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No single effective method has yet been established for the prophylactic treatment of gastric fundal varices at high risk for bleeding. A prospective, randomized trial was conducted to compare the efficacy and safety of a new technique, balloon-occluded endoscopic injection sclerotherapy (BO-EIS), to balloon-occluded retrograde transvenous obliteration (B-RTO) for treatment of high-risk gastric fundal varices.Twenty consecutive patients with gastric variceal diameters of over 5 mm by color Doppler EUS were randomized to undergo either BO-EIS or B-RTO. All patients underwent color Doppler EUS 2 weeks after treatment and EGD every 3 months for assessment of sclerosing effect.The gastric varices in all patients except one in the B-RTO group were eradicated with either treatment. The volume of sclerosant used was significantly smaller in patients who underwent BO-EIS (p0.05). The endoscopic grade of esophageal varices in 4 of 9 patients worsened after treatment with B-RTO (p0.05). The method of randomization used resulted in an uneven distribution of women, although the difference between the groups was not statistically significant. When only men were compared, the results of the study were unchanged.BO-EIS is a safe and effective for treatment of high-risk gastric fundal varices. In contrast to B-RTO, it can be used even in patients without a gastrorenal shunt.

Dynamic damping analysis study of hybrid composite laminated plate structures and their tailoring aspects to enhance dynamic behavior have been discussed in this paper. The present analytical formulation is based on an integrated approach in which the lamina level micromechanics based theory is combined with a higher-order transverse shear deformable plate theory to predict the equivalent material specific damping capacity (SDC) of a general hybrid composite laminated plate structure. The micromechanical equations based on a self-consistent stress method are used for the calculation of elastic stiffness and SDC at the lamina level. As a typical example, the solution procedures of a steady state dynamic characteristics including the modal SDC of a rectangular laminated plate simply-supported on all the four edges have also been discussed. Specifically, our aim is to evaluate the effects of fiber orientation and the volume fraction of the hybridizing fiber on the dynamic behavior such as, flexural vibration frequencies and the modal SDC of the laminated plate. In order to get a basic understanding about the various tailoring aspects, a parametric optimization was done to get the appropriate fiber volume fractions of hybrid composite to achieve a balanced dynamic performance involving both resonance frequency and modal SDC. Numerical results are furnished for a typical Carbon/E-Glass fiber hybrid composite laminated plate to understand the above mentioned effects. It has been observed that the fiber orientation has a strong influence in controlling the SDC of laminated plate similar to those of the natural frequencies of the plate. The modal SDC of the first three modes indicates that the trend of the SDC variation with respect to laminate fiber angle is in a reversed manner as those of the natural frequencies.

Background and Aims: Autophagy is a normal physiological mechanism for the degradation of cellular proteins and organelles. Excessive autophagy induced by cellular stress leads to cell death. However, the exact role of autophagy in cancer is not completely clear. Beclin1 plays a central role in the regulation of autophagy. The major goal of our study was to evaluate the role of Beclin-1 and autophagy and the effect of bile acids in the esophageal carcinogenesis. Barrett's esophagus (BE) is a premalignant lesion of distal esophagus associated with an increased risk for the development of esophageal adenocarcinoma (EAC). Methods: Beclin-1 expression was evaluated using immunohistochemistry, immunoblotting, or RTPCR in (1) biopsies obtained from 62 patients with BE or EAC, (2) tissues from a rat model of BE and EAC, and (3) esophageal cell lines. Since reflux of bile acids is important in esophageal carcinogenesis, the effect of acute and chronic exposure to deoxycholic acid (DCA) on autophagy and Beclin-1 expression was evaluated. Autophagy was assessed by electron microscopy or by transfection with GFP-LC3 plasmid and calculating the percentage of GFP-LC3 positive cells with punctuate pattern. Results: Our studies using human biopsies and rat tissues showed that Beclin-1 expression was high in squamous epithelium, while its expression was low in BE and EAC. A similar pattern was observed in esophageal cell lines. HET-1A cells (derived from normal squamous epithelium) showed high levels of Beclin-1, but lower levels of Beclin-1 were found in BE cells (CP-A, CP-C) and EAC cells (OE33 cells). Acute exposure to DCA led to increased Beclin-1 expression and increased autophagy in CP-A cells. In contrast, chronic exposure to DCA did not result in any alteration of Beclin-1 or autophagy. To demonstrate that Beclin-1 plays central role in autophagy we used siRNA to decrease Beclin-1 expression and then autophagy was evaluated after treatment with DCA. No increase in autophagy was detected compared to untreated control CP-A cells. Conclusions: In summary, our data suggests that autophagy is initially activated in response to bile acids, but chronic exposure to bile acids leads to decreased Beclin-1 expression and autophagy resistance. We propose that autophagy resistance in combination with apoptosis resistance induced by chronic exposure to bile acids contributes to EAC development.

