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1.
Sci Rep ; 13(1): 18126, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872370

RESUMO

In this study, we aimed to investigate the feasibility of serum Krebs von den Lungen-6 (KL-6) as a potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom KL-6 was measured to differentiate between pneumonia and ILD (category 1), diagnose and assess the severity of suspicious ILD (category 2), or evaluate baseline levels before cancer treatment (category 3). Among 1,297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 195 patients. In categories 1-2, median KL-6 level was higher in drug-induced ILD or acute exacerbation of underlying ILD than in no ILD or radiation-induced pneumonitis, and it was correlated with the severity of TR-ILD. High KL-6 level (cut-off: > 436U/mL) was an independent risk factor for severe TR-ILD, and low KL-6 level with high procalcitonin level (> 0.5 ng/mL) could exclude severe TR-ILD. Patients with severe TR-ILD had worse overall survival than those without, whereas high baseline KL-6 level was associated with worse survival, especially in patients without severe TR-ILD. Therefore, serum KL-6 may be a surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspected ILD and before lung cancer treatment.


Assuntos
Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/complicações , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/complicações , Pulmão , Biomarcadores , Fatores de Risco , Mucina-1
2.
PLoS One ; 17(12): e0278610, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36454973

RESUMO

OBJECTIVE: Pulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study aimed to evaluate the risk factors for cerebral complications in patients with PAVMs. METHODS: We retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital. RESULTS: Fifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16-250.31; P = 0.038). CONCLUSION: Older age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs.


Assuntos
Malformações Arteriovenosas , Embolização Terapêutica , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Fatores de Risco , Doenças Raras , Centros de Atenção Terciária
3.
Respir Med Case Rep ; 40: 101759, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340867

RESUMO

Tracheal tumors are rare diseases. They can cause narrowing of a central airway, a severe respiratory distress, and death. The objective of this case series is to highlight the role of rigid bronchoscopy in diagnosing and treating carina masses which are difficult to remove surgically. Tumor excision was performed by the rigid bronchoscopic intervention. Additional treatment was administered according to the diagnosis of each individual patient. After the procedure, patients' symptoms were improved and stenotic central airways were reopened. Rigid bronchoscopy can be a good therapeutic option to reestablish airway patency and a bridge treatment for further definitive treatment.

4.
Thorax ; 77(9): 865-872, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35086913

RESUMO

OBJECTIVE: Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that are engaged in a number of diseases, but their roles in acute respiratory distress syndrome (ARDS) are not fully examined yet. This study aimed to examine levels and functions of MAIT cells in patients with ARDS. METHODS: Peripheral blood samples from patients with ARDS (n=50) and healthy controls (HCs, n=50) were collected. Levels of MAIT cells, cytokines, CD69, programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) were measured by flow cytometry. RESULTS: Circulating MAIT cell levels were significantly reduced in patients with ARDS than in HCs. MAIT cell levels were inversely correlated with disease severity and mortality. Cytokine production profiles in MAIT cells showed that percentages of interleukin (IL)-17 producing MAIT cell were significantly higher in patients with ARDS than in HCs. Patients with ARDS exhibited higher expression levels of CD69, PD-1 and LAG-3 in circulating MAIT cells. Moreover, levels of MAIT cells and expression levels of CD69, PD-1 and IL-17 in MAIT cells were higher in bronchoalveolar lavage fluid samples than in peripheral blood samples. Our in vitro experiments showed that MAIT cells triggered macrophages to produce proinflammatory cytokines such as tumour necrosis factor-α, IL-1ß and IL-8. CONCLUSIONS: This study demonstrates that circulating MAIT cells are numerically deficient in patients with ARDS. In addition, MAIT cells were found to be activated, migrate into lung, secrete IL-17 and then stimulate macrophages. These findings suggest that MAIT cells contribute to the worsening of inflammation in the lung of patients with ARDS.


