• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.785-795
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• 1997

Background : Tumor markers have been used in diagnosis, predicting the extent of disease, monitoring recurrence after therapy and prediction of prognosis. But the utility of markers in lung cancer has been limited by low sensitivity and specificity. TPA-M is recently developed marker using combined monoclonal antibody of Cytokeratin 8, 18, and 19. This study was conducted to evaluate the efficacy of new tumor marker, TPA-M by comparing the estabilished markers SCC, CEA, Cyfra21-1 in lung cancer. Method : An immunoradiometric assay of serum CEA, sec, Cyfra21-1, and TPA-M was performed in 49 pathologically confirmed lung cancer patients who visited Keimyung University Hospital from April 1996 to August 1996, and 29 benign lung diseases. Commercially available kits, Ab bead CEA (Eiken) to CEA, SCC RIA BEAD (DAINABOT) to SCC, CA2H (TFB) to Cyfra2H. and TPA-M (DAIICHI) to TPA-M were used for this study. Results : The mean serum values of lung cancer group and control group were $10.05{\pm}38.39{\mu}/L$, $1.59{\pm}0.94{\mu}/L$ in CEA, $3.04{\pm}5.79{\mu}/L$, $1.58{\pm}2.85{\mu}/L$ in SCC, $8.27{\pm}11.96{\mu}/L$, $1.77{\pm}2.72{\mu}/L$ in Cyfra21-1, and $132.02{\pm}209.35\;U/L$, $45.86{\pm}75.86\;U/L$ in TPA-M respectively. Serum values of Cyfra21-1 and TPA-M in lung cancer group were higher than control group (p<0.05). Using cutoff value recommended by the manufactures, that is $2.5{\mu}/L$ in CEA, $3.0{\mu}/L$ in Cyfra21-1, 70.0 U/L in TPA-M, and $2.0{\mu}/L$ in SCC, sensitivity and specificity of lung cancer were 33.3%, 78.6% in CEA, 50.0%, 89.7% in Cyfra21-1, 52.3%, 89.7% in TPA-M, 23.8%, 89.3% in SCC. Sensitivity and specificity of nonsmall cell lung cancer were 36.1%, 78.1% in CEA, 50.1%, 89.7% in Cyfra21-1, 53.1%, 89.7% in TPA-M, 33.8%, 89.3% in SCC. Sensitivity and specificity of small cell lung cancer were 25.0%, 78.5% in CEA, 50.0%, 89.6% in Cyfra21-1, 50.0%, 89.6% in TPA-M, 0%, 89.2% in SCC. Cutoff value according to ROC(Receiver operating characteristics) curve was $1.25{\mu}/L$ in CEA, $1.5{\mu}/L$ in Cyfra2-1, 35 U/L in TPA-M, $0.6{\mu}/L$ in SCC. With this cutoff value, sensitivity, specificity, accuracy and kappa index of Cyfra21-1 and TPA-M were better than CEA and SCC. SCC only was related with statistic significance to TNM stages, dividing to operable stages(TNM stage I to IIIA) and inoperable stages (IIIB and IV) (p<0.05). But no tumor markers showed any correlation with significance with tumor size(p>0.05). Conclusion : Serum TPA-M and Cyfra21-1 shows higher sensitivity and specificity than CEA and SCC in overall lung cancer and nonsmall cell lung cancer those were confirmed pathologically. SCC has higher specificity in nonsmall cell lung cancer. And the level of serum sec are signiticantly related with TNM staging.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.56-78
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• 1998

