Prevalence of Barrett Esophagus in Adolescents and Young Adults With Esophageal Atresia.

OBJECTIVE: To study the prevalence of Barrett esophagus (BE) (gastric and/or intestinal metaplasia) in adolescents treated for esophageal atresia (EA). SUMMARY OF BACKGROUND DATA: EA patients are at high risk of BE. METHODS: This multicenter prospective study included EA patients aged 15 to 19 years. All eligible patients were proposed an upper endoscopy with multistaged esophageal biopsies under general anesthesia. Histological suspicion of metaplasia was confirmed centrally. RESULTS: One hundred twenty patients [mean age, 16.5 years (±1.4)] were included; 70% had been treated for gastroesophageal reflux disease (GERD) during infancy. At evaluation, 8% were undernourished, 41% had received antireflux surgery, and 41% presented with GERD symptoms, although only 28% were receiving medical treatment. Esophagitis was found at endoscopy in 34% and confirmed at histology in 67%. BE was suspected after endoscopy in 37% and was confirmed by histology for 43% of patients (50 gastric and 1 intestinal metaplasia). No endoscopic or histological anomalies were found at the anastomosis site. BE was not significantly related to clinical symptoms. In multivariate analysis, BE was associated with EA without fistula (P = 0.03), previous multiple antireflux surgery (P = 0.04), esophageal dilation (P = 0.04), suspicion of BE at endoscopy (P < 0.001), and histological esophagitis (P = 0.02). CONCLUSIONS: Patients with EA are at high risk of persistent GERD and BE. The development of BE is related to GERD history. Long-term systematic follow-up of the esophageal mucosa including multistaged biopsies is required, even in asymptomatic patients. (NCT02495051).

Intractable diarrhea with tufting enteropathy: a favorable outcome is possible.

BACKGROUND AND OBJECTIVE: Tufting enteropathy (TE) is a congenital abnormality of intestinal mucosa development characterized by severe intestinal failure requiring parenteral nutrition (PN) and, in some cases, small bowel transplantation. A few patients have had a more favorable outcome. The objective of this study was to evaluate possible correlations between histological lesion severity in duodenal biopsies and clinical outcomes in children with TE. PATIENTS AND METHODS: We retrospectively reviewed the records of patients diagnosed with TE between 1993 and 2003 at our institution based on intractable neonatal-onset diarrhea with prolonged dependence on PN and duodenal biopsy findings of villous atrophy, epithelial dysplasia with enterocyte dedifferentiation and disorganization (tufting) of the surface epithelium, and crypt abnormalities. The histological lesions were assessed semiquantitatively and compared with the clinical outcomes including dependence on PN. RESULTS: Seven children, all from consanguineous parents, were studied for a median of 6.5 years. Three were permanently weaned off PN and experienced normal growth without nutritional assistance. Initial biopsies in all 3 children showed severe diffuse histological lesions. At weaning off PN, 2 of these 3 patients had persistent, although less diffuse, histological lesions. CONCLUSIONS: Progressive weaning off PN is possible in some children with TE. In our experience, this favorable outcome was not predicted by histological lesion severity, although the lesions improved in some patients. New biomarkers for identifying the histological lesions and predicting the outcome would be useful.

Clinical and manometric characteristics of Allgrove syndrome.

OBJECTIVE: The association of adrenocorticotropic hormone (ACTH) insensitivity with achalasia and alacrimia (Allgrove syndrome, 3A) constitutes a rare multisystem disorder. Its evolution is not well known. The aim of this study was to describe clinical and esophageal manometric characteristics and outcomes in Allgrove syndrome. PATIENTS AND METHODS: This multicenter retrospective study compared clinical and manometric characteristics at diagnosis and on follow-up of 9 children presenting with 3A (mean age at diagnosis 7.1 years) with those of 9 children with idiopathic achalasia (IA) (mean age at diagnosis 8.3 years). RESULTS: At the time of diagnosis, 3 children with 3A presented with no digestive or respiratory signs because they were identified during a family screening; 1 remained asymptomatic 8 years later. ACTH levels were high in patients with 3A. All of the patients with IA were symptomatic at diagnosis. No significant difference was observed when comparing any of the manometric parameters of the first esophageal manometry of 3A with those of IA. Seven children with 3A were operated on using the Heller procedure, completed by pneumatic esophageal dilation in 2 of these 7. One patient with 3A was treated only by nifedipine. Failure of treatment was observed in 3 children with 3A and 1 child with IA, partial success in 4 with 3A and 1 with IA, and total success in 2 with 3A and 7 with IA (P < 0.03). Control manometry showed that in the 3A group, partial success after surgery was always associated with abnormally low or normal lower esophageal sphincter (LES) pressure, whereas failure after surgery was associated with high LES pressure. CONCLUSIONS: Our data showed that 3A presented a more severe course than IA despite presymptomatic diagnosis in cases of family screening. The high LES pressure noted in some patients with 3A is suggestive of a peculiar pattern in 3A affecting the LES and the lower part of the esophagus.

Incidence of autoimmune diseases in celiac disease: protective effect of the gluten-free diet.

