The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers

Background/Aims@#Genome wide and candidate gene association studies have identified polymorphisms associated with the risk of lung cancer in never-smokers. This study was conducted to evaluate the association between 11 polymorphisms identified in female never smokers and the lung cancer risk in male smokers. @*Methods@#This study included 714 lung cancer patients and 626 healthy controls. The polymorphisms were genotyped using SEQUENOM MassARRAY iPLEX assay or Taq-Man assay. @*Results@#Two polymorphisms were associated with the risk of lung cancer in male smokers, as in female never smokers. Male smokers carrying the rs4975616 variant allele had a significantly decreased risk of lung cancer (in a codominant model: odds ratio, 0.77; 95% confidence interval, 0.61 to 0.96; p = 0.02). The rs9387478 polymorphism also reduced lung cancer risk in male smokers (in a codominant model: odds ratio, 0.85; 95% confidence interval, 0.73 to 0.997; p = 0.046). In a stratified analysis, the association between these polymorphisms and the risk of lung cancer was predominant in lighter smokers and for cases of adenocarcinoma. @*Conclusions@#These results suggest that a subset of polymorphisms known to be associated with the risk of lung cancer in female never smokers is also associated with the risk of lung cancer in male smokers.

Poor Prognostic Factors in Surgically Resected Stage I Non-small Cell Lung Cancer: Histopathologic and Immunohistochemical Analysis

BACKGROUND: A better understanding of the histopathology and molecular biology of lung cancer might improve our capability to predict the outcome for any individual patient. The purpose of this study was to evaluate several histopathologic and molecular markers in order to assess their prognostic value in stage I non-small cell lung cancer. MATERIALS AND METHODS: One hundred ten patients at the Kyungpook National University Hospital were enrolled in the study. Histopathologic factors and molecular markers were selected. RESULTS: Univariate analysis showed that the T stage, differentiation, visceral pleural invasion, and survivin expression were significantly associated with recurrence. Multivariate analysis demonstrated that differentiation and survivin overexpression emerged as independent prognostic factors of recurrence. CONCLUSION: In resected stage I non-small cell lung cancer, poor differentiation and survivin overexpression have been identified as independent predictors of poor disease-free survival.

EML4-ALK Fusion Gene in Korean Non-Small Cell Lung Cancer

A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) has been identified in non-small cell lung cancers (NSCLCs). Although a few studies have evaluated EML4-ALK fusion genes in Korean NSCLCs, the prevalence of different EML4-ALK fusion variants has yet to be clearly assessed. Herein, we have examined the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLCs. EML4-ALK fusion genes have been detected in 10 (6.0%) of 167 patients of NSCLCs and in 9 (7.4%) of 121 patients of adenocarcinoma. Of the 10 patients with fusion genes identified, 8 (80%) were E13;A20 (variant 1) and 2 (20%) were E6;A20, with an additional 33-bp sequence derived from intron 6 of EML4 (variant 3b). These results indicate that the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLC may differ from those in other ethnic populations. Herein, we describe for the first time the profiles of EML4-ALK fusion variants of Korean patients with NSCLCs.

Polymorphisms in Apoptosis-Related Genes and TP53 Mutations in Non-Small Cell Lung Cancer

Apoptosis plays an essential role in the elimination of mutated or transformed cells from the body. Therefore, polymorphisms of apoptosis-related genes may lead to an alteration in apoptotic capacity, thereby affecting the occurrence of TP53 mutations in lung cancer. We investigated the relationship between potentially functional polymorphisms of apoptosis-related genes and TP53 mutations in non-small cell lung cancer (NSCLC). Twenty-seven single nucleotide polymorphisms in 20 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay in 173 NSCLCs and the associations with TP53 mutations in the entire coding exons (exons 2-11), including splicing sites of the gene, were analyzed. None of the 27 polymorphisms was significantly associated with the occurrence of TP53 mutations. This suggests that apoptosis-related genes may not play an important role in the occurrence of TP53 mutations in lung cancer.

TP53 Mutations in Korean Patients with Non-small Cell Lung Cancer

Although TP53 mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, TP53 mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. TP53 mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, P<0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, P=0.01). Our study provides clinical and molecular characteristics of TP53 mutations in Korean patients with NSCLCs.

