mdedge.com/gihepnews

February 2021 Volume 15 / Number 2 COVID-19 vaccines: INSIDE FROM THE AGA Are they safe for JOURNALS Pruritus in cholangiopathies immunocompromised Bezafibrate seems able

arolina to help with “worst itch c possible.” • 6

orth patients? n of

BY ROXANNE NELSON, dose administration of the RN, BSN niverSity

/U MDedge News vaccine has been pegged Lessons in feeding at 95.0%, and the FDA has tubes trickland

S - said that the 95% credible Training might not have

rian covered it all. • 12 B Cality,oronavirus as they vaccines are interval for the vaccine Dr. Anne F. Peery, of University of North Carolina, Chapel Hill, have become a re clinicalefficacy trials,was 90.3%-97.6%. whether for recommends against surgery in certain patients. authorized for use in a But as with many initial GI ONCOLOGY growingnow being number approved of coun- and populations were repre- CRC in younger adults AGA Clinical Practice Update tries including the United senteddrugs or in vaccines, the trial cohort,not all Rates may be lower in adults under 50 than previously reported. • 15 Medical management of issuedStates. emergencyThe U.S. Food autho- and including individuals who rizationDrug Administration for the use of has the isare largely immunocompromised. unknown how ENDOSCOPY - As of December 2020, it- DOACs in elective colonic cine may be in this large procedures COVID-19 vaccine pro population,safe or effective many the of vacwhom It looks like they’re as BY AMY KARON duced by Pfizer and Bio- are at high risk for serious safe as vitamin K MDedge News NTech. Close behind was antagonists. • 22 diverticular stricture or - the vaccine developed of a two- by See Vaccines · page 19 new clinical practice toryfistula, bowel ischemic disease, , Moderna. COVID-19 complications. update from the , and, inflammaof the Uni- AGAThe efficacy Clinical Practice Update A - Anne F. Peery, MD, MSCR American Gastro - wroteversity in of North Carolina, How diet and exercise can help terologistsenterological with Association practical Chapel“In our Hill, practice, and associates patients seeks to provide gastroen are reassuredGastroenterology. to know that manage NAFLD for management of colonic ongoing symptoms are com- and evidence-based advice mon and often attributable BY AMY KARON tients with nonalcoholic - For example, clinicians MDedge News - shoulddiverticulitis. consider lower en- - FLD), according to a clin- progression,”fat, which provides wrote aZobair poten tionto visceral is particularly hypersensitivity,” import- xercise and a hypo- icalfatty practice update (NA from tial for reversal of disease they wrote. “This conversa Ecaloric, Mediterra- - - doscopy and CT scans of If needed, ongoing abdomi- nean-style diet remain M. Younossi, MD, MPH, of contrastthe abdomen to rule and out pelvis chronic nalant painafter cana negative be treated workup. with the“[W]eight American loss Gastroenter is associat- Inova Fairfax Medical Cam with oral and intravenous See Diverticulitis · page 5 - ological Association. pusSee in Falls Diet, Church, exercise Va., · page 6 first-line interventions with his associates. diverticular inflammation, that can benefit all pa ed with a reduction in liver

At Digestive Disease Week® (DDW) 2021, now a fully virtual event, Centered you’ll explore today’s most pressing topics and exciting new on developments with leaders from around the globe in ,

Collaboration , endoscopy and gastrointestinal surgery.

Rosemont, IL 60018 IL Rosemont,

Suite 280 Suite

10255 W Higgins Road, Higgins W 10255 REGISTER ONLINE AT WWW.DDW.ORG/REGISTRATION.

PERMIT 500 PERMIT

CHANGE SERVICE REQUESTED SERVICE CHANGE HARRISBURG PA HARRISBURG

PAID

U.S. POSTAGE U.S. GI & Hepatology News Hepatology & GI

PRSRT STD PRSRT May 21-23, 2021 | VIRTUAL

01_4 thru 9_19_20_GIHEP21_2.indd 1 1/22/2021 4:20:06 PM †NEWS LETTER FROM THE EDITOR Finding common purpose, or else

am composing this editorial 4 days after (Am J Gastroenterol. 2020 Jun;115[6]:916-23), the U.S. Capitol was invaded and 10 days among others, emphasized that mild GI symp- ews Ibefore the presidential inauguration. It is toms may be the only presenting complaint for N

impossible to ignore what is happening in our people with COVID-19. Responses to COVID-19, eDge

country, but I hesitate to add my thoughts to such as limits on elective procedures and social MD the overwhelming sea of opinions circulating distancing, have upended our endoscopic pro- in standard media, social media, and the dark cesses and even altered the business models of that infant mortality among African American web. I hope, as do many, that we return to a GI practice. We will never go back to pre-COVID women is 2.3 times that of non-Hispanic Whites models. (https://minorityhealth.hhs.gov/omh/browse. I hope, as do many, The front page of this month’s GI & Hepatol- aspx?lvl=4&lvlid=23). Late effects of redlining that we return to ogy News features important articles for our continue to cause economic, health, and emo- practice. One article delves into an extensive tional harms (Badger E. “How Redlining’s Rac- a civil discourse, guideline from the American Gastroenterological ist Effects Lasted for Decades.” The New York recognize the Association on medical management of colonic Times. 2017 Aug 24). diverticulitis. In another article, they also de- “If Men were angels, no government would be voices of all scribe how efforts to encourage our patients necessary,” James Madison wrote. “In framing a people, respect with nonalcoholic to exercise government which is to be administered by men each other, and and manage their diet can make a real difference in their health. Finally, another explores how return to a belief in and why your immunocompromised patients governed;over men, theand great the next difficulty place, liesoblige in this:it to youcontrol science and facts. - itself.”must first enable the government to control the Dr. Allen ease) should and can be safely vaccinated for John I. Allen, MD, MBA, AGAF COVID-19(including .those with inflammatory bowel dis Editor in Chief civil discourse, recognize the voices of all peo- Meanwhile, we need civility, science, and com- ple, respect each other, and return to a belief in munity. Without common purpose, we will expe- science and facts. rience the William Forster Lloyd’s Tragedy of the Correction SARS-CoV-2 has devastated the world and Commons. Incivility has economic and emotional will continue to cause preventable deaths until costs, according to the Harvard Business Review The perspective for “Bariatric surgery re- we adopt stricter mitigation measures, vac- (Porath C and Pearson C. “The Price of Incivility.” solved NASH long term” that ran on pages cinate most people, and develop widespread 2013 Feb). “Weathering,” the deterioration of 4-5 of the October 2020 issue should read immunity. We are gaining immense knowledge Black women’s health over time that’s related “ regressed to F3 in two out of about this virus, and as gastroenterologists, we to continued socioeconomic disadvantage, has three patients” instead of “in two-thirds are on the front lines in many aspects. A recent multigenerational impacts; for example the De- of patients.” article in American Journal of Gastroenterology partment of Health & Human Services reports

mdedge.com/gihepnews

Editor in ChiEf, Gi & hEpatoloGy nEws Gi & hEpatoloGy nEws is the official newspaper of the American frontlinE mEdiCal CommuniCations John I. Allen, MD, MBA, AGAF Gastroenterological Association (AGA) Institute and provides the gastroenterologist soCiEty partnErs Editor in ChiEf, thE nEw GastroEntEroloGist with timely and relevant news and commentary about clinical developments Executive Editor Kathy Scarbeck, MA Vijaya L. Rao, MD and about the impact of health care policy. Content for Gi & hEpatoloGy nEws Editor Christopher Palmer assoCiatE Editors is developed through a partnership of the newspaper’s medical board of editors Megan A. Adams, MD, JD, MSc (Editor in Chief and Associate Editors), Frontline Medical Communications Inc. Creative Director Louise A. Koenig Ziad Gellad, MD, MPH, AGAF and the AGA Institute Staff. “News from the AGA” is provided exclusively by the Director, Production/Manufacturing Kim L. Isaacs, MD, PhD, AGAF AGA, AGA Institute, and AGA Research Foundation. All content is reviewed by the Rebecca Slebodnik Charles J. Kahi, MD, MS, AGAF medical board of editors for accuracy, timeliness, and pertinence. To add clarity and National Account Manager Joshua Norton Gyanprakash A. Ketwaroo, MD, MSc context to important developments in the field, select content is reviewed by and 512-375-8202, [email protected] Larry R. Kosinski, MD, MBA, AGAF commented on by external experts selected by the board of editors. Sonia S. Kupfer, MD Senior Director of Classified Sales Tim LaPella, The ideas and opinions expressed in Gi & hEpatoloGy nEws do not necessarily Wajahat Mehal, MD, PhD 484-921-5001, [email protected] reflect those of the AGA Institute or the Publisher. The AGA Institute and Frontline Editors EmEritus, Gi & hEpatoloGy nEws Medical Communications Inc. will not assume responsibility for damages, loss, Advertising Offices 7 Century Drive, Suite 302, Colin W. Howden, MD, AGAF or claims of any kind arising from or related to the information contained in Parsippany, NJ 07054-4609 973-206-3434 Charles J. Lightdale, MD, AGAF this publication, including any claims related to the products, drugs, or services Editorial Offices 2275 Research Blvd, Suite 400, Editor EmEritus, thE nEw GastroEntEroloGist mentioned herein. Advertisements do not constitute endorsement of products on Rockville, MD 20850, 240-221-2400 Bryson Katona, MD, PhD the part of the AGA Institute or Frontline Medical Communications Inc. aGa institutE staff POSTMASTER Send changes of address (with old mailing label) to GI & Managing Editor, GI & HepatoloGy News, Jillian L. Schweitzer Hepatology News, Subscription Service, 10255 W Higgins Road, Suite 280, FRONTLINE Managing Editor, tHe New GastroeNteroloGIst, Ryan A. Farrell Rosemont, IL 60018-9914. MEDICAL COMMUNICATIONS Senior Publications Manager, Brook A. Simpson RECIPIENT To change your address, contact Subscription Services at 1-800-430- Corporate Director of Publications Lindsey M. Brounstein 5450. For paid subscriptions, single issue purchases, and missing issue claims, call VP, Sales Mike Guire Vice President of Publications Erin C. Landis Customer Service at 1-833-836-2705 or e-mail [email protected] VP, Member Marketing & Digital Production Amy Pfeiffer offiCErs of thE aGa institutE The AGA Institute headquarters is located at 4930 Del Ray Avenue, Bethesda, MD President M. Bishr Omary, MD, PhD, AGAF 20814, [email protected]. President, Custom Solutions JoAnn Wahl President-Elect John M. Inadomi, MD, AGAF Circulation Director Jared Sonners Vice President John M. Carethers, MD, AGAF Gi & hEpatoloGy nEws (ISSN 1934-3450) is published Director, Custom Programs Patrick Finnegan Secretary/Treasurer Lawrence S. Kim, MD, AGAF monthly for $230.00 per year by Frontline Medical Scan this QR Code to visit Vice President, Proprietary Conferences, MedscapeLive ©2021 by the AGA Institute. All rights reserved. No part of this publication may be reproduced or transmitted Communications Inc., 7 Century Drive, Suite 302, mdedge.com/ David J. Small, MBA in any form or by any means, electronic or mechanical, including photocopy, recording, or any information Parsippany, NJ 07054-4609. Phone 973-206-3434 gihepnews storage and retrieval system, without permission in writing from the publisher. 2 February 2021 / GI & Hepatology News

02_GIHEP21_2.indd 2 1/21/2021 4:33:06 PM B:11.25" T:10.5" S:10" B:14.25 S:12.5 T:13 " " "

GIHEP_03.indd 1 12/14/2020 4:19:05 PM

SUTAB Product Spotlight Print Ad Size C Front_FINAL.indd 1 12/7/20 9:20 AM †FROM THE AGA JOURNALS Study reveals how aspirin may inhibit CRC

BY AMY KARON Wnt pathway, reduced stem cell (CRC) progresses, according to re- gene mutations, is fundamental to MDedge News expressionB: and7.875" function, and in- cancer initiation in both sporadic creased theT: 7.625"expression of Dickkopf “Dysregulated Wnt signaling, CRC and familial adenomatous spirin “rescued” a cystic intes- (DKK)-1, aS: Wnt 7.125" antagonist that is [whichcent study is] primarilyfindings. driven by ad- - Atinal phenotype driven by the frequently lost as enomatous polyposis coli (APC) tions reveal a novel mechanism of aspirin-mediatedpolyposis (FAP). ... Wnt Our inhibition observa through DKK-1 increase and po- tential ‘pheno-markers’ for chemo- prevention and adjuvant aspirin human trials,” wrote Karen Dunbar, PhD, and her associates in Cellular and Molecular Gastroenterology and Hepatology - . - ly Aspirinreduces shows CRC incidence, benefits inand sporad may delayic and disease familial progression adenoma, significant while

the biology responsible for this pro- tectiveimproving effect survival. is key to“Understanding developing biomarker-led approaches for ratio- nal clinical use,” wrote ,

Dr. Dunbar nowThey with found the aspirinUniversity promoted of Dundee (Scotland)the wild-type and (budding, colleagues. noncystic) phenotype in intestinal organoids

derived from APC-deficient mice and Withhumans the with RNAscope FAP. The protocol, same effect they was seen in live APC-deficient mice. B: 9.625" S: 8.875" reduced RNAT: 9.375" transcripts for Lgr5 and confirmed that aspirin significantly - TROY, which are stem cell markers inhuman CRC. Aspirinorganoids also derived reduced from Lgr5 nor- ex malpression colonic in APC-deficientmucosa, sporadic mice colo- and in rectal tumors, and colorectal tumors

In wound-closure models, aspi- rinfrom inhibited patients Wntwith andFAP. epithelial- mesenchymal transition (EMT) while decreasing migration and

Aspirin accomplished this by in- creasinginvasion theby colorectal phosphorylation cancer cells.of - bly, aspirin increased the produc- tionGSK-3beta of E-cadherin, and beta-catenin. which buffers Nota excess beta-catenin and thereby limits overactivated Wnt to pro- mote an epithelial, rather than

novel observation that the aspi- rin-mediatedmesenchymal, E-cadherin phenotype. increase “The is paralleled by greater E-cadher- in–beta-catenin binding further supports the hypothesis that aspi- rin promotes an epithelial pheno- type through Wnt inhibition,” the

In colorectal cells and FAP or- ganoids,researchers aspirin wrote. also increased the expression of the Wnt antagonist DKK-1, which in turn correlated Continued on following page

4 February 2021 / GI & Hepatology News

01_4 thru 9_19_20_GIHEP21_2.indd 4 1/21/2021 4:27:57 PM

SUTAB Product Spotlight Print Ad Size C Back_FINAL 2.indd 1 12/14/20 6:30 PM †FROM THE AGA JOURNALS AGA provides 14 recommendations

