Application Of Pleural Tumor Cell Immune Magnetic Bead Negative Enrichment And Multidisciplinary Collaboration In The Diagnosis And Treatment Of Lung Cancer

ObjectiveThe thesis consists of two parts:Part I Use the method of immunomagnetic beads negative to enrich malignant pleural tumor cells,then to detect telomerase activity of tumor cells and investigate its roles in the diagnosis, treatment and prognosis of patients with lung cancer; Part Ⅱ to explore the impacts of the multi-disciplinary team (MDT) model on the average length of stay and hospital expenses in patients with lung cancer.MethodsPart Ⅰ:This study was designed as an open-label and single-center trial performed in Subei People’s Hospital. From May2011to February2014,42patients with lung cancer associated with malignant pleural effusion were enrolled in this study.31cases of them finished the study while11cases escaped. Blood and pleural effusion samples of patients were obtained before and after chemotherapy. By using the negative enrichment method of immunomagnetic beads, we enriched the tumor cells in pleural effusion and blood sample separately and counted the tumor cells in each of them, then detected the telomerase activity of the tumor cells in pleural effusion after enriching, as well as tumor markers (serum and pleural fluid CEA) and pleural fluid LDH indicators, and collected the imageology material (CT or PET-CT) of each patient before and after chemotherapy. Data were analyzed by using x2test, T test and linear regression analysis.Part Ⅱ:From December2011to December2013, we selected97cases according with enterer and elimination standard discussed by MDT as the trial group and the average aged was61±9years old, and other97cases had not been discussed as the control group. All the patients were firstly diagnosed as lung cancer in Subei People’s Hospital and the average aged was63±10years old. The length of stay, hospital expenses, stages of tumor, types of tumor, ZPS score, payment, smoking history, sex and age of all the patients were collected. Data were analyzed by using x2test, T test and multi-factor stepwise regression analysis.Results Part Ⅰ:1.The expressions of CEA, LDH and RTA were high in malignant pleural effusion in base line, and the positive rate of telomerase was87.07%(27/31); The levels of CEA were high in serum, and CTCs detection rate was93.33%(14/15) and the average count was12.2/7.5ml.2. The sensitivity priority of various makers to malignant pleural effusion was:telomerase activity (87.07%)> pleural fluid LDH (83.87%)> pleural fluid CEA (80.65%) The diagnostic sensitivity of combined detection were higher than that of single assay, and the diagnostic sensitivity of simultaneous determination in three markers reached96.77%and significantly higher than that of single assay. The sensitivity priority of various makers to lung cancer was:CTCs (93.33%)> telomerase activity (86.67%)> serum CEA (66.67%), The diagnostic sensitivity reached100%when these marker joint and showed statistically significant compared with the serum CEA (P<0.05).3. The RTA (38.02%±0.47vs29.14%±0.41, p<0.05) and the serum CEA expression decreased (304.11±342.45vs138.66±90.36,P>0.05)after chemotherapy, telomerase activity changes before and after chemotherapy was consistent with tumor markers CEA and imaging. Even in some patients, the changes of telomerase activity are earlier than imaging changes.4.The median survival time of all patients was8.57months, which reached PFS19cases(5.89months), OS18cases(8.72months). Analysis showed the telomerase activity has negatively correlated with chemotherapy response.(r=-0.699,p=0.001).Part II:1. Compared the trial group with the control group in lung cancer, there were no differences between the two groups in constituent ratio of stages, types, ZPS score, payment, smoking history, sex and age.2. The average length of stay and hospital expenses of lung cancer patients were much lower in the trial group (13303vs16553, p<0.01;10.33vs12.49, p<0.05), especially in the process of the first clinical hospitalization (15953vs19485,p<0.05;12.71vs14.75,p<0.05).3. The average length of stay and the stages of lung cancer are the main factors affecting the average hospital expenses. For addition, the average length of stay and hospital expenses had trended lower in different stagesin the trial group except the limited stage of small cell lung cancer. 4. Compared to the control group in lung cancer, the gap between the hospital costs and length of stay at stage Ⅰ a-Ⅲa and Ⅲb-Ⅳ patients was narrow.ConclusionPartⅠ:1.This study furtherly proved the high sensitivity of detecting the telomerase activity after enriching pleural effusion by the immunomagnetic beads negative enrichment method;2.Combined with the detection of CEA and LDH in plerual effusion, the detection of the telomerase activity of tumor cells enriched from pleural effusion by the immunomagnetic beads negative enrichment method can also improve the sensitivity of diagnosing MPEs. CTCs is a sensitive maker to advanced lung cancer, and the combination of detecting serum CEA, CTCs and the telomerase activity of pleural effusion is also helpful to the diagnosis of lung cancer.3. Monitoring the change of telomerase activity before and after chemotherapy may be useful to assess the response of lung cancer to the treatment in real time. The change of telomerase activity before and after chemotherapy was consistent with the change of tumor markers CEA and imaging. Even in some patients, the change of telomerase activity is earlier than imaging change.4.Telomerase activity is negatively correlated with chemotherapy response in lung cancer.Part Ⅱ:1. MDT meeting model is useful to cut down the cost of hospitalization of lung cancer patients and to shorten the length of stay, and the trendency is more apparent in the process of the first clinical hospitalization;2. The stages of lung cancer are the main factors affecting the average hospital expenses and length of stay, Patients of different stages may benefit from MDT meeting model to varying degrees.3. MDT model standardized lung cancer diagnosis and treatment processes, on the basis of reducing the hospital costs and length of stay, and further reduced the gap between the two hospital indexes of lung cancer patients at Ⅰ a-Ⅲa and Ⅲb-Ⅳ stage, and patients of stage Ⅰ a-Ⅲa benefit more.4. Compared to the control group in lung cancer, the gap between the hospital costs and length of stay at stage Ⅰ a-Ⅲa and Ⅲb-Ⅳ patients was narrow.