March 2008

Volume 134Issue 3p649-900, e1-e20

This Month in Gastroenterology

  • This Month in Gastroenterology

    • Jan Tack,
    • John M. Carethers
    Published in issue: March 2008
    A number of technical advances, aiming at better detection of (pre-)malignant lesions at endoscopy have emerged over the last few years. Chromoendoscopy is a technique in which staining agents (indigo carmine or acetic acid) are sprayed on the mucosal surface of the gastrointestinal tract to enhance the endoscopic evaluation of the mucosa. It is usually combined with magnifying endoscopy to obtain optimal visualization of arrangements of the mucosal pit patterns associated with (pre-)malignant lesions.

Gastroenterology and Hepatology News

  • Genomics-Based Medicine May Drive Health Care Reform

    • Les Lang
    Published in issue: March 2008
    Calls for health care reform in the United States rest largely on issues related to the insured and underinsured. According to Dr James P. Evans, Professor of Genetics and Medicine at the University of North Carolina at Chapel Hill School of Medicine, a transformation in patient care will come from the emergence of new technology borne of new knowledge. He says it is the advent of individualized medicine driven by advances in genomics that will add to widespread demands for universal health coverage as more individuals stand to benefit from genetically targeted care.
  • FDA Approves First Quick Test for Drug-Resistant Staphylococcus Infections

    • Les Lang
    Published in issue: March 2008
    The US Food and Drug Administration (FDA) announced in January 2008 that it had cleared for marketing the first rapid blood test for the drug-resistant bacterium known as MRSA (methicillin-resistant Staphylococcus aureus), which can cause potentially fatal infections. The test identifies the presence of MRSA in 2 hours (Figure 1).
  • Americans Rate Health Care a Top Issue for Candidates to Discuss

    • Les Lang
    Published in issue: March 2008
    Iraq and health care are the top 2 issues that the public wants to hear presidential candidates discuss, according to the Kaiser Health Tracking Poll: Election 2008 conducted in December 2007. More than one third (35%) of respondents named the war as the top issue with health care (30%) ranking second, followed by the economy (21%) and immigration (17%).
  • Expression Patterns of MicroRNAs Appear Altered in Colon Cancer and Are Associated With Poor Outcomes

    • Les Lang
    Published in issue: March 2008
    Preliminary research has found an association between certain microRNA expression patterns and poor survival and treatment outcomes for colon cancer, according to a study in the January 30, 2008, issue of the Journal of the American Medical Association. “Even though 5-year mortality rates have modestly declined over the last 3 decades, there is still a need to identify new prognostic biomarkers and therapeutic targets for this disease,” the authors write. They add that microRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer.


  • Medical Education: A Key Partner in Realizing Personalized Medicine in Gastroenterology

    • Kalpesh K. Patel,
    • Mark W. Babyatsky
    Published in issue: March 2008
    Completion of the human genome sequence heralds an era that utilizes the “individual patient’s genome [to] help determine the optimal approach to care, whether it is preventive, diagnostic, or therapeutic,”1 defining personalized medicine broadly to provide biomarkers for disease prevention and treatment, new targets for drug development, and tools to make drugs safer and more efficacious. Limitations to personalized medicine include genetic testing availability, cost, insurance coverage, ethical concerns, scientific progress, and evidence of clinical usefulness; education in these areas may help to bridge a growing knowledge gap between science and practitioners.

Biographical Sketch

  • Paneth of Paneth Cells

    • William S. Haubrich
    Published in issue: March 2008
    Josef Paneth (1857–1890) was an Austrian physician who held academic chairs in physiology at Breslau and Vienna. In 1888, he described the unique epithelial cells that contain large secretory granules and occupy the fundus of the glands of Lieberkühn. Decades later, the true function of these cells was recognized—namely, to provide host defense against invasion by potentially harmful intestinal microbes. Afield of physiology, Paneth engaged in intense discussions with Sigmund Freud (1856–1939) in psychiatry and with Friedrich Nietzsche (1844–1900) in philosophy.

