Tamoxifen modulation of carboplatin cytotoxicity in a human U-138 glioma cell line.

Glioma cells express high protein kinase C (PKC) activity, which may represent an important therapeutic target. Tamoxifen (TAM) has moderate PKC-inhibiting activity, blocking DNA synthesis and cellular proliferation in human glioma cells at concentrations that can be achieved therapeutically. Carboplatin (CBDCA), a second-generation platinum derivative, induces intra- and interstrand DNA-protein crosslinks producing inhibition of tumor-cell growth. In the present study, the effect of TAM, CBDCA, and the combination of both was evaluated against the human established U-138 glioma cell line during the exponential growth phase (48-72 h) by means of both the Biorad protein assay (BPA) method and Trypan blue exclusion study (TBES). Both TAM and CBDCA reduced the cellular growth rate, with a median 50%-inhibiting concentration (IC50) of 12.5 microM for TAM and 350 microM for CBDCA. The U-138 glioma cell line showed a moderate response to 100 microM of CBDCA, with < or = 10% reduction of the growth rate. The association of both chemotherapeutic agents induced a 98% reduction of the IC50 dose of TAM (0.1 microM), and a 71% reduction of the IC50 dose of CBDCA (100 microM). During the combinational TAM CBDCA exposure we observed a cytotoxic effect of TAM at concentrations lower than 0.1 microM, not recognized using it as a single drug. The differences observed among the IC50 doses (TAM, CBDCA, TAM-CBDCA) and among treated and untreated matched control cells were statistically significant (P < 0.01). Our results confirm previous observations about the efficacy in vitro of TAM against human glioma cell lines and show a marked enhancement of this activity by CBDCA.

Clinical and radiographic stabilization of intracranial glioblastoma. Report of a case treated after surgery with tamoxifen.

We report the case of a patient with a left temporal-parietal glioblastoma treated with subtotal surgical excision, radiotherapy and chemotherapy, with a single intravenous administration of carboplatin and continuous oral administration of tamoxifen (40 mg/daily). Two years after the patient presents a stabilization of clinical and CT picture. We discute the possible role of tamoxifen in prolonging the survival of selected patients with intracranial high-grade glioma.

Solitary eosinophilic granuloma of the calvaria.

AIMS AND BACKGROUND: Histiocytosis X is a condition characterized by an abnormal proliferation of histiocytes with a variable granulomatous and inflammatory component; bone involvement is almost always present. The aim of this study was to define the management of solitary eosinophilic granuloma (EG) of the calvaria in adult patients, in relation to the size and site of the lesion. METHODS: Fourteen patients, ranging in age from 7 to 45 years, with solitary eosinophilic granuloma of the calvaria were surgically treated by craniectomy or curettage and cranioplasty. We subgrouped the lesions into two types: A) lesions localized inside the diploë and/or compressing the cerebral parenchyma below but without dural infiltration; B) lesions with mainly intracranial growth, compressing the cerebral parenchyma and infiltrating the dura. The infiltrated dura mater in type B lesions was replaced with a dural patch. Cranioplasty was performed in lesions with a diameter of 4 cm or more and/or located in aesthetically exposed areas of the skull. RESULTS: None of the patients died during the study and no local or systemic recurrences were observed during follow-up (min. 3 yrs, max. 8 yrs). CONCLUSIONS: Surgical treatment of patients with isolated EG of the calvaria not only is simple and quick but also allows histological diagnosis of the osteolytic lesion. These patients do not require further adjuvant treatment. Cranioplasty should be performed when the lesion has a diameter of 4 cm or more, when it is located in aesthetically exposed areas of the skull such as the frontal or temporal bones, or when it produces alterations of the normal skull morphology.

Primary eosinophilic granuloma invading the skull base: case report and critical review of the literature.

A case of eosinophilic granuloma of the lesser wing of the sphenoid bone is reported. The patient was a 5-year-old white male, with left temporal-frontal headache, left III cranial nerve palsy, left exophthalmos and ptosis caused by an osteolytic lesion of the anterior clinoid process extending to the left optic canal and cavernous sinus. The patient underwent surgical resection of pathologic tissue. Pathologic diagnosis was eosinophilic granuloma of the sphenoid bone. Surgical management, postoperative prognosis and differential diagnosis of eosinophilic granuloma of the skull base are discussed along with a review of the literature.

Surgically verified case of optic sheath nerve meningocele: case report with review of the literature.

Optic sheath meningocele is rare; only approximately 31 cases have been reported. The term optic sheath meningocele has recently been proposed by Garrity and Forbes to describe primary CSF cysts of the optic nerve sheath, without apical mass or malformation of the cranio-orbital junction. Presenting symptoms are often related to involvement of the optic nerve, with a slow or rapid decrease of visual acuity. CT and MRI studies reveal a tubular-cystic enlargement of the optic nerve/optic sheath complex (on/onsc), with thickening of the optic nerve. Radiological differential diagnosis should include optic nerve tumors such as gliomas, meningiomas, and arachnoid cysts involving the optic nerve sheath. Up to now, it seems that early surgical management by means of optic nerve/optic nerve sheath decompression affords an improvement of visual function with minimal morbidity in patients who present a rapid decrease of visual acuity within 3-6 months. We present an additional case and discuss the clinical, radiological, and operative features of this pathological condition of the optic nerve sheath.

