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Background. Currently, there is a steady trend towards an increase in the incidence of both synchronous and metachronous multiple primary malignant tumors (MPMT). However, metachronous polyneoplasia of the pancreatobiliary tract is relatively rare, and there have been very few reports on successful treatment of this malignancy. Case presentation. In September 2014, the patient K. was diagnosed with adenocarcinoma of the ampulla of Vater (T2N0M0, stage Ib) and underwent gastropancreatoduodenal resection with the creation of pancreatic-gastric anastomosis at the Abdominal Department of Cancer Research Institute of Tomsk National Research Medical Center. There were no complications in the postoperative period. At a 6.5-year followup, no evidence of disease progression was found. In April 2021, a follow-up examination conducted at the Cancer Research Institute revealed a large lesion on the distal part of the pancreatic stump with no clinically significant manifestations. Diagnosis of MPMT was confirmed by transgastric endoscopic ultrasound-guided biopsy. Histological and immunohistochemical examinations revealed undifferentiated ductal carcinoma of the pancreas. Considering the metachronous tumor localization, pancreatic stump extirpation with resection of the posterior wall of the stomach and splenectomy was performed. No complications occurred in the postoperative period. The patient received replacement therapy for exocrine pancreatic insufficiency and individual correction of carbohydrate metabolism. At a 15-month follow-up, liver metastases were detected, and palliative chemotherapy was administered. The patient died 6 months later due to disease progression. The survival time was 99 months after the first surgery and 21 months after the second surgery. Conclusion. We report a rare case of metachronous cancers of the ampulla of Vater and pancreatic stump developed with an interval of 6.5 years. The patient underwent successful curative resections consecutively. The overall survival time from the date of diagnosis was 99 months.

Background. Overexpression of Her2neu occurs in 15–20% of patients with gastric cancer and correlates with an unfavorable prognosis. Case report. We report a case of pathological complete regression of resectable gastric cancer with Her2/neu overexpression. The patient received combined modality treatment including 8 cycles of neoadjuvant chemotherapy with mFLOT + trastuzumab followed by R0 resection. The addition of targeted therapy did not have a negative impact on the perioperative period. Histolohical examination of the surgical specimen revealed pathological complete response (Mandart TGR1). Currently, the patient has been followed-up for 27 months without signs of disease relapse. Conclusion. Total neoadjuvant chemotherapy with mFLОТ+ trastuzumab for operable gastric cancer with Her2/neu overexpression allows us to hope for improved long-term treatment outcomes.

Neutrophilic granulocytes have a wide spectrum of functional activity. In recent years, the functional significance of neutrophils in the development and course of malignant neoplasms has been discussed. It has been shown that neutrophilic granulocytes can play pro- or antitumor activity. The aim of the study was to assess the structural and functional features of neutrophils in patients with varying degrees of prevalence of cancer of the larynx and laryngopharynx. Forty-one patients (aged 35-67) with newly diagnosed cancer of the larynx and laryngopharynx were examined and divided into subgroups according to the TNM classification: the first subgroup (14 patients) with a localized tumor process consisted; and the second subgroup (27 patients) with a widespread tumor process. The relative and absolute number of neutrophils was assessed, and the neutrophil-lymphocyte ratio (NLR) was determined. The content of neutrophils with varying degrees of nuclear segmentation in the blood was calculated, the activity of myeloperoxidase, cationic proteins, alkaline phosphatase, and the degree of neutrophil activation in the NBT test was determined cytochemically. Concentration of interleukin-8 was determined using ELISA. In patients with cancer of the larynx and laryngopharynx the number of neutrophils (p = 0.045) and NLR (p = 0.033), as well as serum concentration of interleukin 8 (p = 0.011), increased compared to healthy individuals. The proportion of cells with hypersegmented nuclei in the neutrophil population (p < 0.001) and cytotoxic potential increased with the spread of tumor process. A direct correlation (r = 0.42, p = 0.03) was found between the T index, which reflects the volume of the tumor, and the content of hypersegmented neutrophils. It can be argued that such a simple and accessible laboratory parameter as the degree of segmentation of the nuclei of neutrophilic granulocytes can be used as one of the criteria to assess and predict the course of the tumor process.

The purpose of the study was to assess the short-term effcacy and tolerability of neoadjuvant chemotherapy (NAC) in colorectal cancer (CRC) patients with isolated liver metastasis.Material and Methods. Since 2020, a pilot study including 23 CRC patients with liver metastasis has been conducted at the Abdominal Cancer Department of the Cancer Research Institute (Tomsk, Russia). The combined treatment modality included 3 cycles of NAC according to FOLFOXIRI + cetuximab (20 patients with wtKRAS) and FOLFOXIRI + bevacizumab (3 patients with mtKRAS) regimens followed by simultaneous laparoscopic colorectal resection and open liver resection.Results. For liver metastases, the objective response rate reached 100 % (complete response: 8.7 %, partial response: 91.3 %). For the primary tumor, the objective response rate was 100 % (partial response). The overall NAC toxicity rate was 53.6 %. The major I–II grade toxicities included nausea/vomiting (27.5 %), polyneuropathy (10.1 %), skin reaction (10.1 %), hepatotoxicity (5.8 %), and corresponded to I–II grade. R0 resection was performed in all patients. Postoperative complications were observed in 19 (82.6 %) patients; of them 18 (78.3 %) had a febrile temperature (grade 1, according to the Clavien–Dindo classifcation) due to the use of bipolar coagulation during liver surgery, and 1 (4.4 %) patient developed a biliary fstula (3 A/B grade according to Clavien–Dindo). No postoperative death occurred. For liver metastasis, pathological complete response rate was 4.4 % (TRG1 according to Mandard); for the primary tumor, in most cases was TRG 3 – 87 %.Conclusion. Combined treatment modality, including NAC with FOLFOXIRI regimen and targeted therapy for CRC with liver metastases, is well tolerated, has a signifcant damaging effect on the tumor, and does not affect the course of the postoperative period. Further studies are required to assess the long-term treatment outcomes.