Comment From the Editors

  • Genetic Association Studies: From “Searching Under the Lamppost” to “Fishing in the Pond”

    • Hashem B. El-Serag,
    • Donna L. White,
    • Nandita Mitra
    Published in issue: March 2008
    In recent years, a major focus of research in gastroenterology and hepatology has been identification of genetic determinants of disease. There are now numerous reports of widely accepted associations between heritable genetic variants and several common complex digestive disorders including Crohn’s disease and colon cancer. Scientific and technical advances, such as completion of the Human Genome and HapMap Projects, development of high-throughput techniques, and a dramatic reduction in the cost of genetic testing have resulted in an explosion of genetic research.

Imaging and Advanced Technology

  • Implantable Gastric Electrical Stimulation: Ready for Prime Time?

    • Jieyun Yin,
    • Jiande D.Z. Chen
    Published in issue: March 2008
    Electrical stimulation has been widely applied in various clinical areas: from cardiac pacemakers to implantable defibrillators and from spinal cord stimulation to deep brain stimulation. The technology has evolved from external large pacemakers to implantable pin-size pulse generators. In contrast, electrical stimulation of the gut has lagged far behind cardiac pacing or electrical nerve stimulation. Although gastric electrical stimulation (GES) was first introduced >40 years ago,1 little progress was made until recent years.

Clinical Challenges and Images in GI

  • Clinical Challenges and Images in GI

    • Richard Kellermayer,
    • Ajay K. Jain,
    • George Ferry,
    • Marietta M. Deguzman,
    • R. Paul Guillerman
    Published in issue: March 2008
    Question: A 17-year-old girl with a 5-year history of colonic Crohn’s disease presented with a 5-day history of worsening nausea, emesis, and decreased oral intake. Since her initial diagnosis, she had been treated with mesalamine and short courses of corticosteroids for 2 years then initiated on 6-mercaptopurine therapy. Over the next 3 years, she was not compliant and frequently required steroid therapy. Seven months before this presentation, she was started on intravenous infliximab (5 mg/kg) and maintained on infusions about every 6 weeks in remission and free of symptoms.
  • Clinical Challenges and Images in GI

    • Najat Mourra,
    • Maïté Lewin,
    • Yann Parc
    Published in issue: March 2008
    Question: A previously healthy 22-year-old man presented with recent dysphagia and fever. On endoscopic examination, a small mucosal defect was found 26 cm from the incisor teeth, with narrow lumen. Contrast-enhanced computed tomography (CT) with esophagogastric opacification was performed (Figure 1A), as well as an esophagogram (Figure 1B).

Electronic Clinical Challenges and Images in GI

  • Electronic Clinical Challenges and Images in GI

    • Jan J. Koornstra,
    • Jan H. Kleibeuker
    Published in issue: March 2008
    Question: A 75-year-old woman presented with 3-week history of jaundice and a painless, bile-producing skin defect in the right upper abdominal quadrant (Figure 1A). No previous trauma, puncture, or surgery was reported. She had no fever. Laboratory parameters showed abnormal liver chemistry tests: aspartate aminotransferase, 74; alanine aminotransferase, 67; alkaline phosphatase, 360; γ-glutamyltransferase, 252; total bilirubin, 10.4 mg/dL; and conjugated bilirubin, 7.9 mg/dL. Abdominal computed tomography (CT) was performed (Figure 1B).
    Online Only
  • Electronic Clinical Challenges and Images in GI

    • Fernando Maria de Benedictis,
    • Stefano Nobile,
    • Ivano Lorenzini
    Published in issue: March 2008
    Question: A 12-year-old girl presented with a 6-month history of weight loss and recurrent abdominal pain. The patient denied any fever, nausea, vomiting, and diarrhea. Physical examination revealed mild tenderness in the right lower quadrant. Laboratory values were within the normal limits except for mild anemia (hemoglobin, 9.6 g/dL; iron, 12 μg/dL; transferrin, 152 mg/dL; and ferritin, 85 ng/mL), reduced serum albumin (2.8 g/dL), and increased erythrocyte sedimentation rate (78 mm/h). Tuberculin PPD test was positive.
    Online Only

Clinical- Alimentary Tract

  • Chromoendoscopy and Narrow-Band Imaging Compared With High-Resolution Magnification Endoscopy in Barrett’s Esophagus

