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Pathophysiology, Aetiology and Treatment of Gastroparesis

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Abstract

Gastroparesis is characterized by delayed gastric emptying, with symptoms such as nausea, vomiting and abdominal pain, in the absence of mechanical obstruction. In most cases, it is idiopathic although diabetes mellitus is another leading cause. The physiology of gastric emptying is a complex process which is influenced by various inputs including the central nervous system, enteric nervous system and gut hormones. Developments in our understanding of gastroparesis have now demonstrated dysfunction in these systems, thus disrupting normal gastric emptying. Once mechanical obstruction is excluded, gastric scintigraphy remains the gold standard for diagnosis although wireless motility capsule and breath testing are alternative methods for diagnosis. Treatment for gastroparesis is challenging, and widely available therapies are often limited either by their poor evidence for efficacy or concerns over their long-term safety profile. Novel prokinetic agents have shown initial promise in clinical trials, and new endoscopic techniques such as gastric per-oral endoscopic myotomy are emerging. These new treatment modalities may provide an option in refractory gastroparesis with the adage of reduced morbidity compared to surgical treatments.

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References

  1. Parkman HP, Hallinan EK, Hasler WL, Farrugia G, Koch KL, Calles J, et al. Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis. Neurogastroenterol Motil. 2016.

  2. Hasler WL, Wilson LA, Parkman HP, Koch KL, Abell TL, Nguyen L, et al. Factors related to abdominal pain in gastroparesis: Contrast to patients with predominant nausea and vomiting. Neurogastroenterol Motil. 2013.

  3. Rey E, Choung RS, Schleck CD, Zinsmeister AR, Talley NJ, Locke GR. Prevalence of hidden gastroparesis in the community: The gastroparesis “iceberg.” J Neurogastroenterol Motil. 2012.

  4. Soykan I, Sivri B, Sarosiek 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 [Internet]. 1998 Nov [cited 2019 Jul 19];43(11):2398–404. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9824125.

  5. Talley NJ, Young L, Bytzer P, Hammer J, Leemon M, Jones M, et al. Impact of chronic gastrointestinal symptoms in diabetes mellitus on health-related quality of life. Am J Gastroenterol. 2001.

  6. Abrahamsson H, Jansson G. Elicitation of Reflex Vagal Relaxation of the Stomach from Pharynx and Esophagus in the Cat. Acta Physiol Scand. 1969.

  7. Hinder RA, Kelly KA. Human gastric pacesetter potential. Site of origin, spread, and response to gastric transection and proximal gastric vagotomy. Am J Surg. 1977.

  8. Carlson HC, Code CF, Nelson RA. Motor action of the canine gastroduodenal junction: a cineradiographic, pressure, and electric study. Am J Dig Dis [Internet]. 1966 Feb [cited 2019 Jul 19];11(2):155–72. http://www.ncbi.nlm.nih.gov/pubmed/5904357.

  9. Meyer JH, Thomson JB, Cohen MB, Shadchehr A, Mandiola SA. Sieving of solid food by the canine stomach and sieving after gastric surgery. Gastroenterology [Internet]. 1979 Apr [cited 2019 Jul 19];76(4):804–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/422008.

  10. Code CF, Marlett JA. The interdigestive myo-electric complex of the stomach and small bowel of dogs. J Physiol [Internet]. 1975 Mar [cited 2019 Jul 19];246(2):289–309. http://www.ncbi.nlm.nih.gov/pubmed/1142245.

  11. Telford GL, Sarna SK. The migrating myoelectric complex of the small intestine. Chaos [Internet]. 1991 Oct [cited 2019 Jul 19];1(3):299–302. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12779928.

  12. Costa M. Anatomy and physiology of the enteric nervous system. Gut. 2000.

  13. Varón AR, Zuleta J. From the physiology of gastric emptying to the understanding of gastroparesis. Rev Colomb Gastroenterol. 2010.

  14. Cannon WB. Peristalsis, segmentation, and the myenteric reflex. Am J Physiol Content. 1912.

  15. Furness JB. The enteric nervous system (Google eBook). 2006.

  16. Browning KN, Travagli RA. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol. 2014.

  17. Rogers RC, Hermann GE, Travagli RA. Brainstem pathways responsible for oesophageal control of gastric motility and tone in the rat. J Physiol. 1999.

  18. Luiking YC, Akkermans LMA, Peeters TL, Cnossen PJ, Nieuwenhuijs VB, Vanberge -Henegouwen GP. Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors. Neurogastroenterol Motil [Internet]. 2002 Apr [cited 2019 Jul 19];14(2):151–9. http://www.ncbi.nlm.nih.gov/pubmed/11975715.

  19. Hagemann D, Meier JJ, Gallwitz B, Schmidt WE. [Appetite regulation by ghrelin - a novel neuro-endocrine gastric peptide hormone in the gut-brain-axis]. Z Gastroenterol [Internet]. 2003 Sep [cited 2019 Jul 19];41(9):929–36. Available from: http://www.ncbi.nlm.nih.gov/pubmed/13130331.

  20. Jeon TY, Lee S, Kim HH, Kim YJ, Son HC, Kim DH, et al. Changes in plasma ghrelin concentration immediately after gastrectomy in patients with early gastric cancer. J Clin Endocrinol Metab. 2004.

