North American Society for Pediatric Gastroenterology, Hepatology, And

Journal of Pediatric Gastroenterology and Nutrition 45:E1–E90 # 2007 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Abstracts North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Annual Meeting October 25–27, 2007 Salt Lake City, Utah

POSTER SESSION I colon. Furthermore, the patient’s colitis is indeterminate. THURSDAY, OCTOBER 25, 2007 Although no known patient with DC-associated IBD has ever been treated with infliximab, the patient has shown signifi- 5:00 PM – 7:00 PM cant improvement on this regimen. This case has significant implications for the role of the fecal stream in the pathogenesis of Intestine/Colon/IBD IBD and illustrates the systemic dimensions of a local disease. 1 2 INFLAMMATORY BOWEL DISEASE ASSOCIATED WITH A NEOVAGINA IN A PEDIATRIC PATIENT IS CBir1 A PREDICTOR OF PEDIATRIC Jonathan M. Gisser, Rebekah Slocum, Robert L. Parry, INFLAMMATORY BOWEL DISEASE? Jeffrey A. Morganstern1, Taaha Shakir2, Anupama Chawla1. Raymond W. Redline, Gisela G. Chelimsky, Reinaldo 1 Pediatrics, University Hospital Rainbow Pediatrics, Division of Gastroenterology, Stony Brook Garcia-Naveiro. 2 Babies and Children’s Hospital, Cleveland, OH. University Medical Center, Pediatrics, Stony Brook, NY.

Case: A 30-month-old caucasian girl presented with a one week Aim: Review charts of all pediatric patients at Stony Brook history of abdominal pain, fever, hematochezia and vaginal University Medical Center who underwent CBir1 (anti-flagellin) discharge. She had a congenital cloacal malformation that was testing to assess its diagnostic value for inflammatory bowel repaired in infancy with construction of a neovagina made from disease (IBD). a segment of her descending colon and a rectal pull-through. Methods: Forty patients were tested for the CBir1 marker since On admission, she was passing bloody stools from her it became available. Ages ranged from 6–19 and genders neorectum, and a bloody discharge from her partially prolapsed were 48% male, 52% female. The most common indications neovagina. She had hypoalbuminemia, leukocytosis and a were abdominal pain, irregular bowel habits, and hematochezia. markedly elevated inflammatory bowel disease (IBD) serolo- Sensitivity, specificity, and positive/negative predictive values gical marker (pANCA 192 EU/ml). Endoscopic examination were calculated. Diagnosis was based on interpretation of the revealed gastritis, duodenitis and colitis consistent with IBD. complete workup by a pediatric gastroenterologist. Her neovaginal inflammation, however, was more severe than Results: Twenty patients (50%) had positive CBir1 antibodies, her colonic disease. After a prolonged course, complicated above the cutoff of 21 EU/mL. Of this subgroup, 9 were diag- by Clostridium difficile neovaginitis and a poor response to nosed with IBD (PPV 45%). Seven of these 9 were also positive immunomodulator therapy with azathioprine, she improved for one of the more traditional markers (ASCA/OmpC/pANCA). on a regimen of subcutaneous methotrexate, intravenous inflix- Ten patients were positive for only CBir1, with no other IBD imab, and topical metronidazole to her neovagina. markers. In this group, only two patients were diagnosed with Discussion: This is an unusual case of probable diversion colitis IBD (PPV 20%). Eleven (48%) of the 23 patients without IBD (DC) associated with IBD. DC involves a segment of bowel were CBir1 positive. that has been diverted from the alimentary tract, such as a Conclusion: CBir1 is a poor predictor for IBD, compared to neovagina, and is treated by restoring bowel continuity. It is a ASCA. Combining the two markers improved overall sensi- relatively common occurrence among patients with sigmoid tivity and negative predictive value but specificity and positive neovaginas. However, there are only five reported cases of adult predictive value remained low. The above data are limited by patients with DC developing ulcerative colitis in the in-stream sample size and the duration offollow-up; therefore, evaluation of bowel. Ours is the youngest case of DC-associated IBD, and the a larger cohort of patients is warranted. While CBir1 may have only one involving the stomach and small bowel, in addition to the other uses, its utility as a diagnostic test for IBD in the pediatric patient appears to be limited due to a large number of false positive results. Until further studies are completed, we recom- Posters of Distinction. mend exercising caution in interpreting positive CBir1 results. E1 E2

Background: Serum antibodies are associated with Crohn’s CBir1 ASCA ASCA + CBir1 disease (CD), correlate with disease location, and predict dis- Sensitivity 53% 41% 76% ease phenotype. The aim of this study was to determine Speciﬁcity 52% 96% 52% relationships between serum antibodies and growth parameters PPV 45% 88% 54% in newly diagnosed pediatric CD. NPV 60% 69% 75% Methods: A retrospective review was conducted on children PPV of CBir1 in patients with no other positive markers is 20%. diagnosed with CD from 2003–6. All children who underwent IBD First Step (Prometheus Laboratories, Inc.; San Diego, CA) were included. Height (Ht), weight (Wt), and BMI prior to diagnosis and therapy were converted to Z-scores for age 3 and gender. Children with IBD Predicted, CD Predicted, GASTROINTESTINAL NOROVIRUS INFECTION and children with the presence of specific antibodies were ASSOCIATED WITH EXACERBATION OF compared to children with IBD Not Predicted using unpaired INFLAMMATORY BOWEL DISEASE t-tests. John N. Udall, Raheel R. Khan, Amana N. Nasir, Kathleen J. Results: 72 patients met inclusion criteria. Newly diagnosed Martin, April D. Lawson. Pediatrics, WVU Health Sciences CD patients with IBD Predicted and/or CD Predicted results had Center, Charleston Division, Charleston, WV. significantly decreased Ht and Wt Z-scores compared to newly diagnosed CD patients with IBD Not Predicted result. Patients Introduction: Norovirus is a common cause of acute gastro- with a positive ASCA IgA or IgG had significantly decreased enteritis in children and adults. The pathogenesis of Norovirus Wt and BMI Z-scores compared to those with IBD Not infection is poorly understood because the virus does not grow Predicted. Patients with a positive Anti-OmpC IgA had a well in cultured cells, and there is no commonly accepted small significantly decreased Ht Z-score compared to those with animal model to study the virus (Science 2003; 299:1575–8). IBD Not Predicted. Patients with a positive pANCA did not Infectious agents may be associated with exacerbations of inflam- differ from patients with IBD Not Predicted. matory bowel disease (IBD); however, there have been no reports Discussion: This study correlates growth parameters at diagnosis suggesting Norovirus may be associated with the disease. with serum antibodies in children with inflammatory bowel Methods: We performed a retrospective chart review of 8 IBD disease, and provides evidence that certain subsets of chil- patients with exacerbations since November 2006. We ident- dren diagnosed with CD are at greater risk of growth ified those with Norovirus documented by the presence of impairment. Norovirus antigen in stool samples and/or rectal swabs. Type of IBD, gender, age, presence or absence of diarrhea/hemato- Mean Anthropometric Z-scores in Patients With Newly chezia and the need for hospitalization was assessed. The charts Diagnosed Crohn’s Disease of six non-IBD patients seen in clinic who had Norovirus positive diarrhea were used as controls. IBD ﬁrst step n Mean height Mean weight Mean BMI Results: Of the IBD patients; 6 had UC, 1 had CD and 1 panel result z-score z-score z-score indeterminate colitis. All eight IBD patients presented with bloody diarrhea. Two patients also had other pathogens in the All Patients 72 0.33 0.54 0.41 stool including adenovirus and/or Clostridium difficile at the IBD Not Predicted 14 0.29 0.08 0.08 IBD Predicted 58 0.50 0.69 0.49 time they tested positive for Norovirus. All control group CD Predicted 51 0.61 0.99 0.82 patients experienced diarrhea, however no hematochezia was ASCA IgA + 37 0.40 0.77 0.69 noted. No control group patients required hospitalization. ASCA IgG + 24 0.32 0.97 0.90 Conclusion: We conclude that Norovirus may be associated OmpC IgA+ 21 0.80 0.88 0.28 with exacerbations of IBD. When Norovirus accompanies IBD pANCA + 18 0.19 0.26 0.27 it appears more likely to be associated with hematochezia and require hospitalization than when the infection occurs in the P < 0.05 compared to IBD Not Predicted. absence of IBD. Whether the virus initiates or contributes to the severity of an exacerbation or is a ‘‘bystander’’ during an exacerbation is not known. 5 AN EDUCATION PROGRAM FOR ADOLESCENTS Mean age Hospital WITH INFLAMMATORY BOWEL DISEASE Groups Sex (range) Diarrhea Hematochezia admission Lynelle M. Boamah1, Janet Bohren2, Raymond Baker1, Susan Moyer1. 1Cincinnati Children’s Hospital, Cincinnati, OH; IBD 5M/3F 14 y (10–17 y) 8 of 8 8 of 8 4 of 8 2University of Cincinnati. Non-IBD 5M/1F 13 y (10–18 y) 6 of 6 0 of 6 0 of 6 Background: 25% of patients with inflammatory bowel disease 4 (IBD) are diagnosed in childhood, particularly adolescence. Adolescents lack IBD-specific knowledge. There are no edu- SERUM ANTIBODIES AND GROWTH PARAMETERS cational programs for adolescent patients with IBD. AT DIAGNOSIS IN PEDIATRIC CROHN’S DISEASE Hypothesis: A well-designed education program for adoles- Anna Trauernicht, Steven Steiner. Indiana University School of cents with IBD using an interactive CD-ROM will significantly Medicine, Indianapolis. improve IBD-specific knowledge.

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Methods: IRB approval and informed consent/assent was Background: The diagnosis of Inflammatory Bowel Disease obtained. Assessment of baseline IBD knowledge was performed (IBD) is based typically on endoscopy and mucosal biopsy. on adolescents 13–17 years using the Crohn’s and Colitis Knowl- Compatible histopathology is crucial to distinguish IBD from edge Score (CCKNOW). Curriculum-based instruction was other chronic gastrointestinal conditions. This report describes designed using educational theory and principles. Modules on four children with chronic persistent, gastrointestinal symp- GI Tract Structure and Function, IBD Symptoms and Diagnosis, toms, who demonstrated histopathological progression from Complications, Medications, Nutrition and Social Functioning normal or indeterminate, to features typical of IBD on re- are taught. Videoclips of patient testimonials are included. evaluation for persistent symptoms and continued clinical Formative evaluation of the CD was performed using a teen suspicion of IBD. IBD focus group and critique by content and education experts. Methods: The retrospective chart review identified these 4 from Necessary modifications were made to produce a formal version a group of 104 children with IBD followed in our institution of the CD. Summative evaluation of the CD will be performed by from 2001 to present. In addition to the findings in the table measuring post-intervention gain in IBD knowledge on the below, charts were reviewed for laboratory and radiological CCKNOW. features. The biopsy was reviewed by a pathologist for accepted Results: The literature suggests that a 4-point increase in the acute and chronic features of IBD. Mononuclear infiltration mean CCKNOW score is sufficient to indicate that the alone was considered indeterminate. educational intervention is worthwhile. The mean CCKNOW Results: Summarized in table below. score of adolescents who participated in the pilot study was Conclusion: Atypical histopathology is previously described in 11/30 with a standard deviation of 4. A sample size of 29 new onset colitis in children. This series of children documents will have 90% power to detect an increase of 2.5 points in histopathological progression from normal or indeterminate the mean CCKNOW score using a 2-sided t-test with a of 0.05. features to classical IBD findings on follow up biopsies. The Conclusions: Educational modalities currently in use do not progession in histopathology occurred over a period of time in adequately teach the adolescent about IBD. The qualitative absence of change or progression in symptom pattern. Larger analysis has been completed on a rigorous interactive CD-ROM collaborative database analysis is necessary to identify charac- developed for teaching the adolescent patient about IBD. This teristic features, if any, of this subgroup of children with IBD. unique instructional program is based on learning theory and principles relevant to the adolescent learner. Summative evalu- 7 ation will show that knowledge significantly improves after completion of the CD-ROM. Testing of the program is in FUNCTIONAL GASTROINTESTINAL DISORDERS progress. AND VISCERAL HYPERSENSITIVITY IN CHILDREN AND ADOLESCENTS SUFFERING FROM CROHN’S DISEASE 6 Christophe Faure, Lyse Gigue`re. Ste Justine Hospital, Montreal, HISTOPATHOLOGICAL PROGRESSION TO IBD IN QC, Canada. CHILDREN WITH CHRONIC GASTROINTESTINAL SYMPTOMS Background: Symptoms of abdominal pain are reported by H. Shashidhar1, D. Whitehurst1, D. Flomenhoft1,E.Y.Lee2. children with active Crohn’s disease (CD). During remissions 1Pediatric Gastroenterology, 2Pathology, University of abdominal pain improves in most patients but some of them Kentucky Medical Center, Lexington. continue to experience pain. We hypothesized that these

Abstract 6 Table Age Interval IBD IBD No. (Yrs) Gender Initial biopsy Follow up biopsy (months) serology type Comment

1 11 M Normal except " rectal Active and chronic 5 Negative UC Rectal bleeding persisted to eosinophils pancolitis f/u endoscopy 2 10 M Normal except focal Acute and chronic 4 Not done CD Generalized pain and diarrhea. active inflammation inflammation; rectal Appendectomy 2 mo prior at IC valve granuloma to first endoscopy 3 10.5 M Normal Acute and chronic colonic 28 Negative CD Intermittent RLQ pain and inflammation; focal active watery diarrhea. Endoscopy ileum/duodenum at outside institution with normal biopsies prior to one reported here 4 11 F Normal Acute and chronic inflammation 31 ASCA positive CD Generalized abdominal pain; colonic, ileal and duodenal Trans-sphincteric rectal and vaginal fistula 4 mo after second endoscopy

Small bowel follow through normal in all except child #3 that showed nonﬁxed narrowing of ileal loops 2 m after ﬁrst endoscopy. subsequent SBFT at the time of second endoscopy normal. IC Valve, Ileocecal valve; UC, Ulcerative Colitis; CD, Crohn’s disease.

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E4 patients may suffer from protracted abdominal pain related metabolites. This required a mean decrease of 66% of the to functional gastrointestinal disorders (FGID) and visceral original 6-MP dose. It appears that in children, 6-TG levels hypersensitivity. fluctuate over time; thus, close monitoring of metabolites, CBC Objectives: To characterize the symptoms and to measure the and LFTs until levels stabilize is recommended. In children less rectal sensory threshold for pain (RSTP) by barostat in CD than 30 kg, an Allopurinol dose reduction to 50 mg/day is also children and adolescents with abdominal pain despite remission. necessary to avoid excessive shunting toward 6-TG which Patients and Methods: Six patients (median age 14.5 years; would increase risk for bone marrow suppression. range 8.5–17) with quiescent CD were studied by rectal barostat. At the same time, they completed validated questionnaires to assess FGID, anxiety and depression. They were compared to 9 10 control children also investigated in our laboratory. VALIDITY OF NOVEL IBD 7 SEROLOGY TESTING IN Results: Three patients fulfilled Rome II criteria for irritable A PEDIATRIC POPULATION WITH SUSPECTED IBD bowel syndrome, 2 for functional abdominal pain and 1 for Justine Dassa1, Devendra Amre1, Marla Dubinsky2, functional dyspepsia. RSTP was significantly lower in CD Colette Deslandres1, Ernest G. Seidman3. 1Gastroenterology, patients compared to the normal controls: median (range) Ste Justine Hospital, Montreal, QC, Canada; 2Pediatric IBD, 24 mmHg (16–33) vs. 40 mmHg (30–48) (P < 0.01). Cedars Sinai Medical Center, Los Angeles, CA; Rectal compliance was similar in both patients and controls 3Gastroenterology, Montreal Children’s Hospital. (9.7 mL/mmHg (3.1–11.2) vs. 8.7 mL/mmHg (4.2–14.7)). Five of the 6 patients had scores indicating an anxiety problem. Conclusion: A subset of children and adolescents with CD Background: Serological tests have potential to screen for IBD suffers from abdominal pain that is related to FGID associated and to discriminate between ulcerative or Crohn’s colitis (UC or with visceral hypersensitivity and anxiety. CD). A novel panel has been proposed with 7 components: ASCA IgA and IgG, anti-ompC, pANCA (i.ELISA ii.IFA iii.DNAse), and anti-CBir1, with titres analyzed by complex 8 pattern recognition software. Aim: To compare the diagnostic accuracy of IBD Serology 7 with the previous generation of IBD ALLOPURINOL IS EFFECTIVE IN OPTIMIZING serology (IBD First Step & Confirmatory System) in a pediatric THIOGUANINE (TG) METABOLITES IN PEDIATRIC population referred for suspected IBD. PATIENTS WITH INFLAMMATORY BOWEL DISEASE Patients and Methods: Serum was collected prospectively (IBD) OR AUTOIMMUNE HEPATITIS (AIH) (1997–2000) from 123 patients (<18 y) during diagnostic WHO PREFERENTIALLY METABOLIZE evaluation for suspected IBD. Medical records were reviewed 6-MERCATPTOPURINE (6-MP) TO (JD) blinded to serology results. Using standard clinical, radio- 6-METHYLMERCAPTOPURINE (6-MMP) logical, endoscopic and histological criteria, patients were Anca M. Safta, Kaylie Nguyen, William Berquist, Dorsey Bass, divided into 4 categories: CD, UC, indeterminate colitis (IC), James Lue, John Kerner. Pediatric Gastroenterology, Stanford and non-IBD controls. Final diagnoses were decided upon by University, Palo Alto, CA. adjudication by 2 IBD experts (CD, EGS) blinded to serology. All serology tests were performed at Prometheus Labs Background: A large number of patients with normal thiopur- (San Diego, CA). ine methyltransferase activity preferentially metabolize 6-MP Results: 65 of 123 children (53% prevalence) were diagnosed to produce 6-MMP instead of 6-TG metabolites. Allopurinol with IBD (58 CD, 4 UC, and 3 IC). IBD Serology 7 had a shunts the metabolism of 6-MP toward 6-TG. The safe use of significantly higher sensitivity vs the previous technology [86% Allopurinol for this purpose has not been demonstrated in the vs.72%, respectively; z = 2.69; P = 0.004]. The latter had a higher pediatric population. AIM: To describe the use of Allopurinol in specificity of 90% vs 76% for IBD Serology 7 (z = 2.92; pediatric patients who preferentially metabolize 6-MP toward P = 0.002). Positive and negative predictive values for IBD 6-MMP to deliberately shunt metabolism toward the active Serology 7 were 80% and 83%, respectively, compared to 6-TG metabolite. 89% and 74% for the previous technology (P = NS). IBD diag- Method: Ten patients ages 9–24 years with either IBD or AIH, nostic accuracy for the two tests was similar (80% for IBD whose metabolites demonstrated preferential metabolism Serology 7, 81% for previous technology) but was higher for towards 6-MMP were started on Allopurinol 100 mg daily while UC as compared to CD with IBD Serology 7 (80% for CD, 93% 6-MP was reduced by 50% of the original dose. 6-TG and 6-MMP for UC). metabolites, CBC and LFTs were obtained monthly until metab- Conclusions: This 1st prospective pediatric study results show olite levels stabilized along with adjustments in medication dose. that IBD Serology 7 is a sensitive test for detecting pediatric Results: With the addition of Allopurinol, 6-TG levels increased IBD and could help discriminate between UC and colonic CD. from a mean of 195.2 to 366.4 pmol/8 108 RBC while 6-MMP Larger prospective studies are needed to corroborate these decreased from a mean of 12,376.5 to less than 300 pmol/8 108 findings. RBC. The average dose of 6-MP dropped from a mean of 1.2 mg/kg/day without Allopurinol to 0.4 mg/kg/day with con- 10 current use of Allopurinol. Patients less than 30 kg required a reduction in Allopurinol dose by 50% as well. MEDICATION ADHERENCE IN PEDIATRIC IBD Conclusion: The concurrent use of Allopurinol with 6-MP in PATIENTS patients with preferential shunting to 6-MMP metabolites was Susan M. Jackson-Walker1, Jessica Block1, Devendra Mehta2, effective in shifting the metabolism toward the active 6-TG Gang Ye2, Joseph Truong2, Gabriela Ramirez2. 1A.I. duPont

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Hospital for Children, Wilmington, DE; 2Nemours Clinical Hypothesis: Elements of the Chronic Care Model (community Management Program, Orlando, FL. resources, health care organization, self-management support, delivery system design, decision support and clinical infor- Objective: The purpose of this study was to examine medi- mation systems) are positively associated with performance. cation adherence in pediatric IBD patients using an objective Methods: Using evidence and group consensus, the PIBDNet method. We also explored whether nonadherence is associated Trailblazer Improvement Collaborative developed recom- with disease symptomatology or level of clinical care. mended practices for Pediatric IBD care. Each of 7 centers Method: We examined a population of IBD patients (N = 254) performed a baseline chart audit on enrolled patients, recording seen in GI clinics from 5/06–6/06 (mean age = 14.5). We the number of recommended practices that were performed. selected those that were prescribed 5-ASA medications Centers also completed the Assessment of Chronic Illness Care (N = 181), and gathered pharmacy refill rates where that (ACIC) survey, a validated instrument to assess the 6 elements information was available (N = 151). Adherence rates were of the Chronic Care Model. calculated with a validated formula, and nonadherence was Results: A mean of 17 charts (range 13–20) were audited at defined as refilling less than 80% of prescribed medication each center. Overall, 62% (44% to 97%) of recommended (Kane et al, 2003). We gathered information from electronic practices were performed. The mean ACIC score was 4.0 out medical records regarding number of clinic visits, ER visits for of 11 (range 2.0 to 6.7), indicating basic chronic illness care. IBD, and hospitalizations for GI issues in the 3 months prior to Centers scoring higher had better performance of recommended the target visit. We also gathered information on disease practices (Spearman correlation r = 0.79, P = 0.04). symptomatology and whether the patient experienced pain or Conclusions: Centers vary in their performance of recom- interruption of daily activities. mended IBD practices. Clinical performance correlates with Results: Based on pharmacy refill rates, only 46% of patients chronic illness care delivery. Opportunities exist to improve were adherent with prescribed medication. There was no relation- the quality of care and systems of care delivery in pediatric ship between adherence and demographic variables, disease type IBD. (Crohn’s or Ulcerative Colitis) or disease symptomatology. How- ever, there was a significant relationship between adherence and 12 clinic visits, such that patients with more visits were more adherent than those with fewer visits (P < 0.01). IBD ACTIVITY AT INITIAL DIAGNOSIS: EFFECT OF Conclusion: Less than half of pediatric IBD patients are BODY MASS INDEX adherent with their 5-ASA medications. It appears that patients M. Greifer, S. Kugathasan, J. Hyams, N. LeLeiko, D. Mack, who are seen more frequently in GI clinics are more adherent. A. Griffiths, W. Crandall, A. Bousvaros, J. Evans, S. Moyer, While it is possible that frequent visits serve to remind and J. Rosh, A. Otley, M. Pfefferkorn, M. Oliva-Hemker, D. Keljo, maintain adherence, it may be that those more compliant also R. Carvalho, M. Kay, R. Baldassano, T. Lerer, J. Markowitz. attend clinic more consistently. However, this study points out Pediatric IBD Collaborative Research Group, Hartford, CT. that we have limited means of identifying nonadherence. In the future, it will be important to follow patients longitudinally in Background: We have previously demonstrated that at presen- order to determine whether adherence changes over time, based tation, 9% of children with Crohn’s disease (CD) and 20% of on disease course, and whether adherence can be improved with children with ulcerative colitis (UC) have high body mass index targeted intervention. (BMI). As adipose tissue is an important source of inflammatory cytokines, we hypothesized that children with high BMI have 11 more severeIBD activityat presentation than thosewithnormal or low BMI. THE QUALITY OF CARE IN PEDIATRIC Methods: Data were obtained from the Pediatric IBD Colla- INFLAMMATORY BOWEL DISEASE: DOES THE borative Research Group Registry, a prospective observational CHRONIC CARE MODEL WORK? database enrolling children with newly diagnosed IBD 1 2 2 3 3 M. Kappelman , P. Margolis , M. Moyer , S. Cohen , B. Gold , since 2002 from 18 centers in the US and Canada. Subjects’ 4 5 6 6 7 W. Crandall , A. Patel , D. Mehta , D. Milov , J. Grunow ,I. clinical and demographic information were obtained at time of 8 9 1 Leibowitz , R. Colletti . University of North Carolina, Chapel diagnosis. Comparisons for both CD and UC were made among 2 Hill, NC; Cincinnati Children’s Hospital Medical Center, 3 groups of subjects based on BMI Z-score (high: 1, average: 3 Cincinnati, OH; Children’s Hospital of Atlanta, Atlanta, 0.99 to 0.99, low: 1) at presentation. 4 GA; Columbus Children’s Hospital, Columbus, OH; Results: At presentation, 63 CD subjects (10.1%) had high BMI, 5 6 Children’s Medical Center of Dallas, Dallas, TX; Nemours 319 (51.4%) had average BMI and 239 (38.5%) low BMI. 7 Children’s Clinics, Orlando, FL; Oklahoma University Moderate/severe CD activity was seen in 55.9% of high 8 Medical Center, Oklahoma City; Inova Health Systems, BMI group, 63.2% of average BMI and 84.5% of low BMI. 9 Fairfax, VA; University of Vermont, Burlington. Low BMI subjects were more likely (P < 0.0001) to have moderate/severe CD activity than average or high BMI groups. Background: Differences in health care delivery systems can Gender, location of CD, and family IBD history were similar cause variation in the process and quality of care. in all groups. Among 240 UC subjects, 19.6% had high BMI, Aims: 1) To quantify inter-center variation in the performance 58.3% average BMI and 22.1% low BMI. As opposed to CD, UC of recommended practices in pediatric inflammatory bowel activity at presentation was similar in all 3 groups (range: 53.2– disease (IBD). 2) To identify factors of health care delivery 69.8% moderate/severe) as were gender, extent of UC, and family related to center performance. IBD history.

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Conclusions: About 10% of children with CD and 20% with Hospital, Academic Medical Center, Amsterdam, the UC are overweight or at risk for overweight at time of IBD Netherlands; 3University of Florida, Gainesville, FL. presentation. Those with high BMI Z-scores do not manifest more active disease. Further follow-up will be necessary to Background: Constipation is the most common functional determine whether the course of IBD is affected by BMI. gastrointestinal disorder in children with an estimated prevalence between 1% and 30% worldwide. Little is known about 13 health care use and costs due to childhood constipation. AIM: To evaluate the health care utilization and cost impact of CARD15 AND IL23R INFLUENCE IN SUSCEPTIBILITY childhood constipation in the US. OF CROHN’S DISEASE BUT NOT DISEASE Methods: The 2003–2004 Medical Expenditure Panel Survey, PHENOTYPE IN A BRAZILIAN POPULATION a nationally representative household survey was used to evalu- Ma´rcia L. Baptista1, Subra Kugathasan2, Heda Amarante4, ate patterns of health care use and costs related to childhood Vera Stepanian3, Geraldo Picheth1, Umesh Babasukumar2, constipation. The survey sample included 15,551 individuals Jose´ H. Cavalcante1. 1Internal Medicine, 4Gastroenterology, younger than 18 years. We identified anyone who either Parana Federal University, Curitiba, Brazil; 2Pediatrics reported constipation or received a prescription for laxatives Gastroenterology, Medical College of Wisconsin, Milwaulkee; in a given year. Individuals were counted only once over the 3Pediatrics Gastroenterology, Federal University of Sa˜o Paulo, 2 year period. Outcome measures were: 1) service utilization, 2) Sa˜o Paulo, Brazil. expenditures. Results: It was estimated that 1.1% (0.9 million) of US children Background and Aim: Although many genetic variants are were constipated in each year. No differences were found with identified in association with Crohn’s disease (CD), CARD15 respect to age, gender, race and socioeconomic status between and IL23R genes have been confirmed and replicated beyond constipated children and children without constipation. Consti- doubt in Caucasians of European ancestry. No studies have been pated children used more health services than children without reported in Brazil until now, and even far as we know, South constipation. The largest differences in utilization were for America. The aim of this study was to investigate CARD15 and outpatient visits (7.3 vs 3.0), inpatient admissions (0.15 vs IL23R variants in Brazilian population with CD and to perform 0.03) and ER visits (0.52 vs 0.16). Children with constipation genotype-phenotype analysis. had much higher health care expenditures ($3430 vs $1099/yr) Methods: Genotyping for CARD15 (R702W, G908R, which totaled to 3.0 billion dollars/yr. They also missed more 3020insC) and IL23R (rs1004819, rs7517847, rs11209026, days of school (mean 5.8 vs 2.5 days). rs1495965, rs10889677) was performed in 187 children and Conclusion: Childhood constipation has a significant impact on adults with CD and 255 healthy ethnically matched controls. health care use and cost for medical care services among US Clinical records were systematically reviewed, and detailed children. The estimated 3.0 billion US dollars cost per year is 3 phenotypic information was obtained. times higher than in children without constipation and probably Results: At least one CARD15 risk allele was present in 30.0% underestimates the real burden of childhood constipation since of the CD patients compared with 10.0% of controls. The CD it does not account for loss of quality of life, undiagnosed patient allelic frequencies were 9.62% for R702W, 1.87% for constipation, dietary changes, non traditional therapeutic G908R, and 3.47% for 3020 insC. Significant IL23R variants interventions, clothing/diapers expenses and over-the-counter associated with CD were found with the rs1004819, rs1495965, laxatives. and rs10889677. In contrast to other studies, no association was found between CARD15 variants and clinical data, and also 15 with the IL23R analysis. Demographic data showed a positive correlation between European/Brazilian subgroup with the COLONIC MOTILITY RESPONSE TO 3020insC and R702W risk alleles. ADMINISTRATION OF NORMAL SALINE INTO Conclusion: The risk alleles R702W and 3020insC for the THE PROXIMAL COLON CARD15 gene, and the rs1004819, rs1495965, and rs10889677 Roberto A. Gomez, Carlo Di Lorenzo, John Hayes, Hayat for the IL23R, confer susceptibility to CD in this Brazilian Mousa. Pediatric Gastroenterology, Columbus Children’s population study. A positive association with a combined IL23R Hospital, Columbus, OH. risk alleles and CD was observed for the markers rs1004819 and rs10889677. Background: Antegrade enemas with normal saline have been widely used to stimulate defecation in children with a cecostomy or an appendicostomy. Distension of the colon by the infused solution has been proposed as a mechanism to generate a colonic Motility/Functional Gastrointestinal Disorders motor response leading to aboral movement of colonic contents. Aim: To evaluate the colonic motor response to the adminis- 14 tration of normal saline into the proximal colon. HEALTH UTILIZATION AND COST IMPACT OF Methods: Pediatric patients undergoing colonic manometry CHILDHOOD CONSTIPATION IN THE UNITED received a saline infusion (10–20 ml/kg) over 10 minutes STATES through the central lumen of the colonic catheter into the most Olivia Liem1,2, Hayat Mousa1, Marc Benninga2, Kelly proximal segment reached by the catheter. We compared the Kelleher1, Jeffrey Harman3, Carlo Di Lorenzo1. 1Columbus presence of high amplitude propagated contractions (HAPC), Children’s Hospital, Columbus, OH; 2Emma Children’s motility index, frequency and propagation of other phasic

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E7 contractions in the 20 minutes before and after normal saline 2003 (11) and 2004 (24). 7 (16%) exposed patients and 3 (7%) infusion, meal ingestion and bisacodyl administration. The controls reported AP-FGIDs (P = 0.31). Children with later study was approved by the local IRB. AGE were not more likely to develop FGIDs than those with Results: 12 patients, mean age 8.7 (2–17) years received the earlier exposure. saline infusion(3 in the cecum, 7 in the hepatic flexure and 2 in the Conclusion: In children rotavirus associated AGEs do not result transverse colon). After saline infusion, number of contractions in AP-FGIDs. Larger, prospective studies should be performed P = 0.007), propagation (P = 0.014), frequency (P = 0.014), and to validate our findings. motility index (P = 0.004) were significantly higher compared to baseline. Mean amplitude (P = 0.197) and maximum amplitude 17 of contractions (P = 0.43) were not significantly different from baseline. Motility parameters after saline and after the meal did POSTINFECTIOUS FUNCTIONAL not differ (P = 0.32). All the measured motility variables signifi- GASTROINTESTINAL DISORDERS IN CHILDREN cantly increased after bisacodyl stimulation. Bisacodyl had a Miguel Saps1, L. Pensabene2, A. Staiano3, J. Weschler4, statistically greater effect on the motility index and on the X. T. Zheng5, C. Di Lorenzo6. 1Division of Gastroenterology, stimulation of HAPC than either saline infusion (P = 0.002) or Hepatology and Nutrition, 5Department of Microbiology, meal intake (P < 0.001). Children’s Memorial Hospital, Chicago, IL; 2Department of Conclusions: Infusion of normal saline into the proximal colon Pediatrics, University Magna Graecia, Catanzaro, Italy; is associated with an increase in motility and in the number 3Department of Pediatrics, University of Naples Federico II, of propagated colonic contractions possibly explaining its Naples, Italy; 4Department of Pediatrics, Indiana University, therapeutic effect when used as an antegrade enema. Infusion Indianapolis, IN; 6Columbus Children’s Hospital, Columbus, of normal saline at the volume and rate used in this study does OH. not reliably stimulate HAPC. Bisacodyl is a more powerful stimulant of HAPCs than either a meal or saline. Background: A higher prevalence of functional gastrointestinal disorders (FGIDs) following acute bacterial gastroenteritis 16 (ABGE) has been demonstrated in adults but not in children. Aim: To determine if patients exposed to ABGE have a higher VIRAL ACUTE GASTROENTERITIS: IS IT prevalence of FGIDs than healthy controls. Importance: First FOLLOWED BY ABDOMINAL PAIN? pediatric multicenter study designed to assess post-infectious Miguel Saps1, L. Pensabene2, A. Staiano3, D. Cupuro1,C. bacterial FGIDs. DiLorenzo3. 1Division of Pediatric Gastroenterology, Hepatology Methods: Multicenter cohort study. Inclusion criteria: Age and Nutrition, Children’s Memorial Hospital, Chicago, IL; 4–17, microbiologically proven ABGE. Exclusion criteria: 2Department of Pediatrics, University Magna Graecia, persistent diarrhea, immunological, allergic or inflammatory Catanzaro, Italy; 3Department of Pediatrics, University diseases. Sample: 44 patients each arm (unidirectional alpha of of Naples Federico II, Naples, Italy; 4Columbus Children’s 0.05, power of 0.80). Children consulting at two hospitals Hospital, Columbus, OH. (Chicago, IL, and Naples, Italy) with ABGE (2002–2004) were randomly contacted by phone >6 months after their positive Background: Long lasting abdominal pain-related functional stool sample. Each exposed child was matched with a control gastrointestinal disorders (AP-FGIDs) following bacterial of similar age and gender seen in the emergency room or acute gastroenteritis (AGE) have been described in adults outpatient site for trauma or well-child visit within 4 weeks and children. An adult study demonstrated AP-FGIDs following of the index case. Gastrointestinal symptoms and disability an outbreak of viral AGE. Viral AGEs in children are common. were evaluated with a validated questionnaire. Significance Thus, the demonstration of AP-FGIDs in children could con- among groups evaluated using chi square test. stitute a significant finding. Results: 88 subjects, 45 boys, mean age 8.4 years, (Caucasian Aims: To assess the development of AP-FGIDs in children 46, Hispanic 26, Black 6, other 4), were recruited. Positive following an AGE secondary to rotavirus. Importance: First cultures: Salmonella 24, Campylobacter 14, Shigella 6. 36% pediatric multicenter study designed to assess post-infectious exposed subjects and 11% controls complained of chronic viral AP-FGIDs. abdominal pain (AP) (P 0.01). 88% of children reporting Methods: Cohort study. Long-term follow-up. Inclusion AP had irritable bowel syndrome, 24% dyspepsia. 56% of criteria: Age 4–17 years, rotavirus proven AGE. Sample size: exposed subjects reported onset of AP following the ABGE, 44 exposed/44 controls (uni-directional alpha of 0.05, power of 38% preceded (rest unsure). 12% of exposed children complain- 0.80). Children consulting at two hospitals (Chicago, IL; ing of AP reported interference with school. Naples, Italy) for AGE (2002–2004) that tested positive for Conclusion: There is a significant increase in FGIDs following rotavirus were randomly selected and contacted by phone >2 ABGE in children. years after the episode. Each exposed child was matched with a control of same age and gender who visited the emergency room 18 or outpatient site for acute trauma or well-child visit within 4 weeks of the index case. Gastrointestinal symptoms and BIOFEEDBACK FOR MEDICALLY REFRACTORY disability were evaluated with a validated questionnaire. CONSTIPATION AND ENCOPRESIS Results: 88 subjects, 46 boys, mean age 5.3 (3–17) years, Ruby Ng1, P. C. Nguyen1, Ed Rich2, Antonio Quiros1. (Caucasian 83%, Hispanic 9%, Black 3%, other 5%), were 1Pediatric Gastroenterology, California Pacific Medical Center, recruited. Contacted patients presented with AGE in 2002 (9), San Francisco; 2Kaiser Permanente, San Francisco.

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Aims: To evaluate if biofeedback using electromyography region) over last week. Children with acute sickness were (EMG) improves outcomes in children with constipation and excluded. Obesity was defined as body mass index more than or fecal incontinence unresponsive to at least 6 months of 95th percentile for age and gender. Obese children were standard medical therapy. recruited from obesity clinic and the control group from Methods: Retrospective review of patients referred for con- general pediatric clinics. stipation and or encopresis. Patients received 6 biofeedback Results: There was no difference in prevalence rates of abdomi- sessions with video sessions and EMG. Outcome measures: nal and epigastric pain between two groups (Table 1). In the Clinical endpoints were regularity of bowel movements, con- subgroups of obese younger children (3 to 10 years) and obese tinence, and use of medications. Definitions: Success: Daily boys, prevalence rates of abdominal pain were higher compared bowel movements with total fecal continence. Good response: to respective control groups (11.7% vs 2.7% and 11.3% vs 3%; Regular bowel movements and < 2 encopresis episodes per week. P < 0.05). Race did not influence prevalence rate of abdominal Improvement: Decreased episodes of encopresis per week. pain in between two groups. When stratified by age, gender, Failure: No change in baseline toileting. and race, prevalence of epigastric pain was not significantly Results: Of 77 patients, 59 were available for follow-up, 45 different in between two groups. (76%) male. Age: mean 7.7 years, median 6 years (range 3– Conclusions: In this cross-sectional study, there was no differ- 17 years). 46 patients had functional bowel dysfunction: ence in prevalence rates of abdominal pain and epigastric pain 31 encopresis, 15 withholding. Organic etiologies were in obese children and normal-weight children. However, obese Hirschsprung’s disease, imperforate anus, bowel resection, boys and younger (3–10 years) obese children were more likely neurofibroma, and meningomyelocele. Table 1 shows regularity to have abdominal pain compared to respective groups of and continence after biofeedback. All patients had improvement normal-weight children. in bowel function. 19 patients (32%) had success, 23 (39%) had References: good response, 17 (29%) had improvement. No patients failed. 1. Malaty et al. Acta Paediatr 2007;96:572–6. 14 patients (24%) had decreased medication use. 45 patients 2. Nelson et al. Arch Pediatr Adolesc Med 2000;154:150–4. (76%) required the same medical therapy. No patients required more therapy. Supported by GCRC Grant & TAP. Conclusion: In children failing to respond to medical therapy alone, biofeedback to teach normal defecation dynamics TABLE 1. improves symptoms and may decrease medication use. Further research is needed to better identify patients refrac- Obese N = 283 Control N = 153 P value tory to medical management who might benefit from early intervention. Mean age, y 12.1 10.3 <0.01 Males 47% 44% NS TABLE 1. Regularity and Continence After Biofeedback Mean BMI 33.7 19.1 <0.001 Abdominal pain 13.8% 8.5% NS Diagnosis N Success (%) Good response (%) Improvement (%) Epigastric pain 13.4% 8.5% NS

Encopresis 31 8 (26) 14 (45) 9 (29) NS, Not signiﬁcant. Withholding 15 8 (53) 4 (27) 3 (20) Other 13 3 (23) 6 (46) 4 (31) 20 All 59 19 (32) 23 (39) 17 (29) SITZMARKER STUDIES HELP SELECT PATIENTS Hirschsprung’s n = 6, imperforate anus n = 4, bowel resection n = 1, FOR COLON MANOMETRY EVALUATION neuroﬁbroma n = 1, meningomyelocele n = 1. Neelesh A. Tipnis, Colin D. Rudolph, Steven L. Werlin, Sood R. Manu. Pediatric Gastroenterology, Medical College of Wisconsin, Milwaukee. 19 Introduction: Most children with constipation have a func- PREVALENCE OF ABDOMINAL PAIN IN OBESE tional disorder and improve with medical therapy. 33% children CHILDREN with chronic constipation have slow oro-anal transit time Dinesh Pashankar, Zachary Corbin, Syed Shah, Sonia Caprio. (OTT). Colon neuromuscular abnormalities, assessed using Yale University, New Haven, CT. colon manometry (CM), have also been reported in children with chronic intractable constipation. To date, no pediatric Background: We have reported higher prevalence of consti- studies have compared the OTT with CM findings in children pation and gastroesophageal reflux symptoms in obese children with chronic constipation. compared to normal-weight children. A recent study suggested Aims: To compare OTT measured by radioopaque markers with obesity as a risk factor for childhood recurrent abdominal pain.1 CM findings. We aimed to assess prevalence of abdominal pain in obese Methods: Records of 13 children with chronic constipation children and to compare it to a control group of normal [8 females; median age 12y (5–18y); median symptoms 73 mo weight children. (6–176 mo)] who underwent OTT and colon motility Methods: In a prospective study, 283 obese children and studies were reviewed. OTT was assessed by determining the 153 normal-weight children (3–18 years) were interviewed distribution of markers on an abdominal x-ray obtained 3 and 5 using a standard questionnaire,2 consisting of symptoms of days postingestion of a capsule containing 24 single pattern epigastric pain and abdominal pain (not in the epigastric radioopaque markers. Normal OTTwas defined as retention of 8

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E9 or fewer markers in the left or rectosigmoid colon 5 days HAPC’s. Presence of gastrocolonic response tended to a postcapsule ingestion. CM study was performed using an significant association with success of bisacodyl treatment 8 channel system and included continuous recordings of fasting (OR = 5, 95% CI 0.9–27). Presence of HAPC‘swas baseline, stimulated (bisacodyl) and postprandial segments of 1 not significantly associated with success of treatment with hour each. Normal CM was defined by the presence of HAPCs bisacodyl (OR = 2.7, 95% CI 0.75–10.2). (colonic contraction amplitudes of at least 60 mmHg propagat- Conclusions: Although a small sample, we found that colonic ing in an aboral pattern over at least 30 cm bowel). Normal manometry is a helpful tool to predict the response to gastrocolonic (GC) response was defined as a >30% increase in bisacodyl in the treatment of intractable idiopathic consti- contractility between fasting and postprandial segments. pation in children. This findings support the hypothesis that Results: See Table 1. OTT marker studies were 100% sensitive the integrity of the enteric nervous system (presence of and 71% specific for CM abnormalities. gastrocolonic response) is important in the mechanism of Conclusions: Normal OTT studies may predict normal colon action of bisacodyl as we have previously reported for manometry. However, abnormal OTT studies may not predict tegaserod. Prospective studies are needed to determine the abnormalities in colonic manometry or GC response in children role of bisacodyl in the long-term treatment of intractable with chronic constipation. Therefore, patients with slow transit constipation in children. marker studies should be assessed by colon manometry to evaluate colon neuromuscular integrity. 22 TABLE 1. Manometry in Slow and Normal Transit CORRELATION OF GASTRIC EMPTYING Constipation AND ANTRAL MOTILITY Leonel Rodriguez1, Philip Stein2, Alejandro Flores2. Normal Normal 1Pediatrics, Massachusetts General Hospital, Boston; Oral-Anal Overall HAPC Normal 2Pediatrics, Floating Hospital for Children, Boston. Transit Colon Spontaneous Stimulated Propaga- GC Time Manometry HAPCs HAPCs tion Response Background: The correlation between antroduodenal manome- Slow (N = 8) 2 0 5 2 4 try (ADM) and gastric emptying time (GET) in children is not Normal 52 554 well understood. We present a series of patients with symptoms of (N = 5) gastroparesis that underwent a scintigraphy GET and an ADM. Methods: 60 children with symptoms of gastroparesis seen at 2 tertiary centers from 2005 to 2007 undergoing ADM within 21 3 months of last GETwere included; a subset of 40 with delayed gastric emptying was separately analyzed. We compared the COLON MANOMETRY AND LONG-TERM USE OF change between motility index (MI) at fasting and EES and BISACODYL FOR INTRACTABLE CONSTIPATION IN fasting and meal challenge and also this change with the gastric CHILDREN emptying, also the correlation between the diagnosis of those Leonel Rodriguez. Pediatrics, Massachusetts General Hospital, changes reported visually by two physicians with the GET. Boston. Pearson’s correlation was used for the correlations and paired samples t-test was used to assess the significance on the change Background: There is no significant information about the of MI. long-term use of bisacodyl for intractable constipation in Results: Mean MI at fasting was 5.6 (SD 0.77), post-EES was children. 6.2 (SD 0.75) and postprandial was 6 (SD 0.67). Mean gastric Methods: Retrospective record review of patients with intract- emptying at 60 minutes with solids was 21% (SD 11.6) with able idiopathic constipation (poor response to stools softeners 75% emptying <30%, emptying with liquids was 41% (SD 23). and laxatives), patients with a known cause for constipation There was no significant correlation between the change of MI were excluded. The concomitant use of a stool softener was not from fasting to postprandial and GET at 60 minutes, also no an exclusion criterion. Our protocol for the management of significant correlation between the change of MI from fasting to intractable constipation includes a colonic manometry before EES and GET, in the total group and also in the gastroparesis the long-term (>4 wk) use of daily doses of bisacodyl, subgroup. There was a significant difference between the MI at parameters evaluated were gastrocolonic response to a meal fasting and after a meal and EES challenge. Particular in this and bisacodyl induced HAPCs. Patients took bisacodyl group was the increased proportion (30%) of side effects 5–10 mg per day for a minimum of 4 weeks and response requiring the discontinuation of metoclopramide, only one was measured by the change in frequency and consistency of patient from 13 using EES responded successfully, 5 out of bowel movements as reported by the parents at follow 16 using domperidone improved and 4 out of 20 using tegaserod up visits. responded favorably. Results: Forty patients were included in the study. A total of Conclusions: There is no significant correlation between 16 (40%) patients reported improvement with bisacodyl. gastric emptying and antral motility in this group of patients, Of those responders, colonic manometry showed presence ADM showed a significant difference on MI before and after of gastrocolonic response (visual and increase in motility the meal and EES. Further studies are needed to assess index) in 14 (88%) and HAPC’s (partially and fully propa- the role of GET and ADM in children with symptoms of gated) in 10 (63%) patients. Of the 24 nonresponders, gastroparesis, specially evaluating the outcome on different 14 (58%) had gastrocolonic response and 9 (38%) had therapies.

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23 metry and determine if any correlation exists with manometric variables. CLINICAL COURSE OF GASTROPARESIS IN Methods: 123 patients were prospectively enrolled and com- CHILDREN pleted symptom questionnaires. Anorectal manometry was Leonel Rodriguez, Katayun Irani, Allan Goldstein. Pediatrics, performed per standard protocol. Massachusetts General Hospital, Boston. Results: Of the 123 patients enrolled in the study 57.7 % were Background: There is no information on the clinical course of male. Patient age ranged from 0.2 to 17.8 years, and the mean gastroparesis in children; we present the largest epidemiologi- age was 7.5 years. The average duration of constipation was cal study of gastroparesis in children. 4.84 years. The average number of stools per week was 3.6. Methods: Retrospective record review of patients with delayed Average time spent in the defecation process was 13.3 minutes. gastric emptying by nuclear medicine from 1999 to 2006. The incidence of hematochezia was 30%. Delayed passage of Protocol was IRB approved. meconium was reported in 45 of 99 patients (45.5%) Significant Results: 225 patients were included (53% female, mean age correlation was found between frequency of soiling and threshold 7 years), 22% 1yo, 23% 1–5yo, 25% 5–10yo, and 30% >10yo. for Recto-Anal Inhibitory Reflex (RAIR) (P = 0.029). The Most common presenting symptom was vomiting, then abdomi- volume of first urge was also positively correlated with frequency nal pain and nausea, 20% reported a viral illness preceding of soiling (P = 0.034). There was significant correlation of with- symptoms. Comorbidities: mitochondrial dysfunction (10%), holding behavior and the maximum volume tolerated (P = 0.020). constipation (7%), milk allergy (7%), prematurity (4%), The presence of blood was inversely correlated with the maxi- cerebral palsy (4%) and DM type I (3%). Studies: UGI 32% mum volume tolerated (P = 0.004). No correlation was found (28% GER and 16% delayed contrast emptying), 10% pH study between severity of complaints and the presence of paradoxical (60% abnormal), 27% EGD (57% normal), 5% AD manometry puborectalis contraction, and 90.5% of patients did have para- (80% abnormal). Change on diet in 10% with 66% improve- doxical puborectalis contraction. ment but no resolution, all with milk allergy improved Conclusions: Anorectal manometry continues to be a valuable with formula change. Medications: 66% PPI and 19% meto- tool in evaluating patients with this very common chronic clopramide as the first therapy, 70% of PPI users reported pediatric affliction. Based on our findings we recommend improvement but only 6% did not require further treatment increased sitting times for scheduled toileting, and additional and 1% required discontinuation due to side effects; metoclo- attention should be paid to patients with delayed passage of pramide used in 71% and 54% reported improvement with 14% meconium. resolution of symptoms and 9% reported side effects requiring dose reduction or discontinuation; EES in 18% of patients with 45% reporting improvement, 12% resolution and 6% reporting 25 irritability; tegaserod in 6% of patients with 60% improvement CHANGES IN THE CHARACTERISTICS OF and 25% resolution; domperidone in 17% of patients with 80% SWALLOWS DURING SLEEP ARE THE RESULT improvement and 40% resolution, 3% reported side effects. OF DIFFERENT STAGES OF SLEEP Surgical procedures: 9% had a gastrostomy for failure to Hayat Mousa, Roberto Gomez, Sujit Philipose, Frederick thrive and 3% jejunostomy with good results. Information on Woodley. Columbus Children’s Hospital, Columbus, OH. resolution was available on 59%, 40% reporting resolution of symptoms at 1.3 years (range 1m to 6y, 90% <2 years, viral Background: Gastroesophageal reflux during sleep is one of the illness and lack of comorbidity correlated with more rapid and possible etiologies for sleep disordered breathing. The effect of complete resolution). Follow up was from 1 month to 6 years. sleep stage on the characteristics of swallowing and ultimately Conclusions: Gastroparesis in children is a poorly understood clearance of GER is not well understood. condition; prospective studies are needed to evaluate the Hypothesis: 1. Frequency and velocity of swallows during causality of viral infections and other comorbidities and also sleep vary based on the stage of sleep. 2. Changes in esophageal response to therapy. pH during sleep are a function of the sleep stage too. Aims: 1. Calculate the frequency and velocity of swallows 24 during all stages of sleep. 2. Measure the acidity of esophageal luminal contents during different stages of sleep. THE CONSTIPATED CHILD: IS THERE A Methods: We performed dual esophageal impedance and sleep CORRELATION BETWEEN SYMPTOMS AND studies on patient referred to our sleep lab during 2005–2006 MANOMETRIC FINDINGS? for sleep disordered breathing. Lisa Feinberg, Lori Mahajan, Rita Steffen. Department of Results: Nineteen patients (11M/8F), age 0.5–17 years, median Pediatric Gastroenterology, Cleveland Clinic, Cleveland, OH. 3 years with median BMI 17 underwent the sleep dual studies. Number of swallows per hour varied significant across stages of Background: Constipation is an exceedingly common problem sleep (P = 0.0021). Estimated number of swallows/ hour in pediatric medicine. Anorectal manometry is often used in the decreased significantly during stages III (8/hr) in comparison evaluation of children with long standing or refractory consti- to stages I, II and awake (12/hr, 12/hr and 12/hr), respectively, but pation. There is limited research done looking to correlate was the same as the number in stages IVand REM (10/hr, 10/hr). symptom severity in children and findings on rectal motility, Stages IVand REM are in the middle and not different from any with only one relatively small prospective study. other stages. Swallow velocity was a significant function of sleep Purpose: The aim of our study was to evaluate symptoms in stage (P < 0.001). Velocity of swallowing was significantly faster chronically constipated children undergoing anorectal mano- during stage I (3.2 cm/sec) in comparison to stage II (2.8 cm/sec),

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E11 stage IV (2.8 sec/min) and REM (2.8 cm/sec). Nadir pH was also duPont Hospital for Children, Wilmington, DE; 2Nemours a function of sleep stage (P < 0.001). pH during stage III was Clinical Management Program, Orlando, FL. lower than those during all other stages. Nadir pH during REM was lower than its nadir during stage I (P = 0.013) and during Objective: The purpose of the current study was to examine wake (P = 0.01). Conclusions: 1. Frequency of swallowing is behavioral and cognitive functioning, specifically attention and decreased during sleep stage III, 2. Velocity of swallows is learning difficulties, in children with secondary encopresis. compromised during all stages other than stage. 3. Changes in Methods: The sample consisted of 63 children aged 5 to esophageal pH are the result of the effect of sleep stages on the 14 years (mean age = 8.7; 67% boys) who were otherwise medi- frequency and velocity of swallows cally healthy. At their GI clinic visit, children were administered the Wechsler Abbreviated Scale of Intelligence (WASI) and the 26 Wide Range Achievement Test (WRAT3). Parents and teachers completed the Conners’ Rating Scales, which assess behaviors SEROLOGIC PREDICTORS OF CHANGES IN related to Attention-Deficit/Hyperactivity Disorder. Attention DUODENAL BULB EOSINOPHIL DENSITY WITH difficulties were defined as having one rater endorse difficulties MONTELUKAST THERAPY on the Conners’ scales at least 1.5 standard deviations above the Nancy Neilan1, Craig Friesen1, Jennifer Schurman2, Debra 1 1 2 mean, with the other rater endorsing behaviors at least one SD Taylor . Gastroenterology, Developmental & Behavioral above the mean. Learning difficulties were defined by having a Sciences, Children’s Mercy Hospital, Kansas City, MO. standard score on subscales of the WRAT3 at least one SD lower than the full-scale IQ score on the WASI. Objective: Montelukast is a competitive antagonist of the Results: Prevalence rates of ADHD and learning disorders in cysteinyl leukotriene-1 receptor. We previously demonstrated children in the US have been reported at 6.5 and 6.9%, respect- efficacy with montelukast in the relief of pain associated with ively (CDC, 2006). In this sample, 10.9–12.7% of the children functional dyspepsia in patients exhibiting duodenal eosinophilia were found to have symptoms consistent with an ADHD diag- (>20 eosinophils/high power field.) The aim of this study was to nosis on the summary scales. In addition, 17.5% were found to identify serologic markers as predictors of histologic response in have a reading difficulty, 12.7% were found to have a spelling children undergoing montelukast therapy for dyspepsia. difficulty, and 28.6% were found to have an arithmetic difficulty. Methods: We prospectively studied 18 children (13 F, 5 M; age Conclusion: Overall, these data suggest that attention and learn- range 9–16 years, mean 13 years) with dyspepsia unresponsive ing difficulties aremore prevalentinchildrenwithencopresis than to acid-reduction therapy who were undergoing montelukast in the general population. Research suggests that a large percen- therapy for duodenal eosinophilia. Grasp biopsies and plasma tage of children with encopresis experience failure with standard samples were collected pre-treatment and on day 21 of therapy. medical treatment, and subsequently require a more intensive Routine histology was performed and eosinophils were behavioral treatment program. It is possible that attention and enumerated by a single observer in a blinded fashion including learning difficulties are factors that interfere with effective treat- blinding as to whether biopsies were pre- or post-treatment. ment. Future research should examine whether these are risk Histologic response was assessed by determining the factors for treatment failure, and whether these children require post-treatment to pre-treatment ratio of peak eosinophil additional behavioral interventions to improve toileting. densities. Plasma was screened for potential biomarkers using a commercially available 25-plex cytokine kit with the Luminex platform. Global pain relief was assessed on a five- 28 point Likert-type scale. EGD FINDINGS IN CHILDREN WITH DYSPEPSIA AND Results: Pre-treatment concentrations of TNF-a (r= 0.527, FAILED ACID BLOCKADE THERAPY P 0= 0.025), MCP-1 (r= 0.517, P=0.028), and IL-8 Cass Smith, Dorota Walkiewicz, Manu Sood, Steven Werlin. (r= 0.490, P = 0.039) were negatively correlated with the Medical College of Wisconsin, Milwaukee. post-/pre-treatment duodenal bulb peak eosinophil density. Consistent with previous findings, nine subjects had a complete or nearly complete clinical response, six were improved but not Introduction: Children with dyspepsia, who fail to respond to resolved, and three had no change on the global pain relief scale. empiric treatment including PPI, undergo investigative workup The study lacked sufficient power to evaluate relationships which can include EGD. The yield of EGD is variable and between cytokines and clinical response. abnormal findings have been reported in 5% to 40% of subjects. Conclusion: TNF-a, MCP-1, and IL-8 pre-treatment plasma The aim of this study was to evaluate macroscopic and micro- concentrations show promise as predictors of changes in scopic abnormalities of the esophageal, gastric and duodenal duodenal bulb eosinophil density with montelukast therapy. mucosa in children with dyspepsia who have failed empiric acid A larger sample population needs to be evaluated to further blockade therapy. assess their usefulness as a surrogate marker. Methods: We performed a chart review of 1467 children with dyspepsia between Jan. 2001 and Jan. 2004. Inclusion criteria 27 were age between 5–18 years and abdominal pain for 3 months that did not respond to acid blockade. Exclusion criteria BEHAVIORAL AND COGNITIVE FUNCTIONING IN included known bowel or systemic disease, weight loss, hema- CHILDREN WITH ENCOPRESIS tochezia or hematemesis. Susan M. Jackson-Walker1, Jessica Block1, Jerrianne Kuntz1, Results: Out of 1467 patients, 52 patients met inclusion Devendra Mehta2, Colleen Lukens1, Roger Harrison1. 1A.I. criteria. The mean SD age at presentation was 12 3 years

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(range 5–17 years). The mean SEM duration of abdominal 30 pain was 35 5 weeks. Associated symptoms included vomiting (30%), nausea (11.5%) and early satiety (1.9%). Mild A COMPARISON OF 4 LAXATIVES USED TO TREAT abnormalities in ESR and CBC were present in 3 patients. CHILDREN (CHN) WITH RETENTIVE CONSTIPATION Two patients (3.9%) had macroscopic abnormalities on EGD (RC) that included duodenal ulcer (1) and esophageal plaques (1). J. Croffie, M. Davis, G. Waltz, J. Fitzgerald, J. Molleston, S. Histological abnormalities were present in 9 (17%) patients, Gupta, M. Corkins, M. Pfefferkorn, S. Steiner, J. Lim, G. Rao. including esophagitis (4), gastritis (3) and duodenitis (2). Post- Indiana University, Indianapolis. EGD treatment included PPI in 25 patients, with 68% reporting improvement. Another 25 were treated with amitriptyline for Background: MiraLax (MIR), Mineral oil (MO), Milk of presumed visceral hyperalgesia, 44% reporting improvement. Magnesia (MOM) & Lactulose (LAC) are used to treat RC. Conclusion: The yield of EGD in patients with dyspepsia is There are no reports comparing these laxatives for effectiveness low, with only 3.9% showing macroscopic abnormalities. in treating RC in CHN. However, 17% of our patients had microscopic abnormalities, Aim: Compare outcomes of 4 laxatives in treating CHN with RC. underscoring the need for routine biopsy in these patients. Methods: A randomized single blinded study with 8 months of Although all of these patients did not respond to acid blockade follow-up (FU). RC was defined as retentive posturing associated therapy prior to EGD, over 68% responded after EGD, with a bowel frequency of <3/week with or without encopresis. suggesting a placebo effect in some of our patients. Treatment Resolution was defined as discontinuation of retentive behavior with amitriptyline for visceral hyperalgesia was successful in associated with bowel frequency of 3/week and absence of 50% of patients, highlighting the functional nature of abdomi- encopresis. All CHN with a fecal impaction at time of enrollment nal pain in this group. were disimpacted with enemas prior to randomization. Results: 106 CHN ages 1–15 yrs (80M) were enrolled. An intention to treat analysis was performed. Patients withdrawing 29 prior to completion of study due to resolution of symptoms were consideredtreatmentsuccess.PatientslosttoFUpriortosecondof DIAGNOSTIC VALUE OF COLONOSCOPY IN 4 clinic visits andnoncompliant patients were considered failures. EVALUATION OF FUNCTIONAL CONSTIPATION Patients completing 2 of 4 clinic visits prior to being lost to FU IN CHILDREN were considered success or failure based on clinical status at Jennifer L. McCullough, James F. Daniel, Craig A. Friesen, Jeri last visit. J. Thompson. Gastroenterology, Children’s Mercy Hospitals Conclusions: 1) MIR & MO appear to be equally effective and and Clinics, Kansas City, MO. are more effective than LAC and MOM. 2) There were no statistically significant differences in the acceptance of the 4 Background: Constipation is most often functional in children. laxatives by patients. The term ‘‘functional’’ constipation implies that there is no underlying disease causing the constipation; however, there are no well accepted criteria for what testing is needed to rule out NC TF LTFU- LTFU+ COM+ COM- Total organic disease. Colonoscopy is sometimes performed in these patients; however, the clinical utility of colonoscopy has not MIR 2 5 11 7 6 1 32 been evaluated. LAC 6 12 3 3 2 1 27 MO 5 2 5 6 1 1 20 Patients and Methods: We retrospectively evaluated the MOM 5 9 5 3 3 2 27 records of 133 children (ranging in age from 14 months old- TOTAL 18 28 24 19 12 5 106 17 years old) who underwent colonoscopy from January 2002- December 2006 for a chief complaint of constipation. The NC = Noncompliance; TF = Treatment failure; LTFU- = Lost to clinical history, endoscopic findings, and biopsy results follow-up not better; LTFU+ = Lost to follow-up better; COM+ = Com- pleted study better; COM- = Completed study not better. were reviewed. Results: Melanosis coli was found in 3% of patients (4/133), ages 6–14 years old. Excluding melanosis coli, the incidence of Comparison of Outcomes positive findings was 5.3% (7/133 patients). The following positive findings were found in one patient each: pinworms Treatment Acceptance visually with acute colitis on biopsy, a juvenile polyp, eosinophilic colitis on biopsy, chronic active colitis on rectal biopsy, MIR v MOM P = 0.011 MIR v MOM P = 0.047 mild to moderate ileitis and mild active colitis on rectosigmoid MIR v LAC P = 0.001 MIR v LAC P = 0.596 biopsy, mild active colitis on rectosigmoid biopsy, and mild MIR v MO P = 0.667 MIR v MO P = 0.483 chronic and eosinophilic inflammation on rectosigmoid biopsy. All patients who had inflammation on biopsy also had other symptoms including abdominal pain, alternating diarrhea, 31 weight loss, hematochezia, and/or vomiting. Conclusions: The incidence of positive and potentially clini- FUNCTIONAL ABDOMINAL PAIN: A RETROSPECTIVE cally significant endoscopic findings in patients with consti- REVIEW OF SEASONAL VARIABILITY pation is higher than expected, but still low. Colonoscopy has Suma Nandakumar1, Muhammad A. Altaf1,2, John E. Grunow1. minimal clinical yield in the evaluation of constipation in the 1Pediatrics, University of Oklahoma, Oklahoma City; 2Medical absence of other associated symptoms. College of Wisconsin, Milwaukee.

