Evaluation of guidelines for management of familial adenomatous polyposis in a multicenter pediatric cohort.

OBJECTIVE: To retrospectively assess, in a pediatric multicenter cohort, guidelines for the management of familial adenomatous polyposis (FAP). METHODS: Ten centers from the French-speaking Pediatric Gastroenterology Hepatology and Nutrition Group provided follow-up data on patients up to 18 years of age. Clinical records, genetic test results, endoscopy with histopathology examination, and therapeutic modalities were reviewed. RESULTS: A total of 70 children from 47 families were included. When initial consultation resulted from a surveillance program because of an affected family member, 12 of 59 children were already symptomatic. Among 11 patients whose initial consultation was based only on symptoms, families were unaware at the time of a familial FAP history for 7 children, whereas only 4 cases were sporadic. A panel of 27 different pathogenic adenomatous polyposis coli (APC) germ-line mutations and large genomic deletions were identified in 43 families. Extracolonic manifestations were found in half of the patients. As part of the standard practice for initial screening, the entire cohort underwent colonoscopy, which revealed adenoma above an intact rectosigmoid in 8 cases. Prophylactic colectomy was performed in 42 cases; high-grade dysplastic adenoma and 1 invasive carcinoma were detected in 6 children. For timing of surgery, indications were in accordance with recent international guidelines. CONCLUSIONS: Defining optimal screening and therapeutic modalities in pediatric FAP cohorts is a challenge. Specific advice for genetic screening, endoscopy surveillance, and type of surgery based on recent guidelines is recommended.

Aspergillus fumigatus endocarditis in a pediatric liver transplant recipient: favorable outcome without cardiac surgery.

Transplant recipients are very susceptible to invasive aspergillosis, which increases mortality rate. Disseminated aspergillosis in the liver transplant recipient can affect virtually any organ and endocarditis is often lethal despite cardiac surgery and antifungal therapy. We report the case of a eight-month-old girl who presented with Aspergillus fumigatus endocarditis 18 days after liver transplantation that was successfully treated by a combination of antifungal drugs associated to a low dosage of immunosuppressive therapy.

Upper gastrointestinal complications associated with NSAIDs in children.

OBJECTIVE: To analyse serious upper gastrointestinal (UGI) complications associated with non-salicylate non-steroidal anti-inflammatory drugs (NSAIDs) in children. METHODS: All serious UGI complications associated with non-salicylate NSAIDs approved in France to treat moderate pain or fever in children, spontaneously reported to the French Pharmacovigilance system or to the companies, between the launching of each study drug in France to December 31, 2000. RESULTS: Serious UGI complications were reported in 61 children aged from 11 months to 15 years during treatment with niflumic acid (27), ibuprofen (23) and tiaprofenic acid (11). No case was reported with ketoprofen. UGI manifestations were UGI bleeding (15) and 46 gastrointestinal symptoms with endoscopic lesions i.e. gastritis (18), gastric ulcer (13), duodenal ulcer (7), duodenitis (4) and oesophageal ulcer (4). NSAID was combined with a salicylate in 36% of cases, given by the parents in self medication in 6.6% of cases and used outside its product licence in 33.8% of cases. CONCLUSION: NSAIDs used in children for fever or moderate pain are associated with a risk of serious UGI complications which increases with length, dose and association with a salicylate.

Characteristics of inflammatory bowel disease with onset during the first year of life.

BACKGROUND: Inflammatory bowel disease (IBD) is recognized in young children, however, only rare data on onset and evolution are available in children younger than 1 year. In the present clinical study, we aimed to analyze characteristics and clinical course of children with very early onset IBD. We were particularly interested in the relationship between bacterial infections and the use of antibiotics before the onset of IBD. PATIENTS AND METHODS: The IBD database of Necker-Enfants-Malades-Hospital was screened for patients with IBD with disease onset during the first year of life and a follow-up of at least 2.5 years. Ten patients were identified during the period 1996-2002. RESULTS: All patients presented with rectal bleeding and had colonic involvement. Four patients had definitive diagnosis of Crohn disease; ulcerative or indeterminate colitis was seen in 2 and 4 children, respectively. Five of the patients had a positive history of neonatal or early-onset bacterial infection with use of antibiotics before onset of IBD, 4 patients were still breastfed and 3 just weaned when GI symptoms started. Seven patients had a severe onset of disease requiring bowel rest, parenteral nutrition and steroid medication, followed by azathioprine or cyclosporine medication. Surgery was necessary in 3 of 10 patients. Disease relapses were frequent and observed in 8 of 10 children. DISCUSSION: Very early onset IBD may reflect a subgroup of patients characterized by a particular sensitivity to modifications of the intestinal flora. Neonatal IBD was most often severe in presentation and evolution.

