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Mirsad Dorić, D. Junuzović, Edina Lazović-Salčin, Suada Kuskunović-Vlahovljak, S. Radović, Nina Čamdžić, M. Babić, Haris Čampara

Introduction: The aims of this study were to investigate the immunohistochemical expression of cyclooxygenase-2 (COX- 2) and vascular endothelial growth factor-C (VEGF-C), their correlation with lymphangiogenesis, angiogenesis and clinicopathological significance in human gastric cancer. Material and methods: Tissue samples of gastric cancer of 60 patients, who underwent Billroth II resection, were analyzed. The expression of COX-2 and VEGF-C proteins was calculated using a semi-quantitative immunoreactive score method. Quantitative analysis of lymphangiogenesis and angiogenesis was performed according to the method described by Weidner. Lymphangiogenesis was evaluated by immunostaining with D2-40. Angiogenesis was assessed by CD105 immunostaining. Results: There was a statistically significant difference in the mean values of COX-2 (p< 0.01) and VEGF-C (p< 0.05) between gastric cancer samples and in control samples. Angiogenesis was significantly higher in neoplastic tissue then in control group (p<0.001). Expression of COX-2 showed a significant positive linear correlation with angiogenesis (p<0.05). However, COX-2 did not correlate with VEGF-C or lymphangiogenesis. There was an association between VEGF-C and lymphangiogenesis, but without statistical significance. Lymphangiogenesis significantly correlated with lymph node metastasis (p=0.007). Expression of COX-2 showed significant correlation with type of Bormann’s classification (p=0.019) and depth of invasion (p=0.03). Conclusions: The tumor cells are the major source of COX-2 and VEGF-C in gastric carcinomas. Their correlation did not show that COX-2 overexpression promotes tumor lymphangiogenesis through augmentation of VEGF-C. The results of this study suggest that neoangiogenesis is a dominant process during tumor progression, whereas lymphangiogenesis plays an important role in lymph node metastasis. Keywords: angiogenesis, CD105, COX-2, D2-40, gastric cancer, lymphangiogenesis, VEGF-C

H. Spahović, Ü. Göktolga, D. Junuzović, C. Göktaş, A. Rama

Introduction: Main categorisation of azospermic is in two grups: nonobstructive azoospermia (NOA) and obstructive azoospermia (OA). We had evaluation of prognostic factors and determinants in sperm retrieval procedures in azoospermic patients. Methods: Retrospective evaluation observed 21 selected patients with NOA and OA azoospermia, after that complete history, physical examination with ultarsound volume of testis and hormonal profile. Hormonal profile included: follicle stimulating hormone (FSH), luteinizing hormone (LH), testosteron (T) and prolactin (P) serum levels. Also karyotype and Y-deletion analysis were done and analyzed. Results: 9 OA patients (42,9%) were undergone for TESE operation and 12 NOA patients (57,1%) for Micro-TESE operation. All TESE procedures were positive (100%). Micro-TESE in 12 selected NOA patients, 5 patients (41,6%) were positive and 7 patients (58,4%) negative. Patients testicular size, serum FSH and testosterone level showed correlation in success of sperm retrieval procedures. Conclusion: TESE is elected procedure for obstructive azospermia (OA). Micro-TESE is appropriate sperm retrieval procedurec for patients with non-obstructive azoospermia (NOA) and correlate with high FSH and small volume of testis.

