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INTRODUCTION: Data on factors related to mortality in patients with bronchiectasis exacerbation are insufficient. Computed tomography (CT) can measure the pectoralis muscle area (PMA) and is a useful tool to diagnose sarcopenia. This study aimed to evaluate whether PMA can predict mortality in patients with bronchiectasis exacerbation. METHODS: Patients hospitalized due to bronchiectasis exacerbation at a single center were retrospectively divided into survivors and non-survivors based on 1-year mortality. Thereafter, a comparison of the clinical and radiologic characteristics was conducted between the two groups. RESULTS: A total of 66 (14%) patients died at 1 year. In the multivariate analysis, age, BMI <18.4 kg/m2, sex-specific PMA quartile, ≥3 exacerbations in the previous year, serum albumin <3.5 g/dL, cystic bronchiectasis, tuberculosis-destroyed lung, and diabetes mellitus were independent predictors for the 1-year mortality in patients hospitalized with bronchiectasis exacerbation. A lower PMA was associated with a lower overall survival rate in the survival analysis according to sex-specific quartiles of PMA. PMA had the highest area under the curve during assessment of prognostic performance in predicting the 1-year mortality. The lowest sex-specific PMA quartile group exhibited higher disease severity than the highest quartile group. CONCLUSIONS: CT-derived PMA was an independent predictor of 1-year mortality in patients hospitalized with bronchiectasis exacerbation. Patients with lower PMA exhibited higher disease severity. These findings suggest that PMA might be a useful marker for providing additional information regarding prognosis of patients with bronchiectasis exacerbation.
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Bronquiectasia , Progressão da Doença , Músculos Peitorais , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Bronquiectasia/mortalidade , Bronquiectasia/diagnóstico por imagem , Idoso , Músculos Peitorais/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Hospitalização , Sarcopenia/diagnóstico por imagem , Sarcopenia/mortalidade , Sarcopenia/diagnóstico , PrognósticoRESUMO
BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. METHODS: This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. RESULTS: This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. CONCLUSION: High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Derrame Pleural Maligno , Derrame Pleural , Humanos , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/terapia , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/uso terapêutico , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Receptores ErbB/genética , Derrame Pleural/induzido quimicamente , Derrame Pleural/diagnóstico , Derrame Pleural/tratamento farmacológico , MutaçãoRESUMO
The data regarding pulmonary artery stump thrombosis (PAST) after lung cancer surgery are insufficient. The aim of the present study was to evaluate the incidence, clinical characteristics, and prognosis of PAST. We retrospectively investigated the incidence and clinical characteristics of PAST among patients who underwent lung resection for lung cancer at 2 institutions. We compared the clinical parameters between PAST and pulmonary embolism (PE) and examined the clinical course of patients with PAST. Of the 1885 patients, PAST was found in 36 patients (1.9%). Right lower lobectomy (nâ =â 13) and middle-lower bilobectomy (nâ =â 9) were the most common types of surgery. The median time interval from lung resection to the detection of PAST was 3.8 months. Immobilization and a history of cerebrovascular disease were not observed in the PAST group. Most of the patients with PAST (91.7%) were diagnosed incidentally, whereas many patients with PE (75.9%) were symptomatic at the time of diagnosis. During the follow-up, one patient (2.8%) had contralateral PE complications. However, no patients in the PAST group experienced pulmonary thromboembolism-related in-hospital death or adverse outcomes. There was no difference in the prognosis of patients with PAST according to the administration of anticoagulation. PAST was rarely detected in lung cancer patients on follow-up chest computed tomography after lung resection. Patients with PAST were asymptomatic in most cases and had relatively favorable clinical outcomes. However, these patients are at risk of contralateral PE, despite its rarity.
