OBJECTIVE:To study the features of gastric neuroendocrine tumors (NETs) and the diagnostic and prognostic significance of PDX-1 expression in them.MATERIAL AND METHODS:207 NETs identified in 56 men and 115 women (59 had multiple NETs), and 94 cases of gastric cancer (comparison group) were studied morphologically and immunohistochemically.RESULTS:In more than half of the cases (54.93%), NETs were localized in the body of the stomach; the cardiac and antral parts of the stomach accounted for 8.64% and 11.73%, respectively. NETs of the cardiac region predominated in men, and of the body and antrum - in women. NETs of the cardiac region predominated in men, and of the body and antrum - in women. The vast majority of NETs were highly differentiated (89.20%), of which Grade 1, 2 and 3 were 55.41%, 40.76% and 3.82%, respectively. Neuroendocrine carcinomas (NEC) accounted for 10.80% of all NET cases. NECs were more often localized in the cardiac part of the stomach and accounted for 35.71% of all NETs in the cardiac part. The share of NEC among all NETs of the antrum was 15.79%, of the body of the stomach - only 3.37%. Metastases were found in 17.90% of NETs. Expression of PDX-1 was detected in 44.73% of NETs, 70% of NECs and 74.50% of gastric cancers.CONCLUSION:PDX-1 is involved in the mechanisms of precancerous and cancerous lesions of the stomach and its overexpression is detected in the majority of the most malignant NETs and gastric cancers.

This publication examines the endoscopic semiotics of non-small cell lung cancer. It presents many years of experience in bronchoscopic studies of various forms of central lung cancer growth, the nuances of endoscopic diagnostics, interpretation of the detected changes, and discusses options for performing a biopsy.

Neuroendocrine tumors are a large and heterogeneous group of tumors that develop from neuroendocrine cells. To define this type of tumor, the well-established term “carcinoid” continues to be used in clinical practice for years. In accordance with the characteristics of embryogenesis, three groups of neuroendocrine tumors are distinguished. The source of these tumors are neuroendocrine cells, which are located in almost all organs. The term itself and the concept of “neuroendocrine cell” have historically been repeatedly reassessed. In 1969 A. Pearse, based on the ability of these cells to utilize and decarboxylate amine precursors, introduced the term “APUD system” (aminoprecursor uptake and decarboxylation). Neuroendocrine cells, although they can secrete the same substances as neurons, but, unlike the latter, they participate not in topical, but in paracrine regulation of organs and tissues. They are located in all human organs and are the most important tool for maintaining homeostasis. In recent years, more and more publications have appeared about the frequent localization of neuroendocrine tumors in the lungs, and new approaches to the diagnosis of this pathology. This review presents the diagnostic features and clinical course of pulmonary neuroendocrine tumors.

This publication examines the possibilities of bronchoscopy in the diagnosis of primary small cell lung cancer and the assessment of the effectiveness of treatment. Endoscopic semiotics of small cell lung cancer is considered. A clinical observation of a patient with widespread small cell lung cancer is presented: primary diagnosis and assessment of the effectiveness of the course of chemotherapy.

Adverse events affecting the cardiovascular system are one of the most serious problems in the general management of patients with oncological diseases, since they can jeopardize the success in the treatment of malignant neoplasms. Despite modern methods of treatment, some chemotherapeutic drugs, such as anthracyclines, HER2 /ErbB2 inhibitors can have a pronounced effect on the cardiovascular system. These toxic effects lead to cardiac arrhythmia, heart failure, vascular toxicity and even death. It is important for oncologists and cardiologists to understand the basic diagnostic and treatment strategies that should be used in the event of toxicity of this kind.

КЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ ХИРУРГИЯ■ ФУНДАМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ И МЕЖДИСЦИПЛИНАРНЫЕ ТЕХНОЛОГИИ Актуальность.Феномен опухолевого почкования (tumor budding -Bd), определяемый как появление единичных или изолированных (до 4) кластеров опухолевых клеток в инвазивном компоненте карциномы, впервые был описан в 1954 г.Однако лишь в 2016 г., согласно ITBCC (International Tumor Budding Consensus Conference), были выпущены рекомендации по системе оценки Bd для колоректальной аденокарциномы.Согласно многочисленным исследованиям, на сегодняшний день определение опухолевого почкования при колоректальном раке является независимым прогностическим фактором как общей, так и безрецидивной выживаемости.Несмотря на схожую гистологическую картину с опухолями с кишечным иммунофенотипом, на сегодняшний день имеются лишь единичные работы о значимости опухолевого почкования при ампулярной карциноме (АК).Цель -изучение феномена опухолевого почкования при кишечном типе АК.Материал и методы.Избирательно исследован операционный материала 36 пациентов от 51 года до 83 лет (средний возраст -65 лет), перенесших панкреатодуоденальную или гастропанкреатодуоденальную резекцию по поводу АК с января 2017 по декабрь 2021 г.Количественно оценивали феномен опухолевого почкования, согласно рекомендациям ITBCC (International Tumor Budding Consensus Conference).С помощью корреляционно-регрессионного анализа оценивали силу и значимость связи между опухолевым почкованием и характеристиками первичной опухоли, степенью ее дифференцировки, показателями периневральной и периваскулярной инвазии, показателями регионарного метастазирования.Результаты.В 91,7% случаев (33/36) ампулярная карцинома представлена опухолью низкой степени злокачественности (low-grade).В 53,8% (19/36) случаев выявлена инвазия в мышечную оболочку стенки двенадцатиперстной кишки (рТ2); в 44,3% случаев (16/36) стадия определена как рТ3, т.е.имелась инвазия в головку поджелудочной железы.И лишь в 1% случае опухоль ограничена ампулой большого дуоденального соска (рТ1).Поражение регионарных лимфатических узлов отмечено в 50,0% (18/36) случаев и выявлено как при прямом, так и при метастатическом распространении карциномы.При высокодифференцированных формах и микропапиллярном гистологическом типе АК ни в одном случае не выявлено феномена опухолевого почкования.Оно выявлено в 27,7% случаев (10/36) и обнаружено во всех случаях низкодифференцированных форм.При этом для опухолей G2 степень Bd не превышала 5-7 на 0,785 мм 2 .Высокий процент опухолевого почкования связан с плохо дифференцированными формами (р=0,0067, R=0,43).Чем выше Bd-значение, тем чаще обнаруживали метастазы в регионарных лимфатических узлах (p=0,0054, R=0,67, R=5,75, 95% доверительный интервал 3,20-10,32).Во всех случаях с наличием периневральной инвазии выявлен высокий процент опухолевого почкования -Bd 2-3 (p=0,008, R=0,69).Заключение.Учитывая наличие корреляционной зависимости количества опухолевых кластеров при почковании и инвазивного потенциала опухоли со степенью дифференцировки первичной опухоли, частотой регионарного метастазирования и наличием периневральной Опухолевое почкование (tumor budding) во взаимосвязи с инфильтративным потенциалом ампулярной карциномыЕремеева Е.Р. 1 , Сетдикова Г.Р. 1, 2 , Вербовский А.Н. 1 , Семенков А.В. 1, 3 , Шикина В.Е. 1 1 Государственное бюджетное учреждение здравоохранения Московской области «Московский областной научно-исследовательский клинический институт имени М.Ф.Владимирского», 129110, г.Москва, Российская Федерация 2 Государственное бюджетное учреждение здравоохранения города Москвы «Московский клинический научно-практический центр имени А.С.Логинова Департамента здравоохранения города Москвы», 111123, г.Москва, Российская Федерация 3 Федеральное автономное образовательное учреждение высшего образования Первый Московский государ-

Cardioncology has emerged as a new field at the intersection of cardiology and oncology. Despite the fact that improving efficiency of antitumor treatment increased the survival of oncological hematological patients, the long-term cardiovascular consequences of this treatment have become more clinically significant.Despite the effectiveness of modern methods of treatment, some drugs, such as Bcr-Abl kinase inhibitors, anthracyclines, HER2/Erbb2 inhibitors, vascular endothelial growth factor inhibitors, fluoropyrimidines, as well as radiation therapy can have a pronounced effect on the cardiovascular system. These toxic effects lead to cardiac arrhythmia, heart failure, vascular toxicity and even death. It is important for hematologists, oncologists and cardiologists to understand the basic diagnostic and treatment strategies that should be used in the event of toxicity of this kind. At a time when, due to the developed cardiotoxicity, antitumor therapy should be discontinued, in some cases, it is possible to consider continuing treatment with caution and careful monitoring.

