AGA Clinical Practice Update

2007-10-Year Anniversary-2017 VOL. 11 NO. 2 FEBRUARY 2017

21st Century Cures INSIDE IBD AND INTESTINAL Act: $500 million DISORDERS Red meat tied to diverticulitis for FDA reform In men especially, higher fresh red meat consumption may BY GREGORY TWACHTMAN Obama said when signing increase risk. • 21

hanna Frontline Medical News the law. “I started the 2016 ENDOSCOPY,

ahil K State of the Union ad- s .

r he 21st Century Cures dress by saying we might PANCREAS & BILIARY Act – bipartisan leg- be able to surprise some TRACT islation to support cynics and deliver bipar-

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C medical research, reform tisan action on the opioid Dr. Sahil Khanna and coauthors recommend careful monitoring and the Food and Drug Admin- epidemic. And in that hypertriglyceridemia treatment of C. difficilein IBD, as each worsens the other. istration, address the opi- same speech, I put [Vice ups pancreatitis risk oid epidemic, and improve President] Joe [Biden] in The triglyceride access to mental health charge of Mission Control threshold is not known • AGA Clinical care – has passed both on a new cancer moon- 24 Houses of Congress and shot. And today, with the been signed by President 21st Century Cures Act, AGA Clinical Practice Practice Update: Obama last month before we are making good on Update: Commentary leaving office. both of those efforts. We Endoscope reprocessing C. difficile “It is wonderful to see are bringing to reality the guidelines are an in IBD how well Democrats and possibility of new break- improvement. • 25 Republicans in the clos- throughs to some of the BY AMY KARON his associates (Clin Gastroen- ing days of this Congress greatest health challenges LIVER DISEASE Frontline Medical News terol Hepatol. 2016 Feb. doi: came together around a of our time.” AGA Guideline 10.1016/j.cgh.2016.10.024). common cause, and I think A pared-down version Expert suggests how to nflammatory bowel dis- Clinicians should also test for it indicates the power of of the 21st Century Cures manage acute liver ease (IBD) increases the recurrent CDI if symptoms of this issue and how deeply Act passed the House Nov. failure. • 29 Irisk and severity of Clos- colitis persist or return after it touches every family 30 by an overwhelming tridium difficile infection antibiotic therapy for CDI, across America,” President See Cures Act · page 4 (CDI) while CDI tends to they emphasized. complicate and worsen the CDIs are on the rise and clinical course of IBD, experts now cause about 29,000 Docs may lose income with ACA repeal note in a Clinical Practice deaths annually in the Update. United States, surpassing BY GREGORY TWACHTMAN January 2016 budget rec- and the insurance mar- Thus, it is crucial that clini- the combined death count Frontline Medical News onciliation bill as the basis ketplace premium tax cians pursue stool testing for from methicillin-resistant for their projections esti- credits and cost-sharing toxigenic C. difficile infection Staphylococcus aureus n expected partial re- mate that the partial repeal reductions. In addition, whenever a patient with and multidrug resistant Apeal of the Affordable could result in as many as there would be a surge in IBD presents with a colitis gram-negative bacteria. Care Act would hit physi- 29.8 million Americans los- uncompensated care. flare, regardless of recent Reasons for this concerning cians’ bottom line, according coverage through the “The coverage losses antibiotic history, wrote Sahil trend include rising antibi- ing to a new analysis from elimination of the Medicaid would in turn decrease rev- Khanna, MBBS, of the Mayo otic use, population aging, the Urban Institute. expansion, the individual enues for providers of all

Clinic, Rochester, Minn., and See AGA CPU · page 20 Analysts using the vetoed and employer mandates, See ACA repeal · page 2

Plainview, NY 11803-1709 NY Plainview,

Lebanon Jct. KY Jct. Lebanon

Suite 2, 2, Suite Permit No. 384 No. Permit

PAID

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Presorted Standard Presorted CHANGE SERVICE REQUESTED SERVICE CHANGE GI & Hepatology News Hepatology & GI 2 NEWS FEBRUARY 2017 • GI & HEPATOLOGY NEWS Uncompensated care at issue LETTER FROM THE EDITOR: ACA repeal from page 1 New President, but types,” the report states. “Providers’ for the remainder,” the report notes. variable costs would also decrease, “If federal, state, and local govern- but their fixed costs would not.” ments do not allocate more funding GI & Hepatology News’ The Urban Institute estimates that for this care, the financial burden spending by insurers (public and would fall on health care providers. mission stays the same private) and households on health Large increases in unmet need for care delivered to the nonelderly the uninsured are likely because would decrease by $145.8 billion in the additional costs would require a y the time this issue is genetic causes for colorectal 2019 and $1.7 trillion between 2019 fourfold increase in provider funding published, we will have cancer. In the Practice Manage- and 2028. of uncompensated care from current Bseen the inauguration of ment Toolbox, Xavier Llor, MD, levels.” Donald J. Trump as the 45th PhD, outlines steps to develop a Congressional Republicans plan to president of the United States, coordinated ‘If federal, state, and local use the budget reconciliation process and we will have begun to colorectal to partially repeal the revenue-gen- understand the process and cancer ge- governments do not allocate more erating aspects of the ACA, a process implications of repealing and netics pro- funding for [uncompensated] that allows the repeal to go through replacing the Affordable Care gram, based with a simple majority in the Senate. Act. We have provided you with on his work care, the financial burden would However, repeal of the health care information about potential at Yale Uni- fall on health care providers.’ reform law’s other parts would re- financial losses under ACA re- versity. quire at least 60 votes in the Senate, peal and highlighted the new Finally, requiring at least eight Democrats to 21st Century Cures Act. I hope you side with the Republican majority, Our articles span the spec- DR. ALLEN again enjoy The increase in the uninsured assuming none in the majority go trum of current clinical issues our latest would cause a spike of $88 billion against the party. from endoscope cleaning to Flashback column. This month in uncompensated care ($26.4 bil- The Trump administration has propofol safety. This month we we look back at an important lion in hospital care, $11.9 billion in signaled that it plans to maintain also feature articles highlight- article from 2008, our second physician office care, $33.6 billion in certain aspects of the ACA, including AGA commentaries and year of publication. As this other services, and $18.0 billion in ing the ability for parents to cover guidelines. AGA has produced a year continues, we will try to prescription drugs), reaching $1.1 children up to age 26 and the ban Clinical Practice Update based keep you abreast of the rapidly trillion between 2019 and 2028. At on denial of coverage for preexisting on the Multi-Society Task Force changing political and policy the same time, federal funding for conditions. guideline on scope reprocess- landscape, while providing uncompensated care would increase Research for the report was funding and a guideline concerning updates on the latest scientific no more than $3.2 billion in 2019 ed by the Robert Wood Johnson management of acute liver research. and no more than $35 billion from Foundation. failure. 2019 to 2028, analysts state. Several articles highlight John I. Allen MD, MBA, AGAF “There is no clear source of funding [email protected] the importance of recognizing Editor in Chief

Editor in ChiEf Gi & hEpAtoloGy nEws is the official newspaper of the American Gastroenterological frontlinE mEdiCAl CommuniCAtions soCiEty pArtnErs John I. Allen, MD, MBA, AGAF Association (AGA) Institute and provides the gastroenterologist with timely and VP/Group Publisher; Director, FMC Society Partners Mark Branca relevant news and commentary about clinical developments and about the impact AssoCiAtE Editors Mary Jo M. Dales of health care policy. Content for Gi & hEpAtoloGy nEws is developed through a Editor in Chief Megan A. Adams, MD, JD, MSc partnership of the newspaper’s medical board of editors (Editor in Chief and Associate Executive Editors Denise Fulton, Kathy Scarbeck Ziad Gellad, MD, MPH Editors), Frontline Medical Communications Inc. and the AGA Institute Staff. “News Managing Editor Lora T. McGlade Kim L. Isaacs, MD, PhD from the AGA” is provided exclusively by the AGA, AGA Institute, and AGA Research Creative Director Louise A. Koenig Bryson Katona, MD, PhD Foundation. All content is reviewed by the medical board of editors for accuracy, Director, Production/Manufacturing Rebecca Slebodnik Gyanprakash A. Ketwaroo, MD, MSc timeliness, and pertinence. To add clarity and context to important developments Larry R. Kosinski, MD, MBA in the field, select content is reviewed by and commented on by external experts National Account Manager Artie Krivopal, 973-206-2326, Sonia S. Kupfer, MD selected by the board of editors. cell 973-202-5402, [email protected] Wajahat Mehal, MD, PhD Senior Director of Classified Sales Tim LaPella, 484-921-5001, The ideas and opinions expressed in Gi & hEpAtoloGy nEws do not necessarily [email protected] Editors EmEritus reflect those of the AGA Institute or the Publisher. The AGA Institute and Frontline Advertising Offices 7 Century Drive, Suite 302, Parsippany, Colin W. Howden, MD, AGAF Medical Communications Inc. will not assume responsibility for damages, loss, NJ 07054-4609 973-206-3434, fax 973-206-9378 Charles J. Lightdale, MD, AGAF or claims of any kind arising from or related to the information contained in this AGA institutE stAff publication, including any claims related to the products, drugs, or services mentioned FRONTLINE MEDICAL COMMUNICATIONS herein. Advertisements do not constitute endorsement of products on the part of the Managing Editor Brook A. Simpson Chairman Stephen Stoneburn Vice President, Human Resources AGA Institute or Frontline Medical Communications Inc. President, Digital & CFO & Facility Operations Special Content Editor Lindsey M. Brounstein Douglas E. Grose Carolyn Caccavelli Senior Publications Coordinator Jillian L. Schweitzer POSTMASTER Send changes of address (with old mailing President, CEO Alan J. Imhoff Vice President, Marketing & Customer Vice President of Publications Erin C. Landis label) to GI & Hepatology News, Subscription Service, 151 President, Custom Solutions Advocacy Jim McDonough JoAnn Wahl Vice President, Sales Mike Guire offiCErs of thE AGA institutE Fairchild Ave., Suite 2, Plainview, NY 11803-1709. Senior Vice President, Finance Vice President, Society Partners President Timothy C. Wang, MD, AGAF The AGA Institute headquarters is located at 4930 Del Ray Steven J. Resnick Mark Branca President-Elect Sheila E. Crowe, MD, AGAF Avenue, Bethesda, MD 20814, [email protected]. Vice President, Operations Corporate Director, Research & Vice President David A. Lieberman, MD, AGAF Editorial Offices 2275 Research Blvd, Suite 400, Rockville, MD 20850, Jim Chicca Communications Lori Raskin Vice President, Audience Secretary/Treasurer Francis M. Giardiello, MD, AGAF 240-221-2400, fax 240-221-2548 In affiliation with Global Academy Development Donna Sickles Gi & hEpAtoloGy nEws for Medical Education, LLC ©2017 by the AGA Institute. All rights reserved. No part of this (ISSN 1934-3450) is published monthly for Vice President, Custom Programs Vice President, Medical Education publication may be reproduced or transmitted in any form or by any $230.00 per year by Frontline Medical Communications Inc., Scan this QR Carol Nathan 7 Century Drive, Suite 302, Parsippany, NJ 07054-4609. Code to visit & Conferences means, electronic or mechanical, including photocopy, recording, or any Vice President, Custom Solutions Sylvia H. Reitman, MBA Phone 973-206-3434, fax 973-206-9378 gihepnews.com Wendy Raupers information storage and retrieval system, without permission in writing Vice President, Events David J. from the publisher. Vice President, eBusiness Small, MBA Development Lee Schweizer # 1 MOST PRESCRIBED, BRANDED BOWEL PREP KIT1

FIVE-STAR EFF1CACY WITH SUPREP ¨

Distinctive results in all colon segments >90% no residual stool in all colon segments compared to Standard 4-Liter Prep2*†‡ • These results were statistically significant in the cecum (P=.010)2*§ • Significantly more patients in the SUPREP group had no residual fluid in 4 out of 5 colon segments2*‡ Help meet the Gastroenterology Quality Improvement Consortium (GIQuIC) benchmark for 85% quality cleansing3 with the split-dose effi cacy of SUPREP Bowel Prep Kit.4

*This clinical trial was not included in the product labeling. †Standard 4-Liter Prep [sulfate-free polyethylene glycol (PEG) electrolyte lavage solution]. ‡Based on investigator grading. §Statistically signiﬁ cant difference. References: 1. IMS Health, NPA Weekly, July 2016. 2. Rex DK, Di Palma 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. Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Gastrointest Endosc. 2015;81(1):31-53. 4. SUPREP Bowel Prep Kit [package insert]. Braintree, MA: Braintree Laboratories, Inc; 2012.

GIHEP_3.indd 1 1/25/2017 12:39:40 PM 4 NEWS FEBRUARY 2017 • GI & HEPATOLOGY NEWS

from $9.3 billion to $4.8 billion devices, streamlined review for Funding reduced for approval over a 10-year period. Further, drug/device combinations, and Cures Act from page 1 those funds are not guaranteed increased patient involvement in but will need to be appropriated the drug approval process, with 392-26 vote, gaining more support of Senate approval, funding for through the federal budget pro- $500 million to implement the on the House floor than did a ver- key biomedical research efforts cess. Key provisions of the bill reforms. sion of the legislation that passed – the BRAIN Initiative, the Can- (H.R. 34) include: • $4.8 billion over a 10-year peri- the House in 2015. For that addi- cer Moonshot, and the Precision • FDA reforms, including expedit- od for key biomedical research tional support and for assurance Medicine Initiative – was reduced ed review for certain medical efforts including the BRAIN Initiative, the Cancer Moonshot, and the Precision Medicine Ini- tiative. • $1 billion in grants to states over a 2-year period to help supplement opioid abuse prevention and treatment activities. • Provisions to improve the in- teroperability of EHRs. • Provisions to improve the treatment of serious mental illness.

