1. Eun Sun Jang, M.D., Ph.D Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine Diseases in the Liver - Hepatocellular carcinoma-

2. Anatomy of Liver Liver Gallbladder Large bowel (Colon) Small bowel Stomach Esophagus Rectum

3. Anatomy of Liver Right lobe Left lobe Gall bladder The largest organ Weight: 1,200~1,500 g

4.  Metabolism 1) Nutrients: carbohydrate/glucose, protein/amino acid, lipid 2) Bilirubin: bilirubin, bile acid 3) Ammonia 4) Hormone, vitamin  Protein synthesis - Albumin, lipoprotein, bile acid, coagulating factors  Detoxification : Drug, hormone, alcohol  Immune function by Kupffer cell Functions of Liver

5.  Life-threatening diseases 1) Hepatitis (liver inflammation) - Viral (HAV, HBV, HCV), autoimmune, toxic, drug-induced, metabolic 2) Liver cirrhosis 3) Cancer: hepatocellular carcinoma (HCC), cholangiocarcinoma  Benign diseases 1) Fatty liver: alcoholic, non-alcoholic 2) Cholestatic (accumulation of bile) liver disease 3) Benign tumors: hemangioma, cyst Liver Diseases

6. Hepatic failure Hepatic failure Acute hepatitis Acute hepatitis Chronic hepatitis Chronic hepatitis Liver cirrhosis Liver cancer Course of liver disease

7. The incidence of HCC The World Health Organization GLOBOCAN 2002

8. Cancer-related deaths in Korea 2009, National Cancer Information Center 3.4/100 men/year1.4/100 women/year

9. Primary Liver Cancer Hepatocellular carcinoma (HCC) : > 80% Derived from hepatocytes Cholangiocarcinoma (CC) : about 15% Derived from biliary epithelial cells Combined HCC-CC : 1.0% – 14.3%

10. 정상 간

12. The main risk factors for HCC Hepatitis B Hepatitis C Alcoholism Cirrhosis of the liver Non-alcoholic steatohepatitis Type 2 diabetes (probably aided by obesity) Aflatoxin Iron and copper deposition SNUBH

13. Cirrhosis is a major risk factor of HCC Chronic hepatitis LC HCC LC in chronic hepatitis pts 10-20% / 5 yr HCC in LC pts : 1-5% / yr HBV >> HCV, hepatic adenoma, hereditary tyrosinemia Noncirrhotic Pathway

14. Diagnosis of Hepatocellular carcinoma 2010, AASLD Practice Guideline Based on Non- invasive diagnosis

15. Blood Flow though Liver Portal vein (70%) Hepatic artery (30%) Hepatic vein Inferior vena cava

16. Diagram of the mechanism underlying changes in drainage vessels (top) and histologic features (bottom) of HCC during multistep hepatocarcinogenesis Kitao A et al. Radiology 2009;252:605-614

17. Characteristics of HCC Hypervascularity & Washout

18. Treatment of HCC Curative treatment –Surgical resection –Liver transplantation –Percutaneous ablation: PEI & RFA Non-Curative treatment –TACE (Transarterial Chemoembolization) –Systemic chemotherapy –RT etc…. –Sorafenib : multikinase inhibitor

19. HCC Recurrence rate after resection 5Yr Survival rate: 50-70% 5Yr Recurrence rate: 60-80% H. Imamura et al. Journal of Hepatology 2003;38:200-207

20. Bimodal recurrence after HCC resection H. Imamura et al. Journal of Hepatology 2003;38:200-207

21. Early recurrence; intrahepatic metastasis Late recurrence; de novo carcinogenesis New lesion Intrahepatic microscopic metastatic foci

22. Sites of Extrahepatic HCC SiteNo of Pt. (N=148)No of Pt. with Other metastatic sites at initial Presentation Lungs81 (55%)23 / 81 (28%) Lymph Nodes 78 (53%)56 / 78 (72%) Bone41 (28%)27 / 41 (66%) Adrenal16 (11%)7 / 16 (44%) Peritoneum +/- omentum 16 (11%)9 / 16 (56%) Brain3 (2%)3 / 3 (100%) Rectum2 (1%)0 / 2 (0%) Spleen2 (1%)1 / 2 (50%) Diaphragm2 (1%)2 / 2 (100%) Duodenum1 (1%)1 / 1 (100%) Esophagus1 (1%)1 / 1 (100%) Pancreas1 (1%)1 / 1 (100%) Seminal vesicle1 (1%)1 / 1 (100%) Bladder1 (1%)1 / 1 (100%) Katyal S et al. Radiology 2000;216:698-703

23. HCC metastases to the lungs Katyal S et al. Radiology 2000;216:698-703

24. HCC metastases to the lymph node Katyal S et al. Radiology 2000;216:698-703

25. HCC metastases to the bone Katyal S et al. Radiology 2000;216:698-703

26. HCC metastases to the adrenal gl. Katyal S et al. Radiology 2000;216:698-703

27. HCC metastases to the peritoneum Katyal S et al. Radiology 2000;216:698-703

28. HCC Metastasis J Cancer Res Clin Oncol (2004) 130: 497–513

29. Mechanism of Sorafenib Cancer Research 2004;64:7099-7109

30. SHARP trial Llovet JM et al., Sorafenib in Advanced HCC NEJM 2008;359:378-90 Median Survival : 10.7 vs 7.9 months Asia-Pacific trial Cheng AL et al., Asia-Pacific trial Lancet Oncol 2009;10:25-34 Median Survival : 6.5 vs 4.2 months Sorafenib in Advanced HCC

31. Take Home Messages Most hepatocellular carcinoma arise in the setting of chronic liver disease. HCC is usually diagnosed with non-invasive imaging modalities because of its hypervascularity & washout. Intrahepatic recurrence after HCC resection shows bimodal peak (regional/remote). Effective systemic therapies should be developed in the future.