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Background and Aims: Functional abdominal pain (FAP) Methods: A retrospective review of all computerized charts of severe enough to interfere with activities is a common problem children 6 to 12th grade presenting to a school based health of healthy school-aged children with a prevalence of 10–20%. center open all year round at an urban Chicago school from The proposed pathophysiology of these pain symptoms includes January 2005 through January 2006. Age, gender, race and abnormal motility, visceral hypersensitivity, inflammation and health insurance status were established and correlated with AP. autonomic activity. Pain can frequently be precipitated by a Results: 435 students (206 females), mean age 13.71.6 years. stressful event. Since school is a stressor for many children we 91% of children had public aid or no insurance. Total consul- investigated the relationship between the time FAP started and tations: 1,689. Consultants by race for all causes were African- the month of the year. American (67%), Hispanic (19%), Caucasian (3%) and mixed Patients and Methods: A retrospective chart review was done and other (11%). AP consultations: 79 in 60 children (18% of all children ranging from 4–19 years of age seen in one females, 10% males). 60/435 children consulted for AP investigator’s (JEG) pediatric gastroenterology clinic between (14%). Children consulting for AP had a similar race composition July 1, 1995 and June 30, 2004. Patients were identified by that children consulting for all causes. There is a trend of higher ICD-9 codes for abdominal pain. Patients were excluded if prevalence of consultations for AP but not for all other causes in they had an organic cause for their abdominal pain, had the winter compared with summer months. incomplete medical records, or came to clinic only once. Conclusion: There is a high prevalence of consultations for AP Patients were divided into groups based on the month of onset in inner city school children. The data on seasonal variation for of their pain: Group I- August to October, Group II- November AP seems to agree with outpatient based studies. The presence to January, Group III - February to April, and Group IV- May of an on-site clinic may increase the number of consultations to July. for AP. Results: Of the 346 patients evaluated, month of onset was available for 209. Mean age was 11 years and 56% were female. Pain started in August to October (Group I) in 36% of children 33 compared with 15% in Group IV (P < 0.001). The average THE HETEROGENEOUS PRESENTATIONS OF number of patients starting with abdominal pain each day was FUNCTIONAL ABDOMINAL PAIN (FAP) DEFY 0.82 patients every day from August to October compared with ATTEMPTS AT SYMPTOM-BASED CLASSIFICATION only 0.34 patients each day for those whose pain started during John T. Boyle1,2, Suzanne Hammett2. 1Children’s Hospital of May through July (P < 0.001). Philadelphia, Philadelphia, PA; 2Children’s Hospital of Conclusion: Onset of FAP demonstrates a seasonal variability Alabama, Birmingham, AL. with a peak during the months surrounding the beginning of school. Background: Symptom-based pharmacological therapy is the current standard practice for management of functional bowel 32 disorders in children. The Rome III classification of functional abdominal pain was developed with the hope that focusing SEASONAL NURSE CONSULTATIONS FOR on the main complaints reported by children to their ABDOMINAL PAIN IN AN ADOLESCENT parents would assist in the development of targeted treatment POPULATION strategies. Robroy Mac Iver1, Cynthia Mears1, Carlo DiLorenzo2, Methods: Using the computerized medical record we retro- Miguel Saps1. 1Children’s Memorial Hospital, Chicago, IL; spectively used the Rome III criteria to classify 523 consecutive 2Columbus Childrens Hospital, Columbus, OH. new patients diagnosed with FAP at the Children’s Hospital of Alabama between 5/03–5/06. Diagnosis of FAP was made if Background: We have previously shown the existence of a duration of pain at referral exceeded 6 weeks, physical exam- seasonal pattern of abdominal pain (AP) complaints and ination was normal, and either there were no alarm signals from outpatient consultations in children. A community based study history or screening labs, or work-up of alarm signals revealed by our group in two Chicago public schools showed that despite no evidence of an inflammatory, anatomic, metabolic, or neo- a 38% overall prevalence of AP only 2% of children consulted a plastic process. physician for AP. These findings raised the concern that studies Results: See Table 1. Within each FAP category, comparable on seasonal patterns of consultation conducted at the doctor’s numbers of patients awake at night with pain, are worriers, miss office may not fairly represent the pattern of AP complaints in significant days of school, and have symptoms of GERD, altered the community. bowel pattern, nausea, episodic vomiting, or early satiety. Hypothesis: There is a seasonal variation of consultation for AP Conclusion: The Rome III categories of FAP are not in school-age children. homogeneous and are unlikely to affect a symptom-based

Abstract 32 Table. Distribution by Month of Patients Complaining of Abdominal Pain Month Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

Percent of Cases Due to Abdominal Pain 6.54 5.85 2.82 2.76 2.49 2.97 0 0 8.07 5.63 3.85 7.48 Statistically Signiﬁcant Increase "" "" "

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Abstract 33 TABLE 1. Rome III category Dyspepsia Irritable bowel Functional pain Functional pain syndrome

No. of patients 153 (29%) 117 (22%) 105 (20%) 148 (28%) Mean age (yrs) 10.5 9.6 8.4 10.2 Female/male 88/66 69/48 58/47 87/61 Pain >3 months/6–12 weeks 82%/18% 87%/13% 79%/21% 80%/20% One constipation criteria 42% XXXXXX 57% 58% Additional somatic symptoms 61% 52% XXXXXX 74% >5 days missed school 36% 28% XXXXXX 55% Awake from sleep with pain 35% 30% 29% 45% Patient’sa‘‘worrier’’ 37% 27% 28% 39% Symptoms of GERD 54% 37% 33% 44% Nausea 50% 40% 41% 55% Episodic vomiting 39% 32% 28% 39% Early satiety 21% 14% 17% 17%

Only 9 patients fulﬁlled diagnostic criteria for abdominal migraine. pharmacological therapeutic approach to the individual patient specific HRQoL questionnaire for constipation and fecal with FAP. incontinence. Conclusion: Identifying concerns resulting from constipation 34 and its treatment will help to better target resources and treatment strategies to alleviate disease burden for the children and DEVELOPING AN INSTRUMENT TO MEASURE their families. The initial results of this study provide an insight DISEASE-SPECIFIC QUALITY OF LIFE IN into some of these issues. CHILDREN WITH CONSTIPATION Astrida Kaugars2, Margo Kinservik1, Alan Silverman1, 1 1 Manu R. Sood . Medical College of Wisconsin, Milwaukee; 35 2Department of Psychology, Marquette University, Milwaukee. FUNCTIONAL ABDOMINAL PAIN: A Introduction: There are no disease-specific health-related qual- RETROSPECTIVE REVIEW OF TREATMENT EFFICACY ity of life (HRQoL) questionnaires for childhood constipation and 1 1,2 1 generic HRQoL questionnaire lack sensitivity for discerning Suma Nandakumar , Muhammad A. Altaf , John E. Grunow . 1Pediatrics, University of Oklahoma, Oklahoma City, OK; unique concerns. 2 Methods: In the first phase of this study we recruited 16 children Medical College of Wisconsin, Milwaukee, WI. (11 males), between 7–13 yrs of age with constipation. Eight children and 8 parents completed a semi-structured Background and Aims: Functional abdominal pain (FAP) is a interview, which were audiotaped and transcribed. A multi- common problem of school-age children. Since reassurance is disciplinary team representing psychology, nursing and gastro- often not successful additional treatment options have been enterology independently reviewed 4 interviews and identified sought. The aim of this study was to investigate the effective- themes and definitions for coding categories. Two research ness of two drug treatments. assistants coded each interview and discrepant coding was Patients and Methods: A retrospective chart review was done discussed to achieve consensus. The study was approved by of all children with abdominal pain seen in one investigator’s the IRB. (JEG) pediatric GI clinic between July 1, 1995 and June 30, Results: The mean (range) age of children was 9.8 yrs 2004. Patients were excluded for organic causes, incomplete (7.1–12.7 yrs). Fourteen patients had history of passing large medical records, or only one clinic visit. Patients were diameter stool and overflow incontinence. Palpable abdominal clinically divided into three treatment groups. Treatment assign- fecal mass was present in 7 and rectal fecal mass in 7 children. ment for Groups A and B was based on the location of pain. High The following coding categories were identified: duration epigastric pain was treated with acid reducing medications of illness, knowledge, interventions, symptoms, toileting (ARM) (Group B). Pain in all other areas was treated with skills, adjustment, child’s social, independent and school func- hyoscyamine or amitriptyline (H) (Group A). Patients in Group tioning and impact on family. The following broad topics C were treated with a combination of H and ARM. were identified by children as being important to them: being Results: A total of 346 patients were evaluated, 210 (A), 88 (B), constipated (71%), going to see the doctor (57%) and affect of and 48 (C), with a mean age of 11 years and 56% female. The the illness on school (57%). Parents selected the following consistency of assigning treatment based on pain location was topics as important to them: the child using the toilet (75%), highly significant (P < 0.0001). Considering all treatments, 67% having accidents (75%), going to see the doctor (63%) of patients showed symptom improvement by visit 2, 3–4 weeks and getting support and understanding from others (63%). after visit 1 (P = 0.016) based on the physician continuing the From these broad categories we will identified 30 specific same treatment at visit 2. The mean time to improvement was items which will be used to develop and validate a disease 31 (A), 38 (B) and 33 (C) days. There was no significant

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E15 association of gender with improvement but children in Group A Background: Tegaserod (Zelnorm) a selective 5HT4 receptor showed a treatment response based on age. Of children younger agonist was used until recently as a prokinetic. 5HT4 receptors than 10 years old 68% reported improvement whereas only 39% are found throughout the GI tract and help regulate peristalsis, of those older than 15 years improved (P = 0.022). intestinal secretion, smooth muscle tone, and visceral sensitivity. Conclusion: Treatment with H and/or ARM is effective in FDA approval was in 2002 for the treatment of constipation improving FAP, usually within one month of starting treatment. predominant IBS in women and then in 2004 for idiopathic Efficacy of treatment correlates closely with treatment choice chronic constipation in men and women 18–65 yrs old. In March based on the location of the pain and age of the patient. 2007, it was withdrawn from the market due to a statistically significant number of cardiovascular ischemic events in adult 36 patients. The side effects of Zelnorm in the pediatric population have not been previously studied although it is used in many METHANE PRODUCTION AND BACTERIAL pediatric GI practices. OVERGROWTH IN CHILDREN WITH ENCOPRESIS Purpose: To evaluate for general as well as cardiovascular and Alycia A. Leiby, Vani Gopalareddy, Susan Jackson-Walker, neurologic ischemic side effects in pediatric patients prescribed Jerrianne Kuntz, Karoly Horvath. Gastroenterology, Zelnorm. A.I. DuPont Hospital for Children, Wilmington, DE. Patients and Methods: An IRB approved retrospective chart review was performed on 234 patients aged 21 and under Background: Breath methane (METH), as a by-product of prescribed Zelnorm. 133 charts had sufficient information for anaerobic bacteria, has been shown to be elevated in children analysis. with encopresis. Transit time is decreased in this population, Results: Indications for therapy were IBS 59.4%, chronic con- serving as a risk factor for small intestinal bacterial overgrowth stipation 21.1%, GERD 6%, pseudo obstruction 10.5%, gastro- (SIBO). paresis 10.5%, SMA syndrome 0.75%. 75.2% were female. Age Aim: To evaluate the prevalence of METH production and range was 2–20 yrs (mean 14.4 yrs). Average duration of therapy SIBO in children with encopresis compared to children without was 146 (range 2–1095) days. Mostcommoncomplaints reported encopresis or constipation. during therapy were abdominal pain (54%), continued consti- Methods: Lactulose breath tests preformed with a standardized pation (31.6%), and nausea (23.3%). No patients had new onset preparation in encopretic children prior to treatment and con- neurologic deficits. 4 patients had cardiac symptoms; 2 of which trols without constipation or encopresis from January 2005 to had postural orthostatic tachycardia syndrome (POTS), 1 had April 2007 were reviewed. The Quintron breath analyzer was panic attacks with anxiety disorder, and 1 had sinus bradycardia. used and hydrogen, METH and carbon dioxide were measured. All patients with cardiac symptoms had normal EKGs and METH production was defined as >3 ppm, high basal METH as no neurologic or cardiac side effects resulted in medication 10 ppm at time 0, and SIBO as H2 20 ppm or CH4 10 ppm discontinuation. The most common reasons for discontinuation above baseline within 60 min. The small intestinal transit time were completion of course 24.2%, diarrhea 19.7%, and no effect was estimated as H2 20 ppm or CH4 10 ppm above baseline 19.7%. after 60 min in patients without SIBO. An x-ray fecal impaction Conclusions: Zelnorm has been prescribed in pediatric patients score (FIS) from 0–3 was used for the encopretics. for a variety of indications. No cardiovascular or neurologic Results: In the encopretic group (ENCO) there were 43 pts and ischemic events were identified in any of the 133 pediatrics 28 males. The average FIS was 1.9 0.62. The control group patients. Based on our data, Zelnorm appears to be safe for use (CONT) had 34 pts and 22 males. The average age of ENCO was in the pediatric population. 8.72 2 yrs and 10.82 4.71 yrs in CONT. The BMI percentile of ENCO was 79.23 23.85 compared with 53.17 30.99 38 (P < 0.001). 55.8% of ENCO vs. 17.6% of CONT produced METH (P < 0.01) and basal METH was elevated in 46.5% of TREATMENT IMPLICATIONS OF REPRODUCIBLE ENCO vs. 11.7% of CONT (P < 0.01). SIBO was found in 37% ABDOMINAL COMPLAINTS DURING TILT of ENCO and 17.6% of CONT (P < 0.1). Transit time was TABLE TESTING 1,2 1,2 1,2 113.68 min in ENCO vs. 94.74 min in CONT (P = NS). Shaista Safder , Thomas Chelimsky , Gisela Chelimsky . 1 2 Conclusion: Methane production and elevated basal methane Case Western Reserve University, Cleveland, OH; Pediatric levels are found in significantly more encopretics than controls. Gastroenterology, Autonomic Disorders and Adult Neurology, More research is needed to determine if this is a product of or a Rainbow Babies and Children’s Hospital-University Hospitals contributing factor in their constipation. SIBO is found frequently of Cleveland, Cleveland, OH. in encopretics compared to controls but did not reach statistical significance. Transit time is longer but not statistically different in Background: Functional abdominal pain (FAP) in children encopretics without SIBO compared to controls. may respond to treatment aimed at orthostatic intolerance when tilt table testing replicates the abdominal pain. 37 The purpose of our study was to compare children with FAP whose symptoms tilt table testing reproduced with those in ZELNORM SAFETY PROFILE IN whom it did not. PEDIATRIC PATIENTS Methods: All children with FAP in the pediatric autonomic Aileen F. Har, Barbara Kaplan, Lori Mahajan. Pediatrics, gastroenterology database were included in this IRB-approved Cleveland Clinic, Cleveland, OH. retrospective chart review. The analysis included tests of

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Abstract 38 Table. Results Mean Sx POTS ON Abnl Abnl Abnl Florinef General treatment Age duration TTT VR DB AXR effect response

Reproduce GI Sx on Tilt n = 32 12.2 yrs 30 31 mo 28 (88%) 1 2 1.3 4.2 0.7 4.25 0.8 GI Sx not reproduce on Tilt n = 44 13.5 yrs 51 46 mo 31 (70%) 7 5 1.2 3.4 1.7 3.73 1.3 P value 0.09 0.03 0.01 0.01 0.05 0.7 0.15 0.14

autonomic function: cardiac reflexes (Valsalva ratio [VR] and (all P<0.001). But 6% of the subjects reported to have deep breathing [DB] responses) and vasomotor and sudomotor constipation and 18% of the subjects admitted to having at responses (tilt table test [TTT] and axon reflex test [AXR]), as least one symptom of constipation. 6% of the subjects were still well as response to treatment. Response to general treatment taking at least one type of treatment and another 6% of the and to fludrocortisone was ranked from 1 to 5 with 1 ‘‘much subjects reported to have significant impairment in social, worse’’, 3 neutral, and 5 ‘‘much better’’. Statistical analysis educational or occupational functioning. Male sex was the utilized student’s t-test or chi square as appropriate. only factor that influenced the persistence of constipation at Results: Tilt table reproduced abdominal complaints in 32 of 10–15 years f/u. 76 children with a diagnosis of FAP (table). POTS was more Conclusion: CIC in childhood is a common condition that can often present in the group with symptom reproduction, persist even 10–15 years after initial presentation. About 6% where there was a trend for better treatment response, while of the subjects reported to have constipation and 18% of the cardiac autonomic reflexes were more frequently abnormal in subjects continued to have at least one symptom of consti- the other group. pation even 10–15 years after initial presentation. More Conclusion: Children with reproducible GI complaints on tilt importantly, 6% of the subjects reported to have significant testing had a shorter symptom duration, more often had POTS, impairment in social, educational or occupational functioning. had normal cardiac autonomic reflexes, and responded better to Given the current prevalence of this condition in children, treatment. This subgroup of patients may represent a more development of an effective long-term intervention plan is benign group with better prognosis. recommended.

40 39 CONCEPTUALIZATION AND TREATMENT OF LONG-TERM FOLLOW-UP OF CHILDREN FUNCTIONAL GASTROINTESTINAL DISORDERS WITH CHRONIC CONSTIPATION IN PEDIATRIC GASTROENTEROLOGY PRACTICE Kirinmai Gorla2, Rita Steffen1, Gerard Banez3. Jennifer V. Schurman1, Heather L. Hunter2,1, Craig Friesen3. 1Pediatric Gastroenterology, 3Pediatric Behavioral Medicine, 1Developmental & Behavioral Sciences, 3Gastroenterology, Cleveland Clinic, Cleveland, OH; 2Pediatrics, MetroHealth Children’s Mercy Hospital, Kansas City, MO; 2Clinical Child Medical Center, Cleveland. Psychology, University of Kansas, Lawrence.

Aims: 1. Determine the outcome of chronic idiopathic con- This study examined how children with functional gastroin- stipation (CIC), 10–15 years later. 2. Determine the social, testinal disorders (FGIDs) are viewed, assessed, and treated educational and occupational functioning in children with by pediatric gastroenterologists across the country, and how CIC. 3. Determine the factors influencing the outcome in child- perspectives have changed since initial release of the hood CIC. Rome criteria approximately 15 years ago. In 2006, 174 Methods: Retrospective chart review followed by a telephone NASPGHAN members participated in a national survey interview. A total of 560 charts with CPT code for idiopathic regarding clinical practice for pediatric FGIDs. Results were constipation, seen between 1985–95, were randomly chosen compared to information collected from 151 NASPGHAN and reviewed. 231 subjects met our inclusion/exclusion members via a similar survey in 1992. The number of children criteria. Data was collected, and a follow-up questionnaire evaluated yearly for chronic abdominal pain in 2006 was was sent 2 weeks prior to telephone contact. A total of more than double the 1992 estimates. Nearly all physicians 73 (31.6%) subjects have responded when contacted by surveyed in 2006 reported having heard of the Rome criteria telephone. and/or being knowledgeable about it, but less than half Results: Mean age at initial presentation and f/u data collection indicated using this classification system in practice. In the were 5.3 and 22.4 years, respectively. More than 70% of area of functional dyspepsia, the frequency of using specific subjects had abdominal pain, stool impaction, large/hard evaluation tests as part of the initial workup changed from stools, painful defecation and stool withholding at initial 1992 to 2006; some tests became more common (e.g., gastric presentation. But at 10–15 years f/u, abdominal pain, painful emptying study, abdominal ultrasound) and others decreased defecation, rectal blood loss and hard stools were rare in use (e.g., urine labs). While the frequency of endoscopy

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E17 remained stable, esophageal, gastric, and duodenal biopsies Medians and 25th-75th Percentiles of Balloon-evoked increased. At both time points, less than half of patients were Propagated Contractions considered to have had a ‘‘good’’ clinical response to treat- Triggering pressure Mean amplitude Peak amplitude ment. Analysis of qualitative data summarizing physicians’ (mmHg) (mmHg) (mmHg) perspectives on a variety of topics, including the causes of chronic abdominal pain, typical treatments used, and the HAPC 25 (10–50) 92 (83–94) 140 (110–150) benefits/drawbacks of using the Rome criteria in practice, LAPC 30 (20–40) 37 (20–75) 60 (48–93) is in progress. Study results expand on existing literature by evaluating current conceptualizations of chronic abdominal Nutrition/Nutrition Support pain in children, physician awareness and use of the Rome 42 criteria, and the extent to which standards of care have changed over time. Findings will be critical in identifying GASTROSTOMY PLACEMENT FAVORABLY ALTERS where disconnects exist between theory and practice THE NATURAL HISTORY OF GROWTH FAILURE and facilitating the integration of both perspectives in future AND UNDERNUTRITION IN RETT SYNDROME 1 1 1 work. Kathleen J. Motil , Matthew Morrissey , Erwin Caeg , Judy O. Barrish1, Daniel G. Glaze1,2. 1Pediatrics, 2Neurology, Baylor College of Medicine, Houston, TX. 41 Background: Growth failure and undernutrition complicate the DISTENSION OF COLON ASSOCIATED clinical course of girls with Rett syndrome (RTT). These abnorm- WITH INITIATION OF PROPAGATIVE alities are, in part, the consequence of oral motor dysfunction and CONTRACTIONS IN CHILDREN inadequate dietary intake. Olivia Liem2,1, Maartje van den Berg2,1, Hayat Mousa1, Objective: Todetermine if gastrostomy placement for nutritional Nader Youssef3, Marc Benninga2, Carlo Di Lorenzo1. therapy alters the natural history of growth failure and under- 1Columbus Children’s Hospital, Columbus, OH; 2Emma nutrition in RTT. Children’s Hospital, Amsterdam Medical Center, Amsterdam, Hypothesis: We hypothesized that aggressive nutritional therapy the Netherlands; 3Goryeb Children’s Hospital/Atlantic Health with gastrostomy feedings normalizes height-, weight-, and body System, Morristown, NJ. mass index (BMI) z-scores in RTT. Methods: Height and weight were measured in a cohort of girls Background: The presence of high amplitude propaga- (n = 84) with RTT pre- (age 6.1 3.9 y) and post- (age 11.7 ting contractions (HAPC) on colonic manometry has been 6.1 y) gastrostomy placement with or without fundoplication. identified as marker of colonic neuromuscular integrity. The BMI was calculated from height and weight measures. Birth physiologic mechanisms of HAPC initiation have yet to be length and weight were recorded from parental recall. Height determined. (length), weight, and BMI measures were converted to z-scores Hypothesis: Intraluminal balloon distension of the proximal based on the NCHS standards. Paired t-tests were used to detect colon will induce HAPC in children with normal colonic differences in the change in height and weight z-scores pre- and motility. post-gastrostomy placement. Methods: Children with defecation disorders undergoing Results: Birth length and weight z-scores were 0.2 1.1 and colonic manometry were offered study participation. Colonic 0.4 0.9, respectively. Differences in the change in height manometry was performed according to established protocol (n = 56) and weight (n = 69) z-scores between birth to pre-gastro- (fasting, postprandial, bisacodyl stimulation). A manometry stomy and pre- to post-gastrostomy were 1.31 2.06 (P < 0.001) catheter with 8 side-holes (10 cm apart) with a polyethylene and 2.38 3.18 (P < 0.001), respectively. BMI z-scores balloon situated between the proximal 2nd and 3rd side-holes (1.24 1.76, P < 0.001) increased post-gastrostomy. BMI z- was used. The catheter was placed in the most proximal scores post-gastrostomy were higher in the subset of RTT girls colonic segment that was possible to reach. 1 hr postpran- (n = 58) with fundoplication than in those (n = 26) without fun- dially, a stepwise pressure controlled distension of the bal- doplication (0.4 1.23 vs. 1.13 1.47, P < 0.05). loon was performed using barostat computer (10–50 mmHg). Conclusions: Aggressive nutritional therapy with gastrostomy Each distension lasted 1 min. Propagated contractions, feeding alters the natural history of growth failure and under- migrating over at least 3 recording sites, were divided in nutrition in RTT. Fundoplication supports the reversal of under- HAPC, amplitude >60 mmHg and low amplitude propagat- nutrition in RTT. Further improvement in the genetic growth ing contractions (LAPC), amplitude <60 mmHg. potential of individuals with RTT is yet to be determined. Results: 13 children (6 boys, median age 11 yrs) were Supported by the Blue Bird Circle and Rett Syndrome Associ- studied. The barostat balloon was in the following positions: ation of Illinois. 2 in ascending colon, 4 in transverse colon, 5 in splenic 43 flexure and 2 in descending colon. Propagative activity was elicited by balloon distention in 9/11 children who had a NUTRITIONAL AND GASTROINTESTINAL normal response to bisacodyl. With intraluminal distension, PROBLEMS FREQUENTLY COMPLICATE THE 3childrenshowedbothHAPCandLAPCwhile6showed CLINICAL COURSE OF GIRLS AND WOMEN WITH LAPC only. RETT SYNDROME Conclusion: Colonic distension is associated with initiation of Kathleen J. Motil1, Erwin Caeg1, Judy O. Barrish1,DanielG. both HAPC and LAPC in children with a normal motor Glaze1,2. 1Pediatrics, 2Neurology, Baylor College of Medicine, response to bisacodyl. Houston, TX.

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Introduction: Rett syndrome (RTT) is a neurodevelopmental variable: Nutrition status. Independent variables: protein- disorder caused by a mutation in the MECP2 gene. Although energy income, diagnosis, age-group. Anthropometry: Mid classified as a neurological disorder, parents often seek medical upper arm circumference (MUAC), triceps skin fold (TSF) attention for the nutritional and gastrointestinal problems of and arm areas. Reference pattern: Frishancho and Sann. Stat- their daughters with RTT. istics: ANOVA, Wilcoxon, Student t and Mann-Whitney U. Objective: To determine the frequency of common nutritional Results: Mean age 80.6 68.2 months, 48.6% girls. Mean stay and gastrointestinal problems in RTT based on parental reporting. at ICU was 6.1 6.4 days. Mean NPO period = 92.6 11.7h. Hypothesis: We hypothesized that nutritional and gastrointes- 24.7% received TPN and 57% TEN. During the first 4 days the tinal problems frequently complicate the clinical course of girls mean energy received was <100 kcal/day; by day 7 it was <200 and women with RTT. kcal. At any time of the ICU stay the energy and protein Methods: The International Rett Syndrome Association administered reached the minimum nutritional requirements. (IRSA) mailed a survey related to the nutritional and gastro- The frequency of cases with MUAC <2 SD increased from intestinal health of individuals with RTT to its family-based 27.1% on admission to 42.1% on day 9th. A significant TSF membership. IRSA distributed the survey 6 months later to decrease was observed along the stay, reaching more than 1SD families who attended the annual family conference and had not loss in 7 days (P = 0.011). This impairment was reflected in the responded to the mailing. Upon receipt of all responses, IRSA total arm area measurements (loss of 0.88 SD in a week, de-identified the surveys for frequency analysis of the nutri- P = 0.08) but not in arm muscle area (P = 0.225). tional and gastrointestinal problems in RTT. Conclusions: AM developed in a significant proportion of Results: A total of 983 surveys (59%) were returned. The age patients; energy and protein administered were below their distribution of the RTT cohort was 0-10 y, 31%; 11–19 y, 30%; needs. Arm anthropometrics was sensitive in identifying pro- 20-29 y, 28%; 30-39 y, 11%; >40 y, 2%. The frequency of gressive changes in arm composition and may become a useful common nutritional and gastrointestinal problems are shown in clinical tool in the longitudinal evaluation of ICU patients. the table below. Conclusion: Nutritional and gastrointestinal problems fre- 45 quently complicate the clinical course of girls and women with RTT. Physician awareness of these problems may help to improve THE RATE OF INSULIN RESISTANCE AND the quality of life of individuals affected with this disorder. METABOLIC SYNDROME IN OBESE Supported by IRSA and the Blue Bird Circle. CHILDREN FROM WEST VIRGINIA Noeet Elitsur1, Yulia Dementieva1, Mary Rewalt1, 1 1 Common Nutritional and Gastrointestinal Problems in RTT Yoram Elitsur . Pediatrics, Marshall University, Huntington, WV. Weight problems 45% Gastrointestinal dysmotility 95% Undernutrition 36% Oropharyngeal incoordination 63% Background: The State of West Virginia has the highest rate of Overnutrition 9% Gastroesophageal reﬂux 38% obese children in the US. Insulin resistance (IR) and metabolic Feeding problems 62% Delayed gastric emptying 14% syndrome (MS) have been associated with high risk of cardi- Poor chewing ability 55% Constipation 81% Swallow dysfunction 43% Biliary tract disorders 3% ovascular disease and type-2 diabetes in children. Gastrostomy feedings 28% Osteopenia 17% Aim: To investigate the prevalence of metabolic syndrome and Formula supplements 47% Fractures 31% insulin resistance in cohort of obese children from WV. Methods: Cohort of obese children (BMI >95th percentile) were retrospectively evaluated for the following serum analysis: 44 fasting glucose, insulin, insulin resistance (QUICKI equation), HA1C, lipid profile (cholesterol, triglyceride, and HDL), and ACUTE MALNUTRITION IN A PEDIATRIC liver enzymes (ALT, AST). A repeat examination was performed INTENSIVE CARE UNIT: DIAGNOSTIC VALUE OF in a subset of the cohort at 3 to 6 months f/u. General instructions ARM ANTHROPOMETRICS on how to lose weight was given to the patients. Metabolic 3,4 1 Alfredo Larrosa-Haro , Martin Vargas-Nieto ,Irma syndrome was defined as the presence of 3 of the following 2 1,3 Rodriguez-Rodriguez , Rocio Macias-Rosales ,MariaE. risk factors: obesity, hyperinsulinemia, dyslipidemia, and hyper- 3,1 1,3 Camara-Lopez , Karina Rodriguez-Anguiano , Marc tension. 1,3 1 2 Mesa-Magan˜a . Gastroenterology and Nutrition, Intensive Results: A total of 85 patients were recruited, of whom only 78 3 Care Unit, Medical Research Unit, UMAE Hospital de had a complete set of data. A total of 19 (24%) patients had a 4 Pediatria, Guadalajara, Mexico; Human Nutrition Institute, second set of data at f/u visit. The mean age, and M:F ratio were University of Guadalajara, Guadalajara, Mexico. 8 years and 1:1.36, respectively. Insulin resistance was noted in 53 (68%) children and MS in 30 (38%) children. Multiple Background: The normal feeding process is abruptly stopped regression analysis showed a positive association between IR in critically ill children. It is unlikely they receive appropriate and ALT (P = 0.045). MS was significantly associated with age nutrition to cover their needs; and it is likely they present acute (P = 0.01), cholesterol (P = 0.002), and TG (P = 0.0002). Of the malnutrition (AM). Our aim was to estimate the energy and 19 f/u children, 10 lost weight (mean: 16 lbs, median: 13 lbs), protein administered to children attended in a pediatric inten- and 9 gained weight (mean: 6.4, median: 6.5). A significant sive car unit (ICU) and to evaluate their nutritional outcome. improvement in IR and cholesterol values was noted in children Methods: Design: Cross-sectional. Period: December/2006- who lost weight (P < 0.022) while no improvement in IR value February/2007. Sampling: n = 70, consecutive cases. Dependent was noted in the children who gained weight.

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Conclusion: IR and MS are highly prevalent in obese children 6% in the 1970’s to now over 16%. During this time there have (68% and 38%, respectively). In our study, loss of weight been numerous environmental and lifestyle changes including improved hepatocellular damage but not MS. To prevent cardi- increased consumption of sugar. Disappearance data demon- ovascular associated diseases, early medical attention in obese strates that the level of sugars and caloric-sweeteners in children is needed. the American food supply increased 21% from 1970 to 1997. The source of sugars in the diet has shifted from primarily 46 sucrose (from cane sugar) to corn based sweeteners resulting in an increase in consumption of free-fructose. Fructose is CLINICAL AND SOCIODEMOGRAPHIC PREDICTORS uniquely lipogenic and is unregulated by insulin and ATP OF SECONDARY MALNUTRITION AND OBESITY IN sensing pathways. Small studies of dietary fructose show it A PEDIATRIC REFERRAL HOSPITAL elevates triglycerides and causes insulin resistance in healthy 1,3 3 Roc´ıo Mac´ıas-Rosales , Edgar M. Vasquez-Garibay , subjects. No population-based studies have assessed fructose 2,3 1 Alfredo Larrosa-Haro . Gastroenterology and Nutrition, consumption. UMAE Hospital de Pediatrı´a CMNO IMSS, Guadalajara, Methods: Data was obtained from NHANES III, a stratified, 2 Mexico; Medical Research Unit, UMAE Hospital de Pediatria; multistage, probability cluster sample representative of the U.S. 3 Human Nutrition Institute, Universidad of Guadalajara. civilian, non-institutionalized population. Adolescents were defined as age 12 through 18 years. Other age groups were: Background: Children attended at pediatric referral hospitals 20-29, 30-39, 40-49 and 50-59 years. A 24 hour dietary recall share different mechanisms of secondary malnutrition (SM); was used to determine respondent’s diet (n = 22,047). however, it is not clear if besides their clinical condition, socio- Results: Mean fructose consumption was highest in adolescents demographic factors are associated to the nutritional status. (12.2 0.2% energy from fructose) compared to all other age Objectives: To build prediction models of the nutrition status groups. 63.8 1.6% of adolescents consumed 10% of total with clinical and sociodemographic factors as independent energy from fructose. 45.6 1.2% of the fructose came from variables. sugar sweetened beverages. No gender differences were Methods: Design: Cross-sectional. Sampling: Aleatory sample observed. from all medical and surgical departments, sample size n = 641. Conclusions: During the period of this study, fructose Period: IV-IX 2005. Dependent variable: Nutrition status. Inde- consumption was high in adolescents and the largest source pendent variables: Clinical, demographic and socioeconomic. is sugar sweetened beverages. Further studies will be necessary Anthropometry: Height/age, weight/height, BMI. Reference to assess if fructose consumption is a significant health risk to pattern: CDC, WHO classification. Statistics: Logistc regression. adolescents. Results: Mean age 7.05 49 years, 242 (44.3%) were females. Height/age <-2SD 17%. Weight/age <2 SD 8.0%. BMI > 95th 48 percentile 12.2%. Predictors of growth retardation were age groups (infants vs. preschoolers OR = 2.6; infants vs. scholars DISCORDANCE IN PHYSICIAN AND PARENT OR = 4.1; infants vs. adolescents OR 2.1; adjusted ORs, all with PERCEPTION OF FORMULA INTOLERANCE significant CIs) and illness duration (OR 2.0, CI 1-3.4). Predictors Carol Lynn Berseth, John Marunycz, Susan H. Mitmesser. of low weight were hospitalization vs. outpatient attention Medical Affairs, Mead Johnson Nutritionals, Evansville, IN. (OR = 2.3, CI 1.3-4.3), attention by the Medical vs. Surgical Division (OR = 2.1, CI 1.1-4.3) and number of siblings (one Background: Whether infants fed a marketed formula contain- sibling of single mothers younger than 20 years, OR = 1.3, ing partially hydrolyzed 100% whey experience better feeding CI 0.53.2). Predictors of overweight were age groups (scholars tolerance has not been tested in any reported study. Little is vs. infants, OR 10.7, CI 3.1-36.2) and father scholar degree known about the causes for parental choice to discontinue use of (professional vs. elementary, OR 2.1, CI 1.0-4.4). The predictors a given formula. of obesity were age groups (adolescent vs. infant, OR 2.6, CI 1.0- Objective: To compare drop out due to formula intolerance, 6.3) and gender (boys vs. girls, OR 1.8, CI 1.0-3). differences in parent and physician opinion of intolerance, and Conclusions: Predictors of SM were mainly clinical and bio- infant temperament when fed an intact protein formula or a logical; contrasting with primary malnutrition, sociodemo- partially hydrolyzed formula graphic factor did not play a role in SM. Predictors of overweight Methods: In this multi-center, double-blind, randomized, and obesity were age groups, gender and father scholar degree. controlled, prospective trial healthy, term infants (n = 333) were assigned to receive formula A (n = 165, a full lactose, intact cow 47 milk protein 60:40 whey:casein formula, Enfamil LIPIL, Mead Johnson Nutritionals) or formula B (n = 168, a 70% lactose, FRUCTOSE CONSUMPTION AMONG ADOLESCENTS, partially hydrolyzed 100% whey protein formula, Good Start NHANES III Supreme, Nestle). Infants were evaluated 4 times throughout the 1,2 2 2 Miriam B. Vos , Heidi M. Blanck , Cathleen Gillespie , 60 day study period. Discontinuation of assigned formula, 2 1 Joel Kimmons . Pediatrics, Emory University, Atlanta, GA; reasons for discontinuation, and results from an Infant Charac- 2 Division of Nutrition and Physical Activity, Centers for teristic Questionnaire (ICQ) (a validated infant temperament tool Disease Control and Prevention, Atlanta. which measures fussiness/difficulty, unadaptability, dullness, and unpredictability) were evaluated. Background: There has been a rapid rise of obesity, particu- Results: The number of discontinuations was similar between larly in adolescents, for whom prevalence increased from just formulas (see Table). There was a lack of concurrence of

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E20 parents’ and physicians’ opinion of discontinuation due to 50 formula intolerance (48 parents vs. 37 physicians, P = 0.001). There were no differences in infant temperament at day 60 A LARGE CASES SERIES OF CHILDREN WITH between formula A & B as indicated by ICQ. Nor was ICQ INTESTINAL FAILURE (IF): OUTCOMES OF NUTRITIONAL REHABILITATION predictive of formula change due to intolerance. 2 3 2 Conclusion: No difference in formula tolerance was observed Margareta Benser , Barbara Drews , Annette Cole , Maria-Paula Carrillo2, Naveen Mittal1. 1UTSW Medical Center, between the two formulas. Parents were more likely than 2 3 physicians to declare formula intolerance as the reason for Dallas, TX; Nutrition, Gastroenterology, Children’s Medical discontinuation. Infant temperament was not predictive of Center, Dallas, TX. discontinuation due to formula intolerance. Background: IF in children has high morbidity and enteral Discontinuation of Study Formula According to Physician’s autonomy seems an elusive goal despite availability of different Opinion (No. of Infants) formula choices & feeding techniques. We report experience in a large case series of IF children seen in our Intestinal Reha- Discontinuation for Discontinuation Due to bilitation Program (IRP). Any Reason formula Intolerance Methods: Retrospective data analysis of 101 IF patients seen in our IRP since inception of the program in July 2004. Formula A 44 17 Results: Out of 101 cases evaluated in IRP, 84 cases underwent Formula B 42 20 nutritional counseling and had initial and 3 months follow- up data for comparison analysis. At presentation, 37 (44%) cases were receiving parenteral nutrition (PN). PN was the sole 49 source of nutrition in 19 (22%) cases. Both PN and enteral MOVING FROM TUBE TO ORAL FEEDING IN feedings provided the nutrition in 18 (21%) and rest (47, 57%) MEDICALLY FRAGILE NONVERBAL TODDLERS were receiving supplemental enteral feedings. Gastroenterost- Ann M. Davis1, Cathy Mangiaracina2, Trina Schulz3, omy feeding was the commonest mode of supplemental Paul Hyman1. 1Pediatrics, 2Developmental Disabilities Center, feeding. Formula was elemental in 21 (30%), semi-elemental 3Occupational Therapy, University of Kansas Medical Center, 20 (30%), soy based 1 (1.5%), and cow milk based in 8 (12%). Kansas City, MO. At the 3 months follow- up of rehabilitation 8 came off PN completely and 29 could be weaned off PN either by Infants with long neonatal intensive care hospitalizations may reduction in duration (23) or calories (6) of PN per day. A miss opportunities for learning to eat, or associate eating with large number of IF cases (21, 30%) showed improved enteral pain or discomfort. Although the causes for prolonged hospital- tolerance by changing the formula. Choice of correct formula izations may resolve, a tube feeding requirement may persist. for the patient was based on many factors such as residual There are several methods for teaching nonverbal toddlers to eat, anatomy of gastrointestinal tract, and history of formula but no optimal solution. Our goal is to describe an outpatient intolerance due to allergies or diarrhea. After rehabilitation, method based on pain rehabilitation. Our feeding team, consisting formula was elemental in 31, semi-elemental in 13 and cow of a GI physician, pediatric psychologist, occupational therapist, milk based in 12. Calories derived from enteral source and dietician hypothesized that some toddlers refuse to eat improved in all either by changing the formula or advancing because they have functional dyspepsia (upper abdominal dis- the concentration or volume of the formula fed at the initial comfort worsened by eating) secondary to early childhood presentation. experiences such as endotracheal intubation. After the team Conclusions: Our IRP program improved enteral tolerance in opined that each subject had achieved the skills and behaviors majority of IF thus reducing the dependence on PN. Change to necessary for successful eating, we treated 8 toddlers (mean age right formula for the patient in up to one third cases was needed 30 mo, range 16-48 mo, 4 male, with extreme low birth weight or to improve enteral autonomy. cyanotic congenital heart disease, all fed by gastrostomy tube) for dyspepsia for 8 to 10 weeks. Treatment for dyspepsia consisted of 51 amitriptyline 1 mg/kg/d, gabapentin 10 mg/kg TID, and continuous drip gastrojejunal tube feedings 20 h/d. At the next visit the CENTRAL VENOUS CATHETER (CVC) ASSOCIATED team provided support and guidance and added the appetite SYSTEMIC INFECTIONS IN PEDIATRIC HOME TPN stimulant megesterol 3 mg/k BID. After 5 d megesterol we PATIENTS WITH INTESTINAL FAILURE reduced tube feedings progressively. After 25 d of megesterol Khiet D. Ngo, Evelyn Law, Rebecca Estanque, Jennifer subjects were exclusively eating orally. We discontinued meges- Peltzner, George Yanni, Marquelle Klooster, Darla Shores, terol after 6 weeks. Six of 8 subjects moved from tube feeding to Manoj Shah. Pediatrics Gastroenterology, Loma Linda oral feeding. One discontinued treatment because of negative University School of Medicine, Loma Linda, CA. behavior changes ascribed to megesterol. One subject was unable to maintain weight after tube feedings were withdrawn. In Background: Prior to the development of TPN the diagnosis of summary, there was 75% success treating medically fragile Intestinal Failure (IF) was universally fatal. Home TPN using toddlers with food refusal in a 14 week outpatient pain treatment CVC can prolong the lives of children with IF indefinitely. CVC program. These data suggest that food refusal may be a pain associated infections are leading causes of morbidity and symptom in at least some nonverbal children. mortality in children with IF.

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Methods: Retrospective review. Inclusion criteria: 1) children according to BMI. Health knowledge and health control were <18 y/o with IF with >6 months follow-up. 2) Available not altered. complete medical and surgical records. Conclusion: Obese food consumers perceive themselves as less Results: 11 patients comprising 35 TPN patient-years were healthy, possess less control of behaviors pertaining to healthy identified. M:F was 4:7 with a mean age of 3.5 y (0.5–7.7y). lifestyle, and buy more impulsively than their non-obese Causes of IF included: NEC (3), gastroschisis (2), atresia (2), counterparts. Initiatives, at point of services such as super- perforation (1), volvulus (2), and autoimmune enteropathy (1). 10 markets, are necessary to address these counterproductive of 11 patients had SBS with an average remaining SB length of consumer habits to combat the obesity epidemic affecting adults 29 cm (15.3) at the time of initial surgery; only 1 patient had an and their offspring. intact ileocecal valve. There was an average of 5 hospitalizations per patient per year; over 50% of hospitalizations were related to Consumer Characteristics suspected bacteremia. 89 episodes of bacteremia/fungemia were identified within the 35 patient years. Of the 89 episodes, 79 grew Health Behavior Buying 2 gram positive and 37 grew gram negative bacteria, and 14 grew BMI (kg/m ) Status Control Impulsiveness Candida. Out of the 89 episodes of CVC related infections, 18.5 to 24.9 (n = 103) 5.70 1.04 (a) 59.6 9.1 (c) 27.3 8.4 (e) 69 were treated conservatively while 20 required CVC removal 25.0 to 29.9 (n = 68) 5.28 0.99 (a) 56.9 8.8 30.6 9.3 due to either overwhelming sepsis or the inability to eradicate the >30 (n = 47) 4.21 1.77 (b) 54.8 11.0 (d) 31.9 9.4 (f) offending organism which consisted of CONS (5), Candida (10), or 1 each of: Bacillus cereus, Brevibacterum, Enterococcus, P (a,b)<0.001; P (c,d)<0.05; P (e,f)<0.05. MRSA, and Streptococcus viridans. Conclusions: 1. Bacteremia is a common complication of home TPN infusion and indication for hospitalization. 2. The shorter 53 CVC lifespan in our population compared to previous reports REGIONAL INTESTINAL COLONIZATION may reflect a more severe disease process. 3. Most episodes of OF ORALLY ADMINISTERED LACTOBACILLUS bacteremia can be successfully treated while most candidemia REUTERI STRAINS IN PIGS require CVC removal. 4. Additional studies are needed to find Steven Kim1, Iyer Chandra2, Angela Major2, ways to reduce the numbers of CVC related infections, which James Versalovic2, Barbara Stoll3, Douglas Burrin3. 1Pediatric may include better training of home TPN techniques for care Gastroenterology, 2Pediatric Pathology, 3Pediatrics, providers. USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX. 52 Purpose: We quantified regional gastrointestinal (GI) tract FOOD CONSUMER CHARACTERISTICS: A ROLE colonization and persistence of human-derived Lactobacillus IN THE OBESITY EPIDEMIC? reuteri (L. reuteri) strains MM2-3 and MM4-1A and measured 1 2 3 Mark Fishbein , Greg Bennett , Siva Balasubramanian . the effects on intestinal growth and mucosal morphology in 1 Gastroenterology, Children’s Memorial Hospital, Chicago, weanling pigs. 2 IL; Pediatrics, Southern Illinois University School of Methods: Forty-five, 28 day-old pigs were assigned to 3 groups 3 Medicine, Springfield, IL; Marketing, Southern Illinois and given a daily oral treatment of either control, L. reuteri University, Carbondale. MM2-3 (5 109 cfu/day), or L. reuteri MM4-1A (5 109 cfu/ day). Pigs received treatment for 14 days, then discontinued and Introduction: Environmental factors, including increased followed for another 14 days. Half the pigs from each group were availability and consumption of non-nutritious food items, euthanized on day 14, the remaining pigs on day 28 to determine are believed to be a major contributor to the obesity epidemic. L. reuteri colonization. The supermarket, as a point of service for food consumers, Results: Based on fecal sampling and reuterin-specific cultur- represents a potential site of intervention to improve health. In ing L. reuteri strains MM2-3 and MM4-1A rapidly colonized this study, food consumer characteristics are compared among the gut. Colony counts increased from 106 to 108 cfu/g in both adult subjects according to their BMI to determine future groups within one day of treatment and peaked at 109 cfu/g after treatment strategies. 7 days treatment. Additional fecal analysis found that L. reuteri Methods: Pediatric caretakers escorting their children to a strains persisted in the gut for at least 4 days after withdrawal, university based ambulatory clinic were provided with a ques- but returned to control levels within 7 days. Reuterin-specific tionnaire containing information regarding their food purchas- cultures of gut contents after 14 days of treatment showed that ing characteristics and demographics. Categories included counts of both L. reuteri strains were significantly increased health knowledge (understanding consequences of consuming above control (log 1–2 cfu/g) throughout the small and large specific nutrients), health control (belief that health outcomes intestine. Interestingly, after 14 days of probiotic withdrawal, are controllable), health status (excellence of current health), the colony counts of both L. reuteri strains were persistently behavior control (control of behaviors promoting good health), higher in the proximal small intestine. Neither L. reuteri strains and buying impulsiveness (measures impulsiveness of pur- resulted in any remarkable changes in total body weight gain, chase). One way ANOVA and Bonferroni post hoc analysis histomorphology or cell proliferation in the small and large performed on categorical variables. intestine after 14 days treatment. Results: Study participants, n = 238 (10M, 228F) had a mean Conclusion: Our results show that human-derived L. reuteri age of 33.6 7.7 yr. 3 of 5 consumer characteristics varied strains MM2-3 and MM4-1A rapidly colonize all segments of

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E22 the pig GI tract and persist at least 4 days after treatment Background: Dietary pattern of healthy schoolchildren from withdrawal. Colonization with L. reuteri has no adverse effect Pakistan is not known in detail. This information would be on gut growth and histomorphology. important to assess growth pattern and for counselling. This study is part of a nationwide HEC project. 54 Objectives: To determine the nutrition pattern of schoolchildren of low socio-economic population of Karachi and caloric FEEDING DISORDER OF INFANCY OR EARLY intake/kg/day. To plot height and weight of these children on CHILDHOOD: IS THERE ANYBODY OUT THERE? NCHS standards. Douglas G. Field, Katherine Riegel, Bridget Gibbons, Keith Methods: A cross-sectional study was conducted in selected Williams. Pediatric GI and Nutrition, Penn State Children’s public and private schools of Karachi using multistage cluster Hospital, Hershey. sampling with stratification. Stratification was performed according to type of school (public/private). Preliminary data Background: Although literature documents the etiology, of 300 schoolchildren is presented. Pretested questionnaires diagnosis, and treatment of childhood feeding disorders,there were used to interview children and to obtain information on is little agreement on how feeding disorders are defined. their dietary pattern. The children included had no history of While the Diagnostic and Statistical Manual of Mental chronic infection or frequent hospitalization and had immuniz- Disorders-Fourth Edition (DSM-IV) contains criteria for ation as per schedule. Anthropometric data was also collected. Feeding Disorder of Infancy and Early Childhood (FDIEC), The food records were subjected to USDA food exchange list. no research has examined the prevalence of FDIEC among The master files of the various forms were used as inputs to children referred for evaluation of feeding problems. Our generate necessary tables using the Statistical Package for study examines the prevalence of FDIEC in children referred Social Sciences (SPSS) for Windows 10.0. to our feeding program, classifies children with and without Results: Age was 6-18 years. Diet included rice, wheat, FDIEC in terms of feeding problems and possible etiology, vegetables, lentils, fats and oils, junk food frequently, while discusses possible modifications to the DSM-IV criteria for meat, egg, milk and fruits were taken occasionally. The caloric FDIEC and considers how these changes could affect diag- intake/kg/day for 6-9, 10-13 and 14-18 year old was 98.6 39, nosis, treatment, reimbursement for services, and future 72.2 34.3 and 48.4 27.5, respectively. Junk food was taken by research. majority in school break. Most prominent meal was lunch. Methods: We used caregiver questionnaires/clinical interviews Majority were less than 25th centile for height and weight on to determine whether each child met the DSM-IV criteria for NCHS charts. Thirty children were above 75th percentile. FDIEC and categorized them using feeding problem definitions Conclusion: Calories/kg/day were sufficient. However, com- from our previous work (Field et al, 2003). bination of carbohydrates, protein and fat were not balanced. Results: 8% of children met the DSM-IV criteria for FDIEC. Junk food was substandard. Majority children plotted less than Most children with FDIEC had food refusal while those with- 25th percentile on NCHS charts. Less than 1% were obese. out FDIEC had food selectivity by type or texture. Most children without FDIEC failed to meet the DSM-IV criterion 56 of weight loss. Some children had a problem with weight gain but did not meet the criteria for FDIEC due to the BREAST-FEEDING IN JEDDAH, SAUDI presence of a medical condition that contributed to the feeding ARABIA: CAUSES OF RELUCTANCE AND problem. METHODS OF PROMOTION Conclusions: Most children referred for evaluation of feeding Essam M. Al-Hady. Pediatric, Zgazig University, problems did not meet the definition of FDIEC under the DSM-IV Egypt-Dr. Soliman Fkeeh Hospital & Private Clinic, criteria. This creates two problems: (1) the area of childhood Jeddah, Saudi Arabia. feeding disorders has no standardized mechanism for determining which children have and which children do not have feeding During my work in the nursery and outpatient clinic in problems, making it difficult to compare children’sresponseto Dr. Soliman Fakeeh Hospital, Jeddah, 1985–1989 and sub- treatment across studies. (2) lack of a diagnostic code for many of sequently in my private practice in the next 18 years all over the children referred for treatment may affect who recieves Jeddah, I noticed that there was increased desire to artificial milk treatment, which type treatment is received and reimbursement feeding. This stimulated me to do this work. The nursing mothers for the behavioral health care provider or psychologist providing were instructed daily during rooming-in. Breast-feeding was treatment. promoted and encouraged. Its advantages to both the mother and her infant were described. The method and technique of breast-feeding and suckling were described also, especially to the 55 primipara. Assurance and support daily and even twice per day DIETARY INTAKE AND ITS IMPACT ON was done. The cases were followed up in the outpatient clinic THE GROWTH AMONG LOW SOCIOECONOMIC after discharge from the hospital. The % of cases reluctant to SCHOOLCHILDREN OF KARACHI breast-feeding was 61.8% before promotion, but it declined to Sina Aziz1, Naghma Rehan2, Umm-e-Rubab Zaidi1, Kehkashan only 2.3% after promotion and follow up. The % of success of Hosain3, Intisar A. Siddiqui4. 1Pediatrics, Dow University of breast-feeding among the reluctant cases after promotion was Health Sciences, Karachi, Pakistan; 2Medical Education, 96.3%.The causes of reluctance to breast-feeding as mentioned CPSP, Lahore, Pakistan; 3Nutrition, SIUT, Karachi; 4Medical by the mothers were: Engorged and painful breast 14.7%, No Education, CPSP, Karachi. milk in the start 11.8%, Mother is studying 11.8%, Painful and

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E23 fissured nipple 8.8%, Working mother 8.8%, Breast feeding is Conclusion: The 13C-sucrose BT can be used as a noninvasive insufficient 6.6%, Breast milk is diluted 5.8%, Artificial milk test to track inheritance in CSID family members and can be is better 5.8%, The baby was accustomed to the artificial nipple confirmed by blood DNA sequencing. 4.4%, Leave the baby with servant 4.47%, Retracted nipple 3.6%, Twins 3.6%, She is always tired 2.2%, Suckling is 58 difficult 2.9%, Absence of proper instruction 2.9%, Contraceptive pills 2.9%, That breast-feeding will increase CHARACTERISTICS OF CATHETER-RELATED her weight 2.9%, Breast size is small 2.2%, Flat nipple 2.9%, BLOODSTREAM INFECTIONS (CRBSI) IN She may be ill 1.4%, Inconvenience 0.7%. The causes of INTESTINAL FAILURE CHILDREN: IMPLICATIONS supplementary breast-feeding in the follow up successful cases FOR CLINICAL MANAGEMENT 1 2 1 were: Mother is studying 12.2%, Working mother 9%, Rinarani Sanghavi , Barbara Drews , Jane Seigal , 2 1 1 Insufficient breast milk 3.1%, Twins 3.8%, Contraceptive Pat Metcalf , Naveen Mittal . UTSW Medical Center, Dallas, 2 pills 3.1%. We realized some iatrogenic causes of reluctance to TX; Children’s Medical Center, Dallas. breast-feeding during the study, which were due to obstetric, gynecological, and pediatric causes. I succeeded in making the Background: Majority of children with intestinal failure (IF) pendulum swing back to breast-feeding. need central venous catheters (CVC) for parenteral nutrition (PN). CRBSI is poorly characterized though reported to be a 57 major cause of mortality and morbidity in IF population. We report characteristics of CRBSI with implications for clinical 13 C-SUCROSE NONINVASIVE DIAGNOSTIC BREATH management in a large case series of children with IF. TEST (BT) FOR TRACKING CSID INHERITANCE IN Methods: 101 charts of IF patients managed at our Intestinal FAMILIES Rehabilitation Clinic since May 2005 to March 2007 were 1 2 Claudia C. Robayo-Torres , Antone R. Opekun , Markus reviewed. 3 3 4 1 Kaiser , Hassan Y. Naim , Susan S. Baker , Buford L. Nichols . Results: 45 PN dependent patients had CVC for a total of 13978 1 2 Pediatrics-Nutrition, Medicine-Gastroenterology, Baylor days. 112 episodes of CRBSI (positive blood culture) yield a rate 3 College of Medicine, Houston, TX; Physiological Chemistry, of 8.1 per 1000 catheter days. Most CRBSI episodes (89, 79%) University of Veterinary Medicine Hannover, Hannover, developed in community setting during 10,924 home care days 4 Germany; Pediatrics-Gastroenterology, SUNY, Buffalo. (Group 1). 23 nosocomial episodeswere observed during 2914 inpatient days (Group 2). CRBSI rate was not statistically different Background: Congenital sucrase-isomaltase deficiency between Group 1 and 2 (8.1 vs. 7.8) Gram negative organisms (CSID) is thought to be an autosomal recessive disorder caused (67, 60%) were the most common isolates with Klebsiella by mutations of the sucrase-isomaltase (SI). We studied a family (35; 31%) as the most common to be followed by Enterococci with 2 CSID patients, using a 13C-sucrose BT and confirmed the (12, 10%); Enterobacter (7,6%); and E. coli (4, 3.5%). Common findings by sequencing the SI gene from blood DNA. gram positive isolates were: coagulase- negative staph (CNS) Methods: A family of 5; 2 CSID siblings with sucrase levels of 0 (18, 16%), and Staphylococcus aureus (6, 5%). Candida was and 1.4 U/g p (1F:1M, 3:2 yr) 2 parents and 1 sibling (F: 11 mo) positivein19(17%)ofCRBSI.BothGroup1and2showedsimilar participated. CSID was diagnosed by intestinal biopsy enzyme pattern of isolates as seen for total group. In patients with CVC assays. Uniformly labeled 13C-glucose and sucrose; 20 mg each in femoral vein, the most common organisms were CNS and (Isotec, Miamisberg, OH) were given in 10 g Polycose (10%) Klebsiella. In patients with problems of ostomy or leaky gastro- 13 after an overnight fast. CO2 breath enrichments (every stomy tubes, the most common organisms were CNS and 15 min 9) were assayed using an infrared spectrophotometer Candida. 18 CRBSI episodes (16%) followed CVC malfunction. (POCone, Otsuka Electronics, Tokyo, Japan). The coefficient of Conclusions: CRBSI in IF population is due to wide variety of % glucose oxidation (%CGO) was used to normalize sucrose organisms though gram negative bacteria are the most common. 13 CO2 BT enrichments to adjust for individual differences. We Frequent Candida isolates in this population may reflect tested dyspeptic patients with normal biopsy enzymes to define exposure to antibiotics. Factors (nosocomial vs. community; lower levels of normal (100% CGO). DNA was isolated from femoral line, leaky ostomy bag or gastrostomy tube) does not blood using QIAamp DNA Mini Kit (QIAGEN) for PCR and select out a narrow group of causative organisms. These obser- sequencing (MegaBACE 1000 capillary sequencer, GE Health- vations may help decide the empirical choice of antimicrobials. care). Results: The CSID patients had CGO below 100%; father and 59 younger sibling also were below 100%. Mother was above 100%. Sequencing showed that the CSID patients have three CAUSTIC INGESTION: ESOPHAGEAL DAMAGE AND point mutations with amino acid substitutions, two are silent NUTRITION STATUS mutations V15F and A231T which have no consequence on Carmen A. Sanchez1,3, Alfredo Larrosa1,2, Edgar Va´squez3, function; but they both have a third mutation G1073D that Francisco Larios4, Antonio Cha´vez4. 1Gastroenterology and represents a single null allele consistent with dominant inheri- Nutrition, Hospital de Pediatria, Guadalajara, Mexico; tance from the father. Discussion: This mutation supports the 2Unidad de Investigacio´n en Epidemiolog´ıaCl´ınica, IMSS, BT findings and suggests a dominant mechanism of CSID Guadalajara, Mexico; 3Instituto de Nutricio´n Humana, inheritance in this family. Universidad de Guadalajara; 4Surgery, Hospital de Pediatria.

