The present study provides preliminary evidence for a relation between clinical presentation, specific types of inflammatory cell infiltrates, and aspects of psychological functioning in children with FD. Rome III subtyping, adopted for adult dyspepsia, may be relevant to the pediatric population.

The aims of the current study were to determine the activation states of antral eosinophils and mast cells and to evaluate the interactions of antral inflammatory cells with gastric emptying and electrogastrography (EGG) in 30 pediatric patients with functional dyspepsia. Eosinophil degranulation was moderate in 42% and extensive in 54% of patients. Mast cell degranulation was > 50% in 81% of patients. Elevated mast cell density was associated with slower one hour gastric emptying and increased preprandial dysrhythmia. Mast cell density correlated with the preprandial percentage tachygastria. CD3+ cell density correlated with the preprandial percentage tachygastria also, but only in patients with increased eosinophil density. In conclusion, antral eosinophils and mast cells are significantly activated in pediatric functional dyspepsia. Mast cell density is associated with delayed gastric emptying and preprandial dysrhythmia, suggesting that there may be an interaction between antral inflammation and gastric electromechanical dysfunction in the pathophysiology of pediatric functional dyspepsia.

Both mucosal inflammation and psychologic dysfunction have been implicated in irritable bowel syndrome (IBS). While some relationships between inflammation (mast cells and eosinophils) and depression have been reported in adults with IBS, relationships between inflammation and psychologic function have not been studied in children and adolescents. The aims of the current study were to: (1) assess densities of colonic mast cells, eosinophils, and TH17 cells in youth with IBS; and, (2) explore relationships between these cells and specific IBS symptoms and psychologic functioning. Utilizing previously obtained biopsies from the descending and rectosigmoid colons, densities were determined for mast cells, eosinophils, and TH17 cells, respectively, in 37 youth with IBS and 10 controls. In IBS patients, densities were assessed in relation to specific IBS symptoms and in relation to self-report anxiety and depression scores. In both the descending and rectosigmoid colons, densities of mast cells, eosinophils, and TH17 cells were higher in IBS patients as compared to controls. In IBS patients, rectosigmoid mast cell density was higher in those reporting pain relief with defecation. Also, in IBS patients, rectosigmoid eosinophilia was associated with higher anxiety scores and eosinophil density correlated with depression scores. In the descending colon, eosinophil and mast cell densities both correlated with depression scores. In conclusion, mucosal inflammation (mast cells and eosinophils) is associated with pain relief with defecation and with anxiety and depression in youth with IBS. Chronic or recurrent abdominal pain affects a substantial proportion of children and adolescents 1,2. The majority of youth with chronic abdominal pain will not have an identified organic disease but will report symptoms consistent with one of the functional gastrointestinal disorders (FGIDs) as defined by Rome criteria 3,4. There are four pain related FGIDs with irritable bowel syndrome (IBS) being one of the two most common 5. Rome IV, the most current version of Rome criteria, defines IBS by the presence of one of the following symptoms: pain related to defecation, pain associated with a change in stool frequency, or pain associated with a change in stool form 4. IBS is further subcategorized as IBS with predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), mixed IBS with alternating constipation and diarrhea (IBS-M), and as unsubtyped 4,6. Among a variety of other factors, visceral hyperalgesia, inflammation and psychosocial factors have been highly implicated in the pathogenesis of IBS 7,8. Inflammatory cells which have been evaluated in IBS include mast cells, eosinophils, and lymphocytes, particularly T cells. Mast cells have been highly implicated in IBS pathogenesis in both IBS-C and IBS-D 9,10. IBS has been associated with an increase in the density of degranulating mast cells, while the density of mast cells in close proximity to enteric nerves correlates with abdominal pain severity 11 .