Assuntos
Células T Invariantes Associadas à Mucosa , Síndrome do Desconforto Respiratório , Citocinas/metabolismo , Humanos , Interleucina-17/metabolismo , Ativação Linfocitária , Células T Invariantes Associadas à Mucosa/metabolismo , Receptor de Morte Celular Programada 1/metabolismo
5.
Thorac Cancer ; 12(10): 1598-1604, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33811467

RESUMO

BACKGROUND: We report a subgroup analysis of afatinib with respect to its efficacy, safety, and the long-term survival of patients in a Named Patient Use program at a single institution. METHODS: We analyzed 60 patients with stage IV non-small cell lung cancer (NSCLC) who had been treated with ≥1 line of platinum-based chemotherapy and had activating epidermal growth factor receptor (EGFR) mutations or disease control for ≥6 months with prior EGFR inhibitors. Afatinib was started on a daily dose of 50 mg, which was decreased according to the adverse events and tolerability. RESULTS: A total of 13 patients achieved partial remission, whereas 33, 12, and two showed stable disease, had progression, and were not evaluable, respectively, resulting in an objective response rate and disease control rate of 21.7% and 76.7%, respectively. The median progression-free survival (PFS) was 5.4 (95% confidence interval [CI]: 4.0-7.7) months and median overall survival (OS) was 10.1 (8.5-13.6) months. Toxicities leading to drug discontinuation were experienced by four patients (6.7%). Grade 3 diarrhea occurred in 10 patients (16.7%), and afatinib dose reductions were required in 35 patients. The PFS and OS were significantly longer for patients whose dose was reduced to 40 or 30 mg than for those without dose reduction (7.0 vs 3.1 months and 13.5 vs 8.1 months, respectively, p < 0.05). CONCLUSIONS: The efficacy of afatinib was similar to that identified in the global data without unexpected adverse events. Survival analyses support the currently approved dose of afatinib as first-line treatment for NSCLC.


Assuntos
Afatinib/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/uso terapêutico , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Afatinib/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cloridrato de Erlotinib/farmacologia , Feminino , Gefitinibe/farmacologia , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia
6.
Medicine (Baltimore) ; 100(4): e24040, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530198

RESUMO

RATIONAL: Hemocoagulase, a hemostatic, is used in patients with trauma, gastrointestinal bleeding, or pulmonary hemorrhage or those undergoing surgery. However, paradoxical bleeding after hemocoagulase administration is not considered a clinically significant adverse effect. Here, we report a case of paradoxical pulmonary hemorrhage associated with hypofibrinogenemia after administration of the hemocoagulase batroxobin in a patient with hemoptysis. PATIENT CONCERNS: An 86-year-old woman complained of hemoptysis during hospitalization with organophosphate poisoning. Hemocoagulase was administered to manage bleeding; however, bleeding signs, such as hemoptysis, massive epistaxis, and ecchymosis, recurred. DIAGNOSES: The patient was diagnosed with acquired hypofibrinogenemia on the basis of the reduced plasma fibrinogen level after hemocoagulase administration and lack of other causes of bleeding. INTERVENTION: Hemocoagulase administration was discontinued, and fibrinogen-containing plasma products were administered. OUTCOMES: The plasma fibrinogen level normalized and bleeding signs did not recur. LESSONS: It is necessary to measure plasma fibrinogen levels regularly in patients undergoing hemocoagulase administration and discontinue its administration when acquired hypofibrinogenemia is detected.


Assuntos
Afibrinogenemia/tratamento farmacológico , Batroxobina/efeitos adversos , Hemorragia/etiologia , Pneumopatias/etiologia , Afibrinogenemia/complicações , Idoso de 80 Anos ou mais , Batroxobina/uso terapêutico , Feminino , Fibrinogênio/administração & dosagem , Hemoptise/etiologia , Hemostáticos , Humanos
7.
PLoS One ; 16(2): e0246296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33539407

RESUMO

OBJECTIVE: Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP. METHODS: We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC). RESULTS: The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016). CONCLUSIONS: Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.


