Pancreatic cancer

Overview

Pancreatic cancer is the fifth most common cancer in the UK (~9,000/year), with an overall 5-year survival <5%. ~85-90% are ductal adenocarcinomas; ~70% arise in the head of the pancreas. Most patients present with advanced, unresectable disease - only 15-20% are resectable at diagnosis.

Risk factors

Smoking - strongest modifiable risk factor

Chronic pancreatitis

Type 2 diabetes mellitus

Obesity

Age >60 years

Family history / BRCA2 mutation

Alcohol excess

New-onset diabetes in elderly

Presentation

•Head of pancreas (most common) - painless obstructive jaundice, dark urine, pale stools, pruritus, steatorrhoea

•Courvoisier's sign - painless jaundice + smooth, palpable, non-tender gallbladder = malignant obstruction (gallstones cause fibrosis → impalpable gallbladder)

•Body/tail tumours - new-onset diabetes in an elderly patient with weight loss, severe back pain (coeliac plexus invasion), unexplained pancreatitis

•Non-specific early features - profound unintentional weight loss, anorexia, malaise, epigastric/back pain (worse lying flat, better leaning forward)

•Advanced disease - Trousseau's syndrome (migratory superficial thrombophlebitis), hepatomegaly, ascites

💡

Courvoisier's law: painless jaundice + palpable gallbladder = malignant biliary obstruction until proven otherwise. Gallstones cause chronic inflammation and fibrosis, so the gallbladder cannot distend.

Investigations

•NICE 2-week-wait: age ≥40 with jaundice → direct referral; age ≥60 with unexplained weight loss + diarrhoea/back pain/abdominal pain/nausea/vomiting/new-onset diabetes → urgent CT within 2 weeks

🥇 First-line

•abdominal ultrasound - detects tumours >2 cm, dilated biliary tree, liver metastases, gallbladder distension; LFTs (obstructive pattern: raised bilirubin, ALP, GGT)

🏆 Gold standard

•triple-phase CT abdomen and pelvis - tumour size, vascular involvement (SMA, coeliac axis, portal vein), lymph nodes, metastases; determines resectability

🥈 Second-line

•MRCP - biliary/pancreatic ductal anatomy, identifies double duct sign; EUS - detects lesions down to 2-3 mm, enables tissue biopsy; ERCP - diagnosis + therapeutic biliary stenting for jaundice

•CA19-9 - not diagnostic; used to monitor treatment response and detect recurrence after resection

🎯

Double duct sign (on MRCP or CT) = simultaneous dilatation of the common bile duct AND main pancreatic duct, caused by a tumour at the head of pancreas obstructing both at the ampulla of Vater. Highly suspicious for malignancy.

Management

•Resectable disease (15-20%): Whipple's procedure (pancreaticoduodenectomy) for head of pancreas tumours; distal pancreatectomy for body/tail; followed by adjuvant chemotherapy

•Borderline/locally advanced: neoadjuvant chemotherapy ± radiotherapy to downstage prior to potential resection

•Metastatic/unresectable: palliative chemotherapy (gemcitabine-based); biliary stenting via ERCP for obstructive jaundice; coeliac plexus block for pain

•Supportive: pancreatic enzyme replacement therapy (PERT) for exocrine insufficiency; insulin for diabetes; VTE prophylaxis

Complications

•Obstructive jaundice - secondary cholangitis if bile infected

•Pancreatic exocrine insufficiency - steatorrhoea, fat-soluble vitamin deficiency (A, D, E, K)

•VTE - Trousseau's syndrome, portal/splenic vein thrombosis

•Gastric outlet obstruction - from local invasion of duodenum

•Post-Whipple's - delayed gastric emptying, pancreatic fistula, dumping syndrome

Prognosis

•Overall 5-year survival <5% - driven by late presentation and early metastatic spread

•Surgical resection improves 5-year survival significantly but is only possible in ~15-20%

•Poor chemotherapy response due to dense desmoplastic stroma limiting drug delivery