Dyspepsia: Organic versus functional

Journal of Clinical Gastroenterology

Volumn 46, Issue 3, 2012, Pages 175-190

  Oustamanolakis, Pantelis ^a,b   Tack, Jan ^a,b  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

dyspepsia; functional dyspepsia; functional gastrointestinal disorders; organic dyspepsia

Indexed keywords

AMOXICILLIN; ANTACID AGENT; ANTIBIOTIC AGENT; AZITHROMYCIN; CHOLECYSTOKININ; CISAPRIDE; CLARITHROMYCIN; CYCLOOXYGENASE 2 INHIBITOR; DIGITALIS; DOMPERIDONE; ERYTHROMYCIN; ESTROGEN; GHRELIN; GSK 962040; HISTAMINE H2 RECEPTOR ANTAGONIST; ITOPRIDE; LEVODOPA; METOCLOPRAMIDE; MISOPROSTOL; MITEMCINAL; MOSAPRIDE; NARCOTIC AGENT; NONSTEROID ANTIINFLAMMATORY AGENT; ORAL CONTRACEPTIVE AGENT; PLACEBO; PROKINETIC AGENT; PROTON PUMP INHIBITOR; SUCRALFATE; THEOPHYLLINE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ABDOMINAL PAIN; ACCOMMODATION; BAROSTAT; BELCHING; BILE DUCT DISEASE; BLOATING; BREATH ANALYSIS; CHRONIC GASTRITIS; DYSPEPSIA; ECHOGRAPHY; EPIGASTRIC DISCOMFORT; EPIGASTRIC FULLNESS; ESOPHAGUS CANCER; FUNCTIONAL DYSPEPSIA; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL ENDOSCOPY; GENETIC HETEROGENEITY; GENETIC PREDISPOSITION; HEARTBURN; HELICOBACTER INFECTION; HELICOBACTER PYLORI; HUMAN; INDIGESTION; MANOMETRY; MYOELECTRIC CONTROL; NAUSEA; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUTRITIONAL INTOLERANCE; PANCREAS DISEASE; PATHOGENESIS; PATHOPHYSIOLOGY; PEPTIC ULCER; PREVALENCE; PRIORITY JOURNAL; REVIEW; SATIETY; SENSORIMOTOR FUNCTION; SOCIAL PSYCHOLOGY; STOMACH CANCER; STOMACH DISTENSION; STOMACH EMPTYING; STOMACH MOTILITY; STOMACH PARESIS; STOMACH SCINTISCANNING; VOMITING;

ADULT; DYSPEPSIA; GASTROINTESTINAL DISEASES; HELICOBACTER INFECTIONS; HELICOBACTER PYLORI; HUMANS; MIDDLE AGED; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84856850437     PISSN: 01920790     EISSN: 15392031     Source Type: Journal    
DOI: 10.1097/MCG.0b013e318241b335     Document Type: Review

References (210)

1. Drossman DA, Thompson GW, Talley NJ, et al. Identification of subgroups of functional gastrointestinal disorders. Gastroenterol Int. 1990;3:159-172.
2. Talley NJ, Stanghellini V, Heading RC, et al. Functional gastroduodenal disorders. Gut. 1999;45(suppl 2:II):37-42.
3. Tack J, Bisschops R, Sarnelli G. Pathophysiology and treatment of functional dyspepsia. Gastroenterology. 2004; 127:1239-1255. (Pubitemid 39345892)
4. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006;130:1466-1479.
5. Feinle-Bisset C, Vozzo R, Horowitz M, et al. Diet, food intake, and disturbed physiology in the pathogenesis of symptoms in functional dyspepsia. Am J Gastroenterol. 2004;99:170-181. (Pubitemid 38679120)
6. Agreus L. Natural history of dyspepsia. Gut. 2002;50(suppl 4 iv):2-9.
7. Piessevaux H, De Winter B, Louis E, et al. Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings. Neurogastroenterol Motil. 2009;21:378-388.
8. Agreus L, Svardsudd K, Nyren O, et al. Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time. Gastroenterology. 1995; 109:671-680.
9. El-Serag HB, Talley NJ. Systematic review: the prevalence and clinical course of functional dyspepsia. Aliment Pharmacol Ther. 2004;19:643-654. (Pubitemid 38445425)
10. Tougas G, Chen Y, Hwang P, et al. Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: findings from the DIGEST study. Domestic/International Gastroenterology Surveillance Study. Am J Gastroenterol. 1999;94:2845-2854. (Pubitemid 29482745)
11. Camilleri M, Dubois D, Coulie B, et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study. Clin Gastroenterol Hepatol. 2005;3:543-552. (Pubitemid 40824747)
12. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci. 1993;38:1569-1580. (Pubitemid 23271409)
13. Jones RH, Lydeard SE, Hobbs FD, et al. Dyspepsia in England and Scotland. Gut. 1990;31:401-405. (Pubitemid 20129436)
14. Klauser AG, Voderholzer WA, Knesewitsch PA, et al. What is behind dyspepsia? Dig Dis Sci. 1993;38:147-154.
15. Enck P, Dubois D, Marquis P. Quality of life in patients with upper gastrointestinal symptoms: results from the Domestic/ International Gastroenterology Surveillance Study (DIGEST). Scand J Gastroenterol. 1999;231:48-54. (Pubitemid 29510677)
16. Talley NJ, Zinsmeister AR, Schleck CD, et al. Dyspepsia and dyspepsia subgroups: a population-based study. Gastroenterology. 1992;102:1259-1268.
