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Browsing by Author "Milovanovic, Jovica (6603250148)"

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    Analysis of chromosomal aberrations frequency, haematological parameters and received doses by nuclear medicine professionals
    (2016)
    Djokovic-Davidovic, Jelena (57192953610)
    ;
    Milovanovic, Andjela (57213394852)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Antic, Vojislav (55647858000)
    ;
    Gajic, Milan (55981692200)
    Purpose: The purpose of this article was to analyse the impact of low-dose ionizing radiation to nuclear medicine professionals of the Nuclear Medicine Centre of Serbia (NMCRS). Methods: Data from the previous/initial and the last medical check-ups, obtained from the medical records of 65 employees from NMCRS, were analysed. A typical checkup, haematological parameters analysis, as well as special cytogenetical analyses, such as unstable chromosomal aberrations and micronucleus test, were carried out. For analyses of chromosomal aberrations the modified Moorhead's micro method was applied to the culture of peripheral blood lymphocytes and conventional cytogenetic technique of chromosomal aberrations was applied. The received cumulative 5-year dose was measured by personal inactive thermoluminescent dosimeters (TLD) calibrated into personal doses equivalent Hp(10). Results: An increased frequency of all unstable chromo-somal aberration forms, such as acentric chromosomes and isochromatid lesions, was noticed in the last periodical check-up as compared to the previous/initial checkups (p<0.05). As for haematological parameters, a higher erythrocytes and monocytes count in the periodical checkups was noticed (p<0.01). There was a negative correlation between reticulocytes and received 5-year cumulative dose (p<0.01). The duration of exposure had significant influence on higher level of leucocytes in the last periodical check-up (p<0.05). Conclusions: Nuclear medicine employees have increased health risks and there is a need to monitor their health condition by periodical check-ups for prevention from occupational diseases (carcinoma).
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    Analysis of chromosomal aberrations frequency, haematological parameters and received doses by nuclear medicine professionals
    (2016)
    Djokovic-Davidovic, Jelena (57192953610)
    ;
    Milovanovic, Andjela (57213394852)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Antic, Vojislav (55647858000)
    ;
    Gajic, Milan (55981692200)
    Purpose: The purpose of this article was to analyse the impact of low-dose ionizing radiation to nuclear medicine professionals of the Nuclear Medicine Centre of Serbia (NMCRS). Methods: Data from the previous/initial and the last medical check-ups, obtained from the medical records of 65 employees from NMCRS, were analysed. A typical checkup, haematological parameters analysis, as well as special cytogenetical analyses, such as unstable chromosomal aberrations and micronucleus test, were carried out. For analyses of chromosomal aberrations the modified Moorhead's micro method was applied to the culture of peripheral blood lymphocytes and conventional cytogenetic technique of chromosomal aberrations was applied. The received cumulative 5-year dose was measured by personal inactive thermoluminescent dosimeters (TLD) calibrated into personal doses equivalent Hp(10). Results: An increased frequency of all unstable chromo-somal aberration forms, such as acentric chromosomes and isochromatid lesions, was noticed in the last periodical check-up as compared to the previous/initial checkups (p<0.05). As for haematological parameters, a higher erythrocytes and monocytes count in the periodical checkups was noticed (p<0.01). There was a negative correlation between reticulocytes and received 5-year cumulative dose (p<0.01). The duration of exposure had significant influence on higher level of leucocytes in the last periodical check-up (p<0.05). Conclusions: Nuclear medicine employees have increased health risks and there is a need to monitor their health condition by periodical check-ups for prevention from occupational diseases (carcinoma).
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    Analysis of the variability of Epstein-Barr virus genes in infectious mononucleosis: Investigation of the potential correlation with biochemical parameters of hepatic involvement
    (2016)
    Banko, Ana (35774145100)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Stevanovic, Goran (15059280200)
    ;
    Cirkovic, Andja (56120460600)
    ;
    Karalic, Danijela (57403944300)
    ;
    Cupic, Maja (15730255400)
    ;
    Banko, Bojan (35809871900)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Jovanovic, Tanja (26642921700)
    Background: Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. Methods: The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. Results: The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala, as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). Conclusions: This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers. © by Ana Banko 2016.
