Cranioplasty performed with a new osteoconductive osteoinducing hydroxyapatite-derived material.

OBJECT: Cranioplasty is required to protect underlying brain, correct major aesthetic deformities, or both. The ideal material for this purpose is autogenous bone. When this is not available, alloplastic or artificial materials may be used. These materials should be malleable, strong, lightweight, inert, noncarcinogenic, nonferromagnetic, and, if possible, inexpensive. The authors reviewed their surgical experience with a new bone substitute and discuss outcomes in patients in whom it was used. METHODS: The 11 patients presented in this series had bone defects resulting from bone-involving tumor (eight cases), trauma (two cases), or aesthetic deformity due to repeated craniotomies (one case). The defects were repaired using Osprogel, a bone substitute that consists of calcium hydroxyapatite combined with synthetic, human bone-derived gelatin, glycerol, and water. Osprogel is not only a bioinert material but also an osteoconductive and osteoinducing substrate; when it is placed in contact with healthy cancellous bone, it induces osteogenesis and angiogenesis, thus permitting the regrowth of nearly normal bone. The sheet of Osprogel was modeled onto the cranial defect intraoperatively and was kept in place either by using a titanium micronet secured to surrounding bone with microscrews (first two cases) or by using a single- or double-layer titanium mesh secured with stitches. No complications due to the procedure were observed. The results, evaluated at least 6 months after surgery by using three-dimensional (3-D) reconstructed computerized tomography scans, were excellent in seven patients, good in three, and fair in one. In the patient with a fair result, the repair was unsatisfactory because there was lack of experience in using the material. In part of the area to be repaired, the Osprogel was used as filler; here it was washed out and resorbed. The cases deemed as having a good result had good bone replacement; however, the curvature was faulty. CONCLUSIONS: In the near future, this technique may be refined to achieve good or excellent results either without the use of supporting material or with the use of individual, computer-designed 3-D prostheses.

Comparative analysis of proliferating cell nuclear antigen and epidermal growth factor receptor expression in glial tumours: correlation with histological grading.

The present study analyzed the combined immunostaining for proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGFR) with the aim of obtaining an objective method for the evaluation of the growth fraction in human glial tumors. A retrospective study was undertaken on 157 gliomas employing MoAb PC10 and MoAb 108, recognizing a 36 Kd nuclear protein associated with the cell cycle and the extracellular domain of the EGFR, respectively. The results of this immunohistochemical analysis showed that the rate of PCNA positive cell is directly associated to EGFR expression and significantly (P < 0.0001) correlates with tumor morphological grading, this was also the case in patients submitted to multiple surgical treatments for recurrent tumors. PCNA and/or EGFR are expressed by a minority of low grade astrocytoma, while anaplastic astrocytoma and glioblastoma displayed an intense immunoreactivity for the two antigens in more than 85% of tested cases. These findings indicate that the combined evaluation of PCNA and EGFR could allow a more definite biopathological grading of neuroepithelial brain tumours.

Epilepsy and gliomas: incidence and treatment in 119 patients.

One hundred and nineteen consecutive patients affected by supratentorial gliomas were studied in order to determine the incidence of seizure at diagnosis, the occurrence of subsequent seizures and the efficacy of anticonvulsant treatment. The overall incidence of seizures as presentation symptom was 52% (62 patients). Preoperative seizures were present in 83% of patients affected by low-grade astrocytoma, in 46% of patients affected by anaplastic astrocytoma and in 36% of patients affected by glioblastoma. Postoperative epilepsy refractory to anticonvulsant treatment significantly related to low-grade histology and presence of preoperative seizures occurred in 48% of patients. Adverse effects associated with anticonvulsants were observed in 33.8% of patients treated with phenobarbital, 14.3% in the group treated with carbamazepine and 12% of patients treated with vigabatrin. We conclude that anticonvulsant treatment in patients affected by gliomas is often ineffective and prophylactic treatment should be discontinued after 6 months in patients preoperative seizures free. In patients with high risk of seizures antiepileptic drugs with good efficacy and lower incidence of adverse effects than phenobarbital are indicated.

[Intracranial meningiomas in the elderly]. / Meningiomi endocranici dell'anziano.

