Transcript 11- pancreas pathology Lect.(1)

The Pancreas
Outline
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Introduction
Congenital anomalies
Anatomy
Acute pancreatitis
Pancreatic pseudo
cysts
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Chronic pancreatitis
Complications
Pancreatic neoplasm
Pancreatic cancers
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.
Anatomy – Ductal system
Congenital anomalies
Several anatomical variants. Most are not
clinically significant.
• Pancreatic divisum
=>most common clinically(incidence is 310%)
=>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
© 2005 Elsevier
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.
Pancreatic Acinar
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24year old obese woman presents with
sudden onset epigastric pain radiating to the
back. She neither smokes nor drink.
Laboratory tests shows elevated levels of
lipase and amylase.
Q1 ..The most likely diagnosis is ?
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Q2 The most likely risk factor is?
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Acute Pancreatitis
• Inflammation of Pancreas
• Potentially reversible
• Acute alcohol ingestion /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
What is/are the leading cause(s)
of Acute pancreatitis?
GET SMASHED
• G all stones
• E thanol
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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)
• Hereditary: PRSS 1 Mutation, SPINK 1
mutation,
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
Acute Pancreatitis
Acute Pancreatitis
• Morphology:
Variable picture;
Basic alterations are:
Micro vascular leakage, Fat necrosis, Acute
inflammation, destruction of parenchyma,
Destruction of blood vessels and
hemorrhage.
Fat necrosis may occur as result of
enzymatic digestion of adipocytes by
Lipase to yield fatty acids which combine
with calcium to form calcium salts.
Clinical Presentation
• Pain - “steady, dull”- epigastric/upper
quadrant, radiation to the back, Left
shoulder.
– Commonly worse on supine position
– No peritoneal sign - since
retroperitoneal location
• Nausea/Vomitting
• Fever
Clinical Presentation
• Hypotension/Shock (30~40%)
– Plasma exudation to retroperitoneal
space
– Increased peripheral vascular
permeability
– Hemorrhage
– Vomiting
– Peripheral vasodilatation
Cutaneous signs of
hemorrhagic pancreatitis
Grey Turner Sign
Cullen Sign
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
Labs
• Serum amylase
– Rises in 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%
Imaging Studies
• ERCP (Endoscopic
Retrograde
CholangioPancreatography)
– Diagnosis - Confirm
presence of common
duct stones
– Therapy - Removal of
common bile duct
stone in severe
pancreatitis patients
Acute Pancreatitis-Outcome
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Peritonitis
Pseudocysts
Abscesses
Chronic pancreatitis
Diabetes
mellitus(rare)
Prognostic Indicators
• Ranson’s Criteria:
– Original Criteria for classification of
pancreatitis
Ranson’s Criteria
Assessment of Severity in Acute Pancreatitis
Ranson’s Criteria
• < 3 signs = excellent prognosis
• 3~5 signs = 10 – 20% mortality
 6 signs = > 50% mortality
• General rule:  3 signs  Severe
Pancreatitis
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.
• Frequently complicates acute
pancreatitis may also occur in chronic
pancreatitits and Trauma.
• Death is caused by secondary
infection, hemorrhage, or rupture.
Chronic Pancreatitis
Definition
• A persistent inflammatory disease of
the pancreas
– Irreversible morphologic changes
– Typically causing pain and/or loss of
digestive function
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.
Chronic Pancreatitis
• Gross
– Fibrotic & firm
– Pancreatic duct
• Dilated
• Stones
– Constriction
• Common bile duct
• Duodenum
• Pyloris
Chronic Pancreatitis
• Histology
– Fibrosis
– Scattered foci of
chronic inflammation
– Ducts & islets of
Langerhans persist
– Calcifications
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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
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)
Chronic pancreatitis
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
Complications of Chronic
Pancreatitis
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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
Serine protease inhibitor Kasal type 1,(Spink 1):
codes for a secretory trypsin inhibitor.
 Mutation leads uncontrolled activation of Trypsin.
 Autosomoal recessive.
PRSS1:Cationic trypsinogen gene, Normally
 responsible for inactivation of trypsin by another
trypsin molecule. Mutation leads to resistant
trypsin molecule.
 Autosomal dominant
 The two conditions can lead to :Acute,chronic
pancreatitis as well as pancreatic CA.
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
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
PANCREATIC CANCER
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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
Familial syndromes:
 Peutz-Jeghers
 Hereditary Pancreatitis(PRSSI mutation, pink 1)
 Familial atypical multiple mole melanoma
syndrome, FAMMM(p16)
 Hereditary breast and ovarian cancer (BRCA2)
 Hereditary non polyposis colorectal cancer Lynch
II,(hMSH2)
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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
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Anatomical Prevalence
• Head of Pancreas: ~70% of the
cases, presenting as jaundice or
pancreatic insufficiency
CBD
PD
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Ductal adenocarcinomas
Often poorly differentiated
Highly invasive
Desmoplasia
Poorly formed glands in a densely fibrotic
stroma on histology.
FREQUENT
abdominal pain;
anorexia and weight loss;
jaundice (lesions of pancreatic head only);
INFREQUENT
glucose intolerance;
migratory thrombophlebitis (Trousseau’ sign);
gastrointestinal hemorrhage;
*splenomegaly
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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
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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
Poor prognosis.