Peer-rewieved medical journal. The aim of the edition is to promote scientific achievements of Russian medicine in Russia and abroad. The publication of reviews, lectures, essays by leading Russian and foreign experts in the field of fundamental and ...
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Potential of comprehensive somatic profiling tumor tissue for a personalized approach to treatment selection in various malignant neoplasms
Purpose of the study. Evaluation of the therapy optimization for patients with solid tumors using comprehensive genomic profiling (CGP). Patients and methods. The article presents the results of a study involving patients from the Yamalo-Nenets Autonomous Okrug with malignant neoplasms of various localizations: breast cancer (n = 4), colorectal cancer (n = 3), gastric cancer (n = 1), cervical cancer (n = 1), ovarian cancer (n = 1), and prostate cancer (n = 1). Molecular genetic testing was performed using the Sentis™ Cancer+Discovery Panel (BGI). Biological material included FFPE tumor tissue sections containing >20 % tumor cells. Next-generation sequencing (NGS) parameters were as follows: sequencing depth > 900× for tumor samples and >300× for matched control samples (venous blood); insertion size ~140–210 bp; Q30 > 80 %; target coverage > 90 %. The analysis included 689 genes, microsatellite instability (MSI), tumor mutational burden (TMB), and germline pathogenic variants. Results. Clinically significant somatic biomarkers were identified in 8 of 11 cases (72.7 %), enabling optimization of treatment strategies toward the most effective therapeutic approaches. In 5 of these 8 cases (62.5 %), treatment plan modification included the potential use of off-label therapy following approval by a multidisciplinary tumor board. Germline (inherited) variants were detected in 4 of 11 cases (36.4 %), indicating the need for genetic counseling and evaluation of relatives. Conclusion. The implementation of CGP in clinical practice expands the possibilities for a personalized approach to the treatment of patients with metastatic and progressive malignant neoplasms through the identification of additional potential biomarkers of sensitivity or resistance to targeted anticancer agents and immunotherapy. Further evaluation of CGP effectiveness in a larger patient cohort appears warranted.
Evaluation of the pharmacological efficacy of black crowberry (Empetrum nigrum L.) extract in a rat model of alloxan-induced diabetes
The spectrum of bioactive metabolites identified in the fruits of Empetrum nigrum L. collected in the Kamchatka Territory is of particular interest for the prevention and correction of disorders associated with age-related diseases. Purpose of the study. To investigate the effects of a liquid extract of black crowberry (Empetrum nigrum) fruits on metabolic and oxidative disturbances in rats with alloxan-induced diabetes. Materials and methods. Following the identification of phenolic compounds and saponins in Empetrum nigrum fruits, the biological activities of these compounds were screened using the online Prediction of Activity Spectra for Substances (PASS) software. Experimental studies were conducted to evaluate the hypoglycemic, hepatoprotective, and antioxidant effects of the liquid extract of black crowberry fruits in rats with alloxan-induced diabetes. Assessments were performed using standard biochemical assays and conventional analytical methods on a Mindray BC-480 analyzer. The effects of the Empetrum nigrum liquid extract on antioxidant defense parameters following alloxan administration were evaluated spectrophotometrically by measuring malondialdehyde (MDA) levels and the total antiradical activity index. The comet assay was used to assess the genotoxic effects of alloxan and of the investigated extract. Results. In the rat model of diabetes mellitus, administration of the liquid extract of Empetrum nigrum fruits resulted in a 23.9 % reduction in hyperglycemia (blood glucose level), a 38.7 % decrease in malondialdehyde concentration, and a 38.3 % increase in total antiradical activity compared with the control group (p < 0.05). The comet assay demonstrated the damaging effect of alloxan on liver cells: the number of necrotic and apoptotic cells in the control group was 1.6-fold higher than in the group receiving the black crowberry fruit extract (p < 0.05). Changes in absolute and relative liver weight, as well as biochemical parameters, further confirmed the beneficial effects of Empetrum nigrum L. fruit extract administration. The observed effects were compared with those of the reference compound rutin (a quercetin diglycoside). Conclusion. The present study expands current knowledge regarding the hypoglycemic, hepatoprotective, and antioxidant properties of Empetrum nigrum, highlighting its potential relevance for pharmaceutical development and clinical applications.
