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April 2020

Volume 158Issue 5p1179-1514, e1-e20

In Memoriam

  • In Memoriam: Sidney F. Phillips, MD

    • Michael Camilleri,
    • Adil E. Bharucha,
    • Patrick S. Kamath
    Published in issue: April 2020
    p1179-1181
    With saddened hearts, we share the passing of Dr Sidney F. Phillips, the Karl F. and Marjory Hasselmann Professor of Research and Consultant in Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota. Dr Phillips died on November 9, 2019, in St. Paul, Minnesota. We also celebrate the achievements and humanistic qualities of our mentor.

Covering the Cover

  • Covering the Cover

    • Andrew T. Chan,
    • Christopher S. Williams
    Published online: March 04, 2020
    p1182-1184
    A polygenic risk score derived from a large-scale genome-wide association study is associated with the risk of colorectal cancer, particularly among younger individuals.

Commentaries

  • Challenges With Stopping Long-term Nucleos(t)ide Analogue Therapy in Patients With Chronic Hepatitis B

    • K. Seng Liem,
    • Adam J. Gehring,
    • Jordan J. Feld,
    • Harry L.A. Janssen
    Published online: December 03, 2019
    p1185-1190
    The treatment goals for patients with chronic hepatitis B include improving quality of life and decreasing the risk of liver disease-related complications. These aims can be achieved with nucleos(t)ide analogue (NUC) therapy, which largely prevents liver failure, decreases the risk of hepatocellular carcinoma, and has excellent safety data.1,2 Yet low rates of on-therapy functional cure (hepatitis B surface antigen [HBsAg] loss), which is regarded as the optimal end point to withdraw therapy, preclude many patients from stopping therapy.
  • Incidence of Colorectal Cancer Matters

    • Robin B. Mendelsohn,
    • Sidney J. Winawer,
    • Dennis J. Ahnen
    Published online: December 18, 2019
    p1191-1195
    In the United States population ≥ 50 years old, both the incidence and mortality from colorectal cancer (CRC) has decreased by >50% in the last 40 years. Although CRC mortality has decreased dramatically in many developed countries (Figure 1), the United States is the only country with such a dramatic decrease in incidence (Figure 2). It has been estimated that more than one-half of this decrease in CRC incidence and mortality is due to CRC screening.1 Although there are multiple effective screening tests, their sensitivity for the detection of precancerous polyps varies substantially (Table 1).
  • Election of Anil Rustgi and Raymond DuBois to the National Academy of Medicine

    • Douglas E. Corley,
    • Richard M. Peek Jr.
    Published online: March 03, 2020
    p1196
    It is our honor and privilege at Gastroenterology to recognize and congratulate Drs Anil Rustgi and Ray DuBois on their richly deserved election into the National Academy of Medicine. Founded in 1970 as the Institute of Medicine (IOM), the National Academy of Medicine (NAM) is one of three academies that make up the National Academies of Sciences, Engineering, and Medicine the (the National Academies) in the United States. Operating under the 1863 Congressional charter of the National Academy of Sciences, the National Academies are private, nonprofit institutions that work outside of government to provide objective advice on matters of science, technology, and health.

Meeting Summary

  • Combating Gastric Cancer in Alaska Native People: An Expert and Community Symposium

    • Leisha D. Nolen,
    • Stephen M. Vindigni,
    • Julie Parsonnet
    • and the Symposium leaders
    Published online: December 10, 2019
    p1197-1201
    Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other US populations.1,2 Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and more frequently shows signet-ring or diffuse histology.3 It is known that the prevalence of Helicobacter pylori infection, a risk factor for gastric cancer, is high in AN people4; however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex.

Mentoring, Education, and Training Corner

  • How to Set Up a Successful Motility Lab

    • Rena Yadlapati,
    • Joan W. Chen,
    • Abraham Khan
    Published online: January 23, 2020
    p1202-1210
    Gastrointestinal (GI) motility disorders account for nearly one-half of outpatient gastroenterology visits, and motility tests are widely utilized to assess a multitude of chronic GI complaints.1 Fortunately, advancements in motility technologies and diagnostic concepts have enhanced the ability to characterize physiology and function across this prevalent patient population. Along the same lines, there is a growing trend of motility subspecialization among gastroenterologists and surgeons. In response to market demands, motility labs are increasingly initiated and grown.

