Gastroenterology Research and Practice The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Effects of Two Common Polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on Gastric Cancer Susceptibility Thu, 23 Apr 2015 14:19:08 +0000 Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk. Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI). Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model. Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect. Qing Ni, Anlai Ji, Junfeng Yin, Xiangjun Wang, and Xinnong Liu Copyright © 2015 Qing Ni et al. All rights reserved. TLR3 Plays Significant Roles against HBV-Associated HCC Thu, 23 Apr 2015 13:43:59 +0000 Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). The role of TLR3 in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infections is not well understood. To investigate the ability of TLR3 in regulating HBV replication in HCC, 80 cases of human HCC were collected and their tissue microarray was made. In HCC cells, the expression and location of TLR3, hepatitis-associated virus, and interstitial immunoreactive cells were assayed with immunohistochemical staining. The apoptosis of tumor cells was also detected by TUNEL stain. Correlations between TLR3 expression and HBV infection, interstitial immunoreactive cells, and cells apoptosis in HCC were investigated. In addition, we explored whether TLR3 agonist dsRNA can inhibit HepG2.2.15 cells secreting HBV. We found that the cytoplasmic expression of TLR3 in HCC is positively related to HBsAg infection and HCC with cirrhosis and promotes interstitial immunoreactive cells infiltration and cancer cells apoptosis. In HepG2.2.15 cells, dsRNA inhibited the secretion of HBV and induced apoptosis. These results indicate that TLR3 signaling activity may be involved in immune responses against HBV in HCC. Xiao-lan Chen, Yu-yin Xu, Li Chen, Gui-lan Wang, and Yin Shen Copyright © 2015 Xiao-lan Chen et al. All rights reserved. KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer? Thu, 23 Apr 2015 13:26:49 +0000 KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR) monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE) samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27%) and specificity (64%) in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100%) and specificity (100%) in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer. Nicolas Piton, Francesco Borrini, Antonio Bolognese, Aude Lamy, and Jean-Christophe Sabourin Copyright © 2015 Nicolas Piton et al. All rights reserved. Hepatorenal Syndrome: Outcome of Response to Therapy and Predictors of Survival Thu, 23 Apr 2015 13:20:27 +0000 Aim. Treatment of hepatorenal syndrome (HRS) in patients with liver cirrhosis is still challenging and characterized by a very high mortality. This study aimed to delineate treatment patterns and clinical outcomes of patients with HRS intravenously treated with terlipressin. Methods. In this retrospective single-center cohort study, 119 patients (median [IQR]; 56.50 [50.75–63.00] years of age) with HRS were included. All patients were treated with terlipressin and human albumin intravenously. Those with response to treatment () were compared to the patient cohort without improvement (). Patient characteristics and clinical parameters (Child stage, ascites, hepatic encephalopathy, HRS type I/II, and initial MELD score) were retrieved. Univariate analysis of factors influencing the success of terlipressin therapy and Cox regression analysis of factors influencing survival was carried out. Results. One-month survival was significantly longer in the group of responders (). Cox regression analysis identified age [Hazard ratio, 95% confidence interval (CI); 1.05, 1.01–1.09, resp.], alcohol abuse [HR 3.05, 95% CI 1.11–8.38], duration of treatment [HR 0.92, 95% CI 0.88–0.96], and MELD score [HR 1.08, 95% CI 1.02–1.14] to be independent predictors of survival. Conclusions. Survival of HRS patients after treatment depends on age, etiology of liver disease, and the duration of treatment. Jan Heidemann, Christoph Bartels, Christoph Berssenbrügge, Hartmut Schmidt, and Tobias Meister Copyright © 2015 Jan Heidemann et al. All rights reserved. Inhibitory Effect of Endostar on Specific Angiogenesis Induced by Human Hepatocellular Carcinoma Thu, 23 Apr 2015 13:05:01 +0000 To investigate the effect of endostar on specific angiogenesis induced by human hepatocellular carcinoma, this research systematically elucidated the inhibitory effect on HepG2-induced angiogenesis by endostar from 50 ng/mL to 50000 ng/mL. We employed fluorescence quantitative Boyden chamber analysis, wound-healing assay, flow cytometry examination using a coculture system, quantitative analysis of tube formation, and in vivo Matrigel plug assay induced by HCC conditioned media (HCM) and HepG2 compared with normal hepatocyte conditioned media (NCM) and L02. Then, we found that endostar as a tumor angiogenesis inhibitor could potently inhibit human umbilical vein endothelial cell (HUVEC) migration in response to HCM after four- to six-hour action, inhibit HCM-induced HUVEC migration to the lesion part in a dose-dependent manner between 50 ng/mL and 5000 ng/mL at 24 hours, and reduce HUVEC proliferation in a dose-dependent fashion. Endostar inhibited HepG2-induced tube formation of HUVECs which peaked at 50 ng/mL. In vivo Matrigel plug formation was also significantly reduced by endostar in HepG2 inducing system rather than in L02 inducing system. It could be concluded that, at cell level, endostar inhibited the angiogenesis-related biological behaviors of HUVEC in response to HCC, including migration, adhesion proliferation, and tube formation. At animal level, endostar inhibited the angiogenesis in response to HCC in Matrigel matrix. Qing Ye, Shukui Qin, Yanhong Liu, Jundong Feng, Qiong Wu, Wenshu Qu, and Xiaojin Yin Copyright © 2015 Qing Ye et al. All rights reserved. Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug Thu, 23 Apr 2015 12:42:45 +0000 Implantation of self-expanding metal stents (SEMS) is palliation for patients suffering from inoperable malignant obstructions associated with biliary and pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed because SEMS are susceptible to occlusion by tumor in-growth. We reported recently that paclitaxel-eluting SEMS provide enhanced local drug delivery in an animal model. However, little is known about the molecular mechanisms by which paclitaxel-eluting stents attenuate tumor growth. We investigated the signal transduction pathways underlying the antiproliferative effects of a paclitaxel-eluting membrane (PEM) implanted in pancreatic/cholangiocarcinoma tumor bearing nude mice. Molecular and cellular alterations were analyzed in the PEM-implanted pancreatic/cholangiocarcinoma xenograft tumors by Western blot, immunoprecipitation, and immunofluorescence. The quantities of paclitaxel released into the tumor and plasma were determined by liquid chromatography-tandem mass spectroscopy. Paclitaxel from the PEM and its diffusion into the tumor inhibited angiogenesis, which involved suppression of mammalian target of rapamycin (mTOR) through regulation of hypoxia inducible factor (HIF-1) and increased apoptosis. Moreover, implantation of the PEM inhibited tumor-stromal interaction-related expression of proteins such as CD44, SPARC, matrix metalloproteinase-2, and vimentin. Local delivery of paclitaxel from a PEM inhibited growth of pancreatic/cholangiocarcinoma tumors in nude mice by suppressing angiogenesis via the mTOR and inducing apoptosis signal pathway. Sookhee Bang, Sung Ill Jang, Su Yeon Lee, Yi-Yong Baek, Jieun Yun, Soo Jin Oh, Chang Woo Lee, Eun Ae Jo, Kun Na, Sugeun Yang, Don Haeng Lee, and Dong Ki Lee Copyright © 2015 Sookhee Bang et al. All rights reserved. Expression of Helicobacter pylori hspA Gene in Lactococcus lactis NICE System and Experimental Study on Its Immunoreactivity Wed, 22 Apr 2015 13:54:30 +0000 Aim. The aim of this study was to develop an oral Lactococcus lactis (L. lactis) vaccine against Helicobacter pylori (H. pylori). Methods. After L. lactis NZ3900/pNZ8110-hspA was constructed, growth curves were plotted to study whether the growth of recombinant L. lactis was affected after hspA was cloned into L. lactis and whether the growth of empty bacteria, empty plasmid bacteria, and recombinant L. lactis was affected by different concentrations of Nisin; SDS-PAGE and Western blot were adopted, respectively, to detect the HspA expressed by recombinant L. lactis and its immunoreactivity. Results. There was no effect observed from the growth curve after exogenous gene hspA was cloned into L. lactis NZ3900; different concentrations of Nisin did not affect the growth of NZ3900 and NZ3900/pNZ8110, while different concentrations of Nisin inhibited the growth of NZ3900/pNZ8110-hspA except 10 ng/mL Nisin. No HspA strip was observed from SDS-PAGE. Western blot analysis showed that HspA expressed by recombinant bacteria had favorable immunoreactivity. Conclusion. The growth of recombinant L. lactis was suppressed even though a small amount of HspA had been induced to express. Therefore recombinant L. lactis only express HspA which was not suitable to be oral vaccine against Helicobacter pylori. Xiao-Juan Zhang, Shu-Ying Feng, Zhi-Tao Li, and Yan-Ming Feng Copyright © 2015 Xiao-Juan Zhang et al. All rights reserved. D-Lactic Acidosis: An Underrecognized Complication of Short Bowel Syndrome Wed, 22 Apr 2015 07:46:36 +0000 D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs primarily in individuals who have a history of short bowel syndrome. The unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic acid among other organic acids. The acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, hence giving rise to a vicious cycle. D-lactic acid accumulation in the blood can cause neurologic symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a combination of clinical and laboratory data including special assays for D-lactate. Treatment includes correcting the acidosis and decreasing substrate for D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to clear colonic flora. Although newer techniques for diagnosis and treatment are being developed, clinical diagnosis still holds paramount importance, as there can be many confounders in the diagnosis as will be discussed subsequently. N. Gurukripa Kowlgi and Lovely Chhabra Copyright © 2015 N. Gurukripa Kowlgi and Lovely Chhabra. All rights reserved. Feasibility and Safety of Overtubes for PEG-Tube Placement in Patients with Head and Neck Cancer Tue, 21 Apr 2015 13:13:51 +0000 Background. Percutaneous endoscopic gastrostomy (PEG) placement using the “pull” technique is commonly utilized for providing nutritional support in head and neck cancer (HNC) patients, but it may be complicated by peristomal metastasis in up to 3% of patients. Overtube-assisted PEG placement might reduce this risk. However, this technique has not been systemically studied for this purpose