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Z. Vukobrat-Bijedic, A. Husic-Selimovic, A. Sofić, N. Bijedić, B. Gogov, A. Djuran, Amila Redzepovic, Aida Saray et al.

Introduction: Colorectal cancer is the third most common tumor which causes high percentage of mortality in the general population. Etiologic factors which cause this disease are various, while diagnostic methods involve very complex protocols from detection of tumor markers to a combination of endoscopic and imaging methods. Goal: To determine the number of patients suffering from colon cancer for a period of two years and with endoscopic methods to verify and localize the tumor and its spread. Histopathological determination of the tumor type. Determine the concentration of CEA and CA 19-9 in the serum. Depending on the tumor location asses its progression, severity and extent by radiological imaging methods. Material and Methods: The study was prospective and retrospective, performed at the Gastroenterohepatology Clinic of the Clinical Center of Sarajevo University. During the two-year follow-up, 91 patients were hospitalized underwent endoscopy, targeted biopsy and histologically proven adenocarcinoma of the colon in which a pathologist determined grade of the cancers. Samples were eosin stained and underwent pathological histological analyzes. All patients according to tumor localization underwent CT scan and MRI of the rectum and pelvis. Results: The most common location of the cancer regardless of sex was in the recto sigmoid colon. Prevalence of colorectal cancer spread to other organs was not related to location. No significant dependence of the localization of the tumor by gender was found (p-value = 0.313). Ca 19-9 had the highest value in localization of tumors in the rectum. There was no statistically significant difference in age between men and women. The largest number of patients has adenocarcinoma grade 2 and the localization at the rectum. Conclusion: The combination of laboratory parameters (CEA and CA 19-9) with endoscopic and radiological imaging methods is essential in diagnosis of colorectal cancer and assessment of the process progression. There is a need to impose additional diagnostic parameters to detect the disease at an earlier stage.

N. Bijedić, Indira Hamulic, Z. Vukobrat-Bijedic, A. Husic-Selimovic

This research is aiming to set higher standards in healthcare research in Bosnia and Herzegovina from the aspect of mathematical and information science methodology. The data on Hepatitis C virus treatment published in previous work was reinvestigated using the Bayesian network methodology. The results are still in the line with the results published worldwide, but this research provides an additional quality, through the conditional probabilities for treatment outcome. Further development of this model may result in an acceptable prediction model for HCV treatment outcome.

A. Husic-Selimovic, S. Gornjakovic, M. Schuchmann, Z. Vukobrat-Bijedic

Budd-Chiari syndrome is a rare but life-threatening disorder characterized by obstruction of the hepatic venous outflow. Treatment depends on underlying cause, extent of the obstruction and functional capacity of the liver. When all other therapy options are unsuccessful, liver transplant should be considered. Portal vein thrombosis (PVT) is a frequent event in patients with cirrhosis which can be treated with anticoagulants, but there are limited data regarding safety and efficacy of this approach.

A. Husic-Selimovic, Z. Vukobrat-Bijedic, M. Bevanda, R. Mesihović, E. Zerem, S. Ahmetagić, S. Trbojević, A. Verhaz et al.

Association of Gastroenterologists and Hepatologists of Bosnia and Herzegovina based on the experiences of domestic and foreign centers operating in the field of hepatology and accepted guidelines of the European and the U.S. Association for Liver Diseases adopted the consensus for the diagnosis and treatment of chronic viral hepatitis B and C. The guidelines are intended for specialists in gastroenterology and hepatology, and infectious diseases physicians working in primary health care and family medicine, but also other physicians who are confronted with this disease in their practice, with the aim of facilitating and shortening the diagnostic and treatment protocols of patients with chronic viral hepatitis B and C. This ensures faster, more efficient, more rational and cost-effective care of patients with hepatitis, with an emphasis on stopping the deterioration of liver disease to liver cirrhosis and eventually hepatocellular carcinoma. Key words: Chronic hepatitis B and