Introduction. To date, one of the reasons for the ineffectiveness of chemotherapy in various malignant neoplasms, including lung cancer, is the formation of the multidrug resistance (MDR) phenotype in tumor cells, which is caused by the expression of ABC transporter genes.Aim. The aim of this work was to assess the expression of ABC-transporter genes during chemotherapy and to analyze the relationship with the effectiveness of chemotherapy and prognosis of the disease.Materials and methods. We used biopsy and surgical material from 91 patients with stage IIB–IIIA non-small cell lung cancer (NSCLC). The treatment regimen included: 2 courses of neoadjuvant chemotherapy (NAC), surgery and 3 courses of adjuvant chemotherapy (ACT) with platinum doublets. RNA was isolated from the samples, followed by quantitative PCR to assess the expression of genes ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2.Results and discussion. It was shown that the level of expression of the studied genes was not associated with the effect of NAC in patients with lung cancer, except for the ABCC5 gene, which showed a relationship at the level of a pronounced trend (p = 0.07). It was also shown that in the group of patients with an objective response to chemotherapy, the frequency of decreased expression of the ABCC1 (p = 0.01) and ABCC5 (p = 0.004) genes was statistically significantly higher than in the group of patients with stabilization. Further, using the Kaplan – Meier method, it was found that a decrease in expression is associated with high rates of metastatic-free survival (MFS). The highest rates of 5-year MFS (more than 85 %) are observed in patients with a decrease in the expression of the ABCB1 and ABCG2 genes, log-rank test p = 0.0007 and p = 0.002, respectively.Conclusion. Thus, it has been shown that changes in the expression of ABC transporter genes are associated with the effectiveness of chemotherapy and the prognosis of the disease. The data obtained can be used as a basis for the detection of potential drug targets.

Introduction. In most patients with colorectal cancer (CRC), the tumor develops against the background of metabolically healthy obesity or metabolic syndrome (more than 60 % of patients), the key pathogenetic moment of which is developing hyperinsulinemia. Metabolic changes are also characteristic of patients with colon polyps (CP), which are currently considered as the most significant precancerous diseases. It has been shown that fractions of small extracellular vesicles (EVs) of adipocyte origin are specifically enriched in extracellular matrix proteins, including matrix metalloproteinases (MMPs), chaperones, and some metabolic enzymes involved in the synthesis of lipids and carbohydrates. This was the reason for choosing exosomal markers in our study. Comparison of protein expression on CD9- and FABP-4 positive vesicles will be useful to explain some clinical issues, such as the effectiveness of thermoradiotherapy or radiotherapy in obese CRC patients; for a more substantiated search for vesicular prognostic markers in obese cancer patients. However, taking into account the lack of data in the literature on the level of MMPs and HSPs expression in the composition of the total pool of EVs and in the composition of FABP4-positive EVs in patients with PTC and CRC patients, the aim of the work was formulated.Aim. Study of the level of MMPs and heat shock proteins (HSPs) on CD9- and FABP4-positive EVs in patients with CP and CRC in relation to metabolic status.Materials and methods. The study included 12 patients with CRC (T2-4N0-2M0; mean age 59.6 ± 1.6 years) who were treated at the Department of Abdominal Oncology of the Cancer Research Institute of the Tomsk National Research Medical Center from 2019 to 2021. The comparison group included 10 patients with CP. The level of proteins on the surface of CD9- and FABP4-positive EVs was studied using flow cytometry.Results. MMP9-positive EVs were detected more often in CRC patients than in CP patients, however, MMP9+MMP2+TIMP-positive EVs were significantly more frequently detected in CP patients. Among the studied heat shock proteins, HSP60 was most often expressed on the surface of EVs, and HSP60-positive EVs were detected on the surface of CD9-positive exosomes in patients with PTC much more often than in CRC. In patients with CRC, compared with patients with СP, among FABP4-positive EVs, the proportion of triple-positive EVs and EVs with the MMP9+MMP2-TIMP1+ phenotype significantly increases, which in general may indicate overexpression of MMP9 and TIMP1 by adipocytes or marcrophages of adipose tissue in patients with CRC. Correlation analysis revealed multiple correlations of individual phenotypes of CD9-positive EVs in patients with CRC with body mass index and serum high density lipoprotein cholesterol levels, while the phenotypes of FABP4-positive EVs were associated mainly with triglyceride levels.Conclusions. The phenotypes of CD9-positive and FABP4-positive circulating EVs are promising as predictors for clarifying cancer risk in patients with colon polyps, as well as in terms of explaining the effectiveness of the treatment of CRC patients with obesity or metabolic syndrome.

Background. Currently, perioperative chemotherapy is the standard treatment option for resectable gastric cancer (GC ) at stages higher than T1. Preoperative chemotherapy was shown do not adversely affect the course of the postoperative period in gastric cancer patients. However, approximately 60 % of radically operated patients complete adjuvant chemotherapy. In this regard, the problem arises of postponing all courses of chemotherapy for operable gastric cancer to the preoperative period.The purpose of the study was to analyze short-term efficacy and toxicity of total neoadjuvant chemotherapy with FLOT regimen in patients with resectable gastric cancer.Material and Methods. Since 2020, the Research Cancer Institute of Tomsk National Research Medical Center has been conducting a pilot study, which included 25 patients with resectable gastric cancer (T2–4N0–2M0) who received 8 cycles of neoadjuvant chemotherapy with FLOT regimen followed by radical surgery (gastrectomy or distal subtotal resection of the stomach).Results. Preoperative chemotherapy was completed in 25 (100 %) patients. Side effects that occurred during chemotherapy did not require cancellation or interruption of treatment and reduction in the initial dose of drugs. The most common adverse events were emetogenic reactions (92 %), peripheral neuropathy (60 %), and neutropenia (48 %). All patients had no greater than grade II toxicity, which was reversed with standard maintenance therapy. Radical surgeries were performed 6 weeks after completion of chemotherapy cycle 8. There were no significant postoperative complications (grade III or higher according to the Clavien–Dindo scale) and deaths. The histological examination revealed pathological response of TG R2–3 grade in 21 (84%) patients. Downstaging in both T and N categories was found in 13 (52%) patients.Conclusion. Eight cycles of total neoadjuvant chemotherapy for resectable gastric cancer demonstrates high efficacy, moderate toxicity, and do not adversely affect the course of the perioperative period.