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    Analysis of the variability of Epstein-Barr virus genes in infectious mononucleosis: Investigation of the potential correlation with biochemical parameters of hepatic involvement
    (2016)
    Banko, Ana (35774145100)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Stevanovic, Goran (15059280200)
    ;
    Cirkovic, Andja (56120460600)
    ;
    Karalic, Danijela (57403944300)
    ;
    Cupic, Maja (15730255400)
    ;
    Banko, Bojan (35809871900)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Jovanovic, Tanja (26642921700)
    Background: Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. Methods: The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. Results: The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala, as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). Conclusions: This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers. © by Ana Banko 2016.
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    Antibiofilm effects of topical corticosteroids and intranasal saline in patients with chronic rhinosinusitis with nasal polyps depend on bacterial species and their biofilm-forming capacity
    (2017)
    Cirkovic, Ivana (16309091000)
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    Pavlovic, Bojan (8212822900)
    ;
    Bozic, Dragana D. (59459661400)
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    Jotic, Ana (35173257500)
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    Bakic, Ljubica (57193098662)
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    Milovanovic, Jovica (6603250148)
    Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids and saline is a reliable option for their management. The aim of our study was to evaluate in vitro antibiofilm effects of corticosteroids and isotonic and hypertonic nasal saline in CRSwNP patients. The sinus mucosal specimens were harvested from the ethmoid cavity of 48 patients with CRSwNP and further subjected to hematoxylin–eosin staining and microbiology analysis. The biofilm-forming capacity of isolated bacterial strains was detected by microtiter-plate method and the effects of therapeutic doses of mometasone, fluticasone, isotonic and hypertonic saline on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one organism in 34 (80.9%) and two organisms in 8 (19.1%). Staphylococcus epidermidis (34%) and Staphylococcus aureus (28%) were the most prevalent bacteria in biofilms of CRSwNP patients. Corticosteroids and saline solutions significantly reduced biofilm formation (p < 0.01 and p < 0.05, respectively) with better efficacy of fluticasone and isotonic nasal saline. Treatment with fluticasone, mometasone, isotonic and hypertonic nasal saline completely prevented biofilm production in 66, 50, 84 and 38% of bacterial strains, respectively. The most significant density reduction was observed in biofilm formed by Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae compared to other bacterial species (p < 0.01, p < 0.05, p < 0.05, respectively). The antibiofilm effects of corticosteroids and saline solutions also greatly depended on bacterial biomass (p < 0.05), with the most significant effect on high compared to small amount of formed biofilm. The topical steroids and nasal saline are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and volume of formed biofilm. © 2017, Springer-Verlag Berlin Heidelberg.
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    Clinical outcome of early glottic carcinoma in Serbia
    (2013)
    Milovanovic, Jovica (6603250148)
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    Djukic, Vojko (6701658274)
    ;
    Milovanovic, Aleksandar (22035600800)
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    Jotic, Ana (35173257500)
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    Banko, Bojan (35809871900)
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    Jesic, Snezana (6603837859)
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    Babic, Borivoj (25121401500)
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    Trivic, Aleksandar (8301162500)
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    Artiko, Vera (55887737000)
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    Petrovic, Milorad (55989504900)
    ;
    Stankovic, Predrag (8301161500)
    Objective: Proposed methods for treating early glottic carcinoma are cordectomy through laryngofissure, laser cordectomy, and radiotherapy. The aim of the study was to conduct comprehensive study to evaluate oncological and functional results of different treatment modalities for Tis and T1 glottic carcinoma, identify prognostic factors for the outcome of treatment and decide where we stand in applying worldwide standards of early glottic carcinoma treatment. Methods: Prospective study was conducted on 221 patients treated with Tis and T1 glottic carcinoma from 1998 to 2003 (72 patients were treated endoscopically with CO2 laser, 75 patients with cordectomy through laryngofissure and 74 with radiotherapy), with follow-up period from 38 to 107 months. Important demographic and clinical variables were analyzed. Voice quality after the treatment was assessed using multidimensional voice analysis. Results: Comparing oncological results of three modalities of treatment, there were no significant differences. Functional results of treatment were better after laser cordectomy and primary radiotherapy than following the open cordectomy. Five-year survival rate was almost identical in all three groups of patients, and important prognostic factors for survival were age and histological grade of the tumor. Conclusion: Considering that the choice of treatment in our country is also greatly influenced by other paramedical factors, such as distance from treatment facility, reliability of follow-up, significant time delay of radiotherapy because of small number of radiology centers and strong patients' surgeon and treatment preference, we consider endoscopic laser surgery highly efficient and preferred choice of treatment for early glottic carcinoma. © 2012 Elsevier Ireland Ltd.
