November 2013

Volume 145Issue 5p917-1168, e1-e18

Covering the Cover

  • Covering the Cover

    • Anson W. Lowe,
    • Richard H. Moseley
    Published online: September 23, 2013
    Endoscopy plays an essential role in the management of patients with inflammatory bowel disease and in the evaluation of the efficacy of new treatment modalities. Interobserver variation in the assessment of endoscopic severity of disease in patients with ulcerative colitis and patients with Crohn's disease has led to the development of several activity indices, including the Mayo Clinic Index, the Ulcerative Colitis Disease Activity Index, the Ulcerative Colitis Index of Severity (UCEIS), and the Crohn's Disease Endoscopic Index of Severity (CDEIS), and the Simplified Endoscopic Score for Crohn's Disease (SES-CD), respectively.

Mentoring, Education, and Training Corner


  • Does Consuming the Recommend Daily Level of Fiber Prevent Crohn's Disease?

    • Gilaad G. Kaplan
    Published online: September 23, 2013
    The inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the gut that occur in genetically predisposed individuals exposed to environmental triggers.1 The incidence of IBD continues to increase in the Western world; further, the incidence is rising in developing nations as these countries have become more industrialized.2 Genetic revelations indicate that the pathogenesis of IBD is closely linked to the interplay between the intestinal immune system and microbiota.3 Thus, environmental exposures that modulate the development of IBD are likely associated with a “Westernized” lifestyle that directly influences intestinal immunology and/or alters the composition of the microbiome.
  • Lymphoma: The Bête Noire of the Long-term Use of Thiopurines in Adult and Elderly Patients With Inflammatory Bowel Disease

    • Laurent Beaugerie
    Published online: September 25, 2013
    In this issue of Gastroenterology, Khan et al1 report in a nationwide retrospective study a 4-fold increase in the risk of lymphoma in ulcerative colitis patients exposed to thiopurines. They confirm the extent and the reversibility of the risk reported previously in a prospective nationwide observational cohort,2 and they additionally suggest that the risk gradually increases with duration of therapy.
  • HCV, Ribavirin, and Anemia: A New Dawn

    • Stanislas Pol
    Published online: September 23, 2013
    Since 1995, the treatment of hepatitis C virus (HCV) infection is based on the combination of twice daily weight-based dosing of ribavirin (RBV) and a weekly subcutaneous injection of pegylated interferon alfa (PR), which achieved a sustained virologic response (SVR) in ∼45% of patients with HCV genotype 1, 65% with HCV genotype 4, 70% with HCV genotype 3, and 80% with HCV genotype 2 infection.1,2 Although it has been well understood that RBV improves the SVR rate by significantly reducing the occurrence of relapse or virologic breakthrough, the mechanism of action has remained poorly understood, but likely includes immunoregulatory effects.
  • The Other Genome: Mitochondrial DNA and Protection From Experimental Colitis

    • David L. Boone,
    • Michael A. Teitell
    Published online: September 23, 2013
    Within each eukaryotic cell there are 2 genomes, one encoded by nuclear DNA and the other by mitochondrial DNA (mtDNA). Unlike nuclear DNA, mtDNA can be present in hundreds of copies per cell. mtDNA is replicated and transcribed independently of nuclear DNA to produce (in humans and mice) 22 tRNAs and 2 rRNA genes that function to translate an additional 13 protein coding genes (Table 1). These mtDNA genes encode components for 4 of the 5 respiratory chain complexes of the mitochondrial inner membrane that function in oxidative phosphorylation and thus the production of cellular ATP.
  • Roles for microRNA 23b in Regulating Autophagy and Development of Pancreatic Adenocarcinoma

    • Massimo Donadelli,
    • Marta Palmieri
    Published online: September 25, 2013
    The discovery in 1993 of small endogenous regulatory RNAs in Caenorhabditis elegans led to the identification of a large family of short (∼22 nt), single-stranded ribonucleic acids, termed microRNAs, that function as post-transcriptional regulators of gene expression.1 Since then, microRNAs have been found to regulate many cell processes, and changes in their levels and activities have been associated with many diseases, including cancer. In this issue of Gastroenterology, Wang et al2 report that the microRNA MIR23B regulates autophagy to mediate radioresistance of pancreatic cancer cells.

