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In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1ß, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.
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Doença Hepática Induzida por Substâncias e Drogas , Ratos , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Peróxido de Hidrogênio , Tetracloreto de Carbono/toxicidade , Antioxidantes/metabolismoRESUMO
BACKGROUND: Isolated splenic metastases from endometrial cancer, which is a relatively common malignancy, are extremely rare findings; to date, only 14 cases have been reported in the literature. CASE SUMMARY: We report a patient with isolated splenic metastases of endometrial cancer 3 years after radical surgery of the primary tumor. The patient was successfully treated by splenectomy and six cycles of paclitaxel. Fifty months after splenectomy, she was alive and well, and with no evidence of disease. CONCLUSION: Isolated spleen metastasis of endometrial cancer is very rare. Radical surgery and adjuvant therapy may offer excellent long-term survival.
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Neoplasias do Endométrio , Segunda Neoplasia Primária , Neoplasias Esplênicas , Neoplasias do Endométrio/patologia , Feminino , Humanos , Esplenectomia , Neoplasias Esplênicas/secundário , Neoplasias Esplênicas/cirurgiaRESUMO
PURPOSE: The objective of the study is to describe QoL in women who have undergone surgical treatment for breast cancer (BC). The focus of the description is the differences in QoL between women treated by modified radical mastectomy (MRM) and women who underwent breast-conserving surgery (BCS) at the Breast and Endocrine Surgery Department of the Clinical Center of Nis, Serbia. METHOD: From January 1, 2014, until December 31, 2017, 300 patients were treated with BCS and 300 patients with MRM. To assess the QOL, a total of 600 BC patients completed the WHOQOL-BREF questionnaires. The results were analyzed using the t test and chi-square test. WHOQOL produces a quality of life profile. It derives four domain scores: physical health, psychological, social relationships, and environment. Social and demographic factors (age, education, marital status) were collected in both groups. RESULT: In all four domains, patients treated with conserving surgeries scored higher than patients treated with radical mastectomy. This result was controlled for a set of demographic variables. The differences in QoL scores are present on all levels of controlling variables. CONCLUSION: According to the results of this study, the QoL in women after an MRM is significantly lower than the QoL in women after BCS. It is especially true for the environment domain. Conserving surgery should be recommended and specific, and patient-centered interventions for increasing QoL of the patients who opted for radical mastectomy should be designed. The intervention should focus on social and environmental domains.
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Neoplasias da Mama/psicologia , Neoplasias da Mama/cirurgia , Mastectomia/métodos , Qualidade de Vida/psicologia , Adulto , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: In order to enhance the prognostic benefit of new molecular markers, the aim of this study was to identify possible association of axillary lymph node (ALN) status and pN with clinicopathological characteristics and expression of EZH2 and CD44 in invasive ductal carcinoma (IDC) of the breast. METHODS: The investigation included 106 patients with IDC who had undergone radical mastectomy at the Clinic of Endocrine Surgery in Nis. Clinicopathologic parameters and immunohistochemical expression of EZH2 and CD44 in primary IDC were investigated in relation to ALN status and pN. RESULTS: Our univariate analysis established that T3-T4 stage, high EZH2, and high EZH2 with ER- were associated with ALN metastasis (p=0.014; 0.003; 0.013). Decreased probability for ALN involvement was found with T1 stage, and low EZH2 with ER+ (p=0.032; 0.022). Multivariant analysis established that high EZH2 in cancer cells was associated with high risk for ALN metastases (p=0.004); T1 tumors were associated with low risk (p=0.037). Higher pN was associated with high EZH2, high EZH2 with ER-, as well as an advanced clinical and disease stage (p=0.006; 0.001; p=0.002, 0.001). Lower pN was associated with ER+, and ER+ with low EZH2 (p= 0.004; 0.012). CD44 was not associated with ALN involvement, nor with pN. CONCLUSIONS: This study revealed association of EZH2 with ALN metastases, where disease stage and expression profiles of EZH2 and ER may have affected regional pN.
