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Background. Colorectal cancer (CRC) is one of the most common cancers and one of the most leading causes of cancer-related deaths worldwide. Approximately 35 % of CRC patients have liver metastases at the time of diagnosis. These patients have a poor prognosis, with the 5-year survival rate of 15 %. Given the poor survival with currently approved methods, the development of the optimal treatment options is needed.The purpose of the study was to search for data on the development of surgical techniques for the treatment of patients with metastatic CRC (mCRC) with isolated liver metastasis.Material and Methods. Literature search was carried out in Medline, Cochrane Library, Elibrary and Pubmed databases, including publications characterizing historical and modern results (from 1976 to 2021).Results. Liver resection in mCRC patients with isolated liver metastasis is the only treatment that offers a chance of increasing the 5-year survival rate up to 45–60 %. Radical surgery should include the removal of the primary tumor and all metastases with negative histological resection margins while preserving sufficient functional liver parenchyma. The paper discusses various approaches to surgical treatment of mCRC patients with liver metastases, with an assessment of their advantages and disadvantages, as well as presents data on perioperative and oncological outcomes.Conclusion. The surgical treatment strategy should be adapted for each mCRC patient with synchronous liver metastases. The core function of a multidisciplinary team is to determine the patient’s treatment plan combining surgery and systemic chemotherapy, which will improve the immediate and long-term treatment outcomes.

Background. Pancreatic cancer is characterized by pronounced invasive growth and a high tendency to lymphogenous and hematogenous metastasis. Molecular mechanisms underlying the epithelial-mesenchymal transition, in particular, changes in the expression of β1, β3 integrins and MMP2, contribute to the invasion and metastasis of pancreatic cancer. A phenotypic manifestation of invasive potential of pancreatic cancer may be the heterogeneity of the morphological structure of the parenchymal component of ductal adenocarcinoma.The aim of the study was to analyze the expression levels of β1 integrin, β3 integrin, MMP2 and the morphological heterogeneity in the tissue of pancreatic ductal adenocarcinoma, as well as to compare the data obtained with distant metastasis.Material and Methods. The study group included 84 patients with morphologically verifed pancreatic ductal adenocarcinoma (T1–4N0–2M0–1). The median age of the patients was 58.6 ± 9.1 years. All patients underwent surgery, during which an incisional biopsy of the primary tumor tissue was performed. Expression of integrin β1, integrin β3, and MMP2 markers was assessed by immunohistochemistry.Results. The positive expression of β3 integrin in glandular, trabecular, and solid structures was observed more frequently in patients with hematogenous metastases than in patients without distant metastases (87 vs 12 %, р=0.001; 100 vs 22 %, р=0.004; 100 vs 8 %, р=0.001, respectively). The positive expression of MMP2 in glandular and solid structures was also observed more often in patients with hematogenous metastases than in patients without distant metastases (87 vs 32 %, р=0.001 and 100 vs 27 %, р=0.001, respectively). The positive expression of integrin β1 in glandular, trabecular, solid structures and tumor cells was observed less frequently in patients with hematogenous metastases than in patients without distant metastases (27 vs 86 %, р=0.001; 25 vs 79 %, р=0.007; 0 vs 93 %, р=0.001 and 18 vs 60 %, respectively). The logistic regression model for predicting the risk of hematogenous metastasis of pancreatic ductal adenocarcinoma was developed: Y=(-6.71 + 30.9×X1 – 27.2×X2), where X1 – the presence or absence of β3 integrin expression in the cells of the glandular structures, X2 – the presence or absence of MMP2 in the cells of the glandular structures. The risk of developing hematogenous metastasis was determined by the formula: Р=еY/(1+еY). Model confdence interval: χ2 =34.0; p ˂ 0.001, sensitivity: 89 %, specifcity: 87 %.Conclusion. Expression of integrin β1, integrin β3, and MMP2 markers in various structures of the parenchymal component of pancreatic ductal adenocarcinoma is associated with distant metastasis. The localization of the expression of the studied markers in the glandular structures of tumor tissue is of particular importance. The presence of positive expression of integrin β3 and MMP2 in almost all types of tumor structures is associated with the highest frequency of distant dissemination.

