Incorporating Psych Care in Management of Chronic Digestive

VOL. 12 NO. 4 APRIL 2018

Incorporating psych INSIDE NEWS care in management Commentary Some AGA wins in Congressional of chronic digestive budget. • 5

FROM THE AGA

IEGEL diseases JOURNALS

A. S Opioids linked to BY CHHAVI JAIN of patients across the spec- OREY mortality in IBD . C Frontline Medical News trum of disease to brain-gut R Prescriptions for opioids D psychotherapies is crucial. sychogastroenterol- In a review by Laurie have increased in the

OURTESY past 20 years. • 9

C ogy is the science of Keefer, PhD and her co- Disease severity indexes were created for each severity attribute on Papplying psychological authors, published in the a 100-point scale, reported Dr. Corey A. Siegel. principles and techniques April issue of Gastroenter- IBD AND INTESTINAL to alleviate the burden of ology, provided a clinical DISORDERS chronic digestive diseases. update on the structure Tofacitinib approved New study establishes This burden includes diges- and efficacy of two major for UC tive symptoms and disease classes of psychogastro- FDA panel adds severity, as well as patients’ enterology – cognitive- indication. • 21 IBD severity index ability to cope with them. behavioral therapy (CBT) Chronic digestive diseases, and gut-directed hyp- BY MADHU RAJARAMAN ysis found that, in Crohn’s such as irritable bowel syn- notherapy (HYP). The ENDOSCOPY Frontline Medical News disease, mucosal lesions, drome, gastroesophageal review discussed the Nonendoscopic fistulas, and abscesses were reflux disease, and inflam- effects of these therapies nonmalignant polyp xperts have established the greatest contributors to matory bowel diseases, can- on GI symptoms and the surgery up a severity index for disease severity at 15.8%, not be disentangled from patients’ ability to im- This procedure is not Einflammatory bowel 10.9%, and 9.7%, respec- their psychosocial context. prove coping, resilience, recommended, disease (IBD), according tively. In ulcerative colitis, In this regard, the role of and self-regulation. The however. • 24 to results of an analysis 18.1% of disease severity gastroenterologists in pro- review also provided a published in the journal was attributed to mucosal moting best practices for framework to understand Gut (doi: 10.1136/gut- lesions, 14% to impact on the assessment and referral See Psych care · page 21 jnl-2016-312648). daily activities, and 11.2% The index, conceived by a to C-reactive protein, wrote panel of IBD specialists from Corey A. Siegel, MD, MS, of NASH rapidly overtaking hepatitis C the International Organiza- the Dartmouth-Hitchcock tion for the Study of Inflam- Medical Center in Lebanon, matory Bowel Diseases, is a N.H., and his coauthors. as cause of liver cancer step toward the standardiza- Investigators used a BY BIANCA NOGRADY cancer in the United States. Journal of Clinical and Ex- tion of disease severity defi- PubMed literature search to Frontline Medical News Researchers reported perimental Hepatology. nitions in ulcerative colitis identify three broad elements on their analysis of past The analysis, based on and Crohn’s disease. of disease severity: impact of onalcoholic steatohep- prevalence of HCV, NASH, data from the National The panel determined disease symptoms on daily Natitis (NASH) is rapidly and alcoholic cirrhosis and Health and Nutrition Ex- 16 severity attributes for activities, inflammatory bur- eclipsing hepatitis C virus prediction of future trends amination Survey and the Crohn’s disease and 13 for den, and disease course. (HCV) infection as the and their effect on hepato- Organ Procurement and ulcerative colitis. The anal- See Index · page 20 leading contributor to liver cellular carcinoma in the See NASH · page 22

2018 AGA Saturday, June 2, 2018 8:15 a.m.–5:30 p.m. Sunday, June 3, 2018 8:30 a.m.–12:35 p.m. Learn more at pgcourse.gastro.org.

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LETTER FROM THE EDITOR: Hope, hepatology, and social determinants of health

elcome to the April edition effectiveness of new IBD drugs. You Economic pressures are leading to massive consolidations of GI & Hepatology News. can also read about incorporating WApril has always been a psychological care in the manage- within the health care delivery system. month in which we have a sense ment of chronic diseases – a topic of renewal and becoming more important as we 340-B funding, continued transition integrations now have supplanted hope. For those expand our focus beyond just the from commercial to government horizontal integrations as the indus- of us living in biology of disease and into social payers, a tightening labor market, try trend. This situation will affect northern climes, determinants of health as we con- and relentless increases in overhead many of our independent gastroen- both the dis- tinue our transition to value-based expenses, all combine to reduce terology practices as demand-side tinct change in reimbursement. Another topic financial margins of both academic management by large national cor- daylight and the included this month (and to which and nonacademic health systems. porations increases. melting of the several DDW sessions are dedicat- Economic pressures are leading to snow (finally) ed) is the devastating impact of opi- massive consolidations within the John I. Allen, MD, MBA, AGAF both lift us from ates on our patients. health care delivery system. Vertical Editor in Chief the doldrums DR. ALLEN We have included a number of of winter dark- hepatology articles this month, DATA WATCH ness. such as the front-page story on In just over 2 months, we will NASH and its relationship with Prevalence of chronic conditions by IBD status gather in Washington for Digestive hepatocellular cancer. Pioglitazone Disease Week.® I have seen a pre- benefits NASH patients with and view of AGA plenary sessions (basic without type 2 diabetes, and bio- Arthritis science and clinical). They will be markers may predict liver trans- terrific. We will hear about advanc- plant failures. There are selected Respiratory disease es in areas such as the microbiome, articles about Barrett’s esophagus IBD-related inflammatory path- progression and risk stratification Ulcer ways, new insights into functional for colorectal cancer. bowel disorders, and a myriad of From Washington, we have re- Cardiovascular disease new therapeutics (both medical ceived some good news. Please see Adults with IBD and device) for us to share with our the AGA commentary on the pro- Cancer patients. posed budget. We were reminded Adults without IBD In this month’s issue, we touch recently about how federal politics Diabetes* on themes that will carry into DDW. can impact U.S. medicine. With EWS Substantial work is being done to the (very late) reauthorization of 0 5% 10% 15% 20% 25% 30% 35% 40% N

better define an IBD severity index. the Children’s Health Insurance EDICAL *Difference is not signicant These metrics are of critical impor- Plan (CHIP), we saw how political M Note: Based on data from the National Health Interview Survey, 2015 and 2016. tance for clinical researchers to use dysfunction can impact millions of Source: MMWR. 2018;67(6):190-5 RONTLINE as we investigate the efficacy and American family’s lives. Changes in F

EDITOR IN CHIEF GI & HEPATOLOGY NEWS is the ofcial newspaper of the American FRONTLINE MEDICAL COMMUNICATIONS SOCIETY PARTNERS John I. Allen, MD, MBA, AGAF Gastroenterological Association (AGA) Institute and provides the VP/Group Publisher; Director, FMC Society Partners Mark Branca ASSOCIATE EDITORS gastroenterologist with timely and relevant news and commentary about Editor in Chief Mary Jo M. Dales clinical developments and about the impact of health care policy. Content for Megan A. Adams, MD, JD, MSc Executive Editors Denise Fulton, Kathy Scarbeck GI & HEPATOLOGY NEWS is developed through a partnership of the newspaper’s Editor Lora T. McGlade Ziad Gellad, MD, MPH, AGAF medical board of editors (Editor in Chief and Associate Editors), Frontline Kim L. Isaacs, MD, PhD, AGAF Creative Director Louise A. Koenig Medical Communications Inc. and the AGA Institute Staff. “News from the Bryson Katona, MD, PhD AGA” is provided exclusively by the AGA, AGA Institute, and AGA Research Director, Production/Manufacturing Rebecca Slebodnik Gyanprakash A. Ketwaroo, MD, MSc Foundation. All content is reviewed by the medical board of editors for National Account Manager Artie Krivopal, 973-206-2326, Larry R. Kosinski, MD, MBA, AGAF accuracy, timeliness, and pertinence. To add clarity and context to important cell 973-202-5402, [email protected] Sonia S. Kupfer, MD developments in the eld, select content is reviewed by and commented on by Digital Account Manager Rey Valdivia, 973-206-8094, Wajahat Mehal, MD, PhD external experts selected by the board of editors. [email protected] Senior Director of Classied Sales Tim LaPella, 484-921-5001, [email protected] EDITORS EMERITUS The ideas and opinions expressed in GI & HEPATOLOGY NEWS do not Colin W. Howden, MD, AGAF necessarily reect those of the AGA Institute or the Publisher. The AGA Advertising Ofces 7 Century Drive, Suite 302, Parsippany, NJ 07054-4609 973-206-3434, fax 973-206-9378 Charles J. Lightdale, MD, AGAF Institute and Frontline Medical Communications Inc. will not assume MEDICAL COMMUNICATIONS AGA INSTITUTE STAFF responsibility for damages, loss, or claims of any kind arising from or related FRONTLINE to the information contained in this publication, including any claims related GI & HEPATOLOGY NEWS, Vice President, Marketing & Customer Managing Editor, Brook A. Simpson to the products, drugs, or services mentioned herein. Advertisements do Chairman Stephen Stoneburn President/CEO Alan J. Imhoff Advocacy Jim McDonough Managing Editor, THE NEW GASTROENTEROLOGIST, Ryan A. Farrell not constitute endorsement of products on the part of the AGA Institute or CFO Douglas E. Grose Vice President, Operations Jim Chicca Special Content Editor Lindsey M. Brounstein Frontline Medical Communications Inc. Vice President, Sales Mike Guire Senior Publications Coordinator Jillian L. Schweitzer President, Digital Douglas E. Grose Vice President, Society Partners Chief Digital Ofcer Lee Schweizer Vice President of Publications Erin C. Landis POSTMASTER Send changes of address (with old mailing Mark Branca Vice President, Digital Publishing Circulation Director Jared Sonners OFFICERS OF THE AGA INSTITUTE label) to GI & Hepatology News, Subscription Service, 151 Amy Pfeiffer Corporate Director, Research & Fairchild Ave., Suite 2, Plainview, NY 11803-1709. President Sheila E. Crowe, MD, AGAF President, Custom Solutions JoAnn Wahl Communications Lori Raskin Editor in Chief Mary Jo M. Dales President-Elect David A. Lieberman, MD, AGAF The AGA Institute headquarters is located at 4930 Del Ray Vice President, Custom Programs Vice President Hashem B. El-Serag, MD, MPH, AGAF Avenue, Bethesda, MD 20814, [email protected]. Carol Nathan Secretary/Treasurer Francis M. Giardiello, MD, AGAF Editorial Ofces 2275 Research Blvd, Suite 400, Rockville, MD Vice President, Custom Solutions Wendy In afliation with Global Academy for 20850, 240-221-2400, fax 240-221-2548 Scan this QR Raupers Medical Education, LLC Code to visit Senior Vice President, Finance ©2018 by the AGA Institute. All rights reserved. No part of this publication GI & HEPATOLOGY NEWS (ISSN 1934-3450) is published monthly for Vice President, Medical Education & gihepnews.com Steven J. Resnick may be reproduced or transmitted in any form or by any means, electronic or $230.00 per year by Frontline Medical Communications Inc., Conferences Sylvia H. Reitman, MBA Vice President, Human Resources & Vice President, Events David J. Small, mechanical, including photocopy, recording, or any information storage and 7 Century Drive, Suite 302, Parsippany, NJ 07054-4609. Facility Operations Carolyn Caccavelli retrieval system, without permission in writing from the publisher. Phone 973-206-3434, fax 973-206-9378 MBA # 1 MOST PRESCRIBED, BRANDED BOWEL PREP KIT1

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

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

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

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

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

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

GIHEP_3.indd 1 10/12/2017 2:37:35 PM 4 NEWS APRIL 2018 • GI & HEPATOLOGY NEWS FDA issues warning to duodenoscope manufacturers

BY LORI LAUBACH turers for failing to comply with the The warning is part of an on- Fujifilm, and Pentax – are required Frontline Medical News requirements of federal law under going effort to prevent patient to conduct studies to sample and which they were ordered to conduct infections associated with the culture reprocessed duodeno- he Food and Drug Administra- postmarket surveillance studies to transmission of bacteria from con- scopes that are in clinical use to tion issued warning letters to all assess the effectiveness of reprocess- taminated duodenoscopes. The learn more about issues that con- Tthree duodenoscope manufac- ing the devices. three manufacturers – Olympus, tribute to contamination, and to study human factors to determine how hospital staff who have had training are following the reprocessing instructions. In 2015, the FDA ordered the companies to conduct a postmarket surveillance study to determine whether health care facilities were able to properly clean and disinfect the devices.

