- Email: [email protected]
T1123 Esomeprazole for the Treatment of Gastroesophageal Reflux Disease (GERD) in Infants
T1121
a 4-week period) were eligible. During a 2-week open-label phase, patients received esomeprazole once daily orally: infants weighing 3-5 kg received esomeprazole 2.5 mg; those weighing >5-7.5 kg received esomeprazole 5 mg; and those weighing >7.5-12 kg received esomeprazole 10 mg. Infants who improved on the physician global assessment (PGA) during the open-label phase were eligible to be randomized to receive placebo or esomeprazole for the subsequent 4 week treatment-withdrawal phase. The primary end point was time from randomization to discontinuation due to symptom worsening in the withdrawal phase, analyzed using the Cox proportional hazards model, adjusting for treatment. Results: Of the 98 patients entered into the study, 79 (80%) showed improvement in PGA following treatment with open-label esomeprazole and 82% (80/98) were randomized into the doubleblind treatment-withdrawal phase. During the 4 week treatment-withdrawal phase, more infants randomized to placebo prematurely discontinued from the study (41.5%) compared with those randomized to esomeprazole (25.6%). Although there were more discontinuations due to worsening of symptoms for patients who received placebo (20/41, 48.8%) compared with those who received esomeprazole (15/39, 38.5%), this difference did not reach statistical significance (Hazard ratio, 0.69 [95% CI, 0.35-1.35] in favor of esomeprazole; P=.28). Following open label treatment only, downward trends indicating symptomatic improvement were noted in vomiting, irritability, and feeding difficulty symptoms only. The most common adverse events reported during the double-blind phase were upper respiratory tract infection (12.5%), pyrexia (10.0%), cough (8.8%), nasopharyngitis (8.8%), and rhinitis (8.8%). Conclusion: Approximately 80% of infants with suspected GERD who were treated with esomeprazole had improvement within 2 weeks of starting therapy. The results indicate that esomeprazole is well tolerated in infants and could be of clinical benefit for some infants with GERD. Supported by AstraZeneca LP
AGA Abstracts
Altered Development of the Glucagon Like Peptide-2 Response in Infants with Gastroschisis Ing Shian Soon, Dana Boctor, Jens J. Holst, Laurie E. Wallace, Viona Lam, David L. Sigalet BACKGROUND: Gastroschisis is an increasingly frequent congenital anomaly; feeding intolerance is a major problem during the early postoperative period. Recent data has described the importance of GLP-2 in the normal regulation of gut absorptive function and intestinal adaptation. Hence, we sought to describe the maturational changes of GLP-2 in infants with gastroschisis. METHODS: With IRB approval, families of infants diagnosed with gastroschisis (Gsc) at a tertiary children's hospital were approached to participate in the study. As part of their regular blood drawn, GLP-2 levels were obtained prior to feed initiation and followed weekly thereafter. Controls were recruited from infants admitted for non-gastrointestinal disease. GLP-2 levels were expressed as serum concentration (pmol/L) and to control for variations in caloric stimulation, accurate nutrition intake was recorded and GLP-2 production expressed per kilocalorie of feed/kg (pmol/L●kcal●kg). RESULTS: Eighteen infants with simple gastroschisis and ten controls were enrolled over a 2.5 year period. The mean gestational age for gastroschisis was 36.1±0.9 weeks, and 39.9±0.5 weeks for controls. Average hospitalization for gastroschisis was 64±35days. Infants with gastroschisis had lower fasting GLP-2 levels compared to controls (15±6 vs 23±4 (GLP-2 in pmol/L) in the first week. Initial post-prandial GLP-2 levels were decreased in Gsc infants versus controls, (34±6 vs 77±37), and these increased throughout their hospitalization, to 96±51 in the last weeks of hospitalization, in parallel with their tolerance of enteral nutrients. Controlling for caloric intake, the sensitivity of the infants to produce GLP-2 was highest in the mid-portion of their hospital stay, and decreased over the final weeks of hospitalization (controls: 5.6±2.7 vs. Gsc in mid phase of hospital stay: 17.5±10.5, in final week: 9.0±4.6, pmol/L●kcal●kg) (all comparisons p<0.05, data: mean ±SD). CONCLUSIONS: Infants with Gsc have a low basal production of GLP-2, at a developmental phase when normal infants have high levels. In parallel with reduced tolerance of enteral feeds, stimulated GLP-2 levels are decreased, but the sensitivity for release is accentuated. Delayed development of intrinsic enteric regulatory pathways may contribute to delayed intestinal function in Gsc infants. Further study is required, but this suggests that feeding patterns for Gsc infants should be optimized to increase endogenous GLP-2 production, and that the use of exogenous GLP-2 in these patients may be useful.
