Abstract: Toxicity of adjuvant mitotane treatment is poorly known; thus, our aim was to assess prospectively the unwanted effects of adjuvant mitotane treatment and correlate the findings with mitotane concentrations. Seventeen consecutive patients who were treated with mitotane after radical resection of adrenocortical cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory evaluation, monitoring of mitotane concentrations, and a hormonal work-up at baseline and every 3 months till ACC relapse or study end (December 2007). Mitotane toxicity was graded using NCI CTCAE criteria. All biochemical measurements were performed at our center and plasma mitotane was measured by an in-house HPLC assay. All the patients reached mitotane concentrations >14 mg/l and none of them discontinued definitively mitotane for toxicity; 14 patients maintained consistently elevated mitotane concentrations despite tapering of the drug. Side effects occurred in all patients but were manageable with palliative treatment and adjustment of hormone replacement therapy. Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS than aldosterone. Mitotane induced either perturbation of thyroid function mimicking central hypothyroidism or, in male patients, inhibition of testosterone secretion. The discrepancy between salivary and serum cortisol, as well as between total and free testosterone, is due to the mitotane-induced increase in hormone-binding proteins which complicates interpretation of hormone measurements. A low-dose monitored regimen of mitotane is tolerable and able to maintain elevated drug concentrations in the long term. Mitotane exerts a complex effect on the endocrine system that may require multiple hormone replacement therapy.
Abstract: Chromogranin A (CgA) is the neuroendocrine (NE) marker most frequently employed in detecting NE differentiation in prostate cancer patients, either at the tissue level or in the general circulation.
Abstract: Patients with Cushing's syndrome (CS) have a mortality rate four times higher than age- and sex-matched subjects, mainly due to cardiovascular events. Serum osteoprotegerin (OPG) levels are increased in patients with cardiovascular disease and/or excess bone resorption.
Abstract: Oxidized low density lipoproteins (oxLDLs) may exert several pro-inflammatory effects that can contribute to the development of coronary artery disease (CAD). Evaluating a possible correlation between oxLDLs and clinical expression of CAD, we measured specific lipid peroxidation indices in healthy subjects and in patients at different clinical stages of CAD. We observed a slight, but not significant, increase in plasma content of cholesterol oxidation products, i.e. oxysterols, in all CAD patients, and a slight, but not significant, increase of 4-hydroxynonenal-protein adducts only in subjects with acute CAD. Moreover, CAD patients showed a plasma rise of specific inflammatory proteins, i.e. C-reactive protein, intercellular adhesion molecule-1, and interleukin-8, but not of monocyte chemotactic protein-1. These preliminary data, without excluding an involvement of oxidative stress and inflammation in CAD, do not show a strict correlation between relevant plasma markers, other than C-reactive protein, and acute phase of the disease.
Abstract: We evaluated serum homocysteine concentrations and the C677T polymorphism of the gene encoding for methylene tetrahydrofolate reductase, a key enzyme for homocysteine metabolism, in 57 patients with Cushing's syndrome, 41 with active disease, and 16 in remission after successful surgery and 105 blood donors. The patients with active Cushing's syndrome had significantly higher serum homocysteine levels and lower folate concentrations than either the patients in remission or controls. The presence of a statistically significant difference in homocysteine concentrations among the three groups was confirmed after adjustment for confounding variables. In a multiple regression model, homocysteine levels were significantly associated with midnight serum cortisol levels (beta = 0.33, P = 0.01), which is the most sensitive marker of endogenous hypercortisolism, and serum folate levels (beta = -0.32, P = 0.02). The distribution of methylene tetrahydrofolate reductase genotypes was not different between patients and controls. In conclusion, active hypercortisolism is associated with hyperhomocysteinemia and reduced serum folate concentrations, whereas the patients in remission have homocysteine concentrations comparable with healthy subjects. Low serum folate concentrations do not fully account for the increase in homocysteine levels that are positively correlated with cortisol levels. Hyperhomocysteinemia may be key to the prothrombotic state and increased cardiovascular risk of Cushing's syndrome.
Abstract: The authors have previously demonstrated in different experimental models that sustained processes of cellular growth are characterized by alterations of cholesterol metabolism not only in the proliferating tissues but also in the plasma compartment.
Abstract: Carcinoembryonic antigen and CA 19.9 are markers of colorectal neoplasms, often related to tumor burden. Elevated pre-operative levels parallel disease extent and may foresee adverse prognosis. CEA and CA 19.9 may increase post-operatively, indicating tumor recurrence. Only limited data are available on the influence of chemotherapeutic treatments on these two markers, to detect chemotherapy-induced cytolysis. We measured CEA and CA 19.9 before and after a chemotherapy regimen of five days consisting of folinic acid and 5-fluorouracil in forty patients with colorectal cancer. No consistent fluctuation was detected, the examined tumor markers being related in a given patient only to tumor burden.
Abstract: We have evaluated tumor-associated trypsin inhibitor (TATI) as a marker for pancreatic and hepatic cancer. Of the patients studied 52 had pancreatic cancer, 30 primary liver cancer, 32 chronic pancreatitis, 25 biliary tract inflammatory disease, and 28 liver cirrhosis. A considerable number of falsely elevated values were observed in benign biliary diseases and in chronic relapsing pancreatitis. In pancreatic cancer the sensitivity of TATI was 63% while that of CEA was 40% and of CA19-9 77%. TATI is a marker of pancreatic disease but it does not differentiate between pancreatitis and pancreatic cancer. In liver cancer TATI and AFP has similar sensitivity and specificity.
