Tomsk National Research Medical Center Research Articles

Successful surgical treatment of metachronous carcinoma of the appulla of Vater and ductal carcinoma of the distal parts of the pancreas

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

The <i>LGALS1</i> gene polymorphism is not associated with galectin-1 levels in tumor tissue and blood of colon cancer patients

Background: Galectin-1 plays an important role in the pathogenesis of colorectal cancer (CRC). The blood and tumoral levels of galectin-1 could be dependent on the polymorphism of the promotor region of LGALS1 gene. Aim: To analyze an association between galectin-1 levels in tumor tissue and plasma and the genotype of the rs4820293 and rs4820294 polymorphisms of the LGALS1 gene in CRC patients. Materials and methods: The study included a total of 70 inpatients with pathologically verified CRC (International Classification of Diseases 10th Revision codes C18-C20, 39 men and 31 women, mean age 65.4 ± 5.7 years), who were receiving treatment in the Tomsk Regional Oncology Center and Cancer Research Institute of the Tomsk National Research Medical Center from 2020 to 2022. The control group consisted of 70 healthy volunteers (34 men and 36 women, mean age 62.3 ± 7.2 years). Venous blood samples were taken from all study participants and tumor tissue samples were obtained from the CRC patients. Galectin-1 expression in the tumor tissue was assessed by immunohistochemistry and plasma galectin-1 levels by enzyme-linked immunosorbent assay. The LGALS1 gene polymorphisms rs4820293 and rs4820294 were identified by restriction fragment length polymorphism analysis. Results: The distributions of genotype and allele frequencies of polymorphic variants rs4820293 and rs4820294 of the LGALS1 gene in the CRC patients and in the healthy donors were comparable (p 0.05). Calculation of odds ratios did not confirm any association between LGALS1 gene polymorphisms and CRC. However, the rs4820294 polymorphism had a strong association with regional metastasis and tumor differentiation grade (Cramer's V above 0.4, p 0.001). The plasma galectin-1 levels in the CRC patients with the AA genotype of the rs4820294 polymorphism were higher than in the healthy carriers (17.42 versus 12.92 ng/ml, p = 0.040). However, there were no significant differences in the content of galectin-1+ cells in the tumor and galectin-1 in plasma of the CRC patients depending on the genotype of the LGALS1 gene polymorphisms (p 0.05). Conclusion: The LGALS1 gene polymorphism is not associated with CRC, but in the carriers of the rs4820294 variant is related to clinical and morphological parameters of the tumor process. The intratumoral expression and blood levels of galectin-1 in CRC patients are not dependent on the genotype of rs4820293 and rs4820294 polymorphisms of the LGALS1 gene.

Low expression of the <i>ST6GAL2</i> and <i>CD248</i> genes as an unfavorable prognostic marker of oral squamous cell carcinoma

Introduction. Squamous cell carcinoma (SCC) of the oral cavity is an aggressive and rapidly progressing disease. The tendency to progression of the tumor process is due to the clinical and pathological characteristics of the patient and the biological characteristics of the tumor. molecular and genetic disorders related with transcriptome level play an important role in tumor progression, which can be used in predicting the outcome of the disease. Aim. To identify markers for assessing the risk of the SCC progression. Materials and methods. Based on the data of the Cancer genome Atlas database, a bioinformatic search for genes associated with the progression of SCC was performed (11 genes were selected). Then we performed a retrospective analysis of clinical data and histological material from 38 patients with SCC treated at the Scientific Research Institute of Oncology of the Tomsk National Research medical Center of the Russian Academy of Sciences from 2018 to 2021. Fixed samples of tumor tissue were examined. The level of gene expression was determined by real-time quantitative polymerase chain reaction. Results. It was shown that decrease in the ST6GAL2 matrix RNA level is associated with presence of lymphogenic metastases and decrease in the CD248 matrix RNA level is associated with the occurrence of relapses. Conclusion. Expression level of the ST6GAL2 and CD248 genes can be used as predictors of an unfavorable prognosis of SCC.

