Chronic pancreatitis Pancreatic cancer Flashcards
What mechanisms control pancreatic secretion?
Hormonal (secretin and cholecystokinin) and neuronal mechanisms.
Where is secretin released from, and what does it stimulate?
Released from the duodenal mucosa.
Primarily stimulates the release of bicarbonate and water from the interlobular duct cells of the pancreas.
Where is cholecystokinin (CCK) released from, and what does it stimulate?
Released from gut endocrine cells in response to the entry of fat and protein into the proximal intestine.
Stimulates pancreatic acinar cells to release digestive proenzymes.
causes of exocrine pancreatic insufficiency ?
Chronic pancreatitis (the most common cause);
Cystic fibrosis
Pancreatic resection
Pancreatic duct obstruction
Shwachman-Diamond syndrome - bone marrow failure and exocrine
pancreatic disorder
Other
What are the key pathological changes in chronic pancreatitis?
Inflammation, fibrosis, and loss of pancreatic tissue (acinar cells and cells from Langerhans isle).
What functional deficits result from chronic pancreatitis?
Loss of pancreatic exocrine function (digestion) and endocrine function (insulin and glucagon).
etiology (TIGAR-O)
T = toxic - metabolic
I = idiopathic
G = genetic
A = autoimmune
R = recurrent
O = obstructive
The majority of cases have more than one etiologic factor as a cause of
chronic pancreatitis.
What are the primary toxic and metabolic factors contributing to chronic pancreatitis?
Alcohol, smoking, and hypertriglyceridemia.
What is the typical alcohol consumption pattern associated with increased risk of chronic pancreatitis?
Minimum 5 drinks/day for at least 5 years (though there’s no precise value).
What percentage of heavy alcohol consumers develop chronic pancreatitis, and what is a significant co-factor?
< 5%
Smoking is a significant co-factor.
What is the relationship between smoking and chronic pancreatitis?
Synergistic effect with alcohol, dose-dependent.
Increases the risk of pancreatic cancer.
How does hypertriglyceridemia contribute to chronic pancreatitis?
Patients with acute pancreatitis secondary to high triglyceride levels frequently progress to chronic pancreatitis.
What is a key genetic mutation associated with chronic pancreatitis, and how does it contribute to the disease?
Cationic trypsinogen gene mutation (PRSS1).
Determines the formation of abnormal trypsin, which leads to activation of other enzymes and continuous pancreas damage.
What are other genetic factors implicated in chronic pancreatitis?
SPINK1, CFTR
What are the characteristics of Type I autoimmune chronic pancreatitis?
High levels of serum IgG4.
Histopathology (HP) shows lymphoplasmacytic sclerosing pancreatitis.
Associated with extra-pancreatic manifestations like biliary strictures, hilar lymphadenopathies, retroperitoneal fibrosis, interstitial nephritis
What are the characteristics of Type II autoimmune chronic pancreatitis?
Affects only the pancreas.
Normal serum levels of IgG4.
What is the strongest risk factor for the progression to chronic pancreatitis related to previous acute pancreatitis?
Recurrent episodes of acute pancreatitis
What are obstructive factors that can lead to chronic pancreatitis?
Chronic obstruction of the main pancreatic duct: tumors, stones, stenosis, duodenal wall cyst.
What are the characteristics of early-onset idiopathic chronic pancreatitis?
Mean age 20 years.
Predominant pain.
Difficult diagnosis due to lack of clear clinical and laboratory characteristics
What is the general pathway of pathogenesis in chronic pancreatitis?
Etiologic factor → injury → healing through fibrosis → loss of acinar, islet, and ductal cells → loss of pancreatic function.
How does alcohol contribute to pancreatic injury in chronic pancreatitis?
Through toxic metabolites, apoptosis gene activation, and direct activation of stellate acinar cells.
What is the most common clinical symptom of chronic pancreatitis?
abdominal pain
Describe the characteristics of abdominal pain in chronic pancreatitis.
