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BACKGROUND: The ATS/JRS/ALAT Guidelines for the Diagnosis of Hypersensitivity Pneumonitis (GL for HP) were published in 2020. Humidifier lung and summer-type HP are forms of HP, but it is unclear whether they can be diagnosed using GL for HP. This study examined the level of confidence where humidifier lung and summer-type HP can be diagnosed with GL for HP. METHODS: Data from 23 patients with humidifier lung and 20 patients with summer-type HP (mean age, 67.3 and 57.4 years, respectively) diagnosed between October 2012 and January 2022 were retrospectively reviewed. We evaluated high resolution computed tomography (HRCT) patterns, bronchoalveolar lavage fluid (BALF) findings, exposures, and histopathological findings to determine the level of confidence where a diagnosis of HP could be made using the GL for HP. RESULTS: HRCT pattern was classified as typical HP in 5 (22%) and compatible with HP in 18 (78%) patients with humidifier lung and considered as typical HP in 17 (85%) and compatible with HP in 3 (15%) patients with summer-type. The confidence level for diagnosis of HP was definite in 2 (8.7%), moderate in 14 (60.9%), and low in 7 (30.4%) patients with humidifier lung. It was definite in 12 (60%), high in 3 (15%), and moderate in 5 (25%) patients with summer-type HP. CONCLUSIONS: GL for HP showed utility in diagnosing humidifier lung in many patients with a moderate to low confidence. However, there was a definite to high confidence for patients with summer-type HP.
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Alveolite Alérgica Extrínseca , Tricosporonose , Humanos , Tricosporonose/patologia , Umidificadores , Estudos Retrospectivos , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Alveolite Alérgica Extrínseca/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologiaRESUMO
Background: The indication for and the timing of surgery in patients with pleural infection remains unclear. Determining the need for surgery in patients with pleural infection may help in the early consultation of surgeons. Methods: Data of 167 consecutive patients with pleural infection were retrospectively reviewed. To detect a surgical indicator, the variables of patients who required surgery were compared with those of patients who were cured by non-surgical therapy (n=94) and patients resistant to the non-surgical therapy (n=73; 62 underwent surgery, and 11 showed recurrence or disease-related death after non-surgical treatment). Prognosis and timing of surgery were analyzed by comparing three groups: patients who underwent surgery within 7 days of admission (n=33), patients who underwent surgery after 7 days of admission (n=29), and patients who underwent non-surgical therapy (n=105). Results: The presence of multifocal locules, including a locule on the anterior mediastinum side (LAMS) was a significant indicator of resistance to initial non-surgical therapy, as compared to the absence of locules (P<0.0001), a single locule (P<0.0001), or multifocal locules without a LAMS (P=0.0041). Recurrence and mortality were not observed in the patients who underwent surgery within 7 days of admission, and the hospitalization period (P=0.0071) and duration of C-reactive protein (CRP) improvement (P<0.0001) were significantly shorter in these patients compared with those who that underwent surgery after 7 days. Conclusions: In patients with pleural infection, the presence of multifocal locules, including a LAMS, was associated with resistance to non-surgical therapy. Early surgery should be considered for these patients to shorten the hospitalization period and improve the prognosis.
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Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is often fatal. A straightforward staging system for AE-IPF would improve prognostication, guide patient management, and facilitate research. The aim of study is to develop a multidimensional prognostic AE-IPF staging system that uses commonly measured clinical variables. This retrospective study analyzed data from 353 consecutive patients with IPF admitted to our hospital during the period from January 2008 through January 2018. Multivariate analysis of information from a database of 103 recorded AE-IPF cases was used to identify factors associated with 3-month mortality. A clinical prediction model for AE-IPF was developed by using these retrospective data. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of this model. Logistic regression analysis showed that PaO2/FiO2 ratio, diffuse HRCT pattern, and serum C-reactive protein (CRP) were significantly associated with 3-month mortality; thus, PaO2/FiO2 ratio < 250 (P), CRP ≥ 5.5 (C), and diffuse HRCT pattern (radiological) (R) were included in the final model. A model using continuous predictors and a simple point-scoring system (PCR index) was developed. For the PCR index, the area under the ROC curve was 0.7686 (P < 0.0001). The sensitivity of the scoring system was 78.6% and specificity was 67.8%. The PCR index identified four severity grades (0, 1, 2, and 3), which were associated with a 3-month mortality of 7.7%, 29.4%, 54.8%, and 80%, respectively. The present PCR models using commonly measured clinical and radiologic variables predicted 3-month mortality in patients with AE-IPF.
