• 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.25 no.10
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• pp.1102-1106
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• 1992

A 66-year-old male patient was admitted due to chest pain and dyspnea of 1 year duration, He had history of treatment for tuberculosis and pleurisy, about 40 years ago. At another hospital the patient underwnt closed thoracostomy drainage for six months, and thereafter the symptom gradually aggrevated. Under the diagnosis of chronic tuberculous empyema, decortication was performed. The peel attached to the posterolateral aspect of chest wall, there was an area of soft tissues with pale-brown discoloration, extending to intercostal muscles, but sparing overlying muscles. The biopsy specimen of the lesion was pathologically diagnosed as diffuse, large T-cell non-Hodgkin`s lymphoma. A review of the literature showed that malignant lymphoma of this type have been reported exclusively from Japan but never from other countries including Korea. After 1 year of followup period, the patient is well and stable.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.171-181
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• 2001

Background : Angiogenesis is an essential process for the growth and metastatic ability of solid tumors. One of the key factors known to be capable of stimulating tumor angiogenesis is the vascular endothelial growth factor (VEGF). The serum VEGF concentration has been shown to be a useful parameter related to the clinical features and prognosis of lung cancer and has been recently applied to a the malignant pleural effusion showing a correlation with the biochemical parameters. The VEGF has been shown to play a role in the inflammatory diseases, but rarely in the tuberculosis (TB). The serum and pleural fluid VEGF levels were measured in patients with lung cancer and TB. Their relationship with the clinical and laboratory parameters and repeated measurement 3 months after various anticancer treatments were evaluated to assess the utility of the VEGF as a tumor marker. Methods : Using a sandwich enzyme-linked immunosorbent assay, the VEGF conoentration was measured in both sera and pleural effusions collected from a total of 85 patients with lung cancer, 13 patients with TB and 20 healthy individuals. Results : The serum VEGF levels in patients with lung cancer ($619.9{\pm}722.8pg/ml$) were significantly higher than those of healthy controls ($215.9{\pm}191.1pg/ml$), However, there was no significant difference between the VEGF levels in the lung cancer and TB patients. The serum VEGF levels were higher in large cell and undifferentiated carcinoma than in squamous cell carcinoma and adenocarcinoma. The serum VEGF levels of lung cancer patients revealed no significant relationship with the various clinical parameters. The VEGF concentrations in the malignant effusion ($2,228.1{\pm}2,103.0pg/ml$) were significantly higher than those in the TB effusion ($897.6{\pm}978.8pg/ml$). In the malignant pleural effusion, the VEGF levels revealed significant correlation with the number of red blood cells (r=0.75), the lactate dehydrogenase (LDH)(r=0.70), and glucose concentration (r=-0.55) in the pleural fluid. Conclusion : The serum VEGF levels were higher in the lung cancer patients. The VEGF levels were more elevated in the malignant pleural effusion than in the tuberculous effusion. In addition, the VEGF levels in the pleural fluid were several times higher than the matched serum values suggesting a local activation and possible etiologic role of VEGF in the formation of malignant effusions. The pleural VEGF levels showed a significant correlation with the numbers of red blood cells, LDH and glucose concentrations in the pleural fluid, which may represent the tumor burden.

• IMMUNE NETWORK
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• v.2 no.3
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• pp.142-149
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• 2002

Background: Our previous study showed that purified protein derivative (PPD)-stimulated pleural mononuclear cells (PMC) from tuberculous pleurisy (Tbp) produced significantly more $IFN-{\gamma}$ (10- to 70-fold) after in vitro PPD stimulation than freshly isolated pleural cells from malignant pleurisy. The present study was designed to determine whether blocking the CD40-CD40 ligand (CD40L) interaction decreases $IFN-{\gamma}$ production by altering IL-12 levels. Methods: IL-12 and $IFN-{\gamma}$ production after neutralizing anti-CD40L antibody treatment was compared to the efficacy of anti-CD80, anti-CD86, and a combination of anti-CD80 and CD86 (CD80+86) monoclonal antibodies (mAb). These activities were measured by enzyme-linked immunosorbent assays (ELISAs) and reverse transcription-polymerase chain reaction (RT-PCR), after in vitro stimulation with PPO antigen (Ag). Results: Neutralization of CD80, CD86 and CD80+86 did not decrease $IFN-{\gamma}$ and IL-12 production in Tbp-PMC, whereas neutralization of CD40L significantly depressed IL-12 p40 and $IFN-{\gamma}$. In addition, neutralization of CD40L completely inhibited IL-12 p40 and $IFN-{\gamma}$ mRNA expression. Conclusion: The CD40-CD40L interaction might play a major role in IL-12 and $IFN-{\gamma}$ production in Tbp-PMC, thus contributing to protective immunity in human tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.388-396
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• 1998