Editorials

  • What’s App with GERD?

    • John M. Inadomi
    Published online: January 28, 2020
    p1211-1212
    The prevalence of gastroesophageal reflux disease (GERD) has been previously estimated in population-based studies to be in the range of 16%–28%.1,2 However, time trends in diet, obesity, and the racial and ethnic composition of the US population may have resulted in changes in the current prevalence of GERD. The investigators in this study3 obtained information from a large number of individuals across the United States using a mobile application designed to elicit eight major gastrointestinal symptom categories, including (1) heartburn, acid reflux, or gastroesophageal reflux, (2) abdominal pain, (3) bloating/gas, (4) constipation, (5) diarrhea, (6) disrupted swallowing, (7) fecal incontinence, and (8) nausea and vomiting.
  • Are the Rome Criteria a Sound Standard for Gastrointestinal Disorders Worldwide?

    • QiQi Zhou,
    • G. Nicholas Verne
    Published online: February 13, 2020
    p1212-1214
    Functional bowel disorders (FBDs) are the most common set of gastrointestinal disorders and include a variety of symptoms including diarrhea, constipation, abdominal pain, and bloating and distension. The etiology of FBDs remains largely unknown and there are currently no phenotypic markers or biochemical abnormalities to clearly define the disorders, leaving only symptom patterns as a method of diagnosis. A recent workshop on FBDs sponsored by the National Institutes of Health in 2016 highlighted the need for further investigation that includes emerging technologies such epigenomics, proteomics, and metabolomics to develop new diagnostic and treatment paradigms that could be applied to FBDs.
  • Cancer-Related Venous Thromboembolism as a Complication and Negative Prognostic Factor

    • Razmik Ghukasyan,
    • Timothy R. Donahue
    Published online: February 13, 2020
    p1214-1215
    The link between cancer and venous thromboembolism (VTE) has been explored since the nineteenth century, when it was first described by French internist Armand Trousseau.1 In the following decades, extensive research identified the multifactorial nature of the pathophysiology of cancer-associated hypercoagulability, which is explained by leukocytosis, thrombocytosis, increased circulation of tissue factor, and inflammatory cytokines.1 For many years, VTE has been viewed as a sequela of cancer, and its prognostic value not appreciated until recently.
  • Pancreatic Cancer Thrives on Hijacking a Homeostatic Tissue Repair Pathway

    • Yuliya Pylayeva-Gupta
    Published online: February 10, 2020
    p1216-1218
    Pancreatic ductal adenocarcinoma (PDAC) is one of most challenging tumor types and ranks as the third leading cause of cancer-related deaths in the United States.1 The patient presentation is typically at the late, often inoperable stage. Low sensitivity to chemotherapy and immunotherapeutic regiments are major challenges and have fostered diverse research efforts into diagnostic space and interference with Kras-driven oncogenic circuits, Kras being the oncogene most frequently altered in PDAC.2 In addition, many research studies have shown that inflammation and PDAC go hand in hand and contribute to seemingly all aspects of PDAC pathology, from inception of Kras-driven initiation of neoplasia, to establishment of cancer-sustaining stromal reaction, to potentiation of metastatic outgrowth.

Gastroenterology in Motion

Clinical Challenges and Images in GI

  • Unusual Calcified Lesions of the Liver and Lung in a Young Woman

    • Thierry Thévenot,
    • Céline Charon-Barra,
    • Paul Calame
    Published online: January 13, 2020
    p1222-1223
    Question: A previously healthy 35-year-old woman was referred to our outpatient department for an incidental finding of multifocal lesions disseminated in both hepatic lobes on an ultrasound examination initially performed for lombalgia. She took no medications, smoked 20 cigarettes a day, and drank no alcohol. The physical examination was unremarkable and she had no signs of chronic liver disease or hepatomegaly. She had a good appetite and denied weight loss or pulmonary symptoms.
  • An Unusual Case of Chronic Cough Revealing Ulcerative Colitis

