Malignant glioma: Should chemotherapy be overthrown by experimental treatments?

Despite more than two decades of clinical research with chemotherapy, the outcome of malignant gliomas remains poor. Recent years have seen major advances in elucidation of the biology of these tumors, which in turn have led to the current development of innovative therapeutic strategies. The question confronting us at the end of the 1990s is whether we should continue to use and investigate chemotherapy or whether the time has come for experimental treatments. As a contribution to this debate, we reviewed the abundant literature on chemotherapy of malignant glioma, paying special attention to methodological features. The new treatment approaches based on current knowledge about glioma biology are then briefly summarized. Assessment of more than 20 years of chemotherapy trials is discouraging despite a few areas of modest success. Only patients with specific histology (oligodendroglioma, anaplastic astrocytoma) and good prognostic factors (young age, good performance status) may benefit from chemotherapy, with a possible reversal of neurological dysfunction. However, the real impact on survival is small (anaplastic astrocytoma) or undefined (oligodendroglioma). Furthermore, it is unfortunately obvious that the outcome of glioblastoma patients is not significantly modified by chemotherapy. We believe the time has come to explore the potential of novel biological therapies in glioblastoma patients. This could also be proposed for anaplastic astrocytoma and oligodendroglioma patients after failure of chemotherap

Double-lumen balloon microcatheter-assisted occlusion of cerebral vessels with coils: a technical note

The purpose of this study was to describe a balloon-assisted double-lumen microcatheter technique to perform a controlled and tight coil packing of a vascular segment for vessel occlusion. This technique can be performed immediately after a test occlusion with the balloon kept in place and was, as illustrated in six cases, in our experience safe, straight forward to use and fas

MGMT gene silencing and benefit from temozolomide in glioblastoma.

BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. RESULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. CONCLUSIONS: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit

Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

Glioblastoma multiforme (GBM) remains the most devastating primary tumour in neuro-oncology. Targeting of the human epithelial receptor type 2 (HER2)-neu receptor by specific antibodies is a recent well-established therapy for breast tumours. Human epithelial receptor type 2/neu is a transmembrane tyrosine/kinase receptor that appears to be important for the regulation of cancer growth. Human epithelial receptor type 2/neu is not expressed in the adult central nervous system, but its expression increases with the degree of astrocytoma anaplasia. The specificity of HER2/neu for tumoral astrocytomas leads us to study in vitro treatment of GBM with anti-HER2/neu antibody. We used human GBM cell lines expressing HER2/neu (A172 express HER2/neu more than U251MG) or not (U87MG) and monoclonal humanised antibody against HER2/neu (Herceptin®). Human epithelial receptor type 2/neu expression was measured by immunohistochemistry and flow cytometry. Direct antibody effect, complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity were evaluated by different cytometric assays. We have shown, for the first time, the ability of anti-HER2/neu antibodies to induce apoptosis and cellular-dependent cytotoxicity of HER2/neu-expressing GBM cell lines. The results decreased from A172 to U251 and were negative for U87MG, in accordance with the decreasing density of HER2/neu receptors

Screening for latent tuberculosis infection among undocumented immigrants in Swiss healthcare centres; a descriptive exploratory study

BACKGROUND: Migration is one of the major causes of tuberculosis in developed countries. Undocumented patients are usually not screened at the border and are not covered by a health insurance increasing their risk of developing the disease unnoticed. Urban health centres could help identify this population at risk. The objective of this study is to assess the prevalence of latent tuberculosis infection (LTBI) and adherence to preventive treatment in a population of undocumented immigrant patients. METHODS: All consecutive undocumented patients that visited two urban healthcare centres for vulnerable populations in Lausanne, Switzerland for the first time were offered tuberculosis screening with an interferon-gamma assay. Preventive treatment was offered if indicated. Adherence to treatment was evaluated monthly over a nine month period. RESULTS: Of the 161 participants, 131 (81.4%) agreed to screening and 125 had complete examinations. Twenty-four of the 125 patients (19.2%; CI95% 12.7;27.2) had positive interferon-gamma assay results, two of which had active tuberculosis. Only five patients with LTBI completed full preventive treatments. Five others initiated the treatment but did not follow through. CONCLUSION: Screening for tuberculosis infection in this hard-to-reach population is feasible in dedicated urban clinics, and the prevalence of LTBI is high in this vulnerable population. However, the low adherence to treatment is an important public health concern, and new strategies are needed to address this problem

