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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.

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.

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.

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. 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.

Kartagener Syndrome (CS) is a rare autosomal recessive disease that is a part of primary ciliary dyskinesia (PCD), and is characterized by a triad of syndrome including bronchiectasis, polysinusitis and a complete mirror arrangement of the internal organs of the chest and abdominal cavities (situs inversus). In most patients, bronchiectasis in the lungs develops from the first years of life and progresses in time. The tardy diagnostic leads to a poor prognosis of the disease and adduce the development of persistent violations of the function of external respiration. Most often, patients with CS are observed by physicians and pulmonologists from early childhood, since respiratory infections often require annual hospitalization in specialized medical institutions due to abnormalities of the ciliary epithelium of the respiratory tract. However, to date, there are no generally accepted recommendations for the management and treatment of patients in this category. This article describes the case of a newly diagnosed CS in an older patient undergoing surgical treatment for gastric cancer. Despite the pronounced concomitant pathology on the part of the bronchopulmonary system, the perioperative period in the patient proceeded relatively satisfactorily and did not entail an increase in the length of hospitalization.

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.

The purpose of the study was to immediate results of neoadjuvant chemoradiotherapy in patients with locally advanced gastric cancer were analyzed in a multicenter randomized trial. Material and Methods. The comparative analysis of neoadjuvant chemotherapy regimens, toxicity and postoperative complications was carried out. Patients of the study group received conformal radiation therapy (46 Gy in 2 Gy daily fractions) concurrently with chemotherapy with Capecitabine at a dose of 1850 mg/m2 divided in two equal doses during the course of radiation therapy, 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 evident disease progression, patients were scheduled for surgery (gastrectomy or subtotal gastrectomy with D2 lymph node dissection) and 4 cycles of adjuvant chemotherapy according to the FOLFOX4 or CAPOX regimen. The treatment program for patients in the control group included surgery (gastrectomy or subtotal gastrectomy with D2 lymph node dissection) after randomization, and 6 cycles of adjuvant chemotherapy using the same regimens. The study included 70 patients with an equal distribution between groups. Results. Among the patients of the study group, grade 1 and 2 toxicity was the most common; grade 3 toxicity occurred in 9 cases; grade 4 and 5 toxicity was not observed. Among the manifestations of hematological toxicity, thrombocytopenia and leukopenia were the most common (57–60 % of patients), and grade 3 hematological toxicity was observed in 6 (17.1 %) cases. Among the manifestations of gastrointestinal toxicity, nausea, vomiting and decreased appetite prevailed; grade 3 toxicity was observed only in 3 (8.6 %) cases. The radiation component of neoadjuvant therapy was completed in 32 (91 %) patients. Both protocol-prescribed oxaliplatin infusions were performed in 34 (97 %) patients. Changes in capecitabine administration were required in 8 patients. Immediately before surgery, some patients had grade 1–2 toxicity, which did not prevent performing surgery. There were no statistically significant differences in the frequency and severity of complications in the early postoperative period between the comparison groups. Grade 1–2 postoperative complications were the most common.

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.

Due to the lack of specific symptoms of colon lipoma, the disease is often complicated by invagination, bleeding, or colonic obstruction. The article presents a clinical case of successful treatment of complicated lipoma of the hepatic flexure of the colon.

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 purpose of 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.

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.

Angiogenesis (neoangiogenesis) characterized by the formation of new blood vessels from pre-existing vessels is the main condition for the intensive growth of the primary tumor. This process is characterized by a sequence of events beginning with vasodilation, separation of pericytes from the vascular wall with subsequent proliferation of endotheliocytes and formation of vascular glomeruli surrounded by stromal cells. Evaluation of the density of microvessels, as well as «vascular kidneys» (clusters of endotheliocytes) is the most widely used method for quantifying intracellular angiogenesis. The purpose of the study was to analyze the expression characteristics of markers of neoangiogenesis (CD34 and VEGFR) in tumor tissue and to evaluate their relationship with the parameters of lymphogenous metastasis in colorectal cancer. Material and methods. Surgical specimens from 130 patients with ypT1–4N0–2M0 stage of rectal cancer, who were treated at the Thoracic and Abdominal Department of Tomsk Cancer Research Institute, were analyzed. The standard techniques for histological and immunohistochemical examinations were used. Diagnose was made according to WHO classification (2010). The study included only cases with rectal adenocarcinoma. Results. When studying the density of microvessels and «vascular budding» in a tumor tissue using an antibody to CD34, it turned out that the density of microvessels in the submucosal layer of the rectum was higher in cases with the presence of lymphogenous metastases than in cases without lymphogenous metastasis. The microvessel density determined by the antibody to VEGFR in the mucosa, submucosal and muscle layers, as well as in the serosa of the rectum did not differ between groups with the presence or absence of lymphogenous metastases. The density of «vascular kidneys» in all layers of the rectum wall was not associated with lymphogenous metastasis. Conclusion. The study showed that the expression of molecular-biological markers of neoangiogenesis in tumor tissue of patients with rectal adenocarcinoma was associated with the parameters of lymphogenous metastasis.