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    Diagnosis of mesh infection after abdominal wall hernia surgery - Role of radionuclide methods
    (2011)
    Žuvela, Marinko (6602952252)
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    Antic, Andrija (6603457520)
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    Bajec, Djordje (6507000330)
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    Radenkovic, Dejan (6603592685)
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    Petrovic, Milorad (55989504900)
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    Galun, Danijel (23496063400)
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    Palibrk, Ivan (6507415211)
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    Duric, Aleksandra (57211128674)
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    Kaznatovic, Zoran (54681975000)
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    Banko, Bojan (35809871900)
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    Milovanovic, Jovica (6603250148)
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    Milovanovic, Aleksandar (57213394853)
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    Sǎranovic, Dordije (57190117313)
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    Artiko, Vera (55887737000)
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    Sǒbic, Dragana (57202567582)
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    Obradovic, Vladimir (7003389726)
    Background/Aims: The aim of this investigation was to evaluate the role of detection of late mesh infection following incisional hernia repair with radiolabeled antigranulocyte antibodies. Methodology: Mesh infection diagnoses were set up with clinical examination and laboratory analysis and confirmed by ultrasonography (US), computerized tomography (CT), scintigraphy with 99mTc-antigranulocyte antibodies and microbiological examination. Results: Of the 17 patients investigated, 6 had a late mesh infection, and 11 had both mesh infection and recurrent incisional hernia. Clear clinical signs of late mesh infection were present in 13 patients. Four remaining patients had non-specific discomfort and recurrent incisional hernia without clinical manifestation of mesh infection ("silent infection"). US was positive in 12/17 patients, CT in 13/17 patients, while scintigraphy with antigranulocyte antibodies in 17/17 patients. Therefore, sensitivity of US was 71%, of CT 76% and of scintigraphy 100%. In four patients late mesh infection was confirmed exclusively by 99mTc-antigranulocyte antibody scintigraphy, while US and CT did not indicate the infection. Conclusions: According to the present results, scintigraphy with 99mTc antigranulocyte antibodies is a useful method for the detection of "silent" abdominal wall infections after surgery, which is very important for prompt and appropriate therapy. © H.G.E. Update Medical Publishing S.A.
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    European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Module, updated version: Preliminary psychometric data from Serbian laryngectomized patients
    (2016)
    Trivic, Sanja Krejovic (55346592200)
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    Trivic, Aleksandar (8301162500)
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    Singer, Susanne (8044967900)
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    Milovanovic, Jovica (6603250148)
    ;
    Stankovic, Predrag (8301161500)
    ;
    Mikic, Anton (22941219500)
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    Vukasinovic, Milan (23476034200)
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    Djordjevic, Vladimir (57189371857)
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    Jotic, Ana (35173257500)
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    Folic, Miljan (56497240500)
    ;
    Stevanovic, Dejan (16313807500)
    Background We provided preliminary psychometric data for the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Head and Neck Module, updated version (QLQ-H&N43) from a group of Serbian laryngectomized patients. Methods The study included 170 subjects. The QLQ-H&N43 is a 43-item questionnaire, with 12 multi-item scales and 7 single-item symptom scales. All subjects also completed the Quality of Life Questionnaire-Core 30-questions (QLQ-C30). Results Good internal consistency (Cronbach's α of above 0.7) was found for 5 of the 7 scales. All QLQ-H&N43 scales correlated negatively as predicted with all QLQ-C30 functioning scales. The correlations with the QLQ-C30 symptoms supported discriminant validity, with only one exception: the head and neck social eating scale overlapped with the QLQ-C30 pain scale. For 14 of 19 QLQ-H&N43 scale scores, significant known-group differences were observed between those who differ in type of laryngectomy, adjuvant therapy, or 5-year survival. Conclusion Preliminary evidence suggests that a great majority of the QLQ-H&N43 scales have acceptable internal consistency and promising construct validity, but more research studies are needed with other cancer groups to extend these findings. © 2015 Wiley Periodicals, Inc..
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    Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors
    (2024)
    Trivic, Aleksandar (8301162500)
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    Milovanovic, Jovica (6603250148)
    ;
    Kablar, Djurdjina (59003768900)
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    Tomic, Ana (58700815500)
    ;
    Folic, Miljan (56497240500)
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    Jotic, Ana (35173257500)
    ;
    Tomanovic, Nada (22941937200)
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    Tomic, Ana Marija (59839974000)
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    Djoric, Igor (57210624679)
    ;
    Jankovic, Marko (57218194970)
    Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings. © 2024 by the authors.
