Covering the Cover

  • Covering the Cover

    • Anson W. Lowe,
    • Richard H. Moseley
    Published online: April 29, 2013
    Despite a decreasing burden of peptic ulcer disease and increasing use of proton pump inhibitors, the incidence of nonvariceal upper gastrointestinal bleeding is largely unchanged, suggesting that other undefined risk factors may have an important etiologic role. In this issue of Gastroenterology, Crooks et al, using a well-established database representative of the general English population, conduct a case-control study and develop a model corrected for known risk factors to determine the role of nongastrointestinal comorbidity in nonvariceal upper gastrointestinal bleeding.

Meeting Summary

  • Report From the Multinational Irritable Bowel Syndrome Initiative 2012

    • Mark Pimentel,
    • Nicholas J. Talley,
    • Eamonn M.M. Quigley,
    • Albis Hani,
    • Ala Sharara,
    • Varocha Mahachai
    Published online: May 02, 2013
    In 2012, a group of 29 internationally recognized experts in the pathophysiology, diagnosis, and treatment of irritable bowel syndrome (IBS) convened to audit the current state of IBS research. The meeting was preceded by a comprehensive online survey that focused on research needs for IBS diagnosis (particularly the strengths and shortcomings of current criteria), definitions used in clinical trials for IBS patients and “healthy controls,” potential biomarkers for IBS, and outcome measures in drug trials.
    Online Only

Mentoring, Education, and Training Corner

  • Direct Trainee Observation: Opportunities for Enhanced Physician–Patient Communication and Faculty Development

    • Madhusudan Grover,
    • Douglas A. Drossman,
    • Amy S. Oxentenko
    Published online: April 26, 2013
    The art of effective interviewing and communication skills has dwindled despite the fact that these skills are among the most critical elements of an effective physician–patient relationship (PPR). Enhanced PPR leads to a reduction in physician burnout, malpractice suits, and healthcare costs, meanwhile heightening the capacity to fully understand the patient's illness and concerns, which may be reflected in widely visible patient satisfaction web sites. Increasing patient volumes, perceived attitudes toward particular diagnoses, and insufficient attention by regulatory bodies in charge of education and training has limited professional growth in this critical area.


  • Drug-Induced Liver Injury: Icelandic Lessons

    • Jay H. Hoofnagle,
    • Victor J. Navarro
    Published online: April 26, 2013
    Drug-induced liver injury is among the more challenging forms of liver disease. It occurs without warning, has no specific distinguishing features, and is capable of mimicking almost any form of liver disease. The diagnosis is particularly challenging because there are no specific markers; drug-induced liver injury being a “diagnosis of exclusion” and often only considered after the fact.1,2 The literature on drug-induced liver injury is also challenging because it is immense and spread over hundreds of medical journals in different languages and representing medical disciplines from hepatology to all subspecialties of internal medicine as well as surgery, gynecology, pediatrics, psychiatry, pharmacology, toxicology, genetics, epidemiology, regulatory affairs, and even ethics.
  • Defining Acute-on-Chronic Liver Failure: Will East and West Ever Meet?

    • Jasmohan S. Bajaj
    Published online: April 26, 2013
    The increasing burden of cirrhosis and chronic liver disease worldwide should raise concerns regarding the prevention of morbidity and mortality in these patients.1,2 There is ample evidence that, when patients with cirrhosis develop infections or organ failure, their prognosis is significantly worse than comparable patients without cirrhosis.3 However, research into acute-on-chronic liver failure (ACLF) has been hampered by single-center studies and incongruent definitions. This confusion has led many physicians to believe that ACLF is similar to acute decompensation of cirrhosis.
  • Linking Genetic Variation to Phenotype: eQTL Analysis of Normal Human Ileum

