Hepatocellular carcinoma

Shaukat Khanum Memorial Cancer Hospital and Research Centre
Jibran Mohsin
Hepatocellular Carcinoma
Fellow Surgical Oncology

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Outline
Introduction Fibrolamellar carcinoma (FLC)
Incidence Screening
Risk factors Staging systems
Pathology Treatment options
Clinical presentation Defining treatment strategy
Investigations Summary
Diagnosis

Introduction
 90 % of primary liver malignancy
 6th most common neoplasm (> 5% of all cancers)
 5th most common malignancy (men)
 9th most common malignancy (women)
 2nd most common cause of cancer-related deaths
 745 000 deaths worldwide (9.1 % of total; 2012)

Introduction
 Cause of death
 Cancer – 50-60 %
 Hepatic failure – 30 %
 GI bleed – 10 %
 Screening of high risk patients, HCC can be identified
early

Incidence
 World age adjusted incidence (male)
 14.9 / 100 000 (780,000 cases annually)
 Geographical variation
 HBV/HCV; > 75 % cases
 99 / 100 000 (Mongolian men)
 Eastern and SE-Asia (> 20 cases / 100 000)
 Southern Europe and north America (intermediate incidence)
 Northern Europe and south central Asia ( < 5 cases / 100 000)
 HCV, Alcohol, NAFLD, obesity

Incidence
 Increasing incidence
 From late 1960s-70s (young- HCV – IVD use- blood
supplies) to early 1990s (screening)
 Better medical management of cirrhosis, increased
survival
 Ageing of populations
 Increased detection
 Epidemic of obesity and type II diabetes

Risk factors
 Main risk factor
 Cirrhosis
 Additional independent risk factors
 Male gender
 Age (marker of duration of exposure to etiological agent)
 Stage of cirrhosis
 Diabetes

Cirrhosis vs no underlying liver disease
Cirrhosis Absence of cirrhosis (≠ Normal liver)
80-90 % HCC 10-20 %
Mild fibrosis
Necro- inflammation
Steatosis
Liver cell dysplasia
Chronic Viral Hepatitis (highest risk) Conditions associated with cirrhosis
• HBV infection or alcohol abuse
• α 1 antitrypsin deficiency
• Hemochromatosis
Primary biliary cirrhosis Conditions not associated with cirrhosis
• Hormonal exposure
• glycogenosis

Chronic HBV infection
 Most frequent and direct risk factor worldwide (> 50 %
of all cases)
 40 million infected
 HBV-DNA sequences integrate in genome of malignant
hepatocytes
 HBV-specific protein interact with liver genes
 +/- cirrhosis

 Risk of HBV-associated HCC
 Severity of underlying hepatitis
 Age at infection (hence duration of infection)
 Level of viral replication
 10-fold risk HBsAg vs 60 fold risk HBeAg
 HBV-DNA copies/mL > 104 (2.3 risk) vs > 106 (6.1 risk)

 Cumulative risk (5 year)
 10 % (western) vs 17 % (Asian)
 Vertical transmission > horizontal (sexual or parenteral)
 Longer duration
 Additional environmental factors

HCV infection
 Accounts for major proportion of increase in HCC over
last 10 years
 > 70% HCC (west) : anti-HCV antibodies
 Mean time around 30 years
 Most frequent and 1st complication in HCV
compensated cirrhosis
 0-2 % (chronic hepatitis) vs 1-4 % (7 % Japan)
(compensated cirrhosis)

Additional Risk/co- factors
Chronic HBV infection HCV infection NAFLD HH
Male gender (3-6 times
higher)
Male gender (2-3 X) Male gender Male gender
Age > 40 years Age > 55 years (2-4 x) Increasing age Age > 55 years ( 13.3 fold)
Concurrent HCV infection
(2 x)
HBV coinfection (2-6 x) HBV infection (4.9 fold)
HDV coinfection (3x) HIV-HCV ( 15-20 years
earlier)
Heavy alcohol use (2-3 x) Alcohol > 60-80 g/day (2-4
x)
Alcohol abuse (2.3 fold)
Aflatoxins (endemic
regions)
Iron deposition
Diabetes ( 2 x) diabetes
Obesity (NAFLD)
≠ HAV/ HEV ≠ viral genotype / viral
concentration
Severity of liver disease

Future
HBV HCV NAFLD
Prevention of
HBV infection
Prevention of HCV infection Growing epidemics worldwide
Immunization Prevention of progression of HCV
chronic infection to cirrhosis
• Direct acting anti-virals
(90% cure)
• Sustained virological
response

HIV infection
 Due to higher prevalence of associated well-known risk
factors
 Co-infection HBV/HCV
 Alcohol abuse
 NASH
 Diabetes
 25 % o all liver-related deaths
 Earlier and more aggressive course (HIV-HCV vs HCV
alone)

Alcohol
 Heavy (> 50-70 g/day) and prolonged use
 Classical risk factor
 Annual Incidence
 1.7 % alcohol cirrhosis
 2.2 % HBV cirrhosis
 3.7 % HCV cirrhosis
 Additional risk factor in HBV/HCV cirrhosis/
metabolic syndrome related chronic liver disease

Non-alcoholic fatty liver disease (NAFLD)
 Simple steatosis  NASH (cirrhosis)
 Metabolic syndrome (epidemic)
 Type II diabetes
 Central obesity
 Dyslipidemia
 25 -33 % metabolic syndrome: Cirrhosis
 4-27 % of above : HCC (surgical series: 6-10 %)
 4 x increased indication for transplantation (2002-2012) vs
HCV

 Obesity:
 Increase mortality from liver cancer far more than any other
cancer
 Diabetes
 Increase risk of HCC +/- acute and chronic liver disease

 Male gender
 Increasing age
 60 % cases > 50 years with DM/obesity
 NASH/advance liver fibrosis
 Sinusoidal iron deposition
 Severity of underlying liver disease
 Synergistic effect with chronic HCV infection or
alcoholic consumption

Hereditary hemochromatosis (HH)
 ART
 Homozygosity of C282Y mutation in hemochromatosis
gene
 Excessive GI iron absorption
 Others iron overload conditions
 Homozygous beta thalassemia (African overload syndrome)

Cirrhosis of other etiologies
 Primary biliary cirrhosis (PBC)
 Low risk factor (rare incidence, M:F 1:9)
 Secondary biliary cirrhosis (exceptionally rare)
 Autoimmune hepatitis (low risk: female predominance,
delayed development of cirrhosis due to steroids)
 Cirrhosis at time presentation
 HCV may induce autoantibodies

