Background. Currently, low-dose computed tomography (LDCT) is the only screening test that reduces the risk of death from lung cancer. However, there are a number of disadvantages, such as lack of widespread use, high cost, high false-positive rate and the need to conduct studies only in high-risk groups, which significantly limit mass screening. exhaled breath analysis, which uses sensitive breath sensors, is a promising method to improve early diagnosis of lung cancer. Cancer Research Institute of Tomsk National Research Medical Center together with Tomsk State University and Tomsk Polytechnic Research Institute has developed a gas analysis complex capable of analyzing the gas composition of exhaled air with remote sampling from bags. during the study, data obtained by digitizing signals from gas analysis system sensors and patient metadata are recorded in a database for subsequent automated processing and analysis using a neural network. Case description. A 48-year-old female patient with a long history of smoking came to the clinic of the Cancer Research Institute for consultation with suspected pathological infiltration around the celiac trunk detected by abdominal CT. As a clinical trial of the developed gas analytical complex for cancer detection, a sample of exhaled air was taken, and the comparison of the composition of volatile organic compounds (VOCs) with that in the control group (healthy individuals) revealed abnormalities characteristic of lung cancer. the patient underwent a chest CT scan, which revealed stage IIB peripheral cancer of the lower lobe of the left lung. the original sensor gas analysis complex, which has no analogues in Russia, was used for the first time in the detection of lung cancer. the data obtained allowed us to suspect the presence of lung tumor in the patient and perform radical surgical treatment. the composition of VOCs in exhaled air was assessed on day 10 after surgery, and no significant changes in the composition of exhaled air were observed. Conclusion. Machine learning algorithms are actively used to diagnose socially significant diseases. the platforms being developed based on arrays of chemical sensors with data analysis using a neural network are promising candidates for implementation in screening activities.
Relevance. Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide due to the high recurrence and metastasis rates. It is generally accepted that metastases and recurrences are formed by tumor cells with a highly invasive, stem and chemoresistant phenotype. Tumor hybrid cells (THCs) formed by the fusion of tumor cells with a wide range of normal cells: macrophages, fibroblasts, mesenchymal stem cells, etc. are considered to be potential metastasis and recurrence-initiating cells. However, the phenotypic diversity of THCs, and their association with disease progression remain poorly understood. The aim of the study was to characterize the population composition of THCs in NSCLC and its association with clinicopathological characteristics, metastasis and recurrence. Materials and Methods. A total of 50 patients with NSCLC were included. Fresh frozen samples of tumor tissue obtained during resection and morphologically verified were used to analyze types and number of THCs. THCs were analyzed by flow cytometry in primary tumors using markers for tumor cells, cancer stem cells, leukocytes, macrophages and fibroblasts. Results and Discussion. THCs were detected in all NSCLC patients. Most THCs demonstrated leukocyte, macrophage and stem characteristics. The number and frequency of THCs depended on neoadjuvant chemotherapy. THCs with leukocyte and stem cell markers (pan-CK+CD45+CD44+CD73+) were associated with locoregional recurrence, whereas THCs with macrophage and stem cell markers (EpCAM+CD45+CD44+CD73+CD163+) — with distant metastases. Conclusion. This study is the first to comprehensively describe the population composition of THCs in NSCLC, their association with clinicopathological characteristics, neoadjuvant chemotherapy and disease prognosis. Detection of prognostically relevant THCs could be an effective approach for predicting the risk of metastasis and recurrence of NSCLC and the basis for the development of therapy focused on the prevention of cancer progression.
