Accuracy of endoscopic ultrasound-guided needle aspiration specimens for molecular diagnosis of non-small-cell lung carcinoma

BACKGROUND Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)are highly sensitive for diagnosing and staging lung cancer.In recent years,targeted therapy has shown great significance in the treatment of non-small cell lung carcinoma(NSCLC).Using these minimally invasive techniques to obtain specimens for molecular testing will provide patients with a more convenient diagnostic approach.AIM To evaluate the feasibility and accuracy of tissue samples obtained using EUSFNA and EBUS-TBNA for molecular diagnosis of NSCLC.METHODS A total of 83 patients with NSCLC underwent molecular testing using tissues obtained from EUS-FNA or EBUS-TBNA at the Tianjin Medical University Cancer Hospital from January 2017 to June 2019.All enrolled patients underwent chest computed tomography or positron emission tomography/computed tomography prior to puncture.We detected abnormal expression of EGFR,KRAS,MET,HER2,ROS1 and anaplastic lymphoma kinase protein.Two patients failed to complete molecular testing due to insufficient tumor tissue.The clinical features,puncture records,molecular testing results and targeted treatment in the remaining 81 patients were summarized.RESULTS In a total of 99 tissue samples obtained from 83 patients,molecular testing was successfully completed in 93 samples with a sample adequacy ratio of 93.9%(93/99).Biopsy samples from two patients failed to provide test results due to insufficient tumor tissue.In the remaining 81 patients,62 cases(76.5%)were found to have adenocarcinoma,11 cases(13.6%)had squamous cell carcinoma,3 cases(3.7%)had adenosquamous carcinoma and 5 cases(6.2%)had NSCLC-not otherwise specified.The results of molecular testing showed EGFR mutations in 21 cases(25.9%),KRAS mutations in 9 cases(11.1%),ROS-1 rearrangement in 1 case(1.2%)and anaplastic lymphoma kinase-positive in 5 cases(6.2%).Twentyfour patients with positive results received targeted therapy.The total effectiveness rate of targeted therapy was 66.7%(16/24),and the disease control rate was 83.3%(20/24).CONCLUSION Tissue samples obtained by EUS-FNA or EBUS-TBNA are feasible for the molecular diagnosis of NSCLC and can provide reliable evidence for clinical diagnosis and treatment.

Glabridin and Anti-Non-Muscle Myosin IIA Therapy Disrupts Non-Small Cell Lung Carcinoma Motility

Lung cancer is the leading cause of cancer related death in the United States killing over 130,000 people each year. While a combination of chemo and radiation therapy may be effective, surgery is still required for many patients. Without surgery, the disease may progress and lead to metastases. We sought to determine if treatment with anti-non-muscle myosin IIA antibody would inhibit movement of the cells in the presence and absence of glabridin (an isoflavonoid compound shown to inhibit cell migration by inhibiting myosin). We compared inhibition by glabridin to that of an anti-non-muscle myosin IIA antibody and a combination therapy of both at 12 and 24 hours post wound creation. Cells that took up the anti-non-muscle myosin IIA antibody were greatly inhibited in motility and exhibited no significant change in wound healing. Glabridin treatment resulted in a dramatic increase in wound size within 12 hours and regeneration within 24 hours. The greatest decrease in motility was observed in cells treated with the combination of both glabridin and anti-non-muscle myosin IIA antibody. By 24 hrs, cell migration had halted due to death of the cells resulting from this combination. Further testing needs to be done to determine a safe mode of delivery of the combination therapy to ensure only local distribution. Controlled release drug delivery depot systems have been used as a means to provide local release of drugs intra-tumorally or adjacent to the cancerous tissue after surgical resection and have great potential.

EGFR mutation identifies distant squamous cell carcinoma as metastasis from lung adenocarcinoma

Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carcinoma in her femur; both tumors had an identical epidermal growth factor receptor mutation, G719 S. This indicated that both tumors had a common origin, despite their histologic dissimilarity. The tumor in the femur was thus identified genetically as a lung cancer metastasis. This case suggests that genetic analysis can determine whether a distant lesion is a lung cancermetastasis, particularly when the histology differs from that of the primary lesion.

