Diagnosis and Staging

HCC is usually diagnosed at a late stage, with many patients presenting with upper abdominal pain, weight loss, ascites, and other sequelae of portal hypertension. An elevated a-fetoprotein (AFP), especially greater than 400 ng/mL, should raise one's suspicions for HCC, although patients with small tumors may have normal levels. In addition to its diagnostic use, AFP measurements are also used to monitor for tumor recurrence because levels should fall to normal after curative resection. Radiologic confirmation of a liver mass is usually initially made with either ultrasono-graphy (US) or computed tomography (CT). Although US is used as a screening tool, all patients presenting to the University of Texas M. D. Anderson Cancer Center for examination of HCC undergo a three-phase helical CT scan. The early arterial phase is especially useful in imaging hypervascular tumors such as HCC. Although histo-logic diagnosis can be obtained by CT or US-guided percutaneous needle biopsy, we do not recommend that this be performed routinely. Most often the diagnosis of HCC can be obtained based on the patient's history, physical presentation, laboratory findings, and radiologic examinations. If the lesion is deemed to be unresectable and an alternative therapy is being planned, a liver biopsy to document the diagnosis may be warranted.

Several clinical staging systems that rely on liver function parameters are often used to guide initial therapy in patients with HCC. The Okuda staging system, which accounts for both liver function and tumor extension, has traditionally been used for predicting the prognosis of patients with cirrhosis and HCC. A new prognostic score proposed by the Cancer of the Liver Italian Program (CLIP) group (2000) includes Child-Pugh stage, tumor morphology and extension, the presence of portal vein thrombosis, and the serum level of AFP. Compared with the Okuda score, the CLIP score has been shown to give more accurate prognostic information, to be statistically more efficient, and to have a greater survival predictive power.

Whereas clinical staging systems are used for patients with advanced-stage HCC, the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system has been used for accurate prognostic assessment after resection. The AJCC/UICC staging system uses a tumor-node-metastasis (TNM) classification scheme to stratify patients with respect to predicted survival after resection (Table 128-1). In the latest edition of the AJCC staging manual, the tumor categories have been redefined and simplified. All solitary tumors without vascular invasion, regardless of size, are classified as T1 because of similar prognosis. One of the most important changes from the previous AJCC/UICC TNM staging

TABLE 128-1. New AJCC/UICC Tumor-Node-Metastasis, Histologic Grade, and Fibrosis Score Classification Scheme for Hepatocellular Cancer

Primary tumor (T)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Solitary tumor without vascular invasion

T2 Solitary tumor with vascular invasion or multiple tumors, none more than 5 cm T3 Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s) T4 Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Regional lymph node metastasis

Distant metastasis (M) MX Distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis Stage grouping

I T1 N0 M0

II T2 N0 M0 IIIA T3 N0 M0 IIIB T4 N0 M0 IIIC Any T N1 M0 IV Any T Any N M1

Histologic grade (G)

GX Grade cannot be assessed

G1 Well differentiated

G2 Moderately differentiated

G3 Poorly differentiated

G4 Undifferentiated

Fibrosis score (F)

F0 Fibrosis score 0 to 4 (no fibrosis to moderate fibrosis)

F1 Fibrosis score 5 to 6 (severe fibrosis to cirrhosis)

AJCC/UICC = American Joint Committee on Cancer/International Union Against Cancer.

is that the cutoff value for tumor size in the prognostic classification was shifted from 2 to 5 cm, and the influence of tumor size was limited only to patients with multiple tumors. All solitary tumors with vascular invasion, regardless of size, are combined with multiple tumors < 5 cm and are classified as T2 because of similar prognosis. Multiple tumors > 5 cm and tumors with evidence of major vascular invasion are combined and classified as T3 because of a similar poor prognosis. T4 tumors are classified as those with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. Another important feature of the new AJCC/UICC TNM staging is the provision of a separate reporting of fibrosis in every resected case of HCC. The fibrosis scoring system proposed by Ishak and colleagues (1995) has been incorporated into the most recent AJCC/UICC staging system (Ishak 0 to 2, no or minimal fibrosis; Ishak 3 to 4, incomplete bridging fibrosis; Ishak 5 to 6, complete fibrosis and nodules). Patients with severe fibrosis or cirrhosis (Ishak score of 5 to 6) are staged as F1, whereas those patients with no or moderate fibrosis (Ishak score 0 to 4) are staged as F0. The new scoring of severity of fibrosis provides a more precise method to evaluate the impact of fibrosis and cirrhosis on prognosis and should enhance the prognostic value of the new TNM staging system.

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