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A. Husic-Selimovic, J. Huskic, Z. Vukobrat-Bijedic, R. Mesihović, M. Gribajčević

The role of ferritin in fibrogenesis of liver parenchyma in patients with alcoholic liver disease has been investigated in previous studies. Ferritin was shown to be an indirect marker of ferum deposition in liver parenchyma in alcohol liver disease. The aim of the present study was to examine the role of nitric oxide (NO) in the pathogenesis of alcoholic liver disease as well as the influence of NO on iron (ferritin) metabolism in patients with alcoholic liver disease. Serum concentrations of NO and iron markers (iron, total iron binding capacity, ferritin) were measured in 30 male patients (aged 20-60 years) with alcoholic liver disease, as well as from a control group (30 male patients (aged 20-60 years) without liver disease). NO concentration was detected by measuring production of nitrates and nitrites using classical colorimetric Griess reactions. There was a statistically significant increase in serum NO concentration in patients with alcoholic liver disease compared to the control group (mean +/- SEM; 41,2 +/- 25,3 vs. 28,9 +/- 12,3 mmol/dm3, respectively; p<0,03). Similarly, serum iron levels (18,7 +/- 8,2 vs. 13,2 +/- 10,2 g/100 cm3, respectively; p<0,03) and serum total iron binding capacity (51,3 +/- 13,9 vs. 41,4 +/- 11,4 micromol/dm3, respectively; p<0,005) were also significantly higher in patients with alcoholic liver disease compared to control patients. The serum concentration of ferritin was 27% higher in patients with alcoholic liver disease than in the control group; however this was not statistically significant (283,2 +/- 291,0 vs. 222,9 +/- 252,0 g, respectively; p<0,4). There was no correlation between NO and ferritin in the investigated groups. These results suggest a possible role of NO and iron in the pathogenesis of alcoholic liver disease. NO and iron may be used as non-invasive predictors of liver damage. Also the role of iron in sera, and its deposition in liver parenchyma, could be used in clinical practice, especially in regards to assessing the fibrogenesis of liver parenchyma induced by ferritin.

P. Urbánek, M. Oltman, L. Ivanovski, V. Řehák, M. Gribajčević, D. Messinger, A. Tietz, P. Husa

R. Mesihović, N. Vanis, A. Mehmedović, S. Gornjakovic, M. Gribajčević

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.

A. Husic-Selimovic, J. Huskic, Z. Vukobrat-Bijedic, R. Mesihović, M. Gribajčević

Th e role of ferritin in fi brogenesis of liver parenchyma in patients with alcoholic liver disease has been investigated in previous studies. Ferritin was shown to be an indirect marker of ferum deposition in liver parenchyma in alcohol liver disease. Th e aim of the present study was to examine the role of nitric oxide (NO) in the pathogenesis of alcoholic liver disease as well as the infl uence of NO on iron (ferritin) metabolism in patients with alcoholic liver disease. Serum concentrations of NO and iron markers (iron, total iron binding capacity, ferritin) were measured in  male patients (aged – years) with alcoholic liver disease, as well as from a control group ( male patients (aged – years) without liver disease). NO concentration was detected by measuring production of nitrates and nitrites using classical colorimetric Griess reactions. Th ere was a statistically signifi cant increase in serum NO concentration in patients with alcoholic liver disease compared to the control group (mean ± SEM; , ± , vs. , ± , mmol/dm, respectively; p<,). Similarly, serum iron levels (, ± , vs. , ± , g/ cm, respectively; p<,) and serum total iron binding capacity (, ± , vs. , ± , μmol/dm, respectively; p<,) were also signifi cantly higher in patients with alcoholic liver disease compared to control patients. Th e serum concentration of ferritin was  higher in patients with alcoholic liver disease than in the control group; however this was not statistically signifi cant (, ± , vs. , ± , g, respectively; p<,). Th ere was no correlation between NO and ferritin in the investigated groups. Th ese results suggest a possible role of NO and iron in the pathogenesis of alcoholic liver disease. NO and iron may be used as non-invasive predictors of liver damage. Also the role of iron in sera, and its deposition in liver parenchyma, could be used in clinical practice, especially in regards to assessing the fi brogenesis of liver parenchyma induced by ferritin.

R. Mesihović, N. Vanis, M. Gribajčević

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.

