My Clinical Notes

• Accounts for 5% of all cancer deaths in the UK
• More common in men aged >60
• 5 year survival rate is less than 5%

 

Associations are;

• Smoking (strongest environmental influence)
• High fat/carbohydrate diet
• Diabetes
• Chronic pancreatitis

 

Pathogenesis

• Histologically it is an infiltrating ductal adenocarcinoma
• There are non-invasive precursor lesions of carcinoma called, ‘pancreatic intraepithelial neoplasias’
• There is a progression model for the development of pancreatic cancer associated with a sequence of genetic mutations
• Early mutations in carcinogenesis are;
  • K-ras – oncogene, mutated in 90% of cancers
• Intermediate stage changes are mutations in;
  • p16 – TSG
• Late mutations include;
  • p53
  • SMAD4 – TSG
  • BRCA2 – TSG
• Other genetic alterations are hypermethylation of TSG promoters and amplification of other genes

 

Morphology

• Distribution;
  • 60% occur in the head
  • 15% occur in the body
  • 5% occur in the tail
  • 20% diffuse or widely spread
• Macroscopically they are grey, gritty, hard nodules that are generally invading the gland and local structures
• There are 2 features characteristic of pancreatic carcinoma;
  • Highly infiltrative
  • The elicitation of a nonneoplastic host reaction composed of fibroblasts, lymphocytes and ECM – desmoplastic or fibrous response
• They can be small or larger, more likely to be small if they affect the head so are more likely to impinge on the bile duct causing jaundice and hence be picked up sooner
• They are generally ill-defined
• Microscopically they are generally moderately defined adenocarcinomas composed of glandular spaces in a fibrous stroma
• Less common histological types are;
  • Acinar cell carcinoma
  • Adenosquamous carcinoma
  • Undifferentiated carcinoma composed of osteoclast-like giant cells
• Routes of spread;
  • Locally e.g. into the bile duct or duodenum
  • Lymphatically with spread to the local lymph nodes
  • Haematologically to the liver
• Distant mets can occur, most commonly to the lungs and bones

 

Clinical

• Remain silent until their extension impinges on some other structure
• Typical presenting features are weight loss and pain
• Obstructive jaundice can develop in cancers of the head of the pancreas
• Obstructive jaundice with a painless palpable gallbladder – Courvoisier’s sign
• Migratory thrombophlebitis; development of multiple thromboses in the superficical and deep leg veins – Trousseau’s sign. Due to platelet aggregating and procoagulants being produced by the tumour
• Diabetes due to destruction of the islets of Langerhans
• 85% have metastasised at presentation and are unresectable

 

Management

• Curative resection – Whipple’s procedure, rarely possible in extensive disease
• Palliative surgery – performed to relieved bile duct or duodenal obstruction

This entry was posted on Wednesday, March 5th, 2008 at 5:03 pm and is filed under Biliary tree and pancreas. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.