Chronic pancreatitis – Questions and answers

Transcription

Dr. med. Bruno Strebel
Universitätsklinik für Viszerale Chirurgie und Medizin, Inselspital
Question 1:
Chronic pancreatitis
What is the definition of chronic pancreatitis?
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Question 1:
Chronic pancreatitis has been defined as a continuing inflammatory disease of the
pancreas characterized by irreversible morphologic changes that typically cause pain
and/or permanent loss of function.
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Question 2:
What are the different causes of chronic pancreatitis?
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Question 2:
TIGAR-O
Toxic/Metabolic (Alcohol/Tabacco)
Idiopatic (Tropical calcific pancreatitis)
Genetic (will be discussed later)
Auroimmune (isolated/syndromic i.g. Sjoegren syndrome)
Recurrent and severe (recurrent acute pancreatitis)
Obstructive (pancreas divisum, outflow obstuction)
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Question 3:
Functional testing:
a) Most sensitive test
-
How is it executed?
test characteristics?
b) Most sensitive non invasive test
-
How is it executed?
c) Most applied test
-
How is it executed?
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Question 3:
a) Secretin–pancreozymin test
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Naso-gasric-duodenal tube
Suction of gastric fluid
Testing of duodenal aspirate while applying secretin/CCK or caerulein
Meassurement: bicarbonate concentration over 60 min
Sensitivity 90%, Specificity 94%
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Question 3:
a) 13C-mixed triglyceride breath test (13c-MTG-Test)
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Naso-gasric-duodenal tube
13C-labelled substrate is given orally together with a test meal.
After intra-duodenalhydrolysis of the substrate by specific pancreatic enzymes, 13C-marked
metabolites are released, absorbed from the gut and metabolised within the liver.
As a consequence 13CO2 is released and eliminated with the expired air
A 6-h- recovered 13CO2 below 58% indicates the presence of fat maldigestion with a
sensitivity and specificity higher than 90%
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Question 3:
c) Faecal elastase
-
Pancreatic elastase is highly stable along the GI transit
Single small stool sample by a specific enzymimmunoassay
The oral enzyme substitution therapy does not interfere with the test
not sensitive enough to detect patients with mild chronic pancreatitis, CAVE watery diarrhea
Sensitivity 70% Specificity 85%
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Question 4:
Using imaging technique, the diagnosis of chronic pancreatitis is consistent with
a) A plain abdominal film showing calcifications
b) A native CT-scan schowing calcifications
c) An MRI-scan with beaded appearance of the pancreatic duct, calculi as round filling
defects, and a loss of signal intensity in fat-suppressed T1-weighted images explained
by the fact of pancreatic fibrosis
d) Specific endosonography findings:
Question: What are the EUS criteria for chronic pancreatitis discussed in this paper? And
what are the two Major A criteria?
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Question 4:
The Rosemont Criteria:
GastrointestEndosc2009Jun;69(7):1251-61.
Major A criteria:
- Hyperechoic parenchymal foci with shadowing (calcifications)
- Main pancreatic duct calculi
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Question 4:
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Question 4:
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Question 5:
Hereditary pancreatitis
How is hereditary pancreatitis defined?
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Question 5:
Phenotype HCP is diagnosed when there are
-
recurrent episodes of pancreatitis from childhood
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A positive family history with at least two affected members
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Other causes of pancreatitis have been excluded
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Question 6:
It has become clear over the past several years that the molecular underpinnings of CP are
driven by genetic mutations in the trypsin enzyme cascade
Can you describe this trypsin cascade?
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Question 6:
Trypsinogen
Activatet to
Trypsin
digestive pro-enzymes
catalysis
digestive enzymes
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Question 7:
Which gene is most involved in hereditary pancreatitis?
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Question 7:
Cationic trypsinogen gene (PRSS1)
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Question 8:
Function, kind of mutation and inheritance
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Question 8:
Cationic trypsinogen gene (PRSS1) – 80%
- promotes the expression of trypsinogen
- gain of function mutation
- autosomal dominant
Trypsinogen +++
Activatet to
Trypsin
catalysis
digestive enzymes
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Question 8:
PRSS1-Mutations
Loss of
inhibition
Gain of
activation
Loss of
inhibition
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Question 9:
PRSS1-Mutations
Cationic trypsinogen gene (PRSS1)
- Impact on risk for pancreatic cancer
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Question 9:
PRSS1-Mutations
A cationic trypsinogen gene (PRSS1)-Mutation increases the lifetime risk for pancreatic
cancer by 40%
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Question 10:
Genetic contributors in
idiopathic pancreatitis
What are the 3 most discussed genetic contributors/modifiers in idiopathic pancreatitis?
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Question 10:
1) Pancreatic secretory trypsin inhibitor (SPINK1)
2) Chymotrypsin C (CTRC) – disease modifying
3) Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR)
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Question 10:
Pancreatic secretory trypsin inhibitor (SPINK1) – 20%
- inhibitor of trypsin
- mostly normal function (modifier)
- autosomal recessive
Trypsinogen
Activatet to
Trypsin +++
catalysis
Inhibition missing
digestive enzymes
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Question 10:
Chymotrypsin C (CTRC)
trypsin degradation in the pancreas
loss of function/deletion
autosomal recessive
Trypsinogen
Activatet to
Trypsin +++
catalysis
cleavage missing
digestive enzymes
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Question 10:
Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR):
-
Encodes a c-AMP-activated chloride channel
Responsible for bicarbonate secretion
Bicarbonate accounts for diluting and alkalising the acinair pancreas secretions and prevents