Epigastric pain, often radiates to the back.
Sometimes postprandial exacerbations.
Can be associated with nausea, vomiting, anorexia.
Can be constant or episodic.
A change in pattern or sudden worsening indicates possible complications.
What is steatorrhea, and what does it indicate in chronic pancreatitis?
Oily or floating stool (fat maldigestion).
Indicates a loss of at least 90% of pancreatic exocrine secretory function.
What is the significance of weight loss in chronic pancreatitis?
Sarcopenia (muscle wasting) is associated with an increased risk of death.
Can chronic pancreatitis be asymptomatic?
Yes, in a small number of patients.
Diagnosis may be made incidentally through imaging for other reasons.
When might clinical manifestations be absent in chronic pancreatitis?
In the early stages of the disease.
What is the utility of lipase and amylase in chronic pancreatitis outside of acute episodes?
hold no value
What happens to lipase and amylase levels during acute episodes in chronic pancreatitis?
Amylase and lipase > 3 x ULN.
Peak levels tend to decrease with each pain flare.
In late stages, elevation can be minimal due to progressive loss of acinar cells.
What do elevated serum bilirubin and alkaline phosphatase suggest in chronic pancreatitis?
Compression of the bile duct (by edema, fibrosis, or pancreatic cancer).
What vitamin deficiencies are common in chronic pancreatitis, and what are the associated risks?
Deficiencies of fat-soluble vitamins, particularly vitamin D.
Risk of metabolic bone disease.
What is involved in direct pancreatic function testing?
Administration of stimulatory hormones (CCK or secretin).
CCK stimulates acinar cell secretion of digestive enzymes.
Secretin stimulates ductal cell secretion of bicarbonate-rich fluid.
Secreted fluid is collected by an oroduodenal tube or upper endoscope.
It can identify early stages of chronic pancreatitis more accurately.
What is involved in indirect pancreatic function testing?
Measurement of pancreatic enzymes in stool (chymotrypsin and elastase tests).
Levels < 100 mcg/g stool indicate exocrine pancreatic insufficiency.
What are the findings on a plain abdominal radiograph that suggest chronic pancreatitis?
Diffuse pancreatic calcifications seen incidentally.
Takes years to develop.
Vascular calcifications may be misleading.
What are the findings on abdominal ultrasound that suggest chronic pancreatitis?
Increase in echogenicity, atrophy, dilated pancreatic duct, pancreatic duct stones.
Limited diagnostic utility.
Similar echotexture modifications can be seen in old individuals, long-standing diabetes type I or II.
What are the findings on a CT scan that suggest chronic pancreatitis?
Atrophy of the pancreas, ductal dilatation, parenchymal and intraductal calcifications.
In early stages, the aspect can be normal.
What cross-sectional imaging modalities are used to diagnose chronic pancreatitis, and what are their advantages?
CT scan or MRI with MRCP.
High sensitivity and specificity.
What are the findings on MRI that suggest chronic pancreatitis?
Drop in signal in T1 sequences.
Glandular atrophy, irregular pancreatic duct contour, focal areas of narrowing or dilatation.
Ductal findings in early stages can be normal.
What is the primary advantage of using endoscopic ultrasound (EUS) in the evaluation of chronic pancreatitis?
Highly detailed examination of the pancreas and ducts
What other conditions or factors can show similar EUS changes as chronic pancreatitis?
Chronic alcohol drinkers, smokers, diabetes, older individuals, chronic renal disease.
What is an additional advantage of performing an EUS in the evaluation of chronic pancreatitis?
Biopsies can be taken during EUS for suspicious lesions.
When should chronic pancreatitis be suspected?
In patients with typical clinical manifestations or relapsing acute pancreatitis.
What is the initial imaging modality used for diagnosing chronic pancreatitis?
Cross-sectional imaging (CT or MRI).
What diagnostic methods are used when cross-sectional imaging is inconclusive in suspected chronic pancreatitis?
