Pediatric Gastrointestinal Histopathology in Patients With Tetratricopeptide Repeat Domain 7A (TTC7A) Germline Mutations: A Rare Condition Leading to Multiple Intestinal Atresias, Severe Combined Immunodeficiency, and Congenital Enteropathy.

Mutations in the tetratricopeptide repeat domain 7A (TTC7A) gene are a rare cause of congenital enteropathy that can result in significant morbidity. TTC7A deficiency leads to disruption of the intestinal epithelium. The histopathology of this condition has been partly described in case reports and clinical studies. This manuscript describes an in-depth investigation of the pediatric gastrointestinal pathology of the largest histologically examined cohort with confirmed TTC7A mutations reported to date and, for the first time, compared the findings to age-matched and sex-matched control patients with intestinal atresia not thought to be associated with TTC7A mutations. Hematoxylin and eosin-stained slides of endoscopically obtained mucosal biopsies and surgical resection specimens from 7 patients with known TTC7A mutations were examined retrospectively. The microscopic findings were found to be on a spectrum from atresia-predominant to those with predominantly epithelial abnormalities. Several unique histopathologic characteristics were observed when compared with controls. These included neutrophilic colitis and prominent lamina propria eosinophilia throughout the gastrointestinal tract. Striking architectural abnormalities of the epithelium were observed in 4 of the 7 patients. The 5 patients with intestinal atresia demonstrated hypertrophy and disorganization of the colonic muscularis mucosae accompanied by bland spindle cell nodules within the intestinal wall. The components of the latter were further elucidated using immunohistochemistry, and we subsequently hypothesize that they represent obliterated mucosa with remnants of the muscularis mucosae. Finally, atrophic gastritis was noted in 4 patients. In conclusion, the unique histopathologic characteristics of TTC7A mutation-associated enteropathy described herein more fully describe this novel disease entity in infants who present with congenital enteropathy or enterocolitis.

Leukocytoclastic vasculitis in an adolescent with ulcerative colitis: Report of a case and review of the literature.

An adolescent female with long-standing, difficult-to-control ulcerative colitis developed leukocytoclastic vasculitis, a rare cutaneous extra-intestinal manifestation of the inflammatory bowel disease. The authors provide a literature review on leukocytoclastic vasculitis complicating ulcerative colitis. Furthermore, the clinical features of leukocytoclastic vasculitis are compared and contrasted with the more common cutaneous extra-intestinal manifestations of inflammatory bowel disease, erythema nodosum, and pyoderma gangrenosum.

Esophageal foreign bodies and eosinophilic esophagitis--the need for esophageal mucosal biopsy: a 12-year survey across pediatric subspecialties.

BACKGROUND: Esophageal foreign body impaction (EFBI) is a common problem requiring urgent endoscopy. EFBI may be the first sign of underlying esophageal pathology, yet mucosal biopsies are rarely performed. METHODS: We report a retrospective analysis of 572 children requiring removal of an EFBI over a 12-year period by pediatric otolaryngologists (ENT), surgeons (PS), and gastroenterologists (PGI). The method of removal [direct laryngoscopy (DL), rigid endoscopy (RE), flexible endoscopy (FE)], type of foreign body (inanimate or food), whether mucosal biopsies were performed, and histologic findings of biopsy samples were recorded for each patient. RESULTS: Foreign body removal was most commonly performed by PGI (298 [52 %]); the remaining were equally distributed between ENT (136 [24 %]) and PS (138 [24 %]). The method of foreign body removal used by ENT was RE (89 %), DL (8 %), and FE (3 %). Pediatric surgery preferred FE (62 %), followed by RE (27 %) and DL (11 %). Pediatric gastroenterology used FE exclusively. Esophageal biopsies were never performed by ENT or PS; PGI performed esophageal biopsies more commonly in children with meat bolus impactions (50 %) than in children with inanimate foreign bodies (12 %). Mucosal pathology was more common in children with meat bolus impaction (100 %) than in children with inanimate foreign bodies (45 %). CONCLUSIONS: Esophageal mucosal biopsy should be considered for all children with EFBI not attributed to stricture, particularly those with meat bolus impaction.

