[Ippolit Vasilyevich Davydovsky -academician, educator, healthcare organizer]. / Ippolit Vasil'evich Davydovskii ­ akademik, pedagog, organizator zdravookhraneniya.

Ippolit Vasilyevich Davydovsky was born in 1887 in Danilov, Yaroslavl province, into the family of a clergyman. He received his primary education in a parochial church school. After I.V. Davydovsky's family moved to Yaroslavl, he continued his education in a men's gymnasium. Having successfully graduated from the gymnasium, I.V. Davydovsky in 1905 entered the medical faculty of Moscow State University, where he studied and was influenced by Acad. A.I. Abrikosov formed his first scientific interests. After graduating from the university in 1910, I.V. Davydovsky worked as a sanitary doctor and then as a zemstvo doctor. In 1912. I.V. Davydovsky received the title of Doctor of Medicine and a year later became a prozektor of the Yauza Hospital, which today bears his name. At this time, under the influence of Prof. M.N. Nikiforov, I.V. Davydovsky began to be interested in infectious pathology, which was later reflected in a number of his scientific works on typhus, paratyphus, dysentery and other infectious diseases.

[Relationship between PD-L1 expression and tumor stem cell marker CD44 as a promising basis for the development of new approaches to cancer targeted therapy]. / Svyaz' mezhdu ekspressiei PD-L1 i markerom opukholevykh stvolovykh kletok CD44 kak perspektivnaya osnova dlya razrabotki novykh podkhodov k targetnoi terapii novoobrazovanii.

Immunotherapy of malignant tumors is a rapidly developing area of oncology. PD-1 is a receptor expressed by activated T-lymphocytes. As a result of its interaction with the ligand (PD-L1 or PD-L2), the activity of T-lymphocytes is inhibited and their apoptosis occurs. Drugs that inhibit the interaction of PD-1 with ligands have an immunostimulatory effect and are effective in the treatment of many types of neoplasms: melanoma, lung cancer, bladder cancer, stomach cancer, various lymphomas, etc. However, response to this treatment is observed only in a narrow cohort of patients. To increase the effectiveness of immunotherapy, combined preparations and nanoparticles are being developed and created to enhance the effect of PD-L1 inhibitors, and containing hyaluronic acid as a ligand for the CD44 protein, which is expressed in many human tumors. However, the issue of co-expression of CD44 and PD-L1 remains poorly understood. This review is devoted to describing the features of co-expression and the mechanisms of interaction between CD44 and PD-L1. Promising directions for the development of new approaches to the immunotherapy of malignant tumors are presented.

Automated Assessment of the Area of Infiltration by CD8+ Cells in Gastric Carcinoma and Areas of Normal Mucosa as a Significant Prognostic Factor.

In 139 patients with verified gastric cancer, the infiltration of the postoperative material with CD8+ cells was analyzed. Automated morphometric analysis of immunostained slides was performed separately in different specimen sites (tumor center, invasive edge, and peritumoral mucosa). The mean area of infiltrating CD8+ cells in the tumor center and in the invasive edge was not predictive, while in the peritumoral mucosa it provided a new negative predictive factor (hazard ratio 2.10; confidence interval 0.87-4.92, Cox regression) reliably associated with the TNM stage (hazard ratio 1.91; confidence interval 0.91-4.61, Cox regression).

[Prognostic significance of PD-L1 expression as a potential predictor of survival in gastric cancer]. / Prognosticheskaya znachimost' ekspressii PD-L1 kak potentsial'nogo prediktora vyzhivaemosti pri rake zheludka.

