July 2013

Volume 145Issue 1p1-262, e1-e17
  • Seventy Years of Gastroenterology (1943–2013)

    • Raj K. Goyal
    Published in issue: July 2013
    During a cab ride from a meeting of the American Gastroenterological Association (AGA) to Reagan National Airport in Washington, DC, Gastroenterology Editor-in-Chief Omary asked me to consider writing a historical overview of the Journal. Although I exuberantly supported the idea, I felt a bit overwhelmed at the beginning. However, now that it is complete, I am glad I did it.
  • Gastroenterology's Editors-in-Chief: Historical and Personal Perspectives of Their Editorships

    • John S. Fordtran,
    • Raj K. Goyal,
    • Mark Feldman,
    • ...
    • David A. Brenner,
    • Anil K. Rustgi,
    • M. Bishr Omary
    Published in issue: July 2013
    Fourteen editors-in-chiefs have steered Gastroenterology to success since its inception in 1943. Five (Alvarez, Ivy, Aaron, Grossman, and Donaldson) are no longer with us. Their personalities and editorships, along with those of Marvin Sleisenger, are presented by their admirers. Fordtran, Ockner, Goyal, LaRusso, Podolsky, Brenner, Rustgi, and Omary describe their own backgrounds, experiences, and personal reflections on serving as editor-in-chief of Gastroenterology.

Covering the Cover

  • Covering the Cover

    • Anson W. Lowe,
    • Richard H. Moseley
    Published online: May 31, 2013
    In recent years, esophageal adenocarcinoma has garnered increasing interest because of its rising incidence. Barrett's esophagus represents a precursor lesion characterized by intestinal metaplasia that may progress to dysplasia and finally cancer. Patients who exhibit high-grade dysplasia carry a significant risk for progressing to esophageal adenocarcinoma, which led to acceptance of esophagectomy as a viable therapeutic option despite its significant complication rate.

Mentoring, Education, and Training Corner

  • Time Management in the Busy Professional Environment: Take That First Step

    • Francisco H. Andrade
    Published online: May 24, 2013
    I am sure it was the catchy title, but do you really have time to read this? Is there something else, maybe more important, you should be doing? Welcome to the club: we rush from meeting to meeting, and are stressed by fast approaching (past?) deadlines, slaves to Outlook, smartphones, and clinical schedules. Our time is not “ours”: It is at the whim of others, meted in 15-minute intervals. Yet, we never stop and question why it is that way. That universal maxim “time is money” holds sway; we must justify every moment of our professional existence, sometimes at the expense of other areas of our lives.


  • Can You Stop Surveillance After Radiofrequency Ablation of Barrett's Esophagus? A Glass Half Full

    • Douglas A. Corley
    Published online: June 03, 2013
    The concept of ablation for Barrett's esophagus creates considerable enthusiasm: It offers the potential for changing the management paradigm of this precancerous condition from surveillance for early cancer to prevention.1 Patients with Barrett's esophagus and high-grade dysplasia have a substantially elevated risk of developing esophageal adenocarcinoma; this is associated with increased cancer-related anxiety (a greater than 10-fold overestimate of cancer risk), decreased quality of life, and enhanced use of medical resources (21% higher overall costs than patients with gastroesophageal reflux disease and 62.4% higher overall costs than a general population).
  • Novel Oral Anticoagulants: Is the Convenience Worth the Risk?

