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Telomerase reverse transcriptase (TERT), the catalytic subunit of the enzyme telomerase, is robustly expressed in cancer cells. TERT enables cells to avoid chromosome shortening during repeated replication by maintaining telomere length. However, several lines of evidence indicate that many cancer cells exhibit shorter telomere length than normal tissues, implying an additional function of TERT in tumor formation and progression. Here, we report a telomerase activity-independent function of TERT that induces cancer stemness in glioma cells. Overexpression of TERT712, a telomerase activity-deficient form of TERT, in U87MG cells promoted cell self-renewal in vitro, and induced EGFR expression and formation of gliomas exhibiting cellular heterogeneity in vivo. In patients with glioblastoma multiforme, TERT expression showed a high correlation with EGFR expression, which is closely linked to the stemness gene signature. Induction of differentiation and TERT-knockdown in glioma stem cells led to a marked reduction in EGFR expression, cancer stemness, and anti-cancer drug resistance. Together, our findings indicate that TERT plays a crucial role in tumor progression by promoting cancer stemness through expression of EGFR.

This research aims at determining psychological elements that influence team coordination between a captain and a first officer in a commercial airline cockpit. It also examines how these elements interact between one another in different cultural settings. We propose that mutual inclusiveness of differential status enhances psychological safety and engagement in safety improvement efforts. Survey results based on 254 airline pilots suggest that status (captain, first officer) and mutual inclusiveness (openness between team members) influence psychological safety and mutual inclusiveness moderates the relationship between status and psychological safety. The results also suggest that psychological safety is positively associated with engagement in safety improvement efforts and also mediates the relationship between mutual inclusiveness and improvement efforts. This research provides insights into antecedents of fostering safety improvement efforts in airline crew teams in which cultural differences and professional hierarchy exist.

Analyses of eye tracking and think-aloud protocol data were performed to examine novice-expert differences in perceptual and cognitive aspects of air traffic controllers' situation awareness. In Experiment 1, three groups of field air traffic controllers (experts, intermediates, novices) were asked to perceive situations that were manipulated by situation complexity. In Experiment 2, protocol analysis for previous situation awareness tasks was performed to extract different task models and strategy models as a function of expertise. Then delayed-recall task and interviews about air control plans for the recalled situations were also executed. Results showed that expert controllers concentrate only on several critical features and have their own strategies to reduce mental workloads.

We have established several glioma-relevant oncogene-engineered cancer cells to reevaluate the oncogene-selective cytotoxicity of previously well-characterized anticancer drugs, such as etoposide, doxorubicin, staurosporine, and carmustine. Among several glioma-relevant oncogenes (activated epidermal growth factor receptor, Ras, and Akt, as well as Bcl-2 and p53DD used in the present study), the activated epidermal growth factor receptor, Ras, and Akt exerted oncogenic transformation of Ink4a/Arf−/− murine astrocyte cells. We identified that etoposide, a topoisomerase II inhibitor, caused selective killing of myristylated Akt (Akt-myr)–transduced Ink4a/Arf−/− astrocytes and U87MG cells in a dose- and time-dependent manner. Etoposide-selective cytotoxicity in the Akt-myr–transduced cells was shown to be caused by nonapoptotic cell death and occurred in a p53-independent manner. Etoposide caused severe reactive oxygen species (ROS) accumulation preferentially in the Akt-myr–transduced cells, and elevated ROS rendered these cells highly sensitive to cell death. The etoposide-selective cell death of Akt-myr–transduced cells was attenuated by pepstatin A, a lysosomal protease inhibitor. In the present study, we show that etoposide might possess a novel therapeutic activity for oncogenic Akt-transduced cancer cells to kill preferentially through ROS-mediated damage. [Mol Cancer Ther 2007;6(8):2178–87]

High-grade gliomas are considered the most malignant of brain tumors and have a poor prognosis. In a previous study, we showed that LIM domain only 2 (LMO2) regulates glioma stem cell properties and tumor angiogenesis and gave rise to highly invasive glioma xenografts. Glioma invasion in the surrounding parenchymal tissues is a major hurdle with respect to eliminating glioma by surgery. Invasive glioma cells are considered one of the main culprits for the recurrence of tumors after therapies. In the current study, we focused on determining the molecular mechanism(s) by which LMO2 regulates glioma cell migration and invasion. Forced expression of LMO2 in human U87MG glioma cells led to glioma invasion, as determined by in vivo xenograft assays and enhanced in vitro migration and invasion. LMO2 was associated with increased levels of cytosolic p27(Kip1) protein. LMO2 possibly induced the stabilization and augmented interactions between p27(Kip1) and RhoA. We knocked down the expression of p27(Kip1), which led to a decrease in LMO2-driven glioma cell migration and invasion. Taken together, our findings indicate that LMO2 promotes glioma cell migration and invasion by increasing the levels of cytosolic p27(Kip1).