Diverticulitis from page 1

a low to modest dose of a tricyclic imaging if patients have had multi- reduces but does not eliminate the antidepressant.” ple recurrences, are not responding risk for recurrence. Quick Quiz The update from the AGA in- to treatment, are immunocompro- The authors recommended Q1. Which of the following cludes 13 other recommendations, mised, or are considering prophy- against surgery to prevent com- settings is associated with an with noteworthy advice to use lactic surgery. plicated diverticulitis in immuno- increase in the frequency of antibiotics selectively, rather than Colonoscopy is advised after ep- competent patients with a history transient lower esophageal routinely, in cases of acute uncom- isodes of complicated diverticulitis of uncomplicated episodes. “In this sphincter relaxations (TLESRs)? plicated diverticulitis in immuno- - population, complicated diverticu- A. Baclofen administration competent patients. In a recent cated diverticulitis if no high-quali- - - large meta-analysis, antibiotics tyor colonoscopyafter a first episode has been of performeduncompli tation of diverticulitis and is less tion did not shorten symptom duration in a year. This colonoscopy is ad- likelylitis is with most recurrences,” often the first the presen update C.B. Gastric Esophageal acid outflowhypersecretion obstruc or reduce rates of hospitalization, vised to rule out malignancy, which states. For acute complicated diver- D. Lean body mass complications, or surgery in this can be misdiagnosed as diverticuli- ticulitis that has been effectively E. Obstructive sleep apnea setting (Dis Colon . 2019 tis, and because diverticulitis (par- managed without surgery, patients Dec;62[12]:1533-47). The clinical ticularly complicated diverticulitis) are at heightened risk for recur- Q2. A 26-year-old female who practice update advises using anti- has been associated with colon rence, but “a growing literature is 7 weeks pregnant presents biotics if patients are frail or have cancer in some studies, the update suggest[s] a more conservative and with and vomiting. She comorbidities, vomiting or refrac- notes. Unless patients have “alarm personalized approach” rather than describes nausea that lasts most tory symptoms, a C-reactive protein symptoms” – that is, a change in the routine use of interval elective of the day with vomiting. She level above 140 mg/L, a baseline - resection, the authors noted. For all has tried rest and hydration, white blood cell count above 15 × mia, bloody stools, weight loss, patients, counseling regarding sur- ginger supplementation, and a 109 orstool abdominal caliber, iron-deficiency pain – colonoscopy ane gery should incorporate thoughtful wrist band she purchased over should be delayed until 6-8 weeks discussions of immune status, val- the counter. However, she comes CT scan. cells/L, Antibiotics or fluid collectionalso are strong- or a after the diverticulitis episode or ues and preferences, and operative to clinic to request further man- lylonger advised segment for immunocompromised of inflammation on until the acute symptoms resolve, - agement. patients, who are at greater risk whichever occurs later. fects on quality of life. The most appropriate next for complications. Because of this The decision to discuss elective risksDr. Peeryversus and benefits, another including author were ef step is: risk, clinicians should have “a low segmental resection should be supported by grants from the Na- A. Gastric-emptying study threshold” for cross-sectional imag- based on disease severity, not the tional Institutes of Health. The other B. Upper endoscopy ing, antibiotic treatment, and con- prior number of episodes. Although C. Ondansetron sultation with a colorectal surgeon. elective surgery for diverticulitis of interest. D. A diet high in carbohydrates, The authors recommend CT if has become increasingly common, authors reported [email protected] no conflicts low in protein patients have severe symptoms or patients should be aware that sur- E. Doxylamine with vitamin B6 have not previously been diagnosed gery often does not improve chron- SOURCE: Peery AF et al. Gastroenterol- (pyridoxine) with diverticulitis based on imag- ic gastrointestinal symptoms, such ogy. 2020 Dec 3. doi: 10.1053/j.gas- Answers on page 7 ing. Clinicians also should consider as abdominal pain, and that surgery tro.2020.09.059.

Continued from previous page with lower stem cell function. “In humans, high t is well known that aspirin protects against patients, Dunbar and colleagues performed serum DKK-1 correlates with increasing colorectal Icolorectal polyps and cancers, but the molec- - cancer stage, whereas tissue DKK-1 expression ular mechanisms by which aspirin confers this anisms by which aspirin acts to prevent the is lost with cancer progression,” the researchers protection remain obscure. By developing new developmenta comprehensive and studyprogression to define of CRC.the mech Here, explained. “Here, we demonstrate that aspirin ro- models and identifying the molecular targets Dunbar and colleagues found that aspirin bustly increases DKK-1 expression in CRC models, of aspirin, researchers may develop thera- limits cancer stem cell populations and the which contributes to EMT and [cancer stem cell] pies that prevent colorectal polyps development of EMT, which to- inhibition observed with aspirin.” and cancers but avoid the negative gether are important for tumor effects of aspirin. Most colorectal cell propagation, invasion, and dis- phenotypic indicators of aspirin response, the cys- cancers (CRC), both spontaneous semination. Importantly, they also tic-phenotypeTaken together, rescue the andfindings reduced “highlight stem celltwo marker novel and familial, arise from abnormal showed that aspirin increases the expression, which may serve as enhanced biomark- activation of an important molecular expression of a natural Wnt path- ers, compared with individual Wnt components,” pathway known as the Wnt-signal- way antagonist known as DKK-1, they concluded. “Through targeting Wnt signaling providing a mechanism by which at multiple levels, aspirin enhances commitment to a key member of this pathway, the aspirin inhibits Wnt signaling in differentiation, and hence, phenotypic markers of tumoring pathway. suppressor Specific APC, mutations are an early in the context of CRC. Future studies Wnt inhibition represent better targets [for] thera- event in spontaneous cancers and Dr. Katz can build on this work by exploring peutic exploitation.” are the cause of a condition known Dr. Dunbar and her associates reported having as familial adenomatous polyposis (FAP). Wnt approaches to Wnt inhibition and to prevent signaling also drives CRC by regulating cancer colorectalthese polyps findings and cancers. to develop targeted supported by Cancer Research UK and the Chief stem cells and a process known as epithelial- no relevant conflicts of interest. The work was mesenchymal transition (EMT). Jonathan P. Katz, MD, is an associate professor the CRUK. With use of established CRC cell lines, of medicine in the division of gastroenterology, Scientist Office of Scotland, the [email protected] Centre, and mouse models of FAP, and organoids – department of medicine at the University of three-dimensional models of colonic epi- Pennsylvania, Philadelphia. He has no conflicts SOURCE: Dunbar K et al. Cell Mol Gastroenterol Hepatol. thelium – from mice and from human FAP of interest. 2020 Sep 21. doi: 10.1016/j.jcmgh.2020.09.010.

MDedge.com/gihepnews / February 2021 5

01_4 thru 9_19_20_GIHEP21_2.indd 5 1/21/2021 4:28:05 PM †FROM THE AGA JOURNALS Bezafibrate eased pruritus in cholangiopathies

BY AMY KARON MDedge News tch really matters to patients frequently was associated with Iwith cholestatic liver diseases, nce-daily treatment with the hasdiarrhea. been implicated in cholangi- PPAR-agonist bezafibrate in a lipid-lowering agent bezaf- Lysophosphatidic acid (LPA) - mixed cholestatic population. O and effective treatment can make Clear benefitmeeting was the seen primary with dropathy-associatedainage rapidly improves pruritus severe but is exista significant for cholestatic difference itch to life qual around 50% of all disease groups patientsibrate with significantlycholestasis, accord-reduced itchnot foundin patients in bile. with However, primary biliary biliary ity. Although therapies moderate to severe pruritis among ramine, rifampin, and thereforeendpoint andthe answergood drug to and associates hypothesized that (such as cholesty- tolerance. Is bezafibrate - ing to the findings of a multicenter, cholangitis. Therefore, Dr. de Vries - - double-blind, randomized, placebo- naltrexone) recent data cholestatic itch? The cau controlled study (Fibrates for Itch, an as-yet-unknown factor in bile - from the United King tious answer is ... possi- or FITCH). - contributes to pruritus in fibrosing dom and United States bly, but more experience cipientsTwo weeks met the after primary completing endpoint, cholangiopathies and that bezafi suggest that therapy whichis needed. means The that trial long- du reportingtreatment, at 45% least of a bezafibrate 50% decrease re brate reduces itch by “alleviating atin leastpractice in part, is poor. from It is Dr. Jones ration was only 21 days, andhepatobiliary biliary secretion of this and biliary injury thelikely limitations that this results,of the and, thereby, reducing formation existing treatments term safety and efficacy in itch on a 10-point visual analogP = remain to be explored. - scale (VAS), compared with 11% of factor X.” ic itch withBezafibrate effects similar is now to being those patients in the placebo group ( - hospitalsThe FITCH in the study, Netherlands which was and which can be unpleasant to take used in practice to treat cholestat- .003). There was also a statistically conducted at seven academic (cholestyramine) or difficult to fore clearly an important new significant decrease in serum alka 18 years and older with primary use because of monitoring needs reported in the trial. It is there Pline phosphatase (ALP) levels from biliaryone in Spain,cholangitis enrolled or primary 74 patients or and side effects (rifampin and baseline (35% vs. 6%, respectively; secondary sclerosing cholangitis naltrexone). Itch has therefore option. Where it ultimately ends = .03) that corresponded with - been identified as an area of real up in the treatment pathway only improved pruritus, and bezafibrate an intensity of at least 5 on the unmet need in cholestatic disease,- Davidtime and Jones, experience BM, BCh, will PhD, tell. is a significantly improved both morn who reported having pruritus with and there are a number of trials in professor of liver immunology at withing and myalgia, evening rhabdomyolysis, pruritus. or progress or in set-up. This is ex Newcastle University, Newcastle Bezafibrate was not associated - 10-point VAS at baseline (with 10 tremely positive for patients. Upon Tyne, England. He reported indicating “worst itch possible”; cholestaticThe FITCH itch trial trials is one to reportof the having no disclosures relevant to serum alanine transaminase eleva median, 7; interquartile range, first of these “new generation” this commentary. tions but did lead to a 3% increase 7-8). Patients with hepatocellular in serum creatinine that “was not amongcholestasis most caused participants by medications ranged and explore the efficacy of the ofdifferent the department from the placeboof gastroenterol- group,” or pregnancy were excluded. Ages- - wrote Elsemieke de Vries, MD, PhD, from 30s to 50s, and approximate modest and similar between groups whose estimated glomerular filtra ogy & hepatology at Tytgat Institute treatmently two-thirds within were 10 female. days of None enroll- (3% with bezafibrate and 5% with tion rate was2 less than 60 mL/min gastroenterologyfor Liver and Intestinal & metabolism Research, at ment,had received and prior another treatment pruritus with be- placebo). Myalgia and increases in per 1.73 m , one such patient was Amsterdam, and of department of - serum alanine transaminase were accidentally enrolled. Her serum observed in BEZURSO but not in creatinine, measured in mmol/L, inAmsterdam Gastroenterology University Medical Cen zafibrate was not allowed. Patients FITCH. However, the short treatment rose from 121 at baseline to 148 on ters, and associates. Their report is received once-daily bezafibrate duration provides “no judgment on day 21, and then dropped to 134- . - (400 mg) or placebo tablets for 21 sclerosinglong-term safetycholangitis [of bezafibrate] or primary in tientafter donations,2 weeks off the treatment. Netherlands line-recommendedMost patients with treatments cholangitis days, with visits to the outpatient complex diseases such as primary The trial was supported by pa experience pruritus, but guide clinic on days 0, 21, and 35. tolerability, the investigators eventThere of wereoral pain no serious was considered adverse biliary cholangitis,” the investigators- investigatorsSociety of Gastroenterology, reported having and no can have sub par efficacy and- events or new safety signals. One mentwrote. – three stopped placebo be- Instituto de Salud Carlos III. The Four patients discontinued treat [email protected] wrote. For example, in a re - possibly related to bezafibrate, and - conflicts of interest. tivecent inhibitorstudy (Lancet. of an ileal2017 bile Mar acid itch and jaundice worsened in two cause of “unbearable pruritus,” and SOURCE: de Vries E et al. Gastroenter- 18;389[10074]:1114-23), a selec patients after completing treatment. one stopped bezafibrate after de ology. 2020 Oct 5. doi: 10.1053/j.gas- In the 24-month BEZURSO study veloping acute bacterial cholangitis tro.2020.10.001. transporter reduced pruritus in (N Engl J Med. 2018;378:2171-81), that required emergency treatment. primary biliary cholangitis but increases in serum creatinine were Although FITCH excluded patients Lifestyle changes can have a big impact on NAFLD Diet, exercise from page 1

-

Lifestyle modifications remain ,and surgery comorbid are usually diabetes, reserved or nonal- for typically requires a hypocaloric diet antioxidant, anti-inflammatory ef “the cornerstone for management” the subset of patients with severe of 1,200-1,500 kilocalories/day or a fects may slow NAFLD progression. worldwidebecause, even according though toNAFLD one meta-an- affects decrease of 500-1,000 kilocalories/- This diet minimizes or eliminates alyticapproximately assessment 25% of individuals wrotecoholic in Gastroenterology (NASH) with day from baseline. A Mediterranean sweets, refined grains, and red and at least stage 2 fibrosis, the experts diet of fresh vegetables, fruits, le processed meats. Fructose from as medications, bariatric (Hepatology. endoscopy, 2016 . gumes, minimally processed whole fruit is not associatedContinued on with following NAFLD, page Jul;64[1]:73-84), interventions such They note that achieving any sort grains, fish, olive oil, nuts, and but patients should consume little 6 of clinically significant weight loss seeds is recommended becauseFebruary its 2021 / GI & Hepatology News

01_4 thru 9_19_20_GIHEP21_2.indd 6 1/21/2021 4:28:14 PM Continued from previous page or no commercially prepared fruc- for cardiovascular disease and tose, which has been linked to vis- treatedconditions based should on guidelines be risk stratified from ceral adiposity, insulin resistance, the American College of Cardiology and the American Heart Associa- progression. Unfortunately other tion (J Am Coll Cardiol. 2019 Sep hypocalorichepatic inflammation, diets have andnot fibrosisbeen 10;74[10]:1376-414). Quick Quiz answers studied enough to support their It is believed that sarcopenia af- routine use in NAFLD treatment, fects patients with NASH cirrhosis Q1. Correct answer: E Q2. Correct answer: E according to the clinical practice because their livers cannot effec- Rationale Rationale update. tively store, metabolize, or mobilize Transient lower esophageal sphinc- This patient has nausea and vom- The recommndations also ad- carbohydrates, which leads to a ter relaxation (TLESR) is a phys- iting of pregnancy (NVP), and has dress patients with NASH, which catabolic state in which protein iologic phenomenon that allows tried conservative management.

is the more severe form of NAFLD and fat are used as energy sources, venting of swallowed air from the Doxylamine and vitamin B6 have according to the update. To avoid stomach in response to distension been found to be safe and effec- morbidity and mortality caused by exacerbations, these patients may of the proximal stomach. Patients tive for NVP and are considered complicationsand is associated from with cirrhosis, significant he- need to optimize their protein in- - patic decompensation, and hepato- take – a minimum of 1.2-1.5 g/kg with gastric-emptying study is not cellular carcinoma. It’s been shown of body weight is recommended throughwith gastroesophageal a compliant esophagogas- reflux dis necessaryfirst-line therapy. because Further NVP has testing a high that different degrees of weight – from sources of branched-chain tricease junction typically into reflux the gastric content prevalence at weeks 4-6 of ges- loss also has a big impact: Losing at during a TLESR; the frequency tation and peaks at week 9-16. A least 5% of total body weight can eggs, nuts, lentils, or soy. Patients of TLESRs may also be higher in nuclear test such as gastric emp- decrease hepatic steatosis, losing withamino sarcopenic acids, such NAFLD as chicken, also should fish, patients with GERD. TLESRs are tying is not appropriate during at least 7% can resolve NASH, and consume small, frequent meals suppressed during deep sleep, and pregnancy, though decreased losing at least 10% can lessen or spaced no more than 4-6 hours are less frequent when LES relax- gastric emptying due to estrogen - apart. When possible, they should ation is abnormal (e.g., esophageal and progesterone is thought to be ing to level 1 evidence cited by the consult with a specialized nutri- related to NVP. Upper endoscopy

stabilize hepatic fibrosis, accord- tionist. Moderate-intensity exercise GABAB receptor agonist, can reduce would be considered if the nausea cantly impact all aspects of NAFLD - outflowTLESR frequency, obstruction). and Baclofen, can reduce a - update. Weight loss “can signifi encing sarcopenia. - dansetron can be considered, but goal of 10% total body weight loss mayThe also researchers benefit patients disclosed experi ties thereand vomiting have been is refractory.some questions On shouldhistology be including considered fibrosis, for patients but a to Gilead Sciences, Intercept, Bris- obstructivereflux episodes sleep in apnea patients can with have re raised regarding safety and it is with overweight or obese NAFLD,” tol Myers Squibb, Novo Nordisk, increasedflux. Obese frequency patients and of TLESRs. those with The the authors wrote. Fat loss also and several other companies. The frequency of TLESR is not related to high in protein have been found to improves liver histology in patients review was commissioned and ap- degree of gastric acid secretion in decreasenot considered nausea first more line. that Meals carbo- with lean NAFLD (body mass index, proved by the AGA Institute’s Clini- the stomach. hydrate-rich meals. 26 kg/m2 in non-Asian patients or cal Practice Updates Committee and 24 in Asians), for whom a hypoca- the AGA Governing Board. References Reference loric diet targeting a more modest [email protected] Kuribayashi S et al. Neurogastroenterol Motil. 2010 Jun;22(6):611-e172. 3%-5% total body weight loss is ACOG Committee on Practice Bulletins-Obstetrics. Hershcovici T et al. Neurogastroenterol Motil. 2011 recommended. SOURCE: Younossi ZM et al. Gastroenter- Obstet Gynecol. 2018 Jan;131(1):e15-e30. Sep;23(9):819-30. Because aerobic exercise reduces ology. 2020 Dec 8. doi: 10.1053/j.gas- hepatic fat levels independently tro.2020.11.051. of hypocaloric diet, patients with NAFLD should consider a weekly regimen of 150-300 minutes of moderate-intensity exercise or 75- 150 minutes of vigorous activity. Resistance training can comple- ment aerobic exercise “but [is] not a replacement,” the authors noted. In addition, patients with NAFLD should restrict alcohol consumption to reduce the risk for liver-related Finding the right events, and those with advanced Job Alerts

