AJR 2003; 180:441-454
© American Roentgen Ray Society
Imaging in the Diagnosis, Staging, Treatment, and Surveillance of Hepatocellular Carcinoma
Janio Szklaruk1,
Paul M. Silverman and
Chusilp Charnsangavej
1 All authors: Division of Diagnostic Imaging, The University of Texas M. D.
Anderson Cancer Center, 1515 Holcombe Blvd., Box 57, Houston, TX
77030-4009.
Received December 11, 2001;
accepted after revision July 9, 2002.
Address correspondence to J. Szklaruk.
Introduction
Hepatocellular carcinoma is the eighth most common malignancy worldwide.
This article will review the epidemiology, clinical presentation, staging,
pathology, laboratory findings, radiology, and treatment of hepatocellular
carcinoma.
Epidemiology
Hepatocellular carcinoma represents 6% of all cancers and is the most
common primary hepatic malignancy worldwide. A geographic bias is seen, with
an increased incidence of hepatocellular carcinoma in the Far East, Southeast
Asia, and sub-Saharan Africa (90 cases per 100,000 population vs 2.4 cases per
100,000 in the United States)
[1,2,3,4].
The most important risk factors include cirrhosis and hepatitis B and C
viruses. Additional risk factors include hemochromatosis; excessive androgens;
1-antitrypsin deficiency; and exposure to aflotoxins,
thorotrast, oral contraceptives, and vinyl chloride
[4]. The latter is associated
with all types of liver tumors, including angiosarcomas
[5]. Hepatitis B virus is
considered to be the primary cause of 80% of cases worldwide. The peak age of
incidence is 50-70 years, with a male predominance of 4:1. The incidence in
the United States has increased approximately 70% during the past two decades,
from 1.4 per million in 1976-1980 to 2.4 per million in 1991-1995
[6]. Surveillance Epidemiology
and End Results of the National Cancer Institute evaluation of 7389 cases of
hepatocellular carcinoma reported an improvement in the 1-year survival rate
from 14% to 23% during the same periods
[1]. This improvement is
thought to be a reflection of the earlier detection of small resectable
tumors, a more aggressive surgical approach, and the wider availability of
liver transplantation. The 5-year survival rate has increased from 2% to 5%,
and the increase has resulted in a slight change in the still-very-low median
survival rate from 0.57 to 0.64 years.
Clinical Presentation
Clinical manifestations are often masked by the presence of cirrhosis and
or chronic hepatitis. Common symptoms include abdominal pain, malaise,
fatigue, and weight loss (Table
1). The most common finding on physical examination is an
enlarged, irregular, and nodular liver. Jaundice and abnormal findings of
liver function tests may not be present until late in the course of the
disease because of the functional reserve of the liver. A number of
paraneoplastic manifestations of hepatocellular carcinoma, including
hypercalcemia and hyperglycemia, are directly or indirectly a result of tumor
secretion or synthesis [7].
Polycythemia occurs in fewer than 10% of patients.
Staging
The staging of the disease is performed using the TNM system
[8] (Fig.
1A,1B,1C,1D,1E,1F,1G,1H,1I,1J
and Table 2). The primary
lesion is defined by tumor size, the number and location of lesions, invasion
of vascular structures, and biliary extension. In addition, this staging
system addresses the presence and location of regional nodal metastasis and
the presence or absence of distant metastases. The most common sites of
metastatic disease are the lung and bony skeleton. In the latest data analysis
(1985-1996) from the National Cancer Data Base, 4.6% of the patients were
stage I; 13.7%, stage II; 23%, stage III; 33.8%, stage IVA; and 23.9%, stage
IVB [9].
New staging and scoring systems have recently challenged the widely
accepted TNM classification
[10,11,12,13].
