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Zora Vukobrat-Bijedić

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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.

A. Sofić, Z. Vukobrat-Bijedic, A. Husic-Selimovic, N. Šehović, Deniz Buija, Dženana Eminagić, M. Banjin, A. Đuran

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.

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.

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.

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.

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.

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.

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