Objectives-Acute pancreatitis is a necroinflammatory disease that leads to 210,000 hospitalizations in the United States annually. Recent reports suggest that there may be important differences in clinical features between infants/toddlers and older children. Thus, in this study we make a direct comparison between the pediatric age groups in presentation and management trends of acute pancreatitis. Patients and Methods-We examined all children (ages 0 to 20 years) admitted to Yale-New Haven Children's Hospital with pancreatitis between 1994 and 2007.Results-Two hundred seventy-one cases met inclusion criteria for acute pancreatitis. Infants and toddlers manifested fewer signs and symptoms of abdominal pain, epigastric tenderness, and nausea compared with older children (43% vs 93%; 57% vs 90%; and 29% vs 76%, respectively; P < 0.05 for all comparisons). They were more likely to be diagnosed by serum lipase than by amylase and to undergo radiographic evaluation (P < 0.05). They had a longer hospital stay (19.5 vs 4 days; P < 0.05) and were less likely to be directly transitioned to oral nutrition (14% vs 71%; P < 0.05).Conclusions-Infants and toddlers with acute pancreatitis present with fewer classical symptoms and are managed differently from older children. We believe these data will be helpful in evaluating and understanding treatment practices in this age group. Keywords acute pancreatitis; amylase; infants; lipase; toddlers Acute pancreatitis is a necroinflammatory disease of the pancreas that has many associated etiologies such as common bile duct stones, alcohol, trauma, medications, toxins, and ductal defects. Acute pancreatitis accounts for more than 210,000 annual hospital admissions (1) and, tallied with chronic pancreatitis, leads to 31,000 deaths per year (2). Although practice parameters for acute pancreatitis are currently evolving using primarily adult studies, information about children is lacking. Although in children there are several studies examining pancreatitis incidence and etiology (3-7), few have characterized their clinical presentation and management (8,9). We hypothesized that in our pediatric population of NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript acute pancreatitis in New Haven, Connecticut, there are also age-related differences in the management of acute pancreatitis. Indeed, we found that infants and toddlers differ from older children in clinical presentation, level of serum biomarker elevation, type of radiographic evaluation, length of hospitalization, and mode of nutrition. PATIENTS AND METHODS Study GroupA retrospective chart review was conducted at Yale-New Haven Children's Hospital, New Haven. Children (younger than 21 years) admitted between August 1994 and July 2007 were screened for International Classification of Diseases-9 codes pertaining to pancreatitis. The study was approved by the Yale University School of Medicine institutional review board. Details of the cohort, including referral trends for pancreatitis over time, eti...

The premature activation of digestive proenzymes, specifically proteases, within the pancreatic acinar cell is an early and critical event during acute pancreatitis. Our previous studies demonstrate that this activation requires a distinct pathological rise in cytosolic Ca(2+). Furthermore, we have shown that a target of aberrant Ca(2+) in acinar cells is the Ca(2+)/calmodulin-dependent phosphatase calcineurin (PP2B). In this study, we hypothesized that PP2B mediates in vivo protease activation and pancreatitis severity. To test this, pancreatitis was induced in mice over 8 h by administering hourly intraperitoneal injections of the cholecystokinin analog caerulein (50 microg/kg). Treatment with the PP2B inhibitor FK506 at 1 and 8 h after pancreatitis induction reduced trypsin activities by greater than 50% (P < 0.005). Serum amylase and IL-6 was reduced by 86 and 84% relative to baseline (P < 0.0005) at 8 h, respectively. Histological severity of pancreatitis, graded on the basis of pancreatic edema, acinar cell vacuolization, inflammation, and apoptosis, was reduced early in the course of pancreatitis. Myeloperoxidase activity from both pancreas and lung was reduced by 93 and 83% relative to baseline, respectively (P < 0.05). These data suggest that PP2B is an important target of the aberrant acinar cell Ca(2+) rise associated with pathological protease activation and pancreatitis.

Little is known about risk factors for biliary pancreatitis in children. Objectives We characterized cases of pediatric biliary pancreatitis, compared biliary with non-biliary cases, examined differences in presentation between younger and older children, and studied features distinguishing gallstone- from sludge-induced pancreatitis. Methods We evaluated 76 episodes of biliary pancreatitis from 271 cases of acute pancreatitis in children admitted to a tertiary care hospital from 1994 to 2007. Results Of the 76 cases, 55% had gallstones, 21% had sludge, and 24% had structural defects. Hispanic children had a 2.85 (p=0.01) and 5.59 (p=0.003) higher probability for biliary pancreatitis than white and black children, respectively. Median serum amylase and lipase in children with biliary pancreatitis were 64% and 49% higher, respectively, compared to other etiologies (p<0.05). In multiple logistic regression, aspartate aminotransferase (AST) was an independent predictor of biliary pancreatitis (OR=6.69, p=0.001). When comparing gallstone- with sludge-induced etiologies, obesity was an independent predictor (38% more prevalent, p<0.01) of gallstone cases. Conclusions Hispanic ethnicity is a risk factor and AST is a biomarker for biliary pancreatitis over other etiologies. Furthermore, obesity can distinguish gallstone- from sludge-induced pancreatitis. These findings may spur prospective studies to determine the optimal evaluation and management of children with biliary pancreatitis.

Cytosolic Ca(2+) (Ca(i)(2+)) flux within the pancreatic acinar cell is important both physiologically and pathologically. We examined the role of cAMP in shaping the apical-to-basal Ca(2+) wave generated by the Ca(2+)-activating agonist carbachol. We hypothesized that cAMP modulates intra-acinar Ca(2+) channel opening by affecting either cAMP-dependent protein kinase (PKA) or exchange protein directly activated by cAMP (Epac). Isolated pancreatic acinar cells from rats were stimulated with carbachol (1 muM) with or without vasoactive intestinal polypeptide (VIP) or 8-bromo-cAMP (8-Br-cAMP), and then Ca(i)(2+) was monitored by confocal laser-scanning microscopy. The apical-to-basal carbachol (1 muM)-stimulated Ca(2+) wave was 8.63 +/- 0.68 microm/s; it increased to 19.66 +/- 2.22 microm/s (*P < 0.0005) with VIP (100 nM), and similar increases were observed with 8-Br-cAMP (100 microM). The Ca(2+) rise time after carbachol stimulation was reduced in both regions but to a greater degree in the basal. Lag time and maximal Ca(2+) elevation were not significantly affected by cAMP. The effect of cAMP on Ca(2+) waves also did not appear to depend on extracellular Ca(2+). However, the ryanodine receptor (RyR) inhibitor dantrolene (100 microM) reduced the cAMP-enhancement of wave speed. It was also reduced by the PKA inhibitor PKI (1 microM). 8-(4-chloro-phenylthio)-2'-O-Me-cAMP, a specific agonist of Epac, caused a similar increase as 8-Br-cAMP or VIP. These data suggest that cAMP accelerates the speed of the Ca(2+) wave in pancreatic acinar cells. A likely target of this modulation is the RyR, and these effects are mediated independently by PKA and Epac pathways.

Hypercalcemia is an important etiology to consider in the evaluation of acute pancreatitis. Not only is it a treatable cause, but understanding the basis for this etiology may provide new insight into the common biochemical mechanisms involved in the pathogenesis of pancreatitis. We report a case of an 11 year-old girl with hypercalcemia due to primary hyperparathyroidism who developed recurrent pancreatitis. We review clinical and experimental data that implicate hypercalcemia as the cause and discuss mechanisms for the association. KEY WORDSacute pancreatitis, pancreatic acinar cell, calcium, hypercalcemia, hyperparathyroidism