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1.
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
2.
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
3.
Hinyokika Kiyo ; 67(2): 57-61, 2021 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-33657772

RESUMO

We evaluated the impact of tumor shrinkage (TS) induced by molecular targeted therapy as the first-line systemic therapy on the survival of patients with metastatic renal cell carcinoma (mRCC). A total of 67 patients with mRCC who received first-line molecular targeted therapy were included in this study. Sixty patients were evaluable by response evaluation criteria in solid tumors. Patients underwent the first evaluation at 8-12 weeks after the start of the therapy. Twenty patients had TS ≧30%, 32 from 30% to -20%, and 8 ≦-20%. The median overall survival periods of patients who achieved TS ≧30%, from 30% to -20%, and ≦-20% at first evaluation were 41.0, 35.0, and 11.5 months, respectively. Univariate and multivariate analyses showed that TS of≧0%, in addition to negative C-reactive protein and the absence of bone metastasis were good predictors of overall survival. The patients who achieved 0% or more at the initial evaluation had longer survival than those who had no tumor reduction (40.0 months vs 12.0 months, p<0. 001). These findings suggest that early TS affects overall survival in real practice. We should consider alternative therapies for patients who have not achieved tumor reduction at the initial evaluation.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Terapia de Alvo Molecular , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
4.
Hinyokika Kiyo ; 67(2): 63-66, 2021 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-33657773

RESUMO

A 67-year-old man underwent open radical left nephrectomy for left renal cell carcinoma [pT4N0M1 (right lower lobe of lung)] and thoracoscopic partial right lung resection for lung metastasis. The patient subsequently developed a solitary lung metastasis at 10 months and then at 26 months postoperatively. He underwent partial lung resection on each occasion. During the 28 months postoperatively, he was found to have a 12 mm middle mediastinal lymph node metastasis and a 30 mm splenic metastasis, which gradually increased in size. Three months after discovery, sunitinib was initiated at 37.5 mg 2 weeks on/1 week off. Twelve days later, the patient presented with complaints of fever. A gas-producing splenic abscess was diagnosed and he was admitted on the same day. His condition improved with antibiotics and splenic drainage. On day 35 of hospitalization, he underwent laparoscopic splenectomy. The patient's postoperative clinical course was uneventful and he was discharged 7 days after the surgery.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Esplenopatias , Neoplasias Esplênicas , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Abscesso/etiologia , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Masculino , Neoplasias Esplênicas/diagnóstico por imagem , Neoplasias Esplênicas/tratamento farmacológico , Neoplasias Esplênicas/cirurgia , Sunitinibe/uso terapêutico
5.
Medicine (Baltimore) ; 100(12): e24903, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761648

RESUMO

ABSTRACT: Papillary renal cell carcinoma (PRCC) is the second most common type of renal carcinoma following clear cell renal cell carcinoma, and the role of immune-related genes (IRGs) in tumorigenesis and metastasis is evident; its prognostic value in PRCC remains unclear. In this study, we downloaded the gene expression profiles and clinical data of patients with PRCC from The Cancer Genome Atlas (TCGA) database and obtained IRGs from the ImmPort database. A total of 371 differentially expressed IRGs (DEIRGs) were discovered between PRCC and normal kidney tissues. Prognostic DEIRGs (PDEIRGs) were identified by univariate Cox regression analysis. Then, we screened the four most representative PDEIRGs (IL13RA2, CCL19, BIRC5, and INHBE) and used them to construct a risk model to predict the prognosis of patients with PRCC. This model precisely stratified survival outcome and accurately identified mutation burden in PRCC. Thus, our results suggest that these four PDEIRGs are available prognostic predictors for PRCC. They could be used to assess the prognosis and to guide individualized treatments for patients with PRCC.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Medição de Risco/estatística & dados numéricos , Carcinoma de Células Renais/patologia , Quimiocina CCL19/genética , Humanos , Subunidades beta de Inibinas/genética , Subunidade alfa2 de Receptor de Interleucina-13/genética , Neoplasias Renais/patologia , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Survivina/genética , Transcriptoma , Carga Tumoral/genética
6.
Medicine (Baltimore) ; 100(10): e24910, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725849