  21. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002.

  22. Giralt M, Vergara P. Glucagonlike peptide-1 (GLP-1) participation in ileal brake induced by intraluminal peptones in rat. Dig Dis Sci [Internet]. 1999 Feb [cited 2019 Jul 19];44(2):322–9. http://www.ncbi.nlm.nih.gov/pubmed/10063918.

  23. Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N. Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB. Physiol Rev [Internet]. 2017 [cited 2019 Jul 19];97(1):411–63. http://www.ncbi.nlm.nih.gov/pubmed/28003328.

  24. Matzinger D, Degen L, Drewe J, Meuli J, Duebendorfer R, Ruckstuhl N, et al. The role of long chain fatty acids in regulating food intake and cholecystokinin release in humans. Gut [Internet]. 2000 May [cited 2019 Jul 19];46(5):688–93. http://www.ncbi.nlm.nih.gov/pubmed/10764713.

  25. Prosapio JG, Jialal I. Physiology. StatPearls: Gastrin; 2019.

    Google Scholar 

  26. Grover M, Farrugia G, Lurken MS, Bernard CE, Faussonepellegrini MS, Smyrk TC, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011.

  27. Sanders KM, Koh SD, Ward SM. Interstitial cells of cajal as pacemakers in the gastrointestinal tract. Annu Rev Physiol. 2006.

  28. Grover M, Bernard CE, Pasricha PJ, Lurken MS, Faussone-Pellegrini MS, Smyrk TC, et al. Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium. Neurogastroenterol Motil [Internet]. 2012 Jun [cited 2019 Jul 19];24(6):531–9, e249. http://www.ncbi.nlm.nih.gov/pubmed/22339929.

  29. Stevens JE, Jones KL, Rayner CK, Horowitz M. Pathophysiology and pharmacotherapy of gastroparesis: current and future perspectives. Expert Opin Pharmacother [Internet]. 2013 Jun [cited 2019 Jul 19];14(9):1171–86. http://www.ncbi.nlm.nih.gov/pubmed/23663133.

  30. Koch KL, Calles-Escandón J. Diabetic gastroparesis. Gastroenterol Clin North Am [Internet]. 2015 Mar [cited 2019 Jul 19];44(1):39–57. http://www.ncbi.nlm.nih.gov/pubmed/25667022.

  31. Gangula PRR, Sekhar KR, Mukhopadhyay S. Gender bias in gastroparesis: Is nitric oxide the answer? Digest Dis Sci.. 2011.

  32. Watkins CC, Sawa A, Jaffrey S, Blackshaw S, Barrow RK, Snyder SH, et al. Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy. J Clin Invest. 2000.

  33. Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology [Internet]. 1986 Jun [cited 2019 Jul 19];90(6):1919–25. http://www.ncbi.nlm.nih.gov/pubmed/3699409.

  34. Talley NJ, Verlinden M, Jones M. Can symptoms discriminate among those with delayed or normal gastric emptying in dysmotility-like dyspepsia? Am J Gastroenterol. 2001.

  35. Karamanolis G, Caenepeel P, Arts J, Tack J. Determinants of symptom pattern in idiopathic severely delayed gastric emptying: Gastric emptying rate or proximal stomach dysfunction? Gut. 2007.

  36. Kumar A, Attaluri A, Hashmi S, Schulze KS, Rao SSC. Visceral hypersensitivity and impaired accommodation in refractory diabetic gastroparesis. Neurogastroenterol Motil. 2008.

  37. Barnett JL, Owyang C. Serum glucose concentration as a modulator of interdigestive gastric motility. Gastroenterology. 1988.

  38. Iwasaki H, Kajimura M, Osawa S, Kanaoka S, Furuta T, Ikuma M, et al. A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus. J Gastroenterol [Internet]. 2006 Nov [cited 2019 Jul 19];41(11):1076–87. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17160518.

  39. Sandroni P, Opfer-Gehrking TL, McPhee BR, Low PA. Postural tachycardia syndrome: Clinical features and follow-up study. Mayo Clin Proc. 1999.

  40. Park KJ, Singer W, Sletten DM, Low PA, Bharucha AE. Gastric emptying in postural tachycardia syndrome: A preliminary report. Clin Auton Res. 2013.

  41. Edwards LL, Pfeiffer RF, Quigley EM, Hofman R, Balluff M. Gastrointestinal symptoms in Parkinson’s disease. Mov Disord [Internet]. 1991 [cited 2019 Jul 19];6:151–6. http://www.ncbi.nlm.nih.gov/pubmed/2057006.

  42. Singaram C, Ashraf W, Gaumnitz EA, Torbey C, Sengupta A, Pfeiffer R, et al. Dopaminergic defect of enteric nervous system in Parkinson’s disease patients with chronic constipation. Lancet (London, England) [Internet]. 1995 Sep 30 [cited 2019 Jul 19];346:861–4. http://www.ncbi.nlm.nih.gov/pubmed/7564669.

  43. Djaldetti R, Baron J, Ziv I, Melamed E. Gastric emptying in Parkinson’s disease: Patients with and without response fluctuations. Neurology. 1996.

