Gastrointestinal Function: Selected Tests
Number: 0396
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses selected tests for gastrointestinal function.
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Medical Necessity
Aetna considers the following gastrointestinal function tests as medically necessary:
- Use of colonic motility studies (colonic manometry) to guide decision-making for surgery in children with refractory colonic motility / defecatory disorders;
- Radionuclide gastric emptying study for the evaluation of gastrointestinal motility disorders, and gastroparesis;
- Magnetic resonance enterography to evaluate and monitor Crohn's disease and other small bowel disorders.
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Experimental, Investigational, or Unproven
The following gastrointestinal function tests are considered experimental, investigational, or unproven because the effectiveness, or clinical utility of these approaches has not been established:
- 3D high-resolution manometry for quantification of esophago-gastric junction contractility;
- Body surface gastric mapping (Gastric Alimetry) for evaluations of gastric motility/gastroduodenal disorders and all other indications;
- Electrogastrography;
- Gastric emptying breath test (GEBT) for gastroparesis and for all other indications;
- High resolution esophageal pressure topography (HREPT);
- Immunoglobulin G (IgG) antibody blood test to identify food triggers associated with irritable bowel syndrome (e.g., Biomerica inFoods IBS);
- Malabsorption Evaluation Panel (Mayo Clinic Laboratories) (quantitative evaluation of alpha-1 antitrypsin, calprotectin, pancreatic elastase, and reducing substances) for the evaluation of intestinal dysbiosis, irritable bowel syndrome, malabsorption or small intestinal overgrowth of bacteria, and all other indications;
- PillSense System for the detection of upper gastrointestinal bleeding;
- Wireless capsule for measuring gastric emptying parameters (SmartPill GI Monitoring System) for the evaluation of gastric disorders (e.g., gastroparesis), intestinal motility disorders (e.g., chronic constipation), and all other indications because of inadequate published evidence of its diagnostic performance and clinical utility over conventional means of measuring gastric emptying.
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Related Policies
Background
There are several tests that have been trialed for the evaluation and diagnosis of transit and motility disorders of the gastrointestinal (GI) tract. The gold standard and most commonly performed test to evaluate gastric emptying is gastric scintigraphy, a radionuclide gastric emptying study used for the evaluation of gastrointestinal motility disorders, and gastroparesis. Colonic motility studies (colonic manometry) can help guide decision-making for surgery in children with refractory colonic motility / defecatory disorders. Magnetic resonance enterography is used to evaluate and monitor Crohn's disease and other small bowel disorders. However, there are alternative methods, such as electrogastrography, wireless motility capsule (WMC), high resolution esophageal pressure topography (HREPT), and 3D high-resolution manometry, that have been also been considered for use in the evaluation and diagnosis of GI function.
Colonic motility studies are used to assess the flow of intraluminal contents, the motions of the colonic wall that induce flow, and the control systems that integrate and regulate these processes. The approaches employed have consisted of manometric techniques to record colonic contractions, barostatic methods to measure colonic tone, and recordings of myoelectric signals from the colon that initiate and control muscular contractions. However, the study of colonic motility in a clinical setting proves to be difficult. Accurate positioning of the probes via colonoscopy requires pre-procedure cleansing of the colon, which raises the possibility of altered physiology. Recording of intra-luminal pressure, by means of manometric catheters inserted per rectum, requires prior bowel cleansing, which may modify colonic motility. In contrast to other segments of the gastro-intestinal tract, contents move through the colon in hours or days, instead of seconds to minutes; thus, prolonged observations are needed. Moreover, in contrast to the upper gastro-intestinal tract, in which reliable manometric recordings can be obtained, the larger diameter of the colon hinders the accurate detection of manometric events. Furthermore, interpretation of intra-luminal pressure measurements is complicated, because many contractions of the colonic wall do not occlude the lumen and therefore are detectable by manometry only if they cause significant pressure changes. And finally, all of these techniques, which continue to be used extensively in a research context, have not yet been standardized for routine clinical use.
Ghoshal et al (2007) stated that constipation is a common problem, which may be due to slow transit or fecal evacuation disorders. Though the screening test of colonic transit study using radio-opaque markers given at 0, 24 and 48 hours followed by abdominal X-ray at 72 hours is a good protocol in the West, it is not suitable for Indians who have a rapid gut transit. Nine patients with adult Hirschsprung disease, 11 with chronic intestinal pseudo-obstruction diagnosed using standard investigations and 11 healthy subjects were evaluated by colonic transit study using radio-opaque markers (SGmark), 20 each at O, 12 and 24 hours followed by an abdominal X-ray at 36 and 60 hours. The cut-off was determined by using receiver operating characteristic (ROC) curves, and sensitivity, specificity, positive and negative predictive values and diagnostic accuracy were determined. The total number of markers retained in the abdomen and those in the right segment at 36 hours in patients with Hirschsprung disease and chronic intestinal pseudo-obstruction was higher than that in healthy subjects though the number in the left and rectosigmoid segments were comparable. The abdominal X-ray at 60 hours, total number of markers and number in all segments were higher in patients with Hirschsprung disease and chronic intestinal pseudo-obstruction than in healthy subjects. The best cut-off by ROC curves at 36 and 60 hours was 30 and 14 markers, respectively. The sensitivity, specificity, positive and negative predictive values, diagnostic accuracy and area under the ROC curve at 36 hours were 90%, 82%, 90%, 82%, 87% and 0.9, respectively; the corresponding values at 60 hours were 95%, 100%, 100%, 92%, 97% and 0.99, respectively. The authors concluded that using the proposed protocol, the colonic transit study is able to distinguish patients with specific motility disorders causing constipation such as Hirschsprung disease and chronic intestinal pseudo-obstruction from healthy subjects with reasonable sensitivity and specificity, and shows that an abdominal X-ray at 60 hours is better than one at 36 hours. This was a small study reporting a moderate sensitivity and specificity of the colonic transit study; its findings need to be validated.
In a review on radionuclide gastro-esophageal motor studies, Mariani et al (2004) noted that radionuclide transit/emptying scintigraphy provides a means of characterizing exquisite functional abnormalities with a set of low-cost procedures that are easy to perform and widely available, entail a low radiation burden, closely reflect the physiology of the tract under evaluation, are well-tolerated and require minimum cooperation by patients, and provide quantitative data for better inter-subject comparison and for monitoring response to therapy. Despite the relatively low-degree of standardization both in the scintigraphic technique per se and in image processing, these methods have shown excellent diagnostic performance in several function or motility disorders of the upper digestive tract. Dynamic scintigraphy with a radioactive liquid or semi-solid bolus provides important information on both the oropharyngeal and the esophageal phases of swallowing, thus representing a useful complement or even a valid alternative to conventional invasive tests (e.g., stationary esophageal manometry) for evaluating abnormalities of oropharyngo-esophageal transit. Clinical applications of esophageal transit scintigraphy include disorders such as nutcracker esophagus, esophageal spasm, non-cardiac chest pain of presumed esophageal origin, achalasia, esophageal involvement of scleroderma, and gastro-esophageal reflux and monitoring of response to therapy. Scintigraphy with a radiolabeled test meal represents the gold standard for evaluating gastric emptying, whereas more recent radionuclide methods include dynamic antral scintigraphy and gastric SPECT for assessing gastric accommodation. Clinical applications of gastric-emptying scintigraphy include, among others, evaluation of patients with dyspepsia and evaluation of gastric function in various systemic diseases affecting gastric emptying.
Maurer and Parkman (2006) stated that nuclear medicine offers a variety of studies for evaluating motility throughout the gastro-intestinal tract. Gastric emptying remains the "gold standard" for studying gastric motor function, but its application in most centers remains limited to measuring only total gastric emptying in spite of data that show assessment of both fundal and antral function is of clinical value for evaluating patients with dyspepsia. Smith and Ferris (2003) noted that the diagnosis of diabetic gastroparesis may be confirmed by demonstrating gastric emptying delay during a 4-hr scintigraphic study. This is in agreement with the report by Stassen (2005) who noted that the diagnosis of diabetic gastroparesis may be confirmed by scintigraphy assessment of gastric emptying, preferably using a solid meal. Feigenbaum (2006) stated that the gold standard for the diagnosis of gastroparesis is a gastric emptying study. Furthermore, the AGA's medical position statement on diagnosis and treatment of gastroparesis (Parkman et al, 2004) stated that gastric emptying scintigraphy of a radiolabeled solid meal is the best accepted method to test for delayed gastric emptying.
