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1.
J Thorac Dis ; 16(5): 3096-3106, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38883671

ABSTRACT

Background: Advances in minimally invasive surgery and drainage systems have caused earlier chest-tube-removal. This retrospective study aimed to assess the safety of early chest tube removal using the institution's new criteria 6 hours after thoracic surgery. Methods: Elective thoracic surgery patients from 2017 to 2023 were reviewed for meeting or not meeting the newer institutional requirement for early chest tube removal; (I) no air leak detected under the digital drainage device observation; (II) no fluid drainage of ≥100 mL/h; (III) no ≥3 combined risks [male, chronic obstructive pulmonary disease (COPD), body mass index (BMI) of <18.5 kg/m2, severe pleural adhesion, upper lobe lobectomy, or left upper division segmentectomy]. The incidence of adverse events, including chest tube replacement, subcutaneous tube placement, and postoperative thoracentesis, were investigated for 1 month postoperatively. Perioperative outcomes and factors involved in conventional chest tube removal were also assessed. Results: Of the 942 patient charts reviewed, 244 (25.9%) met the criteria for chest tube removal within 6 hours postoperatively. This patient group did not experience adverse events. They also demonstrated shorter postoperative hospital stay (4 vs. 6 days, P<0.001), and lesser postoperative complications (7.4% vs. 25.6%, P<0.001) compared to those for whom early chest tube removal was not done. A correlation with thoracotomy, COPD, and steroid and/or immunosuppressant use was observed for patients in the conventional chest tube removal group. Conclusions: Early chest tube removal after 6 postoperative hours was deemed safe for a selected group of patients who met the criteria for early chest tube removal. This study would support the potential expansion of our early removal criteria.

2.
Sci Rep ; 13(1): 1850, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36725903

ABSTRACT

There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Biopsy/adverse effects , Biopsy/methods , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Prospective Studies , Surgical Instruments
3.
Mol Clin Oncol ; 16(1): 22, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34909200

ABSTRACT

Minichromosome maintenance (MCM) protein deregulation is associated with tumor formation, progression and malignant transformation. MCM2 is frequently expressed during premalignant lung cell proliferation and is a sensitive marker for the early detection of pulmonary malignant lesions. The present study was undertaken to investigate whether MCM2 expression is of clinical and prognostic value in patients who have undergone lung adenocarcinoma resection. Between January 2009 and December 2010, 102 consecutive patients underwent complete pulmonary resection (involving lobectomy or more extensive resection) for lung adenocarcinoma at St. Marianna Medical University Hospital (Kanagawa, Japan). Among those, 73 patients, who had a final pathological diagnosis of lung adenocarcinoma measuring ≥10 mm, were enrolled in the present study. High MCM2 expression was found in 35 patients (48.0%). Univariate analysis of the overall survival (OS) revealed that pathological stage and MCM2 expression were significant prognostic factors in lung adenocarcinoma (P<0.001 and P<0.002, respectively). Univariate analysis of the recurrence-free survival (RFS), the significant prognostic factors included pathological stage, EGFR mutation status and MCM2 expression (P<0.001, P<0.034 and P<0.003, respectively). On multivariate survival analysis, high MCM2 expression and pathological stage II-III were identified as independent strong prognostic factors (OS: HR=5.084, 95% CI: 1.715-15.080, P=0.003; RFS: HR=2.761, 95% CI: 1.090-6.998, P=0.032). Therefore, the findings of the present study demonstrated that MCM2 may serve as a potential biomarker and therapeutic target for lung adenocarcinoma.

