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Su1185 Characterization of Three Novel Enteropathies in Children With Unexplained Protracted Diarrhea
AGA Abstracts
Doctor abstracted the medical records using a preform including comorbidities, drugs, and history of fecal impaction. A minimental test (Folstein test), a test of functional abilities (Barthel test), and a rectal examination were also performed. Constipation was defined according to medical records and adequate/inadequate control was defined according to the reporting of constipation symptoms in symptoms' questionnaire. Fecal impaction was defined as the presence of a hard mass of feces in the rectum that the subject was unable to defecate by itself. Physician diagnosis of fecal impaction was the dependent variable for the analysis of associated factors using multiple logistic regression. Results.21 of the 34 invited nursing homes participated in the study (61%) and included 488 residents; no relevant differences were found between this sample and the pilot study sample, so they were pooled (N=687). The annual prevalence of fecal impaction was 47.3%; (95%CI: 43.6-51.0%) according to medical diagnosis, 57.9%; (95%CI: 54.2-61.6%) according to self-report, and 6.6% (95%CI:4.7-8.5%) according to rectal examination. Factors independently associated with fecal impaction according to medical diagnosis were controlled constipation (aOR9.8 (5.218.4), non-controlled constipation (aOR 37.2 (19.7- 70.4), decrease functional abilities (Barthel's score) (aOR 0.98 (0.97-0.99) and occasional use of NSAID (aOR 2.3 (1.2- 4.5). Conclusion. Annual prevalence of fecal impaction in nursing homes is around 50% and 6.6% of residents are impacted if a rectal examination is done. Main factors independently associated with impaction are constipation, low functional abilities, and occasional use of NSAIDS.
intestine were found in GK rats; however the afferents adaptation caused by stress-relaxation and creep did not changed. The observed changes may be related to the muscle layer remodeling and a contributing factor and mechanism to the gastrointestinal symptoms experienced by diabetic patients. Key words: Afferents, Spike rate, Stress-strain, Creep, Stress-relaxation, Small intestine, Type 2 diabetes Su1187 Microscopic Colitis-More Interesting Than Irritating in the Post Budesonide Era Aoibhlinn M. O'Toole, Alan Coss, Grainne Holleran, Denise Keegan, Kieran Sheahan, Glen A. Doherty, Diarmuid P. O'Donoghue, Hugh Mulcahy Background: Microscopic colitis is a common cause of chronic watery diarrhoea. However, many aspects regarding aetiology, pathogenesis and natural history remain poorly understood. The aim of this study is to report a single centre experience with this condition. Methods: 222 patients (52 male, 170 female; median age 64 years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes were reviewed and data on age, gender, clinical features, history of autoimmune diseases, medication use, cigarette smoking, histology and outcome were collected. Results: There were 99 cases of lymphocytic and 123 of collagenous colitis. Diarrhoea was almost invariably present (98%) while abdominal pain (24%), weight loss (10%), faecal incontinence (8%) and blood PR (5%) were also described. 28% had concomitant autoimmune diseases, most commonly celiac disease. Patients were taking a variety of medicationsat diagnosis thought to be associated with microscopic colitis including NSAIDs (22%), aspirin (19%), statins (15%), proton pump inhibitors (19%) and SSRIs (10%) at diagnosis. Prior to the widespread use of budesonide in our institution, 33% of patients required two or more medications during therapy compared to 15% following the introduction of budesonide (p=0.001). 38% of patients achieved spontaneous remission with either no treatment or simple antidiarrhoeals. An additional 50% responded to a variety of therapies, most commonly budesonide, while 12% did not achieve clinical remission. Using a multivariate model, the only factor associated with spontaneous remission was male gender (RR 1.9; 95% CI 1.0-3.6; p=0.04). Overall, the prognosis was excellent. There were no deaths attributable to microscopic colitis, while only 3 patients required immunomodulator therapy (all pre-budesonide era). One further patient underwent a colectomy because of intractable diarrhoea prior to the introduction of budesonide. Conclusion: Microscopic colitis is predominantly a benign and self-limiting disorder. The introduction of budesonide has revolutionised treatment and rendered the disease more interesting than irritating.
