Exploring potential noninvasive biomarkers in eosinophilic esophagitis in children.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EE) continues to present clinical challenges, including a need for noninvasive tools to manage the disease. To identify a marker able to assess disease status in lieu of repeated endoscopies, we examined 3 noninvasive biomarkers, serum interleukin (IL)-5, serum eosinophil-derived neurotoxin (EDN), and stool EDN, and examined possible correlations of these with disease phenotype and activity (symptoms and histology) in a longitudinal study of children with EE. SUBJECTS AND METHODS: Children with EE were studied for up to 24 weeks (12 weeks on 1 of 2 corticosteroid therapies and 12 weeks off therapy). Twenty children with normal esophagogastroduodenoscopies with biopsies were enrolled as controls. Serum IL-5, serum EDN, and stool EDN were measured at weeks 0, 4, 12, 18, and 24 in children with EE, and at baseline alone for controls. Primary and secondary statistical analyses (excluding and including outlier values of the biomarkers, respectively) were performed. RESULTS: Sixty subjects with EE (46 [75%] boys, mean age 7.5 ±â€Š4.4 years) and 20 normal controls (10 [50%] boys, mean age 6.7 ±â€Š4.1 years) were included. Significant changes in serum EDN (significant decrease from baseline to week 4, and then rebound from week 4 to week 12) occurred. Serum EDN levels were stable after week 12. Serum IL-5 and stool EDN levels in subjects with EE were not statistically different from those of the control subjects when each time point for the cases was compared with the controls' 1-time measurement. CONCLUSIONS: Serum EDN levels were significantly higher in subjects with EE than in controls, and the results suggest a possible role, after additional future studies, for serum EDN in establishing EE diagnosis, assessing response to therapy, and/or monitoring for relapse or quiescence.

Feeding after percutaneous endoscopic gastrostomy in children: early feeding trial.

BACKGROUND: Percutaneous endoscopic placement of a gastrostomy tube is a common procedure to provide feeding access in children. The practice has been to withhold the initial feeding for a prescribed length of time because of safety concerns. The shortest reported time to feeding in pediatric patients is 6 hours. PATIENTS AND METHODS: A prospective randomized trial was devised to compare the tolerance of feedings at 3 and 6 hours after percutaneous endoscopic gastrostomy placement. The change in abdominal girth before and 1 hour after the initial feeding, any vomiting, and the gastric residual volume before the next feeding were recorded. The length of stay was also documented. RESULTS: Forty successive patients who met the entry criteria were enrolled, with 20 in each group. There were no statistical differences between the groups for age or sex distribution. There were no significant differences in the recorded episodes of emesis from either group (median value 0 in both groups, P = 0.82). The changes in abdominal girths were also similar and statistically not significantly different (median values 0 for 3 hours vs 0.5 cm for 6 hours, P = 0.29). Gastric residual volumes were low overall and not different depending on the time that feedings were started (median value 0 in both groups, P = 0.47). The length of stay was statistically the same between the 3- and 6-hour feeding groups (median values 30.7 hours for 3 hours vs 30.0 hours for 6 hours, P = 0.92). CONCLUSIONS: Feedings after percutaneous endoscopic gastrostomy placement can be started as soon as 3 hours after the procedure is completed with no increase in complications.

Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children.

BACKGROUND & AIMS: Although eosinophilic esophagitis is recognized increasingly, outcome data guiding therapy are limited. We conducted a prospective randomized trial comparing oral prednisone (P) and swallowed fluticasone (F) for histologic and clinical response. METHODS: Patients were randomized to receive P or F for 4 weeks, followed by an 8-week weaning protocol. Esophageal histology was evaluated at baseline and after 4 weeks of therapy. Clinical assessments were performed at weeks 0, 4, 12, 18, and 24. RESULTS: Eighty patients with eosinophilic esophagitis were enrolled: 40 in the P arm and 40 in the F arm. Histologic improvement was seen in 30 of 32 P and 34 of 36 F patients, with a greater degree of histologic improvement in the P group. All P and 35 of 36 F patients were free of presenting symptom(s) at week 4. Symptom relapse was seen in 45% of patients by week 24. Kaplan-Meier analysis showed no difference between P and F with regard to relapse rate (P = .7399). No significant difference in time to relapse was found between groups (P = .2529). Systemic adverse effects were noted in 40% of the P arm, whereas esophageal candidal overgrowth was seen in 15% of the F arm. CONCLUSIONS: Systemic and topical corticosteroids were effective in achieving initial histologic and clinical improvement. P resulted in a greater degree of histologic improvement, without evidence of an associated clinical advantage over F in terms of symptom resolution, relapse rates, or time to relapse. Symptom relapse was common to both groups upon therapy discontinuation, highlighting the need for maintenance treatment protocols.

