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Mo1351 Bypass of the Proximal Gut Has Weight Loss Independent Effects on Glycemic Control Dimitrios Pournaras, Erlend T. Aasheim, Ahmed R. Ahmed, David Mahon, Steve R. Bloom, Richard Welbourn, Torsten Olbers, Carel W. Le Roux Introduction The reported remission of type 2 diabetes in patients undergoing Roux-en-Y gastric bypass has brought the role of the gut in glucose metabolism in focus. We aimed to explore the role of the proximal gut on glucose handling. Methods A comparative controlled investigation of oral versus gastrostomy glucose loading in patients who had previously undergone gastric bypass and had a gastrostomy tube in the gastric remnant for feeding. A standard glucose load was administered either orally (day 1) or via the gastrostomy tube (day 2). Plasma levels of glucose, insulin, glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were measured pre and post glucose loading. Results Exclusion of the proximal small gut from glucose passage induced lower plasma glucose responses and higher plasma insulin, GLP-1 and PYY responses compared to glucose via a gastrostomy (p<0.05). Conclusions Exclusion of glucose passage through the proximal small gut results in enhanced insulin and gut hormone responses and suggests a weight loss independent effect explaining the improved glycaemic control after gastric bypass. The gut plays a central role in glucose metabolism and represents a target for future antidiabetes therapies. Mo1352 Multiple Factors Lead to a Low Referral Rate for Bariatric Surgery in an Urban Primary Care Setting Jonathan Z. Potack, Christopher Hogan, Elisabeth Kramer Introduction: Obesity is a major public health concern, contributing significantly to morbid- ity, mortality and healthcare spending. Non-surgical therapies (diet, exercise, medications) produce modest weight loss. Bariatric surgery is effective at treating obesity and its associated conditions. However despite clear benefits to surgery, referral rates for surgery are low in many primary care settings. We hypothesized that the referral rate for bariatric surgery is low in our center and sought to identify factors associated with this low rate. Methods: We devised a 16 question survey that evaluated: (1) provider knowledge and opinions of obesity treatment and (2) provider practices and referral patterns to bariatric surgery. It was distributed electronically to all medical housestaff and full time faculty in the Division of General Internal Medicine at the Mount Sinai School of Medicine. These physicians see patients in an urban primary care clinic. Responses were linked to providers' level of training but otherwise were confidential. Results: 81 physicians (51 housestaff, 26 faculty) and 4 nurse practitioners completed the survey. Response rates were 40% for housestaff and 62% for faculty. 89% of providers reported obesity rates of at least 25% in their practice including 41% of providers who report greater than 50% obesity rates. 74% of providers feel that weight plays a major role in the medical problems of at least half of their patients. However 40% of providers report spending less than 10% of the visit discussing obesity and 80% report a weight and a BMI are not recorded at every visit. Providers cited time constraints and need to address more pressing medical issues as the most common reasons more time was not spent discussing obesity. However 21% of providers feel their training in obesity is insufficient and less than 60% correctly identified appropriate referral criteria for bariatric surgery. (Figure 1) Furthermore while 90% of providers feel bariatric surgery is effective in the treatment of obesity, in the last year less than 10% referred more than 5 patients for bariatric surgery and only 3% reported more than 5 of their patients actually underwent bariatric surgery. (Figure 2) Reasons for this low referral rate include difficulty selecting appropriate candidates, patient disinterest, perceived surgical risk, and lack of knowledge as to how to refer a patient. Conclusions: Despite high levels of provider recognition of the importance of obesity as well as belief in the efficacy of bariatric surgery, there are multiple barriers to surgical referral yielding a low referral rate. Lack of time