IMPORTANT SAFETY INFORMATION 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. 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 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 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 and ingestion of additional water as recommended is important to patient tolerance. hitehouse . gov W ® BRIEF SUMMARY: Before prescribing, please see full Prescribing Information and Medication Guide for SUPREP Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) President Obama signs the 21st Century 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 Cures Act. in the following conditions: gastrointestinal (GI) obstruction, bowel perforation, toxic colitis and toxic megacolon, gastric retention, ileus, known allergies to components of the kit. WARNINGS AND PRECAUTIONS: 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, 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 The FDA funding is designed to 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 help the agency speed up the drug electrolytes. Pre-dose and post-colonoscopy ECG’s should be considered in patients at increased risk of serious cardiac arrhythmias. Use can cause temporary elevations in uric acid. Uric acid fluctuations in approval process, focusing on iden- 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 tifying biomarkers and developing requiring hospitalization. Patients with impaired water handling who experience severe vomiting should be closely monitored including measurement of electrolytes. Advise all patients to hydrate adequately targeted drugs for rare diseases. It before, during, and after use. Each bottle must be diluted with water to a final volume of 16 ounces and ingestion of additional water as recommended is important to patient tolerance.Pregnancy: also reauthorizes the pediatric rare Pregnancy Category C. Animal reproduction studies have not been conducted. It is not known whether this product can cause fetal harm or can affect reproductive capacity. Pediatric Use: Safety and disease priority review voucher effectiveness in pediatric patients has not been established. Geriatric 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%) program, requires drug companies were 75 years of age or older. No overall differences in safety or effectiveness of SUPREP Bowel Prep Kit administered as a split-dose (2-day) regimen were observed between geriatric patients and younger to have a publicly accessible com- 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 passionate use policy for drugs adverse reactions (>2%) are overall discomfort, abdominal distention, abdominal pain, nausea, vomiting and headache. Oral Administration: Split-Dose (Two-Day) Regimen: Early in the evening treating serious or life-threatening prior to the colonoscopy: Pour the contents of one bottle of SUPREP Bowel Prep Kit into the mixing container provided. Fill the container with water to the 16 ounce fill line, and drink the entire amount. Drink two additional containers filled to the 16 ounce line with water over the next hour. Consume only a light breakfast or have only clear liquids on the day before colonoscopy.Day of conditions, and provides flexibility Colonoscopy (10 to 12 hours after the evening dose): Pour the contents of the second SUPREP Bowel Prep Kit into the mixing container provided. Fill the container with water to the 16 ounce to get new antimicrobial drugs to fill line, and drink the entire amount. Drink two additional containers filled to the 16 ounce line with water over the next hour. Complete all SUPREP Bowel Prep Kit and required water at least two hours market quickly. 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 Changes in the drug approval Braintree Laboratories, Inc. Braintree, MA 02185. process were contentious during debate on the House floor. “In its attempt to speed up the drug and device approval process, this legislation neglects the very people whom clinical trials are meant to help, that is, the patients,” Rep. Rosa DeLauro (D-Conn.) said. For additional information, please call 1-800-874-6756 or visit www.suprepkit.com “Rather than protect those who rely on the health care system, it reduces the already weak regu- ©2016 Braintree Laboratories, Inc. All rights reserved. 16-00927 September 2016 lation on medical devices, allows drugs with only limited evidence of the drug’s safety and efficacy, and rushes the use of new and unprov- en antibiotics.” Other legislators expressed dis- appointment at the bill’s mental Continued on following page GIHEPNEWS.COM • FEBRUARY 2017 NEWS 5

Continued from previous page a great first step toward greater and Mike Lee (R-Utah), with most Sen. Sanders said on the Senate collaboration and communication objecting that the legislation did floor. “How can we talk about a bill health care provisions. Rep. Joseph among federal agencies and public not address key issues in the need dealing with the pharmaceutical Kennedy III (D-Mass.) said that his stakeholders.” to find cures for major diseases. industry without addressing the ele- “real concerns with the legislation In the Senate, only five mem- “The most important prescription phant in the room, which is the fact lie with the mental health reform bers voted against the legislation: drug–related crisis facing our coun- that we pay the highest prices in the proposals, which don’t go nearly Sens. Elizabeth Warren (D-Mass.), try right now is the skyrocketing world for medicine?” far enough. Mental health parity Bernie Sanders (I-Vt.), Ron Wyden price of prescription drugs. This bill is already the law, thanks to the (D-Ore.), Jeff Merkley (D-Ore.), does not even deal with that issue,” [email protected] Mental Health Parity and Addiction Equity Act and the Affordable Care Act, but each study we read, Mr. Speaker, and each story we hear proves that insurance companies are skirting those rules. “We need enforcement and transparency today,” Rep. Kennedy continued. “We need random au- dits before there have been viola- tions, not after. We need insurers to publicly disclose the rates and reasons for denials in a way that patients and their families can understand, not in a way that mental health advocates can’t even obtain. We need to increase Medicaid re- imbursements in order to expand access to care, not to reduce them or roll back expansion.” 21st Century Cures also con- tains health IT–related provisions, mostly aimed at improving the in- teroperability of electronic health records. It also reduces the documentation burden on providers and establishes the authority for the Health & Human Services Of- fice of Inspector General to penal- ize those engaged in information blocking between EHRs. The bill also increases the transparency around Medicare local coverage decisions and exempts certain transfers of value from reporting requirements related to continuing education. It sets reimbursement for Medicare Part B drugs infused through durable medical equipment at 106% of the average sales price. Other provisions include creation of a National Institutes of Health program to support new researchers; funds to accelerate improved methods for prevention, diagnosis, and treatment of tick- borne diseases; the development of a national neurologic condition surveillance system; and the establishment of a task force on research specific to pregnant and breastfeeding women. “More women with chronic diseases are becoming pregnant, yet safe and effective medications to manage these ongoing conditions throughout their pregnancy and beyond are needed,” Mary Norton, MD, president of the Society for Maternal-Fetal Medicine, said in a statement. “This legislation is 6 NEWS FEBRUARY 2017 • GI & HEPATOLOGY NEWS

FLASHBACK TO APRIL 2008 2007-10-Year Anniversary-2017

he April 2008 issue of GI & country to grapple with the clinical VOL. 2 • NO. 4 • APRIL 2008 Hepatology News (GIHN) fea- implications of SSAs. Roy’s article &HEPATOLOGY NEWS tured an article by Roy M. was accompanied by an excellent GI OFFICIAL NEWSPAPER OF THE AGA INSTITUTE T INSIDE Telaprevir Regimen Soetikno, MD, MS, FASGE and his commentary by Jerome D. Waye, MD, Upper GI Tract Reduced Viral Load Are PET Scans

S YSTEM Reliable?

colleagues from the Palo Alto VA FASGE, who emphasized the impor- C ARE A negative scan after In Chronic Hep C esophageal chemoradiation EALTH

H does not mean surgery is Therapy included ribavirin, peginterferon. unnecessary. • 8 A LT O

ALO Liver, Pancreas & Medical Center in California. They tance of a slow withdrawal time and BY MICHELE G. France, presented the 36-week SULLIVAN results of the Investigation of Biliary Tract Elsevier Global Medical News HCV Protease Inhibition for Vi- Systemic

/VA P R EVELL /VA ral Eradication (PROVE 2) B OSTON — Telaprevir, an in- study. Conducted in four Euro- Therapies HUCK drew our attention to nonpolypoid meticulous visual technique during C vestigational protease inhibitor, pean countries, PROVE 2 is Sorafenib extended survival of “What you don’t know or don’t believe in, you don’t seek,” said has the potential to quickly re- sponsored by Vertex Pharma- hepatocellular carcinoma Dr. Roy M. Soetikno, lead investigator in the Flat Lesion Study. duce viral load in patients with ceuticals Inc., which makes the patients in two studies. • 12 chronic hepatitis C infection, drug and funded the research. according to the interim results The placebo-controlled trial From the AGA Institute (flat) colonic lesions in an article colonoscopy. Key points in the JAMA of a phase II study presented at randomized 322 patients with Do Nonpolypoid Lesions the annual meeting of the treatment-naive genotype 1 New Consensus American Association for the chronic hepatitis C infection Guidelines Predict Colorectal Ca? Study of Liver Diseases. into four groups: But the contribution of rib- Ǡ Group A: standard-of-care The AGA Institute supports the from JAMA (2008;299:1027-35). article were a) prevalence of flat le- BY HEIDI SPLETE particular are more likely to be avirin to achieving a sustained treatment (peginterferon 180 CRC screening guidelines that Elsevier Global Medical News cancerous, but few studies have virologic response (SVR) can’t mcg weekly plus 1,000-1,200 mg make cancer prevention the examined NP-CRNs as predic- be underestimated, said Dr. ribavirin/day and placebo in new primary goal. • 15 ubtle nonpolypoid colorec- tors of colorectal cancer. Christophe Hezode, lead inves- place of telaprevir for 48 weeks). tal neoplasms were more In this cross-sectional study, tigator. “In treatment arms con- Ǡ Group B: 750 mg telaprevir Lower GI Tract Coincidentally, the week before this sions was about 9% in a screening Spredictive of colorectal can- Dr. Roy M. Soetikno of the Vet- taining ribavirin, the viral break- every 8 hours and the weekly cer than were the more obvious erans Affairs Palo Alto (Calif.) through rate was very low, only peginterferon for 12 weeks, fol- Pain Perception polypoid neoplasms, according Health Care System and his col- 1%-2%, while in the arm that lowed by another 12 weeks of Differs in IBS to investigators in a study of leagues reviewed the character- did not contain ribavirin, the peginterferon and ribavirin. Brain responses to anticipated 1,819 adult patients. istics of colorectal neoplasms in rate was 24%. This shows the Ǡ Group C: 750 mg telaprevir pain and pain itself were article appeared, I was sitting with population, b) small flat polyps can Polypoid neoplasms are easier asymptomatic and symptomatic very profound antiviral activity every 8 hours, plus peginterfer- altered in irritable bowel to detect during a colonoscopy, adults (JAMA 2008;299:1027-35). of ribavirin.” on and ribavirin for 12 weeks. syndrome patients. • 16 and they are routinely removed The study population included Dr. Hezode, of Henri Mon- as a strategy to prevent colorec- 616 asymptomatic patients (called dor University Hospital, Créteil, See Viral Load • page 2 Roy in Kyoto at a conference of inter- harbor advanced histologic changes tal cancer. By contrast, nonpol- screening patients), 654 asympto- ypoid colorectal neoplasms (NP- matic patients with a personal or CRNs) are usually flat or slightly family history of colorectal neo- depressed in shape, which makes plasms (called surveillance pa- Early Data: Aspirin Looks Safe for Barrett’s them harder to distinguish from tients), and 549 symptomatic pa- national experts focused on flat co- including cancers, and c) many phy- the surrounding normal mucosa. tients. The patients underwent BY FRAN LOWRY AspECT is an ambitious, 10- The investigators are also try- Previous studies have shown Elsevier Global Medical News year clinical trial being conduct- ing to determine whether this that the depressed NP-CRNs in See Prediction • page 5 ed in the United Kingdom. The therapy will prevent or reduce O RLANDO — Findings from investigators are still recruiting the incidence of myocardial in- the Aspirin Esomeprazole to meet their goal of 2,500 pa- farction. lonic lesions. The Japanese definitions sicians who perform colonoscopy Prevalence of Chemoprevention Trial indicate tients. The United Kingdom is fertile Nonpolypoid Colorectal Neoplasms that therapy with aspirin and The trial’s primary aim is to ground for such a study, Dr. esomeprazole is safe and well determine whether treatment Jankowski said at the sympo- 15.4% tolerated for preventing the pro- with aspirin and the proton sium, also sponsored by the gression of Barrett’s esophagus pump inhibitor esomeprazole AGA Institute, the American So- of flat and depressed lesions were missed these lesions putting patients to adenocarcinoma. (Nexium, AstraZeneca) can stop ciety for Therapeutic Radiology Since the start of the ran- Barrett’s metaplasia from pro- domized Aspirin Esomeprazole gressing to adenocarcinoma. See Early Data • page 9 Chemoprevention Trial (As- GI & HEPATOLOGY NEWS pECT) in September 2005, 1,192 Presorted Standard 5.8% 6.0% 60 Columbia Rd., Bldg. B U.S. Postage (83%) of the 1,436 patients have PAID markedly different from those used at risk for interval colon cancers. Morristown, NJ 07960 Permit No. 384 Lebanon Jct. KY remained on their medication, CHANGE SERVICE REQUESTED

N EWS and just 33 adverse events have been reported, said lead investi- Screening Symptomatic Surveillance gator Dr. Janusz Jankowski, pro- patients patients patients M EDICAL fessor of medicine, Oxford Uni- by Western physicians. We now know The GIHN piece, referencing Soetik- (n = 616) (n = 549) (n = 654) versity (England), at a meeting G LOBAL Note: Based on data for 1,819 adult patients. on gastrointestinal cancers spon- Source: JAMA sored by the American Society LSEVIER that most flat lesions seen by U.S.- no’s article, helped inform us about an E of Clinical Oncology. based endoscopists are sessile serrat- important (and confusing) problem in ed adenomas (SSAs). SSAs at that time our colon cancer prevention efforts. also were a new and controversial As numerous authors subsequently classification. highlighted (see Gastroenterolo- John I. Allen, MD, MBA, AGAF, is pro- SSAs were first described by Tor- gy. 2016;151:870-8) most cancers, fessor of medicine in the division of lakovic and Snover in 1996 (Gastro- missed at initial colonoscopy, are gastroenterology and hepatology at the enterology. 1996;110:748-55). Dale proximal and frequently develop from University of Michigan, Ann Arbor, and Snover, MD, was my golfing partner SSAs. We continue to work to reduce the Editor in Chief of GI & Hepatology and read pathology slides for our missed cancers and thanks to this News. practice in Minneapolis, so we were seminal article, we have better in- the first gastroenterologists in the sights about how to achieve this goal. Prominent clinical guideline falls short of COI standards

BY JENNIE SMITH 17, Akilah A. Jefferson, MD, and The IOM standards for conflicts cial conflicts of interest, according Frontline Medical News Steven D. Pearson, MD, both of the of interest in guidelines, introduced to the IOM. National Institutes of Health in in 2011, require that less than half For the HCV guidelines, 72% of recent clinical practice guide- Bethesda, Md., re-examined con- the members of any guideline writ- the committee members reported A line for treatment of chronic flict of interest disclosures for the ing committee have a commercial commercial conflicts, along with hepatitis C did not meet the Insti- American Association for the Study conflict, which can include consul- four out of six committee cochairs. tute of Medicine’s standards for of Liver Diseases and Infectious tancies, board memberships, and An analysis of concurrent publica- limiting commercial conflicts of Diseases Society of America’s joint stock in manufacturers of devices tions revealed incomplete disclo- interest, according to results of a 2014 guideline related to novel or treatments. Guideline writing sure of conflicts among authors of new analysis. drug treatments for chronic hepati- committee chairs and cochairs the guideline (JAMA Intern Med. In research published online Jan. tis C virus (HCV) infection. should have no commer- Continued on following page CLINICAL CHALLENGES AND IMAGES bulky appearance, the lesion allowed easy passage What’s your diagnosis? of the endoscope into the stomach. Endoscopic biopsy specimens suggested a malignant tumor of the By Kensuke Adachi, MD, PhD, and Kazuaki Enat- esophagus. su, MD. Published previously in Gastroenterology There were no suspicious lymph nodes or distant (2013;144[1]:32, 251). metastases on preoperative computed tomography. The patient underwent an esophagectomy and previously healthy, 56-year-old man visited our standard three-field lymphadenectomy with gastric A hospital with a 2-month history of dysphagia. replacement via the posterior mediastinal route The patient’s past medical history was unremark- and intrathoracic anastomosis. able. He denied a recent history of weight loss, re- He had an uneventful recovery and was dis- flux symptoms, or food impaction. Laboratory and charged on postoperative day 11. The operative physical test results revealed no abnormalities. specimen is shown in Figure C. According to the Barium swallow esophagogram showed dilatation TMN classification, the postoperative diagnosis was of the esophagus with a filling defect, approximately T2N0M0, equivalent to stage IIA. Fortunately, the 7 cm long, in the intrathoracic esophagus (Figure patient was alive and free of recurrence after 7 years A). Endoscopy also revealed an elastic and large of follow-up. tute polypoid tumor occupying the almost whole lumen

in the mid-esophagus (Figure B). Despite such a The diagnosis appears on page 26. I nst AGA GIHEPNEWS.COM • FEBRUARY 2017 NEWS 7

Continued from previous page were published,” the investiga- The study was funded by an NIH tors wrote. They recommended grant. Dr. Pearson reported receiv- 2017 Jan 17. doi: 10.1001/jamain- “broader and more explicit adop- ing research funding from founda- ternmed.2016.8439). tion” of the IOM’s framework for tions and membership dues paid “Management of levels of com- conflict of interest. by insurance and pharmaceutical Quick quiz mercial [conflict of interest] The study notes that the HCV companies. No other disclosures among guideline committees guideline met all nine of the addi- were reported. remains an important problem tional IOM guideline development Q1. A 40-year-old man presents 5 years after the IOM standards and evidence standards. [email protected] with melena and a significant drop in hemoglobin. He is hy- potensive and tachycardic. He is resuscitated with intravenous fluids and undergoes urgent endoscopy. A 2-cm gastric ulcer is seen in the antrum with a large adherent clot that resists vigor- ous washing for 2 minutes.

