This is half of a two-part debate — read the opposing argument. The opinions expressed here are that of the author and do not represent the position of AGA.
Despite what the title of this commentary may suggest, I want to state at the onset that I am not a Luddite. I trained in therapeutic endoscopy and have embraced new technology throughout my career. Nothing would please me more than a relatively simple endoscopic solution for a complicated problem such as gastroparesis. So, the question is: Does gastric peroral endoscopic pyloromyotomy (G-POEM) represent that “magic bullet” we’ve all been waiting for?
Let’s begin with the rationale for this procedure. Pyloric dysfunction can certainly be associated with gastroparesis, and it is reasonable to hypothesize that this results in impaired gastric emptying. Advocates of G-POEM have taken this argument to its logical conclusion: Decreasing pyloric resistance should improve gastric emptying and, hence, clinical benefit. Setting aside the fact that a delay in gastric emptying does not necessarily correlate with symptom severity, let us examine the clinical experience with therapies based on pyloric intervention, beginning with botulinum toxin. Initial reports generated much enthusiasm, with success rates as high as 90 percent — reminiscent of the current buzz about G-POEM — but two randomized trials failed to show any improvement in symptoms in the active treatment group.1,2 It has been argued that this was due to the small numbers of patients, lack of selectivity or technical factors related to the injection itself. What is not widely recognized is that gastric emptying did improve after botulinum toxin injection in at least one of these controlled studies, indicating that the treatment was effective in producing the desired physiologic outcome without a change in symptoms.
Advocates of G-POEM propose, with some merit, that a much greater reduction of pyloric resistance is needed to affect clinical outcomes. Let us therefore examine the historic experience with patients undergoing truncal vagotomy for peptic ulcer disease for whom the procedure was combined with surgical pyloroplasty to prevent symptoms from the expected delay in gastric emptying. In many ways, this is an ideal “experiment” to analyze — loss of vagal function to the stomach is expected to produce similar pathophysiologic changes as in other forms of gastroparesis (indeed, vagal neuropathy is considered to be a possible etiologic factor in these conditions). So, does pyloroplasty actually ameliorate symptoms of gastroparesis in patients undergoing truncal vagotomy? One prospective trial randomized nearly 250 patients to truncal vagotomy and pyloroplasty, selective vagotomy with pyloroplasty and parietal cell vagotomy alone, and the researchers followed them for more than 10 years.3 Between 50 and 70 percent of patients with pyloroplasty developed dyspeptic symptoms (pain, heartburn, nausea and vomiting). In these patients, dumping (about 30 to 40 percent) and diarrhea (about 35 to 50 percent) were common, although it was usually described as mild or intermittent. One could therefore conclude that rendering the pylorus wide open does not ameliorate symptoms in a “surgical model” of gastroparesis and may have adverse events.
Which brings us to G-POEM — to date, nearly half a dozen studies have been undertaken, with all of them being open-label, having small numbers of heterogeneous patients, varying metrics and no long-term follow-up periods. Nevertheless, at least two of these studies are reasonably comparable but with results that are somewhat incongruous. In a study of 16 patients, Dacha et al showed dramatic improvements in overall Gastroparesis Cardinal Symptom Index (GCSI; measured on a scale of zero to five) score, which decreased from 3.4 to 1.5.4 However, a much larger study (47 patients) from the Cleveland Clinic showed a much less robust improvement: the change in GCSI only went from 4.6 to 3.3.5 Hopefully, a truer picture will emerge if and when controlled studies are performed. But, at least one question to ask is: If G-POEM is simply pyloroplasty by a different route, then why should the results be different than open pyloroplasty performed by experienced surgeons?
