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Epidemiologi
Klasifikasi
Etiologi& Faktor Risiko
Manifestasi Klinis
Diagnosis
Sistem staging
Terapi
An estimated 22,620 people diagnosed in the United
States in 2009; more common in other parts of the
world
Sixth most frequent cause of cancer-related death
among men and the ninth most common among
women
A disease in which normal liver cells grow
uncontrollably and form a tumor or tentacle-like
growth
Primary liver cancer is cancer that begins in the liver
Three types of primary liver cancer: hepatocellular
carcinoma (HCC), cholangiocarcinoma (bile duct
cancer), and angiosarcoma
HCC accounts for 90% of primary liver cancer cases
6th most common cancer world wide
• (626,000 or 5.7% of new cancer cases)
Third most common cause of cancer mortality
• Deaths = 598,000
Survival rates 3% - 5% for the US and
developing countries
Fastest growing cause of cancer-related death in
men in the US
• 19,160 cases and 16,780 deaths
Parkin, D.M., et al., Global cancer statistics, 2002. CA Cancer J Clin, 2005. 55(2): p. 74-108.
#6
Estimated Numbers
of New Cancer
Cases and Deaths in
2002
• 6% 5 yr survival rate
#7
El-Serag, H.B. and A.C. Mason, Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med, 1999. 340(10): p. 745-50.
JINAK GANAS
Tumor Epitelial
Adenoma hepatoselular Karsinoma hepatoselular
Adenoma bilier intrahepatik Karsinoma fibrolamelar
Sistadenoma bilier intrahepatik Hepatoblastoma
Papilomatosis bilier Kolangiokarsinoma
Sistadenokarsinoma
Tumor Mesenkimal
Hemangioma Angiosarkoma
Fibroma Fibrosarkoma
Leiomioma Leiomiosarkoma
Lipoma Liposarkoma
Angiomiolipoma Rabdomiosarkoma
Limfangioma Limfoma hepatik primer
Mesotelioma Hemangioendotelioma-
epitelioid
Virus hepatitis B
Virus hepatitis C
Faktor-faktor risiko:
Sirosis hati, pada 60-80% SH makronodular dan 3-10% SH
mikronodular
Aflatoksin
Obesitas
Diabetes melitus hiperinsulinemia dan peningkatan insulin-
like growth factors.
Alkohol
Penyakit hati autoimun
Penyakit hati metabolik (hemokromatosis, defisiensi alfa-1-
antitripsin, penyakit Wilson)
Kontrasepsi oral
Senyawa kimia (vinyl chloride, thorotrast, nitrosamin,
insektisida organoklorin, asam tanik)
Tembakau (masih kontroversi)
HBV
• 5-15 fold increased risk
• 70-90% of cases occur in setting of
cirrhosis
• Treatment does NOT decrease risk
• Risk highest in carriers and lower in
immune
HCV
• 1-3% of cirrhotic patients develop
HCC
• Treatment seems to decrease risk
Co-infection
Aflatoxins (Aspergillus fumigatus)
• 4 fold increased risk HCC
Alcohol
• >50-70g/day
• No link to direct carcinogenic effect
• Synergistic with HCV and HBV
Nonalcoholic Steatohepatitis?
El-Serag, H.B. and K.L. Rudolph, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 2007. 132(7): p. 2557-76.
Brunetto M.R., O.F., Koehler M., et al., Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study.
International Interferon-alpha Hepatocellular Carcinoma Study Group. Lancet, 1998. 351(9115): p. 1535-9.
Obesity
Diabetes Mellitus
Hemochromatosis
Alpha-1 antitrypsin deficiency
Autoimmune hepatitis
Porphyrias
15-50% of HCC in the US have no
established risk factors
Gejala yang paling sering dikeluhkan:
Nyeri atau perasaan tak nyaman di kuadran kanan-atas
abdomen, malaise, penurunan berat badan dan ikterus.
Keluhan gastrointestinal lain adalah anoreksia,
kembung, konstipasi atau diare.
Sesak nafas sebagai akibat besarnya tumor yang
menekan diafragma atau karena metastasis di paru.
Tanda-tanda klinis: Hepatomegali dengan atau tanpa
bruit hepatik, splenomegali, asites, ikterus, demam dan
atrofi otot.
Perdarahan varises esofagus, peritonitis bakterialis
spontan.
Tanda-tanda sindroma neuropsikiatrik/mental confusion
akibat kerusakan hebat sel-sel hati (ensefalopati
hepaticum)
Alfa-fetoprotein: Protein serum normal yang
disintesis oleh sel hati fetal, sel yolk-sac dan
sedikit sekali oleh saluran gastrointestinal fetal.
Nilai diagnostik atau sugestif untuk HCC bila
kadar AFP > 400 ng/mL.
DCP (des-gamma carboxy prothrombin) atau
PIVKA-2, pada HCC kadarnya akan meningkat.
AFP-L3 (suatu subfraksi AFP), memiliki angka
sensitifitas dan spesifisitas paling baik untuk
HCC.
Ultrasonografi, memiliki sensitivitas 70-80%.