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Fibrose Pulmonar Idiopática/mortalidade , Insuficiência Respiratória/mortalidade , Exacerbação dos Sintomas , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/diagnóstico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Curva ROC , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricosRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting ß2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. METHODS: Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. RESULTS: Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). CONCLUSIONS: We believe this treatment combination is optimal for patients with lung cancer and COPD.
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Adenocarcinoma/complicações , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Neoplasias Pulmonares/complicações , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adenocarcinoma/cirurgia , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Gerenciamento Clínico , Quimioterapia Combinada , Feminino , Volume Expiratório Forçado , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Pneumonectomia , Prognóstico , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: The response rate for osimertinib is high among patients with untreated epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). However, there exist no biomarkers to predict the efficacy of the same. This study investigated whether BIM-γ mRNA expression in circulating tumor cells (CTCs) predicts poor outcomes for osimertinib treatment in patients with EGFR mutation-positive NSCLC. METHODS: Patients with advanced EGFR-tyrosine kinase inhibitor-untreated NSCLC or post-operative recurrence with EGFR-sensitive mutations (exon 19 deletion or L858R mutation) were included. Informed consent was obtained from all participants. The candidate biomarker BIM-γ was measured in CTCs after blood collection (10 mL of whole blood) at baseline. CTCs were collected with the ClearCell FX system, and quantitative real-time PCR was performed. Relative expression of BIM-γ mRNA from CTCs, as normalized to the reference gene (GAPDH mRNA), was calculated using the KCL22 cell line for calibration. RESULTS: We enrolled 30 EGFR mutation-positive NSCLC patients treated with osimertinib during the period from April 2018 through December 2019. All the patients had an EGFR mutation at the primary site: exon 19 deletion in 15 cases and L858R in 15 cases. Median CTC count at baseline was 12 (range 3-127)/7.5 mL, and median BIM-γ mRNA expression was 0.073 (range 0-1.37). Furthermore, the response rate to osimertinib was worse in patients with high than in those with low BIM-γ mRNA expression (n = 15 each) (26.6% vs. 73.3%, respectively; p = 0.011). Progression-free survival did not significantly differ between groups (p = 0.13). CONCLUSIONS: BIM-γ mRNA overexpression in CTCs from EGFR mutation-positive NSCLC patients is a potential a biomarker for poor response to osimertinib. CLINICAL TRIAL REGISTRATION NUMBER: UMIN:00032055.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases , RNA Mensageiro/genéticaRESUMO
OBJECTIVES: Silicone airway stents are used to manage central airway stenosis or obstruction, although their impact on long-term survival remains unknown in patients with central airway stenosis or obstruction due to thoracic malignancy. In this study, we retrospectively analyzed the impact of silicone stents on survival. METHODS: We retrospectively analyzed clinical data of 106 patients with central airway stenosis or obstruction due to thoracic malignancy treated by stenting at Toho University Omori Medical Center between 1998 and 2018. RESULTS: Patients treated with silicone stents had significantly higher survival rates than patients treated with metallic stents (p = 0.0173). Silicone stents patients also had significantly more additional treatments for thoracic malignancy after stenting than metallic stents patients (p = 0.0007). Notably, significantly more silicone stents patients underwent chemoradiotherapy or radiotherapy (p = 0.0268, p = 0.0300). During multivariate analyses, the additional treatment, including chemoradiotherapy or radiotherapy, was an independent optimal prognostic factor. CONCLUSIONS: Silicone stents patients had significantly higher survival rates than metallic stents patients. Although stenting for airway stenosis or obstruction due to thoracic malignancy may be mainly palliative, additional treatments after stenting should be considered to improve the prognoses of patients with airway stenosis or obstruction due to thoracic malignancy.