This research examined how individual differences in personality traits are related with confidence and response bias for situation awareness. Participants completed the big-five personality inventory, the Need for Closure scale inventory, and the unsafe attitude questionnaire followed by a flight situation awareness task designed to assess confidence level and response bias. The data obtained were then analyzed using the framework of Calibration and Signal Detection Theory. The results suggest that extraversion and emotional stability are positively correlated with overconfidence. In addition, extraversion, conscientiousness, and intellect are negatively correlated with response criteria. This suggests that those with lower levels of extraversion, conscientiousness, and intellect are likely to use more conservative response criteria. Our findings have a practical implication that student pilots' personality factors should be considered for effective pilot training.

Most of the aviation research on shared understanding have focused on coordination between cockpit crew. But coordination between pilots and air traffic controllers (ATCs) is critical for flight safety as well. This research determined whether pilots' perception of risk differs from ACTs' when they face the same flight situation. To assess the differences, we had pilots and ATCs evaluate the risk associated with emergency situations. Our risk rating data showed that there were differences in risk perception between pilots and ATCs. Factor analysis further suggested that pilots' risk perception was based on the immediacy of risk whereas ATCs' perception was based on the responsibility for controlling the emergency situation. This research has a practical implication for effective crew resource management (CRM) training.

How individual differences in cognitive ability influence acquisition and transfer of strategic comparison skills was examined as a function of learning difficulty. Using a cognitive test battery, we classified forty-nine participants into three cognitive ability groups. Participants in each group were trained to compare similar (difficult training) or dissimilar (easy training) stimuli and then transferred to compare novel stimuli. Results suggest that overall individual differences in cognitive ability dictate the optimality of strategic skill development, though the effect of training difficulty on transfer performance varies with cognitive ability. Individuals with a midrange of cognitive ability are the most sensitive to the training context. Results are discussed with respect to the characteristics of strategic skills acquired and transferred.

Genomic instability and apoptosis evasion are hallmarks of cancer, but the molecular mechanisms governing these processes remain elusive. Here, we found that survivin, a member of the apoptosis-inhibiting gene family, and aurora B kinase, a chromosomal passenger protein, were co-overexpressed in the various glioblastoma cell lines and tumors. Notably, exogenous introduction of the aurora B in human BJ cells was shown to decrease cell growth and increase the senescence-associated beta-galactosidase activity by activation of p53 tumor suppressor. However, aurora B overexpression failed to inhibit cell proliferation in BJ and U87MG cells transduced with dominant-negative p53 as well as in p53(-/-) mouse astrocytes. Aurora B was shown to increase centrosome amplification in the p53(-/-) astrocytes. Survivin was shown to induce anchorage-independent growth and inhibit anti-proliferation and drug-sensitive apoptosis caused by aurora B. Overexpression of both survivin and aurora B further accelerated the proliferation of BJ cells. Taken together, the present study indicates that survivin should accelerate tumorigenesis by inhibiting the anti-proliferative effect of p53 tumor suppressor that is activated by aurora B in normal and glioblastoma cells containing intact p53.

This research examined the role of working memory (WM) capacity and long-term working memory (LT-WM) in flight situation awareness (SA). We developed spatial and verbal measures of WM capacity and LT-WM skill and then determined the ability of these measures to predict pilot performance on SA tasks. Although both spatial measures of WM capacity and LT-WM skills were important predictors of SA performance, their importance varied as a function of pilot expertise. Spatial WM capacity was most predictive of SA performance for novices, whereas spatial LTWM skill based on configurations of control flight elements (attitude and power) was most predictive for experts. Furthermore, evidence for an interactive role of WM and LT-WM mechanisms was indicated. Actual or potential applications of this research include cognitive analysis of pilot expertise and aviation training.

