COMMENTARY

It's All Here: Your Guide to the Highlights of Digestive Disease Week (DDW) 2017

David A. Johnson, MD

Disclosures

May 31, 2017

Hello. I am Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

I am back from Digestive Disease Week (DDW) 2017 in Chicago. For those who were there, the weather was great, but the science was even greater. There were about 4360 abstracts submitted, and I have tried to review some of them for you. This is my 30,000-feet view on the abstracts that I thought had an impact.

The Esophagus

Peroral Endoscopic Myotomy

 Let's start at the top: the esophagus.

The group at Hopkins[1] presented a nice comprehensive analysis of gastroesophageal reflux after peroral endoscopic myotomy (POEM) for achalasia. They said that there was a sizable risk for reflux disease after POEM surgery and that patients need proton pump inhibitors (PPIs) and some formative therapy. To me, this is reflective of a good operation. This heralds that POEM is here to stay.

A randomized, multicenter, international trial[2] compared POEM with pneumatic dilation using a 30- or 35-mm dilation protocol in achalasia types I to III. POEM had significantly higher 1-year therapeutic success. Virtually 92% were in clinical remission after POEM and 70% after pneumatic dilation. This reflects a very effective operation. We certainly need to refer these people to centers of excellence. POEM is an emerging standard of care. It is my standard for patients with type III achalasia and certainly could be [an additional option] for any patients offered pneumatic dilation or surgery.

Eosinophilic Esophagitis

We all have seen so many articles on eosinophilic esophagitis. What are the implications of a diagnosis?

Nick Shaheen[3] looked at Barrett's esophagus and the implications of increased life insurance premiums a number of years ago. Now, another group at Chapel Hill[4] looked at corresponding 20 national life insurance companies using male and female base cases. People with the diagnosis of eosinophilic esophagitis paid an extra 19% in insurance premiums, especially if they were in an older population.

Beware when establishing this diagnosis. If you are looking, perhaps, at PPI-responsive eosinophilia, calling it eosinophilic esophagitis in the insurance may have implications for the patient.

Gastroesophageal Reflux Disease

How about using LINX® (Torax Medical; Shoreview, Minnesota), the stretchy magnetic bead "bracelet," for reflux? This magnetic sphincter augmentation has been well studied in primary gastroesophageal reflux disease (GERD) using the endpoint of heartburn. Bell and colleagues[5] looked at this using the primary endpoint of regurgitation. After 6 months, 92.6% of patients had improvement in regurgitation with LINX compared with 8% of those taking PPIs. We do not do very well using PPIs for regurgitation. LINX seems to be emerging as a nice option for people with regurgitation.

Proton Pump Inhibitors and Bone Health

How about PPIs and the issues of side effects? We have talked a lot about this on Medscape, and it certainly was discussed at DDW. This study[6] was a double-blind, placebo-controlled, multicenter, 26-week trial looking at bone density and bone mineralization changes from esomeprazole or dexlansoprazole. This study found no meaningful bone density changes induced by PPIs. We have physiologic and longitudinal evidence. I think this bone fracture thing needs to be put to rest.

Breathing Exercises for Belching and Reflux

One study I thought was of interest was about something I have spoken about before in my Computer Consult section: diaphragmatic breathing. I have used this a lot, particularly for rumination syndrome. This study from Singapore[7] looked at diaphragmatic breathing exercises in the treatment of belching and reflux symptoms. Diaphragmatic breathing—the excursion of the abdomen and not the chest wall—showed significant and durable improvement in patients with GERD, both in their symptoms and in quality of life.

The Stomach

Gastric Per Oral Endoscopic Myotomy

Let's move to the stomach.

A multicenter study[8] presented the initial evaluation of 13 patients who underwent gastric per oral endoscopic myotomy (G-POEM), a pyloromyotomy in the greater curvature of the distal antrum and 5 cm distal to the pylorus, and extending to the beginning of the duodenal bulb. This looked at full-thickness pyloromyotomy and showed benefit as it relates to clinical experience. Notably, it did not change gastric emptying. I am still puzzled as to how this can work; gravity does not necessarily flow easily, and a lot of these people have atonic stomachs and dilation. I still do not find all the data to be strong. It needs to be looked at, perhaps for patients with refractory gastroparesis.

Functional Dyspepsia

How about nonulcer dyspepsia? A randomized, placebo-controlled, double-blind study[9] from Japan evaluated the herbal medicine rikkunshito for functional dyspepsia. Rikkunshito has been discussed at DDW in the past for refractory or persistent reflux disease beyond PPIs. It has a variety of pharmacologic actions, such a stimulation of gastric emptying, regulation of ghrelin secretion, and improvement in stress-induced gastric hypersensitivity, and the same for the esophagus. The results were significant for the treatment group compared with the placebo group. Look at it; maybe it can be an option for your patients.

