HERALD of North-Western State Medical University named after I.I. Mechnikov

Radiation therapy is one of the most common cancer treatment methods, with approximately 50–60% of cancer patients receiving it. Despite the outstanding advances in the field of its application, especially once technology is concerned, significant obstacles still need to be overcome. The main problems of radiation therapy include tumor resistance and damage to healthy tissues, which leads to negative consequences and inadequate tumor control. Manipulations with the microRNA family is considered to be a promising approach for overcoming these limitations.

The purpose of the review is to analyze the literature data on the role of microRNAs in the regulation of resistance to radiation therapy in human tumors, as well as to evaluate the possibility of manipulations with microRNAs to overcome radioresistance. The evaluation of the articles was carried out in accordance with PRISMA guidelines. The search retrieved 2153 publications. The search queries included the following keywords and their combinations: “microRNA”, “cancer”, “oncological diseases”, “malignant neoplasms”, “radiation therapy”, “radioresistance”. The analysis of the literature data shows that microRNAs will play an important role in radiation oncology in the future. The use of microRNAs is likely to be the basis for the development of specialized therapies that will increase radiosensitivity, as well as for predicting the response to radiation therapy. Early studies have shown that microRNAs can be used as biomarkers for predicting and monitoring therapy, providing a more accurate and personalized approach to patient management.

This article provides a comprehensive review of current standards and promising trends in radiation therapy for triple-negative breast cancer. The latest advancements in the diagnosis and treatment of this aggressive cancer type are examined, including the implementation of advanced radiation therapy techniques such as stereotactic radiotherapy, intensity-modulated radiation therapy, and intraoperative radiation therapy. Particular attention is given to optimizing treatment regimens, reducing side effects, and improving patients’ quality of life. Various approaches to combining radiation therapy with chemotherapy, immunotherapy, and targeted therapy are discussed, along with the prospects of personalized treatment based on the molecular and genetic characteristics of tumors. The results of recent clinical trials aimed at identifying the most effective treatment strategies are analyzed. The importance of a multidisciplinary approach involving oncologists, radiologists, and other specialists is emphasized. Additionally, the impact of emerging technologies and personalized medicine on radiation therapy development is explored, including the use of artificial intelligence and biomarkers for individualized treatment selection. Furthermore, issues related to radiobiology, mechanisms of tumor cell radioresistance, and potential strategies to overcome them are discussed to enhance treatment effectiveness and improve patient outcomes in triple-negative breast cancer.

BACKGROUND: Enteroatmospheric fistulas account for 1–2% of all postoperative complications, with mortality ranging from 14–25%. Moreover, in more than 60% of cases they occur in people of working age, which determines the social significance of the problem.

AIM: To present the results of management patients with enteroatmospheric fistulas applying two-stage protocol.

METHODS: The article presents the experience of treating 169 patients with enteroatmospheric fistulas by a multidisciplinary team over the past decade at the Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine. The treatment was carried out according to a two-stage differentiated protocol developed on the basis of the SOWATS algorithm. The selection of nutritional and metabolic therapy and local management of laparostomy wounds was carried out taking into account the possibility of fistuloclysis and the type of “open abdomen” according to M. Bjork (2016).

RESULTS: A total of 169 patients were treated. At the first stage of treatment, 63 (37%) operations of preventive enterocutaneus fistulaformation were done. On other indications, 60 more operations were done. During treatment, fistulas closed in 19 (11%) patients, and 20 (12%) patients died, 8 of them from the progression of cancer. In addition, 5 (3%) patients did not undergo reconstructive surgery due to the patients’ refusal of further surgical treatment. At the second stage, 125 patients were operated on. Fistulas were eliminated simultaneously in 112 (90%) patients, the other 13 (10%) required another planned staged surgical treatment. The incidence of severe postoperative complications (Clavien-Dindo grade III–V) was 23% (29), and the overall mortality was 15% (25).

CONCLUSION: Treatment of patients with enteroatmospheric fistulas should be carried out by an experienced multidisciplinary team in compliance with current standards and approaches.

BACKGROUND: In the population of patients with chronic kidney disease, higher levels of microbial-derived uremic toxins, regardless of the presence of traditional risk factors, predict an increased risk of adverse outcomes due to various cardiovascular complications. Meanwhile, the mechanisms of this association remain largely unexplored.

