Dr. med. Bruno Strebel - Mucosal Immunology · - Pancreatic elastase is highly stable along the GI transit ... Questions and answers 9 ... Question: What are the EUS

Chronic pancreatitis – Questions and answers

Dr. med. Bruno Strebel

Universitätsklinik für Viszerale Chirurgie und Medizin, Inselspital

Question 1: Chronic pancreatitis

What is the definition of chronic pancreatitis?

Chronic pancreatitis – Questions and answers 2



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.




What are the different causes of chronic pancreatitis?




TIGAR-O

Toxic/Metabolic (Alcohol/Tabacco)

Idiopatic (Tropical calcific pancreatitis)


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)



Functional testing:

a) Most sensitive test

- How is it executed?

- test characteristics?



b) Most sensitive non invasive test



c) Most applied test





a) Secretin–pancreozymin test

- Naso-gasric-duodenal tube

- Suction of gastric fluid


- Suction of gastric fluid

- Testing of duodenal aspirate while applying secretin/CCK or caerulein

- Meassurement: bicarbonate concentration over 60 min

- Sensitivity 90%, Specificity 94%



a) 13C-mixed triglyceride breath test (13c-MTG-Test)




- 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%



c) Faecal elastase

- Pancreatic elastase is highly stable along the GI transit

- Single small stool sample by a specific enzymimmunoassay


- 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%



Using imaging technique, the diagnosis of chronic pancreatitis is consistent with


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?




The Rosemont Criteria:

GastrointestEndosc2009Jun;69(7):1251-61.

Major A criteria:

- Hyperechoic parenchymal foci with shadowing (calcifications)

- Main pancreatic duct calculi








Question 5: Hereditary pancreatitis

How is hereditary pancreatitis defined?




Phenotype HCP is diagnosed when there are

- recurrent episodes of pancreatitis from childhood


- recurrent episodes of pancreatitis from childhood

- A positive family history with at least two affected members

- Other causes of pancreatitis have been excluded



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?



Trypsinogen

Activatet to


Activatet to

Trypsin

digestive pro-enzymes catalysis digestive enzymes



Which gene is most involved in hereditary pancreatitis?




Cationic trypsinogen gene (PRSS1)




Function, kind of mutation and inheritance




Cationic trypsinogen gene (PRSS1) – 80%

- promotes the expression of trypsinogen

- gain of function mutation

- autosomal dominant Trypsinogen +++


- autosomal dominant Trypsinogen +++

Activatet to

Trypsin



Question 8: PRSS1-Mutations

Loss of inhibition


Gain of activation

Loss of inhibition



Cationic trypsinogen gene (PRSS1)

- Impact on risk for pancreatic cancer




A cationic trypsinogen gene (PRSS1)-Mutation increases the lifetime risk for pancreatic

cancer by 40%


cancer by 40%


Question 10: Genetic contributors inidiopathic pancreatitis

What are the 3 most discussed genetic contributors/modifiers in idiopathic pancreatitis?




1) Pancreatic secretory trypsin inhibitor (SPINK1)

2) Chymotrypsin C (CTRC) – disease modifying


2) Chymotrypsin C (CTRC) – disease modifying

3) Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR)



Pancreatic secretory trypsin inhibitor (SPINK1) – 20%

- inhibitor of trypsin

- mostly normal function (modifier)

- autosomal recessive Trypsinogen


- autosomal recessive Trypsinogen

Activatet to

Trypsin +++ Inhibition missing




Chymotrypsin C (CTRC)

trypsin degradation in the pancreas

loss of function/deletion

autosomal recessive Trypsinogen


autosomal recessive Trypsinogen

Activatet to

Trypsin +++ cleavage missing




Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR):

- Encodes a c-AMP-activated chloride channel


- 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)


Question 11: Autoimmunepancreatitis

What is the incidence of autoimmune pancreatitis among patients with chronic

pancreatitis?


pancreatitis?


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


with a growing global awareness of this disease


Question 12:Autoimmunepancreatitis

Can you describe the typical patient with 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.


by Chari et al. The mean age was 61 years and 85% of patients were male.



What is the typical initial presentation of patients with 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).


by sclerosing cholangitis (74% in our series, 82% in the UK, and 88% in the US).



What is the most specific laboratory test for 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


serum igG4 levels to identify patients with autoimmune pancreatitis was 77% in our

series, 81% in the US and 68% in Korea.



What are the imaging findings of autoimmune pancreatitis?




Imaging in autoimmune pancreatitis:

• Diffuse enlargement of the pancreas and extinction of the lobular contour of the

pancreas are typical findings


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



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


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)?



Increased serum igG4 levels is seen in patients with pancreatic cancer in 4%



Qustion 17:Autoimmunepancreatitis

So how is autoimmune pancreatitis diagnosed?




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


• 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.



So how is autoimmune pancreatitis treated?




• 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


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.



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).


manifestation of this disease).





Question 20:Tropical chronicpancreatitis

Properties/definition of tropical chronic pancreatitis?



Question 20Tropical chronicpancreatitis

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


other chronic pancreatitis patients diabetes, often before the age of 30 years

(fibrocalculous pancreatic diabetes, FCPD).

SPINK1 – 50%

CTRC – 15%

CFTR – 10%


Question 21:Drug-inducedpancreatitis

Which are the three drugs most often involved in drug-induced pancreatitis



Question 21:Drug-inducedpancreatitis

- Didanosine (Videx®) – Nukleosid-Reverse-Transkriptase-Inhibitor to treat HIV

- 883 cases


- Asparaginase (off the market in CH) – to treat ALL (in children)- 177 cases

- Azathioprine/Mercaptopurine (Imurek®/Puri-Nethol®) – Immunosuppressant- 170 causes

Documents

Dr. med. Bruno Strebel - Mucosal Immunology · - Pancreatic elastase is highly stable along the GI transit ... Questions and answers 9 ... Question: What are the EUS