Introduction. The standard of 1st line treatment of HER2+ metastatic breast cancer (mBC) is double blockade with trastuzumab and pertuzumab + taxane, 2nd line – Trastuzumab-emtazine. There are no standards for further treatment, as well as the optimal drug sequence. Expansion of the arsenal of therapeutic possibilities and the use of new combinations will certainly improve the results of treatment of this category of patients and increase their life expectancy.Aim. We sought to describe treatment patterns of eribulin and clinical outcomes of metastatic HER2-positive breast cancer treated with eribulin plus trastuzumab combination in academic institutions and community oncology practices across the Russian Federation.Materials and methods. Patients treated with eribulin anytime between Jan, 2014 and Sep, 2019 with a diagnosis of MBC were identified by 23 providers from Russia. Providers retrospectively reviewed the health records and abstracted selected data points into an electronic case report form for each eligible patient.Results. 100 HER2-positive pts received eribulin in combination with trastuzumab. Median age was 55 (31–80) yrs and ECOG status 0–3. 67% pts had visceral metastases. Eribulin was administered as 1st and 2nd line to 23 (23%) pts, 3rd line to 31 (31%) pts, 4th line and later to 46 (46%). Median number of cycles was 5 (2–27). ORR was 12%, SD – 72%, SD > 6 months – 23%, PD – 16%. Clinical efficacy rate achieved in 35%. Median PFS was 5.07 months (95% CI 4.021–6.119). According to the ER-status the response to eribulin and trastuzumab was different. ORR was 18.8%, SD 72.9% in pts with ER-positive MBC (n = 48) and 5.8% and 71.2% respectively in ER-negative MBC (n = 52). Median PFS was 6.97 months (95% CI 3.924–10.016) in pts with ER-positive MBC and 4.67 months (95% CI 3.841–5.499) in ER-negative MBC (р = 0.3). The combination was well tolerated: dose reductions were required in 12% pts, withdrawal due to toxicity in 4% pts. The most common type of toxicity was hematological with neutropenia Gr III-IV in 14 (14%) pts. Peripheral neuropathy Gr III was observed in 5 (5%) pts. No cardiotoxicity was detected.Conclusions. This is the real-life data of clinical outcomes for patients receiving eribulin plus trastuzumab for HER2-positive MBC throughout the Russian Federation. Our experience with eribulin plus trastuzumab demonstrates that this combination may be a potential effective treatment option for HER-2 positive MBC patients.

Целью настоящего сообщения является анализ собственных клинических данных о целесообразности применения афатиниба во II линии терапии при аденокарциноме легкого.На базе МОНИКИ накоплен материал по 12 пациентам с аденокарциномой легкого, получавших II линию терапии

Introduction. The randomized MPACT study showed that nab-paclitaxel plus gemcitabine results in statistically significantly longer life expectancy. The objective of this retrospective study is to obtain relevant data on the efficacy of this combination in real clinical practice in Russia. Materials and methods. The study included patients with morphologically proven locally advanced or metastatic pancreatic cancer, with a general condition assessed on the ECOG scale between 0-2, which received gemcitabine and nab-paclitaxel. Immediate and long-term treatment outcomes were evaluated. Results. 142 patients, who received treatment from 2009 to 2019 in 17 centers from 11 regions of Russia, were included in the study. Assessment of the objective effect was made in 134 patients. Objective effects were detected in 34 (25.4%) cases. The median time-to-progression was 6.1 months (95% confidence interval (CI) 4.8-7.4), the median length of life was 14.2 months (95% CI 10.6-17.9). An elevated CA19-9 level is the only independent adverse prognostic factor for progression-free survival (RR = 8.0, 95% CI 1.4 -43.8, p = 0.02) according to Cox multivariate regression analysis. The number of previously conducted chemotherapy lines (p = 0.34), ECOG status (p = 0.70), age over 70 years (p = 0.45), serious comorbidity (p = 0.97) did not have a statistically significant effect on progression-free survival. Findings. The gemcitabine and nab-paclitaxel combination has a relatively higher efficacy in advanced pancreatic cancer. The immediate and long-term results of its use in real clinical practice in Russia are consistent with data obtained in the Western countries.

