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1.  Adrenal lymphangioma masquerading as a pancreatic tail cyst 
World Journal of Gastroenterology : WJG  2014;20(36):13195-13199.
Cystic lymphangiomas of the adrenal gland are rare. A 79-year-old female presented in the emergency room with epigastric discomfort, and an immovable mass was palpated in her abdomen upon physical examination. Imaging studies revealed a large cystic lesion in the pancreatic tail. The radiologic impression ruled out the possibility of a mucinous cystic neoplasm, or a pseudocyst in the pancreas. The operative findings demonstrated that the cystic mass originated in the left adrenal gland. A laparoscopic excision of the cystic mass was performed, and immunohistochemistry confirmed that this mass was a lymphangioma of the adrenal gland. Several prior reports have suggested that lymphangioma can mimic renal or splenic cysts. However, lymphangioma cases mimicking pancreatic cysts are very rare.
doi:10.3748/wjg.v20.i36.13195
PMCID: PMC4177502  PMID: 25278717
Lymphangioma; Adrenal gland; Pancreas; Cyst; Mucinous neoplasm
2.  Astrocyte elevated gene-1 overexpression in hepatocellular carcinoma: an independent prognostic factor 
Purpose
Astrocyte elevated gene-1 (AEG-1) plays important roles in tumorigenesis such as proliferation, invasion, metastasis, angiogenesis, and chemoresistance. We examined the expression of AEG-1 in patients with hepatocellular carcinoma (HCC).
Methods
Eighty-five samples were collected from patients with HCC who underwent surgery and were histopathologically confirmed to have HCC. Two independent pathologists, experienced in evaluating immunohistochemistry and blinded to the clinical outcomes of the patients, reviewed all samples. They determined AEG-1 expression semiquantitatively by assessing the percentage of positively stained immunoreactive cells and staining intensity. Clinicopathological data were analyzed in association with prognosis.
Results
The association was estimated by univariate and multivariate analyses with Cox regression. Tumor size (hazard ratio [HR], 2.285; 95% confidence interval [CI], 1.175-4.447; P = 0.015), microvascular invasion (HR, 6.754; 95% CI, 1.631-27.965; P = 0.008), and AEG-1 expression (HR, 4.756; 95% CI, 1.697-13.329; P = 0.003) were independent prognostic factors for overall survival. Those for disease-free survival rate were tumor size (HR, 2.245; 95% CI, 1.282-3.933; P = 0.005) and AEG-1 expression (HR, 1.916; 95% CI, 1.035-3.545; P = 0.038). The cumulative 5-year survival and recurrence rates were 89.2% and 50.0% in the low-expressing group and 24.5% and 82.4% in the high-expressing group, respectively.
Conclusion
The results suggest that AEG-1 overexpression could serve as a valuable prognostic marker in patients with HCC.
doi:10.4174/astr.2015.88.2.77
PMCID: PMC4325651
Human MTDH protein; Hepatocellular carcinoma; Neoplasm metastasis
3.  Prognostic Value of Serum Growth Differentiation Factor-15 in Patients with Chronic Obstructive Pulmonary Disease Exacerbation 
Background
Information regarding prognostic value of growth differentiation factor 15 (GDF-15) and heart-type fatty acid-binding protein (H-FABP) in patients with chronic obstructive pulmonary disease (COPD) exacerbation is limited. The aim of this study was to investigate whether serum levels of GDF-15 and H-FABP predict an adverse outcome for COPD exacerbation.
Methods
Clinical variables, including serum GDF-15 and H-FABP levels were compared in prospectively enrolled patients with COPD exacerbation that did or did not experience an adverse outcome. An adverse outcome included 30-day mortality and need for endotracheal intubation or inotropic support.
Results
Ninety-seven patients were included and allocated into an adverse outcome (n=10) or a control (n=87) group. Frequencies of mental change and PaCO2>37 mm Hg were significantly higher in the adverse outcome group (mental change: 30% vs. 6%, p=0.034 and PaCO2>37 mm Hg: 80% vs. 22%, p<0.001, respectively). Serum GDF-15 elevation (>1,600 pg/mL) was more common in the adverse outcome group (80% vs. 43%, p=0.041). However, serum H-FABP level and frequency of serum H-FABP elevation (>755 pg/mL) did not differ between the two groups. Multivariate analysis showed that an elevated serum GDF-15 and PaCO2>37 mm Hg were significant predictors of an adverse outcome (odds ratio [OR], 25.8; 95% confidence interval [CI], 2.7-243.8; p=0.005 and OR, 11.8; 95% CI, 1.2-115.3; p=0.034, respectively).
