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

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

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

6. AP - Pathophysiology l Autodigestion - primarily due to activation of trypsin l 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. AP - Clinical Presentation l Acute severe upper abdominal pain, 95% –Back radiation, 50% l Nausea/Vomiting lasting hours l Abdominal tenderness, guarding, peritoneal signs l Fever l Tachycardia l Leukocytosis

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

17. AP - Differential Diagnosis l Mesenteric ischemia/infarction l Perforated GU/DU l Intestinal obstruction l Biliary colic l Inferior wall MI l 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 l 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 l 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. l Height of amylase and lipase DOES NOT correlate with severity l 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 Acute Pancreatitis - Dx

24. AP - Severity Ranson’s Criteria Risk FactorsMortality <2<1 % 3-416 % 5-640% 7-8~100%

25. AP - Severity l APACHE-II Severity of Disease –A. Acute physiology Score –B. Age Points –C. Chronic health points –*** Score 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 l SIRS l Renal Failure, Cr > 2 mg/dl l GI Bleeding, >500 ml/24 h

32. AP - Treatment l 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 l 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 l Important Concepts in Managing AP –Recognition of clinically severe AP l 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 l Difficult to make clinical diagnosis –fever, leukocytosis, and unresolved organ failure – severe pain seen with both sterile and infected necrosis l CT/US guided FNA procedure of choice –safe –accurate – Gram Stain –96% sensitivity, 99% specificity

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

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

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

45. Chronic Pancreatitis l Remains a major source of morbidity in US l Admissions average 10 days l Frequent narcotic need l Increased risk of pancreatic ca l Dx usually made after dz is well established l 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. Cystic fibrosis Hereditary pancreatitis Hypertriglyceridemia Autoimmune Fibrocalcific Cystic fibrosis Hereditary pancreatitis Hypertriglyceridemia Autoimmune Fibrocalcific Alcoholic Idiopathic Other Etiologies of chronic pancreatitis

51. Chronic Pancreatitis l Etiology of CP –ETOH (70%), big duct dz –Idiopathic (20%), small duct dz –Other (10%) l CF l HyperTG (>500) controversial l Tumor l Trauma l Hereditary: both CP and RAP l Pancreas divisum l Congenital anomalies l Tropical: Etiol unclear ?Cassava fruit l Autoimmune (Sjogren’s, PBC, PSC)

52. CP - Dx l Functional abnormalities usually precede structural abnormalities –Up to 30% CP may have normal ERCP but abnormal hormone stimulation test

55. Chronic Pancreatitis Demonstration of some EUS findings in chronic pancreatitis

56. CP - Complications l Diabetes l Steatorrhea l Cyst formation l Jaundice l GI bleeding l Splenic vein thrombosis l Ascites l Pleural and pericaridial effusion l Pancreatic ca l Metastatic fat necrosis l Intramedullary calcification l Pseudoaneurysms Associated diseases l PUD l Carcinoma l Cirrhosis l Peripheral neuropathy l Cardiomyopathy

59. CP - Treatment Goal of treatment - Pain relief - Correction of pancreatic insufficiency -Assess for vitamin deficiencies (B12, folate) - Management of complications

61. CP - Treatment Pancreatic Enzyme Formulations Dosing – before meals (and qhs if experiencing pain) Dose –Viokase, 3-8 tabs each time (NE) –Creon, 3 caps each time (E) (total 30,000 units of lipase) Data very mixed If no improvement --> add adjuvant therapy – sodium bicarbonate, H2B, PPI, MCT’s

62. CP - Treatment l Treatment of Pain –Frustrating!!! 30% placebo rate –Multiple potential etiologies of pain –Narcotic addiction all too common –Celiac/splancnic nerve blocks –Endoscopic treatment –Surgery

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