    • Lee A. Denson
    Published online: April 26, 2013
    Gene expression, and thereby the phenotype of the organism, is regulated in a tissue and cell-type specific manner by genetic, epigenetic, and environmental factors.1 Studies over the past decade have begun to define mechanisms by which human gene expression is regulated in a heritable manner, via genetic polymorphisms (SNP), which function as expression quantitative trait loci (eQTL). In fact, the majority of common risk variants for complex diseases identified by genome-wide association studies (GWAS) to date have not been in protein-coding regions, and so may affect risk via regulation of gene expression.
  • Targeting Innate Immunity: A New Step in the Development of Combination Therapy for Chronic Hepatitis B

    • Fabien Zoulim,
    • Souphalone Luangsay,
    • David Durantel
    Published in issue: June 2013
    Current treatments for chronic hepatitis B (HBV) based on nucleos(t)ide analogs (NUC) allow control of viral replication and liver disease in the majority of patients.1,2 However, because NUCs are unable to clear viral covalently closed circular DNA (cccDNA), lifelong therapy is required to maintain the antiviral effect. To define new treatments with finite duration, it is therefore necessary to develop new molecules acting on novel targets to design true combination therapy complementing already existing NUC-based treatment.
  • Hippo Signaling Maintains the Phenotype of Pancreatic Acinar Cells

    • Beatriz Sosa–Pineda
    Published online: April 26, 2013
    Hippo signaling is essential for proper organ growth in both invertebrates and vertebrates. Hippo was first described in Drosophila, and orthologues of all core components of this pathway were later discovered in mammals.1–3 Hippo signaling initiates at the plasma membrane via unknown molecular mechanisms, and is transmitted through a highly conserved core kinase cascade that produces specific transcriptional outputs in different cells. All components of the Hippo pathway ultimately converge into and signal through a common effector, the transcriptional activator Yki (Yap or Taz in mammals).

Gastroenterology in Motion

Clinical Challenges and Images in GI

  • Cramping Pain and Eosinophilic Ascites: What Is the Diagnosis?

    • Paulo Salgueiro,
    • Ricardo Magalhães,
    • Paula Lago
    Published online: April 29, 2013
    Question: A 37-year-old woman presented with a 15-day cramping, diffuse abdominal pain, and increased abdominal size without diarrhea, vomiting, or respiratory or urinary symptoms. Physical examination revealed distended abdomen, slightly painful, with shifting dullness present. She had no fever, rash, or adenopathy. Initial laboratory tests showed leukocytosis (17,000/μL), eosinophilia (2330/μL), C-reactive protein 2.5 times the upper limit of normal, and normal serum albumin (3.58 g/dL). The patient underwent abdominal computed tomography that revealed moderate volume ascites and diffuse thickening of the small bowel (Figure A, B).
  • An Unusual Cause of Elevated Liver Enzymes in a Diabetic Patient

    • Bandar Al-Judaibi,
    • Vincent G. Bain,
    • Banu Sis
    Published online: April 29, 2013
    Question: A 57-year-old man was transferred to a tertiary care center owing to markedly elevated liver function tests. He was symptom free apart from nausea. His past medical history included poorly controlled type 2 diabetes mellitus, chronic renal impairment secondary to diabetes, right below-knee amputation, and left above-knee amputation owing to peripheral vascular disease. He was on insulin, metformin, ramipril, and aspirin. Physical examination was normal except for cushingoid features. Initial laboratory investigations revealed hemoglobin 10.5 g/dL (normal, 13.5–17.5); aspartate aminotransferase, >2600 U/L (normal, <40); alanine aminotransferase, 817 U/L (normal, <50); alkaline phosphatase, 1364 U/L (normal, 30–130); γ-glutamyl transferase, 718 U/L (normal, <70); total bilirubin, 0.88 mg/dL (normal, <1.0); creatinine, 1.69 mg/dL (normal, 0.7–1.4); urea, 66.9 mg/dL (normal, 8–18); albumin, 1.9 g/dL (normal, 3.5–5.0); lactate dehydrogenase >2700 U/L (normal, 100–225); and random glucose, 290.1 mg/dL (normal, 70–110).
  • “Stalk”ing the Etiology of Rectal Bleeding