T1124 Common Clinical Problems Facing Pediatric Gastroenterologists in Outpatient Clinics At Academic Centers Dinesh Pashankar, Aliye Uc, Shehzad Saeed, Lesley J. Smith, Jeannie S. Huang, William R. Treem, Mark A. Gilger Background : The common gastrointestinal problems in childhood are vomiting, diarrhea, abdominal pain and constipation. Previous studies have described prevalence of these symptoms in community and in primary care pediatric clinics, however, there are no data about clinical problems seen in pediatric gastroenterology outpatient clinics. Aim : To assess the frequency of various clinical problems seen in pediatric gastroenterology clinics in academic centers. Methods : Outpatient data were collected from the program information forms (PIFs) submitted by seven pediatric gastroenterology fellowship programs at the time of their Accreditation Council for Graduate Medical Education review (2005-2008). Nineteen specific gastrointestinal problems seen at each program's outpatient clinic over the preceding 12 months were abstracted from the PIFs and were compiled. These problems covered majority of outpatient visits and included abdominal pain, vomiting including gastroesophageal reflux (GER), constipation, diarrhea, failure to thrive (FTT) , inflammatory bowel disease (IBD), functional bowel disorders (FBD) , liver failure/transplant, jaundice, malabsorption, peptic ulcer disease, allergy and bleeding. The data were collected by program directors via medical record compilation of diagnostic ICD-9 codes of primary clinical problems. The data were inclusive of both new and return outpatient visits. Results: Seven academic centers from different parts of the United States presented data for 33,115 outpatient visits. Seven common problems and percentage of the total are shown in the table. Other clinical problems encountered were liver failure/transplant (2.1%), bleeding (2.1%), allergy (2%) , malabsorption (1.9%) and peptic ulcer disease (1.4%). Vomiting including GER, abdominal pain, and constipation were among the top four problems in all seven centers with the median frequency rates of 18% (range 13-32), 14.5% (range 11-28), and 16 % (range 7-29) respectively. There was a wide variation in frequency rates of other presenting problems, probably reflecting referral practice patterns and the center expertise. Conclusions: This survey describes common clinical problems seen in the pediatric gastroenterology clinics at academic centers and has implications on fellowship training. Despite differences in geographical locations, expertise of the center and referral patterns, vomiting, abdominal pain and constipation emerged as most common problems facing pediatric gastroenterologists in the clinics.