Aflatoxin B1
 Asia and sub-Saharan Africa
 Contamination of imperfectly stored staple crops by
Aspergillus flavus
 Tumor suppressor gene p53 mutation
 Independent risk factor vs co-carcinogen (HBV)
 Frequently non-cirrhotic liver

Metabolic liver disease
Increased risk Low risk
Alpha 1 anti trypsin deficiency Glycogenosis type IV
Porphyria cutanea tarda Hereditary fructose intolerance
Tyrosinemia Wilson disease
(oxygen/nitrogen species and
unsaturated aldehydes ; p53 mutation)
Hypercitrullinemia

Hepatocellular Adenoma (HCA)
 Malignant transformation via Hepatocyte dysplasia
 Adenomatosis: not increased risk
Female Male
≥ 4 cm As small as 1 cm
Child bearing age with prolonged use OCP/estrogens Make with metabolic syndrome
4.2 % risk 50 % risk (10 x)
Discontinuation doesn’t completely avoid risk
Resection if > 4 cm Resection /ablation irrespective of size

Hepatocellular Adenoma (HCA)
 Risk factors
 Phenotype: Telangiectatic or atypical > Steatotic
 Genotype: β catenin (10-15 % HCAs)
 Type I glycogenosis
 Use of anabolic steroids (recreational) or androgens
 Fanconi syndrone

Pathology (Preneoplastic lesions)
(Microscopic)
dysplastic foci
Macroscopic dysplastic nodules (DNs)
Dysplastic hepatocytes
(< 1mm size)
Nodular region < 2 cm (diameter) with dysplasia (but without definite
histological criteria of malignancy)
Chronic liver disease
(cirrhosis)
Degree of cytological or architectural atypia
Low grade DNs High grade DNs (less common)
(33 % malignant transformation)
~ 1 cm Up to 2 cm
Slightly yellowish Increased cell density
Very low chance of malignancy Irregular thin-trabecular pattern
Unpaired arteries
Distinct foci of well differentiated
HCC
Difficult to differentiate vs well
differentiated HCC

Pathology (HCC)
 Subdivisions
 Gross morphology
 Degree of differentiation
 Vascularity
 Capsule
 Vascular invasion

Pathology
 Gross Morphology
Solitary
Multinodular Multicentric Synchronous discrete lesions in different segments
Intrahepatic
metastases
1 dominant mass and number of ‘daughter‘ nodules
in adjacent segments
Diffuse Relatively rare
Poorly defined widely infiltrative masses
Diagnostic challenges on imaging
Infiltrating Less differentiated
Ill defined margins
Fibrolamellar Young, without cirrhosis, better prognosis, cure by
resection

Pathology
 Degree of Differentiation
 Decreases with increase in diameter
 Grade 1: resemble normal hepatocytes, near normal lobar
architecture
 Imunomarker (50-73 %): Glypican 3 (GPC3), Heat Shock
Protein 70 (HSP70) and Glutamine Synthetase (GS)
 100 % specificity on resected specimens
Edmondson grade (Histologic Grade (G))
Grade can’t be assessed GX
Well differentiated G1
Moderately differentiated G2
Poorly differentiated G3
Undifferentiated G4

Pathology
 Molecular Pathogenesis
 TERT promoter mutations (most frequent i.e. 60 %)
 Subsequent increase in telomerase expression
 Development/transformation and progression
 Prognosis/select treatment/assess response to chemotherapy

Pathology
 Vascularity
 Macroregenerative nodule  low grade DN  High grade
DN  Frank HCC
 Loss of visualization of portal tracts
 Development of new non-tiadal arterial vessels (arterial
neoangiogenesis)
 Dominant blood supply of overt HCC lesion
 Landmark of HCC diagnosis
 Rationale for chemoembolization and anti-angiogenic
treatment

Pathology
 Distinct fibrous capsule
 80 % resected HCCs
 Variable thickness
 May not be complete
 Frequently infiltrated by tumor cells
 Microscopic capsular invasion:
 33 % cases in tumor < 2 cm diameter
 66 % cases in larger tunors

Pathology
 Vascular invasion
 Portal invasion (most important predictive factor of recurrence)
 Expansive type
 Poorly differentiated
 Large size
 Microscopic vascular invasion
 20 % (< 2cm)
 30-60 % (2-5 cm)
 60-90 % ( > 5 cm)

Pathology
 Vascular (Portal) invasion
 Tumor thrombus has its own arterial supply
 Mainly from site of original venous invasion
 Grows rapidly in both direction (in particular towards main portal vein –
 high risk of complete thrombosis and increased portal HTN –
 fatal esophageal varices rupture/ liver failure i.e.
ascites/jaundice/encephalopathy
 Tumor fragments spread throughout liver as thrombus crosses
segmental branches

Pathology
 Vascular invasion
 Hepatic veins
 Possible although less frequent
 Extends into supra hepatic vena cava or right atrium
 Lung metastases
 Biliary tract invasion (rare)
 Jaundice or hemobilia

Pathology
HCC induced biliary obstruction
Intraductal tumor extension
Obstruction by fragment of necrotic tumor debris
Hemorrhage of tumor (Hemobilia)
Metastatic lymph node compression of major bile ducts in porta hepatis.
Rate of invasion
Portal vein invasion 15 % (1 in 3 cases will develop PV thrombosis)
Hepatic vein invasion 5 %
Bile duct invasion 3 %

Pathology
Metastases
Sites (descending order) Lungs (most frequent)
Adrenal glands
Bones
Lymph nodes
Meninges
Pancreas
Brain
Kidney
Risk factors Tumor size
Bilobar disease
Poor differentiation

Clinical Presentation
 Rare before 40 years, peak at 70 years
 M:F (2-4:1)
 most pronounced in medium risk south European populations
and premenopausal women
 Difference in exposure to risk factors
 Higher BMI
 Higher levels of androgenic hormones

Circumstances of diagnosis
Incidental finding During routine screening (Industrialized countries)
During assessment of patients with deranged LFTs or of another
pathological condition
Symptomatic
(severity)
Liver-related (functional status of non-tumorous liver)
• Sudden onset or worsening ascites or liver decompensation
may be 1st evidence of HCC
Cancer-related ( stage of tumor)
• Abdominal pain
• Malaise
• Weight loss
• Asthenia
• Anorexia
• Fever
• Acute (tumor extension or complication- next slide)