In addition to an IV proton pump inhibitor, what is the most appropriate method for treating this ulcer? A. No further therapy is indicated B. Epinephrine injection, shav- ing down the clot with a cold snare, and coaptive coagulation of the underlying vessel C. Combination therapy with epinephrine injection and hemoclip placement over the clot D. Epinephrine injection around the base of the ulcer

Q2. A 34-year-old woman presents with a 3-year history of watery, nonbloody diarrhea with associated weight loss, and recurrent bacterial bronchitis and pneumonias. Laboratory studies show iron deficiency anemia, low 25-OH vitamin D, and a slightly elevated INR. Celiac serologies were negative, and small bowel biopsies revealed near total villous atrophy, increased intraepithelial lymphocytes, and crypt hyperplasia with absent plasma cells.

What is the most appropriate initial treatment strategy? A. Gamma globulin B. Prednisone C. Infliximab D. Gluten-free diet E. Rifaximin

The answers are on page 25.

CORRECTION

In the January 2017 Flashback feature on page 6, in the last para- graph the last sentence should have read “in the 2007 June issue of GI & Hepatology News ...” 8 NEWS FEBRUARY 2017 • GI & HEPATOLOGY NEWS FROM THE AGA JOURNALS Protein-rich diet helps manage type 2 diabetes, NAFLD

BY DEEPAK CHITNIS between June 2013 and March 2015. of these components,” the authors be in the long term, according to Frontline Medical News Subjects were randomized into one stated in the study. “The origin of the authors. Further studies will be protein – animal or plant needed to “show the durability of atients with type 2 diabetes – did not play a major role. the responses and eventual adverse should be put on diets rich in Both high-protein diets un- effects of the diets.” Peither animal or plant protein to expectedly induced strong The study was funded by grants reduce not only liver fat, but insulin reductions of FGF21, which from German Federal Ministry of resistance and hepatic necroinflam- of two cohorts, each of which were was associated with metabolic im- Food and Agriculture and German mation as well, according to a study assigned a diet rich in either animal provements and the decrease of in- Center for Diabetes Research. Dr. published in the February issue of protein (AP) or plant protein (PP) trahepatic lipids [IHL].” Markova and her coauthors did not Gastroenterology (doi: 10.1053/j.gas- for a period of 6 weeks. Median body However, the 6-week time span report any financial disclosures. tro.2016.10.007). mass index in the AP cohort was 31.0 used here is not sufficient to deter- “High-protein diets have shown ± 0.8 kg/m2, and was 29.4 ± 1.0 kg/ mine just how viable this diet may [email protected] variable and sometimes even favor- m2 in the PP cohort. able effects on glucose metabolism The AP diet consisted mainly of and insulin sensitivity in people with meat and dairy products, while le- uman studies to assess the meat and dairy, but their fatty acid type 2 diabetes,” wrote the authors gumes constituted the bulk of the PP Heffects of isocaloric macronu- compositions are quite different. of the study, led by Mariya Markova, diet. The diets were isocaloric and trient substitution are fraught with Dairy has odd-chain fatty acids, MD, of the German Institute of Hu- had the same macronutrient make- difficulty. If one macronutrient is which are protective against type 2 man Nutrition Potsdam-Rehbrücke in up: 30% protein, 40% carbohydrate, increased, what happens to the diabetes, while Nuthetal, Germany. and 30% fat. Seven subjects dropped others? If you observe an effect, is it meat has even- Obesity and insulin resistance have out prior to completion of the study; the phenomenon you were seeking, chain fatty long been linked to liver fat, with of the 37 that remained all the way or an epiphenomenon caused by acids, which excessive amounts causing nonalco- through – 19 in the AP cohort, 18 in changes in the others? may be more holic fatty liver disease (NAFLD). The the PP cohort – the age range was Markova et al. attempted to predisposing “hypercaloric Western style diet,” as 49-78 years. Subjects maintained study a 6-week “isocaloric” in- to disease. Did the authors call it, exacerbates the ac- the same physical exercise regimens crease of animal vs. plant protein the change cumulation of fat deposits in the liver throughout the study that they had (from 17% to 30% of calories as in fatty acids and complicates the health of many, beforehand, and were asked not to protein). However, a decrease of play a role,

regardless of weight. alter them. Hemoglobin A1c levels percent fat from 41% to 30%, and DR. LUSTIG rather than “Remarkably, diets restricted in ranged from 5.8% to 8.8% at base- a reduction in carbohydrate from the change in methionine were shown to prevent line, and evaluations were carried out 42% to 40% occurred commen- amino acids? Lastly, the type of the development of insulin resistance fasting for each subject. surately. This brings up three con- carbohydrate was not controlled and of the metabolic syndrome in Patients in both cohorts had sig- cerns. First, despite the diets being for. Fructose is significantly more animal models [so] the type of pro- nificant decreases in intrahepatic fat “isocaloric,” weight and body mass lipogenic than glucose. Yet they tein may elicit different metabolic content by the end of the trial peri- index decreased by 2 kg and 0.8 were lumped together as “carbo- responses depending on the amino od. Those in the AP cohort saw de- kg/m2, respectively. Reductions in hydrate,” and were uncontrolled. acid composition,” Dr. Markova and creases of 48.0% (P = .0002), while intrahepatic, visceral, and subcuta- So what macronutrient really her coinvestigators noted. “It is there- those in the PP cohort saw a de- neous fat, and an increase in lean caused the reduction in liver fat? fore hypothesized that high-plant- crease of 35.7% (P = .001). Perhaps body mass were noted. So was the These methodologic issues detract protein diets exert favorable effects most importantly, the reductions in diet isocaloric? Protein reduces from the author’s message, and on hepatic fat content and metabolic both cohorts were not correlated to plasma ghrelin levels and is more this study must be considered pre- responses as compared to high in- body weight. In addition, levels of satiating. Furthermore, metabo- liminary. take of animal protein rich in BCAA fibroblast growth factor 21 (FGF21), lism of protein to ATP is inefficient [branched-chain amino acids] and which has been shown to be a pre- compared to that of carbohydrate Robert H. Lustig, MD, MSL, is in the methionine.” dictive marker of NAFLD, decreased or fat. The authors say only that division of pediatric endocrinology, Dr. Markova and her team devised by nearly 50% for both AP and PP calories were “unrestricted.” These UCSF Benioff Children’s Hospital, a prospective, randomized, open-la- cohorts (P less than .0002 for both). issues do not engender “isocaloric” San Francisco; member, UCSF In- bel clinical trial involving 44 patients “Despite the elevated intake and confidence. Second, animal pro- stitute for Health Policy Studies. with type 2 diabetes and NAFLD re- postprandial uptake of methionine tein (high branched-chain amino Dr. Lustig declared no conflicts of cruited at the German Institute of Hu- and BCAA in the AP group, there acid and methionine) consists of interest. man Nutrition Potsdam-Rehbrücke was no indication of negative effects

Endoscopy during pregnancy risks preterm birth teaser

BY DEEPAK CHITNIS “Research in pregnancy outcome in women studies examined pregnancy outcome in upper Frontline Medical News undergoing endoscopy endoscopy (n = 143), two during pregnancy is examined pregnancy out- omen who undergo an endoscopy during scarce,” wrote the authors, come in sigmoidoscopy or Wpregnancy are increasing the chances that led by Jonas F. Ludvigsson, colonoscopy (n = 116), and their baby will be born preterm, or be small for MD, of the Karolinska four examined pregnancy gestational age (SGA), according to research Institutet in Stockholm, adding that there are nine outcome in endoscopic retrograde cholangiopan- published in the February issue of Gastroenter- studies with original data on a total of 379 preg- creatography (n = 120). ology (doi: 10.1053/j.gastro.2016.10.016). nant women undergoing endoscopy; two of these Continued on following page GIHEPNEWS.COM • FEBRUARY 2017 NEWS 9 FROM THE AGA JOURNALS Vedolizumab effective for UC in range of patients in patients with moderate and se- period of up to 46 weeks. The total vedolizumab continued to have far BY DEEPAK CHITNIS vere UC via a multicenter, phase III, length of the study was, therefore, higher rates of clinical response than Frontline Medical News randomized, placebo-controlled tri- 52 weeks; for patients that were did those on placebo, with 46.9% al. This study produced data on 374 re-randomized, follow-up evalua- and 19.0%, respectively (AD, 28.0%; hen treating patients for subjects who had been randomized tions took place every 4 weeks. 95% CI, 14.9-41.1). For those with ulcerative colitis (UC), cli- into cohorts receiving either vedol- A total of 464 patients who were previous TNF antagonist exposure, Wnicians should consider us- izumab intravenously or a placebo. enrolled and completed the study the disparity between vedolizumab ing vedolizumab, because the drug However, this number was deemed were naive to TNF antagonists, and placebo was similarly profound: has been found to be both safe and too low, so a further 521 patients while 367 had previously been 36.1% versus 5.3%, respectively highly effective in patients who have were enrolled for an open-label treated with TNF antagonists un- (AD, 29.5%; 95% CI, 12.8-46.1). never received tumor necrosis factor study and randomized in the same Adverse event rates between na- (TNF)–antagonist treatment and in 3:2 ratio as the previous study. The ive and previously exposed patients those who have but did not benefit former study was called Cohort 1 At week 52, TNF antagonist– were not significantly different, from it, according to a study pub- and the latter called Cohort 2. according to the findings. In naive lished in the February issue of Clini- “Eligible patients had UC for [at naive subjects on vedolizumab patients, 74% of those on vedol- cal Gastroenterology and Hepatology least] 6 months before enrollment, continued to have far higher izumab experienced an adverse (doi: 10.1016/j.cgh.2016.08.044). MCS [Mayo Clinic scores for disease event, and 9% experienced a serious “Approximately 50% of patients activity] from 6 to 12, and endoscop- rates of clinical response adverse event. For those on place- with UC do not respond to induction ic subscores of [at least] 2 within 7 than did those on placebo. bo, those rates were 75% and 16%, therapy with TNF antagonists or lose days before the first dose of study respectively. For patients who had response over time such that, after 1 drug, and evidence of disease ex- previously been on a TNF antago- year of treatment, clinical remission tending [at least] 15 cm proximal to nist, subjects on vedolizumab had is observed in only 17%-34% of pa- the rectum,” the authors explained. successfully. At 6-week follow-up, an 88% rate of adverse events and a tients,” explained the authors of the Vedolizumab was administered at 53.1% of naive subjects receiving 17% rate of serious adverse events, report, led by Brian G. Feagan, MD, baseline, with follow-up evaluations vedolizumab had achieved clini- compared with 84% and 11%, re- of the University of Western Ontario at 2, 4, and 6 weeks. Subjects who cal response, vs. 26.3% of naive spectively, for those on placebo. in London. “Furthermore, the risk of experienced a clinical response subjects on placebo (absolute dif- The study was funded by Millen- serious infection (with immunosup- – defined as an MCS reduction of ference, 26.4%; 95% confidence nium Pharmaceuticals. Dr. Feagan pressants in general, and TNF antag- at least 3 points and 30%, along interval, 12.4-40.4). Similarly, those disclosed serving as a consultant onists specifically) is an important with at least a 1-point reduction with previous TNF antagonist expo- and receiving financial support for concern [so] alternative approaches in rectal bleeding and an absolute sure who were given vedolizumab research from Millennium and other to treatment are needed.” rectal bleeding subscore of either had a 39.0% clinical response rate, companies. No other coauthors re- For this study, Dr. Feagan and his 0 or 1 – were re-randomized into versus 20.6% of those on placebo ported relevant financial disclosures. colleagues turned to the GEMINI 1 cohorts that received the drug ev- (AD, 18.1%; 95% CI, 2.8-33.5). trial, which evaluated vedolizumab ery 4 weeks or every 8 weeks, for a At week 52, naive subjects on [email protected]

