Upload
winson-chitra
View
223
Download
0
Embed Size (px)
Citation preview
7/29/2019 Hepatocellular CA(Nop 2010)
1/24
HEPATOCELLULAR
CARCINOMA
Dairion Gatot, Soegiarto Gani, Savita Handayani
Division of Medical Oncology and HematologyDepartment of Internal Medicine
Medan-Kepala Batas 2010
7/29/2019 Hepatocellular CA(Nop 2010)
2/24
Definition
Primary Hepatocellular Carcinoma is
primary liver tumor usually developed in
chronic liver disease especially viral
hepatitis
7/29/2019 Hepatocellular CA(Nop 2010)
3/24
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.
7/29/2019 Hepatocellular CA(Nop 2010)
4/24
7/29/2019 Hepatocellular CA(Nop 2010)
5/24
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.
7/29/2019 Hepatocellular CA(Nop 2010)
6/24
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.
7/29/2019 Hepatocellular CA(Nop 2010)
7/24
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.
7/29/2019 Hepatocellular CA(Nop 2010)
8/24
Contaminated drinking water
China: drinking water from ponds
contaminated by blue-green algal toxin
Microcystin.
7/29/2019 Hepatocellular CA(Nop 2010)
9/24
7/29/2019 Hepatocellular CA(Nop 2010)
10/24
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.
7/29/2019 Hepatocellular CA(Nop 2010)
11/24
Pathogenesis
Methylation disorders (hypo- or
hypermethylation also occurs in CpG
7/29/2019 Hepatocellular CA(Nop 2010)
12/24
7/29/2019 Hepatocellular CA(Nop 2010)
13/24
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
7/29/2019 Hepatocellular CA(Nop 2010)
14/24
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])
7/29/2019 Hepatocellular CA(Nop 2010)
15/24
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
7/29/2019 Hepatocellular CA(Nop 2010)
16/24
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
7/29/2019 Hepatocellular CA(Nop 2010)
17/24
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%.
7/29/2019 Hepatocellular CA(Nop 2010)
18/24
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.
7/29/2019 Hepatocellular CA(Nop 2010)
19/24
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.
7/29/2019 Hepatocellular CA(Nop 2010)
20/24
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)
7/29/2019 Hepatocellular CA(Nop 2010)
21/24
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
7/29/2019 Hepatocellular CA(Nop 2010)
22/24
Targeted Therapy
Sorafenib = multitargeted tyrosine kinase
inhibitor.
SHARP trial sorafenib monotherapy as
standard monotherapy for advanced HCC.
7/29/2019 Hepatocellular CA(Nop 2010)
23/24
7/29/2019 Hepatocellular CA(Nop 2010)
24/24