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Su1178 Matrix-Stiffness Enhances Esophageal Fibroblast Activation, Proliferation and Contractility in Pediatric and Adult Fibroblasts
of the SIBO and no additional reoccurrence of the diarrhea. This case highlights the safety of SBI in a pediatric patient with an acute diarrhea due to SIBO and/or antibiotic therapy. SBI may prove to be useful in some acute setting where limited therapeutic options are available. Given that SBI has been designated as a medical food with GRAS (General Recognized As Safe) status for use in the general population, it may serve as an option for children in the nutritional management of chronic loose and frequent stools.
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Background: The new developed endoscopy, GIF-HQ290 & GIF-290N (Olympus Medical System, Tokyo, Japan), can reveal micro surface pattern of gastric mucosa by super close observation. These methods aren't necessary for complicated procedure of magnification. In this study, using the GIF-HQ290 & 290N, we evaluated whether endoscopic diagnosis (discrimination between benign and malignant) of gastric depressive lesions. Subjects and Methods: The subjects were 264 patients who underwent screening of the gastrointestinal tract using GIF-HQ290 & 290N. Their average age was 64.5±9.2 years. The male-female ratio was 2.5:1. All cases were examined using conventional WLI, dye-staining (indigocarmine) and super close observation endoscopy (about 3mm) with NBI (NBI-CE). When a <20 mm depressed lesion was detected in the stomach, it was examined using the three observation technique. We observed the micro surface pattern of the lesion using NBI-CE. Concerning mucosal micro surface pattern, we looked for a clear demarcation line between the lesion and the surrounding mucosa, and loss, irregularity or no uniformity of the lesion. Biopsies were taken from all lesions for histological examination. Result: A total of 61 depressive lesions were examined. The histological diagnosis was cancer for 11 lesions, and non-cancer for 50 lesions. WLI and dye-staining examination yielded sensitivity of 54.5% (6/11), 63.6% (7/11) and specificity of 62.0% (31/50), 70.0% (35/50) respectively. On the other hand, NBI-CE yielded a sensitivity of 81.8% (9/11) and specificity of 88.5% (45/50), significantly higher. Figure show picture of WLI (left), dye-staining (middle) and NBI-CE (right) in early gastric cancer of posterior wall of antrum. Conclusion: NBI-CE using GIF-HQ290&290N enables mucosal diagnosis even without complicated procedure of magnification, and was considered to be an effective technique for improving endoscopic diagnosis.
Su1178 Matrix-Stiffness Enhances Esophageal Fibroblast Activation, Proliferation and Contractility in Pediatric and Adult Fibroblasts Amanda Muir, Kara K. Dods, Steven J. Henry, Alain J. Benitez, Maureen DeMarshall, Gary W. Falk, Rebecca Wells, Daniel A. Hammer, Hiroshi Nakagawa, Mei-Lun Wang Background: Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease that affects patients of all ages. Subepithelial fibrosis is the most significant complication of EoE and leads to dysphagia, food impaction and stricture formation. In EoE, subepithelial fibroblast activation results in increased extra-cellular matrix deposition and stiffness. It is well established that fibroblasts transdifferentiate into activated myofibroblasts when exposed to profibrotic cytokines such as TGFβ. Fibroblasts have also been shown to activate on stiff substrates in the absence of cytokines in other models of fibrosis. In this study, we determine the relationship between esophageal fibroblasts and matrix stiffness using primary esophageal fibroblast (PEF) cell lines from pediatric and adult patients. Methods: Following informed consent, PEFs were isolated from esophageal biopsies from pediatric and adult EoE and control patients ranging in age from 6-52 years. PEFs were seeded on polyacrylamide gels ranging in stiffness from 3 kPa to 12 kPa. Cells were analyzed for proliferation, morphology, and activation status. Microfabricated-Post-Array-Detectors (mPADs) were utilized to quantify single-cell traction forces. Stiffness of these microscopic vertical post arrays is varied by changing the length of the posts while preserving diameter. The soft posts had a spring constant of 