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1.
Medicine (Baltimore) ; 100(5): e24292, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592873

RESUMO

RATIONALE: Gefitinib is a first-line palliative chemotherapy drug used to treat advanced non-small-cell lung cancer (NSCLC) in patients who have an epidermal growth factor receptor (EGFR) mutation. However, approximately two-thirds of NSCLC patients with EGFR-tyrosine kinase inhibitor experience dermatological toxicity. Cutaneous toxicity is usually not life threatening but can necessitate modification or discontinuation of medication in severe cases. In this case, despite a reduction in the dose of gefitinib due to side effects, combined treatment with modified Bojungikki-tang (BJKIT) increased progression-free survival (PFS) in an advanced NSCLC patient. PATIENT CONCERNS: An 83-year-old Asian woman presented with chief complaints of chronic cough, dyspnea, weight loss, and anorexia. DIAGNOSES: The patient was diagnosed with stage IV NSCLC (T2aN3M1), adenocarcinoma with metastasis to the lymph node, brain, and bone based on image scan and biopsy. An EGFR deletion was detected in exon 19. INTERVENTIONS: The patient was treated with gefitinib (250 mg/d) and traditional herbal medicine, modified Bojungikki-tang (BJIKT). However, after 1 year of combination therapy, gefitinib was tapered down to once per week while modified BJIKT was maintained. OUTCOMES: A partial response was achieved, but after 3 months severe papulopustular skin rashes developed and became aggravated with time. Thus, the gefitinib dose was reduced. However, the PFS has been maintained for approximately 78 months. LESSONS: Despite the reduction in gefitinib dose due to side effects, the combined treatment of gefitinib and the modified BJIKT has maintained a PFS of over 78 months, indicating that modified BJIKT enhanced the anti-cancer effect of gefitinib in a patient with advanced NSCLC harboring the EFGR mutation, and may have delayed acquired resistance, the main limitation on the efficacy of gefitinib. Further investigations including clinical trials are needed to confirm these effects.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB/genética , Gefitinibe , Neoplasias Pulmonares , Fitoterapia/métodos , Dermatopatias , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Gefitinibe/administração & dosagem , Gefitinibe/efeitos adversos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Mutação , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Dermatopatias/induzido quimicamente , Dermatopatias/diagnóstico , Dermatopatias/prevenção & controle
2.
Nat Commun ; 11(1): 5127, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046716

RESUMO

Despite the importance of AKT overactivation in tumor progression, results from clinical trials of various AKT inhibitors remain suboptimal, suggesting that AKT-driven tumor metastasis needs to be further understood. Herein, based on long non-coding RNA (lncRNA) profiling induced by active AKT, we identify that VAL (Vimentin associated lncRNA, LINC01546), which is directly induced by AKT/STAT3 signaling, functions as a potent pro-metastatic molecule and is essential for active AKT-induced tumor invasion, metastasis and anoikis resistance in lung adenocarcinoma (LAD). Impressively, chemosynthetic siRNAs against VAL shows great therapeutic potential in AKT overactivation-driven metastasis. Interestingly, similar to activated AKT in LAD cells, although unable to induce epithelial-mesenchymal transition (EMT), VAL exerts potent pro-invasive and pro-metastatic effects through directly binding to Vimentin and competitively abrogating Trim16-depedent Vimentin polyubiquitination and degradation. Taken together, our study provides an interesting demonstration of a lncRNA-mediated mechanism for active AKT-driven EMT-independent LAD metastasis and indicates the great potential of targeting VAL or Vimentin stability as a therapeutic approach.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Vimentina/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/fisiopatologia , Animais , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Camundongos , Metástase Neoplásica , Proteólise , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Vimentina/genética
3.
BMJ Case Rep ; 13(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028572

RESUMO

A 13-year-old boy presented to hospital with 3-day self-limited fever, followed by dry cough, persistent asthenia and impaired general condition of 2 weeks' duration. Blood analyses showed a severe inflammatory status and chest X-ray images were consistent with bilateral COVID-19 pneumonia. He developed an acute respiratory failure that required paediatric intensive care admission and non-invasive ventilation. A targeted COVID-19 treatment was initiated with hydroxicloroquine, corticosteroids, enoxaparine and a single dose of tocilizumab. Repeated serological tests and real-time reverse transcription PCR for SARS-CoV-2 were negative. Other infectious pathogens were also ruled out. Thoracic high resolution CT showed an intense bilateral pulmonary dissemination with lytic vertebral bone lesions. After diagnostic investigations, Ewing's sarcoma with metastatic pulmonary dissemination was diagnosed. Nowadays, in the context of SARS-CoV-2 community pandemic, we cannot forget that COVID-19 clinical presentation is not specific and other entities can mimic its clinical features.


