SIR RFS IO Service Line

Created by: Colin Burke

10-22-13

Understanding Hepatocellular

Carcinoma (HCC) - A General Intro to Diagnosis and

Management-

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HCC: Pertinent Anatomy

Images from:Vascular and Biliary Variants in the Liver: Implications for Liver Surgery: Radiographics March-April 2008 28:2 359-378

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HCC: Pertinent Anatomy (Cont’d)

www.deltagen.com www.wikipedia.org

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5th most common cancerFastest growing cause of cancer mortalityRisk Factors

HBVHCVCirrhosisAlcoholismBiliary cirrhosisHemochromatosisNAFLDAflatoxins- Esp. in Asian population

HCC: Epidemiology/Risk Factors

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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

HCC: Pathophysiology

www.livingwithcancerinternational.com

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Jaundice, pruritisAscites, Abdominal PainVariceal bleedEncephalopathyParaneoplastic syndromesUnintentional weight loss

HCC: Signs & Symptoms

Image from: http://www.mcemcourses.org/wp-content/uploads/case9picture.jpg

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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: Work-up & Diagnosis

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US Small hypo-echoic

lesion Heterogenous (fibrosis,

fatty change & calcifications)

Hard to distinguish from cirrhosis

HCC: Basic Imaging Findings

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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)

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Classification of HCC on CT

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MRIT1

VariableIsointense or

hyperintense compared to surrounding liver

T2Variable, typically

hyperintense

Post-gadoliniumArterial-phase

enhancement +/- discrete feeder vessels

HCC: Basic Imaging Findings (cont)

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Unresectable: mortality within 3-6 monthsResectable: partial hepatectomy curative due

to regenerative nature of liver2/3 of the liver can be resected

Role of portal vein embolization prior to partial hepactectomyIR embolizes the 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: Prognosis

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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

HCC: Management Basics

http://www.ppdictionary.com/viruses/carcinoma_hepatitis_b.jpg

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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

HCC Tx: Role of IR

http://www.anes.ucla.edu/images/news/large/DSC02293.jpg

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Percutaneous transhepatic approach

Embolization of portal vein supplying lobe of liver with the tumor

Compensatory hypertrophy of surviving lobe can qualify patient for resectionPatients initially unresectable

due to insufficient remaining normal parenchyma may qualify

Post resection morbidity decreased

Serve as a bridge to transplant

HCC Tx: PVE(Portal Vein Embolization)

Right PVE:http://radiographics.rsna.org/content/22/5/1063/F13.expansion.html

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Selective injection of antineoplastic agent 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 CT several 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: TACE (Transarterial Chemoemobolization)

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Destroys tumor using thermal energy from high frequency radio waves

Usually used for small tumors (< 3cm)

US guided percutaneous approach

Post ProcedureFollow up CT/MRI several

weeks later to check for tumor response. Can also follow AFP

HCC Tx: RFA(Radiofrequency Ablation)

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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.

HCC Tx: SIRT (Selective Internal Radiation Therapy)

http://www.rwjuh.edu/images/cancer/sirtimage2.jpg

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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

Morbidity and Mortality

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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

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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

Conclusion/Key Points

www.barrieronline.com

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Catalano OA, Singh AH, Uppot RN, Hahn PF, Ferrone CR, Sahani DV.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. Anat Rec (Hoboken). 2008 Jun;291(6):721-34

Roche SP, Kobos R. Jaundice in the adult patient. Am Fam Physician. 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 radioembolization http://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

References

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Thank you!

Image addapted from: http://www.utmb.edu/surgicalpathology/picts/photo_of_the_month_2006_2007/pom_aug_06.jpg