Gastroenterology Research and Practice The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. The Interplay of the Gut Microbiome, Bile Acids, and Volatile Organic Compounds Tue, 03 Mar 2015 10:56:53 +0000 Background. There has been an increasing interest in the use of volatile organic compounds (VOCs) as potential surrogate markers of gut dysbiosis in gastrointestinal disease. Gut dysbiosis occurs when pathological imbalances in gut bacterial colonies precipitate disease and has been linked to the dysmetabolism of bile acids (BA) in the gut. BA metabolites as a result of microbial transformations act as signaling molecules and have demonstrated regulation of intestinal homeostasis through the TGR5 and FXR receptors by inhibiting inflammation, preventing pathogen invasion, and maintaining cell integrity. The presence of VOC footprints is the resultant effect to gut microbiome substrate fermentation. Aim. To review the role of the gut microbiome and bile acid signaling in intestinal homeostasis and the resultant use of VOCs as potential noninvasive surrogate biomarkers in gut dysbiosis. Methods. A systematic search on PubMed and Medline databases was performed to identify articles relevant to gut dysbiosis, BA metabolism, and VOCs. Conclusions. The host and presence of the gut microbiome appear to regulate the BA pool size. A dysbiotic gut microbiome results in disrupted intestinal homeostasis, which may be reflected by VOCs, differentiating those who are healthy and those with disease. Nidhi M. Sagar, Ian A. Cree, James A. Covington, and Ramesh P. Arasaradnam Copyright © 2015 Nidhi M. Sagar et al. All rights reserved. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients Tue, 03 Mar 2015 10:01:55 +0000 Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline ( and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype. Alessandro Grasso, Federica Malfatti, Gabriella Andraghetti, Simona Marenco, Chiara Mazzucchelli, Sara Labanca, Renzo Cordera, Roberto Testa, and Antonino Picciotto Copyright © 2015 Alessandro Grasso et al. All rights reserved. Analysis of the Serum Bile Acid Composition for Differential Diagnosis in Patients with Liver Disease Tue, 03 Mar 2015 06:17:11 +0000 Objectives. We determined the serum bile acid (BA) composition in patients with liver diseases and healthy volunteers to investigate the relationship between the etiologies of liver disease and BA metabolism. Material and Methods. Sera from 150 patients with liver diseases and 46 healthy volunteers were obtained. The serum concentrations of the 16 different BAs were determined according to the LC-MS/MS method and were compared between the different liver diseases. Results. A total of 150 subjects, including patients with hepatitis C virus (HCV) (), hepatitis B virus (HBV) (), alcoholic liver disease (ALD) (), biliary tract disease (), nonalcoholic fatty liver disease (NAFLD) (), and other liver diseases (), were recruited. The levels of UDCA and GUDCA were significantly higher in the ALD group, and the levels of DCA and UDCA were significantly lower in the biliary tract diseases group than in viral hepatitis group. In the UDCA therapy (−) subgroup, a significantly lower level of TLCA was observed in the ALD group, with lower levels of CDCA, DCA, and GLCA noted in biliary tract diseases group compared to viral hepatitis group. Conclusions. Analysis of the BA composition may be useful for differential diagnosis in liver disease. Tomonori Sugita, Katsushi Amano, Masanori Nakano, Noriko Masubuchi, Masahiro Sugihara, and Tomokazu Matsuura Copyright © 2015 Tomonori Sugita et al. All rights reserved. Bypass during Liver Transplantation: Anachronism or Revival? Liver Transplantation Using a Combined Venovenous/Portal Venous Bypass—Experiences with 163 Liver Transplants in a Newly Established Liver Transplantation Program Mon, 02 Mar 2015 16:09:29 +0000 Introduction. The venovenous/portal venous (VVP) bypass technique has generally become obsolete in liver transplantation (LT) today. We evaluated our experience with 163 consecutive LTs that used a VVP bypass. Patients and Methods. The liver transplant program was started in our center in 2010. LTs were performed using an extracorporal bypass device. Results. Mean operative time was 269 minutes and warm ischemic time 43 minutes. The median number of transfusion of packed cells and plasma was 7 and 14. There was no intraoperative death, and the 30-day mortality was 3%. Severe bypass-induced complications did not occur. Discussion. The introduction of a new LT program requires maximum safety measures for all of the parties involved. Both surgical and anaesthesiological management (reperfusion) can be controlled very reliably using a VVP bypass device. Particularly when using marginal grafts, this approach helps to minimise both surgical and anaesthesiological complications in terms of less volume overload, less use of vasopressive drugs, less myocardial injury, and better peripheral blood circulation. Conclusion. Based on our experiences while establishing a new liver transplantation program, we advocate the reappraisal of the extracorporeal VVP bypass. Anne Mossdorf, Florian Ulmer, Karsten Junge, Christoph Heidenhain, Marc Hein, Ilknur Temizel, Ulf Peter Neumann, Wenzel Schöning, and Maximilian Schmeding Copyright © 2015 Anne Mossdorf et al. All rights reserved. Real-Life Report on Chemoembolization Using DEBIRI for Liver Metastases from Colorectal Cancer Thu, 26 Feb 2015 11:43:34 +0000 Background. Transarterial chemoembolization (TACE) has been investigated in patients with liver metastases from colorectal cancer (LMCRC). Limited experience and available data suggest that TACE can achieve disease stabilization or improvement, even in heavily pretreated patients. Methods. Patients with LMCRC, ECOG 0–2, who failed at least 1 line of systemic chemotherapy, received embolizations with 2 mL of microspheres preloaded with 100 mg of irinotecan. Beads were delivered selectively into hepatic arteries. Primary endpoint was overall survival (OS), analyzed using the Kaplan-Meier method. Secondary endpoint was safety, assessed using CTCAE version 4.0. Results. 