Direct pancreatic function test or EUS (endoscopic ultrasound)
Differential diagnosis
Pancreatic ductal adenocarcinoma;
Intraductal papillary mucinous neoplasm;
Cystic neoplasm;
What lifestyle changes are crucial in the management of chronic pancreatitis?
Stop alcohol consumption and smoking.
What dietary recommendations are important for patients with chronic pancreatitis?
Low to moderate fat meals.
High protein foods.
Small meals.
What vitamin supplementation is often necessary for patients with chronic pancreatitis?
Vitamin D and calcium.
What are the general principles of pain management in chronic pancreatitis?
Exclude other causes of pain.
Minimize opioids if possible.
Use non-narcotics as first-line (NSAIDs or acetaminophen).
Narcotics (tramadol) may be used.
Adjunctive agents: tricyclic antidepressants, serotonin reuptake inhibitors, gabapentinoids.
How can pancreatic enzyme supplementation help in chronic pancreatitis?
May reduce pain.
What pain management options are available for patients with non-dilated pancreatic ducts?
Celiac plexus block (injection of an anesthetic in the celiac plexus, can be repeated “as-needed”).
Surgical resection: pancreatoduodenectomy (Whipple operation); duodenum preserving pancreatic head resection; total pancreatectomy with islet cell autotransplantation.
What intervention is required for patients with dilated pancreatic ducts in chronic pancreatitis?
Require drainage of the pancreatic duct if it is obstructed.
Endoscopic or surgical procedures.
What is a pseudocyst, and what complications can it cause in chronic pancreatitis?
Mature fluid collection with a well-defined wall.
Most are asymptomatic.
Can cause intestinal or biliary obstruction due to mass effect.
What types of obstruction can occur as complications of chronic pancreatitis?
Bile duct obstruction.
Duodenal obstruction.
What are the characteristics of pancreatic ascites/pleural effusion in chronic pancreatitis?
Amylase concentration in fluid is usually > 1000 UI/L.
SAAG (serum-ascites albumin gradient) < 1.1.
Proteins > 3 g/dL.
What vascular complications can occur in chronic pancreatitis?
Pseudoaneurysms (splenic artery, g-d artery, p-d artery).
Splenic vein thrombosis and gastric varices.
What are the symptoms of biliary obstruction in chronic pancreatitis?
Nausea.
Vomiting.
Jaundice.
What are the symptoms of duodenal obstruction in chronic pancreatitis?
Early satiety.
Post-prandial pain.
Nausea.
Vomiting
Where do the majority of pancreatic cancers develop?
70% in the head of the pancreas.
10% in the body.
15% in the tail of the pancreas.
What other long-term complications can develop in chronic pancreatitis?
Pancreatogenic diabetes (type 3c diabetes).
Osteopenia, osteoporosis.
Pancreatic cancer.
Addiction to narcotics.
What percentage of pancreatic cancers are derived from exocrine tissue, and what percentage are neuroendocrine tumors (NET)?
95% from exocrine tissue.
5% are neuroendocrine tumors (NET).
What is the mortality associated with pancreatic cancer?
High mortality.
4th cause of mortality due to neoplasia (in USA).
6th cause in the world.
What is the most common type of pancreatic cancer?
Ductal adenocarcinoma.
What genetic factors are associated with pancreatic cancer?
Familial pancreatic cancer.
Genetic mutations.
What are the risk factors for pancreatic cancer?
Smoking, obesity, and sedentarism.
Diet (inconclusive results).
Excess alcohol consumption.
Diabetes.
Chronic pancreatitis.
What are the three most common clinical manifestations of pancreatic cancer?
Pain
Jaundice
Weight loss
What are other common symptoms of pancreatic cancer?
Loss of appetite
Asthenia (weakness)
Back pain
Nausea
Vomiting
Diarrhea
Steatorrhea (oily stools)
Dark urine
Acute pancreatitis
What are some physical signs that may be observed in patients with pancreatic cancer?
