Weekly irinotecan and carboplatin for patients with small cell lung cancer / 영남의대학술지

BACKGROUND: Lung cancer is the most common cause of cancer-related death worldwide and in Korea, and small cell lung cancer (SCLC) is the most deadly tumor type in the different lung cancer histology. Chemotherapy is the main strategy of the treatment for SCLC, and etoposide and platinum regimen has been the only standard chemotherapy for about 30 years. To test feasibility of weekly divided dose irinotecan and carboplatin for Korean patients is the aim of this study. METHODS: Patients with histologically or cytologically confirmed extensive stage SCLC were included. Patients with limited stage (LD), who could not tolerate concurrent chemoradiotherapy were also included. All the patients received irinotecan 60 mg/m2, carboplatin 2 area under the curve at day 1, 8, and 15 every 4 weeks. Study regimen was discontinued when the disease progressed or intolerable side effects occurred. No more than 6 cycles of chemotherapy were given. RESULTS: Total 47 patients were enrolled, among them 9 patients were LD. Overall response rate was 74.5% (complete response, 14.9%; partial response, 59.6%). Side effects greater than grade 3 were neutropenia (25.5%), fatigue (12.8%), thrombocytopenia (8.5%), sepsis (4.3%), and pancytopenia (2.1%). There was no treatment related death. CONCLUSION: Weekly divided irinotecan and carboplatin regimen is effective, and safe as a first line therapy for both stage of SCLC. Large scaled, controlled study is feasible.

Role of the Neutrophil-Lymphocyte Count Ratio in the Differential Diagnosis between Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia

BACKGROUND: Differential diagnosis between pulmonary tuberculosis (TB) and bacterial community-acquired pneumonia (CAP) is often challenging. The neutrophil-lymphocyte count ratio (NLR), a convenient marker of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. We investigated the usefulness of the NLR for discriminating pulmonary TB from bacterial CAP in an intermediate TB-burden country. METHODS: We retrospectively analyzed the clinical and laboratory characteristics of 206 patients suspected of having pulmonary TB or bacterial CAP from January 2009 to February 2011. The diagnostic ability of the NLR for differential diagnosis was evaluated and compared with that of C-reactive protein. RESULTS: Serum NLR levels were significantly lower in patients with pulmonary TB than in patients with bacterial CAP (3.67+/-2.12 vs. 14.64+/-9.72, P<0.001). A NLR <7 was an optimal cut-off value to discriminate patients with pulmonary TB from patients with bacterial CAP (sensitivity 91.1%, specificity 81.9%, positive predictive value 85.7%, negative predictive value 88.5%). The area under the curve for the NLR (0.95, 95% confidence interval [CI], 0.91-0.98) was significantly greater than that of C-reactive protein (0.83, 95% CI, 0.76-0.88; P=0.0015). CONCLUSIONS: The NLR obtained at the initial diagnostic stage is a useful laboratory marker to discriminate patients with pulmonary TB from patients with bacterial CAP in an intermediate TB-burden country.

Primary Extraskeletal Mesenchymal Chondrosarcoma of the Anterior Mediastinum

No abstract available.

Primary Pulmonary Myxoid Liposarcoma with Translocation t(12;16)(q13;p11) in a Young Female Patient: A Brief Case Report

Primary liposarcoma of the lung is an extremely rare disease. To date, only 14 cases have been reported in the literature. We experienced a case of myxoid liposarcoma of the lung treated by surgery. The tumor was well-defined, solid, lobulated mass measuring 3.5x2 cm, involving the bronchus of the left lower lobe. Microscopically, myxoid liposarcoma was identified. The fluorescence in situ hybridization confirmed the presence of a reciprocal translocation involving DNA damage-inducible transcript 3 (DDIT3) and fused in sarcoma (FUS) genes. The patient is still alive with no recurrence or metastasis at the time of writing this report (on 20 months postoperatively). To our knowledge, this is the first cytogenetic case report of pulmonary myxoid liposarcoma.

Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE) / 결핵및호흡기질환

BACKGROUND: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). METHODS: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. RESULTS: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). CONCLUSION: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

MDA-7/IL-24 Expression and Its Relation with Clinicopathologic Factors in Lung Adenocarcinomas of 3 cm or Less in Diameter