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Obstrução das Vias Respiratórias , Neoplasias Torácicas , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/terapia , Broncoscopia , Constrição Patológica , Humanos , Estudos Retrospectivos , Silicones , Stents , Neoplasias Torácicas/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Ultrasonic humidifier lung is a rare form of hypersensitivity pneumonitis (HP), and its clinical and radiological features are unclear. This study examined the clinical and radiological characteristics of humidifier lung. METHODS: Data from 18 patients with humidifier lung (mean age, 67.3 years) diagnosed during October 2012 through April 2018 were retrospectively reviewed. We compared clinical, laboratory, and CT findings and bronchoalveolar lavage fluid (BALF) characteristics of these patients with those of 19 patients with summer-type HP (mean age, 57.4 years). RESULTS: Cough and dyspnea were the most common symptoms. White blood cell count and serum C-reactive protein titers were higher for humidifier lung than for summer-type HP. Serum levels of Krebs von den Lungen-6 and surfactant protein D were significantly lower for humidifier lung than for summer-type HP. The most common chest CT findings in humidifier lung were ground-glass opacities (88.9%) and mosaic attenuation (50.0%). Centrilobular ground glass nodules were less common in humidifier lung than in summer-type HP (27.8% vs 63.1%; P = 0.043). Peribronchovascular or subpleural nonsegmental consolidation was more frequent in humidifier lung than in summer-type HP (44.4% vs 5.3%; P = 0.013). Lymphocyte fractions in BALF specimens were significantly lower for humidifier lung than for summer-type HP (37.3% vs 69.0%; P < 0.001). Neutrophil fractions were higher for humidifier lung, but the difference was not significant (22.1% vs 8.1%; P = 0.153). The CD4/8 ratio was higher for humidifier lung than for summer-type HP (1.7 vs 0.8; P = 0.003). CONCLUSIONS: The clinical and radiological characteristics of humidifier lung differ from those of summer-type HP.
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Alveolite Alérgica Extrínseca/diagnóstico , Tomografia Computadorizada por Raios X , Tricosporonose/diagnóstico , Idoso , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Biomarcadores/análise , Biomarcadores/sangue , Contagem de Células Sanguíneas , Líquido da Lavagem Broncoalveolar/citologia , Proteína C-Reativa , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tricosporonose/diagnóstico por imagemRESUMO
Long noncoding RNAs (lncRNAs) have been reported to be involved in the physiological and pathological processes of tumor pathogenesis, including epithelialmesenchymal transition (EMT). However, epidermal growth factor receptor (EGFR)tyrosine kinase inhibitor (TKI) resistance is a major challenge in the treatment of advanced and recurrent EGFRmutant lung adenocarcinoma. An increased understanding of the underlying mechanisms would aid in the development of effective therapeutic strategies against EGFRTKI resistance, strategies which are urgently required for clinical therapy. In this study, long noncoding RNA LINC00460 was identified as a novel marker of a poor response to EGFRTKI and prognosis. In lung cancer cells, LINC00460 promoted EGFRTKI resistance as a competitive decoy for miR1495p, thereby facilitating interleukin (IL)6 expression and inducing EMTlike phenotypes. The knockdown or knockout of LINC00460 in gefitinibresistant nonsmall cell lung cancer cells restored the response to EGFRTKI. In addition, as compared with patients with a low LINC00460 expression in tumors, those with a high LINC00460 expression had a significantly shorter progressionfree survival following gefitinib therapy, and a shorter overall survival. Therefore, LINC00460 may be a predictor of and potential therapeutic target for EGFRTKI resistance.
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Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Mutação , RNA Longo não Codificante/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Inibidores de Proteínas Quinases , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUND: Reactive oxygen species (ROS) can play a role in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) by contributing to epithelial damage. Bcl-2-like 11 (BIM) is involved in the generation of ROS via forkhead box O3 (FOXO3), and a BIM deletion polymorphism related to apoptosis has been reported to be specific to Asians. Here we examine the clinical features of IPF in patients with BIM deletion polymorphism. METHODS: In this single-center retrospective study, we reviewed the medical records of 63 patients with IPF who were treated at our hospital from January 2006 through April 2018. Patients with and without BIM deletion polymorphism were compared in relation to clinical characteristics, pulmonary function test results, frequency of acute exacerbation (AE)-IPF, and redox status [including oxidized glutathione (GSSG), reduced glutathione (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoprostane (8-iso)] at baseline and at 1 and 2 years after treatment. RESULTS: No fatal AE-IPF occurred in patients with BIM deletion polymorphism (0% vs. 36.4% of polymorphism-negative cases; P=0.038). Change in forced vital capacity from baseline (ΔFVC) at 2 years was significantly lower in patients with the BIM deletion polymorphism than in those without the polymorphism (â0.42±0.50 vs. â0.88±0.83 L, respectively; P=0.045). Total blood glutathione (tGSH) was significantly higher in patients with the deletion polymorphism than in those without the polymorphism (988±48.3 vs. 858±25.8 µM, respectively; P=0.042). 8-iso was significantly lower in the former group (246.1±81.6 vs. 400.9±334.1 pg/mL, respectively; P=0.022). CONCLUSIONS: IPF patients with BIM deletion polymorphism had a good redox balance and may thus have a better clinical outcome than patients without this polymorphism.
