VOL. 12 NO. 3 MARCH 2018

®

Many drugs in the INSIDE IBD AND INTESTINAL pipeline for IBD DISORDERS High BMI linked to problems in IBD treatment Obesity related to ews

n increased rate of BY DOUG BRUNK sentation by highlighting

ical hospitalization. • 23

eD Frontline Medical News anti-integrin therapies for inflammatory bowel LIVER DISEASE LAS VEGAS – A wide disease (IBD) treatment. Obesity affects the variety of drugs are in These leukocyte membrane ability to diagnose the pipeline for both ul- glycoproteins target beta1 runk /F rontline M cerative colitis (UC) and and beta7 subunits. They liver fibrosis

oug B As BMI increases, so does

D Crohn’s disease patients interact with endothelial li- Dr. Kenneth Cusi said, “Patients with diabetes [type 2] face the who are failing currently gands VCAM-1, fibronectin, discordance between greatest risk of fatty liver and of fibrosis.” available therapies. and MadCAM-1, and medi- imaging techniques. • 32 “The challenge for all ate leukocyte adhesion and GI ONCOLOGY of us is to integrate the trafficking. Approved an- Circulating tumor cell Three in 10 diabetic right drugs for the right ti-integrin therapies to date patients,” William J. Sand- include natalizumab and assay for CRC born, MD, AGAF, said at vedolizumab, while inves- High sensitivity and patients may have the annual congress of the tigational therapies include specificity reported. • 38 Crohn’s & Colitis Founda- etrolizumab, PF-00547659, tion, a partnership of the abrilumab, and AJM 300. AGA GUIDELINE liver fibrosis Crohn’s & Colitis Foun- In a phase 2 study of Use goal-directed dation and the American etrolizumab as induction fluid therapy, early BY DOUG BRUNK to treat it,” he said at the Gastroenterological Asso- therapy for moderate to se- refeeding in acute Frontline Medical News World Congress on Insulin ciation. vere UC, Séverine Vermeire, pancreatitis Resistance, Diabetes & Car- Dr. Sandborn, professor MD, AGAF, Dr. Sandborn, Recommendations for LOS ANGELES – For every diovascular Disease. and chief of the division and associates randomized the first 2 weeks of 10 adult patients with type Dr. Cusi, chief of the di- of gastroenterology at the 124 patients to one of two treatment. • 39 2 diabetes, three are likely vision of endocrinology, University of California, dose levels of subcutane- to have moderate to severe diabetes, and metabolism San Diego, began his pre- See Pipeline · page 22 liver fibrosis, according to at the University of Florida, Kenneth Cusi, MD, FACP, Gainesville, predicted that FACE. obesity will become the No. New multi-analyte blood test shows “The question is, How 1 cause of liver transplan- are we going to tackle this tation. “It’s a real epidemic; problem? My academic you’re not seeing it because promise screening for several cancers goal is that we incorporate the inflexion of obesity hap- screening for NASH [non- pened just 2 decades ago,” BY SHANNON AYMES cancer types. 99% in a cohort of 1,005 alcoholic steatohepatitis], he said. “Patients with dia- Frontline Medical News It’s early days for the patients with stage I-III or for fibrosis more spe- betes face the greatest risk technology, called Cancer- cancers and 850 healthy cifically, in the same way of fatty liver and of fibrosis. magine a single blood SEEK, but the test had a controls, wrote Joshua D. we do for retinopathy or Untreated, it’s the equiva- I test that would cost sensitivity of 69%-98%, Cohen of the Ludwig Cen- nephropathy [in diabetes], lent of having macroalbu- less than $500 and could depending on the cancer ter for Cancer Genetics and because we do have a way See Fibrosis · page 25 screen for at least eight type, and a specificity of See Blood test · page 34

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LETTER FROM THE EDITOR: IBD drugs, ‘liquid biopsies,’ and DDW

he coming months will provide us welcome sponses. We are entering at concentrations that are vanishingly low. These relief from health care politics as we turn an era of precision medi- methodologies may allow screening for digestive T our attention to the science of medicine. Di- cine never before seen in cancers using blood and stool testing at accuracy gestive Disease Week® (DDW) will be in Washing- our specialty. Most of these rates that rival endoscopy – and at reduced cost. ton, D.C. from June 2 to 5. Major themes already biological medications can Other themes that we will see emphasized at are emerging and implications for our clinical be given orally or subcu- DDW® include the microbiome, telehealth, pre- practices are exciting. In this month’s issue of GI taneously, precluding the cision health, and use of “big data” for predictive & Hepatology News we summarize a presenta- need for infusion centers. analysis and risk stratification of patients. tion about the IBD medication pipeline given by I anticipate an enormous The Board of Editors appreciates the feedback Dr. Bill Sandborn (UCSD) at the Crohn’s & Colitis offering of IBD-related sci- that many of you sent us in our latest readership CongressTM (a partnership between the Crohn’s ence at DDW®. survey. Each month, we try hard to collect articles & Colitis Foundation and AGA in Las Vegas). The DR. ALLEN Two other articles this of clinical interest to the wide variety of clinicians number of medications that will enter clinical month should be read and researchers that read GI & Hepatology News. practice is impressive. Over the last several de- carefully. “Liquid biopsies” are coming. We know We will continue to improve our offerings based on cades, we have defined multiple inflammatory that solid cancers shed DNA into the circulation. your valuable opinions. pathways that can lead to IBD and developed We now have molecular tools to identify circulat- John I. Allen, MD, MBA, AGAF medications that modify abnormal immune re- ing tumor-related epigenetic and DNA changes Editor in Chief

Quick Quiz Q2. A 68-year-old woman with further options to treat her pain. alcoholic chronic pancreatitis epigastrum, but otherwise it is un- has constant, disabling pain. She Which intervention will most likely Q1. A 37-year-old man with no remarkable. A complete blood count has previously tried gabapentin, improve her pain and quality of life significant past medical history reveals a white blood cell count of 6, celecoxib, and antioxidants with over the next 5 years? presents with a dull, nonradiating hemoglobin 10 g/dL, MCV 72 fL, and some improvement. She currently A. Continued medical therapy and in- epigastric pain for 3 months. The platelet count of 200 x 103/mcL. takes nonenteric coated pancre- creased dose of pancreatic enzymes pain is not associated with eating or alipase (90,000 IU per meal) and B. Lateral pancreaticojejunostomy positional changes. He denies any What is the most important next controlled-release oxycontin. CT (Peustow procedure) heartburn, regurgitation, chest pain, step of management? of the abdomen shows a few small C. ERCP with lithotripsy and stent nausea, vomiting, dysphagia, odyno- A. Schedule an abdominal ultra- punctate calcifications in the head placement phagia, or weight loss. He currently sound of the pancreas, a 1-cm calculus in D. EUS-guided celiac plexus block does not take any medications. Fam- B. Send an H. pylori stool antigen the genu with a markedly dilated E. Total pancreatectomy with islet ily history is not significant. Phys- C. Schedule an upper endoscopy pancreatic duct in the body and tail, autotransplantation ical examination reveals minimal D. Empiric antisecretory therapy and moderate distal atrophy. There tenderness to deep palpation in the E. Start amitriptyline 25 mg daily are no pseudocysts. She discusses The answers are on page 32.

Editor in ChiEf Gi & hEpAtoloGy nEws is the official newspaper of the American frontlinE mEdiCAl CommuniCAtions soCiEty pArtnErs John I. Allen, MD, MBA, AGAF Gastroenterological Association (AGA) Institute and provides the VP/Group Publisher; Director, FMC Society Partners Mark Branca AssoCiAtE Editors gastroenterologist with timely and relevant news and commentary about Editor in Chief Mary Jo M. Dales clinical developments and about the impact of health care policy. Content for Megan A. Adams, MD, JD, MSc Executive Editors Denise Fulton, Kathy Scarbeck Gi & hEpAtoloGy nEws is developed through a partnership of the newspaper’s Editor Lora T. McGlade Ziad Gellad, MD, MPH, AGAF medical board of editors (Editor in Chief and Associate Editors), Frontline Kim L. Isaacs, MD, PhD, AGAF Creative Director Louise A. Koenig Medical Communications Inc. and the AGA Institute Staff. “News from the Bryson Katona, MD, PhD AGA” is provided exclusively by the AGA, AGA Institute, and AGA Research Director, Production/Manufacturing Rebecca Slebodnik Gyanprakash A. Ketwaroo, MD, MSc Foundation. All content is reviewed by the medical board of editors for National Account Manager Artie Krivopal, 973-206-2326, Larry R. Kosinski, MD, MBA, AGAF accuracy, timeliness, and pertinence. To add clarity and context to important cell 973-202-5402, [email protected] Sonia S. Kupfer, MD developments in the field, select content is reviewed by and commented on by Digital Account Manager Rey Valdivia, 973-206-8094, Wajahat Mehal, MD, PhD external experts selected by the board of editors. [email protected] Senior Director of Classified Sales Tim LaPella, 484-921-5001, [email protected] Editors EmEritus The ideas and opinions expressed in Gi & hEpAtoloGy nEws do not Colin W. Howden, MD, AGAF necessarily reflect those of the AGA Institute or the Publisher. The AGA Advertising Offices 7 Century Drive, Suite 302, Parsippany, NJ 07054-4609 973-206-3434, fax 973-206-9378 Charles J. Lightdale, MD, AGAF Institute and Frontline Medical Communications Inc. will not assume MEDICAL COMMUNICATIONS AGA institutE stAff responsibility for damages, loss, or claims of any kind arising from or related FRONTLINE to the information contained in this publication, including any claims related Vice President, Marketing & Customer Managing Editor Brook A. Simpson to the products, drugs, or services mentioned herein. Advertisements do Chairman Stephen Stoneburn President/CEO Alan J. Imhoff Advocacy Jim McDonough Special Content Editor Lindsey M. Brounstein not constitute endorsement of products on the part of the AGA Institute or CFO Douglas E. Grose Vice President, Operations Jim Chicca Senior Publications Coordinator Jillian L. Schweitzer Frontline Medical Communications Inc. Vice President, Sales Mike Guire Vice President of Publications Erin C. Landis President, Digital Douglas E. Grose Vice President, Society Partners Chief Digital Officer Lee Schweizer offiCErs of thE AGA institutE POSTMASTER Send changes of address (with old mailing Mark Branca Vice President, Digital Publishing Circulation Director Jared Sonners President Sheila E. Crowe, MD, AGAF label) to GI & Hepatology News, Subscription Service, 151 Amy Pfeiffer Corporate Director, Research & Fairchild Ave., Suite 2, Plainview, NY 11803-1709. President-Elect David A. Lieberman, MD, AGAF President, Custom Solutions JoAnn Wahl Communications Lori Raskin Editor in Chief Mary Jo M. Dales Vice President Hashem B. El-Serag, MD, MPH, AGAF The AGA Institute headquarters is located at 4930 Del Ray Vice President, Custom Programs Secretary/Treasurer Francis M. Giardiello, MD, AGAF Avenue, Bethesda, MD 20814, [email protected]. Carol Nathan Editorial Offices 2275 Research Blvd, Suite 400, Rockville, MD Vice President, Custom Solutions Wendy In affiliation with Global Academy for Raupers Medical Education, LLC ©2018 by the AGA Institute. All rights reserved. No part of this publication 20850, 240-221-2400, fax 240-221-2548 Scan this QR Code to visit may be reproduced or transmitted in any form or by any means, electronic or Gi & hEpAtoloGy nEws Senior Vice President, Finance Vice President, Medical Education & (ISSN 1934-3450) is published monthly for gihepnews.com mechanical, including photocopy, recording, or any information storage and Steven J. Resnick Conferences Sylvia H. Reitman, MBA $230.00 per year by Frontline Medical Communications Inc., Vice President, Human Resources & retrieval system, without permission in writing from the publisher. 7 Century Drive, Suite 302, Parsippany, NJ 07054-4609. Vice President, Events David J. Small, Facility Operations Carolyn Caccavelli MBA Phone 973-206-3434, fax 973-206-9378 GIHEPNEWS.COM • MARCH 2018 NEWS 7 FROM THE AGA JOURNALS Engineered liver models to study human hepatotropic pathogens

BY CHHAVI JAIN Cellular and Molecular Gastroenter- gens, however, maintaining these pathogens such as Ebola, Lassa, Frontline Medical News ology and Hepatology (2018;5:131- cells ex vivo is challenging. human cytomegalovirus, and den- 44), described these unique models. For instance, 2-D monolayers gue viruses; and to generate virion ecently, exciting clinical prog- Furthermore, the progress made in of human hepatoma-derived cell stocks (HCV, HBV). For long-term ress has been made in the combining individual approaches scientific analyses and cultures, as R study of hepatotropic patho- and pairing the most appropriate well as clinical isolates of pathogens gens in the context of liver-depen- model system and readout modality Tissue engineering has been that do not infect hepatoma cells, dent infectious diseases. Tissue was discussed. immortalized cell lines have been engineering has been applied to au- The major human hepatotropic applied to authentically engineered to differentiate and thentically recapitulate human liver pathogens include hepatitis C virus recapitulate human liver biology, maintain HH functions for a longer biology, facilitating the study of (HCV), hepatitis B virus (HBV), and duration. Additionally, cocultivation host-pathogen interactions during the protozoan parasites Plasmodi- facilitating the study of host- of primary hepatocytes with non- the entire pathogen life cycle. This um falciparum and P. vivax. While pathogen interactions during parenchymal cells or hepatocytes is crucial for the development and HBV and HCV can cause chronic the entire pathogen life cycle. with mouse fibroblasts preserves validation of therapeutic interven- liver diseases such as cirrhosis and hepatocyte phenotype. The latter is tions, such as drug and vaccine hepatocellular carcinoma, Plasmodi- a self-assembling coculture system candidates that may act on the um parasites cause malaria. The use that could potentially maintain an liver cells. The engineered models of cancer cell lines and animal mod- lines (such as HepG2-A16 and infection for over 30 days and be range from two-dimensional (2-D) els to study host-pathogen inter- HepaRG) are easier to maintain, used for testing anti-HBV drugs. A cultures of primary human hepato- actions is limited by uncontrolled to amplify for scaling up, and to micropatterned coculture system, cytes (HH) and stem cell–derived proliferation, abnormal liver-spe- use for drug screening, thus repre- in which hepatocytes are positioned progeny to three-dimensional (3-D) cific functions, and stringent host senting a renewable alternative to in “islands” via photolithographic organoid cultures and humanized dependency of the hepatotropic primary hepatocytes. These model patterning of collagen, surrounded rodent models. A review by Nil pathogens. HHs are thus the only systems have been useful to study by mouse embryonic fibroblasts, Gural and colleagues, published in ideal system to study these patho- short-term infections of human can maintain hepatocyte pheno- Plasmodium parasites (P. vivax and types for 4-6 weeks, and remain P. falciparum); other hepatotropic Continued on following page ural et al. present a timely and From the discussions of various G outstanding review of the ad- studies, it is clear that this field vances made in the engineering has benefitted tremendously from of human-relevant liver advances in tissue engi- June 2–5, 2018 Exhibit Dates: June 3–5 culture platforms for in- neering, including micro- Walter E. Washington vestigating the molecular fabrication tools adapted Convention Center mechanisms of infectious from the semiconductor Washington, DC diseases (e.g., hepatitis industry, to construct hu- www.ddw.org B/C viruses and Plasmo- man liver platforms that dium parasites that cause last for several weeks malaria) and developing in vitro, can be infected Monumental Developments better drugs or vaccines with hepatitis B/C virus in Science & Medicine against such diseases. and Plasmodium para- The authors cover a con- DR. KHETANI sites with high efficien- Washington, DC tinuum of platforms with cies, and are very useful increasing physiological complexity, for high-throughput and high-con- such as 2-D hepatocyte monocul- tent drug screening applications. tures on collagen-coated plastic, The latest protocols in isolating and Register online at 2-D cocultures of hepatocytes and cryopreserving primary human he- www.ddw.org/registration nonparenchymal cells, (both ran- patocytes and differentiating stem domly distributed and patterned cells into hepatocyte-like cells with into microdomains to optimize adult functions help reduce the Discover monumental cell-cell contact), 3-D cultures/ reliance on abnormal or cancerous developments in science and cocultures housed in biomateri- cell lines for building platforms medicine at Digestive Disease al-based scaffolds, perfusion-based with higher relevance to the clinic. Week® (DDW) 2018. DDW bioreactors to induce cell growth Ultimately, continued advances in generates and shares capital ideas for global impact and phenotypic stability, and finally microfabricated human liver plat- in the fi elds of rodents with humanized livers. Cell forms can aid our understanding gastroenterology, REGISTER BY APRIL 18 AND SAVE AT LEAST $80. hepatology, GI sourcing considerations for build- of liver infections and spur further Jan. 17, 2018 AASLD, AGA, ASGE and SSAT ing human-relevant platforms are drug/vaccine development. endoscopy members-only registration opens. discussed, including cancerous cell and GI surgery. Jan. 24, 2018 General registration opens. Attend DDW 2018 lines, primary human hepatocytes, Salman R. Khetani, PhD, is associate in Washington, DC. DDW On Demand is Included and stem cell–derived hepatocytes professor, department of bioengineer- with Registration! Get access to the online digital (e.g., induced pluripotent stem ing, University of Illinois at Chicago. presentations from DDW 2018 so . cells). He has no conflicts of interest. you don’t miss a single session. 8 NEWS MARCH 2018 • GI & HEPATOLOGY NEWS FROM THE AGA JOURNALS Model supports endoscopic resection for some T1b esophageal adenocarcinomas