Spontaneous Rupture • 5-15 % cases
• Superficial or protruding tumors
• Suspect:
• Known HCC/cirrhosis + acute epigastric pain or
• Asian/African men with acute abdomen
• Minor rupture:
• Abdominal pain
• Hemorrhagic ascites
• Hypovolemic shock (50 % cases)
PV invasion Upper GI bleed
Acute ascites
Hepatic vein or IVC
invasion
PE
Sudden death
Biliary invasion/ Hemobilia
(2 %)
2 % cases
Paraneoplastic syndromes Polyglobulia, Hypercalcemia, Hypoglycemia

Clinical Presentation (examination)
 Large or superficial tumors
 Clinical signs of cirrhosis
 Ascites
 Collateral circulation
 Umbilical hernia
 Hepatosplenomegaly

Investigations
Hematological Liver function tests
Serum tumor markers Alpha-fetoprotein (AFP)
DCP
PIVKA-II
AFP-L3
Radiological Ultrasound
CT scan
MRI
Contrast enhanced US
Angiography
PET
Pathological Cytology
Histology

Liver function tests (LFTs)
 Non-specific
 Reflects underlying pathology or presence of SOL
 Normal LFTs exceptional;
 HCC in background of cirrhosis
 HCC in normal liver are large
 Jaundice most frequently result of liver decompensation

Serum Alpha fetoprotein (AFP)
 Most widely recognized serum marker of HCC
 Normal: 0-20 ng/mL
 May increase in HCC
 > 400 ng/mL (diagnostic of HCC ; 95 % accuracy)
 > 10 000 ng/mL (5-10 % cases)
 Poor differentiation
 Tumor aggressiveness
 Vascular invasion

Serum Alpha fetoprotein (AFP)
 Sensitivity
 > 20 ng/mL (60 %)
 > 200 ng/mL (78%)
 Others
 Non –tumor: 30 % chronic active hepatitis without HCC
 Tumor:
 Non-seminal germinal tumors, Hepatoid gastric
tumors, NET

Other serum tumor markers (Japan)
 Des-γ-carboxy prothrombin (DCP)
 Sensitivity (early detection)
 61% (AFP alone)
 74 % (DCP alone)
 91% (AFP + DCP)
 Prothrombin induced by vitamin K absence (PIVKA-II)
 > 40 mAU/mL
 AFP-L3 (> 15 %)

Radiological
 Objective
 Screen high risk patients for development of HCC (US)
 Differentiate potential HCC from other tumors/SOL
 Hyper vascularity during arterial phase
 ‘Washout’ during portal or late phase (Hypo vascular
compared to adjacent parenchyma)
 Select appropriate treatment
 Number, size, extent, daughter nodules, vascular invasion,
extrahepatic spread and underlying liver disease.

Ultrasound
 1st line investigation for screening
 Low cost, availability, sensitivity
 Accuracy
 3-5 cm: 85-95 %
 1 cm: 60-80 %
 steatosis rates and heterogeneity of underlying liver disease
 Dimension and location
 Operator experience
 Echogenicity

Ultrasound
 Echogenicity
 Small HCC: hypoechoic and homogenous (regenerating/DNs)
 Large HCC: Hypo/hyperechoic but heterogeneous
 Capsule: Hypoechoic peripheral rim

Ultrasound (Demerits)
 Infiltrative type difficult: Grossly heterogeneous
cirrhotic liver
 1 cm tumor: deep vs surface
 Upper segments or edge of left lateral segments
 Obesity (abdominal wall and steatotic liver)

Ultrasound
 Doppler US: feeding artery +/- draining vein
 Vascular invasion or biliary invasion
 Indirect evidence of cirrhosis
 Segmental atrophy, splenomegaly, ascites, collateral veins

Helical / Multislice spiral / multiphasic CT
 More accurate than US
 Multiphasic
 Without contrast
 With Contrast:
 Arterial (25-50s)
 Portal (60-65s)
 Equilibrium (130-180s)

CT scan: Role
 HCCs identification and distribution (lobar/segmental)
 Features of underlying cirrhosis
 Liver/tumor volumes
 Extrahepatic tumor spread
 Vascular invasion of segmental branches

CT scan: features
 Usually hypodense
 Spontaneous hyperdense (2-20%): iron overload or
fatty infiltration
 Early uptake of contrast with mosaic shape pattern
 Sharply diminished density in portal phase
 Washout during late phase

CT scan: features
 Variable vascularity depending on tumor grade
 Capsule: Peripheral enhanced thickening in portal or
late phase
 Intratumoral arterioportal fistula
 Early enhancement of portal branches
 Triangular area distal to tumor with contrast enhancement
different from adjacent parenchyma

MRI
 More accurate than other imaging techniques
 HCC vs other liver tumors (> 2cm)
 T1- and T2-weighted images
 Early, intermediate and late phases (gadolinium)
 Features:
 Mosaic shape structure
 Capsule

MRI
 Early uptake and late washout
 Gd-EOB-DTPA
 liver specific MR contrast medium
 Accumulates in Kupffer cells (phagocytosis) or hepatic cells
 Increased MRI accuracy
T1 weighted T2 weighted
Hypodense Hyperdense 54 % cases
Hypodense Hypodense 16 % cases
Hyperdense Fatty/copper/glycogen infiltration of tumor

Contrast-enhanced US (CEUS)
 Most recent technique to assess vascularization
 Contrast agent (stabilized microbubbles) : IV bolus
injection followed by saline flush
 Arterial (10-20s post injection)
 Portal venous (30-80s)
 Late (120-360s)

 Merits
 Greater sensitivity to detect arterial enhancement
 microbubbles confined to vascular spaces
 Continuous monitoring of images
 Well differentiated vs poorly differentiated: slower wash out
 Demerits
 Same as other US modes

 Sonazoid-CEUS (Japan 2007; 2nd generation US
contrast agent) vs Sono Vue
 Taken up by Kupffer cells in postvascular/Kupffer
phase (10 mins post injection)
 Extremely stable Kupffer images suitable for repeated
scanning 10-120 mins after injection

Angiography
 As part of arterial chemoembolization
 Arteriography: early vascular uptake (blush)
 Lipiodol (radiodense) injection
 Retained: HCC, focal nodular hyperplasia, adenoma,
angioma, metastases
 False-negative: Avascular, necrotic or fibrotic HCC

