Assessment of candidate immunohistochemical prognostic markers of meningioma recurrence.

Although tumour recurrence is an important and not infrequent event in meningiomas, predictive immunohistochemical markers have not been identified yet. The aim of this study was to address this clinically relevant problem by systematic retrospective analysis of surgically completely resected meningiomas with and without recurrence, including tumour samples from patients who underwent repeat surgeries. Three established immunohistochemical markers of routine pathological meningioma work-up have been assessed: the proliferative marker Ki-67 (clone Mib1), the tumour suppressor gene p53 and progesterone receptor (PR). All these proteins correlate with the tumour WHO grade, however the predictive value regarding recurrence and progression in tumour grade is unknown. One hundred and fourteen surgical specimens of 70 meningioma patients (16 male and 54 female) in a 16 years' interval have been studied. All tumours had apparently complete surgical removal. On Mib1, PR and p53 immunostained sections, the percentage of labelled tumour cells, the staining intensity and the multiplied values of these parameters (the histoscore) was calculated. Results were statistically correlated with tumour WHO grade, (sub)type, recurrence and progression in WHO grade at subsequent biopsies. Our results confirmed previous findings that the WHO grade is directly proportional to Mib1 and p53 and is inversely proportional to the PR immunostain. We have demonstrated that Mib1 and p53 have a significant correlation with and predictive value of relapse/recurrence irrespective of the histological subtype of the same WHO grade. As a quantitative marker, Mib1 has the best correlation with a percentage of labelled cells, whereas p53 with intensity and histoscore. In conclusion, the immunohistochemical panel of PR, p53, Mib1 in parallel with applying standard diagnostic criteria based on H and E stained sections is sufficient and reliable to predict meningioma recurrence in surgically completely resected tumours.

Cefazolin prophylaxis in neurosurgery monitored by capillary electrophoresis.

Prophylactic use of antibiotics to prevent postoperative infections is a routine method in neurosurgery. Little is known about the period of effectiveness of antibiotics applied only for the purposes of operation. The actual concentration of cefazolin was determined in the serum, in the contents of wound drains, and in the cerebrospinal fluid in a 24-hour postoperative period after the administration of 1 g of cefazolin just prior to skin incision in 8 patients undergoing lumbar discectomy and 11 patients undergoing craniectomy. The concentration of the antibiotic was then compared with the minimal inhibitory concentration values of cefazolin for 10 different bacterial species. For evaluating the concentration of cefazolin, capillary electrophoresis was used, which is a new clinical application of this separation technique. Results showed that the antibiotic was effective against bacterial breeding in the serum and in the drainage up to 12 hours. The drug concentration in the cerebrospinal fluid remained less than the value of the serum, and it exceeded the minimal inhibitory concentration values only for approximately 5 hours.

Posterior interbody fusion using laminectomy bone and transpedicular screw fixation in the treatment of lumbar spondylolisthesis.

BACKGROUND: Laminectomy bone is used widely in posterolateral lumbar fusion, but not interbody fusion. No prospective evaluation of interbody fusion using bone grafts from the posterior neural arch in spondylolisthesis has been found in the literature. We prospectively studied series of patients operated on for lumbar spondylolisthesis to evaluate clinical improvement and bony fusion. METHODS: Forty-six patients were operated on for lumbar spondylolisthesis using a simplified one-stage posterior procedure. The whole mobile dorsal segment of the vertebral arch was taken out in one piece and the bone was used for interbody fusion. Fixation was performed with transpedicular screws and rods using transverse connectors. RESULTS: After an average follow-up time of 27.3 months, 87% of the patients could be considered to have an excellent or good clinical outcome. The rate of successful fusion was 95.7%. No noteworthy complications occurred. CONCLUSION: Laminectomy bone seems to be optimal for posterior interbody fusion and together with transpedicular rigid fixation the long-term clinical and radiological results are convincingly good. The method is advisable even for severe spondylolisthesis.

Expression of invasion-related extracellular matrix molecules in human glioblastoma versus intracerebral lung adenocarcinoma metastasis.

