Relapse-free Period Research Articles

Navigating Complexity in Pediatric NMOSD: Unusual Symptoms and Adverse Reactions: A Case Report

Background and Clinical Significance: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune demyelinating disorder of the central nervous system, characterized by the presence of aquaporin-4 (AQP4) antibodies and a high relapse rate. We provide information about the diagnosis, unusual symptoms, and treatment of a paediatric patient with NMOSD. Case Presentation: A 14-year-old girl was hospitalized for weakness and paraesthesia of the lower limbs (LL). The patient underwent detailed investigations and was diagnosed with NMOSD and cryptogenic organizing pneumonia. Initial treatment with methylprednisolone and prednisone yielded a favourable response. Therapy with mycophenolate was initiated. However, the patient experienced two more relapses, prompting the use of rituximab therapy with a favourable outcome and a two-year relapse-free follow-up period. Conclusions: Patients with NMOSD may have multisystemic inflammation, including organs outside the central nervous system. Our case report highlights a case of NMOSD, pulmonary involvement, and unusual adverse reactions to rituximab.

Blood laboratory parameters can predict relapse-free survival of patients with advanced squamous cell lung cancer and adenocarcinoma

The aim of the work was to study the relationship between the concentration of cells and proteins in the blood of patients with Stage III squamous cell lung cancer (SCLC) and adenocarcinoma (AC) before surgical treatment and the duration of the relapse-free period after tumor resection to develop prognostic models for relapse-free survival in these diseases. Using logistic regression equations, the models incorporated variables included cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) concentration, the proportion of lymphocytes expressing the C-X-C motif chemokine receptor 1 (CXCR1), and monocytes expressing the C-X-C motif chemokine receptor 2 for SCLC. For AC, the models included the CYFRA 21-1 concentration, lymphocytes expressing the CXCR1 receptor, and the eosinophil-to-monocyte ratio. These models can predict the probability of tumor recurrence based on measurements of blood parameters in the pre-operative period, with a prediction efficiency of 87.7% for SCLC and 89.0% for AC.

Clinical prognostic factors in patients with diffuse gliomas of the brain

BACKGROUND: Diffuse gliomas of the brain represent a heterogeneous group, which differs in age of the disease onset, histologic characteristics, tumor grade, molecular genetic markers and prognosis. AIM: of the present study is to identify the factors, which affect the duration of the relapse-free period and life expectancy in patients with diffuse brain gliomas, based on a comprehensive analysis of clinical syndromes and symptoms. MATERIALS AND METHODS: The study was carried out at the Departments of Neurosurgery and Nerve Diseases of the S.M. Kirov Military Medical Academy (Saint Petersburg, Russia). It included 390 in-patients with diffuse brain gliomas who underwent treatment over the periods of 2014–2022 and 2004–2006. Age at time of diagnosis was 45.26 ± 15.72 years old. The study included 218 (55.9%) male and 172 (44.1%) female patients. It was a single-centre prospective study. RESULTS: of the author’s research. Favourable demographic factors include the age range of 18–39 (relapse-free period duration p 0.01, life expectancy p 0.001) and female sex (relapse-free period p = 0.02, life expectancy p = 0.03). Prognostically favourable clinical manifestations include epileptic seizures before surgery (relapse-free period p 0.01, life expectancy p 0.02); unfavourable clinical manifestations are pyramidal syndrome (relapse-free period p 0.01, life expectancy p 0.001), sensitive disorders (relapse-free period p = 0.045–0.12, life expectancy p = 0.09–0.17), speech pathology (relapse-free period p 0.02, life expectancy p = 0.02–0.12) and cerebellar syndrome (relapse-free period p 0.02, life expectancy p 0.001). Clinical signs such as headache, nausea and vomiting, asthenia, diffuse neurological symptoms, craniocerebral nerve involvement and visual impairment do not affect (p 0.05) the outcomes of the patients with diffuse brain gliomas. CONCLUSION: Thus, favourable demographic prognostic factors include female sex and age range of 18–39, favourable clinical prognostic factors include epileptic seizures before surgery. Unfavourable clinical prognostic factors include presence of motor, sensory disorders, speech impairment and cerebellar syndrome.

