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Tumors of the Liver and Biliary System


Liver tumors

The liver filters both arterial and portal venous blood and thus is a major site for the spread of metastatic cancers, particularly those that originate in the abdomen. Metastatic liver tumors can develop after the primary tumor has been identified, or patients can present initially with the signs and symptoms of metastatic liver disease. Common primary tumors that metastasize to the liver are colon, pancreas, stomach, breast, lung, gallbladder, and bile duct tumors, and lymphoma.

The most common primary liver cancer is hepatoma, or hepatocellular carcinoma. Hepatoma often is a consequence of cirrhosis. Worldwide, chronic hepatitis B, leading to cirrhosis, is a major antecedent of hepatoma. Other primary liver malignancies are cholangiohepatocellular carcinoma and sarcoma, including angiosarcoma, leiomyosarcoma, fibrosarcoma, and mesenchymal sarcoma.

Benign tumors of the liver include hepatic hemangioma, adenoma, focal nodular hyperplasia, and focal regenerative hyperplasia.

Clinical presentation

History

Primary hepatoma often occurs in the setting of established cirrhosis. In fact, abrupt deterioration of a patient with known cirrhosis is a signal to consider the possibility of hepatoma. Other pathogenic antecedents of hepatoma include chronic hepatitis B infection, exposure to aflatoxins in food (implicated in parts of Africa and Asia), and exposure in the distant past to thorium dioxide, a radiologic contrast material. Uncommon consequences of hepatoma include fever of unknown origin, portal vein thrombosis, hypoglycemia, polycythemia, hypercalcemia, porphyria, and dysglobulinemia.

In patients with metastatic liver cancer, the primary lesion may not be known. Thus the initial presentation may be due to the metastatic disease to the liver. About half of the patients who die from malignant disease have metastases in the liver at postmortem examination.

Abdominal pain is a common complaint of patients with primary hepatoma or metastatic liver disease. Some patients have nonspecific complaints, such as anorexia, weight loss, and malaise.

Physical examination

The liver typically is enlarged and nodular and may be tender. Ascites often has developed. A friction rub heard over the liver with respiration indicates involvement of the liver capsule. Rarely, a bruit is heard, reflecting the vascular nature of most hepatomas and some metastatic tumors. Jaundice usually develops later in the course of both hepatoma and metastatic liver disease. If jaundice is present initially, it means that preexisting liver disease is present, the tumor involves much of the liver parenchyma, or a large bile duct is obstructed.

Diagnostic studies

Laboratory studies

Anemia is common in patients with liver cancer. It may be the nonspecific anemia of chronic disease or the macrocytic anemia associated with a chronic liver disorder. Bilirubin is elevated for the same reasons that the patient may be jaundiced. Elevation of alkaline phosphatase is common simply because obstruction of even the small biliary radicals causes generation and release of this enzyme. If the source of an elevated alkaline phosphatase level is in question, a 5’-nucleotidase elevation will confirm its origin in the liver. Often mild elevations of aspartate aminotransferase and alanine aminotransferase occur.

The serum alpha-fetoprotein concentration is elevated in about half of the patients with hepatoma in the United States; thus, the measurement is useful in helping to make the diagnosis. However, some patients with gonadal malignancies and metastatic disease to the liver also have elevated serum alpha-fetoprotein.

Radiologic studies include ultrasound, computed tomography, magnetic resonance imaging, dimethylphenylcarbamylmethyliminiodiacetic acid (HIDA) scan and sulfur colloid liver scan.

Many physicians proceed immediately to computed tomography in the evaluation of liver tumors after the initial blood chemistry studies have been done. The computed tomography scan has the advantage of not only providing accurate information about the liver but also identifying enlarged lymph nodes and other abnormalities of the abdominal organs. Furthermore, a computed tomography-guided needle biopsy of a liver lesion or other abdominal mass may provide important diagnostic information.

Liver biopsy

Percutaneous liver biopsy is diagnostic of liver cancer in about 80% of patients in whom alkaline phosphatase is elevated due to intrahepatic cancer. Biopsy of the liver under direct laparoscopic vision is an alternative to percutaneous liver biopsy. Laparoscopy also can assess the spread of tumor to the peritoneum, lymph nodes, and other abdominal organs.