Objective: Chronic hepatitis B infection (CHB) occurs in 6% to 10% of population in Korea. In ethinic communities where prevalence of chronic infection is high such as Korea, transmission of hepatitis B infection is either vertical (ie, by perinatal infection) or by close family contact (usually from mothers or siblings) during the first 5 years of life. The development of chronic hepatitis B infection is increasingly more common the earlier a person is exposed to the virus, particularly in fetal and neonatal life. And it progress to cirrhosis and hepatocellular carcinoma, especially in severe liver damage and perinatal infection. Histopathology of CHB is important when evaluating the final outcomes. A numerical scoring system which is a semiquantitatively assessed objective reproducible classification of chronic viral hepatitis, is a valuable tool for statistical analysis when predicting the outcome and evaluating antiviral and other therapies. In this study, a numerical scoring system (Ludwig system) was applied and compared with the conventional histological classification of De Groute. And the comparative analysis of cinical findings, family history, serology, and liver function test by histopathological findings in chronic hepatitis B of children was done. Methods: Ninety nine patients [mean age=9 years (range=17 months to 16 years)] with clinical, biochemical, serological and histological patterns of chronic HBV infection included in this study. Five of these children had hepatocelluar carcinoma. They were 83 male and 16 female children. They all underwent liver biopsies and histologic evaluation was performed by one pathologist. The biopsy specimens were classified, according to the standard criteria of De Groute as follows: normal, chronic lobular hepatitis (CLH), chronic persistent hepatitis (CPH), mild to severe chronic active hepatitis (CAH), or active cirrhosis, inactive cirrhosis, hepatocellular carcinoma (HCC). And the biopsy specimens were also assessed and scored semiquantitatively by the numerical scoring Ludwig system. Serum HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc (IgG, IgM), and HDV were measured by radioimunoassays. Results: Male predominated in a proportion of 5.2:1 for all patients. Of 99 patients, 2 cases had normal, 2 cases had CLH, 22 cases had CPH, 40 cases had mild CAH, 19 cases had moderate CAH, 1 case had severe CAH, 7 cases had active cirrhosis, 1 case had inactive cirrhosis, and 5 cases had HCC. The mean age, sex distribution, symptoms, signs, and family history did not differ statistically among the different histologic groups. The numerical scoring system was correlated well with the conventional histological classification. The histological activity evaluated by both the conventional classification and the scoring system was more severe as the levels of serum aminotransferases were higher. In contrast, the levels of serum aminotransferases were not useful for predicting the degree of histologic activity because of its wide range overlapping. When the histological activity was more severe and especially the cirrhosis more progressing, the prothrombin time was more prolonged. The histological severity was inversely related with the duration of seroconversion of HBeAg. Conclusions: The histological activity could not be accurately predicted by clinical and biochemical findings, but by the proper histological classification of the numerical scoring system for the biopsy specimen. The numerical scoring system was correlated well with the conventional histological classification, and it seems to be a valuable tool for the statistical analysis when predicting the outcome and evaluating effects of antiviral and other therapies in chronic hepatitis B in children.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.351-360
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• 1995

