Epidermal growth factor receptor mutation and pattern of brain metastasis in patients with non-small cell lung cancer

BACKGROUND/AIMS@#We investigated the time taken for patients with metastatic non-small cell lung cancer (NSCLC) to develop brain metastases (BM), as well as their subsequent overall median survival following diagnosis, considering the epidermal growth factor receptor (EGFR) mutational status.@*METHODS@#We retrospectively investigated the medical records of 259 patients diagnosed with advanced NSCLC from January 2010 to August 2013, who were tested for EGFR mutations. The time from the diagnosis of advanced NSCLC to the development of BM and the overall median survival after BM development (BM-OS) were evaluated and compared by EGFR mutational status.@*RESULTS@#Sixty-seven patients (25.9%) developed BM. Synchronous BM occurred more often in patients with EGFR mutation type (MT) (n = 20, 27.4%) compared with EGFR wild type (WT) (n = 27, 14.5%, p < 0.009). The median BM-OS was significantly longer in patients with EGFR MT than in those with EGFR WT (25.7 months vs. 3.8 months, p < 0.001), and a similar trend was noticed for patients with synchronous BM (25.7 months for EGFR MT vs. 6.8 months for EGFR WT, p < 0.001). However, in patients with metachronous BM development, the difference in BM-OS between patients with EGFR MT (14.6 months) and EGFR WT (2.5 months) did not reach statistical significance (p = 0.230).@*CONCLUSIONS@#Synchronous BM was more common in NSCLC patients with EGFR MT than in those with EGFR WT. However, EGFR mutations were associated with significantly longer median BM-OS, especially when the brain was the first metastatic site.

Comparison of differences in microbial compositions between negative controls and subject samples with varying analysis configurations

PURPOSE: Identifying microbial communities with 16S ribosomal RNA (rRNA) gene sequencing is a popular approach in microbiome studies, and various software tools and data resources have been developed for microbial analysis. Our aim in this study is investigating various available software tools and reference sequence databases to compare their performance in differentiating subject samples and negative controls. METHODS: We collected 4 negative control samples using various acquisition protocols, and 2 respiratory samples were acquired from a healthy subject also with different acquisition protocols. Quantitative methods were used to compare the results of taxonomy compositions of these 6 samples by varying the configuration of analysis software tools and reference databases. RESULTS: The results of taxonomy assignments showed relatively little difference, regardless of pipeline configurations and reference databases. Nevertheless, the effect on the discrepancy was larger using different software configurations than using different reference databases. In recognizing different samples, the 4 negative controls were clearly separable from the 2 subject samples. Additionally, there is a tendency to differentiate samples from different acquisition protocols. CONCLUSION: Our results suggest little difference in microbial compositions between different software tools and reference databases, but certain configurations can improve the separability of samples. Changing software tools shows a greater impact on results than changing reference databases; thus, it is necessary to utilize appropriate configurations based on the objectives of studies.

Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. MATERIALS AND METHODS: Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m(2) of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months. RESULTS: A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFR mutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. CONCLUSION: Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

A Case of Malignant Granular Cell Tumor in the Sigmoid Colon

Granular cell tumor (GCT) is an uncommon, usually benign neoplasm; however, a malignant potential has been described. Malignant GCT is an extremely rare neoplasm showing rapid growth and invasion into adjacent muscles, lymph nodes, or vessels, or even distant metastasis. We recently experienced a case of a histologically benign or atypical but clinically malignant GCT, with invasion of the lymph nodes and vessels in the sigmoid colon, diagnosed by segmental colon resection with lymph node dissection. We also performed a review of relevant medical literature.

Annual Change in Pulmonary Function and Clinical Characteristics of Combined Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis: Over a 3-Year Follow-up / 결핵및호흡기질환

