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1.
Niger J Clin Pract ; 23(10): 1483-1486, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33047710

RESUMO

Metastatic lesions represent approximately 1% of all the intraoral lesions. They most commonly originate from lung and breast carcinomas, while the third most common source is the renal cell carcinoma. In this paper, we present the rare case of metastases of renal cell carcinoma in the mandibular gingiva of a 53-year-old male patient.


Assuntos
Carcinoma de Células Renais/secundário , Gengiva/patologia , Neoplasias Gengivais/secundário , Neoplasias Renais/patologia , Dor nas Costas , Biópsia , Carcinoma de Células Renais/patologia , Neoplasias Gengivais/patologia , Cabeça/diagnóstico por imagem , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Pescoço/diagnóstico por imagem
3.
Am J Clin Oncol ; 43(9): 621-627, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889831

RESUMO

OBJECTIVES: Despite the initial clinical benefit, resistance to antiangiogenic therapies develops through the activation of alternative pathways. We measured plasma levels of circulating angiogenic factors to explore their predictive role in metastatic renal cell carcinoma (mRCC) patients treated with pazopanib. MATERIALS AND METHODS: mRCC patients receiving first-line pazopanib were prospectively enrolled. The levels of circulating interleuchine (IL)-6, IL-8, stromal derived factor-1, vascular endothelial growth factor-A, hepatocyte growth factor (HGF), osteopontin, and E-selectin were quantified at baseline and every 4 weeks until disease progression (PD). Patients were dichotomized into "low" and "high" subgroups by a cutoff point defined by the respective median circulating angiogenic factor (CAF) value at baseline. Then, association with the objective response was determined. Changes in CAF levels between baseline and PD were also compared. RESULTS: Among 25 patients included in the final data set, 6 patients were still on treatment. As best response, 12 patients presented a partial response (48%), 9 showed stable disease, and 4 showed PD. The median follow-up was 31.9 months. The median progression-free survival was 14.8 months. Low baseline levels of IL-6, IL-8, HGF, and osteopontin were found to be significantly associated with objective response. In addition, patients with low baseline levels of HGF showed longer progression-free survival and overall survival, whereas patients with low baseline levels of IL-8 showed longer overall survival. Among patients experiencing PD, the median plasma levels of stromal derived factor-1 and vascular endothelial growth factor-A were significantly higher compared with the baseline (P=0.01; P=0.011). Conversely, the median levels of E-selectin were significantly lower compared with the baseline (P=0.017). CONCLUSION: Changes in levels of selected CAFs were associated with response/resistance to pazopanib in mRCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/secundário , Quimiocina CXCL12/sangue , Progressão da Doença , Selectina E/sangue , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Intervalo Livre de Progressão , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores Sólidos , Taxa de Sobrevida , Pesquisa Médica Translacional , Fator A de Crescimento do Endotélio Vascular/sangue
4.
Urol Clin North Am ; 47(3): 281-291, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600531

RESUMO

Patients with renal cell carcinoma may develop metastases after radical nephrectomy, and therefore monitoring with imaging for recurrent or metastatic disease is critical. Imaging varies with specific suspected site of disease. Computed tomography/MRI of the abdomen and pelvis are mainstay modalities. Osseous and central nervous system imaging is reserved for symptomatic patients. Radiologic reporting is evolving to reflect effects of systemic therapy on lesion morphology. Nuclear medicine studies compliment routine imaging as newer agents are evaluated for more accurate tumor staging. Imaging research aims to fill gaps in treatment selection and monitoring of treatment response in metastatic renal cell carcinoma.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Carcinoma de Células Renais/secundário , Humanos , Neoplasias Renais/patologia
5.
Urol Clin North Am ; 47(3): 379-388, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32600539