Gli1 promotes epithelial-mesenchymal transition and metastasis of non-small cell lung carcinoma by regulating snail transcriptional activity and stability

Metastasis is crucial for the mortality of non-small cell lung carcinoma(NSCLC) patients.The epithelial-mesenchymal transition(EMT) plays a critical role in regulating tumor metastasis.Glioma-associated oncogene 1(Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein,we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Adenocarcinoma transformed into squamous cell carcinoma in non-small cell lung cancer

Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcinoma(ADC),squamous cell carcinoma(SCC),adeno-squamous cell carcinoma(AD-SCC)and large cell carcinoma(LCC).

Non-Small Cell Lung Cancer: Treatment, Diagnosis, and Life after Treatment

Lung cancer is becoming the most common cancer globally. In China, Lung cancer has become prevalent among preceding compared to present smokers. There are many treatments for lung cancer globally like Chemotherapy, Radiotherapy, Surgery, and Targeted therapy [1] [2]. Generally, lung cancer starts in the lungs. The spongy lungs in the chest inhale oxygen and exhale carbon dioxide. Those who smoke regularly have the highest risk of lung cancer than nonsmokers. This risk increases with an increase in length, time, and the number of cigarettes smoked. Immediate treatment will help in reducing the severity of cancer. The complications of lung cancer include shortness of breath, coughing up blood, pain, and fluid in the chest. Therefore, the primary step in preventing lung cancer is quitting smoking [3].

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

Proportion and clinical features of never-smokers with non-small cell lung cancer

Background: The proportion of never?smokers with non?small cell lung cancer(NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never?smokers with NSCLC in a large single institution.Methods: We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014.Results: Of the 1860 NSCLC patients, 707(38.0%) were never?smokers. The proportions of women(83.7% vs. 5.6%) and adenocarcinoma(89.8% vs. 44.9%) were higher among never?smokers than among ever?smokers. Significantly more never?smokers were diagnosed at a younger median age(65 vs. 68 years, P < 0.001) and earlier stage(stage I–II, 44.5% vs. 38.9%, P < 0.001) a= 0.015) compared with ever?smokers. Epidermal growth factor receptor mutations(57.8% vs. 24.4%, Pnd anaplastic lymphoma kinase rearrangements(7.8% vs. 2.8%, P < 0.001) were more common in never?smokers, whereas Kirsten rat sarcoma viral oncogene homolog mutations(5.8% vs. 9.6%, P ntly encountered in never?smokers than in ever?smokers. Never?smokers showed longer su= 0.021) were less frequervival after adjust?ing for the favorable effects of younger age, female sex, adenocarcinoma histology, better performance status, early stage disease, being asymptomatic at diagnosis, received antitumor treatment, and the presence of driver mutations(hazard ratio, 0.624; 95% confidence interval, 0.460–0.848; P = 0.003).Conclusions: More than one?third of the Korean patients with NSCLC were never?smokers. NSCLC in never?smokers had different clinical characteristics and major driver mutations and resulted in longer overall survival compared with NSCLC in ever?smokers.

Current treatment landscape for oligometastatic non-small cell lung cancer

The management of patients with advanced non-small cell lung carcinoma(NSCLC)has undergone major changes in recent years.On the one hand,improved sensitivity of diagnostic tests,both radiological and endoscopic,has altered the way patients are staged.On the other hand,the arrival of new drugs with antitumoral activity,such as targeted therapies or immunotherapy,has changed the prognosis of patients,improving disease control and prolonging survival.Finally,the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body.All of these advances have impacted the treatment of patients with advanced lung cancer,especially in a subgroup of these patients in which all of these treatment modalities converge.This poses a challenge for physicians who must decide upon the best treatment strategy for each patient,without solid evidence for one optimal mode of treatment in this patient population.The aim of this article is to review,from a practical and multidisciplinary perspective,published evidence on the management of oligometastatic NSCLC patients.We evaluate the different alternatives for radical ablative treatments,the role of primary tumor resection or radiation,the impact of systemic treatments,and the therapeutic sequence.In short,the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.