Background: Etiologic diagnosis of pleural effusion is usually made by clinical characteristics, pleural fluid analysis and pleural biopsy. But, despite careful diagnostic study, the cause of pleural effusion cannot be found in about 20 percent of patients, especially in loculated pleural effusions. Tuberculous pleurisy is one of the most common cause of pleural effusion in Korea. But, pleural fluid culture for Mycobacterium tuberculosis are positive in only 20 to 30 percent of patients and typical pleural biopsy finding in less than 50 percent of patients with this disease. In recent studies, adenosine deaminse(ADA) and its isoenzymes were proposed to be a useful diagnostic tool for differential diagnosis of pleural effusion. We investigated the pattern of ADA and its iscenzyme activities in various cause of pleural effusions to evaluate the diagnostic value of measuring ADA and its isoenzymes. Method: We measured total ADA and its isoenzyme activities in pleural fluid and serum from 54 patients with pleural effusion(25 tuberculous pleural effusion, 10 parapneumonic effusion, 14 malignant pleural effusion, 5 transudative pleural effusion), including 5 loculated tuberculous pleural effusions and 6 loculated parapneumonic effusions. Total ADA activity was measured by the spectrophotometric method and ADA2 isoenzyme activity was measured with same method using EHNA, potent inhibitor of ADA1 isoenzyme activity. Result: Total ADA activity of tuberculous pleural effusion was higher than malignant pleural effusion(p<0.01), but no significant difference was found between tuberculous pleural effusion and parapneumonic effusion(tuberculous pleural effusion: $148.9{\pm}89.9IU/L$, parapneumonic effusion: $129.0{\pm}119.4IU/L$, malignant pleural effusion: $48.7 {\pm}39.7IU/L$). Percentage of ADA2 activity to total ADA activity(ADA2%) of pleural effusion of tuberculous pleurisy was higher than parapneumonic effusion(p<0.05). but no significant difference was found between tuberculous pleural effusion and malignant pleural effusion(tuberculous pleural effusion: $57.2{\pm}10.7%$, parapneumonic effusion: $35.9{\pm}17.8%$, malignant pleural effusion: $60.7{\pm}4.1%$). In loculated pleural effusion, ADA2% of tuberculous pleural effusion was higher than parapneumonic effusion(tuberculous pleural effusion: $53.3{\pm}3.9%$, parapneumonic effusion: $27.8{\pm}7.9%$). Conclusion: Measurement of ADA isoenzyme activity is useful for differentiating tuberculous pleural effusion from parapneumonic effusion, especially in loculated pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.186-192
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• 2005

Background : Diagnosis of tuberculous pleurisy is sometimes difficult using conventional diagnostic methods. We have investigated the utility of pleural fluid cell $IFN-{\gamma}$ production assay in the diagnosis of tuberculous pleurisy. Methods : We prospectively performed pleural fluid cell $IFN-{\gamma}$ production assay in 39 patients with tuberculous pleural effusions (TPE) and in 26 patients with nontuberculous pleural effusions (NTPE) (13 malignant pleural effusions and 13 parapneumonic effusions). Pleural fluid cells were cultured in DMEM media and stimulated with purified protein derivatives (PPD), and phytohemagglutinin (PHA) for 24 hr. The amount of $IFN-{\gamma}$ released in the culture supernatant was quantitated by $IFN-{\gamma}$ ELISA assay. We have also measured adenosine deaminase (ADA) activities and $IFN-{\gamma}$ concentrations in the pleural fluid. Results : 1) The pleural fluid levels of ADA activity and $IFN-{\gamma}$ concentrations were significantly higher in TPE than NTPE (p<0.01). 2) $IFN-{\gamma}$ production in TPE cells stimulated by PPD ($755,266{\pm}886,636pg/ml$) was significantly higher than NTPE cells ($3,509{\pm}6,980pg/ml$) (p<0.01). By considering the fact that $IFN-{\gamma}$ concentrations over 10,000 pg/ml is a criteria for the diagnosis of TBE, sensitivity and specificity of the test were 97.4 and 92.3%, respectively. 3) The ratios of $IFN-{\gamma}$ production by the stimulation with PPD and PHA (PPD/PHA) were significantly higher in TPE cells ($59{\pm}85$) than NTPE cells ($5{\pm}18$)(p<0.01). Considering the criteria for the diagnosis of TBE as PPD/PHA ratio over 5, sensitivity and specificity of the test were 76.9 and 92.3%, respectively. Conclusion : Pleural fluid cell $IFN-{\gamma}$ production assay may be useful for the diagnosis of tuberculous pleurisy.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.149-161
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• 2000

