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Bisera Gogov

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The goal: The goal of this work was to give advantage to EUS as endoscopic method in diagnosis and following therapeutic treatment of pancreatic cancer in relation to radiological methods of CT and CTA. Material and Methods: The study included 49 patients, 20 women and 29 men hospitalized at the Clinic for gastroenterohepatology, due to suspicion on pancreatic cancer during observed 2 years period. All cancers were histologically and cytologically confirmed. The patients underwent ERCP as a mandatory part of staging and all patients underwent endoscopic ultrasound as well as CT or CT angiography. Results: Testing of differences was carried out using Fisher’s exact test in open-source software R. The following characteristics were tested: involvement of the blood vessels, lymph nodes, metastases, tumor size and duodenum infiltration. Results showed statistically significant difference at the 0.05 level for EUS, CT and CT angiography. Risk ratio showed that EUS is less effective in detecting infiltration of blood vessels within a malignant process then CTA where RR=0.52, CI 0.2–1.38, p-value=0.33. EUS and CTA are equal in the diagnosis of enlarged lymph nodes affected by malignancy where RR=1.3, CI 0.75–1.42, p-value=0.09. Comparison according to distant metastases showed that EUS is less effective compared to CT in approximately 30% of cases. In the diagnosis of duodenal infiltration EUS is in 5% of cases less accurate than the CT with the RR=0.95, CI 0.27–3.32, p-value=0.76, but the CTA method is more efficient because the comparison of EUS and CTA showed RR=12.52, CI 0.2–1.38, p-value=0.33. EUS as a diagnostic method is dominant in determining the size of malignant lesions located in the pancreas as compared to CT and CTA. Conclusion: EUS as endoscopic method compared to CT and CTA is one of the more invasive methods of examination but due to its ability to be performed immediately, to locate a changes smaller than 5 mm and the target biopsy option, to measure the change and that in many cases determine the relationship of malignant lesions with blood vessels, along with visualization of the surrounding lymph nodes and metastases in neighboring organs, we may give this method an advantage over other methods in the preoperative staging of patients with pancreatic cancer.

ABSTRACT Background: The reasons for the chronic viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. Interleukin-1 (IL-1) is a proinflammatory cytokine and some studies have demonstrated that IL-1 production was impaired in patients with chronic infections of hepatitis B virus, implying that IL-1 may play a role in viral clearance, progression of fibrosis and in malignant potential of HBV. In this study, along with routine laboratory tests, has been performed the analysis of serum levels of proinflammatory cytokine IL-1 α in order of better understanding and monitoring of chronic hepatitis B. Objective: The aim of this study was to analyze the usefulness of laboratory tests, which are routinely used in the assessment of liver disease with specified immunological parameters in patients with chronic hepatitis B. Patients and methods: Total of 60 subjects was divided into two groups: HBV- PCR positive and negative group. The control group of 30 healthy participants was included. Apart from standard laboratory tests, the analysis included serum levels of cytokine IL-1 α. Results and discussion: IL-1α had the highest mean concentration in group 1–viral hepatitis C, with PCR positive test (5.73 pg / ml), and then in group 2- viral hepatitis B, PCR negative test (5.39 pg / ml). ANOVA test proves that IL-1α in the healthy group (3) was different from other groups as follows: in relation to group 1 statistical significance level was p <0.001 (F = 32 75 5); in relation to group 2 was also statistically significant at p <0.001 (F = 182 361); Cytokine IL-1 was statistically analyzed separately and compared by group 1 and 2 using Student t-test for independent samples. Statistical significance was observed at p = 0.026. IL-1 α was positively correlated with the duration of the illness (p <0.01) and with serum ALT activity (p <0.01) and serum AST activity (p <0.01). Using multivariate analysis model “Factor Analysis”, was made significant stratification predictive parameters in relation to the cytokine IL-1α, stratified significance is indicated as follows: 1. Age, 2. history of receiving transfusions, 3. ALT, 4. AST, 5. MELD score (negative), 6. Child-Pugh score (Negative). Conclusion: IL-1α was significantly elevated in inflammatory conditions of pronounced activity (PCR positive hepatitis). IL-1α may have important role as marker of both inflammation and hepatic injury, particularly in the course of hepatitis B. Results suggest that inflammatory and immune parameters, analyzed together can significantly contribute to the understanding and predicting of chronic liver damage. IL-1 can be used as important parameter of inflammatory activity and fibrosis evaluation and eventually prediction of malignant transformation in chronic liver damage.