to date. Methods. Retrospective analysis of consecutive patients with HNC who underwent overtube-assisted PEG placement at Westmead Hospital, Australia, between June 2011 and December 2013. Data were extracted from patients’ endoscopy reports and case notes. We present our technique for PEG insertion and discuss the feasibility and safety of this method. Results. In all 53 patients studied, the PEG tubes were successfully placed using 25 cm long flexible overtubes, in 89% prophylactically (before commencing curative chemoradiotherapy), and in 11% reactively (for treatment of tumor related dysphagia or weight loss). During a median follow-up period of 16 months, 3 (5.7%) patients developed peristomal infection and 3 others developed self-limiting peristomal pain. There were no cases of overtube-related adverse events or overt cutaneous metastases observed. Conclusions. Overtube-assisted PEG placement in patients with HNC is a feasible, simple, and safe technique and might be effective for preventing cutaneous metastasis. Crispin O. Musumba, Julia Hsu, Golo Ahlenstiel, Nicholas J. Tutticci, Kavinderjit S. Nanda, David van der Poorten, Eric Y. Lee, and Vu Kwan Copyright © 2015 Crispin O. Musumba et al. All rights reserved. Epigenetic-Mediated Downregulation of μ-Protocadherin in Colorectal Tumours Mon, 20 Apr 2015 12:30:13 +0000 Carcinogenesis involves altered cellular interaction and tissue morphology that partly arise from aberrant expression of cadherins. Mucin-like protocadherin is implicated in intercellular adhesion and its expression was found decreased in colorectal cancer (CRC). This study has compared MUPCDH (CDHR5) expression in three key types of colorectal tissue samples, for normal mucosa, adenoma, and carcinoma. A gradual decrease of mRNA levels and protein expression was observed in progressive stages of colorectal carcinogenesis which are consistent with reports of increasing MUPCDH 5′ promoter region DNA methylation. High MUPCDH methylation was also observed in HCT116 and SW480 CRC cell lines that revealed low gene expression levels compared to COLO205 and HT29 cell lines which lack DNA methylation at the MUPCDH locus. Furthermore, HCT116 and SW480 showed lower levels of RNA polymerase II and histone H3 lysine 4 trimethylation (H3K4me3) as well as higher levels of H3K27 trimethylation at the MUPCDH promoter. MUPCDH expression was however restored in HCT116 and SW480 cells in the presence of 5-Aza-2′-deoxycytidine (DNA methyltransferase inhibitor). Results indicate that μ-protocadherin downregulation occurs during early stages of tumourigenesis and progression into the adenoma-carcinoma sequence. Epigenetic mechanisms are involved in this silencing. Bujko Mateusz, Kober Paulina, Statkiewicz Małgorzata, Mikula Michal, Ligaj Marcin, Zwierzchowski Lech, Ostrowski Jerzy, and Siedlecki Janusz Aleksander Copyright © 2015 Bujko Mateusz et al. All rights reserved. MicroRNAs in Pancreatic Cancer: Involvement in Carcinogenesis and Potential Use for Diagnosis and Prognosis Sun, 19 Apr 2015 12:25:38 +0000 Pancreatic cancer is one of the most fatal malignancies with increasing incidence and high mortality. Possibilities for early diagnosis are limited and there is currently no efficient therapy. Molecular markers that have been introduced into diagnosis and treatment of other solid tumors remain unreciprocated in this disease. Recent discoveries have shown that certain microRNAs (miRNAs) take part in fundamental molecular processes associated with pancreatic cancer initiation and progression including cell cycle, DNA repair, apoptosis, invasivity, and metastasis. The mechanism involves both positive and negative regulation of expression of protooncogenes and tumor suppressor genes. Various miRNAs are expressed at different levels among normal pancreatic tissue, chronic pancreatitis, and pancreatic cancer and may therefore serve as a tool to differentiate chronic pancreatitis from early stages of cancer. Other miRNAs can indicate the probable course of the disease or determine the survival prognosis. In addition, there is a growing interest directed at the understanding of miRNA-induced molecular mechanisms. The possibility of intervention in the molecular mechanisms of miRNAs regulation could begin a new generation of pancreatic cancer therapies. This review summarizes the recent reports describing functions of miRNAs in cellular processes underlying pancreatic cancerogenesis and their utility in diagnosis, survival prognosis, and therapy. Tereza Halkova, Romana Cuperkova, Marek Minarik, and Lucie Benesova Copyright © 2015 Tereza Halkova et al. All rights reserved. Peripheral Signals Mediate the Beneficial Effects of Gastric Surgery in Obesity Wed, 15 Apr 2015 06:35:48 +0000 Obesity is nowadays a public health problem both in the industrialized world and developing countries. The different treatments to fight against obesity are not very successful with the exception of gastric surgery. The mechanism behind the achievement of this procedure remains unclear although the modifications in the pattern of gastrointestinal hormones production appear to be responsible for the beneficial effect. The gastrointestinal tract has emerged in the last time as an endocrine organ in charge of response to the different stimulus related to nutritional status by the modulation of more than 30 signals acting at central level to modulate food intake and body weight. The production of some of these gastric derived signals has been proved