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James N. Domingue, S. Douglas Wing and Charles B. Wilson

✓ Seventeen cases of coexisting secreting pituitary adenomas and partially empty sellas are presented. The location of the cisternal invagination into the sella was not helpful in predicting the location of the tumor. In patients with endocrine indication of a secreting pituitary neoplasm, the finding of a partially empty sella should not contradict the diagnosis.

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Charles B. Wilson and Lawrence C. Dempsey

✓ In a series of 250 pituitary adenomas, 72 (28.8%) were nonsecreting and 178 (71.2%) produced a hypersecretion syndrome: human growth hormone (83), prolactin (59), and adrenocorticotropic hormone (ACTH) (36). One-fifth had received prior treatment and one-fourth had visual impairment. The technical aspects of the trans-sphenoidal procedure are given with separate consideration of microadenomas and larger tumors. The results are provided in summary form with emphasis on the favorable outcome following removal of microadenomas. There was one postoperative death, and the complications observed after operation are presented.

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Sang U Hoi, Charles B. Wilson and J. Blake Tyrrell

✓ From July, 1970, to March, 1975, 62 transsphenoidal operations were performed on 61 acromegalic patients (39 males, 22 females). Of these patients, 58 presented with symptoms of hypersecretion of human growth hormone (HGH), with relatively infrequent local effects. Each patient was evaluated neuroradiologically, and each tumor was classified as an enclosed or an invasive adenoma, with or without suprasellar extension. Anterior pituitary function was also evaluated for each patient, pre- and postoperatively. During the transsphenoidal procedure, selective gross total removal of the adenomatous tissue was attempted, and was successful in 53 patients; selective subtotal tumor removal was performed in eight patients.

In 38 patients who had not undergone prior therapy, a selective total excision was achieved in 36; of these, 30 patients were considered cured, on the basis of relief of clinical symptoms and reduction of the serum HGH level to below 10 mg/ml. There was no significant difference in cure rates between the enclosed and the invasive adenomas, and no cures were achieved by any procedure short of selective total tumor removal. In these latter cases, postoperative irradiation was employed. Eighteen patients had received prior therapy in the forms of cryohypophysectomy (eight cases), cryohypophysectomy and irradiation (two cases), craniotomy (two cases), craniotomy and irradiation (two cases), and irradiation alone (four cases). The treatment results in this group were less favorable. In the entire series of 62 operations, complications occurred in eight patients in the form of cerebrospinal fluid leak, meningitis, sinusitis, nasal-oral fistula, transient diabetes insipidus (six cases), and carotid and cavernous injuries. In the group of 43 previously untreated patients, endocrine complications occurred in five, of which only three have permanent deficits. In the previously treated 18 patients, one developed compromised pituitary function from the transsphenoidal procedure. In the entire series, there was no surgical mortality, although two patients died of surgically unrelated causes.

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Darell D. Bigner and Charles B. Wilson

✓ The authors provide a summary of a workshop on “Cancer of the Brain.” This conference reviewed the current knowledge about the etiology and pathogenesis of human brain tumors and the experimental induction of comparable animal brain tumors, and considered new lines of research.

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Constantine Mavroudis, Jeannette J. Townsend and Charles B. Wilson

✓ A case is described in which a metastatic ependymoma of the cauda equina recurred after prolonged remission. Similarities to five previously reported cases are discussed, with emphasis on the mode of metastasis. Factors most closely associated with distant metastases include early onset, numerous local operations, long survival, and massive local recurrence at the time of distant metastases.

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Victor A. Levin, David C. Crafts, David M. Norman, Paul B. Hoffer, Jean-Paul Spire and Charles B. Wilson

✓ The authors describe their criteria for evaluating brain-tumor patients, and present a numerical rating scale devised to designate response to testing. They discuss the reliability of test combinations that permit accurate prediction of response or deterioration during therapy in their experience with 100 patients treated on the Chemotherapy Service at the Brain Tumor Research Center, University of California, San Francisco School of Medicine. Specifically, the paper summarizes the predictive value of the neurological examination, radionuclide scintiscan, computerized tomographic brain scan (CT scan), and electroencephalogram (EEG), in the determination of response (tumor regression) or deterioration (tumor growth) during brain-tumor chemotherapy and chemotherapy-radiotherapy.

By retrospective analysis, the neurological examination, radionuclide scintiscan, and CT scan were of equal value individually as tests to predict response to therapy. However, the prognostic values of the neurological examination or the radionuclide scintiscan proved moderately superior to the CT scan in predicting deterioration during therapy. Under circumstances whereby a neurological examination, radionuclide scintiscan, and CT scan were all performed during the same testing session, and steroid dosage was carefully monitored, two of the three tests accurately predicted deterioration in 65% of patients, and response to therapy in 82% of patients. Two of the three tests correctly established deterioration in the remaining 35% of patients, and response in the remaining 18% of patients, when the two positively correlated tests had occurred within a mean period of 7 weeks.

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Robert F. Spetzler, Philip R. Weinstein, Norman Chater and Charles B. Wilson

✓ The authors describe a shunt inserted by a percutaneous route to the cisterna magna for the treatment of various cerebrospinal fluid disorders.

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Pituitary abscesses

Report of seven cases and review of the literature

James N. Domingue and Charles B. Wilson

✓ Seven cases of pituitary abscess are presented and the relevant world literature is reviewed. An enlarged sella co-existing with bacterial meningitis, or bacterial meningitis coinciding with a known or suspected pituitary tumor should suggest the diagnosis of pituitary abscess. Visual field defects should evoke similar suspicion when present in a patient with meningitis. This reasoning enabled us to make the first reported preoperative diagnosis of pituitary abscess. Therefore, in the management of purulent meningitis, we recommend the following: first, skull films are mandatory; second, if the sella turcica is abnormal, the correct presumptive diagnosis is pituitary abscess; and third, if prompt improvement does not follow appropriate antibiotic therapy, the suspected abscess should be explored and drained via the transsphenoidal approach.

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Brain-tumor therapy

Quantitative analysis using a model system

Mark L. Rosenblum, Kathy D. Knebel, Dolores A. Vasquez and Charles B. Wilson

✓ A recently developed colony-formation assay has been used to evaluate in vivo 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) therapy of a transplantable rat brain-tumor model. A comparison of the in vitro colony-forming capacity of treated and untreated tumor cells permits calculation of the fraction of clonogenic tumor cells surviving in vivo therapy. The plateau that we previously observed on the BCNU dose-response curve is not the result of repair of potentially lethal damage, since no change in the 0.1% of surviving clonogenic tumor cells occurs during the first 2 to 4 days after treatment. Although reanalysis of the dose-response curve indicates that sublethal damage exists, its repair is probably minimal. The most likely explanation for the observed limitation of the BCNU effect is the drug's failure to reach all clonogenic cells. A dose of BCNU that kills more than 99.9% of clonogenic tumor cells within 30 minutes of treatment results in only a 60% decrease in tumor weight by Day 14. This disparity is explained by retarded removal of dead cells, and, along with a previously determined 90% cell-kill threshold necessary to appreciate increased animal survival, demonstrates the inherent limitations of measurements of tumor size (including brain scans and clinical patient evaluations) in evaluating the efficacy of brain-tumor therapy. Following an LD10 dose of BCNU the surviving clonogenic tumor cells increase in number after a latency period of 2 to 4 days; during regrowth the cell doubling time is 40 hours. Marked variability in tumor response and regrowth was noted. The determination of information regarding disturbed tumor cell kinetics and tumor heterogeneity is essential for the proper planning of combination chemotherapy and multimodality regimens.

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