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Neoplasias Pulmonares , Embolia Pulmonar , Trombose Venosa , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicações , Artéria Pulmonar/cirurgia , Mortalidade Hospitalar , Centros de Atenção Terciária , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Trombose Venosa/etiologia , Pulmão , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/diagnósticoRESUMO
INTRODUCTION: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC). METHODS: In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. The association between 176 polymorphisms of lipid metabolism pathway genes and the clinical outcomes of NSCLC patients was analyzed. RESULTS: Among the polymorphisms investigated, ACADSB rs10902859G>A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G>A was located in the repressed region and had strong linkage disequilibrium (D' = 1.00 and r2 = 0.94), with rs12220683G>C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G>C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30-0.94, p = 0.03; aHR = 0.37, 95% CI = 0.15-0.89, p = 0.03; and aHR = 0.47, 95% CI = 0.29-0.75, p = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (p = 3 × 10-5). CONCLUSION: These results suggest that ACADSB rs12220683G>C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/genética , Metabolismo dos Lipídeos/genética , Genótipo , Polimorfismo de Nucleotídeo Único , PrognósticoRESUMO
BACKGROUND: Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC. Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions. METHODS: We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC. RESULTS: Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26-0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38-2.57, P < 0.001). CINP rs762105A>G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23-0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47-2.82, P < 0.001). ChIP-quantitative polymerase chain reaction and luciferase assay confirmed that the two SNPs were located in the active promoter regions and influenced the promoter activity of each gene. CONCLUSION: To summarize, among SNPs selected using ChIP-seq in promoter regions with high peaks in both NeuroD1 and H3K4me3, RNF145 rs2043268A>G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Histonas/genética , Histonas/metabolismo , Histonas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genéticaRESUMO
High-level MET amplification (METamp) is a primary driver in â¼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14.3 months (95% CI, 2.8-not estimable). In exploratory biomarker analyses, focal METamp, RB1 wild-type, MYC diploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pirimidinas , Biópsia LíquidaRESUMO
Background: Patients with bronchiectasis commonly experience disease exacerbations, which cause significant morbidity and mortality. However, data regarding the clinical features of bronchiectasis patients hospitalized with hemoptysis are scarce. Methods: We retrospectively collected the data of patients with bronchiectasis-associated hospitalization at a tertiary referral center in Korea, and classified them into the hemoptysis and infective exacerbation (IE) groups. The presence of hemoptysis was defined as a volume of expectorated blood larger than 10 mL per 24 hours. The clinical, radiological, and laboratory parameters were compared between the two groups. Results: Patients were classified into the hemoptysis [267 (54.5%)] and IE [223 (45.5%)] groups. Among the 44 patients of the hemoptysis group, 37 (84.1%) presented with hemoptysis than with IE at the recurrent episode. The hemoptysis group had a significantly lower 30-day mortality than that of the IE group. Previous pulmonary tuberculosis (TB), mycetoma, and bronchial artery hypertrophy were independently associated with the hemoptysis group. In contrast, male sex, poor performance status, colonization of Pseudomonas aeruginosa, ≥3 involved lobes, cystic bronchiectasis, and emphysema were inversely associated with the hemoptysis group. The absence of hemoptysis was one of the independent predictors of 30-day mortality in patients with bronchiectasis-associated hospitalization. Conclusions: In Korea, bronchiectasis patients hospitalized with hemoptysis exhibit a distinct phenotype, and are more likely to have previous pulmonary TB, mycetoma, and bronchial artery hypertrophy. Hemoptysis is associated with a lower risk of short-term mortality compared to IE in bronchiectasis-associated hospitalization.