The Prognostic Factors of Traumatic Diaphragmatic Rupture / 대한흉부외과학회지

BACKGROUND: Traumatic diaphragmatic rupture is not common, but it requires swiftly performing an emergency operation. This study was conducted to evaluate the prognostic factors for mortality after surgically treating traumatic diaphragmatic rupture. MATERIAL AND METHOD: From Jan 2001 to Dec. 2008, we experienced 37 cases of multiple traumas with diaphragmatic injuries that were confirmed by surgical procedures. We evaluated various factors, including the type of injury, the associated injuries, the preoperative vital signs, the ISS, the time until surgery and the rupture size. RESULT: There were 30 patients with blunt trauma and 7 patients with penetrating trauma. Thirty-four patients had associated injuries and the mean ISS was 20.8. Postoperative complications occurred in 11 patients and hospital mortalities occurred in 6 patients. The prognostic factors that had an influence on the postoperative mortalities were the preoperative intubation state, the patient who exhibited hypotension and a high ISS. CONCLUSION: Traumatic diaphragmatic rupture is just one part of multiple traumas. The postoperative mortalities might depend on not only on the diaphragmatic rupture itself, but also on the severity of the associated injuries.

Diagnostic Methods of Traumatic Tracheobronchial Injury / 대한흉부외과학회지

BACKGROUND: The aim of this study was to identify the distinguishing clinicoradiologic findings of traumatic tracheobronchial injury. MATERIAL AND METHOD: Between January 2003 and December 2009, six patients who underwent surgical repair for traumatic tracheobronchial injury due to blunt trauma were included in this study. We evaluated the mechanism of the injury, the coexisting injuries, the time until the making diagnosis and treatment, the diagnostic methods, the anatomic location of the injury and the surgical outcomes. RESULT: The mechanisms of injury were traffic accident and crushing forces. The frequent symptoms were subcutaneous emphysema, dyspnea and pain, and the common radiologic findings were pneumothorax, mediastinal emphysema, rib fracture and lung contusion. Only 2 patients were diagnosed by chest CT and the others were not diagnosed preoperatively. The location of injury was the trachea in 2 patients and the bronchial tree in 4 patients. There was no postoperative mortality or anastomotic leak; however, vocal cord palsy occurred in one patient. The most distinguishing sign was persistent lung collapse even though the chest tube was connected with negative pressure. CONCLUSION: Although it was not easy to diagnose traumatic tracheobronchial injury without a clinical suspicion, the distinguishing clinical symptoms and CT findings could help to make an early diagnosis without performing bronchoscopy.

The Ability of FDG Uptake Ratio and Glut-1 Expression to Predict Mediastinal Lymph Node Metastasis in Resected Non-small Cell Lung Cancer / 대한흉부외과학회지

BACKGROUND: This study was designed to evaluate the FDG uptake ratio of mediastinal node and primary tumors using integrated PET/CT imaging combined with Glut-1 expression of the primary tumor in order to predict the N2 status more accurately in NSCLC patients. MATERIAL AND METHOD: Patients who underwent integrated PET/CT scanning with a detectable mSUV for both primary tumors and mediastinal lymph nodes were eligible for this study. The FDG uptake ratio between the mediastinal node and the primary tumor was calculated. RESULT: The average mSUV of primary tumors and mediastinal nodes were, respectively, 7.4+/-2.2 and 4.2+/-2.2 in N2-positive patients and 7.6+/-3.7 and 2.8+/-6.9 in N2-negative patients. The mean FDG uptake ratio of mediastinal node to primary tumor were 0.58+/-0.23 for malignant N2 lymph nodes and 0.45+/-0.20 for benign lymph nodes (p<0.05). Models which combined Glut-1 expression with an FDG ratio have better diagnostic power than models that use the FDG uptake ratio alone. CONCLUSION: In some patients with a previous history of pulmonary tuberculosis or other inflammatory lung diseases, an FDG uptake ratio combined with Glut-1 expression may be useful in diagnosing mediastinal node metastasis more exactly.

