Pancreatic Cancer
Summary
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies, with a 5-year survival rate of less than 5%. It is characterized by early metastasis and late presentation. Tumours of the Head (70%) present earlier with Painless Jaundice (biliary obstruction). Tumours of the Body/Tail (30%) present late with non-specific back pain and weight loss. Radical resection (Whipple's or Distal Pancreatectomy) offers the only chance of cure, but only 10-20% of patients are resectable at diagnosis. [1,2]
Clinical Pearls
Courvoisier's Law: "In the presence of painless jaundice, a palpable gallbladder is unlikely to be due to gallstones."
- Reason: Gallstones cause chronic inflammation and fibrosis, making the gallbladder shrunken and unable to distend. A tumour causes slow, progressive obstruction, allowing the non-scarred gallbladder to dilate hugely.
The "Double Duct" Sign: The pathognomonic finding on CT/MRI. Because the pancreatic head tumour compresses both the Common Bile Duct and the Pancreatic Duct, both are dilated upstream.
Trousseau's Sign of Malignancy: Migratory Thrombophlebitis. Recurrent, unexplained superficial clots in different veins (arms/legs). It reflects the hypercoagulable state induced by mucin-rich pancreatic tumours.
Demographics
- Incidence: 10th most common cancer, but 4th-5th leading cause of cancer death.
- Age: Peak 65-80 years. Rare less than 45.
- Risk Factors:
- Smoking (RR 2.0).
- Chronic Pancreatitis (Alcohol/Hereditary).
- Obesity / Type 2 Diabetes.
- Genetics: BRCA2, Lynch Syndrome, FAMMM (p16).
Molecular Biology
- Driver Mutation: KRAS (>90% of cases).
- Tumour Suppressors: p53, SMAD4, CDKN2A.
- Morphology: Highly desmoplastic (scar-like) stroma, which creates a hypoxic barrier to chemotherapy delivery.
Anatomy of Spread
- Local: Invades Duodenum (GOO), Stomach, Colon, Portal Vein, SMA.
- Lymphatic: Peripancreatic nodes -> Coeliac/Mesenteric.
- Metastatic: Liver (Primary site), Lungs, Peritoneum (Ascites).
Symptoms
- General: Cachexia, Jaundice, Scratch marks (excoriations).
- Abdomen:
- Mass in epigastrium (rarely palpable usually).
- Palpable Gallbladder (RLQ, smooth, non-tender).
- Ascites.
- Hepatomegaly (Mets).
- Nodes: Virchow's Node (Left supraclavicular).
Imaging
- CT Pancreas (Triple Phase): Gold standard.
- Arterial Phase: Assesses SMA involvement.
- Portal Venous Phase: Assesses SMV/Portal Vein involvement and Liver mets.
- MRI/MRCP: To define biliary tree if CT equivocal.
Endoscopy
- EUS (Endoscopic Ultrasound):
- Most sensitive for small tumours (less than 2cm).
- Allows FNA Biopsy for histological confirmation (required for chemotherapy, but not mandatory if proceeding straight to Whipple's in clear-cut cases).
- ERCP: Generally avoids for diagnosis (risk of pancreatitis). Used for stenting only.
Biomarkers
- CA 19-9: Sensitivity ~80%. Elevated in jaundice anyway. Useful for baseline to monitor treatment response.
Management Algorithm
PANCREATIC MASS DETECTED
↓
CT STAGING (Triple Phase)
+ CA 19-9 + CXR
┌─────────┴─────────┐
METASTATIC NON-METASTATIC
(Liver/Lung) (Assess Vessels)
↓ ↓
PALLIATIVE VASCULAR INVASION?
CHEMO NO YES
(FOLFIRINOX) ↓ ↓
RESECTABLE BORDERLINE
↓ ↓
SURGERY NEOADJUVANT
(Whipple) CHEMO
Surgical Options (The Only Cure)
- Whipple's Procedure (Pancreaticoduodenectomy): For Head tumours.
