VOL. 8 NO. 10 OCTOBER 2014 ® Herbal-supplement liver injuries on the rise for 10 years Used for bodybuilding and weight loss. BY MICHELE G. Wally Reeves SULLIVAN Dr. Trevor J. Royce said a “sizable proportion of the U.S. population who have less than a 9-year life expectancy” had cancer screening. Unnecessary cancer screening in U.S. Frontline Medical News A substantial proportion of older adults in the United States undergo unnecessary and even harmful screening for colon, prostate, breast, and cervical cancer, contrary to clear guidelines that are widely recognized and well publicized, according to two separate studies published online in JAMA Internal Medicine. In the case of colon cancer, most of these unnecessary screenings can be attributed to patients getting rescreened more frequently than at the 10-year intervals recommended, and continued screening past the age of 75 years is also a culprit. With the other cancers, the main reason for these unnecessary procedures is continuing screening in patients who have a short life expectancy because of advanced age or irreversible health problems. In both reports, the investigators emphasized that unnecessary cancer screening not only is inefcient but is also harmful for individual patients because it exposes them to invasive procedures and complications, impairs their quality of life, and sometimes leads to downstream overdiagnosis and overtreatment of cancers that would have remained asymptomatic until the See Unnecessary · page 21 GI & HepatoloGy News 151 Fairchild Ave., Suite 2, Plainview, NY 11803-1709 BY MARY ANN MOON Frontline Medical News S erious liver injury from herbal and dietary supplements – including those used by bodybuilders – has risen signifcantly over the past decade. According to fndings from a review, herbal supplement–related injuries increased from 2% to 20% of all nonacetaminophen drug–related liver injuries. Injuries from bodybuilding supplements rose from 2% to 8%, while those related to nonbodybuilding supplements increased from 5% to 12%, Dr. Victor J. Navarro, chair of the hepatology division at the Einstein Medical Center, Philadelphia, and his coauthors reported in the September issue of Hepatology (2014 Aug. 25 [doi: 10.1002/hep.27317]). The investigators reviewed 839 cases included in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2013. Of these, 709 were caused by nonacetaminophen medications, 85 by nonbodybuilding supplements, and 45 by bodybuilding supplements. Overall, the injuries from supplements rose from 7% to 20%. Those related to See Supplement · page 6 I N S I D E News Poor stewardship Redundant IV antibiotics found in 80% of hospitals. • 5 IBD and Intestinal Disorders Freston Conference coverage Several presentations were covered; Dr. David T. Rubin, course director, comments. • 22 Endoscopy, Pancreas & Biliary Tract Cholecystectomy after RYGB Overall rates are low; routine removal not recommended. • 30 AGA Spring Postgraduate Course Learn the latest Moderators describe this year’s presentations. • 32 Pill holds promise for C. diffcile BY ALICIA AULT Frontline Medical News WASHINGTON – A rationally designed microbiome-based pill successfully eradicated recurrent Clostridium difcile infection in 29 of 30 patients in a study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Preliminary data were presented at the 2014 James W. Freston Conference sponsored by the American Gastroenterological Association in August. The patients in the phase I/II study were divided into two separate 15-patient cohorts and were given two diferent dose levels of the therapy, SER-109. The drug contains spores from gram-positive bacteria that are taken from stool and then purifed to kill the vegetative bacteria, said David Cook, Ph.D., executive vice president and chief scientifc ofcer of Cambridge, Mass.–based Seres Health. The therapy appears to See Pill · page 22 CHANGE SERVICE REQUESTED Presorted Standard U.S. Postage PAID Permit No. 384 Lebanon Jct. KY NEWS 2 O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S CLINICAL CHALLENGES AND IMAGES What’s your diagnosis? A 28-year-old Vietnamese man without any signifcant past medical history presented with 6 months of epigastric pain without nausea, vomiting, fevers, weight loss, or other symptoms. Physical examination was normal, as were laboratory tests, including a complete blood count, liver function tests, and chemistry panel. Proton pump inhibitor therapy was administered for 2 months without any improvement in symptoms. Esophagogastroduodenoscopy was subsequently performed and revealed a 3.5 × 2.5-cm submucosal bulge at the gastroesophageal junction (Figure A). Biopsy with cold forceps elicited persistent extravasation of a thin white fuid (Figure B). Histology was indeterminate, and Gram stain, acid-fast bacilli, and cultures were negative. After endoscopy, computed tomography of the abdomen/pelvis revealed a 3.6 × 2.7 × 2.5-cm enhancing perigastric lesion adjacent to a normal-appearing pancreas without lymphadenopathy (Figure C). AGA InstItute By Dr. Sun-Chuan Dai and Dr. Audrey Calderwood. Published previously in Gastroenterology 2012;142:1072, 1258, 1259. The diagnosis appears on page 30. [email protected] Physicians in group practice setting make more BY GREGORY TWACHTMAN Frontline Medical News P hysicians in medical groups and other organized systems of care delivery saw a slight increase in compensation, according to annual survey data released by the American Medical Group Association. In general, fndings show average percentage increases in compensation in 2013 were slightly higher than in 2012, with the overall weighted average increase in 2013 being 2.9%, up from 1.6% in the previous year. Results were based on a survey conducted on behalf of the Medical Group Management Association (MGMA) by Sullivan, Cotter and Associates, with 289 medical groups representing about 73,700 providers submitting valid survey responses. Individual specialties showing the biggest median total compensation increase year over year include gastroenterology (a 9.0% increase to in ChiEf Colin W. Howden, M.D., AGAF Editor AssoCiAtE Editors Joel V. Brill, M.D., AGAF Barbara H. Jung, M.D. John A. Martin, M.D. Kevin D. Mullen, M.D., FRCPI David T. Rubin, M.D., AGAF Editor EmEritus Charles J. Lightdale, M.D., AGAF AGA institutE stAff Managing Editor Brook A. Simpson Special Content Editor Lindsey M. Brounstein Publications Coordinator Jillian L. Schweitzer Vice President of Publications Erin C. Dubnansky offiCErs of thE AGA institutE President John I. Allen, M.D., MBA, AGAF President-Elect Michael Camilleri, M.D., AGAF Vice President Timothy C. Wang, M.D., AGAF Secretary/Treasurer Francis M. Giardiello, M.D., AGAF AGA Research Foundation Chair Martin Brotman, M.D., AGAF Past President Anil K. Rustgi, M.D., AGAF ©2014 by the AGA Institute. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. $471,336), cardiac/thoracic surgery (8.2% to $569,073), emergency medicine (5.2% to $316,739), and neurology (5.1% to $268,096). Total compensation includes the total compensation of the individual provider, including base, variable, and administrative compensation, plus all voluntary salary reductions. Four specialties saw compensation decreases during this time period, including allergy/immunology (a 1.3% decrease to $267,338), rheumatologic disease (–0.5% to $239,112), cardiology- Gi & hEpAtoloGy nEws is the offcial newspaper of the American Gastroenterological Association (AGA) Institute and provides the gastroenterologist with timely and relevant news and commentary about clinical developments and about the impact of health care policy. Content for Gi & hEpAtoloGy nEws is developed through a partnership of the newspaper’s medical board of editors (Editor in wChief and Associate Editors), Frontline Medical Communications Inc. and the AGA Institute Staff. “From the AGA” is provided exclusively by the AGA, AGA Institute, and FDHN. All content is reviewed by the medical board of editors for accuracy, timeliness, and pertinence. To add clarity and context to important developments in the feld, select content is reviewed by and commented on by external experts selected by the board of editors. The ideas and opinions expressed in Gi & hEpAtoloGy nEws do not necessarily refect those of the AGA Institute or the Publisher. The AGA Institute and Frontline Medical Communications Inc. will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein. Advertisements do not constitute endorsement of products on the part of the AGA Institute or Frontline Medical Communications Inc. POSTMASTER Send changes of address (with old mailing label) to GI & Hepatology News, Subscription Service, 151 Fairchild Ave., Suite 2, Plainview, NY 118031709. The AGA Institute headquarters is located at 4930 Del Ray Avenue, Bethesda, MD 20814, [email protected]. Editorial Offces 5635 Fishers Lane, Suite 6100, Rockville, MD 20852, 240-221-2400, fax 240-221-2548 Gi & hEpAtoloGy nEws (ISSN 1934-3450) is published monthly for $230.00 per year by Frontline Medical Communications Inc., 7 Century Drive, Suite 302, Parsippany, NJ 07054-4609. Phone 973-206-3434, fax 973-206-9378 Scan this QR Code to visit gihepnews.com cath lab (–0.4% to $544,733), and endocrinology (–0.2% to $233,769). Overall, AMGA reported that 68% of specialties reported increases in compensation in 2013, with primary care specialists reporting a 3.8% increase in 2013, up from 2.8% in 2012. Other specialists saw compensation increase on average 1.8%, up from 1.6%, and surgical specialists saw an average increase of 3.0%, up from 0.5%. [email protected] frontlinE mEdiCAl CommuniCAtions soCiEty pArtnErs Director, FMC Society Partners Mark Branca Editor in Chief Mary Jo M. Dales Executive Editors Denise Fulton, Kathy Scarbeck Managing Editor Lora T. McGlade Creative Director Louise A. Koenig Print Production Manager Rebecca Slebodnik Display Advertising Sales Representative James G. Pattis, 201-767-4170, fax 201-767-2784, [email protected] Senior Director of Sales Tim LaPella, 484-921-5001, [email protected] Classifed Sales Representative Linda Wilson 973-290-8243, [email protected] Advertising Offces 7 Century Drive, Suite 302, Parsippany, NJ 07054-4609 973-206-3434, fax 973-206-9378 FRONTLINE MEDICAL COMMUNICATIONS Stephen Stoneburn, Chairman Douglas E. Grose, EVP Digital Business Development/CFO Marcy Holeton, President/CEO, Clinical Content Division Alan J. Imhoff, President/CEO, Medical News Division JoAnn Wahl, President, Custom Solutions, 973-206-8989 [email protected] Jim Chicca, Executive Director, Operations Jim McDonough, VP, Marketing & Customer Advocacy Carol Nathan, VP, Custom Programs Lori Raskin, Corporate Director, Research & Communications Donna Sickles, Corporate Director, Audience Development Subscription Inquiry Line 1-800-480-4851 In affliation with Global Academy for Medical Education, LLC. Sylvia H. Reitman, MBA, Vice President, Medical Education & Conferences David J. Small, MBA, Vice President, Events GIHEP_3.indd 1 9/12/2013 1:31:52 PM NEWS 4 O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S CMS website snafu could lead to penalties for some BY ALICIA AULT Frontline Medical News irst-time meaningful use participants who are using older technology, but who did not get a hardship F exemption by July 1, will see their Medicare pay reduced 1% in 2015. Because of a confuence of factors, a certain subset of physicians who engaged in meaningful use for the frst time this year will not be able to attest to their participation by the Oct. 1 deadline set by the Centers for Medicare & Medicaid Services – and thus, will be penalized. “Physicians are not only frustrated, but perhaps reaching despondency on the topic,” Dr. Steven J. Stack, president-elect of the American Medical Association, said in an interview. Overall, about half of physicians had not participated in meaningful use as of the beginning of this year. Theoretically, all of them could face the 1% reduction in Medicare pay, though it’s likely that a smaller subset will, Dr. Stack said. Those who did not meet meaningful use criteria in 2013 and who anticipated that they would not do so again in 2014 could have applied for a hardship exemption by July 1 to avoid a penalty in 2015. Physicians who were starting on the meaningful use process for the frst time in 2014 also had until July 1 to apply for that exemption. After determining that many vendors did not have 2014 software ready for physicians, CMS proposed in late May to give all meaningful users more fexibility. Physicians were told they could use either a 2011 version, a 2014 version, or some combination, and not be penalized in 2015. That proposal was made fnal in late August. Applying for that fexibility will be done via the CMS website, which is slated to be ready a few weeks after Oct. 1. But frst-time meaningful use participants must make their attestation to the CMS by Oct. 1. The bottom line is that frst-time participants who are using older technology and did not get the exemption will be penalized. A CMS spokesman said that they could still receive an incentive payment for 2014 – if they go online in mid-October and apply for the fexibility option. But Dr. Stack called that little consolation. It is as if the CMS took away $100 of a $1,000 pot and said that there was still $900 left, he said. Thom Kuhn, a staf member at the American College of Physicians, also said that the CMS explanation was not good enough. “Failure to have a system ready by the time a fnal rule is issued is a management failure,” said Mr. Kuhn, in an interview. Meanwhile, two members of Congress – Rep. Renee Ellmers (R-N.C.) and Rep. Jim Matheson (D-Utah) – have called on the CMS to extend that Oct. 1 deadline. Their legislation would provide “an administrative delay” for those attempting to attest to meaningful use for the frst time in 2014. [email protected] On Twitter @aliciaault NEWS GIHEP NEW S. COM • OCT OBE R 2014 5 Redundant antibiotics used at 80% of hospitals BY JENNIE SMITH Frontline Medical News R edundant combinations of intravenous antibiotics are used in nearly 8 of 10 hospitals, even though they are very infrequently indicated, said a group of researchers working to promote antimicrobial stewardship in hospitals. Leslie Schultz, R.N., Ph.D., of Premier Safety Institute in Charlotte, N.C., and colleagues reported that a review of cases from more than 500 U.S. hospitals revealed that about 150,000 days of inappropriate antibiPeople are not as aware as they need to be about what antibiotics kill what bacteria. DR. SRINIVASAN otic therapy were prescribed, at an estimated excess cost of more than $12 million over the 4-year study period. Some 78% of hospitals in the study used the unnecessary drug combinations, they said. The combination of metronidazole and piperacillin-tazobactam accounted for more than half of the redundant treatments detected in the study, with some 32,500 cases receiving this combination for 2 days or more. Other commonly seen redundant treatments included metronidazole and ampicillin-sulbactam, along with metronidazole and ertapenem, which, together with the metronidazole and piperacillin-tazobactam combination, were seen as responsible for 70% of redundant treatments administered to patients (Infect. Control Hosp. Epidemiol. 