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1.
Medicine (Baltimore) ; 99(41): e22206, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031263

RESUMO

BACKGROUND: Surgery for lung cancer squeezes the tumor, further promoting the circulation of tumor cells, which may be one of the reasons for lung cancer metastasis and recurrence. In theory, the potential risk of tumor cell proliferation can be minimized if the outflow veins are ligated first (via veins first [V-first]) rather than arteries first (via arteries first [A-first]). However, due to the lack of sufficient evidence, this technical concept has not been widely accepted as a standard in surgical oncology in the current guidelines. This systematic review and meta-analysis will be used to determine which techniques will yield longer patient survival and benefit patients during segmentectomy. METHODS: We will search PubMed, Web of Science, Embase, Cancerlit, the Cochrane Central Register of Controlled Trials, and Google Scholar databases for relevant clinical trials published in any language before January 1, 2021. Randomized controlled trials (RCTs), quasi-RCTs, propensity score-matched comparative studies, and prospective cohort studies of interest, published or unpublished, that meet the inclusion criteria will be included. Subgroup analysis of the type of operation, tumor pathological stage, and ethnicity will be performed. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: As far as we know, this study will be the first meta-analysis to compare the efficacy of the vein-first and artery-first surgical technique of segmentectomy for patients diagnosed with resectable non-small cell lung cancer. Due to the nature of the disease and intervention methods, RCTs may be inadequate, and we will carefully consider inclusion in high-quality, non-RCTs, but this may result in high heterogeneity and affect the reliability of the results.INPLASY registration number: INPLASY202080062.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Células Neoplásicas Circulantes/patologia , Artéria Pulmonar/cirurgia , Veias Pulmonares/cirurgia , Projetos de Pesquisa , Humanos , Ligadura , Metanálise como Assunto , Pneumonectomia , Fatores de Risco , Revisões Sistemáticas como Assunto
2.
Med Sci (Paris) ; 36(10): 872-878, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-33026329

RESUMO

Metastases are the main cause of cancer-related deaths. The chain of events leading to their development is called "the metastatic cascade". The biological and biochemical aspects of this process have been well studied but the importance of biomechanical parameters only recently became a focus in the field. Studies have shown the biological fluids (blood, lymph and interstitial fluid) to play a key role in the metastatic cascade. These fluids participate in the transport of circulating tumor cells (CTCs) as well as the factors that they secrete, while at the same time influencing the events of the metastatic cascade through the forces that they generate. The hemodynamic properties and topological constraints of the vascular architecture control the formation of metastatic niches and the metastatic potential of tumor cells. In this review, we discuss the importance of these mechanical forces and highlight the novel questions and research avenues that they open.


Assuntos
Líquido Extracelular/fisiologia , Hidrodinâmica , Metástase Neoplásica/patologia , Metástase Neoplásica/fisiopatologia , Células Neoplásicas Circulantes/patologia , Fenômenos Biomecânicos , Líquido Extracelular/química , Humanos , Microambiente Tumoral/fisiologia
3.
Medicine (Baltimore) ; 99(40): e22242, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019399

RESUMO

BACKGROUND: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis. RESULTS: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57-0.63), 0.95 (95%CI = 0.93-0.96), 0.36 (95%CI = 0.28-0.48), 11.64 (95%CI = 5.85-23.14), and 38.94 (95%CI = 18.33-82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55-3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89-4.86; P < .01). CONCLUSION: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais , Carcinoma Hepatocelular/sangue , Contagem de Células , Humanos , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia , Células Neoplásicas Circulantes/patologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e Especificidade , Análise de Sobrevida
4.
Anticancer Res ; 40(10): 5577-5582, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988881

