Browsing by Author "Alempijevic, Tamara (15126707900)"

Background: Clinical expression of pancreas divisum is often explained as a consequence of relative or true stenosis of the minor papilla with dorsal duct obstruction. This anatomo-functional study of the minor papilla in pancreas divisum has included its topographical, functional and structural features. Materials and methods: The study was carried out on 37 human autopsy specimens of duodenopancreas, which underwent pancreatography, manometrically controlled perfusion and light microscopy. Results: One pancreas divisum was detected in the study group. In this case, the distances between the minor and the major papilla was 24.0 mm, and between the minor papilla and the superior duodenal flexure 27.4 mm. The minor papilla was patent when perfused under pressure of 10 mmHg, and its light microscopy revealed regular global histological organization with only light fibrosis and no cellular atypia. Conclusions: The structure and position of the minor papilla in pancreas divisum did not significantly differ from the ones in fused pancreases. © Springer-Verlag 2006.

The purpose of this study was to determine the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and to investigate its role as a potential risk factor in patients with chronic pancreatitis and pancreatic cancer. Deletion polymorphism of the 287-bp fragment of intron 16 of the ACE gene results in higher levels of circulating enzyme and therefore may represent a risk factor for disease development. The study included 55 patients with chronic pancreatitis, 45 patients with pancreatic cancer and 128 healthy subjects. The presence of I and D variants in the ACE gene was analyzed by a polymerase chain reaction (PCR) method. Distribution of ACE ID genotypes was analyzed by means of logistic regression. When chronic pancreatitis and pancreatic cancer groups were compared in the univariate analysis, the following factors were identified as statistically significant predictors of pancreatic disease: age, gender, smoking, fat intake, ACE II genotype and ACE DD genotype. However, in the multivariate analysis, only age, gender and smoking were singled out as predictors for the occurrence of pancreatic disease. Our findings indicate that the ACE I/D polymorphism could play a role in the development of chronic pancreatitis and pancreatic cancer through interaction with other genetic and environmental factors. © 2011 S. Karger AG, Basel.

Background: Primary biliary cirrhosis (PBC) is a chronic, progressive liver disease with elevated serum lipids. It remains unclear if hyperlipidemia increases the risk for atherosclerosis in PBC patients. Metabolic syndrome (MS) promotes the development of atherosclerotic cardiovascular disease due to abdominal obesity and insulin resistance. Aims: The aim of this study was to assess incidence and parameters of MS, as well as subcutaneous and visceral fat using noninvasive ultrasonographic measurement in patients with PBC in our population. Methods: We included 55 patients with PBC and 44 age- and sex-matched healthy controls (CG-control group). Anthropometric measurements (weight, height, and waist circumference), age, sex, and body mass index were recorded for patients and controls. Laboratory tests for assessing MS and liver function tests were analyzed. We used ultrasonography to determine subcutaneous and visceral fat diameter and area (SF, VF and SA, VA, respectively), as well as perirenal fat diameter (PF). Results: Patients with PBC had significantly higher levels of cholesterol and liver function tests. There were no statistically significant difference in serum insulin and HOMA levels, as well as incidence of MS was diagnosed in 30.9 % (17/55) PBC patients and 43.2 % (19/44) controls. We registered lower amount of VF (PBC:10.92 ± 3.63 mm, CG:16.84 ± 5.51 mm, p < 0.001), VA (PBC:403.64 ± 166.97 mm 2, CG:720.57 ± 272.50 mm 2, p < 0.001), and PF (PBC:7.03 ± 1.82 mm, CG 10.49 ± 2.70 mm, p < 0.001) in patients with PBC. Conclusion: MS is not more frequent in patients with PBC compared with healthy volunteers in our population. Lower amount of VF could be related to lower risk for cardiovascular events in PBC patients. © Springer-Verlag Wien 2012.

Aims: Accurate clinical assessment of liver fibrosis is essential and the aim of our study was to compare and combine hemodynamic Doppler ultrasonography, liver stiffness by transient elastography, and non-invasive serum biomarkers with the degree of fibrosis confirmed by liver biopsy, and thereby to determine the value of combining non-invasive method in the prediction significant liver fibrosis. Material and methods: We included 102 patients with chronic liver disease of various etiology. Each patient was evaluated using Doppler ultrasonography measurements of the velocity and flow pattern at portal trunk, hepatic and splenic artery, serum fibrosis biomarkers, and transient elastography. These parameters were then input into a multilayer perceptron artificial neural network with two hidden layers, and used to create models for predicting significant fibrosis. Results: According to METAVIR score, clinically significant fibrosis (≥F2) was detected in 57.8% of patients. A model based only on Doppler parameters (hepatic artery diameter, hepatic artery systolic and diastolic velocity, splenic artery systolic velocity and splenic artery Resistance Index), predicted significant liver fibrosis with a sensitivity and specificity of 75.0% and 60.0%. The addition of unrelated non-invasive tests improved the diagnostic accuracy of Doppler examination. The best model for prediction of significant fibrosis was obtained by combining Doppler parameters, non-invasive markers (APRI, ASPRI, and FIB-4) and transient elastography, with a sensitivity and specificity of 88.9% and 100%. Conclusion: Doppler parameters alone predict the presence of ≥F2 fibrosis with fair accuracy. Better prediction rates are achieved by combining Doppler variables with non-invasive markers and liver stiffness by transient elastography.

