• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.448-463
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• 2000

Background : Pulmonary infiltrate is a frequent cause of morbidity and mortality in patients with leukemia. It is often hard to obtain a reliable diagnosis by clinical and radiologic findings alone. The aim of this study was to evaluate diagnostic and therapeutic benefits of invasive procedures for new lung infiltrates in leukemia. Methods : Patients with leukemia who developed new lung infiltrates from December 1994 to March 1999 were included in this study. These patients were classified into the empirical group who received empirical therapy only and into the invasive group who underwent bronchoscopy or surgical lung biopsy for the diagnostic purpose of new lung infiltrates. A retrospective chart review was done to find the etiologies of new lung infiltrates, the yield of invasive procedures, outcome as well as predicting factors for survival. Results : 1) One hundred-two episodes of new lung infiltrates developed in 90 patients with leukemia. Invasive procedures were performed in 44 episodes while 58 episodes were treated with empirical therapy only. 2) Invasive procedures yielded a specific diagnosis in 72.7%(32/44), of which 78.1% had infectious etiology. Therapeutic plan was changed in 52.3%(23/44) of patients after invasive procedures. None of them showed procedure-related mortality. 3) The overall survival rate was 62.7%(64/102). Survival rate in the invasive group (79.5%) was significantly better than that in the empirical group (50.0%) (p=0.002). 4) Upon multivariate analysis, the performance of invasive procedures, no need for mechanical ventilation and achievement of complete remission of leukemia after induction chemotherapy were the independent predicting factors for survival in patients with leukemia and new lung infiltrates. Conclusion : Bronchoscopy and surgical lung biopsy are useful in the diagnosis of new lung infiltrates in patients with leukemia. However, survival benefits of invasive procedures should be considered together with disease status of leukemia and severity of respiratory compromise.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.