Jan 2015 by McMahon Group

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The Independent Monthly Newspaper for Gastroenterologists

Volume 66, Number 1 • January 2015

Real-World Data Mimic Trial Findings For HCV Treatment BOSTON—Drugs often fall short of the expectations set in clinical trials, because the trials often exclude patients with various comorbidities and the sickest of the sick. This does not seem to be the case with the latest generation of medications to treat hepatitis C virus (HCV) infection, which so far are meeting the high bar they set in pre-approval trials. see Real World, page 26

‘Normal’ Stomach On Endoscopy May Be Anything But Precautionary biopsies make sense PHILADELPHIA A—Nearly 30% of stomachs that appear to be normal during endoscopy in fact may have significant gastric pathology, according to a new study, which suggests that endoscopists may want to consider taking more biopsies as a precaution. see Biopsy, page 34

Falling Through the Cracks: Mothers With Hepatitis B Receive Inadequate Treatment, Follow-up

ore than on ne-third of women with the hepatitis B virus (HBV) are initially diagnoosed with the infection at their first prenatal care visit, but they do not receive follow-up care for the infection after their pregnaancy, researchers have found. The retrospective stud dy examined the medical records of 243 women with HBV who receiveed prenatal care at facilities under th he umbrella of Massachusetts Gen neral Hospital (MGH). “It’s clear from the data that these women are getting lostt to followup or not getting ap ppropriate care to begin with,” saaid Ruma Rajbhandari, MD, MPH, a gastroenterology and hepatology fellow at MGH H, in Boston, who led the sttudy. “It’s a real shame. It is siimilar to getting diagnosed with HIV and not receiving any follow-up care for it.”

The researchers presented theeir findings at the 2014 Liver Meetin ng of the American Association for th he Study of Liver Diseases (AAS SLD), in Boston (abstract 1552). In 1990, the Centers for Disease Control and Prevention created the U.S. Perinatal Hep patitis B Prevention Program (P PHBPP) in an effort too reduce perinatal trransmission of the disease. Under the PHBPP, pregnant women are rroutinely screened for HBV H and their inffants are treated an nd monitored approopriately. The prograam has resulted in a sharp reduction of p perinatal infections with HBV. see Hep B, page 32

I N S I D E

Are We There Yet? Women still feel gender disparities in pediatric gastroenterology

hen it comes to compensation, mentoring and promotions, women in pediatric gastroenterology believe they continue to lag behind their male peers, a new survey has found. see Disparities, page 22

BEST OF ACG 2014: PART 2 EXPERTS’ PICKS More of the Best of the American College of Gastroenterology annual meeting .................... page 14

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Hemorrhoids: Evaluation and Management for the Office-based Clinician ERIC FONTENOT, MD

STEPHEN W. LANDRENEAU, MD

Louisiana State University School of Medicine Department of Medicine Section of Gastroenterology New Orleans, Louisiana

The authors report no relevant financial conflicts of interest.

Hemorrhoids: Evaluation and Management for the Office-based Clinician

he medical literature on hemorrhoidal disease dates back at least as far

as Hippocrates, who described techniques that will be familiar to practitioners even today. This article will cover the epidemiology,

Internal hemorrhoidal plexus

normal anatomy and physiology, pathophysiology, and classification of

Dentate line

hemorrhoids, with a particular focus

External hemorrhoidal plexus

on the office-based physician. Epidemiology Hemorrhoids are a common problem, estimated in a large epidemiologic study to have an overall prevalence of as much as 4.4% in the United States.1 Both sexes demonstrate a peak prevalence in the age range of 45 to 65 years, with increased rates associated with higher socioeconomic status.1 However, the true prevalence of hemorrhoidal disease may be underestimated because many patients do not seek medical attention, or overestimated because some patients erroneously attribute any anorectal problem to “hemorrhoids.”2

Anatomy The anal canal (Figure 1) consists of the approximately 4 cm between the distal rectum and the anal verge. In the approximate midpoint of the canal is the dentate line, an important anatomic landmark in the

Figure 1. Normal anorectal anatomy. Courtesy of Iain Cleator MD, Vancouver, BC, Canada

evaluation and treatment of hemorrhoidal disease. The dentate line represents the junction between the embryologic endoderm and ectoderm and is the point that the mucosa of the anal canal changes from the insensitive columnar epithelium of the rectum to the highly sensitive squamous epithelium of the anoderm. Found proximally to the dentate line, the internal hemorrhoids are a specialized collection of 3 fibrovascular “cushions” arranged in a left lateral, right anterior, and right posterior configuration.3 They are composed of an arteriovenous plexus where branches of the superior, middle, and, to a lesser extent, inferior hemorrhoidal

G AST R O E N T E R O LO GY & E N D O S CO PY N E WS • JA N UA RY 2 0 1 5

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Rifaximin Redo Benefits Some With Diarrhea-Predominant IBS

pproximately two-thirds of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) who respond to an initial twoweek course of rifaximin treatment experience symptom recurrence within several months, new data show. However, clinical response can be restored in one-third of these patients by retreating them with the drug, according to the study, which was presented at the 2014 annual meeting of the American

College of Gastroenterology (abstract 45). “These long-awaited results are encouraging,” said William Chey, MD, professor of medicine and director of the GI Physiology Laboratory and codirector of the Michigan Bowel Control Program at the University of Michigan Health System, in Ann Arbor. “The finding that a significant proportion of IBS-D patients who respond to an initial course of rifaximin also respond to a second or third course provides further evidence

that rifaximin can be an effective treatment option for a subset of patients with IBS-D.” Dr. Chey, who was not involved in the study, consults for Salix Pharmaceuticals, Inc., which markets the drug as Xifaxan. Dr. Chey said the study also confirms what he and others have observed clinically: A proportion of patients who respond to rifaximin will see their symptoms recur. The researchers, led by Anthony

Lembo, MD, associate professor of medicine at Harvard Medical School, in Boston, administered rifaximin 550 mg three times daily for 14 days to 2,579 patients with IBS-D. They documented rates of clinical response, which they defined as a mean weekly decrease of at least 30% on a 10-point abdominal pain rating scale relative to baseline, along with a reduction of at least 50% in the number of days per week with loose or watery stool. Both responses had to be present during at least two of four weeks immediately following the two-week treatment. Dr. Lembo’s team that found 42% of patients (1,074 of 2,579) met the criteria for a clinical response. However, nearly two-thirds (64%) of responders had a recurrence of symptoms within 18 weeks. Nearly 640 relapsed patients received up to two additional cycles of 14 days of rifaximin (550 mg three times daily; n=328) or up to two cycles of a placebo (n=308), both in a double-blind fashion. The two-week retreatments were separated by a 10-week observation period. According to the researchers, the first retreatment led to clinical response in 33% of patients given rifaximin and 25% of those who received placebo (P=0.02). P

Retreatment seen to help about one-third of relapses. Furthermore, 37% of rifaximin recipients and 29% of placebo subjects achieved clinical response after the second cycle (P=0.04). P Dr. Lembo, a consultant for Salix, said “only a relatively small” number of patients underwent the second retreatment cycle. Still, he added, the results are particularly impressive given that any recurrent symptoms were significantly milder than the symptoms with which patients initially presented. Those milder symptoms were the baseline against which postretreatment clinical response was gauged. “Because recurrent symptoms were less severe, and therefore the new baseline scores before retreatment were lower, achieving statistical improvement may have been more difficult,” he said. Safety results were favorable, Dr. Lembo reported, with both rifaximin and placebo patients reporting similar rates of adverse events (43% and 46%, respectively). Microbial gene sequencing of some patients’ stool showed no effect of rifaximin retreatment on the intestinal microbiota or on bacterial sensitivity to antibiotics, he said. —David Wild

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Top 10 Stories of 2014 on GastroEndoNews.com 1.

Popular IBD Diet Associated With Increased Microbial Diversity January 2014

Bowel Preparation for Colonoscopy: Maximizing Efficacy, Minimizing Risk (Educational Review) October 2014

2. 3.

‘Good Vibrations’ Might Ease Constipation July 2014

Public Stool Bank Aims To Increase Safety

Landmark Crohn’s Microbiome Study Yields Important Findings

Why We Need Anesthesia Providers, Not Robots Or RNs, in GI Settings Pushing Medications

October 2014

June 2014

Fecal Transplants for IBD Show Mixed Results in Trials August 2014

November 2014

Approach to Hemorrhoids: A Primer for Gastroenterologists (Educational Review) October 2014

Candidates for Celiac Disease Detection Go Unscreened

Simple Menthol Spray 10. Can Reveal More Adenomas

July 2014

October 2014

Read these and other articles at GastroEndoNews.com. Access to online content and e-Newsletters delivered to your email inbox is FREE! Register at www.gastroendonews.com/eSignUp.aspx.

Vol. 66, No. 1 MEDICAL ADVISORY BOARD MANOOP S. BHUTANI, MD

GARY R. LICHTENSTEIN, MD

Houston, Texas

Philadelphia, Pennsylvania

ALAN F. CUTLER, MD

NIRMAL S. MANN, MD, PHD

Farmington Hills, Michigan

Sacramento, California

FREDRIC DAUM, MD

PETER R. MCNALLY, DO

Mineola, New York

Fort Carson, Colorado

STEVEN M. FABER, MD

TARUN MULLICK, MD

Elizabeth City, North Carolina

St. Charles, Illinois

RONNIE FASS, MD

JOEL E. RICHTER, MD

Cleveland, Ohio

Tampa, Florida

BARBARA B. FRANK, MD

DAVID ROBBINS, MD

Philadelphia, Pennsylvania

New York, New York

FRANK G. GRESS, MD

ELLEN J. SCHERL, MD

New York, New York

CHRISTOPHER JOLLEY, MD

PRATEEK SHARMA, MD

Gainesville, Florida

Kansas City, Kansas

MYRON LEWIS, MD

JEROME H. SIEGEL, MD

Memphis, Tennessee

New York, New York

January 2015

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GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Scratching and Sniffing the Institute of Medicine’s ‘Crisis in Cancer Care’ Report

t has been a little more than one year since the Institute of Medicine (IOM) published its observations, conclusions and recommendations for improving the quality of cancer care in America. The nearly 400-page report is titled “Delivering HighQuality Cancer Care. Charting a New Course for a System in Crisis.” As the IOM is not known for delivering kind support, kudos or compliments, this report follows true to form and leaves this physician depressed, astounded and (true to my form) a bit combative. But that will come later. The latest tome is rich with contributions from the most distinguished oncologists, scientists and government representatives. But to be honest, as a regular guy doing the daily labor of caring for patients who present with esophageal, gastric, pancreatic, hepatic, colorectal and anal cancers in a continuous flow, not much of the report is helpful and hardly rises to the level of “crisis.” Given the sum total of the IQs, clinical experience and medical-political firepower of the IOM, I elect not to joust with them regarding their choice of terminology. I’ll simply report what an old family physician told me when I—a young, high-powered, new-in-town gastroenterologist—called to say, “Dr. Metts, we have an emergency on our hands.” “Doctor,” he calmly replied, “what constitutes an emergency to you is in no way an emergency to me.” The IOM committee concluded that cancer care delivery is in crisis because of the growing demand for cancer care, increasing complexity of treatment, a shrinking workforce and rising costs. The committee became more specific as the report moved along. It concluded that too often, decisions about cancer care are not evidence-based, that many patients don’t receive palliative care and that hospice care too often is delayed. An emphasis of the report is that care should be patient-focused. The committee’s highest priority for quality care is to honor the patients’ wishes: “achieving a system that supports patient decision making is the top priority …” Really? That is not a new concept. I don’t know where all these highly respected and dedicated clinicians and scientists are spending their time; but here in “Average Town, USA,” there is no doubt that the patient is central to the care plan and that oncologists regularly spend hours of (uncompensated) time explaining to patients their treatment options. Indeed, some of the concerns of the IOM are a direct consequence of the will of the patient and the caregivers. The IOM also raised the concern that the treatments offered to patients too often do not match the findings and recommendations of the scientific community, that is, clinical trial–based care. As a practicing physician dedicated to providing trial- or evidence-based care, that application is no easy task. Applying the National Comprehensive Cancer Network’s guidelines, diagrams, footnotes and references to make informed decisions about cancer care can be more difficult and ambiguous than parsing the last line of T.S. Eliot’s poem, “The Waste Land,” which is written in Sanskrit. In many cases, patients, their families and oncologists have an insufficient number of choices of unambiguous,

The author and Sergei, a Russian wolfhound.

‘I suggest that parents and children have “the talk”—not about safe sex, checking accounts or cell phones, but about how they should approach a serious illness when it arises in their pets. Practice setting reasonable limits in the value structure, because surely as the baby boomers become ill and develop cancer, there will not be enough staff, hospitals, money, drugs or caregivers to provide everything for everybody.’ The author’s cat, Ringo.

logical, humane and sensible treatments. The dearth of options is hardly the fault of these participants. The status of care options is limited largely by a lack of effective treatments and cures for cancer in 2014. With cancer research funding being flatter than the tire on my 20-year-old racing bike, we are drifting farther away from the real issue in cancer, namely programs that cure the disease in all its forms. For the gastroenterologist taking care of the 78-year-old lady with advanced pancreatic cancer or the 65-year-old gentleman with advanced esophageal cancer, this is not a revelation. It is not difficult to keep the patient at the center of care, but it is very difficult to balance the hopes, prayers and expectations when faced with an illness for which there is no cure. The IOM confronts some of these issues in the 10 recommendations it makes to address the conclusions and meet its goals: 1. Provide patients and their families with understandable information about cancer prognosis, treatment benefits and harms, palliative care, psychosocial support and costs. 2. Provide patients with end-of-life care that meets their needs, values and preferences. 3. Ensure coordinated and comprehensive patientcentered care. 4. Ensure that all individuals caring for cancer patients have appropriate core competencies. 5. Expand the breadth of data collected in cancer research for older adults and patients with multiple comorbid conditions. 6. Expand the depth of data collected in cancer research through a common set of data elements that capture patient-reported outcomes, relevant patient characteristics and health behaviors. 7. Develop a quality health care information technology (IT) system for cancer that enables real-time analysis of data for cancer patients in a variety of care settings. 8. Develop a national quality reporting program for cancer care as part of a learning health care system. An advanced “Big Data” concept in a computer offers a calculated best-case care program based on the entire database. 9. Implement a national strategy to reduce disparities in access to cancer care for underserved populations by leveraging community interventions. 10. Improve the affordability of cancer care by leveraging existing efforts to reform payment schemes and eliminate waste. Recommendations 1 to 4 relate to the patient and his or her circle; 5 to 8 relate to IT; 9 relates to the ever-present issue of disparity; and 10 relates to cost. Recommendations 5 to 10 have been talked about for the past decade or longer. An IOM cancer report from 1999 touched on all of these items; by the institute’s own admission, not much progress has been made. Perhaps after another decade when the IT issues have been resolved, a national health care system evolves, and we have an economy that can support reasonable health care delivery, items 5 to 10 will become reality. I want to comment on items 1 to 3 because the practicing physician traverses these territories daily in caring see IOM, page 8

Q & A

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

A D V E R T I S E M E N T

Inside Vizballoons: a Q&A

What makes Vizballoons™ a unique endoscopic device?

This disposable balloon creates a small focal shield in front of the endoscopic lenses that, during the insertion phase of the procedure, creates a 100% visibility effect, and mitigates any “red-out effect.” This absolute visibility is achieved either in direct contact with the intestinal wall, acute bleeding or poor preparation situations. Observing the intestinal wall during direct contact also helps clinicians visually assess the pressure exerted by the scope onto the intestinal wall. We call this the “blanching effect,” and it is unique to our device.

perforation. Water injection temporarily disturbs visibility, as opposed to constant vision through the contained balloon. Stool and blood can dirty the water and obscure vision. Water immersion is a much slower process (injecting 1 to 2 L—and suctioning takes additional time) compared to using Vizballoons™. The red-out effect still exists with water immersion. Blanching as a measure of

the scope pressure does not exist in the water immersion, thus it will not be as safe a technique in a large number of patients.

Have there been any adverse events with the blanching such as perforations?

A. First, not many disposable devices on the market have proven to be profitable. If endoscopists know that the next patient’s procedure is going to be long and difficult, they can significantly shorten the time of the upcoming procedure by using Vizballoons™, thereby making their lab more efficient. Instead of taking extra time on a documented tortuous or difficult colon, the endoscopist can perform multiple procedures in that time. The lack of insufflation results in significantly less discomfort for the patient, which means staff do not need to manipulate, rotate or massage the patient’s abdomen.

Why is “airless and collapsed” preferable?

