Eating sustains life. For some, preparing and eating food provides immense satisfaction. For others, eating causes significant distress. That eating can generate such a range of sensations highlights the fact that the stomach is an extraordinarily complex sensorimotor organ. Tirelessly, subconsciously, and usually without complaint, the stomach performs 3 key functions: accommodating ingested food; triturating gastric contents; and emptying liquids and small aliquots of ground food into the duodenum.
These functions generally occur without causing distress; however, a significant portion of the population suffers from meal-related symptoms. Typical symptoms that develop due to abnormalities in gastric sensorimotor function include epigastric pain, burning, pressure or fullness, nausea, vomiting, early satiation, bloating, and belching (1-3). Unfortunately, these symptoms are non-specific, and potentially represent any number of gastrointestinal organic, functional or motility disorders (1-5). For example, early satiation is a cardinal symptom of functional dyspepsia (FD), although it is also commonly reported by patients with gastroparesis (GP) (1-3). However, FD is much more common than gastroparesis with a prevalence of approximately 7%-10%, compared to modeling estimates which suggest that 0.01%-1.8% of the population have symptoms consistent with GP (6-10). Similarly, symptoms of nausea and vomiting are common in patients with GP; however, they are also present in cyclic vomiting syndrome (CVS), cannabinoid hyperemesis syndrome (CHS), and chronic nausea and vomiting syndrome (CNVS), with a combined estimated prevalence rate of 2% for the latter 3 disorders (11,12). These disorders cause a significant negative impact to the health care system and dramatically reduce patients’ quality of life (13-17). Unfortunately, the Food and Drug Administration-approved treatment options are limited only to metoclopramide for GP (18).
In the following sections, we provide a proposed diagnostic approach to the evaluation of gastric sensorimotor disorders based on current knowledge of the latest clinical and research diagnostic tool kit. This includes a brief overview of normal gastric function, a concise review of the most common gastric sensorimotor disorders, and tests of gastric motor and sensory function. A comprehensive review of treatment options is beyond the scope of this narrative review; however, a brief overview is provided in Supplemental Table 1 (see Supplemental Digital Content).
Normal gastric neuromuscular function
Anatomically, the stomach consists of 4 separate areas: the cardia, fundus, body, and antrum. Physiologically, the stomach functions as 2 distinct components. The proximal stomach (fundus and upper body) relaxes to accommodate ingested food volumes (i.e., receptive relaxation) and has little phasic activity. The distal stomach (antrum and lower body) generates strong muscular contractions to triturate and then expel ingested food (Figure 1). Normal gastric motor function involves a series of subconscious, highly complex, coordinated electromechanical events that depend upon normally functioning smooth muscle, an intact gastric pacemaker (formed by the interstitial cells of Cajal), and a variety of neurotransmitters (19). Gastric motor activity is generally divided into 2 states, fasting and fed.
In the fasting state (the interdigestive state), intraluminal manometric catheters and extra-luminal electrodes evaluating electromechanical activity of the stomach reveal the migrating motor complex (MMC), a cyclic motor pattern that lasts approximately 130 minutes (see Supplemental Figure 1, Supplementary Digital Content) (20,21). Phase 1 of the MMC is a period of quiescence that may last 50-70 minutes. Irregular antral contractions characterize Phase 2 (30-50 minutes), whereas Phase 3 is characterized by strong, rhythmic antral contractions that occur at a rate of 2-3 per minute (the rate of the gastric pacemaker potential), and which last 3-5 minutes on average. Phase 3 contractions usually begin in the antrum and then migrate through the pylorus into the duodenum. However, they can also originate from the duodenum. Phase 3 functions to clear material from the stomach and small intestine, and also functions as a hunger signal (22). Absence of Phase 3 activity has been associated with bacterial overgrowth, GP, loss of appetite and intestinal pseudo-obstruction (8, 23).
The fed response develops after ingesting a meal. The MMC, if present, stops, and sporadic irregular contractions develop in the lower body and antrum of the stomach. The fed response may last for several hours depending upon the size and content of the meal. Normal antroduodenal coordination ensures that antral peristalsis is coordinated with decreased pyloric and duodenal resistance to ensure efficient emptying with each antral contraction. A return to the fasting state occurs after food is emptied from the stomach.
