HEPATOCELLULAR CARCINOMA

Heba Mohamed Fahmy

إخالص النية• 1- ا ل ت خ ف ي ف م ن ا ال م و ا و ج ا ع م ر ض ي ا ل س ر ط ا ن و م ح ا و ل ة إ ي ج ا د ع ال ج ا ت

ت ف ت ح ب ا ب ا أل م ل و ت ك و ن ب أ ق ل أ ع ر ا ض ج ا ن ب ي ة• .... ه ذ ا ا ل ت ع ا و ن م ن ب ا ب ت ع ا و ن و ا ع ل ي ا ل ب ر و ا ل ت ق و ي -2• ... ت ن م ي ة ر و ح ا ل ف ر ي ق ا ل و ا ح د ف ي د ا ل ل ه م ع ا ل ج م ا ع ة -3

• 4- ن ب ذ ا ل خ ال ف ا ت و ا ل م ش ا ك ل ب ي ن ن ا و ل ي ك ن ه د ف ن ا ا ال س م ي أ ن ن ق و ي ب ع ض ن ا ا ل ب ع ض

• م س ا ع د ة ص غ ا ر ا ل ب ا ح ث ي ن و ض م ه م إ ل ي ن ا ب ق د ر ا ل م س ت ط ا ع -5• 6- أل ن ن ا ب ب س ا ط ة س ن ن ج ح م ع ا أ و. . ل ن ي ك و ن ه ن ا ك ك ر ا ه ي ة و ال ح ق د ب ي ن ن ا

ن ف ش ل م ع ا• 7أ ن ن س ل ك ط ر ي ق ا ن ل ت م س ف ي ه ع ل م ا ف ي س ه ل ا ل ل ه ل ن ا ط ر ي ق ا إ ل ي ا ل ج ن ة -

General info.•Hepatocellular carcinoma is the 5th most common malignancy worldwide & the 3rd cause of cancer related death •Most common in males•Incidence depends on geographic distribution •HCC increases with age•HCC increases during last years

CausesHepatitis B

(increases risk 100-200 fold)

Cirrhosis

Toxins(Alcohol, tobacco

& alfactoxins)

Hepatitis C Diabetes mellitus Overweight in males

Autoimmune hepatitis

Signs & symptoms

Nonspecific symptoms• abdominal pain• Fever, chills• anorexia, weight loss• jaundice

Physical findings• abdominal mass in one third• splenomegaly• ascites• abdominal tenderness

Diagnosis

AFP produced by 70% of HCC

• > 400ng/ml• AFP increases

over time

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

Biopsy is rarely required for diagnosis

• Biopsy of potentially operable lesions should be avoided where possible

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

Recurrence rates of 50–60% after 5 years after resection are usual (intrahepatic)Patients with replicating HBV/ HCV had a worse outlook due to recurrence and were previously not considered candidates for transplantation.

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 • Useful for tumor control in patients awaiting liver

transplant

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)

Treatment (non-Surgical)5) Systemic chemotherapy • very limited role in the treatment of HCC with poor

response rate • Best single agent is doxorubicin • 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 adoptive immunotherapy (adjuvant)

Investigational combination therapies in HCC

Combinations under investigations• Bevacizumzb + erlotinib• Sorafenib +erlotinibCombination therapy will likely be used to treat HCC in the future

HCC (What’s ahead?)

•Combinations therapy

• Bevacizumzb or Sorafenib + Erlotinib•Sorafenib + mTOR inhibitor

•Early sequential therapies

De Minicis, S., Kisseleva, T., Francis, H., Baroni, G. S., Benedetti, A., Brenner, D., Alvaro, D., et al. (2012). Liver carcinogenesis: Rodent models of hepatocarcinoma and cholangiocarcinoma. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. doi:10.1016/j.dld.2012.10.008

The paper

Genotoxic

Promoting agents

Carcinogenic agents

The “N-nitrosodiethylamine” model

DEN

acts

in 2

diff

eren

t wa

ys

By alkylating DNA structures , so leas

to DNA damage and cell

degeneration

Inducing ROS through

activation of cytochrome P450

in hepatocytes

DEN model depends on:•1- Dose•2- Timing of administration •3-Sex, age, mice strains.•4- Association with promoting agents

DEN + Phenobarbital (PB)• - Adult male B6C3F1 mice initiated with DEN (6-10 weeks age)

Then PB is added to drink water for 36 weeks (promoting agent)

The peroxisome poliferators model

• -The preroxisome poliferator-activated receptors (PPARs) are nuclear receptors that bind to fatty acid-derived ligands and activate the transcription of genes that regulated lipid metabolism •The formed PPARs ligand activated peroxisomal oxidase and induced ROS thus promoting HCC development.

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