Can hepatocellular carcinoma (HCC) produce unconventional metastases? Four cases of extrahepatic HCC.

AIMS AND BACKGROUND: Extrahepatic spread of hepatocellular carcinoma (HCC) diagnosed during the clinical course of the disease is not frequent; however, with the prolonged survival of HCC patients, the incidence of extrahepatic metastases seems to be increasing. METHODS AND STUDY DESIGN: We present four unusual cases of extrahepatic metastasis from HCC: the first concerns a patient who underwent a liver transplantation for HCC with cirrhosis and three years later developed metastases in the lung and the left orbit; the second is that of a patient who developed an extraperitoneal pararectal metastasis; in the third case a large osteolytic lesion developed on the left iliac bone, and in the fourth case we found an isolated metastasis in the left mandible. RESULTS AND CONCLUSIONS: These cases offer important information related to the unusual biology of isolated metastases from HCC after successful treatment of the primary cancer.

Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma.

PURPOSE: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive either 80 IU/m(2) or 160 IU/m(2) of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. RESULTS: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (+/-SE) survival for all subjects was 15.8 months (474 days +/- 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. CONCLUSION: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.