Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS: A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS: A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION: Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.

Systematic Review and Meta-analysis of Histological Gastric Biopsy Aspects According to the Updated Sydney System in Children.

OBJECTIVES: A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori-positive versus H pylori-negative children referred for upper gastrointestinal endoscopy. METHODS: The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale, and a meta-regression analysis was done. The study was registered on the PROSPERO platform. RESULTS: Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5990 H pylori-infected and 17,782 uninfected children.H pylori-positive versus H pylori-negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta-regression analysis showed that H pylori-positive versus H pylori-negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pylori prevalence. CONCLUSIONS: H pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.

Helicobacter pylori Infection in Pediatric Patients Living in Europe: Results of the EuroPedHP Registry 2013 to 2016.

OBJECTIVES: The aim of the study was to assess clinical presentation, endoscopic findings, antibiotic susceptibility and treatment success of Helicobacter pylori (H. pylori) infected pediatric patients. METHODS: Between 2013 and 2016, 23 pediatric hospitals from 17 countries prospectively submitted data on consecutive H. pylori-infected (culture positive) patients to the EuroPedHP-Registry. RESULTS: Of 1333 patients recruited (55.1% girls, median age 12.6 years), 1168 (87.6%) were therapy naïve (group A) and 165 (12.4%) had failed treatment (group B). Patients resided in North/Western (29.6%), Southern (34.1%) and Eastern Europe (23.0%), or Israel/Turkey (13.4%). Main indications for endoscopy were abdominal pain or dyspepsia (81.2%, 1078/1328). Antral nodularity was reported in 77.8% (1031/1326) of patients, gastric or duodenal ulcers and erosions in 5.1% and 12.8%, respectively. Primary resistance to clarithromycin (CLA) and metronidazole (MET) occurred in 25% and 21%, respectively, and increased after failed therapy. Bacterial strains were fully susceptible in 60.5% of group A, but in only 27.4% of group B. Primary CLA resistance was higher in Southern and Eastern Europe (adjusted odds ratio [ORadj] = 3.44, 95% confidence interval [CI] 2.22-5.32, P < 0.001 and 2.62, 95% CI: 1.63-4.22, P < 0.001, respectively) compared with Northern/Western Europe. Children born outside Europe showed higher primary MET resistance (ORadj = 3.81, 95% CI: 2.25-6.45, P < 0.001). Treatment success in group A reached only 79.8% (568/712) with 7 to 14 days triple therapy tailored to antibiotic susceptibility. CONCLUSIONS: Peptic ulcers are rare in dyspeptic H. pylori-infected children. Primary resistance to CLA and MET is markedly dependent on geographical regions of birth and residence. The ongoing survey will show whether implementation of the updated ESPGHAN/NASPGHAN guidelines will improve the eradication success.

Sub-10-minute High-quality Diagnostic Colonoscopy With Terminal Ileum Intubation in Children Is Feasible and Safe.

OBJECTIVES: To critically appraise ileocolonoscopy (IC) practice in a large tertiary center, where IC is exclusively performed by experienced pediatric colonoscopists, particularly focusing on indications for the procedure; bowel preparation efficacy; IC completion rates and timings; diagnostic yield; and complications. PATIENTS AND METHODS: We prospectively evaluated all patients referred to our clinic between July 2015 and June 2016. Data on age, height and weight, sex, surgical history, indications for colonoscopy, bowel preparation given, and bowel cleansing efficacy were collected. The following were calculated: percentage of terminal ileal (TI) intubation; time to terminal ileum; total duration of each procedure. In addition, we evaluated the number and the type of complications encountered and the number of patients readmitted within 30 days from the elective procedure. Endoscopic diagnostic yield, stratified for indication, was calculated. RESULTS: A total of 1392 patients were referred; 181 required an endoscopic evaluation of the lower gastrointestinal (GI) tract (Outpatient Department conversion rate: 13%). Main indications for IC were: recurrent abdominal pain 38.1%; unexplained chronic diarrhea 16%; suspected inflammatory bowel disease (IBD) 24.9%; isolated rectal bleeding 13.2%; occult GI bleeding 1.6%; unexplained faltering growth 1.6%; IBD restaging 2.6%; and miscellaneous 1.6%. Terminal ileum was reached in all the patients (TI intubation rate = 100%). Median time to TI was 9.8 minutes (1-50 minutes). Time to TI was lower in younger patients compared to older ones (P = 0.005). Bowel cleansing was judged as grade 1 in 49.2%; grade 2 in 33.7%; grade 3 in 13.3%; and grade 4 in 3.9%. A significant statistical correlation was recorded between bowel cleansing and time to TI. The positive diagnostic yield was: 11.6% in patients with abdominal pain; 37.9% in patients with chronic diarrhea; 51.1% in patients with suspected IBD; 29.2% in patients with isolated rectal bleeding; 33.3% in patients with occult GI bleeding; 0% in patients with faltering growth; and 33% in the miscellaneous group. CONCLUSIONS: In conclusion, appropriately targeted IC in the management of children with GI symptoms is a safe, fast, and useful investigation. TI intubation rates of 100% are achievable and desirable and can be conducted quickly. Poor bowel preparation impacts negatively on this and IC duration may be faster in younger children. High diagnostic yields have been recorded in patients with a clinical suspicion of IBD. Diagnostic yield in isolated recurrent abdominal pain is low. Training to excellence in pediatric IC should be a persistent goal.

