سرطان الكبد Hepatocellular carcinoma

[center][color="Blue"][size=24]Hepatocellular carcinoma (HCC, also called malignant hepatoma) is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis).[1]

Compared to other cancers, HCC is quite a rare tumor in the United States. In countries where hepatitis is not endemic, most malignant cancers in the liver are not primary HCC but metastasis (spread) of cancer from elsewhere in the body, e.g., the colon. Treatment options of HCC and prognosis are dependent on many factors but especially on tumor size and staging. Tumor grade is also important. High-grade tumors will have a poor prognosis, while low-grade tumors may go unnoticed for many years, as is the case in many other organs, such as the breast, where a ductal carcinoma in situ (or a lobular carcinoma in situ) may be present without any clinical signs and without correlate on routine imaging tests, although in some occasions it may be detected on more specialized imaging studies like MR mammography


Signs and symptoms

HCC may present with jaundice, bloating from ascites, easy bruising from blood clotting abnormalities or as loss of appetite, unintentional weight loss, abdominal pain,especially in the upper -right part, nausea, emesis, or fatigue.[2]



Risk factors

The main risk factors for hepatocellular carcinoma are
Alcoholism
Hepatitis B
Hepatitis C
Aflatoxin
Cirrhosis of the liver
Hemochromatosis
Wilsons disease (while some theorize the risk increases,[3] case studies are rare[4] and suggest the opposite where Wilson's disease actually may confer protection[5])
Type 2 Diabetes (probably aided by obesity)[6]

Ther risk of hepatocellular carcinoma in type 2 diabetics is greater (from 2.5[6] to 7.1[7] times the non diabetic risk) depending on the duration of diabetes and treatment protocol. A suspected contributor to this increased risk is circulating insulin concentration such that diabetics with poor insulin control or on treatments that elevate their insulin output (both states that contribute to a higher circulating insulin concentration) show far greater risk of hepatocellular carcinoma than diabetics on treatments that reduce circulating insulin concentration.[6][7][8] On this note, some diabetics who engage in tight insulin control (by keeping it from being elevated) show risk levels low enough to be indistinguishable from the general population.[7][8] This phenomenon is thus not isolated to diabetes mellitus type 2 since poor insulin regulation is also found in other conditions such as metabolic syndrome (specifically, when evidence of non alcoholic fatty liver disease or NAFLD is present) and again there is evidence of greater risk here too.[9][10] While there are claims that anabolic steroid abusers are at greater risk[11] (theorized to be due to insulin and IGF exacerbation[12][13]), the only evidence that has been confirmed is that anabolic steroid users are more likely to have hepatocellular adenomas (a benign form of HCC) transform into the more dangerous hepatocellular carcinoma.[14][15]

When hepatocellular adenomas grow to a size of more than 6–8 cm, they are considered cancerous and thus become a risk of hepatocellular carcinoma. Although hepatocellular carcinoma most commonly affects adults, children who are affected with biliary atresia, infantilecholestasis, glycogen-storage diseases, and other cirrhotic diseases of the liver are predisposed to developing hepatocellular carcinoma.

Children and adolescents are unlikely to have chronic liver disease, however, if they suffer from congenital liver disorders, this fact increases the chance of developing hepatocellular carcinoma.[16]

Pathogenesis

Hepatocellular carcinoma, like any other cancer, develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and/or results in the cell avoiding apoptosis. In particular, chronic infections of hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the body's own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders.[17] While this constant cycle of damage followed by repair can lead to mistakes during repair which in turn lead to carcinogenesis, this hypothesis is more applicable, at present, to hepatitis C. Chronic hepatitis C causes HCC through the stage of cirrhosis. In chronic hepatitis B, however, the integration of the viral genome into infected cells can directly induce a non-cirrhotic liver to develop HCC. Alternatively, repeated consumption of large amounts of ethanol can have a similar effect. Besides, cirrhosis is commonly caused by alcoholism, chronic hepatitis B and chronic hepatitis C. The toxin aflatoxin from certain Aspergillus species of fungus is a carcinogen and aids carcinogenesis of hepatocellular cancer by building up in the liver. The combined high prevalence of rates of aflatoxin and hepatitis B in settings like China and West Africa has led to relatively high rates of heptatocellular carcinoma in these regions. Other viral hepatitides such as hepatitis A have no potential to become a chronic infection and thus are not related to hepatocellular carcinoma

Diagnosis

Hepatocellular carcinoma (HCC) most commonly appears in a patient with chronic viral hepatitis (hepatitis B or hepatitis C, 20%) or/and with cirrhosis (about 80%). These patients commonly undergo surveillance with ultrasound due to the cost-effectiveness.

In patients with a higher suspicion of HCC (such as rising alpha-fetoprotein and des-gamma carboxyprothrombin levels), the best method of diagnosis involves a CT scan of the abdomen using intravenous contrast agent and three-phase scanning (before contrast administration, immediately after contrast administration, and again after a delay) to increase the ability of the radiologist to detect small or subtle tumors. It is important to optimize the parameters of the CT examination, because the underlying liver disease that most HCC patients have can make the findings more difficult to appreciate.