BY AMY KARON efficacy and cost efficacy of the two approaches sistent, and the model did not test whether high Frontline Medical News in hypothetical T1a and T1b patients of various versus low pathologic risk affected treatment ages and comorbidities, using cancer death data preference, the researchers said. They added ndoscopic treatment of T1a esophageal ad- from the Surveillance, Epidemiology, and End data on T1NOS (T1 not otherwise specified) enocarcinoma outperformed esophagecto- Results (SEER) Medicare database and published EACs to the model because the SEER-Medicare E my across a range of ages and comorbidity cost data converted to 2017 U.S. dollars based levels in a Markov model. on the U.S. Bureau of Labor Statistics’ Consumer Esophagectomy produced 0.16 more unadjust- Price Index. ‘[If] a patient considered his or her ed life-years, but led to 0.27 fewer quality-ad- Like the T1a case, the T1b base case consisted quality of life postesophagectomy justed life-years (QALYs), in the hypothetical of a 75-year-old man with a Charlson comor- case of a 75-year-old man with T1aN0M0 esoph- bidity index of 0. Esophagectomy produced nearly equal to, or preferable to, [that] ageal adenocarcinoma (EAC) and a Charlson co- 0.72 more unadjusted life years than did endo- postendoscopic treatment, esophagectomy morbidity index score of 0, reported Jacqueline scopic treatment (5.73 vs. 5.01) while yielding would be the optimal treatment N. Chu, MD, of Massachusetts General Hospital, 0.22 more QALYs (4.07 vs. 3.85, respectively). Boston, and her asso- Esophagectomy cost strategy,’ the investigators wrote. ciates. “[We] believe $156,981 more, but the QALYs are a more im- model did not account portant endpoint be- for costs of chemother- database included so few T1b endoscopic cases, cause of the significant apy and radiation or but T1NOS patients had the worst outcomes morbidity associated with esophagectomy,” they palliative care, all of which are more likely with and were in fact probably higher stage than T1. wrote in the March issue of Clinical Gastroenter- endoscopic resection than esophagectomy, the Fully 31% of endoscopy patients were T1NOS, ology and Hepatology. researchers noted. compared with only 11% of esophagectomy In contrast, the model portrayed the man- In sensitivity analyses, endoscopic treatment patients, which would have biased the model agement of T1b EAC as “an individualized deci- optimized quality of life in T1b EAC patients against endoscopic treatment, according to the sion” – esophagectomy was preferable in 60- to who were older than 80 years and had a comor- investigators. 70-year-old patients with T1b EAC, but serial bidity index of 1 or 2. Beyond that, treatment The National Institutes of Health provided endoscopic treatment was better when patients choice depended on posttreatment variables. funding. Dr. Chu reported having no conflicts were older, with more comorbidities, the re- “[If] a patient considered his or her quality of interest. Three coinvestigators disclosed ties searchers said. “For the sickest patients, those of life postesophagectomy nearly equal to, or to CSA Medical, Ninepoint, C2 Therapeutics, aged 80 and older with comorbidity index of 2, preferable to, [that] postendoscopic treatment, Medtronic, and Trio Medicines. The remaining endoscopic treatment not only provided more esophagectomy would be the optimal treatment coinvestigators had no conflicts. QALYs but more unadjusted life years as well.” strategy,” the investigators wrote. “An example Treatment of T1a EAC is transitioning from would be the patient who would rather have an [email protected] esophagectomy to serial endoscopic resection, esophagectomy than worry about recurrence which physicians still tend to regard as too risky with endoscopic treatment.” SOURCE: Chu JN et al. Clin Gastroenterol Hepatol. 2017 in T1b EAC. The Markov model evaluated the Pathologic analysis of T1a EACs can be incon- Nov 24. doi: 10.1016/j.cgh.2017.10.024.

Continued from previous page often lack the complexity of the liver sponges, matrigel, and collagen into Fah[-/-], Rag2[-/-], and Il2rg[-/-] microenvironment and impact of dif- have been developed and shown to mice with or without a nonobese permissive to P. falciparum, P. vivax, ferent cell types on liver infections. be permissive to HCV or HBV infec- diabetic background), and TK-NOG HBV, and HCV infections. Further- A 3-D radial-flow bioreactor (cylin- tions. Although 3-D coculture sys- (HHs transplanted into herpes sim- more, micropatterned coculture drical matrix) was able to maintain tems exhibit better hepatic function plex virus type-1 thymidine kinase systems support full developmental and differential gene expression pro- mice) were validated for HCV, HBV, P. liver stages of both P. falciparum files in comparison to 2-D counter- falciparum, and P. vivax infections. It and P. vivax, with the release of Recently, several liver-on-a- parts, they require a large quantity is, however, laborious to create and merozoites from hepatocytes and of cells and are a challenge to scale maintain chimeric mouse models and their subsequent infection of over- chip models have been created up. Recently, several liver-on-a-chip monitor infection processes in them. laid human red blood cells. that mimic shear stress, blood models have been created that mim- It is important to note that the Alternatively, embryonic stem cells ic shear stress, blood flow, and the selection of model system and the and induced pluripotent stem cells of flow, and the extracellular extracellular environment within a readout modality to monitor infec- human origin can be differentiated environment within a tissue. tissue, holding great potential for tion will vary based on the exper- into hepatocytelike cells that enable modeling liver-specific pathogens. imental question at hand. Tissue investigation of host genetics within Humanized mouse models with engineering has thus far made sig- the context of host-pathogen interac- and amplify human hepatoma cells ectopic human liver structures have nificant contributions to the knowl- tions, and can also be used for target (for example, Huh7 cells), by provid- been developed in which primary edge of hepatotropic pathogens; a identification for drug development. ing sufficient oxygen and nutrient HHs are transplanted following continued effort to develop better However, stem cell cultures require supply, supporting productive HCV liver injury. Chimeric mouse mod- liver models is envisioned. significant culture expertise and may infection for months. Other 3-D cul- els including Alb-uPA/SCID (HHs not represent a fully differentiated tures of hepatoma cells using poly- transplanted into urokinase-type [email protected] adult hepatocyte phenotype. ethylene glycol–based hydrogels, plasminogen activator-transgenic Although 2-D cultures offer ease of thermoreversible gelatin polymers, severe combined immunodeficient SOURCE: Gural N et al. Cell Mol Gas- use and monitoring of infection, they alginate, galactosylated cellulosic mice), FNRG/FRG (HHs transplanted tronterol Hepatol. 2018;5:131-44.). GIHEPNEWS.COM • MARCH 2018 NEWS 9 FROM THE AGA JOURNALS Sofosbuvir/ledipasvir safe in HBV coinfected patients

BY AMY KARON ment, the researchers wrote in the then every 12 weeks until post- ALT elevations, no patient had signs Frontline Medical News March issue of Gastroenterology. treatment week 108. of liver failure,” the researchers Because chronic hepatitis C virus In all, 70 (63%) patients devel- wrote. “Our results support the rec- or patients with chronic hep- infection tends to suppress HBV oped HBV reactivation, including ommendations put forth in clinical atitis C and hepatitis B virus replication, peginterferon/ribavirin 84% of the 37 patients with un- treatment guidelines: HCV-infected F (HBV) coinfection, 12 weeks or direct-acting anti-HCV treatment detectable HBV DNA at baseline. patients should be evaluated for of ledipasvir/sofosbuvir therapy can reactivate HBV infection, espe- During treatment, none of these HBV infection prior to HCV treat- achieved a 100% sustained viral cially in patients who test positive patients had ALT rise more than ment with direct-acting antivirals. response rate without causing liver for hepatitis B surface antigen (HB- twice the upper limit of normal. By Those who are HBsAg positive failure or death in a phase 3b, mul- sAg). Left untreated, reactivated 48 weeks post treatment, howev- should be monitored during and af- ticenter, open-label study. HBV can lead to fulminant hepatitis, er, 77% still had quantifiable HBV ter treatment for HBV reactivation, “Although we observed increas- liver failure, and death, as noted on DNA, and two had marked ALT and treatment should be initiated es in HBV DNA in most patients, recently mandated boxed warnings. rises. Furthermore, by posttreat- in accordance with existing guide- these increases were [usually] not Accordingly, guidelines recom- ment week 53, one of these patients lines.” associated with ALT [alanine amino mend testing patients for HBV developed bilirubinemia and symp- Gilead funded the study. Dr. Liu transferase] flares or clinical com- infection before starting HCV treat- tomatic HBV infection (malaise, an- and 12 coinvestigators reported plications,” reported Chun-Jen Liu, ment. orexia, sclera jaundice, and nausea), having no conflicts of interest. Nine MD, of National Taiwan University The study enrolled 111 coinfect- which resolved after treatment with coinvestigators reported being em- College of Medicine and Hospital, ed patients; about two-thirds were entecavir. ployees and shareholders of Gilead, Taipei, and his associates. Although female, and 16% had compensated A total of 74 patients had quan- and one coinvestigator reporting nearly two-thirds of patients de- cirrhosis. All tested positive for tifiable baseline HBV DNA (at least consulting for Gilead. The senior veloped HBV reactivation, less HBsAg at screening, and all but 20 IU/mL). Three received enteca- author disclosed ties to Roche, Bris- than 5% developed alanine amino- one also tested positive at baseline. vir or tenofovir disoproxil fumarate tol-Myers Squibb, Johnson & John- transferase rises at least twice the Mean baseline HBV DNA levels based on confirmed HBV reactiva- son, Bayer, MSD, and Taiha. upper limit of normal, and only one were 2.1 log10 IU/mL. Patients re- tion with a concomitant ALT rise patient had symptomatic HBV re- ceived 90 mg ledipasvir plus 400 of at least twice the upper limit of [email protected] activation, which entecavir therapy mg sofosbuvir for 12 weeks, and normal. All were asymptomatic. resolved. This study was the first to levels of HCV RNA, HBV DNA, and There were no cases of liver failure SOURCE: Liu C-J et al. Gastroenter- prospectively evaluate the risk of HBsAg were tested at weeks 1, 2, or death. ology. 2017 Nov 21. doi: 10.1053/j.gas- HBV reactivation during HCV treat- 4, 8, 12, posttreatment week 4, and “Regardless of HBV DNA and/or tro.2017.11.011. Ulcerative colitis is disabling over time

BY AMY KARON Frontline Medical News nderstanding the natural history of uncomplicated disease course and that the U ulcerative colitis (UC) is imperative es- first few years of disease are the most ag- etween 70% and 80% of patients with ulcerative pecially in view of emerging therapies that gressive. A good indicator was that the pro- B colitis relapsed within 10 years of diagnosis and could have the potential to alter the natural portion of patients receiving corticosteroids 10%-15% had aggressive disease in a meta-analysis course of disease. Dr. Fumery and his col- decreased over time. The disheartening of 17 population-based cohorts spanning 1935 to leagues are to be congratulated for conduct- news was that the long-term colectomy rates 2016. ing a comprehensive review of have generally remained stable However, “contemporary population-based cohorts different inception cohorts across over time. of patients diagnosed in the biologic era are lacking,” the world and evaluating different The surprising aspect was the [and they] “may inform us of the population-level facets of the disease. They found scarcity of data from North Amer- impact of paradigm shifts in approach to ulcerative that the majority of patients had ica; almost half the studies were colitis management during the last decade, such as a mild-moderate disease course, from Scandinavian countries. early use of disease-modifying biologic therapy and which was most active at the time There was also limited informa- treat-to-target [strategies],” wrote Mathurin Fumery, of diagnosis. Approximately half tion on the impact of biologics MD, of the University of California, San Diego. The the patients require UC-relat- and future research must be un- report was published in the March issue of Clinical ed hospitalization at some time dertaken to evaluate their effect Gastroenterology and Hepatology. during the course of their disease. DR. KHAN on the natural history of disease Population-based observational cohort studies Similarly, 50% of patients received – especially the impact of early follow an entire group in a geographic area over an corticosteroids, and while almost all patients introduction among those who have poor extended time, which better characterizes the true with UC were treated with mesalamine with- prognostic features. This will go a long way natural history of disease outside highly controlled in 1 year of diagnosis, 30%-40% are not on in developing a personalized medicine ap- settings of clinical trials, the reviewers noted. They mesalamine long term. They also identified proach in the management of UC. searched MEDLINE for population-based longitudinal consistent predictors of poor prognosis, studies of adults with newly diagnosed ulcerative including young age at diagnosis, extensive Nabeel Khan, MD, is assistant professor of colitis, whose medical records were reviewed, and disease, early need for corticosteroids, and clinical medicine, University of Pennsylvania, who were followed for at least a year. They identified elevated biochemical markers. Philadelphia, and director of gastroenterol- 60 such studies of 17 cohorts that included 15,316 These results are reassuring because they ogy, Philadelphia Veterans Affairs Medical patients in southern and northern Europe, Australia, reinforce the previous observations that Center. He has received research grants from Israel, the United States, Canada, China, Hong Kong, roughly half the patients with UC have an Takeda, Luitpold, and Pfizer. Continued on following page 10 NEWS MARCH 2018 • GI & HEPATOLOGY NEWS FROM THE AGA JOURNALS No short-term link found between PPIs, MI

BY AMY KARON Insurance plans. The study data Frontline Medical News spanned from 2001 to 2014, and n the late 2000s, several large In this context, the epidemio- patients were followed from their I epidemiologic studies suggest- logic study by Suzanne Landi and tarting a prescription proton initial antacid prescription until ed that proton pump inhibitors her associates provides further pump inhibitor (PPI) con- they either developed a first-ever (PPIs) increase the risk for MI in reassurance that PPIs do not Sferred no short-term increase MI, stopped their medication, or users of clopidogrel. There was cause MI. Two insurance cohorts in risk for myocardial infarction in a left their insurance plan. Median a proposed mechanism: comprising over 5 mil- large retrospective insurance claims follow-up times were 60 days in PPIs competitively inhibit lion patients were used study. patients with commercial insur- cytochrome P450 iso- to compare PPI users Over a median follow-up of 2-3 ance and 96 days in patients with enzymes, which blocked with histamine2-recep- months, estimated weighted risks Medicare Supplemental Insurance, clopidogrel activation tor antagonist users of first-ever MI were low and sim- which employers provide for indi- and, ex vivo, increased after adjusting for base- viduals who are at platelet aggregation. It line differences between least 65 years old. sounded scary – but for- the two groups. The After controlling tunately, some reassuring large size of the dataset for numerous mea- data quickly emerged. In allowed the authors to surable clinical and 2007, the COGENT trial DR. FREEDBERG make precise estimates; ilar regardless of whether patients demographic confounders, the randomized patients we can say with confi- started PPIs or histamine2-recep- estimated 12-month risk of MI with cardiovascular disease to a dence that there was no clinically tor antagonists (H2RAs), reported was about 2 cases per 1,000 com- PPI/clopidogrel versus a placebo/ relevant PPI/MI risk in these Suzanne N. Landi of the University mercially insured patients and clopidogrel combination pill. After data. of North Carolina at Chapel Hill, about 8 cases per 1,000 Medicare 3 years of follow-up, there was Can we forget about PPIs and and her associates. “Contrary to Supplemental Insurance enrollees. no difference in rates of death or MI? These days, my patients wor- prior literature, our analyses do The estimated 12-month risk of cardiovascular events. In the glar- ry more about dementia or chron- not indicate increased risk of MI in MI did not significantly differ be- ing light of this randomized con- ic kidney disease. But the PPI/ PPI initiators compared to hista- tween users of PPIs and H2RAs, trolled trial data, earlier studies MI story is worth remembering. mine2-receptor antagonist initia- regardless of whether they were didn’t look so convincing. Large epidemiologic studies are tors,” they wrote in the March issue enrolled in commercial insurance So why won’t the PPI/MI issue sometimes contradicted by sub- of Gastroenterology. plans (weighted risk difference die? In part because COGENT was sequent studies and need to be Epidemiologic studies have pro- per 1,000 users, –0.08; 95% con- a relatively small study. It includ- evaluated in context. duced mixed findings on PPI use fidence interval, –0.51 to 0.36) or ed 3,761 patients, but the main and MI risk. Animal models and ex Medicare Supplemental Insurance result depended on 109 cardio- Daniel E. Freedberg, MD, MS, is an vivo studies of human tissue indi- (weighted risk difference per 1,000 vascular events. Naysayers have assistant professor of medicine at cate that PPIs might harm coronary users, –0.45; 95% CI, –1.53 to argued that perhaps if COGENT the Columbia University Medical vessels by increasing plasma levels 0.58) plans. had been a bigger study, the result Center, New York. He has consulted of asymmetrical dimethylarginine, Each antacid class also conferred would have been different. for Pfizer. which counteracts the vasoprotec- a similar estimated risk of MI at tive activity of endothelial nitrous 36 months, with weighted risk dif- oxide synthase, the investigators ferences of 0.44 (95% CI, –0.90 to among commercial insurance plan because of concerns related to MI noted. 1.63) per 1,000 commercial plan members. risk.” To further assess PPIs and risk of enrollees and –0.33 (95% CI, –4.40 “Previous studies have examined The researchers received no grant MI while minimizing potential con- to 3.46) per 1,000 Medicare Sup- the risk of MI in PPI users and com- support for this study. Ms. Landi founding, they studied new users of plemental Insurance plan enrollees, pared directly to nonusers, which disclosed a student fellowship from either prescription PPIs or an active the researchers reported. Weighted may have resulted in stronger con- UCB Biosciences. comparator, prescription H2RAs. estimated risk ratios also were sim- founding by indication and other The dataset included administrative ilar between drug classes, ranging risk factors, such as BMI [body [email protected] claims for more than 5 million pa- from 0.87 (95% CI, 0.76 to 0.99) at mass index] and baseline cardio- tients with no MI history who were 3 months among Medicare Supple- vascular disease,” the investigators SOURCE: Landi SN et al. Gastroenter- enrolled in commercial insurance mental Insurance enrollees to 1.08 wrote. “Physicians and patients ology. 2017 Nov 6. doi: 10.1053/j.gas- plans or Medicare Supplemental (95% CI, 0.87 to 1.35) at 36 months should not avoid starting a PPI tro.2017.10.042.

