Efficacy of Darbepoetin alfa in Anemia Developed during Chemotherapy for Lung Cancer / 결핵및호흡기질환

BACKGROUND: Anemia is quite common in lung cancer patients and known to decrease the quality of life. Darbepoetin alfa is an erythropoiesis-stimulating protein approved for administration to cancer patients. This study examined the efficacy and safety of darbepoetin alfa in lung cancer patients with a hemoglobin concentration 10 g/dl. The efficacy and safety were measured by comparing the hemoglobin concentration and assessing the adverse events. RESULTS: After chemotherapy, the hemoglobin concentration decreased to 9.03+/-0.64 g/dl. With the darbepoetin alfa treatment, the hemoglobin concentration increased to 10.09+/-1.17 g/dl after 4 weeks reaching a peak hemoglobin concentration of 10.45+/-1.18 g/dl. The changes in hemoglobin after 4 and 8 weeks with treatment were 1.08+/-1.24 g/dl and 1.38+/-1.59 g/dl (p<0.01). At least a 1 g/dl or more increase in hemoglobin was observed in 62.4% of patients. There were no serious adverse effects except for some mild reactions. CONCLUSION: Darbepoetin alfa administered to lung cancer patients appears to be an effective, well-tolerated treatment for chemotherapy induced anemia.

Tracheopathia Osteochondroplastica with Recurrent Massive Hemoptysis and Atelectasis: A Case Report / 결핵및호흡기질환

We treated a rare case of TO that presented with recurrent massive hemoptysis that resulted in total obstruction of the bronchus intermedius by very large blood clots. Bronchoscopic intervention resulted in a full recovery from the atelectasis. However, there are no guidelines for preventing recurrence of the hemoptysis or disease progression. Conservative and expectant management are used to treat these patients and most do well.

A Case of Wegener's Granulomatosis that Presented as a Single Lung Mass / 결핵및호흡기질환

Wegener's granulomatosis is a disease with an unknown etiology that is characterized by necrotizing granulomatous vasculitis involving the upper and lower respiratory tract and the kidneys. The typical pulmonary findings are bilaterally involved multiple variable sized nodules. We report a case of Wegener's granulomatosis that presented as a single lung mass. A male patient presented with a nasal obstruction, arthralgia, cough, and intermittent dyspnea. The chest radiograph showed a mass, approximately 4.5 cm in diameter, in the right lower lobe. Lung cancer or tuberculosis was initially considered. However, the clinical, laboratory and pathological findings of the mass indicated Wegener's granulomatosis. The patient was administered prednisolone and cyclophosphamide, and improved temporarily. Unfortunately, the immunocompromised patient expired as a result of respiratory failure with pneumonia.

Promoter Polymorphism of RRM1 Gene in Korean Lung Cancer Population / 결핵및호흡기질환

BACKGROUND: LOH11A is a region with frequent allele loss (>75%) in lung cancer that is located on the centromeric part of chromosome 11p15.5. Clinical and cell biological studies suggest that this region contains a gene associated with metastatic tumor spread. RRM1 encoding the M1 subunit of ribonucleotide reductase, which is an enzyme that catalyses the rate-limiting step in deoxyribonucleotide synthesis, is located in the LOH11A region. METHODS: Polymorphisms were found at nucleotide position (-)37 (C/A) and (-)524 (C/T) from the beginning of exon 1 of the RRM1 gene that might regulate the expression of RRM1. We studied the polymorphisms in 127 Korean individuals (66 lung cancer and 61 normal controls) and compared with those of 140 American patients with lung cancer. RESULTS: CC, AC and AA were found at the (-)37 position in 64(50.4%), 55(43.3%), and 8(6.3%) out of 127 Korean individuals (66 cancer, 61 non-cancer patients), respectively. There was a similar frequency of allele A at (-)37 in the American(27.9%) and Korean population(28.0%). CC, CT and TT was found at the (-)524 position in 24(18.9%), 44(34.6%), and 59(46.5%) out of the 127 Korean individuals, respectively. There was a similar frequency of allele C at (-)524 in the American(34.6%) and Korean population(36.2%).There was no difference in the frequency of the (-)37 and (-)524 genotypes between the cancer and non-cancer group. However there was a significant correlation of the genotypes between (-)37 and (-)524 (p<0.001), which suggests the possible coordination of these polymorphisms in the regulation of the promoter activity of the RRM1 gene. CONCLUSION: RRM1 promoter polymorphisms were not found to be significant risk factors for lung cancer. However, a further study of the promoter activity and expression of the RRM1 gene according to the pattern of the polymorphism will be needed.