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Introduction: Accidental caustic ingestion (ACI) in children of the snare loop. The snare loop is then tightened across the may cause esophageal burns that lead to complications such as diameter of the bolster, thus compressing and collapsing it. The dysphagia, esophageal strictures and impaired feeding. snare, PEG tube and endoscope are then pulled up the esophagus Aims: To evaluate the association of the esophageal damage of as a unit, in a retrograde fashion. As a safety precaution, the children who suffered an ACI with the nutrition status and the (external) length of the PEG tube is kept long to allow pulling the energy and macronutrient intake. tube back into the stomach, if needed, in case it proves difficult to Methods: n = 94. Design: cross-sectional. Independent vari- pass the lower esophageal sphincter. Following PEG tube ables: clinical data. Dependent variables: nutrition status, energy removal, a skin-level gastrostomy tube is placed under direct and macronutrient intake. Anthropometry (standardization, refer- endoscopic visualization. We anticipate fewer stoma-related ence patterns: Frisancho and CDC 2000) and 24-hour recall were complications such as gastrostomy tract disruptions, and believe performed. this method for endoscopic PEG tube removal is safe, nontrau- Results: 37.2% females, mean age 75.2 months. The most matic, and well tolerated. frequent symptoms: salivation, vomiting and oropharyngeal burns. 7.7% had first-degree, 76.9% second-degree and 7.7% 61 third degree burns. 48.9% developed esophageal stricture. The cases with the severest esophageal burns were associated with UTILITY OF SACROSIDASE (SUCRAID) esophageal stricture (P = 0.004) and ingestion of alkaline pro- SUPPLEMENTATION IN TODDLER’S DIARRHEA ducts (P = 0.027). Dysphagia was associated with esophageal Riad M. Rahhal, Warrem Bishop. Pediatric Gastroenterology, stricture (P < 0.001). Nutritional status: cases <2 SD: height University of Iowa, Iowa City. for age 5.3%, weight for height 4.3%, weight for age 6.4%, middle upper arm circumference 8.5%, arm muscle area 6.4%, Chronic nonspecific diarrhea in children, also known as tod- total arm area 4.3%, and arm fat area 1.1%. Frequency of dler’s diarrhea, is a frequently encountered disorder in clinical overweight and obesity: 15.3% and 12.5%, respectively. The practice. It tends to cause significant parental anxiety and intake of energy, carbohydrate and the intakes as a percentage of frustration leading to frequent health care visits. We investi- DRIs were significantly lower in children with chronic malnu- gated the usefulness of sacrosidase (Sucraid) supplementation trition than in the group with normal nutrition status (P < 0.05). in children with toddler’s diarrhea. The primary outcome was The presence of stricture and dysphagia was associated with the the proportion of patients who clinically responded to sacrosi- used of blended or polymeric diets (P < 0.05). dase supplementation. Secondary outcome measures included Conclusions: Despite the high proportion of esophageal stric- safety and potential adverse effects. Forty children, 1 to 6 years ture and dysphagia, the frequency of acute and chronic mal- of age, with chronic diarrhea were evaluated at our outpatient nutrition was quite low. A lower intake of energy and carbo- subspecialty clinic. Medical history, examination and workup in hydrate was identified in children with growth retardation. 12 patients suggested the diagnosis of toddler’s diarrhea. Defe- Overweight and obesity was three times more frequent than cation patterns were obtained prior to treatment and while on malnutrition. supplementation. Twelve patients were enrolled of which 8 completed this open prospective trial. Three patients did not 60 satisfy our criteria based on low baseline stool frequency and consistency characteristics and two families failed to provide A NOVEL NONTRAUMATIC METHOD FOR THE the needed daily diaries and were excluded. Of the remaining REMOVAL OF PERCUTANEOUS ENDOSCOPIC patients, 3 of 7 (43%) were clinical responders. None of the GASTROSTOMY TUBES IN CHILDREN patients reported any adverse effects. Sacrosidase supplement- Ashish N. DebRoy, Riad M. Rahhal, Warren P. Bishop. ation demonstrated a potential benefit in a subset of children Pediatric Gastroenterology, University of Iowa Children’s with toddler’s diarrhea by decreasing stool frequency and Hospital, Iowa City. improving stool consistency. This may be due to excessive sucrose in children’s diet or to Percutaneous endoscopic gastrostomy (PEG) feeding tubes have unrecognized partial sucrase deficiency. A larger scale study proven to be a safe and effective mode of enteral nutrition in with longer patient follow up is needed to further assess the children. Various methods have been described for the removal of benefit of such an intervention. PEG tubes following maturation of the gastrocutaneous tract. These methods include retrograde endoscopic removal with 62 large-diameter PEG tubes or by traction with small- and large-diameter tubes equipped with collapsible internal bolsters. PEDIATRICIANS’ ABILITY TO DISCRIMINATE Complications associated with PEG tube removal by traction THE WEIGHT STATUS OF CHILDREN: RESULTS include stoma-related complications such as gastrostomy tract OF A PHOTOGRAPH SURVEY disruptions and gastric separation from the abdominal wall. Such Jeannie Huang, Golnaz Golnari, Edward Walker Gallego, Kate complications are infrequent but may lead to significant patient Galvan, Christina Briones, Jennifer Tamai, Van Ong, Elizabeth morbidity when they occur. We describe a novel nontraumatic Yu, Karen Becerra. Pediatrics, University of California, San method for endoscopic removal of small-diameter PEG tubes Diego. (12-French) in children. The method involves grasping the collapsible internal bolster of the PEG tube with a polypectomy Objective: To assess the ability of pediatricians to determine snare during endoscopy. The pediatric polypectomy snare is the weight status of photographed children and ascertain weight deployed, with the plane of the bolster perpendicular to the plane assessment practices among pediatricians.

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Method: Invitations to participate in a Web-based survey were Conclusions: The prevalence of anemia it was 81.1%, to wish distributed to a convenience sample of US pediatricians. was correlation with nutritional state, principally to global and Respondents were asked to identify the weight status of photo- acute MNT, but not to use of M’C, neither to presence of IP graphed children and their ideal body types for various age groups. Participants were also asked about their weight assess- 64 ment practices, and personal and career demographics. Results: 3,488 pediatricians participated. 11% of respondents AGE- AND ETHNIC-SPECIFIC ELEVATION OF ALT reported using non-objective criteria to assess obesity in their AMONG OBESE CHILDREN AT RISK FOR patients; 64% reported using body mass index (BMI) as their NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) objective criterion. However, 35% of pediatricians calculated BMI ‘‘only when concerned’’ and only 31% of respondents Daniel H. Leung1,2, Kent Williams3, J. K. Fraley2, knew the NCHS BMI definitions of at risk for overweight and William J. Klish2. 1GI, Children’s Hospital of Philadelphia, overweight in children. Overall, participants correctly identified Philadelphia, PA; 2GI, Baylor College of Medicine, Houston, the weight status of 58% of presented photographs and 43% of TX; 3GI, Vanderbilt School of Medicine, Nashville, TN. photographed overweight or at risk for overweight children. In general, participants were more likely to identify the correct Background: In light of reported ethnic differences in the ideal body type for older children than for young infants. prevalence of cryptogenic cirrhosis or NAFLD the objectives Pediatricians who reported fewer than 5 years of work experi- of this study were to: 1) determine if Hispanic children demon- ence were more likely than more experienced colleagues to strated a higher incidence of ALT elevation, 2) establish at what correctly assess weight based on appearance, know NCHS BMI age significant ALT elevation occurred, and 3) explore the definitions of weight status and use objective criteria to judge association between ALT elevation and fasting triglyceride/ weight. insulin levels, or degree of obesity. Conclusions: Practicing pediatricians are inadequately able to Methods: A cohort of 134 obese children and adolescents (BMI correctly identify children’s weight status by non-objective >95%) of different ethnic backgrounds (Non-Hispanic White, criteria. Therefore, objective criteria for weight status should Black, Hispanic) was retrospectively analyzed. ANOVA was be applied regularly in the clinical setting to determine risk for used to detect statistically significant differences in mean BMI, nutritional problems, particularly in regards to assessing for ALT, triglyceride and fasting insulin between the ethnic groups obesity. Recent training may improve knowledge and perform- and by gender. ALT levels were categorized into ‘‘high risk’’ ance of recommended weight assessment methods. levels (>45 or greater than 1.5x the ULN of reference lab values) and ‘‘normal risk’’ levels (<45 or less than 1.5x the 63 ULN) for developing NAFLD. Chi-square and Fisher exact tests were used to determine if a significantly higher proportion of ANEMIA, COW’S MILK, UNDERNUTRITION, AND ‘‘high risk’’ ALT levels fell within a specific age, ethnicity, or INTESTINAL PARASITISM IN INFANTS gender. A Pearson correlation was performed to determine Carlos A. Velasco1,2, Angela M. Olarte1. 1Pediatrics, associations of BMI, ALT, triglyceride, and fasting insulin. Universidad del Valle, Cali, Colombia; 2Universidad Libre, Results: ALT was significantly different among the 3 ethnic Universidad Autonoma de Occidente, Cali. groups (P = 0.019). 60% of Hispanics, almost all of whom were of Mexican descent by report had ‘‘high risk’’ ALT levels Introduction: Anemia in infants is an important cause of compared with 12% of whites and 8% of Blacks. Hispanic morbimortality; it has been identified for multiple causes like boys presented with ‘‘high risk’’ ALT levels much earlier. There undernutrition (MNT), use of milk’scow(M’C) and the pre- was no statistically significant association between ALT sence of intestinal parasites (IP). elevation and fasting triglycerides, insulin, or degree of obesity. Objective: To determine in 120 infants of the Hospital Uni- Conclusion: Obese Hispanic children, especially boys, not only versitario del Valle, Cali, Colombia, if MNT, use of M’Cor have significantly higher ALT levels, but present with ‘‘high presence of IP are anemia causes. risk’’ levels at an alarmingly earlier age. BMI, fasting insulin Materials and Methods: Descriptive observational study, in levels and triglyceride levels showed no strong association with 120 infants to whom they took weight (W), height (H), hemo- ALT elevation. ALT levels should be considered among young globin (Hb), tool test, age (A), gender and nutritional status. It was obese Mexican-Hispanic males for screening of risk of NAFLD. global MNT when it was a deficit to W/A > 10%, chronic MNT with H/A > 5% and acute MNT with W/H > 10%. Anemia was Pancreas/Cystic Fibrosis considered when Hb it was < 11 g/dl. Other information was: use of M’C, and IP. The outcomes was expressed like %, mean and 65 SD; with a statistical analysis to include the t test, linear regression and correlation, being significant a P < 0.05. DETECTION OF SBDS PROTEIN ABUNDANCE IN Results: We include 120 children, with age 8.75.8 months, PERIPHERAL BLOOD LEUKOCYTES OF PATIENTS 54.2% females, with global MNT in 69.3%, chronic MNT in WITH SHWACHMAN DIAMOND SYNDROME (SDS) 55% and acute MNT in 44.2%, with anemia in 81.1%, with use Peter Durie1, Wan F. Ip1, Akiko Shimamura2, Annie Dupuis1, of M’C in 94.1%, and IP in 20.5%. It was correlation between Elena Nicolis3, Marco Cipolli3, Johanna M. Rommens1. 1The anemia, global MNT (P = 0.003) and acute MNT (P = 0.035), Hospital for Sick Children, Toronto, ON, Canada; 2Children’s but not with chronic MNT (P = 0.088), neither with use M’C Hospital, Boston, MA; 3Azienda Ospedaliera di Verona, Verona, (P = 0.367), neither presence the IP (P = 0.392). Italy.

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We are studying the relationship between SBDS genotypes and Results: A total of 21 children were enrolled in the study. SBDS protein abundance. To achieve this objective we are Eleven patients submitted stool samples both on and off developing an ELISA method, using a polyclonal anti-SBDS enzymes, while ten patients submitted a single stool sample antibody (C-terminus), to detect SBDS protein abundance in on enzymes. For all samples collected, the FE concentration leukocyte lysates. The quantity of the SBDS protein is expressed was less than 200 mg/g of stool. The FE levels of stool samples as a ratio relative to endogenous tubulin levels (SBDS/TU). Anti- obtained while patients were taking supplemental enzymes did SBDS antibody tested with leukocyte extracts from healthy not differ significantly from those collected off enzymes. subjects (n = 16) showed specific immunoreactivity by ELISA. Conclusion: The polyclonal antibody test system for human The interassay CV ranged from 2.5 to 13.7%. SBDS absorbance elastase in stool does not detect porcine extracts present in at 450 nm was linearly correlated to the amount of diluted exogenous pancreatic enzymes. This test system can be used leukocyte lysate (slope = 0.52, r2 = 0.967). The best fit slope of to accurately determine the exocrine pancreatic function of the SBDS dilution curves for 15 obligate heterozygotes children taking supplemental pancreatic enzymes. (slope = 0.31) differed significantly from that of 14 SDS patients carrying the common SBDS mutations (slope = 0.04. The mean 67 SBDS/TU ratio for healthy controls was 0.985 (range 0.799 to 1.223). The mean SBDS/TU ratio for 1 heterozygote carrying the HIGH PREVALENCE OF PANCREATIC early truncation allele and 6 carrying the splice mutation allele INSUFFICIENCY IN CHILDREN AND ADOLESCENTS was 0.6120.09 (range 0.459 to 0.638). SDS patients carrying WITH TYPE 1 DIABETES MELLITUS 1,2 1,2 2 SBDS mutations: K62X, S41fs17, splice sites, and rearrangement Pamela Jofre´ , Ilse Gonzalez , Marcela Gonzalez , 2 2 2 1 (R) showed a low SBDS/TU ratio (0.08, range 0 to 0.20, Cristina Semler , Marcelo Tapia , Marta Arriaza . Pediatr´ıa, 2 P < 0.0001). Variable SBDS abundance was observed in patients Universidad de Valpara´ıso, Vin˜a del Mar, Chile; Dr Gustavo carrying missense mutations with SBDS/TU ratios ranging from Fricke Hospital, Vin˜a del Mar. values similar those with common mutations (Q153R, 0.035) to ratios within the reference range for healthy controls (K33E, 0.88 Background: Due to close anatomical position between the and V130L, 0.74). To conclude, we have developed a simple and endocrine and the exocrine system cells in the pancreas, some specific ELISA for measuring SBDS protein in leukocyte lysates. interactions could be expected in these two different types of The SBDS-ELISA test may serve as a tool to discriminate SDS cells. Diabetic patients present gastrointestinal complaints of carriers, for investigating SBDS protein expression in relation unclear origin, unexplained fluctuations in blood sugar, or loss to the heterogeneous SDS phenotypes and in patients with of weight. Pancreatic exocrine insufficiency should be included SDS-like manifestations. in differential diagnosis. The aim of this study was to screen Funded by the Shwacman-Diamond Syndrome Foundation. children and adolescents with type 1 diabetes mellitus (DM) for pancreatic exocrine insufficiency. 66 Methods: We studied 46 DM 1 patients. The ages ranged between 3 to 16 years. An immunoenzymatic method, Elastase SPECIFICITY OF THE POLYCLONAL ANTIBODY Fecal 1 was used for diagnosis of pancreatic insufficiency (PI) TEST SYSTEM FOR HUMAN ELASTASE IN STOOL (ScheBoTech, Wettenburg, Germany). According to the 1 1 2 Cary M. Qualia , Juan F. Villalona , Clement Ren , Thomas M. company’s instruction booklet, it is accepted that levels of 1 1 2 Rossi . Pediatric Gastroenterology, Pediatric Pulmonology, <100 mg/g, 100–200 mg/g, and >200 mg/g were considered as University of Rochester Medical Center, Rochester, NY. severe pancreatic insufficiency, mild pancreatic insufficiency, and normal pancreatic function, respectively. We excluded Background: Elastase is a proteolytic enzyme secreted by enteropathies like active celiac disease. exocrine pancreatic tissue. Fecal elastase (FE) concentration Results: In 14 of 46 patients FE-1 was lower than 100ug/g has been shown to be a reliable indicator of exocrine pancreatic (30,4%) and between 100 and 200 mg/g (15,2%) in 7. The global secretion. FE levels greater than 200 mg/g of stool are consistent prevalence of pancreatic insufficiency was 45,6%. In patients with pancreatic sufficiency. Both monoclonal and polyclonal with normal pancreatic function, their clinical features were age antibody test systems for the detection of FE exist. While the (mean SD) 9,9 3,1 years, BMI 17,95 2,28 kg/m2, HbA1c monoclonal antibody test system utilizes a single antibody that 7,8 %. FE 1 was 88,0 SD, age 11,1 3,11 years, BMI binds to a specific epitope of human pancreatic elastase, the 19,52 kg/m2 and HbA1c 9,2% in PI patients. polyclonal system utilizes four different antibodies that bind to Conclusions: The prevalence of pancreatic insufficiency was a synthetic peptide sequence contained within human pancreatic high in these groups. Patients with PI had poor metabolic elastase. The purpose of this study was to determine whether the control. We suggest that evaluation of the exocrine function antibodiesemployedbythepolyclonaltestsystemcross-reactwith should be done in diabetic patients porcine elastase contained in supplemental pancreatic enzymes. Methods: Children age 0–18 years taking supplemental pan- 68 creatic enzymes were eligible for enrollment. Stool samples were collected from all patients while they were ingesting CHILD-FRIENDLY DOSING OPTIONS FOR supplemental pancreatic enzymes. A proportion of patients PANCREATIC ENZYME PRODUCTS (PEPS): then discontinued their supplemental enzymes for four days WHAT FOODS CAN PEPS BE SPRINKLED ON? and a second stool sample was collected. All stool samples were Marco Anelli1, D. Shepherd2, R. Foresti1, D. Sica1, tested by the polyclonal antibody test system (Bioserv, Rostock, Marian Cutler2. 1Eurand SpA, Milan, Italy; 2Eurand Inc., Germany) for FE concentration. Vandalia, OH.

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For very young children being treated with pancreatic enzyme no significant differences in the frequency or type of AEs products (PEPs) for exocrine pancreatic insufficiency (EPI), it is between EUR-1008 and placebo. No patient discontinued from common practice to open the PEP dosage units and sprinkle the study due to an AE. In this phase 3 study, EUR-1008 was their contents on a small amount of food. Applesauce is the most safe, well tolerated and effective in CF patients, with clinically commonly used food because its acidic pH preserves the coat- and statistically significant improvements in CFA, CNA, and ing of gastroprotected formulations, preventing the degradation EPI signs and symptoms in the absence of concomitant treat- of the PEP enzymes in the stomach. Since the coating of ment affecting GI motility and pH. The therapeutic benefit of most enteric coated formulations starts to dissolve at pH values EUR-1008 was seen even in patients with high CFA values. >5.5, we hypothesized that EUR-1008 microtablets, a novel, enteric-coated PEP, could be sprinkled on foods with pH 5. 70 We tested the resistance of three batches of EUR-1008 microtablets against a series of commercially available and home- cAMP IS AN IMPORTANT SIGNALING MOLECULE IN made baby and infant foods with pH 5. We considered as THE ABERRANT CALCIUM SIGNAL ASSOCIATED ‘‘suitable for sprinkling’’ those foods in which EUR-1008 WITH PATHOLOGIC PANCREATIC ZYMOGEN microtablets could remain for 1 hour without significant ACTIVATION AND PANCREATITIS deterioration of the gastroresistant coating. Ten of 11 (91%) Sahibzada U. Latif2, Wayne M. Grant1, Ahsan U. Shah1, foods with pH 5, including both homemade recipes, proved to Sohail Z. Husain1. 1Pediatrics, Yale University, New Haven, CT; be suitable for the sprinkling/mixing of EUR-1008 microtab- 2Internal Medicine, Michigan State University, East Lansing, lets. In cases where the ‘‘universally recommended’’ applesauce MI. is not a feasible option for administering PEPs to very young children, several other commercially available foods—and even Intra-acinar zymogen activation is an early and critical feature homemade recipes—can be effectively used as an alternative. of acute pancreatitis. High sustained calcium elevations within the pancreatic acinar cell precede pathologic zymogen acti- 69 vation. However, the determinants of the calcium signal are not clear. We have previously shown that cAMP sensitizes the SAFETY AND EFFICACY OF EUR-1008, A NEW pancreatic acinar cell to zymogen activation. In this study, PANCREATIC ENZYME PRODUCT (PEP), IN CYSTIC we examined the role of cAMP in shaping the dynamics of FIBROSIS (CF) PATIENTS WITH EXOCRINE the calcium signal. We hypothesized that cAMP regulates intra- PANCREATIC INSUFFICIENCY (EPI) acinar calcium channel opening in response to calcium-evoking James Heubi1, S.R. Boas2, K. Blake3, S.Z. Nasr4, M.S. Woo5, 6 7 8 9 agonists. In these experiments, isolated acinar cells were loaded G.R. Graff , K.A. Hardy , R. Amaro-Galvez , M. Latino , with the calcium dye fluo4 and imaged using a confocal laser C. Lee10. 1CCHMC, Cincinnati, OH; 2Chicago CF Care, 3 4 scanning microscope. They were stimulated with the calcium- Glenview, IL; Nemours, Jacksonville, FL; University of evoking agonist carbachol (1 mM) in the absence or presence of Michigan, Ann Arbor; 5Children’s Hospital, Los Angeles, 6 7 the cAMP analog 8-Br-cAMP (100 mM). We noted that the rise CA; Pennsylvania State Hospital, Hershey; Children’s time after carbachol stimulation was reduced by 55% Hospital, Oakland, CA; 8Texas University, Tyler; 9 10 (P < 0.005) in the basolateral region of the cell and to a lesser Eurand, Milan, Italy; Eurand, Vandalia, OH. degree in the apical region. In addition, the slope of the calcium rise was increased 2.8 and 1.9 fold in the basolateral and apical This phase 3, randomized, double-blind, placebo-controlled regions, respectively, with cAMP pretreatment (P < 0.01). trial evaluated the efficacy and safety of EUR-1008, a zero- Furthermore, the speed of the apical-to-basolateral calcium overfill, porcine-derived PEP, in CF patients with EPI. Patients wave increased from 8 to 21 mm/sec (P < 0.05). The intracellu- (n = 34) had confirmed CF and EPI, age 7 years, fecal elastase lar calcium channel inhibitor dantrolene abrogated the increase <100 ng/g, good nutritional status and weight 70 kg. Patients in wave speed (P < 0.05). No differences were noted in the peak with a high coefficient of fat absorption (CFA) (>80%) were calcium response in the two regions. These data suggest that included. No drugs affecting gastric pH or motility were cAMP affects the calcium signal primarily in the basolateral allowed. After open-label dose titration, patients were random- region, where the ryanodine receptor is concentrated. Further, ized to one week of EUR-1008 or placebo. Following another the effects of cAMP on the acinar cell calcium wave appear to open-label normalization, they crossed over to the alternative be dependent on ryanodine receptor opening. We conclude that treatment. The primary endpoint was change in CFA following cAMP appears to regulate ryanodine receptor calcium opening administration of EUR-1008 vs. placebo. Secondary endpoints in pancreatic acinar cells. included change in coefficient of nitrogen absorption (CNA), fat-soluble vitamins, and EPI signs and symptoms. Safety was 71 also evaluated. In 32 evaluable patients (mean age 15.4 y), CFA and CNA values significantly increased following treatment PREVALENCE OF ELEVATED LIVER FUNCTION with EUR-1008 vs. placebo (P < 0.001). EUR-1008 was associ- TESTS IN CHILDREN WITH CYSTIC FIBROSIS ated with improved vitamin K status and improvements in EPI DIAGNOSED BY NEWBORN SCREEN signs and symptoms, including a significant reduction in stool Samantha A. Woodruff1, Marci Sontag2, Frank Accurso2, frequency and fewer soft/watery stools. EUR-1008 improved Ronald J. Sokol1, Michael R. Narkewicz1. 1Pediatric EPI signs and symptoms even in patients with CFA values Gastroenterology, Hepatology and Nutrition, 2Pediatric >80% on placebo. EUR-1008 was safe and well-tolerated, with Pulmonology, The Children’s Hospital, Denver, CO.

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Background and Methods: Abnormal hepatic enzymes are tion of cytokines which prime (IL5, IL-13, and eotaxin) and present in approximately one third of all cystic fibrosis patients. sustain (eotaxin and RANTES) eosinophilic inflammation; 2. Current guidelines call for yearly screening of cystic fibrosis CCR3 and EDN (eosinophil derived neurotoxin) upregulation patients with LFTs, however, once abnormalities are identified confirm eosinophil presence; 3. Markers of non-TH2 mediated they are of uncertain significance, often triggering an evaluation inflammation were not upregulated (IL-17 and IFN-g); 4. for liver disease. We prospectively analyzed 383 patients with Periostin upregulation suggests its role in tissue remodeling cystic fibrosis identified by newborn screen since 1982. We as proposed to occur in EE; 5. Down-regulation of CCL17, a assessed AST, ALTand GGTP, evaluated at the annual well visit chemokine involved in allergic inflammation, is previously not (to avoid the effect of intercurrent illness) to describe the reported in EE. prevalence of abnormalities in these tests. Our goal was to Future: These results advance our understanding of EE establish prevalence and frequency of enzyme abnormalities, pathogenesis and could be potential biomarkers for EE. and to assess if degree and persistence of abnormalities Further studies, including analysis in treated EE children, are correlated with development of advanced liver disease. underway. Results: Kaplan Meier estimates of the percentage of children with a single (first) or 2 or more (second) values of AST, ALT and GGTP, 1.5X ULN, 2X ULN and 3X ULN were determined Relative Quantiﬁcation (fold difference) (see Table). Children with known liver disease were more likely Control (n = 15) EE untreated (n = 15) P to have abnormalities in hepatic enzymes, but many children with cirrhosis and severe liver disease had no abnormalities in Eotaxin 1 3.2 21.84 0.037 hepatic enzymes. Eotaxin 2 1.7 15.47 0.0003 Conclusions: Abnormal AST, ALTand GGTare common in CF. Eotaxin 3 4.3 225.1 0.012 ALTwas most commonly abnormal infrequently associated with CCR3 5.5 304 0.032 advanced liver disease. Given the high prevalence of abnormal EDN 8.6 605 0.042 AST, ALT and GGT, the significance and approach to patients RANTES 4.34 1.64 0.038 with abnormal values needs to be prospectively evaluated. CCL17 1.75 0.66 0.0077 IL-5 7.1 979 0.046 Speculation: Abnormal ALT may indicate hepatic steatosis. IL-13 5.4 748 0.02 IL17 0.43 0.4 0.39 IFN-g 1.48 1.7 0.69 Percent at 250 mo Any abnormal 1.5X ULN 2X ULN Periostin 5.1 324.1 0.0038 with abnormal (1/2 or more) (1/2 or more) (1/2 or more) 2 outliers were omitted from analysis. AST 63%/40% 19%/25% 40%/0 ALT 93%/85% 50%/42% 32%/31% GGT 39%/19% 25%/14% 20%/4% 73 A GENOME-WIDE ASSOCIATION STUDY IDENTIFIES T CELL LYMPHOMA BREAKPOINT1 AS A PLENARY SESSION I NOVEL SUSCEPTIBILITY GENE IN FRIDAY, OCTOBER 26, 2007 PEDIATRIC ONSET CROHN’S DISEASE Subra Kugathasan1, Marla Dubinsky2, Lee Denson2, 8:30 AM Steven Guthery2, Nicholas Peterson1, Richard Grant2, 2 1 2 72 Jessica Lee , Tao Wang , Anne Griffiths , Salvatore Cucchiara2, Gitit Tomer2, Nicholas Schork2, Ulrich Broeckel1. BIOMARKERS OF TISSUE INFLAMMATION IN 1Pediatrics, Medical College of Wisconsin, Milwaukee; EOSINOPHILIC ESOPHAGITIS (EE) 2International Pediatric IBD Genetic Study Group, Milwaukee. M. Davis, F. Tuana, W. Yao, M. Kaplan, S. Gupta. Indiana University, Indianapolis, IN. In addition towell confirmed NOD2 risk in Crohn’s disease (CD), recent genome-wide association (WGA) studies revealed IL23R Background: EE is becoming more prevalent among children and ATG16L as risk in adult onset ileal CD. Early onset risk genes and adults. Better understanding of its pathogenesis will help in CD are not known. Colon is the most common disease location define novel therapies which currently are limited. of pediatric CD. We performed a WGA (GeneChip Human Aim: To study biomarkers of inflammation in EE. Mapping 500K Affymetrix) to identify early onset CD genes. Methods: mRNA levels of various inflammatory proteins were 123 colon only (macroscopic colonic involvement-Montreal measured by RT-PCR technique on endoscopically obtained classification, L2 with L4 and perianal modifier) pediatric CD esophageal mucosal biopsies from controls and untreated cases were compared with 100 age matched controls along with EE children. 490 older controls (mean age of 65 yr) where the risk of Results: 30 children were analyzed; 15 controls (9 males, mean developing CD in future is minimal. Using a single point analysis, age 10.82 years); 15 EE (10 males, mean age 9.94 years). Results we identified few genome-wide significant (P < 107) and many were compared between the groups by student t-test (Table). suggestive (P < 104 to 7) associations. Although few of the hits Conclusion: Untreated EE patients demonstrate an obvious failed to replicate, an SNP located in the region of chromosome molecular signature of eosinophilic inflammation: 1. Upregula- 6q21 encoding the gene T-cell lymphoma breakpoint1 (TCBA1)

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E29 was replicated in independent cohorts. Significant association PLENARY SESSION II 3 (P =10 ) in another case-control (545 CD cases, 456 controls) FRIDAY, OCTOBER 26, 2007 was seen (minor allele frequency 9% cases, 4.5% controls), while the variant allele was over transmitted to affected offspring 10:30 AM (198 colonic CD trios, P < 0.02). Fine mapping revealed more 75 Fellow Research Award markers contributing to CD susceptibility within this loci and haplotype analysis support strong linkage disequilibrium extend- PRESENCE OF TNFR PROTECTS FROM NEOPLASTIC ing two blocks within TCBA1 gene. A constructed 3 marker TRANSFORMATION FOLLOWING CHRONIC haplotype (GAG) showed most significant risk (P =0.002)with EXPERIMENTAL COLITIS the frequency of 77%. This risk is only increased in colon only CD Ilana S. Fortgang1, Karen Edelblum2, Tatsuki Koyama3,M.K. but not associated with ulcerative colitis (n = 212). TCBA1 is Washington4, D.B. Polk1,2. 1Pediatrics, Division of GI, 2Cell & expressed in thymus and T-cells. Disruption of TCBA1 has been Developmental Biology, 3Biostatistics, 4Pathology, Vanderbilt known to be associated with T cell lymphomas and leukemias. University, Nashville, TN. We report a new discovery of risk gene (TCBA1) in colonic CD of early onset. The association of pediatric CD with novel Background and Aims: Tumor necrosis factor (TNF) is a pro- gene TCBA1 may have potential implications for disease patho- inflammatory cytokine active in the pathogenesis of inflamma- genesis. tory bowel disease (IBD) and experimental colitis. The two TNF receptors (R) exert opposing actions on apoptosis and prolifer- 74 Young Faculty Clinical Investigator Award ation in intestinal epithelial cells. Given the associations of IBD, cancer and TNF, we sought to understand the differential roles of YOUNG AGE OF IBD ONSET INCREASES THE RISK TNFR in a colitis-associated colon carcinoma (CAC) model. OF IBD TO RELATIVES: ANALYSIS INCLUDING Methods: Six-week-old C57Bl/6 (WT) mice, TNFR1/, 367 LARGE UTAH PEDIGREES TNFR2/, TNFR1/2/, and TNF/ mice were given Stephen Guthery1, Richard Kerber2, Richard Pimentel3, an intraperitoneal (ip) injection of azoxymethane (AOM) Geraldine Mineau2. 1Pediatrics, 2Oncological Sciences, (12 mg/kg body weight) followed by three 5-day courses of Huntsman Cancer Institute, 3Huntsman Cancer Institute, 2-2.5% dextran sulfate sodium (DSS) in drinking water over University of Utah, Salt Lake City. 11 weeks when all animals were sacrificed. Controls included mice given ip PBS followed by DSS or ip AOM without DSS. Background: Early age of IBD onset may be due to increased Outcomes measured included weight, hematochezia, mortality genetic load or unique environmental exposures. The Utah and colon length. Colonic mucosal injury and tumors were scored Population Database (UPDB) is a genealogical database with by a pathologist blinded to treatment groups. / 9 million records dating to the mid-18th century, and is a Results: After the second course of DSS, TNFR1/2 mice novel resource for studying the familiality of disease. We tested treated with PBS/DSS (P/D) experienced 50% mortality and the hypothesis that the risk of IBD to relatives increases as age TNFR1/ mice treated with either P/D or AOM/DSS (A/D) of onset in the proband decreases. experienced 25% mortality. Other genotypes had 100% survival Methods: We compared the risk of IBD to relatives of cases to the regardless of treatment. All WT mice treated with A/D developed risk of IBD to relatives of controls. We defined IBD as a adenomas, and 50% of TNFR1/2/ mice treated with A/D ‘‘possible’’ or ‘‘probable’’ case based on the frequency of health- developed intramucosal CAC. All TNFR1/ mice treated with care encounters with appropriate ICD-9 codes (555.0-556.9). We A/D developed CAC with invasive CAC in 1/3. Of TNFR1/ stratified IBD cases by age of onset. We calculated stratified odds mice treated with P/D, 67% developed invasive CAC. Despite ratios using the Mantel-Haenzsel method. high injury scores compared to WT, only 33% of TNF/ mice Results: We identified 1,093 cases of Crohn’s disease (CD) and treated with A/D developed adenoma, and none had CAC. 896 cases of ulcerative colitis (UC). The risks of CD, UC, and Conclusions: Absence of TNF signaling enhances epithelial IBD were all increased in 1st degree relatives of probands cell injury, and loss of TNFR1 signaling corresponds with in compared to relatives of controls. Among IBD cases (CD+UC), vivo neoplastic transformation. These findings support the role the magnitude of the increase in risk was much larger in of TNF and its receptors as discrete and important mediators of relatives of individuals with early onset IBD (odds ratio, colon epithelial cell response to injury in development of CAC. 11.9; 95% CI 4.0 to 42.2) compared to relatives of cases with later onset IBD (odds ratio, 3.3; 95% CI 1.7 to 6.5). The 76 Fellow Research Award difference between these odds ratios was statistically significant (test of homogeneity P = 0.037). We cannot exclude possible SIGNALING VIA THE TOLL-RECEPTOR detection bias. We identified possible high-risk IBD families in ASSOCIATED ACTIVATOR OF INTERFERON (TRIF) which the proportion of affected individuals was >2-fold the PATHWAY PROTECTS FROM THE DEVELOPMENT general population. 367 Utah families, ranging in size from OF COLITIS IN A MURINE MODEL OF 1,180–63,592 (median 7,112) members, met these criteria. INFLAMMATORY BOWEL DISEASE Conclusions: Early age of IBD onset may modify the risk to Keith J. Breglio1, Masayuki Fukata2, Daisy Conduah2, relatives. The biological correlates underlying this differential Anli Chen2, Tyralee Goo2, David Hsu2, Maria T. Abreu2. risk should be further explored. To address possible bias, we 1Division of Pediatric Gastroenterology, Department of will 1) link an additional 8,000 possible IBD cases to UPDB, Pediatrics, 2Inflammatory Bowel Disease Center, Division of and 2) validate our case ascertainment methods by chart Gastroenterology, Department of Medicine, Mount Sinai review. Medical Center, New York, NY.

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Introduction: Abnormal T cell responses to commensal bacteria suggests that miRNA may play important roles in other aspects are involved in the pathogenesis of inflammatory bowel disease of hepatogenesis. (IBD). Recognition of bacteria is dependent on toll-like receptors (TLR) in the intestinal mucosa, the majority which signal through the myeloid differentiation factor (MyD88) pathway. TRIF is an alternative activation pathway downstream of TLRs 4 and 3. We POSTER SESSION II tested the hypothesis that signaling via TRIF protects against the FRIDAY, OCTOBER 26, 2007 development of colitis. We used a well-established model of IBD, whereby transfer of na¨ıve CD45RBhi CD4+ T cells from wild 12:15 PM – 2:15 PM type (WT) mice into immunodeficent mice causes colitis which is driven by intestinal bacteria. Cellular/Molecular Biology + Methods: CD4 CD45Rbhi na¨ıve T cells were isolated from TRIF/ and WT spleens. The na¨ıve T cells were adoptively 78 / transferred to RAG1 mice. The ability to induce colitis was THE ROLE OF TOLL-LIKE RECEPTORS 2 AND 4 IN assed via histological score and change in body weight. T cell ACUTE INTESTINAL INJURY 3 proliferation and cytokine expression were assessed via H- Charles J. Aprahamian3, Robin G. Lorenz2,4, Carroll M. thymidine and ELISA assays respectively. Harmon3, Yingkui Yang3, Reed A. Dimmitt1,3. 1Pediatrics, Results: Compared to the transfer of WT na¨ıve T cells, transfer 2Microbiology, 3Surgery, 4Pathology, University of Alabama at / of TRIF T cells resulted in a significant decrease in weight Birmingham. and increased inflammatory cells and crypt architectural dis- / tortion on histology in the recipient mice. TRIF na¨ıve T cells Introduction: Human milk and probiotics decrease the risk for exhibit increased proliferation compared to WT T cells as / necrotizing enterocolitis (NEC), presumably in part by establish- measured by 3H-Thymidine assays. TRIF T cells show ing a commensal microbiota that signals via toll-like receptors increased expression of IL-17 and IL-2 when stimulated with (TLRs). The aim of this study was to investigate to the role of toll ligands CpG and PAM respectively as compared to WT. TLR2 and TLR4 in an animal model of NEC. We hypothesized Conclusion: Signaling via TRIF on T cells plays a role in that mice lacking TLR2 or TLR4 would fail to mount a protective protection from the development of colitis. The absence of this immune response with resultant greater intestinal injury. alternative pathway may allow for signaling through the Methods: Four-week-old C57BL/6 wild-type (WT) (n = 4/ MyD88 pathway with development of colitis. These results group), B6.TLR2/, and B6.TLR4/ mice (n = 6/group) suggest a role for TLR signaling by T cells in development of underwent laparotomy with superior mesenteric artery occlu- IBD. sion for 60 minutes, followed by 90 minutes of reperfusion (I/ R). Mid-jejunal sections were taken for histopathology and 77 Young Faculty Investigator Award protein quantification by ELISA. Specific cytokine concentration was expressed as ratio of the total amount of protein in MICRORNA-223 IS REQUIRED FOR VERTEBRATE the sample (TP). Intestinal injury was scored from 0 (no injury) HEPATOBILIARY DEVELOPMENT to 4 (transmural necrosis). Parametric and nonparametric tests Joshua Friedman, Nicholas J. Hand, Zankhana R. Master, were used where appropriate; P < 0.05 significant. Randolph P. Matthews, Steven F. EauClaire. Department of Results: Both B6.TLR2/ and B6.TLR4/ mice had a sig- Pediatrics, Division of Gastroenterology and Nutrition, nificantly increased jejunal injury score when compared to WT University of Pennsylvania School of Medicine/The Children’s (median 2.5 [range 2-3] and 2.5 [2–3] vs. 1.25 [0–2]). TLR2 and Hospital of Philadelphia. TLR4 deficient mice had significantly elevated TNF-a protein (1287 168 and 1556 326 vs. 48 46 pg/mg TP, mean The function of microRNA in mammalian organogenesis is SEM). After I/R, both B6.TLR2/ and B6.TLR4/ mice virtually unknown, although numerous studies have demon- had significantly lower protein levels of IFN-g (158 68 and strated tissue-specific expression of individual miRNAs. To 110 68 vs. 900 253 pg/mg TP) and IL-17 (139 84 and address the role of miRNA in hepatobiliary development we 157 82 vs. 1232 892 pg/mg TP). have characterized miRNA expression in the embryonic and Conclusion: B6.TLR2/ and B6.TLR4/ mice suffer newborn mouse liver using a microarray comprising probes increased jejunal injury via an altered immune response, which complementary to all known and predicted mouse miRNAs. We includes attenuation of both Th1 and Th17 pathways. We have identified a set of miRNA transcripts with significant propose that the acquisition and recognition of commensal changes in expression during liver differentiation and morpho- bacteria is imperative for normal mucosal immune development genesis, including one miRNA (miR-223) which is expressed in that is protective against I/R injury that approximates NEC. the portal mesenchyme and another (miR-30a-5p) which is These findings support the identification of a probiotic that expressed in the ductal plate adjacent to the portal mesenchyme. would have both TLR2 and TLR4 ligands to prevent NEC. These are the first examples of spatially restricted miRNA expression in the liver. We have used antisense morpholino 79 technology to knock down expression of miR-223 in the larval zebrafish liver. The resulting fish have both abnormal biliary SEMIAUTOMATED QUANTIFICATION OF ENTERIC microanatomy and deficient biliary excretion of the fluorescent BACTERIA IN HISTOLOGY SECTIONS marker PED-6. This represents the first known example of a Matthew Goldman1, Cristina Semino-Mora1, Thomas requirement for a miRNA in biliary development, and it McAvoy2, Armando Sardi3, Carolyn Sullivan1, Andre Dubois1.

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1Uniformed Services University, Bethesda, MD; 2University of PCR products were purified, labeled with Cy5 or Cy3, and Maryland, College Park; 3Mercy Health Services, Baltimore. hybridized to Agilent mouse proximal promoter arrays. To identify developmentally-regulated methylation changes in Background: Determination of the density of H. pylori in liver, two independent P21 vs. E17.5 cohybridizations histology section has been performed using the Sydney system were performed; we focused on genes showing concordant (grading0–3),butthismethod isonlysemiquantitativeandhighly methylation changes in both co-hybridizations. subjective. We have previously developed a point-counting Results: This approach identified 20 candidate genes showing stereological light microscopy method to quantify 16S rRNA two-fold gain of methylation, and 50 candidates showing of H. pylori and other enteric bacteria in specimens from patients 50% reduction of methylation from E17.5 to P21. Validation with Pseudomyxoma peritonei, a disease resulting from perfor- of candidates was performed by quantitative bisulfite sequen- ation of appendiceal carcinoma. However, this method is time cing of hepatic DNA from E17.5 and P21 mice (n = 5/group). In consuming and requires user experience. The goal of this study all six genes examined thus far, the bisulfite sequencing results was to develop a computer-based method to automate and accel- show excellent quantitative agreement with the methylation erate the process while maintaining a high degree of accuracy. changes identified by MSA array (P21:E17.5 ratio): Fcgrt Methods: The program is based on the MATLAB platform and (0.15), Azgp1 (0.19), Phydh1 (0.20), Mcm2 (0.49) Cox4i2 its associated toolboxes and involves an initial training step in a (4.0), and Rorc (4.2). representative slide to classify bacteria and host cells by their Conclusions: The MSA microarray is capable of detecting even color. This segments an image into different regions in the relatively subtle changes in locus-specific CpG methylation. Lab color space. The Lab refers to 3 dimensions in the color space, where the vertical L axis is intensity, and 81 the horizontal a and b axes contain the color information. The resulting classes are fixed and new images are analyzed. THE EFFECT OF THE HEPATITIS B VIRUS X The program identifies bacteria, outlines them, gives the user PROTEIN ON THE INNATE IMMUNE RESPONSE 1 2 1 the option to accept or reject the identified bacteria, and finally Priya Venkataraman , Betty L. Slagle . Pediatric Gastroenter- 2 calculates the relative area of bacteria. ology, Hepatology, and Nutrition, Molecular Virology and Results: With supervised selection, bacteria identified by the Microbiology, Baylor College of Medicine, Houston, TX. program closely corresponded to those visualized by the pathologist (R = 0.976) while providing fast and objective analysis Background: Hepatitis B virus (HBV) causes acute and chronic without requiring special training of the person operating the inflammation of the liver that can vary greatly in severity. system. Similar results were obtained using sections stained by Activation of immunity plays a central role in influencing viral fluorescence and immunohistochemistry. replication and clinical outcome of infection. The early immune Discussion: This software allows for objective determination of response events following HBV infection of hepatocytes are bacterial density while improving efficiency and accuracy and poorly understood. Previous work in chimpanzees suggests that reducing the time involved with manual counting of the slides. It HBV may avoid inducing the innate immune response during the is currently applied to specimens and biopsies to quantify the first weeks of infection, and the mechanism by which this occurs bacterial load of various human and animal tissues. is currently unknown. We hypothesize that HBx, the sole HBV regulatory protein, may provide an immune evasion function. 80 Methods: Transgenic mice expressing HBx under the control of a liver-specific promoter (ATX mice; n = 5) and nontransgenic METHYLATION-SELECTIVE AMPLIFICATION (MSA) wildtype (WT) littermates (n = 6) were injected intraperitoneally MICROARRAY IDENTIFIES GENE-SPECIFIC with 5 ug/g lipopolysaccharide (LPS) as a surrogate inducer of the METHYLATION CHANGES DURING innate immune response and sacrificed at 8-hrs postinjection. POSTNATAL MOUSE LIVER DEVELOPMENT Livers were analyzed for alterations in the host innate immune 1 2 3 Richard Kellermayer , Marie T. Rached , Jean-Pierre Issa , response using a semi-quantitative Western blot to measure the 3 2 1 Lanlan Shen , Robert A. Waterland . Section of Pediatric acute phase reactant protein, serum amyloid A (SAA). Liver 2 Gastroenterology, Hepatology and Nutrition, Departments of histology and ALT levels were analyzed to rule out differential Pediatrics and Molecular and Human Genetics, Baylor College effects of genotype to LPS. Liver tissues were then processed for 3 of Medicine, Houston, TX; Department of Leukemia, M.D. gene expression profiling using Super Array analysis. Anderson Cancer Center, Houston. Results: SAA expression in the LPS-treated ATX livers was diminished to 35% of that measured in the livers of LPS-treated Background: The role of DNA methylation in regulating WT mice (P = 0.02), with no differences in histology or ALT developmentally programmed changes in gene expression levels observed between the 2 groups. In addition, 23 (5.2%) of remains unclear. We therefore wished to determine if the the 440 genes examined by Super Array analysis revealed substantial changes in transcriptional activity between late-fetal significant differential expression between the ATX and WT and weanling liver correlate with gene-specific changes in mice. All 4 cytokine and 4 acute phase response genes tested CpG methylation. were down-regulated in the ATX mice. Materials and Methods: Liver tissue was collected from late Conclusion: These results support the hypothesis that HBx may fetal (E17.5) and weanling (P21) C57BL/6J mice. Hepatic act to diminish the LPS-induced host innate immune response. genomic DNA was digested first with the methylation-sensitive Down-regulating innate immune response pathways may facili- endonuclease SmaI (blunt ends) then with its methylation- tate virus replication and/or allow for establishment of infection insensitive isoschisomer XmaI (sticky ends). Ligation-mediated in the liver.

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82 Background: Wilson disease is a relatively common autosomal recessive disorder. Although many studies have correlated BILE DUCT DEFECTS AND HEPATIC STEATOSIS IN genotype and phenotype, less is known about correlations THE ZEBRAFISH MUTANT DUCT-TRIP between genotype and subclassified hepatic manifestations with Randolph P. Matthews1,2, Kristin Lorent3, Yuehua Huang4, 4 3,5 1 histopathologic evidence. We assessed these relationships in Ian Blair , Michael Pack . Division of GI, Hepatology, Korean WD patients. and Nutrition, The Children’s Hospital of Philadelphia, Methods: Total 183 patients were diagnosed with WD at Asan Philadelphia, PA; 2Department of Pediatrics, 3Department of 4 5 Medical Center from January 1994 to Nov 2006. We retro- Medicine, Department of Pharmacology, Department of Cell spectively analyzed the risk factors associated with liver trans- and Developmental Biology, University of Pennsylvania School plantation, clinically and pathologically subclassified hepatic of Medicine, Philadelphia. manifestation and other phenotypes, and the statistical correlations among genotype, laboratory and liver histopathology Understanding biliary development will greatly facilitate stu- and clinical courses. dies of the pathogenesis of disorders of the neonatal biliary tract Results: 178 patients (97.3%) had hepatic manifestations, such as biliary atresia. We have previously demonstrated that 56 (30.6%) had neurologic, 75 (41.0%) had ophthalmologic the molecular processes that govern biliary development are manifestations, 30 (7.1%) had hemolytic anemia, and 4 (2.2%) well-conserved between mammals and zebrafish. The zebrafish was asymptomatic. The most common mutations in Korean WD mutant duct-trip exhibits degeneration of bile ducts and patients were R778L (36.09%), A874V (9.76%), N1270S hepatocytes during development. The hepatocyte phenotype (5.92%) and L1083F (4.73%). Age at diagnosis was the most is associated with hepatic steatosis and mitochondrial important risk factor for the neurologic manifestation anomalies, and hepatocytes degenerate to a degree that they (P < 0.001), clinically subclassified chronic hepatitis are likely nonfunctional. The causative gene of duct-trip is (P = 0.001) and liver cirrhosis (P = 0.005). R778L homozygotes involved in methionine metabolism, and the mutation results had significantly decreased levels of serum ceruloplasmin in a global inhibition of methylation. Inhibition of DNA meth- (P = 0.026) and were increased risk for neurologic and ophthal- ylation likely results in the bile duct phenotype, while the mologic manifestations. R778L heterozygotes were at decreased hepatocyte phenotype is likely due to several causes related risk for clinically and pathologically subclassified liver cirrhosis to methylation inhibition. Thus, homozygous duct-trip larvae (P = 0.048, 0.043), but increased risk for chronic hepatitis offer an intriguing model of metabolically initiated hepatic (P = 0.041) compared with nonR778L genotype. A874V hetero- failure. Interestingly, heterozygous adult duct-trip zebrafish zygotes had a significantly decreased serum ceruloplasmin exhibit hepatic steatosis without degeneration, and thus may (P < 0.001) but at increased risk for chronic hepatitis serve as a model for fatty liver disease. (P = 0.047) and decreased risk for liver cirrhosis (P = 0.028). Conclusion: Age at diagnosis was the most important risk factor 83 for WD manifestations. R778L heterozygote and A874V genotype were associated with increased likelihood of milder hepatic DEFECTS IN INTRACELLULAR TRAFFICKING IN manifestation. R778L homozygotes had a significantly decreased THE ZEBRAFISH BILE DUCT MUTANT PEKIN 1,2 1,2 1 serum ceruloplasmin, were associated with increased likelihood Randolph P. Matthews , Steven EauClaire . Division of GI, of neurologic and ophthalmologic manifestations compared Hepatology, and Nutrition, The Children’s Hospital of with R778L heterozygotes and the other genotypes. Philadelphia, Philadelphia, PA; 2Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia. Esophagus/Stomach Generation of zebrafish mutants can provide an effective method for identifying genes involved in developmental pro- 85 cesses. We use the zebrafish to study biliary development, a process that at the molecular level is well conserved among A GEOGRAPHIC SPATIAL ANALYSIS OF A LARGE vertebrates. The compound PED6 can be used to assay biliary COHORT OF CHILDREN WITH EOSINOPHILIC function, and we use PED6 as a primary screen for biliary ESOPHAGITIS: IS THERE EVIDENCE FOR ENVIRONMENTAL INFLUENCES? mutants. The mutant pekin demonstrates bile duct defects and 1,4 3 3 skin hypopigmentation, which appear to be related to abnormal James P. Franciosi , Tara Jackson , Marlen Kokaz , Vicky Tam3, Chris A. Liacouras1, Jonathan Spergel2. intracellular trafficking. Genetic characterization of pekin is 1 2 ongoing; it is likely that the defect is in a gene involved in Gastroenterology, Hepatology and Nutrition, Allergy and Immunology, The Children’s Hospital of Philadelphia, intracellular trafficking, similar to the human arthrogryposis/ 3 renal dysfunction/cholestasis syndrome. Philadelphia, PA; School of Social Policy and Practice; 4Clinical Center for Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia. 84 CORRELATION OF GENOTYPE AND PHENOTYPE IN Background and Aims: Previous studies have suggested a KOREAN PATIENTS WITH WILSON DISEASE rising prevalence of eosinophilic esophagitis (EE) in the last ten KeunWook Bae, SunYeon Lee, JooYoung Jang, HanWook Yoo, years. Currently, it is not known whether the rising number of KyungMo Kim. Pediatrics, Asan Medical Center, Seoul, South children diagnosed with EE is due to greater physician aware- Korea. ness of this disorder or due to environmental influences. Clus-

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E33 tering of EE subjects by household location and socioeconomic mine whether the increasing incidence of EE diagnoses is due to context would suggest that environmental risk factors play a the appearance of a new disease or changing endoscopy prac- role in the pathogenesis of EE. In this study, we aim to tices with regard to a greater recognition of EE from GERD. determine whether children with EE are geographically related compared to census data and sub-specialty controls. 87 Methods: Geographic Information Systems (GIS), coupled with spatial analytical tools, offers a framework for conceptualizing, DISSOCIATION BETWEEN SYMPTOMS AND data mapping and analyzing household location and overall HISTOLOGICAL SEVERITY IN PEDIATRIC neighborhood characteristics. EE subject demographics were EOSINOPHILIC ESOPHAGITIS 1 1 2 combined with spatial analysis using GIS technology to develop Scott Pentiuk , Phillip Putnam , Marc Rothenberg . 1 2 a cartographic model of a cohort of children with eosinophilic Gastroenterology, Allergy, Cincinnati Children’s Hospital, esophagitis. A case-control design was used to compare EE Cincinnati, OH. subject demographic information to Philadelphia census data, and two control cohorts of subjects from The Children’s Hospital Background: Eosinophilic esophagitis (EE) is a growing clinical of Philadelphia Gastroenterology and Allergy Clinics. entity. Currently, endoscopic biopsy is the only accepted method Results: A cartographic model using a cohort of 495 children to diagnose EE. No attempts to correlate patient symptoms with eosinophilic esophagitis in the greater Philadelphia area with the presence of EE or as a marker of severity have been will be presented. reported. We created a pediatric EE symptom score (PEESS) and Conclusions: Geographic context and neighborhood character- compared the results with histologic findings in the esophagus. isticsofEEsubjectscomparedtocontrolsmayprovideinsightinto Materials and Methods: Children with histologic diagnosis of environmental factors that contribute to the pathogenesis of EE. EE (and/or their parents) completed a survey prior to endoscopy, rating the frequency and severity of vomiting, nausea, abdominal pain, dysphagia, heartburn, chest pain, regurgitation, 86 food impactions, early satiety, and poor appetite. Possible score ESOPHAGEAL EOSINOPHILIA IN PEDIATRIC ranged from 0–98. Eosinophil number in biopsy specimens PATIENTS UNDERGOING ENDOSCOPY IN 1985 from the esophagus was correlated with PEESS. James P. Franciosi1,4, Clare Li2, Justine Shults4, Mary Leonard4, Results: Forty-nine subjects (age 3–18 years) with histologic Jonathan Spergel2, Chris A. Liacouras1, Eduardo Ruchelli4. EE completed the PEESS. Newly diagnosed, untreated EE 1Gastroenterology, 2Allergy and Immunology, 3Pathology, subjects (N = 15) had a mean score of 24.7 16.4 (range 2– The Children’s Hospital of Philadelphia, Philadelphia, PA; 56.5). The remainder were previously diagnosed (mean time 4Clinical Center for Epidemiology and Biostatistics, University from diagnosis 24.4 23.7 months) and on diet therapy (14/34), of Pennsylvania, Philadelphia. topical steroids (19/34) or oral prednisone (1/34). The mean score for all treated patients was lower than in untreated Background and Aims: Currently there is controversy as to patients: 15.6 12.9 (range 0–47, P = 0.046). The mean score whether the rising number of children diagnosed with eosino- for treated patients in histologic remission was 14.8 11.1 philic esophagitis (EE) is due to greater physician awareness or (range 0–38), which was the same as treated patients with due to a true increase in the number of incident cases. In this active EE [16.7 15.1, (range 0–47)], irrespective of treatment study, we aim to determine the proportion of children with type. Abdominal pain was the most frequent and severe symptom. A weak correlation was found between the PEESS and the possible EE among those with esophageal eosinophilia ident- 2 ified by upper endoscopy with biopsy in 1985 using today’s number of eosinophils in the distal esophagus (r = 0.40). Of 20 diagnostic criteria. treated subjects in histologic remission, 17 (85%) continued to Methods: In 1985, during a 12 month consecutive time interval, report symptoms. Three children with active histologic EE upper endoscopy pathology reports and biopsy slides were (10%) were asymptomatic. reviewed by an experienced pathologist. Conclusions: Children with untreated EE had a higher PEESS Results: 146 non-foreign body upper endoscopies with biopsies than treated subjects. Symptoms persisted in 85% of EE patients were performed, of which 107 (73%) were first time endoscopies. despite histologic resolution, and 10% with active EE report no Of the 107 subjects, the median age was 6 years (range 1 month- symptoms. Our data indicates a marked dissociation between 21 years); 54% were male; 82 (77%) had esophageal biopsies symptoms and histology in pediatric EE. obtained; and 23 (21%) had complete esophageal, stomach and duodenal biopsies performed. Among all endoscopies with eso- 88 phageal biopsies, 24 subjects (29%) had only one esophageal biopsy while 23 subjects (28%) had 3 or more esophageal ENDOSCOPY VERSUS ESOPHAGEAL biopsies. Three of 82 (3.7%) had 15 or more esophageal eosi- EOSINOPHILIA: CAN WE TRUST OUR EYES? 1 2 1 1 nophils while 12 subjects (14.6%) had 1–14 esophageal eosino- Alycia Leiby , Robert Garola , Seema Khan . Pediatric 2 phils in the most densely populated high powered field. Gastroenterology, Pathology, Alfred I. duPont Hospital Conclusions: In 1985, among children undergoing upper endo- for Children, Wilmington, DE. scopy with esophageal biopsy, 3.7% had possible EE based on histology. However, these patients were not treated with PPI Introduction: Furrows and rings are common in patients with therapy, and a minority had three or more esophageal biopsies, eosinophilic esophagitis (EE) on endoscopy (ENDO), but 30% or biopsies of other portions of the upper GI tract. Further EE patients may have a visually normal esophagus. Non-EE investigation of biopsies from other years is needed to deter- patients may have ENDO findings seen in EE.

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Objectives: Evaluate importance of the ENDO appearance of the were 2.2, 36, and 54 months, respectively. Fifteen of the esophagus in predicting esophageal eosinophilia (ESOP EOS). 17 (88%) patients did not clinically improve post-surgery. Methods: ENDO and biopsies (bx) of 481 patients from July Thirteen of the 15 (87%) fundoplications were done without ‘06-Dec ‘06 were reviewed. 152 cases were included and prior endoscopic or allergic evaluation. Predominant allergies formed 2 groups: 5 eos/hpf at any esophageal level (group found were to cow’s milk, egg, soy, and peanut. Skin testing: A), and any gross esophageal abnormalities (ABN) with <5 eos/ 4 pos, 6 neg, and 7 not done. RAST testing: 9 positive, hpf (group B). One pathologist reviewed all the bx. EOSP EOS 5 negative, and 3 not done. Eventual endoscopy revealed was defined as eos/hpf of 5 and EE as >20. histopathologic evidence of esophagus, stomach, duodenum Results: Group A had 67 cases and 64 patients (75% male). or colonic eosinophils in 6 of 12 (50%) patients. Three patients Group B had 85 cases and 83 patients (50% male). 52% in group without mucosal eosinophils were on an avoidance diet or A vs 17.6% in group B had bx at 2 levels. The ABN in group A steroids prior to endoscopy. Post-allergy evaluation interven- vs group B were: edema 22% vs 21%, erythema 12% vs 15%, tions included: 13 dietary avoidance, 8 elemental diet, and white specks 24% vs 10.5% (P < 0.05), nodularity 18% vs 60% 1 systemic corticosteroids. Twelve of the 15 (80%) patients, (P < 0.05), furrows 40% vs 16.5% (P < 0.05), rings 6% vs 0 who had ongoing symptoms post-fundoplication, had reported (P < 0.05). 89% of cases >20 eos/hpf had any ABN vs 43% in improvement post-allergy intervention. 5–20 eos/hpf (P = 0.009). ENDO was normal in 15% of cases Conclusion: EE/EGE and FA may mimic the presentation of with >20 eos/hpf. ENDO ABN as compared with degree of GERD and may improve with dietary modification. Biopsies eosinophilia in group A were: furrows (P < 0.001) with >10, and allergy testing should be considered prior to fundoplication >20, and >30 eos/hpf (OR = 6.8, 95% CI = 1.8–25); white for reflux symptoms to avoid a potentially unnecessary surgical specks with >20 eos/hpf (P = 0.02) and >30 eos/hpf procedure. (P = 0.007, OR = 6, 95% CI = 1.7–20); erythema and edema were not associated with ESOP EOS (P = NS). A furrowed 90 esophagus has a sensitivity = 72%, specificity = 84%, PPV = 50% and NPV = 93%. Basal cell hyperplasia and tall RESPONSE OF PROTON PUMP INHIBITOR THERAPY papillae were in 100% group A cases and 83% and 69% of IN CHILDREN WITH EOSINOPHILLIC ESOPHAGITIS group B (P = 0.03 and P = 0.004). The frequency of eosinophil Dinesh Pashankar, Gilberto Bultron, Cajaiba Mariana, Miguel luminal aggregation, degranulation and abscesses were also Reyes-Mugica. Yale University, New Haven, CT. significantly higher in >20 eos/hpf vs 5–20 eos/hpf. Conclusion: Furrows and white specks are strongly predictive Background: Eosinophilic esophagitis (EE) has been charac- of EE. The absence of furrows reliably excludes EE. A minority terized histologically by infiltration of more than 20 eosinophils of EE patients may have no gross ABN. Edema and erythema (eos) per high power field (hpf) and is usually treated with are not specific to ESOP EOS. Nodularity is found more often in elimination diet, inhaled or oral steroids. A recent study (1) patients without ESOP EOS. The ENDO data may be limited by reported successful results with proton pump inhibitor (PPI) interobserver variability. therapy in 3 patients with EE. We report response of PPI therapy in children with EE. 89 Methods: Retrospective chart review of children treated with PPI therapy for EE. Esophageal biopsies were evaluated again FUNDOPLICATION IN CHILDREN WITH FOOD in all to assess eos counts and location. EE was diagnosed by ALLERGIES AND EE OR EGE histological counts of more than 20 eos per hpf. 1 1 1 Shervin Rabizadeh , Laurie Conklin , Maria Oliva-Hemker , Results: Seven children (mean age 10.2, range 5 to 19 years; 2 1 Robert Wood . Pediatrics, Division of Pediatric GI/Nutrition, 4 boys) were studied. Main presenting complaints included 2 Pediatrics, Division of Allergy & Immunology, Johns Hopkins epigastric pain (3), food impaction/dysphagia (2) and regurgita- University, Baltimore, MD. tion (2). Endoscopic features included white exudates (3), vertical lines (3), furrowing (1). The average eos count was 48 per hpf and Introduction: Fundoplication, a common treatment for GERD, eos were present in aggregates and in superficial location in all. has known associated morbidities. Though symptoms of food Stomach and duodenum were unremarkable. All patients were allergies (FA) and eosinophilic esophagitis (EE) or gastroenter- treated with lansoprazole 30 mg daily although two initially itis (EGE) may mimic GERD, they are not always considered in received ranitidine. The average follow-up on therapy was the workup pre-fundoplication. This study evaluated clinical 8 months (range 1–20). Two children with epigastric pain and outcomes in children presenting to a tertiary center allergy two with food impaction/dysphagia had complete relief of clinic who had received fundoplications. symptoms. Other three children improved significantly, but have Methods: We performed a retrospective review of all patients in occasional epigastric pain and regurgitation. Three patients had the Johns Hopkins Children’s Center Allergy Clinic database repeat endoscopy after an average of 12 months. Endoscopic from 1999 to 2006, searching for key words ‘‘Nissen’’ and appearance improved from initial findings, but was not normal in ‘‘fundoplication.’’ Patients were further selected based on a any patient. Average eos count per hpf improved from 50 to 23 in history or suspicion of FA or EE/EGE. esophageal biopsies in these three children. Results: Seventeen patients (82% male, 58% white) with Conclusions: PPI therapy may lead to symptomatic improve- history of fundoplication and FA were identified. Presenting ment in children having esophagitis with high eosinophilic symptoms: 11 vomiting, 7 poor growth, 6 respiratory, 5 diar- infiltration. The improvement in endoscopic appearance and rhea/bloody stools, and 2 abdominal pain. Average age of histology is partial with PPI therapy. This observation indicates symptom onset, fundoplication, and first allergy clinic visit that peptic esophagitis may mimic EE in presentation, endo-

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E35 scopic and histology findings; or, that a subgroup of patients Conclusions: Children with GI symptoms should have the with EE may respond to PPI therapy. esophagus biopsied even if endoscopically normal in appear- Reference: ance. The presence of esophageal eosinophils is not specific for 1. Ngo P, et al. Am J Gastroenterol 2006; 101:l666–70. the diagnosis of EE and does not distinguish between the diagnosis of GERD and EE. The overlap between GERD, 91 EE, celiac disease and eosinophilic gastroenteritis may suggest a common final pathway of esophageal eosinophil recruitment CORRELATION OF ESOPHAGEAL EOSINOPHILS and activation. TO THE ENDOSCOPIC AND CLINICAL DIAGNOSIS OF EE 92 Rayna Grothe, Yvonne Romero, Savanna Borne, Samantha Levering. Mayo Clinic, Rochester, MN. PREDICTORS OF RESPONSE TO PROTON PUMP INHIBITOR (PPI) THERAPY AMONG PATIENTS Background: The diagnosis of eosinophilic esophagitis (EE) is WITH SEVERE ESOPHAGEAL EOSINOPHILIA dependent upon characteristic endoscopic and clinical findings Jason Dranove, Miriam Davis, Debra Horn, Kevin Kernek, with large numbers of eosinophils (eos) identified on Sandeep Gupta. Pediatric Gastroenterology, Indiana University esophageal biopsy. School of Medicine, Indianapolis. Objective: The aim was to assess if the finding of 15 esophageal eos per high powered field (hpf) correlated with Background: In general, severe esophageal eosinophilia (SEE) the endoscopic and clinical findings of EE. (15 eos/hpf) is considered to represent eosinophilic esopha- Methods: Records from children ages six months to eighteen gitis (EE). Recent reports have described a few patients with years with 15 eos/hpf on esophageal biopsy were retrospec- SEE who have responded histologically to PPI therapy. Clinical tively identified by using the Co-Path database. Recorded were characteristics predictive of histological response to PPI therapy the number of eos/hpf on biopsy, the endoscopic findings— in patients with SEE are not known. either normal or abnormal, and clinical symptoms. The final GI Aims: To determine predictors of histological response to PPI diagnoses post-endoscopy were recorded. Comparisons were therapy in patients with SEE. made between the two groups of patients, those with normal and Methods: We performed a retrospective review of children with those with abnormal endoscopy findings. SEE who were treated with PPI and underwent repeat endo- Results: Patients with abnormal endoscopy had a mean of 43.9 scopy with biopsies. Response to therapy was defined as (SD 29.8) eos/hpf, while patients with normal endoscopy had a <5 eos/hpf on repeat biopsies. Characteristics of responders mean of 27 (SD 15.4) eos/hpf. Although the majority of patients, (R) and non-responders (NR) were analyzed via student t-test 59 (84%) with 15 eos/hpf, had abnormal endoscopic appear- and x2 analysis. ance, 11 (16%) with 15 eos/hpf appeared endoscopically nor- Results: 43 children met inclusion criteria of which 17 were R. mal. None of the patients with 80 eos/hpf was endoscopically Characteristics of R and NR are in Table 1. normal and each of these patients was diagnosed with EE. Pa- Conclusions: Surprisingly, 40% of SEE patients demonstrated tients with normal endoscopic appearance found to have eosi- histological response to PPI therapy. None of the clinical nophils in their biopsy specimen were more commonly diagnosed characteristics evaluated predicted response to PPI therapy; with GERD. However, the clinician suspected an overlap of both response was not dependent on results of pH study. Additional GERD and EE in approximately 30% of patients with endoscopic factors such as seasonal variation of inflammation and placebo abnormalities. Other diagnoses found in both endoscopically effect need consideration. We intend prospective studies to normal and abnormal patients with 15 eos/hpf on esophageal further explore the role of PPI in treatment of SEE as these biopsy included celiac disease and eosinophilic gastroenteritis. could define a phenotypic subset of EE.

