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HEPATOCELLULAR CARCINOMA
Heba Mohamed Fahmy
إخالص النية• التخفيف من االم و اوجاع مرضي السرطان و محاولة إيجاد عالجات -1
تفتح باب األمل و تكون بأقل أعراض جانبية• .... هذا التعاون من باب تعاونوا علي البر و التقوي -2• ... تنمية روح الفريق الواحد فيد الله مع الجماعة -3
• نبذ الخالفات و المشاكل بيننا و ليكن هدفنا االسمي أن نقوي بعضنا -4 البعض
• مساعدة صغار الباحثين و ضمهم إلينا بقدر المستطاع -5• لن يكون هناك كراهية و ال حقد بيننا ..ألننا ببساطة سننجح معا أو -6
نفشل معا• 7أن نسلك طريقا نلتمس فيه علما فيسهل الله لنا طريقا إلي الجنة -
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)
CirrhosisToxins
(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 +erlotinib
Combination 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
Genotox
ic
Promoting agents
Carcinogenic agents
The “N-nitrosodiethylamine” model
DEN
act
s in
2 d
iffere
nt
ways
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.
THANK YOU