Therapeutic applications of octreotide in pediatric patients

Background/Aim: We report our experience with the use of octreotide as primary or adjunctive therapy in children with various gastrointestinal disorders. Patients and Methods: A pharmacy database identified patients who received octreotide for gastrointestinal diseases. Indications for octreotide use, dosing, effectiveness, and adverse events were evaluated by chart review. Results: A total of 21 patients (12 males), aged 1 month to 13 years, were evaluated. Eleven received octreotide for massive gastrointestinal bleeding caused by portal hypertension-induced lesions (n=7), typhlitis (1), Meckel′s diverticulum (1), and indefinite source (2). Blood transfusion requirements were reduced from 23±9 mL/kg (mean±SD) to 8±15 mL/kg (P<0.01). Four patients with pancreatic pseudocyst and/or ascites received octreotide over 14.0±5.7 days in 2 patients. In 3 children, pancreatic pseudocyst resolved in 12±2 days and pancreatic ascites resolved in 7 days in 2. Three patients with chylothorax received octreotide for 14±7 days with complete resolution in each. Two infants with chronic diarrhea received octreotide over 11±4.2 months. Stool output decreased from 85±21 mL/kg/day to 28±18 mL/kg/day, 3 months after initiation of octreotide. The child with dumping syndrome responded to octreotide in a week. Adverse events developed in 4 patients: Q-T interval prolongation and ventricular fibrillation, hyperglycemia, growth hormone deficiency, and hypertension. Conclusion: Octreotide provides a valuable addition to the therapeutic armamentum of the pediatric gastroenterologist for a wide variety of disorders. Serious adverse events may occur and patients must be closely monitored

The burden of large and small duct primary sclerosing cholangitis in adults and children: A population-based analysis

OBJECTIVES: The epidemiology of primary sclerosing cholangitis (PSC) has been incompletely assessed by population-based studies. We therefore conducted a population-based study to determine: (a) incidence rates of large and small duct PSC in adults and children, (b) the risk of inflammatory bowel disease on developing PSC, and (c) patterns of clinical presentation with the advent of magnetic resonance cholangiopancreatography (MRCP). METHODS: All residents of the Calgary Health Region diagnosed with PSC between 2000 and 2005 were identified by medical records, endoscopic, diagnostic imaging, and pathology databases. Demographic and clinical information were obtained. Incidence rates were determined and risks associated with PSC were reported as rate ratios (RR) with 95% confidence intervals (CI). RESULTS: Forty-nine PSC patients were identified for an age- and gender-adjusted annual incidence rate of 0.92 cases per 100,000 person-years. The incidence of small duct PSC was 0.15/100,000. In children the incidence rate was 0.23/100,000 compared with 1.11/100,000 in adults. PSC risk was similar in Crohn's disease (CD; RR 220.0, 95% CI 132.4-343.7) and ulcerative colitis (UC; RR 212.4, 95% CI 116.1-356.5). Autoimmune hepatitis overlap was noted in 10% of cases. MRCP diagnosed large duct PSC in one-third of cases. Delay in diagnosis was common (median 8.4 months). A minority had complications at diagnosis: cholangitis (6.1%), pancreatitis (4.1%), and cirrhosis (4.1%). CONCLUSIONS: Pediatric cases and small duct PSC are less common than adult large duct PSC. Surprisingly, the risk of developing PSC in UC and CD was similar. Autoimmune hepatitis overlap was noted in a significant minority of cases.</p

A Pilot Study Examining the Relationship among Crohn Disease Activity, Glucagon-Like Peptide-2 Signalling and Intestinal Function in Pediatric Patients

BACKGROUND/OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release is triggered by nutrient contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2 release

Consumption of pure oats by individuals with celiac disease: A position statement by the Canadian Celiac Association