A. The collapsed, relaxed, nondistended lumen is the shortest possible anatomy in any patient. Thus, it is simplest to traverse, given, of course, the 100% visibility provided by Vizballoons™ enhanced by the Daisy Endo Cap™.

Q. A.

Why is Vizballoons™ better than water immersion?

With water immersion, one runs the risk that dirty water will contaminate the peritoneum in cases of even minor

With IV sedation, a clinician can become proficient within three to five cases.

Visualization Balloons, LLC 101 Eisenhower Pkwy, Suite 300, Roseland, New Jersey 07068, United States of America

A. By creating a small, transparent space

How does one justify the expense of the product?

A. None.

How does Vizballoons™ achieve its effect?

in front of the lenses, the balloon distends the collapsed lumen focally as the tip of the scope is advanced into the intestine, thus alleviating the need to insufflate air or CO2 or to inject a large quantity of water. Absence of continuous luminal distention, in turn, decreases the elongation of the lumen, as well as pain resulting from distention. A controlled clinical trial showed that insertion to the end of the lumen (cecum or small bowel) consistently takes less time with Vizballoons™ than with standard techniques.

Is there a learning curve for using Vizballoons™?

Airless Colonic Intubation: Consistently Efﬁcient with a More Comfortable Patient Experience

What makes Vizballoons™ a revolutionary breakthrough? The innovative Vizballoons™ are designed to provide the safest and most comfortable / reduced-pain solution for GI practitioners who seek to enhance their existing technology and provide superior medical results for their patients. Simple and economical to use, our revolutionary, proprietary, single-use device gives you the ability to PDQDJH \RXU HQGR VXLWH EORFN WLPH PRUH HIÀFLHQWO\ DQG with greater consistency. The result is an increase in the number of procedures per day, without any need for investments in new hardware or a lengthy learning process. For more information about the revolutionary new Vizballoons™ technology, procedures, video tutorials, product documentation and case studies, visit us online today at http://www.vizballoons.com/info-downloads/ Call: 888.507.5762 Visit: vizballoons.com

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Three years ago, it took you 30 minutes to reach a patient’s cecum, with a total procedure time of 45 minutes. Today, there’s a high probability that the same procedure will still take 45 minutes out of your block time. But until now, your choices were limited. Do you perform a costly Virtual colonoscopy—which is only used for diagnostic purposes? Do you opt for a cumbersome Double Balloon or Capsule colonoscopy? Introducing a smarter, more efﬁcient, time-saving option-- Vizballoons™. With Vizballoons™, you’ll reach the cecum in just 5 minutes and ﬁnish the entire procedure within 15 minutes… leaving you with more than enough time to schedule and perform a standard colonoscopy. Thanks to Vizballoons™, you’ll never fear those very costly and timeconsuming colonoscopies again.

See Vizballoons™ in Action! WiFi enabled tablet, scan the QR code for a direct link to the Vizballoons™ procedure video on our website.

Vizballoons™ are a disposable medical accessory, universal to all manufacturers’ endoscopes with a minimum working channel size of 3.2 mm. Vizballoons™ are shipped with ten (10) individually packaged Vizballoon catheters and ten (10) Daisy Endo Caps™ per case. Vizballoons™ offers multiple packaging options, please refer to www.vizballoons.com for further information. Vizballoons™ are intended for use in ANY situation where one seeks to avoid intestinal and abdominal distention: (a) Redundant anatomy with previous inability to reach the end of a colon; (b) Tortuous and long anatomy in cases where previous attempt took signiﬁcant time and effort.

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

IOM continued from page 6

for the cancer patient. The IOM recommends that all the participants in the cancer care continuum must reevaluate their roles in providing high-quality care. The IOM further adds that it must start with “improving the patient–clinician interaction.” From my observations over the years, several stumbling blocks that prevent a perfect union too frequently find their way into the relationship between the doctor and the patient with cancer. First, the patient or the family cannot accept that death is the likely outcome. They cannot accept that there are limits to what is reasonable or of merit in the care of a loved one dying of cancer. We are called regularly to put in feeding tubes to keep an end-stage cancer patient alive. We are asked to give chemotherapy when the data show an increase in survival of only six weeks. While the IOM states that physicians should educate all participants about the objective merits of any given treatment, it also advises that we must respect the values of the patient and the caregivers. Patient values include their expectations. This is America, and we Americans expect everything, regardless of cost. Only in recent years has the public been willing to ask the hard questions, such as “Is it worth the money to take this chemotherapy when the odds of helping are slim?” “Would I be more comfortable for my remaining time by accepting only palliative care?” and “When I decide to take radiation and chemotherapy, am I being brave or just deluded?” These are the hard questions.

The Truth About Cats and Dogs I think we, as Americans, need to practice putting limits on costs and expectations. How in the name of William Osler do we practice limiting care to a loved member of the family? It came to me last month. If you hate dogs and cats, stop reading here. My cat, Ringo, developed a bowel obstruction and I

took him to the vet. While there, he went into shock and required IV fluids, oxygen, antibiotics and digital x-rays. When he became a bit more stable, I had to decide to let him go or take him to the operating room for an exploration. I considered the cost, discomfort and odds of success. I made the difficult decision to put him to sleep.

Sergei, in repose.

I loved that cat. Five years earlier, my Russian wolfhound, Sergei, had developed a progressive hind limb neuropathy. Even after investing a lot of love, money, local and university consultations, and support, he was unable to walk. Sergei made it easy for me. One day, he told me he had had enough and his time was up. I accepted his wishes. This dog had seen me through the best of times and the worst of times. He was every bit a member of my family. Most pet owners drink the same Kool-Aid. As evidence of this acceptance of pets as family members, in 2014, Americans spent a record $58.5 billion on their pets; $15.25 billion was spent on veterinary care—Ringo and Sergei had their share. In all of this, pet insurance

will soon hit the billion-dollar mark, according to the consumer research firm Packaged Facts. I love my pets. Although I am not a fan of fish, ferrets or snakes, they too are members of someone’s family. If Americans are to change their expectations and the “cost is no object” mentality, they need to practice somewhere. Changing values is never spontaneous. Such a personal yet cultural modification requires emotional and cerebral effort in the setting of societal pressures and realities. I suggest that parents and children have “the talk”— not about safe sex, checking accounts or cell phones, but about how they should approach a serious illness when it arises in their pets. Practice setting reasonable limits in the value structure, because surely as the baby boomers become ill and develop cancer, there will not be enough staff, hospitals, money, drugs or caregivers to provide everything for everybody. If we cannot have reasonable life-value limits for our pets, how can we ever learn to have such limits for our parents, children and spouses? The IOM advises that we must respect the values and expectations of the patient; I offer that the American public must adjust their values and expectations. Part of the “crisis” is caused by attempts by all participants to maintain intense levels of care, to massage the high costs of that care, and to simultaneously attempt—at the risk of losing patient trust—to justify costs in the misplaced hope of curing what is likely incurable. What the old doctor said to me is true: A crisis to the IOM is not a crisis to me. It is time to be more reasonable, realistic, humane and honest with practice values changes. Physicians can lead the way, as always. We need to more confidently face these hard issues. Our patients will follow suit. Because I am still practicing this hard stuff of values in family matters, I hope that Sergei and Ringo understand and agree with my decisions. —Nicholas V. Costrini, MD, PhD, MBA Dr. Costrini is Director of Gastroenterology at the Nancy and JC Lewis Cancer & Research Pavilion, in Savannah, Ga.

Bariatric Surgery May Improve Kidney dney Function

n addition to helping patients shed pounds, bariatric surgery may improve their kidney function, researchers have found. Patients who are morbidly obese are at increased risk for renal failure. Although bariatric surgery is highly effective for inducing rapid weight loss, the effect of the surgery on kidney function and endstage renal disease has been unclear, said Alex R. Chang, MD, a nephrologist at the Geisinger Medical Center in Danville, Penn., who led the new study. “Our findings suggest a beneficial impact on kidney function in patients with and without baseline kidney disease,” Dr. Chang said. The researchers examined the kidney health of 3,134 patients who underwent bariatric surgery, following them for a median of 2.4 years. The mean age of the patients was 47 years. More than 36% had diabetes and more than 6% had reduced renal function.

One year after bariatric surgery, the patients’ mean weight decreased from 130.1 to 90.9 kg; mean body mass index fell from 46.8 to 32.6 kg/m2; and mean kidney function, estimated from the glomerular filtration rate (eGFR), increased from 94.8 to 99.1 mL per minute per 1.73 m2 (P<0.001). For every 5 kg of weight loss, the researchers saw an increase in eGFR of 0.50 mL per minute per 1.73 m2 in patients with chronic kidney disease who had undergone bariatric surgery over those who did not. Of the 108 patients with albuminuria—a marker of kidney dysfunction— weight loss was associated with resolution of the protein excretion in the urine (P=0.03). P The study suggests that surgery and the resulting weight loss were beneficial to the kidneys. However, more research is needed, said Dr. Chang, who noted that the current clinical standard to measure

kiidney function was creatinine, which caan be influenced by muscle mass. Rapid weight loss might reduce muscle mass and therefoore creatinine levels, but otther markers indicate th hat shedding pounds dooes benefit the kidneys. “More emphasis sh hould be placed on promoting healthy lifestyles too avoid morbid obesity an nd prevent chronic kidneey disease,” he said. Dr. Chang’s group prresented its findings at th he American Society of Nephrology’s 2014 Kidneey Week meeting. —Marie Rosenthal

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Eluxadoline Meets Phase 3 Trial End Points for IBS-D Treatment CHICAGO— —The experimental drug eluxadoline provides relief of symptoms in patients with diarrhea-predominant irritable bowel syndrome (IBS-D), according to results of two recent Phase 3 trials. Some specialists, however, were unconvinced by the data, citing a modest benefit and potentially concerning side effects. Anthony J. Lembo, MD, of Harvard Medical School’s Center for Clinical and Translational Research in Gastrointestinal Motility, in Boston, who led the studies, said, “There were significant improvements in the primary end point—simultaneous improvements in both pain and diarrhea—seen within the first few days of therapy and throughout the 26 weeks of treatment.”

Two Phase 3 Trials Pooled Eluxadoline is an oral, locally active, mixed μ-opioid receptor (µOR) agonist and delta-opioid receptor (δOR) antagonist. The drug is manufactured by Furiex Pharmaceuticals, which in April announced a sale to Forest Laboratories for an estimated $1.5 billion—a testament to the enthusiasm for new drugs to treat IBS. Forest, in turn, is being bought by Actavis, an Irish drug company, in a deal reportedly worth $25 billion. The studies (IBS3001 and IBS3002) enrolled 2,428 patients meeting Rome III criteria for IBS-D (66% women; mean age, 45 years; 20% with prior cholecystectomy; and >33% with prior loperamide use in the past year). Patients were randomized to twice-daily treatment with eluxadoline (75 or 100 mg) or placebo for 26 weeks. IBS3001 included an additional 26 weeks of double-blind treatment for long-term safety evaluations, and IBS3002 included a four-week placebo withdrawal period. In both clinical trials, the primary end point was a composite response of a daily improvement in abdominal pain of at least 30% and stool consistency evaluated over weeks 1 to 12 and weeks 1 to 26. Those intervals represented the end points for the FDA and European Medicines Agency, respectively. Additional efficacy measures included assessments of abdominal and bowel symptoms and the global end points of adequate relief, IBS-D global symptoms and quality of life.

In both trials, the most common adverse events for the 75 and 100 mg doses, respectively, were constipation (7.4% and 8.3%) and nausea (7.8% and 7.3%), compared with placebo (2.4%). About 1.3% of the patients withdrew from the study because of constipation, Dr. Lembo reported. “More than 2,500 subjects have been exposed [to the drug], with low constipation rates observed,” he said. There were eight cases of hepatobiliary sphincter of Oddi spasm. All of these patients had prior cholecystectomy, and opiate-induced sphincter of Oddi spasm is known to be associated with cholecystectomy, Dr. Lembo noted. Most patients experienced symptoms during the first week of treatment, and seven were managed as outpatients by stopping treatment. One patient was briefly hospitalized. Five patients developed pancreatitis; cases were considered mild and all these subjects had predisposing risk factors. Pancreatitis is likely due to increased contractility at the sphincter of Oddi, although the exact mechanism of action is unknown, Dr. Lembo said. The “infrequent events” of hepatobiliary sphincter of Oddi spasm and mild pancreatitis improved rapidly and without sequelae, he said, adding that risks may be mitigated through education and appropriate patient selection.

Statistical Versus Clinical Meaning Dr. Lembo, who presented the findings at Digestive Disease Week 2014 (abstract 929d), was peppered with questions from the audience. One listener argued that “the drug has, at best, extremely modest effects, with about 10% improvement over placebo, which is statistically significant primarily because of the number of patients in the study.”

Dr. Lembo reported serving on advisory committees or review panels for AstraZeneca, Forest Research Institute and Salix Pharmaceuticals, and consulting for Ironwood Pharmaceuticals and Prometheus Laboratories. Dr. McCallum disclosed financial relationships with, research support from or participation in advisory panels and review committees of Forest Laboratories, Ironwood Pharmaceuticals, Medtronic, Novartis Pharmaceuticals, Prostrakan Pharmaceuticals, RedHill Biopharma, Rhythm Pharmaceuticals and Salix Pharmaceuticals.

Table. Primary Composite End Point in Pooled Trials of Eluxadoline Men

Drug Effectiveness Observed Eluxadoline met the primary end point of the composite response, for both doses and in both studies (assessed at weeks 12 and 26). “Efficacy was observed in both males and females, and was demonstrated for patients’ most bothersome IBS-D symptoms of diarrhea, urgency/frequency and pain,” Dr. Lembo said (Table). For the individual components of the end point, differences were statistically significant at both time points for stool consistency, showing an approximately 12% difference favoring eluxadoline (P<0.001). For pain response the difference was 4%, which was not significant at 12 or 26 weeks. Results were more robust for the 100 mg dose of eluxadoline in the prespecified secondary end points of improvement in pain by at least 40% and by 50% or greater, Dr. Lembo said: a 6% improvement (P=0.003) P and a 7% improvement (P=0.011) P compared with placebo, respectively. Patients who received eluxadoline at both doses also had greater improvements in number of daily bowel movements and urgent episodes, daily IBS-D global symptom scores and IBS-Quality of Life scores (P<0.05).

Dr. Lembo acknowledged that the efficacy was somewhat modest, but he pointed out that “the 10% [change] over placebo is not dissimilar to other drugs in this class.” Others were concerned about side effects, particularly five cases of pancreatitis that could have been related to the drug. Dr. Lembo responded, “We presented sequelae of sphincter of Oddi spasm and pancreatitis that may be concerning, even though the events were relatively mild in this study. There does seem to be a group of patients particularly at risk, especially those with prior cholecystectomy and other issues with the pancreas, such as chronic alcohol use.” Richard McCallum, MD, professor and founding chair of the Department of Medicine at Texas Tech University Health Sciences Center, in El Paso, said the effects of the drug on symptoms appeared to be statistically significant but not clinically meaningful. What’s more, he said, “gas and bloating are important symptoms in IBS, and they are often not well defined in the global symptom score analysis. It is very important to understand if these symptoms were reduced, compared to placebo results.” The study did not provide that analysis. —Caroline Helwick

Weeks 1-26

Women

Eluxadoline, 100 mg (N=268)

Placebo (N=282)

P Value

Eluxadoline, 100 mg (N=538)

Placebo (N=527)

P Value

26.10%

15.20%

0.002

27.50%

17.50%

<0.001

31.70%

19.10%

<0.001

30.70%

19.70%

<0.001

ONE HE’S BEEN WAITING FOR IS HERE

One tablet contains ledipasvir and sofosbuvir

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Armamentarium of Novel Diabetes Drugs Expanding AUSTIN, TEXAS—An unprecedented growth in treatment options for type 2 diabetes mellitus (DM) means more patients can achieve disease control, experts told attendees of the 2014 annual meeting of the American College of Clinical Pharmacy (ACCP).

PharmD, clinical assistant professor in the Department of Pharmacy Practice, University of Mississippi School of Pharmacy, in Oxford. He pointed to data showing that the recently approved SGLT2 inhibitor, empagliflozin (Jardiance; Boehringer Ingelheim), which

Glucose in the bloodstream Gluc cose passing through the kidn ney of a patient with type 2 diab betes on an SGLT2 inhibitor

‘A high-glucose environment is something that bacteria can thrive in; hence the increased risk for infection.’ —Matthew Strum, PharmD

Many patients have enthusiastically embraced the efficacy, convenience and added weight loss associated with sodium glucose co-transporter 2 (SGLT2) inhibitors and glucose-like peptide 1 receptor agonists (GLP-1 RAs), according to R. Keith Campbell, PharmD, CDE, Distinguished Professor in Diabetes Care and Pharmacotherapy at Washington State University College of Pharmacy, in Pullman. “The more patients use these agents, the more they like them,” said Dr. Campbell, who did not take part in the ACCP presentations.