Solitary Plasmacytoma of the Rib: A case report / 대한흉부외과학회지

Solitary plasmacytoma of bone is a rare disease that accounts for only about 3~5% of all plasma cell tumors. Especially, no case of solitary plasmacytoma of a rib origin has been described in the Korean literature. A 54 year old Korean man was referred to our hospital for further evaluation of a lung mass that had been detected on a screening chest radiograph. A tumor with a left 6th rib origin was revealed by the computed tomography (CT) and positive emission tomography (PET-CT); therefore, surgical resection was performed. The histopathological findings of the tumor revealed plasmacytoma of a rib origin. The postoperative screening test revealed no evidence of multiple myeloma. Postoperative radiation therapy was not performed, and no new lesion has been noted during the 2 years of follow up.

Intrapericardial Pericardial Cyst / 대한흉부외과학회지

Pericardial cyst is an uncommon congenital mediastinal tumor. The majority of pericardial cysts are located in the right cardiophrenic angle, but rarely they can be located intrapericardially. We now present a case of a huge intrapericardial pericardial cyst excised with video-assisted thoracoscopic surgery.

Identification of Tumor Suppressor Genes on Chromosome 21 / 대한흉부외과학회지

BACKGROUND: We performed this study to identify the tumor suppressor genes located in the long arm of chromosome 21 in non-small cell lung cancer. MATERIAL AND METHOD: The genes of USP25 in 21q11.2, NCAM2, ADAMTS1 in 21q21.2, and Claudin-8 (CLDN8), Claudin-17 (CLDN17) and TIAM1 in 21q22.1 were investigated for their gene expressions, genetic alterations and promoter methylation. RESULT: The expressions of CLDN8 and CLDN17 were significantly decreased in 7 (L132, H157, H358, H522, H1299, H1703 and HCC2108) of 13 cell lines, and the expression of ADAMTS1 was also significantly reduced in 6 cell lines (A549, SW900, H1299, H1373, H1703 and H1793). There were no genetic alterations by PCR-SSCP and cDNA cloning in the cell lines with a decreased gene. In the cell lines with a decreased gene expression, the mRNA expression was increased significantly with treatment of 5-Aza-CdR. CONCLUSION: These results suggest that the ADMTS1, CLDN8 and CLDN17 may act as tumor suppressor genes.

The Differences between Ruptured and Unruptured Mediastinal Teratoma / 대한흉부외과학회지

BACKGROUND: Benign teratoma is mostly asymptomatic, but this tumor rarely ruptures into the adjacent structure such as the pleural space, pericardium, lung parenchyma or tracheobronchial tree. Thus, it is important to differentiate ruptured teratoma from unruptured teratoma. This study evaluated the difference between ruptured and unruptured benign teratoma. MATERIAL AND METHOD: Twenty-four cases of surgically resected benign teratomas were reviewed retrospectively. The clinical symptoms, chest CT findings and operative findings of the ruptured teratoma were compared with those of the unruptured teratoma. Especially, the tumor size, wall thickness, location of the mass, internal septation, homogeneity, calcification and ancillary findings were evaluated on CT. RESULT: Of the 24 patients, 7 patients were diagnosed with ruptured teratoma. Severe symptoms were more commonly found for ruptured teratoma than for unruptured teratoma. The ruptured teratoma had a tendency to display calcification and such ancillary findings as collapse or consolidation of the lung parenchyma. For the ruptured teratoma, the resection was performed by sternotomy or thoracotomy, and more lung resection was included. CONCLUSION: Calcification within the mass and changes in the lung parenchyma on the preoperative CT findings can be diagnostic signs of a ruptured teratoma. The demonstration of ruptured teratoma is important not only for making the early diagnosis, but also for the surgical planning.

Definitive Chemoradiotherapy with Capecitabine and Cisplatin in Patients with Esophageal Cancer: A Pilot Study

We aimed to evaluate the feasibility of concurrent chemoradiotherapy (CRT) with capecitabine and cisplatin in patients with squamous cell carcinoma of the esophagus. Eighteen patients with esophageal cancer were enrolled on the study. The chemotherapy during CRT consisted of two cycles of intravenous cisplatin of 60 mg/ m2 on day 1 and oral capecitabine 825 mg/m2 twice daily from day 1 to 14 at 3-week intervals. The radiotherapy (2.0 Gy fraction/day to a total dose of 60 Gy) was delivered to the primary tumor site and regional lymph node. After concurrent CRT, 2 cycles of capecitabine (1,000 mg/m2 b.i.d from days 1 to 14) plus cisplatin (60 mg/m2 on day 1) were added every 3 weeks. All patients completed the planned treatment. After the chemoradiotherapy, 12 complete responses (CR, 66.7%) and 6 partial responses (PR, 33.3%) were confirmed. Grade 3 or 4 neutropenia only occurred in 2 patients, plus no treatment-related death was observed. At a median follow-up duration of 14.9 months, the estimated overall survival and progression-free survival rate at 2-yr was 70.7% and 54.4%, respectively. Concurrent CRT with capecitabine and cisplatin was found to be well-tolerated and effective in patients with esophageal cancer.