    • Steven J. Heitman,
    • Elizabeth MacKay,
    • Robert J. Hilsden,
    • Alaa Rostom
    Published online: June 03, 2013
    Vitamin K antagonists, heparins, and antiplatelet agents have been the cornerstones of antithrombotic therapy for decades. These agents are effective and are recommended for the prevention and treatment of thrombotic events across a spectrum of diverse clinical settings.1 However, the need for regular drug monitoring and dose adjustments resulting from dietary changes and drug interactions for those taking warfarin, and the need for subcutaneous administration of low-molecular-weight heparins, remain significant limitations.
  • What You See is Not Always What You Get: Raising the Bar on Clinical Trial Methodology in Ulcerative Colitis

    • David T. Rubin
    Published online: May 31, 2013
    Performing high-quality trials in ulcerative colitis (UC) is an enormously expensive proposition. In addition to the many years and millions of dollars invested in product development and preclinical and early phase clinical trials, the successful completion of phase III trials has a large number of challenges. Ideally, such pivotal trials are designed to accurately demonstrate the true clinical efficacy and safety of the novel product and to be free from methodological flaw or investigator error.
  • Looking Forward to Understanding and Reducing Colorectal Cancer Risk in Inflammatory Bowel Disease

    • Fernando S. Velayos,
    • Thomas A. Ullman
    Published online: June 03, 2013
    The link between colorectal cancer (CRC) and inflammatory bowel disease (IBD) was described nearly a century ago. Since then, a variety of epidemiologic and experimental approaches have been used by researchers to study this complex topic area, to better understand this link, and, most important, to mitigate this risk. This collective experience and scientific knowledge has been a work in progress. Hypotheses are routinely generated, tested, confirmed, modified, or dismissed based on observations and experiments.
  • Molecular Diagnostic Algorithms in Hepatocellular Carcinoma: Dead-End Street or Light at the End of the Tunnel?

    • Peter Schirmacher,
    • Diego F. Calvisi
    Published online: June 03, 2013
    Hepatocellular carcinoma (HCC) is one of the most frequent and deadliest cancers worldwide.1,2 Despite its enormous clinical relevance, therapeutic options have remained limited.3–5 No curative, systemic treatment exists to date and only limited lifespan extension can be reached by established palliative therapy, despite increased treatment options over the last years (eg, local ablative technologies, transarterial chemoembolization [TACE], sorafenib, endoradiotherapy).3–10 Curative approaches mainly reside on surgery, that is, partial liver resection or transplantation (LTX).
  • Primary Liver Carcinomas Can Originate From Different Cell Types: A New Level of Complexity in Hepatocarcinogenesis

    • Jessica Zucman–Rossi,
    • Jean–Charles Nault,
    • Lars Zender
    Published online: May 31, 2013
    Primary liver carcinomas (PLC) in adults comprise hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), 2 morphologically, genomically, and clinically very heterogeneous tumors with dismal clinical outcomes.1 For a long time, it has been the prevailing view that hepatocytes represent the target cell for oncogenic transformation in HCC and cholangiocytes in CCA. However, work over the past decade has suggested that, in addition to hepatocytes and cholangiocytes, PLC may be derived from adult liver stem/progenitor cells.

Gastroenterology in Motion

  • In Vivo Molecular Imaging of Barrett's Esophagus With Confocal Laser Endomicroscopy

    • Matthew B. Sturm,
    • Cyrus Piraka,
    • B. Joseph Elmunzer,
    • ...
    • Henry D. Appelman,
    • D. Kim Turgeon,
    • Thomas D. Wang
    Published online: May 16, 2013
    Esophageal adenocarcinoma (EAC) arises from Barrett’s esophagus, a columnar metaplasia of the epithelium caused by chronic acid reflux.1 This disease is growing faster than any other type of cancer in western countries,2 and despite extensive efforts for prevention, the incidence remains high and the 5-year survival rate is poor. Early detection may allow for more effective interventions and is critical to improving prognosis. Current methods of surveillance with white light endoscopy are limited in effectiveness because pre-malignant lesions (dysplasia) are flat in appearance and difficult to visualize.
    Video Abstract

