Pyloric Therapy in Gastroparesis Botox and Beyond Nitin K. Ahuja, MD, MS She was admitted to the hospital shortly thereafter for symptom exacerbation, and an EGD with botulinum toxin injection (200 units in a four-quadrant distribution) was performed on an inpatient basis (Figure 1).
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50-year-old woman was referred to the neurogastroenterology and motility clinic with a chief complaint of nausea and vomiting, present and progressive for the past year. She had a history of well-controlled diabetes and multiple myeloma status post stem cell transplant. From a baseline weight of 300 pounds, she had lost 150 pounds over the prior year. A gastric emptying test performed a few months prior revealed approximately 80% meal retention at 4 hours. She had tried multiple medications without symptomatic benefit, including prokinetics (metoclopramide, prucalopride), antinauseants (ondansetron, promethazine, lorazepam, scopolamine, dronabinol), and neuromodulators (olanzapine, buspirone). Additionally, a history of QTc prolongation (550 msec) had made her provider team reluctant to consider other agents. At the end of our visit, a decision was made to pursue an EGD with pyloric botulinum toxin injection and, if unhelpful, consideration of an enteral feeding tube.
Figure 1. Pre-pyloric stomach above); pylorus s/p 200 unit botulinum toxin injection (below)
She was discharged tolerating an oral diet without difficulty. In clinic followup one month later, she reported significant and persistent symptom improvement and had gained back close to 20 pounds. In light of slowly
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recurrent symptoms, a repeat pyloric Botox injection was performed six months later, again with marked benefit. The therapeutic use of botulinum toxin in gastroparesis remains controversial. Its first published use at the pylorus was in 1998 (three years after the first report of botulinum toxin being successfully used at the lower esophageal sphincter in achalasia). Open-label case series of pyloric botulinum toxin injection have shown a substantial rates of symptom benefit, often just shy of 50%, though the effects are reliably temporary (usually on the order of months). Two small randomized controlled trials, however, showed no significant benefit of pyloric botulinum toxin injection for either gastroparesis symptoms or gastric emptying when compared to a saline placebo. On the basis of the RCT data, current society guidelines recommend against offering botulinum toxin as conventional gastroparesis therapy. The skeptic’s reading of these data, however, is that they may have been underpowered (n=32 in the larger of the two RCTs) to detect significant differences between study arms, particularly given that pyloric dysfunction likely affects only a minority of the gastroparesis population at large. Recognizing that gastric emptying delay elides a wide range of organ-specific pathology, including gastric dysrhythmia, impaired fundic accommodation, and sensory neuropathy, many gastroparesis patients are simply not predisposed to respond to botulinum toxin injection at a mechanistic level (Figure 2).