- Resection of: Head of Pancreas + Duodenum + Gallbladder + Distal CBD + Antrum of Stomach.
- Reconstruction: Pancreatico-jejunostomy, Hepatico-jejunostomy, Gastro-jejunostomy.
- Mortality: less than 3% in high volume centres. Morbidity: 40%.
- Distal Pancreatectomy: For Body/Tail tumours. usually involves Splenectomy.
Systemic Therapy
- Adjuvant (Post-op): Standard. FOLFIRINOX (Modified) or Gemcitabine + Capecitabine (ESPAC-4). Improves 5-year survival from ~10% to ~30%.
- Palliative: Gemcitabine is standard for frail patients (tolerable side effects). FOLFIRINOX for fit patients (more toxic but better survival).
Palliative Symptom Control
- Jaundice: ERCP Metal Stent.
- Duodenal Obstruction: Duodenal Stent or Gastro-Jejunostomy bypass.
- Pain: Coeliac Plexus Block (alcohol injection to destroy nerves).
- Steatorrhoea: Creon (Enzyme replacement).
- Exocrine Insufficiency: Malabsorption, fatty stools (Steatorrhoea). Needs Creon.
- Endocrine Insufficiency: Type 3c Diabetes (Pancreatogenic). Tough to manage (brittle).
- Depression: High prevalence in pancreatic cancer (biological basis?).
- Overall: Dismal. Most die within 1 year.
- Resectable: 20-25% 5-year survival.
- Metastatic: 3-6 months median survival.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Pancreatic Cancer | NICE (NG85) | "Fast Track" pathway for jaundice. |
| Adjuvant Therapy | ASCO | FOLFIRINOX as preferred regimen. |
Landmark Evidence
1. ESPAC-4 Trial (Lancet 2017)
- Showed the combination of Gemcitabine + Capecitabine was superior to Gemcitabine alone in the adjuvant setting.
2. PRODIGE 24 (NEJM 2018)
- Showed mFOLFIRINOX was significantly superior to Gemcitabine in adjuvant setting (Median survival 54 months vs 35 months). This set the new gold standard for fit patients.
What is Pancreatic Cancer?
It is a cancer of the gland that sits behind your stomach, which helps digest food and control sugar. It is notorious for growing silently and unrelated to pain until it is quite large.
Why have I turned yellow?
The pancreas head sits right next to the bile duct (the pipe that drains waste from the liver). The tumour is squeezing this pipe shut, so the yellow bile backs up into your blood and skin.
Can you operate?
We simulate the operation on a CT scan first. If the tumour is wrapped around the major blood vessels that feed the liver and bowel (which run right behind the pancreas), we cannot safely remove it. If it is clear of the vessels, we offer a major operation called a Whipple's to remove the cancer.
What if you can't operate?
We can still treat it. We use chemotherapy to shrink the tumour and slow it down. We can also put a small metal tube (stent) inside the blocked bile duct using a camera down the throat to open it up and cure the jaundice/itching.
Primary Sources
- Conroy T, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer (PRODIGE 24). N Engl J Med. 2018.
- Neoptolemos JP, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4). Lancet. 2017.
- NICE NG85. Pancreatic cancer in adults: diagnosis and management. 2018.
Common Exam Questions
- Sign: "Painless jaundice + Palpable Gallbladder?"
- Answer: Courvoisier's Law (Pancreatic Head CA).
- Imaging: "Dilated CBD and Pancreatic Duct?"
- Answer: Double Duct Sign.
- Marker: "Tumour Marker for monitoring?"
- Answer: CA 19-9.
- Paraneoplastic: "Migratory Thrombophlebitis?"
- Answer: Trousseau's Sign.
Viva Points
- Why painless jaundice?: Because the obstruction is extrinsic compression, not intraluminal stone impaction (which causes colic/spasm).
- Whipple Anatomy: Be able to list the 3 anastomoses (PJ, HJ, GJ). PJ (Pancreas to Jejunum) is the Achilles heel – it leaks most often.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.