Expression of vascular endothelial growth factor receptor-1/-2 and nitric oxide in unruptured intracranial aneurysms.

The biological mechanisms associated with the development and rupture of intracranial aneurysms are not fully understood. To clarify the role of VEGF and the related receptors in the pathophysiology of aneurysm, immunostaining for VEGF, VEGFR1 and VEGFR2 was performed on specimens from six unruptured aneurysms and on two specimens of normal arteries wall as a control. The results were correlated with NO concentration of CSF collected during surgery from 8 patients affected by unruptured aneurysms and in 11 control patients. The immunohistochemical data showed a different pattern of VEGF/VEGFR1/VEGFR2 in aneurysms when compared with control. The results of this preliminary study suggest an imbalance of VEGF, VEGFR1 and VEGFR2, and the interaction of VEGF and NO in the pathophysiology of unruptured aneurysms. Our data support the hypothesis of aneurysm formation associated with a loss of expression of VEGFR1, moderate expression of VEGFR2 and high concentration of nitrate.

Cerebral germ cell tumor and XXY karyotype.

Metaphases from a cultured cerebral germ cell tumor (CGCT) in a boy with a 46,XY constitutional karyotype had 47 chromosomes with an additional X chromosome and a translocation (1;21)(q11;p11). CGCT appear to be nonrandomly associated with Klinefelter syndrome, and a supernumerary X chromosome and trisomy of the 1q21-->1qter region may be clonal abnormalities in these tumors. The predisposition of Klinefelter patients to develop CGCT may be due to the pathogenetic relevance of the extra X chromosome both as an acquired and a constitutional abnormality.

Correlation between cytogenetic and histopathological findings in 65 human meningiomas.

The correlations between cytogenetic and histopathological findings were analyzed in 65 cases of human meningiomas. Clonal chromosome abnormalities were present in 28 cases (43%). The overall female/male ratio was 1.7, but it was 1.1 in the group of 28 cases with chromosomal abnormalities. Abnormalities of chromosome 22 as sole abnormality predominate in the female patients. The mean age of patients with normal karyotype was significantly lower (50.7 years) than that of patients with chromosome changes (57.3 years). The tumor origin was predominantly at the base in the patients with normal karyotype but different at the convexity, falx cerebri, and spinal cord. The five abnormal cases from the spinal cord all showed involvement of chromosome 22. The proportion of chromosome anomalies was different in the various histological types, and a significant difference was found between the meningotheliomatous (23%) and psammomatous (58%) types. The cytogenetically abnormal cases of the psammomatous type all showed involvement of chromosome 22. In three patients with multiple meningiomas, we found different karyotypes in the different tumors of the same patient, which may indicate a multifocal origin of the tumors.

Combined anterior craniofacial resection for tumors involving the cribriform plate: early postoperative complications and technical considerations.

OBJECTIVE: Combined craniofacial resection has become the standard approach for malignant tumors involving the cribriform plate and anterior cranial fossa. Despite its widespread application, however, many surgeons agree that the procedure carries a risk of significant morbidity and even mortality. The purpose of this study was to analyze the experience at a single institution to determine the incidence of early postoperative complications encountered after combined craniofacial resection of tumors involving the cribriform plate and to provide information to improve management. METHODS: Between 1987 and 1997, 168 patients underwent combined craniofacial resection at the National Cancer Institute of Milan for tumors involving the cribriform plate. Patient charts, operative notes, follow-up clinic notes, radiographic studies, and pathology reports were analyzed. Morbidity encountered in the first 30 cases was compared with that encountered in the subsequent 138 cases. RESULTS: The most frequently encountered pathological findings were adenocarcinoma (53.6%), squamous cell carcinoma (17%), and esthesioneuroblastoma (9.8%). Eight patients (4.7%) died, 6 of whom were among the first 30 patients to undergo resection. Among patients with fatal complications were three with meningoencephalitis, three with intracranial hemorrhage, and one with myocardial infarction. Fifty patients (29.7%) had nonfatal morbidity; 16 of these patients were among the first 30 patients operated. Transient cerebrospinal fluid leakage was the most frequent adverse effect (9.5%); 12 patients (7.1%) had pneumocephalus, 3 (1.8%) had meningitis, 4 (2.4%) had wound infections, 3 (1.8%) experienced transient impairment of mental status, 3 (1.8%) had transient diplopia, 2 (1.2%) had diabetes insipidus, and 1 (0.6%) had bone flap necrosis. CONCLUSION: We observed a dramatic decrease in mortality and morbidity in patients who underwent combined craniofacial resection after the first 30 cases in our series. Improvement of specific aspects of surgical technique, such as more refined reconstructive methods and improved prophylactic antibiotic therapy, is at least partly responsible for this favorable trend.