New Oral Agents: SGLT2 Inhibitors Because they can be used as monotherapy or as add-ons to other oral agents, SGLT2 inhibitors have proven versatile, said Matthew Strum,

joins canagliflozin (Invokana, Janssen) and dapagliflozin (Farxiga, BristolMyers Squibb), is most effective in combination with metformin. The data are from an open-label, 78-week extension study that compared empagliflozin (10 or 25 mg) with sitagliptin (Januvia, Merck), metformin alone, or metformin combined with one of these two agents (Diabetes Care 2013;36:4015-4021). The results showed that after 78 weeks of treatment, empagliflozin 25 mg in combination with metformin led to a mean 0.77% reduction in hemoglobin A1c (HbA1c) and a mean 32 mg/ dL reduction in fasting plasma glucose. In contrast, sitagliptin with metformin was associated with a mean 0.13% reduction in HbA1c and a decrease of 16 mg/dL in fasting plasma glucose.

Increased loss of glucose through the urinary tract

New Study Shows Gastric Stimulation Effective For Refractory Gastroparesis, Best for Diabetics

lectrical stimulation for refractory gastroparesis yields mixed results, with some symptoms responding better to the therapy than others and patients with diabetes experiencing particularly high rates of success, new research shows. A prospective case series of nearly 140 patients undergoing gastric electrical stimulation (GES) for gastroparesis found that 75% reported improvements in appetite, nausea and vomiting, but other symptoms were less likely to improve. Individuals with diabetes and gastroparesis experienced the best results, although why that was the case is unclear, according to the researchers, who presented the findings at the 2014 annual meeting of the American College of Gastroenterology (abstract 67). “These results are impressive and show GES is effective in a large group of patients with very refractory gastroparesis,” said Kenneth Koch, MD, professor of internal medicine and chief of gastroenterology at Wake Forest University Baptist Medical Center, in

Winston-Salem, N.C. Dr. Koch was not involved in the research. To fine-tune how the efficacy and safety of GES is understood, senior investigator Henry Parkman, MD, professor of medicine and head of the Gastrointestinal Motility Laboratory in the Department of Medicine at Temple University, in Philadelphia, and his colleagues examined 151 patients with refractory gastroparesis who had a GES device (Enterra; Medtronic, Inc.) implanted between July 2010 and November 2013. The patients had not responded to prior treatments with prokinetic agents such as metoclopramide or domperidone, or to antiemetic agents such as compazine and ondansetron. Approximately half of the patients had diabetes, and the rest had idiopathic gastroparesis. The patients, 120 of whom were women, were a mean age of 38.2 years at the time of implantation. To document post-implantation response, the researchers asked patients to complete the Clinical

Patient Grading Assessment Scale (CPGAS) at each follow-up visit. A seven-point increase in CPGAS scores indicates complete improvement and a sevenpoint decrease indicates symptoms have become “very much worse.” Two patients with diabetes required removal of the GES after developing infection around the device; one patient with diabetes died before follow-up; and 10 patients did not return for follow-up. Among the 138 remaining individuals, who were seen a mean 520 days (±350 days) following GES implantation, 75% (104 of 138) reported that their symptoms had improved, including 43% (60 of 138) who reported marked improvements. The remaining 25% (34 of 138) said their symptoms did not change or had gotten worse. When Dr. Parkman’s team looked at specific symptoms, they found the greatest improvements occurred in appetite (average 34% improvement), nausea (30%),

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Weight Loss Advantage The combination of empagliflozin 25 mg with metformin also led to reductions in systolic blood pressure (mean 3 mm Hg) and significant weight loss (mean 2.5 kg), Dr. Strum noted. “The weight reduction we’ve seen with both SGLT2 inhibitors and GLP-1 RAs gives them a significant advantage over other agents,” he said. CANTATA-SU, a randomized, double-blind, Phase III trial, included 1,450 patients with type 2 DM, who received metformin with once-daily canagliflozin 100 or 300 mg, or with glimepiride, a long-acting sulfonylurea antidiabetic drug (Lancet 2013;382:941-950). After 52 weeks of treatment, 300 mg of canagliflozin

a mean 0.81% reduction in HbA1c and a mean 18 mg/dL decrease in fasting plasma glucose. “One striking finding from a study of dapaglifozin as an add-on to pioglitazone was that dapagliflozin mitigated the weight increases that occur with pioglitazone monotherapy,” said Dr. Strum, pointing to findings showing a mean 1.3-kg increase in weight in patients receiving 10 mg of dapaglifozin with at least 30 mg of pioglitazone daily, versus a mean 3 kg rise in weight in patients who took pioglitazone alone (Diabetes Care 2012;35:1473-1478). The greatest reductions in both HbA1c and fasting plasma glucose also occurred with a combination of the two agents, Dr. Strum said.

‘Although gastrointestinal adverse events with GLP-1 RAs are not uncommon, they are generally transient and do not require treatment discontinuation.’ —Krystal Edwards, PharmD

with metformin led to a mean 4 kg reduction in weight, compared with a mean 0.7 kg weight increase in the glimepiride with metformin group, Dr. Strum said. Subjects receiving the combination therapy also experienced a mean 0.93% reduction in HbA1c and a mean 27 mg/dL decrease in fasting plasma glucose. In contrast, subjects administered glimepiride with metformin experienced

SGLT2 and Risk For Genitourinary Infections A caveat to these positive findings is a risk for genital and urinary tract infections that accompanies all of the SGLT2 inhibitors, Dr. Strum noted. “The most common reason my patients have had to discontinue these agents is because they’ve developed a urinary tract infection, or in women, vulvovaginitis, or in

uncircumcised men, balanitis [swelling of the head of the penis],” he said. The mechanism of action? “You are putting more glucose in the urine as a result of using these medications,” he explained. “A high-glucose environment is something that bacteria can thrive in; hence the increased risk for infection.”

GLP-1 Receptor Agonists Two recent additions to the GLP-1 RA class of drugs, albiglutide (Tanzeum, GlaxoSmithKline) and exenatide synthetic (Bydureon, AstraZeneca), have the added convenience of once-weekly administration, said Krystal Edwards, PharmD, associate professor at Texas Tech University Health Sciences Center’s School of Pharmacy, in Dallas/Fort Worth. “There are also strong efficacy data supporting their use,” said Dr. Edwards, who spoke at the same ACCP session. Such evidence is documented in the randomized, open-label DURATION-3 trial, which compared 2 mg of exenatide synthetic once weekly to glargine in 456 patients with type 2 DM who had not achieved adequate glycemic control with at least three months of treatment with oral glucose-lowering drugs at the maximum tolerated doses. Exenatide synthetic was found to effectively control hyperglycemia (Lancet Diabetes Endocrinol 2014;2:464-473). Some patients continued treatment with metformin or combined metformin and sulfonylurea during the trial. After three years of treatment, the researchers found that HbA1c levels decreased by a mean 1.01% in patients receiving exenatide synthetic with or

‘I would be less likely to implant the device in patients with idiopathic gastroparesis.’ —Henry Parkman, MD retching (27%) and upper abdominal pain (26%). Symptoms that did not improve as much included postprandial fullness (21%), constipation (17%) and abdominal distension (11%). Although these are not the first set of findings showing variability in response of specific symptoms, the reason behind this uneven effect remains unclear, Dr. Parkman said. “One theory is that GES has differing effects on the

afferent sensory and efferent motor neural pathways, and some symptoms of gastroparesis are mediated by one pathway, whereas others are mediated by the other— hence the range in symptom response,” he said. Dr. Parkman’s team also found variability in response among patients with idiopathic or diabetic gastroparesis, with the group with diabetes reporting greater overall improvements on the CPGAS (1.5±0.5 vs. 3.5±0.3 increase in scores, respectively).

without the other oral agents, compared with a mean 0.81% reduction in those administered glargine, with or without the oral agents (P=0.03). Notably, rates of hypoglycemia were three times lower in patients treated with exenatide than in those given the other drug regimens (0.3 episodes per patient-year vs. 0.9 episodes with exenatide vs. glargine, respectively). In contrast, safety data were less favorable: More exenatide synthetic recipients experienced gastrointestinal adverse events, including nausea (15% vs. 2% for exenatide synthetic vs. glargine, respectively), vomiting (6% vs. 3%) and diarrhea (14% vs. 7%). “Although gastrointestinal adverse events with GLP-1 RAs are not uncommon, they are generally transient and do not require treatment discontinuation,” Dr. Edwards said. Similar to the SGLT2 inhibitors, GLP-1 RAs are associated with weight loss, Dr. Edwards said, pointing to research demonstrating reductions of 1.5 to 4 kg after six to 18 months of type 2 DM treatment with exenatide or liraglutide (Diabetes Obes Metab 2014;16:921). In a trial of liraglutide in obese individuals, 64% of patients lost at least 5% of their body weight after a year of treatment with 2.4 or 3 mg of liraglutide (Int J Obes [Lond] 2012;36:843-854).

FDA Acts on Positive Data Results like these were impressive enough to prompt an FDA advisory panel to recommend approval of liraglutide for use as a treatment for obesity. see Novel Diabetes, page 21

“This association is also not clear, but it could be that the mechanism of gastric emptying in diabetic gastroparesis is different than the mechanism in idiopathic gastroparesis,” he said. Dr. Parkman said the research should help guide clinicians in selecting patients most likely to respond to GES treatment. “I would be less likely to implant the device in patients with idiopathic gastroparesis,” he said. Other options for these patients include pyloromyotomy and domperidone, which requires investigational drug approval from the FDA, he added. Dr. Koch said one notable finding of the study was that 43% of responders and 41% of nonresponders used narcotics. “Although narcotics can cause nausea and slow gastric emptying, in this review GES was equally effective,” Dr. Koch said, adding the findings need to be validated in further research. —David Wild Drs. Parkman and Koch reported no relevant financial conflicts of interest.

ACG 2014

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Best of ACG 2014: Part 2 Gastroenterology & Endoscopy News asked three experts on inflammatory bowel disease to comment on several abstracts presented at the 2014 annual meeting of the American College of Gastroenterology that they believe are clinically significant and applicable. Gary Lichtenstein, MD Professor of Medicine and Director of the Center for Inflammatory Bowel Disease at the Raymond and Ruth Perelman School of Medicine, of the University of Pennsylvania, in Philadelphia

Predictors of Hospitalization in Patients with Moderately to Severely Active Ulcerative Colitis From ULTRA 1 and ULTRA 2 (Feagan B, et al) Most of the cost of caring for patients with inflammatory bowel disease (IBD) is accounted for by surgery and hospitalization, in addition to medication. Because disease deterioration is a frequent reason for hospitalization, if we can identify a treatment approach that prevents disease deterioration, we may be able to also reduce the risk for hospitalization.

P1050.

Key predictors of hospitalization were a high baseline CRP (precise definition depends on assay used; OR, 1.01-1.02) and an albumin less than 40 g/L (OR, 2.39-2.82) We know from prior data that infliximab treatment is associated with a reduced rate of hospitalization (Costa J, et al. Inflamm Bowel Dis 2013;19:20982110). This study is very important, because it helps discern additional factors that predict hospitalization, specifically in patients with ulcerative colitis (UC), who took part in the ULTRA 1 and ULTRA 2 studies of adalimumab (Humira, AbbVie) but received a placebo during the first placebo-controlled phases of the two studies. The results identified several factors associated with hospitalization among patients who did not receive adalimumab at first. The most significant factors were male gender, increased inflammation as measured by C-reactive protein (CRP), and low baseline serum albumin levels.

The predictive value of low baseline serum albumin is a particularly interesting finding. Low baseline serum albumin fin has also been identified as a predictor of nonresponse to anti-TNF (tumor necrosis factor) therapy. In nonresponse to anti-TNF agents, it is thought that more active and severe UC is associated with protein loss through the colon. As a consequence of this loss, both albumin and the administered biologic drug are lost in the stool. So, because the drug is lost in the stool, individuals do not receive adequate amounts of the medication and therefore are less likely to respond to treatment. Measuring CRP and albumin may be important in relation to future outcomes in individual patients who have failed conventional therapy. We might eventually include CRP and serum albumin, and other similar factors, in “prognostigrams” to help us stratify the risk for hospitalization and surgery. It would be interesting to examine what happens to albumin levels in response to particular agents, and to try and correlate the administered drug’s efficacy with those levels as well as with the risk for hospitalization and surgery. Although we’re not quite there yet, this study is part of a line of research that will help us identify the overall risk for hospitalization and surgery for an individual patient, and to ultimately help us determine our treatment strategies.

Information was derived from claims in the Medicare database between 2006 and 2010, including white IBD patients with NMSC who underwent surgical excision within 60 days of diagnosis. Analyses classified patients according to use of thiopurines, anti-TNF agents or both, before and after NMSC treatment. Patients with known risk factors for NMSC, including HIV, organ transplant, xeroderma pigmentosa, albinism and use of other immunosuppressants, were excluded.

The Risk of a Second Non-Melanoma Skin Cancer with Thiopurine and AntiTNF Use in Inflammatory Bowel Disease (Scott FI, et al)

Despite the lack of statistical significance, I don’t think we can exclude the possibility that a second NMSC is related to thiopurine use. At the same time, there is not enough evidence

A63.

Longitudinally studying the risk for and incidence of skin cancers in patients with IBD is important for several reasons: Individuals with IBD inherently have a higher risk for melanoma (Singh S, et al. Clin Gastroenterol Hepatol 2014;12:210-218), and the use of thiopurine is associated with an increased risk for non-melanoma skin cancer (NMSC)—a risk that persists even after stopping the drug. (Biologics have been associated with a higher risk for melanoma, but not with NMSC.) The question that this cohort study addressed was how the use of an antiTNF agent or thiopurine affected the risk for developing a second NMSC among patients who already had one diagnosed and excised.

Table. With Thiopurine and Use of Anti-Tumor Necrosis Factor Treatment

Adjusted Hazard Ratio (95% confidence interval)

Anti-TNF vs. thiopurine, pooled analysis

0.80 (0.35-1.81)

Anti-TNF vs. thiopurine with no thiopurine prior to surgery

0.30 (0.05-1.93)

Anti-TNF vs. thiopurine with thiopurine prior to surgery

1.48 (0.47-4.61)

Combination therapy vs. anti-TNF monotherapy

0.85 (0.28-2.56)

Duration analyses • Short-term continued anti-TNF use (<1 y)

1.15 (0.52–2.54)

• Long-term continued anti-TNF use (>1 y)

0.91 (0.48–1.75)

• Recently discontinued anti-TNF use

1.04 (0.37-2.93)

• Short-term continued thiopurine use (<1 y)

1.68 (0.94-3.00)

• Long-term continued thiopurine use (>1 y)

1.39 (0.88-2.20)

• Recently discontinued thiopurine use

0.57 (0.20-1.59)

to definitively say there is an association. Patients were also classified by the duration of exposure to these agents, both before and after NMSC treatment. Analyses also adjusted for known risk factors such as age, sex, latitude, nursing home residence, certain comorbidities, corticosteroid use, keratosis and the number of dermatology visits. Only residence in median latitudes predicted a second NMSC. In terms of treatment type, exposure to anti-TNFs did not increase the risk for a second NMSC, which makes sense given that it also does not increase the risk for a first NMSC (Table). More surprising, however, was that the risk for a second NMSC was twoto threefold greater with the use of thiopurine, regardless of the treatment

duration, but this was not statistically significant. The concern here is that, even with the large population of patients included in this analysis with observation for a substantial length of time, it is difficult to demonstrate a statistically significant correlation between thiopurine use and a second NMSC. It seems that what is needed is an even higher number of patients in order to determine the statistical significance of the risk. Despite the lack of statistical significance, I don’t think we can exclude the possibility that a second NMSC is related to thiopurine use. At the same time, there is not enough evidence to definitively say there is an association. see BoACG, page 16

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ACG 2014

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

BoACG continued from page 14

Regardless of the statistical significance, a threefold increased risk is not very high, and it should give us comfort in telling our patients that even if they have had an NMSC previously, we can still consider using these agents, assuming they take precautionary measures against sun exposure and undergo frequent skin examinations by a physician. Given the risk for melanoma in

general in IBD patients, regardless of their medication use, I also encourage my patients to protect themselves from the sun, and preferably not to go into the sunlight at all. If they do, I advise them to be followed closely by a dermatologist. Anti-TNF Agents Prevent Endoscopic and Clinical Recurrence of Crohn’s Disease After Surgical Resection: A Meta-Analysis (Mardini EH, et al)

P1040.