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.

Aim of the study: a systematic analysis of the modern literature data on the nivolumab monotherapy efficacy in patients with metastatic colorectal cancer (mCRC). Material and methods. The review summarizes the results of clinical studies of the nivolumab efficacy in patients with mCRC between 2012 and 2022. The current approaches to assessing the tumor response in patients treated with immune checkpoint inhibitors are considered, including response patterns and criteria. Results. Data analysis showed that the use of nivolumab in mCRC patients had significant clinical benefits. Nivolumab monotherapy was shown to improve survival in patients with high microsatellite instability (MSI) or deficiencies in mismatch repair (dMMR) that progressed during standard chemotherapy. Numerous clinical studies indicate the atypical response to nivolumab. Traditional response criteria, such as RECIST do not always adequately assess the therapeutic efficacy of nivolumab in patients with mCRC. Conclusion. To improve the efficacy of mCRC treatment, standardized approaches based on the proposed specific criteria for response to immunotherapy, including immune related RECIST, immune RECIST, and immune-modified RECIST must be developed.

The treatment of colon cancer with a mesenchymal-like phenotype poses a great challenge. Purpose of the study: to research expression of FRMD6, ZEB1, HTR2B, CDX2 in the primary tumor tissue with relation of the clinical and pathological features of colon cancer. Material and methods. a combined analysis of the expression of FRMD6, ZEB1, HTR2B, CDX2 with pathological criteria was performed in 100 patients with T1–4bN0–2bM0 colon cancer. Results of the study show that tumors with mesenchymal signs are characterized by a large size of the primary tumor, a high grade of differentiation, regional metastases, and eventually advanced stage of the disease. The frequency and expression levels of FRMD6, ZEB1 and HTR2B are depended of grade of adenocarcinoma. in cases with positive expression and a high percentage of expression of these proteins in the cancer cells, the degree of tumor morphological anaplasia increases. Conclusion. The study made it possible to reveal the relationship of IHC markers (FRMD6, ZEB1, HTR2B, CDX2) with tumor characteristics that determine the outcome. The studied markers may have prognostic and predictive value in treatment approaches of colon cancer.

Introduction. Currently, most of the drugs used in tumor therapy are highly toxic and cause various toxic effects. Therefore, many drug delivery methods are being developed. The use of nanotechnology is one of the most promising methods. The use of magnetic iron oxide nanoparticles as antitumor agents makes it possible to prevent off-target cytotoxicity and other side effects of traditional chemotherapy. The use of nanoparticles is limited by their low efficiency. the Fe3O4/Fe galvanic couple makes it possible to control the release of toxic iron ions and, accordingly, the activity of nanoparticles. Purpose. The aim of this study is to develop new Fe3O4-Fe nanoparticles with a core-shell structure with antitumor activity in vitro. Nanoparticles containing from 5 % to 90 % iron were synthesized, and a systematic study of the structural, textural, charge, morphological, and magnetic properties of nanoparticles, as well as their in vitro activity against the MCF-7 and HeLa tumor lines, was carried out. Methods. Fe3O4-Fe nanoparticles were obtained by electric explosion of an iron wire in a mixture of gases: argon and oxygen. The mass fraction of the components was regulated by varying the ratio of the components of the gas mixture. The physicochemical properties of nanoparticles were studied using X-ray phase analysis, thermal desorption of nitrogen, transmission electron microscopy, and microelectrophoresis. Antitumor activity was studied using the MTT test against HeLa and MCF-7 cell lines. Results. As a result of the electric explosion of an iron wire in an argon + oxygen gas mixture containing oxygen in the range of 1 – 5 vol. %, Fe3O4-Fe NPs with 5 – 90 % wt. Fe3O4, respectively. The study of the physicochemical properties of nanoparticles showed that the zeta potential does not depend on the content of Fe3O4 in NPs and is -30 mV. The change in the specific surface area and the average particle size passes through a maximum at the content of Fe3O4 W=20 %, which can be explained by the mechanism of oxide phase formation during an electric explosion. Using the MTT test, it was found that nanoparticles containing 5 wt. Fe3O4, in the presence of which, at a concentration of 1 mg/ml, the number of living cells decreased to 16 % relative to the control. Conclusion. In this work, we have shown for the first time that Fe3O4-Fe NPS in the concentration range of 50–100 µg/mL can be used as an antitumor agent. The ability to control the magnetic properties of NPs can be used to target a specific area of tumor tissue using an external magnetic field, and the established relationship between the magnetic moment and the activity of NPs in relation to the MCF-7 cell line has great prospects for clinical application.

