COMMENTARY

Practice-Changing Highlights From DDW 2018

David A. Johnson, MD

Disclosures

June 18, 2018

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

I recently returned from attending Digestive Disease Week (DDW) in Washington, DC, and would like to share my takeaway messages from this year's meeting, some of which will affect our practice in the short term and others in the long term.

Alcoholic Hepatitis

Alcoholic hepatitis is a disease that we may have been dismissive of as it relates to patients being referred for liver transplant. Mortality is high. Most transfer centers recommend that we not refer such patients for transplant unless they have been abstinent from alcohol for 6 months.

A study[1] reviewed the practice patterns of transplant centers. Of the 45 surveys completed, 23 performed liver transplants in patients who were actively consuming alcohol. The authors found good results in these patients. The majority reported [1-year post-transplant survival rates] of 90% for patients who underwent liver transplantation despite active alcohol consumption. Much of the study[1] relates to the social aspects of identifying patients who would abstain from alcohol post-transplant and those who would suffer a relapse.

Regarding patients in your practice who have alcoholic hepatitis and an associated high mortality risk, you will need to discuss [this study] with your transplant centers to determine whether they might consider such patients with alcoholic hepatitis for liver transplant if they qualify.

Anti-TNF Agents and IBD

Several presentations looked at the effects of anti-tumor necrosis factor (TNF) agents, which is something we use all the time to treat patients with inflammatory bowel disease (IBD). Among these presentations, there are two that I think are game-changers.

The first is a multicenter prospective study[2] that evaluated exposure concentrations of anti-TNF agents in breastfed infants of more than 1450 patients who received primarily biologic therapy for IBD. The authors looked at the levels of biologic agents in breast milk and the developmental milestones in exposed infants over the course of the following year, post-delivery. The authors found no significant transfer of these biologic agents to the patients' breast milk, and that the presence of these agents in the breast milk did not interfere with the developmental milestones for these infants at 1 year. These findings make sense when you consider that the predominant immunoglobulin in breast milk is immunoglobulin A (IgA) and the subclass of the anti-TNF biologic agents is primarily immunoglobulin G (IgG) and should not cross over into the breast milk, and that is in fact what we see.

The second study on anti-TNF agents relates to surgery. We always struggle when surgeons want us to take patients off anti-TNF agents for a period of time prior to a surgical procedure. A lot of these patients are older with arthritic complaints and may qualify for joint replacement surgery. This retrospective case-control study[3] looked at more than 1400 patients with IBD who underwent knee, hip, or shoulder replacement [from 2004 to 2016]. With the exception of prednisone, the authors found no significant increase of serious infections in the patients who were taking anti-TNF agents or another immunosuppressant agent. Taking patients off prednisone or using a prednisone-sparing-type approach makes good sense. Talk to your surgeons [about these study findings]; we can continue these medications, and there is not a significant concern in doing so going forward.

Malnutrition

The next game changer relates to nutrition—something that I think we as gastroenterologists give a bit of lip service to.

This respective cohort study[4] looked at approximately 8700 malnourished, hospitalized patients. Malnutrition was defined as weight loss of greater than 10 lb over the past 3 months prior to hospital admission or a decreased oral intake for 5 days during or prior to hospital admission. These criteria compound the number of patients evaluated. When the authors looked at the logistic likelihood for readmission within 30 days, it was 10% fewer readmissions if the patients had an oral active nutritional supplementation. The reduced number of readmissions was even more significant in oncology and intensive care patient subpopulations. In the oncology subgroup, there was a 22% reduction in hospital readmissions and 51% in the intensive care group.

I am implementing changes in my own practice; I am looking to add a dietitian and offer oral nutritional supplemental counseling.

Polyp Resection

The next study involves polyp resection.

Although we may refer some patients who have large polyps (≥ 2 cm), one question we always have relates to how aggressive we need to be when clipping larger polyps.

A multicenter, randomized study[5] looked at the rate of rebleeding in patients following resection of large polyps (mean size of approximately 4 cm). The most significant difference [with respect to postprocedural bleeding was seen] in clipping the right colon compared with the left colon or transverse colon. The right colon was defined as proximal to the transverse colon. The rate of bleeding tripled if you did not clip the right colon (placebo control vs active clipping). Although bleeding was more common among patients on antithrombotic or anticoagulant therapy, the measured effect of clipping—regardless of whether it was performed on the right or left colon—was similar to that of patients who were not on antithrombotic or anticoagulant drugs.

