2015-09-11 14:55:52 UTC

Finding the Sweet Spot: Proceed with Caution

Sept. 13, 2015

There were some problems with the endoscopic anti-reflux procedures in the past.

John Pandolfino

John E. Pandolfino, MD

Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago IL

Read the other half of this AGA Perspectives point-counterpoint debate: Finding the Sweet Spot: Endoscopic Treatment is Back

Before I start this counterpoint, I would like to begin by stating that I have a huge conflict of interest in that I really want something to work for my refractory gastroesophageal reflux disease (GERD) patients. Each day I go to clinic, I struggle with the large number of patients who are presenting to me with the complaint of continued symptoms despite proton pump inhibitor (PPI) therapy. By most estimates, approximately 40 to 50 percent of patients are not satisfied with PPI therapy and PPIs have a marginal benefit in regurgitation and cough.1

Now it is true that at least 50 percent of these patients do not actually have reflux and this represents an entirely different problem that shouldn’t play into this conversation, as these patients should never have therapy directed at an escalation of reflux treatment. However, there is a small group of patients who have truly refractory GERD despite a compliant trial of optimized PPI treatment of at least 8 to 12 weeks. They continue to have erosive esophagitis or continued symptoms in the context of acid exposure on PPI therapy and I wish I could offer a therapy that was cheap, non-invasive and effective.

Unfortunately, there is no therapy that fits this profile and thus I am left with a careful discussion with my patients focused on balancing the risks and benefits of the medical, surgical and endoscopic options. Certainly if a patient has disrupted anatomy and a large hiatus hernia, the options here are very limited and I feel very comfortable sending them for anti-reflux surgery and hernia repair. I have a harder time with patients who have a small hernia or seemingly normal anatomy who continue to have objective findings of continued pathologic acid gastroesophageal reflux; I would love to have a less invasive option than surgery for these particular patients. Although surgery is also effective in this patient population, it still has significant risks of dysphagia, gas and bloating, and there are many patients who are searching for a less-invasive approach.2


Obviously, there were some problems with the endoscopic anti-reflux procedures in the past, and now that they are back, we should proceed with caution.


When confronted with these patients, I typically try to encourage weight loss, make some minor dietary changes that target the pattern of reflux and work my way through a myriad of medications, such as baclofen, alginates and, potentially, promotility agentsif the patient has evidence of gastroparesis. The overall yield of this approach is marginal and we need something better. One potential class of therapy that has been put forward as an option for these difficult patients is focused on endoscopic augmentation of the anti-reflux barrier and thus endoscopic antireflux therapies are making a comeback. Theoretically endoscopic therapy makes sense, as the primary determinant of reflux is movement of gastric refluxate through the anti-reflux barrier. The endoscopic techniques attempt to do this via a variety of mechanisms, such as suturing, plication, bulking and delivery of radiofrequency energy to reduce compliance through muscle hypertrophy or fibrosis. The excitement regarding these techniques has always focused on this biologic plausibility.

With this in mind, I am always reminded of the quote by George Bernard Shaw, “If history repeats itself, and the unexpected happens, how incapable must man be of learning from experience?” Obviously, there were some problems with the endoscopic anti-reflux procedures in the past and now that they are back, we should proceed with caution.3

Two devices, Stretta (Mederi Therapeutics Inc., Norwalk, CT) and EsophyX (EndoGastric Solutions, San Mateo, CA), are FDA approved and currently being used in clinical practice. The Stretta procedure was first approved by FDA in 2000, and was one of the earliest endoscopic devices conceived to treat reflux. The ultimate goal of Stretta is to augment the anti-reflux barrier and the mechanism of action is theorized to be secondary to the remodeling of the lower esophageal sphincter (LES), induced by the application of radiofrequency energy.There have been questions regarding its efficacy in terms of overall effect on LES tone, esophageal acid exposure and PPI utilization when one assesses randomized clinical trials.5

However, one consistent effect is a reduction in symptoms and although this cannot be correlated directly with objective measures, the safety profile of the procedure is acceptable.6 Thus it is reasonable to further assess where Stretta may help in terms of the truly refractory patient population. Although transoral incisionless fundoplication (TIF) saw some setbacks with devices like the NDO Endoscopic Plication System (NDO Surgical, Mansfield, MA) device leaving the market, there is renewed interest in this approach and a newer device, EsophyX (EndoGastric Solutions), is currently being used in clinical practice. The main difference with EsophyX is the ability to perform circumferential, transmural plications that more closely mimic fundoplication. Recently a multicenter randomized controlled trial was performed that assessed EsophyX plus placebo with a sham surgery and PPI therapy.7

The results from this trial suggest that EsophyX is able to reduce troublesome regurgitation in a larger proportion of patients than PPIs alone (67 percent vs. 45 percent). Additionally, there was a significant reduction in acid exposure compared to the PPI treatment group. However, the main issue with all of the plicator devices has been the durability of the procedure and we will need to wait and see whether this plication device will hold up.

So, in the end, endoscopic anti-reflux procedures are not really back, as they were never really gone. Suboptimal efficacy, major complications and issues with durability lessened the enthusiasm in the past and our current desperation to help these difficult patients has brought these tools back into our armamentarium. The good news is that refinements to these techniques have made them safer and probably more effective. Hopefully we have learned something from our previous experience and history will not repeat itself. As more trials are performed that support true efficacy above and beyond PPI therapy, I will gladly welcome these devices back with open arms

Dr. Pandolfino is a speaker for AstraZeneca and Takeda, and serves as a consultant for EndoGastric Solutions.

References

1. Kahrilas PJ, Howden CW, Hughes N. Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am J Gastroenterol 2011;106:1419-25; quiz 1426.

2.Richter JE. Gastroesophageal Reflux Disease Treatment: Side Effects and Complications of Fundoplication. Clin Gastroenterol Hepatol 2012.

3. Pandolfino JE, Krishnan K. Clinical Perspectives:Do endoscopic anti-reflux procedures fit in the current treatment paradigm of GERD? Clin Gastroenterol Hepatol 2013.

4. Franciosa M, Triadafilopoulos G, Mashimo H. Stretta Radiofrequency Treatment for GERD: A Safe and Effective Modality. Gastroenterol Res Pract 2013;2013:783815.

5. Lipka S, Kumar A, Richter JE. No Evidence for Efficacy of Radiofrequency Ablation for Treatment of Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2015;13:1058-1067 e1.

6. Noar M, Squires P, Noar E, et al. Long-term maintenance effect of radiofrequency energy delivery for refractory GERD: a decade later. Surg Endosc 2014;28:2323-33.

7.Hunter JG, Kahrilas PJ, Bell RC, et al. Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial. Gastroenterology 2015;148:324-333 e5.

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