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BackgroundTumour-unrelated, virus-specific bystander CD8+T cells were recently shown to be abundant among tumour-infiltrating lymphocytes (TILs). However, their roles in tumour immunity have not been elucidated yet.MethodsWe studied the characteristics of bystander CD8+TILs from non-small cell lung cancer (NSCLC) tissues (N=66) and their activation by interleukin (IL)-15 to repurpose them for tumour immunotherapy.ResultsWe show that bystander CD8+TILs specific to various viruses are present in human NSCLC tissues. We stimulated CD8+TILs ex vivo using IL-15 without cognate antigens and found that IL-15 treatment upregulated NKG2D expression on CD8+TILs, resulting in NKG2D-dependent production of interferon (IFN)-γ (p=0.0006). Finally, we tested whether IL-15 treatment can control tumour growth in a murine NSCLC model with or without a history of murine cytomegalovirus (MCMV) infection. IL-15 treatment reduced the number of tumour nodules in the lung only in mice with MCMV infection (p=0.0037). We confirmed that MCMV-specific bystander CD8+TILs produced interferon (IFN)-γ after IL-15 treatment, and that IL-15 treatment in MCMV-infected mice upregulated tumour necrosis factor-α and IFN-γ responsive genes in tumour microenvironment.ConclusionThus, the study demonstrates that bystander CD8+TILs can be repurposed by IL-15 for tumour immunotherapy.

Tumour-unrelated, virus-specific bystander CD8We studied the characteristics of bystander CD8We show that bystander CD8Thus, the study demonstrates that bystander CD8

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.

Introduction: Previously, transcriptomic profiling studies have shown distinct molecular subtypes of glioblastomas. It has also been suggested that the recurrence of glioblastomas could be achieved by transcriptomic reprograming of tumors, however, their characteristics are not yet fully understood. Here, to gain the mechanistic insights on the molecular phenotypes of recurrent glioblastomas, gene expression profiling was performed on the 43 cases of glioblastomas including 15 paired primary and recurrent cases. Materials and Methods: Total RNA was extracted from frozen tumor section. For microarray experiments, cRNA was used for hybridization to a human HT12-v4 Illumina Beadchip gene expression array and fluorescence signals were obtained using Illumina bead Array Reader confocal scanner. For validation analysis, two independent gene expression data of REMBRANDT and TCGA were obtained from their websites, respectively. For subtype prediction, three independent methods of unsupervised hierarchical clustering, consensus clustering, and nearest template prediction were applied. The functional profiling of biological function and signaling pathways were performed using DAVID software. Results: Unsupervised clustering analyses revealed two subtypes of G1 and G2, which were characterized by proliferation and neuron-like gene expression traits, respectively. While the primary tumors were classified as G1 subtype, the recurrent glioblastomas showed two distinct expression types. Compared to paired primary tumors, the recurrent tumors in G1 subtype did not show expression alteration. By contrast, the recurrent tumors in G2 subtype showed expression changes from proliferation type to neuron-like one. We also observed the expression of stemness-related genes in G1 recurrent tumors and the altered expression of DNA-repair genes (i.e., AURK, HOX, MGMT, and MSH6) in the G2 recurrent tumors, which might be responsible for the acquisition of drug resistance mechanism during tumor recurrence in a subtype-specific manner. Conclusions: We suggest that recurrent glioblastomas may choose two different strategies for transcriptomic reprogramming to escape the chemotherapeutic treatment during tumor recurrence. Our results might be helpful to determine personalized therapeutic strategy against heterogeneous glioma recurrence.

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 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.

Purpose Genexol-PM is a Cremorphor EL (CrEL)-free polymeric micelle formulation of paclitaxel that allows higher-dose administration with less hypersensitivity. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients as a first-line treatment. Patients and methods This is a prospective, single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on day 1 and day 8 of a 3-week cycle. Six cycles of chemotherapy were planned unless there was disease progression. The primary endpoint was overall response rate. Results Forty-three patients received the study drugs with a median of 4 cycles per patient (range 1–6). The overall response rate was 46.5 %. The median progression-free survival was 4.0 months (95 % CI 2.0–6.0 months), and median overall survival was 14.8 months (95 % CI 9.1–20.5 months). The most common toxicities were anemia (n = 29, 67 %), asthenia (n = 17, 40 %), myalgia (n = 16, 37 %), peripheral neuropathy (n = 15, 35 %), and diarrhea (n = 12, 30 %). The most common grade 3/4 adverse events were neutropenia (n = 7, 16 %) and pneumonia (n = 5, 12 %). Two patients died of pneumonia and dyspnea. Conclusions CrEL-free paclitaxel in combination with gemcitabine demonstrated favorable antitumor activity with little emetogenicities in non-small cell lung cancer patients. However, frequent grade 3/4 toxicities were observed, and safety should be evaluated thoroughly in future studies.

