Sechenov Medical Journal

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Vol 10, No 3 (2019)
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4-12 503
We hypothesize that the anti - apoptotic response in mesenchymal stem cells (MSC) under low doses of radiation may develop through the participation of an extracellular mediator of signal transmission between cells - fragments of oxidized cell - free DNA (cfDNA).Aim. To investigate the effect of radiation in low doses (10 sGy) and oxidized fragments of cfDNA on the activation of genes in MSCs signalling cascades that regulate the cellular response to DNA damage. Materials and methods. We investigated the effect of radiation in low doses (10 cGy) and fragments of oxidized cfDNA (concentration 50 ng/ml) on the activation of signalling gene cascades in MSC that regulate the cellular response to DNA damage.Results. We have shown, that in MSC under small doses of radiation for 15-40 minutes the transcriptional activity of pro - apoptotic genes is activated, the level of apoptosis increases and due to the death of part of the cells in the culture of MSC, fragments of oxidized cfDNA are formed. 3-72 hours later the expression of genes ING2, HUWE1, TP53, BBC3, NOXA, P53AIP1, BAX, BAK1, MMP7, ENDOG decreases 1.5-3 times ( p <0.01), which is accompanied by an increase of the antiapoptotic genes expression: BCL2, BCL2A1 (Bfl-1/A1), BCL2L1 (BCL-X), BIRC2 (c-IAP1) by 2-4 times ( p <0.001), and, as a result, a decrease in the level of apoptosis. Since the regulation of gene expression in MSC in response to radiation and to the action of the oxidized cfDNA fragments is the same, we can assume that one of the factors of stress signalling in the action of radiation in low doses can be cfDNA fragments of dead cells.Conclusion. Small doses of radiation and oxidized cfDNA may activate a signalling pathway in MSC, that regulates the response to DNA damage, leading to an antiapoptotic response.
13-21 337
Aim. To evaluate the effectiveness of the combined effects of biological feedback (BFB therapy) and electroimpulse stimulation (EIS) in rehabilitation of patients with pelvic floor dysfunctions. Materials and methods. A comparative prospective study included 235 women with clinical and ultrasound signs of genital prolapse stages I-IV according to POP-Q. The observation program was completed by 209 patients who were divided into group 1 with stage I-II prolapse and group 2 with stage III-IV prolapse. Vaginal extraperitoneal vaginopexy with installation of mesh implant was performed in group 2 patients before inclusion in the study. Lifestyle modification was recommended for all patients. In each group, patients were divided into subgroups of control and treatment (BOS-therapy and EIS). Group 1: subgroup A - control (n=47), subgroup B - treatment (n=56); group 2: subgroup C - control (n=49), subgroup D - treatment (n=57). Index of influence on the quality of life (IQOLI) and parameters of ultrasound were evaluated.Results. After a year of observation, in subgroup A, the IQOLI decreased by 5%, in subgroup B by 64% ( p< 0.05); in subgroup C, IQOLI decreased by 32%, in subgroup D - by 63% of the initial value ( p <0.05). In subgroup B, there was a statistically significant decrease in the size of the anterior urethro - vesical angle during the Valsalva test and in rotation of the alpha angle under load, leveling or reducing signs of genital prolapse in all patients. In subgroup A, the ultrasound parameters did not change, the dynamics of the prolapse stages were not noted. After a year of the program, the size of the anterior urethro - vesical angle at rest statistically significantly decreased in subgroups C and D. In subgroup D, the rotation of the alpha angle during loading, the size of the anterior urethro - vesical angle during the Valsalva test, and the smoothness of the beta angle at rest also decreased. In subgroup C, 4 (8%) cases of recurrence of genital prolapse were recorded; in subgroup D, no relapses were observed ( p =0.023).Conclusion. In patients with genital prolapse, both I-II stages and III-IV stages after surgical treatment, the use of biofe - edback therapy and EIS are more effective than the standard recommendations for lifestyle modification with regard to reducing IQOLI and changing ultrasound parameters. Adherence to rehabilitation program was 89%.
