Hepatocellular Carcinoma Hepatocellular Carcinoma (HCC)(HCC)

DefinitionDefinition: :

Hepatocellular carcinoma is a primary malignancy Hepatocellular carcinoma is a primary malignancy of the hepatocyte , also known as liver cell of the hepatocyte , also known as liver cell carcinoma .carcinoma .

Types of HCC :Types of HCC :

1.1.Solitary HCC [ unifocal ] is the most common type Solitary HCC [ unifocal ] is the most common type usually massive tumor . usually massive tumor .

2.2. Multinodular [ multifocal ] Multinodular [ multifocal ] made of nodules of made of nodules of variable size .variable size .

3.3.Diffuse Diffuse sometimes involve the entire liver . sometimes involve the entire liver .

EpidemiologyEpidemiology: :

-Hepatocellular carcinoma is the 5th most common Hepatocellular carcinoma is the 5th most common cancer in men and the 8th most common cancer in cancer in men and the 8th most common cancer in women worldwide .women worldwide .

-The incidence of hepatocellular carcinoma The incidence of hepatocellular carcinoma worldwide varies according to the prevalence of worldwide varies according to the prevalence of hepatitis B and C infections .hepatitis B and C infections .

- More than 85% of cases occur in Asia and sub-- More than 85% of cases occur in Asia and sub-Saharan Africa in which HBV is endemic , they Saharan Africa in which HBV is endemic , they have incidences as high as 120 cases per 100,000 have incidences as high as 120 cases per 100,000 persons .persons .

The risk factors of HCC may involve :The risk factors of HCC may involve :

1 – Cirrhosis : the major risk factor for HCC .1 – Cirrhosis : the major risk factor for HCC .

2 – Race : most commonly found among Asian 2 – Race : most commonly found among Asian persons .persons .

3 – Sex : more in males than females .3 – Sex : more in males than females .

4 – Age : worldwide , median age at diagnosis is 65 4 – Age : worldwide , median age at diagnosis is 65 years.years.

Hepatocellular carcinoma is rarely diagnosed in Hepatocellular carcinoma is rarely diagnosed in persons younger than 40 years . But in Asia and persons younger than 40 years . But in Asia and Africa , the peak incidence of HCC is between 20 Africa , the peak incidence of HCC is between 20 and 40 years of old .and 40 years of old .

EtiologyEtiology

The causes of HCC are :The causes of HCC are :

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

5 ) Aflatoxins which is a hepatic carcinogen , is a 5 ) Aflatoxins which is a hepatic carcinogen , is a byproduct of fungal contamination of foodstuffs , byproduct of fungal contamination of foodstuffs , derived from aspergillus flavus .derived from aspergillus flavus .

6 ) Other factors : primary biliary cirrhosis , 6 ) Other factors : primary biliary cirrhosis , androgenic steroids , primary sclerosing androgenic steroids , primary sclerosing cholangitis , 1-antitrypsin deficiency , oral cholangitis , 1-antitrypsin deficiency , oral contraceptives , and porphyria cutanea tarda.contraceptives , and porphyria cutanea tarda.  

PathophysiologyPathophysiology

PathophysiologyPathophysiology: :

- -In chronic infection of HCV , HCC occurs In chronic infection of HCV , HCC occurs almost exclusively in the setting of cirrhosisalmost exclusively in the setting of cirrhosis. .

- -In chronic infection of HBVIn chronic infection of HBV: : a. Repeated necrosis & regeneration a. Repeated necrosis & regeneration

as occurs in chronic hepatitisas occurs in chronic hepatitis. . b. The accumulation of mutations b. The accumulation of mutations

chromosomal aberrations as deletionchromosomal aberrations as deletion. . c. The DNA of HBV integrates into c. The DNA of HBV integrates into

the genome of hepatocytes the genome of hepatocytes activate proto- activate proto-oncogens & inactivate P53oncogens & inactivate P53. .

