[Intraoperative vascular fluorescence in cerebral glioblastomas and vascular histological features]. / Intraoperatsionnaia fluorestsentsiia sosudov v strukture glioblastom golovnogo mozga i ikh gistologicheskaia kharakteristika.

5-ALA intraoperative fluorescence is widely used in surgery of brain tumors for intraoperative demarcation of boundaries and more total resection because 5-ALA metabolites are not accumulated in the intact brain and vascular tissues. Given this fact, it was hypothesized that fluorescence of vessels in the immediate vicinity of a brain tumor may indicate their infiltration by tumor cells as a potential pathway for their dissemination and as a factor for continued tumor growth after surgery and adjuvant therapy. PURPOSE: Identification of fluorescent vessels located near cerebral gliomas, with a histological description of their structure, relationships with the tumor, and potential invasion of the walls by tumor cells. MATERIAL AND METHODS: A prospective cohort study included 14 patients with malignant supratentorial gliomas, aged 20 to 78 years. Five patients were operated on due to continued tumor growth. Two hours before surgery, all patients received 5-ALA orally. During surgery, a microscope (Carl Zeiss OPMI Pentero, Germany) with a fluorescent module (BLUE-400) was used. In all cases, molecular-genetic and immunohistochemical examinations of the tumor material were performed. During surgery, fluorescent vessels, after evaluating their functional significance, were also resected for histological examination. RESULTS: Glioblastoma and anaplastic astrocytoma were verified in 10 and 4 patients, respectively. In 4 out of 10 glioblastoma cases, vessels with homogeneous or fragmentary fluorescent walls were detected in the tumor bed after resection of most of the tumor; in patients with anaplastic astrocytomas, vascular fluorescence was not observed. In the four vascular samples with intraoperatively detected wall fluorescence, tumor invasion into the vascular layers was revealed in all cases. These patients underwent an immunohistochemical examination with monoclonal antibodies to the glial GFAP marker, which clearly identified areas of ingrowth of tumor cells into the vascular wall. CONCLUSION: 5-ALA intraoperative fluorescence is a fundamentally new approach in the rapid diagnosis of tumor-infiltrated blood vessels. Invasion of tumor cells to intact vessels may be a mechanism of tumor progression and dissemination. Additional resection of fluorescent vessels may affect the radicalness of surgical treatment, but requires a mandatory assessment of their functional significance.

[Intraoperative fluorescence diagnostics in surgery of intracranial meningiomas: analysis of 101 cases]. / Intraoperatsionnaia fluorestsentnaia diagnostika v khirurgii intrakranial'nykh meningiom: analiz 101 nabliudeniia.

Fluorescence diagnostics has been extensively applied in surgery of malignant brain gliomas. However, the use of this technique in surgery of intracranial meningiomas has remained controversial. OBJECTIVE: The study objective was to assess the sensitivity of 5-aminolevulinic acid-based (5-ALA) fluorescence diagnostics in surgery of brain meningiomas and to clarify the clinical and biological factors that may influence the fluorescent effect. MATERIAL AND METHODS: The study consistently included 101 patients with intracranial meningiomas of various locations who were operated on using 5-ALA. There were 28 (27.72%) males and 73 (72.27%) females (median age, 54 years). In all patients, surgery was performed using an operating microscope equipped with a fluorescent module; in 24 of these, laser spectroscopy was used. For comparison of chances to observe the fluorescent effect of 5-ALA in patients having meningiomas with different WHO histological grades (Grade I vs Grade II-III), we performed a meta-analysis that included 10 studies (the largest series) on outcomes of surgical treatment of meningiomas using intraoperative fluorescence diagnostics. RESULTS: Of 101 patients included in this series, observable fluorescence was detected in 95 (94.1%) patients: weak fluorescence in 12 (11.9%), moderate fluorescence in 23 (22.8%) cases, and strong fluorescence in 60 (59.4%) patients. There was no statistically significant relationship (p>0.05) between the rate and intensity of observable fluorescence and the tumor growth pattern (primary/continued), location, WHO grade of malignancy, and histological subtype. In the absence of intraoperative bleeding, tumor fluorescence was statistically significantly brighter (p=0.02). Of 26 patients with hyperostosis, bone fluorescence was observed in 11 (42.3%) cases. There was no statistically significant relationship between administration of dexamethasone, its dose, administration of anticonvulsants, gastrointestinal tract diseases, as well as diabetes mellitus and the fluorescence intensity. There was also no significant relationship between the extent of tumor resection (Simpson scale) and the presence of fluorescence as well as its intensity. Comparison of the observable fluorescence intensity and the laser spectroscopy indicators revealed a significant correlation (r=0.75; p=0.005). CONCLUSION: Meningioma is a well fluorescent tumor, with the technique sensitivity being 94.1%. In some cases, the use of fluorescence diagnostics in surgery of meningiomas improves identification of residual tumor fragments and enables correction of a surgical approach. To assess the effect of fluorescence diagnostics on the recurrence rate and disease-free duration, further research is required.

