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| 1 | Pathogenesis and management issues for non-alcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed 'two hit' model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-κB-dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual. | Marko Duvnjak Ivan Leroti Neven Bari Vedran Tomai Lucija Virovi Juki Vedran Velagi | 2007 | World Journal of Gastroenterology2007，13，34： | 74 |
| 2 | Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD)is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis.The pathogenesis of NAFLD and nonalcoholic steatohepatitis(NASH)has not been fully elucidated.The'two-hit'hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH.It should be better regarded as a multiple step process,with accumulation of liver fat being the first step,followed by the development of necroinflammation and fibrosis.Adipose tissue,which has emerged as anendocrine organ with a key role in energy homeostasis,is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins.These adipocyte-specific or enriched proteins,termed adipokines,have been shown to have a variety of local,peripheral,and central effects.In the current review,we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD.We particularly focus on adiponectin,leptin and ghrelin,with a brief mention of resistin,visfatin and retinol-binding protein 4 among adipokines,and tumor necrosis factor-α,interleukin(IL)-6,IL-1,and briefly IL-18 among proinflammatory cytokines.We update their role in NAFLD,as elucidated in experimental models and clinical practice. | Sanja Stojsavljevi? Marija Gomer?i? Pal?i? Lucija Virovi? Juki? Lea Smir?i? Duvnjak Marko Duvnjak | 2014 | World Journal of Gastroenterology2014，20，48： | 42 |
| 3 | Role of Ki-67 as a prognostic factor in gastrointestinal stromal tumors显示文摘AIM:To investigate primarily the prognostic value of Ki-67,as well as other parameters,in gastrointestinal stromal tumors(GISTs).METHODS:Ki-67,c-KIT,platelet-derived growth factor receptor-alpha(PDGFRα),smooth muscle actin(SMA),CD34,S100 were stained for immunohistochemistry which was performed on formalin-fixed,paraffinembeded sections on representative block from each case.Proliferation index counted by Ki-67 antibody was calculated as a number of positive nuclear reaction over 100 cells.Immunoreactivity for c-KIT and PDGFRα was evaluated semiquantitatively(weak,intermediate,strong) and for c-KIT type of reactivity was analyzed(cytoplasmic,membrane and 'dot-like' staining).Immunoreactivity for SMA,CD34 and S100 were was evaluated as positive or negative antigen expression.Pathologic parameters investigated in this study included tumor size,cell type(pure spindle,pured epitheloid mixed spindle and epitheloid),mitotic count,hemorrhage,necrosis,mucosal ulceration.Clinical data included age,gender,primary tumor location and spread of disease.χ 2 test and Student's t-test were used for comparisons of baseline characteristics.The Cox's proportional hazard model was used for univariable and multivariable analyses.Survival rates were calculated by Kaplan-Meier method and statistical significance was determined by the log-rank test.RESULTS:According to the stage of disease,there were 36 patients with localized disease,29 patients with initially localized disease but with its recurrence in the period of follow up,and finally,35 patients had metastatic disease from the very beginning of disease.Tumor originated most commonly in the stomach(41%),small intestine was the second most common location(36%).The mean size of primary tumors was 6.5 cm.The mean duration of follow-up was 60 mo.Multiple parameters were analyzed for their effect on overall survival,but no one reached statistical significance(P = 0.06).Analysis of time to progression/relapse in initially localized disease(univariate analysis),tumor size,mitotic count,Ki-67 and type of d-KIT distribution(cytoplasmic vs membrane/'dot-like') showed statistically significant correlation.In multivariate analysis in the group of patients with localized disease,there were only 2 parameters that have impact on relapse,Ki-67 and SMA(P < 0.0001 and P < 0.034,respectively).Furthermore,Ki-67 was analyzed in localized diseasevs localized with recurrence and metastatic disease.It was shown that there is a