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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.

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.

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.

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.

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 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.

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.