Abstract 92 TABLE 1. R (n = 17) NR (n = 26) Total (n = 43) P value

Males 10 (59%) 19 (73%) 29 (67%) NS Mean age (range) years 7.4 (1–16) 8.6 (1–17) 8.1 (1–17) NS Positive allergy testing when performed 20% 31% 28% NS Vertical lines/furrows 10 (59%) 19 (73%) 29 (67%) NS Esophageal erosions 2 (12%) 5 (19%) 7 (16%) NS Hiatal hernia 2 (12%) 2 (8%) 4 (9%) NS Initial mean eos/hpf count 28.6 31 30 NS RI <6% on pH study 7 (50%) 12 (52%) 19 (51%) NS RI >6% on pH study 7 (50%) 11 (48%) 18 (49%) NS Baseline symptom improvement with PPI 17 (100%) 21 (81%) 38 (88%) NS Mean PPI dose (mg/kg/day) 1.06 0.99 1.02 NS Mean PPI duration (mo) 5 4.5 4.7 NS

Test performed on all except 6 subjects.

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93 (USS) to determine whether this quantitative assessment system could describe a specific nature and severity of gastritis in EOSINOPHILIC ESOPHAGITIS: 30 CHILDREN’S children with H. pylori infection as compared to other causes RESPONSE TO SWALLOWED FLUTICASONE of gastritis. Deepak Sobti, Cary M. Qualia, Jay Mathur, Juan F. Villalona, Methods: We enrolled symptomatic children who required Marilyn R. Brown. Pediatric Gastroenterology and Nutrition, diagnostic endoscopy (EGD) and biopsy. Two independent, University of Rochester Medical Center, Rochester, NY. blinded GI pathologists evaluated each biopsy specimen using the USS. H. pylori was diagnosed by histology or a positive Background: Swallowed fluticasone has become well-accepted culture. as a treatment for eosinophilic esophagitis (EE). Despite Results: 85 children were evaluated over a 3 year period. improvement in symptoms while taking topical fluticasone, high Gastritis was found in 45 patients (53%), including 8 (9%) rates of symptom relapse have been shown upon discontinuation with H. pylori infection. The findings are summarized in the of this medication. The purpose of this retrospective review was Table. Significantly more H. pylori infections had a mixed acute to determine the short- and long-term response of children with and chronic cell infiltrate than did other causes of gastritis and EE to swallowed fluticasone. the infections were also significantly more severe. The positive Methods: The charts of 160 children diagnosed with esophagitis predictive value of the combination of mixed cell infiltrate and (ICD-9 code 530.1x) at the University of Rochester between May severe gastritis was 100% in our population. 2003 and June 2006 were reviewed. Sixty of these patients were Conclusions: This limited sample indicates that H. pylori diagnosed with EE by strict histological criteria (20 eosinophils infections in children have a distinctive pattern in regards to per high power field). Charts of 30 patients (age range: 1 to the nature and severity of inflammation as compared to other 18 years, mean 8.62 years) with EE that had undergone at least causes of gastritis. Patient enrollment in the study continues. two esophagogastroduodenoscopies (EGDs) and had been subjected to treatment with swallowed fluticasone were reviewed in greater detail. Sex, age of symptom onset, reported symptoms, Non-Hp gastritis H. pylori specific food allergens, endoscopic findings, number of eosino- N=37 N=8 P value phils per high power field, the type of intervention (medical and/ Mean age (SD), yrs 13.7 (3.1) 11.5 (3.8) NS or dietary), along with the response to the intervention were Acute/chronic nature 5 (14%) 7 (88%) <0.05 recorded. Gastritis severity Results: Twenty three (77%) of the 30 patients were male. The Mild 32 (86%) 0 <0.05 most common reported symptoms were dysphagia (53%) and Moderate 5 (14%) 2 (25%) NS vomiting (50%). Although 29 (97%) of the patients were pre- Severe 0 6 (75%) <0.05 scribed a proton pump inhibitor (PPI), only 9 of 22 (32%) were diagnosed with acid reflux during a 24-hour pH probe study off PPI therapy. While taking swallowed fluticasone, 28 patients 95 (93%) experienced a resolution of clinical symptoms, and EVALUATION OF A SECOND-GENERATION 29 patients (97%) had histological improvement (decreased GI SYMPTOM ASSESSMENT INSTRUMENT number of eosinophils/high power field). Two patients showed TO DETERMINE GASTRITIS AND THE PRESENCE no clinical response to fluticasone. Upon the discontinuation of OF H. PYLORI IN CHILDREN fluticasone, 46% of patients sustained a recurrence of their John D. Snyder1, Ben D. Gold2, Steven Czinn3, Yunn-Yi Chen4, symptoms. Jeannette Guarner5, James M. Perrin6. 1Pediatrics, 4Pathology, Conclusion: The results of this retrospective study suggest that University of California-San Francisco; 2Pediatrics, while most patients with EE will respond to swallowed fluti- 5Pathology, Emory University, Atlanta, GA; 3Pediatrics, casone, many will relapse after stopping the treatment. University of Maryland, Baltimore; 6Pediatrics, Massachusetts General Hospital, Boston. 94 Background: Previous studies have demonstrated a poor cor- EFFECT OF H. PYLORI ON THE NATURE AND relation between abdominal signs and symptoms of pain and H. SEVERITY OF GASTRIC INFLAMMATION IN pylori infection in children. However, these studies were carried CHILDREN out before the development of validated pediatric GI symptom 1 2 3 John D. Snyder , Jeannette Guarner , Yunn-Yi Chen , Ben D. assessment instruments (SAI). We evaluated the ability of a 4 5 1 3 Gold , Steven Czinn . Pediatrics, Pathology, University of second generation SAI to determine the presence of gastritis and 2 4 California-San Francisco; Pathology, Pediatrics, Emory correlation with H. pylori infection. 5 University, Atlanta, GA; Pediatrics, University of Maryland, Methods: We enrolled children who required diagnostic endo- Baltimore. scopy and biopsy for evaluation of their abdominal pain. An SAI (0–5 severity score) was completed by the patient or their Background: Several specific disease states have distinctive parent. Histologic assessment of the biopsy specimens was patterns of gastric inflammation. For example, gastric Crohn made by 2 blinded GI pathologists using the updated Sydney disease typically has a lymphocytic infiltrate and may have non- System. H. pylori was diagnosed by histology or culture. caseating granulomas while allergic disease is delineated by an Results: 88 children were evaluated over a 3-year period. eosinophilic infiltrate. We used the updated Sydney System Gastritis was diagnosed in 43 (49%) of the children, including

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8 (9%) with H. pylori infection. SAI findings are summarized in the table. The severity of chest pain, burping, and regurgitation No Inﬂamm. Gastr. Eso. N=44 N=37 N=7 P value in the H. pylori patients was greater than the other 2 groups and reached statistical significance in several categories. Mean age (SD), yrs 13.1 (3.6) 12.8 (3.8) 12.5 (4.1) NS Conclusions: Our preliminary data indicate that the SAI may be Mean SAI score (SD) useful in distinguishing children with H. pylori infection from Abdominal pain 3.8 (1.0) 3.9 (1.0) 3.4 (0.8) NS Nausea 2.7 (1.7) 2.7 (1.7) 1.4 (1.4) <0.05 those with pain but no inflammation and those with non-H. pylori gastritis. Enrollment in the study is ongoing. Nausea/vomiting 1.2 (1.7) 1.3 (1.6) 0.1 (0.4) <0.07 Vomiting 1.4 (1.8) 1.5 (1.4) 0.3 (0.8) <0.07

No Inﬂamm. Non-Hp H. pylori N=43 gastrits N = 35 N=8 P value 97 Mean age (SD), yrs 13.1 (3.6) 14.5 (2.3) 11.5 (4.5) NS SEROPREVALENCE OF HELICOBACTER PYLORI Mean SAI score (SD) IN 30 CHILDREN AT ORPHANAGE OF ROZO, Abdominal pain 3.7 (1.0) 3.9 (0.7) 3.5 (1.5) NS COLOMBIA Burping 1.7 (1.6) 2.1 (1.4) 3.9 (1.6) <0.01 1,2 1 1 Carlos A. Velasco , Carolina Ochoa . Pediatrics, Universi- Chest pain 1.4 (1.4) 1.9 (1.3) 2.9 (1.9) <0.03 2 dad del Valle, Cali, Colombia; Universidad Libre, Universidad Regurgitation 1.1 (1.4) 1.3 (1.8) 2.3 (2.3) <0.06) Autonoma de Occidente, Cali. Compared to ‘‘H pylori only’’; 2-tailed Student t test. Introduction: Approximately 50% of world population is infected by Helicobacter pylori, which is why it is considered 96 a public health issue. Although most of the diseases associated with this infection are present in middle-aged population, many EVALUATION OF A SECOND-GENERATION GI studies have demonstrated the infection acquisition at early SYMPTOM ASSESSMENT INSTRUMENT TO stages of life and increases prevalence with aging. DETERMINE ESOPHAGITIS IN CHILDREN Objective: To determine the seroprevalence of Helicobacter 1 2 3 4 John D. Snyder , Ben D. Gold , Czinn Steven , Yunn-Yi Chen , pylori infection among 30 children at orphanage of Rozo 5 6 1 4 Guarner Jeannette , James M. Perrin . Pediatrics, Pathology, in Colombia. 2 University of California-San Francisco; Pediatrics, Case Report: Our study consisted of 30 girls, between 6– 5 3 Pathology, Emory University, Atlanta, GA; Pediatrics, 18 years old, orphans, which habit at orphanage of Rozo. 6 University of Maryland, Baltimore; Pediatrics, Massachusetts Identification, height, weight and IgGHp data were collected. General Hospital, Boston. Global undernutrition was defined as weight/age deficit >10%, acute undernutrition as height/age deficit >10% and chronic Background: Studies of abdominal pain in children have undernutrition as weight/height deficit >5%. No nutritional been hindered by the lack of effective symptom assessment difference was found between IgGHp positive (n = 11) and instruments (SAI). As part of an ongoing study, we have IgGHp negative (n = 9) girls (P > 0.05). evaluated the ability of a second generation SAI to distinguish Conclusions: The seroprevalence of Helicobacter pylori infec- patients with histologic evidence of esophagitis from those tion among 30 girls at orphanage of Rozo in Colombia was with histologic gastritis and abdominal pain with no inflam- 36.7%, without nutritional difference among them. Main symp- mation. toms were of gastrointestinal type. Methods: We enrolled children who required diagnostic endoscopy and biopsy for evaluation of abdominal pain. An 98 SAI (0–5 severity score) was completed by each patient and/or their parent. Histologic assessment of the biopsy specimens was A TWO-YEAR EXPERIENCE WITH THE made by 2 blinded GI pathologists. 24-HOUR MULTICHANNEL INTRALUMINAL Results: 88 children were evaluated over a 3-year period. The IMPEDANCE-pHMETRY TO EVALUATE findings are summarized in the table. Symptoms related to GASTROESOPHAGEAL REFLUX combinations of nausea and vomiting were reported less Marina Orsi, Gabriela Donato, Judith Cohen, Laureana Olleta, frequently by patients with esophagitis compared to the other Daniel D. Agostino. Pediatric Gastroenterology Unit, Hospital 2 groups, but only the data related to nausea alone reached Italiano, Buenos Aires, Argentina. statistical significance. The small cohort size to date limits the determination of statistically significant differences in the other Background: The Multichannel Intraluminal Impedance (MII) 2 categories. is a new method to study gastroesophageal reflux, it allows the Conclusions: Our preliminary data indicate that the SAI study of acid/non acid reflux, the height and duration of each may be useful in distinguishing children with histologic episode. It is also capable to differentiate if the descent of pH is esophagitis from those with abdominal pain but no inflam- related to a real event or just to the ingestion of acid beverage mation and from those with histologic gastritis. These or food. findings suggest that a combination of signs and symptoms Aim: To evaluate the number of non acid and acid episodes of may help to identify children with esophagitis. Enrollment GER with the MII-pH in two years period at a different age. To to obtain a sufficiently powered patient population is analyze the behaviour of GER considering bolus clearance and ongoing. the height of the column.

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Abstract 98 Table %Acid Clearance Acid Non-acid Group exposure, N Median bolus (sec), N Median Group episodes, N Median episodes, N Median

I 124 0.80 124 14 I 124 19 124 21 II 119 1.0 119 16 II 119 21 119 11 Mann-Whitney U test (P) 0.057 <0.001 0.543 <0.001

Materials: A prospective study was conducted since January upper endoscopy. To determine the number of acid and 2005 to December 2006. Patients were divided according age non acid episodes, bolus clearance in relation to mucosal in GI<1.91 yr, GII > 1.91 yr. The study was performed during damage. 24 hr with a Sleuth GER Monitoring Recorder catheters with Material and Methods: Since May 2005 to April 2007, 27 chil- 7 impedance sensors plus one pH detector at the distal end. dren (17 boys/10 girls) with 9.5 years median age (r 1–18 yrs) Results: 243 children were evaluated; mean age 3.9 yr SD 4.5, suspected of GER were evaluated. In all of them an upper range 0.04–19, median 1.91(1st-3rd centile) (0.41–7). The endoscopy with biopsies was performed and subsequently a number of total episodes with the pHmetry was increased in 24 hour MII-pH study was performed with a Sleuth Monitoring GI to GII (P = 0.002). The number of NAGER by impedance was Recorder with a ZPN (S61COIE) catheter with 7 impedance significantly increased in GI to GII. No difference was found in sensors and one ph probe at the distal end. The biopsies were the number of acid events instead there is an increased bolus informed by two different pathologists in a blinded manner. clearance with a higher percentage of acid exposure in GII. Bolus Results: No difference was found in number of acid events clearance: Median 15.7 sec 5.3. Younger children showed an detected by pHmetry or by IMM nor in bolus clearance increased number of total GER episodes mainly because of more with IMM. nonacid events. Elder children presented a slower clearance with Conclusions: In this group of patients, esophageal damage a higher acid exposure. No difference was observed in the height seems to have more correlation with non acid exposure. No of the reflux column in either age groups. one method alone was able to detect gastroesophageal reflux Conclusions: The MII-pH is a better method particularly in in all cases. Although histological evaluation of the esopha- infants with more nonacid reflux, not detected by conventional geal mucosa resulted somewhat better since it is an invasive pHmetry. This new method showed that elder children have method and requires sedation or anesthesia; in children, higher acid exposure with worse clearance which may be pHmetry and probably impedance appear as useful first line important for therapeutic management. diagnostic tools.

100 99 A DAMPENED PROINFLAMMATORY ENDOSCOPY AND 24-HOUR MULTICHANNEL CELLUAR IMMUNE RESPONSE IN HELICOBACTER INTRALUMINAL IMPEDANCE FOR PYLORI–INFECTED CHILDREN GASTROESOPHAGEAL REFLUX DIAGNOSIS IN Gayle Horvitz1, Steven Czinn2, Thomas Blanchard2, INFANCY Dexter Thompson1, Kimberly Balark1, April Cameron1, Judith Cohen Sabban, Marina Orsi, Gabriela Donato Bertoldi, Walter Ifeadike1, Mark Rigby1, Eli Rosenberg3, Laureana Olleta, Nancy Mun˜oz, Daniel D. Agostino. Pediatric Benjamin Gold1. 1Pediatrics, 3Biostatistics, Emory University, GastroenterologyUnit,HospitalItaliano,BuenosAires,Argentina. Atlanta, GA; 2Pediatrics, University of Maryland, Baltimore.

Background: Children with gastroesophageal reflux (GER) Background: Helicobacter pylori (Hp) causes gastritis, gas- evaluated with the 24 hr Multichannel Intraluminal Impe- troduodenal ulcers and gastric cancer. The nature of the immune dance-ph (MII-pH) monitoring may present with or without response elicited by Hp contributes to specific disease pheno- esophagitis. It is a matter of debate if it is acid or non-acid types. Different outcomes are observed with Th1/proinflamma- exposure, or time of bolus clearance what generates more tory (eg, IFN-g) vs. Th2/immunoregulatory (eg, IL-4) responses esophageal damage. (ie, pangastritis versus ulcers). The characterization of syste- Aim: To evaluate children with suspected (GER) with the mic immune phenotypes in Hp infected children remains 24hr Multichannel Intraluminal Impedance-pH and with poor.

Abstract 99 Table pHmetry pHmetry Acid episodes Non-acid episodes Bolus clearance positive negative MII positive MII negative (median) (median) (median)

Esophagitis (21/27) 7 14 16 5 26.9 16.8 14 Normal mucosa (6/27) 1 5 2 4 26.8 10.1 12

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Aims: We characterized the systemic inflammatory response to <20 liver biopsies, and 80% performed <5 paracenteses Hp in children and adults; specifically, deciphering a predomi- (NASPGHAN recommendations are 100 colonoscopies, 20 nant Th1 or Th2 response comparing Hp infected vs. uninfected liver biopsies, and 5 paracenteses to achieve competency). children and adults. 75% decided to pursue careers in academic medicine, and Methods: 25 patients (18 children, 7 adults), had Hp deter- 16% in private practice. 68% of trainees participated in some mined (21 Hp- and 4 Hp+); EGD + biopsy (children; histology, type of basic research and 64% in clinical research. 22% of urease test) or 13C urea breath test and serology (adults). fellows hoped to conduct basic science and 74% hoped to Subjects’ peripheral blood mononuclear cells (PBMC) were engage in clinical research as attending physicians. 98% of separated from whole blood using gradient centrifugation. fellows believed their programs had adequately prepared them PBMC proliferation and secretion of 4 cytokines (IL-4, IL-8, to provide appropriate medical care for their patients. The IFN-g, RANTES) were measured after 60 hours of incubation majority thought they were competent or proficient teachers, and exposure to phytohemagluttanin (PHA), Hp whole-cell and rated themselves as advanced beginners or competent when protein (WCP), PHA + WCP, or neither (control). asked to evaluate their research skills. Results: Proliferation: see table. IFN-g secretion was less in Conclusions: Clinical exposure and the opportunity to perform PBMC exposed to Hp WCP compared to PHA (P < 0.01). IL4 procedures are independent of program size. Trainees may not secretion was greater in PBMC stimulated with PHA + Hp WCP be performing sufficient numbers of procedures. The majority compared to PHA alone (P < 0.01). IL-8 and RANTES of fellows will pursue academic careers. responses were variable. Conclusions: Hp WCP dampened the host PBMC proliferative response and IFN-g secretion of mitogen-stimulated PBMC 102 isolated from children. Our data supports the immune evasion SLIDING HIATUS HERNIA AND PEDIATRIC GERD properties of Hp; which might be necessary to facilitate Wikrom W. Karnsakul1, Stacey Gillespie1, Mary Cannon2, persistent colonization in early childhood. Eyassu Hailemichael2. 1Pediatrics, Robert C. Byrd Health Sciences Center, 2Radiology, West Virginia University School Proliferation in Children of Medicine, Morgantown.

Mean Hp+ (n = 3) Hp (n = 15) Background: The relationship between hiatus hernia (HH) and No stimulation 0.41 0.206 0.451 gastroesophageal reflux disease (GERD) has been previously PHA 0.52 0.223 0.579 recognized. The incidence of HH could be under-diagnosed since Hp WCP 0.39 0.224 0.419 its diagnosis requires radiographic or endoscopic examinations. PHA + Hp WCP 0.42 0.224 0.462 Objectives: To identify the frequency of HH in children with Absorbance; P < 0.05 compared to PHA. history of GERD and the significance of HH size. Methods: Outpatient records of children diagnosed with GERD were reviewed from May 2004 to May 2007. GERD was 101 diagnosed based on history, 24 h pH monitoring, upper endoscopy (EGD), and UGI study. Those with food allergy, inflam- PEDIATRIC GASTROENTEROLOGY FELLOWS, matory bowel disease, post-Nissen fundoplication, GI obstruc- CLASS OF 2007: HOW WELL ARE THEY PREPARED tion were excluded. The size of HH is determined by the length FOR THE FUTURE? of HH body above lower esophageal ring (<2 and >2 cm for Cary M. Qualia, Thomas M. Rossi, Marilyn R. Brown. Pediatric small and large HH respectively). Gastroenterology and Nutrition, University of Rochester Results: GERD was diagnosed in 299 children (98% Caucasians, Medical Center, Rochester, NY. mean age 8.04 years; 1 mo-19 y, 146 female, 163 male) at West Virginia University Hospitals. UGI was done in 125 children Background: Pediatric gastroenterology fellows are expected to without evidence of GI obstruction. Sliding HH was detected in acquire skills as clinicians, researchers, and educators. To answer 67 children (mean age 6.8 y, 27 female, 40 male). No difference of whether or not the size of a pediatric gastroenterology training presenting symptoms was noted between GERD children with program affects a fellow’s training and future position choice, to and without HH. A small and large HH were observed in 47 (mean examine training experiences of individual fellows, and to see age 7 y, 18 female, 29 male) and 20 (mean 3.2 y, 9 female, how graduating fellows rate their abilities as clinicians, research- 11 male). 39 underwent EGD. Mild esophagitis was present in ers and teachers, an e-mail survey was conducted. 24 and 9 children with small and large HH, respectively. Erosive Methods: A 52 question survey was e-mailed to 77 third-year esophagitis was observed in 2 children with large HH, one of pediatric gastroenterology fellows. Respondents were stratified which developed iron deficiency anemia. Prolonged combined according to the size of their training program, with small use of prokinetics and acid therapy was required in 20 children programs graduating 1 fellow per year, medium programs (42%) with small HH and 8 children (40%) with large HH. When graduating 2, and large programs graduating 3. medical therapy failed, Nissen fundoplication significantly Results: 50 completed surveys were returned. Clinical exposure improved reflux symptoms in 4 children with large HH and 3 and the opportunity to perform procedures was independent of infants with small HH. program size, with the average fellow spending 10 to 12 months Conclusion: The frequency of HH is high in our series. There on inpatient supervision and 1 half day per week in an outpatient were no differences in demographic characteristics, esophageal setting. The average trainee performed 150–200 upper endos- pathology, requirement of medical or surgical treatment copies and 50–100 colonoscopies. 62% of fellows performed between children with small and large HH.

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103 Methods: Caregivers of children <12 months to 17 years participated in an online consumer Internet survey. Caregivers GASTROESOPHAGEAL REFLUX FREQUENCY IN who completed the survey totaled 847 for infants (I) aged <12 CHILDREN WITH ESOPHAGEAL VARICES months, 1004 for young children (YC) aged 1–4, and 3126 for Maira P. Sa´nchez, Roberto Cervantes, Dante Bacarreza, Ericka older children (OC) aged 5–17. Published (validated) GERD Montijo, Norberto Mata, Jaime Ram´ırez. Gastroenterology and questionnaires were used where applicable (IGERQ-R, GSQ-I, Nutrition, National Institute of Pediatrics, Mexico City, Mexico. and GSQ-YC). Additional questions were developed based on the literature, physician interview, and feedback received during Introduction: Esophageal varices (EV) are present in 80–97% pretesting of the survey. of children with portal hypertension. Studies based in adults Results: Prevalence of GERD varied by age and survey tool suggest that EV can cause motility disorders, esophageal clear- used. GERD was noted in 8.4% and 33.2% of infants when ance as well as lower esophageal sphincter (LES) pressure using the IGERQ-R and GSQ-I. Prevalence in YC was 26.6% alterations, all of which can predispose to GER. The frequency using the GSQ-YC. Gender, caregiver education, household of GER in pediatric population is 8–10%. income, and exposure to smoke were not risk factors in either Objective: To determine the frequency of pathologic GER in group. Hispanic vs white race was a factor only in the YC group children with chronic hepatopathy and/or suspected EV of any (42.2 vs 26.3, P <.05). Respiratory symptoms and eating other cause. problems were more common in both groups. YC with GERD Methods: 50 children participated in this prospective, were more likely to experience hoarse voice, throat clearing, cross-sectional, comparative and observational study. All and constipation. In OC, weekly heartburn and acid regurgita- children were studied in our department from July 2003 to tion was reported in 5 and 7% of participants; 18.3% had 2+ December 2005. All children between 3 m-18 years with symptoms of GERD/week. Black vs white race and Medicaid vs chronic hepatopathy and/or suspected EV were included. Upper PPO health coverage were risk factors for some GERD symp- gastrointestinal endoscopy was performed in all cases to detect toms. OC with >2 symptoms/week were more likely to have EVand children were assigned to groups (Group 1: with chronic cough, congestion, sore throat, eating avoidance, globus, hoarse hepatopathy with EV; Group 2: with chronic hepatopathy with- voice, and throat clearing. out EV). 24-hour pH monitoring was performed in all cases. Conclusions: Symptoms of GER and GERD are common in (Digitrapper pH monitor). Pathologic GER was considered if children and vary by age. Respiratory and eating problems are 2 or more Boyle criteria were met. Patients were excluded from common in all ages of children with GERD and GERD symp- the study if they had neurologic damage, a history of schler- toms. Further studies are needed to develop and assess tools for otherapy and/or EV band ligation, or if they had received either pediatric GERD. H2, proton pump inhibitors or prokinetics. SPSS14 was used for statistical analysis. 105 Results: A total of 50 children completed the study. 30 children had EV (group 1), 17 of which were female, ages 3–160 months DO JEJUNAL FEEDS DECREASE GASTROESOPHA- (median 78.5 m, mean 90 m). 12 of 30 (40%) met Boyle criteria GEAL REFLUX AS DETECTED BY pH-MII? for GER. Group 2 comprised 20 children (10 male), ages 9– Rachel Rosen, Phillip Levine, Samuel Nurko. Children’s 156 months (median 73.5, mean 51.8 m). 5 of 20 (25%) met Hospital Boston, Boston, MA. Boyle criteria for GER. There were no significant differences among both groups (Fischer exact test p0.055). Background: Jejunal feeds (JF) have been used as an alterna- Conclusions: Pathologic GER was more frequent among chil- tive treatment for GERD but no studies have examined their dren group 1(40%). However, there was no statistical difference efficacy in reducing reflux. between both groups. The frequency of pathologic GER in both Aims: 1) To determine reflux profiles during JF, 2) to compare groups was grater than the general population. Prophylactic use reflux profiles between patients with JF, GERD and controls, of H2 or proton pump inhibitors is granted. and 3) to determine if JF reduce GERD-related hospitalizations. Methods: This is a retrospective review of patients who under- 104 went pH-MII testing while receiving JF between 2002 and 2007. We determined the frequency of reflux during jejunal PREVALENCE OF GERD AND GERD SYMPTOMS IN feeds (JF) and non-feed periods (NF). The reflux profiles were CHILDREN: AN INTERNET SURVEY compared with untreated GERD and control patients. 1 2 2 Suzanne P. Nelson , Emily Mulvihill , Kelly Peters , Smita Results: The mean age of 13 patients was 75 62 months. The 3 1 2 Kothari . Northwestern University, Chicago, IL; Mattson Jack mean duration of JF and NF periods was 15.2 4.9 and 3 Group, St. Louis, MO; R&D, TAP Pharmaceutical Products 8.1 5.6 hours, respectively. Reflux profiles are shown in Table Inc., Lake Forest, IL. 1. Comparisons of JF patients with GERD and controls are shown in Table 2. The mean number of GERD-related hospi- Background: Past surveys on the prevalence of pediatric talizations in the year prior to and after J tube placement was GERD symptoms have focused on a narrow demographic 2 1 and 1 1, respectively (P = 0.04). group. New survey instruments that define GERD are available Conclusion: Significantly more reflux events occurred during but have not reported prevalence. JF than NF periods. Even though there were fewer GERD- Objective: This study assessed current prevalence rates of related hospitalizations after the initiation of JF, there were no GERD and GERD symptoms in a diverse demographic popu- differences between the heights and the total numbers of reflux lation of children. events between GERD and JF patients. This suggests that

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GERD complications may be related to other reflux character- TABLE 1. Acid Reflux Indices in Infants with Respiratory istics beyond the number and height of events. Manifestations of GER

TABLE 1. Comparison of Reflux Profiles During Jjejunal Feed Proximal Distal Pearson and Non-feed Intervals Reflux index channel channel correlation Feed interval Non-feed interval P value Total number of 12.9 15.2 23.6 21.1 0.832 reflux episodes No. of acid events 15.2 16.4 3.0 7.6 0.007 Fraction of time 3.4 4.1 6.2 6.4 0.788 No. of non-acid events 17.4 16.5 9.1 17.1 0.2 pH <4 (%) No. of pH-only events 8.6 12.1 1.8 3.6 0.03 No. of long reflux 1.4 2.4 2.3 2.9 0.623 No. of MII events/hr 2.2 1.4 1.1 1.2 0.003 episodes (>5 min) Duration of longest 7.9 9.1 13.0 18.9 0.634 reflux (min) TABLE 2. Comparison of Reflux Profiles Between JF, GERD Esophageal clearance 2.7 1.4 2.7 1.1 0.513 and Vontrol Patients time (min/episode) JF GERD Control P value Correlation is significant at the 0.05 level (2-tailed). Correlation is significant at the 0.01 level (2-tailed). No. of acid events 18.1 21.6 47.4 17.1 26.4 16.8 0.003 No. of non-acid events 26.5 27.4 7.5 5.2 7.4 4.7 0.02 No. of pH-only events 10.5 15.0 26.4 15.2 13.7 12.0 0.04 No. of total MII events 51.4 23.6 54.9 19.9 33.8 19.1 0.07 % full column events 26.5 16.3 30.5 14.8 24.4 19.8 0.72 107 CLINICAL, ENDOSCOPIC, AND PATHOLOGICAL 8 of 13 on PPI. CHARACTERISTICS OF HELICOBACTER PYLORI INFECTION IN A SOUTH TEXAS PEDIATRIC 106 POPULATION Andrea L. Haws3, Dewitt Davenport2, Mihaela Ringheanu1,3. ACID REFLUX IN PROXIMAL ESOPHAGUS IN 1Pediatrics, 2Pathology,Valley Baptist Medical Center, INFANTS WITH RESPIRATORY SYMPTOMS Harlingen, TX; 3University of Texas Health Science Center N. Muckova, A. Shah, S. Rajcevich, Y. Lopez, G. Yanni, at San Antonio. M. Shah. Pediatrics, Loma Linda University, Loma Linda, CA. Aims: To investigate the relationship between H. pylori infec- Introduction: Despite a fairly routine use of continuous dual- tion and the histology of gastroduodenal disease in a sympto- channel esophageal pH monitoring (EpHM) of infants with matic, infected pediatric population. To examine the reliability suspected gastroesophageal reflux (GER), there is little data of the H. pylori antibody titer by ELISA and of the rapid urease available about the utility of proximal channel findings compared test (CLO test). to distal channel findings in patients with different symptoms. Methods: Medical records of all H. pylori infected children Aim: The purpose of this study was to find out whether there is diagnosed in 2003–2007 were reviewed for demographics, a correlation between pH probe reflux indices (RI) in proximal symptom nature and duration, laboratory results, and endo- esophagus (PE) and distal esophagus (DE) in infants with scopic findings. Using the updated Sydney System visual respiratory symptoms (RS) due to suspected GER who under- analog scale, gastric and duodenal biopsies were reviewed by went continuous dual channel EpHM. two independent observers and graded for H. pylori density, Methods: We retrospectively reviewed RI data in infants with mononuclear and polymorphonuclear (PMN) cell number and RS (cough, wheezing and gagging) suspected to be caused by location, atrophy, metaplasia, and presence of lymphoid GER, who were admitted to Loma Linda University Children’s follicles. Data were analyzed for frequencies, and bivariate Hospital and underwent dual channel EpHM between January correlations were done between clinical, endoscopic and path- 1, 2005 and December 31, 2005. EpHM was performed using ology results using SPSS software. Medtronic recorder and pH probes with sensors spaced 5 cm Results: The cohort of 60 children was predominantly His- apart. RI in PE and DE were compared using Pearson Corre- panic, ages 3 to 18 years, 51.7% male. Presenting symptoms lation anlysis. were abdominal pain in 66.7% of cases, emesis/hematemesis in Results: There were 41 infants (age range 2 weeks to 12 months), 11.7%, pyrosis/regurgitation in 11.7%, and anorexia in 3.3%. who underwent EpHM during the study period. The results of our A positive antibody titer was found in 67% of infected patients, analysis are reported in Table 1. Our data of RI in PE and 81% had a positive CLO test. The number of H. pylori in were compared to previously published normal data (Bagucka, the stomach correlated significantly (P < 0.05) with the 2000). positive CLO test, and approached significance with the Conclusion: 1. RI in PE and DE are strongly correlated in ELISA. Strong correlations were found between the number infants with RS and suspected GER. 2. Esophageal clearance of H. pylori in the stomach, the nodular appearance of mucosa time and fraction of time pH < 4 are increased in infants with on endoscopy (P < 0.01), and the number of gastric intrae- RS and GER as compared with previously published RI in pithelial and lamina proprial PMN and mononuclear cells normal children. 3. Further studies are needed to compare RI in (P < 0.01). One subject had intestinal metaplasia, and one PE of patients with different symptoms attributed to GER. had gastric atrophy.

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Conclusions: The degree of infestation with H. pylori is Aim: To describe the effect of gastroesophageal reflux disease strongly correlated with gastric nodularity and with the degree (GERD) on the activities of daily living (ADL) of caregivers for of active and chronic inflammatory changes in the stomach of young children who have GERD. H. pylori infected children. There was no correlation between Methods: An 8-week, multicenter, double-blind, clinical trial symptoms and severity of inflammation. was conducted to evaluate safety and clinical outcomes of esomeprazole treatment for GERD in 1–11-year-old children 108 (D9614C00097). At baseline and final visits, caregivers of 1- to 5-year-old children completed the Pediatric GERD Caregiver IDENTIFICATION OF GENETIC FACTORS FROM Impact Questionnaire (PGCIQ). Responses were scored on a THE HOST AND THE BACTERIA IN CHILDREN 5-point scale (1 = never to 5 = always), with higher scores INFECTED WITH H. PYLORI VERSUS NONINFECTED indicating a more negative impact on ADL. Mean response CHILDREN scores were calculated for each of the 7 domains. Changes from Sergio J. Ferna´ndez, Hugo E. Lagunes, Margarita Camorlinga- baseline domain scores were assessed by 2-sided paired t-tests; Ponce, Armando Madrazo de la Garza, Javier Torres-Lo´pez. no adjustments were made for multiplicity, and no between- Gastroenterology Pediatric Division, Hospital de Pediatr´ıa group comparisons were done. Centro Me´dico Nacional Siglo XXI, IMSS, Mexico City, Mexico. Results: Of the 108 patients randomized, 52 were 1- to 5-year- old patients, and 47 caregivers of these patients completed the Objective: To establish the histologic difference in H. pylori PGCIQ at baseline and final visits. Baseline PGCIQ scores infected children versus non infected children, to evaluate indicated that GERD had a negative effect on the caregivers’ whether the H. pylori strains isolated from infected children have ADL. At final visit, all 7 mean PGCIQ domain scores had the virulence genes associated to severe disease, to know if there decreased. Changes from baseline were statistically significant is any HLA difference between H. pylori infected and non for 5 PGCIQ domains (Table 1); those for the other 2 (daily infected children. activities, partner relationship) were not. Materials and Methods: Weincludedpatientsfrom3to17years Conclusion: In this 8-week safety study of children with of age who underwent upper gastrointestinal endoscopy. Antrum GERD, PGCIQ scores for the caregivers’ of the 1–5-year- biopsies for culture, histology and RNA extraction and venous old children with GERD generally improved after the esome- blood were taken. We determined the presence of the virulence prazole treatment period. genes and alleles vacA, cagA and babA by PCR.HLAII charac- Supported by AstraZeneca LP. terization was done from the DNA extracted of venous blood. H. pylori positive case was a child with any of the diagnostic tests TABLE 1. Mean (SD) PGCIQ Domain Scores and Statistically done (serology, histology and/or culture). Significant Changes From Baseline to Last Visit Results: 21/59 patients were H. pylori+ with a prevalence of 35.6%, 17 by histology, 10 by culture, 9 by culture. We observed PGCIQ domain Baseline Last visit Changes greaterleucocyteinfiltration,activityandlymphoidnoduleswhen Physical health 2.78 (1.17) 2.13 (1.20) 0.64 (0.94) we compared infected children vs noninfected (P = 0.001). No Taking care of child 2.67 (1.05) 2.11 (1.04) 0.56 (0.71) difference was found on pathology between cagA+ and cagA- H. Emotional well-being 2.43 (1.14) 1.80 (1.06) 0.63 (0.85) pylori strains. We characterized 28 HLA DQB1 alleles from 14 Social life 2.27 (1.07) 1.88 (1.14) 0.39 (0.73) patients 0501 and 0301 were the most prevalent alleles in the Family relationship 1.77 (1.01) 1.52 (1.01) 0.26 (0.70) H. pylori positive group but also in the negative group and the 0402 allele was found only in the H. pylori negative group. P < 0.05. Conclusions: The highest grade of histology damage in the gastric antrum biopsies of the H. pylori infected children 110 compared with non infected children remarks the role of the BURDEN OF ILLNESS ON PRIMARY CAREGIVERS OF bacteria as one of the most common causes of gastric inflam- PEDIATRIC PATIENTS WITH GASTROESOPHAGEAL mation. There were no difference in the biopsies of the children REFLUX DISEASE with the H. pylori virulence factors in comparison with dose Roger Luo1, Thirumazhisai Gunasekaran2, Marta Illueca1, Peter who did not have them. No significant difference was found in Barker1, Joseph Crawley1. 1AstraZeneca LP, Wilmington, DE; the expression of the HLA DQB1 alleles between the infected 2Lutheran General Children’s Hospital, Park Ridge, IL. versus noninfected children. The 0402 allele could play a protection role for H. pylori infection. Aim: To evaluate the effects of the burden of illness on the caregivers of young children with gastroesophageal reflux 109 disease (GERD). Methods: Children aged 1–11 years who had endoscopically EFFECT OF GASTROESOPHAGEAL REFLUX proven GERD were enrolled in an 8-week, multicenter, double- DISEASE ON THE ACTIVITIES OF DAILY LIVING blind, clinical trial (D9614C00097) evaluating the safety and OF CAREGIVERS FOR YOUNG CHILDREN clinical outcomes of esomeprazole in treating GERD. At the WITH GASTROESOPHAGEAL REFLUX DISEASE baseline and final visits, a subgroup of the caregivers (those of the AFTER ESOMEPRAZOLE TREATMENT 1–5-year-old children) was asked to complete the Pediatric Joseph Crawley1, Vasundhara Tolia2, Marta Illueca1, GERD Caregiver Impact Questionnaire (PGCIQ), composed Peter Barker1, Roger Luo1. 1AstraZeneca LP, Wilmington, DE; of 25 questions. Reported here are findings from 7 of those 2Wayne State University, Detroit, MI. questions designed to gather baseline data on experiences

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E43 related to obtaining a diagnosis, employment, and household and obesity (OB) were defined according to the published expenses. BMI nomogram (OW: >85% <95th percentile; OB: >95th Results: Of the 52 caregivers of 1- to 5-year old children percentile) (www.cdc.org). randomized, 51 returned evaluable questionnaires at baseline. Results: A total of 745 charts were reviewed. Mean age and More than 50% of children experienced a delay of 3 months Male:Female ratio was 10.5 4.2 years, and 1.1:1.0, respect- from symptom presentation to diagnosis; 78% of children ively. Overall, a total of 495 (66.5%) children were diagnosed visited 2 doctors before receiving a correct diagnosis, 29% with GERD. The difference between OW and OB children visited 3, and 18% visited 4 doctors; and 30% of care- compared to normal weight children is shown in the table givers wished the diagnosis and treatment had been sooner. below. Multiple logistic regression analysis showed that only More than 70% of caregivers reported feeling helpless and fearful the male gender was a risk factor for GERD in children before receiving the GERD diagnosis. Forty percent of working (P < 0.0001, OR = 2.151, 95% CI 1.58–2.94), but not age caregivers had to change their employment status by reducing (P = 0.35), or BMI (P = 0.59). working hours, taking a leave of absence, or quitting jobs because Conclusion: Male gender is an independent risk factor for of the child’s GERD. US caregivers (n = 37) had a mean of GERD in children, but not age or BMI. Whether weight loss $166 per month out-of-pocket expenses to care for their children recommendation in obese or overweight children will improve with GERD, of which $55 was for doctor visits. GERD is yet to be determined. Conclusion: Pediatric GERD presents a substantial burden to children’s caregivers. Nearly one third (29%) of the caregivers 112 reported visiting 3 doctors before receiving a correct diagnosis, including some who visited 4. Increasing awareness CHARACTERISTICS OF FUNCTIONAL among pediatricians and parents could help alleviate this GASTROINTESTINAL DISORDERS IN burden, specifically in children aged 1–5 years with an early CHILDREN WITH CHRONIC ABDOMINAL PAIN GERD diagnosis. Jihyun Uhm, Dongsoon Kim. Pediatrics, Eulji General Supported by AstraZeneca LP. Hospital, Seoul, South Korea.

111 Purpose: The aim of this study was to document the causes of chronic abdominal pain in children referred to a hospital setting IS OBESITY A RISK FACTOR FOR and evaluate the frequency and characteristics of functional GASTROESOPHAGEAL REFLUX DISEASE IN gastrointestinal disorder (FGID) classified by Rome III criteria. CHILDREN? A RETROSPECTIVE ANALYSIS OF Methods: One hundred thirty two patients with chronic 745 PATIENTS FROM A PEDIATRIC abdominal pain were evaluated. Examinations were performed GASTROENTEROLOGY CLINIC IN WEST VIRGINIA in order to find organic causes in some patients when organic Yoram Elitsur, Mary Rewalt, Yulia Dementieva. Pediatrics, disease was suspected. Marshall University, Huntington, WV. Results: Among the 132 patients, 20 patients (15.2%) had organic diseases and 112 patients (84.8%) were diagnosed as Background: Obesity has long been considered as a significant having FGIDs. Functional dyspepsia was the most common risk factor for gastroesophageal reflux disease (GERD) in adults, cause of FGIDs, followed by irritable bowel syndrome. Overlap and weight loss constitutes an important recommendation for of some FGIDs was observed in 7 patients (5.3%). therapy. Although similar approach exists for children, such Conclusion: FGIDs are the main causes of chronic abdominal association has not been fully established. pain in children and functional dyspepsia was the most preva- Aim: To assess the association between obesity and GERD in lent disorder. children who attended the gastroenterology clinic at Marshall University. 113 Materials: Children who underwent upper endoscopy for various medical reasons in our clinic were eligible for the REDUCING MORTALITY AND PREVENTING study. A retrospective chart review of those children was ASPIRATION PNEUMONIA IN CHILDREN performed, and the following data was collected: demographic WITH NEUROLOGICAL IMPAIRMENT WHO data, weight and height measurements, and esophageal HAVE GASTROESOPHAGEAL REFLUX DISEASE histology. The diagnosis of GERD was defined as positive Raj Srivastava1,EarlDowney1, Peter Feola1, Matthew Samore1, histology (any degree of esophagitis). Body mass index Richard Holobkov1, Michael Mundorff2, Brent James2,Peter (BMI) was calculated for each patient. Overweight (OW) Rosenbaum3, Paul Young1, Michael Dean1,MollyO’Gorman1.

Abstract 111 Table No. of male/no. No. of GERD BMI No. of pts. (%) Age (Y, mean) P value of female P value (%) P value

Normal 397 (53) 9.9 188/209 256 (65) OW 164 (22) 11.2 0.0004 90/74 0.105 114 (70) 0.253 OB 185 (25) 11.3 0.0002 106/78 0.022 126 (68) 0.345

Chi-square analysis or Student t-test.

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1University of Utah, Salt Lake City; 2Intermountain Healthcare median and range were calculated and compared to published Inc., Salt Lake City; 3McMaster University, Hamilton, ON, series on AIH in ND children. Canada. Results: Seven patients with AIH and DS were included in this case series. The median age at diagnosis was 10 yrs with a range Objective: Compare time to develop aspiration pneumonia of 3–15 yrs. There were 4 males; 2 Caucasians, 2 African- (AP) and improve survival for children with neurological American, 1 Filipino, 1 Hispanic, and 1 Turkish patient. The impairment (NI) and gastroesophageal reflux disease (GERD) most common presenting symptoms were jaundice, fatigue, and following either a first fundoplication (Fundo) or a first gastro- weight loss. Hepatomegaly was present in 4 patients and 3 had jejunal feeding tube (GJT). splenomegaly. Two had other autoimmune diseases including Methods: Retrospective cohort study of children with NI who type 1 DM, thyroiditis, and alopecia areata. All 7 patients were had either a Fundo or GJT, 01/97-12/05 at a tertiary care both ANA+ and SMA +, but none were anti-LKM1+. The lowest children’s hospital. Primary outcome measures were post-pro- Knodell score was 5 but two patients had a Knodell score of 13. cedure AP-free survival and mortality. Secondary measures were Six patients were initially treated with corticosteroids: 3 with failure of treatment. Multivariable Cox proportional hazards steroids alone and 3 with steroids plus AZA. One was treated with regression models were derived using demographic data, cyclosporine alone initially. Three patients are currently on AZA co-morbid conditions, previous AP, and previous procedures. alone. Two are steroid dependent, one now 5 yrs post diagnosis. To overcome non-random treatment assignment bias, a propen- Three are in remission, one has chronic active hepatitis, one with sity score was developed and used in the final Cox models. portal hypertension and coagulopathy. No patients underwent Results: Of the 366 children with NI and GERD, 43 had a first liver transplant. There were two deaths. Several differences GJT and 323 had a first Fundo; of the cohort, 49 patients (13%) between DS AIH and previously reported series of AIH include died and 55 (15%) developed AP. Median length of follow up younger age at diagnosis, longer steroid dependency, and no was 3.4 years. Children who received a first Fundo had similar reported cases of type 2 AIH. rates of AP [hazards ratio 0.71 (0.21–1.69)] and mortality Conclusions: Type I AIH should be included in autoimmune [hazards ratio 0.49 (0.23–1.03)] post-procedure compared to diseases that are more common in children with DS. Further those who had a first GJT, when adjusting for the propensity study is needed to determine if earlier age at presentation and score. 51 children had (17%) failures among the Fundo group; longer steroid dependency are characteristic of AIH in DS. 23 (7%) underwent a second Fundo and 28 (8%)a subsequent GJT. 32 children had (74%) failures among the GJT group; 115 11 (25%) had a subsequent Fundo while 27 (63%) had tube failure (mean 5.3 GJT replaced per patient). LONG-TERM USE OF METHOTREXATE (MTX) Conclusions: Neither a first Fundo or a first GJT for the AS A STEROID SPARING AGENT (SSA) IN management of GERD in children with NI is clearly superior TYPE I AUTOIMMUNE HEPATITIS (AIH) in preventing the subsequent AP or improving overall survival. Grzegorz W. Telega. Pediatric Gastroenterology and Nutrition, This complex clinical scenario needs to be studied in a Medical College of Wisconsin, Brookfield. prospective, multi-center randomized control trial including quality of life outcomes, to evaluate definitively whether one Background: In children AIH can have aggressive course of these two management options is more beneficial. leading to liver cirrhosis and/or liver failure. Steroids can induce remission in AIH. Long term use of steroids is limited by significant side effects. Medications used as SSA include Hepatobiliary/Transport 6-mercaptopurine (6-MP) and azathioprine (AZA). Lack of effectiveness or unacceptable side effects can limit their use. 114 Fear of hepatic fibrosis hindered use of MTX for AIH. Hypothesis: In selected patients MTX can be used in safe and AUTOIMMINE CHRONIC ACTIVE HEPATITIS (AIH) effective fashion as a SSA in the treatment of type I AIH. IN DOWN SYNDROME (DS) Aims: To present result of the pilot study of long term use of Kim-Doan K. Nguyen, Scott Duong, Farrah Lazare, MTX as SSA in 2 patients with AIH who failed therapy with Maria Triantafyllopoulou, Ian Leibowitz, J. Decker Butzner, AZA/6-MP. Rajeev Nagpal, William R. Treem. Pediatric Gastroenterology Methods: We retrospectively reviewed the charts of 2 patients and the AIH in DS study group, SUNY Downstate Medical with type I AIH who were treated with MTX for at least 5 years. Center, Brooklyn. We recorded: age, gender, ethnicity, signs and symptoms, anthropometric data, laboratory data, bone densitometry and Introduction: Autoimmune diseases such as celiac disease, liver biopsy results (LBx). Study was approved by Children’s thyroiditis, and type I DM are more common in patients with Hospital of Wisconsin institutional review board. DS. However, there are no published series on AIH in children Results: Both patients were females diagnosed with type I AIH with DS. based on positive ANA, SMA antibody and LBx showing chronic Aims: We sought to determine the clinical features of AIH in interface hepatitis with mixed mononuclear lobular infiltrate. children with DS and compare them to those reported in Both patients were jaundiced and cirrhotic at diagnosis. Patient 1 children without DS (ND). was diagnosed with microscopic colitis and JRA. Patient 2 was Methods: After an inquiry on the PEDS GI Board, a ques- diagnosed with celiac disease. Despite of therapeutic levels of tionnaire was sent to interested colleagues. Cases that did not 6-TG and 6-MMP both patients weren’t able to wean steroids. meet characteristics of AIH were eliminated. For certain data, Both had significant side effects of steroids including arrest of

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E45 linear growth and/or bone density z-score <2.0. In both patients Introduction: Giant cell formation is frequently seen among AZA was replaced by MTX 10 mg/m2 subcutaneously. Upon infants undergoing evaluation for neonatal cholestasis. Unlike introduction of MTX both patients were weaned off steroids and adults, a variety of neonatal disorders present with giant cell maintained normal AST and ALT. Linear growth and bone hepatitis. We chose to evaluate infants with neonatal giant cell density normalized. LBx at 1, 2, 5 years after starting MTX hepatitis to characterize their clinical presentation and prog- showed improvement in inflammation and fibrosis scores. nosis. Conclusions: In selected patients MTX can be used safely and Materials and Methods: IRB-approved retrospective review of effectively as a second line SSA in type I AIH. Wider use of clinical and pathologic data for all infants with giant cell MTX in type I AIH should be further studied in controlled, hepatitis identified through the pathology archival system from multicenter trial. 1984–2007. Data collected included demographics, age at biopsy (bx), birth history, clinical history, growth data, labora- 116 tory data and histology data. Student’s t-test was used to compare groups. COMBINED HBV INFECTION AND AUTOIMMUNE Results: A total of 51 infants (69% male), mean age 0.2 years HEPATITIS IN A CHILD—A RARE ASSOCIATION were diagnosed with giant cell hepatitis. 12 (24%) infants were 1 2 1 Narayanan Venkatasubramani , Sara Szabo , Steven Werlin . diagnosed with biliary atresia (EHBA), 3 (6%) infants with 1 2 Pediatrics, Pathology, Medical College of Wisconsin, Alagille’s syndrome, and 5 (10%) infants with hypopituitarism. Milwaukee. Other diagnoses included Echovirus 11/liver failure, Dubin Johnson, Niemann Pick type C, PFIC-2, severe combined The coexistence of HBV infection and autoimmune hepatitis immunodeficiency, TPN cholestasis, and alpha-1-antitrypsin (AIH) is rare. We report a 7 yo girl with vertically transmitted deficiency (PiZZ). 1 child with multiple abnormalities still HBV who developed AIH, and responded to immunosuppression has an undefined genetic disorder with persistent hepatosple- and adefovir. A 3 yo girl, recently adopted from China, was nomegaly. 14 patients required transplant (71% biliary atresia); referred for a positive HBsAg test. She was clinically well. 8 pts have died (62% post-transplant); 25% of patients had Physical examination was normal. She was HBsAb -, HBeAg complete resolution of liver disease by 1 year of age. Birth + and HbeAb-. HBV-DNA titer was 4 107 copies/mL. Her ALT weight was greater for biliary atresia patients (P = 0.027). Age varied between 102–124 IU/mL during the next 3 years. At age 7 at time of bx was earlier for infants with biliary atresia than she was well without signs or symptoms of liver disease. Her hypopituitarism (P = 0.02). Length z-score was greater for growth was normal. Physical examination was normal. Her ALT infants with biliary atresia than infants with hypopituitarism was 650 IU/mL. HBV-DNA was 1.7 107 copies/mL. Her (P = 0.013). bilirubin and coagulation parameters were normal. Serologies Conclusion: Giant cell hepatitis is commonly seen in a variety forhepatitis A, C,D, CMV,and EBV were normal. Ceruloplasmin of neonatal cholestatic liver disorders, including extrahepatic was normal. Pi type was MM. Her ANA and anti-SMA titer were biliary atresia, Alagille’s syndrome and panhypopituitarism. 1/160 and 1/26, respectively. Anti-LKM and anti-mitochondrial Most patients with non-EHBA associated giant cell hepatitis antibodies were normal. Liver biopsy showed interface hepatitis, either did not require liver transplantation or had complete periportal plasma cells infiltrate and focal lobular fibrosis con- resolution of their liver disease. sistent with AIH. Immunostaining for HBV surface antigen showed diffuse cytoplasmic positivity with focal membranous staining; in a pattern consistent with chronic HBV infection. The 118 diagnosis of AIH superimposed onvertically transmitted hepatitis ISHAK VS. METAVIR SCORES IN THE B was made. Transaminases normalized after 1 month of EVALUATION OF HEPATIC BIOPSIES IN prednisone (20 mg/d) treatment. Prednisone was tapered and CHILDREN WITH CHRONIC HEPATITIS azathiopurine (50 mg/d) was given as a steroid sparing agent. Elizabeth Hernandez-Chavez1,3, Maria R. Flores-Marquez2, Because of concerns for activation of hepatitis B, adefovir 10 mg Alfredo Larrosa-Haro1,3. 1Gastroenerology and Nutrition, once a day was given. Within 1 month the DNA viral load 2Pathology Deparment, IMSS Hospital de Pediatria, decreased to <100 copies/mL. One year later, transaminases Guadalajara, Mexico; 3Human Nutrition Institute, are normal and HBV-DNA is not measurable. All through the University of Guadalajara, Guadalajara. course, the patient remained symptom-free. In a patient with stablevertically transmitted HBV who develops increasing serum Background: transaminases, a search for other etiologies is critical in choosing Liver biopsy is the gold standard for the the appropriate therapy. Combined immunosuppression and anti- evaluation inflammation and fibrosis in chronic hepatitis viral therapy were successful in normalizing the serum transam- (CH). Ishak score is widely used but it manages a high number inases and suppressing HBV replication. or variables. METAVIR score is simplest but it has been used mainly in hepatitis C; the experience with this score in children 117 with CH is scanty. The aim of our study was to correlate Ishak and METAVIR scores in liver biopsies of children with CHARACTERIZATION OF INFANTS WITH GIANT CH. CELL HEPATITIS Methods: Design: Case-report series. Period: 2000 to 2004. Michael Torbenson1, Carmen Cuffari2, A. O. Scheimann2. Protocol: Liver biopsies from patients with CH were examined 1Pathology, 2Pediatrics, Johns Hopkins School of Medicine, for necro-inflammatory activity and fibrosis with the Ishak and Baltimore, MD. METAVIR scores. Statistics: Pearson correlation.