T1122 Anti-Smooth-Muscle and Anti-Nuclear Antibodies Do Not Correlate with Increasing Severity of Liver Inflammation and Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease Kyle Kusek, Wallace Crandall, Kathleen Nicol, Laura Mackner, Carol Potter Background: Despite its high prevalence, little is known about the natural history of pediatric nonalcoholic fatty liver disease (NAFLD). Children with NAFLD may be identified via incidental findings of elevated serum aminotransferases (ALT and AST), via imaging consistent with hepatic steatosis, or through targeted screening of patients at risk for metabolic syndrome. The biochemical evaluation of these patients often includes testing for inflammatory and autoimmune causes of liver disease, including autoantibodies such as anti-nuclear antibody (ANA) or anti-smooth muscle antibody (SMA). Subsequent liver biopsy in these patients often reveals steatosis, inflammation, even fibrosis, but not autoimmune liver disease, even when positive autoantibodies have been noted. Aim: To determine if ANA and/or SMA status correlate with histologic severity on liver biopsy in patients with biopsy-proven NAFLD and no other apparent cause of liver disease, after a thorough evaluation. Methods: This retrospective review examined patients 18 years and younger with biopsy-proven NAFLD, over a period from 1995 to 2008. Excluded were patients with other causes of liver disease (infectious hepatitis, autoimmune liver disease, alpha-1 antitrypsin deficiency, Wilson disease) or prior steroid therapy. Individual data gathered (within 3 months prior to biopsy) included ANA titer, SMA titer, body mass index (BMI), ALT, AST, platelets, and erythrocyte sedimentation rate (ESR). A single pathologist blinded to the laboratory results reviewed biopsy specimens on all patients and scored them for percent steatosis, lobular and portal inflammation, and fibrosis according to Brunt criteria. Correlation analyses were conducted using Pearson's and Spearman's tests. Results: 37 patients (25 male) met inclusion criteria. Average age was 13.7 years (range 8 to 18 years). ALT level correlated with degree of steatosis (correlation coefficient 0.33, p<0.05) but not with inflammation. No significant correlations between ANA or SMA status, ESR, AST, BMI, or AST/Platelet ratio and biopsy findings (steatosis, inflammation, and fibrosis) were found. Conclusions: Our findings point to the difficulty of assessing histologic liver disease using commonly used clinical serum biochemical markers in patients with NAFLD. Although we did find correlation between ALT and steatosis, none of the variables tested, including ANA and SMA status, were predictive of inflammation and fibrosis. While non-invasive markers of liver fibrosis are being sought, liver biopsy remains the standard for determining disease severity in pediatric NAFLD.
T1125 Association of Ectopic Pancreas (EP) and Esophageal Atresia/TracheoEsophageal Fistula (EA-TEF) in Children Brigitte Moreau, Dominique Levesque, Christophe Faure EA-TEF is a frequent malformation which occurs in about 1 in 3000 live birth. EA-TEF can be associated with other congenital malformations. The aim of this study is to determine the prevalence of EP in children with EA-TEF and if other malformations can be associated with EP. Our hypothesis is that there is an association between EA-TEF and the EP. All patients with EA-TEF have been prospectively followed since 2005 at the Hopital SainteJustine and 2006 at the Montreal Children hospital. We compared 91 patients with EATEF who underwent a gastroscopy during that period to 182 control patients without EATEF who underwent a gastroscopy for an other indication. The control patients were arbitrary chosen from the archives of the gastroscopy procedures from the 2 pediatric gastroenterology divisions. The presence or not of EP and its localisation were noted for all patients and controls. For the patients with EA-TEF the following informations were also collected: sex, gestational age, type of EA-TEF and other malformations. 17 of the 91 patients with EATEF (18.7%) had an EP reported as a mass with central umbilication measuring about 2 mm to 4 cm compared to 1 patient (0.5%) in the control group (OR:42 [7-249] p= <0,001). All the EP were localized in the stomach, 16 of them specifically in the antrum. 88% of the
T1123 Esomeprazole for the Treatment of Gastroesophageal Reflux Disease (GERD) in Infants Harland S. Winter, Thirumazhisai S. Gunasekaran, Vasundhara Tolia, Frederic Gottrand, Peter N. Barker, Marta Illueca Aim: Many infants have symptoms of GER/GERD, and the use of acid suppressive therapy is common. This study was conducted to determine the efficacy and tolerability of esomeprazole in infants with signs and symptoms of GERD. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study (D9614C00096; NCT00468559), infants aged 1-11 months, inclusive, with GERD that was endoscopically proven or suspected clinically based on symptoms (ie, vomiting/regurgitation, irritability, supraesophageal symptoms, feeding difficulties, gagging/choking ≥2×/week in