This is a good segue to the final and more philosophical part of this commentary. First, I want to commend endoscopists and surgeons for wading into this area — we need all the help we can get! However, some rules must be followed. Importantly, let us all acknowledge that G-POEM as a procedure is not standardized, no training requirement or credentialing is in place regarding how to perform it, and we have no data on long-term outcomes. With only 100 or so cases described in the medical literature and no consensus on outcomes, G-POEM is unarguably an experimental procedure with the potential to permanently alter gastric anatomy with unknown consequences. This should be made explicitly clear to the patient, of course, but it also means that G-POEM should be performed only after approvals have been received from an institutional review board and an independent safety board has been established to monitor safety and outcomes.
With only 100 or so cases described in the medical literature and no consensus on outcomes, G-POEM is unarguably an experimental procedure with the potential to permanently alter gastric anatomy with unknown consequences.
Beware of tempting but possibly false analogies: Just because achalasia responds to a sphincteric intervention does not mean that gastroparesis will, too. However, if you are convinced about the merits of this approach based on your understanding of the disease process, then show your commitment to the patient by continuing to take care of him or her if the procedure fails (the old adage of “if you break it, you own it”).
Respect the power of controlled trials. I have already discussed botulinum toxin injections into the pylorus and how this continues to be practiced despite scientific evidence to the contrary. Another similar example is illustrated by the practice of endoscopic sphincterotomy for the so-called syndrome of sphincter of Oddi dysfunction. For decades, patients with unexplained pain were having their biliary (and often pancreatic) sphincters excised by experts claiming response rates of 60 to 80 percent. Thousands of patients underwent this procedure, many of whom developed acute pancreatitis. It took the landmark EPISOD trial to show that sphincterotomy not only had no benefit in these patients but that it actually led to worse outcomes.6 Yet the practice continues in many parts of the country, and patients are still being told that this is a viable and beneficial approach to their pain.
I have no doubt that motility specialists and their interventional colleagues are highly motivated to help patients with a disorder for which current treatment options are very limited. However, we must resist the temptation — no matter how well intentioned — to do the wrong thing for the right reason. Let us not jump on the same bus that has taken us down dead-end streets before (sphincterotomy for sphincter of Oddi dysfunction, pancreatectomy for minimal-change pancreatitis and botulinum toxin for gastroparesis) with patients paying the costs for us clinicians to “learn.” G-POEM is a promising procedure, but it must be rigorously tested in randomized controlled trials before we can offer it to patients outside of a research setting. Until then, here’s to hoping!
- G-POEM is a new way to perform pyloromyotomy in patients with gastroparesis with the rationale that functional pyloric obstruction is the root cause of the pathophysiology and symptoms.
- As with most open label interventions in motility disorders, short-term results in very small numbers of patients are generally promising.
- Much more needs to be learned about the efficacy and safety of the procedure particularly beyond a few months as well as who the appropriate candidate is.
- Until then, G-POEM should be considered experimental and done under a research protocol.
Dr. Pasricha has no conflicts to disclose.
1. Arts, J., Holvoet, L., Caenepeel P., et al, Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis. Aliment Pharmacol Ther. 2007;26:1251-1258.
2. Friedenberg, F.K., Palit, A., Parkman, H.P., Hanlon, A., Nelson, D.B. Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol. 2008;103:416-423.
3. Hoffmann, J., Jensen, H.E., Christiansen, J., Olesen, A., Loud, F.B., Hauch, O. Prospective controlled vagotomy trial for duodenal ulcer. Results after 11-15 years. Ann Surg. 1989;209:40-45.
4. Dacha, S., Mekaroonkamol, P., Li, L., et al, Outcomes and quality-of-life assessment after gastric per-oral endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017;86:282-289.
5. Rodriguez, J.H., Haskins, I.N., Strong, A.T., et al, Per oral endoscopic pyloromyotomy for refractory gastroparesis: initial results from a single institution. Surg Endosc. 2017;31:5381-5388.
6. Cotton, P.B., Pauls, Q., Keith, J., et al, The EPISOD study: long-term outcomes. Gastrointest Endosc. 2018;87:205-210.