Continued from previous page “Stillbirth is recorded from 22 completed gesta- “Earlier recommendations suggest that endos- tional weeks since mid-2008, and before that from copy should only be performed during pregnancy Additionally, the authors noted that, to their gestational week 28. Gestational age was deter- if there are strong indications, and if so, not during knowledge, there are no studies that offer data on mined using ultrasound, and when ultrasound data the second trimester, [but] our study shows that the relative risk of endoscopy during pregnancy, were missing, the first day of the last menstrual endoscopy is unlikely to have a more than margin- and none that followed up subjects after birth. Of period was used for pregnancy start,” the authors al influence on pregnancy outcome independently the few studies that do exist, a handful conclude wrote. of trimester,” the authors concluded. “Neither does that endoscopy during pregnancy is actually safe, The results showed that mothers who had any it seem that sigmoidoscopy is preferable to a full but do not include data on stillbirths and neonatal kind of endoscopy during pregnancy were more colonoscopy in the pregnant woman.” deaths that did not occur immediately after pa- likely to experience a preterm birth or give birth Regarding the latter conclusion, the authors tients underwent endoscopy, which could compro- to a baby who was SGA, with the ARR being 1.54 clarified that “it is possible that in women with mise that data. (95% confidence interval, 1.36-1.75) and 1.30 particularly severe gastrointestinal disease where To address the lack of reliable research on the (95% CI, 1.07-1.57), respectively. However, the endoscopy is inevitable, the physician will prefer a effect of endoscopy on pregnancy, Dr. Ludvigsson risk of other adverse effects, such as stillbirth sigmoidoscopy rather than a full colonoscopy, and and his coinvestigators launched a nationwide or congenital malformation, was not significant: under such circumstances the sigmoidoscopy will study of pregnancies in Sweden that occurred be- Stillbirth ARR was 1.45 (95% CI, 0.87-2.40) and signal a more severe disease.” tween 1992 and 2011, all of which were registered congenital malformation ARR was 1.00 (95% CI, The investigators also noted that their study in the Swedish Medical Birth Registry and the 0.83-1.20). had several limitations, including not knowing the Swedish Patient Registry. The databases revealed Women who were exposed to endoscopy during length of time each endoscopy took, the sedatives 2,025 upper endoscopies, 1,109 lower endosco- pregnancy were more likely to have a preterm and bowel preparations used, the patient’s posi- pies, and 58 endoscopic retrograde cholangiopan- birth, compared with women who had endos- tion during the procedure, and the indication that creatographies, for a total of 3,052 pregnancies copy 1 year before or after pregnancy, but were prompted the endoscopy in the first place. exposed to endoscopy over that time period. not more highly predisposed to SGA, stillbirth, The study was funded by grants from the The primary endpoint of the study was the or congenital malformations. Additionally, when Swedish Society of Medicine and the Stockholm frequency of preterm birth and stillbirth in this data on multiple pregnancies carried by the same County Council, and the Swedish Research Coun- population. To measure this, the investigators used mother were compared, no correlation was found cil. Dr. Ludvigsson and his coauthors did not re- adjusted relative risk (ARR), calculated via Poisson between endoscopy and gestational age or birth port any relevant financial disclosures. regression by using data on 1,589,173 pregnancies weight, if the mother was exposed to endoscopy that were not exposed to endoscopy as reference. during only one of the pregnancies. [email protected] 10 NEWS FEBRUARY 2017 • GI & HEPATOLOGY NEWS FROM THE AGA JOURNALS Propofol safety similar to that of traditional sedatives

BY DEEPAK CHITNIS inclusion in the study. Of those, 27 were deemed monary adverse event rate when compared with Frontline Medical News eligible and were ultimately included. traditional sedative agents,” the authors concluded. “The primary outcomes measured were car- In terms of the risk of developing any of the or doctors performing gastrointestinal en- diopulmonary complications such as hypoxia, if aforementioned complications, of the 20 relevant doscopic procedures, use of propofol as a oxygen saturation decreased to less than 90%; studies, 9 found propofol to be safer versus 6 Fsedative instead of the combination of opioid hypotension, if systolic blood pressure decreased that found traditional sedatives to be the bet- and benzodiazepine carries about the same risk to less than 90 mm Hg; arrhythmias, including bra- ter option, yielding an overall OR of 0.77 (95% of causing cardiopulmonary adverse events, ac- dycardia, supraventricular and ventricular arrhyth- CI, 0.56-1.07) for propofol. For the subanalysis cording to a study published in the February issue mias, and ectopy,” Dr. Wadhwa and his coauthors regarding which type of clinician administered of Clinical Gastroenterology and Hepatology (doi: wrote. “A subgroup analysis also was performed to each sedative, 25 studies contained relevant data, 10.1016/j.cgh.2016.07.013). assess studies in which sedation was directed by of which 9 studies reported gastroenterologists “Because of its popularity, propofol is being used gastroenterologists and was compared with non- administering sedatives, 5 studies reported en- for both simple endoscopic procedures such as gastroenterologists.” doscopy nurses administering sedatives under esophagogastroduodenoscopy and colonoscopy, the supervision of the gastroenterologist, and 11 and advanced endoscopic procedures, [but] de- studies reported either an anesthesiologist, inten- spite the widespread use of propofol, significant ‘Our results showed that propofol sive care unit physician, or critical care physician concerns remain regarding its safety profile,” ac- sedation for gastrointestinal endoscopic administering sedatives. cording to the authors of the study, led by Vaibhav “Gastroenterologist-directed sedation with Wadhwa, MD, of Fairview Hospital in Cleveland. procedures, whether simple or advanced, propofol was noninferior to nongastroenterol- While still used today, the opioid/benzodiaz- did not increase the cardiopulmonary ogist sedation,” Dr. Wadhwa and his coinvesti- epine combination has seen a dramatic decline gators wrote. “The risk of complications was in usage because of its longer recovery time and adverse event rate when compared similar to [that of traditional sedatives] both lower rates of satisfaction among both patients with traditional sedative agents.’ during simple and advanced endoscopic proce- and doctors, according to the authors. Combina- dures.” tions including midazolam, meperidine, pethidine, While the authors point to the sheer size of the remifentanil, and fentanyl. Pooled odds ratios were used to measure and study population as a strength of these results, To compare the safety of propofol with the more compare results. The 27 included studies featured they also note that because this is a study-level traditional sedative combination, Dr. Wadhwa and data on a total of 2,518 patients. Traditional seda- analysis rather than one conducted on an indi- his coauthors conducted a meta-analysis of pub- tives were used on 1,194 of these subjects, while vidual level, there is an inherent limitation to the lished studies in the Medline (Ovid), EMBASE, and the remaining 1,324 received propofol. Regarding study. Furthermore, variations from study to study the Cochrane controlled trials registry databases. hypoxia, 26 of the 27 studies addressed this, of in how propofol was administered to each patient All searches were for research conducted through which 13 concluded that propofol was safer and may have caused heterogeneity in the findings of September of 2014, with the Medline database 9 found that traditional sedatives were safer, with the meta-analysis. A large clinical trial would be search starting in 1960, and the EMBASE and Co- a pooled OR for propofol of 0.82 (95% confidence the next logical step to affirm what this analysis chrane searches starting in 1980, yielding a total of interval, 0.63-1.07). has found. 2,117 studies eligible for inclusion. Twenty-five studies examined hypotension, of However, they wrote, the difference in complica- Of those, 1,568 remained after duplicates were which 9 favored propofol and 10 favored tradition- tions between propofol and other agents might not removed, then 136 were screened after removal al sedatives, for an OR of 0.92 (95% CI, 0.64-1.32). be clinically relevant owing to the lack of any seri- of those deemed irrelevant or otherwise un- Of the 20 studies that included arrhythmia, 8 fa- ous complications such as intubations or deaths in suitable. From those 136, 83 were excluded for vored propofol and 7 favored traditional sedatives, the studies used in this meta-analysis. various reasons – because they featured either for an OR of 1.07 (95% CI, 0.68-1.68). Dr. Wadhwa and his coauthors reported no rele- ineligible populations, or were retrospective stud- “Our results showed that propofol sedation for vant financial disclosures. ies, single-arm studies, or conference abstracts gastrointestinal endoscopic procedures, whether – leaving 53 full-text articles to be evaluated for simple or advanced, did not increase the cardiopul- [email protected]

he use of propofol-mediated sedation and, in compared with the traditional sedation agents, with a combination of a benzodiazepine and Tparticular, anesthetist-directed sedation has the pooled odds ratio of propofol-mediated seda- an opioid. The benefit of the agent may be its become a hot-button item in the landscape of tion was not associated with a safety benefit in pharmacodynamics, which allow for a rapid gastrointestinal endoscopy by virtue of terms of the development of hypoxia targeting of the appropriate level of sedation its overall cost. Some experts place the or hypotension. We also found that the and enhanced recovery, which lead to both cost of this at over $1.1 billion annually. safety profile of propofol-mediated se- augmented throughput and patient satisfaction. Recent studies stemming from a large dation was equivalent whether it was This has been well studied for endoscopist-di- administrative database question the administered by a gastroenterologist or rected propofol sedation when compared to safety of propofol-mediated sedation nongastroenterologist. traditional sedation regimens and may be true when compared to the standard com- Does this answer the question? I for anesthesiologist-directed sedation, although bination of a benzodiazepine and opi- think it is safe to say that for healthy I know of no comparative data. Propofol seda- oid. Still other studies have found that patients undergoing elective upper tion is a much more expensive alternative for anesthesiologist-directed sedation did endoscopy and colonoscopy, there healthy patients undergoing elective ambulato- not improve the rate of polyp detection DR. VARGO is no safety benefit of propofol-me- ry endoscopy. or polypectomy. Given these findings, diated sedation, compared with our research group decided to embark upon a traditional agents. Our data also suggest that John Vargo, MD, MPH, AGAF, is the department meta-analysis to further study the safety profile of with appropriate patient selection and train- chair of gastroenterology and hepatology at Cleve- propofol when compared to the combination of a ing, endoscopist-directed propofol sedation is land Clinic and vice chairman of Cleveland Clinic’s benzodiazepine and opioid. We found that when a viable alternative to the traditional sedation Digestive Disease Institute. He declared no conflicts.

18 NEWS FROM THE AGA FEBRUARY 2017 • GI & HEPATOLOGY NEWS Join AGA in supporting GI research ecades of research have rev- brought on by digestive diseases. expressed in and ultimately for patients.” olutionized the care of many The AGA Research Foundation’s digestive-type By joining others in donating to the Ddigestive disease patients. mission is to raise funds to support epithelia, allow- AGA Research Foundation, you can These patients, as well as every- young researchers in gastroenterol- ing me to better help fill the funding gap and protect one in the GI field, clinicians and ogy and hepatology. The foundation understand the next generation of investigators. researchers alike, have benefited provides a key source of funding at the molecular Help provide critical funding to from the discoveries of dedicated a critical juncture in a young inves- basis of GI dis- young researchers today by making investigators, past and present. As tigator’s career. eases. My goal a donation to the AGA Research the charitable arm of the American Rani Richardson, 2016 AGA In- is to create a Foundation on the foundation’s Gastroenterological Association vesting in the Future Student Re- MS. RICHARDSON career in med- website at www.gastro.org/con- (AGA), the AGA Research Founda- search Fellowship Award Recipient ical research tribute or by mail to 4930 Del Ray tion contributes to this tradition of said, “Using this award, I plan to and develop more ways to make Avenue, Bethesda, MD 20814. discovery to combat the continued study the cytoskeletal interme- biomedical research meaningful for lower quality of life and suffering diate filament proteins that are clinical health care professionals, [email protected] Annual AGA Tech Summit Register for DDW® before returns to Boston in 2017 the early-bird deadline

GA is excited to return to Bos- http://techsummit.gastro.org. egistration for AGA members trointestinal surgery, and related Aton for its eighth annual Tech Ropened Jan. 11, and general reg- fields. Whether you work in pa- Summit on April 12-14, 2017, at Have a novel idea or innovation? Ap- istration opened on Jan. 18. Register tient care, research, education, or the InterContinental Hotel. We’ve ply for the AGA “Shark Tank” by March 22 to save at least $80; administration, the DDW program assembled prominent individuals in Calling all companies and entrepre- registration is complimentary up offers something for you. For more the physician, medtech, and regula- neurs with an innovative technology until this date for member trainees, information regarding why you tory communities to lead attendees or Food and Drug Administration– students, and postdoctoral fellows. should attend DDW, what’s includ- through a program that’s both in- regulated product. If you are looked in registration, and more, visit formative and inspirational. ing to get it financed, licensed, or Why attend DDW? ddw.org. This is an ideal opportunity to distributed, you are encouraged to Digestive Disease Week is the Registration is also now open for explore critical elements impacting submit an application for an oppor- world’s leading educational fo- the AGA Postgraduate course on how GI technology evolves from tunity to present during the “Shark rum for academicians, clinicians, May 6 and 7 at DDW 2017. Visit concept to reality, including what it Tank” session at the 2017 AGA Tech researchers, students, and train- pgcourse.gastro.org to register. takes to obtain adoption, coverage, Summit. A panel of business devel- ees working in gastroenterology, and reimbursement in a continually opment leaders, investors, entrepre- hepatology, GI endoscopy, gas- [email protected] evolving health care environment. neurs, and other strategic partners We hope to see you this spring will provide valuable feedback. in Boston for a truly unique experience. Learn more and register at [email protected] AGA comment on ABIM announcement Access our MACRA or more than a year, AGA has ABIM deemed AGA’s approach to be Fpushed the American Board inconsistent with its own philoso- resource collection of Internal Medicine (ABIM) to phy. Nonetheless, we are still in the eliminate high-stakes testing and midst of an evolution. AGA will con- repare for 2017 with AGA’s experts presented a series of webi- reform the maintenance of cer- tinue to work with our sister GI and PMedicare Access and CHIP Re- nars on relevant MACRA protocols tification (MOC) system into one internal medicine societies to bring authorization Act of 2015 (MACRA) to help clinicians prepare for Medi- that’s personalized and reflective about change that supports mean- resources, which are available in care changes starting this year. of the realities of practice. ingful lifelong learning through the the AGA Community resource li- Each webinar preceded an Ask ABIM’s listening tour is over. In least intrusive means possible. brary. This includes webinars, a tip the Expert session in the AGA Com- December 2016, they announced In the meantime, if your pro- sheet, and discussion threads. munity forum. Members brought the addition of an option for a fessional situation requires you The webinars and discussions their wide range of questions to the 2-year “knowledge check-in.” Al- to maintain certification, please in the community are available to forum, including discussions about though ABIM can point to nominal visit ABIM’s blog for more infor- members only, and contain infor- MACRA basics, as well as meticulous progress by making the assessment mation. AGA tools such as the mation on the following topics: situation-based recording scenarios. available outside its testing centers, Digestive Diseases Self-Education • Intro to MACRA. This members-only library can they have not addressed cost, per- Program® can help you prepare. • 2016 PQRS Quality Reporting be accessed at community.gastro. sonalization, or the impact on pa- Visit http://www.gastro. through the AGA Digestive Health org/MACRA. For more information, tient care of such assessments. org/career-center/mainte- Recognition Program. including a timeline, downloadable Despite AGA’s diligent efforts nance-of-certification for the • Preparing for MIPS. guides, and the latest MACRA news, to co-create a new MOC process latest updates and information The materials were collected visit gastro.org/MACRA. – which included creating G-APP, on MOC. from a series of webinars and constant communication, and par- eQ&As in December, when topic [email protected] ticipation in numerous summits – [email protected] UCERIS is a trademark of Salix Pharmaceuticals or its affiliates. Di Stefano AF, et al. Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide All rights reserved. UCE.0092.USA.16 September 2016 Printed in USA. formulation. Br J Clin Pharmacol. 2005;61(1):31-38. 20 IBD AND INTESTINAL DISORDERS FEBRUARY 2017 • GI & HEPATOLOGY NEWS