  44. Nimmo W, Heading R, Wilson J, Tothill P, Prescott L. Inhibition of gastric emptying and drug absorption by narcotic analgesics. Br J Clin Pharmacol. 1975.

  45. Murphy DB, Sutton JA, Prescott LF, Murphy MB. Opioid-induced delay in gastric emptying: a peripheral mechanism in humans. Anesthesiology [Internet]. 1997 Oct [cited 2019 Jul 19];87:765–70. http://www.ncbi.nlm.nih.gov/pubmed/9357876.

  46. Lock G, Holstege A, Lang B, Schölmerich J. Gastrointestinal manifestations of progressive systemic sclerosis. Am J Gastroenterol. 1997.

  47. Manetti M, Milia AF, Benelli G, Messerini L, Matucci-Cerinic M, Ibba-Manneschi L. The gastric wall in systemic sclerosis patients: A morphological study. Ital J Anat Embryol. 2010.

  48. Nelson AD, Mouchli MA, Valentin N, Deyle D, Pichurin P, Acosta A, et al. Ehlers Danlos syndrome and gastrointestinal manifestations: A 20-year experience at Mayo Clinic. Neurogastroenterol Motil. 2015.

  49. Vella A, Lee JS, Camilleri M, Szarka LA, Burton DD, Zinsmeister AR, et al. Effects of pramlintide, an amylin analogue, on gastric emptying in type 1 and 2 diabetes mellitus. Neurogastroenterol Motil [Internet]. 2002 Apr [cited 2019 Jul 19];14:123–31. http://www.ncbi.nlm.nih.gov/pubmed/11975712.

  50. Cervera A, Wajcberg E, Sriwijitkamol A, Fernandez M, Zuo P, Triplitt C, et al. Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes. Am J Physiol Endocrinol Metab [Internet]. 2008 May [cited 2019 Jul 19];294:E846-52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18334612.

  51. Maes BD, Vanwalleghem J, Kuypers D, Ghoos Y, Rutgeerts PJ, Vanrenterghem YF. Differences in gastric motor activity in renal transplant recipients treated with FK-506 versus cyclosporine. Transplantation [Internet]. 1999 Nov 27 [cited 2019 Jul 19];68:1482–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10589943.

  52. Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. Clinical guideline: Management of gastroparesis. Am J Gastroenterol. 2013.

  53. Reddymasu S, Olyaee M. Gastroparesis. BMJ Best Pract. 2018.

  54. Reddivari AKR, Mehta P. Gastroparesis [Internet]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019. https://www.ncbi.nlm.nih.gov/books/NBK551528/.

  55. Abell TL, Camilleri M, Donohoe K, Hasler WL, Lin HC, Maurer AH, et al. Consensus recommendations for gastric emptying scintigraphy: A joint report of the American neurogastroenterology and motility society and the society of nuclear medicine. Am J Gastroenterol. 2008.

  56. Tougas G, Chen Y, Coates G, Paterson W, Dallaire C, Paré P, et al. Standardization of a simplified scintigraphic methodology for the assessment of gastric emptying in a multicenter setting. Am J Gastroenterol. 2000.

  57. Sachdeva P, Malhotra N, Pathikonda M, Khayyam U, Fisher RS, Maurer AH, et al. Gastric emptying of solids and liquids for evaluation for gastroparesis. Dig Dis Sci. 2011.

  58. Ziessman HA, Chander A, Clarke JO, Ramos A, L.Wahl R. The Added Diagnostic Value of Liquid Gastric Emptying Compared with Solid Emptying Alone. J Nucl Med. 2009.

  59. Shin AS, Camilleri M. Diagnostic Assessment of Diabetic Gastroparesis. Diabetes. 2013.

  60. Camilleri M, Iturrino J, Bharucha AE, Burton D, Shin A, Jeong ID, et al. Performance characteristics of scintigraphic measurement of gastric emptying of solids in healthy participants. Neurogastroenterol Motil. 2012.

  61. Farmer AD, Scott SM, Hobson AR. Gastrointestinal motility revisited: The wireless motility capsule. United Eur Gastroenterol J. 2013.

  62. Camilleri M, Bharucha AE, Di Lorenzo C, Hasler WL, Prather CM, Rao SS, et al. American neurogastroenterology and motility society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice. Neurogastroenterol Motil. 2008.

  63. Kuo B, McCallum RW, Koch KL, Sitrin MD, Wo JM, Chey WD, et al. Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects. Aliment Pharmacol Ther. 2008.

  64. Stein E, Berger Z, Hutfless S, Shah L, Wilson L, Haberl E, et al. Wireless motility capsule versus other diagnostic technologies for evaluating gastroparesis and constipation: a comparative effectiveness review. Comp Eff Rev. 2013.

  65. Kloetzer L, Chey WD, McCallum RW, Koch KL, Wo JM, Sitrin M, et al. Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule. Neurogastroenterol Motil. 2010.

  66. Cassilly D, Kantor S, Knight LC, Maurer AH, Fisher RS, Semler J, et al. Gastric emptying of a non-digestible solid: Assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy. Neurogastroenterol Motil. 2008.

