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.

Enhanced gastric IL-18 mRNA expression in Helicobacter pylori-infected children is associated with macrophage infiltration, IL-8, and IL-1 beta mRNA expression.

OBJECTIVE: To investigate IL-18 mRNA expression in the gastric mucosa in Helicobacter pylori-infected children and its association with macrophage infiltration, IL-8, and IL-1 beta mRNA expression. METHODS: From 39 children, blood samples were taken for IL-1 beta gene polymorphism analysis and antral biopsies were obtained for histology (including macrophage immunostaining), culture and semiquantitative analysis of IL-18, IL-8, IL-1 beta, and CD14 mRNA expression by reverse transcription-PCR (RT-PCR). RT-PCR was used for H. pylori ureA and cagA mRNA detection in gastric tissue. RESULTS: H. pylori-infected patients had significantly higher IL-18, IL-8, and IL-1 beta transcript levels and macrophage numbers in the antral mucosa than H. pylori-negative children. IL-1 beta-511/31 gene polymorphism had no impact on gastric IL-1 beta mRNA levels. IL-18 mRNA expression correlated with mRNA expression of IL-8 and IL-1 beta, and transcript levels of all three cytokines were associated with macrophage infiltration and CD14 mRNA expression in the gastric tissue. Significant correlation was also observed between macrophage numbers and histological parameters of gastritis. CONCLUSION: These results suggest that interleukin(IL)-18 and macrophages may have an important function in gastric inflammatory response to H. pylori infection in children. IL-18, and possibly CD14 receptor signalling pathway, may be involved in macrophage activation and subsequent IL-8 and IL-1 beta release.

Results from the pediatric European register for treatment of Helicobacter pylori (PERTH).

BACKGROUND AND AIM: Data on the eradication treatment for childhood Helicobacter pylori are scanty. A register was established on the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) website to collect data on treatment performed by European pediatricians to ascertain what is practiced in the field. SUBJECTS: From January 2001 to December 2002, information on 597 children were entered by 23 European Centers, but only data of 518 treated children were completed and analyzed (86.7%, 262 male subjects, median age 9 years, range 1-14). According to their nationality, 226 children were from Southern Europe, 132 from Eastern Europe, 68 from Western Europe, and 4 from northern Europe, 68 from North Africa, and 20 from Asia. At endoscopy, 454 children had gastritis and 64 had ulcer (12.3%). Antibiotic sensitivity, tested in 361 cases, revealed 18% clarithromycin-resistant and 19% metronidazole-resistant H. pylori strains. RESULTS: Treatment was performed for 1 week in 388 and for 2 weeks in 130 children. Antibiotics were associated with proton pump inhibitors (PPI) in 345 and with bismuth in 121 children. Triple therapy was given to 485 children, dual therapy to 26, quadruple to 7. Follow-up data, by (13)C-Urea-Breath Test or histology or both, were available for 480 children. Overall eradication rate was 65.6%, significantly higher in children with ulcer (79.7%) than without (63.9%, p = .001). When given as first treatment, bismuth-containing triple therapies were more efficacious than PPI-containing ones (77% versus 64%, p = .02, OR 1.88, 95% CI 1.1-3.3). Twenty-seven different treatment regimens were used, but only six were administered to at least 18 children (range 18-157). There was no difference between treatments given for 1 or 2 weeks, or given as first or second therapies. CONCLUSION: European pediatricians entering data in the register used 27 different regimens. Bismuth-containing therapies resulted in higher eradication rate. Omeprazole-containing triple therapies were the most used although their efficacy was low. Therapies recommended for adults do not appear to be suitable for children.

[Efficacy and safety of cyclosporine in the treatment of inflammatory bowel disease in children - a retrospective study]. / Retrospektywna ocena skutczscii bezpieczenstwa leczenia cyklosporyna dzieci z nieswoistym zapaleniem jelit.