Conclusion
Elevated serum GDF-15 level and PaCO2>37 mm Hg were found to predict an adverse outcome independently in patients with COPD exacerbation, suggesting the possibility that serum GDF-15 could be used as a prognostic biomarker of COPD exacerbation.
doi:10.4046/trd.2014.77.6.243
PMCID: PMC4286781  PMID: 25580140
Pulmonary Disease, Chronic Obstructive; Disease Progression; Growth Differentiation Factor 15; FABP3 Protein, Human
4.  Incidental cholecystojejunal fistula treated with successful laparoscopic management 
Internal biliary fistula (IBF) is occurred spontaneously due to the biliary disease in most cases. Bilioenteric, biliobiliary, bronchobiliary, and vasculobiliary type of IBF have been reported in the literature. We herein describe our experience with an incidental cholecystojejunal fistula, a very rare type of bilioenteric fistula in laparoscopic cholecystectomy. A 61-year-old woman with several years' history of intermittent right upper abdominal pain was admitted to Soonchunhyang University Cheonan Hospital. Abdominal CT scan showed the pneumobilia in gallbladder with common bile duct dilatation. Endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy were done. On operative findings, there was a cholecystojejunal fistula. We performed laparoscopic cholecystectomy and fistulectomy with jejunal partial resection. To our knowledge, this is the first report on incidental cholecystojejunal fistula uncombined with any other disease and was treated with laparoscopic procedure.
doi:10.4174/astr.2014.87.5.276
PMCID: PMC4217258  PMID: 25368855
Cholecystojejunal fistula; Biliary fistula; Gallbladder
5.  Clinical Relevance of Bronchial Anthracofibrosis in Patients with Chronic Obstructive Pulmonary Disease Exacerbation 
Background
Bronchial anthracofibrosis (BAF), which is associated with exposure to biomass smoke in inefficiently ventilated indoor areas, can take the form of obstructive lung disease. Patients with BAF can mimic or present with an exacerbation of chronic obstructive pulmonary disease (COPD). The purpose of the current study was to investigate the prevalence of BAF in Korean patients with COPD exacerbation as well as to examine the clinical features of these patients in order to determine its clinical relevance.
Methods
A total of 206 patients with COPD exacerbation were divided into BAF and non-BAF groups, according to computed tomography findings. We compared both clinical and radiologic variables between the two groups.
Results
Patients with BAF (51 [25%]) were older, with a preponderance of nonsmoking women; moreover, they showed a more frequent association with exposure to wood smoke compared to those without BAF. However, no differences in the severity of illness and clinical course between the two groups were observed. Patients in the BAF group had less severe airflow obstruction, but more common and severe pulmonary hypertension signs than those in the non-BAF group.
Conclusion
Compared with non-BAF COPD, BAF may be associated with milder airflow limitation and more frequent signs of pulmonary hypertension with a more severe grade in patients presenting with COPD exacerbation.
doi:10.4046/trd.2014.77.3.124
PMCID: PMC4192310  PMID: 25309607
Anthracosis; Biomass; Pulmonary Disease, Chronic Obstructive; Tomography, Spiral Computed; Hypertension, Pulmonary
6.  Delayed presentation of cerebellar and spinal cord infarction as a complication of computed tomography-guided transthoracic lung biopsy: a case report 
Introduction
Computed tomography-guided transthoracic needle biopsy is a common diagnostic procedure that is associated with various complications including pneumothorax, parenchymal hemorrhage, and hemoptysis. A systemic air embolism is a very rare (0.06 to 0.21%) but potentially fatal complication.
Case presentation
A 70-year-old Korean male was admitted to our hospital for evaluation of a solitary pulmonary nodule located adjacent to the right inferior pulmonary vein in the medial basal segment of the right lower lobe. A computed tomography-guided needle biopsy was performed by a radiologist using a coaxial needle. A computed tomography image obtained immediately after the biopsy showed intraluminal free air in the proximal ascending aorta. He complained of a mild electrical current sensation in both lower extremities. After three hours he complained of neurological deficit in both lower extremities as well as voiding difficulty. The brain and spine magnetic resonance images showed a right cerebellar and spinal cord infarction at the T8-10 levels.