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    Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors
    (2024)
    Trivic, Aleksandar (8301162500)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Kablar, Djurdjina (59003768900)
    ;
    Tomic, Ana (58700815500)
    ;
    Folic, Miljan (56497240500)
    ;
    Jotic, Ana (35173257500)
    ;
    Tomanovic, Nada (22941937200)
    ;
    Tomic, Ana Marija (59839974000)
    ;
    Djoric, Igor (57210624679)
    ;
    Jankovic, Marko (57218194970)
    Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings. © 2024 by the authors.
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    Immune Cell and Biochemical Biomarkers in Advanced Laryngeal Cancer
    (2022)
    Jotic, Ana (35173257500)
    ;
    Milovanovic, Jovica (6603250148)
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    Savic-Vujovic, Katarina (57217857650)
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    Radin, Zorana (57208752128)
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    Medic, Branislava (56029608400)
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    Folic, Miljan (56497240500)
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    Pavlovic, Bojan (8212822900)
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    Vujovic, Aleksandar (57190496164)
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    Dundjerovic, Dusko (56515503700)
    Objective: The aim of this study was to evaluate cell and biochemical biomarkers and establish their prognostic value in patients with advanced laryngeal cancer. Material and Methods: A prospective study included 52 patients with advanced laryngeal carcinoma surgically treated at the tertiary referral center. Tumor tissue was immunohistochemically stained for T-cell markers (CD4 and CD8), and levels of cytokines (IL-6 and IL-8) and C-reactive protein were analyzed from blood samples. Results: Overall 3-year survival (OS) of patients included in the study was 69.2% and the disease specific survival (DSS) 72.5%. Higher expression of CD4+ and CD8+ were significant prognostic factors with positive impact on both OS and DSS in univariate analysis, but not in multivariate analysis. Levels of IL-8 were a significant predictor of 3-year OS and DSS survival in patients with advanced laryngeal cancer but not levels of IL-6 and CRP values. Conclusion: Though high expression of CD4 and CD8 were demonstrated in the tumor tissue, but their prognostic role was not established. Higher values of IL-8 proved to be significant negative predictor of DSS. This could further collaborate the inclusion of combination of biomarkers in assessment of favorable treatment choice in patients with advanced laryngeal carcinoma. © The Author(s) 2022.
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    Immune Cell and Biochemical Biomarkers in Advanced Laryngeal Cancer
    (2022)
    Jotic, Ana (35173257500)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Savic-Vujovic, Katarina (57217857650)
    ;
    Radin, Zorana (57208752128)
    ;
    Medic, Branislava (56029608400)
    ;
    Folic, Miljan (56497240500)
    ;
    Pavlovic, Bojan (8212822900)
    ;
    Vujovic, Aleksandar (57190496164)
    ;
    Dundjerovic, Dusko (56515503700)
    Objective: The aim of this study was to evaluate cell and biochemical biomarkers and establish their prognostic value in patients with advanced laryngeal cancer. Material and Methods: A prospective study included 52 patients with advanced laryngeal carcinoma surgically treated at the tertiary referral center. Tumor tissue was immunohistochemically stained for T-cell markers (CD4 and CD8), and levels of cytokines (IL-6 and IL-8) and C-reactive protein were analyzed from blood samples. Results: Overall 3-year survival (OS) of patients included in the study was 69.2% and the disease specific survival (DSS) 72.5%. Higher expression of CD4+ and CD8+ were significant prognostic factors with positive impact on both OS and DSS in univariate analysis, but not in multivariate analysis. Levels of IL-8 were a significant predictor of 3-year OS and DSS survival in patients with advanced laryngeal cancer but not levels of IL-6 and CRP values. Conclusion: Though high expression of CD4 and CD8 were demonstrated in the tumor tissue, but their prognostic role was not established. Higher values of IL-8 proved to be significant negative predictor of DSS. This could further collaborate the inclusion of combination of biomarkers in assessment of favorable treatment choice in patients with advanced laryngeal carcinoma. © The Author(s) 2022.
