• The Korean Journal of Cytopathology
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• v.19 no.2
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• pp.126-135
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• 2008

Malignant mesothelioma (MM) is a highly lethal neoplasm arising in pleura and the peritoneum and a rapid and accurate diagnosis is crucial for treatment of the disease. However, the sensitivity of cytological analysis using pleural or ascitic fluid is relatively low, yielding an accurate diagnosis in only $32{\sim}79%$ of cases. We tested the diagnostic value of epigenetic alterations in body fluid cytology as a supplement to conventional methods. Paraffin-embedded tissue blocks from 21 MM patients and associated body fluid cytology slides considered no evidence of malignancy were used to test for epigenetic alteration. Using methylation-specific PCR, we detected methylation of RASSF1A and p16 in 47.6% (10/21) of both surgically resected tumor samples, respectively. Body fluid samples of MM also showed abnormal methylation of RASSF1A and p16INK4a genes in 38.1% (8/21) and 33.3% (7/21) of cases. The concordance in the rates of RASSF1A and p16INK4a gene-methylation abnormalities determined from cytology samples and tissue samples were 61.9% (13/21) and 66.7% (14/21), respectively. Combining both genes increases the sensitivity of the test to 57.1 % (12 of 21) of cases. Our results suggest that testing for methylation abnormalities in selected individual genes or gene combinations has diagnostic value as an alternative or adjunct method to conventional cytological diagnosis.

• Journal of Chest Surgery
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• v.55 no.5
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• pp.405-412
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• 2022

Background: Malignant pleural mesothelioma (MPM) is an aggressive pleural malignancy, and despite all multimodal treatment modalities, the 5-year overall survival rate of patients with MPM is less than 20%. In the present study, we aimed to analyze the surgical and prognostic outcomes of patients with MPM who received multimodal treatment. Methods: In this retrospective, single-center study, the records of patients who underwent surgery for MPM between January 2010 and December 2020 at our department were reviewed retrospectively. Results: Sixty-four patients were included in the study, of whom 23 (35.9%) were women and 41 (64.1%) were men. Extrapleural pneumonectomy, pleurectomy/decortication, and extended pleurectomy/decortication procedures were performed in 34.4%, 45.3%, and 20.3% of patients, respectively. The median survival of patients was 21 months, and the 5-year survival rate was 20.2%. Advanced tumor stage (hazard ratio [HR], 1.8; p=0.04), right-sided extrapleural pneumonectomy (HR, 3.1; p=0.02), lymph node metastasis (HR, 1.8; p=0.04), and incomplete multimodal therapy (HR, 1.9; p=0.03) were poor prognostic factors. There was no significant survival difference according to surgical type or histopathological subtype. Conclusion: Multimodal therapy can offer an acceptable survival rate in patients with MPM. Despite its poor reputation in the literature, the survival rate after extrapleural pneumonectomy, especially left-sided, was not as poor as might be expected.

• Molecules and Cells
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• v.40 no.8
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• pp.567-576
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• 2017

The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4169-4173
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• 2016

Background: Mesotheliomas are relatively rare tumors in Lebanon. The only previous study goes back to 14 years ago, when we published epidemiological characteristics of mesotheliomas in Lebanon, showing that the pleural location accounted for the vast majority of cases, with clear evidence of asbestos exposure from the Eternit factory of Chekka region. The objective of this current study was to estimate the incidence of mesothelioma in the past decade and to identify its epidemiological, clinical and therapeutic characteristics, making comparisons with our first study published in 2001. Materials and Methods: Between 2002 and 2014, patients diagnosed with malignant mesothelioma at Hotel-Dieu de France University Hospital were investigated. Epidemiological data focusing on asbestos exposure history were collected from medical records and interviews with the families. Results: A total of 26 patients were diagnosed with mesothelioma, 21 of which were successfully investigated. The mean age of these 21 patients is 62.5 (19-82). Only 3 (14.29%) are women. 18 (85.71%) were smokers. Among the 21 available mesotheliomas, 15 (71.4%) are pleural, while 5 (23.8%) are peritoneal and 1 (4.8%) pericardial. Only 60% of patients with pleural mesothelioma and 50% of those with an obvious exposure to asbestos lived and/or worked in Chekka region. The mean time of asbestos exposure in patients with mesothelioma is 24.5 (1-50) years and the mean latency is 37.4 (4-61) years. Of the 21 patients, 10 (47.6%) underwent surgery during their treatment, 16 (76.2%) received chemotherapy and 3 (14.3%) received best supportive care. Conclusions: Compared to the previous study (1991-2000), substantial changes in the epidemiology of mesothelioma in Lebanon were observed, such as an increase in peritoneal localizations and a lower correlation with Chekka region asbestos contamination.

• Journal of Chest Surgery
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• v.2 no.1
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• pp.49-54
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• 1969

Four cases of pleural mesothelioma were treated surgically. The tumors from all cases were microscopicaly malignant, although only in one case the tumor was found to be diffuse in growth. The diagnosis made before operation were exudative pleurisy, empyema or lung cancer with no tumor cells found in examination of pleural fluid, sputum or the specimen of pleuraI biopsy. In two cases only the tumors were resected, and in other two cases pneumonectomy and pleuropneumonectomy were performed. Irradiations added in two cases postoperatively were found not to be beneficial. Postoperative recurrence of tumor growth were found in three cases within two months after surgery, and in one case no evidence of recurrence was noted four and a half months after resection of the tumor.

