Post on 30-May-2018
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Management of
Hepatocellular Carcinoma
Edward Huang
PGY3
April 13, 2007
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Topics
Surveillance
Diagnosis
Treatment
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Surveillance
18,816 patients w/ hepatitis B 6 month AFP and U/S.
Mortality reduced by 37%.
Incidence determine at-risk population. Decision
analysis models show surveillance to be cost-effective incirrhotic patients. 1.5%/year incidence of HCC resulted
in increase of 3 month survival.
Zhang, et al. J Cancer Res Clin Oncol 2004 ;130:417-422
Sarasin, et al. Am J Med 1996;101:422-434)
https://www.aasld.org/
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Surveillance
American Association forThe Study of Liver Diseases
(AASLD) guidelines for cirrhosis:
Hepatitis C
Alco
ho
lic cirrho
sis Genetic hemochromatosis
Primary biliary cirrhosis
No recommendation on alpha-1 antitrypsin deficiency,
non-alcoholic steatohepatitis, autoimmune hepatitis
https://www.aasld.org/
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Hepatitis B carriers
0.2%/year incidence in hepatitis B carriers was cost-
effective.
Epidemiological studies show annual incidence of HCC
in hepatitis B carriers ranging from 0.26% -1%/year. South East Asians has 0.2%/year starting at age 40.
First degree relative with HCC should have earlier
surveillance.
African Americans has higher incidence of HCC atyounger age.
Beasley et al. Hepatology 1982;2(suppl):21S-26S
Yu et al. J Natl Cancer Inst 2000;92:1159-1164
Kew et al. Gastroenterology 1988;94:429-442
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Hepatitis B carriers
American Association forThe Study of Liver Diseases
(AASLD) guidelines for surveillance:
Asian males >40 years old
Asian females >50 years old Family history of HCC
Africans over age 20
https://www.aasld.org/
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Diagnosis
Detection of mass in cirrhotic liver is highly suspicious for
hepatocellular carcinoma.
Diagnostic strategies are dependent on diameter sizes.
>2 cm in diameter, 1-2 cm in diameter and
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Diagnosis (>2 cm diameter)
AFP >200 and radiological evidence (arterial
hypervascularity) suggests HCC and does not require
biopsy.
EASL conference recommend diagnosis of HCC withoutbiopsy if 2 imaging modalities (triphasic CT, MRI) are
characteristic. Positive predictive value is >95%.
Arterial hypervascularity with wash out in early or
delayed venous phase, only 1 imaging modality required.
Atypical appearances on imaging requires biopsy.
Torzilli et al. Hepatology 1999;30:889-893
Levy et al. Ann Surg 2001;234:206-209
Bruix et al. J Hepatol 2001;35:421-430
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Diagnosis (1-2 cm diameter)
High likelihood of HCC. Vascular patterns may have
arterial uptake without venous washout. 25% of
dysplastic nodules exhibit this behavior and remain
stable or regress over time.
EASL recommends biopsy regardless of vascular profile.
AASLD recommends CT and MRI to enhance specificity
of finding.
Biopsy is problematic due to sampling error and
disagreement between dysplasia and well-differentiated
HCC.
Non-conclusive biopsy requires closer monitoring.Bruix, et al. J Hepatol 2001;35:421-430.
Kojiro M. Liver Transpl 2004;10(2 Suppl 1):S3-S8.
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Diagnosis
h
ttps://www.aasld.org/
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Treatment
Level of evidence for therapeutic options are limited to
cohort investigations.
Therapies for high rate of response or potential for cure
include surgical resection, transplantation andpercutaneous ablation
Non-curative therapy that improves survival is
transarterial chemoembolization.
Llovet, et al. Lancet 2003;362:1907-1917
Llovet, et al. Hepatology 2003;37:429-442
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Surgical Resection
Treatment of choice for HCC in non-cirrhotics. 5% of
cases in Western countries and 40% in Asia.
Advances that has increased long term survival are
earlier diagnosis, selection of appropriate surgicalcandidates, technology (IUOS).