7 nN/um and the stiff posts were 33 nN/um. PEFs were seeded on fibronectin printed posts conjugated with AlexaFluor488 to visualize post-deflections in the fluorescence channel. After 18 hours of incubation at 37°C, cells were imaged. Forces were computed by measuring the displacement of the fibroblast-engaged posts relative to their undeflected resting positions and multiplying by the applicable spring constant. Results: Fibroblasts seeded on softer gels had quiescent morphology, decreased cell proliferation and decreased activation as measured by α-smooth muscle actin expression by RT-PCR and immunofluorescence. Fibroblasts seeded on stiff gels had increased spindle morphology, increased proliferation and increased α-SMA expression. Fibroblasts from all phenotypes (EoE and non-EoE adults and children) exhibited consistent findings of proliferation and morphology when placed on matrices of similar stiffness. We found that fibroblasts seeded on softer posts generated on average 4.8 nN/post of force compared to those on stiff posts which generated 31.6 nN/post (p=0.0001). Conclusion: Esophageal fibroblasts are highly responsive to the stiffness of their environment. Fibroblasts transdifferentiate in a stiff environment despite the absence of cytokines or a proinlammatory mileu. Furthermore, fibroblasts respond similarly to environmental stiffness regardless of age or disease status.
Su1181 Does Magnetic Resonance Enterography Influence Management Strategies in Complex Crohn's Disease? Usman I. Aujla, Majid Khan, Adam P. Staten, Sameer Zar INTRODUCTION: The management of Crohn's disease (CD) is largely dependent on knowledge of disease extent and severity of mucosal inflammation. Computed tomography (CT) has an established role in assessment of disease activity and related complications, which could further optimize management strategies. Magnetic resonance enterography (MRE) may be preferred to conventional computed tomography (CT) in evaluating this complex and challenging condition due to absence of hazardous effects of ionizing radiation and its appropriateness for repeated evaluation. AIMS & METHODS: The aim of this study was to assess the role of MRE in evaluating Crohn's disease (CD) and its subsequent management strategies. The integrated hospital electronic database system reviewed retrospectively over a period of two years (Jan 2012- Dec 2013) and analysed for the following: clinical details, radiology, biochemistry, endoscopy and histology. RESULTS: MRE was performed in 69 patients (40 females and 29 males) with mean age of 35yeras (range 1679). Mean duration of illness was 6.32 years (range 0.5-37y). 7 (10%) patients were active smokers. Main indications for performing MRE were symptoms consistent with clinically active disease including abdominal pain, diarrhoea and weight loss and to exclude disease related complications. MRE showed radiological signs of active disease in 46 (66%) patients. MRE confirmed suspected Crohn's disease in eight out of twenty patients (40%) previously being treated as irritable bowel syndrome (IBS). In 28 (40%) patients MRE detected 37 complications (23 strictures, 11 fistulas and 3 abscesses) and was reported normal in 17/ 69 (24.6%) of cases. MRE redefined CD extent in 9 (13%) patients (6 colonic to ileo-colonic and 3 ileal to ileo-jejunal). MRE changed clinical management strategies in 38/69 (55%) patients. 10 (14.5%) were commenced on biologics (8 adalimumab & 2 infliximab); 8 (11.6%) changed to immunomodulators (6 azathioprine & one 6-mercaptopurine & methotrexate each); 3 (4.34%) patients commenced on combination therapy with infliximab and azathioprine and one prescribed budesonide. 15/69 (21.7%) patients had surgery; 3 right hemicolectomies; 4 small bowel resections; 3 strictureplasties; 3 fistula repairs; one colectomy and abscess drainage each and one endoscopic dilatation for small bowel stricture. CONCLUSION: Magnetic resonance enterography is highly useful in managing complex Crohn's disease. It is non-invasive and has no radiation related implications. In our experience it helped to detect disease related complications, redefined disease extent and activity. Particularly it changed clinical management strategies in more than 50% of patients. We recommend utilizing this diagnostic entity to achieve optimum treatment goals in selected cases.