Assuntos
Pneumonia por Pneumocystis/mortalidade , Pneumonia por Pneumocystis/fisiopatologia , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Hospedeiro Imunocomprometido/fisiologia , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/patogenicidade , Pneumonia por Pneumocystis/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 100(6): e24745, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578625

RESUMO

ABSTRACT: Smoking is the leading cause of preventable death and a risk factor for cancer, but smoking cessation is difficult even in patients who need hospitalization. This study aimed to investigate the usefulness of an inpatient smoking cessation consultation program and to analyze the clinical factors associated with abstinence. In this observational study, patients received regular counseling for 6 months, and abstinence was objectively assessed via urine and exhaled carbon monoxide testing. Cessation rates were assessed at 4 weeks and 6 months, and clinical characteristics associated with cessation success were investigated. Of the 571 patients referred to participate in the program, 170 (29.8%) were enrolled, and only 2 (1.2%) used smoking cessation drugs in addition to counseling. The smoking cessation rate was 77.6% after 4 weeks and 59.1% after 6 months. The cessation rates were significantly higher in patients with cancer than in those without cancer at both timepoints (63.8% vs 21.9%, P < .001, 53.6% vs 12.5%, P < .001), and they were also higher in the first admission group than in the re-admission group (87.4% vs 74.7%, P = .033, 88.5% vs 76.1%, P = .037). In patients with lung cancer, progression-free survival and overall survival tended to be better in those enrolled in the program (P = .158, P = .183). In conclusion, the inpatient smoking cessation program was associated with a high abstinence rate. Most patients maintained cessation without medication, suggesting that initial admission, along with a cancer diagnosis, can provide enough motivation to abstain from smoking. In addition, the smoking cessation effort showed potential to improve survival during lung cancer treatment.


Assuntos
Neoplasias Pulmonares/mortalidade , Abandono do Hábito de Fumar/estatística & dados numéricos , Idoso , Institutos de Câncer , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia
9.
J Clin Med ; 9(12)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255360

RESUMO

We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete resection cases in 2013. GPx3 levels were measured by enzyme-linked immunosorbent assay. Statistical tests including t-tests and Cox proportional hazard regression analyses were performed. Totally, 135 patients were enrolled, and 39 (28.9%) showed relapse during the median follow-up period (63.60 months; range, 0.167-81.867). The mean GPx3 change was significantly higher in the recurrence group at 6 months (0.32 ± 0.38 vs. 0.15 ± 0.29, p = 0.016) and 12 months (0.40 ± 0.37 vs. 0.13 ± 0.28, p = 0.001). The high GPx3 change group showed significantly higher 60-months recurrence rates than the low group (48.1% vs. 25.2% at 3 months, p = 0.005; 54.5% vs. 28.9% at 6 months, p = 0.018; 38.3% vs. 18.3% at 12 months, p = 0.035). High GPx3 change at 3 months were independent risk factors of recurrence (hazard ratio (HR) 3.318, 95% confidence interval (CI), 1.582-6.960, p = 0.002) and survival (HR 3.150, 95% CI, 1.301-7.628, p = 0.011). Therefore, serum GPx3 changes after surgery may be useful predictive biomarkers for recurrence in lung cancer. Larger-scale validation studies are warranted to confirm these findings.

10.
Transl Lung Cancer Res ; 9(3): 507-514, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32676314

RESUMO

BACKGROUND: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient's medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients. METHODS: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated 'recommended' by WFO. Concordance between MDT and WFO was analyzed by Cohen's kappa value. RESULTS: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients. CONCLUSIONS: Treatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I-III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage.

