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Research and Practical Medicine Journal

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Vol 6, No 3 (2019)
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https://doi.org/10.17709/2409-2231-2019-6-3

Original Articles. Оncology

10-19 1044
Abstract

Aim. To identify the association of NFKB1, HIF1, VEGFA, VEGFB, BAX, BCL2 gene expression in prostate adenocarcinoma cells with biochemical recurrence of localized prostate cancer.

Patients and methods. Three groups of patients were formed in the study – the main one, the comparison group and the control group. In patients with prostate cancer (PC) in the main group (n = 56) with biochemical recurrence (BR) for two years after radical surgery, as well as in 60 patients without BR (experimental group) by real-time PCR in prostate cancer tissue the expression of genes NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2 was determined. The control group consisted of 55 patients in whom, when performing diagnostic punctures for benign prostate tumors, biopsy specimens were taken in healthy tissues. The age of patients in the three groups ranged from 57 to 74 years (median 63 years). When quantifying expression of genes NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2, the difference in the values of reaction threshold cycles (Ct) fixed for the studied and reference genes was determined. The relative level (Expr) was the ratio of Ct medians for each gene in two compared groups of the studied three ones: in the main group to the indicator in the control group, in the experimental group to the indicator in the control group, and also between the main group and the experimental group.

Results. A comparative analysis of gene expression in prostate cancer tissue in the main group compared with the experimental group showed a statistically significant increase (p < 0,05) in the relative index for the HIF1 gene (2,7 times), the VEGFA gene (2,4 times ) and the NFKB1 gene (2 times). Consequently, in patients with localized early recurrence prostate cancer, initially in the prostate tissue, a higher level of expression of the NFKB1, HIF1 and VEGFA genes was established. In the experimental group relative to the control group, the expression of the proapoptic gene BAX was 1,6 times higher (p < 0,05), and for the antiapoptic gene BCL2 no changes were detected (p = 0,09). Thus, in patients with localized prostate cancer in the absence of BR, after radical prostatectomy, an initial increase in the expression of the BAX gene promoted the activation of apoptosis. In patients with localized prostate cancer, subsequent biochemical recurrence initially in the tissue of prostate adenocarcinoma inhibition of apoptosis due to increased expression of the BCL2 gene was observed.

Conclusion. Enhancement of NFKB1, VEGFA, HIF1 and BCL2 gene expression in prostate tissue is associated with the development of BR in patients with localized prostate cancer.

20-28 857
Abstract

Aim. Study of VEGF-A and TGF-β growth factors in tumor tissue bioptates in patients with squamous cell carcinoma of the tongue and floor of the oral cavity depending on the effectiveness of polychemotherapy targeted therapy with cetuximab.

Patients and methods. The study included 30 patients with squamous cell carcinoma of the tongue and mouth floor mucosa (T3-4N0-1M0). All patients received 2 cycles of therapy: cisplatin 100 mg/m2 , intravenously, day 1, 5-fluorouracil 1000 mg/m2 /day, intravenously, 96-hour continuous infusion in combination with targeted therapy (cetuximab 400 mg/ m2 on day 1 in a loading dose, then 250 mg/m2 on days 8 and 15). Patients were divided into two subgroups: target sensitivity of patients (partial regression and stabilization) n = 17 and target resistance (progression) n = 13. Levels of growth factors VEGF-A and TGF-β were determined in tumor tissue bioptates by ELISA using standard test systems (Bender Med System, Austria). Statistical processing of results was performed using the Statistica 6.0 program (Stat-Soft, 2001).

Results. Polychemotherapy with cetuximab in some patients (n = 13), antitumor therapy with cetuximab did not result in statistically significant changes in levels of VEGF-A, TGF-β and the VEGF-A/TGF-β ratio compared to the initial values. In other patients (n = 17), the studied markers in tumor tissue bioptates were statistically significantly different from the initial values: VEGF-A was decreased by 1.46 times, TGF-β by 2.96 times, while the VEGF-A/TGF-β ratio was twice elevated.