INTRODUCTION Infection with hepatitis C is often manifested by a mild clinical course, and in many patients it is revealed incidentally, during routine laboratory ests. Progression of the disease often takes 10-20 years with specified high risk of fibrosis and hepatocellular carcinoma. MATERIAL AND METHODS The group of subjects with chronic liver disease of viral C etiology was consisted of 50 patients of both sexes, 38 (75%) were male and 13 (25%) females, aged 20-65 years. Patients were selected according to genotype hepatitis C viral infection and subsequently treated according to two current therapeutic protocols. All patients had prior therapy and after completion of treatment using standard methods of laboratory tests were done the following: functional hepatic tests, serological analysis, nucleic acid detection of hepatitis C virus polymerase chain reaction (PCR), quantitatively and qualitatively with the genotyping of the virus C, which determines the length of therapy. In determining the stage of chronic liver disease, histopathological examination of liver tissue samples obtained by biopsy of the liver was done and we analyzed the fibrosis and architectural changes. RESULTS By analyzing the HCV RNA PCR values at the beginning and end of treatment we tested the effect of treatment on PCR with paired samples t-test logarithm values of the PCR and came to the conclusion that the values after treatment are significantly lower with threshold of significance of 0.01. The results showed that the value of PCR before and after therapy, or achieved a response at the end of therapy, which achieved 77% of patients. The values of ALT in the group of patients with CHC were significantly higher than the values in the group of patients after the therapy. AST values in the patients with CHC were significantly higher than the values in the group of patients after therapy. There was a moderate correlation between ALT values at baseline and ALT values upon completion of treatment (0.5061). There was no correlation between HCV RNA PCR and ALT and AST. CONCLUSION Upon completion of antiviral treatment response at the end of treatment achieved 77% of patients, regardless of the genotype of the virus. Also, regardless of the genotype of the virus antiviral therapy led to statistically significant reduction of AST and ALT, indicating a direct effect of combination therapy on virological and biochemical response with no significant link between these two studied parameters.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, N. Bijedić, Aida Saray, A. Djuran, B. Gogov, Ivana Bjelogrlic

BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. The majority of GISTs are located in the stomach. Only 3-5% of GISTs are located in the duodenum associated with an increased risk of gastrointestinal bleeding as primary manifestation. AIM The aim of our study was to present frequencies of GIST in patients who underwent endoscopic procedures at Gastroenterohepatology Department due to different reasons. We also investigated the most frequent localization of GIST tumors and pathohistologicall pattern of tissue samples. PATIENTS AND METHODS Twenty two patients examined at gastroenterology department were analyzed in the period from 2005 until 2012. All of the patients were endoscopically examined ( gastroscopy, colonoscopy, endoscopic ultrasound). A few patients were referred from surgery where GIST was diagnosed during surgical procedure. Macroscopically noticed changes were pathohistologically analyzed by immunohistochemical staining (Alpha-smooth muscle actin (SMA), CD34, CD117, Ki-67 antigen, cytokeratin i desmin). RESULTS No significant difference in gender distribution of patients with GIST-s was found. We also analyzed the appearance of GIST with respect to mean patient age and no statistically significant difference was found either. However, investigation of tumor localization related to gender of patients we found a difference in gender distribution of tumor localization. In female GIST-s are more often located in the stomach than in men, with a significance level of 0.05. Immunohistochemical analysis of biopsy samples showed that CD 117 is statistically significant more frequent in men than in woman. CONCLUSION Taking in account the small sample size in our investigation over a period of seven years, we are not able to give a definitive conclusion about GIST. Further studies and observations are necessary to give a definite conclusion.