Cytochemical and microbiological testing of CSF and catheter in patients with closed continuous drainage via a lumbar subarachnoid catheter for treatment or prevention of CSF fistula.

A study was performed to evaluate the efficacy of closed continuous drainage (CCD) via a lumbar subarachnoid catheter for prevention or treatment of CSF fistulas. In addition to the analysis of the physical, chemical and biological properties of the CSF obtained, the catheters themselves were tested on removal to identify any microorganisms contaminating them. Other factors taken into consideration were the symptoms reported by the patients during positioning of the catheter and while it was in place, any variations in body temperature and local inflammatory effects on the nerve roots of the cauda equine and surrounding tissues. The low percentage of systemic and local infections observed testifies to the safety of this method, regardless of the duration of treatment.

Tamoxifen and carboplatin combinational treatment of high-grade gliomas. Results of a clinical trial on newly diagnosed patients.

Between April, 1992 and December, 1995, forty consecutive patients with a cerebral malignant glioma (WHO Grade III and IV) were enrolled in a trial consisting in surgery and post-operative administration of radiotherapy (4500-6000 cGy), carboplatin (CBDCA; dose of 450-600 mg/m2), and oral tamoxifen (TAM; at doses of 40, 80 or 120 mg/day). Two patients of the TAM group died in the postoperative period from a pulmonary embolism and myocardial infarction, respectively. The patients (all dosages combined) had a median survival time of 13 months from the time of diagnosis. The 12-month and 24-month survival rates were 52% and 32%, respectively. The median relapse-free survival time was 7 months. Patients treated with higher doses of TAM (80-120 mg/day) demonstrated a longer median survival rate (13 months both) and a longer 12-month survival result (58% and 76%, respectively). Patients who assumed TAM for a period longer than 3 months (group +3) have a higher median survival rate (16 months) and better 12-month and 24-month results (62% and 40%, respectively). Moreover, the median relapse-free survival time was 10 months (versus 6 months in group -3; p = 0.0038). However, it is not possible to exclude that patients of group +3 had a slower growing or a stable tumor and were well enough to assume TAM for a longer period. The results observed in the TAM-group have been compared with those of 40 matched controls treated with surgery, radiotherapy and CBDCA. These patients had a median survival time of 9 months (p = 0.04) and the 12-month and 24-month survival rates were 30% and 0%, respectively. The median relapse-free survival time was 4 months (p = 0.0014). These data suggest a potential role for combinational TAM-CBDCA therapy in the post-operative treatment of cerebral malignant gliomas; further clinical phase III trials, especially those with higher dosages of TAM are warranted.

Neurohypophyseal pilocytic astrocytoma invading the skull base.

We describe the clinical presentation, neuroradiological and histological findings of an unusual case of pilocytic astrocytoma of the neurohypophysis, and discuss the related surgical and prognostic issues of this neoplasm which invaded the skull base and the sphenoid sinus. Only four histologically proven cases of such a tumour have been reported in the English literature, and the pathological features and behaviour of this neoplasm still await definition.

Cystic lymphocytic hypophysitis, visual field defects and hypopituitarism.

A 45-year-old man presented with anterior pituitary failure, requiring thyroxine, hydrocortisone and androgen replacement. An MRI scan revealed a large cystic pituitary mass and thickening of the pituitary stalk. Over three years, diabetes insipidus and bitemporal hemianopia developed and the cystic mass had enlarged on MR scanning. Transphenoidal resection was performed with normalisation of the visual fields. Histology revealed lymphocytic hypophysitis, which is rare in men. The presentation with cystic enlargement is unique.

Spinal accessory nerve palsy due to neurovascular compression. Report of a case diagnosed by magnetic resonance imaging and magnetic resonance angiography.

The case of a young patient with left accessory nerve paralysis is reported. He had slight tilting of the head to the right side, developed over a period of about 6 months. On neurological examination hypotrophy of the left sternocleidomastoid and trapezius muscles was observed. MRI and MR-angiography imaged the presence of a neurovascular compression between the medulla oblungata, at the level of the nerve entry zone, and a vessel loop of an elongated left vertebral artery. In spite of the absence of a surgical demonstration it is our opinion that the neurovascular conflict is the cause of the accessory nerve palsy.

Utility of early postoperative MRI in hindbrain-related syringomyelia. A preliminary prospective study on five patients.

We report a series of five patients operated on for hindbrain-related syringomyelia with posterior fossa decompression and duraplasty. In all cases an early postoperative MRI was performed (24-36 h after surgery). These images have been compared with the preoperative ones and with those obtained, 1, 3 and 6 months after operation. Both before and after surgery there was not always a tight correlation between clinical and MRI pictures. In all but one patient the early postoperative MR images showed a reduction of syrinx size and were as to those obtained later. We discuss the results observed in our small series and analyze the role of early postoperative MRI studies in patients with hindbrain-related syringomyelia.