Impact of villitis of unknown etiology and adverse acute neonatal outcomes in Eastern Ontario.

INTRODUCTION: Villitis of unknown etiology (VUE) is a histopathological lesion associated with adverse neonatal outcomes. We seek to define the obscure relationship between the severity and distribution of VUE and adverse neonatal outcomes. METHODS: A retrospective chart review was conducted of pathologic findings from singleton placentas diagnosed with VUE between 2013 and 2019. Control placentas were matched 1:1 for gestational age and presence/absence of fetal IUGR. Neonatal outcomes of interest included: newborn resuscitation, NICU admission, Apgar scores and cord blood acidosis. Odds ratio and 95 % confidence intervals were calculated with controls as the reference. RESULTS: 452 placentas were included. 35 % of pregnancies were complicated by IUGR. When analyzed by severity (low-grade: OR = 4.75 [2.86-8.14]; high-grade: OR = 4.76 [2.71-8.79]) and distribution (focal: OR = 5.24 [2.87-10.17]; multifocal: OR = 4.90 [2.90-8.59]), VUE was significantly associated with need for newborn resuscitation. No other neonatal outcomes of interest were significantly associated with VUE diagnosis. DISCUSSION: We determined a statistically significant association between VUE severity and distribution and the need for newborn resuscitation. VUE lesions were not associated with any additional neonatal outcomes of interest. Further studies with larger sample sizes are required to confirm these associations for obstetric and neonatal case management.

Establishing normal ranges for fetal and neonatal small and large intestinal lengths: results from a prospective postmortem study.

Objective: To establish reference intervals (RIs) for fetal and neonatal small and large intestinal lengths. Methods: Linear measurements on small and large intestines were made upon postmortem examination of 131 preterm and term infants with gestational ages between 13 and 41 weeks. All cases were referred from the Eastern Ontario and Western Québec regions to a tertiary care hospital. Age and sex partitions were considered and RI limits were estimated. Results: Data consisted of 72 male (54.96%) and 59 female (45.04%) fetuses and neonates with mean gestational age of 25.6 weeks. Results showed that small and large intestinal lengths increased linearly with gestational age. RIs for small intestinal length (cm) of fetuses and neonates aged 13-20 weeks were (21.1, 122.4); of those aged 21-28 weeks were (57.7, 203.8); of those aged 29-36 weeks were (83.6, 337.1); and of those aged 37-41 weeks were (132.8, 406.4). RIs for large intestinal length (cm) of fetuses and neonates from the same four age groups were (5.1, 21.4), (12.7, 39.7), (32.4, 62.4), and (29.1, 82.2). Conclusions: Establishing accurate RIs for premature and term infants has clinical relevance for pathologists performing postmortem analysis and for surgeons planning postoperative management of patients. The results of this study reaffirm that fetal small and large intestinal lengths increase linearly with gestational age irrespective of sex. Future studies should aim to further investigate the role of possible confounders on growth of fetal intestinal length, including maternal factors such as age and substance use during pregnancy.

Peri-Operative Liver Fibrosis and Native Liver Survival in Pediatric Patients with Biliary Atresia: A Systematic Review and Meta-Analysis.

No systematic review to date has examined histopathological parameters in relation to native liver survival in children who undergo the Kasai operation for biliary atresia (BA). A systematic review and meta-analysis is presented, comparing the frequency of native liver survival in peri-operative severe vs. non-severe liver fibrosis cases, in addition to other reported histopathology parameters. Records were sourced from MEDLINE, Embase, and CENTRAL databases. Studies followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and compared native liver survival frequencies in pediatric patients with evidence of severe vs. non-severe liver fibrosis, bile duct proliferation, cholestasis, lobular inflammation, portal inflammation, and giant cell transformation on peri-operative biopsies. The primary outcome was the frequency of native liver survival. A random effects meta-analysis was used. Twenty-eight observational studies were included, 1,171 pediatric patients with BA of whom 631 survived with their native liver. Lower odds of native liver survival in the severe liver fibrosis vs. non-severe liver fibrosis groups were reported (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.08-0.33; I2 =46%). No difference in the odds of native liver survival in the severe bile duct destruction vs. non-severe bile duct destruction groups were reported (OR, 0.17; 95% CI, 0.00-63.63; I2 =96%). Lower odds of native liver survival were documented in the severe cholestasis vs. non-severe cholestasis (OR, 0.10; 95% CI, 0.01-0.73; I2 =80%) and severe lobular inflammation vs. non-severe lobular inflammation groups (OR, 0.02; 95% CI, 0.00-0.62; I2 =69%). There was no difference in the odds of native liver survival in the severe portal inflammation vs. non-severe portal inflammation groups (OR, 0.03; 95% CI, 0.00-3.22; I2 =86%) or between the severe giant cell transformation vs. non-severe giant cell transformation groups (OR, 0.15; 95% CI, 0.00-175.21; I2 =94%). The meta-analysis loosely suggests that the presence of severe liver fibrosis, cholestasis, and lobular inflammation are associated with lower odds of native liver survival in pediatric patients after Kasai.

