Associations of IL17A G-197A single nucleotide polymorphism with immunological parameters and structural changes of the brain in schizophrenia

Schizophrenia is a chronic mental disorder that is caused by a complex palette of genetic, epigenetic and environmental factors. Some of the important components of its pathogenesis are systemic inflammation and the dysfunction of immunity, which lead to neuroinflammation, contributing to development of structural brain changes. Earlier we have shown that increase in interleukin-17A levels is associated with morphometric changes and immune dysregulation in schizophrenia. IL17A G-197A (rs2275913) genetic polymorphism is involved in determining interleukin-17A secretion. The goal of this work was to investigate the associations between rs2275913 polymorphism, immune disorders and structural neurovisualization findings in schizophrenia to provide new insights into the immunopathogenesis of this disease. 60 patients aged 18 to 42 years diagnosed with schizophrenia were enrolled. 85 healthy volunteers were included into the control group. Multiplex assay was used to determine cytokine and chemokine serum levels. Rs2275913 polymorphism was assessed by polymerase chain reaction with electrophoretic detection of amplification products. A number of relationships between rs2275913 polymorphism and the immune parameters in schizophrenia were revealed. Carriers of G allele showed significant increase in IFNY, a key cytokine of Th1-link of adaptive immunity, and IL-8, an inflammatory chemokine. Also, increased levels of CXCL16 were observed in patients carrying the G allele. CXCL16 activates secretion of other proinflammatory chemokines and is involved in activation of Th1 adaptive immunity. Associations of heterozygous GA genotype with reduced cortical thickness in a number of areas of the frontal cortex in schizophrenia were found. Changes in cortical thickness in some of these areas, including middle frontal gyrus and orbitofrontal cortex, can be relevant to the pathogenesis of schizophrenia. The results highlight the importance of immunogenetic factors in the pathogenesis of schizophrenia and indicate that the rs2275913 polymorphism requires further studies as a potential biomarker of immune dysregulation and morphometric brain changes in schizophrenia

Association of IL-17A levels with immuneinflammatory profile and structural MRI data in patients with schizophrenia

IL-17A is a proinflammatory cytokine involved in pathogenesis of some neuroinflammatory diseases of the brain. However, its role in schizophrenia is poorly understood. Currently, noninvasive neuroimaging techniques are widely used to assess abnormalities in brain morphology and interactions of neuronal networks in schizophrenia. The aim of this work was to study associations between IL-17A level and brain morphometric parameters in schizophrenia, in order to clarify immune factors of pathogenesis and search for biomarkers of unfavorable disease course. 45 patients with schizophrenia and 30 healthy volunteers were included into the study. The levels of cytokines (IL-5, IL-6, IL-8, IL-10, IL-17A) and inflammatory markers were determined by ELISA or multiplex analysis. MRI scans were performed with a Siemens Magnetom Verio 3T MRI scanner. We used Kruskal–Wallis test to assess significant differences in immunological parameters followed by Mann–Whitney paired comparison; Student test to assess the significance of differences in morphometric parameters of the brain; Fisher exact test to assess the differences in discrete variables, with the differences considered statistically significant at p < 0.05. IL-17A levels were found to be increased in schizophrenia. Its elevated content was associated with increased levels of C-reactive protein, IL-5, IL-6, IL-8, IL-10, and the presence of morphometric changes of frontal and temporal cortex in the patients. So far, the relationships between IL-17A levels, immunoinflammatory parameters and structural brain changes have not been studied in schizophrenia. In the present work, we found an association of elevated IL-17A levels with decreased cortical thickness in several brain regions, systemic inflammation and activation of Th2-link of adaptive immunity in the patients with schizophrenia. According to the literature, a number of brain areas, where cortical thickness was associated with IL-17A levels may be relevant to pathogenesis of the disease and, in particular, to the development of negative symptoms, including impoverishment of interests, speech, and emotions. The results are important for understanding the role of immune disorders in pathogenesis of schizophrenia, including structural changes of the brain, and suggest that IL-17A may be a biomarker of these disorders. Confirmation of associations between structural neuroimaging findings, laboratory markers of inflammation and immune disorders may provide the basis for new multidisciplinary approaches to the diagnosis and prognosis of schizophrenia

A METHOD FOR RESTORING ORAL CAVITY AND TONGUE USING A COMPOSITE, FREE, CHIMERIC, REVASCULARIZED, REINNERVED, MUSCULOCUTANEOUS FLAP AFTER TOTAL GLOSSECTOMY

