Evaluation of Diagnostic Efficiency of Alpha-Fetoprotein in Patients with Liver Cirrhosis and Hepatocellular Carcinoma: Single-Center Experience.

BACKGROUND: AFP serum levels are considered as diagnostic and specific for hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). AIM: This study aimed to examine the diagnostic value of AFP in the distinguishing of patients with HCC from patients with LC, and to analyse the potential correlation between AFP levels and liver disease stages. MATERIAL AND METHODS: Fifty patients with LC and fifty patients with HCC were included in this study. The majority of the patients were males, while the HBV aetiology was dominant. RESULTS: Significant differences between LC and HCC patients were detected for AST, ALT, GGT, bilirubin, AFP and AP. Patients with HCC had higher AFP values compared to LC. There was no significant correlation between the size of the tumour lesion and serum AFP levels. A positive correlation between AFP concentration and GGT activity was determined, as was the negative correlation between AFP and age of the subjects. The AFP value of 23.34 ng/m showed high sensitivity (84%) and specificity (82%). CONCLUSION: The size of the surface below the ROC curve (AUC) was 0.877 (0.80-0.95), which makes AFP a good biomarker and this diagnostic test is sufficient to separate patients with HCC and LC.

MAGNETIC RESONANCE IMAGING TO EVALUATE NEOADJUVANT THERAPY EFFECTS ON RECTAL CARCINOMA.

Although total mesorectal excision reduces the local recurrence rate in comparison to other surgical approaches, the occurrence of local relapse is still common, especially in cases when there is malignant infiltration of the circumferential resection margin. Mesorectal fascia is an important prognostic and diagnostic factor and it may be argued that mesorectal fascia represents the circumferential resection margin if total mesorectal excision is used as a surgical approach. Tumor infiltration of mesorectal fascia warrants preoperative neoadjuvant therapy in order to reduce the risk of tumor relapse. The aim of this study was to show the importance of high-resolution phased-array magnetic resonance imaging (MRI) as a modality of choice in preoperative evaluation of the effects of neoadjuvant therapy on locally advanced rectal carcinoma. This prospective comparative study included 51 patients with locally advanced rectal carcinoma that infiltrated mesorectal fascia. All study patients underwent MRI scanning twice, i.e. before and after neoadjuvant chemoradiotherapy. MRI results before and after neoadjuvant chemoradiotherapy were compared to evaluate regression of tumor length and regression of tumor infiltration of mesorectal fascia. Gender distribution of 51 patients with rectal carcinoma subjected to neoadjuvant therapy was equal, and their average age was 51 (32-81) years. MRI results showed tumor regression from mesorectal fascia following chemoradiotherapy in 36 (70.5%) cases, and Wilcoxon test showed significant differences between pretherapeutic and post-treatment MRI findings (Z=-3.162, p=0.002) in the sense of regression of tumor infiltration of mesorectal fascia. In 41 (80.3%) cases there was a reduction of tumor length, where Wilcoxon test showed differences between pretherapeutic and post-treatment MRI findings (Z=-2.754, p=0.006) in the sense of tumor length reduction. The mean pretherapeutic tumor length was 5.4 (2.3-15) cm. The mean reduction of tumor length following chemoradiotherapy was 3.56 (0.3-4.1) cm. In all 36 patients that had tumor-free mesorectal fascia following surgical treatment, the post-treatment MRI results were confirmed by histopathology. In conclusion, MRI is important for evaluation of tumor infiltration of mesorectal fascia, and is useful on patient selection for appropriate treatment for rectal carcinoma. MRI reliably evaluates the effects of neoadjuvant therapy, which contributes to better outcome of treatment for this disease.

Estimated glomerular filtration rate (eGFR) values as predictor of renal insufficiency in advanced stages of liver diseases with different etiology.

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.

Analysis of effect of antiviral therapy on regression of liver fibrosis in patient with HCV infection.

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.

Sensitivity of EUS and ERCP Endoscopic Procedures in the Detection of Pancreatic Cancer During Preoperative Staging Correlated with CT and CT Angiography Imaging Methods.

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.

Use of serum levels of proinflammatory cytokine IL-1alpha in chronic hepatitis B.

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-1alpha 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-1alpha. RESULTS AND DISCUSSION: IL-1alpha 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-1alpha 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-1alpha 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-1alpha, 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-1alpha was significantly elevated in inflammatory conditions of pronounced activity (PCR positive hepatitis). IL-1alpha 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.

Sensitivity of Symptomatology Versus Diagnostic Procedures and Concentration of CEA and CA19-9 in the Early Detection of Colorectal Cancer.

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.

Estimated Glomerular Filtration Rate (eGFR) Values as Predictor of Renal Insufficiency in Advanced Stages of Liver Diseases with Different Etiology.

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.

Impact of sustained virus elimination on natural anticoagulant activity in patients with chronic viral hepatitis C.