11.
BMC Pulm Med ; 20(1): 71, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32199453

RESUMO

BACKGROUND: The concurrence of sarcoidosis and primary lung cancer is very rare. We report a very rare case with a delayed diagnosis of primary lung cancer due to its misdiagnosis as worsening of pulmonary sarcoidosis. CASE PRESENTATION: A 68-year-old man presented to the outpatient department for evaluation of a mass in the right hilar area with lymphadenopathies in subcarinal and both interlobar areas on chest computed tomography (CT). Sufficient core samples were obtained from subcarinal and bilateral interlobar lymph nodes using endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration (TBNA). EBUS could not reach the right hilar lymph node due to its high angle. The pathologic findings were consistent with sarcoidosis. After 5 months, chest CT revealed aggravation of the right upper paratracheal lymphadenopathy. Assuming worsening of sarcoidosis, he was prescribed an oral corticosteroid for 5 months. However, follow-up chest CT showed a newly developed right lower paratracheal lymphadenopathy and worsening right hilar lymphadenopathy. Bronchoscopy and EBUS were performed once again. Transbronchial lung biopsy from the right upper lobe and EBUS-TBNA from the right lower paratracheal lymph node revealed adenocarcinoma from the lung. CONCLUSIONS: Although coexistence of sarcoidosis and lung cancer is very rare, the clinician should consider the possibility of accompanying lung cancer in sarcoidosis patients who are not responding to initial corticosteroid therapy.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Idoso , Broncoscopia , Diagnóstico Tardio , Erros de Diagnóstico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Masculino , Tomografia Computadorizada por Raios X
12.
Thorac Cancer ; 11(2): 408-414, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31841269

RESUMO

BACKGROUND: We correlated the tumor proportion score (TPS) of programmed cell death ligand 1 (PD-L1, SP263 or 22C3) expression with the disease control rate (DCR, partial remission and stable disease), and progression free survival (PFS) after nivolumab or pembrolizumab treatment. METHODS: A total of 70 case records (55 males, 15 females) of patients with non-small cell lung cancer (NSCLC, 46 adenocarcinoma, 22 squamous cell carcinoma, and two others) were reviewed. The PD-L1 expressions were divided into High (SP263 ≥ 30%, 22C3 ≥ 80%) and Low groups (SP263 < 30%, 22C3 < 80%). In the combined analysis, the PD-L1 group was defined as High if either of the two stains was classified as High and defined as Low if both stains were classified as Low. RESULTS: Among the patients treated with nivolumab (n = 37), the SP263 High group showed higher DCR compared to the SP263 Low group (52.6% vs. 11.1%, P = 0.024). In patients treated with pembrolizumab (n = 33), no significant difference in DCR and PFS according to PD-L1 expression was observed. In the combined analysis (n = 36), patients in the PD-L1 High group showed significantly higher DCRs than those in the PD-L1 Low group (56.1% vs. 24.1%, P = 0.028). PFS was significantly longer in the PD-L1 High group than in the Low group (medians 4.1 vs. 1.6 months, respectively, P = 0.04). CONCLUSION: A high expression level of PD-L1 was correlated with a significantly higher DCR and longer PFS in NSCLC patients treated with nivolumab or pembrolizumab.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Thorac Cancer ; 10(10): 2045-2049, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31436031

RESUMO

Here, we report a case of myasthenia gravis and myopathy in a patient treated with nivolumab. A 76-year-old man who had been treated with four doses of nivolumab because of non-small cell lung cancer (NSCLC) presented with proximal-dominant muscle weakness and fluctuating ptosis and diplopia. Serologic studies revealed increased levels of muscle enzymes including creatine phosphokinase (2934 U/L), and acetylcholine receptor antibody was positive (1.31 nmol/L). Following electrodiagnostic study, he was diagnosed with myasthenia gravis and active stage of myopathy. After discontinuation of nivolumab, he was treated with corticosteroids, intravenous immunoglobulin G, and pyridostigmine. The neuromuscular symptoms and serologic abnormalities of the patient markedly improved. Currently, he is taking oral steroids and pyridostigmine without further immunotherapy.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Doenças Musculares/etiologia , Miastenia Gravis/etiologia , Nivolumabe/efeitos adversos , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoanticorpos/imunologia , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Doenças Musculares/diagnóstico , Miastenia Gravis/diagnóstico , Estadiamento de Neoplasias , Nivolumabe/uso terapêutico , Tomografia Computadorizada por Raios X
14.
J Cancer Res Clin Oncol ; 145(8): 2071-2082, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154543

