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Publikacije (15)

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S. Marić, S. Lukić, M. Mijailovic, L. Latinović, M. Zigic, P. Banović

Abstract 3D - Conformal Radiotherapy (3DCRT) for decades was a standard technique in the prostate cancer radical radiotherapy treatment. Technological advances and implementation of an innovative radiotherapy technique-Intensity Modulated Radiation Therapy (IMRT), enable even more precise treatment of the prostate cancer patients. Intensity Modulated Radiation Therapy (IMRT) is a technological advancement in Conformal Radiotherapy which allows superior conformity and homogeneity of the absorbed dose in planning target volume with maximal sparing organs of risk. This technique gives us possibility to escalate the radiotherapy dose, prerequisite for the adequate local tumor control. Evaluation of dosimetric parameters 3DCRT vs. IMRT: the homogeneity index, the conformity index, parameters of absorbed dose in planning target volume, dose volume constraints for organs of risk shows that IMRT is an optimal technique in the prostate cancer radical treatment.

I. Baroš, Nataša Tanasković, Ulrika Pellas, Ž. Eri, L. Latinović, T. Tot

Determination of human epidermal growth factor receptor 2 (HER2) status is important for adequate treatment of breast cancer (BC) patients. The novel HER2 gene protein assay (GPA) is particularly convenient, as it allows the simultaneous assessment of HER2 protein expression and gene amplification at individual cell level. Here we investigated the frequency of internodal HER2 heterogeneity in axillary lymph node macrometastases of BC patients and compared HER2 status between primary breast tumor and its metastases. We included a total of 41 female patients operated between 2014 and 2015 for primary BC with axillary lymph node macrometastases. Representative paraffin blocks of metastatic lymph nodes were sectioned and the slides were stained using the GPA in 38 BC cases. GPA results were assessed according to the ASCO/CAP 2013 criteria. We analyzed 12586 individual tumor cells, 120 cells per section of each metastatic lymph node. HER2 status differed between the primary tumor and its metastases in 5/38 cases (13.2%). In patients with at least two metastatic nodes, the HER2 status of lymph node metastases was only slightly different in 4/23 cases (17.4%). Our results indicate rare but substantial differences in HER2 status between primary breast tumor and its axillary lymph node metastases that may direct the choice and outcomes of targeted therapy in BC patients. The impact of the rare and subtle internodal HER2 heterogeneity evidenced in this study remains uncertain. Determining the HER2 status of lymph node metastases in BC seems to be rational, but assessing a limited number of metastatic nodes may be sufficient.

J. Ćulum, Clinic “S-tetik” Banja Luka, B. Jakovljević, D. Jović, A. Jakovljević, L. Latinović, Marinko Domuzin, Gordana Guzijan

Introduction: Until recently, gastric cancer represented the most common visceral neoplasm. In Japan, the prevalence of disease is 58.4 per 100,000 inhabitants for men and 29.9 for women. Here, the incidence is lower. Gastrectomy is the most common surgical method of treating carcinomas of the stomach. Aim of the Study: To determine which method of reconstruction after gastrectomy improves the quality of life optimally. Patients and Methods: We analyzed 221 patient operated on for gastric cancer at the Surgical Clinic of the University Clinical Center in Banja Luka, and the subject of a detailed analysis of the 111 patients who were operated with the intention of achieving curability. Results: Reflux esophagitis is dominant modality in reconstruction wth omega loop (p <0.05). Analyzing GIQLI, we found dominant modality GIQLI II in the total gastrectomy and reconstruction options RY, while predominantly GIQLI III was registered in HLR reservoir reconstruction method (p <0.01). And two hours after the ingestion of a meal labeled with a radioisotope Tc99m in artificial gastric reservoir (HLR) showed signs of radioactivity (about 10% amount). “H0 performance” (AJCC / UICC) was the most frequently recorded in subtotal gastrectomy, while there was significant appearance of “H1” and “H2” modalities with the total gastrectomy statistically. In RY reconstruction, statistically significant was participation modalities “H1”, while “H1” performance (AJCC / UICC) was the dominant modality at the HLR options reconstruction with statistically significant frequency of occurrence (p <0.01). Conclusion: The results of the assessment of quality of life are comparable with the results of other statistical series. They confirm antireflux component Roux en Y reconstructions and its intestinoplications and highlight the advantage of the nutritional components loop modifications (creation pouch-a).