Carbohydrate and lipid metabolism following infliximab therapy in pediatric Crohn's disease.

Improvements in insulin resistance after anti-TNF-alpha therapy have been reported in inflammatory conditions, although no changes were noted in adult patients with Crohn's disease. There is no information concerning insulin resistance and substrate metabolism in children with Crohn's disease after anti-TNF-alpha therapy. Our aim was to describe changes in carbohydrate and lipid metabolism in children with active Crohn's disease after their initial dose of infliximab. Children with active Crohn's disease underwent measurement of plasma insulin and glucose just before and 2 wk after their initial infusion of infliximab, an anti-TNF-alpha antibody. In addition, resting energy expenditure, with determination of both carbohydrate and lipid oxidation rates, was determined. Measurements were conducted in both fasting and parenterally fed states. Despite no changes in resting energy expenditure, a significant reduction (p < 0.05) in RQ (5%) and carbohydrate oxidation rate (24%), with a corresponding increase in lipid oxidation rate (42%) was found during parenteral nutrition infusion. No differences in plasma insulin, glucose, and insulin resistance were noted when comparing pre- and postinfliximab measurements.

Effects of infliximab and parenteral nutrition on albumin and fibrinogen synthesis rates in pediatric Crohn disease.

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) may play a significant role in growth disturbance in pediatric Crohn disease. The aim of this study was to determine the effects of anti-TNF-alpha therapy on albumin and fibrinogen synthesis during both fasting and parenteral nutrition infusion in pediatric patients with active Crohn disease. PATIENTS AND METHODS: Children with active Crohn disease scheduled for their initial dose of infliximab underwent assessment immediately before and 2 weeks following infliximab infusion. Using the stable isotope [d5] phenylalanine, rates of fractional and absolute albumin and fibrinogen synthesis were calculated. Measurements were made in both the fasting and parenterally fed states. RESULTS: Fifteen children (mean age 14.9 +/- 0.3) completed the study. The mean serum albumin changed from 3.59 +/- 0.08 to 3.66 +/- 0.04 g/dL, and the mean fibrinogen level decreased from 230 +/- 17 to 187 +/- 8 mg/dL (P < 0.05) following infliximab therapy. During fasting, there were no changes in albumin and fibrinogen synthesis rates following infliximab. During parenteral nutrition infusion, the fractional albumin synthesis rate changed from 11.8% to 15.1%/day (P = 0.06), and the absolute albumin synthesis rate increased from 192 to 248 mg x kg(-1) x day(-1) (P < 0.05), whereas no changes in fibrinogen synthesis rates were observed. Synthesis rates of albumin and fibrinogen were increased during parenteral nutrition infusion compared with the fasting state. CONCLUSIONS: Following infliximab therapy, during parenteral nutrition infusion, albumin synthesis increased significantly. Conversely, serum fibrinogen levels decreased following infliximab therapy in the absence of significant change in synthesis rates.

Protein and energy metabolism response to the initial dose of infliximab in children with Crohn's disease.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) may contribute to the alterations in protein and energy metabolism present in children with Crohn's disease (CD), who frequently suffer from growth disturbance. We hypothesized that anti-TNF-alpha therapy would reduce protein losses, due to decreased proteolysis and increased protein synthesis, and that anti-TNF-alpha therapy would decrease resting energy expenditure. METHODS: Children with active CD underwent metabolic assessment immediately before and 2 weeks following initial infliximab infusion. Using the stable isotopes [d5] phenylalanine and [1-13C] leucine, 2 independent measures of protein metabolism were determined during fasting and in response to parenteral nutrition. Energy expenditure, determined by indirect calorimetry, was measured in fasting and parenterally fed states. RESULTS: Fifteen children completed the study. Following infliximab therapy, significant reductions in proteolysis (P < 0.05) were noted in the fasting state (8%-11%) and during parenteral nutrition infusion (10%-12%). Phenylalanine utilization for protein synthesis decreased significantly (8%-13%) following infliximab (P < 0.05). Protein balance was not significantly altered. No significant changes in energy expenditure were observed following infliximab in fasting or parenterally fed states. Supplementation with parenteral nutrition resulted in significantly decreased proteolysis (8%-21%; P < 0.05), increased protein synthesis (37%-45%; P < 0.01), and improved protein balance (P < 0.01) compared to the fasting state. CONCLUSIONS: Following the initial infliximab infusion in children with CD, proteolysis and protein synthesis were significantly reduced in the fasting and parenterally fed states. Supplementation with parenteral nutrition resulted in significant improvements in protein metabolism compared to the fasting state both before and after infliximab therapy.