AIM: the aim of this study was to report single centre experience with cyclosporine used in treatment of children with inflammatory bowel disease with regard to safety and efficacy. METHODS: retrospective analysis included 23 patients, 21 with ulcerative colitis and 2 with Crohn's disease, aged 2.75 to 18.5 years. They were treated with cyclosporine during the last 5 years. Before cyclosporine therapy was started they received steroids and azathioprine. Cyclosporine treatment was given in severe steroid-resistant exacerbation of the disease (n = 10) or steroid-dependence (n = 13). Cyclosporine dose was set to obtain therapeutic levels (serum concentration > 100 ng/ml and < 200 ng/ml). RESULTS: Cyclosporine treatment was continued up to 2 months in 6 cases, 2 to 6 months in 8 patients and more than 6 months in 9 patients. Complications were reported in 2 patients: hirsutism and gingival hypertrophy. Cyclosporine treatment was stopped in the second case. None of the two patients with Crohn's disease improved during the treatment. Short-term improvement was observed in 11 patients with ulcerative colitis. Long-term recovery (> 6 months) was obtained in 6 cases. In 10 patients with severe exacerbation of ulcerative colitis colectomy was performed, in 4 of them elective surgery was performed when the clinical status improved. CONCLUSION: cyclosporine appears to be a safe and relatively effective treatment of ulcerative colitis in children. Cyclosporine is less effective in maintaining remission and it did not allow to avoid colectomy in severe exacerbation. Still case controlled studies are needed to show the efficacy of this treatment.

Antimicrobial resistance of Helicobacter pylori in Poland: a multicentre study.

The resistance of Helicobacter pylori to antimicrobials, known to be increasing in many countries, is an important factor compromising the efficacy of eradication therapy. Therefore, our study aimed at analysing the current susceptibility status of H. pylori in Poland. A total of 337 H. pylori isolates were cultured from children (N=179) and adults (N=158) from various regions of the country from January 2001 to December 2004. All strains were susceptible to amoxicillin and tetracycline. The overall resistance to clarithromycin (CL) was 28%, but there were significant differences between the centres (ranging from 0% to 33%) and between child and adult isolates (28% versus 15%, respectively; P=0.01) for primary a resistance. Altogether, 46% of H. pylori isolates were resistant to metronidazole (MTZ) and 20% of isolates were simultaneously resistant to CL and MTZ.

Essential fatty acid depletion in children with inflammatory bowel disease.

OBJECTIVE: Children with inflammatory bowel disease (IBD) suffer from malabsorption and malnutrition and therefore may be at risk of developing polyunsaturated fatty acid (PUFA) deficiency. The aim of this study was to investigate PUFA status in children with IBD and the possible relationship to disease activity and nutritional status. MATERIAL AND METHODS: We assessed the fatty acid composition of plasma phospholipids (%wt/wt) of 21 children aged 5.5-18 years with IBD (ulcerative colitis, 15; Crohn's disease, 6) with mild or moderate disease activity. The clinical symptoms and biochemical indices of disease activity and nutritional status (lean and fat body mass, Hb, albumin serum conc.) were also determined. RESULTS: The patients had lower phospholipid PUFAs than 13 healthy, aged-matched controls (25.8+/-5.2 versus 34.2+/-5.7, M+/-SD, p<0.001), mainly due to lower values of linoleic acid (18:2n-6, 14.0+/-3.8 versus 18.3+/-4.3, p<0.01) and its major metabolite arachidonic acid (20:4n-6, 5.3+/-2.0 versus 9.3+/-1.9, p<0.0001). There were also higher values of a-linolenic acid (18:3n-3, 0.3+/-0.4 versus 0.2+/-0.1, p<0.01) while the long-chain n-3 PUFA-eicosapentaenoic and docosahexaenoic acids were normal. Total n-6 PUFA correlated inversely to erythrocyte sedimentation rate (p<0.01), seromucoid (p<0.05) and positively to Hb concentration (p<0.01). CONCLUSIONS: Children with inflammatory bowel disease have a high risk of n-6 PUFA depletion, which is related to disease activity.

Endoscopic ligation of esophageal varices for prophylaxis of first bleeding in children and adolescents with portal hypertension: preliminary results of a prospective study.

