Prolonged duration of response to infliximab in early but not late pediatric Crohn's disease.

OBJECTIVES: Tumor necrosis factor-alpha plays a central role in chronic intestinal inflammation of Crohn's disease. Targeting this cytokine with the chimeric monoclonal antibody infliximab has emerged as an effective form of therapy in adult Crohn's disease patients. We sought to determine whether infliximab treatment would benefit pediatric patients with medically refractory Crohn's disease. We also assessed the duration of response, comparing children with early disease to children with long-standing (late) Crohn's disease. METHODS: Fifteen consecutive children (mean age 12.8 +/- 3.2 yr) with medically refractory Crohn's disease were enrolled in a prospective, open-label trial of a single, 5-mg/kg infliximab intravenous infusion. Medically refractory disease was defined as an inability to taper steroids, lack of response to immunomodulator therapy over 4 months, and active disease as measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Primary endpoints included measurements of disease activity (PCDAI), steroid use, and duration of clinical response. RESULTS: In all, 14/15 children (94%) improved after infliximab infusion, with a significant decrease of both PCDAI and daily steroid use by 4 wk. Ten patients (67%) achieved complete remission by 10 wk. Among the 14 patients who responded, three of six children (50%) with early disease maintained clinical response through the 12-month trial period, compared to none of eight children with late disease. There were no serious complications associated with the use of infliximab in any of the patients. CONCLUSIONS: Infliximab is safe and effective in the short-term treatment of medically refractory pediatric Crohn's disease. More importantly, there is a remarkably prolonged duration of response after infliximab therapy in children with early compared to late Crohn's disease.

Esophageal biopsy does not predict clinical outcome after percutaneous endoscopic gastrostomy in children.

Clinically symptomatic gastroesophageal reflux may occur after percutaneous endoscopic gastrostomy (PEG). Preoperative evaluation for gastroesophageal reflux does not reliably predict those individuals who will develop reflux unresponsive to medical management after PEG. Esophageal histology at the time of PEG might be used to identify patients at risk for developing intractable gastroesophageal reflux. The study aim was to correlate the clinical outcome after PEG with esophageal histology at the time of PEG insertion. A retrospective review of 68 consecutive children who had an esophageal biopsy obtained at the time of PEG insertion was undertaken. Preoperative evaluation, esophageal histology, and clinical outcomes were compared. Preoperative gastroesophageal reflux was present in 23% of upper gastrointestinal series performed, in 10% of pH probe studies, and in 29% of reflux scans. Histology was normal in 57% of esophageal biopsies obtained at the time of PEG insertion. Symptomatic gastroesophageal reflux requiring antireflux surgery or conversion to gastrojejunostomy developed in 10% of patients after PEG placement. Only one of these patients had esophagitis on biopsy. In conclusion, preoperative esophageal histology does not reliably predict the development of symptomatic gastroesophageal reflux after PEG placement.

Colonic motility in children with repaired imperforate anus.

Following surgical correction of imperforate anus, voluntary bowel control is frequently poor because of abnormal anorectal function. Using colonic manometry we investigated the role of colonic motility in the pathogenesis of fecal soiling in children following imperforate anus repair. Thirteen children with repaired imperforate anus and fecal soiling underwent motility testing 2-12 years after anoplasty. All had fecal incontinence unresponsive to conventional medical treatment. Colonic manometry was performed using water-perfused catheters. Anorectal manometry was undertaken in 10 patients. Motility study results, treatment and outcomes were compared. All patients had high-amplitude propagating contractions (HAPCs) with an average of 80% propagation into the neorectum. There was no correlation between HAPC number or morphology and any variable. Internal anal sphincter resting pressure was low in 6/10 patients. Relaxation of the internal anal sphincter was present in 6/10 children. Only 1 of 5 patients able to cooperate was capable of generating a normal maximal squeeze pressure. Therapeutic regimens were changed in 11 patients with clinical improvement in five. Fecal soiling in patients with repaired imperforate anus is a multifactorial problem including propagation of excessive numbers of HAPCs into the neorectum as well as internal anal sphincter dysfunction. Colonic manometry in conjunction with anorectal manometry aids in the understanding of the pathophysiology of fecal soiling and guides clinical management in children with repaired imperforate anus.

Electrogastrography in gastrostomy-tube-fed children.

Following gastrostomy tube placement some children develop gagging, retching, vomiting, pain, or irritability during feedings. Conventional medical management is not always successful. It is possible that intolerance of gastrostomy tube feedings reflects an underlying motility disorder of the foregut. The study aim was to determine whether children with gastrostomy tube feeding difficulties demonstrate abnormal gastric electrical control activity as measured by electrogastrography. Cutaneous electrogastrography of interpretable quality was performed in 25 feeding-tolerant and 23 feeding-intolerant children less than 10 years of age. Dominant frequencies, rhythm indices, and postprandial power measurements were recorded during the fasting and postprandial periods. Differences between groups were compared using the Student's t test. The groups were similar in method of gastrostomy tube placement, antireflux surgery, neurological impairment, duration of gastrostomy feeding dependence, formula type, volume, and administration. The feeding-tolerant group was significantly older (P<0.01). There were no significant differences between groups in the mean dominant frequencies or rhythm indices. The feeding-intolerant children had a mean postprandial power change that was significantly lower than that of the feeding tolerant group (P<0.003), although overlap was present. Children who are intolerant of gastrostomy tube feeding have an abnormal postprandial power decrease. EGG dominant frequency and rhythm indices are not predictive of gastrostomy feeding tolerance in predominantly neurologically impaired children.

Presenting symptoms and diagnostic lag in children with inflammatory bowel disease.

Presenting symptoms and their duration may affect the time that elapses prior to definitive diagnosis of inflammatory bowel disease (IBD). This study was undertaken to determine the mean duration of presenting symptoms and diagnostic lag in children with IBD. The medical records of all patients less than 19 years of age diagnosed with IBD at the pediatric gastroenterology clinic of Children's Hospital of Wisconsin between 1990-1995 were reviewed. The age at diagnosis, gender, presenting symptoms and duration, disease location, and diagnostic lag were analyzed. There were 91 children (49 male) diagnosed with IBD. Crohn's disease (CD) was diagnosed in 58, ulcerative colitis (UC) in 24, and indeterminate colitis in 9. The mean ages at diagnosis were 11.4 years for CD, 9.7 years for UC, and 7.8 years for indeterminate colitis. The most frequent presenting symptoms were abdominal pain, diarrhea, hematochezia, and weight loss. The average lag in diagnosis of CD was 7.1 months, which varied by disease location: small intestine 10.5 months, ileocolonic 7.5 months, and colonic 6.4 months. The average lag in diagnosis was 6.7 months for UC and 14 months for indeterminate colitis. Children presenting with growth failure had the longest diagnostic lag. (a) The elapsed time between symptom onset and the diagnosis of CD has decreased. (b) The diagnostic lag in CD decreases with distal colonic involvement. (c) Following onset of symptoms UC was diagnosed only slightly more rapidly than CD.