Fecal Microbiota Transplantation

Clostridium difficile

Fecal transplant certainly has transformed the manner in which we approach patients with C difficile. A group from Norway,[6] who coincidentally had a letter published in the New England Journal of Medicine[7] at the same time that they were presenting, looked at active transplant in the face of active disease as a primary intervention for C difficile; they had a cure of around 57%, and 45% for those patients who received antibiotics. Looking at the active intervention, this cure seemed pretty low to me. I do not know if this is due to the way in which the transplant was administered. These transplants are administered rectally, and they did not have an active prep. Regardless, fecal transplantation is something that we may have more reason to consider early in the treatment of patients with C difficile. This is a proof-of-concept study, and phase 2 and 3 studies are planned.

Irritable Bowel Syndrome

Two other presentations reported on fecal microbiota transplantation as a potential treatment for IBS.

The first is a randomized controlled trial[8] on [fecal transplantation as a potential treatment for] IBS with predominant bloating. It significantly improved the symptoms of patients who have IBS with the predominant symptom of bloating, and also reduced secondary symptoms, such as stool frequency and pain thresholds.

In contradistinction, a randomized controlled trial[9] studying the effects of fecal transplantation in patients who have IBS with diarrhea (IBS-D) found no significant difference to overall primary benefit. There was, however, a subset analysis suggesting a benefit in patients with postinfectious IBS.

So, more to come on fecal transplant. I think microbiome transfer is going to be an emerging technology to treat other conditions in the future. In regard to treating IBS, I think it [fecal transplant] is yet to be determined.

Chromoendoscopy at Colon Preparation

We have seen that chromoendoscopy is very helpful in detecting colorectal dysplasia, particularly in patients with IBD and in some of those with Lynch syndrome. New chromoendoscopy techniques include the addition of methylene blue-MMX tablets, and we have seen this as it relates to some of the 5-aminosalicylic acid drugs and budesonide products in IBD. A delayed-release formulation permits deliverance of the dye to the colon when combined with the colon preparation.

A multicenter international study[10] looked at methylene blue powder incorporated in an MMX tablet for a targeted release of the dye at the colonic level. In the hands of experts, this technology led to an 8% incremental gain in the overall adenoma detection rate (ADR). Of particular note, experts who administered treatment in the placebo group had an ADR of 48%, which is way beyond the normal minimum threshold. So, you had super-experts doing this and still there was an advantage of 8%.

What I found particularly exciting about this technology is that it increased not only the sensitivity but also the specificity; one is not simply removing more polyps due to enhanced visibility but also neoplastic polyps and sessile serrated polyps requiring resection.

This technology is currently pending approval by the US Food and Drug Administration and hopefully will be available soon. It is going to be a game changer by increasing adenoma detection and enhancing adequate resection by providing better identification of the margins.

Artificial Intelligence and Polyp Detection

The other area that I found particularly exciting relates to the development of artificial intelligence for polyp detection. Artificial intelligence has been used in computer-assisted detection technologies to improve breast cancer screening and to evaluate pulmonary nodules on chest x-rays and CT scans. Now experts are using artificial intelligence to enhance colonoscopy.

Karnes and colleagues[11] at the University of California, Irvine, asked four expert colonoscopists (ADR ≥ 50%) to review nine colonoscopy videos and identify all polyps present in each video. Then, using a neural network that they had developed to identify polyps, they trained a computer to take a second look at what the experts identified as polyps. Lo and behold, use of the neural network led to an increased polyp detection rate of 20% over that of those identified by the experts.

We will see more on the application of artificial intelligence as a technology superimposed onto what we already offer. Again, this technology is extremely exciting and is now moving into the field of gastroenterology.

These are my key takeaways from the meeting. Some will be game changers to our practice; some will have an immediate effect on practice, while others will affect how we manage patients in the long term. There continue to be exciting advances in gastroenterology. We will look forward to seeing these [studies] in manuscript form to formally evaluate further, but there are a lot of things that I think we can start to apply now.

I am Dr David Johnson. Thank you for listening.

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