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Aim To present our experience with a diagnostic ability of endoscopic ultrasound (EUS) and magnetic retrograde cholangiopancreatography (MRCP) in cases of choledocholithiasis verified by endoscopic retrograde cholangiopancreatography (ERCP). Methods This retrospective study was conducted after a collection of data involving 58 suspected choledocholithiasis patients who underwent ERCP from January 2013 to December 2015. Patients who were diagnosed with choledocholithiasis on the basis of clinical symptoms and radiological findings and who underwent ERCP were included in this study. The first group (29 patients) underwent EUS, and the second group (29 patients) underwent MRCP. The ERCP was performed in both groups. Sensitivity, specificity and diagnostic accuracy of EUS and MRCP were determined by comparing them with ERCP, which was considered to be a gold standard. Results Gender representation was in favour of males, 58:42%. The mean age was 55.5 years. In the group 1 (EUS) 22 patients were found to have choledocholithiasis using ERCP. The EUS stone detection rate was 88%. Endoscopic ultrasound showed sensitivity (97%), specificity (67%) and accuracy (88%), positive predictive value (PPV) of 88%, negative predictive value (NPV) of 80%. In the group 2 (MRCP) 16 patients were found to have choledocholithiasis by ERCP. MRCP sensitivity was 81%, specificity 40%, PPV of 74%, NPV of 50%. Conclusion The EUS was a superior non-invasive tool in comparison with MRCP for detecting choledocholithiasis, which was confirmed using ERCP.

Aim To present our experience with a diagnostic ability of endoscopic ultrasound (EUS) and magnetic retrograde cholangiopancreatography (MRCP) in cases of choledocholithiasis verified by endoscopic retrograde cholangiopancreatography (ERCP). Methods This retrospective study was conducted after a collection of data involving 58 suspected choledocholithiasis patients who underwent ERCP from January 2013 to December 2015. Patients who were diagnosed with choledocholithiasis on the basis of clinical symptoms and radiological findings and who underwent ERCP were included in this study. The first group (29 patients) underwent EUS, and the second group (29 patients) underwent MRCP. The ERCP was performed in both groups. Sensitivity, specificity and diagnostic accuracy of EUS and MRCP were determined by comparing them with ERCP, which was considered to be a gold standard. Results Gender representation was in favour of males, 58:42%. The mean age was 55.5 years. In the group 1 (EUS) 22 patients were found to have choledocholithiasis using ERCP. The EUS stone detection rate was 88%. Endoscopic ultrasound showed sensitivity (97%), specificity (67%) and accuracy (88%), positive predictive value (PPV) of 88%, negative predictive value (NPV) of 80%. In the group 2 (MRCP) 16 patients were found to have choledocholithiasis by ERCP. MRCP sensitivity was 81%, specificity 40%, PPV of 74%, NPV of 50%. Conclusion The EUS was a superior non-invasive tool in comparison with MRCP for detecting choledocholithiasis, which was confirmed using ERCP.

There is accumulating evidence that the coagulation system is involved in the process of fibrogenesis in chronic liver disease. Recent studies postulated a possible connection between plasmatic hypercoagulability and progression of fibrosis. The aim of the study was to investigate disorders of the coagulation system in patients with chronic hepatitis C having different extent of hepatic fibrosis well defined by liver histology. A total of 62 patients with chronic hepatitis C were recruited and categorized into 2 groups according to their histological fibrosis stage : mild/moderate fibrosis group (F0-F3 group, n = 30) and extensive fibrosis/cirrhosis group (F4-F6 group, n = 32). The control group consisted of 31 healthy individuals. The following hemostatic assays were evaluated: antithrombin III (AT), protein C (PC) activity, activated partial thromboplastin time, prothrombin time, plasma fibrinogen as well as conventional liver function test. The PC level exhibited a significant reduction in both patient groups when compared to the normal control group (89.25% ± 10.05% and 48.33% ± 15.86% vs 111.86 ± 10.90; P < .001 and P < .001). The PC was found to be the strongest associated factor to histological fibrosis stage (r = –.834; P < .0001). Univariate and multivariate analysis showed that AT (P = .003) and PC (P = .0001) were the most important factors associated with advanced fibrosis. The PC (P = .001) was found to be the only predictor of mild fibrosis. In conclusion, PC deficiency occurs in an early stage of liver fibrosis. The severity of deficiency is proportional to extent of fibrosis. The PC may have a key role in linking hypercoagulability with hepatic fibrogenesis in chronic liver disease.