Assuntos
Infecções por Coronavirus/diagnóstico , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumonia Viral/diagnóstico , Sarcoma de Ewing , Tomografia Computadorizada por Raios X/métodos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Exame de Medula Óssea/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/secundário , Masculino , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos
4.
J Cancer Res Ther ; 16(4): 788-792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930119

RESUMO

Context: Spirometry is an important tool to monitor treatment response in diseases such as chronic obstructive pulmonary disease and asthma. However, there is lack of evidence to support its application to evaluate response to chemotherapy in advanced lung cancer. It might be a useful adjunct to the imaging-based response evaluation which lacks functional assessment of lungs. Aims: The study was conducted to evaluate the change in spirometry in lung cancer patients after chemotherapy and to find its correlation with change in physical tumor size. Subjects and Methods: Sixty-two advanced lung cancer patients who were eligible for palliative chemotherapy were enrolled. Baseline tumor size evaluation using Response Evaluation Criteria in Solid Tumor (RECIST)-based scoring system, and spirometry was done. Four cycles of double agent (platinum doublets) chemotherapy were administered, after which treatment response was evaluated. Repeat spirometry was analyzed and correlated with changes in physical tumor size. Results: Twenty-five patients showed a response (all partial response) to four cycles of chemotherapy. Small cell carcinoma showed a better response rate than non-small cell carcinoma (78% vs. 39%). There was statistically significant improvement in forced expiratory volume in 1 (FEV1) (P = 0.01) and forced vital capacity (P = 0.03) in responders as compared to nonresponders. Change in FEV1 showed a statistically significant correlation with the change in tumor size (RECIST score) (r = -0.34; P = 0.04). Conclusions: Improvement in spirometry correlates with the tumor response as judged using RECIST criteria after chemotherapy. Further studies with bigger sample size are required to consolidate the results.


Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Estudos Prospectivos , Testes de Função Respiratória/métodos , Espirometria/métodos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
5.
Nat Commun ; 11(1): 4878, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985499

RESUMO

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here, we perform multi-omics analysis of 56 PSC samples, 14 of which are microdissected to analyze intratumoral heterogeneity. We report the mutational landscape of PSC. The epithelial and sarcomatoid components share numerous genomic alterations, indicating a common progenitor. We find that epithelial-mesenchymal transition (EMT) plays important roles in the carcinogenesis of PSC. The pan-cancer analysis reveals high tumor mutation burden and leukocyte fraction of PSC. Integrated molecular classification shows three subgroups with distinct biology, prognosis and potential therapeutic strategies. Actionable mutations are enriched in C1 and C2, patients in C3 have a significantly longer overall survival, and C1 and C2 exhibit T-cell inflamed microenvironments. The three subgroups show molecular similarities to specific subtypes of conventional lung cancer. In conclusion, our study reveals the molecular characteristics and provides entry points for the treatment of PSC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Metilação de DNA , Transição Epitelial-Mesenquimal , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatologia , Mutação , Microambiente Tumoral
6.
Asian Cardiovasc Thorac Ann ; 28(9): 592-597, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32915659