tients are more likely to have colonic develop CDI starting at younger ages, Use vancomycin or FMT dysbiosis. more often acquire it from communi- AGA CPU from page 1 CDI can present atypically in IBD. ty settings, and may lack the typical Underlying colitis leads to colonic colonoscopic features of CDI. Simple and the emergence of highly virulent and surgery. Rates of CDI have risen dysbiosis and loss of resistance to colonization with C. difficile without C. difficile strains. Patients with CDI among both the ulcerative colitis bacterial colonization, which permits infection also is more common in pa- and underlying IBD are at particular and Crohn’s disease populations, but CDI to develop even when patients tients with IBD than in those without risk of hospitalization, intensifica- are higher in the setting of ulcerative have not recently received antibiot- IBD, the experts note. tion of medical therapies for IBD, colitis, perhaps because these pa- ics. Patients with IBD also tend to The authors contradict guidelines from both the American College of Gastroenterology and Infectious Diseases Society of America by recommending consideration of vancomycin over metronidazole for treatment of CDI. Not only are C. difficile treatment failures with metronidazole rising, but vancomycin was more effective than metronidazole in a recent post hoc analysis (Clin Infect Dis. 2014;59[3]:345-54) of two large multicenter phase III trials. Another phase III trial (N Engl J Med. 2011;364:422-31) found vancomycin noninferior to fidaxomicin for CDI. The experts recommend hospitalization for patients with IBD and CDI who present with profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other signs and symptoms of sepsis. Aggressive monitoring and treatment are especially important because it can be difficult to distinguish an IBD flare, which merits immunosuppression, from superim- posed CDI, which might exacerbate the underlying infection. Few studies are available to help guide the decision about when to intensify steroids and other immunosuppressives in IBD patients with acute CDI. Thus, the experts suggest delaying this step until after starting therapy for CDI, but note that the decision should be indi- vidualized pending more robust data. The authors emphasized the potential role of fecal microbiota transplantation (FMT), which has been shown to be very effective in both immunocompetent patients with CDI and those who are immunosup- pressed, which includes those on IBD therapies. They recommend considering referral for FMT as early as the first recurrence of CDI in patients with IBD, particularly because of the strong safety and efficacy profile of FMT, the risk of complications from CDI in IBD patients, and scarce data on antibiotic therapy for recurrent CDI in the setting of IBD. Dr. Khanna disclosed consulting relationships with Rebiotix and Sum- mit Pharmaceuticals. Senior author Ciaran P. Kelly, MD, disclosed serving as a consultant to Merck, Seres Ther- apeutics, Summit Pharmaceuticals, and Takeda Pharmaceuticals. There were no other relevant disclosures.

[email protected] GIHEPNEWS.COM • FEBRUARY 2017 IBD AND INTESTINAL DISORDERS 21 Oral, liquid supplement improves lactose intolerance

BY WHITNEY MCKNIGHT Stool samples were collected from both groups Frontline Medical News at days 0 and 36. After day 36, all participants were asked to resume eating dairy foods. At day dults with self-reported lactose intol- 66, stool samples were once again collected. erance were shown to have significant Changes in the microbiome at all endpoints were Aimprovement in their clinical outcomes, measured by testing the stools via polymerase including abdominal pain, after consuming an chain reaction. oral, liquid supplement intended to increase Of the 30 study arm participants for whom

lactose-fermenting gut bacteria, M. Andrea complete stool samples were available, 27 were ock

Azcarate-Peril, PhD, assistant professor of found to have had a bifidobacterial response at inks T medicine at the University of North Carolina, day 36, including a significant increase in the Chapel Hill, and her colleagues have shown in lactose-fermenting Bifidobacterium, Faecalibac- 119/T H eiko

a small phase IIa study (Proc Nat Acad Sci. doi: terium, and Lactobacillus species. The remaining H 10.1073/pnas.1606722113). three participants in the study arm were consid- In a placebo-controlled, double-blind trial, ran- ered nonresponders. 10.1186/1475-2891-12-160]. domly assigned in a 2:1 ratio and conducted at In an interview, Andrew Ritter, whose compa- “We’re super excited about these results,” said two U.S. sites, highly purified (more than 95%) ny, Ritter Pharmaceuticals, sponsored the trial, Mr. Ritter. “This is really one of the first clinical short-chain galactooligosaccharide (GOS) was reported that of the 36 study arm participants studies in a lactose-intolerant population that given to 42 adults with a self-reported history who had reported abdominal pain pretreatment, shows changes in the microbiome.” As to how long of lactose intolerance, confirmed by a hydrogen 18 said they no longer had the pain at either before the treatment will be ready for the Food and breath test administered after a 25-g lactose endpoint, day 36 or day 66 (P = .019); three Drug Administration approval process, Mr. Ritter challenge. The 20 controls were given a corn of 19 in the placebo group reported they no said, “We’re probably just a couple of years away.” syrup mixture formulated according to the same longer had abdominal pain at either endpoint. Two coauthors are advisers to Ritter Pharma- sweetness and consistency as the test drug. The study group was also six times more likely ceuticals, which provided the highly purified GOS Each study arm was started on its regimen at to report lactose tolerance at day 66 compared used in the study. The North Carolina Agriculture 1.5 g daily, with incremental increases in dose with their pretreatment levels (P = .0389); 28% Foundation also provided funding for the study. every 5 days until reaching 15 g. Beginning with of the placebo arm reported lactose tolerance their first dose at day 1, through day 35, all par- at the endpoints. These results were previous- [email protected] ticipants avoided consumption of dairy foods. ly published in Nutrition Journal in 2013 [doi: On Twitter @whitneymcknight High red meat consumption linked to diverticulitis

BY DEEPAK CHITNIS ated complications, inflammatory which investigators would monitor servings of poultry or fish did not Frontline Medical News bowel disease, or a GI-related can- medical history, disease outcomes, have a higher risk of diverticulitis. cer at baseline were excluded from and so on – occurring every 4 years “We also observed that unpro- en who consume higher quan- this analysis, leaving 46,461 eligible during the follow-up period. Red cessed red meat, but not processed Mtities of red meat are at an subjects. Of those, 764 developed meat consumption was divided in red meat, was the primary driver increased risk of developing diver- diverticulitis. quintiles of 1-5, with 1 being the for the association between total ticulitis, especially if they’re eating lowest amount and 5 red meat and risk of diverticulitis,” unprocessed red meat, according to and being the highest. the authors explained. “Compared a new study published in Gut. The entirety of with processed meat, unprocessed “In our prior analysis from a large the follow-up period meat (e.g., steak) is usually con- prospective cohort study, the Health constituted 651,970 sumed in larger portions, which Professionals Follow-Up Study person-years. Average could lead to a larger undigested (HPFS), we found that red meat in- servings of total red piece in the large bowel and intake, independent of fiber, may be meat per week were duce different changes in colonic os . com associated with a composite outcome T 1.2 in quintile 1, com- microbiota [and] higher cooking o of symptomatic diverticular disease, pared to 5.3 in quintile temperatures used in the prepa- which included 385 incident cases ockp H 3 and 13.5 in quintile ration of unprocessed meat may over 4 years of follow-up,” wrote the 5. Those in the highest influence bacterial composition or authors, led by Andrew T. Chan, MD, quintile had a multivari- proinflammatory mediators in the

AGAF, of Massachusetts General Hos- ©F use / TH inks T able risk ratio of 1.58 colon.” pital, Boston. Dr. Chan added that “in (95% CI, 1.19-2.11; P = Although medical information the present study, we updated this Subjects in the HPFS responded .01), indicating a significantly higher and self-reports were validated, analysis, which allowed us to pro- to questionnaires regarding their risk for developing diverticulitis. In there are inherent possible limita- spectively examine the association dietary habits, with questions spe- terms of unprocessed red meat, the tions to self-reported data, such between consumption of meat (total cifically asking if they consumed average number of servings per week as misremembering the amount of red meat, red unprocessed meat, red red meat and/or unprocessed red were 0.8 for the lower quintile, 3.2 meat consumed or reporting incor- processed meat, poultry, and fish) meat and at what frequency. Nine for quintile 3, and 8.6 for quintile 5, rect amounts. Residual confounding with risk of incident diverticulitis in responses to each question were yielding a risk ratio of 1.51 (95% CI, may have occurred despite adjust- 764 cases over 26 years of follow-up.” possible, with the lowest being “nev- 1.12-2.03, P = .03) when comparing ment of the data to account for it. Dr. Chan and his coinvestigators er or less than once per month” to the highest and lowest cohorts. The The National Institutes of Health conducted a prospective cohort “six or more times per day.” These increase in risk, however, leveled off funded the study. The authors re- study using subjects from the on- questionnaires were sent out every after about 6 servings of red meat ported no conflicts of interest. going HPFS. Men who already had 2 years during the follow-up period, per week, and was found to be non- a diagnosis of diverticulitis, associ- with more extensive follow-ups – at linear (P = .002). Those who ate more [email protected] 24 ENDOSCOPY, PANCREAS & BILIARY TRACT FEBRUARY 2017 • GI & HEPATOLOGY NEWS Mild, moderate hypertriglyceridemia tied to pancreatitis

BY MARY ANN MOON should be considered a risk factor, measurements and were followed This linear association persist- Frontline Medical News while the European Society of Car- for a median of 6.7 years. During ed after the data were adjusted to diology and the European Athero- that time, 434 of these participants account for potential confounders ild to moderate hypertri- sclerosis Society set the cutoff at developed acute pancreatitis. such as patient age, sex, body mass glyceridemia, not just severe 885 mg/dL, said Simon B. Pedersen, The risk of developing acute pan- index, smoking status, alcohol in- Mhypertriglyceridemia, is MD, of the department of clinical creatitis increased with increasing take, and education level, as well as associated with increased risk of biochemistry, Herlev and Gentofte triglyceride levels starting at the the presence or absence of hyper- acute pancreatitis, according to a Hospital, Copenhagen University, mildly elevated level of only 177 mg/ tension, diabetes, alcohol use, gall- report published in JAMA Internal and his associates. dL. Compared with normal triglycer- stone disease, and statin therapy. Medicine. To examine whether lower tri- ide levels of less than 89 mg/dL, the This study was supported by the Severe hypertriglyceridemia is glyceride levels also put patients risk increased with a hazard ratio of Herlev and Gentofte Hospital and a recognized risk factor for acute at risk for acute pancreatitis, the 1.6 at 89-176 mg/dL, an HR of 2.3 at Copenhagen University Hospital. Dr. pancreatitis, but “there is no con- investigators analyzed data from 177-265 mg/dL, an HR of 2.9 at 266- Pedersen reported having no relevant sensus on a clear threshold above two large prospective longitudi- 353 mg/dL, an HR of 3.9 at 354-442 financial disclosures; one of his asso- which triglycerides” raise that risk. nal studies of the general Danish mg/dL, and an HR of 8.7 at 443 mg/ ciates reported ties to AstraZeneca, The American College of Gastroen- population. They included 116,550 dL or above, Dr. Pedersen and his Merck, Omthera, Ionis, and Kowa. terology and The Endocrine Society consecutive men and women who associates said (JAMA Intern Med. state that levels over 1,000 mg/dL provided nonfasting triglyceride 2016;176:1834-42). [email protected] Half of new AMAs do not lead to primary biliary cholangitis

BY LORI LAUBACH Geraldine Dahlqvist, MD, and her PBC. Results showed the prevalence of normal in 13% of patients, while Frontline Medical News associates examined 720 patients of AMA-positive patients with- cirrhosis was found in 6%. Among whose AMA tests were registered out evidence of PBC was 16.1 per the patients with normal ALP and early half of newly detected anti- during a 1-year census period. 100,000 inhabitants. It was four (all no evidence of cirrhosis, the 5-year Nmitochondrial antibodies (AMAs) They were divided into groups AMA-positive patients) to six (PBC incidence rate of PBC was 16%. Find in clinical practice do not lead to a according to whether they were patients) times higher in women the full story in Hepatology (doi: diagnosis of primary biliary cholangi- newly diagnosed (275), were pre- than in men. Normal serum alkaline 10.1002/hep.28559). tis (PBC), according to a prospective viously diagnosed (216), or had a phosphatases (ALP) were 74%, and study. nonestablished diagnosis (229) of were 1.5 times above the upper limit [email protected] GIHEPNEWS.COM • FEBRUARY 2017 ENDOSCOPY, PANCREAS & BILIARY TRACT 25 AGA CliniCAl P r ACtiC e U P dAte Commentary: Scope guidelines are an improvement