22-29 389
Because of the high incidence of breast cancer in the population, breast reconstruction remains actual after complex cancer treatment.Aim. To characterise revascularization methods based on deep inferior epigastric perforator flaps (DIEP flap), test the frequency and risk factors for perfusion related complications. Materials and methods. The study included 157 patients, with 190 reconstructions performed. The tactics of choosing donor and recipient vessels were determined using an intraoperative assessment of the dominant blood supply system: sample with blood flow stop.Results. In most reconstructions, the deep inferior epigastric arteries were the main source of blood supply to the flap. Non - standard revascularization was required in 14% of cases and was associated with prior interventions on the anterior abdominal wall or individual characteristics of its blood supply. Venous super - drainage was performed in 30% of cases. Most often, the perforating veins of the anterior chest and the retrograde pedicle of the internal chest vein were used as recipient vessels. Complete flap loss occurred in 2% of cases. We observed perfusion complications in 17% of cases, statistically significantly more often in smokers ( p <0.001). A history of radiation therapy as an independent risk factor was not associated with an increase in the frequency of complications. The combination of risk factors “smoking + radiation therapy” was observed more often in patients with perfusion complications ( p =0.042). Imposing additional venous drainage was associated with a statistically significant decrease in the frequency of perfusion disorders: 2% among all flaps with venous super - drainage and 23% without drainage ( p <0.001).Conclusion. Intraoperative assessment of the dominant blood supply system using a sample with blood flow stop allows you to determine the nature of the dominant systems of arterial inflow and venous outflow in the DIEP flap accurately. Risk factors for the development of perfusion complications are smoking and previous radiation therapy in combination with smoking.
30-36 313
Aim. To experimentally test a new method for plastic surgery of a critical defect in the tracheal wall using a cell engineering construction and a stent. Materials and methods. The object of the experiment was 13 Oryctolagus Chinchilla rabbits. To determine the critical size of the tracheal defect, a “Defects Group” (n=11) was created, divided into two subgroups depending on the width of the mucous and submucosal defect, the length of the defect was standard - 15 mm. Subgroup 1 included animals with a defect width of <50% of the tracheal circumference (n=5), subgroup 2 - animals with a defect width of ≥50% of the tracheal circumference (n=6). After critical tracheal defects were created, two more rabbits underwent plastic surgery using a cell - engineering construct fixed in the trachea's lumen using a vascular stent. (“Reconstruction Group”). After removing animals from the experiment, we performed a macro and microscopic examination. Results. In subgroup 1, postoperative mortality was not registered, animals were withdrawn from the experiment on the 14th day. Macroscopically: a slight but noticeable tracheal narrowing, microscopically: a thin, weak submucosal layer and an epithelial film without purulent inflammation. In subgroup 2, postoperative mortality was 100% on the 4th day. Macroscopically: a hematoma at the site of defect, the mucous membrane is swollen, the lumen of the trachea and large bronchi is obstructed by mucus, microscopically: massive detritus. We recognise the defect in subgroup 2 as critical. In the “Reconstruction Group” postoperative mortality was not registered. Animals were withdrawn from the experiment on the 14th and 20th days. The trachea is separated from the stent, the lumen is not narrowed, and the matrix is partially fragmented. Macroscopically: absence of severe hematoma and oedema, microscopically: multiple zones with the regeneration of the submucosal layer and mucosa. Conclusions. A critical tracheal defect in rabbits is an epithelial and submucosal defect with a length of 15 mm and a width of ≥50% of the circumference of the trachea. The plasticity of a critical defect with the help of a cell engineering design and a stent showed its viability in the experiment.
