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Epidemiology of Constipation in Children and Adults
in these patients were seizure disorders (20%), acute lymphocytic leukemia (20%), and Crohn's disease (11%). One third of the patients had an additional etiology other than the medication known to be associated with pancreatitis. Steroids were the most common drug association, followed by valproic acid, mesalamine, and bactrim. Patients with a drugassociated etiology received twice as many CT scans (p=0.0002) and fewer ERCPs (p=0.006) than those with a non-drug-associated etiology. The drug-associated patients stayed in the hospital longer (p=0.0004) and were more likely to receive parenteral than oral feeding (p= 0.019). There was a higher frequency of valproic acid (p<0.05) in the younger age group (0-10 years) than the older age group (11-20 years) in both the total cohort of drugassociated cases as well as in those specific cases that had no concomitant pancreatitis etiology. Conclusion: We found that drug-associated acute pancreatitis is common in children. Onethird of cases have additional etiologies. Our study underscores the importance of considering drugs associated with pancreatitis as a possible cause even when other etiologies are identified.
Impact of Obesity on Pediatric Cholecystectomy Nitin Gupta, Aliza B. Solomon, Edmund Kessler Background: The prevalence of cholecystectomies in children is on the rise. The impact of obesity on gallbladder disease and surgical outcomes in adults is well documented; however, there is minimal data in the pediatric population. Obesity appears to be a risk factor in pediatric gallbladder disease leading to a parallel increase in cholecystectomies. Methods: A retrospective chart review was performed on patients who underwent cholecystectomies between the years 2005-2010. Data collected included age, sex, height, weight, Body Mass Index (BMI) percentiles, past medical history, indications, prior imaging, length of stay, complications, comorbidities and type of surgery. Results: Preliminary results of 58 records were reviewed. The mean age of patients was 17.8 years (range 8-21) and 82.8% were female. There were 26 in the normal weight (NW) group and 32 in the overweight (OW) (BMI >85%) group. 55% of the surgeries were performed on the OW group. The mean number of cholecystectomies was 11 per year and there was no increased incidence of cholecystectomy across 5 years. The indication for cholecystectomy did not differ between the groups. The length of stay for acute surgery was longer amongst the NW group with 3.2 days (range 1-13) compared to 2.5 days (range 1-9) for the OW group. More patients in NW group had associated comorbidities that contributed to hospital stay such as sickle cell disease, renal disease and congenital heart defects. The mean operative time was 132.9 minutes (range 79-213) in the NW group and 154.8 minutes (range 96-249) in the OW group. Conclusion: Although many pediatric patients undergoing cholecystectomy are obese, obesity may not necessarily be directly linked with an increased prevalence of surgery. Obesity did impact the mean operative time and further studies are needed to examine this data for causal relationship.
Mo1963 Understanding Clostridium difficile-Associated Disease (CDAD) in Children at a Tertiary Care Children's Hospital: A 6 Year Retrospective Study Rodrigo Rodrigues, Khaled Bittar, Hossein Salimnia, Mohammad El-Baba Background: Although the incidence rate of CDAD has reportedly increased in the adult patient population, there is fewer data on this disease in children. Clostridium difficile (CD) has been seen traditionally seen as nonpathogenic in young infants, but recent data has shown increasing burden of CDAD among this age group. A retrospective study was performed to determine the pattern of C. difficile infection in our hospital and compare our results with previous studies in search of a better understanding of the clinical and epidemiological features of CDAD in children. Methods: We conducted a retrospective cohort study that includes patients who visited/ admitted to our hospital between January 1, 2004 and December 31, 2009. Patient records that documented an assay positive for CD toxin were extracted from a database maintained by the clinical virology laboratory and reviewed to obtain information on demographic characteristics, history of hospital visits, prior antibiotic use, patient location at the time of the beginning of symptoms and co-morbidities. CDAD was defined as clinical symptoms, such as diarrhea with or without blood, in a patient whose stool specimen tested positive for CD toxin. Results: We identified 203 patients with CDAD. Over the 6 years of the study, there was a linear increase in the number of patients diagnosed with CD infection from 25 cases in 2004 to 47 in 2009. There were 92 (45.3%) females and 111 (54.7%) males. Seventy percent were younger than 7 years and 40% were under 2 years of age. One hundred and sixty three patients (80%) had some chronic medical condition. Hematologic/oncologic conditions had the highest number of positive cases 62/ 203 (30%), followed by gastrointestinal, neuromuscular and cardiac patients. About two thirds of the patients developed symptoms during hospitalization for other medical condition. 146 patients (72%) had history of previous antibiotic use. Conclusions: Our data has shown increased frequency of CDAD in children. We also found that symptomatic CD infection is common in young children less than two years of age. This may be due to an increase in the number of tests ordered and a diffusion of the awareness of CD as an important cause of gastroenteritis in hospitalized patients. Patients with chronic medical conditions, specially, hematologic/oncologic and chronic gastrointestinal diseases deserve a special attention and a lower threshold for diagnosis and treatment.