Su1185 Characterization of Three Novel Enteropathies in Children With Unexplained Protracted Diarrhea Sergei Tatishchev, Martin G. Martin, Galen Cortina Background: Neonatal diarrhea may be due to congenital enteropathies; a subset of which is diagnosed by careful microscopic exam of small bowel mucosa. Three structural epithelial defects dominate this diagnostic category: microvillus inclusion disease (MVID), tufting enteropathy (TE) and enteroendocrine cell dysgenesis (ECD). These are distinguished from congenital enteropathies that are morphologically normal but are typically due to defective transport protein and digestive enzymes. These 3 dominant structural epithelial defects are diagnosed by routine H&E microscopy, immunohistochemistry and electron microscopy, but they have all been genetically characterized. We have found that the morphological approach can still identify subtle structural epithelial defects responsible for congenital diarrhea, and as such, distinguish them from morphologically normal mucosa. Aims: To illustrate that focused careful morphological exam of gastrointestinal mucosal biopsies with intact architecture ultimately reveals structural epithelial defect(s) responsible for more enteropathies than MVID, TE and ECD. Methods: Gastrointestinal mucosal biopsies from 3 pediatric patients (ages 2 - 40 months) with early-onset chronic unexplained diarrhea were studied using H&E, immunohistochemistry and electron microscopy. In addition, patients' DNA samples were partly characterized using Sanger sequencing and comparative genomic hybridization. Results: Three new enteropathies were identified in young children with intact mucosal architecture and preserved absorptive epithelial cells. All three patients showed loss of various secretory cells. Patient 1 (6 months old) born to a consanguineous couple shows loss of endocrine serotonin-secreting cells in gastric, duodenal and colonic biopsies. Comparative genome hybridization identified a defective prohormone convertase 1 gene. Patient 2 (2 months old) with Dandy-Walker malformation has absence of goblet, Paneth and endocrine cells in duodenal and rectal biopsies, absent CDX-2 expression and normal CDX-2 and HATH 1 genes by Sanger sequencing. Patient 3 (40 month old) with Zn-deficiency and repeated infections has loss of Paneth cells in duodenal biopsies; genetic studies are incomplete at this time. Conclusions: Herein we presented the morphologic description of three novel enteropathies based on epithelial defects. By using a combination of H&E and immunohistochemical studies we have identified patients with absence of 1) secretory epithelial cells, 2) enterochromaffin cells and 3) Paneth cells. This approach reinforces the principle that new congenital abnormalities with intact mucosal architecture can be identified through a careful morphologic examination.
Su1188 Serum Anti Sacromyces Cervecedes Antibody IgA (ASCA IgA) is a Novel Surrogate for Marker of Small Intestinal Bacterial Overgrowth (SIBO)-a Randomized Open Label Control Prospective Pilot Trial Patrick Basu, Thankam Nair, Mikram Jafri, Sakina Farhat, Sajith Foustin, Kavya Mittimani, Lynn P. Ang, Niraj James Shah Objectives:Small Intestinal bacterial overgrowth is a common clinical entity. Diagnostic aids are challenging without wide range of availability. ASCA IgA,IgG has been established for inflammatory Bowel Disease (IBD). This study evaluates the utility of ASCA IgA in SIBO. Methods; Hundred twenty (n=120) patients were recruited and divided into three groups: Group A (n=40) control, Group B (n=50) breath test positive,ASCA IgA positive, IgG negative and Group C (n= 30) Chron's disease in remission. All underwent pre and post Serum ASCA IgA and IgG ,AMCA,ALCA, ACCA, OMPC, Anti CHBR antibody, CRP, Breath testing and Colonoscopy with Ileal biopsy.SIBO positive subjects were given Xifaxan 550mg twice daily for 14 days. Exclusion: Celiac disease, Parasitic infestation, End stage liver, GI Tract malignancy, recent anti bacterial use. Results: In Group A, 3/40(7%) false positive ASCA IgA, rest of the antibodies were negative. Breath test positive 2/40 (5%). Post therapy 2/ 40(5%) ASCA IgA and breath test 2/40 (5%) remained positive. Group B post therapy 44/ 50(88%) Breath test Negative and 47/50 (94%) ASCA IgA negative. False positive breath test 6/50(12%) and ASCA IgA 3/50(6%). Group B rest of the Antibodies all negative pre and post except 2/50(4%)False positives AMCA and 1/50 '(2%) ALCA false positives. Group C Biopsy, ASCA IgA IgG positive ,breath test [ pre 3/30(10%) post 2/30(6%)] ASCA IgA ( false Negative ) 3/30( 10%) Summary:ASCA IgA is simple, Non Operator dependent, easily available in all the labrotaries,Inexpensive, relevant specific serum marker for SIBO. Larger study needs to validate. Table 1