- Gastroenterology Physician hol entirely.” These recommenda- San Francisco, California Full Time job or candidate is hepatic fibrosis should “avoid alco prospective study in which the Nurse Practitioner Washington, D.C. consumptiontions reflect the of evenfindings low of amounts a large Part Time at your fingertips of alcohol led to worse liver-re- Pediatric Gastroenterologist lated outcomes among patients Billings, Montana Full Time New Grad with NAFLD (Hepatology. 2020 Your career hub across all Mar;71[3]:835-48). Clinicians should screen for and disciplines and specialties in GI. “aggressively” manage common NAFLD comorbidities, including di- Start your search today at abetes mellitus, hypertension, and obstructive sleep apnea, according GICareerSearch.com. to the clinical practice update. Pa- COM19-024 tients with coexisting metabolic

MDedge.com/gihepnews / February 2021 7

01_4 thru 9_19_20_GIHEP21_2.indd 7 1/21/2021 4:28:21 PM †FROM THE AGA JOURNALS Normal FLIP findings usually ruled out esophageal motility disorders

BY AMY KARON MDedge News E ndoscopy is often the first step in the eval- Manometry revealed a major motility disorder uation of dysphagia and other esophageal in 23 patients with normal FLIP topography, Most patients with normal findings on symptoms such as chest pain. When endoscopy mainly because of esophagogastric junction functional luminal imaging probe (FLIP) is negative for a cause of these esoph- outflow obstruction (EGJOO) seen showed no clinical evidence of a major ageal symptoms and biopsies rule out in 20 patients, along with absent esophageal motor disorder, even when their eosinophilic , an esoph- contractility in 2, and distal esoph- high-resolution manometry (HRM) test results ageal motility disorder should be ageal spasm in 1. The EGJOO was were abnormal, according to the results of a sin- excluded, and high-resolution esoph- for the most part not confirmed by gle-center retrospective cohort study. ageal manometry is considered the adjunctive swallows on manometry Among 111 study participants with normal standard method for this purpose. or by esophagram, and aggressive FLIP findings, 79% also showed no evidence Functional lumen imaging probe therapies were not needed, indicating of a major esophageal motor disorder on (FLIP) panometry offers the oppor- Dr. Vela likely falsely positive EGJOO diag- esophageal HRM, wrote Alexandra J. Baumann, tunity to evaluate esophageal motor nosed by manometry. These are very DO, of Northwestern University, Chicago, and function during sedated endoscopy, encouraging results. If the findings Patientsassociates. with “Among normal the FLIPremaining panometry 21% with and it can be easily added to the en- are confirmed in larger prospective findings “did not have a clinical doscopic procedure if there are no findings to studies, it would be reasonable to consider explain esophageal symptoms. The prospect modifying our paradigm for the evaluation of impression of a major esophageal motor of establishing the presence of normal esoph- esophageal symptoms, and FLIP panometry disorder,” the researchers reported. ageal motility and ruling out a major motility could be considered as a screening tool to rule disorder during endoscopy is very attractive out a clinically significant major motility disor- because it would increase diagnostic efficiency ders during the initial endoscopic evaluation while also obviating the need for an additional Marcelofor esophageal F. Vela, symptoms.MD, MSCR, AGAF, is professor of apparent disagreement with HRM, [those] with and potentially uncomfortable study for the medicine, director of Esophageal Disorders, and normal FLIP panometry carried overall clinical patient. This study by Baumann and colleagues program director of Esophageal Fellowship in impressions of not having a major esophageal explores the yield of normal FLIP panometry the division of gastroenterology and hepatology motor disorder and subsequently were treated to predict the presence of normal esophageal at Mayo Clinic Arizona in Scottsdale. He reports conservatively without the need for surgical motility and rule out a major motility disorder. being a consultant for Medtronic and receiving interventions,” they reported. For patients with Their study showed that manometry was neg- research support from Diversatek. normal upper endoscopy and normal FLIP ative for a major motility disorder in 88 of 111 panometry, “the initial clinical management (79%) patients with normal FLIP panometry. strategy could be directed toward addressing gastroesophageal reflux or a functional syn- drome,” they wrote in Clinical Gastroenterology esophageal motor disorder,” the researchers re- the researchers wrote. Among 17 patients who and Hepatology. ported. In all, 23 (21%) patients with normal FLIP were available for clinical follow-up, 4 under- FLIP uses high-resolution impedance planim- results had discrepant (abnormal) HRM findings, went empiric dilation, of whom none had muco- etry to evaluate esophageal lumen parameters, most of which were false positives or equivocal. sal disruption. One patient was diagnosed with distensibility, and contractility in response For example, among 20 patients whose HRM dysphagia lusoria based on cross-sectional imag- to distension. Although HRM is standard for suggested an esophagogastric junction outflow ing, while the rest were managed conservatively. evaluating esophageal motility, false negatives obstruction, 17 showed normal bolus transit on Similarly, among 10 patients with at least 50% and positives can result from challenges with supine swallows and 16 showed normalization ineffective swallows on HRM, 5 showed normal interpreting outflow obstructions and normal of integrated relaxation pressure after adjunctive barium emptying and 9 were managed con- lower-esophageal sphincter relaxation pressures maneuvers. Similarly, among 10 patients who servatively (the remaining patient underwent among patients with clinical achalasia. Theunderwent strong acorrelation barium esophagram, between 8HRM showed and cricopharyngeal dilation for concurrent oro- Hence, the researchers evaluated correla- pharyngeal dysphagia). The strong correlation tions between FLIP and HRM in 111 patients esophagrams in this study indicates that between HRM and esophagrams in this study in- with esophageal symptoms and nonobstructive “[n]ormal findings from FLIP panometry can dicates that“[n]ormal findings from FLIP panom- endoscopy findings who were evaluated at the be used to exclude esophageal motility etry can be used to exclude esophageal motility Esophageal Center of Northwestern University disorders at the time of endoscopy, possibly re- between 2012 and 2019. Gastroenterologists disorders at the time of endoscopy, possibly ducing the need for high-resolution manometry performed additional studies, such as bari- reducing the need for high-resolution evaluation of some patients,” the investigators um esophagrams, at their discretion. By study concluded. “However, further longitudinal stud- design, all patients had normal FLIP results, manometry evaluation of some patients.” ies are needed to support this approach.” defined as an esophagogastric2 junction disten- The work was supported by the Public Health sibility index above 3.0 mm per mm Hg and a Service and the American College of Gastroen- normal contractile response (that is, normal re- terology. Dr. Baumann reported having no con- petitive retrograde contractions and a repetitive normal emptying, 1 showed a temporary delay flicts of interest. Four coinvestigators disclosed antegrade contraction pattern that met the Rule- but no retention, and 1 had an incomplete study. relevant ties to Crospon, Given Imaging, Iron- of-6s). Three clinicians evaluated and reached “The overall clinical impression was not of an wood, Medtronic, Sandhill Scientific,[email protected] Torax, and consensus on each FLIP study. Esophageal HRM achalasia variant in any of these 20 patients with other companies.. data were interpreted based on the Chicago clas- [esophagogastric junction outflow obstruction] SOURCE: Baumann AJ et al. Clin Gastroenterol Hepatol. sification system (version 3.0). on HRM, and thus none underwent botulinum 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.040. Patients with normal FLIP panometry findings toxin injection, pneumatic dilation, or lower-­ 8“did not have a clinical impression of a major esophageal sphincter myotomy at our center,” February 2021 / GI & Hepatology News

01_4 thru 9_19_20_GIHEP21_2.indd 8 1/22/2021 11:12:44 AM NEWS FROM THE AGA Estate plan: Misconceptions What are the risks from that can be costly surgery when removing hould your estate plan cause - colorectal polyps? you concern? Below are some dens and upset your estate plan. Scommon estate-planning mis- Toalso sidestep inflict unnecessary title traps, consult tax bur conceptions that can lead to prob- with an estate-planning attorney. urgery to remove colorec- lems down the road, plus ways to • “My will covers everything.” Not tal polyps is often unnec- avoid them. necessarily. Jointly owned assets Sessary according to recent • “I already have a will.” A will with rights of survivorship pass to research, which has found it can doesn’t improve with age. The pas- the surviving owner regardless of lead to adverse postoperative sage of time presents unanticipat- what your will says. Plus, your re- events and increased rates of

ed circumstances, such as changes tirement assets may never reach hospital readmissions. es g

in marital status, new children or your intended loved ones if you’ve To support GIs on how to best ma grandchildren, revised tax laws, - approach removal, the I etty

ignation forms. This could be true American Gastroenterological /G Revisit your will after major mile- forfailed assets to update such as beneficiary 401(k)s, IRAs, des Association has launched a new

stonesa move, or or at fluctuations least every incouple assets. of and life insurance policies, which on-demand course, “Appro- romaset years. pass outside of your will or trust priate Referral for Endoscopic • “Everything is joint.” Joint owner- - Polyp Removal.” The program second module of the program, ship seems ideal because it avoids plete new forms so old ones won’t guides you with three interactive learn about risk factors related probate and expedites the survi- leavevia beneficiary these assets designations. to a deceased Com modules and a decision-support to surgery. Other modules focus vor’s access. But joint title may parent or former spouse. tool on the best course of action on how to distinguish between • “I worry more about my heirs than with education on how to dif- lesions suitable for endoscopic myself.” A good estate plan should ferentiate between a simple and mucosal resection, lesions that complex polyp and when or if to should be referred for surgery, Ask an attorney who specializes refer patients for surgery. - inalso estate reflect planning your current about toolsneeds. Endoscopic resection of polyps section of tumors. Take the course that can provide you income for can eliminate the need for surgery and earnthe benefits 0.75 American of endoscopic Medical re life before supporting your family, more than 90% of the time. In friends, and favorite causes. fact, surgery almost doubles the on completion.

es risk of an adverse event. In the Associationwww.gastro.org/Polypectomy PRA Category 1 credit™ g

ma Want to learn more about including I a gift to the AGA Research Founda- etty

/G tion in your future plans? Visit our

uru website at https://gastro.planmy AGA Community Updates -G d

3 legacy.org.

scenarios regularly bring New research fellowship Physicianstheir questions with difficult to the AGA patient colleagues about therapy and dis- supports undergraduate easeCommunity management to seek options, advice frombest practices, and diagnoses. The up- graded networking platform now • Patient case: Unexplained jaun- minority students dice in an established cirrhotic patient scenarios and regularly (https://community.gastro.org/ - award provides a stipend, funding scheduledfeatures a newsfeedRoundtable for discussions difficult posts/23244) terological Association–Aman to offset travel and meal expenses, TArmaanhe new American Ahmed Family Gastroen and opportunities to learn about fu- In case you missed it, here are • Patient case: 76-year-old male Summer Undergraduate Research ture training and career options. somewith experts clinical in discussions the field. and with recurrent / persistent - Roundtables in the newsfeed this NET in proximal stomach promising students to pursue month: (https://community.gastro.org/ careersFellowship in science (SURF) encourages and medicine shareThis this is an opportunity incredible fellow with your posts/23243) while expanding the pipeline of networksship, and weand need your encourage help! any Pleaseeli- • investigators from diverse back- gible undergraduate students you patients (https://community. • Patient case: Entyvio and che- grounds. know to apply. gastro.org/posts/23449)COVID-19 vaccine and IBD motherapy (https://community. Six positions are available and We encourage students from all gastro.org/posts/23238) support undergraduate students in traditionally underrepresented • Simethicone use (https:// performing 10 weeks of digestive groups – members of racial and community.gastro.org/ • - disease–related research under ethnic minorities, individuals from posts/23448) ate sedation (https://community. the mentorship of an expert in disadvantaged backgrounds, or gastro.org/posts/23193)Discharge instructions for moder gastroenterology and hepatology. individuals with disabilities – to ap- • Students may select their own men- ply. The application deadline is Feb. getting it or not? (https:// View all discussions in the AGA tor or choose from a roster of more 24, 2021. community.gastro.org/COVID-19 vaccine – are you than a dozen AGA members. The www.gastro.org/surf posts/23442) gastro.org. Community at https://community. MDedge.com/gihepnews / February 2021 9

01_4 thru 9_19_20_GIHEP21_2.indd 9 1/21/2021 4:28:43 PM †PRACTICE MANAGEMENT How to predict colonoscopy malpractice lawsuits

BY JIM KLING were more likely to be ruled for the malpractice suits. Every year, about (13.4%), Pennsylvania (13.1%), MDedge News defendant, while those tied to med- 13% of gastroenterologists con- Massachusetts (12.5%), and New ication error favored the plaintiff, front malpractice allegations, and Jersey (7.9%). Gastroenterologists alpractice lawsuits related according to an analysis of cases colonoscopy is the most common were named in 71.1% of cases, in- to colonoscopy continue to from the Westlaw legal database. The reason. ternists in 25.6%, and surgeons in Mpose challenges for practi- study, led by Krishan S. Patel, MD, The researchers searched the 14.8%. tioners, and a new analysis reveals and Sushil Ahlawat, MD, MS, MBBS, Westlaw legal database for mal- A little more than half (51.8%) that errors related to sedation are AGAF, of Rutgers New Jersey Medical practice cases involving colonos- of cases were ruled in favor of the more likely to be awarded to plain- School, Newark, was published in the copy or sigmoidoscopy, identifying defendant, and 25% for the plain- tiffs. Primary care physicians and Journal of Clinical Gastroenterology . 305 cases between 1980 and 2017. tiff; 17% were settled, and 6% had surgeons are often codefendants, According to the authors, 55% of The average patient age was 54.9 a mixed outcome. Payouts ranged which emphasizes the importance physicians face a malpractice suit years, and 52.8% of cases were from $30,000 to $500,000,000, with of interdisciplinary care in colonos- at some point in their careers, and brought by female patients. The a median of $995,000. copy. gastroenterology ranks as the sixth most cases were from New York There were multiple causes Cases involving informed consent most common specialty named in (21.0%), followed by California Continued on following page