AGA Abstracts
A-504
a 4-week period) were eligible. During a 2-week open-label phase, patients received esomeprazole once daily orally: infants weighing 3-5 kg received esomeprazole 2.5 mg; those weighing >5-7.5 kg received esomeprazole 5 mg; and those weighing >7.5-12 kg received esomeprazole 10 mg. Infants who improved on the physician global assessment (PGA) during the open-label phase were eligible to be randomized to receive placebo or esomeprazole for the subsequent 4 week treatment-withdrawal phase. The primary end point was time from randomization to discontinuation due to symptom worsening in the withdrawal phase, analyzed using the Cox proportional hazards model, adjusting for treatment. Results: Of the 98 patients entered into the study, 79 (80%) showed improvement in PGA following treatment with open-label esomeprazole and 82% (80/98) were randomized into the doubleblind treatment-withdrawal phase. During the 4 week treatment-withdrawal phase, more infants randomized to placebo prematurely discontinued from the study (41.5%) compared with those randomized to esomeprazole (25.6%). Although there were more discontinuations due to worsening of symptoms for patients who received placebo (20/41, 48.8%) compared with those who received esomeprazole (15/39, 38.5%), this difference did not reach statistical significance (Hazard ratio, 0.69 [95% CI, 0.35-1.35] in favor of esomeprazole; P=.28). Following open label treatment only, downward trends indicating symptomatic improvement were noted in vomiting, irritability, and feeding difficulty symptoms only. The most common adverse events reported during the double-blind phase were upper respiratory tract infection (12.5%), pyrexia (10.0%), cough (8.8%), nasopharyngitis (8.8%), and rhinitis (8.8%). Conclusion: Approximately 80% of infants with suspected GERD who were treated with esomeprazole had improvement within 2 weeks of starting therapy. The results indicate that esomeprazole is well tolerated in infants and could be of clinical benefit for some infants with GERD. Supported by AstraZeneca LP
AGA Abstracts
Altered Development of the Glucagon Like Peptide-2 Response in Infants with Gastroschisis Ing Shian Soon, Dana Boctor, Jens J. Holst, Laurie E. Wallace, Viona Lam, David L. Sigalet BACKGROUND: Gastroschisis is an increasingly frequent congenital anomaly; feeding intolerance is a major problem during the early postoperative period. Recent data has described the importance of GLP-2 in the normal regulation of gut absorptive function and intestinal adaptation. Hence, we sought to describe the maturational changes of GLP-2 in infants with gastroschisis. METHODS: With IRB approval, families of infants diagnosed with gastroschisis (Gsc) at a tertiary children's hospital were approached to participate in the study. As part of their regular blood drawn, GLP-2 levels were obtained prior to feed initiation and followed weekly thereafter. Controls were recruited from infants admitted for non-gastrointestinal disease. GLP-2 levels were expressed as serum concentration (pmol/L) and to control for variations in caloric stimulation, accurate nutrition intake was recorded and GLP-2 production expressed per kilocalorie of feed/kg (pmol/L●kcal●kg). RESULTS: Eighteen infants with simple gastroschisis and ten controls were enrolled over a 2.5 year period. The mean gestational age for gastroschisis was 36.1±0.9 weeks, and 39.9±0.5 weeks for controls. Average hospitalization for gastroschisis was 64±35days. Infants with gastroschisis had lower fasting GLP-2 levels compared to controls (15±6 vs 23±4 (GLP-2 in pmol/L) in the first week. Initial post-prandial GLP-2 levels were decreased in Gsc infants versus controls, (34±6 vs 77±37), and these increased throughout their hospitalization, to 96±51 in the last weeks of hospitalization, in parallel with their tolerance of enteral nutrients. Controlling for caloric intake, the sensitivity of the infants to produce GLP-2 was highest in the mid-portion of their hospital stay, and decreased over the final weeks of hospitalization (controls: 5.6±2.7 vs. Gsc in mid phase of hospital stay: 17.5±10.5, in final week: 9.0±4.6, pmol/L●kcal●kg) (all comparisons p<0.05, data: mean ±SD). CONCLUSIONS: Infants with Gsc have a low basal production of GLP-2, at a developmental phase when normal infants have high levels. In parallel with reduced tolerance of enteral feeds, stimulated GLP-2 levels are decreased, but the sensitivity for release is accentuated. Delayed development of intrinsic enteric regulatory pathways may contribute to delayed intestinal function in Gsc infants. Further study is required, but this suggests that feeding patterns for Gsc infants should be optimized to increase endogenous GLP-2 production, and that the use of exogenous GLP-2 in these patients may be useful.