Lymphocyte-monocyte index as a new marker for the prognosis of early recurrence of the disease in patients with glioblastoma

Every day, the number of scientific studies in the global medical community is growing, emphasizing the importance of the immune system in the prognosis and course of oncological diseases. The lymphocyte-monocyte index has already demonstrated its prognostic role in some forms of tumor disease. However, its significance in glioblastomas has not been fully determined.The aim of the study is to study the prognostic value of the lymphocyte-monocyte index for patients with glioblastoma.Material and methods. The study included 45 patients with primary supratentorial glioblastoma over the age of 18 who had reached the first relapse of the disease. In each case, the level of leukocytes, lymphocytes, monocytes and LMR (ratio of lymphocytes to monocytes) in peripheral blood before surgery was assessed, and symptomatic treatment with glucocorticosteroids was taken into account. The histological diagnosis was established in accordance with the WHO classification of Central nervous system tumors in 2021. All patients after the neurosurgical stage of treatment received standard antitumor treatment (radiation therapy, chemotherapy with temozolomide). The effect of LMR on the median of the first relapse-free period was studied.Results. A significant increase in the absolute number of monocytes was found in patients receiving dexamethasone therapy (p = 0.014). At the same time, the appointment of GCS did not affect the level of lymphocytes and LMR. The median of the first relapse-free period was statistically higher in patients with an LMR of more than 4 (p = 0.05; 47 vs 30.5 weeks).Conclusions. Low LMR is a marker of the prognosis of early recurrence of the disease for patients with glioblastomas. It is important to note that despite the fact that the level of monocytes was directly correlated with the appointment of glucocorticosteroids to patients, the LMR was not affected by the appointment of this group of drugs.

Obinutuzumab as a viable therapeutic strategy in rituximab-refractory childhood frequently relapsing, steroid-dependent nephrotic syndrome that relapsed during B-cell depletion.

A subgroup of children with frequently-relapsing, steroid-dependent nephrotic syndrome relapse during B-cell depletion after rituximab. A 15-year-old boy with focal segmental glomerulosclerosis became rituximab-refractory after 5 courses of treatments, with a relapse-free period shortened to 1month. Circulating total and memory B-cells were undetectable at the time of relapse. A single infusion of obinutuzumab sustained relapse-free remission up to the last follow-up at 18months. There was persistent hypogammaglobulinemia but no infection was observed. Obinutuzumab may be a viable option for attaining long-term remission with reasonable side effect profiles in patients who relapse during B-cell depletion after rituximab.

Efficacy of Doxorubicin in the Adjuvant Treatment of Canine Splenic Visceral Hemangiosarcoma

Introduction. Splenic hemangiosarcoma is a highly malignant neoplasm that affects geriatric patients. The incidence in dogs is 45–50% of all splenic tumours and about 2% of all oncological pathologies. The visceral form of splenic hemangiosarcoma is characterised by the most aggressive course of the disease and early metastasis to other organs. The average life expectancy of animals after splenectomy, according to various scientific data, is from 20 to 90 days. The article studies the efficacy of additional doxorubicin-based adjuvant chemotherapy to increase the life expectancy of dogs at different stages of the disease.Materials and Methods. To compare the life expectancy, the patients were divided into 4 groups receiving different treatments for splenic hemangiosarcoma. Examination of patients, visual diagnostics and pathomorphological diagnostics were used for making a diagnosis, determining the stage of the disease and prescribing treatment. Treatment efficacy was assessed based on the median relapse-free period, median life expectancy and survival rate of patients after 3, 6, and 12 month periods. Statistical analysis was performed using the Fisher's exact test.Results. The obtained data demonstrated a more favourable course of disease in dogs with the stage I tumour process. Splenectomy made it possible to increase the life expectancy of patients to 243 days with a 6–month survival rate in 62.5% of patients. Postoperative chemotherapy treatment combined with doxorubicin significantly improved the longterm prognosis and led to more than twofold increase in life expectancy of dogs (up to 475 days) with a one-year survival rate in 83.3% of patients. However, no substantial statistical significance was determined in the studied groups (p=0.7).Discussion and Conclusion. The results of the research have revealed the efficacy of adjuvant doxorubicin-based chemotherapy in dogs with the visceral forms of splenic hemangiosarcoma. In animals with early stages of the disease, a significant increase in life expectancy has been discovered. The development of hemagdomain and/or the presence of metastasis to abdominal organs indicate the unfavourable course of the disease and, as a consequence, early metastasis. Nevertheless, even at these stages, doxorubicin can increase the life expectancy of patients.

