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Understanding Hepatocellular Carcinoma (HCC) - A General Intro to Diagnosis and Management-. SIR RFS IO Service Line Created by: Colin Burke 10-22-13. HCC: Pertinent Anatomy. Images from:
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Understanding Hepatocellular Carcinoma (HCC)- A General Intro to Diagnosis and Management- SIR RFS IO Service Line Created by: Colin Burke 10-22-13
HCC: Pertinent Anatomy Images from: Vascular and Biliary Variants in the Liver: Implications for Liver Surgery: Radiographics March-April 2008 28:2 359-378
HCC: Pertinent Anatomy (Cont’d) www.deltagen.comwww.wikipedia.org
HCC: Epidemiology/Risk Factors • 5th most common cancer • Fastest growing cause of cancer mortality • Risk Factors • HBV • HCV • Cirrhosis • Alcoholism • Biliary cirrhosis • Hemochromatosis • NAFLD • Aflatoxins- Esp. in Asian population
HCC: Pathophysiology • Multifactorial, exact mechanism unclear • Inflammation, necrosis, fibrosis, regeneration of cirrhotic liver • Environmental toxins • Mistakes in regenerative pathway • Gene mutations: p53, B catenin • Main Theory • Repeated necrosis & regeneration + genetic material in viral hepatitis = mutations & abnormal cell proliferation www.livingwithcancerinternational.com
HCC: Signs & Symptoms • Jaundice, pruritis • Ascites, • Abdominal Pain • Variceal bleed • Encephalopathy • Paraneoplastic syndromes • Unintentional weight loss Image from: http://www.mcemcourses.org/wp-content/uploads/case9picture.jpg
HCC: Work-up & Diagnosis • Chronic Liver Disease: Screen with US every 6 months • AASLD Guidelines • Asian men over 40 & Asian woman over 50 • Patients with HBV & Cirrhosis • African & North American Blacks • Patients with a family history of HCC • US results • Nodule < 1 cm • Usually not HCC, monitor every 3 months until they disappear • Nodules > 1 cm • Evaluate with CT/MRI • Biopsy only if unable to diagnose on imaging findings • Lab Studies • Nonspecific: • Anemia, thrombocytopenia, increased LFTs, • AFP • Raises concern, especially when over 200 mg/dl
HCC: Basic Imaging Findings • US • Small hypo-echoic lesion • Heterogenous (fibrosis, fatty change & calcifications) • Hard to distinguish from cirrhosis
HCC: Basic Imaging Findings (cont) • CT • Focal, multifocal diffuse, infiltrative or atypical • Hypervascularity in arterial phase, washout in portal and delayed phases • Focal necrosis and calcification (10%) • Capsule (24%)
HCC: Basic Imaging Findings (cont) • MRI • T1 • Variable • Isointense or hyperintense compared to surrounding liver • T2 • Variable, typically hyperintense • Post-gadolinium • Arterial-phase enhancement +/- discrete feeder vessels
HCC: Prognosis • Unresectable: mortality within 3-6 months • Resectable: partial hepatectomycurative due to regenerative nature of liver • 2/3 of the liver can be resected • Role of portal vein embolization prior to partial hepactectomy • IR embolizesthe right portal vein, stimulating hypertrophy of noninvolved lobe & can qualify the patient for resection or bridging to Tx • 5 year survival if resectable: 37-56% • Only 10-20% are completely resectable
HCC: Management Basics • Medical Therapy • Minimally responsive to chemotherapy • Sorafenib (tyr-kinase inhib) used for advanced cases • Mainly Palliative • Lactulose titrated to 2-3 loose stools/day to control encephalopathy in cirrhosis. • Diuretics to control ascites • Antibiotic prophylaxis to prevent SBP • Surgical Therapy • Liver transplant • Resection • Small lesions may be cured under RFA done by IR http://www.ppdictionary.com/viruses/carcinoma_hepatitis_b.jpg
HCC Tx: Role of IR • Unresectable tumors • Increase survival, improve quality of life, currently not intended for cure • Slows progression and is palliative. Also used to help patient’s survive partial hepatectomy or act as a bridge to transplant. • Terminology • Transarterial Chemoembolization: TACE • Radiofrequency Ablation: RFA • Selective Internal Radiation Therapy: SIRT • Portal Vein Embolization: PVE http://www.anes.ucla.edu/images/news/large/DSC02293.jpg
HCC Tx: PVE(Portal Vein Embolization) • Percutaneous transhepatic approach • Embolization of portal vein supplying lobe of liver with the tumor • Compensatory hypertrophy of surviving lobe can qualify patient for resection • Patients initially unresectable due to insufficient remaining normal parenchyma may qualify • Post resection morbidity decreased • Serve as a bridge to transplant Right PVE: http://radiographics.rsna.org/content/22/5/1063/F13.expansion.html
HCC Tx: TACE(TransarterialChemoemobolization) • Selective injection of antineoplasticagent with a radiopaque contrast agent (lipiodol) and embolic agent (gelfoam) • Higher dose of chemotherapy due to decreased systemic exposure • Post Procedure • Post Embolization Syndrome • Hospital stay of 1-3 days • Decreased energy in the following 2 months • Abominal Pain, transaminitis • Follow up CTseveral weeks later to check for tumor response • Repeat TACE • Only 2% of patients have complete response from 1 procedure • Considered non-curative (unlike RFA) • Base repeat treatment on tumor response and hepatic reserve
HCC Tx: RFA(Radiofrequency Ablation) • Destroys tumor using thermal energy from high frequency radio waves • Usually used for small tumors (< 3cm) • US guided percutaneous approach • Post Procedure • Follow up CT/MRI several weeks later to check for tumor response. Can also follow AFP
