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Pentoxifylline:A first line treatment option for severe alcoholic hepatitis and hepatorenal syndrome?

World Journal of Gastroenterology 2009年第25期15卷 3194-3195页

作者： Stelios F Assimakopoulos Konstantinos c thomopoulos chrisoula Labropoulou-Karatza Department of Internal Medicine University Hospital of Patras Division of Gastroenterology Department of Internal MedicineUniversity Hospital of Patras

Although favourable results of pentoxifylline （PTX） used in treatment of severe alcoholic hepatitis patients with a Maddrey discriminant function score ≥ 32 have been previously reported, it is not currently recommended as a first line treatment for alcoholic hepatitis owing to lack of evidence for its efficacy as compared to the standard treatment with corticosteroids. In a very recent issue of World Journal of Gastroenterology, Dr. De BK and colleagues compared for the first time the two treatment modalities head to head in a randomized controlled study, demonstrating the advantage of PTX over corticosteroids in terms of patients＇ survival and risk-benefit profile. The advantage of PTX over corticosteroids in survival of patients with severe alcoholic hepatitis was found to be related to the prevention of hepatorenal syndrome in their study. This study raises the question of the use of PI-X as a standard treatment for severe alcoholic hepatitis. considering the fact that PTX presented a spectacular efficiency in prevention of hepatorenal syndrome in their study as well as that previous studies have shown that this effect is possibly related to a primary renoprotective action because it is irrelevant of tumor necrosis factor-c~ synthesis inhibition or improved liver function, we tempted to speculate that PXT might be an effective option for prevention and/or treatment of hepatorenal syndrome complicating other forms of advanced liver disease. This attractive theory remains to be elucidated by pressing future studies in view of the lack of effective treatment modalities for hepatorenal syndrome.

关键词： Alcoholic hepatitis Pentoxifylline Hepatorenal syndrome Mortality

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Acute upper gastrointestinal bleeding in operated stomach: Outcome of 105 cases

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World Journal of Gastroenterology 2005年第29期11卷 4570-4573页

作者： Vassiliki N Nikolopoulou Konstantinos c thomopoulos George I Theocharis Vassiliki A Arvaniti constantine E Vagianos Division of Gastroenterology Department of Internal Medicine University Hospital Patras Greece Department of Surgery University Hospital Patras Greece

AIM: To compare the causes and clinical outcome of patients with acute upper gastrointestinal bleeding (AUGB) and a history of gastric surgery to those with AUGB but without a history of gastric surgery in the ***: The causes and clinical outcome were compared between 105 patients with AUGB and a history of gastric surgery, and 608 patients with AUGB but without a history of gastric ***: Patients who underwent gastric surgery in the past were older (mean age: 68.1±11.7 years vs 62.8±17.8 years, P= 0.001), and the most common cause of bleeding was marginal ulcer in 63 patients (60%). No identifiable source of bleeding could be found in 22 patients (20.9%) compared to 42/608 (6.9%) in patients without a history of gastric surgery (P = 0.003). Endoscopic hemostasis was permanently successful in 26 out of 35 patients (74.3%) with peptic ulcers and active bleeding or non-bleeding visible vessel. Nine patients (8.6%) were operated due to continuing or recurrent bleeding,compared to 23/608 (3.8%) in the group of patients without gastric surgery in the past (P= 0.028). Especially in peptic ulcer bleeding patients, emergency surgery was more common in the group of patients with gastric surgery in the past [9/73 (12.3%) vs 19/360 (5.3%), P = 0.025].Moreover surgically treated patients in the past required more blood transfusion (3.3±4.0 vs 1.5±1.7, P = 0.0001) and longer hospitalization time (8.6±4.0 vs 6.9±4.9 d,P = 0.001) than patients without a history of gastric surgery. Mortality was not different between the two groups [4/105 (3.8%) vs 19/608 (3.1%)].cONcLUSION: Upper gastrointestinal bleeding seems to be more severe in surgically treated patients than in non-operated patients.