Mo1961 Sedated Percutaneous Endoscopic Gastrostomy (PEG) Placement in the Neonate Alex Green, Edward G. Shepherd, Steven H. Erdman Background: Nutrition support is a cornerstone therapy for premature and sick neonates. Long-term nutrition support is best achieved by gastrostomy tube (GT) which can be placed endoscopically (PEG) using bedside sedation or operatively under general anesthesia (GA). Controversy exists regarding the safest method of PEG placement in ill neonates who may be at particular risk of respiratory or airway complications relating to GA. To avoid such complications, bedside PEG placement with IV sedation has been utilized in our neonatal intensive care units (NICUs). This multidisciplinary approach emphasizes individualized patient assessment and the presence of a neonatologist for sedation and airway management. Patients/Methods: Charts of all infants who underwent bedside PEG in our NICUs from August 2006 to March 2010 were reviewed. Available demographic information, past medical history, nutritional status at time of procedure and up to one year after, procedure information (ASA scores, medications, respiratory status), and short- and long-term outcomes were collected and analyzed. Results: A total of 93 patients underwent bedside PEG placement during the review period. The mean age at placement was 17.4 weeks (2-60 weeks) with an adjusted gestational age of 48.4 weeks (17-84 weeks). The average weight at the time of the procedure was 4298 gm (2175-8040 gm). The patients had a number of underlying conditions including bronchopulmonary dysplasia (45%), genetic disease (26%), intraventricular hemorrhage (22%), and poor weight gain (20%). There were 18 ASA II, 52 ASA III, and 4 ASA IV patients. Mean total sedation dosing was fentanyl 3mcg/kg (2-10 mcg/kg) and midazolam 0.15 mg/kg (0.1-0.5 mg/kg). Per protocol, all patients received supplemental oxygen during the procedure with a majority of patients only requiring nasal cannula (63%). Five of the infants (6%) were electively intubated for PEG placement due to airway or other concerns. One procedure was aborted due to medical instability and was completed in the OR under GA. Feedings had returned to pre-PEG rates/volumes by a mean of 2.1 days (115 days). There were 2 significant complications; one case resulted in a perforated viscus, and a second patient had pneumoperitoneum with respiratory distress. There was no mortality due to the PEG placement. Conclusions: Sedated bedside PEG placement in chronically ill neonates can be an effective and safe method of providing permanent enteral access. There were few serious complications, especially given the chronic medical acuity of this population, and the outcomes data appears comparable with other reported series. We believe that careful patient assessment and selection along with utilization of a multidisciplinary team are keys to successful utilization of sedated PEG placement in this special and fragile population of infants.
Mo1964 Epidemiology of Constipation in Children and Adults Suzanne M. Mugie, Marc A. Benninga, Carlo Di Lorenzo Background and aims: Constipation is a common problem worldwide in children and adults, with a significant impact on quality of life, affecting both physical and emotional well-being. We reviewed the published literature on the epidemiology of constipation in the general pediatric and adult population without co-morbidities, in order to assess its geographic, gender and age distribution, and associated factors. Methods: A search of the Medline database was performed. Study selection criteria included: (1) studies of populationbased samples; (2) containing data on the prevalence of constipation without obvious organic etiology; (3) in pediatric, adult or elderly population; (4) published in English and full manuscript form. Fifty-eight studies met our inclusion criteria and 10 other articles were identified by reviewing the references of the relevant articles. Results: The prevalence of constipation in the worldwide general population ranged from 0.7% to 79% (median 16%) Nineteen articles investigated the prevalence of constipation in children with a range of 0.7%-29.6% (median 12%). Prevalence rates in North America were 3.2%-45% (median 16%), in Europe 0.7%-79% (median 19.2%), in Asia 1.4%-32.9% (median 10.8%), in Oceania 4.4%-30.7% (median 19.7%), in South America 26.8%-28% and a study from South Africa showed a prevalence rate of 29.2% in the elderly population. Because of different criteria used to define constipation and various ages investigated, no statistical comparison can be made between countries and/or continents. The majority of the reviewed studies reported a predominance of females in the prevalence of constipation with an overall F/M ratio of 1.5. Variance of gender prevalence of constipation in children was reported in 10 studies. There was a slight higher prevalence of constipation in girls compared to boys, with an F/M ratio of 1.2. Sixteen studies reported on the relationship between age and prevalence of constipation, with a majority suggesting an increase in prevalence with age. Subjects with lower income and lower level of education had significantly higher rates of constipation. An association between Black and Hispanic race and constipation has been suggested, but the data are conflicting. The relationship between excessive weight or obesity and constipation was reported in multiple studies and there was a trend towards increased prevalence of constipation in individuals with immobility or less self-reported physical activity. Conclusion: Constipation is a common problem worldwide in both adults and children with a very variable prevalence. Increased age, female sex, lower income and lower level of education are risk factors for the development of constipation.
