February 2018

Volume 154Issue 3p453-766, e1-e24

Gastroenterology's Diamond Anniversary: 1943–2018

  • Viral Hepatitis: Knowledge and Treatments for Hepatitis B and C Virus and Associated Transplantation and Neoplasia

    • Kenneth E. Sherman,
    • Vijay H. Shah
    Published online: November 14, 2017
    The last 20 years have witnessed major advances in our understanding of the epidemiology, natural history, and treatment of viral hepatitis B and C (Figure 1). Key publications in Gastroenterology moved the field of viral hepatitis forward. Indeed, more than 50 articles provided key insights, as evidenced by high levels of citation in the field, and it is difficult to highlight a small subset of truly seminal findings that have had a major effect on the field. With that caveat, we can examine the role played by a few of these articles.

Covering the Cover

  • Covering the Cover

    • Andrew T. Chan,
    • Christopher S. Williams
    Published online: January 11, 2018
    In a randomized, double-blind, placebo-controlled crossover trial among patients with nonceliac gluten hypersensitivity, fructan, but not gluten, was associated with higher irritable bowel syndrome scores.


  • State of the Journal: CMGH’s Progress, Prospects, and Impact Factor

    • Jerrold R. Turner,
    • James R. Goldenring,
    • Maria Rescigno,
    • Rebecca G. Wells
    Published in issue: February 2018
    Cellular and Molecular Gastroenterology and Hepatology (CMGH) was established to create a forum for high-quality, mechanistic studies of the gastrointestinal tract, liver, and pancreas. CMGH has now completed its third full year of publication and has developed a reputation as a rigorous and highly regarded platform for basic and translational research. CMGH has also become known for a prompt, fair, and transparent review process in which authors are treated with respect and have access to editors.
  • Update on the Use of Vonoprazan: A Competitive Acid Blocker

    • David Y. Graham,
    • Maria Pina Dore
    Published online: January 11, 2018
    Vonoprazan (TAK-438), a potassium-competitive acid blocker, inhibits acid secretion by competitively blocking availability of potassium to hydrogen-potassium ATPase. Chemically it is a pyrrole derivative (1-[5-(2- fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate) currently being developed by the Takeda Pharmaceutical Company.1,2 Vonoprazan is acid stable and rapidly absorbed fasting or fed, reaching Cmax by 1.5–2.0 hours. It dissociates slowly from its target (half-life of approximately 7.7 hours).

Mentoring, Education, and Training Corner

  • How to Obtain Training in Nutrition During the Gastroenterology Fellowship

    • Dejan Micic,
    • Edwin K. McDonald,
    • Adam C. Stein,
    • Carol E. Semrad
    Published online: January 11, 2018
    The role of diet and nutrition is becoming increasingly recognized in the cause, prevention, and management of disease. A lack of training in the field of nutrition has been recognized in multiple subspecialty fields,1 and is highlighted by a shortage of physicians trained to manage disease-related malnutrition.2 Given the central role of the gastrointestinal system in the field of nutrition, gastroenterologists have the unique potential to take a leading role in the research, management, and training of nutrition as it relates to disease and health for future generations.


  • Nonceliac Gluten Sensitivity: What Is the Culprit?

    • Kristin Verbeke
    Published online: January 11, 2018
    In 1978, the term nonceliac gluten sensitivity (NCGS) was coined in a case report describing the resolution of persistent gastrointestinal symptoms in a patient (in which celiac disease had been excluded) with the adoption of a gluten-free diet.1 Currently, NCGS has been defined as a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that resolve once the gluten-containing foodstuff is eliminated from the diet and when celiac disease and wheat allergy have been ruled out.
  • Colonoscopy Risks: What Is Known and What Are the Next Steps?