RESUMO

BACKGROUND/AIM: Clusters of circulating tumor cells (CTCs) increase metastatic potential compared to single CTC. However, conventional technologies have been unable to generate an accurate analysis of single and cluster CTCs in the peripheral blood. We propose an effective strategy to detect and isolate both single and cluster CTCs using two size-selective microfilters. MATERIALS AND METHODS: Five ml of whole blood were collected from 10 patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer. Single and cluster CTCs were identified using precision microfiltration membranes with two distinct pore sizes together with anti-EpCAM antibody labeling. RESULTS: Single and cluster CTCs were detected by simultaneously using two size-selective microfilters. The EGFR-L858R mutation was detected in the DNA from cells captured using both microfilters. CONCLUSION: Our method can be used to detect and isolate single and cluster CTCs in the whole blood and may facilitate the development of a liquid biopsy strategy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , DNA Tumoral Circulante/sangue , Molécula de Adesão da Célula Epitelial/sangue , Células Neoplásicas Circulantes/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Separação Celular , Feminino , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Mutação/genética , Células Neoplásicas Circulantes/patologia
5.
Anticancer Res ; 40(10): 5679-5685, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988893

RESUMO

BACKGROUND/AIM: The presence of circulating tumor cells (CTC) has been reported to have an impact on prognosis in different tumor entities. Little is known about CTC morphology and heterogeneity. PATIENTS AND METHODS: In a multicenter setting, pre-therapeutic peripheral blood specimens were drawn from patients with non-metastatic esophageal adenocarcinoma (EAC). CTCs were captured by size-based filtration (ScreenCell®), subsequently Giemsa-stained and evaluated by two trained readers. The isolated cells were categorized in groups based on morphologic criteria. RESULTS: Small and large single CTCs, as well as CTC-clusters, were observed in 69.2% (n=81) of the 117 specimens; small CTCs were observed most frequently (59%; n=69), followed by large CTCs (40%; n=47) and circulating cancer-associated macrophage-like cells (CAMLs; 34.2%, n=40). Clusters were rather rare (12%; n=14). CTC/CAML were heterogeneous in the cohort, but also within one specimen. Neither the presence of the CTC subtypes/CAMLs nor the exact cell count were associated with the primary clinical TNM stage. CONCLUSION: Morphologically heterogenic CTCs and CAMLs are present in patients with non-metastatic, non-pretreated EAC.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Neoplasias Esofágicas/sangue , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/patologia , Contagem de Células , Separação Celular , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/patologia , Prognóstico
6.
Anticancer Res ; 40(10): 5837-5844, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988913

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary tract. Venous migration, tumor thrombus and metastases are often seen in patients with RCC and are adverse prognostic factors. Intravascular tumor growth along the renal vein into the inferior vena cava occurs in up to 10% of all patients with RCC. Furthermore, extension of the tumor reaching the right atrium is detected in approximately 1% of all patients. Synchronous involvement of pulmonary arteries with tumor emboli is very rare and challenging. Management of metastatic RCC includes surgical resection of renal and metastatic lesions. We present 3 cases of patients with RCC tumor thrombus extending into the inferior vena cava (IVC) and with pulmonary emboli of the tumor thrombus into one of the branches of the main pulmonary artery. All the cases had simultaneous resection of the kidney tumor with the tumor thrombus and pulmonary lobectomy that included the tumor emboli with satisfactory outcome. CASE REPORT: We present a series of cases of RCC with tumor extension into the inferior vena cava (IVC) and with tumor emboli to the pulmonary arteries. Surgical procedure in all cases consisted of radical nephrectomy with IVC tumor thrombus resection, along with a thoracotomy with lung resection including the tumor emboli to one of the branches of the main pulmonary artery. Synchronous metastatic lesions were found on the liver in one case and contiguous extension of renal tumor to the pancreas in another. CONCLUSION: In patients with IVC thrombus with synchronous pulmonary artery tumor embolus, such as the cases presented in this series, a careful multidisciplinary management approach is preferable. Transplant technique used in our open approach minimizes complications, blood loss, and provides excellent visualization for abdominal vascular manipulation of IVC. This provides a potentially curable treatment option with acceptable survival rates.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Pulmonares/cirurgia , Artéria Pulmonar/cirurgia , Veia Cava Inferior/cirurgia , Adulto , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Nefrectomia/métodos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Veias Renais/diagnóstico por imagem , Veias Renais/patologia , Veias Renais/cirurgia , Trombose/diagnóstico por imagem , Trombose/patologia , Trombose/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/patologia , Trombose Venosa/cirurgia
7.
PLoS One ; 15(8): e0237308, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790691