Background : Residual pleural thickening (RPT) develops in about 50% of tuberculous pleurisy ($PL_{TB}$). Some reports have suggested that elevated TNF-$\alpha$ and impaired fibrinolysis could be the cause of RPT, but until now, the mechanism and predictors of RPT have not been well known. TGF-$\beta$ has been known to promote fibrogenesis and is increased in tuberculous pleural fluid (PF). $PL_{TB}$ and malignant pleurisy ($PL_{MAL}$) manifest lymphocyte-dominant exudative pleural effusion, and it has clinical implications in the differentiation of the two diseases based on the findings of pleural effusion. We performed this study to compare pleural fluid TNF-$\alpha$ TGF-$\beta$, and fibrinolytic parameters between $PL_{TB}$ and $PL_{MAL}$, and to find the predictors of RPT in $PL_{TB}$. Methods : Thirty-five $PL_{TB}$ and 14 $PL_{MAL}$ patients who were admitted to the Asan Medical Center from February 1997 to August 1999 were enrolled. All $PL_{TB}$ patients were prescribed a primary, short-course, anti-tuberculosis regimen. INF-$\alpha$ tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), plasminogen, $\alpha$2-antiplasmin, and D-dimer were measured in both PF and PB. TGF-$\beta$was measured only in PF. Clinical characteristics, TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters were compared between patients with RPT less than 2 mm and patients with more than 2 mm of the thirty patients who completed the anti-tuberculosis treatment. Results : The levels of TNF-$\alpha$ tPA, PAI-1, plasminogen, $\alpha$2-antiplasmin, and D-dimer in PF were higher than those in peripheral blood (PB) in $PL_{TB}$, whereas only plasminogen, $\alpha$2-antiplasmin, and D-dimer were higher in PF than in PB in $PL_{MAL}$. Pleural fluid TNF-$\alpha$ TGF-$\beta$, PAI-1, plasminogen, $\alpha$2-antiplasmin were increased in $PL_{TB}$ compared with $PL_{MAL}$, but these factors did not show any further advantages over ADA in differentiation between $PL_{TB}$ and $PL_{MAL}$. TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters did not show any differences between patients with RPT less than 2 mm and patients with RPT more than 2 mm. Conclusion : Our data suggest that TNF-$\alpha$, TGF-$\beta$ and fibrinolytic parameters may play some role for the development of RPT in $PL_{TB}$, but they failed to predict the occurrence of RPT in $PL_{TB}$. Also these parameters did not seem to have any advantages over ADA in differentiating between two diseases.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.44-51
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• 1997

Background : The changes of the composition in the T-lymphocyte are important as an immunological abnormality in the pathogenesis of tuberculosis. Previously, the second type of TCR dimer(${\gamma}{\delta}$ T lymphocyte) that did not express CD4 or CD8 molecules was found. In other reports the presence of this type of lymphocytes was increased in the initial stage of tuberculous infections. Method : To determine whether there are some differences in the T-lymphocyte subsets in the peripheral blood or pleural effusion between pleural tuberculosis and other pleurisy. Thirty patients with pleural effusion among the forty-nine patients were examined T-lymphocyte subset analysis(CD4+T-cell,CD8+ T-cell,${\gamma}{\delta}$ T-lymphocytes) with anti- Leu4, anti-Leu3a, anti-Lea2a, anti HLA-DR and anti-TCR-${\gamma}{\delta}$-1(Becton & Dickinson Co.). Results : The average age of the patients was 50 years old(17-81year). There were 33 males and 16 female patients. Patiensts with tuberculosis are 30cases(tuberculous pleurisy 15), lung cancer 12cases(malignant effusion 9) and pneumonia 7cases(parapneumonic effusion 6cases) In T lymphocyte subsets of pleural effusion, helper T lymphocyte(54.6 + 13.8 %) of tuberculous pleurisy was higher than that(36.2 + 25.3 %) of non-tuberculous pleurisy(p=0.04). The peripheral blood ${\gamma}{\delta}$ T-lymphocytes in tuberculousis was insignificantly higher than non-tuberculous patients(p= 0.24). The peripheral blood ${\gamma}{\delta}$ T-lymphocytes and pleural ${\gamma}{\delta}$ T-Iymphocytes in tuberculous pleurisy was insignificantly higher than in non-tuberculous pleurisy(p= 0.16, p= 0.12). Conclusion : The percentage of -${\gamma}{\delta}$ T lymphocytes among the total T-lymphocytes is not significantly increased in the peripheral blood or pleural effusion of the pleural tuberculosis. ${\gamma}{\delta}$ T lymphocytes is less useful as a diagnostic method of pleural tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.625-630
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• 2005