BY DOUG BRUNK notes that the two major changes to given differences among manufactur- out the limitations of these modali- Frontline Medical News the 2016 guidelines are language to ers’ instructions and varied instru- ties. They wrote, “the per procedure maintain consistency with the 2015 ment designs.” However, Dr. Hutfless culture surveillance modality sug- hile the 2016 Multi-Soci- Food and Drug and Dr. Kalloo point out that “an in- gested by the FDA is not cost effec- ety Task Force Endoscope Administration dividual or group of individuals may tive unless the unit’s transmission WReprocessing Guidelines endoscope need to be identified to keep up with probability of carbapenem-resistant are an improvement over the 2011 reprocessing the [Food and Drug Administration], Enterobacteriaceae (CRE) is 24% or guidelines, some of the minor chang- communications, [Centers for Disease Control], manu- greater. Sterilization with ethylene es are unlikely to guarantee against and statements facturer, and professional societies in oxide is problematic because a unit prevention of future outbreaks, ac- suggesting great- order to modify and implement the that used this approach still encoun- cording to Susan Hutfless, PhD, and er monitoring changes to the cleaning and training tered an endoscope with CRE detect- Anthony N. Kalloo, MD. and tracking of protocols and update the training of ed by culture. This unit also incurred “The prevention of future out- the endoscope all individuals in the unit.” extra costs to purchase additional breaks is left to the manufacturers throughout the DR. HUTFLESS Recommendation no. 24 is new scopes due to the longer reprocess- to modify their protocols and the clinical units and and includes a suggestion consis- ing time for sterilization” (Gastroin- endoscopy units to adopt the proto- cleaning rooms, including timing of tent with the 2015 FDA endoscope test Endosc. 2016 Aug;84:259-62). cols rapidly,” the authors, both from events and who performs the key reprocessing communications. In 2016, the FDA approved the first Johns Hopkins University, Baltimore, steps. Dr. Hutfless directs the Johns “Beyond the reprocessing steps dis- disposable colonoscope, which is wrote in a commentary about the Hopkins Gastrointestinal Epidemiol- cussed in these recommendations, expected to be available in the United 2016 guidelines, which contain 41 ogy Research Center, while Dr. Kalloo no validated methods for additional States in early 2017. Dr. Hutfless and recommendations and were en- directs the university’s division of duodenoscope reprocessing cur- Dr. Kalloo ended their commentary dorsed by the AGA. “The guidelines gastroenterology and hepatology. rently exist,” the guidelines state. by suggesting that a disposable endo- will make it possible to better track A specific change to the 2016 “However, units should review and scope with an elevator mechanism, the source of future outbreaks if the guidelines includes recommendation consider the feasibility and ap- though not currently available, could tracking and monitoring suggest- no. 5, which has been revised to rec- propriateness for their practice of be a solution to several of the unre- ed is performed.” They added that ommend “strict adherence” to man- employing one or more of the addi- solved issues that were present in the current cleaning paradigm for ufacturer guidance. “The expectation tional modalities suggested by the the 2003, 2011, and 2016 guidelines. duodenoscopes “is ineffective and is that all personnel will remain FDA for duodenoscopes: intermit- “If the outbreaks persist after the these guidelines reflect changes to up to date with the manufacturer tent or per procedure culture sur- use of disposable endoscopes, it is contain, rather than prevent, future guidelines and that there will be doc- veillance of reprocessing outcomes, possible that it is some other product outbreaks.” umentation of the training,” Dr. Hut- sterilization with ethylene oxide gas, or procedure within the endoscopic The commentary, which is sched- fless and Dr. Kalloo wrote. The 2016 repeat application of standard high procedure that is the source of the uled to appear in the February 2017 guidelines specifically state that a level disinfection, or use of a liquid infectious transmission.” issue of Gastroenterology (doi: “single standard work process within chemical germicide.” 10.1053/j.gastro.2016.12.030), one institution may be insufficient, Dr. Hutfless and Dr. Kalloo pointed [email protected] Quick quiz answers

Q1. Answer: B References creased in celiac disease, they are absent in Critique: The rebleeding rate for ulcers with 1. Jensen D.M., Kovacs T.O., Jutabha R., et al. CVID. an adherent clot with medical therapy alone Randomized trial of medical or endoscopic The initial treatment strategy for CVID is 30%-35%. therapy to prevent recurrent ulcer hemor- typically includes oral corticosteroids, either Randomized controlled studies have shown rhage in patients with adherent clots. Gastro- prednisone or budesonide, with other immu- that endoscopic treatment of adherent clots enterology. 2002;123:407-13. nosuppressants such as the thiopurines or (with combination therapy of epinephrine and 2. Kahi C.J., Jensen D.M., Sung J.J., et al. En- anti–tumor necrosis factor agents reserved coagulation) can decrease the rebleeding rate doscopic therapy versus medical therapy for steroid-dependent or refractory disease. to less than 5%. for bleeding peptic ulcer with adherent Gluten-free diet is ineffective for the treat- A meta-analysis has found that endoscopic clot: A meta-analysis. Gastroenterology. ment of CVID-associated enteropathy. In- therapy is superior to medical therapy for 2005;129:855-62. travenous immunoglobulin therapy reduces preventing recurrent bleeding from peptic ul- the frequency of infections associated with cers with an adherent clot, but no differences Q2. Answer: B CVID, but does not affect the noninfectious GI in the need for surgery, duration of hospital- Objective: Recognize the features of common symptoms. ization, number of transfusions, or mortality variable immune deficiency (CVID)–associated While bacterial overgrowth can occur in rate are observed. noninfectious gastrointestinal manifestations. CVID, it is typically the consequence of the Epinephrine therapy alone is never recom- Explanation: This patient has gastrointestinal luminal changes, not the cause. mended as it has been shown to be inferior manifestations of CVID, which can present to combination therapy, or thermal or me- similarly to celiac disease or inflammatory Reference chanical therapy alone. bowel disease. 1. Agarwal S., Mayer L. Gastrointestinal Choice C is not appropriate, as the clot needs Histologically, intestinal biopsies will re- manifestations in primary immune disorders. to be pared down to expose underlying stigma- veal villous atrophy, crypt hyperplasia, and Inflamm Bowel Dis. 2010;16:703-11. ta. Merely placing a clip over a clot is unlikely intraepithelial lymphocytosis similar to celiac to ligate the vessel and lead to hemostasis. disease. However, while plasma cells are in- [email protected] 26 GI ONCOLOGY FEBRUARY 2017 • GI & HEPATOLOGY NEWS Mutations missed in early-onset colorectal cancer

BY BIANCA NOGRADY PERSPECTIVE ally associated with CRC, including Frontline Medical News ATM, ATM/ CHEK2, BRCA1, BRCA2, Multigene testing needed for diagnosis CDKN2A, and PALB2. s many as one in six patients The authors pointed out that the with early-onset colorectal his study illustrates the short- sition to cancer and will expand multigene panel testing approach Acancer (CRC) have a pathogenic Tcomings of current algorithms current knowledge regarding the enables identification of hereditary genetic mutation, but around one- for diagnosing and managing associated phenotypes, further cancer syndromes in patients who third of these patients may not have younger patients with CRC. First, supporting the cost-effectiveness might not have otherwise met the met the criteria for genetic testing for although family history is one of testing that can guide manage- criteria for testing. at least one of their mutations under of the main components used to ment for patients with cancer and “Importantly, 24 of 72 patients current guidelines, researchers say. stratify an individual’s risk for their at-risk relatives. The study (33.3%) with pathogenic mutations Rachel Pearlman, MS, CGC, of The CRC, it is imperfect because only found germline mutations in one did not meet NCCN Guidelines for at Ohio State University Comprehensive one in five younger patients with in six patients with CRC and has least 1 of the gene(s) in which they Cancer Center, and her coauthors re- CRC reported having a first-de- argued for comprehensive germ- were found to have a mutation,” the ported the results of multigene panel gree relative with CRC. Second, line genetic testing of patients di- researchers noted. These included testing of 450 patients aged under although clinical criteria define agnosed at younger than 50 years. three patients with MMR-deficient 50 years, from 51 institutions, who the phenotypes typically associat- tumors who had additional muta- had been diagnosed with CRC (JAMA ed with specific gene mutations, Eduardo Vilar-Sanchez, MD, PhD, tions in genes that would not have Oncol. 2016 Dec 15. doi: 10.1001/ variability in penetrance and is in the department of clinical been assessed, one patient with an jamaoncol.2016.5194). expressivity can result in overlap cancer prevention and clinical MMR-proficient tumor who was Overall, 16% of patients were among the different hereditary cancer genetics program at The also found to have Lynch syndrome, found to have a pathogenic or likely cancer syndromes (e.g., BRCA University of Texas MD Anderson and six patients with BRCA1/2 mu- pathogenic cancer susceptibility germline mutations in younger Cancer Center, Houston. Elena M. tations. gene mutations, with 83.3% having patients with CRC). Stoffel, MD, is in the department “Previous studies have reported at least one gene mutation. The findings of this large pop- of internal medicine at the Uni- early-onset CRC in women with Thirty-seven patients had Lynch ulation-based study demonstrate versity of Michigan, Ann Arbor. BRCA1 mutations and BRCA2 muta- syndrome; 13 were MLH1, 16 were that the incorporation of multi- These comments are adapted tions in families with familial colo- LSH2, 1 patient was MSH2/monoal- gene panel genetic testing in the from an editorial (JAMA Oncology. rectal cancer type X,” they noted. lelic MUTYH, 2 were MSH6, and 5 evaluation of patients with CRC 2016 Dec 15. doi: 10.1001/jama- The Ohio Colorectal Cancer Preven- were PMS2. will increase the diagnosis of oncol.2016.5193). No conflicts of tion Initiative (OCCPI) is supported “While the prevalence of Lynch individuals with genetic predispo- interest were declared. by a grant from Pelotonia, and by the syndrome reported herein (8.4%) National Cancer Institute. Myriad is consistent with previous publi- Genetics donated next-generation cations, this is the first study to our early-onset CRC,” the authors wrote. But for 145 patients, their ge- sequencing testing. Nine authors knowledge to determine the preva- Forty-eight patients (10.7%) had netic variants were of uncertain disclosed ties with private industry, lence and spectrum of other heredi- mismatch repair–deficient tumors, significance. Thirteen patients including Myriad Genetics. tary cancer syndromes (8%) found in nine of which were in high-pene- had mutations in high- or moder- an unselected series of patients with trance genes linked to CRC risk. ate-penetrance genes not tradition- [email protected] CLINICAL CHALLENGES AND IMAGES The diagnosis Carcinosar- coma is a rare Answer to the “What’s your malignant entity, diagnosis?” on page 6: So-called representing carcinosarcoma of the esophagus less than 2% of all esophageal tute he operative specimen micro- neoplasms. It Tscopically harbors moderately usually shows differentiated squamous carcino- a bulky ap- I nst AGA matous (the central nest) as well as pearance of an and give early symptoms. This agnosis, followed by operative re- sarcomatous (the remainder of the intraluminal polypoid lesion ow- allows for earlier detection and section, remains the mainstay for field) components with a transition- ing to predominant sarcomatous treatment; therefore, this tumor this entity to produce significant al zone (Figure D). This composite development with little stromal was previously believed to carry long-term survival. feature is compatible with that of proliferation. The exophytic intra- a favorable prognosis despite carcinosarcoma of the esophagus. murally growing tumors should its size, as in the case reported References Immune staining with vimentin include this disease in the differ- herein. However, current reports 1. Hung J.J., Li A.F., Liu J.S., et al. is strongly and diffusely positive ential diagnosis. Recent studies have shown the converse result Esophageal carcinosarcoma with only in the mesenchymal element have supported the metaplastic that this earlier detection may not basaloid squamous cell carcinoma (Figure E), whereas staining with theory regarding oncogenesis, translate to a better outcome.2 and osteosarcoma. Ann Thorac cytokeratin AE1/AE3 is positive not whereas the collision concept The sarcomatous component may Surg. 2008;85(3):1102-4. only for the epithelial component, has fallen out of favor; therefore, accompany late metastasis target- 2. Madan A.K., Long A.E., Weldon but also for spindle-shaped cells most esophageal carcinosarcomas ing the liver as well as peritoneal C.B., et al. Esophageal carcino- (Figure F), suggesting evidence for are classified into so-called car- and pleural surfaces. Treatment of sarcoma. J Gastrointest Surg. gradual dedifferentiation of squa- cinosarcoma.1 It has such short this disease does not differ from 2001;5(4):414-7. mous carcinomatous cells into sar- doubling time that it can clini- that of other malignancies in the comatous cells. cally contribute to rapid growth esophagus. Early detection and di- [email protected] GIHEPNEWS.COM • FEBRUARY 2017 GI ONCOLOGY 27 Gastric cancer yields to growth hormone antagonist

BY NEIL OSTERWEIL expression in gastric cancer sam- robust expression of GHRH-R, size (P = .031) and high pathologic Frontline Medical News ples from 106 patients, using compared with normal tissues.” tumor stage (P = .001). Increasing immunohistochemistry staining In 50 samples, GHRH-R was de- expression of GHRH-R was also t sounds counterintuitive, but of primary tumors and adjacent termined to be overexpressed, and significantly associated with worse targeting a neuropeptide hor- normal tissues. They found that this overexpression was significantly overall survival (P less than .001). Imone produced in the hypothal- gastric cancer tissues “exhibited associated with both greater tumor Continued on following page amus may be an effective strategy for treating gastric cancer, the second most common cause of cancer deaths worldwide, investigators from China and the United States contend. Growth hormone–releasing hormone (GHRH) and its receptor (GHRH-R) are found primarily in the anterior pituitary gland, but are also present in gastric cancers, other solid tumors, and lymphomas. Increased levels of GHRH-R in tumor samples from patients with gastric cancer are associated with poor outcomes, noted An- drew V. Schally, PhD, MD, DSc, of the University of Miami, and his colleagues at the Shantou (China) University Medical College.

Growth hormone–releasing hormone and its receptor are found primarily in the anterior pituitary gland, but are also present in gastric cancers, other solid tumors, and lymphomas.

Furthermore, an experimental peptide drug labeled MIA-602 that targets GHRH-R inhibited the growth of gastric cancer cell lines and human tumor xenografts in mice, the investigators reported in the journal PNAS. “The GHRH receptor is both a biomarker that can confirm prognosis and a therapeutic target,” Dr. Schally said in a statement.

Elevated GHRH-R expression in tumors GHRH-R antagonists such as MIA- 602 work through downregula- tion of the p21-activated kinase 1 (PAK1)–mediated signal transduc- er and activator of transcription 3 (STAT3)/nuclear factor–kappaB (NF-kappaB) inflammatory pathway. This pathway is involved in the interplay between inflammatory processes and intracellular signaling thought to be the cause of gastric cancer tumorigenesis and progression, the investigators explained. They first looked for GHRH-R 28 GI ONCOLOGY FEBRUARY 2017 • GI & HEPATOLOGY NEWS

Continued from previous page In addition, the experimental The cancer suppression effects of MAI-602 work through inhibition agent “exhibited remarkable in- They confirmed these findings hibitory effects on tumor growth in samples from a multinational of STAT3/NF-kappaB inflammatory signaling. In vitro and in vivo, in vivo” in mice with human tu- cohort of patients, which again MAI-602 decreased the expression of both GHRH and GHRH-R. mor xenografts (P less than .001). showed that the highest levels of Finally, they showed that the GHRH-R expression were associ- cancer suppression effects of MAI- ated with poor overall survival (P significantly higher in tumor tis- cer cells, the investigators tried it 602 work through inhibition of less than .001). The authors also sues than normal control tissues at various doses in three human STAT3/NF-kappaB inflammatory looked at messenger RNA expres- (P less than .001). gastric cancer cell lines, and found signaling. In vitro and in vivo, sion and gene copy number in 65 that it inhibited cells in a dose-de- MAI-602 decreased the expres- gastric cancer samples and 19 ad- MAI-602 in vitro and in vivo pendent fashion, compared with sion of both GHRH and GHRH-R, jacent normal tissue samples, and To see whether MAI-602 could vehicle used as a control (P less whereas as a GHRH-R agonist found that GHRH-R mRNA was inhibit the growth of gastric can- than .001). increased levels of both the hormone and its receptor. They also demonstrated that PAK1 appears to be a critical mediator of STAT3/ NF-kappaB activity, and that MAI- 602 works primarily by blocking PAK1-mediated inflammatory signaling. “MIA-602 remarkably inhibits the growth of human in vitro and in vivo through the suppression of PAK1–STAT3/NF-kappaB signaling. Our study strongly high- lights the therapeutic potential of GHRH-R antagonists in the treatment of gastric cancer patients. Knowledge gained in our study will shed light on how to select the appropriate patients for personalized cancer therapy using GHRH-R antagonists,” Dr. Schally and his coauthors wrote. The study was supported by the Li Ka Shing Foundation, Chi- nese foundation, and government grants to individual researchers, as well as support from the the Medical Research Service of the U.S. Department of Veterans Af- fairs, South Florida Veterans Af- fairs Foundation for Research and Education, and the University of Miami. Research Funding Opportunity [email protected] The AGA Research Foundation will award over $2 million in research funding to support researchers in gastroenterology and hepatology. FEB. 3, 2017 FEB, 24, 2017 • AGA Investing in the Future • AGA-GRG Fellow Abstract Award Student Research Fellowship (Up to $1,000) ($5,000) • AGA-Moti L. & Kamla Rustgi International Travel Awards ($750) • AGA Student Abstract Award ($1,000)

Apply at www.gastro.org/research-funding.