Su1186 Mechano-Sensory Properties of Diabetic Intestine in Goto-Kakizaki Rats Jian Yang, Jingbo Zhao, Hans Gregersen Background: Up to 75% of diabetic patients have experience with gastrointestinal symptoms such as nausea, bloating, abdominal pain, diarrhea, constipation etc. but the pathogenesis is not well understood. Only few studies have addressed the sensory function where most studies were evaluated from central nerve system. However, the peripheral afferent nerves may likely be involved due to the complexity of gastrointestinal regulation and the enteric nervous system. In this study we investigated the afferent nerve trafficking from jejunum in a Go-Kakizaki (GK) type-2 diabetic rat model. Methods: Seven 32 weeks old male GK rats and seven age-matched normal Wistar rats were used. Afferent nerve activity was recorded under various mechanical stimulations in excised jejunal segments: 1) ramp test up to 60mmHg with two distension rates, 2) relaxation tests and 3) creep test with initial pressures of 20mmHg or 40mmHg lasting 300 seconds. The mechanical circumferential stress and strain were computed. The spike rate increase ratio (SRIR) was calculated for evaluation of nerve activity during the mechanical stimulation. The association between SRIR and muscle layer thickness were also analyzed. Results: At the termination of the experiment, the glucose levels were elevated in GK rats by 41%. Intestinal circumferential muscle layer thickness in diabetic GK rats was significantly thicker than that of normal controls. The stress-strain relationships showed no difference between groups. Elevated sensitivity to mechanical stimuli was found both for the SRIR-stress and SRIR-strain relationships (Figure 1, P<0.05). In the stress relaxation test, stress relaxed less in the diabetic than in the normal group (44.4% vs 64.8% in 20mmHg relaxation, 62.4% vs 76% in 40 mmHg relaxation, P<0.05). However, the normalized spike rate as function of time did not differ between normal and GK rats (P>0.05). In the creep test, no significant difference was found for either normalized strain or normalized spike rate between two groups. The linear association between SRIR and the thickness of circumferential muscle layer was found (Figure 2). Conclusion: Altered viscoelastic properties and elevated mechano-sensitivity in the small
AGA Abstracts
Su1189 Identification of Cardinal Symptoms in Patients With Chronic Idiopathic Constipation (CIC) Alan Joslyn, Laura Barrow, Gary Jacob, Jean Paty Plecanatide, a guanylate cyclase C agonist, is currently under clinical development for the treatment of CICAs part of the clinical evaluation of plecanatide, we undertook development of an instrument to collect Patient Reported Outcomes (PRO) on a daily basis. The purpose was to collect efficacy data for symptom-based secondary efficacy endpoints in support of
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Doctor abstracted the medical records using a preform including comorbidities, drugs, and history of fecal impaction. A minimental test (Folstein test), a test of functional abilities (Barthel test), and a rectal examination were also performed. Constipation was defined according to medical records and adequate/inadequate control was defined according to the reporting of constipation symptoms in symptoms' questionnaire. Fecal impaction was defined as the presence of a hard mass of feces in the rectum that the subject was unable to defecate by itself. Physician diagnosis of fecal impaction was the dependent variable for the analysis of associated factors using multiple logistic regression. Results.21 of the 34 invited nursing homes participated in the study (61%) and included 488 residents; no relevant differences were found between this sample and the pilot study sample, so they were pooled (N=687). The annual prevalence of fecal impaction was 47.3%; (95%CI: 43.6-51.0%) according to medical diagnosis, 57.9%; (95%CI: 54.2-61.6%) according to self-report, and 6.6% (95%CI:4.7-8.5%) according to rectal examination. Factors independently associated with fecal impaction according to medical diagnosis were controlled constipation (aOR9.8 (5.218.4), non-controlled constipation (aOR 37.2 (19.7- 70.4), decrease functional abilities (Barthel's score) (aOR 0.98 (0.97-0.99) and occasional use of NSAID (aOR 2.3 (1.2- 4.5). Conclusion. Annual prevalence of fecal impaction in nursing homes is around 50% and 6.6% of residents are impacted if a rectal examination is done. Main factors independently associated with impaction are constipation, low functional abilities, and occasional use of NSAIDS.