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    Morphometric analysis of Ki-67 and p16 expression in laryngeal precursor lesions
    (2013)
    Pavlovic, Bojan (8212822900)
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    Djukic, Vojko (6701658274)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Tomanovic, Nada (22941937200)
    ;
    Milovanovic, Aleksandar (57213394853)
    ;
    Trivic, Aleksandar (8301162500)
    Laryngeal precursor lesions represent areas of altered epithelium with an increased likelihood for progression to squamous cell carcinoma. The exact molecular mechanisms of malignant transformation of laryngeal mucosa are not completely clear, but are certainly due to deregulation of cell proliferation. To assess the potential value of the p16 and Ki-67 as markers of malignant progression, we undertook a retrospective immunohistochemical and morphometric analysis on biopsy specimens from patients with precancerous lesions in the larynx. Morphometric analysis of samples stained with p16 antibody showed epithelial cell positivity in 29 (100 %) of samples with simple hyperplasia, 31 (100 %) samples with basal/parabasal cell hyperplasia, 23 (88 %) samples with atypical hyperplasia and 20 (95 %) samples with in situ carcinoma. There was a significant difference in percentage of p16-positive cells between samples with simple hyperplasia and samples with in situ carcinoma. Morphometric analysis of samples stained with Ki-67 antibody showed epithelial cell positivity in 27 (93 %) of samples with simple hyperplasia, 30 (97 %) samples with basal/parabasal cell hyperplasia, 26 (100 %) samples with atypical hyperplasia and 18 (86 %) samples with in situ carcinoma. There was a significant difference not only in the percentage of Ki-67-positive cells between samples with simple hyperplasia and samples with in situ carcinoma, but also between samples with simple and basal/parabasal cell hyperplasia. Laryngeal epithelial precursor lesions show significantly opposite patterns in p16 and Ki-67 immunopositivity. Simple hyperplasia on average shows 12 % of Ki-67-positive cells and 46 % of p16-positive cells. In situ carcinoma on average shows 23 % of Ki-67-positive cells and 36 % of p16-positive cells. © Springer-Verlag Berlin Heidelberg 2013.
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    MRI in evaluation of neoplastic invasion into preepiglottic and paraglottic space
    (2014)
    Banko, Bojan (35809871900)
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    Djukic, Vojko (6701658274)
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    Milovanovic, Jovica (6603250148)
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    Kovac, Jelena (52563972900)
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    Novakovic, Zorica (54944787100)
    ;
    Maksimovic, Ruzica (55921156500)
    Objective: The purpose of this study was to evaluate whether magnetic resonance (MR) imaging can accurately predict invasion of the preepiglottic and paraglottic space in patients with laryngeal carcinoma. Identification of these fat filling spaces is important for surgical treatment and prognosis. Materials and methods: The study was based on the prospective analysis of MRI images in a series of 40 patients (90% males), overall average age 60.1 ± 7.3 years, (49-70 years), with histopathologically diagnosed laryngeal squamous cell carcinoma. Unenhanced T2w, T2w FS, T1w, and contrast-enhanced T1w FS scans were analyzed for the presence of preepiglottic and paraglottic neoplastic invasion and were compared to postoperative histopathologic analysis. Results: In 28 patients (70%) the tumor was glottic and in 12 patients (30%) supraglottic. No statistical difference was found in the number of patients with positive MRI findings in comparison to postsurgical patohistology for infiltration of the preepiglottic space (23% vs 20%, respectively). Sensitivity for infiltration of preepiglottic space was 89% and specificity was 97%. However, infiltration of the paraglottic spaces was observed more frequently on MRI than on postsurgical patohistology analysis (60% vs 40%, respectively; p< 0.05), with a sensitivity of 67% and a specificity 50%. According to MRI findings, 26 (65%) patients were classified as T3, 14 (35%) patients as T2 while according to histopathologic analysis of specimens after surgery, 19 patients were classified as T3 (48%) and 21 as T2 (52%). Conclusion: MRI has been shown to be a reliable method for assessment of preepiglottic space while the diagnostic accuracy in patients with infiltration of the paraglottic space is limited. © 2014 Elsevier Ireland Ltd.
