Endoscopic ultrasound‐guided pancreatic duct drainage

Endoscopic ultrasound (EUS) has evolved from a purely diagnostic procedure to one with therapeutic capabilities. One of the most challenging therapeutic intervention for endosonographers is EUS‐guided pancreatic drainage. The development of this technique has allowed access and drainage of the main pancreatic duct after failed endoscopic retrograde pancreatography and can avoid invasive procedures such as surgical and percutaneous interventions. This review discusses the indications, technique, challenges, and an algorithmic approach to EUS‐guided pancreatic drainage.     

Cancer biomarker discovery for cholangiocarcinoma: the high‐throughput approaches

Cholangiocarcinoma (CCA) is difficult to diagnose at an early stage and most tumors are detected at late stage where surgery or other therapy is ineffective. Many advanced techniques are applied to diagnose CCA; however, most are expensive and have varying degrees of accuracy. A less invasive and simpler procedure such as serum markers would be of substantial clinical benefit for diagnosis, monitoring, and predicting outcome for CCA patients. Recent advances in “Omics” technologies offer remarkable opportunities for establishment of biomarker‐related to diseases. In this review, the potential biomarkers obtained from proteomics and glycomic studies are evaluated. Several protein markers were discovered from patient specimen, using two dimensional‐differential gel electrophoresis couple with liquid chromatography tandem mass spectrometry (2D‐DIGE/LC‐MS‐MS), matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry (MALDI‐TOF‐MS), surface enhanced laser desorption/ionization (SELDI)‐TOF‐MS and capillary electrophoresis (CE)‐MS, etc. Newly reported CCA‐associated glyco‐biomarkers were identified using lectin‐assisted, monoclonal antibody‐assisted or specific‐target strategies. The combination between carbohydrate binding‐lectin and core protein‐binding mAb significantly increased the values for detection of the glyco‐biomarkers for CCA. Searching for specific and sensitive molecular markers to be used for population screening is worth being evaluated. This could lead to earlier diagnosis and improve outcome. Further investigation of those biomarker functions is also of value in order to better understand the tumor biology and use them as targets for future therapeutic agents.     

Influence of clinically significant portal hypertension on surgical outcomes and survival following hepatectomy for hepatocellular carcinoma: a systematic review and meta‐analysis

Surgical resection is not indicated in patients with portal hypertension in the current guideline of Barcelona Clinic Liver Cancer (BCLC) stage. We report a systematic review and meta‐analysis to determine the impact of clinically significant portal hypertension on survival in patients with hepatocellular carcinoma (HCC) following hepatectomy. Searched data in PubMed, EMBASE, and the Cochrane Library were reviewed and 11 publications were included in the meta‐analysis. The inclusion criteria of clinically significant portal hypertension were esophageal varices and/or thrombocytopenia with splenomegaly. Pooled data were extracted and computed into odds ratios (ORs) for clinical outcome and hazard ratios (HRs) for overall survival. The final pooled data were composed of 2,285 patients. There were 775 patients with clinically significant portal hypertension (PHT group) and 1,510 patients without clinically significant portal hypertension (non‐PHT group). Pooled proportion of mortality was 6.1% (95% confidence interval [CI] 0.032–0.116) in PHT group and 2.8% (95% CI 0.014–0.054) in the non‐PHT group. The pooled proportion of morbidity was 41.7% (95% CI 0.274–0.575) in PHT group and 34.7% (95% CI 0.243–0.467) in non‐PHT group. Pooled data confirmed a significantly higher postoperative mortality in the PHT group, with OR 3.02 (P < 0.001). The PHT group also demonstrated significantly higher occurrence of postoperative complications (OR 1.39, P = 0.008), liver‐related morbidity (OR 3.10, P < 0.00001), and liver failure (OR 2.14, P = 0.0005) compared to the non‐PHT group. According to the overall survival, pooled analysis demonstrated that the PHT group demonstrated poorer survival than the non‐PHT group (HR 1.48, P = 0.007). The analyses support significantly higher rates of postoperative mortality, complications, liver‐related morbidity, liver failure, and poorer overall survival in PHT group compared with the non‐PHT group. Surgical resection should be selected carefully with strict surgical strategy in patients with clinically significant portal hypertension when surgical resection is planned.     

Analysis of new biomarkers for cholangiocarcinoma

Cholangiocarcinoma is one of the most serious diseases in northeast Thailand, where its incidence is reported to be the highest in the world. We tried to develop a new method to detect cholangiocarcinoma in the early stages using serum proteins. We found that after fluorescent labeling of the sugar moiety of serum proteins, a new peak was identified, which might be a promising marker for cholangiocarcinoma.     

