Chapter 28. Tumors of the Pancreas

Essentials of Diagnosis

• Elevated CA 19-9 in ~80% of patients.
• Helical pancreatic protocol computed tomography (PPCT) is generally the best initial modality for diagnosis and staging.
• Endoscopic ultrasound (EUS) is superior to CT in diagnosing small tumors, and portal and splenic vein invasion.
• Less than 15% of tumors are resectable at the time of diagnosis.

General Considerations

Pancreatic cancer is the second-most-common gastrointestinal malignancy, and the fourth leading cause of cancer-related deaths in the United States. Less than 4% of patients are alive 5 years after diagnosis. Approximately 34,000 new cases were diagnosed in 2006, and 37,000 new cases were expected to be diagnosed in 2008.

The disease is more common in men than in women (1.3:1) and in certain ethnic and racial groups (eg, Blacks, Polynesians, and native New Zealanders). It is rare before the age of 45 years, but the incidence increases sharply after the seventh decade.

Pathogenesis & Risk Factors

Most pancreatic neoplasms arise from the three different types of the epithelial cells found in the pancreas. Acinar cells account for 80% of the volume of the gland but constitute 1% of exocrine tumors. Ductal cells constitute 10–15% of the volume but give rise to 90% of all tumors. Endocrine cells are 1–2% of volume and account for 1–2% of the tumors. Nonepithelial tumors are very rare.

Approximately 70% of ductal tumors are localized to the head of the pancreas, 5–10% to the body, and 10–15% to the tail. These tumors are hard in consistency due to the strong desmoplastic response they elicit.

Acinar tumors present as large pancreatic masses in the elderly, and distant metastasis is usually present at the time of diagnosis.

Molecular Pathogenesis

It has been proposed that pancreatic cancer develops from small intraductal precursor lesions (pancreatic intraepithelial neoplasia), following an evolution similar to the adenoma–carcinoma sequence seen in colorectal tumors. Although the precise mechanism and sequence of genetic mutations responsible for the development of pancreatic cancer remains unclear, genetic alterations found in these tumors can be classified into three categories: (1) activation of oncogenes; (2) inactivation of tumor suppressor genes; and (3) defect in DNA mismatch repair genes. The sonic hedgehog signaling pathway also appears to play a role. The sonic hedgehog gene, which is involved with embryonic development, appears to be unregulated in early and late stages of pancreatic carcinogenesis.

Activation of Oncogenes

Mutations of the K-ras oncogene are seen in 90% of tumors and are ...