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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.

R. Dobrila-Dintinjana, M. RadiÄ, M. Dintinjana, A. RedzoviÄ, J. VukeliÄ, M. Zelić, N. Vanis, D. TrivanoviÄ

Cancer Cachexia-Anorexia Syndrome (CACS) is a common and often underdiagnosed syndrome in cancer population. If undiagnosed, this initially reversible syndrome leads to deterioration and is direct cause of death in 20% of cancer patients. Oppositely, with timely diagnosis, nutritional counseling can help to slow the progression and positively influence on quality of life, tolerance to chemotherapy with ultimate goal of prolonging patient’s life. Colorectal and pancreatic cancers are very common tumors type worldwide. The prognosis for the survival in pancreatic cancer is poor as in colorectal after disease progression. Cancer anorexia-cachexia syndrome is highly prevalent among patients with colorectal and pancreatic cancer, and has a large impact on morbidity and mortality, and on patient quality of life. The etiology of primary CACS appears to be related to the pathological loss of inhibitory control of catabolic pathways, whose increased activities are not counterbalanced by the increased central and peripheral anabolic drive. Secondary CACS (related to gastrointestinal obstruction, vomiting due to chemotherapy etc.) is contributing to bad patient’s condition. As a result of being complex and influencing a great number of metabolic pathways, cancer cachexia can be treated in multimodal manner. In this review we are presenting most promising targets and current opinions in ways to treat cachexia and our results with nutritional supplementation in colorectal and pancreatic cancer patients.

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.

R. Dobrila-Dintinjana, N. Vanis, M. Dintinjana, M. Radić

Pancreatic cancer is the fourth leading cause of cancer death overall. The factors that favor the development of pancreatic cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a "multi-hit" hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and programmed cell death (apoptosis). The most common mutations involve K-ras gene, epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by using pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact on carcinogenesis.

R. Dobrila-Dintinjana, Jelena Vukelic, M. Dintinjana, N. Vanis, A. Ružić, M. Brkljačić-Žagrović, S. Pleština, Z. Kolić

R. Dobrila-Dintinjana, D. Trivanović, M. Dintinjana, Jelena Vukelic, N. Vanis

Renata Dobrila-Dintinjana1, Dragan Trivanovic2, Marijan Dintinjana3, Jelena Vukelic4 and Nenad Vanis5 1Department of Radiation Oncology, Clinical Hospital Center Rijeka, University of Rijeka, School of Medicine, 2General Hospital Pula, Department of Internal Medicine, 3Clinic of General Medicine Dr Dintinjana, 4Department of Speech and Hearing Disorders Diagnostics and Rehabilitation, Clinical Hospital Center Rijeka, 5Division for Gastroenterology and Hepatology, Clinical Center University of Sarajevo, Faculty of Medicine, University of Sarajevo, 1,2,3,4Croatia 5Bosnia and Herzegovina

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.

Aida Saray, R. Mesihović, N. Vanis, S. Gornjakovic, D. Prohić

OBJECTIVE To determine different haemostatic tests in patients with various degrees of liver parenchymal damage and to rule out their role in assessing parenchymal hepatocyte dysfunction. METHODS Seventy-five patients with chronic liver disease were included and due to their degree of liver damage categorized into three groups: group one patients with chronic viral hepatitis and early stage of fibrosis (n=30), group two patients with compensated cirrhosis (n=17) and group three patients with decompensated liver cirrhosis (n=28). The following haemostatic tests were measured: activated partial thromboplastin time, prothrombin time, plasma fibrinogen, antithrombin III and protein C and plasma D-dimer. RESULTS Antithrombin III levels showed significant reduction in compensated (83.86 +/- 19.49%) and decompensated cirrhosis (52.64 +/- 14.31%; p < 0.001), while protein C activity exhibited significant decrease in all the patients group, including patients with chronic viral hepatitis (90.58 +/- 11.03, 74.65 +/- 19.56, 41.11 +/- 18.35%; p < 0.001) in comparison with controls. Correlation between antithrombin III (Pearson ro = -.931, p < 0.01) and protein C (Pearson ro = -.789, p < 0.01) and clinical degree of chronic liver disease were found. D-dimer levels were significantly increased in decompensated cirrhosis (832.26 +/- 537.19 microg/L; p < 0.001) and no significant difference was found in group two and three when compared with healthy controls. CONCLUSIONS In advanced chronic liver disease anticoagulant activitiy may reflect hepatocellular dysfunction. Protein C activity may be used as a senstive marker of hepatocellular damage even in those patients with mild liver affection whereas D-dimer levels may be considered as an important sign of decompensation in cirrhotic patients. Further studies are necessary to approve whether these parameters could be used as clinical routine markers of hepatocyte function in chronic liver disease.