Conclusions
We report a case of air embolism to the cerebellum and spinal cord causing infarction presenting with an initial symptom of mild electrical current sensation in both lower extremities during the transthoracic needle biopsy. For this potentially fatal complication, early recognition, followed by prompt therapy is critical to reducing morbidity and mortality.
doi:10.1186/1752-1947-8-272
PMCID: PMC4136409  PMID: 25113016
Air embolism; Lung biopsy; Complication
7.  Clinical Utility of CT-Based Bronchial Aspirate TB-PCR for the Rapid Diagnosis of Pleural Tuberculosis 
Background
Thoracoscopic pleural biopsy is often required for rapid and confirmative diagnosis in patients with suspected pleural tuberculosis (PL-TB). However, this method is more invasive and costly than its alternatives. Therefore, we evaluated the clinical utility of the chest computed tomography (CT)-based bronchial aspirate (BA) TB-polymerase chain reaction (PCR) test in such patients.
Methods
Bronchoscopic evaluation was performed in 54 patients with presumptive PL-TB through diagnostic thoracentesis but without a positive result of sputum acid-fast bacilli (AFB) smear, pleural fluid AFB smear, or pleural fluid TB-PCR test. Diagnostic yields of BA were evaluated according to the characteristics of parenchymal lesions on chest CT.
Results
Chest radiograph and CT revealed parenchymal lesions in 25 (46%) and 40 (74%) of 54 patients, respectively. In cases with an absence of parenchymal lesions on chest CT, the bronchoscopic approach had no diagnostic benefit. BA TB-PCR test was positive in 21 out of 22 (95%) patients with early-positive results. Among BA results from 20 (37%) patients with patchy consolidative CT findings, eight (40%) were AFB smear-positive, 18 (90%) were TB-PCR-positive, and 19 (95%) were culture-positive.
Conclusion
The BA TB-PCR test seems to be a satisfactory diagnostic modality in patients with suspected PL-TB and patchy consolidative CT findings. For rapid and confirmative diagnosis in these patients, the bronchoscopic approach with TB-PCR may be preferable to the thoracoscopy.
doi:10.4046/trd.2013.75.4.150
PMCID: PMC3833935  PMID: 24265643
Tuberculosis, Pleural; Bronchoscopy; Polymerase Chain Reaction; Thoracoscopy
8.  Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia 
Hosgood, H. Dean | Wang, Wen-Chang | Hong, Yun-Chul | Wang, Jiu-Cun | Chen, Kexin | Chang, I-Shou | Chen, Chien-Jen | Lu, Daru | Yin, Zhihua | Wu, Chen | Zheng, Wei | Qian, Biyun | Park, Jae Yong | Kim, Yeul Hong | Chatterjee, Nilanjan | Chen, Ying | Chang, Gee-Chen | Hsiao, Chin-Fu | Yeager, Meredith | Tsai, Ying-Huang | Wei, Hu | Kim, Young Tae | Wu, Wei | Zhao, Zhenhong | Chow, Wong-Ho | Zhu, Xiaoling | Lo, Yen-Li | Sung, Sook Whan | Chen, Kuan-Yu | Yuenger, Jeff | Kim, Joo Hyun | Huang, Liming | Chen, Ying-Hsiang | Gao, Yu-Tang | Kim, Jin Hee | Huang, Ming-Shyan | Jung, Tae Hoon | Caporaso, Neil | Zhao, Xueying | Huan, Zhang | Yu, Dianke | Kim, Chang Ho | Su, Wu-Chou | Shu, Xiao-Ou | Kim, In-San | Bassig, Bryan | Chen, Yuh-Min | Cha, Sung Ick | Tan, Wen | Chen, Hongyan | Yang, Tsung-Ying | Sung, Jae Sook | Wang, Chih-Liang | Li, Xuelian | Park, Kyong Hwa | Yu, Chong-Jen | Ryu, Jeong-Seon | Xiang, Yongbing | Hutchinson, Amy | Kim, Jun Suk | Cai, Qiuyin | Landi, Maria Teresa | Lee, Kyoung-Mu | Hung, Jen-Yu | Park, Ju-Yeon | Tucker, Margaret | Lin, Chien-Chung | Ren, Yangwu | Perng, Reury-Perng | Chen, Chih-Yi | Jin, Li | Chen, Kun-Chieh | Li, Yao-Jen | Chiu, Yu-Fang | Tsai, Fang-Yu | Yang, Pan-Chyr | Fraumeni, Joseph F. | Seow, Adeline | Lin, Dongxin | Zhou, Baosen | Chanock, Stephen | Hsiung, Chao Agnes | Rothman, Nathaniel | Lan, Qing
Human genetics  2012;131(7):10.1007/s00439-012-1144-8.
