EPIDEMIOGICAL STUDIES
The aim of the study was to estimate the incidence and mortality rates in patients with colorectal cancer in the Russian Far east in the time period from 2008 to 2020. Material and methods. Cancer incidence and mortality data collected from population-based cancer registries were used. Results. In 2020, the average rate of colorectal cancer incidence in the Russian Far east was 15.29 ± 0.33 per 100,000 men (2019: 15.35 ± 0.36) with an annual percent decrease of 5.40% since 2008. The corresponding rate increased to 12.92 ± 0.23 (2019: 12.98 ± 0.25) per 100,000 women with an annual percent increase of 5.95 %. By the end of the study period the number of new cancer cases increased to 13.2 % (2008: 1.3 %). The percent of morphological confirmation of the diagnosis was lower than in the Russian Federation as a whole (93.4 % versus 96.0; 2008: 84.3 %). The number of patients followed-up for 5 and more years was lower than in the Russian Federation as a whole (52.7 % versus 55.0 %; 2008: 41.9 %). The quality of the cancer service activity was marked by the index of reliability of registration, which was not lower than 0.40 in any of the territories of the district. The average colorectal cancer mortality rate in men was 8.73 ± 0.12 per 100,000 population (2019: 8.72 ± 0.13), which exceeded that in women (6.83 ± 0.10; 2019: 7.37 ± 0.53). The death rate within the first year after diagnosis decreased to 25.0 % (2008: 34.3 %). Conclusion. Unfortunately, the work of primary healthcare organizations responsible for early detection of cancer has not led to significant changes in the incidence rates. (2020: 13.02 0/0000; 2008: 12.9858 0/0000) and mortality rates (2020: 7.4558 0/0000; 2008: 7.6158 0/0000). Cancer screening programs aimed not only at the early cancer detection, but also at the formation of groups being at high risk of cancer are necessary for improving cancer care in the Russian Far east region. These programs should be accompanied by the training of professional staff and the development of modern diagnostic and treatment regimens.
Background. Small intestine cancer is extremely rare cancer worldwide with an incidence of less than 1.0 per 100,000 population. In 2020, 1,711 cases of small intestine cancer were recorded in Russia, including 781 cases among the male population, and 930 among the female population. It should be noted that in Russia, despite the decrease in the total number of new cancer cases associated with the coronavirus epidemic, the number of patients with small intestine cancer increased by 4.14 % from 2019 to 2020. In the Northwestern Federal district of the Russian Federation, 216 patients with newly diagnosed small intestine cancer were registered in 2020, (29 more patients than in the previous year). The purpose of the study was to analyze the efficiency of small intestine cancer care provision based on of the database of the population cancer Registry (db pcr) of the Northwestern Federal district of the Russian Federation, with an assessment of one- and five-year survival rates. Material and methods. To calculate the survival rates for patients with small intestine cancer, we selected 1922 patients from the database of the pcr of the Northwestern Federal district of the Russian Federation, for the period from 2000 to 2018. Standard methods for calculating survival rates according to the eurocare program were used. Results. The one-year survival rate of small intestine cancer patients increased from 50.0 % to 61.1 % from 2000 to 2018, and the five-year survival rate remained almost unchanged. The relative one-year survival rate of patients was 2.0 % higher. The five-year survival rate for five-year cohorts indicates defects in staging of small intestine cancer rather than an improvement in patient care; although this rate increased from 31.5 to 32.9 %. The histological detail of small intestine cancer according to the icd-10 was investigated. Conclusion. The study confirmed the high mortality rates and modest survival benefits in survival rates in patients with small intestine cancer. Defects in the distribution of patients by disease stages were revealed. The most common histological types of small intestine cancer with calculations of patient survival were identified.