IL-15 is a homeostatic cytokine that induces proliferation of NK cells and memory CD8+ T cells. Recently, clinical trials using various forms of IL-15 in combination with immune checkpoint inhibitors in multiple intractable cancers are on progress. In the present study, we examined effects of IL-15 on tumor-infiltrating CD8+ T cells obtained from human non-small cell lung cancer (NSCLC; n = 20) and synergic effects of IL-15 in combination with anti- PD-1 blocking antibodies. More than 80% of tumor-infiltrating CD8+ T cells expressed PD-1, indicating that they are exhausted. We stimulated tumor-infiltrating CD8+ T cells with anti-CD3 antibodies in the absence or presence of anti-PD-1 blocking antibodies and IL-15 and found that anti-PD-1 treatment increased anti-CD3-stimulated proliferation of tumor-infiltrating CD8+ T cells, indicating that tumor-infiltrating CD8+ T cells were reinvigorated by anti-PD-1. Moreover, IL-15 further enhances anti-PD-1-induced reinvigoration of tumor-infiltrating CD8+ T cells in a dose-dependent manner. These findings indicate that IL-15 might increase therapeutic effects of anti-PD-1 by synergistically enhancing anti-PD-1-induced reinvigoration of tumor-infiltrating CD8+ T cells.

Pneumonia is a important cause of hospitalized excerbation COPD patients. Also, virus or influenza are frequently complicated by bacterial pneumonia. We examined the risk factors and clinical characteristics contributing to bacterial co-infection with virus or influenza among the hospitalized pneumonia with COPD patients. Pneumonia in COPD patients were admitted to gachon university Gil Medical Center from 1 January 2013 to 30 August 2014. They were divided into 2 groups based upon the presence of virus or influenza. One hudred fifty four patients identified virus or influenza(Virus group). Three hundred six patients not identified virus or influenza(control group). Retrospectively, we analysed the clinical characteristics, the results of blood examination and lung function tests from medical records of both groups. Mean age of each group was 74.4±9.7 years in virus group and 72.0 ± 9.7 years in control group. Age and female ratio was significantly higher in virus group. Pack year, smoking history and tuberculosis history were significantly lower in virus group. Virus group have significantly higher level of Blood pressure, serum albumin, P, hemoglobin, stable FVC(%) and FEV 1 (%). Virus group have significantly lower level of FVC(L), FEV 1 (L), FEV 1 (%) and lymphocyte when they hospitalized. The two groups have no significant difference in other clinical features: hypertenstion, diabetes mellitus, ischemic heart disease, survival, hosptital day, body mass index, weight. Age, female, smoking and tuberculosis history may be associated with virus or influenza infection among the hospitalized pneumonia with COPD patients.

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.

Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection or prevention strategies are urgently needed to increase survival. Hyperplasia is the first morphologic change that occurs in the bronchial epithelium during lung cancer development, followed by squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor. This study was designed to determine the molecular mechanisms that control bronchial epithelium hyperplasia. Using primary normal human tracheobronchial epithelial (NHTBE) cells cultured by using the 3-dimensional (3D) organotypic method, we found that the epidermal growth factor receptor (EGFR) ligands, EGF, TGF-α, and amphiregulin induced hyperplasia, as determined by cell proliferation and multilayered epithelium formation. We also found that EGF induced increased cyclin D1 expression, which plays a critical role in bronchial hyperplasia; this overexpression was mediated by activating the mitogen-activated protein kinase pathway but not the phosphoinositide 3-kinase/Akt signaling pathway. Erlotinib, an EGFR tyrosine kinase inhibitor, and U0126, a MAP/ERK kinase (MEK) inhibitor, completely inhibited EGF-induced hyperplasia. Furthermore, a promoter analysis revealed that the activator protein-1 transcription factor regulates EGF-induced cyclin D1 overexpression. Activator protein-1 depletion by using siRNA targeting its c-Jun component completely abrogated EGF-induced cyclin D1 expression. In conclusion, we showed that bronchial hyperplasia can be modeled in vitro by using primary NHTBE cells maintained in a 3D organotypic culture. EGFR and MEK inhibitors completely blocked EGF-induced bronchial hyperplasia, suggesting that they have a chemopreventive role. Cancer Prev Res; 4(8); 1306–15. ©2011 AACR.