†LIVER DISEASE Updated USPSTF HBV screening recommendation may be a ‘lost opportunity’

BY JIM KLING or liver disease. Furthermore, a single-center MDedge News study found that, among physicians adminis- don’t think we have done a good job screening tering immunosuppressive therapy, a setting in thoseof people who infected are at risk,” with said HBV Dr. are Flores. aware of it. “I n update of the U.S. Preventive Services which HBV reactivation is a concern, there were Universal screening could help, but would ATask Force recommendation for low rates of screening for HBV infection, and have a low yield, according to Dr. Flores, who B screening shows little change from the 2014 the physicians did not reliably identify high-risk suggested expansion into other at-risk groups, version, but some wonder if it should have gone patients (PLoS One. 2015. doi: 10.1371/journal. such as Baby Boomers. With respect to other farther than a risk-based approach. pone.0120749). risk groups that could be stigmatized or discrim- The recommendation, which was published “This may also be viewed as a lost opportunity. inated against, Dr. Flores recalled her medical in JAMA, reinforces that screening should be Evidence suggests that risk factor–based screen- school days when some students went direct- conducted among adolescents and adults who ly into underserved communities. “We have are at increased risk of hepatitis B virus (HBV) conditions such as hepatitis B. Risk factor–based to think of creative ways of how to reach out infection. The USPSTF named six categories of ing is ineffective for the identification of chronic to people, not just relying on the usual physi- individuals at increased risk of infection: per- cian-patient relationship.” sons born in countries with a 2% or higher prev- screening is difficult to implement across health The World Health Organization has declared alence of hepatitis B, such as Asia, Africa, the “Risk factor–based screening is a target to reduce new hepatitis B infections by - difficult to implement across health 90% by 2030, and that will require addressing ca; unvaccinated individuals born in the United gaps in diagnosis. “We are at a critical juncture StatesPacific toIslands, parents and from some regions areas with of South a very Ameri high systems and exacerbates the burden on in terms of global hepatitis elimination efforts. - community-based organizations that are There is a time-sensitive need to have multistake- als; those who use injected drugs; men who have holder engagement in ensuring that all aspects sexprevalence with men; of HBVand people(≥8%); whoHIV-positive live with individu people motivated to address .“ of the care cascade are addressed. Because of who have HBV or who have HBV-infected sexual the central role of screening and diagnosis, it’s recommended that pregnant of critical importance that organizations such as women be screened for HBV infection during systems and exacerbates the burden on commu- USPSTF are in alignment with other organizations partners. It also nity-based organizations that are motivated to that have already issued clear guidance on who address viral hepatitis,” said Dr. Lim. importanttheir first prenatal document visit. because it validates the A similar view was expressed by Avegail examination of the evidence base will further importance“I view the of updated HBV screening, recommendations and the Grade as an B Flores, MD, medical director of liver transplanta- supportshould be broadening screened. ItUSPSTF is [my] guidance hope that to further include recommendation supports mandated insurance tion at the Michael E. DeBakey Veterans Affairs a larger group of at-risk individuals, or ideally a coverage for the screening test,” said Joseph Lim, Medical Center and assistant professor of medi- universal screening strategy,” said Dr. Lim. MD, AGAF, who is a professor of medicine at Yale cine at Baylor College of Medicine, both in Hous- The recommendation’s authors received travel University and director of the Yale Viral Hepati- ton. “This is a good launching point, and with reimbursement for their involvement, and one tis Program, both in New Haven, Conn. further evidence provided, hopefully it will also author reported receiving grants and personal Still, the recommendation could have gone fur- bring in a broader conversation about other per- fees from Healthwise. Dr. Flores has no relevant ther. Notably absent from the USPSTF document, sons who are at risk but not included in these yet featured in recommendations from the Cen- criteria.” Neither Dr. Lim nor Dr. Flores were in- American Association for the Study of Liver Dis- ters for Disease Control and Prevention and the volved in writing the guidelines. ease’sfinancial Viral disclosures. Hepatitis Dr.Elimination Lim is a member Task Force. of the American Association for the Study of Liver Dis- She noted that resistance to universal screen- [email protected] ease (Hepatology. 2018 Apr;67[4]:1560-99), are ing may be caused by the relatively low preva- patients who have diabetes, are on immunosup- lence of hepatitis B infection in the United States. SOURCE: U.S. Preventive Services Task Force. JAMA. 2020 pressive therapy, or have elevated liver enzymes However, the CDC estimates that only about 61% Dec 15. doi: 10.1001/jama.2020.22980.

10 February 2021 / GI & Hepatology News

10_11_GIHEP21_2.indd 10 1/21/2021 4:34:50 PM Continued from previous page “This isn’t a race. Clean the colon; make sure you you,” commented Dr. Kosinski. of litigation listed in 83.6% of No source of funding was dis- cases. Among these causes, the don’t miss something. If that person pops up in 3 years closed. Dr. Kosinski has no relevant most frequent were delayed treat- with a cancer, someone may go after you.” ment (65.9%), delayed diagnosis [email protected]\ (65.6%), procedural error/negli- to document the procedure thor- “This isn’t a race. Clean the colon; financial disclosures. gence (44.3%), and failure to refer/ oughly, including pictures of the ce- make sure you don’t miss something. SOURCE: Patel KS et al. J Clin Gastr. reorder tests (25.6%). If that person pops up in 3 years 2020 Dec 20. doi: 10.1097/ Of 135 cases alleging procedural don’t rush. with a cancer, someone may go after MCG.0000000000001471. negligence, 90 (67%) named perfo- cum and rectal retroflexion. Finally, ration. Among 79 cases that cited a failure to refer and order appropri- ate tests, 97% claimed the defen- dant missed a cancerous lesion. In cases alleging missed cancers, 31% were in the cecum, and 23% in the anus. A logistic regression anal- ysis of factors associated with a verdict for Dr. Kosinski the defendant Learn where you want found “lack of informed consent” to be an inde- pendent predictor of defendant verdict (odds ratio, 4.05; P = .004). “Medication error” was associated with reduced defendant success (OR, 0.17; P=.023). There were non-

odds of a verdict for the defendant Learn what you want andsignificant lawsuits trends that namedbetween “delay reduced in diagnosis” (OR, 0.35; P = .060) and “failure to refer” (OR, 0.51; P = .074). The authors sound a dire note about the number of malpractice suits brought against gastroenterol- ogists, but Lawrence Kosinski, MD, AGAF, is more sanguine. He notes that gastroenterologists have low Learn how you want insurance premiums, compared with other specialties, but recogniz- - cant source of risk. esDr. that Kosinski, colonoscopies who is arechief a medicalsignifi

a managing partner at the Illinois Gastroenterologyofficer at SonarMD Group, and formerly said in an interview that the study is reveal- DDSEP ing. “It comes out in the article: Acts Digestive Diseases Self-Education Program of omission are more dangerous to the physician than acts of commis-

acting on that malignant polyp, not pursuingsion. Not findingit, is much that more cancer, likely not to Customized by you get you in trouble than taking it off and perforating a colon,” said Dr. Whether preparing for a GI board exam or keeping current All at your fingertips. Kosinski, who was not involved in the study. on advances in the field, DDSEP 9 allows you to customize Also available on To gastroenterologists seeking to reduce their risks of litigation, learning where you want, what you want and how you want. AGA University and he offered advice: You shouldn’t Complete versions are available in digital and print formats ddsep.gastro.org assume that the patient has read the information provided. For ex- as well as by chapter, Q&A modules and/or mock exams. ample, risks of anesthesia and the

procedure itself should be directly EDU19-45 communicated. It’s also important

MDedge.com/gihepnews / February 2021 11

10_11_GIHEP21_2.indd 11 1/21/2021 4:34:55 PM †IN FOCUS: TUBE FEEDING Update on feeding tubes: Indications and troubleshooting of complications

BY GREGORY TOY, MD, AND The most general indication for JOHN C. FANG, MD nutrition support is an inability to maintain adequate nutritional Introduction needs with oral intake alone. Gen- Gastroenterologists are in a unique eral categories of inadequate oral position to manage individuals with intake include neurologic disorders, feeding tubes as their training un- malignancy, and gastrointestinal derscores principles in digestion, conditions affecting digestion and absorption, nutrition support, and absorption (Table 1). Absolute and enteral tube placement. Adequate relative contraindications to PEG management of individuals with placement are listed in Table 2. feeding tubes and, importantly, the If an endoscopic placement is not complications that arise from feed- possible, alternative means of ing tube use and placement require placement (i.e., surgery or inter- a basic understanding of intestinal ventional radiology) can be consid- anatomy and physiology. Therefore, ered to avoid the consequences of gastroenterologists are well suited to prolonged . In-hospital both place and manage individuals mortality following PEG placement Dr. Toy (left) is with the department of internal medicine at the University of with feeding tubes in the long term. has decreased 40% over the last Utah, Salt Lake City. Dr. Fang is with the division of gastroenterology and 10 years, which can be attributed hepatology at the University of Utah. Indications for tube feeding to improved patient selection, en- When deciding on the appropriate hanced discharge practices, and ex- - clusion of patients with the highest of patients with mild dementia to enteral tube placements. In individ- comorbidity and mortality rates, undergo gastrostomy increased in- uals with ICU-acquired weakness isroute enteral for artificialaccess versus nutrition parenteral sup like those with advanced dementia dependence fourfold; therefore, mul- and discharge to long-term care nutritionport, the firstsupport. decision Enteral to be nutrition made or terminal cancer.1 tidisciplinary involvement is often facilities, the placement of percu- necessary in the decision to pursue taneous endoscopic tubes may be preservation of the mucosal lining, required, although with the addi- reductionsconfers multiple in complicated benefits, including infections, When deciding on the in this population.4 tional consideration of the need for decreased costs, and improved pa- appropriate route, the artificialThe recent means coronavirus of nutrition disease support an aerosolizing procedure. Delay of tient compliance. All attempts at 2019 (COVID-19) pandemic has placement has been advocated, in adequate enteral access should be first decision to be made placed additional strains on endo- addition to appropriate personal made before deciding on the use of is enteral access versus scopic placement and has highlight- protective equipment, in order to parenteral nutrition. Following the ed the effect of the severe acute ensure safe placement for the en- parenteral nutrition support. respiratory syndrome coronavirus doscopy staff.6 means of nutrition support and 2 (SARS-CoV-2) on GI symptoms. enteralclinical decisionaccess, the to nextpursue common artificial de- A recent meta-analysis showed an Types of feeding tubes cision is the anticipated duration of PEG placement in patients with overall incidence of GI symptoms of After the decision to feed a patient nutrition support. Generally, the oral dementia is controversial, with pre- 17.6% in the following conditions enterally and determination of or nasal tubes are used for short du- vious studies not demonstrating in decreasing order of prevalence: the anticipated duration of enter- rations (i.e., less than 4 weeks) with improved outcomes and association anorexia, , nausea, vomit- al support, the next decision is to percutaneous placement into the with high mortality rates,2 so the ing, and abdominal discomfort.5 In determine the most appropriate stomach or for lon- practice is currently not recom- addition, the prolonged ventilatory location of feeding delivery: into the ger-term feeding (i.e., percutaneous mended by the American Geriatrics requirements among a subset of stomach or the small bowel. Gastric endoscopic gastrostomy [PEG] or Society in individuals with advanced individuals with the most severe feeding is advantageous most com- percutaneous endoscopic jejunosto- dementia.3 However, a large Japanese COVID-19 results in extended monly because of its increased ca- my [PEJ]). study showed that careful selection periods of nutrition support via pacity, allowing for larger volumes

ne of the most common con- perience with the placement and gastric or small-bowel delivery of Osultations gastroenterologists management of feeding tubes can feeds, and how to identify and man- receive is the request to place or be limited during training. age complications if they arise. This manage an enteral tube. A thor- The In Focus article for this quar- is an absolute must-read piece for ough understanding of indica- ter, which is brought to you by The any new gastroenterologist. tions for placement, type of tubes New Gastroenterologist, provides available, and the ability to trou- an in-depth review of feeding tubes Vijaya L. Rao, MD bleshoot common associated com- written by Dr. John Fang and Dr. Editor in Chief Gregory Toy (University of Utah). The New Gastroenterologist these requests and managing these This piece details the indications Dr. Rao is assistant professor of patientsplications appropriately. is imperative For in fielding the ear- for and contraindications to enteral medicine, University of Chicago, ly-career gastroenterologist, these tube placement, the variety of tubes section of gastroenterology, Dr. Rao calls can be daunting because ex- available, the decision between hepatology & nutrition.

12 February 2021 / GI & Hepatology News

12_13_14_GIHEP21_2.indd 12 1/21/2021 4:37:10 PM 149618a Headline for a Bar Graphic If a deck headline is needed, use this style.

Label style and size to be delivered over shorter du- Table 1. Indications for percutaneous placement have toInFocus become Print familiar Colors with the rations. However, in the setting of new syringes and feeding bags re-Axes number style and size postsurgical anatomy, gastropare- quired with EnFIT connectors. Note: Trade Gothic Medium, 8/11 ush left sis, or obstructing tumors/pancre- Neurologic Stroke, motor neuron disease (ALS), cerebral palsy, multiple sclerosis, Gastrostomy placement can be Source: Trade Gothic Medium, 8/11 ush left Parkinson’s disease, mild dementia considered a higher-risk endoscop- Oncologic Head and neck cancer, obstructing esophageal cancer, malignant tube feeds may be required into the ic procedure. One complicating Style Guide: atic inflammation, distal delivery of requiring gastric decompression . Additionally, percutaneous factor is the increased use of anti- Keep the background white. tubes placed into the stomach can Gastrointestinal Motility disorders, chronic , platelet and anticoagulant therapies Use the IMNG colors. have extenders into the small bowel in individuals with a history of Miscellaneous Polytrauma, coma, burns, cystic brosis, pulmonary/cardiac cachexia, Move the entire graph to align the bar labels left at the blue guide bar. (GJ tubes) to allow for feeding into prolonged critical illness neurologic insults. The American the small bowel and decompression Society for Gastrointestinal Endos-Headline (Resizing mayfor aneed Bar to Graphic be done on the graph to €t in the space.) 149618b If a deeper or shorter template is needed, adjust in Window > Artboards. or delivery of medications into the Source: Dr. Toy, Dr. Fang copy guidelines recommend that If a deck headline is needed, use this style. stomach. coumadin be held 5 days before the (Standard, as shown here, is 28 picas x 20 picas.) In general, gastric feeding is pre- procedure and bridged with hep- LabelTo create style and the size dotted lines if they change, use the clear arrow tool, click ferred over small-bowel feeding Table 2. Contraindications to PEG placement arin ifInFocus the patient Print is Colors at high risk of on the line that needs to be changed, use the eyedropper tool, then as PEG tubes are more stable and thromboembolic complications. ForAxes click number on thestyle dotted and size rule provided on the side of the template. Absolute Relative have fewer complications than patients on dual-antiplatelet thera-Note: Trade Gothic Medium, 8/11 ush left either PEG-J or direct PEJ tubes. Pharyngeal or esophageal obstruction py, thienopyridines like clopidogrel Abdominal wall abnormalities Source: Trade Gothic Medium, 8/11 ush left

