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世界胃肠病学杂志(英文版)
世界胃肠病学杂志(英文版)

潘伯荣

周刊

1007-9327

wjg@wjgnet.com

010-85381901-628

100025

北京市朝阳区东四环中路62号楼远洋国际中心D座903室

世界胃肠病学杂志(英文版)/Journal World Journal of GastroenterologyCSCDCSTPCDSCI
查看更多>>主要报道和刊登国内外、特别是我国消化病学者具有创造性的、有较高学术水平的基础和临床研究论文、研究快报等. 对具有中国特色的研究论文, 如食管癌、胃癌、肝癌、大肠癌、病毒性肝炎、幽门螺杆菌、中医中药、中西医结合和基于作者自己研究工作为主的综述性论文, 将优先发表. 读者对象为基础研究或临床研究的消化专业工作者。
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    Cell sheet technology for regeneration of esophageal mucosa

    Ryo TakagiMasayuki YamatoNobuo KanaiDaisuke Murakami...
    5145-5150页
    查看更多>>摘要:The progress of tissue-engineering technology has realized development of new therapies to treat various disorders by using cultured cells.Cell-and tissue-based therapies have been successfully applied to human patients,and several tissue-engineered products have been approved by the regulatory agencies and are commercially available.In the review article,we describe our experience of development and clinical application of cell sheet-based regenerative medicine.Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been shown to be useful for removal of gastrointestinal neoplasms with less invasiveness compared with open surgery,especially in esophageal surgery.However,postoperative inflammation and stenosis are major complications observed after intensive mucosal resection.Therefore,we have developed novel regenerative medicine to prevent such complications and promote wound healing of esophageal mucosa after EMR or ESD.Transplantable oral mucosal epithelial cell sheets were fabricated from patients' own oral mucosa.Immediately after EMR or ESD,fabricated autologous cell sheets were endoscopically transplanted to the ulcer sites.We performed a preclinical study with a canine model.In human clinical settings,cell culture and cell sheet fabrication were performed in clean rooms according to good manufacturing practice guidelines,and pharmaceutical drugs were used as supplements to culture medium in place of research regents used in animal study.We believe that cell-based regenerative medicine would be useful to improve quality of life of patients after EMR or ESD.

    Irritable bowel syndrome: Diagnosis and pathogenesis

    Magdy El-Salhy
    5151-5163页
    查看更多>>摘要:Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life.It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients.The diagnosis of IBS is based on symptom assessment and the Rome Ⅲ criteria.A combination of the Rome Ⅲ criteria,a physical examination,blood tests,gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis.Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS.The pathogenesis of IBS seems to be multifactorial,with the following factors playing a central role in the pathogenesis of IBS:heritability and genetics,dietary/intestinal microbiota,low-grade inflammation,and disturbances in the neuroendocrine system (NES) of the gut.One hypothesis proposes that the cause of IBS is an altered NES,which would cause abnormal GI motility,secretions and sensation.All of these abnormalities are characteristic of IBS.Alterations in the NES could be the result of one or more of the following:genetic factors,dietary intake,intestinal flora,or low-grade inflammation.Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases.Patients with PI-and IBD-IBS exhibit low-grade mucosal inflammation,as well as abnormalities in the NES of the gut.

    Gastric carcinogenesis

    Ismail GomceliBaris DemirizMesut Tez
    5164-5170页
    查看更多>>摘要:Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths.Despite complete resection of gastric cancer and lymph node dissection,as well as improvements in chemotherapy and radiotherapy,there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis.None of the treatment modalities we have been applying today can influence the overall survival rates:at present,the overall 5-year relative survival rate for gastric cancer is about 28%.Cellular metaplasia due to chronic inflammation,injury and repair are the most documented processes for neoplasia.It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating,sustaining and advancing tumor growth.It is also evident that not all inflammation is tumorigenic.Additional mutations can be acquired,and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype.Intestinalization of gastric units,which is called "intestinal metaplasia";phenotypic antralization of fundic units,which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cell zone are three pathways that have been described for gastric carcinogenesis.Also,an important factor for the development of gastrointestinal cancers is peritumoral stroma.However,the initiating cellular event in gastric metaplasia is still controversial.Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation,and our paper attempts to high-light recent progress in this field of cancer research.

