Chronic Pancreatitis Flashcards
definition
> > persistent inflammation and irreversible fibrosis associated with atrophy of the pancreatic parenchyma
> > associated with chronic pain and endocrine and exocrine insufficiency
MC cause and others
> > heavy alcohol consumption is the most common cause of chronic pancreatitis
> > chronic duct obstruction
trauma
divisum
cystic dystrophy of the duodenal wall
hyperparathyroidism
hypertriglyceridemia
autoimmune pancreatitis
tropical pancreatitis
hereditary pancreatitis
In up to 20% of patients, Idiopathic.
How does Alcohol cause chronic pancreatitis ?
- increases the total protein concentration in the pancreatic juice
- it promotes the synthesis and secretion of lithostathine
- it increases glycoprotein 2 secretion
- formation of protein plugs and eventually stones inside the pancreatic duct.
- predisposed to autodigestion
- fatty acid ethyl esters and reactive oxygen species, cause fragility of intraacinar organelles, such as zymogen granules and lysosomes,
- Acetaldehyde > direct injury
- enhanced NF-κB activity, intracellular calcium levels.
Response of Pancreatic stellate cells (PSCs)
> > specialized quiescent fibroblasts found at the base of acinar cells
differentiate into activated myofibroblasts
Examples of these proteins include collagen I and III, fibronectin, laminin, and matrix metalloproteinases.
chronic necrosis and inflammation (necroinflammation) induce the release of inflammatory mediators, such as platelet-derived growth factor, TGF-β, TNF-α, IL-1, and IL-6, which are known to activate PSCs.
> > chronic necroinflammation induced by ethanol activates PSCs and induces pancreatic fibrosis.
smoking Role ?
Increases the Risk
> > risk of pancreatic calcifications and diabetes mellitus is increased in patients who smoke
PRSS1 Gene
Mutations in the cationic trypsinogen gene, also known as protease serine 1 (PRSS1) gene
> > are common in hereditary chronic pancreatitis.
PRSS1 is located on chromosome 7 and regulates trypsinogen production
mutations in this gene are associated with intraacinar trypsinogen activation.
SPINK-1
> > SPINK-1 is a peptide secreted by acinar cells that regulates the premature activation of trypsinogen
> > they lower the threshold for chronic pancraetitis development and influence the severity of the disease.
> > SPINK1 mutations are more prevalent in alcoholic, hereditary, and idiopathic pancreatitis.
CFTR Gene
> > affect the normal secretion of bicarbonate, decrease pancreatic juice volume, and augment the concentration of pancreatic enzymes inside the pancreatic duct.
> > Homozygous CFTR mutations result in cystic fibrosis;
> > heterozygous mild mutations predispose to pancreatic exocrine insufficiency and chronic pancreatitis.
> > higher in patients with alcoholic, idiopathic, and hereditary pancreatitis
chymotrypsin C gene
> > chymotrypsin C protects against pancreatitis by degrading trypsinogen
Autoimmune Pancreatitis
> > Type 1, which is the pancreatic manifestation of an immunoglobulin G4-related disease
> > Type 2, a pancreatic specific disorder, not associated with immunoglobulin G4.
> > closely mimicking patients with pancreatic adenocarcinoma.
Type 1
> > Type 1 is the most common
> > it is characterized by dense, periductal lymphoplasmacytic infiltrates, storiform fibrosis, and obliterative venulitis
> > Plasmatic cells typically stain positive for immunoglobulin G4.
Type 2
> > the pancreas is infiltrated by neutrophils, lymphocytes, and plasma cells
Tropical Pancreatitis
> > particularly in India
> > associated with cassava ingestion and SPINK1 mutations
What Percentage of Gland needs to be dysfunctional before steatorrhea, diarrhea, and other symptoms of malabsorption develop
> > At least 90% of the gland needs to be dysfunctional before steatorrhea, diarrhea, and other symptoms of malabsorption develop
In severe cases, what they will have ?
> > diseases associated with fat-soluble vitamin deficiency, such as bleeding, osteopenia, and osteoporosis, develop
When will Diabetes Occur
> > 40% to 80% of patients will have clinical manifestations of diabetes mellitus, typically occurring years after the onset of abdominal pain and pancreatic exocrine insufficiency.
Complications of Chronic pancreatitis ?