A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10−12); however, this association did not achieve genome-wide significance (p < 10−7) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10−8; allelic risk = 0.80, 95% confidence interval (CI) = 0.74–0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67–0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.
doi:10.1007/s00439-012-1144-8
PMCID: PMC3875137  PMID: 22367405
9.  Diverticular Choledochal Cyst with a Large Impacted Stone Masquerading as Mirizzi's Syndrome 
Case Reports in Gastroenterology  2013;7(1):164-168.
Choledochal cysts are congenital anomalies of the biliary tract manifested by cystic dilatation of the extrahepatic and intrahepatic bile ducts. Choledochal cyst is not rare in far-East Asian countries. Type II choledochal cysts account for 2% of all such cysts. They are true diverticula of the extrahepatic bile duct and communicate with the bile duct through a narrow stalk. This condition is associated with significant complications, such as ductal strictures, stone formation, cholangitis, rupture and secondary biliary cirrhosis. We describe a case of a huge impacted stone in a diverticular choledochal cyst which masqueraded as an unusual cystic duct stone causing Mirizzi's syndrome.
doi:10.1159/000350253
PMCID: PMC3635692  PMID: 23626517
Choledochal cyst; Mirizzi's syndrome; Cholangitis
10.  An Adult Case of Fisher Syndrome Subsequent to Mycoplasma pneumoniae Infection 
Journal of Korean Medical Science  2013;28(1):152-155.
Reported herein is an adult case of Fisher syndrome (FS) that occurred as a complication during the course of community-acquired pneumonia caused by Mycoplasma pneumoniae. A 38-yr-old man who had been treated with antibiotics for serologically proven M. pneumoniae pneumonia presented with a sudden onset of diplopia, ataxic gait, and areflexia. A thorough evaluation including brain imaging, cerebrospinal fluid examination, a nerve conduction study, and detection of serum anti-ganglioside GQ1b antibody titers led to the diagnosis of FS. Antibiotic treatment of the underlying M. pneumoniae pneumonia was maintained without additional immunomodulatory agents. A complete and spontaneous resolution of neurologic abnormalities was observed within 1 month, accompanied by resolution of lung lesions.
doi:10.3346/jkms.2013.28.1.152
PMCID: PMC3546094  PMID: 23341726
Mycoplasma pneumoniae; Fisher Syndrome; Anti-GQ1b Antibody
11.  A Functional Polymorphism in the CHRNA3 Gene and Risk of Chronic Obstructive Pulmonary Disease in a Korean Population 
Journal of Korean Medical Science  2012;27(12):1536-1540.
A genome-wide association study has identified the 15q25 region as being associated with the risk of chronic obstructive pulmonary disease (COPD) in Caucasians. This study intended as a confirmatory assessment of this association in a Korean population. The rs6495309C > T polymorphism in the promoter of nicotinic acetylcholine receptor alpha subunit 3 (CHRNA3) gene was investigated in a case-control study that consisted of 406 patients with COPD and 394 healthy control subjects. The rs6495309 CT or TT genotype was associated with a significantly decreased risk of COPD when compared to the rs6495309 CC genotype (adjusted odds ratio = 0.69, 95% confidence interval = 0.50-0.95, P = 0.023). The effect of the rs6495309C > T on the risk of COPD was more evident in moderate to very severe COPD than in mild COPD under a dominant model for the variant T allele (P = 0.024 for homogeneity). The CHRNA3 rs6495309C > T polymorphism on chromosome 15q25 is associated with the risk of COPD in a Korean population.
doi:10.3346/jkms.2012.27.12.1536
PMCID: PMC3524434  PMID: 23255854
CHRNA3; Pulmonary Disease, Chronic Obstructive; Polymorphism
12.  EML4-ALK Fusion Gene in Korean Non-Small Cell Lung Cancer 
Journal of Korean Medical Science  2012;27(2):228-230.