CLINICAL STUDIES
The aim of the study was to evaluate the feasibility of using single-photon emission computed tomography (SPECT) with [99mTc]Tc-1-THIO-D-glucose in the detection of brain tumor malignancy. Material and methods. The study included 70 patients diagnosed with grade II–Iv malignant brain tumors and 10 patients with benign brain tumors. The control group consisted of 20 patients who had no pathological changes in the brain at the time of diagnosis. All patients underwent single-photon emission computed tomography of the brain 40 minutes after intravenous injection of [99mTc]Tc-1-THIO-D-glucose at a dose of 500 MBq. The [[99mTc]Tc-1-THIO-D-glucose radiopharmaceutical was prepared directly in the nuclear medicine department in strict accordance with the instructions. The head and neck of the patient fell into the field of view of the detectors of the gamma camera, 32 projections were recorded in a matrix of 256×256 pixels without hardware magnification. High-resolution low-energy collimators were used. Results. In patients with verified diagnosis of malignant brain tumors, SPECT with [99mTc]Tc-1-THIO-D-glucose correctly visualized tumors in all cases. The tumor was visualized as a zone of increased accumulation of [99mTc]Tc-1-THIO-D-glucose of varying intensity and size. However, benign brain lesions did not show [99mTc]Tc-1-THIO-D-glucose uptake. Physiological accumulation of [99mTc]Tc-1-THIO-D-glucose was observed in soft tissues of the aponeurotic helmet, the choroid of the brain, the mucous membranes of the nasal cavity, and the sinuses of the skull bones. Pathological changes in the brain revealed by SPECT were confirmed by MRI with contrast enhancement. Conclusion. The study demonstrated a high efficiency of SPECT with [99mTc]Tc-1-THIO-D-glucose in visualization of malignant brain tumors. The sensitivity, specificity and accuracy of SPECT with [99mTc]Tc-1-THIO-D-glucose in the imaging of malignant brain tumors were 93–100 %, 65–100 %, 95–100 %, respectively. The data obtained suggest that [99mTc]Tc-1-THIO-D-glucose SPECT as an additional method for the detection of malignant brain tumors can increase access to radionuclides for this group of patients and improve the quality of cancer care.
ABC-transporter family genes have been well studied and their involvement in the development of drug resistance has been assessed. The presence of aberrant conditions in these genes can affect the treatment and prognosis of the disease. Loss of heterozygosity (LOH) is one of these conditions; it is a common event in cancer development. therefore, The aim of this study was to investigate the relationship between LOH in ABC transporter genes in breast cancer and response to chemotherapy and disease prognosis. Material and methods. a total of 130 breast cancer patients were included in the study. microarray analysis was performed on Affymetrix Cytoscantm HD Array high-density DNA chips to assess LOH status. Chromosome Analysis Suite 4.1 software (Affymetrix, USA) was used to process microarray results. Results. Forty-nine ABC transporter genes were evaluated for LOH. the frequency of LOH ranged from 6.9 % to 90 %. an association analysis identified two genes: ABCG5 and ABCG8, in which the presence of LOH was associated with a lack of objective response to neoadjuvant chemotherapy. the presence of LOH in the ABCA5, ABCA6, ABCA8, ABCA9, ABCA10 and ABCC3 genes was associated with high rates of metastasis-free survival (log-rank test, p<0.04). Conclusion. The presence of loss of heterozygosity in the ABC transporter genes was found to have no significant effect on the response to chemotherapy. However, a high prognostic potential of ABCA family genes was found.