HCC Tx: SIRT (Selective Internal Radiation Therapy) • Similar to chemoembolization • Uses radioactive microspheres • Radioactive isotope Yttrium (Y-90) incorporated into radioactive spheres • Spheres selectively injected and get lodged in tumor capillaries and proximal vascular supply • Localized brachytherapy • Combined radiation and ischemia results in cell death. • Post Procedure • Post embolization syndrome with fatigue, constitutional symptoms, and abdominal pain • Follow up CT/MRI several weeks later to check tumor response. Can also follow AFP. Return to IR if AFP remains increased. Monitor for variceal bleeds and assessment of underlying liver function. http://www.rwjuh.edu/images/cancer/sirtimage2.jpg
Morbidity and Mortality • TACE • Post Embolization Syndrome • 60-80%of patients • Fatigue, constitutional symptoms, abdominal pain • Symptoms last 3-4 days, full recovery in 7-10 • Liver Failure • Dependent on preprocedure liver function • 20% of patients, irreversible in 6% • Gastroduoenal ulceration • 3-5% • Non target embolization into left gastric • SIRT • Post Embolization Syndrome • 20-55% • Hepatic Dysfunction • RFA • Complications are rare but include abscess formation, subcapsular hematoma and tract seeding • If HCC is not treated • TNM staging: • 5 year survival 55%, 37% and 16% for stage I, II, III respectively • Okuda system: tumor size and degree of cirrhosis • 8.3, 2.0 and 0.7 months for stage I, II, and III respectively
Conclusion/Key Points • HCC: Relatively poor prognosis including both high morbidity and mortality • Main risk factors are chronic liver disease such as HBV, HCV, and cirrhosis • Patients often present with decompensation of chronic liver disease • Medical management generally palliative, aimed at reducing liver disease symptoms, chemotherapy is traditionally ineffective • Surgical resection and transplant can be curative
Conclusion/Key Points • Screen high risk patients with US, f/u with CT/MRI • IR procedures traditionally palliative for unresectable tumors and those patients who are not yet candidates for liver transplant • Growing evidence suggesting increased role for IO therapies • Smaller (<4cm) or solitary lesions managed with RFA • Large or multifocal tumors = TACE or SIRT • Insufficient data for combination RFA and TACE • Efficacy (complicated and conflicting data) • TACE: Objective response: 6-60%. Most studies show increased survival vs conservative treatment • SIRT: Comparable to TACE • RFA: can be curative. 80-90% response for tumors<3 cm • Common complications: Post embolization syndrome and hepatic dysfunction www.barrieronline.com
References • Catalano OA, Singh AH, Uppot RN, Hahn PF, Ferrone CR, SahaniDV.Vascular and Biliary Variants in the Liver: Implications for Liver Surgery: Radiographics March-April 2008 28:2 359-378 • Furuta T, Maeda E, Akai H, Hanaoka S, Yoshioka N, Akahane M, Watadani T, Ohtomo K.. Hepatic Segments and Vasculature: Projecting CT Anatomy onto Angiograms. Radiographics. November 2009 Nov;29(7):1-22. • Madoff DC, Hicks ME, Vauthey JN, Charnsangavej C, Morello FA Jr, Ahrar K, Wallace MJ, Gupta S. Transhepatic portal vein embolization: anatomy, indications, and technical considerations. Radiographics. 2002 Sep-Oct;22(5):1063-76 • Yang ZF, Poon RT. Vascular changes in hepatocellular carcinoma. AnatRec (Hoboken). 2008 Jun;291(6):721-34 • Roche SP, Kobos R. Jaundice in theadultpatient. Am FamPhysician. 2004 Jan 15;69(2):299-304 • Uptodate • Clinical features and diagnosis of primary hepatocellular carcinoma. http://www.uptodate.com/contents/clinical-features-and-diagnosis-of-primary-hepatocellular-carcinoma?source=see_link. Last Updated Sept 23, 2013. Accessed October 20th 2013. • Epidemiology and etiologic associations of hepatocellular carcinoma http://www.uptodate.com/contents/epidemiology-and-etiologic-associations-of-hepatocellular-carcinoma?source=see_link. Last Updated August 30 2013. Accessed October 21, 2013 • Prevention of hepatocellular carcinoma and recommendations for surveillance in adults with chronic liver disease. http://www.uptodate.com/contents/prevention-of-hepatocellular-carcinoma-and-recommendations-for-surveillance-in-adults-with-chronic-liver-disease?source=see_link. Last Updated July 12, 2013. Accessed October 20, 2013 • Surgical management of potentially resectable hepatocellular carcinoma. http://www.uptodate.com/contents/surgical-management-of-potentially-resectable-hepatocellular-carcinoma?source=preview&anchor=H1061867819&selectedTitle=2~150#H1061867819 . Last Updated May 22, 2013. Accessed October 23, 2013 • Nonsurgical therapies for localized hepatocellular carcinoma: Transarterial embolization, radiotherapy, and radioembolizationhttp://www.uptodate.com/contents/nonsurgical-therapies-for-localized-hepatocellular-carcinoma-transarterial-embolization-radiotherapy-and-radioembolization?source=preview&anchor=H1248650314&selectedTitle=1~16#H1248650342 . Last Updated Sept 6 2013. Accessed October 23,2013 • Inteventional Radiology Treatments for Liver Cancer. http://www.sirweb.org/patients/liver-cancer/. Accessed October 2014 • Anatomy of Liver Segments. http://www.radiologyassistant.nl/en/p4375bb8dc241d/anatomy-of-the-liver-segments.html Accessed October 2013
Thank you! Image addapted from: http://www.utmb.edu/surgicalpathology/picts/photo_of_the_month_2006_2007/pom_aug_06.jpg