Objective: to evaluate and compare the qualitative and quantitative composition of the intestinal microbiota in patients with malignant neoplasms of various localizations. Material and Methods. The study included patients who received different types of treatment in N.N. Blokhin Oncology Research Center, Moscow, Russia in 2023 for gastric cancer, including cardioesophageal adenocarcinoma (group 1), esophageal squamous cell carcinoma (group 2) and metastatic or locally advanced melanoma of the skin (group 3). All patients had to have morphologic verification of the diagnosis at the time of inclusion, be over 18 years old, have an ECOG performance status of ≤1, and have no evidence of intestinal infection, as well as not take antibiotics within 28 days prior to entry into the study. Stool samples were collected during patients’ hospitalization. The quantitative and qualitative composition of microorganisms of 17 taxonomic groups was evaluated. Microorganisms were cultured according to standard microbiological methods, taking into account the growth conditions of a particular group of microorganisms. Species identification of microbial isolates was obtained by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) and MALDI Biotyper v.3.0 software (Bruker daltonics, Germany). Descriptive statistics methods from the SPSS Statistics, v.27 software package were used. To quantitatively describe the species diversity of the gut microbiota, calculations were performed using the Margalef species richness index (d) and Shannon’s (H) diversity index. The criterion of uniformity of microbial species distribution according to their abundance in the population community was evaluated using the Pielow index (E). The Hutcheson’s T-criterion was used to test the significance of differences between sample sets of Shannon index values and to obtain statistically correct estimates of differences (p≤0.05). Results. A total of 63 samples of biological material (feces) were investigated. A change in the quantitative composition of intestinal microbiota in all study groups was found, which may have a negative impact on the general condition of the patient and the effectiveness of antitumor treatment. The increase in the proportion of Proteobacteria (Enterobacterales) can be considered as a risk factor for the development of infectious complications caused by Gram-negative microorganisms. The analysis of factors influencing the taxonomic diversity of intestinal microbiota revealed no significant differences in the composition of intestinal microbiota between the groups of patients with malignant tumors of different nosological forms (p>0.05).

Despite the use of modern treatment methods for gastric cancer (GC), survival rates in locally advanced stages remain unsatisfactory. This necessitates the search for new therapeutic options and potential predictive factors for tailoring treatment approaches. The emergence of new molecular classifications like The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG), leading to the identification of a distinct subset — gastric cancer with high microsatellite instability (MSI-H) caused by mismatch repair deficiency (dMMR), has paved the way for a novel treatment direction: immunotherapy. MSI status and PD-L1 expression are regarded as predictors of immunotherapy efficacy in GC. However, the question of which marker is more accurate or if they should be considered together remains unanswered. Furthermore, the efficacy of checkpoint inhibitor therapy is often attributed to increased PD-L1 expression in microsatellite unstable tumors compared to microsatellite stable ones. The article discusses a case demonstrating the high efficacy of immunochemotherapy, resulting in complete pathomorphological regression of the tumor in a patient with locally advanced gastric cancer and MSI-H status after neoadjuvant immunochemotherapy, despite the absence of PD-L1 expression (CPS-0). The patient has been monitored for 1.5 years post-treatment at the N. N. Blokhin National Medical Research Center of Oncology without signs of progression.

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Staging of cancer of the esophagus and esophagogastric junction (EGJ), presented in the 8th edition American Joint Committee on Cancer (AJCC). Cancer Staging was derived from the Worldwide Esophageal Cancer Collaboration (WECC). The 8th edition of the American Joint Committee on Cancer (AJCC) staging of the esophagus cancers and esophagogastric junction presents separate classifications for clinical (cTNM), pathologic (pTNM), and pathologic after neoadjuvant treatment (ypTNM). In this article changes presented between the 7th and 8th editions of this TNM classification. These changes included separate clinical, pathological and pathological prognostic staging for adenocarcinomas and squamous cell cancer.

