Chronic pancreatitis Questions and answers. Dr. med. Bruno Strebel
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1 Chronic pancreatitis Questions and answers Dr. med. Bruno Strebel
2 Question 1: Chronic pancreatitis What is the definition of chronic pancreatitis? Chronic pancreatitis Questions and answers 2
3 Question 1: Chronic pancreatitis 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. Chronic pancreatitis Questions and answers 3
4 Question 2: Chronic pancreatitis What are the different causes of chronic pancreatitis? Chronic pancreatitis Questions and answers 4
5 Question 2: Chronic pancreatitis 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) Chronic pancreatitis Questions and answers 5
6 Question 3: Chronic pancreatitis Functional testing: a) Most sensitive test - How is it executed? - test characteristics? b) Most sensitive non invasive test - How is it executed? - test characteristics? c) Most applied test - How is it executed? - test characteristics? Chronic pancreatitis Questions and answers 6
7 Question 3: Chronic pancreatitis a) Secretin pancreozymin test - 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% Chronic pancreatitis Questions and answers 7
8 Question 3: Chronic pancreatitis a) 13C-mixed triglyceride breath test (13c-MTG-Test) - 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% Chronic pancreatitis Questions and answers 8
9 Question 3: Chronic pancreatitis 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% Chronic pancreatitis Questions and answers 9
10 Question 4: Chronic pancreatitis 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? Chronic pancreatitis Questions and answers 10
11 Question 4: Chronic pancreatitis The Rosemont Criteria: GastrointestEndosc2009Jun;69(7): Major A criteria: - Hyperechoic parenchymal foci with shadowing (calcifications) - Main pancreatic duct calculi Chronic pancreatitis Questions and answers 11
12 Question 4: Chronic pancreatitis Chronic pancreatitis Questions and answers 12
13 Question 4: Chronic pancreatitis Chronic pancreatitis Questions and answers 13
14 Question 5: Hereditary pancreatitis How is hereditary pancreatitis defined? Chronic pancreatitis Questions and answers 14
15 Question 5: Hereditary pancreatitis Phenotype HCP is diagnosed when there are - recurrent episodes of pancreatitis from childhood - A positive family history with at least two affected members - Other causes of pancreatitis have been excluded Chronic pancreatitis Questions and answers 15
16 Question 6: Hereditary pancreatitis 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? Chronic pancreatitis Questions and answers 16
17 Question 6: Hereditary pancreatitis Trypsinogen Activatet to Trypsin digestive pro-enzymes catalysis digestive enzymes Chronic pancreatitis Questions and answers 17
18 Question 7: Hereditary pancreatitis Which gene is most involved in hereditary pancreatitis? Chronic pancreatitis Questions and answers 18
19 Question 7: Hereditary pancreatitis Cationic trypsinogen gene (PRSS1) Chronic pancreatitis Questions and answers 19
20 Question 8: Hereditary pancreatitis Function, kind of mutation and inheritance Chronic pancreatitis Questions and answers 20
21 Question 8: Hereditary pancreatitis Cationic trypsinogen gene (PRSS1) 80% - promotes the expression of trypsinogen - gain of function mutation - autosomal dominant Trypsinogen +++ Activatet to Trypsin digestive pro-enzymes catalysis digestive enzymes Chronic pancreatitis Questions and answers 21
22 Question 8: PRSS1-Mutations Loss of inhibition Gain of activation Loss of inhibition Chronic pancreatitis Questions and answers 22
23 Question 9: PRSS1-Mutations Cationic trypsinogen gene (PRSS1) - Impact on risk for pancreatic cancer Chronic pancreatitis Questions and answers 23
24 Question 9: PRSS1-Mutations A cationic trypsinogen gene (PRSS1)-Mutation increases the lifetime risk for pancreatic cancer by 40% Chronic pancreatitis Questions and answers 24
25 Question 10: Genetic contributors in idiopathic pancreatitis What are the 3 most discussed genetic contributors/modifiers in idiopathic pancreatitis? Chronic pancreatitis Questions and answers 25
26 Question 10: Genetic contributors in idiopathic pancreatitis 1) Pancreatic secretory trypsin inhibitor (SPINK1) 2) Chymotrypsin C (CTRC) disease modifying 3) Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) Chronic pancreatitis Questions and answers 26
