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• W2057000827 abstract "The role of delayed gastric emptying in generating symptoms in functional and motor disorders of the upper gastrointestinal (GI) tract is a long-standing issue of controversy.1Talley N.J. Locke 3rd, G.R. Tack J. Does delayed gastric emptying really cause symptoms in functional dyspepsia? We still doubt it!.Gut. 2006; 55: 1674Crossref PubMed Scopus (11) Google Scholar Closely related to this issue, the distinction between idiopathic gastroparesis and functional dyspepsia (FD) with delayed gastric emptying is also an unsettled issue.2Talley 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 Scholar, 3Karamanolis G. Caenepeel P. Arts J. et al.Determinants of symptom pattern in idiopathic severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction?.Gut. 2007; 56: 29-36Crossref PubMed Scopus (103) Google Scholar The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) gastroparesis clinical consortium, a multicenter collaborative network that included patients with gastroparesis in a registry, reported on the largest idiopathic gastroparesis data set to date in the January 2011 issue of Gastroenterology.4Parkman H.P. Yates K. Hasler W.L. et al.National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research ConsortiumClinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.Gastroenterology. 2011; 140: 101-115Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar Besides its numerical superiority, the NIDDK data set draws on a number of strengths including the prospective collection of data, the use of well-validated questionnaires for upper GI symptom severity, and the use of a standardized gastric emptying test with well-established cutoff.4Parkman H.P. Yates K. Hasler W.L. et al.National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research ConsortiumClinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.Gastroenterology. 2011; 140: 101-115Abstract Full Text Full Text PDF PubMed Scopus (216) Google ScholarIn our opinion, the NIDDK report does not strengthen the case for considering idiopathic gastroparesis an entity that is clearly distinct from FD (with delayed emptying). The symptom pattern of the idiopathic gastroparesis NIDDK cohort is highly reminiscent of FD and, in fact, 91% of patients fulfilled the Rome III criteria for FD/postprandial distress syndrome.5Tack J. Talley N.J. Camilleri M. et al.Functional gastroduodenal disorders.Gastroenterology. 2006; 130: 1466-1479Abstract Full Text Full Text PDF PubMed Scopus (1412) Google Scholar The recent Rome III consensus proposed to make a distinction between FD symptoms, and nausea and vomiting disorders, because the symptoms of nausea and vomiting have been associated with the presence of delayed gastric emptying in large patient cohorts.5Tack J. Talley N.J. Camilleri M. et al.Functional gastroduodenal disorders.Gastroenterology. 2006; 130: 1466-1479Abstract Full Text Full Text PDF PubMed Scopus (1412) Google Scholar However, only 34% of the NIDDK consortium patients fulfilled criteria for chronic idiopathic nausea.4Parkman H.P. Yates K. Hasler W.L. et al.National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research ConsortiumClinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.Gastroenterology. 2011; 140: 101-115Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar With the highest symptom ratings in the NIDDK cohort for the cardinal FD symptoms (feelings of stomach fullness, inability to finish a meal, and feeling excessively full after a meal), the current cohort confirms that this symptom pattern does not allow to predict delayed gastric emptying or vice versa.2Talley 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 Scholar An acute and presumed postinfectious origin, which was present in a large subset of the idiopathic gastroparesis patients, has also been reported in FD and is associated with a higher prevalence of nausea and vomiting.6Tack J. Demedts I. Dehondt G. et al.Clinical and pathophysiological characteristics of acute-onset functional dyspepsia.Gastroenterology. 2002; 122: 1738-1747Abstract Full Text Full Text PDF PubMed Scopus (230) Google ScholarAmong physicians as well as regulatory authorities, “gastroparesis” is often considered a diagnosis more relevant, more worthy of treatment, and more “serious” than FD. This is closely associated with the assumption that gastroparesis is caused by neuromuscular dysfunction in the upper GI tract, whereas in FD, like in other functional disorders, psychosocial factors and psychiatric comorbidity are likely to play a major pathophysiologic role.7Tack 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 However, in the current cohort, high levels of anxiety and depression were found, anxiety and depression were significantly associated with the symptom severity, and depression was among the factors that was independently associated with symptom severity as assessed by the gastroparesis cardinal symptom index.4Parkman H.P. Yates K. Hasler W.L. et al.National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research ConsortiumClinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.Gastroenterology. 2011; 140: 101-115Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar These findings are highly reminiscent of FD, where symptom severity is also determined by depression, as well as “somatization,” which was not assessed in the current cohort.8Van Oudenhove L. Vandenberghe J. Geeraerts B. et al.Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation?.Gut. 2008; 57: 1666-1673Crossref PubMed Scopus (151) Google Scholar Hence, idiopathic gastroparesis symptom severity is also majorly influenced by psychological comorbidities.Measuring gastric emptying in upper GI symptoms reminiscent of gastroparesis or FD might be relevant if it determined symptom severity or treatment outcomes. Increasing delays in the gastric emptying rate were associated with higher severity scores for nausea, vomiting, and loss of appetite. Similar findings have been reported in FD, and in FD with delayed emptying, and in these patients, better correlations were found between symptom severity and pattern and other aspects of gastric sensorimotor function such as hypersensitivity to gastric distention or impaired gastric accommodation.3Karamanolis G. Caenepeel P. Arts J. et al.Determinants of symptom pattern in idiopathic severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction?.Gut. 2007; 56: 29-36Crossref PubMed Scopus (103) Google Scholar, 7Tack 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 In the current cohort, and similar to previous observations,3Karamanolis G. Caenepeel P. Arts J. et al.Determinants of symptom pattern in idiopathic severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction?.Gut. 2007; 56: 29-36Crossref PubMed Scopus (103) Google Scholar the relation between overall symptom severity and delayed emptying was poor. In fact, gastric retention at 2 and 4 hours did not differ between mild, compensated gastroparesis and gastric failure patients, and when overall symptom severity was quantified based on the gastroparesis cardinal symptom index, gastric retention was a risk factor of marginal importance compared with the presence of depression and migraine headaches. Finally, there is a broad body of literature that has established that the presence and severity of delayed gastric emptying, and the improvement under therapy, do not predict symptomatic responsiveness to prokinetic therapy.9Tack J. Prokinetics and fundic relaxants in upper functional gastrointestinal disorders.Curr Opin Pharmacol. 2008; 8: 690-696Crossref PubMed Scopus (110) Google Scholar, 10Arts J. Caenepeel P. Verbeke K. et al.Influence of erythromycin on gastric emptying and meal related symptoms in functional dyspepsia with delayed gastric emptying.Gut. 2005; 54: 455-460Crossref PubMed Scopus (115) Google ScholarBased on symptom associations and treatment impact in the present and previous studies, it seems not more justified to distinguish idiopathic gastroparesis from FD as it would be to distinguish idiopathic impaired accommodation or idiopathic gastric hypersensitivity.7Tack 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 It seems that the existence of a separate nomenclature for idiopathic gastroparesis has more to do with the fact that delayed emptying was historically the first hypothesis to be addressed in unexplained upper GI symptoms, and with the widespread availability of gastric emptying testing, than with its relevance to clinical management.It is in the interest of clinicians dealing with patients with upper GI dysmotility-like symptoms, of regulatory agencies, and of the pharmaceutical industry developing prokinetic drugs to find a way forward from the ill-defined and artificial distinction between FD with delayed emptying and idiopathic gastroparesis. In the past, higher cutoffs for delayed emptying or confirmation of delayed emptying on ≥2 separate gastric emptying tests have been proposed as measures to identify idiopathic gastroparesis, but this has not been based on solid evidence.9Tack J. Prokinetics and fundic relaxants in upper functional gastrointestinal disorders.Curr Opin Pharmacol. 2008; 8: 690-696Crossref PubMed Scopus (110) Google Scholar, 10Arts J. Caenepeel P. Verbeke K. et al.Influence of erythromycin on gastric emptying and meal related symptoms in functional dyspepsia with delayed gastric emptying.Gut. 2005; 54: 455-460Crossref PubMed Scopus (115) Google Scholar Resolving the issue requires analysis of large patient samples, and the NIDDK cohort seems an ideal vehicle to do so. It remains conceivable that a subgroup of patients have characteristics or symptoms that are more clearly driven by delayed gastric emptying, and we speculate that the main candidate features could be the presence of weight loss or the need for nutritional support. Conversely, it is conceivable that elimination of patients based on certain features, for instance being overweight and potentially some psychosocial features, leads to identification of a subgroup that would justify the label “idiopathic gastroparesis.” Until then, “idiopathic gastroparesis” in our opinion equals “FD with delayed gastric emptying”: We believe that idiopathic gastroparesis should be considered at best a candidate mechanism contributing to unexplained upper GI symptoms (FD), rather than a separate “disease entity,” “disorder,” or “syndrome.” Moreover, based on empirical evidence, including the present NIDDK study, its importance as a mechanism may well be modest. The role of delayed gastric emptying in generating symptoms in functional and motor disorders of the upper gastrointestinal (GI) tract is a long-standing issue of controversy.1Talley N.J. Locke 3rd, G.R. Tack J. Does delayed gastric emptying