Background. The established approach notably improving the therapeutic outcomes for locally advanced gastric cancer and gastroesophageal junction cancer, presently entails the amalgamation of perioperative chemotherapy aligned with the FLOT protocol and surgical intervention. However, this approach harbors limitations, as only half of the patient cohort successfully completes the entire prescribed course of drug therapy. The potential solution to this problem lies in the complete transfer of the chemotherapy volume to the preoperative period and the execution of total neoadjuvant chemotherapy with FLOT regimen.Aim. Aim is to conduct a comparative assessment of the efficacy and safety between total neoadjuvant and perioperative chemotherapy with FLOT regimen for patients with locally advanced gastric cancer and gastroesophageal junction cancer.Materials and methods. In a retrospective study we enrolled patients with histologically confirmed locally advanced gastric cancer and gastroesophageal junction cancer meeting clinical stage criteria T2–4 and N0–3, without of distant metastases, treated between 2014 and 2020 at Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation and Moscow City Oncologic Hospital No. 62 Department of Healthcare of Moscow. Participants in the control group underwent 8 courses of perioperative chemotherapy (4 preoperatively and 4 postoperatively), while those in the experimental group received 8 courses of total neoadjuvant chemotherapy. Both groups received drug therapy according to the FLOT protocol: 5-fluorouracil 2600 mg/m2 , intravenous drip, over 24 hours, leucovorin 200 mg/m2 , intravenous drip, oxaliplatin 85 mg/m2 , intravenous drip, docetaxel 50 mg/m2 , intravenous drip, on day 1, with a 14-day intercourse interval. The primary endpoint was one-year progression-free survival.Results. In the study included 187 patients. Participants were divided into two groups: 95 in the total neoadjuvant chemotherapy group and 92 in the perioperative chemotherapy group. The one-year progression-free survival was higher in the total neoadjuvant chemotherapy group at 79 %, compared to 68 % in the perioperative chemotherapy group (HR 0.54, 95 % confidence interval 0.32–0.9, p = 0.02). Median disease-free survival was 27.2 and 19.5 months in the neoadjuvant and perioperative chemotherapy groups, respectively. The tolerability of the entire planned drug treatment regimen was superior in the total neoadjuvant chemotherapy group, reaching 88.4 %, as opposed to 57.6 % in the perioperative chemotherapy group (p = 0.0001).Conclusion. Among patients with locally advanced gastric cancer and gastroesophageal junction cancer, the application of total neoadjuvant chemotherapy according to the FLOT protocol, administered over 8 courses, demonstrated enhanced one-year progression-free survival and improved tolerability of the entire planned treatment regimen.

Cancer is a major global health problem. The type of malignant neoplasm and the potency of the immune response against tumors are two of the key factors influencing the outcome of the disease. The degree of tumor infiltration by lymphocytes plays an important role in antitumor response development, generally correlating with a favorable prognosis of treatment for certain cancers. We analyzed the abundance of tumor-infiltrating B cells (TIBs) in solid tumors of different cancers. TIBs were shown to be more abundant in colon and sigmoid colon cancer samples compared with cecal, rectal, and kidney cancer samples. The median and interquartile range of the TIB fraction were 11.5% and 4-20% in colon cancer, 6% and 3-11% in sigmoid colon cancer, 2.7% and 0.7-3.7% in cecal cancer, 2.5% and 0.9-3.6% in rectal cancer, 1.4% and 1.0-2.3% in kidney cancer, and 3.0% and 1.8-12% in lung cancer, respectively. However, there were no significant differences in the abundance of TIBs among samples at different stages of the cancer. Hence, investigation of the B cell response in colon cancer is of particular interest, since increased quantities of TIBs may indicate the existence of immunogenic tumor markers or the cell-cell interactions involved in disease progression. We believe that studying the diversity of TIBs in colon cancer will increaseour understanding of the mechanisms of the disease, contributing to the identification of new molecular targets for targeted oncotherapy.

Introduction. There is a lack of evidence of BAP1 expression on patient prognosis, that indicates the need for further study of this topic.Aim. To evaluate BAP1 expression level in clear cell kidney cancer patients.Materials and methods. We included in a retrospective study based on N.N. Blokhin National Medical Research Center of Oncology database from 2009 to 2013 patients with clear cell kidney cancer, who were divided into 2 groups depending on BAP1 status. Primary endpoints were BAP1 expression level, 5-year overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS).Results. 40 patients were included in the BAP1+ group, 53 patients – in the BAP1– group. There were no statistically significant differences in parameters that could affect the prognosis between our groups. 5-year OS was higher in the BAP1+ group (76.0 %) compared to BAP1– (58.0 %) (p = 0.040). There were no statistically significant differences between 5-year DFS and CSS.Conclusions. BAP1+ patients had significantly higher OS, but BAP1 mutation didn’t affect DFS and CSS.