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) have different pulmonary function tests (PFTs) and outcomes than idiopathic pulmonary fibrosis (IPF). The intention of this study was to identify unknown differences between CPFE and IPF by a retrospective comparison of clinical data including baseline and annual changes in pulmonary function, comorbidities, laboratory findings, clinical characteristics and cause of hospitalization. METHODS: This study retrospectively enrolled patients with CPFE and IPF who had undergone PFTs once or several times per year during a follow-up period of three years. Baseline clinical characteristics and the annual changes in the pulmonary function during the follow-up period were compared between 26 with CPFE and 42 patients with IPF. RESULTS: The baseline ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) in patients with CPFE was lower than that in patients with IPF (78.6+/-1.7 vs. 82.9+/-1.1, p=0.041). The annual decrease in FEV1/FVC in the CPFE was significantly higher than in the IPF. The annual decreases in diffusion capacity of carbon monoxide and FVC showed no significant differences between the two groups. The symptom durations of cough and sputum were in the CPFE significantly lower than in the IPF. The serum erythrocyte sedimentation rate level at the acute stage was significantly higher than in the IPF. There were no significant differences in the hospitalization rate and pneumonia was the most common cause of hospitalization in both study groups. CONCLUSION: The annual decrease of FEV1/FVC was in patients with CPFE significantly higher than in the patients with IPF.

Annual Change in Pulmonary Function and Clinical Characteristics of Combined Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis: Over a 3-Year Follow-up / 결핵및호흡기질환

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) have different pulmonary function tests (PFTs) and outcomes than idiopathic pulmonary fibrosis (IPF). The intention of this study was to identify unknown differences between CPFE and IPF by a retrospective comparison of clinical data including baseline and annual changes in pulmonary function, comorbidities, laboratory findings, clinical characteristics and cause of hospitalization. METHODS: This study retrospectively enrolled patients with CPFE and IPF who had undergone PFTs once or several times per year during a follow-up period of three years. Baseline clinical characteristics and the annual changes in the pulmonary function during the follow-up period were compared between 26 with CPFE and 42 patients with IPF. RESULTS: The baseline ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) in patients with CPFE was lower than that in patients with IPF (78.6+/-1.7 vs. 82.9+/-1.1, p=0.041). The annual decrease in FEV1/FVC in the CPFE was significantly higher than in the IPF. The annual decreases in diffusion capacity of carbon monoxide and FVC showed no significant differences between the two groups. The symptom durations of cough and sputum were in the CPFE significantly lower than in the IPF. The serum erythrocyte sedimentation rate level at the acute stage was significantly higher than in the IPF. There were no significant differences in the hospitalization rate and pneumonia was the most common cause of hospitalization in both study groups. CONCLUSION: The annual decrease of FEV1/FVC was in patients with CPFE significantly higher than in the patients with IPF.

A Case of Primary Mature Teratoma of the Rectum

A mature teratoma is a tumor composed of normal derivatives of all three germ layers, and usually occurs in ovaries, testes, or mediastinum. Mature teratoma of the gastrointestinal tract occurs less frequently, and case reports of primary mature teratoma of the rectum have not been published much. Here, we report a 65-year-old woman patient presented with lower abdominal discomfort. Colonoscopy revealed a pedunculated polypoid tumor arising from the rectum with hairs on its surface, and endoscopic ultrasound revealed an exophytic pattern bulging from the serosa. The tumor was removed surgically and confirmed histologically as a benign, primary mature teratoma of the rectum.

A Case of Lupus Pneumonitis Therapy in a Patient with Acute Systemic Lupus Erythematosus / 대한내과학회지

Systemic lupus erythematosus is a connective tissue disease with multiple organ involvement due to atypical creation of an antibody to an intracellular component. Although it can directly invade respiratory organs, such as the pleura, pulmonary parenchyma, trachea, pulmonary vessels, and pulmonary muscle, pulmonary involvement is mostly secondary to infection after immunosuppressant use, and pulmonary parenchyma invasion due to an immune response is relatively rare. This is a case report of acute lupus pneumonitis in a patient with systemic lupus erythematosus who was successfully treated with steroid therapy.

A Case of Lupus Pneumonitis Therapy in a Patient with Acute Systemic Lupus Erythematosus / 대한내과학회지

Systemic lupus erythematosus is a connective tissue disease with multiple organ involvement due to atypical creation of an antibody to an intracellular component. Although it can directly invade respiratory organs, such as the pleura, pulmonary parenchyma, trachea, pulmonary vessels, and pulmonary muscle, pulmonary involvement is mostly secondary to infection after immunosuppressant use, and pulmonary parenchyma invasion due to an immune response is relatively rare. This is a case report of acute lupus pneumonitis in a patient with systemic lupus erythematosus who was successfully treated with steroid therapy.