The treatment of celiac disease is a strict adherence to a gluten-free diet for life. In the past, oats were considered to be toxic to individuals with celiac disease and were not allowed in a gluten-free diet. However, recent evidence suggests that oats that are pure and uncontaminated with other gluten-containing grains, if taken in limited quantities, are safe for most individuals with celiac disease. For adults, up to 70 g (1/2 to 3/4 cup) of oats per day and for children, up to 25 g (1/4 cup) per day are safe to consume. These oats and oat products must fulfill the standards for a gluten-free diet set by the Canadian Food Inspection Agency and Health Canada. The Canadian Celiac Association, in consultation with Health Canada, Agriculture & Agri-Food Canada and the Canadian Food Inspection Agency, has established requirements for growing, processing, and purity testing and labelling of pure oats. These strategies have led to the production of pure, uncontaminated oats for the first time in Canada. Oats and oat products that are safe for consumption by individuals with celiac disease and dermatitis herpetiformis are now commercially available in Canada

Intestinal Permeability before and after Ibuprofen in Families of Children with Crohn’s Disease

BACKGROUND: Members of a subset of first-degree relatives of adults with Crohn’s disease have been shown to have an increased baseline intestinal permeability and/or an exaggerated increase in intestinal permeability after the administration of acetylsalicylic acid

Intestinal permeability before and after ibuprofen in families of children with Crohn’s disease