18F-FDG-PET
 Limited role
 low sensitivity (60 %)
 Can detect poorly differentiated, but not well differentiated
 Similar metabolism
 18F-fluorocholine (FCH), PET tracer of lipid metabolism
 High sensitivity and more suitable than CT or bone scan
for bone metastases in metastatic HCC

Accuracy
 Contrast CT +/- MRI
 Highest diagnostic accuracy (> 80 %)
 Nodules < 1cm
 3 monthly surveillance for at least 2 years
 Nodules > 1 cm
 Suspicious
 Typical HCC features: no further investigations
 Not typical: Percutaneous FN biopsy

Pathological (cytology/histology)
 Increased accuracy: if non-tumorous tissue is available
 Demerits
 Hemorrhage
 Pain
 Needle tract neoplastic seeding (1-5 %)
 Limited to subcutaneous tissue
 Slow progression
 Local excision without impact on survival
 Vascular spread

 Risk of needle tract seeding vs risk of aggressive
treatment (resection/transplantation) in cases without
malignancy
 Avoid direct puncture of nodule
 Through thick area of normal liver
 GPC3, HSP70, GS staining (small lesions not clearly
HCC)

 Low false-positive rate
 High false-negative rate
 Small lesions
 Lesions difficult to access
 Lesions in multinodular parenchyma

Diagnosis
 Standard for diagnosis: Histology
 Tumors < 3 cm
 Active treatment is required
 Non-invasive diagnosis (radiological imaging alone)
 Rigorous technique and interpretation

Diagnostic criteria
 European Association for the Study of the Liver
(EASL)
 2000 (1st attempt), 2011 (updated)
 AFP: lack adequate sensitivity and specificity
 Based on imaging +/- biopsy

Diagnostic criteria
Nodule size
(screening US)
< 1 cm • Repeat US at 3-6 monthly (until lesion
disappeared/enlarged/HCC features) for at least 2 years
• Other imaging techniques unlikely to reliably confirm
diagnosis
• Accuracy of liver biopsy and likelihood of HCC is low
• Than routine surveillance
>1 cm with
cirrhosis
Early uptake and delayed wash out on a single dynamic imaging
study (triphasic CT or MR with gadolinium)= characteristic of HCC
(Sensitivity 71 %, PPV 100 %, Specificity 100 %)
> 1 cm without
cirrhosis Diagnostic biopsy (negative result doesn’t rule out malignancy)
Vascular features
not typical

Diagnostic criteria
 Biopsy of small lesions
 Expert pathologists
 Not clearly HCC: CD34, CK7, GPC3, HSP-70, GS
 Negative biopsy
 Imaging 3-6 monthly
 If enlarges but atypical of HCC: repeat biopsy

Diagnostic criteria
 CEUS
 False-positive HCC diagnosis
 HCC vs intrahepatic cholangiocarcinoma
 Withdrawn from diagnostic algorithm (American association
for the study of Liver Disease – AASLD)

Fibrolamellar carcinoma (FLC)
 Prognosis better than overall HCC
 5 year SR (50-75%) following resection
 Resection preferred over transplantation
 Imaging
 Large solitary hyper vascular heterogeneous liver mass
 Central hypo dense region/scar (central necrosis/fibrosis)
 Low attenuation on MRI T2 images vs high attenuation of central scar
of focal nodular hyperplasia
 Well defined margins and calcification (68 %)

 High AFP: < 10 % cases
 Lymphadenectomy recommended if resection considered
 Rationale: LN invasion within hepatic pedicle (60%)
 Significant risk of recurrence
 Liver, LN or distant
 Close long-tern follow up mandatory
 Recurrence /death beyond 5 years common
 Repeat resection reasonable options: young population, indolent course, relative inefficacy
of non surgical treatments

 True FLC vs mixed FLC-HCC
 “Conventional HCC displaying some distinct area with FLC features”
 Transplantation: alternate option in selected cases
 Survival rate 48 %

Screening
 Routinely done in countries where effective therapeutic interventions are
available
 Fulfill most of criteria for surveillance /screening program
 Common in highly endemic areas (increasing incidence in others)
 High mortality
 Extremely poor survival by time patients present with cancer-related symptoms
 Population at risk is clearly defined (male, > 60 years, HBV/HCV)
 Effective treatment available in selected patients
 Acceptable screening tests:
 low morbidity and high efficacy
 Allow tumor detection in latent/early stage

Screening
 Diagnosis at early stage required with preserved liver function
At presentation
Symptomatic Median survival (6 months)
Asymptomatic untreated (not end-stage) 3 year survival (50%)

Screening
 AFP
 Little value in screening alone
 Normal baseline AFP  increased AFP and normal US  CT/MRI
 Ultrasound
 Difficult in obese patients with fatty liver disease and cirrhosis
 Optimal interval for periodic screening (6 monthly; 3-4 months in Japan) in high risk
patients
 Tumor doubling time vary widely (average 200 days)
 Undetectable to 2 cm (4-12 months)
 Rapidly growing HCC to reach 3 cm ( 5 months)
 Treatment most effective for tumors < 3 cm

Screening
 Impact on prognosis
 China on HBV carriers
 Cost effective if expected HCC risk exceeds
 0.2 % per year in HBV patients
 1.5 % per year in HCV patients

Screening
 Limitations
 20-50 % HCC at presentation had previously undiagnosed cirrhosis
(escape surveillance)
 Access to medical care
 Compliance: 50 % drop out in 5 years (alcoholic cirrhosis)
 US: operator dependent
 CT/MR:
 High cost/invasiveness, unsuitable for regular screening
 Suitable in irregular liver parenchyma or obesity
 Decision to screen cirrhotic patient: consider comorbid disease, severity of
liver disease and available treatment options (e.g. no screening in CP C if
not candidate for LT)

Screening (Summary)
 US recommended as screening tool, whereas CT/MRI most useful in
confirming diagnosis
 High risk groups
 Established cirrhosis (HBV/HCV/Hemochromatosis)
 CLD due to NASH
 Male, alcohol related cirrhosis abstaining from alcohol or likely to comply
with treatment
 Surveillance of at-risk patients at 6 monthly interval with US to detect HCC a
early stage

Staging systems
 Objective
 Predict outcome / prognosis / survival
 Select treatment plan

Staging systems
Parameters affecting survival
Morphological spread of tumor • Number of tumor nodules
• vascular invasion (radiological or
microscopically)
• Tumor size (dominant nodule)
• Limitation: based on pathological findings;
applicable on resected specimens accurately
only
Presence and severity of cancer –
related symptoms
• WHO performance status or Karnofsky index
• Pain (poor outcome indicator)
Severity and evolution of
underlying cirrhosis
Child-Pugh score
• Functional reserve of cirrhotic patients
underlying portocaval shunt surgery
• Not entirely appropriate for HCC (resection/
transplantation)
MELD