Upper gastrointestinal bleeding in children: an 11-year retrospective endoscopic investigation.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) may present as hematemesis, coffee-ground emesis, or melena requiring esophagogastroduodenoscopy (EGD) for diagnosis and/or therapy. Worldwide, differences exist for the etiology of UGIB reflecting geographical differences in common disease states. In the past 25 years, there have been improvements in endoscopic optics. This study was undertaken to determine: 1) if identifying a bleeding source in UGIB have improved with better endoscopic optics, 2) geographic differences in causes of UGIB, 3) differences in severity of UGIB based on clinical factors, and 4) the likelihood of finding a bleeding source based on symptom duration and time to endoscopy. METHODS: A retrospective chart review was made on children having EGD for evaluation of UGIB. Data collected included type, etiology, and degree of bleeding. RESULTS: Of 2569 diagnostic procedures, 167 (6.5%) were performed for UGIB. The most common presentation was hematemesis (73.4%). Melena was associated with lower hemoglobin levels and higher transfusion rates. A source of UGIB was found in 57.0%, no cause in 11.4% and a questionable cause in 29.7%. A source was found less commonly in children with a history of UGIB less than one month and in those undergoing endoscopy over 48 hours after a bleeding episode. CONCLUSIONS: Improved endoscopic optics has not changed diagnostic ability for UGIB. Etiologic differences for UGIB in children from varying geographic areas are related to indication for endoscopy, patient selection, and co-morbid conditions. Duration of bleeding and time to endoscopy after a bleeding episode may help predict when endoscopy should be performed to determine a bleeding source.

Juvenile polyps and juvenile polyp syndromes in children: a clinical and endoscopic survey.

UNLABELLED: In children, most colonic polyps are juvenile polyps with negligible risk for malignant transformation. The exception is juvenile polyposis syndrome (JPS) where there is a risk for developing colon cancer. The authors studied differences in clinical features and colonoscopic findings in children with solitary juvenile polyps (SJP), multiple juvenile polyps (MJP), and JPS. METHODS: Children were identified as SJP (1 polyp), MJP (2-4 polyps), or JPS (>5 polyps). Demographic data, laboratory values, family history, and colonoscopic findings were recorded. RESULTS: Children having polypectomy had juvenile polyps (93%), adenomatous polyps (5%), and Peutz-Jegher syndrome (3%). Juvenile polyps were classified as SJP (67%), MJP (16%), and JPS (17%). Children with SJP were younger, were more likely to have polyps limited to the rectosigmoid colon, and had larger polyps than children with MJP and JPS. Anemia was more common in JPS than MJP and SJP. CONCLUSION: Clinical and endoscopic findings differ between SJP, MJP, and JPS.

A multicenter, randomized, open-label, pharmacokinetics and safety study of pantoprazole tablets in children and adolescents aged 6 through 16 years with gastroesophageal reflux disease.

Children with gastroesophageal reflux disease (GERD) may benefit from gastric acid suppression with proton pump inhibitors such as pantoprazole. Effective treatment with pantoprazole requires correct dosing and understanding of the drug's kinetic profile in children. The aim of these studies was to characterize the pharmacokinetic (PK) profile of single and multiple doses of pantoprazole delayed-release tablets in pediatric patients with GERD aged 6 to 11 years (study 1) and 12 to 16 years (study 2). Patients were randomly assigned to receive pantoprazole 20 or 40 mg once daily. Plasma pantoprazole concentrations were obtained at intervals through 12 hours after the single dose and at 2 and 4 hours after multiple doses for PK evaluation. PK parameters were derived by standard noncompartmental methods and examined as a function of both drug dose and patient age. Safety was also monitored. Pantoprazole PK was dose independent (when dose normalized) and similar to PK reported from adult studies. There was no evidence of accumulation with multiple dosing or reports of serious drug-associated adverse events. In children aged 6 to 16 years with GERD, currently available pantoprazole delayed-release tablets can be used to provide systemic exposure similar to that in adults.

Safety of blind percutaneous liver biopsy in obese children: a retrospective analysis.

GOAL: To determine the safety and adequacy of blind percutaneous liver biopsy (PLB) in obese children. BACKGROUND: PLB is an important diagnostic tool that, while invasive, enjoys a relatively low major complication rate. An ever increasing reason for pediatric liver biopsy is nonalcoholic fatty liver disease associated with obesity. There is a lack of data assessing the safety of liver biopsy in obese compared to nonobese children. STUDY: A retrospective study of all children over 5 years of age having PLB was conducted. Data collected included age, gender, weight, height, BMI, reason for biopsy, number of passes, biopsy length, number of portal triads per biopsy, and complication rates. RESULTS: A total of 107 biopsies were reviewed. All biopsies were successful. Overall, major complications occurred in 1.3% and minor complications in 8.4%; there were no deaths. Comparison revealed no difference for number of passes (1.5±0.7 vs. 1.7±0.7), biopsy length (2.0±1.3 cm vs. 1.5±1.1 cm), number of portal tracts per biopsy (9.8±5.8 vs. 9.9±3.4), or complication rates (major: 0% vs. 1.3%; minor: 10.0% vs. 7.8%) between obese and nonobese children. CONCLUSION: Blind PLB can be safely carried out in obese children with no increase in complication rate compared with nonobese children. Similarly, there is no difference in number of passes, biopsy size, portal triads per biopsy, or biopsy success for obese children.

Age-related differences in granulomatous gastritis: a retrospective, clinicopathological analysis.

