A Rare Case of a Translocation-Associated Perivascular Epithelioid Cell Neoplasm (PEComa).

A perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm composed of perivascular epithelioid cells with distinctive histologic, immunohistochemical, and genetic features. PEComas arising from various anatomical sites have been reported, but gastrointestinal PEComas are extremely rare entities. Here, we discuss the clinical and pathological features of a gastrointestinal PEComa with a transcription factor E3 (TFE3) translocation in a 17-year old adolescent male with a clinical presentation of abdominal pain and gastrointestinal bleeding. Our case report provides insight into this rare entity as well as discusses the pathophysiological aspects of TFE3-SFPQ-associated GI PEComas and their management.

Implementing the Patient Health Questionnaire Modified for Adolescents to improve screening for depression among adolescents in a Federally Qualified Health Centre.

BACKGROUND: Depression, which is a serious medical illness, is prevalent worldwide and it negatively impacts the adolescent lifestyle. Adolescent depression is associated with adverse emotional and functional outcomes and suboptimal physical health. Over the last decade, it has been found that approximately 9% of teenagers meet the criteria for depression at any given time, and one in five teenagers have a history of depression during adolescence. Ninety per cent of paediatricians believe that recognition of child and adolescent depression is their responsibility; however, it has been reported that 46% lacked confidence that they could recognise depression. METHODS: In this study, adolescents between 12 and 17 years of age were screened during their well-child visits using the Patient Health Questionnaire Modified for Adolescents. A score of 10 or higher warrants a referral to a social worker and psychiatrist. The goals of this quality improvement project were to implement a standardised questionnaire and to improve the screening, diagnosis and treatment of depression in children from 12 to 17 years of age. RESULTS: It was found that the adolescent depression screening rate significantly improved within 6 months of implementing this quality improvement project. The screening rate improved to 50% by mid-cycle (Plan-Do-Study-Act (PDSA) cycle 3) and up to 70% at the end of the 6-month period (PDSA cycle 5). Improvement was noted among all providers, across all age groups, and in both male and female patients by the end of the study period. CONCLUSION: Standardised screening tests with a scoring system help providers to identify and monitor depression symptoms using a common language, especially in the outpatient clinical setting where the patient may be seen by different providers.

Paroxysmal Nocturnal Hemoglobinuria: Diagnostic Challenges in Pediatric Patient.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening hematologic stem cell disorder characterized by hemoglobinuria, thrombosis, and tendency for bone marrow failure. The rare incidence of PNH in children, its nonspecific clinical presentation, and occasional absence of hemoglobinuria make the diagnosis challenging. We present a case of a 17-year-old boy who was hospitalized with a history of recurrent abdominal pain, fever, and dark-colored urine. Laboratory tests revealed anemia, thrombocytopenia, and elevated inflammatory markers. Urinalysis was positive for protein and red blood cells, too many to be counted. Complement studies were within normal limits. Abdominal computed tomography showed a segment of the small bowel with wall thickening and signs of possible microperforation. Exploratory laparotomy revealed necrosis of the small bowel, and histological evaluation was suggestive of an autoimmune process with small vessel vasculitis. Bone marrow biopsy showed hypocellular marrow with a decreased number of myeloid cells, normal number of megakaryocytes, and signs of erythroid hyperplasia. Flow cytometry detected deficiency of CD59 leading to the diagnosis of PNH. The patient was treated with eculizumab infusions resulting in significant improvement. This case highlights the need for high clinical suspicion for rare entities such as PNH in patients presenting without hemoglobinuria.

Difficulty in the Clinical Diagnosis of Tularemia: Highlighting the Importance of a Physical Exam.

We report an 18-month-old male who presented with fever and nonspecific symptoms. He was evaluated for multiple differential diagnoses including Kawasaki disease and JIA and received treatment for them. After he was readmitted, tularemia was considered based on the physical exam finding of an ulcer on the scalp and enlarged lymph nodes. Tularemia titers were positive, and the patient was given the appropriate antibiotic and was discharged home. Follow-up of the patient showed complete resolution of symptoms. This is a case that demonstrates the importance of physical exam in identifying rare diseases presenting with common signs and symptoms.