Плацебо-контролируемое клиническое исследование эффективности D-маннозы Суперкомплекс в профилактике рецидивов ИМП.

Introduction. In recent years, the use of D-mannose as an alternative to antimicrobial agents has been widely discussed in the literature due to the fact that when applied topically, it reduces the ability of E. coli to bind to the urothelium. The aim of this study was to evaluate the change in the number of relapses during the observation period in patients who used «D-Mannose Supercomplex» as a metaphylaxis of cystitis in comparison with the control group, which received a placebo instead of this product. Materials and methods. A multicenter, randomized, double-blind, placebo-controlled, prospective clinical study was conducted to evaluate the efficacy and safety of a dietary supplement containing 2000 mg of D-mannose, 100 mg of cranberry extract, 80 mg of bearberry extract (8 mg of arbutin), and 30 mg of magnesium. Results. In animal models, the use of D-mannose led to a significant decrease in the bacterial load. The use of «D-Mannose Supercomplex» prolongs the relapse-free period in patients with RUTI after the end of antibacterial therapy. The duration of the relapse-free period correlates with the duration of D-mannose intake, which is consistent with modern concepts of the mechanism of action of the drug. The drug is well tolerated by patients. The number of adverse events (AE) in the «D-Mannose Supercomplex» and placebo groups was comparable. AE and allergic reactions associated, according to the researchers, with the use of the study drug, were not registered during the administration of the drug. Conclusions. The presented study data indicate that complex drugs containing D-mannose, cranberry extract, bearberry and magnesium (for example, «D-Mannose Supercomplex») can be considered from the standpoint of evidence-based medicine as a promising means of complex etiopathogenetic therapy for prolonging the relapse-free period in patients with exacerbation of recurrent urinary tract infection (RUTI).

Possibilities of endoscopic adjuvant use of Mitomycin-S in the treatment of benign airway stenoses

Mitomycin-c is an effective and safe drug in the treatment of benign stenosis of the respiratory tract, to a greater extent increasing the duration of the relapse-free period, the interval between endoscopic manipulations. Due to the lack of clear ideas about the optimal method of administration of the drug, the timing, duration of the application / injection, it is necessary to continue further research.

Иммуномодуляторы в лечении женщин с хроническим рецидивирующим циститом.

Introduction. Chronic recurrent cystitis (CRC) is one of the most common urological diseases in women. Given the proven role of immune disorders in the development of chronic urinary tract infections (UTIs), insufficient effectiveness of antibacterial therapy, the risk of selection of resistant strains of microorganisms, the advisability of using immunomodulators is justified. The purpose of the study: to evaluate the effectiveness of the immunomodulatory drug Galavit® in the complex therapy of patients with CRC. Materials and methods. The study involved 68 women. The main group consisted of 36 patients who, in addition to antimicrobial therapy, were prescribed a course of Galavit® in the form of intramuscular injections for recurrent cystitis. The control group consisted of 32 patients who, in case of recurrent cystitis, received only standard therapy. The results were assessed 3 and 6 months after the start of therapy based on the clinical manifestations of the disease by filling in the questionnaires of acute cystitis symptoms (ACSS), visual analog scale (VAS) for pain and laboratory data (general urine analysis, urine culture data). Results. The inclusion of Galavit® in the complex therapy of CRC allows not only to quickly and effectively relieve the symptoms of exacerbation of the disease, but also to achieve a long and stable relapse-free period. Only 2 (5.5%) patients had a relapse of cystitis during 6 months of observation after complex therapy using Galavit®, while in the control group, clinical manifestations of relapse were registered in 13 (40.6%) patients. In addition, against the background of the use of Galavit®, the vast majority of women did not have clinically significant bacteriuria up to 6 months of observation (only 2 patients had asymptomatic bacteriuria after 6 months). Conclusion. The use of the immunomodulatory drug Galavit® can be effective not only for the purpose of increasing the effectiveness of the course of antimicrobial therapy during the period of exacerbation of CRC, but also for the prevention of relapses after clinical improvement has been achieved.