  67. National Institute for Health and Care Excellence. Assessing motility of the gastrointestinal tract using a wireless capsule Interventional procedures guidance [IPG502]. 2014.

  68. Ghoos YF, Maes BD, Geypens BJ, Mys G, Hiele MI, Rutgeerts PJ, et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. Gastroenterology. 1993.

  69. Lee JS, Camilleri M, Zinsmeister AR, Burton DD, Choi MG, Nair KS, et al. Toward office-based measurement of gastric emptying in symptomatic diabetes diabetics using [13C]octanoic acid breath test. Am J Gastroenterol. 2000.

  70. Choi MG, Camilleri M, Burton DD, Zinsmeister AR, Forstrom LA, Sreekumaran Nair K. Reproducibility and simplification of 13C-octanoic acid breath test for gastric emptying of solids. Am J Gastroenterol. 1998.

  71. Van Nieuwenhoven MA, Wagenmakers AJM, Senden JMG, Brouns F, Brummer RJM. Performance of the [13C]-acetate gastric emptying breath test during physical exercise. Eur J Clin Invest. 1999.

  72. Bharucha AE, Camilleri M, Veil E, Burton D, Zinsmeister AR. Comprehensive assessment of gastric emptying with a stable isotope breath test. Neurogastroenterol Motil. 2013.

  73. Szarka LA, Camilleri M, Vella A, Burton D, Baxter K, Simonson J, et al. A Stable Isotope Breath Test With a Standard Meal for Abnormal Gastric Emptying of Solids in the Clinic and in Research. Clin Gastroenterol Hepatol. 2008.

  74. Van De Casteele M, Luypaerts A, Geypens B, Fevery J, Ghoos Y, Nevens F. Oxidative breakdown of octanoic acid is maintained in patients with cirrhosis despite advanced disease. Neurogastroenterol Motil. 2003.

  75. Verbeke K. Will the 13C-octanoic acid breath test ever replace scintigraphy as the gold standard to assess gastric emptying? Neurogastroenterol Motil. 2009.

  76. Fidler J, Bharucha AE, Camilleri M, Camp J, Burton D, Grimm R, et al. Application of magnetic resonance imaging to measure fasting and postprandial volumes in humans. Neurogastroenterol Motil. 2009.

  77. Muresan C, Blaga TS, Muresan L, Dumitrascu DL. Abdominal ultrasound for the evaluation of gastric emptying revisited. J Gastrointest Liver Dis. 2015.

  78. Homko CJ, Duffy F, Friedenberg FK, Boden G, Parkman HP. Effect of dietary fat and food consistency on gastroparesis symptoms in patients with gastroparesis. Neurogastroenterol Motil. 2015.

  79. Ray TK, Mansell KM, Knight LC, Malmud LS, Owen OE, Boden G. Long-term effects of dietary fiber on glucose tolerance and gastric emptying in noninsulin-dependent diabetic patients. Am J Clin Nutr. 1983.

  80. Wytiaz V, Homko C, Duffy F, Schey R, Parkman HP. Foods Provoking and Alleviating Symptoms in Gastroparesis: Patient Experiences. Dig Dis Sci. 2015.

  81. Bujanda L. The effects of alcohol consumption upon the gastrointestinal tract. Am J Gastroenterol. 2000.

  82. Sanaka M, Anjiki H, Tsutsumi H, Abe K, Kawakami T, Saitoh M, et al. Effect of cigarette smoking on gastric emptying of solids in Japanese smokers: A crossover study using the 13C-octanoic acid breath test. J Gastroenterol. 2005.

  83. Samsom M, Akkermans LMA, Jebbink RJA, Van Isselt H, VanBerge-Henegouwen GP, Smout AJPM. Gastrointestinal motor mechanisms in hyperglycaemia induced delayed gastric emptying in type I diabetes mellitus. Gut. 1997.

  84. MacGregor IL, Gueller R, Watts HD, Meyer JH. The Effect of Acute Hyperglycemia on Gastric Emptying in Man. Gastroenterology. 1976.

  85. Schvarcz E, Palmer M, Aman J, Horowitz M, Stridsberg M, Berne C. Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin-dependent diabetes mellitus. Gastroenterology. 1997.

  86. Halland M, Bharucha AE. Relationship Between Control of Glycemia and Gastric Emptying Disturbances in Diabetes Mellitus. Clin Gastroenterol Hepatol. 2016.

  87. Bharucha AE, Kudva Y, Basu A, Camilleri M, Low PA, Vella A, et al. Relationship between glycemic control and gastric emptying in poorly controlled type 2 diabetes. Clin Gastroenterol Hepatol. 2015.

  88. Izzy M, Lee M, Johns-Keating K, Kargoli F, Beckoff S, Chun K, et al. Glycosylated hemoglobin level may predict the severity of gastroparesis in diabetic patients. Diabetes Res Clin Pract. 2018.

  89. Bharucha AE, Batey-Schaefer B, Cleary PA, Murray JA, Cowie C, Lorenzi G, et al. Delayed gastric emptying is associated with early and long-term hyperglycemia in type 1 diabetes mellitus. Gastroenterology. 2015.

