Malignant Pancreas Disease

I

1.
Fourth most common cause of adult cancer mortality in the United States (8th leading cause worldwide)
2.
Approximately 50,000 new cases/year nationally with high expected mortality
3.
Slight male sex predominance; 1.3:1 male/female ratio
4.
Dramatically increases after age 45; peaks in seventh and eighth decades of life
5.
Higher incidence in Western and industrialized world
6.
Incidence rates are highest in native inhabitants of New Zealand and Hawaii and in Black Americans
7.
Overall lifetime risk for developing pancreatic cancer is 0.5% by age of 70

1.
Cigarette smoking (2–3× increased risk)—increases with duration and amount; risk is reduced with smoking cessation. May account for up to 25% of all cases
2.
Genetic Predisposition and Familial Pancreatic Cancer—account for ∼10% of pancreatic cancers
- a.
  BRCA1 — 3 × increased risk
- b.
  BRCA2 — 3 – 10 × increased risk
  - (1)
    PALB2 mutations—PALB2 localizes with BRCA2 and has similar effect of BRCA2 mutations.
- c.
  Lynch syndrome — mismatch repair gene mutations
- d.
  PRSS1 mutations — chronic pancreatitis, 50% of patients will develop pancreatic cancer by age 70
- e.
  Peutz-Jeghers
- f.
  Ataxia-telangiectasia
- g.
  Li-Fraumeni syndrome p53 mutation
- h.
  Familial pancreatic cancer: defined as patients with two or more first-degree relatives with pancreatic cancer, unknown genetic predisposition, 4 – 10-fold increased risk for development of pancreatic cancer, which increases directly proportional to the number of affected family members
3.
Chronic pancreatitis—extent of risk is controversial but may be up to 15-fold increase.
4.
Others factors are less clear.
- a.
  Diabetes mellitus
- b.
  Caffeine
- c.
  Alcohol
- d.
  Obesity
- e.
  ABO blood group: A, AB, and B blood types may have increased risk.
- f.
  Helicobacter pylori infection

1.
Ninety-five percent of pancreatic neoplasms originate from exocrine cells (remainder are of endocrine origin).
2.
Pancreatic adenocarcinoma subtypes/variants include ductal adenocarcinoma (90% of cases), giant cell carcinoma—(4%), adenosquamous carcinoma—(3%), mucinous carcinoma—(2%), mucinous cystadenocarcinoma—(1%), acinar cell carcinoma—(1%)
3.
Most common rumor location: head (60%), body (10%), tail (5%)
4.
Ninety-five percent of pancreatic adenocarcinomas have KRAS mutations
5.
Precursor lesions
- a.
  Pancreatic intraepithelial neoplasia (PANIn) is a pancreatic ductal lesion that does not penetrate the basement membrane but demonstrates neoplastic growth and genetic mutations. Considered a precursor lesion to adenocarcinoma
- b.
  Graded from 1 to 3 based on number of mitoses, necrosis, nuclear atypia, and papillary component
- c.
  PANIn grade 3 lesions are found in over half of individuals with invasive pancreatic cancer.
- d.
  Presence of PANIn lesions at resection margin does not affect survival/recurrence.
- e.
  Multi-hit phenomenon from PANIn to carcinoma follows a particular sequence of genetic alterations: KRAS → CDKN2A → p53 and SMAD4.

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