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BACKGROUND: Necroptosis is a regulated inflammatory cell death which plays a significant role in cancer development and progression. In this study, we evaluated whether genetic variants in key regulators of necroptosis may affect survival outcome of non-small cell lung cancer (NSCLC) patients after surgical resection. METHODS: A total of 674 patients who underwent curative surgery were included. Fifteen genetic variants in key regulators of necroptosis (RIPK1, RIPK3, and MLKL) were selected. The association of these variants with survival outcomes was evaluated. RESULTS: Two variants, RIPK1 rs17548629C > T and MLKL rs877375G > C, were associated with better overall survival and disease-free survival in multivariate analyses. When the patients were divided according to histology, the associations were significant only in adenocarcinoma, but not in squamous cell carcinoma. RIPK1 rs17548629 C-to-T change was associated with significantly increased luciferase activity by modulating the binding of miR-642a. Promoter assays showed a significantly increased promoter activity in MLKL rs877375C allele compared to G allele. Consistently, the mRNA expression level of RIPK1 and MLKL showed significant positive correlation with RIPK1 rs17548629C-to-T and MLKL rs877375G-to-C changes. CONCLUSION: Two genetic variants in key regulators in necroptosis, RIPK1 rs17548629C > T and MLKL rs877375G > C, may be used as biomarkers to predict survival outcomes in surgically resected NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Necroptose/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , PrognósticoRESUMO
Non-expandable lung (NEL) often occurs during pleural fluid drainage in patients with malignant pleural effusion (MPE). However, data regarding the predictors and prognostic impact of NEL on primary lung cancer patients with MPE receiving pleural fluid drainage, compared to malignant pleural mesothelioma (MPM), are limited. This study was aimed to investigate the clinical characteristics of lung cancer patients with MPE developing NEL following ultrasonography (USG)-guided percutaneous catheter drainage (PCD) and compare the clinical outcomes between those with and without NEL. Clinical, laboratory, pleural fluid, and radiologic data and survival outcomes of lung cancer patients with MPE undergoing USG-guided PCD were retrospectively reviewed and compared between those with and without NEL. Among 121 primary lung cancer patients with MPE undergoing PCD, NEL occurred in 25 (21%). Higher pleural fluid lactate dehydrogenase (LDH) levels and presence of endobronchial lesions were associated with development of NEL. The median time to catheter removal was significantly extended in those with NEL compared to those without (P = .014). NEL was significantly associated with poor survival outcome in lung cancer patients with MPE undergoing PCD, along with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), the presence of distant metastasis, higher serum C-reactive protein (CRP) levels, and not receiving chemotherapy. NEL developed in one-fifth of lung cancer patients undergoing PCD for MPE and was associated with high pleural fluid LDH levels and the presence of endobronchial lesions. NEL may negatively affect overall survival in lung cancer patients with MPE receiving PCD.
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Neoplasias Pulmonares , Derrame Pleural Maligno , Humanos , Derrame Pleural Maligno/diagnóstico por imagem , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/terapia , Estudos Retrospectivos , Neoplasias Pulmonares/complicações , Cateteres Cardíacos , Drenagem , PulmãoRESUMO
BACKGROUND: Computed tomography (CT) is the mainstay imaging modality for suspected pleural malignancy. Tuberculous pleural effusion (TPE) can present with various pleural abnormalities. However, few studies have evaluated the different characteristics of pleural abnormalities on chest CT between TPE and malignant pleural effusion (MPE). METHODS: Pleural abnormalities on contrast-enhanced CT in 277 and 289 patients with confirmed TPE and MPE diagnoses, respectively, were retrospectively assessed and compared between the two groups. Discriminating factors and diagnostic performance for MPE were evaluated using multivariate analysis and receiver operating characteristic curves. RESULTS: Focal pleural thickening was present in 44 (16%) cases of TPEs and 202 (70%) of MPEs. Further characterization of focal pleural thickening showed that MPEs had a significantly greater number, larger maximal thickness, and more nodular contour form, compared to TPEs. On the other hand, diffuse and circumferential pleural thickening were significantly more common in TPEs. In multivariate analysis, independent predictors for MPE included focally thickened pleurae ≥7, maximum thickness ≥6 mm, nodular contour pattern, and the absence of diffuse pleural thickening. Out of all the individual or combined predictors for MPE, the presence of any one of the three sub-parameters of focal pleural thickening provided the best diagnostic yield with 66% sensitivity and 92% specificity. CONCLUSION: Although focal pleural thickening in TPE mimics that in MPE, the features of MPE are significantly different from those of TPE in terms of size, number, and contour. These different characteristics may help differentiate MPE from TPE in patients with suspected MPE.