Clinical Response to Etoposide Plus Carboplatin and Topotecan Chemotherapy in Small Cell Lung Cancer / 결핵

BACKGROUND: This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. METHODS: One hundred and ten patients with previously untreated SCLC received etoposide(100mg/m2 i.v., day 1 to 3) and carboplatin(300mg/m2 i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan(1.5mg/m2) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). RESULTS: One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). CONCLUSION: The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

Pulmonary Oxalosis Caused by Aspergillus Niger Infection / 결핵

The Aspergillus species produces metabolic products that play a significant role in the destructive processes in the lung. We experie nced a case of chronic necrotizing pulmonary aspergillosis caused by an Aspergillus niger infection, which contained numerous calcium oxalate crystals in the necrotic lung tissue. A 46-year-old man, who had a history of pulmonary tuberculosis, presented with high fever, intermittent hemoptysis and pulmonary infiltrations with a cavity indicated by the chest radiograph. Despite being treated with several antibiotics and anti-tuberculosis regimens, the high fever continued. The sputum cultures yielded A. niger repeatedly, and intravenous amphotericin B was then introduced. The pathological specimen obtained by a transbron chial lung biopsy revealed numerous calcium oxalate crystals in a background of acute inflam matory exudates with no identification of the organism. Intravenous amphotericin B was con tinued at a total dose of 1600 mg, and at that time he was afebrile, although the intermittent hemoptysis continued. On the 63rd hospital day, a massive hemoptysis (about 800 mL) developed, which could not be controlled despite embolizing the left bronchial artery. He died of respiratory failure the next day. It is believed that the oxalic acid produced by A. niger was the main cause of the patient's pulmonary injury and the ensuing massive hemoptysis.

Utility of FDG-PET in Solitary Pulmonary Nodules and the Relationship Between Standardized Uptake Values of PET and Serum Glucose / 결핵

BACKGROUND: The solitary pulmonary nodule(SPN) presents a diagnostic dilemma to the physician and the patients in the our nation with high incidence of tuberculoma. We could not exclude whether the SPN was benign or malignant by the change of the size at chest radiograph and findings of chest CT. Recently, positron emission tomography(PET) have been tried as the differential diagnostic method of SPN. We evaluated the efficacy of PET for differentiating malignant from benign SPN and the relationship between standardized uptake values(SUV) of PET and serum glucose. METHODS: Between January 2001 and July 2002, sixty-one patients with pulmonary nodule were examined by the chest CT and PET. The SPN has been finally diagnosed by the transthorasic needle aspiration and biopsy, bronchoscopic biopsy, and open lung biopsy. RESULTS: Forty eight patients had a malignant nodule(23 squamous cell lung carcinoma, 16 adenocarcinoma, 9 small cell lung cancer) and thirteen patients had a benign nodule(3 tuberculoma, 9 inflammatory granuloma, 1 cryptococcosis). The mean size of malignant and benign nodule was 40.6 mm and 20.0 mm, respectively. All malignant nodules showed a marked increase in 18 fluorodeoxyglucose (FDG) uptake. Mean SUV of malignant was 9.52+/-5.20 and benign nodule was 1.61+/-3.60. There were false positive cases with an increase in 18-FDG uptake (2 tuberculoma, 1 inflammatory granuloma). The SUV of malignant nodule in diabetes patients has no difference in non diabetes patients(9.10+/-4.51 vs 9.65+/-5.46). The sensitivity and specificity of the PET scan for SPN were 100%, 77%, respectively. The positive and negative predictive values were 94% and 100%. CONCLUSION: PET scanning showed highly accurate result in differentiating the malignant and benign SPN. There were no significant differences between the SUV and serum glucose in the patients with lung cancer.