LABORATORY AND EXPERIMENTAL STUDIES
Purpose of the study: to assess the relationship between atypical/hybrid forms of EpCAM+CD45+ cells in ascitic fluid of ovarian cancer patients and the levels of cancer markers, such as CA125 and HE4, and the tumor grade. Material and methods. The study included 48 patients with newly diagnosed ovarian cancer (42 patients with stage Ic–IV ovarian cancer and 6 patients with borderline ovarian tumors (Bots). The age of the patients ranged from 36 to 76 years. the study material included ascitic fluid and blood samples. the presence of atypical/hybrid forms of EpCAM+CD45+ cells in ascitic fluid was identified by laser multicolor flow cytometry. The levels of CA125 and HE4 markers were measured by ELISA. Results. The number of EpCAM+CD45+ cells in ascitic fluid of patients with serous ovarian carcinoma was 1.02 (0.30; 2.68) cells/µl (0.55 (0.03; 4.51) cells/µl in patients with low-grade serous carcinoma (LGSC) and 1.36 (0.41; 2.68) cells/µl in patients with high-grade serous carcinoma (HGSC). The number of EpCAM+CD45+ cells in ascitic fluid of serous ovarian carcinoma was shown to have a strong correlation with СА125 and HE4 levels in blood serum (R=0.60; р<0.01 and R=0.34; р=0.05, respectively). In the LGSC group, there was a strong direct correlation between the number of EpCAM+CD45+ cells in ascitic fluid and the levels of CA125 and HE4 markers in blood serum (R=0.93; p<0.01 and R=0.68; p=0.03, respectively). No differences in the levels of EpCAM+CD45+ cells in ascitic fluid and CA125/ HE4 markers in blood serum between patients with HGSC and LGSC were found. the levels of atypical/hybrid forms of cells in ascitic fluid and CA125/ HE4 markers in blood serum were significantly lower in patients with Bots than in patients with serous ovarian carcinoma (p=0.02 for EpCAM+CD45+ cells and p<0.01 for СА125/ HE4 levels). Conclusion. The relationship between the number of EpCAM+CD45+ cells in ascitic fluid and the levels of CA125 and HE4 markers in blood serum of patients with serous ovarian carcinoma was found. However, no differences in the levels of EpCAM+CD45+ cells in ascitic fluid and CA125/ HE4 markers
in blood serum between patients with HGSC and LGSC were observed.
The study was aimed to determine the level of class G antibodies specific to Bp, Es, Pg (IgG-Bp, IgG-Es, IgG-Pg) in patients with colorectal and breast cancers. Material and methods. The content of these antibodies in the blood serum of healthy women (n=401), patients with colorectal cancer (n=219) and patients with breast cancer (n=1469) was studied using a non-competitive enzyme immunoassay. Statistical analysis of the results was performed using the Statistica 8.0 software. Results. The levels of IgG-Bp >7 and IgG-Es>6 were higher in patients with colorectal cancer than in healthy controls (66 % vs 25 %, p<0.0001, OR=5.9 and 58 % vs s 45 %, p=0.002, OR=1.7, respectively). The individual antibody ratios of IgG-Bp/IgG-Es >1, IgG-Bp/IgG-Pg>1.5, and IgG-Es/IgG-Pg>1.5 were also higher in patients with colorectal cancer than in healthy controls (74 % vs 34 %, p<0.0001, OR=5.6; 75 % vs 28 %, p<0.0001, and 58 % vs 38 %, p<0.0001, OR=2.3, respectively). Compared to healthy controls, breast cancer patients had higher values of IgG-Bp >6 (57 % vs 33 %, p<0.0001, OR=2.7) and IgG-Es>5 (62 % vs 53 %, p=0.003, or=1.4) and ratios of IgG-Bp/IgG-Es>1 (55 % vs 34 %, p<0.0001, or=2.4), IgG-Bp/IgG-Pg>1.3 (71 % vs 36 %, p<0.0001, or=4.5) and IgG-Es/IgG-Pg>1.4 (62 % vs 44 %, p<0.0001, or=2.1). Compared to breast cancer patients, colorectal cancer patients had higher values of IgG-Bp>7 (66 % vs 50 %, p<0.0001) and the ratios of igg-Bp/IgG-Es >1 (74 % vs 55 %, p<0.0001) and IgG-Bp/IgG-Pg>1.5 (76 % vs 60 %, p<0.0001). Conclusion. IgG-Bp, IgG-Es, and IgG-Pg immunoassay could serve as a screening tool to identify population at risk of colorectal and breast cancers.