The processes of vital activity of cancer cells mainly depend on the production of growth factors and their receptors. The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. Normally, binding of EGFR ligands and transforming growth factor alpha (TGFα) induces receptor activation, which triggers erk and PI3K signaling pathways that control cell proliferation, migration, invasion and many other processes. A number of studies have shown that a high percentage of EGFR expression is observed in 25–82 % of cases with rectal cancer. Thus, the expression and mutation of the EGFR gene is associated with various variants of tumor progression and an unfavorable prognosis for malignant tumors of various localizations. The purpose of the study was to investigate the EGFR expression in cancer tissue and evaluate the relationship between EGFR expression and parameters of lymphogenous metastasis in patients with rectal cancer. Material And Methods. Surgical specimens of 149 patients with stage T1–4N0–2M0, rectal adenocarcinoma, who were treated at the Cancer Research Institute of Tomsk National Research Medical Center, were studied using histological and immunohistochemical analyses. Positive EGFR expression was found in 88 (59.1 %) patients. Diagnosis was made according to WHO classification (2010). Results. When studying the EGFR expression in tumor cells on different depth of invasion, it was found that the positive expression of this marker was observed in cases with and without lymph node metastases. The analysis of the EGFR expression in various structures of the parenchymatous component of the tumor located in different layers of the intestinal wall showed that in the solid structures of the mucosa, the positive expression of EGFR was detected more often in cases without lymph node metastases. In patients with lymph node metastases, the percentage of the EGFR expression was lower. A similar pattern was observed in discrete groups of tumor cells. Conclusion. The study showed the presence of heterogeneity of the expression characteristics of the epidermal growth factor in various tumor structures located at different depths of infestation. The relationship between the parameters of lymphogenous metastasis and the positive EGFR expression indicates the prognostic significance of this marker.

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.

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.

Аim.The incidence of cardioesophageal cancer has been steadily increasing over the past few decades, posing significant diagnostic challenges.Materials and metods. X-ray examination remains the primary imaging modality for the initial diagnosis of gastric tumors. However, the modern imaging techniques, such as ultrasound (US) and spiral computed tomography (SCT) are needed to assess the extent of tumor invasion into the gastric wall and adjacent organs as well as lymph node involvement and metastatic spread.Conclusion.The role of US and SCT in diagnostic imaging of cardioesophageal cancer was studied and the examination algorithm using US and SCT with conventional X-rays was offered.

Introduction. The prognosis for surgical treatment of locally advanced gastric cancer remains disappointing. Neoadjuvant chemo-radiation therapy is relatively new and the least researched method of treatment, it is attracting more and more attention, mainly abroad in recent years. The aims of neoadjuvant therapy is the earliest start of systemic therapy, damage of the primary tumor and regional metastases, an increase in the percentage of radical operations, improving treatment outcome. Material and methods. The planning study is a multicenter, randomized clinical phase II trial. Patients of the first (experimental) group will be treated as the followes: neoadjuvant chemo-radiotherapy (total tumor dose of 46 Gy in 23 fractions with the concurrent modified CapOX scheme) followed by D2 gastrectomy and adjuvant chemotherapy. Patients of the second (control) group will be treated with D2 gastrectomy and adjuvant chemotherapy. Adjuvant chemotherapy will be carried out under the following schemes (optional for the researchers): CapOX or FOLFOX. Toxicity evaluation of neoadjuvant chemo-radiotherapy and adjuvant chemotherapy will be conducted with NCI CTC Toxicity Scale Version 3.0. The main objectives of the trial are to assess the safety and immediate effectiveness of neoadjuvant chemo-radiotherapy according to the criteria of the frequency and severity of postoperative complications and mortality, and tumor response. We are planning to include 80 patients with morphologically confirmed gastric cancer сT2–4N1–3, сT3–4N0–3; М0. The proposed trial will be carried out in accordance with the principles of the Helsinki Declaration, it has been approved by local ethic committees of the participated institutions. Results. As a result of this multicenter randomized trial it is planned to show the reproducibility of obtained in MRRC and a number of foreign centers results – that is, the safety and high immediate effectiveness of neoadjuvant chemo-radiotherapy in patients with locally advanced gastric cancer. Conclusion. If we reach the goals of the planning trial, the results would allow to reasonably recommend the start of large international phase III trials for the final evaluation of the proposed neoadjuvant treatment as a standard one in patients with locally advanced gastric cancer.

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.

During the period 2008–2011, esophageal cancer comprised 2,5 ± 0,2 % of all cases for males and 0,5 ± 0,1 % for females. Despite worldwide tendency towards decreased incidence of esophageal cancer, the rise in the age-standardized incidence rate was observed for both males and females of Tomsk region from 2000 to 2011. For males, the increase in both crude and age-standardized rates was registered. For females, the same tendency was observed in patients in the 50 to 64 age group.

A case of differential diagnosis of implantation metastasis in anterior abdominal wall following treatment for rectal cancer with the use of high-field MRI has been presented.