RESUMO

RATIONALE: Ocular metastasis of renal cell carcinoma (RCC) is rare, and mainly located on the choroid. We report a choroidal metastasis from RCC, which was recorded by a smartphone with an interface eyepiece adapter mounted on a slit lamp. PATIENT CONCERNS: A 45-year-old female presented with 1-month history of painless occlusion of the vision field on the left eye, who had undergone right nephrectomy for RCC 19 months ago. DIAGNOSES: A smooth, hemispherical and brown protrusion was found behind the pupil nasally. An enhanced computed tomography scan of the orbit showed a slightly high-density hemispherical nodule involving the nasal portions of the left eyeball, the enhancement of the lesion was obvious and homogeneous. A metastatic choroidal space-occupying lesion from RCC was highly suspected according to the clinical and radiological findings. INTERVENTIONS: The patient was advised to undergo further treatment, such as radiotherapy. OUTCOMES: The images of choroid metastasis were recorded by the smartphone with the interface eyepiece adapter mounted on the slit lamp handily. CONCLUSIONS: The smartphone with an interface eyepiece adapter mounted on the slit lamp can be widely used to record the precious images in the clinic in a timely manner.


Assuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias da Coroide/diagnóstico , Plexo Corióideo/diagnóstico por imagem , Neoplasias Renais/patologia , Smartphone , Carcinoma de Células Renais/secundário , Neoplasias da Coroide/secundário , Feminino , Humanos , Neoplasias Renais/cirurgia , Pessoa de Meia-Idade , Nefrectomia , Lâmpada de Fenda , Microscopia com Lâmpada de Fenda/instrumentação , Tomografia Computadorizada por Raios X
7.
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
8.
Cancer Treat Rev ; 94: 102157, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33607461

RESUMO

A major breakthrough in cancer immunotherapy was the development of monoclonal antibodies targeting inhibitory immune checkpoint proteins. This approach demonstrated significant antitumor activity and efficacy in different cancer types, including metastatic renal cell carcinoma (mRCC). In the majority of patients, this drug is able to restore the patient's tumour-specific T-cell-mediated response thus improving both overall survival and objective response rate. However, a lack of clinical response occurs in a number of patients, raising questions about how to predict and increase the number of patients who receive long-term clinical benefit from immune checkpoint therapy or not. The aim of this review is to summarize available data about immune biomarkers in patients with mRCC treated with immunotherapy.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Animais , Antígeno B7-H1/biossíntese , Antígeno B7-H1/imunologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Transcriptoma , Ensaios Antitumorais Modelo de Xenoenxerto
9.
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
10.
J Surg Oncol ; 123(3): 739-750, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33595892

RESUMO

Immune checkpoint blockade (ICB) is the foundation of current first-line therapies in patients with metastatic renal cell carcinoma (mRCC) with the potential for eliciting long-lasting remissions. With the expanding arsenal of ICB-based therapies, biomarkers of response are urgently needed to guide optimal therapeutic selection. We review the data behind ICB therapy in RCC, emerging biomarkers of response, and the evolving role of surgery in patients with mRCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Ensaios Clínicos como Assunto , Humanos , Neoplasias Renais/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
J Med Econ ; 24(1): 291-298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33538203

RESUMO

BACKGROUND: Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P + A), and nivolumab plus ipilimumab (N + I) as first-line treatments, from the Brazilian private perspective. METHODS: Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P + A and N + I, respectively, versus sunitinib as mRCC first-line treatment. RESULTS: Considering a 12-month time horizon, 6 patients should be treated with P + A to prevent one death with sunitinib use, resulting in a COPE of 3,773,865 BRL. Using N + I, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing P + A versus sunitinib, with an estimated COPE of 3,773,865 BRL. Estimated NNT was 20 comparing N + I and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. CONCLUSION: At the 12-month landmark, P + A suggests better economic scenario versus N + I as first-line mRCC treatment option for intermediate- and poor-risk groups, through an indirect comparison using sunitinib as a common comparator.


Assuntos
Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Axitinibe/economia , Axitinibe/uso terapêutico , Brasil , Carcinoma de Células Renais/patologia , Análise Custo-Benefício , Feminino , Gastos em Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Ipilimumab/economia , Ipilimumab/uso terapêutico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Nivolumabe/economia , Nivolumabe/uso terapêutico , Intervalo Livre de Progressão , Índice de Gravidade de Doença , Sunitinibe/economia , Sunitinibe/uso terapêutico , Adulto Jovem
12.
Front Immunol ; 12: 627186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613575