Uneven Distribution of Microgranules in Divided Lansoprazole Tablets.

OBJECTIVES: Lansoprazole is a proton pump inhibitor commonly used in children <12 months of age despite a lack of efficacy and safety data in this age group. To achieve lower doses in this population, many divide standard oral disintegrating tablets. This study seeks to determine if the medication is equally distributed within the tablet to allow for accurate dosing. METHODS: Ten 15-mg Prevacid SoluTabs were divided. Each portion was dissolved separately (half A, B, and the residual "dust" C) and photographed. A magnified view of the image allowed for counting each microgranule. RESULTS: The mean number and standard deviation of microgranules in half A, B, and part C were 2514.7 ±â€Š130.5, 2342.9 ±â€Š130.1, and 49.4 ±â€Š38.8, respectively. The total number of microgranules per tablet was 4907 ±â€Š140.5. There was a statistically significant difference in the mean number of microgranules in half A versus B (P = 0.0086). CONCLUSIONS: There are statistically significant differences in the amount of lansoprazole-containing microgranules within each half of a divided tablet. Clinicians must determine whether this difference is clinically relevant when prescribing "divided" medication to children.

Eosinophilic esophagitis in children.

Eosinophilic esophagitis (EoE) is a relatively common chronic immune-mediated disease of the esophagus characterized clinically by symptoms of esophageal dysfunction that vary by age. Histologically, EoE results in marked esophageal eosinophilia despite treatment with high-dose proton pump inhibition. The cornerstone of treatment is dietary restriction and/or pharmacologic therapy, mainly with topical steroids. This review briefly describes dietary therapy, but focuses on the various medical options in the treatment of EoE, with an emphasis on steroid-based therapy. Numerous landmark studies are reviewed describing the symptomatic and histologic endpoints as well as safety data. The literature strongly supports the use of topical steroid therapy as a means of significantly decreasing eosinophilic mucosal disease. Specifically, high-dose fluticasone propionate appears to be very effective, and has been shown to result in the resolution of mucosal eosinophilia in a large percentage of treated patients. Long-term studies over many years will need to determine whether mucosal healing will change the natural history of this stricture-causing disease. In addition to topical therapy, various other drug-based therapies are reported, including newer immune-based monoclonal antibodies.

Correlation of health-related quality of life in children with inflammatory bowel disease, their parents, and physician as measured by a visual analog scale.

BACKGROUND AND AIMS: Inflammatory bowel disease has been shown to affect children's health-related quality of life (HRQOL) through the use of lengthy questionnaires. We examined whether a pediatric patient's HRQOL, measured by a rapid visual analog scale ("feeling thermometer"), correlates with the perceptions of the HRQOL as determined by the patient's pediatric gastroenterologist and parent(s). Additionally, we attempted to determine whether the HRQOL correlates with the patient's disease activity as determined by validated activity indices. METHODS: A cross-sectional study of pediatric patients (ages 7-21 years) who were diagnosed as having Crohn disease, ulcerative colitis, or indeterminate colitis was conducted from January 2011 to May 2011. Each participant (patient, parent(s), and treating pediatric gastroenterologist) completed feeling thermometers to determine the symptom burden as well as therapeutic burden of the patient. The parent(s) and doctor were blinded to the patient's results. Pediatric Ulcerative Colitis Activity Index or a Short Pediatric Crohn Disease Activity Index (S-PCDAI) was calculated. Correlations between the participant's perceived burdens as well as their calculated disease activity were determined. RESULTS: Sixty-seven children and their families participated, resulting in 101 visits. Patients had a mean age of 15.0 years, and there were 38 boys. There was a strong significant correlation between the patient's perceived symptom burden and that of the parent's (ρ 0.59, P < 0.001) and physician (ρ 0.48, P < 0.001). Similarly, there was a strong significant correlation between patient's perceived treatment burden and that of the parent treatment burden (ρ 0.49, P < 0.001) and, to a lesser degree, the physician (ρ 0.29, P < 0.003). The correlation coefficient was strongest between the physician's perception of the patient's symptom burden against the standard disease activity indices Pediatric Ulcerative Colitis Activity Index (ρ 0.69, P < 0.001) and Short Pediatric Crohn Disease Activity Index (ρ 0.65, P < 0.001). CONCLUSIONS: The patient's HRQOL was highly correlated to both the physician's and parent's perceptions as well as their disease activity. The feeling thermometer is a quick, easy-to-use, visual analog scale that can be implemented in everyday practice to measure a pediatric patient's HRQOL.