Diverticular disease in a pediatric patient with Crohn's disease mimicking a perforated post-appendectomy appendiceal stump.

We present the finding of a diverticulum in the colonic wall of the cecum, arising in the context of ileocecal stricture in a child with Crohn disease mimicking a post-appendectomy perforated appendiceal stump. To our knowledge, a non-Meckel diverticulum in a pediatric patient with Crohn disease has not yet been reported and we examine the mechanics behind it. According to the Laplace Law, the pressure inside a container with curved walls is inversely proportional to its radius. A diverticulum forms at the point of maximum stricture and at the locus of least resistance (weakness) in the bowel wall due to the inflammatory bowel disease. The long-time interval between diagnosis of ileocecal stricture and surgery (9 months) is important to allow the formation of this diverticulum. Continued follow-up in adulthood is warranted due to an increased risk of intestinal diverticular disease and neoplasms in patients with Crohn disease.

Evaluating the Prognostic Implication of the Collins Histology Scoring System in a Pediatric Eastern Ontario Population With Eosinophilic Esophagitis.

INTRODUCTION: Collins et al developed a histology scoring system (EoE HSS) to assess multiple pathologic features. The aim of this study is to identify if the EoE HSS can better detect endoscopic and symptom improvement vs the Peak Eosinophilic Count (PEC). METHODS: A retrospective chart review was performed for patients during 2014-2016. All patients ≤18 years old with a diagnosis of EoE and whose records included initial and follow-up upper gastrointestinal endoscopies were included. Severity and extent of endoscopic features were scored using 8 parameters, from normal to maximum change for each location of the esophageal biopsy. RESULTS: Forty patients with EoE were included in the study, of which 35 (87.5%) patients demonstrated symptom and 25 (62.5%) endoscopic improvement at the time of follow-up. In the proximal esophagus, the EoE HSS outperformed the change in eosinophil count of the Children's Hospital of Eastern Ontario (CHEO) practice in predicting endoscopic improvement by 16.8% when examining the change in grade and 17.1% when examining the change in stage scores. CONCLUSIONS: At our institution, adoption of the EoE HSS in assessing biopsies of EoE patients might be warranted, compared to the traditional practice. However, a bigger sample size may give a more robust difference in all locations.

Associations between Cellular Energy and Pediatric Inflammatory Bowel Disease Patient Response to Treatment.

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are chronic diseases of the gastrointestinal tract, with an unknown etiology, that affect over 6.8 million people worldwide. To characterize disease pathogenesis, proteomic and bioinformatic analyses were performed on colon biopsies collected during diagnostic endoscopy from 119 treatment-naïve pediatric patients, including from 78 IBD patients and 41 non-IBD patients who served as controls. Due to the presence of noninflamed and/or inflamed regions in IBD patients, up to two biopsies were obtained from IBD patients as compared to a single noninflamed biopsy from non-IBD pediatric control patients. Additional biopsies were obtained and analyzed from 33 of the IBD patients after IBD-directed therapeutic intervention for comparison of pre- and post-treatment proteomes. SuperSILAC was utilized to perform quantitative analysis of homogenized tissues, which were processed by filter-aided sample preparation. Hierarchical clustering and principal component analyses revealed proteomic patterns that distinguished inflamed from noninflamed tissues independent of therapy. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of pre- and post-treatment proteomes from CD patients identified over 100 proteins that are significantly different between patients who responded and those who did not respond to therapy, including creatine kinase B and basigin.

