Description

• Carcinoma of the exocrine pancreas is the 4th most common cause of cancer death in the US.
• Rarely curable: Overall 1-year and 5-year relative survival rates of 25% and 5%, respectively.
• 60–70% occur in the head, 15% in the body, 5% in the tail; 20% diffusely involve the gland.
• <20% are localized at diagnosis. For localized, small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule, surgical resection has 5-year survival of 18–24%.
• In apparently resectable disease, 20–40% have unresectable lesions at surgery.
• Ampullary, duodenal, or distal bile duct tumors may mimic pancreatic carcinoma and are more likely to be resectable and curable.
• For advanced or unresectable cancers, survival is <1% at 5 years; most patients die within 1 year.

Epidemiology

During 2003–2007, median age at diagnosis = 72 years; rare younger than age 45; after 45, occurrence rises sharply.

• An estimated 42,470 people diagnosed in 2009 (21,040 men and 21,420 women); 35,240 deaths
• More common in black and white races, 16.7 and 10.3 in 100,000 men and 14.4 and 10.3 in 100,000 women, respectively. Among Hispanic and Asian/Pacific Islanders there is an incidence of 10.9 and 8.3 in 100,000 men and 10.1 and 8.3 in 100,000 women, respectively (1).

Prevalence
In 2008, in the US, ~34,600 men and women (16,811 men and 17,846 women) were alive who had a history of pancreatic cancer.

Risk Factors

• Smoking: Relative risk (RR) = 1.5; correlates with amount smoked
• Diabetes: RR = 2.1 (95% CI, 1.6–2.8); as many as 1 in 6 become diabetic within 6 months before diagnosis.
• Prior partial gastrectomy or cholecystectomy: 2–5-fold increased risk 15–20 years after gastrectomy
• Familial aggregation/genetic factors: 5–10% of patients have a 1st-degree relative with the disease, which confers a 9-fold increase in risk vs. the general population (2).
• Hereditary chronic pancreatitis: Cumulative risk by ages 50 and 75 is 10% and 54%, respectively.
• Chronic pancreatitis: Tropical and nontropical
• Non-O blood type
• High intake of dietary fat and obesity
• Alcohol: Recent data indicate a modest increase in risk confined to heavy alcohol consumers (3).
• Coffee intake, aspirin and NSAID use NOT regarded as a risk factors.

• Multifactorial: Mutational activation of oncogenes (e.g., K-ras mutation 90%); inactivation of tumor-suppressor genes (e.g., p16/CDKN2A [95%], TP53 [75–85%], SMAD4 [30%], and BRCA2 genes [10%]); and defects in DNA mismatch repair genes (e.g., hMLH1 and hMSH2 [4% of tumors])
• Hereditary pancreatitis: Cumulative risk of pancreatic cancer in affected family members by age 70 is estimated to be 40%.
• Inherited cancer syndromes:
  • Peutz-Jeghers syndrome: Related genes: PRSS1 and STK 11; lifetime risk is as high as 36%.
  • Hereditary breast/ovarian cancer: 5% lifetime risk for pancreas cancer; related genes: BRCA2 and BRCA1
  • Familial atypical multiple-mole melanoma syndrome: 19% lifetime risk; related gene: CDKN2A
  • Ataxia-telangiectasia: Related gene: ATM
  • Li-Fraumeni syndrome: Related gene: p53

General Prevention

Routine screening is not recommended. Even with a strong family history or predisposition syndromes, utility and cost-effectiveness of screening are unclear.

Pathophysiology

• Pancreatic intraepithelial neoplasia: Best characterized precursor lesion. Progression to severe dysplasia is marked by expression of multiple oncogenes.
• K-ras mutations and telomere shortening are the earliest known genetic abnormalities, even in low-grade intraepithelial neoplasia.

Commonly Associated Conditions

• See “Genetics.”
• Chronic pancreatitis; diabetes mellitus; inherited cancer syndromes, as noted above