2014;35:1229-35). In a telephone press conference, one of Dr. Schultz’s coauthors on the paper, Dr. Arjun Srinivasan of the Centers for Disease Control and Prevention, Atlanta, said that, while concerns about antimicrobial stewardship are not new, the fndings came as a surprise. “We would expect the use of these combinations to be vanishingly rare given how often they’re indicated,” Dr. Srinivasan said, citing a lack of training in antibiotics as a contributing factor. “We’ve heard from a lot of clinicians that providers don’t know that piperacillin-tazobactam very efectively kills anaerobic bacteria – but they do know that metronidazole is efective,” Dr. Srinivasan said. “Peo- ple are not as aware as they need to be about what antibiotics kill what bacteria, and we need to make sure people know which antibiotics need to be combined and when – and that with some, you don’t gain anything by adding the second drug. You only increase the risk of side efects.” Another physician taking part in the press conference, Dr. Sara Cosgrove of Johns Hopkins Hospital, Baltimore, agreed. “We have subopti- mal training among medical students and house staf about what antibiotics cover what bugs,” she said. “We have seen publications suggesting that medical students and residents Continued on following page NEWS 6 O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S Beware: Labels can lie Supplement from page 1 nonbodybuilding supplements increased from 5% to 12%, and those from bodybuilding supplements from 2% to 8%. There were no transplants or deaths among those with bodybuilding supplement–related injuries. These occurred exclusively in men and were characterized by prolonged jaundice. Injuries from nonbodybuilding supplements occurred most often in middle-aged women (65%). Among these, there were 11 transplants and four deaths; one of these was a patient who died after transplant. Two of the other deaths were related to a cholestatic or mixed injury, and one resulted from a comContinued from previous page want more info on antibiotics.” Dr. Cosgrove also noted that changes in hospital work practices may have contributed to the problem. “More people are working in hospitals on shorter shifts, and there are communication issues from one physician to the next. One physician may start an antibiotic, and a second physician starts a second. There are many ways we can address the problem of unintended duplicate therapy,” she said, including the use of alerts generated when the pharmacy receives a request for a redundant drug. Dr. Srinivasan said that plication of endoscopy. Most patients were using multiple supplements, which included multiple ingredients (vitamins, minerals, and botanical extracts). The entire group of 130 patients had taken a total of 217 such products. Among these, 12% of the bodybuilding supplements and 22% of the nonbodybuilding supplements were labeled as having a single ingredient. However, 10% of the bodybuilding and 13% of the nonbodybuilding supplements had at least 20 ingredients. It’s nearly impossible to identify the specifc culprit ingredients, wrote Dr. Navarro and his coauthors. hospitals that have implemented alerts have found them efective. Still, both physicians stressed that whatever the methods used, dedicated antimicrobial stewardship teams in hospitals were essential to ensuring the avoidance of redundant treatments. “Many hospitals report that they are thinking about having an antimicrobial stewardship program. We’d like to nudge them into actually have one,” said Dr. Cosgrove, who is chair of the antimicrobial stewardship committee for the Society for Healthcare Epidemiology of America, which publishes Infection Control and Hospital Epidemiology. Though Johns Hopkins “The numerous products that frequently contain multiple ingredients, often with unclear chemical descriptors and variable common names, can confound pinpointing the specifc toxic agent. Sometimes, such supplements are contaminated with microbials, drugs, mycotoxins, and heavy metals. DR. NAVARRO Furthermore, some products may seem quite innocuous, such as multivitamins, making it difcult to conceive of any toxic potential.” Sometimes, such supplements are has had an antimicrobial stewardship team since 2002, most hospitals do not have formal groups in place, she said. The Society for Healthcare Epidemiology of America will publish checklists and guidelines in 2015 to help hospitals set up teams, Dr. Cosgrove said, noting that California has recently passed legislation mandating their creation in all hospitals in that state. All the coauthors of Dr. Schultz’s study except Dr. Srinivasan are employees of Premier, which is a for-proft research corporation. Dr. Srinivasan reported having no fnancial conficts of interest. [email protected] Physician income: Least in the East BY LUCAS FRANKI Frontline Medical News B oth primary care and specialty care physicians in the Eastern United States had the lowest total compensation of any region in 2013, the Medical Group Management Association reported. Specialists in the East earned $364,000, and primary care physicians earned $222,000. Compensation for specialists was highest in the South, at $434,000, with primary care physicians there earning $238,611. Primary care physicians in the West earned slightly more, reporting the highest total at $239,968, with specialists earning an average of $401,000. In the Midwest, specialists earned almost $408,000, and primary care physicians averaged $236,000, according to the MGMA. Nonmetropolitan areas reported the lowest compensation rates by population, with primary physicians earning more than $223,000 and specialists earning $337,000 in areas with less than 50,000 residents. The highest-earning areas by population were metro- politan areas of 50,000 to 250,000 people, where primary care physicians earned $241,000 and specialty physicians earned $422,000. Both specialists and nonspecialists in metropolitan areas of more than 1,000,000 people averaged marginally more than physicians in areas of between 250,001 and 1,000,000 people. The MGMA data were collected from almost 4,200 medical groups representing more than 66,000 providers. lfranki@ frontlinemedcom.com contaminated with microbials, drugs, mycotoxins, and heavy metals, the authors noted. “Also, unidentifed interactions with medications used concomitantly may be responsible for toxicity, yet are difcult to establish.” The authors urged an increased understanding and sense of responsibility for the issue. “All stakeholders, including the dietary supplement industry, regulatory agencies, health care providers, and consumers must take note of these fndings if a culture of safety for herbal dietary supplements use is to be established.” Dr. Navarro did not make any fnancial disclosures. Three coauthors disclosed ties with pharmaceutical companies. [email protected] ABIM responds to �grandfathered’ concerns BY ALICIA AULT Frontline Medical News P hysicians who are grandfathered from maintenance of certifcation requirements may soon be listed diferently on the American Board of Internal Medicine website. The ABIM site currently reports publicly whether or not physicians are “Meeting Maintenance of Certifcation Requirements,” and that status means grandfathered physicians do not appear to be meeting MOC requirements on the American Board of Medical Specialties’ Certifcation Matters website. “ �Not meeting MOC requirements’ is, in essence, a scarlet letter meant to pressure grandparents into enrolling in the current fawed MOC system,” Dr. Mack Harrell, president of the American Association of Clinical Endocrinologists, said in a June 30 letter to the ABIM. The Endocrine Society and AACE have asked that no information be publicly reported until the ABIM addresses the MOC concerns of internal medicine specialists. At an August meeting, ABIM agreed that the language “is causing legitimate confusion.” Grandfathered physicians are encouraged but not required to participate in MOC, yet they are still being listed as either meeting or not meeting MOC requirements, according to an Aug. 15 stateCurrent reporting is meant to pressure grandparents into enrolling in the MOC system. DR. HARRELL ment from the board. ABIM is “exploring what changes to the reporting language can be made,” according to the statement. The issue is making sure that “reporting of certifcation status is clear and consistent across the community of specialty boards.” The nature and timing of a change have not yet been decided by the board, ABIM spokesperson Lorie Slass said. “We want to work with ABMS to make sure there is consistency and clarity in web reporting.” Regardless of whether or not a lifetime certifcate holder chooses to enroll in MOC, they will not lose their certifcation. [email protected] On Twitter @aliciaault GIHEP_7.indd 1 4/22/2014 2:20:38 PM NEWS 8 O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S FROM THE AGA JOURNALS Drug combos increase upper GI bleeding risk BY AMY KARON Frontline Medical News C ombining nonsteroidal anti-infammatory drugs with selective serotonin reuptake inhibitors increased the risk of upper gastrointestinal bleeding by up to 190% beyond the baseline risk found for NSAID monotherapy, according to researchers. The report is in the October issue of Gastroenterology. Patients also faced excess risks of upper GI bleeding when they took corticosteroids, aldosterone antagonists, or anticoagulants together with low-dose aspirin or nonselective NSAIDs, although the efect was not seen for COX-2 inhibitors, reported Dr. Gwen Masclee at Erasmus Medical Center in Rotterdam, the Netherlands and her associates. The fndings should help clinicians tailor treat- G astrointestinal toxicity is the major issue limiting nonsteroidal anti-infammatory use. The excess annual risk of upper gastrointestinal bleeding per 1,000 patients is about 1 with lowdose aspirin, about 2 with coxibs, and about 4-6 with traditional NSAIDs (ibuprofen, naproxen). However, the risk of upper gastrointestinal bleeding increases markedly with several factors, including the use of concomitant medications. Ideally, large randomized trials comparing NSAIDs with and without a concomitant medication would inform our assessment of risk. However, few such DR. LAINE trials are available, so we commonly rely on observational database studies, such as that of Masclee et al. These studies have the important beneft of large sample size and “real world” results, but also have potential limitations, including reliability of data (for example, accuracy of diagnostic coding) and potential bias because of unequal distribution of confounding factors between cases and controls. Masclee et al. report signifcant synergy (more than additive risk) of traditional NSAIDs with ments to minimize upper GI bleeding, particularly for elderly patients who often take multiple drugs, the investigators wrote (Gastroenterology 2014 [doi:10.1053/j.gastro.2014.06.007]). The researchers analyzed 114,835 cases of upper gastrointestinal bleeding, including all gastroduodenal ulcers and hemorrhages extracted from seven electronic health record databases from the Netherlands, Italy, and Denmark. Cases served as their own controls, they noted. Monotherapy with prescription nonselective NSAIDs increased the chances of an upper gastrointestinal bleed by 4.3 times, compared with not corticosteroids, SSRIs, aldosterone antagonists, and antithrombotic agents other than low-dose aspirin (although risk was increased with traditional NSAIDs plus low-dose aspirin). Low-dose aspirin was synergistic with antithrombotic agents and corticosteroids, while coxibs were synergistic with low-dose aspirin and SSRIs. The results of Masclee et al. support current North American guidelines, which suggest use of proton pump inhibitors or misoprostol for traditional NSAID users taking concomitant medications such as antithrombotics, corticosteroids, or SSRIs, and use of PPIs for low-dose-aspirin users taking antithrombotics or taking corticosteroids if greater than or equal to 60 years old. Their results also suggest further evaluation of aldosterone antagonists is warranted as another possible risk factor. Dr. Loren Laine, AGAF, is professor of medicine, Yale School of Medicine, New Haven, Conn. He is on Data Safety Monitoring Boards for studies supported by Eisai, BMS, and Bayer; and is a consultant for AstraZeneca. using any of the drugs studied (95% confdence interval, 4.1-4.4). Bleeding risk from taking either nonselective NSAIDs or corticosteroids was the same, the researchers said, adding that studies have yielded inconsistent fndings on the topic. The incidence ratios for monotherapy with lowdose aspirin and COX-2 inhibitors were slightly lower at 3.1 (95% CI, 2.9-3.2) and 2.9 (95% CI, 2.73.2), respectively, they added. Combining nonselective NSAIDs or COX-2 inhibitors with SSRIs led to excess risks of upper gastrointestinal bleeding of 1.6 (95% CI, 0.5-2.6) and 1.9 (95% CI, 0.2-3.4), respectively. “From a biological point of view, this interaction seems plausible because SSRIs decrease the serotonin level, resulting in impaired thrombocyte aggregation and an increased risk of bleeding in general,” they said. Corticosteroids combined with nonselective NSAIDs led to the greatest increases in bleeding risk, with an incidence ratio of 12.8 (95% CI, 11.1-14.7), compared with nonuse of any drug studied, and an excess risk of 5.5 (3.7-7.3), compared with NSAID use alone, said the researchers. Adding aldosterone antagonists to nonselective NSAIDs led to an excess risk of 4.46, compared with using nonselective NSAIDs alone, they reported (95% CI, 1.79-7.13). Because the study did not capture over-the-counter NSAID prescriptions, it could have underestimated use of these drugs, the investigators said. Also, changes in health or NSAID use during the study could have created residual confounding, although sensitivity analyses did not reveal problems, they reported. Misclassifcation of some data could have led them to underestimate risks, the researchers noted. “Finally, we did not take any carryover efect or dose of drug exposure into account, which potentially limits the generalizability concerning causality of the associations,” they concluded. Five authors reported employment or other fnancial support from Erasmus University Medical Center, AstraZeneca, Janssen, PHARMO Institute, and the European Medicines Agency. The other authors reported no relevant fnancial conficts of interests. [email protected] Pediatric IBD rose by more than 40% in 15 years BY AMY KARON Frontline Medical News P ediatric infammatory bowel disease grew by more than 40% in a 15-year period in Ontario, Canada, according to a retrospective cohort study published in the October issue of Gastroenterology. Although rates of infammatory bowel disease (IBD) rose in children and adolescents of all ages, the steepest increase occurred in children with very-early-onset IBD (VEO-IBD), de- fned as disease diagnosed before they were 10 years old, said Dr. Eric Benchimol at the University of Ottawa, and his associates. But these patients also tended to use fewer health services and have fewer surgeries for IBD, compared with older children with the disease, the investigators said (Gastroenterology 2014 October [doi. org/10.1053/j.gastro.2014.06.023]). The fndings add to research indicating that VEO-IBD is a distinct form of IBD and indicate the need to assess subgroups of these patients to look at phenotype, genotype, intestinal microbiome, and treatment response, the investigators said. For the study, researchers created a cohort based on an algorithm of health care visits that identifed all children and adolescents in Ontario diagnosed with IBD before age 18 years. The anal- ysis included 7,143 patients with IBD, among whom about 14% had VEOIBD, the investigators reported. The overall rate of IBD in children up to 18 years old increased from 9.4 to 13.2 cases per 100,000 population from 1994 through 2009 (P less than .0001), the researchers said. And the yearly increase in VEO-IBD averaged 7.4% – more than three times greater than the 2.2% average annual rise among children diagnosed at 10 years and oldContinued on following page NEWS GIHEP NEW S. COM • OCT OBE R 2014 9 FROM THE AGA JOURNALS Continued from previous page er, the investigators reported. But health care utilization trends did not mirror changes in incidence, Dr. Benchimol and associates reported. For example, children diagnosed tis were less likely to undergo colectomy than were older girls (HR, 0.88; 95% CI, 0.47-1.63) and boys (HR, 0.42; 95% CI, 0.21-0.85). In contrast, rates of IBD-related surgery and hospitalization were similar between children diagnosed at 6-9.9 years of age and those diagnosed at age 10 up to 18 years, the investigators said. A cohort study from the United States also found a lower likelihood of surgery in children with VEO-IBD, the researchers noted. Large-bowel involvement without ileal disease is prominent in young children with IBD, and these patients might be unlikely to undergo resection because colectomy requires a permanent ostotomy, they added. [email protected] VITALS Key clinical point: Although the steepest rise in infammatory bowel disease occurred in children diagnosed before age 10 years, children diagnosed before age 6 years had the lowest rates of IBD-related outpatient visits, hospitalizations, and surgeries. Major fnding: Rates of pediatric IBD increased by more than 40% between 1994 and 2009 in Ontario, Canada. Rates rose by an average of 7.4% annually in children diagnosed before age 10 years, compared with 2.2% for children diagnosed from 10 years to before 18 years of age. Rates of outpatient visits, hospitalizations, and IBD-related surgeries were signifcantly lower in children diagnosed before age 6 years, compared with children diagnosed at 10 years or older. Data source: Retrospective study of the Ontario Crohn’s and Colitis Cohort, which included 7,143 children and adolescents with IBD diagnosed between 1994 and 2009 in Ontario, Canada. Disclosures: The work was supported by grants and researcher awards from the American College of Gastroenterology, the Ontario Ministry of Health and Long-Term Care, the Canadian Institutes of Health Research, the Crohn’s and Colitis Foundation of Canada, the National Institutes of Health, the Wolpow Family Chair in IBD Treatment and Research, the Ontario Ministry of Research and Innovation, and the Leona M. and Harry B. Helmsley Charitable Trust. The authors reported no conficts of interest. before they were 6 years old had signifcantly fewer outpatient visits for IBD, compared with children diagnosed at 10 years and older (odds ratio for girls, 0.67; 95% confdence interval, 0.58-0.78; OR for boys, 0.86; 95% CI, 0.75-0.98). Furthermore, patients diagnosed before age 6 years were less likely to be hospitalized for IBD than were older children with the disease (HR for girls, 0.70; 95% CI, 0.56-0.87; HR for boys, 1.12; 95% CI, 0.94-1.33), the investigators said. The likelihood of undergoing intestinal resection also was lower for children diagnosed before age 6 years with Crohn’s disease, compared with older girls (HR, 0.35; 95% CI, 0.16-0.78) and boys (HR, 0.59; 95% CI, 0.34-0.99), said the researchers. And patients diagnosed before age 6 years with ulcerative coli- Leave questions in the past. Get answers as to why response to adalimumab or infliximab may be lost. PROMETHEUS® Anser™ ADA measures both serum adalimumab levels and antibodies to adalimumab. PROMETHEUS® Anser™ IFX measures both serum infliximab levels and antibodies to infliximab. TM PROMETHEUS, the Link Design, For the person in every patient, ANSER, and the ANSER design mark are trademarks or registered trademarks of Société des Produits Nestlé S.A. Vevey, Switzerland. ©2013 Société des Produits Nestlé S.A. Vevey, Switzerland. All rights reserved. ADA13044 08/13 A Nestlé Health Science Company Prometheus diagnostic services provide important information to aid in the diagnosis and management of certain diseases and conditions. How this information is used to guide patient care is the responsibility of the physician. Assays and methods within these tests may be covered by one or more US pending or issued patents. For details, please go to www.prometheuslabs.com. 9410 Carroll Park Drive San Diego, CA 92121 888-423-5227 • 858-824-0896 fax www.prometheuslabs.com 10 NEWS O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S FROM THE AGA JOURNALS