RESUMO

OBJECTIVE: To assess whether preoperative incentive spirometer training would influence the development of postoperative pulmonary complications after lung resection. METHODS: Sixty-two lung resection patients were prospectively investigated; 17 were given an incentive spirometer preoperatively and 45 did not have an incentive spirometer preoperatively. Postoperatively, both arms exercised with an incentive spirometer. The number of repetitions per day, balls raised per repetition, correct technique of exercising, and postoperative pulmonary complications were compared between the 2 groups. Univariate binary logistic regression analysis of potential predictors of postoperative pulmonary complications led to multivariate analysis of independent predictors. Receiver operating characteristic analysis established the cutoff points of predictors. RESULTS: The group with no preoperative incentive spirometer developed more postoperative pulmonary complications than the preoperative incentive spirometer group (24.4% vs. 5.9%, respectively, p = 0.045). The preoperative incentive spirometer arm achieved more repetitions per day, balls per repetition, and correct incentive spirometer technique (p = 0.002, p < 0.001, p = 0.034, respectively). Balls raised per repetition and repetitions per day postoperatively were identified as independent predictors of postoperative pulmonary complications (p = 0.032 and p = 0.021, respectively). Less than 5 repetitions per day (sensitivity 93%, specificity 77%, p < 0.001) and less than 2 balls per repetition (sensitivity 93%, specificity 77%, p < 0.001) were predictive of postoperative pulmonary complications. CONCLUSION: Preoperative incentive spirometer exposure ensured better compliance with postoperative treatment and a more accurate technique (balls raised per repetition, repetitions per day). These variables correlated with a lower postoperative pulmonary complication rate.


Assuntos
Terapia por Exercício , Pneumopatias/prevenção & controle , Neoplasias Pulmonares/cirurgia , Educação de Pacientes como Assunto , Pneumonectomia/efeitos adversos , Cuidados Pré-Operatórios , Espirometria , Idoso , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/instrumentação , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Espirometria/instrumentação , Fatores de Tempo , Resultado do Tratamento
7.
Thorac Cancer ; 11(10): 2983-2986, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32790028

RESUMO

The current coronavirus disease 2019 (COVID-19) pandemic is associated with a heavy burden on the mental and physical health of patients, regional healthcare resources, and global economic activity. Many patients with lung cancer are thought to be affected by this situation. Therefore, in this study, we aimed to evaluate the impact of COVID-19 pandemic on lung cancer treatment scheduling. We retrospectively reviewed the medical records of lung cancer patients who were undergoing anticancer treatment at the National Hospital Organization Kyoto Medical Center (600 beds) in Kyoto, Japan, between 1 March 2020 and 31 May 2020. After the medical records were reviewed, the patients were assigned to one of two groups, depending on whether their lung cancer treatment schedule was delayed. We assessed the characteristics, types of histopathology and treatment, and the reason for the delay. A total 15 (9.1%) patients experienced a delay in lung cancer treatment during the COVID-19 pandemic. Patients with a treatment delay received significantly more immune checkpoint inhibitor (ICI) monotherapy than patients without a treatment delay (P = 0.0057). On the contrary, no patients receiving molecular targeted agents experienced a treatment delay during the COVID-19 pandemic period (P = 0.0027). The treatments of most of the patients were delayed at their request. We determined that 9.1% lung cancer patients suffered anxiety and requested a treatment delay during the COVID-19 pandemic. Oncologists should bear in mind that patients with cancer have more anxiety than expected under unprecedented circumstances such as the COVID-19 pandemic.


Assuntos
Ansiedade/psicologia , Infecções por Coronavirus/psicologia , Neoplasias Pulmonares/psicologia , Pneumonia Viral/psicologia , Tempo para o Tratamento , Idoso , Idoso de 80 Anos ou mais , Ansiedade/fisiopatologia , Betacoronavirus/patogenicidade , Protocolos Clínicos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Japão , Pulmão/fisiopatologia , Pulmão/virologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/virologia , Masculino , Registros Médicos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Estudos Retrospectivos
8.
Oncology ; 98(11): 771-778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32829332

RESUMO

INTRODUCTION: Because of the increasing age of the general population, there is an increasing number of older patients with lung cancer. Cancer chemotherapy often causes severe hematological toxicity in older patients. OBJECTIVE: This study aimed to explore the risk factors affecting the hematological toxicity of cytotoxic anticancer drugs in patients with lung cancer. METHODS: Data were retrospectively collected from 194 patients with lung cancer at Niigata University Medical and Dental Hospital, Japan, between April 2011 and March 2016, when the patients underwent their first round of cytotoxic chemotherapy. The patients were divided into three groups on the basis of age: <65, 65-74, and ≥75 years. Physiological functions and laboratory data before treatment, as well as hematological adverse events following chemotherapy, were compared among the groups. RESULTS: Patients aged ≥75 years were significantly more likely to experience grade 3 or 4 neutropenia, compared with patients aged <65 years. However, there were no differences in the incidence of anemia or thrombocytopenia among the age groups. The frequency of febrile neutropenia tended to increase with age. Multivariate analysis showed that age ≥75 years, male sex, and a performance status of ≥2 were independent factors for grade 3 or 4 neutropenia. Patients with 2 or 3 of these factors had a significantly higher frequency of neutropenia, compared with patients who had 0 or 1 of these factors. CONCLUSION: We found that age ≥75 years, male sex, and a performance status of ≥2 were independent risk factors for grade 3 or 4 neutropenia.