Conclusions. The results on levels of growth factors VEGF-A and TGF-β, as well as the VEGF-A/TGF-β ratio, are of a certain prognostic value and can be used as criteria for evaluating the efficacy of antitumor therapy in patients with squamous cell carcinoma of the tongue and mouth floor mucosa.

29-39 1270
Abstract

Aim. To assess the immediate and long-term results of treating patients with bilateral lung cancer (LC).

Patients and methods. Radically operated 5 patients with primary multiple synchronous LC (PMSLC) and 5 patients with primary multiple metachronous LC (PMMLC) were included in the study. Clinical and morphological data, results of instrumental studies, immediate and long-term treatment results were analyzed. Statistical analysis was performed using the Statistica6 software.

Results. Tumors corresponding to T1‑T2 prevailed in both groups. At the same time, both in the PMSLC and PMMLC group, only in one case both tumors corresponded to T1–2N0M0, in the others — one or both tumors were with metastases in lymph nodes of the root or mediastinum. In early postoperative period, the number of surgical complications was 10%, somatic — 20%. All complications were successfully treated conservatively. Postoperative mortality was not observed. In PMMLC and PMSLC cases, one-year relapse-free survival (RFS) was 100% and 80%; two-year — 80% and 60%; three-year — 60% and 60%; four-year — 60% and 20%, respectively. The five-year RFS in patients with PMMPC was 40%. One patient with PMSLC was alive without relapse of disease for 4.5 years. Accordingly, one-year overall survival (OS) was 100% and 100%; two-year — 80% and 80%; three-year — 80% and 60%; four-year — 80% and 40%. Five- and six-year OS in patients with PMMLC were 60% and 20%, respectively.

Conclusion. The absence of postoperative mortality and low number of postoperative complications indicate the safety of bilateral operations in patients with bilateral LC. Low rates of patients’ 5‑year survival are connected with problems of primary diagnostics and low efficiency of existing algorithms of regular medical checkup of patients with this pathology. To improve long-term results of LC treatment, it is necessary to more actively introduce the modern programs of dynamic observation and complex examination of patients, undergone surgery for LC, using the annual chest CT and fibrobronchoscopy.

Original Articles. Radiodiagnosis, Radiotherapy

40-50 1054
Abstract

Purpose of the study. A comprehensive quantification of ectopic fat depots using modern methods of radiation diagnosis in patients with ischemic heart disease.

Patients and methods. The study included 76 patients with a verified diagnosis of ischemic heart disease (IHD). The control group consisted of 32 people without clinical manifestations of IHD. All patients to assess the area and volume of visceral adipose tissue, as well as measuring the volume of paraaortic adipose tissue at the level of the abdominal aorta were performed multispiral computed tomography (MSCT) at the level of L3–L5 vertebrae. In order to visualize and morphometry pericoronary and paraaortic adipose tissue at the level of the thoracic aorta, patients in both groups were performed MSCT angiography of the coronary arteries with ECG synchronization. To visualize the epicardial fat depot with an assessment of the thickness of the adipose tissue layer, magnetic resonance imaging (MRI) of the heart was performed.

Results. During the comparative analysis, significantly higher values of quantitative indicators of the main ectopic fat depots were noted in patients with coronary artery disease. Estimation of the prevalence of obesity according to BMI data in the compared groups showed no significant differences. Considering the standard values of the area and volume of visceral adipose tissue, the prevalence of obesity was significantly higher in the group of patients with IHD. Conducted correlation analysis showed the relationship of quantitative indicators of ectopic visceral, para-aortic and epicardial fat depots. Moreover, in the group of patients with IHD, stronger correlations were found between the fat depots of different localization (r = 0,71, p = 0,013 in group with IHD and r = 0,59, p = 0,039 in group without IND).