In this study, we have developed a ligand-based in-silico prediction model to classify chemical structures into hERG blockers using Bayesian and random forest modeling methods. These models were built based on patch clamp experimental results. The findings presented in this work indicate that Laplacian-modified naive Bayesian classification with diverse selection is useful for predicting hERG inhibitors when a large data set is not obtained.

Thoracic endometriosis is a rare disorder characterized by the presence of functioning endometrial tissue within the pleura, lung parenchyma, or the airways. We report a case of catamenial hemoptysis with a rare presentation, that is, as a solitary pulmonary nodule with an internal cavity and surrounding ground glass opacity.

Summary Purpose Skeletal muscle depletion is an important prognostic factor in patients with chronic obstructive pulmonary disease (COPD); a recent study demonstrated significant correlations between pectoralis muscle area on an axial CT image and COPD-related traits. The purpose of this study was to evaluate the relation between pectoralis muscle areas on CT scans and total body skeletal muscle mass (SMM) in healthy subjects. Methods For 434 subjects that underwent a low-dose chest CT and bioelectrical impedance analysis (BIA) during health screening from January to June of 2014, cross-sectional area of pectoralis muscles were measured in CT scans. Pearson's correlation and multiple linear regression analysis were used to assess the relationship between cross-sectional CT areas of pectoralis muscles and BIA-assessed SMMs. Results Mean age was 50 ± 10 years (78·8% were male). The mean cross-sectional area of pectoralis muscles was 24·1 cm2 ± 6·8. A moderate correlation was observed between pectoralis muscle area and BIA-based SMM (r = 0·665, P

Background A recent cytogenetic analysis of non-small cell lung cancer revealed hot-spot regions for deletion on the long arm of chromosome 5 and suggested the existence of putative tumor suppressor genes in that region. However, similar studies on genetic alterations in large cell neuroendocrine carcinoma (LCNEC) have been very limited. To our knowledge, this is the first report to screen for the loss of heterozygosity (LOH) and to examine the location of putative tumor suppressor genes on chromosome 5q in LCNEC. Objectives To identify tumor suppressor loci on chromosome 5q in LCNEC by microsatellite analysis. Patients and methods Microsatellite instability and LOH in tumor and normal tissue samples from 13 patients with LCNEC, who had undergone surgical resections, were analyzed by polymerase chain reaction using a panel of 19 microsatellite DNA markers spanning chromosome 5q. Results LOH was found in all of the 13 tumors (100%) in at least one informative marker tested. The following four common minimally deleted regions were noticed on chromosome 5q: 5q14.3-q21.1; 5q22.2-q23.1; 5q23.3-q33.2; and 5q35.1-q35.2. Three of 13 individual tumors (23.1%) exhibited shifted bands for at least one of the tested microsatellite markers. Shifted bands occurred in 6 of 224 loci (2.7%) tested. Conclusion These data suggest the presence of at least four tumor suppressor loci on chromosome 5q in LCNEC, and further investigations into cloning candidate tumor suppressor genes are warranted.

