Journal of Pediatric Gastroenterology and NutritionVolume 66, Issue S1 p. S54-S54 Supplement Chapter 5. Fifty Years of Paediatric Gastroenterology Olivier Goulet, Corresponding Author Olivier Goulet [email protected] Divison of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, University Cité-Paris Sorbonne, Paris Descartes Medical School, Paris, FranceAddress correspondence and reprint requests to Olivier Goulet, MD, PhD, Hôpital Necker University of Paris Descartes, Paris, France (e-mail: [email protected]).Search for more papers by this authorRicardo Troncone, Ricardo Troncone Department of Translational Medical Sciences, European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University of Naples Federico II, Naples, ItalySearch for more papers by this authorMarku Makki, Marku Makki Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, FinlandSearch for more papers by this authorJacques Schmitz, Jacques Schmitz Hôpital Necker-Enfants malades, University Paris-Descartes, Paris, FranceSearch for more papers by this authorIsabel Polanco, Isabel Polanco Facultad de Medicina, Universidad Autónoma de Madrid, SpainSearch for more papers by this authorMaria Luisa Mearin, Maria Luisa Mearin Department of Pediatrics, Leiden University Medical Center, Leiden, The NetherlandsSearch for more papers by this authorSamy Cadranel, Samy Cadranel Queen Fabiola Children's Hospital, Free University of Brussels, BelgiumSearch for more papers by this authorSibylle Koletzko, Sibylle Koletzko Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, GermanySearch for more papers by this authorGiuseppina Oderda, Giuseppina Oderda Università del Piemonte Orientale, Novara, ItalySearch for more papers by this authorAlan Phillips, Alan Phillips UCL Emeritus Professor of Paediatric Gastroenterology, UCL Medical School, London, UKSearch for more papers by this authorSimon Murch, Simon Murch Warwick University, London, UK University Hospital Coventry & WarwickshireSearch for more papers by this authorJohn Walker-Smith, John Walker-Smith University of London, London, UKSearch for more papers by this authorFrank Ruemmele, Frank Ruemmele Necker Enfants Malades Hospital, Pediatric Gastroenteroloy, Université Paris Descartes—Sorbonne Paris Centre, Paris, FranceSearch for more papers by this authorJorge-Amil Dias, Jorge-Amil Dias Hospital S. João, University of Porto, PortugalSearch for more papers by this authorSanja Kolacek, Sanja Kolacek University Department of Pediatrics, Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital, Zagreb, CroatiaSearch for more papers by this authorYigael Finkel, Yigael Finkel Department of Gastroenterology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorJohn Puntis, John Puntis Leeds Teaching Hospitals NHS Trust, London, UKSearch for more papers by this authorAntonella Diamanti, Antonella Diamanti Artificial Nutrition Unit, “Pediatric Hospital Bambino Gesù,”, Rome, ItalySearch for more papers by this authorSusan Hill, Susan Hill Department of Paediatric Gastroenterology, Great Ormond Street Hospital NHS Foundation Trust, London, UKSearch for more papers by this authorFlorence Lacaille, Florence Lacaille Department of Paediatric Gastroenterology-Hepatology-Nutrition, National Reference Center for Rare Digestive Disease, Reference Center for Home Parenteral Nutrition, Hôpital Necker Enfants Malades, Paris, FranceSearch for more papers by this authorGirish Gupte, Girish Gupte XXXSearch for more papers by this authorJean Francois Mougenot, Jean Francois Mougenot Hospitals Robert Debré and Necker-Enfants Malades, AP Paris, FranceSearch for more papers by this authorMike Thompson, Mike Thompson Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UKSearch for more papers by this authorMarc Benninga, Marc Benninga Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Centre, Amsterdam, The NetherlandsSearch for more papers by this authorNikhil Thapar, Nikhil Thapar Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UKSearch for more papers by this authorAnnamaria Staiano, Annamaria Staiano Department of Translational Medical Science, Section of Paediatrics, University of Naples Federico II, Naples, ItalySearch for more papers by this authorGigi Veereman, Gigi Veereman Pediatric Gastroenterology and Nutrition, University Hospital Brussels, Free University Brussels, BelgiumSearch for more papers by this authorYvan Vandenplas, Yvan Vandenplas Department of Pediatrics, UZ Brussel, Vrije Universiteit Brussel, Brussels, BelgiumSearch for more papers by this authorPeter Milla, Peter Milla Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UKSearch for more papers by this authorJehan-François Desjeux, Jehan-François Desjeux Académie nationale de médecine, Paris, FranceSearch for more papers by this authorAlfredo Guarino, Alfredo Guarino Department of Translational Medical Science, Section of Pediatrics University of Naples Federico II, Naples, ItalySearch for more papers by this authorHania Szajewska, Hania