Gastric Bypass Surgery

What about gastric bypass surgery? Tim Koch and the group[10] in Washington had a nice abstract reminding us about thiamine deficiency after bariatric surgery. About 20% of patients in their study had thiamine deficiency with very indolent gastrointestinal symptoms such as nausea, constipation, and dysphasia. Four patients had cardiovascular or neurologic complications. Think about thiamine deficiency when patients report any vague unusual symptoms after bariatric surgery. This applies to gastric sleeve resection, gastric bypass, and adjustable gastric banding.

The Liver

Nonalcoholic Fatty Liver Disease

Let's move to the liver.

We always tell our patients with liver disease, perhaps a bit too aggressively, "No alcohol." This may not be the best scenario in nonalcoholic fatty liver disease (NAFLD). A study[11] looked at over 1500 patients who had a history of alcohol use, defined as one-half of a drink on average per day. When looking at the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2010, these patients actually did better. More than one drink a day was linked to increased risk for harm. Maybe when counseling patients with NAFLD, [you can suggest] that they consider a little bit of alcohol. Certainly, do not take it away from them if they enjoy it.

Preventing Post-embolization Syndrome With N-acetylcysteine

One study[12] that caught my attention was on the use of intravenous N-acetylcysteine (NAC) for preventing post-embolization syndrome in patients undergoing hepatocellular carcinoma transarterial chemoembolization (TACE). Post-embolization syndrome is a real problem. It is a common complication after TACE, particularly for hepatocellular carcinoma, and is typically characterized by fever and rising transaminases. In this open-label, randomized, placebo-controlled trial, they found a significant reduction in post-embolic syndrome in the NAC group—24% as opposed to 48% in the placebo group. Talk to your interventional radiologists who are doing this. It is something I would welcome as a standard. Certainly, we would like to see more. We have no ideas about the prevention of post-TACE liver failure.

Statins in Liver Disease

One of the things we perhaps do inappropriately in patients with cirrhosis is take away statins. A nice study from Taiwan[13] looked at over 1300 patients [with cirrhosis] and found that statins decrease the risk for decompensation and hepatitis B, hepatitis C, and alcohol-related cirrhosis. Previous data showed decompensation mortality improvement in veterans with cirrhosis due to hepatitis C. This study was in a more global population. Again, do not restrict the use of statins in this patient population.

A small study from India[14] looked at the addition of simvastatin in carvedilol nonresponders with portal hypertension. Carvedilol, a potent third-generation, nonselective beta-blocker, showed promising reduction in portal hypertension. Simvastatin also improves generation of nitric oxide in hepatic endothelial dysfunction patients with cirrhosis. They wondered whether the combination would be better. In 16 patients, they showed a significant response in 42% and an overall response in 80%. Addition of simvastatin to carvedilol in nonresponders with portal hypertension may be an excellent rescue therapy.

Transjugular Intrahepatic Portosystemic Shunting

Let's talk more about cirrhosis and transjugular intrahepatic portosystemic shunting (TIPS). Portal vein thrombosis is a common complication for patients who undergo the TIPS procedure, and it is controversial whether to anticoagulate after TIPS. I invite you to review my recent analysis regarding the hypercoagulable state in cirrhosis, which we think may be the genesis of portal vein thrombosis. This prospective, controlled study[15] looked at warfarin for preventing portal vein thrombosis and maintaining stent patency. The incidence of portal vein thrombosis was 7.7% in the warfarin group and 39.6% in the controlled group. Warfarin did not increase the risk for recurrent variceal bleeding or hepatic encephalopathy. This may be something to talk about with your interventional radiologist.

Hepatitis B

I do not think we do a very good job with hepatitis B. Guidelines written by the American Gastroenterological Association[16] talk about the implications of hepatitis B when using chemotherapy and immunosuppressants. This study[17] from Yale University and Bridgeport Hospital looked at how often patients with hepatitis B serology were treated appropriately before the initiation of chemotherapy in a major hospital network; 6.5% had treatment [after] initiation, and 5% continued to take if for at least 6 months after discontinuation. Our compliance with the guidelines is abysmal. Review the guidelines for patients requiring chemotherapy and immunosuppression, even steroids.

Fibrosis in NAFLD

The prevalence of advanced fibrosis among US adults with NAFLD exceeds the prevalence of US adults with chronic hepatitis C virus (HCV) infection and hepatitis B virus (HBV) infection combined. This study[18] looked at the presence of advanced fibrosis in patients with NAFLD using an NAFLD fibrosis score and AST-to-platelet ratio index. A multivariate analysis found that the prevalence ranged from 9.7% to 23.8%, representing 7.3 to 17.9 million individuals. Look hard at these people, particularly with metabolic syndrome risk. Consider obtaining a fibrosis-4 score or some type of composite, perhaps even a FibroScan®.