If the companies fail to respond to the warning letter, the FDA states that they may IMPORTANT SAFETY INFORMATION take additional action, such SUPREP® Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults. Most common adverse reactions (>2%) are overall discomfort, abdominal distention, abdominal pain, nausea, vomiting and headache. as seizure, injunction, and Use is contraindicated in the following conditions: gastrointestinal (GI) obstruction, bowel perforation, toxic colitis and toxic megacolon, gastric retention, ileus, known allergies to components of the kit. Use civil monetary penalties. caution when prescribing for patients with a history of seizures, arrhythmias, impaired gag reflex, regurgitation or aspiration, severe active ulcerative colitis, impaired renal function or patients taking medications that may affect renal function or electrolytes. Use can cause temporary elevations in uric acid. Uric acid fluctuations in patients with gout may precipitate an acute flare. Administration of osmotic laxative products may produce mucosal aphthous ulcerations, and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Patients with impaired water handling who experience severe vomiting Currently, the Olympus manufac- should be closely monitored including measurement of electrolytes. Advise all patients to hydrate adequately before, during, and after use. Each bottle must be diluted with water to a final volume of 16 ounces turer has failed to start data collec- and ingestion of additional water as recommended is important to patient tolerance. tion, while both Pentax and Fujifilm have failed to provide sufficient data required for their respective BRIEF SUMMARY: Before prescribing, please see Full Prescribing Information and Medication Guide for SUPREP® Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution. INDICATIONS AND USAGE: An osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults. CONTRAINDICATIONS: Use is contraindicated in the following studies to sample and culture re- conditions: gastrointestinal (GI) obstruction, bowel perforation, toxic colitis and toxic megacolon, gastric retention, ileus, known allergies to components of the kit. WARNINGS AND PRECAUTIONS: processed duodenoscopes that are SUPREP Bowel Prep Kit is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults. Use is contraindicated in the following conditions: gastrointestinal (GI) obstruction, in clinical use. In addition, Olympus bowel perforation, toxic colitis and toxic megacolon, gastric retention, ileus, known allergies to components of the kit. Use caution when prescribing for patients with a history of seizures, arrhythmias, impaired and Pentax have not complied with gag reflex, regurgitation or aspiration, severe active ulcerative colitis, impaired renal function or patients taking medications that may affect renal function or electrolytes. Pre-dose and post-colonoscopy ECGs requirements to assess how well should be considered in patients at increased risk of serious cardiac arrhythmias. Use can cause temporary elevations in uric acid. Uric acid fluctuations in patients with gout may precipitate an acute flare. Administration of osmotic laxative products may produce mucosal aphthous ulcerations, and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Patients with impaired water staff members have followed the handling who experience severe vomiting should be closely monitored including measurement of electrolytes. Advise all patients to hydrate adequately before, during, and after use. Each bottle must be diluted reprocessing instructions after the with water to a final volume of 16 ounces and ingestion of additional water as recommended is important to patient tolerance. Pregnancy: Pregnancy Category C. Animal reproduction studies have not been human factors studies and Fujifilm conducted. It is not known whether this product can cause fetal harm or can affect reproductive capacity. Pediatric Use: Safety and effectiveness in pediatric patients has not been established. Geriatric has been meeting its requirements Use: Of the 375 patients who took SUPREP Bowel Prep Kit in clinical trials, 94 (25%) were 65 years of age or older, while 25 (7%) were 75 years of age or older. No overall differences in safety or for its human factors study only. effectiveness of SUPREP Bowel Prep Kit administered as a split-dose (2-day) regimen were observed between geriatric patients and younger patients. DRUG INTERACTIONS: Oral medication administered within one hour of the start of administration of SUPREP may not be absorbed completely. ADVERSE REACTIONS: Most common adverse reactions (>2%) are overall discomfort, abdominal distention, “The FDA has taken important abdominal pain, nausea, vomiting and headache. Oral Administration: Split-Dose (Two-Day) Regimen: Early in the evening prior to the colonoscopy: Pour the contents of one bottle of SUPREP steps to improve the reprocessing Bowel Prep Kit into the mixing container provided. Fill the container with water to the 16 ounce fill line, and drink the entire amount. Drink two additional containers filled to the 16 ounce line with water over the of duodenoscopes, and we’ve seen next hour. Consume only a light breakfast or have only clear liquids on the day before colonoscopy. Day of Colonoscopy (10 to 12 hours after the evening dose): Pour the contents of the second a reduction in reports of patient in- SUPREP Bowel Prep Kit into the mixing container provided. Fill the container with water to the 16 ounce fill line, and drink the entire amount. Drink two additional containers filled to the 16 ounce line with water fections, but we need the required over the next hour. Complete all SUPREP Bowel Prep Kit and required water at least two hours prior to colonoscopy. Consume only clear liquids until after the colonoscopy. STORAGE: Store at 20°-25°C (68°-77°F). Excursions permitted between 15°-30°C (59°-86°F). Rx only. Distributed by Braintree Laboratories, Inc. Braintree, MA 02185. postmarket studies to determine whether these measures are being properly implemented in real-world clinical settings and whether we need to take additional action to further improve the safety of these devices,” said Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health in a press release. For additional information, please call 1-800-874-6756 or visit www.suprepkit.com The companies had until March 24 to submit a plan that outlines how study milestones will be achieved. If the companies fail to respond to the ©2017 Braintree Laboratories, Inc. All rights reserved. HH13276AT-U May 2017 warning letter, the FDA states that they may take additional action, such as seizure, injunction, and civil monetary penalties. Read the full press release on the FDA’s website.

[email protected] GIHEPNEWS.COM • APRIL 2018 NEWS 5 Congressional budget includes AGA wins

BY JOHN W. GARRETT, MD, MS, AGAF, us and the medical community and would prefer this reduction not be time to submit and receive a hard- AGA PRACTICE COUNCILLOR, MISSION taking action. included, it is much better than the ship exemption from the current HEALTH, ASHEVILLE, N.C. misvalued codes provision, which EHR standards that would apply Misvalued codes disproportionately impacts special- to meaningful use and the Quality GA spends a lot of time on AGA and the physician community ties, like gastroenterology. Payment Program’s advancing care Capitol Hill advocating to help were also successful in removing a information performance category. Agastroenterologists in prac- provision that would have extended Geographic Practice Cost Index tice better care for their patients the misvalued The budget agreement extends the Biosimilars coverage and receive fair reimbursement. codes initiative work for the Geographic Practice under Medicare Part D Therefore, we were pleased that for the next two Cost Index (GPCI) floor for two The agreement also levels the play- the budget deal passed by Congress years to real- additional years, which avoids a ing field between biologics and and signed by the president in Feb- locate savings decrease in Medicare reimburse- biosimilars by adding biosimilars ruary included several policy vic- from potential- ment for physicians that practice in to the Medicare Coverage Gap Dis- tories that AGA has been working ly overvalued rural areas. The work GPCI is a vari- count Program. Additionally, by diligently on for many years. codes. AGA, able that Medicare uses to adjust providing the 50 percent discount the Alliance of the work component of physician equally, beneficiary out-of-pocket IPAB repeal Specialty Med- payment based on where they live. costs will be reduced and the Medi- AGA, and all of organized medicine, DR. GARRETT icine and the A work GPCI floor of 1.0 protects care program will save money as a have long opposed the Independent AMA opposed physicians in low-cost, often rural result of covering the less expensive Payment Advisory Board (IPAB) that the original provision expanding areas, from being paid less for the medication. was created as part of the Afford- the misvalued codes initiative and work they do. able Care Act. IPAB is an unelected, have argued that virtually all codes AGA and the medical community unaccountable board whose sole under the fee schedule, including Meaningful use standards have fought long and hard for these purpose is to cut Medicare spending gastroenterology, have been re- The package addresses electronic provisions and are happy to see from providers should Medicare evaluated and have already faced health record (EHR) standards and them finally being implemented. We reach a certain threshold of spend- significant cuts. In the final agree- eases requirements for physicians. thank all of our members who have ing. Since hospitals are exempt from ment, Congress eliminated recap- The language removes the man- worked along with us to ensure their purview, physicians would turing savings from the misvalued date that meaningful use standards that the voice of gastroenterology be particularly vulnerable to cuts. codes initiative and instead lowered become more stringent over time, continues to be heard on Capitol However, repealing IPAB has had bi- overall updates for physician reim- which is a major financial burden Hill. partisan support over the years, and bursement under Medicare by .25 for physician practices. The lan- we applaud Congress for listening to percent for 1 year. Although AGA guage also gives physicians more [email protected]

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Discover monumental developments in science and medicine at Digestive Disease Week® (DDW) 2018. DDW generates and shares capital ideas for global impact in the ﬁ elds of gastroenterology, REGISTER BY APRIL 18 AND SAVE AT LEAST $80. hepatology, GI Jan. 17, 2018 AASLD, AGA, ASGE and SSAT endoscopy members-only registration opens. and GI surgery. Jan. 24, 2018 General registration opens. Attend DDW 2018 in Washington, DC. DDW On Demand is Included with Registration! Register today at nppa.gastro.org. Get access to the online digital presentations from DDW 2018 so you don’t miss a single session.. 2680-285EDU_18-1 2680-285EDU_17-2 6 NEWS APRIL 2018 • GI & HEPATOLOGY NEWS FROM THE AGA JOURNALS Bioengineered liver models screen drugs

BY CHHAVI JAIN dependent on imaging-based read- Frontline Medical News outs and have a limited ability to in- Thirty to 50 new drugs are ap- vironment). These in vitro systems vestigate cell responses to gradients proved in the United States annu- have not only enabled investigators ioengineered liver models have of microenvironmental signals. ally, which costs approximately to screen multiple drugs at the enabled recapitulation of liver Liver development, physiology, and $2.5 billion/drug in drug devel- same time but also have informed Barchitecture with precise con- pathophysiology are dependent on opment costs. Nine out the clinical translation of trol over cellular microenvironments, homotypic and heterotypic interac- of 10 drugs never make these technologies. For resulting in stabilized liver functions tions between parenchymal and non- it to market, and of example, the extracorpo- for several weeks in vitro. Studies parenchymal cells (NPCs). Cocultures those that do, adverse real liver assist device – have focused on using these models with both liver- and nonliver-derived events affect their lon- essentially, a liver bypass to investigate cell responses to drugs NPC types, in vitro, can induce liver gevity. Hepatotoxicity – and similar bioartificial and other stimuli (for example, vi- functions transiently and have proven is the most frequent liver devices can in prin- ruses and cell differentiation cues) to useful for investigating host respons- adverse drug reaction, cipal temporarily per- predict clinical outcomes. Gregory H. es to sepsis, mutagenesis, xenobiotic and drug-induced liver form some of the major Underhill, PhD, from the department metabolism and toxicity, response injury, which can lead liver functions while a pa- of bioengineering at the University to oxidative stress, lipid metabolism, to acute liver failure, DR. CARR tient’s native liver heals of Illinois at Urbana-Champaign and and induction of the acute-phase occurs in a subset of from drug-induced liver Salman R. Khetani, PhD, from the response. Micropatterned cocultures affected patients. Understanding injury or other hepatic injury. department of bioengineering at (MPCCs) are designed to allow the a drug’s risk of hepatotoxicity be- However, just as we have seen the University of Illinois in Chicago use of different NPC types without fore patients start using it can not with the limitations of the in vitro presented a comprehensive review significantly altering hepatocyte only save lives but also conceivably systems, bioartificial livers are un- of these advances in bioengineered homotypic interactions. Cell-cell in- reduce the costs incurred by phar- likely to be successful unless they liver models in Cellular and Molecu- teractions can be precisely controlled maceutical companies, which are integrate the liver’s complex func- lar Gastroenterology and Hepatology to allow for stable functions for up to passed on to consumers. tions of protein synthesis, immune (doi: 10.1016/j.jcmgh.2017.11.012). 4-6 weeks, whereas more randomly In Cellular and Molecular Gas- surveillance, energy homeostasis, Drug-induced liver injury is a distributed cocultures have limited troenterology and Hepatology, and nutrient sensing. The future is leading cause of drug attrition in the stability. Unlike randomly distributed Underhill and Khetani summarize bright, though, as biomedical sci- United States, with some marketed cocultures, MPCCs can be infected available and emerging cell-based, entists and bioengineers continue drugs causing cell necrosis, hepati- with HBV, HCV, and malaria. high-throughput systems that can to push the envelope by advancing tis, cholestasis, or fibrosis. Although Randomly distributed spheroids or be used to predict hepatotoxicity. both in vitro and bioartificial tech- the Food and Drug Administration organoids enable 3-D establishment These modalities include cellular nologies. requires preclinical drug testing in of homotypic cell-cell interactions microarrays of single cells, cocul- animal models, differences in spe- surrounded by an extracellular ma- tures of liver parenchymal and Rotonya Carr, MD, is an assistant cies-specific drug metabolism and trix. The spheroids can be further nonparenchymal cells, organoids professor of medicine in the division human genetics may result in inad- cocultured with NPCs that facilitate (3-D organ-like structures), and of gastroenterology at the Univer- equate identification of potential for heterotypic cell-cell interactions and liver-on-a-chip devices (complex sity of Pennsylvania, Philadelphia. human drug-induced liver injury. allow the evaluation of outcomes re- perfusion bioreactors that allow for She receives research support from Some bioengineered liver models for sulting from drugs and other stimuli. modulation of the cellular microen- Intercept Pharmaceuticals. in vitro studies are based on tissue Hepatic spheroids maintain major engineering using high-throughput liver functions for several weeks and microarrays, protein micropattern- have proven to be compatible with control of cell placement. ing away of built-up beneficial mole- ing, microfluidics, specialized plates, multiple applications within the drug Another bioengineered liver mod- cules with perfusion. biomaterial scaffolds, and bioprint- development pipeline. el is based on perfusion systems The ongoing development of more ing. These spheroids showed greater or bioreactors that enable dynamic sophisticated engineering tools for High-throughput cell microarrays sensitivity in identifying known fluid flow for nutrient and waste manipulating cells in culture will lead enable systematic analysis of a large hepatotoxic drugs than did short- exchange. These so called liver-on- to advances in bioengineered livers number of drugs or compounds at term primary human hepatocyte a-chip devices contain hepatocyte that will show improving sensitivity a relatively low cost. Several culture (PHH) monolayers. PHHs secreted aggregates adhered to collagen- for the prediction of clinically rele- platforms have been developed us- liver proteins, such as albumin, coated microchannel walls; these vant drug and disease outcomes. ing multiple sources of liver cells, transferrin, and fibrinogen, and are then perfused at optimal flow This work was funded by Nation- including cancerous and immortal- showed cytochrome-P450 activities rates both to meet the oxygen deal Institutes of Health grants. Dr. ized cell lines. These platforms show for 77-90 days when cultured on a mands of the hepatocytes and de- Khetani disclosed a conflict of inter- enhanced capabilities to evaluate nylon scaffold containing a mixture liver a low shear stress to the cells est with Ascendance Biotechnology, combinatorial effects of multiple of liver NPCs and PHHs. that’s similar to what would be the which has licensed the micropat- signals with independent control of Potential limitations of randomly case in vivo. Layered architectures terned coculture and related systems biochemical and biomechanical cues. distributed spheroids include ne- can be created with single-chamber from Massachusetts Institute of For instance, a microchip platform crosis of cells in the center of larger or multichamber, microfluidic de- Technology, Cambridge, and Colorado for transducing 3-D liver cell cultures spheroids and the requirement vice designs that can sustain cell State University, Fort Collins, for com- with genes for drug metabolism en- for expensive confocal microscopy functionality for 2-4 weeks. mercial distribution. Dr. Underhill zymes featuring 532 reaction vessels for high-content imaging of entire Some of the limitations of perfu- disclosed no conflicts. (micropillars and corresponding spheroid cultures. To overcome the sion systems include the potential microwells) was able to provide limitation of disorganized cell-type binding of drugs to tubing and other [email protected] information about certain enzyme interactions over time within the materials used, large dead volume combinations that led to drug toxic- randomly distributed spheroids/ requiring higher quantities of novel SOURCE: Underhill GH and Khetani SR. ity in cells. The high-throughput cell organoids, bioprinted human liver or- compounds for the treatment of cell Cell Molec Gastro Hepatol. 2017. doi: microarrays are, however, primarily ganoids are designed to allow precise cultures, low throughput, and wash- org/10.1016/j.jcmgh.2017.11.012. For rst-line constipation therapy, stick with the leader