17. Agreus L, Borgquist L. The cost of gastro-oesophageal reflux disease, dyspepsia and peptic ulcer disease in Sweden. Pharmacoeconomics. 2002;20:347-355. (Pubitemid 34569368)
18. Penston JG, Pounder RE. A survey of dyspepsia in Great Britain. Aliment Pharmacol Ther. 1996;10:83-89. (Pubitemid 26070003)
19. Koloski NA, Talley NJ, Boyce PM. Predictors of health care seeking for irritable bowel syndrome and nonulcer dyspepsia: a critical review of the literature on symptom and psychosocial factors. Am J Gastroenterol. 2001;96:1340-1349. (Pubitemid 32455057)
20. Moayyedi P, Talley NJ, Fennerty MB, et al. Can the clinical history distinguish between organic and functional dyspepsia? JAMA. 2006;295:1566-1576.
21. Bardella MT, Minoli G, Ravizza D, et al. Increased prevalence of celiac disease in patients with dyspepsia. Arch Intern Med. 2000;160:1489-1491. (Pubitemid 30327453)
22. Locke GR III, Murray JA, Zinsmeister AR, et al. Celiac disease serology in irritable bowel syndrome and dyspepsia: a population-based case-control study. Mayo Clin Proc. 2004;79:476-482. (Pubitemid 38401767)
23. Vakil N, Moayyedi P, Fennerty MB, et al. Limited value of alarm features in the diagnosis of upper gastrointestinal malignancy: systematic review and meta-analysis. Gastroenterology. 2006;131:390-401. (Pubitemid 44142444)
24. Hammer J, Eslick GD, Howell SC, et al. Diagnostic yield of alarm features in irritable bowel syndrome and functional dyspepsia. Gut. 2004;53:666-672. (Pubitemid 38561444)
25. Ofman JJ, MacLean CH, Straus WL, et al. Meta-analysis of dyspepsia and nonsteroidal anti-inflammatory drugs. Arthritis Rheum. 2003;49:508-518. (Pubitemid 36992191)
26. Ford AC, Marwaha A, Lim A, et al. What is the prevalence of clinically significant endoscopic findings in subjects withdyspepsia? Systemtic review and meta-analysis. Clin Gastroenterol Hepatol. 2010;8:830-837.
27. Wallace MB, Durkalski VL, Vaughan J, et al. Age and alarm symptoms do not predict endoscopic findings among patients with dyspepsia: a multicentre database study. Gut. 2001; 49:29-34. (Pubitemid 32601876)
28. Bowrey DJ, Griffin SM, Wayman J, et al. Use of alarm symptoms to select dyspeptics for endoscopy causes patients with curable esophagogastric cancer to be overlooked. Surg Endosc. 2006;20:1725-1728. (Pubitemid 44715537)
29. Bai Y, Li ZS, Zou DW, et al. Alarm features and age for predicting upper gastrointestinal malignancy in Chinese patients with dyspepsia with high background prevalence of Helicobacter pylori infection and upper gastrointestinal malignancy: an endoscopic database review of 102,665 patients from 1996 to 2006. Gut. 2010;59:722-728.
30. Boekema P, van Dam van Isselt EF, Bots ML, et al. Functional bowel symptoms in a general Dutch population and associations with common stimulants. Neth J Med. 2001;59:23-30. (Pubitemid 32618644)
31. Hammer J, Führer M, Pipal L, et al. Hypersensitivity for capsaicin in patients with functional dyspepsia. Neurogastroenterol Motil. 2008;20:125-133.
32. Spiegel BM, Farid M, Dulai GS, et al. Comparing rates of dyspepsia with coxibs vs NSAID+PPI: a meta-analysis. Am J Med. 2006;119:e27-e36.
33. Quartero AO, de Wit NJ, Lodder AC, et al. Disturbed solidphase gastric emptying in functional dyspepsia: a metaanalysis. Dig Dis Sci. 1998;43:2028-2033.
34. Sarnelli G, Caenepeel P, Geypens B, et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 2003; 98:783-788. (Pubitemid 36576302)
35. Stanghellini V, Tosetti C, Paternico A, et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology. 1996;110:1036-1042. (Pubitemid 26113742)
36. Perri F, Clemente R, Festa V, et al. Patterns of symptoms in functional dyspepsia: role of Helicobacter pylori infection and delayed gastric emptying. Am J Gastroenterol. 1998;93: 2082-2088. (Pubitemid 29076855)
37. 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; 96:1422-1428. (Pubitemid 32455069)
38. Talley NJ, Locke GR III, Lahr BD, et al. Functional dyspepsia, delayed gastric emptying and impaired quality of life. Gut. 2006;23:923-936.
39. Janssen P, Vanden Berghe P, Verschueren S, et al. Review article: the role of gastric motility in the control of food intake. Aliment Pharmacol Ther. 2011;33:880-894.
40. Carbonnel F, Lemann M, Rambaud JC, et al. Effect of the energy density of a solid-liquid meal on gastric emptying and satiety. Am J Clin Nutr. 1994;60:307-311. (Pubitemid 24278729)
41. Kusano M, Zai H, Shimoyama Y, et al. Rapid gastric emptying, rather than delayed gastric emptying, might provoke functional dyspepsia. J Gastroenterol Hepatol. 2011;26(suppl 3):75-78.