Role of thiopurine metabolite testing and thiopurine methyltransferase determination in pediatric IBD.

Thiopurines have been used in inflammatory bowel disease (IBD) for >30 years, and measurements of both thiopurine methyltransferase (TPMT) and thiopurine (TP) metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP), have been readily available. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Committee on Inflammatory Bowel Disease thought it appropriate to review the present indications for use of TPMT and TP metabolite testing. Substantial evidence demonstrates that TP therapy is useful for both Crohn disease and ulcerative colitis. Review of the existing data yielded the following recommendations. TPMT testing is recommended before initiation of TPs to identify individuals who are homozygote recessive or have extremely low TPMT activity, with the latter having more reliability than the former. Individuals who are homozygous recessive or have extremely low TPMT activity should avoid the use of TPs because of concerns for significant leukopenia. TMPT testing does not predict all cases of leukopenia and has no value to predict hypersensitivity adverse effects such as pancreatitis. Any potential value to reduce the risk of malignancy has not been studied. All individuals taking TPs should have routine monitoring with complete blood cell count and white blood cell count differential to evaluate for leukopenia regardless of TPMT testing results. Metabolite testing can be used to determine adherence with TP therapy. Metabolite testing can be used to guide dose increases or modifications in patients with active disease. Consideration would include either increasing the dose, changing therapy or for those with elevated transaminases or an elevated 6-MMP, using adjunctive allopurinol to help raise 6-thioguanine metabolites and suppress formation of 6-MMP. Routine and repetitive metabolite testing has little or no role in patients who are doing well and taking an acceptable dose of a TP.

Use of enteral nutrition for the control of intestinal inflammation in pediatric Crohn disease.

Exclusive enteral nutrition is an effective yet often underused therapy for the induction of remission in pediatric Crohn disease. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition formed the Enteral Nutrition Working Group to review the use of enteral nutrition therapy in pediatric Crohn disease. The group was composed of 5 pediatric gastroenterologists and 1 pediatric nutritionist, all with an interest and/or expertise in exclusive enteral nutrition. Specific attention was placed upon review of the evidence for efficacy of therapy, assessment of the variations in care, identification of barriers to its widespread use, and compilation of the necessary components for a successful program. The present guideline is intended to aid physicians in developing an enteral nutrition therapy program and potentially promote its use.

Benign transient hyperphosphatasemia in infants and children: a prospective cohort.

A total of 20 children with benign transient hyperphosphatasemia were prospectively evaluated with no additional investigations recommended except repeat serologic evaluation in 2-3 months. The average age of our patients was 2.5 years (range 1 year 2 months-5 years 10 months). The serum levels of alkaline phosphatase averaged 2383 IU/L (range 1013-5700 IU/L). Levels returned to normal within several months. This condition should be recognized by the clinician in order not to put patients through lengthy, expensive and unnecessary investigations.

Long-term efficacy of low-dose tricyclic antidepressants for children with functional gastrointestinal disorders.

OBJECTIVE: The aim of the study was to determine the long-term efficacy of the tricyclic antidepressant (TCA) drugs amitriptyline or imipramine in treating functional gastrointestinal disorders (FGIDs) in pediatric patients. MATERIALS AND METHODS: A retrospective chart review of children with a diagnosis of irritable bowel syndrome, functional dyspepsia, and functional abdominal pain diagnosed on the basis of the Rome III criteria was performed. Charts were analyzed for response to the medication and the duration of the response. RESULTS: A total of 98 patients took a TCA for an FGID. Of the 98 patients, 77 patients (78.6%) responded to the treatment for an average of 10.73 (range 1-45) months. CONCLUSIONS: TCAs are effective in treating FGIDs in pediatric patients for a long duration.