The purpose of the study: to analyze short-term efficacy and tolerability of preoperative chemotherapy in patients with upper ampullary rectal carcinoma. Material and methods. A prospective study conducted at the cancer research institute (tomsk, russia) between 2018 and 2020 included 47 patients with operable cancer of the upper ampullary part of the rectum with mrt3n0m0 (mesorectal fascia involvement (crm+) or low-grade cancer), mrt4аn0m0 and mrt3–4аn1m0. All patients were divided into two groups. Group i comprised 22 patients, who received 3 cycles of chemotherapy with folfox-4 followed by surgery. Group ii consisted of 25 patients, who underwent surgery alone. All patients underwent arterior resection of the rectum. Results. Group i patients completed all three cycles of preoperative chemotherapy. Downstaging after chemotherapy was observed in 16 (72.7 %) patients. No severe side effects of chemotherapy were found. The frequency of radical surgeries (r0) was 100 %. No significant differences in the rate of postoperative complications between the treatment groups were observed (18.2 % and 16 %, respectively, p>0.05). There were no cases of postoperative mortality. Conclusion. Compared with surgery alone, preoperative chemotherapy followed by surgery demonstrates a high short-term efficacy, does not adversely affect the course of the perioperative period.

Background. The calpain proteolytic system plays an important role in the development of cancer. Detection of early cancer in the upper respiratory tract is often challenging, as symptoms are largely non-specific, and most cases are diagnosed at an advanced stage.Aim. To identify candidate markers of transition from premalignant lesions to invasive carcinoma, we studied mRNA expression levels of CAPN1 and CAPN2 and the total activity of calpains in the tumor tissues of patients with head and neck squamous cell carcinoma (HNSCC) and in the epithelial dysplasia-affected tissues of patients with chronic diseases of the upper respiratory tract.Materials and methods. The study included 32 patients with HNSCC (Т1-3N0-1М0) and 12 patients with chronic diseases of the upper respiratory system associated with epithelial dysplasia. The expression levels of CAPN1 and CAPN2 were assessed using real-time polymerase chain reaction (PCR). The calpain activity was determined by hydrolysis of the fluorogenic Suc-LLVY-AMC oligopeptide.Results. The mRNA expression levels of CAPN1 and CAPN2 were respectively 3 and 4 times higher in the tumor tissue of patients with HNSCC than in the tissue of patients with endothelial dysplasia in the upper respiratory tract. The level of calpain activity was 4.4 times higher in patients with HNSCC than in patients with epithelial dysplasia of different severity.Conclusion. The elevated mRNA expression levels of CAPN1 and CAPN2 and their activity in the tumor tissues of patients with HNSCC compared to patients with chronic respiratory diseases associated with epithelial dysplasia are likely to characterize a high potential for transition from precancerous lesion to cancer. To clarify the role of calpains in the carcinogenesis of HNSCC, further studies of intact tissues using animal models are required.

Introduction. Identification of persons with a high oncological risk to squamous cell carcinoma of the head and neck region is an urgent problem for the early diagnosis of this disease. The activity of circulating proteasomes can be a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the upper respiratory and gastrointestinal tracts. The aim of the study is to investigate the chymotrypsin-like and caspase-like activities of circulating serum proteasomes depending on the localization of precancerous and neoplastic diseases of the larynx and oral cavity. Material and Methods. The study population consisted of 35 patients with histologically verified HNSCC (T1–3N0–3M0), 15 patients with chronic hyperplastic laryngitis (CHL) and oral leukoplakia, and 10 healthy volunteers who did not have chronic upper respiratory tract diseases in the acute stage. The median age of the patients was 53 ± 5.3 years. Results. An increase in the studied proteasome activities was found in the blood serum of patients with malignant tumors as compared with patients with chronic hyperplastic diseases associated with precancerous changes, as well as in the larynx and oral cavity cancers groups as compared with healthy donors. At the same time, depending on the localization of the pathological process, it was shown that only the chymotrypsin-like activity of the circulating pool of proteasomes significantly differs both in the groups of oral cancer leukoplakia, and in the groups of laryngeal cancer chronic hyperplastic laryngitis with dysplastic epithelial lesions. In addition, differences were found between chymotrypsin-like and caspase-like activities of circulating serum proteasomes in patients with chronic hyperplastic laryngitis with oral dysplasia and leukoplakia. Conclusion. The results obtained indicate that the determination of the CTp activity of the circulating pool of proteasomes can be used as a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the larynx and oral cavity.

To date, the role of human papillomavirus (HpV) in the development of lung cancer is still under investigation. The available published data do not provide evidence of the involvement of HpV in lung cancer pathogenesis. In Russia, there are no reports regarding the studies of viral contribution to lung carcinogenesis.The aim of the present study was to examine the presence of high-risk HpV infection in patients with non-small cell lung cancer (NSCLC).Material and Methods. The study included 30 patients with histologically verified stage IIBIIIA NSCLC. Normal and tumor lung tissue samples as well as whole blood samples from each patient were used. dNA was isolated from tissue samples using the QIAamp dNA mini Kit (Qiagen, Germany). Amplisens® reagent kits (Moscow, Russia) were used for dNA isolation and genotyping.Results. The presence of HpV dNA was detected in 3 (10.0 %) patients. HpV dNA was not detected in 27 (90.0 %) patients. HpV-16 genotype was observed in 2 HpV-positive patients, and HpV-33 was observed in 1 patient. A clinically insignificant viral load was found in almost all HpV-positive samples. The assessment of the virus integration in HpV16-positive lung cancer patients revealed mixed and integrated forms of the virus in the tumor tissue of these patients. The 5-year metastasis-free survival rate in all HpV-positive patients was 100 %.Conclusion. Our data showed HpV dNA prevalence rate of 10 % among NSCLC patients in the Russian population. The presence/absence of a viral component for lung cancer patients is a clinically significant parameter.