Endoscopy After Variceal Hemorrhage

One study evaluated adherence to guidelines for repeating endoscopy in patients with banding after variceal hemorrhage or primary prophylaxis. This high-end study from Columbia University[19] found that only 15% of patients were banded again within 2 weeks, with the average time to follow-up endoscopy ranging anywhere from 16 to 2600 days. If you band them, bring them back. The American Association for the Study of Liver Diseases guideline[20] is 2 weeks.

The Biliary Tract

Same-Admission Cholecystectomy

Let's move to the biliary tract.

This study,[21] primarily from Emory, looked at same-day-admission cholecystectomy, as opposed to delayed cholecystectomy, in patients with mild acute gallstone pancreatitis. The endpoint was development of recurrent pancreatitis. For patients who had delayed cholecystectomy, 11% developed pancreatitis after discharge versus 88% in the delayed-cholecystectomy group. These are patients with significant risk for recurrence, and the strong recommendation—both from a cost and a prevention perspective—is to do cholecystectomy during the same hospital stay.

The Small Intestine

Clostridium difficile Infection in Celiac Disease

Let's move to the small bowel.

Patients with celiac disease get diarrhea, right? We recognize that patients with celiac disease have increased risk for other infections, such as pneumococcal infections, tuberculosis, and influenza. But the incidence of C difficile has not been evaluated to date. This study[22] from Columbia University showed that the risk for C difficile infection was increased (hazard ratio > 2), with an increased risk in both genders and across age groups studied. When people come in with diarrhea and you attribute that to their celiac disease, do not forget C difficile.

Video Capsule Endoscopy

One study that caught my attention was on the use of video capsule endoscopy in patients with implanted cardiac devices. This study[23] looked at patients who underwent 112 procedures—a variety of implantations, from defibrillators to left-ventricular assist devices—and found basically no evidence of adverse events. We have shown this in in vitro studies, so do not be held hostage by what the product label says; you can use these safely. Some hospitals still require cardiologists to stand by when these things are administered.

Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP)

Low-FODMAP diets are something we use more and more in our patients with irritable bowel syndrome. There were a couple of studies that looked at this, showing it was safe and effective, but the emphasis here[24] was the importance of letting FODMAP diets be handled by an expert in nutrition. We are just not adequate, and we would do much better if we would turn this over to a nutritionist.

Fecal Microbiota Transplantation

We have talked about fecal transplant a lot in the past. This small, randomized, controlled study[25] from Sweden evaluated fecal transplant in irritable bowel syndrome. They found a significant benefit for fecal transplant on symptoms compared with baseline. Everybody got better, even the donor that received their own stool back in the placebo group. Further analysis is warranted, but it seems that fecal microbiota transplantation may be a better option for these patients.

Infliximab in Crohn Disease

Some studies came out about infliximab serum monitoring. One was the post-SONIC ad hoc analysis.[26] The SONIC study[27] showed that patients treated with infliximab plus azathioprine achieved higher corticosteroid remission at week 26 versus those on infliximab monotherapy. In this post hoc analysis, they found that these results are probably related to higher levels of infliximab with the use of azathioprine, and that patients who did better on monotherapy also had higher levels of infliximab. We are starting to see a shift toward early monitoring of these patients with trough levels and using levels to guide the use of infliximab or any of the biologic agents at present.

Cardiovascular Risk in Inflammatory Bowel Disease

A study from the group at Mayo Clinic in Rochester[28] recognized the increased risk for myocardial infarction (MI) and congestive heart failure (CHF) in inflammatory bowel disease (IBD). This population-based inception cohort study looked at 649 patients, split fairly equally between ulcerative colitis and Crohn's disease, for a median of 15 years compared with controls. They found that patients with IBD had a significantly greater risk for MI (incidence rate ratio [IRR], 1.97) and CHF (IRR, 1.6). We should look hard at our patients with IBD, particularly those who smoke and those who have diabetes or other risk factors for cardiovascular disease.

Sclerosing Cholangitis IBD

We know that sclerosing cholangitis IBD has an incremental risk for colon cancer. This study[29] from the Janowitz Center at Mount Sinai in New York and The Netherlands looked at two population databases. They found that once you have sclerosing cholangitis IBD, the increased risk of developing a dysplastic lesion beyond low-grade dysplasia was significantly increased. If you had low-grade dysplasia and sclerosing cholangitis, there was a hazard ratio of 3.2 for advanced dysplasia or cancer. This high-risk population needs very high maintenance with annual surveillance.

The Colon

Fecal Immunochemical Test

Let's move to the colon.

Immunohistochemical testing for colorectal screening has become the standard, replacing the guaiac-based testing, at least in the US guidelines. A prospective study[30] looked at the performance of the fecal immunochemical test (FIT); 524 people with a positive FIT at three centers in Belgium were stratified for the use of antithrombotics or aspirin. There was no incremental risk identified for these people being more likely to be FIT positive.