    • Nassim Hammoudi,
    • Louise Bondeelle,
    • Jean-Marc Gornet
    Published online: January 13, 2020
    p1224-1225
    Question: A 22-year-old nonsmoking woman with no personal or familial medical history presented a daily productive cough over several months. She was treated with multiple empirical antibiotic therapy with transient improvement. Subsequently, she developed bloody diarrhea, diffuse abdominal pain, and a 5-kg weight loss. A colonoscopy revealed a nonulcerated pancolitis in a continuous fashion. Biopsy specimens revealed distorted crypt architecture with crypt branching and a diffuse inflammatory infiltrate composed of lymphocytes, plasma cells predominantly observed between the base of the crypts, and the muscularis mucosae and neutrophils, causing cryptitis.

Electronic Clinical Challenges and Images in GI

  • Abnormal Biliary Mucosa Uncovered in a Familial Adenomatous Polyposis Patient

    • Ravi S. Shah,
    • Thomas Plesec,
    • Amit Bhatt
    Published online: October 16, 2019
    e1-e2
    Question: A 36-year-old woman with familial adenomatous polyposis (FAP), status post proctocolectomy, pancreas-sparing duodenectomy for Spiegelman stage IV polyposis was found to have polyposis in the jejunum on surveillance capsule endoscopy. Physical examination and laboratory values were normal. Push enteroscopy revealed polyposis in the jejunum with a 15-mm polyp involving the biliojejunal anastomosis (Figure A). Given that this polyp was nonlifting, it was removed with hybrid endoscopic submucosal dissection.
    Online Only
  • Right Upper Quadrant Pain With Positive Murphy’s Sign in a 19-Year-Old Woman

    • Hiroki Matsuura,
    • Masayuki Kishida,
    • Waku Shimizu
    Published online: November 15, 2019
    e3-e4
    Question: A 19-year-old woman presented to our emergency department with acute abdominal pain, nausea, and vomiting. She had no previous medical history. She denied drug abuse, lead poisoning, allergies, abdominal injury, or psychiatric problems. She was febrile, but her vital signs were normal. On physical examination, she exhibited severe tenderness of the epigastrium with guarding and right upper quadrant pain with positive Murphy’s sign. Ultrasound examination and enhanced computed tomography scans were performed (Figure A, B, yellow arrow).
    Online Only
  • A Unique Case of Massive Colonic Distention

    • Jae Eun Lee,
    • Louisa Chiu,
    • Mimi C. Tan
    Published online: November 15, 2019
    e5-e6
    Question: A 61-year-old man with a history of alcohol abuse presented with 2 years of intermittent episodes of abdominal distention associated with abdominal pain, vomiting, and decreased bowel movements. Symptoms would spontaneously resolve after a few days with episodes of diarrhea immediately following. He has had 50 pounds of unintentional weight loss in the past 2 years owing to these symptoms. He presented during one of these episodes triggered by air travel with symptoms for 10 days before presentation.
    Online Only
  • Staying on Tract in a Patient With Right Upper Quadrant Pain and a Cholecystostomy Tube

    • Jade Law,
    • Alex Zhornitskiy,
    • James H. Tabibian
    Published online: November 15, 2019
    e7-e9
    Question: A 58-year-old woman presented to the emergency department with food intolerance attributed to nausea and pain at her percutaneous cholecystostomy drain site. Two weeks prior, she had been admitted to an outside hospital for severe right upper quadrant pain without nausea, vomiting, fevers, or chills. The workup at that time included abdominal imaging that was suggestive of cholecystitis and choledocholithiasis. Endoscopic retrograde cholangiography was performed, during which stones were extracted and nonfilling of the cystic duct was noted.
    Online Only
  • A Rare Cause of Difficult Endoscopic Retrograde Cholangiopancreatography

    • Khaldoon Khirfan
    Published online: November 15, 2019
    e10-e11
    Question: A 72-year-old female patient with history of morbid obesity and obstructive sleep apnea presented with epigastric abdominal pain, fever, confusion, and jaundice. Temperature was 38.8°C, blood pressure was 138/80 mm Hg, and heart rate was 98 bpm. The patient had minimal tenderness in the epigastric area on abdominal examination.
    Online Only
  • A Rare Association With Obstructive Jaundice

