Functional Gastroduodenal Disorders

A numerically important group of patients with functional gastrointestinal disorders have chronic symptoms that can be attributed to the gastroduodenal region. Based on the consensus opinion of an international panel of clinical investigators who reviewed the available evidence, a classification of the functional gastroduodenal disorders is proposed. Four categories of functional gastroduodenal disorders are distinguished. The first category, functional dyspepsia, groups patients with symptoms thought to originate from the gastroduodenal region, specifically epigastric pain or burning, postprandial fullness, or early satiation. Based on recent evidence and clinical experience, a subgroup classification is proposed for postprandial distress syndrome (early satiation or postprandial fullness) and epigastric pain syndrome (pain or burning in the epigastrium). The second category, belching disorders, comprises aerophagia (troublesome repetitive belching with observed excessive air swallowing) and unspecified belching (no evidence of excessive air swallowing). The third category, nausea and vomiting disorders, comprises chronic idiopathic nausea (frequent bothersome nausea without vomiting), functional vomiting (recurrent vomiting in the absence of self-induced vomiting, or underlying eating disorders, metabolic disorders, drug intake, or psychiatric or central nervous system disorders), and cyclic vomiting syndrome (stereotypical episodes of vomiting with vomiting-free intervals). The rumination syndrome is a fourth category of functional gastroduodenal disorder characterized by effortless regurgitation of recently ingested food into the mouth followed by rechewing and reswallowing or expulsion. The proposed classification requires further research and careful validation but the criteria should be of value for clinical practice; for epidemiological, pathophysiological, and clinical management studies; and for drug development. A numerically important group of patients with functional gastrointestinal disorders have chronic symptoms that can be attributed to the gastroduodenal region. Based on the consensus opinion of an international panel of clinical investigators who reviewed the available evidence, a classification of the functional gastroduodenal disorders is proposed. Four categories of functional gastroduodenal disorders are distinguished. The first category, functional dyspepsia, groups patients with symptoms thought to originate from the gastroduodenal region, specifically epigastric pain or burning, postprandial fullness, or early satiation. Based on recent evidence and clinical experience, a subgroup classification is proposed for postprandial distress syndrome (early satiation or postprandial fullness) and epigastric pain syndrome (pain or burning in the epigastrium). The second category, belching disorders, comprises aerophagia (troublesome repetitive belching with observed excessive air swallowing) and unspecified belching (no evidence of excessive air swallowing). The third category, nausea and vomiting disorders, comprises chronic idiopathic nausea (frequent bothersome nausea without vomiting), functional vomiting (recurrent vomiting in the absence of self-induced vomiting, or underlying eating disorders, metabolic disorders, drug intake, or psychiatric or central nervous system disorders), and cyclic vomiting syndrome (stereotypical episodes of vomiting with vomiting-free intervals). The rumination syndrome is a fourth category of functional gastroduodenal disorder characterized by effortless regurgitation of recently ingested food into the mouth followed by rechewing and reswallowing or expulsion. The proposed classification requires further research and careful validation but the criteria should be of value for clinical practice; for epidemiological, pathophysiological, and clinical management studies; and for drug development. A large group of patients with functional gastrointestinal disorders have chronic symptoms that can be attributed to the gastroduodenal region (Table 1). Based on the consensus opinion of an international panel of clinical investigators who reviewed the available evidence, a classification of the functional gastroduodenal disorders into functional dyspepsia (FD) (category B1, comprising postprandial distress syndrome [PDS] and epigastric pain syndrome [EPS]), belching disorders (category B2, comprising aerophagia and unspecified belching), functional nausea and vomiting disorders (category B3, comprising chronic idiopathic nausea [CIN], functional vomiting, and cyclic