to be altered in obesity (ghrelin, CCK, and GLP-1). In fact, bariatric surgery modifies the production of both gastrointestinal and adipose tissue peripheral signals beyond the gut microbiota composition. Through this paper the main peripheral signals altered in obesity will be reviewed together with their modifications after bariatric surgery. Silvia Barja-Fernández, Cintia Folgueira, Cecilia Castelao, Rosaura Leis, Felipe F. Casanueva, and Luisa M. Seoane Copyright © 2015 Silvia Barja-Fernández et al. All rights reserved. Repeat Upper Gastrointestinal Endoscopy in Patients with Functional Dyspepsia: Yield, Findings, and Predictors of Positive Findings Sun, 12 Apr 2015 08:35:39 +0000 Background. No guideline on repeat esophagogastroduodenoscopy (EGD) in functional dyspepsia (FD) exists. This study aimed to define yield, findings, and predictors of positive findings on repeat EGD in FD. Methods. FD patients who underwent at least 2 EGDs during October 2005 to November 2011 were enrolled and reviewed. Yield and findings were analyzed and univariate and multivariate analyses were performed to identify predictors of positive repeat EGD. Results. The median time to repeat EGD was 34 months. Among 146 patients, 115 patients (79%) had negative and 31 (21%) had positive repeat EGD, including erosive gastritis (13.0%), peptic ulcer (7.5%), reflux esophagitis (1.4%), and Barrett’s esophagus (0.7%). Four independent predictors of positive repeat EGD were smoking (HR 3.88, 95% CI 1.31–11.51, ), hypertension (HR 2.96, 95% CI 1.38–6.36, ), history of malignancies (HR 3.65, 95% CI 1.16–11.46, ), and antiplatelets or NSAIDs used within 4 weeks (HR 4.10, 95% CI 1.13–14.90, ), while alarm features or failure to treatment did not predict positive repeat EGD.  Conclusion. Yield of repeat EGD in FD was substantially low, all findings were acid-related disorders, and there was no malignancy. Smoking, hypertension, history of malignancies, and antiplatelets/NSAIDs use associated with positive repeat EGD. Supot Pongprasobchai, Natta Asanaleykha, and Pongchirat Tantayakom Copyright © 2015 Supot Pongprasobchai et al. All rights reserved. Are Histrionic Personality Traits Associated with Irritability during Conscious Sedation Endoscopy? Sun, 12 Apr 2015 08:02:16 +0000 Aim. We aimed to evaluate whether histrionic personality traits are associated with irritability during conscious sedation endoscopy (CSE). Materials and Methods. A prospective cross-sectional study was planned. Irritability during CSE was classified into five grades: 0, no response; I, minimal movement; II, moderate movement; III, severe movement; IV, fighting against procedure. Patients in grades III and IV were defined as the irritable group. Participants were required to complete questionnaire sheet assessing the extent of histrionic personality traits, extraversion-introversion, and current psychological status. The present authors also collected basic sociodemographic data including alcohol use history. Results. A total of 32 irritable patients and 32 stable patients were analyzed. The histrionic personality trait score of the irritable group was higher than that of the stable group (9.5 ± 3.1 versus 6.9 ± 2.9; P = 0.001), as was the anxiety score (52.8 ± 8.6 versus 46.1 ± 9.6; P = 0.004). Heavy alcohol use was more frequently observed in the irritable group (65.6% versus 28.1%; P = 0.003). In multivariate analysis, all these three factors were independently correlated with irritability during CSE. Conclusion. This study revealed that histrionic personality traits, anxiety, and heavy alcohol use can affect irritability during CSE. Sang Shin Lee, Hyung Hun Kim, and Hyo Jung Park Copyright © 2015 Sang Shin Lee et al. All rights reserved. The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis Thu, 09 Apr 2015 11:45:26 +0000 A novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and tested in vitro (LPS-activated macrophages) for its cytotoxicity and anti-inflammatory activity and in vivo (DNBS induced rat model) for its potential to ameliorate induced colitis. Specifically, the competence of P-5 to reduce TNFα, IL-6, INFγ, MCP-1, IL-1α, MIP-1α, and RANTES in LPS-activated macrophages was measured. Experimental colitis was quantified in the rat model, macroscopically and by measuring the activity of tissue MPO and iNOS and levels of TNFα and IL-1β. It was found that P-5 decreased the levels of TNFα and the tested proinflammatory cytokines and chemokines in LPS-activated macrophages. In the colitis-induced rat model, P-5 was effective locally in reducing mucosal inflammation. This activity was equal to the activity of local treatment with 5-aminosalicylic acid. It is speculated that P-5 may be used for the local treatment of IBD (e.g., with the aid of colon-specific drug platforms). Its mode of action involves inhibition of the phosphorylation of MAPK ERK but not of p38 and had no effect on IκBα. Dorit Moradov, Helena Shifrin, Efrat Harel, Mirela Nadler-Milbauer, Marta Weinstock, Morris Srebnik, and Abraham Rubinstein Copyright © 2015 Dorit Moradov et al. All rights reserved. The Efficacy of Endoscopic Papillary Balloon Dilation for Patients with Acute Biliary Pancreatitis Thu, 09 Apr 2015 08:50:07 +0000 Background. No study investigated the efficacy and safety of endoscopic papillary balloon dilation (EPBD) for the treatment of acute biliary pancreatitis (ABP). Method. We retrospectively reviewed the effects of EPBD on patients with ABP from February 2003 to December 