Su1179 Differential Diagnosis of Polypoid Lesions of the Gallbladder Using ContrastEnhanced Ultrasonography With High Mechanical Index Contrast Mode Haruo Miwa, Kazushi Numata, Tomohiro Ishii, Takashi Kaneko, Wataru Shibata, Kazuya Sugimori, Katsuaki Tanaka, Shin Maeda Background and aim: Transabdominal ultrasonography is initially used to detect the polypoid lesions of the gallbladder (PLG); however, it is often difficult to characterize these lesions qualitatively. Contrast-enhanced ultrasonography (CEUS) with high mechanical index (HMI) contrast mode provides us vessel images in detail and we have reported that it was useful for the differential diagnosis of both hepatic and pancreatic lesions. In the present study, we aimed to evaluate the usefulness of CEUS with HMI contrast mode to differentiate PLG. Materials and methods: Between March 2007 and November 2014, 41 patients with PLG underwent CEUS with HMI contrast mode. They included 17 cases with gallbladder cancers, 19 cases with benign polyps, and 5 cases with gallbladder sludge. All cases with gallbladder cancer, 11 cases with benign polyp, and 2 cases with gallbladder sludge were confirmed by pathological results. The other 11 cases were diagnosed by radiological imaging followed up at least for one year. CEUS were performed, using the LOGIQ 7 ulatrasound imaging system (GE Healthcare, Milwaukee, WI) with perflubutane-based contrast agent, Sonazoid (Daiichi Sankyo, Tokyo, Japan). The coded harmonic angio mode (mechanical index = 0.60.9) was chosen for visualizing tumor vessels in detail. Vessel images of PLG were stored until 180 seconds from injection of Sonazoid and retrospectively reviewed by blinded readers. Institutional review board approved this study and informed consent was obtained from all patients. Results: The patients consisted of 24 male and 17 female, ranging in age from 31 to 80 years (mean, 65 years). The size of the lesions ranged from 10 mm to 47mm (mean, 19.5mm). All 5 cases of gallbladder sludges showed no vessel and the other 36 lesions had some type of vessels. The vessel form was categorized into 3 types, dotted vessel, branched vessel, and tortuous vessel. Gallbladder cancers included 14 cases (82%) with tortuous vessels and 3 cases (18%) with branched vessels. Benign polyps included 2 cases (11%) with tortuous vessels, 10 cases (51%) with branched vessels, and 7 cases (37%) with dotted vessels. Dilated vessels were detected in twelve cases (71%) of gallbladder cancer, but they were shown in only 1 case (5%) of benign polyp (p < 0.001). Pedunculated lesions were detected in 16 cases (84%) of benign polyps and 2 cases (12%) of gallbladder cancers (p < 0.001), those were clarified with a vessel flowing into the stalk of PLG. PLG with tortuous vessels or dilated vessels on CEUS with HMI contrast mode were diagnosed as gallbladder carcinomas. The sensitivity, specificity, and accuracy of this diagnosis were 89% (15/17), 92% (22/24), and 90% (37/41), respectively. Conclusion: Vessel images described by CEUS with HMI contrast mode are useful for differential diagnosis of PLG.