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BACKGROUND: Recent clinical trials demonstrated the benefits of several guided-bronchoscopy technologies for the diagnosis of peripheral pulmonary lesions (PPLs). However, introduction of these technologies is expensive. Therefore, in clinical practice, these are unavailable in many hospitals. In contrast, virtual bronchoscopy (VB) using the computed tomography (CT) workstation can be made available immediately without additional cost as many hospitals already have the CT scan facility. However, the effectiveness of VB alone remains to be shown. OBJECTIVES: The aim of this study was to investigate the effect of VB using the CT workstation in hospitals performing conventional bronchoscopy. METHODS: Results from consecutive patients who underwent bronchoscopy for small PPLs (major diameter ≤30 mm) were retrospectively reviewed. Sixty-nine patients who underwent bronchoscopy without VB from April 2014 to March 2015 and 56 patients who underwent bronchoscopy with VB from April 2015 to December 2015 were assigned to non-VB and VB groups, respectively. We compared the two groups and analyzed the factors affecting the diagnostic yield. RESULTS: The VB group had a significantly higher diagnostic yield than the non-VB group (57.1 vs. 33.3%; p = 0.008). In the multivariate analysis, VB was identified as a significant factor affecting the diagnostic yield (odds ratio: 3.30, p = 0.011). CONCLUSIONS: In the conventional bronchoscopy settings, VB using the CT workstation is efficient for the diagnosis of PPLs when other guided-bronchoscopy techniques are unavailable.
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Broncoscopia/estatística & dados numéricos , Imageamento Tridimensional , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/instrumentação , Realidade Virtual , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia/métodos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Fatal acute exacerbation (AE) of interstitial pneumonia (IP) sometimes occurs after chemotherapy for lung cancer. We developed and evaluated a scoring system for assessing AE risk after chemotherapy in patients with lung cancer associated with IP. METHODS: A review of medical records identified 109 patients with primary lung cancer associated with IP who had received chemotherapy at our center during the period from June 2007 through September 2017. We developed a model to score AE risk after chemotherapy in this patient group, and logistic regression was used to evaluate the model. RESULTS: The anticancer agent score was determined by using AE rates reported in past studies. The risk score was calculated with the following formula: (1 × anticancer agent score) + (3 × smoking history [>70 pack-years]) + (4 × history of steroid use) + (3 × %diffusing capacity of lung carbon monoxide [<50%]). Patients were then classified into three groups. The AE incidence rate was 12% for a risk score of 0-5, 47% for a score of 6-10, and 66.7% for a score of ≥11. The sensitivity of the scoring system was 78.6% and specificity was 67.8%. CONCLUSIONS: The present scoring system was able to identify IP patients at high risk for AE after chemotherapy for lung cancer associated with IP.
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Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Thymic carcinoma is a relatively rare and aggressive thymic epithelial tumor. Herein, we report successful treatment of thymic carcinoma with pembrolizumab. A 68-year-old woman was admitted to our hospital for evaluation of chest pain. Chest computed tomography showed a mass in the anterior mediastinum and lymphadenopathy in the left cervical lymph node. Analysis of biopsy specimens detected squamous cell carcinoma in the left cervical lymph node, and immunohistochemical analysis showed 100% expression of programmed death-ligand 1 (PD-L1). Masaoka-Koga stage IVb thymic carcinoma was ultimately diagnosed. Since 3 cycles of first-line chemotherapy did not result in improvement, pembrolizumab was administered as second-line treatment every 3 weeks at a dosage of 200 mg. After 3 cycles of pembrolizumab treatment, the size of the anterior mediastinal tumor and metastatic lesions had notably decreased. Pembrolizumab may prove to be an effective therapy for thymic carcinoma with high PD-L1 expression.
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Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy.
