The prevalence of
pancreatic cancer in the general population is too low--even in high-prevalence areas such as Northern Europe and North America (8-12 per 10(5) population)--relative to the diagnostic accuracy of present detection methods to permit primary screening in the asymptomatic adult population. The recognition that the lifetime risk of developing
pancreatic cancer for patients with
hereditary pancreatitis (HP) is extremely high (20% by the age of 60 years and 40% by the age of 70 years) poses considerable challenges and opportunities for secondary screening in those patients without any clinical features of
pancreatic cancer. Even for secondary screening, the detection of
cancer at a
biological stage that would be amenable to cure by surgery (total
pancreatectomy) still requires diagnostic modalities with a very high sensitivity and specificity. Conventional radiological imaging methods such as endoluminal ultrasound and endoscopic retrograde pancreatography, which have proved to be valuable in the early detection of early neoplastic lesions in patients with familial
pancreatic cancer, may well be applicable to patients with HP but only in those without gross morphological features of
chronic pancreatitis (other than parenchymal
atrophy). Unfortunately, most cases of HP also have associated gross features of
chronic pancreatitis that are likely to seriously undermine the diagnostic value of these conventional imaging modalities. Pre-malignant molecular changes can be detected in the pancreatic juice of patients. Thus, the application of molecular screening in patients with HP is potentially the most powerful method of detection of early
pancreatic cancer. Although mutant (mt) K-ras can be detected in the pancreatic juice of most patients with
pancreatic cancer, it is also present in patients with non-inherited
chronic pancreatitis who do not progress to
pancreatic cancer (at least in the short to medium term), as well as increasingly in the older population without
pancreatic disease. Nevertheless, the presence of mt-K-ras may identify a genuinely higher-risk group, enabling additional diagnostic imaging and molecular resources to be focussed on such a group. What is clear is that prospective multi-centre studies, such as that being pursued by the European Registry of
Hereditary Pancreatitis and Familial
Pancreatic Cancer (EUROPAC), are essential for the development of an effective secondary screening programme for these patients.