Nephronsparing surgery for retroperitoneal sarcomas

Objective: to clarify the indications for the use of nephron-sparing technologies in surgical treatment of patients with retroperitoneal sarcomas. Material and Methods. The study included 64 patients with primary retroperitoneal sarcomas with kidney and renal pedicle invasion, who underwent surgical treatment in the Thoracic-abdominal Department of the P.A. Herzen Moscow Oncology Research Institute from 2010 to 2021. Twenty-one patients underwent nephrectomies, and 43 patients underwent nephron-sparing surgery. The morphological profile of sarcomas, age and gender of the patients, feasibility of using nephron-sparing technologies, postoperative complications, and long-term outcomes in patients of both groups were analyzed. Results. Forty-three patients with primary retroperitoneal sarcomas with invasion of the renal parenchyma, ureter, and renal pedicle underwent nephron-sparing surgery (precision mobilization of the kidney, ureter and vascular structures of the kidney from tumor tissue, kidney resection, ureteral stenting, resection of the renal vein orifices, resection of the ureters, and kidney autotransplantation). Postoperative complications were observed in 19.0 % of nephrectomy group patients (4 pts: II, IIIB, IV and V types according to Clavien–Dindo) and in 30.2 % of nephron-sparing group patients (15 pts: types II – 8, IIIA – 1, IIIB – 3, IV – 1). No statistical differences in the relapse-free period and survival time between two groups were observed. The 1-, 3- and 5-year survival rates were 84.1 %, 65.9 %, and 51.4 %, respectively. Multifactorial analysis showed that mortality increased significantly in patients over 64 years of age and was associated with both disease recurrence and concomitant pathology (p=0.009). There was also a trend toward decreased survival in patients with leiomyosarcoma (p=0.066). Conclusion. In retroperitoneal sarcomas, tumor resection with preservation of organs and structures not directly invaded by the tumor is the optimal surgical strategy. Nephron-sparing technologies do not worsen both immediate and long-term treatment outcomes. For leiomyosarcoma, tumor resection with nephrectomy is the most suitable approach.

Comparative Study of the Effects of Docosahexaenoic Acid, Linoleic Acid, and Taxol in Decreasing the Expression of miR-10b, and miR-20a OncomiRs, and their Target Major Histocompatibility Complex Class I Chain-Related Proteins A (MICA) in Triple-Negative Metastatic Breast Cancer Cell Line