Conclusion. Modern tomographic methods allow for a comprehensive quantification of ectopic fat depots. Significantly higher morphometry indices of the studied fat depots in patients with coronary artery disease demonstrate the need to develop a unified diagnostic algorithm for reliable stratification of cardiometabolic risk.

Review

51-64 1434
Abstract

Pancreatic cancer (PC) is a lethal malignant tumor characterized by a rapid progression, invasiveness and resistance to radiochemotherapy. The development of biomarkers for the early diagnosis of the disease is relevant. Angiogenesis has been identified as a key factor in a number of pathological conditions, including cancer. The proangiogenic signaling molecule – vascular endothelial growth factor (VEGF) and its receptors play a central role in tumor angiogenesis. In this review, we also highlight the dual role of growth factor-β (TGF-β) and touch upon the prospects for therapeutic effects on targets associated with TGF-β signaling in pancreatic cancer. A growing interest is attracted to the role of insulin-like growth factors IGF-I and IGF-II in cancer diseases. IGF-I and its receptor are highly expressed on the surface of pancreatic cancer cell lines that initiate the transduction of intracellular signals associated with the proliferation, invasion and expression of angiogenesis mediators. And so, the study of markers and growth factors may be a new, viable option for the diagnosis and treatment of pancreatic cancer.

65-73 1049
Abstract

Inguinal hernia is a common disease affecting about 5-10% of the population. About 370 000 inguinal hernia repair per year is registered in Russia. Surgeons have reduced recurrence of hernias to a minimum after the widespread introduction of non-tension hernia repair. However, today other complications of inguinal hernias have become prevalent: infection, pain and paresthesia in the scrotum, pathospermia. Opinion about the negative impact on spermatogenesis of both herniation and surgery for hernia is still controversial. This article provides an overview of modern foreign and Russian literature on the аssociation of different types of inguinal hernia repair with pathospermia.

74-86 1723
Abstract

Erectile dysfunction is no longer a psychosocial problem. Nowadays, it is a marker specific for the initial stages of cardiovascular diseases. Рlatelet-rich plasma (PRP) is a new and promising method, which totally deserves to be noted by specialists. To review currently existing pre-clinical and clinical studies concerning application of PRP in erectile dysfunction published in international sources such as PubMed, Cochrane Library, Clinicaltrials.gov. The current data of preclinical and clinical studies determine the absence of PRP side effects and the effectiveness for ED treatment. PRP-therapy is a pathogenetically substantiated method of treating erectile dysfunction. The therapy is designed for repair and regeneration of endothelium, smooth muscle cells, and connective tissue. However, large, placebo-controlled, multicenter studies are needed to creation a systematic review and meta-analysis.

87-97 4718
Abstract

The article discusses the effectiveness of herbal medicine in inflammatory diseases of the prostate. This literature review presents clinical studies of the successful use of herbal ingredients in the treatment of chronic prostatitis and relief of lower urinary tract symptoms (LUTS). Biological active substances of Urtica dioica, Cucurbita moschata, Saw palmetto (Serenoa repens), and zinc are effective in the treatment of chronic prostatitis due to anti-inflammatory, antiproliferative, antiandrogenic and antioxidant action. Phytopreparations containing these substances can be recommended as the first line of correction of LUTS in chronic forgive categories III and IV; as a general tonic for men leading a sedentary lifestyle over the age of 35 years.

Clinical and Laboratory Observations

98-107 1320
Abstract

There are various methods of restoring the integrity of the pelvic ring, after surgery in patients with tumor lesions of the pelvic bones, allowing to keep the limb with good oncological and functional results. A new stage in the development of organ conservation treatment in this group of patients is the use of modular endoprostheses based on the conical leg. The development of postoperative complications leads to an unsatisfactory result of treatment, despite the radical surgery and technically correct endoprosthesis. This, in turn, leads to repeated surgical interventions, namely to remove metal structures, or to perform a crippling operation.

