- Email: [email protected]
Mo1061 A Comparison of Immunochemical Fecal Occult Blood Test and Total Colonoscopy in an Asymptomatic Population
Su2097
Inflammatory Bowel Diseases (IBD) were traditionally associated with weight loss. In recent years, there was a sharp increase in the number of overweight and obese IBD patients with metabolic syndrome phenotype. New evidence shows that adipokines produced by the expanded adipose tissue can regulate gut inflammation in patients with IBD. This complex interaction between metabolic abnormalities and inflammation in IBD patients has produced conflicting data. We sought to analyze the incidence of overweight and obesity in IBD patients and investigate the effect of insulin resistance on disease phenotype and outcome. Methods: A retrospective analysis was carried out in Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Patients were classified as being underweight, normal weight, overweight, or obese (BMI<18.5, 18.5-24.9, 25-29.9, ≥30 Kg/m2 respectively). We determined lipid profile and abdominal obesity (waist circumference ≥ 35" for women and ≥ 40" for men) for all patients. Based on fasting insulin resistance [HOMA-IR = fasting serum insulin (mmol/l) x fasting blood glucose (IU/ml) / 22.5] we divided the patients in two groups: insulin resistant (IR>3) and non-insulin resistant (IR<3). Montreal IBD classification was used to further divide the patients based on age of onset, disease location, and behavior. C-reactive protein (CRP) level was recorded as a biochemical measure of inflammation. For disease outcome we examined the need/number of surgical interventions, and rate of failure after immunomodulatory (Imuran/6MP) or biologic agents (Infliximab, Adalimumab, Certolizumab, Tysabri) therapies. Results: Forty seven percent (47%) of IBD patients were overweight and obese (28% & 19%, respectively) while only 3.7 % were underweight. The majority of overweight/obese patients were captured in the insulin resistance (IR>3) group with abnormal lipid profile (low HDL, high LDL, high triglycerides). Patients in both groups were rather young (median age interval 24-30 y) with no cardiovascular complications. In the group of overweight/obese patients with insulin resistance (IR>3) there was a significant shift toward colonic disease location in CD patients (none had small bowel disease alone) while pancolitis was prevalent in UC patients (all E3 in IR>3; no E3 in IR<3). CRP was significantly elevated in the IR>3 group and correlated with an inflammatory phenotype and more perianal disease as opposed to non-insulin resistant patients. Conclusions: Overweight and obese IBD patients with abnormal lipid profile and abdominal obesity are at high risk of developing insulin resistance and persistent inflammation that could complicate their disease outcome. Identifying patients with metabolic abnormalities early in the course of IBD could play an important role in the selection of effective immunomodulatory/biologic therapies and nutritional interventions
Su2096 Gluten Degrading Enzyme Effectively Digests Gluten in the Stomach and Small Intestine of Healthy Volunteers Bouke Salden, Veronica Monserrat, Freddy Troost, Maaike Bruins, Luppo Edens, Roger Bartholomé, Bjorn Winkens, Frits Koning, Ad Masclee A significant proportion of the population does not tolerate gluten. Aspergillus niger prolyl endopeptidase (AN-PEP) enzyme efficiently degrades gluten molecules into non-immunogenic peptides in a dynamic, multi-compartmental gastrointestinal simulation model but its efficacy in vivo remains to be established. Aim of our study was to assess the efficacy of ANPEP on gastrointestinal breakdown of gluten in healthy subjects, as well as the effect of meal caloric density on AN-PEP efficiency. Methods: In this double-blind, randomized, placebo-controlled cross-over study 12 healthy subjects attended to four test days in random order. On each occasion they received a low (143 kCal) or high caloric (405 kCal) meal, containing 4g gluten, with AN-PEP or placebo via a