4.
Thorac Cancer ; 13(1): 24-30, 2022 01.
Article in English | MEDLINE | ID: mdl-34811933

ABSTRACT

BACKGROUND: In this study we aimed to clarify the PD-L1 positive expression in lung adenocarcinoma, including various adenocarcinoma subtypes paying particular attention to its component. METHODS: A total of 307 lung adenocarcinoma patients who underwent lobectomy or segmentectomy, as well as systematic lymph node dissection (ND2a), from February 2008 to March 2020 at our hospital, were enrolled into the study. A final diagnosis of adenocarcinoma was obtained from the resected lung specimens of all 307 patients to determine the histological type, adenocarcinoma subtype, and component of adenocarcinoma by ethics of 5%. PD-L1 was immunohistochemically stained using the murine monoclonal antibody clone 22C3. RESULTS: When PD-L1 expression-positive was defined by tumor proportion score (TPS) ≥1%, the positive cases were 6/33 in adenocarcinoma (Ad) in situ (AIS), 2/26 in minimally invasive Ad (MIA), 12/60 in lepidic predominant Ad (LPA), 44/91 in papillary predominant Ad (PPA), 24/49 in acinar predominant Ad (APA), 23/28 in solid predominant Ad (SPA), 4/7 in micropapillary predominant Ad (MPA), and 0/13 in invasive mucinous Ad (IMA). In the high proportion group (APA, PPA, SPA, and MPA) of PD-L1 expression, SPA was the only subtype which was statistically significant when both PD-L1 expression-positive was defined by TPS ≥ 1% (p < 0.0001) and TPS â‰§ 50% (p < 0.0001). We then considered the solid component. We investigated 279 cases of the other subtype group excluding SPA. The group containing a solid component (≥5%) tended to be PD-L1 expression-positive both when defined by TPS ≥1% (p < 0.0001) and TPS â‰§50% (p = 0.0049). CONCLUSIONS: The PD-L1 expression tended to be positive when a solid component was confirmed (≥5%) in specimens of lung adenocarcinoma patients.


Subject(s)
Adenocarcinoma of Lung/metabolism , B7-H1 Antigen/metabolism , Lung Neoplasms/metabolism , Adenocarcinoma of Lung/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged
5.
Thorac Cancer ; 12(23): 3169-3176, 2021 12.
Article in English | MEDLINE | ID: mdl-34655161

ABSTRACT

BACKGROUND: The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand-1 (PD-L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. METHODS: From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD-L1 status and age, sex, stage, histological type, and prognosis were investigated. RESULTS: PD-L1-positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD-L1-positive PSC cases, two showed high PD-L1 expression in the vimentin-positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD-L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD-L1 staining in the sarcomatoid survived, whereas the other with negative PD-L1 staining did not. CONCLUSION: The present study showed that sarcomatoid carcinoma had a higher PD-L1 expression compared to non-small-cell lung cancer and that both PSC and MPM tended to exhibit PD-L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.


Subject(s)
B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Mesothelioma, Malignant/metabolism , Pleural Neoplasms/metabolism , Thoracic Neoplasms/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immune Checkpoint Inhibitors/therapeutic use , Male , Mesothelioma, Malignant/drug therapy , Mesothelioma, Malignant/pathology , Middle Aged , Pleural Neoplasms/drug therapy , Pleural Neoplasms/pathology , Prognosis , Retrospective Studies , Thoracic Neoplasms/drug therapy , Thoracic Neoplasms/pathology
6.
Sci Rep ; 11(1): 20209, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34642392

ABSTRACT

No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.


Subject(s)
Adenocarcinoma of Lung/metabolism , Carcinoma, Squamous Cell/metabolism , Lung Neoplasms/metabolism , Proteomics/methods , Aged , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Laser Capture Microdissection , Male , Middle Aged , Multivariate Analysis , Protein Interaction Maps
7.
Cancer Control ; 28: 10732748211038314, 2021.
Article in English | MEDLINE | ID: mdl-34384268

