Chronic pancreatitis

Chronic pancreatitis (CP) is caused by progressive inflammation and irreversible damage to the structure and function (exocrine and endocrine) of the pancreas. Chronic heavy alcohol use is the most common cause, followed by pancreatic ductal obstruction. Idiopathic pancreatitis accounts for up to 30% of cases. Patients may be asymptomatic or present with abdominal pain and features of pancreatic enzyme insufficiency (e.g., steatorrhea, weight loss, impaired glucose tolerance). Diagnosis is confirmed on imaging, which demonstrates pancreatic calcifications, ductal strictures, and ductal dilations. Pancreatic function tests (e.g., fecal elastase-1 measurement, 72-hour fecal fat estimation) assess the degree of enzyme deficiency. Symptomatic patients are managed with oral pancreatic enzyme replacements and analgesics. Patients with chronic pain require additional interventions (e.g., celiac ganglion block, partial/complete pancreatic resection).

• Chronic heavy alcohol use (60–70% of cases, esp. men) ^[1]
• Pancreatic ductal obstruction (< 10%): strictures (e.g., due to trauma, stones)
• Tobacco use
• Idiopathic pancreatitis (20–30%)
• Hereditary pancreatitis (∼ 1%) ^[2]
  • PRSS1 gene mutation (autosomal dominant inheritance), SPINK1 gene mutation
  • Age of onset < 20 years
  • Characterized by a positive family history and the absence of other risk factors
• Autoimmune pancreatitis
• Systemic disease
  • Cystic fibrosis: ∼ 2% of cystic fibrosis patients develop chronic pancreatitis. ^[3]
  • Severe hypertriglyceridemia (levels > 1,000 mg/dL)
  • Primary hyperparathyroidism (hypercalcemia)
• Tropical pancreatitis
  • Most common cause in the tropics (esp. southern India)
  • Young age at onset

• Autodigestion and inflammation: damage to pancreatic acinar cells; (e.g., alcohol), outflow obstruction of pancreatic enzymes or premature activation of trypsinogen to trypsin → intrapancreatic activation of digestive enzymes (e.g., amylase and lipase) → autodigestion of pancreatic tissue → inflammatory reaction
• Fibrosis: exposure to toxins and/or inflammatory mediators (e.g., alcohol, cytokines) → activation of pancreatic stellate cells

References:^[4]

• Epigastric abdominal pain (main symptom)
  • Pain radiates to the back, is relieved on bending forward, and is exacerbated after eating.
  • Pain is initially episodic and becomes persistent as the disease progresses.
  • Often associated with nausea and vomiting
• Features of pancreatic insufficiency: late manifestation (after 90% of the pancreatic parenchyma is destroyed)
  • Steatorrhea (exocrine enzyme deficiency)
    • Cramping abdominal pain, bloating, diarrhea
    • Can lead to a deficiency of fat-soluble vitamins (A, D, E, and K)
  • Malabsorption and weight loss
  • Pancreatic diabetes (endocrine hormone deficiency)

In the later stages of chronic pancreatitis, patients may not experience any pain.References:^[1][5]

Approach ^[8]

• Initial survey: medical history, risk factors, clinical features suggestive of chronic pancreatitis
• Laboratory testing: helps identify the underlying cause and possible complications (CBC, calcium levels, triglycerides, fasting glucose, liver function tests, pancreatic enzyme levels)
• Confirm diagnosis: via imaging and pancreatic function tests
  • Best imaging modalities: contrast-enhanced CT, MRCP, and endoscopic ultrasound (high specificity, moderate sensitivity)
  • The choice of imaging modality is based on cost, availability, invasiveness, and adverse effects.
• Assess disease severity: Pancreatic function tests (e.g., fecal elastase-1 activity) are used to determine the extent of pancreatic insufficiency.
• Genetic testing: indicated in young patients with idiopathic pancreatitis or a family history of chronic pancreatitis

The STEP-wise approach involves Survey, Tomography/imaging, Endoscopy, and Pancreatic function testing.