27 Question 10: Genetic contributors in idiopathic pancreatitis Pancreatic secretory trypsin inhibitor (SPINK1) 20% - inhibitor of trypsin - mostly normal function (modifier) - autosomal recessive Trypsinogen Activatet to Trypsin +++ Inhibition missing digestive pro-enzymes catalysis digestive enzymes Chronic pancreatitis Questions and answers 27
28 Question 10: Genetic contributors in idiopathic pancreatitis Chymotrypsin C (CTRC) trypsin degradation in the pancreas loss of function/deletion autosomal recessive Trypsinogen Activatet to Trypsin +++ cleavage missing digestive pro-enzymes catalysis digestive enzymes Chronic pancreatitis Questions and answers 28
29 Question 10: Genetic contributors in idiopathic pancreatitis 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) Chronic pancreatitis Questions and answers 29
30 Question 11: Autoimmune pancreatitis What is the incidence of autoimmune pancreatitis among patients with chronic pancreatitis? Chronic pancreatitis Questions and answers 30
31 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 Chronic pancreatitis Questions and answers 31
32 Question 12: Autoimmune pancreatitis Can you describe the typical patient with autoimmune pancreatitis? Chronic pancreatitis Questions and answers 32
33 Question 12: Autoimmune pancreatitis Autoimmune pancreatitis mainly occurs in elderly males in our series the mean age was 66.5 years (range 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. Chronic pancreatitis Questions and answers 33
34 Question 13: Autoimmune pancreatitis What is the typical initial presentation of patients with autoimmune pancreatitis? Chronic pancreatitis Questions and answers 34
35 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). Chronic pancreatitis Questions and answers 35
36 Question 14: Autoimmune pancreatitis What is the most specific laboratory test for autoimmune pancreatitis? Chronic pancreatitis Questions and answers 36
37 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. Chronic pancreatitis Questions and answers 37
38 Question 15: Autoimmune pancreatitis What are the imaging findings of autoimmune pancreatitis? Chronic pancreatitis Questions and answers 38
39 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 Chronic pancreatitis Questions and answers 39
40 Question 16: Autoimmune pancreatitis The specificity for IgG4 in autoimmune pancreatitis is reported as high as 93% (Am J Gastroenterol Aug;102(8): ). 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)? Chronic pancreatitis Questions and answers 40
41 Question 16: Autoimmune pancreatitis Increased serum igg4 levels is seen in patients with pancreatic cancer in 4% Chronic pancreatitis Questions and answers 41
42 Qustion 17: Autoimmune pancreatitis So how is autoimmune pancreatitis diagnosed? Chronic pancreatitis Questions and answers 42
43 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. Chronic pancreatitis Questions and answers 43
44 Qustion 18: Autoimmune pancreatitis So how is autoimmune pancreatitis treated? Chronic pancreatitis Questions and answers 44
45 Qustion 18: Autoimmune pancreatitis 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. Chronic pancreatitis Questions and answers 45
46 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). Chronic pancreatitis Questions and answers 46
47 Qustion 19: Autoimmune pancreatitis Chronic pancreatitis Questions and answers 47
48 Question 20: Tropical chronic pancreatitis Properties/definition of tropical chronic pancreatitis? Chronic pancreatitis Questions and answers 48
49 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% Chronic pancreatitis Questions and answers 49
50 Question 21: Drug-induced pancreatitis Which are the three drugs most often involved in drug-induced pancreatitis Chronic pancreatitis Questions and answers 50
51 Question 21: Drug-induced pancreatitis - Didanosine (Videx ) Nukleosid-Reverse-Transkriptase-Inhibitor to treat HIV cases - Asparaginase (off the market in CH) to treat ALL (in children) cases - Azathioprine/Mercaptopurine (Imurek /Puri-Nethol ) Immunosuppressant causes Chronic pancreatitis Questions and answers 51
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