Standardized algorithm for developing MRI-based radiomics models for detecting Grade Group ≥ 1 and ≥ 3 prostate cancer: recommendations from a systematic review, meta-analysis, and methodological quality assessment (RQS/METRICS)
Purpose of the study. Based on a synthesis of systematic review data using standard meta-analysis methodology, to evaluate the current state of radiomics model development, analyze sources of methodological heterogeneity, and present a standardized evidence-based algorithm to improve the quality and reproducibility of future studies. Materials and methods. A systematic search was conducted in the PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library databases for studies published between January 2020 and December 2025. Keywords related to radiomics, magnetic resonance imaging (MRI), and prostate cancer (PCa) were used. According to the PICOS criteria, 27 studies involving 5,945 patients were included. Diagnostic performance was assessed using a random-effects meta-analysis, while methodological quality was evaluated independently by two reviewers using the Radiomics Quality Score (RQS) and METRICS instruments. Results. Twenty-seven studies were included. The pooled diagnostic performance of radiomics models was high (AUC = 0.847); however, substantial heterogeneity was observed (I² = 70.32 %). The mean RQS score was 15.2 ± 3.4 (42.3 % of the maximum possible score), while the mean METRICS score was 67.5 ± 9.0 %. Systematic methodological weaknesses were identified, including retrospective study design (96.3 %), lack of external validation (77.8 %), absence of clinical utility assessment (70 %), and failure to report missing-data handling procedures (100 %). Meta-regression demonstrated that a high risk of bias was associated with inflated AUC estimates (p = 0.009). Conclusion. The currently reported high performance of PCa radiomics models should be interpreted with caution because of methodological limitations. The proposed standardized algorithm, incorporating recommendations on prospective study design, validation, data processing, and model development, provides a practical methodological guidance for future research. Its implementation may be key to improving methodological rigor, reproducibility, and the clinical translational value of future studies in this field.
Contemporary diagnostic criteria for adrenocortical neoplasms: from morphology to molecular classification
The diagnosis of adrenocortical tumors has undergone substantial changes in recent years owing to the introduction of reproducible morphological scoring systems combined with validated immunohistochemical and molecular markers. Updates to the WHO Classification of Endocrine and Neuroendocrine Tumours (2025), ICCR datasets, and contemporary clinical guidelines have strengthened requirements for morphological diagnostic standards, immunohistochemical profiling, and interpretation of pathological findings. Purpose of the study. To systematize contemporary morphological, immunohistochemical, and molecular criteria for adrenocortical tumors and to provide a practical algorithm for their stepwise application in pathological diagnosis. Materials and methods. An analytical review of publications from 2021 to 2025 on the pathology and molecular oncoendocrinology of adrenocortical tumors was performed, including the WHO-2025 classification, ICCR datasets, updates to European clinical guidelines, and multicenter studies. Results. Classical morphological criteria, including assessment of mitotic activity, capsular and vascular invasion, and cytological atypia, remain fundamental for the diagnosis of adrenocortical tumors. The review systematizes the principal morphological tools, including the Weiss criteria and their modifications, the Helsinki score, and the reticulin algorithm. Diagnostic features of oncocytic (Lin–Weiss–Bisceglia), myxoid, and pediatric variants of adrenocortical tumors are discussed. Current evidence regarding the role of SF-1 as a highly specific marker of adrenocortical origin is summarized, together with the significance of a high Ki-67 index as one of the most important diagnostic and prognostic indicators of malignancy, taking into account established threshold values and strict counting methodology. Increased IGF2 expression is also highlighted as an additional marker of malignancy. Furthermore, the review provides a comprehensive overview of major molecular drivers, including TP53, CTNNB1/β-catenin, ZNRF3, and TERT-promoter alterations, as well as DNA methylation signatures and microRNA profiles (miR-483). The contribution of single-cell and spatial transcriptomics and emerging noninvasive biomarkers, including steroid metabolomics and liquid biopsy, is also discussed. Conclusion. The transition toward integrated morphomolecular stratification improves diagnostic and prognostic accuracy in adrenocortical tumors, enhances the comparability of pathology reports, and facilitates patient selection for surveillance and treatment.
Impact of pressurized intraperitoneal aerosol chemotherapy on adhesion formation in the combined treatment of ovarian cancer with peritoneal carcinomatosis
Purpose of the study. To assess the dynamics of the Peritoneal Adhesion Index (PAI) and the number of involved anatomical regions of the abdominal cavity in patients with ovarian cancer and peritoneal carcinomatosis during consecutive sessions of pressurized intraperitoneal aerosol chemotherapy (PIPAC). Patients and methods. A single-center observational study with intraoperative assessment of adhesive status was performed in 87 patients. PAI and the number of involved abdominal regions were determined during three PIPAC sessions and at delayed diagnostic laparoscopy. Available completed paired observations were used for interval comparisons. The primary endpoint was the change in total PAI; secondary endpoints were changes in the number of involved regions and the overall direction of changes by the time of delayed laparoscopy. The statistical significance of paired changes was assessed using the sign test. Results. Between the 1st and 2nd PIPAC sessions, a decrease in PAI was recorded in 57 patients (65.5 %), no change in 24 (27.6 %), and an increase in 6 (6.9 %); the mean change was – 2.7 points (p < 0.0001). Between the 2nd and 3rd PIPAC sessions, a decrease in PAI was observed in 35 patients (38.9 %), no change in 53 (58.9 %), and an increase in 2 (2.2 %); the mean change was 0.89 points (p < 0.0001). Between the 3rd PIPAC session and delayed laparoscopy, a decrease in PAI was observed in 14 patients (16.1 %), no change in 70 (80.5 %), and an increase in 3 (3.4 %); the mean change was 0.10 points (p = 0.006). Overall, a decrease in PAI from baseline to delayed laparoscopy was recorded in 56 patients (64.4 %), no change in 22 (25.3 %), and an increase in 9 (10.3 %); the mean cumulative change was 3.7 points (p < 0.0001). A similar pattern was observed for the number of involved regions: an overall decrease was recorded in 54 patients (62.1 %), no change in 24 (27.6 %), and an increase in 9 (10.3 %); the mean cumulative change was 1.32 points (p < 0.0001). Conclusion. The sequential use of PIPAC was associated with a reduction in the severity and extent of abdominal adhesions, indicating a favorable safety profile of PIPAC and the technical feasibility of repeated laparoscopic procedures.