Background: Pressure support(PS) is becomimg a widely accepted method of mechanical ventilation either for total unloading or for partial unloading of respiratory muscle. The aim of the study was to find out if PS exert different effects on respiratory mechanics in synchronized intermittent mandatory ventilation(SIMV) and continuous positive airway pressure (CPAP) modes. Methods: 5, 10 and 15 cm $H_2O$ of PS were sequentially applied in 14 patients($69{\pm}12$ yrs, M:F=9:5) and respiratory rate (RR), tidal volume($V_T$), work of breathing(WOB), pressure time product(PTP), $P_{0.1}$, and $T_1/T_{TOT}$ were measured using the CP-100 pulmonary monitor(Bicore, USA) in SIMV and CPAP modes respectively. Results: 1) Common effects of PS on respiratory mechanics in both CPAP and SIMV modes As the level of PS was increased(0, 5, 10, 15 cm $H_2O$), $V_T$ was increased in CPAP mode($0.28{\pm}0.09$, $0.29{\pm}0.09$, $0.31{\pm}0.11$, $0.34{\pm}0.12\;L$, respectively, p=0.001), and also in SIMV mode($0.31{\pm}0.15$, $0.32{\pm}0.09$, $0.34{\pm}0.16$, $0.36{\pm}0.15\;L$, respectively, p=0.0215). WOB was decreased in CPAP mode($1.40{\pm}1.02$, $1.01{\pm}0.80$, $0.80{\pm}0.85$, $0.68{\pm}0.76$ joule/L, respectively, p=0.0001), and in SIMV mode($0.97{\pm}0.77$, $0.76{\pm}0.64$, $0.57{\pm}0.55$, $0.49{\pm}0.49$ joule/L, respectively, p=0.0001). PTP was also decreased in CPAP mode($300{\pm}216$, $217{\pm}165$, $179{\pm}187$, $122{\pm}114cm$ $H_2O{\cdot}sec/min$, respectively, p=0.0001), and in SIMV mode($218{\pm}181$, $178{\pm}157$, $130{\pm}147$, $108{\pm}129cm$ $H_2O{\cdot}sec/min$, respectively, p=0.0017). 2) Different effects of PS on respiratory mechanics in CP AP and SIMV modes By application of PS (0, 5, 10, 15 cm $H_2O$), RR was not changed in CPAP mode($27.9{\pm}6.7$, $30.0{\pm}6.6$, $26.1{\pm}9.1$, $27.5{\pm}5.7/min$, respectively, p=0.505), but it was decreased in SIMV mode ($27.4{\pm}5.1$, $27.8{\pm}6.5$, $27.6{\pm}6.2$, $25.1{\pm}5.4/min$, respectively, p=0.0001). $P_{0.1}$ was reduced in CPAP mode($6.2{\pm}3.5$, $4.8{\pm}2.8$, $4.8{\pm}3.8$, $3.9{\pm}2.5\;cm$ $H_2O$, respectively, p=0.0061), but not in SIMV mode($4.3{\pm}2.1$, $4.0{\pm}1.8$, $3.5{\pm}1.6$, $3.5{\pm}1.9\;cm$ $H_2O$, respectively, p=0.054). $T_1/T_{TOT}$ was decreased in CPAP mode($0.40{\pm}0.05$, $0.39{\pm}0.04$, $0.37{\pm}0.04$, $0.35{\pm}0.04$, respectively, p=0.0004), but not in SIMV mode($0.40{\pm}0.08$, $0.35{\pm}0.07$, $0.38{\pm}0.10$, $0.37{\pm}0.10$, respectively, p=0.287). 3) Comparison of respiratory mechanics between CPAP+PS and SIMV alone at same tidal volume. The tidal volume in CPAP+PS 10 cm $H_2O$ was comparable to that of SIMV alone. Under this condition, the RR($26.1{\pm}9.1$, $27.4{\pm}5.1/min$, respectively, p=0.516), WOB($0.80{\pm}0.85$, 0.97+0.77 joule/L, respectively, p=0.485), $P_{0.1}$($3.9{\pm}2.5$, $4.3{\pm}2.1\;cm$ $H_2O$, respectively, p=0.481) were not different between the two methods, but PTP($179{\pm}187$, $218{\pm}181 cmH_2O{\cdot}sec/min$, respectively, p=0.042) and $T_1/T_{TOT}$($0.37{\pm}0.04$, $0.40{\pm}0.08$, respectively, p=0.026) were significantly lower in CPAP+PS than in SIMV alone. Conclusion: PS up to 15 cm $H_2O$ increased tidal volume, decreased work of breathing and pressure time product in both SIMV and CPAP modes. PS decreased respiration rate in SIMV mode but not in CPAP mode, while it reduced central respiratory drive($P_{0.1}$) and shortened duty cycle ($T_1/T_{TOT}$) in CPAP mode but not in SIMV mode. By 10 em $H_2O$ of PS in CPAP mode, same tidal volume was obtained as in SIMV mode, and both methods were comparable in respect to RR, WOB, $P_{0.1}$, but CPAP+PS was superior in respect to the efficiency of the respiratory muscle work (PTP) and duty cycle($T_1/T_{TOT}$).

