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.

Spinal cord compression from metastatic Leydig's cell tumor of the testis: case report.

A case of spinal cord compression from metastatic Leydig's cell tumor of the testis is presented. This 67-year-old man exhibited paraparesis and neurogenic bladder dysfunction secondary to a spinal epidural mass at the T5 level as the initial manifestation of his cancer. Surgical resection was undertaken for tissue diagnosis and spinal cord decompression. The histopathological features of the epidural mass and the excised left testicle were identical, indicative of Leydig's cell carcinoma. The literature is reviewed for previous experience with this exceedingly rare tumor. Unlike most metastatic spinal malignancies, radiation therapy is an ineffectual treatment modality for this tumor. Surgical resection is the only therapeutic option available for amelioration of spinal cord compression.

Perioperative management and surgical outcome of the acromegalic patient with sleep apnea.

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.

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.

PURPOSE: To 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). METHODS: 311 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. RESULTS: The 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 < or = 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. CONCLUSION: The trial showed a survival advantage to the group randomized to PCNU, although the difference was modest. Coupled with previous BTCG results, these trails suggest that PCNU is an active drug for brain tumors.

Familial occurrence of subependymoma. Report of two cases.

Subependymomas are unusual tumors believed to arise from the bipotential subependymal cell. Previous reports of familial occurrence of subependymoma have involved monozygous twins and siblings. The authors describe the first reported occurrence of fourth ventricular subependymoma in a father and son, suggesting the possibility of direct inheritance.

Interstitial brachytherapy versus cytoreductive surgery in recurrent malignant glioma.

In selected patients with recurrent malignant glioma, interstitial brachytherapy has been advocated as an effective method for tumor control and prolonged survival. We are presenting our results with brachytherapy in patients with recurrent glioma, and comparing this technique with cytoreductive surgery. Twenty patients (9 male, 11 female) underwent stereotactic 125I implantation for recurrent malignant glioma (9 grade III, 11 grade IV). The average age was 43 years and the average Karnofsky score was 76. All patients had received radiation therapy following their initial surgical procedure and 17 received chemotherapy. The median interval from initial procedure to implantation was 70.5 weeks. The median survival following implantation was 24 weeks and total median survival for the group was 94.5 weeks. This group was compared to a contemporary series of 22 patients (16 male, 6 female) who underwent cytoreductive surgery for malignant glioma (10 grade III, 12 grade IV). The average age was 44 years and the average Karnofsky score was 76. All patients received radiation therapy following their initial procedure and 20 patients also received chemotherapy. The median interval from initial procedure to second procedure was 35.5 weeks, and from the second procedure to death was 28 weeks. The median survival for the group was 63.5 weeks. The interval from the first procedure to the second procedure was statistically significant comparing the implant group (median 70.5 weeks) versus the cytoreductive surgery group (median 35.5 weeks; p = 0.04). No significant difference could be demonstrated between the interval from second procedure to death in the implant group (median 24 weeks) versus cytoreductive surgery group (median 28 weeks; p = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Ganglioglioma: 13 years of experience.

A 13-year retrospective review of 17 patients with gangliogliomas treated at the University of Iowa was conducted to investigate the association between tumor location, extent of resection, pathological findings, and patient prognosis. Thirteen were in the cerebral hemispheres and 4 in the midline. The mean ages at diagnosis and symptom onset were 16 and 8.8 years, respectively. The most common presenting symptom was seizures (11 patients); focal neurological deficit was seen in 5 patients and headache in 1. Patients with hemispheric tumors had an older age at time of diagnosis and a longer duration of symptoms. Pathologically, they had more microcalcifications, lymphocytic infiltration, microcystic degeneration, and eosinophilic bodies. Cerebral hemispheric tumors were more amenable to total resection than midline neoplasms, 77% versus 25%, respectively. In the patients with hemispheric tumors, 10 patients were tumor-free after total resection. Two of the 3 patients with partial resection had stable residual tumors. The third died of tumor progression. In the 4 patients with midline neoplasms, one was tumor-free after total resection. The other 3 had subtotal resection and radiation therapy. Two died within 2 years; the third is still alive with progressive tumor. Five of 9 patients who had seizure disorders and who underwent total tumor removal were seizure-free postoperatively. The other 4 patients and the 2 with partial surgical resection continued to have seizures.

A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma.

This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.

Brachytherapy for malignant recurrent and untreated gliomas.

