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Browsing by Author "Dimitrijevic, Ivan (59595303500)"

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    Can preoperative CEA and CA19-9 serum concentrations suggest metastatic disease in colorectal cancer patients?
    (2017)
    Lalosevic, Milica Stojkovic (57218133245)
    ;
    Stankovic, Sanja (7005216636)
    ;
    Stojkovic, Mirjana (58776160500)
    ;
    Markovic, Velimir (57206490091)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Lalosevic, Jovan (57190969635)
    ;
    Petrovic, Jelena (57207943674)
    ;
    Brankovic, Marija (57217208566)
    ;
    Markovic, Aleksandra Pavlovic (24438035400)
    ;
    Krivokapic, Zoran (55503352000)
    Objective: This study was designed to investigate the efficiency of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate cancer antigen (CA19-9) levels for diagnosing synchronous liver metastases and lymph node in colorectal carcinoma (CRC) patients. Subjects and Methods: A total of 300 patients with histologically diagnosed CRC were included in this study between May 2014 and March 2015. The data were obtained from patient's medical records: medical history, demographics, tumor location, differentiation (grade), depth of the tumor (T), lymph node metastases (N), distant metastases (M), lymphatics, venous and perineural invasion, and disease stage. Tumor markers were measured with an electrochemilu-minescent assay and the reference value was 5ng/ml for CEA and for Ca 19-9, 37u/ml. Results: There was A high statistically significant difference in the levels of serum CEA and CA19-9 between different disease stages of CRC (P<0.001). Regarding different T stages of CRC, We noticed a significant statistical difference in CEA (stage I 3.76±8.73; II 5.68±17.27, III 7.56±14.81, and IV 70.90±253.23) and CA 19-9 levels (stage I 9.65 ±11.03, II 9.83±11.09; III 19.58±36.91, and IV 228.9±985.38, respectively). The mean CEA and CA19-9 serum levels were significantly higher in patients with regional lymph nodes involvement (CEA 37.21 ±177.85 vs 4.79±9.90, CA19-9 119.51 ±687.71 VS 12.24±17.69, respectively, P<0.05) and in liver metastases (CEA 86.56± 277.65 vs. 5.98± 12.98, and CA19-9 273.27±1073.46 vs. 4.98± 3142, respectively, with P<0.001) in comparison to patients without lymph node involvement and liver metastases. We noticed a cut-off value for lymph nodes involvement, for CEA and CA 19-9, 3.5 ng/mL and 7.5 U/mL, respectively. While, a cut-off value for the presence of synchronous liver metastases of these two markers was 3.5 ng/mL AND 5.5 U/mL. Conclusion: Our study showed that tumor makers, CEA and CA19-9, can be used as diagnostic factors regarding the severity of CRC specifically to suggest metastatic disease in CRC.
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    Cell-free DNA as biomarker and source for mutation detection in primary colorectal cancer
    (2017)
    Nikolic, Aleksandra (57194842918)
    ;
    Vlajnic, Marina (57194184351)
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    Ristanovic, Momcilo (56357953700)
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    Petrovic, Jelena (57207943674)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Krivokapic, Zoran (55503352000)
    ;
    Radojkovic, Dragica (6602844151)
    Purpose: To analyze if cell-free (cf)DNA levels and the presence of KRAS and BRAF mutations in serum could be used as diagnostic biomarkers in patients with primary colorectal cancer (CRC). Methods: This study included 92 individuals who were operated due to primary CRC (N=52;study group) and to hemorrhoids (N=40;control group). Serum cfDNA levels were measured with real-time PCR (RT-PCR) using PicoGreen dsDNA quantitation reagent. Colorectal tissue and related blood and serum samples taken at the time of surgery were subjected to DNA extraction and analysis of KRAS and BRAF mutations based on multiplex SNaPshot assay and DNA sequencing. Results: The average cfDNA concentration was lower in patients of the study group (20±7 ng/μL) in comparison to controls (34±9 ng/μL) and this difference was statistically significant (p<0.001). The SNaPshot analysis detected KRAS c35 mutations in colorectal tumor tissue in 14 cases, but the presence of the mutation was not confirmed in cfDNA extracted from blood samples of these patients. Conclusions: The level of serum cfDNA in CRC is decreased in comparison to patients with hemorrhoids, which questions the usefulness of cfDNA as cancer biomarker. Also, cfDNA does not appear to be suitable as a source for mutation detection in this disease.