High aggressiveness of laryngeal and hypopharyngeal squamous cell carcinomas dictates the necessity of studying the molecular mechanisms of metastasis. Cancer metastasis is associated with remodeling of the cytoskeleton, which is carried out by actin-binding proteins (ABPs). Currently, there is insufficient data on the feasibility of determining the level of circulating ASBs in lymphogenous metastasis of laryngeal cancer (LC). Material and Methods. Blood serum analysis was carried out in 42 LC patients and 15 healthy volunteers using ELISA kits on a microplate ELISA reader Multiskan FC 100 (ThermoFisher Scientific). Among ASBs, cofilin1 (CFL1), fascin1 (FSCN1), ezrin (EZR), profilin1 (PFN1), adenylyl cyclase associated protein 1 (CAP1) were studied. Statistical processing of the results was performed using the Statistica 6.0 software package. Results. It was shown that the serum level of CAP1 was significantly higher in patients with LC compared with the group of healthy volunteers (p=0.00). As the size of the primary tumor increased, the levels of FSCN1, CAP1 and PFN1 significantly increased. The level of FSCN1 was 10 times higher and the level of CAP1 was 40% higher in LC patients with metastases than in LC patients without metastases. Thus, among the studied ASBs, FSCN1, CAP1, and PFN1 play an important role in the pathogenesis of LC. Conclusion. The results of the serum level of ASB in LC were obtained for the first time, and they determine the fundamental basis for the development of new methods for predicting the development of metastases.

Previous studies of the morphological features of head and neck squamous cell carcinomas revealed a significant association of the presence of discrete tumor cells and a low level of inflammatory infiltrate with lymphogenous metastasis. The aim of the study was to evaluate the quantity of tumor cells undergoing epithelial-mesenchymal transition (EMt) in tumor cell structures of different degrees of differentiation and to assess the prognostic model of lymphogenous metastasis based on the studied parameters. Material and methods. the main clinical tumor characteristics and morphological patterns of the tumor were assessed in 92 patients. the expressions of snail and Vimentin proteins were studied in 16 patients using confocal microscopy. Results. the expression of the EMt marker in cell structures of different degrees of differentiation was evaluated; the maximum number of snail- and Vimentin-positive cells (20 % each) was observed in discrete tumor cells. No difference in the proportion of cells undergoing epithelial-mesenchymal transition between patients with and without lymphogenous metastasis was found. thus, the prognostic model of lymphogenous metastasis included: the presence of single tumor cells and low level of inflammation. the sensitivity of the model was 54.5 %, and specificity was 89 %.

The objective is to evaluate the contents of matrix metalloproteinases (MMP) MMP9, MMP2, as well as their inducer EMMPRIN in circulating exosomes of patients with colorectal cancer in relation with clinical and morphological parameters, as well as with the presence of metabolic syndrome to search for promising exosomal markers associated with invasion, metastasis and metabolic disorders.Materials and methods. The study included 40 patients with colorectal cancer (T2–4N0–2M0–1) and 10 control patients. Exosomes of blood plasma were isolated by ultrafiltration with ultracentrifugation. The level of MMP9, MMP2 and their inducer EMMPRIN in exosomes was evaluated by flow cytometry.Results and conclusion. The level of MMP9‑positive exosomes was significantly higher in patients with colorectal cancer compared with patients with colorectal polyps. The proportion of MMP9‑negative and triple positive MMP9 + / MMP2+ / EMMPRIN+ exosomes, on the contrary, was higher in patients with polyps compared with patients with colorectal cancer. Mixed subpopulation of MMP9+ / MMP2– / EMMPRIN-exosomes prevailed both in patients with colorectal cancer and in control patients. There were no significant differences in the subpopulations of MMP and EMMPRIN in the exosomes of colorectal cancer patients depending on the age, stage, grade and localization. Gender differences in the occurrence of a triple-positive exosome subpopulation in colorectal cancer patients have been revealed. No relationship was found between the expression of MMP and EMMPRIN in exosomes and the presence of the metabolic syndrome, anthropometric parameters, the level of total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol. However, the relationships between MMP9+ / MMP2– / EMMPRIN–, MMP9+ / MMP2– / EMMPRIN– and the level of triglycerides and glucose in blood serum were revealed. Further studies are needed to study the characteristics of exosomes associated with metabolic disorders and the possibility of their use as diagnostic, prognostic, or predictor biomarkers.

The purpose of the study was to provide current data about various methods of treatment of early and locally advanced esophageal cancer.Material and Methods. A search was made on available literature sources published in the Pubmed, Medline, Elibrary, Cochrane Library, CyberLeninka, Global Health and other databases. 123 articles published from 2001 to 2018 were found and analyzed to write this review.Results. Esophageal cancer is the 7-th most common cancer worldwide. Esophageal cancer has a favorable prognosis only in patients with early stage cancer. The use of endoscopic technology provides a minimally invasive approach to the treatment of esophageal cancer and significantly increases survival of patients. Surgical resection remains the mainstay of treatment for esophageal cancer. For patients with locally advanced esophageal cancer, a multimodal approach is required, including a rational combination of radical surgery with chemo and/or radiation therapy. In many countries, preoperative chemotherapy has entered the standard of treatment for II–III stages of esophagus cancer. However, the development of novel approaches to the treatment of esophageal cancer is of great importance. For advanced cancer patients, palliative chemo- or chemoradiotherapy remains the main treatment modality.Conclusion. The choice of the treatment option for esophageal cancer remains a challenging clinical problem and depends on the particular type of cancer, tumor stage, functional status of patients.

