1. Hepatocellular Carcinoma (HCC)

2. Definition : Hepatocellular carcinoma is a primary malignancy of the hepatocyte, also known as liver cell carcinoma. Types of HCC : 1.Solitary HCC [ unifocal ] is the most common type  usually massive tumor. 2. Multinodular [ multifocal ]  made of nodules of variable size. 3.Diffuse  sometimes involve the entire liver.

5. Epidemiology : -Hepatocellular carcinoma is the 5th most common cancer in men and the 8th most common cancer in women worldwide. -The incidence of hepatocellular carcinoma worldwide varies according to the prevalence of hepatitis B and C infections. - More than 85% of cases occur in Asia and sub-Saharan Africa in which HBV is endemic, they have incidences as high as 120 cases per 100,000 persons.

6. The risk factors of HCC may involve : 1 – Cirrhosis : the major risk factor for HCC. 2 – Race : most commonly found among Asian persons. 3 – Sex : more in males than females. 4 – Age : worldwide, median age at diagnosis is 65 years. Hepatocellular carcinoma is rarely diagnosed in persons younger than 40 years. But in Asia and Africa, the peak incidence of HCC is between 20 and 40 years of old. Hepatocellular carcinoma is rarely diagnosed in persons younger than 40 years. But in Asia and Africa, the peak incidence of HCC is between 20 and 40 years of old.

7. Etiology The causes of HCC are : 1 ) Chronic infection with HBV is the most common cause of HCC. 2 ) Chronic infection with HCV, the risk may increase if it is associated with diabetes. 3 ) Alcohol drinking. 4 ) Hemochromatosis, especially with cirrhosis.

8. 5 ) Aflatoxins which is a hepatic carcinogen, is a byproduct of fungal contamination of foodstuffs, derived from aspergillus flavus. 6 ) Other factors : primary biliary cirrhosis, androgenic steroids, primary sclerosing cholangitis, 1-antitrypsin deficiency, oral contraceptives, and porphyria cutanea tarda.

9. Pathophysiology

11. Pathophysiology : - In chronic infection of HCV, HCC occurs almost exclusively in the setting of cirrhosis. - In chronic infection of HBV : a. Repeated necrosis & regeneration as occurs in chronic hepatitis. a. Repeated necrosis & regeneration as occurs in chronic hepatitis. b. The accumulation of mutations  chromosomal aberrations as deletion. b. The accumulation of mutations  chromosomal aberrations as deletion. c. The DNA of HBV integrates into the genome of hepatocytes  activate proto- oncogens & inactivate P53. c. The DNA of HBV integrates into the genome of hepatocytes  activate proto- oncogens & inactivate P53.

12. Staging According to the Tumor, Node, and Metastases ( TNM ) staging system, the staging of HCC is as the following :According to the Tumor, Node, and Metastases ( TNM ) staging system, the staging of HCC is as the following : T1 - Solitary tumor without vascular invasionT1 - Solitary tumor without vascular invasion T2 - Solitary tumor with vascular invasion or multiple tumors none more than 5 cmT2 - Solitary tumor with vascular invasion or multiple tumors none more than 5 cm T3 - Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s)T3 - Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s)

13. T4 - Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneumT4 - Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum N0 - Indicates no nodal involvementN0 - Indicates no nodal involvement N1 - Indicates regional nodal involvementN1 - Indicates regional nodal involvement M0 - Indicates no distant metastasisM0 - Indicates no distant metastasis M1 - Indicates metastasis presence beyond the liverM1 - Indicates metastasis presence beyond the liver

14. Clinical Presentation & Clinical Pathological Correlation : 1. Silent Hepatomegaly  may be discovered in CT scan. 2. Sudden Ascites : fluids in peritoneum due to  peripheral arterial dilatation  decrease effective blood volume  activation of the Sympathetic nervous system and Rennin – Angiotensin – Aldosteron System  promote renal salts and water retention  formation of edema encouraged by hypoalbuminaemia.

17. 3. Abdominal pain. 4. fever  due to inflammation, most likely caused by infection. 5. Weight loss  because the cancerous mass absorbs most of the nutrients. 6. Jaundice  due to obstruction of bile duct ( obstructive jaundice ). In the initial complaint, Only 1-12 % of HCC patients manifest obstructive jaundice. Such cases are clinically classified as " icteric type hepatoma ", or " cholestatic type of HCC ". Identification of this group of patients is important, because surgical treatment may be beneficial. In the late stage of HCC, jaundice is very common

18. 7. Mass in the right hypochondrium  poor regulation of hepatocytes replication due to mutation or overexpression of specific cellular gene ( such as β – catenin ), or loss of heterozygosity of tumor suppressor gene ( such as P53 ).7. Mass in the right hypochondrium  poor regulation of hepatocytes replication due to mutation or overexpression of specific cellular gene ( such as β – catenin ), or loss of heterozygosity of tumor suppressor gene ( such as P53 ). 8. Increase in serum α-fetoprotein [ AFP ] in 50% of the cases  as the level of AFP increases, the tumor size enlarges.8. Increase in serum α-fetoprotein [ AFP ] in 50% of the cases  as the level of AFP increases, the tumor size enlarges.

19. Death usually occurs within 6 months of diagnosis from :Death usually occurs within 6 months of diagnosis from : 1. Prolonged cachexia.1. Prolonged cachexia. 2. GIT bleeding.2. GIT bleeding. 3. Liver failure.3. Liver failure. 4. Rupture of the tumor  fatal hemorrhage.4. Rupture of the tumor  fatal hemorrhage.

20. Exams and Tests Physical examination may show an enlarged, tender liver. Tests include: Abdominal CT scan Abdominal CT scan Abdominal ultrasound Abdominal ultrasound Liver biopsy Liver biopsy Liver enzymes (liver function tests) Liver scan Liver scan Serum alpha fetoprotein Serum alpha fetoprotein Some high-risk patients may get periodic blood tests and ultrasounds to see whether tumors are developing

21. Treatment Aggressive surgery or a liver transplant can successfully treat small or slow-growing tumors if they are diagnosed early. However, few patients are diagnosed early. Chemotherapy and radiation treatments are not usually effective. However, they may be used to shrink large tumors so that surgery has a greater chance of success. Sorafenib toslate (Nexavar), an oral medicine that blocks tumor growth, is now approved for patients with advanced hepatocellular carcinoma.

22. Thanks