• Journal of Chest Surgery
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• v.33 no.12
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• pp.982-987
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• 2000

미만성 악성 중피세포종은 예후가 불량한 드문 암종으로, 아직까지 적절한 병기 분류가 없고, 병리 조직학적인 진단이 쉽지 않다. 치료에 대해서 논쟁이 많지만 선택된 환자에서 늑막 폐절제술을 시행하고 보조적인항 화학요법과 방사선 요법이 생존 기간을 연장시킬 수 잇다. 저자들은 1992년 6월부터 7년간 미만성 악성 중피세포종 환자 4례에서 늑막 폐절제술을 시행하였으며 수술후 조기 사망은 없었다. 3례의 환자에서 수술후 보조요법을 시행할 수 있었다(보조 화학요법 2례, 보조 화학요법 및 방사선 치료 1례). 그러나 한 예에서는 수술후 발생한 심장염전에 의한 저산소성 뇌손상 및 농흉으로 인하여 보조용법을 시행할 수 없었다. 저자들은 저자들의 늑막 폐 절제술의 경험 및 미만성 악성 중피세포종에 대한 논란이 되는 점을 문헌고찰과 함께 보고하는 바이다.

• Journal of Chest Surgery
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• v.37 no.3
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• pp.228-234
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• 2004

Primary cardiac tumors are rare disease and they present nonspecific symptom. They are divided in benign and malignant tumors and require surgical therapy and/or additional therapy. From March 1995 to March 2003, twenty one patients were diagnosed as having primary cardiac tumors. We analysed them retrospectively in terms of various perioperative factors and early and late results. 6 men and 15 women and their average age was 45.44$\pm$18.76. Pathology revealed eighteen benign (fourteen myxoma, two fibroelastoma, one hemangioma and one paraganglioma) disease and three malignant (one angiosarcoma, one mesothelioma and one myxofibrosarcoma) disease. There was one (myxoma) operative mortality and three late death (hemangioma, angiosarcoma and mesothelioma) during additional therapy and follow up. Surgical treatment of primary cardiac tumor is important and sometimes additional therapy is required but the prognosis of malignant cardiac tumor is still very poor.

• Journal of Chest Surgery
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• v.29 no.12
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• pp.1385-1391
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• 1996

Solitary fibrous tumor of the pleura has been classified as a type of mesothelioma. This tumor have been recently described and distinguished from the mesothelioma, immunohistochemically and elect r om ic ro scop ical 1 y Thls 65 years female was admitted with right chest pain, coughing and dysnea. Chest X-ray and C-T scan showed a huge mass in the right thorax. Right thoracotomy was done and a 12$\times$12$\times$6cm(400gm) sized mass was excised, and the tumor had metastasized to the diaphragm, parietal pleura and lung parenchyma. Microscopically, the tumor Is composed of oval-round and plump spindle cells with diffuse pattern. There are occasional mitoses (311 OHPFS) and invasion to lung parenchyma. The immunohistochemical and electromicroscopical findings are consistent with malignant solitary fibrous tumor of the pleura. We experienced a case of pleural malignant solitary fibrous tumor and report this case with the review of literature.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.363-368
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• 2014

Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.

• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.478-487
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• 1999

Background : Differential diagnosis of pleural malignant mesothelioma from secondary metastatic adenocarcinoma is often difficult. A variety of pathologic techniques have been developed to make a differential diagnosis of carcinoma from mesothelioma. Immunohistochemistry detecting diverse antigenic substances such as CEA, Leu-M1, Bn-3, S-100 protein, vimentin, CK and EMA has been claimed to be of value as a panel in the differential diagnosis of adenocarcinoma from mesothelioma. The aim of this study was to investigate the suitable antibodies to distinguish mesothelioma from metastatic adenocarcinoma and establish candidate markers in a panel. Methods : Complete, one-hour immunohistochemical staining using antibodies against cytokeratin (CK), epithelial membrane antigen(EMA), S-100 protein, vimentin, B72-3, Leu-M1, and carcino-embryonic antigen(CEA) was applied to cell blocks from 7 mesotheliomas and 7 adenocarcinomas which were confirmed by electron microscopic and histpathologic methods. Results : All adenocarcinomas and 71.4% of mesotheliomas expressed the cytokeratin and EMA. S-100 protein and vimentin were expressed in 57.1% and 42.9% of mesotheliomas and 14.3% and 28.5% of adenocarcinomas, respectively. B72-3 was expressed in all adenocarcinomas, but in none of mesotheliomas. Leu-M1 was positive in 71.4% of the adenocarcinoma and 14.3% of the mesotheliomas. CEA was positive in all adenocarcinomas and 42.9% of mesotheliomas. Leu-M1 and B72-3 were coexpressed in 71.4% of adenocarcinomas but in none of mesothelioma. B72-3 and CEA were coexpressed in all adenocarcinomas, but in none of mesotheliomas. Conclusion : We concluded that B72-3 immunohistochemistry or panel staining of B72-3 and CEA could be recommanded for the differential diagnosis of pleural mesothelioma from metastatic adenocarcinoma.