The natural history of eosinophilic oesophagitis in the transition from childhood to adulthood.

BACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition affecting both children and adults. Little is known about the natural history of EoE in the transition from childhood into adulthood. AIM: To determine the prevalence of EoE symptoms and impact of EoE on quality of life among adults diagnosed with EoE during childhood. METHODS: This is a cross-sectional study of EoE patients from the Children's Hospital of Philadelphia EoE registry. Patients ≥18 years diagnosed with EoE during childhood were administered validated dysphagia [Mayo Dysphagia Questionnaire (MDQ)-30] and Quality of Life (PAGI-QOL) questionnaires. Ongoing EoE treatments were ascertained. RESULTS: A total of 140 EoE patients ≥18 years were identified; 53 completed all questions. Only 6 (11%) subjects had positive (n = 2) or indeterminate (n = 4) dysphagia scores. However, of 47 patients with negative scores, 18 (37%) reported ongoing difficulty swallowing. The mean PAGI-QOL score was 4.58/5. The dietary dimension score was 3.73/5. Current pharmacological EoE treatments were topical steroids (3/53) and interleukin-5 antagonists (3/53). Additionally, 26/53 (49%) were on PPI therapy and 40/53 (76%) were following allergy directed diets. CONCLUSIONS: The majority of young adults diagnosed with EoE during childhood continue to require pharmacological treatment and/or dietary modification for EoE. A substantial proportion of this population experiences ongoing swallowing difficulties that a standard dysphagia questionnaire fails to capture. Dietary quality of life, but not total quality of life, appears to be adversely affected. These data suggest that EoE diagnosed during childhood remains a significant medical issue during early adulthood, and that better EoE symptom measurement instruments are needed.

Success rate and duration of paediatric outpatient colonoscopy.

BACKGROUND: The paediatric colonoscopy completion rates have rarely been reported. AIMS: We sought to evaluate colonoscopy completion rate and compare the rates using colonoscope versus enteroscope. METHODS: We prospectively investigated 60 patients who underwent colonoscopy between July 1999 and June 2001. The following data were collected: demographics, type of endoscope used, extent of colonoscopy, indication for procedure, histology, adverse events and time to reach the caecum and the terminal ileum. RESULTS: Sixty colonoscopies were performed during the study period, 30 with an enteroscope and 30 with a colonoscope. The caecum was reached in 56/60 (93%) and the terminal ileum in 50/60 (83%). An average time of 12.61 min (S.D. 7.3) was necessary to advance the instrument from the anus to the caecum, and additional 3.67 min (S.D. 3.62) to terminal ileum. There was no difference in the success rate between enteroscope and colonoscope. Six patients (10%) had definitive diagnosis established because a full colonoscopy was performed. No serious adverse events occurred. CONCLUSION: Paediatric colonoscopy to the caecum can be completed safely and expeditiously in more than 90% of procedures. Various types of instruments do not appear to influence completion rate. Full colonoscopy contributes to the establishment of a definitive diagnosis.

Famotidine for infant gastro-oesophageal reflux: a multi-centre, randomized, placebo-controlled, withdrawal trial.

BACKGROUND: Gastro-oesophageal reflux afflicts up to 7% of all infants. Histamine-2 receptor antagonists are the most commonly prescribed medications for this disorder, but few controlled studies support this practice. AIM: To evaluate the safety and efficacy of famotidine for infant gastro-oesophageal reflux disease. METHODS: Thirty-five infants, 1.3-10.5 months of age, entered an 8-week, multi-centre, randomized, placebo-controlled, two-phase trial: first 4 weeks, observer-blind comparison of famotidine 0.5 mg/kg and famotidine 1.0 mg/kg; second 4 weeks, double-blind withdrawal comparison (safety and efficacy) of each dose with placebo. RESULTS: No serious adverse events were reported. Eleven patients had 16 non-serious, possibly drug-related adverse experiences: 6 patients with agitation or irritability (manifested as head-rubbing in two), 3 patients with somnolence, 2 patients with anorexia, 2 with headache, 1 patient with vomiting, 1 patient with hiccups, and 1 patient with candidiasis. Of the 35 infants, 27 completed Part I. There were significant score improvements for famotidine 0.5 mg/kg in regurgitation frequency (P = 0.04), and for famotidine 1.0 mg/kg in crying time (P = 0.027) and regurgitation frequency (P = 0.004) and volume (P = 0.01). Eight infants completed Part II on double-blind treatment, which was insufficient for meaningful comparisons. CONCLUSIONS: Histamine-2 receptor antagonists may cause agitation and headache in infants. A possibly efficacious famotidine dose for infants is 0.5 mg/kg (frequency adjusted for age). As 1.0 mg/kg may be more efficacious in some, the dosage may require individualization based on response. Further sizeable placebo-controlled evaluations of histamine-2 receptor antagonists in infants with gastro-oesophageal reflux disease are warranted.