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    Cell-free DNA as biomarker and source for mutation detection in primary colorectal cancer
    (2017)
    Nikolic, Aleksandra (57194842918)
    ;
    Vlajnic, Marina (57194184351)
    ;
    Ristanovic, Momcilo (56357953700)
    ;
    Petrovic, Jelena (57207943674)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Krivokapic, Zoran (55503352000)
    ;
    Radojkovic, Dragica (6602844151)
    Purpose: To analyze if cell-free (cf)DNA levels and the presence of KRAS and BRAF mutations in serum could be used as diagnostic biomarkers in patients with primary colorectal cancer (CRC). Methods: This study included 92 individuals who were operated due to primary CRC (N=52;study group) and to hemorrhoids (N=40;control group). Serum cfDNA levels were measured with real-time PCR (RT-PCR) using PicoGreen dsDNA quantitation reagent. Colorectal tissue and related blood and serum samples taken at the time of surgery were subjected to DNA extraction and analysis of KRAS and BRAF mutations based on multiplex SNaPshot assay and DNA sequencing. Results: The average cfDNA concentration was lower in patients of the study group (20±7 ng/μL) in comparison to controls (34±9 ng/μL) and this difference was statistically significant (p<0.001). The SNaPshot analysis detected KRAS c35 mutations in colorectal tumor tissue in 14 cases, but the presence of the mutation was not confirmed in cfDNA extracted from blood samples of these patients. Conclusions: The level of serum cfDNA in CRC is decreased in comparison to patients with hemorrhoids, which questions the usefulness of cfDNA as cancer biomarker. Also, cfDNA does not appear to be suitable as a source for mutation detection in this disease.
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    Combined Diagnostic Efficacy of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Mean Platelet Volume (MPV) as Biomarkers of Systemic Inflammation in the Diagnosis of Colorectal Cancer
    (2019)
    Stojkovic Lalosevic, Milica (57218133245)
    ;
    Pavlovic Markovic, Aleksandra (55110483700)
    ;
    Stankovic, Sanja (7005216636)
    ;
    Stojkovic, Mirjana (58776160500)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Radoman Vujacic, Irena (57206897292)
    ;
    Lalic, Daria (57206903158)
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    Milovanovic, Tamara (55695651200)
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    Dumic, Igor (57200701725)
    ;
    Krivokapic, Zoran (55503352000)
    Background: Systemic inflammation in colorectal cancer (CRC) may be reflected by neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV). This study was designed to investigate the efficiency of preoperative NLR, PLR, and MVP as a tool for the assessment of tumor characteristics in newly diagnosed patients with CRC. Patients and Methods: For 300 patients and 300 healthy volunteers, complete blood counts with automated differential counts were performed. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; PLR was calculated by dividing the absolute platelet count by the absolute lymphocyte count. The diagnostic performance of NLR, PLR, and MVP was estimated by ROC curve. Results: ROC curve analysis showed high diagnostic efficacy of NLR and PLR in CRC patients with cut-off values of 2.15 (AUC = 0.790, 95% CI 0.736-0.884, Se = 74.1%, and Sp = 73%) and 123 (AUC = 0.846, 95% CI 0.801-0.891, Se = 73.5%, and Sp = 80%) compared to healthy controls, respectively. The diagnostic efficacy of three combined markers was superior compared with individual markers (AUC = 0.904, 95% CI 0.812-0.989, Se = 96%, and Sp = 70%). Conclusion: NRL, PLR, and MPV may be useful markers in diagnostic and early recognition of different stages of CRC; additionally combined all together have stronger diagnostic efficacy.