42. Kindt S, Tack J. Impaired gastric accommodation and its role in dyspepsia. Gut. 2006;55:1685-1691. (Pubitemid 44893562)
43. Azpiroz F, Malagelada JR. Importance of vagal input in maintaining gastric tone in the dog. J Physiol. 1987;384: 511-524. (Pubitemid 17026533)
44. Coulie B, Tack J, Sifrim D, et al. Role of nitric oxide in fasting gastric fundus tone and in 5-HT1 receptormediated relaxation of gastric fundus. Am J Physiol. 1999;276: G373-G377. (Pubitemid 29104150)
45. Desai KM, Sessa WC, Vane JR. Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid. Nature. 1991;351:477-479. (Pubitemid 21896622)
46. Jahnberg T, Abrahamsson H, Jansson G, et al. Gastric relaxatory response to feeding before and after vagotomy. Scand J Gastroenterol. 1977;12:225-228. (Pubitemid 8163059)
47. Vanden Berghe P, Janssen P, Kindt S, et al. Contribution of different triggers to the gastric accommodation reflex in humans. Am J Physiol Gastrointest Liver Physiol. 2009; 297:G902-G906.
48. Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology. 1998;115:1346-1352. (Pubitemid 28545984)
49. Tack J, Demedts I, Dehondt G, et al. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology. 2002;122:1738-1747. (Pubitemid 34651416)
50. Kim DY, Delgado-Aros S, Camilleri M, et al. Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia. Am J Gastroenterol. 2001; 96:3099-3105. (Pubitemid 33095347)
51. Boeckxstaens GE, Hirsch DP, Kuiken SD, et al. The proximal stomach and postprandial symptoms in functional dyspeptics. Am J Gastroenterol. 2002;97:40-48. (Pubitemid 34059762)
52. Moragas G, Azpiroz F, Pavia J, et al. Relations among intragastric pressure, postcibal perception, and gastric emptying. Am J Physiol. 1993;264:G1112-G1117. (Pubitemid 23196816)
53. Janssen P, Pottel H, Vos R, et al. Endogenously released opioids mediate meal-induced gastric relaxation via peripheral mu-opioid receptors. Aliment Pharmacol Ther. 2011;33: 607-614.
54. Geeraerts B, Vanden Berghe J, Van Oudenhove L, et al. Influence of experimentally induced anxiety on gastric sensorimotor function in humans. Gastroenterology. 2005;129: 1437-1444. (Pubitemid 41597386)
55. Ameloot K, Janssen P, Scarpellini E, et al. Endocannabinoid control of gastric sensorimotor function in man. Aliment Pharmacol Ther. 2010;31:1123-1131.
56. Camilleri M, Coulie B, Tack J. Visceral hypersensitivity: facts, speculations and challenges. Gut. 2001;48:125-131. (Pubitemid 32042653)
57. Simrén M, Tack J. Functional dyspepsia: evaluation and treatment. Gastroenterol Clin North Am. 2003;32:577-599. (Pubitemid 36807584)
58. Mertz H, Fullerton S, Naliboff B, et al. Symptoms and visceral perception in severe functional and organic dyspepsia. Gut. 1998;42:814-822. (Pubitemid 28277222)
59. Holtmann G, Gschossmann J, Neufang-Huber J, et al. Differences in gastric mechanosensory function after repeated ramp distensions in non-consulters with dyspepsia and healthy controls. Gut. 2000;47:332-336.
60. Tack J, Caenepeel P, Corsetti M, et al. Role of tension receptors in dyspeptic patients with hypersensitivity to gastric distention. Gastroenterology. 2004;127:1058-1066. (Pubitemid 39345875)
61. Vandenberghe J, Dupont P, Van Oudenhove L, et al. Regional cerebral blood flow during gastric balloon distention in functional dyspepsia. Gastroenterology. 2007;132: 1684-1693. (Pubitemid 46677948)
62. Vandenberghe J, Vos R, Persoons P, et al. Dyspeptic patients with visceral hypersensitivity: sensitisation of pain specific or multimodal pathways? Gut. 2005;54:914-919. (Pubitemid 40873900)
63. Tack J. Gastric motor and sensory function. Curr Opin Gastroenterol. 2009;25:557-565.
64. van den Elzen BD, Tytgat GN, et al. Gastric hypersensitivity induced by oesophageal acid infusion in healthy volunteers. Neurogastroenterol Motil. 2009;21:160-169.
65. Geeraerts B, Mimidis K, van Oudenhove L, et al. Role of endogenous opioids in the control of gastric sensorimotor function. Neurogastroenterol Motil. 2008;20:1094-1102.
66. Van Oudenhove L, Vandenberghe J, Dupont P, et al. Abnormal regional brain activity during rest and (anticipated) gastric distension in functional dyspepsia and the role of anxiety: a H(2)(15)O-PET study. Am J Gastroenterol. 2010; 105:913-924.
67. Van Oudenhove L, Vandenberghe J, Dupont P, et al. Regional brain activity in functional dyspepsia: a H(2)(15)O-PET study on the role of gastric sensitivity and abuse history. Gastroenterology. 2010;139:36-47.
68. Geeraerts B, Van Oudenhove L, Fischler B, et al. Influence of abuse history on gastric sensorimotor function in functional dyspepsia. Neurogastroenterol Motil. 2009;21:33-41.
69. Van Oudenhove L, Vandenberghe J, Geeraerts B, et al. Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation? Gut. 2008;57:1666-1673.
70. Feinle C, D'Amato M, Read NW. Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid. Gastroenterology. 1996; 110:1379-1385. (Pubitemid 26134068)
71. Feinle C, Rades T, Otto B, et al. Fat digestion modulates gastrointestinal sensations induced by gastric distention and duodenal lipid in humans. Gastroenterology. 2001;120: 1100-1107. (Pubitemid 32246664)
72. Feinle C, Meier O, Otto B, et al. Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia. Gut. 2001;48:347-355. (Pubitemid 32269562)
73. Feinle C, Read NW. Ondansetron reduces nausea induced by gastroduodenal stimulation without changing gastric motility. Am J Physiol. 1996;271:G591-G597.