Continued from previous page up to 15% of patients with ulcerative colitis un- disease course, or whether the natural history derwent colectomy within 10 years, a risk that of this disease differs in newly industrialized Indonesia, Macau, Malaysia, Singapore, Sri Lan- mucosal healing helped mitigate. Use of corti- nations or the Asia-Oceania region, they add- ka, and Thailand. costeroids dropped over time as the prevalence ed. Left-sided colitis was most common (medi- of immunomodulators and anti–tumor necrosis Dr. Fumery disclosed support from the an, 40%; interquartile range, 33%-45%) and factor therapy rose. French Society of Gastroenterology, AbbVie, about 10%-30% of patients had disease exten- “Although ulcerative colitis is not associated MSD, Takeda, and Ferring. Coinvestigators sion. Patients tended to have mild to moderate with an increased risk of mortality, it is associ- disclosed ties to numerous pharmaceutical disease that was most active at diagnosis and ated with high morbidity and work disability, companies. subsequently alternated between remission and comparable to Crohn’s disease,” the reviewers mild activity. However, nearly half of patients concluded. Not only are contemporary popula- [email protected] were hospitalized at some point because of ul- tion-level data lacking, but it also remains un- cerative colitis, and about half of that subgroup clear whether treating patients with ulcerative SOURCE: Fumery M et al. Clin Gastroenterol Hepatol. was rehospitalized within 5 years. Furthermore, colitis according to baseline risk affects the 2017 Jun 16. doi: 10.1016/j.cgh.2017.06.016. Be the one who sees it all The enhanced visual breadth, sharper image clarity, and exceptional responsiveness of the EVIS EXERA III platform puts you in control of every endoscopy procedure. With industry-leading technology and trusted support, Olympus helps you maximize what you can achieve in endoscopy.

Contact your Olympus Sales Representative or call 800-848-9024. ©2018 Olympus America Inc. Registered Trademark of Olympus or its affiliates. I www.medical.olympusamerica.com I OAIGI0118AD24647

GIHEP_11.indd 1 2/15/2018 9:59:10 AM 12 NEWS FROM THE AGA MARCH 2018 • GI & HEPATOLOGY NEWS AGA’s FMT National Registry enrolls first patient

he AGA Fecal Microbiota Trans- ology Center of Connecticut/Medical will follow up with the patient four a program of the AGA Center for plantation (FMT) National Research Center of Connecticut by times over the next 2 years and Gut Microbiome Research and Ed- T Registry is officially underway! Paul Feuerstadt, MD. The patient be- report back on the patient’s health ucation, was established in August The first patient enrolled in the FMT ing treated had experienced multiple post-FMT. The patient will also pro- 2016 after receiving funding from National Registry received a fecal recurrences of C. difficile infection. vide yearly reports for up to 10 years. the National Institute of Allergy and transplant through the Gastroenter- As part of the registry, Dr. Feuerstadt The AGA FMT National Registry, Infectious Diseases (NIAID) of the NIH (award number R24AI118629). The registry aims to enroll 75 sites and track 4,000 patients for 5-10 years after their FMT procedure. The data collected from this registry When you have to be right will guide physicians in determining when to use FMT on their patients and will provide much-needed infor- mation on the potential risks associ- ated with stool transplants. If you’re interested in participat- ing in the registry, email FMTRegis- [email protected].

As part of the registry, Dr. Feuerstadt will follow up with the patient four times over the next 2 years and report UpToDate®— access back on the patient’s health. New registry collaborators current, comprehensive AGA will collaborate with the Amer- ican Gut Project – an academic clinical content you effort run by the laboratory of Rob Knight, PhD, professor and director (and your patients) of the Center for Microbiome Inno- vation at the University of Califor- can rely on nia, San Diego – to build a biobank of stool samples from participants in the FMT National Registry. Amer- With UpToDate, you can easily access ican Gut will receive stool samples more than 10,500 evidence-based, from registry participants before and after their FMT. The microbiota practice-oriented topics covering 24 will be sequenced in each sample, and remaining material will be fro- specialties, making it one of the most zen to be made available for future comprehensive medical resources research. Eventually, this informa- tion could help doctors screen and available. Try the resource select the best donor samples for individual patients. More than 6,300 expert physician authors AGA will also collaborate with 99% of subscribers OpenBiome, a public stool bank and draw from the latest evidence presented nonprofit research organization that provides clinicians with rigor- in more than 460 medical journals, online would recommend ously screened, ready-to-use stool medical resources and reports by major preparations for fecal transplant procedures. As the only public stool national and international agencies to to a colleague!* bank in the country, OpenBiome provide information you can trust. serves as the source of stool prepa- rations for nearly 1,000 clinical partners performing FMT across the U.S. For patients enrolled in the Visit go.uptodate.com/agautd to learn more. registry who receive OpenBiome FMT material, OpenBiome will provide screening information and *UpToDate Individual Subscriber Survey, October 2014 (N=15,992) samples to support the registry’s research analyses. Learn more at www.gastro.org/FMTRegistry.

[email protected] GIHEPNEWS.COM • MARCH 2018 NEWS FROM THE AGA 13 DDW® 2018 Headlines from the 2018 general Gastrointestinal Cancers registration is Symposium

he 2018 Gastrointestinal Cancers Sympo- profile, thus positioning cabozantinib for po- now open T sium took place Jan. 18-20, 2018, in San tential approval in the second-line setting in Francisco. During the meeting, investigators HCC. eneral registration and housing for presented groundbreaking research designed RAINFALL Meets Primary Endpoint, But Digestive Disease Week® (DDW) 2018 to improve the diagnosis and treatment of Ramucirumab Will Not Be Pursued for a G are now open. Registering during the gastrointestinal cancers. Here are some of the First-Line Indication in G-GEJ Cancer early-bird period (until April 18) guarantees most noteworthy headlines from the 2018 Results of the global, randomized, dou- a savings of at least $80 on your registration. meeting. ble-blind, placebo-controlled, phase III RAIN- Why DDW? Promising Results Using Liquid Biopsy FALL trial established the statistical benefit Just as monumental as this year’s host city, to Improve CRC Early Detection of ramucirumab, a monoclonal antibody Washington, D.C., DDW is the premier meet- Researchers in Taiwan developed a screen- targeting VEGFR-2, added to standard chemo- ing for GI professionals. Come to DDW 2018, ing test for early colorectal cancer (CRC) de- therapy for patients with previously untreated taking place June 2-5, to: tection that requires a simple blood draw to metastatic gastric or gastroesophageal junc- • Choose from an extensive program of assess for circulating tumor cells in the blood. tion (G-GEJ) adenocarcinoma. The findings high-quality education presented in a vari- The test demonstrates 88% accuracy to detect revealed a significant 25% reduction in the ety of learning formats. all stages of colorectal illness, including pre- risk of disease progression or death for the • Explore research unveiled in more than cancerous lesions. If validated and made com- primary endpoint of progression-free survival 4,000 poster presentations and over 1,000 mercially available, this test could be readily (PFS). However, the reduction corresponded abstract presentations. integrated into a patient’s routine physical to only a 9-day improvement in median PFS, • Network and share capital ideas with more exam, thereby increasing CRC screening com- so the clinical benefit of frontline ramucirum- than 14,000 other attendees from around pliance. ab is debatable. the world. CELESTIAL Results May Lead to Cabozantinib The Gastrointestinal Cancers Symposium is • Browse an extensive Exhibit Hall featuring Approval in Second-Line HCC cosponsored by AGA, the American Society of the latest products and services in gastro- The phase III CELESTIAL trial met its pri- Clinical Oncology (ASCO), the American Soci- enterology and related fields. mary endpoint by demonstrating a survival ety for Radiation Oncology (ASTRO) and the Whether your area of expertise is in pa- advantage with cabozantinib in patients with Society of Surgical Oncology (SSO). tient care, research, education, or adminis- advanced hepatocellular carcinoma (HCC) that More news from the 2018 Gastrointestinal tration, DDW has something for you. Register progressed following prior systemic therapy. Cancers Symposium is available at gicasym. today at ddw.org to secure your spot. Other outcomes included improvements in org/daily-news. progression-free survival and objective re- [email protected] sponse rate, as well as an acceptable safety [email protected] Thank you to our top Community contributors

017 was a busy year in the AGA part of their regular routines in this Kedrin: “I find the case discus- figure out the best therapeutic 2 Community, our member-on- brief Q&A. sions informative. I learn a great approach.” ly discussion forum. Some of our Thanks for being such an active deal about current trends and opin- Was there a conversation in the AGA favorite discussions included chal- member of the AGA Community! Why ions on important topics in the GI Community in 2017 that was your fa- lenging clinical cases you shared, do you contribute? world.” vorite? remembering your colleague Dr. Dr. Kane: “You are welcome! I What do you like to do in your free Kane: “All conversations have Marv Sleisenger and first-hand contribute because I feel I have time? merit, none stick out as a favorite.” recaps of AGA’s Advocacy Day expe- helpful suggestions and recom- Kane: “I enjoy cooking and Kedrin: “Oh, there are several. I riences. mendations for managing difficult binge-watching Netflix.” recall a patient case where there Thank you to everyone who con- patient scenarios as well as for pro- Kedrin: “I bake bread and run a were several thought leaders tributed to the conversations in fessional issues.” gastroenterology literature review in the field who had a disagree- 2017, making the AGA Community Dr. Kedrin: “I think it is important podcast called ‘GI Pearls.’” ment about the best approach to a hub for collaboration to ever-ex- for GI docs to be a part of a larger What’s your approach to handling treatment. The work-life balance pand the field of GI. community, stay informed on latest a difficult patient case you come conversation [Early Career Group Tied for the title of top contrib- guidelines, research publications across in your practice? members only] was also very good. utor in 2017 were Dmitriy Kedrin, and approaches to difficult cases, Kane: “I reach out to as many of I also enjoyed reading about differ- MD, PhD, of Elliot Hospital in Man- where more than one road can be my colleagues as I think appropri- ent opinions regarding the values chester, N.H., and Sunanda Kane, taken. I feel that it is a great forum ate who may have some experience of randomized versus observa- MD, MSPH, AGAF, of Mayo Clinic in for someone like me, relatively ju- or thoughts about how to help a tional trials that happened a while Rochester, MN. nior gastroenterologist.” difficult patient.” back.” Both are key influencers in the Why do you enjoy being part of the Kedrin: “I often seek advice of View the top discussions and forum, especially with helping col- AGA Community? other clinicians, some with more contributors from 2017 on the AGA leagues manage challenging patient Kane: “I feel engaged with my col- expertise in a particular area. I Community homepage, for a limited cases. Learn more about each con- leagues who I otherwise do not see also go to the literature and try time. tributor and why keeping up with on a regular basis, and get to ‘meet’ to learn more that way, help ex- the Community is an important new ones.” pand my differential as well as [email protected] 14 NEWS FROM THE AGA MARCH 2018 • GI & HEPATOLOGY NEWS AGA Pres. Sheila Crowe spends the day on Capitol Hill GA President Sheila Crowe, Removing Barriers to Colorectal With the emergence of new biologics many of the offices that we met with MD, FRCPC, FACP, FACG, AGAF, Cancer Screening Act to treat diseases like inflammatory will support HR 2077. Read more A recently spent the day on Fixing the current coinsurance prob- bowel disease, more and more di- about the issue. Capitol Hill meeting with lawmakers lem for Medicare beneficiaries who gestive disease patients are being to advocate for AGA legislative pri- undergo a screening colonoscopy subject to these protocols, which can Food is Medicine Working Group orities including increasing funding that becomes therapeutic remains Dr. Crowe also had a productive for NIH and biomedical research, a top AGA priority. Most of the of- meeting with Rep. Jim McGovern’s, support for the Removing Barriers fices that Dr. Crowe met with were D-MA, office and learned more about to Colorectal Cancer Screening Act, cosponsors of the legislation, the Re- the recently created Food is Medicine and support for the Restoring the moving Barriers to Colorectal Cancer Working Group that he has initiated. Patient’s Voice Act. Dr. Crowe met Screening Act (HR 1017/S.479), that McGovern is the Ranking Member with eight congressional offices and would waive coinsurance payment of the Agriculture Committee’s Sub- received helpful feedback on the up- regardless of the screening outcome. committee on Nutrition which is coming agenda in Congress and how Dr. Crowe shared her experience responsible for our nation’s nutrition it impacts AGA’s priorities. with patients and the financial bur- guidelines and the Supplemental den this places on beneficiaries who Nutrition Assistance Program. The NIH funding need to be screened. Rep. Raul Ruiz, Working Group will focus on costs Dr. Crowe stressed the need for D-CA, and Rep. Scott Peters, D-CA, related to hunger and the importance increased funding for NIH and bio- both members of the House Energy of nutrition in treating chronic illness medical research, making the case and Commerce Committee and sup- Dr. Sheila Crowe lobbied for AGA and disease. AGA looks forward to that funding NIH not only improves porters of the bill, will continue to priorities on Capitol Hill. working with McGovern and mem- the quality of life for Americans, advocate that the bill receive a hear- bers of the Working Group on this but also contributes to our nation’s ing this year to help move it through have adverse effects on their health. bipartisan initiative. economic competitiveness. Fortu- Congress. The bill continues to have Restoring the Patient’s Voice Act (HR nately, the offices that we met with wide bipartisan support. Read more 2077) would provide patients and Capitol Hill needs to were very supportive of increasing about the issue and how you can ex- providers with a fair and equitable hear the voice of GI NIH funding, including the offices of plain it to your patients. appeals process when step therapy In conjunction with Dr. Crowe’s House and Senate Appropriations has been imposed and provides com- visit, AGA launched a Virtual Advo- Subcommittee Chairs Tom Cole, Step therapy mon sense exceptions for the provid- cacy Day to encourage members to R-OK, and Roy Blunt, R-MO, who More and more patients are being er to appeal. Dr. Crowe spoke of the contact their legislators in support have worked in a bicameral fashion subject to step therapy protocols, also impact this policy is having on diges- of the issues that Dr. Crowe was to increase funding for NIH. Both of- known as “fail first” under which they tive disease patients and the burden advocating during her meetings. We fices were confident that leadership are required to try and fail some- it puts on physician practices that thank those members who took time was close to a deal to increase the times two or three therapies before have to take time away from patients out of their schedules to take action. current budget caps, which would receiving coverage of the initial ther- to navigate the convoluted insurance enable increased funding for NIH. apy recommended by their physician. appeals process. We are hopeful that [email protected] Legacy Society members sustain research The makings of a grand celebration GA Legacy Society members share a desire The AGA Research Foundation’s mission is A to guarantee long-term support for diges- to raise funds to support young researchers in eginning with a memorable gathering at tive disease research. Through their foresight gastroenterology and hepatology. Gifts to the B the United States Library of Congress in and generosity, they help ensure the continued foundation support researchers who are work- 2007, the AGA Benefactors’ Dinner has wel- momentum of discovery that has characterized ing to advance our understanding of digestive comed members of the AGA Legacy Society GI medicine in recent decades. Legacy Society diseases. and other AGA dignitaries to special locations member donations directly support young GI “I am extremely grateful to be selected for this nationwide. The Folger Shakespeare Library investigators as they establish independent re- award. I would like to thank the foundation donors will be the location of the 2018 AGA Research search careers. for their generous support. This award will me Foundation Benefactors’ Dinner during DDW Legacy Society members are the most generous build a research program to better understand in Washington, DC. Just steps from the Capitol, individual donors to the AGA Research Founda- mechanisms that promote growth of cholangiocar- the Great Hall and Pastor Reading room are a tion. Members of the AGA Legacy Society provide cinoma,” remarks Silvia Affo, PhD, Columbia Uni- spectacular setting for an enjoyable evening tax-deductible gifts to the AGA Research Foun- versity, 2017 AGA Research Scholar recipient. with friends. dation of $5,000 or more per year for 5 years Donors who make gifts at the Legacy Society ($25,000 total) or $50,000 or more in a planned level before DDW will receive an invitation to the gift, such as a bequest. All Legacy Society contri- annual Benefactors’ Dinner at the Folger Shake- butions go directly to support research awards. speare Library in Washington, DC. Individuals ibrary AGA members support young researchers at a interested in learning more about Legacy Society l critical decision point in their lives – when many membership may contact Stacey Hinton Tuneski, consider giving up their research careers due to a Senior Director of Development at stuneski@ hakespeare

lack of funding. “I am honored to be a recipient of gastro.org or via phone (301) 222-4005. More s the Research Scholar Award. I would like to thank information on the AGA Legacy Society including olger

the foundation for their generous contribution the current roster and acceptance form is available f that will fund a crucial transition in my career,” on the foundation’s website at www.gastro.org/ of said Jose Saenz, MD, PhD, Washington University legacysociety.