N. Vasić, S. Glumac, S. Pejić, L. Amidžić, L. Latinović, B. Dožić, S. Hinic, Z. Maksimović

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a complex role in the pathogenesis of atherosclerosis. We compared (1) the histopathological findings in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD); (2) the expression of MMP-2/MMP-9 and TIMP-1/TIMP-2 in aortic layers, inflammatory cells and smooth muscle cells (SMCs), aiming to identify the common underlying pathogenic mechanisms of the disease development. Samples were obtained from 30 patients with AAA and 30 with AOD. Aortic histology and immunohistochemistry were performed to evaluate inflammatory changes and MMP and TIMP expression. Thrombosis and ulceration were more frequent in AOD than in AAA. The MMP-9 expression was elevated in all aortic layers of AAA patients and in media/adventitia of AOD patients, mainly followed by lower expression of its inhibitor TIMP-1. Higher MMP-9 expression was also found in SMCs and macrophages of both AAA and AOD specimens, while higher TIMP-1/TIMP-2 were Received May 3, 2017. Accepted February 3, 2018. The study was supported by the Ministry of Science and Technology of the Republic of Srpska. Corresponding author: Snezana Pejic, “Vinca” Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade, Serbia. Phone: (+381) 11 3408 303; Fax: (+381) 11 64 555 61; e-mail: snezana@ vin.bg.ac.rs. Abbreviations: AAA – abdominal aortic aneurysms, AOD – aortoiliac occlusive disease, ECM – extracellular matrix, HE – haematoxylin-eosin, HP – histopathological, MMPs – matrix metalloproteinases, SMCs – smooth muscle cells, TIMPs – tissue inhibitors of metalloproteinases. predominantly observed in the lymphocytes and macrophages of the aneurysm. These results showed that both conditions exhibited increased MMP-9 expression; however, the MMP expression pattern differed to some degree between the aneurysms and occlusive disease. The variations in molecular mechanisms underlying dilatative/stenosing disease warrant further investigation.

Background: To prove the frequency of thrombocytosis in patients with cancer, and the importance of anticoagulant therapy. Thrombocytosis represents an elevated platelet count of more than 350,000/mm 3 which is one of the risk factors for venous thromboembolism. Methods: This study has analyzed 146 patients who were hospitalized at the Oncology Clinic of the University Clinical Centre, Banja Luka and the Day Oncology Hospital “S.tetik”, Banja Luka in the period between 2009 and 2014. These were patients with breast tumor, gastrointestinal or gynecological malignancies. Thrombocytosis was detected in 38 patients in the moment of diagnosing. All examinees were analyzed by sex, age, primary site of tumor, presence of comorbidity, relevant laboratory analyses, clinical stage of the disease (metastatic or localized disease). Results: In the observed sample of 146 patients, thrombocytosis was detected in 38 patients in the moment of diagnosing the disease (26%). Through the follow-up, DVT (deep venous thrombosis) was found in 13 patients (34.2%) and anticoagulant therapy was administered. Out of patients who were not on anticoagulant therapy because they had no thrombotic manifestations (25 patients, 65.8%), 2 ended up experiencing the development of a clinical presentation of massive pulmonary embolism with fatal outcome. Conclusions: The occurrence of thromboembolism significantly increases morbidity and mortality, as well as the total cost of treating cancer patients. Regardless of the fact that cancer patients are at a high risk of thromboembolic events, thromboembolic prophylaxis has not been adopted as a standard therapeutic modality because of potential bleeding.

Lora Novaković Lacković, Ljiljana Tadić Latinović, Мirko Stanetić, M. Vučić, Dušan Janičić

Molecular pathology of lung adenocarcinoma, it is probably better defined as compared to other tumor types, due to its frequency, and surgical accessibility of its success in the identification of clinically important mutations in this type of cancer. EGFR (eng. Epidermal Growth Factor Receptor) mutations have been clinically most relevant mutations in lung cell carcinoma, as well as significant predictors for the therapy target chemotherapeutics. The transmembrane glycoprotein from the group of epidermal growth factor receptor is present in 10% to 15% of cases of advanced non-small cell lung cancer. The study included 29 patients in the period from Маѕ 2012 to December 2016 in the Department of Pulmonary Diseases University Clinical Centre RS implemented diagnostic and therapeutic treatment of NSCLC. All patients cytology and/or histologically confirmed adenocarcinoma of the lung, and in the Department of Pathology, University Clinical Centre RS spent additional molecular testing of existing material. The study confirms the dominance of the cited literature were adenocarcinomas and more frequent incidence in the female population and in the category of nonsmokers. The study shows that the mean duration as well as the median survival longer than one year. Kontakt osoba: Lora Novaković Lacković Original Research Respiratio