Previous studies have reported reduced synthesis of various hemostatic factors in patients with chronic liver disease. Whether changes in plasma levels of these proteins reflect recovered liver synthetic function following virological eradication therapy has not been approved yet. The aim of the study was to determine the impact of sustained viral suppression achieved with pegylated interferon alpha and ribavirin on hemostatic parameters including natural anticoagulants in patients with chronic hepatitis C. The following coagulation screening tests were obtained in thirty patients with chronic viral hepatitis C before and after completion of antiviral treatment: activated partial thromboplastin time, prothrombin time, plasma fibrinogen and natural anticoagulant proteins antithrombin III, protein C (PC) and total protein S (PS) activity. Only patients who achieved durable virus suppression were included. The mean PC and PS levels were significantly lower in patients with chronic viral hepatitis C before antiviral therapy than in healthy controls (79.04 ± 16.19 % vs. 109.92 ± 21.33% and 54.04 ± 16.11% vs. 87.60 ± 8.15%, respectively; (p<0.001). Mean levels of PC exhibited a significant increase by 14.69 % after the completion of antiviral treatment (93.73 ± 14.18%, p<0.001) as well as PS levels, which significantly increased by 21.46% (75.50 ± 15.43, p<0.001) when compared with pre-treatment values. No remarkable fluctuations in other hemostatic parameters were noted. Protein C and protein S are sensitive markers of hepatocyte synthetic impairment and are valuable markers in monitoring the efficacy of antiviral treatment in chronic hepatitis C patients. Larger studies are needed to confirm our results.

Intestinal amebiasis in a group of patients with ulcerative colitis: influence on clinical course of the disease.

INTRODUCTION: Ulcerative colitis (UC) is a common disease with a chronic and relapsing presentation requiring regular clinical follow up. Epidemiological and microbiologic studies suggest that enteropathogenic microorganisms play a substantial role in the clinical presentation and extent of inflammatory bowel disease. GOAL: To evaluate the presence of intestinal infections by Entamoeba hystolitica in patients with ulcerative colitis, their impact on clinical outcome, and to identify associated risk factors. MATERIAL AND METHODS: A total of 31 patients hospitalized on Gastroenterohepatology Department with patohystologically proved ulcerative colitis were studied. Fresh feces samples taken from 20 patients were examined immediately using Eosin and Lugol-staining methods and analyzing the presence of vegetative and MIFC (Meriolat and Iod staining). RESULTS: A total of 16 female and 15 male hospitalized UC patients were analysed in a period of two years (2010-2011). The mean age at diagnosis was 43 years. We analyzed relation of amoeba infection with localization of ulcerative colitis. Our results indicate that amoeba infection is related to extent of disease (they were mostly present in pancolitis). Presence of amoeba is not related to age nor gender. Furthermore, presence of amoeba was not associated with more severe clinical course of disease. Similarly, higher value of serum marker of inflammation was not associated with amoeba infection. DISCUSSION AND CONCLUSION: Amoeba infections in UC patients treated at Gastroenterohepatology Department was not related to the grade of disease activity, and other clinical variables such as gender, age and parameters of inflammation. These microorganisms could be a contributing cause of extended localization of disease.

Non-invasive liver fibrosis markers: use of serum levels of cytokines IL 1α and TGF ß1 in management of chronic liver diseases.

AIM: To analyze the usefulness of specified immunological parameters, proinflammatory IL-1α and profibrogenic, antiinflammatory TGF-ß1, along with routinely used laboratory tests, in the differential - diagnostic procedure of chronic hepatitis of infectious and noninfectious etiology. METHODS: A total of 150 subjects were divided into two groups, depending on the infectious or noninfectious etiology of liver damage, and the control group. Apart from standard laboratory tests, the analysis included serum levels of cytokines: IL-1α and TGF-ß1. RESULTS: A high degree of correlation of serum level of IL-1α with viral hepatitis has been found, especially with active replication of genetic material ( HBV-DNA or HCV-RNA-PCR positive), p less 0.01. The highest mean concentration of TGF-ß1 was noted in the group of malignant and toxic hepatitis, p less 0.0001. A negative correlation between the concentration of IL-1α and TGF-ß1 has been found (-0.18). For IL-1 α significant predictive parameters included a previous infection of hepatitis B, lower serum level of TGFß, age, use of alcohol, lower MELD and Chilld-Pugh scores. For TGF-ß1 significant predictive parameters were age, lower MELD and Child-Pugh scores, history of receiving transfusions, lower serum level of IL-1α, higher serum level of fibrinogen. A predictive model has been delivered MELD = (TGF-ß1) x 0,001- (IL-1 α) x 0,085 + CTP x 1,771-2,052; ( ± 2.04, R2=0,61; p less 0,001). CONCLUSION: Inflammatory and immune parameters, analyzed together could significantly contribute to the understanding of chronic liver damage and thus differential diagnostic procedure. IL-1α and TGF-ß1 are important parameters of inflammatory activity and fibrosis evaluation in chronic liver damage.

