hepatocellar carcioma

1. Hepatocellular carcinomaDiagnosis and management By Mohammed Mahmoud, MD

2. Liver Cancer Incidence:Sixth Most Common Cancer Worldwide1 Lung 1,549,121 • HCC is the most common primary liver malignancy in adults2 Breast 1,301,867 Colon/Rectal 1,167,020 Stomach 1,066,543 Prostate 782,647 Liver 711,128 Cervix Uteri 559,094 Esophagus 529,283 Leukemia 330,963 Bladder 314,256 Ovary 230,555 Corpus Uteri 226,787 Oral Cavity 200,774 Non-Hodgkin's Lymphoma 196,298 0 200,000 400,000 600,000 800,000 1,000,000 1,200,000 1,400,000 1,600,000 1,800,000 1. Garcia M, et al. American Cancer Society, 2007. www.cancer.org. Accessed March 20, 2008. 2. Perz JF, et al. J Hepatol. 2006;45:529-538.

3. Incidence of HCC Is Increasing1 Year 1983-1985 1995-1996 1976-1979 1992-1995 1975 2004 1975-1977 1996-1998 Australia(men)2 France (men)*3 UK4 US5 *Primary liver cancer. UK=United Kingdom; US=United States. 1. El-Serag HB, et al. Gastroenterology. 2007;132:2557–2576; 2. Law MG, et al. Med J Aus. 2000;173:403-405; 3. Benhamiche A-M, et al. J Hepatol. 1998;29:802-806; 4.http://info.cancerresearchuk.org/cancerstats/types/liver/incidence/?a=5441. Accessed August 2008; 5. El-Serag HB, et al. Ann Intern Med. 2003;139:817-823.

4. Liver Cancer: Estimated Mortality (2007) 1,600,000 • Liver cancer is the third most common cause of cancer-related death 1,351,034 1,400,000 1,200,000 1,000,000 800,230 Number of estimated deaths 800,000 679,871 602,967 600,000 400,000 200,000 0 Lung and bronchus Stomach Liver Colon and rectum Garcia M, et al. American Cancer Society, 2007. www.cancer.org. Accessed August, 2008.

5. HCC in Egypt • HCC is a common disorder in Egypt requiring further considerations. Hepatitis C is a major health problem in Egypt leading to progression from chronic active hepatitis to HCC. it is estimated that the problem of HCC will increase until it reaches its peak in the year 2018.

6. Risk factors • Infectious: • Chronic hepatitis C. • Chronic hepatitis B. • Chronic delta hepatitis. • Metabolic diseases: • NAFLD • Hereditary hemochromatosis. • α-1-antitrypsin deficiency. • Porphyria cutanea tarda. • Hereditary tyrosinemia • Toxins: • Alcohol. • Aflatoxin B1. • Pesticides. • Hormones: • Anabolic steroids. • Estrogens. • Underlying liver disease: • Cirrhosis of any cause.

7. Aflatoxin is a mycotoxins produced by the fungi Aspergillus flavus and Aspergillus parasiticus, which contaminate food stored in humid conditions (corn, soybeans and peanuts).

8. Oncogenesis • Activation of protooncogene • Inactivation of Tumor suppressor gene • DNA mismatch repair genes • Telomerase activation

9. Oncogenesis • Activation of protooncogene: It is gene encoding for proteins which are either growth factor, growth factor receptors, 2ry messenger or even DNA binding proteins that participate in normal cell proliferation and it would act as a promotor of abnormal cell growth if mutated e.g. HBV activate K-ras and insulin like growth factor II.

10. Oncogenesis • Overexpression of certain growth factors was found in HCC, including: • Insulin-like growth factor II (IGF-II). • Transforming growth factor (TGF). • Hepatocyte growth factor (HGF). • Insulin receptor substrate 1 (IRS-II).  