Disorders of gastric motor and sensory function
The accurate diagnosis of gastric motor and sensory disorders can be difficult based on symptoms alone, as most are nonspecific and can occur either alone or in combination. Diagnostic testing is often pursued, although symptoms are not always concordant with test results (see diagnostic test section below). A list of the most common gastric sensorimotor disorders is found in Table 1. As the evaluation begins, conditions that may mimic or coincide with common gastric motor and sensory disorders need to be considered. For example, vascular disorders of the upper gastrointestinal tract, such as celiac artery compression syndrome and superior mesenteric artery syndrome, can cause symptoms of postprandial pain, nausea and vomiting (see Table 2). A history of jaundice or a prior episode of pancreatitis can help identify an underlying hepatobiliary cause. A history of severe headaches, visual changes or dizziness may point to a central or peripheral (autonomic) nervous system cause or an inner ear disorder. Medications, both prescribed and over-the-counter, should be carefully reviewed, as several classes are associated with adverse gastrointestinal symptoms. Warning signs should be addressed (unintentional weight loss, history of anemia, family history of malignancy) and managed appropriately, especially in the elderly. Patients should be questioned about food-related symptoms to help tease out the impact of eating, and also to determine whether a primary or secondary eating disorder is present (24). A complete review of each of these disorders is beyond the scope of this review; however, the diagnostic evaluation can be streamlined by using a series of key questions (Figure 2).
Is belching and burping the predominant symptom?
Belching is categorized as supragastric or gastric (1). The mechansims behind supragastric belching are air suction or air injection, and learned abnormal behaviors in response to unpleasant feelings in the abdomen. Gastric belching is characterized by air venting from the stomach via transient relaxation of the lower esophageal sphincter.
Is the patient truly vomiting?
Persistent or recurrent regurgitation of recently ingested food into the mouth with subsequent spitting or remastication and swallowing, and without preceding retching, is diagnostic of rumination syndrome. Although the pathophysiology of rumination syndrome is not understood completely, episodes are thought to involve increased intra-abdominal pressure generated by voluntary but unintentional contractions of the abdominal muscles, coupled with negative intrathoracic pressure which allows for permissive retrograde flow of gastric contents (25).
Has the patient undergone prior esophageal or gastric surgery?
Prior fundoplication, bariatric surgery, cholecystectomy, or esophageal or gastric resection increases the likelihood of dumping syndrome or post-surgical GP. Early dumping syndrome is characterized by abdominal pain, bloating, borborygmi, nausea, diarrhea, and vasomotor symptoms (e.g. fatigue, desire to lie down after meals, flushing, palpitations, diaphoresis, tachycardia, hypotension and, rarely, syncope), while late dumping syndrome is characterized by (reactive) hypoglycemia (26,27).
Are symptoms intermittent and/or cyclical?
Most patients with GP, dumping syndrome, chronic nausea and vomiting syndrome (CNVS), and dyspepsia have persistent, rather than intermittent, symptoms. Episodic nausea and vomiting, lasting less than 1 week in duration and separated by at least 1 week in time, is most consistent with cyclical vomiting syndrome (CVS). A hallmark feature of CVS is the absence of vomiting between episodes (1). A personal or family history of migraine headaches is supportive of the diagnosis, as these 2 disorders share similar clinical features, perhaps mediated by autonomic dysfunction.
Is the patient using cannabis?
Widely available for both recreational and medicinal usage, cannabis has become a more frequently encountered etiology for stereotypical episodic vomiting, resembling CVS but known as cannabinoid hyperemesis syndrome (CHS), that develops after its prolonged and daily use. In the appropriate setting, relief with vomiting and with prolonged hot baths or by sustained cessation of use, is nearly pathognomonic of CHS (1).
Is vomiting a predominant symptom?
If so, gastroparesis or chronic nausea and vomiting syndrome are the more likely diagnoses. A gastric emptying test should be delayed in patients with GP (28-30) and normal in patients with chronic nausea and vomiting syndrome (CNVS), which is defined by bothersome nausea, occurring ≥ 1 day per week, and/or ≥ 1 vomiting episode per week, without evidence of a causative organic disease (1). Eating disorders and rumination must be excluded. CNVS can be distinguished from CVS as symptoms are more persistent, as opposed to the episodic nature of CVS. Prolonged cannabis can contribute to and exacerbate symptoms of both CNVS and CVS, and ideally should be stopped for a minimum of 60 days while monitoring symptoms. Combined estimated prevalence rate of CVS, CHS and CNVS is 2% (11,12). When vomiting is not the predominant symptom, but the clinical picture is dominated by 1 or more of the defining symptoms of FD, namely postprandial fullness, early satiation, epigastric pain and/or epigastric burning, then FD is a more likely cause. The prevalence of FD is approximately 7%-10% (6-10). This can be further divided into postprandial distress syndrome (PDS), characterized by meal-induced dyspeptic symptoms (postprandial fullness and/or early satiation); epigastric pain syndrome (EPS), characterized by pain or epigastric burning; or overlapping PDS and EPS, as defined in the Rome IV criteria (1, 31,32). Upper endoscopy (EGD) is required to rule out an organic disorder as the cause of symptoms, although the majority of patients with dyspeptic symptoms and without warning signs on history or physical examination will have a normal EGD (1-3). Therefore, in clinical practice, a young person with a classic clinical history suggestive of FD with normal routine lab tests and without warning signs, often receives a diagnosis of and is treated empirically for FD without undergoing endoscopy.
