Impact of Emergency Situations on the Level of Fear and Anxiety in Oncology Patients During Radiotherapy in a Developing Country.

OBJECTIVE: To analyze the level of fear and anxiety related to radiotherapy in oncology patients treated before and during the COVID-19 pandemic, as well as to examine whether the advancement of radiotherapy centers leads to any reduction in the patient's fear in emergency situations. METHODS: Two cross-sectional studies were conducted in two time frames (2016 and 2022) based on the analysis of the intensity of anxiety and fear of radiotherapy in oncology patients with assistance. A questionnaire for assessing fear of radiotherapy in oncology patients and Zung's and Beck's self-reported anxiety scales were used. The first part of the research integrated all data of research interest obtained from patients treated with radiotherapy during 2016, and the second cross-sectional study included all patients treated in 2022 during the COVID-19 pandemic. The study was prepared according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. RESULTS: The first cross-sectional study had 154 participants who had been treated with radiotherapy, while in the second study, there were 159 patients. Patients treated in 2022 show significantly higher levels of fear and anxiety. External beam radiotherapy and brachytherapy simultaneously used in both studies increased the level of fear and anxiety. CONCLUSION:  The conducted research showed exceptional differences in the intensity of fear and anxiety in patients treated with radiotherapy in different health situations, as was the case during the COVID-19 pandemic, with a significant impact on the stability of the health system and the challenges to providing standard services.

Five-year disease-free survival in FIGO IA stage endometrial cancer patients: Tertiary institution experience in a developing country.

Purpose: Endometrial cancer is characterized as histopathological, molecular, genetic, biological, and very diverse group of malignancies. Due to the need to precisely define the indications for adjuvant treatment in recent years, there has been a division made according to risk groups based on prognostic factors, which identify patients at risk for disease relapse, who may benefit from adjuvant therapy. The aim of this research was to examine the clinical and morphological factors that influence disease-free survival (DFS) and overall survival (OS) in patients with FIGO IA stage endometrial cancer. Material and methods: A retrospective clinical study was conducted, primarily based on the identification of factors that influence five-year DFS and OS. The study integrated data of FIGO IA stage endometrial cancer patients, who presented to gynecological oncology board for the first time after operative treatment, from January 1, 2016 to January 1, 2022. Adjuvant radiotherapy was applied to patients with an initially higher risk of disease progression. Length of survival was analyzed using Kaplan-Meier method, while log-rank test was used to assess differences between groups. Results: The results show that 5-year OS for 93 patients was 89.2% and DFS was 88.2%. Application of adjuvant brachytherapy, number of deliveries, MRI staging, type of institution where the surgery was performed influenced DFS. Pathohistological characteristics of tumor indicated a statistically significant impact on DFS. Conclusions: Application of adjuvant brachytherapy in high-intermediate and high-risk patients contributes to DFS increase. Moreover, the existence of a pre-operative MRI assessment of the stage of disease as well as the type of healthcare provided by an institution where the surgery was performed, significantly affect DFS.

Secondary Breast Malignancy from Renal Cell Carcinoma: Challenges in Diagnosis and Treatment-Case Report.

Renal cell carcinoma represents about 2% of all malignant tumours in adults. Metastases of the primary tumour in the breast make up to about 0.5-2% of the cases. Renal cell carcinoma metastases in the breast are extremely rare and have been sporadically recorded in the literature. In this paper, we present the case of a patient with breast metastasis of renal cell carcinoma 11 years after primary treatment. Case presentation: An 82-year-old female who had right nephrectomy due to renal cancer in 2010 felt a lump in her right breast in August 2021, whereby a clinical examination revealed a tumour at the junction of the upper quadrants of her right breast, about 2 cm, movable toward the base, vaguely limited, and with a rough surface. The axillae were without palpable lymph nodes. Mammography showed a circular and relatively clearly contoured lesion in the right breast. Ultrasound showed an oval lobulated lesion of 19 × 18 mm at the upper quadrants, with strong vascularisation and without posterior acoustic phenomena. A core needle biopsy was performed, and the histopathological findings and obtained immunophenotype indicated a metastatic clear cell carcinoma of renal origin. A metastasectomy was performed. Histopathologically, the tumour was without desmoplastic stroma, comprising predominantly solid-type alveolar arrangements of large moderately polymorphic cells, bright and abundant cytoplasm, and round vesicular cores with focally prominent nuclei. Immunohistochemically, tumour cells were diffusely positive for CD10, EMA, and vimentin, and negative for CK7, TTF-1, renal cell antigen, and E-cadherin. With a normal postoperative course, the patient was discharged on the third postoperative day. After 17 months, there were no new signs of the underlying disease spreading at regular follow-ups. Conclusion: Metastatic involvement of the breast is relatively rare and should be suspected in patients with a prior history of other cancers. Core needle biopsy and pathohistological analysis are required for the diagnosis of breast tumours.

