[D2 and D3 lymph node dissection for colon cancer]. / Rezul'taty limfodissektsii d2 i d3 pri rake obodochnoi kishki.

OBJECTIVE: To evaluate surgical and oncological results of standard and extended lymph node dissection (D2 and D3) in patients with colon cancer. MATERIAL AND METHODS: We analyzed treatment outcomes in 74 patients with colon cancer stage T1-4aN0-2M0 who underwent right- and left-sided hemicolectomy, resection of sigmoid colon with standard and extended lymph node dissection (D2 and D3). RESULTS: Surgical approach and level of D3 lymph node dissection did not increase intra- and postoperative morbidity. Laparoscopic interventions were followed by significantly lower intraoperative blood loss and earlier gas discharge. Metastatic lesion of apical lymph nodes was observed in 5 out of 36 patients who underwent D3 lymph node dissection (13.8%), and metastases in regional lymph nodes rN1-2 were found in all these patients. Overall 5-year survival was 86%. Disease-free and overall 5-year survival were similar after D2 and D3 lymph node dissection. CONCLUSION: D3 lymph node dissection is safe for colon cancer. Metastatic lesions of apical lymph nodes during D3 lymph node dissection were detected only in patients with lesions of regional lymph nodes (rN1-2). Disease-free and overall 5-year survival were similar after D2 and D3 lymph node dissection.

[Strangulated postoperative diaphragmatic hernia]. / Redkoe nablyudenie ushchemlennoi posleoperatsionnoi diafragmal'noi gryzhi.

We present a rare case of postoperative diaphragmatic hernia in a patient with colon infringement 3 years after surgery for cardioesophageal cancer accompanied by extensive diaphragmotomy. The diagnosis of diaphragmatic hernia with colon infringement was based on a combination of anamnestic, clinical and radiological data, as well as results of diagnostic pleural puncture. This clinical case is of interest due to small incidence of disease and difficult interpretation of clinical and diagnostic data.

[Results of redo liver resections for metastatic colorectal cancer]. / Rezul'taty povtornykh rezektsii pecheni pri metastaticheskom kolorektal'nom rake.

OBJECTIVE: To analyze patients undergoing redo liver resections for metastatic colorectal cancer. MATERIAL AND METHODS: The study included 14 patients with colorectal cancer who underwent several redo liver resections for metastatic lesions between September 2011 and June 2021. Mean age of patients was 63.5 years. Left-sided colonic G2 adenocarcinoma T4N1-2 prevailed (wild-type KRAS). RESULTS: Fourteen patients (100%) underwent two liver resections, 7 (50%) - three resections, 1 (7.1%) - four resections. Mean period between the first and the second liver resections was 16.2 months, between the second and the third resections - 9.9 months, between the third and the fourth resections - 5 months. Maximum follow-up period after primary surgery was 9 years and 9 months. Seventy-five percent of patients were alive after 34.2 months, 50% - after 58.9 months. N+ status of colorectal tumor decreased survival while KRAS mutation and synchronous metastatic liver lesions increased survival. CONCLUSION: Redo liver resections for metastatic colorectal cancer are safe and ensure favorable long-term survival in certain patients.

Regulatory network of competitively interacting RNAs and effectiveness of rectal tumors radiotherapy.