Tests of gastric sensorimotor function
Clinicians and researchers have evaluated a variety of techniques to objectively measure gastric motor function and gastric emptying (GE; Figure 3). These tests are important because symptoms do not always accurately reflect underlying pathophysiology (4,12, 33). For example, it is now acknowledged that gastroparesis and functional dyspepsia are overlapping disorders, and although still somewhat controversial, symptoms do not always correlate with gastric emptying rates (34,35). The prevalence of FD is approximately 7%-10%, while prevalence data and modeling estimates suggest that 0.01%-1.8% of the population have symptoms consistent with GP (6-10). Tests to distinguish between the two vary in terms of level of invasiveness, tolerability, reliability, accuracy, safety, and cost. A diagnostic algorithm is provided in Figure 4 (A-C).
Ultrasonography (US) is simple, safe, inexpensive, and noninvasive (36). Antral contractions (frequency and amplitude), antral area, transpyloric flow, and gastric residual rates can be measured after liquid meal ingestion (37). Limitations include reduced reliability in obese subjects and when air is present in the GI tract (Table 3). The test is operator dependent and results are more reliable with liquid, rather than solid, meals (38). Controlled trials directly comparing US to gastric scintigraphy, using standardized meals, in patients with GP or FD are not available. For these reasons, US cannot be recommended to measure gastric motor function in clinical practice.
Gastric emptying scintigraphy
Gastric scintigraphy (GES) is considered the gold standard for measuring gastric emptying, although breath tests (described below) are being increasingly used. Scintigraphy is noninvasive, does not disturb normal physiology, and is easily quantified. As the test meal contains a small amount of radiation (99Tc) it should not be used in pregnant or lactating women or children. Guidelines on correctly performing GES were published nearly 20 years ago (28), although most centers fail to follow key protocol requirements (29). GES does require intact anatomy and should be interpreted with caution in the setting of bariatric or gastric surgery. Scintigraphy can distinguish rapid, normal, and delayed emptying in patients with chronic nausea and vomiting (11,30). In a study of 225 consecutive patients evaluated with using a standardized solid meal, delayed gastric emptying was detected with greater sensitivity at 4 hours compared to 2 hours, and the positive predictive value increased as well (39). Hence, including a 4-hour scan, and not terminating the investigation after a 2-hour scan, is essential to make a correct diagnosis of GP. It is important to recognize that 20%-30% of patients with FD will have a mild delay in gastric emptying; however, this is distinct from the moderate-severe delays in gastric emptying characteristic of gastroparesis (31,32).
Breath tests are noninvasive, easily repeatable, do not expose patients to radiation, or require expensive equipment, operator or interpretive expertise (40). Different isotopes are used to label liquids (13C-acetate) and solids (13C-octanoic acid or 13C-Spirulina platensis; (41,42). After emptying from the stomach, the isotope is absorbed in the small intestine, metabolized to 13CO2, and expelled during expiration. Results can be adversely influenced by metabolic abnormalities (e.g., malabsorption, pancreatic or pulmonary insufficiency, hepatitis). The 13C-spirulina breath test was approved by the US Food and Drug Administration (FDA) in 2015 (43). In a prospective study involving both healthy controls and patients with FD, the concordance correlation coefficient between scintigraphic and breath test gastric emptying t ½ times was quite high at 0.95 for all subjects, 0.83 for healthy subjects, and 0.94 for FD patients (44). Breath tests are an acceptable alternative to GES when objective measures of gastric emptying are required.