Transcriptional, growth factors, components of the AKT/mTOR signaling pathway, receptors and ligands of programmed cell death expression in melanoma

Introduction. Melanoma is the most dangerous neoplasm of the skin, characterized by a malignant and aggressive course. Transcriptional and growth factors, components of the AKT/mTOR signaling pathway, receptors and ligands of programmed cell death are involved in significant processes of oncogenesis.Aim. To study the expression of components of the AKT/mTOR (mTOR – mammalian target of rapamycin) signaling pathway, transcription and growth factors, expression of AMPK, LC3B, programmed cell death 1 (PD-1), programmed death-ligand 1 PD-L1 and programmed death-ligand 2 (PD-L2) in skin and mucosal tumor tissues.Materials and methods. The study included 21 patients with a verified diagnosis of melanoma of the skin of various localizations and mucous membranes of the nasal cavity T1a–4bN0M0 (I–IV stages) and 18 patients with basal cell carcinoma of the skin of various localizations T1–4N0M0 (I–VIA stages), aged 45 to 72 years old, who were treated in the department of head and neck tumors of the Cancer Research Institute, Tomsk National Research Medical Center. The presence of tumor ulceration was determined by microscopy and registration of the true absence of the epidermis over the tumor or due to traumatization of the epidermis. Expression of components of the AKT/mTOR signaling pathway, transcription and growth factors, expression of AMPK, LC3B, PD-1, PD-L1 and PD-L2 in the tumor tissue was determined by real-time polymerase chain reaction.Results. An increase in the expression of 70 S6 kinase and VHL was found in melanoma tissues compared to basal cell carcinoma. At the same time, the presence of signs of ulceration was associated with a low level of c-RAF, nuclear factor kappa B (NF-kB) p50 and hypoxia-inducible factor 1 (HIF-1) matrix RNA (mRNA) against the background of an increase in the expression of the hypoxia-inducible factor 2 (HIF-2) transcription factor. The study of the molecular features of neoplasms in relation to the tumor thickness according to Breslow revealed the contribution of transcription and growth factors, the intensity of intracellular signaling processes, modification of the microenvironment, autophagy and neoangiogenesis.Conclusion. The molecular and biological features of melanomas associated with invasive tumor growth have been identified. An increase in the expression of 70 S6 kinase and VHL are characteristic of a malignant skin tumor. The presence of signs of ulceration and tumor invasion were associated with a change in the transcriptional characteristics of factors with the induction of key markers, oncogenesis, which contributes to the formation of the invasive potential of the tumor.

The 45th anniversary of Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences

Решение об открытии в Томске филиала Онкологического научного центра Академии медицинских наук СССР было принято 3 января 1979 г. Государственным комитетом СССР по науке и технике, а уже 8 января 1979 г. министром здравоохранения СССР академиком АМН СССР Б.В. Петровским был подписан Приказ № 20 «Об организации в г. Томске Сибирского филиала Онкологического научного центра АМН СССР».

Clinicopathological features of colon cancer depending on the dMMR status of the tumor

Aim. To conduct a clinical and morphological assessment of the characteristics of colon cancer depending on the dMMR / pMMR status of the tumor.Materials and methods. A retrospective study included 66 patients with operable colorectal cancer (CRC) (T1-4bN0-2bM1), who were treated at Cancer Research Institute of Tomsk National Research Medical Center (NRMC). The average age of the patients was 64.4 ± 12.8 years. All patients underwent hemicolectomy or colon resection, as well as intraoperative resection of distant metastases, if present.Results. We determined that in CRC patients with pMMR tumors, hematogenous metastases were detected in 27.3% of cases, while in patients with dMMR tumors, hematogenous metastases were detected only in 6.1% of cases (p = 0.021). A comparative analysis of dMMR and pMMR tumors also allowed to establish higher frequency of perineural invasion among the pMMR subgroup of carcinomas (p = 0.039). The sign of tumor budding was found both in dMMR carcinomas (36%) and in pMMR tumors (45%). This sign was associated with damage to regional lymph nodes (p = 0.0017). A more detailed analysis of the tumor budding phenomenon showed that in dMMR tumors, Bd1 low-grade budding (83%) predominated. In pMMR tumors, Bd2 intermediate-grade budding (33%) and Bd3 high-grade budding (26.7%) prevailed. Bd2 and Bd3 tumor budding types were associated with hematogenous metastasis (p < 0.001).Conclusion. The obtained data demonstrate the differences in such pathomorphological parameters as perineural invasion and the degree of tumor budding depending on the dMMR / pMMR status of the tumor. These histologic parameters in tumor tissue are also associated with higher incidence of distant metastasis in patients with pMMR carcinomas as opposed to patients with dMMR tumors.