2012. The general data, findings of image studies, details of the procedure, and outcomes after EPBD were analyzed. Result. Total 183 patients (male/female: 110/73) were enrolled. The mean age was 65.9 years. Among them, 155 patients had mild pancreatitis. The meantime from admission to EPBD was 3.3 days. Cholangiogram revealed filling defects inside the common bile duct (CBD) in 149 patients. The mean dilating balloon size was 10.5 mm and mean duration of the dilating procedure was 4.3 minutes. Overall, 124 patients had gross stones retrieved from CBD. Four (2.2%) adverse events and 2 (1.1%) intraprocedure bleeding incidents but no procedure-related mortality were noted. Bilirubin and amylase levels significantly decreased after EPBD. On average, patients resumed oral intake within 1.4 days. The clinical parameters and outcomes were similar in patients with different severity of pancreatitis. Conclusion. EPBD can be effective and safe for the treatment of ABP, even in patients presenting with severe disease. Wei-Chih Sun, Hoi-Hung Chan, Kwok-Hung Lai, Tzung-Jiun Tsai, Huey-Shyan Lin, Kung-Hung Lin, Kai-Ming Wang, Sung-Shuo Kao, Po-Hung Chiang, Jin-Shiung Cheng, Ping-I Hsu, Wei-Lun Tsai, Wen-Chi Chen, Yun-Da Li, and E-Ming Wang Copyright © 2015 Wei-Chih Sun et al. All rights reserved. Serrated Polyps and Their Alternative Pathway to the Colorectal Cancer: A Systematic Review Tue, 07 Apr 2015 16:31:52 +0000 Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world. For a long time, only one pathway of colorectal carcinogenesis was known. In recent years, a new “alternative” pathway through serrated adenoma was described. Recent meta-analysis estimated these cancers as about 10% to 30% of all CRCs. Serrated polyps are the second most popular groups of polyps (after conventional adenomas) found during colonoscopy. Serrated polyps of the colon are clinically and molecularly diverse changes that have common feature as crypt luminal morphology characterized by glandular serration. Evidence suggests that subtypes of serrated polyps, particularly TSA and SSA/P, can lead to adenocarcinoma through the serrated pathway. Moreover, the data indicate that the SSA/P are the precursors of colorectal carcinoma by MSI and may be subject to rapid progression to malignancy. An important step to reduce the incidence of CRC initiated by the serrated pathway is to improve the detection of serrated polyps and to ensure their complete removal during endoscopy. Understanding of the so-called serrated carcinogenesis pathway is an important step forward in expanding possibilities in the prevention of CRC. Łukasz Szylberg, Marlena Janiczek, Aneta Popiel, and Andrzej Marszałek Copyright © 2015 Łukasz Szylberg et al. All rights reserved. Fast MR Imaging of the Paediatric Abdomen with CAIPIRINHA-Accelerated T1w 3D FLASH and with High-Resolution T2w HASTE: A Study on Image Quality Tue, 07 Apr 2015 08:13:22 +0000 The aim of this study was to explore the applicability of fast MR techniques to routine paediatric abdominopelvic MRI at 1.5 Tesla. “Controlled Aliasing in Parallel Imaging Results in Higher Acceleration-” (CAIPIRINHA-) accelerated contrast-enhanced-T1w 3D FLASH imaging was compared to standard T1w 2D FLASH imaging with breath-holding in 40 paediatric patients and to respiratory-triggered T1w TSE imaging in 10 sedated young children. In 20 nonsedated patients, we compared T2w TIRM to fat-saturated T2w HASTE imaging. Two observers performed an independent and blinded assessment of overall image quality. Acquisition time was reduced by the factor of 15 with CAIPIRINHA-accelerated T1w FLASH and by 7 with T2w HASTE. With CAIPIRINHA and with HASTE, there were significantly less motion artefacts in nonsedated patients. In sedated patients, respiratory-triggered T1w imaging in general showed better image quality. However, satisfactory image quality was achieved with CAIPIRINHA in two sedated patients where respiratory triggering failed. In summary, fast scanning with CAIPIRINHA and HASTE presents a reliable high quality alternative to standard sequences in paediatric abdominal MRI. Paediatric patients, in particular, benefit greatly from fast image acquisition with less breath-hold cycles or shorter sedation. Mengxia Li, Beate Winkler, Thomas Pabst, Thorsten Bley, Herbert Köstler, and Henning Neubauer Copyright © 2015 Mengxia Li et al. All rights reserved. Hybrid Push-Pull Endoscopic and Laparoscopic Full Thickness Resection for the Minimally Invasive Management of Gastrointestinal Stromal Tumors: A Pilot Clinical Study Mon, 06 Apr 2015 13:56:16 +0000 Background. Gastric gastrointestinal stromal tumors (GISTs) that are predominantly endophytic or in anatomically complex locations pose a challenge for laparoscopic wedge resection; however, endoscopic resection can be associated with a positive deep margin given the fourth-layer origin of the tumors. Methods. Patients at two tertiary care academic medical centers with gastric GISTs in difficult anatomic locations or with a predominant endophytic component were considered for enrollment. Preoperative esophagogastroduodenoscopy (EGD), endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA), and cross-sectional imaging were performed. Eligible patients were offered and consented for hybrid and standard management. Results. Over ten months, four patients in two institutions with anatomically complex or endophytic GISTs underwent successful, uncomplicated push-pull hybrid procedures. GIST was confirmed