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    Combined diagnostic efficacy of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) as biomarkers of systemic inflammation in the diagnosis of colorectal cancer
    (2019)
    Lalosevic, Milica Stojkovic (57218133245)
    ;
    Markovic, Aleksandra Pavlovic (24438035400)
    ;
    Stankovic, Sanja (7005216636)
    ;
    Stojkovic, Mirjana (58776160500)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Vujacic, Irena Radoman (57208718001)
    ;
    Lalic, Daria (57206903158)
    ;
    Milovanovic, Tamara (55695651200)
    ;
    Dumic, Igor (57212525843)
    ;
    Krivokapic, Zoran (55503352000)
    Background. Systemic inflammation in colorectal cancer (CRC) may be reflected by neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV). This study was designed to investigate the efficiency of preoperative NLR, PLR, and MVP as a tool for the assessment of tumor characteristics in newly diagnosed patients with CRC. Patients and Methods. For 300 patients and 300 healthy volunteers, complete blood counts with automated differential counts were performed. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; PLR was calculated by dividing the absolute platelet count by the absolute lymphocyte count. The diagnostic performance of NLR, PLR, and MVP was estimated by ROC curve. Results. ROC curve analysis showed high diagnostic efficacy of NLR and PLR in CRC patients with cut-off values of 2.15 (AUC = 0 790, 95% CI 0.736-0.884, Se = 74 1%, and Sp = 73%) and 123 (AUC = 0 846, 95% CI 0.801-0.891, Se = 73 5%, and Sp = 80%) compared to healthy controls, respectively. The diagnostic efficacy of three combined markers was superior compared with individual markers (AUC = 0 904, 95% CI 0.812-0.989, Se = 96%, and Sp = 70%). Conclusion. NRL, PLR, and MPV may be useful markers in diagnostic and early recognition of different stages of CRC; additionally combined all together have stronger diagnostic efficacy. © 2019 Milica Stojkovic Lalosevic et al.
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    Combined diagnostic efficacy of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) as biomarkers of systemic inflammation in the diagnosis of colorectal cancer
    (2019)
    Lalosevic, Milica Stojkovic (57218133245)
    ;
    Markovic, Aleksandra Pavlovic (24438035400)
    ;
    Stankovic, Sanja (7005216636)
    ;
    Stojkovic, Mirjana (58776160500)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Vujacic, Irena Radoman (57208718001)
    ;
    Lalic, Daria (57206903158)
    ;
    Milovanovic, Tamara (55695651200)
    ;
    Dumic, Igor (57212525843)
    ;
    Krivokapic, Zoran (55503352000)
    Background. Systemic inflammation in colorectal cancer (CRC) may be reflected by neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV). This study was designed to investigate the efficiency of preoperative NLR, PLR, and MVP as a tool for the assessment of tumor characteristics in newly diagnosed patients with CRC. Patients and Methods. For 300 patients and 300 healthy volunteers, complete blood counts with automated differential counts were performed. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; PLR was calculated by dividing the absolute platelet count by the absolute lymphocyte count. The diagnostic performance of NLR, PLR, and MVP was estimated by ROC curve. Results. ROC curve analysis showed high diagnostic efficacy of NLR and PLR in CRC patients with cut-off values of 2.15 (AUC = 0 790, 95% CI 0.736-0.884, Se = 74 1%, and Sp = 73%) and 123 (AUC = 0 846, 95% CI 0.801-0.891, Se = 73 5%, and Sp = 80%) compared to healthy controls, respectively. The diagnostic efficacy of three combined markers was superior compared with individual markers (AUC = 0 904, 95% CI 0.812-0.989, Se = 96%, and Sp = 70%). Conclusion. NRL, PLR, and MPV may be useful markers in diagnostic and early recognition of different stages of CRC; additionally combined all together have stronger diagnostic efficacy. © 2019 Milica Stojkovic Lalosevic et al.