74. Accarino AM, Azpiroz F, Malagelada JR. Modification of small bowel mechanosensitivity by intestinal fat. Gut. 2001;48:690-695. (Pubitemid 32378592)
75. Zerbib F, Bruley Des Varannes S, Scarpignato C, et al. Endogenous cholecystokinin in postprandial lower esophageal sphincter function and fundic tone in humans. Am J Physiol. 1998;275:G1266-G1273.
76. DeMarchi B, Vos R, Deprez P, et al. Influence of a lipase inhibitor on gastric sensitivity and accommodation to an orally ingested meal. Aliment Pharmacol Ther. 2004;19: 1261-1268. (Pubitemid 38859502)
77. Samsom M, Verhagen MA, vanBerge Henegouwen GP, et al. Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients. Gastroenterology. 1999;116:515-520. (Pubitemid 29106757)
78. Lee KJ, Demarchi B, Demedts I, et al. A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nausea. Am J Gastroenterol. 2004;99:1765-1773. (Pubitemid 39237506)
79. Bratten J, Jones MP. Prolonged recording of duodenal acid exposure in patients with functional dyspepsia and controls using a radiotelemetry pH monitoring system. J Clin Gastroenterol. 2009;43:527-533.
80. di Stefano M, Vos R, Vanuytsel T, et al. Prolonged duodenal acid perfusion and dyspeptic symptom occurrence in healthy volunteers. Neurogastroenterol Motil. 2009;21: e712-e740.
81. Camilleri M, Brown ML, Malagelada JR. Relationship between impaired gastric emptying and abnormal gastrointestinal motility. Gastroenterology. 1986;91:1765-1773.
82. Wilmer A, Van Cutsem E, Andrioli A, et al. Ambulatory gastrojejunal manometry in severe motility-like dyspepsia: lack of correlation between dysmotility, symptoms, and gastric emptying. Gut. 1998;42:235-242. (Pubitemid 28212179)
83. Pfaffenbach B, Adamek RJ, Bartholomaus C, et al. Gastric dysrhythmias and delayed gastric emptying in patients with functional dyspepsia. Dig Dis Sci. 1997;42:2094-2099. (Pubitemid 27501996)
84. Parkman HP, Miller MA, Trate D, et al. Electrogastrography and gastric emptying scintigraphy are complementary for assessment of dyspepsia. J Clin Gastroenterol. 1997;24: 214-219. (Pubitemid 27310589)
85. Lin Z, Eaker EY, Sarosiek I, et al. Gastric myoelectrical activity and gastric emptying in patients with functional dyspepsia. Am J Gastroenterol. 1999;94:2384-2389. (Pubitemid 29420661)
86. Hausken T, Svebak S, Wilhelmsen I, et al. Low vagal tone and antral dysmotility in patients with functional dyspepsia. Psychosom Med. 1993;55:12-22. (Pubitemid 23070009)
87. Holtmann G, Goebell H, Jockenhoevel F, et al. Altered vagal and intestinal mechanosensory function in chronic unexplained dyspepsia. Gut. 1998;42:501-506. (Pubitemid 28186566)
88. Troncon LE, Thompson DG, Ahluwalia NK, et al. Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomy. Gut. 1995;37:17-22.
89. Khoo J, Rayner CK, Feinle-Bisset C, et al. Gastrointestinal hormonal dysfunction in gastroparesis and functional dyspepsia. Neurogastroenterol Motil. 2010;22:1270-1278.
90. Murphy KG, Dhillo WS, Bloom SR. Gut peptides in the regulation of food intake and energy homeostasis. Endocr Rev. 2006;27:719-727. (Pubitemid 44936055)
91. Chua AS, Keeling PW. Cholecystokinin hyperresponsiveness in functional dyspepsia. World J Gastroenterol. 2006;12: 2688-2693. (Pubitemid 43796477)
92. Pilichiewicz AN, Feltrin KL, Horowitz M, et al. Functional dyspepsia is associated with a greater symptomatic response to fat but not carbohydrate, increased fasting and postprandial CCK, and diminished PYY. Am J Gastroenterol. 2008;103:2613-2623.
93. Locke GR III, Zinsmeister AR, Talley NJ, et al. Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc. 2000;75:907-912.
94. Gathaiya N, Locke GR III, Camilleri M, et al. Novel associations with dyspepsia: a community-based study of familial aggregation, sleep dysfunction and somatization. Neurogastroenterol Motil. 2009;21:e922-e969.
95. Holtmann G, Siffert W, Haag S, et al. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004;126:971-979. (Pubitemid 38451168)
96. Tahara T, Arisawa T, Shibata T, et al. Homozygous 825T allele of the GNB3 protein influences the susceptibility of Japanese to dyspepsia. Dig Dis Sci. 2008;53:642-646. (Pubitemid 351317077)
97. Oshima T, Nakajima S, Yokoyama T, et al. The G-protein beta3 subunit 825TT genotype is associated with epigastric pain syndrome-like dyspepsia. BMC Med Genet. 2010;11:13(1-6).
98. Tahara T, Arisawa T, Shibata T, et al. COMT gene val158met polymorphism in patients with dyspeptic symptoms. Hepatogastroenterology. 2008;55:979-982. (Pubitemid 351975969)
99. Arisawa T, Tahara T, Shibata T, et al. Genetic polymorphisms of cyclooxygenase-1 (COX-1) are associated with functional dyspepsia in Japanese women. J Womens Health (Larchmt). 2008;17:1039-1043.