Z. Lepara, D. Junuzović, B. Kulovac, S. Sadović, J. Kovačević, Almir Fajkić, O. Lepara, E. Bašić

Objectives: The aim of this study was to evaluate serum C-reactive protein (CRP) concentration in patients with bladder cancer, as well as to determine its potential role as biomarker in the differentiation of different stages of the disease. Methods: The study included 90 patients with bladder carcinoma who were divided into 3 groups: 30 patients with non-invasive, superficial (Ta), 30 patients with superficial (T1), and 30 patients with invasive (T2-T4) bladder cancer. Serum CRP level was determined by laser nephelometry. Results: Serum CRP levels in T2-T4 group of patients was 8.65 (3.20-18.20) mg/dL and significantly higher compared to the serum CRP level in Ta group of patients (1.55 (0.67 - 3,35) mg/dL; p<0.005), T1 group (1.90 (1.27-7.20) mg/dL, p=0.006) and compared to the control group of patients (1.20 (0.90-2.10) mg/dL; p<0.005). Multiple linear regression revealed that serum CRP level was independently associated with the tumor size (β = 0.376; p<0.001). There was an independent positive association between CRP and high progressing potential of the bladder cancer. Conclusion: CRP might have a significant role as a biomarkerin the diagnosis of this disease, with special attention on its potential role in differentiating different stages of the disease. Keywords: C-reactive protein, bladder cancer, biomarker, inflammation

S. Bajramović, D. Junuzović, N. S. Bajramovic, A. Kešmer

S. Bajramović, D. Junuzović, N. S. Bajramovic

S. Bajramović, D. Junuzović

Study design, materials and methods Between 2011-2013 we have done 30 midurethral slings (TOT) for stress urinary incontinence by self tailored polypropylene mesh. Concomitant surgeries were excluded. Sucess rate was measured in terms of overall urinary incontinence, which required a negative pad test, no urinary incontinence, a negative cough and Valsava stress test, no self reported symptoms, no retreatment for the condition. We have also asseses postoperative urge incontinence, voiding dysfunction, and adverse events

D. Junuzović, J. Prstojevic, M. Hasanbegović, Z. Lepara

ABSTRACT Introduction: Elimination of stone is determined by size and its localization. Stone from the ureter in 80% of cases can be eliminated spontaneously. If the stone by its characteristics is not spontaneously eliminated, taken are further steps and therapeutic protocols to solve this problem. Material and methods: The study was prospective, open and comparative. It was conducted at the Urology Clinic Clinical Center of Sarajevo University in the period from 2007 to 2013. The study included 404 patients with urinary tract lithiasis treated by ESWL. ESWL treatment is performed on the machine Siemens Model Lithostar Multiline, which has a combined ultrasonographic and fluoroscopic display, large energy density in order to obtain optimum focus (without damaging surrounding tissue) and minimal pain that on rare occasions requires for mild sedation-sedation. Results: From a total of 404 patients included in the study there were 234 (57.92%) male and 170 (42.08%) female patients. The most common type of stone both in female and male patients was calcium type. From a total of 262 calcium stones, 105 of them (40.07%) was present in female patients and 157 (59.92%) in male. Share of infectious type of stone in female patients was 63 (49.60%) and 64 among males (50.39%). Other stones were less abundant in both the gender groups and their total number was only 17. In women their frequency was 2 (13.33%) and 13 among males (86.67%). There was a significant difference in the frequency of different types of stones by gender (x2 = 11.47, p = 0.009). Conclusion: There was no statistically significant correlation between the number of treatments and localization of stones in the ureter, as well as a statistically significant correlation between the size of the stone and the localization of calculus in the ureter.

J. Prstojevic, D. Junuzović, M. Hasanbegović, Z. Lepara, M. Selimović

Introduction: Elimination of stone is determined by size and its localization. Stone from the ureter in 80% of cases can be eliminated spontaneously. If the stone by its characteristics is not spontaneously eliminated, taken are further steps and therapeutic protocols to solve this problem. Material and methods: The study was prospective, open and comparative. It was conducted at the Urology Clinic Clinical Center of Sarajevo University in the period from 2007 to 2013. The study included 404 patients with urinary tract lithiasis treated by ESWL. ESWL treatment is performed on the machine Siemens Model Lithostar Multiline, which has a combined ultrasonographic and fluoroscopic display, large energy density in order to obtain optimum focus (without damaging surrounding tissue) and minimal pain that on rare occasions requires for mild sedation-sedation. Results: From a total of 404 patients included in the study there were 234 (57.92%) male and 170 (42.08%) female patients. The most common type of stone both in female and male patients was calcium type. From a total of 262 calcium stones, 105 of them (40.07%) was present in female patients and 157 (59.92%) in male. Share of infectious type of stone in female patients was 63 (49.60%) and 64 among males (50.39%). Other stones were less abundant in both the gender groups and their total number was only 17. In women their frequency was 2 (13.33%) and 13 among males (86.67%). There was a significant difference in the frequency of different types of stones by gender (χ2 = 11.47, p = 0.009). Conclusion: There was no statistically significant correlation between the number of treatments and localization of stones in the ureter, as well as a statistically significant correlation between the size of the stone and the localization of calculus in the ureter.