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    Precision-scored parental report questions and HL-scaled tympanometry as informative measures of hearing in otitis media 1: Large-sample evidence on determinants and complementarity to pure-tone audiometry
    (2016)
    Milovanovic, Jovica (6603250148)
    ;
    Filipovic, Snezana A. (57212796404)
    ;
    Marchisio, Paola (7101630931)
    ;
    Haggard, Mark P. (7007159749)
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    Zhang, Mary F. (57157710500)
    ;
    Spencer, Helen (7201921823)
    Introduction: In otitis media with effusion (OME), hearing loss is a core sign/symptom and basis of concern, with absolute pure-tone threshold sensitivity (in dB HL) by air-conduction providing the default measure of hearing. However several fundamental problems limiting the value of HL measures in otitis media are insufficiently appreciated. To appraise the joint value and implications of multiple hearing measures towards more comprehensive hearing assessment in OM, we examine in two related articles the interrelations and common or diverging determinants of three measures, two of them objective: binaural HL, and ACET (the published quasi-continuous scaling of binaural tympanometry to HL). The third measure is partly subjective: parentally reported hearing difficulties (RHD-4); this is the precision-scored total of the 4 items selected for the OM8-30 general purpose questionnaire for parents in OM. Methods: The Eurotitis-2 study (Total N = 2886) internationally standardises OM8-30 and its OMQ-14 short form. The clinical and parent-response variables acquired cover many issues in diagnosis, symptomatology and impact of OM. Data acquisition was built upon routine clinic practice, enabling us also to document some properties of that practice, such as patterns of missing HL data. To address possible confounding or loss of representativeness from this, we investigated the implications of substituting tympanometry-based ACET for missing HL to give an HL/ACET hybrid. ACET is the mapping of categorical tympanometry to continuous HL. We simulated degrees of artificial missingness of HL up to 35% on the 1430 complete-data cases, using random deletion, with 1000-version bootstrapping. Correlations of this HL/ACET hybrid with pure (100%) HL then documented the degree of correlation retained under dilution of HL by an admixture of ACET; we also documented distribution shapes. For RHD-4, we then probed the determining influences on severity of score as an auditory disability measure, both background ones (from centre, age, sex, socio-economic status, length of history, diagnosis and season) and the two underlying objective hearing measures (HL, ACET). We ran these multiple regressions (GLMs), for representativeness and generality, both on 1430 complete-data cases (i.e. all 3 hearing variables present) and also on supplemented samples according to data required only for particular analyses (N increased by +56% to +68%). A further method of sample supplementation (by up to +96%) used the HL/ACET hybrid. Results: Sex made negligible difference in any analysis. The particular collaborating centre, age, season and diagnosis collectively influenced presence/absence of HL data very strongly. (Area under ROC 0.944). Socio-economic status did not influence HL presence; surprisingly, nor did RHD, ACET or length of history, after control for centre, age, diagnosis and season. Of the inter-correlations between hearing measures, only the one between ACET and RHD was influenced (slightly reduced) by the inclusion of cases without HL data. In the simulated substitutions, Pearson correlation of hybrid HL/ACET with true HL remained above 0.90 for substitution by ACET of up to 30% rate of artificially 'missing' HL. Centre differences were adequately summarised by simple absolute additive differences in mean local case severity. In the determinant models for RHD on the 1430 complete-data cases, HL and the set of background determinants collectively explained broadly similar proportions of RHD's variability, totalling 36.8% explained. On the larger maximum case samples, slightly less absolute variability was explicable than on complete-case data, but relative magnitudes of contribution from individual determinants, both background and hearing measures, remained similar. The expected mean differences in RHD between diagnoses (RAOM, OME, and combined) were found, but the patterns of background and objective measure influences determining RHD did not differ significantly between the diagnoses. Conclusions: (1) In the Eurotitis-2 database, descriptive differences in various background demographic and clinical measures between cases on whom HL data were obtained versus not, were only of material magnitude for length of history and reported hearing difficulties. Such descriptive differences are not necessarily bases of confounding, so using our framework of 6 background adjuster variables, (particular collaborating centre, age, season, diagnosis, socioeconomic status and length of history) we isolated the determinants of HL data presence. The first four listed strongly predicted HL data presence/absence so are sufficient to control analyses well for any bias or confounding by HL data presence.(2) Diagnoses as OME and combined (OME + RAOM) had higher probability of HL data being present relative to RAOM, indicating that HL acquisition is chiefly seen as confirming and quantifying hearing loss in (suspect) OME, not as ruling it out (e.g. in suspected RAOM). Given this, also using RHD and or ACET as pre-triage to efficiently target capacity and/or reduce costs and opportunity costs of acquiring HL would be rational, but there was no evidence of such precise use of initial hearing-related information to decide on HL acquisition.(3) The full six background variables explained comparable variance in Reported Hearing Difficulties (RHD) to what was explained by ACET, but not quite as much as by HL. Achieving a high percentage explained (32-37% from good models) required both classes of determinant to be entered as predictors. The pattern of background determining influences for RHD was largely stable, with or without objective measures as additional predictors, and on maximum or complete-data cases. Length of history strongly determines RHD for a given concurrent HL.(4) Accepting ACET as substitute where HL was missing in OM cases gave a sample-size enhancement of 17% in Eurotitis-2, with negligible difference in the pattern of determinants. This hybrid measure can be recommended as reasonable next-best when moderate percentages of HL data are missing.(5) The stable pattern of prediction of RHD suggests that our six background determinants provide a very promising low-cost yet comprehensive framework for determination. It hence offers pluripotent statistical adjustment against confounding, applicable to RAOM, OME and combined diagnoses in any analysis using this database. Claims that it thereby offers a sufficient framework for full European standardisation of all the scores from the OM8-30 questionnaire measures await parallel demonstrations for symptom areas other than RHD. As 25% of the variance in RHD severity can be explained by the six adjusters in our framework, none of the six variables should be omitted from acquisition and analytic use in future OM research. © 2016 Elsevier Ireland Ltd.