D. Prohić, R. Mesihović, N. Vanis, Amra Puhalović

Objective: to determine ascites and serum sodium significance in short term mortality prediction in patients with advanced liver cirrhosis. Methods: a cohort of 115 cirrhotic patients referred to our Department were followed up for 6 months in non-transplant settings. The c index equivalent to the area under the receiver operating curve (ROC) was calculated and compared to estimate the short-term prognostic accuracy of the following parameters: ascites, serum sodium and MELD score. Results: in patients with a MELD score less than 21, ascites and low serum sodium (c index 0,687, p<0 0,001 and 0,748, p<0,001 respectively) showed better prognostic accuracy and were independent predictors of mortality. For MELD scores above 21, only MELD was an independent mortality prognostic factor (c index 0,710, p<0,001). Conclusion: in our study, sample ascites and low serum sodium help identify patients with advanced liver disease who are at high risk of mortality despite low MELD scores. These parameters should be considered as additional prognostic parameters that could improve available treatment options and outcomes in this group of patients.

Immunoregulatory cytokines influence the persistence of hepatitis C virus chronic infection and the extent of liver damage. Interleukin-1 plays an important role in the inflammatory process. Some studies have demonstrated that IL-1 production was impaired in patients with chronic infections of hepatitis C virus, implying that IL-1 may play a role in viral clearance. In this study, along with routine laboratory tests, has been performed the analysis of serum levels of proinflammatory cytokine IL-1α in order of better understanding and monitoring of chronic hepatitis C. The aim of 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 C. Total of 60 subjects were divided into two groups: HCV-PCR positive and negative group. The control group of 30 healthy participans was included. Apart from standard laboratory tests, the analysis included serum levels of cytokine IL-1α. IL-1α had the highest mean concentration in group of viral hepatitis C, with PCR positive test (5.73 pg/mL), and then in of chronic viral hepatitis C, PCR negative test (5.39 pg/mL). ANOVA test proves that IL-1α in the healthy group was different from other groups as follows: in relation to HCV-RNA-PCR positive patients statistical significance level was p < 0.001 (F = 32,755); in relation to HCV-RNA-PCR negative 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-1α 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 predic- tive parameters in relation to the cytokine IL-1α, stratified significance is indicated as follows: 1. Age, 2. history of receiv- ing transfusions, 3. ALT 4. AST, 5. MELD score (negative), 6. Child-Pugh score (negative). IL-1α was significantly ele- vated 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 C. Results suggest that inflammatory and immune parameters, analyzed together can significantly contribute to the understanding and predicting of chronic liver damage.

Background: Endoscopic ultrasonography (EUS) is considered to be the most precise method for locoregional staging, was commonly used for differentiating mucosal lesions from submucosal lesions. By contrast, computed tomography (CT) was used to detect the presence of distant metastasis. Both are valuable tools for the pre-operative evaluation of gastric cancer. With the introduction of new therapeutic options and the recent improvements in CT technology, further evaluation of the diagnostic accuracy of EUS and multidetector CT (MDCT) is needed. Aim: The present study was conducted to compare the staging accuracy of EUS with that of MDCT in series of patients and to evaluate their usefulness in association with the clinicopathological factors. Patients and Methods: In total, 277 patients with gastric lesions who underwent EUS and CT, hospitalized at Department of Gastroenterology and Hepatology, Clinical Center, University of Sarajevo. The results from the pre-operative EUS and MDCT were compared with the post-operative pathological findings. Results: Among the 277 patients, the overall accuracy of EUS and MDCT for T staging was 74.7% and 76.9%, respectively. Among the 141 patients with visualized primary lesions on MDCT, the overall accuracy of EUS and MDCT for T staging was 61.7% and 63.8%, respectively. The overall accuracy for N staging was 66% and 62.8%, respectively. The performance of EUS and MDCT for large lesions and lesions at the cardia and angle had significantly lower accuracy than that of other groups. For EUS, the early gastric cancer lesions with ulcerative changes had significantly lower accuracy than those without ulcerative changes. Conclusions: For the pre-operative assessment of individual T and N staging in patients with gastric cancer, the accuracy of MDCT was close to that of EUS. Both EUS and MDCT are useful complementary modalities for the locoregional staging of gastric cancer.