    • Wouter Curvers,
    • Lubbertus Baak,
    • Ralf Kiesslich,
    • ...
    • Fiebo Ten Kate,
    • Paul Fockens,
    • Jacques Bergman
    Published online: January 11, 2008
    Background & Aims: The aim of this study was to compare magnified still images obtained with high-resolution white light endoscopy, indigo carmine chromoendoscopy, acetic acid chromoendoscopy, and narrow-band imaging to determine the best technique for use in Barrett’s esophagus. Methods: We obtained magnified images from 22 areas with the 4 aforementioned techniques. Seven endoscopists with no specific expertise in Barrett’s esophagus or advanced imaging techniques and 5 international experts in this field evaluated these 22 areas for overall image quality, mucosal image quality, and vascular image quality.
    Linking Article with CGHCME Quiz
  • Impact of Hospital Volume on Postoperative Morbidity and Mortality Following a Colectomy for Ulcerative Colitis

    • Gilaad G. Kaplan,
    • Ellen P. McCarthy,
    • John Z. Ayanian,
    • Joshua Korzenik,
    • Richard Hodin,
    • Bruce E. Sands
    Published online: January 11, 2008
    Background & Aims: Postoperative morbidity and mortality following a colectomy for ulcerative colitis (UC) has been primarily reported from tertiary care referral centers that perform a high volume of operations; however, the postoperative outcomes among nonselected hospitals are not known. We set out to evaluate postoperative morbidity and mortality using a nationally representative database and to determine the factors that influenced outcomes. Methods: We analyzed the 1995–2005 Nationwide Inpatient Sample to identify 7108 discharges for UC patients who underwent a total abdominal colectomy.
    Online ExtraAdditional Online Content Available
  • Rosiglitazone for Active Ulcerative Colitis: A Randomized Placebo-Controlled Trial

    • James D. Lewis,
    • Gary R. Lichtenstein,
    • Julius J. Deren,
    • ...
    • Lisa Nessel,
    • Gary D. Wu
    • Rosiglitazone for Ulcerative Colitis Study Group
    Published online: December 07, 2007
    Background & Aims: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARγ), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC). Methods: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC.
    CME QuizAdditional Online Content Available
  • The Effect of Auditory Stress on Perception of Intraesophageal Acid in Patients With Gastroesophageal Reflux Disease

    • Ronnie Fass,
    • Bruce D. Naliboff,
    • Shira S. Fass,
    • ...
    • Christopher Wendel,
    • Isaac B. Malagon,
    • Emeran A. Mayer
    Published online: December 07, 2007
    Background & Aims: Most patients with gastroesophageal reflux disease (GERD) report that stress exacerbates their symptoms, yet mechanisms underlying this association remain unknown. We sought to determine the effect of an acute laboratory stressor on perceptual and emotional responses to intraesophageal acid perfusion in healthy controls and patients with GERD. Methods: Forty-six patients with heartburn and 10 healthy controls underwent upper endoscopy and, if negative, pH monitoring. Assessment of psychologic factors and health-related quality of life was done by a questionnaire.

Clinical - Liver, Pancreas, and Biliary Tract

  • Immunoglobulin G4–Associated Cholangitis: Clinical Profile and Response to Therapy

    • Amaar Ghazale,
    • Suresh T. Chari,
    • Lizhi Zhang,
    • ...
    • Santhi Swaroop Vege,
    • Keith Lindor,
    • Michael B. Farnell
    Published online: December 07, 2007
    Background & Aims: Immunoglobulin (Ig)G4-associated cholangitis (IAC) is the biliary manifestation of a steroid-responsive multisystem fibroinflammatory disorder in which affected organs have a characteristic lymphoplasmacytic infiltrate rich in IgG4-positive cells. We describe clinical features, treatment response, and predictors of relapse in IAC and compare relapse rates in IAC with intrapancreatic vs proximal bile duct strictures. Methods: We reviewed clinical, serologic, and imaging characteristics and treatment response in 53 IAC patients.
    Linking Article with CGH
  • Regulatory Polymorphisms in the Promoter of CXCL10 Gene and Disease Progression in Male Hepatitis B Virus Carriers

