In 50 consecutive patients with cancer-associated hypercalcemia, we measured nephrogenous cyclic AMP, tubular phosphorus threshold, fasting calcium excretion, plasma 1,25-dihydroxyvitamin D, and immunoreactive parathyroid hormone as determined by four region-specific antiserums. Nephrogenous cyclic AMP excretion was elevated in 41 patients and suppressed in nine (means, 5.85 vs. 0.51 nmol per 100 ml of glomerular filtrate). There was no overlap between these groups. When compared with 15 patients with primary hyperparathyroidism, the group with increased cyclic AMP excretion had similar reductions in tubular phosphorus threshold; higher fasting calcium excretion (means, 0.66 vs. 0.25 mg per 100 ml of glomerular filtrate, P < 0.01); marked reductions in 1,25-dihydroxyvitamin D (means, 20 vs. 83 pg per milliliter, P < 0.001); and lower levels of immunoreactive parathyroid hormone in all four assays. The data suggest that elevated excretion of nephrogenous cyclic AMP may be a useful marker of humorally mediated cancer-associated hypercalcemia, that this type of hypercalcemia is common, that the humoral factor responsible for this syndrome is not native 1-84 parathyroid hormone, and that the various subtypes of cancer-associated hypercalcemia are biochemically distinguishable from primary hyperparathyroidism.
A retrospective review of 1539 patients with cancer of unknown primary site seen at Yale-New Haven Hospital from 1922 to 1981 was performed. Information was obtained from the Tumor Registry. The method of diagnosis, patient characteristics, year of diagnosis, histologic features, treatment received, and survival were analyzed. The most common cell type was adenocarcinoma. Survival overall was poor, with a median survival of 5 months for the entire group. Age and year of diagnosis did not appear to significantly influence survival. Closer examination of a small subset of those patients with squamous cell carcinoma revealed a very high ma1e:female ratio, possibly related to tobacco and alcohol abuse. Nearly 9% of these patients were found to have a history of one or more unrelated malignancies.Cancer 57:120-124, 1986.E.rAsTA-ric CANCER of unknown primary site is a M persistent and perplexing problem. The incidence of metastatic malignant disease of undetermined origin generally ranges between 0.5% and 7.0%, depending in part upon the scope and duration of the diagnostic investigation.' The diagnosis was ranked as the eighth most common site of cancer in one large series,2 and may constitute 10% to 1590 of referred patients with solid tumors.',4The median survival from the time of diagnosis has ranged from 2 to 6 months, with less than 25% of patients surviving beyond 1 How exhaustive the search for the primary tumor should be is difficult to define." The major purpose ofan extensive examination of the patient with occult primary cancer is to identify a neoplastic process for which extended survival or cure is possible with an accepted treatment." Generally, only 10% to 15% of patients will have tumors for which effective systemic therapy is available.' A second popular reason to continue the search is to identify a cancer for which there is no known effective therapy, in which case no treatment need be given, thus preventing the toxic side effects of useless treatment. Because of the improved diagnostic methods and the use of more aggressive systemic chemotherapy for cancer patients available during the last decade. we believed that
Thirteen leukemic patients with disease refractory to conventional chemotherapy were treated with 1.0 to 7.5 g/m2 of Cytosine Arabinoside (Ara-C) over 29 drug cycles. Drug infusions were spaced at 12-hour intervals; a maximum of four doses was administered over 36 hours. After single dose tolerance had been established, three or four dose cycles were given at 2- to 30-day intervals. There were three partial remissions (PR) and one complete remission (CR) in a treatment group of four patients with AML, five with ALL, two with lymphoma converted to leukemic phase, one CML in blast crisis, and one promyelocytic leukemia. Five of the patients were septic and considered terminally ill at the time of treatment. All other patients had evidence of drug responsiveness. The nadir of the white count occurred from 3 to 12 days after treatment, with subsequent recovery of the peripheral granulocyte count between days 12 and 28. Toxicity included nausea and vomiting (GI symptoms) in twelve patients, central nervous system (CNS) disturbances in eight patients, one episode of inappropriate antidiuretic hormone syndromes (SIADH), one of hyperuricemia, and fever in eleven patients. There was no evidence of hepatic or renal dysfunction. These high doses of Ara-C appear useful for treatment of patients with refractory leukemia. Hospitalization is brief and toxicity acceptable.
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