Breast cancer is the most common cancer and the leading cause of cancer death in woman of childbearing age. Tumor progression depends on the character of stromal-parenchymal interactions. Tumor microenvironment exerts a key influence on tumor progression. Tumor niche is an important element of the tumor microenvironment. According to existing ideas, tumor niche consists on immune cells and bone marrow progenitor cells. The present study describes the parameters of tumor niche in invasive breast carcinoma of no special type (IC-NST), associated with lymph node metastases. The purpose of the study was to investigate the features of tumor niche cell composition in IC-NST. Material and methods. The study included 128 patients with IC-NST (T1–3N0–3M0), who underwent total mastectomy or partial mastectomy with axillary lymph node dissection. The age of the patients ranged from 29 to 90. Histological examination of surgical specimens was carried out in accordance with standard methods. Suspensions of fresh frozen tumor surgical specimens were prepared for the hematopoetic progenitor cells identification. The antibodies against CD34, CD133, CD90, CD11B, CD45, AND CD202 were applied. Results. The study showed that the total number of hematopoietic stem and progenitor cells and macrophage progenitor cells in an amount exceeding 1.24 cells per 100 tumor cells was associated with the risk of developing lymph node metastases and large tumor size. Conclusion. The results obtained may be useful for understanding the role of tumor niche in tumor growth and lymph node metastasis of IC-NST.
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.
Introduction. Thyroid dysfunction is known to be associated with higher risks of cancer development. The purpose of this study was to analyze levels of thyroid axis hormones in the hypothalamus, pituitary gland, thyroid, and blood serum of male and female Balb/c nude mice with B16/F10 melanoma and/or lewis lung carcinoma. Material and methods. Male and female Balb/c nude mice were divided into groups: 1 – intact mice (n=7), 2 – mice with b16/f10 melanoma (n=7), 3 – mice with lewis lung carcinoma (LLC) (n=7), 4 – mice with melanoma and LLC (n=7). Levels of thyroid-stimulating hormone (TSH), triiodothyronine (fT3), and thyroxine (fT4) were measured by ria in homogenates of the hypothalamus, pituitary gland, thyroid and blood serum of all animals, and TH-releasing was measured by ELISA. Statistical processing of results was performed using the Statistica 10.0 program. Results. TH-releasing was reduced in the hypothalamus of all tumor-bearing mice, compared to initial values. TSH levels in the pituitary gland and thyroid were changed only in males with the combination of tumors (increased by 2.8 and 1.5 times, respectively). Levels of free forms of hormones in the thyroid in animals of both genders sharply increased, together with the elevation of TSH in the blood serum and, as a result, the decrease of fТ3 and fТ4 levels. Conclusion. Female and male Balb/c nude mice of the studied groups demonstrated hypothalamic dysfunction manifested by the absence of regulation in the hypothalamus-pituitary-thyroid relationship, and by the hypothyroid status of animals.
ONCOLOGY PRACTICE
Aim. To analyze multimodal treatment outcomes in patients with liver metastases from colorectal cancer, who were treated at multidisciplinary cancer clinic. Material and methods. From 2007 to 2021, 315 colorectal cancer patients with liver metastases underwent liver resections (201, 63.8 %), radiofrequency ablation (RFA) (29, 9.2 %), microwave ablation (MWA) (22, 6.9 %), transarterial chemoembolozation (TACE) in combination with RFA (22, 6.9 %), and TACE + RFA + TACE combination (41, 13.2 %) at the department of liver and pancreas surgery, Moscow Botkin Clinical Hospital. Results. A 90-day mortality rate was 1.9% in 6 patients who underwent liver resection. Postoperative complications after liver resection were observed in 49 patients (24.3 %). The overall 5- and 10-year survival rates after liver resection were 38.8 % and 23.2 %, respectively. The factors of poor prognosis after liver resection were: age over 70 years (p=0.03), localization of the primary tumor in the right half or rectum (p=0.037), three or more metastatic foci in the liver (p=0.01), maximum size of the tumor of more than 5 cm (p=0.021), synchronous colorectal liver metastases (p=0.039), and bilobar colorectal liver metastases (p=0.007). Postoperative complications after RFA, TACE + RFA, TACE + RFA + TACE WERE 5.8 %, 9.1 % and 7.3 %, respectively. In patients with a size of metastases of no more than 3 cm, the 3-year disease-free and overall survival rates after rfa were 45.8 % and 54.2 %, respectively. In patients with a size of metastases from 3 to 5 cm, the 3-year disease-free and overall survival rates after TACE + RFA + TACE were 56.1 % and 63.4 %, respectively. Conclusion. In colorectal cancer patients with liver metastases, multimodal treatment within a multi-disciplinary setting demonstrated significant improvements in their survival.