intestine were found in GK rats; however the afferents adaptation caused by stress-relaxation and creep did not changed. The observed changes may be related to the muscle layer remodeling and a contributing factor and mechanism to the gastrointestinal symptoms experienced by diabetic patients. Key words: Afferents, Spike rate, Stress-strain, Creep, Stress-relaxation, Small intestine, Type 2 diabetes Su1187 Microscopic Colitis-More Interesting Than Irritating in the Post Budesonide Era Aoibhlinn M. O'Toole, Alan Coss, Grainne Holleran, Denise Keegan, Kieran Sheahan, Glen A. Doherty, Diarmuid P. O'Donoghue, Hugh Mulcahy Background: Microscopic colitis is a common cause of chronic watery diarrhoea. However, many aspects regarding aetiology, pathogenesis and natural history remain poorly understood. The aim of this study is to report a single centre experience with this condition. Methods: 222 patients (52 male, 170 female; median age 64 years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes were reviewed and data on age, gender, clinical features, history of autoimmune diseases, medication use, cigarette smoking, histology and outcome were collected. Results: There were 99 cases of lymphocytic and 123 of collagenous colitis. Diarrhoea was almost invariably present (98%) while abdominal pain (24%), weight loss (10%), faecal incontinence (8%) and blood PR (5%) were also described. 28% had concomitant autoimmune diseases, most commonly celiac disease. Patients were taking a variety of medicationsat diagnosis thought to be associated with microscopic colitis including NSAIDs (22%), aspirin (19%), statins (15%), proton pump inhibitors (19%) and SSRIs (10%) at diagnosis. Prior to the widespread use of budesonide in our institution, 33% of patients required two or more medications during therapy compared to 15% following the introduction of budesonide (p=0.001). 38% of patients achieved spontaneous remission with either no treatment or simple antidiarrhoeals. An additional 50% responded to a variety of therapies, most commonly budesonide, while 12% did not achieve clinical remission. Using a multivariate model, the only factor associated with spontaneous remission was male gender (RR 1.9; 95% CI 1.0-3.6; p=0.04). Overall, the prognosis was excellent. There were no deaths attributable to microscopic colitis, while only 3 patients required immunomodulator therapy (all pre-budesonide era). One further patient underwent a colectomy because of intractable diarrhoea prior to the introduction of budesonide. Conclusion: Microscopic colitis is predominantly a benign and self-limiting disorder. The introduction of budesonide has revolutionised treatment and rendered the disease more interesting than irritating.
Su1185 Characterization of Three Novel Enteropathies in Children With Unexplained Protracted Diarrhea Sergei Tatishchev, Martin G. Martin, Galen Cortina Background: Neonatal diarrhea may be due to congenital enteropathies; a subset of which is diagnosed by careful microscopic exam of small bowel mucosa. Three structural epithelial defects dominate this diagnostic category: microvillus inclusion disease (MVID), tufting enteropathy (TE) and enteroendocrine cell dysgenesis (ECD). These are distinguished from congenital enteropathies that are morphologically normal but are typically due to defective transport protein and digestive enzymes. These 3 dominant structural epithelial defects are diagnosed by routine H&E microscopy, immunohistochemistry and electron microscopy, but they have all been genetically characterized. We have found that the morphological approach can still identify subtle structural epithelial defects responsible for congenital diarrhea, and as such, distinguish them from morphologically normal mucosa. Aims: To illustrate that focused careful morphological exam of gastrointestinal mucosal biopsies with intact architecture ultimately reveals structural epithelial defect(s) responsible for more enteropathies than MVID, TE and ECD. Methods: Gastrointestinal mucosal biopsies from 3 pediatric patients (ages 2 - 40 months) with early-onset chronic unexplained diarrhea were studied using H&E, immunohistochemistry and electron microscopy. In addition, patients' DNA samples were partly characterized using Sanger sequencing and comparative genomic hybridization. Results: Three new enteropathies were identified in young children with intact mucosal architecture and preserved absorptive epithelial cells. All three patients showed loss of various secretory cells. Patient 1 (6 months old) born to a consanguineous couple shows loss of endocrine serotonin-secreting cells in gastric, duodenal and colonic biopsies. Comparative genome hybridization identified a defective prohormone convertase 1 gene. Patient 2 (2 months old) with Dandy-Walker malformation has absence of goblet, Paneth and endocrine cells in duodenal and rectal biopsies, absent CDX-2 expression and normal CDX-2 and HATH 1 genes by Sanger sequencing. Patient 3 (40 month old) with Zn-deficiency and repeated infections has loss of Paneth cells in duodenal biopsies; genetic studies are incomplete at this time. Conclusions: Herein we presented the morphologic description of three novel enteropathies based on epithelial defects. By using a combination of H&E and immunohistochemical studies we have identified patients with absence of 1) secretory epithelial cells, 2) enterochromaffin cells and 3) Paneth cells. This approach reinforces the principle that new congenital abnormalities with intact mucosal architecture can be identified through a careful morphologic examination.