Benign transient hyperphosphatasemia in infants and children: a prospective cohort.

A total of 20 children with benign transient hyperphosphatasemia were prospectively evaluated with no additional investigations recommended except repeat serologic evaluation in 2-3 months. The average age of our patients was 2.5 years (range: 1 year 2 months-5 years 10 months). The serum levels of alkaline phosphatase averaged 2383 IU/L (range: 1013-5700 IU/L). Levels returned to normal within several months. This condition should be recognized by the clinician in order not to put patients through lengthy, expensive and unnecessary investigations.

Triple sugar screen breath hydrogen test for sugar intolerance in children with functional abdominal symptoms.

BACKGROUND: Sugar intolerance and functional gastrointestinal disorders are both common in school age children. Both may present with similar complaints such as abdominal pain, diarrhea and bloating. Lactose, fructose and sucrose hydrogen breath tests are widely used to detect sugar malabsorption. AIM: To determine the proportion of children with symptoms of functional gastrointestinal disorders (FGID) that have sugar intolerance as determined by using a breath hydrogen test. METHODS: We prospectively enrolled subjects with chronic abdominal pain, bloating and/or chronic diarrhea. All subjects underwent triple sugar screen hydrogen breath test (TSST) using the combined sugar solution. Breath hydrogen concentration ≥ 20 ppm above baseline was interpreted a positive test for sugar malabsorption. RESULTS: A positive hydrogen breath test consistent with sugar malabsorption was found in 5 out of 31 (16%) subjects. Three of these subjects were confirmed to have lactose malabsorption based on small bowel lactase enzyme analysis or subsequent lactose hydrogen breath test. One subject with positive TSST was diagnosed with fructose malabsorption based on dietary history; he improved on a limited fructose diet, and one was diagnosed to have gastric Crohn's disease. CONCLUSION: Approximately one in six children with symptoms of FGID had sugar intolerance as determined by the TSST.

Heat shock protein 27: induction by gastroduodenal reflux in vivo and augmentation of human esophageal mucosal cell growth in vitro.

OBJECTIVE: Acid exposure to esophageal epithelium leads to hyperplasia and mucosal thickening. This is associated with upregulation of antiapoptotic genes. Recently, heat shock proteins have been implicated in esophageal mucosal response to stress. We sought to determine the influence of gastroduodenal reflux on esophageal mucosal heat shock protein 27 gene (murine analog Hspb1, human HSPB1) expression in vivo and the effect of HSPB1 overexpression on proliferation of esophageal mucosal cells in vitro. METHODS: Balb/c mice underwent either anastomosis of gastroesophageal junction and first portion of duodenum to induce continuous gastroduodenal reflux (n = 14) or sham procedure (n = 12). Quantitative reverse transcriptase polymerase chain reaction was used to determine the influence of gastroduodenal reflux on Hspb1 expression. Immunofluorescent microscopy and immunoblotting were used to quantify changes in heat shock protein 27 protein expression. Lentiviral infection techniques were used to overexpress HSPB1 in human esophageal epithelial cells. Both 3-(4,5-dimethylthiazole-2-yl) 2,5,-diphenyl tetrazolium bromide and 5-bromo-2-deoxyuridine incorporation assays were used to assess cell proliferation. RESULTS: Expressions of Hspb1 and its protein product were increased in esophageal tissue after 12 weeks' reflux relative to sham control group. Expression was located mainly in hyperplastic epithelial cells. Overexpression of HSPB1 in human esophageal epithelial cells resulted in increased proliferation. CONCLUSIONS: Heat shock protein 27 is upregulated in response to gastroduodenal reflux and is a mediator of human esophageal epithelial cell proliferation and growth. This novel finding illustrates the importance of its expression in the development of inflammation and mucosal thickening associated with esophageal reflux.

Obesity is related to multiple functional abdominal diseases.