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.

Background. Currently, the use of nanoparticles and nanostructures as components of tumor therapy is the subject of numerous scientific articles. To change the parameters of cell microenvironment in presence of nanoparticles and nanostructures is a promising approach to reducing the tumor cell viability. Aluminum hydroxides and oxides have a number of advantages over other particles due to their porous surface, low toxicity, and thermal stability.The purpose of the study was to investigate the influence of the acid-base properties of aluminum hydroxide structures with different phase composition on the tumor cell viability (Hela, mda, pymt, a549, B16F10).Material and methods. Aln/al nanoparticles were used as a precursor for obtaining structures with various phase compositions. The anoparticles were produced by electric explosion of an aluminum wire in a nitrogen atmosphere. Such nanoparticles interact with water at 60 °Ϲ, resulting in formation of porous nanostructures. They are agglomerates of nanosheets with a planar size of up to 200 nm and a thickness of 5 nm. The phase composition of the structures was varied by the calcination temperature. A change in the phase composition of nanostructures led to a change in the acid-base properties of their surface. To estimate the number of acidic and basic centers on the surface of nanostructures, the adsorption of Hammett indicators was used. The amount of adsorbed dyes was determined spectrophotometrically.Results. It was found that the differences in the acid-base characteristics of the surface of the nanostructures led to a change in their antitumor activity. Γ-al2o3 had 6.5 times more basic centers than acidic ones, which determined its ability to exhibit more pronounced antacid properties, i.e. Longer to neutralize protons secreted by tumor cells. This sample had the highest antitumor activity against all tested cell lines.Conclusion. The antitumor activity of synthesized structures was found to be related not only to an increase in the ph of the cell microenvironment, but also to the ability to maintain the alkalinity of the microenvironment for a longer time due to the adsorption of protons released by tumor cells.

Purpose of the study: to review the available data on the heterogeneity of colon cancer and to assess the prognostic significance of colon cancer subtypes.Material and Methods. Medline, PubMed, Cochrane library, elibrary databases were used to identify studies that characterized the current view on the problem of choosing the optimal postoperative treatment for colon cancer.Results. the review showed the results of international studies of colon cancer subtypes based on complex multomics characteristics. Particular attention was paid to the description of modern studies on the search for prognostic markers for colon cancer. The relevance of the study of immunohistochemical markers was confirmed by the analysis of the world literature. the outcomes will make it possible to classify colon cancer into molecular subtypes in real clinical practice and, as a consequence, significantly improve the effectiveness of adjuvant therapy.

The purpose of the study was to analyze and summarize data regarding a significance of PD -L1 expression in various molecular subtypes of colorectal cancer.Material and Methods. A systemic literature search was conducted in the electronic databases Medline, Cochrane Library, Elibrary, PubMed. Of identified and reviewed 201 full-text articles, we included data from 47 studies.Results. The literature review described the features of the molecular genetic classification of colorectal cancer and revealed the key characteristics of each of the molecular subtypes of this disease. Much attention was paid to the molecular mechanisms of anti-PD -1/PD -L1 therapy. The main problems associated with the standardization of methods for pathomorphological assessment of the expression of this marker and the difficulties of its interpretation in colorectal carcinomas were outlined.Conclusion. Analysis of the literature revealed problems associated with the assessment of PD -L1 expression in colorectal cancer, in particular, with the lack of generally accepted methods for interpreting research results and standardizing methods for pathomorphological diagnosis of malignant tumors of this localization. Further studies are needed for introducing the molecular genetic classification of colorectal carcinomas into a wide clinical practice and personalizing the approach to therapy of this disease.