Gastroenterology in Motion

  • Rectal Endoscopic Submucosal Dissection Made Easy: A Solution to the Retraction Problem

    • Brian P. Saunders,
    • Zacharias P. Tsiamoulos,
    • Huw Thomas,
    • Janindra Warusavitarne
    Published online: September 09, 2013
    With the advent of screening for colorectal cancer and greater awareness of colorectal neoplasia symptoms, increasing numbers of large (>3 cm) sessile or flat rectal polyps are being detected. As polyps become larger, there is an increased risk that they contain submucosally invasive cancer; therefore, radical and complete resection of these high-risk lesions is mandatory. Piecemeal endoscopic mucosal resection is quick, safe, and technically relatively easy; however, it is associated with high recurrence rates, need for close endoscopic follow-up, and provides less than optimal histologic staging.
    Video Abstract

Clinical Challenges and Images in GI

  • Hickam's Dictum in a Patient With Diarrhea

    • Joseph D. Feuerstien,
    • Robert Najarian,
    • Adam S. Cheifetz
    Published online: September 25, 2013
    Question: A 49-year-old woman with a history of 2 cadaveric renal transplants was referred for colonoscopy for evaluation of 4 weeks of bloody diarrhea with associated crampy abdominal pain. Renal transplants occurred in 1998 and 2005 for end-stage renal disease related to glomerulonephritis and subsequent chronic allograft nephropathy. Other past medical history was notable for recurrent urinary tract infections with bilateral ureteral stents placed 6 months ago, immune thrombocytopenic purpura, and hypertension.
  • A Surprising Cause of Abdominal Pain and Bloating

    • Jon Reich,
    • Coleman Smith,
    • Eduardo Ehrenwald
    Published online: September 26, 2013
    Question: A 54-year-old woman presented with diffuse, crampy, episodic abdominal pain present for several years but recently worsening. There was occasional localization to the right upper quadrant and it was exacerbated with eating. She had nausea without emesis, no change in bowel habits, and no improvement with bowel movements. She denied dyspnea and lower extremity edema.
  • An Adult Man With Acute Dysphagia and Systemic Inflammation

    • Margaretha Lind-Anton,
    • Bernhard Rieder,
    • Albrecht Pfeiffer II
    Published online: September 27, 2013
    Question: A 45-year-old man was admitted to the hospital with increasing dysphagia and retrosternal pain of 2 weeks' duration. He denied any weight loss or B-symptoms. The patient had no history of alcohol or nicotine consumption. He was afebrile and the blood pressure was 110/60 mmHg. The physical examination of the oropharynx and thyreoidea was unremarkable. Auscultation revealed decreased breath sounds basal on the patient's left side. Laboratory studies showed leukocytosis (15.8 × 103/ μL) and an increased C-reactive protein level of 67.9 mg/L; troponin and heart enzymes were negative.
  • Dysphagia in Lynch Syndrome

    • Seth Sweetser,
    • Vishal S. Chandan,
    • Todd H. Baron
    Published online: September 27, 2013
    Question: A 35-year-old man with Lynch syndrome presented for evaluation of progressive solid food dysphagia of 2 months’ duration. Lynch syndrome was confirmed by MSH2 mutation testing and family history of young-onset colon cancer. Annual screening colonoscopies since age 25 were normal. Upper endoscopy revealed a 1.5-cm, pedunculated polyp in the proximal esophagus just below the cricopharyngeus (Figure A). Endoscopic ultrasonography of the lesion showed it was confined to the mucosal layer without periesophageal lymphadenopathy.

Electronic Clinical Challenges and Images in GI

  • Unusual Endoscopic Finding

    • Hsu-Heng Yen,
    • Yang-Yuan Chen,
    • Chih-Jung Chen
    Published online: September 26, 2013
    Question: A healthy, 42-year-old, asymptomatic man underwent a screening upper endoscopy. The medical history included a diagnosis of esophageal candidiasis suspected on previous endoscopy 2 years ago (Figure A). At that time, he had no esophageal symptoms and refused biopsy. At the current endoscopy, similar lesions were again found in the esophagus (Figure B, C; Video Clip A). A biopsy was taken.
    Online OnlyVideo Abstract
  • Unifying Diagnosis for Adenomatous Polyps, Café-au-Lait Macules, and a Brain Mass?