BACKGROUND: Since the introduction of CT and then MRI in the clinical practice, the number of elderly patients with intracranial meningiomas observed in neurosurgical departments has increased to three/four times. Considering that some patients die because of their meningioma and others die with their meningioma, the neurosurgeon should not only be able to eradicate surgically the lesion, but also to decide if that benign tumor should be treated or not. MATERIALS AND METHODS: Forty-three patients with intracranial meningioma, aged over 65 were operated upon between 1989 and 1995. They constitute about one fourth of all the meningioma-patients operated upon in that period at our Department. Main symptoms were focal deficits, psychorganic syndrome, and seizures. Mean duration of symptoms was 15 months, with 30% of the histories lasting less than 3 months. Associate pathologies were those typical of the elderly population with hypertension and senile cardiopathy at the first places. Two patients had insulin-dependent diabetes, 2 prostatic carcinoma, and 8 were obese. MRI was useful either in depicting the location of the tumor or in helping the surgeon to give a correct operative indication and risk evaluation. MRI criteria for risk evaluation were severe edema and venous vascular infiltration. Forty-five operations were performed. Their duration was not a risk factor by itself, it only reflected the difficulty of the removal, due to the location of the tumor. Dissection of tumor remnants from main arteries or veins was never attempted in this group of patients; total removal was achieved in 75.5% of the cases. RESULTS: Immediate postoperative results were good in 71% of cases. Four patients died (9%). Long term results were evaluated in 29 patients (mean follow-up period: 35 months). Twenty-two patients (76%) had excellent or good results, 5 (17%) fair, and 2 (7%) had severe neurological dysfunctions and needed continuous assistance. CONCLUSIONS: Surgical risk factors typical of this age group were identified: cranio-spinal location, damage to the cortical or deep venous system, severe peritumoral edema, and poor neurological preoperative conditions. Systemic risk factors were insulin-dependent diabetes and obesity.

Potential role of in vitro 1H magnetic resonance spectroscopy in the definition of malignancy grading of human neuroepithelial brain tumours.

The increasing sensitivity of neuro-imaging in the diagnosis of brain expanding lesions is not directly related to biopathological specificity and new technological approaches are under study. In particular Magnetic Resonance Spectroscopy (MRS) allows evaluation of some biochemical pathways whose metabolic alterations may be correlated with the nature and malignancy grading of primary brain tumours. In the present study the author performed an in vitro high field 1H MRS (9.4 and 14.1 T) analysis of specimens obtained from stereotactic biopsy or microsurgical removal of primary brain tumours. Different samples derived from heterogeneous areas and/or infiltrated perilesional regions were examined. This study was principally focused on malignancy grading of gliomas and its correlation with the ratio (R) between the resonance band arising from choline containing compounds (between 3.14 and 3.35 ppm) and the total creatine signal (3.0 ppm). Analyses allowed significant discrimination between astrocytomas (R = 2.4 +/- 0.6) and glioblastoma (GBM) (R = 4.4 +/- 1.3) [p < 0.002]; however the results did not allow discrimination between differentiated and anaplastic astrocytomas. The GBM showed the largest spread of values corresponding to their higher level of tissue heterogeneity and de-differentiation. Studies on non astrocytic brain tumours indicated that even higher R values were exhibited by oligodendrogliomas, even in well differentiated forms (p < 0.02 with respect to GBM). Moreover, preliminary observations indicated that signals arising from other metabolites may also contribute to a differential diagnosis of different oncotypes. Among these glycine appears particularly relevant, since higher levels were measured for this amino acid in GBM with respect to both astrocytomas and oligodendrogliomas.

Differentiation of glioblastoma multiforme from astrocytomas by in vitro 1H MRS analysis of human brain tumors.

In vitro high resolution 1H NMR spectroscopy allows non-invasive metabolic evaluation of specimens derived from surgically biopsied or resected brain tumors, with the aim of identifying potential markers of different malignancy grading, and improving diagnostic and therapeutic strategies. In the present study we evaluated 36 patients affected by different brain gliomas (7 well differentiated astrocytomas, 7 anaplastic astrocytomas, 16 glioblastomas, 6 oligodendrogliomas). These analyses allowed discrimination between well differentiated and anaplastic astrocytomas (AII + AA) and glioblastoma multiforme (GM) samples on the basis of the ratio between the integrated choline-containing resonance (b"Cho") and the creatine peaks (creatine (Cr) + Phosphocreatine (PCr)). While no definite difference was found between AII and AA, significantly higher values were observed for this ratio in GM. Other signals, derived from different metabolites, such as Glycine (Gly) and N-acetyl-aspartate (NAA), may also assume relevance in differential tumor diagnosis. In this study an increased [Gly]/[Cr + PCr] ratio was observed in GM with respect to AII and AA. The NAA levels observed in our tumor specimens may be explained on the basis of tumor cell infiltration into brain adjacent tissue. Interesting, but inconclusive, are the data concerning oligodendrogliomas, which, also in well differentiated forms, exhibit increased levels of b"Cho"/(Cr + PCr) ratio. The present study confirms the role of MRS in the biochemical characterization of neoplastic brain tissue and its potential contribution to a better selection of multidisciplinary treatment strategies.

The transdural extension of gliomas.

The extraneural spreading of gliomas is an infrequent occurrence which is not necessarily related to either tumor histology or site. This paper reports two cases, a glioblastoma and an oligodendroglioma, both presenting extradural diffusion. In the first case, where there was severe intracranial hypertension, the tumor found its way out from the neurocranium, far from the site of the operation, perforating the dura and the bone of the cranial base. In the second case, the operation may have facilitated the extraneural invasion. This unusual behaviour of glial tumors is probably less rare than presumed. It may go unnoticed if the attention is concentrated on the usually severe neurological syndrome which is present in these patients.