Introduction: Colorectal cancer is the major diagnostic and therapeutic problem. The number of patients in the world has increased recently. In our country it is detected late and patients visit doctor in the advanced stage of the disease with already developed metastases. Material and methods: A clinical study was conducted at the Clinic of gastroenterohepatologists, Clinical Center of Sarajevo University on 164 patients. Special attention was given to the symptoms, which are considered to be a macroscopically visible as bleeding, anemia pain, weight loss and disturbance of defecation. Smoking had no effect because a small number of observed patients smoked. Endoscopic examination revealed localization of the tumor in the colon and then underwent targeted biopsy, histological analysis by pathologist, and we determined the concentration of CEA and CA19-9 in the serum. Results: In order to get the most relevant results we used larger data set. The program used to prepare the data was Microsoft Excel 2013, and for the creation of decision trees is a used software RapidMiner version 5. Our research has shown that patients older than 55 years with significant stenosis, metastasis and diarrhea that lasted longer than 3.5 months and bleeding that lasted up to 10 months had cancer of the rectum. Bleeding that lasts longer than 10 months indicated that it was the case of cancer that was localized in the rectum in men and sigma in women. Patients older than 82.5 years and had diarrhea up to 3.5 months developed cancer in the sigma part of the colon. Analyzing pain as a symptom of an alarm, the study found that pain that lasts longer than a few days, is caused by rectal cancer, and occurs after the age of 70.5 years, and in patients younger than 63 years anemia as a alarm symptom, which lasted more than two months in men was caused by cancer of the rectum and in women cancer in other localizations within colon. In patients without stenosis developed bleeding as the most important symptom. We can say that after the age of 74 years cancer of the rectum and sigmoid is more common in men and in women dominate sigma and other locations in the colon. In patients under the 70 years of age with short time of bleeding, cancer predominates in rectum. In patients younger than 63 years can be concluded that weight loss is greater than 8 kg follows rectal cancer. In patients with bleeding that lasted one month or more as classifier occurring the age and gender. Patients younger than 74 years have rectal cancer, while older than 73 years have cancer at other sites. In women these locations are sigma and rectum. Conclusion: Based on this study we can conclude that regardless of the technical advances in medicine must pay special attention to the symptoms that doctors will refer to the localization of the tumor, stenosis of the intestine and possibly metastasis. Key words: Colorectal cancer, diagnostic procedures, concentration of CEA and CA19-9.