Total intravenous anesthesia with propofol for burst suppression in cerebral aneurysm surgery: preliminary report of 42 patients

Forty-two patients underwent cerebral aneurysm clipping at our institution in 1991, 35 with a ruptured aneurysm and 7 with an unruptured aneurysm. Preoperatively, 22 patients with a ruptured aneurysm were graded I or II according to the World Federation of Neurosurgical Societies and 21 underwent an operation on the first day. All underwent a standard cerebral protective general anesthesia, combining propofol with fentanyl, arterial normotension (mild hypertension with volume loading and/or dopamine during temporary clipping and once the aneurysm was secured), normocarbia or slight hypocarbia, brain relaxation with lumbar drainage, mannitol and propofol, and electroencephalogram burst suppression when temporary clipping (> or = 2 min) was required. Propofol doses for induction were 1.8 +/- 0.1 mg/kg (mean +/- standard error); for maintenance, doses were 86 +/- 3.5 micrograms/kg per min; and for burst suppression doses were 500 micrograms/kg per min. After clipping, the propofol dose rate was reduced to allow early recovery and neurological examination in the operating room. In 21 patients, temporary clipping was required for a mean duration of 8.8 +/- 1.3 minutes (range, 2-29); none of these patients deteriorated as compared with their preoperative neurological state. Twenty-four of the 42 patients (57%) had a Glasgow Coma Outcome Scale (GOS) score of 1, 7 patients had a GOS score of 2, 8 had a score of 3, and 3 had a score of 5. Thirty-two patients were extubated in the operating room with a mean GOS Score of 13.2 +/- 0.5, and 10 were extubated later in the intensive care unit.(ABSTRACT TRUNCATED AT 250 WORDS

[Hypodensities accompanying various meningiomas in x-ray computed tomography]

This is a review of 80 cases of intracranial meningiomas, which were operated on in the neurosurgical Service of Lausanne. 51 tumors were associated with an area of low attenuation of variable extension on the CT-scan. In 49 of these, the low attenuation areas corresponded to oedema. In two of them a cyst was discovered at operation. One was a subarachnoid cyst and the other one was an intracerebral cyst separated from the tumor by a thin layer of cerebral cortex. A correlation was attempted between these areas of low attenuation and the clinical history, the CT-scan characteristics, the location, the macroscopic appearance at operation and the histology of the tumors. From these data, the typical features of a meningioma more likely to be associated with an area of low attenuation on the CT-scan were determined. This tumor is often located in the subfrontal area or in the middle base of the skull, and epilepsy or increased intracranial pressure are more likely to be present. The most common histological type is syncytial

Distribution of GABA-containing neurons in human frontal cortex: a quantitative immunocytochemical study

Fresh biopsy specimens of human cerebral cortex were collected from patients suffering from deep-seated tumors requiring resection. GABAergic neurons were revealed in 50-microns-thick sections, for pre-embedding, and 1-micron-thick sections, for post-embedding GABA immunocytochemistry. In both thick and thin sections, the reaction product was found in neuronal cell bodies and in small profiles in the neuropil. In both preparations, GABA-containing somata were distributed evenly throughout the depth of the cortex. As best appreciated in the thicker sections, GABA-immunoreactive neurons belonged to a variety of morphological cell types with multipolar, bitufted or bipolar, and horizontal dendritic arbors. In the semi-thin sections sampled in the frontal cortex, the proportion of these neurons could be accurately evaluated and was found to be 21.2% +/- 4.8% of all cortical neurons. The average size of GABA-immunoreactive neurons was, in each layer, smaller than that of immunonegative neurons. The average soma size of both neuronal populations, immunoreactive and immunonegative for GABA, increased with depth. The comparison between the rat, cat, macaque monkey, and human GABAergic interneurons revealed similarities among primate brains, contrasting with the parameters (morphology, size, density) measured in rodents. These data are pertinent to the involvement of the GABAergic neurons in the shaping of receptive-field properties of cortical neurons in healthy brains and in pathologies involving the impairment of inhibitory neurotransmission