D. Junuzović, M. Hasanbegović, S. Zvizdić, S. Hamzić, Lejla Zunic

Introduction: Endoscopic surgery and endourological procedures imply the use of special instruments that are introduced into the urinary system through the urethra and percutaneous techniques that allow ante grade access to the urinary tract. The risk of urinary tract infection after endourological procedures and the use of antibiotic prophylaxis for these procedures is a question about which there is no unique opinion. Goal: The objective of this study was to determine the connection between endourological procedures and occurrence of urinary infections and to analyze the risk factors of urinary infection for patients who were hospitalized at the Urology Clinic of the Clinical Center University of Sarajevo (CCUS). Material and methods: The research was conducted as a prospective study on a sample of 208 patients of both genders, who were hospitalized at the Urology Clinic of the CCUS and to whom one of endourological procedures was indicated either for diagnostic or therapeutic purposes. All patients were clinically examined prior to endoscopic procedures and after the treatment attention was focused on the symptoms of urinary tract infections. Results: Analysis of the presence of postoperative bacteriuria shows that it has been more common in men or in 48 cases (28.1%) compared to women with 8 cases (21.6%) (p>0.05). Preoperative catheterization was statistically significantly more present in patients who have had a postoperative bacteriuria (16 or 28.6%) compared to those without bacteriuria (8 or 5.3%) (p<0.05). Analysis of the average duration of postoperative catheterization shows that patients with postoperative bacteriuria had longer duration of postoperative cauterization of 1.97±0.14 days (range 1-20 days) compared to those without postoperative bacteriuria with 1.4±0.4 days (range 0-5 days) and with a statistically significant difference (p<0.05). Antibiotic prophylaxis in relation to the occurrence of postoperative bacteriuria did not show a statistically significant difference (p> 0.05). Analysis of the correlation coefficient indicates that a statistically significant effect on the occurrence of postoperative bacteriuria have preoperative bacteriuria, duration of postoperative catheterization and duration of hospital stay, as well as the total duration of hospitalization before and after endourological treatment (p<0.05). Conclusion: It is important to emphasize that the endourological procedures are safe procedures in terms of urinary tract infections. This study should lay pathway to establishment of guidelines for the application of antibiotic prophylaxis in endourological procedures. This would standardize the perioperative use of antibiotics, taking into account the local prevalence of pathogens and antibiotic resistance, but keeping the individual approach to each patient, considering all risk factors for the development of urinary infection after endourological procedures..

D. Junuzović, M. Hasanbegović

Introduction: Endourological procedures are performed according to the principles of aseptic techniques, jet still in certain number of patients urinary tract infections may occur. Considering the risk of urinary tract infection, there is no unique opinion about the prophylactic use of antibiotics in endourological procedures. Goal: The objective of this study was to determine the connection between endourological procedures and occurrence of urinary infections and to analyze the risk factors of urinary infection for patients who were hospitalized at the Urology Clinic of the Clinical Center University of Sarajevo CCUS. Materials and Methods: The research was conducted as a prospective study on a sample of 208 patients of both genders, who were hospitalized at the Urology Clinic of the CCUS and to whom some endourological procedure was indicated for diagnostic or therapeutic purposes. We analyzed data from patient’s histories of illness, laboratory tests taken at admission and after endourological procedures, also surgical programs for endoscopic procedures. All patients were clinically examined prior to endoscopic procedures while after the treatment attention was focused to the symptoms of urinary tract infections. Results: Statistical analysis of the tested patients indicates that there is no significant difference in the presence of postoperative, compared to preoperative bacteriuria, which implies that the endourological procedures are safe procedures in terms of urinary tract infections. Preoperatively, the most commonly isolated bacteria was Escherichia coli (30.9%) and postoperatively, Enterococcus faecalis (25%). Statistically significant effect on the occurrence of postoperative bacteriuria has preoperative bacteriuria, duration of postoperative catheterization, and duration of hospitalization. Conclusion: In everyday urological practice, it is very important to identify and control risk factors for the development of urinary infection after endourological procedures, with main objective to minimize occurrence of infectious complications.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, Lejla Mehinovic, A. Mehmedović, D. Junuzović, Ivana Bjelogrlic, A. Sofić, Aleksandra Djurovic