Clinical Challenges and Images in GI

  • An Unusual but Important Cause of Biliary Obstruction

    • Wei-Fang Chang,
    • Guo-Shu Huang,
    • Wei-Chou Chang
    Published online: June 03, 2013
    Question: A 75-year-old man presented to our hospital with tea-colored urine and episodic upper abdominal pain for 1 month. He denied fever, chills, or weight loss. The patient underwent a cholecystectomy 30 years ago and did not have any history of chronic cholangitis or pancreatitis. Physical examination revealed icteric sclera and jaundice. Laboratory testing revealed elevated total/direct bilirubin level (19.3/14.8 mg/dL) and alkaline phosphatase level (718 U/L). Tumor markers showed high CA 19-9 level (300 U/mL), but normal range of carcinoembryonic antigen and alpha-fetoprotein level.
  • A Rare Cause of Caustic Gastric Injury in a Young Man

    • Lara Younan,
    • Mohamad Eloubeidi,
    • Kassem Barada
    Published online: June 03, 2013
    Question: A 42-year-old previously healthy man presented to the emergency ward with severe epigastric pain and multiple episodes of coffee ground emesis. He reported that 12 hours earlier, he accidentally ingested 20 g of a household antiseptic. He dissolved 20 g of a dark purple powder in 300 mL of water and then drank it. Upon presentation, his vital signs were stable. There was no evidence of respiratory distress or stridor. Oral examination revealed purple discoloration of the tongue with significant uvular swelling.
  • Second Opinion

    • Khalid Rasheed,
    • Leona Council,
    • Frederick H. Weber Jr.
    Published online: June 03, 2013
    Question: A 47-year-old, asymptomatic woman was self-referred for evaluation of diffuse colorectal polyposis. Recent colonoscopy revealed >100, diffuse, 3- to 7-mm polyps throughout the colon and rectum reported as mixed hyperplastic polyps and tubular adenomas without high-grade dysplasia; colectomy was recommended by her initial gastroenterologist. Her past medical history included nephrectomy for hypernephroma at age 38, hysterectomy with bilateral oophorectomy for uterine fibroids and ovarian cysts, partial thyroidectomy for multinodular goiter, and removal of oral papillomas and soft cutaneous nodules.
  • A Rare Cause of Gastrointestinal Bleeding

    • Yen-Po Wang,
    • Ying-Ru Kuo,
    • Ching-Liang Lu
    Published online: June 03, 2013
    Question: A 60-year-old woman presented to our emergency room with epigastric fullness and passage of tarry stool for 1 week. She also had progressive shortness of breath, dizziness, and generalized weakness. On physical examination, slight tachycardia (heart rate, 104 bpm) with anemic conjunctiva was noted. Blood tests showed low hemoglobin (6.9 g/dL). Esophagogastroduodenoscopy revealed a polypoid tumor with superficial ulcerations and hematin coatings, suggesting recent bleeding, near superior duodenal angle of duodenum (Figure A).

Electronic Clinical Challenges and Images in GI

  • A 44-Year-Old Patient With Fever, Night Sweats, and Arthralgia

    • Thomas Karlas,
    • Joachim Mössner,
    • Volker Keim
    Published online: June 03, 2013
    Question: A 44-year old man presented with fatigue, intermittent fever, and night sweats. His symptoms started 10 days earlier. Furthermore, he reported painful knee joints after physical exercise for the last week. He experienced similar, self-limiting episodes of arthralgia 1 and 2 years ago. The patient stopped smoking 10 years earlier (20 pack-years). Further personal medical and travel history were uneventful.
    Online Only
  • Cut Loose and Cast Adrift

    • Tim Ambrose,
    • Brendan Barry,
    • Antony J. Ellis
    Published online: June 03, 2013
    Question: A 59-year-old man with a body mass index of 47 kg/m2 was referred to the gastroenterology department with a 6-week history of persistent, nonbloody diarrhea. His past medical history included nonalcoholic fatty liver disease, appendectomy, and an adjustable gastric band fitted laparoscopically 6 years previously. He consumed 25–40 units of alcohol per week. Examination revealed morbid obesity.
    Online Only
  • A Heart of Stone