Twelve consecutive patients with recurrent malignant glioma were treated with brachytherapy. Thereafter, a prospective randomized study involving 35 patients was undertaken. Although additional study is necessary, preliminary recommendation calls for treatment at diagnosis rather than at recurrence.

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.

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 Cushing's 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.

Symptomatic Chiari malformations. An analysis of presentation, management, and long-term outcome.

The Chiari malformation is a condition characterized by herniation of the posterior fossa contents below the level of the foramen magnum, and is categorized into three types based on the degree of herniation. The authors review their surgical experience between 1975 and 1985 with 50 patients afflicted with symptomatic Chiari malformations. Any patient with associated myelomeningocele, tethered spinal cord, lipoma, or diastematomyelia was excluded from this series. Forty-one patients had Chiari I malformations, seven were classified as having Chiari II, and two as having Chiari III. The presentation of pediatric and adult patients was identical. Treatment was directed at the posterior fossa pathology. Seven patients with accompanying ventral bone compression underwent transoral decompression of the cervicomedullary junction, 42 had posterior decompressive procedures, and six received ventriculoperitoneal shunts. The posterior decompression included opening the outlet foramina of the fourth ventricle, occluding any communication between the spinal cord central canal and the obex, shunting the fourth ventricle, and placing a dural graft. Postoperatively, 20% of the patients are asymptomatic, 66% improved, and 8% stabilized; in 6% the disease has progressed in spite of multiple procedures. Preoperative signs that are predictive of a less favorable outcome include muscle atrophy, symptoms lasting longer than 24 months, ataxia, nystagmus, trigeminal hypesthesia, and dorsal column dysfunction (p less than 0.05, chi-square test). A model based on the presence or absence of atrophy, ataxia, and scoliosis at the time of the preoperative examination has been generated that allows prediction of long-term outcome at the 95% confidence level.

Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001.

Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.

Transoral-transpharyngeal approach to the anterior craniocervical junction. Ten-year experience with 72 patients.

The anterior transoral-transpharyngeal operation to correct ventral irreducible compression of the cervicomedullary junction was utilized in 72 individuals. The patients' ages ranged from 6 to 82 years, and 29 were children. The pathology encountered was primary basilar invagination, rheumatoid irreducible cranial settling, secondary basilar invagination due to migration of odontoid fracture fragments, dystopic os odontoideum, granulation masses, clivus chordoma, osteoblastoma, and chondroma of the atlas. Fifteen patients had associated Chiari malformation with basilar invagination. Fifty-two patients required subsequent atlantoaxial or occipitocervical fusion. Neurological improvement was the rule. There were two deaths within 30 days of surgery: one from myocardial infarction 4 weeks after surgery and one from Gram-negative septicemia of urinary tract origin. There was one pharyngeal wound infection. The ventral transoral approach provides a safe, rapid, and effective means for decompression of the abnormal craniovertebral junction.

The hypothalamic anterior pituitary relationships and their tumors. A review.

The hypothalamic pituitary axis is reviewed in relation to the regulation of the secretion of prolactin, growth, and adrenocorticotrophic hormones by the anterior pituitary lactotrophic, somatotrophic, and corticotrophic cells, respectively. The signs and symptoms, diagnosis, and treatment of tumors arising from these three separate anterior pituitary cells are discussed in the context of current literature.

Stereotaxic surgery in the treatment of multiple brain abscesses.

Controversy exists regarding the optimal treatment for patients with multiple brain abscesses. These lesions are often small and located deep in the brain and close to vital structures, making surgery difficult. With this in mind the authors review their experience in treating multiple abscesses using computerized tomography (CT)-guided stereotaxic aspiration. From 1983 to 1985, 15 patients were treated for multiple brain abscesses, of whom eight underwent stereotaxic aspiration. There were a total of 28 abscesses in these eight patients: 11 abscesses were aspirated and two excised using CT-guided techniques. Most were cortical in location, although there were 12 in the deep white matter, one in the thalamus, and two in the caudate nucleus. All patients received a total of 6 weeks of antibiotic therapy. Follow-up CT showed resolution of the abscesses in all patients. Currently, four are neurologically normal, one has a mild hemiparesis, one has a well-controlled seizure disorder, and one requires supportive care. A single death occurred 5 weeks postoperatively of unrelated causes. Location, size, and age of an abscess all have bearing upon the response to management and outcome of the patient. Stereotaxic surgery is a procedure with minimal morbidity and mortality. Stereotaxic aspiration should be considered in patients with small, multiple, or deep-seated abscesses, in those who are poor operative candidates, and in those who have failed prior therapy.

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.