Introduction: Gastric cancer is one of the most common tumors in humans and is on the 14th place by frequency in the United States and it is at the 8th place by the mortality rate. In the world it takes seventh place by incidence. Today prevail the opinion and the surveys show, that it is twice as common in men as compared to women. Although there are advancements in diagnostics it must be noted that gastric cancer is still discovered late and when it already has metastasized, so that the therapeutic approach is limited and low survival rate. Patients and Methods: The study was retrospective-prospective, which covered the period from 2011 to 2012 and was performed at the Clinic of Gastroenterohepatology, Clinical Center of Sarajevo University. The study included 50 patients with gastric cancer, 34 men and 16 women. All patients underwent gastroscopy and according to tumor lesions localization divided into 3 regions: cardia, corpus and antropyloric region. Tumor lesions were biopted with histologically confirmation of gastric wall cancer. All patients underwent CT of gastric wall, CT of the abdomen and in some cases EUS was performed also. Goal: To prove by available diagnostic methods (endoscopy, CT and EUS) the presence of gastric cancer, histologically validate it and determine localization according to regions. To determine by CT the thickness of the stomach wall or the penetration of tumor lesions, the presence of enlarged lymph nodes and possible metastases. Record by EUS the progression of malignant processes in depth to layers of the wall, surrounding tissue metastases and enlarged lymph nodes. Determine the correlation between the measured parameters. Results: Our study showed that the localization of tumors at the cardia was represented in 15.31%, corpus in 17.36% and antropyloric region 16.33%. Median age he was 65.5 years with a standard deviation of 11.04. We failed to demonstrate a statistically significant difference in verified findings by EUS and age as well as endoscopic findings and age. Also there is no statistically significant difference between the CT scan and endoscopy XT = 5.99 and α = 0.05 = 0.63 XE, XE XT) and endoscopic findings and age (XT = 3.84 at α = 0.01, = 0.01 XE, XE> XT). Conclusion: Our study showed that gastric cancer are more common in men than women, metastases were more common in the elderly population, there were no significant deviations from the endoscopic findings and CT findings. EUS was performed in a small number of patients and showed as a good method because it gave accurate information about the penetration depth. Endoscopy, EUS and CT are ideal methods in diagnostic and staging of gastric cancer before the surgery.

ABSTRACT Introduction: CEA and CA 19-9 are the most common tumor associated antigens used in the staging of patients with rectal cancer and other parts of the colon. Goal: of this study was to evaluate the value of CEA and CA 19-9 in serum of patients with colon cancer and prove its place in the diagnostic staging. Material and Methods: The study was retrospective-prospective performed at the Gastroenterohepatology Clinic, Clinical Center of Sarajevo University. The study included 91 hospitalized patients who had histologically confirmed diagnosis of colon adenocarcinoma in 98% of cases. All patients underwent colonoscopy, targeted biopsy and measurement of CEA and CA 19-9 levels in serum. All of them underwent abdominal CT and MRI of the pelvis in case of rectal cancer. Results: The study analyzed 58 men and 33 women, mean age 66.6 years, with the youngest patient at age of 35 and the oldest at age of 89 years. The largest number of patients was aged 56-75 years. According to localization 77 patients had carcinoma located in the area of the rectum and sigma 37.4 and 37.4 in the rectostigmoid area and sigma. Metastases were observed in 37 patients, with predominance in the liver (22 cases) and both liver and lungs (5 cases). CEA and CA 19-9 were determined in all cases but patients with metastases had high values, especially in the two cases of cecoascendent colon cancer where detected values were extremely high (1789ng/ml and 10780U/ml). Values of CA19 -9 were significantly higher (p<0.05). CEA mean values were highest in patients aged over 75 years. In case of CA 19-9 high mean values have been recorded in patients aged over 75 years with statistically significant differences between the age groups (p<0.05). Conclusion: CEA and CA19-9 are cancer antigens that are late markers of carcinogenesis, with significantly elevated serum concentrations in case of colon cancer with already developed metastases. Older age group of patient has significantly elevated levels of both antigens. Cancer was twice more common in men than in women.

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.

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.