100. Tahara T, Arisawa T, Shibata T, et al. A genetic variant of the CD14 C-159T in patients with functional dyspepsia (FD) in Japanese subjects. J Clin Biochem Nutr. 2008;42:104-110. (Pubitemid 351912427)
101. Tahara T, Arisawa T, Shibata T, et al. Serotonin-2A receptor gene T102C polymorphism in patients with dyspeptic symptoms. Hepatogastroenterology. 2008;55:1921-1924.
102. Mearin F, Perez-Oliveras M, Perello A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: one-year follow-up cohort study. Gastroenterology. 2005;129:98-104. (Pubitemid 41002046)
103. Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2009; 29:765-773.
104. Walker MM, Salehian SS, Murray CE, et al. Implications of eosinophilia in the normal duodenal biopsy: an association with allergy and functional dyspepsia. Aliment Pharmacol Ther. 2010;31:1229-1236.
105. Kindt S, Tertychnyy A, de Hertogh G, et al. Intestinal immune activation in presumed postinfectious functional dyspepsia. Neurogastroenterol Motil. 2009;21:e832-e856.
106. Futagami S, Shindo T, Kawagoe T, et al. Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia. Am J Gastroenterol. 2010;105:1835-1842.
107. Kindt S, Van Oudenhove L, Broekaert D, et al. Immune dysfunction in patients with functional gastrointestinal disorders. Neurogastroenterol Motil. 2009;21:389-398.
108. Liebregts T, Adam B, Bredack C, et al. Small bowel homing T cells are associated with symptoms and delayed gastric emptying in functional dyspepsia. Am J Gastroenterol. 2011; 106:1089-1098.
109. Dizdar V, Spiller R, Singh G, et al. Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia-inducedpostinfectious irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2010;31:883-891.
110. Li X, Chen H, Lu H, et al. The study on the role of inflammatory cells and mediators in post-infectious functional dyspepsia. Scand J Gastroenterol. 2010;45:573-581.
111. Lai LH, Sung JJ. Helicobacter pylori and benign upper digestive disease. Best Pract Res Clin Gastroenterol. 2007;21:261-279. (Pubitemid 46421907)
112. Sarnelli G, Cuomo R, Janssens J, et al. Symptom patterns and pathophysiological mechanisms in dyspeptic patients with and without Helicobacter pylori. Dig Dis Sci. 2003;48: 2229-2236. (Pubitemid 38021724)
113. Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2011;2:CD002096.
114. Haug TT, Wilhelmsen I, Berstad A, et al. Life events and stress in patients with functional dyspepsia compared with patients with duodenal ulcer and healthy controls. Scand J Gastroenterol. 1995;30:524-530.
115. Drossman DA, Creed FH, Olden KW, et al. Psychosocial aspects of the functional gastrointestinal disorders. Gut. 1999;45(suppl 2):II25-II30. (Pubitemid 29434809)
116. Locke GR III, Weaver AL, Melton LJ III, et al. Psychosocial factors are linked to functional gastrointestinal disorders: a population based nested case-control study. Am J Gastroenterol. 2004;99:350-357. (Pubitemid 38279880)
117. Magni G, di Mario F, Bernasconi G, et al. DSM-III diagnoses associated with dyspepsia of unknown cause. Am J Psychiatry. 1987;144:1222-1223. (Pubitemid 17147534)
118. Haug TT, Svebak S, Wilhelmsen I, et al. Psychological factors and somatic symptoms in functional dyspepsia. A comparison with duodenal ulcer and healthy controls. J Psychosom Res. 1994;38:281-291. (Pubitemid 24135992)
119. Castillo EJ, Camilleri M, Locke GR, et al. A communitybased, controlled study of the epidemiology and pathophysiology of dyspepsia. Clin Gastroenterol Hepatol. 2004;21: 985-996. (Pubitemid 39539748)
120. Van Oudenhove L, Vandenberghe J, Vos R, et al. Risk factors for impaired health-related quality of life in functional dyspepsia. Aliment Pharmacol Ther. 2011;33:261-274.
121. Kindt S, Van Oudenhove L, Mispelon L, et al. Longitudinal and cross-sectional factors associated with long-term clinical course in functional dyspepsia: a 5-year follow-up study. Am J Gastroenterol. 2011;106:340-348.
122. Van Oudenhove L, Vandenberghe J, Vos R, et al. Factors associated with co-morbid irritable bowel syndrome and chronic fatigue-like symptoms in functional dyspepsia. Neurogastroenterol Motil. 2011;23:524-e202.
123. Jones MP, Talley NJ, Eslick GD, et al. Community subgroups in dyspepsia and their association with weight loss. Am J Gastroenterol. 2008;103:2051-2060.
124. Tack J, Caenepeel P, Fischler B, et al. Symptoms associated with hypersensitivity to gastric distension in functional dyspepsia. Gastroenterology. 2001;121:526-535. (Pubitemid 32822566)
125. Bisschops R, Karamanolis G, Arts J, et al. Relationship between symptoms and ingestion of a meal in functional dyspepsia. Gut. 2008;57:1495-1503.
126. Choung RS, Locke GR, Schleck CD, et al. Do distinct dyspepsia subgroups exist in the community? A populationbased study. Am J Gastroenterol. 2007;102:1983-1999.
127. van Kerkhoven LA, Laheij RJ, Meineche-Schmidt V, et al. Functional Dyspepsia: not all roads seem to lead to Rome. J Clin Gastroenterol. 2009;43:118-122.
