Primary Liver Carcinoma

1. Primary Liver Carcinoma Chen Yingxuan Department of Gastroenterology,Renji Hospital Shanghai Institute of Digestive Diseases

2. Definition hepatocellular carcinoma (HCC)-- derived from hepatocytes cholangiocarcinoma (CC)-- arising from intrahepatic bile duct epithelium combined hepatocellular and cholangiocarcinoma (cHCC-CC)-- involving both hepatocellular and cholangiocellular components in the same tumor

3. Morphological classification lump lesions nodular lesions Diffused lesions

4. Distribution of HCC

5. Incidence(per 100,000 population) of HCC in China

6. Aetiology Hepatitis B virus Hepatitis C virus Liver cirrhosis Aflatoxins (AF) Others

7. Clinical Presentation

8. Symptoms-early stage No symptom/No specific symptoms Pain Poor appetite Early satiety Abdominal swelling Weight loss Weakness, tiredness An awareness of a lump in the upper abdomen Fever

9. Presentation with symptoms of advancing cirrhosis Pruritus Jaundice Variceal bleeding Cachexia Hepatic encephalopathy Increasing abdominal girth (portal vein occlusion by thrombus or tumor associated with rapid onset of ascites)

10. Physical Findings Hepatomegaly Jaundice Ascites Splenomegaly spider angiomata Pedal edema Periumbilical collateral veins Enlarged hemorrhoidal veins

11. hypoglycemia polycythemia hypercalcemia Paraneoplastic Manifestations

12. Complications Hepatic encephalopathy Gastrointestinal bleeding Cancer rupturing and bleeding into the abdominal cavity Infection

13. Diagnosis

14. Serum Tumor markers Alpha-fetoprotein (AFP) an a1-globulin normally present in high concentration in fetal serum but in only minute amounts thereafter Normal levels < 10 ng/ml Elevation:75% of HCC cases, active liver disease, embryonal cell carcinomas, metastatic cancer in the liver

15. Alpha-fetoprotein (AFP)-clinical significance AFP >400?g/L, up to 1 month or AFP>200 ?g/L , up to 2 months; and excluding patients with pregnant, active liver disease, embryonal cell carcinomas screening or primary diagnosis ( detection of HCC at an earlier stage, often before the development of symptoms) following the response to treatment Serum Tumor markers

16. Serum Tumor markers Fucosylated a-Fetoprotein Des-?-carboxy Prothrombin a-l-Fucosidase ?-GT-II

18. Imaging Studies-Ultrasonography

19. CT of large HCC

20. Inoperable extensive liver metastases

21. Imaging Studies-MRI

22. Imaging Studies- Angiography

23. Biopsy This biopsy may be obtained by a fine needle under local anesthesia, using ultrasound or CT scan to guide the needle into the tumor Lesions that are 2-3 cm or smaller may be dysplastic nodules in a cirrhotic background. These probably are premalignant, and obtaining a biopsy is especially important to distinguish them from HCC. Obtaining a biopsy may be unnecessary in patients who will undergo resection regardless of diagnosis, such as those without cirrhosis or evidence of metastatic disease.

24. Histologic Findings

26. Clinical diagnostic standard AFP >400?g/L, excluding patients with pregnant, active liver disease, embryonal cell carcinomas and hepatic metastases, accompanied by palpable hepatic mass or imagining scan of the liver to detect for the presence of tumor nodule(s) AFP <400?g/L, excluding patients with pregnant, active liver disease, embryonal cell carcinomas and hepatic metastases, as well as confirming the presence of the mass by using at least two imaging modalities or showing two positive serum markers and one imaging modality The presence of the clinical presentation and signs of distant spread, excluding hepatic metastases 2001 the 8th National Liver Cancer Conference

27. Differentials Cirrhosis Metastatic disease Benign tumor of the liver Liver abscess

28. Staging-TMN(Tumor, node, and metastases ) T1 Solitary tumor smaller than or equal to 2 cm No vascular invasion T2 Solitary tumor smaller than or equal to 2 cm, with vascular invasion Multiple tumors, in 1 lobe only, smaller than or equal to 2 cm, no vascular invasion Solitary tumor larger than 2 cm, no vascular invasion T3 Solitary tumor larger than 2 cm, with vascular invasion Multiple tumors, in 1 lobe only, with vascular invasion T4 Multiple tumors involving more than 1 lobe Involvement of a major branch of the portal or hepatic vein

29. Staging-TMN(Tumor, node, and metastases ) N0 - Indicates no nodal involvement N1 - Indicates regional nodal involvement M0 - Indicates no distant metastasis M1 - Indicates metastasis presence beyond the liver

30. Stage grouping Stage I = T1 + N0 + M0 Stage II = T2 + N0 + M0 Stage IIIA = T3 + N0 + M0 Stage IIIB = T1-3 + N1 + M0 Stage IVA = T4 + N0 + M0 Stage IVB = T1-4 + N0-1 + M1

31. Treatment

32. Treatment options Surgical resection and liver transplantation Transcatheter arterial chemoembolisation (TACE) Percutaneous Ethanol Injection Radiofrequency ablation Systemic treatment with chemotherapy Radiotherapy Others

33. Surgical The only proven potentially curative therapy for HCC hepatic resection liver transplantation The main prognostic factors for resectability tumor size and liver function Patients with single small HCC (<=5 cm) or up to three lesions (<=3 cm )

34. hepatic resection Tumor confined to one lobe of the liver and be favorably located The nontumorous liver tissue should not be cirrhotic Higher success rates in tumors smaller than 2 cm with no vascular invasion (T1 N0 M0, stage I) Resection is feasible in only about 15% of patients A 5-year survival rate : 40%

35. Liver transplantation should be considered in any patient with cirrhosis and a small (5 cm or less single nodule or up to three lesions of 3 cm or less) HCC the prognosis for long-term survival is poor (20-30%) limited availability of organs and long wait times

36. producing tumor necrosis Indications palliation of inoperable primary or secondary hepatic malignancies and reduction of pain Preoperation: to reduce tumor mass Postoperation:to influence tumor rests or recurrences Contraindications more than 75% of the liver is involved by tumor presence of insufficiency of the liver, significant portal hypertension, occlusion of the portal vein or hepatorenal syndrome TACE

37. Antineoplastic scheme FAP: 5-FU 750~1000 mg MMC 10~20 mg CDDP 60~80 mg FMP: 5-FU 750~1000 mg ADR 20~40 mg CDDP 60~80 mg

38. Before TACE

39. First TACE: HCC prior being submitted to transcatheter arterial chemoembolization. The angiographic study allows clear visualization of the hypervascular tumor

40. After second TACE: which is further studied by means of superselective catheterization

42. PEI has been shown to produce necrosis of small HCC. It is best suited to peripheral lesions, less than 3 cm in diameter Percutaneous Ethanol Injection

43. Radiofrequency Ablation(RA) using a probe placed into the tumor mass A single probe can destroy lesions of up to 3 cm and a multiple tipped probe has been used to target lesions of up to 6 cm in diameter

44. Systemic chemotherapy a poor response - caused by the universal expression of the multidrug resistance gene protein on the surface of the malignant cells The most active drugs - doxorubicin, cisplatin, and fluorouracil Response rates - under 10% Combination chemotherapy does not add any benefit to single-agent chemotherapy

45. Radiatherapy

46. Other Treatment Methods High Intensity Focused Ultrasound (HIFU) Chinese medicine

47. Prognosis Overall prognosis for survival depends on the extent of cirrhosis and tumor stage curative resection - a median survival of 4 years not to be treated - a median survival of 3 months