The AGA recommends PEG laxatives (like MiraLAX) as a rst-line constipation treatment1 ✔ 96% patient satisfaction rate* ✔ #1 GI-recommended laxative for over 10 years Start with MiraLAX for proven relief of occasional constipation. *Survey of 300 consumers, 2017. Doctor recommended, Use as directed on product labeling or as directed by your doctor. Reference: 1. Clinical decision support tools. American Gastroenterological Association website. patient approved http://campaigns.gastro.org/algorithms/constipation/index.html. Accessed May 12, 2017. Bayer, the Bayer Cross, and MiraLAX are trademarks of Bayer. © 2017 Bayer May 2017 68522-PP-MLX-BASE-US-0328

7/26/2017 1:32:45 PM (*)[email protected] 1 8 NEWS APRIL 2018 • GI & HEPATOLOGY NEWS FROM THE AGA JOURNALS Pioglitazone beneted NASH patients with/without t2d

BY AMY KARON ciation guidelines. After a 4-week run-in period, status. Likewise, intrahepatic triglyceride Frontline Medical News patients were randomly assigned to receive ei- content, as measured by proton magnetic ther pioglitazone (45 mg per day) or placebo for resonance spectroscopy, fell by 11% in piogl- ioglitazone therapy given for 18 months 18 months. All patients received lifestyle coun- itazone recipients with type 2 diabetes and benefited patients with nonalcoholic ste- seling and a hypocaloric (500-kcal reduced) diet. by 9% in those with prediabetes, a nonsig - Patohepatitis (NASH) similarly, regardless Compared with placebo, pioglitazone im- nificant difference. Pioglitazone also led to a of whether they had diabetes or prediabetes, proved most secondary outcomes similarly re- statistically similar decrease in plasma alanine according to the results of a randomized pro- aminotransferase level regardless of whether spective trial. patients had type 2 diabetes (50 U/L) or were The primary outcome, at least a 2-point prediabetic (36 U/L). reduction in nonalcoholic fatty liver disease This trial’s key takeaway is that pioglitazone activity score, compared with placebo, without improves liver histology in NASH whether or worsening fibrosis, was met by 48% of NASH Compared with placebo, pioglitazone not patients are diabetic, said the researchers. patients with type 2 diabetes and by 46% of “We believed that it was essential to compare its those with prediabetes, reported Fernando Bril, improved most secondary outcomes efficacy in patients with [and] without [type 2 MD, of the division of endocrinology, diabetes, similarly regardless of whether patients diabetes] because of the vast number of patients and metabolism at the University of Florida, with prediabetes and NASH and given the sig- Gainesville, and his associates. The report was had type 2 diabetes or prediabetes. nificant metabolic and cardioprotective effects published in the April issue of Clinical Gastro- The two exceptions were brosis and of pioglitazone among patients without type enterology and Hepatology (doi: 10.1016/j. insulin sensitivity of adipose tissue. 2 diabetes,” they wrote. The natural history of cgh.2017.12.001). NASH is worse in the presence of type 2 diabe- NASH resolved completely in 44% with type tes, which might explain pioglitazone’s superior 2 diabetes and 26% of patients without it, per- gardless of whether patients had type 2 diabetes effects on fibrosis and insulin sensitivity of adi- haps indicating that pioglitazone acts slightly or prediabetes. The two exceptions were fibrosis pose tissue in this population, they added. differently when patients with NASH have type and insulin sensitivity of adipose tissue. Patients The Burroughs Wellcome Fund, the American 2 diabetes, according to the investigators. “Al- with type 2 diabetes only experienced improved Diabetes Association, and the Veteran’s Affairs though the effects on fibrosis appear to be sim- fibrosis in the setting of pioglitazone therapy (P Merit Award supported the work. Senior au- ilar in both groups, pioglitazone may contribute = .035 vs. baseline). In prediabetic patients, fi- thor Kenneth Cusi, MD, disclosed nonfinancial to halting [its] rapid progression [in type 2 brosis lessened moderately over time, regardless support from Takeda Pharmaceuticals, grants diabetes],” they wrote. “These differences will of whether they received pioglitazone or place- from Novartis and Janssen Research and Devel- deserve further exploration in larger clinical bo. Insulin sensitivity of adipose tissue improved opment, and consulting relationships with Eli trials.” much more markedly with treatment in patients Lilly, Tobira Therapeutics, and Pfizer. The other The trial (NCT00994682) enrolled 101 pa- with type 2 diabetes (P less than .001 vs. base- authors had no conflicts. tients with biopsy-confirmed NASH, of whom line) than in those with prediabetes (P = .002 for 52 had type 2 diabetes and 49 had prediabetes type 2 diabetes vs. prediabetes). [email protected] based on clinical history, baseline fasting plasma Compared with placebo, pioglitazone im- SOURCE: glucose, hemoglobin A1c, and an oral glucose proved hepatic and skeletal muscle insulin Bril F et al. Clin Gastroenterol Hepatol. 2018 Feb tolerance test, as per American Diabetes Asso- sensitivity similarly, regardless of diabetes 24. doi: 10.1016/j.cgh.2017.12.001. Biomarker predicted primary nonfunction after transplant

BY AMY KARON conventional clinical assessment” no reliable scoring systems or bio- recipients from two centers. The Frontline Medical News and also could help prevent en- markers have been able to predict most common reason for liver graftment failures. “To our knowl- these outcomes prior to trans- transplantation was decompen- ncreased donor liver perfusate edge, not a single biomarker has plantation, clinical glycomics of sated cirrhosis secondary to Ilevels of an underglycosylated demonstrated the same accuracy serum has proven useful for diag- alcoholism, followed by chronic glycoprotein predicted prima- today,” they wrote in the April is- nosing hepatic fibrosis, cirrhosis, hepatitis C or B virus infection, ry transplant nonfunction with sue of Gastroenterology. and hepatocellular carcinoma and acute liver failure, and polycystic 100% accuracy in two prospec- Chronic shortages of donor for distinguishing hepatic steato- liver disease. tive cohorts, researchers reported livers contribute to morbidity sis from nonalcoholic steatohep- Donor grafts were transported in Gastroenterology. atitis. using cold static storage (21° C), Glycomic alterations of “Perfusate biomarkers are and hepatic veins were flushed to immunoglobulin G “rep- an attractive alternative [to] collect perfusate before transplan- resent inflammatory dis- liver biopsy or serum mark- tation. Protein-linked N-glycans turbances in the liver that ers, because perfusate is were isolated from these perfusate [mean it] will fail after believed to represent the con- samples and analyzed with a mul- transplantation,” wrote Xavier and death worldwide. However, dition of the entire liver parenchy- ticapillary electrophoresis-based Verhelst, MD, of Ghent (Belgium) relaxing donor criteria is contro- ma and is easy to collect in large ABI3130 sequencer. University Hospital and his associ- versial because of the increased volumes,” the researchers wrote. The four patients in the prima- ates. The new glycomarker “could risk of primary nonfunction, Accordingly, they studied 66 ry study cohort who developed be a tool to safely select high-risk which affects some 2%-10% of patients who underwent liver primary nonfunction resembled organs for liver transplantation liver transplantation patients, and transplantation at a single center the others in terms of all clinical that otherwise would be discard- early allograft dysfunction, which in Belgium and a separate valida- and demographic parameters ex- ed from the donor pool based on a is even more common. Although tion cohort of 56 transplantation Continued on following page GIHEPNEWS.COM • APRIL 2018 NEWS 9 FROM THE AGA JOURNALS Opioids linked to mortality in inammatory bowel disease

BY AMY KARON individuals with Crohn’s disease and 5,349 Frontline Medical News patients with ulcerative colitis from Re- Balancing control of pain and prevention of searchOne, a primary care electronic health opioid-related morbidity and mortality remains mong patients with inflammatory bowel records database that covers about 10% of a major challenge for health care providers, disease (IBD), opioid prescriptions tri- patients in England. The data set excluded particularly in IBD. This study by Burr et al. Apled during a recent 20-year period, and patients with indeterminate colitis or who highlights the potential dan- heavy use of strong opioids was a significant underwent colectomy for ulcerative colitis. gers of opiate use among predictor of all-cause mortality, according to a From 1990 through 1993, only 10% of patients with IBD with the large cohort study reported in the April issue patients with IBD were prescribed opioids, finding that opioid prescrip- of Clinical Gastroenterology and Hepatology. compared with 30% from 2010 through 2013 tions at least three times Because this study was retrospective, it (P less than .005). After the investigators per year were associated could not establish causality, said Nicholas E. controlled for numerous demographic and with a two- to threefold in- Burr, MD, of the University of Leeds (England) clinical variables, being prescribed a strong crease in mortality. Another and his associates. But “[de]signing and con- opioid (morphine, oxycodone, fentanyl, bu- important observation from ducting a large-scale randomized controlled prenorphine, methadone, hydromorphone, this study was that the prev- trial may not be feasible,” they wrote. “Despite or pethidine) more than three times per year alence of opioid use among DR. HOU the limitations of observational data, popu- significantly correlated with all-cause mor- IBD patients increased from lation data sets may be the best method to tality in both Crohn’s disease (hazard ratio, 10% to 30% during 1990-2013. One would like investigate a potential effect.” 2.2; 95% confidence interval, 1.2-4.0) and ul- to believe that, with better treatment modalities The gastrointestinal side effects of many cerative colitis (HR, 3.3; 95% CI, 1.8-6.2), the for IBD, fewer patients would require chronic analgesics complicate pain management for researchers reported. opioid medications over time; however, this patients with IBD, who not only live with Among patients with ulcerative colitis, more observation suggests that there has been a shift chronic abdominal pain but also can develop moderate use of strong opioids (one to three in the perception and acceptance of opioids for arthropathy-related musculoskeletal pain, prescriptions annually) also significantly cor- IBD patients. chronic widespread pain, and fibromyalgia. related with all-cause mortality (HR, 2.4; 95% Studying opioid use among IBD patients re- In addition to the risk of narcotic bowel CI, 1.2-5.2), as did heavy use of codeine (HR, mains challenging as even well-controlled ret- syndrome associated with opioid use in IBD, 1.8; 95% CI, 1.1-3.1), but these associations rospective studies are unable to fully separate opioids can mask flares in IBD or can cause did not reach statistical significance among pa- whether opioid use is merely associated with toxic dilatation if administered during acute tients with Crohn’s disease. Tramadol was not more aggressive IBD courses and hence worse flares, the researchers noted. Because few linked to mortality in either IBD subtype when outcomes or whether opioid use directly results studies had examined opioid use in IBD, the used alone or in combination with codeine. in increased mortality. As clinicians, we are left investigators retrospectively studied 3,517 Dr. Burr and his associates said they could with the difficult balance of addressing true not control for several important potential symptoms of pain with the potential harm from confounders, including fistulating disease, opioids; we often counsel against the use of quality of life, mental illness, substance abuse, nonsteroidal anti-inflammatory medications in and history of abuse, all of which have been IBD, and yet there is growing concern about use linked to opioid use in IBD. Nonetheless, they of opioids in this same population. found dose-dependent correlations with mor- Further research is needed to address patients tality that highlight a need for pharmacovig- with pain not directly tied to inflammation or ilance of opioids in IBD, particularly given complications of IBD, as well as nonmedical, be- dramatic increases in prescriptions, they said. havioral approaches to pain management. These were primary care data, which tend to accurately reflect long-term medication use, Jason K. Hou, MD, MS, is an investigator in the they noted. clinical epidemiology and outcomes program, Crohn’s and Colitis U.K. and the Leeds Teach- Center for Innovations in Quality, Effectiveness ing Hospitals NHS Trust Charitable Foundation and Safety at the Michael E. DeBakey VA Med- provided funding. The investigators reported ical Center, Houston; an assistant professor, having no conflicts of interest. department of medicine, section of gastroenterology & hepatology, Baylor College of Medicine, [email protected] Houston; and a codirector of Inflammatory HINKSTOCK

/T Bowel Disease Center at the VA Medical Center SOURCE: Burr NE et al. Clin Gastroenterol Hepatol. 2017. at Baylor. He has no conflicts. IDERINA

L doi: 10.1016/j.cgh.2017.10.022.