27 patients were treated using DEBIRI. Patient median age was 57 years (range was 45–82 years). The median number of total embolizations was 1.3 (range 1–3). The median OS was 5.4 months (95% CI; 1.1–22.7 months). The most reported postembolization events were nausea (8/27), vomiting (6/27), right upper quadrant pain (16/27), fatigue (9/27), and the development of ascites (6/27). 5/26 patients required hospitalization after TACE for severe pain. Hospitalization was also required for 1 case of allergic reaction and 1 case of infection. Conclusion. Our data suggest that TACE with DEBIRI could be efficacious in a palliative setting for patients with LMCRC, but they do not necessarily support routine use in clinical practice. M. Stutz, A. Mamo, D. Valenti, A. Hausvater, T. Cabrera, P. Metrakos, P. Chaudhury, G. Steacy, E. Garoufalis, and P. Kavan Copyright © 2015 M. Stutz et al. All rights reserved. Interval Cancers in a Population-Based Screening Program for Colorectal Cancer in Catalonia, Spain Tue, 24 Feb 2015 09:14:52 +0000 Objective. To analyze interval cancers among participants in a screening program for colorectal cancer (CRC) during four screening rounds. Methods. The study population consisted of participants of a fecal occult blood test-based screening program from February 2000 to September 2010, with a 30-month follow-up (n = 30,480). We used hospital administration data to identify CRC. An interval cancer was defined as an invasive cancer diagnosed within 30 months of a negative screening result and before the next recommended examination. Gender, age, stage, and site distribution of interval cancers were compared with those in the screen-detected group. Results. Within the study period, 97 tumors were screen-detected and 74 tumors were diagnosed after a negative screening. In addition, 17 CRC (18.3%) were found after an inconclusive result and 2 cases were diagnosed within the surveillance interval (2.1%). There was an increase of interval cancers over the four rounds (from 32.4% to 46.0%). When compared with screen-detected cancers, interval cancers were found predominantly in the rectum (OR: 3.66; 95% CI: 1.51–8.88) and at more advanced stages (). Conclusion. There are large numbers of cancer that are not detected through fecal occult blood test-based screening. The low sensitivity should be emphasized to ensure that individuals with symptoms are not falsely reassured. M. Garcia, X. Domènech, C. Vidal, E. Torné, N. Milà, G. Binefa, L. Benito, and V. Moreno Copyright © 2015 M. Garcia et al. All rights reserved. Early Laparoscopic Cholecystectomy with Continuous Pressurized Irrigation and Dissection in Acute Cholecystitis Tue, 24 Feb 2015 09:11:08 +0000 Background. The aim of this study was to evaluate the preliminary results of a new dissection technique in acute cholecystitis. Material and Method. One hundred and forty-nine consecutive patients with acute cholecystitis were operated on with continuous pressurized irrigation and dissection technique. The diagnosis of acute cholecystitis was based on clinical, laboratory, and radiological evidences. Age, gender, time from symptom onset to hospital admission, operative risk according to the American Society of Anesthesiologists (ASA) score, white blood cell count, C-reactive protein test levels, positive findings of radiologic evaluation of the patients, operation time, perioperative complications, mortality, and conversion to open surgery were prospectively recorded. Results. Of the 149 patients, 87 (58,4%) were female and 62 (41,6%) were male. The mean age was years. The median time from symptom onset to hospital admission 3.2 days (range, 1–6). There were no major complications such as bile leak, common bile duct injury or bleeding. Subhepatic liquid collection occurred in 3 of the patients which was managed by percutaneous drainage. Conversion to open surgery was required in four (2,69%) patients. There was no mortality in the study group. Conclusion. Laparoscopic cholecystectomy with continuous pressurized irrigation and dissection technique in acute cholecystitis seems to be an effective and reliable procedure with low complication and conversion rates. I. Ozsan, O. Yoldas, T. Karabuga, U. M. Yıldırım, H. Y. Cetin, O. Alpdoğan, and U. Aydin Copyright © 2015 I. Ozsan et al. All rights reserved. Feasibility of Endoscopic Resection for Sessile Nonampullary Duodenal Tumors: A Multicenter Retrospective Study Tue, 24 Feb 2015 07:03:33 +0000 Objectives. Sessile nonampullary duodenal tumors (SNADTs) are relatively rare and endoscopic resection of these lesions is considered more challenging than in other parts of the gastrointestinal tract. The aim of this study was to evaluate the feasibility of endoscopic resection for SNADT. Methods. Medical records including endoscopic resection for SNADT from July 2002 to July 2013 from 5 centers affiliated to The Catholic University of Korea were reviewed retrospectively. Demographic features and clinical outcomes such as complete resection and complications were analyzed. Results. A total of 56 lesions from 54 patients were enrolled in this study. Forty-five lesions were resected by endoscopic mucosal resection (EMR), 6 lesions by endoscopic submucosal dissection (ESD), and 5 lesions by simple polypectomy. Histologic examination after endoscopic resection revealed adenocarcinoma in 