StagingStaging

• According to the Tumor , Node , and Metastases According to the Tumor , Node , and Metastases ( TNM ) staging system , the staging of HCC is as ( TNM ) staging system , the staging of HCC is as the following :the following :

• T1 - Solitary tumor without vascular invasionT1 - Solitary tumor without vascular invasion

• T2 - Solitary tumor with vascular invasion or T2 - Solitary tumor with vascular invasion or multiple tumors none more than 5 cmmultiple tumors none more than 5 cm

• T3 - Multiple tumors more than 5 cm or tumor T3 - Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic involving a major branch of the portal or hepatic vein(s)vein(s)

• T4 - Tumor(s) with direct invasion of adjacent organs T4 - Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of other than the gallbladder or with perforation of visceral peritoneumvisceral 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

Clinical Presentation & Clinical Clinical Presentation & Clinical Pathological CorrelationPathological Correlation : :

1. Silent Hepatomegaly 1. Silent Hepatomegaly may be discovered in may be discovered in CT scan .CT scan .

2. Sudden Ascites : fluids in peritoneum due to 2. Sudden Ascites : fluids in peritoneum due to peripheral arterial dilatation peripheral arterial dilatation decrease decrease effective blood volume effective blood volume activation of the activation of the Sympathetic nervous system and Rennin – Sympathetic nervous system and Rennin – Angiotensin – Aldosteron System Angiotensin – Aldosteron System promote promote renal salts and water retention renal salts and water retention formation of formation of edema encouraged by hypoalbuminaemia .edema encouraged by hypoalbuminaemia .

3. Abdominal pain .3. Abdominal pain .

4. fever 4. fever due to inflammation , most likely caused by due to inflammation , most likely caused by infection .infection .

5. Weight loss 5. Weight loss because the cancerous mass because the cancerous mass absorbs most of the nutrients .absorbs most of the nutrients .

6. Jaundice 6. Jaundice due to obstruction of bile duct due to obstruction of bile duct ( obstructive jaundice ) . In the ( obstructive jaundice ) . In the initialinitial complaint , complaint , Only 1-12 % of HCC patients manifest obstructive Only 1-12 % of HCC patients manifest obstructive jaundice. Such cases are clinically classified as " jaundice. Such cases are clinically classified as " icteric type hepatoma " , or " cholestatic type icteric type hepatoma " , or " cholestatic type of HCC " . Identification of this group of patients is of HCC " . Identification of this group of patients is important , because surgical treatment may be important , because surgical treatment may be beneficial . In the beneficial . In the latelate stage of HCC , jaundice is stage of HCC , jaundice is very commonvery common

• 7. Mass in the right hypochondrium 7. Mass in the right hypochondrium poor poor

regulation of hepatocytes replication due to regulation of hepatocytes replication due to mutation or overexpression of specific cellular mutation or overexpression of specific cellular gene ( such as β – catenin ) , or loss of gene ( such as β – catenin ) , or loss of heterozygosity of tumor suppressor gene ( such heterozygosity of tumor suppressor gene ( such as P53 ) . as P53 ) .

• 8. Increase in serum α-fetoprotein [ AFP ] in 50% 8. Increase in serum α-fetoprotein [ AFP ] in 50% of the cases of the cases as the level of AFP increases , the as the level of AFP increases , the tumor size enlarges .tumor size enlarges .

  

• Death usually occurs within 6 months of Death usually occurs within 6 months of

diagnosis from :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 4. Rupture of the tumor fatal hemorrhage . fatal hemorrhage .  

Exams and Tests

Physical examination may show an enlarged, tender Physical examination may show an enlarged, tender liverliver..Tests includeTests include::Abdominal CT scanAbdominal CT scan Abdominal ultrasoundAbdominal ultrasound Liver biopsyLiver biopsy Liver enzymes (liver function tests)Liver enzymes (liver function tests) Liver scanLiver scan Serum alpha fetoproteinSerum alpha fetoprotein Some high-risk patients may get periodic blood tests Some high-risk patients may get periodic blood tests and ultrasounds to see whether tumors are and ultrasounds to see whether tumors are developingdeveloping

Treatment

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

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