Wireless motility capsule
The wireless motility capsule (WMC; SmartPill; Given Imaging, Yoqneam, Israel) measures temperature, pressure, and pH. The capsule was FDA approved to measure GE in 2006. It is swallowed with a standardized meal and water after an overnight fast. An abrupt rise in pH of > 2 units above gastric pH baseline indicates exit from the stomach into the duodenum. Gastric residence time of the WMC correlates well with gastric retention of a standard scintigraphic meal (45). Overall agreement for WMC and gastric scintigraphy was 75.7% in a prospective, multicenter study of 167 patients (kappa = 0.42) (46). In a prospective study of 72 patients with diabetes and symptoms of GP, the sensitivity and specificity for making the diagnosis of GP using a standard cutoff value of 300 minutes for delayed gastric emptying was 0.92 and 0.73, respectively (47). A simultaneous WMC and antroduodenal manometry comparison study found that the WMC emptied primarily with return of Phase III of the MMC, making it an indirect measure of gastric emptying (48). The WMC is a reasonable alternative to gastric scintigraphy and breath tests for the evaluation of gastric emptying, with the understanding that the WMC primarily assesses the rate of clearance of indigestible material from the stomach (the capsule as opposed to food).
Antroduodenal manometry (ADM) is invasive but safe, although only available at a limited number of academic centers. Patients are typically studied in a fasting state, after medication challenges (e.g., erythromycin and/or octreotide), and after a meal challenge (49). ADM can identify and distinguish major myopathic and neuropathic disorders that affect GE (e.g., absence of Phase III of the MMC, severe antral hypomotility, absence of response to erythromycin challenge; see supplemental Figure 1, Supplemental Digital Content). In small studies of patients with GP, pylorospasm was identified in some, and this was thought to contribute to symptom generation (50). Due to limited availability, these findings have not been confirmed in larger trials; however, Endoscopic functional luminal imaging probe (EndoFLIP) may provide confirmatory data. Although large trials evaluating the utility of ADM in patients with GP of all subtypes have not been performed, one study demonstrated a significant correlation between reduction in postprandial antral contractility and delayed gastric emptying of solids (51). In summary, this test should be reserved for patients with unexplained, persistent ongoing symptoms who have failed standard therapy.
The gastric barostat is considered the gold standard to evaluate gastric accommodation (GA). The barostat consists of an oversized, flaccid bag connected to a pressure transducer and air pump via a double-lumen catheter. The barostat can be used to measure GA since a constant pressure can be maintained within the bag by injecting or withdrawing air through the catheter. Gastric volumes are measured indirectly as intraballoon pressures fluctuate with changes in gastric tone. The test is reproducible and has demonstrated that abnormal GA is common in patients with FD (52,53). The test does not measure gastric emptying. Disadvantages to the test include being invasive, uncomfortable, and limited to only a few specialized centers worldwide. This test should be limited to research studies and specialized motility centers.
Single Photon Emission CT.
Single photon emission computer tomography (SPECT)_ has been shown to be comparable to the gastric barostat at assessing changes in gastric volume in both the fasting and fed state (54). SPECT is a safe, non-invasive test that does not perturb normal physiology. After intravenous injection with 99mTc-pertechnate, which is taken up by gastric mucosal cells, 3 dimensional images of the stomach are reconstructed to provide a measure of gastric volume in both the fasting and fed state. SPECT can provide valuable information on GA, but, like the barostat, is not a reliable measure of GE (55,56). At present, this test is currently limited to research studies, although this could be considered clinically in select patients with severe dyspeptic symptoms who fail standard therapy.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) to evaluate gastric motility was first reported in 1992 (57). MRI is safe, non-invasive, can be performed for prolonged periods of time, and can be used to assess gastric response to medications. In contrast to SPECT, MRI can distinguish meal contents from air. Gastric contractions, GA, and GE can all be measured by MRI--the latter correlating well with scintigraphy (58). MRI appears comparable to SPECT at measuring GA, although estimated gastric volumes may be slightly lower (59). Disadvantages include cost, limited availability, significant time spent analyzing images, and the requirement that imaging be performed in the supine position, which is not physiologic. At present, this is primarily used in the research setting, but also could be considered in select patients with severe dyspeptic symptoms who fail standard therapy in the near future.
Intragastric pressure monitoring
Studies using high resolution manometry of the stomach showed that nutrient ingestion induces an initial drop in intra-gastric pressure (IGP) of 5-6 mm Hg on average, followed by gradual recovery (60). This method underwent some validation as a measure of gastric accommodation, by showing its dependence on nitric oxide synthase and its link with meal-induced satiation during liquid nutrient drink challenge, identifying the rise in intra-gastric pressure from nadir as a determinant of meal-induced satiation (60). A combined IGP-nutrient-infusion scintigraphy study confirmed that impaired intragastric distribution of nutrient (less accumulation in the fundus, more in the antrum), a marker for impaired accommodation, is associated with suppressed drop in IGP upon nutrient infusion and earlier satiation (61). This technique is currently only used in research settings.
