hepatocellular ca(nop 2010)

7/29/2019 Hepatocellular CA(Nop 2010)

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HEPATOCELLULAR

CARCINOMA

Dairion Gatot, Soegiarto Gani, Savita Handayani

Division of Medical Oncology and HematologyDepartment of Internal Medicine

Medan-Kepala Batas 2010


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Definition

Primary Hepatocellular Carcinoma is

primary liver tumor usually developed in

chronic liver disease especially viral

hepatitis


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Incidence

Liver cancer the fourth cause of death

due to cancer worldwide and the third in

men.

Incidence differs geographically.

Indonesia : one of the countries in which

the incidence of Hepatitis B is

intermediate.


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Hepatitis B dan HCC

Taiwan: HBsAg (+) HCC risk 223 x compared

with HBsAg (-).

Canada & Austria: Risk for Asian population > non

Asia. HBeAg (+) increase HCC risk (RR 60,2 dgn 95% CI

35.5-102.1), compared with only HBsAg (+) (RR

9.6 with 95% CI 6.0-15.2).

HBV DNA load goes in line with HCC risk.

HCV co-infection increases HCC risk.


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Hepatitis C and HCC

Carcinogenesis mechanism of HCV hasnot been clear yet, its suspected that HCV rapid cell turnover and chronic

inflammatory state. USA: one third of HCC cases have a

correlation with HCV.

HCC almost always occurs in livercirrhosis or chronic HCV with high gradeliver fibrosis, meanwhile HCC in chronicHepatitis B can manifests in all condition.


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Aflatoxin

A mycotoxin that commonly contaminates

corns, soya beans,and peanuts. High

aflatoxin diet is associated with HCC

development. Tempe (fermentedsoybeans)?

Aflatoxin mutation in codon 249 tumor

supressor gene p53.

Carcinogenic potentiation with HBV

infection.


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Contaminated drinking water

China: drinking water from ponds

contaminated by blue-green algal toxin

Microcystin.


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Pathogenesis

Hepatocarcinogenesis can take a period of30 years after HBV / HCV infection.

Cytokines from inflammatory cells, cell

regeneration process and viraltransactivation increase ofTransforming Growth Factor (TGF)expression and Insulin Growth Factor-2(IGF-2) through epigenetic mechanismincrease the hepatocyte proliferation.


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Pathogenesis

Methylation disorders (hypo- or

hypermethylation also occurs in CpG


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Paraneoplastic syndrome in HCC

Hipoglicaemia: due to high grade metabolism

IGF-2 increase.

Erythrocytosis: 23% HCCEPO

Hypercalcemia: metastatic bones or PTHrp

secretion.

Diarrhea: due to vasoactive intestinalpolypeptide secretion, gastrin, and peptide

with prostaglandin-like immunoreactivity


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Diagnosis

USG CTscan

MRI

AFP

If the lession is hypervascular, with increase of T2signal intensity in MRI, vein invasion, or accompanied with

AFP increase.

HCC diagnosis

Percutaneous biopsy is only performed if thediagnosis is unclear

Des-gamma-carboxy prothrombin (prothrombin

produced by vitamin K absence or antagonism II

[PIVKA II])


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TNM stagingPrimary tumor (T)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor T1 Solitary tumor without vascular invasion

T2 Solitary tumor with vascular invasion, or multiple tumors none more than 5 cm

T3 Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s)

T4 Tumors with direct invasion of adjacent organs other than the gallbladder or with perforation of thevisceral peritoneum

Regional lymph nodes (N)

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis N1 Regional lymph node metastasis

Distant metastasis (M)

MX Distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis

Fibrosis score (F)*

F0 Fibrosis score 0-4 (none to moderate fibrosis) F1 Fibrosis score 5-6 (severe fibrosis or cirrhosis)

Stage grouping

Stage I T1 N0 M0

Stage II T2 N0 M0

Stage IIIA T3 N0 M0

Stage IIIB T4 N0 M0

Stage IIIC Any T N1 M0

Stage IV Any T Any N M1


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Management

Median survival 6-20 months.

Surgery resection, but majority can not be performed

Treatment of choice:

Liver transplantation Radiofrequency ablation (RFA)

Percutaneous ethanol or acetic acid ablation

Transarterial chemoembolization (TACE)

Cryoablation Radiation therapy

Systemic chemotherapy


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Partial hepatectomy

Potentially curative.

Ideal resection: solitary HCC without

radiological proof showing invasion of liver

vascularisation, no hypertension with good

liver function reserve.

Long-term relapse-free survival 40%, and

five-year survival 90%.


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Radio Frequency Ablation

RFA = localized thermal energy

application from radiopfrequency wave

throuigh electrodes increase of local

lession temperature > 60C necrosis.

It had better performed in single tumor < 4

cm in diameter and with Child-Pugh A or

B.


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Trans Arterial Chemo Embolization

(TACE)

Majority of HCC supply vessels areoriginated from hepatic vein.

Insertion with syringe to hepatic vein : a

chemotherapeutic agent with or lipiodolprocoagulant agent. Lipiodol is a contrastagent that increase intratumoralchemotherapy retention.

Contraindication :portal veinthrombosis,encephalopathy, biliary ductobstruction.


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Radiotheraphy

HCC is a radiosensitive tumor but liver is a

very radiosensitive organ, that can only

receive approximately 20 Gy

stereotactic body radiation therapy(targeted) or selective internal RT with

iodine-131 [131I]- labeled lipiodol or

yttrium-90 [90Y]-tagged glassmicrospheres)


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HCC is regarded as a relatively chemo

refractory. Because of the high expression of

drug resistance gene such as p-glycoprotein,

glutathione-S-transferase, heat shockproteins and p53 mutation.

Chemotherapy


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Targeted Therapy

Sorafenib = multitargeted tyrosine kinase

inhibitor.

SHARP trial sorafenib monotherapy as

standard monotherapy for advanced HCC.


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hepatocellular ca(nop 2010)

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