited in proliferation, migration and tube formation, indicating that lymphangiognesis was contributed by IFITM2 expression. Taken together, IFITM2 promotes ccRCC progression by inducing malignant characteristics and lymphatic metastasis. Therefore, IFITM2 represents a promising novel target for therapy and effective prediction of malignancy of ccRCC.


Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Proteínas de Membrana/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Renais/metabolismo , Linfangiogênese , Metástase Linfática , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Prognóstico
15.
J Vasc Interv Radiol ; 32(1): 33-38, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33308948

RESUMO

PURPOSE: To determine effect of body mass index (BMI) on safety and cancer-related outcomes of thermal ablation for renal cell carcinoma (RRC). MATERIALS AND METHODS: This retrospective study evaluated 427 patients (287 men and 140 women; mean [SD] age, 72 [12] y) who were treated with thermal ablation for RCC between October 2006 and December 2017. Patients were stratified by BMI into 3 categories: normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2). Of 427 patients, 71 (16%) were normal weight, 157 (37%) were overweight, and 199 (47%) were obese. Complication rates, local recurrence, and residual disease were compared in the 3 cohorts. RESULTS: No differences in technical success between normal-weight, overweight, and obese patients were identified (P = .72). Primary technique efficacy rates for normal-weight, overweight, and obese patients were 91%, 94%, and 93% (P = .71). There was no significant difference in RCC specific-free survival, disease-free survival, and metastasis-free survival between obese, overweight, and normal-weight groups (P = .72, P = .43, P = .99). Complication rates between the 3 cohorts were similar (normal weight 4%, overweight 2%, obese 3%; P = .71). CONCLUSIONS: CT-guided renal ablation is safe, feasible, and effective regardless of BMI.


Assuntos
Índice de Massa Corporal , Carcinoma de Células Renais/cirurgia , Criocirurgia , Neoplasias Renais/cirurgia , Micro-Ondas/uso terapêutico , Obesidade/diagnóstico , Ablação por Radiofrequência , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Criocirurgia/efeitos adversos , Criocirurgia/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Micro-Ondas/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Obesidade/mortalidade , Segurança do Paciente , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
16.
J Urol ; 205(1): 78-85, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32614274

RESUMO

PURPOSE: The time between radiographic identification of a renal tumor and surgery can be concerning for patients and clinicians due to fears of tumor progression while awaiting treatment. This study aimed to evaluate the association between surgical wait time and oncologic outcomes for patients with renal cell carcinoma. MATERIALS AND METHODS: The Canadian Kidney Cancer Information System is a multi-institutional prospective cohort initiated in January 2011. Patients with clinical stage T1b or greater renal cell carcinoma diagnosed between January 2011 and December 2019 were included in this analysis. Outcomes of interest were pathological up staging, cancer recurrence, cancer specific survival and overall survival. Time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models. RESULTS: A total of 1,769 patients satisfied the study criteria. Median wait times were 54 days (IQR 29-86) for the overall cohort and 81 days (IQR 49-127) for cT1b tumors (1,166 patients), 45 days (IQR 27-71) for cT2 tumors (672 cases) and 35 days (IQR 18-61) for cT3/4 tumors (563). Adjusting for comorbidity, tumor size, grade, histological subtype, margin status and pathological stage, there was no association between prolonged wait time and cancer recurrence or death. CONCLUSIONS: In the context of current surgeon triaging practices surgical wait times up to 24 weeks were not associated with adverse oncologic outcomes after 2 years of followup.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Nefrectomia/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Canadá/epidemiologia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Nefrectomia/normas , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Radiografia/estatística & dados numéricos , Fatores de Tempo , Tempo para o Tratamento/normas , Triagem/normas , Triagem/estatística & dados numéricos
17.
Cancer Sci ; 112(3): 1084-1094, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33368857

RESUMO

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.


Assuntos
Carcinoma de Células de Transição/mortalidade , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/mortalidade , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/terapia , Quimioterapia Adjuvante , Cistectomia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Músculo Liso/patologia , Músculo Liso/cirurgia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Nefroureterectomia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/terapia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/secundário , Neoplasias da Bexiga Urinária/terapia
18.
J Surg Oncol ; 123(2): 687-692, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33333591