T1124 Common Clinical Problems Facing Pediatric Gastroenterologists in Outpatient Clinics At Academic Centers Dinesh Pashankar, Aliye Uc, Shehzad Saeed, Lesley J. Smith, Jeannie S. Huang, William R. Treem, Mark A. Gilger Background : The common gastrointestinal problems in childhood are vomiting, diarrhea, abdominal pain and constipation. Previous studies have described prevalence of these symptoms in community and in primary care pediatric clinics, however, there are no data about clinical problems seen in pediatric gastroenterology outpatient clinics. Aim : To assess the frequency of various clinical problems seen in pediatric gastroenterology clinics in academic centers. Methods : Outpatient data were collected from the program information forms (PIFs) submitted by seven pediatric gastroenterology fellowship programs at the time of their Accreditation Council for Graduate Medical Education review (2005-2008). Nineteen specific gastrointestinal problems seen at each program's outpatient clinic over the preceding 12 months were abstracted from the PIFs and were compiled. These problems covered majority of outpatient visits and included abdominal pain, vomiting including gastroesophageal reflux (GER), constipation, diarrhea, failure to thrive (FTT) , inflammatory bowel disease (IBD), functional bowel disorders (FBD) , liver failure/transplant, jaundice, malabsorption, peptic ulcer disease, allergy and bleeding. The data were collected by program directors via medical record compilation of diagnostic ICD-9 codes of primary clinical problems. The data were inclusive of both new and return outpatient visits. Results: Seven academic centers from different parts of the United States presented data for 33,115 outpatient visits. Seven common problems and percentage of the total are shown in the table. Other clinical problems encountered were liver failure/transplant (2.1%), bleeding (2.1%), allergy (2%) , malabsorption (1.9%) and peptic ulcer disease (1.4%). Vomiting including GER, abdominal pain, and constipation were among the top four problems in all seven centers with the median frequency rates of 18% (range 13-32), 14.5% (range 11-28), and 16 % (range 7-29) respectively. There was a wide variation in frequency rates of other presenting problems, probably reflecting referral practice patterns and the center expertise. Conclusions: This survey describes common clinical problems seen in the pediatric gastroenterology clinics at academic centers and has implications on fellowship training. Despite differences in geographical locations, expertise of the center and referral patterns, vomiting, abdominal pain and constipation emerged as most common problems facing pediatric gastroenterologists in the clinics.