  90. Parrish CR. Nutritional considerations in the patient with gastroparesis. Gastroenterol Clin North Am. 2015.

  91. Parkman HP, Yates KP, Hasler WL, Nguyan L, Pasricha PJ, Snape WJ, et al. Dietary intake and nutritional deficiencies in patients with diabetic or idiopathic gastroparesis. Gastroenterology. 2011.

  92. Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004.

  93. Pearce CB, Duncan HD. Enteral feeding. Nasogastric, nasojejunal, percutaneous endoscopic gastrostomy, or jejunostomy: Its indications and limitations. Postgrad Med J. 2002.

  94. Fontana RJ, Barnett JL. Jejunostomy tube placement in refractory diabetic gastroparesis: a retrospective review. Am J Gastroenterol. 1996.

  95. Woodhouse S, Hebbard G, Knowles SR. Psychological controversies in gastroparesis: A systematic review. World J Gastroenterol. 2017.

  96. Ljótsson B, Hedman E, Andersson E, et al. Internet-delivered exposure-based treatment vs. Stress management for irritable bowel syndrome: A randomized trial. Am J Gastroenterol. 2011.

  97. Ljótsson B, Hesser H, Andersson E, Lackner JM, El Alaoui S, Falk L, et al. Provoking symptoms to relieve symptoms: A randomized controlled dismantling study of exposure therapy in irritable bowel syndrome. Behav Res Ther. 2014.

  98. Andersson E, Ljátsson B, Smit F, Paxling B, Hedman E, Lindefors N, et al. Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: Results from a randomized controlled trial. BMC Public Health. 2011.

  99. Liu Y, Song X, Zhang Y, Zhou L, Ni R. The effects of comprehensive mental intervention on the recovery time of patients with postsurgical gastroparesis syndrome. J Clin Nurs. 2014.

  100. Snape WJ, Battle WM, Schwartz SS, Braunstein SN, Goldstein HA, Alavi A. Metoclopramide to treat gastroparesis due to diabetes mellitus. A double-blind, controlled trial. Ann Intern Med. 1982.

  101. Perkel MS, Moore C, Hersh T, Davidson ED. Metoclopramide therapy in patients with delayed gastric emptying - A randomized, double-blind study. Dig Dis Sci. 1979.

  102. McCallum RW, Ricci DA, Rakatansky H, Behar J, Rhodes JB, Salen G, et al. A multicenter placebo-controlled clinical trial of oral metoclopramide in diabetic gastroparesis. Diabetes Care. 1983.

  103. Ricci DA, Saltzman MB, Meyer C, Callachan C, McCallum RW. Effect of metoclopramide in diabetic gastroparesis. J Clin Gastroenterol. 1985.

  104. Rao AS, Camilleri M. Review article: Metoclopramide and tardive dyskinesia. Alimentary Pharmacology and Therapeutics. 2010.

  105. Parkman HP, Carlson MR, Gonyer D. Metoclopramide nasal spray is effective in symptoms of gastroparesis in diabetics compared to conventional oral tablet. Neurogastroenterol Motil. 2014.

  106. ANI Pharmaceuticals. Reglan tablets - Medication Guide [Internet]. Baudette; 2011. https://www.fda.gov/media/79804/download.

  107. European Medicines Agency. European Medicines Agency recommends changes to the use of metoclopramide. 2013.

  108. Braun A. Domperidone in the treatment of symptoms of delayed gastric emptying in diabetic patients. Adv Ther.. 1989;6:51–62.

    Google Scholar 

  109. Patterson D, Abell T, Rothstein R, Koch K, Barnett J. A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis. Am J Gastroenterol. 1999.

  110. Silvers D, Kipnes M, Broadstone V, Patterson D, Quigley EMM, McCallum R, et al. Domperidone in the management of symptoms of diabetic gastroparesis: Efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. Clin Ther. 1998.

  111. Soykan I, Sarosiek I, McCallum RW. The effect of chronic oral domperidone therapy on gastrointestinal symptoms, gastric emptying, and quality of life in patients with gastroparesis. Am J Gastroenterol. 1997.

  112. Kozarek R. Domperidone for symptomatic management of diabetic gastroparesis in metoclopramide treatment failures. Adv Ther. 1990.

  113. Medicines and Healthcare products Regulatory Agency. Domperidone: risks of cardiac side effects. Drug Saf Updat. 2014;7(10).

  114. European Medicines Agency. Restrictions on the use of domperidone-containing medicines. London; 2014.

  115. Acosta A, Camilleri M. Prokinetics in gastroparesis. Gastroenterology Clinics of North America. 2015.

  116. Maganti K, Onyemere K, Jones MP. Oral erythromycin and symptomatic relief of gastroparesis: A systematic review. Am J Gastroenterol. 2003.

  117. Janssens J, Peeters TL, Vantrappen G, Tack J, Urbain JL, De Roo M, et al. Improvement of Gastric Emptying in Diabetic Gastroparesis by Erythromycin. N Engl J Med. 2010.

  118. Bortolotti M, Mari C, Brunelli F, Sarti P, Miglioli M. Effect of intravenous clarithromycin on interdigestive gastroduodenal motility of patients with functional dyspepsia and Helicobacter pylori gastritis. Dig Dis Sci. 1999.

