1. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer 

2. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer 

3. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer Primary Liver Cancer Secondary Liver Cancer  Hepatic neuroendocrine metastasis

4. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer Primary Liver Cancer Secondary Liver Cancer  Hepatic neuroendocrine metastasis

5. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer Incidence and mortality Worldwide primary liver cancer is considered the fifth most significant cancer in terms of number of cases (437,000 or 5.4% of new cancer cases) It is the fourth most significant in terms of mortality (427,000 deaths or 8.2% of the total) The small difference in incidence and mortality reflects the extremely poor prognosis of primary liver cancer D.Parkin et al, CA Cancer J.Clin 1999: 49(1) 33-64 

6. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer hepatocellular carcinoma (HCC) cholangiocarcinoma haemangioendothelioma haemangioblastoma angiosarcoma primary sarcoma HCC is the most common primary malignancy of the liver (85%) Types of primary liver cancer: 

7. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer  hepatitis virus infections (HBV, HCV)  drugs (mostly alcohol and tobacco)  mycotoxins or phytotoxins  liver diseases  metabolic diseases  chemical agents and inorganic substances  medication  ionizing radiation HCC - Risk factors: 

8. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer pain in the upper abdomen bloating, flatulence anorexia, nausea weight loss fatigue, weakness stool irregularities HCC - Symptoms: HCC develops without subjective complaints and is therefore usually detected (too) late! Complains - if any - are very varied: 

9. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer fever subicterus ascites latent encephalopathy arterial murmur tenderness upon pressure palpable tumour perihepatic friction HCC - Clinical findings: 

10. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer laboratory findings (incl. alpha-fetoprotein=AFP) sonography computer tomography percutaneous fine-needle biopsy (FNB) laparoscopy HCC - Diagnosis: 

11. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer HCC - Diagnosis – Computer Tomography (CT): 

12. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer HCC - Diagnosis - Laparoscopy: 

13. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer HCC - Prognosis: The prognosis is determined by the tumour mass and its speed of growth at the time of diagnosis. Signs of poor prognosis are:  considerable size of tumour (>5cm)  infiltrative growth  multilocular growth  metastatic spread 

14. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer HCC - Prognosis: The natural course of disease shows an average survival rate of 5 months (2-8 months). Some 3% of patients survive for 5 years 

15. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer TNM staging of primary liver cancer: T 0 Disease free T 1 <2cm, no vascular invasion T 2 <2cm, vascular invasion or: >2cm, no vascular invasion T 3 >2cm with vascular invasion or: multiple lesions T 4 multiple lobes, macrovascular invasion N 0 no regional lymph node involvement N 1 regional lymph node involvement M 0 no metastasis M 1 metastasis 

16. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer HCC – Staging: 0 points1 point Liver invasion<= 50%> 50% Ascitesnoyes Bilirubin<= 3mg/dl> 3mg/dl Albumin> 3g/dl<= 3g/dl stage 1: 0 points, stage 2: 1-2 points, stage 3: 3-4 points K.Okuda et al., 1993 

17. Training Module 5 – Version 1.1 For Internal Use Only ® Primary Liver Cancer HCC - Complications:  acute liver failure  portal hypertension The cause of death is anorexia with tumour cachexia, accompanied by signs of circulatory and renal failure. Occasionally there is intraperitoneal hemorrhage and a tumour rupture with formation of hemorrhagic ascites 

18. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer Primary Liver Cancer Secondary Liver Cancer  Hepatic neuroendocrine metastasis

19. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer Many Patients with cancer will develop hepatic metastases Liver metastases develops via the portal vein, via the hepatic artery or via lymphatic permeation. In many cases there will be widespread dissemination and liver involvement will not be a separate medical problem 

20. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer If the metastases are widespread the expectation of life is only 2-3 months Metastatic carcinoid tumours may be very slow growing, and in this disease hepatic metastases are compatible with survival of 3-5 years 

21. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer Blood circulation 

22. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer Most common ‘feeding’ primary tumours breast lung melanoma colorectal Only portal hepatic metastases have a low probability of extrahepatic disease 

23. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer Hepatic colorectal metastasis Approximately 160,000 new cases of colorectal cancer (CRC) are diagnosed each year in the United States Approximately 62,000 deaths are expected due to colorectal cancer (CRC) in 2006 (US) 

24. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer 50% of patients in whom the primary tumour drains into the portal vein will develop hepatic metastases! 50 Hepatic colorectal metastasis 

25. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer cancer umbilicus metastases 

26. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer 

27. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer Number of nodes / lobes affected A solitary node is found in some 10% of patients at the time of diagnosis In 15-20% of cases only one lobe is effected At the time of diagnosis most patients have multiple nodes in both lobes 

28. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer increasing malaise feeling of weakness febrile attacks upper abdominal pain anorexia weight loss Symptoms: But: Metastases are characteristically asymptomatic. 

29. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer hepatomegaly (liver growth) hardening of the liver occasional palpability of tumour nodes occasional ascites occasional thrombosis of the portal vein occasional swelling of the lymph nodes Clinical findings: 

30. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer biochemistry: rise in γ-GT is characteristic tumour markers sonography computer tomography (CT) MRI explorative laparoscopy fine needle biopsy (FNB) Diagnosis: 

31. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer Laboratory findings: 

32. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer Prognosis (CRC-Metastasis): The natural course of disease shows an average survival rate of 3-10 months The 5-year survival rate is 2% to 8%  In almost all cases the patients die because of their metastatic liver disease

33. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer Primary Liver Cancer Secondary Liver Cancer Hepatic neuroendocrine metastasis 

34. Training Module 5 – Version 1.1 For Internal Use Only ® Secondary Liver Cancer Hepatic neuroendocrine metastasis: Neuroendocrine tumours (NET) are rare tumours arising from cells within the gastrointestinal mucosa and pancreatic islet that normally secret regulatory hormones Up to 93% of patients with neuroendocrine tumours develop liver metastasis. A mean survival up to 8.1 years has been reported 

35. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer Primary Liver Cancer Secondary Liver Cancer Hepatic neuroendocrine metastasis 

36. Training Module 5 – Version 1.1 For Internal Use Only ® Liver Cancer What is most important to remember? HCC – Incidence and Prognosis CRC – Liver Metastasis NET 

37. Training Module 5 – Version 1.1 For Internal Use Only ® Further Readings DeVita et al.: Cancer – Principles & Practice of Oncology 2005 E.Kuntz & H.-D.Kuntz: Hepatology 2002 S.T.Rosen: Liver-Directed Therapy for Primary and Metastatic Liver Tumors 2001 T.R.Harrison et al.: Principles of Internal Medicine 1994 Liver Cancer