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Pancreatic Cancer

· Part of Hepatobiliary Medicine: UKMLA

Definition

Pancreatic cancer is a malignant tumour arising from the pancreas, with pancreatic ductal adenocarcinoma accounting for over 90% of cases. It is an aggressive malignancy that often presents late due to non-specific symptoms and carries a poor prognosis.

Pathophysiology

  1. Genetic mutations develop within pancreatic ductal epithelial cells.
  2. Premalignant lesions (PanIN) progressively accumulate further mutations.
  3. Malignant transformation results in pancreatic ductal adenocarcinoma.
  4. The tumour invades surrounding pancreatic tissue.
  5. Local invasion affects the common bile duct, duodenum and major blood vessels.
  6. Lymphatic and haematogenous spread occur early.
  7. Advanced disease commonly metastasises to the liver, peritoneum and lungs.

Types of Pancreatic Cancer

Pancreatic Ductal Adenocarcinoma (Most Common)

  • 90% of pancreatic cancers.

  • Usually arises in the head of the pancreas.

Pancreatic Neuroendocrine Tumours (PNETs)

  • Less common.
  • May be functioning (hormone-producing) or non-functioning.
  • Generally have a better prognosis.

Risk Factors

  • Increasing age (>60 years).
  • Smoking.
  • Chronic pancreatitis.
  • Type 2 diabetes mellitus.
  • Obesity.
  • Family history of pancreatic cancer.
  • BRCA1 or BRCA2 mutations.
  • Peutz-Jeghers syndrome.
  • Lynch syndrome.
  • Hereditary pancreatitis.

Clinical Features

Symptoms

  • Painless jaundice (classically with tumours in the pancreatic head).
  • Epigastric pain radiating to the back.
  • Weight loss.
  • Anorexia.
  • Fatigue.
  • Nausea.
  • Steatorrhoea.
  • New-onset diabetes mellitus.
  • Dark urine.
  • Pale stools.
  • Pruritus.

Signs

  • Jaundice.
  • Palpable non-tender gallbladder (Courvoisier's sign).
  • Cachexia.
  • Epigastric tenderness.
  • Hepatomegaly (liver metastases).
  • Ascites (advanced disease).
  • Left supraclavicular lymphadenopathy (Virchow's node) (rare).
  • Migratory thrombophlebitis (Trousseau syndrome).

Investigations

Blood Tests

FBC

  • Anaemia may be present.

LFTs

  • Cholestatic pattern:
    • Raised bilirubin.
    • Raised ALP.
    • Raised GGT.

U&Es

  • Baseline renal function.

Glucose / HbA1c

  • Assess for diabetes mellitus.

CA 19-9

  • Tumour marker used to monitor treatment response.
  • Not suitable as a screening test.
  • May be normal in early disease.

Imaging

Pancreatic protocol CT (first-line)

  • First-line investigation for diagnosis and staging.
  • Assesses tumour size.
  • Evaluates vascular invasion.
  • Detects metastatic disease.

Abdominal ultrasound

  • May detect biliary dilatation.
  • Often the first investigation in jaundiced patients.

MRI / MRCP

  • Better assessment of biliary and pancreatic ducts.
  • Useful if CT findings are equivocal.

Endoscopic ultrasound (EUS)

  • Highly sensitive for small lesions.
  • Allows fine-needle aspiration (FNA).

ERCP

  • Primarily therapeutic.
  • Allows biliary stent insertion in obstructive jaundice.

Biopsy

  • Histological confirmation before chemotherapy or unresectable disease.
  • Often performed during EUS-guided FNA.

Staging

TNM Staging

Assesses:

  • Tumour size.
  • Nodal involvement.
  • Distant metastases.

Determines resectability and treatment options.

Management

Resectable Disease

Surgical Resection

Tumours in the pancreatic head

  • Pancreaticoduodenectomy (Whipple procedure).

Tumours in the body or tail

  • Distal pancreatectomy ± splenectomy.

Adjuvant Chemotherapy

  • Usually follows surgery.

Borderline or Locally Advanced Disease

  • Neoadjuvant chemotherapy ± radiotherapy.
  • Reassessment for surgery.

Metastatic Disease

  • Systemic chemotherapy.
  • Palliative care.
  • Symptom control.

Supportive Management

Obstructive Jaundice

  • ERCP with biliary stent insertion.

Pain

  • WHO analgesic ladder.
  • Coeliac plexus block if severe.

Pancreatic Exocrine Insufficiency

  • Pancreatic enzyme replacement therapy (PERT).

Nutritional Support

  • Dietitian input.
  • Vitamin supplementation where appropriate.

Complications

Local

  • Biliary obstruction.
  • Gastric outlet obstruction.
  • Pancreatic exocrine insufficiency.

Metastatic

  • Liver metastases.
  • Peritoneal metastases.
  • Lung metastases.

Other

  • Venous thromboembolism.
  • Malnutrition.
  • Diabetes mellitus.
  • Cachexia.

Differential Diagnosis

  • Chronic pancreatitis.
  • Pancreatic pseudocyst.
  • Ampullary carcinoma.
  • Cholangiocarcinoma.
  • Gallstone disease.
  • Autoimmune pancreatitis.
  • Peptic ulcer disease.

UKMLA Key Points

  • Pancreatic ductal adenocarcinoma accounts for over 90% of pancreatic cancers.
  • Painless obstructive jaundice with weight loss should be considered pancreatic cancer until proven otherwise.
  • Courvoisier's sign (painless jaundice with a palpable gallbladder) suggests malignant biliary obstruction rather than gallstones.
  • Pancreatic protocol CT is the first-line investigation for diagnosis and staging.
  • CA 19-9 is useful for monitoring treatment response but is not a screening test.
  • The Whipple procedure is the standard operation for resectable tumours of the pancreatic head.
  • ERCP with biliary stenting relieves obstructive jaundice in unresectable disease or prior to surgery when indicated.
  • Most patients present with advanced disease, making pancreatic cancer one of the malignancies with the poorest overall prognosis.
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