Trends in Liver Function Tests: A Comparison with Serum Tumor Markers in Metastatic Uveal Melanoma (Part 2) Academic Article uri icon

abstract

  • Aim: To compare trends in liver function test (LFT) levels over consecutive visits before detection of liver metastasis (LM) from uveal melanoma (UM) with such trends in the serum tumor markers S-100β, melanoma inhibitory activity (MIA), osteopontin (OPN), and tissue polypeptide- specific antigen (TPS). Patients and Methods: Blood was drawn from 32 patients with metastatic UM and 43 disease-free (DF) patients semi- annually for levels of S-100β, MIA, OPN, and TPS. Abdominal ultrasonography (US) and LFTs were used to detect LM. Median LFT levels were calculated at 6-month intervals prior to the clinical detection of LM. Trends in LFT levels over consecutive visits in the groups were compared with trends in the tumor markers for these groups. Results: Only LDH gave a statistically significant difference between the trends of the metastasis and DF groups (p=0.0041). When calculating the lead time, all of the elevations were non-significant except for gamma glutamyltransferase which showed a statistically significant elevation at time 0, the time of detection of metastasis. LDH showed a rise at 0-6 months before detection, but this was not significant. For the tumor markers, steeper trendlines were shown for the metastasis group for MIA and S-100β, and most of the markers showed a lead time of more than six months, although this was statistically significant only for OPN. Conclusion: Following the dynamics of tumor markers and LFTs may help to find metastatic disease in UM patients before the metastases are detectable by imaging, enabling earlier treatment. Uveal melanoma (UM) is the most common primary intraocular malignancy in adults (1). Its incidence is 5-7 cases per million per year (2). The 5- and 10-year metastasis rates reach 25% and 34%, respectively (3). The liver is the most common site of metastasis from UM (4). The mortality from metastatic UM has been shown to be 10% at 5 years, and 18% at 10 years (5). The median time from diagnosis of liver metastasis to death is 6-12 months (2). Early diagnosis of metastasis from UM is of great importance due to the treatment options available today, which for liver metastases include systemic or intra-arterial chemotherapy, hepatic artery chemoembolization, immuno- therapy, and resection (6-8). The current most effective option prolonging survival for patients with metastatic UM is surgical resection of metastases and the combination of resection with intra-arterial hepatic chemotherapy (6-8). Our group has recently shown that the median survival time from the detection of metastasis was 3.7-fold higher in patients with metastatic UM who underwent resection of liver metastasis than in the non-operated patients (8). With the current screening methods using abdominal ultrasonography and liver function tests, most metastatic disease is discovered at too late a stage when the liver metastasis are already widespread, and treatment is thus restricted (6, 7). Liver function tests (LFTs), including those for alkaline phosphatase (ALK-P), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), and total bilirubin (TBil) are used routinely in screening for metastasis of UM (9-12). This is possible because UM mostly metastasizes primarily to the liver (13). Our group has shown that there are trends for increasing levels of these LFTs in patients with metastatic disease, with levels rising at least 6 months before clinical detection of metastasis (10). The levels of AST and LDH were predictive of metastatic disease even within

publication date

  • January 1, 2011