ABSTRACT

BACKGROUND: This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUVmax) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses. RESULTS: PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous invasion, positive pleural invasion, and high preoperative SUVmax (≥3). Postoperative survival analysis showed that both PD-L1 expression and preoperative SUVmax were significantly negative prognostic factors in univariate analysis for overall survival (OS) (P = 0.0123 and P < 0.0001) and relapse-free survival (RFS) (P = 0.0012 and P < 0.0001). Kaplan-Meier survival curves showed that the OS and RFS were the best in patients with negative PD-L1 expression and SUVmax < 3, intermediate in patients with positive PD-L1 expression and SUVmax < 3 and those with negative PD-L1 expression and SUVmax ≥ 3, and poor in patients with positive PD-L1 expression and SUVmax ≥ 3. CONCLUSION: Combining PD-L1 expression and preoperative FDG-PET/CT SUVmax in primary tumor might help in accurate prediction of postoperative prognosis in NSCLC patients.


Subject(s)
B7-H1 Antigen/biosynthesis , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Fluorodeoxyglucose F18/pharmacokinetics , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Aged , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/surgery , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Male , Neoplasm Invasiveness , Positron Emission Tomography Computed Tomography , Retrospective Studies , Sex Factors , Smokers/statistics & numerical data , Survival Analysis
8.
Case Rep Pulmonol ; 2020: 3268608, 2020.
Article in English | MEDLINE | ID: mdl-32082681

ABSTRACT

Pulmonary hyalinizing granuloma is a very rare benign condition. This study describes a case involving pulmonary hyalinizing granuloma in a 76-year-old man who presented with a solitary pulmonary nodule, determined through chest radiography and computed tomography, that mimicked primary lung cancer. To establish a definitive diagnosis, tumor resection was performed with histopathological analysis indicating pulmonary hyalinizing granuloma. Radiographic findings in previously reported cases showed that most patients had well-defined margins and usually bilateral, multiple lesions. In our case; however, the solitary ill-defined tumor mimicking lung cancer is an uncommon location for this rare condition.

9.
Anticancer Drugs ; 31(2): 177-182, 2020 02.
Article in English | MEDLINE | ID: mdl-31725045

ABSTRACT

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA nonsmall cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m) on days 1 and 8 followed by carboplatin area (area under the curve = 6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB-IIIA were 85.4% and 63.9%, respectively (P = 0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P = 0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II-IIIA were 83.6% and 63.6%, respectively (P = 0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P = 0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/mortality , Chemotherapy, Adjuvant/mortality , Lung Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Albumins/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Case-Control Studies , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage , Prognosis , Retrospective Studies , Survival Rate
10.
PLoS One ; 14(6): e0217105, 2019.
Article in English | MEDLINE | ID: mdl-31166966

ABSTRACT

Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis. Weighted gene co-expression network analysis (WGCNA) identified co-expressed modules and hub genes. Of 34 identified modules, six were significant and selected for protein-protein interaction (PPI) network analysis and pathway enrichment. Within the six modules, the activation of cellular processes and complexes, such as alternative mRNA splicing, translation initiation, nucleosome remodeling and deacetylase (NuRD) complex, SWItch/Sucrose Non-Fermentable (SWI/SNF) superfamily-type complex, chromatin remodeling pathway, and mRNA metabolic processes, were significant to SCLC. Modules enriched in processes, including signal recognition particle (SRP)-dependent co-translational protein targeting to membrane, nuclear-transcribed mRNA catabolic process of nonsense-mediated decay (NMD), and cellular macromolecule catabolic process, were characteristically activated in LCNEC. Novel high-degree hub genes were identified for each module. Master and upstream regulators were predicted via causal network analysis. This study provides an understanding of the molecular differences in tumorigenesis and malignancy between SCLC and LCNEC and may help identify potential therapeutic targets.


