1 / 49

Malignant Tumors of the Liver

Malignant Tumors of the Liver. Hepatocellular Carcinoma (HCC) Dr. Izhar Levy Liver Unit/Hadassah Ein-Kerem. Primary Malignant Tumors of the Liver. Hepatocellulr Origin Hepatocellular carcinoma (HCC) Common cause of death in cirrhotic patients Bile duct origin Cholangiocarcinoma

ian-reeves
Download Presentation

Malignant Tumors of the Liver

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Malignant Tumors of the Liver Hepatocellular Carcinoma (HCC) Dr. Izhar Levy Liver Unit/Hadassah Ein-Kerem

  2. Primary Malignant Tumors of the Liver Hepatocellulr Origin Hepatocellular carcinoma (HCC) Common cause of death in cirrhotic patients Bile duct origin Cholangiocarcinoma Mesenchymal origin Hemangiosarcoma

  3. HCC - Pathogenesis • HCC develop in cirrhotic liver • (>90% of cases) rarely within normal liver • Pathogenesis: Multifactorial • Fibrosis/Ischemia/Chronic inflammation Mature HepatocyteTelomerase shortening Ischemia Oxidative stress Proliferative cytokines New clones neu – vascularization HCC DNA damage Similar scenario?

  4. Hepatic Nodules

  5. HCC - Epidemiology HCC is the most common malignancy in East Asia and Sub-Saharan Africa and the 5th common malignancy worldwide- 600,000/y The incidence of HCC in different countries correlate with the geographic distribution of chronic liver disease mainly - viral hepatitis China - Shanghai 60/105/y , Israel 3/105/y

  6. HCC- Epidemiology HCC incidence in cirrhotic patients 2% /year. Colombo M et al, NEJM 1991 325, 675-680 BRCA positive 1%/y Lung cancer – heavy smoker >age 50 1%/y 200 new HCC cases/year in Israel, most of them with pre-existing liver cirrhosis

  7. HCC- Prognostic factors Most HCC patients has also liver cirrhosis Two diseases in one person: Liver Cirrhosis and Liver Tumor • Prognostic liver factors • Child-Pugh score: • Albumin , Bili, INR Ascites , Encephalopathy • MELD: Bili, INR, Creat • Prognostic tumor factors: • Tumor number • Tumor size • AFP • Vascular invasion • (portal vein thrombosis)

  8. HCC- Natural history - prognosis Advance and symptomatic tumor -poor prognosis Median survival : several weeks to 3 months Wolf D & Shouval D 1984 Asymptomatic HCC Child – Pugh A Without treatment- : 3 year survival – 102 patients - no treatment - 50% Llovet et al Hepatology 1999:1:62-67 2 year survival – 25 patients- no treatment - 50 % Cotton et al. Gastroenterology 1989:96:1566-71

  9. HCC screening & surveillance • Case for screening & surveillance • 1- Very high incidence in the target population – Liver Cirrhosis • 2- Poor prognosis in Advance stage • 3- Curative treatments in early disease • 4- Low cost for screening & survaillance

  10. HCC - Screening • Goal of screening: • Early diagnosis of small tumor– Curative treatment • Early diagnosis: • Transplantation • Resection or RFA 5 year survival 50-60 % • Late diagnosis • Clinical symptoms 2 year survival 0% } Early diagnosis 10 year survival 50-70%

  11. HCC - Screening Screening for HCC is recommended in cirrhotic patients US of the liver is the screening tool. It is performed every 6 months in cirrhotic patients

  12. HCC- Screening Alpha-Feto-Protein (AFP) rise in: Pregnancy , Embryonic tumors (testis) , Cirhhosis (10-20%) and HCC Early HCC (20-30%) Advance HCC (70-80%) AFP is used combined with US. .

  13. HCC- Diagnosis Tumor biopsy is unnecessary in 70-80% of cases HCC within the normal liver – without liver disease tumor biopsy is necessary (<10% of the cases) HCC within the cirrhotic liver (>90% of the cases) : Hypervascular tumor Elevated AFP Different appearance from benign tumors and MET’s

  14. HCC - Hypervascular lesion with in cirrotic liver Angiography Tri-phasic CT

  15. Hypervascular lesion - HCC Non contract CT Contract CT

  16. HCC- Diagnosis HCC within: cirrhosis /advance fibrosis clinical –radiological diagnosis Liver mass AFP>400ng/ml Biopsy unnecessary Live mass , Typical Hyper vascular , cirrhotic liver AFP - normal Biopsy unnecessary Liver mass – Atypical hypo-vascular AFP- normal Biopsy necessary

  17. HCC- Diagnosis • HCC in cirrhosis /advance fibrosis • clinical –radiological diagnosis • Different appearance from benign tumors and MET’s Accuracy of clinical/radiological diagnosis is 95-97% Equal or better then pathological diagnosis Minimize the risk of tumor biopsy – bleeding & tumor seeding

  18. HCC- clinical manifestation Asymptomatic in early HCC RUQ pain: most common and non specific symptom Systemic manifestations: weakness, weight loss, fever, ascites Systemic symptoms are poor prognostic signs

  19. HCC- Treatment Systemic chemotherapy – no benefit Most patient are cirrhotic Hepatic decompensation , Infections, etc’ More than 40 RCT in the last 30 years failed to show any benefit of systemic chemotherapy

  20. HCC- Treatment • Liver Resection - not option 90% of patients: • nonresectable • inoperable • Systemic Chemotherapy • Not effective , limited due to cirrhosis • There were no treatment for HCC until mid 1980’s • Median survival was 3 months

  21. HCC- Treatment Since early 1990’s US Screening programs Mid 1990’s Dynamic imaging: CT (later on MRI) • Early diagnosis • Small and single tumors Curative and palliative Tx for HCC

  22. HCC- Treatment Tumor resection - treatment of choice Liver Cirrhosis and liver Tumor Most patients (90%) has either : non-resectable tumor or advance cirrhosis - inoperable patients

  23. Tumor resection 6 Month post resection

  24. מה דעתכם על ניתוח ?

