Pancreatic cancer

Introduction

Pancreatic cancer is an aggressive malignancy with a poor prognosis due to its late presentation. The most common histological type is adenocarcinoma, which typically arises in the head of the pancreas. As the tumour enlarges, it may obstruct the biliary tract, leading to obstructive jaundice.

Peak Incidence

• Most commonly diagnosed between 85 and 89 years of age.

Risk Factors

• Smoking.
• Obesity.
• Type 2 diabetes mellitus.
• Chronic pancreatitis.
• Age over 60 years.
• Family history of pancreatic cancer, including:
  • BRCA2 or KRAS mutations.
  • Hereditary non-polyposis colorectal cancer (HNPCC).
  • Multiple endocrine neoplasia (MEN) syndromes.

Pathophysiology

• Pancreatic adenocarcinoma often arises from precursor lesions such as pancreatic intraepithelial neoplasia (PanIN).
• Tumour growth can invade adjacent structures (e.g. duodenum, bile duct, vasculature) and metastasise via lymphatic and haematogenous spread.
• Obstruction of the common bile duct is typical for tumours in the head of the pancreas, leading to cholestasis and associated symptoms.

Symptoms

Cholestatic Symptoms

• Painless jaundice.
• Pale stools.
• Dark urine.
• Pruritus.

Endocrine Dysfunction

• New-onset diabetes.
• Worsening glycaemic control in pre-existing diabetes.

Exocrine Dysfunction

• Steatorrhoea – Fatty, foul-smelling stools due to pancreatic enzyme insufficiency.

Other Non-Specific Symptoms

• Anorexia.
• Nausea and vomiting.
• Change in bowel habit.
• Back or epigastric pain.

Signs

• Courvoisier’s sign – A painless, palpable gallbladder with jaundice suggests malignancy rather than gallstones.
• Epigastric mass.
• Trousseau’s sign of malignancy – Migratory thrombophlebitis, often involving superficial veins.
• Hepatomegaly – May indicate liver metastases.

Diagnosis

Referral Criteria (UK Guidelines)

• Urgent 2-week wait referral:
  • Any patient aged >40 years with jaundice.
• Direct access CT abdomen:
  • Patients aged >60 years with weight loss and one or more of the following:
    • Diarrhoea.
    • Back or abdominal pain.
    • Constipation.
    • New-onset diabetes.
    • Nausea or vomiting.

Investigations

• High-resolution CT scan – First-line and gold standard for diagnosis.
  • May show double duct sign (dilated common bile duct and pancreatic duct).
• Ultrasound – To assess for biliary dilation or gallstones.
• MRCP (Magnetic Resonance Cholangiopancreatography) – For non-invasive visualisation of the biliary and pancreatic ducts.
• CA 19-9 – A tumour marker that may be elevated but is not diagnostic.
• Histological confirmation:
  • Via endoscopic ultrasound (EUS)-guided biopsy or percutaneous biopsy.
• CT Thorax, Abdomen, Pelvis (CT TAP) – For staging and assessing metastases.

Complications

• Metastatic spread – Commonly to liver, lungs, peritoneum, or bones.
• Chronic abdominal or back pain.
• Biliary obstruction – Leading to jaundice and cholangitis.
• Exocrine insufficiency – Causing malabsorption and weight loss.
• Thromboembolic events – Including deep vein thrombosis or pulmonary embolism (due to a hypercoagulable state).

Management

Curative Surgery (only possible in ~15–20% of cases)

• Whipple procedure (pancreaticoduodenectomy) – Removal of pancreatic head, duodenum, gallbladder, distal bile duct, and part of the stomach.
• Pylorus-preserving pancreaticoduodenectomy (PPPD) – A variant that preserves the stomach.
• Distal pancreatectomy – Removal of pancreatic body and tail.
• Total pancreatectomy – Rare; involves removing the entire pancreas.

Adjuvant Therapy

• Chemotherapy ± radiotherapy – May improve survival following resection (e.g. gemcitabine or FOLFIRINOX).

Palliative Management

• ERCP with stent placement – To relieve biliary obstruction and jaundice.

• Palliative chemotherapy or radiotherapy – Used for symptom control and to prolong survival in unresectable or metastatic disease.

• Nutritional support – Including pancreatic enzyme replacement if exocrine insufficiency is present.

• Pain management – Often requiring opioids or celiac plexus nerve block.

• End-of-life care – Focused on symptom relief and quality of life.