    • Guohong Deng,
    • Gangqiao Zhou,
    • Rong Zhang,
    • ...
    • Boqing Qiang,
    • Yuming Wang,
    • Fuchu He
    Published online: January 03, 2008
    Background & Aims: The importance of expression of interferon gamma–inducible protein of 10 kilodaltons (IP-10, CXCL10) during chronic hepatitis B virus (HBV) infection has been recently emphasized. In this report, we investigated whether the naturally occurred sequence variations in the CXCL10 gene impact liver damage and disease progression of chronic HBV infection. Methods: A hospital-based case-control study was conducted, and a total of 613 and 1787 unrelated Han Chinese HBV carriers were recruited from Beijing and Chongqing, respectively.
    Online ExtraLinking Article with CGHAdditional Online Content Available
  • Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

    • Simon Mwangi,
    • Mallappa Anitha,
    • Chaithanya Mallikarjun,
    • ...
    • Shanthi V. Sitaraman,
    • Frank Anania,
    • Shanthi Srinivasan
    Published online: January 03, 2008
    Background & Aims: Pancreatic β-cell mass increases in response to increased demand for insulin, but the factors involved are largely unknown. Glial cell line-derived neurotrophic factor (GDNF) is a growth factor that plays a role in the development and survival of the enteric nervous system. We investigated the role of GDNF in regulating β-cell survival. Methods: Studies were performed using the β-TC-6 pancreatic β-cell line, isolated mouse pancreatic β cells, and in vivo in transgenic mice that overexpress GDNF in pancreatic glia.

Basic - Alimentary Tract

  • Combined Functional and Positional Gene Information for the Identification of Susceptibility Variants in Celiac Disease

    • Ainara Castellanos–Rubio,
    • Ainhoa Martin–Pagola,
    • Izortze Santín,
    • ...
    • Luis Castaño,
    • Juan Carlos Vitoria,
    • Jose Ramon Bilbao
    Published online: November 29, 2007
    Background & Aims: Celiac disease is a complex, immune-mediated disorder of the intestinal mucosa with a strong genetic component. HLA-DQ2 is the major determinant of risk, but other minor genes, still to be identified, also are involved. Methods: We designed a strategy that combines gene expression profiling of intestinal biopsy specimens, linkage region information, and different bioinformatics tools for the selection of potentially regulatory single-nucleotide polymorphisms (SNPs) involved in the disease.
    Additional Online Content AvailableEditorial Accompanies Article
  • Substance P as a Novel Anti-obesity Target

    • Iordanes Karagiannides,
    • Daniel Torres,
    • Yu–Hua Tseng,
    • ...
    • Daniel Espinoza,
    • Charalabos Pothoulakis,
    • Efi Kokkotou
    Published online: January 03, 2008
    Background & Aims: Substance P (SP) is an 11-amino acid peptide that belongs to the tachykinin family of peptides. SP acts in the brain and in the periphery as a neuropeptide, neurotransmitter, and hormone affecting diverse physiologic pathways, mainly via its high-affinity neurokinin-1 receptor (NK-1R). Its presence in the hypothalamus and other areas of the brain that regulate feeding as well as in the stomach and small intestine prompted us to investigate its role on appetite control and energy balance.
    Online ExtraAdditional Online Content Available
  • Hypoxia-Independent Activation of HIF-1 by Enterobacteriaceae and Their Siderophores

    • Hanna Hartmann,
    • Holger K. Eltzschig,
    • Helena Wurz,
    • ...
    • Diana Neumann,
    • Sean P. Colgan,
    • Volkhard A.J. Kempf
    Published online: December 07, 2007
    Background & Aims: Hypoxia inducible factor-1 (HIF-1) is the key transcriptional regulator during adaptation to hypoxia. Recent studies provide evidence for HIF-1 activation during bacterial infections. However, molecular details of how bacteria activate HIF-1 remain unclear. Here, we pursued the role of bacterial siderophores in HIF-1 activation during infection with Enterobacteriaceae. Methods: In vivo, HIF-1 activation and HIF-1-dependent gene induction in Peyer’s patches were analyzed after orogastric infection with Yersinia enterocolitica.
    Online ExtraAdditional Online Content Available
  • Chronic Enteric Salmonella Infection in Mice Leads to Severe and Persistent Intestinal Fibrosis