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.

Contribution of capsule endoscopy to Peutz-Jeghers syndrome management in children.

BACKGROUND: Capsule endoscopy is recommended for children with Peutz-Jeghers syndrome as young as 8 years of age. Aim of our study was to evaluate the contribution of capsule endoscopy in managing risk of further obstructive complications. METHODS: A retrospective analysis of 27 children who received at least 1 capsule endoscopy was conducted. Peutz-Jeghers syndrome was diagnosed based on the presence of an STK11 gene mutation or on the association of a hamartoma with 2 of 3 criteria (family history, mucocutaneous pigmentation, small bowel polyposis). RESULTS: Thirty-seven capsule endoscopies were performed in 27 patients. The median age at first endoscopy was 11.4 years (range, 5.4-20.9). Jejunal polyps were found in 72% and ileal polyps in 55% of capsules. The original recommendations were followed 20/30 times. Three gastroscopies, 4 colonoscopies, 7 double balloon enteroscopies and 1 intra-operative enteroscopy were performed after the capsules. These procedures revealed jejunal polyps in 9/9 cases (8/9 resected) and ileal polyps in 3/5 (all resected). One intussusception occurred 8.4 months after the capsule endoscopy and required surgical resection. CONCLUSION: Capsule endoscopy is easily feasible in Peutz Jeghers syndrome, but the practice of systematic and repeated procedures needs to be validated prospectively.

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.

Children's nutrition and health in adulthood.

Scientific and medical studies report that the environment, and particularly physical activity and the diet, changes the metabolic programming. A systematic review of size and growth during infancy supports conclusions with regard to preventing later obesity. Moreover, the correlation has been established between birth weight, arterial blood pressure, plasmatic lipid level, and cardiovascular mortality. The European Nutrition Committee has written new recommendations with lower protein levels. A lot of data support the application of blocking sensibilisation through intervention in pregnancy and lactation. Primary prevention is possible with breastfeeding for the first 4-6 months of life, particularly for high-risk allergic families. This is a priority for the national health program in France for controlling the increasing obesity.

Therapeutic strategies for idiopathic chylothorax.

STUDY OBJECTIVES: The objectives of the study were to present our institutional experience of idiopathic chylothorax in children and to propose therapeutic strategies. DESIGN: This was a retrospective, single-center study. PATIENTS: Patients were 6 children (4 boys, 2 girls) presenting with an idiopathic chylothorax diagnosed from the presence of a chylous pleural effusion with triglycerides greater than 1.2 mmol/L and a cellularity greater than 1000 cells/mL with a predominance of lymphocytes. RESULTS: Median age of onset was 7 years (range, 2-14 years). Initial symptoms included cough (n = 4), tachypnea (n = 4), asthenia (n = 5), abdominal pain (n = 2), and bronchitis (n = 1). Chest radiography showed 2 left, 2 right, and 2 bilateral pleural effusions. Serum biology assessment was normal in all children. Respiratory function assessment at diagnosis revealed a decrease in functional residual capacity in 3 children and a decrease in lung diffusing capacity in 2 children. Initially, all patients received a medium-chain triglyceride diet for 29 months (range, 10-50 months). Total parenteral nutrition was required for 4 patients (for 1-4 months), and somatostatin was tried in one child. Two children required pleuroperitoneal shunting, bilateral in one case. During the follow-up (median duration, 6 years; range, 2-16 years), chylothorax stabilized in all patients and 5 patients were able to return to a normal diet. CONCLUSION: A medium-chain triglyceride diet associated in some cases with total parenteral nutrition may stabilize idiopathic chylothorax in children. In cases where conservative treatment has failed, pleuroperitoneal shunting may be useful.