Model cut CT scans of Crohn’s patients by 43% BY AMY KARON Frontline Medical News A risk stratifcation model that determined whether patients with Crohn’s disease needed computed tomography cut scans of these patients in emergency departments by 43%, with a miss rate of only 0.8%, according to researchers. The report was published in the October issue of Clinical Gastroenterology and Hepatology. Computed tomography scans yield nonsignificant findings for almost one-third of patients with Crohn’s disease (CD) who present to emergency departments, said Dr. Shail Govani of the University of Michigan in Ann Arbor and his associates. By using their model to identify patients with serious gastrointestinal complications as opposed to straightforward intestinal infammation, emergency departments could prevent more than 250 cancer cases and save more than $80 million per decade in the United States, the investigators added. Patients with CD may be exposed to increasing cumulative radiation levels, and 30% of this exposure occurs in emergency departments, with 75% due to CT scans, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j. cgh.2014.02.036]). For the study, the investigators retrospectively reviewed electronic By using the model to identify patients with serious gastrointestinal complications, emergency departments could prevent more than 250 cancer cases and save more than $80 million per decade in the United States. medical records from the University of Michigan from 2000 through 2011, identifying 613 adults with CD who made 1,095 visits that included CT scans within 24 hours of presentation. The researchers then modeled associations between laboratory values and perforation, abscess, or other serious complications as opposed to intestinal infammation. Patients averaged 1.8 CT scans during the decade-long study period, and the overall rate of CT scans during that time rose from 63% to 87%, the investigators said. Only 16.8% of scans revealed a complication that would change clinical management, they reported. Only C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were signifcantly associated with complications (odds ratio for CRP, 1.10; 95% confdence interval, 1.05-1.15; P less than .001; odds ratio for ESR, 1.02; 95% CI, 1.01-1.03; P less than .001), the researchers said. Adding ESR to 5 x CRP and not Continued on following page NEWS GIHEP NEW S. COM • OCT OBE R 2014 11 FROM THE AGA JOURNALS Continued from previous page scanning patients with a resulting value of 10 or less would avoid CT scans in 18.5% of patients, they reported. But with use of the more complex logistic regression model instead of the simpler equation, scans could be avoided for 43.0% of patients, with a miss rate of 0.8%, they said. Based on the study, patients assessed as likely to have complications should undergo a standard CT scan of the abdomen and pelvis with nonbarium contrast to avoid barium peritonitis, said Dr. Govani and associates. Other patients should forego CT scans, have a consult with a gastroenterologist prior to further imaging, or undergo lower-radiation CT enterography, depending on presenting signs and probability of infammation, they added. The researchers said they were unable to construct good models that included obstruction as an outcome. Patients with suspected obstructions should have abdominal x-rays and then CT if an obstruction remained likely, they said. “These models are limited in that they are retrospective and represent data from one center,” the investigators added. “Although our internal validation with 10-fold cross-validation shows that these models have good performance characteristics, further external validation studies are needed to determine whether these models are generalizable to CD patients elsewhere.” The authors are prospectively testing the algorithms and hope to continue to validate and study them in emergency departments, they said. The Infammatory Bowel Disease Working Group, the Department of Veterans Afairs, and UCB supported the research. The authors reported having no conficts of interest. [email protected] MicroRNA test improved preop pancreatic cancer diagnosis BY AMY KARON Frontline Medical News C ytology and a microRNA-based test identifed pancreatic cancer 91% of the time in specimens obtained by endoscopic ultrasound-guided fne-needle aspiration – a substantial improvement, compared with cytology alone, researchers reported in the October issue of Clinical Gastroenterology and Hepatology. The microRNA-based test could help reduce repeated fne-needle aspirations (FNAs) due to indeterminate cytologies, said Dr. Randall Brand, AGAF, of the University of Pittsburgh Medical Center and his associates. Correctly assessing pancreatic cancer before surgery also could help patients start neoadjuvant therapy sooner if appropriate, they noted. Several microRNAs are expressed abnormally in patients with pancreatic ductal adenocarcinoma. T The new test contains fve of these sequences and is the frst of its type for pancreatic cancer, the researchers said. To evaluate the assay, they assessed and compared relative quantitative polymerase chain reaction and cytology results from 95 formalin-fxed parafn-embedded specimens and 228 endoscopic ultrasound-guided FNAs. Specimens were collected during routine visits by patients with solid pancreatic masses, the investigators said (Clin. Gastroenterol. Hepatol. 2014 Oct. [doi: 10.1016/j.cgh.2014.02.038]). The test, used with cytology, correctly identifed pancreatic cancer in 91% of positive specimens (95% confdence interval, 85.6%-94.5%), while cytology alone had a sensitivity of 79% (95% CI, 72.2%-84.5%), the researchers reported. Cytology and the microRNA test each had positive predictive values greater than 99% (95% CI, 96%-100%), they added. When used alone, the microRNA test had a di- he diagnosis of pancreas cancer is based on Brand et al. have presented the results of a the results of clinical presentation, cross-seclarge multicenter 3-year validation trial designed tional imaging, and endoscopic ultrasound to determine the performance characteristics of (EUS)–guided fne-needle aspiration. A defnitive a 5-microRNA-based classifer for the diagnosis tissue diagnosis is often required beof pancreas cancer on 228 EUS-FNA fore chemotherapy, radiation therapy, specimens. In the study, the false-negand surgery. Because of the greater ative rate for pancreas mass FNA was sensitivity of EUS over CT scanning, 20%. The results of the miRNA testing EUS-guided FNA is often the procerevealed a sensitivity of 83% and a dure of choice. EUS-guided FNA is false-negative rate of 17%. However, highly dependent on the identifcation when both the cytology and the miof malignant cells in the FNA specicroRNA test were used in conjunction, mens. The presence of a dense perithe sensitivity increased to 91% with a tumoral stroma containing fbroblasts specifcity of 96%. often interferes with the aspiration and DR. BRUGGE The use of molecular markers in identifcation of malignant cells. the management of FNA cytology The cytological criteria for the diagnosis of specimens provides an opportunity to objectify pancreas adenocarcinoma with FNA requires the the fndings of aspirated tissue analysis. With an presence of a number of cellular features such as objective test, the interpretation of specimens is dark chromatin, large nuclei, and aggregates of not dependent upon the subjective fndings of a atypical cells. Not surprisingly, cytologists adhere cytologist. It seems likely that this type of testrigidly to the criteria for the diagnosis of adenoing will gradually improve FNA cytology. carcinoma resulting in a highly specifc test with moderately high sensitivity. The sensitivity of EUS Dr. William R. Bruge, AGAF, is director, Pancreas FNA for the diagnosis of pancreas cancer remains Biliary Center, Massachusetts General Hospital, Bosstubbornly imperfect, between 85% and 95%. ton. He reported no conficts of interest. agnostic sensitivity of more than 82% and a specifcity of 96% – better than cytology on the same specimens, the investigators said. The test correctly found pancreatic cancer in 22 of 39 specimens previously assessed as benign, indeterminate, or nondiagnostic by cytology, they said. The researchers separately assessed 46 specimens collected percutaneously instead of by EUS-guided FNA and found much lower (58%) diagnostic MicroRNA sequences can be reliably recovered from both formalin-fxed and FNA specimens, making them a �particularly promising’ class of biomarkers for pancreatic and other cancers. sensitivity and a higher rate of technical failures, although specifcity and predictive value still approached 90%, said the investigators. The percutaneous specimens all were collected from two study sites outside the United States, so further studies would need to validate whether a percutaneous approach could replace EUS-guided FNA, they said. Cytology and microRNA testing also had to be performed on diferent FNA specimens, a limitation that “could have contributed to some of the observed discrepancies between cytology and molecular results,” the investigators said. Pancreatic cancer remains notoriously difcult to treat, with overall 5-year survival rates of only about 6%. MicroRNA sequences are stable and can be reliably recovered from both formalin-fxed and FNA specimens, making them a “particularly promising” class of biomarkers for pancreatic and other cancers, the researchers said. Based on the study results, future studies should explore the test’s prognostic potential, such as for distinguishing patients with resectable tumors that are likely to progress. The study was supported by Asuragen and a grant from the German Federal Ministry of Education and Research. Dr. Brand and another author reported that they are on the clinical advisory board of Asuragen, and 6 of 27 coauthors reported being employees of the company. The rest reported no fnancial conficts of interest. [email protected]      NEWS FROM THE AGA GIHEP NEW S. COM • OCT OBE R 2014 Impact of the AGA Research Foundation Quick Quiz Q1: Hereditary pancreatitis is NOT: A. Associated with an increased risk of developing pancreatic cancer. B. Caused by mutations in cationic trypsinogen. C. Associated with 100% penetrance. D. An autosomal dominant trait. Q2: You are seeing a 20-year-old woman with a history of ulcerative colitis diagnosed at the age of 12. At that time, she presented with ulcerative proctitis that was well controlled with mesalamine suppositories. Twelve months ago she developed worsening symptoms that included bloody diarrhea; colonoscopy revealed moderate to severe pancolitis. She was started on Asacol® (mesalamine) 800 mg three times a day and prednisone. She has been unable to wean of the steroids without experiencing recurrent symptoms. Six months ago she was started on azathioprine at 2.5 mg/kg without signifcant response. She is currently on prednisone 30 mg daily and has 4-5 soft bowel movements per day. What would you recommend next? A. Change the Asacol® to Colazal® (balsalazide) and follow clinically for the next 4 weeks. B. Continue azathioprine and start infiximab 5 mg/kg IV at 0, 2, and 6 weeks. C. Taper of the prednisone and start Entocort EC (budesonide) 9 mg daily. D. Stop the azathioprine and start methotrexate at 15 mg IM per week. E. Continue azathioprine and start tacrolimus at 0.1 mg/kg per day divided twice daily. Quick Quiz Answers QI: ANSWER: C Critique Hereditary pancreatitis is a distinct clinical entity inherited as an autosomal dominant trait with incomplete penetrance and caused by mutations in cationic trypsinogen (PRSS1). This process is associated with up to a 60-fold increased risk of pancreatic cancer. References 1. Greer J.B., Whitcomb D.C. Infammation and pancreatic cancer: an evidence-based review. Curr. Opin. Pharmacol. 2009;9:411-8. 2. Teich N., Rosendahl J., Tóth M., et al. Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis. Hum. Mutat. 2006;27:721-30. 3. Whitcomb D.C., Gorry M.C., Preston R.A., et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat. Genet. 1996;14:141-5. Q2: ANSWER: B Critique This patient has steroid-dependent ulcerative colitis. She has not responded to Asacol® at 2.4 g daily and azathioprine. Even though azathioprine has a slow onset of action, therapeutic efcacy should be expected within 3-6 months of initiation of treatment. This patient should be started on a biologic agent such as infiximab. If she does not respond to treatment with infiximab, she should be considered for colectomy with ileal pouch– anal anastomosis. Changing the Asacol® to a mesalamine formulation with a diferent 15 release mechanism – such as balsalazide – would not likely change this patient’s disease course but would delay further therapeutic interventions. Entocort EC (budesonide) is a glucocorticosteroid with a controlled ileal release formulation; it undergoes signifcant frst-pass metabolism in the liver, which reduces its systemic toxicity compared to prednisone. It is given to patients with mild to moderate ileal or ileocecal Crohn’s disease. However, a new formulation of budesonide in an MMX release system has recently been shown to be superior to placebo in ulcerative colitis, more particularly for left sided colitis. Nonetheless, the study population did not include prednisone-resistant or -dependent patients, and so this strategy of tapering from prednisone to budesonide in this patient will be incorrect regardless. Methotrexate is effective in inducing remission in patients with Crohn’s disease and its efcacy in UC has not been established. Tacrolimus is an oral calcineurin-inhibitor that is used in transplant patients. Its role in infammatory bowel disease has not been established. References 1. Rutgeerts P., Sandborn W.J., Feagan B.G., et al. Infiximab for induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 2005;353:2462-76. 2. Sandborn W.J. A review of immune modifer therapy for infammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am. J. Gastroenterol. 1996;91:423-33. [email protected] T he AGA Research prevention, treatment, Foundation, the and cure of digestive charitable arm of the diseases has been made American Gastroin the research enterological Aslaboratory of a sociation (AGA), talented young plays an importinvestigator. ant role in medi“This award cal research. provided me The foundation the support to provides grants to examine aspects young scientists of colonic stem at a critical time cell homeostaDR. POWELL in their careers. sis and tumor The mission of initiation using the AGA Research Founsuper resolution microsdation is to raise funds to copy, perhaps affording a provide support to young physical visualization of researchers in the felds of colonic cellular processes, gastroenterology and hepa- which has not been previtology. ously possible,” said Anne The research program E. Powell, Ph.D. of the AGA has had an imDr. Powell is a Vanderportant impact on digestive bilt University 2014 AGA disease research for the last Research Scholar Award 30 years in the following Recipient. ways: “My long-term aim is to ▶ More than $43 million be an independent inveshas been provided in retigator and a leader in the search grants. feld of colonic stem cell ▶ More than 780 scientists biology and this award is have been awarded rea critical step toward that search grants. goal,” said Dr. Powell. ▶ Ninety percent of inves“Undoubtedly, without tigators who received the generous support from an AGA Research Schol- this research scholar award ar Award (RSA) over from the AGA Research the past 10 years have Foundation, this work continued to conduct would not be possible,” she research in the fields of said. gastroenterology and At a time when funding hepatology. from the NIH and other ▶ More than 85% of RSA traditional sources of suprecipients in the past 10 port is in decline, the AGA years received funding Research Foundation is from the National committed and ready to Institutes of Health support young investigasubsequent to their RSAs; tors. The funding provided more than 50% of these by the foundation helps to researchers received $1 launch discoveries that will million or more in NIH continue to improve GI grant support. practice and better patient AGA grants have led to care. various discoveries. These The AGA Research include new approaches Foundation provides a to the downregulation of key source of funding at a intestinal infammation, a critical juncture in a young test for genetic predisposiresearcher’s career. By jointion to colon cancer, and ing others in donating to autoimmune liver disease the AGA Research Foundatreatments. tion, you will ensure that The importance of researchers have opporthese awards is made clear tunities to continue their by the fact that virtually life-saving work. every major advance [email protected] ing to the understanding, GIHEP_20.indd 1 7/28/2014 10:26:17 AM GI ONCOLOGY GIHEP NEW S. COM • OCT OBE R 2014 Screening has risks Unnecessary from page 1 patient died of other causes. In one of the studies, researchers analyzed data from the population-based National Health Interview Survey, which assesses approximately 90,000 Americans each year to provide health information representative of the U.S. population. They focused on 27,404 participants aged 65 years and older who reported on the cancer screening they underwent between 2000 and 2010. A validated mortality index was used to calculate each respondent’s 9-year mortality risk based on factors such as age, sex, smoking status, body mass index, comorbidities, hospitalizations, and functional measures, said Dr. Trevor J. Royce of the departments of radiation oncology and medicine, University of North Carolina at Chapel Hill, and his associates. They found that contrary to numerous recommendations, “a sizable proportion of the U.S. population who have less than a 9-year life