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Pancreatic Cancer: Epidemiology, Genetics, and Approaches to Screening

Pancreatic Cancer: Epidemiology, Genetics, and Approaches to Screening

Drs. Konner and O’Reilly have
provided a thorough review of current perspectives on pancreatic cancer. The disease is lethal, difficult
to diagnose in its early stages, and resistant to standard chemotherapy
regimens. Surgery can be curative if performed when the tumor is small (< 2
cm), but only a minority of patients have small tumors.

Research Issues

Over the past 100 years, little headway has been made in understanding the
natural history of the disease or in strategies for its early diagnosis and
treatment. Among the reasons for this lack of progress: (1) the pancreas is
located in a remote region of the body, so that early diagnosis is problematic;
(2) there have been few good animal models of the disease; (3) pancreatic tissue
is difficult to obtain, as most patients do not undergo surgery; (4) the cancer
is rapidly lethal, and thus, it is difficult to quickly recruit patients for
epidemiologic studies and chemotherapy trials; and (5) funding for research in
pancreatic cancer has been limited, averaging $300/cancer diagnosis in the
United States.

Nevertheless, this is an exciting time to be involved in pancreatic cancer
research, as the developments of the past 5 years and the next 10 years will
combine to provide dramatic breakthroughs in our understanding and treatment of
the disease. Our insight into its natural history is increasing significantly.
Pancreatic dysplasia, or pancreatic intraductal neoplasia, is clearly the
precursor to the disease.[1] Patients who had dysplasia at partial
pancreatectomy can develop cancer in the remaining organ 18 months to 10 years
later.[2] Dysplasia shares the same genetic-mutation signatures as the cancer,
and the stepwise histologic progression can be associated with the progression
of molecular defects.

Screening Considerations

Dysplasia appears to occur first in the small and medium-size ducts and, at
least in the familial syndromes, can be multifocal or widespread. This has
implications for screening protocols: Computed tomography (CT) scans cannot
assess changes in the small and medium-size ducts and thus are not helpful for
very early diagnosis or screening.

Endoscopic ultrasound, however, is suitable for detecting early changes in
the pancreatic parenchyma. These changes are similar to those seen in chronic
pancreatitis, and in patients at high risk for cancer and no previous history of
pancreatitis, they can be a marker of neoplastic change.[3] Moreover, endoscopic
ultrasound is cost-effective in patients who have at least a 16% chance of
developing the disease—thus, it would be useful for screening of high-risk
patients with a strong family history.[4] The modality, however, is
operator-dependent, and should be performed in centers with expertise in the
early diagnosis of pancreatic cancer.

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