SOME ASPECTS OF CORONARY ARTERY BYPASS GRAFTING IN MYOCARDIAL INFARCTION WITHOUT ST ELEVATION

HighlightsThe frequency of coronary artery bypass grafting in patients with non-ST-elevation myocardial infarction (NonSTEMI) in the Research Institute of Cardiology “Tomsk National Research Medical Center of the Russian Academy of Sciences” is equal to 10%, hospital mortality is 4.3%, which corresponds to the literature data. Patients with NonSTEMI who undergo coronary artery bypass grafting in cardiac surgery centers in Tomsk, Kemerovo and Chelyabinsk do not differ in main clinical and anamnestic characteristics. Patients with NonSTEMI who undergo CABG in cardiac surgery centers in Leipzig and Kiel (Germany), have a higher surgical risk compared with patients in Russian centers, while they are operated on much earlier than in Russian centers, and there are no statistically significant differences in hospital mortality between clinics. AbstractAim. To perform a comparative analysis of clinical and anamnestic characteristics and treatment outcomes in NonSTEMI patients who underwent CABG in 2020 at the Research Institute of Cardiology “Tomsk National Research Medical Center of the Russian Academy of Sciences” and in other domestic and foreign clinics.Methods. The retrospective study involved 23 NonSTEMI patients/ The patients clinical and anamnestic characteristics after CABG and the main outcome of treatment were analyzed. The obtained results were compared with the data of 4 other cardiac surgery clinics that were found in the literature.Results. The frequency of CABG in NonSTEMI patients is 10%, which corresponds to the literature data. The mean age of these patients was 64.8±8.4 years, LVEF – 55.5±9.2%, the risk according to the GRACE score – 4.9±5.6%, according to the EuroSCORE – 7.3±2.1%. There were no patients with cardiogenic shock or dialysis. The duration of hospitalization prior to surgery was 7.4±5.3 days. The hospital mortality was 4.3%. The clinical and anamnestic characteristics of NonSTEMI patients who underwent CABG surgery in the clinics of Tomsk, Kemerovo (n = 66), Chelyabinsk (n = 101), Leipzig (n = 758) and Kiel (n = 461) were compared. The characteristics of patients of the Russian clinics did not differ. It was found that in Russian clinics these patients were younger, and had less severe complications of the disease, and less severe comorbid diseases in comparison with patients of the German clinics. In particular, in the Russian clinics, CABG was not performed in patients with cardiogenic shock, unlike in the German clinics. At the same time, the German clinics conduct surgery on NonSTEMI patients much earlier than in the Russian clinics: only 10–20% of patients are operated on in the Russian clinics in the first 3 days of the disease, whereas in Leipzig – 42% of patients, and in Kiel almost all patients – on the first day of the disease; there were no statistically significant differences in hospital mortality between clinics.Conclusion. According to the results of the analysis, clinical and anamnestic characteristics of NonSTEMI patients who undergo CABG in Russian cardiac surgery centers (Tomsk, Kemerovo and Chelyabinsk) do not differ. Compared with the patients of the German cardiac surgery centers of Leipzig and Kiel, Russian patients have a lower surgical risk, they are operated on much later, there were no statistically significant differences in hospital mortality between clinics.

Factors Associated With Hospital Mortality in Acute Myocardial Infarction

Aim To determine clinical and laboratory parameters associated with in-hospital mortality in patients with acute myocardial infarction and to develop a multifactorial prognostic model of in-hospital mortality.Material and methods This was a study based on the 2019-2020 Registry of acute coronary syndrome of the Tyumen Cardiology Research Center, a branch of the Tomsk National Research Medical Center. The study included 477 patients with ST-segment elevation acute myocardial infarction (AMI), 617 patients with non-ST segment elevation AMI, and 26 patients with unspecified AMI. In-hospital mortality was 6.0 % (n=67). Clinical and laboratory parameters were assessed on the day of admission. The separation power of indicators associated with in-hospital mortality was determined using a ROC analysis. The data array of each quantitative parameter was converted into a binary variable according to the obtained cut-off thresholds, followed by creation of a multifactorial model for predicting in-hospital mortality using a stepwise analysis with backward inclusion (Wald). The null hypothesis was rejected at p<0.05.Results The multivariate model for prediction of in-hospital mortality included age (cut-off, 72 years), OR 3.0 (95 % CI: 1.5-5.6); modified shock index (cut-off threshold, 0.87), OR 1.5 (95 % CI: 1.1-2.0); creatine phosphokinase-MB (cut-off threshold, 32.8 U / L), OR 4.1 (95 % CI: 2.2-7.7); hemoglobin (121.5 g / l), OR 1.7 (95 % CI: 1.2-2.3); leukocytes (11.5×109 / l), OR 1.9 (95 % CI: 1.3-2.6); glomerular filtration rate (60.9 ml / min), OR 1.7 (95 % CI: 1.2-2.2); left ventricular ejection fraction (42.5 %), OR 4.1 (95 % CI: 2.0-8.3); and size of myocardial asynergy (32.5 %), OR 2.6 (95 % CI: 1.4-5.0).Conclusions Independent predictors of in-hospital mortality in AMI are age, modified shock index, creatine phosphokinase-MB, peripheral blood leukocyte count, hemoglobin concentration, left ventricular ejection fraction, size of myocardial asynergy, and glomerular filtration rate. The in-hospital mortality model had a high predictive potential: AUC 0.930 (95 % CI: 0.905-0.954; p <0.001) with a cutoff threshold of 0.15; sensitivity 0.851, and specificity 0.850.