D. Prohić, R. Mesihović, N. Vanis, Amra Puhalović

AIM To evaluate the easily available laboratory and clinical markers in patients with decompensated cirrhosis and compare their prognostic value. METHODS The study sample included a group of 80 patients with an established diagnosis of decompensated cirrhosis, hspitalizsed at the Department of Gastroenterohepatology, Clinical Center of the University of Sarajevo, between 2009 and 2011, followed up for 6 months either as outpatients or through repeated hspitalizsation. It was estimated that the accuracy (c-index) of the six variables, laboratory (serum bilirubin, creatinine, International Normalised Ratio (INR) and albumine) and clinical variables (hepatic encephalopathy and ascites) reflect the function of the liver in their ability to predict 6-month mortality. RESULTS Laboratory values of serum creatinine equvivalent to the area under the receiver operating characteristic curve (AUC) 0.787, 95% CI 0,667-0,898), serum bilirubin (0.701 95% CI 0,582- 0,820), INR (0.647 95% CI 0,526-0,768) and clinical parameter ascites (0.7 95%CI 0,598-0,827), showed a statistically significant prognostic accuracy in predicting six-month mortality, but none of the parameters showed excellent diagnostic accuracy . CONCLUSION Serum creatinine had the best diagnostic accuracy in predicting 6-month mortality in patients with decompensated cirrhosis and as easily available variable which could be used as predictive parameter in early prognostic assessment ofliver cirrhosis.

ABSTRACT Introduction: Gastric cancer is the fourth most common cancer and the second leading cause of death from cancer. Only complete resection of all gross disease with negative microscopic margins (R0 resection) provides a long-term survival benefit, and the overall 5-year relative survival rate is approximately 20%. To improve survival and quality of life, new therapeutic approaches have been introduced. Material and methods: A total of 277 patients (171 men, 106 women) were included in this analysis. The results from the preoperative EUS and MDCT were compared to the postoperative pathological findings. A radial scanning ultrasonic endoscope was used. In patients with early gastric cancer, especially in cases confined to mucosa, endoscopic resection is performed to avoid unnecessary surgical procedures. To achieve R0 resection for locally-advanced gastric cancer, neoadjuvant treatments have been investigated. Results and discussion: Laparoscopic surgery has been shown to improve quality of life for both early and locally advanced gastric cancer. Endoscopic ultrasonography (EUS), which is considered to be the most precise method for locoregional staging, was commonly used for differentiating mucosal lesions from submucosal lesions. By contrast, computed tomography (CT) was used to detect the presence of distant metastasis. The difference in accuracy between the ≤20-mm group and other groups was statistically significant for both EUS and MDCT (P = 0.026 and P = 0.044, respectively). Conclusion: However, recent technological advances with the helical and multi-detector scanners have provided better CT performance.

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.

N. Vanis, R. Mesihović, Lejla Ibricević, R. Dobrila-Dintinjana

The aim of the paper is to investigate significance of the endoscopic ultrasound (EUS) in diagnostic and staging of gastric lymphoma. Retrospective clinical study was conducted at the Clinic for Hematology and Clinic for Gastroenterology of the University Clinical Center of Sarajevo in the period of years 2002 to 2009. Patients (N = 40) with diagnosis of gastric lymphoma confirmed by pathohistological diagnosis were included in the study. Stage of the disease was determined based on EUS, proximal endoscopy, CT and ultrasound of abdomen, and classified according to the Ann Arbor classification. 39 patients had various types of non Hodgkin lymphoma and one patient had Hodgkin lymphoma. Based on morphological characteristics of gastric tumor visualized with EUS in 16 patients a gastric cancer was suspected. In 40% patients EUS finding was not confirmed by pathohistological finding. Compared both to CT and ultrasound of abdomen, EUS showed statistically significant higher frequency of establishing existence of infiltration (p < 0.001). In patients with primary gastric lymphoma EUS has more significant role in determination of stage of disease spread than for the diagnosis itself. Therefore EUS should be included into algorithm of patient diagnostic protocol when suspected to the malignant gastric disease.

AIM To analyze the usefulness of specified immunological parameters, proinflammatory IL-1α and profibrogenic, antiinflammatory TGF-β1, 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-β1. 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-β1 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-β1 has been found (-0.18). For IL-1 α significant predictive parameters included a previous infection of hepatitis B, lower serum level of TGFβ, age, use of alcohol, lower MELD and Chilld-Pugh scores. For TGF-β1 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-β1) 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-β1 are important parameters of inflammatory activity and fibrosis evaluation in chronic liver damage.