  119. Larson JM, Tavakkoli A, Drane WE, Toskes PP, Moshiree B. Advantages of Azithromycin Over Erythromycin in Improving the Gastric Emptying Half-Time in Adult Patients With Gastroparesis. J Neurogastroenterol Motil. 2010.

  120. Tack J, Depoortere I, Bisschops R, Delporte C, Coulie B, Meulemans A, et al. Influence of ghrelin on interdigestive gastrointestinal motility in humans. Gut. 2006.

  121. Dass NB, Munonyara M, Bassil AK, Hervieu GJ, Osbourne S, Corcoran S, et al. Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin. Neuroscience. 2003.

  122. Trudel L, Tomasetto C, Rio MC, Bouin M, Plourde V, Eberling P, et al. Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat. Am J Physiol Liver Physiol. 2015.

  123. Camilleri M, McCallum RW, Tack J, Spence SC, Gottesdiener K, Fiedorek FT. Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study. Gastroenterology. 2017.

  124. Lembo A, Camilleri M, McCallum R, Sastre R, Breton C, Spence S, et al. Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults With Diabetic Gastroparesis. Gastroenterology. 2016.

  125. Shin A, Camilleri M, Busciglio I, Burton D, Smith SA, Vella A, et al. The Ghrelin agonist rm-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus. Clin Gastroenterol Hepatol. 2013.

  126. Ejskjaer N, Dimcevski G, Wo J, Hellström PM, Gormsen LC, Sarosiek I, et al. Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: A randomized, placebo-controlled study. Neurogastroenterol Motil. 2010.

  127. Ejskjaer N, Vestergaard ET, HellstrÖm PM, Gormsen LC, Madsbad S, Madsen JL, et al. Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Aliment Pharmacol Ther. 2009.

  128. Ejskjaer N, Wo JM, Esfandyari T, Mazen Jamal M, Dimcevski G, Tarnow L, et al. A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil. 2013.

  129. Mccallum RW, Lembo A, Esfandyari T, Bhandari BR, Ejskjaer N, Cosentino C, et al. Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil. 2013.

  130. Ahn A, Barnes C, Shaywitz D, Grimaldi M, Canafax DM. Su1426 Velusetrag Improves Gastric Emptying Time in Subjects With Diabetic or Idiopathic Gastroparesis. Gastroenterology. 2015.

  131. Theravance Biopharma. Theravance Biopharma Announces Positive Top-Line Results from Phase 2b Study of Velusetrag (TD-5108) in Patients with Gastroparesis. 2017.

  132. Carbone F, Van Den Houte K, Clevers E, Andrews CN, Papathanasopoulos A, Holvoet L, et al. Prucalopride in Gastroparesis: A Randomized Placebo-Controlled Crossover Study. Am J Gastroenterol. 2019.

  133. Kumar M, Chapman A, Javed S, Alam U, Malik RA, Azmi S. The Investigation and Treatment of Diabetic Gastroparesis. Clinical Therapeutics. 2018.

  134. Stapleton J, Wo JM. Current Treatment of Nausea and Vomiting Associated with Gastroparesis: Antiemetics, Prokinetics, Tricyclics. Gastrointest Endosc Clin North Am. 2009.

  135. Pasricha PJ, Nguyen LAB, Snape WJ, Colvin R, Lee LA, Abell TL, et al. Changes in quality of life and symptoms in a large cohort of patients with gastroparesis followed prospectively for 48 weeks. Gastroenterology. 2010.

  136. Prakash C, Lustman PJ, Freedland KE, Clouse RE. Tricyclic antidepressants for functional nausea and vomiting: Clinical outcome in 37 patients. Dig Dis Sci. 1998.

  137. Sawhney MS, Prakash C, Lustman PJ, Clouse RE. Tricyclic antidepressants for chronic vomiting in diabetic patients. Dig Dis Sci. 2007.

  138. Parkman HP, Van Natta ML, Abell TL, McCallum RW, Sarosiek I, Nguyen L, et al. Effect of nortriptyline on symptoms of idiopathic gastroparesis: The NORIG randomized clinical trial. JAMA - J Am Med Assoc. 2013.

  139. Malamood M, Roberts A, Kataria R, Parkman HP, Schey R. Mirtazapine for symptom control in refractory gastroparesis. Drug Des Devel Ther. 2017.

  140. Gooden JY, Takahashi PY. Mirtazapine treatment of diabetic gastroparesis as a novel method to reduce tube-feed residual: A case report. J Med Case Rep. 2013.

  141. Johnstone M, Buddhdev P, Peter M, Diggory R. Mirtazapine: A solution for postoperative gastroparesis? BMJ Case Rep. 2009.

  142. Kim SW, Shin IS, Kim JM, Kang HC, Mun JU, Yang SJ, et al. Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic treatment. Psychosomatics. 2006.

  143. Nakamura K, Tomita T, Oshima T, Asano H, Yamasaki T, Okugawa T, et al. A double-blind placebo controlled study of acotiamide hydrochloride for efficacy on gastrointestinal motility of patients with functional dyspepsia. J Gastroenterol. 2017.

  144. Kusunoki H, Haruma K, Manabe N, Imamura H, Kamada T, Shiotani A, et al. Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: Randomized controlled study evaluation by real-time ultrasonography. Neurogastroenterol Motil. 2012.