Surgery is the standard of care for non-small cell lung cancer (NSCLC). The overall survival rates especially in patients with locally advanced lung cancer are low. The resistance of cancer cells to chemotherapeutic drugs reduces the efficacy of treatment. Special attention is paid to the feasibility of assessing the tumor sensitivity to certain chemotherapy drugs. Currently, the most studied predictors are monoresistance and multidrug resistance genes, such as ABCC5, RRM1, ERCC1, BRCA1, TOP1, TOP2a, TUBB3 and TYMS.The aim of the study was to analyze the outcomes of combined modality treatment using radical surgery and personalized adjuvant chemotherapy for stage II–III NSCLC.Material and Methods. The study included 120 patients with stage II–III NSCLC, who underwent radical lung resection with mediastinal ipsilateral lymph node dissection. The patients were then divided into two groups. The main group consisted of 60 patients who received personalized platinum-based adjuvant chemotherapy based on the expression levels of the genes, such as ABCC5, RRM1, ERCC1, BRCA1, TOP1, TOP2a, TUBB3 and TYMS. The control group consisted of 60 patients who received postoperative chemotherapy empirically.Results. In the main group, disease progression occurred in 14 out of 60 patients, three-year disease-free survival (DFS) was 76.7 % (the median was not reached). In the control group, DFS was 53.3 % (28 out of 60 patients), the median was 31.0 (4–36 months); the differences were statistically significant: Logrank test χ2 =4.382 p=0.036. The overall three–year survival rate was 90.0 % in the main group (6/60 patients died) and 61.7 % in the control group (23/60 patients died), the differences were statistically signifcant: Logrank test χ2 =6.915, p=0.009.Conclusion. The personalized adjuvant chemotherapy resulted in the improved three-year relapse-free and overall survival rates in NSCLC patients.
The treatment of non-small-cell lung cancer (NSCLC) continues to be a pressing issue. It is therefore necessary to advance and to put into practice the methods that will improve patients survival. The aim of the study was to estimate available information on application of intraoperative radiation therapy (IORT) in combined treatment of patients with NSCLC. The treatment plans, safety and tolerability of the treatment method were evaluated. From data analysis it became clear that IORT is a topical treatment for operable non-small cell lung cancer (NSCLC). The new technology has proved its effectiveness due to the reliable local control and significant improve the late survival of patients. During the IORT high one-off dose is selectively delivered to the tumor or tumor bed with maximum preservation of the adjacent normal tissues. The key point in planning radiation exposure during the IORT is to calculate accurately the single radiation dose. The reduction of local relapses and the improvement in overall survival are most likely due to the IORT damaging effect on possible tumor microfoci located in the bronchus cult, its surrounding tissues and lymphatic outflow pathways. To date, further study of the IORT effectiveness and feasibility will remain relevant. However, intraoperative irradiation has already proved to be an effective component of a multimodal approach to cancer treatment.
Early prediction and prevention of recurring illness is critical for improving the survival rates of patients with non-small cell lung cancer (NSCLC). Previously, we demonstrated that the presence of premalignant epithelial changes in the small bronchi distant to the primary tumor is associated with NSCLC progression: isolated basal cell hyperplasia (iBCH) indicates a high risk of distant metastasis, BCH combined with squamous metaplasia (BCH SM ) - a high risk of locoregional recurrence. Here, we aimed to identify germline single nucleotide variants (SNVs) and insertions and deletions (InDels) associated with distant metastasis and locoregional recurrence in cases with iBCH and BCH (SM )using whole-exome sequencing of 172 NSCLC patients. The rs112065068 of the TGOLN2 gene was identified only in iBCH patients and was associated with a high risk of distant metastasis ( P < .001) and worse metastasis-free survival (HR = 4.19 (95 %CI 1.97 -8.93); P < .001). This variant was validated in a group of 109 NSCLC patients using real-time PCR and Sanger sequencing analyses. To our knowledge, this study is the first to identify a germline variant associated with NSCLC distant metastasis.
