Factors that Predict Clinical Benefit of EGFR TKI Therapy in Patients with EGFR Wild-Type Lung Adenocarcinoma / 결핵및호흡기질환

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR. METHODS: We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. RESULTS: The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH-positive, and 11 were EGFR SISH-negative, with no significant difference in tumor response and survival between EGFR SISH-positive and -negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1 were independent predictors of PFS. ECOG PS 0–1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. CONCLUSION: Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.

Multifocal nodular lymphoid hyperplasia of the lung / 영남의대학술지

Nodular lymphoid hyperplasia (NLH) is a benign lymphoproliferative disease that can affect the lung. Because of its rarity, little is known about the etiology and natural history of NLH. Most cases are usually asymptomatic and found incidentally on imaging studies. Imaging finding of NLH has shown most commonly as a solitary lesion, although multifocal pulmonary nodules may be seen. Surgical resection has proved curative in the cases previously described. We report a rare case of NLH in a 55 year-old man who presented with bilateral multiple pulmonary nodules on chest radiography. Open biopsy was performed from the upper and lower lobe of the left lung. The lesions were pathologically diagnosed as pulmonary NLH. Multifocal residual nodules in both lungs remain stable without spontaneous regression during the 3 years of follow-up.

Multifocal nodular lymphoid hyperplasia of the lung / 영남의대학술지

Nodular lymphoid hyperplasia (NLH) is a benign lymphoproliferative disease that can affect the lung. Because of its rarity, little is known about the etiology and natural history of NLH. Most cases are usually asymptomatic and found incidentally on imaging studies. Imaging finding of NLH has shown most commonly as a solitary lesion, although multifocal pulmonary nodules may be seen. Surgical resection has proved curative in the cases previously described. We report a rare case of NLH in a 55 year-old man who presented with bilateral multiple pulmonary nodules on chest radiography. Open biopsy was performed from the upper and lower lobe of the left lung. The lesions were pathologically diagnosed as pulmonary NLH. Multifocal residual nodules in both lungs remain stable without spontaneous regression during the 3 years of follow-up.

Anti-tuberculosis Treatment-Induced Insulin Autoimmune Syndrome / 이화의대지

Insulin autoimmune syndrome, a rare cause of endogenous hyperinsulinemic hypoglycemia, is characterized by insulin autoantibody, hyperinsulinemia and fasting hypoglycemia. It is well known that drugs containing a sulfhydryl group such as methimazole or α-mercaptopropionyl glycine can induce insulin autoimmune syndrome. However, insulin autoimmune syndrome caused by anti-tuberculosis treatment is very rare. We report a case of insulin autoimmune syndrome after anti-tuberculosis treatment with a review of the relevant literature.

A Case of Kikuchi Disease Involving an Intrapulmonary Lymph Node Mistaken for a Pulmonary Nodule / 대한내과학회지

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is an uncommon idiopathic, self-limiting disease characterized by cervical lymphadenopathy. Patients with KFD may present with a wide variety of nonspecific symptoms, including fever, night sweats, and weight loss. Although KFD can affect all lymph nodes of the body, involvement of the intrathoracic lymph nodes is relatively rare. In particular, isolated involvement of the intrapulmonary lymph nodes is extremely unusual. We herein report a case involving a 45-year-old man who presented with symptoms of myalgia, fatigue, and fever. Computed tomography performed during follow-up showed a slowly growing nodule in the upper lobe of the left lung. Results of laboratory tests did not reveal any evidence of infection or autoimmune disease, including systemic lupus erythematosus. Results of excisional biopsy by video-assisted thoracoscopic surgery revealed KFD in an intrapulmonary lymph node. His symptoms improved after a trial of nonsteroidal anti-inflammatory drugs.

Autophagy Inhibition with Monensin Enhances Cell Cycle Arrest and Apoptosis Induced by mTOR or Epidermal Growth Factor Receptor Inhibitors in Lung Cancer Cells / 결핵및호흡기질환

BACKGROUND: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. METHODS: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. RESULTS: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-G1 phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. CONCLUSION: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

Druggable Targets of Squamous Cell Lung Cancer / 결핵및호흡기질환

Knowledge of molecular pathogenesis of non-small cell lung cancer has increased remarkably and changed the principles of treatment, especially during the past decade. These advancements have been limited mainly to adenocarcinoma of the lung. Recently, genetic alterations in squamous cell lung cancer (SQCLC) have been detailed and positive results of clinical trials using agents targeting these changes have indicated the potential for improved treatment outcomes for SQCLC.