Planimetric wound assessment using neural network technology
In clinical practice, one of the key methods for monitoring the effectiveness of soft tissue wound treatment is the assessment of wound surface area. Neural network technologies represent a promising approach for calculating wound surface area, identifying signs of wound healing progression, and planning personalized treatment according to clinical dynamics. Purpose of the study. To analyze the results of wound surface area measurements obtained using the WoundVision software. Materials and methods. The study was conducted in three stages: bench testing using schematic wounds and wound models, experimental testing in laboratory animals, and clinical evaluation in patients with trophic ulcers. The accuracy of wound surface area assessment was compared using the L. N. Popova method, ImageJ, UniversalDesktopRuler, and WoundVision computer software, as well as the ImitoWound mobile application. Results. The accuracy of wound area calculation was found to depend on contour shape and surface curvature. ImageJ and UniversalDesktopRuler systematically underestimated measurements, with an average accuracy of 80–88 %. The ImitoWound application demonstrated stable results with an average accuracy of 92 %, although its performance decreased on curved surfaces. Due to the implementation of neural network technologies and 3D scanning, the WoundVision software demonstrated the best results across all study groups. When using WoundVision, the mean accuracy of wound area measurements was 98.27 ± 0.65 % for schematic wounds, 99.19 ± 0.49 % for wound models, 98.52 ± 4.17 % for wounds in laboratory animals, and 98.52 ± 4.17 % for trophic ulcers in patients. Conclusion. The developed WoundVision software demonstrated the highest accuracy among the evaluated methods. However, several limitations remain, including the need for a specialized camera. Nevertheless, the L. N. Popova method remains the most accurate currently available technique, although it is labor-intensive because of the time required for its implementation and its practical limitations.
Treatment of HER2/neu-positive breast cancer with brain metastases: a clinical case
Breast cancer (BC) remains one of the most common oncological diseases among women worldwide, ranking among the leading causes of both cancer incidence and mortality. The main cause of unfavorable outcomes in BC is distant metastasis. The brain is one of the most frequent sites of distant metastatic spread, which significantly complicates treatment and worsens prognosis. This is the blood–brain barrier, which limits the penetration of many chemotherapeutic agents, as well as the aggressive biology of the tumor. This article presents a clinical case of effective use of modern targeted agents in a patient with diagnosed breast cancer who initially had an unfavorable prognosis and disease progression after previous therapy. Particular attention is paid to treatment strategy selection and the use of contemporary targeted therapies that demonstrated clinical efficacy. The described case illustrates the potential of a personalized approach in the treatment of this category of patients, including the possibility of disease control and improvement of clinical outcomes. The analysis of the presented clinical case indicates the need for further development of systemic maintenance therapy, as well as broader implementation of targeted and combined treatment approaches. Individualization of therapeutic strategies taking into account tumor biological characteristics and prior treatment history may contribute to improved treatment efficacy and quality of life.
Risk of disease progression in pediatric lymphatic malformations: predictors and a clinical risk score
Lymphatic malformations (LMs) in children are characterized by a prolonged and fluctuating clinical course with a risk of continued growth or recurrent enlargement after treatment. Identification of independent predictors and development of a clinically applicable risk score may improve treatment planning and long-term follow-up strategies. Purpose of the study. To identify independent clinical and anatomical predictors of continued growth or recurrent enlargement of lymphatic malformations in children after initiation of surgical treatment using multivariable analysis. Patients and methods. A retrospective single-center cohort study was conducted between 2012 and 2022. A total of 115 patients aged 17 years or younger were included who underwent surgical treatment (including extensive resection procedures), sclerotherapy, or combined treatment. The primary endpoint was the first episode of continued growth or recurrent enlargement of LM, defined predominantly by contrast-enhanced magnetic resonance imaging findings. Receiver operating characteristic analysis was used to determine the optimal lesion volume threshold. Multivariable logistic regression with bootstrap validation and time-to-event analysis using Kaplan–Meier and Cox methods were performed. Results. The median follow-up after the index intervention was 11.0 (3.2–27.0) months. The event occurred in 22 of 115 patients (19.1 %). At the last follow-up visit, a ≥50 % reduction in lesion volume or complete response was observed in 95 of 115 patients (82.6 %), a <50 % reduction in 15 of 115 patients (13.0 %), and ongoing growth in 5 of 115 patients (4.3 %). Independent risk factors included prenatal or neonatal onset (OR 4.08; 95 % CI 1.10–15.05; p = 0.035), preoperative lesion volume ≥ 90 cm³ (OR 4.06; 95 % CI 1.09–15.15; p = 0.037), and previous surgery outside a referral center (OR 5.93; 95 % CI 1.73–20.36; p = 0.005). Aggressive anatomical spread demonstrated a trend toward increased risk (OR 2.82; p = 0.092). Model discrimination was high (AUC 0.812; 95 % CI 0.708–0.916) and remained stable after internal validation (AUC_0.632+ = 0.812). The additive score stratified the risk of the event as 6.0 % (95 % CI 1.9–17.4) for patients with ≤1 point, 10.3 % (95 % CI 3.2–28.7) for those with 2 points, and 44.4 % (95 % CI 28.8–61.2) for those with ≥ 3 points. Median event-free survival was 65.2 months. No significant differences were observed between treatment approaches (log-rank p = 0.699). Conclusion. In this cohort, the risk of continued growth in pediatric lymphatic malformations was primarily associated with early disease onset, baseline lesion volume, and previous surgery outside a referral center, whereas extensive anatomical involvement demonstrated a trend toward increased risk. The proposed risk stratification score may support individualized follow-up and treatment planning; however, external validation is required.
