1.Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis.
Fei SU ; Ke ZHENG ; Yiyun FU ; Qian WU ; Yuan TANG ; Weiya WANG ; Lili JIANG
Chinese Journal of Lung Cancer 2018;21(5):389-396
BACKGROUND:
Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy.
METHODS:
ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed.
RESULTS:
The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS).
CONCLUSIONS
For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.
Adenocarcinoma
;
blood
;
drug therapy
;
genetics
;
mortality
;
Adenocarcinoma of Lung
;
Adult
;
Aged
;
Aged, 80 and over
;
Cell-Free Nucleic Acids
;
blood
;
ErbB Receptors
;
genetics
;
Female
;
Humans
;
Lung Neoplasms
;
blood
;
drug therapy
;
genetics
;
mortality
;
Male
;
Middle Aged
;
Molecular Targeted Therapy
;
Mutation, Missense
;
Prognosis
2.Health Effects of Particulate Matter.
Korean Journal of Medicine 2016;91(2):106-113
Sand dust is a source of particulate matter (PM) in Korea. Recently, an attention has been focused on the health effects of PM and fine PM. Here we examine the possible mechanisms of PM disposition and review the literature on the health effects of PM. PM can enter and accumulate in the respiratory tract via impaction, gravitational settling, diffusion, and electrostatic attractions. PM may cause oxidative stress, inflammation, direct penetration, and increased blood viscosity. This literature review revealed that PM exposure is associated with several health risks, such as mortality and respiratory and cardiovascular diseases. Furthermore, PM exposure may be linked to lung cancer. Thus, a comprehensive approach is needed to manage PM and reduce its environmental exposure and related health effects.
Air Pollutants
;
Blood Viscosity
;
Cardiovascular Diseases
;
Diffusion
;
Dust
;
Environmental Exposure
;
Inflammation
;
Korea
;
Lung Neoplasms
;
Mortality
;
Oxidative Stress
;
Particulate Matter*
;
Respiratory System
;
Silicon Dioxide
3.Early Extracorporeal Membrane Oxygenation for Massive Aspiration during Anesthesia Induction.
Namo KIM ; Kwan Hyung KIM ; Jeong Min KIM ; Su Youn CHOI ; Sungwon NA
Korean Journal of Critical Care Medicine 2015;30(2):109-114
Although the incidence is not high in the general surgical population, pulmonary aspiration of gastric contents can result in serious long-term morbidity and mortality. We report a case of early use of extracorporeal membrane oxygenation (ECMO) to correct severe hypoxemia refractory to conventional mechanical ventilation in a patient with massive aspiration of gastric contents immediately followed by acute lung injury during general anesthesia induction. A 64-year-old woman diagnosed with stomach cancer was scheduled for elective diagnostic laparoscopy. Although there was no sign of gastrointestinal tract obstruction and midnight Nil per Os (NPO) was performed before the operation, pulmonary aspiration occurred during the induction of anesthesia. Despite the endotracheal intubation with mechanical ventilation, severe hypoxemia with hypercapnea persisted. Medical team agreed with applying veno-venous (VV) ECMO, and her blood gas analysis results became stable. ECMO was weaned successfully 9 days after the first aspiration event had occurred. Based on this case, early application of extracorporeal life support can have survival benefits.
Acute Lung Injury
;
Anesthesia*
;
Anesthesia, General
;
Anoxia
;
Blood Gas Analysis
;
Extracorporeal Membrane Oxygenation*
;
Female
;
Gastrointestinal Tract
;
Humans
;
Incidence
;
Intubation, Intratracheal
;
Laparoscopy
;
Middle Aged
;
Mortality
;
Pneumonia, Aspiration
;
Respiration, Artificial
;
Stomach Neoplasms
4.Early Extracorporeal Membrane Oxygenation for Massive Aspiration during Anesthesia Induction
Namo KIM ; Kwan Hyung KIM ; Jeong Min KIM ; Su Youn CHOI ; Sungwon NA
The Korean Journal of Critical Care Medicine 2015;30(2):109-114
Although the incidence is not high in the general surgical population, pulmonary aspiration of gastric contents can result in serious long-term morbidity and mortality. We report a case of early use of extracorporeal membrane oxygenation (ECMO) to correct severe hypoxemia refractory to conventional mechanical ventilation in a patient with massive aspiration of gastric contents immediately followed by acute lung injury during general anesthesia induction. A 64-year-old woman diagnosed with stomach cancer was scheduled for elective diagnostic laparoscopy. Although there was no sign of gastrointestinal tract obstruction and midnight Nil per Os (NPO) was performed before the operation, pulmonary aspiration occurred during the induction of anesthesia. Despite the endotracheal intubation with mechanical ventilation, severe hypoxemia with hypercapnea persisted. Medical team agreed with applying veno-venous (VV) ECMO, and her blood gas analysis results became stable. ECMO was weaned successfully 9 days after the first aspiration event had occurred. Based on this case, early application of extracorporeal life support can have survival benefits.