    • Nicole R. Cullen,
    • Harris G. Yfantis,
    • Erik C. von Rosenvinge
    Published online: April 29, 2013
    Question: A 59-year-old African American man previously treated with brachytherapy for prostate cancer presented to the emergency department with a 3-day history of rectal bleeding. He denied abdominal pain, diarrhea, constipation, or other gastrointestinal symptoms. He had never experienced a similar episode in the past. Physical examination was unremarkable aside from the rectal examination, which showed a small amount of light brown stool with streaks of red blood. Laboratory studies revealed a mild microcytic anemia (hematocrit, 39%; mean corpuscular volume, 79 fL) with normal iron panel.
  • Severe Abdominal Pain 2 Days After Endoscopic Treatment

    • Ping-Hung Ko,
    • Tsung-Hsing Hung,
    • Chih-Wei Tseng
    Published online: April 29, 2013
    Question: A 47-year-old man with a history of decompensated liver cirrhosis was admitted to our hospital owing to the passage of tarry stools for 3 days. The esophagogastroduodenoscopy (EGD) showed a duodenal ulcer with a visible, nonbleeding vessel (Figure A). Endoscopic hemostasis was achieved by clipping the vessel and injection of epinephrine (12 mL, 0.2%; Figure B). Two days later, the patient developed progressive abdominal pain accompanied by nausea, vomiting, and cold sweating. At that time, physical examination revealed tenderness in the epigastric area without muscle rigidity or rebound pain.

Electronic Clinical Challenges and Images in GI

  • Now You See It, Endo You Don't: Case of the Disappearing Knife

    • Sean Fine,
    • James B. Watson,
    • Fadlallah Habr
    Published online: April 29, 2013
    Question: A 32-year-old woman with a psychiatric history of compulsive foreign body ingestions resulting in multiple upper endoscopies and retrievals, presented to the emergency room after swallowing a butter knife approximately 10 hours earlier. Chief symptoms included an inability to rotate her neck, odynophagia, and chest pain. Vital signs revealed an afebrile normotensive patient with a heart rate of 140 bpm. Physical examination of her oropharynx revealed no gross lesions or signs of trauma, crepitus, or palpable mass in the neck.
    Online Only
  • Unusual Cause of Abdominal Pain After Laparoscopic Cholecystectomy

    • Chia-Hsun Tsai,
    • Ming-Chang Tsai,
    • Chun-Che Lin
    Published online: April 29, 2013
    Question: A 66-year-old woman experienced laparoscopic cholecystectomy owing to acute cholecystitis about 7 years ago. She presented with right upper quadrant abdominal pain with fever yesterday and came to our emergency department. Physical examination showed stable vital sign and mild tenderness at the right upper quadrant of abdomen. Laboratory studies yielded a normal leucocyte count with elevated neutrophil percentage and abnormal liver function (alanine aminotransferase, 742 IU/L; alkaline phosphatase, 163 IU/mL; total bilirubin, 1.6 mg/dL).
    Online Only
  • Recurrent Digital Petechiae and Weight Loss in a Young Adult

    • Daniel López Aventín,
    • Lucas Ilzarbe,
    • Josep E. Herrero-González
    Published online: April 29, 2013
    Question: A 38-year-old Caucasian man with no relevant medical history presented to the dermatology department with a 7-month history of recurrent petechiae on the fingers. Anteceding trauma or repetitive pressure were denied. The patient reported occasional local discomfort in the form of stinging pain. The patient also reported a 5-kg weight loss over the past 3 months. He was otherwise in a good health status. Physical examination disclosed several reddish–brown, hemorrhagic maculae on the volar and lateral aspects of the fingertips (Figure A).
    Online Only
  • A Rare Cause of Cobblestoning and Lymphadenopathy

