| Study background and purposeSince Dr. Leksell adopted the stereotaxis to treat a patient with an intracranial tumor, thousands of people had undertaken this new measure. Among of the stereoscopic directional radiosurgery (SRS), Gamma knife radiosurgery attracted the most intention from doctors.In recent years, Gamma knife has become a good auxiliary means to the traditional neurosurgery. Meanwhile, more and more attention has also been paid on the related radiation damage,which was characterized as a brain edema.The peritumoral brain edema, which was brought about by Gamma knife treatment, greatly limited the extensive use of Gamma knife in clinical surgeries.The mechanism for peritumoral brain edema after Gamma knife radiosurgery could be investigated through discussions about the pathologic changes after stereotactic radiosurgery (SRS), which was characterized as a brain edema mainly. It will be also helpful for doctors to reduce the complications after Gamma knife radiosurgery.In recent years, reports about brain edema induced by the.SRS were not rare. But the real pathologic mechanism remained unclear.Dr. Levin discovered that the single radiation with a big dosage was different from the conventional external radiation. This management could stimulate body to release some vasoactive substances (such as histamine and slow-reaction substance of anaphylaxis, etc) and these substances might increase the ventilation of blood vessels.In addition, the single radiation with a big dosage might also induce the occurrence of vasculitis. Thus, the blood flow within the tumor might increase consequently and the brain edema could be aggravated.Dr. Rubin found that injury of endothelial cell and blood-brain barrier closely related to the radiation injury, or might initiate this procedure.Additionally, some scientists believed the interference of venous return induced by the injury of cortical vein, toxic reaction after tumor necrosis and demyelination of white substance might also contribute to SRS-related brain edema.The current study is trying to observe the ultrastructural characteristics of the blood brain barrier and the immunity histochemistry change of the tumors and brain tissues around tumors, which had undergone the gamma knife. In this way, the mechanism of intractable peritumoral cerebral edema after Gamma knife radiosurgery could be investigated.Materials and methodsObject18 patients with cranial tumor were enrolled into this study. Among of these patients, 11 were male and 7 were female. They ranged from 29 to 71 years old and the average age was 41. 8.The location and classification of tumors were as follows. 4 cases were meningioma aside cerebral falx. 3 cases suffered from parasagittal meningioma. 2 cases had sphenoid ridge meningioma, 2 cases were left frontal-parietal lobe glioma, 1 case was right frontal-parietal lobe glioma, 3 cases were left frontal-parietal metastatic tumor (MT), 1 case was right frontal MT, .1 case was Hippel-Lindan syndrome, and the other one case was acoustic neurilemoma.MethodsAll patients suffered from a severe peritumoral brain edema since 3 to 13 months after the gamma knife treatment. Managements including mannitol, furosemide and metasolon proved to be invalid. Then the excision including tumors and gliosis tissues was performed.During the operation, the samples of brain edema tissue were taken at the tumor center, edge of the tumor and 1lmm~20mm sites around the tumor, respectively. Then, histology, immunohistochemistry and transmission electron microscope examinations were made on all these samples.ResultsFirstly, the examination of smears by naked eyes was as follows. The color of the brain tissue in meningioma differed from grey color to dust color. The tumor tissue was very tough and the margin of it was clear. Contrasted to it, the brain tissue of astrocye tumors looked grey to red. The tissues between tumors and normal tissues around tumors were very tough with a relatively clear margin. The adherence was close. As for the metastatic tumors, tissue presented with a prunosus color and a moderate toughness with a clear margin. The tissue of acoustic neurilemoma looked madder red and the quality was flexible with a well defined margin. The tumor tissue of angioreticuloma was grey-white and tough with a well- defined margin. The inflexibility of tumor blood vessels was very poor. Vessel walls were thickened and lumens became thinner. Adhesion canbe found partly and liquefactive necrosis can be found at the center of tumors.Secondly, the examination results of optical lens were recorded as follows.Similar radiation injury changes with different degrees were observed at all the cases in this study. The structure of tumor cells at the tumor center disappeared, whereas lots of cell fragments remained at the edge of center areas. The structure of blood vessels looked like coats of onions. Swelled cells, enlarged cells and puffed endocylema were found at the edge of brain tumors. Hyaline degeneration can be also found. Some tumor cells died and decreased. Small blood vessels were dilated and hyperemia as well, as hyaline degeneration. The walls of blood vessel were thickened and lumen narrowed. Some inflammatory cell infiltrated. The small blood vessels around the brain tumor tissues dilated and became hyperemia. Pyramidal cells and colloid cells looked like hypoxia oedema. Degeneration of nucleus was found and the nucleoli disappeared with a dense stain.Thirdly, the immunohistochemistry examination results were as follows. As for the GFAP stain, 8 cases had a positiveexpression more than 10 %, although with a relatively low degree. The negative results were found in the other 10 cases. For the VEGF stain, 6 cases had a positive expression more than 5 %, but with a low degree. The negative results were found in 12 cases. For the PCNA stain, 6 cases had a positive expression. Among the six cases with positive results, the expression in five cases was less than 1 %, and the other one was 11. 3%. The negative results were found in the other 12 cases.Fourthly, the results of electron microscope were recorded as follows. Most of capillary endothelial cells in tumors and brain tissues around tumors became flatter and thinner than usual. Some of them crinkled with many small openings on the surface of cell bodies. The gaps between the tight junctions of endothelial cells became wider and some of the tight junctions were broken. The number of phagolysosome in the intracelluar matrix increased. The basal membranes around the blood vessels became thinner obviously. The gelatinous constituted by the end-feet of horizontal cells turned thinner and some of these gelatinous were lacking. Chondriosomes of astrocytes swelled and cristae decreased or disappeared. The obvious tumor necrosis can be found in the tumor tissues. The caryocinesia were very rare. Proliferation of the fibrousconnective tissue and the endomembrane of minute blood vessels were observed. In addition, elastic fibers swelled and collapsed.ConclusionsIntractable peritumoral brain edema after gamma knife radiosurgery is a kind of radiation brain injury, which occurred after the Gamma knife treatment. The mechanism of this brain edema is special. The following factors might contribute to the occurrence of this complication.First, three layers of blood- brain barrier were destroyed in different degrees, which was considered as the main pathological basis for the intractable peritumoral brain edema.Second, the recovery function of blood-brain barrier lost as a result of the injury of astrocytes. The irreversible injury of blood-brain barrier played an important role in the refractoriness of brain edema.Third, the wall of the minute vessels of tumors thickened andthe lumens narrowed gradually. Subsequently, the venous return of brain tumors was hindered. Thus, the brain edema was aggravated. |
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