Assuntos
Doenças Hematológicas/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Fatores Etários , Idoso , Anemia/induzido quimicamente , Neutropenia Febril/induzido quimicamente , Feminino , Doenças Hematológicas/fisiopatologia , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente
10.
Artigo em Inglês | MEDLINE | ID: mdl-32633902

RESUMO

Malignant pleural mesothelioma is a disease of the pleural cavity that is strongly associated with asbestos exposure. In most cases it carries a poor prognosis. Patients often present with respiratory symptoms, caused by pleural effusion. Treatment, preferably in a multimodal setting, cannot provide cure, but can prolong survival and improve quality of life in selected cases.  Prior to eventual cytoreductive surgery, surgical intervention can provide histopathological proof of disease, and symptoms can be controlled with talc pleurodesis.  We present the case of a 67-year-old patient with malignant pleural mesothelioma who underwent video-assisted thoracoscopic biopsy and talc pleurodesis, and demonstrate our technique with a video tutorial showing how we performed the procedure.


Assuntos
Biópsia Guiada por Imagem/métodos , Neoplasias Pulmonares , Mesotelioma , Pleurodese/métodos , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patologia , Mesotelioma/fisiopatologia , Mesotelioma/terapia , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/prevenção & controle
11.
Am J Respir Crit Care Med ; 202(6): 843-852, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32437637

RESUMO

Rationale: Pulmonary hypertension (PH) associated with neurofibromatosis type 1 (NF1) is a rare and largely unknown complication of NF1.Objectives: To describe characteristics and outcomes of PH-NF1.Methods: We reported the clinical, functional, radiologic, histologic, and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs, and transplant-free survival of patients with PH-NF1 from the French PH registry.Measurements and Main Results: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median (minimum-maximum) age at diagnosis of 62 (18-82) years. At diagnosis, 92% were in New York Heart Association functional class III or IV. The 6-minute-walk distance was 211 (0-460) m. Pulmonary function tests showed low DlCO (30% [12-79%]) and severe hypoxemia (PaO2 56 [38-99] mm Hg). Right heart catheterization showed severe precapillary PH with a mean pulmonary artery pressure of 45 (10) mm Hg and a pulmonary vascular resistance of 10.7 (4.2) Wood units. High-resolution computed tomography images revealed cysts (76%), ground-glass opacities (73%), emphysema (49%), and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, and four patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling.Conclusions: PH-NF1 is characterized by a female predominance, a low DlCO, and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgia , Neoplasias Pulmonares/fisiopatologia , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Neurofibromina 1/genética , Adolescente , Adulto , Feminino , França , Humanos , Hipertensão Pulmonar/etiologia , Transplante de Pulmão/métodos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Adulto Jovem
12.
Postgrad Med ; 132(6): 568-571, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32400251

RESUMO

Introduction: The treatment for locally advanced squamous non-small cell lung cancer is still challenging. Drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) is a novel drug delivery and embolization system for lung cancer that has the potential to improve outcomes and reduce the incidence of adverse events (AEs). It is very rare to administer DEB-BACE as neoadjuvant therapy for lung cancer and achieve pathological complete response (pCR). Body: A 69-year-old male was hospitalized because of cough and hemoptysis caused by locally advanced squamous non-small cell lung cancer. According to his choice, he received DEB-BACE treatment without obvious AEs. After the DEB-BACE treatment, the pulmonary lesion was controlled and lobectomy was performed. Postoperative pathology showed pCR. The patient has recovered well. Conclusion: This was the first case of DEB-BACE as a neoadjuvant therapy and achieved pCR for lung cancer. DEB-BACE might be a new neoadjuvant therapy option for locally advanced non-small cell lung cancer, especially for squamous cell cancer.