2, low grade adenoma in 25, high grade adenoma in 11, and carcinoid tumor in 18 lesions. En bloc resection rates and histological complete resection rates were 78.6% (44/56) and 80.0% (28/35), respectively. Bleeding which required additional endoscopic intervention occurred in 1.8% (1/56) and perforation in 7.1% (4/56). There was no procedure-related mortality. Conclusions. Endoscopic resection techniques including ESD might be safe and effective modalities for the management of SNADT. Sung Min Park, Joo Ho Ham, Byung-Wook Kim, Joon Sung Kim, Chang Whan Kim, Jin Il Kim, Chul Hyun Lim, and Jung Hwan Oh Copyright © 2015 Sung Min Park et al. All rights reserved. Association between Portal Vein Thrombosis and Survival in Non-Liver-Transplant Patients with Liver Cirrhosis: A Systematic Review of the Literature Tue, 24 Feb 2015 06:48:26 +0000 A systematic review of the literature was performed to analyze the association between portal vein thrombosis (PVT) and survival in non-liver-transplant patients with liver cirrhosis. PubMed, EMBASE, and Cochrane Library databases were searched for all relevant papers which evaluated the prognostic value of PVT in predicting the survival of liver cirrhosis. Meta-analyses were not conducted because the ways of data expression and lengths of follow-up were heterogeneous among studies. Overall, 13 papers were included. The 5-day, 6-week, and 1-year mortality were investigated in 1, 3, and 1 studies, respectively; and all of them were not significantly different between cirrhotic patient with and without PVT. By comparison, the 3-year mortality was reported in 1 study; and it was significantly increased by the presence of PVT. The overall mortality was analyzed in 5 studies; and the association with overall mortality and PVT was significant in 4 studies, but not in another one. However, as for the cirrhotic patients undergoing surgical or interventional shunts, the overall mortality was not significantly associated with the presence of PVT in 4 studies. In conclusion, the presence of PVT might be associated with the long-term mortality in non-liver-transplant patients with liver cirrhosis, but not with the short-term mortality. Xingshun Qi, Junna Dai, Man Yang, Weirong Ren, Jia Jia, and Xiaozhong Guo Copyright © 2015 Xingshun Qi et al. All rights reserved. Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen Mon, 23 Feb 2015 12:15:05 +0000 Background and Aim. Although mercury is involved in several immunological diseases, nothing is known about its implication in celiac disease. Our aim was to evaluate blood and urinary levels of mercury in celiac patients. Methods. We prospectively enrolled 30 celiac patients (20 treated with normal duodenal mucosa and 10 untreated with duodenal atrophy) and 20 healthy controls from the same geographic area. Blood and urinary mercury concentrations were measured by means of flow injection inductively coupled plasma mass spectrometry. Enrolled patients underwent dental chart for amalgam fillings and completed a food-frequency questionnaire to evaluate diet and fish intake. Results. Mercury blood/urinary levels were , and in untreated CD, treated CD, and healthy controls, respectively. Resulting mercury levels were significantly higher in celiac patients following a gluten-free diet. No differences were found regarding fish intake and number of amalgam fillings. No demographic or clinical data were significantly associated with mercury levels in biologic samples. Conclusion. Data demonstrate a fourfold increase of mercury blood levels in celiac patients following a gluten-free diet. Further studies are needed to clarify its role in celiac mechanism. Luca Elli, Valentina Rossi, Dario Conte, Anna Ronchi, Carolina Tomba, Manuela Passoni, Maria Teresa Bardella, Leda Roncoroni, and Gianpaolo Guzzi Copyright © 2015 Luca Elli et al. All rights reserved. Beneficial Effects of Combining Computed Tomography Enteroclysis/Enterography with Capsule Endoscopy for Screening Tumor Lesions in the Small Intestine Sun, 22 Feb 2015 13:56:23 +0000 Aim. To compare the efficacy of using computed tomography enteroclysis/enterography (CTE), capsule endoscopy (CE), and CTE with CE for diagnosing tumor lesions in the small intestine. Materials and Methods. We included 98 patients who underwent CE during the observation period and were subjected to CTE at our hospital from April 2008 to May 2014. Results. CTE had a significantly higher sensitivity than CE (84.6% versus 46.2%, ), but there were no significant differences in specificity, positive or negative predictive values, or diagnostic accuracy rates. The sensitivity of CTE/CE was 100%, again significantly higher than that of CE . The difference in specificity between CTE/CE and CE was not significant, but there were significant differences in positive predictive values (100% for CTE/CE versus 66.7% for CE, ), negative predictive values (100% versus 92.1%, ), and diagnostic accuracy rate (100% versus 89.8%, ). The diagnostic accuracy rate was also significantly higher in CTE/CE versus CTE (100% versus 95.9%, ). Conclusion. Our findings suggested that a combination of CTE and CE was useful for screening tumor lesions in the small intestine. This trial is registered with number UMIN000016154. Hiroaki Shibata, Shinichi Hashimoto, Kensaku Shimizu, Ryo Kawasato, Tomohiro Shirasawa, Takayuki Yokota, Hideko Onoda, Takeshi Okamoto, Jun Nishikawa, Naofumi Matsunaga, and Isao Sakaida Copyright © 2015 Hiroaki Shibata et al. All rights reserved. The Effectiveness of Short Message Service to Assure the Preparation-to-Colonoscopy Interval before Bowel Preparation for Colonoscopy Sun, 22 Feb 2015 07:28:21 +0000 Background/Aims. The preparation-to-colonoscopy (PC) interval is one of several important