Accuracy and tolerability of the Bravo catheter-free pH capsule in patients between the ages of 4 and 18 years.

OBJECTIVE: The aim of this study was to determine if the Bravo pH capsule is comparable to the nasally placed pH catheter in terms of pH-metry, safety, and tolerability in children. METHODS: Ten patients each in the age ranges of 4 to 6 years, 7 to 10 years, and >10 years were tested simultaneously with the catheter and the capsule. Six each were tested with the catheter alone or the capsule alone. Subjects recorded adverse events and graded tolerance (in terms of activity, appetite, and satisfaction) on a scale of 1 to 5, with a score of 5 indicating that the device was well tolerated. A 24-hour reflux index and 24- and 48-hour reflux indices were generated from the catheter and capsule, respectively. Student t test, Mann-Whitney U test, and Fisher exact test were used to compare reflux index, tolerability, and adverse events between the catheter and capsule. RESULTS: Sixty-six patients 4 to 16 years of age (mean, 9.4 years) were enrolled. There was no statistically significant difference between the mean reflux indices (RIs) obtained simultaneously with the catheter and capsule in all patients combined on day 1 (P = 0.0665). There was a significant difference between day 2 and days 1 and 2 combined with the capsule versus the catheter (P = 0.007 and P = 0.0107); however, a discordant result of normal RI on day 1 and pathological RI on day 2 was seen in only 1 patient. The capsule was better tolerated than the catheter in terms of appetite (P = 0.029), activity (P = 0.001), and satisfaction (P = 0.003). There were no significant complications. CONCLUSIONS: The Bravo pH capsule was as accurate and safe and better tolerated than the conventional pH catheter in children 4 years of age and older.

At what age is a suction rectal biopsy less likely to provide adequate tissue for identification of ganglion cells?

OBJECTIVE: The objective of this study was to determine at what age suction rectal biopsy is less likely to provide adequate tissue to detect submucosal ganglion cells in a child being evaluated for Hirschsprung disease. PATIENTS AND METHODS: Children > or =1 year of age undergoing a rectal biopsy at a single children's hospital had 1 biopsy each obtained simultaneously with a suction biopsy device and a grasp biopsy forceps. The biopsies were examined by 2 pathologists for adequacy of the submucosa (none, scant, adequate, or ample) and the presence of ganglion cells. The 2 specimens were compared with each other. RESULTS: One hundred fifty-two children 1 to 17 years of age were included. Fifty-three were female. Subjects were grouped into 4 age categories: 1 to 3 years (group A), 4 to 6 years (group B), 7 to 9 years (group C), and > or =10 years (group D). Similar numbers of patients were recruited for each group. Ganglion cells were identified in 73% and 90% by the suction and grasp devices, respectively, in group A. In groups B through D, ganglion cells were identified in 50% to 53% vs 92% to 97% of the suction and grasp biopsies, respectively (P < 0.001). Submucosa was present in 88% (suction) vs 98% (grasp) in group A, 70% vs 95% in group B, 69% vs 94% in group C, and 45% vs 92% in group D. CONCLUSION: The suction rectal biopsy is less likely to provide adequate submucosa for identification of ganglion cells after 3 years of age.

Patient-reported symptoms after pediatric outpatient colonoscopy or flexible sigmoidoscopy under general anesthesia.