Background: Molecular signatures of the effects of widely used omega-3 and omega-6 fatty acids as dietary supplements and even in cancer therapy have been studied. Of them, microRNAs, have been shown to undergo altered expression after treatment with docosahexaenoic acid (DHA) and linoleic acid (LA) in different cancer types. In this study, the expression level of two well-known onco-microRNAs (miR), miR-10b and miR-20a, and also major histocompatibility complex class I chain-related protein A (MICA) as the target for these oncomiRs were investigated after treatment with DHA, LA, and common therapeutic agent Taxol. Methods: MDA-MB-231 cells were cultured in a complete RPMI 1640 medium and an MTT assay was performed to determine IC50 of DHA, LA, and Taxol. Cells were treated by DHA (100µM), LA (50µM), and Taxol (0.3µM) alone or in different combinations. After RNA extraction and cDNA synthesis, the expression levels of miR-10b, miR-20a, and MICA were determined by quantitative real-time PCR. U6 and β-Actin were used as endogenous controls, respectively. Results: Our findings showed that DHA, LA, and Taxol, and their combinations led to the significantly decreased expression of miR-10b and miR-20a (all P<0.0001). The expression level of miR-10b and miR-20a significantly decreased when treated with the LA+TAX combination. MICA as the target of miR-10b and miR-20a was also down-regulated significantly (P<0.0001) especially when treated with DHA+LA+TAX. Conclusion: Useful effects of DHA, LA, and their combination in breast cancer (BC) could be interpreted in part by decreasing the expression level of oncomiRs. In the case of MICA have had some contrary. High expression of MICA/B caused an approving outcome concerning the relapse-free period in early BC patients, however; some studies have shown that higher MICA expression was found as a sign of poor prognosis in BC. The decreased expression of MICA in the present study suggests the potential role of DHA and LA should be used in dietary supplements of BC patients.

Prognostic significance of hepatocyte growth factor in non-metastatic colorectal cancer

Hepatocyte growth factor (HGF), produced by mesenchymal cells, stimulates mitogenesis and angiogenesis in tumor cells. Tumor cells of some solid tumors do not secrete HGF. The aim of the study was to evaluate the prognostic significance of HGF expression in tumor tissue in colorectal cancer (CRC). The study included 50 patients with stage II-III colorectal cancer; they underwent radical surgical treatment, followed by adjuvant chemotherapy according to the FOLFOX/XELOX regimen. In primary tumor samples, quantitative PCR was used to assess the level of HGF expression. Statistical processing of the obtained data was carried out using STATISTICA 13.0, BioStat v.7.1., and Jamovi 1.6.8 software. The study aims to study a new marker. Comparison of characteristics in the case of non-normal distribution was carried out using the nonparametric Mann–Whitney U test. Cox and Kaplan–Meier linear regression tests were used to analyze progression-free survival. When discussing the results, we used our previously obtained data on the level of expression of TGF-β and CXCL8 in the tumor tissue. As a result of the studies, it was found that in 60% of tumor samples HGF was not expressed, but it was significantly higher than in the resection line samples. Analysis of relapse-free survival in patients with CRC according to the level of HGF expression (predicted level by proportional hazards assessment – 0.7) showed that the median survival in groups 1 (HGF expression more than 0.7) and 2 (HGF expression less than 0.7) was 23.3 and 62.9 months, respectively (long rank test p = 0.215). It was shown that the level of HGF mRNA in CRC tumors does not depend on age, stage of the disease, and sensitivity to FOLFOX/XELOX chemotherapy. The expression level is significantly reduced in tumors with a KRAS mutation and increased in those with a BRAF mutation, in poorly differentiated tumors. Using the level of HGF expression in the tumor tissue of patients with non-metastatic CRC before the start of chemotherapy to assess the prognosis of the relapse-free period is only possible in conjunction with the expression of TGF-β, CXCL8 in the tissue and the level of CEA in the blood of these patients.

Evaluation of the efficacy of Vesusten® in patients with overactive bladder and chronic recurrent cystitis