    • Verónica Pavão Borges,
    • Rui Alves,
    • João Coimbra
    Published online: November 15, 2019
    e12-e13
    Question: A 4-year-old boy was admitted for fever, vomiting, and abdominal pain. Physical examination showed tenderness and a palpable mass on the right upper quadrant. Laboratory studies revealed elevated white blood cell count (20.00 × 103/μL) and C-reactive protein levels (380 mg/L) and normal total serum bilirubin levels (0.64 mg/dL). Ultrasound examination of the abdomen showed dilatation of the common bile duct with a polyploid endoluminal mass (Figure A), dilated intrahepatic biliary channels, and parietal thickening of the gallbladder.
    Online Only

Practical Teaching Cases

  • The Key to a Boy’s Heart Is Through His Intestine

    • Amir Jazayeri,
    • Dieudonne Nonga,
    • Meenakshi Rao
    Published online: September 24, 2019
    p1226-1228
    Question: A 10-year-old male presented to clinic with three months of diarrhea, post-prandial abdominal pain, fevers, and 20lb weight loss. He was on no medications and had no history of travel or family history of gastrointestinal or autoimmune disorders. Laboratory testing was notable for markedly elevated inflammatory markers (ESR 96mm/hr, CRP 94 mg/L), hypoalbuminemia (2.8g/dL), Hgb 9.6 g/dL, and WBC count of 17.1x103/uL. Inflammatory bowel disease was high on the differential with an estimated PCDAI score of 57.
  • Getting to the Root of the Problem

    • Jennifer Wang,
    • Oliver S. Eng,
    • Dejan Micic
    Published online: September 24, 2019
    p1229-1231
    Question: A 52-year-old man presented with a 10-day duration of intermittent abdominal pain and 5-kg weight loss. Abdominal computed tomography (CT) revealed a lobulated 4.3 x 2.1 x 4 cm hyperdense mass within the mesentery at the level of the superior mesenteric vein (SMV) (Figure A). There were multiple branches of the superior mesenteric artery (SMA) coursing through the mass. In addition, there was thrombosis of the SMV and portal vein. The liver and pancreas appeared normal. Laboratory tests showed normal levels of chromogranin A, plasma serotonin, IgG4, and lactate dehydrogenase.
    CME Quiz

Reviews and Perspectives

    Reviews in Basic and Clinical Gastroenterology and Hepatology

    • Mechanisms, Evaluation, and Management of Chronic Constipation

      • Adil E. Bharucha,
      • Brian E. Lacy
      Published online: January 13, 2020
      p1232-1249.e3
      With a worldwide prevalence of 15%, chronic constipation is one of the most frequent gastrointestinal diagnoses made in ambulatory medicine clinics, and is a common source cause for referrals to gastroenterologists and colorectal surgeons in the United States. Symptoms vary among patients; straining, incomplete evacuation, and a sense of anorectal blockage are just as important as decreased stool frequency. Chronic constipation is either a primary disorder (such as normal transit, slow transit, or defecatory disorders) or a secondary one (due to medications or, in rare cases, anatomic alterations).
      Online ExtraAdditional Online Content Available

Original Research

Continuing Medical Education (CME)/MOC Activities

Clinical Practice Guidelines

  • AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis

    • Joseph D. Feuerstein,
    • Kim L. Isaacs,
    • Yecheskel Schneider,
    • ...
    • Yngve Falck-Ytter,
    • Siddharth Singh
    • on behalf of the AGA Institute Clinical Guidelines Committee
    Published online: January 13, 2020
    p1450-1461
    This document presents the official recommendations of the American Gastroenterological Association (AGA) on the management of moderate to severe ulcerative colitis (UC). The guideline was developed by the AGA Institute’s Clinical Guidelines Committee and approved by the AGA Governing Board. It is accompanied by a technical review that provides a detailed synthesis of the evidence from which these recommendations were formulated.1 Development of this guideline and the accompanying technical review was fully funded by the AGA Institute without additional outside funding.
  • Pharmacological Management of Adult Outpatients With Moderate to Severely Active Ulcerative Colitis