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Adenocarcinoma/tratamento farmacológico , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/administração & dosagem , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Apoptose/efeitos dos fármacos , Proteína 11 Semelhante a Bcl-2/genética , Intervalo Livre de Doença , Feminino , Gefitinibe , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
As a treatment for superficial transitional cell carcinoma, Bacillus Calmette-Guerin (BCG) intravesical instillation can rarely cause unpredictable systemic side effects. We describe a patient admitted due to continuous pyrexia and general fatigue. He was previously treated with intravesical BCG. Laboratory data indicated a hepatic disorder, and chest computed tomography revealed extensive bilateral miliary nodules. Transbronchial lung biopsy specimens showed several small noncaseating granulomas. The diagnosis was unsolved on the basis of acid fast staining, polymerase chain reaction and microbiological cultures, so we considered the possibility of BCG side effect-induced granuloma. Two months after treatment with antituberculous agents and corticosteroids, his clinical symptoms were improved.
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Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/efeitos adversos , Tuberculose Miliar/etiologia , Administração Intravesical , Antituberculosos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Tuberculose Miliar/tratamento farmacológicoRESUMO
The aim of this prospective study was to evaluate the efficacy and feasibility of bevacizumab combined with vinorelbine therapy in patients with previously treated non-squamous non-small-cell lung cancer (nonSq-NSCLC). Patients who had received at least one prior chemotherapy course were eligible for this study. The patients were treated with vinorelbine (25 mg/kg on days 1 and 8) and bevacizumab (15 mg/kg on day 1), which was repeated every 3 weeks until the development of progressive disease or unacceptable toxicity. Between June, 2011 and January, 2013, 15 patients were enrolled. The response and disease control rates were 26.7 and 73.3%, respectively. The median progression-free survival was 2.1 months and the median overall survival was 34.1 months. Grade 3-4 phlebitis occurred in 3 patients. Therefore, the combination of vinorelbine and bevacizumab was found to be effective in patients with previously treated nonSq-NSCLC, but physicians must be aware of the risk of phlebitis associated with this regimen.
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Background: Idiopathic interstitial pneumonia (IIP) is associated with increased risk of acute exacerbation after lung surgery, which has a poor prognosis and can be fatal. Although some studies have investigated acute exacerbation of IIP after lung surgery, the incidence and risks of acute exacerbation of IIP after nonpulmonary surgery have not been reported. The aim of present study to evaluate the characteristics and risk factors for acute exacerbation of IIP after nonpulmonary surgery. Methods: We retrospectively reviewed the clinical characteristics of 2908 consecutive patients (1620 men, 1288 women; mean age, 61.7) who underwent nonpulmonary surgery under general anesthesia between April 2008 to April 2013. Using preoperative chest computed tomography images, we identified IIP cases and compared preoperative characteristics, laboratory findings, and anesthesia conditions among patients who did and did not develop AE. Results: We extracted 103 IIP patients who underwent nonpulmonary surgery; postoperative acute exacerbation of IIP developed in 8 (7.8%). Univariate analysis identified several risk factors, namely, emergency surgery, preoperative prednisolone use, high serum C-reactive protein, lactate dehydrogenase, white blood cell count, low serum albumin and propofol use during anesthesia. Conclusion: The results suggest that the incidences of postoperative acute exacerbation of IIP are similar after nonpulmonary and pulmonary surgery. In addition, propofol use during anesthesia is a possible risk factor for acute exacerbation of IIP after nonpulmonary surgery. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 156-164).
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AIM: This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR). RESULTS: BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism inside tumors (p=0.038) and around tumors (p=0.0024). Relative BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism (p=0.0017). Patients with BIM-γ had significantly shorter progression-free survival than those without BIM-γ (median: 304 vs. 732 days; p=0.023). CONCLUSION: Expression of BIM-γ mRNA and BIM deletion polymorphism were strongly associated. BIM-γ overexpression may have a role in apoptosis related to EGFR-tyrosine kinase inhibitor.