School of Medicine and 2017 AGA – Gastric Cancer courtesy Foundation Research Scholar Award recipient. [email protected] Folger Shakespeare Library, Washington, DC GIHEP_15.indd 1 1/19/2018 10:23:53 AM 22 IBD AND INTESTINAL DISORDERS MARCH 2018 • GI & HEPATOLOGY NEWS

nificant differences in endoscopic for both comparisons with placebo; Multiple targets for new drugs remission among patients on the N Engl J Med. 2017;376:1723-36). Pipeline from page 1 study drug, compared with those on “In subgroup analyses, it looks like placebo (17% vs. 3%; P = .0015) as the 10-mg dose is more effective for ous etrolizumab (100 mg at weeks 0, treatment with intravenous usteki- well as endoscopic response (32% maintenance in patients who previ- 4, and 8, with placebo at week 2 or a numab. The estimated primary vs. 13%; P = .0104). The trial pro- ously received anti-TNF therapy,” said 420-mg loading dose at week 0 fol- completion date is April 12, 2018. vides further evidence that selective Dr. Sandborn, who also directs the lowed by 300 mg at weeks 2, 4, and Meanwhile, a phase 2a trial of 119 blockade of interleukin 23 via inhi- UCSD IBD Center. “All secondary out- 8), or matching placebo (The Lancet patients with moderate to severe bition of p19 might be a viable ther- comes were positive. You don’t see 2014 348;309-18). They found that Crohn’s disease who had failed apeutic approach in Crohn’s disease. that very often. It tells you that this is etrolizumab was more likely to lead treatment with tumor necrosis fac- a really effective therapy. It’s current- to clinical remission at week 10 tor (TNF) antagonists showed that ly being reviewed by the FDA.” than was placebo, especially at the treatment with MEDI2070 was as- Meanwhile, a phase 2 trial found 100-mg dose. Meanwhile, a more sociated with clinical improvement that a higher percentage of patients recent study of the anti-MadCAM after 8 and 24 weeks of therapy with mild to moderate Crohn’s dis- antibody PF-00547659 in patients (Gastroenterol 2017;153:77-86). ease who received a 200-mg dose with moderate to severe ulcerative The investigators also found that of filgotinib over 10 weeks achieved colitis found that it was better than patients with baseline serum IL-22 clinical remission, compared with placebo for induction of remission concentrations above the median those who received placebo (47% (The Lancet 2017;390:135-44). In- threshold concentration of 15.6 pg/ vs. 23%, respectively; P = .0077; vestigators for the trial, known as mL treated with MEDI2070 had The Lancet 2017;389:266-75). Se- TURANDOT, found that the greatest higher rates of clinical response and rious treatment-emergent adverse clinical effects were observed with remission, compared with those effects occurred in 9% of the 152 the 22.5-mg and 75-mg doses. “This with baseline concentrations below patients treated with filgotinib and is now being taken forward in phase this threshold. According to Dr. Dr. William J. Sandborn 3 of the 67 patients treated with 3 trials by Shire,” Dr. Sandborn said. Sandborn, who was not involved in placebo. According to Dr. Sandborn, The anti-interleukin 12/23 anti- the study, these results provide sup- Janus kinase (JAK) inhibitors un- filgotinib is currently in phase 3 body (p40) ustekinumab is being port for further research on the val- der investigation for Crohn’s disease development trials for both Crohn’s investigated for efficacy in UC, ue of IL-22 serum concentrations to include tofacitinib, filgotinib, upadaci- disease and UC. At the same time, while anti-interleukin 23 (p19) predict response to MEDI2070. “It’s tinib, baricitinib, and TD-1473. In the results from an unpublished study antibodies being studied include a small study and is hypothesis gen- OCTAVE Induction 1 trial led by Dr. presented at the annual Digestive brazikumab (MEDI2070), risanki- erating,” he said. “This will need to Sandborn, 18.5% of the patients in Disease Week in 2017 found that 16 zumab (BI-655066), geslekumab, be confirmed in subsequent trials.” the tofacitinib group achieved remis- weeks of treatment with the inves- mirikizumab (LY3074828), and In a short-term study of 121 pa- sion at 8 weeks, compared with 8.2% tigational agent upadacitinib led to tildrakizumab (MK-3222). In 2015, tients with active Crohn’s disease, in the placebo group (P = .007); in the modified clinical remission in 37% Janssen launched NCT02407236, Brian G. Feagan, MD, Dr. Sandborn, OCTAVE Induction 2 trial, remission of patients on the 24-mg bid dose, with the aim of evaluating the ef- and associates found that risanki- occurred in 16.6% vs. 3.6% (P less compared with 30% of patients in fectiveness and safety of continuing zumab was more effective than than .001). In the OCTAVE Sustain the 6-mg bid dose. There was also ustekinumab as a subcutaneous (in- placebo for inducing clinical remis- trial, remission at 52 weeks occurred a dose response for endoscopic re- jection) maintenance therapy in pa- sion, particularly at the 600-mg in 34.3% of the patients in the 5-mg sponse. “Based on these data, this tients with moderately to severely dose, compared with the 200-mg tofacitinib group and 40.6% in the drug is now in a phase 3 trial, so active UC who have demonstrated dose (Lancet 2017;389:1699-709). 10-mg tofacitinib group vs. 11.1% in lots of JAK inhibitors are coming a clinical response to an induction The researchers also observed sig- the placebo group (P less than 0.001 along,” he said. Sphingosine-1–phosphate recep- tor 1 (S1P1) modulators currently under investigation include fingoli- mod (not studied in IBD), ozanimod, and etrasimod. “These modulators cause the S1P1 receptors that are expressed on the surface of positive lymphocytes to be eluded back into the cell, which leads to a reversible reduction in circulating lympho- cytes in the blood,” Dr. Sandborn 2018 explained. In a phase 2 trial, he and his associates found that UC patients AGA who received ozanimod at a daily dose of 1 mg had a slightly higher rate of clinical remission, compared with those who received placebo, but the study was not sufficiently Saturday, June 2, 2018 powered to establish clinical effi- 8:15 a.m.–5:30 p.m. cacy or assess safety (N Engl J. Med 2016;374:1754-62). FROM ABSTRACT TOSunday, REALITY June 3, 2018 Dr. Sandborn reported having 8:30 a.m.–12:35 p.m. consulting relationships with Take- da, Genentech, Pfizer, Shire, Amgen, Learn more at pgcourse.gastro.org. and many other pharmaceutical POSTGRADUATE RegisterCOURSE by April 18, 2018, and save $75. companies. 2200-080EDU_17-16 [email protected] GIHEPNEWS.COM • MARCH 2018 IBD AND INTESTINAL DISORDERS 23 Delayed ileal pouch AA had less postop events

BY DOUG BRUNK ectomy (group A), and 819 had de- P less than .01). tion and operator factors. Also, data Frontline Medical News layed pouch creation (group B). After controlling for confounders, were not collected for the purposes Compared with patients in group patients in group B were significant- of studying inflammatory bowel LAS VEGAS – Delayed creation of B, those in group A were older (a ly less likely to have major compli- disease. an ileal pouch anal anastomosis in median age of 40 years vs. 37 years, cations (relative risk, 0.72), minor “This is the first prospective as- patients with ulcerative colitis (UC) respectively; P less than .01), were complications (RR, 0.48), unplanned sessment of morbidity following was associated with a lower risk of more likely to be on an immuno- readmissions (RR, 0.95), and un- IPAA creation in UC patients from a postoperative events, compared with suppressant (51% vs. 15%; P less planned reoperations (RR, 0.42). national database,” Dr. Kochar con- creating the pouch at the time of ini- than .01), have a lower median pre- In the subgroup analysis, Dr. Ko- cluded. “Delayed pouch procedures tial surgery, results from an analysis operative albumin level (3.9 vs. 4.2; char and her associates observed are associated with a lower risk of of national data demonstrated. P less than .01), and a longer medi- that patients who underwent TAC unplanned reoperations and major “More than 600,000 Americans an length of stay (6 days vs. 5 days; were significantly older, compared and minor complications. Immuno- have UC, and 20%-30% of them re- P less than .01). with patients in group A (a median suppression at the time of pouch quire surgical management,” Bhara- On unadjusted analyses, the re- of 46 years vs. 40 years, respective- creation may result in an increased ti Kochar, MD, said at the annual searchers also observed that, at 30 ly; P less than .01), and a higher risk of adverse events postopera- congress of the Crohn’s & Colitis days, patients in group A had signifi- proportion were on immunosup- tively. The findings can be valuable Foundation, a partnership of the cantly more major complications, pressants (69% vs. 51%; P less than for preoperative risk assessment Crohn’s & Colitis Foundation and such as mortality and cardiac arrest .01). “Despite these factors, the risk and postoperative management.” the American Gastroenterological (12.4% vs. 8.7%; P less than .01); mi- of adverse events after TAC was Dr. Kochar reported having no Association. “The surgical proce- nor complications, such as superficial lower,” Dr. Kochar said. financial disclosures. dure of choice for many UC patients surgical site infections and pneumo- She acknowledged certain lim- is total proctocolectomy with ileal nia (11.8% vs. 6.1%; P less than .01); itations of the study, including the [email protected] pouch anal anastomosis creation.” unplanned readmissions (statistically inability to accurately determine According to Dr. Kochar, an ad- similar at 23.3% vs. 21.3%); and un- the risk of linked surgeries together SOURCE: Kochar B et al. Crohn’s & Coli- vanced fellow in inflammatory planned reoperations (7.7% vs. 3.8%; and the inability to assess institu- tis Congress 2018 Clinical Abstract 11. bowel diseases at the University of North Carolina at Chapel Hill, ex- isting American medical literature regarding ileal pouch anal anasto- Higher BMI linked to problems in IBD patients mosis (IPAA) comes mostly from quaternary care centers and com- pares one-stage procedures with BY DOUG BRUNK or hospitalization, a single-cen- Gastroenterological Association. multistage procedures. Frontline Medical News ter, retrospective cohort study “Today, 15%-40% of IBD patients “The risks between two- to three- demonstrated. are obese. This is significant stage procedures are not described, LAS VEGAS – Higher body mass “The problem of IBD and obesi- because there is a decreased and there are no prospective na- index among inflammatory ty is on the rise,” Soumya Kurnool prevalence of remission and an tional reports of postoperative bowel disease (IBD) patients is said at the annual congress of the increased risk of relapse in obese adverse events after IPAA creation,” independently associated with Crohn’s & Colitis Foundation, a IBD patients. These patients also she said. an increased risk of treatment partnership of the Crohn’s & Coli- have a higher annual burden of Using data from the National failure and IBD-related surgery tis Foundation and the American Continued on following page Surgical Quality Improvement Pro- gram, Dr. Kochar and her associates conducted an observational cohort analysis of 2,390 adult patients with a postoperative diagnosis of UC who underwent IPAA proce- 2018 AGA dures between 2011 and 2015. Their aims were to evaluate adverse TECH SUMMIT events within 30 days after an IPAA creation and to compare adverse Connecting Stakeholders events between pouch creation at in GI Innovation the time of colectomy and delayed pouch creation. MARCH 21-23, 2018 | BOSTON, MA They also performed a subanal- Explore critical elements impacting the adoption, ysis of total abdominal colectomy coverage and reimbursement for new GI with ileostomy (TAC), the first stage technologies in today’s health care environment. in the delayed pouch procedures, You’ll be able to network and engage with leaders versus pouch creation at the time of from the physician innovator, medtech, investor colectomy. Multivariable modified and regulatory communities to help shape Poisson regression models were future directions and decisions. used to estimate risk ratios adjust- ed for age, sex, race, body mass REGISTER TODAY AT index, smoking status, diabetes, preoperative albumin, and Amer- techsummit.gastro.org ican Society of Anesthesiologists class. Developed in collaboration with SAGES. Of the 2,390 patients, 1,571 had 2691-014MIT_17-6 pouches created at the time of col- 24 IBD AND INTESTINAL DISORDERS MARCH 2018 • GI & HEPATOLOGY NEWS FDA issues safety alert for loperamide

BY LORI LAUBACH effort to increase absorption and effects related to the use of these tion loperamide and to the Drug Frontline Medical News penetration across the blood- products to the FDA’s MedWatch Facts label of OTC loperamide prod- brain barrier, enhancing the Safety Information and Adverse ucts. The FDA is working to evaluate he Food and Drug Adminis- euphoric effects of loperamide. Event Reporting Program. this safety issue and will update the tration announced Jan. 30 Additionally, some individuals are In 2016, the FDA issued a Drug public when more information is T that it has issued a Med- using high doses of loperamide Safety Communication and added available. Watch safety alert on to mitigate against the warnings about serious heart prob- the use of the over-the- symptoms of opioid with- lems to the drug label of prescrip- [email protected] counter (OTC) antidiar- drawal, according to the rhea drug, loperamide. FDA. Currently, the FDA is Loperamide is approved Continued from previous page modifications; 15% had IBD-related working with manu- to help control symp- surgery, and 19% had IBD-related facturers to use blister toms of diarrhea. The hospitalization.” hospitalization. packs or other sin- maximum recommended Obesity also is associated with After adjusting for age, sex, gle-dose packaging and to limit daily dose for adults is 8 mg per increased drug clearance for all disease duration, prior hospital- the number of doses in a package. day for OTC use and 16 mg per biologic agents and higher odds of ization, prior anti-TNF therapy, The alert comes after receiving day for prescription use. It acts failing anti-TNF therapy in other steroid use, and albumin level, continuous reports of serious heart on opioid receptors in the gut to immune-mediated inflammatory Ms. Kurnool and her associates problems and deaths with the use slow the movement in the intes- diseases, said Ms. Kurnool, a sec- found that every 1-kg/m2 increase of much higher than recommend- tines and decrease the number of ond-year student at the University in BMI was associated with a 4% ed doses of loperamide, mainly bowel movements. of California, San Diego. “Howev- higher risk of treatment failure among people who are intention- It is noted that much higher er, the research on the impact of (adjusted hazard ratio, 1.04), an ally misusing or abusing the prod- than recommended doses of lop- obesity on treatment response to 8% higher risk of surgery or hos- uct, regardless of the addition of a eramide, either intentionally or biologic agents in IBD is sparse and pitalization (adjusted HR, 1.08), warning to the medicine label and unintentionally, can result in se- conflicting.” and a 6% lower risk of achieving a previous communication. The rious cardiac adverse events, in- She and her associates set out endoscopic remission (adjusted FDA states that loperamide is a cluding QT interval prolongation, to evaluate the effect of obesity on HR, 0.94). safe drug when used as directed. torsade de pointes or other ven- response to biologic therapy in pa- Two particular methods of tricular arrhythmias, syncope, tients with ulcerative colitis (UC). abuse are of concern. In some and cardiac arrest. Health care They conducted a single-center, cases, abusers use other drugs professionals and patients can retrospective cohort study of bio- together with loperamide in an report adverse events or side logic-treated adults with UC who started therapy during 2011-2016. The researchers excluded patients who had undergone a prior colec-

tomy, as well as those who were ews n underweight at the time of starting ical FIND a biologic agent and those who had eD fewer than 6 months of follow-up data. The primary outcome was time