EndoFLIP uses impedance planimetry to record cross sectional area and minimum diameter of any hollow structure. Pressure/volume curves can be generated, leading to an estimate of sphincter distensibility and compliance. EndoFLIP has primarily been used to study the esophagus although limited data is available on the pylorus, with some studies showing diminished pyloric distensibility in select patients with gastroparesis (62). The role of EndoFLIP in the diagnosis of gastric motor disorders is considered experimental at present.
Radio-opaque markers to measure GE are of historical interest only as they have limited utility in the evaluation of gastric motor activity and are not recommended for clinical or research purposes. In general, larger markers empty more slowly than smaller markers, markers taken with liquid empty faster than markers ingested with food, and larger markers appear to empty in association with Phase III of the MMC (48,63,64).
Cutaneous electrogastrography (EGG) measures gastric myoelectric activity (frequency and amplitude). Patients are typically measured fasting and after a standard meal. The normal frequency is 2-4 cpm (65). EGG does not measure GE or GA, and does not diagnose any specific disorder. Although safe and non-invasive, the clinical utility of this test is unclear, and we do not recommend its routine use in the clinical setting.
Not all reported symptoms represent gastric motor dysfunction. Many symptoms likely represent gastric sensory dysfunction. Although data is quite limited, a centrally mediated process (e.g., a conditioned response, up-regulated descending pathways) could also play a role. Drink tests were developed as a noninvasive alternative to the barostat. They attempt to measure GA and assess patient-reported unbearable fullness described as maximum tolerated volume (MTV) as a surrogate symptom for hypersensitivity (see Table 4). Drink tests are easy to perform and are predicated on the assumption that GA, gastric sensation, and to some extent GE, influence maximum volume ingestion and symptom generation in patients with disorders of gastric sensation (66,67). Drink tests are performed using either water or caloric-containing solutions with variable percentages of macronutrients (i.e. Ensure, Nutridrink, and Boost) at various ingestion rates (see supplemental Figure 2, Supplemental Digital Content). The reported MTV is documented along with reported symptoms at a set time (usually 5 minutes) using a visual analogue scale (VAS) ranging from “unnoticeable” to “unbearable” with anchors for bloating, fullness, nausea and pain (68). As dyspeptic symptoms can persist even while fasting and do not always correlate with gastric volume capacity, drink tests are not ready for clinical use. However, individual and aggregate post-ingestion symptom scores are more likely to be higher in patients with FD than controls, which highlights the complex interplay of intestinal distention, neurohumoral signals and psychological factors in disorders of gastric sensation (69). Therefore, drink tests are thought to have a place in patient-reported clinical research (70).
Symptom-based questionnaires are another patient-reported measure used to quantify and categorize disordered gastric sensation, although currently they are unable to accurately distinguish between sensory and motor disorders and do not necessarily predict abnormal physiologic testing. While symptoms of postprandial fullness and early satiation have been shown to correlate with severity of gastroparesis on the 20-item Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM) (71), other symptom-based patient reported outcomes in FD and related disorders have poor concordance with physiologic gastrointestinal dysfunction (72). Validated instruments, including the Gastroparesis Cardinal Symptom Index (GCSI) (73) and the Nepean Dyspepsia Index (NDI) (74), used to guide clinical trials with goals of improving accuracy of diagnosis, assessing treatment responses, identifying coexistent psychological comorbidity, and correlating symptoms with physiologic testing have yet to demonstrate clinical reliability consistently (5). For clinical purposes, until more sensitive questionnaires are developed, it is recommended that clinicians screen for weight loss, ask patients to keep a daily diary for 2 weeks documenting abdominal pain using a numerical rating scale 0-10 (none to worst pain imaginable), perform upper endoscopy with luminal evaluation if indicated, and consider assessments of accommodation (e.g. SPECT) and/or transit (e.g. scintigraphy) with the goal of identifying a unifying diagnosis.
Gastric sensorimotor conditions are highly prevalent disorders that significantly affect patients’ quality of life and negatively impact the health care system. A series of clinically focused questions can be used to help identify and distinguish these chronic disorders (Figure 2). Although not the focus of this review, empiric therapy can be initiated for many of these disorders (e.g., rumination syndrome, FD) based on symptoms, a normal physical examination, and the absence of warning signs (2, 3). When necessary, diagnostic testing should be performed in a logical, step-wise manner, with the underlying premise that test results should guide therapeutic management (Figure 4). Accurately measuring gastric emptying helps distinguish gastroparesis from other disorders (FD, CNVS, CVS, CHS) which may help to guide appropriate therapy.