Staging systems

Staging systems (Tumor spread)
T staging (Liver Cancer Study Group of Japan; LCSGJ)
Size < 2cm > 2cm
Number 1 >1 1 >1
Vascular
Invasion
- + - + - + - +
T1 T2 T2 T3 T2 T3 T3 T4

Tx: Primary can’t be assessed
T0: No evidence of primary tumor
T4: Main branch of portal or hepatic vein (previously T3B)
T4: direct invasion of adjacent organs (except gallbladder) or perforation of visceral
peritoneum
T staging (American Joint Committee on Cancer (AJCC) / International Union Against
Cancer (UICC)) (8th edition; 2017)
Number 1 >1
Size ≤ 2 cm > 2 cm None > 5 cm Any > 5cm
Vascular Invasion - + - +
T1a T1a T1b T2 T2 T3
Previously T1 T2 T1 T2 T2 T3A

Regional Lymph Nodes (N)
Nx Can’t be assessed
N0 No regional LN metastasis
N1 Regional LN metastasis
Distant Metastasis (M)
Mx Can’t be assessed
M0 -
M1 +

Stage T N M
IA 1a 0 0
IB 1b
II 2 0 0
IIIA 3 0 0
IIIB 4
IVA Any 1 0
IVB Any Any 1

Edmondson grade (Histologic Grade (G))
Grade can’t be assessed GX
Well differentiated G1
Moderately differentiated G2
Poorly differentiated G3
Undifferentiated G4

Fibrosis score (F)
F0 Fibrosis score 0-4 (no to moderate fibrosis)
F1 Fibrosis score 5-6 (severe fibrosis or cirrhosis)
Stage 5 year survival rate
F0 F1
I 64% 49%
II 46% 30%
III 17% 9%
AJCC manual recommends notation of fibrosis but hasn’t yet formally incorporated F classification into staging system

Staging systems (Cancer-related symptoms / patient)
Eastern Cooperative Oncology Group (ECOG) Performance status (1982) *
(ak.a. WHO performance status score / Zubrod score)
0 Fully active, able to carry on all pre-disease performance without restriction Asymptomatic
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of light
or sedentary nature .e. light house work or office work
Symptomatic but
completely ambulatory
2 Ambulatory and capable of all self care but unable to carry out any work activities. Up and
about > 50 % of waking hours
Symptomatic , < 50 % in
bed during day
3 Capable of only limited self care, confined to bed/chair > 50 % of waking hours Symptomatic , > 50 % in
bed, but not bed bound
4 Completely disabled. Can’t carry on any self care. Totally confined to bed/chair Bedbound
5 Dead Death
* Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am
J Clin Oncol. 1982;5:649-655.

Staging systems (Cancer-related symptoms / patient)
*Karnofsky D, Burchenal J, The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C, ed.
Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University Press; 1949:191–205

Staging systems (Liver function/damage)

 C(T)P score
 Rough estimate of gross synthetic capacity of liver
 validated as predictor of survival after surgery in cirrhotic liver
 A: major liver resection
 B: Minor liver resection
 C: ‘significant risk from anesthesia and laparotomy
 Only candidate for OLT (orthotopic liver transplantation)

Model for end-stage liver disease (MELD) score
• Objective measure of extent of liver disease, relying only on quantifiable lab values vs subjective physical
findings such as ascites or encephalopathy
• Most helpful in determining allocation for liver transplant

Staging systems
Italy CLIP Cancer of Liver Italian Program 1998
France GRETCH
/French
Groupe d'Etude et de Traitement du Carcinome
Hépatocellulaire
1999
Spain BCLC Barcelona Clinic Liver Cancer 1999
Hong Kong CUPI Chinese University Prognostic Index 2002
HKLC Hong Kong Liver Cancer 2014
Japan Okuda staging 1985
JIS /JSS Japan Integrated Staging (c-JIS, bm-JIS) 2003/2008
Tokyo system
Taiwan TIS Taipei Integrated Scoring System 2010
NATURE scoring system
NIACE (Number, Infiltration, AFP, CP, ECOG) score
MES(IA)H Model for Estimated Survival (in Ambulatory) HCC

Staging systems
Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to
treatment. Study of 850 patients. Cancer 1985;56:918-28.
Stage Median Survival
I 11.5 months
II 3 months
III 0.9 months

Staging systems
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver
Italian Program (CLIP) investigators. Hepatology 1998;28:751-5.
CLIP score Median survival
0 36-42 months
1 22-32 months
2 8-16 months
3 4-7 months
4 - 6 1-3 months

Staging systems
Chevret S, Trinchet JC, Mathieu D, et al. A new prognostic classification for predicting survival in patients with
hepatocellular carcinoma. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. J Hepatol 1999;31:133-41.
Score Range: 0-11

Staging systems
Leung TW, Tang AM, Zee B, et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma
and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program
staging system: a study based on 926 patients. Cancer 2002;94:1760-9.
Scorerange:-7to12

Staging systems
Kudo M, Chung H, Osaki Y. Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and
limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score). J Gastroenterol
2003;38:207-15.

Staging systems (BCLC)

Staging systems (BCLC)
Merits Demerits
Externally validated Not validated in eastern countries
Each stage combined with treatment
algorithm
Advanced stage can be further divided
into 2 groups
• Locally advanced (PV invasion)
• Advanced (extrahepatic metastasis)
Supported by AASLD and EASL

Treatment
 Wide range of treatment options
 Curative (transplantation, resection, ablation)
 Chemoembolization, systemic therapy
 Multidisciplinary team meeting
 Liver surgeon
 Interventional radiologist
 Oncologist
 Hepatologist

Treatment
 In case of underlying liver disease(cirrhosis)
 Only transplantation is curative
 Recurrence constant with all other options

Treatment
 Without cirrhosis (small group)
 Resection: ideal treatment
 With cirrhosis
 Challenging: Patient , liver (FLR) and tumor factors need to
be considered
 HCC identified by surveillance
 Usually smaller; hence curative treatment
 Access to curative treatment ? (22.8 %)

Treatment
 HCC in normal liver (no or minimal coexisting
fibrosis)
 Partial liver resection (treatment of choice)
 Non-tumourous liver has high regenerating capacity
 Perioperative mortality < 1 % ( especially in metabolic
syndrome)
 Perioperative morbidity < 15 %
 5 year survival rate > 50 %
 Lymphadenectomy recommended (15 % risk vs < 5 % in
cirrhotic)

