1. HEPATOCELLULAR CARCINOMA Monton

2. HCC in Thailand Most common cancer in Thai male Incidence 5 x 100,000 / year Male : female = 3-8:1 Age > 40 yr

3. HCC in Thailand 60-90% associated with cirrhosis Risk factor – HBV35-85% – HCV 18.6% – Alcohol ~10% – etc. aflatoxin

4. Multisteps carcinogenesis INITIATION PHASE PROMOTION PHASE CIRRHOSIS HBV HBC AFLATOXIN ALCOHOL

5. Cause of death Hepatic failure39-45% GI bleeding13.8-23.3% Cancer death10%

6. Diagnostic criteria EASL conference 2000 Cyto-histological criteria Non-invasive criteria(cirrhosis) 1.Radiological criteria : 2 imaging - focal mass > 2 cm - 1 imaging show hypervascularization 2.Combined criteria - 1 imaging mass >2cm,hypervascularization - AFP > 400 ng/ml

7. Staging No standard staging system Most system focus on 1.performance status 2.tumor characteristics intrahepatic and extrahepatic 3.liver function French,CLIP,BCLC,CUPI,TNM

8. Treatment Curative –Surgery –Liver transplantation –Percutaneous : PEI,RFA Palliative –TACE –Hormone –Systemic chemotherapy

9. Surgery First choice in non-cirrhotic pt 5yr survival ~ 50% High recurrent rate : 50% in 3yr Suspect undetected micrometastasis 4,000-10,000 baht

10. Liver transplantation Cure underlying cirrhosis 5yr survival ~ 70% Milan criteria 1 mass, < 5 cm 3 mass, < 3 cm Less available Long term immunosuppression 300,000 – 500,000 Baht

11. Percutaneous Alternative in unresectable tumor No destruction to non-tumor tissue Can do in cirrhosis Tumor seeding is problem PEI : percutaneous ethanol injection –2,000 baht RFA : radiofrequency ablation –40,000 baht

12. TACE Transarterial chemoembolization Palliative treatment Principle –Cytotoxic agent(doxorubicin/cis) + lipiodol –Embolization Improvement in 2yr survival 10,000 – 30,000 baht

13. Contraindication of TACE Decompensated cirrhosis particularly bilirubin > 2 mg/dl Encephalopathy Reverse or absent portal flow Tumor burden > 50% of liver Renal failure Active infection

14. Systemic therapy Hormonal rx – not improve survival Systemic chemotherapy –not improve survival compared with best supportive care

15. Future trends Antiangiogenic agent –Vascular endothelial growth factor inhibitor Immunotherapy –Tumor specific effector T-cell Gene therapy – Intratumoral immunomodulatory cytokine

16. Problem Most patients are unresectable High recurrent rate after surgery Cannot detect micrometastasis Early detection of HCC is appropriate

17. HCC surveilance Focus on cirrhotic patients Tumor doubling time ~ 6 mo Tools are 1. AFP 2. Ultrasonography

18. AFP Produced from – Fetal liver cell – Yolk sac Normal range 10-20 ng/ml AFP increases in –exacerbation of chronic viral hepatitis (20-250 ng/ml) –Germ cell tumor

19. AFP cut-off Cut-off sens spec NPV PPV 20 60 89.4 97.7 25.1 200 22.4 99.4 400 17.1 99.4 Trevisani et al,J Hepatol,2001

20. USG Sensitivity USG 79.4 CT87.6 MRI88.9 Yao et al,J Hepatol,2001

21. Surviellance & recall strategy USG/AFP q 6mo liver nodule no nodule 1-2cm >2cm <1cm AFP^ AFP- FNAB AFP>400 USG/3mo spiralCT imaging no HCC HCC surveillance/6mo Bruix J et al. J Hepatol,2001

22. Thank you