The Modern Concept of Using Radiation Therapy for Cancer of the Oral Cavity and the Oropharyngeal Area

In the world, there is a rise of cancer incidence, including cancer of the head and neck. The incidence cancer of the head and neck is 4.8 cases per 100 000 population. Oral and oropharyngeal cancers are the most frequently forms cancer of the head and neck – 4,8–27 % of all cancer with this location. Among the causes of oral and oropharyngeal cancer noted alcohol abuse, tobacco and infection with human papilloma virus (HPV-16). Mortality from oral and oropharyngeal cancer is on 8 rank among patients with all tumors. Now when deciding about treatment of oral and oropharyngeal cancer is applied a new classification АJCC8th, the main differences from the previous version are the inclusion of data on the depth of tumor invasion and the presence of extranodal growth of lymphogenic metastasis. The chemoradiotherapy to a total dose 60–74 Gy is the most common treatment used in oral and oropharyngeal cancer. When planning irradiation, both the tumor itself (or its residual component) and lymphogenic metastases or lymph nodes with a high risk of metastatic lesions are included in the target volume. The most commonly used chemotherapy drug is cisplatin. The duration of life of patients is significantly influenced by the stage of the tumor process. So 5-year relapse-free survival among patients with oral cancer is 91 % at T1–2, 83 % – at T3 and 12 % – at T4. During the first 5 years after completion of treatment, the probability of locoregional recurrence in patients with oropharyngeal cancer is much shorter in infected HPV-16 – 28.9 % and 54.9 %, respectively. The effective multimodal treatment of oral and oropharyngeal cancer can be only if the evaluation of the tumor process under the current classification, comply with the requirements of treatment standards and clinical guidelines as well as take into account the latest achievements of the relevant field of medical science.

Influence of the HLDF differentiation factor on the production of cytokines by bio-tissues of breast tissue in its non-malignant diseases and in invasive carcinoma of a non-specific type

We studied the effect of the HLDF differentiation factor on production of cytokines by biopsy samples of nonmalignant breast diseases (ND) and invasive breast carcinoma of no special type (IBC-NST), in the absence and presence of lymphogenic metastasis: IBC-NST patients werw subdivided into groups on the prognostic protocol of the 8th edition of the AJCC committee. Group IA consisted of patients with T1-T2 tumor sizes, and predominantly with positive expression of estrogen and progesterone receptors (ER+/PR+/HER2-); it also included one patient with the HER2+ (ER-/PR-/HER2+) molecular subtype. The IB group was mainly composed of patients with T2 tumor size, with the presence of lymphogenic metastasis (in 8 out of 10) patients and with positive expression of estrogen and progesterone receptors (ER+/PR+/HER2-) and it also included three patients with the HER2+ (ER-/PR-/HER2+) molecular subtype. Group IIA consisted of patients with T1-T2 tumor sizes, mainly with no metastases in the lymph nodes (in 11 out of 12 patients) and with a triple negative molecular subtype. Group IIB included patients with T2 tumor size, the presence of nodal metastasis and the expression of markers of ER-/PR-/HER2 - and ER-/PR-/HER2+. Group IIIA consisted of patients with tumor size T1-T3, with the presence of nodal metastasis and the expression of markers of ER-/PR+/HER2+ and ER-/PR-/HER2+. Group IIIC consisted of patients with T3 tumor size, lymphogenic metastasis, and expression of ER-/PR-/HER2-markers (triple negative molecular subtype). Due to a limited number of patients in the groups IIB, IIIA and IIIC, as well as due to more severe clinical and pathological stages, according to the prognostic Protocol of the 8th edition of the AJCC Committee, they were pooled into group III. Concentrations of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 were assayed in supernatants of biopsy specimens of breast tissue. Results have shown that with IBC-NST, a statistically significantly higher level of spontaneous production (SP) by biopsy specimens of IL-17, IL-18, IFN-γ and VEGF, and a lower level of SP IL-6 as compared with ND. Patients of all clinical and pathological groups showed a high VEGF spontaneous production as compared with ND, while statistically significant differences from patients with ND were not found in IL-17 spontaneous production in group IB patients, and IL-18 spontaneous production were absent in group IA. Only in patients with IA and IB, the IL-6 spontaneous production was lower as compared to ND, and the IL-8 spontaneous production was lower in the IA group. IFN-γ spontaneous production was higher in patients with IBC-NST group IIA as compared with ND. Under the influence of the HLDF differentiation factor, it was found that the parameters of IBC-NST patients were statistically significantly higher in the production of IL-1Ra, IL-17, IL-18 and VEGF, and statistically significantly lower in the production of IL-6 as compared to ND. HLDF had a higher impact on the content of IL-18 in IBC-NST patients than in ND. After HDLF sublimation IL-6 values were lower in patients of groups IA and IB, and HLDF-induced IL-17 production was higher only in patients of group IA. Statistically significant differences in the index of influence of HLDF (IVHLDF), representing ratio of the cytokine concentration in the supernatants of a biopsy specimen stimulated by HLDF to spontaneous cytokine production, were found between ND and IBC-NST in the case of on IFN-γ production, and also in the case of IL-4 production (between patients in the absence and presence of lymphogenic metastasis). IVHLDF for production of IL-6, IL-8 and TNF-α was lower in group IIA patients compared to group IA, and IVHLDF for production of GM-CSF and MCP-1 was lower in group IIA as compared to group III, in addition IVHLDF for MCP-1 products was lower in group IIA as compared to ND. The HLDF effect on the cytokine production by the tumor and its microenvironment was different in ND patients and IBC-NST patients. HDLF suppressed IFN-γ production in the pooled group of IBC-NST patients; HLDF mainly had a suppressive effect on the production of IL-6, IL-8, TNF-α, GM-CSF and MCP-1 in IBC-NST patients of group IIA.

