1. Liver cancer is a major health problem in China, being the fourth most common cause of cancer death, with high rates in Eastern and Southeastern China. 2. The main risk factors for liver cancer are chronic hepatitis B and C infections, along with aflatoxin exposure and heavy alcohol use. 3. Treatment options for liver cancer include surgical resection, liver transplantation, and percutaneous ablation techniques like radiofrequency ablation for early stage disease. Transcathelial arterial chemoembolization is often used for unresectable tumors.

1. Department of Hepatobiliary Oncology,SYSUCC Anti-liver cancer team Shengping Li, M.D., Ph.D

2. Advanced stage Low resection rate High recurrence Decompensation liver function Poor prognosis Fierce “癌王” “lion king”

3. Liver cancer PLC (Primary Liver Cacner) Secondary Liver Cancer HCC(Hepatocellular carcinoma) CCC(Cholangiocellular carcinoma) HCC and CCC mixed HCC

4. Epidemiology “ Hot spots” – 150 per 100 000 US, Australia : 2 per 100 000 The fifth most common cancer worldwide CA Cancer J Clin 2005

5. High incidence In China Shanghai Jiangsu Fujiang Guangdong Guangxi Epidemiology

6. Trend of Death rate of malignant tumor in China Lung Liver Stomach 128 2004-2005 Stomach Liver Lung 106 1990-1992 Stomach Esophagus Liver 80 1973-1974 Three leading causes of Ca. death Death Rate (per100,000) Period(years)

7. Etiology Hepatitis Alcoholism Environmental factors molecular and Cytogenetic alterations

8. HBV 80% (Asia and Africa), 100 million china HCV 70% (Japan,West countries) Hepatitis virus infection

9. Alcoholism: alcoholic cirrhosis

10. Food contaminated with aflatoxin Decayed peanut,corn Turkey Liver cancer

11. Liver Flukes (Clonorchis sinensis )

12. Liver Flukes Infestation

13. Mutation of oncogene and tumor suppressor gene （癌基因和抑癌基因的突变） N-ras,c-myc,cfms,CSF-1R, IGF-II ， p53 ， TTR, DLC-1, LPTS, WFDC1, HCCS1, HCRP1, 17HSDB2 Chromosomal alterations ( 染色体改变） Gain （获得） :1q,8q and 20q Lose （缺失） : 4q,8p,13q,16q, and 17p ( Li SP, et al . J Hepatology 2001) Molecular and cytogenetic aberration （分子和细胞遗传学变异）

14. Peoples lived in high incidence of liver cancer area Peoples persistent infection of hepatitis virus Family history of liver cancer Liver cancer history previously High Risk Group

15. Early stage Subclinical stage Non symptom and sign Clinical manifestation

16. Abdominal pain and distention Weight loss Hepatomegaly ： 80% Abdominal mass Jaundice ,ascites Clinical stage

17. Diagnosis of HCC Serological (tumor markers) Radiological Cytological Histological Either alone or in combination

18. Tumor markers for HCC Most common used

19. Diagnostic Imaging for HCC

20. Radiology--US Ultrasound Availability, cost Operator dependant Therapeutic role.

21. Radiology--CT Triphasic CT detect 30 – 40% more tumour nodules than conventional CT. Lipiodol Retained by all hypervascular liver tumours.

22. Radiology--MRI Slightly higher sensitivity than CT in detecting hepatic lesions. Cost, availability.

23. Diagnosis and treatment simultaneously Invasive, not routinely used Radiology--angiograph

24. Expensive Whole body scaning Tumor cell Function Radiology-- Positron Emission computed Tomography, PET/CT

25. Liver Biopsy Biopsy now rarely required to diagnose HCC. Avoid biopsy of potentially resectable tumour. Risk of needle track seeding 1 – 3% Risk of bleeding

26. US and CT most commonly used clinically Diagnostic imaging for HCC

27. AFP≥400 n g/L, palpable mass or space-occupying lesions in the liver by imaging 2. AFP<400 n g/ L, specific liver cancer images confirmed by at least two kinds of imaging scanning 3. Clinical manifestation of liver cancer with pathological diagnosed extrahepatic liver cancer and metastases liver tumor ruled out Standard rule for Diagnosis of HCC

28. Clinical Application of AFP 1.Screening of liver cancer 2.Dianosis of liver cancer 3.Predicting prognosis after treatment 4.Surveillance of recurrence after treatment( decrease to normal level within 1-2 months after resection)

29. Differential diagnosis AFP positive chronic active hepatitis, cirrhosis, testicular tumor, pregnancy AFP negative haemangioma, metastatic liver carcinoma, abscess, focal nodular hyperplasia (FNH), hepatic hydatidosis

