Pancreatic Enzyme Use Reduces Pancreatitis Frequency in Children With Acute Recurrent or Chronic Pancreatitis: A Report From INSPPIRE.

INTRODUCTION: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP. METHODS: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors. RESULTS: Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation ( P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001). DISCUSSION: In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP.

Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2.

OBJECTIVE: To determine if mild-moderate hypertriglyceridemia is associated with increased development of chronic pancreatitis or pancreatitis-associated complications in children with acute recurrent or chronic pancreatitis. STUDY DESIGN: Longitudinal data from the INSPPIRE-2 (INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort of children with acute recurrent or chronic pancreatitis (n=559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.7 mmol/L), any hypertriglyceridemia (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate hypertriglyceridemia (150-499 mg/dL; 1.7-5.6 mmol/L), moderate hypertriglyceridemia (500-999 mg/dL; 5.6-11.3 mmol/L), and severe hypertriglyceridemia groups (≥1,000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed. RESULTS: In children with acute recurrent or chronic pancreatitis and hypertriglyceridemia, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in chronic pancreatitis prevalence. However, hypertriglyceridemia severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days. CONCLUSIONS: Mild-moderate hypertriglyceridemia in children with acute recurrent or chronic pancreatitis was not associated with increased pancreatitis frequency, nor increased development of chronic pancreatitis, but was associated with increased pancreatitis complications and disease burden. As a treatable condition, treatment of mild-moderate hypertriglyceridemia may be considered to reduce pancreatitis-associated complications and medical burden in children with acute recurrent or chronic pancreatitis.

Pediatric colonic adenocarcinoma: A deceptive case of gastroenteritis and constipation.

Adenocarcinoma of the colon is a rare diagnosis in pediatric patients. We present a previously healthy 15-year-old female who began experiencing escalating colicky abdominal pain and associated vomiting over 2 weeks in the setting of presumed acute gastroenteritis. A computed tomography scan revealed an obstruction in her descending colon. A multidisciplinary decision was made to perform a colonoscopy upon which a large, circumferential, friable lesion was discovered 40 cm from the anus. A colon decompression catheter was successfully inserted following controlled radial expansion (CRE) Balloon dilation to 13.5 mm beyond the mass, resulting in a significant discharge of fluid and gas. The patient underwent hemicolectomy with mass resection and colostomy. Biopsies confirmed poorly differentiated adenocarcinoma with "napkin-ring" morphology and positive lymph node metastasis with extranodal extension.

Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE), an inflammatory atopic disease of the esophagus, causes massive eosinophil infiltration, basal cell hyperplasia, and sub-epithelial fibrosis. To elucidate cellular and molecular factors involved in esophageal tissue damage and remodeling, we examined pinch biopsies from EoE and normal pediatric patients. An inflammation gene array confirmed that eotaxin-3, its receptor CCR3 and interleukins IL-13 and IL-5 were upregulated. An extracellular matrix (ECM) gene array revealed upregulation of CD44 & CD54, and of ECM proteases (ADAMTS1 & MMP14). A cytokine antibody array showed a marked decrease in IL-1α and IL-1 receptor antagonist and an increase in eotaxin-2 and epidermal growth factor. Western analysis indicated reduced expression of intercellular junction proteins, E-cadherin and claudin-1 and increased expression of occludin and vimentin. We have identified a number of novel genes and proteins whose expression is altered in EoE. These findings provide new insights into the molecular mechanisms of the disease.