OBJECTIVES: Endoscopic examination of the colon is indicated in children with diarrhea, hematochezia and suspected inflammatory bowel disease. The aim of this study was to determine the rate of patient-reported symptoms after colonoscopy and flexible sigmoidoscopy under general anesthesia in children. PATIENTS AND METHODS: This prospective study included patients 18 years of age and younger who underwent colonoscopy or flexible sigmoidoscopy during a 1-year period. At least 30 days after the endoscopy, an interview was conducted regarding symptoms after colonoscopy or flexible sigmoidoscopy. RESULTS: Eighty-eight children were eligible, and 68 (77%) were available for follow-up. Ten (15%) reported symptoms after their endoscopy. The most common symptoms reported were diarrhea, excessive gas and sore throat. The frequency of reported symptoms was similar between colonoscopy and flexible sigmoidoscopy. The frequency of symptoms was not affected by intubation of terminal ileum, polypectomy or the number of prior colonoscopies or flexible sigmoidoscopies. CONCLUSIONS: Outpatient colonoscopy and flexible sigmoidoscopy under general anesthesia are well tolerated by children. A minority of children reports mild symptoms that spontaneously resolve.

Severity of basal cell hyperplasia differs in reflux versus eosinophilic esophagitis.

OBJECTIVES: Basal cell hyperplasia of the esophageal epithelium is a frequent finding in children with histological evidence of esophagitis. The aim of this study was to compare the severity of basal cell hyperplasia in gastroesophageal reflux vs eosinophilic esophagitis. METHODS: A cohort of pediatric patients who underwent same-day endoscopy with esophageal biopsy and 24-hour esophageal pH monitoring was divided into groups based on endoscopic and pH monitoring findings. Basal cell hyperplasia was defined as normal (< or = 25% of esophageal epithelial height), mild (26%-50%), moderate (51%-75%) or severe (> 75%). The severity of basal cell hyperplasia in patients with abnormal pH monitoring studies, both with and without endoscopic abnormalities of the esophagus, was compared with the severity in patients with eosinophilic esophagitis. RESULTS: Twenty-seven children with abnormal pH monitoring were identified. Of these 27 children, 11 had endoscopic findings consistent with reflux esophagitis. Thirty patients with eosinophilic esophagitis were identified. Patients with eosinophilic esophagitis had significantly increased severity (P < 0.001) of basal cell hyperplasia (87% severe, 3% moderate, 3% mild, 7%, normal) than patients with abnormal esophageal pH monitoring alone (11% severe, 4% moderate, 15% mild, 70% normal) or in combination with endoscopic abnormalities (18% severe, 9% moderate, 18% mild, 55% normal). CONCLUSIONS: Basal cell hyperplasia is more severe in children with eosinophilic esophagitis than in those with reflux esophagitis. The finding of basal cell hyperplasia is a powerful clue into the underlying etiology of pediatric esophagitis and, along with epithelial eosinophil count, can be used as information to guide therapy.

Gastrointestinal factors in autistic disorder: a critical review.

Interest in the gastrointestinal (GI) factors of autistic disorder (autism) has developed from descriptions of symptoms such as constipation and diarrhea in autistic children and advanced towards more detailed studies of GI histopathology and treatment modalities. This review attempts to critically and comprehensively analyze the literature as it applies to all aspects of GI factors in autism, including discussion of symptoms, pathology, nutrition, and treatment. While much literature is available on this topic, a dearth of rigorous study was found to validate GI factors specific to children with autism.

Assessment of the effectiveness of biofeedback in children with dyssynergic defecation and recalcitrant constipation/encopresis: does home biofeedback improve long-term outcomes.

The purpose of this study was to determine whether biofeedback benefits children with dyssynergic defecation and constipation/encopresis, and whether home biofeedback improves long-term outcomes. Thirty-six patients with chronic constipation who had failed at least 6 months of conventional treatment and demonstrated dyssynergic defecation at anorectal manometry were randomized to biofeedback in the laboratory alone (group 1, n=24) or in the laboratory and at home (group 2, n=12) and followed up at 2, 4, and a mean of 44 months. Thirty patients were available for long-term follow-up. Bowel movements increased in all from a mean of 1.4/week to 5.1, 5.8, and 5.1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Soiling decreased in all from a mean of 5.5/week to 0.6, 0.1, and 1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Laxative use decreased from a mean of 4.1 days/week to 0.6, 0.3, and 0.7 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Twenty-seven of 30 parents ranked their satisfaction a mean of 2.2 (range 1-excellent to 3-good). There were no significant differences in outcomes between the laboratory alone group and the laboratory plus home group. Biofeedback is beneficial for some children with chronic constipation and dyssynergic defecation. Supplemental home biofeedback does not improve long-term outcomes.