The Cancer of the Liver Italian Program has developed a different scoring
system that is based on Child-Pugh classification
[14]. This classification
includes assessment of ascites, encephalopathy grade, albumin level,
prothrombin time, and bilirubin level
[15]. The Cancer of the Liver
Italian Program staging for liver disease includes not only tumor morphology
but also -fetoprotein levels and grading of portal vein invasion (on a
score of 1-6). The Barcelona Clinic Liver Cancer group has also developed a
staging score for hepatocellular carcinoma that includes symptomatology and
vascular and extrahepatic invasion
[13]. The Okuda staging system
(I-III) includes the presence of ascites, jaundice, and serum albumin levels
[16].
The natural progression of hepatocellular carcinoma is well documented
[16]. The overall median
survival of hepatocellular carcinoma patients with no treatment is reported to
be 1.6-4.1 months for stages I and II and 0.8-2.4 months for stages III and IV
[16,
17].
Pathology
The gross pathology of hepatocellular carcinoma is a direct reflection of
the imaging findings. Hepatocellular carcinoma may appear as a unifocal mass,
multifocal nodules of variable size, or diffusely infiltrative. The tumor may
cause liver enlargement, and small nodules or diffuse patterns may be hidden
in a cirrhotic parenchyma. The tumor is paler than normal liver parenchyma and
in well-differentiated cases may have a greenish hue as a result of bile
accumulation.
Microscopically, tumors range from well differentiated to highly anaplastic
[18]. Four histologic
classifications are based on the structural organization: trabecular,
pseudoglandular, compact, and scirrhous, the trabecular pattern being the most
common. The pseudoglandular pattern has malignant hepatocytes surrounding a
lumen that may contain bile, with some of these tumors having clear cells
because of glycogen or fat. Scirrhous, the least common pattern, contains
fibrous stroma separating the tumor cell plates.
The development of hepatocellular carcinoma from premalignant lesions is
reported to occur in stages. The transformation usually begins in a cirrhotic
background, with regenerative nodules evolving into dysplastic nodules, and
the subsequent development of early hepatocellular carcinoma, which, if
untreated, becomes advanced carcinoma.
The fibrolamellar type of hepatocellular carcinoma has distinct clinical,
histologic, and prognostic features and a mean survival of 68 months compared
with conventional hepatocellular carcinoma. The fibrolamellar tumor is more
frequent in young patients who have no history of cirrhosis or chronic liver
disease.
Laboratory Findings
Testing for the -fetoprotein level is the primary laboratory test
for diagnosing hepatocellular carcinoma (sensitivity, 80-70%; specificity,
90%). Values greater than 400 ng/mL are most diagnostic
[19]. Elevated
-fetoprotein levels have also been reported in yolk sac tumors,
cirrhosis, massive liver necrosis, chronic hepatitis, pregnancy, fetal
distress, and fetal neural tube defects. Other tumor markers with less
sensitivity include des-gamma-carboxyprothrombin (sensitivity, 58-91%;
specificity, 84%), -L-fucosidase (sensitivity, 75%; specificity,
70-90%), and isoenzymes of 
-glutamyl transferase (sensitivity, 60%;
specificity, 96%).
Radiology
Radiography of the chest may show pulmonary and skeletal metastases
(Fig. 2). The right
hemidiaphragm is elevated with hepatomegaly
[19].
Sonography has been postulated as a screening imaging modality for
hepatocellular carcinoma in patients with a history of chronic liver disease
(hepatitis or alcohol abuse)
[20]. However, the role of
sonography in screening has yet to be fully determined. The most common
sonographic appearance of small well-differentiated hepatocellular carcinoma
(<3 cm) is a well-circumscribed hypoechoic mass
[20]
(Fig. 3). However, sonography
cannot reliably distinguish hepatocellular carcinoma from other solid lesions
in the liver. The sonographic appearance in larger masses is variable and is
related to the presence of fat, calcium, and necrosis. The presence of compact
cellular elements, necrosis, or sinusoidal dilatation gives a hypoechoic
appearance, whereas the presence of hemorrhage, fatty change, or fibrosis is
seen as a hyperechoic mass. A surrounding capsule, when present, generally
appears hypoechoic (Fig.