expectancy” underwent screening for cancer, including 55% of men who were screened for prostate cancer, 41% of people screened for colorectal cancer, 38% of women screened for breast cancer, and 31% of women screened for cervical cancer, Dr. Royce and his associates said ( JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/jamainternmed.2014.3895]). Cancer screening was also common in people whose life expectancy was less than 5 years, or even less than 3 years. Even though the lack of net beneft from cancer screening in such patients “is widely recognized and publicized in clinical practice guidelines, important obstacles exist to reliably applying these guidelines.” Chief among these obstacles is the lack of a simple, reliable tool for assessing life expectancy in clinical practice. In addition, physicians may fnd it difcult to communicate to patients that they are very likely to die within the next few years, and patients may fnd it difcult to accept that they have a limited life expectancy. Physicians’ fear of litigation further contributes to overscreening, Dr. Royce and his associates said. In the other study, researchers used microsimulation modeling to assess whether screening more intensively than recommended for colorectal cancer would be favorable for individual patients or for society as a whole. They created two hypothetical cohorts of 10 million Medicare benefciaries at average risk for the disease: The frst contained patients who had a negative screening colonoscopy at age 55, and the second contained patients who had never been screened for colorectal cancer, said Dr. Frank van Hees of the department of public health, Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates. The model simulated recommended screening (that is, colonoscopy at ages 65 and 75 years), as well as several shorter screening intervals, screening up to age 85 years, and screening up to age 95 years. It factored into the analyses the sensitivity rates for colonoscopy for adenomas or carcinomas at various stages, age-specifc risks for GI and cardiovascular complications requiring hospitalization, and survival rates after a variety of possible clinical diagnoses. “For each scenario of more intensive screening than recommended, we determined the associated increase in colorectal cancer cases prevented, colorectal cancer deaths prevented, life-years gained, life-years with cancer care prevented, colonoscopies performed, and complications 21 experienced,” the investigators said. The balance among benefts, burden, and harm was unfavorable in almost every scenario tested, outside the recommended screening scenario. Similarly, when colonoscopy was continued to age 85 years instead of ceasing at age 75 years, “the overall loss of quality of life exceeded the associated increase in life-years gained.” Harms were even greater when the screening interval was reduced to 3 years. “This study provides strong evidence and a clear rationale for clinicians and policy makers to actively discourage this practice,” Dr. van Hees and his associates said ( JAMA Intern. Med. 2014 Aug. 18 [doi:10.1001/ jamainternmed.2014.3889]). [email protected] PERSPECTIVE Discuss life expectancy for a change T o reduce unneeded cancer screening, clinicians must alter their approach to discussions with older patients. Life expectancy should be addressed, because there is substantial heterogeneity among older persons in life expectancy and comorbidity burden. Informational tools should be developed that can help patients weigh anticipated benefts and harms of screening, given their individual risk. It will truly be a new era when providers will be evaluat- ed, in part, by their ability to refrain from ordering cancer screening tests for some of their patients. Dr. Cary P. Gross is at the Cancer Outcomes, Public Policy, and Efectiveness Research Center at Yale University, New Haven, Conn. He reported having ties to FAIR Health, Medtronic, Johnson & Johnson, and 21st Century Oncology. These remarks were taken from his invited commentary accompanying the two reports on cancer screening (JAMA Intern. Med. 2014 Aug. 18). Adjuvant S-1 an option for stage III colon cancer BY SHARON WORCESTER Frontline Medical News T he oral fuoropyrimidine S-1 is efective as adjuvant chemotherapy for stage III colon cancer, according to fndings from the randomized, open-label, phase III noninferiority trial in Japan. Disease-free survival was 75.5% at 3 years in 758 patients with curatively resected stage III colon cancer who were randomized to receive S-1, compared with 72.5% in 760 such patients who received tegafur-uracil plus leucovorin (stratifed hazard ratio for disease-free survival, 0.85), Dr. M. Yoshida of Osaka Medical College Hospital, Osaka, Japan, and colleagues reported online in Annals of Oncology. The fndings were reported on behalf of the Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) study group. The stratifed HR for disease-free survival was similar even after excluding 14 patients who did not receive the allocated treatment, and after adjusting for key baseline factors (Ann. Oncol. 2014 Aug. 14 [doi:10.1003/annonc/mdu232]). The fndings demonstrate the efcacy of S-1 by confrming its noninferiority to tegafur-uracil plus leucovorin (UFT/LV), the investigators said. Postoperative adjuvant chemotherapy for patients with stage III colon cancer is the standard of care internationally, and Western guidelines call for frst-line treatment with intravenous 5-fuorouracil (5-FU) and LV or capecitabine combined with oxaliplatin (the FOLFOX or CapeOX regimens). Fluoropyrimidine monotherapy is also a treatment option. S-1, which combines tegafur, gimeracil, and oteracil, has been shown in phase III studies to be noninferior to conventional 5-FU–based regimens when used in combination with other cytotoxic agents for the treatment of advanced gastric cancer and advanced colorectal cancer. As adjuvant chemotherapy, postoperative S-1 treatment signifcantly improved survival in patients with gastric cancer and pancreatic cancer, but its efcacy for colon cancer had not been established, they noted. Patients included in the current study were aged 20-80 years (median, 66 years), and 35.3% were aged 70 or older. Those assigned to the S-1 group received 80-120 mg daily (depending on body surface area) on days 1-28, every 42 days for four courses; those assigned to the UFT/LV group received 300-600 mg of UFT daily (depending on body surface area) and 75 mg of LV daily on days 1-28, every 35 days for fve courses. No signifcant diferences were noted between the S-1 and UFT/LV groups with respect to safety and feasibility. The fndings suggest that S-1 could be a new treatment option – with multiple potential advantages over UFT/LV – for adjuvant chemotherapy in patients with colon cancer, the investigators said. Among the advantages are lower cost (in Japan, the cost is half that of UFT/LV), dosing convenience, and dramatically reduced risk of hand-foot syndrome, compared with capecitabine (1.3% vs. 60%), they said. This study was supported by the Foundation for Biomedical Research and Innovation, Translational Research Informatics Center, under a funding contract with Taiho Pharmaceutical, Japan. Dr. Yoshida reported receiving honoraria and/or research funding from Taiho Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, Merck Serono, Bayer Yakuhin, Daiichi Sankyo, Sanof, Kyowa Hakko Kirin, Nippon Kayaku, Ono Pharmaceutical, and Jansen Pharmaceutical. [email protected] 22 IBD AND INTESTINAL DISORDERS Encapsulated fecal transplant Pill from page 1 work by restoring the gut fora to a normal balance after having been disrupted by antibiotic treatment. It is not the frst attempt to encapsulate a fecal transplant; Dr. Thomas Louie of the University of Calgary (Alberta), presented data on his very effective formulation against C. difcile at the ID Week annual meeting in 2013. In the current study, the frst cohort received a mean dose of 1.5 × 109 spores and the second cohort received a dose of 1 × 108 spores. The aim is to contain the dose in a few tablets for a commercial product, Dr. Cook said. All doses were given on 1 or 2 days at the study’s start. Patients ranged between 22 and 88 years of age, and all had three or more laboratory-confrmed C. difcile infections over the previous year. They had to have a life expectancy of at least 3 months and be able to give informed consent. They were excluded if they had any immunosuppression, a history of irritable bowel disease, total colectomy, cirrhosis, a need for antibiotics within 6 weeks of baseline, prior fecal transplant, or if they were in intensive care. There were 10 women and fve men in each cohort. After patients stopped taking antibiotics, there was a washout period after which they took SER-109. Stool was collected on day 4 and at 1, 2, 4, 8, and 24 weeks. Efcacy was assessed at the 8-week time point. In the frst group, 13 of the 15 patients achieved the protocol-defned endpoint: absence of C. difcile over the 8 weeks. The two patients who failed had self-limited, transient diarrhea with a positive C. difcile test, but neither required antibiotics and both recovered within 24 hours, so they were considered to not have recurrent C. difcile, said Dr. Cook. In the second cohort, 14 of the 15 patients were free of C. difcile at 8 weeks. The patient who failed had diarrhea and a positive C. difcile test, and the diarrhea did not resolve on its own. She required antibiotics to achieve remission. The company hopes to eventually conduct a phase III study and seek Food and Drug Administration approval, but it is too early to say when that might occur, said Dr. Cook. [email protected] PERSPECTIVE Innovations in microbiome research A GA hosted the annual James W. Freston conference in Chicago this August, and the topic was therapeutic innovations in microbiome research and technology, with a focus on fecal microbiota transplantation (FMT). There were over 140 participants from 16 countries present. The 2-day meeting opened with lectures highlighting evolving knowledge about the human microbiome. These were followed by additional presentations about FMT as a treatment for Clostridium difcile, infammatory bowel disease, and intriguing work on the role of the gut microbiome in the metabolic syndrome. Some of the FMT presentations are summarized in this issue of GI & Hepatology News. The fnal session of the meeting concerned institutional review board regulation of trials involving FMT, and updates from the Food and Drug Administration. It is clear that FMT is an efective treatment for recurrent C. dif. The short-term safety of FMT in existing trials is reassuring, but there was consensus at the meeting that we need further study of long-term outcomes of recipients. Studies of FMT for IBD, irritable bowel syndrome, and other conditions are quite limited at this time, and it is clear that more research is needed before we will understand the associations and potential causality related to the microbiome. Studies of what additional viruses, phages, and proteins may be transferred from a donor to recipient are desperately needed. The evidence for safety and efcacy for any conditions beyond C. dif is lacking. Many attendees emphasized the need for better education about the potential risks. Dr. David T. Rubin is Joseph B. Kirsner Professor of Medicine, section chief of gastroenterology, hepatology, and nutrition, and co-director of the Digestive Diseases Center, University of Chicago. O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S Early data on FMT for severe C. diffcile and IBS matter of weeks.” The study followed 13 patients for Frontline Medical News an average of 11 months. All had irritable bowel syndrome (IBS) that was ecal microbiota transplantation refractory to diet, probiotic, antibiotsuccessfully treated severe and/or ic, and/or antidepressant therapy. complicated ClostridThe main outcome was ium difcile infection in a assessed by a 41-item quesretrospective, multicenter, tionnaire that evaluated long-term follow-up study severity of abdominal pain, of 17 patients in whom bloating, fatus, diarrhea, conventional therapy had constipation, and overall failed. Patients had a mean quality of life. age of 66 years (ranging Most of the patients from 38 to 89 years), and (7/13) were women. 13 of them were women. The diagnoses were diDR. ARONIADIS The 14 inpatients and 3 arrhea-predominant IBS outpatients were treated for (nine), constipation-preeither severe or complicated C. difcile dominant IBS (three), and mixed IBS infection. They were followed for a (one). mean of 11 months (ranging from 1 to The donor pool comprised pa42 months) after FMT. tients’ relatives, spouses, or close Diarrhea resolved in 12 patients friends. The transfusion was delivover an average of 6 days after FMT ered once by upper endoscopy. and improved in 4 patients. In 11 There has been speculation about patients with abdominal pain before whether a family member, household transplantation, the pain resolved in member, or someone else is the ideal 8 patients over a mean of 10 days and donor for fecal transplant; however, improved in 3 patients, Dr. Olga C. this study wasn’t powered to address Aroniadis and her associates reported. this, Dr. Aroniadis said. Fifteen of 17 patients had no recurPicking the optimal donor probarence of C. difcile infection within 90 bly depends on accurately detailing days of transplantation, for a primary the microbiome of both donor and cure rate of 88%. One of the two recipient. “In the future, we hope patients with a recurrence within 90 to develop an individual approach days was treated successfully with to FMT, but to do this, we need to a second FMT, for a secondary cure know which specifc bacterial popularate of 94%, said Dr. Aroniadis of tions need to be restored in each paMontefore Medical Center, New tient, and that is several years away.” York, at the 2014 James W. Freston Patients responded to FMT regardconference sponsored by the Ameriless of IBS subtype; however, the numcan Gastroenterological Association. bers of patients in each group were too Many of the inpatients were hospi- few to perform a statistical comparison. talized in the ICU and on vasopressor Dr. Aroniadis and her colleagues support, she said. are planning a randomized controlled “It’s truly a rewarding experience trial that will enroll only patients to watch these severely ill patients with diarrhea-predominant IBS. “We improve after fecal transplantation,” will have a much better sense of the Dr. Aroniadis said. “Fecal transplanta- efcacy of FMT for the treatment of tion even obviated the need for colec- diarrhea-predominant IBS after we tomy in one of our patients.” conduct our clinical trial.” Participants Fecal microbiota transplant imenrolled in the trial will undergo miproved or alleviated symptoms in 9 crobiome analyses before and after of 13 of patients with refractory irri- fecal transplant, which she hopes will table bowel syndrome, a small retroshed some light on how alteration of spective study also determined. the intestinal microbiota correlates A single transfusion of fresh donor with symptoms. feces improved abdominal pain, bowel The present study is the frst to track habits, dyspepsia, bloating, and fatfecal transplant response exclusively in ulence, Dr. Aroniadis reported at the IBS patients, Dr. Aroniadis said. meeting. Dr. Aroniadis had no fnancial disFor some patients, noticeable imclosures. provement occurred within days, Dr. [email protected] Aroniadis said in an interview. “For On Twitter @sherryboschert others it took longer, but in those [email protected] who felt better, they did so within a BY SHERRY BOSCHERT AND MICHELE G. SULLIVAN F IBD AND INTESTINAL DISORDERS GIHEP NEW S. COM • OCT OBE R 2014 23 It’s tough to fnd a good fecal donor BY ALICIA AULT Frontline Medical News F inding healthy stool donors for fecal transplant may be a tough prospect. That’s what Australian researchers have discovered in the course of the FOCUS trial, which aims to determine whether fecal microbiota VITALS Key clinical point: Finding fecal transplant donors is not as simple as once thought. Major fnding: Only 10% of people recruited to be donors for a fecal microbiota transplant study were healthy enough to be eligible. Data source: Donors recruited for the FOCUS study. Disclosures: The study is sponsored by the University of New South Wales, Sydney. The investigators reported no relevant fnancial conficts. transplantation (FMT) is safe and effcacious in the treatment of chronic active ulcerative colitis and in the induction of remission. Dr. Sudarshan Paramsothy and his colleagues at the University of New After several rounds of screening, there were only 12 healthy donors, 10% of the starting 116. DR. PARAMSOTHY South Wales, Sydney, and the University of Melbourne, reported fndings from donor recruitment for the FOCUS (Faecal Microbiota Transplantation in Ulcerative Colitis) trial at the American Gastroenterological Association’s 2014 James W. Freston Conference in Chicago. The FOCUS study began enrolling patients in November, and is continuing to enroll, said Dr. Paramsothy. He and his colleagues also are continuing to recruit fecal donors. The data presented in Chicago were on an initial recruitment efort. Overall, after screening, only 10% of recruits were considered eligible donors. The researchers recruited donors through letters, newspaper ads, and online solicitations. They were told that they would be reimbursed for their time and for the transportation of their stool do- nations to the study site. After responding, recruits were told that they would be expected to make stool donations fve times a week for a minimum of 6 weeks. The researchers had 116 potential donors over a 7-month recruitment period. Forty-seven declined immediately because of the 5-day-a-week donation requirement. Twenty-seven