Hepatocellular Carcinoma

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HEPATOCELLULAR CARCINOMA

Transcript of Hepatocellular Carcinoma

Page 1: Hepatocellular Carcinoma

HEPATOCELLULAR CARCINOMA

Page 2: Hepatocellular Carcinoma

EpidemiologyHepatocellular carcinoma adalah kelainan malignan sel terbesar ke 5 di dunia & dan ke 3 terbesar kanker yang dapat menyebabkan kematian

– 5:1 di Asia

Variasi terjadinya tumor sangat berbeda tergantung dari lokasi geografi

HCC terhadap umur– 53 tahun di Asia– 67 tahun di Amerika

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Incidence of HCC

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Etiology

• Hepatitis B- Meningkatkan resiko 100 sampai 200 kali

- 90% dari HBs Ag reactive akan mengalami HCC

• Hepatitis C• Cirrhosis

- 70% HCC terjadi setelah sirosis• Toxins -Alcohol -rokok - Aflatoxins

• Autoimmune hepatitis• Penderita diabetes yang insulin resistance- laki-laki

Overweight pada penderita Diabetes mellitus

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Incidence according to etiology

Abbreviations: WD, Wilson′s disease; PBC, primary biliary cirrhosis, HH, hereditary hemochromatosis; HBV, hepatitis B virus infection; HCV, hepatitis C virus infection.

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Signs & symptoms

Nonspecific symptoms– Nyeri perut– Demam, menggigil– malas makan, penurunan berat badan– ikterus

Physical findings– adanya massa di salah satu regio abdomen– splenomegaly– ascites– rasa kembung/penuh pada perut

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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.

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Guidlines

- M &F with established cirrhosis due to HBV and/ or HCV, particularly those with ongoing viral replication

- M &F with established cirrhosis due to genetic haemochromatosis

- M with alcohol related cirrhosis who are abstinent from alcohol or likely to comply with treatment

- M with primary biliary cirrhosis

Abdominal US and AFP/ 6 months

(a) which patients are at high risk for the development of HCC & should be offered surveillance

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Diagnosis

(b) what investigations are required to make a definite diagnosis

1) AFP produced by 70% of HCC> 400ng/ml AFP over time

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

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Diagnosis

3) Biopsy is rarely required for diagnosis

in 1–3%.

Biopsy of potentially operable lesions should be avoided where possible

seeding

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DiagnosisCirrhosis +

Mass > 2 cm

Raised AFP

Normal AFP

Confirmrd diagnosis

CT, MRI

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DiagnosisCirrhosis + Mass < 2 cm

Raised AFP

Normal AFP

Assess for surgery

CT, MRI

lesion by exam

FNAC or biopsyConfirmed diagnosis

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Treatment (Surgery)

The only proven potentially curative therapy for HCC Hepatic resection or liver transplantation

Patients with single small HCC (≤5 cm) or up to three lesions ≤3 cm

Involvement of large vessels (portal vein, Inferior vena cava) doesnt automatically mitigate against a resection; especially in fibrolamellar histology

No randomised controlled trials comparing the outcome of surgical resection and liver transplantation for HCC.

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Treatment (Surgery)

Hepatic resection should be considered in HCC and a non-cirrhotic liver (including fibrolamellar variant)

Resection can be carried out in highly selected patients with cirrhosis and well preserved hepatic function (Child-Pugh A) who are unsuitable for liver transplantation. It carries a high risk of postoperative decompensation.

Perioperative mortality in experienced centres remains between 6% and 20% depending on the extent of the resection and the severity of preoperative liver impairment.

The majority of early mortality is due to liver failure.

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Treatment (Surgery) Recurrence rates of 50–60% after 5 years after resection are

usual (intrahepatic)

Liver transplantation should be considered in any patient with cirrhosis

Patients with replicating HBV/ HCV had a worse outlook due to recurrence and were previously not considered candidates for transplantation.

Effective antiviral therapy is now available and patients with small HCC, should be assessed for transplantation

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Treatment (non-Surgical)should only be used where surgical therapy is not

possible.

1) Percutaneous ethanol injection (PEI) • has been shown to produce necrosis of small HCC. • It is best suited to peripheral lesions, less than 3 cm in

diameter

2) Radiofrequency ablation (RFA)• High frequency ultrasound to generate heat• good alternative ablative therapy • No survival advantage• Useful for tumor control in patients awaiting liver transplant

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Treatment (non-Surgical)

3) Cryotherapy• intraoperatively to ablate small solitary tumors outside a

planned resection in patients with bilobar disease

4) Chemoembolisation • Concurrent administration of hepatic arterial chemotherapy

(doxirubicin) with embolization of hepatic artery• Produce tumour necrosis in 50% of patients• Effective therapy for pain or bleeding from HCC• Affect survival in highly selected patients with good liver

reserve• Complications: (pain, fever and hepatic decompensation)

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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 didn’t response but

survival– should only be offered in the context of clinical trials

6) Hormonal therapy- Nolvadex, stilbestrol and flutamide

7) Interferon-alfa8) retinoids and adaptive immunotherapy (adjuvant)

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Targeted therapy for HCC

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Selection of agents for targeted therapy in HCC

Name TargetGefitinibErlotinibLapatanibCetuximabBevacizumabSorafenib (Nexavar) Sunitinib VatalanibCediranibRapamycinEverolimusBortezomib (Velcade)

EGFREGFREGFREGFRVEGFRaf1, B-Raf, VEGFR , PDGFRPDGFR, VEGFR, c-KIT, FLT-3VEGFR, PDGFR, c-KITVEGFRmTOR (mammalian target of rapamycin)

mTORProteasome

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Targeting angiogenesis for HCC

HCC is one of the most vascular tumor

Major driver of angiogenesis is vascular endothelial growth

factor (VEGF)

Sorafenib and bevacezumab target VEGF in HCC

• Bevacizumzb: Median OS of approximately 12 months

• Bevacizumab + erlotinib: Medain OS 15-17 months

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Investigational combination therapies in HCC

Combinations under investigations– Bevacizumzb + erlotinib– Sorafenib +erlotinib

Combination therapy will likely be used to treat

HCC in the future

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HCC (Whats ahead?)

Combinations therapy

• Bevacizumzb or Sorafenib + Erlotinib• Sorafenib + mTOR inhibitor

Early sequential therapies

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