> > Jaundice or cholangitis occurs in 5% to 10% of patients because of fibrosis of the distal common bile duct.
> > obstruct the duodenum, leading to severe nausea, vomiting, and abdominal pain.
The most common CT findings in chronic pancreatitis include
> > dilated pancreatic duct (68%)
parenchymal atrophy (54%)
pancreatic calcifications (50%)
Role of MRI
> > Alternative to CT
The sensitivity for the diagnosis of pancreatic calcifications is lower
MRCP with secretin injection is particularly useful to evaluate intraductal strictures and pancreatic duct disruption.
ERCP ?
- If CT and MRI Contraindicated or didnt Diagnose
- Therapeutic for :
» stricture, stone, pseudocysts, and biliary stenosis.
EUS ?
> > most accurate technique to diagnose chronic pancreatitis in patients with minimal change disease or in the early stages
> > Histologic evidence of inflammation, atrophy, and fibrosis is the gold standard for the diagnosis of chronic pancreatitis
Rosemont consensus-based endoscopic ultrasound features for diagnosis of chronic pancreatitis.
Parenchymal Features
» Major A Criteria
* Hyperechoic foci with postacoustic shadowing
> > Major B Criteria
* Honeycombing lobularity
> > Minor Criteria
* Hyperechoic, nonshadowing foci ≥3 mm in length and width
* Lobularity including three or more noncontiguous lobules in the body or tail
* Pancreatic cysts ≥2 mm in short axis
* At least three strands
Rosemont consensus-based endoscopic ultrasound features for diagnosis of chronic pancreatitis.
Ductal Features
» Major A Criteria
* Main pancreatic duct calculi
> > Minor Criteria
* Irregular main pancreatic duct contour
* Dilated side branches
* Main pancreatic duct dilation (≥3.5 mm in the body or ≥1.5 mm in the tail)
* Hyperechoic main pancreatic duct margin >50% of the main pancreatic duct in the body and tail
Functional Tests
> > fecal elastase 1 level is the preferred noninvasive study to diagnose pancreatic exocrine insufficiency.
> > using monoclonal or polyclonal anti–human elastase 1 antibodies
> > fecal elastase 1 concentration between 100 and 200 μg/g defines mild to moderate pancreatic insufficiency;
> > fecal elastase 1 concentration below 100 μg/g establishes the diagnosis of severe pancreatic exocrine insufficiency.
Another Functional Test
> > The fecal fat and weight estimation test measures the stool content of fat after a nutritional fat intake of 100 g/day for 3 days.
> > If the stool fat content exceeds 7 g/day, the diagnosis of steatorrhea is established
Medical Tx
-Palliation of Symptoms
-multidisciplinary team
-Stop Drinking and Smoking
-Diet ( Low Fat Diet )
-Treat Hypertriglyceridemia
Pain management
> > Nonsteroidal antiinflammatory drugs are the first line of treatment. Moderate to severe pain
if no response treated with tramadol.
If no response potent long-acting narcotics
Alternative drugs :
tricyclic antidepressants
selective serotonin reuptake inhibitors
combined serotonin and norepinephrine reuptake inhibitors, gabapentin, and α2δ inhibitors
Celiac neurolysis
Pancreatic Exocrine Insufficiency
Pancretic Enzyme Replacement
90,000 USP Lipase to avoid malabsorbtion
Given atleast 6 weeks
With PPIs to improve Effect
Endocrine Insufficiency
> > deficiency of insulin and other regulatory hormones such as glucagon.
> > These patients are at higher risk of suboptimal glucose control; particularly severe hypoglycemia related to insulin
Interventional Therapy: Endoscopic Treatment
> > ERCP is the primary modality for treating symptomatic pancreatic duct obstruction with dilation and polyethylene stent placement
> > After Ruling Out Malignant Disease by CT, MRI or EUS
> > Endoscopic stone extraction should be considered for patients with pain and pancreatic duct dilation secondary to stones.
Extracorporeal shock wave lithotripsy followed by therapeutic ERCP
pancreatic duct stenting may benefit patients by relieving obstruction
How to treat Biliary Obstruction
> > Biliary obstruction caused by chronic pancreatitis occurs in 10% of patients and is best treated with surgical bypass.
> > Temporary relief of the obstruction with plastic stents is indicated for patients with cholangitis or for those who are severely malnourished.