Homozygous WNT9B variants in two families with bilateral renal agenesis/hypoplasia/dysplasia.

WNT9B plays a key role in the development of the mammalian urogenital system. It is essential for the induction of mesonephric and metanephric tubules, the regulation of renal tubule morphogenesis, and the regulation of renal progenitor cell expansion and differentiation. To our knowledge, WNT9B has not been associated with renal defects in humans; however, WNT9B-/- mice have renal agenesis/hypoplasia and reproductive tract abnormalities. We report four individuals from two unrelated consanguineous families with bilateral renal agenesis/hypoplasia/dysplasia and homozygous variants in WNT9B. The proband from Family 1 has bilateral renal cystic dysplasia and chronic kidney disease. He has two deceased siblings who presented with bilateral renal hypoplasia/agenesis. The three affected family members were homozygous for a missense variant in WNT9B (NM_003396.2: c.949G>A/p.(Gly317Arg)). The proband from Family 2 has renal hypoplasia/dysplasia, chronic kidney disease, and is homozygous for a nonsense variant in WNT9B (NM_003396.2: c.11dupC/p.(Pro5Alafs*52)). Two of her siblings died in the neonatal period, one confirmed to be in the context of oligohydramnios. The proband's unaffected brother is also homozygous for the nonsense variant in WNT9B, suggesting nonpenetrance. We propose a novel association of WNT9B and renal anomalies in humans. Further study is needed to delineate the contribution of WNT9B to genitourinary anomalies in humans.

Impact of SARS-CoV-2 on the clinical outcomes and placental pathology of pregnant women and their infants: A systematic review.

Pregnant women are susceptible to viral infections due to physiological changes such as cell-mediated immunity. No severe adverse pregnancy or neonatal outcomes have been consistently reported in 2019 novel coronavirus disease (COVID-19) positive pregnancy cases. There are controversies around the role of COVID-19 in pregnancy. A systematic review was conducted to examine clinical maternal and neonatal clinical outcomes. Studies were included if they reported SARS-CoV-2 infection among pregnant women and/or COVID-19 positive neonates as validated by positive antibody testing or viral testing using polymerase chain reaction. Case series, case reports, case-control studies, and comparative studies were included. Eight hundred and thirty-seven records were identified, resulting in 525 records for level I screening. Forty-one were included after full-text review. Results suggest elevated rates of intensive care unit (ICU) admission, gestational diabetes, preeclampsia, C-sections, pre-term birth, and C-reactive protein (CRP) in comparison to pregnant women without SARS-CoV-2. Careful monitoring of pregnancies with SARS-CoV-2 is recommended.

Risk of Lower Birth Weight and Shorter Gestation in Oocyte Donation Pregnancies Compared With Other Assisted Reproductive Technology Methods: Systematic Review.

OBJECTIVE: Oocyte donation (OD) is associated with an increased risk of pregnancy-induced hypertension, but the evidence of an association between OD and infant outcomes, including birth weight and gestational age, is conflicting. This study sought to determine the associations between oocyte donation and birth weight or gestational age compared with other forms of autologous oocyte assisted reproductive technology (ART). METHODS: Medline, Embase, and the CENTRAL Trials Registry of the Cochrane Collaboration were searched using a comprehensive search strategy. Studies of women over 24 weeks gestation compared infant outcomes among OD pregnancies versus other ART. Study quality was assessed, and a meta-analysis of mean birth weight and gestational age was conducted using a random effects model. RESULTS: Nineteen studies were included. Four studies showed a significant association between OD and lower birth weights, and five studies found significant differences in gestational age between OD and autologous oocyte ART. The pooled difference in birth weight means between OD and autologous ART was -42 (-88, 4) . The pooled difference in gestational age was -0.4 weeks (-0.8, 0.0 weeks). CONCLUSION: A high degree of interstudy heterogeneity exists, and the association between OD and infant outcomes remains unclear.

Viable versus nonviable positive margins in Ewing sarcoma and associated recurrence rates: A systematic review.