Background : Determining the cause of an exudative pleural effusion is sometimes quite difficult, especially between malignant and tuberculous effusions. Twenty percent of effusions remain undiagnosed even after a complete diagnostic evaluation, including pleural biopsy. The activity of tumor necrosis factor-alpha (TNF-${\alpha}$), which is the one of proinflammatory cytokines, is increased in both infectious and malignant effusions. The aim of this study was to investigate the diagnostic efficiency of TNF-${\alpha}$ activity in distinguishing tuberculous from malignant effusions. Methods : 46 patients (13 with malignant pleural effusion, 33 with tuberculous pleural effusion) with exudative pleurisy were included. TNF-${\alpha}$ concentrations were measured in the pleural fluid and serum samples using an enzyme-linked immunosorbent assay (ELISA). In addition, TNF-${\alpha}$ ratio (pleural fluid TNF-${\alpha}$ : serum TNF-${\alpha}$) was calculated. Results : TNF-${\alpha}$ concentration and TNF-${\alpha}$ ratio in the pleural fluid were significantly higher in the tuberculous effusions than in the malignant effusions (p<0.05). However, the serum levels of TNF-${\alpha}$ in the malignant and tuberculous pleural effusions were similar (p>0.05). The cut off points for the pleural fluid TNF-${\alpha}$ level and TNF-${\alpha}$ ratio were found to be 136.4 pg/mL and 6.4, respectively. The sensitivity, specificity and area under the curve were 81%, 80% and 0.82 for the pleural fluid TNF-${\alpha}$ level (p<0.005) and 76%, 70% and 0.72 for the TNF-${\alpha}$ ratio (p<0.05). Conclusion : We conclude that pleural fluid TNF-${\alpha}$ level and TNF-${\alpha}$ ratio can distinguish a malignant pleural effusion from a tuberculous effusion, and can be additional markers in a differential diagnosis of tuberculous and malignant pleural effusion. The level of TNF-${\alpha}$ in the pleural fluid could be a more efficient marker than the TNF-${\alpha}$ ratio.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.695-702
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• 1995

Background: Since polymerase chain reaction(PCR) was devised by Saiki in 1985, it has been used extensively in various fields of molecular biology. Clinically, PCR is especially useful in situation when microbiological or serological diagnosis is limited by scanty amount of causative agents. Thus, PCR can provide rapid and sensitive way of detecting M. tuberculosis in tuberculosis pleurisy which is diagnosed in only about 60 % of cases by conventional method. Method: To evaluate the diagnostic usefulness of PCR in tuberculosis pleurisy, The results of PCR was compared with those of conventional method, including pleural biopsy. The pleural effusion fluid was collected from 7 proven patients, 7 clinically suspected patients and control group(7 patients with malignant effusion). We extracted DNA from pleural fluid by modified method of Eisennach method(1991). The amplification target for PCR was 123 base pair DNA, a part of IS6110. Result: 1) Sensitivity of PCR: We detected upto 50fg DNA. 2) In patients with pleural effusion of proven tuberculosis, the positive rate of PCR was 85.7%(6/7). In patients with pleural effusion of clinically suspected tuberculosis, the positive rate was 71.5%(5/7). In control group, positive rate was 0%(0/7). Conclusion: We concluded that PCR method could be a very rapid, sensitive and specific one for diagnosis of M tuberculosis in pleural effusion. Further studies should be followed for the development of easier method.