Comparison of serological markers of inflammatory bowel disease with clinical diagnosis in children.

BACKGROUND: Our purpose was to study the concordance of serological tests for inflammatory bowel disease with clinical diagnosis established by traditional testing in children. METHODS: All children seen in our division who had IBD Diagnostic System (ie, pANCA, ASCA IgA, and ASCA IgG) performed over a 21-month period (June 1998 to February 2000) were identified. Their medical records were reviewed for basic demographics, test results (endoscopy, histology, and radiology), IBD Diagnostic System results, and patient symptoms/medications. Results of the IBD Diagnostic System were compared with several patient characteristics including age, sex, absence/presence of symptoms, medication use, disease activity and duration. RESULTS: One hundred seven patients were divided into 6 groups based on clinical diagnosis and IBD Diagnostic System results. The sensitivity, specificity and +/- predictive values of the IBD Diagnostic System for ulcerative colitis were 69.2, 95.1, 90.0, and 87.1%, respectively, and for Crohn's disease were 54.1, 96.8, 90.9, and 80.8%, respectively. Overall, the results of the IBD Diagnostic System were concordant with the clinical diagnosis in 76 of the 107 (71%) patients. CONCLUSIONS: In our experience, the specificity of IBD Diagnostic System is better than the sensitivity; the sensitivity is better for ulcerative colitis than Crohn's disease (69.2% vs 54.1%). The low sensitivity, especially for Crohn's disease, precludes the possibility that the IBD Diagnostic System can replace traditional studies when evaluating for inflammatory bowel disease. Though we do not exclude inflammatory bowel disease solely by IBD Diagnostic System results, it is reassuring to note that all patients without clinical evidence of inflammatory bowel disease also had negative IBD Diagnostic System results.

Is there a seasonal variation in the incidence or intensity of allergic eosinophilic esophagitis in newly diagnosed children?

INTRODUCTION: Allergic eosinophilic esophagitis (AEE) is thought to be an allergic reaction that is characterized by inflammation caused by predominant accumulation of eosinophils in esophageal mucosa (> or =15 eosinophils per high power field). AIMS: To examine the seasonal distribution of newly diagnosed AEE children. METHODS: Retrospective analysis of all patients diagnosed with AEE at our institution over a nearly 6-year period (December 1998 to October 2004). RESULTS: Two hundred thirty-four children (mean age 7.3 y, median age 7.0 y, age range 0.2 to 19.5 y) were diagnosed with AEE during the study period. Significantly fewer patients were diagnosed with AEE in Winter as compared with Spring, Summer, and Fall. Although all the patients had severe eosinophilic esophagitis, the intensity of esophageal eosinophilia was less in Winter than in Summer or Fall, but not Spring, seasons. CONCLUSIONS: A seasonal variation was noted with Winter, a season of low outdoor allergens, having the fewest number of newly diagnosed AEE patients.

Cytokine expression in normal and inflamed esophageal mucosa: a study into the pathogenesis of allergic eosinophilic esophagitis.

OBJECTIVES: We studied the expression of cytokines and inflammatory cells in normal and inflamed esophageal mucosa of children with the aim of furthering our understanding of the pathophysiology of allergic eosinophilic esophagitis (AEE). METHODS: Controls and AEE patients (>or=15 eosinophils/high-power field on esophageal mucosal biopsies) between the ages of 1 and 18 years were recruited. Esophageal biopsies were obtained for histologic examination, immunohistochemical studies, and cytokine analysis. RESULTS: Eight controls (4 males; mean age 9.99 years) and 11 AEE patients (8 males; mean age 7.15 years) were studied. mRNA expression of interferon (IFN)-gamma, interleukin (IL)-4, IL-5, IL-13, eotaxin-1, eotaxin-2, eotaxin-3, and RANTES was studied. IFN-gamma and IL-5 expressions were significantly up-regulated in AEE patients compared with controls. Expressions of IL-4 and IL-13 were similar between AEE patients and controls. Eotaxin-1 expression was significantly up-regulated in AEE patients, whereas eotaxin-2 was up-regulated in controls. Expression of RANTES and eotaxin-3 was similar between the two groups. There was increased staining for mast cells in AEE patients compared with controls. CONCLUSIONS: Our data suggests that AEE is primarily an IL-5 selective TH2 response, with a possible TH1 component, and a differential role of eosinophilic chemoattractants. The role of mast cells in the pathogenesis of AEE needs additional study.