RESUMO

PURPOSE: Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes. METHODS: ALK-FISH assays were performed in 1128 tumor specimens of NSCLC between January 2015 and June 2018. We retrospectively analyzed formalin-fixed paraffin-embedded (FFPE) tissues from previously confirmed FISH-positive (n = 199) and -negative (n = 920) cases. We recruited patients who had available tissue specimens and agreed to venous sampling. RNA was extracted from FFPE blocks, plasma, and platelets. Fusion RNA of echinoderm microtubule-associated protein-like 4 (EML4)-ALK was detected by quantitative PCR. RESULTS: Thirty-three FISH-positive and 28 FISH-negative patients were enrolled. In validation, data compared with FISH, RT-PCR using FFPE tissues showed 54.5% sensitivity, 78.6% specificity, and 75.5% accuracy. Liquid biopsy had higher sensitivity (78.8%), specificity (89.3%) and accuracy (83.6%). Higher positivity for liquid biopsy was shown in subgroups with delayed (≥ 6 months from diagnosis) blood sampling (plasma, 85.7%; platelets, 87.0%). In 26 patients treated with crizotinib, the platelet-positive subgroup showed longer median duration of treatment (7.2 versus 1.5 months), longer median progression-free survival (5.7 months versus 1.7 months), a higher overall response rate (70.6% versus 11.1%), and a higher disease control rate (88.2% versus 44.4%) than the platelet-negative subgroup. CONCLUSION: Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors.


Assuntos
Quinase do Linfoma Anaplásico/genética , Plaquetas/química , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/diagnóstico , Plasma/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue/métodos , Plaquetas/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA de Neoplasias/análise , Resistencia a Medicamentos Antineoplásicos/genética , Estudos de Viabilidade , Feminino , Humanos , Hibridização in Situ Fluorescente , Biópsia Líquida , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Células Neoplásicas Circulantes/patologia , Plasma/citologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Tuberc Respir Dis (Seoul) ; 82(3): 227-233, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30841018

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. METHODS: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. RESULTS: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS <1% group (64.83±9.38 years vs. 61.73±10.78 years, p=0.014), not in TPS ≥50% cutoff value (64.69 ± 9.39 vs. 62.36 ± 10.51, p= 0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ≥1% (40.8% vs. 25.8%, p=0.020) and TPS ≥50% groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ≥1% (r=0.826; 95% confidence interval, 0.736-0.916). CONCLUSION: PD-L1 expression, defined as TPS ≥1%, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