Aleksandra Salapura Dugonjić, S. Ušaj, Ž. Eri, L. Latinović

BACKGROUND/AIM In prostate tumors, angiogenesis, measured as microvessel density, is associated with tumor stage and Gleason score. The aim of this study was determine neovascularization of prostatic adenocarcinomas in core biopsies and corresponding prostatectomies. METHODS The study population included 61 patients who underwent radical prostatectomy (RP) for localized prostate carcinoma patients and did not receive chemohormonal, or radiation therapy before surgery. Tumor blocks were immunostained using the endothelial-specific antibody CD31 and subsequently evaluated at x 400 magnification in both biopsies and corresponding prostatectomies. RESULTS When comparing microvessel density in core biopsies and corresponding prostatectomies, no statistically significant difference was found (p > 0.1). A statistically significant positive correlation was found when determining correlation between microvessel density (as linear and categorical variable, i.e., with the cut-off value of 48) that was associated with the Gleason score (p < 0.05) and tumor stage (p < 0.0001). There was no correlation between microvessel density and preoperative values of serum prostate-specific antigen (PSA) (p > 0.1). CONCLUSION Microvessel density can be reliably applied to needle prostate biopsy specimens. Quantification of the microvascular density in biopsies is an accurate pre-operative predictor of tumor stage, discriminating between organ-confined and organ-extending neoplasms.

Aleksandra Salapura, S. Ušaj, Ž. Eri, L. Latinović

Introduction Increased early detection and subsequent radical surgery of prostatic cancer has prompted the search for methods and markers applicable to the initial core biopsy specimens and predictive for pathological stage and disease outcome. In prostate tumors, angiogenesis measured as microvessel density is associated with tumor stage and Gleason score. We have studied the neovascularization of prostatic adenocarcinomas in core biopsies and corresponding prostatectomies. Methods The study population included 61 patients who underwent radical prostatectomy (RP) for localized prostate carcinoma patients and did not receive chemo-, hormone, or radiation therapy before surgery. Tumor blocks  were immunostained using the endothelial - specific antibody CD31 and subsequently evaluated at x400 magnification in both biopsies and corresponding prostatectomies. Results When comparing microvessel density in core biopsies and corressponding prostatectomies, no statistical significance was found  (P˃ 0,1). Microvessel density (as linear and categorial variable, i.e. 48) was associated with Gleason score (p ˂0,05) and tumor stage (p ˂ 0,0001). There was no correlation between microvessel density and preoperative serum Prostatic specific antigen (p ˃ 0,1). Conclusions Microvessel density can be reliably applied to needle biopsy specimens. Quantification of the microvascular density in biopsies is accurate and independent pre-operative predictor of tumour stage, discriminating between organ-confined and organ-extending neoplasms.

A. Lovrenski, Milana Panjković, D. Tegeltija, L. Latinović, Jelena Krcedinac

Malignant mesothelioma is the most significant pleural tumour and it can be divided into three types: epithelial, sarcomatoid and biphasic mesothelioma. The most significant clinical manifestation of this tumour is pleural effusion. This paper was aimed at determining the role of cytological evaluation of pleural fluid in the diagnosis of malignant mesothelioma. This retrospective study included 33 medical records of patients with pleural malignant mesothelioma referred to the Institute for Lung Diseases of Vojvodina, in Sremska Kamenica in the period from 2004 to 2009. In 24 out of 33 patients, x-rays confirmed pleural effusion, thoracentesis was performed and specimens of effusion were cytologically examined at the Department of Pathology of the Institute for Lung Diseases of Vojvodina. Forty-nine cytological examinations were done. Only 2 of the first specimens were positive for malignant cells and 6 were suspicious. In repeated cytological examinations, 5 out of 6 initially suspicious specimens were positive for malignant cells, and the remaining 1 was negative. To sum up, 7 of 49 cytological examinations were positive and the sensitivity of our cytological study for the diagnosis of malignancy was 29%. Due to the low sensitivity of the cytological examinations, it has been recommended to perform biopsy of the pleura for definitive diagnosis in every patient with clinical symptoms and suspicious radiography.