A Case of Recurrent Pulmonary Inflammatory Myofibroblastic Tumor with Aggressive Metastasis after Complete Resection / 결핵및호흡기질환

An inflammatory myofibroblastic tumor (IMT) is a rare disease entity reported to arise in various organs. It is thought to be a neoplastic or reactive inflammatory condition, controversially. The treatment of choice for myofibroblastic tumor is surgery, and recurrence is known to be rare. The optimal treatment method is not well-known for patients ineligible for surgery. We report a 47-year-old patient with aggressive recurrent IMT of the lungs. The patient had been admitted for an evaluation of back-pain two years after a complete resection of pulmonary IMT. Radiation therapy was performed for multiple bone recurrences, and the symptoms were improved. However the patient presented again with aggravated back-pain six months later. High-dose steroid and non-steroidal anti-inflammatory drugs were administered, but the disease progressed aggressively, resulting in spinal cord compression and metastasis to intra-abdominal organs. This is a very rare case of aggressively recurrent pulmonary IMT with multi-organ metastasis.

Endobronchial Mycobacterium avium Infection in an Immunocompetent Patient

Although Mycobacterium avium complex (MAC) is the most common pathogen in nontuberculous mycobacterial (NTM) pulmonary diseases, endobronchial lesions caused by MAC infections are very rare even in an immunocompromised host. Herein, we describe the case of a 59-year-old, HIV-negative and non-immunocompromised woman who developed multifocal pulmonary infiltrations with endobronchial lesion caused by M. avium. Bronchoscopic examination revealed white- and yellow-colored irregular mucosal lesions in the bronchus of the left lingular division. M. avium was identified using sputum culture and bronchial washing fluid culture. Following the recommendations of the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA), the patient was begun on treatment with antimycobacterial drugs. After treatment, pneumonic infiltration decreased.

Dual Inhibition of PI3K/Akt/mTOR Pathway and Role of Autophagy in Non-Small Cell Lung Cancer Cells / 결핵및호흡기질환

BACKGROUND: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects. We have also examined the role of autophagy during this process. METHODS: We analyzed the combination effect of the mTOR inhibitor, temsirolimus, and the Akt inhibitor, GSK690693, on the survival of NCI-H460 and A549 non-small cell lung cancer cells. Cell proliferation was determined by MTT assay and apoptosis induction was evaluated by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Autophagy induction was also evaluated by acridine orange staining. Changes of apoptosis or autophagy-related proteins were evaluated by western blot analysis. RESULTS: Combination treatment with temsirolimus and GSK690693 caused synergistically increased cell death in NCI-H460 and A549 cells. This was attributable to increased induction of apoptosis. Caspase 3 activation and poly(ADP-ribose) polymerase cleavage accompanied these findings. Autophagy also increased and inhibition of autophagy resulted in increased cell death, suggesting its cytoprotective role during this process. CONCLUSION: Taken together, our results suggest that the combination of temsirolimus and GSK690693 could be a novel strategy for lung cancer therapy. Inhibition of autophagy could also be a promising method of enhancing the combination effect of these drugs.

Cutaneous Metastasis from Lung Cancer: A Single-Institution Retrospective Analysis / 결핵및호흡기질환

BACKGROUND: Lung cancer is responsible for substantial proportions of cutaneous metastasis from internal malignancies. The aim of this study was to evaluate the clinical manifestations and outcomes of cutaneous metastasis in Korean lung cancer patients. METHODS: On a retrospective basis, we analyzed medical records of all patients diagnosed with lung cancer from 2000 to 2006. RESULTS: Cutaneous metastases were found in 10 of 4,385 patients. The number of cases was highest for squamous cell carcinoma. However, there was no metastasis from 754 cases of small cell carcinomas. Cutaneous metastasis was detected during staging work-up in 4 patients and it was the presenting sign of recurrence post-operative in 2 patients. Average time from the diagnosis to discovery of cutaneous metastasis was 16.3 months and median survival was 8.5 months (range, 1.8~19.1 months). CONCLUSION: Physicians should be acquainted with clinical manifestations and outcomes of cutaneous metastasis from lung cancer to detect new, recurrent cancer, or disease progression, and to administer appropriate and prompt management.

Enhanced Sensitivity to Gefitinib after Radiation in Non-Small Cell Lung Cancer Cells / 결핵및호흡기질환

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. METHODS: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. RESULTS: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. CONCLUSION: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.

A Case of Nodular Muscular Sarcoidosis Mimicking a Tumor / 대한내과학회지

The nodular form of muscular sarcoidosis is a rare malady that is often confused with a soft-tissue neoplasm or other lesion. Here, we present a case of nodular muscular sarcoidosis in the arms and legs of a 59-year-old woman. She presented at our hospital with a painless nodule in her left arm. Excision was performed and she was diagnosed with sarcoidosis. One year later, nodular sarcoidosis recurred in her arms and legs. After 2 months of steroid medication, the nodules disappeared. The patient has been followed for 2 years and no evidence of recurrence has been observed.