Genetic Polymorphism of Epoxide Hydrolase and GSTM1 in Lung Cancer Susceptibility of Korean Population / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although 80~90% of patients with lung cancer are smokers, only 11% of smokers develop lung cancer. Genetic susceptibility according to the polymorphism of the epoxide hydrolase (mEPHX) gene and homozygous deletion of GSTM1 (M1 subunit of Glutathione S transferase) was studied in this case control study. MATERIALS AND METHODS: Genomic DNA from 76 subjects with lung cancer (40 squamous cell carcinoma, 13 adenocarcinoma, 10 subtype undetermined non-small cell lung cancer, and 13 small cell lung carcinoma) and 62 age- matched controls were extracted from peripheral white blood cells. PCR and RFLP (restriction fragments length polymorphism) with restriction enzyme (RsaI) and automatic sequencing were used for mEPHX genotyping (T-->C, Tyr113His) in exon 3 and (A-->G, His139Arg) in exon 4. Looking for homozygous deletions of GSTM1, multiplex PCR with primers for the GSTM1 gene and coagulation factor V gene (as positive control) were performed. RESULTS: The age distribution between the cancer and control groups were similar (63.6 7.2 vs. 61.1 7.9 years). The lung cancer group, however, had more smokers (73.3%, 44/60) than the control group (21/54, 38.9%, p<0.001). The rate of homozygous deletion of the GSTM1 gene was significantly higher in the lung cancer group (65.8%, 50/76) than in the control group (46.8%, 29/62, p<0.05), causing the relative risk of GSTM1 deletion for lung cancer as 2.19 (95% CI: 1.10~4.35, p=0.02). Among 118 subjects whose mEPHX gene polymorphisms were studied, 62 (52.5%) subjects showed genotypes with slow enzyme activity while 45 (38.1%) showed normal enzyme activity and 11 (9.3%) showed fast enzyme activity. There was no significant difference in the distribution of mEPHX gene polymorphisms between the two groups. CONCLUSION: The homozygous deletion of the GSTM1 gene was associated with high lung cancer susceptibility, whereas the mEPHX genotype showed no significant connection with risk of lung cancer in a sample Korean population.

Clinical Response of Docetaxel Plus Cisplatin and Paclitaxel Plus Carboplatin Chemotherpy in Non-Small Cell Lung Cancer

PURPOSE: Almost 80% of primary lung cancers are non-small cell lung cancer (NSCLC), and their prognosis is very poor since only one-fourth of patients with NSCLC present with a resectable disease at the time of diagnosis. During the last 10 years, the role of chemotherapy for NSCLC has been expanding as an adjunctive to radiation and surgery, as well as to palliative therapy for stage IV NSCLC. This study is a retrospective analysis of two chemotherapeutic regimens for the treatment of advanced NSCLC. MATERIALS AND METHODS: Between January 1999 and December 2001, 109 patients with histologically proven NSCLC (> or = stage IIIA), who received either the DP (Docetaxel 75 mg/m2 +Cisplatin 75 mg/m2, n=63, 57.8%) or the TC (Paclitaxel 175 mg/m2+ Carboplatin 5* AUC mg, n=46, 42.2%) combination chemotherapies were included. RESULTS: The patients ages ranged from 46 to 77 years, and the patients in the DP group (56.3+/-8.6 years) were younger than those in the TC group (62.1+/-8.8 years) (p0.05). Grade 3~4 peripheral neuropathy occurred in 5 patients (7.9%) in the DP group and in 8 (17.4%) in the TC group (p>0.05). CONCLUSION: The combination chemotherapies of docetaxel plus cisplatin and paclitaxel plus carboplatin are active against advanced stage NSCLC, with acceptable toxicities. As there are differences in the baseline characteristics between the two groups, no differences in survivals or response rates could be concluded.