The copy number variations of genes regulating mitochondrial function in benign and malignant uterine body neoplasms
Purpose of the study. To study changes in the copy number of genes whose products are involved in maintaining the structure and function of mitochondria in tissues of benign neoplasms and endometrioid adenocarcinoma (EA) of the uterine body of varying degrees of differentiation. Materials and methods. The study utilized tumor tissue and normal uterine tissue from 42 patients with endometrioid adenocarcinoma (EA) and 15 patients with uterine fibroids. The tumor burden in the EA patients was between stages Ia and Ib, and neoadjuvant treatment was not administered. DNA was isolated from tumor and normal uterine tissue fragments using phenol-chloroform extraction, and relative gene copy numbers were determined using real-time PCR (real-time qPCR). Statistical analysis was performed using the Mann-Whitney U-test with a Bonferroni correction. Results. In patients with EA G1, a decrease in the copy number of nuclear and mitochondrial genes was observed (MT-CO1 = 0.5, mtTFB = 0.4, mtSSB = 0.6, MT-RNR2 = 0.3, NRF1 = 0.4) (p < 0.005) and an increase in the copy number of MGME1 (2.4) (p < 0.005). In patients with EA G2, a picture similar to G1 is observed: a decrease in the copy number of the genes MT-CO1; mtTFB, MT-RNR2 and NRF1 (p < 0.005), except for mtSSB. An increase in the copy number of MGME1 (3.1) and POLRMT (1.8) (p < 0.005) was also recorded. In patients with EA G3, the most pronounced decrease in the copy number of mtSSB and MT-RNR2 by 5.0 times relative to normal tissue was found, as well as a decrease in the copy number of MGME1 by 3.3 times, which is the opposite of the results in G1/G2. Conclusion. Significant differences in the copy number of genes involved in mitochondrial function were identified between benign uterine tissues and endometrioid adenocarcinoma. The most prominent alterations included reduced copy numbers of key mitochondrial genes (MT-CO1 and MT-RNR2), the nuclear gene mtSSB, and aberrant MGME1 copy number changes in tumor tissues. These findings provide new insights into the molecular mechanisms underlying endometrioid adenocarcinoma development and may contribute to the identification of potential diagnostic and prognostic biomarkers.
Features of steroid hormone and receptor content in the mitochondria of endometrial adenocarcinoma according to tumor differentiation grade and the presence of type 2 diabetes mellitus
Mitochondria play a key role in cellular metabolism, steroid hormone synthesis, and the regulation of redox homeostasis. However, the role of mitochondrial steroidogenesis in the progression of endometrial adenocarcinoma (EA), particularly in the presence of type 2 diabetes mellitus (T2DM), remains poorly understood. Purpose of the study. To determine the concentrations of steroid hormones and their receptors in the mitochondrial fraction of G1–G3 endometrial adenocarcinoma tissue compared with intact endometrium and to evaluate the modifying effect of type 2 diabetes mellitus on these parameters. Patients and methods. Mitochondria were isolated by differential centrifugation from tumor tissue obtained from 92 patients with endometrial adenocarcinoma (G1–G3) and from morphologically normal endometrium (control group). Standard enzyme-linked immunosorbent assay (ELISA) kits were used to determine the concentrations of estradiol (E2), estriol (E3), estrone (E1) and their receptors (ERα, ERβ), testosterone (T) and the androgen receptor (AR), progesterone (P4) and the progesterone receptor (PR), as well as cortisol and cholesterol. Statistical analysis was performed using Statistica 10 software. Results. In the mitochondria of G1–G2 endometrial adenocarcinomas, the estradiol level was approximately twofold higher than in the control group, whereas G3 tumors demonstrated an approximately twofold increase in estriol concentration. Testosterone and cortisol levels were elevated in the mitochondria of all tumors by 1.6-fold and more than twofold, respectively. Progesterone content was increased by 2.3–3.8-fold in the mitochondria of G1–G2 tumors but decreased by 4.3–5.9-fold in comparison with the control mitochondria. The levels of androgen and estrogen receptors were elevated in the mitochondria of all tumors, whereas the ERα/ERβ ratio decreased by 1.7–3.6-fold. Progesterone receptor levels were increased in G1–G2 mitochondria only in patients with T2DM, whereas in G3 tumors they were elevated regardless of T2DM status. Type 2 diabetes mellitus was associated with cholesterol accumulation in the mitochondria of all tumors. Conclusion. Regardless of tumor differentiation grade and the presence of type 2 diabetes mellitus, endometrial adenocarcinoma mitochondria are characterized by increased levels of testosterone, cortisol, and sex hormone receptors, reflecting profound metabolic reprogramming of these organelles. Estradiol predominates in G1–G2 tumors, whereas estriol is the dominant estrogen in G3 tumors, which may contribute to increased tumor aggressiveness. Type 2 diabetes mellitus is associated with mitochondrial cholesterol accumulation, which may partly explain the more severe clinical course of endometrial adenocarcinoma in these patients.