Treatment
fibrosis)
 Adjuvant chemotherapy not recommended
 Regular follow up with CT-chest/abdomen 6 monthly
 Early detection and treatment of recurrence may improve
survival
 Percutaneous ablation
 No role (large size tumor at diagnosis)

Treatment
fibrosis)
 Transplantation
 10 % perioperative mortality
 Long term immunosuppression
 Long term results similar to resection

Treatment
fibrosis)
 Transplantation (indications) (5 year SR: 59 %)
 Primary treatment
 Partial resection preclude by anatomical factors
 Need to preserve sufficient volume of liver remnant
 Rescue treatment
 Intrahepatic tumor recurrence not amenable to repeat
resection

Treatment
 HCC in cirrhotic patients
 Liver resection
 Limitations
 20-60 % multifocal at time of diagnosis (ideally 1)
 Cirrhosis (post operative complications)
 High risk of recurrence (cirrhosis persists)
 Oncological resections (wide margins) vs liver
disease (parenchymal sparing)

Treatment
 Liver resection (risk of surgery)
 Morbidity
 coagulation defects (increased PT ; peak on day 1)
 portal HTN,
 liver failure (raised bilirubin; peak on day 3-5)
 PT/bilirubin normalize in 5-7 days but delayed or absent in cirrhosis)
 impaired regeneration PT< 50 % normal and bilirubin > 50umol/L on day 5;
post operative mortality 50 %)
 Mortality (10 % or more; 1990’s; now decreased to (0%) 4-6 %)
 Patient selection,
 operative technique and
 perioperative management

Treatment
 Liver resection (selection)
 Child-Pugh A
 Without clinically significant portal HTN
 Hepatic venous pressure gradient > 10 mmHg
 Presence of esophageal varices
 Splenomegaly (> 12 cm)
 Thrombocytopenia < 100 000/uL
 Portosystemic shunts (patent umbilical vein)
 Ascites
 Unifocal resectable

Treatment
 Liver resection
 CP - B/C: prohibitive risk of early liver failure even after
minor resection or mere laparotomy
 CP – A: still increased risk of liver failure after major
liver resection (impaired regeneration)
 Correlates with fibrosis grade (F) (F1> F0)
 Additional selection criteria: Indocyanine green
(ICG)

Treatment
 Indocyanine green (ICG; Japan)
 0.5 mg ICG/Kg
 Retention after 15 mins (ICG-R15) in peripheral blood
 Normal 10 %
 Minor resection: 22 % or less
 Major resection: 14-17 %
 USA/Europe
 Absence of significant portal HTN or cytolysis

Treatment
 Liver resection (prognostic factors/indicators)
 Normal bilirubin
 Absence of clinically significant portal HTN
 MELD score
 Thrombocytopenia
 Irrespective of CP grade and tumor features

Treatment
In cirrhotic patients , who have single resectable lesion,
hepatectomy should only be performed if they have well-
preserved liver function, with normal bilirubin and heaptic
venous pressure gradient < 10 mmHg (so called BCLC
stage A)

Treatment
 Optimal management of remnant liver
 More selective use of inflow occlusion
 Avoiding excessive mobilization of liver
 Measuring future remnant liver volume (RLV) using CT
reconstruction. (40 % of total liver volume in CLD required
for major hepatectomy)
 Preoperative PV embolization (PVE)
 Test ability of liver to regenerate
 Ethanol/glue: atrophy of right lobe in 2-6 weeks and
compensatory hypertrophy of left lobe

Treatment
 Liver resection
 PVE +/- ablation: routine before right hepatectomy in
cirrhotic liver
 Parenchymal size vs functional evaluation of remnant
liver volume

Treatment
 Liver resection (Technique)
 Anatomical Resections (remove both the tumor and
adjacent segments that have same portal tributaries) vs
limted resections / tumorectomies
 Wide margins > 1-2 cm to ensure potential satellite
nodules are also resected vs limited margins
 Improves long term survival without increasing
perioperative risk

Treatment
 Rationale: tumor spread via microvascular invasion
 Tumor diameter
 Poor differentiation
 Survival Benefit
 Anatomical: 20 % improved
 Margins: 75 % 5-yr SR (2 cm) vs 49 % (1 cm)

Treatment
 Laparoscopic:
 Less intraoperative bleeding
 Fewer postoperative complications
 Less analgesia, short stay
 Low risk of postoperative ascites
 Facilitates subsequent transplantation (less adhesions)

Treatment
 Liver resection (Outcome)
 5 year SR: 44 % (as high as 68 % CP grade A, well
encapsulated , < 2 cm)
 10 year SR: 29 %
 Factors
 Age, degree of liver damage, AFP level, tumor diameter,
number of nodules, vascular invasion an surgical margins

Treatment
 Liver resection (Treatment of recurrence)
 Major cause of death after resection (persist precursor)
 40 %(1 year), 60 %( 3 years), 80 % (5 years)
 True recurrence (60-70%) vs de novo tumors (30-40%)
 Within 2 years (vascular invasion, poor grade,
satellites, number of nodules)
 > 2 years (main risk factors same as primary HCC)
 Multifocal (50 %), distant metastasis (15 %; lungs,
adrenal, bones) (distant recurrence alone infrequent)

Treatment
 Neoadjuvant/adjuvant treatments not recommended for recurrence
reduction
 Preoperative chemoembolization
 Neoadjuvant/adjuvant chemotherapy
 Internal radiation with 131I-labelled lipiodol (adjuvant; improved
survival till 7th year post operatively; 88 % HBV -HCC)
 Adoptive imnnuotherapy
 Retinoic acid or interferon (low quality studies) or anti angiogenic
therapy (under evaluation)

Treatment
 Most effective to prevent recurrence: Transplantation in
selected patients
 Others:
 Management of underlying cirrhosis/CLD (prognosis
and recurrence)
 Active surveillance post surgery and active treat
recurrences if confined to liver (surgery or
transplantation) (survival benefit ?)