Background. Lung cancer has long been the most common type of cancer in the male population (16.4%). The incidence of lung cancer among women is increasing worldwide. In Russia, as of 2022 (compared to 2013), lung cancer shifted to the second place in the structure of cancer incidence among males, following prostate cancer. However, the anticipated rise in new cases of this pathology requires an analysis for evaluating and adjusting the current anti-cancer programs. Objective. To analyze the incidence rates and quality of oncological care provided for malignant neoplasms of the lung in the Siberian Federal District within 2013–2022. Methods. A retrospective observational study was conducted utilizing depersonalized data on the prevalence and structure of malignant neoplasms derived from the reports of the Siberian Federal District subjects, the Russian Federation (form No. 7 “Information on Malignant Neoplasms” and form No. 35 “Information on Patients with Malignant Neoplasms”), as well as from the Russian Federal State Statistics Service. The primary indicators of the study included the proportion of lung cancer within the structure of cancer incidence in men and women (C33.0, 34.0–C34.9 according to the ICD-10 classification), standardized incidence rates of lung cancer in men and women, age-specific incidence rates of lung cancer in men and women, by-stage distribution of the lung cancer tumor process, morphological verification, active case finding, one-year mortality, and the proportion of patients with malignant lung neoplasms who were registered for five years or more, uptake ratio of lung cancer population, ratio of one-year mortality to stage IV cases of the previous year. The calculations of standardized and age-specific incidence rates were performed using ONCOSTAT, while the quality indicators of oncological care were assessed using the Cancer Care Indicators software. Standardized incidence rates were calculated according to SEGI age standardization. Statistical analysis of qualitative indicators of medical care provided to patients with malignant neoplasms of the lung over time was conducted using linear regression analysis methods; statistical significance was evaluated at p ≤ 0.05. Results. A decrease in lung cancer incidence among men was observed in the Siberian Federal District, whereas the level of this indicator among women remained unchanged. The comparison of oncological care indicators for lung cancer patients in 2013 and in 2022 revealed several notable changes. The proportion of morphologically verified malignant neoplasms increased from 72.9% to 87.9%. The percentage of cases diagnosed at stages I-II grew from 24.2% to 29.1%, while the proportion of patients registered for five years or more increased from 37.3% to 43.4%. The uptake ratio of lung cancer population extended from 2.2 to 2.7. Conversely, the one-year mortality rate decreased from 55.2% to 47.8%, and ratio of one-year mortality to stage IV cases of the previous year diminished from 1.3 to 1.0. However, a number of advanced cases grew from 39.4% to 40.6%. Conclusion. The conducted epidemiological analysis revealed a decrease in the incidence of lung malignancies among men (from 63.9 to 57.5 cases per 100,000 population) and stagnation of the incidence rate among women (approximately 10.1 cases per 100,000 population) in the Siberian Federal District during the study period. The proportion of lung cancer within the structure of cancer incidence in men reduced from 21.5% to 17.6%. Key indicators of the quality of medical care provided to patients with lung malignancies demonstrate a positive trend; however, the proportion of cases diagnosed at stage IV appears pessimistic (40.6%). The obtained data necessitates the development and implementation of preventive measures for early diagnosis, including screening programs, as well as educational activities aimed at healthcare professionals and the general population, to promote healthy lifestyles and enhance oncological awareness.
Background. Despite advances in surgical and therapy techniques, non-small cell lung cancer (NSCLC) is one of the most common cancers and the leading cause of cancer-related death. Therefore, it is increasingly important to search for markers that predict the risk of tumor progression. The study of the morphology of the epithelium of the bronchi of different calibers has great potential for solving this problem. The aim of the study was to comparatively evaluate the characteristics and frequency of occurrence of various combinations of morphological changes in the epithelium of the bronchi of large and small calibers in patients with lung squamous cell carcinoma and lung adenocarcinoma. Material and methods. lung samples were collected from 151 NSCLC patients (stage T1–4N0–3M0), who underwent surgery at the cancer Research institute, TNRMC. Various morphological changes in the bronchial epithelium were analyzed. Results. The study of the frequency of occurrence of various morphological changes in small-caliber bronchi showed that basal cell hyperplasia occurred in 90.8 % of cases. Diffuse isolated basal cell hyperplasia was observed in 33.8 % of cases. Focal basal cell hyperplasia was diagnosed in 38.4 % of cases. A combination of basal cell hyperplasia with squamous metaplasia was observed in 18.5 % of cases. The study of the frequency of occurrence in large-caliber bronchi demonstrated that basal cell hyperplasia was the most common morphological variant (93.4 %, including diffuse isolated basal cell hyperplasia in 33.8 % and focal basal cell hyperplasia in 38.4 %). The combination of basal cell hyperplasia and squamous metaplasia was found in 19.8 %. The combination of basal cell hyperplasia with squamous metaplasia and dysplasia was found in 1.3 % compared to the epithelium of small-caliber bronchi. Conclusion. The obtained results on the frequency of occurrence of morphological changes in large-caliber bronchi are of theoretical interest for further research to identify groups at high risk of progression of non-small cell lung cancer.