Continued from previous page tion of NGA2F (P = .037). There The researchers found no spe- Organizations that provided were no false positives in either cific glycomic signature for early funding included the Research cept that they had a markedly in- cohort, and a 13% cutoff for per- allograft dysfunction, perhaps be- Fund – Flanders and Ghent Uni- creased concentration (P less than fusate NGA2F level identified cause it is more complex and mul- versity. The researchers reported .0001) of a single-glycan, agalacto primary nonfunction with 100% tifactorial, they wrote. Although having no conflicts of interest. core-alpha-1,6-fucosylated bian- accuracy, the researchers said. In electrophoresis testing took 48 tennary glycan, dubbed NGA2F. a multivariable model of donor hours, work is underway to short- [email protected] The single patient in the val- risk index and perfusate markers, en this to a “clinically acceptable idation cohort who developed only NGA2F was prognostic for time frame,” they added. They rec- SOURCE: Verhelst X et al. Gastroenter- primary nonfunction also had a developing primary nonfunction ommended multicenter studies to ology. 2018 Jan 6. doi: 10.1053/j.gas- significantly increased concentra- (P less than .0001). validate their findings. tro.2017.12.027. 10 NEWS APRIL 2018 • GI & HEPATOLOGY NEWS FROM THE AGA JOURNALS Model predicted Barrett’s esophagus progression

BY AMY KARON a median of 6 years at five centers Frontline Medical News in the United States and one center Barrett’s esophagus (BE) is the similar to other risk-scoring mech- in the Netherlands. At baseline, pa- only known precursor lesion anisms, such as the MELD score for scoring model encompassing tients were an average of 55 years to esophageal adenocarcinoma progression in liver disease. just four traits accurately old (standard deviation, 20 years), (EAC), a rapidly rising cancer in With use of a large multicenter Apredicted which patients 84% were men, 88% were white, the Western world, cohort of patients with with Barrett’s esophagus were and the average Barrett’s esopha- which has a poor 5-year BE (more than 4,500 most likely to develop high-grade gus length was 3.7 cm (SD, 3.2 cm). survival rate of less than patients), this is the dysplasia or esophageal adenocar- The researchers created the 20%. Management strat- first risk-prediction cinoma, researchers reported in model by starting with many demo- egies to affect EAC inci- score developed and the April issue of Gastroenterology graphic and clinical candidate vari- dence include screening validated using base- (2017 Dec 19. doi: 10.1053/j.gas- ables and then by using backward and surveillance, with line demographic and tro.2017.12.009). selection to eliminate those that did current guidelines rec- endoscopy information Those risk factors included sex, not predict progression with a P ommending surveillance to determine risk of smoking, length of Barrett’s esoph- value of .05 or less. This is the same for all patients with a progression. Readily agus, and the presence of baseline method used in the Framingham diagnosis of BE. DR. SHARMA available factors such low-grade dysplasia, said Sravanthi Heart Study, they noted. In all, 154 However, there are as patient sex, smoking Parasa, MD, of Swedish Medical patients (6%) with Barrett’s esoph- several challenges associated status, BE length, and confirmed Center, Seattle, and her associates. agus developed high-grade dyspla- with adopting BE surveillance histology were identified as risk For example, a male with a history sia or esophageal adenocarcinoma, for all patients: It is estimated factors for progression, which of smoking found to have a 5-cm, with an annual progression rate of that anywhere from 2 million to could then generate a score de- nondysplastic Barrett’s esophagus about 1%. The significant predic- 5 million U.S. adults may harbor termining the individual patient’s on histology during his index en- tors of progression included male BE, and the overall risk of BE risk of progression. Such a simple doscopy would fall into the model’s sex, smoking, length of Barrett’s progression to EAC is low (ap- scoring system has the potential intermediate risk category, with a esophagus, and low-grade dysplasia proximately 0.2%-0.4% annually). of tailoring management based 0.7% annual risk of progression to at baseline. A model that included Both of these factors influence the on the risk factors. In the future, high-grade dysplasia or esophageal only these four variables distin- cost-effectiveness of a global BE inclusion of molecular biomarkers adenocarcinoma, they explained. guished progressors from nonpro- surveillance program. along with this score may further “This model has the potential to gressors with a c statistic of 0.76 Hence, a risk-stratification score enhance its potential for person- complement molecular biomarker (95% confidence interval, 0.72- that can distinguish BE patients alized medicine in BE patients. panels currently in development,” 0.80; P less than .001). Using 30% who are at high risk for progression they wrote. of patients as an internal validation to high-grade dysplasia (HGD) and/ Prateek Sharma, MD, is a professor Barrett’s esophagus increases the cohort, the model’s calibration or EAC from those whose disease of medicine of University of Kan- risk of esophageal adenocarcinoma slope was 0.99 and its calibration will not progress will be extreme- sas, Kansas City. He has no con- by anywhere from 30 to 125 times, intercept was -0.09 cohort (perfect- ly useful. This concept would be flicts of interest. a range that reflects the multifacto- ly calibrated models have a slope of rial nature of progression and the 1.0 and an intercept of 0.0). hypothesis that not all patients with Therefore, the model was well ognize that there is a key interest coinvestigator disclosed ties to Barrett’s esophagus should undergo calibrated and did an appropriate in contemporary medical research Cook Medical, CDx Diagnostics, and the same frequency of endoscopic job of identifying risk groups, the whether a marker (e.g. molecular, Cosmo Pharmaceuticals. surveillance, said the researchers. investigators concluded. Given genetic) could add to incremental To incorporate predictors of pro- that the overall risk of Barrett’s value of a risk progression score,” [email protected] gression into a single model, they esophagus progression is low, using they wrote. “This can be an area of analyzed prospective data from this model could help avoid excess future research.” SOURCE: Parasa S et al. Gastroenterol- nearly 3,000 patients with Barrett’s costs and burdens of unnecessary There were no funding sources. ogy. 2017 Dec 19. doi: 10.1053/j.gas- esophagus who were followed for surveillance, they added. “We rec- Dr. Parasa had no disclosures. One tro.2017.12.009.

Quick quiz

Q1. The CagA strain of Helicobacter pylori is low-grade fever, and nausea. He is seen at the following: hepatitis A IgM negative, HBsAg associated with which of the following? student health center at his university. His negative, Anti-HBc IgM negative, anti-nuclear A. A decreased response to clarithromycin- eyes are noted to be icteric, his mental status antibody negative, anti–smooth muscle anti- based therapy is intact, and he is without asterixis. He does body negative, and hepatitis E IgM positive. B. A decreased risk of duodenal ulcers not drink alcohol, take medications, or use any C. A decreased risk of gastroesophageal reflux supplements. He has no recent sexual part- What is the best next step in the treatment of disease ners. He has right upper quadrant tenderness. this patient? D. A decreased risk of esophageal squamous There are no findings to suggest chronic liver A. Pegylated interferon cell carcinoma disease. His alanine aminotransferase is 4,150 B. Ribavirin E. An increased risk of gastric carcinoid tumor U/L, his aspartate aminotransferase is 2,132 C. Observation U/L, bilirubin is 7.8 mg/dL, and he has no INR D. Entecavir Q2. A 23-year-old man returns from a wed- available. He is then referred urgently to the ding in Nepal and feels unwell with malaise, liver clinic. Additional labs are notable for the The answers are on page 24. GIHEPNEWS.COM • APRIL 2018 NEWS FROM THE AGA 11 Remember the AGA Four new and noteworthy Research Foundation in IBD drug studies

nflammatory bowel disease bo. These results provide evidence your will or living trust (IBD) is a vibrant area of clinical of JAK inhibition for the treatment Iresearch. Many of the 250+ ab- of Crohn’s disease and support fur- hat if all you had to do cific item, a set amount of stracts presented at the inaugural ther investigation. to ensure that the AGA money, or a percentage of your Crohn’s & Colitis Congress — a WResearch Foundation estate. You can also make your partnership of the Crohn’s & Colitis Rened population pharmacokinetic can have an impact for years to gift contingent upon certain Foundation and AGA — looked at model for iniximab precision dosing come is to write a simple sen- events. the efficacy and safety of IBD ther- in pediatric inammatory bowel dis- tence? Sound impossible? We hope you’ll consider in- apies. Below is a summary of four ease The AGA Research Founda- cluding a gift to the AGA Re- noteworthy drug studies from the By Laura E. Bauman, Cincinnati Chil- tion provides a key source of search Foundation in your will Congress, as determined by the Con- dren’s Hospital Medical Center, et al. funding at a critical juncture in or living trust. It’s simple – just gress organizing committee. You can Significance: Long-term clinical the careers of young investiga- a few sentences in your will or review all abstracts presented at the remission from IBD with anti-TNF tors. Securing the future of the trust are all that is needed. The Crohn’s & Colitis Congress in Gastro- therapies has generally been limited talented investigators we serve official bequest language for the enterology. to less than half of the treated pa- really is as simple as writing AGA Research Foundation is: “I, tients. Improved outcomes are seen one sentence. By including a gift [name], of [city, state, ZIP], give, Double-blind, randomized, place- with optimal pre-infusion trough to the AGA Research Foundation devise and bequeath to the AGA bo-controlled, crossover trial to eval- drug levels, a measurement of the in your will, you can support Research Foundation [written uate induction of clinical response in level of drugs in the patient’s blood- our mission tomorrow without amount or percentage of the patients with moderate-severe Crohn’s stream. However, standard weight- giving away any of your assets estate or description of proper- disease treated with rifaximin based dosing for pediatric patients today. ty] for its unrestricted use and By Scott D. Lee, University of Wash- has provided widely varying trough Including the AGA Research purpose.” ington Medicine, et al. drug levels. The investigators report Foundation in your will is a pop- Join others in donating to the Significance: It is now known that the development of a multifactorial ular gift to give because it is: AGA Research Foundation and the intestinal microbiome is in- pharmacokinetic model for predict- • Affordable. The actual giving of help fill the funding gap and tegral to the pathogenesis of IBD. ing infliximab trough levels during your gift occurs after your life- protect the next generation of However, antibiotic treatments for maintenance therapy for IBD. Such time, so your current income investigators. IBD have previously shown limited dynamic approaches to treatment is not affected. Please contact us for more effectiveness. In this 8-week clinical address a specific gap in pediatric • Flexible. Until your will goes information at foundation@ trial, there was a fourfold greater IBD therapeutic strategies. into effect, you are free to al- gastro.org or visit http://gastro. response to the antibiotic rifaximin ter your plans or change your planmylegacy.org/. in Crohn’s disease treatment, com- Primary nonresponse to tumor necro- mind. pared with placebo. The positive sis factor antagonists is associated • Versatile. You can give a spe- [email protected] impact on clinical disease activity with inferior response to second-line was seen even in patients with a biologics in patients with inamma- significant disease burden and prior tory bowel diseases: A systematic exposure to one or more biologic review and meta-analysis How to talk with your therapies. Quality of life and labora- By Siddharth Singh, University of tory measurements were numerical- California San Diego Health, et al. patients about PPIs and ly improved. No new safety concerns Significance: Primary nonresponse were identified. These results offer to anti-TNF therapy is seen in 35%- renewed hope for the use of antibi- 65% of IBD patients and another cognitive decline otics in treating Crohn’s disease. 40%-60% lose responsiveness 2018 study published in echoes that offered by AGA and during the first year of treatment. AClinical Gastroenterology and ABIM in the Choosing Wisely Post-hoc analysis of tofacitinib Physicians struggle with what Hepatology, “Lack of association campaign. Crohn’s disease phase 2 induction treatments to recommend for these between proton pump inhibitor • Educate patients not to ask efcacy in subgroups with baseline patients. The investigators in this use and cognitive decline,” found “what side effects do PPIs endoscopic or biomarker evidence of study performed a literature search no association between PPI use have?” but rather “is it really inammation and identified eight randomized con- and cognitive decline in analyz- indicated?” Reassure patients By Bruce E. Sands, Icahn School of trolled trials of biologics in patients ing data from two large popula- that, when PPIs are indicated, Medicine at Mount Sinai, et al. with prior exposure to anti-TNF and tion-based studies in Denmark. benefits outweigh risks. Significance: Tofacitinib, a Janus ki- compared outcomes based on their While this data is reassuring, cli- • Keep conversation channels nase (JAK) inhibitor, is under inves- prior responses to anti-TNF. The nicians should continue to antici- open with patients. When pa- tigation for treatment of ulcerative analysis reveals a 24% decrease in pate questions from their patients tients require long-term use of colitis and Crohn’s disease. To date, likelihood to achieve remission in about the risks associated with PPIs, the medication should not response rates in ulcerative colitis patients who changed medications PPI therapy. AGA recommends be stopped without a discussion have been higher than for Crohn’s because of immediate nonresponse the following tips for talking with with you about the risks and disease. In this report, investigators compared to loss of responsiveness your patients. benefits. performed post-hoc analysis stud- or intolerance during the treatment. • Reassure patients that you • Recommend that patients also ies using objective baseline criteria These findings raise important prescribed a PPI for a clear-cut consider life-style modifications of disease activity. Their findings questions about the biology of IBD, indication, in the lowest possi- that may reduce or eliminate the showed a greater proportion of including the pharmacology of an- ble dose, and for an appropriate need for PPIs for long-term use. patients with moderate to severe ti-TNF in a subset of patients. period of time (lowest dose, Crohn’s disease were in remission shortest time). This advice [email protected] with tofacitinib compared to place- [email protected] 12 NEWS FROM THE AGA APRIL 2018 • GI & HEPATOLOGY NEWS Better manage acute CLINICAL CHALLENGES AND IMAGES pancreatitis to improve What is your diagnosis? By Jordan Orr, MD, and Charles diarrhea, melena, hematoche- O. Elson III, MD. Published pre- zia, dysuria, or hematuria. Vital patient outcomes viously in Gastroenterology signs and abdominal physical (2016;151[2]:241-2). examination were normal. Fur- GA has a new clinical guide- duce practice variation and pro- ther, laboratory testing was un- line on the initial manage- mote high-quality and high-value 67-year-old man presented remarkable including a normal Ament of acute pancreatitis, care for patients suffering from Ato the emergency depart- urinalysis. published in Gastroenterology. acute pancreatitis. ment with complaints of sub- A bedside ultrasound was In the U.S., acute pancreatitis is It addresses questions on the acute, right-sided flank pain negative for gallbladder pathol- a leading cause of inpatient care benefits of goal-directed fluid with migratory pain to his right ogy or nephrolithiasis; however, among gastrointestinal conditions resuscitation, early oral feeding, lower quadrant and suprapubic it revealed an abnormal appear- with more than 275,000 patients enteral vs. parenteral nutrition, the area of increasing intensity for ing liver. As further diagnostic hospitalized annually, at an aggre- routine use of prophylactic antibiot- 1 week. work up, an abdominopelvic gate cost of over $2.6 billion per ics, and routine ERCP in all patients He described his pain as computed tomography scan year. with acute pancreatitis. cramping in nature and of fluc- revealed the following images The guideline focuses on patient The guideline is accompanied tuating intensity, acutely worse (Figures A, B). The patient was care within the first 48-72 hours by a technical review, a new spot- on the day of presentation. discharged from the emergency of admission when management light (infographic) and a patient However, within 15 minutes department with scheduled fol- decisions can alter the course of companion infographic, which of waiting in the emergency low-up in the gastroenterology disease and duration of hospital- provides key points and import- department his pain subsided clinic. ization. ant information directly to acute completely. He further denied pancreatitis patients. any associated nausea, vomiting, The diagnosis is on page 22. Guideline recommendations AGA’s new guideline aims to re- [email protected]