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    Stroboscopy in detection of laryngeal dysplasia effectiveness and limitations
    (2014)
    Djukic, Vojko (6701658274)
    ;
    Milovanovic, Jovica (6603250148)
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    Jotic, Ana D. (35173257500)
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    Vukasinovic, Milan (23476034200)
    Vocal fold pathology changes the appearance and vibratory patterns observed during stroboscopic examination, but a strict correlation between the vibratory pattern and the dysplasia type does not exist. The aims of this study were to determine the role of stroboscopy in vocal fold dysplasia assessment and to determine whether stroboscopy is the deciding factor when performing laryngomicroscopy with biopsy in suspicious lesions. This prospective controlled study involved 112 patients with laryngeal dysplasia treated over a 2-year period at a tertiary medical center. Patient data and clinical, stroboscopy, laryngomicroscopy, and histopathologic reports were reviewed. During the stroboscopy, glottic occlusion, phase symmetry, periodicity, amplitude, mucosal wave, and nonvibratory segments were followed. Laryngomicroscopy with different types of endoscopic cordectomies (types I-III) was performed as a therapeutic measure, with a 12-month follow-up period. Nonvibrating segments were present in 15.1% of the patients with mild dysplasia and in 38.5% of the patients with moderate dysplasia. In 45.5% of the patients with severe dysplasia (carcinoma in situ), nonvibrating segments were absent. The amplitude of vocal fold vibrations in patients with mild dysplasia (P = 0.03) was a significant factor indicative of recurrent disease, but none of the stroboscopic signs was significant for the disease progression. Severe dysplasia can be related to both nonvibrating and vibrating vocal fold segments. Stroboscopy cannot be used reliably for classifying laryngeal dysplasia and may indicate the need to perform laryngomicroscopy with biopsy in suspicious vocal fold lesions. The warning factors for recurrence and progression of dysplasia are treatment modality, abnormal amplitude of vibration, and nonvibrating segment. © 2014 The Voice Foundation.
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    Stroboscopy in detection of laryngeal dysplasia effectiveness and limitations
    (2014)
    Djukic, Vojko (6701658274)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Jotic, Ana D. (35173257500)
    ;
    Vukasinovic, Milan (23476034200)
    Vocal fold pathology changes the appearance and vibratory patterns observed during stroboscopic examination, but a strict correlation between the vibratory pattern and the dysplasia type does not exist. The aims of this study were to determine the role of stroboscopy in vocal fold dysplasia assessment and to determine whether stroboscopy is the deciding factor when performing laryngomicroscopy with biopsy in suspicious lesions. This prospective controlled study involved 112 patients with laryngeal dysplasia treated over a 2-year period at a tertiary medical center. Patient data and clinical, stroboscopy, laryngomicroscopy, and histopathologic reports were reviewed. During the stroboscopy, glottic occlusion, phase symmetry, periodicity, amplitude, mucosal wave, and nonvibratory segments were followed. Laryngomicroscopy with different types of endoscopic cordectomies (types I-III) was performed as a therapeutic measure, with a 12-month follow-up period. Nonvibrating segments were present in 15.1% of the patients with mild dysplasia and in 38.5% of the patients with moderate dysplasia. In 45.5% of the patients with severe dysplasia (carcinoma in situ), nonvibrating segments were absent. The amplitude of vocal fold vibrations in patients with mild dysplasia (P = 0.03) was a significant factor indicative of recurrent disease, but none of the stroboscopic signs was significant for the disease progression. Severe dysplasia can be related to both nonvibrating and vibrating vocal fold segments. Stroboscopy cannot be used reliably for classifying laryngeal dysplasia and may indicate the need to perform laryngomicroscopy with biopsy in suspicious vocal fold lesions. The warning factors for recurrence and progression of dysplasia are treatment modality, abnormal amplitude of vibration, and nonvibrating segment. © 2014 The Voice Foundation.
