[Intraoperative photodynamic therapy in complex treatment of malignant gliomas]. / Primenenie intraoperatsionnoi fotodinamicheskoi terapii v strukture kompleksnogo lecheniya zlokachestvennykh gliom.

Treatment of malignant gliomas is an extremely difficult objective associated with difficult choice of correct strategy. Photodynamic therapy is still not the treatment standard in these patients although this approach significantly improves treatment outcomes in surgery of gliomas. OBJECTIVE: To demonstrate the possibilities of chlorin e6-mediated photodynamic therapy for malignant glial tumors. MATERIAL AND METHODS: There were 161 patients with malignant supratentorial glial tumors who were treated at the Polenov Russian Neurosurgery Institute between 2009 and 2016. Eighty patients comprised the main group (photodynamic therapy), 81 ones - control group (without photodynamic therapy). RESULTS: Photodynamic therapy in complex treatment of malignant brain gliomas significantly increases overall survival in patients with Grade III gliomas up to 39.1±5.5 months (control group - 22.8±3.3 months) and Grade IV gliomas up to 20.7±4.7 months (control group - 13.5±2.3 months) (p=0.0002). This method also increases relapse-free period in patients with Grade III gliomas up to 21.7±3.4 months (control group - 15.8±3.1 months) (p=0.0002) and Grade IV gliomas up to 11.1±2.1 months (control group - 8.0±2.3 months) (p=0.0001).

[Comparative analysis of 5-ALA and chlorin E6 fluorescence-guided navigation in malignant glioma surgery]. / Sravnitel'nyi analiz fluorestsentnoi navigatsii v khirurgii zlokachestvennykh gliom s ispol'zovaniem 5-ALA i khlorina E6.

OBJECTIVE: To analyze specificity and sensitivity of 5-ALA and chlorin E6 fluorescence-guided navigation in malignant glioma surgery. MATERIAL AND METHODS: Fluorescence-guided navigation was analyzed in 50 patients (2 groups) with high-grade glioma. All patients were treated at the Polenov Russian Neurosurgery Institute. Chlorin E6 1 mg/kg intravenously (Photoditazin) was used as a fluorescence inducer in 25 patients (the 1st group), 5-ALA 20 mg/kg orally (Alasens) - in other 25 patients (the 2nd group). Each group included 10 patients with glioma grade III and 15 patients with glioma grade IV. Both groups were statistically representative (p>0.05). RESULTS: In patients with glioma grade III, sensitivity of chlorin E6 fluorescence-guided navigation was 83.8%, 5-ALA fluorescence - 82.5%. Specificity was 66.7% and 64.1%, respectively. In patients with glioma grade IV, sensitivity was 87.7% for chlorin E6 and 88.3% for 5-ALA. Specificity was 85.2% and 88.1%, respectively. CONCLUSION: Statistical analysis confirmed comparable high efficacy of both agents in surgery of malignant gliomas. Sensitivity and specificity of fluorescence-guided navigation with chlorin E6 and 5-ALA were similar (p>0.05).

[Morphological evaluation of the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas]. / Morfologicheskaya otsenka effektivnosti fluorestsentnoi navigatsii s khlorinom e6 v khirurgii zlokachestvennykh gliom.

OBJECTIVE: To evaluate the effectiveness of fluorescence navigation with chlorin e6 in surgery for malignant gliomas based on surgical material morphological and immunohistochemical data. MATERIAL AND METHODS: The surgical material obtained from patients with high-grade (Grade III-IV) anaplastic glioma was examined. Along with histological examination, the proliferation marker Ki-67, the cell cycle transcription factor protein p53, and vascular endothelial growth factor (VEGF) were determined. RESULTS: A significant direct correlation was found between the expression of Ki-67, p53, and VEGF and the fluorescence intensity of tumor tissues (p<0.05). CONCLUSION: The technique of fluorescence navigation using chlorin e6 in comparative morphopathological analysis has confirmed its effectiveness in surgery for malignant gliomas.

[Intraoperative fluorescence control with chlorin E6 in resection of glial brain tumors]. / Rezul'taty ispol'zovaniya intraoperatsionnogo flyuorestsentnogo kontrolya s khlorinom E6 pri rezektsii glial'nykh opukholei golovnogo mozga.