Sedation in pediatric endoscopy.

The increase in diagnostic, radiologic, and minor surgical procedures performed on pediatric patients outside of the traditional surgical suite setting has resulted in a marked increase in the use of conscious sedation. Not long ago, pediatric gastroenterologists were reticent about using intravenous sedation for pediatric endoscopy. With increased experience, careful screening, and the specialization of pediatric gastroenterology, however, endoscopy can now be performed safely with intravenous sedation on almost all patients.

Up-regulation of glutathione S-transferase activity in enterocytes of young children.

The relationship between age and busulfan apparent oral clearance (Cl/F) expressed relative to adjusted ideal body weight and body surface area (bsa) was evaluated in 135 children aged 0 to 16 years undergoing hematopoietic stem cell transplantation for various disorders. Busulfan plasma levels were measured by gas chromatography-mass spectrometry after the first daily dose of the 4-day dosing regimen. Cl/F expressed relative to adjusted ideal body weight (ml/min/kg) and bsa (ml/min/m(2)) was lower in 9- to 16-year-old (y.o.) compared with 0- to 4-y.o. children (49 and 30%; p<.001). We hypothesized that the greater busulfan Cl/F observed in young children was in part due to enhanced (first-pass intestinal) metabolism. Busulfan conjugation rate was compared in incubations with human small intestinal biopsy specimens from healthy young (1- to 3-y.o.) and older (9- to 17-y.o.) children. Villin content in biopsy specimens was determined by Western blot and busulfan conjugation rate was expressed relative to villin content to control for differences in epithelial cell content in pinch biopsies. Intestinal biopsy specimens from young children had a 77% higher busulfan conjugation rate (p =.037) compared with older children. We have previously shown that glutathione-S-transferase (GST) A1-1 is the major isoform involved in busulfan conjugation, and that this enzyme is expressed uniformly along the length of adult small intestine. Thus, the greater busulfan conjugation activity in intestinal biopsies of the young children was most likely due to enhanced GSTA1-1 expression. We conclude that age dependence in busulfan Cl/F appears to result at least in part from enhanced intestinal GSTA1-1 expression in young children.

Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial.

CONTEXT: Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men. The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH. DESIGN: One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994. SETTING: Fourteen pediatric outpatient clinics in the United States and Finland. PATIENTS: Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second periods, respectively. INTERVENTION: Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo. MAIN OUTCOME MEASURES: The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development. RESULTS: Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety parameters. Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation. CONCLUSIONS: This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin. Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required.

Eosinophilic esophagitis: A subset of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis (EG) was first described over 50 years ago. Despite its long history, it remains an ill-defined and poorly understood entity. EG can present in a number of ways, none of which are exclusive to the disorder. EG has features of allergy and immune dysregulation but does not clearly fit into the category of allergic or immune disorder. While EG has been reported to affect all locations and layers of the gastrointestinal tract, the vast majority of reported cases have demonstrated mucosal involvement of the gastric antrum and small intestine in addition to disease activity of other locations of the gastrointestinal tract. Recently, several reports have identified a disease consisting of an isolated esophageal eosinophilia. Eosinophilic esophagitis (EE), also known as primary eosinophilic esophagitis or idiopathic eosinophilic esophagitis, occurs in adults and in children and represents a subset of EG with an isolated severe esophageal eosinophilia. Patients with EE present with symptoms similar to those of gastroesophageal reflux but are unresponsive to antireflux medication. Reports have demonstrated that patients with EE respond to either dietary restriction or corticosteroids.