Treatment
 Liver transplantation; LT (rationale)
 Only tumor for which transplant plays significant role
 Most attractive therapy:
 removes detectable and undetectable tumor
 Removes all pre neoplastic nodules
 treats underlying cirrhosis
 Prevent development of postoperative or distant
complications associated with portal HTN and liver
failure

Treatment
 Liver transplantation; LT (selection)
 Limitations
 Availability in most endemic areas of HCC
 Donor shortage
 Only in fraction of HCC cases (< 5 %)
 Potential candidate if survival is around same as those transplanted
for other indications
 Confined to liver (i.e. no extrahepatic disease including LNs)
 Without vascular extension
 Limited tumor burden

Treatment
 Liver transplantation; LT (selection; definition of tumor burden)
 Milan criteria
 Single tumor < 5 cm
 2 or 3 tumors < 3 cm
 5 year SR: 60 %-75 %
 Limitations: Too restrictive (need for expanded criteria)
 UCSF criteria
 Single tumor < 6.5 cm
 3 or fewer, largest < 4.5 cm, sum of diameters < 8 cm
 Others: Poor differentiation, high/increasing AFP
 2012 consensus: limited expansion of standard Milan criteria
 Future: Molecular profiling rather than tumor morphology

Treatment
 Liver transplantation; LT (treatment on waiting list)
 Average time (listing  transplant): > 12 months
 25 % excluded due to disease progression
 3 approaches
 Living-donor transplant (LDT)
 Risks: inherent risk for donor, small-for-size graft (25-30 % have
potential donor)
 Merits: perform rapidly, avoid drop-out on waiting list
 MELD organ allocation policy (2002; USA) priority to HCC within
Milan criteria
 Resection/ablation/chemoembolization during waiting period to
prevent progression beyond criteria.

Treatment
 Trans arterial chemoembolization (TACE)
 Combination of intra arterially infused chemotherapy and hepatic artery
occlusion
 Infused into liver either before embolization or impregnated in gelatin
sponges used for embolisation
 Transcatheter Arterial Embolization (TAE)
 Omits doxorubicin (most common chemotherapeutic agent)

Treatment
 Trans arterial chemoembolization (TACE) (Technique)
 HCC (vs normal liver) receives 100% blood supply from artery
 Obstruction of feeding artery; ischemia; necrosis
 Supra selective embolization: accessory arteries like diaphragmatic or
mammary should also be embolised
 Iodized oil (Lipiodol):
 Improve efficacy, hyperdense on CT , cleared from normal liver,
retained in malignant cells (several weeks-year)
 Used for targeting cytotoxic drugs and increasing their concentration
in tumor (DC-Beads ; drug eluting beads loaded with doxorubicin)
 TACE and antiangiogenic combination (under evaluation)

Treatment
 Trans arterial chemoembolization (TACE) (Contraindications)
 Liver decompensation
 Biliary obstruction
 Bilio-enteric anastomosis
 Impaired kidney function
 PV thrombosis (unless limited to section of liver only and TACE an be
performed in highly selective manner on limited tumor volume)

Treatment
 Trans arterial chemoembolization (TACE) (M&M)
 Mortality < 1 %
 Post-embolization syndrome (> 75 %)
 Fever, abdominal pain, nausea, high ALT/AST
 Not prevented by antibiotics/NSAID
 Self limiting (< 1 week)
 Others (< 5 %): Cholecystitis, GB infarction, gastric or duodenal wall
necrosis, acute pancreatitis (less if supraselective TACE)
 Hepatic abscess (0.3 %), high mortality
 Risk factors: bilioenteric anastomosis, large tumor, PVT

Treatment
 Trans arterial chemoembolization (TACE) (Monitoring)
 CT at 1 month
 Disappearance of arterial vascular supply to tumor
 Decrease in diameter
 Persistent vascularization with decrease size (residual tumor)
 Compact lipiodol uptake without residual vascularization
(complete necrosis without size reduction)

Treatment
 Trans arterial chemoembolization (TACE) (Efficacy)
 Improves survival
 Median survival 34 months
 1- year (82 %), 3 – year (47%), 5-year (26 %) and 7-year
(16 %) survival
 Prognostic factors (decreasing order)
 Degree of liver damage, PV invasion, maximum tumor
size, number of lesions, AFP levels

Treatment
 One of 2 non curative treatment options (besides sorafenib)
that can improve survival (unresectable HCC)
 Recommended as 1st line palliative treatment for
 non-surgical patients with compensated CP A and
 large or multifocal HCC, without PVT or extrahepatic
metastasis (BCLC stage B)

Treatment
 Surgical resection preferred over TACE
 Seuqential TACE and RFA in multiple tumors

Treatment
 Percutaneous locoregional ablative therapy (Technique)
 Damaging agents: ethanol or acetic acid
 Energy sources:
 High temperature: RFA(most effective), microwave
or interstitial laser photocoagulation
 Low temperature: cryoablation
 Non-thermal: irreversible electroporation – high
voltage DC, nanopores in cell membrane, apoptosis

Treatment
 RFA (Technique)
 US or CT guidance
 High frequency AC
 Approach: Percutaneous/laparoscopic/open

Treatment
 RFA (Technique)
 Conversion of electromagnetic (RF) energy into heat via
needle electrode (15-18G) inserted in tumor  ionic
agitation and frictional heat  coagulative necrosis ->
death
 Patient is made into electric circuit by grounding pads
applied to their thighs
 Maintain temperature of 55 -100 degree Celsius
throughout the entire volume for sufficient time

Treatment
 RFA (Technique)
 Impedance monitoring: excessive heating  tissue
charring , increased tissue impedance and less energy
absorption
 1st line ablation technique.
 PEI vs RFA
 Low local recurrence
 Fewer sessions

Treatment
 RFA (Advantages)
 Minimally invasive
 Preserve uninvolved liver parenchyma
 No systemic side effects
 Avoid M&M of major liver surgery

Treatment
 RFA (Drawbacks)
 Size: < 5 cm (smaller size, greater complete local control)
 Number: > 3
 repeated punctures
 Multifocal carcinogenesis vs vascular extension (local therapy
ineffective)
 Isoechoic HCC or tumor in segment 4,7 and 8 or left lateral section
extending beyond spleen (not clearly visible on US)
 Superficial or protruding tumors (no intervening hepatic parenchyma –
intraperitoneal bleed or seedling) (absence of safe path)

Treatment
 RFA (Contraindications)
 Gross ascites (intraperitoneal bleed)
 Uncorrected coagulopathy
 Bilio-enteric anastomosis or endoscopic sphincterotomy (bile bacterial
contamination , risk of abscess formation)
 Proximity to colon, duodenum, stomach, biliary confluence
(injured/perforated by heating)
 Pacemaker(RFA, not microwave)
 Proximity of vascular pedicle (cooling effect) (vs MWA)
 Costly, prolonged (20-90 mins) and painful, under G/A (vs short, very
cheap under light sedation; PEI) (MWA: quick, G/A)

