Abstract
Case series report symptom reductions after pyloric botulinum toxin injection in gastroparesis, but small controlled trials show no benefit. Factors that enhance response to therapy are undefined. A retrospective analysis of 179 gastroparetics undergoing pyloric botulinum toxin injection from 2001 to 2007 assessed responses relating to drug dosing, demographic factors, comorbidities, and gastric function. Overall, there was a decrease in gastroparetic symptoms 1–4 months after pyloric botulinum toxin injection in 92 patients (51.4%). Increasing the botulinum toxin dose significantly improved clinical responses of patients who provided information on symptoms after therapy (100 units: 54.2%; 200 units: 76.7%; P = 0.02). Other factors that improved response to botulinum toxin included female gender, age <50 years, and nondiabetic nonpostsurgical etiology (all P < 0.05). Eighty-seven patients received 307 follow-up injections. A clinical response to a second injection was observed in 73.4% of evaluable patients. In conclusion, responses to pyloric botulinum toxin depended on dose and were maintained on repeat injection. Subgroup analyses defined subgroups likely to benefit. These findings provide the foundation for large, controlled trials of high-dose botulinum toxin in selected gastroparesis subsets.
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Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127:1592–1622. doi:10.1053/j.gastro.2004.09.055.
Soykan I, Sivri B, Saroseik I, Kiernan B, McCallum RW. Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis Sci. 1998;43:2398–2404. doi:10.1023/A:1026665728213.
Annese V, Janssens J, Vantrappen G, et al. Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination. Gastroenterology. 1992;102:823–828.
Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986;90:1919–1925.
Montecucco C, Schiavo G. Mechanism of action of tetanus and botulinum neurotoxins. Mol Microbiol. 1994;13:1–8. doi:10.1111/j.1365-2958.1994.tb00396.x.
Gupta P, Rao SS. Attenuation of isolated pyloric pressure waves in gastroparesis in response to botulinum toxin injection: a case report. Gastrointest Endosc. 2002;56:770–772. doi:10.1016/S0016-5107(02)70140-5.
Ezzeddine D, Jit R, Katz N, Gopalswamy N, Bhutani MS. Pyloric injection of botulinum toxin for treatment of diabetic gastroparesis. Gastrointest Endosc. 2002;55:920–923. doi:10.1067/mge.2002.124739.
Miller LS, Szych GA, Kantor SB, et al. Treatment of idiopathic gastroparesis with injection of botulinum toxin into the pyloric sphincter muscle. Am J Gastroenterol. 2002;97:1653–1660. doi:10.1111/j.1572-0241.2002.05823.x.
Lacy BE, Zayat EN, Crowell MD, Schuster MM. Botulinum toxin for the treatment of gastroparesis: a preliminary report. Am J Gastroenterol. 2002;97:1548–1552. doi:10.1111/j.1572-0241.2002.05741.x.
Lacy BE, Crowell MD, Schettler-Duncan A, Mathis C, Pasricha PJ. The treatment of diabetic gastroparesis with botulinum toxin injection of the pylorus. Diabetes Care. 2004;27:2341–2347. doi:10.2337/diacare.27.10.2341.
Arts J, Van Gool S, Caenepeel P, Verbeke K, Janssens J, Tack J. Influence of intrapyloric botulinum toxin injection of gastric emptying and meal-related symptoms in gastroparesis patients. Aliment Pharmacol Ther. 2006;24:661–667. doi:10.1111/j.1365-2036.2006.03019.x.
Wiesel PH, Schneider R, Dorta G, Blum AL, Gillet M, Michetti P. Botulinum toxin for refractory postoperative pyloric spasm. Endoscopy. 1997;29:132. doi:10.1055/s-2007-1004091.
Bromer MQ, Friedenberg F, Miller LS, Fisher RS, Swartz K, Parkman HP. Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis. Gastrointest Endosc. 2005;61:833–839. doi:10.1016/S0016-5107(05)00328-7.
Ben-Youssef R, Baron PW, Franco E, Walter MH, Lewis T, Ojogho O. Intrapyloric injection of botulinum toxin A for the treatment of persistent gastroparesis following successful pancreatic transplantation. Am J Transplant. 2006;6:214–218. doi:10.1111/j.1600-6143.2005.01153.x.
Kent MS, Pennathur A, Fabian T, et al. A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy. Surg Endosc. 2007;21:754–757. doi:10.1007/s00464-007-9225-9.
Friedenberg FK, Palit A, Parkman HP, Hanlon A, Nelson DB. Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol. 2008;103:416–423. doi:10.1111/j.1572-0241.2007.01676.x.
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.
Schiavo G, Shone CC, Rossetto O, Alexander FC, Montecucco C. Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin. J Biol Chem. 1993;268:11516–11519.
Hou YP, Zhang YP, Song YF, Zhu CM, Wang YC, Xie GL. Botulinum toxin type A inhibits rat pyloric myoelectrical activity and substance P release in vivo. Can J Physiol Pharmacol. 2007;85:209–214. doi:10.1139/Y07-018.
De Looze DA, Verdievel HG, Peeters TL, De Vos MM. The pyloric sphincter is back in town. Gastroenterology. 2000;118:A468. abstract.
Harris CP, Alderson K, Nebeker J, Holds JB, Anderson RL. Histologic features of human orbicularis oculi treated with botulinum A toxin. Arch Ophthalmol. 1991;109:393–395.
Bredenoord AJ, Chial HJ, Camilleri M, Mullan BP, Murray JA. Gastric accommodation and emptying in evaluation of patients with upper gastrointestinal symptoms. Clin Gastroenterol Hepatol. 2003;1:264–272. doi:10.1016/S1542-3565(03)00130-7.
Samsom M, Salet GA, Roelofs JM, Akkermans LM, Van Berge Henegouwen GP, Smout AJ. Compliance of the proximal stomach and dyspeptic symptoms in patients with type I diabetes mellitus. Dig Dis Sci. 1995;40:2037–2042. doi:10.1007/BF02208676.
Samsom M, Roelofs JM, Akkermans LM, Van Berge Henegouwen GP, Smout AJ. Proximal gastric motor activity in response to a liquid meal in type I diabetes mellitus with autonomic neuropathy. Dig Dis Sci. 1998;43:491–496. doi:10.1023/A:1018894520557.
Camilleri M, Malagelada JR. Abnormal intestinal motility in diabetics with the gastroparesis syndrome. Eur J Clin Invest. 1984;14:420–427. doi:10.1111/j.1365-2362.1984.tb01206.x.
Bizer E, Harrell S, Koopman J, Hatfield C, Cacchione R, Wo JM. Obesity is common in gastroparesis despite nausea, vomiting, and early satiety. Gastroenterology. 2005;128:M1895. abstract.
Jankovic J. Botulinum toxin in movement disorders. Curr Opin Neurol. 1994;7:358–366.
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Dr. Hasler receives grant funding from the NIH (1 U01 DK073985-01) to support his research in gastroparesis.
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Coleski, R., Anderson, M.A. & Hasler, W.L. Factors Associated with Symptom Response to Pyloric Injection of Botulinum Toxin in a Large Series of Gastroparesis Patients. Dig Dis Sci 54, 2634–2642 (2009). https://doi.org/10.1007/s10620-008-0660-9
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DOI: https://doi.org/10.1007/s10620-008-0660-9