360.1 🎓 醫孞生版

360.1.0.1 📌 䞀頁重點

360.1.0.1.1 Hepatocellular Carcinoma (HCC)

360.1.1 Epidemiology

  • 6th most common cancer worldwide
  • 3rd leading cause of cancer death
  • ~ 90% in cirrhotic liver
  • Asia + Africa highest (HBV)
  • Taiwan: historically high; HBV vaccination program reducing
  • MASLD/MASH-related rising globally

360.1.2 Risk Factors

  • HBV — top globally
  • HCV — declining with DAAs
  • ALD — alcohol
  • MASLD/MASH — rising
  • Aflatoxin — corn, peanuts contamination
  • Hemochromatosis
  • Wilson, alpha-1 AT, tyrosinemia
  • PBC, advanced AIH

360.1.3 Surveillance

  • Indications:
    • Cirrhosis (any cause)
    • HBV cirrhosis (more frequent if HBeAg+ or family history)
    • HBV non-cirrhotic high-risk (Asian male > 40, Asian female > 50, African > 20, family history)
  • Method: abdominal ultrasound ± AFP every 6 months
  • AFP alone not adequate

360.1.4 Diagnosis

360.1.4.1 LI-RADS (Liver Imaging Reporting and Data System)

  • LR-5 = definitively HCC
  • Based on multiphase CT or MRI features
  • Arterial enhancement + washout in portal venous/delayed phase + capsule appearance

360.1.4.2 When to Biopsy

  • Atypical imaging
  • Cirrhosis without typical features
  • Non-cirrhotic liver

360.1.5 Staging (BCLC)

Stage Description Treatment
0 (Very early) Single ≀ 2 cm, no portal HTN, PS 0 Ablation
A (Early) Single OR ≀ 3 nodules each ≀ 3 cm, preserved liver, PS 0 Resection, ablation, transplant
B (Intermediate) Multinodular, preserved liver, PS 0 TACE
C (Advanced) Portal invasion, EHD, PS 1-2 Systemic therapy
D (Terminal) End-stage liver, PS 3-4 Supportive

360.1.6 Treatment

360.1.6.1 Early Stage (BCLC 0, A)

Resection: - Single tumor + preserved liver + no portal HTN - Best for non-cirrhotic - Recurrence 50-70% at 5 years

Ablation (radiofrequency, microwave): - Small tumors (< 3 cm) - Alternative to resection for small early HCC - Comparable outcomes for ≀ 2 cm

Transplant: - Milan Criteria: single ≀ 5 cm OR ≀ 3 each ≀ 3 cm - 5-year survival 70%+ - Downstaging strategies

360.1.6.2 Intermediate Stage (BCLC B)

TACE (Transarterial Chemoembolization): - Conventional (cTACE) with lipiodol + doxorubicin - DEB-TACE (drug-eluting beads) - Multinodular without vascular invasion

TARE (Transarterial Radioembolization): - Y-90 microspheres - Alternative to TACE - Tumor + portal vein thrombosis

360.1.6.3 Advanced Stage (BCLC C)

Immunotherapy (First-Line): - Atezolizumab + bevacizumab (IMbrave150) — preferred - Durvalumab + tremelimumab (HIMALAYA, STRIDE) - Pembrolizumab + lenvatinib (LEAP-002 failed) - Tislelizumab (RATIONALE-301)

Targeted Therapy (First-Line if IO contraindicated): - Sorafenib (SHARP, original first-line) - Lenvatinib (REFLECT)

Second-Line: - Regorafenib (RESORCE — post-sorafenib) - Cabozantinib (CELESTIAL) - Ramucirumab (REACH-2 — AFP > 400) - Nivolumab (Checkmate-040 — post-sorafenib)

360.1.7 Prognosis

  • BCLC 0/A: 5-yr 50-70%
  • BCLC B (TACE): median 20-30 mo
  • BCLC C (systemic): median 12-19 mo (improving with IO)
  • BCLC D: weeks-months
360.1.7.0.1 Cholangiocarcinoma (CCA)

