Liver and pancreatic tumours

Liver tumours: what is common

• Commonest malignant tumour in the liver: metastases (colorectal most often, then stomach, pancreas, breast, lung), arriving by the portal vein from the gut or the hepatic artery from elsewhere. Uveal (choroidal) melanoma characteristically metastasises to the liver.
• Commonest primary malignant liver tumour: hepatocellular carcinoma in adults; hepatoblastoma in young children (raised AFP).

Hepatocellular carcinoma

• About 80–90% arise in a cirrhotic liver, because repeated necrosis and regeneration in a hostile environment lets mutations accumulate.
• Hepatitis B can cause HCC without cirrhosis: HBV is a DNA virus whose genome integrates into host DNA, causing insertional mutagenesis and genomic instability, and its HBx protein activates growth signals and interferes with p53. Hepatitis C, an RNA virus that does not integrate, causes HCC almost only through cirrhosis.
• Other causes: alcohol, NAFLD and NASH, aflatoxin B1 (*Aspergillus flavus* on stored grain and nuts; causes a characteristic p53 codon 249 mutation and acts with HBV), haemochromatosis, alpha-1 antitrypsin deficiency, tyrosinaemia. In Pakistan hepatitis C (unsafe injections) and B dominate.
• Presentation: decompensation of known cirrhosis, right upper quadrant pain, weight loss, enlarged tender liver with a bruit, bloody ascites, portal vein invasion with variceal bleeding, rupture. Paraneoplastic: polycythaemia (erythropoietin), hypoglycaemia, hypercalcaemia.
• Tumour marker: alpha-fetoprotein (AFP), used to support diagnosis, surveillance and monitoring. It is raised in many but not all HCCs, and also in yolk sac tumours, hepatoblastoma and pregnancy. A rising AFP in a hepatitis B carrier or alcoholic with a liver mass suggests HCC. (Low maternal serum AFP with low oestriol in pregnancy points to Down syndrome, a different use of the same protein.)
• Surveillance: ultrasound every 6 months, with or without AFP, in cirrhosis and high-risk HBV carriers.
• Diagnosis: in a cirrhotic liver, multiphase CT or MRI showing arterial phase hyperenhancement with washout in the portal venous or delayed phase is diagnostic without biopsy. Biopsy is reserved for atypical imaging or a lesion in a non-cirrhotic liver.
• Treatment by BCLC stage: resection (single tumour, good liver function, no portal hypertension); transplantation within Milan criteria (one tumour up to 5 cm, or up to three each up to 3 cm, no vascular invasion or spread); radiofrequency or microwave ablation for small tumours; TACE for intermediate stage (HCC takes its blood from the hepatic artery, so embolising the artery starves the tumour while the portal vein keeps the liver alive); systemic therapy (atezolizumab with bevacizumab, sorafenib, lenvatinib).
• Fibrolamellar carcinoma: young adults, no cirrhosis, normal AFP, better prognosis.
• Prevention: hepatitis B vaccination, treating HCV, safe injections and blood products.

Cholangiocarcinoma

• Adenocarcinoma of the bile ducts: intrahepatic, perihilar (Klatskin tumour, at the hepatic duct confluence; commonest), or distal.
• Risk factors share one theme, chronic biliary inflammation: primary sclerosing cholangitis (with ulcerative colitis), liver flukes *Clonorchis sinensis* and *Opisthorchis*, choledochal cysts, hepatolithiasis, Caroli disease, thorotrast. Hydatid cyst is not a recognised cause.
• Painless progressive obstructive jaundice, pruritus, weight loss. A perihilar tumour blocks above the cystic duct, so the gallbladder is not palpable. Markers CA 19-9 and CEA; MRCP and CT; ERCP brushings.

Gallbladder cancer

• High incidence in northern India and Pakistan, mainly in women. Gallstones (large, long-standing) cause it through chronic mucosal irritation and inflammation leading to dysplasia. Other risks: porcelain gallbladder, polyps over 1 cm, chronic typhoid carriage, anomalous pancreaticobiliary junction.
• Often found incidentally after cholecystectomy or presents late with a mass and jaundice.
• The gallbladder bed lies against liver segments IVb and V, so tumour invading the liver spreads there first and radical cholecystectomy removes these segments with the regional nodes. Incidental tumours of T1b or deeper need re-resection of the bed.

Pancreatic cancer

• Ductal adenocarcinoma (about 90%); two-thirds in the head. KRAS mutation in more than 90%, with CDKN2A, TP53 and SMAD4.
• Risks: smoking (strongest modifiable), chronic pancreatitis, new diabetes in older adults, obesity, family history, BRCA2, Peutz–Jeghers, hereditary pancreatitis, Lynch syndrome. Precursors: PanIN, IPMN, mucinous cystic neoplasm.

• Courvoisier law: with painless jaundice, a palpable gallbladder is unlikely to be due to stones, because a stone-bearing gallbladder is chronically scarred and cannot distend.
• Pancreatic protocol CT is the investigation of choice (diagnosis, staging, resectability); EUS-guided FNA gives tissue; CA 19-9 for prognosis and follow-up (also raised by benign obstruction; absent in Lewis-negative people).
• Only about 15–20% are resectable. Whipple pancreaticoduodenectomy for head and periampullary tumours (pancreatic fistula, delayed gastric emptying); distal pancreatectomy with splenectomy for the tail; adjuvant mFOLFIRINOX. Palliation: biliary metal stent, duodenal stent or gastrojejunostomy, coeliac plexus block, enzyme replacement.
• Periampullary tumours present earlier, sometimes with intermittent jaundice and silver stool, and do better.

Pancreatic neuroendocrine tumours

• MEN 1 (menin): parathyroid hyperplasia (commonest feature), pancreatic NETs, pituitary adenoma.

Remember Metastases are the commonest liver malignancy; haemangioma the commonest benign lesion; HCC the commonest primary malignancy in adults.

Exam trap Never biopsy a suspected haemangioma; peripheral nodular enhancement with centripetal fill-in is diagnostic.

Exam trap Courvoisier law: painless jaundice with a palpable gallbladder means malignant obstruction, usually the pancreatic head.

How FCPS asks about this

• Tumour marker to screen and monitor HCC in cirrhosis: alpha-fetoprotein with 6-monthly ultrasound.
• Why hepatitis B causes HCC without cirrhosis: viral DNA integration and the HBx protein.
• Peripheral nodular enhancement filling in centrally: cavernous haemangioma; do not biopsy.
• Confirming HCC in cirrhosis: multiphase CT or MRI with arterial enhancement and washout; biopsy only if atypical.
• Organism causing cholangiocarcinoma: *Clonorchis sinensis*; PSC with ulcerative colitis is the other classic cause.
• Painless jaundice with palpable gallbladder: carcinoma of the pancreatic head (Courvoisier law); CT is the investigation of choice.
• Gallbladder cancer invading the liver: segments IVb and V resected; gallstones act by chronic irritation.