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CARCINOMA
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
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
Autoimmune hepatitis
- Aflatoxins
Incidence according to
etiology
Abbreviations: WD, Wilsons disease; PBC, primary biliary cirrhosis, HH, hereditary
hemochromatosis; HBV, hepatitis B virus infection; HCV, hepatitis C virus infection.
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.
Nonspecific symptoms
abdominal pain
Fever, chills
anorexia, weight loss
jaundice
Physical findings
Guidlines
(a) which patients are at high risk for
the development of HCC and should
be offered surveillance
(b) what investigations are required to
make a definite
diagnosis
(c) which treatment modality is most
appropriate in a given clinical context.
Guidlines
(a) which patients are at high risk for the development of HCC &
should be offered surveillance
Diagnosis
(b) what investigations are required to make a
definite diagnosis
1)
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)
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
FNAB or biopsy
AJCC/UICC Classification
System
Treatment (Surgery)
Treatment (Surgery)
Hepatic resection should be considered in HCC and a noncirrhotic liver (including fibrolamellar variant)
Treatment (Surgery)
Treatment (non-Surgical)
should only be used where surgical
therapy is not possible.
1) Percutaneous ethanol injection (PEI)
Treatment (non-Surgical)
3) Cryotherapy
4) Chemoembolisation
Treatment (non-Surgical)
5) Systemic chemotherapy
very limited role in the treatment of HCC with poor
esponse rate
Best single agent is doxorubicin (RR: 10- 20%)
Combination chemotherapy didnt
response
but
survival
should only be offered in the context of clinical
trials
6) Hormonal therapy
- Nolvadex, stilbestrol and flutamide
7) Interferon-alfa
8) retinoids and adaptive immunotherapy (adjuvant)
Target
Gefitinib
Erlotinib
Lapatanib
Cetuximab
Bevacizumab
Sorafenib (Nexavar)
Sunitinib
Vatalanib
Cediranib
Rapamycin
Everolimus
Bortezomib (Velcade)
EGFR
EGFR
EGFR
EGFR
VEGF
Raf1, B-Raf, VEGFR , PDGFR
PDGFR, VEGFR, c-KIT, FLT-3
VEGFR, PDGFR, c-KIT
VEGFR
mTOR (mammalian target of rapamycin)
mTOR
Proteasome
Investigational combination
therapies in HCC
Combinations under investigations
Bevacizumzb + erlotinib
Sorafenib +erlotinib
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
No
TACE
Yes
Sorafenib
Symptomatic
(unless LT)