Hepatocellular carcinoma
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Hepatocellular carcinoma (HCC, also called hepatoma) is a primary malignancy (cancer) of the liver. Most cases are secondary to either hepatitis infection (usually hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis).
Treatment options and prognosis are dependent on many factors but especially on tumor size and staging.
In Sub-Saharan Africa the commonly accepted prognosis is a median survival of 3 months from diagnosis. However, this is due to late presentation with large tumours.
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Epidemiology
The epidemiology of HCC exhibits two rough patterns, one in the Third World and another in the West.
Third World
In some parts of the world, such as Sub-Saharan Africa and Southeast Asia (and especially Taiwan and China) HCC is the commonest cancer, generally affecting men more than women, and with an age of onset between late teens and 30's. This variability is in part due to the different patterns of Hepatitis B transmission in different populations - infection at or around birth (as in Taiwan) predispose to earlier cancers than if people are infected later. The time between hepatitis B infection and development into HCC can be years even decades, but from diagnosis of HCC to death the average survival period is only 5.9 months, according to one Chinese study during the 1970-80s. HCC is one of the deadest cancers in China. Another unique type of HCC is not developed from Hepatitis B, but by eating Aspergillus flavus-infected food (especially peanuts and corns stored during prolonged wet seasons) which produces aflatoxin, a poison proven to increase risk of HCC.
Western countries
Most malignant tumors of the liver discovered in Western patients are metastases (spread) from tumors elsewhere. In the West, HCC is generally seen as rare cancer, normally of those with pre-existing liver disease. It is often detected by ultrasound screening, and so presents to health-care facilities much earlier than in Sub-Saharan Africa, for example.
Diagnosis, screening and monitoring
In the western world, hepatocellular carcinoma (HCC) most commonly appears in a patient with chronic viral hepatitis (hepatitis B or hepatitis C, 20%) or 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 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
Both calcifications and intralesional fat may be appreciated.
In patients who have a contrast agent allergy or poor renal function, an MRIs can of the abdomen is a more costly but effective substitute.
Once imaged, diagnosis is confirmed by percutaneous biopsy and histopathologic analysis.
Pathology
Macroscopically, liver cancer appears as a nodular or infiltrative tumor. The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). Tumor nodules are round to oval, grey or green (if the tumor produces bile), well circumscribed but not encapsulated. The diffuse type is poorly circumscribed and infiltrates the portal veins, or the hepatic veins (rarely).
Microscopically, there are four architectural and cytological types (patterns) of hepatocellular carcinoma: fibrolamellar, pseudoglandular (adenoid), pleomorphic (giant cell) and clear cell. In well differentiated forms, tumor cells resemble hepatocytes, form trabeculae,cords and nests, and may contain bile pigment in cytoplasm. In poorly differentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, giant. The tumor has a scant stroma and central necrosis because of the poor vascularization.1 (http://www.pathologyatlas.ro/Hepatocellular%20Carcinoma.html)
Staging and prognosis
Important features that guide treament 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.
Treatment
Most of the research done on HCC reflects a very Western population, which limits the applicability of published studies to much of the world.
- Surgery to remove the tumor can be use to treating small or slow-growing tumors if they are diagnosed early. Liver transplantation is used in more advanced disease limited to the liver.
- Percutaneous ethanol injection (PEI) Among nonsurgical options, this is usually the treatment of choice for patients with small (3 cm or less in diameter) tumors.
- Transcatheter arterial chemoembolization (TACE) is usually perform in the treatment of large tumors (larger than 3 cm and less than 4 cm in diameter) most frequently performed by intraarterially injecting an infusion of antineoplastic agents mixed with iodized oil (such as Lipiodol).
- Radiofrequency ablation (RFA) uses high frequency radio-waves to ablate the tumour.
- Combined PEI and TACE can used for tumors larger than 4 cm in diameter, although some Italian groups have had success with larger tumours using TACE alone.
Other treatments have been tried, including tamoxifen, but none seem to have a great impact.
Future directions
Current research includes the search for the genes that are disregulated in HCCTemplate:Ref. As similar research is yielding results in various other malignant diseases, it is hoped that identifying the abberant genes and the resultant proteins could lead to the identification of pharmacological interventions for HCC.
Reference
- Template:Note Genetic research in HCC (http://liver.stanford.edu/index2.asp?lang=eng&page=res_recpub) (Stanford Asian Liver Center)
External links
Research links
- Asian Liver Center at Stanford University (http://livercancer.stanford.edu/)
- MD Anderson Liver Cancer Homepage (http://www.mdanderson.org/diseases/liver/)
- HCC article by Howard J. Worman, MD, Columbia University (http://cpmcnet.columbia.edu/dept/gi/carcinoma.html)
- MedlinePlus (http://www.nlm.nih.gov/medlineplus/ency/article/000280.htm) article about HCC
- Atlas of Pathology (http://www.pathologyatlas.ro/Hepatocellular%20Carcinoma.html) (photos)
- NCI Liver Cancer Homepage (http://www.cancer.gov/cancertopics/types/liver)
- HCC Clinical Trials Search Engine (http://researchportfolio.cancer.gov/cgi-bin/projectlist.pl?SID=339421)
Patients' sites
- Liver Cancer Toolbox - In Memory of 2nd Lt. Andrew Torres (http://liver.andrewtorres.org)
- Treatment resources - In Memory of Adrienne Wilson (http://www.bluefaery.org/)
- Liver Cancer Support Group Online (http://listserv.acor.org/archives/liver-onc.html)
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