Primary gastrointestinal melanoma is a rare tumor with a frequency of 1 new case per 5–7 years. Over the past 100 years, there have been no more than 25 reported cases of primary melanoma of the stomach and colon. The rarity of the disease and nonspecific clinical features pose diagnostic challenges. The tumor is characterized by an aggressive growth and early metastasis. Case description. We present a rare clinical case of primary gastrointestinal melanoma with metastatic involvement of the adrenal glands, liver and retroperitoneal lymph nodes. Conclusion. To date, treatment standards for primary gastrointestinal melanoma have not been developed and are the subject of debate. However, palliative chemotherapy used for the treatment of primary skin melanoma may lead to disease stabilization in patients with gastrointestinal melanoma.

A multicenter randomized trial was conducted to assess histopathological response to neoadjuvant chemoradiotherapy in patients with locally advanced gastric cancer.Material and Methods. Patients of the study group received conformal radiation therapy (total dose of 46 Gr/23 fractions) with concurrent chemotherapy consisted of capecitabine at a dose of 1850 mg/m2 twice daily during the whole course of radiotherapy, and oxaliplatin at a dose of 85 mg/m2 on days 1 and 21. After an interval of 4–6 weeks and a control examination, in the absence of disease progression, patients were scheduled for surgery (gastrectomy or D2 subtotal gastric resection) and 4 cycles of adjuvant chemotherapy according to the FOLFOX4 or CAPOX regimens.Results.The study included 70 patients, including of 35 patients in the study group. Men predominated (n=23), the age ranged from 22 to 76 years (median – 61 years). The middle third of the stomach was the most common tumor location (n=19); involvement of the entire stomach occurred in 5 cases. Ulcerative and diffuse infiltrative forms were the most common (n=29). Well-and moderately-differentiated adenocarcinoma was observed in 11 patients and poorly – differentiated adenocarcinoma in 24 patients, including signet ring-cell cancer (n=8). In accordance with the clinical T, N and M categories, patients were distributed as follows: T3 – 22 patients, T4a/b – 13; N0 – 13, N1 – 12, N2–3 – 10; M0 – 35; stage IIB – 12, and stage III–IVA – 23 patients. Gastrectomy was performed in 30 patients and subtotal resection of the stomach in 4 patients; D2 lymphodissection was performed in all cases. One patient was not operated on due to disease progression. Of the 47 patients achieving pathological response, 5 (14.7%) patients had a complete pathological response. Among patients achieving pathological response, a statistically significant predominance of less advanced tumors was found (in accordance with the ypT category and stage).Conclusion. In general, a decrease in the pathological tumor stage compared to clinical stage was registered in 62 % of patients. Taking into account the data available in the world literature on high survival rates in patients with pathological complete regression, the optimization and implementation of neoadjuvant therapy techniques is of great importance.

Introduction. There are high-thech methods of nanoparticle production with controlled morphology and physical and chemical properties. Alumina-based mesoporous nanostructures have low toxicity and biocompatibility. FDI recommends alumina for biomedical application. Alumina inhibits the grow of cancer due to positive zeta-potential and low solubility in water. We observed the synergistic effect of joint application of doxorubicin and nanostructures. This approach reduces drug concentration and its toxicity.Purpose: to synthesize nanostructures with different surface potentials and to study toxicity of these nanostructures alone and in combination with doxorubicin.Material and Methods. The alumina-based nanostructures were obtained by the hydrolysis of nanopowder. The morphology of nanostructures was investigated by transmission electron microscopy with an integrated system of energy dispersive analysis. The phase composition of the particles was determined by x-ray diffraction. The effect of the synthesized nanostructures on the viability of cell lines was determined using the MTT test.Results. The synthesized nanostructures have a low toxicity and can be used as an adjuvant for doxorubicin.Conclusion. The combined use of doxorubicin and bicomponent nanostructures leads to an increase in the damaging effect of doxorubicin on Neuro-2a cells.