Immunohistochemical subtyping and evaluation of the prognosis of basal-like triple-negative breast cancer based on IDO1 protein expression

Background. Known subtypes of triple-negative breast cancer, despite the common basal-like profile, have certain features that differ in terms of the course and prognosis of the disease. Therefore, the study of molecular markers that make it possible to identify subtypes of basal-like carcinomas and evaluate a probable prognosis based on their expression indicators is relevant today.
 Aim. Conduct immunohistochemical subtyping of basal-like triple-negative breast cancer based on the assessment of IDO1 protein expression, compare the obtained data with clinical and morphological characteristics, as well as indicators of tumor sensitivity to neoadjuvant therapy.
 Material and methods. The study was retrospective and included 42 patients diagnosed with triple negative breast cancer (mean age 50.512.7 years), disease stage T14dN03M0. The patients were treated in the Departments of Chemotherapy and General Oncology of the Research Institute of Oncology of the Tomsk National Research Medical Center from 2016 to 2021. A morphological study of tumor tissue samples, breast core biopsies, and surgical material was performed. Immunohistochemical study was carried out on sections of core biopsies. The expression of markers was evaluated, the obtained data were compared with clinical and morphological characteristics, as well as with indicators of tumor sensitivity to neoadjuvant therapy. Statistical analysis was carried out using the Statistica 10.0 program, data comparison was performed using the methods of descriptive statistics and nonparametric method of Pearson's 2 test.
 Results. The immunoactivated subtype was determined with the status of CK5/6+/IDO1+ carcinomas, such tumors were dominant and accounted for 81.25% (n=26/32). In these cases (CK5/6+/IDO1+), the presence of metastatic lesions in the axillary lymph nodes was statistically significantly less common, and the frequency of complete pathomorphological regression was higher than in carcinomas, the molecular profile of which corresponds to the immunosuppressive subtype (CK5/6+/IDO1).
 Conclusion. Expression of the IDO1 protein may serve as a molecular and biological marker allowing immunohistochemical identification of subtypes of basal-like triple-negative breast cancer.

Prognostic significance of atypical/hybrid forms of EpCAM+CD45+ cells in the blood of patients with endometrial cancer

Background. Endometrial cancer occupies a leading position in the structure of oncogynecological pathology. According to modern literature, circulating tumor cells, which represent a heterogeneous population, participate in the processes of recurrence and metastasis. Moreover, tumor cells can form hybrid forms with blood cells, increasing their malignancy.Aim. To conduct a comparative characterization of the features of the occurrence of atypical/hybrid forms of EpCAM+CD45+ cells in the blood of patients with endometrial cancer before and after surgery, and to assess their prognostic significance.Material and methods. The prospective study NCT04817501 included 55 patients with newly diagnosed T1a-2N0M0 stage endometrial cancer, average age 57.8 ± 1.7 years, who were admitted for treatment at the Research Institute of Oncology, Tomsk National Research Medical Center of the Russian Academy of Sciences and/or Tomsk Regional Oncological Dispensary. At the same time, metastases and cancer recurrences were found in 11 patients out of 55 patients after 4–5 years of follow-up after treatment. The material for the study was stabilized EDTA venous blood taken from patients before surgical treatment of the tumor and on the third day after treatment. The presence of atypical/hybrid forms of EpCAM+CD45+ cells in blood serum was determined by multicolored flow cytometry using monoclonal antibodies to CD45 and EpCAM molecules labeled with various fluorochromes.Results. When comparing the frequency of occurrence of atypical/hybrid EpCAM+CD45+ cells in patients with endometrial cancer before surgery and on the third day after surgery, no differences were found. Comparing the frequency of occurrence of atypical/hybrid forms of EpCAM+CD45+ cells in patients with endometrial cancer with hematogenous metastases and relapses and in patients with endometrial cancer without hematogenous metastases and relapses, it was found that in the blood of patients with endometrial cancer before surgery, with developed hematogenous metastases and relapses after treatment, EpCAM+CD45+ cells are more common (p = 0.03). It was found that the concentration of EpCAM+CD45+ cells in patients with established relapses and metastases of 125 (120;387) cells/ml is higher (p = 0.022) than in patients without these complications of 30 (0;220) cells/ml. During the ROC analysis, it was found that the best cut-off point for the model is the value of 80 cells/ml. The sensitivity of the model is 81.8 %, the specificity is 67.7 %. The indicator of the area under the ROC curve was 0.733.Conclusion. The number of atypical/hybrid forms of EpCAM+CD45+ cells before treatment is associated with the risk of relapses and hematogenous metastases in patients with endometrial cancer.