YOUR to treatment failure, defined as a runk /F rontline M composite of IBD-related surgery, oug B

hospitalization, and/or treatment D modification. Secondary outcomes Soumya Kurnool is a second-year student NEEDLE were time to IBD-related surgery at the University of California, San Diego and/or hospitalization and whether School of Medicine. the patient achieved endoscopic remission within 1 year of starting “This increase in the risk of biologic therapy. They conducted treatment failure and IBD-related Trying to find that perfect job or candidate multivariate Cox proportional haz- surgery or hospitalization was ard analyses after adjusting for key consistent across strata of pa- can be a daunting task. confounders. tients treated with infliximab and Use the search tools within GICareerSearch.com to brush aside the Ms. Kurnool reported results fixed-dosing regimens,” she said. fray and quickly find your needle in the haystack. from 160 patients with a median “Based on these findings, physicians age of 36 years. Half were male, and should consider proactive monitor- GICareerSearch com the mean follow-up was 24 months. ing in obese patients treated with The median BMI of the cohort was biologic agents.” 24.3 kg/m2; 26% were overweight Ms. Kurnool reported having and 18% were obese. More than received a National Institutes of half of patients (55%) were on in- Health Short Term Training Grant fliximab with weight-based dosing from the University of California, and 45% were on other fixed-dos- San Diego. ing regimens, including 19% on vedolizumab. In terms of outcomes, [email protected] 68% of patients experienced 2525-500COM_15-2 treatment failure. All who failed SOURCE: Kurnool S et al. Crohn’s & treatment underwent treatment Colitis Congress, Clinical Abstract 24. GIHEPNEWS.COM • MARCH 2018 LIVER DISEASE 25

and for fibrosis.” without type 2 diabetes with biop- Who is going down NASH path? Why lean individuals develop sy-proven NASH. “Pioglitazone has Fibrosis from page 1 NASH is not fully understood, but had the greatest benefit in terms Dr. Cusi said he suspects that the of treatment effect, compared to minuria. If you do nothing and they in which some individuals have problem develops at the mitochon- placebo,” Dr. Cusi said. “It’s a ge- don’t die of cardiovascular disease, very insulin-resistant adipose tis- drial level. Results from an unpub- neric drug; at the VA [Veterans they’re going to have a good chance sue and others less so. I would say lished animal model in which mice Affairs], it costs 8 cents per tablet. of getting fibrosis.” that 1 out of 10 are metabolically were fed a high–trans-fat diet for I think that pioglitazone will be to As part of the large popula- healthy, and we don’t understand 24 weeks showed that the mice NASH what metformin has been to tion-based Rotterdam study of exactly why.” developed steatosis by week 8 and type 2 diabetes. The most common individuals aged 45 years and In a recent cross-sectional anal- NASH by week 24. The mice had side effect is weight gain, typically older, researchers found that liver ysis of 352 healthy individuals, Dr. an increase in the tricarboxylic between 4 and 9 lbs. Risks and stiffness of 8 kPa or more by tran- Cusi and his associates found that acid (TCA) cycle, which is typical benefits should be discussed with sient elastography was present intrahepatic triglyceride (IHTG) of the NASH period, as well as an each patient. It should not be used in 5.6% of the study participants accumulation is strongly associ- increase in ceramides. “Perhaps a for NAFLD without biopsy-proven and was strongly associated with unifying hypothesis would be that NASH.” The guideline goes on to steatosis and diabetes (Hepatol- the development of NASH is linked say that it’s currently premature to ogy. 2016;63:138-47). According The researchers observed to inflammation and to insulin consider GLP-1 (glucagonlike pep- to Dr. Cusi, individuals who have that once IHTG accumulation signaling,” Dr. Cusi said. “Not sur- tide–1) agonists for treating liver steatosis without diabetes face reaches about 6%, skeletal prisingly, it had a number of effects disease in patients with NAFLD a 5%-10% risk of fibrosis, while on the mitochondria, and in this or NASH. Meanwhile, vitamin E at those with steatosis and diabetes muscle insulin resistance, animal model it decreases the TCA.” 800 IU has been shown to improve face a 15%-20% risk. “It’s well hypertriglyceridemia, He noted that the biology of fibro- liver histology in nondiabetic established in a number of studies sis remains unknown in humans. adults with NASH, but the risks that if you have fibrosis, you’re at and low HDL cholesterol “What we have been familiar with is and benefits should be discussed high risk not only of cirrhosis, but become fully established. the high-triglyceride, low-HDL pat- with each patient. Vitamin E is not also of hepatocellular carcinoma,” tern,” he said. “If you look at how recommended for NASH in diabetic he said. “The key thing is not de- that correlates with the amount of patients, NAFLD without a liver tecting fat, which is not really the ated with adipose tissue insulin liver fat, it is basically a threshold biopsy, NASH cirrhosis, or crypto- target. The target is if there’s fibro- resistance, supporting the current effect. Once you have steatosis, you genic cirrhosis. sis or not.” Three ways to assess theory of lipotoxicity as a driver don’t see much worse dyslipidemia, The AASLD practice guideline for fibrosis include MR elastogra- of IHTG accumulation (Hepatolo- which is typical of these patients.” also states that the best evidence phy, transient elastography (which gy. 2017;65[4]:1132-44). The re- Recently published guidance from for using SGLT2 (sodium-glucose is the most commonly used), and searchers observed that once IHTG the American Association for the cotransporter–2) inhibitors in NA- fibrosis marker panels. accumulation reaches about 6%, Study of Liver Diseases on the di- FLD comes from animal studies, Liver fibrosis likely starts with skeletal muscle insulin resistance, agnosis and management of nonal- which report a reduction in steato- adipose tissue dysfunction, said hypertriglyceridemia, and low HDL coholic fatty liver disease (NAFLD) sis with and without weight loss. Dr. Cusi, who authored a review cholesterol become fully estab- suggests that patients require a Clinical studies reporting a reduc- on the pathophysiology of interac- lished. “The next question is, How weight loss of 3%-5% to improve tion in steatosis are limited. There tions between adipose tissue and does this correlate with NASH?” Dr. steatosis, but a loss of 7%-10% to are positive observational studies target organs in obesity and the Cusi said. “Our take is that there is improve most histologic features of with a reduction in alanine amino- resulting clinical implications for a threshold effect. Once you have NASH, including fibrosis (Hepatol- transferase and some studies that the management of nonalcoholic a critical amount of triglycerides ogy. 2018;67[1]:328-57). Exercise have shown a reduction in liver fat. steatohepatitis (Gastroenterology. in your liver, some individuals are alone may prevent or reduce steato- “For me, the best option is to tailor 2012;142[4]:711-25.e6). “When going to activate pathways that are sis, but its ability to improve other treatment to the pathophysiology you have insulin-resistant, sick harmful. NASH is not something aspects of liver histology remains of the disease,” Dr. Cusi said. “You adipose tissue, that leads to the exclusive to individuals who are unknown. Bariatric surgery can be reduce fat by weight loss in some accumulation of fat in the liver,” he obese. Lean people can also develop considered in otherwise eligible way, or you change the biology of said. “Steatosis happens in about NASH. The key feature is insulin obese individuals with NAFLD or fat with a thiazolidinedione.” 70% of patients who are obese and resistance, not metabolic syndrome. NASH. The procedure’s impact on Dr. Cusi reported that he has have type 2 diabetes. The dilemma Once you develop a fatty liver, your fibrosis is unknown. received grant support from the is how to know who is going down chances of NASH are comparable The AASLD practice guideline Burroughs Wellcome Fund, the the path to fibrosis. Even if you get to that of an obese individual. The notes that metformin is not recom- American Diabetes Association, and people who are matched for BMIs paradox is that lean individuals get mended for treating NASH in adult the National Institutes of Health. [body mass indexes] between 30 a fatty liver, but when they get a patients, but pioglitazone improves and 35 kg/m2, there is a spectrum fatty liver, they are at risk for NASH liver histology in patients with and [email protected] FDA adds boxed warning to obeticholic acid label

BY ELI ZIMMERMAN prominent warning, to highlight this information in label can increase the risk for liver decompensa- Frontline Medical News the prescribing information of the drug label,” FDA tion, liver failure, and sometimes death. Routinely officials said in a statement. “FDA is clarifying the monitor all patients for biochemical response, he Food and Drug Administration is requiring current recommendations for screening, dosing, tolerability, and PBC progression, and reevaluate Ta boxed warning on the label for obeticholic monitoring, and managing PBC patients with mod- Child-Pugh classification to determine if dosage acid (Ocaliva) to highlight the correct weekly dos- erate to severe liver disease taking Ocaliva.” adjustment is needed.” ing regimen after incorrect daily dosing caused The warning is an update to a September 2017 To report adverse medication events and side ef- severe liver injury in patients with moderate to MedWatch notice on the increased risk for patients fects to the FDA, access the MedWatch program. severe primary biliary cholangitis (PBC). from excessive dosing of obeticholic acid. “FDA is adding a new Boxed Warning, FDA’s most “Dosing higher than recommended in the drug [email protected] 32 LIVER DISEASE MARCH 2018 • GI & HEPATOLOGY NEWS Obesity affects the ability to diagnose liver fibrosis

BY IAN LACY with NAFLD undergoing liver imaging from AGA Resource Frontline Medical News March 2010 through May 2013, was formed to The AGA Obesity Practice Guide provides a validate the findings of the training cohort. comprehensive, multidisciplinary process to ody mass index accounts for a 43.7% discor- The study revealed that BMI was a significant personalize innovative obesity care for safe dance in fibrosis findings between magnetic predictor of the difference between MRE and TE and effective weight management. Learn resonance elastography (MRE) and transient results and made it difficult to assess the stage of B more at www.gastro.org/obesity. elastography (TE), according to a study from the liver fibrosis (2-4 vs. 0-1). After adjustment for University of California, San Diego. age and sex, BMI accounted for a 5-unit increase “This study showed that the grade of obesity of 1.694 (95% confidence interval, 1.145-2.507; P fibrosis in NAFLD should be considered, and is also a significant predictor of discordancy = .008). As BMI increased, so did the discordance this parameter would help to determine when between MRE and TE because the discordance between MRE and TE (P = .0309). The discor- MRE is not needed in future guidelines,” wrote rate between MRE and TE increases with the dance rate was significantly higher in participants Dr. Caussy and her associates. “Further cost-ef- increase in BMI, wrote Cyrielle Caussy, MD, and with BMIs greater than 35 kg/m2, compared fectiveness studies are necessary to evaluate the her colleagues (Clin Gastrolenterol Hepatol. with participants with BMIs below 35 (63.0% vs. clinical utility of MRE, TE, and/or liver biopsy to 2018 Jan 15. doi: 10.1016/j.cgh.2017.10.037).” 38.0%; P = .022), the investigators reported. develop optimal screening strategies for diag- Dr. Caussy of the University of California, San The study had both strengths and limitations. A nosing NAFLD-associated fibrosis.” Diego, and her colleagues had noted that MRE strength of the study was the use of two cohorts, Dr. Chen, Dr. Yin, and Dr. Ehman have intellectual and TE had discordant findings in obese patients. specifically the validation cohort. The use of the liv- property rights and financial interests in elas- To ascertain under what conditions TE and MRE er biopsy as a reference, which is the standard for tography technology. Dr. Ehman also serves as a produce the same readings, Dr. Caussy and her assessing fibrosis, was also a strength of the study. noncompensated CEO of Resoundant. Dr. Sirlin has associates conducted a cross-sectional study of A limitation was that the study was conducted at served as a consultant to Bayer and GE Healthcare. two cohorts with nonalcoholic fatty liver disease specialized, tertiary care centers using advanced All other authors disclosed no conflicts. (NAFLD) who underwent contemporaneous imaging techniques that may not be available at MRE, TE, and liver biopsy. The training cohort other clinics. Additionally, the cohorts included a [email protected] involved 119 adult patients undergoing NAFLD small number of patients with advanced fibrosis. testing from October 2011 through January 2017. “The integration of the BMI in the screening SOURCE: Caussy C et al. Clin Gastrolenterol Hepatol. The validation cohort, consisting of 75 adults strategy for the noninvasive detection of liver 2018 Jan 15. doi: 10.1016/j.cgh.2017.10.037.

Quick quiz answers Baby boomers are the hepatitis C generation Q1. Correct answer: C evaluation of dyspepsia. Gastroen- terology 2005;129:1756-80. BY RICHARD FRANKI in 2014 – an increase of over 67%. Rationale Frontline Medical News For patients aged 73 years and The initial management of dyspepsia Q2. Correct answer: B older, that rate went from 104.4 depends on symptoms and presence ncreases in hepatitis C–related in 2005 to 117.1 in 2014, which of any “alarm features.” In patients Rationale Iinpatient stays for baby boomers translates to a 12% increase, and without “alarm features” present- The patient has a favorable from 2005 to 2014 far outpaced for patients aged 18-51 years, it ing with symptoms suggestive of anatomy for a surgical drainage those of older adults, while young- dropped 15%, from 182.5 to 155.4, hepatobiliary or pancreatic causes, procedure such as a lateral pancre- er adults saw their admissions the AHRQ said in a statistical brief. the initial diagnostic tests should aticojejunostomy (Peustow proce- drop over that period, according Along with the increased hospi- include liver/pancreatic blood tests dure). Surgery has been noted to to the Agency for Healthcare Re- talizations, “acute hepatitis C cases and abdominal imaging. For other provide superior pain relief over search and Quality. nearly tripled from 2010 through dyspeptic patients without alarm 5 years compared with endoscopy. For adults aged 52-72 years, the 2015,” the report noted, which features, initial management would Hospital costs and length of stay rate of inpatient stays involving was “likely the result of increasing include H. pylori testing (breath, stool were similar between the groups. hepatitis C with or without hepati- injection drug use due to the grow- antigen, or antibody) and/or empiric Continued medical therapy is un- tis B, HIV, or alcoholic liver disease ing opioid epidemic.” antisecretory (PPI) therapy. However, likely to add further benefit on top rose from 300.7 per 100,000 popu- for patients who present with “alarm of what she has already achieved. lation in 2005 to 503.1 per 100,000 [email protected] features” such as dysphagia, anemia, EUS-guided celiac plexus block will GI bleeding, anorexia, significant only provide temporary pain relief. Inpatient stays involving hepatitis C by age group weight loss, etc., an upper endoscopy There are limited long-term data 500 should be performed to evaluate for on the effectiveness of total pan- 52-72 years the presence of any upper GI tract createctomy with islet autotrans- 400 malignancy. In this patient, the pres- plantation in alleviating pain. ence of microcytic anemia is an alarm feature. Tricyclic antidepressants References 300 such as amitriptyline may be used as 1. Cahen D.L., Gouma D.J., Laramée 18-51 years ews

treatment for functional dyspepsia, P., et al. Gastroenterology. 200 n after organic causes have been ruled 2011;141(5):1690-5.

out. 2. Conwell D.L., Lee L.S., Yadav D., et edical 100 al. American pancreatic association Rate per 100,000 population ≥73 years Reference practice guidelines in chronic pancre- rontline M 1. Talley N.J., Vakil N.B., Moayyedi atitis. Pancreas. 2014;43:1143-62. 0 F P. American Gastroenterological 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Association technical review on the [email protected] Note: Based on data from the National Inpatient Sample. Source: Agency for Healthcare Research and Quality GIHEPNEWS.COM • MARCH 2018 PANCREAS AND BILIARY TRACT 33 CLINICAL CHALLENGES AND IMAGES

What is your diagnosis? phagia, a percutaneous endoscopic C-reactive protein, 13.5 mg/dL. He gastrostomy tube was placed un- was diagnosed with septic shock and By Uichiro Fuchizaki, MD, Kazutoshi eventfully 30 days later. On hospi- acute renal failure and was started Yamada, MD, and Shogo Matsuda, tal day 64, he suddenly developed on continuous hemodiafiltration and MD. Published previously in Gastroen- fever, jaundice, and abdominal dis- mechanical ventilation. Computed terology (2016;151[1]:40-2). tention, followed by hypotension, tomography (CT) of the abdomen oliguria, and respiratory failure. showed marked ascites (Figure A, 78-year-old man was admit- Laboratory tests revealed the B), and a diagnostic paracentesis re- ted because of an exacerba- following: white blood cell count, vealed a dark, greenish-brown fluid A tion of interstitial pneumonia 44,300/mcL; serum albumin, 2.6 (Figure C) with a bilirubin level of and was started on steroid therapy. g/dL; aspartate aminotransferase, 14.8 mg/dL. On the next hospital day, he had a 1880 U/L; alanine aminotransferase, stroke. Because of persistent dys- 1096 U/L; bilirubin, 1.21 mg/dL; and The diagnosis is on page 40. tute AGA I nst AGA

