Zora Vukobrat-Bijedic

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

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.

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.

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.

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

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.

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.

Evaluation of portal vein thrombosis in liver graft ten years after liver transplantation due to budd-Chiari syndrome using Doppler ultrasound.

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.

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.

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.

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.

Bayesian network model of HCV therapy response prediction in FBiH

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.