AGA’s recommendations include:

Statement Strength of Quality of Recommendation Evidence 1A. In patients with acute pancreatitis Conditional Very low AGA suggests using goal directed recommendation quality therapy for uid management. Comment: AGA makes no recommendation whether normal saline or ringer’s lactate is used. 1B. In patients with acute pancreatitis, Conditional Very low AGA suggests against the use of recommendation quality hydroxyethyl starch (HES) uids. 2. In patients with predicted severe Conditional Low acute pancreatitis and necrotizing recommendation quality pancreatitis, AGA suggests against the use of prophylactic antibiotics. 3. In patients with acute biliary Conditional Low pancreatitis and no cholangitis, recommendation quality AGA suggests against the routine use of urgent ERCP. 4. In patients with acute pancreatitis, Strong Moderate AGA recommends early (within 24 recommendation quality hours) oral feeding as tolerated rather than keeping the patient nil per os (NPO). 5. In patients with acute pancreatitis Strong Moderate and inability to feed orally, recommendation quality AGA recommends enteral rather than parenteral nutrition. 6. In patients with predicted severe Conditional Low or necrotizing pancreatitis requiring recommendation quality enteral tube feeding, AGA suggests either nasogastric or nasoenteral route. 7. In patients with acute biliary Strong Moderate pancreatitis, AGA recommends recommendation quality cholecystectomy during the initial admission rather than following discharge. 8. In patients with acute alcoholic Strong Moderate NSTITUTE pancreatitis, AGA recommends brief recommendation quality

alcohol intervention during admission. AGA I GIHEP_13.indd 1 1/19/2018 10:23:53 AM 20 IBD AND INTESTINAL DISORDERS APRIL 2018 • GI & HEPATOLOGY NEWS

profiles met their evaluation crite- finally, independently following Analysis redened overall illness ria; it then showed them two final group discussion. Index from page 1 profiles and asked which was the Disease severity indexes were more severe case. Survey length created on a 100-point scale, and A panel of 16 experts then con- then performed to ascertain how depended on the consistency of average part-worth utility scores ducted a series of votes to deter- different clinical factors influenced participants’ responses, with those were used to determine minimum mine which attributes within each specialists’ decision making and im- lacking consistency being given and maximum scores for each at- domain would be used to assess pressions of disease severity. more tasks to complete, Dr. Siegel tribute, with zero representing the disease severity. Two sets of at- A series of questions was asked, and his colleagues reported. absence of a symptom. tributes were defined as disease with each response determining sub- Respondents completed the exer- Crohn’s disease severity was markers in Crohn’s disease and ul- sequent questions, until “ample con- cise three times: first independently largely dependent on factors relat- cerative colitis. sistency” was found in their choices. without discussion, then after dis- ed to intestinal damage, whereas A type of conjoint analysis called The exercise first had participants cussion in a group setting with an ulcerative colitis disease severity adaptive choice-based conjoint was decide which hypothetical patient automated response system, and was associated with symptoms and effects on daily life. This analysis “helps redefine overall disease severity for IBD,” the authors Disease severity indexes Exceptional were created on a 100-point scale, and average part-worth Editorial Fellowship utility scores were used Opportunity to determine minimum and maximum scores for each Gastroenterology, AGA’s flagship journal, is accepting attribute, with zero representing applications for a one-year editorial fellowship beginning in July 2018. Those entering their second the absence of a symptom. and third year of GI fellowship, as well as PhDs fewer than two years out of training, are invited to apply. wrote. Once validated, the indexes will offer “both further research Deadline for applications is Wednesday, April 18. opportunities and a practical tool by which to classify overall disease severity of patients and offer appropriate treatment without relying on Apply today at www.gastro.org/GastroFellowship. present symptoms alone,” they added. Dr. Siegel and his colleagues noted that future studies should focus

2150-310PUB_17-5 on prospective validation of the disease indexes in different patient populations, as well as conducting a conjoint analysis with patients. “We expect this work to begin to address a change in how we think about patients with IBD and how to identify those at the higher end of THE NEW GASTROENTEROLOGIST the risk spectrum so that appropriate intensive treatment can be ini- tiated and optimized in an efficient, HAS MOVED TO E-NEWSLETTER. precise, and cost-effective manner,” they concluded. The study was funded by AbbVie Now you can get the most insightful and Tillotts Pharma. The authors disclosed financial relationships early career- and fellow-focused with numerous additional pharma- updates straight to your inbox ceutical companies. with an improved online layout. [email protected] Also, be on the lookout for their monthly SOURCE: Siegel CA et al. Gut. 2018 feature articles in GI & Hepatology News. Feb;67(2):244-54.

AGA resource Learn more at www.gastro.org/thenewgastro. AGA patient education materials can help your IBD patients better understand and manage

2150-332PUB_17-3 their disease. Learn more at www.gastro.org/IBD. GIHEPNEWS.COM • APRIL 2018 IBD AND INTESTINAL DISORDERS 21

Patient education about the re- disease and ulcerative colitis. AGA Clinical Practice Update ferral to a mental health provider Clinical gaps include the need for Psych care from page 1 is difficult and requires attention to better coverage for these therapies detail and fostering a good physician- by insurance – many providers the scientific rationale and best anxieties, early-life adversity, and patient relationship. It is important are out of network or do not ac- practices associated with incorpo- functional impairment related to to help patients understand why they cept insurance, although Medicare rating brain-gut psychotherapies a patient’s digestive complaints. are being referred to a psychologist and commercial insurance plans into routine GI care. Furthermore, • Gastroenterologists should master for a gastrointestinal complaint and often cover the cost of services it presented recommendations patient-friendly language to help that their physical symptoms are not in network. Health psychologists on how to address psychological explain the brain-gut pathway and being discounted. Failure to properly can be reimbursed for health and issues and make effective referrals how this pathway can become explain the reason for referral may behavior codes for treating these in routine practice. dysregulated by any number of lead to poor follow-through and even conditions (CPTs 96150/96152), Previous studies had highlighted factors, the psychosocial risks per- lead the patient to seek care with an- but there are restrictions on which that the burden of chronic digestive petuating and maintaining factors other provider. other types of professionals can use diseases is amplified by psychoso- of GI diseases, and why the gastro- In order to foster widespread them. Ongoing research is focusing cial factors, including poor coping, enterologist is referring a patient integration of these services, re- on the cost-effectiveness of these depression, and poor social sup- to a mental health provider. search and clinical gaps need to be therapies, although some highly ef- port. Mental health professionals • Gastroenterologists should know addressed. Research gaps include fective therapies may be short term specializing in psychogastroenter- the structure and core features of the lack of prospective trials that and have a one-time total cost of ology integrate the use of brain-gut the most effective brain-gut psy- compare the relative effectiveness of $1,000-$2,000 paid out of pocket. psychotherapies into GI practice chotherapies. brain-gut psychotherapies with each There is a growing need to expand settings, which may help reduce • Gastroenterologists should estab- other and/or with that of psycho- remote, online, or digitally based health care utilization and symp- lish a direct referral and ongoing tropic medications. Other promising brain-gut therapies with more tom burden. communication pathway with one brain-gut therapies, such as mindful- trained health care providers that The article contained best prac- or two qualified mental health ness meditation or acceptance-based could offset overhead and other tice advice based on a review of the providers and assure patients approaches, lack sufficient research therapy costs. literature, including existing sys- that they will remain a part of the to be included in clinical practice. The authors state they have no tematic reviews and expert opin- care team. Limited evidence supports the effect conflicts of interest. ions. These best practices include • Gastroenterologists should fa- that psychotherapies have in accel- the following: miliarize themselves with one or erating or enhancing the efficacy [email protected] • Gastroenterologists routinely two neuromodulators that can be of pharmacologic therapies and on should assess health-related used to augment behavioral ther- improving disease course or inflam- SOURCE: Keefer L et al. Gastroenterology. quality of life, symptom-specific apies when necessary. mation in conditions such as Crohn’s 2018. doi: 10.1053/j.gastro.2018.01.045. Tofacitinib: FDA panel recommends UC indication

BY IAN LACY patients with moderate to severe UC. Patients in 5-mg group, Dr. Maller said. Frontline Medical News both studies were administered tofacitinib 10 mg Researchers also looked at a subgroup of 295 twice daily or placebo and were assessed after 8 patients who had no clinical response to tofacitinib ederal advisors to the Food and Drug Ad- weeks to judge clinical response. Patients in both 10 mg twice daily after 8 weeks and subsequently ministration on March 8 voted unanimously studies displayed notable remission rates (18.5% treated them for an additional 8 weeks as part of Fto recommend approval of an additional and 16.6%), compared with placebo, according to an open-label extension study. After the additional indication for tofacitinib (Xeljanz), this time for Eric Maller, MD, executive director of the UC devel- 8 weeks of treatment, over half (51.2%) displayed ulcerative colitis (UC). opment program at Pfizer. clinical responses and 8.6% were in remission. Members of the Gastrointestinal Drugs Advisory Patients who did not achieve remission but “This is a desperate patient population. These Committee unanimously voted to recommend two showed some clinical response (decrease in Mayo are impressive results,” stated Darrell Pardi, MD, different dosing regimens: 10 mg twice daily for score of at least 3 points) were then enrolled in the vice chair of the advisory committee and a profes- 16 weeks in patients who have not experienced a 53-week OCTAVE Sustain, where they were ran- sor of medicine at the Mayo Clinic, Rochester, Minn. therapeutic benefit after 8 weeks of domized to receive tofacitinib 10 Serious adverse events were seen in 4% of treatment, as well as 10 mg twice AGA resource mg twice daily, 5 mg twice daily, or tofacitinib-treated patients in the induction trials, daily for patients who have an Visit www.gastro.org/ placebo. compared with 6% of placebo-treated patients, ac- inadequate or loss of response to IBD for patient education During maintenance treatment, cording to Lesley Hanes, MD, medical officer with TNF-blocker therapy, based on the guides that you can share both 5-mg and 10-mg doses the FDA Center for Drug Evaluation and Research. results of several phase 3 clinical with your ulcerative coli- showed substantial treatment Adverse events appeared to be dose dependent, trials. tis patients. benefits, with 32.4% and 41.0% of with risk of deaths and malignancies (exclud- The committee rejected by a 7-8 patients achieving remission, an ing nonmelanoma skin cancer), opportunistic vote a recommendation that Pfizer, increase of 22.0% and 30.7%, com- infections, herpes zoster infection, “possible” the drug’s manufacturer, conduct a postmarketing pared with placebo, respectively. drug-induced liver injury, and cardiovascular and efficacy trial comparing a 10-mg continuous dosing As part of the maintenance study, Pfizer analyzed thromboembolic events more commonly occurring regimen with one that has a 10-mg induction dose patients with or without prior TNF-blocker failure. with the 10-mg dose, Dr. Hanes said. According to then a 5-mg twice-daily maintenance dose. This analysis revealed that patients who had pre- Dr. Pardi, “Several of these are mitigatable by der- The recommended UC indication was based on viously failed TNF-blocker therapy experienced a matologic exam or, hopefully, a vaccine.” the OCTAVE trials (N Engl J Med. 2017;376:1723- greater treatment benefit than those who had not. Several of the advisory committee members 36), including a phase 2 study; two identical While the benefit was noticeable in both dosage submitted conflict of interest waivers. Chair Jean- phase 3 induction trials (OCTAVE Induction 1 and groups, patients taking the 10-mg dose experi- Pierre Raufman, MD, and vice chair Darrell Pardi, OCTAVE Induction 2); a 53-week, phase 3 mainte- enced the greatest benefit, with a 70% increase in MD, disclosed funding from competing pharmaceu- nance trial (OCTAVE Sustain); and an open-label remission rates, 39% increase in mucosal healing, tical manufacturers. extension study. and 75% increase in steroid-free remission among The induction trials enrolled a total of 1,139 baseline remitters, compared with patients in the [email protected] 22 LIVER DISEASE APRIL 2018 • GI & HEPATOLOGY NEWS

