Background Information
Histology
The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (~85-95%) [Ref]
Causes and Risk Factors
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 |
|
| Local symptoms |
|
| Paraneoplastic manifestation |
|
| Metastatic disease |
|
The most stereotypical presentation is painless jaundice + constitutional symptoms in an older adult.
Diagnosis
Red Flags and Referral
Refer via a suspected cancer pathway if:
- >40 y/o, and
- Jaundice is present
Consider an urgent (within 2 weeks) CT scan (alternative: ultrasound) if:
- >60 y/o, and
- Weight loss is present, and
- ANY of the following
- New-onset diabetes
- Abdominal pain / back pain
- Nausea / vomiting
- Constipation / diarrhoea
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
Management depends on whether the cancer is resectable or not. The 2 core criteria for resectable pancreatic cancer are: [Ref]
- No metastasis
- No local peripancreatic vessel involvement / invasion
Resectable Disease
Definitive management: surgical resection followed by adjuvant chemotherapy (to reduce risk of recurrence)
Choice of resection:
- Pancreatic head cancer
- Standard surgery: Whipple’s resection (pancreatoduodenectomy – resection of the pancreatic head, duodenum, gallbladder, distal common bile duct, and distal stomach, including the pylorus)
- Pylorus-preserving resection should be performed if the tumour can be adequately resected
- Pancreatic cancer affecting the body or tail
- Distal pancreatectomy +/- splenectomy
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.
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