Surgical treatment is leading in the treatment of malignant tumors of the salivary glands. The complexity of the anatomical areas, the severity of the tumor process, the close location of the facial nerve branches lead to frequent complications in the postoperative period. The technique of elimination of paresis of mimic muscles with the use of a complex of therapeutic measures, including a course of physiotherapy with the appointment of a magnetolaser and SCENAR therapy developed at the Cancer Research Institute, Tomsk National Research Medical Center of the RAS and the prospect of its use in this pathology. The clinical case of application of this material is described.

The objective response rate to neoadjuvant chemotherapy (NAC) in patients with non-small cell lung cancer (NSCLC) is approximately 16 %. Therefore, the search for new predictive factors and markers that could precisely predict the NAC response and be relevant to the choice of the adequate treatment policy is of utmost importance. the purpose of the study was to analyze the relationship between the expression levels of chemosensitivity genes and NAC response in patients with non-small cell lung cancer. material and methods. The study included 30 patients with stage IIAIIIB NSCLC. Total RNA was isolated from normal and tumor lung tissue samples prior to NAC. The expression level of chemosensitivity genes, such as BRCA1, RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, and GSTP1 was evaluated by real-time reverse transcriptase quantitative PCR (RT-qPCR). results. A significant difference in the expression levels of the studied genes between patients with different NAC response was found. The objective response to therapy was observed in 67 % (10/15) of patients having no ERCC1 expression compared to those with ERCC1 expression (p

Objective: to analyze the association between inflammatory cells with morphological heterogeneity and lymphogenous metastasis of head and neck squamous cell carcinoma.Material and Methods. Five types of tumor structures, the level of inflammatory infiltration and the counts of CD4+ and CD8+ t-lymphocytes, B-lymphocytes and macrophages in the stromal infiltrate and Langerhans cells in tumor structures were assessed in 44 patients.Results. The presence of Langerhans cells in type 1 structures was correlated with the presence of CD3+ and CD4+ t-cells in the inflammatory infiltrate. There was a decrease in the inflammatory reaction and the number of CD3+ T cells in patients with metastatic lymph nodes compared with patients with intact lymph nodes. In patients with lymph node metastasis, the proportion of CD4+ and / or CD8+ and / or CD20+ lymphocytes in the infiltrate was higher in cases with well-differentiated tumor than in cases with poorly-differentiated tumor.Conclusion. The results obtained showed the decrease in the level of inflammatory response, including t-cell response, as well as the relationship between the presence of Langerhans cells and stromal inflammatory response in patients with lymph node metastasis.

Background. A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC).The aim: to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia.Material and methods. As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and DNA samples) and data of the population-based registry of GC (2012) were compared. Gastric cancer patients were matched by age and sex to HAPIEE population controls. A total of 156 serum samples (GC – 52, control – 104) and 146 DNA samples (GC – 50, control – 96) were available for prospective analysis. DNA samples from 80 gastric cancer patients (45 men and 35 women, mean age 61.0 ± 13.4 years) and from 87 age-and sex-matched controls were analyzed. DNA samples from venous blood were genotyped according to standard methods. Serum samples were tested using diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori.Results. No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were found. A decreased frequency of the Pro allele in female gastric cancer patients compared with controls indicated that the Pro allele is protective against the development of gastric cancer, but this effect was not observed in male patients. No associations of TP53 genotypes with the risk of diffuse or intestinal gastric cancer, as well as with the age and sex of patients were found. A high frequency of genotypes with the Pro allele in patients with stage III–IV gastric cancer indicated the relationship between Arg/Pro TR53 and tumor progression, in particular, the contribution of the minor Pro allele to the unfavorable prognosis. A prospective study showed high risk of reducing the level of pepsinogen for assessing predisposition to gastric cancer.Conclusion. Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.

Introduction. The choice of adequate treatment for cancer patients and their survival rates signifcantly depend on the precise detection of the primary tumor and the assessment of the extent of cancer involvement. Despite advances in the treatment of laryngeal/hypopharyngeal cancer, many aspects of this problem are still unresolved. The purpose of the study. Diagnostic capabilities of nuclear medicine imaging in the detection and assessment of the spread of laryngeal/hypopharyngeal cancer were studied. Material and methods. The study included 40 patients with histologically verifed laryngeal/ hypopharyngeal cancer, 10 patients with tumor recurrence after completion of therapy and 20 patients with benign laryngeal lesions. Single photon emission computed tomography (SPECT) was performed 20 minutes after the injection of 99mTc-methoxy-isobutyl-isonitrile (MIBI). Sentinel lymph nodes (SLNs) were detected in 26 patients after submucosal injections of 99mTc-Tehneft or 99mTc-Alotech around the tumor. In 18 hours after the injection of 99mTc-Tehneft and 99mTc-Alotech, SPECT was performed. In 24 hours after the injection of 99mTc-Tehneft and 99mTc-Alotech, intraoperative SLN detection was performed using Gamma Finder II. Results. SPECT with 99mTc-MIBI revealed laryngeal and hypopharyngeal tumors in 38 of the 40 patients. The 99mTc-MIBI uptake in metastatic lymph nodes was visualized in 2 (17 %) of the 12 patients. 28 SLNs were detected by SPECT and 31 SLNs were identifed using the intraoperative gamma probe. The percentage of lymphotropic radiopharmaceuticals in the SLN was 5–10 % of the radioactivity in the injection site by SPECT and 12–33 % by intraoperative gamma probe detection. Conclusion. SPECT with 99mTc-MIBI is an effective tool for the diagnosis of laryngeal/hypopharyngeal cancer. The sensitivity, specifcity and accuracy of this technique were 95, 80 and 92 %, respectively. The use of 99mTc-Tehnefte and 99mTc-Alotech for the detection of SLN in laryngeal/hypopharyngeal cancer patients was characterized by high effcacy, while intraoperative detection was more sensitive, being 80 and 100 %, respectively.

