David A. Johnson, MD

Disclosures

November 06, 2015

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Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. I'm at the 2015 American College of Gastroenterology annual meeting, and aloha from Hawaii—it's a tough place to be—but let me give you an update on some of the top clinical presentations.

The Benefit of the FODMAP Diet for Diarrhea-Predominant IBS

First, a couple of clinical pearls from some of the invited lecturers.

Bill Chey gave a brilliant David Sun Lecture[1] on diarrhea-predominant irritable bowel syndrome (IBS). One of the things that I learned was that this patient population may respond well to the low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet. This is the type of diet that is based on exclusion, so it's very difficult for some patients to take on.

Bill conducted a randomized controlled trial and showed that there was a striking improvement in patients' composite endpoint and their diarrhea endpoint with the addition of the FODMAP diet. However, the caveat is that these patients all had dietitians to counsel them. A gluten-free diet on top of the FODMAP diet did not provide an improvement in the outcome; plus, this may invite some noncompliance because the diet becomes so much more cumbersome.

The take-home message is that for diarrhea-predominant IBS, inviting a dietitian to be part of the management team is critical and is something that I'll include in my clinical practice going forward.

Recognizing Isolated Right-Colon Ischemia

I did a number of lectures at the meeting, including a talk on ischemic colitis.[2]

Isolated right-colon ischemia is something that I told the audience that they really need to not forget. This is just a new face on an old disease, but there is clearly an increasing recognition that the patient with isolated right-colon ischemia has much higher mortality and need for surgical intervention. The typical patient population has comorbidities, such as chronic kidney disease requiring dialysis, coronary heart disease, atrial fibrillation, and chronic obstructive pulmonary disease. The heralding symptom is right-sided abdominal pain, which is very different from the standard ischemic changes among patients with ischemic colitis, and it is often not accompanied by diarrhea and bleeding.

A CT scan is the diagnostic test for all patients with ischemic colitis, but if isolated right-colon ischemia is suspected, the key is to go for a CT or MR angiography. Isolated right-colon ischemia can frequently cause a superior mesenteric artery occlusion. Because this is associated with a very high mortality rate, these patients need to be evaluated expeditiously for potential surgical intervention or interventional angiography. The mortality in this patient population is around 22%, similar to pancolonic ischemic colitis.

The Role of Sleep in GI Physiology

I also did the J. Edward Berk distinguished lecture on sleep and gastrointestinal (GI) physiology and disease.[3]

I invited the audience to consider looking at sleep not only as a composite of time between waking hours but as something that is mandatory for resetting the biologic clock and for health. I discussed how lack of sleep is related to the inflammation incurred in inflammatory bowel disease (IBD), and decreased immunogenicity in patients who have more immune risks. For example, people who are jetlagged are more susceptible to get colds, but there is also a profound effect on the GI system.

We really need to be looking at taking a good sleep history, asking about next-day function in our patients, and looking at ways that we can improve sleep, particularly in our patients with IBD. This may be a self-perpetuating problem in patients who have active disease, and in quiescent disease, it may be a marker for patients who are likely to have a disease flare within 6 months.

Let's move to some of the other presentations. I picked my top 10 in no specific order.

EQUIP-3: Evaluating Adenoma Detection Rates

This study, presented by Michael Wallace from the Mayo Clinic in Jacksonville, Florida, was a report on the Endoscopic Quality Improvement Program (EQUIP) looking at adenoma detection rates.[4] This was an evaluation of an educational program that they had put together. Five large clinical sites were randomly assigned to receive in-person EQUIP training with active feedback and were compared with four control sites that only received the training and feedback at the end of the study. Dr Wallace flew all over the country trying to make this work, so congratulations to him for the excellent effort.

The study showed that there was an increase in adenoma detection rates at the control sites, improving from 36% to 39%; I suspect this was related to a Hawthorne effect. There also was an improvement at the training sites, from 31% to 42%. Because of the sizeable gain in the control group, the comparison between groups didn't reach statistical difference.

This study clearly reemphasized that training can improve adenoma detection rates, and so there is no question that training would be beneficial for sites with low adenoma detection rates.