Background:Peritoneal carcinomatosis (PC) is one of the most unfavorable sites of metastasis for malignant tumors of various localizations, especially gastric cancer (GC). According to the literature, synchronous PC in GC is common in 15-52% of patients. The purpose of this study was to examine the long-term results using personalized systemic and intraperitoneal chemotherapy as part of the combined treatment of stomach cancer presenting with synchronous PC.Methods:Cytoreductive surgical treatment was performed for 70 patients at the first stage. The control group (n = 35) received standard postoperative chemotherapy according to the FOLFOX scheme. Personalized postoperative systemic and intraperitoneal chemotherapy was administered in the basic group (n = 35), based on the expression levels of the eight genes in the primary tumor, lymph node, and peritoneal metastases.Results:The median progression-free survival was 14.9 months in the basic group, and in the control group it was 11.2 months (P < 0.001). The median life expectancy in the basic group was 16.8 (13.7 - 18.8) months, in the control group it was 12.5 (11.3 - 13.1) months (P < 0.001).Conclusions:Developing algorithms of personalized systemic and intraperitoneal chemotherapy in patients with GC with synchronous carcinomatosis, based on the analysis of molecular genetic characteristics of the tumor and metastases, allows to improve the long-term results of combined treatment.
Peritoneal carcinomatosis is associated with poor prognosis in gastric cancer patients. Stage IV gastric cancer (GC) is diagnosed in 39.8 % of patients; local metastases without evidence of distant metastases occur only in 18–20 % of stage IV gastric cancer patients. The purpose of the study was to estimate the efficacy of personalized chemotherapy in the combined modality treatment of patients with stage IV GC with peritoneal carcinomatosis. Material and Methods. Cytoreductive surgery was performed in 70 patients with GC with peritoneal dissemination. The control group patients (n=35) received postoperative chemotherapy with the FOLFOX regimen. The study group patients (n=35) received personalized systemic and intraperitoneal chemotherapy based on the expression of chemosensitivity and resistance genes. Results. The median survival time (18.7 months) in the study group patients was higher than that in the control group and in studies described in the world literature (CRS + HIPEC). Personalized chemotherapy improved median progressionfree survival (PFS) by 4.6 months (29.1 %) and median overall survival (OS) by 6 months (32 %) compared to FOLFOX regimen chemotherapy. In the study group, the 1-, 2and 3-year survival rates were observed in 35 (100 %), 9 (27 %) and 1 (3 %) patients, respectively. Conclusion. Personalized chemotherapy in the combined modality treatment can improve long-term treatment outcomes (longer median PFS and OS) in GC patients with peritoneal dissemination.
Цель исследования. Изучить образцы выдыхаемого воздуха, полученных от больных раком легкого, а также найти общие сигнальные маркеры, которые можно выявить с помощью искусственной нейронной сети, обеспечивающей единообразие процедуры отбора проб на основе стандартизированной сенсорной системы газоанализа. Материалы и методы. В ходе исследования образцы выдыхаемого воздуха были взяты у 90 человек в возрасте от 22 до 95 лет за период 2020-2021 гг. Все испытуемые, участвовавшие в исследовании, были разделены на две группы: первую — тестовую и вторую — контрольную. В основную группу вошли пациенты с морфологически верифицированным злокачественным новообразованием легких стадии Т1-4N0-3M0-1 (21 человек). В контрольную группу вошли лица, у которых на момент исследования не было клинических данных о наличии злокачественной патологии (из анамнеза или по данным ранее проведенного обследования, если таковые имеются). Разработан газоаналитический комплекс, способный анализировать газовые пробы в двух режимах — прямое вдыхание в камеру или использование мешков для газовых проб. В данной работе мы использовали дистанционный отбор проб из мешков в связи с пандемией COVID-19. Результаты. Точность диагностики рака легкого составила 85,71 %, чувствительность — 95,24 % и специфичность — 76,19 %. К отличительным особенностям изученного нами метода можно отнести мобильность используемого оборудования и возможность размещения в медицинских учреждениях разного уровня, простота и относительная дешевизна диагностики, возможность беспрепятственного использования с целью скрининга опухолевых процессов в широкой популяции.