and structural issues of how to refer a patient are important. However, insufficient training in obesity is common and may contribute to low surgical referral rates. Improved obesity education may increase referral rates for bariatric surgery. Mo1353 Endoscopic Stent Placement as a Therapeutic Option for Post Bariatric Surgery Leaks: The Kuwait Experience Jaber Al-Ali, Adel Ahmed, Fahad Al-asfar, Basel Alsumait, Fuad Hasan Background Gastric leak after different types of bariatric surgeries is one of the most serious complications that can lead to death if not managed promptly. Revisional surgery for leaks is time consuming and associated with considerable morbidity. We report a series of cases with post sleeve gastrectomy and gastric bypass leaks that were successfully managed edos- copically by endoluminal stenting. Case Summary Sixteen patients (12 females and 2 males) with a post sleeve gastrectomey leaks and two (female) cases of leaks after gastro-jejunal bypass surgery were treated at Mubarak Al Kabeer Hospital, Kuwait with self- expandable partially covered metal stent (SEPCMS) (Ultraflex esophageal NG stent system, Boston Scientific.) to seal the leaks and CT-guided percutaneous drainage of intra-abdominal fluid collections . Fever and abdominal pain were the most common symptoms at the time of the presentation. Gastric leak was confirmed by fluoroscopic single-contrast (Visipaque 270) upper gastrointestinal study and/or CT-abdomen with oral contrast. Under fluoroscopic guidance the SEPCMS was inserted and kept in place for 6-8 weeks. All patients showed dramatic improvement of their symptoms with a decrease of draining amount. Oral feeding started 3-5 days after stenting. At week six, fully covered esophageal plastic stents (Polyflex esophageal stent, Boston Scientific) were deployed inside the SEPCMS to decrease the amount of granulation tissue. Both stents were removed successfully in all patients. One patient had esophageal mucosal tear that was treated endoscopically and one patient failed the endoscopic treatment and required gastric bypass surgery. Fifteen patients had a totally sealed leak. Conclusion Gastric leak after bariatric surgery is one of the most serious complication that need to be diagnosed and managed promptly. Endoluminal stenting to seal the leaking site S-619 AGA Abstracts is a viable, safe and minimally invasive therapeutic option in selected patients presenting with early or late gastric leaks. Mo1354 Reduced Calorie Intake and Weight Loss During Vagal Block (VBLOC Therapy) in Morbidly Obese Patients With Type 2 Diabetes Mellitus James Toouli, Nicholas H. Wray, Jane Collins, Adele Coles, Katherine S. Tweden, Lilian Kow Background: A medical device to treat morbid obesity that induces vagal block (VBLOC Therapy) through electrodes placed laparoscopically around both intra-abdominal vagal trunks has demonstrated clinically important weight loss in morbidly obese patients. Aim: To evaluate satiety and calorie intake at baseline and during 6 months of VBLOC Therapy in obese patients with type 2 diabetes mellitus that were implanted with the Maestro RC2 System. Method: Ten patients (6 females; age: 51.5±3.1; BMI: 37.5±0.7 kg/m2) were implanted at one center and received VBLOC Therapy for 6 months. Follow-up included body weights; 7-day diet records assessed by a nutritionist; calorie calculations; and, visual analogue scale (VAS) questions to assess satiety by 7-day or 24-hour recall at the following time periods: baseline, 4 and 12 weeks and 6 months post device initiation. A validated program, Food WorksTM, was used to determine calorie and nutrition content. Data are presented as mean±SE. Results: Mean EWL at 6 months was 33±5%, p<0.001. Calorie intake decreased by 45% (p<.001), 48% (p<.001) and 37% (p=.02), respectively, at 4 and 12 weeks and 6 months from a baseline of 2062 kcal/day. VAS recall data, using a repeated measures analysis, documented fullness at the beginning of meals (p=.006) and less food consumption (p=.02) corroborating the reduction in caloric intake. Conclusion: During 6 months of VBLOC therapy, obese patients with type 2 diabetes achieved a mean EWL >33%, reduced their caloric consumption by >35% and also experienced enhanced satiety. Mo1355 Intestinal Mucosal Mast Cells is Activated by Fat