BACKGROUND: Currently, rectal tumors radiotherapy effectiveness reaches an acceptable level only in a small number of patients (they have a complete clinical response), which is associated with the formation of malignant cells radioresistance. A comprehensive study that integrates various epigenetic parameters would explain a number of molecular mechanisms of rectal tumor cells radioresistance and identify new bio-markers. In the last decade, using high-through-put sequencing, the competitively interacting RNAs regulatory network (long non-coding RNAs, miRNAs and mRNAs) has been shown. PURPOSE: The aim of the study was to analyze the features of competitively interacting RNAs regulatory network functioning in patients with rectal cancer who are radioresistant and sensitive to radiotherapy. The study was performed on 500 patients with dia-gnosed rectal cancer. Radiotherapy was performed on a Novalis TX linear particle accelerator according to the standard protocol (single focal dose 2.4 Gy, total focal dose 54.0 Gy). Total RNA preparations were isolated from paired bio-psy fragments of tumor and non-tumor tissues of the rectum (obtained by video-colonoscopy). The relative abundance of mRNA, miRNA and lncRNA transcripts was assessed by the RT-qPCR method. Using bio-informatic analysis, the probability of potential interactions between the investigated mRNA, miRNA and lncRNA was determined. It has been shown that the effectiveness of radiotherapy depends on the level of miRNA (miRNA-195-5p; miRNA-4257; miRNA-5187-5p; miRNA-149-5p; miRNA-138 -1-3p; miRNA-6798-5p; miRNA-6819-5p; miRNA-4728-5p; miRNA-1249-5p; miRNA-557; miRNA-1273h-5p; miRNA-6737-5p; miRNA-6808-5p; miRNA-3202; miRNA-5195-3p; miRNA-130b-3p) and lncRNA (XIST, HELLPAR, NEAT1, AC008124. 1, LINC01089, LINC01547, and VASH1-AS1) expression, which regulate the DNA repair system (H2AX, RBBP8) and apoptosis (BCL2). CONCLUSION: A comprehensive study of competitively interacting RNAs regulatory network and radiotherapy effectiveness of rectal tumors made it possible to establish the mechanisms of radioresistance formation and its bio-markers.

[Gastrointestinal stromal tumors: potential of minimally invasive surgical interventions]. / Gastrointestinal'nye stromal'nye opukholi: vozmozhnosti maloinvazivnykh operativnykh vmeshatel'stv.

OBJECTIVE: To analyze the issue of gastrointestinal stromal tumors (GISTs) and potential of minimally invasive surgical interventions. MATERIAL AND METHODS: We analyzed postoperative outcomes in 97 patients with gastric and intestinal GISTs who underwent surgical treatment at the National Medical Research Centre for Oncology between 2015 and 2020. RESULTS: Twenty (24.7) patients with gastric GISTs underwent laparoscopic partial and distal gastric resections. Five (35.7%) patients with GISTs of the small intestine underwent minimally invasive segmental bowel resections. Only minimally invasive interventions were performed in patients with rectal GISTs. Analysis of laparoscopic and open surgeries for GISTs found no significant differences. Analysis of laparoscopic and open surgeries for gastric and small bowel GISTs revealed the obvious advantages of minimally invasive access regarding postoperative outcomes. Indeed, we found no need for nasogastric drainage in 50% of patients (p<0.001), earlier recovery of intestinal motility and oral feeding (p<0.001), lower postoperative morbidity (p=0.036), fast recovery of motor activity (p<0.001) and shorter postoperative hospital-stay (p<0.001). CONCLUSION: Despite small incidence, GISTs are a complex problem in modern oncology. Diagnosis and treatment require a multidisciplinary medical team (morphologists, geneticists, radiologists, surgeons, chemotherapists, gastroenterologists and other specialists) that is possible in a reference center. Minimally invasive interventions for GISTs of the stomach, small intestine and rectum improve postoperative course.

[Esophageal squamous cell carcinoma localized in pharyngeal-esophageal diverticulum]. / Redkii sluchai ploskokletochnogo raka pishchevoda s lokalizatsiei v glotochno-pishchevodnom divertikule.

Squamous cell carcinoma in Zenker's diverticulum was first described in 1933. No large studies have yet been conducted due to rarity of this disease. There are a lot of unresolved issues regarding diagnosis and treatment of this pathology. In the literature, there are only few reports on cancer of Zenker diverticulum. It is only known that clinical symptoms are not specific, and diagnosis of carcinoma is traditionally correlated with age and male sex. Despite esophageal localization of primary tumor, its development can take up to 10 years. The authors report squamous cell carcinoma in Zenker diverticulum, discuss the main difficulties of morphological verification of this disease and choice of surgical approach.