Ziessman and associates (2009) examined if a study of clear liquid gastric emptying has added value for the diagnosis of gastroparesis over a study of solid emptying alone. A total of 101 patients underwent both solid and liquid gastric-emptying studies, acquired sequentially on the same day. A 30-min (1-min frames) liquid study (300 ml of water with 7.4 MBq [0.2 mCi] of (111) In-diethylenetriaminepentaacetic acid) was followed by a standardized 4-hr solid-meal study (a (99m)Tc-sulfur colloid-labeled egg-substitute sandwich meal). Emptying was quantified as a best-fit exponential emptying rate (T1/2) for liquids and percentage emptying at 4 hours for solid emptying. A total of 30 healthy volunteers underwent a study of clear liquid emptying to establish normal values. The results of the liquid and solid studies were compared. (111) In liquid down-scatter into the subsequent (99m)Tc solid meal results was analyzed. The upper range of normal for clear liquid emptying (T1/2) for healthy volunteers was 22 mins (mean +/- 3 SDs) and 19 mins (mean +/- 2 SDs). Of 101 patients, delayed emptying was found in 36% of liquid and 16% of solid studies. Of all patients with normal solid emptying, 32% had delayed liquid emptying. (111) In down-scatter into the (99m)Tc window was not generally significant. The authors concluded that for the detection of gastroparesis, a 30-min study of clear liquid gastric-emptying has considerable added diagnostic value over a study of solid emptying alone.
Hyett et al (2009) evaluate the prognostic value of gastric emptying studies on the morbidity associated with diabetic gastroparesis. This was a parallel cohort study of 3 groups. Group A (n = 94) contained diabetics (type 1 and type 2) with classic symptoms of gastroparesis (including early satiety, post-prandial fullness, bloating, abdominal swelling, nausea, vomiting, and retching) and delay in radionucleotide gastric emptying study. Group B (n = 94) contained diabetic subjects with classic symptoms of gastroparesis but negative scintigraphy. Group C (n = 94) contained diabetic subjects without symptoms of gastroparesis. Data were gathered on the number of days hospitalized and hospitalizations, office visits, emergency department (ED) visits, death rate, glycosylated hemoglobin levels (HbA1c), medications and past medical history. Group A had significantly more hospital days per 1,000 patient days (25.5) than both Group B (5.1; p < 0.01) and Group C (2.3; p < 0.01). Group A also had significantly more hospitalizations, office visits and ED visits than both Group B and Group C. Deaths and mean HbA1c level did not differ between the groups. Group A patients were more likely to have cardiovascular disease (19.2% versus 6.4% A versus C; p < 0.05), hypertension (63% versus 43% A versus C; p = 0.005) and retinopathy (33% versus 11.7% A versus C; p < 0.001). The authors concluded that a delayed radionucleotide gastric emptying study predicts negative health outcomes in diabetics with symptoms of gastroparesis. They identified a correlation between diabetic gastroparesis and cardiovascular disease, hypertension and retinopathy which may indicate an underlying vascular etiology.
Tipnis et al (2012) compared oro-anal transit time (OTT) measured by radio-opaque markers with colon motility (CM) findings in children with chronic constipation and evaluated clinical outcomes in children with chronic constipation evaluated by OTT and CM studies. A total of 24 children with chronic constipation (12 girls; median age of 12 years [3 to 18 years]; median symptoms of 87 months [6 to 186 months]) who underwent OTT and CM studies were reviewed. The OTT was determined using commercially available Sitzmarks. Patients were studied for a median of 23 months (4 to 60 months) and outcomes reviewed. All 5 children with normal OTT had normal CM; however, only 47% (9/19) of children with slow OTT had an abnormal CM. The abnormal CM findings were total colonic pseudo-obstruction in 3 and left colonic pseudo-obstruction in 6 children. Of the 9 children with abnormal CM, 5 were managed surgically, 1 with medicine escalation, and 3 were lost to follow-up; all 6 children with known follow-up have more bowel movements and less soiling. Of the 15 children with normal CM, 10 were managed with medication escalation, 3 with behavioral intervention, and 2 surgically. Of these 15 children, 8 improved, 1 did not change, 2 worsened, and 4 were lost to follow-up. The authors concluded that OTT studies may be helpful to predict which children should be referred for CM studies. Normal OTT studies may predict normal colon manometry; however, abnormal OTT studies may not predict abnormalities in colonic manometry in children with chronic constipation. Therefore, patients with slow transit marker studies should be assessed by colon manometry to evaluate colon neuromuscular integrity. This study did not evaluate the impact of colon manometry for patient management or disease outcomes.
Conklin (2013) stated that for several decades esophageal manometry has been the test of choice to evaluate disorders of esophageal motor function. The recent introduction of high-resolution manometry for the study of esophageal motor function simplified performance of esophageal manometry, and revealed previously unidentified patterns of normal and abnormal esophageal motor function. Presentation of pressure data as color contour plots or esophageal pressure topography led to the development of new tools for analyzing and classifying esophageal motor patterns. The current standard and still developing approach to do this is the Chicago classification. The author concluded that while this methodical approach is improving the diagnosis of esophageal motor disorders, it currently does not address all motor abnormalities.
Vela (2014) stated that treatment options for achalasia include oral pharmacologic therapy, endoscopic injection of botulinum toxin, pneumatic dilation, and myotomy (conventionally by laparoscopy, but more recently by an endoscopic approach). Oral pharmacologic agents have fallen out of use because of insufficient efficacy and frequent side effects. Endoscopic injection of botulinum toxin is safe and has good short-term effectiveness, but as the effect invariably wears off after a few months, this treatment is reserved for patients who are not candidates for more definitive treatments. Pneumatic dilation and surgical myotomy are currently considered the most effective treatments, with similar effectiveness in randomized controlled trials (RCTs) with follow-up of up to 2 years. The risk/benefit ratio and choice of therapy depend on patient characteristics (e.g., age, co-morbidities, disease stage, prior treatments), patient's preference, and locally available expertise. Treatment of patients who fail or relapse after initial therapy is challenging and the success rate of pneumatic dilation or myotomy in this group is lower compared with previously untreated patients. The recently developed per-oral endoscopic approach to myotomy has achieved excellent results in early uncontrolled studies, but high-quality RCTs are needed to ensure widespread adoption is reasonable. The authors also noted that retrospective data suggested that achalasia subtypes as defined by HREPT may guide treatment choice, but confirmation in prospective outcome studies is awaited.
Rao et al (2011) noted that scintigraphy is recommended for detection of altered small intestinal transit in subjects with suspected diffuse GI motility disorder but is available in a limited number of centers.
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM)’s practice guideline for small-bowel and colon transit (Maurer et al, 2013) noted that "A position paper from the American Neurogastroenterology and Gastrointestinal Motility Society and the European Society of Neurogastroenterology and Motility states that scintigraphy is recommended for "detection of altered small-intestine transit in subjects with suspected diffuse gastrointestinal motility disorder" and that colon transit scintigraphy "offers reproducible and accurate performance," as it measures whole-gut and regional colon transit in patients with suspected colonic motility disorders or more diffuse disorders involving the stomach or small intestine".