strict difference between these 2 groups of patients(median value was 2.5 for localized disease vs 10.0 for recurrent/metastatic disease,P < 0.0001).It was also shown that the cut-off value which is still statistically significant in terms of relapse on the level of 6%.The curves for survival on that cut-off level are significantly different(P < 0.04,Cox F).CONCLUSION:Ki-67 presents a significant prognostic factor for GIST recurrence which could be of great importance in evaluating malignant potential of disease. | Borislav Belev Iva Bri Juraj Prejac Zrna Antunac Golubi Damir Vrbanec Jadranka Bozikov Ivan Aleri Marko Boban Jasminka Jaki Razumovi | 2013 | World Journal of Gastroenterology2013，19，4： | 14 |
| 4 | Overview and developments in noninvasive diagnosis of nonalcoholic fatty liver disease显示文摘High prevalence of non-alcoholic fatty liver disease (NAFLD) and very diverse outcomes that are related to disease form and severity at presentation have made the search for noninvasive diagnostic tools in NAFLD one of the areas with most intense development in hepatology today.Various methods have been investigated in the recent years,including imaging methods like ultrasound and magnetic resonance imaging,different forms of liver stiffness measurement,various biomarkers of necroinflammatory processes (acute phase reactants,cytokines,markers of apoptosis),hyaluronic acid and other biomarkers of liver fibrosis.Multicomponent tests,scoring systems and diagnostic panels were also developed with the purposes of differentiating non-alcoholic steatohepatitis from simple steatosis or discriminating between various fibrosis stages.In all of the cases,performance of noninvasive methods was compared with liver biopsy,which is still considered to be a gold standard in diagnosis,but is by itself far from a perfect comparative measure.We present here the overview of the published data on various noninvasive diagnostic tools,some of which appear to be very promising,and we address as well some of still unresolved issues in this interesting field. | Neven Bari Ivan Leroti Lea Smiri-Duvnjak Vedran Tomai Marko Duvnjak | 2012 | World Journal of Gastroenterology2012，18，30： | 7 |
| 5 | Genetic polymorphisms in non-alcoholic fatty liver disease:Clues to pathogenesis and disease progression显示文摘The spectrum of non-alcoholic fatty liver disease(NAFLD) ranges from simple steatosis through steatohepatitis to advanced f ibrosis and cirrhosis.Although the reason why only a minority of patients develop progressive forms of disease still remains largely unclear,recent research has identified genetic factors as a possible basis for this variation in disease presentation.Most of the studies have been focused on f inding associations between advanced disease forms and selected single nucleotide polymorphisms in genes encoding various proteins involved in disease pathogenesis.Although there are many limitations regarding the study design and interpretation of published data,further carefully planned studies together with implementation of new genetic technologies will likely bring new insights into disease pathogenesis and potential benefits to the management of patients with NAFLD. | Marko Duvnjak Neven Bari Vedran Tomai Ivan Leroti | 2009 | World Journal of Gastroenterology2009，15，48： | 4 |
| 6 | Biliary leakage after urgent cholecystectomy: Optimization of endoscopic treatment显示文摘AIM: To investigate the results of endoscopic treatment of postoperative biliary leakage occurring after urgent cholecystectomy with a long-term follow-up.METHODS: This is an observational database study conducted in a tertiary care center. All consecutive patients who underwent endoscopic retrograde cholangiography(ERC) for presumed postoperative biliary leakage after urgent cholecystectomy in the period between April 2008 and April 2013 were considered for this study. Patients with bile duct transection and biliary strictures were excluded. Biliary leakage was suspected in the case of bile appearance from either percutaneous drainage of abdominal collection or abdominal drain placed at the time of cholecystectomy. Procedural and main clinical characteristics of all consecutive patients with postoperative biliary leakage after urgent cholecystectomy, such as indication for cholecystectomy, etiology