    • Cynthia W. Ko
    Published online: January 11, 2018
    Colonoscopy is an essential, commonly used tool in gastroenterology, with a primary role in colorectal cancer prevention as well as the diagnosis and management of lower gastrointestinal symptoms. However, colonoscopy is associated with potentially serious complications, and the risk of adverse events has been a topic of extensive study. In this issue of Gastroenterology, Wang et al1 provide important new data regarding the risks of both diagnostic and screening/surveillance colonoscopy.
  • Intraductal Papillary Mucinous Neoplasm as the Focus for Early Detection of Pancreatic Cancer

    • Masao Tanaka
    Published online: January 11, 2018
    The only chance of cure for pancreatic cancer depends on its early detection and appropriate resection. The early detection of the disease relies on the detection and surveillance of high-risk individuals. Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is one of pancreatic cancer precursors that is easy to detect and follow; thus, adequate surveillance of IPMN patients may allow the early detection of resectable pancreatic cancers.1
  • Development of the Enteric Nervous System: A Genetic Guide to the Perplexed

    • Michael D. Gershon
    Published online: January 11, 2018
    The critical and obvious role that the bowel plays in the life of an organism is to be the site where digestion and absorption of ingested food occurs. These functions, however, are not simply accomplished, but require enteric motility and management by the nervous system. In addition to its well-known roles in controlling gastrointestinal motility and secretion, the nervous system regulates mucosal epithelial growth,1,2 as well as gastrointestinal manifestations of immunity and inflammation.3,4 Although the gut has long been known to be able to function independently of input from the central nervous system (CNS),5 it cannot function independently of input from its intrinsic enteric nervous system (ENS); a lethal pseudo-obstruction occurs when even a small segment of bowel is aganglionic.
  • NVR 3-778 Plus Pegylated Interferon-α Treatment for Chronic Hepatitis B Viral Infections: Could 1 + 1 = 3?

    • John E. Tavis,
    • Elena Lomonosova
    Published online: January 11, 2018
    Treatment for chronic hepatitis B virus (HBV) infection primarily uses monotherapy with nucleos(t)ide analogues or (pegylated)interferon-α (peg-IFN).1 These therapies can effectively suppress viral replication and significantly improve liver function. However, loss of hepatitis B surface antigen (HBsAg) is rare with either type of therapy, and treatment does not completely stop disease progression in all patients.2 Furthermore, interferon can cause substantial side effects, and nucleos(t)ide analogue therapy often needs to be continued indefinitely, leading in some cases to resistance to the nucleos(t)ide analogues and potential long-term side effects.
  • Pancreatitis: A Tale of Two Proteases

    • Aniket Nikam,
    • Rajinder Dawra,
    • Ashok Saluja,
    • Vikas Dudeja
    Published online: January 11, 2018
    With no targeted treatment available, therapy of pancreatitis is focused on management of symptoms and providing supportive care.1 Thus, a long-standing goal in the field has been to decipher the pathogenesis of pancreatitis to design effective treatment options.2 One of the most popular theories, and certainly one that has captured the imagination of pancreatologists for the longest time, is to view pancreatitis as an autodigestive disease, that is, a process in which the pancreas is digested by its own enzymes.

Gastroenterology in Motion

  • Noninvasive Diagnosis of Pancreatic Cancer Through Detection of Volatile Organic Compounds in Urine

    • Ramesh P. Arasaradnam,
    • Alfian Wicaksono,
    • Harrison O’Brien,
    • Hemant M. Kocher,
    • James A. Covington,
    • Tatjana Crnogorac-Jurcevic
    Published online: November 09, 2017
    With its incidence approaching mortality, and with >300,000 new cases diagnosed worldwide in 2013, pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related death and predicted to become the second by 2030.1 More than 80% of patients with PDAC are diagnosed late,2 with locally invasive and/or metastatic disease, resulting in negligible 5-year survival. Thus, the quest for a simple, inexpensive, and noninvasive test to detect PDAC early, while it is still amenable to surgical resection, continues.
    Online ExtraVideo AbstractCME QuizAdditional Online Content Available