802 Final Result of a Prospective Non-Randomized Study for Accuracy of Detection and Diagnosis of Esophageal Squamous Cell Carcinoma by Tandem Non-Magnifying Endoscopy With Narrow-Band Imaging and Iodine Staining Yasuaki Nagami*, Hirohisa Machida, Kazunari Tominaga, Masami Nakatani, Natsuhiko Kameda, Satoshi Sugimori, Hirotoshi Okazaki, Tetsuya Tanigawa, Naoshi Kubo, Masatsugu Shiba, Kenji Watanabe, Toshio Watanabe, Yasuhiro Fujiwara, Masaichi Ohira, Tetsuo Arakawa Gastroenterology, Osaka City University Graduate School of Medicine, Osaka City, Japan; Gastroenterology, Ohno Memorial Hospital, Osaka City, Japan; Gastroenterology, Minamiosaka Hospital, Osaka City, Japan; Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka City, Japan Background/Aim: Chromoendoscopy with iodine staining facilitates the detection of esophageal cancer but causes severe chest discomfort. Narrow-band imaging (NBI) also facilitates the detection of esophageal cancer without causing discomfort. However, only few studies have reported the use of non-magnifying endoscopy with NBI for routine screening examination. This prospective nonrandomized study aimed to investigate the efficacy of non-magnifying endoscopy with NBI in detecting esophageal squamous cell carcinoma (SCC) compared to that of chromoendoscopy using iodine. Methods: Between May 2008 and January 2011, 202 patients (M/F 180/22; mean age, 67 years) who had not undergone chemotherapy or radiotherapy were included in this study. Among these patients, 120 had a history of head and neck carcinoma, 78 had previously undergone endoscopic resection (ER) for esophageal cancer, and 4 had a history of head and neck carcinoma and had undergone ER. Endoscopic examination was performed by the same endoscopist using the following modalities: the presence of a well-demarcated brownish area (BA) in NBI or an unstained area with or without pink coloration (PC) after iodine staining. The final diagnoses for all the lesions were determined by pathological evaluations. The sensitivity and specificity of esophageal-cancer diagnosed by NBI was the main outcome and was compared to that by iodine staining as the secondary outcome. Results: Histological examination of 113 lesions for suspected SCC or high-grade intraepithelial neoplasia (HGIN) revealed 31 (27.7%) lesions as SCC or HGIN. NBI detected 49 BAs, including 28 lesions diagnosed as SCC or HGIN on histological examination, thus indicating that the sensitivity and specificity for NBI were 90.3% and 74.4%, respectively. Iodine staining revealed 111 unstained areas, including the 31 lesions; the sensitivity and specificity were 100% and 2.4%, respectively. Further, we observed 38 unstained areas with PC, including 30 lesions; the sensitivity and specificity were 96.8% and 90.2%, respectively. Although the specificity of NBI was superior to that of iodine staining (P 0.01) and inferior to that of PC (P 0.01), there was no significant difference in the sensitivity of NBI and iodine staining (P 0.08). Conclusion: These findings suggest that initial use of non-magnifying endoscopy with NBI for detection of BA lesions and subsequent iodine staining for these lesions would be a promising screening strategy for patients with high risks for esophageal cancers.