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.
doi:10.3346/jkms.2012.27.2.228
PMCID: PMC3271302  PMID: 22323876
ALK; EML4; Carcinoma; Non-Small-Cell Lung
13.  Stromal-cell-derived Factor 1-α Promotes Tumor Progression in Colorectal Cancer 
Purpose
Although stromal-cell-derived factor (SDF)-1α is suggested to be involved in tumorigenicity and tumor angiogenesis, the clinicopathological significance of its expression in colorectal cancers is not fully understood. We examined SDF-1α expression in colorectal cancers and investigated its relationship to clinicopathological features such as tumor staging, lymph-node metastasis, vascular invasion (VI), lymphatic invasion (LI) and neural invasion (NI).
Methods
Specimens of 83 primary colorectal cancers were examined immunohistochemically, and the relationships between clinicopathological features and SDF-1α expression were analyzed. To compare the expressions between the normal colon tissue and colorectal cancer tissues, we performed Western blot analyses.
Results
According to the Western blot analyses, SDF-1α was more highly expressed in colorectal carcinoma tissues than in normal colonic mucosa (20/21). According to the immunohistochemical stain, SDF-1α was associated with nodal status, distant metastasis, tumor staging, VI and LI. SDF-1α expression had a significant prognostic value for overall survival. Kaplan-Meier plots of survival in patients with high SDF-1α showed that high SDF-1α expression was associated with a shorter overall survival. However, no association was found between SDF-1α expression and other pathologic or clinical variables, including age, gender, degree of differentiation, and presence of perineural invasion.
Conclusion
The expression of SDF-1α might be associated with tumor progression in colorectal cancer. Inhibition of SDF-1α could be a therapeutic option in colorectal cancer patients.
doi:10.3393/jksc.2012.28.1.27
PMCID: PMC3296938  PMID: 22413079
Colorectal neoplasms; Survival; Prognostic factor; SDF-1α; Chemokine CXCL12
14.  Correlation between Liver Metastases and the Level of PRL-3 mRNA Expression in Patients with Primary Colorectal Cancer 
Purpose
Phosphatase of regenerating liver-3 (PRL-3) has been associated with metastasis promotion. However, clinical applications of this association have not yet been clearly demonstrated. In this study, we evaluated the relation of PRL-3 mRNA level in primary colorectal cancer to the corresponding stage and to other clinicopathologic factors.
Methods
Two hundred forty-five patients with histologically-proven colorectal cancer underwent surgery between January 2004 and December 2006. RNA was extracted and cDNA was prepared by using reverse transcription. Quantification of PRL-3 was done using a real-time polymerase chain reaction.
Results
Eighty-six cases with well-preserved specimens were enrolled: 53 males and 33 females. The mean age was 63.4 years. According to tumour node metastasis (TNM) stage of the American Joint Committee on Cancer (AJCC), stage I was 11 cases, stage II was 38 cases, stage III was 23 cases, and stage IV was 14 cases. Among stage IV cases, one case was combined with liver and lung metastases, and one case was combined with liver metastases and peritoneal dissemination. The remaining stage IV patients were combined with only liver metastases. There was a significant correlation in PRL-3 mRNA expression between primary colorectal cancer and corresponding tumor stage. PRL-3 mRNA expression was increased in the liver metastases cases. Lymphatic and vascular invasion were significantly related with PRL-3 mRNA levels.
Conclusion
Advanced stage prediction may be obtained by measuring the level of PRL-3 mRNA expression in primary colorectal cancer. Especially, the risk of liver metastases may be predicted by measuring the level of PRL-3 mRNA expression in primary colorectal cancer. Further study is required to confirm these preliminary results.
doi:10.3393/jksc.2011.27.5.231
PMCID: PMC3218126  PMID: 22102972
PTP4A3 protein, human; Real-time polymerase chain reaction; Colorectal neoplasms; Neoplasm Metastasis
15.  Drain Tube-Induced Jejunal Penetration Masquerading as Bile Leak following Whipple's Operation 
Case Reports in Gastroenterology  2011;5(2):295-300.