Relation of corrected thrombolysis in myocardial infarction frame count and ST‐segment resolution to myocardial tissue perfusion after acute myocardial infarction

Objectives : To evaluate myocardial tissue perfusion by corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and ST‐segment resolution after successful percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Background : Early and sustained potency of infarct‐related artery (IRA) has become the main goal of reperfusion therapy in patients with AMI. However, myocardial tissue perfusion may remain impaired even after the achievement of TIMI grade 3 flow of the epicardial artery without residual stenosis. Methods : CTFC was measured after successful PCI in 63 patients with first AMI. The extent of ST‐segment resolution was recorded 1 hr after reperfusion therapy. The wall motion score index (WMSI) was assessed before and 1 month after PCI. Then we studied the correlation between CTFC, ST‐segment resolution, and WMSI. Results : According to CTFC, the patients with TIMI grade 3 flow after PCI were divided into two groups: CTFC fast group and CTFC slow group. CTFC fast group had higher percentage of complete ST resolution (54.1% vs. 25.0%, P < 0.05) and lower percentage of no ST resolution (2.6% vs. 29.2%, P < 0.05). Improvement of WMSI in the CTFC fast group was significantly greater than that of the CTFC slow group (1.30 ± 0.41 vs. 0.64 ± 0.30, P < 0.05). CTFC had a significant negative correlation with the change in WMSI (r = ?0.75, P < 0.01). Conclusions : Combined with ST‐segment resolution, CTFC could predict risk for patients with successful reperfusion therapy after AMI and provide evidence for additional adjunctive treatment. © 2008 Wiley‐Liss, Inc.     

Molecular aspects of cholangiocarcinoma

Novel targets for therapeutic or chemopreventive approaches against cholangiocarcinoma (CCA) are urgently needed. In this review article, we discuss the molecular aspects of CCA including the role of erbB receptor tyrosine kinases (RTKs), downstream signaling pathways of these erbB RTKs, inflammatory mediators during gallbladder carcinogenesis and bile acids based on our study using a mouse model for human CCA (BK5.erbB2 mice) as well as additional information in the literature.     

Development of a clinical prediction model for an international normalised ratio ≥ 4·5 in hospitalised patients using vitamin K antagonists

Vitamin K antagonists (VKAs) used for the prevention and treatment of thromboembolic disease, increase the risk of bleeding complications. We developed and validated a model to predict the risk of an international normalised ratio (INR) ≥ 4·5 during a hospital stay. Adult patients admitted to a tertiary hospital and treated with VKAs between 2006 and 2010 were analysed. Bleeding risk was operationalised as an INR value ≥4·5. Multivariable logistic regression analysis was used to assess the association between potential predictors and an INR ≥ 4·5 and validated in an independent cohort of patients from the same hospital between 2011 and 2014. We identified 8996 admissions of patients treated with VKAs, of which 1507 (17%) involved an INR ≥ 4·5. The final model included the following predictors: gender, age, concomitant medication and several biochemical parameters. Temporal validation showed a c statistic of 0·71. We developed and validated a clinical prediction model for an INR ≥ 4·5 in VKA‐treated patients admitted to our hospital. The model includes factors that are collected during routine care and are extractable from electronic patient records, enabling easy use of this model to predict an increased bleeding risk in clinical practice.     

Acquired nonsurgical complete atrioventricular block in a child with endocardial cushion defect

Acquired nonsurgical complete atrioventricular block is uncommon in children. We report an 11-year-old asymptomatic girl with endocardial cushion defect who gradually developed progressive conduction abnormality and complete atrioventricular block prior to open heart surgery. To our knowledge, a gradual progressive, nonsurgical, acquired atrioventricular block in endocardial cushion defect has not been described before. This report discusses the possible pathogenesis of acquired nonsurgical complete atrioventricular block in endocardial cushion defect and reviews the literature.     

Tips and tricks of double‐balloon endoscopic retrograde cholangiopancreatography (with video)

Although endoscopic retrograde cholangiopancreatography (ERCP) is technically difficult in patients with altered gastrointestinal tract, double‐balloon endoscopy (DBE) allows endoscopic access to pancreato‐biliary system in such patients. Balloon dilation of biliary stricture and extraction of bile duct stones, placement of biliary stent in patients with Roux‐en‐Y or Billroth‐II reconstruction, using DBE have been reported. However, two major technical parts are required for double‐balloon ERCP (DB‐ERCP). One is insertion of DBE and the other is an ERCP‐related procedure. The important point of DBE insertion is a sure approach to the afferent limb with Roux‐en‐Y reconstruction or Braun anastomosis. Short type DBE with working length 152 cm is beneficial for DB‐ERCP because it is short enough for most biliary accessory devices. In this paper, we introduce our tips and tricks for successful DB‐ERCP.     