Placebo-controlled trial assessing the use of oral midazolam as a premedication to conscious sedation for pediatric endoscopy.

BACKGROUND: This study was performed to evaluate the effect of midazolam, as premedication before intravenous conscious sedation, on preprocedural, procedural, and post-procedural patient comfort and anxiety in children undergoing endoscopy. METHODS: A placebo-controlled, double-blind, randomized study was conducted in 123 children (age 7.75 +/- 4.46 years, 56% male) using oral midazolam (0.5 mg/kg, maximum 20 mg) as a premedication before insertion of an intravenous access device (i.v.) and upper endoscopy. Patients were evaluated with regard to changes in vital signs, level of sedation during i.v. placement, level of pre- and post-procedure conscious sedation, ease of separation from parents, ease and duration of procedure, recovery time, and amnesia to objects shown before i.v. placement and immediately before the start of the procedure. RESULTS: A significant difference was noted in the study group for the following parameters: level of sedation for i.v. placement (p < 0.0001), pre-procedural sedation (p < 0.001), ease of i.v. insertion (p < 0.003), ease of separation from parents (p = 0.022), and ease of the nursing personnel's ability to monitor the patient during the procedure (p = 0.0012). The patient's amnesia to an object shown immediately before beginning the endoscopy was increased (p < 0.001). Patients and parents were also more satisfied with the procedure process (p < 0.05). No significant difference was noted with regard to the length or performance of the procedure or recovery time or in the dose of i.v. medication required for successful completion of the endoscopy. CONCLUSION: Oral midazolam is an effective and safe premedication for children undergoing upper endoscopy and should be used in all anxious children and in patients previously judged to be difficult to sedate.

Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids.

BACKGROUND: The histologic appearance of esophageal eosinophils has been correlated with esophagitis and gastroesophageal reflux disease in children. Esophageal eosinophilia that persists despite traditional antireflux therapy may not represent treatment failure, but instead may portray early eosinophilic gastroenteritis or allergic esophagitis. In this study, a series of pediatric patients with severe esophageal eosinophilia who were unresponsive to aggressive antireflux therapy were examined and their clinical and histologic response to oral corticosteroid therapy assessed. METHODS: Of 1809 patients evaluated prospectively over 2.5 years for symptoms of gastroesophageal reflux, 20 had persistent symptoms and esophageal eosinophilia, despite aggressive therapy with omeprazole and cisapride. These patients were treated with 1.5 mg/kg oral methylprednisolone per day, divided into twice-daily doses for 4 weeks. All patients underwent clinical, laboratory, and histologic evaluation before and after treatment. RESULTS: Histologic findings in examination of specimens obtained in pretreatment esophageal biopsies in children with primary eosinophilic esophagitis indicated significantly greater eosinophilia (34.2+/-9.6 eosinophils/high-power field [HPF]) compared with that in children with gastroesophageal reflux disease who responded to medical therapy (2.26+/-1.16 eosinophils/HPF; p < 0.001). After corticosteroid therapy, all but one patient with primary eosinophilic esophagitis had dramatic clinical improvement, supported by histologic examination (1.5 +/-0.9 eosinophils/HPF, p < 0.0001). CONCLUSIONS: Pediatric patients in a series with marked esophageal eosinophilia and chronic symptoms of gastroesophageal reflux disease unresponsive to aggressive medical antire-flux therapy had both clinical and histologic improvement after oral corticosteroid therapy.

Duodenitis in children: correlation of radiologic findings with endoscopic and pathologic findings.