128. Locke GR III, Zinsmeister AR, Fett SL, et al. Overlap of gastrointestinal symptom complexes in a US community. Neurogastroenterol Motil. 2005;17:29-34. (Pubitemid 40204009)
129. Johnsson F, Roth Y, Damgaard Pedersen NE, et al. Cimetidine improves GERD symptoms in patients selected by a validated GERD questionnaire. Aliment Pharmacol Ther. 1993;7:81-86. (Pubitemid 23053392)
130. Tack J, Caenepeel P, Arts J, et al. Prevalence of acid reflux in functional dyspepsia and its association with symptom profile. Gut. 2005;54:1370-1376. (Pubitemid 41375189)
131. Corsetti M, Caenepeel P, Fischler B, et al. Impact of coexisting irritable bowel syndrome on symptoms and pathophysiological mechanisms in functional dyspepsia. Am J Gastroenterol. 2004;99:1152-1159. (Pubitemid 38917823)
132. The Danish Dyspepsia Study Group. Value of the unaided clinical diagnosis in dyspeptic patients in primary care. Am J Gastroenterol. 2001;96:1417-1421.
133. Heikkinen M, Pikkarainen P, Eskelinen M, et al. GP's ability to diagnose dyspepsia based only on physical examination and patient history. Scand J Prim Health Care. 2000;18: 99-104. (Pubitemid 30468908)
134. Talley NJ, Vakil NB, Moayyedi P. American gastroenterological association technical review on the evaluation of dyspepsia. Gastroenterology. 2005;129:1756-1780. (Pubitemid 41597412)
135. Talley NJ, Vakil N. Practice Parameters Committee of the American College of Gastroenterology. Guidelines for the management of dyspepsia. Am J Gastroenterol. 2005;100: 2324-2337.
136. National Institute for Clinical Excellence. Dyspepsia: Managing Dyspepsia in Adults in Primary Care. London: NICE; 2004.
137. Mitchell RM, Collins JS, Watson RG, et al. Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists. Endoscopy. 2002;34:524-526. (Pubitemid 34711991)
138. Rabeneck L, Wristers K, Souchek J, et al. Impact of upper endoscopy on satisfaction in patients with previously uninvestigated dyspepsia. Gastrointest Endosc. 2003;57:295-299. (Pubitemid 36350782)
139. Lassen A, Pedersen F, Bytzer P, et al. Helicobacter pylori testand- eradicate versus prompt endoscopy for management of dyspeptic patients: a randomized trial. Lancet. 2000;356: 455-460. (Pubitemid 30496816)
140. Quadri A, Vakil N. Health-related anxiety and the effect of open-access endoscopy in US patients with dyspepsia. Aliment Pharmacol Ther. 2003;17:835-840. (Pubitemid 36418881)
141. HallisseyMT, Allum WH, Jewkes AJ, et al. Early detection of gastric cancer. BMJ. 1990;301:513-515. (Pubitemid 20320919)
142. Sue-Ling HM, Johnston D, Martin IG, et al. Gastric cancer: a curable disease in Britain. BMJ. 1993;307:591-596. (Pubitemid 23255064)
143. Canga C, Vakil N. Upper GI malignancy, uncomplicated dyspepsia, and the age threshold for early endoscopy. Am J Gastroenterol. 2002;97:600-603. (Pubitemid 34245886)
144. Ford AC, Qume M, Moayyedi P, et al. Helicobacter pylori "test and treat" or endoscopy for managing dyspepsia: an individual patient data meta-analysis. Gastroenterology. 2005;128:1838-1844. (Pubitemid 40824695)
145. Delaney B, Ford AC, Forman D, et al. Initial management strategies for dyspepsia. Cochrane Database Syst Rev. 2005; 4:CD001961.
146. Ofman J, Rabeneck L. The effectiveness of endoscopy in the management of dyspepsia: a qualitative systematic review. Am J Med. 1999;106:335-346. (Pubitemid 29153413)
147. Makris N, Barkun A, Crott R, et al. Cost-effectiveness of alternative approaches in the management of dyspepsia. Int J Technol Assess Health Care. 2003;19:446-464. (Pubitemid 38649114)
148. Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56: 772-781. (Pubitemid 46854190)
149. Ford AC, Delaney BC, Forman D, et al. Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients. Cochrane Database Syst Rev. 2006;2:CD003840.
150. Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006;2:CD002096.
151. Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut. 2001;49:347-353.
152. Delaney B, McColl K. Review article: Helicobacter pylori and gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2005;22(suppl 1):32-40. (Pubitemid 41153077)
153. Vakil N, Rhew D, Soll A, et al. The cost-effectiveness of diagnostic testing strategies for Helicobacter pylori. Am J Gastroenterol. 2000;95:1691-1698. (Pubitemid 30485003)
154. Chiba N, van Zanten SJ, Sinclair P, et al. Treating Helicobacter pylori infection in primary care patients with uninvestigated dyspepsia: the Canadian adult dyspepsia empiric treatment-Helicobacter pylori positive (CADETHp) randomised controlled trial. BMJ. 2002;324:1012-1016. (Pubitemid 34457514)
155. Delaney BC, Wilson S, Roalfe A, et al. Cost-effectiveness of initial endoscopy for dyspepsia in patients over age 50 years: a randomised controlled trial in primary care. Lancet. 2000;356:1965-1969.
156. Farkkila M, Sarna S, Valtonen V, et al. Does the "test- andtreat" strategy work in primary health care for management of uninvestigated dyspepsia? A prospective two-year follow-up study of 1552 patients. Scand J Gastroenterol. 2004;39:327-335. (Pubitemid 38526720)
157. Ford AC, Moayyedi P, Jarbol DE, et al. Meta-analysis: Helicobacter pylori "test and treat" compared with empirical acid suppression for managing dyspepsia. Aliment Pharmacol Ther. 2008;28:534-544.