    • Guntram A. Grassl,
    • Yanet Valdez,
    • Kirk S.B. Bergstrom,
    • Bruce A. Vallance,
    • B. Brett Finlay
    Published online: January 10, 2008
    Background & Aims: Intestinal fibrosis and stricture formation are serious complications of Crohn’s disease, often requiring surgical intervention. Unfortunately, the mechanisms underlying intestinal fibrosis development are poorly understood, in part because of the lack of relevant animal models. Here, we present a novel murine model of severe and persistent intestinal fibrosis caused by chronic bacterial-induced colitis. Methods: Mice were treated with streptomycin 24 hours prior to oral infection with Salmonella enterica serovar Typhimurium.
    Online ExtraAdditional Online Content AvailableEditorial Accompanies Article

Basic - Liver, Pancreas, and Biliary Tract

  • Continuous Cell Injury Promotes Hepatic Tumorigenesis in Cdc42-Deficient Mouse Liver

    • Jolanda van Hengel,
    • Petra D’Hooge,
    • Bart Hooghe,
    • ...
    • Martina Klempt,
    • Cord Brakebusch,
    • Frans van Roy
    Published online: January 10, 2008
    Background & Aims: The Rho small guanosine triphosphatase Cdc42 is critical for diverse cellular functions, including regulation of actin organization, cell polarity, intracellular membrane trafficking, transcription, cell-cycle progression, and cell transformation. This implies that Cdc42 might be required for liver function. Methods: Mice in which Cdc42 was ablated in hepatocytes and bile duct cells were generated by Cre-loxP technology. Livers were examined by histologic, immunohistochemical, ultrastructural, and serum analysis to define the effect of loss of Cdc42 on liver structure.
    Additional Online Content AvailableEditorial Accompanies Article
  • Epigenetic Inhibition of Nuclear Receptor Small Heterodimer Partner Is Associated With and Regulates Hepatocellular Carcinoma Growth

    • Nan He,
    • Kyungtae Park,
    • Yuxia Zhang,
    • Jiansheng Huang,
    • Shan Lu,
    • Li Wang
    Published online: January 11, 2008
    Background & Aims: Aberrant hypermethylation of promoter regions in cytosine-guanine dinucleotides (CpG) islands has been shown to be associated with transcriptional silencing of tumor-suppressor genes in many cancers. This study evaluated the methylation profile and the tumor-suppressive function of the small heterodimer partner (SHP, NR0B2) in the development of human hepatocellular carcinoma (HCC). Methods: Human HCC pathologic specimens and cell lines were used as model systems in this study.
    Additional Online Content Available
  • HIV Increases HCV Replication in a TGF-β1–Dependent Manner

    • Wenyu Lin,
    • Ethan M. Weinberg,
    • Andrew W. Tai,
    • ...
    • Carolina B. Borges,
    • Run–Xuan Shao,
    • Raymond T. Chung
    Published online: January 11, 2008
    Background & Aims: Human immunodeficiency virus (HIV) coinfection increases hepatitis C virus (HCV)-related progression of hepatic fibrosis, increases HCV persistence, and decreases response rates to interferon-based anti-HCV therapy. It has remained unclear how HIV, a nonhepatotropic virus, accelerates the progression of liver disease by HCV. Methods: We explored the possibility that circulating HIV and/or its proteins contribute to the pathogenesis of HCV through engagement of extracellular coreceptors on hepatocytes.
    Additional Online Content Available
  • Hepatitis C Virus Replicates in the Same Immune Cell Subsets in Chronic Hepatitis C and Occult Infection