GEMINI 1 and GEMINI 2: Vedolizumab Maintenance Therapy in IBD

The next presentation included data from the GEMINI 1 and 2 trials.[5] These trials tested vedolizumab for ulcerative colitis and Crohn disease among patients who were on stable doses of immunosuppressants. At US sites, patients discontinued immunosuppressants at week 6, and at non-US sites, immunosuppressants were electively continued. Discontinuing immunosuppressants did not change outcomes associated with vedolizumab, including remission rates, at 52 weeks.

I think the take-home message is that we can at least consider discontinuing immunosuppression in these patients. There was no change in antibody formation in the patients who were taking vedolizumab with immunosuppressants once they discontinued the immunosuppressants. Similarly, we discontinue immunosuppressants a lot of times in patients taking anti-tumor necrosis factor (TNF) agents. Of course, withdrawal of the immunosuppressants may decrease some of the risks that are inherent to combination therapy.

Can Fecal Calprotectin Predict Anti-TNF Agent Pharmacokinetics?

This next study looked at the value of fecal calprotectin in predicting anti-TNF agent pharmacokinetics.[6] In this cohort study of adults receiving infliximab or adalimumab for IBD, an elevated fecal calprotectin was correlated with higher anti-TNF agent failure (ie, failure to induce remission) and lower trough levels of infliximab or adalimumab. In particular, a fecal calprotectin value ≥ 150 µg/g was associated with greater odds of requiring dose escalation.

Another predictor of lower drug trough levels was low albumin, so this may be something that you want to consider if you have a high fecal calprotectin before initiating these agents. These patients may be more likely to require dose escalation, so monitoring them more closely is important, because they may not go into remission as you might expect.

Active Technician Involvement During Colonoscopy

This study from Wake Forest University determined whether or not the participants beyond the colonoscopist (ie, technicians) could improve adenoma detection rates.[7] Technicians were encouraged to actively participate in polyp recognition, reminding physicians about missed folds and withdrawal times at different stages. They were actually able to show an overall increase in the adenoma detection rates.

This is something that demonstrated once again that the team approach is a better way to improve adenoma detection rates, particularly among physicians with low adenoma detection rates, where the rate went from 27% to 36%—and in those with standard baseline adenoma detection rates, it still increased it by 4%.

G-EYE™ Increased Adenoma Detection Compared With Standard Colonoscopy

This next study looked at the G-EYE (SMART Medical Systems, Ra'anana, Israel; Pentax Medical ) and was presented by Dr Seth Gross from New York University.[8] The G-EYE is basically a flexible scope with a reusable inflatable balloon at the flexible bending area of the distal shaft.

What they showed in this large study was an increase in the adenoma detection rate from 32% to 52% in those patients who had the G-EYE, an increased rate of 62% compared with standard colonoscopy. With G-EYE, the polyp detection rate increased by 51%, and the advanced adenoma detection rate also increased [by 55% compared with standard colonoscopy]. The study also showed that there was some incremental value as you started to do therapeutics, such as a complex polypectomy, because you could stabilize/inflate the balloon more and allow less scope slippage.

Potential Risks of Immunosuppressant Agents in Pregnancy

This study looked at the potential risks of immunosuppressants during pregnancy.[9] Using a large database that included nearly 6600 deliveries in women with IBD, they found that 51% [Editor's note: The speaker misspoke; the percentage is 21%, according to the abstract.] of mothers were exposed to medication for IBD (ie, anti-TNF agents, thiopurines, steroids). Among these women, there was no incremental risk of the anti-TNF agents to the fetus. In contrast, steroid use was associated with increased risk for preterm birth, intrauterine growth retardation, and stillbirth. However, this was not case for budesonide, which was not associated with these risks.

A very important point that I learned was that among all of the patients who were on immunosuppressants (regardless of drug class), there was an increased risk for acute respiratory illness within 1 year after delivery. This may be something important to warn mothers and pediatricians about, because the exposure may confer a significant risk for upper respiratory infection within the first year of life.

Endoscopic Ultrasound for Staging Newly Diagnosed Malignant Esophageal Strictures

The next study was from Rob Hawes and his colleagues[10] and tested whether or not endoscopic ultrasound was necessary in patients in whom you put your endoscope and who have an obstructing esophageal cancer. We know that there are recommendations from the National Comprehensive Cancer Network suggesting that endoscopic ultrasound be used to stage these type of cancers. Among the 100 consecutive patients with esophageal cancers included in this study, 46% of them did not allow this passage of a standard endoscope (ie, either 9.8 or 9.9 mm).