the formation of protein plugs in the ducts
Also autosomale recessive [NEJM 1998] (CF itself is autosomal dominant)
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Question 11:
Autoimmune
pancreatitis
What is the incidence of autoimmune pancreatitis among patients with chronic
pancreatitis?
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Question 11:
Autoimmune
pancreatitis
• The incidence is 2%, data suggest that the number of reported cases of aiP is increasing
with a growing global awareness of this disease
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Question 12:
Autoimmune
pancreatitis
Can you describe the typical patient with autoimmune pancreatitis?
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Question 12:
Autoimmune
pancreatitis
•
Autoimmune pancreatitis mainly occurs in elderly males – in our series the mean age
was 66.5 years (range 25–83 years) and 75% of patients were male. In a US series
by Chari et al. The mean age was 61 years and 85% of patients were male.
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Question 13:
Autoimmune
pancreatitis
What is the typical initial presentation of patients with autoimmune pancreatitis?
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Question 13:
Autoimmune
pancreatitis
• The initial symptom of autoimmune pancreatitis is usually obstructive jaundice induced
by sclerosing cholangitis (74% in our series, 82% in the UK, and 88% in the US).
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Question 14:
Autoimmune
pancreatitis
What is the most specific laboratory test for autoimmune pancreatitis?
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Question 14:
Autoimmune
pancreatitis
• IgG4 levels are closely associated with disease activity. The sensitivity of increased
serum igG4 levels to identify patients with autoimmune pancreatitis was 77% in our
series, 81% in the US and 68% in Korea.
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Question 15:
Autoimmune
pancreatitis
What are the imaging findings of autoimmune pancreatitis?
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Question 15:
Autoimmune
pancreatitis
Imaging in autoimmune pancreatitis:
• Diffuse enlargement of the pancreas and extinction of the lobular contour of the
pancreas are typical findings
• Fibroinflammatory changes involve the peripancreatic adipose tissue, resulting in a
capsulelike rim surrounding the pancreas
• Using diffusion weighted MRI Autoimmune pancreatitis and pancreatic cancer were
detected as high signalintensity areas, but the areas were often diffuse in autoimmune
pancreatitis, while all patients with pancreatic cancer showed solitary areas.
• However, segmental type autoimmune pancreatitis involving one or two parts of the
head, body or tail of the pancreas frequently forms a mass and is sometimes difficult
to differentiate from pancreatic cancer
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Question 16:
Autoimmune
pancreatitis
The specificity for IgG4 in autoimmune pancreatitis is reported as high as 93% (Am J
Gastroenterol. 2007 Aug;102(8):1646-53). Which other important pancreatic disease
has elevated IgG4 levels in up to 4% of cases and why is this important (in respect of
imaginary findings)?
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Question 16:
Autoimmune
pancreatitis
Increased serum igG4 levels is seen in patients with pancreatic cancer in 4%
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Qustion 17:
Autoimmune
pancreatitis
So how is autoimmune pancreatitis diagnosed?
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Question 17:
Autoimmune
pancreatitis
The Japanese ‘Diagnostic Criteria for autoimmune Pancreatitis’ were proposed in 2002 and
revised in 2006:
• Radiological evidence of enlargement of the pancreas and irregular narrowing of the
main pancreatic duct
• Laboratory findings of increased serum gammaglobulin, igG and igG4 levels
• Histological evidence of lymphoplasmacytic infiltration and fibrosis in the pancreas
In 2006, new diagnostic criteria were proposed that included two more factors:
• Response to steroid therapy
• Other organ involvement.
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Qustion 18:
Autoimmune
pancreatitis
So how is autoimmune pancreatitis treated?
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Qustion 18:
Autoimmune
pancreatitis
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•
•
•
Oral prednisolone 0.6 mg/kg daily (about 40mg/d)
Evaluation of the effectiveness of steroid therapy should be performed 2 weeks after its
initiation. a poor response to steroid therapy should raise the possibility of a diagnosis
of pancreatic cancer and the need for reevaluation.
If steroid therapy is effective, the dose should be tapered by 5 mg every 1–2 weeks
until it reaches 15 mg/d.
After this period, the steroid dose should be tapered more gradually to a maintenance
dose over a period of 3–6 months.
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Qustion 19:
Autoimmune
pancreatitis
Are there other IgG4-related sclerosing disease in which IgG4-positive plasma cells and T
lymphocytes extensively infiltrate various organs (autoimmune pancreatitis may be one
manifestation of this disease).
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Qustion 19:
Autoimmune
pancreatitis
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Question 20:
Tropical chronic
pancreatitis
Properties/definition of tropical chronic pancreatitis?
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Question 20
Tropical chronic
pancreatitis
Tropical chronic pancreatitis is a form of ICP which is unique to the tropics. Patients
present at a very young age with recurrent abdominal pain and develop earlier than
other chronic pancreatitis patients diabetes, often before the age of 30 years
(fibrocalculous pancreatic diabetes, FCPD).
SPINK1 – 50%
CTRC – 15%
CFTR – 10%
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Question 21:
Drug-induced
pancreatitis
Which are the three drugs most often involved in drug-induced pancreatitis
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Question 21:
Drug-induced
pancreatitis
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Didanosine (Videx®) – Nukleosid-Reverse-Transkriptase-Inhibitor to treat HIV
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Asparaginase (off the market in CH) – to treat ALL (in children)
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883 cases
177 cases
Azathioprine/Mercaptopurine (Imurek®/Puri-Nethol®) – Immunosuppressant
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170 causes
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Chronic pancreatitis – Questions and answers

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