Long-term maintenance treatment with omeprazole in children with healed erosive oesophagitis: a prospective study.

BACKGROUND: Short-term studies show that PPIs heal erosive esophagitis in children. There are no prospective studies that examine long-term maintenance therapy of erosive esophagitis in children with and without underlying GERD-predisposing disorders. AIM: To determine prospectively the dose of omeprazole needed to maintain remission of erosive oesophagitis and reflux symptoms in children. METHODS: Patients aged 1-16 years with healed erosive reflux oesophagitis after omeprazole treatment (0.7-3.5 mg/kg/day) entered a 21-month maintenance phase where they initially received half the dose of omeprazole required to heal. Endoscopy was performed after 3, 12 and 21 months. The omeprazole dose was increased if erosive oesophagitis or reflux symptoms recurred. RESULTS: A total of 46 patients entered the study and 32 completed it. Of these, 17 (53%) remained on the maintenance dose, 12 (38%) returned to their healing dose and 3 (9%) ended the study on a dose higher than their healing dose. Three-quarters of the completers (24/32) had no erosive oesophagitis relapse. Four patients (13%) had relapse of only erosive oesophagitis, 4 (13%) had relapse of erosive oesophagitis and symptoms, and 10 (31%) had only symptomatic relapse. Of the 46 patients, 48% had GERD-predisposing disorders (neurological impairment or oesophageal atresia). Overall, 62.5% (5/8) of patients who had an erosive oesophagitis relapse had a GERD-predisposing disorder versus 33.3% (8/24) of those who did not. CONCLUSIONS: Remission of erosive oesophagitis is maintained with omeprazole treatment for at least 21 months in most children aged 1-16 years, and the drug is well tolerated. To maintain remission, some 60% of patients require more than half the dose required for healing. In children with GERD-predisposing conditions, GERD is often chronic and relapsing, and requires long-term management.

Gastric histology in children treated with proton pump inhibitors long term, with emphasis on enterochromaffin cell-like hyperplasia.

BACKGROUND: There are longstanding concerns that carcinoid tumours or atrophic gastritis might develop in children receiving proton pump inhibitors (PPIs) long term. In children, this has not been studied using stains sensitive and specific for enterochromaffin-like (ECL) cells. AIM: To evaluate gastric biopsies for ECL hyperplasia or gastric atrophy, in children treated long-term with PPIs. METHODS: Synaptophysin and chromogranin immunostaining, biopsies read anonymised, blinded. Endocrine cell numbers graded according to Rindi and Solcia. RESULTS: Of 130 children with gastro-oesophageal reflux disease (GERD), 65 had sequential gastric biopsies, starting at median 8.2 years (<1 to 17). Of the 65, 83% had GERD-predisposing conditions, mostly neurological impairment or repaired oesophageal atresia. Four hundred and fifty-eight tissue blocks (208 antrum, 250 body) were available from a mean of 5.8 endoscopies (2-14). Of 82 gastric body biopsies in 40 patients with ECL hyperplasia, 67 had grade 1 hyperplasia, 15 grade 2. Of the 40, nine had ECL hyperplasia before PPI use; all nine had received H2-receptor antagonists. Median duration of PPI use was 3.17 years in patients with ECL hyperplasia, 2.20 years in those without (P=0.16). Helicobacter pylori was present in four patients; two had ECL hyperplasia. PPI duration was >3 years in 24 patients. In nine patients who received H2-receptor antagonists, changes were present before PPI use. No patient had atrophic gastritis. CONCLUSIONS: A high percentage of children (61%) receiving long-term PPI continuously for up to 10.8 years (median 2.84 years) develop minor degrees of ECL hyperplasia. This has no known clinical significance. Children on PPIs for this duration do not appear to develop atrophic gastritis or carcinoid tumours.

Outcomes of fundoplication: causes for concern, newer options.

Antireflux surgery has been a mainstay of treatment for gastro-oesophageal reflux disease in children for some 40 years. In recent years, enthusiasm for antireflux surgery seems only to have increased, despite its often poor outcome, and the availability of highly effective medical therapy in the form of proton pump inhibitors (PPIs). Reports show that many children undergo surgery without reflux disease as the demonstrable cause of their symptoms/signs, and without evidence of having failed optimised medical management. Very few studies report objective testing postoperatively--those that do show high rates of failure within the first 1-3 years following surgery. Treatment with PPIs is an effective and safe alternative to surgery in many cases.

Pyloric balloon dilation for delayed gastric emptying in children.

