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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | Autoimmune hepatitis,one disease with many faces:Etiopathogenetic,clinico-laboratory and histological characteristics显示文摘Autoimmune hepatitis(AIH) is an unresolving progressive liver disease of unknown etiology characterized byhypergammaglobulinemia,autoantibodies detection and interface hepatitis.Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical,laboratory and histological features,AIH diagnosis may be potentially difficult.Therefore,in this in-depth review we summarize the substantial progress on etiopathogenesis,clinical,serological and histological phenotypes of AIH.AIH has a global distribution affecting any age,both sexes and all ethnic groups.Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis.Hypergammaglobulinemia with selective elevation of IgG is found in most cases.Autoimmune attack is perpetuated,possibly via molecular mimicry,and favored by the impaired control of T-regulatory cells.Histology(interface hepatitis,emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic,are still the hallmark for a timely diagnosis.AIH remains a major diagnostic challenge.AIH should be considered in every case in the absence of viral,metabolic,genetic and toxic etiology of chronic or acute hepatitis.Laboratory personnel,hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. | Nikolaos K Gatselis Kalliopi Zachou George K Koukoulis George N Dalekos | 2015 | World Journal of Gastroenterology2015，21，1： | 36 |
| 3 | Pancreatic insulinoma:current issues and trends显示文摘BACKGROUND:Although insulinomas are very rare tumors, they are the most common pancreatic neuroendocrine neoplasms.The incidence in general population is 1-4 per 1 000 000 yearly but the incidence is higher in autopsy studies. The malignancy of insulinomas is difficult to be predicted on the basis of their histological features,and the current WHO classification has been re-evaluated.This review aimed to summarize classical knowledge with current trends in the diagnosis and treatment of insulinomas. DATA SOURCES:A Medline search using terms'insulinoma', 'treatment'and'neuroendocrine tumors'was conducted. Additional references were sourced from key articles. RESULTS:Surgery is the treatment of choice for insulinoma and has an extremely high success rate.Medical treatment is also available but only for patients who are unable or unwilling to undergo surgical treatment.Preoperative localization is necessary for planning the surgical approach.Many methods exist for localization of an insulinoma and can be invasive and non-invasive.The combination of biphasic thin section helical CT and endoscopic ultrasonography(EUS)has an almost 100% sensitivity in localizing insulinomas.Laparoscopic ultrasound is mandatory to localize intraoperatively these tumors.EUS-guided fine needle tattoing is an alternative method of localization in case of lack of laparoscopic ultrasound. CONCLUSION:Laparoscopic resection for benign insulinomas is the procedure of choice,whereas pancreatectomy is reserved for large,potentially malignant tumors. | Dennis Vaidakis John Karoubalis Theodora Pappa George Piaditis George N Zografos | 2010 | Hepatobiliary & Pancreatic Diseases International2010，9，3： | 22 |
| 4 | Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients显示文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases. | Nikolaos K Gatselis Tamás Tornai Zakera Shums Kalliopi Zachou Asterios Saitis Stella Gabeta Roger Albesa Gary L Norman Mária Papp George N Dalekos | 2020 | World Journal of Gastroenterology2020，26，34： | 21 |
| 5 | Multiplex RT-PCR-based detections of CEA, CK20 and EGFR in colorectal cancer patients显示文摘AIM: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting cir-culating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. METHODS: Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival. Median follow-up period was 19 mo (range 8-28 mo). RESULTS: Rates of CEA, CK20 and EGFR detection in CRC patients were 95.5%, 78.4% and 19.3%, respectively. CEA transcripts were detected in 3 healthy volunteer samples (7.5%), whereas all control samples were tested negative for CK20 and EGFR transcripts. The increasing number of positive detections for CEA, CK20 and EGFR transcripts in each blood sample was positively correlated with Astler-Coller disease stage (P< 0.001) and preoperative serum levels of CEA (P=0.029) in CRC patients. Data analysis using Kaplan-Meier estimator documented signif icant differences in the overall survival of the different CRC patient groups as formed according to the increasing number of positivity for CEA, CK20 and EGFR transcripts. CONCLUSION: These data suggest that multiplex RTPCR assay can provide useful information concerning disease stage and overall survival of CRC patients. | Aikaterini Tsouma Chrysanthi Aggeli Panagiotis Lembessis George N Zografos Dimitris P Korkolis Dimitrios Pectasides Maria Skondra Nikolaos Pissimissis Anastasia Tzonou Michael Koutsilieris | 2010 | World Journal of Gastroenterology2010，16，47： | 19 |