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Results: n = 21. Median age 8 4.9 years. 12 girls and 9 boys. 120 Cryptogenic HC n = 9, autoinmune HC n = 8, hepatitis C n = 4. For necro-inflammatory activity r = 0.887 (r2 0.78), P < 0.001. HIGH SPONTANEOUS SEROCONVERSION IN For fibrosis r = 0.880 (r2 0.77), P < 0.001. E-ANTIGEN POSITIVE SOUTH ASIAN Conclusions: In our view, a statistically significant association CHILDREN WITH CHRONIC HEPATITIS strength > 0.8 may be considered as a clinically significant B—A CONTRARIAN EXPERIENCE finding. This means that METAVIR score may become S. Venkatesh Karthik, Sanjay Rajwal, Patricia McClean, simplest alternative tool to evaluate liver biopsies of children Suzanne Davison. Children’s Liver and GI Unit, St. James’s with CH. A higher sample size is required to validate these University Hospital, Leeds, UK. findings. Background: The natural history of chronic hepatitis B (HBV) 119 in children depends upon the mode of infection and varies in different regions of the world. Factors influencing natural SUCCESSFUL RECRUITMENT AND seroconversion rates include the route of acquisition and ethni- RETENTION STRATEGIES IN PEDIATRIC city. HEPATITIS C CLINICAL TRIAL Aims: We aim to evaluate the natural history of e-Antigen Aparna Roy1, W. Lieb4, B. Garrett2, M. Hodik3, B. Barton2, positive HBV carriers,including spontaneous seroconversion P. Robuck5. 1Johns Hopkins Medical Institutions, Baltimore, rates, followed-up at a single centre serving an ethnically MD; 2Maryland Medical Research Institute, Baltimore; diverse population. 3University of Florida, Gainesville; 4UCSF, San Francisco; Methods: 47 children (23 males) including 26 Asian, 13 Chinese, 5NIDDK, Bethesda, MD. 7 Caucasian and 5 Black African patients with a median age at diagnosis of 5.5 years (range: 0.6–15.8) were included in the Rationale: Recruitment and retention (R&R) of children with study, of which 36 were infected perinatally. Hepatomegaly chronic hepatitis C virus (CHC) infection in clinical trials was noted in 4 and abdominal pain in one. 2 had clinical present multiple challenges. Effective participant R&R is a splenomegaly. 19 (40%) had elevated ALT (median-101 IU/L; 2 9 large component of study workload and is essential in conduct range: 54–547). HBV DNA levels ranged from 2 10 2 10 8 of clinical trials. Despite R&R’s integral role in randomized (median- 1.8 10 ) in 32 children in whom it was assayed. Three clinical trials, successful strategies are understudied in underwent liver biopsy, all showing variable degrees of fibrosis. children. 3 of 47 completed antiviral treatment (IFN-2, Lamivudine-1), and Objective: To focus on methodological considerations of became e-antibody positive. 2 are currently under treatment. R&R of children with CHC in a complex pediatric clinical Of the remaining 42, 7(17%) have spontaneously seroconverted trial. to e-antibody positive after a median interval from diagnosis of Methods: Data from PEDS-C, a multicenter double blind 23 months (range:1–108). Natural seroconversion rates were placebo controlled randomized clinical trial to determine the 6 out of 21 (29%) in Asians, 1 of 5 (20%) in caucasians. No safety and efficacy of peg interferon alfa-2a (PEG-2a) with other child seroconverted. 5 out of 36 (14%) children with ribavirin (RV) and PEG-2a alone for the treatment of CHC perinatal infection seroconverted. was used. Conclusion: In our heterogenous population, the overall Results: 114 children were randomized. 2 children withdrew seroconversion rate was 17%. Unlike previous studies, both prior to enrollment and 13 withdrew during the course of the Asian and Caucasian children had similar seroconversion rates. study. 2 had serious adverse events of hyperglycemia and Spontaneous seroconversion rates in Asian children at 29%, suicide gesture. Common adverse events were flu-like were much higher than found in previous studies. This empha- symptoms (88%), GI symptoms (59%) and headache sises the necessity of having an adequate control group in (54%). The overall retention rate was 89%. Recruitment all antiviral treatment studies, especially in multicultural strategies included educating families, clinical and research populations. staff; physician referrals; radio shows; information booth and poster in national conferences; PEDS-C study website; 121 registration of the study on NIH website, www.clinicaltrials. gov, and establishment of an exemptions committee. These THE INFLUENCE OF NUTRIENT INTAKE AND mechanisms were complemented by regular follow-up by the BODY COMPOSITION ON BONE MINERALIZATION data coordinating center to help retention. Other determinants IN ADULTS AFTER PEDIATRIC LIVER were scheduling flexibility, home visits, transportation help, TRANSPLANTATION 1,3 2,3 1,3 establishing relationships with families and motivation of Sugianawaty Mulia , Susan Raatz , Khalid Khan . 1 2 3 parents. Department of Pediatrics, Medicine, Nutrition, University of Conclusions: Strategies designed to address R&R in our Minnesota, Minneapolis. large, multicenter, complex pharmacotherapy trial in children with CHC infection were effective in meeting our goals. As a Background: Liver transplantation (LT) is a widespread treat- result we maintained a high retention rate of 89% in spite ment for chronic liver disease and results in increasing risk of of the high incidence of adverse events. Lessons learned fractures due to rapid bone loss. There are few reports of the from our trial will be valuable in designing future pediatric relationship between reported diet, body composition and bone trials. density after pediatric LT. Our objective was to compare

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E47 reported nutrient intake, lean mass (LM) and fat mass (FM) abnormalities were found in esophagus (12 pts: vertical lines from dual-energy X-ray absorptiometry (DXA) of lumbar spine 12, white specks 4, ulcer/erosion 2) stomach (11 pts: erythema bone mineral density (LS-BMD), total body bone mineral 11, nodularity 3, erosion/ulcer 6), duodenum (6 pts: erythema 5, density (T-BMD) and total body bone mineral content nodularity 5, ulcer/erosion 4), colon (4 pts: erythema 4, (T-BMC) in post LT individuals. ulcer/erosion 2). 10/16 (63%) pts had endoscopic abnormalities Methods: In a cross sectional study, we evaluated individuals at multiple sites. Eosinophilic inflammation on biopsy was transplanted as children more than 1 year prior. found in the esophagus (14 pts: severe 9, moderate 1, mild Results: Ten subjects were included (4 m and 6 f). Mean age 4), stomach (11 pts: severe 5, moderate 3, mild 3), duodenum was 22 years (5.1). The mean time post LT was 11.4 years (9 pts: severe 1, moderate 5, mild 3), and colon (7 pts: severe 2, (4.8). Bone-related nutrients were not significantly correlated moderate 3, mild 2). EGI was found at multiple sites in 12/16 with bone mineral indices. FM was not significantly related to (75%) pts. Treatment included switch from tacrolimus to bone mineral indices. No statistically significant correlation cyclosporine (6),switch from tacrolimus to sirolimus (1),switch was observed between body composition and LS-BMD. LM from cyclosporine to tacrolimus (2), swallowed fluticasone (4), showed a strong correlation with T-BMD (r = 0.66, P < 0.05) montelukast (2), gastrochrom (1), prednisone (2), dietary and T-BMC (r = 0.77, P < 0.01). change (2). 12/16 (75%) pts improved symptomatically. Conclusions: In long term, LM influences bone mineral indices Conclusion: EGI was seen in 52% (16/31) of PLTR and was after pediatric LT. The effect of LM was stronger in women than often severe. Esophagus and stomach were most frequently in men, and was stronger on T-BMC than on T-BMD. involved both endoscopically and histologically. EGI should be considered in all PLTR with GI symptoms. Treatment options Correlations of Bone-Related Nutrient Intake and Body should be studied further. Composition to Bone Mineral Indices (r)

Lumbar BMD Total BMD Total BMC 123

Energy 0.07 0.32 0.31 ADVERSE OUTCOMES OF PEDIATRIC Protein 0.05 0.29 0.30 LIVER TRANSPLANT RECIPIENTS TRANSITIONED Calcium 0.23 0.09 0.21 TO ADULT CARE Vitamin D 0.05 0.17 0.29 Rebecca Berquist, William Berquist, Kenneth Cox, Fat mass (all) 0.60 0.34 0.39 Marcia Castillo, Iris Litt. Pediatric Liver Transplant, Female 0.74 0.64 0.73 Stanford University, Palo Alto, CA. Male 0.56 0.33 0.49 Lean mass (all) 0.26 0.66 0.77 Female 0.86 0.90 0.97 Aim: To evaluate the process and outcomes of pediatric liver Male 0.82 0.85 0.96 transplant patients transitioned to adult care at our facility. Methods: We conducted a retrospective chart review of P < 0.05; P < 0.001. 24 patients post-liver transplantation who had transitioned to adult care at our facility by May of 2007. Non-adherence was 122 defined as patient admission to not taking the immunosuppressive(s). CLINICAL, ENDOSCOPIC, AND HISTOLOGIC Results: Of 24 patients, the average age at transition was FINDINGS OF EOSINOPHILIC GASTROINTESTINAL 21.3 years (SD 2.4) with a range of 17 to 27 years. 9 patients INFLAMMATION IN PEDIATRIC LIVER (38%) were autonomous at transition and all were female; TRANSPLANT RECIPIENTS female gender was significantly associated with autonomy at Girish Subbarao, Meltem Zeytinoglu, Sandeep Gupta, Kevin transition by the Fisher exact test (P < 0.0223, 95% CI 0.278– Kernek, Joseph Tector, Jean Molleston. Indiana University, 0.770). 15 patients (65%) were non-adherent pre-transition and Indianapolis. 14 patients were non-adherent post-transition. 3 patients had improved adherence and 2 patients became non-adherent post- Background: Pediatric liver transplant recipients (PLTR) have transition; transition was not significantly associated with an increased predisposition to develop eosinophilic gastrointes- improvement or worsening of adherence. 5 patients (22%) tinal tract inflammation (EGI). There is paucity of information had biopsy-proven rejection and 2 patients had sub-clinical regarding clinical, endoscopic, and histological findings. rejection post-transition; non-adherence was significantly Aim: To study EGI in PLTR. associated with rejection post-transition (P < 0.0189, 95% CI Method: A retrospective analysis of 31 consecutive PLTR who 0.230–0.770). 6 patients (26%) were re-listed for transplan- underwent esophagogastroduodenoscopy (EGD) or colono- tation and 3 patients were re-transplanted post-transition; scopy from 2000–2006. 3 patients were re-listed and 1 re-transplanted secondary to Results: 16 patients (pts) (median age 8.6 [1–18.5] years, chronic rejection. 3 patients died post-transition, 2 secondary to male 7) had EGI. Median age at transplant was 1.5 (0.14– chronic rejection and 1 for disease recurrence. 17.8) years. The underlying diagnoses were biliary atresia (14), Conclusions: Significant adverse outcomes occurred in a alpha-1 antitrypsin deficiency (1), idiopathic cirrhosis (1). majority of patients transitioned to adult care. Non-adherence Immunosuppression was tacrolimus (11), cyclosporine (5), also represented a problem in a large proportion of patients, prednisone (7). Presenting symptoms were abdominal pain many of whom experienced an episode of rejection post-tran- (9), diarrhea (6), vomiting (5), failure to thrive (4), anemia sition. These data suggest the need to develop an interventional (4). 16 pts had EGD and 9 had colonoscopy. Endoscopic strategy to address adherence and the process of transition in a

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E48 prospective manner to improve the outcomes in our transplant 125 patients. IMPACT OF SEROLOGICAL SCREENING ON THE CLINICAL PRESENTATION OF CHILDHOOD CELIAC DISEASE Intestine/Colon/IBD Kelly E. McGowan, Derek A. Castiglione, J.D. Butzner. Department of Pediatrics, University of Calgary, Calgary, AB, 124 Canada. HLA DQ2 HOMOZYGOTES ARE ASSOCIATED WITH A 24-FOLD INCREASED RISK OF EMA POSITIVITY IN Aim: The impact of IgA-endomysial antibody (EMA) screen- A LARGE SAMPLE OF SERA (N = 1021) ing on the diagnosis of childhood celiac disease was evaluated FROM PEDIATRIC PATIENTS AT RISK FOR in southern Alberta. CELIAC DISEASE IN THE US Methods: Children diagnosed with celiac disease before the Michelle Pietzak1, Tim Schofield2, Matthew McGinniss2. introduction of EMA screening, 1990–1996 (pre-screening 1Pediatric Gastroenterology, University of Southern California group), were compared to those diagnosed after the introduction Keck School of Medicine, Los Angeles; 2Prometheus of EMA screening, 2000–2006 (screening group). Laboratories, San Diego, CA. Results: In the pre-screening group (n = 36), the median age at diagnosis was 2 years compared with 9 years in the screening Aim: To determine the prevalence of Class II HLA DQ2/DQ8 group (n = 199, P < 0.001), while the female to male ratio (1.6:1) haplotypes in a large US pediatric population at-risk for was similar in each group. The incidence of celiac disease tripled celiac disease (CD), and to assess relative risk for CD as from 2.0/100,000 to 7.3/100,000 (P < 0.03) after the advent of defined by endomysial IgA (EMA) positivity and haplotype screening. The proportion of cases presenting with classic group. celiac disease was significantly reduced in the screening group Methods: Blood samples from 1021 pediatric patients at-risk (39/199, 20%) compared to the pre-screening group (24/36, 67%, for CD were analyzed at a commercial laboratory for EMA and P < 0.001), while the incidence remained unchanged (P > 0.05). HLA. High-resolution sequence-specific oligonucleotide probe In the screening group, classic celiac disease remained common typing of CD-associated HLA DQ haplotypes was performed on (67%) in young children (<3 yrs), while ‘‘atypical’’ presentations whole blood DNA. PCR amplification was performed with were most frequently observed in older children and adolescents. biotinylated primers in two multiplex reactions for the In the screening group, 12 new clinical presentations were DQA1 and DQB1 loci. The amplified product was hybridized observed in 84 (42%) children. These included positive family with 35 DQA1 and 37 DQB1-specific probes, and reactivity history (35), isolated abdominal pain (18), endoscopy for other patterns were interpreted with LiRAS software (Innogenetics reasons (8), short stature (6), trisomy-21 (5), constipation (5) and NV; Gent, Belgium) to determine the alleles present. others (7). The clinical presentations of ‘‘abdominal pain Results: Risk for CD, as assessed by EMA+, and stratified by with other symptoms or associated conditions’’ (P = 0.6), type DQ genotype, is summarized in the table. The rate of EMA+ in I diabetes (P = 0.7) and failure to thrive without diarrhea (P =0.4) DQ2 homozygous samples was about 24 times-and in DQ2 occurred with similar frequencies in both groups. In the screening heterozygous samples about 7 times-the estimated prevalence group, 191/199 (96%) children underwent serological screening of 1% for CD in the US. Those who did not carry DQ2 or DQ8 and five (2.5%) true false negatives were observed in IgA had no risk. The EMA+ rate in samples from patients <3 years sufficient children. Three (1.5%) children were IgA deficient. old was 1.9% (3/155). Conclusion: The addition of EMA screening to aid in the Conclusion: These data suggest that testing for HLA DQ2 and diagnosis of celiac disease increased the incidence and age DQ8 haplotypes can effectively stratify pediatric patients into at diagnosis. With EMA screening additional presentations of clinically meaningful risk groups. HLA testing may stratify childhood celiac disease were recognized. pediatric patients at risk for CD who have not yet been exposed to gluten, who are already on a gluten-free diet, or who have 126 indeterminate serology or biopsies. INFLUENCE OF CELIAC ANTIBODIES UPON METABOLIC STATE AT PEDIATRIC EMA+, DIABETES DIAGNOSIS DQ genotype N (%) Alleles detected N (%) Muralidhar Jatla1, Amanda Rewers2, Caroline Kieserman-Shmokler1, Marianne Buzby2, Kathryn Murphy2, DQ2 Homozygous 66 (6.5) DQ2.5 + DQ2.5 or DQ2.2 16 (24.2) 2 1 1 DQ8 Homozygous 7 (0.7) DQ8 + DQ8 1 (14.3) Steve Willi , Ritu Verma . Gastroenterology and Nutrition, 2 DQ2/DQ8 55 (5.4) DQ2.5 or DQ2.2 + DQ8 7 (12.7) Division of Endocrinology/Diabetes, The Children’s Hospital DQ2 heterozygous 341 (33.4) DQ2.5 or DQ2.2 + 25 (7.3) of Philadelphia, Philadelphia, PA. not DQ8 DQ8 heterozygous 164 (16.0) DQ8 + not DQ2 or DQ8 6 (3.7) Background: Celiac (CD) disease is reported to present in DQ2-, DQ8- 388 (38.0) Not DQ2 or DQ8 + not 0 (0.0) DQ2 or DQ8 approximately 5% of children with type 1 diabetes (T1D), most often after T1D has been diagnosed. Both diseases share a DQ2.5 = HLA-DQA105-DQB102; DQ2.2 = HLA-DQA10201- common pathogenesis, result in the production of autoanti- DQB102; DQ8 = HLA-DQA103-DQB1. bodies (AAB) and have significant nutritional implications. Our

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E49 aim was to examine the prevalence of TTG AAB in measures analysis reporting least squares means SE, with newly diagnosed T1D children and explore the relationship alpha = 0.0012. between TTG positivity and the metabolic and immunologic Results: Compared to TG- children, those on RD showed lower manifestations of TID. TSF z score and trend toward increased n telopeptides (Table). Design: All children newly diagnosed with T1D at CHOP There were no differences between TG+ children on GFD or between 7/05 and 9/06 had AAB to various islet cell antigens regular diet. (insulin, glutamic acid decarboxylase{GAD}, islet cell antigen Conclusions: In children with T1D, TG+ status while continuing 512{ICA512}), CD IgA antibodies (tissue transglutaminase on gluten for 1 year was not associated with adverse outcome. {TTG}, endomysial antibody {EMA}), bicarbonate, pH, and Longer follow-up and larger studies are needed to determine the HbA1c performed. optimal timing of, and adherence to, GFD in asymptomatic Results: In total, 191 children were diagnosed with T1D during children with T1D. this period; 23 (12.04%) had TTG+ (20 units). Only 10/23 pts had EMA+. No significant differences were seen in age at 12-month Data on TG- and TG+ T1D Children on Gluten diagnosis, HbA1c or presence of T1D AAB between TTG+ and TTG groups, while bicarbonate was lower in the TTG+ group. TG (n = 64) TG+ (n = 34) P value Conclusion: We found a higher than expected rate of CD AAB positivity in our T1D children, suggesting greater sensitivity in Age (y) 11.4 0.4 11.9 0.6 0.42 Sex (%M) 44 58 0.27 our TTG AAB measurements. CD AAB positivity was associ- T1D duration (y) 4.1 3.1 3.9 2.7 0.73 ated with a greater degree of metabolic acidosis at time of Ln HbA1c 2.1 0.02 2.1 0.03 0.58 presentation. Further analysis may reveal whether nutritional or Ln insulin dose/kg/d 0.2 0.1 0.3 0.8 0.15 immunologic factors mitigate this finding. Body mass index z 0.7 0.1 0.4 0.2 0.16 Tricep skin fold z 1.2 0.1 0.6 0.2 0.003 Lumbar spine Z for bone age 0.5 0.2 0.6 0.3 0.65 TTG positive n = 23 TTG negative n = 168 P value Volumetric lumbar spine Z 0.2 0.3 0.0 0.4 0.80 Urine n telopeptide (% normal 109 12 147 17 0.07 Age (yrs) 9.8 4.0 9.5 4.6 0.67 values for gender and age HbA1c 11.2 1.8 10.8 1.9 0.25 adjusted for bone age) Insulin Ab+ 65.2% 55.9% 0.39 GAD Ab+ 82.6% 79.2% 0.69 ICA512 Ab+ 69.6% 72.1% 0.81 Bicarbonate 16.4 7.6 20.1 6.5 0.03 128 Serum pH 7.28 0.13 7.33 0.12 0.09 OBESITY IN PEDIATRIC CELIAC DISEASE Data on BMI, height percentile, and thyroid hormone levels will be Narayanan Venkatasubramani, Gregorz Telega, Steven Werlin. presented at poster publication. Pediatrics, Medical College of Wisconsin, Milwaukee.

Background: Celiac disease is typically diagnosed in children with failure to thrive and malabsorption or after screening high 127 risk groups such as diabetes. Almost half of adult celiac patients have a BMI >25% at diagnosis. Classic symptoms like diarrhea IMPACT OF CELIAC AUTOIMMUNITY IN DIABETIC are less common in obese patients. Few children have been CHILDREN: 12 MONTH FOLLOW-UP reported with celiac disease and obesity. Since many children 1 2,3 Edward Hoffenberg , Jill Hickman , Georgeanna J. with newly diagnosed celiac disease are identified by screening 2 2 2 Klingensmith , Kim McFann , Lisa M. Emery , high risk groups, obesity is more common than previously 2 2 2 Marian Rewers , Iman Taki , Sharon Vanyi . suspected. 1 2 Pediatrics, UCDHSC and TCH, Denver, CO; Barbara Aims: To estimate the prevalence of obesity at diagnosis in Davis Center for Childhood Diabetes, UCDHSC, Aurora, children with celiac disease and to describe the clinical charac- 3 CO; Pediatrics, Vanderbilt University, Nashville, TN. teristics of this group. Methods: We reviewed the charts of 143 patients with celiac Background: Children with Type 1 diabetes mellitus (T1D) are disease diagnosed between 1986 and 2003 at Children’s at increased risk for celiac disease (CD). Routine screening of Hospital of Wisconsin. Data collected included age, gender, T1D children is based on the concern that asymptomatic CD ethnicity, signs and symptoms, BMI, celiac antibody titers, might adversely impact long-term health outcomes related to small bowel biopsy results and follow up weight 2 years after TID. However, the benefit screening remains unclear. diagnosis. Objective: To determine the natural history of asymptomatic Results: 8/143 (6%) patients with celiac disease had CD, and assess the benefit of GFD in children with T1D and BMI > 95%ile. The mean age was 11.3 years (range 9.5– asymptomatic CD. 12.5) for obese patients vs. 8.3 (range 1–17) years in all celiac Design/Methods: TG children (64) were matched with patients. There was no significant gender difference between tissue transglutaminase antibody positive (TG+) asymptomatic the two groups with a female to male ratio of 5:3 (obese) and children for gender, age, and T1D duration. TG+ children self- 93:50 (non-obese). The most common presenting symptoms selected to gluten free (GFD+, 45) or regular gluten containing among obese patients were abdominal pain (62%), diabetes (RD, 34) diet. Subjects were followed every 3 months with (25%), and diarrhea (12%). 5/5 patients tested for TTG were repeat DEXA after 12 months. We used a mixed model repeated positive, 3/3 positive for EMA, 1/1 positive for anti-gliadin

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E50 antibody. One patient had negative EMA and TTG but positive high tissue transglutaminase (tTG) levels have normal small for HLA DQ2. In this patient the diagnosis was based on biopsy bowel histology: disallowing a diagnosis of celiac disease. But and clinical improvement on gluten free diet. All patients had low disaccharidase levels with normal histology might indicate abnormal biopsies consistent with celiac disease. Lactase early bowel dysfunction. deficiency was present in 37% of patients. Symptoms improved Methods: Biopsy results were examined for all children in all patients on a gluten free diet. BMI decreased in 4 (50%), referred to a gastroenterology clinic, and who had an endo- increased in 2 (25%) and not available in 2 at 2 years after scopy, 2001–2006. Inclusion criteria: eating gluten prior to starting on gluten free diet. endoscopy; tests for tissue transglutaminase (tTG) or endome- Conclusions: 1. Obesity is more common in children with sial antibody (EMA) and gliadin antibodies. All symptomatic celiac disease than previously recognized. 2. In the appropriate children with high tTG levels were offered a gluten-free diet, clinical setting, celiac disease must be considered even in obese whatever the histology appearance. children. Patients: 194 children: 98 males and 96 females; mean age 5.3 years, sd 3.8. They were placed in four groups: 26 (13.5%) 129 ‘‘Definite-celiac’’ disease (histology: villus atrophy); 38 (20%) ‘‘Possible-celiac’’ disease (elevated tTG/EMA but normal small PREVALENCE OF CELIAC DISEASE AND bowel histology; 125 (64%) ‘‘Not-celiac’’ (normal histology CELIAC AUTOIMMUNITY IN CHILEAN CHILDREN and no elevation of tTG or EMA); 5 (2.5%) with ‘‘Congenital AND ADOLESCENTS WITH TYPE 1 DIABETES Sucrase-Isomaltase Deficiency’’ (CSID) (normal histology, MELLITUS normal tTG/EMA, and normal lactase levels). Most ‘‘definite- 1,2 2 1,2 Pamela Jofre´ , Marcela Gonzalez , Ilse Gonzalez , Cristina celiacs’’ had depressed disaccharidase levels. ‘‘Possible-celiacs’’ 2 2 2 1 Semler , Itziar Mondragon , Marta Arriaza . Pediatr´ıa, and ‘‘not-celiacs’’ had lesser degrees of disaccharidase depres- 2 Universidad de Valpara´ıso, Vinã del Mar, Chile; Hospital sion. In ‘‘possible-celiacs’’, maltase depression was associated Gustavo Fricke, Vinã del Mar, Chile. with high tTG levels (x2 =4.6,P < 0.5). Low sucrase was associated with the possibility of celiac disease (x2 =35.6, df =2, Background: The prevalence of celiac disease (CD) in children P < 0.01). On a gluten-free diet, all ‘‘definite-celiacs’’ and with type 1 diabetes mellitus (DM) is significantly higher than 68% ‘‘possible-celiacs’’ improved. Gluten-free response was in the nondiabetic population. Most patients with DM and not associated with maltase levels. associated CD do not develop typical gastrointestinal symptoms Conclusions: Disaccharidase depression was found in most of CD. There is no available data about prevalence of CD either celiacs and over half of children with high tTG but with normal in the general population or in DM patients in Chile. histology. There was an association between high tTG and low Objective: To evaluate the seroprevalence of celiac disease in maltase levels. Disaccharide depression was not predictive of children and adolescents with type 1 diabetes mellitus, the response to a gluten-free diet. follow up of this and prevalence of CD in this group. Methods: In the period 2006–2007, 66 type 1 diabetic patients aged from 3 to 16 years were enrolled in this prospective study. Definite-celiac Possible-celiac Not-celiac CSID IgA transglutaminase was measured by ELISA method. Biopsy n=26 n=38 n = 125 n=5 was performed in persistently seropositive or symptomatic Low maltase 23 (88%) 25 (64%) 74 (59%) 5 (100%) patients. Low sucrase 18 (69%) 9 (23%) 18 (14%) 5 (100%) Results: IgA transglutaminasewas positive in 8 patients (12,1%), Low lactase 14 (54%) 10 (26%) 15 (12%) 0 (0%) 3 of them turned negative during follow-up (37,5% seroconversion).Three out of 4 biopsies were diagnostic for CD. The prevalence of CD was 4,5% in this group. Clinically relevant 131 features in patients with CD were: One patient with ataxia, one IMPLEMENTATION OF A GLUTEN-FREE with overweigh and short stature and one with obesity. DIET RESOLVED THE CHRONIC DIARRHEA Conclusion: Serological markers of celiac disease seem to be AND THE HISTOLOGICAL DAMAGE DETECTED frequent in diabetic patients. Nevertheless, diagnosis must be IN A NONHUMAN PRIMATE MODEL OF GLUTEN confirmed by histological studies which allow us to know the ENTEROPATHY real prevalence of celiac disease in them. The prevalence of CD D. Kryszak1, H. McGill2, M. Leland2, A. Fasano1. 1Pediatrics, in Chilean children and adolescents with DM seems to be the University of Maryland, Baltimore; 2Southwest Foundation for same than in other countries. Seroconversion may be important Biomedical Research, San Antonio, TX. during the follow up. Background: Given the undisputable role of gluten in causing 130 inflammation and immune-mediated tissue damage in celiac disease (CD), this disease could provide unique opportunities DISACCHARIDASE LEVELS IN GLUTEN-SENSITIVE totacklethepathogenicbasisofautoimmuneprocesses.However, ENTEROPATHY the lack of a CD animal model represents a major limitation. We Rodney P. Ford. Children’s Gastroenterology Clinic, have recently described a pedigreed colony of baboons with Christchurch, New Zealand. hereditary chronic diarrheapossibly related to gluten enteropathy. Aims: To establish the effect of the implementation of a gluten- Aim: To assess the value of disaccharidase measurements in the free diet (GFD) on the chronic diarrhea and small intestinal diagnosis of gluten-sensitive enteropathy. Many children with histological damage detected in these baboons.

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Methods: Serum and biopsies samples of affected animals were Conclusions: The possibility of CD remains in a small fraction of analyzed to determine if the diarrhea experienced by these patients who undergo colectomy for medically-refractory UC. A baboons could be secondary to gluten induced enteropathy. lower BMI and a higher anti-ompC titer may be predictive of CD. A subgroup of baboons admitted with hereditary chronic diarrhea were placed on a GFD and monitored for 6 months. Blood samples and duodenal biopsies were collected at base- CD (n = 6) UC (n = 22) P value line, at 3 months, at the conclusion of the study. 2 2 BMI (mean) 16 kg/m 22 kg/m 0.01 Results: Three baboons affected by chronic diarrhea and Anti-OmpC (mean) 16.9 EU/ml 6.2 EU/ml <0.00001 showing elevated serum levels of anti-tissue transglutamiane antibodies (TTG) and/or zonulin levels were enrolled. The intestinal biopsy obtained at baseline showed increased intraepithelial lymphocytes and/or patchy villous blunting with crypt 133 hyperplasia. Following the implementation of a GFD, the three baboons experienced resolution of the chronic diarrhea and a 10% PEDIATRIC INFLAMMATORY BOWEL DISEASE IN weight gain. Within three months, the intestinal mucosal damage SAUDI ARABIA: IS IT INCREASING? resolved and serum zonulin returned within normal levels, while Sahar S. Khorsheed, Anne M. Griffiths. Pediatrics, Military serum TTG remained elevated in one baboon. Hospital, Jeddah, Saudi Arabia. Conclusions: These preliminary observations suggest that a gluten-dependent enteropathy is present in the pedigreed Background and Aim: Chronic Inflammatory Bowel Disease baboon colony studied. The clinical, serological, and histologi- (IBD) is thought to be rare in the Arab countries. We aimed to cal features suggest a similarity to human CD. Therefore, the review the published data on Pediatric Crohn’s Disease (CD) progeny of these sires can be potentially used as a primate and Ulcerative Colitis (UC) in Saudi Arabia (SA). nonhuman model of CD. Material and Methods: Midline search through Ovid and PubMed search engines for all the published articles in SA. In addition, databases for two other local journals (the Saudi 132 Journal of Gastroenterology and the Annals of Saudi Medicine) and the National Meetings and Conferences registry were HOW OFTEN DOES THE DIAGNOSIS CHANGE reviewed manually. FROM ULCERATIVE COLITIS TO CROHN Results: 37 documents were identified and six of them were DISEASE FOLLOWING COLECTOMY IN relevant. Toonisi carried out the first systematic study of IBD in MEDICALLY REFRACTORY PEDIATRIC COLITIS? children in 1993 when he described 17 children with CD. Their Elisa Evers, Marian Pfefferkorn, Steven Steiner. Indiana ages ranged from 5–15 years. The average duration of symp- University School of Medicine, Riley Hospital for Children, toms prior to presentation was 25 months. All patients received Indianapolis. steroid therapy, 64% had attained a remission within 6 months, and 58% required laporotomy. In 1999, a retrospective medical Background: Crohn disease (CD) has occasionally been diag- records review identified 15 children with IBD in central nosed following colectomy for ulcerative colitis (UC). province of SA. Follow up documentation from the same Aims: To determine the frequency of CD in pediatric patients center identified 50 children with IBD between 1993 and who underwent colectomy for medically-refractory UC, and to 2002. The estimated incidence of IBD in central province identify possible predictive factors leading to CD diagnosis. was 0.5/100,000 populations/year with 16% of patients were Methods: The Riley Children’s Hospital database was searched below 12 years of age. Patterns of presentation were UC 48%, for the ICD-9 code for total colectomy. CD 38%, and indeterminate colitis 14%. Results: We identified 212 patients who had a colectomy Discussion: The reviewed articles suggest an increasing inci- between October 1996 and December 2006, 37 of whom were dence of pediatric IBD in SA. This could not be explained only diagnosed preoperatively with UC. The mean age at diagnosis by increasing awareness, but more likely a true increment of UC was 10.7 years (1.3–16.6 years) and the mean age at time noticed with the change of lifestyle of many Saudi children of colectomy was 13.6 years (2–18.3 years). IBD serology was and adolescents. available in 29 patients, and 25/29 (86%) were pANCA- Conclusion: There is evidence of an increasing incidence of positive. IBD serology was negative in 3 and equivocal in 1. pediatric IBD in SA. The new generations of Saudi Pediatric Ten (27%) had nonspecific inflammation of the upper digestive Gastroenterologists are faced with multiple challenges includ- tract, including one each with H. pylori and Giardia lamblia. ing the large geographic area and the rapidly expanding popu- Radiologic studies obtained in 25 (68%) patients indicated no lation with peak expansion in children and adolescence age abnormalities in the small intestine. Prior to colectomy, patients groups. (n = 35) were treated with: corticosteroid (97%), 5-ASA (69%), immunomodulator (66%), infliximab (29%), and cyclosporin 134 (11%). The mean postoperative follow-up was 2.6 years (0–6.5 years). Six patients (16%) were found to have CD at 13 to TREATMENT OF DISTAL RECTAL STRICTURES IN 78 months postoperatively. All 6 patients were p-ANCA CROHN’S DISEASE: DIGITAL DILATATION AND AT- positive prior to colectomy and also had elevated anti-ompC HOME DILATATION, AND LONG-TERM FOLLOW-UP (n = 4), ASCA IgA (n = 2), and ASCA IgG (n = 1). All 6 had T. Gunasekaran. 1Pediatrics, Lutheran General Children’s pancolitis with rectal sparing in one. The table shows the factors Hospital, Park Ridge, IL; 2Pediatrics, Loyola Medical Center, that were significantly different between the 2 groups. Maywood, IL.

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Introduction: 5–6% of Crohn’s patients have strictures of determined by detailed food recall questionnaire and reported colon and nearly half of them are rectal strictures. Surgery vitamin supplements for 18 IBD and 29 controls. Values are for these strictures has risks because of its location. We present mean SD. four patients with distal rectal strictures secondary to Crohn’s Results: RBCF levels were 735 192 ng/ml in IBD and disease, treated with digital or Hegar’s dialtion followed by 590 151 ng/ml in controls (P < 0.001). Total folate intake regular at-home dilation and long-term followup of four. was similar between the groups (339 146 mg/d for IBD Method: Four patients ages 12–18 yrs rectal strictures in the and 386 134 mg/d in controls); all were within the RDI distal rectum secondary to Crohn’s. Prior treatment included (200–400 mg/d) adjusted for age and gender. Mean ratio of folate mesalamine, 6MP and/or infliximab. The strictures were diag- intake to RBCF was 0.50 in IBD and 0.73 in controls (P = 0.025). nosed by digital examination of the anorectum or during Mean Hct was 33.9 4.7% in IBD and 37.5 3.6% in controls colonoscopy. The strictures were dilated under deep sedation (P < 0.001). Whole blood folate levels remained different bet- with the index finger of the examiner (soft stictures) or with ween the two groups: 245.8 56.1 ng/ml in IBD and 218.9 Hegar’s dilators (firm strictures) and was a colonoscopy was 50.2 ng/ml in controls (P = 0.037). completed following the dilation. Patient (or with parent’s help) Conclusions: Our data document increased folate levels in continued dilatation at-home daily as described earlier. Follow newly diagnosed untreated IBD patients compared with healthy up was done up to 3 years. subjects, independent of lower folate intake and lower Hct Results: All patients tolerated the procedure well. One patient among patients compared with controls. The influence of after 2 years improved and stopped dilating (soft stricture), IBD therapy on folate metabolism and clinical implications 2 patients are on daily dilation (one soft stricture and one firm of higher RBC and whole blood folate at diagnosis of IBD needs stricture) and one patient had restenosis which required repeat to be explored. dilation under sedation followed by maintenance at- home dilation. All patients showed normal growth in height and weight. 136 Three patients felt that the procedure substantially improved their life styles and can comfortably pass a bowel movement. Medical INCREASED DOSING REQUIREMENTS OF 6-MP AND treatment for Crohn’s disease was continued. AZATHIOPRINE FOR YOUNGER INFLAMMATORY Conclusion: Digital or Hegar dilatation of distal rectal BOWEL DISEASE PATIENTS strictures is a safe method of treatment. At-home dilatation Andrew B. Grossman, Angela J. Noble, Robert N. Baldassano. by patients or parents is a safe mode of treatment for preventing Division of GI/Nutrition, The Children’s Hospital of Philadel- the recurrence of distal rectal strictures. Soft strictures may have phia, Philadelphia, PA. a better outcome compared to firm strictures. Further studies in a larger group of patients with longer follow up period are Introduction: 6-mercaptopurine (6-MP) and its pro-drug required to determine the safety and efficacy of this mode of azathioprine (AZA) are effective for maintenance of remission management of rectal strictures in Crohn’s disease patients. and reduction in corticosteroid exposure in pediatric inflammatory bowel disease (IBD). The standard dose of AZA is 2.0– 135 2.5 mg/kg/d. The concentration of 6-thioguanines (6-TG), an active metabolite of 6-MP, has been shown to correlate with RED BLOOD CELL FOLATE (RBCF) LEVELS IN therapeutic efficacy. Our aim was to determine whether IBD PEDIATRIC PATIENTS WITH INFLAMMATORY patients 6 years old and younger require higher doses of BOWEL DISEASE (IBD) 6-MP/AZA to achieve therapeutic 6-TG levels and clinical 1 3 1 Melvin B. Heyman , Paul Harmatz , Elizabeth Garnett , remission. 6 7 Harland S. Winter , Robert N. Baldassano , Stanley A. Methods: Retrospective chart review of all IBD patients six 4,5 5 8 Cohen , Benjamin D. Gold , Barbara S. Kirschner , George years old and younger treated with 6-MP/AZA since 2001. Data 9 3 2 1 D. Ferry , Erin Stege , Nina Holland . Pediatrics, University of was recorded for visits 0, 3, 6, and 12 months post initiation of 2 California, San Francisco; School of Public Health, University 6-MP/AZA and additional visits with 6-TG measurements. The 3 of California, Berkeley; Children’s Hospital and Research mg/kg dose of 6-MP was multiplied by 2.08 to establish an 4 Center, Oakland, CA; Children’s Center for Digestive Health- equivalent AZA dose. An abbreviated Pediatric Crohn Disease 5 care, Atlanta, GA; Pediatrics, Emory University School of Activity Index (aPCDAI) was approximated for each visit. 6 Medicine, Atlanta; Pediatrics, Massachusetts General Hospi- Fisher exact test was used for group comparisons and gener- 7 tal for Children, Boston; Pediatrics, Children’s Hospital of alized estimating equations to model correlated outcomes 8 Philadelphia, Philadelphia, PA; University of Chicago Comer (STATA 9.0). 9 Children’s Hospital, Chicago, IL; Texas Children’s Hospital, Results: 26 patients were included in this analysis; 52% had Baylor College of Medicine, Houston. Crohn Disease, 38% indeterminate colitis, and 10% ulcerative colitis. The median age at diagnosis was 3.3 yrs [2.3–4.7 yrs]. Background: Folate is postulated to protect against cell injury The median final AZA-equivalent dose was 3.1 mg/kg/d [2.5– and long-term risk for cancer in IBD. Folate levels are poorly 3.5; max. dose 5.2]. More patients in the AZA >3.0 mg/kg group delineated in children with IBD. as compared to AZA <3.0 mg/kg group achieved an aPCDAI<10 Methods: RBCF levels were determined in 71 children; (P = 0.03) with median follow-up 9.8 months [range 1– 31 patients with newly diagnosed untreated IBD patients 31 months]. The risk of active or steroid dependent disease (19 Crohn’s disease [CD], 9 ulcerative colitis [UC], 3 indetermi- was on average 86% lower if AZA-equivalent was >3.0 mg/kg nate colitis [IC]), mean age 13.3 2.6 (range 6.6–17.5) yrs, and 61% lower per 1 mg/kg dose increase. The correlation and 40 healthy controls, 11.9 3.1 (6.8–17.6) yrs. Intake was between 6-TG and AZA-equivalent dose was 0.35. There were

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E53 two cases of leukopenia and one case of hepatitis in the AZA Background: Probiotics are a commensal bacteria recom- >3.0 mg group and one case of hepatitis in the AZA mended for children with acute diarrhea. The recommended <3.0 mg group. therapeutic dose ranged between 1 109 to 1 1011 CFU/gram Conclusions: 1. IBD patients six years old and younger may per day. The probiotic concentrations in commercial yogurt in need higher than standard doses of 6-MP/AZA. 2. AZA- the US is unknown. equivalent doses of >3.0 mg/kg/d were well tolerated. Aim: To investigate the quantities of live Lactobacillus casei [25th–75th percentile]. (Lc) and Bifidobacterium bifidum (Bb) species in commercial yogurts sold in the US. 137 Methods: Ten different commercial yogurts were investigated. Commercial lactobacillus sample served as control. Yogurt UNCOMMON GROUND—THE MARKED VARIATION samples were cultured on Lactobacillus selective MRS media. IN HOW ENTERAL NUTRITION IS ADMINISTERED IN Colonies were counted and Gram stained. Specific PCR primers CANADA AND THE US were used to determine Lc and Bb species in the yogurts. M. Stewart, A. Otley. Pediatrics, Division of Gastroenterology, Results: All yogurt samples contained live bacteria but the total Dalhousie University, Halifax, NS, Canada. amount was less than 109 CFU/g (Table 1). Gram stain was positive in all colonies. PCR analysis showed the presence of Lc Background: Practice guidelines do not exist for exclusive in 4/9 yogurts and Bb was identified in all yogurts. enteral nutrition (EEN) as primary therapy in pediatric Crohn’s Conclusion: The concentration of live bacteria in commercial disease (CD). To advance the EEN field, and address issues of yogurts meets the National Yogurt Association standard variation in practice, it is first necessary to document what form (1 108 CFU/gram), but did not meet the recommended thera- this variation takes in how this therapy is delivered. peutic concentration for acute diarrhea in children. Common Aim: To describe the practice pattern and infrastructure used to yogurts contain unknown types, and unspecified concentrations administer EEN by NASPGHAN members. of bacteria. The data suggest that commercial yogurts do not meet Methods: Canadian and US members of NASPGHAN were the therapeutic level needed for children with acute diarrhea. surveyed for use of EEN. This study examined responses obtained from regular or sparse users of EEN. Probiotic Concentrations in Commercial Yogurts Results: There was a 31.5% (356/1129) response rate for the survey as a whole, with 67% reporting some use of EEN. Brand Conc. (108 CFU/g) Gram stain Greater than 75% used EEN for ileocolonic disease, isolated upper gut disease, or upper and lower gut disease but rarely Control 77 1.0 + considered it for perianal disease (80%) or colonic disease Dan Active 3.4 1.3 + Yoplait 2.8 1.8 + (67%). There was no clear preference for the type of formula Great Value 3.3 2.4 + used and many physicians report using more than one type; 47% Yobaby 0.5 1.8 + used polymeric, 55% semi-elemental and 47% elemental Breyers-prob 5.2 1.5 + formula. 66% report using in-hospital teaching and initiation Kroger Fr 9.5 6.0 + of EEN. Prevalence of programs to cover costs of formula, Kroger blend 1.3 0.7 + infusion pumps/equipment greater in Canada than US Dannon Fr 2.3 0.5 + (P < 0.001). Dieticians were always involved more often by Dannon Activa 5.0 1.4 + Canadian (92%) than US physicians (44%) (P < 0.05). 71% Breyers Fr 7.0 1.6 + report nasogastric/gastric tube feeding (NG/GT) as their usual route of administration. Canadians more likely to use NG/GT feeds than US physicians (OR 19.87; CI 2.81–399.28). An 139 initial duration of EEN of less then 6 weeks was recommended in 30%, 6–8 wks (46%), >8 wks (25%). Concomitant medical PREDICTORS OF ABNORMAL COLONOSCOPY IN CHILDREN therapy use more common by US compared to Canadian 1,2 1 2 2 1 physicians (63% vs. 24%, p<0.001). Concomitant medications A. Mun˜iz Crim , E. Israel , R. Sege , N. Terrin , A. Casserly , A. Chaglassian2, I. Wilson2. 1Pediatric Gastroenterology and used include: 5-ASA (69%), 6MP/azathioprine (60%), steroids 2 (51%), infliximab (40%) and methotrexate (13%). Nutrition, Massachusetts General Hospital, Boston; Institute Conclusions: This study has shown that in addition to variation for Clinical Research and Health Policy Studies, Tufts-New in frequency of EEN use between physicians, there is also England Medical Center, Boston, MA. significant heterogeneity in how EEN is administered, with differences noted being marked between Canadian and US Background: Colonoscopy is increasingly used as a diagnostic physicians. tool in children. Recent studies have demonstrated up to 40% of colonoscopies in children are normal, yet there are limited data 138 available to guide appropriate patient selection for this procedure. PROBIOTICS IN COMMERCIAL YOGURTS IN THE Objectives: To develop a predictive score to optimize patient US: A REALITY CHECK! selection for colonoscopy. Brian Dunlap1, Vonya Eisinger2, Hongwei Yu2, Yoram Elitsur1. Methods: We studied a retrospective cohort of 791 pediatric 1Pediatrics, 2Microbiology, Marshall University, Huntington, patients who underwent colonoscopy at 2 hospitals in Massachu- WV. setts between 2001 and 2006. These patients were divided into a

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E54 derivation cohort (529 patients) and a validation cohort subtotal villous atrophy), whereas conventional endoscopy was (262 patients). The main outcome measure was abnormal colo- able to detect duodenal abnormalities only when total villous noscopy defined by both abnormal histological findings and the atrophy was present (once), but unable to detect abnormalities final clinical diagnosis. We developed logistic regression models with subtotal villous atrophy (twice). to examine clinical symptoms and laboratory values as predictors Conclusion: ME and NBI endoscopic techniques are available of abnormal colonoscopy and to develop a predictive score. for use in pediatrics and may provide improved endoscopic Results: Mean age (SD) was 12.2 (3.8) and 44% had an abnormal evaluation in children compared to conventional endoscopy. colonoscopy. Erythrocyte sedimentation rate >20 mm (OR: 2.9, The role of ME and NBI in pediatric endoscopy needs further 95% CI: 1.2–2.7), albumin < 3.5 g/dl (10.6, 3.4–32.7), diarrhea evaluation. (1.8, 1.2–2.7), hematochezia (2.7, 1.7–4.2), guaiac positive stool (1.9, 1.2–3.1), family history of polyps (4.2, 2.0–9.0), and weight 141 loss (2.1, 1.3–3.4) were independent predictors of abnormal colonoscopy. For the model including these variables, the area PROCEDURAL LEARNING IN SIMULATED under the receiver-operating characteristic curve (AUC) was 0.79 COLONOSCOPY 1 1 1 in the development population and 0.70 in the validation popu- Rebecca Dezube , Catherine Dale , Matthew Weinger , 2 3 3 4 lation. A 15-point predictive score was developed using beta Roberta Muldoon , Dan Ayers , Sheryl Zhong , Caroline Cao . 1 2 coefficients from the final model. The AUC for the predictive Center for Perioperative Research in Quality, Division of 3 score was 0.76 in the development population and 0.70 in the Colorectal Surgery, Department of Biostatistics, Vanderbilt 4 validation population. We were unable to identify a group with a University School of Medicine, Nashville, TN; Dept of predicted risk of < 10% (low risk) for abnormal colonoscopy. Mechanical Engineering, Tufts University, Boston, MA. Conclusions: We identified several important factors associated with abnormal colonoscopy in children. We were unable to Background: Endoscopy simulator training may improve identify a low-risk population to target for reduction of colono- clinicians’ performance during patient procedures. Little data scopy utilization. exist on how to implement procedural simulators in training curricula. In other domains, directed feedback through coaching 140 improves learning. Objectives: To study how coaching affects medical students’ NEW TECHNIQUES IN PEDIATRIC ENDOSCOPY: learning of colonoscopy using the GI Mentor, a computer-based MAGNIFICATION ENDOSCOPY AND NARROW BAND simulator, and to compare students’ performance with experi- IMAGING enced endoscopists. 1 1 2 1 Peter Ngo , Alex F. Flores , Moises Guelrud . Pediatric GI, Methods: 18 na¨ıve Vanderbilt medical students completed 2 Floating Hospital for Children, Boston, MA; Gastroenterology, 20 hours of colonoscopy training on the GI Mentor. Nine of Tufts-New England Medical Center, Boston. 18 students were randomly assigned to receive coaching. Sub- jects sequentially practiced 10 scenarios. Six experienced Background: Recent technological advances have produced endoscopists completed 6 of the same scenarios in a proscribed videoendoscopes with narrow band imaging (NBI) and mag- sequence over 2 hours. For each scenario, simulator software nification endoscopy (ME). NBI is an imaging technique in calculated performance metrics. Generalized linear mixed which optical filters allow passage of specific narrowed spectral models analysis of variance was used to compare individual components of light (e.g. blue, green) to improve contrast with trainees’ performances over time and between groups as well as blood vessels and improve visualization of the mucosal surface trainees vs. experienced participants. compared to white-light endoscopy. Studies using ME and NBI Results: Intragroup variation was substantial. There were no in adult populations have reported improved identification of significant differences between uncoached and coached groups’ specialized intestinal metaplasia in Barrett’s esophagus and peak performances or in time required to reach proficiency. villous atrophy in celiac disease. To the author’s knowledge, Trainees’ performances after two hours on a scenario were the use of these techniques has not been reported in the pediatric comparable to experienced subjects’ performance on the same population. We report our experience with ME/NBI in scenario. Experts were initially faster and smoother yet saw less pediatric patients. mucosa, but as cases progressed statistically significant differ- Methods: 7 patients underwent upper endoscopy using the ences disappeared. All subjects demonstrated statistically sig- Olympus GIFQ-160Z magnification endoscope and NBI was nificant learning over time. Coaches’ performance was superior utilized in 3 patients. Reasons for use of ME/NBI included to experienced colonoscopists. known Barrett’s esophagus (2) and celiac disease (5). Conclusions: This study showed the overall benefit of pro- Results: Using these techniques endoscopists reported cedural simulator training but failed to find a significant effect improved visualization of Barrett’s esophagus with ability to of coaching in this training paradigm. Future studies should target biopsies to metaplastic areas and improved evaluation of examine transfer of training to actual colonoscopies. villous architecture in vivo. In one patient with dietary and steroid refractory celiac disease who underwent 5 endoscopic 142 evaluations (2 ME, 3 conventional endoscopy) by a single endoscopist, endoscopic to histologic correlation was improved MAGNETIZATION TRANSFER (MT) MRI DETECTS with ME versus conventional endoscopy. On both occasions, INTESTINAL FIBROSIS, NOT INFLAMMATION ME correctly identified both normal villi in the distal duodenum Jeremy Adler1, Scott D. Swanson3, Phyllissa Schmiedlin-Ren2, and abnormal appearing villi in the duodenal bulb (histologic Peter D. Higgins2, Trevor Verrot2, Ellen M. Zimmermann2.

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1Pediatric Gastroenterology, 2Gastroenterology, 3Radiology, including GI. A claim is a compensatory demand by a patient University of Michigan, Ann Arbor. and must be reported by the physician to their insurance company. A claim may be initially closed, or become a lawsuit Background: Crohn’s disease (CD) causes chronic relapsing before it is settled or taken to trial and then closed. intestinal inflammation often leading to fibrosis and intestinal Results: In the 20 yr analysis, 102 physicians were involved in obstruction. There currently are no noninvasive methods of GI claims: 76% were board certified, 74% were US medical identifying fibrosis. We previously demonstrated that MT-MRI school graduates, and 76% were between ages 35–54. 63% of is sensitive to quantitatively detecting intestinal fibrosis in an involved physicians had previous claims experience. The most animal model of CD. We hypothesize that MT-MRI can also frequently identified medical misadventures were (1) errors in differentiate intestinal fibrosis from inflammation. diagnosis, (2) improper performance of procedures, and (3) Methods: Peptidoglycan-polysaccharide (PGPS) was injected having associated issues such as consent/medical records. into the bowel wall of Lewis rats at laparotomy. Control rats Improper performance of a procedure comprised 22% of were injected with human serum albumin (HSA). Additional medical misadventure claims. Colonoscopy was the procedure rats received trinitrobenzenesulfonic acid (TNBS) via enema. most frequently involved. The most commonly reported Control rats received phosphate buffered saline (PBS). Rats claim outcome was settlement (80%). Of 1,202 closed claims were scanned in Varian Inova 2.0 T, 31 cm clear bore system involving patients <18 yrs in 2005, only 7 were within GI. with Acustar S-180 actively shielded gradients. In vivo Conclusions: It is common that physicians involved in claims MR images were obtained at 10 kHz (Msat) and 100 kHz have had previous claims experience. Less than a quarter of the (M0) off-resonance. MT ratio (MTR) of bowel wall was calcu- medical misadventure claims involved the performance of a lated as 100(1 Msat/M0). Rats were killed and intestinal wall procedure. The majority of claims were settled out of court. thickness was measured. Tissue was homogenized, and Western blots were probed with anti-collagen type I antibody. 144 Results: MT-MRI demonstrated significant difference in MTR between PGPS (n = 12) and HSA (n = 5) injected rats (22.5 1.7 ROLE OF DOPPLER ULTRASOUND IN vs. 9.8 1.3; P = 0.0004). No difference was found between INFLAMMATORY BOWEL DISEASE WORKUP 1 1 2 TNBS (n = 3) and PBS (n = 3) rats (23.2 3.0 vs. 19.5 2.1; Veronica B. Busoni , Marina Orsi , Claudia Diaz , Laureana 1 2 1 1 P = 0.598). PGPS rats developed thickened fibrotic intestines. Olleta , Alberto Seehaus , Daniel D’Agostino . Pediatric 2 TNBS developed thickened inflamed, non-fibrotic tissue. MTR Gastroenterology, Radiology, Hospital Italiano Buenos Aires, correlated with tissue thickness (R2 = 0.318) in PGPS and HSA. Buenos Aires, Argentina. MTR did not correlate with tissue thickness in TNBS and PBS (R2 = 0.018). MTR correlated with tissue collagen in PGPS Introduction: Children with inflammatory bowel disease (R2 = 0.639) and TNBS (R2 = 0.401). (IBD) initially have nonspecific symptoms as abdominal pain, Conclusion: MT-MRI is sensitive at detecting tissue fibrosis, diarrhea, loss of appetite or inadequate weight gain. It is and not sensitive at detecting inflammation. This supports our sometimes difficult to establish the need for invasive diagnostic hypothesis that MT-MRI can be used to differentiate intestinal procedures when there are still no bloody stools. fibrosis from inflammation and could be a useful tool for Aim: To determine the diagnostic value of the transabdominal distinguishing fibrotic from inflammatory strictures in CD. ultrasonography (US) of the bowel with Doppler sonography of the superior mesenteric artery (SMA) in the workup of children 143 with possible IBD. Material and Methods: 61 patients were evaluated: 29 patients PEDIATRIC MALPRACTICE DATA IN with Crohn’s disease (CD) (Group I): 20 male, 9 female; age GASTROENTEROLOGY: USE OF THE PIAA 12.5 (r 5–20) and 32 patients with Ulcerative Colitis (UC) CLAIM DATABASE (Group II): 21 male, 11 female; age 14 (r 4–20). The diagnosis 1 2 2 Laurie Conklin , Lori Bartholomew , Catherine Bernstein , of CD and UC was established by clinical features, radiology, 1 1 Maria Oliva-Hemker . Division of Pediatric Gastroenterology endoscopy, and histology. 30 healthy controls (Group III) were and Nutrition, Johns Hopkins School of Medicine, Baltimore, also evaluated: 14 male, 16 female; age 11.5 (r 4.5–18). 2 MD; Physician Insurers Association of America, Rockville, Abdominal B-mode US and color Doppler examination with MD. high frequency transducers (3.5 and 7.5 MHz) was performed with a General Electric 700 (pro Senes) sonographer with a Background: Gastroenterologists may perceive themselves to single operator. SMA flow parameters: resistance index (RI) be at high legal risk due to performance of procedures. There is (n = 0.9 0.1) and peak systolic velocity (PSV) (n = 180–220). little published information about malpractice within pediatric Intestinal wall thickness (n 3 mm). gastroenterology (GI). The Physicians Insurers Association of Results: The intestinal wall thickness was abnormal in 89% America (PIAA), an association of malpractice insurance (26/29) of Crohn’s disease group (mean = 4.4 mm (SD 1.61) and companies, maintains a database of claims submitted by its in 50% of Ulcerative Colitis group (mean = 3.4 mm (SD 1.34), 40 members. The goal of this study was to evaluate GI claim showing a statistically significant difference with healthy con- data among cases involving children. trols group (mean=1.63, SD 0.33) (P < 0.0001). The detection Methods: Closed claims involving patients <18 years of age of increased wall thickness in US was 100% specific for both submitted to the PIAA database from 1/1/85 to 12/31/05 were CD and UC, but sensitivity was 89% for CD and 50% for UC. analyzed. A secondary analysis from 2005 only examined No statistically significant difference was seen in RI or PSV claims in patients <18 yrs within multiple subspecialties, between three groups.

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Conclusion: The intestinal wall thickness was the best 1Pediatrics, Walter Reed Army Medical Center, Washington, diagnostic marker in Doppler US evaluation during the initial DC; 2Medicine, Mucosal Biology Research Center, Baltimore, stage of IBD, when the clinical symptoms are subtle and non MD; 3Pediatrics, USUHS, Bethesda, MD; 4BHNRC, USDA, specific, before undertaking diagnostic invasive procedures as Beltsville, MD. endoscopic interventions. Background: A common feature of nematode infection is a Th2 dependent decrease in tissue resistance and transcellular ORAL ABSTRACT PRESENTATIONS glucose transport. The main epithelial transporters for glucose BASIC BIOLOGY OF THE INTESTINE AND LIVER uptake are SGLT-1 and GLUT2. Th2 cytokines stimulate FRIDAY, OCTOBER 26, 2007 arginase-1 (arg-1) activity in AAMF. 2:00 PM – 4:00 PM Aim: To determine the role of AAMF to nematode induced changes in epithelial function. 145 Methods: Mice were studied 9 days after N. brasiliensis (Nb) infection. Groups of mice received 0.2% of BEC, an arg-1 ROLES OF NETRIN BIOSYNTHESIS BY ENTERIC inhibitor, in drinking water or vehicle. Muscle-free jejuni were NEURONS IN THE GUIDANCE OF VAGAL SENSORY placed in Ussing chambers to determine responses to glucose or AXONS TO THE FETAL GUT in microsnapwells to determine transepithelial resistance 1 1 2 Elyanne Ratcliffe , Monique Anderson , Alcmene Chalazonitis , (TER). Expression (fold change) of cytokines and AAMF 2 1 2 Michael Gershon . Pediatrics, Pathology and Cell Biology, markers were measured by real-time PCR. Columbia University, New York, NY. Results: Nb infection upregulated Th2 cytokines (IL-13, 4.0 1.5) and AAMF markers (CD206, 3.2 0.5; arg-1, 8.5 3.1). Vagal sensory axons navigate to specific sites in the bowel during This was associated with decreased mucosal resistance and fetal life. Netrins, in the mucosa and outer gut mesenchyme act on glucose transport. Infection did not alter the expression of the their receptor, deleted in colorectal cancer (DCC), to attract SGLT1, but reduced GLUT2 to 10% of that in control mice. BEC neural crest-derived (CD) cells and vagal sensory axons. To did not alter the ability of Nb to upregulate IL-13 (4.4 0.2) or study the relationship between the establishment of the vagal AAMF (CD206, 2.6 0.9; arg-1, 6.3 3.7) and did not prevent sensory innervation to that of the enteric nervous system, Nb-induced decrease in resistance. In contrast, BEC attenuated the pattern of vagal sensory innervation was compared in the Nb-induced decrease in glucose transport, associated with an ganglionated and aganglionic bowel. DiI was applied bilaterally improvement in GLUT2 expression to 40% of control levels. / to nodose ganglia of Ret mice, which lack ganglia in the Conclusions: Inhibition of arg-1 in AAMF does not interfere subdiaphragmatic bowel, and their wild-type littermates. with the development of the Th2 response or AAMF. Arg-1 Descending vagal sensory axons stopped when they reached activity does not mediate Nb-induced changes in barrier func- / the aganglionic region of the Ret gut. Netrin-immunoreactiv- tion, but plays a key role in the reduction of glucose absorption. ity was evident in the mucosa, outer gut mesenchyme, and This data supports a novel interaction between AAMF and neurons of wild-type mice, but was deficient in the aganglionic nutrient absorption in epithelial cells. bowel. CD and non-crest-derived (nCD) cells were isolated from E15 rat gut by positive and negative immunoselection with antibodies to p75NTR. Only nCD cells were found by RT-PCR Control BEC Nb Nb+BEC to express transcripts encoding netrins-1 and -3. In contrast, mRNA encoding netrins-1 and -3 were detected in cultures of TER 32.4 3.3 45 6.7 3.8 1.0 9.7 2.2 w neurons (from CD cells). To determine whether enteric neurons Glucose 175 38 236 38 21 10 137 40 uptake as well as synthesize netrins, CD cells were allowed to Values= Mean SE; TER = V cm2; changes in Isc = mA/cm2; give rise to neurons alone or in co-culture with stably transfected P < 0.05; FP.05 vs Nb. 293-EBNA cells that secrete netrin-1 with a cMyc tag. Enteric neurons were netrin-immunoreactive no matter whether they developed in the presence or absence of an exogenous source 147 of netrin-1; in the co-cultures, the 293-EBNA cells but not the THE ROLE OF SMAD-DEPENDENT TGF-BETA neurons were cMyc-immunoreactive. Enteric neurons, but not SIGNALING IN DENDRITIC CELL-MEDIATED their CD precursors, therefore, synthesize netrins. These obser- MUCOSAL HOMEOSTASIS vations are consistent with the idea that vagal sensory nerves are Jonathan M. Gisser, Alex Y. Huang, John J. Letterio. Pediatrics, attracted to enteric ganglia by intrinsic neuron-derived netrins. Rainbow Babies and Children’s Hospital, Cleveland, OH. Failure of vagal axons to find their correct destinations in aganglionic bowel may thus reflect the absence of a neuronal source of netrin. FDHN, CDHNF, NS12969 and NS15547. Dendritic cells (DCs) are professional antigen presenting cells that are found in peripheral tissues including the gut, and play a 146 role in the pathogenesis of Inflammatory Bowel Disease (IBD). As early responders to foreign antigens, DCs are able to polarize ALTERNATIVELY ACTIVATED MACROPHAGES the adaptive immune system toward an anti- or pro-inflammatory (AAMF) PLAY A CRITICAL ROLE IN EPITHELIAL response, depending on the stimulus. However, the mechanism RESPONSES TO ENTERIC INFECTION responsible for this polarization is poorly understood. Recently, Diana Riera1, Rex Sun2, Aiping Zhao2, Jennifer Stiltz2, Transforming Growth Factor b (TGFb) has been identified as a Kathleen Madden3, Joseph Urban4, Terez Shea-Donohue2. key player in this process. TGFb exerts part of its effects via the

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Smad-dependent signaling cascade. Both TGFb and Smad3 null cells in intestinal tissue. Immunofluorescence revealed the mice develop gut inflammation, suggesting a role for Smad3- presence of GFP positive cells in all layers of the gut wall. mediated TGFb signaling in gut homeostasis. However, recent Conclusions: AFS cells have the potential to integrate in the studies in an adoptive transfer model of IBD have shown that developing embryonic chicken guts. Current studies are directed functional Smad3 is not needed in either effector or regulatory at evaluating the differentiation and thus functional potential of T cells to prevent inflammation. Given DC’s role in directing the these cells using a panel of cell specific and functional markers. immune response, we have therefore explored the possibility that This preliminary study is, in our opinion, an important step Smad3-dependent TGFb signaling cascade may play a towards stem cell therapy for intestinal regeneration. central role in the DC’s capacity to maintain oral tolerance. We hypothesize that in the mucosal milieu, TGFb acts through 149 DC Smad signaling to temper the downstream effects of Toll-like receptor binding and polarize the DC to a more tolerogenic TSC2 ACTS ON TARGET OF RAPAMYCIN (TOR) AND phenotype. Our preliminary results indicate that Smad3-deficient P53 TO MODULATE INTESTINAL GROWTH IN THE bone marrow is almost twice as cellular as wild-type (7.3 107 ZEBRAFISH vs. 4 107 cells/mouse) and yields 1.5 times as many DCs in Khadijah Makky, Alan N. Mayer. Pediatrics, Medical College standard culture techniques. Furthermore, the proportion of of Wisconsin, Milwaukee. CD11c+ cells (75%) is increased over wild type (49%). Most strikingly, expression of the CD86 co-stimulatory molecule in The regulation of intestinal growth during development is still these cells in response to lipopolysaccharide challenge is also poorly understood. Recently we implicated the target of increased versus control. This may be a reflection of a larger DC rapamycin (TOR) signaling pathway as a key regulator of population or an intrinsic capacity to up-regulate expression of epithelial growth and morphogenesis in zebrafish intestine CD86 in Smad3-deficient mice. These early results suggest that (Makky et al, Dev Biol 2007;303:501–13). The tuberous sclerosis DCs may be a key effector of Smad3-mediated TGFb signaling complex gene product TSC2 negatively modulates TOR activity, and that functional Smad3-dependent pathway in DC is necessary receiving input from several upstream signaling pathways. This for maintaining gut homeostasis. suggested the hypothesis that TSC2 might regulate intestinal growth via TOR signaling. Specifically, the hypothesis predicts 148 that downregulating TSC2 will lead to an abnormally large intestine. In contradiction to the hypothesis, morpholino- AMNIOTIC FLUID STEM CELLS PARTICIPATE mediated knock down of TSC2 resulted in a smaller gut. IN INTESTINAL ORGANOGENESIS IN A MODEL Morphometric analysis of intestinal cross sections from TSC2 OF GUT DEVELOPMENT ON CHICK knockdown showed a significant reduction in cell number per CHORIOALLANTOIC MEMBRANE section, but the cells were more columnar. We found that TSC2 1,4 2 1 2 Mara Cananzi , M. Metzger , A. Malerba , A. J. Burns , knockdown resulted in both the activation of TOR and the 1 2,3 1 1 A. Pierro , N. Thapar , P. De Coppi . Surgery Unit, UCL induction of p53 and its downstream target p21. Knockdown Institute of Child Health and Great Ormond Street Hospital, of p53 rescued the TSC2 morphant cell number phenotype, 2 London, UK; Neural Development Unit, UCL Institute of Child demonstrating that activation of p53 signaling accounts for the 3 Health, London; Department of Gastroenterology, Great reduction in cell number seen in the TSC2 knockdown. Rapa- 4 Ormond Street Hospital; Department of Pediatrics, University mycin treatment independently modulated intestinal epithelial of Padua, Padua, Italy. cell size and number, suggesting that the TSC2-mediated effect on p53 is separate from its effect on rapamycin-sensitive TOR Background: Gut development represents a challenging field of signaling. Furthermore, rapamycin treatment had no effect on the study, mainly due to the difficulty in establishing in vitro models expression of p53 and p21. Taken together, the data support a of intestinal regeneration. In ovo organ culture of embryonic guts mechanism wherein the down-regulation of TSC2 produces a on chick chorioallantoic membrane (CAM) is an established paradoxical effect: activating TOR to promote growth but also model for studying intestinal development. We have recently activating p53 to inhibit proliferation. Thus p53 may serve in a described amnioticfluidstem (AFS) cells capable of giving rise to developmental capacity downstream of TSC2 to prevent organ multiple cell lineages both in vitro and in vivo. Our aim is to overgrowth in the setting of activated TOR signaling. investigate the potential of AFS cells injected into a model of developing gut maintained on the chick CAM. 150 Materials and Methods: Hindguts dissected from E7-9 chicken (G. gallus) embryos were transplanted on the exposed ROLE OF THE INNATE IMMUNE SYSTEM IN THE CAMs of E7-8 fertilised chicken eggs. After gut placement on PATHOGENESIS OF GLUTEN SENSITIVITY: the CAM expanded AFS cells, obtained from transgenic rats PRELIMINARY RESULTS 1,2 1 1 1 expressing green fluorescent protein (GFP), were injected into Anna Sapone , L. Imbrici , M. Cammarota , M. Guiliano ,M. 1 1 1 1 1 the intestinal lumen (1.5 105 cells/gut). Eggs were then incu- DeRosa , M. Carteni , C. Tolone , A. Papparella , G. Paolisso , 1 1 2 1 bated at 378C for 7 days and finally sacrificed. The presence of V. Familiari , L. DeMagistris , A. Fasano . Second University 2 AFS cells in the guts was evaluated through amplification of the of Naples, Napoli, Italy; University of Maryland, Baltimore. enhanced green fluorescent protein (EGFP) gene and immunofluorescence for GFP. Background: Reaction to gluten can involve allergic (wheat Results: EGFP gene amplification on genomic DNA extracted allergy), non-allergic [gluten sensitivity (GS)], or autoimmune from the transplanted guts demonstrated the presence of AFS [celiac disease (CD)] mechanism. Recent evidences suggest

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E58 that early changes in intestinal permeability (IP) may play a spectrometry. Stringent criteria established 4 proteins that pivotal role in the pathogenesis of CD also through a Toll-Like were overabundant in all PN samples compared to BA: Receptor signaling pathway (TLRs) involvement. Conversely, peroxiredoxin-4, serotransferrin, glutathione S-transferase P, no data are currently available on the role of intestinal barrier and Mn-superoxide dismutase (mitochondrial SOD), each dysfunction in the pathogenesis of GS. involved in redox regulation and cellular protection against Aims: To investigate the changes in IP, TJ protein genes oxidative stress, a proposed mechanism involved in PNALD expression and TLRs in GS. (Am J Physiol 1996;270:G691). Two overabundant proteins in Methods: Biopsy were obtained from 12 GS patients, 24 patients BA were peroxiredoxin-2 and protein S100-A8. These findings with active CD, 3 patients with CD in remission, and 14 healthy were validated with immunoblotting. controls. TJ gene expression of Claudin (CL) 1, CL2, CL3, CL4, Conclusions: Through comparative proteomics, a network of ZO-1 and of TLR1, TLR2 and TLR4 were investigated by proteins involved in redox regulation was shown to be over Real-time PCR. IP was evaluated by means of the lactulose/ abundant in PNALD, suggesting that oxidative stress is a key mannitol test (LA/MA). pathway of tissue injury and could be a target for novel Results: CL4 expression was increased threefold in GS subjects therapeutic approaches in this disease. compared to both CD patients and healthy controls, while no changes in CL1, CL2, CL3, and ZO-1 expression were detected. IP in GS patients (0.014 0.015) was similar to that detected in 152 healthy controls (0.019 0.018). Conversely, in CD patients an ANTIGEN-IGE COMPLEXES INDUCE CD23- overexpression of both CL1 and CL2 was observed and was DEPENDENT UPREGULATION OF CCL20 IN associated to an increase in IP (0.052 0.048). TLRs expression HUMAN INTESTINAL EPITHELIAL CELLS IN was measured in a random subgroup of CD (N = 10), GS (N = 4) FOOD ALLERGIC DISEASE patients and normal subjects (N = 4). TLR1 resulted significantly Mirna Chehade1, Hongxing Li2, Huabao Xiong2, Lloyd Mayer2, increased in CD in respect to the GS and normal controls M. Cecilia Berin1,2. 1Pediatrics, 2Immunology Institute, (P < 0.05), while an overexpression of TLR2 and TLR4 was Mount Sinai School of Medicine, New York. detected in both CD and GS groups compared to normal controls. Conclusions: These results show that the pathogenesis of GS is Introduction: In food allergic individuals, exposure to food different from that of CD and does not involve the loss of allergens can trigger immediate local intestinal hypersensitivity intestinal barrier function. The over expression of TLRs in CD reactions followed by late-phase inflammatory response. We and GS could suggest an important role of innate immune have shown that the low affinity IgE receptor CD23 is constitu- system in both conditions. tively expressed by intestinal epithelial cells and participates in allergic reactions by mediating the uptake of antigen-IgE 151 complexes. The role of CD23 in the initiation of intestinal UPREGULATION OF REDOX PATHWAY PROTEINS inflammation has not been examined. We hypothesized that IN LIVERS FROM INFANTS WITH PARENTERAL antigen-IgE complexes could trigger via CD23 an epithelial NUTRITION-ASSOCIATED LIVER DISEASE (PNALD) cell-generated inflammatory cascade, by upregulating pro- Ronald J. Sokol1, Keri Murray1, Jenna Boyd1, Heather inflammatory chemokines such as CCL20. Thompson1, Ross Shepherd2, Cara L. Mack1, Frederick M. Methods: Human Caco-2 cells were grown on transwells and Karrer1, Mark Duncan1. 1Pediatrics, University of Colorado stimulated with human IgE-antigen complexes. CCL20 mRNA School of Medicine and The Children’s Hospital, Denver; was measured by real-time PCR, and secreted CCL20 by 2Pediatrics, Washington University School of Medicine, St. Louis, ELISA. Endogenous CD23 expression was knocked down MO. by siRNA. Formalin-fixed, paraffin-embedded duodenal biopsy sections of patients with IgE-sensitization to foods, Background: An important complication of prolonged treat- with or without allergic eosinophilic gastroenteritis (AEG), ment with parenteral nutrition (PN) in infants with intestinal were used. Non-allergic patients with gastrointestinal symp- failure is the development of PNALD. Because the pathogenesis toms and normal duodenal biopsies were used as controls. of PNALD is poorly understood, new strategies are needed to Immunohistochemical staining for CCL20 was performed discover pathogenic mechanisms involved in this condition. using a mouse monoclonal antibody and corresponding isotype The aim of this study was to examine protein networks involved control. in PNALD by the application of comparative proteomics. Results: Stimulation of Caco-2 cells with antigen-IgE com- Methods: A portion of surgical liver biopsies, obtained clinically plexes induced significant upregulation of CCL20 mRNA before 5 months of age, was flash-frozen immediately in liquid expression and CCL20 release on the basolateral side of the nitrogen from 7 infants with PNALD and from 7 with biliary monolayer. Antigen or IgE alone had no effect. CCL20 release atresia (BA control group) undergoing portoenterostomy. Liver in response to antigen-IgE complexes was inhibited by knock- was homogenized, proteins precipitated by methanol/chloro- down of CD23 expression. CCL20 expression in duodenal form, and difference gel electrophoresis (DIGE) was used to biopsies was patchy, and was restricted to epithelial cells in compare protein levels in PNALD and BA samples (n = 7 separate the villi and the base of the crypts. CCL20 staining was found in gels). Differentially abundant spots were excised, digested with 4/6 patients with IgE sensitization + AEG, 2/6 patients with IgE trypsin, analyzed by MALDI-TOF MS and identified based on sensitization, and 10/13 non-allergic controls. their peptide mass fingerprints. Conclusion: Antigen-IgE complexes are capable of initiating a Results: Over 2000 protein spots were detected on each gel and CD23-dependent release of the chemokine CCL20 in the 96 of the differentially abundant spots were identified by mass intestinal epithelium.