[Surgical treatment of bilateral metachronous primary multiple non-small cell lung cancer using extracorporeal membrane oxygenation]. / Khirurgicheskoe lechenie bilateral'nogo metakhronnogo pervichno-mnozhestvennogo nemelkokletochnogo raka legkogo s ispol'zovaniem ekstrakorporal'noi membrannoi oksigenatsii.

Lung surgeries following pneumonectomy using veno-venous extracorporeal membrane oxygenation (V-V ECMO) are described in the literature. The authors report a 62-year-old man with bilateral metachronous primary multiple lung cancer after previous extended lower lobectomy combined with sublobar resection of the upper lobe for squamous cell carcinoma of the left lung. Despite satisfactory functional status and heart function, the patient had poor lung function. Therefore, we decided to increase safety of resection using extracorporeal respiratory support. Extended right lower lobectomy was carried out under V-V ECMO. Surgery was followed by intrapleural bleeding that required urgent surgical hemostasis with completion of perioperative V-V ECMO. Postoperative ventilation lasted for 33 days but the patient was discharged later in a satisfactory condition.

[Сurrent views on predictors and biomarkers of early diagnosis of anthracycline-mediated cardiotoxicity in patients with breast cancer (review of literature).]

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2ß, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors.

Copy Number Variation in Tumor Cells and Extracellular DNA in Patients with Lung Adenocarcinoma.

Copy number variation of some gene loci in lung tumor cells extracted by laser capture microdissection and in cell-free DNA in the plasma of patients with lung cancer was analyzed for identification of potential molecular markers. Tissue specimens fixed in formalin and embedded in paraffin blocks (FFPE-blocks) from 90 patients and extracellular DNA from plasma samples of 70 patients and 30 donors were used. Copy number variation was assayed for 30 genes (BAX, BCL2, C-FLAR, P53, MDM2, CASP9, CASP3, CASP8, SOX2, OCT4, PIK3, MKI67, HV2, HIF1A1, XRCC1, MMP1, TERT, CTNNB1, KRAS, EGFR, GRB2, SOS1, MAPK1, STAT1, BRAF, FTO, and mir3678) and reference loci (ACTB, B2M, and GAPDH) by the real-time quantitative PCR. Changed copy numbers were detected for genes responsible for apoptosis regulation (BAX, P53, and CASP3), proliferation (SOX2), DNA reparation (XRCC1), oxidative phosphorylation (HV2), EGFR signaling pathway (GRB2, SOS1, MAPK1, STAT1, and BRAF), and for mir3678 gene in lung tumor cells and extracellular DNA.

[Short-term outcomes of surgical treatment of gastroesophageal junction cancer]. / Neposredstvennye rezul'taty khirurgicheskogo lecheniia kardioézofageal'nogo raka.

OBJECTIVE: To confirm simplicity, safety and efficacy of stapling devices for gastroesophageal anastomosis (including those formed in mediastinum) in the treatment of gastroesophageal junction cancer. MATERIAL AND METHODS: There were 147 patients with cardioesophageal cancer. Tumors Siewert type II and III were predominant (44.2 and 40.3%, respectively). Simultaneous procedures were performed in 30.6% of cases. RESULTS: Postoperative complication rate was 42.2%. Pneumonia was the most common. Postoperative mortality was 2.7%.

[Conversion of laparoscopic access in colorectal cancer surgery (in Russian only)]. / Konversiia laparoskopicheskogo dostupa v khirurgii kolorektal'nogo raka.