Acute Lung Injury
;
Anesthesia
;
Anesthesia, General
;
Anoxia
;
Blood Gas Analysis
;
Extracorporeal Membrane Oxygenation
;
Female
;
Gastrointestinal Tract
;
Humans
;
Incidence
;
Intubation, Intratracheal
;
Laparoscopy
;
Middle Aged
;
Mortality
;
Pneumonia, Aspiration
;
Respiration, Artificial
;
Stomach Neoplasms
5.Prognostic Significance of Initial Platelet Counts and Fibrinogen Level in Advanced Non-Small Cell Lung Cancer.
Kyung Hee KIM ; Tae Yun PARK ; Ji Yeun LEE ; Sang Min LEE ; Jae Joon YIM ; Chul Gyu YOO ; Young Whan KIM ; Sung Koo HAN ; Seok Chul YANG
Journal of Korean Medical Science 2014;29(4):507-511
Thrombocytosis and coagulation systems activation are commonly associated with disease progression and are suggested poor prognostic factors in patients with malignancies. This study aimed to investigate the prevalence and prognostic significance of thrombocytosis and elevated fibrinogen levels in patients with advanced non-small cell lung cancer (NSCLC). Initial platelet counts and fibrinogen levels were reviewed in 854 patients with histologically proven NSCLC. Thrombocytosis was defined as platelet counts > 450 x 10(9)/L. A serum fibrinogen level > 4.5 g/L was considered high. At the time of diagnosis, initial platelet counts and serum fibrinogen levels were evaluated before treatment. Clinicopathologic data including histological type, tumor, node, metastasis (TNM) stage, performance status, treatment method, and survival time were evaluated. Initial thrombocytosis was found in 6.9% of patients, and elevated fibrinogen levels were found in 55.1% of patients. Patients with thrombocytosis had a significantly poorer prognosis than patients with normal platelet counts (P < 0.001). In multivariate survival analysis, thrombocytosis was an independent prognostic factor (P < 0.001). An elevated serum fibrinogen level was associated with poor prognosis (P < 0.001). In conclusion, initial thrombocytosis and a high fibrinogen level are independent factors for predicting poor prognosis in patients with advanced NSCLC.
Aged
;
Blood Platelets/*cytology
;
Carcinoma, Non-Small-Cell Lung/*diagnosis/mortality/pathology
;
Female
;
Fibrinogen/*analysis
;
Humans
;
Lung Neoplasms/*diagnosis/mortality/pathology
;
Male
;
Middle Aged
;
Neoplasm Staging
;
Platelet Count
;
Prognosis
;
Retrospective Studies
;
Survival Rate
;
Thrombocytosis/complications/diagnosis
6.Elevated Serum C-Reactive Protein as a Prognostic Marker in Small Cell Lung Cancer.
Soojung HONG ; Young Ae KANG ; Byoung Chul CHO ; Dae Joon KIM
Yonsei Medical Journal 2012;53(1):111-117
PURPOSE: Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC). MATERIALS AND METHODS: The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Cox's proportional hazards model. RESULTS: The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRp group was significantly longer than with the high CRp group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRp level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001). CONCLUSION: High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC.
Aged
;
Aged, 80 and over
;
Biological Markers/blood
;
C-Reactive Protein/*metabolism
;
Female
;
Humans
;
Kaplan-Meier Estimate
;
Lung Neoplasms/*blood/*mortality
;
Male
;
Middle Aged
;
Predictive Value of Tests
;
Prognosis
;
Small Cell Lung Carcinoma/*blood/*mortality
7.Analysis of 41 cases of primary hypervascular non-small cell lung cancer treated with embolization of emulsion of chemotherapeutics and iodized oil.