Subject(s)
Carcinoma, Large Cell/genetics , Carcinoma, Neuroendocrine/genetics , Gene Expression Profiling , Gene Regulatory Networks , Lung Neoplasms/genetics , Proteomics , Small Cell Lung Carcinoma/genetics , Aged , Carcinoma, Large Cell/metabolism , Carcinoma, Large Cell/pathology , Carcinoma, Neuroendocrine/metabolism , Carcinoma, Neuroendocrine/pathology , Female , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Protein Interaction Mapping , Small Cell Lung Carcinoma/metabolism , Small Cell Lung Carcinoma/pathology
11.
Ann Thorac Cardiovasc Surg ; 25(1): 1-9, 2019 Feb 20.
Article in English | MEDLINE | ID: mdl-30282880

ABSTRACT

PURPOSE: Knowledge regarding programmed death-ligand 1 (PD-L1) expression in lung cancer is limited. We aim to clarify PD-L1-positive expression in non-small-cell lung cancer (NSCLC), including adenocarcinoma subtypes. METHODS: In all, 90 NSCLC specimens containing various adenocarcinoma subtypes, in addition to squamous cell carcinoma and large-cell carcinoma were selected. PD-L1 was immunohistochemically stained by murine monoclonal antibody clone 22C3. RESULTS: When PD-L1-positive expression was defined by tumor proportion score (TPS) ≥1%, the positive cases were 0/11 in adenocarcinoma in situ, 0/12 in minimally invasive adenocarcinoma, 1/10 in lepidic predominant adenocarcinoma, 1/13 in papillary predominant adenocarcinoma, 8/14 in acinar predominant adenocarcinoma, 6/11 in solid predominant adenocarcinoma, 0/3 in micropapillary predominant adenocarcinoma, 0/4 in invasive mucinous adenocarcinoma, 4/9 in squamous cell carcinoma, and 2/3 in large-cell carcinoma. PD-L1 positivity was higher in males, smokers, advanced pathologic stages, positive vessel invasion, and positive lymphatic invasion. Postoperative survival analysis revealed that PD-L1-positive expression was a significantly worse prognostic factor in univariate analysis for recurrence-free survival (RFS). CONCLUSION: PD-L1-positive tumors were frequent in acinar predominant adenocarcinoma and solid predominant adenocarcinoma than other adenocarcinoma subtypes. PD-L1 expression seemed to increase according to pathologic tumor progression, suggesting a worse postoperative prognosis in NSCLC patients.


Subject(s)
Adenocarcinoma of Lung/chemistry , B7-H1 Antigen/analysis , Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/chemistry , Lung Neoplasms/chemistry , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Disease Progression , Female , Humans , Immunohistochemistry , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Pneumonectomy , Progression-Free Survival , Risk Factors , Time Factors , Treatment Outcome
12.
Thorac Cancer ; 9(1): 19-24, 2018 01.
Article in English | MEDLINE | ID: mdl-28976075

ABSTRACT

BACKGROUND: The impact of chronic obstructive pulmonary disease (COPD) severity on survival after curative resection of early-stage lung cancer (NSCLC) has not been sufficiently elucidated. METHODS: We retrospectively reviewed 250 consecutive patients who underwent lobectomy with lymph nodal dissection for pathological stage I-II NSCLC. RESULTS: Among the COPD patients, 28 were classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 21 as GOLD 2, and one as GOLD 3. The cumulative overall survival (OS) of the non-COPD, GOLD 1, and GOLD 2-3 groups at five years was 90.7%, 85.7%, and 55.3%, respectively, (P < 0.0001), while recurrence-free survival (RFS) between the groups at five years was 84.7%, 80.7%, and 72.9%, respectively. Although RFS in the GOLD 2-3 group tended to indicate a poor prognosis, there was no statistical difference between the groups (P = 0.385). In multivariate analysis, age ≥75 years, pN1, and GOLD 2-3 COPD were independent factors for a poor prognosis (P = 0.034, P = 0.010, and P = 0.030, respectively). CONCLUSIONS: Our results indicate that early stage NSCLC patients with COPD had a significantly increased risk of poorer OS and potentially an increased risk of poor RFS.