    • Nirav Thosani,
    • Mamoun Younes,
    • Jen-Jung Pan
    Published online: June 03, 2013
    Question: A 33-year-old woman with past medical history of hypertension, coronary artery disease with congestive heart failure and end-stage renal disease (ESRD) was admitted with worsening bilateral lower extremity pain. She had a long-standing history of recurrent kidney stones since age 12 and ultimately developed ESRD at the age of 27. Over the last 6 months, she developed worsening peripheral vascular disease with diffuse ulcerations with eschar formation over bilateral feet and legs (Figure A) and presented to our institution.
    Online Only
  • A Rare Cause of Colitis

    • Jordy P.W. Burger,
    • Marcel J.M. Groenen,
    • B.W. Marcel Spanier
    Published online: June 03, 2013
    Question: An 82-year-old woman presented to the emergency room with progressive rectal bleeding and diarrhea for over 1 week. She did not have abdominal complaints or a fever. Her previous medical history included radical transurethral resection of a pTaG2a bladder cancer in 2001. She used no anticoagulants or nonsteroidal anti-inflammatory drugs. Hemodynamic parameters were stable and body temperature was normal. No lymphadenopathy or abdominal masses were found. Rectal examination revealed fresh blood without palpable mass.
    Online OnlyVideo Abstract
  • Beware of the Patient With a Glass Eye and Large Liver

    • Magnus Halland,
    • Steven Bollipo,
    • Stephen Philcox
    Published in issue: July 2013
    Question: An 88-year-old man presented with a 1-week history of left upper quadrant abdominal pain and jaundice on a background of a 2-month history of back pain and malaise. His background medical history was notable for hypertension, hypercholesterolemia, and melanoma. On examination, his pulse rate was 76 bpm and blood pressure, 112/64 mmHg. He was febrile (101.8°F; 38.8°C). Peripherally, there was no palmar erythema or clubbing, but spider angiomas were noted (Figure A). He was not encephalopathic, but had diffuse abdominal tenderness, hepatomegaly with a firm liver edge, and ascites.
    Online Only
  • Penile Nodules: Whose Problem?

    • Kensuke Adachi,
    • Yuki Tateno,
    • Kazuaki Enatsu
    Published online: June 03, 2013
    Question: A 65-year-old man visited our department during postoperative radiotherapy for an anorectal carcinoma (ARC) with painful penile induration. There were no signs of fever, dysuria, or inguinal lymphadenopathy. On examination, multiple discrete nodules up to 10 mm in diameter were palpable under the prepuce. Three months before the present consultation, the patient underwent abdominoperineal resection for locally advanced ARC. Preoperative radiographic examination could not detect these lesions.
    Online Only

Reviews and Perspectives

    Reviews in Basic and Clinical Gastroenterology and Hepatology

    • The Gastrointestinal Tumor Microenvironment

      • Michael Quante,
      • Julia Varga,
      • Timothy C. Wang,
      • Florian R. Greten
      Published online: April 12, 2013
      Over the past decade, the microenvironment of gastrointestinal tumors has gained increasing attention because it is required for tumor initiation, progression, and metastasis. The tumor microenvironment has many components and has been recognized as one of the major hallmarks of epithelial cancers. Although therapeutic strategies for gastrointestinal cancer have previously focused on the epithelial cell compartment, there is increasing interest in reagents that alter the microenvironment, based on reported interactions among gastrointestinal epithelial, stromal, and immune cells during gastrointestinal carcinogenesis.