A 70-year-old man had undergone pancreaticoduodenectomy due to a distal common bile duct malignancy. After the operation, serous fluid discharge decreased from two drain tubes in the retroperitoneum. Over four weeks, the appearance of the serous fluid changed to a greenish bile color and the patient persistently drained over 300 ml/day. Viewed as bile leak at the choledochojejunostomy, treatment called for endoscopic diagnosis and therapy. Cap-fitted forward-viewing endoscopy demonstrated that the distal tip of a pancreatic drain catheter inserted at the pancreaticojejunostomy site had penetrated the opposite jejunum wall. One of the drain tubes primarily placed in the retroperitoneum had also penetrated the jejunum wall, with the distal tip positioned near the choledochojejunostomy site. No leak of contrast appeared beyond the jejunum or anastomosis site. Following repositioning of a penetrating catheter of the pancreaticojejunostomy, four days later, the patient underwent removal of two drain tubes without additional complications. In conclusion, the distal tip of the catheter, placed to drain pancreatic juice, penetrated the jejunum wall and may have caused localized perijejunal inflammation. The other drain tube, placed in the retroperitoneal space, might then have penetrated the inflamed wall of the jejunum, allowing persistent bile drainage via the drain tube. The results masqueraded as bile leakage following pancreaticoduodenectomy.
doi:10.1159/000329172
PMCID: PMC3124320  PMID: 21712980
Whipple's operation; Bile leak; Drain tube; Intestinal penetration
16.  Performance of whole-blood interferon-gamma release assay in patients admitted to the emergency department with pulmonary infiltrates 
BMC Infectious Diseases  2011;11:107.
Background
This study was conducted to evaluate the performance of a whole-blood interferon-gamma release assay in inpatients who were admitted to the emergency department (ED) with pulmonary infiltrates who required a differential diagnosis with pulmonary tuberculosis (TB).
Methods
The patients with pulmonary infiltrates who received a QuantiFERON (QFT) test in the ED were included as an inpatient group and were divided into TB and non-TB group based on the final diagnosis. Patients with pulmonary TB who were tested in the outpatient department served as a control group.
Results
In total, 377 QFT tests were analyzed. Of the 284 inpatient QFT tests, 29.6% had an indeterminate result (35.2% in the 196 patients with non-TB and 17.0% in the 88 patients with TB). In contrast, only 1.1% of the 93 outpatients with TB returned an indeterminate result (p < 0.001). The indeterminate QFT results in the inpatient group were independently associated with lymphocytopenia, hypoalbuminemia, and high C-reactive protein levels. Non-positive QFT results in inpatients with TB were associated with lymphocytopenia and hypoalbuminemia, while non-positive QFT results in outpatients with TB were associated with high erythrocyte sedimentation rates and radiographically more severe diseases.
Conclusions
QFT tests in ED-based inpatients with pulmonary infiltrate return indeterminate results relatively frequently. In addition, inpatients and outpatients with pulmonary TB may differ in terms of the risk factors on non-positive QFT results.
doi:10.1186/1471-2334-11-107
PMCID: PMC3107174  PMID: 21513568
17.  The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia 
PLoS Genetics  2010;6(8):e1001051.
Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Author Summary
Worldwide, approximately 15% of lung cancer cases occur among nonsmokers. Genome-wide association studies (GWAS) of lung cancer conducted in populations of European background have identified three regions on chromosomes 5, 6, and 15 that harbor genetic variants that confer risk for lung cancer. Prior studies were conducted primarily in cigarette smokers, raising the possibility that the associations could be related to tobacco use, lung carcinogenesis, or both. A GWAS of lung cancer among never-smokers is an optimal setting to discover effects that are independent of smoking. Since most women in Asia do not smoke, we conducted a GWAS of lung adenocarcinoma among never-smoking females (584 cases, 585 controls) in Taiwan, and observed a region on chromosome 5 significantly associated with risk for lung cancer in never-smoking women. The finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls. To our knowledge, this study is the first reported GWAS of lung cancer in East Asian women, and together with the replication studies represents the largest genetic association study in this population. The findings provide insight into the genetic contribution of common variants to lung carcinogenesis.
doi:10.1371/journal.pgen.1001051
PMCID: PMC2916850  PMID: 20700438
18.  TP53 Mutations in Korean Patients with Non-small Cell Lung Cancer 
Journal of Korean Medical Science  2010;25(5):698-705.