Introduction.Eribulin, an non-taxane microtubule inhibitor, has been registered in Russia for patients with locally advanced or metastatic breast cancer (mBC) who received at least one chemotherapy regimen for a advanced disease, previous therapy should include anthracyclines and taxanes in adjuvant or metastatic setting, except the patients who could not be prescribed these drugs. We present our experience with eribulin in real clinical practice in Moscow and the Moscow Region.Patients and methods. We conducted a retrospective analysis of the experience with the use of eribulin in Moscow and the Moscow Region in 202 patients with mBC from January 2016 to February 2017 to assess the effectiveness and safety of the drug. All patients received previous therapy with anthracyclines and taxanes for locally advanced and / or metastatic cancer. The average age of patients at the time of inclusion in the analysis was 5 years (28–81). The status of the general condition on the ECOG 0-1 scale was registered in 81.3 % (100 / 123) of patients, the status of ECOG 2-3 in 18.7 % (23 / 123) of patients. The median of the number of courses of chemotherapy with eribulin is 4 (2–17). Patients received eribulin in 1-7 chemotherapy lines for metastatic disease. The average number of affected organs is 2 (1–5).Results.Complete response (CR) was in 3 (2 %) patients. Partial response (PR) was in 24 (15.7 %) patients, stabilization of the disease – in 89 (58. 2 %). Progression of the disease was recorded in 37 (24.1 %) patients. The median of progression-free survival (PFS) on the therapy was 4.64 (95 % CI 2.97-6.87) months. Stabilization of the disease for more than 6 months was registered in 28 (18.3 %) patients. The most significant toxicity was neutropenia and polyneuropathy (21 patients (10.4 %) and 7 patients (3.5 %), respectively).Dose reduction due to neutropenia was required by 26 patients (12.9 %). The objective response rate (ORR) depended on the chemotherapy line: in 1-3 lines the efficacy of the treatment was higher: the ORR was 21.6 %, compared to the 4th and subsequent lines – 12.3 %, respectively. With HER2-positive mBC, eribulin showed clinically significant results in combination with trastuzumab.Conclusions.Our analysis confirms that eribulin has a predictable and manageable safety profile, is an effective drug for the treatment of patients with different subtypes of mBC in a real clinical setting.

Introduction. Eribulin, an non-taxane microtubule inhibitor, has been registered in Russia for patients with locally advanced or metastatic breast cancer (mBC) who received at least one chemotherapy regimen for a advanced disease, previous therapy should include anthracyclines and taxanes in adjuvant or metastatic setting, except the patients who could not be prescribed these drugs. We present our experience with eribulin in real clinical practice in Moscow and the Moscow Region. Patients and methods . We conducted a retrospective analysis of the experience with the use of eribulin in Moscow and the Moscow Region in 202 patients with mBC from January 2016 to February 2017 to assess the effectiveness and safety of the drug. All patients received previous therapy with anthracyclines and taxanes for locally advanced and / or metastatic cancer. The average age of patients at the time of inclusion in the analysis was 5 years (28–81). The status of the general condition on the ECOG 0-1 scale was registered in 81.3 % (100 / 123) of patients, the status of ECOG 2-3 in 18.7 % (23 / 123) of patients. The median of the number of courses of chemotherapy with eribulin is 4 (2–17). Patients received eribulin in 1-7 chemotherapy lines for metastatic disease. The average number of affected organs is 2 (1–5). Results. Complete response (CR) was in 3 (2 %) patients. Partial response (PR) was in 24 (15.7 %) patients, stabilization of the disease – in 89 (58. 2 %). Progression of the disease was recorded in 37 (24.1 %) patients. The median of progression-free survival (PFS) on the therapy was 4.64 (95 % CI 2.97-6.87) months. Stabilization of the disease for more than 6 months was registered in 28 (18.3 %) patients. The most significant toxicity was neutropenia and polyneuropathy (21 patients (10.4 %) and 7 patients (3.5 %), respectively). Dose reduction due to neutropenia was required by 26 patients (12.9 %). The objective response rate (ORR) depended on the chemotherapy line: in 1-3 lines the efficacy of the treatment was higher: the ORR was 21.6 %, compared to the 4th and subsequent lines – 12.3 %, respectively. With HER2-positive mBC, eribulin showed clinically significant results in combination with trastuzumab. Conclusions. Our analysis confirms that eribulin has a predictable and manageable safety profile, is an effective drug for the treatment of patients with different subtypes of mBC in a real clinical setting.