Spinal meningiomas: review of 174 operated cases.

The long-term results obtained in a series of 174 patients operated on for spinal meningiomas are critically analyzed. This series was similar to those of other authors with regard to age, sex, location of the tumors, and clinical presentation. Before surgery, about 70% of the patients were included in Groups I and II (mild neurological impairment), and about 30% of the patients were classified in Groups III and IV (significant to severe neurological impairment, up to paraplegia). Complete tumor removal was achieved in 96.5% of the patients, and surgical mortality was about 1%. Microsurgical technique, which was adopted in the last 29 cases, proved to be very effective in reducing undue damage to the spinal cord and in minimizing the postoperative neurological deficits. Of the 174 patients who underwent surgery, 156 underwent late follow-up study for an average of 15 years (2 patients died in the immediate postoperative period, and 16 patients were lost to follow-up). Twenty-nine patients died of causes unrelated to the spinal meningioma; of the remaining 126 patients, 92% were categorized in Groups I and II, and only 8% in Groups III and IV. The rate of recurrence was 6% (9 patients) among the 150 patients who had complete tumor removal, and the rate of regrowth was 17% (1 patient with anaplastic meningioma) among the 6 patients treated by subtotal removal. The early diagnosis of the disease and the use of microsurgical technique appeared as the most relevant factors for further improvement of the surgical results.

Meningiomas of the lateral ventricles. Neuroradiological and surgical considerations in 18 cases.

The clinical and neuroradiological findings and the surgical results in a series of 18 patients with meningiomas of the lateral ventricles, operated on over a 23-year period, are described. This experience is compared with previously reported series and the following conclusions are drawn: 1) these tumors have no characteristic symptomatology; 2) the preoperative diagnosis should be reached by means of both computerized tomography and carotid and vertebral angiography; 3) the safest surgical approach is through a sagittal paramedian parieto-occipital cortical incision; and 4) piecemeal removal is crucial for achieving total extirpation of the tumor with minimum damage of the surrounding brain tissue and for careful intraoperative hemostasis.

Determination of cerebrospinal fluid shunt function with water-soluble contrast medium.

Determination of cerebrospinal fluid shunt patency with water-soluble contrast medium is a simple, rapid, reliable, and safe technique. Since September, 1974, the authors performed 113 examinations. With the Spitz-Holter valve, only the atrial catheter can be studied, but, with the Pudenz valve and with the shunting devices that have a double-dome reservoir, both the proximal and the distal catheter can be visualized. Through the ventricular catheter a full ventriculographic study can be made, demonstrating ventricular size, malposition of the catheter, and the lesion that caused the hydrocephalus, or its evolution. The problem of collapsed ventricules, in which clinical and "manual" evaluation of the flushing device can give misleading findings, is emphasized. The injection of the atrial or peritoneal catheter in the pathological cases demonstrated its blockage, level of disconnection, malposition, sleeve, or cyst formation. Computerized tomography has only slightly decreased the number of these studies: when the ventricles are large, the examination with water-soluble contrast medium is still needed to demonstrate the exact level of malfunction. This demonstration has decreased the number of the total revisions complete changes of shunting systems, eliminating some unnecessary changes of normally functioning catheters.

A new classification for malignant tumors involving the anterior skull base.

OBJECTIVES: To propose our clinical classification of malignant ethmoid tumors and to compare it with the last American Joint Committee on Cancer (AJCC)-Union Internationale Contre le Cancer (UICC) classification, published in 1997. DESIGN: Retrospective review. SETTING: Tertiary cancer facility. PATIENTS: We evaluated 123 consecutive patients undergoing craniofacial resection for malignant ethmoid tumors involving the anterior skull base. The mean follow-up was 60 months. Fifty-nine patients (48%) presented with recurrent disease after prior therapy. We classified them with a new classification system (Istituto Nazionale per lo Studio e la Cura dei Tumori) based on the most commonly accepted unfavorable prognostic factors (involvement of dura mater; intradural extension; involvement of the orbit and, in particular, of its apex; invasion of maxillary, frontal, and/or sphenoid sinuses; and invasion of the infratemporal fossa and skin. We also classified patients with the AJCC classification published in 1997. MAIN OUTCOME MEASURES: Disease-free status and overall survival rate. To study a possible association with tumor stage, the Cox regression model was adopted. RESULTS: According to our classification, patient distribution by tumor type was T2, n = 46; T3, n = 29; and T4, n = 48 (no T1 tumors were present in the series). For previously untreated patients, 5-year disease-free survival estimates were T2, 57%; T3, 50%; and T4, 13%. For relapses, corresponding figures were T2, 31%; T3, 23%; and T4, 1%. The prognostic difference among stages was statistically significant (P<.001). Similar results were obtained for overall survival. In contrast, patient distribution among different AJCC stages was less balanced, and we failed to detect a significant association with the clinical outcome using this classification. CONCLUSION: We propose the use of our staging system by all those specialists in the field willing to validate the classification and possibly apply it for clinical and investigational purposes.