Gastrostomy tubes are generally Signi cant coagulopathy Abdominal wall metastases are often stopped 5-7MDedge News days prior shorter and larger in diameter Inability to appose gastric and Open abdominal wounds to procedure with continuation of Style Guide: making them less likely to clog. aspirin,10 but there are more re- abdominal wall with transillumination Hepatomegaly/splenomegaly Keep the background white. PEG-J tubes have separate lumens cent data that PEG insertion is safe Use the IMNG colors. for gastric and small intestinal ac- and focal nger indention Ascites with continued use of DAPT.11 Di- Move the entire graph to align the bar labels left at the blue guide bar. cess, but the smaller-bore jejunal with rect-acting anticoagulants are often extension tubes are more likely to Prior gastric surgery stopped 24-48 hours prior to pro- (Resizing may need to be done on the graph to €t in the space.) clog or become dislodged. While cedure and then restarted 48 hoursIf a deeper or shorter template is needed, adjust in Window > Artboards. direct PEJ is shown to have higher Source: Dr. Toy, Dr. Fang after tube placement, but this is de- (Standard, as shown here, is 28 picas x 20 picas.) rates of tube patency and decreased pendent on the half-life of the spe-To create the dotted lines if they change, use the clear arrow tool, click rates of endoscopic re-intervention, need to be held for procedures or tube is chosen based on the size of on the line that needs to be changed, use the eyedropper tool, then compared with PEG-J,7 one limita- symptomatic gastric intolerance. the existing PEG tube and by mea- function. Patients with decreased click on the dotted rule provided on the side of the template. In clinical areas of question, or if suring the length of the stoma tract creatininecific DOAC clearanceand the patient’s may need renal to placement and site selection, which there is a concern for intolerance using specialized measuring devic- hold the DOAC up to 3-4 days prior

cantion beof performeda direct PEJ with is difficulty a pediatric in of enteral feeding, a short trial with es.8 Patients and caregivers can also to the procedure. In this situation,MDedge News colonoscope or balloon enteroscopy nasogastric or nasojejunal tube be trained to replace balloon-type referring to ASGE guidelines and placement should be performed be- tubes on their own to limit com- consultation with a hematologist or plications of displaced or cracked managing anticoagulation clinic is placement. - advised.10 After deciding to feed a patient foreWith a more respect definitive to percutaneous percutaneous mercially available for both gastric enterally, the next decision is to tubes, important characteristics placementtubes. Low-profile and gastric tubes placement are com Troubleshooting of to choose are the size (diameter with extension into the small bow- complications determine the most appropriate in French units), type of internal Nasoenteric tubes: One of the most location of feeding delivery. retention device, and external ap- for secure placement. common and irritating compli- pearance of the tube (standard or el,All which percutaneous often requires enteral fluoroscopy tubes cations with nasoenteric feeding tubes is clogging. To prevent clog- contain an external retention device connector system, which prevents 12 At system. Most commonly, this pro- low profile). All percutaneous tubes are being transitioned to the ENfit least 30 mL of free water should cedure is performed under general skin and an internal retention de- ging, flush the tube frequently. anesthesia. vice(i.e., thatbumper) is either that a fits balloon against or theplas- In the case of a critically hours for continuous feedings or In the case of a critically ill pa- tic dome or funnel that prevents ill patient in the ICU, it is beforebe used and to flushafter thebolus tube feeding. every Ad-4-8 tient in the ICU, it is recommended the tube from becoming dislodged. ditionally, 15-30 mL to start enteral nutrition within 48 Balloon retention tubes require re- recommended to start enteral of water should be given with each hours of arrival to avoid complica- placement every 3-6 months, while nutrition within 48 hours of separate medication administra- nonballoon tubes generally require tion, and if possible, medication Nasally inserted feeding tubes (e.g., replacement annually in order to arrival to avoid complications. administration via small-bore small Cortrak,tions of prolonged Avanos Medical calorie Devices, deficits. prevent the plastic from cracking, bowel feeding tubes should be Alpharetta, Ga.) are most common- which can make removal compli- avoided.12 - ly used at the bedside and can be connections from the enteral sys- cially important with small-caliber placed blindly using electromagnet- external cap, which, when opened, tem to nonenteral systems (namely, tubes and pumpsWater flushingthat deliver is espe both ic image guidance, radiographically, allowscated. Low-profile for extension tubes tubing have to anbe intravenous lines, chest tubes) and or endoscopy. However, the small securely attached while in use and vice versa. Tubing misconnections available for small-bowel feeding caliber of nasoenteric tubes comes detached while not in use. Low-pro- have been rarely reported, and infeeding order and to allow water for flushes. programmed It is with the common complication of the EnFIT system is designed to water delivery. clogging, which can be overcome among younger, active patients and prevent such misadventures that with slightly larger-bore gastric thosefile tubes with are adequate often preferred dexterity to have resulted in serious complica- unclog the tube,12 and additional feeding tubes. If gastric feeding is allow for attachment of the external tions and even mortality.9 Adapter pharmacologicWarm water flushesand mechanical can also help not tolerated (e.g., in the case of extension tubing. These tubes are devices are available that may be devices have been promoted for vomiting, witnessed aspiration), most often inserted as a replace- required for patients with feeding clogged tubes. One common tech- small-bowel feeding should be ini- ment for an initially endoscopically tubes who have not been transi- nique is mixing pancreatic enzymes tiated and can be a more durable placed tube, although one-step tioned yet. Most commonly with (Viokase) with a crushed 325-mg form of enteral feeding with fewer systems for initial placement are new tube placements and replace- tablet of nonenteric-coated sodi- interruptions as feedings do not ments, patients and providers will Continued on following page

MDedge.com/gihepnews / Februaryavailable. 2021 The size of the low-profile 13

12_13_14_GIHEP21_2.indd 13 1/21/2021 4:37:16 PM Continued from previous page seeding, peristomal leakage, and complication of PEG placement, al- tomy tube remain free of debris. um bicarbonate and 5 mL of water tube dislodgment. The prevalence though early reports have been de- Management is similar to that of to create a solution that has the of wound infection is 5%- 25%,16 scribed.18 The development of BBS unclogging nasoenteral tubes, as alkaline properties allowing for and randomized controlled trials occurs when the internal bumper - both pancreatic enzyme activation migrates from the gastric lumen mercial declogging devices for PEG and clog dissolution. Additionally, single dose of an IV antibiotic (i.e., through and into the stomach or discussedtubes include above, the andBionix specific Declog- com an endoscopic retrograde chol- cephalosporin)have demonstrated in those the efficacy not already of a abdominal wall. It occurs more ger® (Bionix Development, Toledo, angiopancreatography (ERCP) receiving a broad-spectrum anti- frequently with solid nonballoon Ohio) and the Bard® PEG cleaning catheter can be placed into longer biotic and administered prophy- retention tubes and is caused by brush (Bard Peripheral Vascular feeding tubes to directly infuse the lactically before tube placement.17 excessive compression of the ex- Tempe, Ariz.). The Bionix system activated agent to the site of the ternal bumper against the skin and has a plastic stem with a screw such that antibiotic administration abdominal wall. Patients with BBS and thread design that will remove beforeThe significance tube placement of this shouldreduction be is usually present with an immobile clogs in 14-24 French PEG tubes, More delayed complications considered a quality measure for catheter, resistance with feeds (be- the procedure. A small amount of cause of a closure of the stomach nylon stem with soft bristles at the of PEG insertion include redness around the tube site (less wall around the internal portion of endwhile to the prevent Bard mucosalbrush has injury a flexible and wound infection, buried than 5 mm) is typical, but extension the gastrostomy tube), abdominal can be used for prophylaxis against of erythema, warmth, tenderness, pain, or peristomal leakage. Physi- clogs, as well as removing clogs bumper syndrome, tumor purulent drainage, or systemic cians should be aware of and assess themselves.12 seeding, peristomal leakage, symptoms is consistent with in- tubes for BBS, in particular when Lastly, a rare but important com- and tube dislodgment. fection and warrants additional replacing an immobile tube (cannot plication of PEG placement is tumor antibiotic administration. Minor be pushed into the free stomach seeding of the PEG site in patients infections can be treated with local with active head and neck or up- antiseptics and oral antibiotics, and per gastrointestinal cancer.19 The clog.13 If water and enzymes are not early intervention is important to Thislumen) complication or when there can beis difficulty easily presumed mechanism is shearing successful in unclogging the tube, prevent need for hospital admis- preventedin flushing bywater allowing into the a minimum tube. of tumor cells as the PEG is pulled commercially available brushes can sion, systemic antibiotics, and even through the upper aerodigestive help remove clogs. The TubeClear® surgical debridement. between the external bumper and tract and through the wall of the system (Actuated Medical, Bellefon- Peristomal leakage is reported theof 0.5-1.0 abdominal cm (1 wall. finger In breadth)particular, stomach, as prior studies have te, Pa.) has a single-use stem that in approximately 1%-2% of pa- patients and caregivers should be demonstrated frequent seeding of is connected to AC power to create tients.18 Photographs of the site warned that if the patient gains tubes and incision sites as shown a jackhammerlike movement to can be very useful in evaluating by brushing the tube for malignant remove clogs in longer nasoenteral and managing peristomal leakage cells after tube placement.20 It is and gastrojejunal tubes. and infections. Interventions in- important to recognize this com- clude reducing gastric secretions Gastroenterologists plication and not misdiagnose it PEG tubes (short-term complications): with proton pump inhibitors and occupy a unique role in as granulation tissue, infection, or Procedural and immediate postpro- management of the skin with bar- evaluation, diagnosis, and bleeding as the spread of the cancer cedural complications include bleed- rier creams, such as zinc oxide generally portends a poor progno- ing, aspiration, , (Calmoseptine®) ointment. Place- management of patients sis. Therefore, it is best to use a PEG and perforation. Pneumoperitone- ment of a larger-diameter tube requiring enteral feeding. insertion technique that does not um occurs in approximately 50% enlarges the stoma track and only involve pulling or pushing the PEG of cases and is generally clinically worsens the leakage. In such cases, through the upper aerodigestive - thorough evaluations for delayed tract in patients with active cancer can be reduced by using gastric emptying (), and instead place tubes via an ex- 14 COinsignificant.2 The risk If the of patientpneumo distal obstruction, or constipation outer bumper will need to be loos- ternal approach by colleagues in in- develops systemic signs of infection should be performed and managed ened.significant Once amountsBBS is diagnosed, of weight, the the terventional radiology or via direct or peritoneal insufflation. signs, CT scan with accordingly. Opiates are common PEG tube requires removal and re- surgical placement. oral contrast is warranted for fur- contributors to constipation and placement as it can cause bleeding, ther evaluation and to assess for delayed gastric emptying and often infection, or fasciitis. The general Conclusion inadvertent perforation of overlying require reduction in use or direct- steps to replacement include endo- Gastroenterologists occupy a bowel or dislodged tube. Aspiration ed antagonist therapy to reduce scopic removal of the existing tube unique role in evaluation, diagno- during or following endoscopy is an- leaking. and replacement of new PEG in the sis, and management of patients other common complication of PEG Continuous feeding over bolus existing tract as long as the BBS is requiring enteral feeding. In ad- placement and risk factors include feedings and delivering nutrition not severe. In most cases a replace- dition, they are best equipped to over-sedation, supine positioning, distally into the small bowel (PEG-J ment tube can be pulled into place place, prevent, and manage com- advanced age, and neurologic dys- placement) can improve leaking using the pull-PEG technique at the plications of tube feeding. For this function. This risk can be mitigated from gastrostomy tubes. Addition- same gastrostomy site as long as reason, it is imperative that gas- by avoiding over-sedation, imme- al means of management include the stoma tract can be cannulated troenterologists familiarize them- diately aspirating gastric contents stabilizing the tube by replacing a with a wire after the existing tube selves with indications for enteral when the stomach is reached, and is removed. tubes and types of enteral tubes 15 In tube or using right-angle external Similar to nasoenteric tubes, PEG - addition, elevating the head of the bumpers.traditional If tube all measures with a low-profile fail, re- tubes can become clogged, although tion and management of common bedavoiding during excessive the procedure insufflation. and ded- moving the tube and allowing for this complication is infrequent. complications.available, as well Comprehensive as the identifica icating an assistant to perform oral stomal closure can be attempted,16 The primary steps for prevention understanding of these concepts suctioning during the entire proce- although this option often requires will augment the practicing gas- dure is recommended. parenteral nutrition support to water before and after feeds and troenterologist’s ability to manage prevent prolonged periods of inad- ensuringinclude adequately that all medications flushing with are patients requiring enteral nutrition PEG tubes (long-term complications): equate nutrition. liquid or well crushed and dis- More delayed complications of PEG Buried bumper syndrome (BBS) solved before instilling. Timely tube insertion include wound infection, occurs in 1.5%-8.8% of PEG replacement also ensures that the Seesupport references with confidence.at MDedge.com/ buried bumper syndrome, tumor placements and is a common late internal portions of the gastros- gihepnews/new-gastroenterologist.

14 February 2021 / GI & Hepatology News

12_13_14_GIHEP21_2.indd 14 1/21/2021 4:37:20 PM †GI ONCOLOGY CRC in young adults: Lower than previously reported Implications for screening recommendations tumors, which are frequently inci- - fact, many may be characterized as BY ROXANNE NELSON, RN, BSN screening is not recommended.” oscopy or colonoscopy. overdiagnosedhealth benefit from tumors, detection. which byIn The study authors explained that dentalThese findings carcinoid on tumorsflexible typicallysigmoid he risk for colorectal can- adenocarcinoma is a target for pre- are indolent, with a better progno- harms of screening without the bal- cer (CRC) in young adults is vention through screening because sis than most other cancer types, definition increase the burden and Tactually lower than has been it arises from precancerous polyps. the editorialists added. “Most likely, This new analysis showed that estimated, because previous stud- Those growths can be detected and the majority of carcinoid tumors 4%-20%ance of additional of the lesions benefit.” previously ies did not differentiate between removed before cancer develops. described as CRC were not adeno- colorectal adenocarcinoma and the That doesn’t apply to carcinoid Continued on following page histologically different carcinoid tu- identified by screening represent incidental findings with little say experts. mors,New which estimates are incidental for the risk findings, of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine (doi: 10.7326/ M20-0068). AGA Postgraduate They are important because this Course screening, say a trio of experts in anfinding accompanying has implications editorial. for CRC All new virtual experience Saturday, May 1, 2021 | 9 a.m.-4 p.m. Discover emerging science, leverage new tools and AGA Resource forge collaborations that will transform patient care. Help your patients understand colorectal cancer prevention New this year: and screening options by shar- ing AGA’s patient education Concurrent tracks allow you to from the GI Patient Center: customize your schedule www.gastro.org/CRC. Registration includes on-demand access and CME credits for one year

Reports of an increase in the in- Learn more and register at pgcourse.gastro.org. EDU20-093 cidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more re- cently in preliminary recommen- dations from the U.S. Preventive Services Task Force. However, that 2018 ACS recom- mendation to lower the starting age to 45 years was based to a Biosimilars large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the in IBD Care SEER (Surveillance, Epidemiology, Patients with IBD face many stresses. Using biosimilar and End Results) database (CA Can- cer J Clin. 2017;67:177-93). therapies shouldn’t be one of them. Learn: But that SEER-based study con- sidered “colorectal cancer” as a How to explain biosimilars to patients - What they should know about how pology, the editorialists pointed out. biosimilars keep IBD in remission. homogeneousThe new study, group the definededitorialists by to said, uses that same SEER database How to address their concerns but has “disentangled colorectal and allay their fears. adenocarcinoma, the target for screening, from other histologic Learn more at gastro.org/BiosimilarsIBD CRC types, including neuroendo- EDU20-091 crine (carcinoid) tumors, for which