Introduction. To date, one of the reasons for the ineffectiveness of chemotherapy in various malignant neoplasms, including lung cancer, is the formation of the multidrug resistance (MDR) phenotype in tumor cells, which is caused by the expression of ABC transporter genes.Aim. The aim of this work was to assess the expression of ABC-transporter genes during chemotherapy and to analyze the relationship with the effectiveness of chemotherapy and prognosis of the disease.Materials and methods. We used biopsy and surgical material from 91 patients with stage IIB–IIIA non-small cell lung cancer (NSCLC). The treatment regimen included: 2 courses of neoadjuvant chemotherapy (NAC), surgery and 3 courses of adjuvant chemotherapy (ACT) with platinum doublets. RNA was isolated from the samples, followed by quantitative PCR to assess the expression of genes ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2.Results and discussion. It was shown that the level of expression of the studied genes was not associated with the effect of NAC in patients with lung cancer, except for the ABCC5 gene, which showed a relationship at the level of a pronounced trend (p = 0.07). It was also shown that in the group of patients with an objective response to chemotherapy, the frequency of decreased expression of the ABCC1 (p = 0.01) and ABCC5 (p = 0.004) genes was statistically significantly higher than in the group of patients with stabilization. Further, using the Kaplan – Meier method, it was found that a decrease in expression is associated with high rates of metastatic-free survival (MFS). The highest rates of 5-year MFS (more than 85 %) are observed in patients with a decrease in the expression of the ABCB1 and ABCG2 genes, log-rank test p = 0.0007 and p = 0.002, respectively.Conclusion. Thus, it has been shown that changes in the expression of ABC transporter genes are associated with the effectiveness of chemotherapy and the prognosis of the disease. The data obtained can be used as a basis for the detection of potential drug targets.
Background. Neuroendocrine tumors (NETs) of the small bowel are rare and slow-growing tumors arising from intraepithelial endocrine cells that synthesize serotonin. Diagnosis of these tumors poses a signifcant challenge because they are often not diagnosed until an advanced stage, since the tumor may be asymptomatic or accompanied by non-specifc gastrointestinal complaints. Approximately 40 % of patients develop carcinoid syndrome due to hormonal activity of NETs. Surgery is the mainstay treatment of locoregional small bowel NETs. The fve-year survival rate of patients is about 85 %, with a median rate of 9.3 years. Case description. The female patient complained of facial redness and, to a lesser extent, redness of the skin of the trunk, accompanied by a feeling of heat, severe headache, lacrimation, and general feeling of weakness. The patient unsuccessfully received symptomatic treatment prescribed by various specialists (gynecologist, therapist, psychiatrist, endocrinologist, etc.) for 14 years. Based on the comprehensive examination, NET of the small bowel was diagnosed. The patient underwent radical surgery (pT2N1M0, stage IIIB, G2), but taking into account the unfavorable prognostic factors (metastases in the mesenteric lymph node, presence of carcinoid syndrome, elevated biochemical markers, Ki67 level = 6 %, presence of somatostatin receptors of 2 and 5 types in 60 % of tumor cells), the patient was further treated with somatostatin analogues. Conclusion. When small bowel NETs are suspected, especially with the evidence of carcinoid syndrome, every effort should be made to confrm the diagnosis using a combination of anatomical and functional tumor imaging with biochemical markers.
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.
