Hepatocellular Carcinoma

1. Hepatocellular Carcinoma Heba Mohamed Fahmy

2. إخلاص النية • 1- التخفيف من الام و اوجاع مرضي السرطان و محاولة إيجاد علاجات تفتح باب الأمل و تكون بأقل أعراض جانبية • 2- هذا التعاون من باب تعاونوا علي البر و التقوي .... • 3- تنمية روح الفريق الواحد فيد الله مع الجماعة ... • 4- نبذ الخلافات و المشاكل بيننا و ليكن هدفنا الاسمي أن نقوي بعضنا البعض • 5- مساعدة صغار الباحثين و ضمهم إلينا بقدر المستطاع • 6- لن يكون هناك كراهية و لا حقد بيننا ..لأننا ببساطة سننجح معا أو نفشل معا • أن نسلك طريقا نلتمس فيه علما فيسهل الله لنا طريقا إلي الجنة 7-

3. 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

4. Causes

5. Signs & symptoms

6. Diagnosis

7. Treatment (Surgery)

8. Treatment (non-Surgical) should only be used where surgical therapy is not possible. • 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 • Radiofrequency ablation(RFA) • High frequency ultrasound to generate heat • good alternative ablative therapy • Useful for tumor control in patients awaiting liver transplant

9. 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)

10. 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-alfa 8)retinoids and adoptive immunotherapy (adjuvant)

11. Investigational combination therapies in HCC

12. Combinations therapy Bevacizumzb or Sorafenib + Erlotinib Sorafenib + mTOR inhibitor Early sequential therapies HCC (What’s ahead?)

13. The paper 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

14. Carcinogenic agents

15. The “N-nitrosodiethylamine” model

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

17. 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)

18. The peroxisome poliferators model • -The preroxisomepoliferator-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.

19. Thank you 