PURPOSE: The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin 24 (IL-24), is a novel candidate of tumor suppressor that has been found to experimentally induce apoptosis and growth inhibition in a variety of human malignant cells. However, there have been few studies about its role in lung adenocarcinoma. Even at the same stage and with similar pathologic characteristics, lung adenocarcinomas with a diameter of 3 cm or less can have a variable prognosis depending on their biologic characteristics. The purpose of this study is to define the relationship between MDA-7/IL-24 expression and the progression of small-sized lung adenocarcinomas. MATERIALS AND METHODS: We performed immunohistochemical detection of MDA-7/IL-24 in forty-seven tissue samples from primary lung adenocarcinomas of 2 cm or < or =3 cm in diameter. A statistically significant association was found between MDA-7/IL-24 expression and tumor size (p=0.03). Although this difference did not reach statistical significance, tumors with a negative MDA-7/IL-24 expression tended to more frequently show lymph node metastasis (p=0.07). There were no significant associations for other clinicopathologic characteristics. CONCLUSION: These results suggest the possible involvement of MDA-7/IL-24 in the growth and progression of small-sized lung adenocarcinoma. MDA-7/IL-24 immunoreactivity could be used to identify a subset of adenocarcinomas of the lung of 3 cm or less in diameter that have different biologic behavior.

Clinical Manifestations of 6 Cases of Septic Pulmonary Embolism at Increased Risk Recently / 고신대학교의과대학학술지

OBJECTIVES: The aim of this study was to investigate the clinico-radiologic features and microbiologic data of patients with SPE in a tertiary care hospital in Busan. METHODS: We retrospectively analyzed clinical and radiologic features of 6 cases with septic pulmonary embolism that occurred from March 2009 to March 2011 in Dong-A university medical center. RESULTS: The mean age of the study population was 58 years, and two men and four women were included. Clinical symptoms included general weakness (5 patients), febrile sensation (4 patients) and pleuritic chest pain (2 patients). Underlying conditions were chemoport infection (4 patients), dental abscess (1 patients), and cellulitis of hip (1 patient). Chest computed tomography revealed bilateral multiple nodular opacities in most patients, and cavitation, central necrosis, feeding vessels were identified. All patients received parenteral antimicrobial therapy with or without central catheter removal, drainage of the extrapulmonary infection. Causative organisms were Pseudomonas aeruginosa (2 patients), Candida albicans (1 patient), Bacillus species (1 patient), and Klebsiella pneumonia (1 patient). CONCLUSIONS: Clinical and radiologic features of septic pulmonary embolism were various and nonspecific. The diagnosis was usually suggested by the presence of a predisposing factor of septic pulmonary embolism and CT findings of bilateral multiple nodular opacities in patients with infectious signs and symptoms. Most important underlying condition was intravascular device infection.

The Current Status of Multidrug-Resistant Tuberculosis in One Tertiary Hospital in Busan, 2005~2009 / 결핵및호흡기질환

BACKGROUND: Although the prevalence of pulmonary tuberculosis has progressively decreased all over the world, drug-resistant tuberculosis is major obstacle in treating tuberculosis. This study was performed to examine the current prevalence and risk factors of drug resistant tuberculosis in a single tertiary hospital in Busan, Korea. METHODS: We enrolled 367 patients with active pulmonary tuberculosis on a retrospective basis who had undergone mycobacterium culture and drug sensitivity tests between January 2005 and December 2009. We analyzed all clinical and radiographic parameters to find predictors related to drug resistant tuberculosis. RESULTS: At least one incident of drug resistance was found in 75 (20.4%) patients. Isoniazid (18.8%) was the most frequent resistant drug, followed by rifampin (10.9%), ethambutol (7.1%), streptomycin (4.9%), and fluoroquinolone (2.7%). Resistance to second-line drugs was found in 37 (10.1%) patients. Multidrug resistance and extensively drug resistance was evident in 39 (10.6%) and 4 (1.1%) patients, respectively. Using multiple logistic regression analysis, history of previous treatment including relapse (odd ratio [OR], 11.3; 95% confidence interval [CI], 4.92~26.08; p<0.01), treatment failure (OR, 24.1; 95% CI, 5.65~102.79; p<0.01) and an age of below 46 years-old (OR, 3.8; 95% CI, 1.62~8.65; p<0.01) were found to be independent predictors of multidrug resistant tuberculosis. CONCLUSION: We found that the prevalence of drug resistant tuberculosis was considerably high. A careful consideration for possible drug resistant tuberculosis is warranted in patients with a history of previous treatment or for younger patients.

