Management of Primary and Metastatic Tumors to the Liver

Introduction

Primary and metastatic tumors to the liver continue to be an important health problem in the United States. Hepatocellular cancer is one of the most common and most malignant tumors occurring in males; in some areas of Asia and Africa, incidence of this cancer continues to increase. Hepatocellular carcinoma varies in incidence from 30 per 100,000 population per year in high-risk regions, such as Asia and Africa, to less than 3 per 100,000 population per year in low-risk regions, such as northern Europe and North America [1]. In 1995, the estimated incidence of primary liver and biliary cancers was 18,500 cases in the United States, with 7,800 estimated deaths from these cancers.

Metastatic neoplasms are much more common and represent the most common malignant tumor of the liver. The relative proportion of primary to secondary neoplasms is estimated to be 1:20. The incidence of primary colorectal cancer, the most common cancer metastasizing to the liver, is estimated to be 138,200, with 55,300 deaths [2]. It is expected that as many as 25% of patients with colorectal cancer will have liver metastases at presentation and 50% will have liver metastases develop metachronously. About 20% of patients, or 27,640, will present with or eventually develop metastatic disease confined to the liver [3].

A common feature in patients with hepatocellular cancer is the presence of cirrhosis. The risk of developing hepatocellular carcinoma is approximately 10% in patients with nutritional cirrhosis (micronodular), 20% in patients with cirrhosis secondary to hepatitis B, 13% in those with hemochromatosis, and 40% in those with alpha-1-antitrypsin deficiency [1].

Although surgical resection is the treatment of choice for hepatocellular carcinoma and, along with transplantation, offers the only chance for cure, resection is not indicated in 70% to 90% of cases. Three conditions preclude liver resection: an unacceptable risk based on the degree of cirrhosis, evidence of extrahepatic disease, and tumor spread within the liver that prevents the attainment of clear surgical margins. Surgical resection in the presence of hepatic cirrhosis is associated with higher intraoperative morbidity and mortality. The presence of compromised liver function, thrombocytopenia, and coagulopathy with increased intraoperative blood loss can lead to postoperative hepatic decompensation and failure. Operative mortality is less than 3% for noncirrhotic patients, as compared with 7% to 25% for cirrhotic patients [1].

Other rare primary tumors also are seen in the liver. Intrahepatic cholangiocarcinomas represent less than 0.5% of liver tumors. These diffuse tumors are rarely detected early enough, and resection usually is not possible. Thus, prognosis is poor.

Surgical resection also is the only potential curative treatment for metastatic cancer to the liver. Without surgery, the median survival of patients with metastatic colorectal cancer confined to the liver is measured in months, with the majority of patients dying within a year (Table 1) [4-11].

Patients with liver metastases from other solid tumors also are candidates for resection. Patients with Wilms' tumor are excellent candidates for resection of hepatic metastases, as are those with a solitary liver metastasis from renal cell carcinoma. Hepatic metastases from other tumors, such as melanoma and gastric, pancreatic, lung, and breast cancer, do not appear to benefit from such efforts.

Liver metastases from endocrine tumors rarely present with localized disease that can be completely resected, but if localized, surgical resection is the treatment of choice. In this group of patients, surgical debulking can be used in those in whom symptoms cannot be controlled by medical treatment and are incapacitating. Patients with endocrine tumors have a long median survival even in the presence of metastatic disease [12].

In this article, we will discuss the present management of patients with primary and metastatic liver tumors, focusing on the currently available imaging techniques and new treatment modalities.

Preoperative Evaluation

The initial diagnosis of a liver tumor can be suggested by symptoms, findings on physical examination, or elevation of a tumor marker, such as carcinoembryonic antigen (CEA) in a patient with a previous history of colorectal cancer, alpha-fetoprotein (AFP) in a patient with hepatocellular carcinoma, or 5-hydroxyindoleacetic acid (5-HIAA) in a patient with a carcinoid tumor. A complete physical examination is mandatory to assess the patient's overall performance status and to look for potential sites of metastases (eg, cervical or inguinal lymph node metastases) that will render the use of any other diagnostic tests unnecessary.

After the diagnosis has been made, a careful preoperative evaluation is crucial to avoid unnecessary surgical explorations that considerably reduce the quality of the short remaining life span of patients with unresectable liver tumors. Only 3% to 30% of patients with hepatocellular carcinoma have disease that can be completely resected [13]. For colorectal cancer, the fraction of patients who may benefit from hepatic resection at some time in the disease process has been estimated to be 5% to 10% [14,15].

Role of Imaging Techniques

Imaging techniques play a major role in the preoperative assessment of patients with hepatic tumors. These imaging techniques help select patients who are candidates for an aggressive surgical approach and help exclude those who present with diffuse liver involvement, unresectable disease because of location (confluence of hepatic veins, hilum of liver with involvement of the main portal vein), and extrahepatic metastases. Although the segmental location is not the sole criterion for determining resectability, such knowledge is useful for planning the type of resection.

Cross-sectional imaging techniques that are used in the selection of candidates for hepatic resection include computed tomography (CT), dynamic CT arterial portography (CTAP), magnetic resonance imaging (MRI), spiral CT (SCT), ultrasound (US), and intraoperative ultrasound (IOUS). All of these technologies have limitations. The surgeon needs to be aware of these drawbacks in order to provide good care. Also, imaging technologies need to be applied in an orderly manner to avoid unnecessary and discouraging surgical explorations, while also keeping cost as low as possible. Lastly, the sensitivity and specificity of the tests used should be high so that patients are not denied potentially curative surgery based on a false result.

The ability to accurately image liver lesions has been limited. In a recent study, among patients considered resectable on the basis of careful preoperative evaluation that included intravenous contrast CT and CTAP, 29% were found to be unresectable at the time of intraoperative staging. Of these, 19.8% had extrahepatic disease and 9.2% had unresectable liver disease. Of the patients with extrahepatic disease, 9.2% had peritoneal implants and 10.6%, periportal lymph node metastases [3].

CT of the abdomen and pelvis has been the imaging modality most frequently used to help define the extent of liver disease. However the sensitivity of the CT scan for detecting liver lesions is rather low, varying from 52% to 85%; in the majority of reports, the sensitivity of this technique is close to 60% (Table 2) [16-27]. The sensitivity of CT for detecting tumor in other areas of the abdomen and pelvis drops significantly, to 27% for the extrahepatic abdomen and 22% for the pelvis. In a study by Sardi et al in which the extent of disease was documented by laparotomy in every instance, the overall sensitivity of abdominal CT was only 41%. In 5 of 15 patients with liver metastases and with true-positive results, the CT scan underestimated the extent of disease [19]. In another study, the sensitivity of abdominal CT was 85%, but the false-positive rate was high (45%) [17]. Problems in differentiating recurrent tumor from postoperative and post-radiation changes on the CT scan may account for the false-positive results seen with this technique. Consequently, CT has a number of disadvantages: It is unable to detect an intra-abdominal recurrence in approximately half of patients. Also, in patients with positive results, it fails to satisfactorily show the extent of disease. Of patients thought to have resectable disease based on CT evidence alone, 25% to 60% were found to have unresectable tumors at laparotomy [3,28,29].

It should be mentioned that routine CT is not indicated for the follow-up of patients after primary resection of colorectal cancer. Rather, CT should be performed after recurrence disease is suggested by symptoms, elevation of a CEA, or findings on physical examination, to try to identify sites of recurrence. This policy is supported by studies in which routine CT was shown to be of little value, even when scans were done as frequently as three times yearly [17].