Mo1962 Novel Characterization of Drug-Associated Pancreatitis in Children Harrison X. Bai, Michael Ma, Alexander Park, Sahibzada U. Latif, Vineet Bhandari, Sohail Z. Husain Introduction: Drugs are commonly associated with pancreatitis. However, little is known about the influence of drugs in children who present with acute pancreatitis. Thus, in this study, our aims were to understand the types of drugs associated with pancreatitis in children and to identify factors that distinguish cases with drug-associated pancreatitis from other etiologies. Methods: Upon institutional IRB approval, we obtained data on all children (ages 0 to 20 years) admitted to Yale-New Haven Children's Hospital with pancreatitis between 2004 and 2007. Medication-related pancreatitis etiology was assigned only if a patient was taking a medication listed in the AGA Technical Bulletin on Acute Pancreatitis as having a “definite,” “probable” or “possible” association with acute pancreatitis. Relevant clinical data were collected from patients' charts in those who met inclusion criteria. These included patient demographics, BMI percentile, weight-for-age percentile, clinical presentation, hospital management, and clinical course of pancreatitis. Statistical analysis was performed by comparing continuous variables using a Student t-test or Mann-Whitney U-test, whereas discrete variables were compared using chi-square analysis. Results: We found 55 episodes that were drug-associated, corresponding to 51 patients. The most common comorbidities
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Melan A was positive in the normal adrenal cortex and negative in the tumour cells. Of note, the patient's 9 year-old brother had no detectable adrenal masses on abdominal ultrasound. Adrenal tumours are more prevalent in patients with FAP compared to the general population. The median age at diagnosis is typically 40 - 50 years and there have been no reported cases of adrenal masses in FAP patients younger than 14 years. While the majority of these incidentally discovered lesions (incidentalomas) are benign, others include hypersecreting adenomas, pheochromocytomas, and adrenal adenocarcinomas. In this case, histological analysis of the mass was suggestive of an early endocrine tumour. Overall, there are few reports characterizing adrenal tumours in FAP patients with sequenced APC mutations. The genotype inherent in this family is known to cause severe polyposis and earlier onset disease. Given the age of our patient at diagnosis, it is possible that c.3927_ 3931delAAAGA mutations may also confer a susceptibility to early onset adrenal disease. Mo1967 Similarity and Discrepancy in Proliferative Activity and mRNA Expression Pattern of Proliferative Genes in Histologically Intact Children and Colorectal Cancer Samples Compared to Normal Colonic Epithelium From Healthy Adults Katalin Leiszter, Orsolya Galamb, Ferenc Sipos, Tibor Krenács, Sándor Spisák, Gábor Veres, András Kiss, Barnabas Wichmann, Kinga Tóth, Gabor Valcz, Árpád V. Patai, Alexandra Kalmar, Béla Molnár, Zsolt Tulassay
Median prevalence rate of constipation in the worldwide general pediatric and adult population per country
Background: The incidence and prevalence of colorectal cancer increase over the age of 40, while sporadic colorectal cancer is infrequent in childhood and in young adults. The imbalance of epithelial proliferation and apoptosis may result in age-related gastrointestinal alterations like sporadic colorectal cancer. Aims: Our aims were the determination and comparison of mitotic index (MI) in healthy samples from children and in colorectal adenoma-carcinoma sequence (ACS). Our further aim was the identification of proliferative genes which can be characterized by different expression in histologically intact children, adults and colorectal cancer samples. Materials and methods: 14 colonic biopsy from healthy children and 10 healthy adults, 10 colorectal adenomas and 10 colorectal cancers in adults were collected, fixed in formalin and embedded in paraffin. Proliferation was detected by Ki-67 immunohistochemistry, apoptosis by TUNEL method. After digital scanning of the slides MI was determined. 6 histologically intact children and 41 histologically intact adult colonic biopsy samples, 34 colorectal adenomas and 34 colorectal cancer samples were collected for the analysis of gene expression profile, using HGU133plus2.0 microarrays. SAM (Significant Analysis of Microarray) was performed for data analysis. Results: MI was significantly higher in histologically intact children colonic samples (0,34±0,07) compared to healthy adults (0,15±0,06) and adenomas (0,13±0,06) (p<0,05). The highest MI was found in tumors (0,42±0,10) and showed continuous increase with colorectal ACS. 16 proliferative genes with altered gene expression were determined during aging, 29 genes during colorectal carcinogenesis and 11 genes during both processes according to logFC and p-values. Conclusions: Proliferation increased in histologically intact children colonic samples compared to histologically intact adult colonic samples, but in contrast to colorectal cancer it can be a well-balanced regenerative process. Proliferative genes identified in the course of our study can play a crucial role in tumorigenesis and may help diagnosing sporadic colorectal cancer.
