The Diagnostic Value Of Ultrasound Bronchoscopy For Mediastinal Enlarged Lymph Nodes And The Detection Value Of PD-L1

Part1:VALUE OF ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSBRONCHIAL NEEDLE ASPIRATION IN MEDIASTINAL LYMPHADENOPAHTY AND INVESTIGATION OF FALSE NEGATIVEObjective:AThe incidence of lung cancer continues to rise on a global scale.The incidence and mortality of lung cancer in Chinese men account for the first place in all malignant tumors,and the number continues to grow[1-2],but the majority of patients diagnosed at the time of lymph nodes or has occurred elsewhere,resulting in unsatisfactory treatment and survival of lung cancer patients.The prognosis and treatment are dependent on clinical staging.The common route of lymph node metastasis of lung cancer is mediastinum and hilar lymph nodes.Diagnostic staging or post-treatment staging depends on accurate mediastinal lymph nodes.Endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)is a new technique for the diagnosis and treatment of mediastinal diseases.the technology is the combination of ultrasound and bronchoscope technology,can be real-time display blood vessels,lymph nodes,the location of the lesions and relationships,and to locate the puncture.In recent years,ebus-tbna has been found to be of high application value in the diagnosis of mediastinal benign and malignant lymph nodes and mediastinal lymph node staging of lung cancer,and is an effective method for mediastinal lymph node examination recommended by international guidelines.This study retrospectively analyzed the clinical data of 389 patients with mediastinal lymph nodes with EBUS-TBNA and explored the causes of false negatives in EBUS-TBNA diagnosis.To improve the positive rate of puncture and guide clinical practice.Methods:Retrospectively analyzed the patient data of the endoscopy department of the Shandong Cancer Hospital from October 2009 to October 2015,including inpatients and outpatients.Imaging showed mediastinal lymphadenopathy,but no pathological diagnosis was obtained by bronchoscopy and other examinations,and EBUS-TBNA examination test is required.The histopathological and/or cytological results of the patients were statistically analyzed to discuss the accuracy,sensitivity,specificity,cytology and histopathological diagnosis of lymph node positive rate and other indicators,and to analyze the reasons for the false negative of pathology and/or cytology.Results:Among the 389 patients,362 were positive for puncture and 27 were negative for puncture.The sensitivity was 92.9%,the specificity was 100%,positive predictive value was 100%,negative predictive value was 25%.The positive rate of EBUS-TBNA was related to lymph node diameter(p=0.021).The highest positive rate of lymph node puncture was subarachnoid lymph node(97.7%),followed by paratracheal lymph node(91.2%),the difference was statistically significant(P=0.006).The positive rate of EBUS-TBNA puncture was not related to pathological type(P=0.932).The positive rates of lymph node diagnosis in cytology and pathology were 88.7%and 92.5%,respectively,with no statistically significant difference(P=0.065).There was no significant difference in the diagnostic accuracy of the lesions between the puncture needle types(21G and 22G,respectively)(P=0.142).During the examination,patients were well tolerated and no serious complications occurred in all patients.Conclusion:EBUS-TBNA is a minimally invasive,local anesthesia,safe and reproducible feature in the accurate diagnosis and staging of chest tumors.It is a practical technique for the diagnosis and evaluation of tumor staging in mediastinal lymph nodes with high clinical application value.In actual work,with the increase of puncture cases,the accumulation of operational experience,proficiency and technical improvement,the proportion and quality of the obtained specimens will increase,the proportion of the biopsy pathology and cytology have obviously improved,Strengthening cooperation and communication with pathologists and cytologists can further reduce the occurrence of false negatives.PART ?:STUDY ON THE EFFECTIVENESS OF LUNG CANCER SPECIMENS BASED ON EBUS-TBNA AND THE EXPRESSION OF PD-L1 IN NSCLC SPECIMENSObjective:EGFR mutation is the first identified lung cancer driver gene and one of the most commonly mutated oncogenes in NSCLC patients.As a key regulatory molecule in cell signaling pathway,EGFR mutation promotes tumor cell proliferation,invasion and metastasis.At present,the EGFR signaling pathway has become the most important target in the field of lung cancer targeted therapy.However,only a portion of NSCLC patients are sensitive to EGFR-TKIs,and tumors that are initially sensitive to EGFR can become resistant to TKIs by acquiring secondary point mutations(T790M)of EGFR or changes in other genes,and targeted therapy for clinical observation of TKIs cannot significantly prolong OS.For lung cancer patients without genetic