A. Husic-Selimovic, Z. Vukobrat-Bijedic, R. Mesihović, J. Huskic, N. Bijedić, S. Radović, A. Sofić

Background and Aims: Hepatic steatosis seems to be a risk factor for poor response to interferon and ribavirin therapy in patients with chronic hepatitis C. The aim of this study was to determine presence of hepatic steatosis in chronic hepatitis C and its influence on early virological response in patients treated with combined antiviral therapy (pegylated interferon and ribavirin). Methods: We studied 96 patients treated at Gastroenterohepatology Department, in the period of four years (2005-2009). There were 71 males and 25 females enrolled in this study. 72 patients had genotype 1, 5 patients had genotype 2, 17 patients had genotype 3 and 2 patients had genotype 4. Liver histology was evaluated in order to establish presence of inflammation, fibrosis and steatosis. HCV RNA levels in sera were measured by real time PCR. Early virological response (EVR) was defined as negative serum HCV RNA at week 12. In order to measure the effect influence of steatosis on early response to therapy, as well as genotype and response to therapy, we calculated relative risk and the corresponding p-value after 12 and 48 weeks. Results: The overall rate of EVR was 70%. The rate was significantly lower in the group with steatosis, regardless of the presence of micro or macrosteatosis, amounting to 60%. Serum cholesterol level was significantly higher in females than in males (7.4±0.7 vs. 5.1±0.3 mg/mL). The values of relative risks (and p-values) for effect of steatosis on the response are RRS12=8.4615 (2.87E-05), and RRS48=0.9844 (0.7399), while the values for the effect of genotype to therapy were RRG12=1.3378 (0.7543), and RRG48=3.5862 (0.2709). Conclusions: Our findings suggested that hepatic steatosis may have a strong influence on interferon therapy response in the sence that it is eight times more probable to not respond in the presence of steatosis. The presence of steatosis was highly associated with progressive disease and failure to achieve the EVR; therefore it can be a predictor of poor response to antiviral therapy.

A. Husic-Selimovic, J. Huskic, Z. Vukobrat-Bijedic, R. Mesihović, M. Gribajčević

The role of ferritin in fibrogenesis of liver parenchyma in patients with alcoholic liver disease has been investigated in previous studies. Ferritin was shown to be an indirect marker of ferum deposition in liver parenchyma in alcohol liver disease. The aim of the present study was to examine the role of nitric oxide (NO) in the pathogenesis of alcoholic liver disease as well as the influence of NO on iron (ferritin) metabolism in patients with alcoholic liver disease. Serum concentrations of NO and iron markers (iron, total iron binding capacity, ferritin) were measured in 30 male patients (aged 20-60 years) with alcoholic liver disease, as well as from a control group (30 male patients (aged 20-60 years) without liver disease). NO concentration was detected by measuring production of nitrates and nitrites using classical colorimetric Griess reactions. There was a statistically significant increase in serum NO concentration in patients with alcoholic liver disease compared to the control group (mean +/- SEM; 41,2 +/- 25,3 vs. 28,9 +/- 12,3 mmol/dm3, respectively; p<0,03). Similarly, serum iron levels (18,7 +/- 8,2 vs. 13,2 +/- 10,2 g/100 cm3, respectively; p<0,03) and serum total iron binding capacity (51,3 +/- 13,9 vs. 41,4 +/- 11,4 micromol/dm3, respectively; p<0,005) were also significantly higher in patients with alcoholic liver disease compared to control patients. The serum concentration of ferritin was 27% higher in patients with alcoholic liver disease than in the control group; however this was not statistically significant (283,2 +/- 291,0 vs. 222,9 +/- 252,0 g, respectively; p<0,4). There was no correlation between NO and ferritin in the investigated groups. These results suggest a possible role of NO and iron in the pathogenesis of alcoholic liver disease. NO and iron may be used as non-invasive predictors of liver damage. Also the role of iron in sera, and its deposition in liver parenchyma, could be used in clinical practice, especially in regards to assessing the fibrogenesis of liver parenchyma induced by ferritin.

A. Husic-Selimovic, J. Huskic, Z. Vukobrat-Bijedic, R. Mesihović, M. Gribajčević

Th e role of ferritin in fi brogenesis of liver parenchyma in patients with alcoholic liver disease has been investigated in previous studies. Ferritin was shown to be an indirect marker of ferum deposition in liver parenchyma in alcohol liver disease. Th e aim of the present study was to examine the role of nitric oxide (NO) in the pathogenesis of alcoholic liver disease as well as the infl uence of NO on iron (ferritin) metabolism in patients with alcoholic liver disease. Serum concentrations of NO and iron markers (iron, total iron binding capacity, ferritin) were measured in  male patients (aged – years) with alcoholic liver disease, as well as from a control group ( male patients (aged – years) without liver disease). NO concentration was detected by measuring production of nitrates and nitrites using classical colorimetric Griess reactions. Th ere was a statistically signifi cant increase in serum NO concentration in patients with alcoholic liver disease compared to the control group (mean ± SEM; , ± , vs. , ± , mmol/dm, respectively; p<,). Similarly, serum iron levels (, ± , vs. , ± , g/ cm, respectively; p<,) and serum total iron binding capacity (, ± , vs. , ± , μmol/dm, respectively; p<,) were also signifi cantly higher in patients with alcoholic liver disease compared to control patients. Th e serum concentration of ferritin was  higher in patients with alcoholic liver disease than in the control group; however this was not statistically signifi cant (, ± , vs. , ± , g, respectively; p<,). Th ere was no correlation between NO and ferritin in the investigated groups. Th ese results suggest a possible role of NO and iron in the pathogenesis of alcoholic liver disease. NO and iron may be used as non-invasive predictors of liver damage. Also the role of iron in sera, and its deposition in liver parenchyma, could be used in clinical practice, especially in regards to assessing the fi brogenesis of liver parenchyma induced by ferritin.

