Early detection and prevention of pancreatic cancer: is it really possible today?

Abstract

Pancreatic cancer is the 4(th) leading cause of cancer-related death in Western countries. Considering the low incidence of pancreatic cancer, population-based screening is not feasible. However, the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well established. In particular, individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5- to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic cancer. The aim of such a program is to reduce pancreatic cancer mortality through early or preemptive surgery. Considering the risk associated with pancreatic surgery, the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals, but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms, or early cancer. Currently, results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions, nor do they define the outcome of the surgical treatment of these lesions. For this reason, surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical trial. However, the acquisition of a deeper understanding of this complex area, together with the increasing request for screening and treatment by individuals at risk, will usher pancreatologists into a new era of preemptive pancreatic surgery. Along with the growing demand to treat individuals with precancerous lesions, the need for low-risk investigation, low-morbidity operation and a minimally invasive approach becomes increasingly pressing. All of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.

Keywords: Cystic tumors of the pancreas; Early detection; Familial pancreatic cancer; Pancreas cancer screening; Preemptive pancreatic surgery.

Figure 1

Intraductal papillary mucinous neoplasia. A: The main pancreatic duct (dotted arrow) and a cluster of branch ducts (arrows) are dilated, and particularly the latter contain mucus and a papillary proliferation on the duct walls (asterisk, common bile duct); B: Partial involvement of a pancreatic branch duct by the papillary proliferation of neoplastic epithelium characteristic of intraductal papillary mucinous neoplasia (HE, 20 × magnification).

Figure 2

Pancreatic intraepithelial neoplasia. Small pancreatic branch ducts are involved by a low-papillary proliferation of neoplastic columnar epithelium showing mild, moderate and severe dysplasia corresponding to pancreatic intraepithelial neoplasia (PanIN)-1, PanIN-2 and PanIN-3.

Figure 3

Lobulocentric atrophy. A: Lobules of acinar parenchyma are atrophic (asterisk) and partially replaced by tubular structures (so-called acinar to ductal metaplasia; dotted arrow) and fibrosis. Note the foci of PanIN-1 in the centre of the changes (arrows); B: Lobulocentric atrophy of neighbouring lobules (asterisk) results in a large area of fibrosis with tubular structures (dotted arrows) but without PanIN-lesion.

Figure 4

Algorithm that combines the current European and international guidelines for intraductal papillary mucinous neoplasia of the pancreas. FNA: Fine needle aspiration; MPD: Main pancreatic duct; EUS: Endoscopic ultrasound. Risk factors¹: Mural nodules, increased serum levels of Ca 19.9, rapid increase in size.