mutations,cytotoxic chemotherapy with moderate efficacy and significant toxicity is still the main treatment method for most NSCLC patients,but its efficacy is limited and toxic side effects are large,resulting in a poor prognosis of NSCLC patients at present,with the 5-year overall survival rate(OS)of 15%of all stages.With the advent of the era of immunotherapy for cancer,studies on the PD-1/PD-L1 pathway have increased.PD-1 after activation and its interaction between ligands PD-L1 inhibits the initial activation of T cells,block the effects of the activation of T cell proliferation,and inhibition effect of T cell and function(including the production of cytokines and cell toxicity),lead to lower T cell response,thereby inhibit the expression of T cell mediated by PD-1 the effective identification,kill tumor cells,the tumor immune escape,tumor cells and then effectively to form a proper tumor microenvironment and continue to proliferate.At the same time,activation of PD-1/PD-L1 pathway can also change T cell differentiation,thus significantly inhibiting the immune effect of T cells.Many tumor cells,including lung cancer cells,use PD-L1 as a mechanism to inhibit T cell responses.On the other hand,immunocheckpoint inhibitors can restore T cell response,reduce specific T cell apoptosis,suppress tumor immune response,and prevent NSCLC tumor escape.Tumor immunotherapy can recognize and kill tumor cells by stimulating and enhancing the immune function of the body or regulating the immune state.Therefore,blocking the PD-1/PD-L1 pathway,namely the immune checkpoint inhibitor of PD-1/PD-L1,can activate and up-regulate T cells,activate endogenous anti-tumor immune response,and thus be used for tumor therapy.At present,the correlation between PD-1,PD-L1 and EGFR mutations in NSCLC patients is still in the initial stage.This paper explores the feasibility and effectiveness of PD-L1 in small puncture specimens and cytological specimens of patients with NSCLC diagnosed by EBUS-TBNA,and compared the accuracy of the two results with surgical resection specimens.Observe the relationship between PD-1/PD-L1 pathway and EGFR pathway,and explore their possible mechanisms of action,and look forward to future research priorities in this field.Methods:Retrospectively analyzed from September 2016 to December 2018,the imaging findings in the Shandong Cancer Hospital indicates mediastinal lymphadenopathy,but the examination such as bronchoscopy and other examinations did not obtain pathological diagnosis,EBUS-TBNA examination was required.Patients who obtained small tissue specimens and/or cytology specimens by EBUS-TBNA examination,obtained histopathological specimens after thoracoscopic or thoracotomy,all of which were subjected toPD-L1 immunohistochemistry,using amplification-blocking mutation systems.(Amplification Refractory Mutation System,ARMS)and fluorescent PCR technology for mutation detection of EGFR gene in sample DNA.To evaluate the EGFR mutations in all patients,and the value of PD-L1 in lung cancer patients was preliminarily discussed by analyzing its relationship with clinicopathological features and EGFR gene status,so as to provide more reliable scientific basis for clinical diagnosis and treatment evaluation.Results:A total of 159 patients with small tissue and/or cytology were selected,including 51 patients with stage ?,59 patients with stage III,49 patients with stage ?,and 96 cases with pathological type of adenocarcinoma.43 cases of squamous cell carcinoma and 20 cases of other pathological types.Specimens included 122 small tissue specimens and 134 cytological specimens obtained from EBUS-TBNA.68 of the 159 patients underwent thoracoscopic or thoracotomy and 68 cases of histological specimens,the mutation rate of EGFR gene was 59.7%,and the main mutation types of patients included 19del and 21L858R.PD-L1 expression was associated with gender,age,smoking,pathological type and EGFR mutation in NSCLC patients(P<0.05),but not TNM staging(P>0.05).The results of the cytology specimens and small tissue strips obtained by EBUS-TBNA examination were comparable to those of the surgically resected specimen PD-L1,demonstrating that EBUS-TBNA specimens can be used for PD-1/PD-L1 detection in NSCLC patients.Conclusion:It is feasible to quantify PD-L1 expression in cytology and small tissue samples obtained from EBUS-TBNA,providing an important detection method for patients with advanced and/or inoperable patients.In the clinical diagnosis work,patients with NSCLC should also pay attention to the detection of PD-LI while analyzing gene mutations and further analyze anti-PD-1/PD-L1 immunity,provide more effective experimental data for guiding clinical drugs,further analysis of PD-1/PD-L1 immune treatment mechanism,function and with genes such as EGFR signaling pathway connection,will make the joint application of immunotherapy and targeted therapy,more reasonable guide the treatment of lung cancer.