Lingfei LUO ; Hongwu WANG ; Hongming MA ; Hang ZOU ; Dongmei LI ; Yunzhi ZHOU
Chinese Journal of Lung Cancer 2010;13(5):540-543
BACKGROUND AND OBJECTIVETranscatheter arterial chemotherapy and embolization is the main method in the treatment of lung cancer, but most of the reports do not study individually to small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), hypovascular and hypervascular lung cancer. The pre-embolization perfusion of hemotherapeutics is still being used routinely and seldom report to iodized oil embolization. The article summarized the quality of life after the treatment, clinical efficiency, survival time and complications to evaluate the clinical effect of primary hypervascular NSCLC treated with embolization of emulsion of chemotherapeutics and iodized oil.
METHODSThe study totally analyzed 41 cases which confirmed by pathology and follow up study from January, 2008 to January 2009. The CT scan with IV contrast demonstrates over moderate enhanced lesion which indicate hypervascular. Within the 41 cases, 23 cases of central, 18 cases of peripheral. Suqamous carcinoma 21 cases, adenocarcinoma 15 cases and squamoadenocarcinoma 5 cases. Stage IIIb 34 cases, stage IV 7 cases. Superselective incubation with microcatheter under DSA, to embolize the capillary bed with liquefied iodized oil and the emulsion of pharmorubicin, to embolize the supply artery of the tumor with gelatin foam microparticle. The liquefied iodized oil 5 mL-10 mL, pharmorubicin 10 mg-30 mg. The longest follow up is 12 months and to compare with the references of 2007-2009.
RESULTSThe KPS is widely acclaimed after the treatment (P < 0.05), no complete response (CR), 31 cases of partial response (PR), 7 cases of no change (NC) and 3 cases of progressive disease (PD), the total efficiency (CR+PR) is 75.6%. The clinical efficiency (CR+PR+NC) is 92.68%. 33 cases of total survival tome over 12 months (80.48%), IIIb stage 29/34 (85.29%), IV stage 4/7 (57.14%). 1 case with severe complication-spinal injury.
CONCLUSIONTo treat primary hypervascular NSCLC with simple embolization of emulsion of chemotherapeutics and iodized oil is very useful and can avoid the side effect of chemotherapeutics. The key point to avoid spinal injury and other severe complications is to distinguish the spinal aretery and intratumor AV fistula by using superselective incubation with microcatheter under DSA.
Carcinoma, Non-Small-Cell Lung ; blood supply ; mortality ; therapy ; Chemoembolization, Therapeutic ; Emulsions ; Female ; Humans ; Iodized Oil ; administration & dosage ; Lung Neoplasms ; blood supply ; mortality ; therapy ; Male ; Middle Aged
8.18F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer.
Zhen-jiang ZHANG ; Jing-han CHEN ; Long MENG ; Jia-jun DU ; Lin ZHANG ; Ying LIU ; Hong-hai DAI
Chinese Medical Journal 2007;120(2):125-131
BACKGROUNDThe outcome of surgical treatment of non-small-cell lung cancer (NSCLC) remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. (18)F-fluoro-2-deoxy-glucose ((18)F-FDG) uptake on positron-emission tomography (PET) is associated with the aggressiveness of NSCLC. The present study focused on the role of (18)F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC.
METHODSA retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value (SUV(max)), in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients' recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUV(max) and other factors was also analyzed.
RESULTSPatients with SUV(max) more than 11 had a disease-free survival and overall survival shorter than patients with SUV(max) less than 11 in univariate analyses (P < 0.001, P = 0.002). In the multivariate analysis, SUV(max) (dichotomized by 11) was the only significant predictor for tumor recurrence. TNM stage and SUV(max) (dichotomized by 11) were independent predictors for the overall survival. Associations of SUV(max) with p53 overexpression, proliferating cell nuclear antigen (PCNA) labeling index and microvascular density of the tumor were significant in the entire group.
CONCLUSIONS(18)F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood supply ; diagnostic imaging ; mortality ; pathology ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lung Neoplasms ; blood supply ; diagnostic imaging ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Radionuclide Imaging
9.Resection for lung cancer invading the superior vena cava.