Cancer Antigens (CEA and CA 19-9) as Markers of Advanced Stage of Colorectal Carcinoma.

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.

Comparability of Diagnostic Methods: Proximal Endoscopy, CT and EUS in Determining Stomach Tumor Localization and their Importance in the Preoperative Analysis of Process Progression.

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.

The kinetics of virological and biochemical responses in the treatment of chronic hepatitis C by dual antiviral therapy.

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.

Diagnosis and treatment of chronic viral hepatitis B and C: doctrinary approach.

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

Correlation of pathohistotogical changes and serology parameters in chronic hepatitis C.

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.

The application of current diagnostic protocols of patients with colon cancer in preparation for therapy.

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.

Importance of sideropenic anemia in the diagnosis of gastrointestinal tract tumors.

INTRODUCTION: Sideropenic anemia is a hypochromic, microcytic anemia caused by insufficient iron level in the body. This is the most common anemia. In a large percentage it is the symptom of gastrointestinal tract cancer. Anemia was defined by hemoglobin level <119 g/dl, hematocrit <0.356 for women or hemoglobin level <138 g/dL and hematocrit <0415 for men. Gastric cancer after lung cancer is the second most common malignant tumor in the world. Frequent localization is the antrum, and less frequently in the cardia and fundus. Definite factors in the development of gastric cancer are chronic atrophic gastritis, H. pylori, intestinal metaplasia, and epithelial dysplasia as a precancerous lesion. Strong link between sideropenic anemia and gastrointestinal tract cancers recommend that patients with sideropenic anemia without a clear indication underwent same gastroscopic and colonoscopy examination. The goals were to prove sideropenic anemia, diagnose and histologically confirm tumors, tumors location and correlates anemia with tumor anemia or show the dependence of anemia on tumor. RESULTS: The study included 100 subjects (50 from counseling center for hematology that came due to sideropenic anemia and 50 patients from the Clinic for Gastroenterology who had gastrointestinal tract cancer). Respondents had regular laboratory tests and endoscopic examinations, ultrasound of the abdomen, CT of the abdomen and tumor markers. In the group of patients from Counseling center for hematology with sideropenic anemia was found 11 cancerous processes, mostly in form of gastric and colon cancer. In the group of patients hospitalized at the Clinic for Gastroenterology most cancer process were localized in the stomach and colorectum. CONCLUSION: Tumors of the gastrointestinal tract are the most common cause of sideropenic anemia, due to which the patients often first contact Counseling center for hematology. Sideropenic anemia is more common in men as also the number of digestive tract cancers in men. Sideropenic anemia has a significant place in the diagnosis of gastrointestinal tract tumors. Sideropenic anemia is most common in men after 50 years of age. The most common tumors of the gastrointestinal tube were gastric and colon cancer.

Gastrointestinal stromal tumors and its frequency in our clinical samples.

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.

[Prevention and treatment of hepatitis C infected patients on hemodialysis]. / Prevencija i lijecenje hepatitisa C kod pacijenata na hemodijalizi.

INTRODUCTION: Hepatitis C virus infection (HCV) is an important cause of morbidity and mortality in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: In this prospective, observational study, 205 patients, 37 (18%) of them with chronic HCV infection, were followed up for a one-year period at Department of Hemodialysis, Sarajevo Clinical Center, University of Sarajevo. The following parameters were analyzed: dialysis duration, sex, PCR RNA, HCV genotypes and biochemical parameters. Thirteen anti-HCV PCR RNA positive patients were treated with pegylated interferon alpha (Pegasys, Hoffman-La Roche). The goal of therapy was to reach sustained virologic response. The presence of anti-HCV antibodies in serum was detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Of 37 anti-HCV positive patients, there were 20 (54%) males and 17 (45.9%) females with the mean hemodialysis duration of 143.67 +/- 57.64 months and mean age of 54.45 +/- 8.93 years. Of 37 anti-HCV positive patients, 30 (81.08%) patients were HCV RNA PCR positive. Among HCV RNA PCR positive patients, two had up to twofold elevated ALT values, one had twofold elevated AST values, and one had sixfold elevated GGT values. Thirteen RNA PCR positive patients were treated with pegylated interferon alfa for 48 weeks. Only one patient had genotype 1 virus. Upon therapy completion, only three patients were negative by PCR RNA (genotype 1b, 23.07%) at six months and yearly follow ups remained PCR negative. CONCLUSION: Sustained virologic response was achieved in three study patients. Monitoring guidelines for infection control, isolation of seropositive patients, and strict hygienic preventive measures can prevent HCV seroconversion in hemodialysis patients.