Introduction. Stomach cancer remains one of the most common malignancies with an unfavorable prognosis. It is the 5-th most frequent cancer and the 3rd leading cause of cancer death worldwide and in Russia as well. Combined modality treatment including radical surgery and perioperative / adjuvant therapy is the current therapeutic strategy for locally advanced gastric cancer. New approaches to combined modality treatment including neoadjuvant chemoradiotherapy for locally advanced gastric cancer were developed at A. Tsyb Medical Radiological Research Center (Obninsk, Russia) and tested in a phase 2 randomized clinical trial. The results obtained showed the safety and high efficiency of the method. To objectify the results, a multicenter randomized trial was initiated in 2016. the main objective of the study was to assess the immediate efficacy and safety of neoadjuvant chemoradiotherapy using pathological response criteria and to evaluate the frequency/severity of toxic reactions and postoperative complications. Additional objectives of the study were to assess the accuracy of preoperative staging of gastric cancer; tumor regression grade of the primary tumor and regional lymph node metastases according to CT findings; treatment outcomes according to the criteria of frequency and time to recurrence/metastasis; 1-, 2 -, and 3-year survival rates. Material and methods. The study included 70 patients with equal distribution between the treatment groups. There were more males than women; the median age was 62 years. The main criterion for inclusion of patients into the study was morphologically confirmed gastric cancer of сT2–4N1–3, сT3–4N0–3; сМ0, IIA-IIIC stages. Patients of the first (investigated) group were treated with neoadjuvant chemoradiotherapy (total dose of 46 Gy in 23 fractions and chemotherapy with capecitabine and oxaliplatin) followed by surgery (gastrectomy/subtotal resection of the stomach with D2 lymph node dissection) and 4 cycles of adjuvant chemotherapy. Patients of the second (control) group underwent surgery (gastrectomy/subtotal resection of the stomach with D2 lymph node dissection) followed by 6 cycles of adjuvant chemotherapy. Results. The tumor was localized in the middle and lower thirds of the stomach in most cases. There were mostly low-grade adenocarcinomas (47 patients). None of the patients showed the presence of distant metastases; 2B and 3 clinical tumor stages were mostly observed. The comparison of clinical and pathomorphological stages in the control (surgical) group showed that a comprehensive examination, including CT and laparoscopy, allowed the correct assessment of the tumor stage and formation of the control group according to the main inclusion criteria in more than 90 % of patients. Comparison of patients between the study and control groups showed that they were well balanced on the main prognostically important factors. The differences between all parameters were not statistically significant (p>0.05).

intraduction . Gastric cancer is the most prevalent malignancy in the world. the common metastatic sites of gastric cancer include liver, lymph nodes and peritoneum. testicular metastasis from gastric cancer occurs extremely rare. there are only 15 reports in literature describing cases with testicular metastasis from gastric cancer. Case report. We first report a clinical case of a man presented with metastasis in the left testis and locally advanced gastric cancer. the patient underwent gastrectomy with resection of the transverse colon and left-sided orchofuniculectomy. Postoperative morphological and immunohistological examinations revealed gastric cancer with metastasis into the testis. He had received 6 cycles of chemotherapy, with no evidence of recurrence within a 9-month follow-up period.

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.