RESUMO

Surgical metastasectomy continues to be utilized for patients with solitary or low-volume metastatic renal cell carcinoma (mRCC). Although few high-quality data are available to evaluate outcomes, local treatment is recommended when feasible because it may allow a subset of patients to delay or avoid systemic treatments. With the development of improved mRCC therapies, utilization of metastasectomy has increased because most patients have incomplete responses to systemic treatment of their metastases. This review discusses the rationale and history of metastasectomy, trends in utilization, prognostic factors for patient selection, site-specific considerations, alternatives for nonsurgical local treatment, and risk of morbidity associated with metastasectomy.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Metastasectomia/métodos , Carcinoma de Células Renais/secundário , Humanos , Neoplasias Renais/patologia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Estadiamento de Neoplasias , Nefrectomia
6.
Bull Cancer ; 107(5S): S24-S34, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32620204

RESUMO

The standard of care for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically over the past decades thanks to the increasing number of treatments: anti-VEGFR tyrosine kinase inhibitors (TKI), mTOR inhibitors and immune checkpoint inhibitors (ICI): anti PD(L)-1 used as monotherapy or in combination with anti CTLA-4 or anti angiogenic therapies. In the face of rising therapeutic options, the question of the therapeutic sequences arises: which treatment for which patient? Actually, there is a lack of predictive biomarkers. A greater understanding of the cancer biology and its interaction with the microenvironment has allowed the development of genomic signatures which could perhaps be used as predictive biomarker. This review will give an insight on some robust genomic signatures assessed in mccRCC and will have a closer look at BIONIKK phase II trial, which is the first trial to adapt treatments according to the molecular characteristics of the tumor in the context of mccRCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Carcinoma de Células Renais/secundário , Tomada de Decisão Clínica , Humanos , Neoplasias Renais/patologia , Guias de Prática Clínica como Assunto
7.
ESMO Open ; 5(Suppl 3)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669298

RESUMO

BACKGROUND: The coronavirus pandemic has provoked discussions among healthcare providers how to manage cancer patients when faced with the threat of severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) infection. Immune checkpoint inhibitor (ICI) containing regimens are standard of care in the majority of metastatic clear cell renal cell carcinoma (mccRCC) patients. It remains unclear whether therapies should be modified in response to the COVID-19 pandemic. METHODS: We performed an online survey among physicians involved in the treatment of mccRCC, and 41 experts responded. Questions focused on criteria relevant for treatment decision outside the pandemic and the modifications of systemic therapy during COVID-19. FINDINGS: For the majority of experts (73%), the combination of International metastatic renal cell carcinoma Database Consortium (IMDC) risk category and patient fitness are two important factors for decision-making. The main treatment choice in fit, favourable risk patients outside the pandemic is pembrolizumab/axitinib for 53%, avelumab/axitinib, sunitinib or pazopanib for 13% of experts each. During the pandemic, ICI-containing regimens are chosen less often in favour of a tyrosine kinase inhibitors (TKI) monotherapy, mainly sunitinib or pazopanib (35%).In fit, intermediate/poor-risk patients outside the pandemic, over 80% of experts choose ipilimumab/nivolumab, in contrast to only 41% of physicians during COVID-19, instead more TKI monotherapies are given. In patients responding to established therapies with ICI/ICI or ICI/TKI combinations, most participants modify treatment regimen by extending cycle length, holding one ICI or even both. CONCLUSION: mccRCC treatment modifications in light of the coronavirus pandemic are variable, with a shift from ICI/ICI to ICI/TKI or TKI monotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Neoplasias Renais/tratamento farmacológico , Pneumonia Viral/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Betacoronavirus , Carcinoma de Células Renais/secundário , Tomada de Decisão Clínica , Infecções por Coronavirus/prevenção & controle , Humanos , Fatores Imunológicos/uso terapêutico , Neoplasias Renais/patologia , Oncologia/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Inibidores de Proteínas Quinases/uso terapêutico , Urologia/estatística & dados numéricos
8.
Crit Rev Oncol Hematol ; 152: 102971, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32497970