[Connexin-43 antibodies in intraoperative diagnosis of experimental poorly differentiated gliomas].

Fluorescent diagnosis was first proposed in the early XX century and has been used in neurosurgery for about 15 years. The method relies on selective accumulation of strongly fluorescent protoporphyrin IX in tumor cells. Over the past years, the method of intraoperative fluorescence diagnosis has occupied its niche in many neurosurgical clinics around the world and is now used for fast intraoperative diagnosis in brain tumor surgery. However, the efficiency of fluorescent intraoperative diagnosis using 5-aminolevulinic acid is 80-90% and 58.8% for surgery of Grade III-IV and I-II gliomas, respectively. One of the methods to improve the efficiency of fluorescent diagnosis is to use vector systems for delivering fluorescent drugs into the tumor. This paper reports the results of an experimental study of systems for delivering fluorescent agents (protoporphyrin IX, Alexa 488, Alexa 660) using connexin-43 antibodies in rats with transplanted C6 glioma.

[Intraoperative fluorescence diagnostics upon recurrent operations for brain gliomas].

UNLABELLED: The method of fluorescent diagnosis (FD) using 5-ALA has been widely employed in surgery of primary intracerebral tumors over the last years. The issue of FD application in surgery of gliomas with continued growth has remained less studied. OBJECTIVE: To investigate the efficacy of using FD with 5-ALA and laser spectral analysis in surgery of brain gliomas with continued growth. MATERIAL AND METHODS: 19 patients with Grade II-IV (WHO) gliomas with continued growth of different localization were studied. All tumors localized supratentorially. 5-Aminolevulinic acid hydrochloride "Alasens" (SSC "NIOPIK", Moscow, Russia) was used in the study. The equipment used during surgery included an operating microscope with an attachment for fluorescent navigation. Apart from expert qualitative assessment of a fluorescence extent, computer analysis of the fluorescence and light scattering (diffuse reflection) spectra was performed on a LESA-01-BIOSPEK spectrum analyzer (Russia). RESULTS: Detectable fluorescence was obtained in all the cases. PP IX fluorescence indices from 9.05 to 53.97 (the study was conducted in 12 cases) were determined by quantitative analysis of the spectrograms. The analysis of light scattering revealed its inverse relationship with respect to the fluorescence index. High sensitivity of the method in surgery of gliomas with continued growth requires clarification of method specificity because non-specific accumulation of PP IX in the area of post-radiation necrosis may occur in these patients. CONCLUSIONS: The FD method can be used for intraoperative demarcation of tumor resection boundaries in surgery of cerebral gliomas with continued growth. However, it is necessary to be critical of the high sensitivity of the method in patients with postradiation pathomorphism due to possible non-specific accumulation of PP IX in tissues. A light scattering study may provide additional information about the structure of tissues in the surgical wound.

[Intraoperative combined spectroscopy (optical biopsy) of cerebral gliomas]. / Intraoperatsionnaia kombinirovannaia spektroskopiia (opti-cheskaia biopsiia) gliom golovnogo mozga.