Headaches and abdominal pain are among the most common pediatric pain conditions. Mast cells have been implicated in the pathophysiology of migraines, as well as functional dyspepsia (FD) and irritable bowel syndrome (IBS). The primary aims of the current study were to assess headache prevalence in patients with FD and to assess the association between headaches and mucosal mast cells and eosinophils. An additional aim was to explore associations of headache with other symptoms.We conducted a cross-sectional retrospective chart review of 235 consecutive patients with chronic abdominal pain. All patients had completed a standardized questionnaire as part of their routine clinical evaluation. Both gastrointestinal and non-gastrointestinal somatic symptoms were included in the analysis. All patients diagnosed with FD had undergone upper endoscopy with biopsies obtained from the gastric antrum and duodenum and these specimens were utilized to assess eosinophil and mast cell densities, respectively.Overall, 86% of patients fulfilled Rome IV criteria for FD. Headache was reported by 73.8% of FD patients versus 45.2% of non-FD patients (P = .001). Duodenal mast cell densities were significantly increased in those reporting headaches. Headache was not associated with any specific gastrointestinal symptoms but was associated with a wide array of non-gastrointestinal symptoms including fatigue, dizziness, muscle pain, joint pain, and chest pain.Headaches are common in children and adolescents with abdominal pain and, utilizing Rome IV criteria, are specifically associated with FD. In patients with FD, headaches are associated with increased duodenal mast cell density and a variety of somatic symptoms, all of which are possibly the result of mast cell activation.

Background Nausea is a common symptom in youth with chronic abdominal pain. The aims of the current study were to assess: 1) the frequency of nausea in patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS), respectively, as defined by Rome IV criteria; and, 2) relationships between nausea and mucosal inflammation as defined by antral and duodenal eosinophil and mast cell densities. A secondary aim was to assess relationships between nausea and other gastrointestinal symptoms, non-gastrointestinal somatic symptoms, and psychological dysfunction. Methods Records from patients with pain associated functional gastrointestinal disorders were retrospectively reviewed for gastrointestinal and somatic symptoms and anxiety, depression, and somatizations scores as assessed by the Behavior Assessment System for Children (BASC-2). In addition, previous gastric and mucosal biopsies were assessed for mast cell and eosinophil densities, respectively. Results 250 patients, ages 8 to 17 years, were assessed. Nausea was reported by 78% and was equally prevalent in those with FD alone, those with IBS alone, and those with both FD and IBS. Nausea was associated with increased mean (21.4 vs. 17.5) and peak (26.2 vs. 22.9) duodenal mast cell densities as compared those without nausea. Nausea was also associated with a wide variety of individual gastrointestinal symptoms, as well as headaches, fatigue, and dizziness. Lastly, nausea was associated with elevated self-report scores for anxiety (55.2 vs. 50.0), depression (50.2 vs. 46.1), and somatization (70.3 vs. 61.8). Conclusions Nausea is common in children and adolescents with pain-associated FGIDs as defined by Rome IV and is not unique to either FD or IBS. Nausea is associated with increased mucosal mast cell density, non-gastrointestinal somatic symptoms, and psychologic dysfunction.

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Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response to chemotherapy); and a good clinical outcome group with 5 cases (all of which responded well to chemotherapy). We excluded the small cell variant of HB from the study because its poor clinical outcome is well known. To be placed in the aggressive group we used the following criteria: < 70% necrosis following chemotherapy or recurrence/distant metastasis following chemotherapy. From tissue obtained before chemotherapy, 1 representative block of formalin-fixed, paraffin-embedded tissue was selected for immunohistochemistry. Following review of published literature, antibodies were selected to detect Survivin, PLK-1, Cytokeratin19 (CK19), N-Myc, Yap, Notch2, Hes1, Hes5, and C-Myc. Our results show that Survivin, CK19, and Yap have a diffuse (> 75%) positive staining of tumor cells in the aggressive tumors compared with good outcome tumors. However, staining for Yap was weak. Interestingly, there was loss of nuclear expression of C-Myc in majority of tumor cells in aggressive tumors, whereas nuclear staining was retained in most tumor cells of good responders. The N-Myc and PLK-1 immunostains did not reveal any significant differences in the 2 groups of HB. The immunostains for Notch2, Hes1, and Hes5 showed weak to moderately strong staining in tumor cells, but there was no obvious difference in the 2 groups. Our pilot study suggests that in nonsmall cell HB, diffusely increased expression of Survivin and CK19, and loss of nuclear expression of C-Myc marks the tumors as having an aggressive course.