Chronic pulmonary aspergillosis (CPA) is a severe pulmonary disease caused by aspergillus fumigatus infection. However, immune responses in CPA patients remained to be elucidated. In humans, the CD4+Foxp3+regulatory T cell (Treg) population are classified into the following three subsets based on their expression of CD45RA and Foxp3: CD45RA+Foxp3lo resting Treg cells (subset I), CD45RA−Foxp3high activated Treg cells (subset II), and CD45RA−Foxp3locytokine-secreting non-suppressive cells (subset III). In the present study, we investigated these three CD4+Foxp3+cell subsets and their clinical implication in CPA patients. The frequency of total CD4+Foxp3+ cells did not differ between CPA patients and healthy controls. Whereas the frequency of subset I or II also did not differ between the two groups, the frequency of subset III was significantly increased in CPA patients compared with healthy controls. Interestingly, IL-17A production was observed in the subset III CD4+Foxp3+ T cells, and the frequency of subset III significantly correlated with IL-17A production from the CD4+ T cell population. Moreover, we found that better clinical prognosis, evaluated by less hospitalization incident, was associated with higher IL-17A production from the CD4+ T cell population and higher frequency of subset III CD4+Foxp3+ cells among CPA patients. In summary, the frequency of IL-17A-producing CD4+Foxp3+ T cells was increased and correlated with the frequency of IL-17A+ CD4+ T cells, and the higher frequency of IL-17A-producing CD4+Foxp3+ T cells was related with better clinical prognosis. We suggest that IL-17A-producing CD4+Foxp3+ T cells (subset III) may have a role in Th17 regulation and antifungal immune responses in CPA patients.

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/m² 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.

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.

BACKGROUND. Adenosquamous carcinoma of the lung is composed of adenocarcinomatous and squamous cell carcinomatous components. The epidermal growth factor receptor (EGFR) mutations occur mostly in adenocarcinomas and rarely in squamous cell carcinoma of lung. Attempts to investigate the EGFR mutation status in each component of adenosquamous carcinoma and to characterize the patients according to mutation status may help to understand the histogenesis of adenosquamous carcinoma. METHODS. The mutation status of EGFR kinase domain from exon 18 to 21 was investigated in 25 Korean patients with adenosquamous carcinoma by polymerase chain reaction–single strand conformation polymorphism using the tissues of each component from the adenosquamous carcinoma tumor. Clinicopathologic characteristics of the patients according to the status of EGFR mutations were compared. RESULTS. EGFR mutations were identified in 11 (44%) patients: 9 mutations were in exon 19, 1 in exon 20, and 1 in exon 21. EGFR mutations were significantly more frequent (P = .005) in women (n = 8, 80%) than men (n = 3, 20%). Never-smokers (n = 8, 62%) had EGFR mutations more commonly than smokers (n = 3, 25%; P = .111). Identical EGFR mutations in both components of adenosquamous carcinoma were confirmed by nucleotide sequencing. CONCLUSIONS. The frequency of EGFR mutation and clinicopathologic characteristics of the EGFR mutants in adenosquamous carcinoma are similar to those of Asian patients with adenocarcinomas. Identical EGFR mutations in both components suggest the possibility of monoclonality in the histogenesis of adenosquamous carcinoma. Cancer 2007;109:581–587. © 2006 American Cancer Society.

A chemosensitivity test can reflect the differences in responses of individual cancer patients to chemotherapeutic agents. The adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is an accurate method, which does not require a large amount of tissue specimen. So far, no studies have evaluated the utility of the ATP-CRA in Korea. Therefore, we investigated the clinical usefulness of the ATP-CRA in 53 patients with lung cancer.Tumor tissues were obtained from bronchoscopic biopsies or surgical resections. The validity of ATP-CRA was assessed focusing on the success rate, experimental error level (intraassay mean coefficient of variation [CV]) and reproducibility.The overall success rate of ATP-CRA was 90.6% (48/53). Normal cells were effectively eliminated from the tumor tissues with the use of ficoll gradient centrifugation and immunomagnetic separation, which was confirmed using loss of heterozygosity analysis of the 3p deletion. The mean CV of ATP assays was 10.5+/-4.6%. The reproducibility of ATP assays was 94+/-3.8%. The results of the ATP assays were reported to physicians within 7 days of specimen collection. More than 6 anticancer drugs were tested on the tumor specimens obtained from bronchoscopic biopsies.The ATP-CRA is a stable, accurate and potentially practical chemosensitivity test in patients with lung cancer.

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.