Su1182 EUS Guided Biliary Drainage Versus Percutaneous Transhepatic Biliary Drainage: Predictors of Successful Outcome in Patients Who Fail ERCP Reem Z. Sharaiha, Amit P. Desai, Ersilia M. DeFilippis, Sanjay Salgado, Jennifer E. Millman, Andrea M. Benvenuto, Monica Gaidhane, Amy Tyberg, Michel Kahaleh Background: Patients with biliary obstruction and concurrent co-morbidities, failed ampullary access, or altered anatomy have been conventionally offered percutaneous transhepatic biliary drainage (PTBD). While PTBD is effective, it carries risks such as catheter-related complications and chronic pain with poor quality of life. It is also contraindicated in patients with ascites and coagulopathy. There is limited data regarding the emerging role of endoscopic
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AGA Abstracts
AGA Abstracts
Evaluation of Gastric Cancer Diagnosis Using Super Close Observation Endoscopy With Narrow-Band Imaging Takashi Kawai, Kyosuke Yanagisawa, Masakatsu Fukuzawa, Fuminori Moriyasu
Su1180
Background: The new developed endoscopy, GIF-HQ290 & GIF-290N (Olympus Medical System, Tokyo, Japan), can reveal micro surface pattern of gastric mucosa by super close observation. These methods aren't necessary for complicated procedure of magnification. In this study, using the GIF-HQ290 & 290N, we evaluated whether endoscopic diagnosis (discrimination between benign and malignant) of gastric depressive lesions. Subjects and Methods: The subjects were 264 patients who underwent screening of the gastrointestinal tract using GIF-HQ290 & 290N. Their average age was 64.5±9.2 years. The male-female ratio was 2.5:1. All cases were examined using conventional WLI, dye-staining (indigocarmine) and super close observation endoscopy (about 3mm) with NBI (NBI-CE). When a <20 mm depressed lesion was detected in the stomach, it was examined using the three observation technique. We observed the micro surface pattern of the lesion using NBI-CE. Concerning mucosal micro surface pattern, we looked for a clear demarcation line between the lesion and the surrounding mucosa, and loss, irregularity or no uniformity of the lesion. Biopsies were taken from all lesions for histological examination. Result: A total of 61 depressive lesions were examined. The histological diagnosis was cancer for 11 lesions, and non-cancer for 50 lesions. WLI and dye-staining examination yielded sensitivity of 54.5% (6/11), 63.6% (7/11) and specificity of 62.0% (31/50), 70.0% (35/50) respectively. On the other hand, NBI-CE yielded a sensitivity of 81.8% (9/11) and specificity of 88.5% (45/50), significantly higher. Figure show picture of WLI (left), dye-staining (middle) and NBI-CE (right) in early gastric cancer of posterior wall of antrum. Conclusion: NBI-CE using GIF-HQ290&290N enables mucosal diagnosis even without complicated procedure of magnification, and was considered to be an effective technique for improving endoscopic diagnosis.
Su1178 Matrix-Stiffness Enhances Esophageal Fibroblast Activation, Proliferation and Contractility in Pediatric and Adult Fibroblasts Amanda Muir, Kara K. Dods, Steven J. Henry, Alain J. Benitez, Maureen DeMarshall, Gary W. Falk, Rebecca Wells, Daniel A. Hammer, Hiroshi Nakagawa, Mei-Lun Wang Background: Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease that affects patients of all ages. Subepithelial fibrosis is the most significant complication of EoE and leads to dysphagia, food impaction and stricture formation. In EoE, subepithelial fibroblast activation results in increased extra-cellular matrix deposition and stiffness. It is well established that fibroblasts transdifferentiate into activated myofibroblasts when exposed to profibrotic cytokines such as TGFβ. Fibroblasts have also been shown to activate on stiff substrates in the absence of cytokines in other models of fibrosis. In this study, we determine the relationship between esophageal fibroblasts and matrix stiffness using primary esophageal fibroblast (PEF) cell lines from pediatric and adult patients. Methods: Following informed consent, PEFs were isolated from esophageal biopsies from pediatric and adult EoE and control patients ranging in age from 6-52 years. PEFs were seeded on polyacrylamide gels ranging in stiffness from 3 kPa to 12 kPa. Cells were analyzed for proliferation, morphology, and activation status. Microfabricated-Post-Array-Detectors (mPADs) were utilized to quantify single-cell traction forces. Stiffness of these microscopic vertical post arrays is varied by changing the length of the posts while preserving diameter. The soft posts had a spring constant of 7 nN/um and the stiff posts were 33 nN/um. PEFs were seeded on fibronectin printed posts conjugated with AlexaFluor488 to visualize post-deflections in the fluorescence channel. After 18 hours of incubation at 37°C, cells were imaged. Forces were computed by measuring the displacement of the fibroblast-engaged posts relative to their undeflected resting positions and multiplying by the applicable spring constant. Results: Fibroblasts seeded on softer gels had quiescent morphology, decreased cell proliferation and decreased activation as measured by α-smooth muscle actin expression by RT-PCR and immunofluorescence. Fibroblasts seeded on stiff gels had increased spindle morphology, increased proliferation and increased α-SMA expression. Fibroblasts from all phenotypes (EoE and non-EoE adults and children) exhibited consistent findings of proliferation and morphology when placed on matrices of similar stiffness. We found that fibroblasts seeded on softer posts generated on average 4.8 nN/post of force compared to those on stiff posts which generated 31.6 nN/post (p=0.0001). Conclusion: Esophageal fibroblasts are highly responsive to the stiffness of their environment. Fibroblasts transdifferentiate in a stiff environment despite the absence of cytokines or a proinlammatory mileu. Furthermore, fibroblasts respond similarly to environmental stiffness regardless of age or disease status.