triple-lumen nasoduodenal catheter. Acetaminophen was added to measure gastric emptying rate. One lumen, positioned in the stomach, was used for administration of the test meal and collection of gastric fluid. A second lumen was used for the continuous injection of the inert dilution marker polyethylene glycol 3350 (PEG3350) to enable the calculation of meal dilution by endogenous secretions, with the injection port positioned just distal to the pylorus. A third lumen, located at the tube tip 10 cm distal to the second port, was used for collection of duodenal content. Fluid samples were taken regularly during 4 hours after meal infusion. The presence of the DQ2.5glia-α3 epitopes was quantified using the Gluten-Tec® ELISA assay, which provides an accurate estimate of the actual α-gliadin content of the samples. Degradation of intact gluten proteins was measured by Western-Blot analysis. Duodenal PEG3350 concentrations and gastric acetaminophen concentrations were determined by high-performance liquid chromatography. The effect of AN-PEP on gluten degradation was measured by the difference in 240-minute Area Under the Curve (AUC) of relative and absolute gluten exposure between AN-PEP and placebo. Differences between combinations of treatment and meal were assessed using linear mixed models. Results: AN-PEP significantly reduced gliadin concentration and absolute output in the stomach and duodenum (as 240-min AUCs) in both low and high caloric meals, compared to placebo. Furthermore, in the high caloric meal with placebo the duodenal gliadin concentration was lower, compared to the low caloric meal with placebo. No differences were observed between gliadin concentrations of a low or high caloric meal containing AN-PEP (Table). The gastric emptying time of the high caloric meal was longer compared to the low caloric meal, both in the presence of placebo (p=0.014) and AN-PEP (p=0.100). Conclusion: AN-PEP addition to a gluten containing meal significantly enhances gluten digestion in healthy volunteers. Meal caloric density does not affect the efficacy of AN-PEP on gluten degradation. Gliadin concentration and absolute output in stomach and duodenum
Mo1061 A Comparison of Immunochemical Fecal Occult Blood Test and Total Colonoscopy in an Asymptomatic Population Shinji Yoshii, Katsuhiro Mabe, Watano Keiko, Nobuaki Akakura, Mototsugu Kato Background: The results of the National Polyp Study suggested that endoscopic resection of all colorectal adenomatous polyps would contribute to the prevention of colorectal cancer.Use of the fecal occult blood test (FOBT) enables early detection of colorectal cancer, and there is evidence that the mortality rate of colorectal cancer can be reduced by using the FOBT. However, there has not been sufficient investigation of the association between the FOBT and colorectal adenomatous polyps. AIM: The aim of this study was to determine the usefulness of the immunochemical FOBT (iFOBT) for colorectal adenomatous polyps in an asymptomatic population. METHODS: From April 2004 to March 2012, 1281 asymptomatic individuals underwent a 2-day iFOBT, using a hemoplate auto L with a cut-off of 40 ng/ml buffer (or 40 ug/mg feces), and total colonoscopy (CS) simultaneously in a comprehensive health examination program in our hospital. Hyperplastic polyps in the recto-sigmoid colon were not included in the study. We divided the subjects into two groups, an iFOBT-positive group (iFOBT (+) group) and an iFOBT-negative group (iFOBT (-) group), and compared the characteristics of CS after iFOBT in the two groups. RESULTS: Of the 1281 examinees, 108 (8.4%) had a positive iFOBT result. There was no significant difference in age, gender,tumor morphology or tumor location between the two groups. The average tumor size (including adenoma% 10mm) in the iFOBT (+) group was significantly larger than that in the iFOBT (-) group (4.8 mm vs. 3.9 mm; P=0.02). Three of the 108 iFOBT (+) examinees showed advanced neoplasia (tubular adenoma ^10 mm, adenoma with villous histology, or high-grade