Purpose of the study: to investigate the composition of the intestinal microbiota and determine the feasibility of using it in diagnosis and prognosis of colorectal cancer (CRC). Material and methods. The study included 75 patients with CC (study group I) and 25 healthy individuals (control group II) who were treated at Chita State Medical Academy from 2017 to 2021. Group I patients underwent surgery and adjuvant chemotherapy. To determine the composition of the intestinal microbiota, biopsy specimens were taken from the tumor tissue and from the visually unchanged colon mucosa after the completion of surgery in the study group and from the visually unchanged colon mucosa during colonoscopy in the control group. Results. The counts of Bifidobacterium spp., E. Coli (typical) in the intestinal microbiota were significantly lower and the concentration of Clostridium spp. Was higher in CRC patients than in healthy individuals. Significant relationships between the counts of Lactobacillus spp., Bifidobacterium spp., Bacteroides spp., E. Coli and the patient’s gender; Lactobacillus spp., Bifidobacterium spp., Staphylococcus spp. (CNS) and the tumor grade; conditionally pathogenic microflora and the form of tumor growth were found. Some combinations of the composition of the intestinal microbiota in CRC patients are predictive factors for the development of postoperative complications (Lactobacillus spp., Bacteroides spp., E. Coli <3.0 CFU/g) and 3-year survival (Lactobacillus spp., Bifidobacterium spp., Bacteroides and E. Coli ≥3.0 CFU/g). Conclusion. The study of the intestinal microbiota makes it possible to differentiate patients with CRC, as well as to predict the risk of postoperative complications and patient survival.
REVIEWS
The purpose of the study was to conduct a systematic literature review of high-technology methods in breast cancer treatment. Material and methods. To select information sources, a global search was used using the Web of Science, Scopus, PubMed, and RSCI databases. The search included the analysis of metadata by keywords, and relevant publications were used for full-text search. The review used 55 publications from 2001 to 2021. Most of the articles were published over the past 7 years. Results. Modern literature data presented in this review prove that long-term studies based on histological and immunological features of tumor development are very important for improving survival in breast cancer. Clinical treatment protocols that were based primarily on the anatomical characteristics of the disease are now switching to the biological mechanisms underlying carcinogenesis. Drugs targeting estrogen receptors play an important role in systemic therapy and make it possible to correct the mechanisms responsible for endocrine resistance. Targeted therapy targeting the HER2 receptor, especially in an antibody-drug conjugate combination, has associated cytotoxic therapy with anti-HER2 antibodies. Modern methods of biological therapy and cell engineering make it possible to develop methods for treating triple-negative breast cancer based on the regulation of the microenvironment, mechanisms of repair, immunosuppression, and the creation of a target from a larger repertoire of both surface and intracellular antigens. Conclusion. Promising strategies based on the use of signaling and metabolic pathways, cell surface molecules, and cell engineering increase the effectiveness of treatment and improve the progression-free and overall survival in breast cancer patients.