Objectives: A growing body of evidence suggests the important role of chemosensitive gene expression in the prognosis of patients with lung cancer. However, studies on combined gene expression assessments for personalized prescriptions of chemotherapy regimens in patients have not yet been conducted. The aim of this work was to conduct a prospective study on the appointment of personalized chemotherapy in patients with non-small-cell lung cancer. Materials and methods: The present study analyzed 85 patients with lung cancer (stage IIB-IIIB). Within this group, 48 patients received individualized chemotherapy, and 37 patients received classical chemotherapy. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 in lung tissues were measured by quantitative real-time PCR (qPCR), and an individual chemotherapy regimen was developed for each patient according to the results. Patients in the classical chemotherapy group received the vinorelbine/carboplatin regimen. Survival analyses were performed using the Kaplan–Meier method. Prognostic factors of metastasis-free survival (MFS) and overall survival (OS) of patients were identified via Cox’s proportional hazards regression model. Results: MFS and OS were significantly better in the personalized chemotherapy group compared to the classic chemotherapy group (MFS, 46.22 vs. 22.9 months, p = 0.05; OS, 58.6 vs. 26.9 months, p < 0.0001). Importantly, the best metastasis-free survival rates in the group with personalized ACT were achieved in patients treated with the paclitaxel/carboplatin regimen. Based on an assessment of chemosensitivity gene expression in the tumors, the classical chemotherapy strategy also increased the risk of death (HR = 14.82; 95% CI: 3.33–65.86; p < 0.000) but not metastasis (HR = 1.95; 95% CI: 0.96–3.98; p = 0.06) compared to the group of patients with chemotherapy. Conclusions: The use of combined ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 gene expression results for personalized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity.
Till now the facilities of MRI with paramagnetic contrast enhancement (CE-MRI) in detection of lung tumors remain underused and almost ignored. A clinical case of primary detection and prospective follow-up of lung cancer in a patient whose MRI of the chest revealed a tumor lesion — a central cancer of the left lung, in particular a lesion of the bronchus of the lower lobe of the left lung. MRI of the chest with paramagnetic contrast enhancement was carried out as part of the whole body CE-MRI study after the complex therapy of breast cancer, and both the primary lung tumor and metastatic lesion of mediastinal — subbifurcation lymph nodes were revealed. With a transbronchial biopsy, the diagnosis of lung cancer was verified. Chemotherapy (ChT) was started using the vinorelbin/ carboplatin regimen. After this, the CE-MRI has been carried out during the whole period of followup of anti-cancer chemotherapy. At the CE-MRI during the first course of ChT visually the complete regression of the disease, also with clinical remission was achieved. However, the ChT scheme was not fully completed due to the patient’s departure for urgent private reasons. Two months later, the patient was examined again according to the same CE-MRI protocol, while a relapse of the disease was detected with a more pronounced lesion of the mediastinal lymph nodes than during the initial treatment. ChT with vinorelbine/carboplatin was again carried out under the control CE-MRI, this time completely. According to the chest CE-MRI, visual remission was achieved, with the disappearance of nodular tumor at the site of the previously identified primary tumor of lung cancer and metastatic lesions of lymph nodes. Thus, it was the CE-MRI which provided the early diagnosis and adequate control of treatment of the lung cancer with extensive local lymph nodes spread. After this CE-MRI, the whole body PET with 18F-fluorodeoxyglucose (FDG) was also performed and no signs of relapse or continued tumor growth were revealed. Five months after this stage, the patient did persist to stay completely preserved clinically, at work and socially active. Thus, the chest CE-MRI can be employed for the follow-up of the tumor process in lung cancer, as necessary, without radiation exposure, without limiting the number and frequency of studies.