In 1990, Paul Rutgeerts, MD, presented data showing that more than 70% of Crohn’s disease (CD) patients treated surgically with ileocecal resection will develop endoscopic recurrence within one year of surgery (Rutgeerts P, et al. Gastroenterology 1990;99:956-963). He also developed the Rutgeerts scoring system, a grading approach that stratifies patients’ risk for clinical recurrence based on their endoscopic recurrence within a six- to 12-month time frame. More severe endoscopic recurrence during that period is likely to be followed by clinical

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recurrence within seven to eight years, according to Dr. Rutgeerts. Given the association between early endoscopic recurrence and subsequent clinical recurrence, reducing the risk for endoscopic recurrence postoperatively is an important treatment goal. Previously, Miguel Regueiro, MD, showed, through a small single-center study, that antiTNF agents can achieve a significant reduction in postoperative endoscopic and clinical recurrence (Regueiro M, et al. Gastroenterology 2009;136:441-450). However, that study’s small population limited its strength. This current meta-analysis included 127 CD patients from four randomized trials that compared 53 patients treated with infliximab (Remicade, Janssen Biotech) or adalimumab with 74 controls administered azathioprine and/or 5-aminosalicylic acid (5-ASA).

‘Given the association between early endoscopic recurrence and subsequent clinical recurrence, reducing the risk for endoscopic recurrence postoperatively is an important treatment goal.’ —Gary Lichtenstein, MD

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Pooled risk ratio analyses demonstrated a significant reduction in the likelihood of endoscopic as well as clinical recurrence in patients who received anti-TNF agents (risk ratio [RR] for endoscopic recurrence, 0.179; 95% confidence interval [CI], 0.084-0.383; P≤ P 0.001, and RR for clinical recurrence, 0.374; 95% CI, 0.172-0.784; P=0.013). P Although the study demonstrates a clear benefit in reducing endoscopic and clinical recurrence after surgical resection, particularly compared with the traditional agents azathioprine and 5-ASA, the issue remains that this metaanalysis also included small sample sizes. One would hope that this limitation will be overcome by a trial that is in progress and that will include a large cohort of individuals (NCT identifier: 01190839). The multicenter study involves 175 sites and compares CD patients receiving either infliximab or placebo for prevention of postoperative recurrence. With the significant number of patients enrolled, the trial should be adequately powered to provide definitive information on whether infliximab can be used as a preventive agent to keep patients from developing recurrence postoperatively. This study will likely be presented at Digestive Disease Week later this year.

ACG 2014

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Peter Higgins, MD Director of the Inflammatory Bowel Disease Program at the University of Michigan, in Ann Arbor

Vedolizumab Induces Clinical Response and Remission Across a Range of Baseline Fecal Calprotectin Levels in Patients with Ulcerative Colitis: Results from GEMINI 1 (Wyant T, et al) One might think that because vedolizumab (Entyvio, Millennium Pharmaceuticals) is a slow-acting drug, it might take much longer to bring patients with more severe inflammation under control, or that it could even be less successful in inducing response in such patients. That question hasn’t been addressed until now. In this study, patients with UC who had participated in GEMINI 1 were stratified according to the amount of inflammation they had at study outset, which was measured using fecal calprotectin. The investigators looked at two categories of patients: those with less than 250 mg/L of fecal calprotectin, which is considered histologic inflammation that can only be seen under the microscope, and those with more than 500 mg/L of fecal calprotectin, which reflects a relatively high level of inflammation.

P442.

So, although the success rate of vedolizumab seems to be slightly lower if patients have more severe disease, the efficacy relative to placebo was nearly the same. I think the message from this study is that one should not worry that vedolizumab won’t work in our very sick UC patients as well as it does in less affected patients. Both sets of patients derive a significant benefit from the drug. The question this study did not address is whether it takes longer to turn our very sick patients around. Although clinical

experience suggests that is the case, I think we need strong prospective data to determine that conclusively.

Activity Index (CDAI) had been the standard measure for clinical outcomes in trials of Crohn’s disease treatments. Recently, however, the FDA ruled against using it in clinical trials going forward, citing the CDAI’s complexity, high placebo response rate and inconsistency with the agency’s guidance on patientreported outcome measures. What these current researchers wanted to find out is if any elements from the CDAI could be salvaged and used as a way of determining clinical

Evaluation of an Interim Crohn’s Disease Outcome Measure (PRO−2) Based on 2 Patient-Reported Components (Stool Frequency, Abdominal Pain) of the Crohn’s Disease Activity Index (CDAI) in the Ustekinumab CERTIFI Study Gasink C, et al) Until recently, the Crohn’s Disease

P445.

see BoACG, page 18

‘One should not worry that vedolizumab won’t work in our very sick UC patients ... [They] derive a significant benefit from the drug.’ —Peter Higgins, MD

The findings showed that response rates were only slightly lower with vedolizumab in patients with more inflammation, and that the differences in response rates between placebo and vedolizumab were similar for patients with mild inflammation and with severe inflammation. Specifically, 54% of patients with mild inflammation experienced a clinical response with vedolizumab compared with 30% with placebo, and 48% of patients with severe inflammation experienced a clinical response with vedolizumab compared with 25% with placebo.

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ACG 2014

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

BoACG continued from page 17

outcomes, including how patients are feeling and functioning. They isolated two CDAI questions, one regarding stool frequency and the other regarding abdominal pain, and analyzed how they correlated with CDAI responses provided by subjects in the CERTIFI study of ustekinumab (Stelara, Janssen Biotech).

‘What we need is an objective marker of inflammation that reduces the likelihood of missing those individuals with asymptomatic inflammation.’ —Peter Higgins, MD

The study found that the two questions correlated reasonably well with the full CDAI criteria for disease remission and disease activity, yielding a sensitivity of 85% and a specificity of 74% in identifying patients with remission or active disease as defined by CDAI scores. The results are important from research and clinical perspectives: Patient-reported outcomes are one of two end points that the FDA wants CD studies to document, along with objective evidence of reduced inflammation, when anti-inflammatory drugs are being studied. So, having an instrument like this is critical if we do not want our CD clinical trials to slow down significantly or even to stop. From a clinical standpoint, the results suggest we can obtain a quick snapshot of how our CD patients are doing simply by asking them two questions: “How many liquid or soft stools are you having per day?” and “How much abdominal pain are you having?” The answers can then guide us and help us determine whether we should be performing more tests to understand the extent of inflammation and disease activity. It should be noted that although the two questions may give us a sense of a patient’s level of disease activity, about 10% to 20% of all CD patients have active inflammation but not much in the way of symptoms. So, what we need is an objective marker of inflammation that reduces the likelihood of missing those individuals with asymptomatic inflammation. Ideally, a low-cost screening test like CRP or fecal calprotectin could be used to screen for inflammation in patients with few

symptoms, but some patients produce very little CRP, and fecal calprotectin remains an expensive test in the United States. C-Reactive Protein and Erythrocyte Sedimentation Rate Do Not Correlate With Disease Activity in Pregnant Women With IBD (Leung Y, et al) Most of us know that erythrocyte sedimentation rate (ESR) increases during pregnancy and therefore it cannot be reliably used as a marker of diseaserelated inflammation in pregnant IBD patients. What many of us have been doing instead is measuring a different serum biomarker, CRP, to get a sense of the extent of disease-related inflammation in these pregnant patients. With that in mind, for those of us who use CRP in this population, the results from this study are very disappointing. The researchers found that neither CRP nor ESR proved to be accurate measures and predictors of disease activity during pregnancy. It seems that the changes that take place during pregnancy, including shifts in blood volumes and blood proteins, affect the reliability of both of these measures as inflammatory markers. Both ESR and CRP gradually rise throughout pregnancy, and do not reliably differentiate active from inactive mild to moderate disease.

to perform an endoscopy and be sure. Future studies may confirm that fecal calprotectin can be a useful screening test in pregnancy.

P1082.

‘If you have a suspicion that a pregnant patient may be experiencing an IBD flare, the right thing to do is to perform an endoscopy and be sure.’ —Peter Higgins, MD

The one biomarker that might still be helpful but was not studied here is fecal calprotectin. The reason it might be helpful is that it originates from neutrophils in the intestinal mucosa, and therefore may be protected against the changes that take place during pregnancy, which would make it a candidate for a reliable biomarker of disease activity. However, that requires further study. At this point, I think what we can say is that if you have a suspicion that a pregnant patient may be experiencing an IBD flare, the right thing to do is

Rajiv Chhabra, MD Assistant Professor of Medicine at the University of Missouri Kansas City School of Medicine, and consultant gastroenterologist at Saint Luke’s Hospital, in Kansas City, Kansas

Overt Obscure GI Bleed: What Do We Miss on Colonoscopy? Analysis of a Large Database (Linares CRS, et al)

P1398.

Current guidelines of the American Society for Gastrointestinal Endoscopy (ASGE) recommend repeating esophagogastroduodenoscopyy or colonoscopy in patients with gastrointestinal bleeding with an unidentified cause after initial colonoscopy (Gastrointest Endosc 2010;72:471-479). If a cause remains unidentified after a second procedure, the guidelines recommend small bowel evaluation using video capsule as well as deep enteroscopy. This study set out to document the ability of repeat colonoscopy to detect culprit lesions in patients with overt obscure gastrointestinal bleeding. Although one systematic review found about 20% of adenomatous polyps are missed during initial colonoscopy ((Am J Gastroenteroll 2006;101:343-350), there is little data on other types of missed lesions, and it is thought the detective yield of a repeat colonoscopy is limited, particularly when the initial colonoscopy was complete and bowel preparation was adequate. With that context in mind, I think this retrospective study was very interesting; it showed that in patients requiring a second procedure for overt obscure GI bleeding, 50% of culprit lesions detected with double-balloon enteroscopy using a retrograde approach were within reach of a colonoscope, suggesting that perhaps a repeat colonoscopy should be added to the diagnostic algorithm in these patients. The study has important limitations: It was retrospective, and it did not report any

data on the quality and completeness of the initial colonoscopy in these patients. It also did not indicate whether a capsule study was performed in these patients prior to double-balloon enteroscopy. If a capsule study was conducted, it might have affected the diagnostic yield of double-balloon enteroscopy, as a study showed (Gastrointest Endosc 200 2008;68:98-104). Despite these limitations, the study is important, and it highlights the population in whom lesions are missed because either the patient is not actively bleeding at the time of initial colonoscopy or the lesion is located behind the folds of the intestine. With these findings in mind, and pending further prospective studies and a change in ASGE guidelines, the data suggest clinicians should try and identify a culprit lesion using repeat colonoscopy in patients with obscure gastrointestinal bleeding before proceeding with a more lengthy and complex deep enteroscopy. Nonselective β-Blockers May Negatively Impact Survival in Patients with Decompensated Cirrhosis (Confer B, et al) More than 500 studies have been published on the use of non-selective β-blockers (NSBBs) in the management of cirrhosis. Although data have generally favored a role for NSBBs in treating cirrhosis, the advantage of using NSBBs must be weighed against the risks associated with their long-term use, including reductions in cardiac output that can lead to decreased renal perfusion and hepatorenal syndrome. One way to improve the risk–benefit ratio of these agents is to administer β-blockers only in patients at substantial risk for bleeding, including those with medium or large varices or patients with small esophageal varices who have Child-Pugh class C cirrhosis. Measuring hepatic venous pressure gradient (HVPG) before and one to two months after NSBB administration also helps identify responders who are most likely to benefit from continued NSBB prophylaxis. Responders are patients with an HVPG less than 12 mm Hg one to two months after initiation of treatment, or those who have a decrease of more than 20% in HVPG compared with their pretreatment value. Patients who do not respond to treatment so quickly have only a small chance of deriving therapeutic benefits, and therefore should discontinue therapy to avoid side effects.

P864.

see BoACG, page 20

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ACG 2014

BoACG continued from page 18

In a further effort to improve the risk–benefit profile of using NSBBs, this study examined a segment of cirrhotic patients that has been excluded from almost all randomized controlled trials comparing NSBBs with placebo or other pharmacotherapy: those with advanced decompensated cirrhosis. In this population of patients, the study found that NSBB use is associated with a 2.3-fold increase in the risk for death

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

within five years, compared with patients not administered NSBBs. The major limitation of the study is that it was not a randomized controlled trial, but instead a historical cohort study. In addition, HVPG was not measured at baseline and after one to two months to identify nonresponders, leaving the possibility that they excluded nonresponders and thereby potentially reduced the mortality rate. Since the researchers also did not specify the cause of death, it is plausible that a significant

number of deaths occurred due to hepatocellular carcinoma, which makes it difficult to assign direct causality to NSBB as a cause of death. Despite these limitations, the study raises an important question concerning the safety of NSBB use in patients with decompensated cirrhosis. The risk– benefit ratio of such treatments may vary according to the stage of cirrhosis, and NSBBs may be an unfavorable choice in patients with the most advanced stage of the illness.

Serum Ceruloplasmin, Ferritin, and Their Ratio Are Significantly Associated With Nonalcoholic Steatohepatitis in Patients With NAFLD (Issa D, et al)

29.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease. According to available data, NAFLD affects more than 20% of people in the United States and its prevalence is increasing. NAFLD encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Because approximately 20% of those who develop NASH also will develop cirrhosis, making a NASH diagnosis before patients become cirrhotic can have important implications for treatment, including the decision to more aggressively treat metabolic risk factors for cirrhosis.

‘Because approximately 20%

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of those who develop NASH also will develop cirrhosis, making a NASH diagnosis before patients become cirrhotic can have important implications for treatment.’ —Rajiv Chhabra, MD

For diagnosis and evaluation of NAFLD and NASH, liver biopsy remains the gold standard method but it is very invasive. Clinicians need useful noninvasive biomarkers that can serve as reliable alternatives. Currently, a set of clinical signs and symptoms, patient characteristics, and laboratory and imaging tests can be used to diagnose and evaluate NAFLD/ NASH noninvasively. However, these markers lack the specificity and sensitivity of liver biopsy in distinguishing NAFLD from NASH and in determining the presence and stage of fibrosis. This study looked at two novel biomarkers—ceruloplasmin and ferritin—and their ability to predict the presence of NASH and the severity of NAFLD, and found a significant correlation between high ferritin levels, low ceruloplasmin levels, and grade of steatosis and level of inflammation. Although the results need to be validated in longitudinal studies, these biomarkers are potentially important additions to the growing pool of diagnostic biomarkers being studied for the noninvasive diagnosis of NAFLD/NASH.

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

By the Numbers: Bad Referrals hances are, a good deal of your practice’s caseload comes from referrals. So it’s frustrating when those patients turn out to be a bust. A recent survey by Kyruus, Inc., found that more than a quarter of referrals were either inappropriate or somewhat inappropriate—because they required a different specialty or

The Cost of Misdirection

subspecialty, referral was unnecessary to begin with, the diagnosis was incorrect or for another reason. The problem isn’t merely academic: According to Kyruus, patients waste nearly $2 billion per year on inappropriate referrals, in the form of lost wages and unnecessary copays.

7.8%

clinically inappropriate referrals

535 new patient referrals per year per MD

patients per MD who are misdirected each year X

Clinically inappropriate referrals, by type 3% 2%

470,000

practicing specialist MDs in the United States

19.7 million

clinically inappropriate referrals every year, 63% of which are re-referred

Assuming …

10%

48%

11%

$50

average copay amount

work hours taken off for an appointment

17%

$25 average hourly earnings

$1.9 billion annually in lost wages and unnecessary copays paid by patients

■ ■ ■ ■ ■ ■ ■

Additional costs to the system include:

Wrong specialist/subspecialist Referral unnecessary (better managed by primary care physician)

•

Delayed patient care

Wrong diagnosis

•

Wasted physician time

•

Poor outcomes

Redundant service

•

Increased readmissions

Other

•

Higher mortality

Additional workup needed Patient required medical management (not surgical)

Source: Kyruus, Inc.