had other issues, including medical comorbidities (13), risk factors for variant Cruetzfeldt-Jakob disease (6), and recent antibiotic use (1), which disqualifed them from the study. Thirty-eight potentially healthy Continued on following page 24 IBD AND INTESTINAL DISORDERS Continued from previous page donors underwent stool and blood testing; 15 of those donors were found to have a variety of parasites or indications of active infection that excluded them from donation: 5 had Dientamoeba fragilis, 5 had Blastocystis hominis, 1 had B. hominis and D. fragilis, 1 had Giardia intestinalis and D. fragilis, 1 had norovirus and Clostridium difcile toxin, and 2 had leukocytes or erythrocytes on stool microscopy. One donor had indeterminate hepatitis C serology. While it is not uncommon for people to have asymptomatic parasite carriage in the gastrointestinal O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S tract, “we did not expect it in such a high proportion,” said Dr. Paramsothy. “Our screened donor population was not an at-risk group,” he said, adding that they were otherwise healthy and had no risk factors or gastrointestinal symptoms. “Our detection rates may have been slightly higher as donor stool WE’RE CHANGING THE NORM FOR PATIENTS WITH CROHN’S DISEASE After Crohn’s surgery, it is common for the disease to return within a few months despite anti-infammatory medicine. At UPMC, our multidisciplinary team developed a new post-op treatment approach that has reduced the recurrence of Crohn’s disease by nearly three fourths. And now many other hospitals are adopting this novel approach. Because when you make patients feel better, it’s normal to want them to stay that way. Learn more at UPMCPhysicianResources.com/Crohns. UPMC is affliated with the University of Pittsburgh School of Medicine. samples were sent to a pathology center with expert, specialized GI parasitologists for review,” Dr. Paramsothy said. There’s also some question as to whether some parasites, such as Blastocystis and Dientamoeba, “are truly pathogenic or rather commensal organisms,” he said, adding that it was thought better to exclude patients with these parasites if there were any doubt. That left 22 potential donors. Further questioning found that two had used antibiotics in between recruitment and stool testing, and one was living with a household member The donor results �suggest that, while FMT is an exciting new therapy, it is diffcult to identify appropriate and willing anonymous donors,’ Dr. Paramsothy said. But that should not have an overall impact on FMT as a therapy. who was positive for D. fragilis. Of the 19 remaining, 1 dropped out and 18 were screened again. Three were excluded because of a body mass index over 30 kg/m2, 1 because of illicit drug use, 1 because of irregular bowel movements after starting a new medication, and 1 because of uncontrolled anxiety and depression. Dr. Paramsothy said that highBMI donors were excluded because some studies have shown that gut microbiota potentially infuence insulin sensitivity and obesity. Illicit drug use is a red fag because it is potentially associated with blood-borne disease acquisition, he said. At the end, there were only 12 healthy donors, 10% of the starting 116. Dr. Paramsothy said that it was not necessary to have a single donor for every single patient in the trial. He said he could not disclose currently the number needed for the study, however. The donor results “suggest that, while FMT is an exciting new therapy, it is difcult to identify appropriate and willing anonymous donors,” Dr. Paramsothy said. But that should not have an overall impact on FMT as a therapy, he said – rather, it might just make it harder for a small practice to establish an in-house FMT program. Dr. Paramsothy reported no relevant fnancial conficts of interest. [email protected] On Twitter @aliciaault LIVER DISEASES GIHEP NEW S. COM • OCT OBE R 2014 25 Diabetes develops from liver grafts donated after DCD BY SUSAN LONDON Frontline Medical News SAN FRANCISCO – The type of liver graft used in transplantation plays a large role in early development of new-onset diabetes, according to a retrospective study of 430 patients from the United Kingdom. A team led by Dr. Hermien Hartog, an honorary clinical fellow in the Liver Unit, Queen Elizabeth Hospital, Birmingham, England, studied patients undergoing primary liver transplant between 2008 and 2012. Patients were excluded from the study if they had preexisting diabetes, had died, or had undergone retransplantation within 90 days. The investigators assessed both the development of new-onset diabetes after transplant (NODAT), using criteria adapted from a published article �Our study confrms known associations with NODAT after liver transplantation but identifes DCD graft as a novel risk factor. ... We hypothesize that hyperglycemia may be related to liver graft function through ischemia-reperfusion– induced hepatic insulin resistance.’ (Transplantation 2013;96:58-64), and its resolution, defned as the date of cessation of antihyperglycemic therapy or the last episode of hyperglycemia. Seventy-nine percent of the patients received grafts donated after brain death (DBD), Dr. Hartog reported at the annual meeting of the 2014 World Transplant Congress. Among the recipients of grafts donated after circulatory death (DCD), the mean warm ischemic time was 21 minutes. With a median follow-up of 2.5 years, the cumulative 1-year incidence of NODAT was 19% in the entire cohort, with a median time to onset of 30 days. In the 44% of afected patients whose NODAT resolved, the median time to resolution help inform new approaches was 150 days post transplanVITALS for graft optimization and setation, Dr. Hartog reported at Key clinical point: Recipients of liver lection. the congress, which was spongrafts donated after circulatory death Session cochair Darius Mirsored by the American Society are at a slightly higher risk for postza, also of the University of of Transplant Surgeons. transplant new-onset diabetes. Birmingham, asked, “Why The cumulative 1-year inMajor fnding: The risk of new-onset does the pattern of recovery cidence of NODAT was 23% diabetes within 90 days of transseem to be diferent in the in DCD graft recipients and plantation was 1.8-fold higher for DCDs versus the DBDs? Also, 18% in DBD graft recipients, a patients who received a DCD graft why are the cumulative incinonsignifcant diference. But than for peers who received a DBD dence and the time frame so when patients were stratifed graft. diferent?” by graft type, “we saw an earData source: A retrospective cohort “Actually, in the literature, ly occurrence and high peak study of 430 primary liver transplant recipients. I have not seen any reports incidence of NODAT in DCD looking at the early postgraft recipients. Also, a larger Disclosures: Dr. Hartog disclosed no relevant conficts of interest. transplant period. So most proportion of these patients reports look at one time point, resolved their NODAT over normally 1 year,” Dr. Hartog time,” she commented. The overall temporal pattern suggested that “the replied. “What I think is that there is an early peak efect that we see of graft type seems to be temporary and [lessens] over time when multifactorial caused by DCD grafts that would explain why there is an early peak, but also why those patients factors come into play,” according to Dr. Hartog. recover later on. I think this peak is a bit obscure In multivariate analyses, the risk of NODAT because there are also other factors that come into within 90 days of transplantation was higher for play, maybe after a while, that will obscure that patients who received a DCD graft (hazard ratio, frst peak. If you would take those other factors 1.8). More detailed analysis showed that the elevaout of the equation, I think you would just see a tion of risk was greatest within the frst 15 days. peak in the early period.” “Our study confrms known associations with Dr. Mirza also wondered about the role of using NODAT after liver transplantation but identifes DCD grafts that are accepted under extended criteDCD graft as a novel risk factor. This causes a temporary efect in the early posttransplant period ria. “So you start of using mainly young, ft DCD livers. Now, the vast majority are extended-criteria that is independent from known risk factors,” Dr. DCD livers. Do you think that plays a role, or is it Hartog commented. “Based on our observations, we hypothesize that too early to say?” “Yes, I think so,” Dr. Hartog said, while adding hyperglycemia may be related to liver graft function through ischemia-reperfusion–induced hepatic that this phenomenon is likely not restricted to DCD grafts. insulin resistance,” she added. “From earlier literature, there is a clear difer“We are currently trying to confrm our data in ence between a living donated graft and deceased an independent data set, which will also include postreperfusion glucose levels and correlation with donation. And it might also be that the extended grafts or the more steatotic grafts may exhibit this the insulin receptor pathway in time-zero liver biefect more than the better grafts.” opsies.” “The clinical relevance of our fndings is as yet [email protected] unknown,” she acknowledged. However, they may Statins linked to lower hepatocellular carcinoma risk BY BIANCA NOGRADY Frontline Medical News U se of statins for any duration of time is associated with a significant reduction in the risk of hepatocellular carcinoma in a low-risk population, according to researchers. In a nested case-control study, re- searchers matched 94 cases of hepatocellular carcinoma to 468 controls by using pharmacy records of a health maintenance organization between 1999 and 2010. The study showed a 68% decrease in the risk of hepatocellular carcinoma among patients who were using statins for less than 2 years VITALS Key clinical point: Statin use may signifcantly reduce the risk of hepatocellular carcinoma. Major fnding: Statin use for less than 2 years is associated with a signifcant 68% decrease in the risk of hepatocellular carcinoma, and a 69% decrease among patients using them for more than 2 years, compared with nonusers. Data source: A nested case-control study among 94 cases of hepatocellular carcinoma matched to 468 controls. Disclosures: No conficts of interest were declared. and a 69% decrease among patients who were using statins for more than 2 years, compared with nonusers, according to the investigators. The study was published online Aug. 8 in the journal Cancer Epidemiology (dx.doi.org/10.1016/j. canep.2014.06.009). [email protected]      LIVER DISEASES GIHEP NEW S. COM • OCT OBE R 2014 29 TURQUOISE regimen active against HCV+HIV BY ALICIA AULT Frontline Medical News WASHINGTON – Early studies show that a new, combined antiviral regimen seems to suppress hepatitis C viremia while keeping HIV viremia stable in coinfected patients. Dr. Joseph Eron presented phase II data from 63 patients who were enrolled in TURQUOISE-I. A total of 94% (59/63) of patients achieved a sustained virologic response (SVR) 12 weeks after completing 12 weeks of therapy, and 61 of 63 patients achieved an SVR 4 weeks after completing 12 or 24 weeks of therapy, Dr. Eron reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. The regimen included ABT-450 (an NS3-4A protease inhibitor that was identifed by AbbVie and Enanta), which was combined with ritonavir and ombitasvir (another AbbVie drug, also known as ABT-267) into a single tablet, plus dasabuvir (ABT333) and ribavirin. Ombitasvir is an NS5A inhibitor and dasabuvir is a nonnucleoside NS5B polymerase inhibitor. To be included in TURQUOISE-I, patients have to be aged 18-70 years; be treatment naive or have previous pegylated interferon/ribavirin treatment experience; have hepatitis C virus (HCV) genotype 1 infection; have plasma HIV-1 RNA less than 40 copies/mL; and be taking a stable, qualifying HIV-1 antiretroviral therapy regimen, said Dr. Eron, a professor of medicine at the University of North Carolina, Chapel Hill. Patients with cirrhosis are not excluded, but will not be enrolled if they have had prior therapy with direct-acting antivirals for HCV, or any current or past clinical evidence of liver decompensation. All patients will be followed for 48 weeks after therapy is stopped. Thirty-one patients were given therapy for 12 weeks and then assessed for SVR at 12 weeks. Thirty-two patients were given therapy for 24 weeks and assessed 4 weeks later. Patients also were evaluated for end-of-treatment response, on-treatment virologic failure, and posttreatment HCV viral relapse. At baseline, 59 patients in each arm were male, and 16 were African American. The mean age was 51 years. Six patients in each arm (19%) VITALS Key clinical point: A new therapy is on the horizon for HCV-HIV coinfected patients that achieves high virologic response with few severe side effects. Major fnding: A three-drug regimen that includes ABT-450 and ombitasvir in one pill, plus dasabuvir and ribavirin, achieved high SVR in patients coinfected with HCV GT1 and HIV. Data source: A 63-patient, two-arm, open-label prospective study. Disclosures: The study was sponsored by AbbVie. Dr. Eron received grant and research support from, and/or served as a consultant to, AbbVie, Bristol-Myers Squibb, and other companies. Other authors had numerous additional disclosures. had cirrhosis. A high proportion in each arm (53/63 in the 12-week and 49/63 in the 24-week arm) had the interleukin-28B genotype, which is known to indicate a much harder-totreat disease, Dr. Eron said. At the end of treatment, only one patient in each arm was not responsive. Four weeks post therapy, 29 of 31 patients in the 12-week arm and 31 of 32 patients in the 24-week arm had an SVR. Two patients had virologic failure. Both had been unresponsive to previous therapies, and both had the IL-28B genotype and resistance-associated variants at the time of failure. No patient withdrew because of adverse events, but about 90% (57/63) experienced some side efect, with the most common being fatigue and insomnia. Six patients had to reduce their ribavirin dose because of a drop in hemoglobin levels, but they were still responsive to therapy. Five patients had a confrmed increase in HIV RNA higher than 40 copies/mL, but not above 200 copies/mL, said Dr. Eron. And all the patients remained suppressed on the same HIV regimen and without interrupting their HCV therapy, he said. Soon, a cohort of patients on stable darunavir antiretroviral therapy will be enrolled and given the three-drug HCV regimen for 12 weeks. The full global TURQUOISE study will begin later in 2014, Dr. Eron said. [email protected] On Twitter @aliciaault 30 ENDOSCOPY, PANCREAS & BILIARY TRACT O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S Post–LRYGB cholecystectomy most common BY BIANCA NOGRADY Frontline Medical News T he overall rate of cholecystectomy after weight-loss surgery is low, but it is more likely to occur among patients who experience excessive weight loss following their procedure and those who undergo laparoscopic Roux-en-Y gastric bypass. Analysis of prospective data from 1,398 patients undergoing bariatric surgery showed an overall cholecystectomy rate of 7.8% over a median follow-up of 49 months, with the frequency higher in the frst 6 months, according to data published in Surgery for Obesity and Related Diseases. Cholecystectomy rates were signifcantly higher among individuals who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB), compared with those who received a laparoscopic adjustable gastric band (LAGB) or laparoscopic sleeve gastrectomy (LSG) (10.6% vs. 2.9% vs. 3.5%, P = .001). “Although the LRYGB was the procedure associated with the highest rate of cholecystectomy, the present study found that this relationship was due to the superior %EWL [percent excess weight loss] associated with this procedure, compared with the LAGB and LSG procedures,” wrote the late Dr. Victor B. Tsirline of Northwestern Memorial Hospital, and his colleagues. Patients who lost more than a quarter of their weight within 3 months of surgery showed signifcantly higher rates of cholecystectomy, and there was a 25% increase in cholecystectomy per 10% of excess weight loss within the frst 3 months after weight-loss surgery, although this association was signifcant only among patients treated with gastric bypass (Surg. Obes. Relat. Dis. 2014;10:313-21). There were statistically signifcant diferences in cholecystectomy rates performed by the three surgeons involved, although again, this was only in patients who had undergone gastric bypass, and researchers said this could be partly attributed to the fact that one surgeon saw a greater proportion of revision patients. Researchers also noted an interaction with race, as black patients had signifcantly lower rates of cholecystectomy, compared with white patients (2.2% vs. 8.9%, P = .0001), and Native American patients showed the NEW WEEKLY QUIZZES! Build your knowledge through 5-question quizzes from GI & Hepatology News! Each week a new quiz on a topic related to the feld of gastroenterology and hepatology will be posted. Take as many quizzes as you want—they’re all free. Challenge yourself further by taking quizzes in other specialties! www.gihepnews.com/md-iq-quizzes highest rates of all (65%). This study found no diference in cholecystectomy rates between patients taking ursodiol and those who weren’t. Rapid weight loss after bariatric surgery is associated with an increased risk of gallstones, and routine cholecystectomy at the time of bariatric surgery has been the subject of considerable debate. Those in favor argue that it prevents the morbidity of symptomatic cholelithiasis and avoids the risk of duct stones which can be difcult to treat after gastric bypass. However opponents say routine cholecystectomy would