Case Study Prasun K Jalal MD Baylor College of Medicine
Case no. 1 • 53/M, Caucasian • Fatigue and lower extremity swelling- 6 m • H/O IV drug use in 1970’s • Drinks 2-3 beer a day for 20 yrs, stopped 6 m back
Examination • BMI 35 • Spider angioma on chest • Hepatosplenomegaly • Trace pedal edema both legs
Labs • Bili 2 (direct 0.5), Al Phos 70, AST 57, ALT 32, Alb 2.8, TP 7 • WBC 3.8, Hb 14, Platelet 84 • Creatinine 0.9, INR 1.2 • MELD=11 • HCV 1.1 million IU/ml, Genotype 1a
Q1. What would you do next? • Liver Biopsy • US abdomen, screen for esophageal varices and Refer to a transplant center • Contrast enhanced CT scan or MRI, screen for esophageal varices and Refer to a transplant center \ • Serum AFP, screen for esophageal varices and Refer to a transplant center • Treat for Hepatitis C
MRI 10/31/12 T2 Pre Arterial Equilibrium Venous
Dual Blood Supply of Liver • The vascular supply of HCC arises from the hepatic artery through neovascularization. • Imaging of the liver has to be performed in a triple phase manner to account for the early arterial phase followed by the portal venous phase and the delayed phases Yu JS et al. Am J Roentgenol 1999
Washout in HCC Washout in HCC Arterial phase 2-min delayed Arterial phase 5-min delayed
HCC: Perfect Storm NASH HCC HBV HCV
Liver Cancer Has the Fastest Growing Death Rate in the US Trends in US Cancer Mortality Rates All Other Cancers (Average) Corpus & Uterus, NOS Testis Lung & Bronchus (Female) Esophagus Thyroid Liver Annual Percent Change (1994-2003)* *Represents the annual percent change over the time interval National Cancer Institute Website. Available at: http://seer.cancer.gov/csr/1975_2003/sections.html. Accessed September 21, 2006.
HCV Cirrhosis and HCC HCV Cirrhosis and HCC (2-8% per year) Multiple smallfoci of HCC
Groups for whom HCC surveillance in recommended or in whom the risk of HCC is increased, but in whom efficacyof surveillance has not been demonstrated- AASLD 2010 Surveillance recommended • Asian male hepatitis B carriers over age 40 • Asian female hepatitis B carriers over age 50 • Hepatitis B carrier with family history of HCC • African/North American Blacks with hepatitis B • Cirrhotic hepatitis B carriers • Hepatitis C cirrhosis • Stage 4 primary biliary cirrhosis • Genetic hemachromatosis and cirrhosis • Alpha 1-antitrypsin deficiency and cirrhosis • Other cirrhosis Surveillance benefit uncertain • Hepatitis B carriers younger than 40 (males) or 50 (females) • Hepatitis C and stage 3 fibrosis • Non-cirrhotic NAFLD
AASLD Recommendations for HCC surveillance: Surveillance for HCC should be performed using ultrasonography (level II). Patients should be screened at 6 month intervals (level II). The surveillance interval does not need to be shortened for patients at higher risk of HCC (level III).
Q2. What would you do next? • Biopsy the lesion • Refer to oncology-Chemotherapy with Sorafenib (Nexavar) • Surgical Resection of tumor • Evaluate for liver transplantation
AASLD Guidelines for Diagnosis of HCC Liver Nodule (screening US) Growing/ Stable Changing Character Typical features of HCC = Hypervascularity on arterial phase AND washout in venous or delayed phases
Surgical Resection In cirrhosis Surgical Resection: Indications • Child-Pugh A cirrhosis • No clinically significant portal hypertension • Bilirubin < 1 mg/dl • Plus: same criteria as in non-cirrhotics: • No macrovascular, lymph node, or extrahepatic metastases • Technical feasiblity • Tumors of any size
100 No Portal pressure, Bili <1 80 Portal pressure, Bili <1 60 Probability (%) 40 20 Portal pressure, Bili 1 0 0 20 40 60 80 Months Outcomes of Surgical Resection for HCC in Patients with Cirrhosis Patients selected by Mazzaferro Criteria and Child’s A cirrhosis Llovet Hepatology 1999
20 - 70% 0 - 43% Resection vs. Transplant for HCC Three Year Recurrence Rates Author / Year Number Recurrence Resection Transplant Resection Transplant Iwatsuki 1991 76 105 50% 42.9% Michel 1995 20 21 70% 14.3% Vargas 1995 35 11 40% 0% Tan 1995 12 15 25% 20% Otto 1998 52 50 53.8% 36.0% Llovet 1999 77 87 33.8% 2.3% Weimann 1999 32 31 18.8% 0% Figueras 2000 35 85 65% 0% DeCarlis 2001 154 121 47.4% 9% Overall Wong LL, Amer J Surgery 2002