high as 106,000 cases according to in the etiology of hepatocellular Screening will be important the exponential model. It overtook carcinoma to inform the develop- NASH from page 1 HCV infection as a cause of liver ment of screening, diagnostic, and cancer by around 2015. treatment approaches, particularly Transplantation Network, shows crease from 2.41 million in 2005 to “Despite the lack of existing given potential differences in the that the prevalence of HCV has been 42.34 million in 2025. data off of which to work, the pathology, natural history, and in steady decline since 2005 and In terms of the effect on the prev- general trends of our prediction treatment options for NASH-related that decline is forecast to continue. alence of hepatocellular carcinoma models are consistent with the and HCV-related liver cancer. From a prevalence of 3.22 million (HCC), the modeling suggested cas- documented trends of liver trans- “Histologically, NASH shares cases in 2005, researchers have es of HCV-related liver cancer were plant etiology, as well as 2010 characteristics with alcoholic liver forecasted a decline to 1.06 million predicted to peak at around 29,000 insurance data indicating nonal- disease, primarily proinflammatory cases by 2025. cases in 2015 then decline to fewer coholic fatty liver disease/NASH fat accumulation in parenchymal At the same time, even a conser- than 18,000 cases by 2025. In con- as the leading etiology associated cells, [and] key players in NASH vative linear model for the changing trast, the prevalence of HCC from with HCC,” wrote Osmanuddin progression to HCC are suggested prevalence of NASH forecast a rapid NASH is forecast to increase from Ahmed, MD, from the Rush Uni- to include genetic modifications, increase from 1.37 million cases in between 5,000 and 6,000 cases in versity Medical Center in Chicago proinflammatory high-fat and/or 2005 to 17.95 million in 2025. The 2005 to 45,000 in 2025 by the con- and his coauthors. high-fructose diets, and oxidative exponential model suggested an in- servative linear model or even as The study used liver transplant and endoplasmic cellular stresses,” data as a proxy for the prevalence they wrote. “In HCV progression to of hepatocellular carcinoma and HCC, the presence of the HCV core also took into account the natural protein may induce HCC without history of the disease. Between the prerequisite load of genetic er- 5% and 20% of untreated HCV rors normally required for cancer infections will go on to develop development, skipping or acceler- into cirrhosis, and of patients with ating some of the classic steps of HCV-related cirrhosis, around 15% cancer induction.” will develop HCC within 10 years. The authors did note that their In the case of NASH, the authors model represented a base scenario cited research suggesting that that assumed the environmental around 35% of patients go on to and genetic factors driving NASH develop progressive fibrosis, that would continue along the path of progression to cirrhosis takes current trends. around 29 years, and that the risk “Therefore, the possibility exists of progression to HCC ranged from that our models underestimate the 2.4% over 7 years to 12.8% over 3 response of the medical community years. in addressing the rising nonalco- “A higher proportion of patients holic fatty liver disease/NASH epi- with NASH develop cirrhosis, but demic.” of those who develop cirrhosis, the No funding sources or conflicts of probability of developing HCC is interest were declared. higher in patients with HCV,” the authors wrote. “In contrast, HCV [email protected] progression to HCC rarely occurs in

HINKSTOCK SOURCE: Ahmed O et al. J Clin Exp Hepa-

/T noncirrhotic patients.” The authors wrote that it was im- tology. 2018 Feb 24. doi: 10.1016/j. RAXION

E portant to explore projected trends jceh.2018.02.006. CLINICAL CHALLENGES AND IMAGES The diagnosis rare occurrence with an incidence criteria: The right hemidiaphragm sary diagnostic studies and unwar- rate of 0.25%-0.28% in the gen- must be elevated above the liver ranted surgical intervention. Answer to “What’s your eral population.2 The etiology of by the intestine, the bowel must diagnosis?” on page 12: Chilaiditi syndrome is felt to be be distended by air to illustrate References Chilaiditi syndrome congenital or acquired with pre- pseudopneumoperitoneum, and 1. Uygungul, E., Uygungul, D., Abdominal CT images display the disposing congenital abnormal- the superior margin of the liver Ayrik, C., et al. Chilaiditi sign: Chilaiditi sign, which is the ra- ities such as absent suspensory must be depressed below the level why are clinical findings more diographic term used to describe or falciform ligaments, redundant of the left hemidiaphragm.1 important in ED?. Am J Emerg interposition of the colon, usually colon, malposition of the colon, Chilaiditi syndrome is managed Med. 2015;33:733.e1-733.e2. at the hepatic flexure, with the dolichocolon, and paralysis of the conservatively with close observa- 2. Ho, M.P., Cheung, W.K., Tsai, liver and right diaphragm.1 This right diaphragm. Other risk fac- tion. Recurrent symptoms can be K.C., et al. Chilaiditi syndrome is considered an incidental radio- tors for development of Chilaiditi treated with colopexy. This syn- mimicking subdiaphragmatic graphic finding and is generally syndrome include chronic consti- drome has been known to cause free air in an elderly adult. J Am asymptomatic; however, when one pation, cirrhosis, ascites, and obe- severe complications including vol- Geriatr Soc. 2014;62:2019-21. develops clinical symptoms such sity. Men are four times as likely vulus of the cecum, splenic flexure, 3. Kang, D., Pan, A.S., Lopez, as abdominal pain, bloating or dis- as women to develop Chilaiditi or transverse colon, cecal perfora- M.A., et al. Acute abdominal tension, anorexia, constipation, or syndrome and it is more common tion, and subdiaphragmatic perfo- pain secondary to Chilaiditi nausea, it is called Chilaiditi syn- in the elderly, occurring in 1% of rated appendicitis, which all require syndrome. Case Rep Surg. drome. First described by Greek the elderly population.3 Chilaiditi surgical intervention.3 It is import- 2013;2013:756590. radiologist Demetrius Chilaiditi sign is diagnosed with radiograph- ant to recognize Chilaiditi syndrome in 1910, Chilaiditi syndrome is a ic imaging meeting the following on presentation to prevent unneces- [email protected] GIHEP_23.indd 1 3/20/2018 4:37:14 PM 24 ENDOSCOPY APRIL 2018 • GI & HEPATOLOGY NEWS Nonendoscopic nonmalignant polyp surgery increasing

BY ELI ZIMMERMAN population and from 1.1 to 3.7 per PERSPECTIVE Frontline Medical News 100,000 population, respectively. Regionally, rates of surgery were Management of complex colon polyps ate of nonendoscopic surgeries higher in the Midwest (10.8 per for nonmalignant colorectal 100,000) and the South (10.6 per n this comprehensive analysis, suspicion for malignancy. Cur- R polyps significantly increased 100,000) than in the Northeast (7.8 IPeery et al. found a rising inci- rent literature suggests that sur- from 5.9 to 9.4 per 100,000 people per 100,000) and West (7.5 per dence of surgery for nonmalignant gical removal is from 2000 to 2014, according to a 100,000). Incidence rates rose equal- colorectal polyps despite relatively recommended study in Gastroenterology. ly for both men and women. stable colorectal cancer screening less frequently These surgeries are not only as- Large urban teaching hospitals rates and with decreasing inci- by specialists sociated with a much higher risk to were found to have the largest rate dence of colorectal cancer surgery. in complex patients than endoscopic procedures, increase when data were stratified In a separate study, the authors polypectomy, but they also are significantly less by teaching status. “We had hypoth- found that 14% of patients who compared with cost effective, which confused investi- esized that surgery for nonmalig- underwent surgical resection of nonspecialists. gators as to the cause of the increase. nant colorectal polyps would be nonmalignant colorectal polyps Given this “The literature to date is clear both uncommon and declining in had a major postoperative event. study’s findings, that endoscopic resection is the pre- teaching hospitals where providers Other population-based studies health systems DR. KETWAROO ferred management of nonmalignant are more likely to be familiar with have reported similar incidence of should consider colorectal polyps,” Anne Peery, MD, a current guidelines and to have ac- surgical complications. including surgical referral rates gastroenterologist at the University cess to endoscopic mucosal resec- This report thus raises concern in their quality measures. Thus, of North Carolina at Chapel Hill, and tion,” wrote the investigators. for inappropriate surgical refer- high-quality endoscopy centers her colleagues explained. “Among The investigators first hypoth- ral. While reimbursement models would ensure that complex polyps patients who have surgery for a non- esized the increased rate seen in may play a role, many factors are are appropriately characterized and malignant colorectal polyp, 14% will teaching hospitals could be caused by involved with surgical referral. initially managed by endoscopists have at least one major short-term a higher concentration of case refer- Complex polypectomy, often us- experienced in complex polypec- postoperative event.” rals to these high-volume centers, fol- ing endoscopic mucosal resec- tomy. This is especially important Data from 1,230,458 surgeries lowing a trend of centralizing cancer tion techniques to remove large with the increasing repertoire of conducted during 2000-2014 and procedures. However, there has been polyps, is associated with higher endoscopic alternatives to surgery recorded in the Healthcare Cost no other sign that colon and rectal rates of bleeding, perforation, and that we can offer our patients. and Utilization Project National In- cancer procedures are following this incomplete resection, compared patients Sample were included in trend. with standard polypectomies. The Gyanprakash A. Ketwaroo, MD, MSc, this study. Patients who underwent Another option considered by Dr. decision to refer to surgery or to is anassistant professor, division of a nonendoscopic procedure for Peery and her colleagues was that the attempt endoscopic resection is gastroenterology and hepatology, nonmalignant polyps were predom- increased procedures may stem from based on provider experience and Baylor College of Medicine, Houston. inantly non-Hispanic white, cov- a rise in colorectal cancer screening; polyp characteristics, including He has no conflicts. ered by Medicare, from the highest however, the data indicate screenings household income range, and aged did not change from 2010 to 2015, 66 years on average. leaving investigators with few final polyps for surgery,” said Dr. Peery The investigators reported no rel- While non-Hispanic white patients guesses to go on. and fellow investigators. “Finally, evant financial disclosures. had the highest overall rate increase “It is also conceivable that increas- there is the issue of risk ... for endos- by ethnicity, rising from 5.6 to 10.5 ing production pressure and inade- copists without additional training in [email protected] per 100,000 population, rates in quate reimbursement for endoscopic advanced endoscopic resection, these non-Hispanic black and Hispanic mucosal resection may persuade risks may be perceived as too great, SOURCE: Peery A et al. Gastroenterol- patients also rose significantly, in- endoscopists to refer patients with especially when they have the option ogy. 2018 Jan 6. doi: 10.1053/j.gas- creasing from 3.5 to 5.8 per 100,000 complex nonmalignant colorectal of referring for a surgical resection.” tro.2018.01.003.

Quick Quiz Answers 2. Huang JQ et al. Meta-analysis of may range from asymptomatic to the relationship between CagA sero- symptomatic. Symptoms may in- Q1. Correct Answer: C have shown a decreased prevalence positivity and gastric cancer. Gastro- clude nausea, anorexia, abdominal of these disorders. Further studies enterology. 2003;125(6):1636-44. pain, myalgias, and fatigue. Liver Rationale are needed to verify these relation- 3. Islami F and Kamangar F. Helico- enzyme elevations are variable. The The CagA strain of Helicobacter ships, but no studies to date have bacter pylori and esophageal cancer highest mortality rates occur in the pylori has been associated with an demonstrated an increased risk of risk: A meta-analysis. Cancer Prev third trimester of pregnancy, young increased risk of gastric adenocar- esophageal carcinoma associated Res. 2008;1:329-38. children, and in those with preexist- cinoma and MALT lymphoma. Ca- with H. pylori. CagA-producing H. ing chronic liver disease. In immu- gA-producing H. pylori infection also pylori has not been associated with Q2. Correct Answer: C nocompetent hosts, HEV infection is causes more severe mucosal inflam- gastric carcinoid tumor. generally self-limited and does not mation and is associated with higher Rationale require specific treatment; therefore incidences of gastric and duodenal References This patient has contracted acute observation is the best treatment. ulcers. A protective effect of CagA+ 1. Fallone CA et al. Association of hepatitis E while traveling to Nepal, H. pylori against gastroesophageal Helicobacter pylori genotype with as evidenced by the positive hepa- Reference reflux disease, reflux esophagitis, gastroesophageal reflux disease titis E IgM. Infection is most likely 1. Kamar N et al. Hepatitis E. Lancet. Barrett’s esophagus, and esophageal and other upper gastrointesti- derived from fecal contamination of 2012;379(9835):2477-88. adenocarcinoma has been suggested, nal diseases. Am J Gastroenterol. water. Hepatitis E genotype 1 (HEV1) because some epidemiologic studies 2000;95(3):659-69. is most common in Asia. Infections [email protected] Abhinav Humar, MD Christopher Hughes, MD

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GIHEP_25.indd 1 3/15/2018 5:31:18 PM 26 GI ONCOLOGY APRIL 2018 • GI & HEPATOLOGY NEWS Colorectal cancer risk stratication enhanced by combining family history and genetic risk scores

BY TERRY L. KAMPS ing to an ongoing population-based, study in Germany, reported Korbin- Frontline Medical News case-control study of patients re- ian Weigl, PhD, and his colleagues

cruited during 2003-2010. in the journal Clinical Epidemiology / tratification of colorectal can- The research was conducted us- (doi: 10.2147/CLEP.S145636). They

cer (CRC) risk was enhanced ing data from DACHS (Colorectal included 2,363 eligible CRC patients OMMONS OMMONS C S by joint consideration of the Cancer: Chances for Prevention who were identified by 22 partic- C independent family history and ge- Through Screening), an ongoing ipating hospitals and frequency IKIMEDIA REATIVE netic risk score predictors, accord- population-based, case-control matched with respect to sex, age, W /C EPHRON OURTESY N Colorectal cancer metastasis is shown. C

and residential location to 2,198 randomly selected controls who had genome-wide association studies data. The population consisted of 40% women, and the median ages for cases and controls were 69 and 70 years, respectively. 2018 Genetic risk score was calculated AGA by genotyping 53 single-nucleotide polymorphisms reported in published literature to be associated with higher CRC risk for individuals of European descent. Seven genetic risk score groups – very low, low, Saturday, June 2, 2018 low-medium, medium, medium- 8:15 a.m.–5:30 p.m. high, high, and very high – were FROM ABSTRACT TOSunday, REALITY June 3, 2018 established according to categories generated on the basis of weighted 8:30 a.m.–12:35 p.m. risk allele distribution among con- Learn more at pgcourse.gastro.org. trols. Family history referred to CRC in first-degree and second-degree POSTGRADUATE RegisterCOURSE by April 18, 2018, and save $75. relatives. Selected potential con- 2200-080EDU_17-16 founders included age, sex, body mass index, education, hormone re- placement therapy in women, smoking, and colonoscopy history. Odds ratios with 95% confidence intervals were estimated by multiple logistic regression models that included adjustment for potential confounders. Statistical calculations examined in- WE ARE dividual and joint family history and genetic risk score associations with risk for CRC and the effect of potential confounding factors. AGA At least one colonoscopy was performed on over half the individuals in the control group, while a significant- FELLOWS ly lower number (P less than .0001) were performed on case individuals (22.1%). Family history of CRC in first-degree relatives was reported by 316 case participants (13.4%) and 214 controls (9.7%; P less than .0001). The calculated genetic risk score ranged from 20 to 48, with a substantially higher proportion of Visit www.gastro.org/fellowship cases in the higher deciles. Investigators compared the risk to learn more and apply online. for CRC in the top decile with that in Deadline: Aug. 27 the lowest and found an increased 1100-000MEM_18-2 risk of 2.9-fold (OR, 2.94) based on Continued on following page GIHEPNEWS.COM • APRIL 2018 PRACTICE MANAGEMENT 27 PRACTICE MANAGEMENT TOOLBOX: Cracking the clinician educator code in gastroenterology