AIM: To analyze the problem of access conversion in laparoscopic surgery for colorectal cancer. MATERIAL AND METHODS: There were 876 procedures for colorectal cancer T14N01M0 performed at the Rostov Research Institute of Oncology in 2015-2017. Open and laparoscopic surgery was applied in 562 and 309 patients, respectively. Conversion of laparoscopic procedures was required in 35 (10.2%) patients. RESULTS: Conversions were 2.7 times more frequent in men (p<0.05) (probably due to anatomical features - a narrow pelvis) and predominantly with rectosigmoid (22.2%, 2 patients) and rectal cancer (12%, 22 patients). Conversions in women were as well in right-sided colon cancer (9.7%, 3 cases) and sigmoid cancer (7.4%, 4 patients). Conversions were performed mostly due to locally advanced tumors (37.1%, 13 patients) which are especially baffling in case of narrow pelvis. Visceral obesity (20%, 7 patients) and abdominal adhesions (17.1%, 6 patients) were also important causes of conversions. Conversions did not affect time of surgery (256 min vs. 240 min in laparoscopic and 237 min in open surgery). Intraoperative blood loss (284 ml) was higher than in laparoscopy (240 ml) but did not exceed that in open surgery (291 ml). CONCLUSION: It is necessary to assess risks and benefits of laparoscopy in patients with high probability of conversion in colorectal cancer surgery.

Specific Features of Transcription Activity of Cancer-Testis Antigens in Patients with Metastatic and Non-Metastatic Breast Cancer.

Cancer-testis antigens, effective markers of tissue malignant transformation, are characterized by heterogonous transcription depending on the pathological features of breast cancer. We performed screening of transcription profile of cancer-testis antigens specific for breast tumor tissues in female patients with and without regional metastasis. The relative expression of 16 genes (MAGEA1, MAGEA2, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, GAGE4, MAGEC1, BAGE, XAGE3, NY-ESO1, SSX2, SYCP1, and PRAME1) was analyzed by RT-qPCR method in biopsy specimens of the mammary gland tissues obtained during surgery from 25 patients. Differential transcription activity of cancer-testis antigens genes was observed in patients with metastatic (enhanced expression of MAGEA2, MAGEB1, and XAGE3 genes) and non-metastatic (enhanced expression of GAGE3 and PRAME1 genes) breast cancer.

Familial adenomatosis of the colon: current state of the problem.

AIM: The urgency of the problem of familial adenomatosis of the colon (FAC) is caused both by the severity of the disease with the inevitable development of cancer without timely treatment, and the involvement of the patient's blood relatives in this problem. Due to the rare inci- dence of this disease, many issues require discussion. To determine the possibility of timely treatment of FAC patients maintaining a satisfactory quality of life. MATERIALS AND METHODS: The data on 5 FAC patients and 12 their blood relatives were studied. Clinical, endoscopic and genetic characteristics of the disease and treatment were analyzed. Results. Demonstrated that family history, genetic and endoscopic examinations allow diagnosis of FAC. Colectomy with rectal resection and the creation of a small intestine reservoir with reservoir-rectal anastomosis provide a sufficient quality of life for patients. Examination of the patient's blood relatives reveals new patients requiring additional examination and treatment. CONCLUSION: The problem of FAC is multidisciplinary and involves therapists, gastroenterologists, pediatricians, geneticists, endoscopists, radi- ologists, surgeons and oncologists. Only a timely diagnosis can help the patient to undergo radical treatment before the development of colon cancer.

[The role of micro-RNA in the regulation of signal pathways in gliomas]. / Rol' mikro-RNK v reguliatsii signal'nykh putei pri gliomakh.

Gliomas are invasive brain tumors with high rates of recurrence and mortality. Glioblastoma multiforme (GBM) is the most deadly form of glioma with nearly 100% rate of recurrence and unfavorable prognosis in patients. Micro-RNAs (miR) are the class of wide-spread short non-coding RNAs that inhibit translation via binding to the mRNA of target genes. The aim of the present review is to analyze recent studies and experimental results concerning aberrant expression profiles of miR, which target components of the signaling pathways Hedgehog, Notch, Wnt, EGFR, TGFb, HIF1a in glioma/glioblastoma. Particularly, the interactions of miR with targets of 2-hydroxyglutarate (the product of mutant isocytrate dehydrogenase, R132H IDH1, which is specific for the glioma pathogenesis) have been considered in the present review. Detecting specific miRNAs in tissue and serum may serve as a diagnostic and prognostic tool for glioma, as well as for predicting treatment response of an individual patient, and potentially serving as a mechanism for creating personalized treatment strategies.