    • Tram N.Q. Pham,
    • Dawn King,
    • Sonya A. MacParland,
    • ...
    • S. Bharati Reddy,
    • Ford R. Bursey,
    • Tomasz I. Michalak
    Published online: December 13, 2007
    Background & Aims: Infection of the lymphatic system by hepatitis C virus (HCV) appears to be an intrinsic characteristic of chronic hepatitis C (CHC) and low-level (occult) HCV infection, but the subsets of immune cells involved were not defined. The aim of this study was to characterize HCV replication status and to assess virus compartmentalization in CD4+ and CD8+ T lymphocytes, B cells, and monocytes in CHC, and silent infection persisting after resolution of hepatitis C. Methods: Immune cell subtypes isolated from 7 patients with CHC and 7 individuals with occult infection were analyzed for HCV-RNA–positive and –negative strands and, in selected cases, nonstructural protein 5A display and HCV variants.
    Additional Online Content Available
  • Purification of Fetal Liver Stem/Progenitor Cells Containing all the Repopulation Potential for Normal Adult Rat Liver

    • Michael Oertel,
    • Anuradha Menthena,
    • Yuan–Qing Chen,
    • Børge Teisner,
    • Charlotte Harken Jensen,
    • David A. Shafritz
    Published online: January 11, 2008
    Background & Aims: Previously, we showed high-level, long-term liver replacement after transplantation of unfractionated embryonic day (ED) 14 fetal liver stem/progenitor cells (FLSPC). However, for clinical applications, it will be essential to transplant highly enriched cells, while maintaining high repopulation potential. Methods: Dlk-1, a member of the δ-like family of cell surface transmembrane proteins, is highly expressed in human and rodent fetal liver. Dlk-1+ cells, isolated from ED14 fetal liver using immunomagnetic beads, were examined for their hepatic gene expression profile and characteristic properties in vitro and their proliferative and differentiation potential in vivo after transplantation into normal adult rat liver.
    Additional Online Content Available
  • Native Umbilical Cord Matrix Stem Cells Express Hepatic Markers and Differentiate Into Hepatocyte-like Cells

    • David Campard,
    • Philippe A. Lysy,
    • Mustapha Najimi,
    • Etienne Marc Sokal
    Published online: January 03, 2008
    Background & Aims: Umbilical cord matrix stem cells (UCMSCs) are able to differentiate into mesodermal and ectodermal lineages. The present study investigates the differentiation potential of human UCMSCs into hepatic lineage. Methods: We isolated human UCMSCs and characterized them in vitro by measuring their expansion potential, by assessing expression of mesenchymal stem cell (MSC) markers, and by evaluating their ability to differentiate into adipocytes and osteocytes. UCMSCs were thereafter subjected to a hepatogenic differentiation protocol.
    Editorial Accompanies Article

Reviews in Basic and Clinical Gastroenterology

  • Current View: Intestinal Stem Cells and Signaling

    • David H. Scoville,
    • Toshiro Sato,
    • Xi C. He,
    • Linheng Li
    Published in issue: March 2008
    Studies using mice have yielded significant amounts of information regarding signaling pathways, such as Wnt, bone morphogenic protein, PtdIns(3,4,5) kinase, and Notch, involved in intestinal development and homeostasis, including stem cell regulation and lineage specification and maturation. However, attempts to model signals definitively that control intestinal stem cells have been difficult because of a long-standing and recently reenergized debate surrounding their location. Although crypt-based columnar cells have been recently shown to display self-renewal and multipotential capacity, a large body of evidence supports long-term label-retaining cells, located on average at the +4 position just above the Paneth cells, as putative stem cells.

Continuing Medical Education (CME) Activities


  • Hunting for Celiac Disease Genes

    • Ludvig M. Sollid
    Published in issue: March 2008
    Celiac disease results from a dysregulated immune response to dietary wheat gluten and related cereal proteins.1,2 The disease is an acquired disorder, but with a strong hereditary component. The evidence for the importance of genes comes from familial and twin studies. About 10% of first-degree relatives are affected by the disease, compared with the population prevalence of about 1%; the pairwise concordance rates in monozygotic and dizygotic twins are about 75% and 10%, respectively.3 Already in 1972 the association between celiac disease and the HLA locus had been established.
  • Using Salmonella enterica Serotype Typhimurium to Model Intestinal Fibrosis

    • Beth A. McCormick
    Published online: February 13, 2008
    Crohn’s disease (CD) and ulcerative colitis (UC) are life-long, relapsing illnesses that primarily affect the gastrointestinal tract of the young adult. Such conditions are characterized by chronic inflammation, mucosal damage, and epithelial cell destruction resulting from a complex interplay among genetic, immunologic, and microbial factors. Unlike UC, in which inflammation is limited to the mucosa, the inflammation that occurs during CD is transmural and granulomatous, and affects not only the intestinal mucosa but also the muscularis and serosa.
  • Rho GTPase and Wnt Signaling Pathways in Hepatocarcinogenesis