Kuribayashi et al (2015) note that recently reported normal values for esophageal motility obtained by high-resolution manometry (HRM) using a system with a Unisensor catheter were significantly different from those obtained by the ManoScan, which could result in a wrong diagnosis. To clarify whether these differences were due to system or subject differences, these investigators compared the manometric parameter values between ManoScan and a new system with a Unisensor catheter (Starlet) in the same subjects. A total of 103 volunteers without any symptoms related to esophageal motility disorders were recruited. Esophageal HRM was performed using both the ManoScan and the Starlet in all subjects. Data from the ManoScan were analyzed using ManoView, and data from the Starlet were analyzed by a program with e-sleeve function. Integrated relaxation pressure, distal contractile integral, contractile front velocity (CFV), intra-bolus pressure, and distal latency were calculated by both analyzing programs, and the values of these parameters were compared between the 2 systems by a signed rank test. Data from a total of 97 participants were analyzed. The values of all parameters, except CFV, measured by the Starlet were significantly higher than those obtained by the ManoScan (p < 0.01). The authors concluded that both systems can measure esophageal motility appropriately; nevertheless, they confirmed that the 2 systems showed different values of the parameters defined by the Chicago criteria; these differences should be recognized to evaluate esophageal motility precisely.
Herregods et al (2015) stated that esophageal HRM has rapidly gained much popularity worldwide. The Chicago Classification for esophageal motility disorders is based on a set of normative values for key metrics that was obtained using one of the commercially available HRM systems. Thus, it is of great importance to evaluate whether these normative values can be used for other HRM systems as well. In this review, these investigators described the presently available HRM systems, the currently known normative thresholds and the factors that influence them, and evaluated the use of these thresholds. Numerous factors including the type of HRM system, demographic factors, catheter diameter, body position during testing, consistency of bolus swallows, and esophageal length have an influence on the normative data. It would thus be ideal to have different sets of normal values for each of these factors, yet at the moment the amount of normative data is limited. The authors suggested broadening the normal range for parameters, as this would allow abnormal values to be of more significance. In addition, they suggested conducting studies to examine the physiological relevance of abnormal values and stress that for each system different normative thresholds may apply.
The American College of Gastroenterology’s clinical guideline on "Management of gastroparesis" (Camilleri et al, 2013) noted that "Alternative approaches for assessment of gastric emptying include wireless capsule motility testing and 13C breath testing using octanoate or spirulina incorporated into a solid meal; they require further validation before they can be considered as alternates to scintigraphy for the diagnosis of gastroparesis". (Conditional recommendation, moderate level of evidence).
3D High-Resolution Manometry for Quantification of Esophago-Gastric Junction Contractility
Lin and colleagues (2017) stated that the esophago-gastric junction (EGJ) is a complex sphincter composed of both the crural diaphragm (CD) and lower esophageal sphincter (LES). Three dimensional high-resolution manometry (3D-HRM) provides a dynamic 360 degrees representation of EGJ pressure in which the CD has a distinct pressure signature. These researchers developed 3D-HRM metrics to quantify the vigor of CD contractility, best eliminate the CD contribution and thereby isolate the LES component of EGJ contractility, and compare these metrics with conventional HRM metric of EGJ contractility. A total of 20 healthy subjects underwent 3D-HRM studies; 2 novel 3D-HRM EGJ metrics, 3D-DHA , and 3D-LES pressure (3D-LESP) were devised and calculated to best approximate the CD and LES components of the composite EGJ pressure topography. These values were then compared to conventional HRM metrics of EGJ contractility, the EGJ contractile integral (EGJ-CI), inspiratory EGJ pressure and expiratory EGJ pressure. Mean 3D-DHA correlated most strongly with EGJ-CI (r = 0.82, p < 0.001), while the 3D-LESP correlated most strongly with inspiratory EGJ pressure (r = 0.91 p < 0.001) and expiratory EGJ pressure (r = 0.85, p < 0.001). The authors devised novel 3D-HRM metrics to quantify the CD (3D-DHA ) and LES (3D-LESP) elements of EGJ contractility. Both measures correlated strongly with conventional HRM metrics of EGJ contractility. The 3D-DHA , in particular, correlated strongly with the EGJ-CI suggesting that both are largely determined by CD contractility. These researchers hoped that future studies will show these new metrics useful in quantifying elements of the anti-reflux barrier in mechanistically defined subsets of GERD patients.
Guillaumot and associates (2020) described the three-dimensional (3D) high-resolution esophageal manometry (HREM) patterns of achalasia. These investigators retrospectively included all consecutive patients who underwent 3D-HREM before and after treatment (pneumatic dilatation or per-oral endoscopic myotomy [POEM]) for achalasia between November 2016 and July 2017. The distribution of the pressures at the EGJ on 3D-HREM was determined; a total of 18 patients were included. Mean integrated relaxation pressure was 20.7 mmHg, and median (range) Eckardt score was 7 (4 to 10); 9 patients were treated by pneumatic dilatation and 7 by POEM; 9 patients underwent 3D-HREM after treatment. Before treatment, the EGJ pressure distribution was best observed at end expiration and during the 4 s of the integrated relaxation pressure measurement. During the integrated relaxation pressure, the LES was asymmetric in 12 patients with a high-pressure zone between the left and the posterior side of the EGJ. After treatment, 5 patients had a residual high-pressure point on the left or the posterior side of the EGJ. The authors concluded that 3D-HREM allowed a simple assessment of the pressure topography at the EGJ. In patients with achalasia, these researchers found the EGJ pressure to be asymmetric with a peak pressure on the greater curvature side. These researchers stated that 3D-HREM has the potential to guide initial and redo treatments.
Singendonk and colleagues (2020) noted that HREM, derived esophageal pressure topography (EPT) metrics, integrated relaxation pressure (IRP), and distal latency (DL) are influenced by age and size. Combined pressure and intraluminal impedance also allow derivation of metrics that define distension pressure and bolus flow timing. These researchers prospectively examined the effects of esophageal length on these metrics to determine if adjustment strategies are required for children. A total of 55 children (12.3 ± 4.5 years) referred for HREM, and 30 healthy adult volunteers (46.9 ± 3.8 years) were included. Studies were performed using the MMS system and a standardized protocol including 10 × 5 ml thin liquid bolus swallows (SBM kit, Trisco Foods) and analyzed via Swallow Gateway (www.swallowgateway.com). Esophageal distension pressures and swallow latencies were determined in addition to EGJ resting pressure and standard EPT metrics. Effects of esophageal length were examined using partial correlation, correcting for age. Adult-derived upper limits were adjusted for length using the slopes of the identified linear equations. Mean esophageal length in children was 16.8 ± 2.8 cm and correlated significantly with age (r = 0.787, p = 0.000). Shorter length correlated with higher EGJ resting pressure and 4-s integrated relaxation pressures (IRP), distension pressures, and shorter contraction latencies. Ten patients had an IRP above the adult upper limit. Adjustment for esophageal length reduced the number of patients with elevated IRP to 3. The authors prospectively confirmed that certain EPT metrics, as well as potential useful adjunct pressure-impedance measures such as distension pressure, were substantially influenced by esophageal length and required adjusted diagnostic thresholds specifically for children. These researchers stated that the findings of this study suggested that analytical software could be up-graded with automated age adjustment of diagnostic thresholds specifically for pediatric patients; further research is needed to determine normative thresholds to support pediatric use of the other manometric systems in current use.
The authors stated that this study had several drawbacks. First, due to ethical considerations, these researchers included a heterogeneous cohort of pediatric patients referred for HREM, rather than asymptomatic pediatric controls (not ethically possible). The study population was predominantly comprised of GERD patients, who typically displayed normal or minor esophageal motor disorders, and thus were the most ideal patient population to include for a study of this nature. Some patients were post-esophageal atresia repair, and some were post-fundoplication; these patients were included as these investigators hypothesized that their esophagus would achieve normal growth after surgery. Additional analyses revealed that their results did not lie outside the overall distribution and therefore did not skew the data-set. Additionally, as the clinical relevance of a diagnosis of IEM remains a matter of current debate, the authors did not exclude controls with IEM as they appeared to have the same symptom profile and barium study findings as patients with normal motility according to the Chicago Classification (CC) framework. This study was neither designed nor powered to explore more complex associations among HREM metrics, clinical symptoms (e.g., dysphagia), and other tests (e.g., pH‐MII monitoring), and this remained a topic for further prospective research in larger more homogeneous data-sets. The youngest patient able to tolerate the procedure and swallow 5-ml boluses was 1 year of age. Obtaining useful HREM data in the very young is challenging as it requires them to tolerate the procedure and repeat‐swallow on command. These researchers stated that further studies are needed to establish a standardized protocol and relevant criteria for patients less than 1 year of age.