BACKGROUND & AIMS: Celiac disease may be associated with autoimmune diseases. The aims of the present study were to determine in celiac patients which factors modulate the risk of autoimmune disease and to evaluate the effect of the gluten-free diet. METHODS: The occurrence of autoimmune disease and compliance to gluten-free diet were specified retrospectively in 924 celiac patients recruited from 27 French pediatric and adult gastroenterology centers. RESULTS: One or several autoimmune diseases had developed in 178 patients. The cumulative risk of autoimmune disease was 8.1% +/- 1% at age 15, and 15.7% +/- 1.5% at age 30. Factors associated with an increased risk were family history of autoimmunity (hazard ratio, 2.36; 95% confidence interval, 1.71-3.31) and diagnosis of celiac disease before 36 years of age (hazard ratio, 2.65; 95% confidence interval, 1.79-3.85). After diagnosis of celiac disease, 55 of 788 patients developed an autoimmune disease. The cumulative risk of subsequent autoimmune disease was lower in patients compliant to a gluten-free diet versus noncompliant patients (at 10 years, 6% +/- 2% vs 15.6% +/- 5.9%, respectively; P = .02). The incidence of autoimmune diseases was 5.4 per 1000 patient-years during adherence to a gluten-free diet versus 11.3 per 1000 patient-years during nonadherence to the diet (P = .002). Results were similar in both the pediatric and the adult populations. CONCLUSIONS: Celiac patients most at risk for autoimmune disease are those diagnosed early in life and having a family history of autoimmunity. The gluten-free diet has a protective effect.

Efficacy and tolerance of infliximab in children and adolescents with Crohn's disease.

Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn's disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3-17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8-7.3) of infliximab during a median time period of 4 months (1-17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey-Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn's disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment.

Natural history of Crohn's disease: comparison between childhood- and adult-onset disease.

BACKGROUND: Childhood-onset Crohn's disease (CD) might reflect a more severe form of disease. To test this hypothesis we analyzed the long-term natural history of CD in an adult cohort of patients with childhood-onset compared to adult-onset CD. METHODS: We selected 206 childhood-onset CD patients among 2992 adult patients with a diagnosis of CD established before December 31, 2000. Disease characteristics were prospectively assessed during follow-up until December 2007 and compared to adult-onset CD patients matched 2 to 1 on gender, year of CD diagnosis, and disease location. RESULTS: Compared to adult-onset CD, patients with childhood-onset CD were more likely to have a severe disease, with an increased year-by-year disease activity index (37% of patient-years in childhood-onset group versus 31% in the adult-onset group, P < 0.001). Immunosuppressant requirement was also increased with a 10-year cumulative risk of 54 +/- 3% in childhood-onset CD group versus 45 +/- 2%, in the adult-onset CD group (P < 0.001). Cumulative risks of stricturing and penetrating complications and surgical resections were not statistically different between groups. Accordingly, these events occurred at a younger age in the childhood-onset CD group. At the age of 30 years the actuarial risk of having undergone an extensive intestinal resection was 48 +/- 5% in the childhood-onset group versus 14 +/- 2% in the adult-onset group (P < 0.001). CONCLUSIONS: Patients with childhood-onset CD exhibit a more active disease and require more immunosuppressive therapy. This feature is observed irrespective of the disease location, suggesting an intrinsic more severe phenotype.

Efficacy of infliximab in pediatric Crohn's disease: a randomized multicenter open-label trial comparing scheduled to on demand maintenance therapy.

BACKGROUND: Infliximab (IFX) is efficacious in inducing remission in severe forms of pediatric Crohn's disease (CD). Adult studies indicate that IFX is also safe and well tolerated as maintenance therapy. The present study aimed to evaluate in a prospective manner the efficacy and safety of IFX as maintenance therapy of severe pediatric CD comparing scheduled and "on demand" treatment strategies. METHODS: Forty children with CD (nonpenetrating, nonstricturing as well as penetrating forms, mean age: 13.9 +/- 2.2 years) with a severe flare-up (Harvey-Bradshaw Index [HBI] > or =5, erythrocyte sedimentation rate [ESR] >20 mm/h) despite well-conducted immunomodulator therapy (n = 36 azathioprine, n = 1 mercaptopurine, n = 3 methotrexate) combined with steroids were included in this randomized, multicenter, open-label study. Three IFX infusions (5 mg/kg) were administered at week (W)0/W2/W6. At W10, clinical remission (HBI <5) and steroid withdrawal were analyzed and IFX responders were randomized to maintenance therapy over 1 year: group A, scheduled every 2 months; group B, "on demand" on relapse. RESULTS: In all, 34/40 children came into remission during IFX induction therapy (HBI: 6.7 +/- 2.5 (WO) vs. 1.1 +/- 1.5 (W10); P < 0.001). At the end of phase 2, 15/18 (83%) patients were in remission in group A compared to 8/13 (61%) children in group B (P < 0.01), with a mean HBI of 0.5 versus 3.2 points (group A versus B, P = 0.011). In group A, 3/13 (23.1%) children experienced a relapse compared to 11/12 (92%) children in group B. No severe adverse event occurred during this trial. CONCLUSIONS: IFX is well tolerated and safe as maintenance therapy for pediatric CD, with a clear advantage when used on a scheduled 2-month basis compared to an "on demand" basis.