    • Rashid N.S. Lui,
    • Anthony W.H. Chan,
    • Siew C. Ng
    Published online: April 29, 2013
    Question: A 53-year-old Chinese man with good past health presented with a 6-month history of diarrhea, weight loss, and malaise. A colonoscopy showed a long segment of cobblestoning and circumferential narrowing and ulceration in the descending colon, which were suspicious for cancer (Figure A). Left hemicolectomy was performed and the pathology showed no evidence of malignancy. He was well for 3 months, but subsequently developed odynophagia and recurrence of diarrhea. On examination, a left tongue base mass with ulceration and right supraclavicular lymph nodes were noted.
    Online Only
  • A Rare Cause of Cholangiopathy

    • Elizabeth C. Goode,
    • Benedict W. Simpson,
    • Simon M. Rushbrook
    Published online: April 29, 2013
    Question: A previously healthy 20-year-old Caucasian man presented with a 6-month history of weight loss, anorexia, lethargy, and pruritus. Examination revealed conjunctival pallor and hepatomegaly. A full blood count demonstrated iron-deficiency anemia (hemoglobin, 7.8 g/dL; mean corpuscular volume, 63 fL; ferritin, 19 μg/L) and eosinophilia (3.32 × 109/L). Liver function tests showed cholestatic jaundice (bilirubin, 54 μmol/L; alkaline phosphatase, 416 U/L; alanine aminotransferase, 170 μ/L). Noninvasive liver screen, autoantibodies, immunoglobulin (Ig)G4, parasitic cytology, and stool cultures were negative.
    Online Only
  • Abdominal Mass

    • Thomas Pusl,
    • Christian Golling,
    • Thomas Grieser
    Published online: May 01, 2013
    Question: A 60-year-old woman presented to our hospital emergency department with new-onset thoracoabdominal pain. Physical examination was significant only for palpable mass from the right upper quadrant into the pelvic region with minimal pain on deep palpation. A laboratory evaluation was unremarkable except for a slight increase in C-reactive protein (4.9 mg/dL; normal, <0.5) and mild hyperbilirubinemia (total bilirubin, 2.4 mg/dL; normal, <1.2; direct bilirubin, 0.5 mg/dL; indirect bilirubin, 1.9 mg/dL).
    Online Only

Reviews and Perspectives

    Reviews in Basic and Clinical Gastroenterology and Hepatology

    • The Genetics of Complex Cholestatic Disorders

      • Gideon M. Hirschfield,
      • Roger W. Chapman,
      • Tom H. Karlsen,
      • Frank Lammert,
      • Konstantinos N. Lazaridis,
      • Andrew L. Mason
      Published online: April 12, 2013
      Cholestatic liver diseases are caused by a range of hepatobiliary insults and involve complex interactions among environmental and genetic factors. Little is known about the pathogenic mechanisms of specific cholestatic diseases, which has limited our ability to manage patients with these disorders. However, recent genome-wide studies have provided insight into the pathogenesis of gallstones, primary biliary cirrhosis, and primary sclerosing cholangitis. A lithogenic variant in the gene that encodes the hepatobiliary transporter ABCG8 has been identified as a risk factor for gallstone disease; this variant has been associated with altered cholesterol excretion and metabolism.

Original Research

Continuing Medical Education (CME) Activities


  • Presentation of the Julius M. Friedenwald Medal to Chung Owyang, MD

    • Tadataka Yamada
    Published online: April 29, 2013
    Chung Owyang is the recipient of the 2013 Friedenwald Medal, the highest honor bestowed by the American Gastroenterological Association (AGA). For all of his contributions to the field of gastroenterology, he is richly deserving of this award. Chung has been that unique “triple combination” of an academic physician who is equally outstanding as a clinician, scientist, and teacher. His scientific work has always focused on the tight interface between patients and the scientific basis of their illnesses, and the special perspective he has on the pathophysiology of disease has made him both an outstanding clinician and a gifted teacher.

Selected Summaries

  • A Tailored vs Empiric Diet—Which is Best for Eosinophilic Esophagitis?