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.
doi:10.3346/jkms.2010.25.5.698
PMCID: PMC2858827  PMID: 20436704
Lung Neoplasms; Mutation; Genes, p53
19.  Venous Thromboembolism in Korean Patients Undergoing Major Orthopedic Surgery: A Prospective Observational Study using Computed Tomographic (CT) Pulmonary Angiography and Indirect CT Venography 
In patients undergoing major orthopedic surgery, data of deep venous thrombosis (DVT) and pulmonary embolism (PE) are lacking as studied by computed tomographic (CT) pulmonary angiography and indirect CT venography (CTPA-CTV). A prospective observational study was performed for 363 Korean patients undergoing major orthopedic surgery to determine the incidence of venous thromboembolism (VTE), especially proximal DVT and PE. The incidence of VTE was 16.3% (n=59). Of them, 8 patients (2.2%) were symptomatic. The rate of VTE was the highest in patients who underwent total knee replacement (40.4%), followed by hip fracture surgery (16.4%), and total hip replacement (8.7%; P<0.001). The incidence of PE was 6.6% (n=24). Of them, 4 patients (1.1%) were symptomatic. Forty-one patients (11.3%) were in the proximal DVT or PE group. Based on multivariate analysis, total knee replacement and age ≥65 yr were significant risk factors for proximal DVT or PE in patients undergoing major orthopedic surgery (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.1; P=0.025; and OR, 2.1; 95% CI, 1.0-4.4; P=0.046, respectively). Taken together, the overall incidence of PE was 6.6% and rate of symptomatic PE rate was 1.1%. Knee joint replacement and age ≥65 yr were significant risk factors for proximal DVT or PE.
doi:10.3346/jkms.2010.25.1.28
PMCID: PMC2800021  PMID: 20052344
Orthopedics; Venous Thromboembolism; Pulmonary Embolism; Computed Tomography
20.  SERPINE2 Polymorphisms and Chronic Obstructive Pulmonary Disease 
Journal of Korean Medical Science  2009;24(6):1119-1125.
A number of genome-wide linkage analyses have identified the 2q33.3-2q37.2 region as most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesized that the SERPINE2 gene, which is one of the genes located at the 2q33.3-2q37.2 region, may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, the association of four SERPINE2 single nucleotide polymorphisms (SNPs; rs16865421A>G, rs7583463A>C, rs729631C>G, and rs6734100C>G) with the risk of COPD was investigated in a case-control study of 311 COPD patients and 386 controls. The SNP rs16865421 was associated with a significantly decreased risk of COPD in a dominant model for the polymorphic allele (adjusted odds ratio [OR]=0.66, 95% confidence interval [CI]=0.45-0.97, P=0.03). In haplotype analysis, the GACC haplotype carrying the polymorphic allele at the rs16865421 was associated with a significantly decreased risk of COPD when compared to the AACC haplotype (adjusted OR=0.58, 95% CI=0.38-0.89, P=0.01), and this effect was evident in younger individuals (adjusted OR=0.30, 95% CI=0.14-0.64, P=0.002). This study suggests that the SERPINE2 gene contributes to the susceptibility to COPD.
doi:10.3346/jkms.2009.24.6.1119
PMCID: PMC2775861  PMID: 19949669
Serpine2; Polymorphism; Pulmonary Disease, Chronic Obstructive
21.  Characteristics of Mechanical Ventilation Employed in Intensive Care Units: A Multicenter Survey of Hospitals 
Journal of Korean Medical Science  2008;23(6):948-953.