Introduction. Cutaneous melanoma is a challenge to treat due to rapid progression of disease and acquired resistance to therapy. Autophagy and the epithelial-to-mesenchymal transition (EMT) are closely interrelated and play a key role in tumor progression. Targeted co-inhibition of MEK and mTOR kinases is a potential target for melanoma therapy by downregulatoin of the EMT.Objective: to study the effect of MEK and mTOR co-inhibition on cell viability, ability to form 3D-spheroids and migratory capacity of melanoma cell lines, and correlation of these changes with EMTand autophagy-related markers.Material and Methods. Melanoma cell lines Mel Z and Mel MTP were derived from patients, who were treated at the N.N. Blokhin National Medical Research Center of Oncology. The antiproliferative effect of binimetinib and/or rapamycin was studied by the MTT -test. 3D spheroids were formed using RGD peptides. Cell migration and invasion were assessed by a Boyden chamber migration assay. The expression levels of autophagy and EMT markers were investigated by immunocytochemistry or immunoblotting.Results. Rapamycin increased cytotoxicity of binimetinib in both 2D and 3D melanoma cell line cultures. At the same time, binimetinib and rapamycin reduced invasion, but not migration capacity of melanoma cells in vitro. The effectiveness of the combination was associated with a decrease in the EMT markers (N-cadherin and β-catenin) and autophagy markers (Beclin 1, p62/SQST M1 and LC3BII ) in melanoma cells.Conclusion. Inactivation of autophagy and EMT leads to overcoming the resistance to current anti-melanoma therapy and can be considered as a promising target for the treatment of melanoma.

Background.Currently, the indications for multivisceral pelvic resections have increased dramatically. However, short-and long-term outcomes after these resections for locally advanced rectal cancer remain a subject of debate.The purposeof the study was to evaluate short-term surgical and oncological outcomes after multivisceral pelvic resections in patients with locally advanced rectal cancer.Material and methods. We analyzed surgical outcomes in 32 patients (13 men and 19 women) aged 44-69 years, with locally advanced rectal cancer, who were treated between 2010 and 2016. Of the 32 patients, 28 (87.5 %) had rectal cancer with invasion into adjacent organs (posterior wall of the bladder - 13, uterus - 10, ureters - 5, prostate - 4, vagina - 3; simultaneous damage to more than 2 organs - 14, multiple primary malignant tumors: rectal cancer + bladder cancer - 2, rectal cancer + endometrial cancer - 1, rectal cancer + rectal GIST - 1.Results.Total pelvic evisceration was performed in 6 (18.8 %) cases, combined resection of the rectum and adjacent organs was performed in 26 (81.2 %). Urinary tract resection was performed in 24 (75.0 %) patients. Of these patients, 13 (40.6 %) had primary plasty of the bladder and/or ureters. Postoperative surgical complications were observed in 11 (34.4 %) patients, of whom 7 (21.8 %) patients needed re-surgery. In 1 patient (3.1 %), who died in the early postoperative period, the cause of death was thrombosis of the right iliac vessels with subsequent acute renal failure. For patients with locally advanced rectal cancer, long-term outcomes were as follows: the overall and recurrence-free 2-year survival rates were 75 % and 56.3 %, respectively. All patients with multiple primary malignant tumors were alive with no evidence of disease recurrence at a follow-up of >24 months.Conclusion.Multivisceral resection in patients with locally advanced rectal cancer is a complex surgical procedure requiring the multidisciplinary team of surgeons. Despite high operative morbidity, proper perioperative management of the patients helps to achieve satisfactory immediate treatment outcomes. Long-term outcomes allowed us to consider such resections as a method of choice for locally advanced and multiple primary rectal cancers.

Preservation of the rectal sphincter during surgery for rectal cancer is necessary in order to maintain control of bowel function. For this purpose, novel approaches for combining sphincter-saving surgeries with neoadjuvant radiotherapy regimens are extensively developed. There are active discussions on the effectiveness of radiosensitization with the inclusion of chemical and physical components, one of which is local hyperthermia. This article reviews the worldwide experience in treating rectal cancer patients using local hyperthermia combined with radiation therapy. A wide variety of methods, as well as facilities for the procedure, is discussed. It should be noted that the selection of patients with rectal cancer for thermochemoradiotherapy and the choice of optimal irradiation volume remain a challenge.