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OBJECTIVE: The aim of our study was to find the best model with sufficient power to improve the risk stratification in major vascular surgery patients during the first 30 days after this procedure. The discriminatory power of 4 biomarkers (troponin I [TnI], N-terminal prohormone of brain natriuretic peptide [NT-proBNP], creatine kinase-MB isoenzyme [CK-MB], high-sensitivity C-reactive protein [hs-CRP]) was tested as well as 2 risk assessment models and 13 different combinations of them. SUBJECTS AND METHODS: The study included 122 patients (77% men, 23% women) with an average age of 67.03 ± 4.5 years. An aortobifemoral bypass was performed in 6.56% of the patients, a femoropopliteal bypass in 18.85%, and 49.18% received open surgical reconstruction of the carotid arteries. A total of 25.41% of the patients were given an aortobi-iliac bypass. RESULTS: During the first 30 days, 13 patients (10.7%) had 17 cardiac complications. The most common complication was the new onset of atrial fibrillation (35.3%). During the first 10 days, 10 patients had 1 complication and 2 patients had 2 cardiac events, while 1 patient had 3 complications. By comparing combinations of scores and markers, it was shown that revised cardiac risk index (RCRI) + Vascular Portsmouth Physiological and Operative Severity Score (V-POSSUM) + hsTnI and RCRI + V-POSSUM + hsTnI + NT-proBNP with 100% sensitivity, > 80% specificity had the best discriminatory ability (AUC 0.924 and 0.933, respectively; p < 0.001 for both models) for cardiac complications during the 30 days after surgery. CONCLUSION: Combinations of traditional preoperative risk factors and scores can enhance the assessment of major adverse cardiac events (MACE) in patients preparing for large vascular surgery. Using only one risk score in these patients seems to be underperforming in preoperative risk assessment.
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Biomarcadores/sangue , Cardiopatias/epidemiologia , Medição de Risco/métodos , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Creatina Quinase Forma MB/sangue , Feminino , Cardiopatias/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Curva ROC , Fatores de Risco , Sérvia/epidemiologia , Tempo , Troponina I/sangueRESUMO
INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is an extensively used simple risk stratification tool advocated by the European Society of Cardiology and European Society of Anesthesiology (ESC/ESA). PURPOSE: The aim of this study was to find the best model for predicting 3-month cardiovascular complications in elective major vascular surgical patients using preoperative clinical assessment, calculation of the RCRI and Vascular Physiological and Operative Severity Score for the enumeration of mortality and morbidity (V-POSSUM) scores, and the preoperative levels of N-terminal brain natriuretic peptide (NT pro-BNP), high-sensitivity troponin I (hs TnI), and high-sensitivity C-reactive protein (hs CRP). MATERIALS AND METHODS: We included 122 participants in a prospective, single-center, observational study. The levels of NT pro-BNP, hs CRP, and hs TnI were measured 48 hours prior to surgery. During the perioperative period and 90 days after surgery the following adverse cardiac events were recorded: myocardial infarction, arrhythmias, pulmonary edema, acute decompensated heart failure, and cardiac arrest. RESULTS: During the first 3 months after surgery 29 participants (23.8%) had 50 cardiac complications. There was a statistically significant difference in the RCRI score between participants with and without cardiac complications. ROC analysis showed that a combination of RCRI with hs TnI has good discriminatory power (AUC 0.909, p<0,001). By adding NT pro-BNP concentrations to the RCRI+hs TnI+V-POSSSUM combination we obtained the model with the best predictive power for 3-month cardiac complications (AUC 0.963, p<0,001). CONCLUSION: We need to improve preoperative risk assessment in participants scheduled for major vascular surgery by combining their clinical scores with biomarkers. Therefore, it is possible to identify patients at risk of cardiovascular complications who need adequate preoperative diagnosis and treatment.
