Pancreatic Cancer
Summary
Pancreatic Cancer (PDAC) is the 4th leading cause of cancer death but has the lowest survival rate of all common cancers (5-year survival less than 7%). It is typically an aggressive Ductal Adenocarcinoma arising from the head (60-70%) or body/tail of the pancreas. Because the pancreas is retroperitoneal and lacks a sensory capsule, tumors grow large before causing symptoms. By the time of diagnosis, 80% of patients have unresectable (locally advanced or metastatic) disease. Urgent referral for "Painless Jaundice" or unexplained weight loss >60 is critical. [1,2]
Key Facts
- Courvoisier's Law: In the presence of painless obstructive jaundice, a palpable gallbladder is unlikely to be due to stones (stones cause fibrosis, shrinking the GB). It is Malignancy until proven otherwise.
- Diabetes Link: New onset Type 2 Diabetes in a slim patient >60 years is a major red flag for pancreatic cancer (specifically cancer of the body/tail destroying islet cells).
- Double Duct Sign: Dilatation of both the Common Bile Duct (CBD) and the Pancreatic Duct on imaging. Highly suggestive of a tumour at the Ampulla/Head.
Clinical Pearls
The "Silent" Tail: Tumours in the Head present "early" with jaundice (by blocking the bile duct). Tumours in the Body/Tail do not block the duct; they grow silently until they invade the coeliac plexus nerves, causing excruciating back pain. By then, it is too late.
Depression: Unexplained severe depression often precedes the physical diagnosis of pancreatic cancer by months (paraneoplastic phenomenon?).
CA 19-9: This marker is NOT diagnostic (it is raised in cholangitis/stones). However, a level >1000 virtually confirms malignancy. It is invaluable for monitoring response to chemotherapy.
Risk Factors
- Smoking: The strongest environmental risk factor (2-3x risk).
- Age: Rare under 40. Peak 70-80.
- Chronic Pancreatitis: Alcohol or hereditary.
- Obesity / Diabetes.
- Genetics: BRCA2, Lynch Syndrome, FAMMM.
Anatomy
- Head: Obstructs CBD -> Jaundice. Obstructs Duodenum -> Vomiting (Gastric Outlet Obstruction).
- Body/Tail: Invades Coeliac Plexus -> Back pain. Splenic Vein Thrombosis -> Splenomegaly/Varices.
Genetics
- KRAS: Mutation in >90% of tumours.
- p53: Inactivated in >70%.
Symptoms
Trousseau's Sign
- Jaundice: Scleral icterus. Scratch marks.
- Abdomen: Palpable mass (Head). Palpable Gallbladder (Courvoisier).
- Nodes: Virchow's Node (Left supraclavicular - "Troisier's sign"). Sister Mary Joseph Nodule (Umbilical).
Imaging
- CT Pancreas (Triple Phase): Gold Standard.
- Arterial phase: Pancreas enhances, tumour remains hypodense.
- Assessment: Vessel involvement (SMA/SMV) determines resectability.
- Ultrasound: Poor sensitivity (gas obscures view). Useful first line for biliary dilatation.
- EUS (Endoscopic Ultrasound): Most sensitive for small tumours (less than 2cm). Allows FNA biopsy.
Bloods
- LFTs: Obstructive picture (High Bilirubin, High ALP/GGT).
- CA 19-9: Sensitivity 80%. False negatives in Lewis-negative blood groups (5-10% of population).
Management Algorithm
SUSPECTED PANCREATIC CA
(Jaundice / Weight Loss)
↓
CT PANCREAS PROTOCOL
↓
┌─────────────┼─────────────┐
RESECTABLE BORDERLINE METASTATIC
(No vessel (Abuts vessel) (Liver/Lung)
invasion) ↓ ↓
↓ Neoadjuvant SYSTEMIC
SURGERY Chemo? PALLIATIVE
(Whipple's) ↓ CHEMOTHERAPY
+ Restage
Adjuvant Chemo
1. Surgical (Curative Intent)
Only 15-20% of patients are candidates.