Z. Vukobrat-Bijedic, S. Radović, A. Husic-Selimovic, S. Gornjaković

The aim of the study was to verify the presence of mutated tumor suppresser gene p53 in intestinal mucosa with histologically confirmed premalignant lesions and gastric carcinoma, and assess its prognostic value. The paper presents prospective study that included 50 patients with gastric adeno-carcinoma of intestinal type that were treated at Gastroenterohepatology Clinic, and 50 patients with histologically confirmed chronic atrophic H. pylori positive gastritis. In the mucosa biopsy samples, we analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes. We typed intestinal metaplasia immunohistochemically and confirmed the presence of p53 onco-protein in antigen positive gastric carcinoma cells, and evaluated its prognostic value. Our results suggest that H. pylori acts as an initiator of inflammatory processes in gastric mucosa, which are followed by emergence of precancerous lesions. p53 is expressed late in carcinogenesis (14%) and as such, may be considered as an indicator of transformation of premalignant into malignant lesion.

S. Ladas, L. Aabakken, J. Rey, A. Nowak, S. Zakaria, K. Adamonis, N. Amrani, J. Bergman et al.

Background/Aims: Sedation rates may vary among countries, depending on patients’ and endoscopists’ preferences. The aim of this survey was to investigate the rate of using premedication for routine diagnostic upper gastrointestinal (UGI) endoscopy in endoscopy societies, members of the European Society of Gastrointestinal Endoscopy (ESGE). Methods: We evaluated a multiple-choice questionnaire which was e-mailed to representatives of national endoscopy societies, which are members of the ESGE. The questionnaire had 14 items referring to endoscopy practices in each country and the representatives’ endoscopy units. Results: The response rate was 76% (34/45). In 47% of the countries, less than 25% of patients undergo routine diagnostic UGI endoscopy with conscious sedation. In 62% of the responders’ endoscopy units, patients are not asked their preference for sedation and do not sign a consent form (59%). Common sedatives in use are midazolam (82%), diazepam (38%) or propofol (47%). Monitoring equipment is not available ‘in most of the endoscopy units’ in 46% (13/28) of the countries. Though they were available in 91% of the national representatives’ endoscopy units, they are rarely (21%) used to monitor unsedated routine diagnostic UGI endoscopy. Conclusions: In about 50% of ESGE-related countries, less than 25% of patients are sedated for routine diagnostic UGI endoscopy. Major issues to improve include availability of monitoring equipment and the use of a consent form.

Z. Vukobrat-Bijedic, S. Radović, A. Husic-Selimovic, S. Gornjaković

The aim of the study was to ascertain the existence of intestinal metaplasia in gastric mucosa of patients with gastric carcinoma coupled with H. pylori positive chronic atrophic gastritis and possible connection of IM with the development of gastric carcinoma. The paper presents prospective study that included 50 patients with gastric carcinoma and 50 patients with chronic atrophic H. pylori positive gastritis. All the patients were subjected to gastroscopy as well as biopsy targeted at antrum, lesser curvature and corpus and at the area 1-2 cm removed from tumor lesion. Biopsy samples were sliced by microtome and stained. We analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes in the mucosa and evaluated their prognostic value. We typed IM immunohistochemically. This study confirmed responsibility of H. pylori for inflammatory events in gastric mucosa in patients with gastric carcinoma. According to our findings incomplete IM of types IIa and IIb as precancerous lesion is responsible for the development of gastric carcinoma and is associated with chronic atrophic gastritis grade I and II (92% of subjects, p=0.0097, h=1, p=0.01). Thus, the finding of incomplete intestinal metaplasia may be used as an indicator for early gastric carcinoma detection. Patients with patho-histologically verified incomplete intestinal metaplasia associated with active chronic atrophic gastritis of levels I and II represent risk group for the development of gastric carcinoma of intestinal type.