Original Research

Continuing Medical Education (CME) Activities

Selected Summaries

Print and Digital Media Reviews

  • Gastrointestinal and Liver Disease Nutrition Desk Reference

    • Edward Saltzman
    Published online: June 03, 2013
    This book is a multi-author collection of 32 chapters representing an array of nutrition topics in gastroenterology and hepatology. The book is not an encyclopedic desk reference that practitioners are likely to employ when needing very detailed information about a narrow topic. Rather, it is a textbook that several types of clinicians, including physicians, advanced practice nurses, physician assistants, and nutritionists, will find useful. The book covers the role of nutrition in preventing, promoting, and treating gastrointestinal diseases as well as how these diseases influence nutrient needs.
  • Histopathology of Chronic Constipation

    • Giuseppe Martucciello
    Published online: June 03, 2013
    Intestinal peristalsis is the result of a complex process involving all components of bowel wall: the enteric nervous system (ENS), the tendinous collagenous tissue of muscularis propria, and muscularis layer itself. A malfunction of any of these parts leads to constipation and abnormal peristalsis. One of the best textbooks on this subject is this new monograph, which has a hard cover and includes 54 pages, as well as 105 figures (93 in color), 6 tables, and schematic drawings of high quality.
  • Self-Expandable Stents in the Gastrointestinal Tract

    • Douglas G. Adler
    Published online: June 03, 2013
    Self-Expandable Stents in the Gastrointestinal Tract, edited by Richard Kozarek, Todd Baron, and Ho-Young Song, reviews for the reader the current state of the art of endoscopic stenting in all regions of the gastrointestinal tract. The book includes separate chapters on stenting in the esophagus, gastroduodenum, colon, and biliary tree, and is illustrated by many black-and-white and color images of high quality. The index is detailed and seems to be complete. The title is somewhat of a misnomer; that rigid prostheses of both the esophagus and bile ducts are given separate chapters and discussed thoroughly, so the book does in fact cover more than self-expandable stents.


  • Low Hepatocyte Repopulation From Stem Cells: A Matter of Hepatobiliary Linkage Not Massive Production

    • Neil D. Theise,
    • Laurent Dollé,
    • Reiichiro Kuwahara
    Published online: June 03, 2013
    The contribution of resident hepatobiliary stem/progenitor cells (HSPCs) to the restoration of hepatocyte mass remains a contentious subject. On one hand, abundant hepatocyte repopulation from HSPCs has been confirmed in late stage human disease (chronic viral hepatitis1–3 and other toxic and metabolic diseases2). On the other hand, such robust restoration remains uncertain for severe acute human injuries. Animal models (which are primarily single hit or repetitive acute injuries) have mostly failed to demonstrate robust repopulation.
  • Utility of Osteopontin in Lineage Tracing Experiments

    • Jason Coombes,
    • Wing–Kin Syn
    Published online: June 03, 2013
    Espanol–Suner et al recently reported that liver progenitor or biliary cells terminally differentiate into functional hepatocytes in mice with chronic liver injury.1 They generated the osteopontin (OPN)-iCreERT2; Rosa26RYFP mice to genetically trace the fate of liver progenitors (YFP-positive cells). Liver progenitors and their progeny are detected by expression of enhanced YFP. OPN was selected to drive iCreETT2 expression because expression of OPN was considered to be restricted within cholangiocytes/liver progenitor cells.
  • Reply

    • Regina Español–Suñer,
    • Frédéric P. Lemaigre,
    • Isabelle A. Leclercq
    Published online: June 03, 2013
    In the normal, unharmed adult liver, the matricellular protein osteopontin (OPN) is restrictedly expressed in K19+ and SOX9+ cholangiocytes and liver progenitor cells (LPC) and immunoreactive OPN was not detected in any other cell types.1 By contrast, in pathologic states, various cell types in inflammatory foci may highly express OPN.2 In liver injury, besides LPC/biliary cells, inflammatory cells (mainly lymphocytes) and some peribiliary hepatocytes express OPN. However, no co-localization between immunoreactive OPN and α-smooth muscle actin was found in mice exposed to choline-deficient, ethionine-supplemented (CDE) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) regimes, suggesting that OPN expression was not induced or not detectable by immunohistochemistry in activated hepatic stellate cells/myofibroblasts in those models.