Mo1965 Genetic Evidence for Compound Heterozygotic Inheritance in 3 Siblings With Congenital Sucrase-Isomaltase Deficiency (CSID) Bruno P. Chumpitazi, Claudia C. Robayo-Torres, Bianca Haase, Tosso Leeb, Antone R. Opekun, Mark A. Gilger, Hassan Naim, Buford L. Nichols Sucrase-isomaltase (SI) is an enzyme complex with 2 activities, sucrase (SUC) and isomaltase (IM) that is expressed at the small intestine brush-border membrane, where it serves as a catalyst for the cleavage of sugar and starch. A 2006 report identified compound heterozygous mutations (CHM) at V577G (IM) and G1073D (SUC). Cellular studies have documented that V577G (IM) and G1073D (SUC) mutations inhibit exiting from the ER; the SUC mutation blocks its chaperone function for IM. Objective: Test the mode of inheritance in a family with CHM-CSID. Methods: Study of 3 siblings with CSID diagnosed by duodenal enzyme assays and 22 kindred by sucrose breath testing (SBT) and genomic SI sequencing. UL 13C-glucose and 13C-sucrose, (20mg, Isotec, Miamisburg, OH) were given orally. Breath samples were collected for 120 min. Breath 13CO2 enrichments were measured with a infrared spectrophotometer (POCone, Otsuka Electronics, Tokyo, Japan) and expressed as % coefficient of mean 30-90 min sucrose / glucose oxidation (CGO %). Controls were 16 kindred without mutations. DNA was isolated from blood using the Nucleon BACC2 kit (GE Healthcare, Freiburg, Germany) and all exons of SI were amplified by PCR and directly sequenced on an ABI 3730 capillary sequencer (Applied Biosystems, CA). Results: The 3 siblings, father and paternal grandmother had deficient digestion (< 98 CGO %) by SBT. Sequencing of SI revealed polymorphisms at V577G, G1073D, G1476A and I1523M. The G1073D allele was paternal and the remaining maternal polymorphisms. Conclusion: SBT phenotype correlated with sucrase activity and SI genotypes in this CHM-CSID family. The novel maternal mutations G1476A and I1523M of SUC appear to act as dominant negatives suppressing sucrose digestion in the youngest child lacking the familial V577G IM mutation. Characteristics of 3 Siblings with CSID
Mo1968 Risk of Lymphoma in Children With Inflammatory Bowel Disease Lori A. Ashworth, Corey A. Siegel, Paul D. Mitchell, Amy L. Billett, Athos Bousvaros BACKGROUND: Prior studies suggest an increased risk of lymphoma in adults with inflammatory bowel disease. Cases of lymphoma have also been reported in children with IBD. However, the precise risk of lymphoma in relation to drug exposure has not been ascertained in children. METHODS: We conducted a single center, retrospective study of 1560 children and young adults with IBD evaluated at Children's Hospital Boston between 1980 and 2008. Of this group, 184 patients were excluded due to incorrect diagnosis, one time second opinion visits, or missing hospital records. The remaining 1376 patients had charts reviewed to determine whether lymphoma developed while they were receiving their clinical care at our institution, and the duration of exposure to various IBD medications. The rate of lymphoma was calculated in patient-years of exposure for each class of medications utilized in inflammatory bowel disease. RESULTS: Of 1376 patients (706 male; age at diagnosis 12.1±4.0y; 766 CD, 528 UC, 48 IBD unclassified), we identified two patients who developed lymphoma (one Hodgkin, one anaplastic large cell), in 6,480 patient years of follow up (mean duration follow up 4.7 years per patient). Both patients were males (ages 12 and 18 years at time of lymphoma onset), and were receiving thiopurines but had not yet received biologics at the time of their cancer diagnosis. They were both treated with chemotherapy, and are alive without disease 32+ and 76+ months since diagnosis. The ratio of lymphoma to patient years of exposure for various medication classes is summarized in the table. We then estimated a risk of lymphoma in patients exposed to thiopurines by comparing our observed lymphoma incidence rate in patients exposed to thiopurines to the overall expected rate in the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database for Hodgkin and non-Hodgkin lymphoma in males and females ages 0-19 y. The absolute incidence rate of lymphoma for patients receiving thiopurines was 4.66 per 10,000 patient-years compared to the expected rate in SEER of 0.58 per 10,000 patient-years, with a standardized incidence ratio (SIR) of 7.78 (95% CI 0.77-43.45).CONCLUSION: The overall risk of lymphoma in children with IBD is low. However, this study suggests an increase in risk in the subset of children receiving thiopurines, comparable to that reported in studies of adults. While there may be an increased risk of lymphoma in children treated with thiopurines, the risk did not reach statistical significance in this large cohort. Lymphoma risk in children
Mo1966 Early Onset Adrenal Tumour in a Child With Familial Adenomatous Polyposis and APC Mutation at Codon 1309 Alfred K. Yeung, Josephine Ho, Cynthia Trevenen, Iwona T. Wrobel A 12 year-old boy of mixed First Nations heritage had presented to our service three years earlier because of a family history of familial adenomatous polyposis (FAP). He and his younger brother were subsequently diagnosed with the adenomatous polyposis coli (APC) gene mutation at codon 1309 (c.3927_3931delAAAGA) identified in his father and two paternal aunts. Screening colonoscopy at age 10 revealed two duodenal polyps and multiple tubular adenomas in the colon, prompting a prophylactic total proctocolectomy that year. At a routine follow-up, ultrasound examination for extracolonic manifestations of FAP revealed a mass in the right adrenal fossa. Computed tomography demonstrated a 4.8 cm heterogeneous mass with multiple calcifications. Initial endocrinological investigations for hormone hypersecretion revealed elevated urinary catecholamines. However, repeat testing was normal and the abnormal results were presumed to have been a laboratory reporting error. Plasma metanephrines, DHEAS, cortisol and ACTH following an overnight dexamethasone suppression test, aldosterone-renin ratio and electrolytes were unremarkable. Because of the raised risk of malignancy in adrenal masses greater than 4 cm in size and the presence of calcifications, an adrenalectomy was performed. Microscopy revealed an unencapsulated tumour with fragments of residual normal adrenal cortex intermingled with clusters of tumour cells. The tumour cells were arranged in small nests surrounded by S100-positive cells and separated by fibrovascular septae. No cytologic pleiomorphism or mitotic figures were seen. Extensive stromal fibrosis and marked adrenal medullary hyperplasia were noted. Immunostaining for Ki67 was minimal, and negative for synaptophysin and chromogranin.