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Derrame Pleural Maligno , Derrame Pleural , Tuberculose Pleural , Humanos , Derrame Pleural Maligno/patologia , Estudos Retrospectivos , Tuberculose Pleural/diagnóstico por imagem , Derrame Pleural/diagnóstico , Tomografia Computadorizada por Raios X , Diagnóstico DiferencialRESUMO
BACKGROUND: Data regarding the clinical characteristics and treatment outcomes of patients with community-acquired pneumonia (CAP) and bronchiectasis (BE) are rare. This study aims to elucidate the clinical relevance of BE in patients with CAP. METHODS: Patients hospitalized with CAP in a single center were retrospectively analyzed and divided into significant BE (BE with ≥ 3 lobes or cystic BE on computed tomography) and control groups. Clinical and microbiological characteristics were compared between the two groups. RESULTS: In the final analysis, 2112 patients were included, and 104 (4.9%) had significant BE. The significant BE group exhibited a higher prevalence of sputum production, dyspnea, and complicated parapneumonic effusion or empyema than the control group. Pseudomonas aeruginosa was more frequently isolated in the significant BE group than in the control group, whereas Mycoplasma pneumoniae was less commonly identified. Length of hospital stay (LOS) was significantly longer in the significant BE group than the control group (12 [8-17] days vs. 9 [6-13] days, p < 0.001). In contrast, 30-day and in-hospital mortality rates did not significantly differ between the two groups. Furthermore, significant BE was an independent predictor of prolonged hospitalization in two models based on CURB-65 and pneumonia severity index. CONCLUSIONS: Significant BE occurred in approximately 5% of patients with CAP and was more likely to be associated with sputum, dyspnea, complicated parapneumonic effusion or empyema, and isolation of P. aeruginosa. Significant BE was an independent predictor of LOS in patients with CAP.
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Bronquiectasia , Infecções Comunitárias Adquiridas , Empiema , Derrame Pleural , Pneumonia , Humanos , Estudos Retrospectivos , Relevância Clínica , Pneumonia/complicações , Pneumonia/epidemiologia , Pneumonia/tratamento farmacológico , Derrame Pleural/tratamento farmacológico , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Bronquiectasia/complicações , Bronquiectasia/epidemiologiaRESUMO
BACKGROUND: Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small-cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. METHODS: In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. RESULTS: The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix-loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10-6 ). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). CONCLUSION: These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genéticaRESUMO
BACKGROUND: Despite therapeutic advances, lung cancer prognosis remains poor. Loss of heterozygosity (LOH) in the 3p21 region is well documented in lung cancer, but the specific causative genes have not been identified. MATERIALS AND METHODS: Here, we aimed to examine the clinical impact of miR-135a, located in the 3p21 region, in lung cancer. miR-135a expression was assessed using quantitative real-time polymerase chain reaction. LOH was analyzed at microsatellite loci D3S1076 and D3S1478, and promoter methylation status was determined by pyrosequencing of resected samples of primary non-small-cell lung cancer (NSCLC). The regulation of telomerase reverse transcriptase (TERT) was evaluated in lung cancer cells H1299 by luciferase report assays after treatment with miR-135a mimics. RESULTS: miR-135a was significantly downregulated in squamous cell cancer (SCC) tumor tissues compared to normal tissues (p = 0.001). Low miR-135a expression was more frequent in patients with SCC (p = 2.9 × 10-4 ) and smokers (p = 0.01). LOH and hypermethylation were detected in 27.8% (37/133) and 17.3% (23/133) of the tumors, respectively. Overall, 36.8% (49/133) of the NSCLC cases harbored either miR-135a LOH or promoter hypermethylation. The frequencies of LOH and hypermethylation were significantly associated with SCCs (p = 2 × 10-4 ) and late-stage (p = 0.04), respectively. MiR-135a inhibited the relative luciferase activity of psiCHECK2-TERT-3'UTR. CONCLUSION: These results suggest that miR-135a may act as a tumor suppressor to play an important role in lung cancer carcinogenesis, which will provide a new insight into the translational value of miR-135a. Further large-scale studies are required to confirm these findings.