    • Matthew Greenhawt,
    • Joel H. Rubenstein
    Published online: April 29, 2013
    Spergel JM, Brown-Whitehorn TF, Cianferoni A, et al. Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet. J Allerg Clin Immunol 2012;130:461–467.
  • Proinflammatory Wheat Attacks on the Intestine: Alpha-Amylase Trypsin Inhibitors as New Players

    • Herbert Tilg,
    • Robert Koch,
    • Alexander R. Moschen
    Published online: April 29, 2013
    Junker Y, Zeissig S, Kim SJ, et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of Toll-like receptor 4. J Exp Med 2012;209:2395–2408.
  • Reply

    • Detlef Schuppan,
    • Kristin Gisbert–Schuppan
    Published online: April 29, 2013
    We thank Tilg et al for their thoughtful commentary on our paper describing wheat alpha-amylase/trypsin inhibitors (ATIs) as activators of intestinal innate immunity. We believe that the identification of ATIs as nutritional activators of Toll-like receptor (TLR)4 prominently on macrophages and dendritic cells may have far reaching consequences. Although low-level intestinal TLR4 stimulation seems to be necessary for normal gut integrity (Am J Physiol Gastrointest Liver Physiol 2005;288:G1055–G1065), its overstimulation contributes to intestinal and extraintestinal pathology (Biochem Soc Trans 2007;35:1473–1478).
  • Serrated Polyps Misclassified: The Value of Looking Back and the Impact of Looking Forward

    • Joseph C. Anderson,
    • Douglas J. Robertson
    Published online: April 29, 2013
    Singh H, Bay D, Ip S, et al. Pathological reassessment of hyperplastic colon polyps in a city-wide pathology practice: implications for polyp surveillance recommendations. Gastrointest Endosc 2012;76:1003–1008.
  • Reply

    • Harminder Singh,
    • Charles N. Bernstein,
    • Robert Wightman
    Published online: April 29, 2013
    We enjoyed reading the commentary by Drs Anderson and Robertson on our recent paper in Gastrointestinal Endoscopy. Our interpretation of the current guidelines and the implications of our findings to supplement the current guidelines is slightly different than theirs. For example, Table 1 of the guidelines from the US Multi-society Task Force (MSTF; which are more recent and will be likely the ones most often used in routine clinical practice) only makes recommendations on rectal or sigmoid hyperplastic polyps (HPs) <10 mm in size and does not make recommendations for larger HPs or for HPs reported from the more proximal colon; recommendations for other serrated polyps are limited to that for sessile serrated polyps and traditional serrated adenomas.

Print and Digital Media Reviews

    • Don C. Rockey
    Published online: April 29, 2013
    Schiff's Diseases of the Liver has now reached its 11th edition. The current version, edited by Eugene Schiff, Willis Maddrey, and Michael Sorrell—all fathers of modern hepatology—provides the reader with a comprehensive review of all aspects of hepatology. The book aims to provide a comprehensive review of hepatology, focused on clinical hepatology. As such, its target audience is anyone interested in the field, from student to seasoned expert.
    • Ezra Burstein
    Published online: April 29, 2013
    Injury of the gastrointestinal mucosa, particularly in the upper digestive tract, represents an important clinical problem in gastroenterology. Ranging from peptic ulcer disease to other forms of mucosal injury, this pathophysiologic process has grabbed the imagination and attention of clinicians and scientists alike. Stemming from the seminal observations in 1979 by Andre Robert that prostaglandins can protect the gastric mucosa from a range of injurious agents, the concept of gastric cytoprotection was born.
    • Kim E. Barrett
    Published online: April 29, 2013
    For >30 years, the 2-volume set entitled Physiology of the Gastrointestinal Tract has sought to collect the most current and comprehensive knowledge of the field. Over that time, that field has changed remarkably, from information regarding the cell and molecular biology of the gastrointestinal tract to the recognition that the gut microbiome has profound effects, and should be considered an integral part of the organ system. In the current edition, the content continues to keep pace with major developments, with 5 sections focused on Basic Cell Physiology, Genetics and Growth of the GI Tract; Neurogastroenterology; Host Defense Mechanisms; Physiology of Secretion; and Digestion and Absorption.