Background: HCV infection is characterized by a tendency towards chronicity. Acute HCV infection progresses to chronic infection in 70% of cases. Hepatitis C virus infection can cause progressive liver injury and lead to fibrosis and eventually cirrhosis. The degree of histologic fibrosis is an important marker of the stage of the disease. One of current standard treatment for CHC infection is the combination of PEG-IFN α and ribavirin. Objectives: The aim of the study was to investigate the effect of the therapy with Peginterferon alfa-2a or alfa-2b plus Ribavirin on evolution of liver fibrosis in patients with chronic hepatitis C. Also, our aim was to examine whether there was a difference between the genders in the efficacy of these antiviral therapy. Our goal also was to determine effect of the therapy with Peginterferon alfa-2a or alfa-2b plus Ribavirin on evolution of liver steatosis in patients with chronic hepatitis C. Patients and Methods: A retrospective study was made of chronic hepatitis C patients who had been treated from 2005 to April 2014 at the Clinic of Gastroenterohepatology, Clinical Center University of Sarajevo. We reviewed 40 patient medical records to collect demographic, epidemiological and clinical information, as information on liver biopsies that was performed prior to the antiviral therapy and FibroScan® test that was performed after the antiviral therapy. For the processing of data SPSS (Statistical Package for the Social Sciences Program) for Windows, ver. 21.0 statistical software was used. Comparisons between qualitative and quantitative variables were performed using the Student t-test. Mann Whitney U test was used to compare differences in variables such as fibrosis stage and steatosis grade. A value of p<0.05 was considered as statistically significant. Results: After treatment, there was a statistically significant increase in the number of patients with no fibrosis (p<0.05). There was no statistically significant reduction in the number of patients with cirrhosis (F4) (p>0.05). There was significantly higher decrease of fibrosis progression at the patients that were in an mild-to-moderate fibrosis (F1/F2/F3), patients that were in advanced stage of fibrosis (F4) at the time of the pre-treatment did not have a statistically significant fibrosis reduction. We found significant association in evolution of fibrosis after treatment with PEG-IFN α2a (40) kD and PEG-IFNα2a (12,5) kD with ribavirin (p< 0.05). We also found significant association in evolution of steatosis after treatment with PEG-IFN α2a (40) kD and PEG-IFNα2a (12,5) kD with ribavirin (p < 0.05). There was statistically significant differences (p<0.05) between genders within fibrosis qualitative evolution. Conclusions: There were significant regression of fibrosis especially at the patients that were in an mild-to-moderate fibrosis (F1/F2/F3), patients that were in advanced stage of fibrosis (F4) at the time of the pre-treatment did not have a statistically significant fibrosis reduction after treatment with PEG-IFN α2a (40) kD and PEG-IFNα2b (12,5) kD with ribavirin. Our results showed significant improvement in steatosis in patients infected with HCV after treatment with PEG-IFN α2a (40) kD and PEG-IFNα2b (12,5) kD with ribavirin. Those results provides further evidence for direct involvement of HCV and antiviral therapy in the pathogenesis of hepatic steatosis. Female gender showed a higher degree of fibrosis reduction.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, Lejla Mehinovic, D. Junuzović, N. Bijedić, A. Sofić, Ivana Bjelogrlic, A. Mehmedović