Treatment
 RFA (Complications)
 Mortality < 1%
 Morbidity < 10 %
 Most frequent (no /limited impact): Pleural effusion and segmental
intrahepatic dilation
 Severe complications: abscess formation, perforation of adjacent organs
and intraperitoneal bleed
 Tumor seedling (< 5 %)
 Risk factors: subscapular location, poor grade
 Coagulating needle tract may reduce risk

Treatment
 Percutaneous ablation (Methods and margins)
 Tumor and margin control
 Safety margin (control satellite nodules)
 At least 5mm
 3 cm tumor: ablation 4 cm (thermal > chemical)
 Mutlipolar ablation (several probes around tumor)
 Combining ablation with TACE
 Monitoring: CT/MRI at least 1 month
 RFA: hypervascular rim of fibrotic tissue at periphery on late phase CT/MRI
 Follow up scan : 3 monthly for recurrence

Treatment
 Percutaneous ablation (Indications)
 Unsuitable for resection surgery as per AASLD / EASL
 Neoadjuvant in liver transplant candidates
 Recurrence after liver resection
 Alternate or 1st line in selected cases
 < 2 cm (sustained CR 97 %, 5 yr-SR 68 %)
 Meta analyses still favor surgery to ablation in terms of local control and 3
year SR
 US/Iltaly: trend of ablation with low survival – need for evaluation of
expansion of indications

Treatment
 Conventional systemic chemotherapy
 No rationale for using chemotherapy in unresectable HCC outside
clinical trials.
 Single agent chemotherapy (5-FU, Doxorubicin, Cisplatin, Vinblastine,
etoposide, mitoxantrone): transient 15-20 % response
 Combination chemotherapy: no benefit
 Most active agent: Doxorubicin (overall response 19 %)

Treatment
 Anti-angiogenic targeted therapies
 Sorafenib: tyrosine kinases VEGFR 2 and 3, PDGFRβ.
 Median overall survival - CP A cirrhotic advanced HCC (10.7
months vs 7.9 months) (SHARP trail)
 Median time to tumor progression (24 vs 12 weeks) in advanced
(unresectable or metastatic)

Treatment
 Side effects: Diarrhea (39 %), hand-foot syndrome (21%),
anorexia (14 %), alopecia (14%)
 Safety profile, anti-tumor effect and PK similar for CP A
and B.
 1st line palliative option patients not eligible for resection,
transplantation, ablation or TACE, (Advanced HCC) if
they still have preserved liver function (CP A (or B))
 Others: bevacizumab, sunitinib

Treatment
 Anti-EGFR agents
 Elotinib
 Cetuximab
 Contraindications
 CAD, Cardiac failure, systemic HTN, CP B or C
cirrhosis

Treatment
 Radiotherapy
 External beam radiotherapy: limited role as normal liver is very
radiosensitive
 Safe dose: 30 Gy. Higher dose (Radiation hepatitis and liver failure)
 Indications: Unresectable HCC in hilum or adjacent to main PV or
IVC (local ablation not possible) (avoids subsequent liver failure)
 Modified stereotactic radiation techniques
 Hypofractionation
 High ablative dose to center of tumor
 Controlling for respiratory motion

Treatment
 Radioembolisation
 Radioisotopes (131iodine-iodised oil or 90Yttrium (90Y)-
labelled microspheres directly into hepatic artery
 Less toxicity and increased delivery to tumor
 Iodised oil: comparable efficacy to chemoembolization in
HCC not complicated by PVT and superior if PVT
 25 um spheres lodge at distal arteriolar level, emitted
radiation penetrates 10 mm, delivering dose of 150 Gy

Treatment
 Radioembolisation (vs TACE in BCLC stage A and B)
 90Y: safe and effective and alternate to TACE in PVT
 Prolongs time of progression (> 26 months vs 6.8 months)
 Impact on survival unknown
 Indications
 Not candidate for ablation/transplantation/resection
 Bridge/downstage advanced HCC

Treatment
 High dose, hypofractionated proton beam therapy (Phase II trail)
 Local control for unresectable HCC (CP A or B)
 Other treatments (ineffective)
 Antiandrogenic
 Antiestrogenic
 Somatostatin analogues

Defining a treatment strategy
 Uncomplicated HCC with CLD
 Transplantation (if available, 1st choice)
 Extent of liver disease, age, associated conditions
 > 6 months waiting time: resection/ablation/TACE
 Resection (if transplantation is not available or not indicated)
 Limitation: number (ideally 1), severity (CP A and neither
cytolysis, portal HTN nor impaired ICG test)
 Right hepatectomy: PVE +/- TACE before resection

 RFA
 If no resection due to severity of liver disease and nodule is single (or
less than 3) and size < 5 cm
 1st line treatment for single < 2cm tumor (alternative to resection)
 TACE
 If neither resection nor RFA indicated
 Pre requisite : no ascites or liver failure (bilirubin < 50umol/L) and
tumor burden not too extensive (no vascular invasion or extrahepatic
metastases)

 Anti-angiogenic treatments
 Remaining cases
 Neither liver failure nor vascular disease
 Transplantation (< 5 %)
 Resection (10-15 %)
 Ablation (15-20 %)
 TACE (30-40%)

 Complicated HCC (with macroscopic PV invasion)
 Contraindication for transplantation and ablation
 TACE
 Traditionally contraindicated
 Today occasionally performed if thrombus limited to section of liver
(highly selective embolization with reduced doses and partial arterial
occlusion as endpoint)
 Surgical resection: if main PV not involved
 Otherwise:
 Radio embolization
 Anti angiogenic therapy

 Complicated HCC (with macroscopic hepatic vein invasion)
 Confined to hepatic vein: resection if possible can be proposed
 High risk of pulmonary metastases within 6-12 months post
surgery
 Extension in IVC or right atrium: beyond any treatment

 Complicated HCC (ruptured)
 Actively treated unless terminal presentation (multiple tumors, PVT and
end stage liver disease)
 Primary aim of treatment: Stop bleeding (arterial embolization)
 Subsequent hepatectomy (long term survival)
 Source of bleed:
 Tumor rupture
 Rupture of artery at junction of tumor and adjacent parenchyma
 Rupture not always associated with peritoneal seeding of tumor cells

THANK YOU
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Hepatocellular carcinoma

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