Pancreatic Cancer

Clinical Background

Pancreatic cancer, a common cancer in the U.S., has historically been associated with a high mortality rate.

Epidemiology

• Incidence – 9-10/100,000
• Age – peak incidence in 60s
• Sex – M>F (minimal)
• Ethnicity – 30-40% higher incidence in African Americans

Risk Factors

• Low socioeconomic status
• Male gender
• Tobacco use
• Presence of chronic disease states
  • Chronic pancreatitis
  • Diabetes mellitus
  • Prior cholecystectomy
• Occupational exposures
  • DDT, benzidine, dry cleaning agents, polychlorinated biphenyls (PCBs)
• Genetics
  • Family history of pancreatic cancer
  • Familial syndromes
    • BRCA1 and BRCA2 mutations
    • Familial atypical multiple mole melanoma syndrome (FAMMM)
    • Peutz-Jeghers syndrome (PJS)
    • Hereditary nonpolyposis colorectal cancer (HNPCC)
    • Ataxia-telangiectasia syndrome (A-T)
    • Hereditary pancreatitis syndrome
    • Von Hipple-Lindau syndrome (VHL)
    • Li-Fraumeni syndrome (LFS)
    • Familial pancreatic cancer

Pathophysiology

• Tumor is usually ductal adenocarcinoma
  • May also have mucinous cystadenocarcinomic variants
• Uncommon neuroendocrine tumors may also affect the pancreas
  • Insulinoma
  • Glucagonoma
• 70-80% of tumors are located in head of the pancreas
• Tumors may manifest solely as cysts

Clinical Presentation

• No specific early warning symptoms
• Usually abdominal pain and weight loss
• Obstructive jaundice if tumor is at the head of the pancreas
• Late features – ascites, abdominal mass
• If tumors are neuroendocrine in nature, patient may have endocrine syndromes as initial presentation (eg, hypoglycemia)

Diagnosis

Indications for Testing

• Patient presents with jaundice and pancreatic mass
• Monitoring for tumor recurrence after surgery

Laboratory Testing

• CA 19-9 serum antigen testing – sensitivity depends on stage of cancer (70-90% sensitivity and 90% specificity)
  • May be elevated in benign obstructive jaundice, chronic pancreatitis
  • Should be used in conjunction with imaging studies to diagnose pancreatic cancer
  • Limited use as early screening
• Serial monitoring recommended to assess follow up after potentially curative surgery or response to palliative chemotherapy
• Other potential markers include MUC-1 antigen (also known as CA15-3 antigen) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) – although neither has been sufficiently validated for pancreatic cancer
• Cystic lesions – fluid concentrations of amylase, carcinoembryonic antigen (CEA), and CA 19-9
  • Levels suggesting a diagnosis of cancer
    • Amylase <250 U/mL
    • CEA >800 ng/mL
    • CA 19-9 >37 U/mL
• KRAS2 gene mutation in ductal adenocarcinoma is common
• FISH detection of aneuploidy for chromosomes 3, 7 and 17 and loss of the 9p21 locus is helpful in establishing the diagnosis of pancreatic ductal carcinoma in cytologic specimens

Histology

• Biopsy of tumor with histologic evaluation
  • Fine needle aspiration (FNA) via EUS is initial procedure of choice for diagnosis

Imaging Studies

• Transabdominal ultrasound/CT/MRI
• Endoscopic retrograde cholangiopancreatography (ERCP) to outline extent of ductal involvement

Screening

Monitoring

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Carcinoembryonic Antigen, Fluid 0020742 Method: Electrochemiluminescent Immunoassay	Assist with evaluating pancreatic cysts as benign or malignant