Short-and long-term surgical treatment outcomes of 15 patients with non-organic retroperitoneal tumors were presented. Surgical removal of the tumor was performed in 10 (66.7%) patients and combined resection of adjacent organs in 5 (33.3%) patients. The curative resection rate was 100%. Postoperative complications were observed in 2 (13.3±8.7%) patients. No postoperative lethality was registered. Local recurrence was diagnosed in 4 (26.7±11.4%) patients, of them 2 (13.3±8.7%) died of disease progression. Thus, in spite of certain difficulties associated with the need to perform traumatic surgeries, surgery remains the most effective treatment for non-organic retroperitoneal cancer.

Short-and long-term results of combined modality treatment including neoadjuvant chemotherapy were analyzed in patients with stage II-III esophageal cancer. Group I patients (n=18) received 2 courses of combined gemzar/cisplatin chemotherapy followed by radical surgery. The control group patients (n=20) underwent surgery alone. In the adjuvant chemotherapy group, the rate of immediate response was 38.9 % and complete response was observed in 1 (5.6 %) patient. Treatment was well tolerated by patients. The rates of postoperative complications did not significantly differ between the groups (22.2 % and 25.0 %, respectively, p>0.05). Combined modality treatment including neoadjuvant chemotherapy provided better 2-year overall and relapse-free survival rates than surgery alone (87.5 ± 8.2 % and 87.5 ± 8.2 % compared to 63.2 ± 11.1 % and 47.4 ± 11.4 %, respectively, р

The comparative analysis of the efficacy of anesthetic management in 53 patients with operable rectal cancer was carried out. In the study group patients (n=29), preemptive thoracic epidural analgesia was used. In the control group, (n=24), anesthesia was induced with sevofluorane and fentanyl. Preemptive thoracic epidural analgesia provided a reliable blockade of nociceptors and neural pathways, normalized stress response and decreased the severity of the systemic inflammatory response by stimulating the production of antiinflammatory cytokines.

The paper presents the analysis of the frequency of synchronous gastric and esophageal carcinomas in 176 patients with primary respiratory tract cancer, 122 (69.3%) of them with head and neck cancer and 54 (30.7%) with lung cancer. The endoscopic examination revealed synchronous gastric cancer (n=4) and synchronous esophageal cancer (n=1) in 5 (2.8 %) cases (3 with primary lung cancer and 2 with primary laryngeal cancer). These patients received anticancer treatment for synchronous polyneoplasias. Ninety-one (51.7 %) patients had gastric mucosal atrophy, which in 25.7 % of cases was characterized as premalignant lesions: grade I-II dysplasia (20.2%) and grade III dysplasia (5.5%). Considering the data obtained, patients with respiratory tract cancer have an increased risk for developing gastric and esophageal cancer. Endoscopic esophageal and gastric examination using advanced technologies should be included in the algorithm of management of these patients.

The literature review examines the main pathological and morphogenetic aspects of the development of peritoneal carcinomatosis and its molecular and biological features. In addition, the basic principles of peritoneal carcinomatosis classification have been presented and groups of tumors, which may be complicated by dissemination to the peritoneum, have been designated. Particular attention is paid to the problems of diagnosis and treatment.

The review presents data on the ubiquitin-proteasome system participation in pathogenesis of gastric cancer. The role of proteasome system in regulation of cell cycle, angiogenesis and tumor metastasis has been shown. The aspects of the participation of ubiquitin-proteasome proteolytic system in the pathogenesis of intensive muscle protein degradation in cancer cachexia are analyzed. The role of proteasome system in the development of H. Pylori-induced gastric cancer is discussed. The clinical assessment of selective proteasome inhibitor (bortezomib) is a promising area of research for metastatic gastric cancer.

Gastric cancer remains the most common cancer both worldwide and in the Russian Federation. Gastric cancer is the 3-rd most common cancer in men, comprising 9,1 % of all cancer cases and the 4-th most common cancer in women comprising 5,8 % of all cancer cases in Tomsk region in 2011. From 2000 to 2011, the crude and age-standardized gastric cancer incidence rates decreased by 13,4 % and 25,7 %, respectively in males and increased by 22,6 % and 11,1 %, respectively in females. In addition, the increase in gastric cancer incidence rate was observed in both male and female elderly population of Tomsk region.

Purpose: to study serum adipokine levels and AdipoR1, AdipoR2 and sOb-R expressions with respect to clinical-morphological parameters and the evidence of metaboloc syndrome (MS) in patients with stage I–III colon cancer.Materials and methods. The study included 31 colon cancer patients having metabolic syndrome and patients having no metabolic syndrome. Serum levels of leptin, adiponektin, AdipoR1, AdipoR2 and soluble form of the leptin receptor was assessed by ELISA.Results and conclusion. The incidence of MS in colon cancer patients was 71 %. The relationship between the serum leptin level and gender and disease stage was revealed. The tendency toward increase in the leptin level in patients with MS was shown. The Ob-R level was higher in patients having no MS. The levels of AdipoR1 and AdipoR2 were significantly higher in female colon cancer patients. Adiponectin receptors tended to increase in colon cancer patients with MS.