Antithrombotic Therapy in Patients with Paroxysmal Atrial Fibrillation after Catheter Treatment

Aim. To study the efficacy and safety of antithrombotic therapy in patients with paroxysmal atrial fibrillation (AF) after catheter treatment during 36 months of follow-up.Material and methods. The retrospective observational study included 592 patients (283 men) who underwent catheter treatment of AF, aged 26 to 86 years (median age was 61.0 [55; 67]) with paroxysmal AF, treated in cardiac arrhythmias department of the Institute of Cardiology of Tomsk National Research Medical Center from 01.01.2017 to 31.12.2019. All patients were retrospectively divided into 2 groups: the first group consisted of patients with effective AF ablation, the second - with ineffective AF ablation. During follow-up after 12, 24 and 36 months, patients' complaints, documented arrhythmia recurrences, adherence to the prescribed treatment, and adverse clinical events were taken into account.Results. In patients with paroxysmal AF, the effectiveness of catheter treatment was 73.1% after 12 months of follow-up, 69.3% – after 24 months, 71.6% – after 36 months. The analysis of our data showed that during the follow-up period of 36 months, the incidence of ischemic stroke against the background of anticoagulant therapy and effective catheter treatment of paroxysmal AF was significantly lower than in patients with unsuccessful ablation (0.3% (n=1) and 3.7% (n=4), respectively), even despite the fact that not all patients from the first group received prescribed medication.Conclusion. The use of anticoagulant therapy in patients with paroxysmal AF after interventional treatment is safe, since the invasive strategy in combination with anticoagulant therapy does not increase the risk of major and minor bleeding, and in the case of effective intervention allows statistically significantly reduce the risk of ischemic stroke and almost completely eliminate the likelihood of other thromboemolic complications.

On the 40th anniversary of the Research Institute of Medical Genetics, Tomsk National Research Medical Center

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Outcome of implementation of the project aimed to prevent cardiovascular diseases in the regional vascular center

Highlights. The article presents an analysis of the outcome of the project dedicated to cardiovascular disease prevention in the Regional Vascular Center, the analysis involved the assessment of changes in the characteristics of deceased patients. The study made it possible to identify changes in mortality rate, the impact of new diagnostic and treatment techniques and administrative decisions on the change in mortality, as well as aspects that prevent further reduction in mortality.Aim. To assess the results of the implementation of new methodological approaches to cardiovascular diseases prevention, myocardial infarction in particular, in the Regional Vascular Center.Methods. The study involved the analysis of the data (entered in real time) from the Emergency Cardiac Care Department of the Сardiology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, and data from the Department`s database containing anamnestic and clinical characteristics of patients, and recording of deaths in the period from 2014 to 2019. Statistical data processing was performed using the StatSoft Statistica software (ver. 10.0).Results. From 2014 to 2019, percutaneous coronary intervention (PCI) in myocardial infarction (MI) increased from 48 to 67.4% (p˂0.05); the primary PCI in MI with ST segment elevation (STEMI) increased from 24% to 32% (p˂0.001), the overall frequency of PCI in STEMI (primary + rescue + delayed) increased from 59.6% to 73% (p˂0.05); PCI in MI without ST segment elevation (NSTEMI) increased from 23.9% to 43.9% (p˂0.001), the frequency of intra-aortic balloon counterpulsation increased from 0.6% to 1.5% (p˂0.05), the frequency of mechanical ventilation did not change (8,3 and 8,5%), moreover the widespread use of ticagrelor and prasugrel was noted. At the same time, hospital mortality of patients with MI decreased from 9.8 to 8.0% (p>0,05): in patients with STEMI it decreased from 10.7% to 7.7% (p = 0.047), in patients with NSTEMI there was no change in mortality, it remained equal to 8–9%. Implementation of coronary reperfusion strategies that do not involve streptokinase is associated with a decrease in hospital mortality of patients with STEMI.Conclusion. The widespread introduction of modern invasive and medicinal technologies has led to a decrease in mortality of patients with STEMI. Further increasing the number of available invasive procedures – PCI, intra-aortic balloon counterpulsation and mechanical ventilation for the purposes of reducing mortality of patients with MI seems questionable.