Application of non-small cell lung cancer pleural effusion cell blocks in molecular pathological detection

Objective: The tumor tissues used in molecular pathological detection were usually obtained by surgery, which would cause trauma and may not be suitable for the terminal cancer patients. This paper evaluated the value of the non-small cell lung cancer(NSCLC) pleural effusion cell blocks as tumor tissues replacement materials in the application of molecular pathological detection. Methods: Tumor cells were made into cell blocks through stratified centrifugal from 30 NSCLC patients with the pleural effusion. The immunohistochemistry, fluorescence in situ hybridization(FISH) and gene sequencing methods were employed in our experiments. Results: The tumor cells of cell block section were rich and could keep part of histological structure. Immunohistochemistry staining could assist diagnosis and tumor parting. Epidermal growth factor receptor(EGFR) FISH-positive was found in 33.33% of the group, high polysomy in 6 cases, amplification in 4 cases. EGFR gene mutations were found in 8 cases of 30 samples, with an incidence of 26.67%, 6 cases were detected in the exon 19, and 2 cases were detected in the exon 21. Conclusion: The NSCLC pleural effusion cell blocks are useful for the diagnosis and determining the primary source of tumor, instructed targeted therapy.

Therapeutic guidance of tumor mutation burden on immune checkpoint inhibitors in advanced non-small cell lung cancer:a systematic review and comprehensive meta-analysis

Background:Tumor mutation burden(TMB)remains a promising but ambiguous predictive biomarker for the efficacy of immune checkpoint inhibitors(ICIs).We investigated the predictive value of TMB in patients with advanced non-small cell lung cancer(NSCLC)treated by ICI-containing therapies under strictly matched clinical settings.Methods:PubMed,Embase,Cochrane Central,ClinicalTrials.gov,and bioRxiv databases were searched till October 16,2021.All randomized controlled trials(RCTs)that compared patients with high TMB(TMB-H)and low TMB(TMB-L)and provided hazard ratio(HR)and corresponding 95%confidence interval(CI)in advanced NSCLC patients receiving ICIs were included,and mirror-based meta-analysis was performed(Part1).Bayesian network meta-analysis was conducted to investigate the efficacy of distinct first-line regimens in TMB-H and TMB-L groups(Part2).Public cohorts were used for validation and further exploration(Part3).Results:Twelve RCTs(n=5527)and 5 public cohorts(n=573)were included.In Part1,TMB-H patients generally exhibited a more significant progression-free survival(PFS)benefit from ICI-containing therapies compared to TMB-L patients(HR=0.58,95%CI:0.49-0.67,P<0.0001).In Part2,anti-PD-1 plus chemotherapy ranked best for PFS in both TMB-H and TMB-L groups.Anti-PD-L1 plus anti-CTLA-4 therapies indicated better PFS and overall survival(OS)benefit than single ICI and chemotherapy in the TMB-H group,but ranked worst in the TMB-L group.Finally,TMB was validated to be an independent predictive biomarker from programmed cell death-ligand 1(PD-L1)expression in Part3,which could further distinguish beneficiaries of ICI-containing therapies with PD-L1<50%.Conclusion:TMB-H could be a predictive biomarker independent of PD-L1 expression to identify beneficiaries of ICI-containing therapy in advanced NSCLC patients.

CLINICAL EFFICACY OF VINORELBINE PLUS CISPLATIN IN ADVANCED NON-SMALL CELL LUNG CANCER

A clinical study of the efficacy of vinorelbine plus cisplatin regimen in the management of advanced NSCLC was performed in 35 patients. Five of the 35 patients failed to finish one cycle of chemotherapy with this regimen because of severe and intractable leukopenia or rapid progress of the disease. Tumor response and toxicity were evaluated in the remaining 30 cases. Results showed that, with this regimen, the objective response rate (CR+PR) was 46.7%. The most common toxicity was leukopenia; other side effects included alopecia, gastrointestinal reactions, slight and transient renal and hepatic impairment and peripheral neuropathy. It suggested that vinorelbine plus cisplatin is a safe and effective regimen in the management of advanced NSCLC.