Pediatric Eosinophilic Esophagitis: Results of the European Retrospective Pediatric Eosinophilic Esophagitis Registry (RetroPEER).

OBJECTIVES: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. METHODS: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. RESULTS: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ±â€Š33.5 months and age at diagnosis was 8.9 ±â€Š4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. CONCLUSIONS: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.

Endoscopy in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto IBD Group of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Endoscopy is a central tool for the evaluation and management of inflammatory bowel disease (IBD). In the last few decades, gastrointestinal (GI) endoscopy has undergone significant technological developments including availability of pediatric-size equipment, enabling comprehensive investigation of the GI tract in children. Simultaneously, professional organization of GI experts have developed guidelines and training programs in pediatric GI endoscopy. This prompted the Porto Group on Pediatric IBD of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition to develop updated guidelines on the role of GI endoscopy in pediatric IBD, specifically taking into considerations of recent advances in the diagnosis, disease stratification, and novel therapeutic targets in these patients.

Use of Infliximab Biosimilar Versus Originator in a Pediatric United Kingdom Inflammatory Bowel Disease Induction Cohort.

OBJECTIVES: The aim of the study was to summarize short-term effectiveness, safety, and cost of using infliximab biosimilar (IFX-B) drugs, (Inflectra [Hospira] and Remsima [NAAP]) compared to originator infliximab (IFX-O) (Remicade [MSD]) in biologic naive pediatric inflammatory bowel disease in the United Kingdom. METHODS: Prospective audit of patients starting anti-tumour necrosis factor (TNF) therapy. Disease severity, response to treatment, and remission rate was measured by Pediatric Crohn's Disease Activity Index (PCDAI) and/or Physician Global Assessment. RESULTS: Between March 2015 and February 2016, 278 patients (175 IFX-O, 82 IFX-B, and 21 Adalimumab) were started on anti-TNF therapy. This was compared with collected data on 398 patients started on IFX-O from 2011 to 2015. At initiation, median PCDAI was 36 (20,48) (n = 42) in the IFX-O group and 28 (20,40) (n = 29) in the IFX-B group, (P = 0.08). Immunosuppression rates were similar: 150/175 (86%) for IFX-O and 65/82 (79%) for IFX-B (P > 0.05). Post induction, median PCDAI score was 5 (0,11) (n = 19) and 0 (0,8) (n = 15) in the IFX-O and IFX-B groups, respectively (P = 0.35). There was no difference in response to treatment using Physician Global Assessment 85% (n = 28) in IFX-O group and 86% (n = 19) in IFX-B group (P > 0.05). Adverse events at initiation and post induction were not different between both groups (P > 0.05). Using conservative calculations, £875,000 would have been saved for a 1-year period with universal adoption of biosimilars in patients who were instead treated with IFX-O. CONCLUSIONS: IFX-B is likely as effective as IFX-O in treating IBD in comparable pediatric populations. Sites should adopt infliximab biosimilar for new starts due to cost reduction with no difference in other parameters.

Improved Medical Treatment and Surgical Surveillance of Children and Adolescents with Ulcerative Colitis in the United Kingdom.

Background: Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC. Methods: A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits. Results: Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%). Conclusions: A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042_video1izy042.video15769503407001.

Real-life Anti-tumor Necrosis Factor Experience in More Than 500 Patients: High Co-immunosuppression Rates But Low Rates of Quantifying Treatment Response.