Residual tumor after curative intent therapy in patients with Ewing's sarcoma is of great clinical significance. Surgeons use the resection margin to indicate the completeness of a surgical excision. However, this margin may be either nonviable/necrotic or viable. This systematic review examines the 5-year event-free survival rate and local recurrence as a function of positive resection margins that are nonviable/necrotic versus those that are viable. Multiple databases were searched using the Ovid interface. After full text screening, 45 articles that reported either margin or postchemotherapy histology and one or more outcomes of interest were identified, and two articles reported on margin and histology simultaneously. An attempt was made to contact the remaining authors and one author was able to provide additional data. The data from the three studies suggest that prognosis in ES depends on both margin involvement and the postchemotherapy histological response simultaneously. However, radiation therapy likely improves local control in patients with inadequate surgical margins, regardless of histological response. This is an area where there is a paucity of evidence that needs to be rectified to ensure that ES patients are provided the highest quality of evidence-based care.

Sclerosing Pneumocytoma of the Lungs Arising in a Child With PTEN Mutation.

We report a rare case of sclerosing pneumocytoma occurring in a child with PTEN mutation. A 13-year-old female presented to the emergency department of an adult hospital following 2 to 3 days of upper respiratory tract infection symptoms. A primary lung lesion was discovered during her initial chest X-ray to rule out pneumonia. The patient underwent an uneventful thoracoscopic right upper lobe segmentectomy. The pathology demonstrated a sclerosing pneumocytoma of the lung. She tested positive for PTEN hamartoma tumor syndrome with a pathogenic variant at c.388 C > T. The PTEN mutation was also identified in the sclerosing pneumocytoma. Further study of PTEN mutation in sclerosing pneumocytoma is warranted.

Dermal non-neural granular cell tumor in a 3-year-old child.

Dermal non-neural granular cell tumors, also known as primitive polypoid granular cell tumors, are a rare group of distinct cutaneous non-neural granular cell tumors. Pediatric cases are rare, and to the best of our knowledge, we report the youngest patient with dermal non-neural granular cell tumors.

Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm: A Systematic Literature Review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive hematologic malignancy characterized by frequent skin involvement that most commonly affects older patients. BPDCN is known to have a poor prognosis. Our objective was to assess if outcome and disease prognosis were independently influenced by age when evaluated with clinical presentation, sex, and treatment regimens. We conducted a systematic review to identify BPDCN cases, to compare pediatric BPDCN cases with adult cases. A total of 125 publications were identified detailing 356 cases. Including 1 pediatric case from our institution, 74 were children, and 283 were adults aged 19 or over. Age was shown to be an independent prognostic factor predictive of more favorable outcomes across measures including initial response to therapy, likelihood of relapse, and overall survival at follow-up. The distribution of affected organs at diagnosis was similar across children and adults and type of clinical presentation did not disproportionately influence 1 age group's prognosis over the other. Acute lymphoblastic leukemia-type chemotherapy regimens were shown to be superior to other chemotherapy regimens (acute myeloid leukemia, lymphoma, acute lymphoblastic leukemia/lymphoma, other, or none) in inducing complete remission. Allogeneic stem cell transplantation was shown to increase mean survival time. Future research may be directed toward elucidating the further morphologic, cytogenetic, and cytochemical differences between younger and older BPDCN patients.

Validation of an algorithm to identify children with biopsy-proven celiac disease from within health administrative data: An assessment of health services utilization patterns in Ontario, Canada.