Szajewska Department of Paediatrics, The Medical University of Warsaw, Warsaw, PolandSearch for more papers by this author Olivier Goulet, Corresponding Author Olivier Goulet [email protected] Divison of Pediatric Gastroenterology-Hepatology-Nutrition, Hôpital Necker-Enfants Malades, University Cité-Paris Sorbonne, Paris Descartes Medical School, Paris, FranceAddress correspondence and reprint requests to Olivier Goulet, MD, PhD, Hôpital Necker University of Paris Descartes, Paris, France (e-mail: [email protected]).Search for more papers by this authorRicardo Troncone, Ricardo Troncone Department of Translational Medical Sciences, European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University of Naples Federico II, Naples, ItalySearch for more papers by this authorMarku Makki, Marku Makki Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, FinlandSearch for more papers by this authorJacques Schmitz, Jacques Schmitz Hôpital Necker-Enfants malades, University Paris-Descartes, Paris, FranceSearch for more papers by this authorIsabel Polanco, Isabel Polanco Facultad de Medicina, Universidad Autónoma de Madrid, SpainSearch for more papers by this authorMaria Luisa Mearin, Maria Luisa Mearin Department of Pediatrics, Leiden University Medical Center, Leiden, The NetherlandsSearch for more papers by this authorSamy Cadranel, Samy Cadranel Queen Fabiola Children's Hospital, Free University of Brussels, BelgiumSearch for more papers by this authorSibylle Koletzko, Sibylle Koletzko Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, GermanySearch for more papers by this authorGiuseppina Oderda, Giuseppina Oderda Università del Piemonte Orientale, Novara, ItalySearch for more papers by this authorAlan Phillips, Alan Phillips UCL Emeritus Professor of Paediatric Gastroenterology, UCL Medical School, London, UKSearch for more papers by this authorSimon Murch, Simon Murch Warwick University, London, UK University Hospital Coventry & WarwickshireSearch for more papers by this authorJohn Walker-Smith, John Walker-Smith University of London, London, UKSearch for more papers by this authorFrank Ruemmele, Frank Ruemmele Necker Enfants Malades Hospital, Pediatric Gastroenteroloy, Université Paris Descartes—Sorbonne Paris Centre, Paris, FranceSearch for more papers by this authorJorge-Amil Dias, Jorge-Amil Dias Hospital S. João, University of Porto, PortugalSearch for more papers by this authorSanja Kolacek, Sanja Kolacek University Department of Pediatrics, Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital, Zagreb, CroatiaSearch for more papers by this authorYigael Finkel, Yigael Finkel Department of Gastroenterology, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorJohn Puntis, John Puntis Leeds Teaching Hospitals NHS Trust, London, UKSearch for more papers by this authorAntonella Diamanti, Antonella Diamanti Artificial Nutrition Unit, “Pediatric Hospital Bambino Gesù,”, Rome, ItalySearch for more papers by this authorSusan Hill, Susan Hill Department of Paediatric Gastroenterology, Great Ormond Street Hospital NHS Foundation Trust, London, UKSearch for more papers by this authorFlorence Lacaille, Florence Lacaille Department of Paediatric Gastroenterology-Hepatology-Nutrition, National Reference Center for Rare Digestive Disease, Reference Center for Home Parenteral Nutrition, Hôpital Necker Enfants Malades, Paris, FranceSearch for more papers by this authorGirish Gupte, Girish Gupte XXXSearch for more papers by this authorJean Francois Mougenot, Jean Francois Mougenot Hospitals Robert Debré and Necker-Enfants Malades, AP Paris, FranceSearch for more papers by this authorMike Thompson, Mike Thompson Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UKSearch for more papers by this authorMarc Benninga, Marc Benninga Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Centre, Amsterdam, The NetherlandsSearch for more papers by this authorNikhil Thapar, Nikhil Thapar Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UKSearch for more papers by this authorAnnamaria Staiano, Annamaria Staiano Department of Translational Medical Science, Section of Paediatrics, University of Naples Federico II, Naples, ItalySearch for more papers by this authorGigi Veereman, Gigi Veereman Pediatric Gastroenterology and Nutrition, University Hospital Brussels, Free University Brussels, BelgiumSearch for more papers by this authorYvan Vandenplas, Yvan Vandenplas Department of Pediatrics, UZ Brussel, Vrije Universiteit Brussel, Brussels, BelgiumSearch for more papers by this authorPeter Milla, Peter Milla Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UKSearch for more papers by this authorJehan-François Desjeux, Jehan-François Desjeux Académie nationale de médecine, Paris, FranceSearch for more papers by this authorAlfredo Guarino, Alfredo Guarino Department of Translational Medical Science, Section of Pediatrics University of Naples Federico II, Naples, ItalySearch for more papers by this authorHania Szajewska, Hania Szajewska Department of Paediatrics, The Medical University of Warsaw, Warsaw, PolandSearch for more papers by this author First published: 01 April 2018 https://doi.org/10.1002/j.1536-4801.2018.tb00037.