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ACG 2012: Overview

Hello. I am Dr. David Johnson, Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. I just returned from the 81st Annual Meeting of the American College of Gastroenterology (ACG) in Las Vegas.

Vedolizumab for Inflammatory Bowel Disease

The world of inflammatory bowel disease (IBD) has been explosive. Three studies about maintenance therapy caught my eye. One study looked at vedolizumab, which is an alpha-4B7 integrin gut-selective antibody. If you remember, there was concern with natalizumab about the development of the debilitating polyneuropathy and progressive multifocal leukoencephalopathy that are seen with Creutzfeldt-Jakob disease. These findings really limited the availability of this drug, and it is now used in multiple sclerosis. Now we have vedolizumab, a similar drug that is gut-selective.

Brian Feagan presented the data[1] on vedolizumab in ulcerative colitis. Steve Hanauer presented the data[2] on the maintenance study in Crohn disease. Both study endpoints were at 1 year, and they targeted mucosal healing as well as symptom relief.

The drugs were highly effective relative to placebo, and the 4-week dosing seems to be more effective than the 8-week dosing. But the drug was strikingly better, for some reason, in ulcerative colitis. It was highly statistically significantly better in both ulcerative colitis and Crohn disease, by a factor of 3 times in Crohn disease and about twice as effective as placebo in ulcerative colitis. We don't know the reason for that, but I am excited about the lack of evidence for any type of neurologic consequence, and there was no evidence of opportunistic infections with this drug.

In the ulcerative colitis trial, 32% of the patients had previous nonresponse to anti-tumor necrosis factor (TNF) agents, and that number was closer to 50% in the study for Crohn disease. This is an option that we may be able to use in patients in whom anti-TNF agents have failed, or perhaps move to earlier for induction and remission in both ulcerative colitis and Crohn disease.

The same new drug was evaluated in the PURSUIT study, presented by Bill Sandborn.[3] This is golimumab, another anti-TNF agent. It was compared with placebo, and was highly effective in maintenance therapy for Crohn disease, but 4 cases of tuberculosis developed in this study. One case was disseminated tuberculosis, and it caused the patient's death. It reminds us that as we are using some of these agents for maintenance therapy, we need to be cognizant of opportunistic infections, especially when we are prescribing them for diseases that require long-term maintenance therapy.

The QuantiFERON® (Cellestis; Valencia, California) evaluation of patients who had endemic exposure to tuberculosis brought home the point that safety needs to be emphasized in monitoring these patients routinely in your practice. Recognize too that one of the Physician Quality Reporting System measures for 2012 is appropriate screening for tuberculosis before initiation of these drugs, and the second measure is screening for hepatitis B surface antigen in patients with IBD.

Irritable Bowel Syndrome: Not Just Functional

Let's take it a step further and look at irritable bowel syndrome (IBS). We were all taught that IBS is functional. A very interesting study[4] was presented by the group at California Pacific in conjunction with Salix. It was an industry-sponsored trial of mesalamine in patients with IBS. It took us a while to follow the data that were primarily championed by Mark Pimentel, showing that IBS might have an infectious component.

Patients with diarrheal-predominant IBS were randomly assigned to receive mesalamine 1500 mg daily or placebo. Compared with placebo, mesalamine was associated with significant improvement. The benefit is hard to understand, and when questions emerged about this particular study, it was revealed that not every patient was appropriately screened for microscopic colitis. There was also some question about what mesalamine does to the natural microflora in the small and large bowel.

I dismissed these data initially, saying, "Well, they're interesting, but why would 5-aminosalicylic acid work in IBS?" Then some very provocative work was published by Dr. Julia Liu and her colleagues in Edmonton and Calgary, Alberta, Canada.[5] This study looked at confocal changes that were evident in patients with IBS. The investigators performed retrograde intubation of the terminal ilium and, using confocal technology with a probe, were able to identify (in a prospective fashion, but blinded to the biopsies being read by pathologists) whether these patients had IBS or normal bowel.

The patients with IBS had a higher histologic and confocal potential, what is called an increased "gap density." This means that there was a higher dropout of some of the epithelial cells, something that has been evident in patients with IBD. Patients with IBS have increased gap density dropout. Most patients had IBS diarrhea-predominant (IBS-D) disease, and 2 had IBS constipation-predominant (IBS-C) disease. This blinded trial provided provocative evidence of histologic abnormality identified by noninvasive imaging with confocal technology. In some of these patients who have functional disease, microflora changes might induce gap dropout in the epithelial cells. It starts to make sense that an anti-inflammatory agent might be of some benefit. It's something to consider when we look at patients with IBS, particularly IBS-D. It's not just a functional disease anymore.