Tumor cell invasion into the surrounding brain tissue is mainly responsible for the failure of radical surgical resection, with tumor recurrence in the form of microdisseminated disease. Extracellular matrix (ECM)-related molecules and their receptors predominantly participate in the invasion process, including cell adhesion to the surrounding microenvironment and cell migration. The extent of infiltration of the healthy brain by malignant tumors strongly depends on the tumor cell type. Malignant gliomas show much more intensive peritumoral invasion than do metastatic tumors. In this study, the mRNA expression of 30 invasion-related molecules (twenty-one ECM components, two related receptors, and seven ECM-related enzymes) was investigated by quantitative reverse transcriptase-polymerase chain reaction. Fresh frozen human tissue samples from glioblastoma (GBM), intracerebral lung adenocarcinoma metastasis, and normal brain were evaluated. Significant differences were established for 24 of the 30 molecules. To confirm our results at the protein level, immunohistochemical analysis of seven molecules was performed (agrin, neurocan, syndecan, versican, matrix metalloproteinase 2 [MMP-2], MMP-9, and hyaluronan). Determining the differences in the levels of invasion-related molecules for tumors of different origins can help to identify the exact molecular mechanisms that facilitate peritumoral infiltration by glioblastoma cells. These results should allow the selection of target molecules for potential chemotherapeutic agents directed against highly invasive malignant gliomas.

Quantitative determination of hyaluronan content in cerebral aneurysms by digital densitometry.

OBJECT: Hyaluronan (HA) is a highly hydrated macromolecule; it is one of the essential components of the extracellular matrix (ECM) of the arteries and plays an important role in maintaining the biomechanical features of blood vessels. Although the potential contribution of HA in aneurysms of different vessels has been studied intensively, no data are available about the alteration of the HA content in the extracellular matrix of intracranial aneurysms. The aim of the study was to determine the hyaluronan content in the wall of human cerebral arteries. METHODS: A biotinylated aggrecan fragment that binds specifically to HA was used to stain samples from cerebral aneurysms (n = 11) to compare the HA content to non-aneurysmal arteries of patients who had intracranial aneurysm (n = 11), and to histologically normal arteries of patients who had expired from non-vascular diseases (n = 14). Digital microscopic densitometry was used for the quantitative analysis of the hyaluronan content in these samples. RESULTS: The highest level (169.5 +/- 7.9) was detected in aneurysms, while the HA-level of non-aneurysmal vessels was lower (130.2 +/- 16.8). Both vessel groups contained significantly higher HA than the normal cerebral arteries (32.9 +/- 2.1). CONCLUSIONS: Results suggest that an elevated hyaluronan level in the extracellular matrix may affect the cerebral arterial wall architecture. It is reasonable to suppose that the increased hyaluronan content creates a viscoelastic ECM which might improve the biomechanical resistance of the thinned vessel wall.

Posterior lumbar interbody fusion (PLIF) using the bony elements of the dorsal spinal segment.

Many different types of surgical technics for treating unstable degenerative spondylolisthesis of the lumbar spine has been reported. The most important part of the different procedures is to achieve a solid bony fusion between the two vertebrae. Authors report a new simple method of posterior lumbar interbody fusion in spondylolisthesis. The whole posterior segment of the mobile neural arch is removed and used for fusion. Corticospongiosus dowels and small bone chips are impacted into the disc space emptied totally before. Monosegmental transpedicular fixateur is required for stability. 33 patients with an average follow up of 20 months showed a clinical improvement of 88%. The radiologically proved fusion rate was 90%. Authors achieved good clinical outcome and high bony fusion rate with the one stage operation from posterior approach for treating lumbar spondylolisthesis.

ODC mRNA as a prognostic factor for predicting recurrence in meningiomas.

In proliferating neoplastic cells, activity of the enzyme ornithine decarboxylase (ODC) increases. Among other brain tumors, ODC activation could also be observed in meningiomas. In the present study, we have investigated ODC gene expression in primary and recurrent meningiomas at the transcriptional level. ODC mRNA (messenger ribonucleic acid), ODC activity, number of mitoses, and Ki-67 index as a marker for nuclear proliferation were quantified in three different groups of meningiomas: tumors without recurrence in a 8.4 years median follow-up period, tumors with recurrence within a median follow-up of 3.0 years, and their corresponding recurrent tumors. ODC mRNA level was significantly higher in meningiomas with later recurrence as compared to meningiomas without recurrence (p < or = 0.01), whereas it declined in the recurrences of the second group (p < or = 0.001). In contrast, ODC activity showed no difference between the two groups of primary tumors, but a significant increase of enzyme activity could be observed in the recurrences as compared to the correponding primary tumors (p < or = 0.001). Likewise, an increase of the Ki-67 index could be detected in the recurrent group (p < or = 0.001). These results suggest that ODC mRNA may represent a prognostic factor for predicting recurrence in meningiomas.