prolong hospital stays, lengthen operating times, and potentially increase complication rates, when the use of ursodiol after weight-loss surgery has been shown to decrease the frequency of gallstones. “The fndings of the present study indicate that a conservative approach to cholecystectomy ... is warranted, because only 7.8% of patients developed symptomatic gallbladder disease within 4 years on average,” researchers wrote. “Furthermore, there are technical advantages of delayed cholecystectomy that stem from reduced intra-abdominal fat content and decreased liver size secondary to weight loss.” There were no conficts of interest declared. [email protected] CLINICAL CHALLENGES AND IMAGES The diagnosis Answer to “What’s your diagnosis?” on page 2: Tuberculosis diagnosed by endoscopic ultrasonography with fne-needle aspirate E ndoscopic ultrasonography visualized a heterogeneous perigastric mass abutting the gastric cardia and extending down to, but not invading, a normal-appearing pancreas. Fine-needle aspiration of the mass demonstrated necrotizing granulomas with acid-fast bacilli. A chest x-ray was negative for any cavitary lesions. The patient was started on antituberculosis therapy with resolution of his pain shortly afterward. Six months later, repeat computed tomography of the abdomen and pelvis showed an interval decrease in size of the perigastric mass (2.6 × 2.0 × 1.6 cm). He has since then completed a total of 9 months of medical therapy and remains asymptomatic. This is an unusual presentation of tuberculosis as an isolated perigastric mass. The presence of gastric acid and the paucity of lymphoid tissue make the stomach the least likely area of the gastrointestinal tract to be afected by tuberculosis.1 Gastroduodenal tuberculosis is thought to present in three ways: most commonly gastric outlet obstruction, upper gastrointestinal hemorrhage from a tubercular ulcer, and more rarely as a gastric or periampullary mass. Complications such as fstulae formation may also arise. Our patient presented with epigastric discomfort, and this can be the initial presenting symptom in up to 56.5% of cases.2 Conventional endoscopic biopsy has poor diagnostic yield,2 although fne-needle aspiration guided by either computed tomography or endoscopic ultrasonography may produce better results. We suspect local extension from regional lymph nodes to be the cause of the perigastric mass, but hematogenous spread and swallowing of organisms may also precipitate gastric tuberculosis. Perforation has been reported rarely,3 and treatment entails conventional tuberculosis therapy, as our patient received. In cases of obstruction, fstulae, or persistent ulceration, surgical management may be considered. References 1. Tromba, J.L., Inglese, R., Reiders, B., et al. Primary gastric tuberculosis presenting as pyloric outlet obstruction. Am. J. Gastroenterol. 1991;86:1820-2. 2. Rao, Y.G., Pande, G.K., Sahni, P., et al. Gastroduodenal management guidelines, based on a large experience and a review of the literature. Can. J. Surg. 2004;47:364-8. 3. Sharma, D., Gupta, A., Jain, B.K., et al. Tuberculosis gastric perforation: report of a case. Surg. Today 2004;34:537-41. [email protected] ENDOSCOPY, PANCREAS & BILIARY TRACT GIHEP NEW S. COM • OCT OBE R 2014 31 After 3-year stumble, new weight-loss drug wins BY MICHELE G. SULLIVAN Frontline Medical News A fter a delay of more than 3 years, the Food and Drug Administration has approved the nation’s third weight-loss drug, a combination of naltrexone and bupropion. The extended release tablets (Contrave; Orexigen and Takeda) are approved for use in adults who have a body mass index of at least 30 kg/m2, or those with a BMI of at least 27 kg/m2 and at least one additional weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. The agency recommended that Contrave be used in addition to caloric restriction and increased physical activity. Dr. Timothy Garvey, chair of the American Association of Clinical Endocrinologists’ scientifc committee, lauded the approval. He said Contrave will be a valuable addition to the existing weight-loss medications: the phentermine/topiramate combo (Qsymia; Vivus) and lorcaserin (Belviq; Arena). “There are no head-to-head trials with the other drugs, so we really can’t say much about relative efcacy,” said Dr. Garvey who is also chair of the department of nutrition at the Univer- sity of Alabama at Birmingham, “But when you look at the placebo-subtracted weight loss in all the phase III data, it looks like Contrave is in the middle, with about a 6% loss over lifestyle interventions alone. So it’s not as efective as the topiramate combination, but more efective than lorcaserin.” In the pivotal, 56-week phase III trials, those taking Contrave lost 5%8% of their baseline body weight, compared with a loss of 1%-2% in those on placebo. The proportion of those who lost at least 5% of their baseline body weight ranged from 45% to 56% of those on the proposed dose, compared with 16%-43% of those on placebo. FDA guidance on weight-loss drugs suggests a 12-week efcacy evaluation – if the patient has not lost at least 5% of total body weight by then, the drug should be discontinued and another started. Because it contains bupropion, an antidepressant linked to suicidal risk, the drug carries a black box warning. Bupropion is also known to lower seizure threshold, so the drug should not be used in patients with seizure disorders. If a seizure occurs while taking the medication, it should be permanently discontinued. Orexigen and Takeda originally brought the drug forward in December 2011. It was not approved at that time because of concerns about its efect on blood pressure – an unexpected move, and one that Orexigen management called “a big setback.” About a quarter of those in the 56-week pivotal phase III trial experienced signifcant blood pressure increases of at least 10% above their baseline, compared with about 20% of those in the control arm. Increases of diastolic blood pressure of at least 5 mm Hg over baseline occurred in 37% of those on the combination, compared with 29% of those on placebo. About a quarter in the active arm also had heart rate increases of at least 10 beats per minute, compared with 19% of those taking placebo. Because of these concerns, the FDA required the companies to conduct a large, double-blinded randomized, placebo-controlled trial to investigate the risk of major cardiovascular events. Takeda and Orexigen then launched the 4-year, 8,900 patient Light study, which is still ongoing. Endpoints are major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) in overweight and obese subjects who have concomitant diabetes and/or other cardiovascular risk factors. In June, citing encouraging preliminary results, Takeda and Orexigen brought Contrave to the FDA once more – only to be shot down again, at least temporarily. The agency required a review extension in order to come to agreement on the fnal form of postmarketing surveillance, said Denise Powell, a spokeswoman for Orexigen. “At that time, FDA said the data looked good,” she said in an interview. “We just needed more time to work out the postmarketing requirements.” These will include a cardiovascular outcomes trial, studies in pediatric patients, and clinical trials to evaluate dosing in patients with hepatic or renal impairment. Dr. Garvey is a consultant for Daiichi Sankyo, LipoScience, Takeda, Vivus, Boehringer Ingelheim, Janssen, Eisai, and Novo Nordisk. He has received research funding from Merck, AstraZeneca, Weight Watchers, Eisai, and Sanof. [email protected] On Twitter @alz_gal May 16–19, 2015 WHERE MEDICINE MEETS INNOVATION Exhibit Dates: May 17–19, 2015 Washington, DC Walter E. Washington Convention Center www.ddw.org Get Noticed. Join the effort in providing the latest research to health-care professionals in gastroenterology, hepatology, GI endoscopy and GI surgery. Share your work at the world’s largest gathering of leaders in the field of digestive diseases. DDW® is the premier educational forum for digestive disease professionals. Year after year, thousands of GI academicians, clinicians, researchers and students attend the meeting to witness innovative advances in basic, clinical and translational research. Accepted abstracts will be published in the April 2015 online supplement to GIE: Gastrointestinal Endoscopy or the April 2015 online supplement to Gastroenterology. To submit your abstract, view informational videos, read submission guidelines and get answers to frequently asked questions, visit www.ddw.org/abstracts. CALL FOR ABSTRACTS Submit your abstract at www.ddw.org/abstracts THE ABSTRACT SUBMISSION PERIOD: BEGINS: Tuesday, Oct. 21, 2014 at 9 a.m. ET ENDS: Tuesday, Dec. 2, 2014 at 9 p.m. ET 32 POSTGRADUATE COURSE O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S A G A S P R I N G P O S T G R A D U AT E C O U R S E These presentations were given at Digestive Disease Week® 2014 in Chicago Colon section prep completion and performance of colonoscopy improves bowel prep quality. Dr. Sameer Saini rehe colon course brought us numerous pearls, viewed additional system-level factors to improve from how to perform quality endoscopy safe- ADRs, such as high-defnition and wide-angle ly, to providing updates on genetic colonoscopes, high-quality withdrawal screening for colon cancer syndromes techniques, and colonoscope adjuncts and fecal microbiota transplant. such as caps, chromoendoscopy, and narQuality colonoscopy is not just an row-band imaging. efort to provide the best care to our A quality endoscopy is also a safe enpatients; it will become a barometer doscopy, and Dr. Neena Abraham providfor not only government and private ed numerous “cardiogastroenterology” payers, but also patients looking for toppearls to help guide care of patients with notch care. Adenoma detection rate is gastrointestinal diseases requiring endosan objective parameter that we should copy during anticoagulant and antiplateDR. EARLY monitor regularly and strive to meet or let therapy. If you remember one key exceed national benchmarks. point from her talk, it should be: Do not We learned from Dr. Thomas Imperiale that stop aspirin for endoscopy. advances in bowel preparation have led to resulA major goal of colonoscopy is adenoma detectant improvements in adenoma detection rate tion and removal, and Dr. Joseph Elmunzer guided (ADR). We now know that split preparations are us through techniques to tackle the “defant polmost efective, and minimizing the time between yp,” including submucosal injection, proper coloBY DAYNA EARLY, M.D. T noscope positioning, clip closure of defects, and the importance of complete adenoma resection. When we fnd adenomas and cancers, we should be vigilant in inquiring about the patient’s family history, and be mindful of patterns suggestive of a hereditary cancer syndrome such as a large number of adenomas, right-sided sessile serrated adenomas, and family members with colorectal neoplasia at a young age. Dr. Elena Stofel reviewed clinical features of common hereditary syndromes. Dr. Lawrence Brandt reviewed treatment of refractory or recurrent Clostridium difcile infection. He discussed therapy with fdaxomicin, which has been shown to be superior to vancomycin for C. difcile recurrence, and provided an overview of the process of fecal microbiota transplant. Dr. Early is professor of medicine, Washington University, St. Louis. [email protected] Esophagus/upper GI section BY HERBERT C. WOLFSEN, M.D., FASGE O ne highlight of the AGA Postgraduate Course was the esophageal disease session. The presentation by Dr. Michael B. Wallace summarized recent studies using advanced imaging modalities in patients with Barrett’s esophagus. Studies using chromoscopy and virtual chromoscopy techniques such as narrow-band imaging have increased the detection of dysplasia in BE patients. These are so-called red fag techniques that image large areas of mucosa to detect mucosal abnormalities suspicious for the presence of dysplasia or neoplasia. Endomicroscopy describes the use of real-time, targeted endoscopic imaging modalities that are capable of producing histologic-like images of mucosa at depths up to 200 microns. Confocal laser endomicroscopy (CLE) uses a blue light laser (405 nm) and collimated light detection and analysis to produce 1,000-fold magnifed images. When used with a fuorescent contrast agent such as fuorescein or acrifavin dye, these systems produce cellular-level images that are comparable to those images seen with optical microscopy. Further, a multicenter study will soon begin using a tethered-capsule (nonendoscopic) form of volumetric laser endomicroscopy as a method to screen for BE. Dr. Amitabh Chak expanded on doscopic testing was reviewed, inthese issues and reviewed those surcluding the diferential diagnosis of rounding screening and surveillance lymphocytic duodenosis with use of of BE patients for the early detecnonsteroidal anti-infammatory drugs tion and treatment of esophageal (NSAIDs), Helicobacter pylori infecadenocarcinoma. This presentation tion, Crohn’s disease, and Sjogren’s suggested that necessary future imsyndrome. Proper duodenal biopsy provements include cost-eftechnique was emphasized fective advanced imaging with two forceps biopsy techniques optimized for samples obtained from the use in clinical practice, moduodenal bulb and four lecular biomarker panels biopsy samples obtained for prediction of which from the second portion patients may progress to of the duodenum. Also dysplasia and neoplasia, discussed was the utility and high-quality intensive of HLA typing for DQ2/8 endoscopic surveillance for in patients currently using DR. WOLFSEN high-risk BE patients. a gluten-free diet, patients Dr. Joe Murray’s comprewith negative serology rehensive presentation of celiac disease sults but abnormal duodenal biopsy described the protean clinical presenfndings, and those with negative tations of this disease as well as optiserology results who are at increased mal use of serologic and endoscopic genetic risk. testing. Celiac disease is increasingly Dr. James Scheiman discussed manidentifed in middle-aged patients agement of the complex interaction (median 45 years) without diarrhea. and risks associated with the use of Classic malabsorption symptoms of NSAIDs, aspirin, clopidogrel, and diarrhea, weight loss, steatorrhea, proton pump inhibitors in the setting and nutritional defciencies are found of previous ulcer disease, gastrointesin 25% of patients. Half of celiac tinal bleeding, and H. pylori infection. patients will have only one symptom Results from randomized controlled such as anemia, diarrhea, lactose studies and observational studies intolerance, or weight loss. Nongaswere the basis for the Consensus trointestinal symptoms are present in Group to recommend the use of PPI another 25% of patients such as infer- therapy as the GI bleeding protective tility, bone disease, chronic fatigue, or strategy of choice. PPI therapy was abnormal liver enzyme test results. also recommended as cost-efective Optimal use of serologic and entreatment for aspirin-using patients, although the risks and benefts of long-term PPI treatment require patient education and individualization. Finally, Dr. Rhonda Souza discussed eosinophilic esophagitis, a chronic immune/antigen-mediated esophageal disease characterized by symptoms related to esophageal dysfunction associated with eosinophil-predominant infammation such as dysphagia, food impaction, chest pain, heartburn, abdominal pain, and refractory refux dyspepsia. Endoscopic features include the ringed esophagus, white specks, linear furrows, and stricture. Histologic features of EoE are eosinophilia (more than 15 intraepithelial eosinophils per high-power feld), basal zone hyperplasia, and dilated intercellular spaces. These eosinophils are activated via T-helper 2 immune system via interleukins-4, -5, and -13. Treatment of EoE usually requires use of PPIs. The use of topical corticosteroids and endoscopic dilation for symptomatic strictures may also be necessary. Nondrug treatment approaches such as the six food elimination diet of the most common food allergens such as milk, soy, eggs, wheat, nuts, and seafood have also been successful. Dr. Wolfsen is in the division of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla. [email protected] POSTGRADUATE COURSE GIHEP NEW S. COM • OCT OBE R 2014 33 A G A S P R I N G P O S T G R A D U AT E C O U R S E These presentations were given at Digestive Disease Week® 2014 in Chicago Pancreatic-biliary section BY GRACE H. ELTA, M.D. AGAF I n the frst presentation, on benign biliary strictures, Dr. Greg Cote divided etiologies into extrinsic vs. intrinsic and noted which ones require only bridging plastic stents while treating the underlying cause. The etiologies that require endoscopic therapy include chronic pancreatitis, postoperative (both postcholecystectomy and posttransplant), primary sclerosing cholangitis, and the rare common bile duct stone–induced stricture. For primary sclerosing cholangitis, dilation alone is usually sufcient and safer than dilation plus stenting. Strictures that are postoperative or due to chron- ic pancreatitis require endotherapy combining dilation and placement of the maximal number of plastic stents possible. Dr. David Lichtenstein gave a talk on bile duct strictures. He discussed the multiple diagnostic methods needed to determine whether a stricture is benign or malignant. At endoscopic retrograde cholangiopanDR. ELTA creatography it is useful to combine both brush cytology (+/– FISH) and intraductal biopsy. Higher sensitivities are obtained by utilizing endoscopic ultrasound (EUS)/ fne-needle aspiration (FNA), although Hepatology section alcoholic steatohepatitis. By careful estimates, he predicts that there may he hepatology session had a be as many as 25 million patients in