Clinical Challenges and Images in GI

  • An Unexpected Cause of Recurrent Melena

    • Liansong Ye,
    • Shan Jiang,
    • Bing Hu
    Published online: January 16, 2018
    Question: A 62-year-old man was referred to our hospital with 2 years of recurrent symptomatic melena requiring multiple blood transfusions and iron therapy. His past medical history was not significant. His physical examination was unremarkable and laboratory tests were significant for mild anemia (hemoglobin, 11 g/dL; mean corpuscular volume, 96.9 fL). Initial bidirectional endoscopy revealed small amount of hematin stain in the hepatic flexure and mild ileum erythema was found on capsule endoscopy (Figure A).
  • Unexpected Findings in a Patient With Cancer of Unknown Primary Syndrome

    • Christoph Lübbert,
    • Babett Holler
    Published online: January 17, 2018
    Question: A 60-year-old Caucasian man was referred to our department for restaging of cancer of unknown primary syndrome with peritoneal carcinosis (confirmed by diagnostic laparoscopy), which had been diagnosed 8 months before. The patient had already undergone 6 cycles of combination chemotherapy with fluorouracil, leucovorin, oxaliplatin, and panitumumab (FOLFOX/Vectibix) for histologic and immunohistochemical diagnosis of adenocarcinoma (colorectal type, KRAS wild type). Physical examination was unremarkable, blood tests showed a moderate anemia (hemoglobin, 11.9 g/dL), and normal differential blood count; other laboratory tests were uninformative.
    Additional Online Content Available
  • Hepatic Mass in a Patient With Bladder Cancer History

    • Natally Horvat,
    • Monica Ragucci,
    • Lorenzo Mannelli
    Published online: January 16, 2018
    Question: An 82-year-old asymptomatic man presented with an incidental finding of liver lesion on a computed tomography (CT) angiogram performed for infrarenal abdominal aortic aneurysm repair surveillance. He had a history of bladder cancer 7 years prior, with no evidence of disease since the end of the treatment. He did not have history of liver disease or immunosuppression. At presentation, his laboratory examinations were normal. He underwent abdominal magnetic resonance imaging (MRI) that showed a 3.5 × 3.0-cm liver mass in segment II/IVA; the mass was T2-weighted images mildly hyperintense (Figure A, arrow) and T1-weighted image hypointense (Figure B, arrow) to the background liver, and demonstrated hyperenhancement in the arterial phase (Figure C, arrow), and heterogeneous enhancement and capsule on the delayed phase (Figure D, arrow).
  • Persistent Fever and Abdominal Pain in a Young Woman With Budd-Chiari Syndrome

    • Elisa Liverani,
    • Antonio Colecchia,
    • Giuseppe Mazzella
    Published online: January 17, 2018
    Question: A 23-year-old woman with Budd-Chiari syndrome in treatment with warfarin was admitted to our unit because of the persistence of fever, severe abdominal pain, diarrhea, and marked weight loss. Her medical history included recurrent oral and genital aphthous ulcers, arthritis, and erythema nodosum. Two months before admission, she underwent urgent left hemicolectomy for a massive intestinal hemorrhage. Treatment with corticosteroids was started after diagnosing probable Behçet’s disease (BD).

Electronic Clinical Challenges and Images in GI

  • Enteritis and Rapid-Onset Renal Dysfunction in a Previously Healthy Adult

    • Divya B. Bhatt,
    • Anil Seetharam
    Published online: January 29, 2018
    Question: A 49-year-old Caucasian man with a past medical history of hyperlipidemia presented with colicky, generalized abdominal pain of 3 weeks’ duration. He had traveled to Mexico 3 months prior; however, he denied sick contacts or antibiotic usage, ingested bottled water exclusively, and adhered to a vegan diet. Three days before presentation, he developed a bilateral lower extremity purpuric rash (Figure A) and intermittent melenic stool. Upon presentation, he was noted to have a leukocytosis of 30,300/mm3, creatinine of 0.8 mg/dL, hemoglobin of 15.7 g/dL, platelets of 287,000/mm3, and an International Normalized Ratio of 1.2.
    Online Only
  • A Rare Cause of Chronic Anemia and Recurrent Bowel Obstruction