To the 70th Anniversary of Academician of the Russian Academy of Sciences Evgeny Lhamatsyrenovich Choynzonov

On December 14, 2022, Yevgeny Lhamatsyrenovich Choinzonov, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Honored Scientist of the Russian Federation, Director of the Research Institute of Oncology of the Tomsk National Research Medical Center of the Russian Academy of Sciences, Head of the Department of Oncology of the Siberian State Medical University (Tomsk), turned 70 years old.

Structure of comorbidity in ascending aortic aneurysm

Aim. To analyze the comorbidity structure in patients with ascending thoracic aortic aneurysm (TAA) in the Siberian Federal District (SFD).Material and methods. The study included 163 patients (114 men (56,8±12,1 years) and 49 women (59,4±10,4 years)) with ascending TAA, who underwent open surgical treatment at the Cardiology Research Institute of the Tomsk National Research Medical Center. Concomitant pathologies were assessed on the basis of anamnesis and paraclinical investigations. Comparison of the prevalence of concomitant diseases in the group of patients with ascending TAA between men and women, as well as between patients ascending TAA in the SFD, other groups of patients with this pathology, population samples and patients with other cardiovascular diseases was performed using the χ2 test or Fisher’s exact test in the Statistiсa 12 program.Results. In patients with ascending TAA, hypertension (67,5%), bicuspid aortic valve (44,2%), coronary artery disease (38,6%), arrhythmia (31,3%), and heart failure (27,6%). Atherosclerosis of the aorta, coronary and carotid arteries occur with a prevalence of 12,9%, 16,6% and 5,5%, respectively. Among other forms of pathologies, the most common are connective tissue dysplasia (65,6%), obesity (12,3%), and chronic obstructive bronchitis (9,8%). In men with ascending TAA, myocardial infarction and atrial fibrillation are detected more often than women (11,4% and 20,2% vs 2% and 6,1%; p<0,05), and in women — carotid atherosclerosis and impaired cerebral circulation (12,2% and 18,4% vs 2,6% and 5,3%, p<0,05). Compared to other compared groups, aortic, coronary and carotid atherosclerosis, myocardial infarction, stroke, and type 2 diabetes were less frequently recorded in patients with ascending TAA in the SFD.Conclusion. Patients with ascending TAA in the SFD are characterized by a complex structure of comorbidity, including both cardiovascular pathologies and related risk factors, and other pathologies, including diseases of the lungs, kidneys, gastrointestinal tract, infectious and cancer diseases. To confirm the presence of inverse comorbidity between ascending TAA, atherosclerosis of other location, and type 2 diabetes, large-scale epidemiological, morphological, and molecular genetic studies are needed, which will reveal the fundamental mechanisms underlying it.