BY JORDAN M. SHAPIRO, MD, MILENA GOULD ria for promotion as a CE is critical for shaping SUAREZ, MD, AND TERI LEE TURNER, MD, MPH, MED one’s career, and we recommend checking with an individual’s institution for its specific re- or gastroenterologists who enter academic quirements regarding formats for both the CV medicine, the most common career track and the teaching portfolio, which typically are Fis that of clinician educator (CE). Although available from the academic promotion com- most academic gastroenterologists are CEs, mittee. Because most fellows and faculty are their career paths vary substantially, and ex- familiar with the format of a CV, we will focus pectations for promotion can be much less on the teaching portfolio. explicit compared with those of physician sci- DR. SHAPIRO DR. GOULD SUAREZ DR. TURNER For most fellows and many faculty, the teach- entists. This delineation of different pathways ing portfolio is a new and/or less well under- in academic gastroenterology starts as early professional practice who applies theory to ed- stood entity. Unlike a CV, the teaching portfolio as the fellowship application process, before the ucation practice, engages in education scholar- presents teaching activities not only as a collection implications are understood. Furthermore, many ship, and serves as a consultant to other health or list, but also provides evidence of the influence community gastroenterologists have appoint- professionals on education issues.” the work has had on others, in a much more per- ments within academic medical centers, which Because we recognize that many community sonal way. A few tips are listed on putting together typically fall into the realm of CEs. and academic gastroenterologists spend the ma- a teaching portfolio. However, the most important A review of all gastroenterology and hepatol- jority of their education efforts teaching trainees, advice we can offer is this: one should save all evi- ogy fellowship program websites listed on the we have made every effort to ensure that the five dence of teaching including unsolicited letters and American Gastroenterological Association website recommendations listed later are equally pertinent e-mails from learners and colleagues. showed that 33 of 175 (18.8%) programs endorse to all gastroenterologists who devote any portion If your institution does not have a teaching port- distinctly different tracks, usually distinguishing of their careers to educating trainees, colleagues, folio template, we recommend using a pre-existing traditional research (i.e., basic science, epidemiolo- allied health professionals, or patients. For exam- format. Several examples from academic medicine gy, or outcomes) from clinical care of patients (i.e., ple, a CE who primarily teaches trainees still can can be found on the Internet or on MedEdPORTAL, CE or clinical scholar). One of the most common benefit from learning how to better document an open-access repository of educational content words appearing in descriptions of both tracks was their efforts, receive mentorship as an educator, provided by the Association of American Medical “clinical,” highlighting that a good CE or researcher take everyday activities and convert them into Colleges. One such tool is the Educator Portfolio is, first and foremost, a good clinician. scholarship, share teaching materials with broad- Template of the Academic Pediatric Association’s With clinical duties requiring the majority of a er audiences, and learn new teaching techniques Educational Scholars Program (available: www. CE’s time and efforts, a reasonable assumption without ever opening a book on education theory. academicpeds.org/education/educator_portfo- is that CEs are clinicians who teach trainees For community-based physicians, this can assist in lio_template.cfm). The Association of American via lectures, clinic, endoscopy, and/or inpa- obtaining recognition from academic centers for Medical Colleges Group on Education Affairs held tient rounds. Included in the category of CE are their teaching efforts. a consensus conference in 2006, from which five community clinicians who have a stake in the educational categories were defined: teaching, education of residents and fellows. Sherbino et Number 1: Maintain a current curriculum learner assessment, curriculum development, al1 defined a CE as “a clinician active in health vitae and teaching portfolio mentoring and advising, and educational leader- All CEs must have two critical instruments to ship and administration.2 These categories can document their accomplishments to their insti- serve as an arrangement for a teaching portfolio. Content from this column was originally tutions and to the field: a curriculum vitae (CV) We also recommend that you include both educa- published in the “Practice Management: The and a teaching portfolio. These items also are very tional research/scholarship and web-based educa- Road Ahead” section of Clinical Gastroenter- important when the time comes for promotion tional materials such as online learning modules, ology and Hepatology (2017;15:1828-32). because they validate one’s accomplishments, both YouTube videos, blogs, and wikis as a part of a quantitatively and qualitatively. Knowing the crite- Continued on following page

Continued from previous page to an OR of 1.86 when calculations and CRC such that individuals with included both genetic risk score were adjusted with covariates, first-degree relatives with CRC will and considering family history in genetic risk analysis adjusted for especially with previous colonosco- reach the same risk level with a first-degree relatives, thus demon- sex and age and an increased risk of pies. Using genetic risk scoring as a lower genetic risk score as those strating the enhancing effect of 3.0-fold (OR, 3.0) when all other co- calculation adjustment only slightly with a higher genetic risk score but combining the independent rela- variates except family history were changed the result (OR, 1.83). A no first-degree relatives with CRC. tionship of these two predictors. included. Comparing results against similar trend, but with lower-mag- Joint risk stratification that com- The investigators concluded from analysis with the 27 single-nucleo- nitude associations, was observed bined family history and genetic their results that, by combining the tide polymorphisms that had been with family history of CRC in sec- risk scores was compared with genetic risk scores with family his- used in previous studies indicated a ond-degree relatives. risks determined by each predictor. tory and other easy-to-collect risk sizable improvement in genetic risk A dose-response association be- As the genetic risk score increased factor information, this approach stratification as a result of increas- tween the number of risk alleles there was an observed increased “provided more accurate risk strati- ing the number of single-nucleotide and CRC risk determined by a lo- risk for individuals with first-de- fication than stratification based on polymorphisms (P value for increase gistic regression model revealed a gree relatives, second-degree each of these variables individually.” in c statistic = .003) included in the curvilinear relationship between relatives, or without family histo- The authors reported that they analysis. genetic risk score and CRC risk. At ry. Considering only genetic risk had no conflicts of interest. Risk associated with having a higher genetic risk score levels, the score, the increase in risk from the family history of CRC in a first-de- increase in CRC risk was particu- lowest to highest decile was 2.8- [email protected] gree relative was 1.5-fold (OR, 1.47) larly strong. The dose-response as- fold. In contrast, the increased risk higher in an age- and sex-adjusted sociation indicated an independent from the lowest to highest decile SOURCE: Weigl K et al. Clin Epidemiol. analysis. Risk prediction increased relationship between family history was 6.14-fold when stratification 2018;10:143-52. 28 PRACTICE MANAGEMENT APRIL 2018 • GI & HEPATOLOGY NEWS

Continued from previous page mented to improve teaching to meet overlooked or forgotten. It may be difficult to find a mentor the needs of diverse and changing when starting out as a junior faculty teaching portfolio. For each project groups of learners. Number 2: Mentors and mentees member or when changing aca- highlighted in the teaching portfolio, Both the CV and teaching portfolio Every CE needs to have a primary demic institutions. Once you have we recommend reflecting on and should be updated continually – we mentor, typically a more senior a mentor, take ownership for the writing down how the project shows recommend at least quarterly (or as faculty member with an interest in success of the relationship by man- the quantity and quality of the work. articles are published, courses are and experience with mentoring, as aging-up, by organizing all the meet- Quantity of work in the teaching taught, abstracts are presented, and well as a commitment to fostering ings, exceeding (not just meeting) portfolio refers to more than a mere so forth) – to ensure that nothing is the mentee’s professional growth. deadlines, and by communicating cataloging of published peer-reviewed articles and book chapters, courses taught, presentations given, and so forth (which should be included in the CV). Instead, it documents time spent in teaching activities, how often teaching occurs, the number and types of learners involved, and how the activity fits into a training program. Quality of work can include how innovative methods were crafted and implemented to customize teaching in creative ways to accom- A Salute to the AGA Legacy Society plish specific learning objectives. When documenting evidence of AGA g gratefullyratefully re recognizescognizes t thehe s significantignificant With a contributioncontribution ofof $5,000$5,000 oror moremore a yearyear inin quality, provide comparative mea- rolerole t thathat AGA L Legacyegacy S Societyociety m membersembers p playlay cash oror ssecuritiesecurities overover aa ffive-yearive-year pperioderiod oorr aa sures whenever possible. Quality of in e ensuringnsuring t thehe f futureuture o off gastroenterologygastroenterology gift ooff $$50,00050,000 oror mmoreore tthroughhrough a pplannedlanned ggift,ift, teaching also can be illustrated by and h hepatologyepatology a andnd i iss pleased to h honoronor t theirheir such aass a bbequest,equest, youyou ccanan jjoinoin tthehe ranksranks ooff tthehe evaluations, pretests and posttests, philanthropicphilanthropic leadership. AGA LeLegacygacy Society.Society. and as complimentary e-mails and letters from learners and other faculty members. The description of teaching activities also shows one’s John I. Allen, MD, MBA, AGAF, and Carolyn Allen Mark and Jacqueline Donowitz Anonymous (4) Cornelius Dooley and Susanne H. Hoffman-Dooley flexibility as an educator, and the Shrikant and Swati Anant David L. Earnest and Barbara S. Earnest greater the breadth of experiences, Harriette and Jeffrey Aron, MD Hashem El-Serag the better. A CE also must docu- Damian Augustyn, MD, and Caroline Augustyn, MD John Thruston Farrar, MD ment within the portfolio how the Dr. and Mrs. Richard Baerg Gianrico and Geraldine Farrugia teaching activity drew from existing Andrew and Virginia Barnes Shirley and Miles Fiterman literature and best practices and/or Mr. and Mrs. Robert C. Barnes Carol and Ronald Fogel contributed to the medical educa- Terrence Barrett, MD Dr. and Mrs. James W. Freston tion field. . Patrick Basu, MD R. Robert and Sally Funderburg The teaching portfolio templates Sumner and Susan Bell Rob and Cathy Funderburg begin with a personal statement Michael D. Bender, MD Thomas P. and Susan Gage outlining why one teaches. It is im- Henry and Joan Binder Mr. Joe Garrett Athena Blackburn Drs. John and Janet Garrett portant to include details of how Rick and Pat Boland Ralph and Patricia Giannella impact was defined or determined Marilyn and Herb Bonkovsky Mary Corretti, MD and Francis Giardiello, MD with regard to teaching endeavors, Joel V. Brill, MD Carla H. Ginsburg, MD, MPH, AGAF how the feedback from formal eval- Farron and Martin Brotman, MD Vay Liang W. Go, MD, and Frisca L. Yan-Go, MD uative processes was used to mold Michael and Josephine Camilleri George and Nancy Goldin one’s future activities as an educator, John M. Carethers, MD and Denise Carethers Cheryl MacLachlan and Fred Gorelick and what strategies will be imple- June and Don Castell Amy and Gregory Gores Cecil and Penny Chally Martin L. Greene, MD and Toby Saks Eugene B. Chang, MD, AGAF Ben A. Guider Jr., MD Take-away points William Y. Chey, MD, DSc Drs. Gail and David Hecht Sidney and Lois Cohen Charlotte Hein Estate Douglas A. Corley, MD, PhD Drs. Susan J. Henning and M. Vikram Rao 1. Think broadly about educa- Sheila Crowe, MD, AGAF, and Peter B. Ernst, DVM, PhD Alan Hofmann, MD, FRCP, AGAF, and Heli Hofmann tion scholarship: many day-to- Marcia Cruz-Correa, MD, PhD JeanMarie Houghton, MD, PhD day activities can count twice Kiron Moy Das, MD, PhD, and Kamala Das, MD Colin and Jackie Howden and be transformed into schol- Nick and Jeanne Davidson Sean E. Hunt, MD arship. 2. Start and routinely update a teaching portfolio to demon- strate the quantity and quality of education scholarship. 3. Engage in local and national opportunities to grow as a clinician educator. 4. Become familiar with different forums to share educational scholarship. 2700-000FND_18-3 GIHEPNEWS.COM • APRIL 2018 PRACTICE MANAGEMENT 29

