John C. VanGilder

Pathogenesis of prolactin-secreting pituitary adenomas.

42 women with amenorrhoea and hyperprolactinaemia had trans-sphenoidal surgery and resection of histologically verified pituitary adenomas. 74% of these patients developed amenorrhoea and/or galactorrhoea in immediate association with the use or discontinuation of oral contraceptives or post partum. There was enough adenomatous tissue for immunocytochemical studies in 35 specimens and specific localisation of prolactin was possible in 31. There is evidence that about 10% of the population have small pituitary tumours, and the majority of these tumours, though asymptomatic, are potentially prolactin-secreting. It is suggested that oestrogens, which are known to modulate prolactin secretion in normal human beings and in animals, can induce the growth and expression of otherwise silent pituitary lesions and that this should be considered a risk of oral-contraceptive use.

Pediatric pituitary tumors

This retrospective review of pediatric patients with pituitary tumors causing onset of symptoms by 17 years of age was done to define their pathological distribution, clinical presentation, treatment, and prognosis. Eighteen patients were evaluated and treated from 1979 to 1989. Five had Cushings disease and 13 had prolactin-secreting tumors. The mean age at the onset of symptoms was 14.7 years, with a range of 7 to 17 years. The mean follow-up period was 4.6 years, and the series consisted of 15 girls and 3 boys. Four of the 5 patients with tumors secreting adrenocorticotropic hormone were girls. The five patients exhibited obesity, hypertension, and growth retardation. The mean age of this group of patients at diagnosis was 12.2 years, and all had intrasellar lesions removed by the transsphenoidal approach. Adenoma was documented in 4 cases by histopathology. There was complete resolution of the endocrinological and clinical abnormalities in each case. The group of patients with prolactinomas comprised 11 girls and 2 boys, and their mean age at diagnosis was 15.7 years. The girls exhibited either primary or secondary amenorrhea. Seven had macroadenomas and 4 had microadenomas. Nine of the 11 girls underwent transsphenoidal resection, and surgery failed in 6, based on hormonal or radiological data. The two boys had suprasellar tumor extension and required multiple surgical procedures plus radiation therapy for control of the tumor mass.

The role of radiation therapy in the management of ependymomas of the spinal cord

Twenty patients with biopsy-proven ependymomas of the spinal cord were treated between 1960 and 1984-7 with surgery only, 3 with radiation therapy only, and 10 with surgery and postoperative radiation therapy. Of these, 2 patients developed recurrent tumor at the primary site, 3 developed a recurrent tumor in the thecal sac, and 1 developed distant metastasis. The absolute 5- and 10-year survival rates were 95% (19/20) and 86% (12/14), respectively. None of 13 patients who were treated with radiation therapy only or combined surgery and postoperative radiation therapy developed recurrent tumor at the primary site, and none of 7 patients who received thecal sac irradiation developed thecal sac recurrences. In contrast, 2 of 7 patients (29%) treated with surgery alone developed recurrent tumor at the primary site, and 3 of 13 patients (23%) who received no thecal sac irradiation developed a recurrent tumor in the thecal sac. The failure rates following surgery were greatest in patients who had tumor removed in a piecemeal fashion (43%, 6/14). The results show that radiation therapy is probably not necessary if the tumor has been removed completely in an en bloc fashion. However, radiation therapy is needed if the tumor has been incompletely removed or removed in a piecemeal fashion. If the tumor has been removed in a piecemeal fashion, the radiation portals should be extended to include the thecal sac. Histologic subtypes influenced the pattern of recurrence. Myxopapillary ependymomas and high grade cellular ependymomas appear to be more likely to recur in the thecal sac. However, no big difference could be detected in local recurrence.

Postoperative prophylactic anticonvulsant therapy in cerebral gliomas

A retrospective study was performed to evaluate the efficacy of prophylactic anticonvulsants in preventing seizures in 68 patients with supratentorial astrocytomas who had been treated with operation and irradiation and who had no previous history of convulsions. Thirty-three patients received prophylactic anticonvulsants and 38 patients did not. The incidence of all types of seizures (generalized convulsions or partial) was lower in patients receiving anticonvulsants. No seizures with an impairment of consciousness occurred in the patients with documented therapeutic anticonvulsant blood levels. The overall incidence of seizures was 39% in untreated patients and 21% in treated patients. The incidence of major seizures including tonic/clonic or partial complex seizures with impairment of consciousness was zero in patients with therapeutic anticonvulsant levels and 18% in untreated patients. Regarding the overall incidence of seizures in both groups, there tend to be fewer seizures in older patients, females, patients with a higher grade of malignancy, and patients who had a more radical resection of the tumor. This study suggests that seizures are a frequent occurrence after operation and irradiation for supratentorial glioma and that anticonvulsants may be effective in reducing the incidence of those seizures.

Herniated thoracic disks: treatment and outcome.

The optimal surgical approach for thoracic disk herniation is controversial, and long-term follow-up is poorly documented. We retrospectively reviewed the records of 31 patients who underwent surgery for herniated thoracic disks at our institution during a 17-year period (1975-1992). Two patients had multiple disk herniations; 16 of 33 herniated disks occurred at or below the T10-11 level. There were three surgical approaches to diskectomy: laminectomy in four patients, transpedicular surgery in 12, and costotransversectomy in 15. Weakness resolved postsurgery in nine of 18 patients. One patient transiently deteriorated neurologically after a laminectomy, three had wound infections, and two required second operations for their herniated disks. Postsurgery half the patients with symptoms continued to have pain or weakness.