IMPORTANCE: Celiac disease (CD) is a common pediatric illness, and awareness of gluten-related disorders including CD is growing. Health administrative data represents a unique opportunity to conduct population-based surveillance of this chronic condition and assess the impact of caring for children with CD on the health system. OBJECTIVE: The objective of the study was to validate an algorithm based on health administrative data diagnostic codes to accurately identify children with biopsy-proven CD. We also evaluated trends over time in the use of health services related to CD by children in Ontario, Canada. STUDY DESIGN AND SETTING: We conducted a retrospective cohort study and validation study of population-based health administrative data in Ontario, Canada. All cases of biopsy-proven CD diagnosed 2005-2011 in Ottawa were identified through chart review from a large pediatric health care center, and linked to the Ontario health administrative data to serve as positive reference standard. All other children living within Ottawa served as the negative reference standard. Case-identifying algorithms based on outpatient physician visits with associated ICD-9 code for CD plus endoscopy billing code were constructed and tested. Sensitivity, specificity, PPV and NPV were tested for each algorithm (with 95% CI). Poisson regression, adjusting for sex and age at diagnosis, was used to explore the trend in outpatient visits associated with a CD diagnostic code from 1995-2011. RESULTS: The best algorithm to identify CD consisted of an endoscopy billing claim follow by 1 or more adult or pediatric gastroenterologist encounters after the endoscopic procedure. The sensitivity, specificity, PPV, and NPV for the algorithm were: 70.4% (95% CI 61.1-78.4%), >99.9% (95% CI >99.9->99.9%), 53.3% (95% CI 45.1-61.4%) and >99.9% (95% CI >99.9->99.9%) respectively. It identified 1289 suspected CD cases from Ontario-wide administrative data. There was a 9% annual increase in the use of this combination of CD-associated diagnostic codes in physician billing data (RR 1.09, 95% CI 1.07-1.10, P<0.001). CONCLUSIONS: With its current structure and variables Ontario health administrative data is not suitable in identifying incident pediatric CD cases. The tested algorithms suffer from poor sensitivity and/or poor PPV, which increase the risk of case misclassification that could lead to biased estimation of CD incidence rate. This study reinforced the importance of validating the codes used to identify cohorts or outcomes when conducting research using health administrative data.

Value of upper endoscopic biopsies in predicting medical refractoriness in pediatric patients with ulcerative colitis.

Refractory ulcerative colitis (UC) occurs in patients who experience a severe disease manifestation that is unresponsive to medical therapy. The assessment of upper endoscopic microscopic findings and its correlation with refractory UC has not been fully studied in pediatric patients and is the focus of this study. Medical records of UC patients treated at a tertiary pediatric center between 2000 and 2014 were reviewed. Endoscopic biopsies of the upper gastrointestinal (GI) tract of patients meeting a priori inclusion criteria were compared between refractory UC patients and nonrefractory UC patients for active inflammation. Statistically significant differences were determined between groups, and tissues shown to have significant differences were further evaluated for their diagnostic performance. A total of 52 patients were included, 26 in each group. Significant differences were observed in intraepithelial neutrophil infiltration and percentage involvement of crypts/glands for the antrum, body, and duodenal bulb (P ≤ .001, .005, and .01 [intraepithelial neutrophil infiltration] and P = .001, .009, and .015 [% involvement], respectively). Microabscesses of mucosal glands/crypts were also experienced in a greater number of refractory UC patients in the stomach (ie, antrum and/or body of stomach; P = .005) and duodenum (ie, duodenum and/or duodenal bulb; P = .023). The sensitivity and specificity of upper GI tissues to predict refractory UC were moderate, with sensitivities ranging from 38% to 67% and specificities ranging from 81% to 100%. Our results suggest that children with refractory UC are more likely to have active inflammation in the upper GI tract, and thus, this may represent a predictor of responsiveness to current medical therapy.

Review of Current Applications of Immunohistochemistry in Pediatric Nonneoplastic Gastrointestinal, Hepatobiliary, and Pancreatic Lesions.

Immunohistochemical (IHC) stains are widely used by pathologists for a variety of considerations in the diagnostic workup of pediatric nonneoplastic lesions in gastrointestinal (GI), hepatic, biliary, and pancreatic lesions. The pathologic changes cover a wide range and types of presentations, including inflammatory (bacterial and viral), metaplastic, posttransplant lymphoproliferative, autoimmune, metabolic, degenerative, developmental, and genetic conditions, among others. The everyday practical value of IHC stains covers primary identification, confirmation, differential, and/or exclusionary roles in the hands and eyes and minds of the practitioners. This article is intended to review and discuss the currently available IHC stains for a variety of pediatric GI, hepatobiliary, and pancreatic lesions as encountered in the day-to-day practice of pathologists and clinicians. It reflects the most recent methods and types of IHC stains with the stated aim of helping to provide a quick reference for diagnostic considerations and thereby facilitate the workup of a broad range of GI and related conditions in a pediatric population. The tables provide a handy reference on a wide range of IHC stains for commonly encountered lesions covering a variety of pediatric GI, hepatobiliary, and pancreatic conditions that are amenable to light microscopic diagnostic interpretation.