Structure of comorbidity in ascending aortic aneurysm

Aim. To analyze the comorbidity structure in patients with ascending thoracic aortic aneurysm (TAA) in the Siberian Federal District (SFD).Material and methods. The study included 163 patients (114 men (56,8±12,1 years) and 49 women (59,4±10,4 years)) with ascending TAA, who underwent open surgical treatment at the Cardiology Research Institute of the Tomsk National Research Medical Center. Concomitant pathologies were assessed on the basis of anamnesis and paraclinical investigations. Comparison of the prevalence of concomitant diseases in the group of patients with ascending TAA between men and women, as well as between patients ascending TAA in the SFD, other groups of patients with this pathology, population samples and patients with other cardiovascular diseases was performed using the χ2 test or Fisher’s exact test in the Statistiсa 12 program.Results. In patients with ascending TAA, hypertension (67,5%), bicuspid aortic valve (44,2%), coronary artery disease (38,6%), arrhythmia (31,3%), and heart failure (27,6%). Atherosclerosis of the aorta, coronary and carotid arteries occur with a prevalence of 12,9%, 16,6% and 5,5%, respectively. Among other forms of pathologies, the most common are connective tissue dysplasia (65,6%), obesity (12,3%), and chronic obstructive bronchitis (9,8%). In men with ascending TAA, myocardial infarction and atrial fibrillation are detected more often than women (11,4% and 20,2% vs 2% and 6,1%; p<0,05), and in women — carotid atherosclerosis and impaired cerebral circulation (12,2% and 18,4% vs 2,6% and 5,3%, p<0,05). Compared to other compared groups, aortic, coronary and carotid atherosclerosis, myocardial infarction, stroke, and type 2 diabetes were less frequently recorded in patients with ascending TAA in the SFD.Conclusion. Patients with ascending TAA in the SFD are characterized by a complex structure of comorbidity, including both cardiovascular pathologies and related risk factors, and other pathologies, including diseases of the lungs, kidneys, gastrointestinal tract, infectious and cancer diseases. To confirm the presence of inverse comorbidity between ascending TAA, atherosclerosis of other location, and type 2 diabetes, large-scale epidemiological, morphological, and molecular genetic studies are needed, which will reveal the fundamental mechanisms underlying it.

Evaluation of the CD40 receptor-ligand system in the patients with atrial fibrillation of non-valvular genesis

Thromboembolic syndrome is the most dangerous complication of atrial fibrillation which develops in about 8-15% of cases, thus presuming the role of persisting left-heart thrombosis in presence of anticoagulant therapy in some patients. When activated, the blood platelets express multiple copies of CD40L on their membrane. Hence, the soluble form of CD40 ligand is considered a marker of platelet activation and pathogenic processes associated with increased activity of the thrombotic system. Our aim was to study the content of CD40, soluble CD40 ligand and thrombomodulin in the patients with atrial fibrillation of non-valvular genesis receiving anticoagulant therapy, discerning those with a history of thrombotic complications, and the cases with atrial fibrillation, however, free of thrombotic complications. The study group included 22 healthy volunteers and 60 patients diagnosed with atrial fibrillation who received anticoagulant therapy, of whom 21 patients have developed thrombotic complications in the course of adequate anticoagulant therapy. Quantitative assays of CD40, soluble CD40 ligand and soluble thrombomodulin were performed by enzyme immunoassay using Core Facility “Medical Genomics”, Tomsk National Research Medical Center. Concentration of soluble CD40 ligand in both groups of the patients with atrial fibrillation significantly exceeded appropriate values in the group of healthy volunteers. CD40L content was increased in the group of patients with thrombotic complications against the group of patients without thrombotic complications. Thrombomodulin content in blood serum was decreased in the patients with thrombotic complications, as compared to both thrombosis-free patients, and to practically healthy volunteers. The study of CD40/CD40L system and thrombomodulin showed that the patients with thrombotic complications exhibited higher serum level of soluble CD40L, with a simultaneous decrease of thrombomodulin, a physiological anticoagulant. A comparative analysis of the CD40/sCD40L system showed increased concentrations of the biomarkers in females, when compared to males.

Risks and treatment for recurrent intraepithelial cervical lesions

Background. Persistently high incidence of cervical cancer in Russia and significant number of cases detected in the late stages necessitate the improvement of secondary prophylaxis of this disorder.Aim. To assess risk factors for recurrent high-grade cervical intraepithelial neoplasia (CIN2+) (high grade squamous intraepithelial lesions, HSIL) after cervical conization.Materials and methods. This study included 62 patients with recurrent HSIL treated in Novosibirsk Regional Clinical Oncology Dispensary, E. N. Meshalkin National Medical Research Center, “Zdorovye” LLC, “Avismed” LLC, Tomsk National Research Medical Center of the Russian Academy of Sciences, and Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of the Russian Federation in 2017–2021. We analyzed patients’ human papillomavirus (HPV) status, performed repeated examination of excised tissue specimens to evaluate the severity of lesions and resection margins, as well as immunohistochemical examinations. We found that mean time to cytologically confirmed recurrent HSIL was 16.0 ± 5.6 months. All patients were HPV-positive. Repeated histological examination demonstrated that 18 samples had positive resection margins or endocervical crypt involv ement. Fifty-seven samples had positive staining for p16 at immunohistochemical examination; 46 samples had Ki-67 >30 %, which indicated high risk of recurrence. Treatment of patients with recurrent HSIL included repeated excision up to healthy cervical tissues, followed by intravaginal therapy with Cervicon-DIM 100 mg twice a day (for 3 months). Follow-up examinations after 18.0 ± 6.2 months on average showed no HPV persistence and no HSIL recurrence.Conclusion. Endocervical crypt involvement along the primary resection margin, underestimated severity and depth of lesions (at the first surgery), and persistence of HPV infection are the main risk factors for recurrent cervical dysplasia or carcinoma in situ. Combination treatment that includes additional excision with a subsequent course of Cervicon-DIM is sufficient and effective.