Subject(s)
Lung Neoplasms/complications , Pulmonary Disease, Chronic Obstructive/etiology , Aged , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/surgery , Male , Prognosis , Pulmonary Disease, Chronic Obstructive/mortality , Retrospective Studies , Risk Factors , Survival Analysis
13.
Clin Lung Cancer ; 19(2): 170-174, 2018 03.
Article in English | MEDLINE | ID: mdl-29150249

ABSTRACT

BACKGROUND: The reliability of the cobas EGFR assay to detect epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) as an in vitro diagnostic test was compared with 3 laboratory-developed tests (LDTs). MATERIALS AND METHODS: After screening for EGFR mutations using formalin-fixed-paraffin-embedded NSCLC tissue sections using the cobas EGFR assay, 151 samples were further tested with 3 LDTs; the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PCR) clamp, PCR invader, and Cycleave assays. The cobas EGFR assay performance was evaluated by determining the concordance rate and κ-coefficient between the assays. In samples exhibiting discrepancies in the EGFR mutation status in the 4 assays, next-generation sequencing was performed to confirm mutated sequences. RESULTS: Concordance rates and κ-coefficients between the cobas EGFR assay and the other tests were 96.0% and 0.921 for the peptide nucleic acid-locked nucleic acid PCR clamp assay, 94.0% and 0.881 for the PCR invader assay, and 96.7% and 0.934 for the Cycleave assay, respectively. Data showed very good agreement with the other assays. Precise mutated sequences or exons in the EGFR gene matched in 137 samples (90.7%). Different results were obtained in 4 samples (2.6%), owing to systemic limitations of the assay. Next-generation sequencing of 10 (6.6%) samples with discordant results exhibited a concordance rate of 60% to 80% in each assay. CONCLUSIONS: The cobas EGFR assay showed high concordance rates and κ-coefficients between the 3 compared LDTs and can be used to select patients who would benefit from EGFR-tyrosine kinase inhibitors.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , DNA Mutational Analysis/methods , Lung Neoplasms/diagnosis , Lung/physiology , Mutation/genetics , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Clinical Laboratory Techniques , Early Detection of Cancer , ErbB Receptors/genetics , Female , High-Throughput Screening Assays , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Polymerase Chain Reaction , Reproducibility of Results
14.
Thorac Cancer ; 9(1): 189-192, 2018 01.
Article in English | MEDLINE | ID: mdl-29090842

ABSTRACT

Routine clinical and pathological evaluations to determine the relationship between different lesions are often not completely conclusive. Interestingly, detailed genetic analysis of tumor samples may provide important additional information and identify second primary lung cancers. In the present study, we report cases of two synchronous lung adenocarcinomas composed of two distinct pathological subtypes with different EGFR gene mutations: a homozygous deletion in exon 19 of the papillary adenocarcinoma subtype and a point mutation of L858R in exon 21 of the tubular adenocarcinoma. The present report highlights the clinical importance of molecular cancer biomarkers to guide management decisions in cases involving multiple lung tumors.


Subject(s)
ErbB Receptors/genetics , Lung Neoplasms/genetics , Aged , Female , Humans , Lung Neoplasms/pathology , Male , Mutation
15.
J Thorac Dis ; 9(9): 3038-3044, 2017 Sep.
Article in English | MEDLINE | ID: mdl-29221277