RESUMO

The isolation and analysis of circulating tumor cells (CTC) has the potential to provide minimally invasive diagnostic, prognostic and predictive information. Widespread clinical implementation of CTC analysis has been hampered by a lack of comparative investigation between different analytic methodologies in clinically relevant settings. The objective of this study was to evaluate four different CTC isolation techniques-those that rely on surface antigen expression (EpCAM or CD45 using DynaBeads® or EasySep™ systems) or the biophysical properties (RosetteSep™ or ScreenCell®) of CTCs. These were evaluated using cultured cells in order to calculate isolation efficiency at various levels including; inter-assay and inter-operator variability, protocol complexity and turn-around time. All four techniques were adequate at levels above 100 cells/mL which is commonly used for the evaluation of new isolation techniques. Only the RosetteSep™ and ScreenCell® techniques were found to provide adequate sensitivity at a level of 10 cells/mL. These techniques were then applied to the isolation and analysis of circulating tumor cells blood drawn from metastatic breast cancer patients where CTCs were detected in 54% (15/28) of MBC patients using the RosetteSep™ and 75% (6/8) with ScreenCell®. Overall, the ScreenCell® method had better sensitivity.


Assuntos
Neoplasias da Mama/secundário , Separação Celular/métodos , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Molécula de Adesão da Célula Epitelial/análise , Feminino , Humanos , Antígenos Comuns de Leucócito/análise , Pessoa de Meia-Idade
8.
Mol Carcinog ; 59(10): 1129-1139, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822091

RESUMO

For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage of the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor cells (CTCs) and other peripheral blood mononuclear cells (PBMCs) may provide valuable prognostic information. The purpose of this study was to use single-cell RNA-sequencing (scRNA-seq) of liquid biopsies from breast cancer patients to begin defining intravascular interactions. We captured CTCs from the peripheral blood of breast cancer patients using size-exclusion membranes followed by scRNA-seq of enriched CTCs and carry-over PBMCs. Transcriptome analysis identified two populations of CTCs: one enriched for transcripts indicative of estrogen responsiveness and increased proliferation and another enriched for transcripts characteristic of reduced proliferation and epithelial-mesenchymal transition (EMT). We applied interactome and pathway analysis to determine interactions between CTCs and other captured cells. Our analysis predicted for enhanced immune evasion in the CTC population with EMT characteristics. In addition, PD-1/PD-L1 pathway activation and T cell exhaustion were predicted in T cells isolated from breast cancer patients compared with normal T cells. We conclude that scRNA-seq of breast cancer CTCs generally stratifies them into two types based on their proliferative and epithelial state and differential potential to interact with PBMCs. Better understanding of CTC subtypes and their intravascular interactions may help design treatments directed against CTCs with high metastatic and immune-evasive competence.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal , Leucócitos Mononucleares/patologia , Células Neoplásicas Circulantes/patologia , Neoplasias da Mama/sangue , Feminino , Humanos , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Células Tumorais Cultivadas
9.
PLoS One ; 15(8): e0237506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790768

RESUMO

Circulating tumor cells (CTCs) invade blood vessels in solid tumors and promote metastases by circulating in the blood. CTCs are thus recognized as targets for liquid biopsy and can provide useful information for design of treatments. This diagnostic approach must consider not only the number of CTCs but also their molecular and genetic characteristics. For this purpose, use of devices that enrich CTCs independent of these characteristics and detectors that recognize various CTC characteristics is essential. In the present study, we developed a CTC detection system comprising ClearCell FX and ImageStream Mark II. We clarified the analytical performance of this system by evaluating recovery rate, lower limits of detection, and linearity. These parameters are critical for detecting rare cells, such as CTCs. We tested these parameters using three cell lines with different expression levels of the epithelial marker-epithelial cell adhesion molecule (EpCAM) and spiked these cells into whole-blood samples from healthy donors. The average recovery rate and lower limit of detection were approximately 40% and five cells/7.5 mL of whole blood, respectively. High linearity was observed for all evaluated samples. We also evaluated the ability of the system to distinguish between normal and abnormal cells based on protein expression levels and gene amplification and found that the system can identify abnormal cells using these characteristics. The CTC detection system thus displays the ability to distinguish specific characteristics of CTC, thereby providing valuable information for cancer treatment.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Molécula de Adesão da Célula Epitelial/metabolismo , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Tumorais Cultivadas
10.
J Postgrad Med ; 66(3): 155-158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32675452