of metastasis of GI tract. Position emission tomography (PET)-CT scan is the most sensitive and widely used tool to diagnosed visceral and non-visceral metastasis of melanoma. The aim of the study was to compare agreement between capsule endoscopy (CE) and PET-CT scan in detecting small intestinal metastasis in patients with metastatic melanoma. Patients and Methods: We performed a retrospective analysis of 426 consecutive patients who underwent CE at MD Anderson Cancer Center from July 2005 till September 2011. We identified patients with metastatic melanoma who underwent CE for various indications and compared CE results with results of PET-CT scan done within 1 month duration. We also collected information regarding demographics, sites of metastasis, basic laboratory tests, treatment and date of last known follow up or death. We used SPSS version 19.0.0 (IBM Corporation) for statistical analysis. Agreement between CE and PET-CT scan was detected by Kappa statistics. Kaplan-Meier method was used to generate overall survival curve. Results: We identified 23 patients, who underwent CE for evaluation of small intestinal metastatic melanoma and also had PET-CT scan available for comparison. There were 19 males and 4 females with median age of 56.61 (range: 24 to 83). The indications for CE were anemia (6 cases), melena (6 cases), hematochezia (2 cases), abnormal imaging (6 cases), and clinical suspicion (3 cases). Both CE and PET-CT scan were positive in 11 cases and negative in 12 cases. In 4 cases, where PET-CT scans suggested possible small intestinal metastasis, but subsequent CEs were negative for metastasis. Similarly in 4 cases, the PET-CT scan was negative but CE showed metastatic deposits in the small intestine (Table 1). The agreement between CE and PET-CT scan was found to be only fair, Kappa 0.303 (p 0.146); 95% CI ( 0.08 to 0.69). Out of 8 cases, where CE and PET-CT scan were negative for small intestinal metastasis, one patient subsequently underwent diagnostic and therapeutic laparoscopy and was found to have small intestinal metastatic melanoma. Patients with melanoma and recent history of gastrointestinal bleeding including melena or hematochezia had poor survival compared to patients with melanoma and no history of recent GI bleeding (p 0.04) (Figure 1). Conclusion: The agreement between CE and PET-CT scan is fair in evaluation of small bowel metastatic melanoma. Neither CE nor PET-CT scan diagnoses the small bowel metastasis of melanoma with 100% sensitivity. CE and PET-CT scan should be used as complimentary to each other for evaluation of small bowel metastasis of melanoma.

onwards when compared between groups 44 weeks vs. 18 weeks in all treatment conditions. Proliferation rate was significantly (P

Usefulness of Narrow-Band Imaging in Delineating Early Gastric Cancer Sayoko Nakayama, Hirohisa Machida, Kazunari Tominaga, Masatsugu Shiba, Yasuaki Nagami, Satoshi Sugimori, Masami Nakatani, Natsuhiko Kameda, Hirotoshi Okazaki, Hirokazu Yamagami, Tetsuya Tanigawa, Kenji Watanabe, Toshio Watanabe, Yasuhiro Fujiwara, Tetsuo Arakawa Osaka City University Graduate School of Medicine, Osaka, Japan; Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan [Background & Aims]: Endoscopic submucosal dissection (ESD) has been widely accepted as an endoscopic therapy for early gastric cancer (EGC), to obtain a precise pathological diagnosis and promising curability for EGC. Appropriately margining resection at will is one of distinctive features of ESD, therefore, the precise estimation for the lateral extent of the lesion has an important role in successful ESD. The aim of this study is to investigate the usefulness in delineating the lateral extent of EGC using narrow-band imaging (NBI) endoscopy with magnification. [Methods]: February 2004 to October 2010, a total of 503 patients who underwent ESD for EGC achieving en bloc resection were enrolled in this study from. Patients were assigned to two groups, according to whether or not they underwent NBI endoscopy with magnification before ESD; Group A: 37 lesions evaluated with chromoendoscopy, as a historical control and group B: 465 lesions evaluated with NBI endoscopy. As outcome measures, complete resection rate (defined as en bloc resection and cancer free margin), location, size, macroscopic type, histology and presence of ulcer scar (UL) were compared between groups. In estimating the lateral extent, the margin was determined according to surface structure of mucosa in chromoendoscopy with indigo-carmine dye spraying and the presence of irregular microvascular pattern and demarcation line which were specific for EGC in NBI endoscopy. [Results]: Complete resection rate in group B was superior to that in group A (98.3% (8/ 465) vs. 91.9% (34/37), p 0.01). The incidence of incomplete resection was as followed; 1) Location; upper/ middle/ low: 1.5% (2/132)/ 3.5% (5/144)/ 0.5% (1/ 189), 2) Size; less than 20mm/ over 20mm: 1.3% (4/305)/ 2.5% (4/160), 3) Macroscopic type; elevated/ flat/ depressed: 0% (0/244)/ 6.7% (1/15)/ 3.4% (7/ 206), 4) Histology; differentiated/ undifferentiated: 1.3% (6/446)/ 5.3% (2/38), 5) Presence of an ulcer scar; 6.2%(5/81)/ 0.8% (3/384). As a result of univariate analysis in group B, complete resection rate was significantly inferior in the point of macroscopic type (p 0.01), presence of UL (p 0.01) and histology (p 0.027), in comparison with cancer positive and negative in margin. And it was not significant in location and size. In multivariate analysis, it was significant in the point of histology (p 0.025) and presence of UL (p 0.025). [Conclusions]: NBI endoscopy with magnification might be usefulness in an appropriate delineating the lateral extent of EGC. Features of histology or ulcer scar may affect the accurate endoscopic marginal estimation for EGC even though using NBI endoscopy.