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Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Genes Supressores de Tumor , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
OBJECTIVE: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. METHODS: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. RESULTS: Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36-0.97, p = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09-1.91, p = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. CONCLUSION: This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Pemetrexede/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Código das Histonas , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
This study was conducted to investigate the relationship between genetic variants in LKB1/AMPK/mTOR pathway and treatment outcomes of patients with non-small cell lung cancer (NSCLC) treated with chemotherapy. A total of 379 patients with NSCLC who underwent first-line paclitaxel-cisplatin chemotherapy was enrolled. The associations between 19 single nucleotide variants (SNVs) in the LKB1/AMPK/mTOR pathway and the chemotherapy response and overall survival (OS) were analyzed. Among the SNVs analyzed, AKT1 rs2494750G>C and TSC1 rs2809244C>A were associated with clinical outcomes after chemotherapy in multivariate analyses. The AKT1 rs2494750G>C was significantly associated with a better response to chemotherapy (adjusted odds ratio [aOR]: 1.92, 95% confidence interval [CI]: 1.02-3.62, p = 0.04). The TSC1 rs2809244C>A were significantly associated with better OS (adjusted hazard ratio [aHR]: 0.79, 95% CI: 0.62-0.99, p = 0.04). When stratified by tumor histology, AKT1 rs2494750G>C exhibited a significant association with the chemotherapy response only in adenocarcinoma and TSC1 rs2809244C>A was also significantly associated with OS only in adenocarcinoma. This result suggests that the AKT1 rs2494750G>C and TSC1 rs2809244 C>A may be useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.
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Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas Quinases Ativadas por AMP , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Adenocarcinoma/genéticaRESUMO
BACKGROUND: Life-threatening hypoxia can occur in patients with lung cancer due to bronchial obstruction. Extracorporeal membrane oxygenation (ECMO) can be used as a bridge therapy for patients with severe hypoxia not relieved by conventional mechanical treatment. However, the usefulness of chemotherapy in patients with lung cancer receiving ECMO therapy is not well known. CASE SUMMARY: A 53-year-old man visited the emergency room with worsening dyspnea for 1 mo. A series of imaging and diagnostic tests were performed, and stage IIIB (cT4N2M0) lung cancer was eventually diagnosed. On hospital day 3, he experienced dyspnea and hypoxia that was not relieved with oxygen support via a high-flow nasal cannula. ECMO was initiated because his respiratory condition did not improve even with mechanical ventilation. The patient then underwent gemcitabine/cisplatin chemotherapy without dose reduction while on ECMO. After two cycles of chemotherapy, there was a decrease in the size of the primary tumor in the right main bronchus. After the completion of concurrent chemoradiotherapy, a computed tomography scan revealed further improvement in the right main bronchus narrowing. Eight months after a lung cancer diagnosis, the patient did well without any dyspnea. CONCLUSION: ECMO is a potential bridge therapy for respiratory failure in patients with central airway obstruction secondary to lung cancer.
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Hemoptysis is a common cause of emergency department (ED) visits. There is little data about the role of systemic hypertension as a cause of hemoptysis. The aim of this study was to evaluate the association between systemic blood pressure and the unknown etiology of hemoptysis. This retrospective study included consecutive patients who visited the ED owing to hemoptysis and underwent a chest computed tomography between January 2011 and June 2021. Details of the initial blood pressure at the ED visit were compared between two groups with identified and unidentified causes of hemoptysis. In total, 1105 adult patients were included. The etiology of hemoptysis was identified in 1042 patients (94.3%) and remained unidentified in 63 patients (5.7%). The percentage of patients with severe hypertension was significantly higher in patients with unidentified causes of hemoptysis than in those with identified causes (35% vs. 11%, p < 0.001). In multivariate analysis, age, ever-smoker, and initial systolic blood pressure were significantly associated with hemoptysis of unidentified causes. Although further studies are needed, our findings suggest a possible association between high blood pressure and cryptogenic hemoptysis.
