1. Pediatric Pancreatitis

2. Educational Gaps
The incidence of acute pancreatitis has increased in pediatric patients over the past two decades, approaching the incidence in adults.
Clinicians should know : approaches to pancreatic rest and fluid management have changed, as have long-time teachings on the use of opiods and the institution of nutrition.

3. Objectives should be able to:
Differentiate between acute and chronic pancreatitis.
Know how to diagnose acute pancreatitis.
List common causes for acute, recurrent, and chronic pancreatitis
Explain the utility of clinical symptoms, biochemical testing, and radiographic imaging
Understand the management

4. Introduction An inflammatory condition of the pancreas
Acute pancreatitis is a reversible process, whereas chronic pancreatitis (CP) is irreversible
Differences between pancreatitis in children and adults, particularly in presentation, etiology, prognosis, and nature of acute recurrent pancreatitis (ARP). 

5. Acute Pancreatitis in Pediatrics

6. Epidemiology occurs in all age groups, even in infants.
3.6~13.2/10W, approaches to adults (greater awareness)

7. Pathophysiology Acinar cell injury
1. initiate the premature intracellular activation of trypsinogen to trypsin. Trypsin, in turn, activates other digestive proenzymes. The activated digestive enzymes then mediate acinar cell injury.
2. an aberrant unfolded protein response and the resultant endoplasmic reticulum stress may initiate apoptotic pathways and inflammatory signals.

9. Gallstone pancreatitis is a more common cause than previously believed.

10. >20% of reported cases
Multifactorial:
Sepsis
Shock
Hemolytic uremic syndrome(++)
Systemic lupus erythematosus
Virus like mumps virus

11. L-asparaginase
Valproic acid
Azathioprine
Mercaptopurine
Mesalamine
May disrupt acinar cell metabolism

12. not as high as previously thought
Unintentional blunt trauma
Child abuse

14. Metabolite: treatment can prevent recurrent episodes.
Disorders that cause hypercalcemia, hypertriglyceridemia, and inborn errors
Genetic: discuss later

15. Type 1: may elevated IgG4, diffuse or segmental enlargement of the pancreas, strictures of the pancreatic duct.
Type 2: more common in children
, association with inflammatory bowel disease and other autoimmune diseases
→respond to corticosteroid therapy.

16. Choledochal cysts
Pancreas divisum( 15%), related to SPINK-1 or CFTR gene
Annular pancreas

17. Pancreas divisum
胰腺分裂

18. Diagnosis
≥ two of three criteria: (1) Abdominal pain (2) Serum amylase or lipase > 3 times than the upper limit of normal (3) Imaging findings compatible with acute pancreatitis. Mild: >90%, limited to the pancreas and the peripancreatic fat Severe: pancreatic necrosis, involvement of other organs, cardiovascular collapse, infection, or fluid collections.
(1) abdominal pain suggestive of or compatible with acute pancreatitis (ie, abdominal pain of
acute onset, especially in the epigastric region)

19. ABDOMINAL PAIN
80% to 95% in pediatric patients who have acute pancreatitis.
Epigastric: 62% to 89%
Diffusely: 12% ~ 20%
Radiating to the back: 1.6%~5.6%
Nonverbal or encephalopathy-> irritability

20. Amylase and lipase Rise time- Amylase: 2~12 hours Lipase: 4 ~ 8 hours
May just one elevate
Other elevation cause

26. Management Pancreatic rest
Fluid support: 1.5 times maintenance IVF in first 24 hours
Nutrition: priming since 24~48hrs if mild( Regular meal. No low fat. 10% pain. Continue even elevated enzyme. TPN for prolonged ileus, pancreatic fistulae, or complicating abdominal compartment syndrome)

27. Management Antiemetics and analgesia: opioid( morphine)
Treat reversible cause( antibiotic is not routine)
Monitoring for complications.

28. Complications
Pancreatic fluid collections are the most common

29. Pseudocyst

30. Outcomes
better than in adults and are not correlated with initial amylase and lipase levels.
no existing scoring systems like APACHE (Acute Physiology and Chronic Health Evaluation) or the Ranson system used pediatrics.