Body Surface Gastric Mapping (Gastric Alimetry) for Evaluations of Gastric Motility/Gastroduodenal Disorders
Gharibans et al. (2018) sought to address the technical limitations of traditional electrogastrography (EGG), particularly the challenge of signal artifacts and inconsistent results from single-channel recordings, by developing a wearable multi-channel system with advanced artifact rejection methods for continuous, noninvasive measurement of gastric myoelectric activity in ambulatory subjects. The researchers recruited 11 subjects and compared the performance of their system to the clinical gold standard, gastric manometry. They implemented novel signal processing techniques to identify and remove artifacts, thereby improving the reliability of the EGG recordings. The results demonstrated a significant improvement in the correlation between EGG and manometry, with the mean correlation coefficient increasing by 0.56 (p < 0.001). The system enabled continuous ambulatory monitoring, revealing physiologically relevant patterns such as meal-induced changes in gastric myoelectric activity and circadian oscillations. The study concluded that this approach is noninvasive, easy to administer, and has the potential to expand the clinical utility of gastric myoelectric monitoring for diagnosis and management of gastrointestinal disorders. However, limitations include the relatively small sample size and the focus on healthy subjects, which may limit generalizability to broader patient populations. Additionally, while the artifact rejection methodology improved signal quality, further validation in diverse clinical settings and in patients with known motility disorders is needed to fully establish its diagnostic value.
Gharibans et al (2018) sought to develop and validate a noninvasive, continuous method for measuring gastric myoelectric activity in ambulatory subjects, addressing limitations of traditional electrogastrography (EGG) such as poor signal quality and susceptibility to motion artifacts. Researchers introduced a wearable multi-channel EGG system combined with an automated artifact rejection algorithm based on linear minimum mean squared error estimation. Validation was performed by comparing EGG recordings to gastric manometry, the clinical gold standard, in 11 pediatric subjects. Results showed that optimized electrode placement and artifact removal significantly improved signal quality, increasing the percentage of normal gastric slow-wave activity from 50% to 90% and enhancing correlation with manometry from near zero to a mean r-value of 0.57. Ambulatory recordings over 24 hours in a healthy adult demonstrated physiologic patterns, including postprandial increases in gastric activity lasting 3–4 hours and circadian-related frequency modulation. Limitations include the small sample size, use of pediatric subjects for validation due to clinical constraints, and reliance on manometry, which itself has limitations such as catheter migration and inability to detect all motility patterns. Further studies with diverse populations and additional validation against other clinical standards are needed to confirm generalizability and refine the technology.
Gharibans et al (2019) aimed to determine whether spatial abnormalities in gastric slow-wave activity, as measured by noninvasive high-resolution electrogastrography (HR-EGG), correlate with symptom severity in patients with functional dyspepsia and gastroparesis. The investigators conducted a case-control study involving 32 subjects: 7 healthy controls, 7 with functional dyspepsia and normal gastric emptying, and 18 with gastroparesis. All participants underwent abdominal CT imaging to guide precise HR-EGG array placement, completed the PAGI-SYM symptom questionnaire, and had gastric emptying assessed. The results showed that 44% of symptomatic patients exhibited spatial slow-wave abnormalities, and a higher proportion of slow waves with aberrant propagation direction was significantly associated with greater total gastroparesis cardinal symptom index scores (r = 0.56, P < .001) and more severe abdominal pain (r = 0.46, P = .009). Notably, traditional EGG parameters did not correlate with symptoms. The study concluded that gastric myoelectric dysfunction, as detected by HR-EGG, may contribute to symptom genesis in these disorders, and that spatial HR-EGG parameters correlate with symptom severity independent of gastric emptying. Limitations include the small sample size, single-center design, and the need for further validation to establish clinical utility and generalizability of HR-EGG findings in broader patient populations.
Gharibans et al (2022) stated that chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction; however, clinical tests for objectively defining gastric motor function are lacking. A medical device enabling non-invasive body surface gastric mapping (BSGM) was developed and used to examine NVS pathophysiology. BSGM was carried out in 43 patients with NVS and 43 matched controls using Gastric Alimetry (GA), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging App. Continuous measurement encompassed a fasting baseline (30 mins), 482-Kcal meal, and 4-hour post-prandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median of 23.3 microvolts versus 38.0 microvolts, p < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, p = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; p < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all p > 0.05). Most patients (62%) had normal BSGM studies with increased psychological co-morbidities (43.5% versus 7.7%; p = 0.03) and anxiety scores (median of 16.5 versus 13.0; p = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r > 0.35, p < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlated with symptoms, which should inform clinical management and therapeutic trial design. The authors concluded that this study introduced a novel medical device for BSGM and showed its use in a study of NVS patients who shared common symptom profiles but reveal distinct phenotypes. These findings could improve clinical management of NVS patients by separating those with gastric dysfunction from those with gut-brain dysregulation or other etiologies.
The authors stated that this study had several drawbacks. First, although specific criteria were employed, using a consensus panel classification introduced subjectivity that could limit reproducibility; therefore, BSGM reference ranges are being established to promote standardized reporting. Second, classifications were conservative, being based primarily on meal responses and gastric rhythm, and patients with borderline tests (e.g., isolated high stable frequencies and transient abnormalities) were currently classed as negative. As more data becomes available, it will be possible to refine the classification scheme, and together with emerging spatial metrics, this should increase discriminative power. Third, the study population included both diabetic as well as idiopathic patients, and while a subgroup analysis was carried out showing no differences in BSGM test metrics, larger dedicated studies would be desirable to compare these groups in future. Fourth, while blood glucose levels were not continuously recorded in this study, recent data from a separate BSGM study in long-term diabetics has indicated that blood glucose levels did not appear to correlate with the electrophysiological abnormalities reported here. Recent data showed day-to-day fluctuations in blood glucose did not influence gastric emptying, with diabetic gastroparesis potentially representing a distinct subset with more reproducible emptying derangements than others, although further research on this subject would be valuable given the potential dysrhythmic effects of hyperglycemia.
Calder, et al. (2022) aimed to address the challenge of artifact contamination in body surface gastric mapping (BSGM), a high-resolution technique for assessing gastric myoelectrical activity. The investigators developed and validated an automated artifact detection and rejection algorithm for clinical BSGM applications. Ten patients with chronic gastric symptoms generated a variety of artifacts using a standardized protocol, resulting in 176 recordings with a commercial BSGM system. The algorithm’s performance was compared against a reference standard of consensus expert labeling, as well as assessments by six clinicians (three untrained, three trained in artifact detection). Inter-rater reliability was high among experts (Fleiss' kappa 0.84), untrained clinicians (0.76), and trained clinicians (0.71). The algorithm demonstrated sensitivity and specificity exceeding 95% compared to expert markers, outperforming both untrained and trained clinicians in sensitivity while maintaining high specificity. The main limitation of the study is its relatively small sample size and the use of a single commercial system, which may affect generalizability to broader clinical settings or other BSGM platforms. Additionally, the artifact generation protocol may not encompass the full spectrum of real-world artifacts encountered in diverse patient populations. The authors concluded that, overall, the study provides strong evidence that automated artifact detection can reliably improve the clinical utility of BSGM by overcoming a key barrier to accurate test interpretation.