A Case of Capecitabine-Induced Sarcoidosis / 결핵및호흡기질환

Sarcoidosis is an inflammatory disease involving multiple-organs with an unknown cause. The new onset of sarcoidosis associated with therapeutic agents has been observed in 3 clinical settings; tumor necrosis factor antagonists in autoimmune rheumatologic diseases, interferon alpha with or without ribavirin in patients with chronic hepatitis C or melanoma, and antineoplastic agent-associated sarcoidosis in patients with hematologic malignancies. Here, we report a female patient who developed sarcoidosis after capecitabine treatment as an adjuvant chemotherapy for sigmoid colon cancer. To our knowledge, this is the first report of a capecitabine-induced sarcoidosis.

A Case of Balsalazide-Induced Limited Form of Granulomatosis with Polyangiitis with Bronchiolitis Obliterans Organizing Pneumonia-like Variant in Ulcerative Colitis / 결핵및호흡기질환

5-Aminosalicylate agents are the main therapeutic agents for ulcerative colitis. Balsalazide is a prodrug of 5-aminosalicylate and has fewer side effects than the other 5-aminosalicylate agents. Pulmonary complications resembling granulomatosis with polyangiitis in ulcerative colitis are extremely rare. Here, we report a patient with ulcerative colitis on balsalazide presenting respiratory symptoms and multiple pulmonary nodules from a chest radiography that was pathologically diagnosed with a limited form of granulomatosis with polyangiitis with bronchiolitis obliterans organizing pneumonia-like variant. To our knowledge, this is the first report of a balsalazide-induced limited form of granulomatosis with polyangiitis with bronchiolitis obliterans organizing pneumonia-like variant.

Inhibition of PKC Epsilon Attenuates Cigarette Smoke Extract-Induced Apoptosis in Human Lung Fibroblasts (MRC-5 Cells) / 결핵및호흡기질환

BACKGROUND: It is known that cigarette smoke (CS) causes cell death. Apoptotic cell death is involved in the pathogenesis of CS-related lung diseases. Some members of the protein kinase C (PKC) family have roles in cigarette smoke extract (CSE)-induced apoptosis. This study was conducted to investigate the role of PKC epsilon in CSE-induced apoptosis in human lung fibroblast cell line, MRC-5. METHODS: Lactate dehydrogenase release was measured using a cytotoxicity detection kit. The MTT assay was used to measure cell viability. Western immunoblot, Hoechst 33342 staining and flow cytometry were used to demonstrate the effect of PKCepsilon. Caspase-3 and caspase-8 activities were determined using a colorimetric assay. To examine PKCepsilon activation, Western blotting was performed using both fractions of membrane and cytosol. RESULTS: We showed that CSE activated PKCepsilon by demonstrating increased expression of PKCepsilon in the plasma membrane fraction. Pre-treatment of PKCepsilon peptide inhibitor attenuated CSE-induced apoptotic cell death, as demonstrated by the MTT assay (13.03% of control, 85.66% of CSE-treatment, and 53.73% of PKCepsilon peptide inhibitor-pre-treatment, respectively), Hoechst 33342 staining, and flow cytometry (85.64% of CSE-treatment, 53.73% of PKCepsilon peptide inhibitor-pre-treatment). Pre-treatment of PKCepsilon peptide inhibitor reduced caspase-3 expression and attenuated caspase-3, caspase-8 activity compared with CSE treatment alone. CONCLUSION: PKCepsilon seem to have pro-apoptotic function and exerts its function through the extrinsic apoptotic pathway in CSE-exposed MRC-5 cells. This study suggests that PKCepsilon inhibition may be a therapeutic strategy in CS-related lung disease such as chronic obstructive pulmonary disease.

Association of p53 Expression with Metabolic Features of Stage I Non-Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Recent evidences have revealed metabolic functions of p53 in cancer cells; adaptation or survival to metabolic stress and metabolic shift toward oxidative phosphorylation. However, further studies in clinical setting are needed. We investigated whether p53 protein expression, as a surrogate marker for loss of p53 function, is associated with metabolic features of stage I non-small cell lung cancer (NSCLC), focusing on tumor necrosis and maximal standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography. METHODS: Clinical information was obtained from retrospective review of medical records. p53 expression was assessed by immunohistochemical staining. RESULTS: p53 protein expression was detected in 112 (46%) of 241 NSCLC cases included in this study. p53 expression was independently associated with the presence of necrosis (odds ratio [OR], 2.316; 95% confidence interval [CI], 1.215~4.416; p=0.011). Non-adenocarcinoma histology (OR, 8.049; 95% CI, 4.072~15.911; p<0.001) and poorly differentiation (OR, 6.474; 95% CI, 2.998~13.979; p<0.001) were also independently associated with the presence of necrosis. However, p53 expression was not a significant factor for SUVmax. CONCLUSION: p53 protein expression is independently associated with the presence of necrosis, but not SUVmax.