INTRODUCTION: Clinical observations ascertain a comorbid development of chronic obstructive pulmonary disease (COPD) and lung cancer (LC). Here, a more favorable prognosis for patients with LC depends on detection of the disease in early stages, when radical treatment is possible. This determines the importance of a detailed examination of the function of the external respiration using modern methods to identify predictors of lung cancer. AIM: To study the peculiarities of disorders in the apparatus of external respiration (AER) in patients with LC developed with the underlying COPD (LC + COPD). MATERIALS AND METHODS: A clinical and functional examination of 33 individuals was conducted — 10 healthy (control group), 12 patients with COPD and 11 patients with LC + COPD, using methods of spirography, pneumotachography and body plethysmography. RESULTS: In patients with COPD, as well as in those with LC + COPD, a statistically significant decrease in the median values of vital capacity of lungs (VCL), forced expiratory volume in 1 second (FEV1), flow-volume curve (PFER, MEF50, MEF75) and an increase in respiratory minute volume (RMV), residual lung volume (RLV), the ratio of residual lung volume to total lung capacity (RLV/TLC) and bronchial resistance (Raw) were revealed. It was found that in patients with LC + COPD, the median values of VСL, RLV/TLC, Raw did not differ, while the values of flow-volume curve were reduced as compared to patients with COPD. The observed decrease in the air flow rate parameters in the absence of differences in Raw indicates the extrapulmonary causes of these changes. CONCLUSION: In the course of the study, high reserve capacities of the apparatus of external respiration were found. The obtained parameters turned out to be of low informative value for diagnosis of development of LC with the underlying COPD. In patients with LC + COPD, the study of AER function, in addition to spirography and pneumotachography, should include body plethysmography, to avoid overdiagnosis of broncho-obstructive syndrome.
Background . To select the optimal treatment for non-small cell lung cancer (NSCLC), it is important to predict the risk of distant metastasis and the effectiveness of therapy. The effect of neoadjuvant chemotherapy (NAC) on distant metastasis remains poorly understood. In this study we evaluated the feasibility of predicting the risk of distant metastasis and effectiveness of various treatment options for pre- and intraoperative therapy in NSCLC patients with high and low risk of distant metastasis, divided based on the assessment of morphological changes in the epithelium of small bronchi located near the primary tumor. Material and Methods . The study included 171 patients with NSCLC (T1-4N0-3M0). Various premalignant lesions: isolated basal cell hyperplasia (BCH+SM-D-), basal cell hyperplasia with squamous cell metaplasia (BCH+SM+D-) and squamous cell metaplasia with dysplasia (BCH-SM+D+) were identified in the bronchial epithelium of small bronchi taken at a distance of 3–5 cm from the tumor. Preliminary studies have shown that the detection of BCH+SM-D- or BCH-SM+D-in small bronchi are the markers of high risk of NSCLC distant metastasis, and the detection of BCH+SM+D- and BCH-SM-D- are the markers of low risk of NSCLC distant metastasis. 52.6 % of patients (90/171) received 2–3 courses of neoadjuvant chemotherapy (NAC), 41.1 % (37/90) of patients underwent intraoperative radiation therapy (IORT) at a single dose of 10–15 Gy and 47.4 % (81/171) of patients received platinum-based adjuvant chemotherapy (AC). Results . Both treatment options (NAC+IORT+ and NAC+IORT–) effectively reduced the incidence of distant metastases in the high-risk group patients during the first 2 years of follow-up compared with the high-risk group patients who did not received therapy. In the low-risk group patients, distant metastases rarely occurred, regardless of the treatment option. Adjuvant chemotherapy was found to have no influence on the frequency of distant metastases. Metastasis-free and overall survival rates were better in the low-risk group patients or in patients who received the NAC+IORT+ regimen. Conclusion . Combination of NAC and IORT resulted in the increase in metastasis-free and overall survival rates.