Resection vs. OLT vs. Ablation Recent citations 1995-2001 Resection vs. OLT vs. Ablation Survival 1 yr 5 yr • Resection 74-96% 25-72% • OLT 84-90% 69-75% • Ablation 87-98% 29-54% Bruix and Llovet, Hepatology 2002
Liver Transplantation for Small HCC: Milan Criteria Liver Transplantation for HCC: Milan Criteria • Patients with cirrhosis and HCC • Single tumors ≤ 5 cm or no more than 3 nodules, each ≤3 cm • No macrovascular invasion • No distant metastases • 75% 4-year survival, 83% recurrence-free • 27% exceeded criteria on path review • 50% 4-year survival, 59% recurrence-free Mazzafero, et al, NEJM 1996
UNOS Criteria for Liver Transplantation for HCC • A candidate with an HCC tumor that is stage T2 may be registered at a • MELD/PELD score equivalent to a 15% probability of candidate death within 3 months. Stage T2 lesions are defined as • - 1 lesion >= 2 cm and <= 5cm; OR • 2 or 3 lesions, >= 1cm and <= 3cm in size. • Rule out any extrahepatic spread (i.e. lymph node involvement) and/or macrovascular involvement (i.e., tumor thrombus in portal or hepatic vein) with dynamic contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI). • The assessment of the candidate prior to transplant listing must include a CT of the chest that rules out metastatic disease. • The candidate must not be eligible for resection. • The alpha-fetoprotein level is required for all HCC exception applications.
Expanding the Criteria for Liver Transplantation: UCSF Criteria 2001 Expanding the Criteria for Liver Transplantation: UCSF Criteria 2001 1 • Solitary lesion • 6.5 cm • Multiple • 3 nodules • Largest 4.5 cm • Total tumor diameter 8 cm Within criteria 0.8 0.6 Survival Distribution Function 0.4 Outside criteria 0.2 0 0 1 2 3 4 5 Years After Liver Transplantation Meet New Staging Criteria Yes: 60 49 37 25 20 16 No: 10 5 4 2 1 0
Local Ablation Therapy for Transplant Candidates Local Ablation Therapy for Transplant Candidates • Can serve as “bridge” to transplant • Minimally invasive • Provides effective control of the tumor up to 1-2 year from the treatment • Additional benefit from tumor reduction prior to transplantation
Q 3. What Loco-regional therapy you would recommend? • Percutaneous Ethanol Injection (PEI) • Radiofrequency ablation (RFA) • TransarterialChemoebmolization (TACE) • Radioembolization for Hepatocellular Cancer Using Yttrium-90
Trans-arterial Radioembolization for Hepatocellular Cancer Using Yttrium-90 Impregnated Glass Microspheres • Evaluate hepatic arterial anatomy • Occlude any branches supplying extrahepatic structures • Infuse Tc-99m-macroaggregated albumin • confirm perfusion limited to the liver • measure the lung shunt (<16.5 mCi Y-90 to the lungs)
Result of Microsphere Radioembolization Pre-Microsphere Post-Microsphere
Radiofrequency Ablation for Hepatocellular Carcinoma Deployment of tines and treatmentof tumor and surrounding region Probe insertion
A cohort Study of RFA demonstrated that complete ablation of lesion smaller than 2 cm is possible in more than 90% cases with a local recurrence rate of less than 1% McMahon BJ, Bulkow L, Harpster A, Snowball M, Lanier A, Sacco F, Dunaway E, et al. Hepatology 2000;32:842–846.
MRI 3/18/2013 Arterial T2 Pre Equilibrium Venous
Molecularly targeted agents in advanced hepatocellular carcinoma: Sorafenib (Nexavar)
Phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) Trial Lovet J, et al. J Clin Oncol (Meeting Abstracts). 2007; 25(18S). Abstract LBA1
Factors Determining Prognosis of Hepatocellular Cancer Factors Determining Prognosis of Hepatocellular Cancer • Tumor stage • - Size - Vascular invasion • - Number - Extrahepatic spread • - Location • Liver function • Overall patient health • Performance status: Karnofsky score • Intervention-specific outcome Hepatocellular Cancer is a curable disease!
A proposed algorithm for treatment of HCC (adapted from BCLC algorithm) Gastroenterology, May 2008
Management of Hepatocellular Carcinoma Requires a Multidisciplinary Approach:Baylor/St Luke’s Team Hepatobiliary Surgery J Vierling N sussman R Stribling P Jalal G Sood K Hussain S Khaderi B Hollinger L Camacho P Holoye A Kaseb Hepatology Oncology J Goss C O’mahony M Round M Skolkein B Toombs J Fisher Pathology Radiology R Shannon St Luke’s Center for Liver Diseases