They then looked at the staging of these patients, all of whom were presumably staged using a CT scan. The inability to pass the endoscope was associated with 29 times greater odds of advanced disease (ie, T3 or T4). So, you don't need to rush in and send in your dilating team. They can sometimes have a significant fracture rate.

These findings may change the current management strategy and perhaps some of the recommendations in the guidelines from the National Comprehensive Cancer Network. We don't need to push hard for endoscopic ultrasound staging in these patients once we have a CT scan. Independently, if we can get the standard endoscope through, incremental dilation and further efforts with endoscopic ultrasound are not required.

PPI Prescribing Patterns: Gastroenterologists vs Primary Care Providers

This study caught my attention, which was a 19-question survey of primary care physicians (PCPs) and gastroenterologists about the proton pump inhibitor (PPI) rancor and whether or not all of this bad news about PPIs and concerns about clopidogrel, bone fractures, and infections altered prescribing patterns.[11] The survey included 384 gastroenterologists that were compared with 88 PCPs. The alarming thing to me was that the concern about combining PPIs and clopidogrel was still very prevalent (17% of gastroenterologists vs [almost] 29% of PCPs).

What really caught my attention was that if somebody had to go on clopidogrel, only 46% of gastroenterologists and 27% of PCPs elected to continue PPIs. In this situation, 50% of PCPs and [just over] 27% of gastroenterologists said they would change to a histamine-2 receptor antagonist. This is still a fairly high percentage of gastroenterologists, and I'm surprised that they would still be concerned enough to switch to a histamine-2 receptor antagonist.

When asked about patients facing long-term PPIs (eg, patients with Barrett esophagus), 51% of PCPs and 25% of gastroenterologists said they would discontinue the PPI owing to concerns about fracture risk. This really doesn't make sense from an evidence standpoint, and I think we really need to take a step back. PPIs are the standard of care. I have very little concern on the basis of the evidence, particularly as related to clopidogrel. PPIs are associated with a risk reduction for GI bleeding, and we all need to remember that the data on cardiovascular mortality and events are not really evidence-based.

Acute Kidney Injury Among Patients With Alcoholic Liver Disease

This next study dealt with acute kidney injury in patients with alcoholic liver disease.[12] This was a retrospective study that highlighted how acute kidney injury in these patients has a significant impact on mortality and delayed hospital discharge. Defining acute kidney injury as an increase in serum creatinine of ≥ 1.5 mg/dL or a weekly increase of ≥ 0.3 mg/dL, the investigators found that there was an increase in both mortality and duration of hospital stay.

What bothered me about this study was that they used criteria that differed from the well-established criteria from the North American Consortium for the Study of End-Stage Liver Disease, which uses a 50% increase from stable baseline serum creatinine within the past 6 months and/or an increase of ≥ 0.3 mg/dL within 48 hours of admission.[13] These are the criteria that I use in my practice, and I get a nephrologist involved very early on, because these are markers for increased mortality. The point is that we need to do a better job in recognizing acute kidney injury in these patients.

Reducing Vertical Transmission of Hepatitis B

The final abstract that I thought was of interest dealt with cesarean delivery and formula-feeding in patients with chronic hepatitis B virus infection and whether or not these would decrease vertical transmission.[14] There are some data that suggest that these two things have a benefit for decreasing neonatal exposure. We do know that the perinatal acquisition of hepatitis B virus is associated with a very high rate of chronic disease (85%-95%), so the idea in this prospective study was to look at the acquisition of hepatitis B virus in the neonate after delivery and after feeding.

What the investigators found was that there was really no difference in vertical transmission between cesarean delivery and vaginal delivery and between formula-feeding and breastfeeding. There is a little bit of a caveat here: Approximately 26% of the neonates did not have follow-up hepatitis B surface antigen tests at 9 and18 months of follow-up, and they were also missing the hepatitis B e antigen and viral load of the mothers in the antenatal state. We know that such drugs as tenofovir are safe during pregnancy and breastfeeding. It would make sense to try and decrease the viral load in these patients.

Those are my highlights and take-home messages of the American College of Gastroenterology annual meeting. Hopefully this information will be of value to your patients and your clinical practice. Greetings from Hawaii, mahalo.

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