Absorption Yong Ji, Yasuhisa Sakata, Qing Yang, Patrick Tso Background. There are increasing evidences showing that gut mucosal immune system not only plays a key role in the modulation of local inflammatory events but is also associated with fat intake. Aim: The aim of this study was to determine if fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Methods: Conscious intestinal lymph fistula rats were used for the study. The mesenteric lymph ducts were cannulated in anesthetized rats for the collection of intestinal lymph. An infusion tube was installed in the duodenum for the infusion of nutrients. Lymphatic levels during fasting and also during active fat absorption of the preformed MMC mediators including histamine and rat MMC protease II (RMCPII), as well as the newly synthesized mediators such as prostaglandin D2 (PGD2), interleukin-6 (IL-6), and monocyte chemotract- ant protein (MCP-1) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescence staining of the jejunum sections with mono-specific antibodies against RMCPII after lipid infusion. Results: Intraduodenal infusion of Liposyn II 20 % (4.43 kcal/3ml) dramatically increased the lymphatic concentrations of histamine by one fold and RMCPII, a specific marker of rat intestinal MMC degranulation, by ~20 fold peaking at 1 hour and returning to fasting level by 3 h after infusion. There were no significant increase in lymphatic histamine nor RMCPII after infusion with isocaloric and isovolume Dextrin or Whey protein, suggesting that the activation of MMC by fat absorption is specific and not shared by the absorption of protein or carbohydrate. Furthermore, the stimulation of secretion of RMCPII by Liposyn II 20 % is dose dependent (0.55kCal, 1.1 kCal, 2.2 kCal and 4.4 kCal induced the following increases in lymphatic concentration of RMCPII 3.48±0.38, 4.39±0.69, 11.89±0.59 and 20.28±0.98 fold over saline, respectively), illustrating a close dose-dependent relationship between the amount of lipid infused and the degree of MMC activation. Measurement of lymphatic PGD2, IL-6 and MCP-1, showed significant increases by 1.01 fold, 1.76 fold and 0.84 fold, respectively, peaking at 2-3 h after the beginning of Liposyn II infusion. Immunofluorescent staining of the rat jejunum taken at 1 hour after Liposyn II infusion revealed the degranulation of MMC in the lamina propria. Conclusion: In conscious lymph fistula rats, we have demonstrated for the first time that the intestinal MMC are activated by fat absorption and this result in the release of numerous mast cell mediators into intestinal lymph. Although the role of intestinal MMC has been well defined in diseased conditions such as anaphylaxis, food allergy and inflammatory bowel disease, the physiological function of MMC in fat absorption is not clear and warrants further studies. Mo1657 Acidic Bile Salt Modulates the Squamous Epithelial Barrier Function by Modulating Tight Junction Protein Xin Chen, Tadayuki Oshima, Toshihiko Tomita, Hirokazu Fukui, Jiro Watari, Takayuki Matsumoto, Hiroto Miwa Background: Experimental models for esophageal epithelium In Vitro are either suffering from poor differentiation or a complicated culture system. We have previously reported that air-liquid interface (ALI) system with normal human bronchial epithelial (NHBE) cells can be a model of esophageal like squamous epithelial cell layers In Vitro. (DDW2010 1061 Research Forum). Here we explore the influence of acid and bile acid on barrier function and tight junction proteins with this system. Methods: NHBE cells were used in this study. Cells were seeded onto collagen and fibronectin coated trans-well inserts. Culture at ALI conditions was initiated by removing the medium on the apical side, while keeping the insert in contact with medium on the basal side and the culture was continued for 10 days. Tthe cells were treated with pH 7.4 or 3.0 medium with taurocholic acid (TCA), glycocholic acid (GCA) and deoxycholic acid (DCA) from apical side for up to 1 hour. The influence of pepsin was also examined at pH3 acidic condition. Barrier function was measured by trans-epithelial electrical resistance (TEER) and diffusion of paracellular tracers. Tight junc- tion protein including claudin-1, cluadin-4 and occuldin expression and localization was AGA Abstracts