R. Mesihović, N. Vanis, M. Gribajčević

Patients with verified early stage of the esophageal carcinoma are presented with a very good prognosis, however all over the world patients present themselves with advanced stages thus minoring the chances for survival. Data obtained form the USA programmes are presenting information about 5 year survival period in 14% of the cases. On the other hand, prospective multi centric European study refers to the same period in 10%. UK studies are presenting age-standardized relative rate of survival at 25% for the first 2 years and corresponding 4,8%-6,3% for the 5 year period. Prognoses are deteriorating with the progression of the primary tumor, thus patients in stage IV are facing 5 year survival period in less than 5 % of the cases. 5 year survival period for patients, who underwent surgery in N0 stage, is 40%-60% comparing to 5%-17% for those in confirmed N1 stage. Patients who undergo surgery in confirmed T3N1 stage are faced with 5 year survival period in 8%-10% of the cases, emphasizing the fact that these tumors are operable, but rarely curable by surgery itself. Neo adjuvant therapy use is increasing for the patients in stages IIB and IIC (local progression of the tumor), aiming to decrease the size of the primary cancer prior to surgery thus increasing the rate of long term survival. Our experiences brought out in this study correlate with the foreign results thus aging stressing the fact that the exact staging of the tumor is the basics for the treatment as well as the right choice of the patients for surgery treatment, and those who need neo adjuvant therapy.

Endoscopic ultrasound (EUS) and Magnetic Endoscopic Cholangiopancreatography (MRCP) are important supplementary methods used for endoscopic extraction of common bile duct stones. The technical characteristics of both methods are excellent. If EUS is used for diagnostic purposes in diagnostic of biliary tree disorders there are almost no adverse consequences compared with other indication for this method. Nevertheless, the results are related to experience of physician. Advance of EUS compared to MRCP is its sensitivity and specificity even in cases where stones are small and dilation of biliary tract is minor. The role of EUS and ERCP in reveal of biliary tree stones and disorders is clearly defined. Comparasion of these two methods should be prospective and used in cases where definitive diagnosis is unclear. If EUS reveal stones in biliary tree then ERCP should be done in same session. Beside its role in excluding biliary pancreatitis, EUS can be used for examination of patient with acute and recurrent pancreatitis and is excellent for revealing ductal and parenchymal abnormalities of pancreas.

R. Mesihović, N. Vanis, A. Husic-Selimovic, D. Prohić, M. Gribajčević, H. Tanović, Š. Bešlić, F. Smajlović et al.

INTRODUCTION Endoscopic ultrasonography (EUS) is a well-established method of evaluating patients with gastrointestinal diseases, especially malignancies. EUS is like other similar endoscopy techniques, based on high frequency ultrasonography. This high level technology allows examination of tissue to almost microscopic level, not only in digestive system but its surrounding structures. OBJECTIVE The aim of this study was to determine the contribution of endoscopic experience, based on the number of endosopic ultrasonography examination performed in the three years period, to obtain 80% diagnostic accuracy with staging of the disease in order to achieve a 30-60% change rate in treatment decisions which is accepted standard. RESULTS First group with 210 patients was examined in the first year of work; 325 examined in the second year of work and 295 in the third year. DIAGNOSTIC Accuracy in the first year of work, were 45% (p<0.001 for the choledocholithiasis; p=0.197 for the pancreatic cancer; p=0.195 for LN detection in the gastric cancer). In the second year of work diagnostic accuracy were 78%/p=0.550 for the choledocholithiasis; p=0.228 for the pancreatic cancer; p=0.503 for LN detection in the gastric cancer/. Diagnostic accuracy in the third year of work were 81%/p<0.001 for the choledocholithiasis; p=0.018 for the pancreatic carcinoma; p=0.042 LN detection in the gastric cancer/. CONCLUSION Application of Endoscopic ultrasonography in diagnostics, based on number of EUS examination performed, after three years of work, achieved 80% diagnostic accuracy, compared to standard imaging methods and results of surgery in staging of the disease. EUS results made a change in treatment decisions in 30-60% of patients which is world standard and completely justify use of endoscopic ultrasonography in clinical practice.

R. Mesihović, D. Prohić, M. Gribajčević, N. Vanis, S. Gornjakovic, Aida Sarac

Portal hypertenisive gastropathy (PHG) and GAVE syndrome are recently discovered entities who can be associated with bloodloss from gastrointestinal tract at patients with or without liver cirrhosis. PHG will be developed at 65% of patients with portal hypertension caused by liver cirrhosis but it could be developed at portal hypertension which is not caused by the liver cirrhosis. PHG is often assosiated with portal hypertension patients and presence of esofageal and /or gastric varices. Mechanism of pathogenesis PHG is still not completely cleared up, but regulation of gastric nitric oxide level, postaglandins, tumor necrosis factor (TNF) and epidermal growth factor production could be important factors in development of portal hypertensive gastropathy. Mechanisms who participate in originating of Gastric Antral Vascular Ectasia (GAVE) are also not completly clear. Classic characteristics of this syndrome are red, often haemorrhagic lesions most often located in stomach antrum, and who could result in blood loss. More than 70% of patients with GAVE syndrome have no cirrhosis or portal hypertension. But when liver cirrhosis is present, it is very difficult to make difference between GAVE and PHG. This review will be focused on incidence, clinical importance, etiology, pathofisiology and treatment of PHG, and how to differentiate between GAVE syndrom and PHG in a case that there exists.