Solitary Pulmonary Metastasis of a Thyroid Papillary Microcarcinoma, Masquerading as Primary Lung Cancer

Although pulmonary metastasis of thyroid cancer is not uncommon, it mostly occurs as multiple discrete nodules on the lung parenchyma. Because thyroid cancer presenting with an isolated large lung mass is extremely rare and the diagnosis is frequently based on small pieces of tissue obtained by a fine needle, the wrong diagnosis such as lung cancer is prone to be made. A 60-year-old man was admitted for evaluation of a lung mass detected on chest radiography. Cytological examination of the bronchial washing specimens suggested adenocarcinoma. Surgery for early lung cancer was performed considering that no other abnormalities were found during the work-up that included 18-fludeoxyglucose positron emission tomography computer tomography (18FDG-PET/CT). Unexpectedly, the diagnosis of papillary thyroid cancer with lung metastasis was made, which prompted us to evaluate the thyroid gland and then remove the primary cancer by subsequent operation. Although it is uncommon, physician should be aware of this possibility, which could help to avoid the wrong diagnosis. Here we report on a typical case of solitary pulmonary metastasis of thyroid cancer and we summarize the previously reported cases with a review of the relevant literature.

Diffuse Alveolar Hemorrhage Subsequently Developed after Recovery from Severe Acute Lung Injury Caused by H1N1 Influenza Infection: A Case Report / 대한구급학회지

Severe acute lung injury (ALI), leading to respiratory failure caused by H1N1 infection, developed in a 34-year-old man during a work-up for non-small cell lung cancer. Although he fully recovered through instant treatment with oseltamivir, mechanical ventilation was required again, 7 days later, due to subsequent diffuse alveolar hemorrhage (DAH). Finally, his condition improved and he was able to move out of the intensive care unit. However, multiple pulmonary metastatic nodules appeared over a period of one month, suggesting the aggressive nature of lung cancer. Although he was discharged after chemotherapy, his prognosis seemed poor, considering the rapidity of growth of the lung cancer. It is important to recognize that DAH can occur after acute lung injury caused by influenza virus.

Prostatic Cancer Presenting as an Isolated Large Lung Mass / 결핵및호흡기질환

A hidden primary tumor presenting as an isolated lung mass is a diagnostic challenge to physicians because the diagnosis of lung cancer is likely to be made if the histologic findings are not inconsistent with lung cancer. A large lung mass was found incidentally in a 59-year-old man. Although adenocarcinoma was diagnosed by percutaneous needle biopsy, thyroid transcription factor-1 (TTF-1) immunostaining was negative, raising suspicion that there was another primary site. There was no abnormal finding except for the lung mass on a 18FDG-PET/CT scan and the patient did not complain of any discomfort. Finally, prostatic cancer was confirmed through the study of tumor markers and prostate-specific antigen (PSA) immunostaining. Because of the rare presentation of a single lung mass in malignancies that have another primary site, physicians should carefully review all data before making a final diagnosis of lung cancer.

Cavernous Sinus Metastasis of Non-Small Cell Lung Cancer / 결핵및호흡기질환

Progressive ptosis and headache developed in a 50-year-old woman with non-small cell lung cancer. Although brain magnetic resonance imaging showed improved cerebellar metastasis after prior radiotherapy without any other abnormality, the follow-up examination taken 6 months later revealed metastasis to the cavernous sinus. The diagnosis of metastasis to the cavernous sinus is often difficult because it is a very rare manifestation of lung cancer, and symptoms can occur prior to developing a radiologically detectable lesion. Therefore, when a strong clinical suspicion of cavernous sinus metastasis exists, thorough neurologic examination and serial brain imaging should be followed up to avoid overlooking the lesion.

Pulmonary actinomycosis requiring surgical resection / 대한내과학회지

No abstract available.

Subcutaneous nodule developed after needle biopsy for lung cancer / 대한내과학회지

No abstract available.

A Large Intrathoracic Meningocele in a Patient with Neurofibromatosis-1

A large intrathoracic meningocele, a saccular protrusion of the meninges through a dilated intervertebral foramen or a bony defect of the vertebral column, was diagnosed in a 41-year-old female patient showing clinical features of neurofibromatosis-1 (NF-1), including cafe-au-lait spots, cutaneous neurofibromas, and axillary frecklings and Lisch nodules on the iris. Her daughter and son also had similar manifestations of NF-1. Regular follow-up with periodic imaging was recommended without surgical treatment because there were no signs or symptoms. Meningocele should be differentiated from posterior mediastinal tumors such as neurofibroma, neuroblastoma, and ganglioneuroma because NF-1 has a high risk of tumor formation. We report on this case with a brief review of the literature.