The study offers insights into pilot ability to anticipate consequences of actions and how this ability changes with experience. Novice and expert pilots completed trials in which 3 screens depicted a control movement (or control movements), a cockpit flight situation, or a change in flight situation. Changes depicted in the 3rd screen of each trial were consistent, inconsistent with the mental model of the effect of the control movement or movements, or inconsistent with the application of the control movement(s) to the current flight situation. Pilots indicated whether the depicted change was inconsistent or consistent with their expectations, and accuracy of consistency judgments was greater for mental-model than for situation-model inconsistent statements. Experts are more accurate than novices, particularly for trials that involve multiple, meaningfully related control movements. Expert ability to organize information into meaningful units appears to facilitate future flight state projections, and projection failures appear to result from situation- rather than mental-model failures. Actual or potential applications of this research include analysis of flight situation awareness and flight performance errors.

Job tasks, such as quality control, require workers to perform visual discriminations, comparing a test stimulus to a standard. In some cases, both stimuli are present and can be compared in parallel. In most cases, however, the standard stimulus is absent and workers must rely on their memory of the standard stimulus in order to make an accurate discrimination. Pratt and Sohn (2001) found that when visual discriminations are made in parallel, training content and individual differences affect strategy development and transfer performance. The present research attempts to compliment and extend Pratt and Sohn's (2001) findings by examining the role of display design and its affects on training effectiveness and strategy development. Participants were given a visual discrimination task identical to Pratt and Sohn's methodology, except stimulus sets were presented serially rather than in parallel. After training with either highly similar or highly dissimilar stimuli, participants transferred to novel stimuli of medium similarity level. Preliminary findings indicate that manipulating display design does not impact training results. Just as Pratt and Sohn discovered, training content does not influence transfer performance for individuals with an analytic cognitive style, but hard training is necessary for individuals with a holistic cognitive style to perform as well as the analytic group. Graphical design and individual differences in cognitive style are discussed.

The present research examines cognitive processes that support flight situation awareness (SA). Of particular interest is pilot access to condition-action rules that reflect their mental models of flight, and their ability to determine when the rules apply in the context of a specific situation. Pilots were asked to reason about events that take place during flight in multiple 3-screen computer-based trials. In each trial, the first screen indicated a control movement, the second screen depicted a meaningful flight situation, and the third screen indicated a flight situation change. Pilots were asked to judge whether the change depicted in the third screen was consistent with what was expected following application of the control movement depicted in the first screen to the flight situation depicted in the second screen. Judgment accuracy suggests superior access to mental models versus situation models, and systematic differences in knowledge organization as a function of piloting expertise.

Described is a program of research that uses rigorous methods to evaluate models of user cognition and action based on the construction-integration architecture of comprehension (Doane and Sohn, 2000; Kintsch, 1988; 1998). The models interrelate user environmental information, background knowledge, and current goals, and then spread activation throughout the interrelated information to simulate UNIX user command productions, aviation pilot eye fixations and control movements during flight, and army personnel intelligence planning. Models of individuals in the complex interactive environments are tested for descriptive as well as predictive validity. Comparisons of model and human empirical data have resulted in a high degree of agreement, validating the ability of the comprehension-based architecture to support models that can predict user performance. Evaluation methods are detailed and the importance of evaluative rigor is discussed.

The present study examined how training difficulty interacts with individual differences in visual processing strategy. Participants discriminated between random polygon stimuli that varied both in both complexity and similarity. Individual processing strategies were categorized into either “holistic” or “analytic” strategy types based on the discrimination latency as a function of polygon complexity. Training difficulty was defined by the similarity of the stimuli being discriminated. Both strategy groups discriminated between similar (“hard” training) or dissimilar stimuli (“easy” training) and then between novel polygons in a transfer stage. Results showed that individual differences in processing strategy interact with training difficulty to influence performance on transfer to novel stimuli. The effect of training on transfer performance was greater for the participants with a holistic strategy than for those with an analytic strategy. The implications for training and display design are discussed.