MDedge.com/gihepnews / February 2021 15

15_16_17_GIHEP21_2.indd 15 1/21/2021 4:39:23 PM Continued from previous page carcinoma but carcinoid tumors, the editorialists pointed out. those aged 40-49 and 50-54 years. The greatest 3-year average - annual incident rate changes in This figure rose even higher adenocarcinoma (2000-2002 vs. in the subgroup of findings per 2014-2016) for any age group or increasetaining to in the early-onset rectum, the CRC. colonic Here, subsite were for rectal-only cases segment with the largest reported in the 20-29 years group (+39%), - as well as rectal-only cases in those s morsup to rather34% of than lesions adenocarcinoma, (depending e aged 30-39 years (+39%), and ag m

theyon patient noted. age) were carcinoid tu I colon-only cases in the age 30-39 tty

The three editorialists – Michael e ingroup rectal-only (+20%). adenocarcinoma in in- G Bretthauer, MD, PhD, and Mette Ka- / There was also significant increase hy - p dividuals aged 50-54 years (+10%). lager, MD, PhD, both of the Univer hotogra A statistically significant increase in

sity of Oslo, and David Weinberg,- DMEP the annual percentage change for MD, MSc, AGAF, of Fox Chase Cancer adenocarcinomas was observed for Center, Philadelphia – call for ac all age groups, except for colon-only tion based on the new findings. cases in the 20- to 29-years group “The ACS’s 2018 estimate of Karlitz said in an interview that he at age 50. Many of these cancers (0.7%) and for both colorectal about 7,000 new CRC cases among and his colleagues firmly believe could be prevented or diagnosed at (0.2%) and colon-only cases (–0.1%)carci- persons aged 45-49 years in the that colorectal cancer screening an earlier stage with screening at noidin those tumor aged 50-54 years. United States (the justification for for average-risk patients should early-onsetage 45.” colorectal cancer by Even though the absolute screening) needs to be adjusted begin at age 45 and that their new “This is the first study to analyze - incidence rates were downwardThey conclude on the that basis “caution of the newis research, despite its clarification lower than for adenocarcinoma evidence,” the trio wrote. about carcinoid tumors, provides specific histologic subtype,” Dr. Kar in all age groups and subsites,- a - evidence for that. litz also pointed out. statistically significant increase warranted when promoting the “There are a number of other adenocarcinomas,“Although colorectal adenocar carcinoidscino- combined-sitewas observed incolor theectal 3-year carcinoid av benefits of CRC screening for per studies that support screening - are increasing at a faster rate than erage annual incidence rate of sons younger than 50 years.” at age 45 as well,” he said. “This - However, the senior author of tal[new] cancer finding case supports burden inthe patients pres peoplemas constitute in their the40s overwhelmingand are also tumors in all age groups from the new study, Jordan Karlitz, MD, inence their of a40s large that preclinical is ultimately colorec un- majority of colorectal cancers in - increases2000–2002 in andrectal 2014–2016. carcinoid tu-This of ContraryTulane University, to the editorialists, New Orleans, Dr. mors,increase the was authors largely note. the result of strongly disagreed. steadily increasing, which has im covered with screening initiation plications for beginning screening at age 45,” he said. The authors also highlighted colorectalAdenocarcinomas cancers in also patients make un- up the results in the 40- to 49-year - the “overwhelming majority” of age group “because of differing opinions on whether to begin aver der 50 overall and “are the main age-risk screening at age 45 or 50 - driving force behind the increased- talyears.” and colon adenocarcinoma are colorectal cancer burden we are They reported that rates of rec- seeing in young patients,” Dr. Kar litz added. - increasing “substantially,” wheth Furthermore, “modeling studies er measured by changes in 3-year on which the USPSTF screening rec average annual incidence rate or ommendations were based [which by annual percentage changes. - recommended starting at age 45] The change in average annual Centered were confined to adenocarcinoma, incidence rate of colon-only ade thus excluding carcinoids from nocarcinoma for persons aged 40- on Steepesttheir analysis,” changes he said. in 49 years was 13% (12.21-13.85 adenocarcinomas in per 100,000), and that of rectal Collaboration younger groups adenocarcinoma was 16% (7.50- At Digestive Disease Week® (DDW) 2021, now a fully virtual event, - 8.72 per 100,000). Corresponding you’ll explore today’s most pressing topics and exciting new annual percentage changes were developments with leaders from around the globe in gastroenterology, In their study, Dr. Karlitz and col - adenocarcinoma0.8% and 1.2%, respectively. incident rates hepatology, endoscopy and gastrointestinal surgery. leagues assessed the incidence “These significant increases in Register early to receive discounted prices for the most prestigious rates of early colorectal cancer, us- meeting in GI. ing SEER data from 2000 to 2016, - commented.add to the debate over earlier and stratifying the data by histo screening at age 45 years,” they logic subtype (primarily adenocar Calls for next steps REGISTER ONLINE AT WWW.DDW.ORG/REGISTRATION. cinoma and carcinoid tumors), age - group (20-29, 30-39, 40-49, and - 50-54 years), and subsite. - The editorialists emphasize re A total of 123,143 CRC cases were straint when promoting the ben identified in 119,624 patients be efits of colorectal screening for tweenThe absolutethe ages ofincidence 20 and 54 rates years in persons younger than 50 years. May 21-23 | VIRTUAL during that time period. They point out that the USPSTF released a provisionalContinued on update following of page its the younger age groups (20-29 CRC screening recommendations 16 and 30-39 years) were very lowFebruary vs. 2021 / GI & Hepatology News

15_16_17_GIHEP21_2.indd 16 1/21/2021 4:39:35 PM †GI ONCOLOGY PDAC: Tumor reduction after neoadjuvant therapy may predict postsurgical survival

BY JIM KLING sor of medicine at Baylor College of treated with neoadjuvant therapy P MDedge News Medicine, Houston. for validation. The researchers used recursive “This is some helpful infor- Pathology examination revealed positioningsurvival (31% to vs.identify 18%; the < optimal.001). n patients who undergo resection mation that you can relay to the that, in the treatment-naive group, threshold for tumor reduction, and of pancreatic ductal adenocarci- patient, saying that you have a sig- 71% of tumors were larger than found that a 47% or greater re- Inoma (PDAC) after neoadjuvant the size determined during EUS. In duction was associated with 67% therapy, reduction in tumor size tumor based on your initial EUS, 9% of cases there was no change in overall survival at 3 years and 47% between diagnosis and surgery is nificantand your decrease chance ofin 3-the to size 5-year of the size (EUS versus pathology T-stag- at 5 years, compared with 32% and associated with improved survival, survival is going to be a lot higher, 16% for those with smaller reduc- according to a new single-center, compared to somebody that didn’t tion or tumors that maintained or retrospective analysis. The re- have that tumor regression. Most “This is some helpful increased in size (P searchers compared tumor size of these patients will undergo an The researchers noted that, as measured by endoscopic ul- EUS anyway, and you’ll commonly information that you can relay although their study < is .001). large, it trasound (EUS) and found that a if not always measure the tumor to the patient, saying that you remains retrospective in design. An- threshold of 47% or greater reduc- size while you’re in there. Now you other limitation they cited was that tion in tumor size at resection was can apply this information that you have a significant decrease not all patients received the same associated with a doubling in the already have to give the patients in the size of the tumor based neoadjuvant therapy. Furthermore, 3-year survival rate. some additional information if on your initial EUS.” both EUS and pathologic evaluation The study, led by Rohit Das, MD, they do undergo surgery,” said Dr. can be subjective, and it can be dif- of the University of Pittsburgh Sealock, who was not involved in the research. “While additional studies are re- Previous efforts to prognosti- quired,ficult to incorporating correct for that. preoperative cate postsurgical survival focused P EUS and postoperative pathologic A threshold of 47% or greater on overall tumor burden using ofing MDCT Pearson showed correlation a weaker coefficient, cor- tumor size measurements into the reduction in tumor size at multidetector CT (MDCT), carbo- relation.0.586;

15_16_17_GIHEP21_2.indd 17 1/21/2021 4:39:40 PM †CORONAVIRUS UPDATE During pandemic, many gastroenterologists report low resilience, insomnia

BY WILL PASS A total of 153 gastroenterologists MDedge News from 32 states completed the ques- tionnaire, among whom the mean “As sleep deprivation lmost one-third of gastro- age and years in practice were 46 enterologists may have low years and 13 years, respectively. has been associated with Aresilient coping skills, a Almost one-quarter of respondents burnout and medical errors - were female (22.7%). even outside the settings nia, according to a national survey The survey found that anxiety conductedfinding linked between with clinical May and insom June and depression were uncommon, of a global pandemic, of 2020. with respective rates of 7.2% and efforts to mitigate sleep The study, which was designed to 8.5%. characterize the psychological and In contrast, 30.7% of gastroen- deprivation seem key.” emotional health of gastroenterolo- terologists reported low resilient gists during the COVID-19 pandemic, coping skills. demonstrates how a complex array - of factors drives poor psychological tal processes and behaviors that a - person“Resilience uses to is protect defined themselves as the ‘men es, such as coronavirus exposure from the potential negative effects risk,health, reported rather thanlead authorspecific Eric challeng D. of stressors,’” the investigators es

Shah, MD, MBA, of Dartmouth-Hitch- wrote. “Resilient coping skills allow g ma

cock Health in Lebanon, N.H., and individuals in stressful situations to I

colleagues. avoid negative psychological health etty

“The COVID-19 pandemic pos- consequences such as depression /G es unprecedented and unique and anxiety.”

challenges to gastroenterologists The study showed that low resil- demaerre eager to maintain clinical practice, ience was associated with clinical patients’ health, and their own insomnia (odds ratio, 3.80; 95% important psychological health out- physical/mental well-being,” the comes including depression or anx- over an even longer period of as- investigators wrote in Clinical Gas- which occurred in more than iety,” wrote Dr. Shah and colleagues. sessment,”same effects he would said. be magnified confidence interval, 1.16-12.46), Instead, the investigators pointed Dr. Barnes, who authored an to resilience. article last year concerning in- “[W]e found that singular personal challenges, “Physician leaders and other ad- terventions for burnout in young practice-related challenges, and perceived ministrators should consider strat- gastroenterologists, offered some egies to maintain resilient coping practical insight (Dig Dis Sci. 2019 COVID-19–related exposure risks (such as skills among their colleagues such Feb;64[2]:302-6). perception of PPE availability) had little as dedicated resilience training “As sleep deprivation has been as- association with important psychological health and self-care,” the investigators sociated with burnout and medical wrote. errors even outside the settings of a outcomes including depression or anxiety.” They suggested that multiple global pandemic [JAMA Netw Open. Dr. Shah stakeholders, including profes- 2020. doi: 10.1001/jamanetworko- sional societies and policy makers, pen.2020.28111], efforts to miti- troenterology and Hepatology. one-quarter of respondents (25.5%). will be needed to implement such gate sleep deprivation seem key,” To learn more, Dr. Shah and Insomnia was also associated programs, and others. Additional he said. “Given that resilience is a colleagues conducted a national with age greater than 60 years, interventions may include ensur- skill that can be both learned and cross-sectional survey of gastroen- isolation outside the home, and ing personal protective equipment improved, focused interventions by terologists in the United States. years in practice. After adjustment availability, developing better health care systems to ensure the Primary outcomes included for sex, age, and resilient coping, technology for telemedicine, and presence of resilient coping skills clinical insomnia (Insomnia Se- univariate analysis showed that supporting small practices that among gastroenterologists could verity Index-7), general anxiety insomnia was associated with be a critical way to reduce psycho- disorder (General Anxiety Disor- isolation, female sex, and smaller elective procedures, the investiga- logical stress, prevent burnout, and der-7), and psychological distress practice size (fewer than 15 at- torsface wrote.financial obstacles in canceling improve the overall well-being of (Patient Health Questionnaire-8). tending physicians). Edward L. Barnes, MD, MPH, of the health care providers.” The investigators developed ad- While most respondents (85%) University of North Carolina at Chap- Dr. Shah is supported by the AGA ditional domains to characterize reported moderate to high well-be- el Hill, said that the 30% prevalence Research Foundation’s 2019 AGA- perceived coronavirus exposure - rate for low resilient coping skills was Shire Research Scholar Award in risks, practice-related challenges, cantly more likely to report clinical Functional GI and Motility Disor- and personal challenges. Further ing,anxiety, those depression, who didn’t and were insomnia signifi Dr. Barnes went on to suggest ders. He and his fellow investiga- assessment determined whether (P < .001 for all). thethat “most the survey striking” results finding. may actually tors, as well as Dr. Barnes, reported resilient coping skills (Brief Resil- “[W]e found that singular per- underplay the current psychological ient Coping Scale) or well-being sonal challenges, practice-re- landscape in gastroenterology. [email protected] (Physician Well-Being Index) were lated challenges, and perceived “This study encompassed 2 of no conflicts of interest. associated with psychological COVID-19–related exposure risks the early months of the COVID-19 SOURCE: Shah ED et al. Clin Gastroenter- health outcomes among surveyed (such as perception of PPE avail- pandemic (May-June 2020), which ol Hepatol. 2020 Dec 2. doi: 10.1016/j. gastroenterologists. ability) had little association with makes one wonder whether these cgh.2020.11.043.

18 February 2021 / GI & Hepatology News

18_21_22_23_GIHEP21_2.indd 18 1/21/2021 4:41:52 PM †CORONAVIRUS UPDATE Experts discuss concerns

Vaccines from page 1

At a special session held during get every year.” the 2020 annual meeting of the Dr. Wang noted that he couldn’t American Society of Hematology, think of any contraindications un- Anthony S. less the immunosuppressed patients Fauci, MD, the have a history of severe allergic re- nation’s leading actions to prior vaccinations. “But I infectious dis- would even say patients with history ease expert, said of cancer, upon recommendation Principles that individuals of their oncologists, are likely to be with compro- suitable candidates for the vaccine,” mised immune he added. “I would say clinicians systems, wheth- should approach counseling the of GI for the er because of same way they chemotherapy Dr. Fauci counsel patients or a bone mar- - row transplant, should plan to be cine, and as far NP and PA vaccinated when the opportunity asfor I the know, flu vacthere arises. are no concerns In response to a question from for systemic ASH President Stephanie J. Lee, MD, drugs commonly On-Demand of the Fred Hutchinson Cancer Cen- used in derma- ter, Seattle, Dr. Fauci emphasized tology patients.” that, despite being excluded from However, Dr. Wang clinical trials, this population should guidance has get vaccinated. “I think we should not yet been issued from either recommend that they get vaccinat- the FDA or the Centers for Disease ed,” he said. “I Control and Prevention regarding mean, it is clear the use of the vaccine in immuno- that, if you are compromised individuals. Given the on immunosup- lack of data, the FDA has said that pressive agents, “it will be something that providers history tells us will need to consider on an indi- that you’re not vidual basis,” and that individuals going to have should consult with physicians to as robust a re- sponse as if you potential risks. Dr. Lee had an intact weighThe CDC’sthe potential Advisory benefits Committee and immune system on Immunization Practices has said that was not being compromised. that clinicians need more guidance But some degree of immunity is bet- on whether to use the vaccine in ter than no degree of immunity.” pregnant or breastfeeding women, That does seem to be the consen- the immunocompromised, or those sus among experts who spoke in who have a history of allergies. The interviews: that as long as these are CDC itself has not yet released its Expert guidance on GI care: not live attenuated vaccines, they formal guidance on vaccine use. - Become empowered with stronger compromised patient, other than COVID-19 vaccines hold no specific risk to an immuno Vaccines typically require years of diagnostic and therapeutic skills. that could be a contraindication. research and testing before reaching any“Patients, factors specificfamily members, to the individual the clinic, but this year research- Learn the latest techniques from GIs friends, and work contacts should ers embarked on a global effort to be encouraged to receive the vac- develop safe and effective corona- and APPs leading patient care teams. cine,” said William Stohl, MD, PhD, virus vaccines in record time. Both chief of the division of rheumatol- Enhance your value to your team ogy at the University of Southern vaccines have only a few months of and patients. California, Los Angeles. “Clinicians phasethe Pfizer/BioNTech 3 clinical trial data,and Moderna so much should advise patients to obtain the remains unknown about them, in- Earn 15.25 CME where you want and vaccine sooner rather than later.” cluding their duration of effect and Kevin C. Wang, MD, PhD, of the any long-term safety signals. In ad- when you want. department of dermatology at Stan- dition to excluding immunocompro- ford (Calif.) University, agreed. “I mised individuals, the clinical trials Purchase today at am 100% with Dr. Fauci. Everyone did not include children or pregnant should get the vaccine, even if it women, so data are lacking for sev- nppa.gastro.org. may not be as effective,” he said. “I eral population subgroups.