    • André Lechel,
    • Karl Lenhard Rudolph
    Published in issue: March 2008
    Rho GTPase and Wnt/β-catenin signaling pathways are interconnected and both pathways are frequently activated in human hepatocarcinogenesis. Rho GTPases and the Wnt/β-catenin pathway regulate multiple cellular processes, including cell polarity, proliferation, differentiation, and apoptosis. A functional role of Wnt/β-catenin activation in hepatocarcinogenesis has been demonstrated in genetic mouse models. In this issue of Gastroenterology, van Hengel et al1 provide first experimental evidence that hepatic deletion of the gene encoding the Rho GTPase—Cdc42—induces chronic liver damage and hepatocarcinogenesis in mice.
  • To Be or Not to Be: Generation of Hepatocytes From Cells Outside the Liver

    • Ira J. Fox,
    • Stephen C. Strom
    Published in issue: March 2008
    Stem cells hold great promise as a source of material for novel, minimally invasive therapies to treat a variety of neurodegenerative disorders, diabetes, heart disease, and numerous other debilitating conditions. It is hoped that stem cells derived from a variety of sources might also produce a plentiful supply of cells with characteristics identical to those of primary human hepatocytes.

Selected Summaries

  • GERD and Obesity: A Real BIG Issue!

    • Michael F. Vaezi
    Published in issue: March 2008
    El-Serag HB, Ergun GA, Pandolfino J, et al. (Section of Health Services, Houston Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas). Obesity increases oesophageal acid exposure. Gut 2007;56:749–755.
  • Gluten-Free Diets in Celiac Disease: Does Life Mean Life?

    • Nick M. Croft
    Published in issue: March 2008
    Matysiak-Budnik T, Malamut G, de Serre NP, et al. (INSERM, U793, Faculté de Médecine René Descartes, Paris, France). Long-term evaluation of 61 coeliac patients diagnosed in childhood: evolution towards latency is possible on a normal diet. Gut 2007;56:1379–1386.
  • Reply

    • Tamara Matysiak–Budnik,
    • Georgia Malamut,
    • Jacques Schmitz,
    • Christophe Cellier
    Published in issue: March 2008
    We thank Dr Croft for his comments and his interest in our study. However, some of the issues highlighted by Dr Croft deserve explanations.
  • Farm Animals and Inflammatory Bowel Disease: Old MacDonald Had Poor Hygiene

    • L. Campbell Levy,
    • Scott E. Plevy
    Published in issue: March 2008
    Radon K, Windstetter D, Poluda AL, et al. (Unit for Occupational and Environmental Epidemiology & NetTeaching, Institute and Outpatient Clinic for Occupational and Environmental Medicine, Munich, Germany). Contact with farm animals in early life and juvenile inflammatory bowel disease: a case-control study. Pediatrics 2007;120:354–361.
  • Reply

    • Katja Radon,
    • Doris Windstetter,
    • Anna Laura Poluda,
    • ...
    • Erika von Mutius,
    • Sibylle Koletzko
    • CAT-Study Team
    Published in issue: March 2008
    We are pleased by the precise review of our paper by Drs Levy and Plevy. Furthermore, we are delighted by the careful comparison between the results of our study and the case-control studies by Amre et al (Am J Gastroenterol 2006;101:1005–1011) and Bernstein et al (Am J Gastroenterol 2006;101:993–1002).
  • Molecular Information Defines a New Entity of Hereditary Colorectal Cancer

    • Rodrigo Jover,
    • Antoni Castells
    Published in issue: March 2008
    Valle L, Perea J, Carbonell P, et al. (Familial Cancer Unit, Spanish National Cancer Centre, Melchor Fernández Almagro, Madrid, Spain). Clinicopathologic and pedigree differences in Amsterdam I-positive Hereditary Nonpolyposis Colorectal Cancer families according to tumor microsatellite instability status. J Clin Oncol 2007;25:781–786.
  • Reply