Introduction. Numerous studies have suggested that lower urinary tract infections may be involved in the development of overactive bladder (OAB) in patients who are resistant to standard treatment. In these cases, treatment targeting all stages of disease progression could be beneficial.Objective. To evaluate the efficacy of Vesusten® in management of OAB in women with chronic recurrent cystitis.Materials & methods. The study involved 40 patients diagnosed with OAB and chronic recurrent cystitis. All patients received Vesusten® as therapy for OAB. They received 5 mg of the medication intramuscularly three times per week for a total of 10 doses. The study included three stages: a screening period lasting up to 14 days; the stage for assessing the effectiveness of therapy (42 days from the start of therapy, including the therapy period + further follow-up after the end of therapy); follow-up period — 180 days + 14 days from completion of treatment.Results. It was revealed Vesusten® clinical effectiveness on the severity of OAB symptoms and the quality of life of patients. hree weeks after the end of treatment, there was a statistically significant decrease in the severity of OAB symptoms on the Patient Perception Index of Urgency and Symptoms (PPIUS) (2.2 ± 1.0 vs 0.95 ± 1.0 points) and TUFS (28.4 ± 11.6 vs 5. 1 ± 6.4 points), a decrease in the number of urinations during the day (11.5 ± 2.2 vs 8.8 ± 2.7 episodes) and at night (3.5 ± 1.8 vs 1.4 ± 1.5 episodes) time (p < 0.001). The nighttime urination frequency decreased by more than 2.5 times, while the proportion of patients who did not wake up at night for urination increased from 10 % to 35%. Evaluation of the Overactive Bladder Questionnaire (OAB-Q) after the completion of treatment compared with the initial data showed a statistically significant improvement in quality of life related to the severity of OAB symptoms (24.8 ± 7.5 vs 15.7 + 6.4 points; p < 0.001), and with general health status (74.0 ± 31.7 vs 57.6 ± 22.1 points; p = 0.0087). The average duration of the relapse-free period, including the course of Vesusten® treatment and the follow-up period, significantly increased to 42.90 ± 9.64 weeks in comparison with the duration of the relapse-free period before patients’ inclusion in the study — 17.96 ± 7.75 weeks (p < 0.001). During the clinical study, eight women experienced exacerbations of chronic cystitis (20%).Conclusion. Study results suggest that the drug Vesusten® may be an effective treatment for OAB in combination with chronic recurrent cystitis. Based on our findings, we believe that Vesusten® can be considered as a potential treatment option for patients with chronic cystitis.

#1927 Efficacy and safety of ripertamab in paediatic glomerular disease

Abstract Background and Aims Anti-B-cell treatment has been shown to be an efficient tactic for glomerular disease. Ripertamab as a novel anti-CD20 monoclonal antibody developed by China, has been structurally optimized to specifically bind to the transmembrane antigen CD20, with an amino acid difference in the constant region sequence compared to rituximab. This study reports the efficacy and safety of ripertamab in children with different glomerular diseases. Method We retrospectively report the data of 140 children with a diagnosis of glomerular disease and a treatment with ripertamab in a single center Results A total of 140 children (age, 11.2 ± 3.7 years; 58.6% boys) were included, 69/140 (49.3%) steroid-dependent nephrotic syndrome (SDNS), 38/140 (27.1%) steroid-resistant but CNIs-dependent nephrotic syndrome, 18/140 (12.9%) Lupus nephritis, 5/140 (3.6%) atypical hemolytic uremic syndrome, 4/140 (2.9%) ANCA associated vasculitis, 3/140 (2.1%) membranous nephropathy and 3/140 (2.1%) IgA vasculitis nephritis. The Median (IQR) duration of disease before the application of ripertamab was 4.4 (2.3, 7.4) years. They totally received 200 courses of ripertamab. A total of 83, 55, 1, and 1 patient received one, two, three, and four courses, respectively. Ripertamab 375 mg/m2 (maximum 500 mg) were injected per course. B cell depletion could be observed in 129/140 (92.1%) children one month after ripertamab. An additional course was administered due to recovery of B-cells or relapse. Median (IQR) follow-up was 0.8 (0.5, 1.1) years. The median relapse-free period after the first course was 4.7 months (IQR, 3.8, 5.6 months). Most of the relapses developed simultaneously with recovery of B-cells. About 36.7% of these children stopped steroid during the follow-up. One or more immunosuppressant (IS) drugs needed before ripertamab infusion could be withdrawn or reduced in 109/140 patients (77.9%). None of the patients developed life-threatening adverse events. Conclusion This study suggests that ripertamab could be an effective and safe treatment for various pediatric glomerular diseases.

Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication.

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.

