الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 245 |  |  |
| | | from | 245 | | |
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive tumour of mesothelial origin that occurs after a long latency period following asbestos exposure often comprising several decades. MPM occurs mostly in the pleura (>75%) and less often in the peritoneum (10–20%) or pericardium (1%).
Most patients present with a pleural effusion as first symptom.
Diagnosis is based on testing of multiple immunohistochemical markers of biopsies or cytological samples, and soluble biomarker analysis of pleural effusion to distinguish MPM from other lung malignancies. Among soluble biomarkers, hyaluronan and mesothelin are the best characterized biomarkers for diagnosis of MPM.
Mesothelin is a physiologically expressed membrane-bound peptide on the surface of normal mesothelial cells and is found expressed in various cancers, including malignant pleural mesothelioma, pancreatic, ovarian cancers, sarcomas, and in some gastrointestinal and pulmonary carcinoma.
The aim of the present work is to evaluate the diagnostic value of soluble mesothelin level in blood and pleural fluid in patients with pleural malignancies, and to assess whether this marker can replace the histochemichal studies in the differentiation between different types of pleural malignancies.
The study included 48 patients with pleural effusion due to different causes. The cases were classified according to the results of final histopathological diagnosis into three equal groups, each of 16 patients: group A (mesothelioma), group B (metastatic malignancy) and group C (transudative effusion).
The cases in group A and B were included after proving that the pleural effusion was exudative in nature based on Light’s criteria. The definite cytological examination of pleural fluids and histopathological diagnosis and immunophenotyping of pleural biopsies which were taken by thoracoscopy, or ultrasound guided revealed malignant changes consistent with malignant pleural mesothelioma (group A) and revealed malignant changes other than MPM (group B).
group C included cases diagnosed as transudative pleural effusion due to cardiac, hepatic, or renal causes. Patients were considered to have transudative pleural effusion according to Light’s criteria with evidence of presence of cardiac, hepatic, or renal dysfunction.
The subjects with any of the following criteria were excluded; patients with exudative pleural effusion secondary to any pathology other than malignancy, bleeding tendency or presence of co-morbid diseases that prevent surgical interventions in patients with exudative pleural effusion, such as severe decompensated heart failure.
Detailed history, clinical examination, laboratory investigations (including complete blood picture (CBC), renal and liver function tests, and bleeding profile), and chest radiography were conducted to all of them.
Pleural fluid was examined by using Light’s criteria. Cytological examination of pleural fluid and histopathological examination of pleural biopsies were done in patients with exudative pleural effusion.
The level of Mesothelin was assessed in serum and pleural fluid by using enzyme-linked immune-sorbent assay.
Dyspnea was found in all groups, while cough, chest pain and toxic symptoms were significantly associated with mesothelioma and metastatic malignant groups than transudative group, P = 0.004, 0.01 and 0.03, respectively.
The transudative group was significantly presented with bilateral effusion, P < 0.001.
In mesothelioma groups, pleural nodules and septation were more prominent than in metastatic group, P < 0.001 and 0.02, respectively.
The malignant groups: mesothelioma and metastatic malignancy were diagnosed using thoracoscopic biopsy mainly and ultrasound pleural biopsy. The final pathology results showed mesothelioma and metastatic adenocarcinoma
SMRP levels in serumand fluid were measured for all groups, the median SMRP level in group (1) in which all subjects were diagnosed as having malignant pleural mesothelioma was 6.25nM/L and 7.41 nM/L, while in group (2) which was composed of patient with malignant pleural effusion caused by causes other than malignant pleural mesothelioma the median was 2.95 nM/L and 3.48 nM/L, and in group (3) which was transudate pleural effusion the median was 0.73nM/L and 0.88 nM/L.
These results denoted that there was a great difference between the studied groups with highly significant statistical increase malignant groups (mesothelioma and metastatic tumors) than transudative groups, P < 0.001 for both. Moreover, the level of SMRP in blood and fluid were significantly higher in mesothelioma than in metastatic malignancy groups, P < 0.001 for both.
The diagnostic utility of SMRP in blood and fluid in diagnosis of mesothelioma is excellent, the AUC were 96 and 99% respectively, P < 0.001 for both. The sensitivity, specificity, PPV and NPV at cutoff value > 0.67 and 1.66 respectively equal to 100; 100, 94; 94, 78; 78 and 100; 100% respectively.
The Receiver Operating characteristic (ROC) curve of SMRP in blood and effusion showed excellent performance in diagnosis of mesothelioma, AUC= 96 and 99% respectively.
The diagnostic utility of SMRP in blood and fluid in diagnosis of metastatic malignancy is excellent, the AUC were 94 for both, P < 0.001 for both. The sensitivity, specificity, PPV and NPV at cutoff value > 0.57 and 0.845 respectively equal to 100; 100, 94; 75, 78; 47 and 100; 100% respectively.
The ROC curve of SMRP in blood and effusion showed excellent performance in diagnosis of metastatic malignancy, AUC= 94 % for both.
The diagnostic utility of SMRP in blood and fluid in differentiation between mesothelioma and metastatic tumor is very good, the AUC were 80% for both, P =0.004 for both. The sensitivity, specificity, PPV and NPV at cutoff value > 02.695 and > 4.96 respectively equal to 88; 81, 75; 75, 43; 42 and 96; 95% respectively.
The ROC curve of SMRP in blood and effusion showed very good performance in differentiation between mesothelioma and metastatic malignancy, AUC= 80 % for both.