    • Laura Valle,
    • Miguel Urioste
    Published in issue: March 2008
    In the recently published study “Clinicopathologic and pedigree differences in Amsterdam I-positive Hereditary Nonpolyposis Colorectal Cancer families according to tumor microsatellite status” (J Clin Oncol 2007;25:781–786), we showed clear differences between MSI and MSS Amsterdam I-positive families. These findings support and give a greater weight to the previous idea of the existence of a different hereditary colorectal cancer (CRC) syndrome, characterized by tumor MSS, normal inmunohistochemical MMR expression, exclusivity of colorectal tumors without mucin production, lack of multiple primary tumors, and higher age of onset.
  • Reply

    • Will L. Irving,
    • Brian J. Thomson,
    • Keith R. Neal
    Published in issue: March 2008
    Editor’s note: The following reply refers to the Summary, “Mortality in Patients With Hepatitis C” (Gastroenterology 2008;134:635–637).

Print and Media Reviews

    • Thomas Ullman,
    • Steven Itzkowitz
    Published in issue: March 2008
    Although our shelves often house them, clinical gastroenterologists seldom seek clinical information from a textbook. Particularly when it comes to complex clinical matters, even recently published textbooks lack current information, with chapters that were written months and sometimes years ahead of publication and content that may not be sufficiently relevant to individual patient concerns. Furthermore, in an Internet- and Google-lubricated world, textbooks lack the immediacy of the World Wide Web and harbor antiquated searching capabilities, with end-of-book indices laced with alphabetized entries often of 8-point or smaller fonts.
    • Luis Balart
    Published in issue: March 2008
    Reviewing the 10th edition of this classic textbook is a most difficult task for me. What do you say about the bible of clinical hepatology, first published in 1956 when most of us in the practice of gastroenterology and hepatology were either children or not even born yet? What about the three editors—Gene Schiff, Willis Maddrey, and Mike Sorrell—the grand masters of hepatology? Note that I did not say grand old men of Hepatology because, if you know these three, you know that each is as vibrant and active today as any young hepatologist out there and their contribution with this 10th edition is the proof of their continued mastery of the subject and their relevance in the modern age of hepatology.


  • The Peruvian Contribution to the Knowledge of the Role of Helicobacter pylori Infection in the Genesis of Gastric Premalignant Lesions That Predispose to Gastric Cancer

    • Raul Leon–Barua,
    • Sixto Recavarren–Arce,
    • Alberto Ramirez–Ramos,
    • Robert H. Gilman
    Published in issue: March 2008
    We read with interest the recently published review by Correa and Houghton1 on the “Carcinogenesis of Helicobacter pylori” and would like to present additional information that was omitted in the review. It has been kindly recognized that the first studies on the relationship between H pylori infection and gastric cancer were done by us in Peru.2
  • Biliary Injury After Laparoscopic Cholecystectomy: Why Still a Problem?

    • Travelyan Walker
    Published in issue: March 2008
    I read with great interest the article “Biliary Injury Following Laparoscopic Cholecystectomy: Why Still a Problem?” by Vollmer et al1 in the September 2007 issue of Gastroenterology. Throughout the article, the authors provide several thought-provoking explanations for why biliary injury during laparoscopic cholecystectomy remains a problem despite a maturing procedure and expected learning curve. Particularly intriguing is the depiction of 2 different scenarios of a surgeon who either overextends his laparoscopic experience during a challenging laparoscopic cholecystectomy case when disease warrants conversion to an open cholecystectomy subsequently leading to biliary injury and/or of the surgeon who due to inexperience fails to recognize the need to convert to an open procedure.
  • Assessing the Risk of Epstein-Barr Virus–Related Lymphoproliferative Disorders Before Administration of Visilizumab

    • Stephen L. Guthery,
    • Thomas G. Gross
    Published in issue: March 2008
    In the November 2007 issue of Gastroenterology, Plevy et al1 report on the safety profile and biological activity of visilizumab in severe steroid-refractory ulcerative colitis. Although visilizumab seems promising for this challenging clinical problem, we believe that an important subgroup of patients was not identified before receiving visilizumab.