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GLOBALACADEMYCME.COM/GASTROENTEROLOGY 2525-688COM_16-3 34 GI ONCOLOGY MARCH 2018 • GI & HEPATOLOGY NEWS A tool in early diagnosis PERSPECTIVE Blood test from page 1 What are the clinically relevant Therapeutics at Johns Hopkins Uni- Based on cancer stage, sensitivity questions answered by this test? versity, Baltimore, and his colleagues. for stage I cancers was 43%, for stage The report was published in Science. II 73%, and for stage III 78%. Again, olecular panels are here to additions to give this test a very CancerSEEK tests for mutations in sensitivity varied depending on cancer M stay – and the GI communi- promising first foray – did any- 2,001 genomic positions and eight type, with 100% sensitivity for stage ty will in some shape or form be body watch CNN? proteins. The researchers examined I liver cancer and 20% sensitivity for impacted, be it in performing di- While not ready for prime time, a 61-amplicon panel with each ampl- stage I esophageal cancer. agnostic procedures on test-pos- which is a tall order for a first icon analyzing an average of 33 base When tumor tissue samples from itive patients, or risk-stratifying report, the authors dutifully point pairs within a gene. They theorized 153 patients with statistically signifi- patients prior to testing. out the need for a pro- the test could detect between 41% cant ctDNA levels were analyzed, iden- The conceptual chal- spective real-life cohort and 95% of the tical mutations were lenge is that it is not validation. In the mean- cancers in the found in the plasma about what any given time, regardless of the Catalog of Somatic See related story on page 38 and tumor in 90% test measures – various outcome of this particu- Mutations in Can- (138) of all cases. panels use separate lar test, it is a repeated cer dataset. They The protein mark- combination of mark- reminder that we need next used multiplex-PCR techniques to ers in the CancerSEEK test might also ers from epigenetics to to stay abreast of the minimize errors associated with large be able to anatomically locate malig- DNA mutations as well advances and the details sequencing and identified protein bio- nancies. Using machine learning to as whole or truncated of each molecular test, markers for early stage cancers that analyze patients testing positive with proteins – but how well DR. JUNG especially with a likely may not release detectable ctDNA. CancerSEEK, the results narrowed the a specific test with its very diverse and distinct The researchers used the technol- source of the cancer to two possible somewhat arbitrarily chosen group of tests to choose from. ogy to examine blood samples from anatomical sites in approximately 83% components and cutoffs per- Many of us will be part of 1,005 patients with stage I (20%), of patients and to one anatomical site forms. And, more importantly, interpreting results and deter- stage II (49%), or stage III (31%) can- in approximately 63% of patients. Ac- what the clinical implications of mining further management. cers of the ovary, liver, stomach, pan- curacy was highest for colorectal can- positive or negative test results Just as with hereditary cancer creas, esophagus, colorectum, lung, or cer and lowest for lung cancer. are. And no one knows that. At genetic panel testing, our tech- breast prior to undergoing neoadju- As the study included otherwise least for now. nical ability may have stretched vant chemotherapy. Participants had healthy patients with known malignan- A recent report in Science from beyond our ability to fully un- a median age of 64 years (range of cies, the results need to be confirmed a group from the Ludwig Center derstand the implications. Many 22-93 years). The healthy controls did with prospective studies of incidence for Cancer Genetics at Johns Hop- questions will arise: What about not have a history of cancer, chronic cancer types in a large population. kins proposes a new cancer blood true false positives? False nega- kidney disease, autoimmune disease, Patients in the screening setting may test based on a very systematic tives? Intervals? Can such tests or high-grade dysplasia. have less advanced disease and other and thoughtful approach to in- replace other screening? How The sensitivity of the test ranged comorbidities that could impact the clude select mutations in cell-free to choose any given test over from 98% in ovarian cancer to 33% sensitivity and specificity of the Can- DNA and circulating proteins the other? Should tests be com- in breast cancer, but the specificity cerSEEK test, the researchers wrote. associated with various solid or- bined or alternated? The tests was greater than 99%, with only 7 The study was funded by multiple gan tumors. For validation, they will be technically refined and of 812 control participants having a sources including grants from the used healthy and advanced but are here to stay – we need to get positive result. “We could not be cer- National Institutes of Health. The nonmetastatic cancer cohorts. to work on finding answers to tain that the few ‘false positive’ indi- authors reported various disclosures Through stringent controls and a the clinically relevant questions. viduals identified among the healthy involving diagnostics and pharma- series of validations, the authors cohort did not actually have an as-yet ceutical companies. present a range of sensitivities Barbara Jung, MD, AGAF, is the undetected cancer, but classifying for the various cancer types with Thomas J. Layden Endowed Pro- them as false positives provided the [email protected] an impressive specificity. This is a fessor and chief of the division of most conservative approach to clas- technically very strong approach gastroenterology and hepatolo- sification and interpretation of the SOURCE: Cohen JD et al. Science 2018 with many nifty and thoughtful gy, University of Chicago. data,” the authors wrote. Jan 18. doi: 10.1126/science.aar3247. FDA approves lutetium Lu 177 dotatate for GEP-NETs

BY LORI LAUBACH tatate plus octreotide to octreotide control (hazard ratio, 0.21; 95% CI, lymphopenia, increased GGT, AST Frontline Medical News alone, and a subset of patients from 0.13-0.32; P less than .0001). There and/or ALT, vomiting, nausea, hyper- an expanded access program in the was a 48% reduction in the estimat- glycemia and hypokalemia. Serious he Food and Drug Administration Netherlands in patients with soma- ed risk of death with lutetium Lu side effects include myelosuppres- Thas approved the first radiophar- tostatin receptor positive tumors, the 177 dotatate treatment compared to sion, secondary myelodysplastic syn- maceutical, lutetium Lu 177 dotatate FDA said in a statement. treatment with octreotide alone at a drome and leukemia, renal toxicity, (Lutathera), for the treatment of The NETTER-1 study included preplanned interim overall survival hepatotoxicity, neuroendocrine hor- somatostatin receptor positive gastro- patients who had inoperable mid- analysis (HR, 0.52; 95% CI, 0.32- monal crises, and infertility. Patients enteropancreatic neuroendocrine tu- gut NETs progressing under stan- 0.84). taking lutetium Lu 177 dotatate are mors (GEP-NETs), including foregut, dard-dose octreotide treatment In the expanded access study, exposed to radiation; exposure of midgut, and hindgut neuroendocrine and overexpressing somatostatin complete or partial tumor shrinkage other patients, medical personnel, tumors in adults. receptors. The primary endpoint was was reported in 16% of the patients and household members should be Approval is based on two studies, met, showing a 79% reduction in in the subset of 360 patients with limited according to the FDA. including the phase 3, NETTER-1, risk of disease progression or death GEP-NETs. that compared lutetium Lu 177 do- in the study arm compared with the Common side effects include [email protected] 10/25/2017 11:12:53 AM GIHEP_35.indd 1 10/25/2017 11:14:44 AM GIHEP_36.indd 1 GIHEPNEWS.COM • MARCH 2018 GI ONCOLOGY 37 Cancer rates haven’t PERSPECTIVE What is holding back ‘quality’? budged despite ostcolonoscopy colorectal can- PCCRC rates essentially says, “If I Pcers (PCCRCs) are those can- am destined to develop CRC in the cers that occur between next 3 years, what is my colonoscopy quality efforts 6 and 36 months after a chance of a false-negative complete colonoscopy. colonoscopy?” The ques- BY HEIDI SPLETE 1997 to 870 per 10,000 people in Most of these cancers tion posed above yields Frontline Medical News 2010-2011. grow from cancers or “rates” that would terrify Comparing the 2006-2010 and near cancers missed patients (4%-10%) with- he number of colorectal cancers 1996-2001 time periods yielded ad- or incompletely resect- out a detailed explana- diagnosed after a colonoscopy justed odds of PCCRC, distal PCCRC, ed during the baseline tion (it took me about an Tremained consistent at approx- and proximal PCCRC of 1.14, 1.11, colonoscopy. Clinical hour of focused attention imately 8% over a 15-year period and 1.14, respectively; the trends researchers have pub- to finally understand despite the introduction of quality were not affected by endoscopist spe- lished extensively about DR. ALLEN this methodology). In es- improvement measures, according to cialty or institutional setting. reasons for missed lesions sence, if we could, a priori, data from a population-based cohort “Our findings are concerning for and we know that age, female sex, identify and examine only pa- study of more than 1 million individ- lack of improvement in colonoscopy and proximal location of cancers tients who have a prevalent can- uals in Canada. practice quality in Ontario, particu- increase rates of PCCRC. GI soci- cer or near cancer, how close can “It is believed that the majority of larly in the wake of greater emphasis eties worldwide have developed we come to 100% accuracy with a PCCRCs [postcolonoscopy colorec- having been placed on colonoscopy training initiatives, performance colonoscopy? Turns out, that rate tal cancers] arise due to cancers quality metrics during the study metrics (adenoma detection rate is somewhere between 90% and or near cancers that were either period,” the researchers said. The or ADR, withdrawal time, and 96% and really hasn’t changed missed or incompletely treated findings contrast with the decline in prep quality documentation), and over time. Thus, these studies during colonoscopy,” wrote Sanjay PCCRC rates in the United Kingdom postcolonoscopy guidelines, all in- speak to the impact of our efforts K. Murthy, MD, of the University of reported in a previous study of a sim- tended to mitigate risk of PCCRCs. around colonoscopy quality. Ottawa, and colleagues. ilar time period, they noted. It would be nice to know whether The discouraging conclusion Established quality improvement The study findings were limited by such efforts have made a differ- from Murthy’s analysis is that de- measures included adenoma de- several factors, including possible pa- ence. spite substantial efforts, false-neg- tection rate, cecal intubation rate, tient and outcome misclassification, Murthy and colleagues studied ative colonoscopy rates have colonoscopy withdrawal time, and and an unvalidated definition for PC- PCCRC rates in Ottawa, Canada, remained around 8% (in Ottawa) endoscopy training standards, but CRC. Although more research is need- during three different time peri- since 1996. Of note, this contrasts how well the measures have been ed in other jurisdictions to confirm, ods to determine whether quality with studies out of England, where implemented remains uncertain, the the results “call for increased popu- and educational efforts affected a national, focused quality im- researchers said. In a study published lation-based practice audit as well as PCCRC rates. More than 99% of provement effort has been ongoing in Gastrointestinal Endoscopy (2018 endoscopy educational programs and this population has health care for over a decade and has made Jan 6. doi: 10.1016/j.gie.2017.12.027), certification requirements.” covered under a single public pay- a dent (although slight) in PCCRC the researchers assessed data from The study was supported by a re- er system where all encounters rates. This is a provocative study 1,093,658 eligible adults aged 50-74 search grant to Dr. Murthy from the are tracked. Using population-lev- that deserves your attention. years over a 15-year period. The time University of Ottawa. The researchers el data derived from over 1 period was divided into three sec- had no conflicts to disclose. million people they identified can- John I. Allen MD, MBA, AGAF, pro- tions: July 1, 1996, to June 30, 2001; cers diagnosed within 36 months fessor of medicine, department of July 1, 2001, to June 30, 2006; and [email protected] of a colonoscopy and compared gastroenterology and hepatology, July 1, 2006, to Dec. 31, 2010. three 5-year periods (1996-2001, University of Michigan, Ann Arbor, The number of colonoscopies SOURCE: Murthy SK et al. Gastroin- 2001-2006, and 2006-2010). and Editor in Chief of GI & Hepatol- increased during the study period, test Endosc. 2018 Jan 6. doi: 10.1016/j. Their method of calculating ogy News. from 305 per 10,000 people in 1996- gie.2017.12.027. Colorectal cancer deaths Estimated colon and rectal cancer death rates for 2018 W. Va. projected for 2018 23.6

BY RICHARD FRANKI 2015 data from the National Center Frontline Medical News for Health Statistics. The expected number of deaths for Utah DC 9.0 olon and rectal cancer mor- 2018, coupled with a current popu- Ctality is expected to be about lation estimate of nearly 326 million, Deaths per 15.5/100,000 population in 2018, works out to an expected death rate 100,000 pop. with the highest rate in West Virginia of 15.5/100,000 population. The 18.6-23.6 news and the lowest in Utah. Census Bureau estimates for the state

16.1-18.4 edical Approximately 50,630 deaths populations and the deaths projected from colorectal cancer are predict- by the ACS produce expected death 13.5-15.7

ed for the year in the United States rates of 23.6/100,000 for West Vir- 9.0-13.2 rontline M by the American Cancer Society ginia and 9.0 for Utah. F (ACS) in its Cancer Facts & Figures Note: Based on 2001-2015 mortality data from the National Center for Health Statistics. 2018, based on analysis of 2001- [email protected] Source: American Cancer Society 38 GI ONCOLOGY MARCH 2018 • GI & HEPATOLOGY NEWS Circulating tumor cell assay promising for CRC screen

BY SUSAN LONDON – some with colorectal cancer, some breast, and lung cancer.” given some of the information we Frontline Medical News with precancerous lesions, and some The investigators are also iden- have from prior tests.” healthy. Results showed the assay’s tifying collaborators for testing the SAN FRANCISCO – A new blood- sensitivity was nearly 87% for cancer new assay among U.S. populations, Study details based assay that measures circulat- and 77% for precancerous lesions. he noted. Dr. Tsai’s team studied 327 patients ing tumor cells (CTCs) shows good Specificity exceeded 97%. “Screening tests offer some of the with colorectal cancer of all stages, performance in detecting colorectal “The CMx assay is capable of de- greatest potential for getting to zero 111 patients with precancerous cancer and precancer, investigators tecting … early-stage cancer with colorectal cancer deaths,” said invited lesions (adenomas, advanced adeno- reported at the 2018 GI Cancers a low false-positive rate. As it is a discussant Douglas A. Corley, MD, mas, carcinoma in situ/stage 0), and Symposium. blood test, higher compliance will PhD, AGAF, clinical professor and 182 healthy controls. All had blood Although colorectal cancer screen- drawn for the CTC assay before ing is a grade A recommendation undergoing colonoscopy. Results ews

of the U.S. Preventive Services Task n of each test were ascertained with Force, poor uptake remains prob- blinding to the results of the other. lematic and contributes to more edica L CTCs are rarely shed into the cir-

advanced disease at diagnosis, noted ine M culation from precancerous lesions, lead investigator Wen-Sy Tsai, MD, with approximate density of only 1 assistant professor at Linkou Chang per billion blood cells, Dr. Tsai said.