  145. Altan E, Masaoka T, Farré R, Tack J. Acotiamide, a novel gastroprokinetic for the treatment of patients with functional dyspepsia: Postprandial distress syndrome. Expert Rev Gastroenterol Hepatol. 2012.

  146. Matsueda K, Hongo M, Tack J, Saito Y, Kato H. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut. 2012.

  147. Tack J, Janssen P, Masaoka T, Farré R, Van Oudenhove L. Efficacy of Buspirone, a Fundus-Relaxing Drug, in Patients With Functional Dyspepsia. Clin Gastroenterol Hepatol. 2012.

  148. Pasricha TS, Pasricha PJ. Botulinum Toxin Injection for Treatment of Gastroparesis. Gastrointest Endosc Clin N Am. 2019.

  149. Ezzeddine D, Jit R, Katz N, Gopalswamy N, Bhutani MS. Pyloric injection of botulinum toxin for treatment of diabetic gastroparesis. Gastrointest Endosc. 2002.

  150. Miller LS, Szych GA, Kantor SB, Bromer MQ, Knight LC, Maurer AH, et al. Treatment of idiopathic gastroparesis with injection of botulinum toxin into the pyloric sphincter muscle. Am J Gastroenterol. 2002.

  151. 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.

  152. Coleski R, Anderson MA, Hasler WL. Factors associated with symptom response to pyloric injection of botulinum toxin in a large series of gastroparesis patients. Dig Dis Sci. 2009.

  153. Friedenberg FK, Palit A, Parkman HP, Hanlon A, Nelson DB. Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol. 2008.

  154. Arts J, Holvoet L, Caenepeel P, Bisschops R, Sifrim D, Verbeke K, et al. Clinical trial: A randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis. Aliment Pharmacol Ther. 2007.

  155. Pitt HA, Mann LL, Berquist WE, Ament ME, Fonkalsrud EW, Denbesten L. Chronic Intestinal Pseudo-obstruction: Management With Total Parenteral Nutrition and a Venting Enterostomy. Arch Surg. 1985.

  156. Murr MM, Sarr MG, Camilleri M. The Surgeon’s Role in the Treatment of Chronic Intestinal Pseudoobstruction. Am J Gastroenterol. 1995.

  157. Kim CH, Nelson DK. Venting percutaneous gastrostomy in the treatment of refractory idiopathic gastroparesis. Gastrointest Endosc. 1998.

  158. Tao J, Patel V, Mekaroonkamol P, Luo H, Li B, Guan Q, et al. Technical Aspects of Peroral Endoscopic Pyloromyotomy. Gastrointest Endosc Clini N Am. 2019.

  159. Khashab MA, Stein E, Clarke JO, Saxena P, Kumbhari V, Chander Roland B, et al. Gastric peroral endoscopic myotomy for refractory gastroparesis: first human endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2013.

  160. Rodriguez J, Strong AT, Haskins IN, Landreneau JP, Allemang MT, El-Hayek K, et al. Per-oral Pyloromyotomy (POP) for Medically Refractory Gastroparesis: Short Term Results From the First 100 Patients at a High Volume Center. Ann Surg. 2018.

  161. Gonzalez JM, Benezech A, Vitton V, Barthet M. G-POEM with antro-pyloromyotomy for the treatment of refractory gastroparesis: mid-term follow-up and factors predicting outcome. Aliment Pharmacol Ther. 2017.

  162. Mekaroonkamol P, Dacha S, Wang L, Li X, Jiang Y, Li L, et al. Gastric Peroral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of Life, and Reduces Health Care Use For Patients With Gastroparesis. Clin Gastroenterol Hepatol. 2019.

  163. Dacha S, Mekaroonkamol P, Li L, Shahnavaz N, Sakaria S, Keilin S, et al. Outcomes and quality-of-life assessment after gastric per-oral endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017.

  164. Malik Z, Kataria R, Modayil R, Ehrlich AC, Schey R, Parkman HP, et al. Gastric Per Oral Endoscopic Myotomy (G-POEM) for the Treatment of Refractory Gastroparesis: Early Experience. Dig Dis Sci. 2018.

  165. Rodriguez JH, Haskins IN, Strong AT, Plescia RL, Allemang MT, Butler RS, et al. Per oral endoscopic pyloromyotomy for refractory gastroparesis: initial results from a single institution. Surg Endosc. 2017.

  166. Aghaie Meybodi M, Qumseya B, Shakoor D, Lobner K, Vosoughi K, Ichkhanian Y, et al. Efficacy and feasibility of G-POEM in management of patients with refractory gastroparesis: a systematic review and meta-analysis. Endosc Int Open. 2019.

  167. Avalos DJ, Satiya J, Bashashati M, Zuckerman M, Mendoza-Ladd A, Sarosiek I, et al. Sa1584 - G-Poem Improves Clinical Symptoms and Gastric Emptying in Gastroparesis: A Systematic Review and Meta-Analysis. Gastroenterology. 2018.

  168. Snape WJ, Lin MS, Agarwal N, Shaw RE. Evaluation of the pylorus with concurrent intraluminal pressure and EndoFLIP in patients with nausea and vomiting. Neurogastroenterol Motil. 2016.