4).
View larger version (136K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4. —61-year-old man with metastatic hepatocellular carcinoma.
Transverse sonogram of liver with sonographically guided biopsy shows
hyperechoic mass with hypoechoic capsule (arrow) in right lobe of
liver. Echogenic needle (arrowhead) is visualized.
|
|
Sonography is helpful in providing guidance for percutaneous biopsy and in
delivering therapy for a suspected liver mass
(Fig. 4). Duplex and color
Doppler sonography can show hypervascularity and arteriovenous shunting.
Doppler and power Doppler sonography may play a role in differentiating
hepatocellular carcinoma from other small tumors. Doppler sonography of
hepatic nodules may play a role in selecting a nodule for biopsy in patients
with hepatocellular carcinoma that is suspected as a result of an elevated
-fetoprotein level.
Sonographic contrast agents have shown promise in characterizing masses
suspected to be hepatocellular carcinoma
[21]. A problem exists in
distinguishing regenerative nodules in cirrhosis from hepatocellular
carcinoma. Recently, Fracanzani et al.
[22] evaluated
contrast-enhanced Doppler sonography in distinguishing early hepatocellular
carcinoma from nonmalignant nodules in cirrhosis. Those authors reported
intratumoral arterial blood flow in 95% of hepatocellular carcinomas versus
28% of nonmalignant tumors. Doppler sonography may be a promising imaging
modality for this radiologic problem. In staging, sonography can provide
information regarding the size, number of lesions, and involvement of the
biliary tree, and can help in evaluating the portal vein, hepatic vein, and
inferior vena cava (Fig.
5A,5B).
An intravascular arterial waveform indicates neoplastic rather than bland
thrombus. However, the lack of an arterial waveform does not exclude tumor
thrombosis.
View larger version (147K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5A. —50-year-old man with history of cirrhosis and hepatitis B and
C. Transverse color Doppler sonogram of right upper quadrant shows flow of
middle hepatic vein (white arrow), no flow in right hepatic vein
(arrowhead), and echogenic thrombus in inferior vena cava (black
arrow).
|
|
View larger version (60K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 5B. —50-year-old man with history of cirrhosis and hepatitis B and
C. Transverse color Doppler sonogram of right upper quadrant shows flow in
right main portal vein (arrow). Normal spectral waveform
(arrowhead) is also shown.
|
|
Although many imaging modalities are essential in the diagnosis and staging
of hepatocellular carcinoma, CT is the most commonly used. On unenhanced CT,
hepatocellular carcinoma appears hypodense
(Fig. 6) except in diffusely
fatty liver, where it may appear denser. Hemorrhage or calcifications may be
detected but are rare (5%). Fatty metamorphosis of hepatocellular carcinoma
will appear as areas of low attenuation.
The CT evaluation of the liver in a patient with a clinical suspicion of
hepatocellular carcinoma should be performed at three stages of contrast
enhancement [23,
24]: the hepatic arterial
phase at 20-30 sec after the infusion of contrast material, an early
parenchymal phase at 40-55 sec, and the portal venous phase at 70-80 sec after
the infusion of contrast material. Hypervascular lesions are best viewed
during the earlier phases of enhancement. The rate of injection also plays a
role in the sensitivity of CT to liver lesions; a rate of 4-8 mL/sec is
suggested. The added speed and flexibility of multidetector CT (MDCT) allows
high-quality, thin-section imaging and permits three-dimensional
reconstruction for preoperative vascular mapping.
Hepatocellular carcinoma predominately shows maximum enhancement during the
hepatic arterial phase (Fig.
7A,7B,7C).
In the portal venous phase of enhancement, the tumor will become
hypoattenuating compared with the liver as a result of rapid washout. Although
most lesions have hyperdense components in the early phase, a small percentage
may be isodense or hypodense after the administration of contrast material
[25]. A heterogeneous pattern
of enhancement has been termed the "mosaic" pattern. Heterogeneous
attenuation may often be due to necrosis. When a capsule is present, it is
usually hypodense on the hepatic arterial phase, of mixed density on the
portal venous phase, and showing enhancement on the delayed images. Recent
studies have reported that delayed scans might increase confidence in the
detection of lesions [26]
(Fig.