CLINICAL AND MORPHOLOGICAL ASPECTS OF EARLY GASTRIC CANCER AND ASSESSMENT OF PROGNOSTIC FACTORS OF LYMPHOGENIC METASTASIS. (LITERATURE REVIEW)

To determine the strategy of treatment of EGC in the world today indications for endoscopic resection, proposed by JGCA, is being used. These indications are presented by a number of morphological factors of the EGC, which are correlate with a low level of lymphogenic metastasis. Not all of the medical centers think these indications are safe. There are publications that question the value of these morphological factors, as well as the heterogeneity of the assessment. Also, in addition to the generally recognized indications for ER JGCA, the researchers proposed other algorithms for the selection of EGS patients with low risk of metastasis to perform ER. These methods were developed using regional standards for different ethnic groups and based on different prognostic parameters. In our review, publications in well-known medical journals in English found through computer search were investigated to study the ways of measuring morphological factors and the safety of jgca readings to ER. The search included such terms as “early gastric cancer”, “prognostic factors”,” lymphogenic metastasis”,” endoscopic resection of the PANCREAS “and “absolute and extended indications for endoscopic resection”. The review includs 60 original studies and meta-analyses. In the original studies, the correlation of demographic and morphological characteristics of the tumor and metastatic process were studied, the variants and methods of evaluation of morphological factors were investigated. The meta-analyses researched the correlation between ER and BREAST surgery, compared the level of safety of absolute and relative criteria of endoscopic resection.

THE FIRST EXPERIENCE OF USING LAPAROSCOPIC GAMMA PROBE FOR INTRAOPERATIVE VISUALIZATION OF SENTINEL LYMPH NODES IN GYNECOLOGICAL CANCER

Visualization of sentinel lymph nodes (SLN) is now widely accepted for lymph node (LN) detection using a radioactive lymphotropic trace. Preoperative lymphoscintigraphy with intraoperative lymphatic mapping under gamma detecting probe guidance proved to be an easy and reliable method for SLN detection.Material and methods.In this article we present our experience in using laparoscopic gamma-probe for intraoperative visualization of sentinel lymph nodes in gynecological cancer.Results.Intraoperative visualization of sentinel lymph nodes in young cervical cancer patients and in patients with stage I endometrial cancer allowed us to perform radical surgery with personalization of the extent of lymph node dissection, especially for patients with low and intermediate risks of lymphogenic metastasis.

A LINK BETWEEN AUTOPHAGY REGULATORY PROTEINS M-TOR AND BECLIN-1 AND PARAMETERS OF LYMPHOGENIC METASTASIS IN COLORECTAL CANCER

Currently the impact of autophagy on carcinogenesis remains understudied. On the one hand, autophagy acts as a tumor suppressor, as it activates degradation of oncoproteins, toxic proteins, and damaged cell organelles, that may be aggressive and lead to DNA damage. On the other hand, autophagy may promote tumor cell survival under hypoxia and in the presence of reactive oxygen species, which occurs primarily due to blocking of apoptosis mechanisms, raising the chances for maintaining tumor clone dynamics. Autophagy regulation is a complicated and multi-stage process. The main regulator here is a signaling pathway that activates serine/threonine protein kinase m-TOR (the mammalian target of rapamycin). Data on the impact of autophagic proteins ATG5, LC3A, LC3B, and Beclin-1 on malignant cell survival as well as on tumor growth and progression have been reported in literature. However, studies aimed at seeking possible relationships between autophagy and pathogenetic mechanisms of carcinogenesis are of great interest.Theaimof the study is to investigate a relationship between the expression parameters of autophagy regulatory proteins m-TOR and Beclin-1 and the features of lymphogenic metastasis in colorectal cancer.Materials and methods. The study included 105 patients with T1-4N0-3M0 colorectal cancer treated in the Thoracic and Abdominal Department of Cancer Research Institute of Tomsk Research Medical Center from 2012 to 2015. The average age of patients was 59.7±4.3 years. Morphological verification of the diagnosis was performed on the biopsy samples of primary tumor tissue. Staging of colorectal cancer was determined according to the TNM classification of malignant tumors (2002).Results.Analysis of the frequency of lymphogenic metastasis depending on the presence or absence of m-Tor and Beclin-1 expression in tumor cell cytoplasm revealed a statistically significant link between these variables.Conclusion.The obtained findings clearly exhibit that deceleration or loss of autophagic activity in the tumor is accompanied by implementation of lymphogenic dissemination, which is a predictor of an unfavorable outcome of the disease.

RELATIONS OF PROTEASOMAL SYSTEM WITH TUMOR STAGE IN LUMINAL BREAST CANCER

The aim of this study was to investigate characteristics of the proteasomal system in luminal breast cancer. There were included 124 patients with primary luminal breast cancer in stage Т13N0-2M0 who had not received neoadjuvant treatment. The process of lymphogenous metastasis was associated with a significant change in caspase-like activity (CL) and subunit composition of proteasomes. CL activity of proteasomes was increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), while it was decreased in the luminal B subtype of cancer. It was accompanied by an increase in the composition of the proteasomal total pool subunits, regulatory and immune subunits. Decrease in CL activity of proteasomes can be poor prognostic sign which is associated with the lymphogenous invasion of the tumor process in luminal B breast cancer.