1. The Pancreas 1 1

2. Outline Introduction Congenital anomalies Anatomy Acute pancreatitis
Pancreatic pseudo cysts
Chronic pancreatitis
Complications
Pancreatic neoplasm
Pancreatic cancers 2

3. Introduction Complex lobulated organ Retro-peritoneal
Exocrine and endocrine portion(digestive enzyme and hormones respectively)
Endocrine pancreas :less than 1% of pancreas. Secretes insulin, somatostatin and glucagon.(discussed in endocrinology)
Disorders of exocrine Pancreas includes:
Congenital ,Acute/Chronic Pancreatitis, Neoplasm and Cystic fibrosis. 3

4. Congenital anomalies
Several anatomical variants. Most are not clinically significant.
Pancreatic divisum
=>most common clinically(incidence is 3-10%)
=>Failure of fusion of the dorsal pancreatic primordium with the ventral primordium.
=>the bulk of the pancreas drains through the minor sphincter
=>Predisposes to chronic pancreatitis
The other congenital anomalies are very rare
Agenesis (usually incompatible with life)
Annular pancreas – abnormal fusion =>duodenal obstruction
Ectopic pancreas – stomach, duodenum, jejunum, ileum and meckel diverticulum.- inflammation and mucosal bleeds. 4 4

5. Anatomy – Ductal system5 5

6. Pancreatic Acinar 6

7. Acute Pancreatitis Inflammation of Pancreas Potentially reversible
Acute alcohol/Gallstone are the leading cause.
Common, incidence 10/20 cases per 100,000
>200,000 admissions/yr in U.S.
Mostly mild
~10% complicated and severe
~10,000 deaths/year 7 7

8. What is the leading cause of Acute pancreatitis?

9. GET SMASHED G all stones E thanol T rauma S teroids
M umps, mycoplasma and coxsakiae
A utoimmune
S corpions
H yperlipidaemia, hypercalcemia
E RCP
D rugs (thiazide diuretics, azathioprine, procainamide, frusemide, estrogens, methyl dopa) 9 9

10. Mechanisms of Acute Pancreatitis
Etiology dependent
No established pathogenesis
Three widely accepted pathways:
- Pancreatic duct obstruction
- Primary Acinar cell injury
-Defective transport of Pro-enzymes 10 10

11. 11

12. Acute Pancreatitis 12 12

13. Acute Pancreatitis Morphology: Variable picture;
from Mild inflammation and edema to severe necrosis of the parenchyma and hemorhage. 13 13

14. Clinical Presentation
Pain - “steady, dull”- epigastric/upper quadrant, radiation to the back
Commonly worse on supine position
No peritoneal sign - since retroperitoneal location
Nausea/Vomitting
Fever 14 14

15. Clinical Presentation
Hypotension/Shock (30~40%)
Plasma exudation to retroperitoneal space
Increased peripheral vascular permeability
Hemorrhage
Vomiting
Peripheral vasodilatation 15 15

16. Cutaneous signs of hemorrhagic pancreatitis
Grey Turner Sign
Cullen Sign 16 16

17. Labs
Serum amylase
Rises in AP 2~12hrs after onset and stays up for 3~5 days
The magnitude of elevation is not related to prognosis
Sensitivity=80~90% ,Specificity=70%
Serum lipase
Tends to be elevated several days longer than amylase levels
Sensitivity=87% Specificity=90%
Serum amylase & lipase:
Sensitivity=95%
Specificity=90% 17 17

18. Diagnostic Testing: Imaging Studies
CXR/Plain abdominal films – dilated bowel loops
CT scan – diagnosis, predict outcome/prognosis
Abdominal Ultrasound – detects stone ( in gallbladder & bile duct)
May be difficult to evaluate pancreas in up to 30% of cases due to overlying bowel gas 18 18

19. Imaging Studies
ERCP (Endoscopic Retrograde Cholangio- Pancreatography)
Diagnosis - Confirm presence of common duct stones
Therapy - Removal of common bile duct stone in severe pancreatitis patients 19 19

20. Acute Pancreatitis-Outcome
Peritonitis
Pseudocysts
Abscesses
Chronic pancreatitis
Diabetes mellitus(rare) 20 20

21. Prognostic Indicators
Ranson’s Criteria:
Original Criteria for classification of pancreatitis 21 21

22. Ranson’s Criteria
Assessment of Severity in Acute Pancreatitis 22 22

23. Ranson’s Criteria < 3 signs = excellent prognosis
3~5 signs = 10 – 20% mortality
 6 signs = > 50% mortality
General rule:  3 signs  Severe Pancreatitis 23 23

24. Pancreatic Pseudocysts
Collection of enzyme-rich pancreatic fluid and tissue debris arising within areas of necrosis or an obstructed smaller duct.
It is not surrounded by a true capsule.
Death is caused by secondary infection, hemorrhage, or rupture. 24 24

25. 25

26. Chronic Pancreatitis 26 26

27. Definition A persistent inflammatory disease of the pancreas
Irreversible morphologic changes
Typically causing pain and/or loss of digestive function 27 27

28. Etiologies of Chronic Pancreatitis
Alcohol (~70% of CP)
Hereditary-Genetic mutation.
=> PRSSI
=>Spink1
Obstruction
Trauma
Pancreas divisum
Tropical
Hyperparathyroidism
Idiopathic-40% truly idiopathic. Most are due to hereditary causes.
-CFTR mutations(cystic Fibrosis) is cause of Idiopathic chronic pancreatitis. 28 28