2750-050RSH_16-7 GIHEPNEWS.COM • FEBRUARY 2017 LIVER DISEASE 29 AGA GUIDELINE Management of acute liver failure BY AMY KARON These include the statement teria, they wrote. Frontline Medical News on Wilson’s disease testing, The guideline conditionally plus suggestions to test and recommends against empirical- hysicians should avoid routinely testing treat patients for herpes sim- ly treating elevated intracranial patients with acute liver failure (ALF) for plex virus (HSV) infection, pressure in ALF, on the basis PWilson’s disease unless there is “high clinical to test pregnant patients for of five randomized trials that suspicion” for the disorder, according to a new hepatitis E virus infection, found no overall mortality ben- guideline from the AGA Institute. and to test for autoimmune efit of moderate hypothermia, Wilson’s disease so rarely accompanies ALF hepatitis. Case series report hypertonic saline, L-ornithine, that a positive test will have low predictive only about a 1% prevalence L-aspartate, intravenous man- value, Steven L. Flamm, MD, of Northwestern of HSV infection in ALF, and nitol, or hyperventilation. University, Chicago, and his associates wrote there is little information The experts cite insufficient in the February issue of Gastroenterology (doi: on diagnostic accuracy or evidence to recommend using 10.1053/j.gastro.2016.12.026). Diagnosing Wil- treatment in this setting, the N-acetyl cysteine in patients son’s disease also is unlikely to change treatment guideline states. Although whose ALF is not associated “because liver transplantation is the ultimate acyclovir is relatively safe and Dr. Steven L. Flamm with acetaminophen exposure. outcome,” they emphasize. inexpensive, data on efficacy Likewise, they find few data to This is 1 of 11 recommendations in the guide- are limited to “a suggestion on a case-report level make any recommendation about using extracor- line, which attempts to reconcile “many areas of that patients with acute hepatitis secondary to HSV poreal liver support systems outside clinical trials. controversy” in diagnosing, predicting outcomes, do better with treatment than without.” Although such systems can “potentially” buy time and managing ALF. Given the relative lack of ran- The guideline also conditionally recommends for patients to either spontaneously recover with- domized controlled trials, they make only one against routine testing for varicella zoster virus out transplant or survive longer on the transplant strong recommendation – to use N-acetyl cysteine and routine liver biopsy in ALF. The authors note list, three systematic reviews found “no clear effect in patients with acetaminophen-associated ALF. only about 10 case reports of varicella zoster–as- on mortality,” and randomized trials reported ei- This guidance is based on three trials that yielded sociated ALF and few data on how liver biopsy ther null results or a “marginally significant surviv- a “marginally significant mortality benefit with results in ALF alter treatment plan, outcome, or the al benefit” in the face of steep costs and potentially N-acetyl cysteine in conjunction with relatively mi- choice to seek liver transplantation. The experts significant toxicities, the authors emphasize. nor toxicity,” they state. do recommend prognostic scoring with Model There were no relevant financial disclosures. The guideline grades seven recommendations as for End-Stage Liver Disease, which analyses have “conditional” based on “very-low” quality evidence. found to be more sensitive than King’s College Cri- [email protected] CMS nixes Part B drug payment demonstration

BY GREGORY TWACHTMAN The demonstration project was physicians and other clinicians in de- tices would have been divided into Frontline Medical News designed to test new methods to livering high quality care,” according two groups. A control group would “improve how Medicare Part B pays to a fact sheet published in March. continue to be paid for Part B drugs controversial demonstration proj- for prescription drugs and supports Under the project, medical prac- Continued on following page Aect that would have tested new methods to pay for the drugs administered in medical offices has been canceled by the Centers for Medicare & Medicaid Services. The agency received considerable backlash from physicians, Congress, and others when the demonstration project was announced in March 2016. “After considering comments, CMS will not finalize the Medicare Part B Drug Payment Model during this administration,” the agency said in a statement. “The proposal was intended to test whether alternative drug payment structures would improve the quality of patient care and the value of Medicare drug spending.” The agency said it received “a great deal of support from some” for the proposed demonstration. However, “a number of stakeholders expressed strong concerns about the model. While CMS was working to address these concerns, the complexity of the issues and the limited time available led to the decision not to finalize the rule at this time.” 30 PRACTICE MANAGEMENT FEBRUARY 2017 • GI & HEPATOLOGY NEWS

Continued from previous page PRACTICE MANAGEMENT TOOLBOX: at the current rate of 106% of average sales price (ASP), while Building a cancer genetics the other would have been paid at 102.5% of ASP plus a flat fee of and prevention program $16.80 per drug payment. Starting in January 2017, each group would BY XAVIER LLOR, MD, PHD testing supported by the refinement

have been further subdivided with hinkstock of the clinical criteria suggestive of a portion of each being subjected Gastroenterologists offer more these syndromes as well as the clear to value-based purchasing tools. than just high-quality colonosco- improvement in outcomes as a result

One key criticism of the demon- / t anttohoho py for colon cancer prevention. of the adoption of cancer preventive stration project centered on the We often are the specialists who measures in mutation carriers.1 In proposed randomization of prac- see a decrease in their drug pay- first recognize a genetic cancer spite of this, genetic testing for col- tices, which was based on primary ments under the proposal, while syndrome during our endoscopy orectal cancer (CRC) syndromes is care service areas (clusters of zip primary care doctors would likely or clinic sessions. The patient not ordered as often as it should be codes with similar Part B medical see an increase, and that 7 of the 10 who piqued my interest in colon according to the prevalence of these care patterns). That randomization drugs most affected by this proposal cancer genetics was a 24-year- syndromes.2 scheme could have caused differ- were drugs used to treat cancer. old woman who was referred In contrast, testing for hereditary ent payment levels – and patient The AGA expressed concern that for postoperative nausea after breast cancer has become more out-of-pocket spending – for geo- many of the drugs that gastroen- a hysterectomy for early-stage generalized, and the threshold for or- graphically close areas. Further, terologists administer would be uterine cancer (that alone should dering genetic testing in the latter is participation in the demonstration included in this proposed new have raised alarm bells). Endos- often lower than for CRC. The are sev- project would have been mandato- payment model and that the model copy revealed (by happenstance) eral reasons for this: 1) much greater ry, with no mechanism to opt out. would affect the patients treated for a stomach coated with polyps. awareness, by both providers and the “This is a model for how Washing- the most complex conditions, such This led to a colonoscopy and di- general public, of hereditary breast ton should, but often doesn’t, work,” as Crohn’s disease and ulcerative agnosis of familial adenomatous cancer conditions; 2) fewer provid- American Medical Association Pres- colitis. Ultimately, this payment polyposis (uterine cancer within ers with expertise in CRC genetics; ident Andrew W. Gurman, MD, said model would limit patient access to FAP is unusual but reported, for 3) lack of a systematic approach to in a statement. “We are grateful that specialist care. The AGA urged CMS those of you studying for boards). identify patients with potential CRC CMS came to the right decision after to include all stakeholders in the de- In 1991, no coordinated genet- syndromes; and 4) absence of a clear listening to stakeholders.” velopment of approaches to control ics program existed within my premorbid phenotype for the most An analysis of the proposed Part B costs. practice so I arranged referrals common of all CRC syndromes, Lynch demonstration project by Avalere to genetic counselors, surgeons, syndrome.3 found that specialists would likely [email protected] and pathologists. This led to the The recent recommendation in discovery of FAP and early stage practice guidelines to screen all (and curable) cancers in her two CRC tumors for Lynch syndrome brothers and her father, in addi- either with immunohistochemistry May 6–9, 2017 tion to extended pedigree analy- to evaluate mismatch repair (MMR) Exhibit Dates: May 7–9 sis that established multi-organ protein expression or through McCormick Place, Chicago, IL cancer risks in other relatives. tandem repeat analysis to test for www.ddw.org Years later, she brought her two microsatellite instability4 has high- adopted children to meet me and lighted that about 10% of all CRCs The First told me of lighting candles in my (a percentage consistently seen & Foremost honor during an American Can- in different ethnic groups5) need GI Event cer Society walk. This is why we further cancer genetic evaluation, in the World. become doctors. and many will require sequencing In this month’s column, Dr. of germline DNA. Although data on Xavier Llor describes the cancer cost-effectiveness of this approach genetics program he and others are somewhat conflicting,6,7 it is have built at Yale. It provides sensible because it is systematic, practical steps that can be taken and studies have shown an increase by health system or community- in diagnostic yield through univer- based gastroenterologists to sal tumor screening.8 Unfortunately, recognize and manage these in practice, often suspicious tumor complex syndromes. We are the testing results are not followed up Revolutionizing GI specialists on the front lines and by cancer genetics referrals, and Access leading-edge Dr. Llor helps us provide the co- many patients with CRC syndrome advances and share insights ordinated care our patients ex- remain undiagnosed. with notable GI experts all in one place: Digestive pect from us. Patients with oligopolyposis Disease Week® (DDW) 2017. (fewer than 100 polyps over time) Returning to Chicago in May, John I. Allen, MD, MBA, AGAF also present diagnostic challeng- DDW teaches attendees Editor in Chief es. Some have attenuated familial novel developments in the REGISTER BY MARCH 22 adenomatous polyposis because of ﬁ elds of gastroenterology, AND SAVE AT LEAST $80. hepatology, GI endoscopy mong all common cancers, an APC mutation or MUTYH-asso- and GI surgery. Don’t miss AASLD, AGA, ASGE and breast and colon have the high- ciated polyposis. Recent findings this must-attend event. Jan. 11, 2017 SSAT members-only registration opens. Aest percentage of cases that are have revealed other less commonly Register online at due to hereditary syndromes. Many mutated genes that also result in General registration www.ddw.org Jan. 18, 2017 opens. of the responsible genes have been oligopolyposis and a significant CRC identified, and the last few years have risk: polymerases POLE and POLD1, seen an increase in uptake of genetic Continued on following page GIHEPNEWS.COM • FEBRUARY 2017 PRACTICE MANAGEMENT 31

Continued from previous page individuals at risk, the complexity ensures their proper attention in versal tumor testing is an effective of caring for these patients de- a longitudinal fashion, making the tool, but other complementary GREM1, MCM9, or NTHL1. Because mands a service that can stand program their home for health approaches such as the use of of the relatively low number of up to the multiple challenges. For care. questionnaires can also contribute polyps in many of these syndromes instance, most CRC syndromes are We integrated in the program, to identifying patients in need for and the lack of a systematic strat- in fact multi-cancer syndromes among others, physician leaders in cancer genetics assessment. egy to add up all polyps diagnosed with an increased risk of cancer gastrointestinal, breast, gynecolog- In our program, the pathology over time, we not uncommonly and other pathologies in different ical, endocrine, and genitourinary department tests for MMR protein fail to suspect some polyposis syn- organs beside the colon. Further- high-risk malignancies; genetic expression in dromes. Furthermore, the mixed more, the psychological implica- counselors; an advanced practice all bowel and pattern of polyps that is often asso- tions of having a heritable cancer registered nurse specializing in endometrial ciated with some of the mentioned condition often take an important cancer prevention and risk re- tumors. The mutated genes adds an extra chal- toll on affected families, with com- duction; and a scientific director ones that have lenge to diagnosing these cases. mon feelings of guilt for having who leads the Clinical Laboratory loss of ex- Once individuals with CRC syn- passed the mutated genes to the Improvement Amendments–certi- pression of an dromes are identified, the challenge offspring. fied laboratory at Yale that offers MMR protein is to provide them with the care Thus, for the best care to be in-house genetic testing, including are reported that they need, because many gas- provided to affected families, full-exome sequencing. The SCGPP to the SCGPP, troenterologists, oncologists, and there is a tremendous need for was started in July 2015, and it DR. LLOR which contacts other health care providers are not well-organized and comprehen- currently provides more than 250 the patient’s extremely familiar with the current sive cancer genetics services that new consultations per month. providers to request a referral. In options for these patients. are capable of responding to the The following are several key a relatively short implementation In summary, there is a need to multiple needs of these families elements that I consider important time, this has already resulted in find systematic ways to triage and so state-of-the-art cancer pre- for a cancer genetics program and a significant increase in the num- appropriately refer patients with ventive measures can be carried how they have been addressed at ber of patients referred for cancer a potential CRC syndrome to can- out and multilevel support can be the SCGPP. genetics consultation and new cer genetics specialists so patients provided. The mentioned consid- Lynch syndrome diagnosis. On the and their families can benefit from erations were the guiding force in Identification through other hand, two brief and sim- proper diagnosis and cancer pre- the creation of the Smilow Cancer risk stratification plified questionnaires have been ventive measures. Genetics and Prevention Program Because the identification of all developed and distributed in clin- (SCGPP) at Yale. Thus, we estab- individuals who can benefit from ics, one for health providers and Building a comprehensive lished a comprehensive program cancer genetics consultation is one administered directly to pa- cancer genetics program that brings together health pro- complex yet essential, a compre- tients. The questionnaires contain Although implementing systemat- fessionals specializing in different hensive approach with different questions related to the patient’s ic approaches is key to selecting aspects of these patients’ care that strategies is often necessary.9 Uni- Continued on page 33