关键词： Operated stomach Active bleeding Endoscopic hemostasis

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A rare etiology of post-endoscopic retrograde cholangiopancreatography pneumoperitoneum

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World Journal of Gastroenterology 2008年第18期14卷 2917-2919页

作者： Stelios F Assimakopoulos Konstantinos c thomopoulos Sofia Giali christos Triantos Dimitrios Siagris charalambos Gogos Department of Internal Medicine School of Medicine University of Patras Patras 26110 Greece Division of Gastroenterology Department of Internal Medicine School of Medicine University of Patras Patras 26110 Greece

Major complications of endoscopic retrograde cholangiopancreatography (ERcP) include pancreatitis, hemorrhage, cholangitis, and duodenal perforation. The occurrence of free air in the peritoneal cavity post- ERcP is a rare event (ch is usually the result of duodenal or ductal perforation related to therapeutic ERcP with sphincterotomy. We describe for the first time a different aetiology of pneumoperitoneum, in an 84-year-old woman with pancreatic cancer and a large hepatic metastasis, after ERcP with common bile duct stent deployment. Our patient developed, pneumoperitoneum due to air leakage from rupture of intrahepatic bile ducts and Glisson’s capsule in the area of a peripheral large hepatic metastasis. The potential mechanism underlying this complication might be post- ERcP pneumobilia and increased pressure of intrahepatic bile ducts leading to rupture of intrahepatic bile ducts in the liver metastatic mass owing to neoplastic tissue friability. This case indicates the need for close clinical and radiological observation of patients with hepatic masses (primary or metastatic) subjected to ERcP. In such patients, avoidance of excessive air insufflation during ERcP and/or placement of a nasogastric tube for bowel decompression immediately after ERcP might be a reasonable strategy to prevent such unusual complications.

关键词： Endoscopic retrograde cholangiopancreatx ography Pneumoperitoneum complications Pneumobilia Hepatic metastases

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Acute upper gastrointestinal bleeding in octοgenarians:clinical outcome and factors related to mortality

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World Journal of Gastroenterology 2008年第25期14卷 4047-4053页

作者： George J Theocharis Vassiliki Arvaniti Stelios F Assimakopoulos Konstantinos c thomopoulos Vassilis Xourgias Irini Mylonakou Vassiliki N Nikolopoulou Division of Gastroenterology Department of Internal Medicine University Hospital of Patras Department of Gastroenterology "Tzaneio" General Hospital Department of Internal MedicineUniversity Hospital of Patras

AIM: To evaluate the aetiology, clinical outcome and factors related to mortality of acute upper gastrointestinal bleeding (AUGIB) in octogenarians. METHODS: We reviewed the records of all patients over 65 years old who were hospitalised with AUGIB in two hospitals from January 2006 to December of 2006. Patients were divided into two groups: Group A (65-80 years old) and Group B (> 80 years old). RESULTS: Four hundred and sixteen patients over 65 years of age were hospitalized because of AUGIB. Group A included 269 patients and Group B 147 patients. co-morbidity was more common in octogenarians (P = 0.04). The main cause of bleeding was peptic ulcer in both groups. Rebleeding and emergency surgery were uncommon in octogenarians and not different from those in younger patients. In-hospital complications were more common in octogenarians (P = 0.05) and more patients died in the group of octogenarians compared to the younger age group (P = 0.02). Inability to perform endoscopic examination (P = 0.002), presence of high risk for rebleeding stigmata (P = 0.004), urea on admission (P = 0.036), rebleeding (P = 0.004) and presenceof severe co-morbidity (P ce of severe co-morbidity was independently related to mortality (P = 0.032). cONcLUSION: While rebleeding and emergency surgery rates are relatively low in octogenarians with AUGIB, the presence of severe co-morbidity is the main factor of adverse outcome.

关键词： Acute upper gastrointestinal bleeding Octogenarians Elderly co-morbidity Mortality

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Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: Endoscopic findings, clinical management and outcome

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World Journal of Gastroenterology 2005年第9期11卷 1365-1368页

作者： Konstantinos c thomopoulos Konstantinos P Mimidis George J Theocharis Anthie G Gatopoulou Georgios N Kartalis Vassiliki N Nikolopoulou Department of Internal Medicine the First Department of Internal Medicine

AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients. METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin. RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (Pce of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P=0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy. cONcLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.