Assuntos
Artérias Brônquicas , Carcinoma Pulmonar de Células não Pequenas , Quimioembolização Terapêutica/métodos , Hemoptise , Neoplasias Pulmonares , Pulmão , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Sistemas de Liberação de Medicamentos/métodos , Hemoptise/etiologia , Hemoptise/terapia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Masculino , Terapia Neoadjuvante/métodos , Pneumonectomia/métodos , Cuidados Pré-Operatórios/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
13.
Artigo em Inglês | MEDLINE | ID: mdl-32459074

RESUMO

In recent years, parenchymal sparing techniques for tumor resection have been developed in order to reduce the amount of lung parenchyma that must be removed in cases of centrally located tumors. These techniques maintain oncological radicality while reducing postoperative complications. At the same time, video-assisted thoracoscopic surgery (VATS) has been shown to offer comparable surgical and oncological outcomes to thoracotomy, even in complex cases that require tracheal and bronchial reconstructions. In this video tutorial, we describe a case of an isolated sleeve resection of the bronchus intermedius performed through a VATS approach for a bronchial paraganglioma.


Assuntos
Brônquios , Neoplasias Pulmonares , Paraganglioma , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Toracotomia/métodos , Adulto , Brônquios/diagnóstico por imagem , Brônquios/patologia , Brônquios/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Paraganglioma/patologia , Paraganglioma/fisiopatologia , Paraganglioma/cirurgia , Resultado do Tratamento
14.
Am J Respir Crit Care Med ; 202(2): 241-249, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32326730

RESUMO

Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.Objectives: To develop and validate a deep learning method to improve the management of IPNs.Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions.Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4-90.7%) and 91.9% (95% CI, 88.7-94.7%), compared with 78.1% (95% CI, 68.7-86.4%) and 81.9 (95% CI, 76.1-87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts.Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Humanos , Neoplasias Pulmonares/epidemiologia , Redes Neurais de Computação , Estados Unidos/epidemiologia
15.
Sheng Wu Gong Cheng Xue Bao ; 36(4): 740-749, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32347068

RESUMO

Immune cell infiltration is of great significance for the diagnosis and prognosis of cancer. In this study, we collected gene expression data of non-small cell lung cancer (NSCLC) and normal tissues included in TCGA database, obtained the proportion of 22 immune cells by CIBERSORT tool, and then evaluated the infiltration of immune cells. Subsequently, based on the proportion of 22 immune cells, a classification model of NSCLC tissues and normal tissues was constructed using machine learning methods. The AUC, sensitivity and specificity of classification model built by random forest algorithm reached 0.987, 0.98 and 0.84, respectively. In addition, the AUC, sensitivity and specificity of classification model of lung adenocarcinoma and lung squamous carcinoma tissues constructed by random forest method 0.827, 0.75 and 0.77, respectively. Finally, we constructed a prognosis model of NSCLC by combining the immunocyte score composed of 8 strongly correlated features of 22 immunocyte features screened by LASSO regression with clinical features. After evaluation and verification, C-index reached 0.71 and the calibration curves of three years and five years were well fitted in the prognosis model, which could accurately predict the degree of prognostic risk. This study aims to provide a new strategy for the diagnosis and prognosis of NSCLC based on the classification model and prognosis model established by immune cell infiltration.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatologia , Aprendizado de Máquina , Prognóstico
16.
AJR Am J Roentgenol ; 214(6): 1269-1279, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32255690

RESUMO

OBJECTIVE. The purpose of this study is to establish whether texture analysis and densitometry are complementary quantitative measures of chronic obstructive pulmonary disease (COPD) in a lung cancer screening setting. MATERIALS AND METHODS. This was a retrospective study of data collected prospectively (in 2004-2010) in the Danish Lung Cancer Screening Trial. The texture score, relative area of emphysema, and percentile density were computed for 1915 baseline low-dose lung CT scans and were evaluated, both individually and in combination, for associations with lung function (i.e., forced expiratory volume in 1 second as a percentage of predicted normal [FEV1% predicted]), diagnosis of mild to severe COPD, and prediction of a rapid decline in lung function. Multivariate linear regression models with lung function as the outcome were compared using the likelihood ratio test or the Vuong test, and AUC values for diagnostic and prognostic capabilities were compared using the DeLong test. RESULTS. Texture showed a significantly stronger association with lung function (p < 0.001 vs densitometric measures), a significantly higher diagnostic AUC value (for COPD, 0.696; for Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 1, 0.648; for GOLD grade 2, 0.768; and for GOLD grade 3, 0.944; p < 0.001 vs densitometric measures), and a higher but not significantly different association with lung function decline. In addition, only texture could predict a rapid decline in lung function (AUC value, 0.538; p < 0.05 vs random guessing). The combination of texture and both densitometric measures strengthened the association with lung function and decline in lung function (p < 0.001 and p < 0.05, respectively, vs texture) but did not improve diagnostic or prognostic performance. CONCLUSION. The present study highlights texture as a promising quantitative CT measure of COPD to use alongside, or even instead of, densitometric measures. Moreover, texture may allow early detection of COPD in subjects who undergo lung cancer screening.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Dinamarca , Densitometria , Feminino , Humanos , Neoplasias Pulmonares/fisiopatologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória , Estudos Retrospectivos
17.
Zhonghua Zhong Liu Za Zhi ; 42(3): 216-221, 2020 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-32252200