NSAIDs for Prevention of Post-ERCP Pancreatitis

A very interesting study[6] was presented on changing patterns of care for those who do endoscopic retrograde cholangiopancreatography (ERCP). This came from a group at Johns Hopkins, and it was a meta-analysis of pancreatic stenting and use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of postintervention pancreatitis. The analysis included 7 studies and a total of more than 1200 patients. Five studies looked at prophylactic pancreatic stenting, 1 study compared stenting and NSAID therapy, and 1 study used rectal NSAIDs (indomethacin).

The study had some striking findings. Pancreatic stenting is better than not stenting, but the administration of rectal NSAIDs is the trump card, with a relative risk reduction of 61% compared with pancreatic duct stenting.

So, in high-risk pancreatic interventional cases, think about using NSAIDs; this should be part of your standard practice. That would be my standard practice for interventions on high-risk patients (prolonged multiple cannulations, sphincter of Oddi, patients requiring a number of pancreatic manipulations). These patients should be given rectal NSAIDs. It is very easy to do, and the potential value is high. It is much quicker and easier than placing a pancreatic stent, which obliges the patient to come back for pancreatic stent removal. I was convinced that this is the real deal and should be the standard of care.

Cystic Lesions of the Pancreas

A very interesting study on cystic lesions in the pancreas came from Linda Lee and her colleagues at Brigham and Women's Hospital.[7] We are all puzzled about the best approach when we find cystic lesions of the pancreas, particularly cystic adenomas (nonprecancerous). We wouldn't be concerned if we could identify them as nonpremalignant cysts, but mucinous cyst neoplasms or intraductal papillary mucinous neoplasms (IPMNs) are premalignant conditions.

Dr. Lee and her colleagues looked at a panel of 4 different profiles for micro-DNA analysis, from paraffin blocks. Most were obtained by fine-needle aspiration, and basically these cysts were aspirated. In separating cyst adenomas (nonprecancerous lesions) from IPMN lesions (precancerous lesions), these profiles were in the range of 85% sensitivity and specificity of nearly 100%. In separating IPMNs from mucinous cyst neoplasms, sensitivity and specificity in 69 patients were both 100%.

This is something that we really need to stay tuned to. Those who do ERCP or pancreatic endoscopic ultrasonography rely on carcinoembryonic antigen (CEA), mucinous differentiation, cytology, and KRAS. Some of these tests are sensitive but not very specific, and others lack sensitivity and specificity. So, this study caught my eye. Although tested in only 69 patients, with the sensitivity and specificity that was described, this could set the standard of care for management of cystic lesions of the pancreas.

Reflex Testing for Hereditary Colon Cancer

We heard a couple of very profound lectures, some of which were from invited lecturers. The Emily Couric lecture was given by Dr. Carol Burke,[8] on hereditary colon cancer. One of the take-home messages was that in your patients with cancer, you should work with your hospital pathologist to develop a protocol for reflex testing of patients who have right-sided cancers, early cancers, or multiple neoplasias that potentially represent a syndromic cancer. The default should be immunohistochemical staining, looking for the next step for detection that would lead to Lynch syndrome or one of the variants thereof. This should be part of the reflex testing.

A recently published study[9] looked at this issue and found that reflex testing is very rarely done, even in centers of excellence. So, go back to your hospital system and talk to your pathologists. When colon cancer is identified, consider early reflex testing by immunohistochemical staining. It is very easy to identify at least who should be moving on to the next stage for serologic testing, and potential identification of Lynch syndrome.

Fecal Transplantation for Persistent C difficile Infection

Dr. Larry Brandt[10] gave the American Journal of Gastroenterology Lecture on fecal transplantation for persistent Clostridium difficile infection, and the concept of the microflora changes that we can induce by fecal transplantation. I became even more convinced that this is an emerging standard of care. I recorded a video commentary on this topic recently. Fecal biotransplantation is easy. Use it in your practice.

Dr. Brandt's topic was very much on target. A National Institutes of Health-sponsored trial that he is conducting at present will give us more information, but I wouldn't wait for that, having used it several times in my own practice. It's a very simple procedure to master.

ACG 2013 will be in San Diego, California, so if you missed it this year, I look forward to seeing you next year. There are lots of evolutionary changes in gastroenterology, and that is what makes it fun for us all.

Thanks for listening. I look forward to talking to you again soon.

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