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PA31.{5,7} | Diabetes Mellitus & Pancreatic Cancer — SDL Guide (Part 5)

Clinical Manifestations, Lab Markers, Spread, and Prognosis

Clinical presentation — the 'silent assassin' pattern:

The pancreas is a retroperitoneal organ with no early warning system. Symptoms appear late, usually when the tumour is locally advanced or metastatic.

Head-of-pancreas tumours (60% of cases) — triad of:
1. Painless obstructive jaundice — the most common presenting symptom; caused by compression of the common bile duct; associated with acholic (clay-coloured) stools, dark urine, and pruritus
2. Courvoisier's sign — palpable, non-tender gallbladder in the presence of jaundice; law: "In obstructive jaundice with a palpable gallbladder, the cause is unlikely to be gallstones" (because gallstones → chronic inflammation → fibrotic, non-distensible gallbladder; cancer → gradual duct obstruction → distensible gallbladder)
3. Epigastric/back pain — radiation to the back in a boring quality; due to coeliac plexus invasion; often the sign of unresectability

Body/tail tumours: Present later with vague abdominal pain, weight loss, and jaundice only if metastases involve the liver — smaller tumours are often detected incidentally

Systemic and paraneoplastic features:
- Weight loss and cachexia — almost universal; due to anorexia, malabsorption (pancreatic duct obstruction → exocrine insufficiency → steatorrhoea), and tumour-derived catabolic cytokines
- New-onset DM in an elderly patient without obvious risk factors — 25% of PDAC patients develop DM within 1–3 years of diagnosis; may precede cancer diagnosis by years
- Trousseau's migratory thrombophlebitis — recurrent superficial thrombophlebitis affecting different veins; classic paraneoplastic sign of mucin-secreting adenocarcinomas (PDAC is the prototype); mechanism: tumour mucin activates tissue factor → hypercoagulable state; Trousseau coined this after noticing it in his own gastric cancer
- Depression and anxiety — disproportionate to stage; may precede diagnosis

Laboratory investigations:
- CA19-9 (carbohydrate antigen 19-9, also called sialyl Lewis Aᵃ antigen) — the most useful tumour marker:
- Sensitivity 80–85%, specificity 70–80% for PDAC
- Not diagnostic alone — elevated in biliary obstruction (benign or malignant), pancreatitis, cholangiocarcinoma
- Most useful for monitoring treatment response and recurrence in known PDAC
- Patients who are Lewis blood group negative (10–15% of population) cannot synthesise CA19-9 and will always have undetectable levels regardless of tumour status
- Liver function tests: Elevated bilirubin (conjugated), ALP, GGT, transaminases — obstructive pattern
- CT/MRI: Double duct sign (dilated CBD + main pancreatic duct); vascular encasement (superior mesenteric artery/vein → unresectability); liver metastases

Metastatic spread:
- Lymphatic: Peripancreatic, coeliac, and para-aortic lymph nodes — early, virtually universal
- Perineural: Along nerve sheaths (as above) — explains poor surgical margins
- Haematogenous: Liver (most common site, portal circulation), lungs, peritoneum
- Direct extension: Duodenum, stomach, spleen, superior mesenteric vessels

Prognosis:
- Overall 5-year survival: < 10% (one of the worst of any solid tumour)
- <20% of patients have resectable disease at diagnosis
- After potentially curative pancreatectomy (Whipple procedure): 5-year survival 20–25% (improved with adjuvant chemotherapy)
- Median survival with metastatic disease: 6–12 months
- The grim prognosis reflects: late presentation, early vascular and perineural invasion, desmoplastic stroma (drug-resistant), and lack of effective screening

Courvoisier's Sign — Hepatopancreatic Anatomy, Pathology, and Double Duct Sign