29. Chronic Pancreatitis Gross Fibrotic & firm Pancreatic duct
Dilated
Stones
Constriction
Common bile duct
Duodenum
Pyloris 29 29

30. Chronic Pancreatitis Histology Fibrosis
Scattered foci of chronic inflammation
Ducts & islets of Langerhans persist
Calcifications 30 30

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32. Clinical Presentation
Abdominal pain - primary feature
Weight loss
15 – 25% CP may be painless
Malabsorption/steatorrhea – usually occurs when enzyme secretion < 10% of normal
Diabetes (usually a late finding) 32 32

33. Diagnosis Frequently made by history alone
e.g. an alcoholic with recurrent attacks
Plain abdominal X-ray - calcification in ~30%
diagnostic in clinically suspected patients
Serum amylase & lipase
usually elevated - can be normal 33 33

34. Chronic pancreatitis 34 34

35. Imaging
abdominal ultrasound or CT (shows abnormalities in size and consistency of the pancreas, pancreatic pseudocyst, or dilated pancreatic ducts.
ERCP shows abnormalities of the main pancreatic duct and secondary branches 35 35

36. Complications of Chronic Pancreatitis
Pseudocyst
Pancreatic ascites
Pancreatic fistula
Weight loss/ malabsorption
Pancreatic carcinoma -40%lifetime risk of pancreatic CA in those with hereditary pancreatitis
Role of chronic pancreatitis in pancreatic CA is otherwise inconclusive.
Common bile duct obstruction
Splenic /portal vein thrombosis 36 36

37. Cystic neoplasm 5-15% of pancreatic cysts are neoplastic
Most cysts in the pancreas are pseudodocysts
Three common types of neoplastic cysts.
Serous - Benign, more in females
Mucinous (always in females)
Intraductal papillary mucinous neoplasms
(IPMN)..more in males
Both Mucinous and IPMN could present as:benign,borderline or malignant tumors 37 37

38. Pancreatic Cancer 31,800 new cases, 31,200 deaths in 2004 U.S.
5-yr Survival Rate: <4%
~10-20% resectable at diagnosis
Difficult to treat by ChemoXRT due to its highly resistant nature
4th cause of cancer related death 38 38

39. PANCREATIC CANCER ETIOLOGY. I. poorly characterized
60-80 yrs,Blacks>whites, Increased risk in Jews
cigarette smoking (2-3 times)-
Smoking is the most significant environmental risk factor
Association with:
chronic pancreatitis; causal relationship established with hereditary forms only.
long-standing D/M.(not clear whether cause or consequences since ca pancreas could cause D/M)
No correlation with:
Alcohol and coffee abuse
Cholelithiasis 39 39

40. Pancreatic Cancer Etiology II.
Familial syndromes:
Peutz-Jeghers
Hereditary Pancreatitis(PRSSI mutation)
Familial atypical multiple mole melanoma syndrome,FAMMM(p16)
Hereditary breast and ovarian cancer (BRCA2)
Hereditary non polyposis colorectal cancer Lynch II,(hMSH2)

41. Molecular Carcinogenesis
Pancreatic intraepithelial neoplasm ,PanIN,is the putative precursor lesion
Telomere shortening in PanINs leads to accumulation of progressive chromosomal abnormalities.
K-RAS oncogene is activated,while the tumor suppressor genes ( P53, P16,SMAD4).are inactivated.
SMAD4 appears to be the more specific tumor suppressor gene involved

42. Figure 17-8 Model for the development of pancreatic cancer
Figure 17-8 Model for the development of pancreatic cancer. It is postulated that telomere shortening, and mutations of the oncogene K-RAS occur at early stages, inactivation of the p16 tumor suppressor gene occurs at intermediate stages, and the inactivation of the p53, SMAD4, and BRCA2 tumor suppressor genes occurs at late stages. Note that while there is a general temporal sequence of changes, the accumulation of multiple mutations is more important than their occurrence in a specific order. (Adapted from Wilentz RE, et al.: Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res 60:2002, 2000.)
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43. Anatomical Prevalence
Head of Pancreas: ~70% of the cases, presenting as jaundice or pancreatic insufficiency
CBD PD 43 43

44. Morphology and Histology
Ductal adenocarcinomas
Often poorly differentiated
Highly invasive
Desmoplasia
Poorly formed glands in a densely fibrotic stroma on histology.

46. PRESENTING SIGNS AND SYMPTOMS OF PANCREATIC CARCINOMA
FREQUENT
abdominal pain;
anorexia and weight loss;
jaundice (lesions of pancreatic head only);
INFREQUENT
glucose intolerance;
palpable gallbladder with painless jaundice (Courvoisier's sign);
migratory thrombophlebitis (Trousseau’ sign);
gastrointestinal hemorrhage;
*splenomegaly

47. Diagnosis No effective screening
Imaging studies,CT are good for diagnosis and prognosis
CA 19-9, carcinoembryonic antigen, are tumor markers but unreliable;lack specificity
Poor prognosis

48. Progression
Adenocarcinomas appear at the mean age of 55 yr and occur 1.5 to 2 times more often in men.
locally invasive
Direct invasion of retroperitoneal structures,
spread to regional lymph nodes,
Distant Metastasis