RESUMO

Pulmonary microvascular tumor embolism (PMTE), pulmonary tumor thrombotic microangiopathy (PTTM), and lymphangitis carcinomatosis (LC) have an intricate pathophysiology and usually occur with cancers of breast, stomach, and lung. Microvascular pulmonary metastases attributable to cervical cancer are a rarity. Clinical presentation and autopsy findings of patients with microvascular pulmonary metastases in cervical cancers were studied with a review of literature. Four patients (mean age of 55.5 years) with carcinoma cervix showed microvascular metastases. Three of whom presented with respiratory symptoms, and the fourth case was unresponsive on presentation. Each patient succumbed to their illness shortly after admission. Autopsy examination performed on each patient depicted varying combination of PMTE, PTTM, and LC, all with squamous histology. This case series highlights the rare association of carcinoma cervix with the aforementioned microvascular phenomena. Besides, it underscores the sequential mechanism of occurrence of microvascular pulmonary metastasis and the associated guarded prognosis.


Assuntos
Adenocarcinoma/secundário , Neoplasias Pulmonares/secundário , Pulmão/irrigação sanguínea , Células Neoplásicas Circulantes/patologia , Microangiopatias Trombóticas/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Autopsia , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Artéria Pulmonar/patologia , Microangiopatias Trombóticas/mortalidade , Neoplasias do Colo do Útero/mortalidade
11.
Medicine (Baltimore) ; 99(27): e20726, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629647

RESUMO

INTRODUCTION: Scleromyxedema (rare cutaneous mucinosis), is characterized by the formation of lichenoid papules and presence of Serum monoclonal IgG in most cases, or all; after repeated testing. PATIENT CONCERNS: The patient is a 51-year-old male presented with thick, disfiguring elephant-like erythematous skin folds over the forehead, papular shiny eruptions over ears and trunk and waxy erythematous papules over arms and hands without dysphagia or respiratory or neurologic symptoms DIAGNOSIS: : Skin biopsy from right arm was consistent with scleromyxedema. Serum cryoglobulin was reported negative. Complete blood count and routine blood biochemistry were normal. Thyroid function tests were normal. Serum protein electrophoresis and immunofixation showed monoclonal band of 14.5 g/L typed as IgG lambda. INTERVENTIONS: Our patient was refractory to lenalidomide however improved clinically on immunoglobulins infusions on monthly basis without change in the MGUS level. OUTCOMES: NGF analysis revealed approximately 0.25% Lambda monotypic plasma cells in the bone marrow expressing CD38, CD138, and CD27 with aberrant expression of CD56 and were negative for CD45, CD19, CD117, and CD81. We also detected 0.002% circulating plasma cells (PCs) in peripheral blood. CONCLUSION: The immunophenotype of circulating tumor cells (CTCs) remain close to the malignant PCs phenotype in the BM. Hence, we report NGF approach as a novel diagnostic tool for highly sensitive MRD detection in plasma cell dyscrasias including scleromyxedema.


Assuntos
Citometria de Fluxo/métodos , Células Neoplásicas Circulantes/patologia , Escleromixedema/patologia , Orelha Externa/patologia , Testa/patologia , Humanos , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Paraproteinemias/imunologia , Paraproteinemias/patologia , Escleromixedema/terapia , Pele/patologia
12.
Cardiovasc Pathol ; 49: 107244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32652483

RESUMO

Cardiac myxoma is a rare benign neoplasm of the heart. Historically myxomas were incidental findings during autopsies, however improved imaging techniques made these diagnosis possible in living patients, making the surgical treatment of these neoplasms achievable. Cardiac myxomas may occur both sporadically and in a familial context, often in the clinico-pathological picture of the Carney complex. While familial myxomas occur in the context of well-known genetic mutations, the molecular etiology of sporadically occurring myxomas is still not completely clear. We must note however that many of the patients affected by myxomas are asymptomatic; when symptoms are present they are often nonspecific and hard to decipher, especially when referring to sporadically occurring heart myxomas. In this paper we describe a case of sudden death from the massive embolization of a left atrial cardiac myxoma. We also reviewed all the cases in the literature of sudden death from heart myxoma embolism. An accurate epidemiology of heart myxomas would be the key to outline the best treatment practices and the etiology of sporadic myxomas, nevertheless this target could only be pursued with a deep revaluation of the clinical autopsy as a fundamental diagnostic tool.