Purpose. To analyze postoperative complications and methods of their treatment in patients after modular endoprosthesis replacement of the acetabulum.

Patients and methods. From 2011 to 2018, surgical treatment of endoprosthesis using modular metal structures based on a conical leg was performed in 30 patients. There were 13 men (43%) and 17 women (57%). The median age was 45 years (23–63 years). Primary malignant tumors of pelvic bones were in 19 (63%) patients, 5 (17%) had a giant cell tumor. Two (7%) patients had solitary metastases of kidney cancer and one (3%) with synovial sarcoma, and 3 (7%) had relapses after previous surgical treatment.

Results. The average follow-up period was 36 months. Progression of the disease in terms of 6 to 40 months was revealed in 10 patients (33%), 8 (27%) of which died, the remaining 22 (67%) are alive with no signs of progression. In the postoperative period, 11 (37%) patients developed complications with predominance (up to 30%) of infectious. The average functional result on the MSTS scale was 59%.

Conclusion. The use of modular prostheses on the basis of a conical leg in patients with tumors of the pelvic bones allow to perform safe operations with a satisfactory functional and oncological result. The result obtained in our study is comparable with the data of world literature.

108-114 907
Abstract

Purpose of the study. To determine the effect of nutritional deficiency and nutritional therapy on the quality of life of patients with gastric cancer at the stage of surgical treatment.

Patients and methods. In Thoracoabdominal Department of P. Herzen Moscow Oncology Research Institute within 2017– 2019 the quality of life at the stage of surgical treatment of gastric malignant neoplasms was evaluated in 62 patients (36 men and 26 women) aged 34 to 79 years (mean age 61.9 ± 9.55). At the outpatient stage, patients were divided into 2 groups: in the 1st (main) group, patients received nutritive support with specialized mixtures for 10 days before hospitalization, in the 2nd (control) group, patients were asked to follow a high-protein diet without adding specialized mixtures. The quality of life assessment was carried out on the basis of the EORTC-QLQ-C30 Questionnaire, which patients received on the day of hospitalization. Patients repeatedly filled in EORTC-QLQ-C30 Questionnaire before discharge from the hospital, which allowed to assess the dynamics of the quality of life indicators of the studied patients. The study groups were comparable in social and medical indicators.

Results. The analysis of the survey results showed that the “general state of health” in the studied groups at the stage of hospitalization is estimated above average. Also, in both groups there is a positive dynamics in the values of the above indicator before discharge. Patients of the 1st group who received specialized nutritional mixtures, developed the statistical significance of the differences in the assessment of the quality of life upon admission and before discharge. Thus, it can be argued that nutritional therapy had a significant positive impact on the quality of life in terms of “general health”, in contrast to the control group of patients who did not receive specialized nutritional therapy. There was a general tendency toward an increase in the quality of life indicators at admission and before discharge on all scores of the questionnaire in groups. This is a positive assessment by patients of their condition after providing them with medical services. In this case, the discomfort from the symptoms accompanying the disease is reduced, which is confirmed by the scoring results. Statistically significant differences in the assessment of symptoms occur in the study group. Patients having received nutritional therapy noted a decrease in pain, an improvement in the processes of assimilation of food, as well as an improvement in well-being, physical condition, an increase in general tone and energy, a surge of strength and a sense of vitality. In “decreased appetite”score the indices of patients in the main group decreased by more than 3 times, i. e. their appetite improved significantly under treatment. Improving appetite in patients of the main group led to an improvement in the functioning of the gastrointestinal tract as a whole. Patients in this group noted an improvement in digestion and bowel movements.

Conclusion The study showed that the quality of life of patients with gastric cancer largely depends on their nutritional deficiency, and nutritional therapy at the stages of surgical treatment, in turn, can significantly improve its results, including in the aspect of their perception by patients. Using the general EORTC QLQ-C30 questionnaire is one of the available methods for assessing the quality of life in patients with gastric cancer.