vomiting syndrome [CVS]), and the rumination syndrome (category B4) is recommended.Table 1Functional Gastrointestinal DisordersB. Functional gastroduodenal disorders B1. Functional dyspepsia B1a. Postprandial distress syndrome B1b. Epigastric pain syndrome B2. Belching disorders B2a. Aerophagia B2b. Unspecified excessive belching B3. Nausea and vomiting disorders B3a. Chronic idiopathic nausea B3b. Functional vomiting B3c. Cyclic vomiting syndrome B4. Rumination syndrome in adults Open table in a new tab B1. Functional DyspepsiaDefinition of Functional DyspepsiaMany different sets of symptoms have been used synonymously with the term dyspepsia, which has caused confusion. Most patients do not recognize the term dyspepsia, and historically physicians have interpreted the meaning of dyspepsia very variably.Hence, the committee recommended the following pragmatic definition: FD is defined as the presence of symptoms thought to originate in the gastroduodenal region, in the absence of any organic, systemic, or metabolic disease that is likely to explain the symptoms. These symptoms are listed in Table 2. However, particularly for experimental purposes, the term functional dyspepsia should preferably be replaced by more distinctively defined disorders, for which there is now increasing evidence in the literature. These are the new diagnostic categories of (1) meal-induced dyspeptic symptoms (PDS), and (2) epigastric pain (EPS).Table 2Dyspeptic symptoms and their definitionsSymptomDefinitionEpigastric painEpigastric refers to the region between the umbilicus and lower end of the sternum, and marked by the midclavicular lines. Pain refers to a subjective, unpleasant sensation; some patients may feel that tissue damage is occurring. Other symptoms may be extremely bothersome without being interpreted by the patient as pain.Epigastric burningEpigastric refers to the region between the umbilicus and lower end of the sternum, and marked by the midclavicular lines. Burning refers to an unpleasant subjective sensation of heat.Postprandial fullnessAn unpleasant sensation like the prolonged persistence of food in the stomachEarly satiationA feeling that the stomach is overfilled soon after starting to eat, out of proportion to the size of the meal being eaten, so that the meal cannot be finished. Previously, the term “early satiety” was used, but satiation is the correct term for the disappearance of the sensation of appetite during food ingestion. Open table in a new tab Patients with 1 or more of these symptoms (postprandial fullness, early satiation, or epigastric pain or burning) are referred to as patients with dyspepsia. Previous Rome committees defined dyspepsia as pain or discomfort centered in the upper abdomen and excluded reflux symptoms.1Talley N.J. Stanghellini V Heading R.C. Koch K.L. Malagelada J.R. Tytgat G.N.J. Functional gastroduodenal disorders.Gut. 1999; 45: 37-42Google Scholar However, it has remained unsettled whether discomfort is a mild variant of pain or a separate symptom complex.1Talley N.J. Stanghellini V Heading R.C. Koch K.L. Malagelada J.R. Tytgat G.N.J. Functional gastroduodenal disorders.Gut. 1999; 45: 37-42Google Scholar, 2Stanghellini V. Review article pain versus discomfort—is differentiation clinically useful?.Aliment Pharmacol Ther. 2001; 15: 145-149Crossref PubMed Scopus (33) Google Scholar Moreover, discomfort comprised a large number of nonpainful symptoms including upper abdominal fullness, early satiety, bloating, or nausea. Bloating is an unpleasant sensation of tightness and should be distinguished from visible distention; usually, this symptom is not well localized and often occurs in IBS so bloating was not considered a cardinal symptom of dyspepsia. Nausea (queasiness or sick sensation or a feeling of the need to vomit) may occur with dyspepsia or IBS but is often from central origin and is also not considered a localizing symptom.1Talley N.J. Stanghellini V Heading R.C. Koch K.L. Malagelada J.R. Tytgat G.N.J. Functional gastroduodenal disorders.Gut. 1999; 45: 37-42Google Scholar, 2Stanghellini V. Review article pain versus discomfort—is differentiation clinically useful?.Aliment Pharmacol Ther. 2001; 15: 145-149Crossref PubMed Scopus (33) Google Scholar, 3Colin-Jones D.G. Bloom B. Bodemar G. Crean G. Freston J. Gugler R. Malagelada J. Nyren O. Petersen H. Piper D. Management of dyspepsia report of a working party.Lancet. 1988; 1: 576-579PubMed Google Scholar, 4Talley N.J. Weaver A.L. Tesmer D.L. Zinsmeister A.R. Lack of discriminant value of dyspepsia subgroups in patients referred for upper endoscopy.Gastroenterology. 