Long-term Maintenance of Smoking Cessation and Related Factors of Relapse / 가정의학회지

BACKGROUND: Long-term maintenance of smoking cessation is important to reduce smoking related diseases. There are few studies that evaluated long-term maintenance and related factors. For effective cessation treatment, we analyzed the relapse pattern after cessation and related factors. METHODS: We selected people who visited a health care center more than two times between January 1995 and December 2006 and who have succeeded in cessation after the first visit. Telephone survey was done and their medical records was analyzed. A total of 308 people whose medical records corresponded to the results of the telephone survey were finally included and analyzed. RESULTS: The mean follow-up duration was 112 months and the mean age of the first visit was 47.9 years. The median maximum duration of abstinence was 5.50 years, and the annual hazard ratio of relapse was about 2.5-4.2% from two to seven years of duration of abstinence. Mean age of smoking onset was 22.9 years, the mean smoking duration was 24.5 years, and the mean smoking amount per a day was 20.0 cigarettes. In single-variate analysis, the total number of cessation success, the age of smoking onset, the mean smoking duration, the mean smoking amount per day, the cessation method, the reason for trying cessation were related with the long-term cessation maintenance. In multivariate analysis, the total number of success for cesstion, the reason for trying cessation, the cessation method, the mean number of cigarettes per day were related. CONCLUSION: The experience of relapse, the motive of cessation and self-willingness were shown to be important for long-term maintenance of smoking cessation.

A Case of Pulmonary Choriocarcinoma / 결핵및호흡기질환

Pulmonary choriocarcinoma is a very rare tumor in men. Herrein, the case of a pulmonary choriocarcinoma in 39-year-old man, and whether it had a primary nature, is reported. He denied any prior medical illness, but was admitted to our hospital with a history of a cough, and progressive dyspnea and hemoptysis 2 and 1 week duration, respectively. Chest radiographs on admission revealed a huge lung mass, 10 cm in diameter, in the left upper lung field, with left pleural effusion. Although biopsies using several diagnostic methods for the pathological confirmation were attempted, the pathology was not confirmed. Finally, the patient died after 2 months of regression. An autopsy of the lung was then performed.

The Prevalence of Human Papillomavirus Infection in Korean Non-Small Cell Lung Cancer Patients

Human papillomavirus (HPV) infection is a co-carcinogen of lung cancer and contributes to its pathogenesis. To evaluate the prevalence of HPV infection, polymerase chain reaction (PCR) was employed to detect HPV 16, 18, and 33 DNA in tumor tissues of 112 patients with non-small cell lung cancer (NSCLC) who underwent curative surgery from Jan. 1995 to Dec. 1998 at Severance Hospital, Seoul, Korea. The patients consisted of 90 men and 22 women. Nineteen patients were under 50 years old (17%), and 92 patients (82%) were smokers. Fifty-three patients had adenocarcinomas, while 59 patients had non-adenocarcinomas. Early stage (I and II) cancer was found in 64 patients (57.1%) and advanced stage (III and IV) found in 48 (42.9%). The prevalence of HPV 16, 18, and 33 were 12 (10.7%), 11 (9.8%), and 37 (33.0%), respectively. Smoking status, sex, and histologic type were not statistically different in the presence of HPV DNA. The presence of HPV 16 was more common in younger patients and HPV 18 was more common in advanced stage patients. This study showed that the prevalence rate of HPV 16 and 18 infections in NSCLC tissue was low, suggesting HPV 16 and 18 infections played a limited role in lung carcinogenesis of Koreans. However, the higher prevalence of HPV 33 infections in Korean lung cancer patients compared to other Asian and Western countries may be important and warrants further investigation.