Novel Diabetes continued from page 13

GLP-1 RAs may have other non-endocrine benefits, Dr. Edwards said. Investigators are analyzing potential related improvements in blood pressure, total cholesterol, low-density lipoprotein and triglycerides (Diabetes Obes Metab 2014;129:2305-2312). “These effects are particularly useful in type 2 DM patients, since they frequently have these comorbidities,” Dr. Edwards said. According to Dr. Edwards, a barrier to wider clinical adoption of GLP-1 RAs is the accompanying risk for pancreatitis and pancreatic duct metaplasia. “Given reports of these complications, I would not administer these agents in patients with a history of pancreatitis, alcohol abuse or pancreatic cancer,” she said. But there’s a caveat: The extent of the risk for pancreatitis and pancreatic cancer is disputed, and the FDA said in February 2014 that studies suggest there aren’t enough data showing a direct link (N Engl J Med 2014;370:794-797). However, the adverse effect is listed in the Warnings and Precautions section of the prescribing information for exenatide, liraglutide and albiglutide. Moreover, in a population-based,

case-control study use of GLP-1 RAs within the past 30 days increased the risk for acute pancreatitis by 2.24 times, and use for between 30 days and two years also doubled the risk ((JAMA Intern Med 2013;173:534-539). Despite the risk for pancreatitis, the American Association of Clinical Endocrinologists recommends GLP-1 RAs as a possible first-line monotherapy for patients with type 2 DM who have a HbA1c less than 7.5%, but as part of combination therapy if HbA1c is equal to or greater than 7.5%, Dr. Edwards said (http://bit.ly/1ARfQwo). “Nevertheless, GLP-1 RAs may or may not be available on all formularies.” That lack of access may be a loss for patients, she suggested. “More and more data are coming out showing GLP-1 RAs have the potential to preserve β-cells” (Diabetes Obes Metab 2013;15:485-502).

Afrezza Approval Makes Splash Although SGLT2 inhibitors and GLP-1 RAs are important additions to clinicians’ armamentarium, “the

biggest news in diabetes treatment is the approval of the pulmonary insulin, Afrezza [MannKind],” Dr. Campbell said. “It begins working within minutes, peaks within 15 minutes, and is associated with few instances of hypoglycemia,” he said. The failed launch of Pfizer’s Exubera, another inhaled insulin that was approved by the FDA in 2006 and quickly removed from the market due to low sales, may not bode well for Afrezza. But in Dr. Campbell’s view, differences between the two agents make it more likely that Afrezza will be widely adopted into clinical practice. “Afrezza has greater pulmonary absorption and requires less patient education,” he said. “Patients needed half an hour of training to understand how to use Exubera. Afrezza, in contrast, requires one minute of training.” —David Wild Dr. Strum has served on the speaker’s bureau for Janssen and as a consultant for Insulet, Medtronic and Tandem as a certified insulin pump trainer. Drs. Edwards and Campbell reported no relevant financial conflicts of interest.

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

(NASPGHAN; abstract 414). A society task force conducted the survey as part of a larger effort by the society to assess gender parity in the field, and to determine whether intervention is needed. “People get tired of the idea of gender equality, but it would be nice for people to realize that we are not there yet,” said Laurie Fishman, MD, one of the co-leaders of the task force and a pediatric gastroenterologist at Boston Children’s Hospital. Dr. Fishman, one of the first women and the first part-time faculty member in her department, said she went into

Disparities continued from page 1

But men in the field were much more likely to report that female colleagues had equal pay, mentoring and career opportunities. This disconnect between men and women’s views about gender parity in the specialty was one of the more surprising results of the survey, which was presented at the 2014 annual meeting of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition

the project thinking that NASPGHAN would compare well to other specialties in terms of equity. After all, the organization has had women presidents, and similar to many pediatric fields, it attracts women. “Pediatrics in general is far more friendly to women,” she said. However, the results surprised her. Many women in the society reported being dissatisfied with gender equity in the field. The survey was sent to roughly 1,500 members of NASPGHAN, and 303 (21%) responded. Men comprised 52% of

The #1 best-read gastroenterology publication in the USA. Anytime. Anywhere. gastroendonews.com

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Fecal Transplants for IBD Show Mixed Results in Trials

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BY DAVID WILD

BY DAVID WILD Probiotics may be associated with a reduced risk for hepatic encephalopathy, researchers in India have found. But at least one expert questioned the strength of the findings.

see Probiotics, page 11

Studies Challenge Conventional Wisdom In Biliary Stent Cost BY TED BOSWORTH Chicago—Two randomized trials of metal versus plastic stents for drainage of biliary duct obstruction have reached the same conclusion: Self-expanding metal stents, although they carry higher acquisition costs, are no more expensive than plastic stents because they see Stents, page 13

Chicago—Fecal transplant has reached a critical milestone: testing in the first randomized controlled trial of the therapy to treat inflammatory bowel disease. Although this step might be good for science, the news was not quite so encouraging for patients. The treatment did not appear to be better than placebo transplant at alleviating symptoms of ulcerative colitis (UC), according to the researchers. “Although we did not find a statistically significant effect of FMT [fecal microbiota transplantation] in active UC, there is the possibility that FMT may be effective when administered longer than six weeks,” the researchers said, noting that there were no major adverse events. The study, led by Paul Moayyedi, MBChB, PhD, MPH, acting director of the Farncombe Family Digestive Health Research Institute and director

of the Division of Gastroenterology at McMaster University, in Hamilton, Ontario, Canada, was one of several trials of FMT whose results were presented at Digestive Disease Week (DDW) 2014. In the trial, the researchers randomized 27 patients with mild to moderate UC to receive an FMT enema and 26 patients to receive a placebo

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I N S I D E EXPERTS’ PICKS

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It’ss a common It co complaint: Many physicians who find themselves plugging data into elecctr ctronic health records (EHRs) feel like transcriptionists, not doctors. After all, th heyy say, “I didn’t go to medical school to become a medical journalist” (not, we h w hasten to add, that anything is wrong with that profession). But the world has changed, c and EHRs are here to stay. We asked four individuals who use or aree fam miliar with the software systems in gastroenterology practices how they’ve adapteed d to the new reality—and how those in the specialty who are just making the leap can n lland successfully. see Expert Roundtable, page 22

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Extending Conventional Endoscopy in Barrett’s Esophagus Using Narrow Band Imaging See page 26

EDUCATIONAL REVIEW Advanced Colonoscopic Imaging: Do New Technologies Improve Adenoma Detection?

Advanced Colonoscopic Imaging: Do New Technologies Improve Adenoma Detection? MOHAMMAD TITI, MD Division of Gastroenterology and Hepatology Veterans Affairs Medical Center University of Kansas School of Medicine Kansas City, Kansas

NEIL GUPTA, MD

PRATEEK SHARMA, MD

Division of Gastroenterology and Hepatology Loyola University Medical Center Maywood, Illinois

Division of Gastroenterology and Hepatology Veterans Affairs Medical Center University of Kansas School of Medicine Kansas City, Kansas

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Dr. Sharma has received grant support from CDX Labs, Cook Medical, NinePoint Medical, and Olympus Inc. Drs. Titi and Gupta report no relevant financial conflicts of interest.

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CRC and have shown a reduction iin mortality t lit within the screened population.2 However, colonoscopy remains imperfect and several studies have raised concerns about the miss rate of adenomatous polyps during screening. The overall miss rate is approximately 20%, and ranges from 6% for large (10 mm) adenomas to 26% for diminutive (<5 mm) lesions.3 Missing these adenomas is one of the proposed mechanisms in the development of interval colon cancers that occur within the screened population.4 Improving detection of adenomas during colonoscopy therefore may be the key to more effective screening.

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

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Rise in colectomy for constipation raises alarm ...... page 37

‘People get tired of the idea of gender equality, but it would be nice for people to realize that we are not there yet.’ —Laurie Fishman, MD

the respondents. Only 9% of women, but 46% of men, agreed with the statement that “women earn the same as men” in the field. Those working in academic roles were the most likely to respond that men earn more (40%), whereas those outside of academia were more likely to report that men and women earn the same (37%). Nearly one-third of the women reported that they were dissatisfied with mentoring, compared with 13% of men. Women also were more likely to report feeling uncomfortable with the words or actions of a colleague. The task force did not have data on compensation to confirm if women are indeed paid less, but the association plans to try to collect some salary information to aid the task force’s assessment. Gitit Tomer, MD, co-leader of the task force and associate professor of pediatrics at Yeshiva University Albert Einstein College of Medicine’s Montefiore Medical Center, in New York City, said a lack of transparency about compensation allows gender disparities to persist. “Men and women should have the same salaries for the same jobs,” Dr. Tomer said. Studies of gender equity in medicine overall have documented gender-related differences in salary that are not fully explained by differences in productivity, specialty or rank. And although there are roughly equal numbers of male and female medical students, women remain underrepresented in senior positions. “Unfortunately, despite many great strides toward gender equity in medicine, there is still much room for improvement,” said Reshma Jagsi, MD, DPhil, associate professor of radiation oncology at the University of Michigan Health System, in Ann Arbor, who has studied the issue ((Acad Medd 2013;88:10.1097/ ACM.0b013e3182a71519).

Complex Cases The data on why gender disparities persist in medicine suggest many potential causes, including unconscious gender biases in promotion and compensation decisions, less mentoring for women and less aggressive negotiation by women. Women may also choose career paths different from men, in part to accommodate childrearing responsibilities.

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

In the survey, however, having young children or a having a spouse with a flexible job was not linked to either men or women’s job satisfaction. Male respondents were more likely to report having a spouse with a flexible job (35%), compared with female respondents (14%). But women were more likely to report being dissatisfied with work-life balance than men. “It’s not all just discrimination, or women not working as hard,” Dr. Fishman said. Persistent gender disparities in the medical profession may be detrimental to women’s careers and patient care ((J Women’s Healthh 2008;17:1453-1462). “Adequate representation of women in senior positions in medicine is essential because we know that new insights and

approaches are most likely to be discovered when individuals with diverse backgrounds and life experiences interact,” Dr. Jagsi said. Offering more mentoring and training for women in negotiation may be one way for the NASPGHAN to boost the numbers of women pediatric gastroenterologists in leadership roles, Dr. Tomer said. In the full paper, she and her colleagues write that Johns Hopkins University School of Medicine, in Baltimore, found that a multifaceted intervention increases promotions and salary equity for female faculty ( (JAMA A 1996;11:898-905). They also cite another study that found female faculty reported a decrease in sexual harassment, gender discrimination and gender insensitivity after universal training to reduce these behaviors ((Acad Med 2000;75:464-469). Dr. Jagsi noted that Massachusetts General Hospital has provided funding to support women’s career progress while they raise young children ( Jagsi R et al. Arch Intern Medd 2007;167:343-345). “It’s not just women’s responsibility, but also department leadership,” Dr. Fishman said. “People on top have to take responsibility to do better mentoring to keep things equal.” —Bridget M. Kuehn

Gender Gap an Academic Issue, But Far From Moot PHILADELPHIA— —Women are significantly underrepresented in academic gastroenterology when it comes to research and holding senior faculty positions, new research shows. The good news is that these differences may be due to career duration and could diminish with continued support and mentoring of young women in the field, the researchers said. Sarah J. Diamond, MD, a gastroenterology fellow at Oregon Health & Science University, in Portland, and her colleagues evaluated faculty data from 114 academic programs accredited by the Accreditation Council for Graduate Medical Education in the United States. Of the 2,486 faculty members they studied, 1,894 (76%) were men and 592 (24%) were women. Half of the men held senior faculty positions, compared with 29% of the women (P<0.001). The median career duration was 20 years for men and eight years for women, and the median number of publications was 24 for men and nine for women. Men also had a significantly higher H-index—a combination of publication quantity and scholarly impact— than women: 8 versus 4, respectively.

Because the H-index depends in large part on time—both the duration of the author’s career and the time since publication—the researchers also considered the M-index, a complementary metric that can be used to compare publication productivity among researchers with varying career lengths, by dividing the H-index by the length of the author’s career. “Notably, the M-index was not statistically different between men and women. The differences in productivity disappeared when we accounted for differences in career duration,” said Dr. Diamond, who presented the findings at the 2014 annual meeting of the American College of Gastroenterology (abstract 3). “In our academic cohort, a gender gap in female representation exists, but this gap is similar to that seen in academic medicine as a whole—a trend that suggests female representation [in gastroenterology] is steadily increasing,” she said. “We’re hopeful that efforts to promote early career development among young women will continue to improve trends” in the specialty. —Monica J. Smith

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GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Bariatric Surgery Costs Recouped With Reduced Meds BOSTON—Obese patients who undergo laparoscopic bariatric surgery use significantly fewer medications in the long term than those who do not have the surgery, according to an analysis of national insurance claims. The yearly savings in prescription drug costs four years after surgery was $1,500. “The decreased rate of prescription drug utilization over four years among patients who underwent surgery compared to those in the nonsurgery cohort

may be due to an improvement in comorbid burden post-surgery,” said John Morton, MD, president of the American Society for Metabolic and Bariatric Surgery (ASBMS) and director of bariatric surgery at Stanford University School of Medicine, in Stanford, Calif. Dr. Morton presented the study at Obesity Week 2014 (abstract a103). Previous research examining the effect of bariatric surgery on health care costs has been mixed. An employer claims database

study conducted between 1999 and 2005 estimated the cost of bariatric surgery to be between $17,000 and $26,000, and concluded that downstream savings offset initial costs in two to four years (Am ( J Manag Caree 2008;14:589-596). Another study, a six-year follow-up of 30,000 obese patients who underwent bariatric surgery between 2002 and 2008 and a matched nonsurgical cohort, concluded that bariatric surgery does not reduce overall health care in the long term

Skills Training Assessment Reinforcement

After adjusting for preindex pharmacy costs and comorbidities, pharmacy costs were 22.6% lower for surgery cases than controls at four years post-index.

ASGE Barrett’s Ablation STAR Certiﬁcate Program An Assessment-Based Certiﬁcate Expand your endoscopic skills to meet the need for Barrett’s Ablation in your practice

Acquire the knowledge and skill you need to confidently perform this advanced technique Demonstrate your qualifications and proficiency in performing Barrett’s Ablation Receive a transcript detailing the completed curriculum, earned CME and assessment of performance in Barrett’s Ablation skills ABIM-approved Offer better patient care

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The skills rrequired for endosco opic ablation techniq iques q such as radiofrequ uency ablation (RFA)) or cryotherapy are n not widely offered d in GI fellow wship programs. For establish hed endosccopists, it ca can c be difficult to o develop these skillss.. The ASGE Barrett’s Ablation STAR Certifi ficate Prog gram prepa ares endoscopists to overcome chaallenges, gain g confid dence and demonstraate their “readiness” to perform Barrettt’s Ablation n to medical co olleagues.

Course and Assessment The e Barrettt’s Ablation Program m is specifi fically desig gned to teach core know kn wledge and motor skkills in Barrrett’s Ablattion through case-based sed video sessions and d intensivee, standard dized hand ds-on training. Part articipants complete e several program co omponentts in sequence. Imme mediately follow wing the livve compon nents, partticipants will complete a post ost-test, and d a one-on-one assesssment of a standardized checklist st of skillss. At the conclusion of the pro ogram, participants will receive a tran an nscript of activities th hey have completed and their performance nce on o th he cognitivve and skills assessment components of the program. m. Participa Pa ants who pass the assessment components will receive a Certificate ate of Comple Comp etion. For established endoscopists, this comprehensive package of medical and endoscopic teaching, assessment and subsequent Certificate of Completion for Barrett’s ablation is not available in any other setting.

Skills to be covered Mucosal imaging and lesion recognition Identification of findings that may influence outcomes and selection of appropriate ablation modality Equipment preparation for RF Generator and/or liquid nitrogen Cryotherapy controller settings Circumferential & focal radiofrequency ablation (RFA) Liquid nitrogen Cryotherapy

2015 Barrett’s Ablation STAR Certiﬁcate – Program Schedule Online program

Nov. 2014 – Feb. 2015

Course/Assessment

March 21-22, 2015

Certiﬁcate options T standard The ard assessment for the course includes skills ffor radiofrequen ency ablation (RFA). Participants have th he option of also o participating p in the cryotherapy asssessment and receiv eiving an additional certiﬁcate.

Skills • Training • Assessment • Reinforcement

ASGE STAR Certiﬁcate Program – Barrett’s Ablation The American Society for Gastrointestinal Endoscopy certiﬁes that

John Doe, MD, FASGE Has successfully completed the training and assessment in Barrett’s Ablation as outlined in the ASGE Barrett’s Ablation STAR Certiﬁcate Program The above-named participant has successfully demonstrated acquisition of knowledge and skills in Barrett’s Ablation including • Lesion recognition • Mucosal imaging • Generator settings • Ablation modalities • Radiofrequency ablation (RFA) • Cryotherapy

ASGE President The American Society for Gastrointestinal Endoscopy (ASGE) is dedicated to advancing patient care and digestive health by promoting excellence and innovation in gastrointestinal endoscopy. ASGE promotes the highest standards for endoscopic training and practice, fosters endoscopic research, recognizes distinguished contributions to endoscopy, and is the foremost resource for endoscopic education.

