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Definition

• Cancer originating in the pancreas
  • Histologic types
    • Ductal adenocarcinomas: > 90%
    • Islet-cell tumors: remaining 5–10%
  • Location
    • Pancreatic head (70%)
    • Body of pancreas (20%)
    • Tail of pancreas (10%)

Epidemiology

• Incidence/prevalence in the U.S. in 2007
  • New cases: 37,170
    • Incidence is decreasing somewhat.
  • Deaths: 33,370
    • Fourth most common cause of cancer-related mortality
    • Results in death of > 98% of afflicted patients
• Sex
  • More frequent in men than women (1.3:1)
    
• Race
  • More frequent in African American persons than white persons (1.5:1)
    
• Age
  • Rarely develops before 50 years of age
    

Risk Factors

• Cigarette smoking
  • Most consistent risk factor
  • 2–3 times more common in heavy smokers than nonsmokers
• Chronic pancreatitis
• Longstanding diabetes mellitus
• Obesity
  • Risk directly related to increased caloric intake
• Hereditary factors
  • 5–10% of patients have a first-degree relative with pancreatic cancer.
  • Risk is elevated in the following genetic syndromes.
    • Hereditary chronic pancreatitis (40% lifetime risk)
    • Peutz–Jeghers syndrome (up to 36% lifetime risk)
    • Von Hippel–Lindau syndrome
    • BRCA-2 germline mutations (10-fold increased risk)
      
• History of partial gastrectomy (2- to 5-fold risk)
  
• Not thought to be risk factors
  
  • Alcohol abuse
  • Cholelithiasis
  • Coffee consumption

Etiology

• Etiology is unknown.
• Pathogenesis
  • Associated gene mutations
    • Mutations in K-ras genes: >85% of specimens of human pancreatic cancer
    • Mutation of the p16 ^INK4 gene located on chromosome 9p21
      • Gene also implicated in the pathogenesis of malignant melanoma
    • Mutations of the p53, DPC4, and BRCA2 tumor suppressor genes
  • A series of molecular events involving a sequence of these mutations has been proposed to occur as the normal pancreatic duct progresses through dysplasia to infiltrating carcinoma.
    

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