Pancreatic Cancer Screening

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Pancreatic Cancer: Why Consider Screening?

Pancreatic cancer remains one of the most deadly diseases, despite significant advances in medicine over the past decade. Pancreatic adenocarcinoma is the fourth leading cause of cancer deaths in the United States for both males and females, with an estimated 44,030 new cases and 37,660 deaths in 2011.1 In contrast to the death rates for other leading causes of cancer death (lung, colorectal, breast, and prostate), which have declined since 2003, the death rate from pancreatic adenocarcinoma

Genetic Predisposition to Pancreatic Cancer

Although the great majority of pancreatic adenocarcinoma cases are thought to be sporadic in nature, up to 10% of cases can be attributed to genetic factors.2, 3, 4 In fact, familial clustering of pancreatic cancer was noted as early as 1967, when Lynch and colleagues reported on an adenocarcinoma-prone family.5 Familial pancreatic cancer (FPC) is characterized by two or more first-degree relatives (FDRs) with pancreatic adenocarcinoma in the absence of known cancer syndromes or other diseases

Hereditary Pancreatitis

Hereditary pancreatitis is a rare inherited disorder characterized by recurrent attacks of acute pancreatitis in childhood or early adolescence, followed by the development of chronic pancreatitis in late adolescence or early adulthood.26 It is transmitted as an autosomal dominant disorder with incomplete penetrance.27 Most are due to germline gain-of-function mutations in a cationic trypsinogen gene (PRSS1) on chromosome 7q35.28, 29, 30 Mutations in PRSS1 cause premature trypsin activation and

Targets for Screening and Surveillance

The ideal screening strategy for pancreatic cancer would target high-grade benign noninvasive precursor neoplastic lesions (pancreatic intraepithelial neoplasias [PanINs] or intraductal papillary mucinous neoplasms [IPMNs]) before malignant transformation or at an early stage that would allow for curative surgical resection.56 Although IPMNs can be detected as cystic lesions or a dilated main pancreatic duct or both, PanINs are small branch ducts less than 5 mm in size, often microscopic, and

Available and Anticipated Tumor Markers

Currently, there is no biomarker with adequate sensitivity and specificity that can be used for routine clinical screening.57 Given the typical late stage of disease at the time of diagnosis, there has been much effort invested in identifying accurate tumor markers to aid in earlier diagnosis of pancreatic cancer.

The most widely used serum marker in patients with pancreatic cancer is sialylated Lewis blood group antigen on MUC-1 (Mucin 1, cell surface associated), carbohydrate antigen 19-9 (CA

Approaches to Screening

Currently, there is no sufficiently sensitive, specific, and reliable screening test for the early detection of pancreatic cancer. The great majority of pancreatic cancers, accounting for at least 90% of all patients, are considered sporadic.2, 3, 4 The detection rate is low in average-risk individuals because pancreatic cancer is a rare disease, despite its significant death toll. In screening studies performed in Japan, 5 cancers were found in 2511 individuals.114 Given the overall low

Summary

Accumulating data indicate that clinically available abdominal imaging tests such as EUS and MRI/MRCP can detect asymptomatic precursor benign (IPMN, PanIN) and invasive malignant pancreatic neoplasms, such as ductal adenocarcinoma, in individuals with an inherited predisposition. These asymptomatic FPCs detected have been more likely to be resectable, compared to symptomatic tumors. The most challenging part of screening high-risk individuals is the selection of individuals with high-grade

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