Clinical Case Reports

115-128 793
Abstract

The treatment of common forms of squamous cell carcinoma of the organs located on the head and neck that are not subject to surgical treatment is limited to the use of chemoradiotherapy with platinum derivatives or drug therapy with platinum-containing regimens. With the progression of the disease, ineffective 2‑line cytostatics were prescribed that did not fundamentally change the course of the tumor process. The introduction into clinical practice of drugs of the original mechanism of action has significantly increased the effectiveness of drug therapy during progression after platinum-containing chemotherapy. The article presents two clinical observations that demonstrate the relevance of the strategy of using inhibitors of immune response control points after platinum preparations.

129-137 1203
Abstract

Testicular cancer is a rare malignant tumor. In the structure of general cancer incidence, this nosology accounts for about 1–1.5% of cases. Among this pathology, about 90–95% is due to testicular germ cell tumors. Currently, testicular cancer is a potentially treatable solid tumor with a 10-year survival rate of more than 95% upon timely diagnosis and proper treatment. In this regard, early diagnosis and treatment of this pathology is an urgent task today. The article presents a clinical observation of the treatment of a patient with a testicular germ cell tumor. The presented clinical case demonstrates the successful conduct of neoadjuvant chemotherapy and further orchifuniculectomy in the presence of distant metastases namely in case of a non-seminomic form of a testicular germ cell tumor. The approach to treating patients with testicular tumors must be individualized and take into account both the potential gain and the potential risks of the treatment being performed.

Health Organization

138-145 1117
Abstract

The new economic policy of Russia is based on innovation and investment. Before choosing innovative changes, it is mandatory to assess the innovative potential of the organization. can distinguish Three main components can be distinguished in the innovative potential of a medical institution: innovative potential of medical personnel, innovation of facilities and resources, technology innovation (medico-institutional, therapeutic and diagnostic technologies). An audit of the innovative potential of a medical organization is a prerequisite for the formation of a competent economic policy, i. e. business strategies, priority investments. However, studies on a comprehensive assessment of the state of innovative potential of oncological medical organizations have not been conducted yet.

Objective. To study the state of innovative potential of a medical organization, as part of its economic policy, using the example of cancer care.

Materials and methods. The base of the research is the Higher Educational Institution “Ivanovo Regional Oncology Dispensary”, Department of Health, Ivanovo Region. The research program provided for the use of sociological, expert, mathematical-statistical and analytical methods. Units of observation: medical worker (doctor, paramedical worker) and material and technical resources of “Ivanovo Regional Oncology Dispensary”, The study was conducted in 2018. The integral estimation methodology of a medical organization’s innovation potential includes a quantitative assessment of each component of the potential according to the appropriate methodology.

Results. Decline of the innovative capacity medical organization oncological profile on all of its components including: a personnel component at 9,0%, logistical component to 11,0%, technological component at 6,8%. Reduced innovative capacity of health workers is associated with low estimation of its parameters such as: the use of information sources for self-development, the ability to adapt to innovation and research activity. A decrease in the innovative potential of an oncological medical organization was noted in all its components, including: the personnel component by 9.0%, the material and technical component by 11.0%, the technological component by 6.8%. The decline in the innovative potential of health workers is associated with a low assessment of its parameters such as the use of information sources for self-development, the ability to adapt to innovation and research activities. The decrease in the innovation of the organization’s facilities and resources is associated with such indicators as: the scientific and technical level of equipment, the coefficient of accumulation of fixed assets, the coefficient of depreciation of equipment, the coefficient of inclusion of equipment in the standard of assistance. The decrease in innovation in the technological component is associated with the incomplete implementation of such quality attributes of medical services as: efficiency, adequacy, interpersonal interaction, uniqueness, convenience.

Conclusion. The results of the study showed that a change in the innovative policy of medical organizations is required, its transfer from an extensive to an intensive strategic vector of development, the use of free financial resources for the purchase of new generation equipment, and the training of medical personnel in modern work technologies.



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