Hepatocellular carcinoma

From Freepedia

Hepatocellular carcinoma
ICD-10 code: C22
ICD-9 code: 155

Hepatocellular carcinoma (HCC, also called hepatoma or liver cancer) is a primary malignancy (cancer) of the liver. Most cases of HCC are secondary to either hepatitis infection (usually hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis). In countries where hepatitis is not endemic, most 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.

In Sub-Saharan Africa and most other Third World countries the commonly accepted prognosis is a median survival of 3 months from diagnosis. This is partially due to late presentation with large tumours, but also the lack of medical expertise and facilities.

Contents

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 most common 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, or 3 months (median survival time) in Sub-Saharan Africa according to Manson's textbook of tropical diseases. HCC is one of the deadest cancers in China. Food infected with Aspergillus flavus (especially peanuts and corns stored during prolonged wet seasons) which produces aflatoxin, poses another risk factor for 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 can be discovered health-care facilities much earlier than in developing regions such as Sub-Saharan Africa.

Diagnosis, screening and monitoring

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 MRI scan 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

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

  • Liver transplantation to replace the liver with a cadaver liver or a live donor lobe. Historically low survival rates (20%-36%) recent improvement (61.1%; 1996-2001), likely related to adoption of Milan criteria at US transplantation centers. If the tumor disease has metastasized, the immuno-suppresent post-transplant drugs decrease the chance of survival.
  • Surgical Resection to remove the tumor can be use to treating small or slow-growing tumors if they are diagnosed early. This treatment offers the best prognosis for long-term survival but unfortunately is possible in only 10-15% of cases. Resection in cirrhotic patients carries high morbidity and mortality.
  • Percutaneous ethanol injection (PEI)PEI well tolerated, high RR in small (< 3 cm) solitary tumors; as of 2005, no randomized trial comparing resection to percutaneous treatments; recurrence rates similar to those for postresection.
  • 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). As of 2005, multiple trials show objective tumor responses and slowed tumor progression but questionable survival benefit compared to supportive care; greatest benefit seen in patients with preserved liver function, absence of vascular invasion, and smallest tumors
  • Radiofrequency ablation (RFA) uses high frequency radio-waves to ablate the tumour.
  • Intra-arterial iodine-131–lipiodol administration Efficacy demonstrated in unresectable patients, those with portal vein thrombus. This treatment is also used as adjuvant therapy in resected patients (Lau at et, 1999). It is believed to raise the 3-year survival rate from 46 to 86%. This adjuvant therapy is in phase III clinical trials in Singapore and is available as a standard medical treatment to qualified patients in Hong Kong.
  • 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.
  • High frequency ultrasound (HIFU) (not to be confused with normal diagnostic ultrasound) is a new technique which uses much more powerful ultrasound to treat the tumour. Still at a very experimental stage. Most of the work has been done in China. Some early work is being done in Oxford and London in the UK.
  • Hormonal therapy Antiestrogen therapy with tamoxifen studied in several trials, mixed results across studies, but generally considered ineffective Octreotide (somatostatin analogue) showed 13-month MS v 4-month MS in untreated patients in a small randomized study; results not reproduced
  • Chemotherapy Adjuvant: No randomized trials showing benefit of neoadjuvant or adjuvant systemic therapy in HCC; single trial showed decrease in new tumors in patients receiving oral synthetic retinoid for 12 months after resection/ablation; results not reproduced. Clinical trials have varying results.[1].
  • Palliative: Regimens that included doxorubicin, cisplatin, fluorouracil, interferon, epirubicin, or taxol, as single agents or in combination, have not shown any survival benefit (RR, 0%-25%); a few isolated major responses allowed patients to undergo partial hepatectomy; no published results from any randomized trial of systemic chemotherapy
  • Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial embolization/chemoembolization; PFS, progression-free survival; PS, performance status; HBV, hepatitis B virus; PEI, percutaneous ethanol injection; RR, response rate; MS, median survival.

Future directions

Current research includes the search for the genes that are disregulated in HCC[2], protein markers, and other predictive biomarkers. [3]. 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

  • ^  Genetic research in HCC (Stanford Asian Liver Center)
  • ^  [4] (American Society of Clinical Oncology, 2005 Annual Meeting, Abstracts on Hepatobiliary Cancer)
  • ^  [5] (Journal of Clinical Oncology - April 2005, Special Issue on MOLECULAR ONCOLOGY: Receptor-Based Therapy)
  • ^  [6] (Lau et al, "Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial", Lancet, Vol. 353, pp. 797-801, 1999.)

External links

Research links

Patients' sites



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