1993; 105: 1378-1386Abstract Full Text PDF PubMed Scopus (230) Google Scholar Whether or not individual symptoms such as upper abdominal fullness or bloating are labeled as pain by the patient may depend on cultural and linguistic factors and possibly education level.2Stanghellini V. Review article pain versus discomfort—is differentiation clinically useful?.Aliment Pharmacol Ther. 2001; 15: 145-149Crossref PubMed Scopus (33) Google ScholarHeartburn has been defined by the esophageal committee. A burning sensation confined to the epigastrium is not considered to be heartburn unless it also radiates retrosternally. In the past, heartburn (as well as acid regurgitation) has often been included as sufficient on its own to define dyspepsia.3Colin-Jones D.G. Bloom B. Bodemar G. Crean G. Freston J. Gugler R. Malagelada J. Nyren O. Petersen H. Piper D. Management of dyspepsia report of a working party.Lancet. 1988; 1: 576-579PubMed Google Scholar Heartburn is not considered a symptom that primarily arises from the gastroduodenum, and there is evidence that heartburn has moderate specificity for gastroesophageal reflux disease (GERD).4Talley N.J. Weaver A.L. Tesmer D.L. Zinsmeister A.R. Lack of discriminant value of dyspepsia subgroups in patients referred for upper endoscopy.Gastroenterology. 1993; 105: 1378-1386Abstract Full Text PDF PubMed Scopus (230) Google Scholar, 5Klauser A.G. Schindlbeck N.E. Muller-Lissner S.A. Symptoms in gastro-esophageal reflux disease.Lancet. 1990; 335: 205-208Abstract PubMed Scopus (699) Google Scholar Hence, the committee concluded that heartburn is excluded from the definition of dyspepsia even though it may occur simultaneously with gastroduodenal symptoms. Similarly, retrosternal pain suggestive of esophageal disease or of a type embraced by the term noncardiac chest pain is excluded from dyspepsia.Uninvestigated versus investigated dyspepsiaEspecially when considering epidemiological data, it is important to distinguish the subjects with dyspeptic symptoms who have not been investigated from patients with a diagnostic label after investigation, with or without an identified causal abnormality.Organic versus idiopathic dyspepsiaFrom an etiological viewpoint, patients with dyspeptic symptoms can be subdivided into 2 main categories: 1Those with an identified organic or metabolic cause for the symptoms where, if the disease improves or is eliminated, symptoms also improve or resolve (eg, peptic ulcer disease, GERD with or without esophagitis, malignancy, pancreaticobiliary disease, or medication use).2Those with no identifiable explanation for the symptoms. In some of these patients, an identifiable pathophysiological or microbiologic abnormality of uncertain clinical relevance (eg, Helicobacter pylori gastritis) may be present, which is not thought to explain the symptoms. Others have abnormal motor or sensory dysfunction (eg, altered gastric emptying, fundic dysaccommodation, or gastroduodenal hypersensitivity) of uncertain significance. This broad group of patients with idiopathic dyspepsia has previously been referred to as nonulcer dyspepsia, essential dyspepsia, idiopathic dyspepsia, or FD. FD is currently the most recognized term in the literature.EpidemiologyApproximately 20% to 30% of people in the community each year report chronic or recurrent dyspeptic symptoms.6Talley N.J. Zinsmeister A.R. Schleck C.D. et al.Dyspepsia and dyspepsia subgroups a population based study.Gastroenterology. 1992; 102: 1259-1268PubMed Google Scholar, 7Agreus 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: 671-680Abstract Full Text PDF PubMed Scopus (630) Google Scholar Although these data represent uninvestigated dyspepsia and often also included heartburn, an organic cause is found in only a minority of dyspeptic subjects who are investigated, and hence it is reasonable to assume that the majority would have functional dyspepsia.8Johnsen R. Bernersen B. Straume B. et al.Prevalence of endoscopic and histological findings in subjects with and without dyspepsia.BMJ. 1991; 302: 749-752Crossref PubMed Scopus (211) Google Scholar, 9Klauser A.G. Voderholzer W.A. Knesewitsch P.A. et al.What is behind dyspepsia?.Dig Dis Sci. 1993; 38: 147-154Crossref PubMed Scopus (118) Google Scholar Based on prospective studies of subjects who report dyspeptic symptoms for the first time, the incidence is approximately 1% per year.7Agreus 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: 671-680Abstract Full Text PDF PubMed Scopus (630) Google Scholar, 10Talley N.J. Weaver A.L. Zinsmeister A.R. et al.Onset and disappearance of gastrointestinal symptoms and functional gastrointestinal disorders.Am J Epidemiol. 