dysplasia), while 11 of the 1173 iFOBT (-) examinees showed advanced neoplasia. The prevalence rate of advanced neoplasia was low and was not significantly different in the iFOBT (+) and iFOBT (-) groups (2.8% and 0.9%, respectively; P= 0.107). The prevalence rate of <10mm polyps was high in both groups without a significant difference (28.7% and 27.4%; P=0.735). CONCLUSION: The results suggest that iFOBT is inadequate as a screening test for detecting colorectal adenomatous polyps, especially subcentimetric polyps. Regardless of the results of iFOBT, subcentimetric polyps were detected in about 30% of the examinees. We recommend adding screening CS as an official optional method for preventing CRCs. Mo1062
Legend: * = LCM & placebo vs. LCM & AN-PEP; p < 0.001 # = HCM & placebo vs. HCM & AN-PEP; p < 0.001 ¥ = HCM & placebo vs. HCM & AN-PEP; p = 0.013 ^ = LCM & placebo vs. HCM & placebo; p = 0.001 && = below the limit of detection (7 ug*min/mL) & = below the limit of quantification (21 ug*min/mL)
Low Volume PEG and Adjunctive Neostigmine/Glycopyrrolate Improve Colonoscopic Bowel Preparation in Subjects With Spinal Cord Injury Mark A. Korsten, Christina Yen, Miroslav Radulovic, Alan S. Rosman, Kristel K. Hunt, Ann M. Spungen, Marinella D. Galea, Steven D. Kornfeld, William Bauman Background : Effective bowel preparation is essential for colon cancer screening spinal cord injury (SCI) patients frequently have suboptimal outcomes using standard, high volume PEG based bowel preparations (Colyte®). This has been attributed to difficulty with evacuation and altered colonic motility. It has previously been shown that bowel evacuation in these patients can be induced by the intravenous administration of neostigmine (a parasympathomimetic drug) in combination with glycopyrrolate (an anticholinergic agent) which blocks the non-GI side effects of neostigmine including bradycardia and bronchoconstriction. (AJG
S-545
AGA Abstracts
AGA Abstracts
Impact of Metabolic Syndrome on Inflammatory Bowel Disease Phenotype and Outcome Kenneth Obi, Violeta Arsenescu, Mohamed Naem, Razvan Arsenescu
Inflammatory Bowel Diseases (IBD) were traditionally associated with weight loss. In recent years, there was a sharp increase in the number of overweight and obese IBD patients with metabolic syndrome phenotype. New evidence shows that adipokines produced by the expanded adipose tissue can regulate gut inflammation in patients with IBD. This complex interaction between metabolic abnormalities and inflammation in IBD patients has produced conflicting data. We sought to analyze the incidence of overweight and obesity in IBD patients and investigate the effect of insulin resistance on disease phenotype and outcome. Methods: A retrospective analysis was carried out in Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Patients were classified as being underweight, normal weight, overweight, or obese (BMI<18.5, 18.5-24.9, 25-29.9, ≥30 Kg/m2 respectively). We determined lipid profile and abdominal obesity (waist circumference ≥ 35" for women and ≥ 40" for men) for all patients. Based on fasting insulin resistance [HOMA-IR = fasting serum insulin (mmol/l) x fasting blood glucose (IU/ml) / 22.5] we divided the patients in two groups: insulin resistant (IR>3) and non-insulin resistant (IR<3). Montreal IBD classification was used to further divide the patients based on age of onset, disease location, and behavior. C-reactive protein (CRP) level was recorded as a biochemical measure of inflammation. For disease outcome we examined the need/number of surgical interventions, and rate of failure after immunomodulatory (Imuran/6MP) or biologic agents (Infliximab, Adalimumab, Certolizumab, Tysabri) therapies. Results: Forty seven percent (47%) of IBD patients were overweight and obese (28% & 19%, respectively) while only 3.7 % were underweight. The majority of overweight/obese patients were captured in the insulin resistance (IR>3) group with abnormal lipid profile (low HDL, high LDL, high triglycerides). Patients in both groups were