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Journal of Pediatric Gastroenterology and NutritionVolume 66, Issue S1 p. S65-S67 Supplement Chapter 5.1.3. Forty Years of Helicobacter Pylori in ESPGHAN Samy Cadranel, Samy CadranelSearch for more papers by this authorGiuseppina Oderda, Giuseppina OderdaSearch for more papers by this authorSibylle Koletzko, Sibylle KoletzkoSearch for more papers by this author Samy Cadranel, Samy CadranelSearch for more papers by this authorGiuseppina Oderda, Giuseppina OderdaSearch for more papers by this authorSibylle Koletzko, Sibylle KoletzkoSearch for more papers by this author First published: 01 April 2018 https://doi.org/10.1002/j.1536-4801.2018.tb00041.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1.Figura N, Oderda G. Reflections on the first description of the presence of Helicobacter species in the stomach of mammals. Helicobacter 1996; 1: 4–5. 10.1111/j.1523-5378.1996.tb00002.x CASPubMedWeb of Science®Google Scholar 2.Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984; 1: 1311–1315. 10.1016/S0140-6736(84)91816-6 CASPubMedWeb of Science®Google Scholar 3.Cadranel S, Goossens H, De Boeck M, et al. Campylobacter pyloridis in children. Lancet 1986; 1: 735–736. 10.1016/S0140-6736(86)91120-7 CASPubMedWeb of Science®Google Scholar 4.Drumm B, Sherman P, Cutz E, et al. Association of Campylobacter pylori on the gastric mucosa with antral gastritis in children. N Engl J Med 1987; 6: 1557–1561. 10.1056/NEJM198706183162501 Google Scholar 5.Oderda G, Vaira D, Holton J. Age-related increase of Helicobacter pylori frequency in symptom-free and dyspeptic children. Lancet 1992; ii: 671–672. 10.1016/0140-6736(92)92204-S Google Scholar 6.Megraud F. Comparison of non-invasive tests to detect Helicobacter pylori infection in children and adolescents: results of a multicenter European study. J Pediatr 2005; 146: 198–203. 10.1016/j.jpeds.2004.10.044 PubMedWeb of Science®Google Scholar 7.Koletzko S, Richy F, Bontems F, et al. Prospective multicenter study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe. Gut 2006; 55: 1711–1716. 10.1136/gut.2006.091272 CASPubMedWeb of Science®Google Scholar 8.Kalach N, Bontems P, Koletzko S, et al. Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study. Eur J Gastroenterol Hepatol 2010; 22: 1174–1181. 10.1097/MEG.0b013e32833d36de PubMedWeb of Science®Google Scholar 9.Bontems P, Kalach N, Vanderpas J, et al. Helicobacter pylori Infection in European children with gastro-duodenal ulcers and erosions. Pediatr Infect Dis J 2013; 32: 1324–1329. 10.1097/INF.0000000000000005 PubMedWeb of Science®Google Scholar 10.Oderda G, Shcherbakov P, Bontems P, et al. Results from the pediatric European register for treatment of Helicobacter pylori (PERTH). Helicobacter 2007; 12: 150–156. 10.1111/j.1523-5378.2007.00485.x CASPubMedWeb of Science®Google Scholar 11.Khurana R, Fischbach L, Chiba N, et al. Meta-analysis of Helicobacter pylori eradication treatment efficacy in children. Aliment Pharmacol Ther 2007; 25: 523–536. 10.1111/j.1365-2036.2006.03236.x CASPubMedWeb of Science®Google Scholar 12.Schwarzer A, Urruzuno P, Iwanczak B, et al. New effective treatment regimen for children infected with a double-resistant Helicobacter pylori strain. J Pediatr Gastroenterol Nutr 2011; 52: 424–428. 10.1097/MPG.0b013e3181fc8c58 CASPubMedWeb of Science®Google Scholar 13.Francavilla R, Lionetti E, Castellaneta SP, et al. Improved efficacy of 10-Day sequential treatment for Helicobacter pylori eradication in children: a randomized trial. Gastroenterology 2005; 129: 1414–1419. 10.1053/j.gastro.2005.09.007 CASPubMedWeb of Science®Google Scholar 14.Bontems P, Kalach N, Oderda G, et al. Sequential therapy versus tailored triple therapies for Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr 2011; 53: 646–650. 10.1097/MPG.0b013e318229c769 CASPubMedWeb of Science®Google Scholar 15.Schwarzer A, Bontems P, Urruzuno P, et al. Sequential therapy for Helicobacter pylori infection in treatment-naive children. Helicobacter 2016; 21: 106–113. 10.1111/hel.12240 CASPubMedWeb of Science®Google Scholar 16.Jones N, Koletzko S, Goodman KJ, et al. Joint ESPGHAN /NASPGHAN guidelines for the management of Helicobacter pylori in children and adolescents (update 2016). J Pediatr Gastroenterol Nutr 2017; 64: 991–1003. 10.1097/MPG.0000000000001594 PubMedWeb of Science®Google Scholar 17.Drumm B, Koletzko S, Oderda G. Helicobacter pylori infection in children: a consensus statement. European Paediatric Task Force on Helicobacter pylori. J Pediatr Gastroenterol Nutr 2000; 30: 207–213. 10.1097/00005176-200002000-00020 CASPubMedWeb of Science®Google Scholar 18.Gold BD, Colletti RB, Abbott M, et al. Helicobacter pylori infection in children: recommendations for diagnosis and treatment. J Pediatr Gastroenterol Nutr 2000; 31: 490–497. 