BACKGROUND: Currently, PD-L1 expression in patients with tumors of various localizations is being actively studied. Studies on the expression of PD-L1 detected by clones SP142 and SP263 in gastric cancer (for the drugs atezolizumab and durvalumab, respectively) are rare in the literature. The prognostic role of PD-L1 expression in patients who were not treated with immune checkpoint inhibitors has also not been investigated. OBJECTIVE: To determine the expression level of PD-L1 (clones SP263 and SP142, Roche Ventana) in gastric cancer specimens and evaluate its effect on overall survival in patients who did not receive adjuvant therapy with immune checkpoint inhibitors. MATERIAL AND METHODS: The study included 131 patients with a verified diagnosis of gastric cancer. The material obtained from 127 patients was stained with antibodies to PD-L1 SP263, and from 126 patients - with antibodies to PD-L1 SP142. A multivariate Cox regression model with Wald's step-by-step exclusion algorithm was used to evaluate predictors of survival. RESULTS: The total five-year survival rate of patients in the PD-L1-negative tumor group was significantly lower than the total five-year survival rate of patients in the PD-L1-positive tumor group, which was 50.0% and 40.0% also for both clones (p=0.027). An increase in the expression of PD-L1 clone SP263, determined by both the CPS and TPS method, reduces the chances of death by 1.35 times (p=0.02) and 1.61 times (p=0.004), respectively. An increase in the expression of PD-L1 clone SP142, determined by the CPS method, reduces the chances of death by 1.54 times (p=0.005). CONCLUSION: The survival rate of patients in the group of PD-L1-positive tumors is significantly higher than in patients in the group of PD-L1-negative tumors. Elevated PD-L1 expression, as assessed by the SP263 and SP142 clones, is an important prognostic marker that predicts a higher chance of overall survival for patients, even though these patients are not receiving immune checkpoint inhibitors adjuvant therapy.

[Mucins expression in gastric cancer: connection of MUC status with clinical, morphological and prognostic characteristics of the tumor]. / Ekspressiya mutsinov v rake zheludka: svyaz' MUC-statusa s kliniko-morfologicheskimi i prognosticheskimi kharakteristikami opukholi.

OBJECTIVE: Clarification of the prognostic value and relationship of MUC-phenotypes of gastric cancer with clinical and morphological parameters. MATERIAL AND METHODS: Surgical material from 310 patients with a verified diagnosis of gastric cancer was studied. Samples were immunohistochemically stained with antibodies to MUC2, CD10, MUC5AC. The results were compared with clinical and morphological characteristics of gastric cancer and patient survival data. RESULTS: The MUC-null and MUC-mix groups significantly differ in the prevalence of subtotal/total tumors from the MUC-I group (p=0.022 and p=0.007, respectively), where there are significantly fewer such tumors. Tubular tumors were more common in the MUC-null group compared to the MUC-G (p=0.026) and MUC-mix (p=0.006) groups, and there were fewer cases with the presence of "signet-ring" cells in the MUC-null group (p=0.000). When studying the discohesive histological type, the literature data on smaller tumor sizes and a lower frequency of lymph node metastasis for MUC-G status were not confirmed, but a more frequent proximal localization of MUC-I tumors was found (p=0.003). No statistically significant differences in survival were found in the analysis of the total sample. Differences in survival were found only in discohesive cancers, where the best survival was recorded for the MUC-null group, and the worst for the MUC-mix group (p=0.022). MUC status is not an independent predictor of gastric cancer (HR=1.662, p=0.093). CONCLUSION: Between tumors with different MUC statuses, there were differences in localization and belonging to individual histological types. Significant differences in survival were found only for discohesive cancers with MUC-null and MUC-mix statuses. Separation of gastric cancers according to MUC status may have only limited predictive value in selected histological forms of cancer.

[PD-L1 expression in EBV-associated gastric carcinomas]. / Ekspressiya PD-L1 v EBV-assotsiirovannom rake zheludka.