    KRAS mutation testing in metastatic colorectal cancer

    Cong TanXiang Du
    5171-5180页
    查看更多>>摘要:The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers,and KRAS mutational status testing has been highlighted in recent years.The most frequent mutations in this gene,point substitutions in codons 12 and 13,were validated as negative predictors of response to anti-epidermal growth factor receptor antibodies.Therefore,determining the KRAS mutational status of tumor samples has become an essential tool for managing patients with colorectal cancers.Currently,a variety of detection methods have been established to analyze the mutation status in the key regions of the KRAS gene; however,several challenges remain related to standardized and uniform testing,including the selection of tumor samples,tumor sample processing and optimal testing methods.Moreover,new testing strategies,in combination with the mutation analysis of BRAF,PIK3CA and loss of PTEN proposed by many researchers and pathologists,should be promoted.In addition,we recommend that microsatellite instability,a prognostic factor,be added to the abovementioned concomitant analysis.This review provides an overview of KRAS biology and the recent advances in KRAS mutation testing.This review also addresses other aspects of status testing for determining the appropriate treatment and offers insight into the potential drawbacks of mutational testing.

    Effect of double-balloon enteroscopy on pancreas: An experimental porcine model

    Rafael LatorreFederico SoriaOctavio López-AlborsRicardo Sarriá...
    5181-5187页
    查看更多>>摘要:AIM:To evaluate the effect of double-balloon enteroscopy (DBE) on pancreas histology and levels of pancreatic enzymes.METHODS:Conventional upper gastrointestinal endoscopy was performed on five control pigs.Oral DBE was performed with an EN-450T5 enteroscope on 20 pigs.Two experimental groups (10 pigs each) were defined according to DBE duration:90 min for Group 1 and 140 min for Group 2.During oral insertion,the balloons were not inflated in the descending part of the duodenum to avoid the minor duodenal papilla.Serum amylase,lipase and C-reactive protein (CRP) levels were monitored before the procedure and repeated every 30 min until the exploration was finished,as well as 24 h and 7 d after.After the procedure and for a total of 7 d,the pigs were observed twice a day for signs of decreased activity,irritability,vomiting or anorexia.Gross and microscopic examination of the pancreas was performed on day 7.RESULTS:All animals tolerated DBE without clinical manifestations of acute pancreatitis.Experimental groups had higher levels of enzymes than the control group at 24 h.Throughout the exploration,the amylase levels increased significantly above the baseline 24 h after DBE,although the increase was not statistically significant and did not reach 20% of the baseline.An increase in lipase and CRP was observed at 24 h after the procedure,although by day 7,all enzymatic levels had returned to baseline.No differences between Groups 1 and 2 were found for any enzyme and sampiing site during and after the procedure.Similarly,no correlation between insertion depth and enzyme levels was observed.Direct in situ and post-removal inspection of the pancreas did not show any evidence of fluid collection,abscesses or hemorrhage.Histological examination of the pancreas from Groups 1 and 2 revealed the existence of focal areas (0.14-0.26 mm2) of ischemic necrosis in 47.4% of the animals.In the pigs with damaged pancreas,the left lobe (tail) was always affected.However,this only happened in 83.3% of the samples from the right lobe (head) and in 33.3% of the samples from the body of the pancreas.Significant differences were found between the left lobe (tail) and the body for the percentage of affected pancreas.Both the size of the lesions and the percentage of affected pancreas were higher in the left pancreatic lobe (tail).The presence of the lesions was not related to the exploration length.CONCLUSION:The increase in pancreatic enzymes after DBE could be related to focal points of pancreatic ischemic necrosis due to mechanical stress.

    Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B

    Hui ZhangQing-Ya LiZhi-Zhong GuoYan Guan...
    5188-5196页
    查看更多>>摘要:AIM:To investigate whether circulating microRNAs (miRNAs) can serve as molecular markers to predict liver injury resulted from chronic hepatitis B (CHB).METHODS:The profiles of serum miRNA expression were first generated with serum samples collected from 10 patients with CHB and 10 healthy donors (Ctrls) by microarray analysis.The levels of several miRNAs were further quantitated by real-time reverse transcription polymerase chain reaction with serum samples from another 24 CHB patients and 24 Ctrls.Serum samples of 20 patients with nonalcohlic steatohepatitis (NASH) were also included for comparison.The comparison in the levels of miRNAs between groups (CHB,NASH and Ctrl) was analyzed with Mann-Whitney U-test.The correlation between miRNAs and clinical pathoparameters was analyzed using Spearman correlation analysis or canonical correlation analysis.The receiver-operator characteristic (ROC) curves were also generated to determine the specificity and sensitivity of each individual miRNA in distinguishing patients with CHB from Ctrls.RESULTS:miRNA profile analysis showed that 34 miRNAs were differentially expressed between CHB and Ctrl subjects,in which 12 were up-regulated and 22 down-regulated in CHB subject (fold change > 2.0 and P < 0.01).The median levels of miR-122,-572,-575 and-638 were significantly higher (P < 1.00 × 10-5) while miR-744 significantly lower (P < 1.00 × 10-6) in CHB compared with the Ctrl.The levels of miR-122,-572 and-638 were also higher (P < 1.00 × 10-3) while the level of miR-744 lower in CHB (P < 0.05) than in NASH,although the difference between them was not as significant as that between CHB and Ctrl.ROC curve analysis revealed that the levels of miR-122,-572,-575,-638 and-744 in serum were sensitive and specific enough to distinguish CHB,NASH and Ctrl.Multivariate analysis further showed that the levels of these miRNAs were correlated with the liver function parameters.Most significantly,it was the scatter plot of principal component with the levels of these miRNAs,but not the parameters of liver function,which clearly distinguished CHB,NASH and Ctrl subjects.CONCLUSION:Serum levels of miR-122,-572,-575,-638 and-744 are deregulated in patients with CHB or NASH.The levels of these miRNAs may serve as potential biomarkers for liver injury caused by CHB and NASH.

    Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine

    Lei XiangJing-Wang TanLi-Jie HuangLin Jia...
    5197-5204页
    查看更多>>摘要:AIM:To study the effect of H2 gas on liver injury in massive hepatectomy using the Intermittent Pringle maneuver in swine.METHODS:Male Bama pigs (n =14) treated with ketamine hydrochloride and Sumianxin Ⅱ as induction drugs followed by inhalation anesthesia with 2% isoflurane,underwent 70% hepatotectomy with loss of bleeding less than 50 mL,and with hepatic pedicle occlusion for 20 min,were divided into two groups:Hydrogen-group (n =7),the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepatotectomy; Contrast-group (n =7),underwent 70% hepatotectomy without inhalation of hydrogen.Hemodynamic changes and plasma concentrations of alanine aminotransferase (ALT),aspartate aminotransferase (AST),hyaluronic acid (HA),tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),and malondialdehyde (MDA) in liver tissue were measured at pre-operation,post-hepatotectomy (PH) 1 h and 3 h.The apoptosis and proliferating cell nuclear antigen (PCNA) expression in liver remnant were evaluated at PH 3 h.Then we compared the two groups by these marks to evaluate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine.RESULTS:There were no significant differences in body weight,blood loss and removal liver weight between the two groups.There was no significant difference in changes of portal vein pressure between two groups at pre-operation,PH 30 min,but in hydrogen gas treated-group it slightly decrease and lower than its in Contrast-group at PH 3 h,although there were no significant difference (P =0.655).ALT and AST in Hydrogen-group was significantly lower comparing to Contrast-group (P =0.036,P =0.011,vs P =0.032,P =0.013) at PH 1 h and 3 h,although the two groups all increased.The MDA level increased between the two group at PH 1 h and 3 h.In the hydrogen gas treated-group,the MDA level was not significantly significant at pre-operation and significantly low at PH 1 h and 3 h comparing to Contrast-group (P =0.0005,P =0.0004).In Hydrogen-group,the HA level was also significantly low to Contrast-group (P =0.0005,P =0.0005) although the two groups all increased at PH 1 h and 3 h.The expression of cluster of differentiation molecule 31 molecules Hydrogen-group was low to Contrast-group.However,PCNA index (%) was not statistically significant between the two groups (P =0.802).Microphotometric evaluation of apoptotic index (AI) in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-stained tissue after hepatotectomy for 3h,the AI% level in the hydrogen was significantly low to Contrast-group (P =0.012).There were no significant difference between Hydrogen-group and Contrast-group at pre-operation (P =0.653,P =0.423),but after massive hepatotectomy,the TNF-α and IL-6 levels increase,and its in Hydrogen-group was significantly low compared with Contrast-group (P =0.022,P =0.013,vs P =0.016,P =0.012),respectively.Hydrogen-gas inhalation reduce levels of these markers and relieved morphological liver injury and apoptosis.CONCLUSION:H2 gas attenuates markedly ischemia and portal hyperperfusion injury in pigs with massive hepatotectomy,possibly by the reduction of inflammation and oxidative stress,maybe a potential agent for treatment in clinic.

    Repair of bile duct defect with degradable stent and autologous tissue in a porcine model

    Yue-Long LiangYi-Chen YuKun LiuWei-Jia Wang...
    5205-5210页
    查看更多>>摘要:AIM:To introduce and evaluate a new method to repair bile duct defect with a degradable stent and autologous tissues.METHODS:Eight Ba-Ma mini-pigs were used in this study.Experimental models with common bile duct (CBD) defect (0.5-1.0 cm segment of CBD resected) were established and then CBD was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly [sebacic acid-co-(1,3-propanediol)-co-(1,2-propanediol)].In addition,a vascularized greater omentum was placed around the stent and both ends of CBD.Cholangiography via gall bladder was performed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture.Complete blood count was examined pre-and post-operatively to estimate the inflammatory reaction.Liver enzymes and serum bilirubin were examined pre-and post-operatively to evaluate the liver function.Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis.The other three pigs were raised for one year for long-term observation.RESULTS:All the animals underwent surgery successfully.There was no intraoperative mortality and no bile leakage during the observation period.The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation,the difference was not statistically significant (P =0.652).The plasma level of alanine aminotransferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation (P =0.810).Nevertheless,the plasma level of γ-glutamyl transferase was increased after operation in both groups (P =0.004),especially 2 wk after operation.The level of serum total bilirubin after operation was not significantly elevated compared with that before operation (P =0.227),so did the serum direct bilirubin (P =0.759).By cholangiography via gall bladder,we found that the stent maintained its integrity of shape and was still in situ at month 1,and it disappeared completely at month 3.No severe CBD dilation and stricture were observed at both months 1 and 3.No pig died during the 3-mo postoperative observation period.No sign of necrosis,bile duct stricture,bile leakage or abdominal abscess was found at reoperation at month 3 postoperatively.Pigs had neither fragments of stent nor stones formed in the CBD.Collagen deposit was observed in the anastomosis by hematoxylin and eosin (HE) and Masson's trichrome stains.No severe cholestasis was observed in liver parenchyma by HE staining.Intestinal obstruction was found in a pig 4 mo after operation,and no bile leakage,bile duct stricture or biliary obstruction were observed in laparotomy.No sign of bile duct stricture or bile leakage was observed in the other two pigs.CONCLUSION:The novel method for repairing bile duct defect yielded a good short-term effect without postoperative bile duct stricture.However,the long-term effect should be further studied.

