Acute & Chronic Pancreatitis

1. Acute & Chronic Pancreatitis Armed Forces Academy of Medical Sciences

2. Alexander the Great in 3rd century B.C. • Age 33 returned to Babylon from Persian victories • Celebrated with his generals and “ETOH flowed freely” • Next day he was seized with abdominal pain • Tx: immersion in waters of Euphrates • 1st record of chronic pancreatitis in 1787 • affluent, social man seized with diabetes • autopsy showed pancreas filled with stones

3. Pancreatic Anatomy

4. AP - Introduction • Incidence 1-5/10,000/yr • Overall Mortality 2-5% • 180,000 Hospitalizations/year US • 2300 Deaths/year US

5. AP • 80% mild(interstitial or edematous) • 20% severe (necrotizing) • 40-70% severe cases infected • Mortality infected cases 27-45%

6. AP - Pathophysiology • Autodigestion - primarily due to activation of trypsin • Pancreatic proteases (trypsin, chymotrypsin, elastase, carboxypeptidase and phospholipase A) • secreted as proenzymes • Trypsin is central to this activation and is activated by duodenal brush-border enteropeptidase

7. AP - Pathophysiology Resolution

10. Obstructing Stone in CBD

15. Acute severe upper abdominal pain, 95% Back radiation, 50% Nausea/Vomiting lasting hours Abdominal tenderness, guarding, peritoneal signs Fever Tachycardia Leukocytosis AP - Clinical Presentation

16. AP - Clinical Presentation • Severe pancreatitis • hypotension (fluid sequestration) • SIRS • Cullen sign (periumbilical purpura) • Grey Turner sign (left flank purpura) • hemorrhagic pancreatitis • retroperitoneal hemorrhage

17. AP - Differential Diagnosis • Mesenteric ischemia/infarction • Perforated GU/DU • Intestinal obstruction • Biliary colic • Inferior wall MI • Ectopic pregnancy

18. AP - Diagnosis • THIS IS A CLINICAL DIAGNOSIS • History: Boring epigastric/LUQ • Physical: tenderness, guarding • Labs: CBC, Chemistry, LFT’s, Amylase or Lipase • Plain X-rays: r/o perforated viscous • US: gallstones/ductal dilation/cholecystitis • CT: ONLY to evaluate for severity and complications (normal in 15-30% mild cases) • MRCP: Elevated ALT/AST/Bili/AP and no stones seen on RUQ US.

19. Amylase/Lipase - Dx • Amylase • 3x ULN • 1/2 life 2 h • Increased values secondary to increased release and decreased clearance • Rapid clearance w/i 24h • Biliary > 1000 • Alcohol < 500

20. Lipase - Dx • Lipase • Test of choice for most clinicians • 3x ULN • Better sensitivity/specificity than amylase • Useful early as rise parallels amylase • Useful in delayed presentations secondary to slow clearance • Only from pancreatic origin (ddx includes chronic pancreatitis, pseudocyst, malignancy)

21. Acute Pancreatitis - Dx • Height of amylase and lipase DOES NOT correlate with severity • Once Dx is made, daily measurement of serum amylase has little if any value in assessing the clinical progress of the patient or ultimate prognosis

24. AP - Severity Ranson’s Criteria Risk Factors Mortality <2 <1 % 3-4 16 % 5-6 40% 7-8 ~100%

25. AP - Severity • APACHE-II Severity of Disease • A. Acute physiology Score • B. Age Points • C. Chronic health points • *** Score <8 ---> good prognosis • Various other similar scores including APACHE III

26. <7 = better prognosis

29. Hematocrit and Severity

30. AP - Severity Organ failure is the most important indicator of severity of AP • SIRS • Renal Failure, Cr > 2 mg/dl • GI Bleeding, >500 ml/24 h

32. AP - Treatment • Mild AP • Fluid resuscitation • Careful monitoring • Largely supportive • CT scan generally not helpful in management of mild AP • Most mild AP have interstitial dz

33. AP - Treatment • Severe AP • Contrast CT recommended at some point beyond the first 3 days in severe AP to r/o necrotizing pancreatitis/infection • o/w early CT has not been validated, risk controversial wrt increased microvascular ischemia

34. AP - Treatment • Important Concepts in Managing AP • Recognition of clinically severe AP • Scoring system • Identification of stone disease • ICU management for severe AP • Prompt diagnosis of infected necrosis • Debridement of infected necrosis

37. Definition of Pancreatic Necrosis Diffuse or focal area(s) of non-viable pancreatic parenchyma usually associated with pancreatic fat necrosis. May be sterile or infected.

38. Dx of Infected pancreatic necrosis • Difficult to make clinical diagnosis • fever, leukocytosis, and unresolved organ failure • severe pain seen with both sterile and infected necrosis • CT/US guided FNA procedure of choice • safe • accurate • Gram Stain • 96% sensitivity, 99% specificity

40. Prophylactic Abx • Infection of pancreatic necrosis is primary cause of mortality after 7 days • Prophylactic abx • Most recent Cochrane review (2003) • Decreased mortality (OR 0.32) • Decreased pancreatic sepsis (OR 0.52) • Best studies showed least benefit

41. Prophylactic Abx • On sub-group analysis, imipenem was only abx to show benefit • However, recent RCT showed no benefit with meropenem • No evidence for risk of fungal superinfection • Guidelines have varying opinions • Clearly should only be used in high-risk patients (ie >30% necrosis) for no more than 14 days

43. Nutritional Support • 3 meta-analyses favor enteral over parenteral nutrition • Less sepsis, lower inflammatory markers, much less expensive • Only relevant in severe pancreatitis • Jejunal feeding best-studied, not most practical • Ileus is not a contraindication • Start 3-5 days into course, benefit compared to TPN disappears if started after 7 days • TPN is better than no nutrition

45. Chronic Pancreatitis • Remains a major source of morbidity in US • Admissions average 10 days • Frequent narcotic need • Increased risk of pancreatic ca • Dx usually made after dz is well established • Mortality from complications: 25% at 5 years

46. Chronic Pancreatitis “Continuing inflammatory disease of the pancreas characterized by irreversible morphologic changes that typically cause pain and/or permanent loss of function” • Gastroenterology 2001;120

48. PD Obstruction with Increased PD pressure

50. Etiologies of chronic pancreatitis Cystic fibrosis Hereditary pancreatitis Hypertriglyceridemia Autoimmune Fibrocalcific Other Alcoholic Idiopathic