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POSTER SESSION III 154 SATURDAY, OCTOBER 27, 2007 GASTROESOPHAGEAL ACID EXPOSURE IN INFANTS 8:00 AM – 10:00 AM IS LARGELY DUE TO TWO SPECIFIC TYPES OF ACID REFLUX EVENTS THAT ARE DISTINGUISHABLE ON Esophagus/Stomach THE BASIS OF UNIQUE PATTERNS OF BOLUS CONTACT TIME AND CHEMICAL CLEARANCE 153 Frederick W. Woodley1,3, John Hayes2, Hayat Mousa1. 1Gastroenterology, Hepatology and Nutrition, 2Columbus EFFECT OF PROPOFOL ON ACID Children’s Research Institute, 3Center for Healthy Weight and REFLUX MEASURED WITH THE BRAVO Nutrition, Columbus Children’s Hospital, Columbus, OH. pH MONITORING SYSTEM Anupama Chawla, Frances G. Turcotte, Grace Walker, Jeffrey Background: Combined esophageal pH monitoring (EPM) and A. Morganstern. Pediatrics, Stony Brook University Hospital, multichannel intraluminal impedance (MII) reveals 4 unique Stony Brook, NY. types of acid gastroesophageal reflux (AGER) episodes in infants. Each type can be distinguished based on the presence Background: Wireless and some wired pH probes are placed or absence of detectable intraluminal flow (volume clearance; under sedation usually with propofol. It is unclear whether VC) and characteristic temporal relationships between VC and sedation or the required pre-sedation fasting influences the chemical clearance. EPM/MII was used in this study to assess frequency or magnitude of reflux during the study. Our results AGER in infants on the basis of event types I through IV. may help identify a post-anesthesia period during which pH Methods: EPM/MII tracings from 12 symptomatic infants studies may not be reliable. (<12 mo) were examined. Mean frequencies, mean durations Methods: The pH tracings of 10 children evaluated for GER with and percentages of the total gastroesophageal acid exposure placement of the Bravo capsule under propofol were analyzed (GAE) due to each AGER event type were calculated. over a 48 hr period. The first 24 hr pH tracing was compared to the Results: Of 926 total AGER episodes, 23.1% were type I, 6.3% second 24 hr period. Each 24 hr period was subgrouped into 6 hr were type II, 69.1% were type III, and 1.5% were type IV. In segments for comparison. Six hr segments from day 1 were 20.2 hours of combined GAE, 52.3% occurred during type I, compared to corresponding 6 hr segments on day 2. 2.3% occurred during type II, 42.4% occurred during type III, and Results: The fraction of time the pH was <4 was significantly 3.0% occurred during type IV. Types I and III were both more less on day 1 compared to day 2. The 1st 6 hr segment on day 1 frequent than types II (P =.002and<.0001) and IV (P = .002 and (following propofol induced anesthesia) had significantly less <.0001), respectively. Type I and type III frequencies were not acid reflux compared to its corresponding segment on day 2. different (P = .369). Whereas increasing AGER indices were not Discussion: Duration of acid reflux in the segment immediately correlated with specific patterns/ratios of AGER type (either following propofol induced anesthesia was suppressed and this frequency or duration) (P >.05), increasing numbers of AGER was also reflected in the total duration of acid reflux over the 24- episodes were strongly correlated with increasing numbers of hour period. Our data suggest that the monitoring of pH within type III events (R2 = .9426). 6 hours post-anesthesia may not be reliable. This period may Conclusion: In infants: 1) total GAE is largely due to event types need to be disregarded when analyzing the pH recording in I and III, 2) types I and III comprise the majority of total AGER these patients. NPO status, effects of propofol on GI physiology, events, 3) increasing frequency of total AGER is strongly corre- decreased oral intake and lack of activity after anesthesia are all lated with type III events, and 4) increasing AGER indices are not potential contributing factors. This study is limited by its correlated with predictable patterns/ratios of AGER event types. inability to control for quality and quantity of food intake and patients’ activity level. We plan to conduct a larger pro- 155 spective study controlling for these factors. ‘‘pH ONLY’’ ACID REFLUX EVENTS THAT OCCUR Abstract 153 Table A. Reflux Monitoring on Day 1 and Day 2 DURING LATER PHASES OF THE FEEDING CYCLE Using Bravo IN INFANTS ARE LESS ACIDIC AND CLEARED MORE EFFICIENTLY THAN CLASSIC TWO-PHASE ACID Day 1 Day 2 P value REFLUX EVENTS Frederick W. Woodley1,2, Hayat Mousa1. 1Gastroenterology, No. of reﬂux episodes (mean SD) 48.2 31.6 57.6 36.4 0.157 Hepatology and Nutrition, 2Center for Healthy Weight and Fraction of time pH <4 (mean SD) 2.4 2.5 4.2 3.5 0.048 Nutrition, Columbus Children’s Hospital, Columbus, OH.

Abstract 153 Table B. Reflux Monitoring of 6-Hour Segments on Day 1 and Day 2 1st 6 hrs 1st 6 hrs 2nd6hrs 2nd 6 hrs 3rd 6 hrs 3rd6hrs 4th 6 hrs 4th 6 hrs Day 1 Day 2 Day 1 Day 2 Day 1 Day 2 Day 1 Day 2

No. of reﬂux episodes (mean W SD) 24 W 14.1 26.9 W 22.2 13.9 W 16.8 14.8 W 16.7 1.1 W 1.7 2.6 W 3.7 9.2 W 5.1 13.4 W 11.3 Fraction of time pH<4 (mean W SD) 3.63 W 2.65 6.54 W 6.15 3.97 W 6.00 5.51 W 9.65 0.32 W 0.94 1.60 W 4.40 1.71 W 1.79 3.21 W 3.42

P < 0.05.

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Background: We previously reported that gastroesophageal 42, range 1–119/pt) were recorded. Of the total POEs, 71 (9.5%) acid exposure (GAE) in infants is a function of four types of acid were temporally correlated with an RSE (40 Cs [56.3%], 7 Chs gastroesophageal reflux (AGER): I) events that are cleared by [9.9%], 14 Ws [19.7%], and 10 As [14.1%]). Of the total RSEs, overlapping volume clearance (VC) and chemical clearance 110 (15.3%) (71 Cs [64.6 %], 7 Chs [6.4 %], 16 Ws [14.5%], and (CC) components, II) events that are cleared by concurrent VC 16 As [14.5%]) were temporally correlated with a POE. Across and CC, III) events that are cleared by CC only, and IV) AGER all RSEs, 1 patient had a positive SI and a positive SSI, and events that are superimposed. Types I and III comprise the 3 others had only a positive SSI. Only 1 patient (5.3%) (1 of the majority of total events and are responsible for the majority of 3 with a positive SSI), however, also had a significant SAP; this GAE in infants. Pathogenicity of AGER involves variables that patient also had significant chi square and z scores. include the frequency, duration and pH of AGER events. The Conclusions: POEs are not strongly associated with RSEs that purpose of this investigation was to compare AGER event types have been linked previously with GER. This result should be I and III, on the basis of these variables, during discrete periods interpreted carefully and in full consideration of the patient related to feeding. population and the frequency of their respective RSEs. Methods: Impedance/pH tracings from 12 symptomatic infants (median 20 wks) were examined. Mean frequencies, durations, 157 and nadir pH values were calculated during feeding, 1st hour post-prandial [1stPP], 2ndPP, and fasting. FACTORS PREDICTING OUTCOME IN 760 Results: Compared to type I events, type III events were: 1) PEDIATRIC PATIENTS UNDERGOING remarkably more frequent during 2ndPP (5-fold) and fasting PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (3-fold), 2) cleared significantly more efficiently during 1stPP (PEG) 1 2 2 2 (3-fold, P = .02), 2ndPP (3-fold, P = .0001), and fasting (4.5-fold, John E. Fortunato , Carmen Cuffari , April Troy , Erin Davis , 1 2 2 P <.0001), and 3) less acidic during 2ndPP (1.9 0.15 vs Matthew Loza , Maria Oliva-Hempker , Kathleen Schwarz . 1 2.6 0.07, P = .0005) and fasting (1.5 0.12 vs 2.9 0.07, Peds GI, Wake Forest University, Winston-Salem, NC; 2 P <.0001). Whereas clearance of type I events became increas- Peds GI, Johns Hopkins University, Baltimore, MD. ingly less efficient, clearance efficiency of type III events did not fluctuate significantly over the course of the feeding cycle. Background: PEG is an accepted approach for gastrostomy Conclusions: Lower acidity and greater clearance efficiency of tube placement in children; however, the need for preoperative type III events suggest that they may be less pathogenic than screening measures is not well defined. type I events during later phases the feeding cycle. Aim: Identify factors associated with poor PEG outcome. Methods: A retrospective review was performed of 760 156 (407M;353F) PEG patients at The Johns Hopkins Children’s Center from 1994–2005. Follow-up for 1 year was available in ARE ‘‘pH ONLY’’ ACID GASTROESOPHAGEAL 684 patients. Logistic regression or multiple linear regression REFLUX EPISODES IN INFANTS TEMPORALLY was used to analyze: indication, diagnosis, age, prematurity, CORRELATED WITH RESPIRATORY SYMPTOMS? neurological impairment (NI), weight-for-age z-scores, modi- 1,3 2 1 Frederick W. Woodley , John Hayes , Hayat Mousa . fied barium swallow (MBS), postoperative complications, need 1 2 Gastroenterology, Hepatology and Nutrition, Columbus for fundoplication (FP), gastrojejunal tube (GJ), or jejunostomy, 3 Children’s Research Institute, Center for Healthy Weight and and length of hospital stay (LOS). Nutrition, Columbus Children’s Hospital, Columbus, OH. Results: The median (range) age was 1 year (0–26 years). The most common indications for PEG were failure to thrive (FTT) Background: ‘‘pH only events’’ (POEs) are acid gastroeso- (n = 371) and dysphagia (n = 274). NI was diagnosed in phageal reflux events that are detectable by pH but not by 322 patients and prematurity in 206. Postoperative FP, GJ or impedance. POEs contribute significantly to total acid GER in jejunostomy were required in 66, 24, and 9 patients, respect- infants. The clinical significance of POEs in infants has not ively. Preoperative dysphagia (vs. FTT), preoperative direct been tested. aspiration on MBS, and younger age strongly associated with Aim: To test the clinical importance of POEs by attempting to need for FP after PEG (P = 0.008, OR 2.4; P = 0.013, OR 5.2, temporally correlate POEs with respiratory symptom events and P = 0.001, OR 0.83, respectively). Prematurity and NI also (RSEs) suggestive of GER as an etiology. associated with need for FP (P = 0.06, OR 1.3) and (P = 0.08, Methods: Combined EPM/MII tracings from 15 symptomatic OR 1.2), respectively. Subjects with preoperative dysphagia had infants (< 12 mo, median 3.5 mos) were examined for POEs a longer median LOS of 8 days (P < 0.00001). NI patients had and RSEs (coughs [Cs], gagging [Gs], choking [Chs], wheezing greater weight gain than neurologically normal after PEG [Ws], and apnea [As]). RSEs that occurred either during or (P = 0.04). Postoperative complications were observed in 28 5 min after a POE were tagged as being temporally correlated of 747 children, most commonly, wound infection (n = 19) and with a POE. Symptom indices (SI), symptom sensitivity indices pneumonoperitoneum (n = 4). Preoperative diagnosis, indica- (SSI), symptom association probabilities (SAP), chi square tion, prematurity, and NI did not influence postoperative values, and z scores were calculated across all RSEs for each complications. subject. SI, SSI, and SAP were considered positive when 50%, Conclusions: PEG is a safe and effective method for enteral 10%, and 95%, respectively. Chi square and z scores were access in children. Future prospective studies are needed to considered significant when associated p values were < .05. determine if dysphagia and prematurity are associated with Results: 751 total POEs (median 33, range 4–207/pt) and 721 esophageal motility disorders predisposing patients to GERD total RSEs (479 Cs, 7 Gs, 21 Chs, 32 Ws, and 182 As; median after PEG and need for FP.

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158 Background: Late complications of esophageal atresia (EA) are increasingly recognized. Endoscopy as needed can detect INCREASED INTRAGASTRIC pH WITH PROTON esophagitis and Barrett’s esophagus. It is not clear whether PUMP INHIBITOR (PPI) RESULTS IN EROSIVE systematic endoscopic surveillance in these patients is ESOPHAGITIS (EE) HEALING IN PEDIATRIC beneficial, irrespective of the presence or absence of symptoms. GASTROESOPHAGEAL REFLUX DISEASE (GERD) The aim of our study was to describe the macroscopic and Benjamin D. Gold1, Eric Lloyd2, Stuart Atkinson2. 1Pediatrics, 2 microscopic endoscopic findings in relation to patients’ Emory University School of Medicine, Atlanta, GA; R&D, TAP symptoms. Pharmaceutical Products Inc., Lake Forest, IL. Methods: All patients referred to our EA multidisciplinary Background: Studies suggest that control of intragastric pH is clinic from October 2005 until May 2007 were routinely essential to reduce esophageal acidification, with its risk for proposed to undergo an endoscopic evaluation. Data regarding GERD and associated complications. Recent data from adult their digestive symptoms were prospectively collected. Macro- studies with a proton pump inhibitor (PPI) demonstrate a scopic appearance and histologic findings were analyzed. The relationship between intragastric pH elevation and esophageal endoscopy was considered normal if no esophagitis, Barrett’s healing as well as symptom resolution. (Katz, DDW, 2006) esophagus (intestinal metaplasia) or gastric metaplasia was Objectives: The aim of this retrospective analysis was to assess found. Patients with a gastric tube, dilated stricture or recurrent the relationship between intragastric pH and EE resolution and tracheo-esophageal fistula at the time of endoscopy were symptom reduction when a PPI was administered to pediatric excluded. subjects. Results: 24 patients (12 girls) with a median age of 7.3 years Methods: An open-label multicenter (11 sites) study included (5 m to 17.5y) at the time of endoscopy were evaluated. The 66 children aged 1–11 years (mean 7.0 years) with symptomatic most common type of EA was type C (n = 19; 79%). 33% had GERD (Tolia, JPGN, 2002). Subjects were administered lan- had a long gap atresia (n = 8). 54% (n = 13) had a normal soprazole 15 mg (30 kg, n = 32) or 30 mg (>30 kg, n = 34) endoscopy, 33% (n = 8) had esophagitis and 33% (n = 8) had once daily for 8–12 wks; 24 subjects required dosage increases gastric metaplasia. No intestinal metaplasia or adenocarcinoma up to 60 mg daily at investigator discretion. Assessments were found. No digestive symptoms were predictive of an included: 12 and 24-hr intragastric and intraesophageal pH abnormal endoscopy except dysphagia. on day 5, EE healing (n = 27) at wk 8, and GERD symptom Conclusion: This study shows that dysphagia can be pre- response. dictive of an abnormal endoscopy in patients with EA. Results: Overall, EE resolved in 100% of the 27 subjects by wk Further endoscopic follow-up is still needed to evaluate 12. Over 80% of subjects had resolution (significant to complete) the outcome of the frequent gastric metaplasia in patients of GERD-related symptoms and overall improvement in with EA. physician global assessment. There was a significant association between intragastric pH control at day 5 (% of time pH >4.5) and EE healing by wk 8 (P < 0.008). Of the 20 GERD-related 160 symptoms assessed, 7 symptoms had a significant decrease that NON-ACID GASTROESOPHAGEAL REFLUX IN correlated with intragastric pH elevation, namely belching, CHILDREN WITH RESPIRATORY SYMPTOMS cough, irritability with meals, wheezing, anorexia, nausea, and EVALUATED WITH THE 24 HOUR MULTICHANNEL abdominal pain. Intraesophageal pH did not correlate with INTRALUMINAL IMPEDANCE-pH PROBE symptom resolution and/or EE healing. Judith Cohen, Marina Orsi, Gabriela Donato, Laureana Olleta, Conclusions: In this trial, day 5 intragastric pH demonstrated a Daniel D’Agostino. Pediatric Gastroenterology, Hospital significant association between both esophageal healing and Italiano, Buenos Aires, Argentina. GERD symptom resolution. Additional prospective studies are needed to further explore the correlation between symptoms and Background: The ability of the 24 hr Multichannel Intralum- day 5 pH. inal Impedance-pH to study the number and duration of non acid/acid episodes may help us understand if the variety of 159 clinical presentations are because there is a different behaviour ENDOSCOPIC FINDINGS IN CHILDREN WITH in children with silent gastroesophageal reflux. ESOPHAGEAL ATRESIA DURING SYSTEMATIC Aim: To evaluate with the 24 hour Multichannel Intraluminal FOLLOW-UP: RELATIONSHIP TO Impedance-ph probe(MII-pH) the presence of acid or non acid SYMPTOMATOLOGY episodes in children with respiratory symptoms and with the Julie Castilloux1, Dorothe´e Dal Soglio2, Christophe Faure1. classic digestive presentation at different age. 1Pediatric Gastroenterology, 2Pathology, Ste-Justine Hospital, Methods: Since January 2005 to December 2006, a prospective Montreal, QC, Canada. study was conducted in 198 children. Patients were divided Abstract 159 Table Regurgitation Pyrosis Dysphagia Odynophagia Food impaction Coughing at meals

Abnormal endoscopy 2/11 3/11 7/11 0/11 4/11 2/11 Normal endoscopy 3/13 1/13 3/13 1/13 4/13 3/13

P < 0.05 vs normal endoscopy OR 5.83 [95%CI: 1.04–32.6] (Chi-square test).

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E62 according age in GI <2 yr; GII >2 yr and due to symptoms in Aim: To study with the MII-pH the presence of acid (A)/non Respiratory (R) or Digestive (D). The evaluation was performed acid (NA) GER in group of severe asmathic children and during one day with a Sleuth Monitoring Recorder using monitor response to proton pump inhibitors (PPI). catheter with 7 impedance sensors and one pH probe at the Material and Methods: Since May 2005 to April 2007, distal end. 44 children (6–14 yr) with persistent asthma (inadequate Results: 198 children were evaluated (male 103, female 95); symptom response to at least 4 months treatment with flu- mean age 2.9 years SD 3.5, range 0.06–17, median 1.91. The ticasone) were evaluated. The MII-pH was performed one number of NA GER by impedance was significantly increased day. If the study was abnormal children were given PPI at in GI to GII (P < 0.001). No difference was found in the number dose 1,2 mg/kg/d b.i.d. maximum dose of 40 mg/d. After 2 of acid events with age and clinic presentation. There is months on PPI treatment, a second MII-pH was done and if statistical difference in Non acid reflux between younger with this one was still pathologic the medication was increased elder children and in the total number of episodes with MII in to double dose with a maximun of 60 mg/day and after the D to R group. Instead there is no statistical difference in the other 8 weeks the third monitoring was repeated. Functional acid behavior between both groups. tests were performed at diagnosis and after GER was con- Conclusions: A more non-acid pattern of gastroesophageal trolled. reflux was seen with the MII-pH in respiratory patients particu- Results: 18/44 (40%) GER in asmathic children.On PPI the pH larly in the smaller ones with no difference in the number of acid score improved, the number of A episodes decreased but NA events in either group. events increased. Although no change was seen in pulmonary function, score according to number of days without asthma, nocturnal symptoms and the need of beta2 or steroids showed Acid/Non-acid Episodes by MII in Digestive and Respiratory definite improvement. Patients at Different Ages Conclusions: GER was observed in 40% children with severe asthma. Most patients presented clinical improvement on conventional or double dose of PPI treatment. They reduced the Digestive Respiratory number of days without symptoms and the requirements of Acid, Med Non- Med Acid, Med Non- Med asthma medication although no difference in FEV function was Age N Acid, N N Acid, N seen. Those with persistent or increased NA reflux with no response after increasing PPI need another therapeutic < 1.91 years 49 26 49 19 31 25 31 18 approach. > 1.91 years 35 23 35 12 83 18 83 10 Mann-Whitney 0.579 <0.001 0.404 0.002 (P) 162 PATTERN OF CARE IN PEDIATRIC PATIENTS DIAGNOSED WITH GASTROESOPHAGEAL 161 REFLUX DISEASE OR ACID RELATED CONDITIONS EVALUATION OF GASTROESOPHAGEAL REFLUX (GERD-ARC) 1 2 3 2 2 AND TREATMENT RESPONSE WITH THE 24 HOUR S.P. Nelson ,E.Wu, S. Kothari , E. Yang , P. Atanasov . 1 MULTICHANNEL INTRALUMINAL-pH PROBE IN Feinberg School of Medicine, Northwestern University, 2 3 CHILDREN WITH ASTHMA Chicago, IL; Analysis Group, Boston, MA; TAP Gabriela Donato1, Marina Orsi1, Judith Cohen Sabban1, Pharmaceutical Pdts Inc, Lake Forest, IL. Alejandro Tepper2, Viviana Rodriguez2, Daniel D Agostino1. 1Pediatric Gastroenterology Unit, Hospital Italiano, Buenos Objective: Identify pattern of diagnosis and treatment of Aires, Argentina; 2Respiratory Unit, Children’s Hospital pediatric GERD-ARC. ‘‘Ricardo Gutierrez’’, Buenos Aires. Methods: Two study samples were identified among patients aged <18 years, diagnosed with GERD-ARC (ICD-9-CM: Background: Children with asthma may have undiagnosed 530.81, 530.1x, 535.xx, 787.1, 789.06), in a proprietary insured gastroesophageal reflux. The Multichannel Intraluminal Impe- claims database (1999–2005). One sample was used to examine dance-pH Probe (MII-pH) is a good method to establish correct physician specialties that diagnosed GERD-ARC and the use of diagnosis and evaluate response to treatment. H2RAs and PPIs around the initial GERD-ARC diagnosis. The

Abstract 161 Table Score pH N acid events N non-acid events Symptom index

X (range) X (SD) X (SD) Cough

Diagnosis (n: 18) 32,6 (2,6–105) 35,11 (19,49) 16,22 (18,24) 38,9 (0–83,3) PPI (n:15) 4,8 (1–14,1) 21,62 (26) 29,73 (19,88) 30,69 (0–73,57) Double dose PPI (n: 4) 5,7 (2,9–9) 18,75 (13,88) 50,5 (43,2) 36,6 (0–93,33)

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E63 index date was defined as the first diagnosis of GERD-ARC. A After controlling for patient baseline costs, patients on PPI still separate sample, with index date as the first prescription of PPI had $115 more GERD-ARC related drug cost (P <.001), but or H2RA, was used to study treatment patterns. Multivariate $188 less GERD-ARC related medical cost (P = .09) and $73 analysis was used to identify factors predicting PPI vs. H2RA as less total GERD-ARC related health care cost (P = .52). The first-line therapy. difference was significant after adjusting for baseline character- Results: The first study sample included 21,471 patients istics. PPI patients incurred $90 more GERD-ARC related drug diagnosed with GERD-ARC by GI specialists (GI-9.2%) or cost (P <.001), $328 less GERD-ARC related medical cost primary care physicians (PCP-90.8%). Patients diagnosed by (P = .004) and $238 less total GERD-ARC related health care GI had more comorbidities and symptoms, and a higher cost (P = .04). prevalence in belching (Relative Risk (RR) = 8.3), dysphagia Conclusion: Although pediatric patients treated with PPI (RR = 6.7), irritability (RR = 7.6), and hematemesis (RR = 8.9), incurred more GERD-ARC related drug costs compared to compared to patients diagnosed by PCP. They were also more patients treated with H2RA, they had lower GERD-ARC related likely to be treated with PPI vs. H2RA. The second study medical and total health care costs after adjusting for baseline sample included 4,729 patients treated with H2RA and 4,600 charateristics. patients treated with PPI. The proportion of patients treated with PPI increased from 31.5% (1999) to 62.6% (2005). 164 Patients on PPI vs. H2RA, had a lower discontinuation rate (1-month RR = 0.7) and a lower switching rate (1-month PSYCHOMETRIC CHARACTERISTICS OF RR = 0.1). The median time on therapy during the first year THE PEDIATRIC GASTROESOPHAGEAL was shorter for patients on H2RA (30 days) than for patients on REFLUX DISEASE SYMPTOM AND QUALITY PPI (60 days). Multivariate analysis showed that older patients OF LIFE QUESTIONNAIRE (PGSQ) 1 2 2 1 with asthma, dysphagia, non-cardiac chest pain were more Smita Kothari , Laurie Roberts , Leah Kleinman . TAP 2 likely to be initiated on PPI. Pharmaceutical Pdts Inc, Lake Forest, IL; Center for Health Conclusion: Most pediatric patients were diagnosed with Outcomes Research, United BioSource Corporation, Bethesda, GERD-ARC by PCP. Those diagnosed by GI were sicker MD. and more likely to be treated with PPI. Over time more patients were treated with PPIs. Introduction: The diagnosis of pediatric gastroesophageal reflux disease (GERD) is usually made by symptom report 163 from a parent or the child or adolescent. Thus, relevant and valid questionnaires assessing symptoms and their impact are import- HEALTH CARE COSTS IN PEDIATRIC PATIENTS ant in evaluating pediatric GERD treatments. The PGSQ was DIAGNOSED WITH GASTROESOPHAGEAL developed using input from patients, parents and physicians, REFLUX DISEASE OR ACID-RELATED and includes items such as ‘‘have a sore throat or burning in CONDITIONS (GERD-ARC) your throat’’ and ‘‘my stomach/chest/throat problems got in the 1 2 3 2 2 S.P. Nelson ,E.Wu, S. Kothari , E. Yang , P. Atanasov . way of my doing school work or school activities.’’ The 1 Feinberg School of Medicine, Northwestern University, objective of this study is to determine the reliability, validity 2 3 Chicago, IL; Analysis Group, Boston, MA; TAP and responsiveness of the PGSQ. Pharmaceutical Pdts Inc, Lake Forest, IL. Methods: Two versions of the PGSQ (parents of children age 2–8 and children aged 9–17) will be evaluated. Seventy Objective: To compare health care costs related to GERD-ARC children with GERD and 40 healthy controls and 110 parents between pediatric patients on H2 receptor antagonists (H2RA) (70 with children with GERD, 40 healthy controls) are being vs. proton pump inhibitors (PPI). enrolled in a 3-week longitudinal study to assess the reliability Methods: Patients (<18 years) with GERD-ARC (ICD-9-CM: and validity of the questionnaires. Internal consistency, test- 530.81, 530.1x, 535.xx, 787.1, 789.06) and initiated on H2RA retest reliability, construct and known group validity and or PPI in 2005 were identified in a claims database. Index date responsiveness will be assessed. Internal consistency reliability was the first prescription of H2RA or PPI. GERD-ARC related is assessed via Cronbach’s alpha. To assess construct validity, costs were compared between groups for 6 months after PGSQ subscales will be compared to the Pediatric Quality of index date. Wilcoxon test compared costs descriptively. Life (PEDsQL) psychosocial and physical subscales. Interim Diff-in-diff analysis controlled for patient baseline costs analyses are presented. (6 months before index date). Regression model adjusted for Results: The PGSQ contains two total domain scores—symp- baseline characteristics (demographics, comorbidities and tom and health-related quality of life (HRQL). Internal con- symptoms). sistency reliability as measured by Cronbach’s alpha was 0.90 Results: The sample included 1,010 patients initiated on H2RA for the symptom score and 0.96 for the HRQL score for children (39%) or PPI (61%). PPI vs. H2RA patients were older (10.8 vs. and 0.93 and 0.88 for parents, respectively. Correlations 9.1 years, P <.001), had 10% more females (P = .002), and a between the children version ranged from 0.66 (PGSQ symp- higher prevalence in dysphagia (Relative Risk (RR) = 2.9), con- tom)-0.83 (PGSQ HRQL) and 0.50 and 0.59 (parent’s version) stipation (RR = 2.8), and vomiting (RR = 2.1). Wilcoxon test for the PEDsQL psychosocial scale. showed that PPI patients incurred $115 more GERD-ARC related Conclusion: The PGSQ total scores demonstrate good psycho- drug cost (P <.001), $175 more GERD-ARC related medical metric characteristics. These two newly developed instruments cost (P = .6), and $290 more total GERD-ARC related health may serve as valid tools for the measurement of symptoms and care cost (P <.001), during the 6 mo after therapy initiation. quality of life associated with pediatric GERD.

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165 Background: Visible changes in the subepithelial vascular pattern (SVP) of the esophagus, seen with white light endo- EFFECT OF ESOMEPRAZOLE ON ACID REFLUX, scopy (WLE) in a gently distended lumen and enhanced by VOLUME REFLUX, AND REFLUX SYMPTOMS IN narrow band imaging (NBI) may be a reliable indicator of NEONATES WITH GASTROESOPHAGEAL REFLUX epithelial disease. The primary aim of this study was to assess DISEASE the relationship between normal or diminished SVP in the Taher Omari1, Geoffrey Davidson1, Ross Haslam2, Patrik 3 3 3 1 esophagus and histologic findings of esophagitis. Bondarov , Emma Naucle´r , Per Lundborg . Gastroenterology Methods: Both WLE and NBI were performed by a single Unit, 2Department of Neonatology, WCH, Adelaide, SA, 3 endoscopist in patients undergoing diagnostic EGD using Australia; AstraZeneca R&D, Mo¨lndal, Sweden. Olympus 180 series equipment. Normal or abnormal SVP was noted at the time of the examination. Routine biopsies Introduction: Proton pump inhibitor therapy reduces acid were obtained from the distal esophagus in all patients, and gastroesophageal reflux (GER) in infants [1]; however, there from the mid or proximal esophagus in the majority. All are few data showing improvement of commonly occurring biopsies were reviewed by a single pathologist blinded to reflux symptoms. patient history and gross findings. Histology was graded for Methods: 25 preterm and term neonates (mean gestational age maximum eosinophils per high power field (0 = none, 1 = 1, 32 wk [95% confidence interval, CI, 23–41]) with reflux 2=2–10, 3 = 11–20, 4 = >20), % total thickness basal zone symptoms received oral esomeprazole 0.5mg/kg once daily hyperplasia (BZH) (0 = none, 1 = 10–25%, 2 = 25–50%, for 7 d. Pts underwent 24-h esophageal pH monitoring alone 3=>50%), and intercellular edema (). (n = 5) or combined with impedance (n = 20). In this post-hoc Results: 14 patients (6 male: 2–17 yr; median = 12 yrs (IQR:9, analysis, pts with reflux index (RI, % time esophageal pH < 4) 15)) were studied. Clinical indications for endoscopy included >11% (>95th percentile for normal infants 3.5 mo [2]) were chronic vomiting or regurgitation (8), dysphagia (6), treated defined as having abnormal acid exposure. Standard impe- esophagitis (4), suspected celiac disease (1), and abdominal dance-based criteria were used to define no. of GER episodes, pain (2). 8 patients were assessed to have absent SVP. Patients proximal extent of reflux (PX GER) and bolus clearance time with normal SVP were more likely to receive histological (BCT GER). Vomiting, gagging, back arching and irritability/ grades of 0 or 1 compared with patients with absent SVP, crying episodes were recorded. (P = .031), and to have fewer eosinophils/hpf (mean = 0.33 Results: Overall, esomeprazole therapy reduced RI (mean (.8) vs 18.63 (16), P <.000). Patients with normal SVP [95% CI] 15.7% [12.7–18.8] at baseline vs 7.1% [4–10.1] on were also less likely to have BZH (mean score 0.83 (.75) vs day 7, P <.0001) but did not alter no. GER episodes (median 2.1 (.83)), and edema (50% vs 87.5%), although these differ- [range] 103 [62–187] vs 88 [63–175]), PX GER (mean [95% CI] ences were not statistically significant. NBI detected distal 8.6 cm [7.8–9.4] vs 9.2 cm [8.4–10]) or BCT GER (mean esophageal islands of columnar mucosa not seen by WLE in [95% CI] 9.9 s [7.4–12.3] vs 9.6 s [7.2–12]). Esomeprazole one patient and confirmed WLE findings of SVP in the significantly improved symptoms in pts with abnormal RI remainder (k = 1.0, P <.000). (Table). Conclusions: This study suggests that absence of SVP on WLE Conclusions: Esomeprazole reduces RI, but does not alter or NBI may be significantly related to esophagitis. Conversely, volume of reflux. Infants with abnormal esophageal acid a normal SVP signifies a low likelihood of high grade eosino- exposure show symptomatic improvement with esomeprazole. philic infiltrate. References: [1] Omari et al. J Pediatr Gastroenterol Nutr 2007;44:41–4. [2] Vandenplas et al. Pediatrics 1991;88:834–40. 167 CONSERVATION OF FEEDING MILESTONES AFTER Equivocal acid exposure Abnormal acid PRIMARY REPAIR OF LONG-GAP ESOPHAGEAL (RI >5% and exposure (RI >11%, ATRESIA Median 11%, n = 8) n = 17) Jeffrey C. Eickhoff1, John E. Foker2, Tara C. Kendall2, (range) no. Khalid M. Khan1. 1Pediatrics, 2Surgery, University of of episodes Baseline Day 7 Baseline Day 7 Minnesota, Minneapolis. Vomiting 3.5 (0–9) 1.5 (0–10) 1 (0–10) 1 (0–3) Gagging 0 (0–7) 0.5 (0–4) 2 (0–12) 0 (0–3) Delayed feeding has been reported in children with esophageal Back arching 1 (0–8) 1.5 (0–12) 1 (0–18) 0 (0–5) atresia and tracheoesophageal fistula (EA-TEF) when primary Irritability/crying 9 (3–23) 8 (5–27) 10 (5–35) 6 (0–28) repair is delayed. At our center the majority of EA are ‘‘long- gap’’ (LG) cases referred at varying ages. Traction applied to P <.05; P <.005 vs baseline (Wilcoxon signed rank test). esophageal remnants is used to achieve primary repair. We examined effects of delayed oral feeding on completion of feeding milestones. A questionnaire based on the Denver II 166 development chart was used to compare children who underwent long-gap EA repair (LG-EA), n = 32, gap of >2.5cm, to VASCULAR PATTERNS, NARROW BAND IMAGING, the typical short-gap EA-TEF, gap 2.5cm (SG-EA), n = 9, and AND ESOPHAGITIS to a control (C) population of children, n = 26. The comparisons Victor L. Fox, Jenifer R. Lightdale, Lisa B. Mahoney, were from birth for C and 4 weeks after operative repair for EA. Jonathan Glickman. Children’s Hospital Boston, Boston, MA. Factors investigated were traction, cervical spit fistula,

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E65 gestation and age at repair. Feeding with finger foods was Conclusions: Endoscopically suspected BE is rare in children achieved at 15.2 (12.8) months in the LG-EA group compared and adolescents (14/1000). Intestinal metaplasia in these areas to 8.1 (4.3) months and 10.8 (4.6) months in the SG-EA and is unusual (overall 1.31/1000). These preliminary results C groups, respectively, P = 0.092. Eating solids with a spoon/ suggest that vigorous standardization for the identification fork occurred at 22.0 (14.6) months, 14.3 (3.0) months and and recording of endoscopic landmarks does not appreciably 19.6 (7.8) months in the same respective groups, P = 0.324 alter recent retrospective prevalence estimates of BE in chil- and drinking from an adult cup and retaining all liquids dren. occurred at 21.22 (15.0) months, 12.4 (14.6) months and 18.5 (7.8) months, respectively, P = 0.385. Major feeding 169 milestones were completed at 26.4 (9.4) months in the LG-EA, 22.9 (0.1) months in the SG-EA, and 27.5 (7.5) PSYCHOLOGICAL AND BEHAVIORAL months in the C population, P = 0.743. Feeding milestones for CHARACTERISTICS OF ADOLESCENT the EA group requiring traction, 20/32 of the long gaps, PATIENTS PRESENTING FOR BARIATRIC SURGERY 1 1 1 versus non-traction and controls, were similar to those for Francine Samuels , Jeffrey Zitsman , Mary Ann Witt , Timothy 2 2 2 long and short gaps and controls. There was no correlation Walsh , Michael Devlin , Ana Diaz Zubieta , Elizabeth B. 2 1 between gestational age and age at repair to major feeding Finkelson . Pediatric GI/Hepatology, Morgan Stanley milestones in the EA population. Completion of major feed- Children’s Hospital of NY Presbyterian Columbia Medical 2 ing milestones was similar between EA patients and controls Center, New York, NY; NYS Psych Institute Columbia although individual elements varied significantly. Spit fistulas University, New York, NY. benefit early transition to independent feeding. The application of traction and long-gaps did not delay completion of The primary objective of the study is to examine psychological feeding milestones. and behavioral symptoms in a sample of morbidly obese adolescents before and after undergoing laparoscopic adjustable 168 gastric banding (the Lap-Band system). Current data are available from the initial evaluation of 14 participants. Participants THE PREVALENCE OF BARRETT’S ESOPHAGUS and their parents or guardians were evaluated by a psychiatrist IN CHILDREN: A PROSPECTIVE MULTI-CENTER preoperatively. Participants completed structured measures STUDY including the PedsQL (a pediatric measure of health-related 1 4 2 Mark A. Gilger , Hashem B. El-Serag , Mitchell Shub , quality of life), the Beck Depression Inventory (BDI), the 3 1 1 Mark Integlia , Nina Tatevian , Milton Finegold , Amy Rosenberg Self Esteem Scale (RSE), and the Questionnaire 2 3 1 1 4 Joswiak , Tim Messitt , Kenn Fairly . Pediatrics, Medicine, on Eating and Weight Patterns-Revised (QEWP-R) (a 28-item 2 Baylor College of Medicine, Houston, TX; Pediatrics, Phoenix self-report questionnaire that assesses the presence of Binge 3 Children’s Hospital, Phoenix, AZ; Pediatrics, Barbara Bush Eating Disorder). Parents completed the parent-proxy PedsQL Children Hospital, Portland, ME. and the Child Behavior Checklist (CBCL). Participants were between 13–17 years of age (mean, 15.64 1.28 yrs) with a Background: The prevalence of BE in children is unclear. In a mean BMI = 48.71 10.9 kg/m2. Sixty-four percent of the previous retrospective cross-sectional study of suspected BE in participants were female. Fifty percent were Hispanic, 28% children we identified 6731 who underwent esophagogastro- Non-Hispanic White, 14% Non-Hispanic Black, and 1% half duodenoscopy (EGD). 17 had suspected BE (prevalence, Hispanic and half Non-Hispanic Black. The mean BDI was 2.5/1000). Intestinal metaplasia was reported in 9/17(53%). 15.98 8.54, within the mild to moderate depression range but Older age and hiatus hernia were risk factors for BE. a mean RSE in the normal range (25.4 1.56). Participants Purpose: To estimate the prevalence of BE in children exhibited quality of life scores that were significantly lower undergoing EGD. than published norms for healthy children and adolescents. Methods: A prospective, multi-center study using PEDS-CORI 35% of participants reported a history of binge eating on the including all children 0 to 18 years undergoing EGD. Thera- QEWP-R. 23% met criteria for Major Depressive Disorder, peutic endoscopies were excluded. Endoscopic procedures were 23% for dysthymic disorder, and 15% for anxiety disorder. One standardized by (1) measuring the distance from the upper patient’s psychiatric evaluation was not completed secondary incisor to the Z-line & to the proximal lesion, (2) determining to a significant suicidal ideation necessitating immediate the Los Angeles Classification of esophageal erosions, (3) evaluation in the emergency department. These data, though photographing the lesion and the gastroesophageal junction. preliminary and limited by a small sample size, are similar to Biopsies were obtained from suspected BE areas & evaluated by those recently reported and indicate that significant psychoso- two pathologists. BE was defined as the presence of goblets cial impairment is common among morbidly obese adolescents cells characteristic of intestinal metaplasia. presenting for weight-loss surgery. Results: 66% of children undergoing EGD agreed to participate. To date, 759 children aged 9.9 4.9 have been enrolled. 170 Only 1.5% had cerebral palsy and 4.3% had mental retardation. The main complaints were heartburn (27%), regurgitation ESOPHAGEAL CAPSULE ENDOSCOPY IN YOUNG (30%), vomiting (37%), and poor weight gain (29%); multiple PATIENTS WITH PORTAL HYPERTENSION complaints may have been present in the same person. Eleven Victor L. Fox, Adrienne Scheich, Jenifer R. Lightdale. cases of suspected BE have been identified (11/759 = 14/1000). Gastroenterology and Nutrition, Children’s Hospital Boston, One case of suspected BE had intestinal metaplasia (1/759). Boston, MA.

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Background: Patients with portal hypertension (HTN) and (n = 1), prematurity (n = 1), short bowel syndrome (n = 1), devel- varices are at risk for spontaneous life-threatening bleeding. opmental delay (n = 2). Fistulae were present for 3 to 10 months Initial studies of esophageal capsule endoscopy (ECE) in adults prior to closure, and drainage caused either skin breakdown or have shown excellent sensitivity for detecting varices to guide social difficulty in all cases. Endoscopic closure consisted of therapy. ECE has not been reported in children. We reviewed application of silver nitrate externally to the fistula tract after our initial experience with ECE in a cohort of young patients general anesthesia was induced. Standard upper endoscopy with portal HTN at a pediatric referral center. identified the luminal side of the fistula, and electrocautery Methods: Beginning in October 2005, patients with evidence of was applied to the tract using a Gold Probe at 15 Watts to induce cirrhosis or portal HTN and able to swallow pills were offered scar formation. Subsequently 3 or 4 endoclips were applied ECE using the Pillcam ESO device (Given Imaging) to detect endoscopically to seal the tract on the gastric side. varices. A modified ingestion protocol with overnight fasting Results: All patients tolerated the procedure well, and there and real-time viewing was used to attempt complete UGI were no complications. All were discharged on the day of the endoscopy. procedure on their baseline diets. There has been no further Results: A total of 28 procedures (21 primary screening, 7 post- gastrostomy drainage on follow-up ranging from 3 weeks to treatment surveillance) were conducted in 27 patients 6 months. (19 male): 21 were <18 yr of age (mean = 13 yr, range 9– Conclusions: Endoscopic gastrocutaneous fistula closure using 17), 6 were >18 yr (mean = 20 yr, range 18–25). Primary electrocautery and endoclips is a safe and effective outpatient diagnoses included cystic fibrosis (8), extrahepatic portal vein procedure in pediatric patients, and should be seriously con- obstruction(5), non-alcoholic steatohepatitis (3), biliary atresia sidered as an alternative to traditional surgical closure when (2), alpha-1 antitrypsin deficiency (2), complex congenital heart medical management has failed. disease (2), and other (5). Esophageal studies were complete in 27 of 28 studies. Mean esophageal recording time = 192 sec 172 (range 4–631); total recording time = 20 min. One study was aborted due to an uncooperative patient. Esophageal varices DOES SWALLOWING PLAY A ROLE IN THE were small in 10(37%), medium to large in 4 (17%), and not CLEARANCE OF ‘‘pH ONLY’’ ACID detected in 13 (48%) patients. Other esophageal findings GASTROESOPHAGEAL REFLUX EVENTS IN included esophagitis (5), heterotopic columnar epithelium INFANTS? (4), yeast (2), and stricture (1). Gastric varices were seen in Roberto A. Gomez, Frederick Woodley, Carlo Di Lorenzo, John 10 (37%). Duodenal imaging was achieved in 7 studies and Hayes, Hayat Mousa. Pediatric Gastroenterology, Columbus revealed erosions (3), varices (1), and normal (3) findings. Children’s Hospital, Columbus, OH. Complications were limited to transient esophageal retention in one patient with a history of a distal stricture. Background: ‘‘pH only’’ events (POEs) are acid gastroeso- Conclusion: ECE may be a feasible alternative to conventional phageal reflux (AGER) episodes that are detectable by esopha- endoscopy for screening and surveillance of esophageal varices geal pH monitoring (EPM) but not by multichannel intraluminal in cooperative children. Further modifications of equipment and impedance (MII). MII/EPM events are AGER episodes that are technique are needed to optimize complete UGI imaging. detectable by both EPM and MII. Swallowing is known to be important for the volume clearance and chemical clearance of 171 MII/EPM events whose intraluminal flow is detectable by MII. For POEs, whose intraluminal status remains unclear, the role of ENDOSCOPIC CLOSURE OF GASTROCUTANEOUS swallowing for clearance has not been reported. FISTULAE USING ELECTROCAUTERY AND Objective: To compare the frequencies of swallowing in ENDOCLIPS response to MII/EPMs and POEs. Bradley A. Barth. University of Texas Southwestern Medical Methods: MII/pH tracings from 14 infants (median age, Center-Children’s Medical Center of Dallas, Dallas. 14 wks) were examined over the course of four feeding cycles. For both event types, we calculated mean numbers of swallows Background: Persistent gastrocutaneous fistula after elective (sw/min) during: 1) the 5 min period before esophageal acid- removal of gastrostomy tube is a common complication in ification, 2) the period during acidification, and 3) the 5 min pediatric patients. Standard therapy for gastrocutaneous fistulae period following neutralization. Results: 336 total AGER events involves laparotomy and surgical excision of fistula tract. were detected; 122 were POEs and 214 were MII/EPMs. 4607 Endoclips are metal devices that can be easily applied to the total swallows were detected. The overall number of swallows GI mucosa through standard flexible endoscopes. Teitelbaum per minute was not different (P = .09) between MII/EPMs (1.12 et al reported endoscopic closure of chronic gastrocutaneous sw\min, 1.01–1.24, 95%CI) and POEs (1.02 sw\min, 0.9–1.09, fistulae in 3 pediatric patients in 2005. This series reports 95% CI). For MII/EPM and POE events, respectively, the 4 additional pediatric cases of persistent gastrocutaneous mean frequencies were: 1) 0.91 sw/min (0.45–1.09, 95% CI) fistulae, successfully closed using a technically simple, mini- and 0.87 sw/min (0.68–1.09, 95% CI) before esophageal acid- mally invasive outpatient procedure involving electrocautery ification (P = .99), 2) 1.45 sw/min (1.24–1.69, 95% CI) and and endoscopic clipping. 1.25 sw/min (1.02–1.69, 95% CI) during acidification (P = .55), Patients and Methods: Four children age 2 to 7 years (10– and 3) 1.04 sw/min (0.87–1.24, 95% CI) and 0.96 sw/min 25 kg) underwent endoscopic closure of gastrocutaneous fistula. (0.76–1.24, 95% CI) following neutralization (P = .96). The Gastrostomy tubes had been placed due to inadequate interaction between period and event type was not significant caloric intake associated with tracheoesophageal fistula (P = .66).

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Conclusions: There were no significant differences in the Rapamycin (marketed as Sirolimus), a potent immunosuppres- frequency of swallowing in response to either POEs or MII/ sant is currently administered as a long-term regiment to EPMs (before, during, or after). Similarity in swallowing prevent rejection episodes in organ transplantation. Rapamycin frequency between the two AGER event types suggests that exerts its effect by inhibiting the mammalian target of swallowing may play an important role for clearance of POEs in rapamycin (mTOR) a central regulator of cellular growth and infants. It is unclear whether this role is for volume clearance, development. Because of its inhibitory effect on cellular growth, chemical clearance,or both. rapamycin is also used in cancer therapy. Consequence of chronic exposure to rapamycin on growth and development 173 in children is not known. We have injected newborn mice with 0.5 mg/kg at P2 and P14 (day of life) and examined their PRENATAL EXPOSURE TO METHAMPHETAMINE body and liver growth. Mice that received rapamycin were PRESENTING AS NEONATAL CHOLESTASIS 30% smaller than control at P30. Liver in these mice was also Ahmed Dahshan. Ped GI & Nutrition, Oklahoma University, smaller than control (20% of control at P30). Measuring cell Tulsa. size in liver sections showed that a reduction in the size of hepatocytes (30% of control at P30) underlies the reduction in Introduction: Methamphetamine (meth) has been recognized liver weight. Examination of liver function in the rapamycin- as a common cause of acute toxic hepatitis in adults with treated mice revealed a pronounced increase in the levels of clinical and histological features indistinguishable from acute liver enzyme including transaminases, AP, bilirubin and LDH. viral hepatitis. Clinical presentation of meth hepatotoxicity In conclusion, these data suggest serious side effects of rapa- variable from mild acute hepatitis with prompt recovery to mycin use in pediatrics including inhibition of normal body and fulminant hepatic failure. The pathophysiology of this hepato- liver growth. toxicity is not well elucidated. Prenatal exposure to meth has been linked to intrauterine growth retardation and variety of 175 withdrawal symptoms. Neonatal cholesatasis is rare but serious problem that indicates hepatobiliary dysfunction and has CLINICAL ASPECTS AND VPS33B MUTATIONS IN several etiologies. These include infectious, metabolic, endo- PATIENTS WITH ARC SYNDROME 1 1 1,2 crine, toxic, structural, familial and autoimmune disorders. Joo Young Jang , Kyung Mo Kim , Han-Wook Yoo , 1 3 1 2 Cholestatic hepatitis is a recognized complication of exposure Young Seo Park , Eunsil You . Pediatrics, Medical Genetics, 3 to some drugs including carbamazepine and trimethoprim- Pathology, Asan Medical Center, Seoul, South Korea. sulfamethoxazole. Case: A 35 week preterm, appropriate for gestational age, Objectives: ARC (Arthrogryposis, renal dysfunction, and Caucasian girl was born to a 39 years old mother who had cholestasis) syndrome is a rare, fatal cause of neonatal no prenatal care. The mother’s urine drug screen revealed meth. intrahepatic cholestasis without known treatment modalities The baby passed pale meconium and her subsequent stools were which recently ascribed to a mutation in the VPS33B gene. hypo-pigmented. A detailed work up was done and was We have assessed the clinical aspects and investigated unremarkable except for hepatobiliary scintigraphy, which the VPS33B mutations in Korean patients with ARC syn- showed no activity in the small bowel on delayed imaging. drome. An operative cholangiogram and liver biopsy were performed. Methods: We reviewed the medical records of 6 patients with The cholangiogram revealed patent bile ducts. The biopsy was ARC syndrome among 90 patients with neonatal cholestasis consistent with acute viral or toxic hepatitis. Gradual drop of from 2000 to 2005 and assessed the relative incidence rate ratio, bilirubin was noted. With negative extensive work up for other their clinical symptoms, laboratory, and pathologic findings. etiology, known hepatotxicity of meth, early onset of cholestasis DNA of 5 patients, 4 parents and 1 fetus was analyzed for which improved without specific therapy, it is strongly sus- VPS33B mutations. pected that prenatal exposure to meth is the most likely culprit. Results: The relative incidence rate ratio was one seventh of Discussion: This is the first recorded case of neonatal choles- biliary atresia (95% CI 0.33–0.06). All 6 patients presented tasis related to prenatal exposure to meth. Meth is considered with ichthyosis, recurrent infection, and failed to thrive with the the fastest-growing illicit drug in the US. Hence, prenatal 3 main symptoms (arthrogryposis, renal dysfunction, and cho- exposure to meth is expected to rise. Healthcare providers lestasis). All died by the age of 12 mos. They had various should become aware of the possibility of methamphetamine severities of cholestasis and metabolic acidosis, and some effect on the fetal liver. Raising awareness of the expectant patients had nephrogenic diabetes insipidus, chronic diarrhea, mothers through the healthcare profession may reduce the risk platelet abnormalities, bleeding tendency, and central nervous of this condition. system anomalies. We identified a novel c.403+2T>A splice site mutation, 2 frame shift mutations (c.1509_1510insG, 174 c.790_791del), 1 nonsense mutation (c.661C>A), and 1 known nonsense mutation (c.1518C>T) in the VPS33B gene. One LIVER DEFICIT IN NEWBORN MICE TREATED WITH fetus was found to be a mutation carrier, with the c.1518C>T RAPAMYCIN mutation from the father. Girish C. Sharma1, Stuart Berezin1, Leonard J. Newman1, Conclusions: This study suggested that the incidence of ARC Reza Farahani2. 1Pediatrics Gastroenterology, 2Basic Science/ syndrome is not so rare. We found 4 novel and one known Microbiology, New York Medical College/Westchester Medical mutations in ARC syndrome patients which will facilitate Center, Valhalla, NY. genetic diagnosis and counseling for affected families.

