Ed Huang, Senior Talk - He Pa to Cellular Carcinoma (April 2007)

8/9/2019 Ed Huang, Senior Talk - He Pa to Cellular Carcinoma (April 2007)

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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



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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


(AASLD) guidelines for surveillance:

Asian males >40 years old

Asian females >50 years old Family history of HCC

Africans over age 20



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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).


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.


Okada S et al. Gastroenterology 194;106:1618-1624

Poon et al. Ann Surg 2002;235:373-382


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Surgical Resection


(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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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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(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.



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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


(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.



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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


(AASLD) guidelines:

- TACE first line non-curative therapy for non-

surgical patients with no vascular invasion ormetastasis.



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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

Ed Huang, Senior Talk - He Pa to Cellular Carcinoma (April 2007)

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