Update on molecular findings in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour in children and adolescents. Histologically RMS resembles developing fetal striated skeletal muscle. RMS is stratified into different histological subtypes which appear to influence management plans and patient outcome. Importantly, molecular classification of RMS seems to more accurately capture the true biology and clinical course and prognosis of RMS to guide therapeutic decisions. The identification of PAX-FOXO1 fusion status in RMS is one of the most important updates in the risk stratification of RMS. There are several genes close to PAX that are frequently altered including the RAS family, FGFR4, PIK3CA, CTNNB1, FBXW7, and BCOR. As with most paediatric blue round cell tumours and sarcomas, chemotherapy is the key regimen for RMS therapy. Currently there are no direct inhibitors against PAX-FOXO1 fusion oncoproteins and targeting epigenetic cofactors is limited to clinical trials. Failure of therapy in RMS is usually related to drug resistance and metastatic disease. Through this review we have highlighted most of the molecular aspects in RMS and have attempted to correlate with RMS classification, treatment and prognosis.

Value of histopathology for predicting the post-operative complications of ileo-anal anastomosis (J-pouch) procedure in children with refractory ulcerative colitis.

The J-pouch is a surgical procedure offered to children with refractory ulcerative colitis (UC) who have undergone subtotal colectomy to reconstruct a reservoir function with ileo-anal anastomosis. Unfortunately, post-operative complications may occur and can compromise the pouch function. We assessed rectal histopathology to determine whether severity of inflammation in the rectum prior to the creation of the J-Pouch was associated with post-operative complications. We retrospectively reviewed the histopathology of all J-pouch procedure specimens from paediatric patients during the period 2000-2013 using an objective grading system that assesses the chronicity and activity of the UC disease. We analysed the parameters for association with the post-operative complications. A classification tree algorithm was generated to predict the risk of complication based on histopathological parameters. A total of 28 paediatric patients were identified, among whom 10 developed post-operative complications (35%). The activity score at the recto-anal margin was higher among the patients with post-operative complications (mean 7.3±3.1 versus 4.8±3.1; p=0.04). The involvement of more than 5% colonic crypts with epithelial neutrophilic infiltration at the recto-anal margin was found to be an independent parameter that would stratify the patients into low-risk or high-risk group for developing complications (17% versus 64%; p=0.04). An association between UC disease activity at the recto-anal margin and post-operative J-pouch complications was determined. Potentially, this association suggests that a histopathological assessment of the recto-anal transitional zone may have value in guiding the surgeon on the risk of post-operative complications.

Histologic analysis of eosinophils and mast cells of the gastrointestinal tract in healthy Canadian children.

Many gastrointestinal (GI) disorders, including GI eosinophilia and inflammatory bowel disease, can be characterized by increased mucosal eosinophils (EOs) or mast cells (MCs). Normal mucosal cellular counts along the GI tract in healthy children have not been established for a Canadian pediatric population. To establish a benchmark reference, we quantified EO and MC from 356 mucosal biopsies of the GI tract obtained during upper and lower endoscopic biopsies of 38 pediatric patients in eastern Ontario. Mean total counts of EO varied for the 11 tissues we examined, from a low of 7.6±6.5/high-power field (HPF) (×40 [×400, 0.55mm(2)]) in the body of the stomach to a high of 50.3±17.4/HPF in the cecum. The lower GI tract (ileum, cecum, colon, sigmoid, and rectum) generally had higher total EO counts than the upper GI tract (antrum and body of stomach, duodenum, and duodenal cap) (combined average of 32.1±20.6 versus 19.3±15.8, respectively). Similarly, the number of mucosal MC was different in the various regions of the GI tract ranging from 0.04±0.2/HPF in the duodenal cap to 0.9±2.6/HPF in the ileum. Total counts for EO and MC in the lamina propria were not significantly different between sexes when adjusted for multiple testing. EO polarity was absent in many cases, irrespective of the GI region. These numeration and localization of EO and MC will provide normative data for upper and lower endoscopic GI biopsies in the pediatric population of Eastern Ontario.