Delayed gastric emptying may manifest with symptoms of epigastric pain, early satiety and delayed vomiting, and at times may be associated with failure to thrive. These symptoms and signs may improve following surgical pyloroplasty. To determine whether pyloric balloon dilation (PBD) is an effective therapy for children with these symptoms, hospital records of all children who underwent endoscopic PBD between October 1991 and March 1994 at British Columbia's Children's Hospital were reviewed. Excluded were children with chromosomal abnormalities, neurological disorders and erosive esophagitis. Through-the-scope balloons of diameter 15 or 18 mm were positioned in the pyloric channel and inflated with air to 2334 or 1815 mmHg respectively, for 2 min. Nineteen children with a mean age of 3.75 years (range eight months to 10 years) who presented with symptoms for more than three months (mean 11 months) were identified. Eleven children presented with failure to thrive, 14 with delayed vomiting and 10 with early satiety. Results of gastric emptying tests at 90 min ranged from 8% to 75% (mean 32%). The pylorus was difficult to intubate in 11 of 19 children, and in two the pylorus could not be passed before PBD. No complications were experienced with PBD. Thirteen children had complete resolution of symptoms, and five had transient improvement lasting four to eight weeks after PBD with subsequent complete resolution of symptoms following surgical pyloroplasty. One child continued to have mild symptoms after PBD but did not have further treatment. This study suggests that PBD is a safe and effective therapeutic option in children with symptoms and signs associated with delayed gastric emptying.

Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group.

OBJECTIVES: To determine the efficacy, safety, and tolerability of omeprazole in children and to determine the doses required to heal chronic, severe esophagitis. STUDY DESIGN: Open multicenter study in children aged 1 to 16 years with erosive reflux esophagitis. The healing dose of omeprazole used was that with which the duration of acid reflux was <6% of a 24-hour intraesophageal pH study. Follow-up endoscopy was performed after 3 months of treatment with the healing dose. RESULTS: At entry, two thirds of 57 patients who completed the study had esophagitis grade 3 or 4 (scale 0-4); some 50% had neurologic impairment or repaired esophageal atresia. Of the 57 patients, 54 healed; 3 did not heal and left the study, and 3 healed with a second course. Doses required for healing were 0.7 to 3.5 mg/kg/d: 0.7 mg/kg/d in 44% of patients and 1.4 mg/kg/d in another 28%. Healing dose correlated with grade of esophagitis but not with age or underlying disease. Reflux symptoms improved dramatically in almost all of the 57 patients, including the unhealed patients. CONCLUSIONS: Omeprazole is well tolerated, highly effective, and safe for treatment of erosive esophagitis and symptoms of gastroesophageal reflux in children, including children in whom antireflux surgery or other medical therapy has failed. On a per-kilogram basis, the doses of omeprazole required to heal erosive esophagitis are much greater than those required for adults.

Pharmacokinetics of orally administered omeprazole in children. International Pediatric Omeprazole Pharmacokinetic Group.

OBJECTIVES: The aim of this study was to examine the pharmacokinetics of orally administered omeprazole in children. METHODS: Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, and tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pathological acid reflux on 24 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normalized. Children remained on this dose for 3 months, and during this period the pharmacokinetics were measured. RESULTS: A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional for subjects and was performed in 25 of the 57 enrolled. The doses of omeprazole required were substantially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the ranges previously reported in adults. However, the plasma levels, area under the plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (Cmax), were lower in the younger age group, when the AUC and Cmax were normalized to a dose of 1 mg/kg. Furthermore, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups. CONCLUSIONS: The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a per kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children.

Indicaciones pediátricas actuales de la cisaprida: toma de posesión de la European Society for Pediatric Gastroenterology, Hepathology and Nutrition / Current pediatric indications for cisapride: a position paper by a panel convened by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition

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Pediatric gastrointestinal mucosal biopsy. Special considerations in children.

In most disorders of the gastrointestinal mucosa that occur in children and adults, the mucosal manifestations are the same. This article focuses on disorders and approaches to gastrointestinal procedures and mucosal biopsy that are of a particularly or peculiarly pediatric nature. This article discusses, in detail, the issues pertaining to endoscopy and other techniques of mucosal biopsy in children. Some approaches and techniques are considerably different than those in adults.

Peptic ulcer disease in children.

A peptic ulcer in a child looks the same as it does in an adult, and many of the aetiologies of peptic ulcer disease in children are similar to those in adults. However, there are many differences between children and adults, especially in the areas of clinical presentation, the prevalences of different types of ulcer disease, and the prevalence of complications of ulcer disease. Therefore the approach to diagnosis and management in children is often at variance with that in adults. One important example is the approach to suspected Helicobacter pylori (H. pylori) disease in children, in which consensus groups have advised a considerably different approach in children. While the chapter deals with the full range of peptic ulcer disease in children, the focus is on those aspects in which there are differences between adults and children.