really cause symptoms in functional dyspepsia? We still doubt it!.Gut. 2006; 55: 1674Crossref PubMed Scopus (11) Google Scholar Closely related to this issue, the distinction between idiopathic gastroparesis and functional dyspepsia (FD) with delayed gastric emptying is also an unsettled issue.2Talley 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 Scholar, 3Karamanolis G. Caenepeel P. Arts J. et al.Determinants of symptom pattern in idiopathic severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction?.Gut. 2007; 56: 29-36Crossref PubMed Scopus (103) Google Scholar The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) gastroparesis clinical consortium, a multicenter collaborative network that included patients with gastroparesis in a registry, reported on the largest idiopathic gastroparesis data set to date in the January 2011 issue of Gastroenterology.4Parkman H.P. Yates K. Hasler W.L. et al.National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research ConsortiumClinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.Gastroenterology. 2011; 140: 101-115Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar Besides its numerical superiority, the NIDDK data set draws on a number of strengths including the prospective collection of data, the use of well-validated questionnaires for upper GI symptom severity, and the use of a standardized gastric emptying test with well-established cutoff.4Parkman H.P. Yates K. Hasler W.L. et al.National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research ConsortiumClinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.Gastroenterology. 2011; 140: 101-115Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar In our opinion, the NIDDK report does not strengthen the case for considering idiopathic gastroparesis an entity that is clearly distinct from FD (with delayed emptying). The symptom pattern of the idiopathic gastroparesis NIDDK cohort is highly reminiscent of FD and, in fact, 91% of patients fulfilled the Rome III criteria for FD/postprandial distress syndrome.5Tack J. Talley N.J. Camilleri M. et al.Functional gastroduodenal disorders.Gastroenterology. 2006; 130: 1466-1479Abstract Full Text Full Text PDF PubMed Scopus (1412) Google Scholar The recent Rome III consensus proposed to make a distinction between FD symptoms, and nausea and vomiting disorders, because the symptoms of nausea and vomiting have been associated with the presence of delayed gastric emptying in large patient cohorts.5Tack J. Talley N.J. Camilleri M. et al.Functional gastroduodenal disorders.Gastroenterology. 2006; 130: 1466-1479Abstract Full Text Full Text PDF PubMed Scopus (1412) Google Scholar However, only 34% of the NIDDK consortium patients fulfilled criteria for chronic idiopathic nausea.4Parkman H.P. Yates K. Hasler W.L. et al.National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research ConsortiumClinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.Gastroenterology. 2011; 140: 101-115Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar With the highest symptom ratings in the NIDDK cohort for the cardinal FD symptoms (feelings of stomach fullness, inability to finish a meal, and feeling excessively full after a meal), the current cohort confirms that this symptom pattern does not allow to predict delayed gastric emptying or vice versa.2Talley 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 Scholar An acute and presumed postinfectious origin, which was present in a large subset of the idiopathic gastroparesis patients, has also been reported in FD and is associated with a higher prevalence of nausea and vomiting.6Tack J. Demedts I. Dehondt G. et al.Clinical and pathophysiological characteristics of acute-onset functional dyspepsia.Gastroenterology. 2002; 122: 1738-1747Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar Among physicians as well as regulatory authorities, “gastroparesis” is often considered a diagnosis more relevant, more worthy of treatment, and more “serious” than FD. This is closely associated with the assumption that gastroparesis is caused by neuromuscular dysfunction in the upper GI tract, whereas in FD, like in other functional disorders, psychosocial factors and psychiatric comorbidity are likely to play a major pathophysiologic role.7Tack 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 However, in the current cohort, high levels of anxiety and depression were found, anxiety and depression were significantly associated with the symptom severity, and depression was among the factors that was independently associated with symptom severity as assessed by the gastroparesis cardinal symptom index.4Parkman H.P. Yates K. Hasler W.L. et al.National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research ConsortiumClinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.Gastroenterology. 2011; 140: 101-115Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar These findings are highly reminiscent of FD, where symptom severity is also determined by depression, as well as “somatization,” which was not assessed in the current cohort.8Van Oudenhove L. Vandenberghe J. Geeraerts B. et al.Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation?.Gut. 2008; 57: 1666-1673Crossref PubMed Scopus (151) Google Scholar Hence, idiopathic gastroparesis symptom severity is also majorly influenced by psychological comorbidities. Measuring gastric emptying in upper GI symptoms reminiscent of gastroparesis or FD might be relevant if it determined symptom severity or treatment outcomes. Increasing delays in the gastric emptying rate were associated with higher severity scores for nausea, vomiting, and loss of appetite. Similar findings have been reported in FD, and in FD with delayed emptying, and in these patients, better correlations were found between symptom severity and pattern and other aspects of gastric sensorimotor function such as hypersensitivity to gastric distention or impaired gastric accommodation.3Karamanolis G. Caenepeel P. Arts J. et al.Determinants of symptom pattern in idiopathic severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction?.Gut. 2007; 56: 29-36Crossref PubMed Scopus (103) Google Scholar, 7Tack 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 In the current cohort, and similar to previous observations,3Karamanolis G. Caenepeel P. Arts J. et al.Determinants of symptom pattern in idiopathic severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction?.Gut. 2007; 56: 29-36Crossref PubMed Scopus (103) Google Scholar the relation between overall symptom severity and delayed emptying was poor. In fact, gastric retention at 2 and 4 hours did not differ between mild, compensated gastroparesis and gastric failure patients, and when overall symptom severity was quantified based on the gastroparesis cardinal symptom index, gastric retention was a risk factor of marginal importance compared with the presence of depression and migraine headaches. Finally, there is a broad body of literature that has established that the presence and severity of delayed gastric emptying, and the improvement under therapy, do not predict symptomatic responsiveness to prokinetic therapy.9Tack J. Prokinetics and fundic relaxants in upper functional gastrointestinal disorders.Curr Opin Pharmacol. 2008; 8: 690-696Crossref PubMed Scopus (110) Google Scholar, 10Arts J. Caenepeel P. Verbeke K. et al.Influence of erythromycin on gastric emptying and meal related symptoms in functional dyspepsia with delayed gastric emptying.Gut. 2005; 54: 455-460Crossref PubMed Scopus (115) Google Scholar Based on symptom associations and treatment impact in the present and previous studies, it seems not more justified to distinguish idiopathic gastroparesis from FD as it would be to distinguish idiopathic impaired accommodation or idiopathic gastric hypersensitivity.7Tack 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 It seems that the existence of a separate nomenclature for idiopathic gastroparesis has more to do with the fact that delayed emptying was historically the first hypothesis to be addressed in unexplained upper GI symptoms, and with the widespread availability of gastric emptying testing, than with its relevance to clinical management. It is in the interest of clinicians dealing with patients with upper GI dysmotility-like symptoms, of regulatory agencies, and of the pharmaceutical industry developing prokinetic drugs to find a way forward from the ill-defined and artificial distinction between FD with delayed emptying and idiopathic gastroparesis. In the past, higher cutoffs for delayed emptying or confirmation of delayed emptying on ≥2 separate gastric emptying tests have been proposed as measures to identify idiopathic gastroparesis, but this has not been based on solid evidence.9Tack J. Prokinetics and fundic relaxants in upper functional gastrointestinal disorders.Curr Opin Pharmacol. 2008; 8: 690-696Crossref PubMed Scopus (110) Google Scholar, 10Arts J. Caenepeel P. Verbeke K. et al.Influence of erythromycin on gastric emptying and meal related symptoms in functional dyspepsia with delayed gastric emptying.Gut. 2005; 54: 455-460Crossref PubMed Scopus (115) Google Scholar Resolving the issue requires analysis of large patient samples, and the NIDDK cohort seems an ideal vehicle to do so. It remains conceivable that a subgroup of patients have characteristics or symptoms that are more clearly driven by delayed gastric emptying, and we speculate that the main candidate features could be the presence of weight loss or the need for nutritional support. Conversely, it is conceivable that elimination of patients based on certain features, for instance being overweight and potentially some psychosocial features, leads to identification of a subgroup that would justify the label “idiopathic gastroparesis.” Until then, “idiopathic gastroparesis” in our opinion equals “FD with delayed gastric emptying”: We believe that idiopathic gastroparesis should be considered at best a candidate mechanism contributing to unexplained upper GI symptoms (FD), rather than a separate “disease entity,” “disorder,” or “syndrome.” Moreover, based on empirical evidence, including the present NIDDK study, its importance as a mechanism may well be modest. ReplyGastroenterologyVol. 140Issue 7PreviewWe thank Drs Janssen, Van Oudenhove, Bisschops, and Tack for highlighting an important debate in the field, namely, the differences between idiopathic gastroparesis and functional dyspepsia. We would like to respond to several opinions that are discussed in their letter. Full-Text PDF" @default.
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• W2057000827 title "Idiopathic Gastroparesis or Functional Dyspepsia With Delayed Gastric Emptying: Where Is the Difference?" @default.
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