Pediatric Pancreatitis - Rivin

An inflammatory condition of the pancreas
Acute pancreatitis is a reversible process,
whereas Chronic pancreatitis (CP) is irreversible

Acinar Cell Injury

1. Pediatric Pancreatitis W. P. Rivindu H. Wickramanayake Group no. 04a 6 th Year 1 st Semester – 2020 April Tbilisi State Medical University, Georgia

2. Introduction An inflammatory condition of the pancreas Acute pancreatitis is a reversible process, whereas C hronic pancreatitis (CP) is irreversible Differences between pancreatitis in children and adults, - particularly in - Presentation , - Etiology , - Prognosis , and - Nature of acute recurrent pancreatitis (ARP). 

3. Epidemiology Occurs in all age groups, even in infants. approaches to adults   (greater awareness) Worldwide , the  incidence of acute pancreatitis  ranges between 5 and 80 per 100,000 population, with the highest   incidence  recorded in the United States and Finland. Acute Pancreatitis in Pediatrics

4. Pathophysiology Acinar C ell I njury 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.

5. Biliary disorders - Gallstone pancreatitis is a more common cause than previously believed Systemic conditions - >20% of reported cases - Multifactorial - Sepsis - Shock - Hemolytic Uremic Syndrome(++) - Systemic Lupus Erythematosus - Viruses such as Mumps virus and so on Causes of Acute Pancreatitis in Children

6. 3. Medications - L- asparaginase - Valproic acid - Azathioprine - Mercaptopurine - Mesalamine 4. Trauma - N ot as high as previously thought - Unintentional blunt trauma - Child abuse 5. Idiopathic 6. Infections - Treatment can prevent recurrent episodes.

7. 7. Metabolic disorders - Disorders that cause hypercalcemia , hypertriglyceridemia, and inborn errors 8 . Genetic / Hereditary diseases 9 . Autoimmune Pancreatitis - 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.

8. 12. Anatomic Pancreaticobiliary Abnormalities - Pancreas divisum ( 15%), related to SPINK-1 or CFTR gene Choledochal cysts Annular pancreas

9. Pancreas divisum

10. Diagnosis ≥ two of three criteria: ( 1) Abdominal pain - suggestive of or compatible with acute pancreatitis ( ie , abdominal pain of acute onset, especially in the epigastric region ) ( 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 .

11. 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 Amylase & Lipase Rise time - Amylase : 2~12 hours - Lipase : 4 ~ 8 hours

12. Pediatric Conditions with Elevation of Amylase or Lipase

13. Utility of Radiographic Imaging for Diagnosis of Pancreatitis

14. Management Pancreatic R est 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. Total Parenteral Nutrition for prolonged ileus, pancreatic fistulae, or complicating abdominal compartment syndrome) Antiemetics and analgesia: opioid( morphine ) Treat reversible cause( antibiotic is not routine ) Monitoring for complications.

15. Complications Pancreatic fluid collections are the most common

16. Pseudocyst

17. 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 .

18. Acute Recurrent Pancreatitis (ARP) ≥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

19. Etiology

20. 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. 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

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

22. Duplication C ysts - D uodenum or S tomach - Secondary to pancreaticobiliary obstruction - Difficult to detect

23. 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

24. Chronic Pancreatitis 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. Causes are the same as those of ARP Results from the sequelae of long-standing destructive inflammation Fibrosis

25. 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 .

26. 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

27. 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

28. Pancreatic Function T esting 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 - Breaks down  elastin, an  elastic fibre that , together with  collagen, determines the mechanical properties of  connective tissues.

29. 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 %) Depression

30. 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 (Harvesting functioning islets from the patient's own diseased pancreas and then infusing them into the portal vein, where they migrate to the liver .) Diabetes: insulin

31. Summary Increasing prevalence in pediatrics Different etiologic: - Gallstone; Trauma; Genetic; I diopathic Diagnosis: - Symptoms, L ab, I mage Feeding: - Early, Non-low fat Chronic  irreversible

32. Questions All of the following may be used as part of criteria to make a diagnosis of Acute Pancreatitis in a child EXCEPT: a . Epigastric pain x 2 days b . Amylase level 3 times upper limits of normal c . Lipase level 2 times upper limits of normal d . Ultrasound demonstrating pancreatic and peri ‐pancreatic edema e . Computer tomography scan demonstrating diffuse pancreatic swelling All of the following genes have been implicated in ARP and/ or CP EXCEPT: a . CFTR b . SPINK1 c . PRSS1 d . SBDS e . CTRC

33. 3. Your patient follows‐up in the clinic after her discharge and wants to discuss how to prevent further episodes of pancreatitis.  You recommend all the following as options EXCEPT: a . Antioxidants/micronutrients b . Low‐fat diet c . Pancreatic enzymes d . Antibiotics 4. Potential complications of chronic, recurrent pancreatitis includes chronic pain syndrome.   Patients presenting with chronic, recurrent pancreatitis and chronic pain need to be particularly screened for: a . Eating disorders b . Depression c . Obesity d . Learning disability

34. 5. A 14 year old female has had her second episode of acute pancreatitis. Her evaluation to date has shown a normal abdominal ultrasound, normal triglyceride and calcium, a negative sweat chloride test and no evidence for infectious, metabolic or drug induced pancreatitis. You have decided to perform further imaging as part of the evaluation. The best option in this setting would be: a . Repeat abdominal Ultrasound b . MRCP c . ERCP d . Endoscopic Ultrasound

35. Thank You! Rivin ..®