and type of leakage, ERC findings and post-ERC complications, were collected from our electronic database. All patients in whom the leakage was successfully treated endoscopically were followed-up after they were discharged from the hospital and the main clinical characteristics, laboratory data and common bile duct diameter were electronically recorded. RESULTS: During a five-year period, biliary leakage was recognized in 2.2% of patients who underwent urgent cholecystectomy. The median time from cholecystectomy to ERC was 6 d(interquartile range, 4-11 d). Endoscopic interventions to manage biliary leakage included biliary stent insertion with or without biliary sphincterotomy. In 23(77%) patients after first endoscopic treatment bile flow through existing surgical drain ceased within 11 d following biliary therapeutic endoscopy(median, 4 d; interquartile range, 2-8 d). In those patients repeat ERC was not performed andthe biliary stent was removed on gastroscopy. In seven(23%) patients repeat ERC was done within one to fourth week after their first ERC, depending on the extent of the biliary leakage. In two of those patients common bile duct stone was recognized and removed. Three of those seven patients had more complicated clinical course and they were referred to surgery and were excluded from long-term follow-up. The median interval from endoscopic placement of biliary stent to demonstration of resolution of bile leakage for ERC treated patients was 32 d(interquartile range, 28-43 d). Among the patients included in the follow-up(median 30.5 mo, range 7-59 mo), four patients(14.8%) died of severe underlying comorbid illnesses.CONCLUSION: Our results demonstrate the great efficiency of the endoscopic therapy in the treatment of the patients with biliary leakage after urgent cholecystectomy. | Neven Ljubii Alen Bianin Tajana Pavi Marko Nikoli Ivan Budimir August Miji Ana Duzel | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，5： | 3 |
| 7 | Endoscopic ultrasound elastography strain histograms in the evaluation of patients with pancreatic masses显示文摘AIM: To investigate the accuracy of the strain histogram endoscopic ultrasound(EUS)-based method for the diagnostic differentiation of patients with pancreatic masses. METHODS: In a prospective single center study, 149 patients were analyzed, 105 with pancreatic masses and 44 controls. Elastography images were recorded using commercially available ultrasound equipment in combination with EUS linear probes. Strain histograms(SHs) were calculated by machine integrated software in regions of interest and mean values of the strain histograms were expressed as Mode 1(over the mass) and Mode 2(over an adjacent part of pancreatic tissue, representing the reference area). The ratio between Mode 2 and Mode 1 was calculated later, representing a new variable, the strain histogram ratio. After the final diagnosis was established, two groups of patients were formed: a pancreatic cancer group with positive cytology achieved by fine needle aspiration puncture or histology after surgery(58 patients), and a massforming pancreatitis group with negative cytology and follow-up after 3 and 6 mo(47 patients). All statistical analyses were conducted in SPSS 14.0(SPSS Inc., Chicago, IL, United States).RESULTS: Results were obtained with software for strain histograms with reversed hue scale(0 represents the hardest tissue structure and 255 the softest). Based on the receiver operating characteristics(ROC) curve coordinates, the cut-off point for Mode 1 was set at the value of 86. Values under the cut-off point indicated the presence of pancreatic malignancy. Mode 1 reached 100% sensitivity and 45% specificity with overall accuracy of 66%(95%CI: 61%-66%) in detection of pancreatic malignant tumors among the patients with pancreatic masses. The positive and negative predictive values were 54% and 100%, respectively. The cut-off for the new calculated variable, the SH ratio, was set at the value 1.153 based on the ROC curve coordinates. Values equal or above the cut-off value were indicative of pancreatic malignancy. The SH ratio reached 98% sensitivity, 50% specificity and an overall accuracy of 69%(95%CI: 63%-70%). The positive and negative predictive values were 92% and 100%, respectively.CONCLUSION: SH showed high sensitivity in pancreatic malignant tumor detection but disappointingly low specificity. Slight improvements in specificity and accuracy were achieved using the SH ratio. | Dalibor Opa?i? Nadan Rustemovi? Mirjana Kalauz Pave Marko? Zvonimir Ostoji? Matea Majerovi? Iva Ledinsky Ana Vi?nji? Juraj Krznari? Milorad Opa?i? | 2015 | World Journal of Gastroenterology2015，21，13： | 3 |