| 6 | Choledochal cysts: Similarities and differences between Asian and Western countries显示文摘Choledochal cysts(CCs)are rare bile duct dilatations,intra-and/or extrahepatic,and have higher prevalence in the Asian population compared to Western populations.Most of the current literature on CC disease originates from Asia where these entities are most prevalent.They are thought to arise from an anomalous pancreaticobiliary junction,which are congenital anomalies between pancreatic and bile ducts.Some similarities in presentation between Eastern and Western patients exist such as female predominance,however,contemporary studies suggest that Asian patients may be more symptomatic on presentation.Even though CC disease presents with an increased malignant risk reported to be more than 10%after the second decade of life in Asian patients,this risk may be overstated in Western populations.Despite this difference in cancer risk,management guidelines for all patients with CC are based predominantly on observations reported from Asia where it is recommended that all CCs should be excised out of concern for the presence or development of biliary tract cancer. | George N Baison Morgan M Bonds William S Helton Richard A Kozarek | 2019 | World Journal of Gastroenterology2019，25，26： | 16 |
| 7 | Surgical management of necrotizing pancreatitis:An overview显示文摘Necrotizing pancreatitis is an uncommon yet serious complication of acute pancreatitis with mortality rates reported up to 15%that reach 30%in case of infection.Traditionally open surgical debridement was the only tool in our disposal to manage this serious clinical entity.This approach is however associated with poor outcomes.Management has now shifted away from open surgical debridement to a more conservative management and minimally invasive approaches.Contemporary approach to patients with necrotizing pancreatitis and/or infectious pancreatitis is summarized in the 3Ds:Delay,Drain and Debride.Patients can be managed in the intensive care unit and any intervention should be delayed.Percutaneous drainage can be utilized first and early in the course of the disease,followed by endoscopic drainage or video assisted retroperitoneoscopic drainage if necrosectomy is deemed necessary.Open surgery is now less frequently performed and should be reserved for cases refractory to any other approach.The management of necrotizing pancreatitis therefore requires a multidisciplinary dynamic model of approach rather than being a surgical disease. | George Kokosis Alexander Perez Theodore N Pappas | 2014 | World Journal of Gastroenterology2014，20，43： | 16 |
| 8 | Acute upper gastrointestinal bleeding in octοgenarians:Clinical outcome and factors related to mortality显示文摘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 < 0.0001) were related to mortality. In multivariate analysis, only the presence 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. | George J Theocharis Vassiliki Arvaniti Stelios F Assimakopoulos Konstantinos C Thomopoulos Vassilis Xourgias Irini Mylonakou Vassiliki N Nikolopoulou | 2008 | World Journal of Gastroenterology2008，14，25： | 15 |
| 9 | Cholangiocarcinoma:principles and current trends显示文摘BACKGROUND:Cholangiocarcinoma(CCA)is a lethal cancer of the biliary epithelium,originating from the liver(intrahepatic),at the confluence of the right and left hepatic ducts(hilar)or in the extrahepatic bile ducts.It is a rare malignancy associated with poor prognosis.DATA SOURCES:We searched the PubMed/MEDLINE database for relevant articles published from 1989 to 2008.The search terms used were related to 'cholangiocarcinoma' and its ' treatment'.Although no language restrictions were imposed initially,for the full-text review and final analysis,our resources only permitted the review of articles published in English.This review deals