Clinical pathology of nodal micrometasteses in non-small cell lung cancer

Objective： To explore whether the conventional pathologic stages of some non-small cell lung cancer （NSCLC） patients were underestimated. Methods： 195 lymph node samples were taken from 25 NSCLC patients during the operations. Firstly, each resulting tissue block was processed for routine paraffin embedding. Then the 6- 10 serial sections were chosen, each 5/am thick, from every paraffin block of the lymph node. Finally, the first and the second last sections of each lymph node were stained by hematoxylin eosin （HE）, and the other serial sections were used for the immunohistochemical （IHC） staining examination with the monoclonal antibody against cyokeratin 19. Results： With HE staining, 30 of the 195 regional lymph nodes revealed dominant nodal metastases, and none showed micrometastases. IHC staining was performed on 135 lymph nodes that were identified as free of metastases by HE staining, 31 showed micrometastases; none showed gross nodal metastases. There was a significant difference between HE staining staging and IHC staining staging （P〈0.05）. Conclusion： Conventional HE staining can accurately detect gross nodal metastases in the lymph nodes of NSCLC patients, but is unfit for detecting lymph nodal micrometastases. IHC staining analysis can significantly facilitate the detection of occult micrometastatic tumor cells in lymph nodes, and its assessment of nodal micrometastases can provide a refinement of TNM stage for NSCLC patients. Our results provide a rationale for extensive lymph nodes sampling

Intraoperative photodynamic therapy for tracheal mass in non-small cell lung cancer:A case report

BACKGROUND Tracheal neoplasms represent less than 0.1%of all malignancies and have no established treatment guidelines.Surgical resection with reconstruction is the primary treatment.This study demonstrates successful treatment of concurrent lung and tracheal tumors using surgical excision and intraoperative photodynamic therapy(PDT),highlighting the effectiveness and safety of this approach.CASE SUMMARY A 74-year-old male with a history of smoking and chronic obstructive pulmonary disease was diagnosed with tracheal squamous cell carcinoma and right lower lobe adenocarcinoma.A multidisciplinary team created a treatment plan involving tumor resection and PDT.The tracheal tumor was removed through a tracheal incision and this was followed by intraluminal PDT.The trachea was repaired and a right lower lobectomy was performed.The patient received a second PDT treatment postoperatively and was discharged 10 d after the tracheal surgery,without complications.He then underwent platinum-based chemotherapy for lymphovascular invasion of lung cancer.Three-month postoperative bronchoscopy revealed normal tracheal mucosa with a scar at the resection site and no evidence of tumor recurrence in the trachea or lung.CONCLUSION Our case of concurrent tracheal and lung cancers was successfully treated with surgical excision and intraoperative PDT which proved safe and effective in this patient.

Favorable response of primary pulmonary lymphoepithelioma-like carcinoma to sintilimab combined with chemotherapy: A case report

BACKGROUND There is no established treatment for primary pulmonary lymphoepithelioma-like carcinoma(LELC)until now.CASE SUMMARY In this study,the patient responded well to sintilimab combined with paclitaxel and carboplatin,showing no obvious side effects.Meantime,the values of carbohydrate antigen 15-3(CA15-3)and carbohydrate antigen 72-4(CA72-4)gradually returned to normal.CONCLUSION Immunotherapy combined with chemotherapy in advanced-stage LELC may be more effective than immunotherapy or chemotherapy alone.CA15-3 and CA72-4 are biomarkers for evaluating therapeutic effects for LELC.

Initial outcome of induction chemotherapy followed by radiotherapy and concurrent weekly paclitaxel for stage Ⅲ non-small cell lung cancer

Objective： The aim of our study was to evaluate the toxicity and efficacy of induction chemotherapy （ICT） followed by three-dimensional conformal radiotherapy （3D CRT） and concurrent weekly paclitaxel on unresectable non-small cell lung cancer （NSCLC）. Methods： Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin （AUC = 5-6, dl） combined with paclitaxel （175 mg/m〈 dl）, then followed by weekly paclitaxel （40 mg/m2） and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 〈 31% and spinal cord dose 〈 50 Gy. Results： Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild （16/31）： all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious （29/31, grade 3 in 21）. Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grades 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grades 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. Conclusion： The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.

Analysis of prognostic factors for overall survival in patients with advanced non-small cell lung cancer treated with second line chemotherapy