• Radiation Oncology Journal
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• v.17 no.2
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• pp.100-107
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• 1999

Purpose: This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Materials and Methods Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45~67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in T2, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal Iymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intravenous cis-Platin (100 mg/m$^{2}$) on day 1 and oral Etoposide (50 mg/m$^{2}$/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Results : Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred In 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/l3) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor stagings were pT0 in 3 patients, pTl in 6, and pT2 in 3. Lymph node status findings were pN0 in 8 patients, pN1 in 1, and pN2 in 3. Pathologic tumor down-staging was 61.5% (8/13) including complete response in three patients ($23.7%). Tumor stage was unchanged in four patients (30.8%) and progression was in one (7.7%). Conclusions : Pre-operative concurrent chemoradiotherapy for Stage IIIA (N2) non-small cell lung cancer demonstrated satisfactory results with no increased severe acute complications. This treatment shceme deserves more patinet accrual with long-term follow-up.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.846-854
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• 1995

Background: Cytokeratin 19 is a subunit of cytokeratin intermediate filament expressed in simple epithelia such as respiratory epithelial cells and their malignant counterparts. An immunoradiometric assay is available to detect a fragment of the cytokeratin, referred to as Cyfra 21-1 in the serum. This study was conducted to evaluate the clinical utility of this new marker in the diagnosis of lung cancer compared with established markers of squamous cell carcinoma antigen (SCC Ag) and carcino-embryonic antigen(CEA). In addition, we compared the diagnostic sensitivity and specificity of Cyfra 21-1 with those of SCC Ag in squamous cell carcinoma of the lung. We also measured the level of Cyfra 21-1 in the different stages of squamous cell carcinoma of the lung. Method: We measured Cyfra 21-1(ELSA-CYFRA 21-1), SCC Ag(ABBOTT SCC RIABEAD) and CEA(ELSA2-CEA) in 79 patients with primary lung cancer and in 78 persons as a comparison group including 32 patients with pulmonary tuberculosis, 23 patients with benign lung disease and 23 cases with healthy individual. Cyfra 21-1 is measured by a solid-phase immunoradiometric assay(CIS Bio International, France) based on the two-site sandwich method. SCC Ag is measured by a radioimmunoassay(Abbott Laboratories, USA). CEA is measured by a immunoradiometric assay(CIS Bio International, France). All data were expressed as the mean$\pm$standard deviation. Results: 1) The mean value of Cyfra 21-1 was $18.38{\pm}3.65\;ng/mL$ in the lung cancer and $1.l6{\pm}0.53\;ng/mL$ in the comparison group(p<0.0001). SCC Ag was $3.53{\pm}6.06\;ng/mL$ in the lung cancer and $1.19{\pm}0.5\;ng/mL$ in the comparison group(p<0.01). CEA was $35.03{\pm}13.9\;ng/mL$ in the lung cancer and $2.89{\pm}1.01\;ng/mL$ in the comparison group(p<0.0001). 2) Cyfra 21-1 level in squamous cell carcinoma($31.52{\pm}40.13\;ng/mL$) was higher than that in adenocarcinoma($2.41{\pm}1.34\;ng/mL$)(p<0.0001) and small cell carcinoma($2.15{\pm}2.05\;ng/mL$)(p=0.007). SCC Ag level in squamous cell carcinoma($5.1{\pm}7.68\;ng/mL$) was higher than that in adenocarcinoma($1.36{\pm}0.69\;ng/mL$)(p=0.009) and small cell carcinoma($1.1{\pm}0.24\;ng/mL$) (p=0.024). 3) The level of Cyfra 21-1 was not correlated with the progression of stage in squamous cell carcinoma of the lung. 4) Using the cut-off value of 3.3ng/mL, the diagnostic sensitivity of Cyfra 21-1 was 83% in squamous cell carcinoma, 22% in adenocarcinoma and 17% in small cell carcinoma. The sensitivity of SCC Ag and CEA were 39% and 20%, respectively in squamous cell carcinoma, 11% and 39% in adenocarcinoma, and 0% and 33% in small cell carcinoma. 5) Comparison of the receiver operating characteristics curves(ROC curve) for Cyfra 21-1, SCC Ag and CEA revealed that Cyfra 21-1 showed highest diagnostic sensitivity among them in the diagnosis of lung cancer. Conclusion: Cyfra 21-1 is thought to be a better tumor marker for the diagnosis of lung cancer than SCC Ag and CEA, especially in squamous cell carcinoma of the lung.