    • American Gastroenterological Association
    Published online: March 11, 2020
    p1462-1463
  • Spotlight: Management of Moderate-to-Severe Ulcerative Colitis

    • Joseph D. Feuerstein,
    • Kim L. Isaacs,
    • Yecheskel Schneider,
    • ...
    • Yngve Falck-Ytter,
    • Siddharth Singh
    • on behalf of the American Gastroenterological Association Institute Clinical Guidelines Committee
    Published online: March 10, 2020
    p1464
  • AGA Technical Review on the Management of Moderate to Severe Ulcerative Colitis

    • Siddharth Singh,
    • Jessica R. Allegretti,
    • Shazia Mehmood Siddique,
    • Jonathan P. Terdiman
    Published online: January 13, 2020
    p1465-1496.e17
    A subset of patients with ulcerative colitis (UC) present with, or progress to, moderate to severe disease activity. These patients are at high risk for colectomy, hospitalization, corticosteroid dependence, and serious infections. The risk of life-threatening complications and emergency colectomy is particularly high among those patients hospitalized with acute severe ulcerative colitis. Optimal management of outpatients or inpatients with moderate to severe UC often requires the use of immunomodulator and/or biologic therapies, including thiopurines, methotrexate, cyclosporine, tacrolimus, TNF-α antagonists, vedolizumab, tofacitnib, or ustekinumab, either as monotherapy or in combination (with immunomodulators), to mitigate these risks.
    Online ExtraAdditional Online Content Available

Brief Communications

  • Most Patients With Celiac Disease on Gluten-Free Diets Consume Measurable Amounts of Gluten

    • Jocelyn A. Silvester,
    • Isabel Comino,
    • Ciarán P. Kelly,
    • Carolina Sousa,
    • Donald R. Duerksen
    • on behalf of the DOGGIE BAG Study Group
    Published online: December 19, 2019
    p1497-1499.e1
    A gluten-free diet (GFD) is the primary treatment for celiac disease (CD), yet many have persistent villous atrophy despite following a strict GFD. Several lines of indirect evidence suggest that persistent villous atrophy reflects ongoing gluten exposure; however, only recently have tools become available to test this hypothesis directly.
    Online ExtraAdditional Online Content Available
  • Identification and Characterization of Unique Neutralizing Antibodies to Mouse EGF Receptor

    • Won Jae Huh,
    • Hiroaki Niitsu,
    • Brandon Carney,
    • Eliot T. McKinley,
    • Jacob L. Houghton,
    • Robert J. Coffey
    Published online: December 19, 2019
    p1500-1502
    Open Access
    The epidermal growth factor (EGF) receptor (EGFR) neutralizing monoclonal antibody (mAb) cetuximab is approved by the US Food and Drug Administration for the treatment of advanced colorectal cancer (CRC) and head and neck squamous cell carcinoma, whereas EGFR tyrosine kinase inhibitors are ineffective.1 Efforts to use EGFR mAb therapy in mouse models of colon cancer have been stymied by the lack of neutralizing mAbs to mouse EGFR. MM-151 is a combination of 3 anti-EGFR mAbs (P1X, P2X, and P3X) shown to have greater receptor down-regulation, immune-effector function, and antiproliferative activity than cetuximab; MM-151 is also able to overcome cetuximab resistance in patients with CRC whose tumors harbor mutations in the extracellular domain (ED) of EGFR, which is divided into ED1–4.
    Additional Online Content Available
  • Recent Decline in Hepatocellular Carcinoma Rates in the United States

    • Meredith S. Shiels,
    • Thomas R. O’Brien
    Published online: January 18, 2020
    p1503-1505.e2
    Open Access
    In the United States, hepatocellular carcinoma (HCC), a highly lethal cancer with limited treatment options, is primarily caused by chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH), and excessive alcohol consumption.1 HCC development generally requires decades-long exposure to 1 or more risk factors.
    Online ExtraAdditional Online Content Available

Selected Summaries

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