Lymphomatoid papulosis. Case in pediatric dermatological clinical practice

A clinical case of lymphomatoid papulosis in a 10-year-old boy is described, clinically characterized by the presence of ulcerating nodes that resolve with the atrophy formation. The patient’s differential diagnostic workup included cutaneous anaplastic large cell lymphoma, cutaneous tuberculosis, polyarteritis nodosa, erythema nodosum, deep lupus erythematosus, and alpha-1 antitrypsin deficiency. Based on the history, clinical picture, as well as laboratory and instrumental studies, the patient was diagnosed with lymphomatoid papulosis. During the examination, no concomitant neoplastic diseases were identified in the patient. All elements resolved with the outcome being hyperpigmented spots and atrophy. To date, the relapse-free period of the disease in the patient is 10 months.

COMORBIDITY IN ONCOLOGY: MODERN CHALLENGES AND THE SEARCH FOR WAYS TO SOLVE THE PROBLEM

Introduction. The article is devoted to the current problem of modern oncology – increasing the treatment effectiveness of cancer patients with comorbidities. Comorbidity is accompanied by higher rates of mortality, disability, side effects of treatment, increased use of the patient's body resources, and lower quality of life. The aim of the study. To develop a method of recurrence prevention after bone lesions resection and bone replacement surgery for malignant primary bone tumors, which would ensure a longer duration of the 1st recurrence-free period in patients with comorbidities. Materials and methods. The study included a control group consisting of 27 patients who underwent bone replacement surgery after removal of primary malignant tumors of the pelvis and lower extremities. The study group included 25 patients who underwent biomin bone replacement surgery after removal of malignant primary tumors of the pelvic bones and lower limbs, as well as neuropeptide therapy with the drug dalargin. Results. The obtained data testify to the effectiveness of the proposed method of treatment with the use of dalargin: compaction of the structure of compact and spongy tissues and an increase in their heterogeneity have been established. Under the influence of dalargin, the structure of the interface, characteristic of intact bone tissue, is reorganized, accordingly, the restoration of strength is observed. 12 months after the operation, the bone density in the patients of the main group practically recovered to the values typical for the intact limb (p<0.01). No such recovery was observed in patients of the control group. Within 11 to 23 months, 10 patients of the control group had tumor recurrences. Instead, in the study group, the analysis of the results revealed the following: within 21 months, only 1 patient had a recurrence of the tumor. Conclusions. Neuropeptide Dalargin helps to increase the duration of the 1st relapse-free period in patients with primary malignant bone tumors with polymorbidity. The proposed treatment method with integration into the therapeutic protocol of the neuropeptide dalargin allows to increase the complex therapy effectiveness and improve the prognosis of the course of the disease.

Method for Determining Radioresistance of Cancer Cell Lines Based on Cluster Analysis of Clonogenic Cell Survival Data

Background: The outcome of radiation therapy, the duration and quality of life of cancer patients significantly depend on the radiosensitivity (RS) of a cancerous tumor, and the duration of the patient’s relapse-free period is largely determined by the degree of its radioresistance (RR). Today the results of molecular mechanism investigation of cancer radioresistance and the classification of cancer cells according to their radiophenotypes mostly contribute to improving prognosis methods of treatment outcomes and increasing effectiveness of radiation therapy. In this work, we developed a classification method of cancer cells according to their radiosensitivity using machine learning based on the data analysis of clonogenic cell survival under ionizing radiation. Material and methods: The method consists of clustering parameters of experimental dose-effect relationships, which were approximated using the equation of a linear-quadratic (LQ) model, which is used to evaluate RS of cancer cells in radiobiology. The training of the statistical model included published experimental dataset of 96 cancer cell lines, for which parameters a, b and their ratio a/b of the LQ model were determined. Classification of cancer cells according to their radiosensitivity was carried out based on principal component analysis (PCA) in the parameter space (a, a/b), k-means clustering and hierarchical clustering methods. Results: Application of the developed statistical model to a large dataset of cancer cells made it possible to reliably separate radiosensitive and radioresistant (RR) cells into two clusters according to the parameters a and a/b. Application of the model to cancer cells with acquired RR, in which RS was suppressed as a result of exposure to irradiation or hypoxia, allowed tracing the shift of parent cells’ parameters from the RS cluster to the RR cell cluster. To study the genetic mechanisms of radiosensitivity, we performed bioinformatic analysis of the mutation distribution in genes encoding proteins in the cellular signalling pathways of cancer cells, i.e. proliferation, apoptosis, repair of damaged DNA molecules and antioxidant defence cellular system. Conclusion: The developed statistical model of radiophenotypic classification of cancer cells based on their radiosensitivity can be used in the development of radiation therapy treatment plans taking into account radiosensitivity of patient’s tumour. The model may be also helpful in a joint analysis of the phenotypic and genotypic characteristics of cancer cells, aiming at the elucidation of the molecular and genetic mechanisms of radiosensitivity and development of biomarkers of radioresistance.