关键词： AUGIB Anticoagulant therapy Endoscopy

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Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: Effect of bombesin and neurotensin

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World Journal of Gastroenterology 2006年第21期12卷 3410-3415页

作者： Stelios F Assimakopoulos constantine E Vagianos Aristides S charonis Ilias H Alexandris Iris Spiliopoulou Konstantinos c thomopoulos Vassiliki N Nikolopoulou chrisoula D Scopa Department of Internal Medicine School of Medicine University of PatrasPatrasGreece Department of Surgery School of Medicine University of PatrasPatrasGreece Section of Histology center for Basic Research Foundation of Biomedical Research of the Academy of AthensAthensGreece Department of Microbiology School of Medicine University of PatrasPatrasGreece Department of Internal Medicine Division of Gastroenterology School of MedicineUniversity of PatrasPatrasGreece Department of Pathology School of Medicine University of PatrasPatrasGreece

AIM： To investigate the influence of experimental obstructive jaundice and exogenous bombesin （BBS） and neurotensin （NT） administration on the expression of the tight junction （TJ）-protein claudin-4 in intestinal epithelium of rats. METHODS： Forty male Wistar rats were randomly divided into five groups： Ⅰ = controls, Ⅱ = sham operated,Ⅲ = bile duct ligation （BDL）,Ⅳ = BDL＋BBS （30μg/kg per d）, V = BDL＋NT （300μg/kg per d）. At the end of the experiment on d 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of claudin-4 expression in intestinal epithelium. RESULTS： Obstructive jaundice led to intestinal barrier failure demonstrated by significant portal and aortic endotoxemia. claudin-4 expression was significantly increased in the upper third of the villi in jaundiced rats and an upregulation of its lateral distribution was noted. Administration of BBS or NT restored claudin-4 expression to the control state and significantly reduced portal and aortic endotoxemia. cONcLUSION： Experimental obstructive jaundice increases claudin-4 expression in intestinal epithelium,which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT can prevent this alteration and reduce portal and systemic endotoxemia.

关键词： Obstructive jaundice Tight junctions claudin-4 Intestinal permeability Intestinal barrier Regulatory peptides Bombesin Neurotensin

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Unilateral leg edema in a cirrhotic patient with tense ascites

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World Journal of Gastroenterology 2006年第35期12卷 5746-5747页

作者： Stelios F Assimakopoulos Konstantinos c thomopoulos christine Kalogeropoulou Ioannis Maroulis Alexandra Lekkou christos Papakonstantinou constantine E Vagianos charalambos Gogos Department of Internal Mcdicine School of MedieineUniversity of PatrasPatrasgreece Department of Radiology School of MedicineUniversity of Patraspatrasgreece Department of surgery School of MedicineUniversity of palrasPatrasGreece

TO THE EDITOR　　A 61 year old man with cirrhosis and hepatocellular carcinoma developed on the background of chronic hepatitis B was admitted because of acute and gradually intensified right thigh pain and swelling, which, within a few hours, was expanded to his right foot. The patient,due to ascites refractory to diuretics, was almost weekly subjected to large volume paracentesis of ascitic fluid for the last six months; meanwhile he has developed a left inguinal, a right femoral and an umbilical hernia. It should be noted that 48 h before admission, the patient was referred to the emergency room because of dyspnoea and 5 L of ascitic fluid were removed.

关键词： Leg edema Tense ascites cirrhosisAssimakopoulos SF, thomopoulos Kc, Kalogeropoulou

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Effect of bombesin and neurotensin on gut barrier function in partially hepatectomized rats

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World Journal of Gastroenterology 2005年第43期11卷 6757-6764页

作者： Stelios F Assimakopoulos Ilias H Alexandris chrisoula D Scopa Panagiotis G Mylonas Konstantinos c thomopoulos christos D Georgiou Vassiliki N Nikolopoulou constantine E Vagianos Department of Internal Medicine Department of Surgery Department of Pathology Department of Internal edicine Department of Biology