Modeling of Lymphogenous and Hematogenous Metastasizing from Murine В16 Melanoma in Rats.

We developed a model of experimental melanoma. Intralienal xenogeneic transplantation of a suspension of melanoma cells B16 in physiological saline (0.1 ml; 1:10) was conducted to outbred male rats. In 6 months, histologically confirmed melanoma B16 in the spleen and its metastases in the liver, intestine, pancreas, adrenal glands, and lungs (hematogenous metastasis), as well as in the thymus and lymph nodes (lymphogenous metastasis) were revealed in rats. The proposed rat model of melanoma B16 metastasizes by the hematogenous and lymphogenous pathways, develops over 6 months, and allows receiving sufficient volume of material for analysis.

[The activity of proapoptotic genes increases after renal ischemia/reperfusion].

According to the World Health Organization, pathologies associated with ischemia/reperfusion occupy the leading position in the structure of mortality. The efficiency of localized kidney cancer surgery is limited by the damaging effects of prolonged warm ischemia and reperfusion. Ischemia/reperfusion damage to renal tissue may be related to changes in the expression profiles of pro- and antiapoptotic genes. Here, we have presented the longitudinal expression profiles of apoptosis-related genes in tissues of left and right (intact) kidneys of male rats exposed to unilateral ischemia followed by reperfusion. The profiles have been assessed at time points of 1, 3, and 48 h after the ischemic/reperfusion exposure by RT-qPCR quantification of mRNAs encoded by 13 genes, including BAX, p53, AIFM1, APAF1, CASP8, CASP3, CASP9,CASP7, MDM2, BCL2, CIAP1, XIAP, and ICAD, after normalization with respect to a reference gene ACTB. The study revealed a shift in the expression of pro- and antiapoptotic genes toward the predominance of proapoptotic processes, as was evinced by the increase in expression detected for the BAX, p53, AIFM1, APAF1, and CASP8 genes. One hour after the reperfusion, activation of mitochondrial, or intrinsic apoptosis was detected, while р53-dependent and extrinsic, i.e., receptor-driven, apoptosis joined at later time points. Changes in the level of expression of caspase 7 (CASP7)-encoding mRNA have only been detected 48 h after the restoration of blood flow. Changes have been observed in the transcription of pro- and antiapoptotic genes in tissues of both kidneys, which suggests the involvement of the contralateral kidney in systemic pathological process that develops during unilateral ischemia/reperfusion.

[A plasminogen regulation system in brain tumors]. / Sistema reguliatsii plazminogena v razlichnykh opukholiakh golovnogo mozga.

INTRODUCTION: Tumor progression and neovascularization during malignant processes are believed to be associated with plasminogen activators and the PAI-1 inhibitor, but their role and interactions in various types of brain tumors have been studied insufficiently. AIM: To conduct a comparative study of plasminogen regulation in optic nerve sheath meningiomas, glioblastomas, and brain metastases of breast cancer, as well as in perifocal tissues surrounding the tumors. MATERIAL AND METHODS: Tumors and perifocal areas of 19 breast cancer (BC) metastases, 24 glioblastomas, and 13 meningiomas without perifocal edema were investigated by ELISA in 56 patients aged 35-72 years. Histological control was carried out in each case. RESULTS: Significant differences were found in the levels of urokinase (uPA), tissue plasminogen activator (tPA), and PAI-1 inhibitor between glioblastomas and breast cancer metastases and the histologically unaltered (relatively intact) tissue around meningioma lesions (p≤0.05 in all cases). The levels of uPA-AG and uPA-act in meningioma were higher than those in the relatively intact tissue, while the levels of both tPA forms were reduced. The levels of uPA-AG and uPA-act in both malignant tumors and their perifocal areas were elevated compared to those in the relatively intact tissue. The levels of both tPA forms were reduced in all other tissues, except for glioblastoma. The level of PAI-1 inhibitor in malignant tissues was higher (being predominant in tumors) compared to that in the intact tissue surrounding meningioma, as well as relative to that in meningioma. The study proves that uPA and its inhibitor PAI-1 are directly involved in the metabolism of malignant gliomas and brain metastases of breast cancer. The role of tPA is to protect meningiomas; tPA activation in malignant brain tumors is suppressed.