This research focused on novice-expert differences in memory components of flight situation awareness. In Experiment 1, pilot memory for different forms (spatial or verbal) of cockpit situational information was tested immediately after presentation of the information (immediate recall) or after 30-s delay filled with an intervening task (delayed recall). In Experiment 2, pilot performance on a situation awareness (SA) task was examined and correlated with memory measures obtained in Experiment 1. Results suggest that an expertise effect occurs in delayed recall but not in immediate recall and representation of situational information in memory required to perform a SA task varies as a function of expertise. Theoretical accounts of results are discussed in the context of psychological theories of expertise.

본 연구에서는 직업운전자의 자극추구성향과 직무소진의 관계에서 A형 운전행동 패턴의 매개효과를 검증하고, 이와 같은 매개경로를 일의 의미가 완충시키는 조절효과를 조절된 매개모형으로 검증하였다. 이를 위해 경기도 소재의 운수업체에 재직 중인 운전자 188명을 대상으로 자극추구성향척도, A형 운전행동 패턴 척도, 직무소진 척도, 일의 의미 척도를 통하여 설문을 진행하였고, SPSS 21.0과 SPSS Macro PROCESS를 분석에 활용하였다. 연구결과를 요약하면 다음과 같다. 첫째, 개인의 자극추구성향이 직무소진으로 이어지는 경로에서 A형 운전행동 패턴의 매개효과가 검증되었다. 둘째, 자극추구성향이 A형 운전행동 패턴을 통해 직무소진에 미치는 영향을 미치는 경로에서 일의 의미의 조절된 매개효과를 검증한 결과, 매개 경로가 일의 의미에 의해 조절되는 것으로 나타남을 통해서 조절된 매개효과가 검증되었다. 이와 같은 결과를 바탕으로 본 연구는 운전자의 심리적 건강 및 운전수행에 영향을 줄 수 있는 자극추구성향 성격특성과 A형 운전행동 패턴의 부정적인 측면, 그리고 이러한 부정적인 영향을 완충할 수 있는 일의 의미의 긍정적 효과를 논의하였다.

Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27(KIP1)-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27(KIP1) and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27(KIP1) and MMP3 expression.

Aberrant activation of receptor tyrosine kinases (RTK) is causally linked to the pathobiological traits of glioblastoma and genesis of glioma stem-like cells (GSC), but the underlying mechanism is still unknown. Here, we show that epidermal growth factor receptor (EGFR) signaling regulates the proliferation, angiogenesis, and acquisition of GSC characteristics by inducing inhibitor of differentiation 3 (ID3) and ID3-regulated cytokines [GRO1 and interleukins (IL)-6 and 8] induction. We found that EGFR-mediated ID3 expression was regulated by Smad5, which was directly phosphorylated by AKT. Furthermore, ID3 alone imparted GSC features to primary astrocytes derived from Ink4a/Arf-deficient mouse, and EGFR–ID3–IL-6 signaling axis gave rise to tumor cell heterogeneity. Conversely, EGFR inhibitors suppressed EGFR-AKT-Smad5–driven induction of ID3, which led to a decrease in the tumorsphere forming ability of GSCs and U87MG cells that possess an active mutant EGFR, EGFRvIII, without obvious cytotoxic effects. However, these cells seemed to regain colonogenic ability after removal of the EGFR inhibitors. Together, the results delineate a novel integrative molecular mechanism in which the RTK-ID signaling pathway governs genesis and maintenance of GBM histopathologic features, such as GSCs-based tumor initiation, progression, and angiogenesis. Cancer Res; 71(22); 7125–34. ©2011 AACR.

Glioma stem cells (GSC) possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Thus, they are considered to be major drivers for glioma initiation, progression, and recurrence. However, the precise mechanism governing acquisition of their drug resistance remains to be elucidated. Our previous study has shown that inhibitor of differentiation 4 (ID4) dedifferentiates Ink4a/Arf−/− mouse astrocytes and human glioma cells to glioma stem-like cells (induced GSCs or iGSCs). In this article, we report that ID4-driven iGSCs exhibit chemoresistant behavior to anticancer drugs through activation of ATP-binding cassette (ABC) transporters. We found that ID4 enhanced SOX2 protein expression by suppressing microRNA-9* (miR-9*), which can repress SOX2 by targeting its 3′-untranslated region. Consequently, ID4-mediated SOX2 induction enhanced ABCC3 and ABCC6 expression through direct transcriptional regulation, indicating that ID4 regulates the chemoresistance of iGSCs by promoting SOX2-mediated induction of ABC transporters. Furthermore, we found that short hairpin RNA-mediated knockdown of SOX2 in ID4-driven iGSCs resulted in loss of cancer stemness. Moreover, ectopic expression of SOX2 could dedifferentiate Ink4a/Arf−/− astrocytes and glioma cells to iGSCs, indicating a crucial role of SOX2 in genesis and maintenance of GSCs. Finally, we found that the significance of the ID4-miR-9*-SOX2-ABCC3/ABCC6 regulatory pathway is recapitulated in GSCs derived from patients with glioma. Together, our results reveal a novel regulatory mechanism by which ID4-driven suppression of miR-9* induces SOX2, which imparts stemness potential and chemoresistance to glioma cells and GSCs. Cancer Res; 71(9); 3410–21. ©2011 AACR.

Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) is technically difficult in the patients with large extrahepaic bile duct stones. Small endoscopic sphincterotomy combined with large-balloon dilation (ESLBD) currently seems to be a promising alternative for patients with difficult bile duct stones that cannot be extracted by EST. This study compared the therapeutic benefits and complication rates of ESLBD with those of EST alone. This study investigated 149 patients treated for stones (≥10 mm) or multiple stones in the extrahepatic bile duct. The ESLBD group (n = 72) was compared with the conventional EST group (n = 77). Mechanical lithotripsy was performed when the stone could not be removed using a Dormia basket. The two groups did not differ significantly in terms of mean bile duct diameter, common bile duct angulation, and presence of periampullary diverticulum. The ESLBD group compared with the EST-alone group had similar outcomes in terms of overall successful stone removal but showed significant differences in complete stone removal during the first session (87.5 vs. 74.0%; P = 0.036) and the use of mechanical lithotripsy for large bile duct stones (≥15 mm) (17.9 vs. 45.8%; P = 0.026). For the patients with a periampullary diverticulum, ESLBD and EST showed similar results only for efficacy and complications. The ESLBD technique may be a safe, effective alternative to conventional EST for endoscopic removal of large common bile duct stones, and it can reduce the use of mechanical lithotripsy compared with EST alone.

Question: A 67-year-old man presented for routine health checkup. He did not have any specific gastrointestinal (GI) symptoms. On examination, his vital signs were normal and abdominal examination was unremarkable. Complete blood count showed a white blood cell count of 6300/ L, and a platelet count of 295,000/ L. Hemoglobin concentration was 15.1 g/dL. Hepatic enzymes, lipid profile, blood urea nitrogen, and creatinine levels were normal. Serum glucose was 119 mg/dL, but HbA1c level was normal. The chest radiograph and plain abdomen showed no abnormal findings. Colonoscopy was performed and several small polyps were found in the ascending and transverse colon. And a short pedunculated polypoid mass (15 mm long, 8 mm in diameter) was found in the sigmoid colon (Figure A). This lesion was covered with normal-appearing mucosa and the top was flat and slightly depressed. After polypectomy of polyps, the mass in sigmoid colon was also resected using snare (Figures B, C). What is the endoscopic and pathologic diagnosis? See the GASTROENTEROLOGY web site (www.gastrojournal. org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. YONG SUNG KIM, MD, PhD JI EUN RA, MD YOUNG WOO SOHN, MD, PhD Department of Gastroenterology Wonkwang Digestive Disease Research Institute Wonkwang University Sanbon Hospital Gunpo, South Korea

Here, we show that H-ras(V12) causes the p53-knockout mouse astrocytes (p53-/- astrocytes) to be transformed into brain cancer stem-like cells. H-ras(V12) triggers the p53-/- astrocytes to express a Nestin and a Cd133, which are expressed in normal and cancer neural stem cells. H-ras(V12) also induces the formation of a single cell-derived neurosphere under neural stem cell culture conditions. Furthermore, H-ras(V12)-overexpressing p53-/- astrocytes (p53-/-ast-H-ras(V12)) possess an in vitro self-renewal capacity, and are aberrantly differentiated into Tuj1-positve neurons both in vitro and in vivo. Amongst a variety of Ras-mediated canonical signaling pathways, we demonstrated that the MEK/ERK signaling pathway is responsible for neurosphere formation in p53-deficient astrocytes, whereas the PI3K/AKT signaling pathway is involved in oncogenic transformation in these cells. These findings suggest that the activation of Ras signaling pathways promotes the generation of brain cancer stem-like cells from p53-deficient mouse astrocytes by changing cell fate and transforming cell properties.

