Diagnosis of HCC
The typical symptoms of HCC include right upper quadrant pain and weight loss in a patient who may be known to have liver disease. However, more recently an increasing number of patients have been diagnosed with HCC when they are asymptomatic through the use of imaging studies in patients at risk and measurement of serum alpha-fetoprotein. However, a definitive diagnosis of HCC usually requires histological examination of tumor tissue. The tumor may be biopsied by one of several means. Simple percutaneous biopsy may be done, particularly in advanced HCC when irregularities may be palpated on the surface of an enlarged liver. More often, a needle biopsy must be done under ultrasound or CT guidance. Occasionally, laparotomy may be necessary to accurately identify and biopsy a mass within the liver. Similarly, laparoscopy may be used although its value is limited because HCC is so often found deep within a cirrhotic liver so that it is not visible from the surface, in contrast to metastatic liver cancer which is readily seen at laparoscopy. The risk of complications, particularly bleeding, following needle biopsy of HCC are greater than when other non-malignant conditions are biopsied presumably because of the vascular nature of the tumor [3]. There are cases reported of HCC spread along track of a needle biopsy, although the frequency of this complication is probably about 1% [4]. Because of concern about the risk of spreading HCC through needle biopsy, there has been some reluctance to require histologic confirmation of HCC before offering treatment to patients, particularly in the case of potentially curative therapies such as resection or transplantation.

For clinical purposes, a typical radiologic appearance with or without a raised serum alpha-fetoprotein may be considered sufficient to allow the patient to be listed for liver transplantation. Similarly, for research purposes, a recent EASL conference listed standard criteria for diagnosis of HCC that do not involve biopsy [5]. Radiologic criteria include two imaging techniques both showing a focal lesion greater than 2 cm in diameter with features of arterial hypervascularization or a single radiologic study with these features combined with a serum alpha-fetoprotein level of greater than 400 ng/ml.

Because current management guidelines for hepatocellular carcinoma (HCC) do not require biopsy to prove the diagnosis, we have evaluated our experience of patients with liver disease and hepatic lesions suspicious for HCC who underwent both fine needle aspiration and core biopsy at Saint Louis University. We correlated the biopsy results with various clinical, biochemical and radiologic features.

HCC was diagnosed by biopsy in 74 (63%) of 118 cases. The use of both FNA and core biopsy increased the diagnostic yield of the procedure from 54% for FNA and 55% for core biopsy individually to 63%. On mean follow up of 27.5 months, an additional 10 patients were found to have HCC while 26 had no further evidence of HCC. Patients with positive biopsy results had significantly higher serum AFP levels (median 57 vs. 12, p=0.014) than those with negative biopsies, although the groups were otherwise comparable with regard to other tests of liver function, tumor diameter and Child-Pugh class.

We compared the diagnosis of HCC from a combination of these biopsies and follow up with standard non-invasive diagnostic criteria advocated by the European Association for the Study of the Liver (EASL). Of 62 patients meeting the non-invasive EASL criteria for HCC, only 50 were found to have HCC on biopsy or follow up. Thus 8 (13%) would have been falsely diagnosed with HCC as follow up data on the remaining 4 patients was incomplete. No patient developed evidence of tumor spread along the needle track after biopsy.

We feel therefore that image-guided biopsy of lesions clinically suspicious for HCC should be routinely performed to allow adequate treatment planning as the risks of biopsy appear small and the potential benefits significant.

Treatment Options for HCC
Treatment options for HCC become fewer as stage of tumor and/or cirrhosis progress. Patients with early HCC and minimal signs of hepatic decompensation (e.g. TNM stage </= T2, Childs-Pugh Class A), are considered for the three potentially curative options of transplantation, surgical resection or local ablation therapies. The choice between these three is controversial and is discussed below. Patients with TNM stage >T2 are generally not considered transplantation candidates. Some may still qualify for surgical resection, while others may be treated with chemoembolization or radiofrequency ablation. Advanced tumor stage in conjunction with advanced cirrhosis (Child-Pugh Class C) limits therapeutic options significantly. Chemotherapy may be given, but its efficacy has been disappointing and rarely curative. Unfortunately, the majority of patients present at these later stages of disease. Indeed, those with poor functional status and advanced disease should probably receive comfort care measure only. The Barcelona-Clinic Liver Cancer Group uses a detailed treatment algorithm driven by stage of tumor, stage of cirrhosis, and functional status [6].

Liver transplantation has recently come to the fore as a favored option for those with early stage HCC. Like local resection and ablation, transplantation offers potential for cure, but also decreases recurrence risk and eliminates other complications of cirrhosis. The increased use of transplantation for HCC comes at a time when there is both an increasing incidence of HCC, but also a persistent shortage of organs. The transplant community continues to grapple with transplantation criteria and prioritization of HCC patients to optimize both efficacy and just allocation of organs. Accurate diagnosis, staging and optimal pre-transplant care are critical components of this ongoing process. Several controversies remain including the roles of living donation, tumor down-staging and rescue transplantation. A working knowledge of the current transplant option and its controversies is essential to those caring for patients with early HCC.

References

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2. El-Serag H. Epidemiology of hepatocellular carcinoma. Clinics in Liver Disease 2001;5:87-107.
   
   
3. McGill D, Rakela J, Zinsmeister A, Ott B. A 21-year experience with major hemorrhage after percutaneous liver biopsy. Gastroenterology 1990;99:1396-1400.
   
   
4. Isobe H, Imari Y, Sakai H, Sakamoto S, Nawata H. Subcutaneous seeding of hepatocellular carcinoma following fine-needle aspiration biopsy. Journal of Clinical Gastroenterology 1993;17:350-352.
   
   
5. Bruix J, Sherman M, Llovet J. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. Journal of Hepatology 2001;35:421-430.
   
   
6. Llovet J, Fuster J, Bruix J. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transplantation 2004;10:S115-120.