OBJECTIVE: Assessment of the incidence of PD-L1 expression in EBV-associated gastric adenocarcinomas, as well as clarification of the clinical and morphological characteristics and median survival of patients with PD-L1-positive EBV-associated gastric cancer. MATERIAL AND METHODS: Samples of surgical material from 127 patients with stomach cancer were studied. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). Expression of PD-L1 was assessed immunohistochemically (PD-L1 SP263, PD-L1 SP142). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer and median survival of patients. RESULTS: The detection rate of PD-L1 SP263 and PD-L1 SP142 in EBV-associated gastric adenocarcinoma in our sample was 100% and 76.9% respectively, thus, PD-L1 expression (SP263, SP142) is significantly more frequently detected in EBV-associated gastric carcinomas. It was found that patients with positive expression of PD-L1 in EBV-associated gastric carcinomas are younger (mean age 56.3 years for SP263 and 55.6 years for SP142), belonging to male gender. In addition, this group is dominated by proximal localization of tumors, ulcerative form of growth, tubular histological type, intermediate subtype according to P. Lauren. These characteristics do not depend on the antibody clone: positive expression of SP142 and SP 263 was detected in the same patients with a few exceptions. The overall median survival of patients with positive PD-L1 status SP263 in EBV-associated gastric carcinomas was 35 months, for patients with positive PD-L1 status SP142 - 25 months. Median survival of SP142 PD-L1 positive patients is higher than overall median survival of PD-L1 negative patients in EBV-associated gastric carcinomas. It was found that PD-L1 status in EBV-associated gastric cancer is not a significant prognostic factor. CONCLUSION: A single PD-L1 status does not significantly affect the prognosis in patients with gastric cancer, including those in the group of EBV-associated carcinomas, and can only be considered in conjunction with 'classic' clinical and morphological characteristics, primarily with the stage of the tumor process, since they determine the prognostic properties of the tumor.

[Implantation materials in reconstructive surgery of the larynx and trachea]. / Implantatsionnye materialy v rekonstruktivnoi khirurgii gortani i trakhei.

The article presents a literature review, that analyzes the use of implantation materials in reconstructive plastic surgery of the larynx and trachea in patients with local and extended laryngeal-tracheal stenosis, including lumen obliteration. 48 literature sources were studied. The positive and negative aspects of biological and synthetic implant materials use have been determined. The choice of an implantation material that meets all the demands for the complete restoration of the respiratory tract determines the relevance of the problem raised.

[Pathomorphological aspects of urethral strictures of various etiologies].

INTRODUCTION: The study of the structure of strictures of various etiologies is an open and uncertain issue of modern urology. AIM: To evaluate the morphological and immunohistochemical structure of strictures of various etiologies. MATERIALS AND METHODS: The study involved postoperative tissue of a pathologically altered urethra of 110 patients aged 23 to 74 years who underwent treatment at the University Clinic of Urology, Russian National Research Medical University. N.I. Pirogova (2014-2018) with Ds: urethral stricture. Morphological study: Van-Gieson staining; hemotoxylin - eosin. Immunohistochemical study: mouse monoclonal antibodies to muscle and connective tissue markers (Smooth Muscle Actin, Vimentin, Calponin) and inflammation markers (CD45R, CD58, CD138, CD20, CD3) were used as primary antibodies in all reactions. RESULTS: According to the revealed morphological changes, the material was divided into three groups: group I (n=27) - active inflammation; group II (n=33) - the predominant development of connective tissue with low activity of inflammation; group III (n=50) - mixed (chronic mild inflammation, an even amount of connective tissue). In a morphological study of idiopathic urethral strictures, it was noted that the multicolumnar epithelium was replaced by a multi-layer flat epithelium with a weakly pronounced keratinization. Inflammatory changes were mild, including the submucosal connective tissue and the spongy body. Spongiofibrosis is accompanied by a significant reduction in the vascular bed of both venous sinuses and arteries. The same changes were observed in the inflammatory genesis of urethral strictures. In the study of strictures with traumatic etiology, a restructuring of the cylindrical epithelium was observed. In cases with severe inflammation in the mucosa, the changes were atrophic-hyperplastic in nature with reactive cell atypia. CONCLUSION: urethral Strictures in men have a specific etiological factor, but the pathogenesis of urethral lesions can be divided into: post-traumatic and post-inflammatory.