Abstract
Prolonged recordings of esophageal motility haveshown that dynamic changes of lower esophageal sphincter(LES) pressure such as transient LES relaxation and LESpressure drifts are the most common mechanisms underlying gastroesophageal reflux (GER). Thecoexistence of a delayed gastric emptying has also beenreported in a high proportion of patients with refluxdisease. However, not much information is available on the effects of antireflux therapy on thepathogenetic mechanisms of GER. The purpose of thisstudy was to determine in a group of children withsevere reflux disease the effect of omeprazole therapy on motor changes of LES underlying GER as wellas on gastric emptying time. Twenty-two children (medianage: 6.6 years) with GER disease, refractory to combinedranitidine and cisapride administration, entered into an eight-week omeprazole course.Ten subjects with moderate GER disease served ascontrols (median age: 6.0 years). Before and afteromeprazole administration, the following variables were assessed: esophagitis grading, fasting and fedsimultaneous prolonged recording of distal esophagealsphincter pressure (with a sleeve catheter) andintraesophageal pH, LES and esophageal peristalsisamplitude, and gastric emptying time of a mixedsolid-liquid meal (measured with gastric ultrasound). Ascompared to controls, patients showed a higher rate oftransient LES relaxation and LES pressure drift (P <0.01), a reduced amplitude of basal sphincter pressure(P < 0.01) and peristalsis (P < 0.05), and a moreprolonged gastric emptying time (P < 0.05). Afterending omeprazole, there was no significant change inany of the motor abnormalities of the esophagus and ingastric emptying time despite a marked improvement ofsymptoms and esophagitis in all patients. Sixteenpatients were symptomatic when reevaluated on a clinical basis two months after ending therapy. Weconclude that in children with severe GER disease, anabnormally high rate of both transient LES relaxationand LES pressure drift and slow gastric emptying are not affected by omperazole treatment, eventhough esophageal mucosal damage is markedly improved orcured. These abnormalities represent a primary motordisorder and can be implicated in the refractoriness of reflux disease.
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REFERENCES
Holloway RH, Orenstein SR: Gastro-esophageal reflux disease in adults and children. Bailliere's Clin Gastroenterol 5:337–370, 1991
Cohen S, Harris LD: The lower esophageal sphincter. Gastroenterology 63:1066–1073, 1972
Cucchiara S, Staiano A, DiLorenzo C, D'Ambrosio R, Andreotti MR, Prato M, et al: Esophageal motor abnormalities in children with gastroesophageal reflux and peptic esophagitis. J Pediatr 108:907–910, 1986
Kahrilas PJ, Dodds WJ, Hogan WJ, Kern M, Arndorfer RC, Reece A: Esophageal peristaltic dysfunction in peptic esophagitis. Gastroenterology 91:897–904, 1986
Hillemeier AC, Lange R, McCallum R, Seashore J, Gryboski J: Delayed gastric emptying in infants with gastroesophageal reflux. J Pediatr 98:190–193, 1981
Cucchiara S, Bortolotti M, Colombo C, Boccieri A, De Stefano M, Vitiello G, Pagano A, Ronchi A, Auricchio S: Abnormalities of gastrointestinal motility in children with gastroesophageal reflux disease. Dig Dis Sci 36:1066–1073, 1991
Mittal RK, Holloway RH, Penagini R, Ashley Blackshaw L, Dent J: Transient lower esophageal sphincter relaxation. Gastroenterology 109:601–610, 1995
Dent J, Holloway RH, Toouli J, Dodds WJ: Mechanisms of lower esophageal sphincter incompetence in patients with symptomatic gastroesophageal reflux. Gut 29:1020–1028, 1988
Cucchiara S, Bortolotti M, Minella R, Auricchio S: Fasting and postprandial mechanisms of gastroesophageal reflux in children with gastroesophageal reflux disease. Dig Dis Sci 38:86–92, 1993
Mittal RK, McCallum RW: Characteristics and frequency of transient relaxations of the lower esophageal sphincter in patients with reflux esophagitis. Gastroenterology 95:593–599, 1988
Colin Jones DG: Histamine H2 receptor antagonists in gastroesophageal reflux. Gut 30:1305–1308, 1989
Tytgat GNJ, Nio CY, Schotborgh RH: Reflux esophagitis. Scand J Gastroenterol 25(suppl 175):1–12, 1990
Cucchiara S, Minella R, Iervolino C, Franco MT, Campanozzi A, Franceschi M, D'Armiento F, Auricchio S: Omeprazole and high dose ranitidine in the treatment of refractory reflux esophagitis. Arch Dis Child 69:655–659, 1993
Gunasekaran TS, Hassall EG: Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. J Pediatr 123:148–154, 1993