RESUMO

Objective: To investigate the effect of compound matrine injection on morphine tolerance in mice with lung cancer in situ and the expressions of multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp). Methods: A mouse model of lung cancer in situ and morphine tolerance mode was established. The mice were injected with gradient concentration of compound matrine. The pain thresholds under different conditions were measured by thermal radiation tail-flick method. The mRNA level of MDR1 was tested by reverse transcription polymerase chain reaction (RT-PCR) and the protein level of P-gp was detected by western blot. The DNA binding activity of cyclophosphoadenosine response element binding protein (CREB) to the promoter of MDR1 gene was detected by electrophoretic mobility shift assay (EMSA). Results: The maximum analgesic percentage (MPE) of the mice in the morphine group was (85.21±6.53)% on the 8th day, and decreased to (38.45±5.52)% and (28.14±4.52)% on the 10th and 12th day, respectively, which indicated the morphine tolerance of mice with lung cancer in situ.The MPE of the mice in the group treated with morphine and compound matrine injection (300 mg/kg) was (79.34±6.50)% on the 8th day, and decreased to (62.16±5.53)% and (40.20±4.50)% on the 10th and 12th day, respectively.The results of RT-PCR assay showed that the relative expression levels of MDR1 mRNA in the brain tissues of mice in the morphine group, saline group, morphine combined with compound matrine injection (300 mg/kg) group and compound matrine injection (200 mg/kg) group were 2.33±0.79, 1.04±0.38, 1.37±0.38, and 1.43±0.53, respectively. There were statistically significant differences between the morphine group and the normal saline group, the morphine group and the morphine combined with compound matrine injection (300 mg/kg) group (P<0.05). There was no significant difference between the normal saline group and the compound matrine injection (200 mg/kg) group (P=0.05). The results of western blot showed that the relative expression levels of P-gp protein in the brain tissue of mice in the morphine group, saline group, and morphine combined with compound matrine injection (300 mg/kg) group were 1.86±0.40, 1.00±0.23, and 1.27±0.27, respectively. The expression of P-gp protein in the morphine group was significantly higher than those of the normal saline group and the morphine combined with compound matrine injection (300 mg/kg) group (P<0.05). The DNA-binding activity of CREB in the saline group was (0.23±0.07) Pu, significantly lower than (0.89±0.23) Pu of morphine combined with naloxone group and (0.80±0.23) Pu of morphine group (P<0.05). While the CREB DNA binding activity of morphine combined with compound matrine injection (300 mg/kg) group was (0.79±0.21) Pu, implicated that compound matrine had marginal effect on the DNA-binding activity of CREB (P>0.05). Conclusion: Compound matrine injection can significantly improve morphine tolerance and drug resistance of lung cancer through inhibiting the upregulations of MDR1 and P-gp induced by morphine.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Alcaloides/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Genes MDR , Neoplasias Pulmonares/fisiopatologia , Morfina/farmacologia , Quinolizinas/efeitos adversos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Alcaloides/administração & dosagem , Animais , Neoplasias Pulmonares/genética , Camundongos , Quinolizinas/administração & dosagem
18.
PLoS One ; 15(4): e0230188, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240205