Assuntos
Proteína 11 Semelhante a Bcl-2/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Estudos de Associação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/efeitos dos fármacos , Proteína 11 Semelhante a Bcl-2/biossíntese , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Gefitinibe , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo Genético , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Deleção de SequênciaRESUMO
A 30-year-old man was admitted to Toho University Omori Medical Center for assessment of right chest pain and fever. Chest computed tomography (CT) revealed an anterior mediastinal tumor sized 11.0×6.0×5.0 cm, with right pleural effusion. The laboratory analysis revealed elevated white blood cell count (11,000/µl), C-reactive protein (4.1 mg/dl) and cytokeratin fragment (CYFRA; 12.7 ng/ml; normal, <2 ng/ml). The level of CYFRA in the pleural effusion was also markedly elevated (143 ng/ml). On the first day after admission (6 days after the initial CT), there was a mild regression on CT (10.0×5.5×4.4 cm; reduction rate, 26.7%), with decrease of the pleural effusion volume. A CT-guided needle biopsy was performed, but the findings were not conclusive, as most of the tissue was necrotic. Seven days later (13 days after the initial CT), a CT revealed further regression (9.5×5.4×4.2 cm; reduction rate, 34.7%) with disappearance of the pleural effusion. The patient was followed up on an outpatient basis. At 35 days after the initial CT, the tumor continued to shrink without treatment (8.0×3.6×3.0 cm; reduction rate, 73.8%) and the serum CYFRA level had decreased to 0.8 ng/ml, although it had not returned to normal levels. At 62 days after the initial CT, the patient underwent surgical resection. The resected specimen was diagnosed as thymoma (World Health Organization type B2; Masaoka classification, stage II), with prominent degeneration and necrosis. One possible cause of the spontaneous regression may be increased internal pressure, probably associated with rapid tumor growth, leading to massive necrosis with resulting chest pain, inflammatory reaction with pleural effusion and subsequent tumor regression. The serum CYFRA level may be a useful marker for the evaluation of the clinical course of thymoma with extensive necrosis.
RESUMO
Antiphospholipid syndrome (APS) is clinically characterized by arterial or venous thrombosis; however, non-thromboembolic lung manifestations, such as diffuse alveolar hemorrhage (DAH), have also been previously reported. DAH is relatively common in APS patients with systemic lupus erythematosus, although it is rare in primary APS. We encountered a 78-year-old man who presented with hemoptysis and dyspnea. Chest CT showed diffuse ground-glass opacity with pulmonary thromboembolism. He was successfully treated with corticosteroids and heparin; however, DAH recurred after the corticosteroid treatment was stopped. The treatment was intricate due to the concurrent bleeding and thrombotic manifestations.
Assuntos
Corticosteroides/uso terapêutico , Síndrome Antifosfolipídica/diagnóstico , Dispneia/etiologia , Glucocorticoides/uso terapêutico , Hemoptise/etiologia , Hemorragia/complicações , Lúpus Eritematoso Sistêmico/complicações , Embolia Pulmonar/complicações , Idoso , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/terapia , Diagnóstico Diferencial , Humanos , Lúpus Eritematoso Sistêmico/terapia , Masculino , Embolia Pulmonar/terapia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND OBJECTIVE: Treatment with pirfenidone may slow the decline in vital capacity and increase progression-free survival (PFS) in idiopathic pulmonary fibrosis (IPF). The effects of combination therapy with inhaled N-acetylcysteine (NAC) and pirfenidone are unclear. We assessed the effects of this combination therapy in patients with advanced IPF. METHODS: Patients with a diagnosis of advanced IPF (Japanese Respiratory Society stage III/IV IPF) and a relative decline in forced vital capacity (FVC) of ≥ 10% within the previous 6 (± 2) months were enrolled. Outcomes were evaluated in a 12-month follow-up pulmonary function test. Treatment was considered ineffective if the decline in FVC was ≥ 10% and effective if the decline was <10%. We compared clinical characteristics, effectiveness and PFS between patients receiving inhaled NAC plus pirfenidone (n = 24) and those receiving pirfenidone alone (control; n = 10). RESULTS: Data from 34 IPF patients (age range, 59-82 years) were analysed. At the 12-month follow-up examination, treatment was deemed effective in 8 of 17 (47%) patients receiving NAC plus pirfenidone and in 2 of 10 (20%) receiving pirfenidone alone. The annual rate of change in FVC was -610 mL in the NAC plus pirfenidone group and -1320 mL in the pirfenidone group (P < 0.01). PFS was longer (304 days) in the NAC plus pirfenidone group than in the pirfenidone group (168 days; P = 0.016). CONCLUSIONS: Combination treatment with inhaled NAC and oral pirfenidone reduced the rate of annual FVC decline and improved PFS in patients with advanced IPF.