To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC).
Identification of differentially ...methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples.
A methylation panel of 6 genes (
, and
) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of
, and
refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with
methylation, showed poor outcomes.
Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis.
.
Primary tracheobronchial schwannomas are extremely rare. Surgical treatment has been the first choice for these benign tumours due to the substantial residual rates and recurrences after ...bronchoscopic resection. In addition, there has been limited information on bronchoscopic removal of endobronchial schwannomas. We describe two cases of large tracheal and bronchial schwannomas that were completely and successfully resected by snare electrocautery, insulation‐tipped knife, and argon plasma coagulation under rigid bronchoscopy. These cases highlight that rigid bronchoscopic treatment with these multiple instruments can be a good treatment option for endotracheal or endobronchial schwannomas.
Primary tracheobronchial schwannomas are extremely rare. Surgical treatment has been the first choice for these benign tumors due to the substantial residual rates and recurrences. The preset study suggests that rigid bronchoscopic treatment with multiple instruments such as snare electrocautery, insulation‐tipped knife, and argon plasma coagulation can be a good option for tracheobronchial schwannomas.
A blood‐based approach such as circulating tumor DNA remains challenging in diagnosis for early‐stage disease. Bronchial washing (BW) is a minimally invasive procedure that yields fluids that may ...contain tumor DNA. Therefore, we prospectively enrolled 12 patients with early‐stage non‐small cell lung cancer without endoscopically visible tumors. Somatic mutations were analyzed using ultra‐deep next‐generation sequencing in 48 paired specimens (primary tumor tissue, normal tissue, BW supernatant, and BW precipitate). In primary tumors, 130 missense mutations/indels (5–16 per patient) and 20 driver mutations (0–3 per patient) were found. Concordance of driver mutations between BW fluids and primary tumors was 95.0%. The allele frequencies for missense mutations/indels in BW supernatants significantly correlated with those in primary tumors and were higher than those in BW precipitates. These findings suggest that BW supernatants are reflective of tumor‐associated mutations and could be used for early‐stage lung cancer diagnosis.
摘要
早期疾病的诊断中，难以采用循环肿瘤 DNA 等以血液为基础的诊断方法。支气管冲洗 (BW) 是一种微创手术，可产生可能含有肿瘤 DNA 的冲洗液。因此，本研究前瞻性分析了 12 例内镜下无可见肿瘤的早期非小细胞肺癌患者临床资料。采用超深新一代测序技术对 48 对标本(原发肿瘤组织、正常组织、BW 上清液和 BW 沉淀物)进行了体细胞突变分析。在原发性肿瘤中，发现 130 处错义突变/插入缺失(每位患者 5‐16 处)和 20 处驱动突变(每位患者 0‐3处)。BW 液与原发肿瘤的驱动突变一致性为 95.0%。BW 上清液中错义突变/插入缺失的等位基因频率与原发肿瘤的等位基因频率显著相关，且高于 BW 沉淀物。结果表明，BW 上清液可反映出肿瘤相关突变，可用于早期肺癌的诊断。
The potential of circulating tumor DNA (ctDNA) detection in early stage lung cancer is explored. This study investigated whether bronchial washing, a minimally invasive procedure that yields fluids that may contain ctDNA, can reflect genetic profiles of primary tumors using next‐generation sequencing.
Various studies have reported that the neutrophil-to-lymphocyte ratio in the serum (sNLR) may serve as a cost-effective and useful prognostic factor in patients with various cancer types. However, no ...study has reported the prognostic impact of the NLR in malignant pleural effusion (MPE). To address this gap, we investigated the clinical impact of NLR as a prognostic factor in MPE (mNLR) and a new scoring system that use NLRs in the serum and MPE (smNLR score) in lung cancer patients.
We retrospectively reviewed all of the patients who were diagnosed with lung cancer and who presented with pleural effusion. To maintain the quality of the study, only patients with malignant cells in the pleural fluid or tissue were included. The patients were classified into three smNLR score groups, and clinical variables were investigated for their correlation with survival.
In all, 158 patients were classified into three smNLR score groups as follows: 84 (53.2%) had a score of 0, 58 (36.7%) had a score of 1, and 16 (10.1%) had a score of 2. In a univariate analysis, high sNLR, mNLR, and increments of the smNLR score were associated with shorter overall survival (p < 0.001, p = 0.004, and p < 0.001, respectively); moreover, age, Eastern Cooperative Oncology Group performance status (ECOG PS), histology, M stage, hemoglobin level, albumin level, and calcium level were significant prognostic factors. A multivariable analysis confirmed that ECOG PS (p < 0.001), histology (p = 0.001), and smNLR score (p < 0.012) were independent predictors of overall survival.
The new smNLR score is a useful and cost-effective prognostic factor in lung cancer patients with MPE. Although further studies are required to generalize our results, this information will benefit clinicians and patients in determining the most appropriate therapy for patients with MPE.
Minimal (< 10 mm thick) pleural effusion (PE) may represent an early phase of malignant PE, but its clinical relevance has rarely been studied. Therefore, we examined the proportion of minimal PE in ...patients with non-small-cell lung cancer (NSCLC) and its impact on survival. We also considered possible accumulation mechanisms in our data set.
On the basis of PE status from chest computed tomography scans at diagnosis, 2,061 patients were classified into three groups: no PE, minimal PE, and malignant PE. Twenty-one variables associated with four factors-patient, stage migration, tumor, and treatment-were investigated for correlation with survival.
