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.

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.

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.

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.

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.

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.

Surgery results in significant improvement in growth in children with Crohn's disease refractory to medical therapy.

Inflammatory bowel disease (IBD) in children can cause significant impairment in linear growth, and delay in pubertal onset. The aim of this study was to assess the impact of surgery on linear growth in children with Crohn's disease (CD) who were resistant to medical therapy, and had documented evidence of growth impairment. We performed a retrospective study on eight consecutive patients with refractory disease who had attended the paediatric IBD clinic. All patients underwent surgery as part of their treatment. Height and weight were recorded at least 6 months prior to surgery, at the time of surgery, and 6 months post surgery. Growth velocities and height Z-scores were calculated. All patients had evidence of sustained growth suppression prior to surgery. Three patients had evidence of growth failure. There was a significant increase in height velocity from 0.15 cm/month before surgery to 0.54 cm/month after surgery (P = 0.006). There was also a significant decrease in the modified Harvey-Bradshaw index (HBI) of disease activity from 2.00 before surgery, to 0.84 after surgery (P = 0.003). Improvements in height Z-score and weight velocity after surgery were not significant on statistical analysis. Our study demonstrates that before surgery, children with CD refractory to therapy have sustained growth suppression, and in some cases may even have growth failure. Surgical intervention before puberty appears to result in a significant improvement in height velocity and disease activity. These findings need to be further investigated with carefully designed prospective studies.

Treatment of Helicobacter pylori gastritis improves dyspeptic symptoms in children.

BACKGROUND: In adults, the treatment of Helicobacter pylori infection is only recommended for patients with active gastric or duodenal ulcers. It is not known whether similar guidelines can be applied to children because the prevalence of peptic ulcer disease in childhood is estimated to be much lower than in adults. The purpose of this study was to determine whether treatment of H. pylori gastritis would improve symptoms of dyspepsia in children. METHODS: Sixteen patients (5 boys, 11 girls) aged 14 +/- 1.2 years who had symptoms of dyspepsia were evaluated using upper gastrointestinal endoscopy with biopsies to establish the diagnosis of H. pylori gastritis. They were treated for 2 weeks with clarithromycin, amoxicillin, and a proton pump inhibitor. Dyspepsia symptoms were evaluated by a questionnaire before and after treatment of the infection. The effect of H. pylori treatment on the total symptom score was analyzed with use of the Student t test. Values are presented as mean +/- SEM. RESULTS: All patients had antral nodularity and chronic active gastritis with spiral-shaped organisms but no evidence of peptic ulcer disease. Mean total symptom score decreased significantly at 2 to 4 weeks after treatment (12.6 +/- 0.9 vs. 2.1 +/- 0.5 P < 0.001), and it remained low (2.9 +/- 0.7) at follow-up 9.7 +/- 1.4 months (range, 2-24 months later). CONCLUSION: These results suggest that the treatment of H. pylori gastritis can improve dyspeptic symptoms in children.

Gastrointestinal stromal tumour of the duodenum in a 7-year-old boy.

We report a 7-year-old boy presenting with an acute upper gastrointestinal (GI) haemorrhage subsequently diagnosed to have a very rare duodenal gastrointestinal stromal tumour (GIST). Endoscopy, pertechnetate and red cell scans were negative. Abdominal US detected a 17-mm mass lesion of the third part of the duodenum. This was confirmed on CT and shown to be hypervascular on selective angiography. At laparotomy, a 20-mm submucosal duodenal lesion was found associated with mucosal ulceration. Immunohistochemical analysis revealed it to be positive for CD117 (c-KIT protein) consistent with a GIST. We emphasize the importance of a thorough abdominal US examination in children with GI haemorrhage and the consideration of GIST in the diagnosis after the common causes have been excluded.

The seroprevalence of Helicobacter pylori in a referral population of children in the United States.

OBJECTIVES: The purpose of this study was to determine the prevalence of serum antibodies directed against Helicobacter pylori (H. pylori) in children referred to children's hospitals or medical centers throughout the United States. METHODS: This multisite cross-sectional prospective study involved 992 children from 12 states using a validated anti-H. pylori IgG enzyme immunoassay. The children were recruited into two groups: those without any GI complaints (non-GI referral, n = 619) and those who were referred for endoscopy because of abdominal pain (GI referral, n = 373). RESULTS: GI referral children had a higher rate of seropositivity (22.5%) than non-GI referral children (14.1%) from the same geographic regions. In both groups, older children were more likely to be seropositive for H. pylori, as were nonwhite children and those with lower socioeconomic status. H. pylori seropositivity rates were higher in GI referral children with four or more household members (relative risk [RR] = 1.47; CI 1.01-2.14). Multivariate analysis controlling for age, ethnicity, and household income, showed that presence of GI symptoms were associated with a nearly 2-fold risk for H. pylori seropositivity (odds ratio = 1.77, CI 1.27-2.47). Epigastric pain (RR = 2.21; CI = 1.33-3.66) and having three or more episodes of abdominal pain in the last 3 months (RR = 0.59, CI = 0.35-0.99) were the only specific symptoms significantly associated with H. pylori seropositivity. CONCLUSIONS: The H. pylori seropositivity rate of GI referral children with symptoms of abdominal pain was significantly higher. H. pylori infection in early childhood was found to be associated primarily with the child's household size and socioeconomic status.