RESUMO

After the COVID-19 outbreak, non-evidence based guidelines were published to advise clinicians on the adjustment of oncological treatment during this pandemic. As immune checkpoint inhibitors directly affect the immune system, concerns have arisen about the safety of immunotherapy during this pandemic. However, data on the immune response in oncology patients treated with immunotherapy are still lacking. Here, we present the adaptive immune response in a SARS-CoV-2 infected patient who was treated with immune checkpoint inhibitors for advanced renal cell cancer. To evaluate the immune response in this patient, the number of T cells and their major subsets were measured according to expression of markers for co-signalling, maturation, and chemotaxis at baseline, during therapy, and during the SARS-CoV-2 infection. In addition, plasma samples were analyzed for IgM and IgG antibodies and the ability of these antibodies to neutralise SARS-CoV-2. Despite several risk factors for an impaired immune response to SARS-CoV-2, both T- and B-cell responses were observed. Moreover, after treatment with immune checkpoint inhibitors, a sufficient cellular and humoral immune response was achieved in this SARS-CoV-2 infected patient. These findings warrant renewed discussion on withholding of immune checkpoint inhibitors during an ongoing COVID-19 pandemic.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Linfócitos B/imunologia , Carcinoma de Células Renais/diagnóstico , Imunoterapia/métodos , Ipilimumab/uso terapêutico , Neoplasias Renais/diagnóstico , Nivolumabe/uso terapêutico , Linfócitos T/imunologia , Anticorpos Antivirais/sangue , Carcinoma de Células Renais/tratamento farmacológico , Células Cultivadas , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Neoplasias Renais/tratamento farmacológico , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
13.
Zhonghua Bing Li Xue Za Zhi ; 50(2): 97-102, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33535302

RESUMO

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of hybrid oncocytic/chromophobe tumor (HOCT) of the kidney and its associations with renal oncocytoma (RO) and eosinophilic chromophobe renal cell carcinoma (eChRCC). Methods: A total of 8 HOCT cases were collected from 2008 to 2019 at the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of PLA Navy (3 cases), Qingdao, China for morphological studies, immunohistochemical staining and follow-up. The immunohistochemical results of HOCT were compared with those of 27 typical RO and 17 eChRCC. Results: Among the 8 patients, 3 were male and 5 were female. Their ages ranged from 39 to 75 years (median: 56 years). All cases were sporadic. Seven patients were asymptomatic and one suffered from lumbago. During a mean follow-up of 37 months in 7 patients, none of them developed tumor recurrence or metastasis. Seven cases were solitary and one was multiple. The tumor size ranged from 1.4 to 5.7 cm (mean, 3.6 cm). The cut surface of the tumors was dark red or yellowish. Histologically, the tumors were well-defined. Six cases were directly adjacent to the surrounding renal tissue, 2 cases had pseudocapsule, 3 cases showed entrapped renal tubules at the edge of tumor tissue, and one circumscribed with focal infiltrating borders. There were two types of histological morphology: one type (4 cases) was composed of mixed areas of otherwise typical RO and areas resembling chromophobe renal cell carcinoma; another type (4 cases) showed the morphological characteristics of both RO and eChRCC. Three second-type tumors showed nest-like, trabecular, and solid growth patterns with conspicuous edematous stroma. The cell border was conspicuous and the cytoplasm showed an eosinophilic appearance. The nuclei were small and round with clear perinuclear halo. One tumor showed a multi-nodular and solid growth pattern, and the cytoplasm was eosinophilic, hypochromatic or transparent. The nuclei were small and round, and some of them had obvious perinuclear halo. Immunohistochemically, the tumor cells in all 8 cases were positive for Ksp-cad but negative for vimentin. CD117 was diffusely positive in 6/8 cases. CK7 staining showed patchy positivity in 6/8 cases. S-100A1, cyclin D1 and claudin7 showed variable positivity in 4/8, 6/8 and 5/8 cases, respectively, but the range and intensity were narrower and weaker than those in RO and eChRCC. Conclusions: HOCT is a low-grade eosinophilic renal tumor with morphological characteristics resembling RO and eChRCC. The combined application of immunohistochemical stains of CK7, CD117, Ksp-cad, cyclin D1, claudin7 and S-100A1 may play an auxiliary role in the differentiation of the three tumors. HOCT has a good prognosis after surgical resection and can be regarded as a tumor with uncertain malignant potential.