Angiography

Celiac axis angiography can determine operability in a patient with a hepatoma or with a solitary metastatic lesion to the liver. If the computed tomography scan suggests tumor in both lobes of the liver, arteriography is not indicated. An arteriogram is helpful in differentiating a benign hemangioma from a malignant tumor when the computed tomography scan suggests a vascular lesion.

Treatment

The prognosis of both primary and metastatic liver cancer is poor. Best results are obtained after resection of a hepatoma or single metastasis that is confined to one lobe. Thus every effort should be made to define the extent of the tumor. Liver transplantation has been successful in some patients with primary hepatomas.

Most patients are offered palliation with systemic chemotherapy or intraarterial infusion of chemotherapeutic agents. Irradiation of the liver may relieve pain. Embolization of the branch of the hepatic artery that feeds the tumor to achieve tumor necrosis has been reported as a palliative treatment.

Biliary tumors

Biliary tumors include those that arise in the gallbladder and in the intra- and extrahepatic biliary system. Benign tumors are rare and include papilloma, leiomyoma, lipoma, myxoma, and fibroma. On the other hand, adenocarcinomas of the gallbladder and bile ducts (cholangiocarcinomas) are not rare, accounting for about 5% of all malignancies. The etiology of most biliary tumors is unknown, although gallbladder cancer has been linked to chronic inflammation due to gallstone disease, and, in the Orient, the liver fluke Clonorchis sinensis appears to predispose to cholangiocarcinoma.

Clinical presentation

History

Patients with cancer of the gallbladder may have symptoms that usually are associated with cholecystitis, namely, right upper abdominal pain, nausea, and vomiting. Later, they also may become anorectic, lose weight, and develop jaundice. Conversely, jaundice is the first symptom in nearly all patients with bile duct cancer. Pain, anorexia, weight loss, nausea, vomiting, and pruritus may ensue. If bile duct obstruction is complete, dark urine and pale stools develop.

Bile duct adenocarcinoma that is located at the bifurcation of the right and left hepatic ducts has been called a Klatskin’s tumor and historically has been difficult to diagnose. Patients typically present with jaundice and nonspecific symptoms of lassitude and anorexia. Modern methods of imaging the bile ducts (percutaneous transhepatic cholangiography and endoscopic retrograde cholangiography) and computed tomography have improved the diagnosis of this tumor.

Physical examination

Jaundice may be evident. A gallbladder cancer may be felt as a firm mass in the right upper quadrant. A nontender distended gallbladder suggests that the obstruction is distal to the cystic duct.

Diagnostic studies

Laboratory studies

A complete blood count and routine liver tests should be obtained. If a bile duct tumor involves a branch above the bifurcation, bilirubin may be normal and an elevated alkaline phosphatase level may be the only abnormality. However, mild accompanying elevations of aspartate aminotransferase and alanine aminotransferase are common.

Scans

Ultrasonography is more sensitive than computed tomography for the identification of dilated bile ducts and may suggest the location of a mass. A computed tomography scan more accurately images a mass and the configuration of the liver, pancreas, and regional lymph nodes. A computed tomography-guided needle biopsy may be diagnostic.

Surgery

In some patients, surgical exploration is the only means of making a diagnosis after suspicion of a gallbladder or bile duct tumor has been raised by the laboratory and imaging studies.

Treatment

The definitive treatment of gallbladder and bile duct cancers is surgical. When gallbladder cancer is found incidentally as a tiny in situ lesion at the time of cholecystectomy for gallstones, the cure rate approaches 100%. On the other hand, when the cancer has invaded the muscle of the gallbladder wall, the 5-year survival is less than 5%, and when the tumor has invaded the liver, virtually no patient survives 5 years.

The prognosis for patients with bile duct cancer is only marginally better. Overall 5-year survival is about 5%, but if the lesion is located in the distal common bile duct, a 25% 5-year survival has been reported after pancreaticoduodenectomy.

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