ABSTRACT

BACKGROUND: A few investigators have suggested an association between lung cancer and pulmonary cavity. However, this clinical association and its carcinogenic correlations are not well recognized. This study aimed to clarify the clinical features and to demonstrate the associated survival outcomes after curative surgery in patients with early non-small cell lung cancer (NSCLC) adjoining pulmonary cavity formation. METHODS: We retrospectively reviewed 275 patients with pathological stage I NSCLC by re-evaluating their chest computed tomography images. Among them, we detected NSCLC adjoining pulmonary cavity formation in 12 (4.4%) patients. RESULTS: The median follow-up period for all 275 patients was 43.2 (range, 6.0-86.0) months. Of these patients, 6 (50.0%) in group CF (patients with NSCLC adjoining pulmonary cavity formation) and 19 (7.2%) in group C (the control group, n=263) died during the study period. Besides, 6 (50.0%) and 32 (12.2%) patients in groups CF and C, respectively, exhibited recurrence of the primary lung cancer. The cumulative overall survival (OS) in groups CF and C at 5 years was 37.0% and 91.7%, respectively (P<0.0001); the recurrence-free survival (RFS) in these groups at 5 years was 55.0% and 86.7%, respectively (P=0.001). Univariate analysis showed that male sex, smoking habits, non-adenocarcinoma, and presence of pulmonary cavity formation were associated with poor OS (P=0.008, P=0.001, P<0.0001, and P<0.0001, respectively). Multivariate analysis demonstrated that smoking, non-adenocarcinoma, and pulmonary cavity formation were independent prognostic factors predicting poor survival (P=0.043, P=0.004 and P<0.0001, respectively). CONCLUSIONS: Our results suggest that patients with early-stage NSCLC adjoining pulmonary cavity formation have an increased risk of poor OS and RFS after surgical resection. Further prospective, multi-institutional investigations and substantial clinical studies are warranted.

16.
Ann Thorac Cardiovasc Surg ; 23(6): 291-297, 2017 Dec 20.
Article in English | MEDLINE | ID: mdl-28966230

ABSTRACT

PURPOSE: The aim of this study was to compare the clinicopathologic prognostic factors between patients who underwent lung resection for adenocarcinoma (AD) and those with squamous cell carcinoma (SQ). METHODS: A database of patients with lung AD or SQ who underwent surgery with curative intent in our department from January 2008 to December 2014 was reviewed. Associations between various clinicopathologic factors, postsurgical recurrence-free survival (RFS), and overall survival (OS) were analyzed to find significant prognostic factors. RESULTS: A total of 537 lung cancer patients (AD, 434; SQ, 103) were included in this study. Although RFS was similar in patients with AD and SQ, OS was significantly poorer in those with SQ. Multivariate analysis in patients with AD revealed that age (≥69 vs. <69), lymphatic invasion, and histologic pleural invasion (p0 vs. p1-3) were associated with RFS, while gender and pleural invasion were associated with OS. In SQ, however, smoking, clinical stage, and pulmonary metastasis were associated with RFS in the multivariate analysis. CONCLUSION: Since significant postoperative prognostic factors are quite different between lung AD and SQ, these two histologic types should be differently analyzed in a clinical study.


Subject(s)
Adenocarcinoma of Lung/surgery , Carcinoma, Squamous Cell/surgery , Pneumonectomy , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Chi-Square Distribution , Databases, Factual , Disease Progression , Female , Humans , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local , Pneumonectomy/adverse effects , Pneumonectomy/mortality , Progression-Free Survival , Proportional Hazards Models , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young Adult
17.
Onco Targets Ther ; 10: 4135-4141, 2017.
Article in English | MEDLINE | ID: mdl-28860823

