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Management of Primary and Metastatic Tumors to the Liver

Management of Primary and Metastatic Tumors to the Liver

ABSTRACT: Primary and metastatic liver tumors continue to be a significant health problem in the United States. Hepatic resection or, in selected cases, transplantation are the only curative therapies for patients with resectable disease confined to the liver. Careful preoperative selection is crucial to avoid unnecessary surgical explorations that considerably reduce the quality of the short remaining life of patients with unresectable tumors. The surgeon needs to understand the role of imaging techniques in the evaluation of hepatic tumors for better selection of the patients who are candidates for an aggressive surgical approach. Several other therapeutic options are available for patients with unresectable disease. Until further research delineates the specific interactions among environmental factors, hepatic injury, hepatic regeneration, host factors, and molecular mechanisms of malignant transformation that can lead to specific preventive and treatment interventions, control of this disease will continue to rely on modifications of currently available treatment modalities. [ONCOLOGY 10(6):911-930, 1996]


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

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


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