BACKGROUND: Members of a subset of first-degree relatives of adults with Crohn&apos;s disease have been shown to have an increased baseline intestinal permeability and/or an exaggerated increase in intestinal permeability after the administration of acetylsalicylic acid. PURPOSE: To determine intestinal permeability in unaffected first-degree relatives of children with Crohn&apos;s disease before and after the administration of an ibuprofen challenge. METHODS: Lactulose-mannitol ratios, a measure of intestinal permeability, were determined in 14 healthy control families (41 subjects) and 14 families with a child with Crohn&apos;s disease (36 relatives, 14 probands) before and after ingestion of ibuprofen. An upper reference limit was defined using the control group as mean ± 2 SD. RESULTS: The proportion of healthy, first-degree relatives with an exaggerated response to ibuprofen (20%, 95% CI 7% to 33%) was significantly higher than controls (P=0.003). The exaggerated response was more common among siblings than among parents of pediatric probands. CONCLUSIONS: Members of a subset of first-degree relatives of children with Crohn&apos;s disease have an exaggerated increase in intestinal permeability after ibuprofen ingestion. These findings are compatible with there being a genetic link between abnormalities of intestinal permeability and Crohn&apos;s disease. Pediatrics, Health Science Centre, 3330 Hospital Drive NW, Calgary, Received for publication March 11, 1998. Accepted July 7, 1998 ORIGINAL ARTICLE T he etiology of Crohn&apos;s disease remains unknown; however, genetic and environmental factors are believed to contribute to the development of the disease. The familial aggregation of inflammatory bowel disease (Crohn&apos;s disease and/or ulcerative colitis), which may be attributed to either genetic or environmental factors, is well recognized, with a 5% to 20% likelihood of finding inflammatory bowel disease in relatives of a proband (1-5). A recent survey determining familial empirical risk of inflammatory bowel disease estimated that between 5% and 8% of first-degree relatives of affected patients will develop Crohn&apos;s disease in their lifetime (6). One approach to the identification of a genetic cause of a given disorder is to search for clinical or phenotypic markers, the occurence of which may mark the presence of specific candidate genes that might predispose to the development of the disorder -in this instance, Crohn&apos;s disease. Hollander et al The objectives of the present study were to measure intestinal permeability before and after an ibuprofen challenge in families (first-degree relatives) of children with Crohn&apos;s disease and to examine concordance in permeability results among family members. Children were studied because the familial aggregation of Crohn&apos;s disease has been shown to be associated with a lower age of onset in affected individuals of successive generations (19-22). Studies of affected parent-child pairs have shown that parents are between five and 15 years older than children at onset SUBJECTS AND METHODS Subjects: The study was approved by the Conjoint Medical Regional Ethics Board representing the University of Calgary and the Calgary Regional Health Association, and written informed consent was obtained from participating families. Of all the families of children with Crohn&apos;s disease followed at the Gastroenterology Clinic at Alberta Children&apos;s Hospital, 31 met the inclusion criteria of having a child with Crohn&apos;s disease in clinical remission, assessed by the attending pediatric gastroenterologist using a previously validated pediatric Crohn&apos;s disease activity index (25). Seven families refused to participate because the proband did not agree to do the test. Among the 24 remaining families who gave informed consent, 14 children (less than 18 years of age) with Crohn&apos;s disease and their complete families (36 first-degree relatives of children with Crohn&apos;s disease) completed the permeability studies. Fourteen healthy families (recruited from the out-patient fracture clinic and the families of staff at Alberta Children&apos;s Hospital) comprised the control group (41 family members). All relatives and controls were free of gastrointestinal symptoms. Asymptomatic relatives and controls were not investigated to identify undiagnosed Crohn&apos;s disease. Exclusion criteria for the families of healthy control children or families with an index child affected by Crohn&apos;s disease were regular use of ASA/NSAID (at least once a week), allergy or contraindication to ibuprofen, diabetes mellitus, renal insufficiency and, for children with Crohn&apos;s disease, clinical relapse. Study protocol: Subjects were instructed not to consume alcohol or NSAID for at least three days before permeabil- Technilab) and mannitol 2 g (BDH Chemicals Inc) in 100 mL of water (osmolarity 273 osmol/L). Children received 2 mL/kg (maximum 100 mL) of the test solution (lactulose 0.1 g/kg and mannitol 0.04 g/kg) and adults 100 mL. Subjects voided before drinking the test solution and then collected all urine including the first morning void in containers with 5 mL of 10% thymol in methanol. Subjects underwent two permeability tests -a baseline and a postibuprofen test. The second test was done one to five days after the baseline test. A pilot study in adults determined that an 800 mg dose of ibuprofen produced a percentage change in lactolose-mannitol (LM) ratio similar to that reported in response to ASA (18). On this basis, an oral dose of ibuprofen (adults: 800 mg; children 10 mg/kg to a maximum dose of 800 mg) was administered, and 1 h later subjects consumed the test solution and collected urine in an identical fashion to that for the baseline permeability test. One child with Crohn&apos;s disease and one subject in the relatives group had an intolerance to NSAID and did not perform the ibuprofen challenge. Analytical methods: Urine samples were kept refrigerated until analysis. Urine samples (10 mL) were deionized by adding 1 g of a 1:1.5 (wt/wt) mixture of Amberlite IR-120 and IRA-400 resin (BDH Chemicals Inc). Following centrifugation at 700 g for 10 mins, the supernatant was filtered through a 40 µm/L Millipore filter (Millipore, Massachusetts). Samples were separated on a Dionex MA-1 anion exchange column in a Dionex HPLC (Dionex) at room temperature using 500 mmol/L sodium hydroxide as the isocratic mobile phase. Peak identification was accomplished with the use of authentic standards and detected using pulsed amperometric electrochemical detection on a gold electrode. Samples were diluted as necessary after addition of cellobiose as an internal standard. Sample concentrations were quantified using linear interpolation between concentrations of known standards at multiple concentrations. All samples were diluted so that concentrations of interest fell within the range of the standards. The fractional excretion of each probe was determined by calculating the proportion of the ingested probe that was excreted in the urine. The LM ratio was obtained by dividing the fractional excretion of lactulose by the fractional excretion of mannitol. The LM ratio represents the measure of intestinal permeability. To account for the baseline level of intestinal permeability in each individual, the percentage change in LM ratio after ibuprofen was used as the main measure of interest, reflecting the response to the NSAID challenge. This ratio was calculated as follows: Percentage change in LM ratio Statistical analysis: Analyses were performed using the statistical software Stata 5.0 (Stata Corporation, Texas). All statistical tests are two-sided with an alpha level of 0.05. Descriptive statistics were performed on baseline characteristics of children with Crohn&apos;s disease and their firstdegree relatives, and controls. Baseline LM ratios did not appear to have a normal distribution and are, therefore, expressed as median and range. The percentage change in LM ratio postibuprofen was normally distributed, and data are means ± SE. Baseline LM ratios were compared among groups by using the Mann-Whitney U test. Changes in LM ratio postibuprofen were compared among study groups by using t tests. An upper reference limit was defined as mean ± 2 SD of the data from the control population. For baseCan J Gastroenterol Vol 13 No 1 January/February 1999 33 Intestinal permeability and Crohn&apos;s disease Percentage change in LM ratio, mean (SE) 38 RESULTS Permeability tests were well tolerated, and none of the children with Crohn&apos;s disease completing the ibuprofen challenge had a flare up of the disease attributable to the test. Demographic characteristics of study subjects are shown in Children in both the control and relative groups appeared to have higher baseline LM ratios than adults; however, this difference did not reach statistical significance. If children and adults were considered together, the median baseline LM ratio in relatives (0.0176) was similar to that in controls (0.0165). The median baseline LM ratio in children with Crohn&apos;s disease (0.0271) was significantly higher than in control children (P&lt;0.001). One of 41 subjects in the control group (2%) and two of 36 in the relatives group (6%) had a baseline LM ratio above the upper reference limit. Baseline intestinal permeability was not significantly different between smokers and nonsmokers. No subject in the control group and one of 13 (8%) subjects in the group of children with Crohn&apos;s disease (8%) had a response to ibuprofen above the upper reference limit. Seven relatives (three parents and four siblings) had a percentage increase in LM ratio postibuprofen above the upper reference limit. Thus, the proportion of relatives with an exaggerated response to ibuprofen (seven of 35 [20%], 95% CI 7% to 33%) was significantly higher than that in controls (P=0.003). When smokers (four adults and no children in the group of relatives were current smokers) were excluded from the analysis, the proportion of relatives with an exaggerated response to ibuprofen remained higher than that in controls (16% versus 0%, respectively; Fisher&apos;s exact test P=0.06). In the group of relatives of children with Crohn&apos;s disease, the exaggerated response to ibuprofen was more frequent among siblings (four of 13 [31%]) than among their parents (three of 22 [14%]), and the children appeared to have a greater percentage change in LM ratio postibuprofen than adults (105% versus 44% respectively), but this difference did not reach statistical significance. The mean percentage change in LM ratio postibuprofen in relatives (mean 66%, SE 20%) and in children with Crohn&apos;s disease (mean 81%, SE 43%) was higher than in the control group (mean 35%, SE 7%); however, these differences did not reach statistical significance