Assuntos
Adenoma Oxífilo , Carcinoma de Células Renais , Neoplasias Renais , Adenoma Oxífilo/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma de Células Renais/diagnóstico , China , Diagnóstico Diferencial , Feminino , Humanos , Rim , Neoplasias Renais/diagnóstico , Masculino , Pessoa de Meia-Idade , Vimentina
14.
Zhonghua Bing Li Xue Za Zhi ; 50(2): 103-107, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33535303

RESUMO

Objective: To investigate the clinicopathological features, differential diagnosis and molecular characteristics of clear cell renal cell carcinoma (ccRCC) with hemangioblastoma component (ccRCC-HBc). Methods: Two ccRCC-HBc cases diagnosed at Fujian Provincial Hospital in September 2015 and March 2016, respectively, were included. Their morphological, immunohistochemical and molecular features were analyzed, including fluorescence in situ hybridization (FISH) detection of TFE3, TFEB and VHL genes. Related literature was reviewed to reveal the characteristics of this tumor. Results: The two cases occurred in 2 women, aged 33 and 66 years, respectively. The maximum diameters of the tumors were 4.0 cm and 8.5 cm, respectively. Histologically, the ccRCC component, representing approximate 10%-20% of the neoplasm, while the tumor cells arranged in flaky, nested, and solid distribution. The tumor cells had conspicuous nucleoli, with rich thin-wall capillary network in the stroma. The hemangioblastoma-like component, representing approximate 60%-70% of the neoplasm, showed a rich capillary network of single-layered flat endothelial cells enclosing stromal cells. The latter cell type showed a pale or eosinophilic cytoplasm exhibiting occasional lipid droplets. Rare cell nuclei appeared enlarged, pleomorphic, or bizarre. The two components were intermingled with each other. Immunohistochemically, the tumor cells were positive for PAX8, CKpan, EMA, vimentin, CD10, RCC, CAⅨ, and P504s in ccRCC area; in another area, the tumor cells were positive for α-inhibin, CD34 and vimentin, while CD10 were weakly positive. Neither TFE3 or TFEB gene split signal was detected in the 2 cases (0/2), nor was VHL gene mutation in case 2 (0/1). Conclusion: ccRCC-HBc is an extremely rare entity of ccRCC. The diagnosis is mainly based on clinical and pathological characteristics, as well as immunohistochemistry. Molecular pathology is helpful for its differential diagnosis. The primary approach of treating ccRCC-HBc is complete surgical excision and chemotherapy. The targeted treatment is helpful if possible.


Assuntos
Carcinoma de Células Renais , Hemangioblastoma , Neoplasias Renais , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Diagnóstico Diferencial , Células Endoteliais , Feminino , Hemangioblastoma/diagnóstico , Hemangioblastoma/genética , Hemangioblastoma/cirurgia , Humanos , Hibridização in Situ Fluorescente , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Pessoa de Meia-Idade
15.
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
16.
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
17.
Medicine (Baltimore) ; 100(3): e23956, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545974

RESUMO

BACKGROUND: The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of adjuvant targeted therapy by sunitinib combined with surgery in the treatment of advanced or metastatic renal cell carcinoma. METHODS: PubMed/Medline, Web of Science, Cochrane Library, ClinicalTrials.gov (http://www.ClinicalTrials.gov), China National Knowledge Infrastructure (CNKI) will be searched for clinical research articles related to the efficacy and safety of adjuvant therapy combined with surgery in the treatment of advanced and metastatic RCC. The identification, inclusion and exclusion flow charts will be conducted according to the PRISMA guidelines. The quality assessment will be done by Quadas-2 evaluation tool. Key parameters including OS in 10, 20, 30, and 40 months, PFS in 10, 20, and 30 months, objective response rate (ORR), stable disease (SD) rate, progressive disease (PD) rate, median OS and PFS, types of AEs and their occurrence rates, etc will be extracted. The evaluation of the efficacy and safety will be pooled by CMA. RESULTS: This systematic review will provide evidence on the efficacy and safety of adjuvant therapy by sunitinib combined with surgery in treating advanced and metastatic RCC. CONCLUSION: The study aims to generalize data concerning the response rate, OS, PFS and rates of adverse effects of the perioperative use of sunitinib in advanced and metastatic RCC patients. The evidence provided by this systematic review and meta-analysis will help guide the clinical decision making and enlighten the future management of advanced or metastatic RCC. REGISTRATION: This protocol has been registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY registration number: INPLASY2020110093; INPLASY DOI number: 10.37766/inplasy2020.11.0093 Available at: https://inplasy.com).