To predict the development and clinical course of squamous cell head and neck carcinoma (SCHNC), we studied the level of protein phosphatase 1B (РРМ1В) using the proteomic analysis. Verification of the results of proteomic analysis by ELISA showed that the level of РРМ1В in blood serum of patients with SCHNC depended on the disease stage. The level of РРМ1В in the blood serum of patients with stage T1N0M0 cancer was higher than that observed in the control group and in patients with chronic hyperplastic laryngitis. In tumor tissue, the level of РРМ1В was associated with the size of the primary tumor and the presence of metastases. In tumor tissue, the level of РРМ1В was also higher in patients with stage T1N0M0 than in patients with chronic hyperplastic laryngitis. The data obtained indicate that the level of РРМ1В can be used for early detection and prediction of the clinical course of SCHNC. Further studies with larger cohorts of patients are required to evaluate the prognostic significance of the РРМ1В level.

Background. Colorectal cancer is the third most common cancer worldwide. The tendency towards increased incidence of colorectal cancer in Tomsk region correlates with World and Russian tendencies. The purpose of the study was to analyze the incidence rate of colorectal cancer in Tomsk region. Material and methods. The study was based on cancer register data collected at the Cancer Research Institute and Regional Cancer Center (Tomsk) and covered the period 2005 по 2015. Demographic data were obtained from local authorities and government statistics. Results. In Tomsk region, colorectal cancer is the second most common cancer. During the study period (2005–15), the incidence rate of colorectal cancer increased by 39.9 %. The highest incidence rates were observed in patients aged 55 years and older. The median age of patients diagnosed with colorectal cancer in 2015 was 56.3 years. The female and male median age showed a decreasing tendency. In 2015, the colorectal cancer incidence rate in both females and males was the highest among the territories included into the Siberian Federal Region, being 30.9 per 100,000. The rate then stabilized in females, but tended to increase in males. The cumulative risk of developing cancer among the population of Tomsk region had increased, being 7.9 in 2015 compared to 6.5 % in 2005. The cumulative risk of developing cancer was higher in males than in females (10.1 % versus 6.9 %). A specialized care to patients with colorectal cancer over a 10-year period has improved, however one-year mortality rate remains high. The study has shown that screening programs based on the detection of occult blood in the stool are not specific enough. Colonoscopy using high-resolution endoscopy and narrow beam imaging (NBI) are recommended to use as a screening method for the detection of precancerous diseases of the colon.

Squamous cell carcinoma of head and neck (SCCHN) is often asymptomatic until it reaches the advanced stage. Currently, there are no available markers that can accurately predict the risk of progression of epithelial dysplasia to squamous cell carcinoma. The purpose of the study was to evaluate the feasibility of using the level of adenylyl cyclase-associated protein 1 (CAP-1) in the blood serum to identify groups of increased risk of cancer in patients with chronic laryngeal and hypopharyngeal hyperplasia associated with epithelial dysplasia. Material and methods. The blood serums from 45 patients with SCCHN (T1–4N0–3M0), 12 patients with chronic inflammatory laryngeal and hypopharyngeal diseases and 15 heath subjects were examined. The blood analysis was performed using the CAP1 ELISA kit (Cusabio) on the Biochrom Anthos 2020 Microplate IEA Reader. Results. The serum level of САР1 was higher by 75 % in patients with SCCHN (Т1N0M0) than in patients with chronic hyperplastic laryngitis. Moreover, differences in the serum level of САР1 were observed between healthy subjects and patients with chronic laryngeal hyperplasia. In SCCHN patients with regional metastases, CAP1 concentration in the blood serum was 2 times higher compared to that observed in SCCHN patients without regional metastases (p≤0.01). Conclusion. The study results showed the feasibility of using the level of CAP1 for distinguishing patients with chronic hyperplastic laryngitis from those with laryngeal cancer, as well as for early detection of SCCHN and the development of new method for prediction of disease.

The present study was undertaken to evaluate the incidence of pharyngeal cancer in the Tomsk region for the period between 2007 and 2015. Approximately 27 new cases of pharyngeal cancer are annually diagnosed in the region. Between 2007 and 2015, the pharyngeal cancer incidence in males was reported to be higher (80.9 %) than in females. The incidence rate of oropharyngeal cancer was 73.4 %. This incidence rate was not stable over time, and it was 2.2 per 100,000 population in 2015. In 2015, the pharyngeal cancer incidence in the Tomsk region was the highest in the Siberian Federal District (2.3 compared to 0.4) The pharyngeal cancer incidence was higher in rural than urban areas. High percentage of patients with advanced-stage disease and one-year mortality was registered in the region.

The paper presents the results of determining the concentration of specific antiviral immunoglobulins to viral antigens in blood serum of patients with gastric dysplasia (n=56) and gastric cancer (n=54), as well as the incidence of their titers depending on tumor location and histotype. In patients with precancerous gastric lesions, the increase in the IgG titer to Epstein Barr Virus (EBV) capsid antigen (VCA) and IgG to EBV early antigen (EA) in blood serum was found to be associated with enhancement of inflammatory activity. In patients with gastric cancer, high titers of IgG to VCA and IgG to EA were observed more frequently than in patients with gastric dysplasia, and the decrease in differentiation grade was followed by the increase in the concentration of IgG to EBV VCA. High titers (≥1:320) of IgG to VCA were found of patients with tumors located in the gastric body and cardia. High IgG titers to EBV VCA were shown to be associated with the presence of exophytic and ulcerated exophytic tumor growth.

