# Pancreatic Cancer

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**Course:** [Hepatobiliary Medicine: UKMLA](https://medexcellence.co.uk/courses/hepatobiliary-medicine)  
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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   Genetic mutations develop within pancreatic ductal epithelial cells.  Premalignant lesions (PanIN) progressively accumulate further mutations.  Malignant transformation results in pancreatic ductal adenocarcinoma.  The tumour invades surrounding pancreatic tissue.  Local invasion affects the common bile duct, duodenum and major blood vessels.  Lymphatic and haematogenous spread occur early.  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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