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
HCV
Sirosis Hati
Aflaktosin B1
Obesitas
DM
Alkoholisme
 Malignant Transformation
Multistep
HCC[2]

Epigenetic alterations
Genetic alterations
Dysplastic nodules[1]

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) AFP produced by 70% of HCC

> 400ng/ml
AFP over time

2) 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 diagnosis

seeding
in 1–3%.
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-cm lesions, a biopsy
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

Raised AFP Normal AFP

CT, MRI

Assess for surgery

lesion by exam

Confirmed FNAC or biopsy

diagnosis
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

Hepatobiliary
Surgery

Hepatology Oncology

Pathology Radiology

Radiation
Oncology
 Treatment/Management

• Surgical resection “Radical”

• Liver transplantation
• Percutaneous ablation “Potentially
– Alcohol injection Curative”

– Radiofrequency ablation
• Transarterial embolization and chemoembolization
“ Palliative ”
• Chemotherapy.
• 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 Terminal
Single < 2 cm Single or 3 nodules Multinodular, PST 0 Portal invasion, stage
≤ 3 cm, PST 0 N1, M1, PST 1-2

Single 3 nodules ≤ 3 cm

Portal pressure/bilirubin Portal invasion,

Associated N1, M1
Increased
diseases

Normal No Yes No Yes

Resection Liver transplant PEI/RF TACE Sorafenib

Curative treatments Symptomatic
(unless LT)
Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.
Bruix J, et al. Hepatology. 2005;42:1208-1236.
 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 non-surgical patients with large/multifocal HCC
who do not have vascular invasion or extrahepatic
spread.
 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