Differentiation between benign and malignant tumors of the adrenal cortex was studied by means of seven histologic parameters. Each separate criterion was significantly different in two groups, one consisting of patients without metastases within 10 years after operation and one of patients with metastatic tumors. Discrimination on the basis of single parameters in individual patients, however, was of little value. When a histologic index was calculated using the same parameters but after “weighing,” a much better discrimination was obtained. The histologic index and, to a lesser degree, the mitotic activity seems to be related to the survival time of the patients with adrenal cortical carcinoma. The authors conclude that the calculation of a histologic index based on a summation of different parameters makes it possible to differentiate between malignant and benign adrenal cortical tumors. As single parameters, tumor weight and mitotic activity have the highest discriminating value.
Plasma levels of o,p'-DDD were measured after ingestion of a single oral dose. At the onset of therapy o,p'-DDD was administered as commercially available tablets and granules and in milk, chocolate, and an oil emulsion to 9, 12, 14, 10, and 6 patients, respectively. Following administration in chocolate, emulsion, and milk significantly higher mean plasma levels were recorded in the first 5- and 10-h periods than after tablets. Granules gave significantly lower plasma levels than all other forms. Plasma levels were also measured during maintenance therapy, when a total of 200 g o,p'-DDD was administered to 22 patients with adrenocortical carcinoma. The plasma disappearance rate after termination of long-term therapy was found to be between 18 and 159 days. The recovery of o,p'-DDD from faeces was about five times higher after ingestion of tablets than after administration in oil emulsion and milk. As far as the rapid increase in plasma levels and patient compliance are concerned, the best results were obtained with the milk powder mixture.
The distribution of o,p'-DDD in various body compartments of patients being treated for metastatic adrenocortical carcinoma was studied. A highly significant semilogarithmic relationship was found between plasma and adipose tissue concentrations during therapy and between plasma and brain at autopsy. A linear relationship was found at autopsy between concentrations in adipose tissue and those in various other tissues, such as tumour and brain. The semilogarithmic relationship can be explained by the assumption of two plasma pools for o,p'-DDD, one with low affinity and high capacity and one with high affinity and low capacity. Plasma concentrations must be carefully monitored to obtain an impression of the tumour concentration and to detect impending central nervous system intoxication.
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