ABSTRACT

OBJECTIVE: We previously reported that the staging system and epidermal growth factor receptor (EGFR) mutation status are key factors for treatment strategy and predicting survival. However, the significance of these factors as predictors of overall survival (OS) and postoperative recurrence survival (PRS) has not been sufficiently elucidated. The objective here was to investigate EGFR mutation status and p-stage, which affect PRS and OS in patients with completely resected lung adenocarcinoma, using a different database. PATIENTS AND METHODS: We retrospectively reviewed 56 consecutive lung adenocarcinoma patients with disease recurrence in St. Marianna University Hospital between January 2010 and December 2014. RESULTS: EGFR mutants (M) were detected in 16/56 patients (29%). The patients with EGFR M had a better OS than those with EGFR wild-type (WT) status (5-year survival: 50.3% vs 43.1, P=0.133). There was no significant difference in the 3-year recurrence-free survival rate between patients with M and WT (6.3% vs 7.7%, P=0.656), and the patients with EGFR M had a significantly better 3-year PRS than those with WT (77.4% vs 51.7%, P=0.033). The 3-year PRS rate for patients with M/pathologic stage (p-stage) I-II (87.5%) was better than that for patients with M/p-stage III (60.0%), WT/p-stage I-II (52.7%), and WT/p-stage III (43.8%). There was a significant difference between patients with M/p-stage I and WT/p-stage I-II or WT/p-stage III (P=0.021 and 0.030, respectively). During the study period, of the 16 patients with mutants, 12 patients (75%) received EGFR-tyrosine kinase inhibitor (TKI) therapy and among the 40 patients with WT, no patient received EGFR-TKI therapy. Multivariate survival analysis showed that patients with EGFR-TKI therapy had a statistically significant association with favorable PRS (hazard ratio 0.271; 95% confidence interval 0.074-1.000; P=0.050). CONCLUSION: EGFR status and p-stage were found to be essential prognostic factors for estimating PRS using this database. The recurrent patients with EGFR M and EGFR-TKI therapy had a statistically significant association with favorable PRS.

18.
Anticancer Drugs ; 28(7): 795-800, 2017 08.
Article in English | MEDLINE | ID: mdl-28538017

ABSTRACT

The aim of this study was to determine the feasibility of adjuvant administration of nab-paclitaxel (nab-P) plus carboplatin and for completely resected patients with stage IB, II, and IIIA non-small-cell lung cancer (NSCLC) (FAST-nab study, UMIN000011225). Twenty-nine eligible NSCLC patients received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-P (100 mg/m) on days 1 and 8, followed by carboplatin area (area under the curve=6) on day 1. Twenty-two (75.9%) of the 29 patients enrolled completed four cycles of this regimen. The most common grade 3 or 4 adverse event experienced during the nab-P plus carboplatin was neutropenia (34.5%), followed by anemia (13.8%). No grade 3 or 4 nonhematologic adverse event was observed during this chemotherapy. The median time to disease recurrence survival was 21 (95% confidence interval: 16-26) months. The administration of modified nab-P plus carboplatin was considered an attractive alternative regimen that was safe and well tolerated as a postoperative adjuvant chemotherapy for completed resected NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Albumins/administration & dosage , Albumins/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Chemotherapy, Adjuvant , Drug Administration Schedule , Feasibility Studies , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects
20.
Onco Targets Ther ; 10: 1459-1464, 2017.
Article in English | MEDLINE | ID: mdl-28331339

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the chronological changes in epidemiological factors and surgical outcomes in patients with lung cancer who underwent surgery in a single Japanese institution. PATIENTS AND METHODS: A clinicopathological database of patients with lung cancer who underwent surgery with curative intent from January 1974 to December 2014 was reviewed. The chronological changes in various factors, including patient's age, sex, histological type, tumor size, pathological stage (p-stage), surgical method, operative time, intraoperative blood loss, 30-day mortality, and postoperative overall survival (OS), were evaluated. RESULTS: A total of 1,616 patients were included. The numbers of resected patients, females, adenocarcinomas, p-stage IA patients, and age at the time of surgery increased with time, but tumor size decreased (all P<0.0001). Concerning surgical methods, the number of sublobar resections increased, but that of pneumonectomies decreased (P<0.0001). The mean operative time, intraoperative blood loss, and the postoperative 30-day mortality rate decreased (all P<0.0001). When the patients were divided into two groups (1974-2004 and 2005-2014), the 5-year OS rates for all patients and for p-stage IA patients improved from 44% to 79% and from 73% to 89%, respectively (all P<0.0001). The best 5-year OS rate was obtained for sublobar resection (73%), followed by lobectomy (60%), combined resection (22%), and pneumonectomy (21%; P<0.0001). CONCLUSION: Changes in epidemiological factors, a trend toward less invasive surgery, and a remarkably improved postoperative OS were confirmed, which demonstrated the increasingly important role of surgery in therapeutic strategies for lung cancer.

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