The role of immunocytochemical assays in the diagnosis of stereotactic biopsies from intracranial tumors.

A selected panel of monoclonal antibodies (MoAbs) directed to distinct tumor associated antigens (TAA) has been tested to define the capability of these reagents to differentiate among metastatic carcinoma, lymphoma and primary brain tumor on cytologic specimens obtained with stereotactic techniques. Results obtained on 50 patients bearing either single or multiple brain lesions demonstrated that immunocytochemical (ICC) methods can distinguish between primary brain tumor and brain metastasis suggesting, in 90% of patients with cryptic primary neoplasia, the site of origin of the tumor.

Lonidamine in the combined treatment of malignant gliomas. A randomized study.

Lonidamine (LND) is a drug that interferes with energy metabolism of cancer cells, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK). In such way LND could impair energy-requiring processes, as recovery from potentially lethal damage, induced by radiation treatment and by some cytotoxic drugs. A randomized study started in November 1983, to evaluate the efficacy of LND in association with radiotherapy as first line treatment in malignant gliomas, after surgical procedure. LND was also used in association with Lomustine (CCNU) at the moment of documented clinical and neuroradiological recurrence. At the present time 60 patients entered the study, and 47 are evaluable. Present preliminary results are not statistically significant, however indicate that LND tends to prolong the median survival time and the rate of one year survivors.

Surgical treatment of paediatric malignant neuroepithelial brain tumors.

The role of the neurosurgeon in dealing with malignant neuroepithelial brain tumors, both supra- and infratentorial, in paediatric age, is stressed; this because surgery is the main therapy, and also it is mandatory, in order to achieve the pathological diagnosis, essential for planning any kind of complementary treatment. Open surgery versus stereotactic biopsy is considered, with emphasis on brain stem tumors. The treatment of malignant tumor recurrencies is also discussed, and the indications of a second surgical look in patients harboring recurrent medulloblastoma is proposed for discussion, when long disease-free time occur and combined modality treatments are performed.

Cystic appearance of meningiomas: considerations on a series of 12 patients.

Twelve patients affected with meningiomas with a fluid component are reviewed. Six presented with intratumoral cysts and 6 with extratumoral fluid collections that in 3 cases were of clear CSF. The formation mechanism of the two types are quite different. Intratumoral cysts are caused by biological changes within the tumor, while the extratumoral ones appear to be secondary to local hydrodynamic changes and CSF reabsorption disturbances. The CT (computerized tomography) scan may be equivocal either for the diagnosis of the meningioma or, once the meningioma is suspected, for identifying the type of cyst involved. The angiography is useful for a correct preoperative diagnosis that, once suspected, can be frequently made.

Mucocele of neurosurgical interest: clinical considerations on five cases.

The authors present five patients with mucocele, submitted to neurosurgery. Two had mucoceles spreading from the frontal and/or the anterior ethmoidal sinuses and had only compressive mass symptoms, either on the ocular globe or on the frontal lobe or on both. Three patients had mucoceles growing from the sphenoid and/or posterior ethmoidal sinuses. In these latter, the mass symptoms were less evident. All the patients suffered excruciating retro-ocular pain and two presented cranial nerve damage. The correct diagnosis in these cases is crucial to avoid a too aggressive treatment since these patients are generally sent to a neurosurgeon for a suspected cranial base malignancy or an invasive pituitary adenoma. The principles of a correct differential diagnosis and of operative treatment are outlined based on an analysis of the literature and the authors experience.

The potential role of lonidamine (LND) in the treatment of malignant glioma. Phase II study.

Up-to-date unsatisfactory results obtained in multimodality treatments of malignant glioma have prompted the research of new therapeutic modalities with 'unconventional' modes of action. Lonidamine (LND) is a drug which reduces aerobic glycolytic activity in both human and experimental tumors. This effect mainly depends on the inhibition of mitochondrially-bound hexokinase (HK) which is present in large amounts in malignant cells. A Phase II study was conducted on patients with recurrent glioma; 12 patients were admitted to the study. Clinical side effects were moderate, necessitating a reduction of the dosage in only 1 case. The objective results were evaluated according to the indications of Levin. 2 responders and 3 cases of stable disease were observed out of 10 evaluable patients. The potential value of this new drug is discussed.

Methodology of stereotactic biopsy.

The great technological improvement in the neurosurgical tools and in the neuroradiological imaging has brought about the diffusion of the stereotactic techniques. They are crucial for the diagnosis and treatment of intracranial expanding lesions of small dimensions or located in sites inaccessible to conventional techniques. The Authors describe the most common systems and methodologies for the stereotactic biopsy. They stress the importance of performing serial explorations which can provide evidence of the heterogeneity of the neoplastic lesion and of the infiltration of the brain adjacent to the tumor.