Resection vs decompression Surgery
> > dilated pancreatic duct (defined as diameter >7 mm), or large duct disease, require a decompressing procedure
> > patients with a nondilated pancreatic duct, or small duct disease, require a resectional procedure.
What sign seen on MRCP represent Stenosis and dilatation
> > chain of lakes, which reflects the presence of multiple dilations and stenoses.
treatment of pancreatic duct dilatation
> > side-to-side Roux-en-Y pancreaticojejunostomy, also known as the modified Puestow procedure or lateral pancreaticojejunostomy.
modified Puestow procedure or lateral pancreaticojejunostomy.
> > anterior surface of the pancreatic duct is opened
frozen Section to rule out Cancer
proximal extent of tissue resection is within 1 cm of the duodenum, and the distal limit is within 1 cm to 2 cm of the end of the pancreas
Extract all stones
Then Roux en Y lateral pancreaticojejunostomy
Advantage and Disadvantage of Modified Puestow
> > main advantage:
parenchymal conservation, which preserves endocrine and exocrine function.
> > 30% of cases will recur
Will not stop the Progression
factors associated with recurrence
> > smoking and alcohol ingestion after surgery
failure to decompress the head and uncinate process properly
length of the pancreaticojejunostomy
Frey procedure
> > anterior surface of the pancreatic duct has been completely exposed
the anterior portion of the head of the pancreas is also resected, leaving a 1-cm rim of pancreatic tissue along the duodenal margin.
Indications for Frey
> > dilated pancreatic duct secondary to a benign stricture in the head of the pancreas associated with severe inflammation, scarring, or portal hypertension surrounding the head of the pancreas that precludes a safe pancreaticoduodenectomy
Advantage and Disadvantage
62 % free of pain
95 % satisfactory pain Control
main disadvantage :
» removal of pancreatic parenchyma
» 34% of patients developed endocrine or exocrine pancreatic insufficiency
a single stricture that is proximal to the papilla produces pancreatic duct dilation , Tx ?
> > alternative to a Puestow or Frey procedure
a pancreaticoduodenectomy performed to relieve the obstruction
> > absolutely contraindicated if more than one obstruction is present in the duct.
> > Single distal obstructions can occasionally be treated with a distal pancreatectomy.
> > The main disadvantage of both procedures is that they can be associated with pancreatic insufficiency
predominant mass in the head or, less commonly, in the tail of the pancreas without any evidence of pancreatic duct dilation
> > Resection is recommended for surgical candidates to avoid any error in diagnosis.
> > pancreaticoduodenectomy or duodenum-preserving pancreatic head resection, known as the Beger procedure
> > Roux-en-Y is created and anastomosed to the rim of pancreas or duodenum, pancreatic duct, and body and perhaps the bile duct if it was entered
Diffuse glandular involvement without dilation of the pancreatic duct
The most effective treatment to eliminate pain in patients without dilation of the pancreatic duct is total pancreatectomy.
islet autotransplantation after total pancreatectomy to prevent the effects of surgically induced diabetes.
In pediatric patients with genetic predisposition to pancreatitis, early pancreatectomy and islet autotransplantation is highly effective at improving quality of life
Biliary strictures
> > IV fluid and antibiotic therapy and temporary bile duct decompression with plastic stents is indicated for patients who present with cholangitis.
> > Pancreaticoduodenectomy is indicated for patients in whom malignant disease cannot be excluded before surgery.
> > A Roux-en-Y hepaticojejunostomy is an alternative treatment for patients without evidence of malignant disease or significant scarring that precludes resection of the head of the pancreas.
Duodenal stenosis
Permanent treatment requires a gastrojejunostomy
Pancreatic pseudocyst
> > develop more frequently in patients with chronic pancreatitis compared with AP
> > Spontaneous regression is less likely to occur in these patients because pancreatic pseudocysts arise more frequently in the setting of pancreatic duct obstruction.
> > Indications for treatment include symptoms secondary to gastric, duodenal, or biliary compression or associated complications, such as bleeding, pancreaticopleural fistulas, rupture, or spontaneous bleeding.
How to Drain
> > endoscopic and surgical drainage
drainage with ERCP.
> > drainage with EUS has been shown to be more successful because of improved visualization of vasculature as well as fluid collections and necrosis.
> > Small-caliber plastic stents may be used for simple pancreatic fluid collections or larger metal stents for complex collections or those with infection or necrosis