Aims: Accurate clinical assessment of liver fibrosis is essential and the aim of our study was to compare and combine hemodynamic Doppler ultrasonography, liver stiffness by transient elastography, and non-invasive serum biomarkers with the degree of fibrosis confirmed by liver biopsy, and thereby to determine the value of combining non-invasive method in the prediction significant liver fibrosis. Material and methods: We included 102 patients with chronic liver disease of various etiology. Each patient was evaluated using Doppler ultrasonography measurements of the velocity and flow pattern at portal trunk, hepatic and splenic artery, serum fibrosis biomarkers, and transient elastography. These parameters were then input into a multilayer perceptron artificial neural network with two hidden layers, and used to create models for predicting significant fibrosis. Results: According to METAVIR score, clinically significant fibrosis (≥F2) was detected in 57.8% of patients. A model based only on Doppler parameters (hepatic artery diameter, hepatic artery systolic and diastolic velocity, splenic artery systolic velocity and splenic artery Resistance Index), predicted significant liver fibrosis with a sensitivity and specificity of 75.0% and 60.0%. The addition of unrelated non-invasive tests improved the diagnostic accuracy of Doppler examination. The best model for prediction of significant fibrosis was obtained by combining Doppler parameters, non-invasive markers (APRI, ASPRI, and FIB-4) and transient elastography, with a sensitivity and specificity of 88.9% and 100%. Conclusion: Doppler parameters alone predict the presence of ≥F2 fibrosis with fair accuracy. Better prediction rates are achieved by combining Doppler variables with non-invasive markers and liver stiffness by transient elastography.

Interest in drug-induced liver injury (DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of LiverTox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain. © 2017 Baishideng Publishing Group Inc. All rights reserved.

Background & Aims: Acute-on-chronic liver failure (ACLF) is characterized by a rapid progression to multiple organ failure and is associated with a very high mortality rate of 50-90%. Novel therapies are being investigated such as Erythropoietin (EPO). The aim of this prospective cohort study was to analyse the value of EPO in predicting prognosis and determine which patients may benefit most from EPO therapy. Methods: According to the EASL-CLIF criteria, 104 consecutive patients were diagnosed with ACLF, and separated into two groups based on the type of insult: bleeding (Group A=31) or non-bleeding (Group B=73). In addition to a complete biochemical work-up and calculation of relevant prognostic scores, levels of EPO were measured on admission and correlated to the type of insult and final outcome. Results: Fifteen patients from Group A (mean age 60.32±9.29 years) had a lethal outcome and higher values of EPO on admission (319.26±326.58 mIU/ml) (p<0.005), compared to the 37 patients from Group B (mean age 59.9±10.19 years) with EPO levels at admission of 29.88±34.6 mIU/mL. In Group B, a cut-off EPO value of 30.65 mIU/mL had a sensitivity of 87.5% and a specificity 57.4% in predicting lethal outcome with an AUROC of 0.823. In Group A, a cut-off value of 229.95 mlU/mL had a sensitivity and specificity of 53.3% and 92.7%, respectively. The AUROC for this cut-off was 0.847. Conclusions: Erythropoietin is superior to the standard prognostic scores in predicting 28-day mortality. Lower levels of EPO were detected in patients without bleeding as an insult indicating a possible therapeutic benefit in these patients. © 2016, Romanian Society of Gastroenterology. All rights reserved.

Villous adenomas are benign epithelial lesions with malignant potential that can occur in any part of the gastrointestinal tract. We present a case of a middle age woman with acromegaly who was investigated for nonspecific gastrointestinal complaints. Ultrasonography and subsequent endosonography diagnosed a large (4.5 cm), hyperechoic, sessile polyp with numerous pedicles. An open cholecystectomy was performed and revealed a villous adenoma with several foci of carcinoma in situ. Detailed investigations showed no other tumors of the gastrointestinal tract. After five years of follow-up, the patient reports no complaints, and the results of laboratory testing and imaging studies are within the normal range. © 2007 The WJG Press. All rights reserved.