PURPOSE: To determine the accuracy of barium studies in the diagnosis of duodenitis in children. MATERIALS AND METHODS: Seventy-five children (45 boys and 30 girls; mean age, 9 years) underwent upper gastrointestinal (GI) examinations. Twenty-four of the children had biopsy-proved duodenitis, and 51 were healthy control subjects. Radiologic findings were reviewed by two experienced, blinded observers and correlated with endoscopic and histologic results. Duodenal mucosal-fold thickness was measured on spot radiographs (20% magnification), and the extent of disease was evaluated. RESULTS: Of 15 children with mild duodenitis, 13 had normal radiologic findings and 11 had normal findings at esophagogastroduodenoscopy. Of nine children with severe duodenitis, all had friability or ulceration at endoscopy and mucosal-fold thickening of greater than or equal to 4 mm (> or = 3 mm in one infant aged less than 1 year) at upper GI examination. Mucosal-fold thickening was diffuse in patients with celiac, autoimmune, and adenovirus disease and was proximal in patients with peptic ulcer and Crohn disease. Of 51 control subjects, 50 had normal radiologic results, while 47 had normal endoscopic results. The sensitivity of upper GI examination for mild and severe duodenitis combined was 46% with a specificity of 98%, whereas endoscopy had a sensitivity of 54% and specificity of 92%. CONCLUSION: Mucosal-fold thickening was a specific sign of duodenitis in children and should be investigated. Upper GI examination yielded results similar to those at endoscopy.

Pediatric cholesterol screening: missed opportunities.

The current recommendations for childhood cholesterol screening include screening children in whom 1) a parent/grandparent has premature heart or vascular disease or died suddenly; 2) a parent has an abnormal lipid profile; 3) the family history is unobtainable. Over a 3-year period, 256 children referred for hypercholesterolemia were evaluated for heritable hyperlipidemia. We reviewed their family histories and obtained lipoprotein profiles of all of their immediate family members. Of these families, 89 parents had unsuspected hypercholesterolemia of whom 38, whose average age was 36 years, died of a myocardial infarction. In addition, 83 children with no family history of premature coronary artery disease or hypercholesterolemia, were diagnosed with inherited hyperlipidemia (25 with hetrozygous familial hypercholesterolemia, and 58 with familial combined hyperlipidemia). Thus, many adults have no awareness of hyperlipidemia prior to a fatal heart attack, nor of their children as having hyperlipidemia, and a large percentage of children with inherited hyperlipidemia would not have been diagnosed if all of their immediate family members (parents and siblings) had not been screened for a complete lipid profile. These results suggest that in addition to screening, all family members of hypercholesterolemic children, pediatricians and family practitioners should urge parents who may be unaware of their cholesterol levels or have no knowledge of their family history to undergo cholesterol screening in order to comply with NCEP guidelines calling for serum cholesterol measurements in all adults above the age of twenty.

Endoscopic findings in hypertrophic pyloric stenosis: appearance in classic and evolving disease.

BACKGROUND: Hypertrophic pyloric stenosis (HPS) is the most common abdominal surgical disorder in infants. Although the majority of cases are diagnosed by ultrasound, equivocal cases may require endoscopy. This study was performed to assess the various endoscopic appearances of HPS in infants. METHODS: A prospective study comparing the endoscopic appearance of the antrum and pylorus of 18 children with HPS to 21 children in a normal control group. RESULTS: Antral or pyloric mucosal hypertrophy was visualized endoscopically in all 18 study patients. The degree of mucosal thickening varied depending on the age of presentation and duration of symptoms. Antral fold hypertrophy was first noted at 10 days of age, and in the oldest patient (4 months of age) a pyloric mass was noted. By comparison, 21 control infants had no evidence of antral or pyloric narrowing or mucosal thickening. CONCLUSIONS: Upper endoscopy can be a valuable adjunctive diagnostic tool in select cases of HPS when imaging tests are inconclusive or when infants present with clinical symptoms outside the typical age-time frame for HPS. Because HPS may evolve over time, it is important that the endoscopist recognize the different appearances of HPS.

Gastric fluid volume in infants for pyloromyotomy.