Zhong-min PENG ; Jing-han CHEN ; Long MENG ; Jia-jun DU ; Lei WANG ; Lin ZHANG ; Xiao-hang WANG
Chinese Journal of Surgery 2006;44(6):402-404
OBJECTIVETo analyze the feasibility and the value of resection for lung cancer invading the superior vena cava (SVC).
METHODSBetween 1988 and 2005 the data of 31 patients who underwent resection were analyzed retrospectively. The reconstruction was done using simple suture, pericardial patch or prosthetic replacement. Postoperative morbidity, long-term survival were examined using the Kaplan-Meier method (Log rank test) and the COX model for survival.
RESULTSSeventeen squamous cell carcinomas, 8 adenocarcinomas, and 6 undifferentiated small cell carcinomas were resected. There were 13 partial SVC resection, the reconstruction was done using a simple running in 5 patients, and a pericardial patch in 8 patients. Eighteen patients underwent complete resection of SVC with prosthetic replacement. The time of clamping the SVC system was from 8 to 35 minutes for complete resection patients, while the time was from 3 to 15 minutes for partial resection patients. One patient didn't clamp the SVC. Postoperative morbidity and mortality were 48% and 0%, respectively. One, 3 and 5-year survival rates were 61%, 33% and 21%, respectively, with median survival at 31 months. Survival rate of patients with N2 disease was obviously lower than those with localized (N0/N1) nodal disease (chi2 = 14.3, P = 0.000), the median survival was 42 and 13 months respectively. There were no significant effects on overall survival with pathologic features and surgery methods. Survival rate of patients with induction chemotherapy before operation or intraoperative chemotherapy was higher than those received direct surgery (chi2 = 5.0, P = 0.025), the median survival was 39 and 14 months respectively.
CONCLUSIONSThe resection of the SVC for involvement by lung cancer can be performed in selected patients, especially for those with localized (N0/N1) nodal disease. Induction chemotherapy should be performed.
Adult ; Aged ; Blood Vessel Prosthesis Implantation ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; mortality ; pathology ; surgery ; Male ; Middle Aged ; Pneumonectomy ; methods ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Vascular Neoplasms ; mortality ; secondary ; surgery ; Vena Cava, Superior ; pathology
10.The Relationship between the Serum Intercellular Adhesion Molecule-1 Level and the Prognosis of the Disease in Lung Cancer.
Hun Sub SHIN ; Chan Hee JUNG ; Hyun Duk PARK ; Seung Sei LEE
The Korean Journal of Internal Medicine 2004;19(1):48-52
BACKGROUND: Adhesion molecules are related to cell-to-cell interaction and inflammatory interaction. In addition, adhesive interactions between tumor cells and adjacent cells and/or extracellular matrix play important roles in the complex process of tumor growth and development. Among these adhesion molecules, expression of intercellular adhesion molecule-1 (ICAM-1) has been identified in colon cancer, bladder cancer, lung cancer, melanoma, pancreatic cancer and hepatocellular carcinoma. In the current study, we analyzed serum ICAM-1 concentrations to investigate the relationship between the serum ICAM-1 level and prognosis in patients with lung cancer METHODS: Serum ICAM-1 was measured in 84 patients with lung cancer according to the pathologic type and clinical stage using the ICAM-1 ELISA kit. The Kaplan-Meier method was used to analyse survival time. RESULTS: There was no difference in serum ICAM-1 concentration among the different stages of lung cancer. Furthermore, there was no difference observed between histologic tumor type with regard to serum ICAM-1 concentration. Although the difference was not significant, the overall survival times of patients with a low serum ICAM-1 concentration (< 306 ng/mL) was longer than that of patients with a high concentration (> or=306 ng/mL) in non-small cell lung cancer patients. CONCLUSION: These results suggest that high levels of serum ICAM-1 reflect poor prognosis for patients with non-small cell lung cancer.
Aged
;
Carcinoma, Non-Small-Cell Lung/*blood/mortality/pathology
;
Carcinoma, Small Cell/*blood/mortality/pathology
;
Female
;
Human
;
Intercellular Adhesion Molecule-1/*blood
;
Lung Neoplasms/*blood/mortality/pathology
;
Male
;
Middle Aged
;
Neoplasm Staging
;
Prognosis
;
Survival Analysis

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