CT/MRI has allowed for better evaluation of the tumors.
Normal bilirubin and absence of portal hypertension as
measured by hepatic vein catheterization (70% 5 year
survival).
Llovet, et al. Hepatology 1999;30:1434-1440
Bruix et al. Gastroenterology 1996;111:1018-1022
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Recurrence
After resection, tumor recurrence exceeds 70% at 5
years
Predictors of recurrence are presence of microvascular
invasion and additional tumor sites Preoperative or adjuvant chemotherapy are not
effective..
Most patients with recurrence have multifocal disease
from dissemination from primary tumor.
Llovet, et al. Hepatology 1999;30:1434-1440
Okada S et al. Gastroenterology 194;106:1618-1624
Poon et al. Ann Surg 2002;235:373-382
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Surgical Resection
American Association forThe Study of Liver Diseases
(AASLD) guidelines:
Patients with single lesion should be offered surgical
resectio
n if they are non-cirrh
otic
or have cirrh
osiswith preserved liver function, normal bilirubin and
hepatic vein gradient (
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LiverTransplantation
Patients with HCC were part of the initial experiences
with liver transplantation.
Transplantation for solitary tumors
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LiverTransplantation
MELD established in 2002 due to high concordance to
predict mortality for chronic liver disease.
MELD is less powerful in predicting mortality for HCC.
22 points given for patients meeting solitary nodules 2-5cm or 3 nodules each 6 months.
Score = (0.957 loge[Cr]+0.378 loge[Tbili]+1.12 loge[INR]+ 0.643) x 10
Freeman, et al. Liver Tranpl 2002;8:851-858
Freeman, et al. Liver Transpl 2004:10:7-15
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LiverTransplantation
American Association forThe Study of Liver Diseases
(AASLD) guidelines:
- Liver transplantation is effective for patients meeting
the Milan criteria- Preoperative therapy can be considered if waiting time
is longer than 6 months.
https://www.aasld.org/
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Percutaneous Ablation
Treatment option for patients with early stage HCC who
are not resection or transplant candidates.
Destruction is achieved using chemical substances
(ethanol, acetic acid)
or m
odifying temperature(radiofrequency, laser, cryotherapy).
Ethanol is best studied. It achieves necrosis rate of 90-
100%
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Percutaneous Ablation
American Association forThe Study of Liver Diseases
(AASLD) guidelines:
- Local ablation can be used for patients who cannot
undergo resection or as a bridge to transplantation- Alcohol injection and radiofrequency are effective for
tumors 2cm.
https://www.aasld.org/
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TACE (transarterial chemoembolization)
Early HCC recieves its blood supply mainly from portal
vein. As tumor grows, blood supply becomes more
arterialized.
Rationale f
or emb
olizati
on (
T AE). Pri
or to
embolizati
on,chemotherapy agents (adriamycin, cisplatin) are injected
using lipiodol as suspension (TACE). Side effect is post-
embolization syndrome where hepatic artery.
Both TAE and TACE have >50% of patients achieving
tumor necrosis.
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TACE
American Association forThe Study of Liver Diseases
(AASLD) guidelines:
- TACE first line non-curative therapy for non-
surgical patients with no vascular invasion ormetastasis.
https://www.aasld.org/
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Treatment
Early HCC are optimal candidates for resection, liver
transplantation or percutaneous ablation.
Resection is limited to patients a single tumor, usually 6 months, then resection or
percutaneous treatments are recommended prior to
OLT.
Percutaneous ablation is indicated in non-surgical
patients.
Transarterial chemoembolization is indicated for patients
with multinodular tumors that has not metastasize.
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Summary
Surveillance AFP and U/S every 6 to 12 months
targeted at risk patients (cirrhotics, hepatitis B carriers)
Diagnosis Biopsy not necessary unless imaging is
equivocal f
or lesi
ons >1 cm.
Treatment resection, liver transplantation,
percutaneous ablation and transarterial
chemoembolization