Pada HCC yang kecil tampak gambaran
mosaik, formasi septum, bagian perifer
sonolusen (ber’halo’), bayangan lateral yang
dibentuk oleh pseudokapsul fibrotik, serta
penyangatan eko posterior.
USG color Doppler sangat berguna untuk
membedakan HCC dari tumor hepatik lain.
CT-scan, MRI serta angiografi kadang-kadang
diperlukan.
Laparoskopik biopsi Histopathology
“Hepatocellular carcinoma with cholangiolar features, moderately differentiated”
Numerous
staging systems exist and NO
CONSCENSUS
• E.g. TNM, Okuda, CLIP, and BCLC
Incorporate 4 determinants of survival
• Severity of underlying liver disease
• Size of tumor
• Extension of the tumor into adjacent structures
• Presence of metastases
Primary staging should be clinical staging, and
the CLIP is preferred
Secondary staging with the AJCC - TNM staging
system for patients undergoing surgery
Staging work up includes Bone Scan and CT
chest
Child – Pugh Stage Score
A 0
B 1
C 2 Score Average survival
Tumor Morphology 0 31 Mon.
Uninodular , <50% 0 1 27 Mon.
Multinodular, <50% 1 2 13 Mon.
Massive, >50% 2 3 8 Mon.
AFP <400 0 > 4 2 Mon.
>400 1
Portal Vein Thrombosis No 0
yes 1
1 2 3
Bilirubin <2 2-3 >3
Albumin >3.5 3.5-2.8 <2.8
INR <1.7 1.7-2.3 >2.3
Ascites Absent Mild-Moderate Severe / Refractory
Encephalopathy Absent Mild (I-II) Severe (III-IV)
T definitions
• T1 – solitary nodule without vascular invasion
• T2 – solitary tumor with vascular invasion or multiple nodules
all <5cm
• T3 – multinodular >5cm, or tumor with major vasculature
invasion
• T4 – Tumor with invasion of adjacent organs
AJCC Cancer Staging Manual, Sixth Edition (2002) published by Springer-Verlag New York, Inc
Criteria Positive Negative
Tumor size >50% <50%
Ascites Clinically detectable Abscent
Albumin <3 >3
Bilirubin >3 <3
Chang, M.H., et al., Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children.
Taiwan Childhood Hepatoma Study Group. N Engl J Med, 1997. 336(26): p. 1855-9.
Liver
transplantation / Resection (<5% of
cases)
• 5 yr survival 41-93%
Radiofrequency ablation (RFA) (20-30% of
cases)
• 5 yr survival 33-40%
• Solitary tumors, max 3-5cm
Percutaneous ethanol or acetic acid ablation
• 5 yr survival 29-71%
• Solitary tumors, max 3-5cm
Transarterial chemoembolization (TACE)
• 2 yr survival 24-63%
• No vascular invasion, preserved liver function,
no extrahepatic spread
Radiation therapy
Systemic chemotherapy
>100 trials over the last 30 years
Transarterial chemoembolization (TACE)
• 2 yr survival 24-63%
• No vascular invasion, preserved liver function,
no extrahepatic spread
Radiation therapy
Systemic chemotherapy
>100 trials over the last 30 years
Llovt et al. Lancet 362(9399), 6 December 2003, Pages 1907-1917
Reseksi hepatik: untuk pasien dalam kelompok non-
sirosis (klasifikasi Child Pugh A) dan fungsi hati normal.
Reseksi juga pada kelompok HCC lokalisata (kelainan
pada satu lobus hati/(Selected T1 and T2; N0; M0) ),
bagian hati yang direseksi termasuk bagian normal hati ±
1cm.
Transplantasi hati: untuk pasien HCC dan sirosis hati.
Pada pasien HCC lokalisata yang parah/advance
(Selected T1, T2, T3, and T4; N0; M0), bila tidak
dilakukan reseksi Ablasi tumor perkutan: Injeksi etanol
perkutan; Radiofrequency ablation; Polyprenoic acid.
Terapi paliatif: Transarterial embolization/chemo
embolization khususnya pada HCC difus dua lobus atau
belum ada metastase ekstrahepatik. Bila ada metastase
ekstrahepatik, angka mortalitasnya tinggi. (Any T, N1 or
M1)
HCC has been considered to be a relatively
chemotherapy refractory tumor
Survival is often determined by degree of
hepatic dysfunction
Systemic chemotherapy not well tolerated
by patients with significant underlying
hepatic dysfunction
Systemic chemotherapy is injected into a vein and travels
through the bloodstream to the whole body
Regional chemotherapy uses a small pump surgically placed in
the body to deliver anticancer drugs directly to the blood
vessels that feed the tumor
Hepatic arterial infusion is chemotherapy injected into a
catheter in the major artery supplying blood to the liver
Chemoembolization is similar to hepatic arterial infusion except
the flow of blood through the artery is blocked for a short time,
so the anticancer drug stays in the tumor longer; the blocking of
the blood supply to the tumor also kills the cancer cells
Targetsfaulty genes or proteins that contribute to
cancer growth and development