N. Lučić, Z. Antonić, V. Ećim, D. Draganović, L. Latinović

INTRODUCTION Since 1897, when the first radical hysterectomy with lymphadenectomy was done by Wertheim in Vienna, this operation has had the central role in the surgical treatment of invasive cervical tumors. MATERIAL AND METHODS In the period from 1997 to 2010, 177 patients diagnosed with invasive cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) stage IB1 - II were operated at the Department of Obstetrics and Gynecology in Banja Luka. All patients underwent radical hysterectomy by Wertheim - Meigs. The aim of this study is to present the technique of this operation, as well as its effectiveness in the treatment of cervical cancer. RESULTS The distribution of the patients having invasive cervical cancer according to the International Federation of Gynecology and Obstetrics classification was as follows: I B1 - 35.67%, I B2 - 23.17%, II A - 15.48%, II B - 25.68% on average is 21.3 removed lymph glands. The rate of intraoperative and postoperative complications was 8 (4.51%) and 17 (9.60%), respectively. Of the 26 patients who were operated in the period from 2005 - 2010, 13 had stage II B according to the International Federation of Gynecology and Obstetrics; there were 6 lethal outcomes (23.08) and the five-year survival rate was 76.92%. DISCUSSION AND CONCLUSION By applying the proper surgical technique and early prevention of immediate complications, we achieved satisfactory results in operative morbity and mortality, intraoperative and postoperative complications of the lesion for radical surgery by the Wertheim-Meigs-in the treatment of cancer of the uterus in the I B - II B stage according to the International Federation of Gynecology and Obstetrics classification.

Miodrag Pavlicic, R. Gajanin, I. Klem, Ž. Eri, J. Stanić, L. Latinović

BACKGROUND: Regenerative changes may be found in bronchia, in the area of previous biopsy. Superficial epithelium in the injured area proliferates, migrates and differentiates, primarily towards the squamous cells, and then towards cup-shaped, i.e. column cells with cilia. Regenerative changes can be misinterpreted for epidermoid carcinoma. The highest level of similarity of regenerative changes and epidermoid carcinoma is between the second and the fifth day after the previous biopsy. MATERIALS AND METHODS: In this research, we used 66 biopsy samples. They were classified into two groups (33 re-biopsied between the second and the fifth day and 33 with diagnostically confirmed epidermoid carcinoma). In both groups, the same morphological parameters were monitored and then tested by means of z test with 5% tolerance (α=0.05). RESULTS: Morphological changes that are typical for epithelium in regeneration, are the following: fibrin (z=4.41; P=0.000), granulocytes (z=4.79; P=0.000), granulocytes in epithelium (z=6.92; P=0.000), infiltration into granulation tissue. Tumor changes are the following: presence of mononuclear cells (z=-3.63; P=0.0003), diskeratosis (z=-4.29; P=0.000), nuclear polymorphism (z=-4.22; P=0.000), hyperchromatism (z=-3.83; P=0.000), and infiltration into connective tissue (z=-5.76; P=0.000). Changes, which are useless for differentiation of regeneration and carcinoma, are the following: nucleoli (z=-1.77; P=0.0763), multinuclear cells (z=0.25; P=0.8041), mitoses (z=-1.44; P=0.151), interruption of the basal membrane (z=1.07; P=0.2866). CONCLUSION: Presence of squamous epithelium located in fibrin and/or granulation tissue saturated with granulocytes is a morphological characteristic of regenerative epithelium. Presence of squamous epithelium, with symptoms of severe polymorphism of nuclei, with hyperchromatism, with monocellular diskeratosis, located in cellular tissue saturated with mononuclear cells , is a characteristic of malignant epithelium.

L. Latinović, Georg Heinze, P. Birner, H. Samonigg, Hubert Hausmaninger, Ernst Kubista, W. Kwasny, Michael Gnant et al.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.

H. Bankl, P. Samorapoompichit, B. Pikula, L. Latinović, L. Latinović, H. Bankl, Klaus Lechner, Peter Valent

Recent data suggest that mast cells (MCs) and their products are involved in the pathophysiology of thrombosis. In the present study, we analyzed the number, distribution, and phenotype of prostate MCs and periprostatic MCs in patients with unilateral periprostatic vein thrombosis (PVT) by immunohistochemical analysis and electron microscopy. MCs reacted with monoclonal antibodies to tryptase, chymase, and c-kit/CD117 and stained positively for tissue-type plasminogen activator (tPA) and urokinase receptor (uPAR/CD87) but did not express detectable urokinase (uPA) or plasminogen activator inhibitors (PAI-1, PAI-2). We found an increase in the mean +/- SEM number of MCs in PVT compared with control (PVT, 14.36 +/- 1.57 vs control, 5.23 +/- 0.57/mm2). The majority of MCs accumulated in the adventitia of thrombosed veins and showed a decrease in chymase expression. As MCs increase in number in PVT and express a profibrinolytic phenotype, we hypothesize that MC-derived molecules have a role in endogenous fibrinolysis.

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