Histological images of benign pancreatic ductal epithelial cells, progressive PanIN lesions and invasive carcinoma, with associated genetic alterations.

 Mitogenic signals give rise to increased levels of cyclin D and the consequent formation of active cyclin D/cyclin-dependent kinase 4 or 6 (CDK4/CDK6) complexes leads to the phosphorylation of retinoblastoma (Rb), facilitating the transcription of E2F-regulated genes (including cyclin E) required for the S-phase. Cyclin E–CDK2 complexes further phosphorylate Rb. The tumour suppressor INK4A gene product interferes with this process by binding to CDK4/CDK6, thus preventing the formation of active cyclin D–CDK4/CDK6 complexes. The tumour suppressor, p53, is activated in response to DNA damage or other cellular stresses. MDM2 is a p53-inducible gene, the protein product of which keeps p53 levels low. The p14ARF protein inhibits MDM2, thus inducing p53. Activated p53 either initiates Rb-dependent cell cycle arrest by inducing the transcription of p21^CIP1, which inhibits cyclin E-CDK2, or leads to apoptosis.

 Contrast-enhanced multidetector CT scan image of pancreatic tumour encasing the hepatic artery (arrow) and obliteration of the portal vein (cross) causing cavernous transformation. This patient is unresectable.

 Contrast-enhanced multidetector CT scan image of a mucinous cystic neoplasm, demonstrating a papillary invagination.

 Schematic representation of molecular oncogenic signalling pathways in pancreatic cancer. Agents targeting specific aspects of these pathways are indicated in blue boxes.

 Contrast-enhanced multidetector CT scan image of a resectable pancreatic adenocarcinoma with acceptable planes of cleavage between the tumour (t) and the superior mesenteric vein (arrow) and the superior mesenteric artery (arrowhead).

 Contrast-enhanced multidetector CT scan image of pancreatic tumour encasing the superior mesenteric artery (arrow). This patient has unresectable disease.

 Coronal section of multidetector CT scan demonstrating pancreatic tumour encasing the portal vein. This patient has unresectable disease.

 Endoluminal ultrasound demonstrating a small pancreatic cancer.

 (A) Contrast-enhanced multidetector CT scan image of a serous cystic neoplasm, demonstrating the characteristic honeycomb appearance. (B) Honeycomb cysts of serous cystic neoplasm are lined by simple cuboidal epithelium with (glycogen-rich) clear cell cytoplasm.

 (A) Endoluminal ultrasonography showing septate mucinous cystic lesion. (B) Simple columnar mucinous epithelial lining of a mucinous cystic neoplasm.

 (A) Contrast-enhanced multidetector CT scan image of a main duct intraductal papillary mucinous neoplasm, demonstrating dilatation of the whole of the main pancreatic duct. (B) High-power view of intraductal papillary mucinous neoplasm, showing minimal atypia within the lining mucinous epithelium.

 (A) Magnetic resonance imaging scan demonstrating a side-branch intraductal papillary mucinous neoplasm. (B) Low-power view of branch-type intraductal papillary mucinous neoplasm, showing papillary infoldings of lining epithelium.