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.
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. Patients who had dysplasia at partial pancreatectomy can develop cancer in the remaining organ 18 months to 10 years later. Dysplasia shares the same genetic-mutation signatures as the cancer, and the stepwise histologic progression can be associated with the progression of molecular defects.
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. Moreover, endoscopic ultrasound is cost-effective in patients who have at least a 16% chance of developing the diseasethus, it would be useful for screening of high-risk patients with a strong family history. The modality, however, is operator-dependent, and should be performed in centers with expertise in the early diagnosis of pancreatic cancer.