Analysis of the body mass index of pediatric patients with gastrointestinal complaints as a whole and by disease subgroup revealed a greater percentage of obese patients with constipation, gastroesophageal reflux, irritable bowel syndrome, encopresis, and functional abdominal pain compared with local and New Jersey control populations.

Clinical and endoscopic data in juvenile polyposis syndrome in preadolescent children: a multicenter experience from the United States.

OBJECTIVES: Juvenile polyposis syndrome (JPS) is a hereditary syndrome associated with several germline mutations, and carries a significant risk for future cancer development. Clinical data of JPS in children are sparse, and clinical guidelines are mainly derived from the adult population. In the present study, we describe the largest series of children diagnosed with JPS and present clinical, endoscopical, and histologic data. METHODS: A retrospective study of children with JPS was performed. Children were recruited from 3 academic pediatric gastroenterology centers. Clinical presentation, colonoscopic description, and histologic and demographic data were collected at initial presentation and at each future colonoscopy surveillance. RESULTS: Thirty-six children were included in the study with a mean age of 7.35 years and male to female ratio of 1.25:1. The most common clinical presentation was gastrointestinal bleeding (100%). Family history of colon cancer was noted in 28% of children. A total of 366 polyps were removed, of which 90.5% were pedunculated and 9.5% were sessile. Up to 4 colonoscopic, follow-up surveillances were documented: 21 children had 1 surveillance, 10 children had 2 surveillances, 3 children had 3 surveillances, and 1 child had 4 surveillances. Polyps were evenly distributed throughout the colon. Most of the polyps (99.2%) had benign histology (inflammatory changes) and 3 (0.8%) involved focal adenomatous changes. No adenocarcinoma was identified in any of the 366 polyps. CONCLUSIONS: Colonic polyps in JPS are rarely malignant during the pediatric age period. Our data suggest that the recommended colonic surveillance in children should be modified.

Familiarity of pediatricians with different commercially available neonatal and infant formulas.

To assess the familiarity of pediatricians with commercially available formulas and their use for cow's milk protein allergy and colic, a list of formulas was generated by visiting several grocery stores. Pediatricians were ask to indicate their familiarity with these and other "specialized" formulas with regard to protein and carbohydrate sources, energy content, hypoallergenicity, and indication for infant colic. The participants answered an average of 46% of the questions correctly. Respondents were very familiar with 27% of the formulas, and unfamiliar with 35%. The highest score was 70%, and 10% of the responders correctly answered 65% or more of the questions. Fifty-one percent correctly identified the protein source of the formulas; 32% correctly identified the carbohydrate source. The energy content of the formulas was correctly identified by 54%. These data suggest that pediatricians have a poor understanding of the content and appropriate use of neonatal and infant formulas.

Rotavirus causes hepatic transaminase elevation.

Rotavirus is one of the leading causes of acute gastroenteritis among children. While clinical complaints are generally intestinal including vomiting and diarrhea, there is evidence to suggest that disease outside the gastrointestinal tract occurs. This study examines the frequency of hepatic transaminase elevation in children with rotavirus gastroenteritis. Patients identified with rotavirus gastroenteritis by stool antigen testing between November 2005 and March 2006 had available serum analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, direct bilirubin, and creatinine phoshosphokinase (CPK). Chart review was conducted to identify patients with possible liver injury unrelated to rotavirus. Among the 92 patients identified with rotavirus during the study period, 75 had serum specimens available for testing. Fifteen patients (20%) had elevated ALT and AST, including one patient with an increase in AST, ALT, alkaline phosphatase, and total and direct bilirubin. The mean ALT elevation was 56 IU/L (range, 44 to 114 IU/L), and the mean AST elevation was 80 IU/L (range, 57 to 126 IU/L). Fifty-three patients (71%) had an increase in AST alone, and three patients (4%) had an increase in AST and alkaline phosphatase. The mean AST values in these groups were 61 IU/L (range, 42 to 110 IU/L) and 79 IU/L (range, 59 to 96 IU/L), respectively. In conclusion, rotavirus commonly causes elevation of liver transaminases.