AIM： To investigate the effect of regulatory peptides bombesin （BBS） and neurotensin （NT） on intestinal barrier function in partially hepatectomized rats. METHODS： Ninety male Wistar rats were randomly divided into five groups： Ⅰ （n = 10）： controls, Ⅱ （n = 20）： sham operated, Ⅲ （n = 20）： partial hepatectomy 70% （PHx）, Ⅳ （n = 20）： PHx＋BBS （30 μg/kg/d）, Ⅴ （n = 20）： PHx＋NT （300 μg/kg/d）. Groups IV and V were treated for 8 days before PHx and 48 h post surgery. At the end of the experiment, on day 10, intestinal barrier function was assessed by measuring endotoxin concentrations in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content and microbiological analysis was performed in cecal contents. To estimate intestinal oxidative stress, lipid peroxidation was determined on tissue homogenates from terminal ileum. RESULTS： BBS or NT administration significantly reduced portal and systemic endotoxemia observed 48 h after partial hepatectomy. In hepatectomized rats （group Ⅲ）, a trend towards induction of mucosal atrophy was observed, demonstrated by the reduction of villus density, mucosal thickness, protein content and significant reduction of DNA, while these alterations were reversed by regulatory peptides administration. This trophic effect of BBS and NT was accompanied by induction of mitoses above control levels and a significant reduction of apoptosis in intestinal crypts. Intestinal lipid peroxidation was found significantly lower in PHx group and regulatory peptides exerted an antioxidant action, further decreasing this parameter of oxidative stress. The ：bacterial population of E. coli and aerobic Gram （＋） cocci was increased in cecal content of hepatectomized rats, while this parameter was not affected by the administration of BBS or NT. cONcLUSION： Gut regulatory pep

关键词： Hepatectomy Rats Bombesin Neurotensin Intestinal barrier Apoptosis Oxidative stress

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不同类别降压药降压作用的荟萃分析

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中华高血压杂志 2015年第1期23卷 5-5页

作者：刘莉叶鹏 thomopoulos c Parati G Zanchetti A

多项随机对照试验（randomized controlled trials,RcT）均显示降压作用与所使用的降压药物类别有关,该研究旨在确定是否任何种类降压药均能有效降低心血管预后。方法：纳入55项RcT（195 267例研究对象）进行荟萃分析,采用随机效应模型... 详细信息

多项随机对照试验（randomized controlled trials,RcT）均显示降压作用与所使用的降压药物类别有关,该研究旨在确定是否任何种类降压药均能有效降低心血管预后。方法：纳入55项RcT（195 267例研究对象）进行荟萃分析,采用随机效应模型评估7个致命和非致命性临床预后的发生风险。

关键词：降压药物荟萃分析随机效应模型利尿剂治疗药物治疗随机对照试验心血管事件非致命性钙拮抗剂吲达帕胺

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Intestinal barrier dysfunction in cirrhosis: current concepts in pathophysiology and clinical implications

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World Journal of Hepatology 2015年第17期7卷 2058-2068页

作者： Georgios I Tsiaoussis Stelios F Assimakopoulos Athanassios c Tsamandas christos K Triantos Konstantinos c thomopoulos Department of Gastroenterology and Hepatology University Hospital of Patras Department of Internal Medicine University Hospital of Patras Department of Pathology University Hospital of Patras

The intestinal lumen is a host place for a wide range of microbiota and sets a unique interplay between local immune system, inflammatory cells and intestinal epithelium, forming a physical barrier against microbial invaders and toxins. Bacterial translocation is the migration of viable or nonviable microorganisms or their pathogen-associated molecular patterns, such as lipopolysaccharide, from the gut lumen to the mesenteric lymph nodes, systemic circulation and other normally sterile extraintestinal sites. A series of studies have shown that translocation of bacteria and their products across the intestinal barrier is a commonplace in patients with liver disease. The deterioration of intestinal barrier integrity and the consulting increased intestinal permeability in cirrhotic patients play a pivotal pathophysiological role in the development of severe complications as high rate of infections, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, variceal bleeding, progression of liver injury and hepatocellular carcinoma. Nevertheless, the exact cellular and molecular mechanisms implicated in the phenomenon of microbial translocation in liver cirrhosis have not been fully elucidated yet.

关键词： cirrhosis Intestinal barrier Tight junction Bacterial translocation Intestinal bacterial overgrowth

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