158. McColl KE, Murray LS, Gillen D, et al. Randomised trial of endoscopy with testing for Helicobacter pylori compared with non-invasive H. pylori testing alone in the management of dyspepsia. BMJ. 2002;324:999-1002. (Pubitemid 34457507)
159. Jones R, Tait C, Sladen G, et al. A trial of a test-and-treat strategy for Helicobacter pylori positive dyspeptic patients in general practice. Int J Clin Pract. 1999;53:413-416. (Pubitemid 29433651)
160. Heaney A, Collins JSA, Watson RGP, et al. A prospective randomised trial of a "test and treat" policy versus endoscopy based management in young Helicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic. Gut. 1999;45:186-190. (Pubitemid 29333766)
161. Ladabaum U, Chey WD, Scheiman JM, et al. Reappraisal of non-invasive management strategies for uninvestigated dyspepsia: a cost-minimization analysis. Aliment Pharmacol Ther. 2002;16:1491-1501. (Pubitemid 34953590)
162. Spiegel B, Vakil N, Ofman J. Dyspepsia management in primary care: a decision analysis of competing strategies. Gastroenterology. 2002;122:1270-1285. (Pubitemid 34465170)
163. Rabeneck L, Souchek J, Wristers K, et al. A double-blind, randomized, placebo-controlled trial of proton pump inhibitor herapy in patients with uninvestigated dyspepsia. Am J Gastroenterol. 2002;97:3045-3051. (Pubitemid 35424574)
164. Talley NJ, Lauritsen K. The potential role of acid suppression in functional dyspepsia: the BOND, OPERA, PILOT, and ENCORE studies. Gut. 2002;50(suppl 4):iv36-iv41. (Pubitemid 34407468)
165. Owens DM, Nelson DK, Talley NJ. The irritable bowel syndrome: long-term prognosis and the physician- patient interaction. Ann Intern Med. 1995;122:107-112.
166. van Kerkhoven LA, van Rossum LG, van Oijen MG, et al. Upper gastrointestinal endoscopy does not reassure patients with functional dyspepsia. Endoscopy. 2006;38:879-885.
167. Elta GH, Behler EM, Colturi TJ. Comparison of coffee intake and coffee-induced symptoms in patients with duodenal ulcer, nonulcer dyspepsia and normal controls. Am J Gastroenterol. 1990;85:1339-1342. (Pubitemid 20360644)
168. Talley NJ, Weaver AL, Zinsmeister AR. Smoking, alcohol, and nonsteroidal anti-inflammatory drugs in outpatients with functional dyspepsia and among dyspepsia subgroups. Am J Gastroenterol. 1994;89:524-528. (Pubitemid 24106217)
169. Moayyedi P, Soo S, Deeks J, et al. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006;4:CD001960.
170. Moayyedi P, Shelly S, Deeks J, et al. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2011;2:CD001960.
171. Moayyedi P, Delaney BC, Vakil N, et al. The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis. Gastroenterology. 2004; 127:1329-1337. (Pubitemid 39457759)
172. McColl KE. Protagonist: should we eradicate Helicobacter pylori in non-ulcer dyspepsia? Gut. 2001;48:759-761. (Pubitemid 32476974)
173. Tack J. Prokinetics and fundic relaxants in upper functional GI disorders. Curr Opin Pharmacol. 2008;8:690-696.
174. Veldhuyzen van Zanten S, Jones M, Verlinden M, et al. Efficacy of cisapride and domperidone in functional (nonulcer) dyspepsia: a meta-analysis. Am J Gastroenterol. 2001; 96:689-696. (Pubitemid 32240716)
175. Hallerbäck BI, Bommelaer G, Bredberg E, et al. Dose finding study of mosapride in functional dyspepsia: a placebocontrolled, randomized study. Aliment Pharmacol Ther. 2002;16:959-967. (Pubitemid 34461766)
176. Sugumar A, Singh A, Pasricha PJ. A systematic review of the efficacy of domperidone for the treatment of diabetic gastroparesis. Clin Gastroenterol Hepatol. 2008;6:726-733.
177. Sanger GJ, Alpers DH. Development of drugs for gastrointestinal motor disorders: translating science to clinical need. Neurogastroenterol Motil. 2008;20:177-184. (Pubitemid 351197401)
178. Sanger GJ. Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases. Drug Discov Today. 2008;13:234-239.
179. Vakil N, Laine L, Talley NJ, et al. Tegaserod treatment for dysmotility-like functional dyspepsia: results of two randomized, controlled trials. Am J Gastroenterol. 2008;103: 1906-1919.
180. Holtmann G, Talley NJ, Liebregts T, et al. A placebocontrolled trial of itopride in functional dyspepsia. N Engl J Med. 2006;354:832-840. (Pubitemid 43290921)
181. Talley NJ, Tack J, Ptak T, et al. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut. 2008;57:740-746. (Pubitemid 351716964)
182. MacLaren R, Kiser TH, Fish DN, et al. Erythromycin vs metoclopramide for facilitating gastric emptying and tolerance to intragastric nutrition in critically ill patients. J Parenter Enteral Nutr. 2008;32:412-419. (Pubitemid 351875941)
183. Moshiree B, McDonald R, Hou W, et al. Comparison of the effect of azithromycin versus erythromycin on antroduodenal pressure profiles of patients with chronic functional gastrointestinal pain and gastroparesis. Dig Dis Sci. 2010;55: 675-683.