Features of mitochondrial hormone and receptor levels in aggressive endometrial cancer subtypes
Serous endometrial carcinoma (SEC) and clear cell endometrial carcinoma (CCEC) are among the most aggressive subtypes of endometrial cancer (EC), characterized by a high risk of recurrence and metastasis. Mitochondria play a key role in steroidogenesis and cellular metabolism; however, their contribution to hormonal and metabolic tumor adaptation in rare forms of EC remains poorly understood. Purpose of the study. To comprehensively assess the levels of sex hormones, their receptors, cortisol, and glutathione in mitochondria isolated from SEC and CCEC tissues. Patients and methods. This prospective study included 41 patients with rare forms of EC. Mitochondria were isolated from tumor tissues – 21 SEC and 20 CCEC. The control group was composed of 20 samples of endometrium unaffected by tumour. Concentrations of estrone, estradiol, estriol, testosterone, progesterone, estrogen receptors (REα, REβ), androgen receptors, progesterone receptors (RP4), cortisol, cholesterol, and glutathione were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistica 10.0 software. Results. In mitochondria obtained from SEC and CCEC, compared with tumor-free endometrial mitochondria, levels of testosterone and progesterone were increased by an average of 1.5‑fold, estriol by 1.8‑fold and 2.2‑fold, REβ by 3.5‑fold and 1.8‑fold, RP4 by 2.4‑fold and 5.2‑fold, and the REβ/REα ratio by 2.2‑fold and 1.9‑fold, respectively. Estradiol, REα, and androgen receptor levels exceeded control values only in SEC mitochondria, by 2.0‑fold, 1.8‑fold, and 2.2‑fold, respectively. Cortisol and cholesterol concentrations in mitochondria from rare endometrial cancer subtypes were 1.9–2.5‑fold higher than in tumor-free endometrial mitochondria, while glutathione levels were increased by 1.9–2.4‑fold. Conclusion. SEC and CCEC are characterized by the formation of a unique mitochondrial hormonal microenvironment with estriol predominance and a high REβ/REα ratio, which may mediate suppression of apoptosis and enhanced proliferation. Differences in receptor profiles indicate distinct mechanisms of hormonal signaling, potentially determining specific features of the clinical course of each tumor subtype. Accumulation of cholesterol and cortisol in the context of elevated glutathione levels indicates metabolic reprogramming aimed at sustaining steroidogenesis and resistance to oxidative stress and apoptosis.
Use of laparoscopic ultrasound in emergency surgery for cholelithiasis
Laparoscopic ultrasound provides a wide range of intraoperative diagnostic capabilities during endoscopic abdominal procedures. The absence of key limitations inherent to radiographic cholangiography makes laparoscopic ultrasound a potential alternative method for diagnosing complicated forms of cholelithiasis. Purpose of the study. To summarize current evidence on the use of laparoscopic ultrasound during surgical interventions for biliary tract diseases. Materials and methods. A literature review was conducted of publications from 1997 to 2024 indexed in PubMed and Google Scholar using the following keywords: “laparoscopic ultrasound,” “intraoperative ultrasound,” “radiographic cholangiography,” “acute cholecystitis,” “laparoscopic cholecystectomy,” and “choledocholithiasis”. Results. Analysis of the selected studies highlights the specific ultrasound semiotics of the biliary tract. Comprehensive visualization and interpretation of the structures within the hepatoduodenal ligament contribute to safer surgical procedures and reduce the rate of unplanned conversions. Laparoscopic ultrasound demonstrates high diagnostic accuracy in detecting choledocholithiasis, comparable to radiographic cholangiography. However, only a limited proportion of surgeons routinely incorporate laparoscopic ultrasound into their practice. Conclusion. Laparoscopic ultrasound represents a viable alternative to radiographic cholangiography. Its advantages include the possibility of repeated intraoperative use, reduced risk of bile duct injury, and shortened overall diagnostic time.