RESUMO

The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone a substantial evolution in the past decade, with a dramatic increase in the number of available systemic therapies. Although this offers promise for improved patient outcomes, this rapid pace in development has led to new challenges in therapeutic choice. For instance, the absence of direct comparative evidence across all therapeutic options has led to a critical gap in evidence to clearly define preferred systemic therapy choice. Additionally, the rising cost of systemic therapies being evaluated for mRCC necessitates demonstration of cost-effectiveness prior to widespread adoption. This review provides an overview of the current treatment landscape in mRCC to highlight the emerging challenges faced by clinicians and health policy-makers. In addition, this review summarizes the currently available evidence that aims to address the above challenges.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Humanos , Imunoterapia , Neoplasias Renais/terapia , Terapia de Alvo Molecular , Metástase Neoplásica
9.
Khirurgiia (Mosk) ; (6): 118-120, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32573543

RESUMO

Small bowel tumor causes gastrointestinal bleeding in 1-4% of cases. Gastrointestinal bleeding from metastases of renal cell carcinoma is a rare and little-known manifestation of this disease. We report a rare clinical case of a solitary metastasis of clear cell renal cell carcinoma into small bowel in 5 years after nephrectomy. The first symptom was intestinal bleeding. This example emphasizes the need for more thorough examination of patients with symptoms of latent and anamnestic blood loss.


Assuntos
Carcinoma de Células Renais/secundário , Hemorragia Gastrointestinal/etiologia , Neoplasias Intestinais/secundário , Neoplasias Renais/patologia , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Intestinais/complicações , Intestino Delgado , Neoplasias Renais/cirurgia , Nefrectomia
10.
J Vasc Interv Radiol ; 31(8): 1242-1248, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32522505

RESUMO

PURPOSE: The purpose of this study was to evaluate the effectiveness and adverse outcomes of percutaneous cryoablation (CA) for treatment of renal masses in a large cohort of patients. MATERIALS AND METHODS: This retrospective analysis included 299 CA procedures (297 masses in 277 patients) performed between July 2007 and May 2018 at a single institution. The mean patient age was 66.1 years (range, 30-93 years) with 65.8% being male. A total of 234 (78.8%) masses were biopsy-proven renal cell carcinoma (RCC). The mean maximal tumor diameter was 2.5 cm (range, 0.7-6.6 cm). Efficacy was assessed only for ablations of biopsy-proven RCC, whereas the evaluation of adverse events and renal function included all masses. Complications were graded according to the Society of International Radiology classification. RESULTS: Major complications occurred in 3.0% of procedures (n = 9), none of which resulted in death or permanent disability. The mean imaging follow-up period was 27.4 months (range, 1-115) for the 199 RCC patients (204 ablated tumors) with follow-up imaging available. Complete response on initial follow-up imaging at mean 4.2 months (range, 0.3-75.6) was achieved in 195 of 204 tumors (95.6%) after a single session and in 200 of 204 tumors (98.0%) after 1 or 2 sessions. Of the RCC patients achieving complete response initially, local recurrence during the follow-up period occurred in 3 of 200 tumors (1.5%). Metastatic progression occurred in 10 of 193 (5.2%) RCC patients without prior metastatic disease during follow-up. CONCLUSIONS: CA for renal masses is safe and remains efficacious through intermediate- and long-term follow-up.


Assuntos
Carcinoma de Células Renais/cirurgia , Criocirurgia , Neoplasias Renais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Células Renais/secundário , Criocirurgia/efeitos adversos , Progressão da Doença , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
13.
World Neurosurg ; 139: 483-487, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360731