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Impact of Obesity on Pediatric Cholecystectomy Nitin Gupta, Aliza B. Solomon, Edmund Kessler Background: The prevalence of cholecystectomies in children is on the rise. The impact of obesity on gallbladder disease and surgical outcomes in adults is well documented; however, there is minimal data in the pediatric population. Obesity appears to be a risk factor in pediatric gallbladder disease leading to a parallel increase in cholecystectomies. Methods: A retrospective chart review was performed on patients who underwent cholecystectomies between the years 2005-2010. Data collected included age, sex, height, weight, Body Mass Index (BMI) percentiles, past medical history, indications, prior imaging, length of stay, complications, comorbidities and type of surgery. Results: Preliminary results of 58 records were reviewed. The mean age of patients was 17.8 years (range 8-21) and 82.8% were female. There were 26 in the normal weight (NW) group and 32 in the overweight (OW) (BMI >85%) group. 55% of the surgeries were performed on the OW group. The mean number of cholecystectomies was 11 per year and there was no increased incidence of cholecystectomy across 5 years. The indication for cholecystectomy did not differ between the groups. The length of stay for acute surgery was longer amongst the NW group with 3.2 days (range 1-13) compared to 2.5 days (range 1-9) for the OW group. More patients in NW group had associated comorbidities that contributed to hospital stay such as sickle cell disease, renal disease and congenital heart defects. The mean operative time was 132.9 minutes (range 79-213) in the NW group and 154.8 minutes (range 96-249) in the OW group. Conclusion: Although many pediatric patients undergoing cholecystectomy are obese, obesity may not necessarily be directly linked with an increased prevalence of surgery. Obesity did impact the mean operative time and further studies are needed to examine this data for causal relationship.
Mo1963 Understanding Clostridium difficile-Associated Disease (CDAD) in Children at a Tertiary Care Children's Hospital: A 6 Year Retrospective Study Rodrigo Rodrigues, Khaled Bittar, Hossein Salimnia, Mohammad El-Baba Background: Although the incidence rate of CDAD has reportedly increased in the adult patient population, there is fewer data on this disease in children. Clostridium difficile (CD) has been seen traditionally seen as nonpathogenic in young infants, but recent data has shown increasing burden of CDAD among this age group. A retrospective study was performed to determine the pattern of C. difficile infection in our hospital and compare our results with previous studies in search of a better understanding of the clinical and epidemiological features of CDAD in children. Methods: We conducted a retrospective cohort study that includes patients who visited/ admitted to our hospital between January 1, 2004 and December 31, 2009. Patient records that documented an assay positive for CD toxin were extracted from a database maintained by the clinical virology laboratory and reviewed to obtain information on demographic characteristics, history of hospital visits, prior antibiotic use, patient location at the time of the beginning of symptoms and co-morbidities. CDAD was defined as clinical symptoms, such as diarrhea with or without blood, in a patient whose stool specimen tested positive for CD toxin. Results: We identified 203 patients with CDAD. Over the 6 years of the study, there was a linear increase in the number of patients diagnosed with CD infection from 25 cases in 2004 to 47 in 2009. There were 92 (45.3%) females and 111 (54.7%) males. Seventy percent were younger than 7 years and 40% were under 2 years of age. One hundred and sixty three patients (80%) had some chronic medical condition. Hematologic/oncologic conditions had the highest number of positive cases 62/ 203 (30%), followed by gastrointestinal, neuromuscular and cardiac patients. About two thirds of the patients developed symptoms during hospitalization for other medical condition. 146 patients (72%) had history of previous antibiotic use. Conclusions: Our data has shown increased frequency of CDAD in children. We also found that symptomatic CD infection is common in young children less than two years of age. This may be due to an increase in the number of tests ordered and a diffusion of the awareness of CD as an important cause of gastroenteritis in hospitalized patients. Patients with chronic medical conditions, specially, hematologic/oncologic and chronic gastrointestinal diseases deserve a special attention and a lower threshold for diagnosis and treatment.