OBJECTIVE: The aim of this study was to measure the effectiveness, safety, and use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel disease in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment +/or the Paediatric Crohn Disease Activity Index. RESULTS: A total of 37 centers participated (23/25 specialist pediatric inflammatory bowel disease sites). A total of 524 patients were included: 429 with Crohn disease (CD), 76 with ulcerative colitis (UC), and 19 with IBD unclassified (IBDU). Eighty-seven percent (488/562) of anti-TNF was infliximab; commonest indication was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95); 79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median time from diagnosis to treatment was 1.42 years (interquartile range 0.63-2.97). Disease (at initiation) was moderate or severe in 91% (156/171) by Physician Global Assessment compared to 41% (88/217) by Paediatric Crohn Disease Activity Index (Kappa (κ) 0.28 = only "fair agreement"; P < 0.001.Where documented, 77% (53/69) of patients with CD responded to induction; and 65% (46/71) entered remission. A total of 2287 infusions and 301.96 years of patient' follow-up (n = 385) are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98) adalimumab infusions (no deaths or malignancies). Peri-anal abscess drainage was less common after anti-TNF initiation (CD), that is 26% (27/102) before, 7% (3/42) after (P = 0.01); however, pre and post anti-TNF data collection was not over equal time periods. CONCLUSIONS: Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools, which need to be addressed to improve ongoing patient care.

Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.

BACKGROUND & AIMS: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. METHODS: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. RESULTS: Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00). CONCLUSIONS: Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.

Seronegative Coeliac Disease in Children: A Case Report and Review of the Literature.

Serology is frequently used for the diagnosis of coeliac disease in children; however, a small proportion of children are seronegative. We present a case of seronegative coeliac disease along with literature review to include diagnostic and management dilemmas.

Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN.

The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.

Pediatric IBD-unclassified Is Less Common than Previously Reported; Results of an 8-Year Audit of the EUROKIDS Registry.

BACKGROUND: Inflammatory bowel disease-unclassified (IBD-U) is diagnosed in ∼10% of pediatric and adolescent onset IBD patients. The EUROKIDS registry (2004) initiated by the Porto IBD working group of ESPGHAN prospectively monitors diagnostic workup of newly diagnosed pediatric and adolescent onset IBD patients. We aimed to describe diagnostic workup, phenotype, and change of diagnosis over time in pediatric IBD-U patients. METHODS: Data were collected on children from 52 centers across 20 European countries and Israel, diagnosed with IBD from May 2005 through November 2013. Full endoscopy plus small bowel radiology was considered complete diagnostic workup. Participating centers reporting IBD-U patients were queried in 2014 for follow-up data. RESULTS: IBD-U was the provisional first diagnosis in 265 of 3461 children (7.7%) (91/158 [58%] with pancolitis; 140 [53%] male), diagnosed more frequently under the age of 10 (median age 12.3 years, 89 [34%] under 10 years). Half (48%) had undergone complete diagnostic workup. Lack of small bowel radiology was the prevailing reason for incomplete workup. As a result of reinvestigations (endoscopy in 54%, radiology in 38%) during a median follow-up of 5.7 years (interquartile range, 2.5-7.8), a change in diagnosis from IBD-U to Crohn's disease (12%) or ulcerative colitis (20%) was reported. CONCLUSIONS: Only half of patients reported as IBD-U in EUROKIDS had undergone complete diagnostic workup. Follow-up with reinvestigations resulted in a reduction of IBD-U rate to 5.6%. A diagnosis of IBD-U becomes less likely in case of complete diagnostic workup. Implementation of clear diagnostic criteria will further reduce the rate of IBD-U in the future.

Potential for improving therapy and defining new research targets in eosinophilic oesophagitis based on understanding of immunopathogenesis.

OBJECTIVES: This review considers the potential for therapeutic advances in the management of eosinophilic oesophagitis (EoE) based on recently increased understanding of the pathophysiology of the disorder. METHODS: This is a review of publications characterising mucosal changes and leucocyte recruitment patterns in human and experimental EoE. RESULTS: EoE, although diagnosed by epithelial infiltration of eosinophils, is actually a transmural inflammation in which eosinophil recruitment occurs via the deeper layers. Penetration of eosinophils into the epithelium is variable, explaining the need for multiple biopsies to diagnose what may be a clearly visible disorder. Fibrosis and neuromuscular dysfunction both occur within the subepithelial tissues. Recent murine studies have identified that T-cell recruitment underpins antigen-specific oesophageal eosinophil recruitment. Involvement of innate immunity is also suggested by the role of invariant natural killer T cells in experimental EoE. CONCLUSIONS: Looking beyond present therapeutic options with a view to future studies, we identify T cells as candidates for "upstream therapy" if antigen specificity or homing markers are determined. Evidence of aeroallergen sensitisation suggests the possibility of lymphocyte priming within nasal-associated lymphoid tissue or Waldeyer ring, with the potential for topical therapy. We consider acquired neuromuscular dysfunction as a therapeutic target in acute symptomatic deterioration or bolus obstruction. We assess possible similarities with therapeutic stratagems for chronic asthma, recognising at the same time the anatomic specificity of the oesophagus and the difficulty in delivering effective topical medication to subepithelial tissues in this location compared with the airway.

Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children.

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.