Obesity is a growing problem worldwide and disorders associated with excess body fat including the metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease and malignant neoplasms are becoming a major cause of morbidity and mortality. Over the past decade, a vast amount of research has furthered our understanding of non-alcoholic fatty liver disease; however, only recently pancreatic fat infiltration is coming to the forefront of investigation. Termed non-alcoholic fatty pancreas disease (NAFPD), it is becoming evident that it has important associations with other diseases of obesity. It appears to arise as obesity progresses and after an initial phase of pancreatic hypertrophy and hyperplasia, fatty infiltration becomes apparent. Various studies have demonstrated that NAFPD may exacerbate the severity of acute pancreatitis, promote pancreatic dysfunction associated with insulin resistance and T2DM, and even have links to the development of pancreatic carcinoma, and therefore, it must be investigated in further detail. © 2017, BMJ Publishing Group. All Right Reserved.

Background/aims: Portal hypertension and development of esophageal varices is one of the major complications of liver cirrhosis. The aim of our study was to evaluate the possibility of the presence of esophageal varices and their size using biochemical and ultrasonography parameters in patients with alcoholic liver cirrhosis. Material and Methods: We included in our study 86 patients (74 males, mean age 55±7) with alcoholic liver cirrhosis. The control group consisted of 102 patients with cirrhosis of other etiologies. All patients underwent a complete biochemical workup, upper digestive endoscopy and ultrasonography examination. The right liver lobe diameter/albumin and platelet count/spleen diameter ratios were calculated. The correlation of the calculated ratios with the presence and degree of esophageal varices in patients with liver cirrhosis was also determined. Results: The mean value of right liver lobe diameter-albumin ratio was 6.15±1.77, and statistically significantly differed from values determined in the control group (4.97±1.68). The mean platelet count-spleen diameter ratio was 972.5±599.0 in alcoholic liver cirrhosis and 1055.9±821.3 in controls (p>0.05). In patients with alcoholic liver cirrhosis, none of the analyzed noninvasive markers was shown to be a good predictor of the presence and size of esophageal varices. Conclusions: Despite the important role of noninvasive markers in providing information pertinent to determination of esophageal varices in patients with liver cirrhosis, these markers have limited relevance in patients with alcoholic cirrhosis.

Helicobacter pylori (H. pylori ) plays a role in the patho genesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence: (1) eradication of the already present infection; and (2) immunization (prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available. © 2015 Baishideng Publishing Group Inc. All rights reserved.

Background: Data suggest cystatin C (CysC) levels and hepatic artery resistive index (HARI) correspond to the progression of chronic liver disease. We aimed to evaluate the clinical significance of these parameters in assessment of fibrosis in patients with liver cirrhosis. Methods: The cross-sectional study included 63 patients with liver cirrhosis. A control group consisted of 30 age-and gender-matched healthy persons. Results: We confirmed significantly higher values of CysC in patients with cirrhosis compared to control group (p = 0.036). Average value of HARI in the examined group was increased (0.72 ± 0.06) and there was the statistically significant difference compared to controls (0.66 ± 0.03) (p < 0.001). We found statistically significant correlation between HARI and CysC in the study group. Analyzing the possibility of distinguishing healthy subjects from patients with fibrosis, we have found that the area under the curve is far greater in the HARI index than CysC. Comparison of CysC among Child–Pugh stages and correlation with a model for end-stage liver disease (MELD) score showed statistically significant results. Conclusion: We confirmed HARI is a more accurate parameter than CysC in discriminating healthy subjects from patients with fibrosis, while CysC could be a better indicator of the stage of liver cirrhosis. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Objective: Research on inflammatory bowel disease (IBD) has highlighted genes involved in the regulation of inflammatory responses as contributors to disease pathogenesis. This study aimed to evaluate the associations between IBD and variations in NOD2, TLR4, TNF-α, IL-6, IL-1β and IL-1RN genes, and to use the genetic data obtained in predictive modeling. Methods: A total of 167 IBD patients and 101 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Using the genotype data attained as the input to various classification algorithms, IBD prediction models were designed. The area under the receiver operating characteristic curve (AUROC) was used to measure their performance. Results: Significant associations were found between Crohn's disease (CD) and minor NOD2 variants, as well as TLR4 299Gly, TNF-α G-308A, IL-6 G-174C and IL-1RN VNTR A2 variants, while ulcerative colitis (UC) was associated only with IL-1RN VNTR A2 variants. CD and UC showed highly significant difference in the allelic distribution of TNF-α G-308A, where the A allele was found to be related to CD, and the G allele to UC. A combined effect of patients' gender and TLR4 variants was observed among CD patients. When all analyzed genotype and gender data were used, prediction performance achieved a maximum AUROC of 0.690 for CD and 0.601 for UC dataset. Conclusion: Variations in the genes involved in immune regulation are genetic factors of importance in IBD susceptibility that could potentially be used as predictors of disease development. © 2015 John Wiley & Sons, Ltd.