AIM: To study associations between concentrations of microbial-derived uremic toxins indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide and vascular remodeling in patients receiving hemodialysis treatment.

METHODS: This study included 80 hemodialysis patients and 80 individuals with normal kidney function. The groups were comparable by gender, age, body mass index and smoking intake status. The presence and severity of vascular remodeling were assessed using cardio-ankle vascular index, carotid intima-media thickness, abdominal aortic calcification scores and brachial artery endothelium-dependent vasodilation (flow-mediated dilation). The concentrations of indoxyl sulfate and p-cresyl sulfate in blood serum were determined by ELISA. The serum levels of trimethylamine-N-oxide were assessed by liquid chromatography/mass spectrometry.

RESULTS: Compared with healthy controls, dialysis patients showed significantly higher cardio-ankle vascular index (9.5 ± 1.5 vs. 7.8 ± 1.2, p < 0.001) and carotid intima-media thickness (1.04 ± 0.2 vs. 0.95 ± 0.15 mm, p = 0.001), as well as lower flow-mediated dilation (3.9 ± 1.2 vs. 7.5 ± 0.8%, p < 0.001). The median abdominal aortic calcification in this group was 4.5 (0–9.0). In the multivariate regression analysis adjusted for other dependent factors, indoxyl sulfate was found to be an independent determinant of cardio-ankle vascular index (β = 0.266; p = 0.002) and carotid intima-media thickness (β = 0.372; p = 0.001). Similarly, p-cresyl sulfate was a predictor of cardio-ankle vascular index (β = 0.143; p = 0.048) and abdominal aortic calcification (β = 0.21; p = 0.032), while trimethylamine-N-oxide was independently associated with cardio-ankle vascular index (β = 0.223; p = 0.004), carotid intima-media thickness (β = 0.208; p = 0.024) and flow-mediated dilation (β = −0.262; p = 0.004).

CONCLUSION: The relationship between an increased serum microbial-derived uremic toxins and surrogate markers of cardiovascular diseases (cardio-ankle vascular index, carotid intima-media thickness, abdominal aortic calcification and flow-mediated dilation) found in this study may indicate a significant role of indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide in vascular remodeling in individuals receiving hemodialysis treatment.

Melanoma is a highly malignant tumor with a tendency to early and aggressive metastasis. Melanoma metastases in the gallbladder are found in 20% of patients with melanoma according to autopsy data, however, intravital detection of metastases is a rare case in clinical practice, which is associated with the asymptomatic course of the disease in 85% of patients. The prognosis for detecting a secondary lesion of the gallbladder in melanoma is extremely unfavorable due to late diagnosis and the high probability of concomitant metastasis. The key to prolonging survival of these patients is early detection of metastases and initiation of immediate and radical treatment. The presented clinical observation demonstrates an example of identifying metastasis of skin melanoma to the gallbladder after a two-year remission of the disease. As in most cases, the course of the disease was asymptomatic, and the reason for planned surgical treatment was the formation of the gallbladder, presumably a polyp or a conglomerate of stones, which were identified by computed tomography. Metastasis of skin melanoma to the gallbladder was confirmed by pathohistological examination of the surgical material. In patients with a history of melanoma, a thorough examination of the hepatobiliary tract should be carried out using the most informative diagnostic techniques for the timely detection of metastatic foci.

Hyperuricemia is a condition characterized by an increase of serum uric acid level above 360 µmol/L. It is known that high serum uric acid levels are not only the condition for the etiopathogenesis of gout but also an important risk factor for the development and progression of cardiovascular diseases, kidney and liver pathologies, type 2 diabetes, and others. This makes hyperuricemia a relevant issue in general therapeutic practice. Despite extensive evidence on the negative role of hyperuricemia in many internal organ diseases, the management strategy for patients with asymptomatic hyperuricemia in real clinical practice remains a subject of debate.

This resolution represents an interdisciplinary consensus of experts from Commonwealth of Independent States, based on current evidence-based medicine data and proprietary registries. The proposed algorithm emphasizes the importance of a personalized approach to the treatment of hyperuricemia, taking into account the severity of comorbid conditions and the level of cardiovascular risk. Step-by-step recommendations are provided for general practitioners, family doctors, and a wide range of specialists in both non-pharmacological and pharmacological urate-lowering therapy. These guidelines aim to improve the quality of medical care for patients at high risk of socially significant diseases occurring together with asymptomatic hyperuricemia.