    • Shan-Ming Chen,
    • Teng-Fu Tsao,
    • Hsiang-Lin Lee
    Published online: January 19, 2018
    Question: A 12-year-old boy presented with a history of iron deficiency anemia for which he had taken oral iron supplementation for 2 years. He also complained of intermittent right hip pain in recent years. He had no weight loss, no prolonged fever or abdominal pain, and had regular bowel movements, except for dark-colored stool at times. He was referred to our pediatric clinic because his stool was guaiac positive, where his hemoglobin level was 6.6 g/dL and platelet count, blood clotting time, C-reactive protein level, and urinalysis results were normal.
    Online Only
  • A Flat Tire in the Colon

    • Vincent Zimmer,
    • Philipp A. Schnabel,
    • Frank Lammert
    Published online: January 17, 2018
    Question: A 45-year-old man with no significant medical history except for vague intermittent abdominal pain was referred for an endoscopic second opinion after previous colonoscopy had been pertinent for multiple segmental submucosal lesions. Previous mucosal histopathology was nonspecific and, computed tomography was considered to exhibit uncomplicated diverticulosis.
    Online Only
  • An Unusual Cause of Abdominal Pain in a Young, Hypertensive Female

    • Kevin L. Huang,
    • Yih C. Lin,
    • Kellee L. Oller
    Published online: January 17, 2018
    Question: A 21-year-old woman of Indian descent presented with subacute left upper quadrant abdominal pain. The pain was sharp, severe, and elicited by food. She denied diarrhea, constipation, and weight loss. Her past medical history was significant for hypertension diagnosed as a teenager and ischemic stroke, attributed to Moya-Moya disease, and treated with stenting and bypass of the left middle cerebral and internal carotid arteries. Her medications included amlodipine, aspirin, and topiramate.
    Online Only
  • Unusual Cause of Dysphagia

    • Vincent Verdier,
    • Minh Dung Ngo,
    • Richard Petit
    Published online: July 13, 2017
    Question: A 94-year-old man was referred to the gastroenterologist complaining of dysphagia associated with impaired general condition. He underwent antrectomy and segmental colectomy for intestinal obstruction 40 years ago. He denied smoking and alcoholism. He reported having a semisolid diet for many years. Physical examination without any particularity. Upper gastrointestinal endoscopy showed difficulty to pass through an extrinsic compression of the posterior pharyngoesophageal wall (Figure A).
    Online Only
  • An Elderly Woman With Upper Abdominal Pain and a 60-Pound Weight Loss

    • Dalbir S. Sandhu,
    • Andrew M. Bellizzi,
    • Rami El Abiad
    Published online: July 13, 2017
    Question: A 63-year-old African American woman presented with 2 years of nausea, vomiting, upper abdominal pain, and a 60-pound weight loss with no reported diarrhea or gastrointestinal bleeding. Her outside hospital workup included esophagogastroduodenoscopy, colonoscopy with biopsies, and a video capsule endoscopy that showed gastric mucosal edema. Celiac serologies were negative and an empiric gluten-free diet failed to resolve her symptoms. She was admitted with severe malnutrition and started on total parenteral nutrition.
    Online Only

Practical Teaching Case

  • The Role of Anchoring in Working Up Diarrhea: A Practical Teaching Case

    • Claire L. Jansson-Knodell,
    • Sahil Khanna
    Published online: October 13, 2017
    Question: A 48-year-old woman with a family history of Crohn’s disease in her mother, sought gastroenterology consultation for a 2-year history of diarrhea described as multiple bowel movements per day with urgency. Associated symptoms included fluctuating weight, abdominal pain, nausea, and painful hematochezia. Symptoms were exacerbated by certain foods and improved with a restrictive diet. She was otherwise healthy, had no prior antibiotic exposure, was without allergies, and had a travel history of 1 day in Mexico.
    CME Quiz