Chakraborty TK, DeCaestecker JS, Pryde A, Heading RC: Effect of omeprazole on lower esophageal function in normal subjects. Aliment Pharmacol Ther 1:627–631, 1987
Howard JM, Reynolds RPE, Frei JV, Flowers MA, McDonalds TJ, Tilbe K, Bondy DC: Macroscopic healing of esophagitis does not improve esophageal motility. Dig Dis Sci 39:648–654, 1994
Cucchiara S, Minella R, Iorio R, Emiliano M, Az-Zeqeh N, Vallone G, Bali MA, Alfieri E, Scoppa A: Real-time ultrasound reveals gastric motor abnormalities in children investigated for dyspeptic symptoms. J Pediatr Gastroenterol Nutr 21:446–453, 1995
Ahtaridis G, Snape WJ, Cohen S: Clinical and manometric findings in benign peptic strictures of the esophagus. Dis Dis Sci 24:858–861, 1979
Eriksen CA, Sadek SA, Cranford C, Sutton D, Kennedy N, Cuschieri A: Reflux esophagitis and esophageal transit: evidence for a primary motor disorder. Gut 29:448–452, 1988
Marshal JB, Gerhardt DC: Improvement in esophageal motor dysfunction with treatment of reflux esophagitis: A report of two cases. Am J Gastroenterol 77:351–354, 1982
Sonnenberg A, Lepsien G, Muller-Lissner SA, Koelz HR, Siewert R, Blum AL: When is esophagitis healed? Esophageal endoscopy, histology, and function before and after cimetidine treatment. Dig Dis Sci 27:297–302, 1982
Katz PO, Knuff TF, Benjamin SB, Castell DO: Abnormal esophageal pressures in reflux esophagitis: cause or effect? Am J Gastroenterol 81:744–746, 1986
Allen ML, McIntosh DL, Robinson MG: Healing or amelioration of esophagitis does not result in increased lower esophageal sphincter or esophageal contractile pressure. Am J Gastroenterol 85:1331–1334, 1990
Eckardt VF: Does healing of esophagitis improve esophageal motor function. Dig Dis Sci 33:161–165, 1988
Singh P, Adamopoulos A, Taylor RH, Colin-Jones DG: Esophageal motor function before and after healing of esophagitis. Gut 33:1590–1596, 1992
Williams D, Thompson DG, Heggie L, O'Hanrahan T, Bancewicz J: Esophageal clearance function following treatment of esophagitis. Gastroenterology 106:108–116, 1994
Baldi F, Longanesi A, Ferrarini F, Michieletti G, Morselli-Labate AM: Esophageal motor function and outcome of treatment with H2 blockers in erosive esophagitis. J Gastrointest Motil 4:165–171, 1992
Durazo FA, Valenzuela JE: Effect of single and repeated doses of metoclopramide on the mechanisms of gastroesophageal reflux. Am J Gastroenterol 88:1657–1662, 1993
Downton J, Dent J, Heddle R, Toouli J, Buckle PJ, MacKinnon AM, Wyman JB: Elevation of gastric pH heals peptic esophagitis—a role for omeprazole. J Gastroenterol Hepatol 2:317–324, 1987
Holloway RH, Hongo M, Berger K, McCallum RW: Gastric distension: A mechanism for post-prandial gastroesophageal reflux. Gastroenterology 89:770–784, 1985
Franzi SJ, Martin CJ, Cox MR, Dent J: Response of canine lower esophageal sphincter to gastric distension. Am J Physiol 259:G380–G385, 1990
Dent J: Gastroesophageal reflux disease: A primary motility disorder. In Gastroin testinal Dysmotility: Focus on Cisapride. RC Heading, JD Wood (eds). New York, Raven Press, 1992, pp 127–139
Wyman JB, Dent J, Heddle R, Dodds WJ, Toouli J, Downton J: Control of belching by the lower esophageal sphincter. Gut 31:639–646, 1990
Patrikos J, Martin CJ, Dent J: Relationship of transient lower esophageal sphincter relaxation to post-prandial gastroesophageal reflux and belching in dogs. Gastroenterology 90:545–551, 1986
Cucchiara S, Devizia B, Minella R, Calabrese F, Scoppa A, Alfieri E, Borrelli O, Salvia G, Az-Zeqeh N: Effects of intragastric volume and osmolality on mechanisms of gastroesophageal reflux in children with reflux disease. Gastroenterology 108:A587, 1995
Orenstein S: Gastresophgeal reflux. In Pediatric Gastrointestinal Motility Disorders. PE Hyman (ed). New York, Academy Professional Information Services, 1977, pp 55–88
Cucchiara S, Campanozzi A, Greco L, Franco MT, Emiliano M, Alfieri E, Calabrese F, Numeroso V: Predictive value of esophageal manometry and gastroesophageal pH monitoring on responsiveness of reflux disease to medical therapy in children. Am J Gastroenterol 90:1791–1796, 1996
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Cucchiara, S., Minella, R., Campanozzi, A. et al. Effects of Omeprazole on Mechanisms of Gastroesophageal Reflux in Childhood. Dig Dis Sci 42, 293–299 (1997). https://doi.org/10.1023/A:1018853516206
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DOI: https://doi.org/10.1023/A:1018853516206