CONFLICTS OF INTEREST
Guarantor of article: Brian E. Lacy, Ph.D., M.D., FACG.
Specific author contributions: Design, research, writing, and editing of this manuscript B.E.L., M.D.C., D.J.C., T.N.L., M.S., J.T.
Financial Support: None to report.
Potential competing interests: None to report.
1. Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal disorders. Gastroenterology 2016; 150:1380–92.
2. Ford AC, Mahadeva S, Carbone MF, et al. Functional dyspepsia. Lancet 2020; 396 (10263):1689-702.
3. Moayyedi PM, Lacy BE, Andrews CN, et al. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol 2017; 112:988-1013.
4. Vanheel H, Carbone F, Valvekens L, et al. Pathophysiological abnormalities in functional dyspepsia: subgroups according to the Rome III criteria. Am J Gastroenterol 2017; 112: 132-40.
5. Lacy BE, Everhart K, Crowell MD. Functional dyspepsia: clinical symptoms, psychological findings, and GCSI scores. Dig Dis Sci 2019; 64: 1281-7.
6. Ford AC, Marwaha A, Sood R, Moayyedi P. Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis. Gut 2015; 64:1049-57.
7. Jung HK, Choung RS, Locke GR, et al. The incidence, prevalence and outcomes of patients with gastroparesis in Olmsted County, Minnesota from 1996 to 2006. Gastroenterology 2009; 136: 1225–33.
8. Rey E, Choung RS, Schleck CD, Zinsmeister, et al. Prevalence of hidden gastroparesis in the community: the gastroparesis "iceberg". J Neurogastroenterol Motil 2012;18:34-42.
9. Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation global study. Gastroenterology 2021; 160:99-114.
10. Ye Y, Jiang B, Manne S, et al. Epidemiology and outcomes of gastroparesis, as documented in general practice records, in the United Kingdom. Gut 2021; 70: 644-53.
11. Lacy BE, Parkman HP, Camilleri M. Chronic nausea and vomiting: evaluation and treatment. Am J Gastroenterol 2018; 113:647-59.
12. Aziz I, Palsson OS, Whitehead WE, et al. Epidemiology, clinical characteristics, and associations for Rome IV functional nausea and vomiting disorders in adults. Clin Gastroenterol Hepatol 2019; 17: 878-86.
13. Peery AF, Crockett SD, Murphy CC, et al. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018. Gastroenterology 2019; 156:254-72.
14. El-Serag HB, Talley NJ. Health-related quality of life in functional dyspepsia. Aliment Pharmacol Ther 2003; 18:387-93.
15. Brook RA, Kleinman NL, Chound RS, et al. Functional dyspepsia impacts absenteeism and direct and indirect costs. Clin Gastroenterol Hepatol 2010; 8:498-503.
16. Lacy BE, Weiser KT, Kennedy AT, et al. Functional dyspepsia: the economic impact to patients. Aliment Pharmacol Ther 2013;38:170-7.
17. Lacy BE, Crowell MD, Mathis C, et al. Gastroparesis: quality of life and health care utilization. J Clin Gastroenterol 2018; 52: 20-4.
18. US Food and Drug Administration. Highlights of prescribing information (Reference ID: 4145755). August 2017. Accessed November 23, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017854s062lbl.pdf
19. Goyal RK, Guo Y, Mashimo H. Advances in the physiology of gastric emptying. Neurogastroenterol Motil 2019; 31:e13546.
20. Dooley CP, DiLorenzo C, Valenzuela JE. Variability of migrating motor complex in humans. Dig Dis Sci 1992; 37: 723-8.
21. Deloose E, Janssen P, Depoortere I, Tack J. The migrating motor complex: control mechanisms and its role in health and disease. Nat Rev Gastroenterol Hepatol 2012; 9:271-85.
22. Tack J, Deloose E, Ang D, et al. Motilin-induced gastric contractions signal hunger in man. Gut 2016; 65:214-24.
23. Vantrappen G, Janssens J, Hellemans J, Ghoos Y. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest 1977; 59:1158-66.
24. Werlang ME, Sim LA, Lebow JR, Lacy BE. Assessing for eating disorders: a primer for gastroenterologists. Am J Gastroenterol 2021; 116:68-76.