16.
Medicine (Baltimore) ; 98(9): e14699, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30817606

RESUMO

RATIONALE: Current guidelines for advanced non-small cell lung cancer (NSCLC) recommend the use of targeted agents for specific driver genes after confirming genetic alterations. Although epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement are usually mutually exclusive, EGFR and ALK co-alterations have been reported increasingly in cases of NSCLC. However, the optimal treatment for these cases has not been established. PATIENT CONCERNS: This case series describes three patients diagnosed with advanced non-squamous NSCLC who harbored EGFR and ALK co-alterations. The complaints for each case are as follows: 57-year-old woman with coughing and dyspnea in case 1, 32-year-old man with diplopia in case 2 and 77-year-old woman with chest discomfort in case 3. DIAGNOSES: Three never-smokers were diagnosed pathologically with stage IV adenocarcinoma of the lung. Subsequent molecular studies revealed the EGFR L858R mutation gene and ALK rearrangement, which were proven by real-time polymerase chain reaction and fluorescence in situ hybridization, respectively. INTERVENTIONS: All 3 patients received first-line therapy with EGFR-tyrosine kinase inhibitors (TKIs). Cases 1 and 2 were treated with ALK-TKIs as second-line therapy and received additional EGFR-TKIs as third- and fourth-line regimens. OUTCOMES: The patients achieved partial responses to EGFR-TKIs according to radiologic findings. However, second-line ALK-TKI therapy was ineffective in cases 1 and 2. LESSONS: Cases of NSCLC with concomitant EGFR mutation and ALK rearrangement are rare, and the selection of an optimal targeted therapy is challenging. Here, EGFR-TKI appeared to yield better outcomes than ALK-TKI in patients with NSCLC who harbored EGFR/ALK co-alterations.


Assuntos
Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
17.
Thorac Cancer ; 9(7): 856-864, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29761660

RESUMO

BACKGROUND: In cases of EGFR-tyrosine kinase inhibitor (TKI) failure, re-biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re-biopsy is challenging because of several hurdles. We assessed the feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC) patients in real-world clinical practice. METHODS: We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR-TKIs at a single tertiary hospital in Korea between January 2014 and December 2016. Re-biopsy specimens included small biopsy, surgical tissue, or liquid-based cytology. EGFR mutation was tested using peptide nucleic acid-mediated clamping PCR. RESULTS: Of the 230 NSCLC patients that experienced progression after EGFR-TKI therapy, 105 (45.7%) underwent re-biopsy. Re-biopsy was successfully performed in 94 (89.5%) patients, and 11 patients were diagnosed with no malignancy. The complication rate was 8.6%, including seven cases of pneumothorax. EGFR mutation testing was performed on 75 patients using re-biopsy specimens. Of the 57 patients who had sensitizing mutations at diagnosis, T790M mutations were found in 19 (33.3%), while 38 (66.7%) had no T790M mutation. Multivariate analysis showed that the re-biopsy group was younger (P = 0.002) and exhibited a previous response to EGFR-TKIs (P < 0.001). CONCLUSION: Re-biopsy in advanced NSCLC is feasible in real world clinical practice, particularly in younger patients and those who achieved a previous response to EGFR-TKIs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Proteínas Quinases/administração & dosagem , Idoso , Biópsia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos
18.
Korean J Gastroenterol ; 59(4): 303-7, 2012 04.
Artigo em Coreano | MEDLINE | ID: mdl-22544028

RESUMO

Cytomegalovirus (CMV) colitis is common among immunocompromised patients, and often diagnosed by pathologic confirmation because it is associated with a diverse spectrum of clinical and endoscopic features. However, Crohn's disease has no definitive diagnostic criteria, but longitudinal ulcers and cobble stone appearance are accepted as typical endoscopic features of Crohn's disease. An 83 year-old male with a history of radiotherapy for hypopharyngeal cancer visited our hospital with a complaint of melena for 1 week. His colonoscopic exam showed multiple longitudinal ulcers along the entire colon. Most of the ulcers were longer than 4 cm, these endoscopic findings were suspected as typical endoscopic features of Crohn's disease. Pathologic reports revealed multiple inclusion bodies with CMV on immunohistochemistry. He was finally diagnosed as having CMV colitis, and received a 3 week-course of intravenous ganciclovir. A colonoscopic follow-up showed complete healing of the multiple longitudinal ulcers, and he is doing well now without further treatment.


Assuntos
Colite/diagnóstico , Infecções por Citomegalovirus/diagnóstico , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Colite/etiologia , Colite/patologia , Colonoscopia , Doença de Crohn/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/patologia , Ganciclovir/uso terapêutico , Humanos , Imuno-Histoquímica , Injeções Intravenosas , Masculino , Tomografia Computadorizada por Raios X
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