Reviews and Perspectives

    Reviews in Basic and Clinical Gastroenterology and Hepatology

    • Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs

      • Ingvar Bjarnason,
      • Carmelo Scarpignato,
      • Erik Holmgren,
      • Michael Olszewski,
      • Kim D. Rainsford,
      • Angel Lanas
      Published online: December 05, 2017
      Nonsteroidal anti-inflammatory drugs (NSAIDs) can damage the gastrointestinal tract, causing widespread morbidity and mortality. Although mechanisms of damage involve the activities of prostaglandin-endoperoxide synthase 1 (PTGS1 or cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review the mechanisms of gastrointestinal damage induction by NSAIDs via COX-mediated and COX-independent processes. NSAIDs interact with phospholipids and uncouple mitochondrial oxidative phosphorylation, which initiates biochemical changes that impair function of the gastrointestinal barrier.

Original Research

Continuing Medical Education (CME)/MOC Activities

Special Reports

  • Functional Bowel Disorders: A Roadmap to Guide the Next Generation of Research

    • Lin Chang,
    • Carlo Di Lorenzo,
    • Gianrico Farrugia,
    • ...
    • Gary M. Mawe,
    • Pankaj J. Pasricha,
    • John W. Wiley
    Published online: December 27, 2017
    In June 2016, the National Institutes of Health hosted a workshop on functional bowel disorders (FBDs), particularly irritable bowel syndrome, with the objective of elucidating gaps in current knowledge and recommending strategies to address these gaps. The workshop aimed to provide a roadmap to help strategically guide research efforts during the next decade. Attendees were a diverse group of internationally recognized leaders in basic and clinical FBD research. This document summarizes the results of their deliberations, including the following general conclusions and recommendations.
  • Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations

    • Denis Hadjiliadis,
    • Alexander Khoruts,
    • Ann G. Zauber,
    • ...
    • Patrick Maisonneuve,
    • Albert B. Lowenfels
    • on behalf of the Cystic Fibrosis Colorectal Cancer Screening Task Force
    Published online: December 28, 2017
    Improved therapy has substantially increased survival of persons with cystic fibrosis (CF). But the risk of colorectal cancer (CRC) in adults with CF is 5−10 times greater compared to the general population, and 25−30 times greater in CF patients after an organ transplantation. To address this risk, the CF Foundation convened a multi-stakeholder task force to develop CRC screening recommendations.
    Online ExtraVideo AbstractAdditional Online Content Available

Selected Summaries

  • And Now, Death by Proton Pump Inhibitor?

    • Michael Dougherty,
    • Evan S. Dellon
    Published online: January 11, 2018
    Xie Y, Bowe B, Li T, et al. Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open 2017:7e015735.
  • Just the FRAX: Management of Glucocorticoid-Induced Osteoporosis

    • Beth Wallace,
    • Kenneth G. Saag,
    • Jeffrey R. Curtis,
    • Akbar K. Waljee
    Published online: January 11, 2018
    Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arth Care Res 2017;69:1521–1537.
    • Carmen I. Gonzalez Keelan
    Published online: January 16, 2018
    As the prologue to the first edition of Sternberg’s Surgical Pathology states, the surgical pathologist’s career can be very lonely. Our working environment is characterized by our relationship with our microscopes, our books becoming companions in distress. Nowadays, the Internet and Google’s engines have entered the panorama, assisting in keeping abreast of the latest news in this era of knowledge explosion. Although Google can be helpful in finding new and old entities as well as pictures and references, the added value of this textbook relies on the reasoning process when approaching a differential diagnosis, as well as in the comprehensive summary of the immunohistochemistry (IHC) and molecular findings to be considered in the differential diagnosis.