    • Carol Durno,
    • Aaron Pollett,
    • Steven Gallinger
    Published online: September 26, 2013
    Question: A 13-year-old girl undergoing surveillance for a familial condition had a brain mass identified on total body magnetic resonance imaging (MRI). She underwent brain MRI, which showed a mass lesion (Figure A). The lesion was resected and histology was consistent with an anaplastic astrocytoma. Her brother had been diagnosed with metastatic duodenal adenocarcinoma at 11 years of age. The family history was significant as parents were first cousins. No other cancers in relatives could be confirmed.
    Online Only
  • Crohn's Disease With Worsening Symptoms

    • Jana G. Hashash,
    • Siobhan Proksell,
    • Miguel D. Regueiro
    Published online: September 26, 2013
    Question: A 27-year-old Caucasian male with Crohn's disease (CD) presented to our gastroenterology suite for a colonoscopy to further evaluate his abdominal pain and diarrhea. The patient was diagnosed with CD at 12 years of age and underwent an extended right hemicolectomy with an ileocolonic anastomosis at age 14 for refractory CD. He had been maintained on mesalamine therapy, 6-mercaptopurine 50 mg/d, and adalimumab (ADA) for many years, but discontinued the ADA a year ago owing to insurance problems.
    Online Only
  • An Intra-Abdominal Mass in a 56-Year-Old Woman

    • Kensuke Adachi,
    • Yukari Takada,
    • Haruka Okada
    Published online: September 26, 2013
    Question: A previously healthy, 56-year-old-woman presented to our hospital with an abdominal mass, approximately 8 × 8 cm in size. This solitary mass had been discovered incidentally by ultrasonography in the course of a routine medical examination. The patient was completely asymptomatic and emphatically denied any weight loss, abdominal pain, change in bowel habits, fever, or signs of bleeding. She also had no abdominal surgery, or history of trauma. Physical examination revealed a firm, large, nontender, and immovable mass in the left upper abdominal quadrant.
    Online Only
  • A Man With Diffuse Vesicular Rash and Epigastric Pain

    • Yu-Guang Chen,
    • Kun-Lun Huang,
    • Chung-Kan Peng
    Published online: September 26, 2013
    Question: A 73-year-old man presented to our hospital with an intermittently spiking fever (maximum temperature, 39.1°C), general malaise, poor appetite, and acute, cramping abdominal pain radiating to the right upper quadrant of his abdomen and back. He had also noticed 2–3 small vesicles on his oral mucosa. Three days after the appearance of the vesicles, this pain gradually worsened. Physical examination revealed abdominal distention and diffuse epigastric tenderness. Disseminated pustular lesions were noted on his trunk and extremities (Figure A, B, arrow).
    Online Only
  • A Rare Cause of Abdominal Pain

    • Bruno Moreira Gonçalves,
    • Ana Célia Caetano,
    • Aníbal Ferreira
    Published online: September 26, 2013
    Question: A 47-year-old woman presented to the emergency room with acute diffuse abdominal pain and emesis. The patient's medical history included hypertension for which she started lisinopril 20 mg 3 days before. On our observation, the vital signs were normal and the abdominal examination revealed periumbilical tenderness, without signs of peritonitis. Laboratory analysis was notable only for a slightly elevated C-reactive protein (6.45 mg/L). Abdominal ultrasonography (Figure A) and computed tomography (Figure B) were taken.
    Online Only

Reviews and Perspectives

    Brief Review

    • Therapeutic Potential of Fecal Microbiota Transplantation

      • Loek P. Smits,
      • Kristien E.C. Bouter,
      • Willem M. de Vos,
      • Thomas J. Borody,
      • Max Nieuwdorp
      Published online: September 09, 2013
      There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal conditions that were not previously considered to be associated with the intestinal microbiota. Although it is not clear if changes in the microbiota cause these conditions, we review the most current and best methods for performing fecal microbiota transplantation and summarize clinical observations that have implicated the intestinal microbiota in various diseases.