10.1002/j.1536-4801.2000.tb07169.x CASPubMedWeb of Science®Google Scholar 19.Jones NL, Sherman P, Fallone CA, et al. Canadian Helicobacter Study Group Consensus Conference: update on the approach to Helicobacter pylori infection in children and adolescents--an evidence-based evaluation. 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was negative effect on eradication rates. Conclusions : Japanese is below Westerners in the ratio of homo-EM. In this study, eradication rate was relatively low(70.2%) because of very high CAM-resistant rate(47.9%) , : the eradication rate of CAM-sensitive was very high(96.8%). In first line therapy, the EPZ based triple therapy is useful for the eradication of H pylori as well as RPZ based triple therapy without relation to CYP2C19 genotype, in Japan. Eradication rates

BACKGROUND The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens. OBJECTIVES The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events. SEARCH METHODS The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search. SELECTION CRITERIA Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded. DATA COLLECTION AND ANALYSIS Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori. MAIN RESULTS In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H₂RA) bismuth quadruple therapy (n = 3), H₂RA bismuth-based triple therapy (n = 2), H₂RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H₂RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data. AUTHORS' CONCLUSIONS Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.

Eosinophilic Oesophagitis (EO) is characterised by large numbers of eosinophils in oesophageal mucosa in response to food or inhaled antigens. Treatment with elimination diet or corticosteroids lead to improvement in some children, but their efficacy is not optimal. Aim of this study is to identify clinical, endoscopic and/or histological features associated with response to treatment with swallowed fluticasone propionate. Patients and methods In the last 12 years 34 children (M/F 25/9) with EO were treated with fluticasone propionate spray 250 μg/puff by inhaler without spacer, three puffs three times a day for 6 weeks, and returned for a follow-up endoscopy. At histology 25 of them were found to be responders to therapy (73.5%) and 9 were non-responders. Anthropometric characteristics, symptoms at presentation, endoscopic and histological data at baseline between responders and non-responders were compared. Results Age, sex, height, duration and type of main symptom at presentation, type of allergy and number of allergens, peripheral eosinophil counts an serum IgE were similar in responders and non-responders. At baseline histology findings responders had a more severe inflammation: median peak eosinophils/high power field was higher (76 vs 44 in non responders p=0.04), eosinophilic microabscesses were present in a significantly higher number of responders (p=0.04) and peak mast cells/ high power field was significantly higher (p=0.001). Conclusions Clinical characteristics of children with EO at baseline were similar in responders and non-responders, but a more severe inflammation in oesophageal mucosa was associated with a higher response rate to fluticasone treatment.

Background: To analyze risk factors associated with gastro-duodenal ulcers and erosions in children. Methods: Open, prospective, multicenter, case-control study carried out in 11 European countries in patients with gastric or duodenal ulcers/erosions and 2 age-matched controls each. Possible risk factors were recorded. Logistic regression models were performed with adjustment for centers and age groups. Results: Seven-hundred thirty-two patients (244 cases, 153 with erosions only and 91 with ulcers, and 488 controls) were recruited. Children receiving antimicrobials or acid suppressive drugs before endoscopy were excluded (202 cases/390 controls remained for risk factor analysis). Helicobacter pylori was detected more frequently in cases than controls but only in 32.0% versus 20.1% in controls (P = 0.001). Independent exposure factors for gastric ulcers were male gender (P = 0.001), chronic neurologic disease (P = 0.015), chronic renal disease (P < 0.001) and nonsteroidal anti-inflammatory drug consumption (P = 0.035). Exposure factors for duodenal ulcers were H. pylori infection (P < 0.001) and steroid consumption (P = 0.031). Chronic renal disease was the only independent factor associated with gastric erosions (P = 0.026), those associated with duodenal erosions being H. pylori infection (P = 0.023), active smoking (P = 0.006) and chronic arthritis (P = 0.008). No risk factor was identified in 97/202 (48.0%) cases. Conclusions: H. pylori remains a risk factor for duodenal, but not for gastric lesions in children in countries with low prevalence of infection. No risk factor could be identified in half of the children with gastro-duodenal ulcers/erosions.