The basic helix-loop-helix myogenic regulatory factors play critical roles in skeletal myogenesis. Among the myogenic regulatory factors (MRFs), MRF4 shows a biphasic expression pattern during the formation of myotomes, although its function remains unclear. In this study, we used BEF (spontaneously immortalized bovine embryonic fibroblast that shows myogenic differentiation by overexpression of MyoD) and C2C12 cells to investigate the function of MRF4. Ectopic expressions of MRF4 did not stimulate myogenic differentiation in the BEF and C2C12 cells, but did show a marked increase of cell proliferation, upregulation of cyclin E, and downregulation of p21WAF1. Furthermore, MRF4 was found to induce degradation of the MyoD protein, which acts as a transcriptional activator for p21WAF1, and thus indicates that MRF4 accelerates cell proliferation by suppressing MyoD-dependent p21WAF1 expression. However, forced expression of MyoD in the MRF4-overexpressing cells inhibited cell proliferation and partially induced myogenic differentiation, which suggests that MyoD is a potential negative intercessor of MRF4 in the regulation of the cell cycle. Taken together, these results indicate that MRF4 and MyoD play competitive roles in myogenesis by stimulating cell proliferation and differentiation, respectively.

A biloma is an encapsulated bile collection outside the biliary tree. Most cases of biloma are caused by iatrogenic injury or trauma. Intrahepatic rupture of the biliary tree due to nontraumatic cause is a rare event. A 68- year-old man was admitted because of abdominal pain and fever. He had no past history of abdominal surgery, instrumentation or trauma. Computed tomography (CT) scan and magnetic resonance cholangiopancreatography (MRCP) demonstrated a large subcapsular fluid collection in the right liver associated with choledocholithiasis and cholecystitis. Biloma was confirmed by sono-guided percutaneous needle aspiration and was drained through a pigtail catheter. After the successful treatment by percutaneous drainage and endoscopic sphincterotomy, the patient recovered. Here, we report an uncommon case of spontaneous biloma formation in association with choledocholithiasis with a review of literatures.

In the present research, we examined the relative roles of domain-general and domain-specific individual difference characteristics in complex cognitive task performance. Specifically, we examined the impact both of working memory (WM) capacity and of acquired skills used to encode presented information in an accessible form in long-term working memory (LTWM) on performance in a complex aviation task environment. Measures of WM capacity and LTWM skill served as performance predictors. A criterion measure of task performance was related to the predictor measures. The results indicated that an increase in LTWM skill decreases the role of WM capacity as the determinant of complex task performance, although both measures are important performance predictors. We discuss how the two distinct WM constructs coexist and interact to support complex task performance.

Autoimmune hepatitis (AIH) has been reported in association with Sjögren's syndrome (SS). Drug-induced AIH has been rarely reported. A rare case of the co-development of AIH and SS in a 53-year-old woman after the consumption of herbal medicines is described. After admission, the patient complained of dryness in her mouth, and she was subsequently diagnosed with SS, which had not been detected previously. The patient's bilirubin and aminotransferase levels initially decreased following conservative management; however, they later began to progressively increase. A diagnosis of AIH was made based on the scoring system proposed by the International Autoimmune Hepatitis Group. The patient was administered a combination of prednisolone and azathioprine, and the results of follow-up liver-function tests were found to be within the normal range. This is an unusual case of AIH and SS triggered simultaneously by the administration of herbal medicines.