Assuntos
Morte Súbita/etiologia , Embolia/etiologia , Neoplasias Cardíacas/complicações , Mixoma/complicações , Células Neoplásicas Circulantes/patologia , Adulto , Autopsia , Biópsia , Causas de Morte , Morte Súbita/patologia , Embolia/patologia , Evolução Fatal , Neoplasias Cardíacas/patologia , Humanos , Masculino , Mixoma/patologia
13.
Lancet Respir Med ; 8(7): 709-716, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32649919

RESUMO

BACKGROUND: Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Blood signatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classify undetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could be detected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosed radiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening. METHODS: We did a prospective, multicentre, cohort study in 21 French university centres. Participants had to be eligible for lung cancer screening as per National Lung Screening Trial criteria and have chronic obstructive pulmonary disease with a fixed airflow limitation defined as post-bronchodilator FEV1/FVC ratio of less than 0·7. Any cancer, other than basocellular skin carcinomas, detected within the previous 5 years was the main exclusion criterion. Participants had three screening rounds at 1-year intervals (T0 [baseline], T1, and T2), which involved LDCT, clinical examination, and a blood test for CTCs detection. Participants and investigators were masked to the results of CTC detection, and cytopathologists were masked to clinical and radiological findings. Our primary objective was to test the diagnostic performance of CTC detection using the ISET technique in lung cancer screening, compared with cancers diagnosed by final pathology, or follow up if pathology was unavailable as the gold standard. This study is registered with ClinicalTrials.gov identifier, number NCT02500693. FINDINGS: Between Oct 30, 2015, and Feb 2, 2017, we enrolled 614 participants, predominantly men (437 [71%]), aged 65·1 years (SD 6·5), and heavy smokers (52·7 pack-years [SD 21·5]). 81 (13%) participants dropped out between baseline and T1, and 56 (11%) did between T1 and T2. Nodules were detected on 178 (29%) of 614 baseline LDCTs. 19 participants (3%) were diagnosed with a prevalent lung cancer at T0 and 19 were diagnosed with incident lung cancer (15 (3%) of 533 at T1 and four (1%) of 477 at T2). Extrapulmonary cancers were diagnosed in 27 (4%) of participants. Overall 28 (2%) of 1187 blood samples were not analysable. At baseline, the sensitivity of CTC detection for lung cancer detection was 26·3% (95% CI 11·8-48·8). ISET was unable to predict lung cancer or extrapulmonary cancer development. INTERPRETATION: CTC detection using ISET is not suitable for lung cancer screening. FUNDING: French Government, Conseil Départemental 06, Fondation UNICE, Fondation Aveni, Fondation de France, Ligue Contre le Cancer-Comité des Alpes-Maritimes, ARC (Canc'Air Genexposomics), Claire de Divonne-Pollner, Enca Faidhi, Basil Faidhi, Fabienne Mourou, Michel Mourou, Leonid Fridlyand, cogs4cancer, and the Fondation Masikini.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico , Células Neoplásicas Circulantes/patologia , Idoso , Biomarcadores , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Prospectivos , Tomografia Computadorizada por Raios X
14.
Vasc Endovascular Surg ; 54(7): 565-572, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32677549