factors for the bowel preparation. Short message service (SMS) reminder from a cellular phone has been suggested to improve compliance in various medical situations. We evaluated the effectiveness of SMS reminders to assure the PC interval for colonoscopy. Methodology. This prospective randomized study was investigator blinded. In the No-SMS group, patients took the first 2 L polyethylene glycol (PEG) between 6 and 8 PM on the day before colonoscopy and the second 2 L PEG approximately 6 hours before the colonoscopy without SMS. In the SMS group, patients took first 2 L PEG in the same manner as the No-SMS group and the second 2 L PEG after receiving an SMS 6 hours before the colonoscopy. Results. The SMS group had a lower score than the No-SMS group, according to the Ottawa Bowel Preparation Scale . Multivariate logistic regression analysis showed that compliance with diet instructions (odds ratio (OR) 2.109; 95% confidence interval (CI), 1.11–3.99, ) and intervention using SMS ((OR) 2.329; 95% (CI), 1.34–4.02, ) were the independent significant factors for satisfactory bowel preparation. Conclusions. An SMS reminder to assure PC interval improved the bowel preparation quality for colonoscopy with bowel preparation. Jongha Park, Tae-Oh Kim, Nae-Young Lee, Hyoungjun Kim, Eun Hee Seo, Nae-Yun Heo, Seung Ha Park, and Young-Soo Moon Copyright © 2015 Jongha Park et al. All rights reserved. Risk Factors and Medico-Economic Effect of Pancreatic Fistula after Pancreaticoduodenectomy Thu, 19 Feb 2015 12:36:21 +0000 The study aimed to uncover the risk factors for the new defined pancreatic fistula (PF) and clinical related PF (CR-PF) after pancreaticoduodenectomy (PD) surgery and to evaluate the medico-economic effect of patients. A total of 412 patients were classified into two groups according to different criteria, PF and NOPF according to PF occurrence: CR-PF (grades B and C) and NOCR-PF (grade A) based on PF severity. A total of 28 factors were evaluated by univariate and multivariate logistic regression test. Hospital charges and stays of these patients were assessed. The results showed that more hospital stages and charges are needed for patients in PF and CR-PF groups than in NOPF and NOCR-PF groups (). The excessive drinking, soft remnant pancreas, preoperative albumin, and intraoperative blood transfusion are risk factors affecting both PF and CR-PF incidence. More professional surgeons can effectively reduce the PF and CR-PF incidence. Patients with PF and CR-PF need more hospital costs and stages than that in NOPF and NOCR-PF groups. It is critical that surgeons know the risk factors related to PF and CR-PF so as to take corresponding therapeutic regimens for each patient. Renping Huang, Bing Liu, Hua Chen, Xuewei Bai, Rui Kong, Gang Wang, Yongwei Wang, Bei Sun, and Yinghui Guan Copyright © 2015 Renping Huang et al. All rights reserved. Hepatitis B Virus-Related Glomerulonephritis: Not a Predominant Cause of Proteinuria in Korean Patients with Chronic Hepatitis B Wed, 18 Feb 2015 12:52:50 +0000 Background/Aims. Hepatitis B virus (HBV) can form immune complexes which may result in various types of glomerulonephritis (GN). However, proteinuria can occur because of other kidney diseases besides HBV-related GN (HBV-GN). The aim of this study is to elucidate the causes of proteinuria and report on the clinical outcomes of HBV-GN. Methods. We reviewed the medical records of patients positive for serum hepatitis B surface antigen who underwent renal biopsies due to proteinuria at a tertiary medical center in Korea. Results. A total of 55 patients were included. HBV-GN was diagnosed in 20 (36.4%) of the patients by confirming the presence of immune complexes (12 of 13 membranoproliferative glomerulonephritis, 7 of 8 membranous glomerulonephritis, and 1 of 13 immunoglobulin A nephropathy). Twenty-one patients had other types of GN. A total of 13 (65%) HBV-GN patients were treated with antiviral agents for a median of 11 months. However, the degrees of proteinuria were not significantly reduced in the antiviral intervention group when compared to the control group. Conclusions. Proteinuria can be caused by various glomerular diseases and HBV-GN accounts for one-third of total GN cases. Well-designed prospective study is needed to assess whether antiviral therapy against HBV infection may improve the prognosis of HBV-GN. Jeong-Ju Yoo, Jeong-Hoon Lee, Jung-Hwan Yoon, Minjong Lee, Dong Hyeon Lee, Yuri Cho, Eun Sun Jang, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, and Hyo-Suk Lee Copyright © 2015 Jeong-Ju Yoo et al. All rights reserved. From Molecular Classification to Targeted Therapeutics: The Changing Face of Systemic Therapy in Metastatic Gastroesophageal Cancer Tue, 17 Feb 2015 14:08:48 +0000 Histological classification of adenocarcinoma or squamous cell carcinoma for esophageal cancer or using the Lauren classification for intestinal and diffuse type gastric cancer has limited clinical utility in the management of advanced disease. Germline mutations in E-cadherin (CDH1) or mismatch repair genes (Lynch syndrome) were identified many years ago but given their rarity, the identification of these molecular alterations does not substantially impact treatment in the advanced setting. Recent molecular profiling studies of upper GI tumors have added to our knowledge of the underlying biology but have not led to an alternative classification system which can guide clinician’s therapeutic decisions. Recently the Cancer Genome Atlas Research Network has proposed four subtypes of gastric cancer dividing tumors into those positive for Epstein-Barr virus, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. Unfortunately to date, many phase III clinical trials involving molecularly