Staging of cancer of the esophagus and esophagogastric junction (EGJ), presented in the 8th edition American Joint Committee on Cancer (AJCC). Cancer Staging was derived from the Worldwide Esophageal Cancer Collaboration (WECC). The 8th edition of the American Joint Committee on Cancer (AJCC) staging of the esophagus cancers and esophagogastric junction presents separate classifications for clinical (cTNM), pathologic (pTNM), and pathologic after neoadjuvant treatment (ypTNM). In this article changes presented between the 7th and 8th editions of this TNM classification. These changes included separate clinical, pathological and pathological prognostic staging for adenocarcinomas and squamous cell cancer.

Background. Signet ring cell gastric carcinoma of the stomach traditionally characterized by its poor prognosis. Survival of patients with signet ring cell gastric carcinoma regardless of the stage of the disease has not been well studied.Aim. To compare clinicopathological characteristics and survival of the patients with signet ring cell gastric carcinoma of the stomach and non-signet ring cell carcinoma depending on the stage of the disease.Materials and methods. We performed retrospective review was undertaken of patients with gastric cancer who received surgical treatment in period from 2013–2018.Results. At early signet ring cell cancer, the 3and 5-year survival rates was 100,0 and 89.0 %; for non-signet ring cell carcinoma 91.4 and 85.3 % (р = 0.6; Hazard Ratio (HR) 0.73; 95 % Confidence Interval (CI) 0.22–2.42) respectively. For advanced signet ring cell carcinoma, the median survival rates, 3and 5-year survival rates was 38 months, 53.0 and 38.4 %; for non-signet ring cell carcinoma 51.1 months, 59.2 and 48.0 % (р = 0.2; HR 1.2; 95 % CI 0.91–1.54).Conclusion. Long-term results in patients with early (T1) signet ring cell cancer of the stomach did not significantly differ in comparison with other histological types of gastric cancer. Long-term results of advanced signet ring cell cancer are worse than non-signet ring cell cancer, but the differences are not statistically significant.

Purpose of the study. To determine the influence of prognostic factors on survival rates in patients with metastatic renal cell carcinoma (mRCC) aged ≥ 75 years.Materials and methods. A retrospective study included 77 mRCC patients aged ≥ 75 years who received systemic therapy at the Municipal Oncologic Hospital No. 62 in Moscow and the Municipal Oncologic Dispensary in St. Petersburg from 2006 to 2019. Clinical data from medical records were obtained and analyzed retrospectively, all patients underwent clinical, laboratory, and pathomorphological examination. Patients' survival rates were evaluated using the statistical method of survival time analysis (Survival Analysis). Descriptive characteristics of survival time were calculated in the form of life tables, and Kaplan-Meier curves were constructed.Results. In the present study, a favorable prognosis according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)was noted in 20.8 % of patients with mRCC aged ≥ 75 years; 6.5 % had solitary metastases. The 3- and 5-year survival rates were 35.8 % and 21.2 %.In single-factor analysis in mRCC patients ≥ 75 years of age, it was found that ECOG status (p < 0.001), histological subtype (p = 0,01), Fuhrman grade of tumour differentiation (p = 0.003), type of metastases (p = 0.045), liver metastases (p < 0.001), IMDC prognosis (p = 0.042) and nephrectomy (p = 0.014).Conclusion. In a multivariate analysis, factors affecting survival in patients with mRCC aged ≥ 75 years included sex, histologic subtype, number of metastases, bone and lymph node metastases, IMDC prognosis, and radiation therapy and nephrectomy. Further studies are needed to identify additional personalized prognostic factors in elderly patients with mRCC.

The Russian consensus on prevention, diagnostic and treatment of gastric cancer was prepared on the initiative of the Moscow clinical scientific center named after A. S. Loginov according to the Delphi method. Its aim was to clarify and consolidate the opinions of specialists on the most relevant issues of prevention, diagnosis and treatment of gastric cancer. An interdisciplinary approach was provided by the participation of leading gastroenterologists, oncologists and surgeons.