with the treatment of cholangiocarcinoma,the principles and the current trends.RESULTS:The risks and prognostic factors,symptoms and differential diagnosis are thoroughly discussed.In addition,the tools of preoperative diagnosis such as endoscopic retrograde cholangiopancreatography,digital image analysis,fluorescence in situ hybridization and magnetic resonance cholangiopancreatography are reviewed.Moreover,the treatment of CCA is discussed.CONCLUSIONS:The only curative treatment available is surgical management.Unfortunately,many patients present with unresectable tumors,the majority of whom die within a year of diagnosis.Surgical treatment involves major resections of the liver,pancreas and bile duct,with considerable mortality and morbidity.However,in selected cases and where indicated,appropriate management with aggressive surgery may achieve a good outcome with a prolonged survival expectancy. | George N Zografos Athanasios Farfaras Flora Zagouri Dimosthenis Chrysikos Kostas Karaliotas | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，1： | 14 |
| 10 | Acute upper gastrointestinal bleeding in operated stomach: Outcome of 105 cases显示文摘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 past.METHODS: 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 surgery.RESULTS: 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. | Vassiliki N Nikolopoulou Konstantinos C Thomopoulos George I Theocharis Vassiliki A Arvaniti Constantine E Vagianos | 2005 | World Journal of Gastroenterology2005，11，29： | 9 |
| 11 | Prevalence of occult hepatitis B virus infection in haemodialysis patients from central Greece显示文摘AIM:To assess the hepatitis B virus(HBV)-DNA and the prevalence of occult HBV infection in end-stage renal failure(ESRF)patients from Central Greece. METHODS:Sera from 366 ESRF patients attending five out of six dialysis units from Central Greece were investigated for HBV-DNA by real-time polymerase chain reaction.Only serum samples with repeatedly detectable HBV-DNA were considered positive.IgG antibodies to hepatitis C virus(anti-HCV)were tested by a third generation enzyme linked immunosorbent assay(ELISA),while IgG antibodies to hepatitis E virus (anti-HEV)were tested by two commercially available ELISAs.RESULTS:HBV-DNA was detected in 15/366 patient (4.1%)and HBsAg in 20/366(5.5%).The prevalenc of occult HBV infection was 0.9%(3/346 HBsAg negative patients).Occult HBV was not associate with a specific marker of HBV infection or anti-HCV o anti-HEV reactivity.There was no significant differenc in HBV-DNA titres,demographic and biochemica features,between patients with occult HBV infectio and those with HBsAg-positive chronic HBV infection. CONCLUSION:In central Greece,4%of ESRF patient had detectable HBV-DNA,though in this setting,th prevalence of occult HBV seems to be very low(0.9%). | Paraskevi Mina Sarah P Georgiadou Christos Rizos George N Dalekos Eirini I Rigopoulou | 2010 | World Journal of Gastroenterology2010，16，2： | 8 |
| 12 | Primary biliary cirrhosis in HBV and HCV patients:Clinical characteristics and outcome显示文摘AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to September 2009,we retrospectively evaluated the medical records of all HBV(n = 1493) and HCV patients(n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC(8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients,while one third(5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV(56.1 ± 11.2vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics(10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency(87.5% vs33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC. | Eirini I Rigopoulou Kalliopi Zachou Nikolaos K Gatselis Georgia Papadamou George K Koukoulis George N Dalekos | 2013 | World Journal of Hepatology2013，5，10： | 7 |
| 13 | Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing cirrhosis and risk of hepatocellular carcinoma显示文摘AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.RESULTS: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P < 0.001), advanced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P < 0.001), alanine aminotransferase(P < 0.02), γ-glutamyl transpeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P < 0.05), international normalized ratio(P = 0.002) and alpha-fetoprotein levels(P < 0.02), and lower albumin(P < 0.001), and platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U/L vs 9.8(4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis(OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development(P = 0.007) and higher incidence of liver-related death(P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs. | Gary L Norman Nikolaos K Gatselis Zakera Shums Christos Liaskos Dimitrios P Bogdanos George K Koukoulis George N Dalekos | 2015 | World Journal of Hepatology2015，7，14： | 7 |