Su1188 Serum Anti Sacromyces Cervecedes Antibody IgA (ASCA IgA) is a Novel Surrogate for Marker of Small Intestinal Bacterial Overgrowth (SIBO)-a Randomized Open Label Control Prospective Pilot Trial Patrick Basu, Thankam Nair, Mikram Jafri, Sakina Farhat, Sajith Foustin, Kavya Mittimani, Lynn P. Ang, Niraj James Shah Objectives:Small Intestinal bacterial overgrowth is a common clinical entity. Diagnostic aids are challenging without wide range of availability. ASCA IgA,IgG has been established for inflammatory Bowel Disease (IBD). This study evaluates the utility of ASCA IgA in SIBO. Methods; Hundred twenty (n=120) patients were recruited and divided into three groups: Group A (n=40) control, Group B (n=50) breath test positive,ASCA IgA positive, IgG negative and Group C (n= 30) Chron's disease in remission. All underwent pre and post Serum ASCA IgA and IgG ,AMCA,ALCA, ACCA, OMPC, Anti CHBR antibody, CRP, Breath testing and Colonoscopy with Ileal biopsy.SIBO positive subjects were given Xifaxan 550mg twice daily for 14 days. Exclusion: Celiac disease, Parasitic infestation, End stage liver, GI Tract malignancy, recent anti bacterial use. Results: In Group A, 3/40(7%) false positive ASCA IgA, rest of the antibodies were negative. Breath test positive 2/40 (5%). Post therapy 2/ 40(5%) ASCA IgA and breath test 2/40 (5%) remained positive. Group B post therapy 44/ 50(88%) Breath test Negative and 47/50 (94%) ASCA IgA negative. False positive breath test 6/50(12%) and ASCA IgA 3/50(6%). Group B rest of the Antibodies all negative pre and post except 2/50(4%)False positives AMCA and 1/50 '(2%) ALCA false positives. Group C Biopsy, ASCA IgA IgG positive ,breath test [ pre 3/30(10%) post 2/30(6%)] ASCA IgA ( false Negative ) 3/30( 10%) Summary:ASCA IgA is simple, Non Operator dependent, easily available in all the labrotaries,Inexpensive, relevant specific serum marker for SIBO. Larger study needs to validate. Table 1
Su1186 Mechano-Sensory Properties of Diabetic Intestine in Goto-Kakizaki Rats Jian Yang, Jingbo Zhao, Hans Gregersen Background: Up to 75% of diabetic patients have experience with gastrointestinal symptoms such as nausea, bloating, abdominal pain, diarrhea, constipation etc. but the pathogenesis is not well understood. Only few studies have addressed the sensory function where most studies were evaluated from central nerve system. However, the peripheral afferent nerves may likely be involved due to the complexity of gastrointestinal regulation and the enteric nervous system. In this study we investigated the afferent nerve trafficking from jejunum in a Go-Kakizaki (GK) type-2 diabetic rat model. Methods: Seven 32 weeks old male GK rats and seven age-matched normal Wistar rats were used. Afferent nerve activity was recorded under various mechanical stimulations in excised jejunal segments: 1) ramp test up to 60mmHg with two distension rates, 2) relaxation tests and 3) creep test with initial pressures of 20mmHg or 40mmHg lasting 300 seconds. The mechanical circumferential stress and strain were computed. The spike rate increase ratio (SRIR) was calculated for evaluation of nerve activity during the mechanical stimulation. The association between SRIR and muscle layer thickness were also analyzed. Results: At the termination of the experiment, the glucose levels were elevated in GK rats by 41%. Intestinal circumferential muscle layer thickness in diabetic GK rats was significantly thicker than that of normal controls. The stress-strain relationships showed no difference between groups. Elevated sensitivity to mechanical stimuli was found both for the SRIR-stress and SRIR-strain relationships (Figure 1, P<0.05). In the stress relaxation test, stress relaxed less in the diabetic than in the normal group (44.4% vs 64.8% in 20mmHg relaxation, 62.4% vs 76% in 40 mmHg relaxation, P<0.05). However, the normalized spike rate as function of time did not differ between normal and GK rats (P>0.05). In the creep test, no significant difference was found for either normalized strain or normalized spike rate between two groups. The linear association between SRIR and the thickness of circumferential muscle layer was found (Figure 2). Conclusion: Altered viscoelastic properties and elevated mechano-sensitivity in the small
AGA Abstracts
Su1189 Identification of Cardinal Symptoms in Patients With Chronic Idiopathic Constipation (CIC) Alan Joslyn, Laura Barrow, Gary Jacob, Jean Paty Plecanatide, a guanylate cyclase C agonist, is currently under clinical development for the treatment of CICAs part of the clinical evaluation of plecanatide, we undertook development of an instrument to collect Patient Reported Outcomes (PRO) on a daily basis. The purpose was to collect efficacy data for symptom-based secondary efficacy endpoints in support of
S-446