The purpose of the study: to evaluate the effectiveness of postoperative management of the bronchial stump in lung cancer patients. material and methods. Forty-four patients with stage III lung cancer underwent endoscopic examination of the bronchial tree 3, 6, 9 and 12 months after surgery. The EVIS EXERAII and LUCERA videoendoscopic complexes with consistent use of white light mode, autofluorescence and narrow- spectrum mode were used. Endoscopic results were compared with morphological findings. Results. X-ray of the chest was negative for tumor recurrence in 3 (6.8 %) cases and early metachronous tumor of the trachea was revealed in 1 (2.3 %) case. The main endoscopic symptoms of early local recurrence in the bronchial stump were the marked lilac glow identified in the AFI mode and the mucosal vascular pattern deformation Timely diagnosis of recurrence allows a special treatment to be performed.

We present a clinical case of non-small cell lung cancer treated with personalized adjuvant chemotherapy. The expression levels of drug resistance genes, such as ABCC5, RRM1, ERCC1, TOP1, TOP2a, TUBB3 and TYMS in tumor tissue from non-small cell lung cancer were used as predictive markers. This case shows the usefulness of determination of the expression of drug resistance genes before and after preoperative chemotherapy, and it is important in terms of determining the individual sensitivity of the tumor to chemotherapy drugs, thus allowing the treatment plan for the individual patient to be tailored.

Tomsk region refers to the areas of increased risk of malignancies, including laryngeal and upper respiratory tract cancers, which account for 2.0 % of all cancer cases. Approximately 83 new cancer cases (70 % in males) are annually diagnosed, with a tendency to increase. In 2014, the standardized incidence rate of upper respiratory tract cancer (URTC) was 7.7 per 100,000 men and women. The incidence rate was 6.7 times higher in men than in women. Laryngeal cancer was the most common malignancy in both men (67.7 %) and women (60.0 %). The age-standardized mortality rate of laryngeal cancer was 2.7 per 100,000 of population. Among patients registered at the end of 2014, 1.1 % patients were diagnosed with laryngeal cancer and 0.3 % with pharyngeal cancer. The laryngeal cancer incidence in the Tomsk region was lower than that in the Russian Federation as a whole. The rates of laryngeal and pharyngeal cancer detection at prophylactic medical examinations remain low (5.9 % and 1.5 %, respectively), and 1-year lethality rates are high (65.2 % and 28.6 %, respectively). Introduction of the program on pre-cancer and early laryngeal cancer detection into routine clinical practice allowed us to identify diagnostic errors in 16.3% of cases, verify laryngeal cancer and to form groups at high risk for laryngeal cancer in 20.6 % of cases.

In the last decade, molecularly-targeted therapy is the most intensively developing treatment modalities in oncology. The main targets for this therapy are many elements of apoptosis signaling pathways and cell cycle regulation, the damage of which is associated with a malignant growth. One of the available molecular targets is the epidermal growth factor receptor (EGFR), which activation occurs in lung cancer, colorectal cancer, squamous cell carcinoma of the head and neck , breast cancer, melanomas, etc. To block oncogenic EGFR signaling, target drug as small molecule tyrosine kinase inhibitors, peptide associated cytotoxins and antiEGFR monoclonal antibodies were created. However, there are a number of studies (FLEX, SATURN, INTEREST, IPASS), where the expected and observed clinical cure rates of target drugs are not the same, including primary goal - increasing time to tumor progression. As the cause of inconsistency of treatment results may be lack the selection of patients with the additional molecular damages (mutations or genetic polymorphisms), providing the sensitivity and /or resistance to therapeutic agent. The most important reason for discrepancy between the real and the expected treatment effect of target drugs is the phenomenon of intratumoral heterogeneity, that is manifested as coexist of cells with different biological properties, due to genetic, epigenetic, phenotypic peculiarities of tumor clones within the tumor. Search for new driver targets and the creation of drugs directed against them, development of multitarget approach are perspective to improve the effectiveness of targeted therapy. In addition, it is important to use molecular testing to monitor the treatment efficacy, because therapy can drive the tumor clonal evolution, leading to the emergence of resistant cell clones.

We compared the serum proteome profiles of squamous cell head and neck carcinoma patients with metastases, without metastases and healthy volunteers using the combination of gradient gel-electrophoresis (1D-SDS PAGE) and mass-spectrometry. The study showed the difference in the serum proteome between healthy volunteers and squamous cell head and neck carcinoma patients with metastases and without clinical evidence of disease progression. Proteins in the serum proteome of patients with squamous cell head and neck carcinoma that participate in various cellular processes can be suggested fur further study as potential markers of cancer progression.

MicroRNA are nonprotein-coding small ribonucleic acids controlling gene expression at post-transcriptional level. MicroRNA technically could controll 2/3 of human genome. At the present study abnormal expression of microRNA-18а, -21, -155, -200а, -200с, -205, -221, -494 in malignant tissue of squamous cell larynx carcinoma of 46 patients were studied. There was no statistically significant correlation between microRNA expression and pathological characteristics. Our data showed that oncogenic microRNA-21, -155, -205 were overexpressed as well as oncosypression microRNA-200a were underexpressed in larynx cancer compared to adjacent normal epithelium.

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with long asymptomatic course. New molecular prognostic markers are urgently needed to identify patients at high risk for developing lymph node metastasis. MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs. Based on literature and our data, we have chosen 12 miRNAs (miRNA-21, -221, -222, -155, -205, -20a, -125b, -146b, -181b, -200a, -126, -451), involved in HNSCC carcinogenesis. Using real-time quantitative polymerase chain reaction analysis, we have shown a change in the expression miRNA in tumor tissue compared to unmodified tissue. Significant upregulation of five miRNAs: miRNA-21, -155, -181b, -126, -451 (p

The paper presents two-year results of combined modality treatment of patients with stage III–IV (T3N0–1M0) locally advanced laryngeal and laryngopharyngeal cancer. In the first phase of the treatment, all 24 patients included into the study, received preoperative RT with local hyperthermia. Preventive tracheostoma was not an obstacle for the treatment. Patients who achieved partial response or stable disease underwent surgery. In case of complete tumor regression (n=5), radiotherapy was continued up to the total dose of 66 Gy. Histological examination of surgical specimens revealed complete pathological response in all patients who received combined modality treatment. Regional metastases were revealed in 2 patients, and they subsequently underwent lymph node dissection. The overall 2-year survival rate was 100 % and 2-year metastasis-free survival was 91.7 %.