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    Combined Diagnostic Efficacy of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Mean Platelet Volume (MPV) as Biomarkers of Systemic Inflammation in the Diagnosis of Colorectal Cancer
    (2019)
    Stojkovic Lalosevic, Milica (57218133245)
    ;
    Pavlovic Markovic, Aleksandra (55110483700)
    ;
    Stankovic, Sanja (7005216636)
    ;
    Stojkovic, Mirjana (58776160500)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Radoman Vujacic, Irena (57206897292)
    ;
    Lalic, Daria (57206903158)
    ;
    Milovanovic, Tamara (55695651200)
    ;
    Dumic, Igor (57200701725)
    ;
    Krivokapic, Zoran (55503352000)
    Background: Systemic inflammation in colorectal cancer (CRC) may be reflected by neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV). This study was designed to investigate the efficiency of preoperative NLR, PLR, and MVP as a tool for the assessment of tumor characteristics in newly diagnosed patients with CRC. Patients and Methods: For 300 patients and 300 healthy volunteers, complete blood counts with automated differential counts were performed. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; PLR was calculated by dividing the absolute platelet count by the absolute lymphocyte count. The diagnostic performance of NLR, PLR, and MVP was estimated by ROC curve. Results: ROC curve analysis showed high diagnostic efficacy of NLR and PLR in CRC patients with cut-off values of 2.15 (AUC = 0.790, 95% CI 0.736-0.884, Se = 74.1%, and Sp = 73%) and 123 (AUC = 0.846, 95% CI 0.801-0.891, Se = 73.5%, and Sp = 80%) compared to healthy controls, respectively. The diagnostic efficacy of three combined markers was superior compared with individual markers (AUC = 0.904, 95% CI 0.812-0.989, Se = 96%, and Sp = 70%). Conclusion: NRL, PLR, and MPV may be useful markers in diagnostic and early recognition of different stages of CRC; additionally combined all together have stronger diagnostic efficacy.
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    Current trends in clinical genetics of colorectal cancer
    (2016)
    Markovic, Srdjan (57210721043)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Zogovic, Branimir (54404258600)
    ;
    Markovic, Velimir (57206490091)
    ;
    Barisic, Goran (55996920300)
    ;
    Krivokapic, Zoran (55503352000)
    Recent innovations in molecular biology and colorectal cancer (CRC) genetics have facilitated the understanding of the pathogenesis of sporadic and hereditary CRC syndromes. The development of technology has enabled data collection for a number of genetic factors, which lead to understanding of the molecular mechanisms underlying CRC. The incidence and the nature of CRC is a mixture of genetic and environmental factors. The current field of interest is to understand how molecular basis could shape predisposition for developing CRC, disease progression and response to chemotherapy. In this article, we summarize new and developing genetic markers, and assess their clinical value for inherited and sporadic CRC.
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    Current trends in clinical genetics of colorectal cancer
    (2016)
    Markovic, Srdjan (57210721043)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Zogovic, Branimir (54404258600)
    ;
    Markovic, Velimir (57206490091)
    ;
    Barisic, Goran (55996920300)
    ;
    Krivokapic, Zoran (55503352000)
    Recent innovations in molecular biology and colorectal cancer (CRC) genetics have facilitated the understanding of the pathogenesis of sporadic and hereditary CRC syndromes. The development of technology has enabled data collection for a number of genetic factors, which lead to understanding of the molecular mechanisms underlying CRC. The incidence and the nature of CRC is a mixture of genetic and environmental factors. The current field of interest is to understand how molecular basis could shape predisposition for developing CRC, disease progression and response to chemotherapy. In this article, we summarize new and developing genetic markers, and assess their clinical value for inherited and sporadic CRC.
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    How is nerve-sparing surgery well performed?
