HEPATOMA

Dr Isbandiyah, SpPD

Epidemiology
Hepatocellular carcinoma is the 5th most common
malignancy worldwide & the 3rd cause of cancer related
death with male-to-female ratio
5:1 in Asia
2:1 in the United States

Tumor incidence varies significantly, depending on

geographical location.
HCC

with age.
53 years in Asia
67 years in the United States.

Etiology
Hepatitis B
-increase risk 100 -200 fold
- 90% of HCC are positive for (HBs Ag)

Hepatitis C
Cirrhosis
- 70% of HCC arise on top of cirrhosis

Toxins

-Alcohol

-Tobacco

- Aflatoxins

Autoimmune hepatitis
States of insulin resistance- Overweight in
males Diabetes mellitus

Risk Factor
HBV

Malignant Transformation
Multistep
HCC[2]
Epigenetic
alterations
Genetic
Dysplastic nodules[1]
alterations
Liver cirrhosis
Hepatitis C
Hepatitis B
Ethanol
NASH
Normal liver

Phatology
Microscopically, there are four cytological
types:
fibrolamellar,
pseudoglandular (adenoid),
pleomorphic (giant cell) and
clear cell.

Signs & symptoms

Nonspecific symptoms

abdominal pain
Fever, chills
anorexia, weight loss
jaundice

Physical findings

abdominal mass in one third

splenomegaly
ascites
abdominal tenderness

Diagnosis
what investigations are required to make a
definite diagnosis
1)

2)

AFP produced by 70% of HCC

> 400ng/ml
AFP over time

Imaging
- focal lesion in the liver of a patient with cirrhosis is highly likely
to
be HCC
- Spiral CT of the liver
- MRI with contrast enhancement

Diagnosis

3)

Biopsy is rarely required for

seeding
diagnosis
in 13%.
Biopsy of potentially operable lesions
should be avoided where possible

Diagnostic Procedures
In patients with lesions less than 1
cm, >>>> conservative
management with close follow-up
and no biopsy is recommended.
In patients with 1- to 2-cmlesions,
abiopsy should be performed,.
Patients with lesions greater than 2
cm, cirrhosis, characteristic imaging
studies, and elevated AFP values can
be managed without biopsy.
Patients with large tumors who are
not candidates for resection or
transplantation, >>>>>> biopsy is
frequently not indicated.

Diagnosis
Cirrhosis +
Mass > 2 cm

Raised
AFP

Normal
AFP

Confirmrd
diagnosis

CT, MRI

Diagnosis
Cirrhosis + Mass < 2 cm

Normal AFP

Raised
AFP

CT, MRI
Assess for
surgery

lesion by exam

Confirmed
diagnosis

FNAC or biopsy

AJCC/UICC Classification
System

Child-Pugh score
The Child-Pugh score is used to
assess the prognosis of chronic liver
disease, mainly cirrhosis. To
determine treatment required and
the necessity of liver
transplantation.
The score employs five clinical measures
of liver disease. Each measure is scored
1-3, with 3 indicating most severe
derangement.

Chronic liver disease is classified into

Child-Pugh class A to C, employing
the added score from above.

Management of Hepatocellular
Carcinoma Requires a Multidisciplinary
Approach
Hepatobilia
ry Surgery
Hepatolo
gy

Oncolog
y

Pathology

Radiolog
y
Radiation
Oncology

Treatment/Management

Surgical resection
Liver transplantation
Percutaneous ablation
Alcohol injection
Radiofrequency ablation

Radical

Potentially
Curative

Transarterial embolization and

chemoembolization
Chemotherapy.

Palliative

 Important features that guide

treatment include:

Size
Spread (stage)
Involvement of liver vessels
Presence of a tumor capsule
Presence of extrahepatic
metastases
Vascularity of the tumor

Staging Strategy and Treatment for

Patients With HCC
HCC
PST 0, Child-Pugh A

PST 0-2, Child-Pugh A-B

PST > 2, Child-Pugh C

Very early stage Early stage Intermediate stage Advanced stage

Single < 2 cmSingle or 3 nodules Multinodular, PST 0 Portal invasion,
3 cm, PST 0
N1, M1, PST 12
Single

3 nodules 3 cm

Portal pressure/bilirubin
Increased
Normal
Resection

Terminal
stage

Portal invasion,
N1, M1

Associated
diseases

No
Liver transplant

Yes
PEI/RF

Curative treatments

Llovet JM, et al. J Natl Cancer Inst.

2008;100:698-711.

No
TACE

Yes

Sorafenib
Symptomatic
(unless LT)

Surgery: Resection and Transplantation

Surgery is the mainstay of HCC treatment and

achieve the best outcomes in well-selected
candidates.
Less than 5% patients resectable
Factors affecting resectability:
Size<5cm
number of tumors
involvement of major structures
hepatic function
no extra-hepatic spread
no portal hypertension
Requires experienced surgical and supporting team

5 year survival 60%-70%

3 year recurrence 45 - 60%

Transplantation

Milan Criteria :
Single HCC 5 cm or
Up to three nodules 3 cm
No extra hepatic spread
About 10 % qualify for listing
The major drawback of
transplantation is
The scarcity of donors.
The long waiting time.

Percutaneous Treatments

For patients who cannot undergo

resection.
Complete responses in more than 80% of
tumors smaller than 3 cm in diameter, but
in 50% of tumors of 3-5 cm in size.
5-year survival rates of 40%-60%.
reported in patients with small single
tumors, commonly <2 cm in diameter.
Although these treatments provide good
results, they are unable to achieve
response rates and outcomes comparable
with surgical treatments.
Transarterial Embolization and
Chemoembolization is recommended as
first line non-curative therapy for nonsurgical patients with large/multifocal
HCC who do not have vascular invasion or

Percutaneous Ethanol Injection

patients with cirrhosis + HCC <

5 cm
100% Ethanol
Follow up was 25 months
No complications
4.3 sessions per patient
88% complete necrosis
1 ,2,3-year survival rates:
90,80,63%
Cancer 1992;69:925

Radiofrequency Ablation

Palliative Therapies
Primary treatment for unresectable HCC.
Embolization agents usually gelatin or
microspheres may be administered
together with selective intra-arterial
chemotherapy mixed with lipiodol
(chemoembolization).
Doxorubicin, mitomycin and cisplatin are
the commonly used antitumoral drugs.
Arterial embolization achieves partial
responses in 15-55% of patients, and
significantly delays tumour progression
and vascular invasion.

Transarterial Chemoembolization

Meta-analysis of 7 randomized
controlled trials

2 yr survival: 41% (19-63%)

Treatment response: 35% (16-61%)
Risks:

Infection
Tumor lysis syndrome
Hepatic failure

Llovel J He aloI2003"37:429

Systemic Treatments
A meta-analysis of seven RCTs comparing
tamoxifen vs. conservative management,
comprising 898 patients, showed neither
antitumoral effect nor survival benefit of
tamoxifen. Thus, this treatment is
discouraged in advanced HCC.
Systemic chemotherapy has been tested
in nine RCT. The most active agents in
vitro and in vivo are doxorubicin and
cisplatin. Systemic doxorubicin has been
tested in more than 1000 patients within
clinical trials and provides partial
responses in around 10% of cases, without
any evidence of survival advantages .

Chemotherapy
Palliative not Curative.
Regional (Intra-arterial) better that
systemic.
Resistant to many agents.

hepatoma