Chest Wall Tuberculosis: Clinical Features and Treatment Outcomes / 결핵및호흡기질환

BACKGROUND: A diagnosis and treatment of chest wall tuberculosis (CWTB) is both difficult and controversial. The aim of this study was to collect information on the optimal treatment for CWTB. METHODS: The clinical features, radiographic findings, and treatment outcomes of 26 patients, who underwent surgery and were diagnosed histopathologically, were retrospectively analyzed. RESULTS: The most common presenting symptom was a palpable mass found in 24 patients (92.3%). In all patients, CT revealed a soft tissue mass that was accompanied by a central low density, with or without peripheral rim enhancement. The sensitivity and specificity of the bone scintigram for bone involvement were 87.5% and 100%, respectively. CWTB was diagnosed preoperatively by aspiration cytology and smear for acid-fast bacilli in five out of 11 patients. Twenty-three patients (88.5%) underwent a radical excision and three underwent incision/drainage or an incisional biopsy. The duration of antituberculous medication was 7.5+/-3.98 months with a follow-up period of 28.2+/-26.74 months. Among the 20 patients who completed their treatment, nine received chemotherapy for six months or less and 11 received chemotherapy for nine months or more. Two patients had a recurrence four and seven months after starting their medication. CONCLUSION: A 6 month regimen may be appropriate for CWTB patients who have undergone a complete excision.

Spontaneous Pneumomediastinum Accompanied by Bleomycin-Induced Lung Toxicity / 대한흉부외과학회지

Pneumomediastinum is a rare, but well recognized complication of bleomycin-induced lung toxicity. Spontaneous pneumomediastinum has to be considered as one of the causes when the dyspnea becomes aggravated in patients with bleomycin induced lung toxicity. We describe here two patients who suffered with germ cell tumor and they developed spontaneous pneumomediastinum without pneumothorax, and this was caused by bleomycin-induced lung toxicity.

Clinical Outcome of Pulmonary Metastasectomy in Patients with Pulmonary Metastasis / 대한흉부외과학회지

BACKGROUND: Surgical resection is accepted widely as the standard therapy for complete resectable pulmonary metastases. The number of cases of pulmonary metastasectomy and its survival rate is increasing due to the development of the therapeutic modalities. We attempted to analyze the survival rate and prognosis factors of pulmonary metastasectomy during the last 10 years. MATERIAL AND METHOD: We retrospectively analyzed the data of 89 patients who underwent 96 procedures of pulmonary metastasectomy between January 1996 and December 2005. The factors that may influence the long term prognosis such as completeness of resection, the type of primary cancer, the disease-free interval, the number and size of metastasis and the laterality were investigated. RESULT: There was no operative mortality. The mean disease free interval (DFI) was 29.6+/-27.9 months and there were 3 cases of synchronous metastasis (3.4%). The overall 3, 5 and 10 year survival rate was 52.5%, 32.1% and 20.7%, respectively. The median survival time was 38 months. The 5-year survival rate according to the IRLM appraisal was 63.5%, 33.3%, 22.1% and 0% for stage I, II, III and IV, respectively. Univariate analysis showed a better prognosis for patients with a disease free interval of 36 months or more, unilateral metastasis and 4 or less metastases. CONCLUSION: The survival rate for completely resectable pulmonary metastasectomy was favorable. The disease free interval, laterality and the number of metastasis were the prognosis factors.