targeted agents have failed to meet their survival endpoints due to their use in unselected populations. Future clinical trials should utilize molecular profiling of individual tumors in order to determine the optimal use of targeted therapies in preselected patients. Adrian Murphy and Ronan J. Kelly Copyright © 2015 Adrian Murphy and Ronan J. Kelly. All rights reserved. Comparisons of Esophageal Function Tests between Chinese and British Patients with Gastroesophageal Reflux Disease Mon, 16 Feb 2015 14:06:29 +0000 Objective. To investigate the esophageal function tests in British and Chinese patients with gastroesophageal reflux disease (GERD). Methods. Patients with GERD were selected from the functional gut clinic, London, and digestive department, Beijing Chao-Yang Hospital, after taking the examinations of High-resolution Manometry and Impedance (HRiM) and 24-hour Multi-Channel Intraluminal Impedance and pH Recording (MII/pH) between 2013 and 2014. Chinese healthy volunteers who undertook HRiM were also selected as control group. Results. Fifty-nine British and 82 Chinese patients with GERD and 62 Chinese healthy volunteers were entered. Values for British patients, Chinese patients, and healthy volunteers were as follows: Lower esophageal sphincter pressure (LESP) , , and  mmHg, peristalsis (normal/small break/large break) 24/12/23, 44/10/28, and 57/1/4, total bolus transit time (TBTT) , , and  s, and complete bolus transit rate (CBTR) , , and %, respectively. Stepwise linear regression analysis showed that age, gender, and ethnicity did not have significant effect on LESP, TBTT, esophageal peristalsis, and CBTR in patients with GERD. Conclusions. British and Chinese patients with GERD presented similar values of LESP, TBTT, and impaired esophageal peristalsis and CBTR. Feng Gao, Samantha Leach, Jian Yu Hao, Zhan Min Shang, and Anthony Robert Hobson Copyright © 2015 Feng Gao et al. All rights reserved. Recurrent Posterior Strokes in Inflammatory Bowel Disease Patients Sun, 15 Feb 2015 12:29:06 +0000 Objective. To describe the stroke characteristics of patients with a history of inflammatory bowel disease (IBD). Background. A hypercoagulable state associated with IBD has been frequently implicated as a risk factor for ischemic stroke. Variable mechanisms and infrequent occurrence limit prospective clinical research on the association between IBD and stroke. Methods. We retrospectively reviewed consecutive patients with acute ischemic stroke presenting to our medical center from 7/2008 to 9/2013. Patients with a history of IBD were identified. Clinical variables were abstracted from our prospective stroke registry. Results. Over the period of five years we identified only three patients with a documented history of IBD. Each of these patients presented three times to our hospital with new strokes. Patients presented outside the window for intravenous tPA treatment on 8/9 admissions. Each one of our patients had posterior strokes on at least two separate occasions. Hypercoagulation panel showed elevated factor VIII with or without concomitant elevation of Von Willebrand factor (vWF) during almost every admission (8/9 admissions). Only one admission was associated with IBD flare. Conclusion. The association between IBD and posterior strokes is a novel finding. Factor VIII elevation may serve as a biomarker of a peristroke hypercoagulable state in patients with IBD. Amir Shaban, Brett Hymel, Maria Chavez-Keatts, Jordan J. Karlitz, and Sheryl Martin-Schild Copyright © 2015 Amir Shaban et al. All rights reserved. Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function Thu, 12 Feb 2015 14:05:34 +0000 Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragment ) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer and measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD. Luca Pastorelli, Elena Dozio, Laura Francesca Pisani, Massimo Boscolo-Anzoletti, Elena Vianello, Nadia Munizio, Luisa Spina, Gian Eugenio Tontini, Flora Peyvandi, Massimiliano Marco Corsi Romanelli, and Maurizio Vecchi Copyright © 2015 Luca Pastorelli et al. All rights reserved. Gastric Collision Tumors: An Insight into Their Origin and Clinical Significance Thu, 12 Feb 2015 09:11:35 +0000 Collision tumors are rare neoplasms displaying two distinct cell populations developing in juxtaposition to one another without areas of intermingling. They are rare entities with only 63 cases described in English literature. Tumors encountered are gastric adenocarcinomas colliding with lymphomas, gastrointestinal stromal tumors, squamous cell carcinomas, and neuroendocrine tumors. Their cell origin is obsolete by the time of diagnosis. Different tumorigenesis theories have been suggested to explain their behavior, yet none has managed to provide satisfactory explanation for all cases. Clinically they are indistinguishable from the dominant tumor. Lack of data does not allow detailed assessment of their behavior yet they seem aggressive neoplasms with dismal prognosis. The majority of cases have been diagnosed postoperatively during histologic examination of specimens. There are no guidelines or concrete evidence to support best way of adjuvant or other types of treatment. However, these rare neoplasms might help in unlocking secrets of cancer behavior including tumorigenesis, differentiation, and adhesion and thus clinicians should be aware of their existence. Adamantios Michalinos, Anastasia Constantinidou, and Michael Kontos Copyright © 2015 Adamantios Michalinos et al. All rights reserved. Clinical and Oncological Value of Preoperative BMI in Gastric Cancer Patients: A Single Center Experience Tue, 10 Feb 2015 12:03:30 +0000 Introduction. The impact of preoperative BMI on surgical outcomes and long-term