Z. Vukobrat-Bijedic, S. Radović, A. Husic-Selimovic, S. Gornjaković

The aim of the study was to ascertain presence of Helicobacter pylori in gastric carcinoma as a responsible promoter of inflammatory-regenerative changes, which lead to pathological differentiation and transformation of normal epithelial cells into intestinal type and, in progression, cause epithelial dysplasia that develops into early gastric carcinoma. The paper presents prospective study that includes clinical, pathohistological and microbiological aspects of carcinogenesis initiation in gastric mucosa. The subjects are patients treated at Gastroenterohepatology Clinic divided into two groups. One group included 50 patients with gastric carcinoma while the control group included 50 patients with chronic atrophic H. pylori positive gastritis. All the patients were subjected to endoscopy as well as biopsy targeted at antrum, lesser curvature and corpus and at the region 1-2 cm removed from tumor lesion. We used HUT test to verify H. pylori presence in biopsy samples. We analyzed the samples for presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes in gastric mucosa and evaluated their meaning for the prognosis. Our study confirmed Helicobaster pylori responsibility for inflammatory events in gastric mucosa in patients with gastric carcinoma. Slight and mild epithelial dysplasia with chronic atrophic gastritis grade I and II coupled with intestinal metaplasia may be considered an indicator for early detection of carcinoma. Such patients represent risk group for gastric carcinoma development.

R. Mesihović, N. Vanis, A. Husic-Selimovic, D. Prohić, M. Gribajčević, H. Tanović, Š. Bešlić, F. Smajlović et al.

INTRODUCTION Endoscopic ultrasonography (EUS) is a well-established method of evaluating patients with gastrointestinal diseases, especially malignancies. EUS is like other similar endoscopy techniques, based on high frequency ultrasonography. This high level technology allows examination of tissue to almost microscopic level, not only in digestive system but its surrounding structures. OBJECTIVE The aim of this study was to determine the contribution of endoscopic experience, based on the number of endosopic ultrasonography examination performed in the three years period, to obtain 80% diagnostic accuracy with staging of the disease in order to achieve a 30-60% change rate in treatment decisions which is accepted standard. RESULTS First group with 210 patients was examined in the first year of work; 325 examined in the second year of work and 295 in the third year. DIAGNOSTIC Accuracy in the first year of work, were 45% (p<0.001 for the choledocholithiasis; p=0.197 for the pancreatic cancer; p=0.195 for LN detection in the gastric cancer). In the second year of work diagnostic accuracy were 78%/p=0.550 for the choledocholithiasis; p=0.228 for the pancreatic cancer; p=0.503 for LN detection in the gastric cancer/. Diagnostic accuracy in the third year of work were 81%/p<0.001 for the choledocholithiasis; p=0.018 for the pancreatic carcinoma; p=0.042 LN detection in the gastric cancer/. CONCLUSION Application of Endoscopic ultrasonography in diagnostics, based on number of EUS examination performed, after three years of work, achieved 80% diagnostic accuracy, compared to standard imaging methods and results of surgery in staging of the disease. EUS results made a change in treatment decisions in 30-60% of patients which is world standard and completely justify use of endoscopic ultrasonography in clinical practice.

N. Lacević, Z. Vukobrat-Bijedic, A. Husic-Selimovic, R. Mesihović, S. Gornjaković, D. Prohić

Recent achievements in fields of physics, microelectronical devices and informatical sciences opened huge possibilities of applications in medical specialities. Spread imaging over routine high-resolution instruments continue to be in focus of scientific researches varying from simple staining techniques to most sophisticated photodynamical techniques. Magnetic resonance imaging and computed tomography are radiological specialties, however; we mentioned them for promising achievements in computed data analysis and further improvements of virtual colonoscopy. During the last few years techniques of magnifying endoscopy have been improved including trials with narrow band endoscopy, autoflourescence endoscopy, elastic scattering spectroscopy and laser confocal microscopy. In many indications capsula endoscopy have been applied successfully.

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