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((JAMA Surgeryy 2013;148:555-562). Dr. Morton pointed out that this latter study predated the accreditation of bariatric surgical centers and use of the laparoscopic approach, both of which have demonstrated lower complications and costs. The study also had a follow-up rate of only 7%. In the new study, investigators analyzed pharmacy costs from the MarketScan Commercial Claims and Encounters database for patients who had a diagnosis of obesity between Jan. 1, 2007 and Dec. 31, 2008. They compared data for patients who underwent laparoscopic bariatric surgery (laparoscopic gastric band or Roux-en-Y gastric bypass; n=2,700) and a cohort of similar matched patients who did not (n=2,700), with 100% follow-up at four years. This nationwide database contains data for approximately 56 million covered lives from all 50 states. The investigators did not include patients if they had evidence of inflammatory bowel disease, familial adenomatous polyposis, noninfectious colitis, cancer of the digestive organs or peritoneum during the year before the index period. The two patient groups were similar, but individuals who had the surgery had higher rates of cardiovascular disease (65.9% vs. 56.7%), acid reflux (24.7% vs. 11.1%) and sleep apnea (39.6% vs. 18.7%). Patients in the surgery group had higher total pharmacy costs at one year after surgery or post-index year ($3,098

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

WE’RE FOR PATIENTS WITH CROHN’S DISEASE After Crohn’s surgery, it is common for the disease to return within a few months despite anti-inﬂammatory medicine. At UPMC, our multidisciplinary team

vs. $2,303), but lower costs in the next three years. At four years, prescription drug costs were $8,411 for patients who had bariatric surgery and $9,900 for those who did not. After adjusting for preindex pharmacy costs and comorbidities, pharmacy costs were 22.6% lower for surgery cases than controls at four years post-index (cost ratio, 0.774; 95% confidence interval, 0.728-0.821; P<0.0001). Reductions were driven by lower antidiabetic, antihypertensive and cardiovascular drug prescription costs. Whereas the proportion of patients receiving cardiovascular prescriptions declined among those who had surgery from one year to four years post-index (42% vs. 40%), it increased among nonsurgical patients (34% vs. 46%). The same trend was seen for antihypertensive prescriptions (surgery, 66% to 59%; no surgery, 59% to 70%) and antidiabetic prescriptions (surgery, 34% to 21%; no surgery, 30% to 38%). Dr. Morton said the first-year increase for the surgery group was likely attributable to medications that patients sometimes receive after surgery, such as pain medicines and proton pump inhibitors. “Whatever cost savings there were around diabetic medications or high blood pressure medications were lost because of those other medications,” Dr. Morton said. Bariatric surgery also affected the total number of prescription drugs used by patients. After multivariate adjustments,

at four years post-index, the number of antidiabetic prescriptions was 74% lower among surgery cases than nonsurgical cases. Similar trends were seen for the number of antihypertensive prescriptions (48.3% lower) and number of cardiovascular prescriptions excluding antihypertensives (48.9% lower). “It is likely that additional medication cost savings may be maintained years following surgery,” Dr. Morton said. Robin Blackstone, MD, medical director of Scottsdale Healthcare Bariatric Center, in Scottsdale, Ariz., who was not involved in the study, called the research relevant. “We are all anxious to prove the value of bariatric surgery,” she said, noting that the study established its effectiveness in reducing medication costs. Dr. Morton said he expected the Affordable Care Act to increase the rates of bariatric surgery. Only 22 states cover bariatric surgery, but a joint initiative from ASMBS and the American College of Surgeons will address expanding coverage to all 50 states. Dr. Morton said his study provides evidence that this expansion will be valuable. — Kate O’Rourke Dr. Morton is a consultant for Covidien and a speaker for Ethicon. Dr. Blackstone is a consultant for Johnson & Johnson and was a principal investigator for an Enteromedics research study.

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.

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GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Real World continued from page 1

Regimens containing sofosbuvir (Sovaldi, Gilead) and simeprevir (Olysio, Janssen) for patients with HCV are performing as well in real-world settings as they did in clinical trials. These findings, presented at the American Association for the Study of Liver Diseases (AASLD) 2014

Liver Meeting, are welcome. Studies presented at the 2013 Liver Meeting (abstracts 133 and 136) revealed that rates of discontinuation and adverse events with the first-generation HCV direct-acting antivirals (DAAs) boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex Pharmaceuticals) were much higher in

Table 1. HCV-TARGET: SVR4 by Treatment Treatment Arm

SVR4

Sofosbuvir/peginterferon/ribavirin in HCV genotype 1

Total, 85%; noncirrhotic, 90%; cirrhotic, 70%

Sofosbuvir/ribavirin in HCV genotype 2

Total, 90%; noncirrhotic, 91%; cirrhotic, 88%

Sofosbuvir/simeprevir with or without ribavirin in HCV genotype 1

Total, 89%; noncirrhotic, 92%; cirrhotic, 87%; genotype 1a, 86%; genotype 1b, 95%

Sofosbuvir/simeprevir with or without ribavirin in HCV genotype 1 patients who failed prior protease inhibitors

Total, 81%; noncirrhotic, 85%; cirrhotic, 79%

the real-world setting than in the trials that led to their approval by the FDA.

HCV-TARGET Trial In the HCV-TARGET study, a consortium of 38 academic centers and 15 community medical centers in the United States, Canada and Germany set out to characterize the use of DAAs in clinical practice (abstract 45). Data from consecutively enrolled patients treated with regimens containing sofosbuvir were obtained from medical records. Four regimens were evaluated: sofosbuvir/peginterferon/ribavirin, sofosbuvir/ribavirin, sofosbuvir/simeprevir, and sofosbuvir/simeprevir/ ribavirin. Roughly half of patients had cirrhosis and half had received previous treatment for HCV. Only 11% of patients were black. Roughly 78% of the genotype 1, noncirrhotic, treatment-naive patients had a baseline HCV RNA of less than 6 million IU/mL.

HCV, hepatitis C virus; SVR4, sustained virologic response at 4 weeks

‘Real-world data was generally

Table 2. TRIO: Baseline Patient and Clinical Characteristics SOF + PEG/RBV

SOF + RBV

SOF + SMV With Total Or Without RBV

consistent with Phase II/III

Male, %

trial data. There was a very

Black, %

low rate of viral breakthrough,

Cirrhosis, %

Treatment-experienced, %

discontinuation and serious

Null responder, %

Prior PEG + RBV + PI, %

adverse events.’ —Donald Jensen, MD

PEG, peginterferon; PI, protease inhibitor; RBV, ribavirin; SMV, simeprevir; SOF, sofosbuvir

Table 3. TRIO: SVR12 by Treatment Treatment Arm

SVR12 Per Protocol

Sofosbuvir/peginterferon/ribavirin in HCV genotype 1

Overall genotype 1, 91%; genotype 1a, 93%; genotype 1b, 87%; noncirrhotic genotype 1, 92%; cirrhotic genotype 1, 89%

Sofosbuvir/simeprevir with or without ribavirin in HCV genotype 1

Genotype 1, 93%; genotype 1a, 92%; genotype 1b, 97%; noncirrhotic genotype 1, 99%; cirrhotic genotype 1, 85%

Sofosbuvir plus ribavirin in HCV genotype 2

Overall, 81%; treatment-naive, 79%; treatment-experienced, 83%

HCV, hepatitis C virus; SVR12, sustained virologic response at 12 weeks

Rates of sustained virologic response (SVR) were consistent with rates found in clinical trials (Table 1), and were high in both cirrhotic and noncirrhotic participants. “There was no difference whether ribavirin was incorporated into the regimen or not,” said Donald Jensen, MD, director of the Center for Liver Diseases at the University of Chicago School of Medicine, who presented the results. The genotype 1a cirrhotic patients had the lowest SVR at four weeks post-treatment (SVR4), and genotype 1b patients without cirrhosis had the highest SVR4 rates. Lower albumin levels, genotype 1a, history of prior decompensation and history of prior triple therapy failure were associated with failure to achieve an SVR. There was a high concordance between SVR4 rates and SVR12 rates. Overall, 5.7% of patients experienced a serious adverse event; 2.1% discontinued treatment because of adverse events; and 0.4% discontinued because of lack of efficacy. “Real-world data was generally consistent with Phase II/III trial data,” Dr. Jensen said. “There was a very low rate of viral breakthrough, discontinuation and serious adverse events.” Adverse events were least common in patients who received regimens without peginterferon and ribavirin. Dr. Jensen noted that use of simeprevir/sofosbuvir was off-label at the time of the study. The FDA approved simeprevir for genotype 1 HCV in combination with peginterferon-alfa and ribavirin in November 2013. The see Real World, page 28

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GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Real World continued from page 26

FDA approved simeprevir in combination with sofosbuvir in November 2014.

TRIO Study A second study presented at the Liver Meeting mirrored the HCV-TARGET results (abstract 46). In this study, data were collected directly from electronic records of specialty pharmacies. Only patients who received 12-week regimens were evaluated (n=955), with roughly

two-thirds treated at academic centers and one-third treated in community hospitals and clinics. Describing the baseline patient characteristics (Table 2), Douglas Dieterich, MD, a liver disease expert at Mount Sinai Hospital, in New York City, pointed out that about three-fourths were genotype 1 and 22% were genotype 2, with a smattering of genotypes 3 through 6. Approximately 50% of patients had a viral load of

less than 2 million IU/mL. Rates of SVR12 with sofosbuvir/ peginterferon/ribavirin, sofosbuvir/ribavirin, and sofosbuvir/simeprevir with or without ribavirin regimens were comparable to data reported in clinical trials, Dr. Dieterich said (Table 3). Cirrhosis was the most important predictor of response to therapy, according to the researchers, while prior treatment failure had no effect on SVR rates. The

Cases in Hyponatremia

Minimizing Risks, Optimizing Outcomes

overall discontinuation rate was 5%, with 3% resulting from nonadherence and 1.9% from adverse events. Steven Gonzalez, MD, attending physician in the Division of Hepatology at the Annette C. and Harold C. Simmons Transplant Institute at Baylor All Saints Medical Center, in Fort Worth, Texas, said the findings were surprising. “A debate has existed in the past regarding whether clinical trials reflect the experience in the real-world setting,” Dr. Gonzalez said. “The impressive efficacy reported in the HCV-TARGET and TRIO cohorts could be attributed to the increased tolerability and adherence associated with interferon-free regimens, as only minimal early discontinuations or serious adverse events were reported in these cohorts.” —Kate O’Rourke Dr. Jensen reported no relevant financial conflicts of interest. Dr. Dieterich has served as a consultant/scientific advisor for and received grants/research funds from Gilead and Janssen. Dr. Gonzalez is on the advisory board of Gilead.

To participate in this FREE CME activity, log on to

www.CMEZone.com/hyponatremia Release Date: November 11, 2014

Expiration Date: November 11, 2015

Faculty

Goal

Michael L. Moritz, MD

The goal of this educational activity is to provide clinicians with clinically relevant information and practice strategies concerning the assessment and management of hyponatremia.

Professor, Pediatrics Clinical Director, Pediatric Nephrology Medical Director, Pediatric Dialysis Children’s Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania

Denise H. Rhoney, PharmD Ron and Nancy McFarlane Distinguished Professor and Chair Division of Practice Advancement and Clinical Education UNC Eshelman School of Pharmacy Chapel Hill, North Carolina

Learning Objectives At the completion of this activity, participants will be better prepared to: 1 Distinguish the various subtypes of hyponatremia. 2 Describe the comorbidities and causes commonly associated with hyponatremia and their signiﬁcance in treatment. 3 Summarize current evidence and best practices in the management of hyponatremia. 4 Explain how to mitigate adverse events secondary to treatment of hyponatremia. 5 Apply strategies to improve the management of hospitalized patients with hyponatremia.

Intended Audience The intended audience for this educational activity includes physicians (cardiologists, critical care specialists, endocrinologists, hepatologists, hospitalists, intensivists, and nephrologists), nurses, pharmacists, and other clinicians who care for individuals with hyponatremia.

Accreditation Statement This activity has been planned and implemented in accordance with the Essential Areas and policies

This activity is jointly provided by Global Education Group and Applied Clinical Education.

of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group and Applied Clinical Education. Global Education Group is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation Global Education Group designates this activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Pharmacist Continuing Education Accreditation Statement Global Education Group is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Credit Designation Global Education Group designates this continuing education activity for 1.0 contact hour(s) (0.10 CEUs) of the Accreditation Council for Pharmacy Education. (Universal Activity Number - 0530-9999-14-061-H01-P) This is a knowledge-based activity

Accreditor Contact Information For information about the accreditation of this program, please contact Global Education Group at (303) 395-1782 or inquire@globaleducationgroup.com.

Supported by an educational grant from Otsuka America Pharmaceutical Inc.

Distributed via CMEZone

F D A U P D AT E & P R O D U C T N E W S

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

he FDA has approved the Third Eye Panoramic attachment for colonoscopes that provides more than a 300-degree view of the colon, according to the manufacturer of the device. Avantis Medical Systems, Inc., said its Third Eye Panoramic clip-on attachment builds on its previously released Third Eye Retroscope by adding a pair of cameras that allow the endoscopist to see to see into folds on the right and left of the scope. Unlike its predecessor, the new device leaves the channel free so that clinicians do not need to take off the attachment before they remove polyps. In a study presented at the 2014 annual meeting of the American College of Gastroenterology, New York researchers using the Third Eye Panoramic device reported an adenoma detection rate of 48%.

I-View Ltd., has received approval from the FDA to market its Aer-OScope colonoscopy system in the United States, the company announced. The single-use, self-propelled device provides a 360-degree view of the colon in all directions, permitting clinicians to see mucosa behind folds, according to the manufacturer. The Aer-O-Scope is expected to be available in the United States in early 2016.

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FREE iPad App Explore the features of the new app on your iPad.

he FDA in December approved Viekira Pak (ombitasvir/paritaprevir/ritonavir), for the treatment of infection with the hepatitis C virus (HCV). The drug, from AbbVie, is intended for patients with genotype 1 HCV, including those with cirrhosis. It can be taken with or without ribavirin. Clinical trials leading up to approval found that between 91% and 100% of patients who take Viekira Pak experience a sustained virologic response at 12 weeks of treatment. A 12-week course of therapy will cost approximately $83,000, according to AbbVie.

Three ways to download: 1. Go to the iTunes App Store and search for Gastroenterology & Endoscopy News. 2. Go to gastroendonews.com/apps and click on the “Available on the App Store” icon. 3. Scan this QR code with your iPad and download the App from iTunes.

Read the #1 gastroenterology publication. Anytime. Anywhere.

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Albumin Linked to Survival Odds in Esophageal Cancer PHILADELPHIA—In patients with esophageal cancer (EC), serum albumin levels may predict outcomes and be a useful marker for guiding treatment, researchers have found. Why albumin levels might correlate with poor outcomes is not clear, experts said, but the relationship likely reflects the nutritional status of patients with the disease. “The overall survival for EC is disappointing, with reported five-year survival

to be less than 5% for advanced-stage disease,” said Zeeshan Ramzan, MD, assistant professor of medicine in the Division of Gastroenterology and Hepatology, at the University of Texas Southwestern Medical Center, in Dallas. “Our goal was to identify predictors of early mortality and determine if this can potentially improve overall survival.” Dr. Ramzan’s group presented their findings at the 2014 annual meeting of the American College of Gastroenterology (abstract P615).

Dr. Ramzan, who also works at the VA North Texas Healthcare System, and colleagues retrospectively reviewed data on all 122 patients diagnosed with EC at their center between 2005 and 2010. Adenocarcinoma was present in 61.4% of the patients and squamous cell carcinoma in 33.4%. (The percentages do not add up to 100% because some patients had cell types that were neither adenocarcinoma nor squamous cell carcinoma.) Esophageal tumors and lower

Advances in Probiotic Therapy For Diarrhea-Associated Illness To participate in this FREE CME activity, log on to

www.CMEZone.com

Release Date: February 10, 2014

Expiration Date: February 10, 2015

Chair

Statement of Need

Intended Audience

William D. Chey, MD

Probiotics can be powerful tools in managing a number of medical conditions. However, effi fficacy may be suboptimal if these agents are not used appropriately. As public interest in the benefits fi of probiotics increases, so does the need for clinical education. Many physicians and patients are unfamiliar with the nuances of probiotic pharmacology, or—with many probiotics available for over-the-counter purchase— may not be aware that their patients are selecting ineff ffective therapies. Thus, it is important for health care professionals to familiarize themselves with the latest research data on probiotic use.

Gastroenterologists, primary care physicians, nurse practitioners, nurses, physician assistants, pharmacists, and other health care professionals involved in the care of patients who may beneﬁt ﬁ from the use of probiotic therapy.