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176 Purpose: To characterize liver function abnormalities in children who present with ALL and examine their impact on PROXIMAL GASTROINTESTINAL PATHOLOGY treatment and outcome. IN CHILDREN WITH HYPOFUNCTIONING Patients and Methods: The Oncology Database at BC Chil- GALLBLADDER dren’s Hospital was searched for new cases of ALL between Wikrom W. Karnsakul1, Kathryn Skitarelic2, Stacey Gillespie1, 3 4 1 2001 and 2006. Hepatic biochemistries, other investigations, Tarun Kumar , Gary Marano . Pediatrics, Robert C. Byrd induction therapy and outcome were recorded. Health Sciences Center, West Virginia University School of 2 3 4 Results: 147 patients were identified—83% with B-cell ALL. Medicine, Morgantown; Pathology, Surgery, Nuclear 34% of the patients had abnormal transaminases. Of Medicine, West Virginia University School of Medicine. 41 patients with abnormal AST, 39% were >2xULN. Of 29 patients with abnormal ALT, 52% were > 2xULN. 25% Background: Children with right upper quadrant abdominal of B-cell and 63% of T-cell ALL patients had hepatitis at pain often are diagnosed with hypofunctioning gallbladder presentation. None had fulminant liver failure. Two patients (GB) during cholescintigraphy (HIDA) by assessing GB underwent liver biopsy: one demonstrated interface hepatitis emptying with cholecystokinin (CCK) stimulation. GB ejection and blast infiltration; the other showed giant cell hepatitis. All fraction < 35% is considered a hypofunctioning GB. A referral patients with only transaminasemia received standard therapy. for gastrointestinal (GI) consultation often leads to an upper 3 of 4 patients with conjugated hyperbilirubinemia received endoscopy (EGD) to exclude GI pathology prior to surgical steroids for 4–7 days prior to full dose induction therapy. evaluation. There was no delay in initiation of consolidation therapy in the Objective: To assess proximal GI pathology in children with patients, implying no untoward events with the induction hypofunctioning GB. protocol. Method: From May 2004 to May 2007, a retrospective medical Conclusion: Abnormalities in hepatic transaminases are com- record review was performed in 16 children with right upper mon with ALL at presentation; conjugated hyperbilirubinemia quadrant (RUQ) pain who required HIDA at West Virginia is unusual. Patients with jaundice had marked response to University Hospitals. All with decreased GB function under- pretreatment steroid therapy. Whether there is a need to delay went an EGD. GI histologic findings were reviewed in each or modify the induction protocol in this setting requires further child. study. Results: 16 children (7.5–18 y) presented with RUQ pain (100%), food intolerance (93%), emesis (80%). Seven patients 178 had cholecystectomy and continued to have persistent GI symptoms after surgery. GB pathology from all showed mild INTERPRETING CONJUGATED BILIRUBIN LEVELS chronic cholecystitis. Histologic reports from EGD include IN INFANCY reflux esophagitis (13 children), lymphocytic esophagitis (1), Adam R. Davis1, Phil Rosenthal1, Gabriel Escobar2, Thomas chronic non-atrophic gastritis (7), lymphoid aggregates in Newman1,2. 1Peds, University of California-San Francisco; antrum (3), increased eosinophilic infiltrations in duodenum 2DOR, Kaiser Permanente, Oakland, CA. (1), and increased intraepithelial lymphocytes (1). All children had clinical symptoms related to functional GI disorders. Four Background: Conjugated (CB) and direct-reacting bilirubin had a change of GB ejection fraction after medical treatment levels (DB) are often measured to evaluate hepatobilliary with antireflux medication and/or tricyclic antidepressant. function. No previous study has evaluated a large community Conclusion: Although abnormal proximal GI pathology is not population of U.S. infants to define and determine the clinical uncommon in children with hypofunctioning GB in our series, it significance of elevated levels. may not be cost-effective to perform an EGD without definite Aims: 1) To compare the distribution of CB vs. DB in the 1st indications. Cholecystectomy is an ineffective therapy for two weeks of life 2) To evaluate the incidence of cholestatic hypofunctioning GB in those with history consistent with disease in infancy 3) To describe the positive predictive value of functional GI disorders. CB for various diseases in infancy. Methods: Retrospective cohort study of 271,186 infants born 177 within a Northern California hospital network from 1995– 2004. 65,689 had at least one CB measured. Inpatient and ABNORMAL HEPATIC BIOCHEMISTRIES AT outpatient ICD-9 codes were obtained. PRESENTATION OF ACUTE LYMPHOBLASTIC Results: CB was usually undetectable (89%); DB levels were LEUKEMIA OF CHILDHOOD: IMPACT ON significantly higher (Table 1). During infancy, 9.2/10,000 had a INDUCTION THERAPY AND OUTCOME CB 2.0mg/dL, 6.7 were diagnosed with liver disease, 4.3 1 2 2 Idit Segal , Rod Rassekh , Mason Bond , Richard A. with biliary disease and 1.2 with biliary atresia. Table 2 1 1 2 Schreiber . Pediatrics-GI Division, Pediatrics-Hematology summarizes the distribution of diagnostic categories at various Oncology, British Columbia Children’s Hospital, Vancouver. CB levels. Conclusions: CB and DB measurements cannot be interpreted Introduction: Acute lymphoblastic leukemia (ALL) is the most interchangeably. Even mildly elevated CB is abnormal. With common malignancy in childhood. While hepatic compli- levels 0.5 mg/dL and <2.0 mg/dL, infection must be ruled out cations associated with the treatment of ALL are widely and the infant should be followed over time. With levels recognized, few reports have described the spectrum of liver 2.0 mg/dL, a more in-depth assessment of the hepatobilliary involvement in ALL patients at diagnosis. system should be considered.

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TABLE 1. Distribution of Maximum CB vs. Maximum DB in TABLE 1. First 2 Weeks of Life Patient 1 Patient 2 Patient 3 Percentile Age/gender 4 day/F 22 mo/M 3 yo/M Serum concentration Clinical presentation 32-wk Jaundice, Jaundice, (mg/dL) Conjugated (N = 53,397) Direct (N = 2,898) prematurity, emesis, fever, 0.0 89% 0.03% shock fever diarrhea 0.3 97.5% 61% Isolation of enterovirus Plasma PCR, Plasma PCR Stool PCR 1.0 99.8% 97% Urine cx, 2.0 99.93% 98.8% NP/optic cx, liver tissue cx Liver pathology Massive necrosis Submassive Submassive necrosis necrosis TABLE 2. Relation Between Maximum CB Level and ICD-9 Outcomes Death Successful Normalization Diagnoses liver of liver transplant function, Conj bili Conj bili Conj bili aplastic (mg/dL) 0.5–1.9 (mg/dL) 2.0–4.9 (mg/dL) 5.0 anemia (N = 4535) (N = 167) (N = 73)

Diagnostic Diagnostic Diagnostic 180 Categories % Categories % Categories % JUVENILE HEMOCHROMATOSIS IN A 7-YEAR-OLD No ICD-9 diagnosis 88 No ICD-9 53 Biliary disorder 47 BOY SECONDARY TO A NOVEL HEMOJUVELIN diagnosis MUTATION Severe bacterial 2 Liver disease 21 Liver disease 43 infection Kyle Kusek, Mark Ranalli, Bonita Fung, Carol Potter. GI abnormality 1 Biliary disorder 10 GI abnormality 27 Columbus Children’s Hospital, Columbus, OH. Liver disease 0.3 GI abnormality 10 No ICD-9 21 diagnosis Hereditary hemochromatosis results from increased dietary iron Biliary disorder 0.2 Severe bacterial 10 Severe bacterial 18 absorption and progressive iron overload. Affected adults with infection infection type I hemochromatosis have mutations in the HFE gene and can develop liver, heart, pancreas, and pituitary disease, usually 179 after 40 years of age. Juvenile (type II) hemochromatosis presents in childhood with similar involvement and results from PEDIATRIC ENTEROVIRUS INFECTION AND mutations in the HAMP and HJV genes. HAMP encodes the FULMINANT HEPATIC FAILURE hepcidin protein which appears to downregulate intestinal iron 1 1 2 1 Meghan M. Trojnar , D. Shores , C. Zuppan , M. Klooster ,G. absorption. HJV encodes the hemojuvelin protein which is 1 1 1 Yanni , M. Shah . Department of Pediatric Gastroenterology; thought to modulate hepcidin expression. We report the case 2 Department of Pathology, Loma Linda University Medical of a 7 year-old asymptomatic male who presented to our clinic Center and Children’s Hospital, Loma Linda, CA. with hard hepatomegaly, splenomegaly, and apparent cirrhosis. Liver enzymes showed modest elevation with ALT 197 U/L, Background: Enterovirus infection is a rare cause of FHF. AST 283 U/L, and GGTP 89 U/L. Bilirubin and PT were Neonates are particularly at risk, but it may affect older normal. Ultrasound showed splenomegaly, a large left liver children. Enterovirus infection may be difficult to diagnose, lobe, a shrunken right liver lobe, and normal blood flow. He had but can be detected in serum, stool, and urine. In general, it moderate hypersplenism with WBC 3500/mm3, Hgb 13.9 g/dL, follows a benign course with spontaneous recovery in the and platelets of 110,000/mm3. Laboratory evaluation for alpha- majority of cases. The development of FHF following enter- 1 antitrypsin deficiency, cystic fibrosis, Wilson’s disease, auto- ovirus infection has been described only in case series. immune disease, and infectious hepatitis was unremarkable. Aim: Review of three children diagnosed with Fulminant Liver biopsy demonstrated severe bridging fibrosis and iron Hepatic Failure (FHF) secondary to enterovirus infection. content of 19,635 mg/g dry weight. Iron studies showed serum Methods: Retrospective chart review of children admitted with iron of 222 mg/dL, TIBC 280 mg/dL, transferrin saturation 79%, FHF secondary to enterovirus infection. and ferritin 1,323 mg/mL. Genetic testing was negative for Results: See Table 1 HFE and HAMP mutations but showed two separate missense Conclusions: 1. Enterovirus infection should be considered in mutations of the HJV gene—the well known G320V mutation the work up of FHF in neonates and older children. 2. andanunreportedR92Pmutationonexon3.Withregular Enterovirus infection may be difficult to diagnose, so samples phlebotomy his iron studies have improved with serum of serum, stool, and urine should be sent for PCR and/or iron 171 mg/dL, TIBC 293 mg/dL, transferrin saturation culture once FHF is diagnosed. 3. Enterovirus FHF is charac- 58%, and ferritin 80 mg/mL. Repeat liver biopsy one year terized by severe coagulopathy and massive hepatic cellular after presentation showed continued bridging fibrosis and necrosis. 4. Children with FHF secondary to enterovirus iron content of 3032 mg/g. He has continued with good infection should be referred early for liver transplant evalu- health and growth. Juvenile hemochromatosis can present ation. in early childhood and results from any of a range of genetic

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E70 mutations in either the HAMP or HJV genes. The 2. Janes CH, et al. Outcome of patients hospitalized for com- exact mechanisms of these gene products remain to be plication after outpatient liver biopsy. Ann Intern Med characterized. 1993;118:96–98

181 182 IS SHORT OBSERVATION TIME FOLLOWING SUCCESSFUL USE OF THERAPEUTIC PLASMA PERCUTANEOUS LIVER BIOPSY IN CHILDREN EXCHANGE (TPE) AND/OR CONTINUOUS RENAL SAFE? REPLACEMENT THERAPY (CRRT) IN PEDIATRIC Lina Karam. Pediatrics and Communicable Diseases, LIVER FAILURE 1 2 2 2 University of Michigan, Ann Arbor. Darla R. Shores , Peter Yorgin , Drew Cutler , Shobha Sahney , Marquelle Klooster1, Manoj Shah1, George Yanni1. 1Pediatric 2 Background and Aims: Percutaneous liver biopsy is an Gastroenterology, Pediatric Nephrology, Loma Linda important tool in the management of liver disease for establish- University Medical Center, Loma Linda, CA. ing diagnosis, evaluating prognosis, and monitoring the Background: Although the use of TPE and CRRT in pediatric effect of therapy. Complication rates have been reported to 1,2 patients with fulminant liver failure has been described in the range from 0.5%-2.8%. The aim of this study was to deter- literature, patient numbers have been few. Fulminant hepatic mine whether pediatric patients undergoing percutaneous liver failure in the pediatric population has a high mortality and biopsy can be safely discharged home after a short period morbidity, and requires a multidisciplinary approach for man- of observation. agement. International studies in the adult population showed Methods: All children who underwent percutaneous liver that artificial liver support with Molecular Adsorbant Recircu- biopsy at the University of Michigan between October 2002 lating System (MARS), similar mechanism of action to TPE and and December 2006 were evaluated in this study. Liver biopsy CRRT, improves pathophysiologic sequelae and outcome of was performed with a bard monopty needle (16 or 18 g) acute and acute on chronic liver failure. after ultrasound marking. Major complications requiring hospi- Aim: Review of CRRTand or TPE use in Pediatric patients with talization or resulting in death were recorded. Patients were fulminant hepatic failure (FHF) and acute-on-chronic Liver observed overnight if they were 24 mo, those with complex failure (CHF). medical problems and those living 4 hours or more from the Methods: Retrospective chart review of pediatric patients hospital. admitted to LLUCH with FHF who were treated with CRRT Results: 193 percutaneous liver biopsies were performed on and or TPE were reviewed. End point was clinical recovery or 132 patients. There were 3 complications: two patients devel- availability of liver donor. oped intraperitoneal bleeding one of them leading to death Results: See Table. and one patient developed a hemothorax. Two of the com- Conclusion: 1. CRRTand TPE are safe and effective supportive plications developed within the first 10 minutes after the therapy for pediatric patients with FHF or acute-on-chronic procedure while the patients were still in the recovery room. liver failure The third complication presented more than 24 hours after 2. Use of CRRT and or TPE is associated with spontaneous discharge. recovery or improved pre-transplant clinical condition. Conclusions: Major complications after percutaneous liver biopsy in children develop either within the first 1 hour after 183 the procedure or more than 24 hours after discharge. This suggests that an observation period of 4 hours is safe and will ROLE OF BMI IN HCV PROGRESSION IN THE YOUNG help optimizing bed utilization in the outpatient setting. Special Aymin Delgado1,2, Marielle Christofi2, David Healey2,DavidA. considerations need to be given for patients 24 mo of age and Ludwig1, Raymond T. Chung3,4, Maureen M. Jonas2,4. those with risk factors. 1Pediatrics, University of Miami, Miami, FL; 2Medicine/ References: Gastroenterology and Nutrition, Children’s Hospital Boston, 1. Papini E, et al. A randomized trial of ultrasound guided Boston, MA; 3Medicine/Gastroenterology and Hepatology, anterior subcostal liver biopsy versus the conventional Men- Massachusetts General Hospital, Boston; 4Harvard University, ghini technique. J Hepatol 1991;12:291–297 Boston.

Abstract 182 Table Patient 1 Patient 2 Patient 3 Patient 4 Patient 5

Age/gender 18 y/F 22 m/M 17 y/F 12 y/F 16 y/M Clinical presentation FHF FHF FHF CHF FHF Pathology Focal necrosis Acute inﬂammation, Central lobular Portal ﬁbrosis, ductal Acetominophen necrosis congestion/necrosis, proliferation toxicity venular thrombosis Etiology Acetominophen Enterovirus infection Budd-Chiari Syndrome Langerhans cell Acetominophen toxicity histiocytosis toxicity Treatment CRRT, TPE CRRT, TPE CRRT CRRT TPE Outcomes Spontaneous Successful liver Successful liver Successful liver Spontaneous recovery transplant transplant transplant recovery

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Background/Aims: Evidence suggests that obesity plays a role of the clinical files was done to determine if a specific diagnosis in development of fibrosis in hepatitis C (HCV) infected adults. was done. However, the role of obesity in HCV infection of the young has Results: n = 77, 37.7% girls, mean age on admission 93.3 not been previously evaluated, and the determinants of severity of 84 days. 23 (30%) had anatomical diseases (group A) and 54 HCVinfection in pediatrics remain unclear. The aim of this study (70%) were not surgical (group B). In group A 20 (87%) had was to evaluate whether overweight is associated with progres- biliary atresia, 2 (8.7%) choledocal cyst and one (4.3%) a sion to fibrosis among HCV-infected children and adolescents. portahepatis neoplasm. In group B, a specific diagnosis was Methods: All HCV-infected subjects 20 years of age or younger established in 45(83.3%), including multifactorial cholestasis (mean = 14.1, SD = 3.9) followed at CHB between 1998 and (sepsis, TPN and hemolysis), CMV hepatitis, Alagille syndrome, 2007 (n = 92), who had an available biopsy were included. hypotiroidism,galactosemia,toxoplasmosis,Jeunesyndromeand Demographic information, medical histories, liver histology, familial cholestasis. The probability of establishing a specific and anthropometrical measurements at the time of biopsy were diagnosis was 28.7 higher in infants with biliary atresia or cho- analyzed. Subjects’ BMI percentiles and subsequent z scores ledocal cyst than in cases with non-surgical entities (P < 0.001). were calculated from CDC smoothed percentile curves of the Conclusions: Identification of anatomical etiology of NHANES data. Degree of fibrosis and steatosis were quantified cholestasis is a resolved problem with the current diagnostic by a four point scale (none, mild, moderate, severe). protocols. However, differential diagnosis of non-surgical enti- Results: Mean (SE) BMI z scores across the four categories ties continues to be an issue, particularly in emerging GI groups of fibrosis were relatively constant (none = 0.33 0.43, mild = with limited diagnostic resources. 0.27 0.15, moderate = 0.64 0.30, severe = 0.66 0.49). Although the associated P value for the test statistic (ANOVA) was somewhat large (F(3,89) = 1.70, P = 0.1737), if anything, Intestine/Colon/IBD there was a trend towards lower BMI z-scores among patients in the severe fibrosis category. Categorization of subjects was 185 collapsed into presence or absence of steatosis. There was a MURAMYL DIPEPTIDE ACTIVATION OF statistical difference in mean BMI z scores between subjects with NUCLEOTIDE-BINDING OLIGOMERIZATION (0.80 0.23) and without (0.07 0.15) steatosis (F(1,90) = 7.03, DOMAIN 2 AMELIORATES EXPERIMENTAL P = 0.0094). COLITIS THROUGH INDUCTION OF IRF4 Conclusion: No evidence was found to support the hypothesis Ivan J. Fuss1, Tomohiro Watanabe1, Naoki Asano1, that increased BMI is associated with increased fibrosis in Peter Murray2, Keiko Ozato3, Atsushi Kitani1, Warren Strober1. pediatric subjects infected with HCV. However, increased 1Mucosal Immunity Section, 3NICHD, National Institutes of BMI was associated with the presence of steatosis. Childhood Health, Bethesda, MD; 2Department of Infectious Diseases, overweight may indirectly contribute to fibrosis later in life St. Jude Children’s Research Hospital, Memphis, TN. through the development of steatosis. In studies of the mechanisms by which mutations of nucleotide- 184 binding oligomerization domain 2 (NOD2) lead to Crohn’s disease we previously demonstrated that muramyl dipeptide EFFICACY OF THE DIAGNOSTIC PROTOCOLS OF (MDP) activation of NOD2 causes negative regulation of INFANTS WITH CHOLESTASIS RELATED TO peptidoglycan-mediated stimulation of Toll-like receptor ANATOMICAL AND NON-SURGICAL ETIOLOGY (TLR) 2 and that in the absence of such activation, TLR2 Maria del Carmen Bojorquez Ramos, Laura M. Bayardo- signaling leads to heightened Th1 Interleukin (IL)-12 mediated Ram´ırez, Alfredo Larrosa-Haro. Gastroenterologia y Nutricion, responses. The above data focusing on NOD2 function with UMAE Hospital de Pediatria CMNO IMSS and Unidad de respect to TLR2 signaling does overlook evidence that Investigacio´nMe´dica. Instituto de Nutricion Humana U de multiple TLR signaling pathways are probably involved in G, Guadalajara, Mexico. the development of Crohn’s disease. This possibility led us in the present study to determine if NOD2 signaling has affects Background: Differential diagnosis of infants with cholestasis is on multiple TLR stimulation pathways not just TLR2. We found a challenge for pediatric gastroenterologists. In the 80s, 90s the that, indeed, pre-stimulation of APCs (human dendritic cells) goal was to identify biliary atresia, currently, the issue is the with MDP reduced pro-inflammatory cytokine production differential diagnosis of the cases without anatomical abnorm- (IL-12p70, IL-6, TNF-alpha, IFN-gamma) upon subsequent alities. The aim of this work was to compare the diagnostic stimulation with TLR2, TLR3, TLR4, TLR5, and TLR9 efficacy of protocols used to perform differential diagnosis in ligands. These reduced responses were due to the induction both situations. of a protein that has recently been shown to be a negative Methods: Design: Case-report series. Study period: January regulator of TLR signaling, IRF4 (IFN regulatory factor 4). 2004 to June 2006. Protocol: All infants with cholestasis were Furthermore, we found that pre-treatment with MDP comple- included. Biliary atresia and choledocal cyst were searched by tely protects mice from trinitrobenzene sulphonic acid (TNBS) duodenal tube test and ultrasound. Non-surgical etiology was or dextran sodium sulfate (DSS)-colitis by down regulating investigated with serologic markers for viral hepatitis and these TLR-mediated mucosal cytokine responses. This STORCH; biochemical test for metabolic diseases included protection was not apparent when MDP was administered in galactosemia, tyrosinemia, cystic fibrosis, a-1 antitrypsin vivo in conjunction with a siRNA directed against IRF4. Thus, deficiency, hypothyroidism and hyperamonemic syndromes. these in vitro and in vivo studies demonstrate that MDP Liver biopsy was performed in 32 (42%) cases. A final review stimulation of NOD2 signaling has widespread suppressive

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E72 effect on a multitude of TLR responses (not only TLR2) and Background and Aims: We have found that anti-GM-CSF auto- point towards the possibility of this molecule as a therapeutic antibodies which neutralize GM-CSF bioactivity are up regulated modality in those Crohn’s patients who have an intact NOD2 in CD. The aims of the current study were to determine the signaling pathway. relationship between anti-GM-CSF and current IBD immune responses, and their association with disease phenotype. 186 Methods: 200 children with CD and Ulcerative Colitis (UC) with an average of four years follow-up were enrolled. Disease INCIDENCE OF BONE MARROW APLASIA AND location and behavior were classified using the Montreal LEUKOPENIA IN THIOPURINE THERAPY IN system. GM-CSF, ASCA, OmpC, I2, and CBir1 antibodies CHILDREN WITH INFLAMMATORY BOWEL were determined by ELISA. Genotyping for CARD15 DISEASE AT A SINGLE CENTER R702W, G908R, and 1007fs was performed. Keith Benkov, Kathy Hoffstadter-Thal, Jytoi Sinha, Clare Results: Circulating anti-GM-CSF was up regulated ten-fold in Ceballos, David Dunkin, Nanci Pittman. Division of Pediatric CD patients with small bowel involvement. After controlling for Gastroentrology, Mount Sinai Medical Center, New York, NY. CARD15 SNP carriage and disease location, forty percent of CD patients with serum anti-GM-CSF 2 mg/ml experienced Introduction: Thiopurine therapy (TT) with either 6-mercapto- stricturing or penetrating disease behavior and required surgery, purine (6MP) or azathiopurine (AZA), has become the mainstay compared to 17% with lower levels, P = 0.002. This was maintenance therapy for inflammatory bowel disease (IBD) in comparable to the increased risk for surgery associated with children. Various strategies have been debated regarding the need positive ASCA serology. 76% of patients positive for anti-GM- to determine thiopurine methyltransferase (TPMT) activity. CSF were also positive for ASCA, OR = 12, P < 0.001. Elevated Severe TPMT deficiency can lead to life-threatening bone anti-GM-CSF was not associated with OmpC, I2, or CBir1. The marrow aplasia (BMA). surgical rate increased from 14% in CD patients positive for 0 or Aims: 1) Determine the incidence of bone marrow aplasia in a 1 serological markers (n = 78), to 35% in those positive for 2 or large cohort of children receiving TT. 2) Determine incidence of 3 (n = 57, OR = 3.2), and 50% in those positive for 4 or 5 (n = 22, leukopenia in children with close follow-up. OR = 6). 73 CD patients were positive for anti-GM-CSF and/or Methods: A preexisting database of 1187 children with IBD ASCA, with a surgical rate of 41%, while the remaining 84 were seen at the Children’s IBD Center at Mount Sinai from 1/95 to negative for both, with a surgical rate of 11%, OR = 5.5, 5/07 was queried regarding all children who received TT >4 P < 0.001. weeks, as well as the incidence of BMA. The number of Conclusions: The combination of anti-GM-CSF and ASCA children who had TPMT levels were queried. The incidence can be used to identify CD patients at higher risk for surgery. of leukopenia was determined among a closely followed group GM-CSF administration may be beneficial in this subset of on TT over a 12-mo period. patients. Results: A total of 428 children received TT >4 wks, of which 312 had Crohn’s disease (CD), 104 had ulcerative colitis (UC), 188 and 12 had indeterminate colitis (IC). Only 31 children had TMPT levels, measured, of which 3 had intermediate activity. MUC1 IN PEDIATRIC INFLAMMATORY BOWEL There was not a single occurrence of BMA. 87 children on 6MP DISEASE 1 1 2 1 for >6 months on average dose of 1.4 mg/kg were observed A. Furr , S. Ranganathan , O. Finn . Gastroenterology, over a 12 months. There were 140 episodes of leukopenia Children’s Hospital of Pittsburgh, Pittsburgh, PA; 2 (wbc <4,000) in 1046 CBCs. The frequency of leukopenia Immunology, University of Pittsburgh. was 13.3% with 1.6 episodes of leukopenia/patient year. Discussion: At a large singe center, where TPMT activity is not Background and Aims: MUC1 glycoprotein is found on the routinely measured, there was no report of bone marrow aplasia apical surfaces of ductal epithelial cells. In normal colon, nor was there an increased incidence of leukopenia. While this MUC1 is heavily O-glycosylated and expressed at low levels. might a fortuitous occurrence, the risk of aplasia may not be as Hypoglycosylated form of MUC1 is overexpressed in colon frequent as stated. Leukopenia is a fairly common clinical cancer. This form of MUC1 is immunogenic and patients with occurrence and may not be an impairment to successful therapy. colon cancer have anti-MUC1 antibodies. Little is known about Further evaluation needs to be done before deeming TPMT expression of MUC1 in inflammatory bowel disease (IBD). We activity levels as standard care before initiating TT. studied children with IBD for the presence of hypoglycosylated MUC1 at sites of inflammation and for anti-MUC1 antibodies 187 in serum samples. We hypothesized that both the MUC1 and the antibody would correlate with the degree of inflammation and GM-CSF AUTO-ANTIBODIES AND DISEASE thus be potentially useful in monitoring disease progression and BEHAVIOR IN CROHN’S DISEASE (CD) response to therapy. Lee Denson1, Marla Dubinsky3, Mi-ok Kim5, Diane Black2, Methods: Colonic biopsy specimens were analyzed by immu- Kanji Uchida2, Bruce Trapnell2, Subra Kugathsan4. nohistochemistry for the presence of normally glycosylated and 1Gastroenterology, 2Pulmonary Biology, 5Epidemiology, hypoglycosylated MUC1. ELISA was performed to detect Cincinnati Children’s Hospital Medical Center, Cincinnati, aMUC1 antibody. OH; 3Pediatric IBD Center, Cedars-Sinai Medical Center, Results: MUC1 was found in 60% of normal colon samples, Los Angeles, CA; 4Pediatric Gastroenterology, Medical College 53.8% of UC, and 64% of CD. In normal tissue, MUC1 was of Wisconsin, Milwaukee. localized to the apical surface of epithelial cells, with little

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E73 cytoplasmic staining. In inflammed tissue, this expression pattern was altered. MUC1 lost its apical distribution, and CD after IPAA No CD cytoplasmic staining was markedly increased. Hypoglycosy- (n = 6) (n = 68) P value lated MUC1 was found in 0% of normal colons, 69.2% of UC, and 57.1% of CD. Staining for hypoglycosylated MUC1 was Age at IPAA (yrs) 10.2 3.4 10.6 3.4 NS % female 67% 57% NS consistently intense in regions of regenerative epithelium. Sera Yrs of colitis at IPAA 1.5 1.2 2.8 1.2 0.044 from pediatric patients with IBD and healthy controls were Yrs f/u after IPAA 6.3 4.1 7.2 4.0 NS analyzed by ELISA. aMUC1 antibodies were detectable in the majority of IBD patients; levels of aMUC1 antibody dropped mean SD. significantly as clinical indices improved. Conclusions: MUC1 is overexpressed in aberrant, hypoglycosylated form in pediatric IBD. This aberrant form is absent in 190 normal, healthy colonic tissue. Circulating antibodies to hypoglycosylated MUC1 are found in patients with IBD, and antibody SEVERE PEDIATRIC ULCERATIVE COLITIS: A levels correlate with clinical disease severity. MUC1 may play an COHORT STUDY OF INCIDENCE, OUTCOME AND important role in the pathogenesis of IBD and anti-MUC1 PREDICTORS OF RESPONSE antibodies may serve as biomarkers of disease. Dan Turner, Catharine C. Walsh, Eric I. Benchimol, Robin A. McLernon, Christy Chow, Thomas D. Walters, Anne M. 189 Griffiths. Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, ON, Canada. CROHN’S DISEASE AFTER ILEAL POUCH-ANAL ANASTOMOSIS FOR ULCERATIVE COLITIS IN Background: 30% of adults hospitalized with severe ulcerative CHILDREN colitis (UC) fail to respond to intravenous corticosteroids Stephen E. Dolgin1, James Markowitz2. 1Pediatric Surgery, 2 (IVCS), but data concerning pediatric patients have been Pediatric Gastroenterology, Schneider Children’s Hospital, extremely sparse. NS-LIJ Health System, New Hyde Park, NY. Aims: 1) To evaluate the short (by discharge), medium (1 year) and long term (mean 6 years) outcome of IVCS Background: A recent series of children undergoing ileal therapy in pediatric UC 2) To identify variables predictive of pouch-anal anastomosis (IPAA) for Ulcerative Colitis (UC) IVCS failure 3) To assess incidence of admissions of UC reported subsequent Crohn’s Disease (CD) in 15%. We studied children. our series to learn if CD occurred that often, to clarify the Methods: Children with UC admitted for IVCS therapy outcome when CD develops and to determine if this occurrence (1991–2000) were included. Explicit data were extracted in is predictable. duplicates during admission, 1-year post discharge and at most Methods: A retrospective chart review was performed for all recent follow-up. Predictors were analyzed using univariate children undergoing IPAA for UC. All were operated upon by followed by a multivariable analysis. 5 predictive indices were one pediatric surgeon (SED). Charts were reviewed for clinical compared at day 3 and 5 of IVCS: the Pediatric UC Activity Index outcome. In children developing CD, data regarding pre-op (PUCAI), and the indices of Lindgren, Travis, Ho and Seo. signs of CD, colon histopathology and course after IPAA were Results: 120 children (49% males; age 11.5 4.3 years) with also collected. UC (90% extensive) were admitted for IVCS. These represent Results: 6 of 74 (8%) children developed CD after IPAA 28% (95% CI 23–34%) of UC patients followed by our (Table). All 6 had normal UGI-SBFT pre-op. None had a IBD program during that period. Median disease duration history of perineal disease, small bowel obstruction, skip was 3 months (IQR 0–13); 49% of admissions were at onset lesions or rectal sparing. 4/4 patients were pANCA positive, of disease. Colectomy rate at discharge was 42% (within 14 ASCA negative pre-op. Histopathology of resected specimens 6 days of IVCS). Several predictors were associated with was consistent with UC in 5/6. CD developed a mean of IVCS failure but in multivariable modeling only CRP 1.6 yrs after IPAA. Symptoms included bleeding, obstruction, (OR = 3.5 (1.4–8.4)) and number of nocturnal stools nocturnal accidents, perineal fistulas and malnutrition. (OR = 3.2 (1.6–6.6)) remained significant at both days 3 and 5/6 had CD in the afferent limb as well as in the pouch. 5 of IVCS. The PUCAI strongly predicted IVCS failure The child who had a normal afferent limb had chronic pouch (P < 0.001, area under ROC curve 0.81 (0.73–0.9) and 0.84 inflammation and a perineal fistula from the pouch. Treatment (0.72–0.92) at days 3 and 5, respectively). At 1-year post included 5-ASA, 6-MP, infliximab and reoperations discharge, 35% of the children discharged without colectomy (strictureplasty, pouch revision and temporary ileostomy with were steroid dependent. Cumulative colectomy rate were 58% a seton for a fistula). At a mean of 4.6 yrs after CD all still had at 1-year and 61% at 6-year follow-up. functioning pouches. Conclusions: Children with UC have higher admission, Conclusions: CD can develop in children after IPAA for UC, IVCS failure and colectomy rates, as compared with but the risk is lower (8%) than previously described. We could adults. More effective medical therapies are badly needed. not identify any pre-op characteristics suggestive of CD. With Clinical variables and the PUCAI, determined at day 3 and 5 appropriate medical and surgical interventions, adequate pouch of IVCS may help to guide the introduction of 2nd line function can be maintained. therapies.

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191 reactivity, suggesting that baseline serologic responses can identify children at risk for progression to complicated CD. USE OF A WEB-BASED DATA REGISTRY TO SHOW Aim: To evaluate whether race affects the association between IMPROVED IBD PATIENT MANAGEMENT 1,2 2 3 baseline immune responses and development of FS/IP CD. Charles M. Samson , Darshna C. Bhatt , Beth A. McLean , Methods: Sera from 737 prospectively followed children with Sandra C. Kim3. 1Gastroenterology, CCHMC, Cincinnati, OH; 2 3 CD were tested for immune responses to microbial antigens: Pediatrics, Pediatric Gastroenterology, University of North CBir1 flagellin (anti-CBir1), outer membrane protein C Carolina, Chapel Hill. (anti-OmpC) and S. cerevisiae (ASCA IgG & IgA) using ELISA. CD phenotypes were determined blinded to immune Background: The UNC Pediatric IBD clinic has utilized responses. Associations between the number of abnormal chronic care methodology validated by the UNC Cystic Fibrosis immune responses (0–2vs3–4) and CD phenotype were Center, with the goal of improving overall delivery of care to evaluated as a function of race. our patients. Results: A greater percentage of African Americans (AA) Aims: a. Create a single center, IBD patient web-based data (40%) had 3–4 abnormal markers compared to Caucasians registry; b. Utilize the registry to monitor the efficacy of an (21%, P = 0.0022). Asians (14%) and Hispanics (22%) were algorithm to optimize treatment of IBD patients, focusing on similar to Caucasians. AA were more likely to have FS/IP CD decreasing steroid use. compared to Caucasians (44% vs 29%, P = 0.03). Caucasians Hypothesis: Instituting a clinical algorithm to effectively use with 3–4 abnormal serologic markers were more likely to maintenance therapy will decrease the percentage of patients on develop FS/IP CD than those with 0–2 markers (40% vs chronic corticosteroids. 26%, P = 0.0017). However, no similar association was seen Methods: Data on pts with Crohn’s (CD), ulcerative (UC), and in the AA subjects (3–4: 50% vs 0–2: 39%, P = 0.5799). indeterminate colitis (IC) treated at the NC Children’s Hospital Findings were unchanged when perianal disease was excluded were collected (9/2003 - present) and entered into a web-based from the IP category, and when analysis was done utilizing registry (DocSite). Data was analyzed in 2 groups: 9/2003–4/ serologic data expressed as quartile sums. 2006 and 5/2006-present (pre- and post-algorithm). Visit plan- Conclusions: Increased immune reactivity is associated with ners were updated at all clinic visits, allowing population data to development of FS/IP CD in Caucasian but not AA children be tracked over time. despite AA being more likely to have FS/IP and greater immune Results: 237 pts (mean age: 14.7 3.7 yrs) have been entered reactivity. Further analysis and subject accrual are underway. If into the registry (48% CD, 33% UC, and 19% IC). Since the confirmed in a larger cohort, our data suggest that race should algorithm was instituted, the % of pts on chronic steroid therapy be taken into account when using serologic responses as a has decreased (pre: 45% vs. post: 33%) while the % of pts on biomarker for CD progression. steroids with a documented taper has increased (45% vs. 51%). Concurrently, the % of pts that are on immunomodulators 193 has increased (38% vs. 42%). The % of pts on infliximab has increased (10% vs. 16%); the % of pts on 6-MP/AZA has AGE AT DIAGNOSIS OF INFLAMMATORY decreased (28% vs. 26%). The % of asymptomatic pts on steroids BOWEL DISEASE (IBD) AND DEVELOPMENT has decreased (22% vs. 13%), while the % of pts on immuno- OF EXTRAINTESTINAL MANIFESTATIONS (EIMS) modulators that are asymptomatic has increased (36% vs. 44%). Folashade Jose1, Neera Gupta1, Elizabeth Garnett1, Eric There has been no significant change in the % of acute visits. Vittinghoff1, Barbara S. Kirschner2, George D. Ferry4, Conclusion: By using a web-based data registry, we have Stanley A. Cohen3, Oren Abramson5, Benjamin D. Gold3, shown that an algorithm has been effective in decreasing the Harland S. Winter6, Robert N. Baldassano7, Melvin B. percentage of patients on chronic steroids without adversely Heyman1. 1Pediatrics, University of California, San Francisco; affecting disease activity or increasing acute visits. Future 2University of Chicago Comer Children’s Hospital, Chicago, studies using this registry will focus on outcomes related to IL; 3Emory University School of Medicine, Atlanta, GA; 4Texas growth velocity, bone density, and progression to surgery. Children’s Hospital, Baylor College of Medicine, Houston, TX; 5Kaiser Permanente of Northern California, Santa Clara, CA; 6 192 Massachusetts General Hospital for Children, Boston; 7Children’s Hospital of Philadelphia, Philadelphia, PA. IMMUNE RESPONSES PREDICT DEVELOPMENT OF COMPLICATED CROHN DISEASE: EFFECT OF RACE Background: Identification of EIMs may lead to early diag- 1 2 1,3 2 J. Markowitz , M. Dubinsky , S. Kugathasan , L. Mei ,C. nosis of IBD. We examined the relationship of young age at 1 1 1 Langton , J. Hyams , of the participating Research Groups ,For diagnosis of IBD and development of EIMs. 2,3 1 all members . Pediatric IBD Collaborative Research Group, Methods: Data in the PediIBD Consortium Registry for 1631 2 Hartford, CT; Western Regional Research Alliance for patients diagnosed with IBD before 18 years of age [993(61%) 3 Pediatric IBD Research, Los Angeles, CA; Wisconsin IBD CD, 467(29%) UC, 171(10%) Indeterminate Colitis (IC)] were Research Alliance, Milwaukee. analyzed using Kaplan-Meier and log rank tests. Results: Median age at diagnosis of IBD was 12 yrs. Median Background: Crohn disease (CD) is a heterogeneous disorder age at EIM or end of follow-up was 15.7 yrs; 35 patients had characterized by diverse clinical phenotypes (inflammatory, follow-up to age 25. Estimated cumulative incidence of 1 EIM fibrostenosing [FS], internal penetrating [IP]). We have reported by age 25 was 34% (95% CI 31–38%). EIMs occurred earlier in an association between FS/IP CD and increasing immune life among children diagnosed with IBD at younger ages

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(P < 0.0005). EIMs presented prior to diagnosis in 24%, but Conclusion: Adalimumab was well tolerated in our pediatric were more likely to follow diagnosis of IBD (P < 0.0005) pts with CD, with 67% responding favorably. No serious (Table). Time from diagnosis of IBD to subsequent develop- adverse events occurred. Further studies are needed to evaluate ment of EIMs (P = 0.6) and cumulative incidence by 25 years of efficacy and determine optimal dosing of adalimumab in this age (P = 0.13) were similar. EIM incidence did not differ by IBD population. type (P = 0.69) or race (P = 0.73), but weak evidence was found for higher incidence of among girls (P = 0.07). 195 Conclusions: About one-fourth of EIMs are noted prior to diagnosis of IBD. EIMs appear earlier in life in children who are SHORT-TERM RESPONSE TO ADALIMUMAB IN younger at IBD diagnosis. Incidence after diagnosis of IBD and CHILDHOOD INFLAMMATORY BOWEL DISEASE cumulative incidence by age 25 do not appear to vary by age at Joshua D. Noe, Marian Pfefferkorn. Pediatric Gastroenterology, IBD diagnosis, IBD type, or race. Hepatology, and Nutrition, Indiana University School of Medicine, Indianapolis. Diagnosis of EIMs Background: Adalimumab, a humanized monoclonal antibody Age at IBD Dx before Dx after to tumor-necrosis factor, has been shown to be effective in short dx (yr) Total N IBD (%) IBD (%) term treatment of adults with moderate to severe Crohn’s disease (CD). There is limited data of its use in children with 0–5 210 6 (13) 40 (87) 6–12 720 43 (24) 138 (76) inflammatory bowel disease (IBD). 13–17 701 44 (27) 115 (73) Purpose: To evaluate IBD response in children treated Total 1631 93 (24) 294 (76) with adalimumab. Methods: A retrospective chart review was performed. We recorded indications for and dosage of adalimumab, concomitant 194 treatments, disease location, duration of infliximab use prior to SAFETY AND EFFICACY OF ADALIMUMAB IN adalimumab, and either the Pediatric CD Activity Index or the PEDIATRIC CROHN’S DISEASE PATIENTS Lichtiger Colitis Activity Index at various time intervals. For IBD Matthew Wyneski1, Alex Green2, Robert Wyllie1, Marsha Kay1, patients, we defined response to infliximab or adalimumab Lori Mahajan1. 1Cleveland Clinic Foundation; 2Metro Health as either a decrease in the disease activity index or remission Medical Center, Cleveland, OH. 3–6 months after treatment. Results: Ten patients were identified, ages 11 to 18 years old, when adalimumab was started. Three were males, 7 with CD Introduction: Attenuated response or anaphylaxis may develop and 3 with ulcerative colitis (UC). All 10 patients had colonic to infliximab. Adalimumab has recently emerged in the adult disease and upper tract disease. Eight patients responded to Crohn’s Disease (CD) population as an alternate TNF-alpha infliximab, 5 with CD and 3 with UC; two patients with CD inhibitor. No studies of adalimumab use in pediatric pts with CD had incomplete data for evaluation. Mean time between first have been reported. Our study aim was to examine the safety infliximab dose and the adalimumab dose was 29.5 months; and efficacy of adalimumab in pediatric CD pts. median was 24 months. Eight of the ten patients responded to Methods: Records of 15 pediatric pts with CD who received adalimumab 40 mg or 80 mg biweekly, or 80 mg loading dose adalimumab(Humira,AbbottLaboratories,AbbottPark,IL)were followed by 40 mg biweekly. The mean pediatric CD activity reviewed per an IRB approved protocol. All pts had a prior indices for patients with CD before and after adalimumab were attenuated response or anaphylaxis to infliximab. Pts and/or 12 and 4.2, respectively (normal is <10). The mean Lichtiger caregivers were trained on SQ administration of adalimumab at Colitis Activity Indices for patients with UC before and after home. They were to call the physician’s office if they experienced adalimumab were 9 and 5.1, respectively (normal is < 10). any illness or adverse reaction between visits. Other medications Seven patients were on corticosteroids when adalimumab was remained the same. Clinical response to adalimumab was classi- initiated and 4 of them were able to come off corticosteroids by fied as complete response, partial response, or nonresponse. 1 to 10 months after initiation of adalimumab. The 2 patients Results: 15 pts with CD were prescribed adalimumab over a that failed adalimumab required surgery and remained 33 months period. 1 pt was lost to follow-up. 14 had adequate on corticosteroids. follow-up for review. Mean age at start of therapy was 16.6 Conclusion: Adalimumab appears to be a useful alternative in (10.3–21.8) yrs. F:M ratio was 4:3. The majority of pts received pediatric IBD patients who have previously responded, but an 80 mg loading dose and 40 mg q2 wks. Average duration of became intolerant of infliximab. therapy was 10.8 months. A total of 272 injections were given. Of the 14 pts, 7 (50%) had complete response, 2 (14%) had a 196 partial response, and 5 (36%) had no response to adalimumab. Complete response was achieved on average after 5 injections. IMMUNOMODULATOR DISCONTINUATION IN Of 5 pts with fistulizing disease, 3 maintained fistula closure; 1 PEDIATRIC IBD PATIENTS RECEIVING SCHEDULED had temporary closure and 1 pt required surgery. 26 adverse INFLIXIMAB (IFX): CLINICAL CORRELATION WITH events occurred during 272 doses (9.6%). The most common IFX LEVELS AND HACA FORMATION adverse events were abdominal pain and nausea. There were Narayanan Venkatasubramani, Rebecca Ehlert, Karen Sherry, no serious adverse events and no adverse events required Richard Noel, Michael Stephens, Vincent Biank, Subra adalimumab discontinuation. Therapy was discontinued in Kugathasan. Pediatric Gastroenterology, Medical College of 2 pts due to insurance denial. Wisconsin, Milwaukee.

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Immunomodulatory (IM) therapy is often used in IBD with IFX Conclusions: We did not identify any events in which VS to reduce anti-IFX antibody (HACA) formation. REACH trial change alone led to a modification in the treatment plan. Our mandated concurrent use of IM in pediatric Crohn’s disease. data suggests that, in our setting of a busy infusion center, However, reports of hepatosplenic T cell lymphoma treated nursing time spent monitoring may be decreased without loss of with IFX + IM made clinicians to change this approach. IM was safety. Our current infusion protocol has been changed. After discontinued in many of our patients based on physician dis- the initial infusion during which VS are monitored every cretion. We determined the continued IFX efficacy, trough IFX 30 min, for subsequent infusions VS are monitored at initiation levels and HACA formation in patients receiving maintenance and 30 min after end of the infusion, just prior to discharge. IFX monotherapy vs. combination therapy (IFX and IM). Patients continue to be closely monitored by infusion center Clinical relapse/loss of response was defined as need for IFX nursing staff for signs and symptoms of IV infiltration and dose escalation, reduced infusion intervals or additional IBD adverse reactions. therapies. Since early 2006, combination therapy was continued in 39(40%) patients and IM was discontinued (IFX monotherapy) in 58 (60%). At 1 yr follow up, no differences in efficacy Pre-study VS protocol Every 30 min for duration was observed before and after discontinuation in patients of each infusion receiving IFX monotherapy. Similarly, no difference in efficacy Current VS protocol Initial infusion: every 30 min Subsequent infusions: at initiation was seen between the IFX monotherapy and the combination and 30 min after end therapy groups. Trough IFX level was available in 70 (72%) patients during the time of IM discontinuation and again 10 months later in 22 (23%) patients. Detectable IFX and no HACA were found in 51/70 (72%) and negative in 14 (20%). 198 There was a decline in IFX level in 22 patients where USE OF RIFAXIMIN IN PEDIATRIC PATIENTS WITH repeat levels were available. However, when two groups INFLAMMATORY BOWEL DISEASE (IFX monotherapy and IFX+IM) were analyzed separately, Pramodha Muniyappa1, Reema Gulati2, Vera Hupertz1. the decline was significant in IFX monotherapy group but 1Pediatric Gastroenterology, The Cleveland Clinic, not in the group where IM was continued. HACA occurred 2Metro Health Medical Center, Cleveland, OH. in 3/12 IFX monotherapy group compared with 0/10 in IFX+IM group. In pediatric IBD with sustained remission on combination therapy, discontinuation of IM does not increase the risk Background: Rifaximin is an antimicrobial approved by the of relapse or decrease the clinical efficacy in short term. U.S. FDA in 2004. It has poor systemic absorption and in vitro However, decline in IFX levels with HACA formation is seen activity against enteric Gram-positive and Gram-negative in IFX monotherapy. Longer follow up is needed to determine if bacteria making it a reasonable option for GI infections. Adult IM discontinuation results in clinically significant loss of studies that have been done show promising results evaluating response and more HACA formation. the efficacy of Rifaximin for use in inflammatory bowel disease (IBD). Methods: A retrospective IRB approved study of 23 children 197 ages 8–21 yrs was conducted at the Cleveland Clinic in patients with known diagnosis of IBD. We collected data including the MONITORING FREQUENCY DURING INFLIXIMAB time of diagnosis, extent of disease involvement, previous INFUSION treatments, more recent treatments and current symptoms. 2 1 2 Ellen M. Servetar , Edward J. Hoffenberg , Debra Schissel . While on Rifaximin, symptom improvement and lag to 1 Pediatrics, University of Colorado-Denver Health Sciences improvement were evaluated. 2 Center and The Childrens Hospital, Denver, CO. Results: Review of the data revealed that of the 23 patients, 12 had Crohn’s and 11 had Ulcerative Colitis with a mean age of Background: Our protocol for infliximab infusions includes 15.08 yrs. The most common complaints were diarrhea (87%), monitoring of vital signs (VS) and adverse events (AE) at abdominal pain (74%) and bloody stools (65%). Of the 23 patients 30 min intervals. We sought to evaluate whether less frequent that were prescribed Rifaximin only 3 were prescribed concurrent VS monitoring might be as safe. steroids. Patients were given Rifaximin at varying doses from Methods: Beginning in November 2005, we conducted a 400 mg to 1200 mg per day. Analysis revealed that of the prospective descriptive study in a hospital day infusion center. 20 patients that presented with diarrhea 16 had relief of diarrhea All patients receiving infliximab were eligible. The infusion within 4 weeks of treatment, 5 within 1 week of starting Rifax- was conducted per manufacturer guidelines, with monitoring imin. In 17 patients that presented with abdominal pain, every 30 min. Variables monitored included: age, dose, current 12 patients had relief within 4 weeks, 3 of these patients had medications, premedications, VS, chills, itching, hives, chest relief within 1 week. Visible bleeding resolved in 10 of15 patients pain or pressure, shortness of breath, headache, nausea, and within 4 weeks of therapy, 3 of the 10 had improvement within 1 vomiting. week. Only one patient had a negative side effect of temporary Results: Over 20 months, 25 patients were enrolled, and increase in diarrhea symptoms upon starting the Rifaximin. data obtained on their 104 infusions. One anaphylactic reaction Conclusions: Rifaximin was well tolerated in our pediatric occurred within 10 min of infusion initiation, and the infusion patients with IBD and showed favorable results. No serious was discontinued and the patient was treated for the infusion adverse events occurred. Larger prospective studies with stan- reaction. Two patients reported chest pain without changes in dardized dosages are needed to evaluate efficacy and determine VS and infusion was completed without modification. optimal dosing of Rifaximin in this population.

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199 Methods: Eighteen children 7–18 yrs with moderately active CD on CTX were randomized to begin GH, 0.075 mg/kg/day, or NONTHERAPEUTIC 6-THIOGUANINE (6TG) LEVELS continue CTX alone. Patients on infliximab were excluded but IN IBD PATIENTS AT THE START OF INFLIXIMAB other immunotherapy (IT) was not. Disease activity and muco- THERAPY sal healing were determined at 12 wks. Controls began GH at 12 Shaista Safder1,2, Judy Splawski1,2. 1Pediatrics, Rainbow 2 wks and were re-assessed at 24 wks. GH responders (PCDAI Babies and Children’s Hospital, Case Western Reserve 10 or PCDAI decrease 15 after 12 weeks) continued it for an University, Cleveland, OH. additional 52 weeks. Results: Nine subjects were randomized in each arm; the Introduction: Studies have shown therapeutic 6TG levels groups did not differ for age, sex, Tanner stage, disease activity, (>230–260 pmol) are associated with higher clinical remission or current CTX or IT. The Pediatric CD Activity Index (PCDAI) rate in IBD patients. (Osterman, Lewis: Gastroenterology decreased in the GH group, 30 16 vs 9 8, P = 0.01 vs 2006;130:1047–1053). controls, and did not change in the control group, 33 11 vs Purpose: The study aim was to analyze 6TG levels in patients at 23 12. In controls who crossed over to GH, disease activity the start of infliximab therapy to see if they were therapeutic also decreased, 23 12 vs 4 3. QOL measured by the (>230 pmol). IMPACT questionnaire increased in both groups. There was Methods: We retrospectively reviewed IBD patients on inflix- a trend towards a reduction in the CD Endoscopic Index of imab with recorded data regarding 6TG level prior to first Severity (CDEIS) in the GH group, 8 8vs4 4, with no infusion, azathioprine (AZA) dose, duration of treatment with change in the controls. Height velocity (HV) did not change in AZA prior to initiating infliximab, thiopurine methyl transfer- the controls. HV (cm/yr) increased in the GH group, 5 3vs ase (TPMT) enzyme activity level and extent of disease. 8 3, P = 0.003 vs controls, and in the controls after crossing Results: We included 37 patients on infliximab, 18 Male, over to GH, 3 3vs7 3. Sixty percent of the GH 19 Female; mean age: 13.8 2.6 yrs; 33 Crohns, 3 Ulcerative responders who entered the 52 wk extension phase (n = 15) Colitis, 1 Indeterminate Colitis. 11 of 11 patients had normal have maintained remission, with a mean follow-up of TPMT activity. We found only 11 (29.7%) of our patient 40 wks. HV has remained at 8 3 cm/yr. GH was well tolerated population had therapeutic 6TG levels prior to initiating inflix- with no unexpected safety signals. imab therapy. The AZA dosing in our therapeutic 6TG level Conclusions: GH is safe and effective as an adjunct to CTX population (2.3 0.6 mg/kg) vs non therapeutic 6TG group for treatment of disease activity and growth failure in (1.99 0.4 mg/kg) was not different (P = 0.08). With the excep- moderately active pediatric CD. A larger multi-center trial tion of one patient whose duration of treatment with AZA was is warranted. 2 weeks prior to infliximab, the range of AZA therapy was 3–45 months. Mean duration of 13.9 8.5 months in the therapeutic 201 6TG group vs 12.9 12.2 months in the non-therapeutic 6TG group. ONE-YEAR OUTCOME FOLLOWING Conclusion: We found that 2/3 of our IBD patients did not DISCONTINUATION OF CONCOMITANT achieve therapeutic 6TG levels prior to initiating Infliximab IMMUNOMODULATOR THERAPY IN therapy. We also found that AZA dose did not affect the 6TG INFLIXIMAB-TREATED CHILDREN WITH levels. The causes for sub-therapeutic 6TG levels are multi- CROHN DISEASE factorial including non-compliance, side effects, poor absorp- M. Sherlock, E. I. Benchimol, D. Turner, T. Walters, M. Zachos, tion, and acutely ill patients in whom waiting for therapeutic A. M. Griffiths. The Hospital for Sick Children, University of levels would delay recovery. Toronto, Toronto, ON, Canada. Implication: We suggest that establishing therapeutic 6TG levels could result in more patients achieving and maintaining Background/Aims: Clinical trial data indicates that regularly remission and thus avoid the need for infliximab or other scheduled infliximab infusions are associated with a low rate of immunosuppressive agents with severe side effects. These infliximab antibody (ATI) formation, and that concomitant agents should be reserved for the most severe cases. immunomodulation does not significantly enhance efficacy. In light of these data and the recent observation of hepatosplenic 200 T-cell lymphoma (HSTCL) in young patients with Crohn Dis- ease receiving dual therapy, infliximab monotherapy has A RANDOMIZED TRIAL OF GROWTH HORMONE become common. We reviewed 1 year outcome following (GH) IN ACTIVE PEDIATRIC CROHN’S DISEASE (CD) immunomodulator (IM) discontinuation. 1 1 1 4 Lee Denson , Ramona Bezold , Susan Moyer , Edgar Ballard , Methods: In May 2006, all patients receiving infliximab were 1 1 3 Rebecca Carey , Bankole Osuntokun , Barbara Lippe , David systematically counselled concerning the occurrences of 2 1 2 4 Klein . Gastroenterology, Endocrinology, Pathology, HSTCL and were informed that the causative role for azathiopr- Cincinnati Children’s Hospital Medical Center, Cincinnati, ine (AZA) or infliximab alone or in combination was unclear. 3 OH; Genentech, San Francisco, CA. Following discussion, patients and families decided on subsequent therapy: monotherapy with infliximab, AZA alone, or Background: GH may relieve symptoms in adults with CD, and continued dual therapy. Data concerning disease activity improve growth in children. We hypothesized that the addition (PCDAI), ATI development, infusion reactions and loss of of GH to corticosteroid therapy (CTX) would improve disease response were recorded in 1 year follow-up and compared with activity and growth in pediatric CD. the preceding year.

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Results: 27 patients, 16 male (59%), mean age 14.7 improved growth at one year compared to corticosteroid depen- 2.27 years, with Crohn Disease, had received infliximab main- dence. Subjects younger than 9 years at diagnosis had better tenance therapy for 1.81 0.99 yrs in combination with AZA growth outcomes; those with isolated small bowel disease were (n = 20), or methotrexate (MTX, n = 7). 25 discontinued IM twice as likely to have abnormal growth. therapy; 1 remained on dual therapy with MTX; 1 discontinued Conclusions: Growth delay persists in many children with CD infliximab. 5/25 (20%) required infliximab dose increases for following diagnosis despite the frequent use of immunomodu- active symptoms. Four had detectable ATIs at follow-up, lators and biologics. Additional strategies to improve growth associated with diminution in response and severe infusion outcomes require development. reaction in one. The table shows disease activity and infliximab regimens 6 months prior to change to monotherapy and at follow-up. 203 Conclusion: Families wish to continue infliximab in spite of COMPLEMENTARY AND ALTERNATIVE MEDICINE rare but serious adverse events. Discontinuation of concomitant USE BY PEDIATRIC IBD PATIENTS AND FAMILIES IN IM in children does not compromise the short-term efficacy of THE WESTERN UNITED STATES infliximab. Allison Wong1, Dorsey Bass1, Marla Dubinsky2, Gary Silber3, Philip MacDonald4, Richard Quan5, Michele Favreau6,J.A. Quiros5. 1Pediatric Gastroenterology, Hepatology and 6 months before One year Nutrition, Lucile Packard Children’s Hospital, Palo Alto, CA; Time discussion At discussion follow-up 2Inflammatory Bowel Disease Center, Cedars-Sinai Medical 3 Mean PCDAI 9.5 11.27 3.5 3.75 6.7 7.52 Center, Los Angeles, CA; Pediatric Gastroenterolgoy, Phoenix Mean inﬂiximab 6.2 mg/7.7 weeks 6.6 mg/ 6.8 mg/7.4 weeks Children’s Hospital, Phoenix, AZ; 4Pediatric Gastroenterolgoy, dose (mg/kg) 7.8 weeks Sutter Medical Center, Sacramento, CA; 5Pediatric and dose interval Gastroenterology, University of California-Davis Medical Center, Sacramento; 6UC Davis School of Medicine, Davis, CA.

Background: Inflammatory bowel disease (IBD) is a chronic 202 disease that is often treated with long-term prescription drugs. The chronic nature of IBD, its relapsing and remitting course, and EFFECT OF CURRENT TREATMENT PARADIGMS ON the adverse effects associated with standard therapy motivate GROWTH IN PEDIATRIC CROHN DISEASE some patients and their families to seek alternative therapies. In M. Pfefferkorn, G. Burke, A. Griffiths, J. Markowitz, J. Rosh, 2002 Heuschkel et al reported 41% of pediatric IBD patients were D. Mack, A. Otley, S. Kugathasan, J. Evans, A. Bousvaros, using some form of complementary and alternative medicine S. Moyer, R. Wyllie, M. Oliva-Hemker, R. Carvalho, (CAM). Their study included patients from Detroit, Boston and W. Crandall, D. Keljo, T. Walters, N. LeLeiko, J. Hyams. London. The aim of our study is to describe the use of CAM by Pediatric Inflammatory Bowel Disease Collaborative pediatric IBD patients in the Western United States. Research Group, Hartford, CT. Patients and Methods: 121 families and patients (ages 4– 25 years) with inflammatory bowel disease from 5 Pediatric Background and Aims: Growth abnormalities are common in IBD centers in California and Arizona were surveyed regarding children with Crohn disease (CD). We analyzed growth out- their use and experiences with CAM. comes in children newly diagnosed with CD and determined if Results: 72% of participants reported using some form of CAM growth abnormalities persist despite current therapies. for IBD. The most commonly used therapies were probiotics Methods: Clinical and growth data were prospectively obtained (46%) and food supplements (37%). 50% of probiotics and 30% on an inception cohort <16 years of age at diagnosis and Tanner of food supplements were prescribed by the GI physician. 76% I-III during the study period. of study participants reported that their child’s GI physician was Results: 176 children (mean age 10.1 years 2.8 SD, 65% aware of their CAM use. The most commonly cited reasons for male) with mild (33%) or moderate/severe (67%) disease at using CAM were a desire to feel normal again, a desire to boost diagnosis were studied. Disease activity was inactive/mild 89%) the immune system, and recommendation by a physician. or moderate/severe (11%) at one year, and inactive/mild (90%) Conclusions: CAM use is common in children with IBD. The or moderate/severe (10%) at two years. First year treatments prevalence of CAM use and the degree of physician acceptance included immunomodulators (60%), corticosteroids (77%), in our study population was higher than in previously published 5-aminosalicylates (61%), infliximab (15%) and enteral nutri- studies of CAM use in pediatric IBD. This difference may be tion (10%). By two years 86% had received immunomodulators due to regional differences in the acceptance of CAM by both and 35% biologic therapy. Mean height Z scores at diagnosis, the public and physicians in the western United States. 1 year and 2 years were 0.49 1.2 SD, 0.50 1.2 SD and 0.46 1.1 SD, respectively. Ten percent, 8%, and 6.5% of 204 subjects had height Z score <2 SD at diagnosis, 1 year, and 2 years. Abnormal height velocity Z score <1 SD was seen in PRACTICES AND PERCEPTIONS OF ENTERAL 45% of subjects at 1 year and 38% at 2 years. The mean height NUTRITION AS PRIMARY THERAPY FOR CROHN’S velocity Z score, however, increased from 0.71 to 0.26 DISEASE: THE NORTH AMERICAN PERSPECTIVE (P < 0.03) between 1 and 2 years. Corticosteroid-sparing M. Stewart, A. Otley. Pediatrics, Division of Gastroenterology, therapy or fast response to corticosteroids was associated with Dalhousie University, Halifax, NS, Canada.