Neutrophils in cancer and sepsis: shared mechanisms of immune dysregulation
Neutrophils, the predominant leukocytes of the innate immune system, are increasingly recognized as potential participants in processes that either promote or suppress tumor development, depending on the tumor's biological characteristics. Purpose of the study. This narrative review aims to analyze and summarize current knowledge on the functional plasticity and heterogeneity of neutrophils, as well as their dual role in the pathogenesis of cancer and sepsis. Particular attention is given to shared mechanisms of neutrophil dysregulation in these conditions and to the prospects for developing targeted therapeutic strategies. Materials and methods. A selective literature search was conducted in the PubMed, eLibrary.ru, and Scopus databases covering the past 15 years using the following keywords: “neutrophils”, “cancer”, “sepsis”, “neutrophils in cancer and sepsis”, “immune dysregulation in cancer and sepsis”, “neutrophil plasticity in tumor and infection”, “immunotherapy and sepsis in cancer patients”, “oxidative stress in neutrophils”, “neutrophil–lymphocyte ratio”, and “sepsis-induced tumor growth”. Publications were selected based on their scientific significance, relevance to the topic, and compliance with contemporary evidence-based medicine standards. Results. The analysis revealed the dual role of neutrophils in cancer and their complex interactions within the tumor microenvironment. The review discusses two neutrophil subtypes, N1 and N2, which exert opposing effects on tumor biology. It also examines the role of neutrophils in the formation and function of neutrophil extracellular traps (NETs), which contribute to cancer progression through their involvement in inflammation, angiogenesis, and metastasis. In addition, the review highlights shared mechanisms of neutrophil involvement in cancer progression and sepsis in oncology patients, with particular emphasis on activated neutrophils and NET formation. Conclusion. Integrating current knowledge on neutrophil involvement in cancer progression and sepsis in oncology patients may guide future research toward the development of more precise and effective therapeutic strategies for cancer complicated by sepsis, ultimately improving patient outcomes.
The role of extracellular matrix remodeling markers (MMP-2 and TIMP-1) in predicting chronic kidney disease progression after partial laparoscopic nephrectomy
Partial nephrectomy is the treatment of choice for localized renal cell carcinoma. Following organ-sparing surgery, extracellular matrix remodeling processes develop in renal tissue and are regulated by the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Conventional assessment of renal function based on serum creatinine levels does not reflect local tissue remodeling processes. Purpose of the study. To evaluate the dynamics and interrelationship of TIMP‑1, MMP‑2, and serum creatinine levels in patients with renal cell carcinoma after partial laparoscopic nephrectomy, and to determine their association with progression of chronic kidney disease (CKD). Patients and methods. This prospective study included 633 patients with localized renal cell carcinoma who underwent partial laparoscopic nephrectomy or tumor enucleation. TIMP‑1 and MMP‑2 levels were measured using enzyme-linked immunosorbent assay (ELISA), and serum creatinine was determined by a kinetic colorimetric method preoperatively, on postoperative days 7 and 30, and at 12 and 24 months. Analysis of CKD progression was performed in a subgroup of patients with complete 24‑month follow-up (n = 119). CKD progression was defined as transition to a higher CKD stage. Correlation analysis, subgroup analysis, and multivariable logistic regression modeling with ROC analysis were performed. Results. A transient increase in TIMP‑1 levels was observed by postoperative day 7. MMP‑2 demonstrated marked variability, with a peak in median values at 1 month (p < 0.05). A weak positive correlation between TIMP‑1 and MMP‑2 was detected on day 7 (r = 0.10; p = 0.012). No significant association was found between these markers and serum creatinine levels (p > 0.05). At 24 months, higher TIMP‑1 levels were independently associated with CKD progression (OR = 3.6; 95 % CI 1.5–8.7; p = 0.004). The model demonstrated good predictive performance with an AUC of 0.81. Conclusion. MMP‑2 and TIMP‑1 reflect specific features of postoperative extracellular matrix remodeling and do not correlate with serum creatinine dynamics. Elevated TIMP‑1 levels in the late postoperative period are associated with CKD progression and demonstrate prognostic potential.
Clinical observation of rib resection using a patient-specific 3D implant in the surgical treatment of chondrosarcoma
To date, surgical treatment remains the main therapeutic option for patients with chest wall tumors. Given the importance of preserving the structural integrity of the thoracic cage during extensive resections, the choice of reconstruction method for post-resection chest wall defects remains one of the key challenges in thoracic surgery. This clinical case report presents the treatment outcomes of a 64‑year-old female patient diagnosed with primary multiple metachronous malignancies who underwent rib resection followed by alloplastic reconstruction using a patient-specific 3D implant made of a nickel–titanium alloy. The implant was designed based on an individualized model and featured a double-locking mechanism using clamp-type fixation. At the 12‑month follow-up, no evidence of tumor recurrence was detected; the implant remained stable, the physiological volume of the thoracic cavity was preserved, and no signs of paradoxical respiration were observed. The proposed patient-specific modular 3D implant is convenient for intraoperative placement, allowing minimization of the risk of bleeding and infectious complications, as well as reduction of operative time. The technique of sternal and rib reconstruction using a patient-specific modular 3D implant is safe and effective and can be widely implemented in clinical practice.