Minimal PE presented in 272 patients (13.2%). Of 2,061 patients, the proportion of each stage was the following: 5.2% stage I, 10.9% stage II, 13.2% stage IIIA, 23.8% stage IIIB, and 13.9% stage IV. Minimal PE correlated significantly with shorter survival time than did no PE (median survival time, 7.7 v 17.7 months; log-rank P < .001), even after full adjustment with all variables (adjusted hazard ratio, 1.40; 95% CI, 1.21 to 1.62). Prognostic impact of minimal PE was higher in early versus advanced stages (Pinteraction = .001). In 237 patients (87.8%) with minimal PE, pleural invasion or attachment as a direct mechanism was observed, and it was an independent factor predicting worse survival (P = .03).
Minimal PE is a commonly encountered clinical concern in staging NSCLCs. Its presence is an important prognostic factor of worse survival, especially in early-stage disease.
Recent advances in mitochondrial biogenesis have provided the emerging recognition that mitochondria do much more than 'simply providing energy for cellular function'. Currently, a constantly ...improving understanding of the mitochondrial structure and function has been providing valuable insights into the contribution of defects in mitochondrial metabolism to various human diseases, including chronic obstructive pulmonary disease and lung cancer. The growing interest in mitochondria research led to development of new biomedical fields in the two main smoking-related lung diseases. However, there is considerable paucity in our understanding of mechanisms by which mitochondrial dynamics regulate lung diseases. In this review, we will discuss our current knowledge on the role of mitochondrial dysfunction in the pathogenesis of chronic obstructive pulmonary disease and non-small-cell lung cancer.
Malignant pleural effusions (MPEs) are the second leading cause of exudative pleural effusions after parapneumonic effusions. In the vast majority of cases, a MPE signifies incurable disease ...associated with high morbidity and mortality. Considerable advances have been made for the diagnosis of MPEs, through the development of improved methods in the specialized cytological and imaging studies. The cytological or histological confirmation of malignant cells is currently important in establishing a diagnosis. Furthermore, despite major advancements in cancer treatment for the past two decades, management of MPE remains palliative. This article presents a comprehensive review of the medical approaches for diagnosis and management of MPE.
Abstract Objectives Chronic necrotizing pulmonary aspergillosis (CNPA) is uncommon, and the optimal therapeutic regimen has not been established. In a retrospective cohort study, we investigated the ...clinical characteristics and treatment outcomes of patients with CNPA. Methods We reviewed the medical records of all patients who had been diagnosed with CNPA at our institution over the last 10 years. Results Forty-three patients were identified. Their median age was 60 years (interquartile range (IQR) 45–65 years), and 34 (79%) of the patients were men. The most common underlying lung disease was pulmonary tuberculosis ( n = 40, 93%). After CNPA was diagnosed, all patients were treated with antifungal drugs, including oral itraconazole ( n = 39, 91%) or intravenous amphotericin B ( n = 4, 9%). Seventeen (40%) patients discontinued therapy early (<3 months), 14 patients due to death and three to loss of follow-up. Twenty-six (60%) patients received oral itraconazole at a daily dose of 200–400 mg for more than 3 months. The median treatment duration was 6 months (IQR 6–12 months). In these 26 patients, clinical improvement was observed in 15 (58%) and radiological improvement was observed in 11 (42%). Ten (38%) patients showed no improvement. Twenty-two (51%) patients died, including 18 (42%) CNPA-related deaths, during a median follow-up of 15 months (IQR 2.5–32 months). The median survival time was 62 months. Conclusions CNPA is difficult to treat and often has a poor outcome. Further studies with more patients are needed to identify the optimal therapy for patients with CNPA.
The optimum sequence of bronchial brushing and washing for diagnosing peripheral lung cancer, defined as an invisible endobronchial tumour, is not clear and requires further study. We prospectively ...obtained washing samples after brushing in patients with peripheral lung tumours during non-guided flexible bronchoscopy (FB) to investigate the diagnostic yield of these samples and conducted a retrospective review of the prospectively collected data. The study included 166 patients who met the inclusion criteria. The overall diagnostic yield of bronchial brushing and washing for peripheral lung cancer was 52.4%. The diagnostic yields of brushing and washing were 37.3% and 46.4%, respectively, and that of washing was superior according to McNemar's test (p = 0.017, κ = 0.570). Furthermore, washing was diagnostic, whereas brushing was not, in 15.1% of all cases. Comparison of positive washing cytology (brushing) with the respective pathological diagnosis yielded a concordance rate of 88.3% (90.3%), with κ = 0.769 (0.801) (p < 0.001). Performing washing after brushing during non-guided FB is a very safe, cost-effective procedure that may help improve the diagnostic yield in patients with suspected peripheral lung cancer. Our information will also benefit clinicians performing diagnostic bronchoscopy in patients with suspected peripheral lung cancer when fluoroscopic guidance or advanced bronchoscopy techniques are not available.
Crizotinib is an oral selective small-molecular tyrosine kinase inhibitor (TKI) that suppress the activity of anaplastic lymphoma kinase (ALK) and ROS1 kinases, as well as mesenchymal-epithelial ...transition. The cumulative clinical trials in patients with advanced ALK- or ROS1-rearrangement NSCLC indicate that crizotinib has significant antitumor activity and a tolerable safety profile, with mild or moderate adverse events of visual disorders, diarrhea, nausea, and vomiting. As with other TKIs, however, the occurrence of crizotinib-related interstitial lung disease (crizotinib-ILD) remains a major clinical dilemma that can lead to the permanent discontinuation of TKI during cancer treatment. When there is no suitable alternative therapy for patients who develop crizotinib-ILD, some clinicians have reported successful crizotinib retreatment in cases of ALK-rearrangement NSCLC. Unfortunately, there are no specific guidelines for the treatment or retreatment of TKI-related ILD. We herein report the first successful crizotinib retreatment after crizotinib-ILD in a patient with ROS1-rearranged NSCLC, and suggest a retreatment strategy after crizotinib-ILD based on a literature review.
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