rather young (median age interval 24-30 y) with no cardiovascular complications. In the group of overweight/obese patients with insulin resistance (IR>3) there was a significant shift toward colonic disease location in CD patients (none had small bowel disease alone) while pancolitis was prevalent in UC patients (all E3 in IR>3; no E3 in IR<3). CRP was significantly elevated in the IR>3 group and correlated with an inflammatory phenotype and more perianal disease as opposed to non-insulin resistant patients. Conclusions: Overweight and obese IBD patients with abnormal lipid profile and abdominal obesity are at high risk of developing insulin resistance and persistent inflammation that could complicate their disease outcome. Identifying patients with metabolic abnormalities early in the course of IBD could play an important role in the selection of effective immunomodulatory/biologic therapies and nutritional interventions
Su2096 Gluten Degrading Enzyme Effectively Digests Gluten in the Stomach and Small Intestine of Healthy Volunteers Bouke Salden, Veronica Monserrat, Freddy Troost, Maaike Bruins, Luppo Edens, Roger Bartholomé, Bjorn Winkens, Frits Koning, Ad Masclee A significant proportion of the population does not tolerate gluten. Aspergillus niger prolyl endopeptidase (AN-PEP) enzyme efficiently degrades gluten molecules into non-immunogenic peptides in a dynamic, multi-compartmental gastrointestinal simulation model but its efficacy in vivo remains to be established. Aim of our study was to assess the efficacy of ANPEP on gastrointestinal breakdown of gluten in healthy subjects, as well as the effect of meal caloric density on AN-PEP efficiency. Methods: In this double-blind, randomized, placebo-controlled cross-over study 12 healthy subjects attended to four test days in random order. On each occasion they received a low (143 kCal) or high caloric (405 kCal) meal, containing 4g gluten, with AN-PEP or placebo via a triple-lumen nasoduodenal catheter. Acetaminophen was added to measure gastric emptying rate. One lumen, positioned in the stomach, was used for administration of the test meal and collection of gastric fluid. A second lumen was used for the continuous injection of the inert dilution marker polyethylene glycol 3350 (PEG3350) to enable the calculation of meal dilution by endogenous secretions, with the injection port positioned just distal to the pylorus. A third lumen, located at the tube tip 10 cm distal to the second port, was used for collection of duodenal content. Fluid samples were taken regularly during 4 hours after meal infusion. The presence of the DQ2.5glia-α3 epitopes was quantified using the Gluten-Tec® ELISA assay, which provides an accurate estimate of the actual α-gliadin content of the samples. Degradation of intact gluten proteins was measured by Western-Blot analysis. Duodenal PEG3350 concentrations and gastric acetaminophen concentrations were determined by high-performance liquid chromatography. The effect of AN-PEP on gluten degradation was measured by the difference in 240-minute Area Under the Curve (AUC) of relative and absolute gluten exposure between AN-PEP and placebo. Differences between combinations of treatment and meal were assessed using linear mixed models. Results: AN-PEP significantly reduced gliadin concentration and absolute output in the stomach and duodenum (as 240-min AUCs) in both low and high caloric meals, compared to placebo. Furthermore, in the high caloric meal with placebo the duodenal gliadin concentration was lower, compared to the low caloric meal with placebo. No differences were observed between gliadin concentrations of a low or high caloric meal containing AN-PEP (Table). The gastric emptying time of the high caloric meal was longer compared to the low caloric meal, both in the presence of placebo (p=0.014) and AN-PEP (p=0.100). Conclusion: AN-PEP addition to a gluten containing meal significantly enhances gluten digestion in healthy volunteers. Meal caloric density does not affect the efficacy of AN-PEP on gluten degradation. Gliadin concentration and absolute output in stomach and duodenum