Background. Hereditary genetic mutations are a significant risk factor for malignant transformation of cells and cancer development. Hereditary genetic mutations account for 15 to 25 % of all ovarian carcinomas. Purpose of the study: to summarize data on hereditary ovarian malignancies, namely: genetic defects, features of the clinical course, treatment options, and disease prevention. Material and methods. A systemic search was undertaken using PubMed, Medline, Cochrane Library databases for publications from 1999 to 2021. Results. The review describes the main genetic defects and hereditary cancer syndromes predisposing to the development of hereditary malignant ovarian tumors. The features of the clinical course and response to drug therapy have been presented. This article summarizes clinical guidelines of the professional communities (National Comprehensive Cancer Network (NCCN), American Society Of Clinical Oncology (ASCO), The U.S. Preventive Services Task Force, and European Society For Medical Oncology (ESMO). These guidelines contain early detection strategies and approaches to prevent the development of cancers in mutation carriers. Conclusion. Detection of hereditary cancer syndromes is important for patients and their families. Recognizing hereditary predisposition to cancer is important to allow timely surveillance and preventative interventions for both patients and family members.
Aim of the study: a systematic analysis of the modern literature data on the nivolumab monotherapy efficacy in patients with metastatic colorectal cancer (mCRC). Material and methods. The review summarizes the results of clinical studies of the nivolumab efficacy in patients with mCRC between 2012 and 2022. The current approaches to assessing the tumor response in patients treated with immune checkpoint inhibitors are considered, including response patterns and criteria. Results. Data analysis showed that the use of nivolumab in mCRC patients had significant clinical benefits. Nivolumab monotherapy was shown to improve survival in patients with high microsatellite instability (MSI) or deficiencies in mismatch repair (dMMR) that progressed during standard chemotherapy. Numerous clinical studies indicate the atypical response to nivolumab. Traditional response criteria, such as RECIST do not always adequately assess the therapeutic efficacy of nivolumab in patients with mCRC. Conclusion. To improve the efficacy of mCRC treatment, standardized approaches based on the proposed specific criteria for response to immunotherapy, including immune related RECIST, immune RECIST, and immune-modified RECIST must be developed.
Aim of the study: to conduct a systematic analysis of the data available in the modern literature, prognostic factors, and modern methods of rehabilitation of cancer patients after endoprosthetic reconstruction following resection of the lower extremity long bones. Material and methods. We assessed reports of clinical trials published over the past 10 years, which evaluated prognostic factors, rehabilitation programs for cancer patients who underwent endoprosthetic reconstruction following resection of the lower extremity long bones, depending on the location and size of the implant and the age of the patient. The review also evaluated various prognostic factors that affected functional recovery following resection of the lower extremity long bones. Results. Findings that helped in choosing the best option for surgical treatment, thus providing the best quality of life in the postoperative period, were published. Conclusion. Further studies are needed to optimize rehabilitation techniques and develop new algorithms for the treatment of cancer patients who underwent endoprosthetic reconstruction following resection of the lower extremity long bones.