Perioperative Management and Surgical Outcome of the Acromegalic Patient with Sleep Apnea

ABSTRACT: SLEEP APNEA IS a rare complicating factor of acromegaly associated with a high risk of perioperative airway compromise and unclear response to transsphenoidal resection of the underlying pituitary tumor. We reviewed four acromegalic patients with sleep apnea and documented postoperative objective and subjective improvement of their sleep disorders. The pathogenesis of this disorder and safe perioperative airway management are discussed.

Cerebral aneurysms associated with neurofibromatosis

An uncommonly recognized complication of neurofibromatosis (NF) is an angiopathy of the intracranial and extracranial arteries. Most of the previously reported cases have presented as an occlusive process similar to Moyamoya disease. We present our experience over the past 3 years involving three patients with five cerebral aneurysms and associated NF. Four of the aneurysms were intracranial, two being fusiform in nature. Treatment was surgical occlusion and included Selverstone clamping, balloon occlusion, and direct clipping. There appears to be an association between the development of cerebral artery aneurysms and NF, but the pathophysiology of these vascular changes is not fully understood.

Results of a randomized trial comparing intra-arterial cisplatin and intravenous PCNU for the treatment of primary brain tumors in adults: Brain Tumor Cooperative Group trial 8420A

SummaryPurposeTo test the efficacy of intra-arterial (IA) cisplatin versus intravenous (IV) PCNU for treating primary brain tumors, in a randomized trial (Brain Tumor Cooperative Group [BTCG] Trial 8420A).Methods311 adult patients (ages 19–79 years; median 45) with supratentorial tumors (confirmed histologically) were randomized by nine participating institutions. Patients were required to have completed radiotherapy (4500–6020 cGy to the tumor bed) before randomization. Patients were stratified as either nonprogressive (clinically and radiologically stable) or progressive. Results were analyzed for the 311 patients in the randomized population (RP), and for the 281 patients in the Valid Study Group (VSG) meeting protocol eligibility requirements. 56% of patients in the VSG had glioblastoma multiforme, 33% had other malignant glioma, and 11% had low-grade glioma. 64% were stratified as progressive. 12% had received prior chemotherapy.ResultsThe group randomized to PCNU had the longer survival (p = 0.06 for the RP, p = 0.07 for the VSG). In the VSG, median survival was 10 months for the cisplatin group, 13 months for the PCNU group. The difference between treatment groups was significant (p ≤0.02) when adjusted for important prognostic factors. PCNU lead to greater hematotoxicity; cisplatin lead to greater renal toxicity and some ototoxicity. Some cisplatin patients experienced complications associated with IA administration, including six cases of encephalopathy.ConclusionThe trial showed a survival advantage to the group randomized to PCNU, although the difference was modest. Coupled with previous BTCG results, these trials suggest that PCNU is an active drug for brain tumors.

Influence of adhesion molecule expression by human brain microvessel endothelium on cancer cell adhesion.

Cultures of endothelial (En) cells derived from human brain microvessels were established in order to characterize adhesion molecule expression and to assay the adhesion properties of neoplastic cell lines to monolayers of En cells. Low constitutive expression of beta1 integrin (CD29), and ICAM-2 (CD102) was detected on human brain microvessel En cells. The beta1 chain of the VLA integrin family, ICAM-1, E-selectin (CD62E) and VCAM-1 (CD106) but not ICAM-2 and PECAM-1 (CD31) expression was upregulated by IL1-alpha, and TNF-alpha proinflammatory cytokines. High expression of PECAM-1 was found on non-activated human brain EN cells. In order to study the potential role of adhesion molecules in neoplastic cell adhesion two tumor cell lines were chosen. Adhesion of a cell line (DU145) derived from a cerebral metastasis of prostate carcinoma to human brain microvessel En cell monolayers was less pronounced compared to adhesion of a primary prostate carcinoma cell line (ND1). Adhesion of cerebral metastatic neoplastic cell line (DU145) was not significantly influenced by incubation of endothelial cells with different proinflammatory cytokines. The adhesion capability of primary prostate carcinoma line (NDI) was significantly upregulated by TNF-alpha proinflammatory cytokine. Furthermore, the adhesion of ND1 was partly inhibited using anti-E-selectin and VCAM-1 monoclonal antibodies. There was no significant effect of anti-adhesion antibodies on the adhesion characteristics of the cerebral metastatic (DU145) cell line. Our data demonstrate that different mechanisms are involved in the adhesion of neoplastic cells to cerebral En cells and turn our attention to the importance of adhesion molecule expression in the formation of metastases.

A Combined Surgical Approach to Non-Oat-Cell Pulmonary Carcinoma with Single Cerebral Metastasis

Eighty consecutive patients with pulmonary non-oat-cell carcinoma and a single cerebral metastasis were followed for at least 5 years after therapy. Forty were treated by surgical excision at both sites of disease plus whole-brain irradiation in most cases (group 1). The remaining 40 patients, an observational cohort, were treated either by surgery at only one site of disease (usually craniotomy), whole-brain irradiation, chemotherapy, or some combination of these modalities (group 2). The 1-year survival in group 2 was 15%, and all were dead at 2 years. In group 1, hospital mortality was 1.5%, the 1-year survival rate 35%, the 2-year survival rate 25%, and the 5-year survival rate 12.5%. All the five year survivors were patients with N0 disease. In this subgroup of group 1, the five year survival was 20%. All patients surviving for more than 2 years were in group 1 and had a Karnofsky rating greater than 50 and N0 disease after staging. These data indicate that a combined surgical approach can be accomplished with low morbidity, low mortality, and increased survival rates, especially for patients with N0 disease who are vigorous enough to undergo the combined treatment.