30. Pregnancy with HCC Delivery baby and resection of HCC simultaneously

31. Hepatic haemangioma

32. Colon cancer liver metastasis

33. Focal Nodular Hyperplasia (FNH)

34. Hepatic Abscess

35. Hepatic Hydatidosis

37. Therapeutic Option for HCC

38. Surgery Langenbuch 1888 first left hepatic lobectomy Tiffany 1890 first liver resection for solid tumour Starzl 1963 first liver graft

39. Principles of Surgical Management Determining resectability  Stage of tumour  Functional hepatic reserve 80%-90% of HCC occur in cirrhotic livers Less than 20% of patients with HCC are candidates for resection at time of presentation.

40. 1. Staging TNM Stage III, IV unresectable Okuda CLIP (Cancer of the Liver Italian Program) Barcelona Staging Classification Performance scores, Okuda, tumour morphology French Staging Classification Performance scores, LFT, US

41. TNM Staging System

42. staging Because the combined impact of liver disease and tumor burden is not yet fully understood, and the cause of HCC may vary geographically, none of the currently used staging systems fulfils all the requirements for stratification of patients with HCC into groups of different prognosis and therapeutic recommendations. None of the staging systems is universally accepted.

43. 2. Functional Reserve Resection only of benefit in patients with adequate functional reserve. Assessment of liver function : Synthetic capacity of liver Serum albumin, prothormbin time Excretion of metabolites Indocyanine dye test, bilirubin, bile acid profile Child-Pugh Classification

44. Child Pugh Classification

45. 2. Functional Reserve Portal hypertension Estimation of likely remaining liver volume after resection Comorbidities ASA / Performance scores Nutritional state : Perioperative nutritional support decreases post operative morbidity

46. 5-year survival 26-50%, mean 30% 5 years recurrence rate is about 70% A critical clinical problem Hepatectomy

47. 6 m Pre-op

48. Cutting edge recurrence

49. Liver transplantation Potentially resect HCC while replacing the cirrhotic liver Milan criteria for HCC Single lesion <5cm or upto three lesions <3cm

50. Limitation Immunosuppression Recurrent hepatitis Recurrent HCC Shortage of donors Consider “bridging therapy” to prevent tumour progression. Living donors

51. Non Surgical Management Transcatheter Arterial Chemoembolization Percutaneous microwave coagulation therapy Percutaneous ethanol injection Radiofrequency Ablation Cryosurgery Systemic Chemotherapy Hormonal therapy Immunotherapy Gene Therapy Chinese medicine

52. Percutanous intervention PEI: percutanous ethanol injection RF: Radiofrequency ablation MCT: microwave coagulation thermotherapy LT: Laser thermotherapy Cryoablation Best option for small unresectable HCC

53. 将 10 枚象“弹头”一样的小电极通过穿刺针管送入癌组织，多枚小电极从不同的角度和方向“锁定”癌症组织区域，由计算机测算出射频治疗所需的最佳温度，时间，功率和阻抗，由小电极发出高能射频波，在 100—120℃ 的高温下，使癌组织蛋白发生凝固性坏死，达到杀灭癌组织的效果。 3.5cm/15G 10 electrodes Lee Veen needle

54. Radiafrequency ablation,RF Alternative to PEI Applied percutaneously,laparoscopically, during laparotomy Expensive but offer a better local control Ablation of tumor large than 5 cm in diameter

56. The most widely used treatments for HCCs which are unresectable or cannot be effectively treated with percutaneous interventions. Embolization agents: Lipiodol,gelfoam Chemotherapeutics: doxorubicin, 5-Fu, mitomycin, cisplatin Partial responses in 15-55% of patients Delays tumor progression and vascular invasion Prolongs the survival time compared to conservative management. TACE or TAE

57. TACE or TAE Patients liver function Child A Without vascular invasion or extrahepatic spread. Advanced liver disease (Child B or C), treatment-induced liver failure may offset the antitumor effect or survival benefit of the intervention. Postoperative adjuvant TACE may improve survival in patients with risk factors for residual tumor

58. Tumor shrinkage post-TACE

59. Principles of management Treatment in early stage Combination therapy Actively( time and again)

60. Metastasis of HCC Intrahepatic ---port vein pathway, satellite Extrahepatic: lung Lymphatic pathway: CCC Invasion periheaptic organs directly Abdominal implantation: tumor rupture

61. HCC metastasis

62. Continuing challenges Prevalance of chronic hepatitis Low resection rate High recurrence rate post-resection Shortage of liver donor Optimal combination therapy Molecular staging system

63. Thank you!