A 1D point-prevalence study was performed to describe the characteristics of conventional mechanical ventilation in intensive care units (ICUs). In addition, a survey was conducted to determine the characteristics of ICUs. A prospective, multicenter study was performed in ICUs at 24 university hospitals. The study population consisted of 223 patients who were receiving mechanical ventilation or had been weaned off mechanical ventilation within the past 24 hr. Common indications for the initiation of mechanical ventilation included acute respiratory failure (66%), acute exacerbation of chronic respiratory failure (15%) (including tuberculosis-destroyed lung [5%]), coma (13%), and neuromuscular disorders (6%). Mechanical ventilation was delivered via an endotracheal tube in 68% of the patients, tracheostomy in 28% and facial mask with noninvasive ventilation (NIV) in 4%. NIV was used in 2 centers. In patients who had undergone tracheostomy, the procedure had been performed 16.9±8.1 days after intubation. Intensivists treated 29% of the patients. A need for additional educational programs regarding clinical practice in the ICU was expressed by 62% of the staff and 42% of the nurses. Tuberculosis-destroyed lung is a common indication for mechanical ventilation in acute exacerbation of chronic respiratory failure, and noninvasive ventilation was used in a limited number of ICUs.
doi:10.3346/jkms.2008.23.6.948
PMCID: PMC2610657  PMID: 19119434
Respiration, Artificial; Intensive Care Units; Respiratory Insufficiency; Tuberculosis-Destroyed Lung
22.  Duplication of the Extrahepatic Bile Duct in Association with Choledocholithiasis as Depicted by MDCT 
Korean Journal of Radiology  2008;9(6):550-554.
We report here on an extremely rare case of duplicated extrahepatic bile ducts that was associated with choledocholithiasis, and this malady was visualized by employing the minimum intensity projection images with using multi-detector row CT. The presence of duplicated extrahepatic bile ducts with a proximal communication, and the ducts were joined distally and they subsequently formed a single common bile duct, has not been previously reported.
doi:10.3348/kjr.2008.9.6.550
PMCID: PMC2627237  PMID: 19039272
Bile ducts, abnormalities; Bile ducts, calculi; Computed tomography (CT), minimum intensity projection
23.  Factors Influencing Residual Pleural Opacity in Tuberculous Pleural Effusion 
Journal of Korean Medical Science  2008;23(4):616-620.
Tuberculous pleural effusion (TPE) leads to residual pleural opacity (RPO) in a significant proportion of cases. The aim of this study was to investigate which TPE patients would have RPO following the treatment. This study was performed prospectively for a total of 60 TPE patients, who underwent pleural fluid analysis on the initial visit and chest radiographs and computed tomography (CT) scans before and after the administration of antituberculous medication. At the end of antituberculous medication, the incidence of RPO was 68.3% (41/60) on CT with a range of 2-50 mm. Compared with the non-RPO group, the RPO group had a longer symptom duration and lower pleural fluid glucose level. On initial CT, loculation, extrapleural fat proliferation, increased attenuation of extrapleural fat, and pleura-adjacent atelectasis were more frequent, and parietal pleura was thicker in the RPO group compared with the non-RPO group. By multivariate analysis, extrapleural fat proliferation, loculated effusion, and symptom duration were found to be predictors of RPO in TPE. In conclusion, RPO in TPE may be predicted by the clinico-radiologic parameters related to the chronicity of the effusion, such as symptom duration and extrapleural fat proliferation and loculated effusion on CT.
doi:10.3346/jkms.2008.23.4.616
PMCID: PMC2526418  PMID: 18756047
Computed Tomography; Pleural Effusion; Residual Thickening; Tuberculosis
24.  Relationship between cyclooxygenase 8473T>C polymorphism and the risk of lung cancer: a case-control study 
BMC Cancer  2006;6:70.
Background
Cyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in the COX-2 gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the 8473T>C polymorphism in the 3'-untranslated region of the COX-2 gene and the risk of lung cancer in a Korean population.
Methods
The COX-2 genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender.
Results
The distribution of the COX-2 8473T>C genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined 8473 TC + CC genotype was associated with a significantly decreased risk of adenocarcinoma as compared with the 8473 TT genotype (adjusted OR = 0.64; 95% CI = 0.46–0.90, P = 0.01). On the stratification analysis, the protective effect of the combined 8473 TC + CC genotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91, P = 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93, P = 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87, P = 0.01, respectively).
Conclusion
These findings suggest that the COX-2 8473T>C polymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung.
doi:10.1186/1471-2407-6-70
PMCID: PMC1468421  PMID: 16542464

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