The Effect and Safety of Alveolar Recruitment Maneuver using Pressure-Controlled Ventilation in Acute Lung Injury and Acute Respiratory Distress Syndrome / 결핵및호흡기질환

BACKGROUND: Alveolar recruitment (RM) is one of the primary goals of respiratory care for an acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The purposes of alveolar recruitment are an improvement in pulmonary gas exchange and the protection of atelectrauma. This study examined the effect and safety of the alveolar RM using pressure control ventilation (PCV) in early ALI and ARDS patients. METHODS: Sixteen patients with early ALI and ARDS who underwent alveolar RM using PCV were enrolled in this study. The patients' data were recorded at the baseline, and 20 minutes, and 60 minutes after alveolar RM, and on the next day after the maneuver. Alveolar RM was performed with an inspiratory pressure of 30 cmH2O and a PEEP of 20 cmH2O in a 2-minute PCV mode. The venous O2 saturation, central venous pressure, blood pressure, pulse rate, PaO2/FiO2 ratio, PEEP, and chest X-ray findings were obtained before and after alveolar RM. RESULTS: Of the 16 patients, 3 had extra-pulmonary ALI/ARDS and the remaining 13 had pulmonary ALI/ARDS. The mean PEEP was 11.3 mmHg, and the mean PaO2/FiO2 ratio was 130.3 before RM. The PaO2/FiO2 ratio increased by 45% after alveolar RM. The PaO2/FiO2 ratio reached a peak 60 minutes after alveolar RM. The PaCO2 increased by 51.9 mmHg after alveolar RM. The mean blood pressure was not affected by alveolar RM. There were no complications due to pressure injuries such as a pneumothorax, pneumomediastinum, and subcutaneous emphysema. CONCLUSION: In this study, alveolar RM using PCV improved the level of oxygenation in patients with an acute lung injury and acute respiratory distress syndrome. Moreover, there were no significant complications due to hemodynamic changes and pressure injuries. Therefore, alveolar RM using PCV can be applied easily and safely in clinical practice with lung protective strategy in early ALI and ARDS patients.

Validation of the Korean Version of the St. George's Respiratory Questionnaire for Patients with Chronic Respiratory Disease / 결핵및호흡기질환

BACKGROUND: The "health-related quality of life" (HRQL) for patients with chronic respiratory disease has been emphasized, because chronic respiratory disease (CRD) is chronic and progressive, and it finally causes disability. HRQL instruments may be useful for monitoring patients' progress or for determining the most appropriate choice of treatment. We describe the adapting St George's Respiratory Questionnaire (SGRQ), which is a self-administered questionnaire developed by Jones et al. (1991), into the Korean version for covering three domains of health for the patients suffering with airways disease. METHOD: We obtained the original SGRQ from the author after gaining permission. For adaptation, we created an expert panel and translated the original questionnaire into Korean language. The translated questionnaire was then back-translated by bilingual experts and we compared it with the original questionnaire. After correction and feasibility testing, 74 patients with chronic respiratory disease (COPD, asthma, destroyed lung) completed the Korean version of the SGRQ. The clinical status of each patients was evaluated concurrently with measurement of their health status. RESULT: The Korean version of the SGRQ was acceptable and easy to understand. Cronbach's alpha reliability coefficient was 0.92 for the overall scale and 0.63 for the "Symptoms", subscale, 0.87 for the "Activity", subscale, and 0.89 for the "Impacts" subscales. The correlation coefficients between the overall score and the Borg scale score, oxygen saturation, and forced expiratory volume in one second (FEV(1)) were 0.52, -0.32 and -0.26, respectively. These results support that the Korean SGRQ was correlated with other measurements. CONCLUSION: The Korean SGRQ was reliable and valid for patients with chronic respiratory disease, such as COPD, asthma, and destroyed lung. The SGRQ score was well correlated with other respiratory measurements as well. Although further studies should complete the adaptation work, our results suggest that the SGRQ may be used in Korea and also for international studies involving Korean CRD patients.

A Case of Pulmonary Metastasis of a Dermatofibrosarcoma Protuberans / 결핵및호흡기질환

Dermatofibrosarcoma protuberans (DFPS) is a locally aggressive skin tumor with a very low incidence in the general population. This tumor has a remarkable tendency to recur, However, a metastasis is rare. We report a case of DFPS with a pulmonary metastasis in 28-year-old man. The pulmonary metastasis developed 5 years after a complete resection of the primary skin tumor. We reviewed the clinical manifestations and treatment of DFPS, and highlight the need for a long-term follow-up examination for metastases after a wide excision of these lesions.

Risk Factors of Recurrent Hemoptysis after Bronchial Artery Embolization / 결핵및호흡기질환

No abstract available.