LIMCH1 as a New Potential Metastasis Predictor in Breast Cancer.

High LIMCH1 expression in lung and renal cancer is determined as a favorable prognostic factor. However, prognostic value of LIMCH1 expression in breast cancer has not been studied yet. Therefore, this study was performed to determine the prognostic value of LIMCH1 expression in breast cancer patients. This retrospective study included 89 patients with invasive breast carcinoma of no special type. These patients referred to Cancer Research Institute of Tomsk National Research Medical Center from 2007 to 2018. LIMCH1 protein expression in tumor cells was detected by immunohistochemical analysis in this study. Statistical analysis was done to investigate the possible relationship between LIMCH1 protein expression and clinicopathological parameters, risk of metastasis, distant metastasis free survival, and overall survival. IHC analysis of breast cancer tissue samples revealed that LIMHC1 protein expression was found in 29.2% (26/89) of the cases. Lymph node and distant metastases were more frequent in patients with LIMCH1 protein expression. LIMCH1 protein expression increased the risk of distant metastasis based on our findings. LIMCH1 protein affected metastatic-free survival regardless of the T, as well as other clinical and pathological parameters (p=0.0146, HR=3.2058 (1.26; 8.17)). Moreover, LIMCH1 protein expression was associated with worse overall survival (p=0.0071, HR=2.73 (1.28; 5.85)) in our breast cancer patients. LIMCH1 protein expression was associate with metastases development, providing prognostic stratification. In breast cancer, LIMCH1 protein expression was found as an unfavorable prognostic factor of distant metastasis-free survival based on our findings.

Features of lymph node metastasis depending on intratumoral heterogeneity of non-small cell lung cancer in patients with different morphological changes in the bronchial epithelium

The aim of the study: to examine the relationship between the morphological diversity of non-small cell lung cancer and the frequency of lymph node metastasis in groups of patients with different epithelial conditions in the bronchi adjacent to the tumor. Material and methods. Surgical specimens from 90 patients with non-small cell lung cancer, who were treated in the Thoracoabdominal Department Of The Research Institute Of Oncology Of The Tomsk National Research Medical Center in the period from 2009 to 2017 were studied. The histological type of cancer was determined according to the who classification (2020). Lepidic, acinar, papillary, micropapillary, solid and solitary tumor cells were isolated in the parenchymal component of adenocarcinoma. In the parenchymal component of squamous cell carcinoma, 5 types of structures were distinguished: with keratinization, consisting of atypical cells of the prickly type without keratinization, consisting of atypical cells of the basaloid type, built of atypical cells with pronounced polymorphism, single tumor cells. Results. In patients with isolated basal cell hyperplasia, acinar (37 %), papillary (29 %) and solid (27 %) patterns were found less frequently in cases with metastatic regional lymph nodes compared to those without metastatic lymph nodes (63 %; p=0.05; 71 %; p=0.05; 73 %; p=0.01, respectively). In patients with isolated basal cell hyperplasia of the bronchial epithelium, in cases with the presence of lymph node metastasis in the parenchymal component of squamous cell carcinoma, structures 1 (with keratinization) (17 %), 2 (spiky pattern) (33 %) and 4 (polymorphic pattern) (29 %) were less frequently detected compared to those without metastases in regional lymph nodes (83 %; p=0.01; 67 %; p=0.02 and 71 %; p=0.01, respectively). In patients with a combination of basal cell hyperplasia and squamous metaplasia, a spiny pattern (65 %), a basaloid pattern (100 %), a polymorphic pattern (82 %) and single tumor cells (89 %) were more frequently detected in cases with metastatic lymph nodes than in cases without metastatic lymph nodes (35 %; р=0.04; 0 %; р=0.01; 18 %; р=0.01; 11 %; р=0.01, respectively). Conclusion. The data obtained clarify the available information on the significance of the morphological heterogeneity of the tumor for predicting the course of adenocarcinoma and squamous cell carcinoma of the lung.