Combination Of CT And SMRP In Diagnosis Of Early Malignant Pleural Mesothelioma In Rats

Objectives:1.To analyze the CT plain and enhanced manifestations of malignant pleural mesothelioma and explore the value of CT examination in the diagnosis and differential diagnosis of malignant pleural mesothelioma.2.To measure the expression of SMRP in rats with malignant pleural mesothelioma and analyze the expression differences of MPM in different stages,pathological types and differentiation degrees.3.To explore the value of combination CT examination and SMRP to improve the early diagnosis of MPM,providing experimental basis and theoretical basis for clinical screening of high-risk groups with a history of asbestos exposure.Methods:1.To establish the animal model of malignant pleural mesothelioma in rats:120 SD rats(60 male and 60 female)with weight 100-120g were divided into three groups,experimental group with 100 rats:injected with crocidolite suspension from the right second intercostal to pleural cavity with the dosage of 20mg/ml one time and a total of two times with 40mg,negative control group with 10 rats:injected with sterile saline in the same way and dosage and blank control group with 10 rat:no treatment.2.CT examination:CT plain and enhanced scanning was performed in the 3rd and 6-14th month after tumor induction.Scanning equipment:PHILIPS 128-slice spiral CT.Scanning parameters:tube voltage with 100kV,tube current 100mAs,collimator 64x0.625mm,pitch 0.992,rotation time 0.5s,thickness 1.0mm.The contrast agent was iodoprolamine injection with a flow rate of 0.2ml/s and a total volume of 3ml.CT findings were analyzed including pleural thickening,mediastinal changes,intrapulmonary changes,invasion,lymph node and bone metastasis,pleural effusion.Moreover,CT staging was evaluated according to the 2018 guidelines for the diagnosis and treatment of malignant pleural mesothelioma.The diagnostic value of CT examination for different stages was compared.3.Quantitative determination of SMRP:SMRP concentration was determined by ELISA and the serum from tail vein was collected for determination,including determination of tumor before induction,the first,second,third and 6-14th months after tumor induction.To compare the MPM expression differences of SMRP in different stages,pathological types and different differentiation degrees.Moreover,the value of combination CT and SMRP in early diagnosis of MPM was investigated.4.To explore the value of combination CT examination and SMRP to improve the early diagnosis of MPM through ROC curve.5.Pathological examination:The suspicious tumor tissues were sampled,stained and performed immunohistochemical analysis.The tumor pathological stages were recorded and the degree of tumor differentiation and pathological subtypes were analyzed.Results:1.In the experimental group,72 cases of malignant pleural mesothelioma were induced,with a 75%induction rate,4 cases of lung cancer,4 cases of death,and 20 cases of no tumor.Seventy-two cases of pleural mesothelioma included 21 cases of epithelial type(29.2%),37 cases of sarcoma type(51.4%),and 14 cases of mixed type(19.4%).There were no statistically significant differences in tumor occurrence time,gender and body weight among different types(P>0.05).There was no tumor in the negative control group and the blank control group.Degree of differentiation:low differentiation was 58 cases(80.6%),high differentiation 14 cases(19.4%).There was no significant difference between MPM differentiation degree and tumor occurrence time,gender and body weight among different types(P>0.05).2.Tumor stage:pathological stage:T stage included T1 stage(T1a stage:0 cases and T1b stage with 14 cases),T2 stage 23 cases,T3 Stage 28 cases,T4 stage 7 cases.N stage included 45 cases of stage N0,16 cases of N1 stage,8 cases of N2 stage and 3 cases were indistinct.M stage included 51 cases of M0 stage,8 cases of M1 stage,but 13 cases were indistinct.For clinical stage,there were 18 cases in early stage,25 in middle stage and and 7 in late stage.3.CT examination can show pleural lesions,mediastinal lesions,intrapulmonary lesions and bone changes.Fifty cases(69.4%)was diagnosed of MPM by CT,5 cases(6.9%)of non-MPM and 17 cases(23.7%)of no lesions among 72 MPM.Diagnostic value of CT for MPM:AUC was 0.65,sensitivity and specificity were 64.5%and 71.2%,respectively.The AUC of T stage was 0.85,the sensitivity and specificity were 53.5%and 61.6%,respectively.The AUC of N stage was 0.82,and the sensitivity and specificity were 72.5%and 75%,respectively.The AUC of M stage was 0.85,and the sensitivity and specificity were 100%and 95%,respectively.The AUC of T1 and T2 were 0.68,0.82,the sensitivity and specificity were 35.7%,43.5%and 44.4%?57.2%,respectively.The AUC of T3 and T4 was 0.95,1.00,and the sensitivity and specificity were 89.3,100%%and 90%,100%,respectively.This indicated that the diagnosis efficiency of stage 1 and 2 was poor,while that of stage 3 and 4 was high.The diagnosis efficiency of N and M stages was high.4.The difference in SMRP expression in different time periods was statistically significant(F=161.07,P<0.05).Further pair comparison showed no difference in SMRP before induction in the three groups,no difference in the negative control group and the blank control group in different time periods.In the experimental group,there were statistical differences before and after induction,and there was no difference between the groups in the first month and second months after induction,and there were statistical differences between the groups in the third month and the sixth months.In the experimental group,SMRP expression increased gradually with