• Clinical science

Chronic pancreatitis

Abstract

Chronic pancreatitis is caused by progressive inflammation and irreversible damage to the structure and function (exocrine and endocrine) of the pancreas. Alcohol abuse is the most common known etiological factor, 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 successfully managed with oral pancreatic enzyme replacements and analgesics. Patients with chronic pain require additional interventions (e.g., celiac ganglion block, partial/complete pancreatic resection).

Etiology

References:[1][2][3][4]

Classification

  • Classifying chronic pancreatitis is clinically irrelevant but allows a certain degree of comparison between clinical findings.
  • Recommended for classifying the initial diagnosis and follow-ups
Cambridge classification of chronic pancreatitis
Imaging type
ER(C)P Ultrasound Endosonography CT/MRCP
Score 0
  • Visualization of the entire duct system, no abnormal signs
  • Normal parenchyma, regular organ contour, duct < 2 mm
  • Normal
  • Normal
Score 1
  • Increased parenchymal echogenicity, lobular and honeycomb-like parenchymal structure, enlargement (up to 1.5 times), main duct < 3 mm
  • Lobular and honeycomb-like parenchymal structure, main duct < 3 mm
  • Abnormalities not detectable on CT or MRCP
Score 2
  • Lobular parenchymal texture with hyperechogenic septa, irregular pancreatic contour, irregular main pancreatic duct (hyperechogenic) > 3 mm
  • Echogenic parenchymal contour, hyperechogenic focal lesions, hyperechogenic main duct < 3 mm
  • At least 2 of the following:
    • Main duct 2–4 mm in the pancreatic body
    • Minor enlargement
    • Parenchymal heterogeneity
    • Small (< 10 mm) cystic changes
    • Irregular main duct
    • > 3 abnormal side branches
Score 3
  • Score 2 + cysts and focal calcification
  • Honeycomb-like parenchymal structure with septa, hyperechogenic focal lesions, irregular main duct > 3 mm, no ductal stones
  • Score 2 (all criteria) + main duct > 4 mm
Score 4
  • Score 3 + cysts, ductal stones, strictures and/or invasion of surrounding organs
  • Score 3 + ductal stones, ductal obstruction, enlargement (at least twice the usual organ size) and/or splenic vein thrombosis
  • Score 3 + calcification, ductal stones and/or cysts
  • At least 1 from above (score 2 and 3) plus
    • Cystic structures > 10 mm
    • Parenchymal calcification
    • Intraductal filling defects (concrement)
    • Ductal obstruction (strictures)
    • Severe ductal irregularities

Pathophysiology

References:[1][5]

Clinical features

  • Epigastric abdominal pain (main symptom)
    • Pain radiates to the back, is relieved on bending forwards and 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 hormone deficiency)
      • Cramping abdominal pain, bloating, diarrhea, weight loss
      • May cause fat-soluble vitamin deficiencies (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][2][6]

Subtypes and variants

Autoimmune pancreatitis

  • Definition: chronic pancreatitis associated with other conditions and with clinical features similar to pancreatic cancer
  • Type I (IgG4-related pancreatitis, ∼ 60%)
    • Sex: >
    • Clinical features
      • See “Clinical features” above; weakness, extreme fatigue, weight loss
      • Multiorgan involvement (IgG4-associated autoimmune diseases)
    • Serology: characterized by ↑ IgG4
    • Histology: fibrosis, lymphoplasmacytic sclerosing pancreatitis, absence of neutrophils
  • Type II ∼ 40%
    • Sex: =
    • Clinical features: see “Clinical features” above; associated with inflammatory bowel disease
    • Serology: often normal
    • Histology: fibrosis and neutrophil infiltrates (granulocytic epithelial lesion)
  • Diagnostics
  • Management
  • Relapse rate: ∼ 50% in case of type I

Diagnostics

The diagnosis of chronic pancreatitis is based primarily on characteristic findings on CT or MRCP imaging, since pancreatic enzyme levels are usually normal and cannot confirm or rule out the diagnosis. Additional pancreatic function tests are used to assess the extent of pancreatic insufficiency.

Imaging

  • Abdominal CT (plain and contrast-enhanced): best initial imaging modality to screen for CP
    • Findings: pancreatic atrophy, pancreatic ductal dilations; pancreatic ductal calcifications on plain CT (more sensitive than x-ray); chain of lakes” appearance
    • Can simultaneously rule out a pancreatic carcinoma or a gastrointestinal malignancy as a possible cause of epigastric pain and weight loss
  • MRCP: indicated when CT findings are equivocal but clinical suspicion of CP is high
    • Findings: ductal strictures and dilations, pancreatic calcifications
  • Abdominal x-ray: visible pancreatic calcifications (highly specific, but only seen in ∼ 30% of cases)
  • Ultrasound
    • Abdominal ultrasound: indistinct margins and enlargement; pancreatic calcifications; ductal strictures, dilation or stones
    • Endoscopic ultrasound: parenchymal lobularity and hyperechoic foci; ductal dilation and calcification
  • ERCP: detection of early pathologies and simultaneous treatment possible (e.g., duct dilation, stent insertion)
    • Ductal stones, seen as filling defects
    • Chain of lakes” or “string of pearls” appearance (characteristic feature)
    • Irregularity, dilation of the main pancreatic duct

Laboratory tests

Genetic testing

  • Indication: family history of chronic pancreatitis; young patients with idiopathic pancreatitis
  • PRSS-1 mutations: diagnostic of hereditary pancreatitis
  • CFTR gene: 40% of patients with idiopathic chronic pancreatitis have a CFTR gene mutation.
  • SPINK-1 gene mutations seen in 25% of patients with chronic pancreatitis (esp. tropical pancreatitis).

References:[1][7][8][9][10][11]

Treatment

General measures

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

Pain management

Surgery

References:[1][12][13]

Complications

Pancreatic pseudocysts

  • Definition: : encapsulated collection of pancreatic fluid; which 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
    • Often asymptomatic
    • Painless abdominal mass
    • Pressure effects
      • Gastric outlet obstruction (early satiety, non-bilious vomiting, abdominal pain)
      • Obstruction of the distal duodenum (bilious vomiting)
        • Results in steatorrhea
      • Bile duct obstruction with jaundice
  • Diagnostics: abdominal ultrasound/CT/MRIextrapancreatic fluid collection within well-defined wall/capsule, no solid cyst components detectable
  • Treatment: : Surgical/endoscopic cystogastrostomy/cystoduodenostomy/cystojejunostomy ; ultrasound/CT-guided percutaneous drainage
  • Complications

Splenic vein thrombosis

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

Pancreatic ascites

Further complications

References:[14][15][16][17][6][1]

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