8A,8B).
View larger version (140K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 7C. —74-year-old man with cirrhosis and history of alcohol
exposure. Contrast-enhanced CT scan of liver during venous delayed phase of
enhancement shows decreased contrast between lesion and liver.
|
|
View larger version (85K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 8B. —Axial CT scans of abdomen in 58-year-old man with hepatitis
B. Image obtained during delayed phase of contrast enhancement shows increase
in contrast (arrow) between low-attenuation hepatocellular carcinoma
and liver parenchyma.
|
|
In CT arterial portography, the portal system is opacified with contrast
material. CT will show relatively low attenuation of the hepatocellular
carcinoma because the blood supply is from the hepatic artery. CT arterial
portography is usually used in patients in whom the clinical suspicion of
hepatocellular carcinoma is high. This technique has been reported to be the
most sensitive technique for the detection of liver tumors, but it is
invasive, requiring catheter insertion
(Fig. 9). Most recently, MDCT
has provided high-quality images and has generally supplanted CT arterial
portography [27].
View larger version (125K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 9. —46-year-old man with hepatitis B. CT angiogram of liver
during portal phase after direct infusion of contrast material into superior
mesenteric artery shows low-attenuation hepatoma (white arrow).
Spleen (black arrow) is also low in attenuation with respect to
liver.
|
|
CT is highly accurate in staging hepatocellular carcinoma by detecting the
number of lesions and segments, regional adenopathy, vascular tumor invasion
(Fig. 10), and metastases
[25,
28]. Distinction between bland
thrombus and tumor thrombus is not always possible, but the identification of
thrombus enhancement is indicative of tumor (Fig.
11A,11B).
Indirect signs of a portal vein diameter greater than 23 mm
(Fig. 12) have been reported
to have a low (62%) sensitivity but 100% specificity for tumor thrombus
[29]. Bile duct obstruction is
usually related to extrinsic compression on the biliary system by the tumor or
direct tumor extension into the biliary system. CT also plays a major role in
posttreatment evaluation and surveillance
(Fig. 13), guidance for biopsy
of suspected recurrences, assessing regeneration of liver parenchyma (Fig.
14A,14B),
and follow-up after ablation when a change in enhancement suggests tumor
recurrence. CT is somewhat limited in assessing peritoneal implants because of
the presence of ascites related to the primary hepatic disease.
View larger version (132K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 10. —50-year-old man with history of hepatitis B and C, cirrhosis,
and portal hypertension. Delayed phase contrast-enhanced CT scan of liver
shows thrombus (white arrow) in proximal inferior vena cava. Primary
tumor (black arrow) is in segment VIII.
|
|
View larger version (136K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 12. —51-year-old man with history of hepatitis C, cirrhosis, and
hemochromatosis. Delayed phase contrast-enhanced CT scan of abdomen shows
filling defect (arrow) in main portal vein. Note nodular contour of
liver that is consistent with cirrhosis.
|
|
View larger version (157K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 14A. —50-year-old man with history of hepatitis B and C and
cirrhosis. Patient also had history of solid mass in lateral segment of left
lobe of liver. Delayed phase contrast-enhanced CT scans of abdomen obtained 5
days (A) and 5 months (B) after radiofrequency ablation. Both
images show change in size and attenuation of treated area (arrows)
in lateral segment of left lobe of liver.
|
|
View larger version (147K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 14B. —50-year-old man with history of hepatitis B and C and
cirrhosis. Patient also had history of solid mass in lateral segment of left
lobe of liver. Delayed phase contrast-enhanced CT scans of abdomen obtained 5
days (A) and 5 months (B) after radiofrequency ablation. Both
images show change in size and attenuation of treated area (arrows)
in lateral segment of left lobe of liver.