    Clinical outcome and predictors of survival after TIPS insertion in patients with liver cirrhosis

    Hauke S HeinzowPhilipp LenzMichael K(o)hlerFrank Reinecke...
    5211-5218页
    查看更多>>摘要:AIM:To determine the clinical outcome and predictors of survival after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation in cirrhotic patients.METHODS:Eighty-one patients with liver cirrhosis and consequential portal hypertension had TIPS implantation (bare metal) for either refractory ascites (RA) (n =27) or variceal bleeding (VB) (n =54).Endpoints for the study were:technical success,stent occlusion and stent stenosis,rebleeding,RA and mortality.Clinical records of patients were collected and analysed.Baseline characteristics [e.g.,age,sex,CHILD score and the model for end-stage liver disease score (MELD score),underlying disease] were retrieved.The Kaplan-Meier method was employed to calculate survival from the time of TIPS implantation and comparisons were made by log rank test.A multivariate analysis of factors influencing survival was carried out using the Cox proportional hazards regression model.Results were expressed as medians and ranges.Comparisons between groups were performed by using the Mann-Whitney U-test and the x2 test as appropriate.RESULTS:No difference could be seen in terms of age,sex,underlying disease or degree of portal pressure gradient (PPG) reduction between the ascites and the bleeding group.The PPG significantly decreased from 23.4 ± 5.3 mmHg (VB) vs 22.1 ± 5.5 mmHg (RA) before TIPS to 11.8 ± 4.0 vs 11.7 ± 4.2 after TIPS implantation (P =0.001 within each group).There was a tendency towards more patients with stage CHILD A in the bleeding group compared to the ascites group (24 vs 6,P =0.052).The median survival for the ascites group was 29 mo compared to > 60 mo for the bleeding group (P =0.009).The number of radiological controis for stent patency was 6.3 for bleeders and 3.8 for ascites patients (P =0.029).Kaplan-Meier calculation indicated that stent occlusion at first control (P =0.027),ascites prior to TIPS implantation (P =0.009),CHILD stage (P =0.013),MELD score (P =0.001) and those patients not having undergone liver transplantation (P =0.024) were significant predictors of survival.In the Cox regression model,stent occlusion (P =0.022),RA (P =0.043),CHILD stage (P =0.015) and MELD score (P =0.004) turned out to be independent prognostic factors of survival.The anticoagulation management (P =0.097),the porto-systemic pressure gradient (P =0.460) and rebleeding episodes (P =0.765) had no significant effect on the overall survival.CONCLUSION:RA,stent occlusion,initial CHILD stage and MELD score are independent predictors of survival in patients with TIPS,speaking for a close follow-up in these circumstances.

    Effectiveness of infliximab after adalimumab failure in Crohn's disease

    María ChaparroMontserrat AndreuManuel Barreiro-de AcostaEsther García-Planella...
    5219-5224页
    查看更多>>摘要:AIM:To evaluate the effectiveness of infliximab as a second-line therapy in Crohn's disease patients after adalimumab failure.METHODS:A historical cohort study in a community-based gastroenterology practice evaluated Crohn's disease patients treated with infliximab (induction plus maintenance) after adalimumab failure.Patients were identified using a large Spanish database (ENEIDA).RESULTS:We included 15 Crohn's disease patients who received infliximab after adalimumab failure.Five patients discontinued adalimumab due to loss of response,3 due to adverse events and 7 due to partial response.After infliximab therapy was started,all patients who had interrupted adalimumab due to loss of efficacy regained response.All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab,but 2 developed adverse events.None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab.CONCLUSION:Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response,however,the benefit of infliximab in primary nonresponders was not established.