Figure 1.Prevalence (in %) of the 5 most common gastric histopathologic findings in 575,895 controls (left columns) and 3,040 patients with gastroparesis (right columns).Significant odds ratios (with 95% confidence intervals) are depicted on top of the columns; n.s.

Objective: The aim of this study was to evaluate performance of serum antibodies against deamidated gliadin peptides (a-DGPs) in detecting compliance with gluten-free diet (GFD) in children with celiac disease (CD).Patients and Methods: Serum samples were collected the same day of endoscopy in 95 children with CD and 106 controls. We preliminarily calculated the cutoff of a-DGP immunoglobulin A (IgA) and a-DGP IgA+G in our population by receiver operating characteristic (ROC) curves. Of 95 children with CD, 28 were studied during the first year after GFD introduction, with interview and serum collection every 3 months. In addition, serum samples were collected in 106 children with CD on GFD for more than 1 year (range 1-14). In both groups of children with CD on GFD, we compared a-DGP IgA and IgA+G performance in monitoring compliance with GFD with anti-tissue transglutaminase antibodies (anti-tTG) IgA and anti-gliadin antibody (AGA) IgA.Results: The cutoff resulted in 13.1 arbitrary units (AU) for a-DGP IgA (sensitivity 87.4, 95% confidence interval [CI] 79%-92%, specificity 97.2, 95% CI 92%-99%) and 16.5 for a-DGP IgA+G (sensitivity 94.7, 95% CI 88%-98%, specificity 89.6, 95% CI 84%-95%). In the first year of GFD, at 6 to 8 months prevalence of positive a-DGPs was significantly higher in partially versus strictly compliant children, and at 9 to 12 months only prevalence of positive a-DGP IgA+G remained significantly higher. Moreover, at 9 to 12 months sensitivity to detect transgressions to GFD was 44% for a-DGP IgA and 100% for a-DGP IgA+G (P - 0.03). In the 106 children on GFD for more than 1 year, sensitivity to detect transgressions to GFD was 60% for a-DGP IgA and 76% for a-DGP IgA+G. Anti-tTG IgA and AGA IgA sensitivity was much lower (24% and 4%, respectively). The 4 tests showed comparable high specificity.Conclusions: Both a-DGPs showed higher sensitivity than anti-tTG IgA and AGA IgA in monitoring compliance with GFD, but a-DGP IgA+G seemed to perform better. a-DGPs did not outperform anti-tTG IgA for CD screening.

Objective: As the clinical implications of Helicobacter pylori infection in children and adolescents continue to evolve, ESPGHAN and NASPGHAN jointly renewed clinical guidelines using a standardized evidence-based approach to develop updated recommendations for children and adolescents in North America and Europe.Methods: An international panel of 11 pediatric gastroenterologists, 2 epidemiologists, 1 microbiologist, and 1 pathologist was selected by societies that developed evidence-based guidelines based on the Delphi process with anonymous voting in a final face-to-face meeting. A systematic literature search was performed on 8 databases of relevance including publications from January 2000 to December 2009. After excluding nonrelevant publications, tables of evidence were constructed for different focus areas according to the Oxford classification. Statements and recommendations were formulated in the following areas: whom to test, how to test, whom to treat, and how to treat. Grades of evidence were assigned to each recommendation based on the GRADE system.Results: A total of 2290 publications were identified, from which 738 were finally reviewed. A total of 21 recommendations were generated, and an algorithm was proposed by the joint committee providing evidence-based guidelines on the diagnostic workup and treatment of children with H pylori infection.Conclusions: These clinical practice guidelines represent updated, best-available evidence and are meant for children and adolescents living in Europe and North America, but they may not apply to those living on other continents, particularly in developing countries with a high H pylori infection rate and limited health care resources.