Xu et al (2022) defined phenotypes of gastric myoelectrical abnormalities and relation to symptoms in individuals with longstanding type 1 diabetes mellitus (T1DM), compared to matched healthy controls, using a novel non-invasive BSGM device. BSGM was carried out on individuals with T1DM of over 10 years duration and matched controls, employing Gastric Alimetry. A total of 32 individuals with T1DM were recruited (15 with a high symptom burden), and 32 controls. Those with symptoms showed more unstable gastric myoelectrical activity, (Gastric Alimetry Rhythm Index 0.39 versus 0.51, p = 0.017; and lower average spatial co-variance 0.48 versus 0.51, p = 0.009) compared with controls. Those with T1DM and symptoms also had higher prevalence of peripheral neuropathy (67% versus 6%, p = 0.001), anxiety/depression diagnoses (27% versus 0%, p = 0.001), and mean HbA1c levels (76 versus 56 mmol/mol, p < 0.001). BSGM defined distinct phenotypes in subjects including those with markedly unstable gastric rhythms (4/32, 12.5%), and abnormally high gastric frequencies (10/32, 31%). Deviation in gastric frequency was positively correlated with symptoms of bloating, upper gut pain, nausea and vomiting, and fullness and early satiation (r > 0.35, p < 0.05). The authors concluded that gastro-duodenal symptoms in individuals with long-standing T1DM correlated with gastric myoelectrical abnormalities on BSGM evaluation, in addition to glycemic control, psychological co-morbidities, and peripheral neuropathy. BSGM using the Gastric Alimetry device identified a range of myoelectrical phenotypes, representing both myogenic and neurogenic mechanisms, which represent targets for diagnosis, monitoring and therapy.
Gharibans et al (2023) stated that disorders of gastric function are highly prevalent; however, diagnosis often remains symptom-based and inconclusive. These investigators stated that BSGM is an emerging diagnostic solution, but current approaches lack scalability and are cumbersome and clinically impractical. These researchers presented a novel scalable system for non-invasively mapping gastric electrophysiology in high-resolution at the body surface. The system comprises a custom-designed stretchable high-resolution "peel-and-stick" sensor array (8 × 8 pre-gelled Ag/AgCl electrodes at 2 cm spacing; area 225 cm2), wearable data logger with custom electronics incorporating bio-amplifier chips, accelerometer and Bluetooth synchronized in real-time to an App with cloud connectivity. Automated algorithms filter and extract HR biomarkers including propagation (phase) mapping. The system was tested in a cohort of 24 healthy subjects to define reliability and characterize features of normal gastric activity (30-min fasting, standardized meal, and 4 hours post-prandial). Gastric mapping was successfully achieved non-invasively in all cases (16 male; 8 female; age of 20 to 73 years; BMI 24.2 ± 3.5). In all subjects, gastric electrophysiology and meal responses were successfully captured and quantified non-invasively (mean frequency 2.9 ± 0.3 cycles/min; peak amplitude at a mean of 60 mins post-prandially with return to baseline in less than 4 hours). Spatio-temporal mapping showed regular and consistent wave activity of mean direction 182.7° ± 73 (74.7% antegrade, 7.8% retrograde, 17.5% indeterminate). The authors concluded that BSGM is a new diagnostic tool for evaluating gastric function that is scalable and ready for clinical applications, offering several biomarkers that are improved or new to gastroenterology practice.
The authors stated that signal processing and analysis methods remain in ongoing development. A recent technical paper has validated the accuracy of BSGM in measuring the propagation direction of individual wave-fronts at the body surface with direct reference to simultaneous high‐resolution serosal mapping, using similar techniques to those applied here. This study provided confidence that the technique is reliable, while also paving the way for future studies that provide more granular data on individual wave direction throughout entire recordings. This step will also enable temporal correlations between symptom onset and retrograde wave patterns, in order to further elucidate the emerging clinical significance of retrograde gastric propagation. These researchers stated that further investigation to introduce and validate artifact identification schemes would be valuable. Furthermore, modeling and bench‐top studies also suggest that it may be possible in future to identify more complex wave patterns that occur in the stomachs of patients (e.g., colliding wave-fronts, conduction blocks and re‐entrant activity), although this has not yet been validated experimentally. An additional drawback was that this study was carried out in healthy subjects of normal weight, and the reliability of the system requires further validation in obese subjects. Previously, Gharibans et al (2018) have shown the ability to measure BSGM data up to a BMI of at least 35, which was, therefore, applied as the cut‐off here.
Varghese et al (2023a) noted that the Gastric Alimetry platform offers a multi-modal assessment of gastric function via BSGM and concurrent symptom-tracking via a validated App. These researchers carried out a longitudinal cohort study to examine the impact of Gastric Alimetry, and changes in clinical management on patient symptoms, QOL, and psychological health. This is a prospective, longitudinal, observational, multi-center study of participants with chronic gastro-duodenal symptoms. Consecutive participants undergoing Gastric Alimetry will be invited to participate. QOL will be assessed via EuroQol-5D and the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score. GI symptoms will be assessed via the Patient Assessment of Upper Gastrointestinal Symptom Severity index, and the Gastroparesis Cardinal Symptom Index. Psychometrics will be assessed, including anxiety via the General Anxiety Disorder-7, perceived stress using the Perceived Stress Scale 4, and depression via the Patient Health Questionnaire 9. Clinical parameters including diagnoses, investigations, and treatments (medication and procedures) will also be captured. Assessments will be made the week after the BSGM test, at 30 days, 90 days, 180 days, and 360 days thereafter. The primary outcome is feasibility of longitudinal follow-up of a cohort that have undergone Gastric Alimetry testing; from which patients' continuum of care can be characterized. Secondary outcomes include changes in patient-reported symptoms, QOL, and psychometrics (anxiety, stress, and depression). Inferential causal analyses will be carried out at the within patient level to examine causal associations between treatment changes and clinical outcomes. The impact of Gastric Alimetry on clinical management will also be captured. These researchers stated that these data will offer insight into the clinical utility and impact of Gastric Alimetry, a new test to gastroenterology practice, and offer data to test hypotheses in relation to impact on clinical decisions, treatment responses, and natural histories of disease.
Varghese et al (2023b) noted that chronic gastro-duodenal symptoms are often overlapping within existing diagnostic paradigms and current diagnostic tests are insensitive to underlying pathophysiology. These investigators stated that Gastric Alimetry has emerged as a new diagnostic test of gastric neuromuscular function with time-of-test symptom profiling. They examined the impact to diagnosis and healthcare utilization following the introduction of Gastric Alimetry into clinical care. Consecutive data from 2 tertiary centers with chronic gastro-duodenal symptoms (Rome-IV defined, or motility disorder), having integrated care and Gastric Alimetry testing were evaluated. Changes in diagnoses, interventions, and management were quantified. Pre- and post-test healthcare utilization was reported. A preliminary management framework was established through experiential learning. A total of 50 participants (45 women; median age of 30 years; 19 with gastroparesis, 25 with CNVS, and 7 with functional dyspepsia [FD]) underwent Gastric Alimetry testing; 1/3 of patients had a spectral abnormality (18% dysrhythmic/low-amplitude). Of the remainder, 9 had symptoms correlating to gastric amplitude, while 19 had symptoms unrelated to gastric activity. Gastric Alimetry aided management decisions in 84%, including changes in invasive nutritional support in 9/50 cases (18%; predominantly de-escalation). Healthcare utilization was significantly lower post-Gastric Alimetry testing (mean of $39,724, SD ± 63,566 versus $19,937, SD ± 35,895, p = 0.037). The authors concluded that Gastric Alimetry aided diagnosis and management of patients with chronic gastro-duodenal symptoms by enabling phenotype-informed care. The high majority of tests aided management decisions, which was associated with reduced healthcare utilization.
Varghese et al (2023c) noted that BSGM is a new non-invasive test of gastric function. BSGM offers several novel and improved biomarkers of gastric function capable of differentiating patients with overlapping symptom profiles. These researchers defined normative reference intervals for BSGM spectral metrics in a population of healthy controls (HCs). BSGM was performed in HCs using GA comprising a stretchable high-resolution array (8 × 8 electrodes; 196 cm2), wearable Reader, and validated symptom-logging App. The evaluation encompassed a fasting baseline (30 mins), 482 kCal meal, and 4-hour post-prandial recording. Normative reference intervals were calculated for BSGM metrics including the Principal Gastric Frequency, GA Rhythm Index (a measure of the concentration of power in the gastric frequency band over time), body mass index (BMI)-adjusted amplitude (μV), and fed:fasted amplitude ratio. Data were reported as median and reference interval (5th and/or 95th percentiles). A total of 110 subjects (55% women, median age of 32 years [inter-quartile range [IQR] 24 to 50), median BMI 23.8 kg/m 2 (IQR 21.4 to 26.9) were included. The median Principal Gastric Frequency was 3.04 cycles/min; reference interval: 2.65 to 3.35 cycles/min. The median GA Rhythm Index was 0.50; reference interval: greater than or equal to 0.25. The median BMI-adjusted amplitude was 37.6 μV; reference interval: 20 to 70 μV. The median fed:fasted amplitude ratio was 1.85; reference interval of greater than or equal to 1.08. A higher BMI was associated with a shorter meal-response duration (p = 0.014). The authors concluded that this study provided normative reference intervals for BSGM spectral data to inform diagnostic interpretations of abnormal gastric function.