粉防己碱对肝星状细胞转化生长因子-β1反应性影响

目的观察低浓度粉防己碱（Tetrandrine）对转化牛长因子-β1（TGF-β1）促进静止期大鼠肝星状细胞（HSCs）活化和维持HSCs活化作用的影响，并探讨该作用与TGF-β1受体后信号通路的关系。方法HSCs原代培养，取静止期（培养3d）和活化HSCs（培养8d），给予TGF-β1（质量浓度5ug／L）和（或）粉防己碱（1．6umol／L）干预，观察HSCs形态变化，分别以RT．PCR和Western blot法检测TGF-β1、Smad7以及α—SMAmRNA和（或）蛋白表达。结果粉防己碱（1．6umol／L）能抑制静止期HSCs胞体伸展，粉防己碱使活化的HSCs膜状伸展的胞体收缩和梭形变，在单纯粉防己碱处理组和混合处理组均可见此现象。在静止期和活化HSCs中，粉防己碱均能抑制TGF-β1．诱导的HSCsd—SMA表达，TGF-β1表达下降，使静止期HSCsSmad7表达上调，但不影响活化HSCs Smad7表达.结论低浓度粉防己碱显著抑制TGF-β1对静止期的HSCs促活化作用和对活化HSCs的活化维持作用，诱导培养活化的HSCs活化逆转，其作用机制在不同活化状态的HSCs中存在差异。     

外源Smad7基因对肝星状细胞Smad7 mRNA及蛋白表达的影响

目的观察外源Smad7基因能否有效转染肝星状细胞及其对Smad7 mRNA和蛋白表达的影响。方法构建鼠Smad7真核表达重组质粒，脂质体介导转染HSC—T6细胞，以RT—PCR和Western blot检测正常对照组、空质粒组及转染组中Smad7表达情况。结果Smad7真核表达质粒构建成功；外源Smad7体外转染肝星状细胞后，Smad7 mRNA和蛋白水平均显著上调，Smad7转染组与正常对照、空质粒组比较：Smad7 mRNA表达显著增加（P=0．009，0．011），蛋白水平显著上调（P=0．020，0．026），正常对照组、空质粒组Smad7 mRNA和蛋白水平表达差异无统计学意义（P=0．944，0．644）。结论Smad7真核表达质粒构建成功，外源Smad7基因可有效转染肝星状细胞，并显著上调Smad7 mRNA和蛋白水平。     

大鼠Smad7真核表达质粒的构建及在肝星状细胞中的表达

目的:构建并鉴定大鼠Smad7真核表达质粒,观察外源Smad7对肝星状细胞HSC-T6的转染.并进一步研究其对TGF-β1及Ⅰ、Ⅲ型胶原mRNA达水平的影响.方法:采用基因重组技术将Smad7 cDNA插入真核表达载体pcDNA3.1( ),构建大鼠Smad7真核表达质粒.脂质体介导转染HSC-T6细胞,分为正常对照组、空质粒组及转染组,G418筛选,挑取阳性细胞,运用Western blot检测Smad7蛋白表达情况,RT-PCR检测Smad7、TGF-β1及Ⅰ、Ⅲ型胶原mRNA的表达水平.结果:酶切和测序结果证实Smad7真核表达质粒构建成功.Smad7转染组与正常对照、空质粒组比较,Smad7 mRNA表达显著增加(1.053±0.009 VS 0.984±0.054,0.986±0.044,P<0.01或0.05),蛋白水平显著上调(0.083±0.02 VS0.058±0.050,0.056±0.064,均p<0.05:Smad7转染组TGF-β1、Ⅰ型胶原mRNA表达降低(0.961±0.013 VS 1.039±0.013,1.032±0.037;0.592±0.096 VS 0.767±0.085.0.770±0.090,均P<0.01);Ⅲ型胶原mRNA表达差异无统计学意义.正常对照、空质粒组Smad7 mRNA和蛋白水平、TGF-β1、Ⅰ、Ⅲ型胶原mRNAA达差异无统计学意义.结论:smad7可能参与TGF-β/smad信号转导,在一定程度上具有抗纤维化的生物学活性.