RESUMO

BACKGROUND: Immuno-oncotherapy (IO) has revolutionized systemic cancer care but remains experimental in brain tumors. IO treatment risks multiorgan autoimmune inflammatory responses that limit its use. The central nervous system (CNS) is an immune-specialized compartment with restricted cellular access, thus fewer cases are reported for immune-mediated encephalitis. Interestingly, patients with history of blood-brain barrier compromise are potentially at higher risk for immune cell trafficking to the CNS. CASE DESCRIPTION: We report the first case, to our knowledge, of a 70-year-old man with clear cell renal cell carcinoma with pulmonary metastases treated with lung irradiation, nephrectomy, and chemotherapy prior to switching to single-agent nivolumab IO. The patient presented with new-onset generalized tonic-clonic seizure and left visual field-cut. Review of patient history revealed remote traumatic brain injury (TBI). Brain imaging noted a solid-enhancing right occipital mass that was presumed metastasis versus lymphoma. Cerebrospinal fluid cytology was negative for malignancy but concerning for lymphoproliferative process not determined to be malignant. The patient started steroids and anti-epileptic therapy. After negative systemic cancer re-staging, IO was discontinued and steroids were initiated with demonstrated patient clinical improvement. CONCLUSIONS: We concluded the diagnosis of immune-mediated encephalitis secondary to IO with collection of reactive T-cells within the area of encephalomalacia. The area of encephalomalacia from prior TBI served to compartmentalize the reactive lymphocytes, giving the appearance of a mass. Taken together, new onset seizure in patients on IO might signal encephalitis and CNS metastatic mimicry should be considered in patients with a prior history of TBI and encephalomalacia.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Encefalite/induzido quimicamente , Encefalite/diagnóstico por imagem , Idoso , Lesões Encefálicas Traumáticas/complicações , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Diagnóstico Diferencial , Encefalite/complicações , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Nivolumabe/efeitos adversos
14.
Am J Clin Oncol ; 43(8): 559-566, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32398404

RESUMO

OBJECTIVES: Treatments for metastatic renal cell carcinoma (mRCC) are often compared across trials, but trial eligibility criteria and endpoints differ. In an effort to better align trials, the Definition for the Assessment of Time to event Endpoints in CANcer trials (DATECAN) project published recommendations in 2015 to be used in mRCC clinical trial design. We analyzed mRCC trial criteria to determine if DATECAN's recommendations were followed. MATERIALS AND METHODS: We compared eligibility criteria across 29 phase 3 mRCC trials conducted between 2003 and 2019. We then evaluated endpoints used in 10 phase 3 trials activated between 2015 and 2019 to determine their compliance with DATECAN's recommendations. RESULTS: Among the 29 trials, performance status, renal function, and disease characteristics differed in terms of requirements and measures used. In terms of endpoints, the 10 trials did not entirely follow DATECAN's recommendations. In total, 7/10 trials' primary endpoint was progression-free survival (PFS) as recommended; 4/9 trials used PFS as an endpoint but did not publish their definition of PFS, and the 5 that did, included "death from any cause" instead of DATECAN's recommendation of "death from kidney cancer." CONCLUSIONS: Key eligibility criteria were somewhat inconsistent across the phase 3 mRCC trials studied. Endpoints in the newer trials did not align with DATECAN's recommendations. Not only is greater standardization needed to facilitate meta-analyses and cross-trial comparisons, but as evident from lack of adherence to DATECAN's recommendations, greater promotion and adoption of recommendations are needed to better harmonize trial design.


Assuntos
Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Definição da Elegibilidade/normas , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Humanos
15.
Nat Cell Biol ; 22(4): 476-486, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32231310

RESUMO

SLC7A11-mediated cystine uptake is critical for maintaining redox balance and cell survival. Here we show that this comes at a significant cost for cancer cells with high levels of SLC7A11. Actively importing cystine is potentially toxic due to its low solubility, forcing cancer cells with high levels of SLC7A11 (SLC7A11high) to constitutively reduce cystine to the more soluble cysteine. This presents a significant drain on the cellular NADPH pool and renders such cells dependent on the pentose phosphate pathway. Limiting glucose supply to SLC7A11high cancer cells results in marked accumulation of intracellular cystine, redox system collapse and rapid cell death, which can be rescued by treatments that prevent disulfide accumulation. We further show that inhibitors of glucose transporters selectively kill SLC7A11high cancer cells and suppress SLC7A11high tumour growth. Our results identify a coupling between SLC7A11-associated cystine metabolism and the pentose phosphate pathway, and uncover an accompanying metabolic vulnerability for therapeutic targeting in SLC7A11high cancers.