Background: Various complications occur in patients with advanced stages of liver diseases. Renal dysfunction, a parameter included in the MELD score, is the most important prognostic factor. There is a strong need in clinical practice to estimate the GFR in this patients. Objectives: The aim of our study was to detect differences in renal function among patients with different stages of chronic liver diseases caused by HBV and HCV, also to determine the impact of viral etiology and gender on the values of eGFR and renal function. Patients and Methods: This was an observational cross-sectional study performed on patients with HBV and HCV chronic hepatitis, cirrhosis and HCC caused by these viruses hospitalized during period 2009–2014 in the Clinic of Gastroenterohepatology, Clinical Center University of Sarajevo. The estimated GFR (eGFR) was evaluated by the MDRD4 method. For the processing of data SPSS 21.0 statistical software was used. Statistical methods used in this study where: analysis of variance test (ANOVA test), Student’s t-test for independent samples and Pearson coefficient of correlation. The level of significance was p <0.05. Results: Among this three groups of patients there was a statistically significant difference in eGFR (F= 18.79, p<0.05), i.e. increase of degree of liver damage was related with increase of renal impairment, as reflected by a significant reduction in estimated glomerular filtration rate. Gender had no significant effect on eGFR and renal function (p>0.05), except in group of patients with HCC (p<0.05). Etiology had no significant effect on eGFR and renal (p>0.05). There was statistically significant inverse correlation between glomerular filtration rate and liver enzymes AST (-.184) and GGT (-.181). Conclusions: By calculation of GFR, we determined the existence of a significant reduction of kidney function through progression of liver damage from HBV and HCV chronic hepatitis, liver cirrhosis to HCC caused by these viruses, which drawing attention to the importance of the assessment of renal function in patients with this liver pathologies. Gender and etiology had no significant effect on eGFR and impairment of renal function. Given the statistically significant inverse correlation between eGFR and AST and GGT this liver enzymes may have important role as marker for both renal and hepatic injury.

D. Junuzović, Lejla Zunic, M. Dervisefendic, A. Skopljak, Almir Pasagić, I. Masic

Introduction: Antimicrobials are widely used in infectious diseases. Only the timely intervention will contribute to the positive outcome of the disease. Unjustified use of antimicrobial prophylaxis may have adverse effects, i.e., result in bacterial resistance to existing antimicrobials, as well as toxic effects on leukocyte lineage and other parameters of the blood. Goal: The goal of this study was to confirm that the antimicrobial therapy of urinary, gynecological and respiratory infections has a toxic effect on leukocyte lineage. Followed by lowered immunity and the emergence of risk for health complications especially in oncology and other immunodeficient patients for whom to apply pharmacotherapy it is necessary to have adequate immunity, or white blood cell count that is greater than 4.0x109/L. Material and methods: A prospective-retrospective study was conducted on a sample of 30 patients in a Primary Health Care Center in Gracanica during the period from March 01, 2013 until April 01, 2014. Testing of this sample was conducted by survey on health status and treatment, or on taking of antimicrobial therapy and other treatment regimens, with the referral diagnosis and determination of leukocytes count in by hematology counter SYSMEX. Results of leukocytes below and close to the lower reference values were statistically analyzed by Students t-test. Results: Mean WBC count in the group treated with antimicrobial therapy was 3.687±0.83 x109/L, in the group which during repeated infection did not use the antimicrobial therapy 5.09±1.04 x109/L, and in the control group of healthy subjects 7.178±1.038 x109/L. Statistical analysis with Student’s t test indicate highly significant differences between group of patients that used antimicrobial therapy with the group of patient that did not used antimicrobial during repeated infection (t=6.091; p=0.0001), as well as significant differences in mean WBC count of both of these groups and the controls (t=4.984; p=0.0001, and t=8.402, p=0.0001). Conclusion: Use of antimicrobial drugs leads to serious toxic reactions, or leukopenia. Indications for the use of antimicrobial therapy must be strictly followed, because banal, frequent infections are not indication for antimicrobial therapy. It is necessary to know the types of infection causes. Important is the proper and timely selection of antimicrobial therapy. When selecting the drug we should bear in mind its antimicrobial activity, pharmacokinetic and toxic properties, as well as patient health status. Possible is also the application of preventive medicine as well as other manner of solving infection.

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