11. Oncogenesis • Inactivation of Tumor suppressor gene e.g. P53 Genes encoding protein that restrict undue cellular proliferation, induce repair or self destruction (apoptosis) of cell containing damaged DNA. e.g. P53 is DNA binding protein which induce expression of other genes, P53 induce expression of DNA repairing enzymes, if DNA repair is too slow or can not be done, it induces apoptosis promotor genes e.g BAX which causes apoptosis of cells with damaged DNA.

12. Oncogenesis • Mutation of tumor suppressor genes results in uncontrolled cell proliferation of cells with active onocogene. e.g. HBV and Aflatoxin inactivates P53.

13. Oncogenesis • DNA mismatch repair genes Defective DNA mismatch repair can lead to the accumulation of mutations and in the cellular genome and thus increase the chance of malignant transformation. HBxAg interferes with the component of DNA repair machinary. • Telomerase activation The progressive shortening of chromosome ends, or telomeres, accompanies normal cell division and may contribute to cellular aging and serve as a control mechanism against unregulated cellular proliferation. Correlation between certain types of cancer and the expression of telomerase (enzyme preventing the shortening of telomeres) was found. Telomerase activity was found in 85% of HCC tissues.

14. Clinical picture • Asymptomatic presentation: Up to 40% of patients are asymptomatic at the time of presentation. Because of the surveillance programs, tumors can be detected as early as (0.5-1 cm in diameter).

15. Clinical picture • The most common presentation of HCC is the triad of: • Right hypochondrial pain: dull aching in nature, sometimes radiates to the shoulder, sudden attacks of more severe pain may be caused by spontaneous bleeding in to the tumor. • Weight loss. • Hepatomegaly: often massive, the liver is hard in consistency

16. Complications • Hepatic decompensation: In a patient with previously controlled liver cirrhosis, developing ascites, refractory or haemorrhagic, jaundice or encephalopathy. • Gastrointestinal Haemorrhage: 10% of the patients present with GIT bleeding, 40% of which bleeding comes from varices, bleeding is more common in cases of portal vein invasion by the tumor.Reccurent variceal haemorrhage may be the first presentation.

17. Complications • Tumor rapture (hemoperitoneum): - Spontaneous rapture presenting with sudden onset of abdominal pain and swelling, it may the presenting feature though it occurs late during the course of the disease. - The patient presents with shock, rigid silent abdomen, paracentesis reveals blood stained fluid or frank blood. • Spread to involve the hepatic veins: leading to a picture of Budd -Chiarri syndrome with tense ascites. • Obstructive jaundice: Compression of the bile ducts by the tumor, in approximately 1/2 of the cases the obstruction is extrahepatic, direct growth of the tumor in the bile duct, bleeding of the tumor in the bile duct (hemobilia).

18. Complications • Endocrine and para-neoplastic presentation: - Erythrocytosis: due to production of erythropoietin or erythropoietin like substance. - Hypoglycemia: Occurring during the advanced stage of the tumor growth. Symptomatic severe hypoglycemia early in the course of the disease not responding to treatment. - Hypercalcemia, Hyperthyroidism, Gynecomastia, FUO or unexplained diarrhea.

19. SPECIAL FORM OF HCC: • Fibrolamellar type of HCC: - Young age of presentation (around 20years). - Normal AFP. - Histological picture of fibrous bands & oesinophilic tumour cells. - Carries a better prognosis.  • Sclerosing variant of HCC: - Worse prognosis. - Usually presented with para-neoplastic symptoms (hypoglycaemia).

20. SPECIAL FORM OF HCC • HCC in non-cirrhotic liver: - 10-20% of the cases arise in normal liver, and the patient had better survival. - Higher incidence in females and young age of presentation. - AFP is usually high and tumour size is usually large. - Surgical resection is the treatment of option.