|
|
MR imaging should include T1-weighted images, T2-weighted images with fat
suppression, and dynamic contrast-enhanced gradient-echo sequences of the
liver. The T1 technique is usually a breath-hold gradient-echo sequence with
an in-phase TE of 4.1 msec at 1.5-T field-strength magnet. The T2-weighted
sequences are obtained at two TE ranges (60-70 and 136-150 msec) for lesion
characterization. For T2-weighted sequences, a fast spin-echo sequence with
fat suppression is performed. The critical sequences in the detection of
hepatocellular carcinoma are the dynamic gadolinium-enhanced images
[24,
30]. The arterial phase of
enhancement may be the only phase in which a tumor may be revealed (Fig.
15A,15B).
On T1-weighted sequences, hepatocellular carcinoma is usually hypointense to
liver (Fig.
16A,16B,16C).
Areas of increased intensity may be due to fat, protein, or copper in the
tumor [31]. On T2-weighted
sequences, the tumor is usually hyperintense to liver
[32] (Fig.
16A,16B,16C).
Dynamic enhancement shows hyperintensity on the hepatic arterial phase because
of the hepatic artery supply
[33,
34]. The fibrous capsule shows
low signal intensity on T1- and T2-weighted images and enhancement on delayed
contrast-enhanced images (Fig.
17A,17B).
The tumor may invade the portal vein, hepatic veins, or the biliary system
(Figs. 18 and
19). The MR imaging biliary
contrast agent, mangafodipir (Teslascan; Nycomed-Amersham, Oslo, Norway) is
taken up by hepatocytes and well-differentiated tumors (Fig.
16A,16B,16C).
This technique can reveal lesions not visualized on the unenhanced images
[35]. MR imaging plays a role
in postoperative treatment. Tumor may recur locally or distant from the
surgical site. After successful ablation, patients with hepatocellular
carcinoma show low-signal-intensity areas on the T2-weighted protocol.
View larger version (149K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 15A. —52-year-old man with history of hepatitis B and C. Axial
two-dimensional spoiled gradient-echo unenhanced MR image (TR/TE, 4.1/110)
shows faint hyperdense nodules (arrow) in right lobe of liver.
|
|
View larger version (142K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 16A. —74-year-old man with history of alcohol exposure. Axial
spin-echo T1-weighted MR image of liver (TR/TE, 600/8) without IV contrast
material shows low-signal-intensity mass (arrow) in segment V of
liver.
|
|
View larger version (135K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 16C. —74-year-old man with history of alcohol exposure. Axial
spin-echo T1-weighted MR image of liver (600/8) after administration of
mangafodipir (Teslascan; Nycomed-Amersham, Oslo, Norway) shows uptake of
contrast material, which suggests moderately to well-differentiated tumor
(arrow).
|
|
View larger version (146K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 17A. —73-year-old man with hepatitis C and cirrhosis. Axial fast
spin-echo T2-weighted MR image (TR/TE, 136/68; echo-train length, 12) of liver
shows tumor to be slightly hyperintense. Note thin low-signal-intensity
capsule (arrow).
|
|
View larger version (134K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 17B. —73-year-old man with hepatitis C and cirrhosis. Delayed
fat-saturated gadolinium-enhanced axial spin-echo T1-weighted MR image (TR/TE,
600/9) shows that hepatocellular carcinoma has low signal relative to liver.
Note enhancing capsule (arrow).
|
|
View larger version (117K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 18. —72-year-old man with history of hepatitis C and cirrhosis.
Axial gradient-echo MR image (TR/TE, 110/4.1) during venous phase of
enhancement after dynamic administration of gadolinium shows filling defect
(arrow) in main left portal vein.
|
|
View larger version (133K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 19. —61-year-old man with history of hepatitis B and cirrhosis.