  25. HCC-Treatment Loco-regional treatments: “Killing methods”: Alcohol ablation - 90% cure - single lesion <2cm Radiofrequency ablation - 90% cure- lesion <4cm TACE: Transe Arterial Chemo Embolaization

  26. 60 year old man – HBV + HCC

  27. One year post Alcohol ablation

  28. RFA -74Y, M ( HCV-HCC) T T Wide Necrosis

  29. HCC - treatments • Loco-regional treatments • TACE : Trans Arterial Chemo Embolization • Improve survival (Llovet et al, lancet 2002, 359 :1734-9) • Choice for non resctable and not eligible for Alcohol /RFA • Arterial catheterization - Targeted chemotherapy • Embolization of tumoral artery (temporary)

  30. Male age 78 HCV AFP 3 90 490

  31. 6 weeks post TACE AFP 490 6

  32. Male age 84 HCC Chemoembolization AFP>2500 Pre Tx תמונה Post Tx AFP-70

  33. HCC- Treatment RFA - Treatment of choice for Single HCC < 5 Cm’ Cure rate of single tumor ≤2cm’ 216 Pt’ - 97% Livraghi T et al Hepatology. 2008 Jan;47(1):82-9. TACE - Treatment of choice for Mmultifocal and large HCC TACE and RFA – Combined treatment - common practice

  34. RFA + Chemoembolization 61y ♀ HBV+HCC 1 3 2

  35. HCC- Recurrence The cirrhotic liver, once develops an HCC focus, is the fertile ground for the next HCC focus. 15-20% risk of new HCC/Year HCC recurrence rate after resection or RFA : 70-80% in 5 years >90% in 7 years

  36. HCC- Recurrence • Liver resection • recurrence in cirrhotic patients • 15 - 20% / year • 5 year- disease free survival for small HCC • <10-15% • Liver Transplantation (OLT or LRLT) • 5 year – disease free survival for small HCC • 60-70%

  37. HCC – Liver Transplantation Orthotopic Liver transplantation (OLT) is currently the only treatment that offer cure for both liver cirrhosis and HCC OLT is not performed Large and multifocal tumor- recurrence rate > 50% Age >67 due to organ shortage and old age 10% - are eligible for OLT

  38. HCC- Liver Transplantation • International criteria for liver transplantation • “Milan criteria” * • Single tumor <5cm or 3 nodules <3 cm’ • 5 year disease free survival (DFS) 70%. • Recurrence rate 5-10% at 5 years * N Engl J Med. 1996 Mar 14;334(11):693-9.

  39. 57 HCC patients transplanted in Hadassah between 1/2001 -9/2013 5 Year Survival 65%

  40. HCC- Liver Transplantation limitations: lack of organs Cost Only small tumors are candidate for OLT , advanced tumors has very high recurrence rate and are not eligible for OLT.

  41. HCC - Treatment • Liver transplantation ~ 5-10% • Liver resection ~ 5-10% • Loco-regional treatments ~ 30-40% • No treatment - 50% of patients • Multifocal or diffuse tumor , • Vascular invasion, metastasis • Advance cirrhosis • Sorafenib - Nexavar

  42. Treatment of advance HCCMolecular target therapy • Sorafenib : TK and multikinase inhibitor and anti-angiogenic, and Raf kinase inhibitory activity • Improve survival in advance HCC • Prolonged median survival from 7 to 10 months • Approved for child-A advance HCC patients who are not eligible for any other therapy. • N Engl J Med. 2008 Jul 24;359(4):378-90. • Cautious with side effects: weakness , diarrhea, rash

  43. HCC - Summary HCC incidence in cirrhotic patients 2-3% /y Screening and early diagnosis is mandatory for early diagnosis and curative treatments Diagnosis – Biopsy unnecessary in 70-80% of cases Prognostic Factors : Liver and tumor factors Liver resection - Early Child A cirrhosis High recurrence rate Large tumor not eligible for OLT

  44. HCC - Summary • Loco-regional therapy is very effective in small tumors • RFA, Alcohol, TACE • High recurrence rate • Liver Transplantation • Best treatment /<67Y / Milan criteria • Molecular Target Therapy - Evolving

  45. RFA + Chemoembolization 61y ♀ HBV+HCC Dx 1/2001 1 3 2

  46. HCC+HBVDx- 1/2001 RFA + Chemoembolization (TACE) RFA 4 RFA TACE RFA C Liver Transplantation 9/2003 Normal liver 2013

  47. HCC – 2009 – Students update Thank you

More Related