Mo1961 Sedated Percutaneous Endoscopic Gastrostomy (PEG) Placement in the Neonate Alex Green, Edward G. Shepherd, Steven H. Erdman Background: Nutrition support is a cornerstone therapy for premature and sick neonates. Long-term nutrition support is best achieved by gastrostomy tube (GT) which can be placed endoscopically (PEG) using bedside sedation or operatively under general anesthesia (GA). Controversy exists regarding the safest method of PEG placement in ill neonates who may be at particular risk of respiratory or airway complications relating to GA. To avoid such complications, bedside PEG placement with IV sedation has been utilized in our neonatal intensive care units (NICUs). This multidisciplinary approach emphasizes individualized patient assessment and the presence of a neonatologist for sedation and airway management. Patients/Methods: Charts of all infants who underwent bedside PEG in our NICUs from August 2006 to March 2010 were reviewed. Available demographic information, past medical history, nutritional status at time of procedure and up to one year after, procedure information (ASA scores, medications, respiratory status), and short- and long-term outcomes were collected and analyzed. Results: A total of 93 patients underwent bedside PEG placement during the review period. The mean age at placement was 17.4 weeks (2-60 weeks) with an adjusted gestational age of 48.4 weeks (17-84 weeks). The average weight at the time of the procedure was 4298 gm (2175-8040 gm). The patients had a number of underlying conditions including bronchopulmonary dysplasia (45%), genetic disease (26%), intraventricular hemorrhage (22%), and poor weight gain (20%). There were 18 ASA II, 52 ASA III, and 4 ASA IV patients. Mean total sedation dosing was fentanyl 3mcg/kg (2-10 mcg/kg) and midazolam 0.15 mg/kg (0.1-0.5 mg/kg). Per protocol, all patients received supplemental oxygen during the procedure with a majority of patients only requiring nasal cannula (63%). Five of the infants (6%) were electively intubated for PEG placement due to airway or other concerns. One procedure was aborted due to medical instability and was completed in the OR under GA. Feedings had returned to pre-PEG rates/volumes by a mean of 2.1 days (115 days). There were 2 significant complications; one case resulted in a perforated viscus, and a second patient had pneumoperitoneum with respiratory distress. There was no mortality due to the PEG placement. Conclusions: Sedated bedside PEG placement in chronically ill neonates can be an effective and safe method of providing permanent enteral access. There were few serious complications, especially given the chronic medical acuity of this population, and the outcomes data appears comparable with other reported series. We believe that careful patient assessment and selection along with utilization of a multidisciplinary team are keys to successful utilization of sedated PEG placement in this special and fragile population of infants.
Mo1964 Epidemiology of Constipation in Children and Adults Suzanne M. Mugie, Marc A. Benninga, Carlo Di Lorenzo Background and aims: Constipation is a common problem worldwide in children and adults, with a significant impact on quality of life, affecting both physical and emotional well-being. We reviewed the published literature on the epidemiology of constipation in the general pediatric and adult population without co-morbidities, in order to assess its geographic, gender and age distribution, and associated factors. Methods: A search of the Medline database was performed. Study selection criteria included: (1) studies of populationbased samples; (2) containing data on the prevalence of constipation without obvious organic etiology; (3) in pediatric, adult or elderly population; (4) published in English and full manuscript form. Fifty-eight studies met our inclusion criteria and 10 other articles were identified by reviewing the references of the relevant articles. Results: The prevalence of constipation in the worldwide general population ranged from 0.7% to 79% (median 16%) Nineteen articles investigated the prevalence of constipation in children with a range of 0.7%-29.6% (median 12%). Prevalence rates in North America were 3.2%-45% (median 16%), in Europe 0.7%-79% (median 19.2%), in Asia 1.4%-32.9% (median 10.8%), in Oceania 4.4%-30.7% (median 19.7%), in South America 26.8%-28% and a study from South Africa showed a prevalence rate of 29.2% in the elderly population. Because of different criteria used to define constipation and various ages investigated, no statistical comparison can be made between countries and/or continents. The majority of the reviewed studies reported a predominance of females in the prevalence of constipation with an overall F/M ratio of 1.5. Variance of gender prevalence of constipation in children was reported in 10 studies. There was a slight higher prevalence of constipation in girls compared to boys, with an F/M ratio of 1.2. Sixteen studies reported on the relationship between age and prevalence of constipation, with a majority suggesting an increase in prevalence with age. Subjects with lower income and lower level of education had significantly higher rates of constipation. An association between Black and Hispanic race and constipation has been suggested, but the data are conflicting. The relationship between excessive weight or obesity and constipation was reported in multiple studies and there was a trend towards increased prevalence of constipation in individuals with immobility or less self-reported physical activity. Conclusion: Constipation is a common problem worldwide in both adults and children with a very variable prevalence. Increased age, female sex, lower income and lower level of education are risk factors for the development of constipation.