Aim: The aim of this study was to investigate prognostic factors for survival in patients with advanced NSCLC who receiving second-line chemotherapy. Methods: We retrospectively reviewed data of 116 patients with NSCLC receiving second-line treatments from October 2010 to December 2012 in Clinic for Lung Diseases of Clinical center Nis, Department for Pulmonary Oncology. Thirteen potential prognostic factors were chosen for analysis. Univariate analysis was conducted to identify prognostic factors associated with progression free survival and overall survival. Multivariate analysis included the prognostic significance factors in univariate analysis. Results: The univariate analysis for progression free survival (PFS) and overall survival (OS) was identified to have prognostic significance: performance status, smoking, weight loss, comorbidity, number of meta localization, first-line chemotherapy regimen and response to first-line chemotherapy. Nevertheless, multivariate Cox prortional hazard regression analysis showed that performance status (PFS: p = 0.000, OS: p = 0.000) weight loss ≥ 5% (PFS: p = 0.000, OS: p = 0.002), comorbidity (PFS: p = 0.001, OS: p = 0.012) and four places of meta localization (PFS: p = 0.021, OS: p = 0.021) were considered independent prognostic factors for both, progression free survival and overall survival. Conclusion: Performance status, weight loss ≥ 5%, comorbidity and higher number of meta localization were identified as prognostic factors for survival in advanced NSCLC patients receiving second-line chemotherapy treatment. These findings may help pretreatment prediction of survival and may facilitate in the future integration new agents into second-line treatment.

Serum miR-339-3p as a potential diagnostic marker for non-small cell lung cancer

Objective:MicroRNA(miRNA),a short noncoding RNA,is claimed to be a potential blood-based biomarker.We aimed to identify and evaluate miRNAs as diagnostic biomarkers for non-small cell lung cancer(NSCLC).Methods:Profiles of 745 miRNAs were screened in the serum of 8 patients with NSCLC and 8 age-and sex-matched controls using TaqMan low-density arrays(TLDAs)and validated in 25 patients with NSCLC and 30 with other lung diseases(OLs)as well as in 19 healthy persons(HPs).The diagnostic performance of the candidate miRNAs was assessed in 117 cases of NSCLC and 113 OLs using quantitative real-time polymerase chain reaction(qRT-PCR).Differences in miRNA expression between patients with NSCLC and controls were assessed using the Mann–Whitney U test.The area under receiver operating characteristic(ROC)curve(AUC)was obtained based on the logistic regression model.Results:Ten miRNAs were found to be differentialy expressed between patients with NSCLC and controls,including miR-769,miR-339-3p,miR-339-5p,miR-519a,miR-1238,miR-99a#,miR-134,miR-604,miR-539,and miR-342.The expression of miR-339-3p was significantly higher in patients with NSCLC than in those with OLs(P<0.001)and HPs(P=0.020).ROC analysis revealed an miR-339-3p expression AUC of 0.616[95%confidence interval(CI):0.561–0.702].The diagnostic prediction was increased(AUC=0.706,95%CI:0.649–0.779)in the model combining miR-339-3p expression and other known risk factors(i.e.,age,smoking status,and drinking status).Conclusions:MiR-339-3p was significantly upregulated in patients with NSCLC compared with participants without cancer,suggesting a diagnostic prediction value for high-risk individuals.Therefore,miR-339-3p expression could be a potential blood-based biomarker for NSCLC.

Application of artificial intelligence in clinical non-small cell lung cancer

Lung cancer is the most common cause of cancer death in the world.Early diagnosis,screening and precise individualized treatment can significantly reduce the death rate of lung cancer.Artificial intelligence(AI)has been shown to be able to help clinicians make more accurate judgments and decisions in many ways.It has been involved in the screening of lung cancer,the judgment of benign and malignant degree of pulmonary nodules,the classification of histological cancer,the differentiation of histological subtypes,the identification of genomics,the judgment of the effectiveness of treatment and even the prognosis.AI has shown that it can be an excellent assistant for clinicians.This paper reviews the application of AI in the field of non-small cell lung cancer and describes the relevant progress.Although most of the studies to evaluate the clinical application of AI in non-small cell lung cancer have not been repeatable and generalizable,the research results highlight the efforts to promote the clinical application of AI technology and influence the future treatment direction.

Lung squamous cell carcinoma combined with tuberculous pleurisy

A58-year old male patient was admitted to our .hospital with repeated coughing, expectoration withblood in the sputum for more than 10 months, bilateral wrists and ankles with pain and afternoon low fever, chest tightness and shortness of breath in the latest one month. The patient had a history of joint pain for more than 3 years without special treatment. He had a smoking history for more than 30 years with 10 cigarettes a day. He had no family tumor history. Physical examination： T 38.5℃, P 100/min, R 22/min, blood pressure （BP） 107/77 mmHg; the double upper fingers visible clubbing, bilateral supraclavicular lymph node not feelable, left inferior pulmonary respiratory sounds disappeared, and wet and dry sounds not heard.