Assuntos
Sistema y+ de Transporte de Aminoácidos/genética , Carcinoma de Células Renais/genética , Cistina/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Via de Pentose Fosfato/genética , Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Sistema y+ de Transporte de Aminoácidos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dissulfetos/metabolismo , Fármacos Gastrointestinais/farmacologia , Glucose/deficiência , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/antagonistas & inibidores , Transportador de Glucose Tipo 3/genética , Transportador de Glucose Tipo 3/metabolismo , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Camundongos , Camundongos Nus , Fosfogluconato Desidrogenase/genética , Fosfogluconato Desidrogenase/metabolismo , Pirazóis/farmacologia , Quinolinas/farmacologia , Estresse Fisiológico , Sulfassalazina/farmacologia , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Clin Interv Aging ; 15: 431-439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256058

RESUMO

Objective: To explore the survival value of cytoreductive partial nephrectomy (cPN) in elderly with metastatic renal cell carcinoma (EmRCC) and evaluate the characteristics of patients who benefit from cPN. Materials and Methods: This was a study including 6105 patients aged ≥65 years with metastatic renal cell carcinoma (RCC) queried from Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015, among which 1264 patients underwent cytoreductive nephrectomy (CN), 78 patients underwent cPN and 1186 patients underwent cytoreductive radical nephrectomy (cRN). Kaplan-Meier (K-M) method and Cox proportional-hazards model (COX) were used to evaluate the survival prognosis. Overall survival (OS) was compared between groups using propensity score matching (PSM) to balance the effects of confounding factors such as general features and pathological features. At last, we constructed a nomogram visualization modelled by R language to predict survival. Results: For patients with EmRCC, especially for male patients with tumors size ≤7 cm, N0 stage, or isolated metastases, cPN brought a better survival than cRN. Tumor size and N stage were independent risk factors affecting the survival of cPN patients. cPN for patients with tumor size >7 cm or N1 stage may present a higher risk of death. Conclusion: The implementation of cPN for patients with EmRCC who meet specific clinical characteristics such as tumors size ≤7 cm, N0 stage, or isolated metastases seems to help improve the survival prognosis.


Assuntos
Carcinoma de Células Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Neoplasias Renais/cirurgia , Nefrectomia/estatística & dados numéricos , Idoso , Carcinoma de Células Renais/secundário , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Fatores de Risco , Resultado do Tratamento
17.
Am J Surg Pathol ; 44(8): 1031-1039, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32271189