Biliary Atresia: The Canadian Experience

To determine the outcomes of Canadian children with biliary atresia. Health records of infants born in Canada between January 1, 1985 and December 31, 1995 (ERA I) and between January 1, 1996 and December 31, 2002 (ERA II) who were diagnosed with biliary atresia at a university center were reviewed. 349 patients were identified. Median patient age at time of the Kasai operation was 55 days. Median age at last follow-up was 70 months. The 4-year patient survival rate was 81% (ERA I = 74%; ERA II = 82%; P = not significant [NS]). Kaplan-Meier survival curves for patients undergoing the Kasai operation at age ≤30, 31 to 90, and >90 days showed 49%, 36%, and 23%, respectively, were alive with their native liver at 4 years ( P < .0001). This difference continued through 10 years. The 2- and 4-year post-Kasai operation native liver survival rates were 47% and 35% for ERA I and 46% and 39% for ERA II ( P = NS). A total of 210 patients (60%) underwent liver transplantation; the 4-year transplantation survival rate was 82% (ERA I = 83%, ERA II = 82%; P = NS). This is the largest outcome series of North American children with biliary atresia at a time when liver transplantation was available. Results in each era were similar. Late referral remains problematic; policies to ensure timely diagnosis are required. Nevertheless, outcomes in Canada are comparable to those reported elsewhere