In recent years, fluorescence navigation has been increasingly used in surgery for gliomas. In most studies, 5-ALA derivatives are used as fluorescence inducers. However, there are few data regarding E6 chlorin for these purposes. OBJECTIVE: To evaluate an effectiveness and feasibility of fluorescence navigation with chlorin E6 in surgery of brain gliomas. MATERIAL AND METHODS: The study included 30 patients with glial brain tumors grade II-IV. All patients were operated at the Polenov Russian Neurosurgical Institute. We used surgical microscope (Leica OHS-1), D-Light AF System (Karl Storz, Germany), original fluorescence module (St. Petersburg LOMO, developed by G.V. Papayan) and special software RSS Cam - Endo 1.4.313 for visual analysis of fluorescence. Histological examination included hematoxylin-eosin staining of specimens and immunohistochemical studies. RESULTS: Fluorescence was weak in all patients with Grade II gliomas and strong in almost all patients with Grade III-IV gliomas. Sensitivity of fluorescence diagnosis with chlorin E6 was 72.2% for Grade II gliomas, 83.8% for Grade III gliomas and 87.7% for Grade IV. Specificity of this method was 60% for Grade II gliomas, 66.7% for Grade III gliomas and 85.2% for Grade IV. CONCLUSION: Certain method of fluorescence imaging ensured resection of glial brain tumors using chlorin E6. Intensity of tumor fluorescence correlated with glioma malignancy grade. These results indicate that chlorin E6 is an effective photosensitizer for intraoperative fluorescence diagnosis in surgery for glioma.

[Complex treatment of a patient with neurofibromatosis type 2]. / Kompleksnoe lechenie patsienta s neirofibromatozom 2-go tipa.

Neurofibromatosis type 2, a rare disease, the most characteristic manifestation of which is the presence of bilateral vestibular schwannomas, less often schwannomas of other cranial, spinal and peripheral nerves. Much less frequent are meningiomas (intracranial, including meningiomas of the optic nerves, and spinal), epindymomas and gliomas. As a rule, in one patient several formations occur simultaneously, which creates a certain difficulty in treatment tactics. The authors present a case of type 2 neurofibromatosis in a 22-year-old female patient with multiple schwannomas of spinal roots and an atypical intraventricular meningioma.

Tolerance in the absence of autoantigen.

Regulatory T (T(reg)) cells show promise for treating autoimmune diseases, but their induction to elevated potency has been problematic when the most optimally derived cells are from diseased animals. To circumvent reliance on auto-antigen reactive T(reg) cells, stimulation to vaccine antigens (Ags) may offer a viable alternative while maintaining potency to protect against proinflammatory diseases. Our Salmonella vaccine expressing colonization factor Ag I (CFA/I) possesses anti-inflammatory properties, evident by elevated Th2 cell responses, reduced inflammatory cell infiltrates in the Peyer's patches, and an absence of proinflammatory cytokine production by infected macrophages. Given these findings, we hypothesized whether this vaccine would be protective against experimental autoimmune encephalomyelitis (EAE). As such, Salmonella-CFA/I protected in both prophylactic and therapeutic paradigms against proteolipid protein (PLP(139-151))-mediated EAE in SJL mice. The protected mice showed significantly reduced clinical disease and subsequent resolution when compared to PBS-treated controls. Histopathological studies showed reduced demyelination and no inflammation of spinal cords when compared to PBS- or Salmonella vector-treated mice. To ascertain whether the observed immune deviation was in part supported by T(reg) cells, analysis revealed involvement of FoxP3(+) CD25(+) CD4(+) T cells. Adoptive transfer of induced TGF-beta (+) T(reg) cells from vaccinated mice showed complete protection against PLP(139-151) challenge, but not by naive T(reg) cells. Partial protection to EAE was also achieved by the adoptive transfer of CD25(-) CD4(+) T cells, suggesting that Th2 cells also contributed. Thus, these data show that T(reg) cells are induced by oral vaccination with Salmonella-CFA/I contributing to the efficacious treatment of autoimmune disease.