PURPOSE: To quantify gastric fluid volumes in infants with pyloric stenosis presenting for pyloromyotomy and to demonstrate endoscopically the efficacy of blind aspiration for gastric fluid recovery. We hypothesized that previous diagnostic contrast studies, preoperative nasogastric suction, and fasting interval would not affect these volumes. METHODS: Seventy-five infants scheduled for pyloromyotomy were given atropine before induction of anaesthesia. For those who had undergone preoperative nasogastric suction, the nasogastric tube was aspirated and removed. A 14 F multiorificed orogastric catheter was blindly passed to aspirate gastric fluid for measurement. Following tracheal intubation, 15/75 subjects underwent gastroscopy to measure residual gastric fluid. RESULTS: Gastric fluid volume removed by blind aspiration averaged 4.8 +/- 4.3 ml.kg-1 with 83% of patients having > 1.25 ml.kg-1. Although 14 of the 15 patients evaluated by endoscope had < or = 1 ml residual gastric fluid, one had 1.8 ml.kg-1. Recovery of total gastric fluid volume by blind aspiration averaged 96 +/- 7%. The large gastric fluid volumes were independent of a history of barium study, preoperative nasogastric suction, and fasting interval. CONCLUSION: Infants with pyloric stenosis have large gastric fluid volumes which are not substantially reduced by preoperative nasogastric suction. Blind aspiration of gastric contents prior to induction of anaesthesia provides a reliable estimate of total gastric fluid for most of these infants, although the occasional infant may retain a small amount of gastric fluid. The clinical importance of such a residual volume is uncertain.

Gastric fluid measurement by blind aspiration in paediatric patients: a gastroscopic evaluation.

PURPOSE: Numerous investigators have estimated gastric fluid volume using blind aspiration through multi-orificed catheters, but none have confirmed the validity of this technique in infants and children. We sought to validate the accuracy of this technique in a fasted paediatric population by using gastroscopy. Data from several studies were then combined to generate a gastric fluid volume frequency distribution for healthy paediatric patients fasted for surgery. METHODS: This is a prospective study of 17 patients aged six months to 11 yr who underwent elective upper endoscopy at a paediatric teaching hospital. Gastric contents were aspirated blindly with a syringe and a 16 or 18F multi-orificed orogastric tube, and the volume of gastric contents removed in the supine and decubitus positions was measured. Residual gastric fluid was aspirated using an endoscope. Data from 611 infants and children enrolled in previously published studies utilizing the same blind aspiration technique were pooled and a gastric fluid volume frequency distribution was created. RESULTS: Blind aspiration removed 97 +/- 8% of the total gastric fluid volume. In 661 children presenting for elective surgery, the gastric fluid volume was 0.40 +/- 0.45 ml.kg-1. Median volume was 0.27 ml.kg-1, with the 95%ile at 1.25 ml.kg-1 and an upper limit of 4.1 ml.kg-1. CONCLUSION: Blind aspiration of gastric contents accurately estimates gastric fluid volume for paediatric patients fasted for surgery. Population estimates for gastric fluid volume in otherwise healthy fasted paediatric patients are shown.

Failed Nissen fundoplication in two patients who had persistent vomiting and eosinophilic esophagitis.

The following report describes two patients who had chronic symptoms of gastroesophageal reflux and persistent histological esophagitis, despite aggressive medical antireflux therapy, who continued to have esophagitis and remained symptomatic post antireflux surgery (Nissen fundoplication). Both patients demonstrated a severe eosinophilic esophagitis with normal gastric and duodenal histology before and after surgery. Postoperatively, each received the diagnosis of allergic enteritis and both responded clinically and histologically to oral corticosteroids and an elemental diet.

Breakdown of gastric staple line as a complication of the uncut Collis-Nissen fundoplication in children.

Uncut Collis-Nissen fundoplication for complicated gastroesophageal reflux was performed in 102 children (46 girls; age 5.6 +/- 4.2 years). Five patients developed intractable emesis postoperatively (average 11 +/- 5 months after surgery) and were found to have two independent luminal openings at the gastroesophageal junction seen on upper endoscopy but not demonstrable on upper GI. The defect was presumed to occur from breakdown of the original staple line on the lesser gastric curve. The condition was successfully repaired in all patients by including a new staple line and rewrapping of the stomach. Practitioners should be aware of this previously unreported complication post uncut Collis-Nissen fundoplication and that this condition may not be excluded by a normal upper GI study.

Pediatric enteral access center: a multidisciplinary approach.

The need for enteral access and gastrostomy placement in children has increased dramatically over the past several years. In the following article, we present a case report of a typical patient undergoing evaluation for enteral nutrition and enteral access. Following the case report, we describe our newly formed Pediatric Enteral Access Program including patient selection, the method of gastrostomy placement, risks and benefits, cost analysis, and follow-up of this ever-increasing population of children.