Clinical presentation of patients with eosinophilic inflammation of the esophagus.

BACKGROUND: Allergic eosinophilic esophagitis (AEE) is defined by a dense infiltrate of eosinophils within the esophageal mucosa and the absence of pathological gastroesophageal reflux. OBJECTIVE: To characterize a pediatric population with AEE to determine if AEE can be diagnosed based on history; to compare patients with varying degrees of esophageal eosinophilic inflammation to determine if moderate esophageal inflammation is part of a continuum of AEE. DESIGN: Medical records of 112 patients with eosinophils on esophageal biopsy specimens were reviewed. Patients were grouped according to eosinophils per high power field (eos/hpf): group 1 (1-5 eos/hpf, n = 31), group 2 (6-14 eos/hpf, n = 13), and group 3 (> or =15 eos/hpf, n = 68) and compared. SETTING: University Children's Hospital. PATIENTS: Children and adolescents with eosinophils on esophageal mucosal biopsy specimens. INTERVENTIONS: Analysis of clinical information. MAIN OUTCOME MEASUREMENTS: Clinical characterization of patients with esophageal eosinophilia. RESULTS: There was no significant difference in patient demographics. Patients in groups 2 and 3 had multiple food allergens identified. Patients in group 3 with a positive type I allergic response were significantly younger than those with a negative response (mean, 4.6 years old vs mean, 8.5 years old; P = .0065). In group 2, 3 of 13 patients responded histologically to acid-suppressive therapy, whereas 6 patients had improved histology with corticosteroids; 4 of these 6 patients had not responded histologically to acid-suppression. LIMITATIONS: Retrospective study. CONCLUSIONS: History and clinical presentation were not useful in predicting the severity of histologic esophageal inflammation in this cohort. Patients with moderate esophageal eosinophilia (group 2) exhibited a variable response to medical therapy.

Cysteinyl leukotriene levels in esophageal mucosal biopsies of children with eosinophilic inflammation: are they all the same?

OBJECTIVES: Allergic eosinophilic esophagitis (AEE) is characterized by intense eosinophilic inflammation of the esophageal mucosa. Cysteinyl leukotrienes (CysLT) are eosinophil chemoattractants. We studied CysLT levels in esophageal mucosa of children with AEE and controls. METHODS: CysLT levels (pg CysLT/microg protein) were quantified by Enzyme-linked Immunosorbent Assay (ELISA) on endoscopically obtained esophageal mucosal biopsies. RESULTS: Twelve children with AEE (eight boys, mean age 6.6 yr, range 1.0-14.5 yr) and 10 controls (six boys, mean age 9.56 yr, range 1.08-15.08 yr) were enrolled. None were on anti-LT or corticosteroid therapy. All controls had histologically normal mucosal biopsies of the esophagus, stomach, and duodenum. Patients with AEE had intense eosinophilic inflammation of the esophageal mucosa (mean 39 eosinophils/hpf, range 15-70 eosinophils/hpf) and a normal 24-h pH probe study. CysLT levels were similar between the two groups: mean levels were 12.44 (median 10.87, range 2.54-28.29) in AEE patients and 9.52 (median 9.26, range 1.71-21.64) in controls. CysLT levels did not correlate with the degree of esophageal eosinophilic inflammation. Incidentally, five patients with eosinophilic gastroduodenitis, in addition to esophagitis, were enrolled; their CysLT levels were statistically higher than those of controls. CONCLUSIONS: This is the first study to examine CysLT levels in esophageal mucosal biopsies of children with AEE and normal children. CysLT levels in AEE patients are similar to those in controls, and independent of the severity of inflammation. While this would argue against the use of CysLT antagonists in the treatment of AEE, further studies into the expression of the CysLT receptor itself are needed.

Nocturnal acid breakthrough in children with reflux esophagitis taking proton pump inhibitors.