25. Halland M, Pandolfino J, Barba E. Diagnosis and Treatment of Rumination Syndrome. Clin Gastroenterol Hepatol 2018;16:1549-55.
26. van Beek AP, Emous M, Laville M, Tack J. Dumping syndrome after esophageal gastric or bariatric surgery: pathophysiology, diagnosis and management. Obesity Reviews 2017; 18:68-85.
27. Scarpellini E, Arts J, Karamanolis G, et al. International consensus on the diagnosis and management of dumping syndrome. Nat Rev Endocrinol 2020;16:448-66.
28. Tougas G, Eaker EY, Abell TL, et al. Assessment of gastric emptying using a low-fat meal: establishment of international control values. Am J Gastroenterol. 2000; 95:1456-62.
29. Wise J, Vazquez-Roque M, Crowell MD, Lacy BE. Gastric Scintigraphy: lack of adherence to national guidelines. Dig Dis Sci 2020;66:2897-906.
30. Camilleri M, Parkman HP, Shafi MA, et al. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108:18-37.
31. Talley NJ, Locke GR, Saito YA, et al. Effect of amitriptyline and escitalopram on functional dyspepsia: a multicenter, randomized controlled study. Gastroenterology 2015; 149:340-9.
32. Carbone F, Buysscher RD, Van den Houte K, et al. Relationship between gastric emptying rate and simultaneously assessed symptoms in functional dyspepsia. Clin Gastroenterol Hepatol 2021; https://doi.org/10.1016/j.cgh.2021.03.023
33. Vanheel H, Carbone F, Valvekens L, et al. Pathophysiological abnormalities in functional dyspepsia subgroups according to the Rome III criteria. Am J Gastroenterol 2017; 112:132-40.
34. Pasricha JP, Grover M, Yates KP, et al. Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features. Gastroenterology 2021; 160:2006-17.
35. Vijayvargiya P, Jameie-Oskooei S, Camilleri M, et al. Association between delayed gastric emptying and upper gastrointestinal symptoms: a systematic review and meta-analysis. Gut 2019; 68:804-13.
36. Bateman DN, Whittingham TA. Measurement of gastric emptying by real-time ultrasound. Gut 1982; 23:524-7.
37. Bolondi L, Bortolotti M, Santi V, et al. Measurement of gastric emptying by real-time ultrasonography. Gastroenterology 1985; 89:752-9.
38. Marzio L, Giacobbe A, Conoscitore P, et al. Evaluation of the use of ultrasonography in the study of liquid gastric emptying. Am J Gastroenterol 1989; 84:496-500.
39. Ziessman HA, Bonta DV, Goetze S, Ravich WJ. Experience with a simplified, standardized 4-hour gastric-emptying protocol. J Nuc Med 2007; 48: 568-72.
40. Ghoos YF, Maes BD, Geypens BJ, et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. Gastroenterology 1993; 104:1640-7.
41. Lee JS, Camilleri M, Zinsmeister AR, et al. A valid, accurate, office based non-radioactive test for gastric emptying of solids. Gut 2000; 46:768-73.
42. Chey WD, Shapiro B, Zawadski A, et al. Gastric emptying characteristics of a novel (13)C-octanoate-labeled muffin meal. J Clin Gastroenterol 2001; 32: 394-9.
43. US Food and Drug Administration. Summary of safety and effectiveness data (SSED). PMA Number P110015. April 6, 2015. Accessed February 18, 2021. https://www.accessdata.fda.gov/cdrh_docs/pdf11/P110015b.pdf
44. Bharucha AE, Camilleri M, Veil E, et al. Comprehensive assessment of gastric emptying with a stable isotope breath test. Neurogastroenterol Motil 2013; 25:e60-9.
45. Maqbool S, Parkman HP, Friedenberg FK. Wireless capsule motility: comparison of the SmartPill GI monitoring system with scintigraphy for measuring whole gut transit. Dig Dis Sci 2009; 54:2167-74.
46. Lee AA, Rao S, Nguyen LA, et al. Validation of diagnostic and performance characteristics of the wireless motility capsule in patients with suspected gastroparesis. Clin Gastroenterol Hepatol 2019; 17:1770-9.
47. Sangnes DA, Softeland E, Bekkelund M, et al. Wireless motility capsule compared with scintigraphy in the assessment of diabetic gastroparesis. Neurogastroenterol Motil 2020; 32:e13771.
48. Cassilly D, Kantor S, Knight LC, et al. Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy. Neurogastroenterol Motil 2008; 20: 311-9.