Intraoperative indocyanine green lymphography during lymph node dissection in patients with colorectal cancer liver metastases
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text-transform: unset; text-underline-offset: unset; text-underline-position: unset; text-wrap: unset; timeline-scope: unset; touch-action: unset; transform: unset; transform-box: unset; transform-origin: unset; transform-style: unset; transition: unset; translate: unset; user-select: unset; vector-effect: unset; vertical-align: unset; view-timeline: unset; view-transition-class: unset; view-transition-group: unset; view-transition-name: unset; visibility: unset; border-spacing: unset; -webkit-box-align: unset; -webkit-box-decoration-break: unset; -webkit-box-direction: unset; -webkit-box-flex: unset; -webkit-box-ordinal-group: unset; -webkit-box-orient: unset; -webkit-box-pack: unset; -webkit-box-reflect: unset; -webkit-line-break: unset; -webkit-line-clamp: unset; -webkit-mask-box-image: unset; -webkit-rtl-ordering: unset; -webkit-ruby-position: unset; -webkit-tap-highlight-color: unset; -webkit-text-combine: unset; -webkit-text-decorations-in-effect: unset; -webkit-text-fill-color: unset; -webkit-text-security: unset; -webkit-text-stroke: unset; -webkit-user-drag: unset; white-space-collapse: unset; widows: unset; width: unset; will-change: unset; word-break: unset; word-spacing: unset; x: unset; y: unset; z-index: unset;">Purpose of the study. To evaluate the diagnostic performance of intraoperative fluorescence lymphography in patients with colorectal liver metastases (CLM). Patients and methods. The study included 55 patients with CLM who underwent intraoperative fluorescence lymphography with indocyanine green (ICG) during laparotomy to guide hepatic hilum lymph node dissection (LND) and liver resection. The first three fluorescent lymph nodes (LNs), defined as sentinel lymph nodes (SLNs), were identified within 30–45 minutes after peritumoral ICG injection. LND was performed with excision and labeling of SLNs and all fluorescent LNs detected during the observation period, as well as lymph nodes from stations 12, 13, and 8, regardless of fluorescence. Liver resection was subsequently performed. Results. In six of 55 patients (10.9 %), no SLNs were visualized. These patients underwent LND with removal of lymph nodes from stations 12, 8, and 13; histopathological examination revealed no LN metastases in this subgroup. In the remaining patients (89.1 %, n = 49), SLN fluorescence was observed. Histopathological analysis demonstrated lymphogenous metastases in 11 of 55 patients (20.0 %). In four of these 11 patients (36.3 %), selective LND based solely on preoperative imaging and intraoperative assessment would have failed to identify and remove metastatic LNs. The sensitivity of ICG lymphography was 100 %: in all 11 patients with nodal metastases, at least one SLN (SLN No1, No2, or No3) was involved. In two cases (18.2 %), metastatic involvement was detected only in SLN No3, with SLN No1 and SLN No2 being negative. Only one of the 11 patients (9.1 %) had additional metastatic LNs beyond the SLN basin; in this patient, all three SLNs were metastatic. Conclusion. Hepatic hilum LN metastases were detected in one in five patients with CLM. Reliable preoperative or intraoperative identification of metastatic hilar LNs remains challenging. ICG-guided SLN mapping enables more precise lymph node dissection. Further studies are required to determine whether this approach improves long-term oncological outcomes after liver resection for CLM.
Surgical complications after oncoplastic resections in patients with breast cancer
Purpose of the study. To analyze published data on the incidence and characteristics of surgical complications following oncoplastic resections in patients with breast cancer (BC). Materials and methods. The results of 27 domestic and international publications published between 2013 and 2025 were analyzed. Relevant sources were searched in the PubMed, Cochrane Library, and eLibrary databases. Results. According to the literature, the most common complications after oncoplastic resections in patients with breast cancer included wound dehiscence (3–9 %), seroma/hematoma (2–5 0 %), liponecrosis (1–5 %), infectious complications (4–20 %), and ischemic complications (0.8–2.5 %). The frequency and nature of surgical complications following oncoplastic and reconstructive procedures have been investigated in numerous studies. It is evident that the development of complications after reconstructive procedures may negatively affect patients’ quality of life. A thorough analysis of the causes of complications and strategies for their management allows surgeons to objectively assess the advantages and limitations of different techniques when planning the extent of surgical treatment. Conclusion. The literature review indicates that various oncoplastic resection techniques, despite the potential occurrence of complications, are not associated with a statistically significant deterioration in aesthetic outcomes or oncological treatment results. However, careful patient selection is required to minimize the risk of surgical complications when choosing among different oncoplastic resection techniques.
Immediate efficacy and safety profile of a de-escalated neoadjuvant THP regimen in early HER2-positive breast cancer: preliminary results of a prospective study
De-escalation of neoadjuvant therapy for HER2‑positive breast cancer remains one of the key trends in modern oncology. The search for treatment regimens that reduce toxicity without compromising antitumor efficacy remains a clinically relevant challenge. Purpose of the study. To evaluate the immediate efficacy (pathological complete response rate) and safety profile of a de-escalated 12‑week neoadjuvant THP regimen (paclitaxel, trastuzumab, pertuzumab) in patients with early HER2‑positive breast cancer. Patients and methods. A prospective single-center study conducted at the P. A. Hertsen Moscow Oncology Research Institute included 55 patients with verified stage IIA–IIB HER2‑positive breast cancer. All patients received THP neoadjuvant therapy consisting of 12 weekly infusions of paclitaxel (80 mg/m²) combined with dual HER2 blockade (trastuzumab + pertuzumab, 4 cycles). The primary endpoint was the pathological complete response (pCR) rate (ypT0/is ypN0). Secondary endpoints included the toxicity profile and the rate of breast-conserving surgery. Results. A pathological complete response was achieved in 34 (61.8 %; 95 % CI 48.6–73.5) of 55 patients in the overall cohort. Subgroup analysis revealed a statistically significant association between efficacy and biological subtype: the pCR rate was 76.2 % in non-luminal HER2‑positive cancer compared to 52.9 % in the luminal subtype (p = 0.04). High tumor grade (G3, 87.5 %) and high Ki‑67 index (>30 %, 73.2 %) were also significant factors associated with a high probability of pCR. The rate of lymph node metastasis eradication in patients with initial cN1 status was 85.0 %. The safety profile was favorable: no cases of febrile neutropenia or grade 3–4 toxicity were recorded, and no dose reductions were required. Conclusion. The de-escalated 12‑week THP regimen demonstrates high immediate efficacy, comparable to standard platinum-containing regimens, with an exceptionally favorable safety profile. The results support the use of this regimen as a de-escalation option, particularly for patients with non-luminal tumor subtypes and those at high risk of toxicity from standard treatment regimens.