Axial time-of-flight gradient-echo MR image (TR/TE, 50/4) of liver during
arterial phase of contrast enhancement shows filling defect (arrow)
in inferior vena cava.
|
|
Various groups have compared the sensitivity of imaging modalities for the
diagnosis and detection of hepatocellular carcinoma
(Table 3). Although the imaging
modalities are similar, direct comparison is limited because the sensitivity
of detection depends on equipment, operator skill, and techniques.
View this table:
[in this window]
[in a new window]
|
TABLE 3 Comparison in Radiology Literature of Sensitivities of CT, Sonography,
and MR Imaging in Diagnosing and Detecting Hepatocellular Carcinoma
|
|
Angiography is a versatile technology that plays a role in the diagnosis
when coupled with CT arterial portography, pretreatment imaging, and treatment
of hepatocellular carcinoma. Angiography plays a role in the pretreatment of
patients with hepatocellular carcinoma with preoperative portal vein
embolization, which can improve the prognosis after right hepatectomy by the
development of compensatory liver hypertrophy
[36] (Fig.
20A,20B,20C).
The hypertrophy may be adequate at 2-4 weeks after portal vein embolization
[36]. Two major approaches to
portal vein embolization are used: direct ileocolic vein catheterization
(requiring laparotomy) and the percutaneous approach. Embolization agents
include Gelfoam (Upjohn, Kalamazoo, MI), coils, thrombin, cyanoacrylate,
polyvinyl alcohol, microspheres, and absolute alcohol. No specific agent has
been shown to be superior. Portal vein embolization is used when the remnant
liver volume is 25% or less of the total liver volume in patients without
compromised liver function. In patients with compromised liver function,
portal vein embolization is used when the volume is 40% or less.
View larger version (133K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 20A. —61-year-old man with serology findings negative for hepatitis
B or C and no history of alcohol abuse. Arterial phase contrast-enhanced CT
scan shows mass (arrow) in liver segment VII.
|
|
View larger version (134K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 20B. —61-year-old man with serology findings negative for hepatitis
B or C and no history of alcohol abuse. Delayed phase contrast-enhanced CT
scans show coils (arrow, B) used in portal vein embolization
(B), hypertrophy (arrow, C) of left lobe of liver, and
changes after trisegmentectomy (C).
|
|
View larger version (116K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 20C. —61-year-old man with serology findings negative for hepatitis
B or C and no history of alcohol abuse. Delayed phase contrast-enhanced CT
scans show coils (arrow, B) used in portal vein embolization
(B), hypertrophy (arrow, C) of left lobe of liver, and
changes after trisegmentectomy (C).
|
|
Angiography also plays an essential role in transarterial catheter
embolization, which is a selective catheterization of the branch of the
hepatic artery feeding the tumor (Fig.
21).
View larger version (108K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 21. —61-year-old man with history of alcohol liver cirrhosis.
Selected image from digital subtraction angiography of right hepatic artery
(white arrow) shows catheter (black arrow) used for
transarterial chemoembolization of tumor (arrowhead) in right lobe of
liver.
|
|
Treatment
The treatment of hepatocellular carcinoma includes surgery, chemotherapy,
radiation, and combination therapies. In the period 1995-1996, the National
Cancer Data Bank reported that 17.7% of patients were treated with
chemotherapy alone, 17% with surgery alone, and 3.2% with radiation therapy
[9,
37].
Surgery is considered the best treatment option. Patients are surgical
candidates if their disease is stage I, II, or IIIA. Surgical removal may be
performed by either tumor resection or orthotopic liver transplantation
[38,
39]. The reported 5-year
survival rate of patients after orthotopic liver transplantation ranges from
58% to 75% [38]
(Table 4). The results in
Table 4 are from a highly
selected population. For resection, the 5-year survival rate ranges from 35%
to 51% (Table 4). The
recurrence rate after resection in one series was reported to be as high as
33%, with a recurrence rate of 3-17% for orthotopic liver transplantation
[40]. Factors considered in
the selection of candidates for surgery are liver function, bilobar disease,
biliary obstruction, venous tumor extension, nodal involvement, and
metastasis.