On CT, HCC can have three distinct patterns of growth:
A single large tumor
Multiple tumors
Poorly defined tumor with an infiltrative growth pattern

A biopsy is not needed to confirm the diagnosis of HCC if certain imaging criteria are met.

The key characteristics on CT are hypervascularity in the arterial phase scans, washout or de-enhancement in the portal and delayed phase studies, a pseudocapsule and a mosaic pattern. Both calcifications and intralesional fat may be appreciated.

CT scans use contrast agents, which are typically iodine or barium based. Some patients are allergic to one or both of these contrast agents, most often iodine. Usually the allergic reaction is manageable and not life threatening.

An alternative to a CT imaging study would be the MRI. MRI's are more expensive and not as available because fewer facilities have MRI machines. More important MRI are just beginning to be used in tumor detection and fewer radiologists are skilled at finding tumors with MRI studies when it is used as a screening device. Mostly the radiologists are using MRIs to do a secondary study to look at an area where a tumor has already been detected. MRI's also use contrast agents. One of the best for showing details of liver tumors is very new: iron oxide nano-particles appears to give better results. The latter are absorbed by normal liver tissue, but not tumors or scar tissue.

In a review article of the screening, diagnosis and treatment of hepatocellular carcinoma, 4 articles were selected for comparing the accuracy of CT and MRI in diagnosing this malignancy.[18] Radiographic diagnosis was verified against post-transplantation biopsy as the gold standard. With the exception of one instance of specificity, it was discovered that MRI was more sensitive and specific than CT in all four studies

Staging

Important features that guide treatment include: -
size
spread (stage)
involvement of liver vessels
presence of a tumor capsule
presence of extrahepatic metastases
presence of daughter nodules
vascularity of the tumor

MRI is the best imaging method to detect the presence of a tumor capsule

Prevention

Since hepatitis B or C is one of the main causes of hepatocellular carcinoma, prevention of this infection is key to then prevent hepatocellular carcinoma. Thus, childhood vaccination against hepatitis B may reduce the risk of liver cancer in the future.[20]

In the case of patients with cirrhosis, alcohol consumption is to be avoided. Also, screening for hemochromatosis may be beneficial for some patients.[21]


Management
This article's factual accuracy may be compromised due to out-of-date information. Please help improve the article by updating it. There may be additional information on the talk page. (January 2010)

Liver transplantation to replace the diseased liver with a cadaveric liver or a living donor graft. Historically low survival rates (20%-36%). During 1996–2001 the rate had improved to 61.1% , likely related to adoption of the Milan criteria at US transplantation centers. Expanded Shanghai criteria in China resulted in overall survival and disease-free survival rates similar to the Milan criteria.[22] Studies from the late 2000 obtained higher survival rates ranging from 67% to 91%.[23] If the liver tumor has metastasized, the immuno-suppressant post-transplant drugs decrease the chance of survival. Considering this objective risk in conjunction with the potentially high rate of survival, some recent studies conclude that: "LTx can be a curative approach for patients with advanced HCC without extrahepatic metastasis".[24] For those reasons, and others, it is considered nowadays that patient selection is a major key for success.[25]
A new receptor tyrosine kinase inhibitor, Sorafenib may be used in patients with advanced hepatocellular carcinoma.[26] Sorafenib is a small molecule that inhibits tumor-cell proliferation and tumor angionesis. It has been shown in a Spanish phase III clinical trial to add two months to the lifespan of late stage HCC patients with well preserved liver function.[27] It also increases the rate of apoptosis in other tumor models. The results indicated that single-agent sorafenib might have a beneficial therapeutic effect. In this study, for instance, the median overall survival was of 9.2 months and the median time to progression was of 5.5 months. Also, the survival benefit represented a 31% relative reduction in the risk of death.[28]
Surgical resection to remove a tumor together with surrounding liver tissue while preserving enough liver remnant for normal body function. This treatment offers the best prognosis for long-term survival, but unfortunately only 10-15% of patients are suitable for surgical resection. This is often due to extensive disease or poor liver function. Resection in cirrhotic patients carries high morbidity and mortality. The expected liver remnant should be more than 25% of the total size for a non-cirrhotic liver, while that should be more than 40% of the total size for a cirrhotic liver. The overall recurrent rate after resection is 50-60%.
Percutaneous ethanol injection (PEI) well tolerated, high RR in small (8 cm), presence of portal vein thrombus, tumors with portal-systemic shunt and patients with poor liver function.
Radiofrequency ablation (RFA) uses high frequency radio-waves to destroy tumor by local heating. The electrodes are inserted into the liver tumor under ultrasound image guidance using percutaneous, laparoscopic or open surgical approach. It is suitable for small tumors (