OBJECTIVES: We aimed to determine if nocturnal acid breakthrough occurs in children receiving proton pump inhibitors for reflux esophagitis, and to compare the healing of esophagitis in children with nocturnal acid breakthrough receiving proton pump inhibitors +/- ranitidine. METHODS: This is a prospective, double-blind study. Endoscopic and histologic esophagitis were scored 0-4 and 0-3, respectively. Patients were treated with a proton pump inhibitor twice daily and esophagogastric pH monitoring was performed at week 3. Patients with nocturnal acid breakthrough were randomized. One group received ranitidine and the other received placebo at bedtime in addition to proton pump inhibitor therapy. Endoscopy was performed on all patients (with pH monitoring on patients with nocturnal acid breakthrough) during the 17th week of therapy. RESULTS: We enrolled 18 patients, ages 1 to 13 years (mean = 10.3 years). Mean baseline endoscopic and histologic scores were 3.1 +/- 1.4 and 1.8 +/- 0.7, respectively. Mean dose of proton pump inhibitor was 1.3 mg/kg +/- 0.6. Nocturnal acid breakthrough was documented in 16/18 (89%) patients. Seven patients received ranitidine and 9 received placebo. The reflux index improved: mean of 14.3 at baseline, 2.0 at week 3 (P = 0.0001), and 5.1 at week 17 (P = 0.09). Nocturnal acid breakthrough persisted in 9/12 (75%) patients, 3 of whom received ranitidine at bedtime. Esophagitis improved in all patients following therapy: mean endoscopy and histology scores were 1.6 +/- 1.8 (P = 0.0020) and 0.8 +/- 0.9 (P = 0.0013), respectively. Symptoms significantly improved from a mean score of 2.0 at baseline to 0.4 at week 17 (P = 0.0001). CONCLUSIONS: Nocturnal acid breakthrough is common in pediatric patients treated with proton pump inhibitors. Reflux index remains normal in spite of nocturnal acid breakthrough. Symptoms and esophagitis continued to improve during therapy in spite of nocturnal acid breakthrough. There appears to be no additional benefit to supplementation with ranitidine at bedtime.

Esophageal diverticulum: a complication of histoplasmosis in children.

We report three boys, ages 8 to 14 years, who experienced dysphagia or chest pain while eating. In each patient, contrast esophagrams or esophagogastroduodenoscopy (EGD) demonstrated mid-esophageal traction diverticula, and serologic findings were compatible with acute or recent histoplasmosis. Diverticula appear to result from esophageal traction induced by inflammatory changes in adjacent infected lymph nodes. Antifungal and anti-inflammatory therapies were individualized in each case; all patients recovered fully.

Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography in children: a large series report.

OBJECTIVES: Our goal is to evaluate the indications, findings, therapies, safety, and technical success of endoscopic retrograde cholangiopancreatography (ERCP) in children. METHODS: Our database was searched for patients 17 years of age or younger undergoing ERCP between January 1994 and March 2003. Additional information was obtained by chart review. The safety and technical success of ERCP were examined. Complications were classified by the consensus criteria. RESULTS: A total of 245 patients (95 M, 150 F; mean age 12.3 years) underwent 329 examinations. Indications included biliary pathology (n = 93), pancreatic pathology (n = 111), and chronic abdominal pain of suspected biliary or pancreatic origin (n = 41). The ERCP findings were bile duct stone(s) (n = 29), benign biliary stricture (n = 19), primary sclerosing cholangitis (n = 7), anomalous pancreaticobiliary union (n = 8), choledochal cyst (n = 5), bile duct leak (n = 6), malignant biliary stricture (n = 2), biliary atresia (n = 1), chronic pancreatitis (n = 44), pancreas divisum (n = 26), pancreatic duct stricture with (n = 6) or without (n = 9) leak, pancreatic tumor (n = 1), periampullary adenoma (n = 2), and sphincter of Oddi dysfunction (n = 65). Endoscopic therapies were performed in 71% of the procedures and included sphincterotomy, stone extraction, stricture dilation, endoprosthesis placement, snare papillectomy, and cystoduodenostomy. Thirty-two (9.7%) post-ERCP complications occurred and included cholangitis in 1 patient and pancreatitis in 31. The pancreatitis was graded mild in 24, moderate in 5, and severe in 2. No mortality related to ERCP occurred. CONCLUSIONS: Diagnostic and therapeutic ERCP results are similar in children and adults except for a lower incidence of malignant disease in children. Technical success rates are high. However, ERCP-related pancreatitis is not uncommon, and the risk and benefits should be carefully reviewed before proceeding. Outcome data are necessary and is currently being accumulated at our institution.