Professor of Internal Medicine Director, Gastrointestinal Physiology Laboratory Co-Director, Michigan Bowel Control Program H. Marvin Pollard Institute Scholar Division of Gastroenterology University of Michigan Health System Ann Arbor, Michigan

Faculty Brooks Cash, MD Professor of Medicine Division of Gastroenterology University of South Alabama Mobile, Alabama

Shanti Eswaran, MD Clinical Assistant Professor Division of Gastroenterology University of Michigan Health System Ann Arbor, Michigan

Goal The goal of this educational activity is to provide clinicians with current evidence and strategies for eﬀecﬀ tive probiotic therapy in a variety of disease states.

Learning Objectives Upon completion of this activity, the participant will be better prepared to do the following: fferentiating characteristics of 1 Review key diff various probiotic therapies, including mechanism of action. 2 Describe the importance of strain specificity fi in the clinical applicability of probiotic therapies.

Estimated Time for Completion 1 hour

Course Format Monograph

Accreditation Statement This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of AKH Inc., Advancing Knowledge in Healthcare, and Applied Clinical Education. AKH Inc. is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation AKH Inc. designates this activity for a maximum of 1.0 AMA PRA Category 1 Credit™. t Physicians should claim only the credit commensurate with the extent of their participation in the activity.

3 Discuss the role of probiotic therapy in clinical digestive ailments. 4 Review strategies for appropriate patient selection and education in the use of probiotic therapies.

Jointly sponsored by AKH Inc. and Applied Clinical Education

Supported via an educational grant from Procter & Gamble

Distributed via CMEZone and Gastroenterology and Endoscopy News

esophageal tumors comprised 26.2% and 73.8%, respectively, and stage at presentation was I in 13.9%, II in 14.8%, III in 25.4% and IV in 40.2% (accurate staging was not documented in a few patients). The researchers first divided the patients into two groups: those with survival less than six months (41) and those who lived longer (81). They evaluated demographic and clinical characteristics, symptoms at presentation and risk factors such as smoking, as well as other variables to identify predictors of early death. “On univariate analysis, we found a few factors that turned out to be significant: decreased albumin at time of diagnosis, poor functional status and high white blood cell count,” Dr. Ramzan said. “But on the multivariate analysis, only serum albumin was an independent predictor of early mortality.” Up to that point, the researchers had been evaluating data on patients at every stage of disease. To investigate if the difference in mortality was due to the presence of more late-stage patients in the early mortality group, they focused on only stage IV patients, again dividing them into early and late mortality groups. “We reviewed all demographic and clinical data in these patients, and again low serum albumin at diagnosis turned out to be an independent predictor of mortality,” Dr. Ramzan said. “Having identified that, we now know that probably the first thing we need to do with EC patients is to evaluate their nutritional status rather than hit them with all the chemotherapy and radiotherapy options we have.” Given that serum albumin has been associated with high mortality for other chronic diseases, Prateek Sharma, MD, professor of medicine at the University of Kansas School of Medicine, in Kansas City, said the latest findings were not surprising. “It’s probably a reflection of the nutritional status of the patient,” Dr. Sharma told Gastroenterology & Endoscopy News. “This was a retrospective, single-center study, and they lump both squamous and adenomatous cancer together, so these results would need to be confirmed in a larger population. If we could show that improving nutritional status in patients with low serum albumin could help increase their survival, that would be beneficial to clinical management,” he added. “But this study does hint at that, and suggests that improving the nutritional status in our patients with chronic diseases and cancer is an important thing to do.” —Monica J. Smith

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Researchers Urge Clinicians To Discuss Sexual Function With IBD Patients

early all women with inflammatory bowel disease—and most of their male counterparts—have experienced some level of sexual dysfunction, but fewer than one in 10 say their physicians talk with them about this issue, new data show. One expert said the findings reflect the uncomfortable reality that both physicians and a “shocking number” of patients face. “We’ve been approaching this issue with a ‘don’t ask, don’t tell’ mentality, because both clinicians and patients find it uncomfortable to bring up,” said Sonia Friedman, MD, associate physician in the Division of Gastroenterology at Brigham and Women’s Hospital, in Boston, and an expert on sexual dysfunction in patients with inflammatory bowel disease (IBD). However, with the release of studies like this one on what is becoming a “hot topic,” Dr. Friedman believes the status quo is beginning to change. “Research like this is really important. Many of our patients are young, and a shocking number have problems with sexual functioning, which is a very important part of quality of life,” said Dr. Friedman, also associate professor of medicine at Harvard Medical School, in Boston, who was not involved in the new study. Tauseef Ali, MD, director of Saint Anthony Hospital’s Crohn’s and Colitis Program, in Oklahoma City, and his colleagues recruited 29 patients with Crohn’s disease (CD) and 18 with ulcerative colitis (UC) to participate in the questionnairebased study. Participants had a mean age of 31 years, and 21 were men. Dr. Ali’s team asked the subjects to complete the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF), as well as several other validated questionnaires measuring clinical disease activity, depression and fatigue. The researchers, who presented their results at the 2014 annual meeting of the American College of Gastroenterology (abstract P1076), found that 66% of men with IBD reported some kind of sexual dysfunction: 81% said they had decreased sexual desire; 52.4% reported erectile dysfunction; and 23% said they had difficulty achieving orgasm over the preceding four weeks. Three-fourths (76.2%) reported feeling dissatisfied with intercourse. Among women with IBD, 61.5% reported experiencing sexual dysfunction. Of these, 96.7% said they had low sexual desire; 54% indicated experiencing difficulties with arousal; and more than 50% reported having inadequate vaginal lubrication, difficulty reaching orgasm, pain

Table. Causes and Treatments for Sexual Dysfunction in IBD Etiology

Action

Increased disease activity

Treat with IBD medications.

Medications: steroids, narcotics, antidepressants

Consider dose reduction, change to a different drug or treatment discontinuation.

Depression

Refer for psychiatric treatment.

Hypogonadism

Refer to a gynecologist or urologist.

Surgery, including ileostomy or ileoanal J-pouch anastomosis

Pelvic floor physical therapy for dyspareunia for women is usually effective. For men, refer to a urologist for treatment of erectile dysfunction.

IBD, inflammatory bowel disease

Start the patient evaluation by taking a sexual history and reviewing use of both prescribed and over-the-counter medications; continue with a psychosocial history; and conduct basic laboratory tests to assess hormone levels. Based on the initial investigations, provide appropriate referrals or patient/partner counseling if necessary, or make medication adjustments if possible.

Figure. The patient-centered framework for evaluation and treatment of sexual dysfunction. during intercourse and overall dissatisfaction with sexual activity. Sexual dysfunction was more common in patients with active disease but the difference was not statistically significant, Dr. Ali’s team found. However, sexual dysfunction was significantly more common among patients with depression (71.4%) than among nondepressed patients (36.5%; P=0.01). P Despite the high prevalence of sexual dysfunction among patients with IBD, only six (8%) said their physicians had inquired into what Dr. Ali said is an “important, yet overlooked, aspect of patient health.” “It’s clear that physicians need to start assessing and addressing sexual function in their clinical practice,” Dr. Ali said. “It can have an adverse effect on quality of life.” Before that shift can take place, clinicians will need to overcome several barriers, including adding another clinical care element to what are most often brief appointments and the complexity of diagnosing and treating sexual dysfunction, Dr. Friedman said. “There are many possible causes and many possible treatments, and gastroenterologists won’t necessarily know who to refer patients to,” Dr. Friedman said. Causes such as medication-related adverse events, depression and hormonal imbalances require different treatments, she said (Table). “The encouraging thing is that there are very effective treatments,” she added. “Most patients can be managed successfully, with a huge improvement in their quality of life.” Dr. Ali said gastroenterologists “must allow patients to feel comfortable and in control when discussing

sexual history. That means thoroughly explaining our recommendations, the limitations of our current medical knowledge when it comes to sexual dysfunction, and ensuring patients are offered a referral if needed. Assuring patients of confidentiality, responding

nonjudgmentally and avoiding some of the more sensitive questions during the first interview are other key components of sexual history taking.” —David Wild Drs. Ali and Friedman reported no relevant conflicts of interest.

GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Non-timely AFP (high risk patients)

Hep B continued from page 1

Dr. Rajbhandari’s study sought to determine if mothers diagnosed with HBV during pregnancy subsequently received the minimal standards of care set by the AASLD and the American Congress of Obstetricians and Gynecologists (ACOG). “The fact that more than one-third of women were getting diagnosed at their prenatal visit was a surprise for us—we did not expect that number to be so high. We wanted to know whether the pregnant women diagnosed with hepatitis B were getting adequate care and follow-up. The answer was, sadly, no,” Dr. Rajbhandari said. “The emphasis on preventing vertical transmission to the infant from the chronically infected mother is appropriate, but should not neglect the followup care of the mother.” Reviewing the medical records of the 243 HBV-positive women who had sought prenatal care at MGH from 1995 to 2013, Dr. Rajbhandari and colleagues found that 32% did not undergo timely liver function test measurements, and 26% never had their HBV DNA measured—a critical test to determine how much virus is in the body so that appropriate treatment can be administered. Nearly half of the mothers (49%) never saw a liver specialist for their HBV care.

and determine how to fix it.” “Here, you have a group of patients— these pregnant women—in whom screening for hepatitis B has become routine, but they only get identified because they are pregnant; and when the baby is born, they fade away,” said Daniel Pratt, MD, clinical director of liver transplantation and director of the Autoimmune and Cholestatic Liver Clinic at MGH. “Oftentimes they look well and feel well, and neither they nor their physicians have the understanding that they need appropriate follow-up or the disease can lead to progressive liver disease and can lead to liver cancer.”

Non-timely US (high risk patients) Never tested HIV Never tested for HCV Never tested for HAV No referral to liver specialist Non-timely HBV DNA Non-timely ALT HBV DNA never measured ALT never measured 0

% off women

‘Oftentimes they look well and feel well, and neither they

Figure. Frequency off poor outcomes in HBV care in wome en post-pregnancy.

nor their physicians have the understanding

AFP, alpha-fetoprotein; ALT, alanine aminotransferase; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; US, ultrasound d

that they need appropriate follow-up or the disease can lead to progressive liver disease and can lead to liver cancer.’ —Daniel Pratt, MD

‘It’s clear from the data that these women are getting lost to follow-up or not getting appropriate care to begin with. It’s a real shame. It is similar to getting diagnosed with HIV and not receiving any follow-up care for it.’ —Ruma Rajbhandari, MD, MPH

About one-third of women were at high risk for hepatocellular carcinoma (HCC) based on AASLD criteria, yet only a third of women in this group underwent timely imaging for the cancer (Figure).

Table. Multivariate Analysis of Factors Affecting Referral to and Care by a Liver Specialist Factors in Referral to and Care by a Liver Specialist

95% CI

P value

Patients in Rural, Remote Locations Fare Worse

e antigen-positive

2.29

0.76-6.90

0.139

Known HBV prior to prenatal testing

1.82

0.83-3.99

0.135

Nationally, about 25,000 HBV-positive women give birth each year, and Dr. Rajbhandari said her study’s findings are generalizable to the urban settings where these women—mostly Asian and African immigrants—are more likely to be. “The inadequate care given to these women in an academic setting like ours, where specialists are readily available, portends ever poorer outcomes in rural or more remote settings,” she said. “I think it is important to figure out where the disconnect between diagnosis and care is

Having a partner’s PCP

0.80-5.04

0.14

Year of HBsAg testing

1.06

0.98-1.14

0.127

East Asian ethnicity

1.87

0.76-4.60

0.174

African ethnicity

1.32

0.38-4.64

0.665

Employed

1.15

0.46-2.84

0.77

Insurance: self pay

1.01

0.23-4.38

0.986

Private insurance

1.44

0.61-3.41

0.402

Positive family history of liver disease

1.1

0.44-2.72

0.839

Peak ALT>19

11.68

2.88-47.40

0.001

ALT, alanine aminotransferase; CI, confidence interval; HBsAg, HBV surface antigen; HBV, hepatitis B virus; OR, odds ratio; PCP, primary care physician

Th his area is one in wh hich improvementss can be made to identify and moonitor patients, added Dr. Pratt, who was n not involved in the researcch. “We know the h b benefits f of screening those babies. We have shown that there are clear benefits in screening these babies, both in terms of health care dollars and making sure they don’t develop chronic infection. But even beyond that, let’s make sure that the moms who are chronically infected are also monitored and treated appropriately.” Dr. Rajbhandari said improvements can readily be made with increased physician awareness and training. “Since HBV infection is already being identified during prenatal visits,” she said, “quality improvement measures that include obstetricians, primary care doctors and hepatologists are strongly needed to ensure that women are appropriately engaged into HBV care post-pregnancy.” —Keely Savoie

GASTROENTEROLOGY & ENDOSCOPY NEWS â&#x20AC;˘ JANUARY 2015

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GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

Biopsy

20%

continued from page 1

This approach may seem counterintuitive because many biopsies of areas that appear to be abnormal on endoscopy, with areas of erythema, inflammation or atrophy, often are histologically unremarkable. If an abnormal area is unlikely to reveal pathologic findings, neither will a normal area, explained Daniel T. Nevin, MD, lead researcher of the poster presented at the 2014 annual meeting of the American College of Gastroenterology. “If they don’t see endoscopically apparent abnormalities, such as erythema, [endoscopists] call the gastric mucosa normal, and many don’t perform a biopsy,” said Dr. Nevin, a gastrointestinal pathologist at Miraca Life Sciences Research Institute, in Irving, Texas. “However, a significant proportion of these [stomachs] are not normal on histopathologic examination. And that is the main point of our study: You cannot confirm normal gastric mucosa by the endoscopic appearance alone. You really need to do a biopsy to tell if it is truly normal.” In the study, the researchers obtained histopathologic, demographic, clinical and endoscopic information from the Miraca Life Sciences database for all of the gastric

biopsies they processed between January 2008 and December 2013. They looked at 53,789 patients with a “normal” stomach and 317,401 patients with endoscopic findings of gastritis. Although histopathologic abnormalities were more likely in the gastritis group than in the normal group, 27% (14,940 of 53,789 patients) of endoscopically normal stomachs had gastric pathology, such as infection with Helicobacter pylori, chronic inactive gastritis, reactive gastropathy, intestinal metaplasia or atrophic gastritis (Figures 1-3). These cases would have been missed if a biopsy was not done because the stomach looked normal through the endoscope, Dr. Nevin said. “Based on our study, if endoscopy is performed, it may be worthwhile for the clinician to biopsy the stomach, regardless of what it looks like endoscopically,” Dr. Nevin said. “This was a simple study, but I think it is important. If you are going to put someone through that procedure, you don’t want to miss anything, and to do that you cannot rely on the endoscopic appearance alone. While clinical indications and clinical discretion is, of course, critical when making the decision whether

15%

10%

Normal stomach

Gastritis

2.61 (2.53-2.70) P<0.0001

1.54 (1.49-1.59) P<0.0001 2.05 (1.96-2.14) P<0.0001 1.19 (1.14-1.24) P<0.0001

H. pylori

CIG

Figure 1. Conditions detected significantly more frequently in the endoscopically normal-stomach group than the endoscopic gastritis group. IM, intestinal metaplasia; CIG, chronic inactive gastritis; RG, reactive gastropathy

to biopsy, our study shows that a normal endoscopic appearance does not always equate to an absence of pathology. We think that clinicians can benefit from this new information.” Not so fast, said Manoop S. Bhutani, MD, director of endoscopic research and development in the Department of Gastroenterology, Hepatology and Nutrition at the University of Texas MD Anderson Cancer Center, in Houston. “This is helpful information from a

pathologic standpoint, but one still has to use one’s clinical judgment when making a decision to biopsy,” said Dr. Bhutani, who is also professor of Medicine and Cancer Systems Imaging at the University of Texas and adjunct professor of biomedical engineering at Houston’s Rice University. If, as an analogy, the purpose of the colonoscopy is to screen for cancer or polyps and the patient has no diarrhea, Dr. Bhutani said he would be hard pressed to justify the additional

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GASTROENTEROLOGY & ENDOSCOPY NEWS • JANUARY 2015

add much to the total cost of an endoscopy. “If a person has sufficient symptoms to warrant an endoscopy, then biopsy should be strongly considered, as a gastric biopsy does not add that much to the total cost of the procedure,” Dr. Nevin said. “If you are going to the trouble and expense of scoping someone, you don’t want to miss out on identifying something like Helicobacter gastritis for a nominal additional cost.” Dr. Bhutani, a member of the editorial board of Gastroenterology & Endoscopy News, noted that although an individual biopsy might not raise the cost of a single

procedure, the effect could be significant on total health care spending for endoscopies—and insurance companies might not pay for the procedure if a stomach looks normal. “I’m in the trenches taking care of patients, explaining my actions to a patient and an insurance company. I have to clinically justify a biopsy if the patient’s stomach looks normal, ” he said. Although the endoscopic biopsies are generally safe, there can be rare complications, especially if the patient is thrombocytopenic or has significant coagulopathy, he added.