Quantification of Serum Free RNA as a Predictive Biomarker for the Response to Chemotherapy in Patients with Lung Cancer: A Pilot Study / 결핵및호흡기질환

BACKGROUND: It is well-known that cell-free nucleic acids rise in patients with many types of malignancies. Several recent experimental studies using cancer cell lines have shown that changes in cell-free RNA are predictive of the response to chemotherapy. The objective of this study was to determine whether quantification of free RNA can be used as a biomarker for clinical responses to chemotherapy in patients with lung cancer. METHODS: Thirty-two patients with lung cancer (non-small cell lung cancer, n=24; small cell lung cancer, n=8) were divided into 2 groups according to their responses to chemotherapy (response group, n=19; non-response group, n=13). Blood samples were collected before and after two cycles of chemotherapy. Real-time quantitative RT-PCR was used for transcript quantification of the glyceraldehyde-3-phosphate dehydrogenase gene. RESULTS: The pre chemotherapy values (Response group 41.36+/-1.72 vs. Non-response group 41.33+/-1.54, p=0.78) and post chemotherapy values (Response group 39.92+/-1.81 vs. Non-response group 40.41+/-1.47, p=0.40) for cell free RNA concentrations, expressed as Ct GAPDH (threshold cycle glyceraldehyde-3-phosphate dehydrogenase gene) levels, was not different between the two groups. There was no significant relationship between changes in the cell free RNA level clinical responses after chemotherapy (p=0.43). CONCLUSION: We did not find a correlation between quantification of serum cell free RNA levels and clinical responses to chemotherapy in patients with lung cancer. Further investigations are needed to determine whether the cell free RNA level is a useful predictor of responses to chemotherapy in patients with lung cancer.

Clinical Features of Pulmonary Langerhans Cell Histiocytosis in Korea / 결핵및호흡기질환

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is characterized by a proliferation of Langerhans cells and this results in granulomas that involve multiple organs of the body. Because the incidence of PLCH is very low in Korea and worldwide, collecting the clinical data of patients with PLCH nationwide is needed to determine the clinical features of Korean patients with PLCH. METHODS: The patients with PLCH confirmed by biopsy at any body site were included and the patients should have lung lesions present. A questionnaire that had items on the symptoms, lung function tests, the roentgenographic findings and the treatment was collected retrospectively at a Korean ILD Research Meeting. RESULTS: A total of 56 cases were collected. The number of males and females was 48 and 8, respectively, and their median age was 43 years (range: 18~67 years). The patients were current or ex-smokers in 79% of the cases. The most frequent symptom was coughing (39%), followed in decreasing order by dyspnea (38%), sputum (20%) and chest pain (20%). Pneumothorax was observed in 16 (29%) patients. Lung function tests showed a normal, restrictive, mixed or obstructive pattern in 26 (61%), 7 (16%), 7 (16%) and 3 patients (7%), respectively. Nodular-cystic lesion was most frequently observed in 59% of the patients on HRCT. The lung lesions were located in the middle and upper lobes in almost the cases. The median follow-up period was 90 months (range: 1~180 months) and only two patients died during this period. CONCLUSION: This study provides a national survey of the patients with PLCH during a long follow-up period.

A Case of Mediastinal Teratoma Associated with Elevated Tumor Marker in Chronic Empyema / 결핵및호흡기질환

Most mediastinal teratomas are histologically well-differentiated tumors and benign. The majority of patients with a mediastinal teratoma are asymptomatic and their tumors are usually discovered incidentally on chest radiography. On rare occasions this tumor will rupture spontaneously into the adjacent organs. A 72-year-old female patient was admitted for dyspnea and she had a multiloculated pleural effusion in the left lung field. Although repeated pleural biopsy and pleural fluid cytology did not prove the presence of malignancy, we assumed that this was a malignant effusion because it revealed consistently high levels of carcinoembryonic antigen and carbohydrate antigen 19-9, and the chest CT scan did not show typical fat or bone density in the mass. Secondary infection and an uncontrolled septic condition due to pleural empyema finally compelled the patient to undergo a surgical operation. Mature teratoma was the final diagnosis and she has done well without recurrence for 2 months.

A Case of Bronchiectasis with Elevated Serum CA 125 Level / 결핵및호흡기질환

Serum CA 125 is the most useful marker for monitoring patients with epithelial ovarian cancer. However, it can be elevated above normal level in a variety of conditions other than ovarian cancer such as endometriosis, pelvic inflammation disease, and other malignant or nonmalignant disorders, including pulmonary diseases. Recently, we experienced a case of bronchiectasis in which the serum CA 125 level was elevated, changing with the patient's condition. There was no evidence of underlying malignant disease on positron emission tomography or on gynecologic examination, including transvaginal ultrasonography. During follow-up for 14 months, we could not find any clue of malignant disease that could have been the cause of the elevated levels of serum CA 125. Elevated serum CA 125 level should be interpreted carefully according to the patient's clinical condition. In addition, our case suggests that CA 125 may be used as a surrogate marker for acute inflammatory status for chronic pulmonary diseases.