49. Patcharatrakul T, Gonlachanvit S. Technique of functional and motility test: how to perform antroduodenal manometry. J Neurogastroenterol Motil 2013; 19: 395-404.
50. Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology 1986; 90: 1919-25.
51. Burton DD, Kim HJ, Camilleri M, et al. Relationship between impaired gastric emptying and abnormal gastrointestinal motility. Gastroenterology 1986; 91:94-9.
52. Sarnelli G, Vos R, Cuomo R, et al. Reproducibility of gastric barostat studies in healthy controls and in dyspeptic patients. Am J Gastroenterol 2001; 96:1047-13.
53. Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 1998; 115:1346-52.
54. Bouras EP, Delgado-Aros S, Camilleri M, et al. SPECT imaging of the stomach: comparison with barostat, and effects of sex, age, body mass index, and fundoplication. Gut 2002; 51:781-6.
55. Park SY, Acosta A, Camilleri M, et al. Gastric motor dysfunction in patients with functional gastroduodenal symptoms. Am J Gastroenterol 2017; 112:1689-99.
56. Chedid V, Halawi H, Brandler J, et al. Gastric accommodation measurements by single photon emission computed tomography and two-dimensional scintigraphy in diabetic patients with upper gastrointestinal symptoms. Neurogastroenterol Motil 2019; 31:e13581.
57. Schwizer W, Maecke H, Fried M. Measurement of gastric emptying by magnetic resonance imaging in humans. Gastroenterology 1992; 103:369-76.
58. Feinle C, Kunz P, Boesiger P, et al. Scintigraphic validation of a magnetic resonance imaging method to study gastric emptying of a solid meal in humans. Gut 1999; 44:106-11.
59. Fidler J, Bharucha AE, Camilleri M, et al. Application of magnetic resonance imaging to measure fasting and postprandial volumes in humans. Neurogastroenterol Motil 2009; 21:42-51.
60. Janssen P, Verschueren S, Giao Ly H, et al. Intragastric pressure during food intake: a physiological and minimally invasive method to assess gastric accommodation. Neurogastroenterol Motil 2011; 23:316-22.
61. Carbone F, Goelen N, Porters K, et al. Impaired gastric distribution of a meal is associated with impaired intragastric pressure measurement and satiation in FD [Abstract]. Gastroenterology 2017; 152:S304.
62. Desprez C, Roman S, Leroi AM, Gourcerol. The use of impedance planimetry (endoscopic functional lumen imaging probe, EndoFLIP) in the gastrointestinal tract: a systematic review. Neurogastroenterol Motil 2020; 32:313980.
63. Feldman M, Smith HJ, Simon TR. Gastric emptying of solid radiopaque markers: studies in healthy subjects and diabetic patients. Gastroenterology 1984; 87:895-902.
64. Smith HJ, Feldman M. Influence of food and marker length on gastric emptying of indigestible radiopaque markers in healthy humans. Gastroenterology 1986; 91:1452-55.
65. Yin J, Chen JDG. Electrogastrography: methodology, validation and applications. J Neurogastroenterol Motil 2013; 19: 5-17.
66. Park MI. How to interpret nutrition drink test. J Neurogastroenterol Motil. 2011;17:88-90.
67. Iida A, Kaneko H, Konagaya T, et al. How to interpret a functional or motility test - slow nutrient drinking test. J Neurogastroenterol Motil 2012;18:332-5.
68. Jones MP. Satiety testing: ready for the clinic? World J Gastroenterol 2008;14:5371-6.
69. Boeckxstaens GE, Hirsch DP, van den Elzen BD, et al. Impaired drinking capacity in patients with functional dyspepsia: relationship with proximal stomach function. Gastroenterology 2001;121:1054-63.
70. Tack J, Caenepeel P, Piessevaux H, et al. Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia. Gut 2003;52:1271-7.
71. Parkman HP, Hallinan EK, Hasler WL, et al. Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing. Neurogastroenterol Motil 2017;29.
72. Taylor F, Reasner DS, Carson RT, et al. Development of a symptom-based patient-reported outcome instrument for functional dyspepsia: a preliminary conceptual model and an evaluation of the adequacy of existing instruments. Patient 2016;9:409-418.
73. Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther 2003;18:141-50.
74. Talley NJ, Verlinden M, Jones M. Validity of a new quality of life scale for functional dyspepsia: a United States multicenter trial of the Nepean Dyspepsia Index. Am J Gastroenterol. 1999;94:2390–7.