RESUMO

OBJECTIVES: To investigate the safety and efficacy of a stent combined with a linear strand of 125I seeds to treat malignant cancer-associated venous obstruction. METHODS: We retrospectively analyzed the data of 57 patients with malignant cancer-associated venous obstruction. Nineteen patients underwent the placement of a stent combined with a linear strand of 125I seeds (group A), and 38 patients underwent the placement of a bare stent (group B). The following parameters were compared between the 2 groups of patients: symptom relief rate, duration of venous patency, survival time, quality of life, and adverse events. RESULTS: A total of 34 stents and 527 seeds were implanted in group A, while a total of 57 stents were implanted in group B. The surgery success rate was 96.5%, and no serious complication related to the surgery was reported. Symptoms of venous obstruction improved significantly after surgery. The score of group A decreased from 14.74 ± 0.562 points before surgery to 2.79 ± 1.357 points after surgery(P < .001), and the score of group B decreased from 13.79 ± 1.398 points before surgery to 5.55 ± 3.674 points after surgery (P < .001). The patency rate of group A was significantly higher than that of group B at 1 to 6 months after surgery (100%, 84.2%, 68.4%, 63.2%, 36.8%, 21.1% vs 68.4%, 23.7%, 18.4%, 7.9%, 5.3%, 2.6%, respectively; P < .05). Before treatment, there was no statistically significant difference in the Karnofsky Performance Status (KPS) score between the groups (P = .791). After 1 to 6 months of treatment, the KPS score was significantly higher in group A than in group B (P = .013). The median patency duration in groups A and B was 125 days (95% CI: 80.018-169.982) and 35 days (95% CI: 20.501-49.499), respectively (P < .001). The median survival time of group A was 155 days (95% CI: 110.406-199.594), and that of group B was 98 days (95% CI: 55.712-140.288; P = .325). Multivariate analysis showed that the implantation of a stent combined with a linear strand of 125I seeds and the KPS score (≥80 points) were independent factors of long-term patency after stent placement. CONCLUSIONS: The placement of a stent combined with a linear strand of 125I seeds is a safe and effective treatment for venous obstruction caused by malignant tumors. This treatment provides prolonged patency compared with the placement of bare stent, and while it does not significantly improve the survival time of patients, it can improve their quality of life.


Assuntos
Procedimentos Endovasculares/instrumentação , Radioisótopos do Iodo/administração & dosagem , Neoplasias/terapia , Células Neoplásicas Circulantes/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Stents , Doenças Vasculares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/mortalidade , Neoplasias/patologia , Desenho de Prótese , Qualidade de Vida , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/etiologia , Doenças Vasculares/mortalidade , Doenças Vasculares/patologia , Grau de Desobstrução Vascular
15.
J Cancer Res Clin Oncol ; 146(10): 2621-2630, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32661602

RESUMO

PURPOSE: The epithelial-to-mesenchymal transition (EMT) phenotype-based subsets of circulating tumor cells (CTCs) might be predictors of tumor progression. We evaluated the clinical properties of different phenotypic CTCs in patients with non-small cell lung cancer (NSCLC). Secondly, we explored the association between different phenotypic CTCs and the uptake of 18F-fluorodeoxyglucose (FDG) by the primary tumor on a positron emission tomographic (PET) scan. METHODS: Venous blood samples from 34 pathologically confirmed Stage IIB-IVB NSCLC patients were collected prospectively. CTCs were immunoassayed using a SE-i·FISH®CTC kit. We identified CTCs into cytokeratin positive (CK+) and cytokeratin negative (CK-) phenotypes. CTC classifications were correlated with the maximum standardized uptake value (SUVmax) measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Overall survival (OS) and progression-free survival (PFS) curves were produced using the Kaplan-Meier method. RESULTS: CTCs were detected in 91.2% of NSCLC patients. CTC counting was associated with TNM stage (P = 0.014) and distant metastasis (P = 0.007). The number of CK-CTCs was also positively associated with TNM stage (P = 0.022) and distant metastasis (P = 0.007). Both total CTC counting and CK-CTC counting did not show association with SUVmax value (P = 0.959, P = 0.903). Kaplan-Meier survival analysis demonstrated that patients with ≥ 7 CTCs had shorter OS (P = 0.003) and PFS (P = 0.001) relative to patients with < 7 CTCs). Notably, the number of CK-CTCs can act as independent risk factors for PFS (P = 0.044) and OS (P = 0.043) in NSCLC patients. However, SUVmax value was not associated with OS (P = 0.895) and PFS (P = 0.686). CONCLUSION: The CTC subpopulations could be useful evidence for testing metastasis and prognosis in NSCLC patients. The SUVmax value of the primary tumor was not related to prognosis in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Fenótipo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
16.
Anticancer Res ; 40(6): 3435-3444, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487642