21. I found a mass on screening How to diagnose?

22. Diagnosis of HCC

23. Diagnosis of HCC

24. Diagnosis of HCC

25. Triphasic CT Before After ttt

26. Dynamic MRI

27. Contrast Enhanced Power Doppler

28. Thanks to God I diagnosed the mass as HCC Now, who will treat?

29. BCLC guidelines for management of HCC

30. Cont.

31. Cont.

32. Percutaneous ablations therapies (PATS) • Chemical ablation • Percuanteous ethanol injection (PEI) • Percutaneous acetic acid injection (PAI) • Thermal ablation • Radiofrequency ablation (RF) • Microwave ablation. • Hot saline injection. • HIFU • Cryoblation

33. Chemical ablation of HCC • Direct injection of absolute alcohol into the tumor causes immediate dehydration of the cytoplasm with consequent coagulation necrosis followed by fibrous reaction. It also causesintramural arterial thrombosis followed by tumoral ischemia. • Acetic acid 50% injection produces same effect as ethanol in addition it infiltrates the intratumoral septae and the capsule of the tumor.

34. Injection needles

35. Techniques Free hand Needle guide

37. Advantages Simple Inexpensive Repeatable Excellent results in small HCCs Low mortality (0.09%) Suitables for areas in which RF is risky (near GB, CBD, liver surface) or ineffective (close to a major vessel) Disadvantages Relatively larger number of sessions Poor results in medium and large HCCs Chemical ablation of HCC

38. Thermal ablation of HCC • Radiofrequency ablation (RF) • Microwave ablation. • Hot saline injection. • HIFU.

39. Percuantous radiofrequency ablation of HCC

40. Types of RF electrodes Expandable Cool tip

41. COOL tip RFA Cool tip Cool tip

42. Expandable RFA

43. RFA • Excellent ablation results in small HCC. • For Medium size lesions (3-5cm) multiple overlapping sequential ablations may be necessary to ensure adequate margins. • Reported local recurrence rate 10-20%. • RFA is safe with lower mortality rate than cryoablation, complications include (pleural effusion, peritoneal bleeding). • Not suitable for subcapsular (peritoneal seeding), near GB, near major vessels (heat sink) and near abdominal viscera.

44. Microwave ablation • Volumetric heating is accomplished by friction as microwave propagates through the tissue and cause water molecules to rotate rapidly. • It has the following advantages over RFA • Higher tissue temperatures • Shorter treatment time • Reduced effect by vascular mediated cooling.

45. High intensity focused ultrasound (HIFU) • The HIFU System applies high intensity focused ultrasound to treat tumour. Using extracorporeal ultrasound as a treatment modality, it destroys the cancer foci non-invasively. Ultrasound can penetrate biological tissue and can be accurately focused. • High energy produced at the focal area ablates the cancer foci causing coagulative necrosis and therefore destroying its capacity to proliferate and metastasize.

46. Cryoablation • Cryosurgery is a technique where liquid nitrogen is circulated through a vacuum-insulated metal probe placed in the tumor. It is generally performed during laparotomy although the technique may be employed by either the laparoscopicor percutaneous route. • Cellular death results from direct freezing, denaturation of cellular proteins, cell membrane rupture, cell dehydration, and ischemic hypoxia.

47. Cryoablation • Complications include hypothermia and cryoshock syndrome; syndrome of DIC and multiple organ failure due to cytokine release

48. Transarterial chemoembolization (TACE) TACE combines embolization with directed chemotherapeutic agents including doxorubicin, mitomycin and cisplatin. Techniques used include injecting the chemotherapeutic agent into the hepatic artery alone or followed by the injection of a second substance such as a coil or gelfoam to create an arterial occlusion. Alternative techniques include suspending the chemotherapeutic agent in lipiodol, an oily contrast agent which can be used to embolize the artery.

49. TACE • TACE is used in combination with PATs for treatment of medium size HCC to give better results or as alternative to RF in areas where RF is not effective (near major vessel) or dangerous (adjacent to abdominal viscera). • TACE cannot be performed in the presence of pre existing portal vein thrombosis as it carries the risks of compromising the sole remaining hepatic blood supply, the hepatic artery.

50. TACEcomplications • Post-embolization syndrome:appears in >50% of the patients and usually self-limited in <48 hours. It presents with nausea, vomiting,fever, abdominal pain and a moderate degree of ileus. NPO and IV hydration is recommended. • Impaired liver functions, liver abscess.