Mo1962 Novel Characterization of Drug-Associated Pancreatitis in Children Harrison X. Bai, Michael Ma, Alexander Park, Sahibzada U. Latif, Vineet Bhandari, Sohail Z. Husain Introduction: Drugs are commonly associated with pancreatitis. However, little is known about the influence of drugs in children who present with acute pancreatitis. Thus, in this study, our aims were to understand the types of drugs associated with pancreatitis in children and to identify factors that distinguish cases with drug-associated pancreatitis from other etiologies. Methods: Upon institutional IRB approval, we obtained data on all children (ages 0 to 20 years) admitted to Yale-New Haven Children's Hospital with pancreatitis between 2004 and 2007. Medication-related pancreatitis etiology was assigned only if a patient was taking a medication listed in the AGA Technical Bulletin on Acute Pancreatitis as having a “definite,” “probable” or “possible” association with acute pancreatitis. Relevant clinical data were collected from patients' charts in those who met inclusion criteria. These included patient demographics, BMI percentile, weight-for-age percentile, clinical presentation, hospital management, and clinical course of pancreatitis. Statistical analysis was performed by comparing continuous variables using a Student t-test or Mann-Whitney U-test, whereas discrete variables were compared using chi-square analysis. Results: We found 55 episodes that were drug-associated, corresponding to 51 patients. The most common comorbidities
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Melan A was positive in the normal adrenal cortex and negative in the tumour cells. Of note, the patient's 9 year-old brother had no detectable adrenal masses on abdominal ultrasound. Adrenal tumours are more prevalent in patients with FAP compared to the general population. The median age at diagnosis is typically 40 - 50 years and there have been no reported cases of adrenal masses in FAP patients younger than 14 years. While the majority of these incidentally discovered lesions (incidentalomas) are benign, others include hypersecreting adenomas, pheochromocytomas, and adrenal adenocarcinomas. In this case, histological analysis of the mass was suggestive of an early endocrine tumour. Overall, there are few reports characterizing adrenal tumours in FAP patients with sequenced APC mutations. The genotype inherent in this family is known to cause severe polyposis and earlier onset disease. Given the age of our patient at diagnosis, it is possible that c.3927_ 3931delAAAGA mutations may also confer a susceptibility to early onset adrenal disease. Mo1967 Similarity and Discrepancy in Proliferative Activity and mRNA Expression Pattern of Proliferative Genes in Histologically Intact Children and Colorectal Cancer Samples Compared to Normal Colonic Epithelium From Healthy Adults Katalin Leiszter, Orsolya Galamb, Ferenc Sipos, Tibor Krenács, Sándor Spisák, Gábor Veres, András Kiss, Barnabas Wichmann, Kinga Tóth, Gabor Valcz, Árpád V. Patai, Alexandra Kalmar, Béla Molnár, Zsolt Tulassay
Median prevalence rate of constipation in the worldwide general pediatric and adult population per country
Background: The incidence and prevalence of colorectal cancer increase over the age of 40, while sporadic colorectal cancer is infrequent in childhood and in young adults. The imbalance of epithelial proliferation and apoptosis may result in age-related gastrointestinal alterations like sporadic colorectal cancer. Aims: Our aims were the determination and comparison of mitotic index (MI) in healthy samples from children and in colorectal adenoma-carcinoma sequence (ACS). Our further aim was the identification of proliferative genes which can be characterized by different expression in histologically intact children, adults and colorectal cancer samples. Materials and methods: 14 colonic biopsy from healthy children and 10 healthy adults, 10 colorectal adenomas and 10 colorectal cancers in adults were collected, fixed in formalin and embedded in paraffin. Proliferation was detected by Ki-67 immunohistochemistry, apoptosis by TUNEL method. After digital scanning of the slides MI was determined. 6 histologically intact children and 41 histologically intact adult colonic biopsy samples, 34 colorectal adenomas and 34 colorectal cancer samples were collected for the analysis of gene expression profile, using HGU133plus2.0 microarrays. SAM (Significant Analysis of Microarray) was performed for data analysis. Results: MI was significantly higher in histologically intact children colonic samples (0,34±0,07) compared to healthy adults (0,15±0,06) and adenomas (0,13±0,06) (p<0,05). The highest MI was found in tumors (0,42±0,10) and showed continuous increase with colorectal ACS. 16 proliferative genes with altered gene expression were determined during aging, 29 genes during colorectal carcinogenesis and 11 genes during both processes according to logFC and p-values. Conclusions: Proliferation increased in histologically intact children colonic samples compared to histologically intact adult colonic samples, but in contrast to colorectal cancer it can be a well-balanced regenerative process. Proliferative genes identified in the course of our study can play a crucial role in tumorigenesis and may help diagnosing sporadic colorectal cancer.
