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Chapter 14:
Liver
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16. Neoplasms of the Liver / L.J. Worobetz page 550

Neoplasms of the liver can be divided into benign and malignant, with malignant tumors being either primary or secondary from a cancer that has metastasized from elsewhere. The sites from which metastases occur frequently include lung, colon, pancreas, breast, stomach and ovary. In North America, primary hepatic neoplasms are uncommon and metastatic tumors commonly seen, whereas worldwide, especially in areas such as the Far East, hepatocellular carcinoma (HCC) is much more prevalent than metastatic disease.

 

16.1 Benign Tumors of the Liver page 550

Benign tumors of in the liver are detected more frequently than in the past, in part as a result of the increased use of diagnostic imaging tests, including ultrasound and CT scanning, for reasons unrelated to the tumors. Benign tumors are divided into three categories: hepatocellular, cholangiocellular and non-epithelial.

Hepatocellular adenomas are benign tumors seen primarily in females in their third and fourth decades. Their increased prevalence paralleled the introduction of the oral contraceptive, suggesting a hormonal influence in their pathogenesis. The tumors may be multiple, usually involving the right lobe, and may be > 10 cm in diameter. Clinical features include an asymptomatic presentation, pain, palpable mass or features of hemorrhage into the tumor. Diagnosis is usually established with imaging techniques including ultrasound, CT scanning, angiography and radionuclear scanning. The tumor is often hypervascular but with hypovascular areas. The risk of malignancy is 10% with an increased risk in the larger, multiple tumors. Management includes stopping oral contraceptives and resection of larger, symptomatic tumors.

Focal nodular hyperplasia differs from the adenoma in that this solid tumor has a fibrous core and includes other cell types such as atypical hepatocytes, Kupffer's cells and inflammatory cells. The lesion is vascular and because of the presence of Kupffer's cells will appear as an area of increased uptake on radionuclear scanning. Although also more common in women, it does not appear related to the oral contraceptive. No treatment is needed if the patient is asymptomatic.

Hemangiomas of the liver are seen in about 0.5-7% of the general population. These are usually detected by imaging techniques done for other reasons. These vascular lesions are usually asymptomatic and are more common in women. The lesion does not require any treatment as there is no malignant potential and hemorrhage is rare. The vascular nature can be confirmed by red blood cell-labeled nuclear scanning.

 

16.2 Primary Hepatocellular Carcinoma (HCC) page 551

Although HCC is one of the most common tumors worldwide, it represents only 1-2% of malignant tumors in North America. The tumor is more commonly seen in males and usually arises from areas of long-standing liver injury with liver necrosis and repair, as in the cirrhotic liver. The risk of developing HCC is greatest in patients with chronic hepatitis B and C infections, hemochromatosis and cirrhosis from a1-antitrypsin deficiency. Hepatitis B can predispose to hepatoma in either a cirrhotic or noncirrhotic liver by the integration of the hepatitis B-DNA into portions of the human genome within the hepatocytes where growth-modifying genes are present. Recent studies suggest that in cases of HCC, HCV is substantially more common than HBV. HCC is not often seen in patients with alcoholic cirrhosis who continue to drink, unless the alcoholic has coexisting viral hepatitis. Hepatic co-carcinogens that appear to play a role in HCC include aflatoxin and vinyl chloride.

The clinical recognition of HCC may be difficult, as the tumors often occur in patients with underlying cirrhosis, and the signs and symptoms may suggest progression of underlying liver disease. The more common presentations include deterioration of the known cirrhotic with rapid weight loss, an enlarging liver with a mass, abdominal pain or bloody ascites. A friction rub or bruit may be present over the liver. Patients may present with one of the many paraneoplastic syndromes, including erythrocytosis, hypercalcemia, dysproteinemia or hypoglycemia. Serum a-fetoprotein levels are greater than 500 µg/L in 70-80% of cases. Ultrasound and CT scan imaging are often used to identify the mass, but occasionally radionuclear scanning (using gallium) or x-ray angiography may help further define the nature of the mass lesion and provide important operative details. A biopsy of the mass or examination of the ascitic fluid for cytology may yield a conclusive diagnosis.

Treatment is disappointing. Surgical resection represents the only opportunity for cure, but resection is often complicated by the presence of underlying cirrhosis, the occasional multicentric nature of the tumor and the presence of micrometastases. Up to 70% of patients already have metastatic disease at the time of diagnosis. The mean survival from the time of diagnosis is approximately 6 to 12 months. Liver transplantation may be considered, but recurrence of tumor and presence of metastases after transplantation have limited its usefulness. Other experimental approaches include hepatic artery embolization with chemotherapy, immunotherapy with monoclonal antibodies tagged with chemotherapy and gene therapy with cytotoxic agents.

Screening strategies include ultrasound and/or a-fetoprotein determinations every 6 months in high-risk patients. This approach clearly identifies tumors at an earlier stage but has not yet been shown to improve morbidity or mortality rates.

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