BACKGROUND: Granulomatous gastritis (GG) is an uncommon pathological finding that may accompany systemic disease, infections, foreign body reaction, malignancy or vasculitis, but may also be an isolated finding. Clinical and pathological features of GG have been systematically evaluated in adults but not children. OBJECTIVES: To compare clinical and pathological features of GG in adults and children, and also determine the prevalence of GG in children from a single centre. METHODS: A retrospective analysis of 23 children and 23 adults with GG was conducted. Demographic and clinical information was recorded for each patient. Gastric biopsy specimens were evaluated for the presence of gastritis, infectious organisms, and number and location of the granulomas. RESULTS: Children were a mean+/-SD age of 12.5+/-3.0 years, had a male predominance, and were most often Caucasian. Adults were a mean+/-SD age of 49.2+/-13.2 years, had a female predominance, and were most often African-American. Primary diagnoses were Crohn's disease in children, and sarcoidosis and isolated GG in adults. In both groups, granulomas were most often located in the antrum, with no difference in the number of granulomas per biopsy between children and adults. All biopsy specimens were negative for acid-fast bacilli and fungal organisms; Helicobacter pylori infection was uncommon. Overall prevalence of GG in children in this study was 1.7% for all diagnostic upper endoscopies. CONCLUSION: Differences in aetiology of GG between children and adults reflect age-specific disease states. Gender differences can be partially explained by gender differences intrinsic to the underlying aetiology. Irrespective of the underlying aetiology, the number and location of granulomas are similar in children and adults.

Critical analysis of caregiver perceptions regarding gastrostomy tube placement.

BACKGROUND: Gastrostomy tubes (GT) are often required to safely provide nutrition in children with feeding disorders and aspiration risk. The need for a GT brings with it known risks, complications, and benefits, but caregivers may have unspoken concerns and expectations. The present study was done to assess caregiver concerns, expectations, and satisfaction with GT placement in children. METHODS: A two-part retrospective and prospective study was conducted to assess caregiver concerns and expectations related to GT placement, to determine which concerns and expectations came to fruition, and to rate overall satisfaction with the GT. Questionnaires were used to collect data before and after GT placement. A visual analog scale (VAS) score was used to determine degree of concern and satisfaction. RESULTS: Sixty-four children (19 retrospective, 45 prospective) completed the study. Concern score by VAS was evenly distributed with a mean value of 47.4 +/- 31.8. Concerns were realized in 25%; expectations were met in 93%. Feeding time decreased following GT placement. Satisfaction was reported as satisfied (23.6%), pleased (16.4%), or very pleased (60.0%). CONCLUSIONS: Despite pre-placement concerns, most caregivers reported being pleased with the GT following placement. Concerns that occurred were of minor medical significance. Most expectations were met, in particular improved nutrition. The present study provides insight into caregiver concerns and expectations, and which are likely to occur. This information can be useful when counseling caregivers of children requiring GT.

Hepatic iron overload in children with sickle cell anemia on chronic transfusion therapy.

Hepatic iron overload is a serious complication of chronic transfusion therapy in patients with sickle cell disease (SCD). No firm consensus has been reached with regard to correlation between hepatic iron content (HIC) and variables including age, number of transfusions, and serum iron makers. Also, the role of HIC in determining hepatic injury is not well established. There is scarcity of data on chronically transfused children with SCD and no other confounding liver pathology. We aimed to further explore relationships between these variables in a cohort of children with SCD on chronic transfusion therapy naive to chelation. Liver biopsies obtained before starting chelation therapy from 27 children with sickle cell anemia receiving chronic transfusion therapy were evaluated for histologic scoring and determination of HIC. Average serum ferritin and iron saturation values were determined for 6 months before biopsy. Duration and total volume of transfusion were obtained from the medical records. All children were negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections. Mean age at biopsy was 10.95+/-3.34 years. Mean duration and total volume of transfusions were 50.0+/-26.6 months and 17.4+/-9.6 L, respectively. Pearson product-moment bivariate correlation coefficients indicated significant correlations between HIC and histologic iron score, serum ferritin, iron saturation, age, and transfusion volume. After adjusting for transfusion volume, a significant correlation was only seen between HIC and transfusion volume. Mean HIC was 21.8+/-10.4 mg/g dry weight, with fibrosis observed in 10 patients and lobular inflammation in 9. HIC was higher in biopsies with fibrosis (28.2+/-3.8 mg/g) than biopsies without fibrosis (17.6+/-18.3 mg/g; P=0.012). HIC did not differ between biopsies with lobular inflammation (25.5+/-4.0 mg/g) and biopsies without inflammation (19.9+/-2.5 mg/g; P=0.22). These findings show that transfusion volume provides more insight on hepatic iron overload than serum iron markers.