Review of compounds that exhibit radioprotective and/or mitigatory effects after application of diagnostic or therapeutic ionizing radiation.

PURPOSE: Exposure to ionizing radiation can be accidental or for medical purposes. Analyzes of the frequency of radiation damage in the general population, it has been determined that by far the most common are those that occur as a result of diagnostic or therapeutic procedures. Damage caused by radiation, either accidentally or for therapeutic purposes, can be reduced by the use of radioprotectors, mitigators or other therapeutic agents. A detailed research of the available literature shows that there is little systematized data of potentially radioprotective and/or mitigating effects of drugs from the personal therapy of patients during the application of therapeutic ionizing radiation. The aim of this paper is to present review of compounds, especially personal therapy drugs, that exhibit radioprotective and/or mitigating effects after the application of diagnostic or therapeutic ionizing radiation. CONCLUSIONS: Given the widespread use of ionizing radiation for diagnostic and therapeutic purposes, there is a clear need to create a strategy and recommendations of relevant institutions for the use of radioprotectors and mitigators in everyday clinical practice, with individual evaluation of the patient's condition and selection of the compounds that will show the greatest benefit in terms of radioprotection.

Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience.

Introduction: Peptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment. Methodology: We retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups. Results: A total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively. Conclusion: The study's results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly.

Acute chemoradiotherapy toxicity in cervical cancer patients.

During radiotherapy treatment for cervical cancer, up to 84% of patients exhibit some form of acute radiation toxicity (ART). The primary aim of this clinical study is to determine the impact of angiotensin-converting enzyme (ACE) inhibitors, ß-blockers and other risk factors such as the patient's anatomical characteristics on ART emergence in patients with locally advanced cervical cancer treated by chemoradiotherapy. This is a combination of two nested case-control studies within the cohort of patients with locally advanced cervical cancer based on the analysis of potential risk factors for the onset of ART in patients treated with 3D conformal radiotherapy (3D-CRT) and 2D conventional radiotherapy (2D-RT), prospectively followed up from January 2017 to September 2018 in a tertiary care hospital. The ACE inhibitors and bladder volume were identified as factors that significantly affect the occurrence of ART in patients treated with 3D-CRT. In patients treated with 2D-RT, the factors that significantly affect the occurrence of ART were ACE inhibitors, body mass index (BMI), brachytherapy rectal and bladder dose. This study has shown that BMI, radiation dose received by the bladder and rectum are of exceptional importance for the occurrence of the ART and also that therapy with ACE inhibitors was associated with the decreased chances of the ART.

Analysis of postoperative radiotherapy effects within risk groups in patients with FIGO I, II, and III endometrial cancer.