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Medição de Risco , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Biomarcadores , Proteína C-Reativa/análise , Procedimentos Cirúrgicos Eletivos , Feminino , Cardiopatias , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de RiscoRESUMO
PURPOSE: The purpose of this study was to determinate disease-free interval (DFI) and overall survival (OS) in HER2-positive breast cancer patients who received adjuvant trastuzumab at the University Clinic of Nis, Serbia, and to investigate the influence of clinicopathological and biological characteristics of the tumor on prognosis. The second aim was to determinate the most frequent cause for the treatment discontinuation, recurrence rate, as well as the site of most common localization of the first recurrence of disease. METHODS: This research was conducted as a retrospective study at the University Oncology Clinic, Clinical Centre in Nis. The study included 238 patients who were operated and treated for HER2-positive breast cancer between January 1st, 2007 to September 30th, 2012 and followed up until December 31st, 2016. Trastuzumab was administered concurrently with taxanes, if administered, or after the completed anthracycline-based chemotherapy. RESULTS: After a median follow up of 69 months the 5-year DFI was 65.9% and 5-year OS was 81.8% and, as expected, significantly longer in the group of patients with smaller tumors, a smaller number of positive axillary lymph nodes, as well as a lower stage of disease (p<0.0001). Patients older than 65 years had a longer DFI compared to the 45-65 and under 45 age groups of patients (p=0.01). No statistical significance was found in the length of DFI in relation to the histological tumor subtype, tumor grade, or the status of hormone receptors. Unlike DFI, a longer OS was recorded in the group of patients with lower tumor grade (p=0.03) and there was no statistically significant difference in survival regarding the age of patients (p=0.07). Recurrence occurred in approximately one third of the patients (38.23%), mostly in the form of local recurrence. Adjuvant therapy with trastuzumab was not completely carried out in 18.49% of the patients, the most common reason being the progression of disease. CONCLUSIONS: A long median follow up period of 69 months indicated that anti-HER2 monoclonal antibody trastuzumab, after anthracycline-based chemotherapy or concurrently with taxanes, is efficient and safe in treating early breast cancer.
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Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor ErbB-2/genética , Estudos Retrospectivos , Sérvia/epidemiologia , Taxoides/uso terapêuticoRESUMO
PURPOSE: The clinical behavior and outcome of multifocal (MF) and multicentric (MC) breast tumors are not well characterized. The purpose of this study was to compare the prognosis of MF/MC tumors with unifocal (UF)tumors and its correlation with other pathological characteristics and patient outcomes. METHODS: Eighty-three patients with MC/MF breast cancer and 501 with UF breast cancer treated at the Surgical Clinic Nis were studied. We compared MC/MF and UF breast cancer patients with respect to demographics, tumor characteristics- adjuvant systemic therapy, local recurrence-free survival (LRFS) and overall survival (OS). RESULTS: There was no significant statistical difference between the two groups with respect to mean age at diagnosis, tumor grade, nodal status, estrogen receptor status, lymphovascular invasion (LVI) and adjuvant systemic therapy. The MC/MF group had more patients with modified radical mastectomy and the UF group had more patients with breast-conserving surgery. Cox multivariate regression analysis showed that the regional lymph node metastases and LVI were the most important predictors of 5-year OS rate. During this period, locoregional recurrence was registered in 29 (5.78%) patients in the UF group and in 5 (6.02%) patients in the MF/MC group (p=0.48). No statistically significant differences in the 5-year LRFS and OS between the two groups were noticed. CONCLUSION: The prognostic value of MF/MC disease is still not well known, although some studies have suggested that it is associated with a worse prognosis. This study showed no statistically significant difference in the 5-year LRFS and OS between UF and MF/MC groups.
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Neoplasias da Mama/patologia , Adulto , Idoso , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
Perforation represents a rare and severe complication of gastric cancer (GC) with a large hospital mortality (8-82%). The aim of this study is to evaluate the clinical-pathological features in patients with perforated gastric cancer (PGC) and to advise the surgical treatment options. A total of 11 patients with PGC were retrospectively reviewed among 376 consecutive cases of GC operated. The clinical-pathological features including tumor stage, survival, and the type of treatment were observed. The perforation was more frequent in stage III (8 patients) and in stage IV (3 patients), but none of the cases in stage I and II GC were observed. All the patients had serosal invasion and lymph node metastasis. Limited lymphadenectomy (D0, D1) was performed in 5 patients, and extended lymphadenectomy (D2, D3) in 3 patients. Emergency gastrectomy was performed in 8 (72.8%) patients, subtotal gastrectomy in 5 (45.5%), and total gastrectomy in 3 (27.2%) cases. Three (27.2%) patients were treated by simple closure with omental patch. The overall 30-day mortality rate was 46%. The survival rate was higher among the patients who underwent curative resection (75.77±68.88 days) than in those who underwent simple closure with omental patch (18.00±24.43 days). The difference between the treatments in these groups was significant (p < 0.05). PGC required surgical emergency. Curative resection improved long-term survival in the patients with potentially curable gastric malignancy. Unsuccessful outcomes after PGC could be attributed to the poor condition of the patients and the advanced disease stage.