AIM: To determine the utility of endoscopic ultrasound-guided biliary drainage (EUS-BD) with a fully covered self-expandable metal stent for managing malignant biliary stricture. METHODS: We collected data from 13 patients who presented with malignant biliary obstruction and underwent EUS-BD with a nitinol fully covered self-expandable metal stent when endoscopic retrograde cholangiopancreatography (ERCP) fails. EUS-guided choledochoduodenostomy (EUS-CD) and EUS-guided hepaticogastrostomy (EUS-HG) was performed in 9 patients and 4 patients, respectively. RESULTS: The technical and functional success rate was 92.3% (12/13) and 91.7% (11/12), respectively. Using an intrahepatic approach (EUS-HG, n = 4), there was mild peritonitis (n = 1) and migration of the metal stent to the stomach (n = 1). With an extrahepatic approach (EUS-CD, n = 10), there was pneumoperitoneum (n = 2), migration (n = 2), and mild peritonitis (n = 1). All patients were managed conservatively with antibiotics. During follow-up (range, 1-12 mo), there was re-intervention (4/13 cases, 30.7%) necessitated by stent migration (n = 2) and stent occlusion (n = 2). CONCLUSION: EUS-BD with a nitinol fully covered self-expandable metal stent may be a feasible and effective treatment option in patients with malignant biliary obstruction when ERCP fails.

Su1391 Value of Cytology Combined With Histology by EUS-FNA in the Solid Pancreatic Mass and Intra-Abdominal Lymphadenopathy Tae Hyeon Kim, Young Woo Sohn, Jun Young Lee, Keum Ha Choi, Hyo Jeong Oh Internal Medicine, Wonkwang University Hospital, Iksan, Republic of Korea; Internal Medicine, Wonkwang Unversity Hospital, Sanbon, Republic of Korea; Pathology, Wonkwang University hospital, Iksan, Republic of Korea Background and Aim: Endoscopic ultrasound guided fine-needle aspiration (EUSFNA) is a safe and accurate technique for diagnosing pancreatic tumor. Small core biopsies can be obtained with conventional EUS-FNA. Although most studies have concentrated on the cytology of specimen, few data existed on the histologic assessment. The aim of this study were to determine whether core biopsies by conventional EUS-FNA can increase the accuracy of EUS-guided sampling when combined with cytology when no on-site cytopathologist is present. Method: In the 66 consecutive patients(68 lesions) undergoing EUS-FNA of solid pancreatic masses and intra-abdominal lymphadenopathy between May/ 2009 and July/2010 at a tertiary university hospital without on-site pathologist, adequate tissue coil from the needle were harvested for histology; residual tissue was examed for cytology. The adequacy of sampling, the sensitivities, specificities and overall accuracies of cytology or histology alone and combined cytology-histology were determined. Result: 66 patients ( 38 male and 28 female, mean age 64.9 10.9) with 68 lesions were enrolled. Adequate samples were obtained by EUS-FNA cytology, histology, and combined cytology-histology in 93.8%, 69.2%, 95.4% of patients, respectively. From the pancreas (n 44), adequate samples for histology were obtained by FNA in 78.5%, compared with 52.2% from non-pancreatic cases (n 24), respectively (p 0.01). The significant factors affecting the rate of adequate sample for histology were mass size ( 2cm), malignant lesion, and pancreatic lesion(p 0.05). Overall sensitivity and accuracy of EUS-FNA was 81.9% and 84.6% for cytology alone, 60.0% and 63.1% for histology alone, and 88.2% and 89.2% for combined cytology-histology, respectively (p 0.01, compared to cytology alone). Conclusion: This study shows that combined cytology and histology analysis in diagnosing pancreatic mass and intra-abdominal lymphadenopathy may increase the sensitivity and accuracy of conventional EUS-FNA.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) has recently been found to be a novel component of metabolic syndrome (MS), which is one of the leading causes of chronic liver disease. The serum alanine aminotransferase (ALT) and γ -glutamyltransferase (GGT) levels are suggested to affect liver fat accumulation and insulin resistance. We assessed the associations of serum ALT and GGT concentrations within the reference ranges with MS and NAFLD. Methods: In total, 1,069 subjects enrolled at the health promotion center of Wonkwang University Hospital were divided into 4 groups according to serum ALT and GGT concentrations levels within the reference ranges. We performed biochemical tests, including liver function tests and lipid profiles, and diagnosed fatty liver by ultrasonography. Associations of ALT and GGT concentrationgrading within the reference range with fatty liver and/or MS were investigated. Results: The presence of MS, its components, and the number of metabolic abnormalities (except for high-density lipoprotein-cholesterol (HDL-C) and fasting blood glucose) increased with the ALT level, while the presence of MS, its components, and the number of metabolic abnormalities (except for HDL-C) increased with the GGT level. The odds ratios for fatty liver and MS increased with the ALT level (P