The aim of the study is to study the results of the most significant studies on the forms of tumor cell death and targets in photodynamic therapy (PDT). Material and methods. On the problem, we analyzed the Scopus, WoS, MedLine databases and found 31 sources. Results. PDT is an important tool for studying the pathways leading to the complete devitalization of a malignant tumor. Moreover, subcellular targets in pdt are determined by the properties of photosensitizers (PS). Particularly effective targets are lysosomes and mitochondria, including those for class I PS, photofrin. This explains the effectiveness of photofrin, although it has a weak absorption band in the region of 630 nm with a limited penetration depth into tissues. The development of new PSs with subcellular targets of photofrin, but with an absorption band in the long-wavelength region, is becoming very topical. Such FS are ideal for PDT. Second-generation PSS have already been introduced into clinical practice. The effectiveness of PDT with the use of photoditazine was shown. The mechanisms of action and targets of this PS have been established. The latter include the vessel wall, cytoplasmic membranes, and internal structures of tumor cells. The main type of neoplastic cell death during PDT with photoditazine is direct photocoagulation and ischemic necrosis of the tumor parenchyma due to the destruction of the neoplasm vascular bed. Today, considerable attention is paid to the development of other new PSS, namely, bacteriochlorophyll-α derivatives, which have an intense absorption of radiation in the long-wavelength region of the spectral range. These include the disulfide-bpi conjugate, which contains 2 molecules of dipropoxybacteriopurpurinimide and a cystamine residue, the results of which showed its high efficiency due to the destruction of the tumor vascular bed, the rapid slowdown and/or cessation of cell proliferative activity and their death by necrosis and apoptosis. Rapid progress in studying the mechanisms of action of PDt has shown that autophagy triggering using the lysosomal compartment to degrade and utilize damaged cell organelles and paraptosis associated with defective proteins in the endoplasmic reticulum also play an important role in the elimination of tumor cells. Conclusion. Apoptosis, autophagy, and paraptosis can occur after photodamage to mitochondria, lysosomes, or the endoplasmic reticulum. The balance of cell death pathways is often a determining factor in the effectiveness of PDT.
CASE REPORTS
Background. Stomach cancer is one of the most common cancers worldwide. Long-term treatment outcomes in patients with locally advanced gastric cancer with invasion to adjacent structures are poor. In clinical recommendations of the Ministry of Health of the Russian Federation, it is recommended to treat these patients with perioperative chemotherapy according to the FLOT scheme. The effectiveness of neoadjuvant chemoradiotherapy is studied in many multicenter studies involving randomized clinical trials. Case description. We present a case of a successful treatment of a patient with locally advanced gastric cancer (сT4bN2M0 – IVA stage). The patient received neoadjuvant therapy (2 cycles according to the FLOT scheme) followed by chemoradiotherapy (total dose of 46 Gy with the concurrent chemotherapy with capecitabine and oxaliplatin). Neoadjuvant therapy was well tolerated (grade 1 gastrointestinal and hematological toxicity). The patient underwent distal subtotal resection of the stomach with D2 lymph node dissection and distal subtotal resection of the pancreas with preservation of the spleen. No postoperative complications were observed. Histological examination revealed complete pathological response of the primary tumor, including the area of earlier invasion into the pancreas; metastasis in one lymph node of the small omentum. The patient is alive with no evidence of disease 20 months after surgery. Conclusion. The feasibility of conducting safe multimodal neoadjuvant therapy followed by organ-preserving surgery in a patient with locally advanced gastric cancer (сT4bN2M0) was shown. The effective neoadjuvant therapy resulted in the achievement of complete pathologic response, which is a favorable prognostic factor.
Background. The development of unique immune-related adverse events (irAEs) is a known hallmark of immunotherapy. Generally, such complications occur during the first 3–6 months of immunotherapy, however, the experience with immune checkpoint inhibitors (ICIs) shows that irAEs can also occur after completion of ICI therapy, as well as during other anticancer treatment regimens. Description of the clinical case. We present a clinical case of a patient with metastatic cutaneous melanoma, who had recurrent events of grade 2 immune-mediated diarrhea during the 2ndline of therapy. After completion of the course of immunosuppressive therapy with systemic glucocorticoids, irAE resumed, and mesalazine and budesonide (local steroid) with subsequent dose reduction were prescribed. Maintenance anti-inflammatory therapy and re-induction of targeted therapy with BRAF- and MEK-inhibitors due to the progression of the disease resulted in the reactivation of immune-mediated colitis. The complication was successfully managed by increasing dose of local steroid to full dose. Anticancer therapy was continued at the same regime without recurrent episodes of irAEs. Conclusion. When changing the anticancer treatment regimen, the recurrence of irAEs dictates careful monitoring of toxicity and the importance of timely selection of the optimal treatment algorithm to improve the quality and longevity of cancer patients.
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