survival of gastric cancer patients was investigated in various reports with contrasting results. Materials & Methods. A total of 378 patients who underwent a surgical resection for primary gastric cancer between 1994 and 2011 were retrospectively studied. Patients were stratified according to BMI into a normal group (<25, group A), an overweight group (25–30, group B), and an obesity group (≥30, group C). These 3 groups were compared according to clinical-pathological characteristics, surgical treatment, and long-term survival. Results. No significant correlations between BMI and TNM (2010), UICC stage (2010), Lauren’s histological type, surgical results, lymph node dissection, and postoperative morbidity and mortality were observed. Factors related to higher BMI were male gender , diabetes , and serum blood proteins . A trend to fewer lymph nodes retrieved during gastrectomy with lymphadenectomy in overweight patients (B and C groups) was observed, although not statistically significant. There was no difference in overall survival or disease-specific survival between the three groups. Conclusion. According to our data, BMI should not be considered a significant predictor of postoperative complications or long-term result in gastric cancer patients. Costantino Voglino, Giulio Di Mare, Francesco Ferrara, Lorenzo De Franco, Franco Roviello, and Daniele Marrelli Copyright © 2015 Costantino Voglino et al. All rights reserved. Endoplasmic Reticulum Stress in Intestinal Epithelial Cell Function and Inflammatory Bowel Disease Tue, 10 Feb 2015 07:43:02 +0000 In eukaryotic cells, perturbation of protein folding homeostasis in the endoplasmic reticulum (ER) causes accumulation of unfolded and misfolded proteins in the ER lumen, which activates intracellular signaling pathways termed the unfolded protein response (UPR). Recent studies have linked ER stress and the UPR to inflammatory bowel disease (IBD). The microenvironment of the ER is affected by a myriad of intestinal luminal molecules, implicating ER stress and the UPR in proper maintenance of intestinal homeostasis. Several intestinal cell populations, including Paneth and goblet cells, require robust ER function for protein folding, maturation, and secretion. Prolonged ER stress and impaired UPR signaling may cause IBD through: (1) induction of intestinal epithelial cell apoptosis, (2) disruption of mucosal barrier function, and (3) induction of the proinflammatory response in the gut. Based on our increased understanding of ER stress in IBD, new pharmacological approaches can be developed to improve intestinal homeostasis by targeting ER protein-folding in the intestinal epithelial cells (IECs). Katherine Luo and Stewart Siyan Cao Copyright © 2015 Katherine Luo and Stewart Siyan Cao. All rights reserved. Association between Virulence Factors and TRAF1/4-1BB/Bcl-xL Expression in Gastric Mucosa Infected with Helicobacter pylori Sun, 08 Feb 2015 10:07:57 +0000 Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor–associated factor 1 (TRAF1), tumor necrosis factor receptor superfamily member 9 (4-1BB), and B-cell lymphoma-extra large (Bcl-xL) in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG) patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM) patients, and 28 gastric carcinoma (Ca) patients. The expression of  TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients ( compared with CG). There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (). Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; ). Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue. Fen Wang, Xiang Wu, Zhiying Liu, Guangkui Bu, Xiayu Li, Nanfang Qu, Jin Peng, Canxia Xu, Shourong Shen, and Yi Yuan Copyright © 2015 Fen Wang et al. All rights reserved. Altered Chemokine Signalling in Endothelial Progenitor Cells from Acute Ulcerative Colitis Patients Sun, 08 Feb 2015 09:39:33 +0000 Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease, characterized by alternating stages of clinically active and inactive disease. UC exhibits several inflammatory characteristics, including immune activation, leukocyte infiltration, and altered vascular density. In UC, many of the upregulated inflammatory cytokines are proangiogenic and are released by diverse cell populations, such as infiltrating immune cells and endothelial cells (EC). Increasing evidences suggest that neovascularisation may involve also endothelial progenitor cells (EPCs). In this study we evaluated EPCs recruitment and homing, assessed by CXCR4 expression, in both acute and remitting phase of UC. We report an overall decrease of EPCs in UC patients (controls = 97,94 ± 37,34 cells/mL; acute = 31,10 ± 25,38 cells/mL; remitting = 30,33 ± 19,02 cells/mL; for both UC groups versus controls). Moreover CXCR4+-EPCs, committed to home in inflammatory conditions, were found to be reduced in acute UC patients compared to both remitting patients and controls (acute = 3,13 ± 4,61 cells/mL; controls = 20,12 ± 14,0; remitting = 19,47 ± 12,83; ). Interestingly, we found that administration of anti-inflammatory drugs in acute UC is associated with an increase in circulating EPCs, suggesting that this therapy may exert a strong influence on the progenitor cells response to inflammatory processes. L. De Toni, A. Di Nisio, S. Magagna, A. Michielan, M. Martinato, G. C. Sturniolo, R. D’Incà, C. Foresta, and A. Garolla Copyright © 2015 L. De Toni et al. All rights reserved. Toll-Like Receptor-1 and Receptor-2 and Beta-Defensin in Postcholecystectomy Bile Duct Injury Sun, 08 Feb 2015 06:22:19 +0000 Postcholecystectomy bile duct injuries (BDI) produce hepatic cholestasis and cause infection of the biliary tract. The biliary cells participate in secreting cytokines and in expression of immune response