Background. Combination therapy is the main method used for treatment of patients with locally advanced cancer of the oral floor and tongue. Radical surgery is a key stage of this therapy. These surgeries are inevitably associated with extensive defects in the oral cavity and tongue and, therefore, the loss of necessary organism functions. Currently, there is no optimal autotransplant for tongue reconstruction after total or subtotal removal of the tongue and oral floor muscles; it appears to be one of the most significant challenges in modern reconstructive surgery.Materials and methods. The authors describe a case of successful repair of the oral floor and tongue after total glossectomy using a novel method developed in the Department of Microsurgery at the P. A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center, Ministry of Health of Russia. This method implies tongue reconstruction using a revascularized, reinnerved, chimeric, thoracodorsal flap with inclusion of a muscular portion from the serratus anterior muscle and a musculocutaneous portion from the latissimus dorsi muscle. We performed tongue reconstruction in a 62-year-old patient diagnosed with stage IVA (Т3N2bМ0) tongue cancer. Results. The novel method of surgical treatment of locally advanced tongue cancer with simultaneous repair of defects using a revascularized, reinnerved, chimeric flap with inclusion of the serratus anterior muscle and latissimus dorsi muscle allowed to remove the tumor, stabilize the laryngeal complex, restore the diaphragm of the oral floor, create an adequate volume of neotongue, obtain good functional and cosmetic results, and reduce the length of hospital stay. Conclusion. Novel method of surgical treatment of locally advanced tongue cancer facilitates health, employment, and social rehabilitation of patients with oropharyngeal cancer. This method can be considered as an alternative method of choice in the reconstruction of complex post-traumatic oropharyngeal defects

THE ROLE OF BRAF MUTATION STATUS IN SURGICAL TREATMENT OF WELL-DIFFERENTIATED THYROID CANCER

Background. Papillary thyroid carcinoma (PTC) accounts for 80 % of all well-differentiated thyroid cancers. Mutation of the BRAF gene (V600E) is one of the most common prognostic factors for PTC. Various studies showed different degree of correlation between BRAF (V600E) mutation and other prognostic factors.Materials and methods. 60 patients with PTC treated in P.A. Herzen Moscow Oncology Research Institute during 2014–2016 were included in this prospective study. Selection of patients was based on the results of fine-needle aspiration biopsy and polymerase chain reaction. Study participants were randomized into 2 groups: the first one included 45 patients harboring BRAF V600E mutation, the second one included 15 patients who lack this mutation. The following prognostic factors were evaluated in postoperative period: histological subtype of PTC, tumor invasion into the capsule of thyroid gland, multicentricity, presence of metastases in regional lymph nodes and distant metastases, TNM stage. Statistical data analysis was carried out using GraphPad Prism software.Results. Papillary thyroid cancer was diagnosed in 40 % of the patients, follicular thyroid cancer – in 60 % in both groups. Tumor invasion into the capsule of thyroid gland was identified in 88 and 40 % of the cases in the first and second group respectively; thyroid capsular invasion – in 26 and 10 %; multicentricity – in 20 and 10 %; microcarcinomas (0.3–1.0  cm) – in 57 and 60 %, metastasis to regional lymph nodes – in 40 and 30 %. 51 % of the patients in the first group were found to have pT1 thyroid cancer with tumor capsular invasion without spreading beyond. After surgical treatment 23 % of the patients from the first group had changes in tumor stage from cT1–2  to pT3 according to routine histological examination results. Distant metastases were observed in 5 % of the cases in the first group and in 10 % in the second group. We found a statistically significant association between BRAF (V600E) mutation and tumor invasion into the capsule of thyroid gland (p < 0.05). At the same time neither multicentricity nor metastases in regional lymph nodes were associated with BRAF-mutation (p > 0.05). Conclusions. BRAF mutation in patients with PTC is associated with tumor invasion into the capsule of thyroid gland; this should imply the use of more aggressive treatment strategy (surgery). Further studies are needed to clarify the existing data

ADJUVANT TREATMENT WITH BIPHOSPONATES IN COMPLEX THERAPY OF PAPILLARY THYROID CANCER BONE METASTASES

Distant metastasis of thyroid cancer are founded in 10% of all metastases. Bone metastases are founded in 23% of distant metastasis. Complications associated with metastatic skeletal involvement often lead to a deterioration in the overall condition and a decrease in the quality of life of patients. Surgical treatment, chemotherapy are less effective, provide a higher injury rate and toxicity. This is a reason of increasing of cost of treatment. Bisphosphonates are a class of drugs that prevent the loss of bone mass, which can prolong the time to releasing bone complications: bone fracture, spine column fracture with spinal medulla compression, which decrease the QoL. Surgical treatment and chemotherapy have worse outcomes, higher injury rate, toxicity and increase cost of treatment. Bisphosphonates decrease the level of pain syndrome. Bisphosphonates are used in treatment of oncological patients since 1990. First medication was Fosamax (Aledronat). Later more medications with better efficacy and more useful were synthesised. The last one was Zoledronic acid. Rezorba (zoledronic acid) was synthesised in 2006 in Russia. Rezorba has a same efficacy with other bisphosphonates, it was shown in clinical studies with groups of breast cancer and prostatic cancer. Clinical case of 67 y.o. male patient with diagnosis: Thyroid cancer IV c st pT1bN1bM1, right neck, paratraсheal, bone and lung metastasis. Complex treatment (surgery + radioiodine therapy + 5 courses of Rezorba) was presented. After 3 courses the level of pain was decreased from 3 to 1,5. After 5 courses the ECOQ score was decreased from 2 to 1 point. Inclusion of Resorba in complex treatment of patients with bone metastasis after thyroid cancer at all stages of treatment decreases the score of pain syndrome and bone tissue reparation