The purpose of the study was to evaluate the anesthetic effect of the combination of xenon and dexmedetomidine during surgery for gastric cancer. Material and methods. The prospective randomized study included 53 patients with operable II–III stage gastric cancer. The age range was from 26 to 75 years. The patients underwent gastrectomy (n=21) and subtotal distal gastrectomy (n=32). The study group comprised 27 patients who received anesthesia with xenon and dexmedetomidine combined with epidural analgesia. The control group consisted of 26 patients who received anesthesia with sevoflurane in combination with epidural analgesia. Intraoperative patient monitoring was performed according to Harvard intraoperative monitoring standards. Plasma levels of ACTH, STH cortisole, IL-1β, IL-6, and CRP as well as cytokine profile were used to evaluate the effect of two anesthetic methods. Results. In the perioperative period, the combination of xenon and dexmedetomidine in combination with epidural analgesia was characterized by significant inhibition of systemic inflammatory reactions and a lower release of stress hormones as components of a surgical stress response expressed by a lower level of pro-inflammatory cytokines and somatotropic hormone. The frequency of postoperative inflammatory complications was lower in the xenon group than in the control group. Conclusion. The use of the combination of xenon and dexmedetomidine during surgery for gastric cancer provides a more adequate course of the perioperative period.

Objective. To compare the functional activity of natural killer cells in peripheral blood and ascites from patients with different stages of colorectal and ovarian cancers and benign ovarian tumors. Material and methods. The study included 10 patients with stage IIIC ovarian cancer (FIGO, 2009), 5 patients with benign ovarian tumors (BOTs), and 15 patients with colorectal cancer (T2–4N0–2M0 ). The control group consisted of 5 healthy donors. To evaluate the number and functional activity of NK-cells in peripheral blood and ascites, the FACS Canto II Flow Cytometer was used. Results. In peripheral blood of patients with ovarian and colorectal cancers, the relative number of activated NK-cells capable of secreting granzyme B (GB) (CD56 + CD107a + GB + PF-) was significantly lower and the proportion of degranulated NK-cells (CD56 + CD107a + GB- PF-) was higher than those of healthy donors. Low total NK-cell counts in peripheral blood were a distinctive feature of ovarian cancer patients (p< 0.05). The proportion of activated peripheral blood NK-cells, containing granules of cytolytic enzymes GB and perforin (PF) increased with tumor growth. However, lymph node metastasis in patients with colorectal cancer did not affect the level and activation of NK-cells. The comparative analysis of NK-populations in patients with benign and malignant ovarian tumors revealed that the level of CD56 + cells was significantly higher in tumor ascites compared to peripheral blood. In patients with BTs, the levels of CD56 + CD107a + and activated CD56 + CD107a + GB-PF-degranulated cells was higher in ascites than in blood. In patients with ovarian cancer, the level of degranulated cells was higher in peripheral blood than in malignant ascites. Conclusion. The tumor cells and tumor microenvironment were found to affect the number and the functional activity of NK-cells. The accumulation of free fluid within the peritoneal cavity in patients with both benign and malignant ovarian tumors resulted in significantly decreased levels of NK-cells in peripheral blood and increased levels in ascites. The differences in the functional activity of NK-cells in ascites and peripheral blood of patients with ovarian cancer require further investigation of the lymphocyte receptor status and possibly cytokine-producing function of NK-cells.

Pancreatic cancer is one of the most unfavorable malignancies. Approximately 20 % of patients with pancreatic cancer have resectable disease at the time of diagnosis, however the prognosis of the disease in these patients remains poor, and the overall 5-year survival rate is only 5 %. The evaluation of morphological features, as well as features of the expression of markers that determine the invasive potential of such neoplasms, can serve in the future as a fundamental basis in solving problems concerning prognostic factors in pancreatic cancer. The purpose of the study was to evaluate morphological and immunohistochemical features of pancreatic ductal adenocarcinoma. Material and methods. The study included 84 patients with stage T1–4N0–2M0–1 pancreatic cancer. The age range was from 37 to 83 years. Surgery was the main treatment option. Morphological examination of surgical specimens showed that the tumor histotype corresponded to pancreatic ductal adenocarcinoma. The preparation of histological specimens and immunohistochemical staining were carried out according to standard procedures. Results and conclusion. This study allowed us to determine the features of tumor morphology, as well as the features of expression of markers associated with more pronounced invasive properties of the tumor. The results of this study may be of interest in terms of their further comparison with the parameters of various forms of progression in pancreatic cancer.