Background: Patients with functional dyspepsia (FD) tend to be more depressed and anxious than healthy controls but what comes first is not clear. We hypothesized that psychological morbidity can be secondary to abnormal gastrointestinal afferent signaling. We therefore evaluated depression-like and anxiety-like behaviors and the sensitivity to stress in a previously described rat model of FD. Methods: 10 days old male Sprague-Dawley rats received 0.2 ml of 0.1% iodoacetamide (IA) in 2% sucrose daily by oral gavages for 6 days. Control group received 2% sucrose. At 8-10 weeks of age, sucrose preference test (SPT) and forcedswim test (FST) were used for testing depression-like behavior and elevated plus maze (EPM) and open field test (OFT) were used to test anxiety-like behaviors. Subsequently plasma ACTH, corticosterone and oxytocin levels in response to a minor stressor (subcutaneous saline injection) were measured. RNA was extracted from various brain regions. Results: Rats with neonatal gastric irritation (NGI) showed several abnormalities on the FST as compared with control (Immobility: 32.4± 3.95 vs. 12.95±2.80, climbing: 7.05± 1.18 vs. 18.65 ±1.9 and swimming: 20.6± 3.02 vs. 28.35± 2.1, P 75% of total intake) was decreased in NGI rats (45% versus 80%; p

Background& Aims: Visceral perception of functional dyspepsia (FD) is based on the braingut interaction via various neurotransmission pathways. Peripheral or central serotonergic abnormalities are associated with the pathophysiology of functional gastrointestinal disorders or psychiatric depression and anxiety. To examine the roles of the cerebral serotonin (5HT) neurotransmission systems in visceral perception of FD patients, we examined both 5HT transporter (5-HTT) binding potential in the brain and the correlation between differences between patients and controls in 5-HTT binding potential and abdominal symptoms. Methods: Patients with FD diagnosed according to the Rome III criteria (N=9, female: 6, age range 25-61 yrs) were recruited for this study. There were 9 healthy controls (female: 3, age range 36-76 yrs). To measure 5-HTT binding potential with region-of-interest data in areas of the thalamus, putamen, caudate, amygdala, midbrain, and cerebellum (as a reference region), positron emission tomography (PET) with [11C]N,N-dimethyl-2-(2-amino4-cyanophenylthio) benzylamine ([11C]DASB), which binds specifically to 5-HTT, was performed. We used the Multi-linear Reference Tissue Mode method within the standard software package of PMOD Technologies for analysis of [11C]DASB with reference to the co-registered MRI images. Clinical symptoms were evaluated on the Gastrointestinal Symptoms Rating Scale (GSRS) including subscales for abdominal pain and indigestion. Depression and anxiety were evaluated on the Self-Rating Depression Scale and the State-Trait Anxiety Inventory. Results: All scores for abdominal pain, indigestion, depression, and anxiety were higher for FD patients than for controls (p

G A A b st ra ct s cell migration was reduced in TSC2(-/-) rat embryonic fibroblast (REF) cells. In addition, an increase of actin stress fiber formation was observed in TSC2(-/-) REF cells upon stimulation with IGF-1. Furthermore, we showed that the activation of Rac-GTPase was largely impaired in both TSC2(-/-) REF and TSC2 knockdown cancer cells, suggesting that maintaining TSC2 expression is required for Rac activation and cell migration. Our results are consistent with the fact that patients with TSC2 mutations only develop benign and nonmetastatic tumors. Collectively, we identified a novel role of TSC2 in controlling cell motility and cytoskeleton rearrangement by regulating Rac activation.