| 14 | β内酰胺酶和超广谱β内酰胺酶的研究新进展显示文摘本文要点由于不断的突变,能产生β内酰胺酶的细菌数量不断增加,并导致更严重的感染超广突变导致超广谱β内酰胺酶的出现,它们的发生率与类型因地点和时间不同而有变异对那些面临如何治疗产酶菌株引起感染的临床医生而言。 | Joumana N Samaha-Kfoury George F Araj 袁燕 | 2004 | 英国医学杂志中文版2004，7，4： | 7 |
| 15 | Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat显示文摘AIM: To present the characteristics and the course of a series of anti- hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving. | Kalliopi Zachou Alexandros Sarantopoulos Nikolaos K Gatselis Themistoklis Vassiliadis Stella Gabeta Aggelos Stefos Asterios Saitis Panagiota Boura George N Dalekos | 2013 | World Journal of Hepatology2013，5，7： | 6 |
| 16 | Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: Endoscopic findings, clinical management and outcome显示文摘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, 111patients 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 2000-2001with 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 (P<0.05). No identifiable source 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 (NSATDs) (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 NSATDs 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. | Konstantinos C Thomopoulos Konstantinos P Mimidis George J Theocharis Anthie G Gatopoulou Georgios N Kartalis Vassiliki N Nikolopoulou | 2005 | World Journal of Gastroenterology2005，11，9： | 5 |
| 17 | New developments and controversies in iron metabolism and iron chelation therapy显示文摘Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies. | Christina N Kontoghiorghe George J Kontoghiorghes | 2016 | World Journal of Methodology2016，6，1： | 5 |
| 18 | Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients显示文摘AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in firstdegree relatives (FDRs) of Greek PBC patients. METHODS:The presence of antimitochondrial antibodies (AMA) and PBCspecific antinuclear antibodies (ANA) were determined using indirect immunofluores-cence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymp-tomatic for liver-related symptoms FDRs of 44 PBCpatients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepati-tis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The preva-lence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI):12%-28.1% vs 2.5%, 95% CI:0.1%-14.7%, P = 0.01; 18.8%, 95% CI:12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI:1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92, 95% CI:1.25-12.35,P = 0.02). CONCLUSION:In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs. | Theodoros A Zografos Nikolaos Gatselis Kalliopi Zachou Christos Liaskos Stella Gabeta George K Koukoulis George N Dalekos | 2012 | World Journal of Gastroenterology2012，18，34： | 4 |
| 19 | Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial显示文摘 | Somnath Mukherjee Christopher N Hurt John Bridgewater Stephen Falk Sebastian Cummins Harpreet Wasan Tom Crosby Catherine Jephcott Rajarshi Roy Ganesh Radhakrishna Alec McDonald Ruby Ray George Joseph John Staffurth Ross A Abrams Gareth Griffiths Tim Maugh | 2013 | Lancet Oncology2013，，4： | 4 |
| 20 | Terlipressin improves pulmonary pressures in cirrhotic patients with pulmonary hypertension and variceal bleeding or hepatorenal syndrome显示文摘Terlipressin has been shown to improve both pulmonary and systemic hemodynamics in stable cirrhotic patients with pulmonary hypertension,whereas other vasoconstrictors may cause pulmonary pressures to deteriorate We investigated the pulmonary and systemic hemodynamic effects of the first terlipressin dose(2 mg) in 7 cirrhotic patients with PH presenting with variceal bleeding(n=4) or hepatorenal syndrome(n=3).Terlipressin decreased pulmonary vascular resistance(158.8±8.9 vs 186.5±13.9 dynes sec cm-5 ;P=0.003) together with an increase in systemic vascular resistance(2143± 126 vs 1643±126 dynes sec cm-5 ;P<0.001).Terlipressin should be the vasoconstrictor treatment of choice when patients present with variceal bleeding or HRS. | George N Kalambokis Konstantinos Pappas Epameinondas V Tsianos | 2012 | Hepatobiliary & Pancreatic Diseases International2012，11，4： | 4 |
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