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Differential leukocyte counts of pleural fluid are routinely recommended for the early diagnosis and management of exudative pleural effusions. Rapid automated cellular analysis agrees strongly with standard manual microscopic counts and has become a reality in many clinical laboratories. However, discordant results sometimes observed between automated and manual analyses raise concern about using automated analysis to aid prompt differential diagnosis. This study aimed to evaluate the real-world disagreement between automated and manual leukocyte analyses in exudative pleural effusions and to investigate whether the discordant results occur in specific cellular ranges or randomly. We conducted a retrospective study of patients who were diagnosed with parapneumonic pleural effusions (PPE), tuberculous pleural effusions (TPE), and malignant pleural effusions (MPE) between September 2018 and December 2020. Differential and predominant leukocyte counts were performed using an automated XN-350 analyzer with a two-part differential count consisting of polymorphonuclear (PMN) and mononuclear (MN) leukocytes and a manual method with Wright-stained cytospin slides. We compared the two methods on cases of 109 PPEs, 50 TPEs, and 116 MPEs. Although the overall correlation between the two methods for differential leukocyte counts was excellent, there were etiologic variations; MPEs showed a lower correlation compared to PPEs and TPEs. Automated-PMN predominance almost corresponded to manual cytospin-neutrophilic predominance. In contrast, ~10% of the automated-MN predominance did not correspond with the cytospin-lymphocytic predominance. These discrepancies occurred most in the automated-MN% range of 51% to 60%, followed by 61% to 70%. The PMN% range ≥50% and <30% on the automated analysis reliably corresponds to the neutrophilic and lymphocytic predominance, respectively. However, the MN% range of 51% to 70% may not coincide with lymphocytic predominance on manual cytospin analysis. This range leaves the potential cause of exudative pleural effusions open.
Assuntos
Derrame Pleural , Humanos , Contagem de Leucócitos , Leucócitos/patologia , Linfócitos/patologia , Derrame Pleural/diagnóstico , Derrame Pleural/patologia , Estudos RetrospectivosRESUMO
Background: We aimed to evaluate the efficacy of postoperative adjuvant pemetrexed plus cisplatin (Pem-Cis) in pathologic stage IB-IIIA lung adenocarcinoma (LUAD) patients. Methods: A prospective, phase II study was performed in seven institutions in South Korea. Patients with completely resected stage IB-IIIA LUAD received pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2). Adjuvant treatments were administered every 3 weeks for 4 cycles. The primary endpoint was to prove the Pem-Cis's superiority in terms of 2-year disease-free survival rate (DFSR) compared with historical control without adjuvant chemotherapy (50%). Results: Between August 2015 and February 2018, 105 patients were enrolled in this study. Approximately 31.4% (n=33), 43.8% (n=46), and 24.8% (n=26) of patients had pathologic stage IB, II, and IIIA, respectively. Most of the patients underwent lobectomy (n=98, 93.3%). Moreover, 41.1% and 12.1% of the patients had epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase rearrangement. Four cycles of Pem-Cis were administered in 99 patients (94.3%). At a median follow-up of 57.7 months, the 2-year DFSR was 78.1%. Multivariable analysis showed that pathologic stage IIIA and EGFR mutation were significant risk factors for DFS. Grade 3 adverse events occurred in 10 patients (9.5%), and leukopenia (n=3, 2.9%) was the most common adverse event. Conclusions: Adjuvant Pem-Cis is superior to historical control without adjuvant treatment in terms of 2-year DFSR; the proportion of patients with stage IB and driver mutations were higher than that of patients in previous trials. Pem-Cis showed favorable tolerability as adjuvant chemotherapy (clinicaltrial.gov; Identifier: NCT02498860).