Laboratory tests

• Serum pancreatic enzyme levels: Lipase (specific) and amylase (nonspecific) are often normal .

In chronic pancreatitis, pancreatic enzyme levels are often normal and cannot be used to confirm or rule out the diagnosis. In contrast, acute pancreatitis typically causes significant enzyme elevation.

Pancreatic function tests

• Indirect tests
  • Fecal elastase-1 (FE-1) activity: confirms that steatorrhea is due to pancreatic lipase insufficiency ^[9]
    • FE-1 < 200 μg/g: pancreatic exocrine insufficiency
    • FE-1 < 100 μg/g: severe pancreatic exocrine insufficiency
  • 72-hour quantitative fecal fat estimation
    • Patients are asked to consume 100 g of fat per day for 3 days, after which the fecal fat content of their stool is measured.
    • Fecal fat > 7 g per day is diagnostic of steatorrhea.
• Direct tests ^[10]
  • Cholecystokinin test: Cholecystokinin analog (cerulein) is administered intravenously, which stimulates pancreatic enzyme and bicarbonate secretion. This secretion is collected in a tube placed in the duodenum during endoscopy and analyzed.
  • Secretin test: Secretin stimulates pancreatic bicarbonate secretion. The test is performed in the same way as the cholecystokinin test.
  • Cholecystokinin-secretin pancreatic function test: Both of the secretagogues are administered simultaneously and the collected secretion is quantitatively analyzed.

Imaging ^[8][11]

• Abdominal CT (plain and contrast-enhanced CT): best initial imaging modality to screen for CP
  • Findings
    • Pancreatic ductal dilations and calcifications on plain CT (more sensitive than x-ray)
    • “Chain of lakes” appearance of the main pancreatic duct
    • Pancreatic atrophy
  • Can rule out pancreatic carcinoma or gastrointestinal malignancy as a possible cause of epigastric pain and weight loss
• ERCP: detection of early pathologies and simultaneous treatment possible (e.g., duct dilation, stent insertion)
  • Ductal stones, which are visible as filling defects
  • “Chain of lakes” or “string of pearls” appearance (characteristic feature)
  • Irregularity and/or dilation of the main pancreatic duct
• MRCP ^[12]
  • Indicated when CT findings are equivocal but clinical suspicion of CP is high
  • Findings
    • Ductal strictures and dilations
    • Pancreatic calcifications
• Abdominal ultrasound
  • Indistinct margins and enlargement
  • Pancreatic calcifications
  • Ductal strictures, dilation, or stones
• Endoscopic ultrasound (EUS)
  • An invasive test that is reserved for cases in which a CT scan and/or MRCP are nondiagnostic (can detect early changes of CP )
  • Findings
    • Parenchymal lobularity and hyperechoic foci
    • Ductal dilation and calcification ^[13]
• Abdominal x-ray: visible pancreatic calcifications (highly specific, but only seen in ∼ 30% of cases)

Genetic testing ^[14]

Indications: family history of chronic pancreatitis, young patients with idiopathic pancreatitis

• PRSS1 gene mutations: diagnostic of hereditary pancreatitis
• CFTR gene mutations: seen in ∼ 30% of patients with idiopathic chronic pancreatitis
• SPINK1 gene mutations: seen in ∼ 20% of patients with chronic pancreatitis

General measures

• Abstinence from alcohol and nicotine
• Pancreatic enzyme replacement (with meals)
• Small, regular meals (rich in carbohydrates, low in fat)
• Supplementation with medium-chain triglycerides (MCT)
• Parenteral administration of fat-soluble vitamins (A, D, E, K) if necessary
• Endocrine insufficiency: insulin administration
• For more information on the management of acute attacks, see “Acute pancreatitis”.