1992; 136: 165-177PubMed Google Scholar The majority of patients with unexplained dyspeptic symptoms continue to be symptomatic over the long-term despite periods of remission.11Talley N.J. McNeil D. Hayden A. et al.Prognosis of chronic unexplained dyspepsia. A prospective study of potential predictor variables in patients with endoscopically diagnosed nonulcer dyspepsia.Gastroenterology. 1987; 92: 1060-1066PubMed Scopus (70) Google Scholar Approximately, 1 in 2 subjects is estimated to seek health care for their dyspeptic symptoms at some time in their life.12Koloski N.A. Talley N.J. Boyce P.M. 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: 1340-1349Crossref PubMed Google Scholar Pain severity and anxiety (including fear of serious disease) appear to be factors associated with consulting behavior.12Koloski N.A. Talley N.J. Boyce P.M. 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: 1340-1349Crossref PubMed Google Scholar, 13Talley N.J. Boyce P. Jones M. Dyspepsia and health care seeking in a community how important are psychological factors?.Dig Dis Sci. 1998; 43: 1016-1022Crossref PubMed Scopus (77) Google ScholarHeterogeneity of FD Symptoms: SubgroupsIt seems likely that chronic unexplained dyspepsia includes different types of patients with distinct underlying pathophysiologies who require different management approaches. However, it has been particularly difficult to identify these subgroups reliably. Subclasses based on symptom clusters have been proposed.6Talley N.J. Zinsmeister A.R. Schleck C.D. et al.Dyspepsia and dyspepsia subgroups a population based study.Gastroenterology. 1992; 102: 1259-1268PubMed Google Scholar, 14Drossman D.A. Thompson G.W. Talley N.J. Funch-Jensen P. Janssens J. Whitehead W.E. Identification of subgroups of functional gastrointestinal disorders.Gastroenterol Int. 1990; 3: 159-172Google Scholar In clinical practice, however, this classification showed great overlap between subclasses, limiting its value.7Agreus 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: 671-680Abstract Full Text PDF PubMed Scopus (630) Google Scholar, 15Stanghellini V. Tosetti C. Paternicoá A. et al.Predominant symptoms identify different subgroups in functional dyspepsia.Am J Gastroenterol. 1999; 94: 2080-2085Crossref PubMed Scopus (106) Google ScholarIdentifying the predominant symptom was shown to distinguish subgroups with different demographic and symptomatic properties and with some relationship to putative pathophysiological mechanisms like delayed gastric emptying and presence of H pylori.15Stanghellini V. Tosetti C. Paternicoá A. et al.Predominant symptoms identify different subgroups in functional dyspepsia.Am J Gastroenterol. 1999; 94: 2080-2085Crossref PubMed Scopus (106) Google Scholar Thus, the Rome II committee proposed a subdivision according to the predominant symptom being pain or discomfort, but this subdivision has also been criticized because of the difficulty distinguishing pain from discomfort, the lack of an accepted definition of the term predominant, number of patients who do not fit into one of the subgroups, and especially the lack of stability, even over short time periods.4Talley N.J. Weaver A.L. Tesmer D.L. Zinsmeister A.R. Lack of discriminant value of dyspepsia subgroups in patients referred for upper endoscopy.Gastroenterology. 1993; 105: 1378-1386Abstract Full Text PDF PubMed Scopus (230) Google Scholar, 7Agreus 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: 671-680Abstract Full Text PDF PubMed Scopus (630) Google Scholar, 16Laheij R.J. De Koning R.W. Horrevorts A.M. Rongen R.J. Rossum L.G. Witteman E.M. Hermsen J.T. Jansen J.B. Predominant symptom behavior in patients with persistent dyspepsia during treatment.J Clin Gastroenterol. 2004; 38: 490-495Crossref PubMed Scopus (27) Google ScholarA different approach was based on attempts to identify pathophysiology-based subgroups. Thus, associations were shown between symptom patterns and delayed gastric emptying,17Stanghellini V. Tosetti C. Paternico A. et al.Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia.Gastroenterology. 1996; 110: 1036-1042Abstract Full Text Full Text PDF PubMed Scopus (556) Google Scholar, 18Perri F. Clemente R. Festa V. Annese V. Quitadamo M. Rutgeerts P. Andriulli A. Patterns of symptoms in functional dyspepsia role of Helicobacter pylori infection and delayed gastric emptying.Am J Gastroenterol. 1998; 93: 2082-2088Crossref PubMed Scopus (120) Google Scholar, 19Sarnelli G. Caenepeel P. Geypens B. Janssens J. Tack J. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia.Am J Gastroenterol. 2003; 98: 783-788Crossref PubMed Scopus (406) Google Scholar impaired fundic accommodation,20Tack J. Piessevaux H. Coulie B. Caenepeel P. Janssens J. Role of impaired gastric accommodation to a meal in functional dyspepsia.Gastroenterology. 1998; 115: 1346-1352Abstract Full Text Full Text PDF PubMed Scopus (899) Google Scholar and visceral hypersensitivity.21Tack J. Caenepeel P. Fischler B. Piessevaux H. Janssens J. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia.Gastroenterology. 2001; 121: 526-535Abstract Full Text Full Text PDF PubMed Scopus (461) Google Scholar However, the association of these pathophysiological mechanisms with symptoms has not been confirmed in other studies.22Boeckxstaens G.E. Hirsch D.P. Kuiken S.D. Heisterkamp S.H. Tytgat G.N. The proximal stomach and postprandial symptoms in functional dyspeptics.Am J Gastroenterol. 2002; 97: 40-48Crossref PubMed Google Scholar, 23Rhee P.L. Kim Y.H. Son H.J. Kim J.J. Koh K.C. Paik S.W. Rhee J.C. Choi K.W. Evaluation of individual symptoms cannot predict presence of gastric hypersensitivity in functional dyspepsia.Dig Dis Sci. 2000; 45: 1680-1684Crossref PubMed Scopus (39) Google Scholar, 24Talley N.J. Verlinden M. Jones M. Can symptoms discriminate among those with delayed or normal gastric emptying in dysmotility-like dyspepsia?.Am J Gastroenterol. 2001; 96: 1422-1428Crossref PubMed Google ScholarDiagnostic CriteriaThe committee proposed to define FD at 2 levels. A general, more umbrella definition of FD, to be used mainly for clinical purposes, and although further research on more specific definitions is ongoing, is provided under category B1. However, particularly for pathophysiological and therapeutic research purposes, newly defined entities of (1) meal-induced dyspeptic symptoms (PDS, defined under category B1a), and (2) epigastric pain (EPS, defined under category B1b), should be used operatively. B1. Diagnostic Criteria ⁎Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis for Functional DyspepsiaMust include 1One or more of: aBothersome postprandial fullnessbEarly satiationcEpigastric paindEpigastric burningAND2No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptomsB1a. Diagnostic Criteria ⁎Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis for Postprandial Distress SyndromeMust include one or both of the following: 1Bothersome postprandial fullness, occurring after ordinary sized meals, at least several times per week2Early satiation that prevents finishing a regular meal, at least several times per weekSupportive criteria 1Upper abdominal bloating or postprandial nausea or excessive belching can be present2EPS may coexist B1b. Diagnostic Criteria ⁎Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis for Epigastric Pain SyndromeMust include all of the following: 1Pain or burning localized to the epigastrium of at least moderate severity at least once per week2The pain is intermittent3Not generalized or localized to other abdominal or chest regions4Not relieved by defecation or passage of flatus5Not fulfilling criteria for gallbladder and sphincter of Oddi disordersSupportive criteria 1The pain may be of a burning quality but without a retrosternal component2The pain is commonly induced or relieved by ingestion of a meal but may occur while fasting3Postprandial distress syndrome may coexist Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosisOverlap with GERD and IBSHeartburn, considered an esophageal symptom, as well as dyspepsia are extremely common, and some overlap between both is likely. The Rome II definition proposed to exclude patients with predominant heartburn from the dyspepsia spectrum,1Talley N.J. Stanghellini V Heading R.C. Koch K.L. Malagelada J.R. Tytgat G.N.J. Functional gastroduodenal disorders.Gut. 1999; 45: 37-42Google Scholar but recent studies have shown that the predominant symptom approach does not reliably identify all patients with GERD.25Peura D.A. Kovacs T.O. Metz D.C. Siepman N. Pilmer B.L. Talley N.J. Lansoprazole in the treatment of functional dyspepsia two double-blind, randomized, placebo-controlled trials.Am J Med. 2004; 116: 740-748Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 26Tack J. Caenepeel P. Arts J. Lee K.J. Sifrim D. Janssens J. Prevalence and symptomatic impact of non-erosive reflux disease in functional dyspepsia.Gut. 2005; 54: 1370-1376Crossref PubMed Scopus (130) Google Scholar, 27Carlsson R. Dent J. Bolling-Sternevald E. et al.The usefulness of a structured questionnaire in the assessment of symptomatic gastroesophageal reflux disease.Scand J Gastroenterol. 