in all resection specimens. Conclusion. In a highly selected population, the hybrid push-pull approach was safe and effective in the removal of complex gastric GISTs. Endoscopic resection alone was associated with a positive deep margin, which the push-pull technique manages with a laparoscopic, full thickness, R0 resection. This novel, minimally invasive, hybrid laparoscopic and endoscopic push-pull technique is a safe and feasible alternative in the management of select GISTs that are not amenable to standard laparoscopic resection. Field F. Willingham, Paul Reynolds, Melinda Lewis, Andrew Ross, Shishir K. Maithel, and Flavio G. Rocha Copyright © 2015 Field F. Willingham et al. All rights reserved. Nuclear Factor Kappa B, Matrix Metalloproteinase-1, p53, and Ki-67 Expressions in the Primary Tumors and the Lymph Node Metastases of Colorectal Cancer Cases Mon, 06 Apr 2015 08:15:08 +0000 Colorectal cancer (CRC) is the third most frequent malignancy. Many factors such as NF-κB, matrix metalloproteinase-1 (MMP-1), p53, and Ki-67 are likely to be involved in its development and progression. Lymph node metastases indicate increased tumor burden and tumor cell heterogeneity and affect both the treatment strategies and the prognosis. In this study, expressions of NF-κB, MMP-1, p53, and Ki-67 were between the primary tumors and lymph node metastases in 110 Dukes’ stage C, CRC cases by immunohistochemical methods, related to patients’ clinical outcomes. NF-κB, p53, and Ki-67 expressions were significantly higher in the metastatic lymph nodes compared to the primary tumor tissues (, , and , resp.). In the metastatic lymph nodes NF-κB expression was correlated with both p53 (, ) and Ki-67 (, ) expressions. The univariant and multivariant analyses showed that only “pT stage” preserved an independent prognostic significance for recurrence-free survival rates and 5-year overall survival rates ( for both). Metastatic cells can acquire different biological characteristics compared to their primaries. Elucidation of properties acquired by metastatic cells is important in order to better determine prognosis, reverse drug resistance, and discover new treatment alternatives. Ibrahim Meteoglu, Ibrahim Halil Erdogdu, Pars Tuncyurek, Adil Coskun, Nil Culhaci, Muhan Erkus, and Sabri Barutca Copyright © 2015 Ibrahim Meteoglu et al. All rights reserved. Role of Gut Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease Sun, 05 Apr 2015 14:01:03 +0000 Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, and its incidence is increasing year by year. Many efforts have been made to investigate the pathogenesis of this disease. Since 1998 when Marshall proposed the conception of “gut-liver axis,” more and more researchers have paid close attention to the role of gut barrier function in the pathogenesis of NAFLD. The four aspects of gut barrier function, including physical, chemical, biological, and immunological barriers, are interrelated closely and related to NAFLD. In this paper, we present a summary of research findings on the relationship between gut barrier dysfunction and the development of NAFLD, aiming at illustrating the role of gut barrier function in the pathogenesis of this disease. Xin Dai and Bangmao Wang Copyright © 2015 Xin Dai and Bangmao Wang. All rights reserved. Risk Factors for Migration, Fracture, and Dislocation of Pancreatic Stents Sun, 05 Apr 2015 13:07:12 +0000 Aim. To analyze the risk factors for pancreatic stent migration, dislocation, and fracture in chronic pancreatitis patients with pancreatic strictures. Materials and Methods. Endoscopic stent placements (total 386 times) were performed in 99 chronic pancreatitis patients with pancreatic duct stenosis at our institution between April 2006 and June 2014. We retrospectively examined the frequency of stent migration, dislocation, and fracture and analyzed the patient factors and stent factors. We also investigated the retrieval methods for migrated and fractured stents and their success rates. Results. The frequencies of stent migration, dislocation, and fracture were 1.5% (5/396), 0.8% (3/396), and 1.2% (4/396), respectively. No significant differences in the rates of migration, dislocation, or fracture were noted on the patient factors (etiology, cases undergoing endoscopic pancreatic sphincterotomy, location of pancreatic duct stenosis, existence of pancreatic stone, and approach from the main or minor papilla) and stent factors (duration of stent placement, numbers of stent placements, stent shape, diameter, and length). Stent retrieval was successful in all cases of migration. In cases of fractured stents, retrieval was successful in 2 of 4 cases. Conclusion. Stent migration, fracture, and dislocation are relatively rare, but possible complications. A good understanding of retrieval techniques is necessary. Yoshiaki Kawaguchi, Jung-Chun Lin, Yohei Kawashima, Atsuko Maruno, Hiroyuki Ito, Masami Ogawa, and Tetsuya Mine Copyright © 2015 Yoshiaki Kawaguchi et al. All rights reserved. Clinical Outcomes and Quality of Life in Recipients of Livers Donated after Cardiac Death Wed, 01 Apr 2015 14:58:51 +0000 Donation after cardiac death (DCD) has expanded in the last decade in the US; however, DCD liver utilization has flattened in recent years due to poor outcomes. We examined clinical and quality of life (QOL) outcomes of DCD recipients by conducting a retrospective and cross-sectional review of patients from 2003 to 2010. We compared clinical outcomes of DCD recipients () to those of donation after brain death (DBD) liver recipients () during the same time period. DCD recipients had significantly lower rates of 5-year graft survival () and a trend toward lower rates of 5-year patient survival () when compared to the DBD cohort. In order to examine QOL outcomes in our cohorts, we administered the Short Form Liver Disease Quality of Life questionnaire to 30 DCD and 60 DBD recipients. The DCD recipients reported lower generic and liver-specific QOL. We further stratified the DCD cohort by the presence of ischemic cholangiopathy (IC). Patients with IC reported lower QOL when compared to DBD recipients and those DCD recipients without IC (). While the results are consistent with clinical experience, this is the first report of QOL in DCD recipients using standardized measures. These data can be used to guide future comparative effectiveness studies. Neehar D. Parikh, Anton I. Skaro, Daniela P. Ladner, Vadim Lyuksemburg, Joshua G. Cahan, Amna Daud, and Zeeshan Butt Copyright © 2015 Neehar D. Parikh et al. All rights reserved. The Utility of Capsule Endoscopy in Patients under 50 Years of Age with Recurrent Iron Deficiency Anaemia: Is the Juice Worth the Squeeze? Wed, 01 Apr 2015 13:58:47 +0000 Background and Aims. The role of capsule endoscopy (CE) in the <50 years of age patients with iron deficiency anaemia (IDA) remains unclear. We aim to assess its utility in this cohort. Methods. All patients referred for CE for recurrent IDA were included retrospectively. Patients were divided into Group 1 (<50 years) and Group 2 (≥50 years). Results. There were 971 patients with recurrent IDA and 28% belonged to Group 1. The mean age was 40 years in this group with a DY of 28% (). Significant diagnoses included erosions and ulcers (26%; ), small bowel (SB) angioectasia (AE) (10%; ), SB tumours (3%; ), Crohn’s disease (3%; ), SB bowel strictures (1%; ), and SB varices (1%; ). On logistic regression, the presence of diabetes () and the use of warfarin () was associated with increased DY. The DY in Group 2 was 38% which was significantly higher than in Group 1 (). While SB tumours were equally common in both groups, AE was commoner in Group 2 (). Conclusion. A significant proportion of patients <50 years are referred for CE. Although the DY is lower compared to those ≥50 years, significant pathology is found in this age group. CE is advisable in patients <50 years old with recurrent IDA and negative bidirectional endoscopies. Prabhjot Singh Sidhu, Mark E. McAlindon, Kaye Drew, and Reena Sidhu Copyright © 2015 Prabhjot Singh Sidhu et al. All rights reserved. Molecular Pathogenesis of MALT Lymphoma Wed, 01 Apr 2015 12:05:02 +0000 Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT), also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis. Katharina Troppan, Kerstin Wenzl, Peter Neumeister, and Alexander Deutsch Copyright © 2015 Katharina Troppan et al. All rights reserved. Clinical Impact of Prophylactic Antibiotic Treatment for Self-Expandable Metallic Stent Insertion in Patients with Malignant Colorectal Obstruction Tue, 31 Mar 2015 16:46:55 +0000 Purpose. The aim of this study was to determine the efficacy of prophylactic antibiotics (PA) for reducing the infectious complications and the potential risk factors responsible for the infectious complications after stent insertion for malignant colorectal obstruction. Methods. We performed a retrospective review of 224 patients who underwent self-expandable metallic stent (SEMS) insertion for malignant colorectal obstruction from May 2004 to December 2012. Results. There were 145 patients in the PA group and 79 in non-PA group. The CRP level in PA group was significantly higher than that in non-PA. Abdominal tenderness and mechanical ileus were significantly more frequent in PA group than those in non-PA. The frequency of post-SEMS insertion fever, systemic inflammatory response syndrome (SIRS), and bacteremia was not significantly different between PA and non-PA groups. In multivariate analysis, the CRP level was risk factor related to post-SEMS insertion SIRS. However, in propensity score matching analysis, there was no independent risk factor related to post-SEMS insertion fever, SIRS, and bacteremia. Conclusion. The use of PA in patients with malignant colorectal obstruction may be not effective to prevent the development of infectious complications after SEMS insertion. Jong-Sun Kim, Wan-Sik Lee, Cho-Yun Chung, Hyung-Chul Park, Dae-Seong Myung, Chan-Young Oak, Mi-Young Kim, Mi-Ok Jang, Seung-Ji Kang, Hee-Chang Jang, Sung-Bum Cho, Hyun-Soo Kim, and Young-Eun Joo Copyright © 2015 Jong-Sun Kim et al. All rights reserved. Differential Expression of Motilin Receptor in Various Parts of Gastrointestinal Tract in Dogs Tue, 31 Mar 2015 14:11:57 +0000 Objectives. The presence of motilin receptor in the GI tract of different animal species has been verified. However, the quantitation of motilin receptor expression in different regions of the GI tract remains unclear. The aim of this study was to investigate the expression of motilin receptor in the GI tract and semiquantitatively compare the expression difference in different GI regions in dogs. Methods. Antrum, duodenum, jejunum, ileum, proximal colon, middle colon, and distal colon were obtained from various parts of the GI tract of six sacrificed dogs. The distribution of motilin receptor was determined by immunohistochemistry. The expression levels of motilin receptor mRNA in different regions