    Reviews in Basic and Clinical Gastroenterology and Hepatology

    • The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry

      • Peter J. Kahrilas,
      • Guy Boeckxstaens
      Published online: August 23, 2013
      High-resolution manometry and recently described analysis algorithms, summarized in the Chicago Classification, have increased the recognition of achalasia. It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or with peristalsis. Any of these phenotypes could indicate achalasia; however, without a disease-specific biomarker, no manometric pattern is absolutely specific.

Original Research

Continuing Medical Education (CME) Activities


Selected Summaries

  • Phagocytes Migration in Response to an Emergency Call From the Microbiota

    • Camille Chauvin,
    • Laurent Peyrin-Biroulet,
    • Mathias Chamaillard,
    • Lionel F. Poulin
    Published online: September 20, 2013
    Diehl GE, Longman RS, Zhang JX, et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells. Nature 2013;494:116–120.
  • Fecal Transplantation: Beyond the Aesthetic

    • Kartik Sampath,
    • L. Campbell Levy,
    • Timothy B. Gardner
    Published online: September 20, 2013
    van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent clostridium difficile. N Engl J Med 2013;368:407–415.
  • Reply

    • Josbert J. Keller
    Published online: September 20, 2013
    We thank Kartik Sampath, Campbell Levy, and Timothy Gardner for their review of our study and for the points they raise commenting on our results. The FECAL trial was the first randomized trial providing evidence that donor feces infusion is a powerful therapeutic strategy against Clostridium difficile infection (CDI; N Engl J Med 2013;368:407–415), confirming observations made in previous case series. The study was designed for patients with any recurrence of CDI after ≥1 course of antibiotic therapy (vancomycin or metronidazole) and the estimated success rate of the control arm used for the sample size calculation was 60%, based on reports about treatment outcome of vancomycin in patients with a first recurrence of CDI (Clin Infect Dis 2006;42:758–764).
  • Can Chronic Disease Management Programs Improve Outcomes in Patients With Cirrhosis?

    • Christian A. Mayorga,
    • Amit G. Singal
    Published online: September 23, 2013
    Wigg AJ, McCormick R, Wundke R, et al. Efficacy of a chronic disease management model for patients with chronic liver failure. Clin Gastroenterol Hepatol 2013;11:850–858.
  • Reply

    • Alan J. Wigg
    Published online: September 20, 2013
    We thank the journal for interest in our recent trial and also Drs Mayorga and Singal for their thoughtful comments on our work. A logical starting point for our study was to adopt models that have been successfully used in other chronic diseases to reduce hospitalization, costs, and disease-related mortality. Surprisingly, we were unable to detect any benefits for our primary endpoint of liver-related occupied bed days or any measure of hospitalization.
  • Nucleos(t)ide Analogs-Based Chemoprevention of Liver Cancer in Hepatitis B Patients: Effective, Yet in Search of Optimization

    • Pietro Lampertico,
    • Massimo Colombo
    Published online: September 20, 2013
    Hosaka T, Suzuki F, Kobayashi M, et al. Long-term entecavir (ETV) treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology 2013;58:98–107.

Print and Digital Media Reviews

  • The Tunnel at the End of the Light: My Endoscopic Journey in Six Decades

    • William Brugge
    Published online: September 23, 2013
    Peter Cotton has written a marvelous autobiography (The Tunnel at the End of the Light) of his journeys through the long dark channels of the development of endoscopic retrograde cholangiopancreatography (ERCP). His accounts of introducing ERCP in England at St. Thomas Hospital in 1971 should be an inspiration to all of us who share his dreams of developing new endoscopic procedures. Although there were dark times in the tunnel, his bright personality lit the path to success.
  • Handbook of Gastrointestinal Cancer

    • Lawrence B. Cohen
    Published online: September 23, 2013
    Despite our success in preventing colorectal cancer, gastroenterologists spend considerable time and effort dealing with patients who have gastrointestinal cancers and assisting them in the management of disease-related complications as well as treatment-associated adverse reactions. The Handbook of Gastrointestinal Cancer, edited by Jankowski and Hawk, is intended to provide trainees and practicing gastroenterologists with a handy, concise text designed for point-of-care consultation.