RESUMO

BACKGROUND: Data about the impact of surgical margin positivity on patient outcomes following radical nephrectomy (RN) for renal cell carcinoma (RCC) is limited. We evaluate the effect of positive surgical margins (PSMs) on relapse-free survival (RFS) and overall survival (OS.) METHODS: Clinicopathologic data of patients who underwent RN for RCC was analyzed based on margin status. χ2 and Student t test were used to compare groups. Cox regression analysis was used for the analysis. Kaplan-Meier method was used for survival curves. RESULTS: A total of 485 patients who underwent RN for RCC were analyzed. Most patients with T1/T2 stage had NSM. Most patients with T4 had PSM. T3 patients were split between the two groups. Analysis of the T3 group showed shorter RFS in the PSM group at 3 years (hazard ratio [HR]: 4.3, p = .01), and 5 years (HR: 4.3, p = .01.) OS analysis showed worse OS in PSM but not statistically significant. There was a significant association between PSM and laterality (p = .023) and histologic type (p = .025.) CONCLUSIONS: PSM was associated with shorter RFS after RN in T3 RCC patients. There was a trend towards worse OS in the PSM group, but it did not reach statistical significance. Laterality and histologic type were associated with surgical margin status.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Margens de Excisão , Nefrectomia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Medicine (Baltimore) ; 99(52): e23465, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350729

RESUMO

ABSTRACT: Survival heterogeneity is observed among renal cell carcinoma (RCC) patients with metastases in different organs. Moreover, almost all previous prognostic nomograms based on data from metastatic RCC patients did not take competing events, such as death from cerebrovascular and heart diseases, into account. We aimed to construct novel prognostic nomograms for patients with lung metastatic clear cell RCC (LMCCRCC).Data of 712 non-Hispanic white LMCCRCC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Nomograms for predicting overall survival (OS) and disease-specific survival (DSS) were established using the Cox approach and Fine and Gray approach, respectively, and their performances were assessed using the concordance index (C-index), calibration plots, and an independent cohort comprising 181 Hispanic patients.Sex, tumor grade, T stage, N stage, presence or absence of bone metastases, and presence or absence of brain metastases were independent predictors for both OS and DSS. Additionally, presence or absence of liver metastases was an independent predictor only for DSS. Meanwhile, age at diagnosis was independently associated with OS. The C-indexes of the nomograms were 0.702 for OS and 0.723 for DSS in internal validation. In external validation, the C-indexes were 0.700 for OS and 0.708 for DSS. Both internal and external calibration plots showed excellent consistency between the prediction and the observation.The current study developed a novel nomogram for predicting individual OS in LMCCRCC patients. Moreover, we constructed an effective competing risk nomogram for predicting their individual DSS for the first time.


Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Zhonghua Zhong Liu Za Zhi ; 42(12): 1001-1006, 2020 Dec 23.
Artigo em Chinês | MEDLINE | ID: mdl-33342155

RESUMO

Objective: To estimate cancer incidence and mortality of kidney and unspecified urinary organs in China using cancer registry data in 2015. Methods: The cancer registry data from 501 local cancer registries in China were collected, checked and assessed based on the criteria of data quality control of the National Central Cancer Registry of China (NCCRC), and data from 368 registries were qualified for the analysis. Cancer incidence and mortality rates of kidney and unspecified urinary organs stratified by geographical location (eastern, middle, western areas), gender, age groups were calculated. Population data of 2015 was used to estimate the cancer cases and deaths of kidney and unspecified urinary organs in China. Chinese standard population in 2000 and Segi's world population were used for the calculation of age-standardized incidence and mortality rates. Results: A total of 74.2 thousand new cancer cases of kidney and unspecified urinary organs were diagnosed in 2015, 46.9 thousand of them were male, while 27.3 thousand were female, with a crude incidence rate of 5.40/10(5). The age-standardized incidence rates by Chinese (ASIRC) and world standard population (ASIRW) were 3.57/10(5) and 3.56/10(5), respectively. A total of 53.4 thousand and 20.8 thousand new cases were diagnosed in urban and rural area, with incidence rates of 6.93/10(5) and 3.45/10(5), respectively. The ASIRC of urban area was higher than that of rural area. There were 39.2 thousand, 20.6 thousand, and 14.4 thousand new cases diagnosed in eastern, middle, and western areas of China, respectively. The crude incidence rates were 7.60/10(5), 4.47/10(5), and 3.63/10(5), respectively, with a descend ASIRC of each area. A total of 27.1 thousand death cases reported, of them 16.9 thousand were male, while 10.2 thousand were female, with a crude mortality rate of 1.97/10(5), both of the ASIRC and ASMRW were 1.21/10(5). The deaths of urban and rural area were 19.5 thousand and 7.6 thousand cases, with the crude mortality rates of 2.53/10(5) and 1.26/10(5), respectively. The ASIRC of urban area was higher than that of rural area. There were 13.4 thousand, 8.4 thousand, and 5.1 thousand death cases reported in eastern, middle, and western areas, respectively, the crude mortality rates were 2.61/10(5), 1.83/10(5) and 1.30/10(5), respectively, with a descend ASIRC of each area. Conclusion: The disease burden of kidney cancer differs between urban area and rural area, and differs among eastern, middle, and western areas of China, therefore, different prevent and treatment strategies should be taken in different areas of China.


Assuntos
Neoplasias Renais , Neoplasias Urológicas , China/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Renais/epidemiologia , Neoplasias Renais/mortalidade , Masculino , Sistema de Registros , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/mortalidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...