Screening for metastatic malignant melanoma of the uvea revisited.
ABSTRACT The purpose of the current study was to assess the value of routine imaging and liver function tests in detecting metastases from malignant melanoma of the uvea.
Forty-six consecutive patients diagnosed with metastatic uveal melanoma between 1985 and 1996 who had participated in a screening program that included annual liver function tests (LFT), chest X-ray, and abdominal ultrasonography (US) were eligible for this retrospective cohort study. Main outcome measures were the sensitivity of screening tests, presence of symptoms, recurrence free interval, and metastatic burden.
Metastases were diagnosed in 74% of patients (95% confidence interval [95% CI], 59-86) at screening and in 26% (95% CI, 14-41) when the patient consulted a physician because of symptoms that developed before the next scheduled visit. Of all the patients, 59% (95% CI, 43-73) were asymptomatic, and 80% (95% CI, 66-91) had only hepatic metastases. The median recurrence free interval, greatest dimension of the largest metastasis, and metastatic burden of the two groups did not differ. US was diagnostic in 78% (95% CI, 64-89), at least 1 LFT test was abnormal in 70% of patients (95% CI, 54-82), and a chest X-ray was abnormal in 2% of patients (95% CI, 0-12). LFTs and US did not reveal hepatic metastases in 33% and 4% of patients, respectively. The sensitivity of individual LFTs ranged from 0.27 to 0.67, and their specificity from 0.90 to 0.96, with lactate dehydrogenase being the most sensitive LFT used.
The authors believe that annual screening with LFTs and abdominal US will identify 59% of patients while they are still asymptomatic and that semiannual screening will detect >95% of such patients. Chest X-ray has a very low yield and is recommended only at baseline to exclude metastatic disease to the eye and if pulmonary symptoms develop.
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ABSTRACT: About 50% of patients with uveal melanoma (UM) develop metastases during the course of their disease. We analyzed serum levels of Growth Differentiation Factor-15 (GDF-15), with the aim of identifying patients with early metastases. GDF-15 concentration was measured using an enzyme-linked immunosorbent assay (ELISA) in serum samples from 188 UM patients (170 patients without metastases; 18 patients with clinically detectable metastases) and 18 healthy control individuals. Data were analyzed with respect to differences between patients with and without clinically detectable UM metastases. GDF-15 serum levels were further analyzed with regard to significant patient and tumor characteristics as revealed by histology and multiplex ligation-dependent probe amplification (MLPA) to determine chromosome 3 copy number. GDF-15 expression in UM was investigated by immunohistochemistry. Patients with clinically detectable metastases had significantly higher GDF-15 serum levels compared to those without clinically detectable metastases as well as to healthy individuals (ANOVA; p < 0.001). GDF-15 concentrations in UM patients with overt clinically detectable metastases were significantly higher than those in UM patients with a second malignancy in remission but without clinically detected UM metastases (ANOVA; p < 0.001). No association between serum concentration of GDF-15 and clinical, pathological, and genetic features was observed. GDF-15 protein was only expressed in a minority of UM cells in most tumors. Our data suggest that GDF-15 can be used as a serum marker for the diagnosis of metastases in UM patients. Further data collection and analysis are necessary to evaluate a possible prognostic role of GDF-15 in predicting early metastases.Albrecht von Graæes Archiv für Ophthalmologie 09/2011; 250(6):887-95. · 2.17 Impact Factor