Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and angiogen. VEGF-A protein, which is identical to vascular permeability factor, is a regulator of angiogenesis. In this study, 101 patients with meningiomas, and possible co-factors to PTBE, such as meningioma subtypes and tumor location, were examined. Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p < 0.05). The capillary length in the meningiomas was positively correlated to the PTBE (p = 0.038). If VEGF is responsible for the formation of PTBE, the edema may be treated with the anti-VEGF drug Bevacizumab (Avastin), which has been shown to reduce PTBE in patients with glioblastoma multiforme.

The aim of this work was to study the vascular endothelial growth factor A (VEGF-A) pathway and peritumoral brain edema (PTBE) through comparison of non-angiomatous and angiomatous meningiomas. Meningiomas are common intracranial tumors, which often have PTBE. VEGF-A is an integral part of PTBE formation and angiogenesis, and the capillary-rich angiomatous meningiomas are known for their PTBE. The VEGF-A receptor VEGFR-2 is responsible for the angiogenic effect of VEGF-A on endothelial cells, which is enhanced by the co-receptor neuropilin-1. Forty non-angiomatous, 22 angiomatous meningiomas, and 10 control tissue samples were collected for the study. Magnetic resonance images were available for 40 non-angiomatous and 10 angiomatous meningiomas. Tissue sections were immunostained for CD34, MIB-1, estrogen- and progesterone receptors. ELISA, chemiluminescence, and RT-qPCR were used for VEGF-A, VEGFR-2, and neuropilin-1 protein and mRNA quantification. Angiomatous meningiomas had larger PTBE (695 vs 218 cm(3) , p = 0.0045) and longer capillary length (3614 vs 605 mm/mm(3) , p < 0.0001). VEGF-A mRNA, neuropilin-1 mRNA, and VEGFR-2 protein levels were higher in angiomatous meningiomas independently of the capillary length (p < 0.05). Neuropilin-1 protein levels were lower in angiomatous meningiomas (p < 0.0001). The VEGF-A pathway and tumor capillary length may be essential for PTBE-formation in meningiomas. Further investigations of this pathway could lead to earlier therapy and targeted pharmacological treatment options.

For decades, the preferred and almost sole method for measurement of gene expression has been RT-qPCR. The method is robust, inexpensive, and well-studied; however, PCR is also quite laborious and vulnerable to contamination. As part of an investigation of VEGF-A gene expression in meningiomas, an alternative and less laborious method for gene expression analysis based on branched DNA hybridization and chemiluminescence (Lumistar) was tested. Albeit the two methods differ, in principle, cellular mRNA-concentration is measured with both. Because they both determine gene expression via the measurement of mRNA-concentration, they were expected to be comparable. The aim of the present study was to compare Lumistar to the traditional RT-qPCR approach in a routine laboratory setting, where there is emphasis on rapid analysis response. Meningioma (n = 10) and control brain tissue (n = 5) samples were collected and VEGF-A and GAPDH mRNA were quantified using both RT-qPCR and Lumistar. Furthermore, two dilution series of two of the meningioma samples were prepared in order to make quantitative analyses. Both Lumistar and RT-qPCR-results were found to follow concentration dependent linear paths when diluted (p < 0.0001 and p < 0.01). Finally, Lumistar and RT-qPCR analyses were performed with the inclusion of a reference gene (GAPDH), where similar results were obtained with the two methods (R2 = 0.48; p = 0.01). It is intriguing that in spite of the vast difference in handling and assay principles, gene expression results are similar. The preferred method depends on the variability of the samples, budget, and time. Lumistar was less time consuming, while RT-qPCR was less expensive and best suited for data sets with large sample variability.

Gi respons på artikler gjennom artiklenes kommentarfelt på tidsskriftet.no. Innleggene publiseres fortløpende på Tidsskriftets nettside og et utvalg av innleggene publiseres også i papirutgaven i spalten «Brev til redaktøren». Redaksjonen forbeholder seg retten til å foreta redaksjonelle endringer. Forfattere av vitenskapelige artikler har tilsvarsrett, jf. Vancouver-gruppens regler. I studien var det ikke akupunktur, men lette elektriske støt via nåler plassert i huden, såkalt elektroakupunktur, som ble utført (2). Studien var ikke blindet. Pasientene ble delt i to grupper. Den ene gruppen fikk elektroakupunktur i det som ble identifisert som akupunkturpunkter, den andre fikk nåler uten elektrisitet i andre punkter. Det var med andre ord to variabler som ble byttet mellom gruppene. Flere studier har de siste årene vist at det ikke spiller noen rolle hvor på kroppen akupunkturnålene plasseres (3, 4). Det er derfor rimelig å anta at det er den elektriske stimuleringen som gir effekten som beskrives i artikkelen. Slik transkutan elektrisk stimulering blir ofte beskrevet som akupunktur, men mangler likhetstrekk med klassisk akupunktur, dessuten var nålene tilfeldig plassert på akupunkturpunkter. BREV TIL REDAKTØRENDa det med tiden bare blir tydeligere at jo bedre konstruert studier av akupunktur er, desto mindre og naermere placebo blir effekten. Burde vi ikke da la vaere å anbefale dette som behandling til våre pasienter? Re: Akupunktur mot forstoppelse342Som angitt var akupunktørene ikke blindet (1). Det er da sannsynlig at den sparsomme behandlingseffekten i denne studien kan tilskrives observatørskjevhet. Dette er et velkjent svakt punkt i akupunkturstudier. Studiens størrelse fremheves som et kvalitetsstempel, men feces foredles ikke nødvendigvis av størrelsen.Bør man bruke mer tid på akupunkturstudier på banale tilstander når det allerede finnes flere behandlingsalternativer?Jeg vil be om at man stiller se litt mer kritisk til disse akupunkturstudiene sett i lys av hvor få gode studier det finnes på området og at disse ikke viser noen virkning utover placeboeffekten. La oss bruke tid, ressurser og spalteplass på behandlinger som faktisk hjelper. Damoun Nassehi damoun.nassehi@gmail.comDamoun Nassehi (f. 1979) er allmennlege ved Eigersund kommunale legesenter. Ingen oppgitte interessekonflikter.