Varghese et al (2023d) stated that gut dysmotility is an increasingly common contributor to intestinal failure; however, differentiating true cases of severe dysmotility requiring intensive nutritional support from other causes of symptoms (e.g., gut-brain or visceral hypersensitivity disorders) is clinically challenging. Reliable motility tests are not widely accessible and may be non-contributory, while transit studies can be labile and insensitive for neuromuscular pathologies. Gastric Alimetry is a new test of gastric function that was recently shown to define patient subgroups with neuromuscular dysfunction in CNVS. These investigators reported the 1st application of Gastric Alimetry to a cohort of adult patients established on parenteral nutrition (PN) for a possible GI motility disorder. A total of 10 patients with diagnostic uncertainty were evaluated, 9 on PN, 1 recently weaned due to a line infection. Gastric Alimetry evaluation was found to contribute to management decisions in all 10 cases, with clinical diagnoses being updated in 6/10, primarily to re-focus on disorders of gut-brain interaction in subjects with normal tests. Changed management based on test results facilitated successful weaning of PN in 6/9 patients at median 5 months of follow-up, due to effective targeted pharmacotherapy and integrated care. The authors concluded that these data supported the role of Gastric Alimetry in the work-up of possible intestinal failure patients with suspected motility disorders, with utility in diagnosis and management. Test results facilitated gut rehabilitation, reduced PN dependence; thus, reducing healthcare costs (estimated at greater than NZ$ 100,000 per PN patient per year in nutritional support alone).
Xu et al (2023) stated that CNVS, FD, and gastroparesis are complex disorders. BSGM, a new test of gastric function, using Gastric Alimetry may be useful for de-escalating healthcare utilization. These investigators defined healthcare costs and estimated health economic impacts of implementing this test in patients with chronic gastro-duodenal symptoms. Consecutive patients at a tertiary referral center examined with Gastric Alimetry were included. Frequency and cost data relating to medical investigations, hospital, and outpatient presentations were evaluated. Costs of healthcare utilization were calculated, and the potential cost savings of implementing Gastric Alimetry within a diagnostic decision-tree model were estimated. A total of 31 consecutive patients (mean age of 36.1 years; 83.9% female; predominant symptoms: nausea [83.9%], pain [61.3%], vomiting [67.7%], bloating [35.5%]) completed Gastric Alimetry testing. Repeat gastroscopy and abdominal CT rates were 29% (8/28) and 85% (11/13), respectively. Gastric Alimetry testing identified spectral abnormalities in 45.2% of patients, and symptom profiling classified a further 29.1% of patients. Median annualized cost difference after test introduction was NZ$ -12,032. Estimated reductions in investigation-related costs when incorporating Gastric Alimetry into the diagnostic workflow model were approximately NZ$ 1,500 per patient. The authors concluded that healthcare utilization and confirmatory testing rates remain high in nausea and vomiting syndromes. This study presented real-world data, together with a decision-tree analysis, showing Gastric Alimetry can streamline clinical care pathways, resulting in reduced healthcare utilization and cost.
Schamberg et al (2023) noted that EGG non-invasively evaluates gastric motility but is viewed as lacking clinical utility. Gastric Alimetry is a new diagnostic test that combines high-resolution BSGM with validated symptom profiling, with the objective of overcoming EGG's limitations. In a retrospective study, these researchers compared EGG and BSGM to define performance differences in spectral analysis. Comparisons between Gastric Alimetry BSGM and EGG were conducted by protocolized evaluation of 178 subjects (110 controls; 68 NVS and/or T1DM). Comparisons followed standard methodologies for each test (pre-processing, post-processing, analysis), with statistical evaluations for group-level differences, symptom correlations, and patient-level classifications. BSGM showed substantially tighter frequency ranges versus EGG in controls. Both tests detected rhythm instability in NVS, but EGG showed opposite frequency effects in T1DM. BSGM showed an 8x increase in the number of significant correlations with symptoms. BSGM accuracy for patient-level classification was 0.78 for patients versus controls; and 0.96 as compared to blinded consensus panel; EGG accuracy was 0.54 and 0.43. EGG detected group-level differences in patients, but lacked symptom correlations and showed poor accuracy for patient-level classification, explaining EGG's limited clinical utility. The authors concluded that BSGM showed substantial performance improvements across all domains.
The authors stated that there are several factors to be considered when interpreting these findings, especially as they relate to the existing EGG literature. First, EGG analysis was performed using an automated artifact detection algorithm. It was possible that manual approaches could have improved results, although the automated system used is well-validated against expert manual marking. Second, proprietary signal processing steps could be used in commercial EGG devices, which are not disclosed, and hence could not be implemented. Third, all tests were carried out using a standard 482 kCal meal, and other meals or water load tests have been applied in past EGG studies; however, these researchers selected this meal because their unpublished experience was that it generated a reliable electrophysiological response, whereas a water load did not. Fourth, these investigators only considered a single electrode configuration. This was based on EGG literature, although multi-channel EGG studies (e.g., up to 6 electrodes) have also been reported, and ultrasound (US) imaging has been used for antral localization. Presumably, the use of more channels would improve performance of the EGG pipeline, however, the authors’ simpler experimental setup matched current commercially-available systems. Fifth, all stages of the EGG processing pipeline required decisions on specific approaches for which there may not be unanimous consensus in the literature. More importantly, for all of the above considerations, the selected approach has been implemented uniformly across the entire cohort based on published guidance, with the objective of minimizing any biasing effect that could artificially impair the ability of EGG outputs to differentiate patients from controls. Finally, this trial focused only on spectral analyses of BSGM and EGG. While surface recordings are highly validated against invasive serosal recording, subtle abnormalities such as conduction blocks or stable ectopic pacemakers may not be captured by non-invasive techniques applying spectral metrics. Spatial analytics for non-invasive mapping are currently evolving, which could further improve the precision of BSGM and yield new phenotypes in the future. Moreover, use of gastric myoelectrical activity analyses for aiding in treatment and diagnosis of gastrointestinal disorders is supported by simultaneous evaluation of symptoms and complete patient medical history.
Doguet et al (2023) stated that GI potential mapping could be useful for examining GI motility disorders. Such disorders are found in inflammatory bowel diseases (IBDs), such as CD, or GI functional disorders. GI potential mapping data originate from a mixture of several GI electrophysiological sources (termed ExG) and other noise sources, including the electrocardiogram (ECG) and respiration. De-noising and/or source separation techniques are needed, however, with real measurements, no ground truth is available. These investigators proposed a framework for the simulation of body surface GI potential mapping data. The frame-work is an electrostatic model, based on fecgsyn tool-box, using dipoles as electrical sources for the heart, stomach, small bowel and colon, and an array of surface electrodes. It is shown to generate realistic ExG waveforms, which are then used to compare several ECG and respiration cancellation techniques, based on, fast independent component analysis (FastICA) and pseudo-periodic component analysis (PiCA). The best performance was obtained with PiCA with a median root mean squared error of 0.005.