receptors. Toll-like receptors (TLRs) conduct signalling and activate the innate and adaptive inflammatory response. The objective was to determine the serum levels of TLR-2 and the expression of TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients. A transverse, analytical study with 2 groups was done. One group included healthy volunteers (control group) and other included 25 postcholecystectomy BDI patients with complete biliary obstruction. Using the Enzyme-linked Immunosorbent Assay (ELISA) technique, serum levels of TLR-2 were determined, and with immunofluorescence the morphologic analysis of TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients was performed. The average TLR-2 serum level in the control group was 0.0 pg/mL and in the BDI group,  pg/mL , bilateral Mann Whitney U). Immunofluorescence was used to determine the expression in liver biopsies, blood vessels, bile ducts, and hepatic parenchyma where 12 hepatic biopsies were positive for TLR-1 with average of  μm2; and 7 biopsies were positive for β-defensin with an average of  μm2; and 6 biopsies positive for TLR-2, obtaining an average of  μm2. In conclusion, TLR-1 and TLR-2 and β-defensin play an important role in the innate antimicrobial defense of the hepatobiliary system. Alejandra Guillermina Miranda-Díaz, José Manuel Hermosillo-Sandoval, Martha Arisbeth Villanueva-Pérez, Luis Miguel Román-Pintos, Trinidad García-Iglesias, Adolfo Daniel Rodríguez-Carrizalez, and Ernesto Germán Cardona-Muñoz Copyright © 2015 Alejandra Guillermina Miranda-Díaz et al. All rights reserved. Brand Name and Generic Proton Pump Inhibitor Prescriptions in the United States: Insights from the National Ambulatory Medical Care Survey (2006–2010) Thu, 05 Feb 2015 07:01:39 +0000 Introduction. Proton pump inhibitors (PPI) are one of the most commonly prescribed medication classes with similar efficacy between brand name and generic PPI formulations. Aims. We determined demographic, clinical, and practice characteristics associated with brand name PPI prescriptions at ambulatory care visits in the United States. Methods. Observational cross sectional analysis using the National Ambulatory Medical Care Survey (NAMCS) of all adult (18 yrs of age) ambulatory care visits from 2006 to 2010. PPI prescriptions were identified by using the drug entry code as brand name only or generic available formulations. Descriptive statistics were reported in terms of unweighted patient visits and proportions of encounters with brand name PPI prescriptions. Global chi-square tests were used to compare visits with brand name PPI prescriptions versus generic PPI prescriptions for each measure. Poisson regression was used to determine the incidence rate ratio (IRR) for generic versus brand PPI prescribing. Results. A PPI was prescribed at 269.7 million adult ambulatory visits, based on 9,677 unweighted visits, of which 53% were brand name only prescriptions. In 2006, 76.0% of all PPI prescriptions had a brand name only formulation compared to 31.6% of PPI prescriptions in 2010. Visits by patients aged 25–44 years had the greatest proportion of brand name PPI formulations (57.9%). Academic medical centers and physician-owned practices had the greatest proportion of visits with brand name PPI prescriptions (58.9% and 55.6% of visits with a PPI prescription, resp.). There were no significant differences in terms of median income, patient insurance type, or metropolitan status when comparing the proportion of visits with brand name versus generic PPI prescriptions. Poisson regression results showed that practice ownership type was most strongly associated with the likelihood of receiving a brand name PPI over the entire study period. Compared to HMO visits, patient visits at academic medical centers (IRR 4.2, 95% CI 2.2–8.0), physician-owned practices (IRR 3.9, 95% CI 2.1–7.1), and community health centers (IRR 3.6, 95% CI 1.9–6.6) were all more likely to have brand name PPIs. Conclusion. PPI prescriptions with brand name only formulations are most strongly associated with physician practice type. Andrew J. Gawron, Joseph Feinglass, John E. Pandolfino, Bruce K. Tan, Michiel J. Bove, and Stephanie Shintani-Smith Copyright © 2015 Andrew J. Gawron et al. All rights reserved. Early or Delayed Intervention for Bile Duct Injuries following Laparoscopic Cholecystectomy? A Dilemma Looking for an Answer Mon, 02 Feb 2015 10:00:25 +0000 Background. To evaluate the effect of timing of management and intervention on outcomes of bile duct injury. Materials and Methods. We retrospectively analyzed 92 patients between 1991 and 2011. Data concerned patient’s demographic characteristics, type of injury (according to Strasberg classification), time to referral, diagnostic procedures, timing of surgical management, and final outcome. The endpoint was the comparison of postoperative morbidity (stricture, recurrent cholangitis, required interventions/dilations, and redo reconstruction) and mortality between early (less than 2 weeks) and late (over 12 weeks) surgical reconstruction. Results. Three patients were treated conservatively, two patients were treated with percutaneous drainage, and 13 patients underwent PTC or ERCP. In total 74 patients were operated on in our unit. 58 of them underwent surgical reconstruction by end-to-side Roux-en-Y hepaticojejunostomy, 11 underwent primary bile duct repair, and the remaining 5 underwent more complex procedures. Of the 56 patients, 34 patients were submitted to early reconstruction, while 22 patients were submitted to late reconstruction. After a median follow-up of 93 months, there were two deaths associated with BDI after LC. Outcomes after early repairs were equal to outcomes after late repairs when performed by