- Whipple's Procedure (Pancreatoduodenectomy):
- Removal of Head, Duodenum, Gallbladder, distal Bile Duct.
- Reconstruction: Pancreaticojejunostomy, Hepaticojejunostomy, Gastrojejunostomy.
- Morbidity: High (Pancreatic fistula, delayed gastric emptying).
- Distal Pancreatectomy: For body/tail tumours. Often involves Splenectomy.
2. Chemotherapy
- FOLFIRINOX: (Fluorouracil, Irinotecan, Oxaliplatin). Very toxic, but best survival data. For fit patients.
- Gemcitabine + Capecitabine: For older/frailer patients. (ESPAC-4 Trial).
- Nab-Paclitaxel: Added to Gemcitabine.
3. Palliative and Symptomatic
- Jaundice: ERCP with Metal Stent deployment. (Relieves itching).
- Enzymes: Creon (Pancreatic Enzyme Replacement Therapy - PERT) for all patients to improve nutrition.
- Pain: Coeliac Plexus Block.
- Gastric Outlet Obstruction (GOO): Tumour compresses duodenum. Persistent vomiting. Needs stent or bypass surgery.
- Ascites: Peritoneal carcinomatosis.
- Depression/Anxiety.
- Overall: 5-year survival 7%.
- Resected: 5-year survival 25-30%.
- Metastatic: Median survival 6 months.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| NG85 | NICE (2018) | Offer PERT (Creon) to everyone. Urgent CT (not US) for suspects. FOLFIRINOX first line for metastatic. |
| Referral | NICE CKS | Refer "Painless Jaundice" via 2-week-wait. Refer "New Diabetes + Weight Loss" via 2WW. |
Landmark Trials
1. ESPAC-4 (2017)
- Findings: Adjuvant Gemcitabine + Capecitabine is superior to Gemcitabine alone. Standard of care post-Whipple.
2. PRODIGE 4 / ACCORD 11
- Findings: FOLFIRINOX superior to Gemcitabine in metastatic disease (Survival 11.1 vs 6.8 months).
Why is it called the Silent Killer?
The pancreas is tucked deep in the back of the tummy. Cancers there can grow quite large without pressing on anything painful. By the time they cause symptoms (like yellow skin or back pain), they have often spread.
What is the Whipple's operation?
It is huge surgery. We remove the head of the pancreas, the gallbladder, the bile duct, and part of the stomach/gut. We then have to "plumb" everything back together. It takes 6-8 hours.
Why do I need enzymes (Creon)?
The cancer blocks the pancreas from releasing juices that digest food. Without them, food goes straight through you (weight loss and floating stools). Taking these capsules with every meal does the digestion for you.
Primary Sources
- NICE Guideline NG85. Pancreatic cancer in adults: diagnosis and management. 2018.
- Neoptolemos JP, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4). Lancet. 2017.
- Conroy T, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011.
Common Exam Questions
- Surgery: "Patient with painless jaundice and palpable gallbladder. Diagnosis?"
- Answer: Ca Head of Pancreas (Courvoisier's Law).
- Radiology: "Double Duct Sign?"
- Answer: Dilated CBD + Dilated Pancreatic Duct.
- Oncology: "Tumour Marker?"
- Answer: CA 19-9.
- Pharmacology: "Best chemo regimen for fit patient?"
- Answer: FOLFIRINOX.
Viva Points
- FOLFIRINOX vs Gemcitabine: FOLFIRINOX is a "bazooka" - very effective but kills immunity (neutropenic sepsis risk). Gemcitabine is "gentle" - well tolerated but less effective. Choice depends on "Performance Status" (PS).
- Lewis Antigen: Why is CA 19-9 negative in some people? CA 19-9 is related to the Lewis blood group antigen. 5-10% of population are Lewis a- b- (null). They cannot make CA 19-9 even if they have a huge tumour.
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