Mo1965 Genetic Evidence for Compound Heterozygotic Inheritance in 3 Siblings With Congenital Sucrase-Isomaltase Deficiency (CSID) Bruno P. Chumpitazi, Claudia C. Robayo-Torres, Bianca Haase, Tosso Leeb, Antone R. Opekun, Mark A. Gilger, Hassan Naim, Buford L. Nichols Sucrase-isomaltase (SI) is an enzyme complex with 2 activities, sucrase (SUC) and isomaltase (IM) that is expressed at the small intestine brush-border membrane, where it serves as a catalyst for the cleavage of sugar and starch. A 2006 report identified compound heterozygous mutations (CHM) at V577G (IM) and G1073D (SUC). Cellular studies have documented that V577G (IM) and G1073D (SUC) mutations inhibit exiting from the ER; the SUC mutation blocks its chaperone function for IM. Objective: Test the mode of inheritance in a family with CHM-CSID. Methods: Study of 3 siblings with CSID diagnosed by duodenal enzyme assays and 22 kindred by sucrose breath testing (SBT) and genomic SI sequencing. UL 13C-glucose and 13C-sucrose, (20mg, Isotec, Miamisburg, OH) were given orally. Breath samples were collected for 120 min. Breath 13CO2 enrichments were measured with a infrared spectrophotometer (POCone, Otsuka Electronics, Tokyo, Japan) and expressed as % coefficient of mean 30-90 min sucrose / glucose oxidation (CGO %). Controls were 16 kindred without mutations. DNA was isolated from blood using the Nucleon BACC2 kit (GE Healthcare, Freiburg, Germany) and all exons of SI were amplified by PCR and directly sequenced on an ABI 3730 capillary sequencer (Applied Biosystems, CA). Results: The 3 siblings, father and paternal grandmother had deficient digestion (< 98 CGO %) by SBT. Sequencing of SI revealed polymorphisms at V577G, G1073D, G1476A and I1523M. The G1073D allele was paternal and the remaining maternal polymorphisms. Conclusion: SBT phenotype correlated with sucrase activity and SI genotypes in this CHM-CSID family. The novel maternal mutations G1476A and I1523M of SUC appear to act as dominant negatives suppressing sucrose digestion in the youngest child lacking the familial V577G IM mutation. Characteristics of 3 Siblings with CSID
Mo1968 Risk of Lymphoma in Children With Inflammatory Bowel Disease Lori A. Ashworth, Corey A. Siegel, Paul D. Mitchell, Amy L. Billett, Athos Bousvaros BACKGROUND: Prior studies suggest an increased risk of lymphoma in adults with inflammatory bowel disease. Cases of lymphoma have also been reported in children with IBD. However, the precise risk of lymphoma in relation to drug exposure has not been ascertained in children. METHODS: We conducted a single center, retrospective study of 1560 children and young adults with IBD evaluated at Children's Hospital Boston between 1980 and 2008. Of this group, 184 patients were excluded due to incorrect diagnosis, one time second opinion visits, or missing hospital records. The remaining 1376 patients had charts reviewed to determine whether lymphoma developed while they were receiving their clinical care at our institution, and the duration of exposure to various IBD medications. The rate of lymphoma was calculated in patient-years of exposure for each class of medications utilized in inflammatory bowel disease. RESULTS: Of 1376 patients (706 male; age at diagnosis 12.1±4.0y; 766 CD, 528 UC, 48 IBD unclassified), we identified two patients who developed lymphoma (one Hodgkin, one anaplastic large cell), in 6,480 patient years of follow up (mean duration follow up 4.7 years per patient). Both patients were males (ages 12 and 18 years at time of lymphoma onset), and were receiving thiopurines but had not yet received biologics at the time of their cancer diagnosis. They were both treated with chemotherapy, and are alive without disease 32+ and 76+ months since diagnosis. The ratio of lymphoma to patient years of exposure for various medication classes is summarized in the table. We then estimated a risk of lymphoma in patients exposed to thiopurines by comparing our observed lymphoma incidence rate in patients exposed to thiopurines to the overall expected rate in the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database for Hodgkin and non-Hodgkin lymphoma in males and females ages 0-19 y. The absolute incidence rate of lymphoma for patients receiving thiopurines was 4.66 per 10,000 patient-years compared to the expected rate in SEER of 0.58 per 10,000 patient-years, with a standardized incidence ratio (SIR) of 7.78 (95% CI 0.77-43.45).CONCLUSION: The overall risk of lymphoma in children with IBD is low. However, this study suggests an increase in risk in the subset of children receiving thiopurines, comparable to that reported in studies of adults. While there may be an increased risk of lymphoma in children treated with thiopurines, the risk did not reach statistical significance in this large cohort. Lymphoma risk in children
Mo1966 Early Onset Adrenal Tumour in a Child With Familial Adenomatous Polyposis and APC Mutation at Codon 1309 Alfred K. Yeung, Josephine Ho, Cynthia Trevenen, Iwona T. Wrobel A 12 year-old boy of mixed First Nations heritage had presented to our service three years earlier because of a family history of familial adenomatous polyposis (FAP). He and his younger brother were subsequently diagnosed with the adenomatous polyposis coli (APC) gene mutation at codon 1309 (c.3927_3931delAAAGA) identified in his father and two paternal aunts. Screening colonoscopy at age 10 revealed two duodenal polyps and multiple tubular adenomas in the colon, prompting a prophylactic total proctocolectomy that year. At a routine follow-up, ultrasound examination for extracolonic manifestations of FAP revealed a mass in the right adrenal fossa. Computed tomography demonstrated a 4.8 cm heterogeneous mass with multiple calcifications. Initial endocrinological investigations for hormone hypersecretion revealed elevated urinary catecholamines. However, repeat testing was normal and the abnormal results were presumed to have been a laboratory reporting error. Plasma metanephrines, DHEAS, cortisol and ACTH following an overnight dexamethasone suppression test, aldosterone-renin ratio and electrolytes were unremarkable. Because of the raised risk of malignancy in adrenal masses greater than 4 cm in size and the presence of calcifications, an adrenalectomy was performed. Microscopy revealed an unencapsulated tumour with fragments of residual normal adrenal cortex intermingled with clusters of tumour cells. The tumour cells were arranged in small nests surrounded by S100-positive cells and separated by fibrovascular septae. No cytologic pleiomorphism or mitotic figures were seen. Extensive stromal fibrosis and marked adrenal medullary hyperplasia were noted. Immunostaining for Ki67 was minimal, and negative for synaptophysin and chromogranin.
AGA Abstracts
S-688