Su1181 Does Magnetic Resonance Enterography Influence Management Strategies in Complex Crohn's Disease? Usman I. Aujla, Majid Khan, Adam P. Staten, Sameer Zar INTRODUCTION: The management of Crohn's disease (CD) is largely dependent on knowledge of disease extent and severity of mucosal inflammation. Computed tomography (CT) has an established role in assessment of disease activity and related complications, which could further optimize management strategies. Magnetic resonance enterography (MRE) may be preferred to conventional computed tomography (CT) in evaluating this complex and challenging condition due to absence of hazardous effects of ionizing radiation and its appropriateness for repeated evaluation. AIMS & METHODS: The aim of this study was to assess the role of MRE in evaluating Crohn's disease (CD) and its subsequent management strategies. The integrated hospital electronic database system reviewed retrospectively over a period of two years (Jan 2012- Dec 2013) and analysed for the following: clinical details, radiology, biochemistry, endoscopy and histology. RESULTS: MRE was performed in 69 patients (40 females and 29 males) with mean age of 35yeras (range 1679). Mean duration of illness was 6.32 years (range 0.5-37y). 7 (10%) patients were active smokers. Main indications for performing MRE were symptoms consistent with clinically active disease including abdominal pain, diarrhoea and weight loss and to exclude disease related complications. MRE showed radiological signs of active disease in 46 (66%) patients. MRE confirmed suspected Crohn's disease in eight out of twenty patients (40%) previously being treated as irritable bowel syndrome (IBS). In 28 (40%) patients MRE detected 37 complications (23 strictures, 11 fistulas and 3 abscesses) and was reported normal in 17/ 69 (24.6%) of cases. MRE redefined CD extent in 9 (13%) patients (6 colonic to ileo-colonic and 3 ileal to ileo-jejunal). MRE changed clinical management strategies in 38/69 (55%) patients. 10 (14.5%) were commenced on biologics (8 adalimumab & 2 infliximab); 8 (11.6%) changed to immunomodulators (6 azathioprine & one 6-mercaptopurine & methotrexate each); 3 (4.34%) patients commenced on combination therapy with infliximab and azathioprine and one prescribed budesonide. 15/69 (21.7%) patients had surgery; 3 right hemicolectomies; 4 small bowel resections; 3 strictureplasties; 3 fistula repairs; one colectomy and abscess drainage each and one endoscopic dilatation for small bowel stricture. CONCLUSION: Magnetic resonance enterography is highly useful in managing complex Crohn's disease. It is non-invasive and has no radiation related implications. In our experience it helped to detect disease related complications, redefined disease extent and activity. Particularly it changed clinical management strategies in more than 50% of patients. We recommend utilizing this diagnostic entity to achieve optimum treatment goals in selected cases.