The purpose of the study was a review of available data on the role of autophagy and angiogenesis in the development, progression and prognosis of colorectal cancer. Material and methods. Databases searched were Medline, Cochrane Library and Elibrary. Of 340 studies, 48 were used to write a systematic review. Results. To date, there is a variety of prognostic markers used in the study of pathogenesis, diagnosis and treatment of colorectal cancer. The review describes the molecular mechanisms of the participation of various proteins of autophagy and angiogenesis in the pathogenesis and progression of colorectal cancer, and the potential importance of their use in clinical practice is presented. Conclusion. Many of the existing markers can be used not only in assessing the prognosis, but also sensitivity to chemotherapy. However, the contradictory results of studies with respect to certain proteins require further study, validation, and subsequent introduction into practice.

The review presents the mechanisms involved in the biological behavior of rectal cancer cells. The tumor response to neoadjuvant chemoradiotherapy was evaluated. The characteristics of proliferative activity, apoptosis, cell adhesion, and migration of rectal cancer cells influenced by chemotherapy were described. The relationship between molecular genetic markers and prediction of response to chemoradiation in rectal cancer was shown.

Introduction. Stomach cancer remains one of the most common malignancies with an unfavorable prognosis. It is the 5-th most frequent cancer and the 3rd leading cause of cancer death worldwide and in Russia as well. Combined modality treatment including radical surgery and perioperative / adjuvant therapy is the current therapeutic strategy for locally advanced gastric cancer. New approaches to combined modality treatment including neoadjuvant chemoradiotherapy for locally advanced gastric cancer were developed at A. Tsyb Medical Radiological Research Center (Obninsk, Russia) and tested in a phase 2 randomized clinical trial. The results obtained showed the safety and high efficiency of the method. To objectify the results , a multicenter randomized trial was initiated in 2016. the main objective of the study was to assess the immediate efficacy and safety of neoadjuvant chemoradiotherapy using pathological response criteria and to evaluate the frequency/severity of toxic reactions and postoperative complications. Additional objectives of the study were to assess the accuracy of preoperative staging of gastric cancer; tumor regression grade of the primary tumor and regional lymph node metastases according to CT findings; treatment outcomes according to the criteria of frequency and time to recurrence/metastasis; 1-, 2 -, and 3-year survival rates. M aterial and methods . The study included 70 patients with equal distribution between the treatment groups. There were more males than women; the median age was 62 years. The main criterion for inclusion of patients into the study was morphologically confirmed gastric cancer of сT2–4N1–3, сT3–4N0–3; сМ0, IIA-IIIC stages. Patients of the first (investigated) group were treated with neoadjuvant chemoradiotherapy (total dose of 46 Gy in 23 fractions and chemotherapy with capecitabine and oxaliplatin) followed by surgery (gastrectomy/subtotal resection of the stomach with D2 lymph node dissection) and 4 cycles of adjuvant chemotherapy. Patients of the second (control) group underwent surgery (gastrectomy/subtotal resection of the stomach with D2 lymph node dissection) followed by 6 cycles of adjuvant chemotherapy. R esults . The tumor was localized in the middle and lower thirds of the stomach in most cases. There were mostly low-grade adenocarcinomas (47 patients). None of the patients showed the presence of distant metastases; 2B and 3 clinical tumor stages were mostly observed. The comparison of clinical and pathomorphological stages in the control (surgical) group showed that a comprehensive examination, including CT and laparoscopy, allowed the correct assessment of the tumor stage and formation of the control group according to the main inclusion criteria in more than 90 % of patients. Comparison of patients between the study and control groups showed that they were well balanced on the main prognostically important factors. The differences between all parameters were not statistically significant (p>0.05).