Hepatic expression of cell proliferation markers and growth factors in giant cell hepatitis: implications for the pathogenetic mechanisms involved.

OBJECTIVES: The aim of this study is to determine whether amitotic division or nuclear proliferation is involved in the formation of giant cells (GCs) in giant cell hepatitis (GCH). PATIENTS AND METHODS: Liver sections from 18 pediatric patients with idiopathic infantile GCH and 12 patients with postinfantile GCH were evaluated for the expression of proliferating cell nuclear antigen (PCNA) and human histone 3 (H3) mRNA, transforming growth factor-alpha (TGF-α), TGF-ß1, hepatocyte growth factor (HGF), and epidermal growth factor receptor (EGFR). RESULTS: Proliferation markers were detected in 1% to 80% in the nuclei of GC and non-GC hepatocytes in 10 of 18 (56%) infantile GCH biopsies and 11 of 12 (92%) postinfantile GCH biopsies, but not in normal liver. The expression of proliferation markers in GCs paralleled that in non-GC hepatocytes (P < 0.05 for both markers). TGF-α and EGFR were detected in both GCs (9/29 and 4/30 patients with infantile or postinfantile GCH, respectively) and non-GC hepatocytes (15/29 and 11/30 patients with infantile or postinfantile GCH, respectively). TGF-ß1 and HGF were detected mainly in sinusoidal cells in 20 of 29 and 10 of 30 patients with infantile or postinfantile GCH, respectively; the expression of HGF was positively correlated with PCNA and H3 mRNA in non-GC hepatocytes and with H3 mRNA in GCs (P < 0.01). CONCLUSIONS: Hepatic expressions of nuclear proliferation markers and growth factors were similar in infantile and postinfantile GCH, nuclear proliferation markers were detected in both GCs and non-GC hepatocytes in a high proportion of patients, and expression of HGF correlated positively with the proliferation markers. These data indicate that nuclear proliferation may contribute to the pathogenesis of GCs in at least a proportion of patients with GCH. A model for the pathogenesis of GCH is proposed.

Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study.

UNLABELLED: 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.

Percutaneous liver biopsy in hemophiliac children with chronic hepatitis C virus infection.

OBJECTIVE: To develop a protocol for safe performance of percutaneous liver biopsies in children with deficiency of factor VIII (n = 12) or IX (n = 2) and chronic hepatitis C virus infection. PATIENTS AND METHODS: Liver biopsies were performed after administration of factor VIII or IX, before and 24 weeks after cessation of antiviral therapy. To define the optimal means of providing replacement therapy, 10 children were enrolled in a randomized crossover design study of bolus versus continuous factor VIII for performance of the liver biopsy. For the crossover study, all of the patients were given a loading dose of 50 +/- 5 IU recombinant factor (rF)VIII/kg; a minimum of factor VIII activity of > or = 80% 30 to 60 minutes following factor VIII infusion was required for liver biopsy. For the bolus protocol, rFVIII 25 to 50 IU/kg was given 6, 14, 24, 36, 48, and 60 hours after completion of the loading dose. For the continuous protocol, rFVIII was given 3 to 4 IU/kg per hour for 48 hours, followed by a bolus of 25 IU/kg at 60 hours. In patients with factor IX deficiency, a loading dose of 100 IU/kg was followed by a bolus of 50 IU/kg at 3, 15, 27, and 48 hours after the loading dose. RESULTS: Twenty liver biopsies were performed in children with factor VIII deficiency without major complications. One of the 3 biopsies in the patients with factor IX deficiency was complicated by a hemoperitoneum. Midazolam and fentanyl were used in the first 8 patients. However, postbiopsy pain, presumably secondary to hematoma in 2 patients and hemoperitoneum in 1, prompted us to use ultrasound to locate a suitable biopsy site and to change to propofol; this allowed us to better immobilize the liver, to minimize postbiopsy bleeding. The subsequent 15 biopsies were well tolerated without postbiopsy pain or other complication. CONCLUSIONS: Percutaneous liver biopsy in children with factor VIII deficiency can be safely performed using either bolus or continuous infusion of recombinant factor VIII. A brief general anesthetic and ultrasound guidance are recommended.

Constipation in childhood: a multidisciplinary approach to management in the community.

Three per cent of children in the community may be affected by chronic constipation. Causes of constipation may be organic or functional: the cornerstone of management is thorough interview and physical examination to identify appropriate investigations, identify causes and decide on management. Whatever the cause, faecal impaction must be managed as the first phase of treatment using appropriate medications. Other strategies may include increasing the fibre content of the child's meals and increasing fluid intake. Getting into a regular toilet habit helps prevent constipation and a structured toileting programme promotes the resumption of faecal continence.