Correspondence to Ji-Min Oh, M.D. Department of Internal Medicine, SAM Medical Center, 9 Samdug-ro, Manan-gu, Anyang 430-733, Korea Tel: +82-31-467-9226, Fax: +82-31-467-9198, E-mail: ninijang@naver.com Copyrightc 2014 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 전신 홍반 루푸스 환자에게 발생한 급성 루푸스 폐렴 치료 1예

Pulmonary aspergillosis may be classified under three categories, depending upon whether the host is atopic or immunocompromised: invasive aspergillosis, allergic bronchopulmonary aspergillosis (ABPA) or aspergilloma. However, it is not always possible to effectively categorize this disease. We experienced a case of endobronchial aspergilloma, which was difficult to categorize, in a healthy male patient. The chest X-ray and computed tomography showed an ill-defined nodule mimicking lung cancer. Fiberoptic bronchoscopy revealed an aspergilloma without cavity formation in the left lower laterobasal segmental bronchial orifice. The aspergilloma was removed and the patient's symptoms were relieved. We present this unusual case with a review of the literature.

e19129 Background: Non-platinum doublet paclitaxel and gemcitabine has shown efficacy on par with platinum-based doublet regimens as first-line chemotherapy in advanced non-small cell lung cancer patients. Genexol-PM is a Cremorphor EL(CrEL)-free polymeric micelle formulation of paclitaxel. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients. Methods: This is a single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230mg/m2 on day 1 and gemcitabine 1000mg/m2 on day 1 and day 8 of a 3-week cycle as first-line chemotherapy. Six cycles of chemotherapy were administered unless there is a disease progression. The primary endpoint was response rate. Results: Forty-three patients received the study drugs with median of 4 cycles per patient (range, 1-6). Among 35 patients who received more than one cycle, mean dose intensity of CrEL-free paclitaxel and gemcitabine was 209 mg/m2/3-week and 1,853 mg/m2/3-week respectively. Overall response rate was 46.5%. The median progression free survival was 4.0 months (95% CI 2.0-6.0 months) and median overall survival was 14.8 months (95% CI 9.1-20.5 months). 18 patients (51%) experienced grade 3/4 adverse events, including neutropenia or febrile neutropenia (n=7), pneumonia (n=3), asthenia (n=3), peripheral neuropathy (n=2), diarrhea (n=1), skin rash (n=1), myalgia (n=1), pulmonary thromboembolism (n=1), LV dysfunction (n=1), and dyspnea with sudden death (n=1). Adverse events leading to drug discontinuation were occurred in 9 patients, among which 2 patients were died of adverse events (pneumonia, dyspnea with sudden death). Conclusions: CrEL-free paclitaxel in combination with gemcitabine demonstrated comparable antitumor activity with less emetogenicities in non-small cell lung cancer patients. Clinical trial information: NCT01770795.

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.

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 longterm maintenance of smoking cessation.

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.

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.

연구배경: 급성폐손상과 급성호흡곤란증후군 대상자에서 폐포모집술의 적절한 방법에 대해서는 정해진 것이 없다. 이 연구를 통해 폐포모집술들 중 압력조절환기법을 이용한 폐포모집술의 효과와 안정성을 확인하고자 하였다. 방 법: 급성폐손상 및 급성호흡곤란증후군에 해당하는 대상자들을 대상으로 압력조절환기 방식에서 30 cmH2O의 흡입압력과 20 cmH2O의 호기말양압으로 2분 동안 폐포모집술을 시행하였다. 동맥혈 산소분압, 정맥혈 산소포화도, 혈압과 맥박, 중심정맥압, 폐탄성, 호기말양압, 흉부 X-ray를 시술 전ㆍ후로 확인하였다. 결 과: 16명의 대상자들 중에서, 3명은 폐외 급성폐손상 및 급성호흡곤란증후군 대상자였고 나머지 13명은 폐내 급성폐손상 및 급성호흡곤란증후군 대상자였다. 평균 나이는 61.0±11.8세였고, 평균 APACHE II score는 21.6±11.9이었으며, SAPS score는 44.6±14이었다. 폐포모집술 시행 전, 평균 호기말양압은 11.3±1.5 mmHg이었으며 평균 동맥혈산소분압/흡입산소분율은 130.3±60.2이었다. 폐포모집술 시행 20분 후, 동맥혈산소분압/흡입산소분율의 비를 측정하여 50% 이상 상승한 경우를 반응군으로 50% 이하로 상승하거나 감소한 경우를 비반응군으로 분류하였다. 8명의 대상자들은 반응군이었고 8명의 대상자들은 비반응군이었다. 두 군간의 인구학적인 특성과 기계호흡의 패턴, APACHE II score, SAPS score, 동맥혈산소분압/흡입산소분율과 혈역동학적 특성 사이에는 차이가 없었다. 폐포모집술 이후, 동맥혈산소분압/흡입산소분율의 비는 상승하였다(p＜0.001). 그 최대치는 폐포모집술 이후 60분에서 관찰되었다. 동맥혈 이산화탄소분압은 상승하는 경향을 보였다(p=0.05). 폐포모집술 전ㆍ후의 평균동맥압의 차이는 없었다(p=0.08). 기흉 등의 압력 손상에 의한 합병증은 없었으며, 단 한 예에서만 혈압 저하로 인해 폐포모집술을 중단하였으나 수액 공급 후 바로 회복되었다. 결 론: 본 연구를 통해서, 압력조절환기를 이용한 폐포모집술은 급성폐손상 및 급성호흡곤란증후군 대상자에서 산소화의 개선을 보였다. 또한 혈역학적 부작용은 거의 없었으며 고압력에 의한 합병증은 없었다. 따라서 압력조절환기를 이용한 폐포모집술은 폐보호전략과 더불어 임상적인 유용성과 안전성이 있을 것으로 기대된다.