Jaundice
Hepatomegaly (enlarged liver)
Cachexia (severe weight loss and muscle wasting)
Right upper quadrant or epigastric mass
Courvoisier’s sign (palpable, non-tender gallbladder)
Ascites (fluid buildup in the abdomen)
How do the clinical manifestations of pancreatic cancer vary?
The manifestations depend on the localization of the tumor.
What is pancreatic panniculitis, and what is its significance?
Erythematous subcutaneous areas of nodular fat necrosis, typically on the legs.
It may be due to systemic spillage of pancreatic enzymes.
Described as well in NET, chronic pancreatitis.
Which liver function tests can be altered in pancreatic cancer?
Aminotransferases
Total bilirubin
Direct bilirubin
Alkaline phosphatase
What are some signs of metastatic disease in pancreatic cancer?
Liver metastases
Ascites
Virchow node (left supraclavicular lymphadenopathy)
Sister Mary Joseph nodule (umbilical nodule)
When is lipase used in the context of pancreatic disease?
Lipase is used for acute pancreatitis.
What is the role of CA 19-9 in pancreatic cancer?
CA 19-9 is a tumoral marker.
It doesn’t establish or exclude the diagnosis.
It can be elevated in other types of cancer, benign biliary, or pancreatic disorders.
It’s not recommended as a screening tool for pancreatic cancer.
What are the roles of MRI and MRCP in pancreatic cancer?
MRCP is better than CT for defining the anatomy of the biliary tree and pancreatic duct.
MRCP is at least as sensitive as ERCP in detecting pancreatic cancers.
What information does a CT scan provide in the evaluation of pancreatic cancer?
More information about the tumor.
Size.
Contact with vessels.
Metastatic disease.
What are the advantages and risks of ERCP in pancreatic cancer?
Advantages:
Invasive.
Has the advantage of collecting tissue samples and stent placing if needed.
Superior to abdominal US and CT for extrahepatic biliary obstruction.
Risks:
Pancreatitis.
Cholangitis.
Bleeding.
What are the advantages of EUS (endoscopic ultrasound) in pancreatic cancer?
Superior to CT for small tumors.
Biopsies can be taken.
How is the definitive diagnosis of pancreatic cancer made?
Made on histopathological examination (not on signs and symptoms).
What are some differential diagnoses for jaundice?
Choledocholithiasis (gallstones in the common bile duct)
Biliary obstruction from other
malignant tumors or adenomas
Intrahepatic cholestasis
Acute or chronic hepatocellular injury
What are some differential diagnoses for weight loss?
Other neoplasia
Thyroid dysfunction
Psychiatric conditions
What are differential diagnoses for solid pancreatic tumors?
Pancreatic cancer
Neuroendocrine tumor
Lymphoma
Metastasis (very rare)
Autoimmune pancreatitis
What are differential diagnoses for cystic pancreatic tumors?
Neo-neoplastic cysts
Pancreatic pseudocyst
Pancreatic cystic neoplasm
Serous cystic tumors
Mucinous cystic neoplasms
How are cystic neoplasms diagnosed?
Fine needle aspiration cytology
What are alarm signs associated with pancreatic cysts?
Jaundice
Diameter > 3 cm
Dilatation of the main duct
Manifestations of acute pancreatitis
What does metastatic disease indicate in terms of resectability?
Metastatic disease = unresectable.
What does local vascular invasion indicate in terms of resectability?
Local vascular invasion = criteria of unresectable disease.
When is exploratory laparotomy used in pancreatic cancer?
Sometimes used for staging.
What is the only curative treatment for pancreatic cancer?
Surgical resection.
What surgical procedure is used for cancer located in the head of the pancreas?
Whipple procedure (pancreatoduodenectomy).
What surgical procedure is used for cancer located in the body or tail of the pancreas?
Distal pancreatectomy.