Introduction. To date, the molecular mechanisms underlying the development of STAS remain poorly understood. The development of STAS – a marker of an unfavorable outcome of lung cancer – is likely to be associated with markers of a high risk of hematogenous metastasis and recurrence, i.e., changes in the bronchial epithelium.The paper aimed to study the features of STAS in patients with different morphological changes in the bronchial epithelium. Materials and methods. We studied surgical material from 90 patients with non-small cell lung cancer who received combined treatment in the thoracoabdominal department of the Research Institute of Oncology of the Tomsk National Research Medical Center between 2009 and 2017. Case histories and outpatient cards of patients were analyzed. We determined the prevalence of the disease according to the international classification using the TNM staging system (2017). We used the standard method to post the material and manufacture histological preparations. The 2015 WHO classification was used to determine the histological type of cancer. The study included only cases with non-small cell lung carcinoma, namely squamous cell carcinoma (n=50) or adenocarcinoma (n=40). In the lymph nodes, we assessed the presence of metastatic lesions and counted the number of lymph nodes with metastases. In the bronchial mucosa located 3–4 cm from the border of the tumor, we assessed the presence of changes in the bronchial epithelium. The information about the presence, timing, and location of hematogenous metastases and relapses was taken into account. We used descriptive statistics; the results were discussed with the statistically significant difference at p<0.05. Results. We identified a number of patterns that could complement the understanding of SPAS pathogenesis, a form of tumor progression relevant for lung cancer. Conclusion. We propose to consider the detection of STAS as an unfavorable prognostic sign associated with the risk of locoregional metastasis. Keywords: STAS, non-small cell lung cancer, regenerative hyperplasia of the bronchial epithelium, metaplasia of the bronchial epithelium, metastasis
Gastric cancer (gc) is one of the most common cancers worldwide. The majority of newly diagnosed gastric cancer cases present with distant metastases. Peritoneal carcinomatosis (pc) is the most unfavorable type of progression of primary gc, which occurs in 14–43 % of patients. The purpose of the study was to highlight modern approaches to the treatment of gc with pc. Material and methods. We analyzed 136 publications available from pubmed, medline, cochrane library, and elibrary databases. The final analysis included 46 studies that met the specified parameters. Results. The modern approaches to the treatment of gc with peritoneal carcinomatosis were reviewed, namely: cytoreductive surgery (crs), combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (crs/hipec); neoadjuvant intraperitoneal/systemic chemotherapy (nips) and pressurized intraperitoneal aerosol chemotherapy (pipac). The results of large randomized trials and meta-analyses were analyzed. Benefits and limitations of these trials were assessed. Conclusion. The peritoneal cancer index (pci) and the level of cytoreduction are two key prognostic factors for increasing the median overall survival. By reducing tumor volume through cytoreductive surgery, it is possible to allow tumor cells to re-enter the proliferative phase of the cell cycle and make them more sensitive to antitumor agents. The hematoperitoneal barrier is the main reason that prevents the effective delivery of drugs from the systemic bloodstream to the abdominal cavity, which is why the effect of systemic chemotherapy on peritoneal metastases is extremely limited. Intraperitoneal chemotherapy offers a more effective and intensive regional therapy, creating a so-called «depot» of a chemotherapy drug, thereby prolonging the effect of the administered drugs. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (crs + hipec) using the combination of surgical resection, cytotoxic chemotherapy, hyperthermic ablation of the tumor and hydrodynamic flushing, is a promising approach in the treatment of gc with peritoneal carcinomatosis.
To date, the role of human papillomavirus (HpV) in the development of lung cancer is still under investigation. The available published data do not provide evidence of the involvement of HpV in lung cancer pathogenesis. In Russia, there are no reports regarding the studies of viral contribution to lung carcinogenesis. The aim of the present study was to examine the presence of high-risk HpV infection in patients with non-small cell lung cancer (NSCLC). Material and Methods . The study included 30 patients with histologically verified stage IIBIIIA NSCLC. Normal and tumor lung tissue samples as well as whole blood samples from each patient were used. dNA was isolated from tissue samples using the QIAamp dNA mini Kit (Qiagen, Germany). Amplisens® reagent kits (Moscow, Russia) were used for dNA isolation and genotyping. Results . The presence of HpV dNA was detected in 3 (10.0 %) patients. HpV dNA was not detected in 27 (90.0 %) patients. HpV-16 genotype was observed in 2 HpV-positive patients, and HpV-33 was observed in 1 patient. A clinically insignificant viral load was found in almost all HpV-positive samples. The assessment of the virus integration in HpV16-positive lung cancer patients revealed mixed and integrated forms of the virus in the tumor tissue of these patients. The 5-year metastasis-free survival rate in all HpV-positive patients was 100 %. Conclusion . Our data showed HpV dNA prevalence rate of 10 % among NSCLC patients in the Russian population. The presence/absence of a viral component for lung cancer patients is a clinically significant parameter.