Wang et al (2023) aimed to investigate gastric electrophysiology, symptoms, and quality of life in patients who had undergone pancreaticoduodenectomy (PD), using the non-invasive Gastric Alimetry system. Nineteen PD patients and nineteen matched healthy controls were assessed with high-resolution body-surface gastric mapping, symptom logging, and validated quality-of-life questionnaires. The protocol included a 30-minute fasting recording, a standardized reduced-volume meal, and a four-hour postprandial recording. Spectral metrics such as Principal Gastric Frequency, BMI-adjusted amplitude, Gastric Alimetry Rhythm Index, and fed-to-fasted amplitude ratio were analyzed against normative reference ranges and controls. Results showed no significant differences in gastric electrophysiology between PD patients and controls, although 8 of 19 patients exhibited mild deviations from reference intervals. Moderate to severe upper gastrointestinal symptoms were reported by 42% of patients, and quality-of-life scores were significantly worse than controls (p<0.01), but these did not correlate with electrophysiological abnormalities. Symptom phenotypes varied, suggesting multifactorial origins including gastric sensorimotor dysfunction, gut-brain axis disorders, and small bowel contributions. The study confirmed the safety and feasibility of Gastric Alimetry in this population. Limitations included the small sample size, potential selection bias, and the focus on long-term rather than early postoperative changes, which may have missed transient electrophysiological disturbances. Future research should explore pre- and early postoperative gastric function and its relationship to delayed gastric emptying and symptom development.
O'Grady et al (2023) noted that chronic gastric symptoms are common; however, differentiating specific contributing mechanisms in individual patients remains challenging. Abnormal gastric motility is present in a significant subgroup, but reliable methods for evaluating gastric motor function in clinical practice are lacking. Body surface gastric mapping is a new diagnostic aid employing multi-electrode arrays to measure and map gastric myoelectrical activity non-invasively in high resolution. Clinical adoption of BSGM is currently expanding following studies showing the ability to achieve specific patient subgrouping, and subsequent regulatory clearances. An international working group was formed in order to standardize clinical BSGM methods, encompassing a technical group developing BSGM methods and a clinical advisory group. The working group carried out a technical literature review and synthesis focusing on the rationale, principles, methods, and clinical applications of BSGM, with secondary review by the clinical group. The principles and validation of BSGM were evaluated, including key advances achieved over legacy electrogastrography (EGG). Methods for BSGM were reviewed, including device design considerations, patient preparation, test conduct, and data processing steps. Recent advances in BSGM test metrics and reference intervals were discussed, including 4 novel metrics, being the "principal gastric frequency", BMI-adjusted amplitude, Gastric Alimetry Rhythm Index, and fed:fasted amplitude ratio. An additional essential element of BSGM has been the introduction of validated digital tools for standardized symptom profiling, performed simultaneously during testing. Specific phenotypes identifiable by BSGM and the associated symptom profiles were codified with reference to pathophysiology. Finally, knowledge gaps and priority areas for future BSGM research were also identified by the working group.
Schamberg et al (2023) aimed to address technical limitations in traditional electrogastrography (EGG) spectral metrics by developing and validating improved metrics for body surface gastric mapping (BSGM). The authors critically evaluated five conventional EGG metrics – dominant frequency, percentage time normogastria, amplitude, power ratio, and instability coefficient – using a standardized database of 100 BSGM tests (30-minute baseline and 4-hour postprandial recordings with Gastric Alimetry). They identified significant pitfalls, such as strong correlation between BMI and amplitude, and misclassification of low-frequency transients as gastric activity, which compromised the reliability of traditional metrics. To overcome these issues, the study introduced four revised BSGM spectral metrics: BMI-adjusted amplitude, Principal Gastric Frequency, Gastric Alimetry Rhythm Index (GA-RI), and a Fed:Fasted Amplitude Ratio calculated over a 4-hour postprandial window. These revised metrics demonstrated improved performance, with reduced confounding and better discrimination of gastric activity. Limitations of the study include its reliance on a single device and database, which may affect generalizability, and the need for further validation in diverse patient populations and clinical settings. Overall, the revised metrics resolve critical pitfalls of legacy EGG analysis and are recommended for future BSGM spectral studies.
Du et al. (2024) aimed to quantify the effects of transcutaneous auricular vagus nerve stimulation (TaVNS) at different frequencies (10, 40, and 80 Hz) compared to sham stimulation on gastric myoelectrical activity in healthy adults following a water-load test. Eighteen volunteers underwent four sessions, each including baseline, TaVNS, water-load, and post-water-load periods, with body-surface gastric mapping and heart rate variability assessments. The results showed that TaVNS at all tested frequencies normalized water-load-induced gastric dysrhythmias, with 40- and 80-Hz protocols also increasing gastric amplitude and modulating autonomic function, specifically, increasing parasympathetic activity (RMSSD) and reducing sympathetic stress index (SI) at higher frequencies. The study concluded that TaVNS can effectively restore normal gastric myoelectrical rhythms in healthy subjects by influencing both parasympathetic and sympathetic pathways. However, the study's limitations include its small sample size, restriction to healthy individuals (limiting generalizability to patients with gastric disorders), and short-term assessment without evaluation of sustained effects or clinical outcomes. Additionally, the water-load test may not fully replicate pathological gastric dysrhythmias seen in disease states, and the crossover design could be subject to carryover effects. These factors suggest that while the findings are promising, further research in patient populations and with longer follow-up is needed to establish clinical relevance and optimal stimulation parameters.
Humphrey et al (2024) developed and validated a set of static and animated gastro-duodenal symptom pictograms for children. There were 3 study phases: Phase 1: co-creation using experience design methods to develop pediatric gastro-duodenal symptom pictograms (static and animated); phase 2: an online survey to evaluate acceptability, as well as face and content validity; and phase 3: a preference study. Phases 2 and 3 compared the novel pediatric pictograms with existing pictograms used with adult patients. A total of 8 children aged 6 to 15 years (5 female) participated in phase 1, and 69 children in phase 2 (median age of 13 years: IQR 9 to 15); an additional 49 participants were included in phase 3 (median age of 15: IQR 12 to 17). Face and content validity were higher for the pediatric static and animated pictogram sets compared with pre-existing adult pictograms (78% versus 78% versus 61%). Participants with worse gastric symptoms had superior comprehension of the pediatric pictograms (χ2 (8, n = 118) p < 0.001). All participants preferred the pediatric static pictogram set was over both the animated and adult sets (χ2 (2, n = 118) p < 0.001). The authors concluded that the co-creation phase resulted in the symptom concept confirmation and design of 10 acceptable static and animated gastro-duodenal pictograms with high face and content validity when evaluated with children aged 6 to 18 years. Validity was superior when children reported more problematic symptoms. These researchers stated that these pictograms could be used in clinical and research practice to enable standardized symptom reporting for children with gastro-duodenal disorders. Moreover, these investigators stated that further validation studies should be considered in pediatric patients with greater symptom burden, a larger younger population, diverse cultural and ethnic groups, as well as populations from different jurisdictions. They stated that validating the pictograms with more participants with experience of gastro-duodenal symptoms will enable concurrent and convergent validity studies to be undertaken.
Seo et al (2024) noted that abnormal cyclic motor pattern (CMP) activity is implicated in colonic dysfunction; however, the only tool to examine CMP activity, high-resolution colonic manometry (HRCM), remains expensive and not widely accessible. These researchers attempted to validate BSCM via direct correlation with HRCM. Synchronous meal-test recordings were carried out in asymptomatic participants with intact colons. A signal processing method for BSCM was developed to detect CMPs. Quantitative temporal analysis was conducted comparing the meal responses and motility indices (MI); spatial heat maps were also compared. Post-study questionnaires assessed participants' preference and comfort/distress experienced from either test. A total of 11 participants were recruited, and 7 had successful synchronous recordings (5 women/2 men; median age of 50 years [range of 38 to 63]). The best-correlating MI temporal analyses achieved a high degree of agreement (median Pearson correlation coefficient (Rp) value: 0.69; range of 0.47 to 0.77). HRCM and BSCM meal response start and end times (Rp = 0.998 and 0.83; both p < 0.05) and durations (Rp = 0.85; p = 0.03) were similar; and heat maps revealed good spatial agreement. The authors concluded that this study has shown 3 different metrics with validation that the resulting signal source from BSCM analysis was reliably of colonic origin: First, motility index correlations; second, meal response synchronicity; and third, spatial hotspot analysis. CMP hypo-activity or hyper-activity has been associated with the development of low anterior resection syndrome (LARS), fecal incontinence, post-operative ileus, and IBS, such that these newly validated BSCM biomarkers could serve to guide clinical therapies. This is especially significant because while HRCM remains an important research tool, it is not widely available, relatively invasive, and its data are time-consuming and complex to analyze. BSCM, on the other hand, may be performed without anesthesia nor endoscopy, and examines the colon in its physiologically natural/unprepped state for longer durations. These researchers stated that BSCM has significant potential to generate a meaningful mechanistic understanding of functional disorders and guide clinical therapies. Moreover, they noted that an important limitation of the BSCM technique is that the directions of wave propagation cannot yet reliably be ascertained due to the complex and variable anatomy of the colon.