Pain management

• Analgesics: NSAIDs, opioids for severe pain (e.g., long-acting fentanyl/morphine), low-dose tricyclic antidepressants (e.g., amitriptyline)
• Intractable pain
  • Celiac ganglion block (offers temporary relief)
  • Endoscopic papillotomy with ductal dilation, stent placement, and removal of stones if present
  • Extracorporeal shock wave lithotripsy (ESWL): for intraductal stones

Surgery

• Indication: if pancreatic cancer is suspected or in those with intractable pain
• Procedures
  • Pancreaticojejunostomy: if the main pancreatic duct is dilated (> 5 mm)
  • Resection of the affected part of the pancreas (distal pancreatectomy, Whipple procedure)
  • Thoracoscopic bilateral splanchnicectomy ^[15]

Pancreatic insufficiency

Tissue atrophy and fibrosis cause:

• Exocrine insufficiency → deficiency of lipase, amylase, and protease → maldigestion, steatorrhea, malabsorption
• Destruction of beta cells → endocrine insufficiency with pancreatic diabetes ^[16]

Pancreatic pseudocysts ^[17]

• Definition: encapsulated collection of pancreatic fluid that develops 4 weeks after an acute attack of pancreatitis; (can occur in both acute and chronic pancreatitis )
• Pathophysiology: pancreatic secretions leak from damaged ducts → inflammatory reaction of surrounding tissue → encapsulation of secretions by granulation tissue
• Clinical features ^[18]
  • Often asymptomatic
  • Painless abdominal mass
  • Pressure effects
    • Gastric outlet obstruction (early satiety, nonbilious vomiting, abdominal pain)
    • Obstruction of the distal duodenum (bilious vomiting) → may result in steatorrhea
    • Bile duct obstruction with jaundice
• Diagnostics: abdominal ultrasound/CT/MRI
  • Extrapancreatic fluid collection within well-defined wall/capsule
  • No solid cyst components detectable
• Treatment
  • Cystogastrostomy/cystoduodenostomy/cystojejunostomy
  • Ultrasound/CT-guided percutaneous drainage
• Complications
  • Infection → fever, abdominal pain, sepsis
  • Pseudocyst rupture → pancreatic ascites/pancreaticopleural fistula
  • Erosion into an abdominal vessel → hemorrhage into the cyst → sudden abdominal pain, signs of hemorrhagic shock

Splenic vein thrombosis ^[19]

• Epidemiology: Occurs in 10% of patients with chronic pancreatitis
• Pathophysiology: inflammation of the splenic vein → thrombus formation → left-sided portal hypertension → gastric varices
• Clinical features: can present with upper GI bleeding, ascites, and splenomegaly
• Diagnostics: ultrasound with doppler, CT/MR angiography
• Treatment
  • Acute: anticoagulation and/or thrombectomy
  • Chronic and symptomatic: splenectomy

Pancreatic ascites

• Pathophysiology: ductal disruption (due to an acute attack of pancreatitis, pancreatic surgery and/or trauma) or a pseudocyst leak/rupture → pancreatic ascites
• Clinical features
  • Abdominal distention; variable abdominal pain
  • Dyspnea
  • Peripheral edema
  • Free fluid in the peritoneal cavity
• Diagnostics
  • Ascitic fluid analysis: exudate with high amylase levels (> 1,000 IU/L)
  • Imaging: ERCP, CECT, MRCP
    • Identify ascites and the site(s) of the leak
    • ERCP is preferred, as it allows treatment to be performed in the same sitting.
• Treatment ^[20]
  • Conservative management: indicated in all patients; ∼ 30% require no further treatment
    • Nothing by mouth, IV fluids, parenteral nutrition
    • Somatostatin analogs (octreotide)
    • Repeated ascitic taps
  • Stenting of the pancreatic duct: if ERCP shows ductal disruption ^[21]
  • Surgery: indicated in patients showing no improvement after 4 weeks of conservative management (see “Pancreatic and hepatic surgery”)
    • Pancreatic resection
    • Surgery for pancreatic pseudocyst
    • Lateral pancreaticojejunostomy

Further complications

• Pancreatic abscess
• Portal vein thrombosis
• Pancreatic diabetes
• Pancreatic cancer (especially in patients with hereditary pancreatitis)

We list the most important complications. The selection is not exhaustive.