31. Acute Recurrent Pancreatitis( ARP)

32. Definition
≥2 episodes of acute pancreatitis per year, or >3 episodes over a lifetime, in a patient without CP or a pancreatic pseudocyst
10% to 35% of patients will have recurrence

33. Etiology

34. Genetic mutation PRSS-1: cationic trypsinogen
Several mutations in the PRSS-1 gene that encodes cationic trypsinogen cause hereditary pancreatitis.
Autosomal dominant with an 80% penetrance.
The lifetime risk of pancreatic cancer is 40% or greater in these patients.

35. Genetic mutation SPINK-1: serine protease inhibitor Kazal type 1
Produced in acinar cells and acts as a defense for premature trypsinogen activation.
But most people who have these mutations, even when homozygous, do not develop pancreatitis.
Thought to be related to decreased ability to inactivate trypsin. But toxicity from misfolded protein, remain possible

36. Genetic mutation
CFTR: cystic fibrosis transmembrane conductance regulator
Disease modifiers
Lack other clinical features of cystic fibrosis or have mild disease in other organs and are pancreatic-sufficient at presentation, although some will develop pancreatic insufficiency over time.
the effect of many changes in the gene sequence on protein function is unknown.

37. Genetic mutation CTRC: chymotrypsin C gene
Encodes for the digestive enzyme chymotrypsin C
Disease modifiers.
Can inactivate trypsin in vitro

38. Duplication cysts- duodenum or stomach
Secondary to pancreaticobiliary obstruction
Difficult to detect

39. Management Genetic screening for PRSS-1 and SPINK-1 mutations
Sweat test-> indeterminate or low positive zone-> gene sequencing for CFTR
MRCP: anatomy
Pancreas divisum-> ERCP: sphincterotomy and stenting of the minor papilla
Endoscopy for mass lesion which obstruct the ampulla
Autoimmune pancreatitis: if MRCP suspect- IgG4
Systemic inflammatory disease, especially for Crohn disease
Ultrasonography or CT scan- to identify duplication cysts

40. Chronic Pancreatitis

41. Definition and epidemiology
A process leading to irreversible destruction of the pancreatic parenchyma and ducts and loss of exocrine function.
Classic cystic fibrosis is the most common cause in children
Incidence and prevalence in childhood are not known.

42. Etiology and pathophysiology
Causes of CP are the same as those of ARP
Results from the sequelae of long-standing destructive inflammation
Fibrosis

43. Diagnosis
Clinical and based on a combination of symptoms, imaging studies, and functional insufficiency
Diagnosis often is delayed
With advanced disease, amylase and lipase levels will not be elevated, even in the presence of disabling pain.

44. Clinical features
Pain: mild to intense, usually epigastric, constant or intermittent, deep and penetrating, radiation to the back, episodic.
- obstruction of pancreatic ducts by fibrosis or stone
- inflammation of the parenchyma
- perineural inflammation
- pain imprinting in the peripheral or central nervous system

45. Clinical features
Malabsorption: weight loss, fatty stools, or diarrhea
Jaundice from extrahepatic biliary obstruction caused by pancreatic fibrosis or a pseudocyst
Upper gastrointestinal hemorrhage from venous thrombosis
Diabetes

46. Pancreatic function testing
Identify pancreatic insufficiency:
- Duodenal intubation with secretin-cholecystokinin stimulation: standard for diagnostic testing
- Pancreatic secretions collected at upper endoscopy: underestimates
- Fecal elastase: poor sensitivity
trypsin output <50 U/kg/h as the reference standard
Elastase, a kind of proteinase, Elastase breaks down elastin, an elastic fibre that, together with collagen, determines the mechanical properties of connective tissue.

47. Management Pain : acetaminophen; narcotics/ nerve ablation/ surgery
Pancreatic enzyme supplement
Endoscopic treatment for ductal strictures or pancreatic duct stones
Surgical intervention: partial resection; Total pancreatectomy with islet cell auto-transplant
Diabetes: insulin
only medical center west of the Mississippi UCSF
harvesting functioning islets from the patient's own diseased pancreas and then infusing them into the portal vein, where they migrate to the liver.

48. Complications
The pain may vacillate in intensity and frequency, but it will not resolve with time
Diabetes may take 2 or 3 decades to become clinically significant
In hereditary pancreatitis, pancreatic cancer appears first in the fourth decade (incidence of 0.5%)

49. Summary Increasing prevalence in pediatrics
Different etiologic: gallstone; trauma; genetic; idiopathic
Diagnosis: symptom, lab, image
Feeding: early, non-low fat
Chronic-> irreversible