T1122 Anti-Smooth-Muscle and Anti-Nuclear Antibodies Do Not Correlate with Increasing Severity of Liver Inflammation and Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease Kyle Kusek, Wallace Crandall, Kathleen Nicol, Laura Mackner, Carol Potter Background: Despite its high prevalence, little is known about the natural history of pediatric nonalcoholic fatty liver disease (NAFLD). Children with NAFLD may be identified via incidental findings of elevated serum aminotransferases (ALT and AST), via imaging consistent with hepatic steatosis, or through targeted screening of patients at risk for metabolic syndrome. The biochemical evaluation of these patients often includes testing for inflammatory and autoimmune causes of liver disease, including autoantibodies such as anti-nuclear antibody (ANA) or anti-smooth muscle antibody (SMA). Subsequent liver biopsy in these patients often reveals steatosis, inflammation, even fibrosis, but not autoimmune liver disease, even when positive autoantibodies have been noted. Aim: To determine if ANA and/or SMA status correlate with histologic severity on liver biopsy in patients with biopsy-proven NAFLD and no other apparent cause of liver disease, after a thorough evaluation. Methods: This retrospective review examined patients 18 years and younger with biopsy-proven NAFLD, over a period from 1995 to 2008. Excluded were patients with other causes of liver disease (infectious hepatitis, autoimmune liver disease, alpha-1 antitrypsin deficiency, Wilson disease) or prior steroid therapy. Individual data gathered (within 3 months prior to biopsy) included ANA titer, SMA titer, body mass index (BMI), ALT, AST, platelets, and erythrocyte sedimentation rate (ESR). A single pathologist blinded to the laboratory results reviewed biopsy specimens on all patients and scored them for percent steatosis, lobular and portal inflammation, and fibrosis according to Brunt criteria. Correlation analyses were conducted using Pearson's and Spearman's tests. Results: 37 patients (25 male) met inclusion criteria. Average age was 13.7 years (range 8 to 18 years). ALT level correlated with degree of steatosis (correlation coefficient 0.33, p<0.05) but not with inflammation. No significant correlations between ANA or SMA status, ESR, AST, BMI, or AST/Platelet ratio and biopsy findings (steatosis, inflammation, and fibrosis) were found. Conclusions: Our findings point to the difficulty of assessing histologic liver disease using commonly used clinical serum biochemical markers in patients with NAFLD. Although we did find correlation between ALT and steatosis, none of the variables tested, including ANA and SMA status, were predictive of inflammation and fibrosis. While non-invasive markers of liver fibrosis are being sought, liver biopsy remains the standard for determining disease severity in pediatric NAFLD.
T1125 Association of Ectopic Pancreas (EP) and Esophageal Atresia/TracheoEsophageal Fistula (EA-TEF) in Children Brigitte Moreau, Dominique Levesque, Christophe Faure EA-TEF is a frequent malformation which occurs in about 1 in 3000 live birth. EA-TEF can be associated with other congenital malformations. The aim of this study is to determine the prevalence of EP in children with EA-TEF and if other malformations can be associated with EP. Our hypothesis is that there is an association between EA-TEF and the EP. All patients with EA-TEF have been prospectively followed since 2005 at the Hopital SainteJustine and 2006 at the Montreal Children hospital. We compared 91 patients with EATEF who underwent a gastroscopy during that period to 182 control patients without EATEF who underwent a gastroscopy for an other indication. The control patients were arbitrary chosen from the archives of the gastroscopy procedures from the 2 pediatric gastroenterology divisions. The presence or not of EP and its localisation were noted for all patients and controls. For the patients with EA-TEF the following informations were also collected: sex, gestational age, type of EA-TEF and other malformations. 17 of the 91 patients with EATEF (18.7%) had an EP reported as a mass with central umbilication measuring about 2 mm to 4 cm compared to 1 patient (0.5%) in the control group (OR:42 [7-249] p= <0,001). All the EP were localized in the stomach, 16 of them specifically in the antrum. 88% of the
T1123 Esomeprazole for the Treatment of Gastroesophageal Reflux Disease (GERD) in Infants Harland S. Winter, Thirumazhisai S. Gunasekaran, Vasundhara Tolia, Frederic Gottrand, Peter N. Barker, Marta Illueca Aim: Many infants have symptoms of GER/GERD, and the use of acid suppressive therapy is common. This study was conducted to determine the efficacy and tolerability of esomeprazole in infants with signs and symptoms of GERD. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study (D9614C00096; NCT00468559), infants aged 1-11 months, inclusive, with GERD that was endoscopically proven or suspected clinically based on symptoms (ie, vomiting/regurgitation, irritability, supraesophageal symptoms, feeding difficulties, gagging/choking ≥2×/week in
AGA Abstracts
A-504