range of excellent topics for the the U.S. with NASH. New treatments practicing gastroenterologist/ are being developed, but we are hepatologist. Perhaps the area chang- still a long way from having reliable ing most rapidly is that of treatments for this disease. treatment of hepatitis C. Thus, lifestyle modifcations Dr. Jordan Feld presented with judicious weight loss “Choosing the optimal and exercise regimens reHCV regimen.” He highmain the most important lighted the recent approval treatments available for of simeprevir and sofosNASH/NAFLD. Dr. Harbuvir both with pegylated rison also highlighted the interferon and ribavirin for recent studies that demontreatment of chronic hepstrate that regular cofee DR. BACON atitis C genotype 1. HCV consumption may be helpcure rates of 80%-90% ful for reducing fbrosis in were described. He also told us about patients with NAFLD. exciting developments with interferDr. Jorge Marrero presented data on-free regimens that will be availon kidney injury in cirrhosis and how able in October/November of 2014. to diferentiate acute kidney injury The combination of sofosbuvir from hepatorenal syndrome. Finally, and ledipasvir and the combination Dr. Sam Lee taught us to recognize of three direct-acting antiviral agents that cirrhosis is not a hypocoagulable with or without ribavirin will revostate and that there are situations lutionize our care of hepatitis C pawhere anticoagulant therapy in cirtients from now on. Many clinicians rhosis is defnitely a beneft. The idea have already been using interferof using anticoagulation in patients on-free regimens by combining sime- with cirrhosis is counterintuitive to previr and sofosbuvir for 12 weeks many of us, but Dr. Lee presented with excellent results. data to endorse this approach. Dr. Michael Lucey from the University of Wisconsin School of Medicine Dr. Bacon is the James F. King MD Enand Public Health talked about the dowed Chair in Gastroenterology, profesmanagement of alcoholic hepatitis. sor of internal medicine, and director of Dr. Stephen Harrison from Brooke abdominal transplantation at Saint Louis Army Medical Center presented imUniversity School of Medicine, division of pressive data on the huge number of gastroenterology and hepatology, St. Louis. patients that we will be seeing with [email protected] nonalcoholic fatty liver disease/nonBY BRUCE R. BACON, M.D., AGAF T if the patient is a resection or transplant candidate, some surgeons are fearful of tumor seeding with FNA. Other techniques discussed included cholangioscopy and probe-based confocal microscopy. The pros and cons of various palliative stents were also discussed, as were experimental endoscopic therapies including photodynamic therapy and endobiliary radiofrequency ablation. Dr. Robert Hawes discussed the management of chronic pancreatitis pain with medical, endoscopic, and surgical therapy. He reviewed the causes of pain in chronic pancreatitis, the variable clinical presentations (due to main pancreatic duct obstruction or ongoing infammation), and the fact that placebo response rates are high. Medical therapies, including pancreatic enzymes, antioxidants, and octreotide are not well proven although often tried. Celiac axis blockade has at best a short-lived, 50% chance of beneft. Endoscopic therapy (often combined with extracorporeal shock wave lithotripsy has some efcacy for obstructive disease. Surgery is most efective for obstructive disease, but resection carries the risk of insulin dependence. Dr. Martin Freeman discussed acute idiopathic recurrent pancreatitis and its likely multifactorial causes with interaction of genetic, anatomic, and environmental factors. He noted the overlap presentation of acute pancreatitis with chronic pancreatitis. He said EUS has a key diagnostic role, as does secretin-stimulated magnetic resonance cholangiopancreatography. The controversial role of endoscopic therapy was discussed. Dr. Elta is professor of internal medicine, University of Michigan, Ann Arbor. [email protected] PRACTICE ECONOMICS 34 O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S AMA calls on vendors, feds to improve EHRs BY MARY ELLEN SCHNEIDER Frontline Medical News W ith more physicians reporting that electronic health records are more of a hindrance than a help, the American Medical Association is calling on vendors and federal health ofcials to make changes that will improve the usability of electronic systems. The AMA released eight priorities for improving physician usability of EHRs. But Dr. Steven J. Stack, the AMA’s president-elect, who is an emergency physician in Lexington, Ky., said the most helpful frst step would be for federal ofcials to add more fexibility to the so-called meaningful use program, which requires physicians to meet requirements for the clinical use of their EHRs, such as meeting benchmarks for electronic prescribing or communicating with patients via an online portal. The AMA is asking the Centers for Medicare & Medicaid Services, which oversees the meaningful use program, to lower the thresholds for earning incentives and penalties. Currently, physicians must meet 100% of the meaningful use standards to earn The most helpful frst step would be for federal offcials to add more fexibility to the meaningful use program. DR. STACK the bonus payment and avoid a penalty. The AMA wants physicians to be able to avoid penalties by meeting half of the requirements. But vendors also have a role to play, according to the AMA. Dr. Stack said during a Sept. 16 news conference to announce the new AMA framework that most currently available systems aren’t customized with displays for individual specialties, ask for too much data entry from physicians, and require excessive scrolling and clicking. The AMA has set eight priorities for improving EHR usability, developed by an advisory committee of physicians, experts, researchers, and health IT executives. The priorities include: ▶ Enhancing physicians’ ability to provide high-quality patient care. ▶ Supporting team-based care. ▶ Promoting care coordination. ▶ Ofering product modularity and confguration. ▶ Reducing cognitive workload. ▶ Promoting data liquidity by allowing data to be shared between diferent settings. ▶ Facilitating digital and mobile engagement. ▶ Expediting user input into produce design and postimplementation feedback. The AMA’s call to action comes in the midst of National Health IT week, which features a week of events with IT vendors, federal ofcials, health care providers, and other groups focused on advancing health through the use of electronic systems. [email protected] On Twitter @maryellenny PRACTICE ECONOMICS GIHEP NEW S. COM • OCT OBE R 2014 PRACTICE MANAGEMENT TOOLBOX: BY JOANNA GIBSON, M.D., JILL LACY, M.D., ELLEN MATLOFF, M.S., AND MARIE ROBERT, M.D. This month we continue last month’s theme that focused on the role of pathology in the care of our GI patients. Many gastroenterologists have successfully incorporated pathology into their core practices either within a business infrastructure or as part of a larger health care system. Dr. Gibson and her colleagues at Yale University School of Medicine have helped inform us about a particularly difcult management problem: how to handle the genetically highrisk patients we see frequently in our hospitals and endoscopy units. New comprehensive practice guidelines concerning management of hereditary colon cancer syndromes are in development, but this article provides a clear and concise guide for the practicing gastroenterologist. John I. Allen, MD, MBA, AGAF, Special Section Editor A s health care reform progresses, the pressure to more closely integrate clinical service lines such as colorectal cancer management has intensifed. The practicing gastroenterologist may fnd that they are not equipped to understand pathology information required for coordinated team-based care of their patients. This is especially true in the case of molecular classifcation of CRC, something that has become a standard component of comprehensive oncologic care and has been incorporated into many gastroenterology practice pathology services. Molecular characterization not only provides insight into the pathogenesis of cancer but has prognostic and therapeutic implications. This review is a practical guide to the most common molecular tests used in what has become standard GI practice. Molecular classifcation of colorectal cancer The molecular classifcation of colon cancer is based on the cumulative study of precursor lesions (such 35 Microsatellite instability testing as adenomas and sessile serrated polyps), inherited colon cancer syndromes (such as familial adenomatous polyposis syndrome and Lynch syndrome/hereditary nonpol- sporadic dMMR/MSI cancers is believed to be the sessile serrated polyp, an epithelial proliferation characterized by the V600E BRAF mutation. Therefore, sporadic dMMR/MSI DR. GIBSON MS. MATLOFF DR. LACY yposis colon cancer), and molecular profling of colorectal cancers. Broadly, colorectal cancers are divided into two general groups based on genomic diferences: chromosomal instability, accounting for 75%-80% of all colorectal cancers, and microsatellite instability (MSI), accounting for 15%-20% of all colorectal cancers.1,2 Inherited colorectal susceptibility syndromes are estimated to account for approximately 1%-2% of the MSI cancers and less than 1% of chromosomal instability cancers. Microsatellite instability pathway MSI is defned by changes of microsatellite length (repetitive noncoding DNA sequences) resulting from defcient mismatch repair (dMMR) during DNA replication.1,3,4 The protein complex responsible for mismatch repair function is a tetramer composed of two heterodimers: MLH1/PMS2 and MSH2/MSH6.4 The expression of each protein in a heterodimer is dependent on its partner, such that if one protein is absent, the partner protein consequently is degraded. When this occurs, the heterodimer is not available to form a functional tetramer and dMMR, as manifested by MSI, is the result. Most dMMR/MSI cancers occur sporadically and are associated with the loss of MLH1 expression owing to epigenetic silencing of the MLH1 gene promoter via CpG island methylation.1,2 The precursor lesion of Content from this column was originally published in the “Practice Management: The Road Ahead” section of Clinical Gastroenterology and Hepatology (2014;12:171-6). “Practice Management Toolbox” provides key information and resources necessary for facing the unique challenges of today’s clinical practices. Resources for Practical Application: To view additional online resources about this topic and to access our Coding Corner, visit, www/cghjournal.org/ content/practice_management. DR. ROBERT cancers also frequently harbor the V600E BRAF mutation.5 Approximately 1%-2% of dMMR/ MSI cancers occur in the setting of Lynch syndrome as a result of a hereditary gene defect in one of the four MMR genes.6,7 The most frequently mutated gene in Lynch syndrome patients is MSH2 (40%), followed by MLH1 (30%). MSH6 and PMS2 are mutated at lesser frequencies, approximately 15% each. In contrast to the sporadic setting, dMMR/ MSI cancer in Lynch syndrome patients arises from adenomas without BRAF mutations. Therefore, cancers in Lynch syndrome patients will have a wild-type BRAF gene.5 Methods of dMMR/MSI detection dMMR is detected by immunohistochemistry (IHC) and MSI is detected by polymerase chain reaction (PCR).3,8 PCR involves extraction of DNA from a tumor followed by DNA amplifcation of microsatellite markers, and determination of the amplifed microsatellite lengths as compared with nontumor DNA from the same patient. Although laboratories vary with regard to the number of microsatellites tested, most use a standard set of fve microsatellite markers. A tumor is classifed as MSIhigh if two or more of the fve microsatellite markers show instability, as MSI-low if only one of fve markers is unstable, and as microsatellite stable (MSS) if the microsatellite markers show no expansion.3,8 The IHC method uses antibodies directed against each MMR protein to detect the expression of the proteins in the tumor cells.3 In cancers with dMMR/MSI, loss of nuclear expression of MMR proteins is seen in the cancer cells. In contrast, nonneoplastic cells, such as lymphocytes or adjacent colonic mucosa, show preserved nuclear expression of the MMR proteins, irrespective of the hereditary or sporadic setting. The nonneoplastic cells therefore serve as an important internal control for the IHC procedure. Most laboratories test each of the four MMR proteins. The majority of dMMR/MSI cancers show loss of expression of both MMR proteins in a heterodimer (either MLH1/PMS2 or MSH2/MSH6) in the cancer cells, with preserved expression of the other heterodimer. In sporadic dMMR/ MSI cancers, loss of MLH1/PMS2 expression is characteristic, whereas in Lynch syndrome either heterodimer may be lost.3,6 Occasionally, unusual IHC patterns exist, usually in the setting of Lynch syndrome, such as isolated loss of MSH6 in 10% of cancers or isolated loss of PMS2 in approximately 5% of cancers.6 Polymerase chain reaction vs. immunohistochemistry The results obtained from PCR and IHC studies are complementary but provide diferent information.3,7 The PCR method does not detect which protein in the mismatch repair tetramer is defcient. Therefore, PCR cannot distinguish between sporadic or Lynch syndrome associated dMMR/MSI cancer. IHC, on the other hand, provides specifc mismatch repair protein expression data and can suggest etiology. Loss of MSH2/ MSH6 suggests Lynch syndrome, whereas loss of MLH1/PMS2, although seen in Lynch syndrome, is characteristic of the more common sporadic dMMR/MSI cancer.6 When present, abnormal IHC results also can be used to guide gene sequencing in patients with a high risk of Lynch syndrome. If the nuclear protein expression of all four MMR proteins is intact, the tumor is assumed to be MSS, with rare exceptions, and PCR may not be needed except in patients at high risk for Lynch syndrome. IHC is inexpensive, is widely available in most pathology laboratories, and can be performed on both biopsy specimens and resection specimens, usually within 1-2 days. In the majority of cases, interpretation of IHC expression is straightforward and requires little training. False-negative results occur in less than 10% of Lynch syndrome patients with mutations that lead to protein dysfunction with preserved immunoreactivity.4 PCR analysis is performed on tissue removed from a tissue block containing an adequate tumor sample (at least 30% of the tissue within the block consisting of tumor) for DNA extraction, as well as accompanying Continued on following page PRACTICE ECONOMICS Continued from previous page normal tissue for comparison. Biopsy samples may not contain sufcient tumor volume for PCR, whereas most resections are sufcient. The turnaround time for PCR is 5 days to 2 weeks. When to test and which specimen It now generally is accepted that all patients with colorectal cancer should be tested for MSI/dMMR using either IHC, PCR, or both at some point during the evaluation and treatment of their cancer, regardless of their age.3,9 Published guidelines, such as the 2004 Revised Bethesda guidelines and the Revised American College of Gastroenterology 2008 guidelines, are aimed at detecting Lynch syndrome patients postoperatively.7,10 However, testing of biopsy material before surgical resection has been advocated by some and has become standard practice in many institutions. At least two updated guidelines are in process, one by the U.S. Multi-Society Task Force on Colorectal Cancer and one by the American Gastroenterological Association Institute ( John I. Allen, MD, personal communication). Testing of cancer in the setting of neoadjuvant chemoradiation treatment can be challenging because O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S marked therapy responses limit the amount of cancerous tissue available for DNA extraction. Residual tumor volume may be sufcient for IHC analysis. Pitfalls exist; neoadjuvant therapy has been reported to induce MSH6 loss in 20% of colon cancers.11 In this setting, comparison with PCR results or prior biopsy samples may be needed. In addition to testing cancer tissue, dMMR/MSI testing also can be performed on adenomatous tissue in patients with a high risk of having Lynch syndrome based on clinical criteria.12 However, in this setting, the interpretation of intact MMR expression by IHC should not be used as evidence against the possibility of Lynch syndrome because MMR Figure 1. Mismatch repair immunohistochemistry algorithm. loss is speculated to occur as a late event in the adenoma-carcinoma sequence. Initiation of genetic counselors. Decisions regard- 1), the patient most likely does not ing which test to use (IHC, PCR, or dMMR/MSI testing is best achieved have Lynch syndrome. Outside of through a coordinated efort between both) are center dependent. There is this scenario, patients whose tumors clinicians (gastroenterologists, oncol- a trend at many centers to begin with are MSI-high and/or show abnormal IHC for dMMR, reserving PCR anal- IHC should be referred to a certifed ogists, surgeons), pathologists, and ysis for specifc situations (Figure 1). genetic counselor for informed consent to undergo diagnostic germline Indications for dMMR/MSI testing testing for mutations in the Lynch Tissue testing for dMMR/MSI serves genes (Figure 1). I two clinically important functions: Informed consent before tumor to screen for Lynch syndrome and testing has been raised as an ethical to provide prognostic information issue15; however, it is not currently regardless of syndrome status. In required because tumor testing is addition, although beyond the scope simply a screen for Lynch syndrome. of this review, MSI testing is also inIt is advised that clinicians prepare