But, Dr. Bhutani said, if he had suspicion that the patient had one of the conditions noted in the study or it was clinically relevant to look for one of the conditions, he would consider biopsy even with a normal-appearing stomach. “If you suspect one of these conditions and the stomach looks normal, then yes, I would do a biopsy because of the findings of this study,” he said. “I have to use my clinical judgment and put these very important pathologic findings into the proper clinical context.” — Marie Rosenthal

Figure 2. Photomicrograph of an endoscopically normal-stomach showing chronic active gastritis.

OPT IN Figure 3. Immunohistochemical stain from the same case showing numerous H. pylorii organisms. costs of biopsies to look for microscopic colitis. Clinicians should use the same reasoning during an endoscopy, he said. The patient’s signs and symptoms, clinical history, comorbidities and the “need to know” would be important considerations when deciding to biopsy. Then there is the question of where to biopsy and how many biopsies to take, Dr. Bhutani said. Although the study did not specifically address this issue, it did look at the biopsy sites. The sampling patterns were variable, the researchers noted, with the antrum being the most common site biopsied (67% in the normal group; 79% in the gastritis group), and the corpus was sampled, about 41% in both groups. Random gastric biopsies from unspecified sites were more common in the normalstomach group (7.5%) than the gastritis group (3.8%; 95% confidence interval , 1.88-2.03). Cost, too, is a factor. However, Dr. Nevin said the cost of a biopsy would not

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Hemorrhoids: Evaluation and Management for the Office-based Clinician ERIC FONTENOT, MD

STEPHEN W. LANDRENEAU, MD

Louisiana State University School of Medicine Department of Medicine Section of Gastroenterology New Orleans, Louisiana

The authors report no relevant financial conflicts of interest.

he medical literature on hemorrhoidal disease dates back at least as far

as Hippocrates, who described techniques that will be familiar to practitioners even today. This article will cover the epidemiology,

Internal hemorrhoidal plexus

normal anatomy and physiology, pathophysiology, and classification of

Dentate line

hemorrhoids, with a particular focus

External hemorrhoidal plexus

Figure 1.

my.

Courtesy of Iain Cleator MD, Vancouver, BC, Canada

G AST R O E N T E R O LO GY & E N D O S CO PY N E WS • JA N UA RY 2 0 1 5

Table 1. Classification of Hemorrhoid Grades Grade

Bleeding/Prolapse

Bleeding only; no prolapse

Prolapse with defecation: spontaneous reduction

III

Prolapse with defecation: must be manually reduced

Prolapsed, incarcerated: cannot be manually reduced

arteries directly communicate with each other and branches of their corresponding hemorrhoidal veins.3,4 The hemorrhoidal plexuses are important in maintaining continence, contributing 15% to 20% of the resting pressure of the anus. They also protect the anal sphincter during defecation.4,5 Integral to the support of this vascular network are muscle fibers that originate from the internal anal sphincter. These fibers anchor each plexus and the overlying mucosa, allowing for its return to the correct anatomic position after the downward displacement of the hemorrhoids that occurs during defecation.3,4 Failure of this connective tissue buttress leads to a chain of pathologic changes: dilation of the arteriovenous network, prolapse of the hemorrhoidal plexuses, mucus deposition on the anoderm and perianal skin, itching, and friability of the skin in the affected region. The pathogenesis of hemorrhoidal disease is elusive, with varied factors classically being implicated but typically constipation, straining at defecation, and inadequate fiber intake. More recent evidence questions the role these factors play in the genesis of hemorrhoids,6-8 suggesting there may be no association. However, family history, sex, time spent on the commode, and pregnancy do seem to be associated with the development of the condition.8

excoriations, rash, fistula, mucus and soiling, external hemorrhoids, and prolapsed internal hemorrhoids, as well as any abscesses, areas of fluctuance, or fistula. The most important information gained from the digital rectal examination (DRE) is acquired from the first centimeters of the anal canal. It is in this portion of the DRE that an anal fissure or spasm of the internal anal sphincter will be apparent. Assessment of the intersphincteric groove may show a double sphincter sign, which is widening of this normal space. The double sphincter sign indicates separation of the internal anal sphincter from the external sphincter, and points to concomitant sphincter spasm. Also of note are signs of anal fissuring, which may manifest as a scar, thickening, or even a simple roughening of the normally smooth anoderm.2 Hemorrhoids are classified according to anatomic location: External hemorrhoids are below the dentate line and internal hemorrhoids are above. Internal hemorrhoids are also graded according to a classification scheme developed by Banov and based on degree of prolapse (Table 1; Figure 2).10 Evaluation proceeds to endoscopic examination with at least anoscopy and/or flexible sigmoidoscopy. Full colonoscopy should be performed when bleeding is atypical of hemorrhoids or in the setting of risk factors for colorectal neoplasia.9,11,12 It should be noted, however, that mere endoscopic visualization of the hemorrhoidal cushion in a patient without symptoms of protrusion or bleeding does not equate to hemorrhoidal disease and no such diagnosis should be made.9 Moreover, the technical maneuvers required during retroflexion may lead to nonvisualization or underestimation of internal hemorrhoids because air distension of the rectum may cause traction and reduction of the hemorrhoid. Partial deflation during this maneuver will allow the hemorrhoidal tissue to become more apparent and easier to characterize.2 Our practice is to characterize hemorrhoids as large or small during endoscopy, but determination of grade is based on clinical history and examination.

Management Evaluation Patients will describe virtually any pathology of the anorectum as being caused by hemorrhoids. The clinical investigation of “hemorrhoidal” complaints must necessarily be thorough. Evaluation begins with the history and physical examination focused on the symptoms and signs of hemorrhoids produced by both hemorrhoidal prolapse—pruritus, sensation of fullness or bulging, mucus staining, and fecal soiling—and bleeding—painless, bright red, associated with defecation and seen on the toilet paper, around a hard stool, or in the toilet.9 It must be emphasized that internal hemorrhoids do not cause pain. The presence of pain suggests either thrombosis of an external hemorrhoid or another etiology, such as an anal fissure. The anorectal exam includes inspection for

G AST R O E N D O N E WS .CO M

Medical therapy can be effective in patients with mild hemorrhoidal symptoms. Both dietary and behavioral modifications are recommended. First-line therapy is increased fiber and fluid intake.9,13 Patients also should be advised to avoid straining and to limit toileting time because both have been found to be associated with increased hemorrhoid symptoms.7 Despite the pervasiveness of over-the-counter agents, none of these products have established efficacy.3,9 Rubber band ligation (RBL) is the most commonly performed and effective nonoperative procedure in the management of hemorrhoids.2 Redundant hemorrhoidal tissue is ligated by a rubber band applied with either a flexible endoscope or a rigid anoscope. Ligation of the tissue leads to ischemic necrosis, ulceration, scarring, and finally fixation of the redundant section of hemorrhoidal plexus. In a meta-analysis of 18 trials, RBL

was more effective than sclerotherapy or infrared coagulation in the treatment of grade I to III hemorrhoids and was less likely to require repeated treatments.14 The authors found no significant difference in complications among the procedures, but patients treated with RBL reported more pain. Surgical hemorrhoidecSite of dentate line tomy was more effective than RBL but also led to higher complication rates. Internal When complications from RBL do arise, hemorrhoid they often are self-limiting. In a large, retrospective study, the overall complication rate from banding was about 7% and was confined External to pain, rectal bleeding, and vasovagal symphemorrhoid toms, none of which was severe enough to require hospitalization.15 Figure 2. Grading and types of The severe and even fatal complication hemorrhoids. of pelvic sepsis after banding, suggested by Courtesy of Iain Cleator MD, Vancouver, BC, Canada the onset of severe pain, high fever, and urinary retention, has been documented in case reports and is thought to be exceedingly rare.16,17 Immunocompromised patients, including those Table 2. Approved Treatments for with AIDS, neutropenia, and severe diabetes mellitus, are at increased risk for pelvic sepsis.18 Hemorrhoids Flexible endoscopic ligation versus RBL results in Technique Device Manufacturer a statistically significant reduction in number of treatment sessions required and total number of bands Rubber CRH O’Regan Dis- CRH Medical applied, but carries a greater incidence of postproceband posable HemorCorporation ligation rhoid Banding dural pain.19 There were no differences in postproceSystem dural bleeding or recurrent bleeding at 12 months. It also seems that banding multiple hemorrhoids in a sinShortshot Saeed Cook Medical gle session is a safe and effective approach, but posHemorrhoidal Multiband Ligator sibly at the cost of greater pain, vasovagal symptoms, localized swelling, and urinary retention compared with McGivney Hemor- Miltex a single banding per session.20-22 rhoidal Ligator Hemorrhoid banding may be performed in the Infrared IRC 2100 Redfield endoscopy suite or in the office. If performed during coagulation Corp. endoscopy, clinicians can use cap-fitted devices that are designed for esophageal varices, or hemorrhoidBipolar HET System HET Systems specific banders that run off wall suction. If banding diathermy Ultroid hemorUltroid occurs in the office, it may be performed with a disposMonopolar rhoid manageable banding device using either a slotted anoscope or diathermy ment system the “blind technique” described by Cleator.23 Sclerotherapy involves the injection of a chemical sclerosant at the base of a diseased hemorrhoid that in turn leads to thrombosis, attenuation, scarring, and eventual fixation of the area. It is reserved for grade I Doppler-guided laser photocoagulation (DLC) is a newer procedure in which coagulation of the terminal and II hemorrhoids, and is more effective than medical therapy alone.24 However, sclerotherapy is less effective branch of the superior hemorrhoidal artery is performed than RBL in terms of both initial achievement of sympby laser photocoagulation under Doppler guidance. In a 14 prospective study comparing DLC to RBL, laser treattom relief and prevention of recurrence. ment was associated with significantly lower pain scores, Bipolar diathermy and infrared photocoagulation are greater resolution of symptoms, and better quality of life therapies that induce thrombosis and sclerosis of the in patients with grade II or III hemorrhoids. However, the diseased hemorrhoidal plexus through the use of elecprocedure carries additional costs; the cost of each laser trocautery or infrared radiation, respectively. They are used to treat grade I and II hemorrhoids. There are no probe is roughly 17 times greater than that of the RBL (350 vs 20 euros in the study).26 differences in number of treatments required or complication rates between the 2 modalities,25 but infrared Indications for surgical treatment of hemorrhoids coagulation requires more sessions than RBL.14 include grade IV or incarcerated hemorrhoids, failure

G AST R O E N T E R O LO GY & E N D O S CO PY N E WS • JA N UA RY 2 0 1 5

or technical infeasibility of nonsurgical management, coexisting conditions that require surgery such as anal fissure or symptomatic external hemorrhoids, or patient preference.9,12 In one study, more than 90% of patients were successfully managed nonoperatively, with only 9.3% ultimately requiring surgery.27 When compared with RBL for grade III hemorrhoids, hemorrhoidectomy was more effective but had a higher incidence of pain and complications.14 In the setting of grade II hemorrhoids, surgery leads to lower rates of recurrence compared with nonoperative treatments but is associated with greater pain and prolonged recovery.28 A variety of approaches to surgery have been described, with the distinction between conventional and stapled hemorrhoidectomy being of particular relevance. Conventional hemorrhoidectomy involves excising the pathologic hemorrhoid, then either primary closure in the “closed hemorrhoidectomy” or simple ligation of the hemorrhoidal vessels and termination of the operation in the “open hemorrhoidectomy.”3 Stapled hemorrhoidectomy involves the use of a device that circumferentially excises and staples closed a ring of redundant tissue within the hemorrhoidal plexus. When surgery is indicated, stapled hemorrhoidectomy is associated with shorter operative times, briefer convalescence, faster return of bowel function, and lower rates of pain and postoperative disability than

conventional hemorrhoidectomy.29,30 However, the conventional approach is associated with significantly lower long-term recurrence.30-33

Conclusion Hemorrhoidal disease is a common problem that may be underreported by patients and undertreated by physicians. A careful history and physical examination with particular care in the anorectal anatomy is the initial step. Many patients with different and sometimes insidious diagnoses will ascribe their symptoms to hemorrhoidal disease. As a result, special assessment of the need for further diagnostic examinations, such as colonoscopy, based on a particular patient’s history and initial findings is prudent. Any concomitant conditions such as fissures or sphincter spasm should be addressed if present. Once the diagnosis of symptomatic hemorrhoids has been established, treatment with increased fiber and fluid intake, as well as limiting the amount of time spent toileting, are the most established medical therapies. Given its safety, efficacy, and economy, RBL is a firstline nonoperative treatment. In the setting of incarcerated hemorrhoids or in those patients who fail or are not amenable to initial nonoperative therapies, surgery by conventional or stapled hemorrhoidectomy is an option.

References 1.

Johanson JF, Sonnenberg A. Gastroenterology. 1990;98(2):380-386.

2. Ganz RA. Clin Gastroenterol Hepatol. 2013;11(6):593-603. 3. Corman ML. Hemorrhoids. In: Corman ML, ed. Colon and Rectal Surgery, 4th ed. Philadelphia, PA: Lippincott-Raven; 1998:147-205.

17. Sim HL, Tan KY, Poon PL, et al. Tech Coloproctol. 2009;13(2):161-164. 18. Shemesh EI, Kodner IJ, Fry RD, et al. Dis Colon Rectum. 1987;30(3):199-200.

4. Thomson WH. Br J Surg. 1975;62(7):542-552.

19. Wehrmann T, Riphaus A, Feinstein J, et al. Gastrointest Endosc. 2004;60(2):191-195.

5. Lestar B, Penninckx F, Kerremans R. Int J Colorectal Dis. 1989;4(2):118-122.

20. Lee HH, Spencer RJ, Beart RW Jr. Dis Colon Rectum. 1994;37(1):37-41.

6. Johannsson HO, Graf W, Påhlman L. Am J Gastroenterol. 2005;100(2):401-406.

21. Poon GP, Chu KW, Lau WY, et al. Dis Colon Rectum. 1986;29(12):836-838.

7. Johanson JF, Sonnenberg A. Am J Gastroenterol. 1994;89(11):1981-1986.

22. Khubchandani IT. Dis Colon Rectum. 1983;26(11):705-708.

8. Loder PB, Kamm MA, Nicholls RJ, et al. Br J Surg. 1994;81(7):946-954.

24. Khoury GA, Lake SP, Lewis MC, et al. Br J Surg. 1985;72(9):741-742.

9. Madoff RD, Fleshman JW. Clinical Practice Committee, American Gastroenterological Association. Gastroenterology. 2004;126(5):1463-1473.

23. Cleator I, Cleator M. US Gastroenterol Rev. 2005;5:69-73. 25. Dennison A, Whiston RJ, Rooney S, et al. Dis Colon Rectum. 1990;33(1):32-34. 26. Giamundo P1, Salfi R, Geraci M, et al. Dis Colon Rectum. 2011;54(6):693-698.

10. Banov L Jr, Knoepp LF Jr, Erdman LH, et al. JSC Med Assoc. 1985;81(17):398-401.

27. Bleday R, Pena JP, Rothenberger DA, et al. Dis Colon Rectum. 1992;35(5):477-481.

11. ASGE Technology Committee. Gastrointest Endosc. 2010;72(6):1117-1123.

28. Shanmugam V, Muthukumarasamy G, Cook JA, et al. Colorectal Dis. 2010;12(6):579-586.

12. Wald A, Bharucha AE, Cosman BC, et al. Am J Gastroenterol. 2014;109(8):1141-1157.

29. Sutherland LM, Burchard AK, Matsuda K, et al. Arch Surg. 2002;137(12):1395-1406.

13. Alonso-Coello P, Mills E, Heels-Ansdell D, et al. Am J Gastroenterol. 2006;101(1):181-188.

30. Tjandra JJ, Chan MK. Dis Colon Rectum. 2007;50(6):878-892.

14. MacRae HM, McLeod RS. Dis Colon Rectum. 1995;38(7):687-694.

31. Jayaraman S, Colquhoun PH, Malthaner RA. Dis Colon Rectum. 2007;50(9):1297-1305.

15. El Nakeeb AM, Fikry AA, Omar WH, et al. World J Gastroenterol. 2008;14(42):6525-6530.

32. Giordano P, Gravante G, Sorge R, et al. Arch Surg. 2009;144(3):266-272.

16. O’Hara VS. Dis Colon Rectum. 1980;23(8):570-571.

33. Nisar PJ, Acheson AG, Neal KR, et al. Dis Colon Rectum. 2004;47(11):1837-1845.

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