INTRODUCTION: To define indications for adjuvant radiotherapy in patients with endometrial cancer, the risk groups have been established according to clinical and pathological prognostic factors. The purpose was to determine precise criteria for adjuvant radiotherapy and identify patients with increased risk for disease relapse who may benefit from postoperative radiotherapy, with an acceptable level of toxicity. MATERIALS AND METHODS: A retrospective study was conducted at the Department of Oncology and Radiology, Kragujevac, during a 5-year period. A group of 80 patients with endometrial cancer treated with adjuvant radiotherapy were included in the study. Patients were divided into four risk groups according to ESMO-ESGO-ESTRO Consensus Conference classification. The Kaplan-Meier method was used for overall and progression-free survival. A statistical analysis was performed using SPSS 20.0 statistical software. RESULTS: The 5-year survival rate was 80%, and 66.3% patients were progression-free during this period. Fatal outcome occurred in 20% of patients. The results showed survival was shortest in patients from the high-risk group. Factors that had impact on the 5-year survival were comorbidities, FIGO stage, postoperative radiotherapy, organ site of late toxicity, and localization of metastases. The analysis of postoperative radiotherapy effects showed that 72.5% of patients had no complications. The most common symptoms of late irradiation toxicity arose from the gastrointestinal tract. Toxicity was usually moderate. CONCLUSIONS: Adjuvant radiotherapy can potentially prolong survival and prevent recurrence, with acceptable level of toxicity, to preserve patient's quality of life. Patient classification into appropriate risk groups allows for adjuvant treatment individualization.

Mesenchymal stem cells attenuate liver fibrosis by suppressing Th17 cells - an experimental study.

This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSC)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl4 (1 µl/g intraperitoneally) twice/week for 1 month. MSCs (1 × 106 ), or MSC-conditioned medium (MSC-CM), were intravenously injected 24 h after CCl4 and on every 7th day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining, and RT-PCR. Serum levels of cytokines, indoleamine 2,3-dioxygenase (IDO), and kynurenine were determined by ELISA. Flow cytometry was performed to identify liver-infiltrated cells. In vitro, CD4+ T cells were stimulated and cultured with MSCs. 1-methyltryptophan was used for inhibition of IDO. MSCs significantly attenuated CCl4 -induced liver fibrosis by decreasing serum levels of inflammatory IL-17, increasing immunosuppressive IL-10, IDO, and kynurenine, reducing number of IL-17 producing Th17 cells, and increasing percentage of CD4+ IL-10+ T cells. Injection of MSC-CM resulted with attenuated fibrosis accompanied with the reduced number of Th17 cells in the liver and decreased serum levels of IL-17. MSC-CM promoted expansion of CD4+ FoxP3+ IL-10+ T regulatory cells and suppressed proliferation of Th17 cells. This phenomenon was completely abrogated in the presence of IDO inhibitor. MSCs, in IDO-dependent manner, suppress liver Th17 cells which lead to the attenuation of liver fibrosis.

Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells.

Mesenchymal stem cells (MSCs) are, due to immunomodulatory characteristics, considered as novel agents in the treatment of immune-mediated acute liver failure. Although it is known that MSCs can regulate activation of T lymphocytes, their capacity to modulate function of neutrophils and natural killer T (NKT) cells, major interleukin (IL) 17-producing cells in acute liver injury, is still unknown. By using 2 well-established murine models of neutrophil and NKT cell-mediated acute liver failure (induced by carbon tetrachloride and α-galactoceramide), we investigated molecular and cellular mechanisms involved in MSC-mediated modulation of IL17 signaling during acute liver injury. Single intravenous injection of MSCs attenuate acute hepatitis and hepatotoxicity of NKT cells in a paracrine, indoleamine 2,3-dioxygenase (IDO)-dependent manner. Decreased levels of inflammatory IL17 and increased levels of immunosuppressive IL10 in serum, reduced number of interleukin 17-producing natural killer T (NKT17) cells, and increased presence of forkhead box P3 + IL10-producing natural killer T regulatory cells (NKTregs) were noticed in the injured livers of MSC-treated mice. MSCs did not significantly alter the total number of IL17-producing neutrophils, CD4+, and CD8 + T lymphocytes in the injured livers. Injection of mesenchymal stem cell-conditioned medium (MSC-CM) resulted with an increased NKTreg/NKT17 ratio in the liver and attenuated hepatitis in vivo and significantly reduced hepatotoxicity of NKT cells in vitro. This phenomenon was completely abrogated in the presence of IDO inhibitor, 1-methyltryptophan. In conclusion, the capacity of MSCs to alter NKT17/NKTreg ratio and suppress hepatotoxicity of NKT cells in an IDO-dependent manner may be used as a new therapeutic approach in IL17-driven liver inflammation. Liver Transplantation 23 1040-1050 2017 AASLD.