specialists. Conclusions. Early repair after BDI results in equal outcomes compared with late repair. BDI patients should be referred to centers of expertise and experience. Evangelos Felekouras, Athanasios Petrou, Kyriakos Neofytou, Demetrios Moris, Nikolaos Dimitrokallis, Konstantinos Bramis, John Griniatsos, Emmanouil Pikoulis, and Theodoros Diamantis Copyright © 2015 Evangelos Felekouras et al. All rights reserved. Psychological Therapies in Patients with Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Sat, 31 Jan 2015 08:09:43 +0000 Background. Irritable bowel syndrome (IBS) is a poorly understood disease with few effective treatments. Psychosocial factors are believed to contribute to the pathogenesis of IBS. Objective. To evaluate the evidence for psychological therapies in IBS treatment. Methods. We searched six medical databases through February 6, 2014, for randomized controlled trials (RCTs) of psychological therapies for the treatment of IBS. Two independent reviewers identified the RCTs, extracted the data, and assessed trial quality. We used the random-effect model to pool standardized mean difference (SMD) and 95% confidence interval (CI) across trials. Results. 15 RCTs that mostly evaluated cognitive behavioral therapy were included. Psychological therapies were associated with improvement in IBS symptoms severity scales (SMD −0.618; 95% CI: −0.853 to −0.383), IBS-Quality of Life (SMD 0.604; 95% CI: 0.440 to 0.768), and abdominal pain (SMD −0.282; 95% CI: −0.562 to −0.001). No statistically significant effect was observed on diarrhea or constipation. Limitations. The trials were at increased risk of bias and the overall sample size was small leading to imprecision. Conclusion. Psychological therapies may improve the quality of life and symptom severity in IBS. The effect size noted is moderate to large and is clinically meaningful. Osama Altayar, Varun Sharma, Larry J. Prokop, Amit Sood, and Mohammad Hassan Murad Copyright © 2015 Osama Altayar et al. All rights reserved. Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy Thu, 29 Jan 2015 09:30:08 +0000 Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis) who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116). In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90–0.99, ) and total serum cholesterol (OR: 1.02, 95% CI: 1.01–1.04, ) were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94–0.99, ) was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis. Chang Seok Bang, Yong Sub Lee, Jai Hoon Yoon, Youn Jeong Kim, Jin Bong Kim, and Dong Joon Kim Copyright © 2015 Chang Seok Bang et al. All rights reserved. Submucosal Injection Solution for Endoscopic Resection in Gastrointestinal Tract: A Traditional and Network Meta-Analysis Thu, 29 Jan 2015 07:10:30 +0000 Objective. To explore and define the current optimal submucosal injection solution used in ESD and EMR for gastrointestinal tract neoplasms in terms of clinical outcomes and other aspects. Methods. PubMed, Cochrane Library, Embase, and clinical trials register center were searched with terms of “endoscopic resection” and “submucosal injection solution” to identify relevant randomized controlled trials (RCTs). Both direct comparison using traditional meta-analysis method and indirect comparison using network meta-analysis method were performed. Results. A total of 11 RCTs with 1152 patients were included. Meta-analysis showed that, compared with normal saline, other submucosal injection solutions induced a significant increase in terms of en bloc resection rate %, OR = 2.11, 95% CI (1.36, 3.26), and and complete resection rate %, OR = 2.14, 95% CI (1.41, 3.24), and ; and there was no significant difference in the incidence of total complications %, OR = 0.87, 95% CI (0.59, 1.29), and . Conclusions. Other newly developed submucosal injection solutions significantly increased en bloc resection rate and complete resection rate and decreased bleeding rate and finical cost of endoscopic resection in gastrointestinal tract, while current evidence did not find the difference between them, which need to be explored by further studies. Zhang Yu Huai, Wei Feng Xian, Luo Chang Jiang, and Wang Xi Chen Copyright © 2015 Zhang Yu Huai et al. All rights reserved. Duodenal Aspirates for Small Intestine Bacterial Overgrowth: Yield, PPIs, and Outcomes after Treatment at a Tertiary Academic Medical Center Wed, 28 Jan 2015 14:34:43 +0000 Duodenal aspirates are not commonly collected, but they can be easily used in detection of small intestinal bacterial overgrowth (SIBO). Proton pump inhibitor (PPI) use has been proposed to contribute to the development of SIBO. We aimed to determine the yield of SIBO-positive cultures detected in duodenal aspirates, the relationship between SIBO and PPI use, and the clinical outcomes of patients identified by this method. In a retrospective study, we analyzed electronic medical records from 1263 consecutive patients undergoing upper endoscopy at a tertiary medical center. Aspirates were collected thought out the third and fourth portions of the duodenum, and cultures were considered to be positive for SIBO if they produced more than 100,000 cfu/mL. Culture analysis of duodenal aspirates identified SIBO in one-third of patients. A significantly higher percentage of patients with SIBO use PPIs than patients without SIBO, indicating a possible association. Similar proportions of patients with SIBO improved whether or not they received antibiotic treatment, calling into question the use of this expensive therapy for this disorder. Diana L. Franco, Molly B. Disbrow, Allon Kahn, Laura M. Koepke, Lucinda A. Harris, M. Edwyn Harrison, Michael D. Crowell, and Francisco C. Ramirez Copyright © 2015 Diana L. Franco et al. All rights reserved.