R. Mesihović, M. Gribajčević, N. Vanis, F. Smajlović

AIMS The EUS is a minimally invasive method, with a most specificness and sensitivity in verification of concrements in choledochus. The aim of this study is to compare the findings of conventional ultrasound with radial EUS in diagnosis of choledocholithiasis. PTS AND METHODS: 2o pts were included in the study, 13 females. All pts were under susceptibility of concrement presence in choledoch. From 32 examinees in 13 by the none methods was confirmed that they have the obstruction of this ethiolology. The rest 19 examinees underwent endoscopy by an experienced endosonographyst, completely independent of eventual findings by conventional US. Comparative method was done by an ultrasonographer, also uninformed of earlier procedures. RESULTS 5/20 pts (25%), were excluded from the study. 5/15 pts (33%) were females. Nine (60%) pts (2 males) examined by EUS, showed a presence of concrements in a choledoch, its size varying from 1 x 1 mm to 16 x 6 mm. US provided a very similar results, with minimal differences in the size of concrements (t = 1,706; p < 0.10). In 3 pts the EUS determined a presence of concrements in choledoch, with sizes varying from 1.5 mm to 4 mm, whilst US showed a susceptible changes with recommendation for further analysis. The EUS findings in 3 patients verified a small concrements in choledoch, while standard US did not show presence of these concrements. It is necessary to underline that last three patients underwent cholechistecthomy. CONCLUSION The radial EUS is a preferred method with excellent performance in verification of choledocholithiasis.

M. Gribajčević, N. Vanis, R. Mesihović

AIM Prospective clinical investigation efficacy of omeprazole was proved in combination with two antibiotics (azithromicine and amoxycillin) in H. pylori eradication. Efficacy of omeprazole was also followed in gastric and duodenal ulcer healing. PATIENTS AND METHODS Patients with dyspepsia and peptic ulcer of stomach and duodenum were examined. Positive H. pylori status was proved by rapid urease test (Pronto dry). During first 7 days patients were treated with omeprazole (Ulzol caps. 2 x 20 mg), amoxycillin 7 days (Amoxil 2 x 1000 mg), and Azithromicin 3 days (Sumamed 1 x 1000 mg). After that period patients received omeprazole (Ulzol caps. 1 x 20 mg) in single morning dose next 21 or 28 days in continuation of antisecretory treatment. Control endoscopy revealed rate of ulcer healing and rate of H. pylori infection with same test at least 28 days after initiation of treatment. RESULTS Complete eradication of H. pylori was in 46/50 (92%) patients (p < 0.001), complete ulcer healing in 48/50 (96%) patients. No patients had complication after omeprazole treatment. Two patients (4%) had worsening of dyspepsia, but without treatment discontinuation. CONCLUSION Triple treatment with omeprazole, azithromicin and amoxycillin achieved high rate of H. pylori eradication, gastric and duodenal ulcer healing. Treatment was well tolerated, with rapid pain and dyspepsia symptoms relief.

M. Gribajčević, S. Gornjaković, N. Vanis

Gastroscopy is medical procedure which allows examination of esophagus, stomach and duodenum by flexible instrument named gastroscope. Procedure could be strictly diagnostical, with evidence of current state and interventional/therapeutical, by attempting of prompt action (haemostasis, mucosal resection of cancer "in situ", polypectomy, dilation of benign and malignant strictures of digestive tube, placing endoprosthesis over strictures) Despite of its invasive nature, endoscopy is daily routine, safe and accurate procedure.

N. Vanis, M. Gribajčević, R. Mesihović, S. Gornjaković

Examination of lower part of digestive system by colonoscopy is necessity in occult fecal hemorrhage occurrence, hematochesis, unresolved loss of blood iron and suspicious finding of large bowel X-ray barium study. By therapeutical colonoscopy, haemorrhage from neoplasms and angiodysplastic changes are controlled, foreign bodies are removed as well as routine polipectomics. Balloon dilation of large bowel stenosis, and palliative treatment of unoperable stenoses lead to improvement in quality of life with significant cost-benefit effects. Follow-up of patients on high-risk for colorectal neoplasms increased early diagnosis of neoplasms.

The gastroesophageal reflux disease (GERB) is one from the most frequent disease of the upper gastrointestinal system. Extraesophageal manifestations GERB occur most often as lung manifestations, ORL discomforts, and as noncardial pain in breasts. GERB is associated with the various respiratory diseases and symptoms as are the bronchial asthma, cough, wheezing. The episodes of the sour reflux into the esophagus, specially in children, can provoke the symptoms discapper mainly in all patients who have used the antisecretoral therapy.

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