But these will not be the only EDU20-080 vaccines that we recommend folks Continued on following page would treat it exactly like the flu MDedge.com/gihepnews / February 2021 19

01_4 thru 9_19_20_GIHEP21_2.indd 19 1/21/2021 4:28:53 PM Continued from previous page include immunocompromised in- explained. vaccines available, as the pipeline AGA Resource dividuals and thus, we can only ex- “There may be is already becoming crowded. U.S. For the latest clinical guidance, trapolate from what we know from some concern clinical trial data from a vaccine education, research, and phy- other trials of different vaccines,” that steroids jointly being developed by Oxford- sician resources about corona- he explained. “We know from prior and cyclospo- AstraZeneca, could potentially be virus, visit the AGA COVID-19 vaccines studies that the immune rine would ready, along with a request for FDA Resource Center at www.gas- response following vaccination is reduce the effec- emergency use authorization, soon. tro.org/COVID. less robust in those who are immu- tiveness of vac- In addition, China and Russia nocompromised as compared to a cines, but there have released vaccines, and there healthy control population.” is no concern Dr. Feldman are currently 61 vaccines being Dr. Kaplan also pointed to recent that any of the investigated in clinical trials and at reports of allergic reactions that drugs would cause increased risk least 85 preclinical products under medical specialties; people living have been reported in healthy in- from nonlive vaccines.” active investigation. rheumaticwith inflammatory diseases or(rheumatoid autoimmune dividuals. “We don’t know whether He added that there is evidence The vaccine candidates are us- arthritis,conditions, axial such spondyloarthritis, as inflammatory side effects, like allergic reactions, that “patients on biologics who re- ing both conventional and novel may be different in unstudied popu- ceive nonlive vaccines do develop mechanisms of action to elicit (Crohn’s disease and ulcerative lations,” he said. “Thus, the medical antibody responses and are immu- an immune response in patients. lupus); inflammatory bowel disease- nized.” Conventional methods include at- prioritize clinical studies of safe- tenuated inactivated (killed) virus colitis); psoriasis; multiple scle tyand and scientific effectiveness community of COVID-19 should Further advice and recombinant viral protein vac- androsis; life-long organ transplant immunosuppression recipients; vaccines in immunocompromised With other vaccines, biologic med- cines to develop immunity. Novel attributablepatients undergoing to HIV infection. chemotherapy; populations.” icines are held for 2 weeks before approaches include replication-de- As the vaccines begin to roll out So, what does this mean for an in- and afterward, to get the best re- and become available, how should dividual with an immune-mediated vaccines that contain the viral clinicians advise their patients, some patients ficient,protein, adenovirus and mRNA-based vector–based vaccines, in the absence of any clinical trial disease or who is don’tsponse. want “But to - data? immunocompromised?inflammatory disease like Dr. Crohn’s Kaplan stop the medica- cines, that encode for a SARS-CoV-2 explained that it is a balance be- tion,” said rheu- spikesuch as protein. the Pfizer and Moderna vac Risk vs. benefit tween the potential harm of being matologist “The special vaccine concern for , AGAF, a infected with COVID-19 and the Smith, DO, from immunocompromised individuals is gastroenterologist and professor uncertainty of receiving a vaccine Brett- introduction of ofGilaad medicine Kaplan, at theMD, University MPH of in an understudied population. For rial Physicians a live virus,” Dr. Calgary (Alta.), noted that the in- those who are highly susceptible to GroupBlount andMemo East Stohl said. “Nei- dying from COVID-19, such as an Dr. Smith Tennessee Chil- - community has dealt with tremen- dren’s Hospital, dousflammatory anxiety bowel during disease the pandemic (IBD) who faces high exposure, such as Alcoa. “They are afraid that their vaccinesther the Modare live because many are immunocompro- aolder health adult care with worker, IBD, orthe someone potential symptoms will return.” ernaviruses, nor so Pfizer there mised because of the medications protection of the vaccine greatly As for counseling patients as to should be no they use to treat their disease. outweighs the uncertainty. whether they should receive this special contrain- “For example, many patients with “However, for individuals who vaccine, he explained that he typical- dication for such ly doesn’t try to sway patients one individuals.” Dr. Stohl example, young and able to work way or another until they are really Live vaccine whichIBD are are on also biologics used inlike other anti-TNF im- are at otherwise lower risk – for high risk. “When I counsel, it really should be avoided in immunocom- [tumor necrosis factor] therapies,- extra months for postmarketing depends on the individual situation. promised patients, and currently, eases such as rheumatoid arthritis,” surveillancefrom home – studies then waiting in immuno- a few And for this vaccine, we have to be live SARS-CoV-2 vaccines are being hemune-mediated said. “Understandably, inflammatory individu- dis compromised populations may be open to the fact that many people developed only in India and Turkey. a reasonable approach, as long as have already made up their mind.” It is not unusual for vaccine trials medications are concerned about these individuals are taking great There are a lot of questions re- to begin with cohorts that exclude theals withrisk ofIBD severe on immunosuppressive complications due care to avoid infection,” he said. garding the vaccine. One is the participants with various health to COVID-19.” short time frame of development. conditions, including those who Lingering concerns “Vaccines typically take 6-10 years are immunocompromised. These with the world, celebrated the , of to come on the market, and this one groups are generally then evaluated announcementThe entire IBD that community, multiple vac-along - is now available after a 3-month in phase 4 trials, or postmarket- cines are protective against SARS- ston-Salem,Steven R. Feldman, N.C., said MD, that PhD there are study,” Dr. Smith said. “Some have ing surveillance. While the precise CoV-2, he noted. “Vaccines offer noWake contraindications Forest Baptist Health, for psoriasis in Win already decided that it’s too new for number of immunosuppressed the potential to reduce the spread patients to receive the vaccine, re- them.” adults in the United States is not of COVID-19, allowing society to gardless of whether they are on im- The process is also new, and pa- known, the numbers are believed revert back to normalcy,” Dr. Kaplan munosuppressive treatment, even tients need to understand that it to be rising because of increased - doesn’t contain an active virus and life expectancy among immuno- ulations, including those who are “Fortunately, there’s a lot of good “you can’t catch coronavirus from it.” suppressed adults as a result of immunocompromised,said. “Moreover, for vulnerable vaccines pop of- datathough coming definitive out of data Italy are that lacking. pa- Dr. Smith also explained that, advances in treatment and new and fer the potential to directly protect tients with psoriasis on biologics do because the vaccine may be less wider indications for therapies that them from the morbidity and mor- not appear to be at increased risk effective in a person using biologic can affect the immune system. tality associated with COVID-19.” of getting COVID or of having worse therapies, there is currently no in- According to data from the That said, even though the news outcomes from COVID,” he said. formation available on repeat vac- 2013 National Health Interview of vaccines are extremely promis- Patients are going to ask about cination. “These are all unanswered Survey, an estimated 2.7% of U.S. ing, some cautions must be raised the vaccines, and when counseling questions,” he said. “If the antibod- adults are immunosuppressed regarding their use in immuno- them, clinicians should discuss ies wane in a short time, can we compromised populations, such the available data, the residual un- be revaccinated and in what time This population covers a broad certainty, and patients’ concerns frame? We just don’t know that yet.” array(JAMA. of 2016;316[23]:2547-8). health conditions and trials, to my knowledge, did not should be considered, Dr. Feldman [email protected] as persons with IBD. “The current 20 February 2021 / GI & Hepatology News

01_4 thru 9_19_20_GIHEP21_2.indd 20 1/21/2021 4:29:04 PM †IBD AND INTESTINAL DISORDERS IBD patients more likely to stick with vedolizumab

BY HEIDI SPLETE - MDedge News AGA Resource matched pair analysis; discontinua associated with more systemic side tion, compared with infliximab, was effects,” she explained. - not statistically significant. Help your patients better The study design does not allow Adults with inflammatory “Several reasons may account for understand their IBD treatment for comment on comparative ef bowel disease were more significant rates of discontinuation options by sharing AGA’s ficacy, “although the findings are likely to continue using reported for all biological treatments patient education, “Living with intriguing,” said Dr. Isaacs. “If the vedolizumab, compared with anti– in IBD,” the researchers noted. “These IBD,” in the AGA GI Patient discontinuations were caused by - tumor necrosis factor (TNF) drugs comprise differences in health care Center at www.gastro.org/IBD. lack of efficacy, the findings in this over 3 years, based on data from systems in the concerned countries, study may help in positioning bio a retrospective study of nearly- including differences in availability- logic therapy in the biologic-naive - 16,000 patients. of biologicals, access to reimbursed tinuation among four biologics used patients,” she said. - Patient persistence with pre drugs, or different patient care set for inflammatory bowel disease The study is “a ‘real-world’ exper scribed therapy is essential to tings,” they wrote. over a 3-year period after initiation- iment that suggests there is a dif managing chronic inflammatory The study findings were limited of therapy in patients who were ference between different biologic - bowel disease (IBD), but data on by several factors including the lack previous biologically naive. Rea therapies for inflammatory bowel the persistence of patients with - of data on specific IBD diagnoses, sons for discontinuation cannot be - disease,” said Dr. Isaacs. “More con treatments are limited, wrote Ulf - IBD severity, disease course, and - assessed with this data set,” she - trolled comparative efficacy trials Helwig, MD, of the Practice for In dose escalation, they noted. noted. “There are very few compar are needed that can look at reasons ternal Medicine, Oldenburg, Germa However, the study was strength ative trials with the different bio for drug discontinuation between- ny, and colleagues. “With the advent ened by the large sample size and logic therapies in IBD. This trial is different populations. To date, the of vedolizumab, physicians for the use of a real-world setting, they important because it compares the VARSITY trial comparing vedoli first time had the choice between said.Comparisons inform choices two distinct biologic mechanisms of zumab to adalimumab in ulcerative biologicals with different modes of- action and continuation of therapy colitis is the only published trial to action,” they wrote. in biologically naive patients,” she- do this,” she added. In a study published in the Jour “There are multiple biologic options said. - The study received no outside nal of Clinical Gastroenterology, for therapy of inflammatory bowel Dr. Isaacs said she was not sur funding. Lead author Dr. Helwig the researchers used a national disease, and response to therapy - prised by the study findings. “Dis disclosed lecture and consulting prescription database to identify tends to drop off over time in many continuation of anti-TNF therapy fees from AbbVie, Amgen, Biogen, 15,984 adults aged 18 years and patients for a variety of reasons in was more common, compared to Celltrion, Hexal, MSD, Ferring, Falk older who were treatment naive to cluding development of antibodies vedolizumab and golimumab. There Foundation, Takeda, Mundipharma, biologics and received prescriptions and escape from the mechanism of was no statistical difference in - Pfizer, Hospira, and Vifor Pharma. between July 2014 and March 2017. the action of the drug,” said Kim L. terms of therapy discontinuation Dr. Isaacs disclosed serving on the Treatment persistence was defined Isaacs, MD, AGAF, of the University with infliximab,” she said. “In gen Data and Safety [email protected] Board as continuous treatment time of at of North Carolina at Chapel Hill, in eral, vedolizumab is felt to be less for Janssen. least 90 days without prescription. an interview. - systemically immunosuppressant SOURCE: Helwig U et al. J Clin Gas- A total of 2,076 vedolizumab - “Intolerance or side effects of with targeting of white blood cell troenterol. 2021 Jan. doi: 10.1097/ patients were matched with 2,076 medication also may lead to discon- trafficking to the gut, whereas anti-­ MCG.0000000000001323. adalimumab patients; 716 vedol tinuation of therapy,” said Dr. Isaacs. TNF therapy is more systemically izumab patients were matched “This trial looks at therapy discon immunosuppressant and may be with 716 golimumab patients; and- 2,055 vedolizumab patients were matched with 2,055 infliximab pa tients. Within 3 years after the first prescription, the overall persistence Apply to be the next rates were 35.9% for vedolizumab,- 27.8% for adalimumab, 20.7% for golimumab, and 29.8% for inflix imab. - Editor-in-Chief In matched-pair analysis, 35.2% of vedolizumab patients were per AGA’s premier publications — Gastroenterology, Clinical sistent, compared with 28.9% of - Gastroenterology and Hepatology and GI & Hepatology News — adalimumab patients over a 3-year period; the difference was statisti are seeking new leadership! cally significant. In addition, 30.5%- of vedolizumab patients persisted,- Learn more and mdedge.com/gihepnews compared with 25.4% of golimum apply at gastro.org. September 2019 ab patients, also statistically signif- DAAs reduce Volume 13 / Number 9 I N mortality, cancer S I D E IBD AND INTESTINAL DISORDERS icant. A matched-pair comparison risk in HCV study AGA Clinical Practice Update Large study with significant results. Recommendations for switching between

maGes i BY ANDREW biologics and biosimilars D. BOWSER

etty MDedge News hepatitis in IBD. C • 21 between vedolizumab and inflix /G virus P (HCV) GI ONCOLOGY A group of internists is alleging that the board is monopolizing the irect-acting antivirals MOC market. infection treated at 1 of CRC diagnosis ompilation France ( C delayed or missed in Drisk of hepatocellular 32There hepatology were no centers signs ofin). significantly decrease - patients under 50 imab (35.7% vs. 30.2%) was not in persons with hepatitis NCT01953458 Class-action According to survey, suit carcinoma and mortality treatmentincreased withrisk ofDAAs, hepato pro- young patients were filed - cellular carcinoma during- often misdiagnosed. against C, according to results of ABIM futing earlier, single-center • 22 over the first prospective, lon viding more evidence re LIVER DISEASE MOC gitudinal study to evaluate Women with cirrhosis statistically significant ( = 0.119).- BY ALICIA GALLEGOS thethe infection. effect of the drugs on MDedge News reports that had suggested survive hospitalization complications related to an increased incidence - more often than men group of internists is tiff-physicians are asking a terbalanceearly after atreatment. recent Co- Studying reasons will - cut suing the American judge to find ABIM in viola Compared risk of hepatocellu- with no These findings also coun help treatment. treatment, DAA therapy • In addition, vedolizumab patients A tion of federal antitrust law - 23 PRACTICE and to bar the board from chrane review that could lar carcinoma by about MANAGEMENT Board of Internal- tioncontinuing its MOC process. not confirm or reject a po on behalf - one-third and all-cause Why Pharma can’t Medicine over its main The suit is filed of allas ainternists class ac tential benefit of drugs on tenance of certification mortality by about half -in long-term morbidity and lower prices (MOC) process, alleging patientsthe study, which includ Report from the Senate were significantly less likely to dis - and subspecialists required with chronic mortality. that the board is monopo ed about 10,000 adult Lancet, Finance Committee cations.by ABIM to purchase MOC- to Results of the study, lizing the MOC market. The plaintiffs See DAAs hearing. maintain their ABIM seekcertifi published in the · page 23 • The lawsuit, filed Dec. 6, Distinct 25 - features 2018, in Pennsylvania district damages and injunctive re PUB20-020 court, claims that ABIM is found prices for maintaining lief, plus lawsuit and attorney BY ANDREW in continue therapy, compared with charging inflated monopoly cer- D. BOWSER young-onset costs statementarising from ABIM’s MDedge News CRC - alleged antitrust violations. tification, that the organi oung-onset In a colorectal review that included more zation is forcing physicians , ABIM expressed disappointment Y than 36,000 patients. Conversely, those younger to purchase MOC, and that at the lawsuit and said the - CRC patients younger both adalimumab and golimumab ABIM is inducing employers cancer (CRC) has dis patients were less likely to organization will vigorously than 50 years of age were and others to require ABIM tinct clinical and molecular have BRAF V600 mutations - defend itself, adding that more likely to have distal- certification. The four plain See - features, compared with than were patients 50 years- doing so will “consumeABIM · page re 31 primary tumors, synchro disease diagnosed later- in Cancer.old and older, the investiga nous metastatic disease, - tors reported in the journal life, according to investi and microsatellite instabil patients, with hazard ratios of gators who conducted a ity (MSI) than were older VerySee young patients were

patients, investigators said. more likely Distinctto have · pagesignet- 22

KY Jct.