RESUMO

BACKGROUND: Patients with metastatic lung cancer can have severe cancer-related symptoms and treatment-induced side effects. Exercise is beneficial for patients with metastatic lung cancer; however, little information is available on guiding patients how to perform exercise during hospitalization. The purpose of this qualitative study was to understand exercise experiences in patients with metastatic lung cancer. METHODS: Patients with metastatic lung cancer (n = 24) participated in face-to-face in-depth interviews at an inpatient ward of a medical center in central Taiwan. Interview transcripts were evaluated using narrative analysis to extract and validate themes. RESULTS: Three primary themes were identified: (1) modifying exercise to maximize physical functions; (2) living with symptoms and frustration, but still exercising; and (3) doing exercise to sustain hopes, inner power, and life. Secondary findings included: (1) adopting walking as their main form of exercise because of its convenience; and (2) among patients with severe symptoms, adjusting exercise towards shorter time durations and shorter distances, slower speeds, and higher frequencies. CONCLUSIONS: The study found physically active lung cancer patients, although with metastatic condition, adjusted their exercise activities to balance disease and treatment-induced deteriorations and boost themselves to feel hope and fight for cancer. However, the results may not be applicable to physically inactive patients. Future research to explore experiences from those with even worse physical conditions and further helping them to take some mild exercise to enhance the positive side of cancer experiences are suggested.


Assuntos
Terapia por Exercício/psicologia , Exercício Físico/psicologia , Neoplasias Pulmonares/psicologia , Motivação/fisiologia , Idoso , Antineoplásicos/uso terapêutico , Terapia por Exercício/métodos , Feminino , Hospitalização , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/fisiopatologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Comportamento Sedentário , Inquéritos e Questionários , Taiwan , Caminhada/fisiologia , Caminhada/psicologia
19.
Aust J Gen Pract ; 49(4): 175-181, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32233342

RESUMO

BACKGROUND: International guidelines recommend exercise for all people with cancer. Effective supportive care interventions are required for people diagnosed with lung cancer to reduce morbidity associated with the disease process, frequently occurring comorbidities and treatment-related side effects. OBJECTIVE: This article summarises the evidence regarding the safety, effectiveness and patient experiences of exercise and physical activity interventions for people with lung cancer. DISCUSSION: Exercise interventions for people with lung cancer are safe and effective at improving physical fitness, muscle strength and patient-reported outcomes including cancer-related fatigue, dyspnoea and health-related quality of life. Increasing evidence supports the use of exercise prior to treatment (prehabilitation) to improve outcomes following surgery. Individuals with lung cancer should be encouraged to be as physically active as possible. Throughout the patient's cancer journey, consideration and prescription of individualised exercise is an important component of care. General practitioners are well placed to coordinate this care, often in conjunction with exercise physiologists or physiotherapists.


Assuntos
Exercício Físico/fisiologia , Exercício Físico/psicologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/psicologia , Humanos , Força Muscular/fisiologia , Cuidados Paliativos/métodos , Qualidade de Vida/psicologia
20.
Medicine (Baltimore) ; 99(9): e19346, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118771

RESUMO

RATIONALE: Available literature states that the histological subtype of the gastrointestinal stromal tumor (GIST) with pulmonary metastasis is often spindle cell type. To our knowledge, this is the first report of the GIST with pulmonary metastasis of very uncommon epithelioid subtype. PATIENT CONCERNS: We report a 63-year-old male presenting with the symptom of bloodstained sputum without obvious inducement. The patient had no chest pain, low back pain, fatigue, fever or night sweats symptoms. DIAGNOSES: Combined chest digital radiography and the history of the patient who presented with the colon GIST of the epithelioid subtype two years ago that the mass may be a metastasis tumor. Combined with morphological and immunohistochemical staining results, a pathological diagnosis of the GIST with pulmonary metastasis was considered. INTERVENTIONS: Right lobectomy and partial upper lobectomy were performed. OUTCOMES: The patient had not experienced any noticeable symptom and recurrent tumors at 6 months follow-up. LESSONS: We report a rare case of the GIST with pulmonary metastasis of epithelioid subtype. This case is of great significance to the pathologist's clinical work. For pathologists, if an epithelioid tumor in the lung is found, it is necessary to check whether the gastrointestinal tract also has the tumor, which may be an epithelioid GIST with pulmonary metastasis.


Assuntos
Tumores do Estroma Gastrointestinal/complicações , Neoplasias Pulmonares/etiologia , Biomarcadores Tumorais/análise , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/fisiopatologia , Humanos , Pulmão/anormalidades , Pulmão/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Metástase Neoplásica/fisiopatologia
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