The objective was to demonstrate a clinical case of iatrogenic injury of the trachea, which, despite its large size (length 65, width up to 25 mm), wastreated conservatively and, thus, avoided risks for the patient associated with the need for technically complex surgical intervention.Materials and methods. A 65-year-old patient diagnosed with peripheral cancer of the lower lobe of the left lung pT2aN0M0 stage IB, who routinely underwent thoracoscopic left lower lobectomy with mediastinal lymph node dissection. During anesthesia, tracheal intubation with a double-lumen tube of the R. Shaw type was carried out with technical difficulties; during intubation, a defect in the posterior wall of the trachea in its membranous part was formed. The defect was diagnosed on the first postoperative day.Results. Despite the large size of the tracheal defect, the patient had no symptoms of respiratory failure, and there were also no signs of mediastinitis or damage to the esophagus, which almost completely covered the resulting hole in the posterior wall of the trachea. Such circumstances made it possible to avoid a potentially dangerous and complex surgical intervention, carry out conservative therapy and wait for the resulting defect to heal through granulation tissue. Enhanced antimicrobial therapy was carried out; in order to sanitize the tracheobronchial tree and monitor healing, fiber-optic bronchoscopy was performed, which made it possible to clearly demonstrate both the damage itself and the stages of its healing.Conclusions. The described case clearly demonstrates the potential for healing of even very extensive tracheal wall defects with conservative therapy. However, it is important to note that success in this clinical case was the result of a combination of circumstances – only the membranous part of the trachea was damaged; the defect was almost completely covered by the intact esophagus, which reduced the risk of developing mediastinitis and prevented the development of severe pneumomediastinum and subcutaneous emphysema. There were no signs of respiratory failure. The patient was transferred from the intensive care unit on the 13th day of the postoperative period, discharged from the hospital on the 22nd day.

Results: the incidence of postoperative complications was 33,8% (22/65), mortality – 3,1% (2/65); with phased tactics, these figures were 31,7% (19/60) and 3,3% (2/60); after simultaneous operations – 60% (3/5) and 0%, respectively. When performing operations for lung cancer after preliminary myocardial revascularization, the incidence of postoperative myocardial infarction was 3,3% (2/63), with a fatal outcome of 1,6% (1/63). In the long term, the total 1-, 3- and 5-year survival rate of radically operated patients was: at stage I – 95,7%, 86,3%, 64,7%, with II – 82,6%, 62,4%, 49,9% and at III – 66,0%, 55,8% and 34,3%, respectively (p = 0,042). Conclusions: the implementation of prophylactic myocardial revascularization in patients with lung cancer with severe forms of concomitant coronary artery disease allows to expand the group of radically operated patients, to achieve satisfactory immediate and long-term treatment results. Key words: lung cancer, coronary artery disease, lobectomy, bilobectomy, pneumonectomy, coronary artery bypass surgery, coronary angioplasty

3D printing has opened new opportunities for the development of personalized systems for prosthetics of extensive chest wall defects after radical surgical interventions for malignant tumors. However, risk factors for an adverse outcome of such operations have not yet been identified. Clinical cases . A 65-year-old man with primary chondrosarcoma of the V rib, underwent surgical resection of three ribs, plasty with local tissues, and an individual 3D printed titanium implant was installed on the sternum and IV-VI ribs. Follow up for 26 months showed no complaints or signs of recurrence. A 52-year-old woman with radiation-induced soft tissue sarcoma of the chest wall, that developed 9 years after radiation for breast cancer, underwent resection of four ribs and pectoral muscles and a 3D printed titanium implant was installed on the sternum and II-V ribs. The operation was complicated by the marginal necrosis of the soft tissue flap and infection of the endoprosthesis, which required removal of the metal structure and reconstruction using TRAM flap. After 9 months, a local recurrence of the tumor was diagnosed. Discussion. As a factor of a positive outcome in a man should be noted a thick layer of subcutaneous fat with muscle tissue, due to which plastic surgery was performed, covering the defect without tension. An extensive resection of the pectoral muscles in a woman created a tissue deficit. Another factor of an unfavorable outcome can be considered the radio-induced nature of the sarcoma. Further research is needed to improve the strategy for selecting patients with malignant tumors of the chest wall for prosthetics.

