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This report describes two cases of cardiotoxicity associated with the use of 5-fluorouracil (5-FU) in the treatment of neoplastic disease, and reviews the literature to date. The manifestations of cardiac toxicity were significant ventricular dysfunction during continuous infusion of 5-FU, accompanied by symptoms resembling cardiac ischemia in one case and irreversible cardiogenic shock in another. Detailed cardiac investigations and pathological findings provide convincing evidence that the development of acute myocarditis is the likely mechanism of 5-FU cardiotoxicity, rather than coronary insufficiency as has commonly been postulated. Although cardiotoxicity as a complication of 5-FU therapy remains rare, recognition of this entity is important as it may lead to serious hemodynamic compromise and may recur with drug rechallenge.

Unusually large, oval and pleomorphic secretory granules were noted by electron microscopy in an acidophilic adenoma of the pituitary. The tumor, which was removed by surgery from a 42-year-old woman with elevated blood growth hormone levels and the clinical features of acromegaly, was found to contain growth hormone by the immunoperoxidase technique. This ultrastructural abnormality of secretory granules was not reported so far and was not seen among the 58 cases of growth hormone-producing adenomas investigated in our laboratory. The present case clearly shows that the cytogenesis and cellular composition of pituitary adenomas cannot be determined by solely examining the size and shape of secretory granules.

A 45-year-old female with selective deficiency of C4 and systemic lupus erythematosus developed puzzling gastrointestinal and systemic symptoms in the last 6 months of her life. Extensive investigation of the gastrointestinal tract did not yield any diagnosis, and the patient died shortly afterwards. Autopsy revealed evidence of a typical Whipple's disease of the jejunum and lymph nodes. This association has not been previously described. The disease is reviewed with emphasis on its being an opportunistic infection in an immunosuppressed host with a complement deficiency and SLE.

A prospective randomized trial of 157 patients with malignant astrocytoma (Grade III or IV) was carried out at a single institution. The minimization technique ensured balanced distribution of prognostic factors between the treatment groups. All received oral lomustine (CCNU, 80 mg/m2) six weekly and hydroxyurea (HU, 3.5 gm/m2 over 5 days) three weekly, for one year or until recurrence, with doses adjusted for myelosuppression. Patients were randomized to daily (5000 rad in 25 fractions (fr) in 5 weeks) or Q3h (every 3 hours) Cobalt 60 irradiation (3600-4000 rad in 36-40 fr of 100 rad each, given 4 fr per day at 3-hour intervals over two weeks) Steroid therapy (up to 16 mg day dexamethasone) was permitted. Complications were moderate and equivalent in the two groups. No significant survival or toxicity differences were seen between the two groups. Age, initial performance status, and extent of surgical resection were found to be significant (P less than 0.01) prognostic factors for survival. Median survival of the whole group was 48 weeks with a minimum follow-up of one year. There was no advantage to large radiation fields. The hyperfractionation and daily regimens had similar efficacy and toxicity. Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease.

In the morphologic study of surgically-removed pituitary adenomas, histology, electron microscopy as well as immunocytochemistry at the light microscopic and ultrastructural level were used. In material of 370 adenomas, 226 tumors (61.7%) were found to derive from the “acidophil” cell line. Thirty-one of these were densely granulated growth hormone cell adenomas; 38 were sparsely granulated growth hormone cell adenomas; 1 was composed of densely granulated prolactin cells and 114 of sparsely granulated prolactin cells. The latter represent the most common tumor type in the human pituitary. Twentyone adenomas were mixed, consisting of growth hormone cells and prolactin cells; 17 tumors were classified as acidophil stem cell adenomas. The latter are immature, aggressive neoplasms assumed to originate in the common precursor of growth hormone cells and prolactin cells.