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Mo1351

Bypass of the Proximal Gut Has Weight Loss Independent Effects on GlycemicControlDimitrios Pournaras, Erlend T. Aasheim, Ahmed R. Ahmed, David Mahon, Steve R.Bloom, Richard Welbourn, Torsten Olbers, Carel W. Le Roux

Introduction The reported remission of type 2 diabetes in patients undergoing Roux-en-Ygastric bypass has brought the role of the gut in glucose metabolism in focus. We aimedto explore the role of the proximal gut on glucose handling.Methods A comparative controlledinvestigation of oral versus gastrostomy glucose loading in patients who had previouslyundergone gastric bypass and had a gastrostomy tube in the gastric remnant for feeding. Astandard glucose load was administered either orally (day 1) or via the gastrostomy tube(day 2). Plasma levels of glucose, insulin, glucagon-like peptide 1 (GLP-1) and peptide YY(PYY) were measured pre and post glucose loading. Results Exclusion of the proximal smallgut from glucose passage induced lower plasma glucose responses and higher plasma insulin,GLP-1 and PYY responses compared to glucose via a gastrostomy (p<0.05). ConclusionsExclusion of glucose passage through the proximal small gut results in enhanced insulinand gut hormone responses and suggests a weight loss independent effect explaining theimproved glycaemic control after gastric bypass. The gut plays a central role in glucosemetabolism and represents a target for future antidiabetes therapies.

Mo1352

Multiple Factors Lead to a Low Referral Rate for Bariatric Surgery in anUrban Primary Care SettingJonathan Z. Potack, Christopher Hogan, Elisabeth Kramer

Introduction: Obesity is a major public health concern, contributing significantly to morbid-ity, mortality and healthcare spending. Non-surgical therapies (diet, exercise, medications)produce modest weight loss. Bariatric surgery is effective at treating obesity and its associatedconditions. However despite clear benefits to surgery, referral rates for surgery are low inmany primary care settings. We hypothesized that the referral rate for bariatric surgery islow in our center and sought to identify factors associated with this low rate. Methods: Wedevised a 16 question survey that evaluated: (1) provider knowledge and opinions ofobesity treatment and (2) provider practices and referral patterns to bariatric surgery. It wasdistributed electronically to all medical housestaff and full time faculty in the Division ofGeneral Internal Medicine at the Mount Sinai School of Medicine. These physicians seepatients in an urban primary care clinic. Responses were linked to providers' level of trainingbut otherwise were confidential. Results: 81 physicians (51 housestaff, 26 faculty) and 4nurse practitioners completed the survey. Response rates were 40% for housestaff and 62%for faculty. 89% of providers reported obesity rates of at least 25% in their practice including41% of providers who report greater than 50% obesity rates. 74% of providers feel thatweight plays a major role in the medical problems of at least half of their patients. However40% of providers report spending less than 10% of the visit discussing obesity and 80%report a weight and a BMI are not recorded at every visit. Providers cited time constraintsand need to address more pressing medical issues as the most common reasons more timewas not spent discussing obesity. However 21% of providers feel their training in obesityis insufficient and less than 60% correctly identified appropriate referral criteria for bariatricsurgery. (Figure 1) Furthermore while 90% of providers feel bariatric surgery is effective inthe treatment of obesity, in the last year less than 10% referred more than 5 patients forbariatric surgery and only 3% reported more than 5 of their patients actually underwentbariatric surgery. (Figure 2) Reasons for this low referral rate include difficulty selectingappropriate candidates, patient disinterest, perceived surgical risk, and lack of knowledgeas to how to refer a patient. Conclusions: Despite high levels of provider recognition of theimportance of obesity as well as belief in the efficacy of bariatric surgery, there are multiplebarriers to surgical referral yielding a low referral rate. Lack of time and structural issuesof how to refer a patient are important. However, insufficient training in obesity is commonand may contribute to low surgical referral rates. Improved obesity education may increasereferral rates for bariatric surgery.