Gung Memorial Hospital, Taoyuan, ondon /F ront L The CMx assay (manufactured by Taiwan. CellMax Life) is able to detect these usan L

“Currently, one-third of Americans s cells with high sensitivity through have never been screened for col- use of advanced technologies such hotos

orectal cancer,” he said, due in part P as affinity-based microfluidics and to reluctance to undergo colonosco- Dr. Wen-Sy Tsai is assistant professor at Dr. Douglas A. Corley is clinical professor a biomimetic surface coating. py and poor compliance with stool Linkou Chang Gung Memorial Hospital, and gastroenterologist at the University of The assay is performed with just tests. Further complicating matters, Taoyuan, Taiwan. California, San Francisco. 2 mL of whole blood. CTCs are de- the fecal immunochemical test (FIT) fined as intact nucleated cells stain- has a high false-positive rate. lead to better outcomes,” Dr. Tsai gastroenterologist at the University ing positive for CD20 and negative He and his coinvestigators tested proposed. “Because the mechanism of California, San Francisco, and a re- for CD45; they were combined with the new assay, called CMx (CTCs in of CTC dissemination is similar, the search scientist at Kaiser Permanen- patient age in an algorithm, ulti- Maximum), among 620 individuals in CTC assay can be applied in oth- te, San Francisco. mately producing a risk score. Taiwan who underwent colonoscopy er cancer types such as prostate, CTCs are especially attractive for Study results showed that the screening because they could be both CTC assay had an accuracy of 87.9% sensitive and specific, he said. “Unlike in the entire cohort, reported Dr. something such as fecal immunotest- Tsai. The false-positive rate was just ing, which is not testing specifically 3.3%, and the false-negative rate AGA for cancer, or colonoscopy, which is was 15.8%. quite invasive and detects a lot of Sensitivity was 84.0% overall things that may (76.6% for never progress to precancer and ACADEMYOF See related story on page 34 cancer, CTCs offer 86.9% for can- this potential,” cer), specificity said Dr. Corley. was 97.3% over- EDUCATORS Challenges of interpreting new all (97.3% and 97.3%), and area A PROGRAM OF THE AGA INSTITUTE screening tests include their heavy under the receiver operating char- dependence on the population being acteristic curve was 0.87 overall Join the home for educators tested and the need for replication, (0.84 and 0.88). within AGA and enhance your according to Dr. Corley. For exam- Dr. Tsai noted that the CTC assay’s ple, initial results for the septin 9 sensitivity of nearly 77% for precan- teaching skills. The academy methylated DNA blood test looked cer compares favorably with that of a provides support, academic very good, with sensitivity of about variety of other screening tests, such 90% (BMC Med. 2011;9:133), but as the stool guaiac test for fecal occult promotion, funding and more. after its testing in 14 populations, a blood (2%-10%), FIT alone (23.8%), meta-analysis showed that pooled and a stool DNA test combined with sensitivity was just 67% (Biomed FIT (42%), and, in fact, falls within Rep. 2017;7[4]:353-60). the range reported for colonoscopy WATCH YOUR “Circulating tumor markers are (76%-94%). an incredibly interesting target The symposium was sponsored for screening, particularly because by the American Gastroenterological CAREER TAKE OFF of their potential for being very Association, the American Society for specific for what you are looking Clinical Oncology, the American So- for, and potentially markedly de- ciety for Radiation Oncology, and the Join at creasing the subsequent follow-up Society of Surgical Oncology. that would need to be done for www.gastro.org/academygrants. invasive tests such as colonoscopy,” [email protected] Dr. Corley said. “However, this [CTC

2200-086EDU_17-4 assay] really requires confirmation SOURCE: Tsai W et al., ASCO GI Ab- in screening populations, especially stract 556. GIHEPNEWS.COM • MARCH 2018 AGA GUIDELINE 39 AGA Guideline: Use goal-directed fluid therapy, early oral feeding in acute pancreatitis

BY AMY KARON grade cholangiopancreatography infected peripancreatic necrosis, the high likelihood of benefit from Frontline Medical News (ERCP) for patients with acute multiorgan failure, and total nec- early versus delayed cholecystecto- pancreatitis. The authors note rotizing pancreatitis, the authors my in this patient population,” the atients with acute pancreatitis that no evidence supports routine wrote. In another 12 trials, enteral experts stated. should receive “goal-direct- prophylactic antibiotics for acute nutrition significantly reduced Patients with biliary pancre- Ped” fluid therapy with normal pancreatitis patients without chol- the risk of infected peripancreatic atitis should be evaluated for saline or Ringer’s lactate solution angitis, and that urgent ERCP did necrosis, single-organ failure, and cholecystectomy during the same rather than hydroxyethyl starch not significantly affect the risk of multiorgan failure compared with admission, while those with alco- (HES) fluids, states a new guideline mortality, multiorgan failure, sin- parenteral nutrition. hol-induced pancreatitis should re- from the AGA Institute. gle-organ failure, infected pancre- Clinicians continue to debate ceive a brief alcohol intervention, In a single-center randomized atic and peripancreatic necrosis, cholecystectomy timing in patients according to the guidelines, which trial, hydroxyethyl starch fluids or necrotizing pancreatitis in eight with biliary or gallstone pancre- also call for better studies of how conferred a 3.9-fold increase in the alcohol and tobacco cessation mea- odds of multiorgan failure (95% sures affect risk of recurrent acute confidence interval for odds ratio, pancreatitis, chronic pancreatitis, 1.2-12.0) compared with normal The guideline defines goal-directed fluid therapy as titration and pancreatic cancer, as well as saline in patients with acute pan- based on meaningful targets, such as heart rate, mean quality of life, health care utiliza- creatitis, wrote guideline authors tion, and mortality. Seth D. Crockett, MD, MPH, of the arterial pressure, central venous pressure, urine output, The authors also noted knowl- University of North Carolina, Chap- blood urea nitrogen concentration, and hematocrit. edge gaps concerning the relative el Hill, and his associates. This trial benefits of risk stratification tools, and another randomized study the use of prophylactic antibiot- found no mortality benefit for HES ics in patients with severe acute compared with fluid resuscitation. randomized controlled trials of atitis. The guidelines strongly pancreatitis or necrotizing pan- The evidence is “very low quality” patients with acute gallstone pan- recommend same-admission creatitis, and the timing of ERCP but mirrors the critical care lit- creatitis. cholecystectomy, citing a random- in patients with severe biliary erature, according to the experts. The guideline strongly recom- ized controlled trial in which this pancreatitis with persistent biliary So far, Ringer’s lactate solution mends early oral feeding and approach markedly reduced the obstruction. and normal saline have shown enteral rather than parenteral nu- combined risk of mortality and gall- The guideline was developed by similar effects on the risk of organ trition for all patients with acute stone-related complications (OR, the AGA Institute. The authors dis- failure, necrosis, and mortality, pancreatitis. In 11 randomized 0.2; 95% CI, 0.1-0.6), readmission closed no conflicts of interest. but ongoing trials should better controlled trials, early and de- for recurrent pancreatitis (OR, 0.3; clarify this choice, they noted (Gas- layed feeding led to similar rates 95% CI, 0.1-0.9), and pancreati- [email protected] troenterology. doi: 10.1053/j.gas- of mortality, but delayed feeding cobiliary complications (OR, 0.2; tro.2018.01.032). produced a 2.5-fold higher risk of 95% CI, 0.1-0.6). “The AGA issued a SOURCE: Crockett SD et al. Gas- The guideline addresses the ini- necrosis (95% CI for OR, 1.4-4.4) strong recommendation due to the troenterology. doi: 10.1053/j.gas- tial 2-week period of treating acute and tended to increase the risk of quality of available evidence and tro.2018.01.032. pancreatitis. It defines goal-direct- ed fluid therapy as titration based on meaningful targets, such as heart rate, mean arterial pressure, central venous pressure, urine out- put, blood urea nitrogen concen- tration, and hematocrit. Studies of Exceptional goal-directed fluid therapy in acute pancreatitis have been unblinded, Editorial Fellowship have used inconsistent outcome measures, and have found no defi- Opportunity nite benefits over nontargeted fluid therapy, note the guideline authors. Nevertheless, they condi- Gastroenterology, AGA’s flagship journal, is accepting tionally recommend goal-directed applications for a one-year editorial fellowship fluid therapy, partly because a ran- beginning in July 2018. Those entering their second domized, blinded trial of patients and third year of GI fellowship, as well as PhDs fewer with severe sepsis or septic shock than two years out of training, are invited to apply. (which physiologically resembles Deadline for applications is Wednesday, April 18. acute pancreatitis) had in-hospital mortality rates of 31% when they received goal-directed fluid ther- apy and 47% when they received standard fluid therapy (P = .0009). Apply today at www.gastro.org/GastroFellowship. The guideline recommends against routine use of two inter- ventions: prophylactic antibiotics 2150-310PUB_17-5 and urgent endoscopic retro- 40 PRACTICE MANAGEMENT MARCH 2018 • GI & HEPATOLOGY NEWS Doctors to Congress: Keep Part B drug payments out of MIPS adjustment

BY GREGORY TWACHTMAN American Society of Clinical Oncol- specialists administer more Part therefore, may be exposed to sig- Frontline Medical News ogy. B drugs than other specialists, ac- nificant financial risk and payment Under MIPS, physicians are scored cording to health care consultancy swings year-over-year under the CMS hysician specialists are calling based on their performance across Avalere Health. proposal,” John Feore, director at on Congress to isolate Medicare three categories: quality, improve- For gastroenterologists, the pri- Avalere, said in a statement. PPart B drug reimbursements ment activities, and advancing care mary concern with the application In 2018, physicians in those spe- from payment adjustments under information. A fourth category, cost, of the MIPS payment adjustment to cialties could see drug payments the Merit-Based Incentive Payment is planned but not yet included in the Part B drugs is patient access to the increase or decrease by as much as System (MIPS). score (although cost doesn’t impact biologics and biosimilars used to 16%, according to Avalere research. A coalition of medical societies, adjustments until 2020, it is part of treat inflammatory bowel disease The policy likely will have an large group practices, and patient the 2018 program year). Medicare including Crohn’s disease and ul- even greater effect on smaller prac- advocacy groups has asked for an “in- payments, which currently include cerative colitis. Under CMS’s policy, tices and those in rural settings and tervention this year with a technical Part B drug reimbursements, are sub- gastroenterologists facing a penalty could lead to access issues, accord- correction that ensures the [MIPS] ject to bonuses and penalties based or negative payment adjustment ing to the coalition letter. score adjustment is not applied to on performance scores. may have Part B drug payments fall “Some patients already face access Part B drug payments,” according to In their November 2017 update to below what it costs to buy the Part challenges because the budget se- a Jan. 18 letter sent to the leaders of the Quality Payment Program, which B drug. Since Medicare payment for quester has eroded reimbursements the Senate Finance Committee, House includes MIPS, officials at the Centers Part B drugs is based on average to physicians, and this policy would Energy and Commerce Committee, for Medicare & MedicaidServices sales price, affected practices are exacerbate these problems,” the letter and the House Ways and Means (CMS) said they would be moving more likely to be small, have a small- states. “Patients would be left with Committee. “Since the 2018 MIPS forward with including Part B drug er number of patients on a Part B fewer locations where they could year has begun, it is imperative that payments in the MIPS adjustment. drug or prescribe a broader range receive care, resulting in less access Congress acts quickly to ensure that “This application of the adjustment of Part B drugs to patients. As MIPS and higher costs. A growing number patient access to critical treatments is ... is a significant departure from payment adjustments increase each of patients would then have to seek not negatively impacted.” current policy and would dispropor- year, the impact of the policy is ex- care in a hospital, which would result Among the groups signing the tionately affect certain specialties,” pected to touch more practices and in higher out-of-pocket expenses and, letter are the American Academy of according to the coalition’s letter. bring larger deficits, further eroding particularly in rural communities, Dermatology, American Gastroen- Certain specialties, including access to the biologics and biosimi- may require traveling longer distanc- terological Association, American rheumatology, oncology, and oph- lars used to treat IBD. es to receive care.” College of Rheumatology, American thalmology, have more to lose under “Certain specialists administer Academy of Neurology, and the the current policy because these more Part B drugs than others and, [email protected] CLINICAL CHALLENGES AND IMAGES The diagnosis (subacute), localized peritonitis and perichole- B Answer to “What is your diagnosis?” on cystic abscess; and type III (chronic), cholecys- page 33: Spontaneous gallbladder perforation toenteric fistula. These classifications are still o definite site of perforation was observed in use. Our patient had a type I perforation. The Nin the biliary tract by CT. However, with a most common site of perforation is the fundus suspicion of biliary tract perforation, 3-dimen- because of its poor blood supply. Predisposing sional drip-infusion CT cholangiography was factors for spontaneous gallbladder perfora- performed, which revealed a leakage of contrast tion include cholelithiasis, infections, diabetes medium from the gallbladder fundus (Figure D, mellitus, atherosclerosis, and steroid therapy, arrow) into the subhepatic space, leading to a which was observed in the present case. The diagnosis of spontaneous gallbladder perforation. diagnosis is suggested by ultrasonography, CT, Endoscopic retrograde cholangiography con- magnetic resonance imaging, endoscopic retro- firmed the perforation at the same site (Figure E, grade cholangiography, or cholescintigraphy. As F, arrows). An endoscopic nasobiliary drainage observed in the present case, drip-infusion CT tube was placed, and bile was aspirated contin- cholangiography provides high-quality images uously. Four weeks later, when the general con- of the biliary system; however, the availability dition of the patient stabilized, cholecystectomy of intravenous cholangiographic contrast media was performed. Histologic examination showed a is limited to a few countries.3 The difficulties in tute 3-mm perforation in the gallbladder fundus with diagnosis cause a delay in treatment and lead to

marked necrosis of the gallbladder wall associ- high morbidity and mortality. Gallbladder per- I nst AGA ated with chronic cholecystitis. No stones were foration should be considered as a differential found. He had an uneventful recovery and was diagnosis in patients presenting with peritonitis 2. Niemeier, O.W. Acute free perforation of the discharged in an improved condition. with an unknown etiology. gall-bladder. Ann Surg. 1934;99:922-4. Gallbladder perforation is a rare but 3. Hyodo, T., Kumano, S., Kushihata, F. et al. CT life-threatening complication of cholecystitis References and MR cholangiography: advantages and pit- with or without stones, with a recently reported 1. Ausania, F., Guzman Suarez, S., Alvarez Gar- falls in perioperative evaluation of biliary tree. mortality rate of 9.5%.1 Niemeier2 classified the cia, H. et al. Gallbladder perforation: morbidity, Br J Radiol. 2012;85:887-96. condition into three types: type I (acute), free mortality and preoperative risk prediction. perforation and generalized peritonitis; type II Surg Endosc. 2015;29:955-60. [email protected] GIHEPNEWS.COM • MARCH 2018 PRACTICE MANAGEMENT 41 PRACTICE MANAGEMENT TOOLBOX: Making social media work for your practice

BY DARRELL M. GRAY II, MD, MPH, AND combined experience. We initially form(s) of choice. For example, on DEBORAH A. FISHER, MD, MHS, AGAF presented these strategies during Facebook and Twitter, you can select a Meet-the-Professor Luncheon at an option that requests your per- ocial media use is ubiquitous Digestive Disease Week® in Chicago mission before a friend or follower and, in the digital age, it is the (http://www.ddw.org/education/ is added to your network. You also Sascendant form of communica- session-recordings). can tailor who (such as friends or fol- tion. Individuals and organizations, First, establish personal objec- lowers only) can access your posted digital immigrants (those born before tives and/or goals for using social content directly. However, know that the widespread adoption of digital media. It is with these in mind that your content still may be made public technology), and digital natives alike DR. GRAY DR. FISHER you select social media platforms if it is shared by one of your friends are leveraging social media platforms, on which to create a digital profile or followers. such as blogs, Facebook, Twitter, You- the 69 participants, one-third report- and footprint. They also can serve Fourth, nurture your social media Tube, and LinkedIn, to curate, con- ed using at least one social media as guiding principles for the content presence by sharing credible content sume, and share information across platform multiple times per day and that you share and individuals or deliberately, regularly, and, when ap- the spectrum of demographics and 56% expressed interest in expanding groups with whom you engage. For propriate, with attribution. target audiences. In the United States, their social media presence. Chiang example, if your goals include dis- Fifth, diversify your content within 7 in 10 Americans are using social et al.9 even developed GI hashtag seminating evidence-based content the realm of your predefined objec- media and, although young adults ontology (hashtag refers to a phrase on liver diseases to a broad audience tives and/or goals and avoid a sin- were early adopters, use among older that is preceded by # and is used to and connecting with a network of key gular focus of self-promotion or the adults is increasing rapidly.1 identify and collate topics of inter- opinion leaders and patient-oriented appearance of self-promotion. Top so- Furthermore, social media has est, i.e., #coloncancer) as a means groups who share this interest and/ cial media users suggest, and the au- cultivated remarkable opportunities to allow lay and health professional or expertise, Twitter may be an ideal thors agree, that your content should in the dissemination of health in- social media users to curate medical option for you given its vast user be only 25%-33% of your posts. formation and disrupted traditional information more easily. These data base and flexibility in both posting Sixth, thoroughly vet all content methods of patient–provider com- are particularly interesting in light multimedia content such as pictures, that you share. Avoid automatically munication. The days when medically of studies suggesting that patients videos, and links to publications, and sharing articles or posts because of trained health professionals were the with inflammatory bowel disease tailoring the content you receive to a catchy headline. Read them before gatekeepers of health information and chronic viral hepatitis, chronic specific individuals and groups. you post them. There may be details are long gone. Approximately 50% of diseases that commonly are managed Second, find a mentor to provide buried in them that are not credible Americans seek health information by GI and hepatology providers, use hands-on advice. This is particularly or with which you disagree. online before seeing a physician.2 social media in the management of true if your general familiarity with Seventh, build community by con- Patients and other consumers regu- their disease. Patients with these the social media platforms is limited. necting and engaging with other us- larly access social media to search for conditions also value interaction with If this is not available through your ers on your social media platform(s) information about diseases and treat- health care professionals on social network of colleagues or workplace, of choice. ments, engage with other patients, media.10,11 we recommend exploring opportu- Eighth, integrate multiple media identify providers, and to express or There is ample opportunity to close nities offered through your profes- (i.e., photos, videos, infographics) rate their satisfaction with providers, the gap between patient and health sional organization(s) such as the and/or social media platforms (i.e., clinics, and health systems.3-5 In ad- care provider engagement in social aforementioned Meet-the-Professor embed link to YouTube or a website) dition, they trust online health infor- media, equip providers with the tools Luncheon at DDW. to increase engagement. mation from doctors more than that they need to be competent consumers Third, know the privacy setting Ninth, adhere to the code of ethics, from hospitals, health insurers, and and sharers of information in this dig- options on your social media plat- Continued on following page drug companies.6 Not surprisingly, ital exchange, and increase the pool of this has led to tremendous growth evidence-based information on GI and Table 1. Examples of social media metrics to include in dossier in use of social media by health care liver diseases on social media.12 How- for promotion and tenure providers, hospitals, and health cen- ever, there is limited published litera- ters. More than 90% of U.S. hospitals ture tailored to GIs and hepatologists. Demonstration of excellence have a Facebook page and 50% have The goal of this article, therefore, is Evidence of recognition for expertise in clinical field. a Twitter account.7 to provide a broad overview of best Peer-reviewed and non–peer-reviewed publications. Although adoption of social me- practices in the professional use of so- Collaborations within and/or outside of your institution resulting from social media dia has been slow among GIs and cial media and highlight examples of engagement. hepatologists, it is growing. In a novel applications in clinical practice. Data supporting excellence in clinical care, teaching, and/or leadership from social study published in 2015, Davis et al.8 media engagement. found that only 48% of GI providers Getting started and maintaining Demonstration of reputation reported never using social media. a presence on social media Evidence of being a key opinion leader. More recently, in March 2017, we Social media can magnify your pro- Invited lectures at local, regional, national, and/or international meetings, webinars, or conducted a survey of AGA members fessional image, amplify your voice, podcasts. subscribed to the AGA eDigest. Of and extend your influence much Invitations to serve on national committees. faster than other methods. It also can Media requests and quotes. Content from this column was be damaging if not used responsibly. Demonstration of impact originally published in the Thus, we recommend the following Evidence of activities or innovations that positively influenced the clinical or research “Practice Management: The approaches to responsible use of practice within field of expertise. Road Ahead” section of Clinical social media and to cultivating your Feedback from followers on value of social media posts. Gastroenterology and Hepatolo- social media presence based on Development and implementation of policy, curricula, or practices within an institution gy (2017;15[11]:1651-4). current evidence, professional orga- and/or professional organization. nizations’ policy statements, and our Awards or recognition related to social media engagement. 42 PRACTICE MANAGEMENT MARCH 2018 • GI & HEPATOLOGY NEWS