BACKGROUND Anaemia has been recognised as a key symptom of IBD. Although efficient therapeutic options have been developed for the treatment of IBD associated anaemia, treating anaemia often has a low priority for gastroenterologists. Compared with other manifestations of the disease, such as arthritis or osteopathy, anaemia in IBD has been given scant attention. AIM To evaluate prevalence of anaemia in patients treated for IBD in the Department of Gastroenterology and Hepatology, Clinical Centre, University of Sarajevo. PATIENTS AND METHODS The study was conducted between January 2010 and November 2012 as a retrospective observational clinical trial. Total of 210 patients were recruited. All patients with histopatological verification of IBD were divided into three groups, according to CDAI (Chronic Disease Activity Index): Biochemical parameters were recorded: full blood count, haemoglobin, haematocrit, RBC, WBC, proteinogram, fibrinogen, CRP. RESULTS Most of patients had haemoglobin serum level in range 100-120 g/l. Lower haemoglobin serum levels were measured in 40% of pts (CDAI>220). Lower haematocrit levels were detected in 38% of subjects with verified IBD ( CDAI>220). In the comparison of haematocrit level in the group of patients with CDAI>220 (moderate activity: 220-450 and high activity: >450) and CDAI<220 (low activity: 150-220) the statistical difference was at level p<0.04. In the comparison of haemoglobin level in the group of patients with moderate or high activity and low activity, by Student t-test the statistical difference was at level p<0.03. Hypoalbuminaemia was detected in 37.6% of patients. A significantly lower albumin level was in the group of moderate and high activity of IBD, at p<0.05 (ANOVA). Increased parameters of inflammation (CRP, fibrinogen and SE) were present in 35% of cases. CONCLUSION Anaemia could be the most common systemic complication of acute IBD. In our study 40 % of patients with IBD had anaemia; increased parameters of inflammation were present in 35% of cases. The control of inflammation is a key point, but often is not enough to treat anaemia. Patients should be followed up after completing treatment, and anaemia and iron deficiency actively assessed in the standard investigations.

Aims: Since its description in 1980, percutaneous endoscopic gastrostomy has become the modality of choice for providing enteral access to patients who require long-term enteral nutrition. This study aimed to evaluate current indications and complications associated with PEG feeding. Methods: We conducted a retrospective analysis of all patients who referred to our endoscopic unit of the Department of Gastroenterology and Hepatology of the Medical Center University of Sarajevo for PEG tube placement over a period of 7 years. Medical records of 359 patients dealing with PEG tube placement were reviewed to assess indications, technical success, complications and the need for repeat procedures. Results: The indications for enteral feeding tube placement were malignancy in 44% (n=158), of which 61% (n=97) patients were suffering of head and neck cancer and 39% (n=61) of other malignancy. Central nervous disease was the indication in 48.7 % (n=175) of patients. Cerebrovascular accidents (CVA) accounted for 20% (n=73), head injury for 16% (n=59) and cerebral palsy for 11% (n=38). In 6.13% (n=22) of patients minor complications occur which included wound infection (0.8%), inadvertent PEG removal (2.5%) and tube blockage (1.1%). 11 patients experienced major complications including hemorrhage, tube migration and perforation. There were no deaths related to PEG procedure placement and the overall 30-day mortality rate due to primary disease was 15.8%. Oral feeding was resumed in 23% of the patients and the tube was removed subsequently after 6 -12 months. Conclusions: Percutaneous endoscopic gastrostomy is a save and minimally invasive endoscopic procedure associated with a low morbidity (9.2%) rate, easy to follow-up and to replace when blockage occurs. Over a seven-year period we noticed an increase of 63% in PEG placement at our department.

Aida Saray, R. Mesihović, S. Gornjakovic, N. Vanis, A. Mehmedović, Kenan Nahodovic, Sanjin Glavaš, V. Papović

OBJECTIVE The aim of the study was to investigate plasma D-dimer concentration in patients with liver cirrhosis with and without ascites and to evaluate the impact of ascites depletion on circulating plasma D-dimer levels. METHODS Sixty patients with liver cirrhosis were recruited and categorized into two groups: cirrhotic patients without ascites in group 1 (n = 30) and patients with liver cirrhosis and ascites in group 2 (n = 30). D-dimer levels were measured on day of admission, in patients with ascites D-dimer concentration levels were repeated measured after ascites resolution cofirmed by ultrasonography. RESULTS Mean D-dimer levels showed significant increase in cirrhotic patients decompensated by ascites (626.0 +/- 231.08 microg/L) when compared with healthy controls (140.73 +/- 49.16 microg/L, p < 0.001). There was also a statistically significant increase of mean D-dimer levels in patients with liver cirrhosis and no evidence of ascites (333.4 +/- 109.05 microg/L, p < 0.001). In all patients after ascites resolution D-dimer levels showed significant reduction (437.66 +/- 130.47 microg/L, p < 0.05). Values of D-dimer levels achieved after abdominal paracenthesis (n = 21) where still higher than those in patients without ascites (480.14 +/- 122.85 microg/L, p = 0.001). In cirrhotic patients treated with diuretic therapy (n = 9) circulating D-dimer levels were not significantly different from those in cirrhotic patients without ascites (338.56 +/- 90.55 microg/L, p = 0.96). CONCLUSION The presence of ascites in patients with liver cirrhosis is associated with increased plasmatic fibrinolytic activity. Less aggressive ascites resolution therapy has an greater impact on reducing plasmatic fibrinolytic activity than achieved by abdominal paracenthesis.

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