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Quimioterapia Adjuvante/normas , Protocolos Clínicos , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante/métodos , Humanos , Metanálise como Assunto , Sunitinibe/uso terapêutico , Revisões Sistemáticas como Assunto
18.
Medicine (Baltimore) ; 100(3): e24037, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546003

RESUMO

RATIONALE: Gallbladder polyps are common in the general population, but gallbladder metastasis of renal cell carcinoma (RCC) is very rare. In a patient with RCC diagnosed with a small gallbladder polyp that does not meet the traditional size criteria, the surgeon faces a dilemma of whether cholecystectomy should be performed given the possibility of metastasis. PATIENT CONCERNS: A 55-year-old man who had received a left nephrectomy for RCC presented with a gallbladder polyp that was noted at the time of the nephrectomy. Imaging showed the maximum diameter of the polyp had increased from 5 mm to 24 mm in the 40 months after the initial diagnosis. DIAGNOSIS: Pathological and immunohistology findings confirmed the gallbladder polyp as a metastasis of clear-cell RCC. INTERVENTIONS: : We performed a laparoscopic cholecystectomy. OUTCOMES: Even though the synchronous solitary gallbladder metastasis was left untreated and a cholecystectomy was not performed over the 40 months, no metastasis occurred in other sites. The patient is free from disease 10 months after the cholecystectomy. LESSONS: Solitary gallbladder metastasis of RCC may have more favorable outcomes than typical metastases. Although gallbladder metastasis of RCC occur rarely, it can occur, and any changes in gallbladder polyps in RCC patients should be managed under a strong suspicion of metastasis.


Assuntos
Carcinoma de Células Renais/secundário , Doenças da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/secundário , Neoplasias Renais/patologia , Pólipos/patologia , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/cirurgia , Colecistectomia/métodos , Vesícula Biliar/patologia , Vesícula Biliar/cirurgia , Doenças da Vesícula Biliar/etiologia , Doenças da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Pólipos/etiologia , Pólipos/cirurgia
19.
Acta Cytol ; 65(2): 140-149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33535202

RESUMO

BACKGROUND: Fine needle aspiration (FNA) of renal masses can distinguish between benign and malignant neoplasms in 73-94% of cases. Previous studies suggested the correct subclassification of renal cell carcinomas (RCCs) by cytomorphology can be achieved in up to 80% of cases. However, as RCCs become increasingly subclassified by molecular signatures, correct subclassification based on cytology alone is increasingly difficult. DESIGN: Two FNA passes (2 stained with Diff-Quik® and 2 with the Papanicolaou method) were performed on all fresh nephrectomy specimens for a 1-year period. There were 30 cases in this study, with 29 primary renal tumors and 1 case of metastatic lung adenocarcinoma. Each case was assigned a random number and came with 2 slides (1 from each staining method). Eight cytopathologists were asked to provide a diagnosis and the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading if applicable. Fleiss' Kappa and Cohen's Kappa equations were used to look at inter-rater variability. RESULTS: When compared to the surgical pathology diagnosis, the average percent correct diagnosis for all cytopathologist was 35%. Chromophobe RCCs had the best average percent accuracy at 72% followed by clearcell RCC at 48%. Average accuracy for grading RCCs was 40%. Inter-rater variability among the cytopathologists for all RCC diagnoses was fair with a Fleiss' Kappa coefficient of 0.28. For the WHO/ISUP grade, the weighted coefficient for each pathologist ranged from 0.11 to 0.45, ranging from fair to moderate, respectively. CONCLUSIONS: Renal tumors are difficult to classify on cytopathology alone. Core needle biopsy and ancillary studies are necessary if diagnosis will change management.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Corantes Azur , Biópsia por Agulha Fina , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/cirurgia , Azul de Metileno , Gradação de Tumores , Variações Dependentes do Observador , Teste de Papanicolaou , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Xantenos
20.
Crit Rev Oncol Hematol ; 159: 103242, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33545356

RESUMO

OBJECTIVE: To conduct a systematic review and meta-analysis of the role of SBRTdrug combination in patients affected by mRCC and associated oncologic outcomes and toxicity profiles. EVIDENCE ACQUISITION: We performed a critical review of the Pubmed, Medline, and Embase databases from January 1, 2000 through April 30, 2020 according to the Preferred Reporting Items and Meta-Analyses statement. To assess the overall quality of the literature reviewed, we used a modified Delphi tool. EVIDENCE SYNTHESIS: A total of 6 studies were included, corresponding to a cohort of 216 patients. Tyrosine Kinases Inhibitors were the most widely used drugs in combination with SBRT, being administered in 93% patients. No study reported an increase of radiation-induced toxicity. CONCLUSIONS: SBRT resulted to be safe, without increase in terms of drugs-related adverse events in this setting. Moreover, this approach showed promising clinical outcomes in terms of LC and OS.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Preparações Farmacêuticas , Radiocirurgia , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Radiocirurgia/efeitos adversos
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