BACKGROUND Peptic ulcer bleeding is a common and potentially fatal condition. For patients with bleeding peptic ulcers that display major endoscopic stigmata of recent hemorrhage, a combination of endoscopic and pharmacologic therapy is the current standard management. OBJECTIVE To show our experience with management of peptic ulcer bleeding. PATIENTS Patients who presented with gastrointestinal bleeding caused by peptic ulcer or recent history (< 24 h before presentation) of hematemesis and/or melena admitted to our hospital emergency departments, and patients whose ulcer hemorrhage started after hospitalization for an unrelated medical or surgical condition. METHODS Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or endoscopic hemoclips, and randomized to receive intravenous pantoprasole according to the continuous regimen (dose of 5 x 40 mg in continuous infusion of 8 mg/h for 72 h) or the standard regimen (40 mg bolus of PPI twice daily for 3 days). After the infusion, all patients were given 40 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as discovered by the repeated endoscopy. RESULTS Bleeding recurred in 5 of 34 patients (14.7%) receiving the intensive regimen, and in 8 of 35 (22.8%) patients receiving the standard regimen. Hemoglobin (g/l) rate in standard regimen group was 93.5 +/- 23.8, and in intensive regimen group 106.6 +/- 22.4 (P = 0.042). Mean units of blood transfused for all patients in group were 71.8 +/- 45.8 in the intensive and 45.3 +/- 50.2 in the standard regimen group (P = 0.0257). The duration of hospital stay was 6.4 +/- 2.8 in standard group and 5.8 +/- 2.8 in the intensive group (P = 0.40). CONCLUSIONS In patients with bleeding peptic ulcers with successful endoscopic hemostasis the standard PPI regimen had advantage on transfusion requirements, but no advantage with respect to in-hospital rates of rebleeding rates, need for surgery, length of hospital stay, or death, which corresponds with recent studies.

INTRODUCTION Colorectal cancer is one of the most common forms of cancer and its frequency has been on the constant and significant increase over the past 20 years. Prevention aiming for early precancerous detection, results in huge financial savings in the health care system. METHODOLOGY AND TEST SUBJECTS: Prospective randomized clinical research was conducted on 150 randomly chosen asymptomatic persons over the age of 50, with positive family history. All test subjects were given a Haemoccult test and colonoscopy examination. Primary objective of the research was to detect precancerous symptoms of colorectal cancer or large intestine cancer in the early stage of the disease when it is therapeutically curable. Secondary objective was to prove that colonoscopy represents an obligatory examination of the large intestine, as well as to introduce a Haemoccult test as a regular diagnostic procedure on the level of primary and secondary health care for asymptomatic patients over the age of 50. RESULTS Out of 80/230 test subjects who did not fully complete the examination, 62 (77.5%) did not respond to the test reading for obscure bleeding, whereas 18 of them did not consent to be given a colonoscopy examination. Two registered neoplasm were found in the rectosigmoid colon, and the polyps were found in rectosigmoid colon in over 2/3 of the patients. In 125/150 test subjects, the test for obscure bleeding was negative (p < 0.001), but the colonoscopy procedure proved that 11 patients had precancerous changes (polyps). This proved that the test was not highly sensitive and it was recommended that it should be conducted in combination with colonoscopy. Patients with positive test (n = 14) had 8 normal colonoscopy results, but the difference was not significant. CONCLUSION Application of the test for detection of obscure bleeding once a year, in combination with flexible colonoscopy every 5 years, significantly reduces the risk of colorectal cancer inception.

S. Jovanovic-Cupic, G. Stamenković, J. Blagojević, N. Vanis, B. Stanojević, L. Berberović

The distribution of ABO blood groups and the Rhesus factor was analyzed in 279 patients who suffered from malignant tumors of the digestive system. Patients were registered retrospectively in the Gastroenterohepatology Clinic, Clinical Center, University of Sarajevo over a discontinuous period of 88 months. From the results obtained, it was con- cluded that: (a) men became ill from gastric cancer significantly more frequently than women; (b) the frequency of liver carcinoma was three times higher than the global frequency and the frequency neighboring ethnic groups; and (c) patients with blood group B and patients with RhD(-) exhibited a significantly higher proportion of disease.

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