Lebanon 2019

Rosemont, IL 60018 IL Rosemont, 384 No.

Permit AGA

0.86 and 0.60, respectively, in the PAID Postgraduate

Suite 280 Suite

Postage U.S. 21

Register at reduced rates until April 3, 2019. CHANGE SERVICE REQUESTED SERVICE CHANGE

Standard Presorted MDedge.com/gihepnews / February 2021 Road, Higgins W 10255 Course May 18 & 19,

2019 / San Diego, GI & Hepatology News Hepatology & GI Register now at pgcourse.gastro.org California.

EDU9-14

18_21_22_23_GIHEP21_2.indd 21 1/21/2021 4:41:57 PM †ENDOSCOPY DOACs look safe in elective endoscopic procedures

BY JIM KLING when you resumed the anticoagu- events, both in the DOAC group. MDedge News lant,” said Robert Jay Sealock, MD, The researchers also examined bleeding. assistant professor of medicine at the timing of anticoagulant resump- clinicallyStill, the significant research leftgastrointestinal some ques- mong patients taking direct Baylor College of Medicine in Hous- tion. Overall, 59.2% of subjects tions unanswered. Most of the high- oral anticoagulants (DOACs), ton. Dr. Sealock was not involved in received bridging therapy, including risk procedures were hot (41.8%) Aelective endoscopy proce- the study. 85% of the VKA group and 16% or cold snare polypectomies dures carry a risk of bleeding and The researchers examined data (39.8%). There weren’t enough thromboembolic events similar to from 1,623 patients who under- data in the study to evaluate risk in that seen in those receiving vitamin went 1,874 endoscopic procedures. DOACs have several advantages patients undergoing other high-risk K antagonists (VKAs), according Among these patients, 62.7% were over VKAs, including more procedures such as balloon dilation to a multicenter, prospective ob- taking VKAs, and 37.3% were tak- predictable pharmacokinetic for strictures, endoscopic ultra- servational study conducted at 12 ing DOACs; 58.9% were men, and Spanish academic and community the mean age was 74.2 years. Over- profiles and fewer food and and sphincterotomy. “That’s one centers. all, 75.5% were on anticoagulant drug interactions, but they have groupsound thatwith we fine-needle still don’t aspiration, really have DOACs have several advantages enough data about, particularly over VKAs, including more predict- most common procedures were not been well studied in the those patients who are on DOACs,” colonoscopytherapy for atrial (68.3%) fibrillation. and esoph- The elective endoscopy setting. said Dr. Sealock. fewer food and drug interactions, agogastroduodenoscopy (27.3%). The study also found a high butable they pharmacokinetic have not been profiles well studied and Within 30 days, the risk of bleed- number of patients on bridging in the elective endoscopy setting. ing was similar between patients of the DOAC group (P < .001). This therapy. “It highlighted the fact that Some previous studies suggested was not associated with increased we probably use bridging therapy a lower risk with DOACs, but they interval, 4.8%-7.8%) and DOACs endoscopy-related bleeding in ei- too much in patients undergoing were retrospective or based on ad- (6.7%;taking VKAs95% CI,(6.2%; 4.9%-9%). 95% confidence This was ther the VKA (3.3% with bridging endoscopy,” said Dr. Sealock. He ministrative databases. true regardless of intervention and therapy vs. 6.4% without; P = .14) recommended using tools that gen- The new study, which was led by site. or the DOAC group (8.3% vs. 6.4%; erate recommendations. Enrique Rodríguez de Santiago of Clinically significant gastroin- P = .48). The study was funded by the Universidad de Alcalá (Spain) and testinal bleeding occurred in 6.4% A total of 747 patients under- Spanish Society of Gastrointesti- was published in Clinical Gastroen- of subjects (95% CI, 5.3-7.7%); went a high-risk procedure, 46.3% nal Endoscopy. The investigators terology and Hepatology. 2.7% of clinically significant gas- of patients resumed anticoagulant - “It certainly showed there was an trointestinal bleeding events were therapy within 24 hours of the pro- terest. Dr. Sealock reported having - intraprocedural, and 4.1% were cedure, and 46.2% between 24 and reportednothing to having disclose. no conflicts of in cant rate of bleeding for patients on delayed. The risk of bleeding for 48 hours. After inverse probability [email protected] anticoagulants,acceptable rate andof clinically the thing signifi I appre- high-risk procedures was 11.5% of treatment weighting adjustment, ciated the most was that there was (95% CI, 9.4-14%). The overall a delay in anticoagulant resumption SOURCE: de Santiago ER et al. Clin mortality was 1.4%, with two was not associated with a reduction Gastroenterol Hepatol. 2020 Dec 3. doi: in terms of bleeding depending on deaths related to thromboembolic in the frequency of postprocedural 10.1016/j.cgh.2020.11.037. no statistically significant difference FDA clears device to remove dead pancreatic tissue

BY MEGAN BROOKS The EndoRotor System is made up of a power organ system failure caused by massive collec- console, foot control, specimen trap, and single-­ tions of infected pancreatic necrotic tissue. he Food and Drug Administration has use catheter. The EndoRotor System should not be used for approved the EndoRotor System (In- The device is used to perform endoscopic patients with known or suspected pancreatic Tterscope) for removal of necrotic tissue necrosectomy. In this procedure, a stent is used cancer, and the device will carry a boxed warn- in patients with walled-off pancreatic necro- to create a portal between the stomach and the ing stating this. The FDA said it knows of one pa- sis (WOPN). necrotic cavity in the pancreas to accommodate tient who died from pancreatic cancer 3 months “This device has shown its potential to provide a standard endoscope through which the Endo­ after having necrotic pancreatic tissue removed a minimally invasive way to remove harmful ne- Rotor cuts and removes necrotized tissue. with the EndoRotor System. crotic pancreatic tissue in patients with walled- The FDA approved the EndoRotor System on the “This patient did not have a diagnosis of pan- off pancreatic necrosis,” Charles Viviano, MD, basis of a clinical trial involving 30 patients with creatic cancer prior to treatment, although the PhD, acting director, Reproductive, Gastro-Renal, WOPN who underwent a total of 63 direct endo- patient’s outcome is believed to be unrelated Urological, General Hospital Device and Human scopic necrosectomies with the EndoRotor System. to the device or procedure,” the FDA said. The - The effectiveness of the EndoRotor System was de- EndoRotor System should be used only after pa- diological Health, said in a statement. termined by how well it cleared pancreatic necrot- tients have undergone other procedures to drain Factors“Currently, Office, in FDA order Center to remove for Devices dead tissueand Ra ic tissue measured during CT with contrast before the WOPN. It is also not appropriate for patients from a patient’s necrotic pancreatic cavity, and after the procedure, endoscopy, or MRI 14-28 with walled-off necrosis who have a documented health care providers need to perform an inva- days after the last procedure. Results showed an pseudoaneurysm greater than 1 cm within the sive surgery or use other endoscopic tools not average 85% reduction in the amount of necrotic cavity or with intervening gastric varices or un- tissue, with half of the patients having 98.5% clear- avoidable blood vessels within the access tract. With [this] marketing authorization, patients ance of necrotic tissue, the FDA said. The EndoRotor System was approved under withspecifically walled-off indicated pancreatic to treat necrosis this condition. now have a Three patients suffered procedure-related se- the de novo premarket review pathway for new new treatment option,” said Dr. Viviano. rious adverse events (10% complication rate). low- to moderate-risk devices. WOPN is a potentially deadly condition that oc- Two patients experienced gastrointestinal bleed- curs in about 15% of patients with severe pancre- ing. One patient had a pneumoperitoneum and A version of this article first appeared on atitis. Often, the dead tissue must be removed. later died after suffering from sepsis and multi- Medscape.com.

22 February 2021 / GI & Hepatology News

18_21_22_23_GIHEP21_2.indd 22 1/21/2021 4:42:02 PM †ENDOSCOPY AGA white paper highlights interventional endoscopic ultrasound

BY WILL PASS niques, however, has been mixed. such as the esophagus, liver, and complications, recovery time, and MDedge News While LAMS “have gained pop- pancreas, EUS would appear to be nondiagnostic yield). And biopsies ularity in the management of an ideal tool to provide imaging and - espite the surgery-sparing pseudocysts and walled-off necrotic potentially ablation of benign and ed liver procedures to come, the potential demonstrated by - mayinvestigators be the first suggested. of many EUS-guid Dinterventional endoscopic ority over plastic stents have been wrote Dr. Hwang and colleagues. “[EUS-guided liver biopsy] likely ultrasound (I-EUS), widespread collections,” data regarding superi malignantBut several lesions challenges in these may locations,” stand will be followed by EUS-guided por- clinical adoption will require more risk of bleeding in necrotic cavities, - tal pressure gradient measurement prospective trials, formalized train- wroteconflicting, Dr. Hwang and LAMS and colleagues.may increase doscope length and working channel and EUS-guided shear wave elas- ing programs, and greater support “Placement of coaxial plastic caliber,in the way, “the including tortuosity insufficient of the gas- en from key stakeholders, according stents through the lumen of LAMS “There now is potential for a one- to an American Gastroenterological has been advocated to try to mini- relative to some parts of the liver stop-shoptography,” diagnosisthe investigators and staging wrote. of Association white paper. mize the risk of complications relat- trointestinaland pancreas, lumen” prohibitive and its tumor location The publication, which was con- characteristics, and cost. In addition, Still, work is needed to facilitate ceived during a session at the 2019 EUS-guided pancreatic interven- concerns remain for collateral dam- greaterliver disease.” clinical adoption of inter- AGA Tech Summit, addresses the tionsed to remainLAMS,” theymost added. challenging; age to surrounding organs. ventional EUS. current status and future directions Both pancreaticogastrostomy and “Further studies evaluating the “[W]idespread implementation of I-EUS, included EUS-guided ac- EUS-guided pancreatic rendezvous safety and treatment response to of interventional EUS is likely to cess, EUS-guided tumor ablation, are associated with technical failure ablation of solid neoplasms is re- require support from gastrointesti- and endohepatology. rates up to 40%, and adverse event nal societies and buy-in from other “We hope this white paper guides rates may be as high as 35%. those interested in adoption of “Unlike other EUS-guided drain- EUS-guidedquired,” the investigators liver applications wrote. wrote Dr. Hwang and colleagues. these technologies into clinical age and access procedures, there According to Dr. Hwang and col- keyThe stakeholders white paper including resulted payors,”from a practice and serves as a foundation has been limited improvement in leagues, a growing body of evidence session focused on interventional for future research and innovation technology to make EUS-guided supports EUS-guided liver biopsy, EUS at the 2019 AGA Tech Summit, including a high rate of histologic organized by the AGA Center for in Clinical Gastroenterology and Dr. Hwang and colleagues con- diagnoses (93.9%), Doppler-based GI Innovation and Technology. The Hepatology.in the field,” the investigators wrote cludedpancreatic this accessdiscussion easier of orLAMS safer.” by investigators disclosed additional According to senior author Joo Ha calling for randomized prospective needle track prior to needle re- Hwang, MD, PhD, of Stanford (Calif.) trials. They also noted the expense moval,detection ability of blood to perform flow within several the Vyaire Medical, Cook Medical, and University, and colleagues, some of of LAMS, which may cost $4,000- needle actuations through a sin- others.relationships with Boston Scientific, the described techniques are not $6,000. gle puncture in the liver capsule, [email protected] new, but they have yet to be fully rapid patient recovery, ability to realized. EUS-guided tumor ablation sample both liver lobes, potential SOURCE: DeWitt JM et al. Clin Gastroenter- “Some of these techniques ini- “Because of the close proximity of for simultaneous endoscopy, and ol Hepatol. 2020 Sep 17. doi: 10.1016/j. tially were reported more than the to organs lower overall cost (accounting for cgh.2020.09.029.

wrote. “However, with further de- a decade ago,” the investigators in technique there is potential for expandingvice development the application and refinement of these techniques and new technologies to a broader group of interventional

gastroenterologists.”EUS-guided access “There has been exponential growth in EUS-guided biliary (in- cluding gallbladder) access and GI Forging drainage procedures, as well as entero-enteric anastomotic proce- - Forward tigators wrote. “This change can bedures attributed in recent to years,” the availability the inves of lumen-apposing metal stents Gain knowledge, insights and professional development across Previous studies have reported research, disaster/crisis management and guideline development. promising(LAMS).” success rates with LAMS across a variety of EUS-guided pro- Live and on-demand sessions are now available on AGA University cedures, including biliary drainage at agau.gastro.org. (equal to or greater than 85%), gallbladder drainage (90%-98%), and gastrojejunostomy (greater MEM20-043 than 90%). Success with other tech-

MDedge.com/gihepnews / February 2021 23

18_21_22_23_GIHEP21_2.indd 23 1/21/2021 4:42:06 PM B:11" T:10.5" S:10" S:12.5" B:13.5" T:13"

GIHEP_24.indd 1 1/11/2021 8:55:35 AM

PREPARED BY 11419682 US BMS DSA Journal Ad - KING M5FR Job info Images Fonts Special Instructions Date: 12-17-2020 3:07 PM BMS Brand Image.ai (54.36%; 1.1MB), BMS Humanity (Bold, Regular, Italic), BMS Create composite ad per specs + BMS instruc- Client: BRISTOL-MYERS SQUIBB BMS_A060059_4C.tif (CMYK; 370 ppi; 81.08%; Humanity Nw (Regular) tions (T/C). No KO type smaller than 6 pt.; Product: BMS-OZANIMOD GLOBAL-UC 53.2MB) standard SWOP specs; flatten transparencies. Client Code: IMM-US-2000044 Additional Information WF Issue # 7855809 None Releasing as: Native Files Final Size: None Finishing: None Gutter: None Inks Additional Comments for Sizing Colors: 4/C Cyan, Magenta, Yellow, Black None Team Producer: None AD: Sean Calandrillo; David Grillo AE: Nijah Dupiche Scale: 1" = 1" QC: None Bleed 11" w x 13.5" h 11"wx13.5"h Production: Debi Post 973-451-2208 / M +1 917-938-4356 Trim/Flat 10.5" w x 13" h 10.5"wx13"h Digital Artist: McAuliffe, Aly (PPY-FCR) Live/Safety 10" w x 12.5" h 10"wx12.5"h FR Spellcheck: None

Path: PrePress:BRISTOL-MYERS_SQ:BMS-OZANIMOD_GLOBAL-:11419682:11419682_US_BMS_DSA_Journal_Ad_KING_M5FR.indd _ _

Cosmos Communications 1 Q1 Q2 C M Y K ej 43901a 12.18.20 133 1