Mo1061 A Comparison of Immunochemical Fecal Occult Blood Test and Total Colonoscopy in an Asymptomatic Population Shinji Yoshii, Katsuhiro Mabe, Watano Keiko, Nobuaki Akakura, Mototsugu Kato Background: The results of the National Polyp Study suggested that endoscopic resection of all colorectal adenomatous polyps would contribute to the prevention of colorectal cancer.Use of the fecal occult blood test (FOBT) enables early detection of colorectal cancer, and there is evidence that the mortality rate of colorectal cancer can be reduced by using the FOBT. However, there has not been sufficient investigation of the association between the FOBT and colorectal adenomatous polyps. AIM: The aim of this study was to determine the usefulness of the immunochemical FOBT (iFOBT) for colorectal adenomatous polyps in an asymptomatic population. METHODS: From April 2004 to March 2012, 1281 asymptomatic individuals underwent a 2-day iFOBT, using a hemoplate auto L with a cut-off of 40 ng/ml buffer (or 40 ug/mg feces), and total colonoscopy (CS) simultaneously in a comprehensive health examination program in our hospital. Hyperplastic polyps in the recto-sigmoid colon were not included in the study. We divided the subjects into two groups, an iFOBT-positive group (iFOBT (+) group) and an iFOBT-negative group (iFOBT (-) group), and compared the characteristics of CS after iFOBT in the two groups. RESULTS: Of the 1281 examinees, 108 (8.4%) had a positive iFOBT result. There was no significant difference in age, gender,tumor morphology or tumor location between the two groups. The average tumor size (including adenoma% 10mm) in the iFOBT (+) group was significantly larger than that in the iFOBT (-) group (4.8 mm vs. 3.9 mm; P=0.02). Three of the 108 iFOBT (+) examinees showed advanced neoplasia (tubular adenoma ^10 mm, adenoma with villous histology, or high-grade dysplasia), while 11 of the 1173 iFOBT (-) examinees showed advanced neoplasia. The prevalence rate of advanced neoplasia was low and was not significantly different in the iFOBT (+) and iFOBT (-) groups (2.8% and 0.9%, respectively; P= 0.107). The prevalence rate of <10mm polyps was high in both groups without a significant difference (28.7% and 27.4%; P=0.735). CONCLUSION: The results suggest that iFOBT is inadequate as a screening test for detecting colorectal adenomatous polyps, especially subcentimetric polyps. Regardless of the results of iFOBT, subcentimetric polyps were detected in about 30% of the examinees. We recommend adding screening CS as an official optional method for preventing CRCs. Mo1062
Legend: * = LCM & placebo vs. LCM & AN-PEP; p < 0.001 # = HCM & placebo vs. HCM & AN-PEP; p < 0.001 ¥ = HCM & placebo vs. HCM & AN-PEP; p = 0.013 ^ = LCM & placebo vs. HCM & placebo; p = 0.001 && = below the limit of detection (7 ug*min/mL) & = below the limit of quantification (21 ug*min/mL)
Low Volume PEG and Adjunctive Neostigmine/Glycopyrrolate Improve Colonoscopic Bowel Preparation in Subjects With Spinal Cord Injury Mark A. Korsten, Christina Yen, Miroslav Radulovic, Alan S. Rosman, Kristel K. Hunt, Ann M. Spungen, Marinella D. Galea, Steven D. Kornfeld, William Bauman Background : Effective bowel preparation is essential for colon cancer screening spinal cord injury (SCI) patients frequently have suboptimal outcomes using standard, high volume PEG based bowel preparations (Colyte®). This has been attributed to difficulty with evacuation and altered colonic motility. It has previously been shown that bowel evacuation in these patients can be induced by the intravenous administration of neostigmine (a parasympathomimetic drug) in combination with glycopyrrolate (an anticholinergic agent) which blocks the non-GI side effects of neostigmine including bradycardia and bronchoconstriction. (AJG
S-545
AGA Abstracts
AGA Abstracts
Impact of Metabolic Syndrome on Inflammatory Bowel Disease Phenotype and Outcome Kenneth Obi, Violeta Arsenescu, Mohamed Naem, Razvan Arsenescu