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PROFESSIONAL OPPORTUNITIES

Albuquerque, NM Presbyterian Healthcare Services of New Mexico is actively seeking BE/BC Gastroenterology physicians to join our existing group of 10 physicians and 8 advanced practitioners. PHS is seeking a provider that is advanced endoscopy trained and can perform ERCP/EUS procedures. Presbyterian Medical Group employs over 700 physicians representing over 50 specialties. Presbyterian Hospital is a 453 bed tertiary care center. Enjoy over 300 days of sunshine, a multi-cultural environment and casual southwestern lifestyle. It is also home to University of NM, a world class university. Physician benefits: This opportunity offers a competitive salary; sign-on bonus, relocation; CME allowance; 403(b) w/match; 457(b); health, life, AD&D, disability ins, life; dental; vision, occurrence type malpractice ins, etc. EOE. For more information contact: Kelly Herrera, PHS, PO Box 26666, ABQ, NM 87125 [email protected] tel: 505-923-5662 fax: (505) 923-5007 You may also apply on-line at www.PHS.org www.phs.org

WHERE A LANDSCAPE OF OPPORTUNITIES AWAITS A Gastroenterology FACULTY Position Georgia GASTROENTEROLOGIST AUGUSTA UNIVERSITY Medical College of Georgia, Augusta, GA Gundersen Health System in La Crosse, Wisconsin Th e Digestive Health Center/GI Division of the Department of Medicine is seeking a BC/BE Gastroenterologist to join its invites applications for faculty positions at the Asst/Assoc. Prof. level. Physicians with expertise in General Gastroenterology, Advanced established medical team. Endoscopy, Infl ammatory Bowel Disease, Motility and Hepatology Practice in our state-of-the-art Endoscopy Center are requested to apply. BC IM/GI required. and modern outpatient clinic. Outreach services are Desired candidates will: participate in patient care and teaching, work provided at our satellite clinics located within an collaboratively with leadership in expanding the Division into a new, easy drive from La Crosse. In addition, you will have 44,000 sq. feet, dedicated, state-of-the art Digestive Health Center and opportunities for clinical research and will be Transitional Research Center; and develop basic, clinical or translational actively involved in teaching our Surgical, research programs. Augusta University is a thriving academic environment, Transitional, and Internal Medicine residents. and qualifi ed candidates will have opportunities at the Director level. Outstanding facilities and support are available to initiating clinical trials You’ll join a physician-led, not-for-profit health and building innovative clinical programs. Established Centers and system with a top-ranked teaching hospital and Institutes provide superb opportunities for collaborative translational and one of the largest multi-specialty group practices basic research. A competitive salary and incentive plan rewards clinical with about 700 physicians and associate medical productivity and research funding. staff. Visit gundersenhealth.org/MedCareers To apply for this position, please BQQMZWJBPVSwebsite at: Send CV to Kalah Haug www.augusta.eduISKPCTGBDVMUZ AND submit CV with a brief Medical Staff Recruitment summaryof interests to: Satish SC Rao, MD, PhD, Chief, Division of Gastroenterology/Hepatology. [email protected]. Gundersen Health System [email protected] Augusta University is an Equal Opportunity/ADA/Affi rmative Action, or call (608)775-1005. and Equal Access Employer. Augusta University has a strong interest in promoting diversity in its faculty and women and minority candidates are

encouraged to apply. 278432

EEO/AA/Veterans/Disabilities Moving? Look to Classiﬁ ed Notices for practices available in your area. GIHEPNEWS.COM • FEBRUARY 2017 PRACTICE MANAGEMENT 33

Continued from page 31 Because education of health care witnessed changes at different Finally, the increasing number providers about these conditions levels around genetic testing of commercial laboratories offer- own cancer history, polyp history, is essential to foster collaboration that are having a tremendous ing genetic testing has resulted in cancer screening tests, and fam- and to help them better understand impact. Some of these changes more competition and lower pric- ily history. The first one assists about cancer risk assessment, ge- pose significant new challenges es, in some cases to a point that health care providers in identify- that require rapid adaptation on direct-to-consumer charges may ing individuals. The second one is We are quickly moving from the providers’ side. Thus, we are be even lower than insurance co- completed by patients, collected, quickly moving from single gene payments. This is contributing to and reviewed by a genetic coun- single gene testing to panels testing to panels of genes tested a rapid increase in individuals be- selor. Suitable patients are invited of genes tested at once. This at once. This has resulted in unex- ing tested including patients who to a cancer genetics consultation pected findings such as mutated otherwise would unlikely have through their primary health care has resulted in unexpected genes not initially suspected or been tested in the past because providers. A third questionnaire findings such as mutated variants of unknown significance of lack of fulfillment of insurance directed to endoscopy services genes not initially suspected. that often should be interpreted criteria. The challenge for us is will be rolled out soon. This colin the context of the personal and to be ready to help navigate the lects information on completed family history of cancer because increasing amount of information endoscopy procedures, polyps and netics, and what the SCGPP can of the lack of definite information obtained as a result of all these cancers found, and family history. offer to some of their patients, ses- on their potential pathogenicity.10 changes. The program is currently work- sions are routinely held with some Adding to that, genome-scale ing with information technology of them to discuss different aspects tumor sequencing is becoming Integration of electronic platforms to develop a system to pull from on cancer genetics. more common as it increasingly In an era of full implementation of the electronic medical record In summary, a comprehensive informs on the types of anti-tumor EMRs, a cancer genetics program (EMR) relevant information on and coordinated approach is key to therapies to be selected for a spe- should not simply adapt to the the patient’s own medical histo- substantially expand the number of cific patient (precision medicine). new environment but fully em- ry, family history, and endoscopy individuals identified and referred This approach is revealing some brace it and explore the possibili- findings. A set of criteria has been for cancer genetics assessment. unexpected information because in ties that come with it. Thus, from established so relevant informa- some cases it has helped identify its inception, the SCGPP has been tion will generate an alert for Genetic testing significant mutations in the germ- embracing the electronic plat- prompt referral for the SCGPP. During the last few years we have line.11 Continued on following page CLASSIFIEDS Also available at MedJobNetwork.com

PROFESSIONAL OPPORTUNITIES

Gastroenterology Physician needed for North Dakota

North Dakota—This major not-for-profit Health System is a fully integrated healthcare system serving northwest/central North Dakota and Eastern Montana. With a tertiary care hospital of 251 beds, close to a dozen rural health clinics and a long-term care facility, this healthcare system provides a full complement of healthcare services to the region. This healthcare system’s NorthStar Criticair helicopter provides critical care transport within a 150-mile radius and is a verified Level 2 Trauma Center. • Hospital Employed • Base Salary - $640,000 • Over Production Incentive • Signing Bonus - $50,000 • Full Benefits If you’re looking for great quality of life within a city with excellent family values, this city has it all. Please call Robert Overfield at 800-839-4728 or email your CV to [email protected] 34 PRACTICE MANAGEMENT FEBRUARY 2017 • GI & HEPATOLOGY NEWS

Continued from previous page appointments for GI patients with tions to facilitate all these services Progeny suite that incorporates the genetic counselor and the phy- and help engage providers in the not only clinical and pedigree forms to the maximum extent so sician leader cover all different as- corresponding facilities. She reg- building components but also the the clinical operation is stream- pects of care, and a complete plan ularly attends tumor board meet- genotype and sample manage- lined and documentation is well is suggested and discussed. Once ings in the local hospitals to help ment systems (LAB and LIMS). displayed and accessible in the the initial assessment is finalized disseminate knowledge in cancer Thus, a fully searchable and ro- EMR. The Yale health care system and genetic testing results (if or- genetics as well as to assist in the bust database and biological sam- uses EPIC (Epic Systems, Verona, dered) are completed, patients are identification of patients who can ple repository have been created, Wisc.) as its EMR, and the SCGPP followed prospectively to ensure benefit from referral to the SCGPP. and all patients are approached uses Progeny (Progeny Genetics about participating in this insti- LLC, Delray Beach, Fla.) to collect tutional review board–approved data, construct family pedigrees, registry. and build the research registry of Take-away points: the Program. A joint effort by the 1. GI cancer genetics is becoming more complex and there is an Cancer prevention in nonfamilial, developers of both systems has increasing need for comprehensive and integrated services to help nonsyndromic cases resulted in integration at different identify and care for families affected by hereditary GI cancers. Some nongenetic factors such levels. 2. A multifaceted approach is needed to increase identification and as diet, physical activity, or toxic Thus, after a referral is re- care for these families. exposure seem to underlie the ceived, patients are called, 3. There is an opportunity for electronic platforms to help improve important differences seen in CRC registered, and asked several the care of these families. incidence around the world.12 questions including their own Thus, interventions at this level cancer and polyp history as well can potentially have a very high as their family history of cancer. that prophylactic and cancer pre- Surveillance and recall program impact for cancer prevention in all This assists in triaging patients vention measures are undertaken Key to the success of a cancer ge- individuals. In fact, even individ- to the most appropriate SCGPP according to the updated stan- netics program is successfully co- uals with genetic mutations that provider: a genetic counselor, dards of care. Complex cases are ordinating care so preventive tests carry a high risk for developing a disease physician leader, or a discussed with the entire team in and measures are performed to malignancies can see their risk combined visit according to the the weekly case conference that decrease cancer risk. The SCGPP modified by addressing lifestyle/ established internal protocol. is always followed by a scientific aims to be the home for familial In all cases, for new patients conference with alternating top- and hereditary cancer patients. with GI cancer syndromes, a com- ics such as journal club, practice For these patients, this implies Key to the success of a bined appointment of a genetic improvement, ongoing research a strong commitment to their cancer genetics program is counselor and the GI physician projects, and extensive case re- needs, with a special emphasis on leader is scheduled. At the same views. the appropriate prophylactic and successfully coordinating time, patients are sent an email cancer surveillance measures. care so preventive tests and with a link to the Progeny online Network integration The registry database provides measures are performed to questionnaire that includes per- Although the needs for cancer an extremely useful tool to track sonal and family history of cancer genetics can be found in any cor- scheduled tests and procedures decrease cancer risk. as well as extensive clinical infor- ner of the map, it is not realistic and to generate reminders. The mation. Once the questionnaire is to believe that services like this advanced practice registered nurse completed, the program generates can be provided in a consistent meticulously follows them and environmental factors.13 a preliminary pedigree that pa- fashion without being part of a ensures proper completion and re- Therefore, the SCGPP has created tients can print, and the SCGPP bigger program umbrella. In our view. She follows up on the sched- tools for assessment and risk strat- gets a message communicating case, Yale’s Smilow Cancer Center uling of the specific tests, reviews ification that take the mentioned that the patient has completed this charged the SCGPP with the duty results once these tests are com- factors into account and create a questionnaire. Therefore, when to provide high quality and con- pleted, and brings them back to dis- roadmap for primary prevention. patients are seen on consultation, sistent cancer genetics services to cussion with the physician leader. The tools include questionnaires providers already have the provi- the entire network that currently She also follows up on incomplete on all environmental exposures, sional data and pedigree. During includes a total of 5 affiliated hos- tests and helps to bring down po- lifestyle factors, and medications the visit, information is verified pitals and 10 care centers. tential barriers in the performance the patient is exposed to and that and edited as needed, and the fi- For this to happen, all cases of these tests. Another key aspect can influence cancer risk. The in- nalized pedigree goes live through seen outside the main campus of her job consists of facilitating the formation is reviewed in a special a hyperlink in the EMR. Every revi- are brought up for discussion assistance of psychological support clinic session, and all services to sion results in an updated pedigree in the weekly case conference. or risk reduction through lifestyle help modify risk factors are offered visible through the mentioned Furthermore, counselors dis- changes, such as smoking cessation to the patient. hyperlink. This process saves a tributed throughout the network or weight reduction, to patients in considerable amount of time to routinely also see patients in the need of such services. Conclusions the providers and increases clinic main office, and when away, they There is a clear need for GI cancer efficiency. participate in case conference and Cancer genetics research genetics services to reach all pa- Informed consent for the re- scientific conference via telecon- Key to an academic program in tients who can benefit from them, search registry is also fully elec- ference or videoconference. All cancer genetics like this one is and at the same time the field is tronic, with signatures recorded this is considered critical to facil- to facilitate the study of familial rapidly growing in complexity. in tablets that transmit the signed itate a cohesive and state-of-the- and syndromic cancers, includ- More than ever, these services document to a secure server. art program that extends beyond ing aspects such as phenotype demand a multidisciplinary ap- the main campus. characterization or the efficacy proach, with experts leading the The necessary team approach Recently, telemedicine is used to of chemopreventive approaches. care of these patients in a coordi- Another essential component of a provide consultations directly to To accomplish this, a patient reg- nated fashion with the rest of the cancer genetics program like this patients so the program’s services istry is essential. Registries are health care community. However, is the integrated and comprehen- are brought to the most remote lo- extremely useful tools that facili- payers have not fully recognized sive approach to patients. Thus, cations. A senior genetic counselor tate data accrual and analysis. The these complexities, and some in our Program, the combined is in charge of the network opera- SCGPP registry is based on the Continued on following page GIHEPNEWS.COM • FEBRUARY 2017 PRACTICE MANAGEMENT 35

Continued from previous page with colorectal cancer. JAMA. 2012;308:1555-65. tic yield of clinical tumor and germline whole-ex- carriers of hereditary colorectal cancer: a pro- 9. Stoffel E.M., Kastrinos F. Familial colorectal ome sequencing for children with solid tumors. spective investigation in the CAPP2 study. J Clin critical aspects, such as genetic cancer, beyond Lynch syndrome. Clin Gastroen- JAMA Oncol. 2016;(Epub ahead of print). Oncol. 2015;33:3591-7. counseling services, are not al- terol Hepatol. 2014;12:1059-68. 12. Aleksandrova K., Pischon T., Jenab M., et al. ways properly reimbursed. As we 10. Desmond A., Kurian A.W., Gabree M., et al. Combined impact of healthy lifestyle factors on Dr. Llor is in the department of med- shape up the present and future Clinical actionability of multigene panel testing colorectal cancer: a large European cohort study. icine and cancer center, Yale Univer- of health care, which should be for hereditary breast and ovarian cancer risk as- BMC Med. 2014;12:168. sity, New Haven, Conn. He discloses fully personalized and patient sessment. JAMA Oncol. 2015;1:943-51. 13. Movahedi M., Bishop D.T., Macrae F., et al. no conflicts of interest. centered on addition to embrac- 11. Parsons D.W., Roy A., Yang Y., et al. Diagnos- Obesity, aspirin, and risk of colorectal cancer in ing new ways of delivering it, we need to engage all the players and help them understand what this takes and the rewards in the form of better outcomes that will come with it.

References 1. Kastrinos F., Stoffel E.M. History, genetics, and strategies for cancer prevention in Lynch syndrome. Clin Gastroenterol Hepatol. 2014;12:715-27 (quiz e41-e43). 2. Karlitz J.J., Hsieh M.C., Liu Y., et al. Popula- tion-based Lynch syndrome screening by microsatellite instability in patients

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