Su1179 Differential Diagnosis of Polypoid Lesions of the Gallbladder Using ContrastEnhanced Ultrasonography With High Mechanical Index Contrast Mode Haruo Miwa, Kazushi Numata, Tomohiro Ishii, Takashi Kaneko, Wataru Shibata, Kazuya Sugimori, Katsuaki Tanaka, Shin Maeda Background and aim: Transabdominal ultrasonography is initially used to detect the polypoid lesions of the gallbladder (PLG); however, it is often difficult to characterize these lesions qualitatively. Contrast-enhanced ultrasonography (CEUS) with high mechanical index (HMI) contrast mode provides us vessel images in detail and we have reported that it was useful for the differential diagnosis of both hepatic and pancreatic lesions. In the present study, we aimed to evaluate the usefulness of CEUS with HMI contrast mode to differentiate PLG. Materials and methods: Between March 2007 and November 2014, 41 patients with PLG underwent CEUS with HMI contrast mode. They included 17 cases with gallbladder cancers, 19 cases with benign polyps, and 5 cases with gallbladder sludge. All cases with gallbladder cancer, 11 cases with benign polyp, and 2 cases with gallbladder sludge were confirmed by pathological results. The other 11 cases were diagnosed by radiological imaging followed up at least for one year. CEUS were performed, using the LOGIQ 7 ulatrasound imaging system (GE Healthcare, Milwaukee, WI) with perflubutane-based contrast agent, Sonazoid (Daiichi Sankyo, Tokyo, Japan). The coded harmonic angio mode (mechanical index = 0.60.9) was chosen for visualizing tumor vessels in detail. Vessel images of PLG were stored until 180 seconds from injection of Sonazoid and retrospectively reviewed by blinded readers. Institutional review board approved this study and informed consent was obtained from all patients. Results: The patients consisted of 24 male and 17 female, ranging in age from 31 to 80 years (mean, 65 years). The size of the lesions ranged from 10 mm to 47mm (mean, 19.5mm). All 5 cases of gallbladder sludges showed no vessel and the other 36 lesions had some type of vessels. The vessel form was categorized into 3 types, dotted vessel, branched vessel, and tortuous vessel. Gallbladder cancers included 14 cases (82%) with tortuous vessels and 3 cases (18%) with branched vessels. Benign polyps included 2 cases (11%) with tortuous vessels, 10 cases (51%) with branched vessels, and 7 cases (37%) with dotted vessels. Dilated vessels were detected in twelve cases (71%) of gallbladder cancer, but they were shown in only 1 case (5%) of benign polyp (p < 0.001). Pedunculated lesions were detected in 16 cases (84%) of benign polyps and 2 cases (12%) of gallbladder cancers (p < 0.001), those were clarified with a vessel flowing into the stalk of PLG. PLG with tortuous vessels or dilated vessels on CEUS with HMI contrast mode were diagnosed as gallbladder carcinomas. The sensitivity, specificity, and accuracy of this diagnosis were 89% (15/17), 92% (22/24), and 90% (37/41), respectively. Conclusion: Vessel images described by CEUS with HMI contrast mode are useful for differential diagnosis of PLG.
Su1182 EUS Guided Biliary Drainage Versus Percutaneous Transhepatic Biliary Drainage: Predictors of Successful Outcome in Patients Who Fail ERCP Reem Z. Sharaiha, Amit P. Desai, Ersilia M. DeFilippis, Sanjay Salgado, Jennifer E. Millman, Andrea M. Benvenuto, Monica Gaidhane, Amy Tyberg, Michel Kahaleh Background: Patients with biliary obstruction and concurrent co-morbidities, failed ampullary access, or altered anatomy have been conventionally offered percutaneous transhepatic biliary drainage (PTBD). While PTBD is effective, it carries risks such as catheter-related complications and chronic pain with poor quality of life. It is also contraindicated in patients with ascites and coagulopathy. There is limited data regarding the emerging role of endoscopic
S-429
AGA Abstracts
AGA Abstracts
Evaluation of Gastric Cancer Diagnosis Using Super Close Observation Endoscopy With Narrow-Band Imaging Takashi Kawai, Kyosuke Yanagisawa, Masakatsu Fukuzawa, Fuminori Moriyasu