[CORRECTION ENERGY DEFICIENT STATES AS POSSIBLE PERIOPERATIVE ADAPTATION OF CANCER HEPATOPANCREATODUODENAL ZONE PATIENTS.]

The aim of this study was to determine the role remaxol in complex intensive therapy of various jorms gipoergosis dur- ing the perioperative period in patients with hepatopancreatoduodenal zone malignancies. The treatment of 48 patients was analyzed. Immediately prior to surgery, at random, patients were divided into primary (n = 26) and control group (n = 22). In the study group for compensation the energy deficient states and organ hypoxia in the pancreas and the liver during the intra- and postoperative periods remaxol was included in the infusion therapy, the introduction ofwhich had been began before the start of anesthesia. In the control group antihypoxants weren't used. Integral assessment of prognosis and severity on a scale SAPS II and APACHE II. Status of energy and the type of energy deficit was estimated by the transport of oxygen and the concentration of lactate. In order to determine the level of stress exposure and the for- mation of adaptive reactions examined quantitative and qualitative composition of the peripheral blood. The study was conducted prior to surgery, on the 2nd and 5th day perioperative period. Inclusion in the scheme of metabolic remaxol program in the perioperative period in patients with malignant diseases of hepatopancreatoduodenal zone promotes the reduction of different types ofgipoergosis, efficient delivery and oxygen consumption, the adequacy of tissue oxygenation and restoration of adaptive physiological reactions such as.

[Combined surgery for locally advanced colorectal cancer]. / Kombinirovannye operativnye vmeshatel'stva pri mestno-rasprostranennom kolorektal'nom rake.

AIM: To study the types and early outcomes of combined interventions for locally advanced colorectal cancer. MATERIAL AND METHODS: Since 2009 four hundreds and ninety eight patients underwent surgery in the Rostov Research Institute of Oncology for locally advanced colorectal cancer. Most cases of surgical procedures on adjacent organs included resection of small intestine (23.69%), supravaginal hysterectomy (16.47%), resection of bladder (12.25%), total hysterectomy (11.45%). RESULTS: Postoperative complications occurred in 178 (35.7%) patients. Their incidence was significantly lower in case of laparoscopic approach (12.5%). Functional-sparing interventions on bladder followed by its augmentation with enteric graft improves rehabilitation. CONCLUSION: Laparoscopic approach and functional-sparing surgery improve the results of locally advanced colorectal cancer management.

[Epigenetic markers of esophageal cancer: DNA methylation]. / Épigeneticheskie markery malignizatsii tkanei pishchevoda: metilirovanie DNK.

Adenocarcinoma and squamous cell carcinoma are the most common types of esophageal cancer with a constant tendency to increase the incidence of growth on the background of the high mortality, which makes particularly the development of new biomarkers that complement and improve the early diagnosis of this disease. Despite the impressive number of studies in routine clinical practice is used only marker of esophageal cancer - ERBB2/HER2 status. This review summarizes data on the identified epigenetic markers of the aberrant methylation of the genome, which may be useful for early detection of esophageal cancer, prognosis estimation and / or prediction of response to treatment. The development of new high-tech genome-wide screening, such as beadarray and immunoprecipitation sequencing method used for the wideband genotyping, but for the analysis of transcriptome and metilom, provides a comprehensive picture of genetic and epigenetic changes during tumorigenesis. Note the need to verify the most biomarkers on large representative samples for the development of valid diagnostic panels, suitable for large-scale screening of risk groups.