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.

연구배경: 만성폐질환 환자에서 삶의 질을 측정하는 도구로서 세인트조지 호흡기 설문(St George`s Respiratory Questionnaire;SGRQ)이 개발되어 치료효과를 판정하는 측정지표로 널리 사용되고 있으나 영어권국가에서 만들어 졌기 때문에 우리나라에서 동일하게 사용하는데 제한점을 가지고 있다. 따라서 이의 정확한 적용을 위해서 언어, 기술, 개념적인 관점을 고려하여 한국어 설문지를 만들고 이들의 타당도와 신뢰도를 평가하였다. 방법: 한국판 세인트조지 호흡기 설문은 번역, 역번역, 전문가 패널의 수정을 통해 완성되었고, 세브란스병원 호흡기내과를 방문한 환자를 대상으로 하여 이 설문을 시행하였다. 신뢰도 검정은 Cronbach`s α를 구하여 측정하였고 타당도는 폐기능검사, 6분보행검사, 호흡곤란지수와 산소포화도 검사를 동시에 시행하여 설문 검사결과와의 상관관계를 알아보았다. 결과: 74명의 환자를 대상으로 시행하였으며, 남녀 비는 2.2:1, 평균연령은 63.8±10.3세였다. 이 중 천식환자는 27명(36.5%), 만성폐쇄성폐질환 환자는 39명 (52.7%)이었고, 결핵에 의한 파괴 폐환자는 8명(10.8%)이었다. Cronbach`s α 값은 증상영역, 활동영역, 영향영역 및 총 점수에서 각각 0.63, 0.87, 0.89, 0.92 이였다. 총점수와 FEV1, FVC, 6분보행거리, 산소포화도, 호흡곤란지수와 유의한 상관관계를 보였다. 결론: 한국어판 세인트조지 호흡기 설문은 만성폐질환 및 천식과 같은 만성폐질환 환자에서 신뢰도가 높았고 총점수와의 상관관계는 6분보행검사 및 산소포화도에서 높음을 알수 있었고 폐기능 검사와의 상관계수는 원저인 세인트조지 호흡기설문 및 타 국가의 번역본 호흡기설문에서와 같이 높지 않음을 알 수 있었다. 따라서 우리나라에서도 호흡기질환의 삶의 질에 대한 치료효과 판정에 활용할 수 있을 것으로 기대된다.

Background : Delayed treatment of pulmonary tuberculosis is an important problem because it results in greater mortality and the nosocomial transmission of tuberculosis. This study was conducted to analyze the factors that contribute to the delayed treatment of pulmonary tuberculosis in a university hospital and we wanted to provide basic data for instituting an effective management program for tuberculosis. Methods : we retrospectively reviewed the medical records of 155 patients with smear-positive or culture-positive pulmonary tuberculosis and who were treated between May 1999 and October 1999. A case-control study was performed to analyze the factors. We then tried to follow up the patients in delayed treatment group via telephone for the purpose of assessing the therapeutic interventions. Results : Among 150 patients, 55 (37%) were included in the delayed treatment group. The factors associated with delayed treatment on the univariate analysis included age (61 vs 40 years old; p

