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Pancreatic Cancer

NICE guideline [NG85] Pancreatic cancer in adults: diagnosis and management. Published: Feb 2018.

Background Information

Histology

The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (~85-95%) [Ref]

Aetiology

Key risk factors: [Ref1][Ref2]

  • Modifiable risk factors
    • Smoking – leading risk factor
    • Heavy alcohol consumption
    • Obesity
    • Diabetes
  • Chronic pancreatitis – strong risk factor
  • Genetic predisposition
    • Hereditary pancreatitis (PRSS1 mutation)
    • High-risk mutations (esp. BRCA1 and BRCA2, PALB2, CDKN2A p16)
    • Peutz-Jeghers syndrome (STK11 / LKB1 mutation)
    • Lynch syndrome / hereditary nonpolyposis colorectal cancer (MLH1, MSH2, MSH6, PMS2 mutation)

Clinical Features

Initial symptoms of pancreatic cancer are typically vague and non-specific, resulting in late-stage presentation in the majority of patients:

  • ~50% patients have metastatic disease
  • 30-35% patients have locally advanced, unresectable disease
  • Only 10-20% patients present with localised resectable tumours

The majority of cases (~60–70%) arise in the head of the pancreas. Tumours in this location frequently present with biliary obstruction symptoms. [Ref1][Ref2]

 

The clinical presentation of pancreatic cancer can be grouped into the following: [Ref1][Ref2]

Group Clinical features
Constitutional symptoms
  • Weight loss
  • Anorexia and early satiety
  • Fatigue
  • Cachexia
Local symptoms
  • Abdominal pain +/- back pain (typically mild and vague)
  • Features of biliary obstruction
    • Courvoisier’s law (painless jaundice with palpable gallbladder)
    • Dark urine
    • Pruritus
    • Steatorrhoea (from pancreatic duct obstruction)
Paraneoplastic manifestation
  • Trousseau syndrome (recurrent migratory superficial thrombophlebitis) – classically associated with pancreatic cancer
  • Unprovoked thrombosis
Metastatic disease
  • Hepatomegaly
  • Ascites
  • Lymphadenopathy

The most stereotypical presentation is painless jaundice + constitutional symptoms in an older adult.

Diagnosis

Investigation and Diagnosis

Initial test: abdominal ultrasound

  • Ultrasound is the initial investigation of choice for jaundice when biliary tree pathology is suspected
  • Ultrasound can detect biliary tree dilatation, stones, and masses

 

Diagnostic tests:

  • 1st line: CT abdomen (pancreas protocol)
    • Classic sign: double-duct sign (dilation of the common bile duct and pancreatic duct due to the mass effect of a pancreatic head tumour)
  • 2nd line tests:
    • PET/CT
    • Endoscopic ultrasound with ultrasound-guided biopsy

 

Perform staging with PET / CT.

Serum CA 19-9 is the biomarker of choice for pancreatic cancer, but it’s only useful for monitoring disease, NOT for screening or diagnosis due to poor sensitivity and specificity.

Management

Definitive Management

Interestingly, NICE did not define resectable vs unresectable disease. The literature generally defines resectable pancreatic cancer as:

  • No distant metastases, and
  • No involvement of major peripancreatic arteries or veins

Resectable Disease

Definitive management: surgical resection

  • Standard surgery: Whipple’s resection (resection of the pancreatic head, duodenum, gallbladder, distal common bile duct, and  distal stomach, including the pylorus)
  • Pylorus-preserving resection if the tumour can be adequately resected

 

Offer adjuvant chemotherapy to ALL patients after resection to reduce the risk of recurrence (neo-adjuvant chemotherapy is not routinely recommended).

Unresectable Disease

Definitive management: chemotherapy

  • 1st line: FOLFIRINOX
  • 2nd line: gemcitabine

 

Offer pancreatic enzyme replacement therapy for those with unresectable pancreatic cancer.

It is more than sufficient to be aware that unresectable disease is managed by chemotherapy. It would be unnecessary to memorise the chemotherapy regimens and recommendations.

Management of Complications

Pain Management

Manage as per the WHO pain ladder

 

Consider imaging-guided coeliac plexus block in those with pain that is poorly controlled with standard analgesics.

Biliary Obstruction Management

If the cancer is resectable and suitable → offer resectional surgery (instead of pre-op biliary drainage)

 

If not resectable:

  • Endoscopic biliary stenting
  • Surgical biliary bypass (if cancer is found to be unresectable intraoperatively)

Duodenal Obstruction Management

If the cancer is resectable and suitable → offer resectional surgery

 

If not resectable:

  • Gastrojejunostomy – more favourable prognosis
  • Duodenal stent placement

Reference

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