the time.SMRP expression in negative control group and blank control group was low and did not change significantly with the time.5.The difference of SMRP expression in different pathological stages between the experimental group,the negative control group and the blank control group were statistically significant(F=324.45,P<0.05).There was no significant difference between the negative control group and the blank control group(P>0.05),and there was no significant difference between the pleurisy group and the group with normal pleura in the negative control group(P>0.05).In the experimental group,the expression level of MPM SMRP in different stages was significantly different between groups(P<0.05).The higher the stage,the higher the expression level of SMRP.There were statistically significant differences in the expression levels of SMRP in N0,N1 and N2 stage of lymph node metastasis in the experimental group(F=14.92,P<0.05)and there was no statistically significant difference in N1 and N2 level between the two groups.There was statistically significant difference in M0 and M1 expression in the experimental group(t=214.31,P<0.05).6.The difference of SMRP expression in different clinical stages of MPM was statistically significant(F=341.63)P<0.05).The earlier MPM was,the lower the SMRP expression was.7.Correlation analysis between pleural thickness and SMRP expression:there were statistically significant differences in SMRP expression between groups with different degrees of pleural thickening in the third month and sixth month(F=933.67,150.98,respectively,both P<0.05).Spearman correlation analysis was used to analyze the relationship between pleural thickness and SMRP expression.The correlation coefficients in the third month and sixth month were 0.90 and 0.93,respectively,and the F value was 0.01 and 0.007<0.05,showing a strong correlation.With the increase of pleural thickness,SMRP expression gradually increased.8.Comparison of SMRP expression differences among different pathological types of MPM:SMRP expression differences among different pathological types of MPM were not statistically significant(F=1.39,P>0.05),indicating that SMRP expression had nothing to do with pathological types.9.Comparison of SMRP expression differences among MPM with different degrees of differentiation:SMRP expression differences among MPM with different degrees of differentiation were statistically significant(t=193.04,P<0.05),and the SMRP expression of MPM with low differentiation was higher than that with high differentiation.10.Diagnostic value of SMRP for MPM:for MPM T1,AUC=0.83,the optimal threshold was 1.90mmol/ml,the sensitivity and specificity were 100%and 88.2%,respectively.For T2 AUC=0.86,the optimal threshold was 4.53mmol/ml,and the sensitivity and specificity were 100%and 85.7%,respectively.For T3,AUC=0.92,the optimal threshold was 8.73mmol/ml,and the sensitivity and specificity were 71.4%and 100%,respectively.For T4,AUC=0.85,the optimal threshold was 11.97mmol/ml,and the sensitivity and specificity were 87.5%and 100%,respectively.11.Value of CT combined with SMRP in the diagnosis of MPM:for T stage,AUC=0.97,sensitivity and specificity were 90.5%and 92.5%,respectively,which were significantly higher than that of CT diagnosis of MPM(AUC=0.85,sensitivity and specificity were 53.5%and 61.6%,respectively).For N stage,AUC=0.96,sensitivity and specificity were 87.5%and 92.5%,respectively,significantly higher than that of CT diagnosis of MPM(AUC=0.82,sensitivity and specificity were 72.5%and 75%,respectively).For M staging,AUC=0.95,with sensitivity and specificity of 100%and 98%,respectively,higher than that for CT diagnosis of MPM(AUC=0.85,with sensitivity and specificity of 100%and 95%,respectively).Conclusion:1.In this study,the animal model of malignant pleural mesothelioma in rats induced by thoracic injection of asbestos was used,and the induction rate was 75%,including epithelial type,sarcoma type and mixed type.The development of MPM was observed by CT.It can provide a reliable tumor model for MPM research.2.CT examination was of certain value in the staging of malignant pleural mesothelioma,while had a little value in the diagnosis of early pleural mesothelioma,and of great value in the diagnosis of middle and late stages of tumors.3.SMRP expression was different in different stages of MPM,SMRP expression level was positively correlated with stage,the higher the stage was,the higher the SMRP expression was.SMRP expression was different in lymph node metastasis and distant metastasis.This indicates that SMRP can reflect tumor stages,and also suggests that SMRP may be involved in the process of tumor occurrence and development,as well as tumor invasion and metastasis.SMRP expression of MPM in different differentiation levels was different,with low differentiation and high expression,suggesting that SMRP could indirectly reflect the malignant degree of MPM and tumor stage.Pleural thickness can be used as a reference for tumor prognosis,and SMRP expression varies in different degrees of pleural thickness,indicating that SMRP can be used as an indicator to indirectly reflect tumor prognosis and evaluate tumor treatment response.4.Detection of serum SMRP expression can provide experimental basis and theoretical basis for early detection and early diagnosis of MPM and biological targeted therapy for high-risk population with a history of asbestos exposure.5.Combination CT and SMRP had a higher diagnostic value for early diagnosis of MPM,which was significantly higher than that of CT alone.It indicated that imaging examination combined with serological examination was feasible for early diagnosis of MPM.