Mo1353

Endoscopic Stent Placement as a Therapeutic Option for Post BariatricSurgery Leaks: The Kuwait ExperienceJaber Al-Ali, Adel Ahmed, Fahad Al-asfar, Basel Alsumait, Fuad Hasan

Background Gastric leak after different types of bariatric surgeries is one of the most seriouscomplications that can lead to death if not managed promptly. Revisional surgery for leaksis time consuming and associated with considerable morbidity. We report a series of caseswith post sleeve gastrectomy and gastric bypass leaks that were successfully managed edos-copically by endoluminal stenting. Case Summary Sixteen patients (12 females and 2 males)with a post sleeve gastrectomey leaks and two (female) cases of leaks after gastro-jejunalbypass surgery were treated at Mubarak Al Kabeer Hospital, Kuwait with self- expandablepartially covered metal stent (SEPCMS) (Ultraflex esophageal NG stent system, BostonScientific.) to seal the leaks and CT-guided percutaneous drainage of intra-abdominal fluidcollections . Fever and abdominal pain were the most common symptoms at the time ofthe presentation. Gastric leak was confirmed by fluoroscopic single-contrast (Visipaque 270)upper gastrointestinal study and/or CT-abdomen with oral contrast. Under fluoroscopicguidance the SEPCMS was inserted and kept in place for 6-8 weeks. All patients showeddramatic improvement of their symptoms with a decrease of draining amount. Oral feedingstarted 3-5 days after stenting. At week six, fully covered esophageal plastic stents (Polyflexesophageal stent, Boston Scientific) were deployed inside the SEPCMS to decrease the amountof granulation tissue. Both stents were removed successfully in all patients. One patient hadesophageal mucosal tear that was treated endoscopically and one patient failed the endoscopictreatment and required gastric bypass surgery. Fifteen patients had a totally sealed leak.Conclusion Gastric leak after bariatric surgery is one of the most serious complication thatneed to be diagnosed and managed promptly. Endoluminal stenting to seal the leaking site

S-619 AGA Abstracts

is a viable, safe and minimally invasive therapeutic option in selected patients presentingwith early or late gastric leaks.

Mo1354

Reduced Calorie Intake and Weight Loss During Vagal Block (VBLOCTherapy) in Morbidly Obese Patients With Type 2 Diabetes MellitusJames Toouli, Nicholas H. Wray, Jane Collins, Adele Coles, Katherine S. Tweden, LilianKow

Background: A medical device to treat morbid obesity that induces vagal block (VBLOCTherapy) through electrodes placed laparoscopically around both intra-abdominal vagaltrunks has demonstrated clinically important weight loss in morbidly obese patients. Aim:To evaluate satiety and calorie intake at baseline and during 6 months of VBLOC Therapyin obese patients with type 2 diabetes mellitus that were implanted with the Maestro RC2System. Method: Ten patients (6 females; age: 51.5±3.1; BMI: 37.5±0.7 kg/m2) wereimplanted at one center and received VBLOC Therapy for 6 months. Follow-up includedbody weights; 7-day diet records assessed by a nutritionist; calorie calculations; and, visualanalogue scale (VAS) questions to assess satiety by 7-day or 24-hour recall at the followingtime periods: baseline, 4 and 12 weeks and 6 months post device initiation. A validatedprogram, Food WorksTM, was used to determine calorie and nutrition content. Data arepresented as mean±SE. Results: Mean EWL at 6 months was 33±5%, p<0.001. Calorie intakedecreased by 45% (p<.001), 48% (p<.001) and 37% (p=.02), respectively, at 4 and 12weeks and 6 months from a baseline of 2062 kcal/day. VAS recall data, using a repeatedmeasures analysis, documented fullness at the beginning of meals (p=.006) and less foodconsumption (p=.02) corroborating the reduction in caloric intake. Conclusion: During 6months of VBLOC therapy, obese patients with type 2 diabetes achieved a mean EWL >33%,reduced their caloric consumption by >35% and also experienced enhanced satiety.