Magnetic resonance imaging in the diagnosis of cerebellar-type multiple system atrophy
Cerebellar-type multiple system atrophy (MSA-C) presents significant challenges for early diagnosis due to the absence of specific biomarkers and its clinical similarity to other forms of ataxia. The presented clinical case highlights the importance of dynamic monitoring of magnetic resonance imaging (MRI) changes for confirming the diagnosis of MSA-C and demonstrates the characteristic temporal evolution of key neuroimaging markers. A clinical observation of a 47‑year-old patient with progressive cerebellar ataxia and autonomic failure (orthostatic hypotension, urinary incontinence) consistent with established diagnostic criteria for MSA-C is presented. Brain MRI findings obtained in follow-up with a 7‑month interval are of particular value. First detection of the highly specific “hot cross bun” sign for MSA-C – a cross-shaped area of hyperintense signal in the central pons. Progressive thinning of the middle cerebellar peduncles (by 3 mm), cerebellar vermis atrophy (by 2 mm), and enlargement of the fourth ventricle and pontine cisterns were also documented. These changes objectively correlated with the progression of cerebellar clinical symptoms in the patient. The findings of this clinical case indicate that dynamic MRI evaluation is an indispensable method in the diagnosis of MSA-C. The appearance of the pathognomonic “hot cross bun” sign and quantitatively measurable progression of atrophy in specific posterior fossa structures (the cerebellum, middle cerebellar peduncles, and pons) over a short time interval represent highly specific radiological criteria that allow reliable differentiation of MSA-C from hereditary ataxias even in the absence of definitive biomarkers. Early and sequential MRI with assessment of imaging changes over time significantly improves the accuracy of antemortem diagnosis of this severe neurodegenerative disease.
Regulatory role of growth factors during N-acetylcysteine administration in the model of radiation-induced pancreatic injury
Purpose of the study. To evaluate the roles of the growth factors IGF‑1, TGF-β, and VEGF-A in regulating delayed regenerative mechanisms induced by N-acetylcysteine (NAC) administered prior to local pancreatic irradiation with electrons at a total dose of 30 Gy. Materials and methods. An experimental study was conducted on 60 male Wistar rats, which were divided into four groups: Group 1 (control, n = 10): rats received an intraperitoneal injection of NaCl solution without local electron irradiation; Group 2 (n = 20): intraperitoneal administration of 0.9 % NaCl solution prior to local electron irradiation in a fractionated mode with a total focal dose (TFD) of 30 Gy; Group 3 (n = 20): intraperitoneal administration of N-AC at a dose of 120 mg/kg prior to local electron irradiation in a fractionated mode with a TFD of 30 Gy; Group 4 (n = 10): intraperitoneal administration of N-AC at a dose of 120 mg/kg without local electron irradiation. Thirty days after irradiation, blood levels of glucose, insulin, and amylase were measured. Histological analysis of pancreatic islet architecture, the degree of perivascular fibrosis (Masson’s trichrome staining), and the expression of IGF‑1, TGF-β, and VEGF-A were assessed by immunohistochemistry through counting positively stained cells. Results. Irradiation resulted in elevated blood glucose and amylase levels and decreased insulin levels. Signs of radiation-induced pancreatic injury were accompanied by reduced expression of IGF‑1 and VEGF-A in the islets by 39 % and 56 %, respectively, while the proportion of TGF-β-positive cells exceeded the control values by 3.4‑fold. Pre-irradiation administration of NAC partially preserved biochemical parameters within the normal range, suppressed TGF-β expression, and maintained the numbers of IGF‑1- and VEGF-A-positive endocrine cells at levels 2.5 and 3 times higher than those in the irradiation-only group, respectively. Conclusion. Pre-irradiation administration of NAC exerts a modulatory effect on the expression of growth factors IGF‑1, TGF-β, and VEGF-A in the late period following local electron irradiation of the pancreas, promoting restoration of the organ’s structural integrity and endocrine function. The obtained data suggest that N-AC is a promising agent for the prevention of delayed post-radiation complications, including fibrosis as well as metabolic and secretory insufficiency of the pancreatic islets.