creasingly used in other investigative patients for the possibility that if contexts, such as to predict theratheir tumor screen is positive, they peutic response to 5-fuorouracil. For then will be referred for genetic these reasons, and because the Amcounseling and testing. sterdam and Bethesda criteria have Tumor screening and genetic testfailed to serve as efective screens for ing for Lynch syndrome is critical in Lynch syndrome, determination of preventing additional primary maligdMMR/MSI now is recommended in nancies in the patient, and in testing all colorectal tumors.13 and providing appropriate surveillance and risk reduction to family Relevance to Lynch syndrome members. However, a recent study dMMR/MSI detection serves solely showed that surgeons referred fewer as a screen for Lynch syndrome, and than half of their patients with highare not by themselves diagnostic. risk tumors for genetic testing.6 This represents not only a subIn addition, each test will miss 5%15% of all cases of Lynch syndrome. stantial liability risk for clinicians and their institutions, but a waste Therefore, a negative tumor screen of health care dollars and a potenshould not negate a referral to genetic counseling if the personal and/ tially life-saving lost opportunity for patients and their families. At some or family history is suggestive of centers genetic counselors review a hereditary cancer syndrome.14 If IHC shows loss of MLH1 and PMS2 all MSI testing, including follow-up expression, BRAF analysis should be methylation/BRAF testing, to ensure performed. If a V600E BRAF mutacorrect interpretation and to increase tion is present and there are no other the likelihood that patients will rerisk factors (Supplementary Table Continued on following page AGA InstItItute 36 PRACTICE ECONOMICS GIHEP NEW S. COM • OCT OBE R 2014 Continued from previous page ceive the necessary genetic counseling and testing they need.9,16 The cost of dMMR/MSI testing is variable and depends on methods used (IHC and/or PCR). With the decreasing prices of germline gene panels that include not only Lynch syndrome genes but many other genes associated with hereditary cancer syndromes, it soon may be less expensive and more accurate to ofer all patients diagnosed with CRC at age 50 years or younger, and those with a personal or family history suggestive of a hereditary cancer syndrome, genetic counseling and testing. We may reserve routine tumor testing for those diagnosed with CRC at older than age 50 with no risk factors. In fact, with the cost of genome-wide analysis expected to decrease to less than $1,000 within a few years, gastroenterologists may be increasingly confronted with a patient who brings their tumor analysis, showing an alteration in MMR genes. Relevance of dMMR/MSI testing to prognosis The diagnosis of dMMR/MSI colorectal cancer has important clinical implications regarding prognosis, and has emerged as an essential component of the evaluation and management of patients with colorectal cancer, especially those with stage II colon cancer. Retrospective studies have shown that dMMR/MSI colorectal cancer is associated with a favorable prognosis independent of classic clinical prognostic factors, including stage.17,18 Patients with dMMR/MSI tumors are less likely to have lymph node and Take-away points: 1. Molecular characterization of colorectal cancer is a vital component of comprehensive oncologic care. 2. Testing for microsatellite instability (MSI) in colorectal cancer is performed in the pathology lab using immunohistochemistry and/or PCR techniques. 3. Detection of MSI colorectal cancers serves as a screening tool for identifcation of possible Lynch syndrome. 4. Patients who have MSI colorectal cancer have a better prognosis independent of stage. distant metastatic disease than patients with MMR-profcient tumors, and the prevalence of the dMMR/ MSI phenotype decreases with advancing stage at diagnosis from more than 20% in stage II to less than 4% in stage IV. In one of the largest pooled analyses of more than 7,600 colorectal cancer cases, of which 16.7% were dMMR/MSI, the hazard ratio for overall survival associated with dMMR/MSI was 0.65.17 In patients with stage II and III colon cancer, recurrence-free survival and overall survival are increased signifcantly in patients with dMMR/MSI tumors compared with those with MMR-profcient/MSS tumors.19,20 These observations, in the aggregate, support the hypothesis that dMMR/MSI tumors have reduced metastatic potential and a favorable biology compared with MMR-profcient/MSS tumors. Despite its prognostic value, MMR status is not incorporated into widely used calculators for the assessment of risk of recurrence in stage II and III colorectal cancer and does not fgure into colonoscopy surveillance recommendations after cancer resection. Nonetheless, MMR/MSI status should be assessed routinely and considered in risk assessment in all patients with stage II colon cancer because the favorable prognosis of the dMMR/MSI phenotype is a key determinant in the decision to use adjuvant chemotherapy in these patients. Although BRAF mutation confers a worse prognosis compared with BRAF wild type in dMMR/MSI colorectal cancer, the prognosis of dMMR/MSI colorectal cancer remains superior to MMR-profcient/MSS colorectal cancer, irrespective of BRAF status.5 However, BRAF status in dMMR/MSI colorectal cancer is not yet incorporated routinely into risk assessment or treatment decisions. Conclusions In a previous article in this “Practice Management: The Road Ahead” section, the authors described how gastroenterologists might develop a seamless CRC clinical service line including risk assessment for hereditary CRC syndromes.21 In addition, with rapid movement to value-based reimbursement and the potential to create a bundled colonoscopy payment methodology,22 careful consideration of how molecular testing and analysis will be incorporated into our standard CRC prevention practice will be important. Acknowledgment The authors acknowledge the help of Dr. Pei Hui for his assistance with the manuscript. Supplementary Table 1: Risk factors for Lynch syndrome ▶ CRC diagnosed at age less than 50 years ▶ Multiple CRC primaries ▶ A personal and/or family history of the following cancers: uterine, ovarian, colon-rectal, pancreatic, endometrial, gastric, ureter, renal pelvis, biliary tract, brain, small intestine, sebaceous adenoma, and/ or carcinoma, especially in families with a history of CRC ▶ Multiple family members in the same bloodline with CRC ▶ Abnormal MSI and/or IHC testing ▶ Known familial mutation for hereditary colon cancer Supplementary material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at http:// dx.doi.org/10.1016/j.cgh.2013.11.001. References 1. Markowitz, S.D., Bertagnolli, M.M. Molecular origins of cancer: molecular basis of colorectal cancer. N. Engl. J. Med. 2009;361:2449-60. 2. Al-Sohaily, S., Biankin, A., Leong, R., et al. Molecular pathways in colorectal cancer. J. Gastroenterol. Hepatol. 2012;27:142331. 37 3. Zhang, X., Li, J. Era of universal testing of microsatellite instability in colorectal cancer. World J. Gastrointest. Oncol. 2013;5:12-9. 4. Zaanan, A., Meunier, K., Sangar, F. et al. Microsatellite instability in colorectal cancer: from molecular oncogenic mechanisms to clinical implications. Cell Oncol. (Dordr). 2011;34:155-76. 5. Lochhead, P., Kuchiba, A., Imamura, Y., et al. Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication. J. Natl. Cancer Inst. 2013;105:1151-6. 6. Ward, R.L., Hicks, S., Hawkins, N.J. Population-based molecular screening for Lynch syndrome: implications for personalized medicine. J. Clin. Oncol. 2013;31:2554-62. 7. Umar, A., Boland, C.R., Terdiman, J.P., et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J. Natl. Cancer Inst. 2004;96:2618. 8. Laghi, L., Bianchi, P., Malesci, A. Diferences and evolution of the methods for the assessment of microsatellite instability. Oncogene 2008;27:6313-21. 9. Ngeow, J. Eng, C. Population-based universal screening for Lynch syndrome: ready, set ... how? J. Clin. Oncol. 2013;31:2527-9. 10. Rex, D.K., Johnson, D.A., Anderson, J.C., et al. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am. J. Gastro- Continued on following page PRACTICE ECONOMICS 38 Continued from previous page enterol. 2009;104:739-50. 11. Bao, F., Panarelli, N.C., Rennert, H., et al. Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma. Am. J. Surg. Pathol. 2010;34:1798-804. 12. Pino, M.S., Mino-Kenudson, M., Wildemore, B.M. et al. Defcient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas. J. Mol. Diagn. 2009;11:238-47. 13. Palomaki, G.E., McClain, M.R., Melillo, S., et al. EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet. Med. 2009;11:42-65. 14. Overview of testing for Lynch syn- O C TO B ER 2 0 1 4 • G I & HEPATO LO G Y NEW S drome/HNPCC. Updated 2012. Available at: http://www.nchpeg.org/index. php?option=com_docman&task=cat_view&gid=58&Itemid=. Accessed October 2013. 15. Chubak, B., Heald, B., Sharp, R.R. Informed consent to microsatellite instability and immunohistochemistry screening for Lynch syndrome. Genet. Med. 2011;13:356-60. 16. Lynch, P.M. Tumor-based screening for hereditary nonpolyposis colorectal cancer: does age-based selection optimize yield? J. Oncol. Pract. 2013;9:180-1. 17. Popat, S., Hubner, R., Houlston, R.S. Systematic review of microsatellite instability and colorectal cancer prognosis. J. Clin. Oncol. 2005;23:609-18. 18. Gryfe, R., Kim, H., Hsieh, E.T. et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N. Engl. J. Med. 2000;342:69-77. 19. Sargent, D.J., Marsoni, S., Monges, G., et al. Defective mismatch repair as a predictive marker for lack of efcacy of fuorouracil-based adjuvant therapy in colon cancer. J. Clin. Oncol. 2010;28:3219-26. 20. Sinicrope, F.A., Foster, N.R., Thibodeau, S.N., et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fuorouracil-based adjuvant therapy. J. Natl. Cancer Inst. 2011;103:863-75. 21. Braden, G.L. Allen, J.I. Organizing your clinical service line: colon cancer pre- vention. Clin. Gastroenterol. Hepatol. 2013;11:2-5. 22. Ketover, S.R. Bundled payment for colonoscopy. Clin. Gastroenterol. Hepatol. 2013;11:454-7. Dr. Gibson, Ph.D. is assistant professor of pathology, Yale School of Medicine, New Haven, Conn; Dr. Robert is professor of pathology, Yale School of Medicine; Dr. Lacy is associate professor of medicine (medical oncology), Yale School of Medicine; and Ms. Matlof, MS, CGC, is CEO of Mygenecounsel.com. [email protected] CLASSIFIEDS Also available at MedJobNetwork.com PROFESSIONAL OPPORTUNITIES Hepatologist Minneapolis/St. Paul, Minnesota PRESBYTERIAN HEALTHCARE SERVICES Albuquerque, NM Presbyterian Healthcare Services is seeking Board Certified Gastroenterology trained physicians to join our established practice of 11 physicians, 2 Gastroenterology Hospitalists and 7 midlevels. Our medical group employs more than 600 primary care and specialty providers and is the fastest growing employed physician group in New Mexico. Presbyterian Healthcare Services is a locally owned, not-for-profit organization based in Albuquerque. Our integrated healthcare system includes eight hospitals in seven New Mexico cities, a medical group, multispecialty clinics and a health plan (over 400,000 members). We have been proudly providing care to New Mexicans for 105 years. In addition to a guaranteed base salary we also offer a sign on bonus, incentive bonus, malpractice, relocation, house hunting trip, health, dental, vision, 403(b) w/ contribution from PHS 457(b), short & long term disability, CME allowance, etc. Albuquerque thrives as New Mexico's largest metropolitan center with a population of 700,000. Albuquerque has been listed as one of the best places to live in the United States by Newsweek, U.S. News & World Report, Money and Entrepreneur Magazines! Albuquerque is considered a destination city for most types of outdoor activities with 310 days of sunshine. A truly diverse and multicultural city, Albuquerque offers you and your family a great variety of activities and entertainment including national theater productions, sporting events, golf courses ranked among the best in the country, the largest hot air balloon festival in the US, American Indian Cultural activities and much more. HealthPartners Medical Group (HPMG), one of the largest multispecialty physician practices in the Upper Midwest, currently has a Hepatologist job opportunity available at Regions Hospital in St. Paul, Minnesota. We are recruiting to add a talented BC/BE Hepatologist to join our expanding GI team. You will care for our growing Hepatology patient base at our state-of-the-art Digestive Care Center within nationally recognized Regions Hospital. Fellowship training or practice experience is preferred. Join us! HPMG offers you a competitive salary and benefits package and a rewarding, patient-focused practice. Apply online at healthpartners.com or email your CV and cover letter to [email protected]. For more details, call 800-472-4695 x1. EOE For more information, e-mail Kelly Herrera at [email protected] or call 1-505-923-5662. Visit our website at www.phs.org EOE healthpartners.com Disclaimer GI & HEPATOLOGY NEWS assumes the statements made in classified advertisements are accurate, but cannot investigate the statements and assumes no responsibility or liability concerning their content. The Publisher reserves the right to decline, withdraw, or edit advertisements. Every effort will be made to avoid mistakes, but responsibility cannot be accepted for clerical or printer errors. FIND YOUR NEXT JOB AT MEDJOBNETWORK com Physician NP/PA Career Center The frst mobile job board for Physicians, NPs, and PAs Mobile Job Searches—access MedJobNetwork.com on the go from your smartphone or tablet Advanced Search Capabilities— search for jobs by specialty, job title, geographic location, employers, and more Scan this QR code to access the mobile version of MedJobNetwork.com EXCELLENT READERSHIP, QUALIFIED LEADS GI & HEPATOLOGY NEWS For Deadlines and More Information, Contact: Linda Wilson Tel: (973) 290-8243, Email: [email protected] PRACTICE ECONOMICS GIHEP NEW S. COM • OCT OBE R 2014 39 EHRs rob physicians of 4 hours of free time per week BY GREGORY TWACHTMAN Frontline Medical News U sing an electronic health records eats 48 minutes of doctors’ free time daily – or 4 hours per week – according to a survey of family physicians. At least one data management VITALS Key clinical point: Physicians may balk at using EHR systems because they consume rather than save time. Major fnding: EHR usage is accounting for 48 minutes of lost free time per day. Data source: An analysis of 411 responses to a survey. Disclosures: The study was funded by the National Library of Medicine and the American College of Physicians. The authors reported no conficts of interest. function took more time when using an EHR than when using a paper-based system, according to 411 family physicians who responded to a survey conducted by the National Functions that took longer with an EHR included returning telephone calls. Nearly 64% of respondents, all of whom were experienced EHR users, reported that �note writing took longer.’ Library of Medicine (NLM) and the American College of Physicians. The results were published Sept. 8 in JAMA Internal Medicine (2014 Sept. 8 [doi:10.1001/jamainternmed.2014.4506]). Functions that took longer with an EHR included returning telephone calls; managing messages, refll requests, or new test results; writing visit notes; ordering and scheduling tests; fnding and reviewing medical records; writing prescriptions; and reading colleagues’ notes. Nearly 64% of respondents, all of whom were experienced EHR users, reported that “note writing took longer,” according to Dr. Clement McDonald of NLM and his associates. “Surprisingly, a third (34%) reported that it took longer to fnd and review medical record data with the [EHR] than without, and a similar proportion, 32%, [reported] that it was slower to read other clinicians’ notes.” Respondents reported using a wide variety of systems, with 61 distinct EHR systems being identifed. However, nine systems were used by 20 or more respondents and accounted for 79% (324) of all users responding to the survey. Of these nine, the Veterans Afairs’ Computer Patient Record System was associated with lowest amount of free time loss at less than 20 minutes per day. “The loss of free time that our respondents reported was large and pervasive and could decrease access or increase the cost of care” Dr. McDonald wrote. “Policy makers should consider these time costs in future [EHR] mandates.” [email protected] †Over a 6-month period; P Indication: XIFAXAN® XIFAXAN® Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of C. difficile. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. There is increased systemic exposure in patients with more severe hepatic dysfunction. The clinical trials were limited to patients with MELD scores < 25. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh C). incidence than placebo in the clinical study were peripheral edema (15%), nausea (14%), dizziness (13%), fatigue (12%), and ascites (11%). Xifaxan 550 mg is licensed by Alfa Wassermann S.p.A. to Salix Pharmaceuticals, Inc. Please see brief summary on reverse. References: 1. Khungar V, Poordad F. Management of overt hepatic encephalopathy. Clin Liver Dis. 2012;16(1):73-89. 2. Xifaxan [prescribing information]. Raleigh, NC: Salix Pharmaceuticals, Inc; 2014. 3. Bajaj JS, Sanyal, AJ, Bell D, et al. Predictors of the recurrence of hepatic encephalopathy in lactulose-treated patients. Aliment Pharmacol Ther. 2010;31(9):1012-1017. Web site: www.salix.com 8510 Colonnade Center Drive, Raleigh, NC 27615 Tel. 866-669-SLXP (7597) ©2014 Salix Pharmaceuticals, Inc. All rights reserved. Printed in USA. 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