were measured by RT-PCR. Results. Motilin receptor was expressed throughout the GI tract in dogs. Multiple comparisons of the mean motilin receptor mRNA expression among various regions were significant . Motilin receptor mRNA was extensively expressed in duodenum, followed by ileum, jejunum, proximal colon, antrum, middle colon, and distal colon. Immunohistochemistry revealed that motilin receptor immunoreactivity was observed only in the enteric nervous system. Conclusion. Motilin receptor is expressed differentially along the GI tract in dogs. The significantly high expression of motilin receptor mRNA is found in the duodenum. Yu He, Hui Wang, DongYan Yang, ChengYan Wang, LanLan Yang, and Chunxiang Jin Copyright © 2015 Yu He et al. All rights reserved. Endoscopic Retrieval Technique of Proximally Migrated Pancreatic Stents: A Retrospective Study in a Tertiary Centre Tue, 31 Mar 2015 13:54:05 +0000 Background. There were scarce trials concerning the treatments and outcomes of proximal pancreatic stent migration. Herein, we did a retrospective study to discuss this problem from an endoscopist’s point of view. Patients and Methods. From January 2009 to June 2014, patients with proximally migrated pancreatic duct stents were identified. Their clinical information was viewed. Retrieval techniques, success rates, and adverse events were analyzed. Results. A total of 36 procedures were performed in 34 patients; the median age of the patients was 53 years, with 17 males and 17 females. Eight patients’ pancreatic duct stents could still be seen in the major or minor papilla and were pulled out with a snare forceps or a grasping forceps; in the remaining 28 procedures, the management was somewhat thorny; the retrieval called for several devices. Final success was achieved in 31 patients. No adverse event was observed in the process of ERCP procedures, 5 patients developed post-ERCP pancreatitis (PEP), 1 patient got infection, and 1 patient had haemorrhage. Conclusions. Endoscopic retrieval of migrated pancreatic stent is safe and less invasive; nonetheless, attention should be paid so as to reduce the incidence and degree of related adverse events, especially PEP. Yi Lu, Zheng Jin, Jia-chuan Wu, Li-ke Bie, and Biao Gong Copyright © 2015 Yi Lu et al. All rights reserved. Circulating Oxidized Low-Density Lipoproteins and Antibodies against Oxidized Low-Density Lipoproteins as Potential Biomarkers of Colorectal Cancer Tue, 31 Mar 2015 13:33:24 +0000 Introduction. The aim of the study was evaluation of the diagnostic utility of serum oxidized low-density lipoproteins (oxLDL), antibodies against oxLDLs (o-LAB), and CEA as risk markers of colorectal cancer (CRC). Material and Methods. The serum levels of study factors were measured in 73 patients with CRC and in 35 healthy controls who were gender- and BMI-matched to the study group. Concentrations of oxLDL, o-LAB, and CEA were detected in ELISA tests. Serum lipids, lipoproteins, and glucose levels were also coestimated. Results. Age and o-LAB were significant factors of CRC presence, but results of logistic regression analysis showed that both were weak predictors of CRC risk. Concentration of o-LAB was significantly higher in colon cancer than in rectal cancer, especially when the cancer was located in the right section of colon. Serum CEA levels were significantly elevated in the advanced stage of disease, primary tumor progression, angiolymphatic invasion, and presence of distant metastasis. Conclusions. Obtained results have demonstrated that oxLDL and o-LAB were not satisfactory risk markers of CRC. Although significant relation between o-LAB level and CRC is observed, it may be rather the result of individual differences in the host immune responses against cancer. Dorota Diakowska, Krzysztof Grabowski, Mirosław Nienartowicz, Paweł Zarębski, Kamila Fudalej, and Krystyna Markocka-Mączka Copyright © 2015 Dorota Diakowska et al. All rights reserved. Hepatic Overexpression of GRP94 in a Rabbit Model of Parenteral Nutrition-Associated Liver Disease Mon, 30 Mar 2015 12:06:12 +0000 Objective. To use a rabbit model of parenteral nutrition-associated liver disease (PNALD) to study changes of the endoplasmic reticulum stress (ERS) marker glucose regulatory protein 94 (GRP94) and determine its role in the pathogenesis of PNALD. Methods. A rabbit PNALD model total parenteral nutrition (TPN) group was established. A corresponding control group received breast-feeding for one week. Serum biochemical parameters were measured and liver histological examinations were performed. The level of GRP94 mRNA and protein were measured. Results. The results showed that the serum TBIL, DBIL, and γ-GT levels in the TPN group were significantly higher than those in the control group, while levels of serum ALB in TPN group were significantly lower than those in the control group. The immunohistochemistry results showed that the protein expression level of GRP94 in the liver of TPN group was significantly increased compared with the control group. The RT-PCR results showed that the level of GRP94 mRNA in the liver of the TPN group was significantly higher compared with the control group. Conclusions. The mRNA and protein levels of GRP94 in the TPN group were both significantly increased, indicating that ERS may be directly related to the occurrence and development of PNALD. Xueping Zhu, Xiaomin Zhang, Lingling Yu, Yumin Xu, Xing Feng, and Jian Wang Copyright © 2015 Xueping Zhu et al. All rights reserved.