  169. Landreneau JP, Strong AT, El-Hayek K, Tu C, Villamere J, Ponsky JL, et al. Laparoscopic pyloroplasty versus endoscopic per-oral pyloromyotomy for the treatment of gastroparesis. Surg Endosc Other Intervent Tech. 2018.

  170. Brewer Gutierrez OI, Khashab MA. Stent Placement for the Treatment of Gastroparesis. Gastrointest Endos Clin North Am. 2019.

  171. Khashab MA, Besharati S, Ngamruengphong S, Kumbhari V, El Zein M, Stein EM, et al. Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video). Gastrointest Endosc. 2015.

  172. Atassi H, Abell TL. Gastric Electrical Stimulator for Treatment of Gastroparesis. Gastrointest Endos Clin North Am. 2019.

  173. Chu H, Lin Z, Zhong L, Mccallum RW, Hou X. Treatment of high-frequency gastric electrical stimulation for gastroparesis. J Gastroenterol Hepatol (Australia). 2012.

  174. Levinthal DJ, Bielefeldt K. Systematic review and meta-analysis: Gastric electrical stimulation for gastroparesis. Autonomic Neuroscience: Basic and Clinical. 2017.

  175. Abell TL, McCallum RW, May KP, Wilson L, Parkman HP, Hasler WL, et al. 296 Effectiveness of Gastric Electrical Stimulation in Gastroparesis: Results From a Large Prospectively Collected Database of a National Gastroparesis Registry. Gastroenterology. 2015.

  176. Ducrotté P, Coffin B, Mathieu N, fontaine sébastien, Varannes SB des, Zerbib F, et al. Gastric Electrical Stimulation (Ges) for Refractory Vomiting: Results of a Prospective Multicenter Double-Blinded Randomized Controlled Cross-Over Trial. Gastroenterology. 2017.

  177. Shada AL, Dunst CM, Pescarus R, Speer EA, Cassera M, Reavis KM, et al. Laparoscopic pyloroplasty is a safe and effective first-line surgical therapy for refractory gastroparesis. Surg Endosc. 2016.

  178. Toro JP, Lytle NW, Patel AD, Davis SS, Christie JA, Waring JP, et al. Efficacy of laparoscopic pyloroplasty for the treatment of gastroparesis. J Am Coll Surg. 2014.

  179. Mancini SA, Angelo JL, Peckler Z, Philp FH, Farah KF. Pyloroplasty for refractory gastroparesis. Am Surg. 2015.

  180. Hibbard ML, Dunst CM, Swanström LL. Laparoscopic and Endoscopic Pyloroplasty for Gastroparesis Results in Sustained Symptom Improvement. J Gastrointest Surg. 2011.

  181. Sarosiek I. Gastric Electrical Stimulation (GES) and Pyloroplasty for the Treatment of Gastroparesis (GES + PP). ClinicalTrials.gov. 2017.

  182. Zihni AM, Dunst CM, Swanström LL. Surgical Management for Gastroparesis. Gastrointest Endosc Clin North Am. 2019.

  183. Sarosiek I, Davis B, Eichler E, McCallum RW. Surgical Approaches to Treatment of Gastroparesis. Gastroenterol Clin North Am. 2014.

  184. Bhayani NH, Sharata AM, Dunst CM, Kurian AA, Reavis KM, Swanstrom LL. End of the Road for a Dysfunctional End Organ: Laparoscopic Gastrectomy for Refractory Gastroparesis. J Gastrointest Surg. 2015.

  185. Sun Z, Rodriguez J, McMichael J, Chand B, Nash D, Brethauer S, et al. Surgical treatment of medically refractory gastroparesis in the morbidly obese. Surg Endosc. 2015.

  186. Meyer A, Pallati P, Shaligram A, Oleynikov D, Goede M. Partial longitudinal gastrectomy: a novel curative approach for gastroparesis. Proc 2012 Annu Meet Soc Am Gastrointest Endosc Surg. 2012;249.

  187. Watkins PJ, Buxton-Thomas MS, Howard ER. Long-term outcome after gastrectomy for intractable diabetic gastroparesis. Diabet Med. 2003.

  188. Zehetner J, Ravari F, Ayazi S, Skibba A, Darehzereshki A, Pelipad D, et al. Minimally invasive surgical approach for the treatment of gastroparesis. Surg Endosc. 2013.

  189. Kwon Y, Kim HJ, Lo Menzo E, Park S, Szomstein S, Rosenthal RJ. Anemia, iron and vitamin B12 deficiencies after sleeve gastrectomy compared to Roux-en-Y gastric bypass: A meta-analysis. Surg Obes Relat Dis. 2014.

  190. Ramadan M, Loureiro M, Laughlan K, Caiazzo R, Iannelli A, Brunaud L, et al. Risk of Dumping Syndrome after Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: Early Results of a Multicentre Prospective Study. Gastroenterol Res Pract. 2016.

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Sullivan, A., Temperley, L. & Ruban, A. Pathophysiology, Aetiology and Treatment of Gastroparesis. Dig Dis Sci 65, 1615–1631 (2020). https://doi.org/10.1007/s10620-020-06287-2

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