    (2012)
    Krivokapic, Zoran (55503352000)
    ;
    Dimitrijevic, Ivan (59595303500)
    Surgical treatment of rectal cancer is associated with a risk of autonomic nerve damage, and consequence of this may be sexual and urinary dysfunction. The improvement of our understanding of the anatomy and physiology of sexual and urinary function together with continual sophistication of surgery for rectal cancer has decreased the incidence of sexual and urinary dysfunction after rectal surgery. Despite these advances, mentioned functional deficits still present significant factor in the impaired quality of life of these patients. Awareness of the degree of risk for postoperative sexual and urinary dysfunction is important both for the patient and as a standard for appraisal of individual colorectal practice. © 2012 Springer-Verlag Berlin Heidelberg. All rights are reserved.
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    Microsatellite instability affecting the T17 repeats in intron 8 of HSP110, as well as five mononucleotide repeats in patients with colorectal carcinoma
    (2013)
    Markovic, Srdjan (57210721043)
    ;
    Antic, Jadranka (36627982000)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Zogovic, Branimir (54404258600)
    ;
    Bojic, Daniela (36928115900)
    ;
    Svorcan, Petar (8950517800)
    ;
    Markovic, Velimir (57206490091)
    ;
    Krivokapic, Zoran (55503352000)
    Aim: To investigate mononucleotide markers: BAT-25, BAT-26, NR-21, NR-22 and NR-24 in patients with colorectal cancer (CRC), and the status of HSP110T17, KRAS, BRAF and the MLH1 promoter mutations in microsatellite unstable CRC. Methods: Genetic assessments were performed on samples obtained following resection of CRC in 200 patients. Results: Allelic variations of HSP110T17 were found in all 18 patients with microsatellite instabilities (MSIs) in at least three markers (high-frequency MSI). By contrast, mutations of HSP110T17 were absent in all 20 patients with no MSI frequency. Eight out of 182 patients with low (instability in one marker) or no frequency MSI had allelic shifts due to polymorphisms of BAT-25 (1.5%), NR-21 (1.75%) and NR-24 (1.5%). BRAF mutations were associated with >5 bp shortening of HSP110T17. Conclusion: Patients with high-frequency MSI CRC had allelic variations of HSP110T17. BRAF mutations occur along with greater shortening in HSP110T17 during oncogenesis via the MSI pathway. © 2013 Future Medicine Ltd.
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    Microsatellite instability affecting the T17 repeats in intron 8 of HSP110, as well as five mononucleotide repeats in patients with colorectal carcinoma
    (2013)
    Markovic, Srdjan (57210721043)
    ;
    Antic, Jadranka (36627982000)
    ;
    Dimitrijevic, Ivan (59595303500)
    ;
    Zogovic, Branimir (54404258600)
    ;
    Bojic, Daniela (36928115900)
    ;
    Svorcan, Petar (8950517800)
    ;
    Markovic, Velimir (57206490091)
    ;
    Krivokapic, Zoran (55503352000)
    Aim: To investigate mononucleotide markers: BAT-25, BAT-26, NR-21, NR-22 and NR-24 in patients with colorectal cancer (CRC), and the status of HSP110T17, KRAS, BRAF and the MLH1 promoter mutations in microsatellite unstable CRC. Methods: Genetic assessments were performed on samples obtained following resection of CRC in 200 patients. Results: Allelic variations of HSP110T17 were found in all 18 patients with microsatellite instabilities (MSIs) in at least three markers (high-frequency MSI). By contrast, mutations of HSP110T17 were absent in all 20 patients with no MSI frequency. Eight out of 182 patients with low (instability in one marker) or no frequency MSI had allelic shifts due to polymorphisms of BAT-25 (1.5%), NR-21 (1.75%) and NR-24 (1.5%). BRAF mutations were associated with >5 bp shortening of HSP110T17. Conclusion: Patients with high-frequency MSI CRC had allelic variations of HSP110T17. BRAF mutations occur along with greater shortening in HSP110T17 during oncogenesis via the MSI pathway. © 2013 Future Medicine Ltd.

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