Four Cases of a Cerebral Air Embolism Complicating a Percutaneous Transthoracic Needle Biopsy

A percutaneous transthoracic needle biopsy is a common procedure in the practice of pulmonology. An air embolism is a rare but potentially fatal complication of a percutaneous transthoracic needle biopsy. We report four cases of a cerebral air embolism that developed after a percutaneous transthoracic needle biopsy. Early diagnosis and the rapid application of hyperbaric oxygen therapy is the mainstay of therapy for an embolism. Prevention is the best course and it is essential that possible risk factors be avoided.

Prognostic Significance of Fascin Expression in Stage I Non-small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Fascin is an actin-bundling protein that plays an important role in cellular motility. Fascin is normally expressed in the neuronal and mesenchymal cells and its expression is low or absent in the epithelia. However, an overexpression of fascin has been linked to the invasive behavior of some neoplasms such as breast, stomach and ovarian tumors. In this study, we evaluated the expression of fascin and its prognostic significance in stage I non-small cell lung cancer (NSCLC). METHODS: Immunohistochemical staining for fascin was performed on the paraffin-embeded tissue sections of 81 cases of resected NSCLC. Staining of more than 5% of the tumor cells was recorded as positive immunoreactivity. RESULTS: Fascin expression was seen in 73% (59/81) of the cases and this was more frequently seen in squamous cell carcinoma than in adenocarcinoma (93% vs 42%). There were no significant correlations of fascin immunoreactivity with tumor recurrence and overall survival. CONCLUSION: The expression rate of fascin was relatively high in NSCLC, but this was without prognostic significance. The exact clinical role of fascin should be defined through further investigations.

A Case of Bronchiectasis with High Serum CA19-9 / 결핵및호흡기질환

An elevated serum CA19-9 level is an indication of pancreatic and biliary tract cancer. However, it has recently become known that nonmalignant gastrointestinal diseases and a variety of nonmalignant respiratory diseases, such as idiopathic interstial pneumonia, collagen vascular disease associated lung diseases, diffuse panbronchiolitis and bronchiectasis, can also show an elevated serum CA19-9 level. We recently encountered a case of bronchiectasis with persistently elevated serum CA19-9, but without any evidence of malignant disease in endoscopic retrograde pancreatocholangiography, abdominal computed tomography, and positron emission tomography. After serial follow-up of 3 years and 10 months, there was still no evidence of cancer. It is believed that the elevated serum CA19-9 level was due to bronchiectasis. An elevated serum CA19-9 level should be interpreted carefully with the patients' clinical condition.

Eosinophilic Pneumonia / 결핵및호흡기질환

No abstract available.

Diagnosis of Malignant Pleural Effusion by using Aberrant Methylation of p16 and RARB2 / 결핵및호흡기질환

BACKGROUND: A diagnosis of malignant pleural effusion is clinically important, as the prognosis of lung cancer patients with malignant pleural effusion is poor. The diagnosis will be difficult if a cytological test is negative. This study was performed to investigate whether the detection of hypermethylation of the p16 (CDKN2A) and retinoic acid receptor b2 (RARB2) genes in pleural fluid is useful for a diagnosis of malignant pleural effusion. METHODS: Pleural effusion was collected from 43 patients and was investigated for the aberrant promoter methylation of the RARB2 and CDKN2A genes by use of methylation-specific PCR. Results were compared with findings from a pleural biopsy and from pleural fluid cytology. RESULTS: Of 43 cases, 17 cases of pleural effusion were due to benign diseases, and 26 cases were from lung cancer patients with malignant pleural effusion. Hypermethylation of the RARB2 and CDKN2A genes was not detected in the case of benign diseases, independent of whether or not the patients had ever smoked. In 26 cases of malignant pleural effusion, hypermethylation of RARB2, CDKN2A or either of these genes was detected in 14, 5 and 15 cases, respectively. The sensitivities of a pleural biopsy, pleural fluid cytology, hypermethylation of RARB2, hypermethylation of CDKN2A, or hypermethylation of either of the genes were 73.1%, 53.8%, 53.8%, 19.2%, and 57.7%, respectively; negative predictive values were 70.8%, 58.6%, 58.6%, 44.7%, and 60.7%, respectively. If both genes are considered together, the sensitivity and negative predictive value was lower than that for a pleural biopsy, but higher than that for pleural fluid cytology. The sensitivity of hypermethylation of the RARB2 gene for malignant pleural effusion was lower in small cell lung cancers than in non-small cell lung cancers. CONCLUSION: These results demonstrate that detection of hypermethylation of the RARB2 and CDKN2A genes showed a high specificity, and sensitivity was higher than for pleural fluid cytology. With a better understanding of the pathogenesis of lung cancer according to histological types at the molecular level, and if appropriate genes are selected for hypermethylation testing, more precise results may be obtained.