L’« Enquête patients soins et intervenants de la douleur neuropathique » (Epsidone) a été menée via le réseau Internet pour préciser le parcours de soins et les modalités de prise en charge des patients souffrant de douleurs neuropathiques chroniques. Le questionnaire Epsidone a été mis en ligne sur le site médical grand public Doctissimo© pendant une période de cinq mois. Seules les personnes majeures, résidant en France, souffrant de douleurs chroniques (d’une durée de plus de trois mois) ayant des caractéristiques neuropathiques détectées au moyen du questionnaire DN4, pouvaient accéder à l’ensemble du questionnaire. Près de 2000 réponses ont été obtenues entre avril et août 2008 (78 % de femmes, âgées de 30 à 60 ans dans 74 % des cas). Les trois quarts (74 %) des participants souffraient de douleurs intenses ou insupportables, qui étaient présentes depuis plus de deux ans dans 60 % des cas. Ces douleurs étaient le plus souvent localisées dans le dos (76 %) et/ou les jambes (70 %). Les principales causes de douleur étaient : hernie discale (22,7 % des réponses), discopathies (16 %), intervention chirurgicale (9,3 %), lésion nerveuse périphérique (9,3 %) et syndrome douloureux régional complexe (6,7 %). Outre le médecin traitant (68,5 % des cas), ces douleurs ont motivé des consultations auprès d’autres professionnels de santé (plus de cinq différents dans 24 % des cas). Près de la moitié (47 %) des répondants ignoraient l’existence de consultations spécialisées dans le traitement des douleurs et 78 % des personnes connaissant leur existence ne savaient pas localiser la plus proche de chez eux. Plus de 43 % des répondants ont déclaré ne prendre aucun traitement pour leurs douleurs. Pour les 57 % de patients traités, les traitements les plus utilisés étaient les AINS (57 %) et la kinésithérapie (54 %). Les traitements spécifiques des douleurs neuropathiques n’étaient utilisés que par une minorité des répondants : 32 % pour les antidépresseurs et 24 % pour les antiépileptiques (24 %). Les traitements non médicamenteux spécifiques des douleurs neuropathiques n’étaient utilisés, eux aussi, que par une très faible proportion des participants : 13 % pour les stimulations électriques transcutanées et 3 % pour la neurostimulation médullaire implantable. Plus de 30 % des patients ont essayé plus de cinq traitements différents et près de la moitié des participants jugeaient leur traitement actuel contraignant. Les principaux intervenants prescripteurs étaient le médecin traitant (40 % des cas), le rhumatologue (20 %) et l’algologue (14,5 %). Ces résultats confirment les difficultés de la prise en charge des douleurs neuropathiques et soulignent la méconnaissance des structures spécialisées.The objective of the Internet EPSIDONE survey was to gain information regarding the management of chronic neuropathic pain in France. To access the questionnaire, the participants had to be more than 18 years old, have a permanent address in France, and suffer from chronic pain (defined as pain for more than 3 months) with neuropathic characteristics identified with the DN4 questionnaire. About 2000 questionnaires were completed between April and August 2008 (78% of the participants were women, aged between 30–60 years). Three quarters of the participants (74%) suffered from intense pain lasting for more than 2 years (60% of the respondents). Pain was mostly located in the back (76%) and/or the lower limbs (70%). The reported causes were mainly: disc hernia (22.7%), vertebral osteoarthritis (16%), surgery (9.3%), nerve injury (9.3%), CRPS (6.7%). About half of the participants (47%) were not aware of the existence of centers specialized in pain management in France and those who knew the existence of such facilities, were not able to localize the pain center closest to their place of residence. In addition to the GPs (68.5% of the respondents), pain was the reason for consulting several other health professionals (more than 5 for 64% of the participants). More than 43% of the participants were not receiving any treatment for their pain. Those who were treated (57%) received mostly NSAIDs and physiotherapy (54%); only 32% received a specific neuropathic pain treatment: antidepressants (32%) or anticonvulsants (24%). Non-pharmacological treatments were used by a minority of participants: 13% were treated with TENS and 3% with chronic spinal stimulation. More than 30% of the participants had received more than 5 treatments and half of the participants judged that their current treatment was inconvenient. The treatments had been prescribed by a GP (40%), a rheumatologist (20%) or a pain specialist (14.5%). These results confirm the major difficulties associated with pain management in France and underscore poor patient awareness about pain centers.

Aims: The aim of the study was to compare sequential versus tailored triple therapy regimens on Helicobacter pylori (H pylori) eradication rates in children and to assess the effect of antimicrobial susceptibility. Patients and Methods: Prospective, open-label, multicenter study. Children received randomly either a 10-day sequential treatment comprising omeprazole (OME) with amoxicillin for 5 days and OME, clarithromycin (CLA), and metronidazole (MET) for the remaining 5 days, or a 7-day triple therapy comprising OME with amoxicillin and CLA in cases of a CLA-susceptible strain or MET in cases of CLA-resistant strain. H pylori eradication was assessed by 13C-urea breath test. Results: One hundred sixty-five children, 95 girls and 70 boys, of median age 10.4 years, were included. The intention-to-treat (ITT) eradication rate was 76.9% (sequential 68/83 = 81.9%, triple therapy 59/82 = 71.9%, ns), and the per-protocol (PP) eradication rate was 84.6% (sequential 68/77 = 88.3%, triple therapy 59/73 = 81.8%, ns). Eradication rates tended to be higher using the sequential treatment, but the difference was only statistically significant for ITT analysis in children harboring both CLA- and MET-susceptible strains (87.8% vs 68.5%, odds ratio [OR] 3.3, P = 0.03). Both ITT and PP eradication rates were significantly lower with sequential treatment in CLA-resistant compared with CLA-susceptible strains (ITT: 56.2% vs 72.7%, OR 5.5, P = 0.008; PP 64.3% vs 80.0%, OR 7.9, P = 0.009). Both treatments were well tolerated. Conclusions: Sequential treatment is greatly effective for eradicating H pylori in children except in CLA-resistant strains. Sequential treatment can be used as a first-line therapy, but only in areas with a low CLA resistance rate.

Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009) and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%-100%). Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7%) in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%).In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily) for at least 12 weeks is highly effective in childhood esophagitis.

There are no solid figures of the frequency of ulcer disease during childhood in Europe. We assessed its frequency and analyzed known risk factors. Patients and methods Ulcers, erosions, indications, and risk factors were recorded in all children undergoing an upper gastrointestinal endoscopy in a prospective study carried out during 1-month simultaneously in 19 centers among 14 European countries. Results Ulcers and/or erosions were observed in 56 out of 694 children. Children with ulcers/erosions were significantly older than those without lesions (10.3±5.5 vs. 8.1±5.7 years, P=0.002). Helicobacter pylori infection was present in 15 of 56 children (27%) where NSAIDs were used in eight, steroids in five, immune-suppressive drugs in five, antibiotics in six, antacids in one, H2-blockers in six and proton pump inhibitors in eight children (more than one risk factor was detected in 32 of 56 children). No risk factors were observed in 24 of 56 children (43%). The main indications for endoscopy were epigastric or abdominal pain (24%) and suspicion of gastroesophageal reflux disease (15%). Similarly, epigastric tenderness, hematemesis, melena, and weight stagnation were significantly associated with ulcers/erosions, whereas sex, H. pylori infection, socioeconomic and lifestyle factors were equally distributed. Conclusion Although limited by the short-time duration and the heterogeneity of the patients included throughout the 19 centers, our study shows a frequency of 8.1% of ulcers and/or erosions in children, occurring mainly in the second decade of life. H. pylori infection and gastrotoxic medications were less frequently implicated than expected.

Peptic ulcer disease has changed profoundly in the last decades in Western countries in both children and adults (1,2). Indeed, the prevalence of Helicobacter pylori–positive ulcers has declined, and a “new” disease has emerged: H pylori–negative gastric or duodenal ulcers (3). In adults, most cases of the latter are due to nonsteroidal anti-inflammatory drugs (NSAIDs) and/or alcohol, and tobacco use can be associated, whereas in children they are not, and their etiology is mostly unknown as are their prevalence and long-term history. This issue of JPGN contains an interesting study about idiopathic peptic ulcer in Chinese children in which the authors report prevalence, symptoms at presentation, and long-term follow-up data (4). The authors enrolled children in whom an ulcer was found during esophago-gastro-duodenoscopy (EGDS), and cases of peptic ulcer secondary to drug use or associated with chronic or acute diseases were excluded. The study, although retrospective, gives important clues about the disease in childhood, the most interesting of which being not only the existence of H pylori–negative ulcers but also their high prevalence. In this series, 6.9% of children undergoing EGDS had an ulcer and in almost half of them (46.5%) no H pylori infection was found. The second most important information we have from this study is the high prevalence of acute gastrointestinal bleeding at presentation. These data are different from other studies, in which only 20% or 27% of childhood peptic ulcers were not associated with either NSAIDs or H pylori(5,6) and in which the most common symptoms at presentation were dyspepsia and/or abdominal pain (7,8). PREVALENCE OF PEPTIC ULCERS IN CHILDHOOD Data on the prevalence of gastric or duodenal ulcers (ie, peptic ulcers) in children are scant. Recently, new information on the prevalence of peptic ulcer in H pylori–infected European children was collected by a register established on the Web site of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition to collect information on the treatment of children with H pylori infection diagnosed during endoscopy by European pediatricians (9). From January 2001 to December 2002, information on 518 children was collected (262 males, median age 9 years, range 1–14 years). At endoscopy, 454 children had gastritis and 64 had an ulcer (12.3%). However, this series included 102 children from Russia and they had a significantly higher prevalence of peptic ulcer (35% vs 6.7% in the remainder of European children, P < 0.0001, odds ratio [OR] 7.5, 95% confidence interval [CI] 4–13). Although bias in the data collected by the register could not be excluded because of the nonrandomized approach to data collection, the prevalence of H pylori–positive ulcers in children differs among countries, and this is not completely explained by the prevalence of the infection in the population studied. The prevalence reported in Chinese children by Tam et al (4) seems higher than in European children. We, therefore, tried to compare it with the prevalence in Italian children (Table 1) by analyzing our database containing data of children undergoing EGDS in the last 20 years. Indeed, the prevalence of peptic ulcer in Chinese children is higher (6.9% vs 3.4% in Italian children, P < 0.0001, OR 2.3, 95% CI 1.5–3.4). Some clinical characteristics were similar in the 2 populations, such as a higher number of males in the group with H pylori–positive ulcers, and their older age as compared with H pylori–negative ulcers, and a lower prevalence of gastric than duodenal ulcer (14% in Chinese and 33% in Italian children). However, there are several important differences between the 2 populations, namely, symptoms at presentation where bleeding is more frequent in Chinese than in Italian children, and the recurrence rate is higher in Chinese children, particularly in H pylori–negative children (Table 1). Moreover, both Italian and Chinese children with H pylori–negative ulcers are younger, and the prevalence of males and females is similar. From these and other data, mainly obtained in adults, it is evident that H pylori–positive and H pylori–negative peptic ulcers are 2 different diseases, and the prevalence of the latter is increasing in both Italian children and adults (10); but the prevalence of H pylori–positive ulcer is not decreasing in children, as it is decreasing in adults. H pylori–positive ulcers in children share some features with those in adults: they occur more frequently in older children and in males, and recurrence rate is low if the infection is eradicated. H pylori–negative ulcers, due to unknown causes, are more frequent in younger children, do not have a gender preference, and tend to have a higher recurrence rate, particularly in Chinese children (4).TABLE 1: Characteristics of gastric and duodenal idiopathic peptic ulcers (PU) in Chinese and Italian childrenLONG-TERM HISTORY In the pre-endoscopic era, recurrence rate was reported to be variable: from 13% found 16 years after radiologically diagnosed peptic ulcer (11), to 70% when the recurrence of symptoms was judged as ulcer relapse (12). When endoscopy became more widely available for use in children, the recurrence rate—endoscopically proven—was 43% in children monitored for 1 year or more (13), and 47% in children monitored until adulthood (14). The natural history of peptic ulcers changed again after the discovery of H pylori, when even in children, eradication of the infection was associated with a cure of the ulcer without long-term recurrence (15). So, the finding of a recurrent ulcer in 1 Chinese child after successful H pylori eradication is surprising, but it is reassuring that all children with recurrent ulcers were asymptomatic and ulcer-free both after a second 4-week course of proton pump inhibitor and at long-term after therapy with proton pump inhibitor, which suggests that all were responders and none had to undergo surgery. In our series of Italian children, no recurrence was seen after successful H pylori eradication and the 2 children with recurrent H pylori–negative ulcers were successfully treated with a second course of ranitidine (unpublished, personal data). So, it seems that even H pylori–negative bleeding ulcers can have a favourable long-term outcome in children. The main question that remains open is the etiology of H pylori–negative and NSAID-negative peptic ulcers in children whose prevalence seems to be increasing. According to Davenport (16), ulcer disease originates from an imbalance between defense mechanisms, such as the mucus gel layer, the confluence between epithelial cells, secretion of bicarbonates, gastric motility and prostaglandins, and aggressive factors such as hydrochloric acid secretion, pepsin, bile, H pylori, and NSAIDs. Thus far, studies on the pathogenesis of gastric and duodenal ulcers have mainly focused on changes in prostaglandins and the mucus gel layer (17), or pepsin production (18) in H pylori–infected children. Similar studies in H pylori–negative children are lacking and are warranted if prevention measures and long-term cure are to be implemented.

AIM:To measure Interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1) in cord blood and assess their relationship with parental allergy and perinatal characteristics. METHODS:In a neonatal care unit 212 consecutive full-term and appropriate for gestational age newborns were recruited. IL-10 and TGF-beta1 levels were determined in cord blood by high sensitivity ELISA. Perinatal characteristics, mode of delivery and presence of allergy in parents were recorded. RESULTS:Out of 212 newborns, 136 were of non-allergic parents and 76 (35.8%) of one or both allergic parents. In newborns of allergic fathers median IL-10 levels tended to be lower (0.67 vs. 1.06 pg/mL, p = 0.07) and TGF-beta1 levels were significantly lower (40.9 vs. 45.3 ng/mL, p = 0.008) than in newborns of non-allergic parents. Multiple general regression analysis showed that presence of paternal allergy (beta=-0.19, p = 0.003) to be born by cesarean section (beta=-0.21, p = 0.03) and younger gestational age (beta= 0.14, p = 0.04) independently contributed to decrease TGF-beta1 levels (multiple R = 0.38, p < 0.0001). CONCLUSION:Paternal allergy and cesarean section are associated to decreased TGF-beta1, which might be the mediator of the increased risk of atopy development. Cord blood IL-10 and TGF-beta1 levels of our newborn series could be used as reference values for further studies on these relationships.