Introduction. Primary spinal osteosarcoma and rare metastatic heart lesion are considered significant factors for poor prognosis. The available work indicates that combined treatment, including the radical surgery of heart solitary metastatic lesion, probably provides the best outcome.Case report. Man, 27-year-old, with Th8 spinal osteosarcoma and solitary left atrial metastasis. From October 2019 to February 2020 5 cycles of chemotherapy (high doses of platinum and doxorubicin) were carried out with positive effect. Next steps were surgery: March 2020 – spondylectomy of the Th8 vertebra with combined stabilization; September 2020 – subtotal resection with plasty of the right atrium, tricuspid valve and prosthesis of the right coronary artery. Between the first and second surgery, 4 more same chemotherapy cycles were carried out. Currently, 24 months after completion of treatment, there are no signs of the disease.Conclusion. The article presents a unique case of treatment of primary osteosarcoma and metastatic lesion of rare location. Multidisciplinary approach and combination treatment in specialized centers increase the probability of favorable outcome in such cases.

Особенности клеточного иммунитета медицинских работников в первую волну пандемии SARS

Objective . To conduct a systematic analysis of data on the results of studies published in scientific journals on the pro-carcinogenic and anticarcinogenic role of microbiota, as well as on the therapeutic potential of microorganisms in oncogenesis. Material and Methods . The articles were searched using the Web of Science, Scopus, PubMed, Medline, and eLIBRARY databases. More than 150 sources dedicated to the study of the carcinogenic function of the microbiota and the possible influence of its species and quantitative composition on the efficacy and toxicity of antitumor therapy were found. Data from 71 articles were included in the review. Results . The relationship between the gut microbiota and cancer is multifactorial and bilateral: pro-carcinogenic on the one hand and anti-carcinogenic on the other hand. Microorganisms can induce tumor growth and cancer development through DNA damage and induction of mutagenesis, trigger oncogenic signals, disruption of barrier function, as well as immune response system disruption. Depletion of microbiota, the development of dysbiosis and induction of chronic inflammatory state are negative factors in the development of cancer. The anticancer effect of microorganisms is presumably based on the production of tumor-suppressive metabolites that function through multiple immune reactions. Maintenance of barrier function, competitive exclusion of pathogenic bacteria, and direct action on immune cells to prevent inflammation are also important protective factors. The presence of intratumor microorganisms in various tumors has been noted. Changes in species and quantitative composition of cancer patients’ microbiota are influenced by diet, taking antibacterial drugs, chemo-, immuno- and radiation therapy. In turn, the microbiota can affect the ongoing treatment. Numerous studies on the influence of the gut microbiota on the efficacy of immunotherapy, particularly in disseminated melanoma, have been conducted. It has been suggested that primary resistance to immunotherapy may be related to the abnormal composition of the gut microbiota. The level of gut microfora composition diversity and the number of Faecalibacterium or Bacteroidales in the fecal microbiota have been suggested to be the predictor of response to anti-PD-1 therapy. To change the composition and activity of the gut microbiota, several therapeutic methods, such as the administration of prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, as well as the change in the microbiota composition through a specific diet, are available.

Introduction : The results of six randomized control trials have been published by 2022, which evaluated the efficacy of adding PD-1 inhibitors to the first-line chemotherapy in patients with metastatic esophageal cancer. However, it still remains unclear which patients derive the most clinical benefit from combined therapy. Therefore, it is necessary to evaluate the efficacy of the combination of anti-PD1 treatment with chemotherapy in different patient subgroups. Materials and methods : We conducted a meta-analysis of randomized controlled trials in patients with stage IV esophageal cancer who received anti-PD1 drugs with different chemotherapeutic regimens in the first-line setting to select patients who benefit the most from the combined therapy. Results : Six randomized trials were included in the analysis for a total of 3,813 patients. Patients who received combination therapy had significantly longer OS (HR = 0.69, 95% CI: 0.63-0.75; p < 0.001), PFS (HR = 0.62, 95% CI: 0.56-0.69; p < 0.001), and better ORR (OR = 2.12, 95% CI: 1.85-2.42; p < 0.001) than those who received chemotherapy alone. Subgroup analyses showed no benefit of adding PD1-inhibitors to chemotherapy in patients with PD-L1 CPS <1 in terms of OS (HR = 0.58, 95 % CI: 0.31-1.1; p = 0.1) as well as in never-smokers (HR = 0.9, 95% CI: 0.67-1.23; p = 0.52). Conclusions : The addition of PD-1 inhibitors to the first-line chemotherapy in patients with metastatic esophageal cancer significantly improves treatment outcomes. Our results could not strongly suggest the selected patients' cohort which would benefit the most from the combination of PD-1 inhibitors and chemotherapy use.