The 5-year survival rate of unifocal tumors smaller than 5 cm was reported
in one series to be 63% [41].
That report noted that larger tumors were associated with indicators of poor
outcome such as absence of capsule, multiple nodules, satellite nodules, and
vascular invasion.
Percutaneous ethanol injection, transarterial catheter embolization,
cryoablation, and radiofrequency ablation are secondary treatment options for
hepatocellular carcinoma
[42,43,44].
Percutaneous ethanol injection for tumor ablation has been reported to be the
most effective form of direct ablation for hepatocellular carcinoma in lesions
smaller than 3 cm and fewer than three in number (5-year survival rate,
36-68%). Percutaneous ethanol injection is contraindicated in the presence of
gross ascites, bleeding, or obstructive jaundice. Radiofrequency ablation is a
therapeutic option for hepatocellular carcinoma for tumors smaller than 3 cm
and has a 5-year survival rate of 45%. In comparison with percutaneous ethanol
injection, radiofrequency ablation achieved tumor necrosis in fewer sessions
[45]. Cryotherapy is an
alternative treatment for solitary tumors of 3-6 cm. The 5-year survival rate
is 20%. Cryotherapy is contraindicated for lesions near major vessels.
Transarterial catheter embolization uses combination agents to compromise the
flow of the hepatic artery. The agents include gelatin (Gelfoam), iodized oil
(Lipiodol [Guerbet, Aulnay-sous-Bois, France]), and a cytotoxic agent.
Retreatment can be performed in 6-12 weeks. The 5-year survival rate is
reported to be 6-22% (Table 4).
The selective nature of hepatic artery infusion of chemotherapy minimizes
adverse effects while maximizing drug delivery to the tumor. A hepatic artery
infusion pump may be implanted in a selected number of patients. Agents used
include 5-fluorouracil, floxuridine, doxorubicin, mithoxantrone, epirubicin,
and cisplatin [43].
Radiotherapy is a well-documented treatment, and proton therapy has recently
been implemented [46].
Systemic chemotherapy has been used with single and multiple agents
including 5-fluorouracil, interferon, cisplatin, thalidomide, octreotide, and
tamoxifen [43,
47].
Summary
Hepatocellular carcinoma is one of the most common malignancies worldwide.
Imaging plays an essential role in the detection, diagnosis, staging,
treatment, and surveillance of these patients. Reports to clinicians should
include all pertinent diagnostic information for staging, including lesion
size, number, location, and the presence of adenopathy, ascites, cirrhosis,
vascular involvement, biliary tree involvement, and metastases. Despite
advanced imaging techniques and the large number of therapeutic options, the
5-year survival rate remains dismal. Close surveillance with imaging now
affords the opportunity to diagnose recurrences early and to apply the most
effective therapy.
References
- El-Serag HB, Mason AC. Risk factors for the rising rates of primary
liver cancer in the United States. Arch Intern Med
2000;160:3227
-3230[Abstract/Free Full Text]
- El-Serag HB. Epidemiology of hepatocellular carcinoma.
Clin Liver Dis
2001;5:87
-107[Medline]
- Yu MW, Chang HC, Liaw YF, et al. Familial risk of hepatocellular
carcinoma among chronic hepatitis B carriers and their relatives. J
Natl Cancer Inst
2000;92:1159
-1164[Abstract/Free Full Text]
- Tabor E. Hepatocellular carcinoma: global epidemiology.
Dig Liver Dis
2001;33:115
-117[Medline]
- Ward E, Boffetta P, Andersen A, et al. Update of the follow-up of
mortality and cancer incidence among European workers employed in the vinyl
chloride industry. Epidemiology
2001;12:710
-718[Medline]
- El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma
in the United States. N Engl J Med
1999;340:745
-750[Abstract/Free Full Text]
- Luo JC, Hwang SJ, Wu JC, et al. Paraneoplastic syndromes in
patients with hepatocellular carcinoma in Taiwan.