RESUMO

Acquired cystic disease of kidney-associated renal cell carcinoma (ACD-RCC) is a distinct subtype of renal cell carcinoma with unique morphologic and clinicopathologic features. Generally, ACD-RCC is regarded as an indolent tumor; however, prognostic and outcomes data have been conflicted by the limited and relatively low number of cases with patient follow-up or adverse events. In this study, we focused on the histology of metastatic lesions and identifying prognostic factors associated with metastatic progression. From 32 cases in the cohort, 9 patients had metastasis [ACD-RCC (M+)] and 23 patients were without metastasis [ACD-RCC (M-)]. The median age of patients was 52 years; right side, n=10; left side, n=18; bilateral, n=4; median tumor size=2.6 cm; median hemodialysis duration=17 y; and the median duration of follow-up was 50 mo. Immunohistochemistry showed ACD-RCC to be racemase positive and CK7 negative to focally positive within tumor cells, with consistent positivity for renal histogenesis-associated markers (PAX8 and RCC antigen); S100A1 was a less reliable marker at metastatic sites. All metastatic ACD-RCC except 2 cases involved lymph nodes (para-aortic, renal hilar, subclavicular). Overall, 6/9 (67%) had visceral metastasis to sites including lung (n=3), liver (n=3), bone (n=5), stomach (n=1), and brain (n=1). In total, 5/9 (56%) metastatic tumors had distinctive cystic growth pattern at the metastatic site; intriguingly metastatic tumors had intrametastatic oxalate crystal deposition, a pathognomonic feature associated with primary tumors. Four of nine (44%) patients with ACD-RCC (M+) had fatal outcomes due to metastatic disease. Clinically significant adverse prognostic features associated with metastasis [median follow-up 47 mo, ACD-RCC (M+) vs. ACD-RCC (M-), 50 mo] included: duration of hemodialysis (≥20 vs. <20 y, P=0.0085) and tumor necrosis (P=0.049). Because of sufficient overlap between these parameters, the study was not able to identify parameters that would be reliable in further management strategies, in clinical settings. Our data indicate that ACD-RCC is a tumor which has distinct metastatic potential with nodal and visceral tropism and proclivity for cystic morphology at metastatic sites; this is the first report of the presence of oxalate crystals in metastatic tumors. Our data suggest that ACD-RCC patients with prolonged hemodialysis and tumoral coagulative necrosis require additional surveillance in view of the association of these parameters with metastatic progression.


Assuntos
Carcinoma de Células Renais/secundário , Doenças Renais Císticas/complicações , Falência Renal Crônica/etiologia , Neoplasias Renais/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/química , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/terapia , Cristalização , Feminino , Humanos , Japão , Doenças Renais Císticas/diagnóstico , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Neoplasias Renais/química , Neoplasias Renais/etiologia , Neoplasias Renais/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Ácido Oxálico/análise , Prognóstico , Diálise Renal , Fatores de Risco
18.
Arch Esp Urol ; 73(2): 147-154, 2020 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-32124846

RESUMO

OBJECTIVE: Kidney cancer is around 2-3% of malignant tumours in adults. It has an important tendency to metastasize, being the most affected organs lungs, liver,brain, bone and adrenal glands. The pancreas is a rare site of kidney metastasis, with an incidence of 1-2.8%. The aim of this paper is to analyze the clinical diagnosis, treatment and prognosis of the pancreatic metastasis secondary to kidney cancer. METHOD: We present a retrospective descriptive analysis of 6 cases of pancreatic metastasis of primary kidney cancer diagnosed at Cruces University Hospital since 2011.We describe the cases individually also making a global analysis of the pathology and literature review. RESULTS: Two of the patients had pancreatic and extrapancreatic metastatic lesions, being treated systemic treatment without adjacent surgery. They showed an overall worse prognosis. The rest of the patients had only pancreatic disease,rational for surgical removal of all masses without need of further adjuvant treatment. The results after surgery were encouraging, with longer overall survival, progression free survival and better quality of life. CONCLUSIONS: Pancreatic metastases of kidney cancer are very rare and they can appear several years after nephrectomy. Patients with history of kidney cancer should be followed for long term after surgery. When metastases are limited to the pancreas, radical surgery has longer overall survival, progression free survival and better quality of life outcomes.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pancreáticas , Carcinoma de Células Renais/secundário , Humanos , Neoplasias Renais/patologia , Nefrectomia , Pancreatectomia , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/cirurgia , Qualidade de Vida , Estudos Retrospectivos
19.
Arch. esp. urol. (Ed. impr.) ; 73(2): 147-154, mar. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-192910