Mo1355

Intestinal Mucosal Mast Cells is Activated by Fat AbsorptionYong Ji, Yasuhisa Sakata, Qing Yang, Patrick Tso

Background. There are increasing evidences showing that gut mucosal immune system notonly plays a key role in the modulation of local inflammatory events but is also associatedwith fat intake. Aim: The aim of this study was to determine if fat absorption activatesintestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system.Methods: Conscious intestinal lymph fistula rats were used for the study. The mesentericlymph ducts were cannulated in anesthetized rats for the collection of intestinal lymph. Aninfusion tube was installed in the duodenum for the infusion of nutrients. Lymphatic levelsduring fasting and also during active fat absorption of the preformed MMC mediatorsincluding histamine and rat MMC protease II (RMCPII), as well as the newly synthesizedmediators such as prostaglandin D2 (PGD2), interleukin-6 (IL-6), and monocyte chemotract-ant protein (MCP-1) were measured by ELISA. Intestinal MMC degranulation was visualizedby immunofluorescence staining of the jejunum sections with mono-specific antibodiesagainst RMCPII after lipid infusion. Results: Intraduodenal infusion of Liposyn II 20 % (4.43kcal/3ml) dramatically increased the lymphatic concentrations of histamine by one fold andRMCPII, a specific marker of rat intestinal MMC degranulation, by ~20 fold peaking at 1hour and returning to fasting level by 3 h after infusion. There were no significant increasein lymphatic histamine nor RMCPII after infusion with isocaloric and isovolume Dextrin orWhey protein, suggesting that the activation of MMC by fat absorption is specific and notshared by the absorption of protein or carbohydrate. Furthermore, the stimulation of secretionof RMCPII by Liposyn II 20 % is dose dependent (0.55kCal, 1.1 kCal, 2.2 kCal and 4.4kCal induced the following increases in lymphatic concentration of RMCPII 3.48±0.38,4.39±0.69, 11.89±0.59 and 20.28±0.98 fold over saline, respectively), illustrating a closedose-dependent relationship between the amount of lipid infused and the degree of MMCactivation. Measurement of lymphatic PGD2, IL-6 and MCP-1, showed significant increasesby 1.01 fold, 1.76 fold and 0.84 fold, respectively, peaking at 2-3 h after the beginning ofLiposyn II infusion. Immunofluorescent staining of the rat jejunum taken at 1 hour afterLiposyn II infusion revealed the degranulation of MMC in the lamina propria. Conclusion:In conscious lymph fistula rats, we have demonstrated for the first time that the intestinalMMC are activated by fat absorption and this result in the release of numerous mast cellmediators into intestinal lymph. Although the role of intestinal MMC has been well definedin diseased conditions such as anaphylaxis, food allergy and inflammatory bowel disease,the physiological function of MMC in fat absorption is not clear and warrants further studies.

Mo1657

Acidic Bile Salt Modulates the Squamous Epithelial Barrier Function byModulating Tight Junction ProteinXin Chen, Tadayuki Oshima, Toshihiko Tomita, Hirokazu Fukui, Jiro Watari, TakayukiMatsumoto, Hiroto Miwa

Background: Experimental models for esophageal epithelium In Vitro are either sufferingfrom poor differentiation or a complicated culture system. We have previously reported thatair-liquid interface (ALI) system with normal human bronchial epithelial (NHBE) cells canbe a model of esophageal like squamous epithelial cell layers In Vitro. (DDW2010 1061Research Forum). Here we explore the influence of acid and bile acid on barrier functionand tight junction proteins with this system. Methods: NHBE cells were used in this study.Cells were seeded onto collagen and fibronectin coated trans-well inserts. Culture at ALIconditions was initiated by removing the medium on the apical side, while keeping theinsert in contact with medium on the basal side and the culture was continued for 10 days.Tthe cells were treated with pH 7.4 or 3.0 medium with taurocholic acid (TCA), glycocholicacid (GCA) and deoxycholic acid (DCA) from apical side for up to 1 hour. The influenceof pepsin was also examined at pH3 acidic condition. Barrier function was measured bytrans-epithelial electrical resistance (TEER) and diffusion of paracellular tracers. Tight junc-tion protein including claudin-1, cluadin-4 and occuldin expression and localization was

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