Canadian Helicobacter Study Group Consensus Conference on the Approach to Helicobacter pylori Infection in Children and Adolescents.

Gastric infection with Helicobacter pylori is common in both children and adults, but children are considerably less susceptible to peptic ulcers and other pathological sequelae. As a result, the risk to benefit ratio of diagnostic studies and therapeutic regimens for H pylori in adults are likely different from those in pediatric populations. These guidelines for the management of pediatric H pylori infection, developed by the Canadian Helicobacter Study Group, are designed to identify when the diagnosis and treatment of H pylori may improve patient care. Given the low prevalence of this infection in Canada, it is important to recognize that indiscriminate testing and treatment programs in children are not recommended, and indeed may threaten the optimal care of children. Diagnostic tests should be employed judiciously and be reserved for children who are most likely to derive measurable benefit, such as those likely to have peptic ulcer disease. At this time a test and treat strategy in children cannot be considered prudent, evidence based or cost effective. It is appropriate to limit diagnosis and treatment to children and adolescents in whom H pylori has been identified during endoscopic investigation.

The role of cisapride in the treatment of pediatric gastroesophageal reflux. The European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND: Cisapride is a gastrointestinal prokinetic agent that is used worldwide in the treatment of gastrointestinal motility-related disorders in premature infants, full-term infants, and children. Efficacy data suggest that it is the most effective commercially available prokinetic drug. METHODS: Because of recent concerns about safety, a critical and in-depth analysis of all reported adverse events was performed and resulted in the conclusions and recommendations that follow. RESULTS: Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisapride is given to pediatric patients who can be considered healthy except for their gastrointestinal motility disorder, and the maximum dose does not exceed 0.8 mg/kg per day in 3 to 4 administrations of 0.2 mg/kg (not exceeding 40 mg/d), no special safety procedures regarding potential cardiac adverse events are recommended. However, if cisapride is prescribed for patients who are known to be or are suspected of being at increased risk for drug-associated increases in QTc interval, certain precautions are advisable. Such patients include those:(1) with a previous history of cardiac dysrhythmias, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or disease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc interval should be used before initiation of therapy and after 3 days of treatment to ascertain whether a cisapride-induced cardiac adverse effect is present. CONCLUSIONS: With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced doses. If higher doses than this are given, the precautions above are advisable. In any patient in whom a prolonged QTc interval is found, the dose of cisapride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and the administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be restarted at half dose with control of the QTc interval. Unfortunately, at present, normal ranges of QTc interval in children are unknown. However, a critical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater than 470 milliseconds as outside it.

Spectrum of gastritis in celiac disease in childhood.

Celiac disease (CD) may cause changes throughout the gastrointestinal tract. The pathology is best described in the distal duodenum and jejunum. It is also associated with lymphocytic gastritis (LG) and varioliform gastritis in adults and children, but the histologic spectrum in the gastric biopsy and the clinical implications are undefined. In this report we relate our experience with the clinical, endoscopic, and histologic changes in gastric biopsies in CD in childhood. Slides (hematoxylin and eosin stained) were reviewed from 33 celiac children, 5 having had more than 1 gastric biopsy during a 7-year period. Gastric intraepithelial lymphocyte (IEL) counts were compared with those of 10 histologically normal controls (normal range, 1-7 IEL/100 antral or body epithelial cells) and 10 nonceliac chronic gastritis (CG) biopsies without H. pylori (normal range, 1-19 IEL/100 antral cells), noting changes in the epithelium and lamina propria (LP). LG was present in 29/33 initial biopsy sets. Fifteen of 29 showed LG/CG. The IEL number was greater in LG/CG than in LG only (27.2 +/- 9.3, n = 14 vs. 18.6 +/- 13.4, n = 15 in the antrum; 23.5 +/- 2.8, n = 4 vs. 13.0 +/- 8.4 in the body). In CD the difference between these mean values and those of normal and nonceliac CG controls was statistically significant. In CG/LG the inflammatory infiltrate was predominantly diffuse/superficial in the LP; mucin depletion was noted in 11/15. The IELs were in the LG/CG range in two CG controls. The IELs were normal at follow-up in five cases. There were no statistically significant differences between the groups with respect to clinical parameters or gastric endoscopic findings. No child had varioliform gastritis. We conclude that in CD children, the stomach is endoscopically unremarkable but may show LG, or LG/CG with or without mucin depletion, or occasionally appear normal. Gastric histology returned to normal with gluten withdrawal. Normal gastric histology is not typical, but does not exclude CD.