RESUMO

OBJETIVO: El cáncer renal constituye el 2-3% de los tumores malignos del adulto y tiene una gran tendenciaa metastatizar, siendo el pulmón, hígado, cerebro, hueso y suprarrenales los órganos diana más frecuentes. Sin embargo, también puede afectar a otros órganos más inusuales,como el páncreas, con una incidencia de 1-2,8%.El objetivo de este trabajo es analizar la presentación, tratamiento y pronóstico de las metástasis pancreáticas de cáncer renal. MÉTODO: Se realiza un análisis descriptivo retrospectivo de 6 casos de metástasis pancreáticas de tumor primario renal diagnosticados en el Hospital Universitario Cruces desde 2011. Se presentan los casos individualmente, se realiza un análisis global y revisión de la literatura. RESULTADO: En dos pacientes se objetivaron lesiones pancreáticas y extrapancreáticas, por lo que se decidió tratamiento sistémico, presentando estos pacientes un pronóstico peor. En el resto de los pacientes no se objetivó enfermedad extrapancreática, por lo que las lesiones pancreáticas se trataron quirúrgicamente, obteniendo una mejoría importante en la supervivencia, tiempo libre de enfermedad y calidad de vida, sin necesidad de tratamiento adyuvante. CONCLUSIONES: Las metástasis pancreáticas de cáncer renal son raras y pueden aparecer muchos años después de la nefrectomía, por lo que debería realizarse seguimiento a largo plazo en los pacientes con antecedentes de tumor renal. Cuando la enfermedad metastásica está limitada al páncreas, la cirugía radical mejora la supervivencia y calidad de vida de los pacientes


OBJECTIVE: Kidney cancer is around 2-3% of malignant tumours in adults. It has an important tendency to metastasize, being the most affected organs lungs, liver, brain, bone and adrenal glands. The pancreas is a rare site of kidney metastasis, with an incidence of 1-2.8%. The aim of this paper is to analyze the clinical diagnosis, treatment and prognosis of the pancreatic metastasis secondary to kidney cancer. METHOD: We present a retrospective descriptive análisis of 6 cases of pancreatic metastasis of primary kidney cancer diagnosed at Cruces University Hospital since 2011. We describe the cases individually also making a global analysis of the pathology and literature review. RESULTS: Two of the patients had pancreatic and extrapancreatic metastatic lesions, being treated systemic treatment without adjacent surgery. They showed an overall worse prognosis. The rest of the patients had only pancreatic disease, rational for surgical removal of all masses without need of further adjuvant treatment. The results after surgery were encouraging, with longer overall survival, progression free survival and better quality of life. CONCLUSIONS: Pancreatic metastases of kidney cancer are very rare and they can appear several years after nephrectomy. Patients with history of kidney cancer should be followed for long term after surgery. When metastases are limited to the pancreas, radical surgery has longer overall survival, progression free survival and better quality of life outcomes


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/cirurgia , Nefrectomia , Pancreatectomia , Qualidade de Vida , Estudos Retrospectivos
20.
Nat Cell Biol ; 22(4): 465-475, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203421

RESUMO

Advanced clear cell renal cell carcinoma (ccRCC) frequently causes systemic inflammation. Recent studies have shown that cancer cells reshape the immune landscape by secreting cytokines or chemokines. This phenotype, called cancer-cell-intrinsic inflammation, triggers a metastatic cascade. Here, we identified the functional role and regulatory mechanism of inflammation driven by advanced ccRCC cells. The inflammatory nature of advanced ccRCC was recapitulated in a preclinical model of ccRCC. Amplification of cancer-cell-intrinsic inflammation during ccRCC progression triggered neutrophil-dependent lung metastasis. Massive expression of inflammation-related genes was transcriptionally activated by epigenetic remodelling through mechanisms such as DNA demethylation and super-enhancer formation. A bromodomain and extra-terminal motif inhibitor synchronously suppressed C-X-C-type chemokines in ccRCC cells and decreased neutrophil-dependent lung metastasis. Overall, our findings provide insight into the nature of inflammatory ccRCC, which triggers metastatic cascades, and suggest a potential therapeutic strategy.


Assuntos
Carcinoma de Células Renais/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Animais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Linhagem Celular Tumoral , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Inflamação , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patologia , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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