RESUMO

BACKGROUND/AIM: Although it has been suggested that circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) might be used in a complementary manner in lung cancer diagnosis, limited confirmatory data are available. In this prospective study, we evaluated the diagnostic performance of each assay separately and in combination. PATIENTS AND METHODS: From March 2018 to January 2019, patients with suspected primary lung cancer, who underwent routine lung cancer work-up and peripheral blood sampling, were prospectively enrolled in the study. Epithelial cell adhesion molecule and cytokeratin served as markers of CTCs. In terms of ctDNA analysis, single-nucleotide variants were evaluated via next-generation sequencing. RESULTS: We analyzed 111 patients, including 99 with primary lung cancer and 12 with benign pulmonary disease. The median number of CTCs in 10 ml of blood was 3. The most frequently detected single nucleotide variants of ctDNA were TP53, CDKN2A, and EGFR. The diagnostic sensitivity of conventional tumor marker (combination of carcinoembryonic antigen/CYFRA 21-1/neuron-specific enolase) was 66.7%, while those of the ctDNA and CTC assays were 72.7% and 65.7%, respectively. The sensitivity of the CTC/ctDNA combination (95.0%) was significantly greater than those of the CTC (p<0.001), ctDNA (p<0.001), or conventional tumor marker (p<0.001) alone. Subgroup analysis revealed that the sensitivity of the combination assay was greater than those of the CTC or ctDNA assays alone, regardless of tumor stage or histopathology type. CONCLUSION: The CTC/ctDNA combination assay enhanced the sensitivity of primary lung cancer diagnosis. The combination assay strategy may be clinically useful and could enhance the early detection of lung cancer (ClinicalTrials.gov number: NCT03479099).


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , DNA de Neoplasias , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Células Neoplásicas Circulantes/patologia , Idoso , Idoso de 80 Anos ou mais , DNA de Neoplasias/sangue , Suscetibilidade a Doenças , Feminino , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único
17.
Anticancer Res ; 40(6): 3559-3564, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487658

RESUMO

BACKGROUND/AIM: We aimed to elucidate the clinical implication of the epithelial-mesenchymal plasticity of circulating tumor cells (CTCs) in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: CTCs isolated from 44 patients with non-recurrent/metastatic HNSCC and 42 with recurrent/metastatic (R/M) HNSCC were classified into four epithelial-mesenchymal transition (EMT) statuses based on the expression of epithelial (keratin 19) and mesenchymal (vimentin) markers and the relationships between EMT status in CTCs and clinical factors were investigated. RESULTS: E+M- CTC phenotype was more frequent in patients without recurrence/metastasis (p=0.0468) and was also more frequent in those with a complete response (p=0.0346). The E+M+ phenotype constituted the major proportion of the CTCs detected in patients with R/M HNSCC (p=0.0374). CONCLUSION: CTCs may play unique roles at various stages of metastasis through transitioning from epithelial to mesenchymal phenotypes.


Assuntos
Transição Epitelial-Mesenquimal , Células Neoplásicas Circulantes/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Biomarcadores Tumorais , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Masculino , Recidiva Local de Neoplasia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade
18.
Nat Protoc ; 15(7): 2163-2185, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32572244

RESUMO

Circulating tumor cells (CTCs) enable noninvasive liquid biopsy and identification of cancer. Various approaches exist for the capture and release of CTCs, including microfluidic methods and those involving magnetic beads or nanostructured solid interfaces. However, the concomitant cell damage and fragmentation that often occur during capture make it difficult to extensively characterize and analyze living CTCs. Here, we describe an aptamer-trigger-clamped hybridization chain reaction (atcHCR) method for the capture of CTCs by porous 3D DNA hydrogels. The 3D environment of the DNA networks minimizes cell damage, and the CTCs can subsequently be released for live-cell analysis. In this protocol, initiator DNAs with aptamer-toehold biblocks specifically bind to the epithelial cell adhesion molecule (EpCAM) on the surface of CTCs, which triggers the atcHCR and the formation of a DNA hydrogel. The DNA hydrogel cloaks the CTCs, facilitating quantification with minimal cell damage. This method can be used to quantitively identify as few as 10 MCF-7 cells in a 2-µL blood sample. Decloaking of tumor cells via gentle chemical stimulus (ATP) is used to release living tumor cells for subsequent cell culture and live-cell analysis. We also describe how to use the protocol to encapsulate and release cells of cancer cell lines, which can be used in preliminary experiments to model CTCs. The whole protocol takes ~2.5 d to complete, including downstream cell culture and analysis.