The role of surgical treatment of recurrent glioblastomas

Introduction. With standard treatment of glioblastoma, the vast majority of cases result in relapse of the disease, for which there is no consensus on the effectiveness of repeat resection. The lack of Level 1 evidence on the efficacy of surgical removal of recurrent glioblastomas (GB) indicates that the problem has not been resolved and stimulates interest in finding ways to combat this disease. Purpose. To study the effect of surgical treatment of a recurrent tumor on the overall life expectancy and post-relapse survival time of patients with glioblastomas. Materials and methods. The analysis was performed on data from 116 patients: 43 (37.1 %) women and 73 (62.9 %) men. The mean age at the time of diagnosis (primary surgery) was 52±12 full years. Surgical interventions were performed between 1999 and 2017. The study group included 50 patients who underwent GB resection. The control group consisted of 66 patients who were not operated on for GB. To achieve group homogeneity for all studied variables, the pseudo-randomization method was used. Statistical analysis was performed using the program SPSS Statistics 26.0. Results. The median overall life expectancy after GB resection was 23.6 [95 % CI=18.1–29.1] months, in the control group — 21.0 [95 % CI=12.8–29.2] months. The fatal outcome for the patients in the study group was simultaneously influenced by two characteristics: the duration of the relapse-free period (p=0.003) and the volume of the recurrent tumor (p=0.050). For the patients in the control group, only the duration of the relapse-free period (p <0.001) was impactful. The median post-relapse survival time was higher in those patients who underwent resection of 95 % or more of the GB volume than in those without surgery: 10.33 months [95 % CI 9.67 — NA months] and 6.33 months [95 % CI 5.07–11.2 months] (p<0.05), respectively. The 2‑year survival rate in the group after resection of 95 % or more of the GB volume is more than twice as high as in the non-operated group: 38.5 % and 13.7 %, respectively. Conclusions. Maximum reduction in GB volume appears to be advisable, especially in patients with a long relapse- free period when the formation is localized in the subdominant hemisphere of the brain, without spreading to the corpus callosum. Microsurgical removal of recurrent glioblastomas is an effective method of treating patients in comparison with conservative therapy.

Discontinuation of therapy in inflammatory bowel disease: Current views.

The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease (IBD). The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission. In patients with achieved long-term remission, the question of de-escalation or discontinuation of therapy arises, considering the possible side effects and economic burden of long-term therapy. For each of the drugs used in IBD (5-aminosalycaltes, immunomodulators, biological drugs, small molecules) there is a risk of relapse. Furthermore, studies show that more than 50% of patients who discontinue therapy will relapse. Based on the findings of large studies and meta-analysis, relapse of disease can be expected in about half of the patients after therapy withdrawal, in case of monotherapy with aminosalicylates, immunomodulators or biological therapy. However, longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor. It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking. Before making a decision on discontinuation of therapy, it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse. Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse. Several other predictive factors have also been identified, such as: High Crohn's disease activity index or Harvey Bradshaw index, younger age (< 40 years), longer disease duration (> 40 years), smoking, young age of disease onset, steroid use 6-12 months before cessation. An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs. The decision to discontinue therapy must be based on individual approach, taking into account the severity, extension, and duration of the disease, the possibility of side adverse effects, the risk of relapse, and patient's preferences.