Bronchiolitis obliterans organizing pneumonia (BOOP) is often diagnosed in patients with pneumonia who respond poorly to antibiotics. BOOP is often idiopathic, and the etiology of the remaining cases has been attributed to a wide range of agents or medical conditions. When a patient develops the clinical symptoms characteristic of BOOP, the medical team must endeavor to determine the etiology of this disease because it can be treated with glucocorticoid and avoidance of the causative agent. In particular, if BOOP is diagnosed during or after chemotherapy for a malignancy, the possible culprit agent can be the anti cancer drugs but other drugs used for supportive care must be also be considered. We report a case of BOOP that arose after CHOP chemotherapy and a filgrastim injection in a patient with a diffuse large B-cell lymphoma.

Hemangiopericytoma is a rare neoplasm that originates from small peri-capillary spindle shaped cells called pericytes. The most common sites of origin are the thigh, the pelvis and the retroperitoneum. A primary pulmonary hemangiopericytoma is particularly unusual. However, more than 50% of hemangiopericytoma cases metastasize to the lungs, the bone, and the liver. A long-term clinical and radiological follow up is recommended due to the high risk of recurrence of a potential malignancy. We report a case of a metastatic hemangiopericytoma in the lung that had initially developed in the thigh of a 53 year-old woman 6 years ago. The authors emphasize the long-term follow-up of this type of rare sarcoma.

Intraocular tumors are uncommon and an intraocular metastatic carcinoma is extremely rare. An intraocular metastasis in adults most often originates from the breast or the lung. An intraocular lesion may be the first presentation of cancer and a search should be made to locate the primary tumor. To our knowledge, an intraocular metastasis of a bronchioloaveolar carcinoma has not reported in Korea. We report a case of a bronchioloalveolar carcinoma presenting with the initial symptom of a unilateral visual disturbance due to an intraocular metastasis.

Background : Primary adenoid cystic carcinoma arising in the bronchus is an uncommon disease that is histologically and ultrastructurally identical to the salivary gland tumor of the same name and regarded as a slow growing low-grade malignancy. We examined its clinical characteristics. Method : We collected 13 Korean cases of primary adenoid cystic carcinoma arising in the bronchus including 5 cases of our own and 8 cases from the literature. Result : The patients ages ranged from 20 to 74. Men numbered 9 and women 4. The presenting symptoms were cough, dyspnea, and hemoptysis. The fiberoptic bronchoscopic findings were primarily hypervascular polypoid mass with a smooth surface that obstructed airway totally or near totally. There were three inoperable cases including two cases with distant metastasis to bone or cervical lymph node and one case with mediastinal invasion. The remaining 10 patients underwent surgical resection. Among them, two patients received postoperative radiotherapy. The median survival was 21 months in the 8 surgical and evaluable cases. One patient lived 13 years without recurrence. The prognosis was relatively favorable in operable cases. Conclusion : It was not common for primary adenoid cystic carcinoma arising in the bronchus to have distant metastasis or invasion to the mediastinum on presentation. The prognosis was relatively favorable in operable cases. It would be important to perform flexible bronchoscopy for early diagnosis and to do surgical treatment if possible.

Acute respiratory distress syndrome (ARDS) has been reported to be associated with a variety of medical and surgical conditions, including All-trans-retinoic acid (ATTA). ATRA is very efficaceous drug to acute promyelocytic leukemia (APL). This drug can induce complete remission at APL without fatal risk of disseminated intravascular coagulation. But ATRA treatment, sometimes, produces the symptoms of fever, weight gain and acute respiratory distress, renal function impairment. The causes of these symptoms are not fully proved, but supposed as the result of leukostasis and capillary leak syndrome from excessive leukocyte differentiation and cytokines release. Recently, we experienced a 24-year-old woman who complained gum bleeding for 6 days. At bone marrow biopsy, she was diagnosed as APL. 2 days after ATRA treatment, she was suffered from the symptoms of dyspnea and general ache. At laboratory examination, total leukocyte count was 50,400/, was 42.5 mm Hg and chest PA revealed the findings compatible with ARDS. Treatment with low dose ara-C, corticosteroid and general supportive cares were tried. Within 3 days after treatment, the patient recovered from ARDS by evidence of arterial blood gas study and chest radiographs. She has acquired complete remission of APL with maintenance of A TRA. And so, we present this case with a review of related literatures.