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    Survival outcomes in surgically treated patients with advanced laryngeal cancer in Serbia
    (2020)
    Milovanovic, Jovica (6603250148)
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    Jotic, Ana (35173257500)
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    Vidovic, Ljiljana Tesic (57016646300)
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    Djukic, Vojko (6701658274)
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    Trivic, Aleksandar (8301162500)
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    Trivic, Sanja Krejovic (55346592200)
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    Radin, Zorana (57208752128)
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    Savic-Vujovic, Katarina (57217857650)
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    Milovanovic, Andjela (57213394852)
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    Banko, Bojan (35809871900)
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    Artiko, Vera (55887737000)
    Background/Aim. Laryngeal carcinomas make 1%-3% of all head and neck malignancies.Treatment outcome and survival rates depend greatly on established stage of the disease. The purpose of this study was to examine the survival of the patients with advanced laryngeal carcinoma depending on gender, age, common risk factors (tobacco and alcohol use), primary tumor localization, histopathological tumor grade, clinical TNM (tumor, node and metastasis) stage and surgical treatment of the disease. Methods. Retrospective study included 252 patients treated surgically for advanced squamocellular carcinoma of the larynx in a threeyear period with five-year follow-up. Patients included in the study were treated primary with surgery, with postoperative radiotherapy and chemotherapy depending on the stage of the disease, intraoperative findings and tumor resection borders. Overall survival and disease-specific five-year survival of patients was calculated for demographical and clinical characteristics of the patients. Results. Overall 5-year survival of patients with operable advanced laryngeal cancer included in the study was 86.14% and disease-specific survival 86.51%. Lower overall and the disease-specific survival was associated with age, higher histological tumor grade and more extensive neck dissections. Conclusion. Primary total laryngectomy results in higher survival outcomes in cases of transglottic T3 and T4a laryngeal tumors. Patients should be informed of the likely increased mortality risks tied to the choice of surgical resection and treatment modality before their decision. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.
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    The estimation of oncological value of selective neck dissection in cervicofacial region tumors
    (2012)
    Trivic, Aleksandar (8301162500)
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    Trivic, Sanja Krejovic (55346592200)
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    Mikic, Anton (22941219500)
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    Djukic, Vojko (6701658274)
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    Milovanovic, Jovica (6603250148)
    ;
    Petrovic, Zeljko (7102549014)
    There has recently been one hundred years since George Crile demonstrated systematic cervical lymph nodes excision for treatment of patients with head and neck cancer. Due to morbidity of the radical surgical approach, the emphasis was made on surgically conservative approach, in cases where it does not have adverse effects on disease control and still offers preservation of functional and cosmetic status. Modified radical neck dissection (MRND) removes "en block" the same lymph nodes and vessels as radical dissection, but by preserving one or more non-lymphatic structures that are being entirely removed by radical dissection, it decreases postoperative morbidity. Selective neck dissections, which are being preferred by American head and neck surgeons, went even further. The research was performed at Institute for Otolaryngology and Maxillofacial Surgery of Clinical Center of Serbia in Belgrade. The study included 319 patients treated period, from January 1, 1997 to December 31, 2001, who have been followed up for at least 5 years after treatment. Having in mind that this was retrospective clinical study, i.e. longitudinal study, the choice of patients and variables was made based on patient records. Of 302 patients with determined category, the most were in T2 category (40.44%), while T1 tumors were four times less frequent. It has been observed that metastases recurrences have occurred in 57/319 (17.86%) subjects at various time intervals. By analyzing recurrent metastases according to N categories, it has been determined that the most of them were in N1 and N2 category. This was expected, as N1 category was the most represented in the entire group of patients with 137/319 (42.94%) cases, and the largest number of neck dissections - 137/291 (47.08%), primarily SND, were performed within this category. Patient five-year survival in our study has been analyzed according to N category, type of neck dissection, and recurrence of metastases (Figure 2). Over the first two years of follow-up, there has been larger survival tendency in MRND group compared to SND. The difference became comparable in the third year, and increased in favor of SND by the end of follow-up period. Although arithmetic mean value was almost the same, and median value was higher in patients with MRND, there is no significant difference in five-year survival among patients with N1 category (0.43; df=1; p>0.05).

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