Clinical studies have revealed high selectivity of 5-ALA-induced protoporphyrin IX accumulation in different brain tumors. Modern methods of evaluation of tissues visible fluorescence are based on the qualitative analysis of the images. Up-to-date methods of combined spectral analysis allow fulfilling the intraoperative quantitative evaluation of the protoporphyrin IX content, as well as the scattering and absorption properties of a tissue. This paper presents a new method of the simultaneous analysis of hemoglobin concentration in oxygenated and reduced forms, tumor marker concentration (5-ALA-induced PP IX) and a new way to analyze the changes in the scattering properties of the tissues. The method is implemented by splitting the visible spectrum into intervals where hemoglobin and protoporphyrin IX have the characteristic peaks of absorption and fluorescence. The present method shows the dependence of the fluorescence index from the tumor grade. Combined spectroscopy (optical biopsy) can detect the differences between the subtypes of gliomas that are similar in the protoporphyrin IX fluorescence index. This method complements and enhances the diagnostic capabilities of spectroscopy, which is particularly important in the non-fluorescent glioma surgery.

[Intraoperative fluorescent visualization and laser spectrosopy in intrinsic brain tumor surgery].

Absence of well-defined borders of the glial tumor due to their infiltrative growth is one of the main issues in neurosurgery. A number of methods for intraoperative visualization are available today. The fluorescent metabolic navigation with 5-aminolevulinic acid (5-ALA) combined with quantitative laser spectroscopy is one of the latest technique. In our series of 99 consecutive patients with brain gliomas (WHO Grade I-IV) we found that visible fluorescence was observed in 68% of cases. Additional use of the laser spectroscopy could increase method sensitivity up to 74% due to accumulation of the protoporphyrine IX in nonfluorescense tumors. It was shown that there are some differences in quantitative fluorescence not only within same tumor (glioblastoma) but also in-between low- and high-grade gliomas. Intraoperative fluorescence and laser spectroscopy are effective and very helpful methods of intraoperative imaging in of intrinsic brain tumor surgery.

[First experience of photodynamic diagnosis and laser spectroalanysis in surgery of intracranial meningiomas].

Photodynamic diagnosis (PDD) has been actively implemented into neurooncological practice, especially in cerebral gliomas surgery. This paper describes our first experience of PDD combined with laser spectroanalysis in intracranial meningiomas. The study included 21 patients (8 male and 13 female patients, mean age was 58 years, range--between 37 and 74 years) with intracranial meningiomas operated with PDD in Burdenko Neurosurgical Institute between 2008 and 2011. In 14 cases laser spectroanalysis was used. Tumor fluorescence was present in all but one cases (95%). Spectroanalysis demonstrated that peaks of fluorescence varied between 5 and 46 (mean level was 18.5). These data correlated with visual impression of fluorescence and confirmed that meningioma is a tumor with bright fluorescence. Radical removal (Simpson grade I-II) was achieved in 10 cases, subtotal resection was performed in the rest of the patients. Application of PDD and laser spectroanalysis allows gaining complete information about accumulation of photosensibilizer in the tissue. To our opinion, these methods may be the most useful for determination of the borders of dural and bony invasion which directly affects the surgical tactics and degree of radical removal. Further studies are needed to evaluate the influence of PDD and laser spectroanalysis on long-term surgical outcomes.

[Photodynamic diagnosis and laser biospectroscopy as an intraoperative guidance in neurosurgery].

Different techniques are used today in neurosurgery for intraoperative navigation, including metabolic guidance using 5-aminolevulinic acid (5-ALA). The article focuses on history of intraoperative photodynamic diagnosis (PDD), mechanisms of 5-ALA action, possibilities of its application in different areas of neurosurgery. In addition to visual assessment of fluorescence, laser biospectroscopy significantly increases the diagnostic value of PDD. Laser biospectroanalysis is described in details, wide perspectives of its application in neurosurgery are demonstrated.