Risk Factor for Recurrence in Completely Resected Stage IB Non-small Cell Lung Cancer / 대한흉부외과학회지

BACKGROUND: Complete surgical resection is the most effective treatment for stage IB non-small cell lung cancer (NSCLC). Recurrence accounts for the disappointing survival rates after resection. There has been renewed interest in adjuvant therapy after complete resection. Appropriate selection of effective adjuvant therapy will depend on the prognostic factors for recurrence. MATERIAL AND METHOD: The study included 114 patients with completely resected stage IB NSCLC. The variables selected for the study were gender, age, the type of resection, cell type, the degree of differentiation, the tumor size and the presence of visceral pleura invasion. The Kaplan-Meier method was used to estimate the survival and disease-free survival rate. The results were compared using the log rank test. Multivariate analysis was performed by Cox's proportional hazard model. Two-sided p-valves <0.05 were considered to be statistically significant. RESULT: The 3-year overall survival and the disease-free survival rates were 87.0% and 79.4%, respectively. The degree of differentiation showed a significant influence on disease-free survival according to the univariate analysis. According to the multivariate analysis, a poor grade of differentiation was a significant poor prognostic factor. CONCLUSION: These results demonstrate that poor differentiation may be a poor prognostic factor for patients with completely resected IB NSCLC. Therefore, the patients with a poor grade of differentiation may require adjuvant therapies.

Metastatic Pulmonary Hemangiopericytoma from Retroperitoneum: A case report / 대한흉부외과학회지

Hemangiopericytoma is a rare vascular tumor derived from the pericyte and usually occures in the lower extremities and the retroperitoneum. Complete excision is treatment of choice. Regular follow up is strongly recommended due to its potential malignancy which is recurrence and metastasis. We experienced surgical excision of metastatic pulmonary hemangiopericytoma from retroperitoneal hemangiopericytoma completely excised 10 years ago.

Primary Malignant Melanoma of Lung : A case report / 대한흉부외과학회지

malignant melanoma of the lung is extremely rare. A 46-year-old lady was admitted with two month history of dry cough and blood-tinged sputum. Chest CT showed 4.5x5.0 cm sized mass at the right lower lobe. Repeated bronchoscopic and percutaneous biopsies showed no definite diagnosis. Preoperative evaluations revealed no systemic metastais. Primary So, we tried the surgical approach. Right lower lobectomy and lymph node dissection was done. The mass and lymph node were confirmed as primary malignant melanoma. The patient presented with right hemiparesis 40 days after operation. Brain MRI showed 1.5x2.0 cm sized mass lesion on the left parietal lobe. Mass excision was done. However, she expired 8 months later.

Clinical Characteristics of Tuberculous Empyema / 결핵및호흡기질환

BACKGROUND: In contrast to tuberculous pleurisy, tuberculous empyema is a chronic active infectious disease of the pleural cavity that is frequently accompanied by cavitary or advanced pulmonary lesions. The condition requires long-term anti-tuberculous medication with external drainage. The clinical features and treatment outcome of tuberculous empyema are unclear despite the high prevalence of tuberculosis in Korea. METHODS: From January 1991 through April 2004, 17 patients diagnosed with tuberculous empyema in Kyungpook National University Hospital were enrolled in this study. Their medical records and chest radiographs were reviewed. RESULTS: Twelve patients(71%) had a history of tuberculosis and six of the 12 patients were under current anti-tuberculous medication. Productive cough, fever, and dyspnea were the main complaints. There was no predominance between the right and left lungs. Nine patients(53%) had far-advanced pulmonary tuberculosis, two(12%) had a cavitary lesion, and seven(41%) had a pyopneumothorax on the chest radiograph. All eight cases in whom the data of pleural fluid WBC differential count was available showed polymorphonuclear leukocyte predominance. Eight patients(47%) had other bacterial infections as well. The overall rates of a positive sputum AFB smear and culture for M. tuberculosis were 71% and 64%, respectively. The positive AFB smear and culture rates for M. tuberculosis from the pleural fluid were 33% and 36%, respectively. Twelve of the 16 patients(75%) were treated successfully. Three underwent additional surgical intervention. Two patients (12%) died during treatment. CONCLUSION: Tuberculous empyema is frequently accompanied by advanced pulmonary lesions, and polymorphonuclear leukocytes are predominant in the pleural fluid. Other accompanying bacterial infections in the pleural cavity are also common in tuberculous empyema patients. Therefore, tuberculous empyema should be considered in differential diagnosis of patients with polymorphonuclear leukocyte-predominant pleural effusion. In addition, more active effort will be needed to achieve a bacteriological diagnosis in the pleural fluid.