BACKGROUND/PURPOSE: Endoscopic variceal ligation (EVL) is effective in controlling rebleeding from esophageal varices in children, but there is no data on the use of EVL to prevent initial bleeding. The objective of this study was to prospectively evaluate the efficacy of EVL in preventing the first hemorrhage from esophageal varices in children. METHODS: Thirty-seven children with portal hypertension (22 liver cirrhosis, 15 portal vein thrombosis), aged 4 to 17 years (M = 9.5 +/- 4.4 years) were included in the study. The criteria for inclusion were (1) no previous variceal bleeding; (2) the presence of esophageal varices classified grade II or more, and (3) their enlargement by at least I grade after 6 months of observation without endoscopic treatment or appearance of endoscopic signs of high bleeding risk. A Multi-Band Ligator was used, and 2 to 6 bands were fixed under general anesthesia during one procedure depending on the number and size of varices. Follow-up examinations were performed every 3 months, repeating the procedure if necessary. In total, 75 procedures of EVL were performed, from one to 5 in each patient RESULTS: Four patients underwent liver transplantation before eradication of varices. Two others were excluded from the observation because of lack of compliance to the protocol. Of the remaining 31 patients, eradication of varices was achieved in 28 children (90.3%) after 2.0 EVL sessions performed at 3-month intervals. The average time of follow-up after cessation of treatment is 16 months. No bleeding from varices occurred in any child during or after treatment. There were no differences in results between children with liver cirrhosis and portal vein thrombosis. Development of hypertensive gastropathy was observed in 2 children with one episode of bleeding. Recurrence of varices without bleeding occurred in 3 children after 12, 13, and 28 months from eradication. CONCLUSIONS: The study results confirmed that endoscopic variceal ligation is a safe and highly effective procedure in children with portal hypertension, regardless of its etiology. Eradication of esophageal varices was followed by 16 months free of bleeding. Prolonged observation is mandatory to conclude if preventive EVL influences the natural history of disease and diminishes the risk of first bleeding onset.

Helicobacter pylori cagA genotype and density of colonization in relation to gastric inflammation in children.

OBJECTIVE: To assess the relationship between density determined by quantitative culture, status, and gastric histology in children. METHODS: Children with clinical symptoms indicating pathology in the upper gastrointestinal tract were referred for endoscopy. From each child blood was taken for serology, and antral biopsies were obtained for quantitative culture of and histology. Histological assessment was performed according to the updated Sydney System. The status of cultured was determined by polymerase chain reaction (PCR) and serum IgG response to CagA by western blotting. RESULTS: Adequate antral biopsies were obtained from 41 children with positive cultures. CagA IgG antibodies were found in 27 patients (66%), 25 of whom were also positive by the PCR. Two children infected with + strains as determined by the PCR were CagA seronegative. Infection with + strains was associated with significantly higher activity of inflammation and denser bacterial colonization in the antrum compared to negative strains. No correlation was observed between the density of colonization and chronic antral inflammation. CONCLUSIONS: This study shows that infection of children with + strains of is associated with enhanced activity of antral inflammation and higher density of colonization. There is a good correlation between serum western blot and bacterial PCR positivity in determining status and a positive relationship between histology and quantitative culture in assessing density in paediatric patients.

Primary resistance of Helicobacter pylori to antimicrobial agents in Polish children.

Helicobacter pylori resistance to antimicrobial agents is an important factor compromising the efficacy of treatment. Therefore the aims of our study were: to determine the prevalence of H. pylori resistance to clarithromycin, metronidazole, amoxycillin and tetracycline in children prior to eradication therapy, to compare different methods of susceptibility testing and to detect mutations responsible for clarithromycin resistance. During 1996-2000, 259 H. pylori strains were isolated from antral gastric biopsies. Susceptibility to antimicrobials was determined by the agar dilution method and the Etest. Mutations in the 23S rRNA gene associated with clarithromycin resistance were analysed by PCR-RFLP and direct sequencing. Overall, ninety-six strains (37%) were resistant to metronidazole, 50 strains (19.3%) were resistant to clarithromycin, and 20 strains (7.7%) were simultaneously resistant to both drugs. All cultured isolates were sensitive to amoxycillin and only one isolate (0.4%) was resistant to tetracycline. The agar dilution method and the Etest showed a perfect category correlation for clarithromycin and 4% discrepancies for metronidazole. Primary resistance to clarithromycin was mainly associated with an A2143G mutation in the 23S rRNA gene of H. pylori. The study highlights the high prevalence of H. pylori primary resistance to clarithromycin in Polish children, which implies a need for pretreatment susceptibility testing.