Cancer
1999;86:799
-804[Medline]
- Baron R. Primary tumours of the liver and bile ducts. In: Hubbard
JES, Reznek RH, eds. Imaging in oncology, vol.1
, 1st ed. St. Louis: Mosby-Year Book,
1998: 169-177
- Cance WG, Stewart AK, Menck HR. The National Cancer Data Base
Report on treatment patterns for hepatocellular carcinomas: improved survival
of surgically resected patients, 1985-1996. Cancer
2000;88:912
-920[Medline]
- Chiappa A, Zbar AP, Podda M, et al. Prognostic value of the
modified TNM (Izumi) classification of hepatocellular carcinoma in 53
cirrhotic patients undergoing resection.
Hepatogastroenterology
2001;48:229
-234[Medline]
- Marsh JW, Dvorchik I, Bonham CA, Iwatsuki S. Is the pathologic TNM
staging system for patients with hepatoma predictive of outcome?
Cancer
2000;88:538
-543[Medline]
- Llovet JM, Bruix J. Prospective validation of the Cancer of the
Liver Italian Program (CLIP) score: a new prognostic system for patients with
cirrhosis and hepatocellular carcinoma. Hepatology
2000;32:679
-680[Medline]
- Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma:
the BCLC staging classification. Semin Liver Dis
1999;19:329
-338[Medline]
- The Cancer of the Liver Italian Program (CLIP) investigators.
Prospective validation of the CLIP score: a new prognostic system for patients
with cirrhosis and hepatocellular carcinoma.
Hepatology
2000;31:840
-845[Medline]
- Kim WR, Poterucha JJ, Wiesner RH, et al. The relative role of the
Child-Pugh classification and the Mayo natural history model in the assessment
of survival in patients with primary sclerosing cholangitis.
Hepatology
1999;29:1643
-1648[Medline]
- Okuda K, Ohtsuki T, Obata H, et al. Natural history of
hepatocellular carcinoma and prognosis in relation to treatment: study of 850
patients. Cancer
1985;56:918
-928[Medline]
- Pawarode A, Voravud N, Sriuranpong V, Kullavanijaya P, Patt YZ.
Natural history of untreated primary hepatocellular carcinoma: a retrospective
study of 157 patients. Am J Clin Oncol
1998;21:386
-391[Medline]
- Noltenius H. Hepatocellular carcinoma. In: Noltenius H, ed.
Human oncology: pathology and clinical
characteristics. Baltimore: Urban & Schwarzenberg,
1988: 373-375
- Feldman M. Gastrointestinal disease. In: Sleisenger MH, Feldman M,
Scharnschmidt BF, eds. Sleisenger and Fordtran's gastrointestinal
and liver disease: pathophysiology, diagnosis, management, 6th
ed. Philadelphia: Saunders, 1998;2046
-2050
- Monzawa S, Omata K, Shimazu N, Yagawa A, Hosoda K, Araki T.
Well-differentiated hepatocellular carcinoma: findings of US, CT, and MR
imaging. Abdom Imaging
1999;24:392
-397[Medline]
- Kim AY, Choi BI, Kim TK, et al. Hepatocellular carcinoma: power
Doppler US with a contrast agent—preliminary results.
Radiology
1998;209:135
-140[Abstract/Free Full Text]
- Fracanzani AL, Burdick L, Borzio M, et al. Contrast-enhanced
Doppler ultrasonography in the diagnosis of hepatocellular carcinoma and
premalignant lesions in patients with cirrhosis.
Hepatology
2001;34:1109
-1112[Medline]
- Kim T, Murakami T, Oi H, et al. Detection of hypervascular
hepatocellular carcinoma by dynamic MRI and dynamic spiral CT. J
Comput Assist Tomogr
1995;19:948
-954[Medline]
- Kanematsu M, Oliver JH 3rd, Carr B, Baron RL. Hepatocellular
carcinoma: the
Top
Introduction
Epidemiology
2 cm without (stage T1) (A) and with (stage T2a) (B)
vascular invasion.