| 8 | Low-grade fibromyxoid sarcoma of the liver: A case report显示文摘BACKGROUND Low grade fibromyxoid sarcoma(LGFMS)is a rare and benign mesenchymal tumor with indolent course,most commonly found in young or middle-aged men.The majority of the LGFMSs are located in the trunk and deep soft tissue of the lower extremities.They appear as well circumscribed,although not encapsulated,which often leads to incomplete surgical resection.Despite their seemingly benign appearance,these tumors have aggressive behavior with high metastatic and recurrence rates.Accurate histopathologic examination of the specimen and its immunohistochemical analysis are mandatory for a precise diagnosis.CASE SUMMARY We report a case of a 38 year-old-man who presented with jaundice and upper abdominal discomfort.Multi-detector computed tomography and magnetic resonance imaging showed a large left liver tumor mass,extending to the hepatoduodenal ligament.Left hepatectomy was performed with resection and reconstruction of hepatic artery and preservation of middle hepatic vein.Histopathologic examination confirmed the tumor being a low-grade fibromyxoid sarcoma.Three and a half years after surgery,the patient died after being diagnosed with spine metastasis.CONCLUSION Due to poor response to all modalities of adjuvant treatment,we consider that the focus of treatment should be on surgery as the only option for curing the disease. | Vladimir Dugalic Igor I Ignjatovic Jelena Djokic Kovac Nikola Ilic Jelena Sopta Slavenko R Ostojic Dragan Vasin Marko D Bogdanovic Igor Dumic Tamara Milovanovic | 2021 | World Journal of Clinical Cases2021，9，1： | 1 |
| 9 | Asymmetric Dihydroxylation via Ligand-Accelerated Catalysis 显示文摘 | E N Jacobsen I Marko W S Mungall | 1988 | J AmChem Soc1988，110，： | 1 |
| 10 | Glycerol reforming in supercritical water; a short review显示文摘 | Elena Marko?i? Boris Kramberger Joost G. van Bennekom Hero Jan Heeres John Vos ?eljko Knez | 2013 | Renewable and Sustainable Energy Reviews2013，，： | 1 |
| 11 | Copper-catalyzed oxidation of alcohols to aldehydes and ketones: an efficient, aerobic alternative显示文摘 | Marko I E Giles P R Tsukazaki M | 1996 | Science1996，274，： | 1 |
| 12 | New scale-invariant nonlinear differential equations for a complex scalar field显示文摘 | Zhdanov R Z Fushchych W I Marko P V | 1996 | Physica D1996，95，2： | 1 |
| 13 | Efficient, aerobic, ruthenium-catalyzed oxidation of alcohols into aldehydes and ketones显示文摘 | Marko I E Gil P R Tsukaza M | 1997 | J Am Chem Soc1997，119，12： | 1 |
| 14 | Copper-cata-lyzed oxidation of alcohols to aldehydes and ketones : anefficient, aerobic alternative 显示文摘 | Marko I E Giles P R Tsukazaki M | 1996 | Science1996，274，5295： | 1 |
| 15 | Efficient,copper-catalyzed, aerobic oxidation of primary alcohols显示文摘 | Marko I E Gautier A Dumeunier R L | 2004 | Angewandte Chemie-Intemational Edition2004，43，12： | 1 |
| 16 | Connective synthesis of polysubstituted tetrahydropyrans by a novel and stereocontrolled metallo-ene/intramolecular Sakurai cyclization sequence显示文摘 | LEROY B MARKO I E | 2002 | J Org Chem2002，67，： | 1 |
| 17 | Asym- metric dihydroxylation via ligand accelerated catalysis 显示文摘 | Jacobsen E N Marko I Mungall W S | 1988 | J Am Chem Soc1988，110，6： | 1 |
| 18 | Highly active and selective platinum (0)-carbene complexes:Efficient,catalytic hydrosilyla tion of functionalised olefms显示文摘 | Marko I E Sterin S Buisine O | | 0，，12： | 1 |
| 19 | HOW MEDICAL STUDENTS IN THEIR PRE-CLINICAL YEAR PERCEIVE PSYCHIATRY AS A CAREER: THE STUDY FROM BELGRADE显示文摘 | Nadja P. Mari? Dragan J. Stojiljkovi? Bojana Mileki? Marko Milanov Darko Stevanovi? Miroslava Ja?ovi?-Ga?i? | 2009 | Psychiatria Danubina2009，，2： | 1 |
| 20 | Efficient, aerobic, ruthenium-catalyzed oxidation of alcohols into aldehydes and ketones显示文摘 | Marko I E Giles P R Tsukazaki M | 1997 | J Am Chem Soc1997，119，12： | 1 |
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