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Background: Despite evidence of efficacy for induction of was also carried out for early BUD users with disease limited remission and mucosal healing, the use of exclusive enteral to ileum and/or ascending colon (IAC), compared with non- nutrition (EEN) for Crohn’s Disease (CD) remains infrequent in users with similar disease distribution. North America (NA). This is in stark contrast to the frequent use Results: 38/640 (6%) CD children received early BUD reported in Europe. (mean age 12.6 2 yrs, 66% male, 37% mild and 63% moderate Aim: To explore determinant(s) and patterns of EEN use by NA CD activity). BUD was prescribed for at least 1 child in 11/20 pediatric gastroenterologists (PGs). centers participating in the Registry. Only 19 (50%) had CD Methods: A survey was developed by an iterative process and limited to IAC location, while the remaining 19 had disease pilot tested. Members of NASPGHAN were contacted by email located in additional sites in the proximal small bowel or distal and given a hyperlink for Web-based completion of the survey, colon. 10/38 (26%) initiated BUD as monotherapy, while the with two follow-up requests. remainder received concomitant drug(s), including 5-ASA in Results: 356/1129 (31.5%) eligible NASPGHAN members 22/38 (58%). BUD was stopped by six months in 34 (89%), from Canada and USA responded. 31 were excluded from including 14 (37%) who were switched to PRED within the first analysis as they had not treated 1 IBD patient within 3 months of therapy because of inadequate response to BUD. In 12 months. 200 (62%) respondents were male. 213 (66%) were the year following diagnosis, 22/38 (58%) received PRED, and in the range of 30 to 49 years of age. Country of practice was only 1 subject remained on BUD continuously. The 19 BUD USA in 86% and Canada in 14%. 59 (19%) of respondents were users with disease limited to IAC (cases) were compared to 88 trainees. 31% reported never using EEN, 54% sparse use, and non-users with similar CD distribution (controls). Mean age, 13% regular use. Canadian PGs reported significantly more use gender, Tanner stage, height/weight percentiles and disease than American PGs (P < 0.001). Currently working and activity were not significantly different between the two groups. previously working in a centre where EEN was used were Conclusions: Monotherapy with BUD at diagnosis was uncom- highly correlated with both the perceived appropriateness of mon and 1/3 of subjects started on BUD required step-up to EEN and the regularity of its use (P < 0.01). Only 6% of PRED within 6 months and 58% by one year. physicians using EEN reported often or always using maintenance EN to maintain remission. Canadian respondents were 206 more likely to report often or always using maintenance therapy than American respondents (OR = 3.08; CI 1.3–7.2). Compli- JUVENILE POLYPOSIS SYNDROME IN CHILDREN: ance issues were seen as both the main disadvantages of EEN by A RETROSPECTIVE MULTI-CENTER STUDY 1 2 1 the majority of physicians (70%) and as the major barrier to Yoram Elitsur , Jonathan E. Teitelbaum , Mary Rewalt , 3 1 increased use by non-regular users. Michael Nowicki . Pediatrics, Marshall University, 2 Conclusions: There are significant variations in the patterns of Huntington, WV; Pediatrics, Monmouth Medical Center, Long 3 use and the acceptance of enteral nutrition as primary therapy Branch, NJ; Pediatrics, University of MS Medical Center, for CD between Canada and the USA, with Canadian PGs Jackson, MS. showing greater use of EEN for their patients. Survey responses indicated that the use of EEN for CD is influenced by the extent Background: Juvenile polyposis syndrome (JPS) carries a risk to which physicians are exposed to its use both in their training for colon cancer. The natural history of this syndrome in and current practice setting. children is unknown. Aim: To review the clinical presentation and colonic findings of 205 children identified with JPS. Materials: A retrospective analysis of patients with JPS was BUDESONIDE USE AT DIAGNOSIS IN A LARGE collected from 3 medical centers in the US. JPS was defined as 3 MULTI-CENTRE PROSPECTIVE PEDIATRIC or more JPs in the colon. In each patient, a questionnaire with COHORT demographics data, family history of colon cancer, symptoms, A. Otley, J. Markowitz, T. Lerer, A. Griffiths, S. Moyer, and endoscopic findings at initial and f/u colonoscopy was N. Leleiko, J. Evans, D. Mack, J. Rosh, M. Pfefferkorn, completed. IRB approval was obtained. S. Kugathasan, D. Keljo, R. Baldassano, M. Kay, M. Results: A total of 34 children were recruited. The mean age Oliva-Hemker, A. Bousvaros, W. Crandall, R. Carvalho, and M:F ratio was 7.02 3.9 (median: 6y, range: 1.5–16y) and J. Hyams. Pediatric Inflammatory Bowel Disease Collaborative 1.4:1, respectively. GI bleeding was the clinical presentation in Research Group, Hartford, CT. all children, and genetic evaluation for mutations was not performed in any of the patients. Family medical history of Background: Given growth and osteoporosis concerns, colon cancer was reported in 9 (26%) children. A total of budesonide (BUD) has the potential of offering significant 230 JPs (mean: 6.8 JP/pt) were identified at initial diagnosis benefits over prednisone (PRED) for inducing remission in with a similar colonic distribution (C- 9%, Asc-18%, Tr- 16%, Crohn disease (CD). Dec- 19.5%, Sig- 23%, R- 14%). Pedunculated polyps were the Aim: To describe BUD use initiated within 30 days of diagnosis most common feature (85%) and the rest had sessile configur- in a large pediatric CD cohort. ation (15%). Histology revealed inflammatory polyps in all Methods: Data were derived from the Pediatric IBD Colla- polyps. In f/u endoscopies, adenomatous changes were noted in borative Research Group Registry, an observational inception 3 polyps. Follow-up colonoscopies, time period passed, and cohort begun in 2002. Children with CD were identified and endoscopy findings are presented in Table. ‘‘early’’ BUD users (started 30 days of diagnosis) were Conclusion: (1) The number of colon polyps in JPS decreases compared with the remaining cohort. A case-control study over time. (2) Polyps are distributed evenly throughout the

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E80 colon. (3) In most children, histology is benign, family hx of dren. In several reported series, JPs were solitary in 75% of colon cancer is negative, and genetic analysis is not performed. cases, typically pedunculated and small in size but may (4) Prospective studies on the clinical development, cancer rate, occasionally grow to large sizes or occur in large numbers, and colon surveillance in children are clearly warranted. as in juvenile polyposis syndrome. Around 90% of solitary JPs are found distal to the splenic flexure. Giant juvenile polyps (> 30 mm) are very rare in children. Rectal bleeding from JPs 1st colon. 1st f/u colon. 2nd f/u colon. 3rd f/u colon. usually results in low grade bleeding. There are anecdotal reports of massive rectal bleeding associated with multiple No pts. 34 20 8 1 No polyp 230 (6.8) 101 (5.3) 28 (3.5) 2 polyps in children, mostly with juvenile polyposis syndrome. (mean/pt) A 9 years-old previously healthy Hispanic boy with history of Time pass/pt 1.0 year 1.5 year 2 year recurrent abdominal pain and vomiting for 4 months presented (mean) with sudden onset of massive painless hematochezia and shock. Following 4 units of packed red blood cell transfusion and adequate hydration, the rectal bleeding spontaneously stopped. Meckel’s scan was unremarkable. Colonoscopy was performed and revealed a giant pedunculated solitary polyp in the traverse 207 colon. With the nature of the polyp and the degree of its local BACTEREMIA IN PEDIATRIC PATIENTS WITH invasion undetermined, elective surgical resection was opted SHORT BOWEL SYNDROME for. After resection, the polyp measured 3.2 2.2 1.7 cm. Its Jennifer M. Colombo1, Mary Anne Jackson2, Elizabeth M. stalk was 1.5 cm in length and 0.8 cm in diameter. Histological Lyman1, Michelle A. Manalang3, James F. Daniel1, William evaluation revealed features of a juvenile retention polyp. The O. San Pablo1, Ding-You Li1, Jennifer V. Schurman1, Craig A. child did very well after the surgery with no further bleeding or Friesen1. 1Gastroenterology, 2Infectious Disease, 3Hematology/ abdominal pain episodes. To the best of our knowledge, this is Oncology, Children’s Mercy Hospital, Kansas City, MO. the second reported case of a life threatening rectal bleeding in a child from a solitary juvenile polyp. In 1995, Murakami et al reported a case of massive lower GI bleeding in a woman Most pediatric patients with short bowel syndrome (SBS) requiring an emergent colectomy, who had a giant solitary require long term central venous access for intravenous nutri- juvenile polyp identified after examining the removed colon. tion to ensure adequate growth. Sepsis is a common, serious The exceedingly rare presentation with sudden massive rectal complication of indwelling central venous catheters. Patients bleeding in this child was preceded by unusually longstanding with SBS may be at higher risk for sepsis than other populations episodes of abdominal pain and vomiting. In a child due to comprised gut immunity and integrity. We evaluated with massive rectal bleeding, JP should still be considered, 25 pediatric patients with SBS requiring long term central as highlighted by this case. venous access (11,291 total catheter days) and compared them to 48 pediatric patients with standard risk acute lymphoblastic leukemia (ALL) requiring long term central venous access 209 (30,588 total catheter days) to determine the rates, risk factors and microbiology of central venous catheter infection. The DIAGNOSTIC YIELD OF CAPSULE ENDOSCOPY AND incidence of catheter infection was significantly higher in IMPACT ON CLINICAL MANAGEMENT IN A patients with SBS than in patients with ALL (11.04 7.5 vs. PEDIATRIC POPULATION 1.04 2.1/1000 catheter days, P <.001). The catheter infection Charles M. Samson, M. S. Moyer, Lee A. Denson, Ajay Kaul, rate was unrelated to the length of residual bowel or the Phillip Putnam, Gitit Tomer. Gastroenterology, Cincinnati presence of an ostomy. The most common organisms identified Children’s Hospital, Cincinnati, OH. in those with SBS included E. coli, E. faecalis, K. pneumoniae, S. aureus, S. hominis, and yeast. The rate of bacteremia in Background: Capsule endoscopy (CE) provides non-invasive patients with SBS is significantly higher than can be explained examination of the small intestine. Several studies have shown by the presence of a central venous catheter alone. Findings that CE has a significant diagnostic yield in adults. However, from this study support the inherent risk of developing central there is limited information on the diagnostic yield of CE and its venous catheter infection with intestinal flora in pediatric impact on pediatric patient management. patients with SBS. Future work will need to examine the Aims: To evaluate the indications for CE, its diagnostic yield mechanism of increased sepsis risk to improve clinical manage- and impact on management of pediatric patients. ment of this patient population. Methods: We retrospectively reviewed charts of all patients who underwent CE from 5/2004 to 5/2007 at CCHMC. We 208 examined the indications, previous work-up, CE findings, complications, and its effect on diagnosis and treatment. LIFE-THREATENING RECTAL BLEEDING DUE TO A Results: We reviewed 46 CE studies performed in 44 patients GIANT SOLITARY JUVENILE POLYP IN A CHILD (mean age 14 yrs; range 6–21). 62% of the capsules were Ahmed Dahshan. Pediatric GI & Nutrition, Oklahoma swallowed, and 38% were placed endoscopically. Indications University, Tulsa, OK. included evaluation for suspected Crohn’s disease (CD) (48%), GI bleeding (35%), patients with known IBD (13%), and Juvenile polyps (JPs) are a recognized cause for recurrent intussusception (4%). Adverse events reported were: 9% of painless rectal bleeding typically noted in preschool age chil- studies were incomplete; 7% of patients were unable to swallow

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E81 the capsule; and there was one incidence of equipment ing the compliance and preparation outcome of this flavor malfunction (2%). Of the 20 patients evaluated for isolated option should be performed. small bowel CD, only one was diagnosed with CD based on CE. In workup of GI bleeding, CE had a diagnostic yield of 46%, 211 including 1 Meckel’s, 1 CD, 2 small bowel ulcers, 1 vascular malformation and 1 small bowel varices. In 6 patients with PROSPECTIVE EVALUATION OF THE USE OF known IBD, CE had a diagnostic yield of 50%, including PEG3350 IN A TWO-DAY CLEAN OUT FOR 2 patients whose diagnosis was changed from ulcerative colitis COLONOSCOPY IN CHILDREN to CD. Overall, management was altered based on positive CE Rima Jibaly. Pediatric Gastroenterology, Hurley Medical findings in 19% of patients, including 40% of patients with Center, Flint, MI. known IBD, 23% of patients with GI bleeding and 12% of patients being evaluated for CD. Colonoscopy is an invaluable procedure to look for intestinal Conclusions: CE is a safe, non-invasive and useful tool for the disease–which makes an effective cleanout necessary for a evaluation of small bowel disease in children. Overall, CE had a successful colonoscopy. Colonoscopy itself is stressful for both higher diagnostic yield in patients with known IBD and GI parents and children–and finding a ‘‘kid-friendly’’ prep is very bleeding compared to patients with suspected small bowel CD. important to decrease that stress. Most preps are not well CE should be considered in selected pediatric patients with accepted by children or are too lengthy. One of the most suspected small intestinal disorders. accepted medications has been PEG 3350 without electrolytes, which has been used for constipation and bowel cleanout. However, a two-day prep has not been studied before. A 210 two-day prep of PEG 3350 without electrolytes with clear diet PROOF THAT SOME KIDS REALLY DO LIKE THEIR is used successfully in my practice. This study will evaluate its VEGETABLES: A NEW FLAVOR OPTION FOR PEG effectiveness and safety. All parents of patients who were 5 years SOLUTION of age or older were approached for participation in the study if Pramodha Muniyappa, C. Carter-Kent, L. Mahajan. Pediatric the child was undergoing a colonoscopy (procedure that requires Gastroenterology, Cleveland Clinic Foundation, Cleveland, a clean-out). After consent, all caretakers received the standard OH. handout about instructions and suggested food. Caretakers were given a diary to track doses used and any other procedures (eg, suppository, enema). On the day of the procedure, the parent Background: The aim of our study was to determine how and child completed the appropriate satisfaction questionnaire, mixing low sodium organic vegetable bouillon with Colyte and the parents completed the dehydration questionnaire. Post would compare to unflavored and fruit flavored options. procedure, the PI rated her satisfaction and the effectiveness of the Methods: A prospective IRB approved study of children ages clean out. Eleven patients were recruited. Their ages ranged from 8–18 yrs was conducted in the Division of Pediatrics at the 6 to 15 years. Three were female; eight were male. Majority of Cleveland Clinic. 100 children were enrolled and asked to taste parents and children reported they were ‘‘Very Satisfied’’ or 3 Colyte solutions: unflavored, cherry and vegetable bouillon. ‘‘Satisfied’’ with the medication. The PI felt the preps to be ‘‘Very 1 oz servings of each solution were placed in unlabeled covered Effective’’ or ‘‘Effective’’. None was found ‘‘Fair’’ or ‘‘Not cups. The order they received each of the 3 cups was random- Effective’’. Prospective data shows clean out to be safe, effective, ized. Each child rated the taste of each solution on a 4 pt scale and well tolerated. and identified the best and worst tasting flavor. Results: For each flavor, the frequency and percentage of each ranking (best, middle, and worst) were calculated. In addition, Dosing Information for PEG 3350 Without Electrolytes frequencies and percentages of the rankings were calculated based on the order the flavor was received and the flavor that Range for no. Mean no. of Mean patient was administered just prior to the flavor. The bouillon flavor of doses doses dose was chosen as favorite by 55% of children (95% CI: 44–66%), cherry in 30%, and plain in 15%. The plain flavor was chosen as Day 1 2–6 4.55 1.6 g/kg the worst flavor by 49%, while 27% and 24% found the cherry Day 2 5–8 5.55 1.8 g/kg and bouillon flavor to be worst, respectively. Both the bouillon (P < 0.001) and cherry (P = 0.004) flavors were significantly better ranked than the plain flavor. However, a statistically 212 significant difference between bouillon and cherry flavors was not observed. APPROPRIATE URINE COLLECTION TIMES FOR Conclusion: All prior studies of bowel preparation flavoring SITE-SPECIFIC GASTROINTESTINAL (GI) have compared fruit flavors to each other or to unflavored PERMEABILITY TESTING IN CHILDREN AND solutions. This study is the first to evaluate the addition of ADULTS bouillon flavor to the already salty and oily tasting PEG. Our Mark E. McOmber, Robert J. Shulman. Pediatrics, Baylor study not only showed this to be a viable option but that children College of Medicine, Houston, TX. actually preferred low sodium organic vegetable bouillon over standard fruit flavoring. Bouillon flavoring of PEG has not Background: Sucrose (S), lactulose (L), mannitol (M), and previously been considered or studied in trials of patients sucralose (SL) have been used to measure permeability at undergoing bowel preparation. A large prospective trial study- different sites along the GI tract. S/L, L/M, and SL/L ratios

J Pediatr Gastroenterol Nutr, Vol. 45, No. 4, October 2007 E82 reportedly measure gastric, small intestinal, and colonic 1/10 hypotension and 0/10 altered consciousness. 2/10 patients permeability, respectively (Gastroenterology 1998;114:83). had low-dose narcotic use prior to TMC. 7/10 underwent However, there are no data regarding the optimal urine collec- colectomy. B) Nested Case-Control: X-rays of 9 TMC patients tion times to maximize urinary sugar recovery. The goal of our were compared with 40 hospitalized UC controls. Differences study was to determine the time course of excretion of were noted in mean luminal diameters of the transverse colon these sugars. (66.1 16.4 mm vs 34.6 16.4 mm, P < 0.001) and small Methods: Five adults (20–53 yr) and 3 children (7–16 yr) bowel (27.3 4.7 mm vs 19.9 8.1 mm, P = 0.001). Area under drank 127.5 mL of a solution containing S (10 g/dL), L (5 g/dL), the ROC curve (AUROC) of the transverse colon diameter to M (1 g/dL), and SL (1 g/dL) 4 h after supper. Urine was col- predict TMC was 0.932 (95% CI 0.833–1.031) and the lected for 24 h starting at 30 min. Subjects fasted the first 12 h best cutoff was 58 mm (sensitivity 90%, specificity 95%). and avoided artificial sweeteners during the final 12 h. Peak AUROC for small bowel diameter was 0.806 (95% CI ratio was defined as maximum sugar ratio detected during the 0.663–0.948) and the best cutoff was 24 mm (sensitivity study. We also calculated the percent of the total dose recovered 80%, specificity 70%). at each time point. Data are given as median (range). Conclusions: TMC can occur at initial IBD presentation in Results: Peak S/L ratio was detected at 30 min (in adults and children but hypotension and altered level of consciousness are children) and declined thereafter. Peak L/M ratio in adults rare. TMC represents a high risk of colectomy and was occurred at 9 h (7–13.5 h) and in children at 11 h (range 10– not related to narcotic use in our cohort. Maximum transverse 14 h). Peak SL/L ratio in adults occurred at 16 h (15.5–26 h) and colon diameter 58 mm strongly suggests TMC in children in children at 11 h (11–19 h). Percent of the total dose of with IBD. L recovered was >95% in adults at 12 h (8–13.5 h) and in children was >95% at 11 h (10–14 h). In contrast, at these time 214 points percent of the total dose of SL recovered in adults was only 86.3% (76.2–92.3) and in children only 87.6% (72.5– RETROSPECTIVE REVIEW OF THE USE OF 98.3). FREQUENT DOSING OF PEG 3350 FOR TWO DAYS Conclusions: These preliminary data suggest that: 1) Gastric WITH CLEAR DIET TO ACHIEVE DISIMPACTION permeability (S/L ratio) can be measured at 30 min; 2) Small Rima Jibaly. Pediatric Gastroenterology, Hurley Medical intestinal permeability (L/M ratio) may best be measured Center, Flint, MI. between 7–14 h; 3) Colonic permeability (SL/L ratio) in adults may best be measured after 15.5 h and in children after 11 h; 4) Constipation is a very common childhood problem that has been The time of peak excretion and percent dose of the total dose estimated to account for 3% of general pediatrics visits and 25% recovered at each time point support the contention that L/M of pediatric gastroenterology visits. Disimpaction may be and SL/L ratios measure small intestinal and colonic per- stressful because of the taste of the medicine when given orally, meability, respectively. the route of administration (if rectal or nasogastric). Although PEG 3350 without electrolytes has been shown to be well 213 accepted and effective in treatment of constipation and encopresis in children, the effectiveness using aggressive cleanout for TOXIC MEGACOLON IN CHILDREN: CLINICAL AND the immediate relief to result in clear output similar to what is RADIOLOGIC CHARACTERISTICS expected for a colonoscopy cleanout has not been studied. The 1 1 2 Eric I. Benchimol , Dan Turner , Erika Mann , Robin A. study hypothesis is that using frequent dosing (3–5 per day) of 1 1 1 McLernon , Anne M. Griffiths . Gastroenterology, Hepatol- PEG3350 for 2 days with clear diet colonoscopy cleanout will 2 ogy & Nutrition, Diagnostic Imaging, The Hospital for Sick achieve disimpaction and resolve encopresis with no serious Children, Toronto, ON, Canada. adverse events. This was a retrospective review from 2005– 2006 of 64 charts with the diagnosis of constipation, fecal Background: Toxic megacolon (TMC) represents a severe impaction, or encopresis. Inclusion criteria were suspected fecal manifestation of inflammatory bowel disease (IBD), but impaction with or without fecal incontinence, cleaned out with pediatric criteria for recognition are lacking. frequent dosing of PEG3350 of up to five doses a day and clear Methods: Children with TMC were identified by 1) electronic diet for two days, and had follow up appointment in one or two search of hospital records using ICD codes (1988–2007) and months from first visit. Patients were excluded if they had radiology reports (1998–2007), and 2) chart review of all organic constipation. Twelve patients met criteria; 42 were ulcerative colitis (UC) admissions. TMC was confirmed using excluded due to the use of other meds, no F/U, etc. Symptoms adult diagnostic criteria (Jalen et al, 1969): ANY colonic on presentation and their relief by the follow up visit (one to two dilatation PLUS 3 of fever, tachycardia, leukocytosis or anemia, month) were evaluated. Any reported side effects were col- PLUS 1 of dehydration, altered consciousness, abnormal lected. 100% of encopresis resolved. 67% of the patients had electrolytes, or hypotension. Abdominal x-rays of TMC patients complete relief of symptoms; 33% had partial relief. No adverse were interpreted blindly by a radiologist and compared to those events were reported by telephone or at follow-up visit. of hospitalized UC controls. PEG3350 appears effective and safe for disimpaction and Results: A) TMC Cohort: Ten patients (median age 12.6 yrs, resolving encopresis when used aggressively as a 2-day 8 UC, 2 Crohn disease) with TMC were identified. 5/10 clean-out with clear diet. It is important for parents to continue developed TMC during first presentation with IBD. daily use after disimpaction to improve success. Education by 9/10 patients had fever, 7/10 tachycardia, 8/10 leukocytosis, physician and nurse is key to compliance and resolution of 9/10 anemia, 4/10 dehydration, 10/10 abnormal electrolytes, problem.

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215 Results: Heme induced HO-1 more effectively from the basolateral side in Caco-2 cells and mice intestine. After treatment A NOVEL BILIVERDIN AND BILIRUBIN SECRETORY with basolateral heme, Caco-2 cells secreted heme, BV and BR PATHWAY IN INTESTINAL EPITHELIAL CELLS in a time and dose-dependent manner. Prior induction of HO-1 Aliye Uc, John Stokes. University of Iowa, Iowa City. with heme increased the rate of secretion of BVand BR, but not Background: Heme is vital for all organisms: it participates in of heme. Absorption of heme was very small and appearance of the structure of hemoglobin and a wide range of enzymes. BV and BR in the basolateral solution was minimal. Hemoglobin break-down and enzyme turn-over can release free Conclusion: Intestinal epithelial cells actively participate in heme, which in turn can cause toxicity by generating reactive heme degradation by secreting heme, and metabolizing and oxygen species. Heme oxygenases provide cytoprotection by secreting some of the heme as BV and BR. Biliverdin degrading free heme and generating products with potent anti- and bilirubin secretory pathway may have a role in bilirubin oxidant and anti-inflammatory functions, such as biliverdin metabolism, intestinal inflammation and oxidative stress. (BV) and bilirubin (BR). Little is known whether BV and BR are generated and transported in the intestine. Our previous 216 work has shown a heme secretory pathway in the intestinal epithelial cells that could play an important role in maintaining ISOLATED POSITIVE IMMUNOGLOBULIN A body iron homeostasis and/or disposing of potentially toxic ANTIGLIADIN ANTIBODY IN CHILDREN amounts of heme. WITH GASTROINTESTINAL SYMPTOMS Hypothesis: Intestinal epithelial cells can metabolize heme via Nasira Roidad1, Kathryn Skitarelic2, Stacey Gillespie1, Wikrom heme oxygenase-1 (HO-1) and secrete its degradation products, W. Karnsakul1. 1Pediatrics, Robert C. Byrd Health Sciences BV and BR. Center, 2Pathology, WVU School of Medicine, West Virginia Methods: An intestinal epithelial cell model, Caco-2 cells were University School of Medicine, Morgantown. treated with heme from either apical (lumen) side for measurement of absorption or basolateral (serosal) side for measurement Background: The use of immunoglobulin G and A anti-gliadin of secretion. HO-1 induction was detected with immunoblot and antibodies (IgG, IgA AGA) for celiac disease (CD) screening real time RT-PCR. Mice were given oral (lumen) or intraperito- has been decreased due to higher specificity and sensitivity of neal (serosal) heme (50 mmol/kg) and HO-1 induction tissue transglutaminase and endomysial antibodies (tTG and was measured with immunoblot and immunohistochemistry. EMA). Greater values of IgA AGA (> 70 mg/ml) showed more Sham-treated animals were used as control. Heme and BV severe mucosal damage in proven and probable CD patients. transport was measured with spectrophotometry; BR was Aim: To determine whether IgA AGA has any clinical import- detected with chloroform extraction. ance in diagnosing CD in children.

Abstract 216 Table. Summary of Clinical Data of Children With Isolated Positive IgA AGA Vomiting, diarrhea, IgG, IgA AGA Family Age (y), abdominal (normal HLA Esophageal, Small intestinal Gluten-free history Case Gender pain <20 units) DQ2/8 gastric histology histology diet of CD Final diagnosis

1 12, M +,+,+ 97, 119 S,S Normal Villus atrophy, + S Bacterial overgrowth, occasional IEL possible CD 2 3, M +,+,+ 73, 70 +,S Mild reﬂux Focal villus atrophy, + S CD occasional IEL 33,M+,S,S 91, 30 n/a Lymphocytic Increased lymphocytes SSFood allergy esophagitis and plasma cells in duodenum, increased lymphoid aggregate 43,M+,S,+ 82, 99 S,+ Normal Lymphoid aggregate in SSFood allergy duodenum and rectum 5 15.5, M S,+,+ 54, 47 n/a Chronic non- Normal S + IBS atrophic gastritis 67,FS,+,+ 34, 36 n/a Chronic active Normal SSHelicobacter gastritiswith pylori gastritis Helicobacter pylori 7 10.5, F S,S,+ 45.7, 24.7 S,S Eosinophils in Eosinophils SSGastritis antrum, gastritis, in duodenum gastric erosion 8 3.5, F +,+,+ 3, 50 n/a n/a n/a SSPossible functional abdominal pain 9 13, F +,+,+ 2, 22 +,S n/a n/a SSCystic ﬁbrosis and malabsorption

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Methods: From May 2004 to May 2007, children with chronic tration may be beneficial in the subset of CD patients with history of GER, abdominal pain, diarrhea, or constipation at increased circulating ant-GM-CSF auto-antibodies. WVU Hospitals were evaluated for CD. IgA tTG and AGA in serum were determined by ELISA test and IgA EMA by 218 indirect immunofluorescence. Children with isolated positive IgA AGA were further evaluated by performing CD genetic REGULATION OF HYPOXIA INDUCIBLE FACTOR study (HLA DQ 2 & 8), gastrointestinal biopsies or diet IN INTESTINAL EPITHELIAL CELLS IN therapy. INFLAMMATION 1 2 1 Results: Nine children had isolated positive IgA AGA (negative Karina Irizarry , Sean P. Colgan . Pediatric Gastroenterology, 2 IgA tTg and EMA). 5 were male, 4 female (mean age, 7.8 y). Hepatology and Nutrition, Mucosal Inflammation Program, None had IgA deficiency. Seven underwent GI biopsies. Department of Medicine, University of Colorado, Denver, CO. Clinical data are summarized in the table. Conclusions: The sole appearance of IgA AGA in most child- Background: Hypoxia and inflammation occur coincidentally ren with GI symptoms may be interpreted as a non-specific in mucosal diseases such as inflammatory bowel disease (IBD). immunomodulation phenomenon. Higher levels of IgA AGA A number of studies have implicated hypoxia inducible factor may give more clinical significance in children with high index (HIF) as a regulatory pathway under such conditions. HIF is a of suspicion for CD. New generations of IgA tTG may increase transcription factor critical to adaptation to low oxygen states, the sensitivity in diagnosing CD. and genetic models have indicated that intestinal epithelial HIF provides protection in murine models of colitis. It is not known how IBD-relevant mediators might influence intestinal 217 epithelial HIF expression and function. Hypothesis: Inflammatory mediators involved in pathogenesis GM-CSF REGULATES MUCOSAL BARRIER of IBD modulate HIF expression and/or function. FUNCTION AND SUSCEPTIBILITY TO ILEITIS 1 1 2 Methods: Intestinal epithelial cells (Caco2 or T84 cells) were Xiaonan Han , Ingrid Jurickova , Kanji Uchida , Erin transfected with a luciferase reporter construct containing Bonkowski1, Bruce Trapnell2, Lee Denson1. 1Gastroenterology, 2 sequence corresponding to the erythropoietin hypoxia-response Pulmonary Biology, Cincinnati Children’s Hospital Medical element (HRE). Transfected cells were exposed to various Center, Cincinnati, OH. concentrations of TNF-a, IFN-g, IL-4 or PGE2 in the presence and absence of hypoxia (pO2 20 torr) for 24–48 h. HIF activity Background: We have found that anti-GM-CSF auto-anti- and expression were quantified by luciferase assay. bodies which neutralize GM-CSF bioactivity are up regulated Results: Hypoxia induced HRE activity in intestinal epithelia in Crohn’s Disease (CD) with ileal involvement. The efficacy of by as much as 18 3-fold (P < 0.001). An initial screen GM-CSF administration has been tested in recent clinic trials. revealed no significant influence of TNF-a, IL-4 or PGE2 on We hypothesized that loss of GM-CSF bioactivity would impair HRE activity. IFN-g, however, induced a concentration-depen- barrier function and increase susceptibility to ileitis. dent repression of HIF activity under both normoxic (P < 0.01) Methods: Intestinal permeability was measured in GM-CSF and hypoxic conditions (P < 0.01). The level of inhibition by deficient mice and wild type (WT) controls using the everted IFN-g (10 ng/ml) was as much as 65 5% and 93 8% in gut sac method, and bacterial translocation to mesenteric lymph normoxia and hypoxia, respectively, implicating a prominent nodes was quantified. Circulating T cell populations were and highly relevant repression by IFN-g. assessed by flow cytometry. A neutralizing anti-GM-CSF or Conclusions: HIF activity is prominently repressed IFN-g. This isotype control antibody (50 mg IP) was administered to WT observation may be relevant to the pathophysiology of colitis. mice. Two weeks later, WT mice pre-treated with anti-GM-CSF Namely, intestinal epithelial HIF has been implicated as a or IgG and untreated WT and GM-CSF deficient mice were protective element in animal models of colitis, and the loss placed on chow containing piroxicam, a NSAID, at 200 ppm. of HIF expression or function during inflammation may exacer- The effect upon weight gain, diarrhea, ileal and colonic inflam- bate inflammation. Ongoing experiments focus on defining mation, and circulating T cell populations was determined after molecular mechanisms of HIF regulation by IFN-g. two weeks. Results: Ileal, but not colonic, permeability was increased in 219 GM-CSF deficient mice at baseline. Bacterial translocation to mesenteric lymph nodes was also increased. The frequency of DUODENAL LYMPHONODULAR HYPERPLASIA AND circulating CD44+CD62L activated/memory T cells was FOOD ALLERGY IN INFANTS WITH PERSISTENT increased in GM-CSF deficient mice, while the frequency of DIARRHEA, EMETIC SYNDROME, AND GI CD4+CD25+FOXP3+ regulatory T cells was reduced. WT mice BLEEDING with or without IgG pre-treatment gained weight normally and Alfredo Larrosa-Haro2,4, Johnatan M. Mesa-Magan˜a2,1, Maria did not exhibit diarrhea or intestinal inflammation after pirox- R. Flores-Marquez3, Maria C. Bojorquez-Ramos1, Rocio icam administration. WT mice pre-treated with anti-GM-CSF Macias-Rosales1,2, Osvaldo Garcia-Salazar1, Yolanda A. antibody, and GM-CSF deficient mice, lost weight and devel- Castillo de Leon1. 1Gastroenterology and Nutrition, 2Medical oped diarrhea, splenomegaly, and ileal inflammation after Research Unit, UMAE Hospital de Pediatria, Guadalajara, piroxicam administration. Mexico; 3Pathology, UMAE Hospital de Especialidades, Conclusions: GM-CSF is required for intestinal barrier func- Guadalajara, Mexico; 4Human Nutrition Institute, University of tion and maintenance of ileal homeostasis. GM-CSF adminis- Guadalajara, Guadalajara, Mexico.

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Background: Food allergy/hypersensitivity (FAH) has the transfer of lipids onto apoB (a glycosylation pathway in increased from 2.8 to 8% (1993–2006) in the US. In Mexico enterocytes), is therefore a less likely diagnosis. a few studies show a similar trend. Studies by Kokkonen (1999) Conclusions: Several mechanisms other than PLE explain the and Iacono (2007) have found an association of lymphondular child’s diarrhea. A mutation of MTP is being sought to exclude hyperplasia (LH) and FAH in children. The aim of our study was ABL. The next question is whether decreased apoB levels could to evaluate such association in infants with persistent diarrhea, arise from abnormal glycosylation in enterocytes, a primarily emetic syndrome and GI bleeding. defect of CDG itself. Methods: Design: Cross-sectional. Study period: 2002–2006. Protocol: All cases with persistent diarrhea, emetic syndrome and Pancreatic Enzyme Assays From Duodenal Fluid Sampling by GI bleeding in whom upper endoscopy and mucosal biopsies Pre- and Poststimulation With Cholecystokinin were performed were included. Dependent variable: LH. Inde- pendent variable: FAH. Clinical, laboratory, endoscopic and Prestimulation Poststimulation Normal values Assays (mmol/ml/min) (mmol/ml/min) (mmol/ml/min) histological data were obtained from clinical files. FAH was diagnosed with the criteria exclusion/challenge to the suspicious Lipase 98.7 58.7 >146 2 formula or specific baby foods. Statistics: x , Fisher test, OR, CI. Trypsin 27.1 23.1 >55.4 Results: n = 123, mean age 8.7 5.6 months, 54.5% girls. Amylase 25.6 20.1 >32 Overall, 29.9% had persisten diarrhea, 34.5% emetic syndrome Protein concentration 4.5 (normal > 4.1 mg/ml). and 35.6% GI bleeding. 36 cases (29.3%) had FAH (cow’s milk 100%, soy-protein 33.3% and highly hydrolyzed protein 16.7%; in one breast fed case symptoms remitted when the mother was 221 placed on a cow’s milk-free diet). 30/36 children with FAH had duodenal LH and 6 out of 85 cases had LH but not FAH. The INTESTINAL PERMEABILITY IN AUTISTIC odds ratio was 49.4, CI = 15.1 to 90.6, P < 0.001. DISORDER 1,2 2 2 2 Conclusions: The frequency of FAH was higher than expected V. Familiari , L. deMagistris , A. Sapone , R. Esposito , 2 2 2 2 in the population under study. A significant association of FAH R. Riegler , M. Carten`ı , M. Generoso , P. Iardino , 2 2 2 2 and duodenal LH was found. The finding of LH by endoscopy T. Guardascione , C. Bravaccio , A. Frolli , A. Pascotto , 2 1 and/or by duodenal biopsy increases the probability of having R. Militerni . Mucosal Biology Research Center, University of 2 FAH. Endoscopy may become a useful diagnostic tool in third- Maryland, Baltimore; 1st School of Medicine, University of level patients with symptoms severe enough to require upper Naples, Naples, Italy. endoscopy for differential diagnosis. Background: It has been hypothesized that the abnormal intestinal permeability reported in autistic children may lead to 220 increased access of digestive products into the bloodstream, with MECHANISMS OF CHRONIC DIARRHEA IN A subsequent interference with central nervous system behavioural CHILD WITH CONGENITAL DISORDER OF functions, either directly or through an immune response to non- GLYCOSYLATION, TYPE 1A self antigens. Nasira Roidad1, Stacey Gillespie1, Kathryn Skitarelic2, Aim: To evaluate barrier function and intestinal inflammation Marybeth Hummel1, Wikrom W. Karnsakul1. 1Pediatrics, in children with autistic disorder and their first degree relatives. Robert C. Byrd Health Sciences Center, 2Pathology, Materials and Methods: Fifty-three autistic children (mean West Virginia University School of Medicine, Morgantown. age SD = 5.8 3.7; F = 3, M = 22) diagnosed according to the DSM-IV criteria, and 98 first degree relatives (mean Background: Children with congenital disorder of glycosyla- age SD = 38.5 8.3; F = 28, M = 22) were recruited. The tion (CDG) often present with severe diarrhea related to protein intestinal permeability was evaluated by means of lactulose losing enteropathy (PLE). and mannitol test (LA/MA). Faecal calprotectin was performed Methods: We cared for a 21/2 year old boy with CDG type 1a to evaluate an eventual intestinal inflammation. In all patients who had chronic diarrhea required some parenteral nutrition. serum anti-tissue transglutaminase antiboand HLA DQ2 DQ8 Introduced by solid food, he developed vomiting and were determined to rule out celiac disease. more diarrhea. An EGD with small bowel biopsies, assays of Results: In 41.7 % of patients with autistic disorder the LA/MA disaccharidase and pancreatic enzyme were performed. ratio was higher than the cut off value (0.030), while it was Results: Histology demonstrated partial villous atrophy with within normal limit in all 11 developmentally normal children increased intraepithelial lymphocytes indicating celiac disease tested as controls. In the group of first degree relatives, LA/MA with positive IgA tTG and fat vacuoles contained in duodenal resulted elevated in 27.8% of the subjects screened. Calpro- enterocytes suggesting abetalipoproteinemia (ABL). Low pan- tectin values, indicative of intestinal inflammation, resulted creatic enzyme (Table) and normal disaccharidase assays were elevated in 23/58 patients (39.6%), while only 6/109 (5.5%) noted.Gluten-free diet partiallyimproveddiarrhea andemesisbut of the relatives tested positive. a change to elemental formula with pancreatic enzyme supple- Conclusion: A large percentage of children affected by ment dramatically decrease diarrhea. Total cholesterol level was large spectrum of autistic disorder is characterized by altered 99 and triglyceride 65 mg/dL with normal fat soluble vitamin intestinal permeability and intestinal mucosal inflammation. levels. His apolipoprotein B (apoB) level dropped from 30 to < 27 The fact that a subgroup of their relatives also presented (55–140) and his parents’ apoB level 80 and 127 mg/dL. ABL, a elevated intestinal permeability without gut inflammation disorder caused by defects in the gene encoding microsomal suggest a genetic predisposition to impaired intestinal barrier triglyceride transfer protein (MTP), a chaperone that facilitates function leading to gut inflammation only in affected children.

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ORAL ABSTRACT PRESENTATIONS Pediatrics, 3Department of Medicine, 4Human Genetics, 2 SATURDAY, OCTOBER 27, 2007 University of California-San Diego; Department of Human Genetics, University of California-Los Angeles; 5Pathology, 10:15 AM – 11:45 AM Rady Children’s, San Diego, CA.

CELLULAR/MOLECULAR/ANIMAL MODELS Congenital Tufting Enteropathy (CTE) is a rare autosomal OF GI DISEASE recessive diarrheal disorder presenting in the neonatal period. CTE is characterized by intestinal epithelial cell dysplasia 222 leading to severe malabsorption and significant morbidity and mortality including dependence on parenteral nutrition. GLIADIN BINDING TO CXCR3 INDUCES A The pathogenesis and genetics of this disorder are not well MYD88- AND G-COUPLED PROTEIN RECEPTOR- understood. The objective of this study was to identify the gene DEPENDENT INCREASED INTESTINAL responsible for CTE. A family of Mexican-American descent PERMEABILITY AND ZONULIN RELEASE with 2 children affected with CTE was identified. The affected 1 1 1 1,2 2 K. Lammers ,R.Lu, J. Brownley , A. Sapone ,B.Lu,C. children are double second cousins providing significant 2 1 1 1 Gerard , S.N. Vogel , A. Fasano . MBRC, University of statistical power for linkage. Using Affymetrix 50K Single 2 Maryland School of Medicine, Baltimore; Children’s Hospital, Nucleotide Polymorphism (SNP) chips, genotyping was per- Department of Medicine, Harvard Medical School, Boston, MA. formed on only two patients and one unaffected sibling. Direct DNA sequencing of candidate genes was undertaken and Background: Increase in both zonulin release and intestinal RT-PCR and immunohistochemistry were performed on intes- permeability (IP) occur after apical but not basolateral intestinal tinal tissue from patients and controls. SNP homozygosity epithelial gliadin exposure, suggesting that gliadin interacts mapping identified a unique 6.5 MB haplotype of homozygous with a luminal gut receptor. Recently, we identified the che- SNPs on chromosome 2p21 where approximately 40 genes are mokine receptor, CXCR3, as the receptor for gliadin. located. LOD score was determined to be 4.7. Direct sequencing Aim: To explore the function of CXCR3 after gliadin binding. of genes in this region revealed homozygous G > A substitution Methods: CXCR3 expression in intestinal epithelial cells and at the donor splice site of exon 4 in Epithelial Cell Adhesion intestinal mucosa, gliadin binding to CXCR3, and signaling Molecule (EpCAM) of affected patients. Parents and an pathways activated by this binding were studied in vitro, using unaffected sibling were found to be heterozygous for this variant immunofluorescence microscopy, real time (rt) RT-PCR and consistent with autosomal recessive inheritance. This mutation Western blot analysis. The role of CXCR3 in gliadin-mediated was not identified in 200 ethnically matched control DNAs. zonulin release and intestinal transepithelial electrical resist- RT-PCR of duodenal tissue demonstrated a novel alternative ance (TEER) changes were studied ex vivo using C57BL/6 splice form with deletion of exon 4 in affected patients. Immu- wild-type (WT)–and CXCR3/–mouse small intestine in nohistochemistry of patient intestinal tissue revealed decreased microsnapwell assays, laser capture microdissection, rtRT- expression of EpCAM. Mutations in the gene for EpCAM are PCR, and immunohistochemistry. responsible for CTE. This information will be used to gain further Results: In vitro experiments showed specific co-localization of insight into the molecular mechanisms of this disease. gliadin with CXCR3. CXCR3 was expressed in intestinal epithelium and lamina propria (LP) and was up-regulated during active celiac disease (CD) but not after remission following 224 gluten-free diet (GFD). Gliadin exposure led to physical associ- BOTH INTERFERON-g AND INTERLEUKIN-17 ARE ation of CXCR3 with MyD88. Increased zonulin release and IMPLICATED IN DEXTRAN SULFATE / decreased TEER were detected in WT, but not in CXCR3 SODIUM-INDUCED COLITIS intestinal segments after gliadin exposure. Pre-incubation of WT Zili Zhang1,2, Wenwei Zhong1, Samphea Seng2, Keith gut tissue with G-coupled protein receptor inhibitor, pertussis Wegmann2, David Hinrichs2. 1Pediatrics, Oregon Health & toxin (PT), prevented the gliadin-induced drop in TEER (1.5%, Science University, Portland, OR; 2Immunology Research, P = NS) compared to media controls (33.5%, P = 0.034) and Veterans Affairs Medical Center, Portland. inactive genetic mutant of PT (31.2%, P =0.06). Conclusion: Gliadin binding to CXCR3 leads to activation of Objective: Interferon-g (IFN-g) is an important Th1 cytokine the zonulin pathway and IP increase in a MyD88- and for host defense, whereas interleukin-17 (IL-17) is produced by G-coupled protein receptor-dependent fashion. CXCR3 intes- Th17 cells in many inflammatory diseases. In fact, IFN-g is tinal expression was detected at epithelial and LP level and was found to suppress the development of Th17 cells. Our previous up-regulated during active CD but not after CD remission. study and others have shown that IL-17 is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, 223 the role of IFN-g in IBD is still unclear. Methods: In this study, we induced colitis with dextran sulfate MUTATION IN THE GENE FOR EPITHELIAL CELL sodium (DSS) in both wild-type and IFN-g knockout mice. Some ADHESION MOLECULE IS RESPONSIBLE FOR wild-type mice were treated with anti-IFN-g antibody, anti-IL-17 CONGENITAL TUFTING ENTEROPATHY antibody, or both antibodies during the experiment. The body Mamata Sivagnanam1, J. Mueller1, H. Lee2, Z. Chen2, weight of these mice was monitored daily as a marker of colitis S. Nelson2, O. Libiger4, N. Schork4, J. Lavine1, S. Taylor1, severity for 10 days. Histology and TNF-a were assessed in the R. Newbury5, R. Kolodner3, H. Hoffman1. 1Department of colons of these mice to assess the severity of colitis.

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Results: IFN-g knockout mice exhibited less weight loss and phorylation, and for PKC in feedback inhibition of the ERK colonic inflammation than wild-type mice. In addition, signal, which may potentially prevent uncontrolled mitogenic although anti-IFN-g or anti-IL-17 antibody alone did not signaling. alleviate the intestinal injury, the mice treated with both antibodies were protected from DSS-induced colitis. If the involve- 226 ment of IFN-g was to defend against gut bacterial invasion during the intestinal damage, we postulated that antibiotic THE ROLE OF TRAF2 AND TRAF6 IN CD40 treatment would attenuate the colitis in the mice only received SIGNALING IL-17-neutralizing therapy. Therefore, we treated mice daily Jason M. Ellison, Mikaela M. Tremblay, Bruce S. Hostager. with vancomycin and imipenem in conjunction of anti-IL-17 Pediatrics, University of Iowa Children’s Hospital, Iowa City. antibody. Although the antibiotics significantly altered the gut flora counts, they did not mitigate colonic inflammation. CD40, a member of the TNF receptor family, plays a central role Conclusions: Our data suggest that both IFN-g and IL-17 play a in regulating immunity and inflammation. CD40 signaling in direct role in DSS-induced colitis. It appears that bacterium- endothelial and immune cells also contributes to the pathogenesis mediated colonic inflammation is not a primary reason for the of inflammatory bowel disease (IBD). These properties make participation of IFN-g in the colitis. Thus, the mechanism of CD40 an attractive target for therapies directed at IBD. The IFN-g in the pathogenesis of IBD remains to be fully elucidated. cytoplasmic domain of CD40 interacts with several members of the TNF receptor-associated factor (TRAF) family, which link CD40 to intracellular signaling pathways. TRAFs 2 and 6 appear 225 to play particularly important roles in CD40 signaling. To better ANGIOTENSIN II-INDUCED MITOGENIC SIGNALING understand the roles of TRAF2 and TRAF6 in CD40 signaling, IN INTESTINAL EPITHELIAL CELLS: PROTEIN we used somatic cell gene targeting to create TRAF-deficient KINASE C (PKC) MEDIATES FEEDBACK INHIBITION mouse B cell lines. A20.2J cells deficient in TRAF6 exhibit OF ERK THROUGH EGFR TRANSACTIVATION marked defects in CD40-mediated Jun N-terminal kinase (JNK) Steven S. Wu1, Enrique Rozengurt2. 1Pediatrics, 2Medicine, activation and CD80 upregulation. Activation of nuclear factor University of California-Los Angeles. kappa-B (NF-kB) was intact in cells deficient in TRAF2 or TRAF6, but defective in cells lacking both TRAF2 and TRAF6. Interestingly, we found that a TRAF6 mutant lacking Background and Aim: Transactivation of the epidermal the domain necessary for CD40 binding was able to restore growth factor receptor (EGFR) has proven to be an important CD40-mediated NF-kB activation. We find that CD40 mechanism in cellular growth and differentiation, in particular mediated activation of transforming growth factor-activated through activation of the ERK1/2 members of the mitogen- kinase 1 (TAK1) is ablated when TRAF6 is absent. We are activated protein kinase family. In intestinal epithelial cells, further investigating other mitogen-activated protein kinases angiotensin II (Ang II) stimulates mitogenesis via EGFR trans- that may interact with TRAF2 or TRAF6 in propagating CD40 activation, and protein kinase C (PKC) mediates feedback mediated signals. Results of this work will contribute to the inhibition of EGFR. However, the mechanisms are complex development of novel methods for treating immune-mediated and not fully defined. The aim of this study was to examine the diseases such as inflammatory bowel disease. roles of EGFR and PKC in the Ang II-induced activation of ERK. Methods: Phosphorylation of activated ERK was measured by NASPGHAN-CDHNF Fellow to Faculty Transition Award immunoprecipitation and Western blotting with phosphospeci- in Inflammatory Bowel Diseases fic antibodies. IEC-18 intestinal epithelial cells were stimulated Histone Deacetylase Inhibition and Inflammatory Bowel with Ang II, epidermal growth factor (EGF), or the PKC agonist Disease. Edwin de Zoeten, MD, Children’s Hospital of phorbol dibutyrate. Selected cells were preincubated with Philadelphia inhibitors of PKC, EGFR, or Ca2+ signaling. Results: Ang II stimulated ERK phosphorylation by >50-fold HEPATIC, PANCREATIC, AND NUTRITIONAL over baseline, with a peak at 2.5 min, decreasing to half- DISORDERS maximal by 5 min. EGF stimulated ERK with a peak at 5 min. At 2.5 min of Ang II stimulation, ERK phosphorylation 227 was partially blocked by the EGFR kinase inhibitor AG1478, but not by PKC inhibition or Ca2+ depletion. However, ERK GENE MUTATIONS AND CLINICAL OUTCOME was strongly blocked by the combination of AG1478 with either AFTER BILIARY DIVERSION SURGERY FOR PKC or Ca2+ inhibition. When kinetics were examined further, INTRACTABLE PRURITUS IN CHILDREN WITH AG1478 completely blocked ERK at times >5 min, while PKC INTRAHEPATIC CHOLESTASIS inhibition with multiple PKC inhibitors led to increased ERK A. Miethke, U. Matte, C. Liu, W. Balistreri, F. Ryckman, J. phosphorylation between 5 and 60 min. If both EGFR and PKC Bezerra. Children’s Hospital Medical Center, Cincinnati, OH. were inhibited, ERK was blocked at all times. Conclusion: These results show that while either PKC or Background: The post-operative outcome of biliary diversion EGFR alone can activate ERK, Ang II-stimulated ERK (BD) surgery for refractory pruritus in children with cholestasis phosphorylation is suppressed at later times by PKC. Since is variable and poorly predictable. We hypothesized that PKC inhibits EGFR transactivation, our data supports key mutations in the ATP8B1, ABCB11, ABCB4, and JAG1 genes roles for both EGFR transactivation in sustained ERK phos- segregate with clinical response to BD.

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Methods: All exons and exon/intron boundaries for the 4 genes expression increased in all PN groups refuting the hypothesis were sequenced using the JaundiceChip in 14 children after BD. that these changes were due to decreased MTP-mediated The types of mutations were compared to post-operative hepatic lipoprotein assembly. FA synthase (FAS) was changes in pruritus and serum bile acid (SBA) levels upregulated and CPT1, a key gene in FAO, downregulated (follow-up: 21–44 mo). in PNA indicating increased FA synthesis and reduced FAO Results: Disease-causing mutations were found in 12 of 14 chil- similar to models of essential FA deficiency (EFAD). The dren. Six of them had low serum GGT, of which 5 were found to addition of IL decreased FAS and SREBP1c and decreased have disease-causing mutations in ATP8B1 or ABCB11. Pruritus TG synthesis genes (DGAT1,MGAT2), indicating that improved in 3 of these 5 children; 2 of 3 also had reduced SBA lipogenesis is no longer upregulated; but CPT1 downregula- following BD. These children had missense mutations or in- tion persisted with IL. SCD1, involved in synthesis of mono- frame deletions in ATP8B1, or a splice-site mutation in ABCB11, unsaturated FA added to VLDL particles prior to secretion, none of them predicted to prematurely terminate transcription. In was upregulated in PNA but dramatically downregulated in contrast, the 2 children without improvement had nonsense mice given IL. mutations in ATP8B1 and ABCB11, both predicted to generate Conclusions: Mice chronically fed PN without lipid develop truncated proteins. Of the 8 subjects with high GGT,7 had clinical steatosis similar to that seen in EFAD. Mice fed PN plus lipid and histological features of Alagille syndrome; 4 showed continue to show low plasma non-HDL lipoproteins and improvement in pruritus and 5 had reduced SBA after BD. increased hepatic lipids; not due to increased lipogenesis or Disease-causing heterozygous mutations in JAG1 were detected decreased MTP-dependent lipoprotein assembly. Apart from in all 7 subjects, but the type of mutations did not segregate with decreased FAO, other potential mechanisms include reduced different post-surgical outcome groups. All 3 subjects with poor VLDL secretion or increased plasma lipoprotein clearance. outcome also had nonsynonymous mutations in ATP8B1 or ABCB11. Conclusions: 1) Nonsense mutations in ATP8B1 or ABCB11 229 were present in children with low GGT and poor response to INFANT NUTRITION AND RISK OF CELIAC DISEASE BD, and 2) the JAG1 mutations in children with (CD): PILOT INTERVENTION, PROSPECTIVE, Alagille syndrome did not segregate with types of clinical MULTICENTER STUDY response, but children with poor outcome harbored coexisting S. Kulpuru, D. Kryszak, C. Catassi, A. Fasano. Center for nonsynonymous mutations in ATP8B1 or ABCB11. Validation Celiac Research, University of Maryland School of Medicine, of these findings in a larger cohort will determine whether Baltimore. surgical treatment for intractable pruritus can be tailored to the patient’s genetic makeup. Background: Despite the significant progress made in under- AM is funded by the Cholestatic Liver Disease Consortium. standing the adaptive immunological aspects of celiac disease (CD) pathogenesis, the early steps following exposure to gliadin 228 leading to loss of tolerance and development of the autoimmune process are still largely unknown. Recent retrospective PATHOGENESIS OF HEPATIC LIPID DEPOSITION IN studies suggest that dysfunctional cross talk between innate A MOUSE MODEL OF PARENTERAL NUTRITION and adaptive immunity can be influenced by the timing of ASSOCIATED LIVER DISEASE (PNALD) gluten introduction in the diet of subjects genetically suscept- Farrah Lazare, Jahangir Iqbal, Sujai Jalaj, Xiaoyue Pan, Miguel ible to CD. Guzman, Virginia Anderson, M. Mahmood Hussain, William R. Aim: To study the role of timing of gluten introduction in early Treem. SUNY Downstate School of Medicine, Brooklyn. steps involved in the onset of CD in genetically-predisposed infants. Background: PNALD is characterized by steatohepatitis, Methods: Infants less than 6 months of age who were on cholestasis, and fibrosis. Recent attention centers on the role exclusive milk diet (breast milk or formula) and who were (a) of lipid emulsions. first-degree relatives of patients affected with biopsy-proven CD Aims: To understand mechanisms of steatosis in a mouse model and (b) positive for HLA-DQ2 and/or DQ8 genotypes were of PN without lipid, with enteral, and with parenteral lipid. enrolled. From weaning (4 to 6 months of age) to 12 months Methods: 4 groups of 5 wk C57BL/6J mice (n = 5/group) were the enrolled children were randomized in a double blind fashion fed either mouse chow (C); oral PN alone (20% dextrose, 2% to a gluten free diet (GFD) supplemented with either gluten aa) (PNA); oral PN plus intraperitoneal 20% Intralipid (IL) (group A) or starch (group B). Subsequently, children went on an q.o.d. (PNILP); or oral PN plus gavage 20% IL q.o.d. (PNILG). unrestricted diet and periodically checked for onset of symptoms At 19 d, plasma and tissue triglyceride (TG) and cholesterol; and CD serology. hepatic microsomal TG transfer protein (MTP); liver histology; Results: A total of 516 infants (249 females) have been and gene expression involved in fatty acid (FA) synthesis, FA enrolled. At age 15 months follow up, 5 of 121 (4%) infants oxidation (FAO), and TG synthesis using RT-PCR were in group A tested positive for anti-tissue transglutaminase assessed. antibodies (TTG), while none of the 84 infants enrolled in Results: Wt gain was equal except for slight increase in group B tested TTG positive. At the 24 months of age follow up, PNILG. Steatosis was evident in all PN groups, especially an additional 5 children in group A tested TTG positive, while PNA. Plasma TG decreased in all PN groups, predominantly all children in group B remained TTG-negative. All TTG- the non-HDL TG. Hepatic TG increased in all PN groups, positive children that underwent to an intestinal biopsy showed most significantly in PNA. MTP activity, synthesis, and gene mucosal damage typical of CD.

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Conclusions: Our preliminary data suggest that gluten intro- TABLE 1. duction within the second semester of life in genetically Ratio of eos/T84 0.01 0.03 0.3 susceptible individuals cause early onset of CD. Prolonged Eosinophils 7 14 38 18 51 12 follow up is necessary to establish whether delayed introduction Beads 4 18 12 14 16 14 of gluten merely delay the onset of the disease or truly prevents CD by inducing gluten tolerance. Expressed as % change in TER from baseline. George Ferry Young Investigator Award

Mitochondrial SCHAD in Hyperinsulinism and Hepatic Steatosis. Lynette Gillis, MD, Vanderbilt University, TABLE 2. Nashville, TN Ratio of eos/T84 0.0 0.01 0.03 0.1 0.3 CDHNF Young Investigator Development Award Hemado (A3 Agonist) 21 2 25 2 1 4 6 32 4 Mechanisms of Bile Duct Proliferation in Mice Heterozygous Adenosine 39 2 15 0 19 1 12 66 7 for JAG1 and Fringe Genes. Matthew Ryan, MD, Children’s Expressed as % change in TER from baseline. Hospital of Philadelphia CDHNF Young Investigator Development Award Ryanodine Receptor Calcium Flux in Pancreatitis. Sohail 231 Husain, MD, Yale University Medical Center, New Haven, CT POSTNATAL ACQUISITION OF COMMENSAL MICROBIOTA IN THE DEVELOPMENT OF IMMUNE PEDIATRIC INFLAMMATORY DISORDERS FUNCTION Reed A. Dimmitt1,2, Elizabeth M. Staley2, Robin G. Lorenz2,3. 1 2 3 230 Pediatrics, Microbiology, Pathology, University of Alabama at Birmingham. EOSINOPHILS ENHANCE INTESTINAL EPITHELIAL BARRIER Vincent A. Mukkada1,2, Sean P. Colgan2, Glenn T. Furuta1,2. Background: The sterile newborn intestine is rapidly colonized 1Pediatric Gastroenterology and Hepatology Section, by bacteria, resulting in both defense and tolerance. We set out Children’s Hospital Denver, Denver, CO; 2University of to determine the role of bacteria to shape the early postnatal Colorado Health Sciences Center, Denver. immune development. Methods: Specific pathogen free (SPF) C57BL/6 mice were sacrificed at E20.5, and postnatal day 3, 7, 14, 21, Background: Eosinophils normally reside adjacent to epi- and 42 (6 weeks). RNA was extracted from the GI tract for thelial surfaces but their role in GI health is uncertain. Recent real-time PCR analysis of gene expression. Separate studies implicate leukocyte nucleosides (adenosine) as regulat- dams were bred in SPF or microbial reduced (MR) conditions ory molecules in cell-cell interactions. Adenosine 1,2a,2b but (antibiotic treated drinking water). Pups were sacrificed at 2 not A3 receptors are present on epithelia; eosinophils possess weeks and GI tract immune molecule expression analyzed. cell surface A3 receptors. Additional2weekoldSPFandMRpupswereorally Hypothesis: Eosinophils contribute to intestinal health by inoculated with GFP producing E. coli to determine barrier protecting intestinal barrier function. function by culturing mesenteric lymph nodes, liver, and Aim: To determine eosinophil’s impact on epithelial barrier spleen. T-cell phenotype from 2 week old SPF and MR function. was determined by FACS. T-cells were also cultured with Methods: Various ratios of T84 colonic epithelial cells and anti-CD3 monoclonal antibody for cytokine production, AML14.3D10 eosinophils (eos) were grown in contact determined by ELISA. co-culture (0.01 eos/T84 to 0.3 eos/T84). Barrier function was assessed by transepithelial resistance (TER) measurement and Results: When normalized to E20.5, expression of toll-like response to adenosine stimulation. receptors (TLR) 2, 4, 5, and 9 and IL-8 like chemokines was Results: The presence of eos increased epithelial barrier in a significantly greater at 2 weeks of age but was attenuated by concentration dependent manner (Table 1: P < 0.02, ANOVA). 6 weeks in SPF pups. This increase in TLR and chemokine Co-cultures of T84 cells with inert beads (equivalent size of eos) expression was not seen in the MR pups. There was more did not increase barrier (Table 1). As a measure of acute expression of pro-inflammatory cytokines in the MR mice, in epithelial function, co-cultures were stimulated with adenosine particular colonic IL-6, IL-12, and IL-23. The MR pups had (A1, A2a, A2b, A3 receptor agonist) or Hemado (selective A3 GFP E. coli translocation to all 3 organs while the SPF pups had agonist). Hemado stimulation increased barrier function no positive cultures. There was no difference in the number or significantly relative to adenosine stimulation (Table 2: phenotype of splenic T-cells by FACS. SPF T-cells had greater P < 0.01 Hemado vs. adenosine, t test). Supernatant from production of IFN-g and IL-17 while the MR had more IL-4 and T84/eos co-cultures applied to na¨ıve monolayers led in an IL-10. increase in TER similar to that seen with co-culture Conclusion: Neonates that fail to acquire commensal bacteria (23 7% vs. 5 4%, P < 0.01; adenosine vs. media). have an altered systemic and mucosal immune function. This Conclusions: Eosinophils increase epithelial barrier function. skewed postnatal immunity could explain the role of probiotics Stimulation of the eosinophil A3 receptor enhances this in necrotizing enterocolitis (NEC). Determining the specific increase in barrier. A soluble eosinophil derived product may bacteria and signaling mechanism could provide a focused account for this finding. therapeutic intervention to prevent NEC.

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TABLE 1. Summary of Results Total Total cases bacterial Intussusceptions Intussusception test group Odds ratio 95% conﬁdence intervals children enteritis following infections

All infections, Age 0–5; 0–180 days PI 40.56 28.62–57.48 387,514 1412 37 All infections, Age <1; 0–180 days PI 16.07 9.15–28.22 54,927 426 14 All infections Age 1–5; 0–180 days PI 56.15 35.97–87.63 332,587 986 23 All infections, Age 0–5; 0–60 days PI 19.21 12.03–30.66 387,514 1412 19 All infections, Age 0–5; 60–120 days PI 8.71 4.48–16.96 387,514 1412 9 All infections, Age 0–5; 120–180 days PI 8.71 4.48–16.96 387,514 1412 9 Salmonella sp, Age 0–5; 0–180 days PI 46.96 28.93–76.21 387,514 557 18 E coli, Age 0–5; 0–180 days PI 33.30 18.56–59.73 387514 496 12 Shigella sp, Age 0–5; 0–180 days PI 24.43 10.01–59.60 387,514 280 5 Campylobacter, Age 0–5; 0–180 days PI 43.42 10.62–179.23 387,514 63 2

232 Results: Intussusceptions significantly followed Salmonella, E coli, Shigella, and Campylobacter, in this order. No intus- BACTERIAL ENTERITIS, A RISK FACTOR FOR susceptions followed Yersinia infections, possibly due to low CHILDHOOD INTUSSUSCEPTIONS numbers (4 cases). Results summarized in Table 1. Cade M. Nylund, James Noel. Pediatrics, San Antonio Military Conclusion: Bacterial enteritis is a significant risk factor Pediatric Center, San Antonio, TX. for subsequently developing intussusception in children. Within our study there is a higher risk of intussuscep- Background: Few studies address the relationship between tion within the first 60 days after infection, in patients bacterial enteritis and intussusception. Bacterial enteritis may 1–5 years old, and is most prominent after Salmonella induce lymphoid hyperplasia which may serve as the lead point infections. for subsequent intussusception. Methods: The Patient Administration Systems and Biosta- tistics Activity database was examined for clinic visits CDHNF Young Investigator Development Award or hospital admission to a Department of Defense (DoD) A Protective Role for GSK-3b During Initiation of Inflammatory medical facility from Jan 2002 to Dec 2005 for children age Bowel Disease. Kris Steinbrecher, MD, Cincinnati Children’s 0–5 years old and the ICD diagnosis related group (DRG) Hospital Medical Center codes for infection with: Yersinia enterocolitica, Escherichia CDHNF/Nestle´ Nutrition Award for Young Investigators coli, Shigella species, Salmonella species, and Campylobac- Optimization of Vitamin D Status and Its Effects on Bone Health ter. Identified patients were then checked for the DRG codes and Disease Outcomes in Children and Adolescents With or current procedural terminology (CPT) codes for intussus- Inflammatory Bowel Disease. Helen Pappa, MD, Children’s ception during 0–180 days post-infection (PI). The total Hospital Boston number of children enrolled in military treatment facilities CDHNF/Crohn’s and Colitis Foundation of America IBD in same age group (denominator) was obtained. The total Grant for New Investigators numbers of DRG/CPT codes for unique patients with intus- Gender Differences in Growth in Pediatric Patients With susceptions and respective intestinal infections were also Crohn’s Disease. Neera Gupta, MD, University of California, obtained. San Francisco

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