Cancer of the larynx and laryngopharynx, which is accessible to visual and instrumental examination, remains the most relevant and complicated problem among head and neck malignances as before. Investigations show that the incidence of cancer at these sites in Russia in the last decade has risen from 4.5 to 9.67 %. This is a severe and poor prognostic form of cancer, which is characterized by its nonspecific early clinical manifestations, complex anatomic and topographic structure, and a high rate of regional metastases. The mainstay of treatment for head and neck cancer involves 3 components: surgery, chemotherapy, and radiotherapy (RT), which are performed alone or in combination. The most commonly used technique is combined, frequently crippling due to organ-removing operations. The clinical introduction of current radio modifiers, local and deep hyperthermia systems, is a promising approach to improving the results of treatment, to enhancing the radiation damage of RT, and to achieving the tumor regression sufficient for surgical intervention without augmenting the early and late toxicity inherent in chemoradiation treatment. The results of the performed study of 35 patients with T2–3N0–2M0 laryngeal and laryngopharyngeal cancer proved the high efficiency of local hyperthermia in treating malignancies in this region during both preoperative (grades III– IV therapeutic pathomorphism) and radical beam RT.

Abstract. The aim of present study was to evaluate the influence of HPV infection on lymphogenic metastasis and survival of patients with head and neck squamous cell carcinoma. DNA was isolated from tumor tissue and tumor-adjacent normal epithelium of 64 patients with head and neck tumors of different localization. Detection of 12 HPV genotypes was carried out by the PCR using AmpliSens diagnostic kits (Russia). The association between HPV infection and clinical-pathological parameters of the patients was assessed. HPV was detected in tumor tissue and in the surrounding normal tissue in 22% of patients. The most common HPV genotypes were 16 and 51. No association of HPV infection with sex, age, location, TNM stage and differentiation grade was found. The Kaplan Meier method showed a tendency towards the improvement of the overall and recurrence-free survival of HPV-positive patients with head and neck cancer (p = 0.09 and p = 0.12 respectively). The multivariate survival analysis using Cox’s regression model showed that the patient’s age and the presence of lymph node metastases (p = 0.002) significantly influence on patient survival (p = 0.014 and p = 0.002 respectively).

A complex heterogeneous process of ion exchange can be defined with an isotherm-isobar equation of the chemical reaction, which describes differential affinity between the process and its effect – the law of mass action. Ion exchange includes processes accompanied by changes in the charge of ions and functional groups caused by the passing of ionic bond into covalent one. Hence isotherm equations of ion exchange for such processes must differ from conventional stoichiometric equations, but they can be obtained by classical study approaches to ion exchange equilibrium. The paper describes a new thermodynamic model, based on linearization of mass action law, modified for the ion exchange equation. The application of this model allows to define stoichiometry of ion exchange and the shape of ions adsorbed by the solid phase of ion-exchange resins, as well as to estimate equilibrium constant and Gibbs free energy of the process. Comparative analysis has been carried out for the thermodynamic model of cerium sorption in the form of anionic complex with Trilon B from a multisalt solution with ionic strength of 1 mol/kg (NaNO3) under рН = 3 and temperature 298 K on a test sample of weak-base anion-exchange resin Cybber EV009. Experimental isotherm of the sorption has been obtained. Calculations of thermodynamic parameters have been performed using Langmuir, Freundlich, Dubinin – Radushkevich, Temkin and Flory – Huggins models, as well as thermodynamic model of linearized mass action law, proposed by the authors. Calculated values of the equilibrium constant and Gibbs energy – K = 9.0±0.5 and ΔrG0298 = –5.54±0.27 kJ/mol – characterize the sorption of EDTA cerate ions by ion-exchange resin. The shape of adsorbed ions has been defined in Stern-Helmholtz layer of CeTr, and total capacity of anion resin EV009 for EDTA cerate ions has been estimated as q∞ = 2.0±0.1 mol/kg.

The concentrations of matrix metalloproteinases (MMP-2, -3, -9) and their tissue inhibitors (TIMP-1, -2) were studied in blood serum of 193 patients with squamous cell head and neck carcinoma (SCHNC) and in 38 healthy donors using immunoenzymatic assay. The decreased MMP-3 and TIMP-1, -2 levels were found in patients with oral cavity tumors as compared to patients with laryngeal cancer. The serum MMP-9 and TIMP-1 levels were significantly higher in head and neck cancer patients than in healthy subjects. High TIMP-1 and MMP-9 levels in blood serum of patients with SCHNC should be greatly attended for detection of their predictive and prognostic significances.

Modern gas analysis requires an integrated approach to ensure the necessary metrological characteristics and achieve high reliability of detection. A new algorithm for multisensor systems based on synthesized domestic materials possessing semiconductor properties has been developed for the analysis of a wide range of gases of metallurgical industries. The use of gas-sensitive elements made of semiconductor material with n-type conductivity allows solving the main task of modern gas analysis – detection of vapors and gases of a wide range with high stability, necessary selectivity and sensitivity. Due to the developed surface structure formed from polycrystals 3-10 nm in size, semiconductor sensors allow to detect various substances in air in a wide range of concentrations: from trace amounts of 10-6-10-5 mg/m3 to high 500-800 mg/m3. Increase of the selectivity of the sensors is facilitated by the introduction of catalysts into the gas-sensitive layer of doping impurities. The formation of multisensory systems increases degrees of freedom, expanding the range of identification of the analytes. In addition to solving the analytical task of forming gas sensitive elements, digital circuit and aerodynamic solutions have been developed that meet the requirements of gas analysis in a wide range of impurity concentrations and application conditions.