Genetic Polymorphism of Epoxide Hydrolase and GSTM1 in Chronic Obstructive Pulmonary Disease / 결핵

BACKGROUND: Although smoking is a major cause of chronic obstructive pulmonary disease (COPD), only 10-20% of cigarette smokers develop symptomatic COPD, which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in the activities of the enzyme that detoxify hazardous chemical products, such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase M1 subunit (GSTM1) genes. METHODS: The genotypes of 58 patients with COPD, and 79 age matched control subjects, were determined by a polymerase chain reaction, followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX, and multiplex PCR for the GSTM1. RESULTS: GSTM1 was deleted in 53.3% of the subjects. There was no difference in GSTM1 deletion rates between the COPD patients (32/58, 55.2%) and the control subjects (41/79, 51.9%). The combination patterns of two polymorphisms of mEPHX showed slow enzyme activity in 29(21.2%), normal in 73(53.3%) and fast in 32(23.4%). The COPD group (7/57, 12.3%) showed a significantly lower incidence of slow enzyme activity compared to the control subjects (22/77, 28.6%, p<0.05). However, when the COPD and control groups were compared with smokers only, there were no significant differences in the genotypes of GSTM1 and mEPHX. CONCLUSION: The genotypes of GSTM1 and mEPHX were not significant risk factors of COPD in this cohort of study.

K-ras Gene Mutation in Non-Small Cell Lung Cancer

PURPOSE: Point mutation of the K-ras gene causes irreversible binding of GTP to the P21-ras protein, which induces nuclear transcription factors and enhances cellular proliferation. Point mutation of the K-ras gene is known to be a poor prognostic marker of an adenocarcinoma of the lung. As about 30% of adenocarcinomas harbor the K-ras mutation, studies are being undertaken trying to use the K-ras mutation as a marker for the early detection of lung cancer. In Korea, squamous cell carcinomas are more prevalent than adenocarcinomas, but the incidence of the K-ras mutation has not been properly investigated. MATERIALS AND METHODS: Using 25 surgically resected lung cancer specimens (10 squamous cell lung carcinomas, 10 adenocarcinomas and 5 non-small cell lung cancers), 25 pairs of DNA were extracted from cancerous and normal lung tissues. After PCR, with two sets of primers flanking codons 12~13 and 61 of the K-ras gene, the mutation was screened using single strand conformational polymorphism (SSCP). To verify the SSCP findings, automatic sequencing was also performed for all DNA's from the tumor and normal lung tissues. RESULTS: No samples with a band shift in SSCP were observed. In the sequencing of the 25 pairs of DNA, there were no mutations in codons 12, 13 or 61 of the K-ras gene. CONCLUSION: As there were no mutations in the K-ras codons 12, 13 and 61 in this study, the incidence of the K-ras mutation, in Korean lung cancer, may well be very low. However, further investigations on a larger population will be required, as we only studied 25 non-small cell lung cancer specimens, with only 10 adenocarcinomas.

Transient Cortical Blindness: A Rare Complication of Bronchial Artery Embolization / 결핵

Bronchial artery embolization (BAE) is a well accepted and effective treatment for massive and recurrent hemoptysis. However, several complications of BAE have been reported. Cortical blindness is defined as a loss of vision caused by bilateral occipital lobe lesions with normal pupillary light reflexes and a normal fundus. The reported incidence of transient cortical blindness (TCB) after cerebrovertebral angiography is approximately 1%. Two cases of TCB after BAE were found from a Medline search. Here, we report another case of TCB who was treated with BAE for a massive hemoptysis.

Transient Cortical Blindness: A Rare Complication of Bronchial Artery Embolization / 결핵

Bronchial artery embolization (BAE) is a well accepted and effective treatment for massive and recurrent hemoptysis. However, several complications of BAE have been reported. Cortical blindness is defined as a loss of vision caused by bilateral occipital lobe lesions with normal pupillary light reflexes and a normal fundus. The reported incidence of transient cortical blindness (TCB) after cerebrovertebral angiography is approximately 1%. Two cases of TCB after BAE were found from a Medline search. Here, we report another case of TCB who was treated with BAE for a massive hemoptysis.

A Case of Bronchial Glomus Tumor / 결핵

An 18-year-old female was admitted because of dyspnea at rest. A chest computed tomography (CT) scan and fiberoptic bronchoscopy demonstrated a polypoid tumor in the left main bronchus, 0.5cm distal from the carina. Surgical resection of the tumor was performed, along with. A pathological evaluation and the immunohistochemical findings led to the diagnosis of a glomus tumor, which originated from the bronchus, an area where this type of tumor has rarely been reported.