INTRODUCTION Viral Hepatitis C, formerly known as non A-non B hepatitis, as a separate clinical entity described in 1975 is most often reported in patients who received blood transfusions, and also called it post transfusion hepatitis. AIM OF THE STUDY Goal was to quantify the number of HCV RNA copies by PCR method, histologically determine the stage of fibrosis and degree of necroinflammatory activity in biopsies of liver parenchyma, and compare the histopathological changes with the number of the virus copies. MATERIAL AND METHODS The study was prospective and involved 50 patients suffering from chronic hepatitis C of viral etiology. All patients underwent liver biopsy and the specimens were patohistologically investigated to determine the stage of fibrosis score, and necroinflammatory activities. In every case was determined the concentration of AST, ALT, bilirubin, CBC, DR, and all underwent percutaneous ultrasonography and gastroscopy. We performed genotyping of viruses and virus quantification of HCV RNA-PCR. RESULTS The study showed that women were older than men. The stage of fibrosis and degree of necroinflammatory activities were higher in women than men, meaning that older people carry the virus longer, increasing the number of virus copies the disease lasted longer. According to the etiology of infection the patients who were infected by blood transfusions had a higher stage of fibrosis. Score of necroinflammatory activity was significantly dependent on variables AST with p = 0.02 and ALT with p = 0026. CONCLUSION Our research has shown that the stage of fibrosis was significantly dependent on alanine aminotransferases, duration of infection, number of virus copies and mode of infection. Patients who received blood transfusions, had the longest duration of infection, higher stage of fibrosis and degree necroinflammatory activity.

B. Gogov, Z. Vukobrat-Bijedic, A. Sofić, Azra Husić, S. Gornjakovic

Objectives: To assess prospects of endoscopic ultrasonography in the diagnostic methods of gastric cancer in our study and to determine the impact of this technique on the later use of therapy. Material and methods: This is a retrospective study which was conducted on the patients with histopathologic diagnosis of gastric adenocarcinoma being sent to examination with endoscopic ultrasound. We compared the initial decision concerning the therapy being based on the conventional diagnostic techniques with the application of the final therapy, which is based on the results of endoscopic ultrasound. Results: The study included 92 patients in the period from 2005 to 2010. The diagnostic precision was 71% in stage T, while in stages T1, T2, T3 and T4 the diagnostic precision was 100, 42, 78, and 100%. The sensitivity and accuracy for differentiation of T1-2 from T3- 4 was 95 and 82%. We could not identify factors associated with obtaining a correct diagnosis in staging T. The diagnostic accuracy was 74% for N stage (N0: 55% Nx 81%). The presence of the free perigastric fluid was found in 5 cases while the presence of peritoneal carcinomatosis was subsequently confirmed in 2 cases. The result of endoscopic US has led to some changes in subsequent therapeutic management in 26 patients (28%). Conclusion: Endoscopic ultrasonography is a useful technique for loco-regional staging in gastric adenocarcinoma, which can have significant implications for the therapeutic treatment of these patients.

Z. Vukobrat-Bijedic, Amina Husić-Selimović, S. Radović, S. Gornjaković, B. Gogov, Nadja Zubcević, N. Bilalović, N. Koluder

The aim of our study was to determine the genotypes of viral hepatitis C. We examined 54 patients with chronic hepatitis C who were treated at Gastroenterohepatology Department University of Sarajevo. We also monitored effects of therapeutical results in same group of patients. Polymerasa chain reaction (PCR) was used to quantified the number of HCV-RNA copies in 1 ml of blood. Genotype of virus was determined as well. We created therapeutical protocols based on genotype and quantity of virus that contained pegilated interferon alpha2a(40) kD and ribavirin. The result of our investigation presented that the highest number of patients, 25 had genotype 1a; 13 patients had genotype lb; 11 patients had genotype 3; 4 patients had genotype 4 and 1 patients with genotype 2a. At the end of therapy, 42 patients were HCV-RNA PCR negative; 7 female and 35 male. Four women with genotype 1a, responded on therapy; two with genotype 1b and one with genotype 3. Within the male group of patients (35 patients), 16 patients had a genotype 1a, 3 patients had a genotype 1b, 11 patients had a genotype 3, 4 patients had genotype 4 and one patient had genotype 2a. Patients who did not respond on therapy or were HCV-RNA-PCR positive at the end of therapy were genotype 1a and 1b. According to result of our investigation, genotype 1 is the most frequent among our patients, and the most severe damages in liver parenchyma are associated with genotype 1a and 1b. Genotype 1b also had less respond on therapy.

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