37-44 410
Prostate cancer (PCa) is the most common oncological disease among men. It is important to note that over 50% of the first identified primary malignant neoplasms of prostate are low - risk PCa. Recently, radical prostatectomy and external beam radiation therapy have been the standard treatment options for PCa. According to recent data, patients with low - risk PCa have a favourable prognosis because of the slow progression of the disease. Some studies show no links between 10-year cancer - specific survival and treatment modalities and no progression even in the absence of therapy. Active surveillance (AS) allows avoiding unnecessary treatment in men who do not require immediate intervention but achieves the correct timing for curative treatment in those who eventually need it. According to the guidelines of the European Association of Urology, AS is one of the standard treatment options for low - risk PCa and should be consideredfor all patients in this category. The advantage of AS is to improve the quality of life in men with low - risk PCa and to delay surgical interventions as much as possible. However, despite widespread AS worldwide, there are only a few centres, which use it routinely in Russia. In this review, we would like to shed some light on the most important questions of AS strategy: what criteria should we use for selection of patients for AS strategy? How often should patient visit the urologist, control PSA level, and undergo prostate biopsy? When should a doctor change strategy and turn to active treatment? In this article, we considered indications for AS in men with PCa and showed the most recent data on the efficacy and relevance of this modality.
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Perceptions of hepatitis E have transformed over the past decade. This infection was common only in some developing countries. It is known now that hepatitis E occurs in most high - income countries and is largely a zoonotic infection. The review analyzes the relevant key publications and recommendations on the diagnosis and treatment of hepatitis E. Theproblems of diagnosis, treatment and prevention of hepatitis E caused by genotypes 3 and 4 are highlighted. It is shown that with symptoms of acute hepatitis for hepatitis E virus infection (HEV) it is advisable to test not only travelers returning from areas endemic for 1 or 2 genotypes (Asia, Africa, Mexico) and pregnant women, but also all patients, after excluding other reasons for changing liver tests. Testing for HEV is also recommended for patients with chronic liver disease with unexplained deterioration, for patients with immunosuppression and changes of liver tests, for patients with systemic manifestations of diseases of the nervous system. A combination of serological testing and nucleic acid amplification methods are recommended for the diagnosis of HEV infection. Treatment of HEV infection includes the use of antiviral therapy in severe cases; if possible, for patients who underwent transplantation of solid organs - a reduction in doses of immunosuppressive drugs for pregnant women - intensive therapy. Prevention of HEV infection is aimed at people with chronic liver diseases and receiving immunosuppressive therapy who should be excluded from the use of mollusks and poorly fried pig, boar and deer meat.
54-60 441
Introduction. Craniopharyngioma (CF) is the most common non - glial benign intracerebral tumor among children, which can be removed by both microsurgical and endoscopic methods. Case report. A 16-year - old patient was hospitalized with complaints of decreased visual acuity and a bursting headache. Based on neuroimaging data, CF of size up to 33.5×21×23 mm was detected that compressed chiasm, a suprasellar cistern and the bottom of the third ventricle. Surgery was performed to remove the tumor using transnasal endoscopic approach. Wide dissection of the tumor and bimanual endoscopic preparation made it possible to preserve the hypothalamus and the pituitary stalk. Histological examination of the removed tumor revealed an adamantine - like CF of the first degree of malignancy according to the WHO classification. The early postoperative period was uneventful, according to neuroimaging: the tumor bed was filled with content of fat density. A follow - up examination taken a year later did not reveal continued growth. Neurological improvement in the absence of a headache was confirmed, along with an improvement in visual acuity in the right eye, no hormonal disorders were found. Discussion. The transnasal endoscopic method for the removal of volumetric formations of the parasellar region in children is rarely used in practice due to the anatomical features. Our experience has shown good postoperative results of this technique in the treatment of CF in children, and we believe that this is a promising method of treatment for this pathology. But at the same time, we cannot argue that the method is suitable in all cases of parasellar tumour, so if the tumor size is more than 35 mm, we resort to the microsurgical technique, because in this case the transnasal approach does not provide total tumor removal.

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