High-dose methylprednisolone reduces cytokine-induced adhesion molecules on human brain endothelium.

OBJECTIVE: We investigated the in vitro effects of low- and high-dose methylprednisolone (MP) on the cytokine-induced expression of HLA-DR, ICAM-1 and VCAM-1 on human brain microvessel endothelial cells (HBMECs). METHODS: Brain endothelium was obtained from microvessels included in the apparently normal white matter of surgical specimens of nine patients. Cells were stained with monoclonal antibodies anti-HLA-DR, anti-ICAM-1 and anti-VCAM-1 and analysed by flow cytometry as fluorescence histograms. The mean fluorescence intensity (MFI) of HBMECs treated with different stimuli was calculated. RESULTS: gamma-IFN-induced HLA-DR was down-regulated in a dose-dependent manner by MP. High-dose MP reduced the TNF-alpha-induced ICAM-1 and VCAM-1 expression. CONCLUSIONS: The down-regulation of adhesion molecules on cerebral endothelial cells could decrease mononuclear cell transmigration through the blood brain barrier and consequently the perivascular infiltrates. The results add support to the rationale for high-dose MP treatment in multiple sclerosis relapses.

Complete removal of a huge olfactory grooves meningioma in a child. Case report.

The clinical, radiological and histological findings of a huge olfactory grooves meningioma in a 14 years-old girl are described. Good result after complete removal is stressed and concerning literature is reviewed.

Preliminary data by cis-platin and etoposide using in primary glioblastoma.

In this preliminary study twenty-nine malignant glioma patients after surgery were treated using Cis-platin (CDDP) combined with etoposide (VP16). Superfractionated radiation therapy comes into chemotherapy. The time to tumor progression in GBM patients is encouraging result to continue in this treatment.

Late outcome of operations for supratentorial convexity meningiomas. Report on 207 cases.

Brief remarks on the immediate outcome of operations on 207 convexity meningiomas are followed by a fuller discussion of the late sequelae, the problem of recurrences and relevance of histology, and the persistence or de novo onset of epilepsy. While the immediate outcome is more than satisfactory, there is still room for improvement in the late outcome of surgical treatment for this category of intracranial tumor.

Immediate and late outcome of operations for Parasagittal and falx meningiomas. Report of 342 cases.

The immediate results of surgery--for the most part radical surgery--in 342 cases of parasagittal and falx meningiomas are presented. The late outcome in 317 survivors observed for at least five years and possible ways of avoiding them are discussed with special reference to recurrences and disabling sequels.

Skull base reconstruction after anterior craniofacial resection.

Anterior craniofacial resection has become a popular operation for nasoethmoid tumours involving the skull base. Many papers have been published since the first by Ketcham et al. in 1963. However, there is still controversy about the method for reconstruction of an anterior skull base defect after resection. The simple reconstruction of Ketcham has been followed by more sophisticated procedures using galeal-pericranial flaps, free flaps with microvascular anastomosis and bony or alloplastic augmentation. The main purposes of the reconstructions are to prevent brain herniation, to avoid intracranial infections, to diminish the risk of CSF leakage and to avoid pneumocephalus. From the relevant literature and our own experience of 168 anterior craniofacial resections, we conclude that a pedicled pericranial flap is the best choice for closing a cranial base defect.

Gene transfer of suicide genes for the treatment of malignant gliomas: efficacy, limitations, and perspectives for a combined immunotherapy.