Assuntos
Separação Celular/métodos , DNA/química , Hidrogéis/química , Células Neoplásicas Circulantes/patologia , Cápsulas , Sobrevivência Celular , Humanos , Células MCF-7 , Hibridização de Ácido Nucleico
19.
Medicine (Baltimore) ; 99(22): e20615, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481476

RESUMO

The aim of the study was to evaluate the potential role of circulating tumor cell (CTC) detection in the surgical assessment of renal cell carcinoma (RCC) patients with thrombi.Nine patients diagnosed with renal mass and thrombi were enrolled from June 2018 to January 2019. Blood samples were collected for CTC detection using SE-iFISH assay. CD45, DAPI, programmed death ligand 1, and fluorescence in situ hybridization with the centromere of chromosome 8 (CEP8) were immune-stained for analysis. Patient demographics, clinical features, pathological characteristics, and CTC detection results were extracted for analysis.Seven of 9 patients (77.8%) had 12 detectable CTCs, 5 of which were with CEP8-positive signal ≥5 and the others were CEP8-positive signal = 3. All 3 patients (100%) with IVC invasion had detectable CTCs, whereas CTCs were detected in 4 of 6 patients (66.7%) without IVC invasion. CEP8 analysis revealed that CTCs in IVC invasion patients were all of CEP8-positive signal ≥5 status, whereas only half of the CTCs in patients without IVC invasion were of CEP8-positive signal ≥5 pattern.In conclusion, both CTC subtype and total CTC number may serve as a marker for predicting inferior vena cava invasion in RCC patients.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Invasividade Neoplásica/patologia , Células Neoplásicas Circulantes/patologia , Trombose/patologia , Veia Cava Inferior/patologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Cancer Res Clin Oncol ; 146(8): 2051-2066, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32462295

RESUMO

PURPOSE: To explore whether targeted next generation sequencing (NGS) of liquid biopsy in advanced non-small cell lung cancer (NSCLC) could potentially overcome the innate problems that arise with standard tissue biopsy, like intratumoral heterogeneity and the inability to obtain adequate samples for analysis. METHODS: The Scopus, Cochrane Library, and MEDLINE (via PubMed) databases were searched for studies with matched tissue and liquid biopsies from advanced NSCLC patients, analyzed with targeted NGS. The number of mutations detected in tissue biopsy only, liquid biopsy only, or both was assessed and the positive percent agreement (PPA) of the two methods was calculated for every clinically relevant gene. RESULTS: A total of 644 unique relevant articles were retrieved and data were extracted from 38 studies fulfilling the inclusion criteria. The sample size was composed of 2000 mutations tested in matched tissue and liquid biopsies derived from 1141 patients. No studies analyzed circulating tumor cells. The calculated PPA rates were 53.6% (45/84) for ALK, 53.9% (14/26) for BRAF, 56.5% (13/23) for ERBB2, 67.8% (428/631) for EGFR, 64.2% (122/190) for KRAS, 58.6% (17/29) for MET, 54.6% (12/22) for RET, and 53.3% (8/15) for ROS1. We additionally recorded data for 65 genes that are not recommended by current guidelines for mutational testing. An extra category containing results of unspecified genes was added, with a PPA rate of 55.7% (122/219). CONCLUSION: Despite many advantages, liquid biopsy might be unable to fully substitute its tissue counterpart in detecting clinically relevant mutations in advanced NSCLC patients. However, it may serve as a helpful tool when making therapeutic decisions. More studies are needed to evaluate its role in everyday clinical practice.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Biópsia/métodos , Carcinoma Pulmonar de Células não Pequenas/sangue , DNA Tumoral Circulante/genética , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Biópsia Líquida/métodos , Neoplasias Pulmonares/sangue , Células Neoplásicas Circulantes/patologia
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