1998; 33: 1023-1029Crossref PubMed Scopus (415) Google Scholar, 28Moayyedi P. Delaney B.C. Vakil N. Forman D. Talley N.J. The efficacy of proton pump inhibitors in nonulcer dyspepsia a systematic review and economic analysis.Gastroenterology. 2004; 127: 1329-1337Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar In general, overlap of GERD with PDS or EPS is probably frequent and needs to be carefully considered in both clinical practice and experimental trials. The committee recommends that the presence of frequent and typical reflux symptoms should lead to a provisional diagnosis of GERD.29Thomson A.B. Barkun A.N. Armnstrong D. Chiba N. White R.J. Daniels S. Escobedo S. Chakraborty B. Sinclair P. Van Zanten S.J. The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia The Canadian Adult Dyspepsia Empiric Treatment–Prompt Endoscopy (CADET-PE) study.Aliment Pharmacol Ther. 2003; 17: 1481-1491Crossref PubMed Scopus (232) Google Scholar In clinical practice and for clinical trials, recognition of frequent heartburn may be improved by a simple descriptive questionnaire.26Tack J. Caenepeel P. Arts J. Lee K.J. Sifrim D. Janssens J. Prevalence and symptomatic impact of non-erosive reflux disease in functional dyspepsia.Gut. 2005; 54: 1370-1376Crossref PubMed Scopus (130) Google Scholar, 27Carlsson R. Dent J. Bolling-Sternevald E. et al.The usefulness of a structured questionnaire in the assessment of symptomatic gastroesophageal reflux disease.Scand J Gastroenterol. 1998; 33: 1023-1029Crossref PubMed Scopus (415) Google Scholar The presence of heartburn does not exclude a diagnosis of PDS or EPS if dyspepsia persists despite a trial of adequate acid suppression therapy.Overlap between dyspeptic symptoms and IBS is also commonly observed, and overlap between IBS on one hand and PDS or EPS on the other hand is likely to occur. The presence of IBS does not exclude the diagnosis of any of these functional gastroduodenal disorders because coexisting IBS was found to have a minor impact on symptom pattern and putative pathophysiological mechanisms in FD.30Corsetti M. Caenepeel P. Fischler B. Janssens J. Tack J. Impact of coexisting irritable bowel syndrome on symptoms and pathophysiological mechanisms in functional dyspepsia.Am J Gastroenterol. 2004; 99: 1152-1159Crossref PubMed Scopus (148) Google ScholarRationale for Changes in Criteria From Rome IIThe rationale for the proposed new classification was based on the inadequacy of prior approaches such as the predominant symptom, the results of factor analysis in tertiary care and in the general population, clinical experience, and new observations in the peer-reviewed literature. Previously, all patients without definite structural or biochemical explanation for dyspeptic symptoms were considered to have functional dyspepsia. The committee agreed that there is a lack of uniform interpretation and acceptance of the term FD at different levels of practice, in different countries and with regulatory authorities. Despite the Rome II recommendations, several recent large studies included heartburn and even acid regurgitation as “typical symptoms of dyspepsia.”25Peura D.A. Kovacs T.O. Metz D.C. Siepman N. Pilmer B.L. Talley N.J. Lansoprazole in the treatment of functional dyspepsia two double-blind, randomized, placebo-controlled trials.Am J Med. 2004; 116: 740-748Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 28Moayyedi P. Delaney B.C. Vakil N. Forman D. Talley N.J. The efficacy of proton pump inhibitors in nonulcer dyspepsia a systematic review and economic analysis.Gastroenterology. 2004; 127: 1329-1337Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 31Talley N.J. Meineche-Schmidt V. Pare P. Duckworth M. Raisanen P. Pap A. Kordecki H. Schmid V. Efficacy of omeprazole in functional dyspepsia double-blind, randomized, placebo-controlled trials (the Bond and Opera studies).Aliment Pharmacol Ther. 1998; 12: 1055-1065Crossref PubMed Scopus (353) Google ScholarThere is also increasing evidence for the existence of different entities within the “dyspepsia symptom complex.” There is no single symptom that is present in all patients with FD, and there is considerable variation in the symptom pattern between patients.32Tack J. Bisschops R. Sarnelli G. Pathophysiology and treatment of functional dyspepsia.Gastroenterology. 2004; 127: 1239-1255Abstract Full Text Full Text PDF PubMed Scopus (406) Google Scholar Factor analysis studies in the general population and in patients with idiopathic dyspeptic symptoms7Agreus L. Svardsudd K. 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