Continued from previous page for GI health providers for maintain- social media accounts because they ing a digital footprint on social media rarely truly are private. Take-away points governance, and privacy of the pro- that reflects the ethical and profes- Third, avoid providing specific 1. Social media is a useful tool for fession and of your employer. sional standards of the field. medical recommendations to individ- curation and dissemination of First, avoid sharing information uals. This creates a patient–provider health information. Best practices: Privacy and that could be construed as a patient relationship and legal duty. Instead, 2. Familiarize yourself with the governance in patient-oriented identifier without documented con- recommend consultation with a social media policies of your em- communication on social media sent. This includes, but is not lim- health care provider and consider ployer and professional societies’ Two factors that have been of pivotal ited to, an identifiable specimen or providing a link to general informa- recommendations for profes- concern with the adoption of social photograph, and stories of care, rare tion on the topic (e.g., AGA informa- sionalism online. media in the health care arena and conditions, and complications. Note tion for patients at www.gastro.org/ 3. Be deliberate about nurturing led to many health care professionals that dates and location of care can patientinfo). your social media presence via being laggards as opposed to early lead to identification of a patient or Fourth, declare conflicts of interest, regularly sharing credible con- adopters are privacy and governance. care episode. if applicable, when sharing informa- tent and engaging other users. Will it violate the patient–provider Second, recognize that personal tion involving your clinical, research, 4. Social media can be used ef- relationship? What about the Health and professional online profiles are and/or business practice. fectively to promote the value of Insurance Portability and Account- discoverable. Many advocate for Fifth, routinely monitor your online your work in clinical care, med- ability Act? How do I maintain separating the two as a means of presence for accuracy and appropri- ical education, research, and/or boundaries between myself and the shielding the public from elements of ateness of content posted by you and academic promotion. public? These are just a few of the a private persona (i.e., family pictures by others in reference to you. Know questions that commonly are asked and controversial opinions). However, that our profession’s ethical stan- by those who are unfamiliar with the capacity to share and find com- dards for behavior extend to social social media etiquette for health care ments and images on social media is media and we can be held account- as a complement to the traditional re- professionals. We highly recommend much more powerful than the privacy able to colleagues and our employer quirements that were in their dossier, reviewing the position paper regard- settings on the various social media if we violate them. and leveraged them to a promotion ing online medical professionalism platforms. If you establish distinct Many employers have become sav- from assistant to associate profes- issued by the American College of personal and professional profiles, ex- vy to issues of governance in use of sors.16,17 Examples are provided in Physicians and the Federation of ercise caution before accepting friend social media and institute policy rec- Table 1. State Medical Boards as a starting or follow requests from patients on ommendations to which employees point.13 We believe the following to your personal profile. In addition, be are expected to adhere. If you are an Summary be contemporary guiding principles cautious with your posts on private employee, we recommend checking We have outlined why you should with your marketing and/or human consider establishing and maintain- resources department(s) about this. ing a professional presence on social media and how to accomplish this. CLASSIFIEDS Novel applications for social You will have a smoother experience media in clinical practice if you learn your local rules and poli- Also available at MedJobNetwork.com Social media has been shown to be cies and abide by our suggestions to PROFESSIONAL OPPORTUNITIES an effective medium for medical edu- avoid adverse outcomes. You will be cation through virtual journal clubs, most effective if you establish goals moderated discussions or chats, and for your social media participation video sharing for teaching proce- and revisit these goals over time for WHERE A LANDSCAPE OF dures, to name a few applications. So- continued relevance and success and cial media is used to collect data via if you have consistent and valuable OPPORTUNITIES AWAITS A polls or surveys, and to disseminate output that will support attainment GASTROENTEROLOGIST and track the views and downloads of these goals. Welcome to the GI of published works. It is also a source social media community! Be sure to for unsolicited, real-time feedback on follow Clinical Gastroenterology and Gundersen Health System in La Crosse, Wisconsin patient experience and engagement, Hepatology and the AGA on Face- is seeking a BC/BE Gastroenterologist to join its established medical team. and, more simply, for solicited feed- book (facebook.com/cghjournal and back for patient satisfaction ratings. facebook.com/amergastroassn) and Practice in our state-of-the-art Endoscopy Center Academic institutions increasingly Twitter (@AGA_CGH and @Amer- and modern outpatient clinic. Outreach services are are recognizing social media scholar- GastroAssn), and the coauthors (@ provided at our satellite clinics located within an easy drive from La Crosse. In addition, you will have ly activities and their broad-reaching DMGrayMD and @DrDeborahFisher) opportunities for clinical research and will be influence on the mission of educa- on Twitter. actively involved in teaching our Surgical, tion, research, and patient care, but Transitional, and Internal Medicine residents. have been slow to acknowledge them References You’ll join a physician-led, not-for-profit health as academic currency. The Mayo 1. Social Media Fact Sheet. Pew Research system with a top-ranked teaching hospital and Clinic is a forerunner in developing a Center [updated January 12, 2017]. Avail- one of the largest multi-specialty group practices framework for the incorporation of able from http://www.pewinternet.org/ with about 700 physicians and associate medical staff. Visit gundersenhealth.org/MedCareers social media scholarship into promo- fact-sheet/social-media/. Accessed: June 20, tion and tenure criteria.14 They have 2017. Send CV to Kalah Haug established a Social Media Network 2. Hesse B.W., Nelson D.E., Kreps G.L., et al. Medical Staff Recruitment through which they develop best Trust and sources of health information: the Gundersen Health System [email protected] practices and train physicians and impact of the Internet and its implications 15 or call (608)775-1005. staff. However, there are examples for health care providers: findings from the of physicians who do not work in en- first Health Information National Trends vironments that include social media Survey. Arch Intern Med. 2005;165:2618- engagement in promotion and tenure 24.

EEO/AA/Veterans/Disabilities criteria, but who individually estab- 3. Moorhead S.A., Hazlett D.E., Harrison lished metrics of their social media L., et al. A new dimension of health care: influence and impact, included them systematic review of the uses, benefits, GIHEPNEWS.COM • MARCH 2018 PRACTICE MANAGEMENT 43 and limitations of social media for health mayo-clinic-includes-social-media-scholar- promoted in academic medicine. Avail- engagement and equity in digestive communication. J Med Internet Res. ship-activities-in-academic-advancement/ able from http://www.kevinmd.com/ health, The Ohio University College of 2013;15:e85. Date: May 26, 2016. Accessed: July 1, 2017. blog/2016/10/used-twitter-get-promot- Medicine, Athens, Ohio; Dr. Fisher is 4. Chou W.Y., Hunt Y.M., Beckjord E.B. et al. 16. Freitag C.E., Arnold M.A., Gardner J.M., ed-academic-medicine.html. Date: October associate director, gastroenterology Social media use in the United States: im- et al. If you are not on social media, here’s 9, 2016. Accessed: July 1, 2017. research, Duke Clinical Research Insti- plications for health communication. J Med what you’re missing! #DoTheThing. Arch tute, director of social and digital me- Internet Res. 2009;11:e48. Pathol Lab Med. 2017; (Epub ahead of Dr. Gray is medical director, endoscopy dia Duke GI, Duke University, Durham, 5. Chretien K.C., Kind T. Social media and print). and gastroenterology services, Univer- N.C. The authors disclose no conflicts clinical care: ethical, professional, and social 17. Stukus D.R. How I used twitter to get sity Hospital, director of community of interest. implications. Circulation. 2013;27:1413-21. 6. Social Media ‘likes’ Healthcare. PwC Health Research Institute; 2012. Avail- able from https://www.pwc.com/us/en/ health-industries/health-research-insti- tute/publications/pdf/health-care-social- media-report.pdf. Accessed: June 20, 2017. 7. Griffis H.M., Kilaru A.S., Werner R.M., et al. Use of social media across US hospitals: descriptive analysis of adoption and utiliza- tion. J Med Internet Res. 2014;16:e264. 8. Davis E.D., Tang S.J., Glover P.H., et al. Impact of social media on gastroenterol- ogists in the United States. Dig Liver Dis. 2015;47:258-9. IMPORTANT SAFETY INFORMATION 9. Chiang A.L., Vartabedian B., Spiegel B. SUPREP® Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults. Most Harnessing the hashtag: a standard ap- common adverse reactions (>2%) are overall discomfort, abdominal distention, abdominal pain, nausea, vomiting and headache. proach to GI dialogue on social media. Am J Use is contraindicated in the following conditions: gastrointestinal (GI) obstruction, bowel perforation, toxic colitis and toxic megacolon, gastric retention, ileus, known allergies to components of the kit. Use Gastroenterol. 2016;111:1082-4. caution when prescribing for patients with a history of seizures, arrhythmias, impaired gag reflex, regurgitation or aspiration, severe active ulcerative colitis, impaired renal function or patients taking medications 10. Reich J., Guo L., Hall J., et al. A survey that may affect renal function or electrolytes. Use can cause temporary elevations in uric acid. Uric acid fluctuations in patients with gout may precipitate an acute flare. Administration of osmotic laxative products of social media use and preferences in may produce mucosal aphthous ulcerations, and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Patients with impaired water handling who experience severe vomiting should be closely monitored including measurement of electrolytes. Advise all patients to hydrate adequately before, during, and after use. Each bottle must be diluted with water to a final volume of 16 ounces patients with inflammatory bowel disease. and ingestion of additional water as recommended is important to patient tolerance. Inflamm Bowel Dis. 2016;22:2678-87. 11. Timms C., Forton D.M., Poullis A. Social media use in patients with inflammatory BRIEF SUMMARY: Before prescribing, please see Full Prescribing Information and Medication Guide for SUPREP® Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution. bowel disease and chronic viral hepatitis. INDICATIONS AND USAGE: An osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults. CONTRAINDICATIONS: Use is contraindicated in the following Clin Med. 2014;14:215. conditions: gastrointestinal (GI) obstruction, bowel perforation, toxic colitis and toxic megacolon, gastric retention, ileus, known allergies to components of the kit. WARNINGS AND PRECAUTIONS: 12. Prasad B. Social media, health care, and SUPREP Bowel Prep Kit is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults. Use is contraindicated in the following conditions: gastrointestinal (GI) obstruction, social networking. Gastrointest Endosc. bowel perforation, toxic colitis and toxic megacolon, gastric retention, ileus, known allergies to components of the kit. Use caution when prescribing for patients with a history of seizures, arrhythmias, impaired 2013;77:492-5. gag reflex, regurgitation or aspiration, severe active ulcerative colitis, impaired renal function or patients taking medications that may affect renal function or electrolytes. Pre-dose and post-colonoscopy ECGs should be considered in patients at increased risk of serious cardiac arrhythmias. Use can cause temporary elevations in uric acid. Uric acid fluctuations in patients with gout may precipitate an acute flare. 13. Farnan J.M., Snyder Sulmasy L., Worster Administration of osmotic laxative products may produce mucosal aphthous ulcerations, and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Patients with impaired water B.K., et al. Online medical professionalism: handling who experience severe vomiting should be closely monitored including measurement of electrolytes. Advise all patients to hydrate adequately before, during, and after use. Each bottle must be diluted patient and public relationships: policy with water to a final volume of 16 ounces and ingestion of additional water as recommended is important to patient tolerance.Pregnancy: Pregnancy Category C. Animal reproduction studies have not been statement from the American College of Phy- conducted. It is not known whether this product can cause fetal harm or can affect reproductive capacity. Pediatric Use: Safety and effectiveness in pediatric patients has not been established. Geriatric sicians and the Federation of State Medical Use: Of the 375 patients who took SUPREP Bowel Prep Kit in clinical trials, 94 (25%) were 65 years of age or older, while 25 (7%) were 75 years of age or older. No overall differences in safety or effectiveness of SUPREP Bowel Prep Kit administered as a split-dose (2-day) regimen were observed between geriatric patients and younger patients. DRUG INTERACTIONS: Oral medication administered Boards. Ann Intern Med. 2013;158:620-7. within one hour of the start of administration of SUPREP may not be absorbed completely. ADVERSE REACTIONS: Most common adverse reactions (>2%) are overall discomfort, abdominal distention, 14. Cabrera D., Vartabedian B.S., Spinner abdominal pain, nausea, vomiting and headache. Oral Administration: Split-Dose (Two-Day) Regimen: Early in the evening prior to the colonoscopy: Pour the contents of one bottle of SUPREP R.J., et al. More than likes and tweets: cre- Bowel Prep Kit into the mixing container provided. Fill the container with water to the 16 ounce fill line, and drink the entire amount. Drink two additional containers filled to the 16 ounce line with water over the ating social media portfolios for academic next hour. Consume only a light breakfast or have only clear liquids on the day before colonoscopy. Day of Colonoscopy (10 to 12 hours after the evening dose): Pour the contents of the second promotion and tenure. J Grad Med Educ. SUPREP Bowel Prep Kit into the mixing container provided. Fill the container with water to the 16 ounce fill line, and drink the entire amount. Drink two additional containers filled to the 16 ounce line with water over the next hour. Complete all SUPREP Bowel Prep Kit and required water at least two hours prior to colonoscopy. Consume only clear liquids until after the colonoscopy. STORAGE: Store at 20°-25°C 2017;9:421-5. (68°-77°F). Excursions permitted between 15°-30°C (59°-86°F). Rx only. Distributed by Braintree Laboratories, Inc. Braintree, MA 02185. 15. Cabrera D. Mayo Clinic includes social media scholarship activities in academic advancement. Available from https:// socialmedia.mayoclinic.org/2016/05/25/

INDEX OF ADVERTISERS For additional information, please call 1-800-874-6756 or visit www.suprepkit.com AbbVie Inc. MAVYRET 35-36 Braintree Laboratories, Inc. SUPREP 43-44 ©2017 Braintree Laboratories, Inc. All rights reserved. HH13276AT-U May 2017 Gilead Sciences, Inc Harvoni/Epclusa 15-21 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Reflixis 26-31 Olympus America Inc, EVIS EXERA III 11 Takeda Pharmaceuticals America, Inc. Entyvio 2-5 # 1 MOST PRESCRIBED, BRANDED BOWEL PREP KIT1

2

FIVE-STAR EFF1CACY WITH SUPREP ¨

Distinctive results in all colon segments

• SUPREP Bowel Prep Kit has been FDA-approved as a split-dose oral regimen3

• 98% of patients receiving SUPREP Bowel Prep Kit had “good” or “excellent” bowel cleansing2*†

• >90% of patients had no residual stool in all colon segments2*†

These cleansing results for the cecum included 91% of patients2*†

Aligned with Gastrointestinal Quality Improvement Consortium (GIQuIC) performance target of ≥85% quality cleansing for outpatient colonoscopies.4

*This clinical trial was not included in the product labeling. †Based on investigator grading. References: 1. IMS Health, NPA Weekly, May 2017. 2. Rex DK, DiPalma JA, Rodriguez R, McGowan J, Cleveland M. A randomized clinical study comparing reduced-volume oral sulfate solution with standard 4-liter sulfate-free electrolyte lavage solution as preparation for colonoscopy. Gastrointest Endosc. 2010;72(2):328-336. 3. SUPREP Bowel Prep Kit [package insert]. Braintree, MA: Braintree Laboratories, Inc; 2012. 4. Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Gastrointest Endosc. 2015;81(1):31-53.

©2017 Braintree Laboratories, Inc. All rights reserved. HH13276AT-U May 2017

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