184. Ozaki K, Monnai M, Onoma M, et al. Effects of mitemcinal (GM-611), an orally active erythromycin-derived prokinetic agent, on delayed gastric emptying and postprandial glucose in a new minipig model of diabetes. J Diabetes Complications. 2008;22:339-347.
185. Onoma M, Ozaki K, Yogo K, et al. Mitemcinal (GM-611), an orally active motilin receptor agonist, improves delayed gastric emptying in a canine model of diabetic gastroparesis. Clin Exp Pharmacol Physiol. 2008;35:788-796. (Pubitemid 351725240)
186. Sanger GJ, Westaway SM, Barnes AA, et al. GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil. 2009;21:657-664.
187. Tack J, Depoortere I, Bisschops R, et al. Influence of ghrelin on interdigestive gastrointestinal motility in humans. Gut. 2006;55:327-333. (Pubitemid 43268268)
188. Tack J, Depoortere I, Bisschops R, et al. Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment Pharmacol Ther. 2005;22:847-853. (Pubitemid 41568544)
189. Akamizu T, Iwakura H, Ariyasu H, et al. FD Clinical Study Team. Repeated administration of ghrelin to patients with functional dyspepsia: its effects on food intake and appetite. Eur J Endocrinol. 2008;158:491-498. (Pubitemid 351606344)
190. Lasseter KC, Shaughnessy L, Cummings D, et al. Ghrelin agonist (TZP-101): safety, pharmacokinetics and pharmacodynamic evaluation in healthy volunteers: a phase I, firstin- human study. J Clin Pharmacol. 2008;48:193-202.
191. Tack J, Janssen P. Emerging drugs for functional dyspepsia. Expert Opin Emerg Drugs. 2011;16:283-292.
192. Van Oudenhove L, Kindt S, Vos R, et al. Influence of buspirone on gastric sensorimotor function in man. Aliment Pharmacol Ther. 2008;28:1326-1333.
193. Miwa H, Nagahara A, Tominaga K, et al. Efficacy of the 5-HT1A agonist tandospirone citrate in improving symptomsof patients with functional dyspepsia: a randomized controlled trial. Am J Gastroenterol. 2009;104:2779-2787.
194. Suzuki H, Hibi T. Acotiamide (Z-338) as a possible candidate for the treatment of functional dyspepsia. Neurogastroenterol Motil. 2010;22:595-599.
195. Tack J, Janssen P. Acotiamide (Z-338, YM443), a new drug for the treatment of functional dyspepsia. Expert Opin Investig Drugs. 2011;20:701-712.
196. Seto K, Sasaki T, Katsunuma K, et al. Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats. Neurogastroenterol Motil. 2008;20: 1051-1059.
197. Matsunaga Y, Tanaka T, Yoshinaga K, et al. Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging QT interval in dogs: comparison with cisapride, itopride, and mosapride. J Pharmacol Exp Ther. 2011;336:791-800.
198. Tack J, Masclee A, Heading R, et al. A dose-ranging, placebo-controlled, pilot trial of acotiamide in patients with functional dyspepsia. Neurogastroenterol Motil. 2009;21: 272-280.
199. Matsueda K, Hongo M, Tack J, et al. Clinical trial: dosedependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia-100mg t.i.d. is an optimal dosage. Neurogastroenterol Motil. 2010;22: 618-e173.
200. Matsueda K, Hongo M, Tack J, et al. Efficacy and safety of acotiamide (Z-338) administered orally for 4-weeks in patients with functional dyspepsia: results from a randomized, doubleblind, placebo-controlled phase III trial in Japan. Gastroenterology. 2011;140:S30.
201. Matsueda K, Hongo M, Tack J, et al. Efficacy of acotiamide (Z-338) in patients with postprandial distress syndrome or overlap of epigastric pain syndrome and postprandial distress syndrome in functional dyspepsia. Gastroenterology. 2011;140:S805.
202. Madsen JL, Fuglsang SA. Randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans. Aliment Pharmacol Ther. 2008;27:609-615. (Pubitemid 351316787)
203. Talley NJ, Choung RS, Camilleri M, et al. Asimadoline, a kappa-opioid agonist, and satiation in functional dyspepsia. Aliment Pharmacol Ther. 2008;27:1122-1131. (Pubitemid 351614887)
204. Passos Mdo C, Duro D, Fregni F. CNS or classic drugs for the treatment of pain in functional dyspepsia? A systematic review and meta-analysis of the literature. Pain Physician. 2008;11:597-609.
205. van Kerkhoven LA, Laheij RJ, Aparicio N, et al. Effect of the antidepressant venlafaxine in functional dyspepsia: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2008;6:746-752.
206. Van Oudenhove L, Tack J. Is the antidepressant venlafaxine effective for the treatment of functional dyspepsia? Nat Clin Pract Gastroenterol Hepatol. 2009;6:74-75.
207. Hashash JG, Abdul-Baki H, Azar C, et al. Clinical trial: a randomized controlled cross-over study of flupenthixol+ melitracen in functional dyspepsia. Aliment Pharmacol Ther. 2008;27:1148-1155. (Pubitemid 351614888)
208. Rosch W, Liebregts T, Gundermann KJ, et al. Phytotherapy for functional dyspepsia: a review of the clinical evidence for the herbal preparation STW5. Phytomedicine. 2006;13(suppl 5): 114-121. (Pubitemid 44816468)
209. Braden B, Caspary W, Borner N, et al. Clinical effects of STW 5 (Iberogast) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis. Neurogastroenterol Motil. 2009;21:632-638.
210. Soo S, Moayyedi P, Deeks JJ, et al. Psychological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2011;2:CD002301.