The potential of gene therapy strategies for malignant gliomas that are based on retroviral-mediated transfer of a "suicide gene" such as Herpes Simplex Virus-thymidine kinase HSV-tk and subsequent treatment by a prodrug (ganciclovir, for example), has been emphasized by the promising results obtained by several groups. However, further experimental data as well as preliminary clinical results indicate that the low efficiency of retroviral-mediated gene transfer in vivo as well as difficulties for the diffusion of the prodrug inside the tumour mass can limit the efficacy of this form of gene therapy. To achieve a more effective limitation of tumour growth other approaches may be combined with the "suicide gene" strategy and the enhancement of the immunological response to the tumour by cytokine gene transfer is prominent among these approaches. The authors' experiments in nude mice confirm the antineoplastic role of IL-4 and encourage testing the effects of the simultaneous transfer of IL-4 and HSV-tk genes in immunocompetent animals.

[Anterior cranio-facial resection for malignant tumors: report of 91 cases]. / Resezione cranio-facciale anteriore per tumori maligni: esperienza di 91 casi.

Between 1987 and 1994 we performed 103 anterior cranio-facial resections in patients affected by tumors involving the ethmoid, the nasal cavities and, sometimes, the orbit, the maxillary and sphenoid sinuses. The cibriform plate was always involved. The tumor invaded the frontal dura in 20 patients without intradural neoplastic vegetations. These were present in 6 cases. Ninety-one of these patients had a malignant tumor; from the histologic point of view we had 50 adenocarcinomas, 16 epidermoid carcinomas, 8 estesioneuroblastomas, 6 adenoid cystic carcinomas, 5 melanomas and 6 infrequent types. The surgical technique became simplier in the second half of our patients. Now we perform a coronal skin incision and prepare a pericranial flap without the galea and use it to reconstruct the cranial base defect without bone or alloplastic material. The frontal craniotomy is rectangular, low and made by an oscillating saw without trephine holes. The posterior section of the skull base for a typical ethmoid tumor is always on the sphenoid roof and the lateral ones on the medial third of the orbital roof, al least in the more interested side. The anterior section is on the frontal sinus floor. The osteotomies may be enlarged according to tumor extension. Our facial incision is paranasal without splitting of the upper lip, but sometimes we used wider skin incisions and osteotomies for tumors involving the maxillary sinus and palate. We had many important complications in the first half of out patients with 7 postoperative deaths but none in the second half. Fifty-five percent of the adenocarcinomas, 7% of the epidermoid carcinomas, 75% of the estesioneuroblastomas, 100% of the adenoid cystic carcinomas and 0% of the melanomas are alive and well. Forty-six patients were previously treated elsewhere and 45 were untreated. The cure rate of these two groups of patients is very different: 38.1% of the first versus 61.9% of the second ones are alive and free of disease. Our experience proves that every transfacial or transnasal resection of an ethmoidal tumor involving the cribriform plate must be avoided.

[Classification of ethmoid malignancies]. / Classificazione dei tumori maligni dell'etmoide.

The UICC and AJCC never classified ethmoid malignancies prior to the latest edition (1997). Most classifications in the literature refer to a single histological type (estensioneuroblastoma or carcinoma) while others basically consider the intracranial extension, without distinguishing between intra or extradural. Still others consider invasion of the orbit. There is as yet no classification which considers all the prognostic factors associated with the extension of this neoplasm. The authors reviewed 84 patients with ethmoid malignancy who had undergone anterior cranio-facial resection between 1987 and 1994 and had been followed up for a minimum of 36 months. Of these patients, 43 were recurrences of previous treatment while 42 had not previously been treated. The breakdown was as follows: 45 adenocarcinoma, 14 squamous cell carcinoma (more or less differentiated), 8 etesioneuroblastoma, 6 adenoidocistic carcinoma, 5 melanoma and 6 rare forms. These cases were staged according to a new classification identifying the worst prognostic factors: invasion into the dura and, above all, intradural extension; invasion of the sphenoid sinus, orbit, and in particular the orbit apex, the frontal sinus, the maxillary sinus, the pterygoid, infratemporal fossa and the skin. Until 1994 we used this classification which is similar to the one proposed by the UICC in 1997. On the basis of this classification our case breakdown is as follows: T2 35, T3 24, T4 25 (there were no cases of T1). Since a patient can live as much as 4-5 years with a recurrence but the recurrences all appeared within 2 years after surgery, we used a NED survival at 36 months as index of healing. The NED survival at 36 months was: T2 54%, T3 41%, T4 8%. In patients which had not received prior treatment the NED survival was: T2 63%, T3 45%, T4 9%. The progressive worsening of prognosis from T2 to T4, particularly in patients which had not been pretreated, leads us to assume that the true prognostic factors for malignant ethmoid tumors have been identified.