Prevention of C difficile

There was exciting news regarding oral enzymes for the prevention of C difficile and vancomycin-resistant Enterococcus (VRE). This phase 2B proof-of-concept study[31] evaluated the efficacy of ribaxamase, an oral beta-lactamase inhibitor, with IV antibiotics for the prevention of C difficile infection and colonization by antimicrobial pathogens. Ribaxamase is intended to degrade excess antibiotics and to protect the gut microbiome. The relative risk reduction of C difficile infection was 71% with a 44% risk reduction for colonization with VRE. I saw that it was approved as a new orphan drug via rapid-transit evaluation by the US Food and Drug Administration. Stay tuned to hear more about this drug.

Fecal transplant success may depend on the bile acid metabolism of the host who has C difficile. One study[32] found that the microbiome in patients who responded to fecal transplant had a different bile acid metabolism profile than that in those who did not. We are seeing more and more about bile acid metabolism as it relates to C difficile, so stay tuned on that concept. Some new drugs may be directed in that regard.

Adenoma Detection

A somewhat frightening analysis came from a group out of Pittsburgh, Stanford, and Harvard.[33] They used modeling to estimate the interval cancer risk relative to the endoscopist. They looked at high-level adenoma detectors and low-level adenoma detectors. They found that if you are an endoscopist in active practice, in the highest quintile of adenoma detection, you can expect an interval cancer every 4-6 years. If you are in the lowest quartile, you can expect an interval cancer every 2-3 years. Even the best-performing endoscopist should expect this. It makes sense, and we need to do better than that. We need to look at ways not only to recognize adenomas but also to adequately resect the entire adenoma. Performance indicators will take us forward.

Dr Irving Pike, past president and the founder of the Gastrointestinal Quality Improvement Consortium (GIQuIC), had a nice presentation[34] about the increasing adenoma detection rate evident over the national benchmarking standards. There are now over 4000 physicians and over 3.5 million colonoscopies recorded in GIQuIC. We have seen a significant increase in adenoma detection as a result of screening colonoscopies. Composite for male and female, the numbers increased from 28% in 2012 to nearly 40% in 2016. Similar increases were found for surveillance and diagnostic exam. The value of a national registry is critically important. If you are not in GIQuIC, you need to be.

In a study from the United Kingdom,[35] 302 polyps were biopsied or resected over a 5-year period in patients with IBD, and they looked adjacently for any evidence of dysplasia. There was no significant evidence that that made any benefit. With contemporary use of high-definition endoscopy and chromoendoscopy, it is no longer thought to be necessary to endoscopically biopsy normal adjacent tissue.

Familial Adenomatous Polyposis

One interesting study[36] evaluated the effect of COX and epidermal growth factor receptor (EGFR) inhibitors on colorectal neoplasia in patients with familial adenomatous polyposis. This randomized, placebo-controlled study looked at the inhibition of COX and EGFR using sulindac and erlotinib. Erlotinib is well recognized for use in non–squamous cell lung cancer and advanced pancreatic cancer. A study showing benefit for reducing duodenal polyp burden using both agents was published in JAMA in 2016.[37] They looked not only at the colon but also at residual pouches in patients who had undergone surgery. The study was actually stopped at the halfway point because the benefit was significant. There was a net percent change of nearly 90% in patients taking both the COX inhibitor and the EGFR inhibitor. Although this may seem pretty radical, the reduction was dramatic in a patient population that we do not do well in.

Preventing Colorectal Cancer Recurrence

Patients always ask, "What can I do to keep this [colorectal cancer] from coming back?" A study from Hong Kong[38] found that low-dose aspirin may reduce colorectal cancer mortality after curative surgery. In this 10-year population-based study, they looked at over 13,500 subjects and found a risk reduction of nearly 15%-20%. It seems to have value for lowering colon cancer–related mortality and overall mortality. I am now doing this routinely for my patients.

There are substantial convincing data showing that fiber protects against the incidence of colorectal cancer development in healthy individuals, but the use of fiber after colon cancer is now the question. Over 1400 patients in the Nurses' Health Study and the Health Professionals Follow-up Study completed a validated questionnaire.[39] Patients in the highest quartile of fiber intake had over [50%] lower risk for colon cancer–specific mortality and [28%] lower risk for all-cause mortality compared with those in the lowest quartile. Of note, reduction was different for different fiber sources. Vegetable fiber was associated with lower risk for colon cancer–specific mortality compared with cereal or fruit fiber. Vegetables seem to be the answer.

Hopefully these data give you perspective for new things to look for. Some things can be taken home and used now. I am Dr David Johnson. Thank you for listening.

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