360.1.8 Anatomy

  • Intrahepatic (iCCA) — within liver
  • Perihilar (pCCA, Klatskin) — bifurcation/hilum
  • Distal (dCCA) — below cystic duct

360.1.9 Epidemiology

  • Rising incidence
  • iCCA increasing
  • Risk factors:
    • PSC (top in Western)
    • Hepatolithiasis
    • Liver flukes (Opisthorchis, Clonorchis — Asia)
    • Biliary cysts
    • HBV, HCV, MASLD
    • Asbestos, dioxin

360.1.10 Presentation

  • Jaundice (perihilar, distal)
  • RUQ pain
  • Weight loss
  • Sometimes incidental

360.1.11 Diagnosis

  • Imaging (CT, MRI, MRCP)
  • ERCP with brush cytology
  • Biopsy
  • CA 19-9 elevated
  • Molecular: FGFR2 fusion (10-15% iCCA), IDH1 mutation (15-20% iCCA), BRAF, HER2

360.1.12 Treatment

360.1.12.1 Resection

  • Only curative option
  • ~ 30% candidates
  • 5-yr 20-40%

360.1.12.2 Liver Transplant for Hilar CCA

  • Mayo Protocol: early hilar CCA + neoadjuvant chemoradiation
  • Strict selection
  • 5-yr survival ~ 65% (in protocol)

360.1.12.3 Adjuvant

  • Capecitabine (BILCAP trial)

360.1.12.4 Advanced/Metastatic

First-Line: - Cisplatin + gemcitabine (ABC-02, classic) - Cisplatin + gemcitabine + durvalumab (TOPAZ-1, 2022 — new SOC) - Cisplatin + gemcitabine + pembrolizumab (KEYNOTE-966)

Targeted (Second-Line): - Pemigatinib (FGFR2 fusion) FDA 2020 - Futibatinib (FGFR2) FDA 2022 - Infigratinib (FGFR2) - Ivosidenib (IDH1 mutation) FDA 2021 - Dabrafenib + trametinib (BRAF V600E) - Trastuzumab combinations (HER2) - Larotrectinib, entrectinib (NTRK fusion)

360.1.12.4.1 Gallbladder Cancer
  • Rare
  • Risk: gallstones (chronic inflammation), porcelain gallbladder, GB polyps > 1 cm, PSC
  • Often incidental at cholecystectomy
  • Treatment: resection (cholecystectomy + liver bed + lymph nodes for invasive); gem/cis for advanced
  • Poor prognosis
360.1.12.4.2 Ampullary Cancer
  • Pancreatobiliary or intestinal type
  • Whipple procedure
  • Better prognosis than pancreatic adenocarcinoma
360.1.12.4.3 Gastrointestinal Stromal Tumor (GIST)
  • KIT or PDGFRA mutations
  • Imatinib — TKI; revolutionized treatment
  • Sunitinib, regorafenib, ripretinib, avapritinib subsequent lines
  • Surveillance for mets
360.1.12.4.4 Neuroendocrine Tumors (NETs)
  • GI tract (carcinoid) + pancreas
  • Functional vs non-functional
  • Octreotide, lanreotide somatostatin analogs
  • Everolimus (RADIANT-4)
  • Sunitinib (pNET)
  • PRRT (177Lu-DOTATATE) — NETTER-1
  • Carcinoid syndrome: flushing, diarrhea, right heart valve disease (TIPS)

360.1.12.5 🩺 床邊速查

  • HCC surveillance: US ± AFP q6 mo for cirrhotic + HBV high-risk
  • HCC diagnosis: LI-RADS LR-5 — arterial enhancement + washout + capsule
  • BCLC staging integrates tumor + liver function + PS
  • HCC first-line systemic (advanced): atezolizumab + bevacizumab (IMbrave150)
  • CCA risk: PSC, hepatolithiasis, flukes
  • TOPAZ-1 (2022): durvalumab + cis/gem first-line CCA
  • Pemigatinib (FGFR2), ivosidenib (IDH1) targeted CCA
  • GIST: imatinib (KIT/PDGFRA)