needs and information in a way the and navigating the complexities of a teacher, educational administrator, time management, negotiation skills, mentor prefers. Rustgi and Hecht3 regulatory affairs such as institu- or researcher; determining what grantsmanship, scholarly writing, wrap up their article on mentorship tional review boards. Although many prior education projects have been and presentation skills; identify spe- with a pathway that highlights the of these tenets hold true for both successful and why; and defining cific questions regarding the type of following components for a success- clinician researchers and CEs, Farrell career goals. Step 2: identification help needed. Step 3: matchmaking: ful mentoring relationship: regular et al4 offer four steps to finding a of areas needing development: ex- determine qualities (personal and meetings, specific goals and mea- mentor for CEs, as follows. Step 1: amples may include teaching skills, professional) desired in a mentor, surable outcomes, manuscript and self-reflection and assessment: criti- curriculum innovation, evaluation/ and search for candidates with the grant writing, presentation skills, cally assessing one’s competence as assessment, educational research, help of colleagues. Step 4: engagement with a mentor: explain why you desire mentorship, career goals, current academic role(s), your perceived needs, and recognize and acknowledge appreciation for your mentor’s time and energy. One caution is to avoid having too many primary mentors. Although having clinical, research, and/or personal mentors can be helpful, having too many mentors can make it difficult to meet regularly enough to allow for the mentee–mentor relationship to grow. Instead of a network of mentors, build a web of John Inadomi and Kristine Frassett Don W. and Frances Powell minimentors to serve as consultants, Barbara H. Jung, MD, AGAF, and Gerald Tolbert, MD Robert and Deborah Proctor coaches, and accountability partners, Peter J. Kahrilas, MD, AGAF Dr. Patrick G. and Stacy S. Quinn and tap into this network as needed. Leonard E. Kane, MD, FACG, AGAF, and Tyra D. Kane, MD Jean-Pierre Raufman, MD Mentors are involved longitudinally Fasiha Kanwal Dr. and Mrs. James W. Rawles, Jr. Emmet B. Keeffe, MD, MACP, AGAF with mentees and tend to provide Jill Roberts Scott R. Ketover, MD, AGAF general career and project-specific Lynn P. and Richard H. Robinson Lawrence Kim and Nhung Van guidance, whereas coaches tend to be Joseph B. Kirsner, MD, PhD Don and Kathy Rockey involved in specific projects. Michael L. Kochman, MD, AGAF, and Mary E. Melton, MD Yvonne Romero, MD In addition to having their own Dr. and Mrs. Lawrence R. Kosinski, MD, MBA, AGAF David M. Roseman, MD mentors, CEs quickly will find oppor- Loren Laine, MD Dr. Ajoy K. Roy tunities themselves to serve as men- Nicholas F. LaRusso, MD Anil Rustgi and Poonam Sehgal tors to more junior faculty, fellows, Wayne I. Lencer Vinod K. Rustgi, MD residents, and students. Douglas Levine, MD, and Barbara Levine, PhD Seymour M. Sabesin, MD, and Marcia L. Sabesin Charles S. Lieber, MD, MACP, AGAF, and Marianne Leo- Robert and Dale Sandler Number 3: Think broadly Lieber, MD Ellen J. Scherl, MD, AGAF, and Fredric I. Harbus about scholarship David A. Lieberman, MD, AGAF Eric, Michael and Ronny Schwartz Traditionally, the definition of schol- Carolyn J. Logan Thomas J. and Vilma Serena Constance Longacher and Joseph Longacher, MD arship has been very narrow and William and Ruth Silen George F. Longstreth usually is related to the number of Alan and Louise MacKenzie Lenore R. Sleisenger and Marvin H. Sleisenger, MD publications and grants one receives. Barry and Adrienne Marshall Rhonda F. Souza, MD Beginning with Boyer’s work in Marshall and Mary Ann McCabe Stuart and Cynthia Spechler 1990, the definition of scholarship Richard W. McCallum, MD Joel and Elizabeth Stinson has expanded at academic institu- Bradford D. McKee, PharmD, and Michelle A. McKee, Reg and Margaret Strickland tions beyond the concept of tradi- PharmD June and Ian Taylor tional research.5 Medical education John G. Moore, MD G. Nicholas Verne scholarship most often is guided and Dr. Uma Murthy Tim Wang and Gregg McCarty judged by six core qualitative stan- Tom and Sally O’Meara Michael L. Weinstein, MD dards of excellence, known as “Glas- Robert H. Palmer, MD, and Jessie K. Palmer Mel, Kim, Nicki and Mel Wilcox sick’s criteria”6: clear goals, adequate Rifat Pamukcu, MD FAIMBE Patrick Y. Wong, MD preparation, appropriate methods, Stephen Jacob Pandol, MD significant results, effective presenta- Drs. Rick and Julie Peek Ginger and Taylor Wootton, MD David and Kristin Peura Drs. Gary and Elizabeth Wu tion, and reflective critique. The key C.S. Pitchumoni and Prema Pitchumoni Tadataka and Leslie Yamada to scholarship is that it builds on or Drs. Daniel and Carol Podolsky Linda Yang and Vincent W. Yang, MD, PhD adds to the field, is made public, and D. Brent Polk, MD, AGAF Dr. Yuen San Yee and Mrs. Young Yee thus available for peer-review. CE projects can be categorized As of Feb.Feb. 9, 2018. Names in bold represent sustaining members of the AGA Legacy Society 2017–2018. in many ways, but we recommend broadening the classic notions of research with which we have been indoctrinated. Golub’s7 2016 editorial in the Journal of the American Medi- Learn more at www.gastro.org/foundation cal Association, “Looking Inward and Reflecting Back: Medical Education and Journal of the American Medical Association,” highlights the range of 2700-000FND_18-3 research questions and methodolo- Continued on following page 30 PRACTICE MANAGEMENT APRIL 2018 • GI & HEPATOLOGY NEWS

Continued from previous page the results/products with Table 1. Pathways for educator development others (peer-review). Crites Level Focus Examples 8 gies, which include ethics, behavioral et al provide practical All levels American Gastroenterological Association Academy of Educators is a resource for all psychology, diversity of patient care guidelines for developing levels of clinician educators: http://www.gastro.org/about/initiatives/aga- and the workforce, medical education education research ques- academy-of-educators research, quality and value of care, tions, designing and imple- Beginner Improving teaching Book: Clinician-Educator Handbook: https://media.bcm.edu/documents/2014/84/ skills in the clinical clinicianedhandbook.pdf well-being of trainees and faculty, menting scholarly activities, setting Online modules (particularly feedback, 1-minute preceptor, and evaluating your and health informatics. If one breaks and interpreting the scope student): https://www.med-ed.virginia.edu/courses/fm/precept/index.htm down daily tasks, countless oppor- and impact of education Live courses or webinars: faculty development GME Ichan School of Medicine at Mount Sinai: https://www.youtube.com/channel/UCI23qEame4hvIWPI3Mi8dbA tunities for scholarly projects will scholarship. Grand rounds, workshops, or educational seminars at home institution or regional/ emerge. One need look no further In addition, reaching be- national meeting than the opportunities for quality im- yond one’s department to Intermediate Building your Essential Skills in Medical Education online course: https://amee.org/amee- provement research that avail them- other departments, as well teaching repertoire initiatives/esme-courses/amee-esme-online-courses/esme-online by learning about Harvard Macy Institute live courses: http://www.harvardmacy.org/ selves daily, with examples ranging as participating in educa- the science of Coursera online course (i.e., Instructional methods in Health Professions Education): from reducing variation in cirrhosis tional scholarly activities on medical education https://www.coursera.org/learn/instructional-methods-education care to improving adenoma detection regional and national levels, Longitudinal teacher training programs at home institution (i.e., Master Teacher Fellowship) rates. Quality improvement is an is important as one’s career Advanced Applying the Certicate or degree programs in medical education — current listing can be found at: important method of scholarship for progresses. Well-connect- science of http://www.aacom.org/one/profdev/fac-dev/degree-programs both academic and community-based ed and diverse networks education to the The Association of Medical Educationin Europe MedEdWorld Webinars: physicians, which also can contribute are information highways clinical teaching http://www.amee.org/amee-initiatives/mededworld/webinars setting and Resources for medical education research and scholarship: http://omerad.msu. toward Part IV of Maintenance of Cer- by which one’s work can obtaining an edu/chmeducator/meded_research_scholarship.html tification requirements. CEs also can be amplified to achieve a advanced degree Association of American Medical Colleges Medical Education Research Certicate engage in educational scholarship greater impact, and from program: https://www.aamc.org/members/gea/merc/ other than research by using these which many opportunities Note: Developed by Dr. Turner. same principles. To transform your will be shared. teaching into scholarship you should fellows; faculty; other health pro- focused on wider changes in the examine the activities you perform Number 4: Share broadly fessions; or even patients and the organization or delivery of care at- or a problem that needs to be solved, Scholarship activities of both aca- community. Knowing who will be the tributable to an educational program. apply information or a solution based demic and community-based CEs recipients or end-users can help to Level 4b: focused on improvements on best practices or what is known can target many audiences, includ- identify which types of projects may in the health and well-being of pa- from the literature, and then share ing medical students, residents, and be most rewarding and make the tients as a direct result of an educa- greatest impact. Consider sharing cur- tion initiative. ricula, evaluation tools, and other ed- Similar to more traditional clinical ucational products with colleagues at research, education research needs to CLASSIFIEDS other institutions who ask for them. be performed in a scholarly fashion Request acknowledgment for the and shared with a wider audience. Also available at MedJobNetwork.com development of the materials and ask In addition to submitting research PROFESSIONAL OPPORTUNITIES for written feedback on how these to gastroenterology journals (e.g., products are being used. Gastroenterology’s Mentoring, Ed- One education model used to ucation, and Training Corner), edu- assess the impact and target of cation research can be submitted to WHERE A LANDSCAPE OF education interventions is known education journals such as the Asso- as Kirkpatrick’s9 hierarchy, which ciation of American Medical Colleges’ OPPORTUNITIES AWAITS A traditionally included the follow- Academic Medicine, the Association ing four levels: reaction (level 1), for the Study of Medical Education’s GASTROENTEROLOGIST learning (level 2), behavior (level 3), Medical Education, the Accredita- and results (level 4). The model has tion Council for Graduate Medical Gundersen Health System in La Crosse, Wisconsin been adapted by the British Medical Education’s Journal of Graduate is seeking a BC/BE Gastroenterologist to join its Journal’s Best Evidence in Medical Medical Education, or the European established medical team. Education collaboration to medical Association for Medical Education Practice in our state-of-the-art Endoscopy Center education with the following modifi- in Europe’s Medical Teacher; online and modern outpatient clinic. Outreach services are cations in levels as follows.9,10 Level education warehouses such as Med- provided at our satellite clinics located within an 1: participation: focused on learners’ EdPORTAL (www.mededportal.org) easy drive from La Crosse. In addition, you will have opportunities for clinical research and will be views of the learning experience or MERLOT (www.merlot.org); and actively involved in teaching our Surgical, including content, presentation, and national conferences as workshops. Transitional, and Internal Medicine residents. teaching methods. Level 2a: mod- Also, keep in mind that opportunities You’ll join a physician-led, not-for-pro t health ification of attitudes/perceptions: arise on a regular basis to share edu- system with a top-ranked teaching hospital and focused on changes in attitudes or cational videos or images in forums one of the largest multi-specialty group practices perceptions between participant such as the American Society for with about 700 physicians and associate medical groups toward the intervention. Lev- Gastrointestinal Endoscopy’s video sta. Visit gundersenhealth.org/MedCareers el 2b: modification of knowledge/ journal VideoGIE, The American Send CV to Kalah Haug skills: for knowledge, focused on the Journal of Gastroenterology’s video of Medical Sta Recruitment acquisition of concepts, procedures, the month, and Clinical Gastroenter- Gundersen Health System and principles; for skills, focused on ology and Hepatology’s Images of the [email protected] or call (608)775-1005. the acquisition of problem solving, Month. psychomotor, and social skills. Level 3: behavioral change: focused on the Number 5: Ongoing transfer of learning to the workplace professional development

EEO/AA/Veterans/Disabilities or willingness of learners to apply Continuing Medical Education is a new knowledge and skills. Level 4a: standard requirement to maintain change in organizational practice: Continued on following page GIHEPNEWS.COM • APRIL 2018 PRACTICE MANAGEMENT 31

ductory guide: AMEE guide no. 89. Med Continued from previous page Teach. 2014;36:657-74. Turner is an associate professor of 9. Kirkpatrick, D.L. Evaluation of training. Dr. Shapiro is a gastroenterology pediatrics, vice chair of education, an active medical license because it In: R. Craig, L. Bittel (Eds.) Training and fellow in the department of medi- associate program director for house shows ongoing efforts to remain up development handbook. McGraw-Hill, cine, section of gastroenterology; Dr. staff education, section of academic to date with changes in medicine. New York; 1967: 87-112. Gould Suarez is an associate profes- general pediatrics, and director for 10. Littlewood, S., Ypinazar, V., Margol- Similar opportunities exist with is, S.A., et al. Early practical experience sor in the department of medicine, research, innovation, and scholar- respect to further development as and the social responsiveness of clini- section of gastroenterology and ship, Baylor College of Medicine, an educator. Given the multitude of cal education: systematic review. BMJ. associate program director of the Houston. The authors disclose no manners in which these opportuni- 2005;331:387-91. gastroenterology fellowship; and Dr. conflicts. ties can be divided, we have compiled recommendations for resources on educational scholarship based on level of experience and desired level of engagement (Table 1).

Summary The framework provided should help guide the gastroenterologist on the path of becoming an effective CE in gastroenterology. The success of the future of medical education and our careers requires not only that every CE be productive, but also that each one brings a unique passion to work each day to share. The authors would like to thank all those CEs who contributed to our education, and look forward to learning from you in the future.

References 1. Sherbino, J., Frank, J.R., Snell, L. Defin- ing the key roles and competencies of the clinician-educator of the 21st century: a national mixed-methods study. Acad Med. 2014;89:783-9. 2. Simpson, D., Fincher, R.M., Hafler, J.P., et al. Advancing educators and education by defining the components and evidence associated with educational scholarship. Med Educ. 2007;41:1002-9. 3. Rustgi, A.K. Hecht, G.A. Mentorship in academic medicine. Gastroenterology. 2011;141:789-92. 4. Farrell, S.E., Digioia, N.M., Broderick, K.B., et al. Mentoring for clinician-educators. Acad Emerg Med. 2004;11:1346-50. 5. Boyer, E.L. Scholarship reconsidered: priorities of the professoriate. Carne- gie Foundation for the Advancement of Teaching, Princeton, NJ; 1990. 6. Glassick, C.E., Taylor-Huber, M., Maeroff, G.I., et al. Scholarship assessed: evaluation of the professoriate. Jossey-Bass, San Francisco; 1997. 7. Golub, R.M. Looking inward and reflecting back medical education and JAMA. JAMA. 2016;316:2200-3. 8. Crites, G.E., Gaines, J.K., Cottrell, S., et al. Medical education scholarship: an intro-

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