The authors stated that one drawback of this trial was the small cohort size, which reflected the highly technical and challenging experimental technique that also poses difficulties to patient recruitment and through-put owing to the invasiveness of manometry, procedural stressors, and time factors, as well as COVID-related mandatory restrictions during the study period. However, together the data set is rich in that every case provided sufficient physiological and anatomical variations (frequency, regional activities, colonic anatomy, and manometer insertion depth) to inform an analysis pipeline of strong correlation which could be applied in future BSCM studies.
Lim et al (2024) sought to determine how the menstrual cycle and menopause affect human gastric electrophysiology. Using noninvasive Body Surface Gastric Mapping (BSGM) and a validated symptom logging app, the investigators compared premenopausal women in the follicular and luteal phases, postmenopausal women, and male controls. Key electrophysiological parameters analyzed included principal gastric frequency (PGF), BMI-adjusted amplitude, Gastric Alimetry Rhythm Index (GA-RI), and Fed:Fasted Amplitude Ratio (ff-AR). The study found that PGF was significantly higher in the luteal phase compared to the follicular phase and males, and postmenopausal women also had higher PGF, amplitude, GA-RI, and ff-AR than follicular-phase women and males. Computational modeling suggested these electrophysiological changes would result in increased gastric mixing and faster emptying in the luteal phase. Importantly, there were no significant differences in symptom burden across groups. Limitations include the cross-sectional design, which may not fully account for intra-individual variability, and the reliance on noninvasive mapping rather than direct measurement of gastric motility. The study also did not assess hormonal levels directly, and symptom assessment may have lacked sensitivity to subtle changes. Overall, the findings provide evidence for substantial variations in gastric electrophysiology related to menstrual cycling and menopause, but further research is needed to clarify clinical implications and underlying mechanisms.
Huang, et al. (2024) assessed varying meal size on BSGM responses to inform test use in a wider variety of contexts. Data from multiple healthy cohorts receiving BSGM were pooled, using four different test meals. A standard BSGM protocol was employed: 30-min fasting, 4-h post-prandial, using Gastric Alimetry® (Alimetry, New Zealand). Meals comprised: (i) nutrient drink + oatmeal bar (482 kcal; 'standard meal'); (ii) oatmeal bar alone; egg and toast meal, and pancake (all ~250 kcal). Gastric
Alimetry metrics included BMI-adjusted Amplitude, Principal Gastric Frequency, Gastric Alimetry Rhythm Index (GA-RI) and Fed:Fasted Amplitude Ratio (ff-AR). A total of 238 participants (59.2% female) were included. All meals significantly increased amplitude and frequency during the first postprandial hour (p < 0.05). There were no differences in postprandial frequency across meals (p > 0.05). The amplitude and GA-RI of the standard meal (n = 110) were significantly higher than the energy bar alone (n = 45) and egg meal (n = 65) (all p < 0.05). All BSGM metrics were comparable across the three smaller meals (p > 0.05). A higher symptom burden was found in the oatmeal bar group versus the standard meal and pancake meal (p = 0.01, 0.003, respectively). The investigators concluded that the consumption of lower calorie meals elicited different postprandial responses, when compared to the standard Gastric Alimetry meal. The investigators explained that these data will guide interpretations of BSGM when applied with lower calorie meals.
Wang et al (2024) stated that gastric emptying testing (GET) evaluates gastric motility; however, it is non-specific and insensitive for neuromuscular disorders. Gastric Alimetry is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling. These researchers examined patient-specific phenotyping using GA compared to GET. Patients with chronic gastro-duodenal symptoms underwent simultaneous GET and GA, comprising a 30-min baseline, 99m TC-labelled egg meal, and 4-hour post-prandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: sensorimotor; continuous; and other. A total of 75 patients were examined – 77% female. Motility abnormality detection rates were: GET 22.7% (14 delayed, 3 rapid); GA spectral analysis 33.3% (14 low rhythm stability / low amplitude; 5 high-amplitude; 6 abnormal frequency); combined yield 42.7%. In patients with normal spectral analysis, GA symptom phenotypes included: sensorimotor 17% (where symptoms strongly paired with gastric amplitude; median r = 0.61); continuous 30%; other 53%. GA phenotypes showed superior correlations with GCSI, PAGI-SYM, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores (p > 0.05). Delayed emptying was not predictive of specific GA phenotypes. The authors concluded that GA improved patient phenotyping in chronic gastro-duodenal disorders in the presence and absence of motility abnormalities with improved correlation with symptoms and psychometrics compared to gastric emptying status and Rome IV criteria. These researchers stated that these findings have implications for the diagnostic profiling and personalized management of gastro-duodenal disorders. It should be noted that this manuscript is a pre-print; and it has not yet been peer-reviewed by a journal.
The authors stated that this study had several drawbacks. First, although the protocols of the 2 tests were compatible, some compromises impacted optimal performance of the Gastric Alimetry test. Patients were asked to periodically mobilize between the scintigraphy table and waiting areas, introducing motion artifacts. These were able to be corrected or rejected using validated algorithms, mitigating their significance over a 4-hour test duration. Second, the standard scintigraphy egg meal was also of a smaller size than the oatmeal bar and ensure meal used previously for Gastric Alimetry reference interval development; however, these researchers felt this was an appropriate compromise because a sensitivity analysis has previously shown that smaller caloric intakes are sufficient to adequately profile gastric neuromuscular function with Gastric Alimetry. Third, these investigators included patients with BMI of 35 or higher in this study, while noting that data in this group should be interpreted with caution as per the Gastric Alimetry Guidelines. The main risk in high BMI patients is in over-estimating the low rhythm stability phenotype, due to declining signal-to-noise ratio; thus, the results were reassuring in that no patients with BMI of 35 or higher had this abnormality.
In an editorial on the afore-mentioned study by Wang et al (2024), Hasler (2024) stated that GA is also termed body surface gastric mapping; however, 2D surfaces are not generated during GA. Cutaneous signals reflect summation of 3 to 4 propagating waveforms with dispersal through subcutaneous tissues; therefore, cutaneous recording from any single electrode cannot accurately measure propagation of individual slow waves. These researchers previously characterized antegrade myoelectric propagation by means of cutaneous electrodes in healthy pigs, and others have detected myoelectric propagation in gastroparesis patients using a 25-electrode cutaneous system. Because GA has a 64-electrode array, it is anticipated that future reports delineating myoelectric propagation properties and documenting aberrant conduction in nauseated patients are forthcoming. This editorial queried whether GA is revolutionary. The system does represent an important advance over EGG by its ability to provide credible high-fidelity recordings with fewer artifacts, which these investigators postulated could aid in formulating treatment plans. The editorialist noted that although it can be argued whether these features constitute a revolution in diagnostic testing, this novel technology offers a reset for a long-stagnant field to address the still unanswered question as to what role gastric myoelectric dysfunction plays in the genesis of nausea and other symptoms.
Xu et al (2024) stated that adverse gastric symptoms persist in up to 20% of fundoplication operations completed for GERD, causing significant morbidity and driving the need for revisional procedures. Non-invasive techniques to examine the mechanisms of persistent post-operative symptoms are lacking. These investigators examined gastric myoelectrical abnormalities and symptoms in patients following fundoplication using a novel non-invasive body surface gastric mapping (BSGM) device. Patients with a previous fundoplication operation and ongoing significant gastro-duodenal symptoms and matched controls were included. BSGM using Gastric Alimetry was employed, consisting of a high-resolution 64-channel array, validated symptom-logging application, and wearable reader. A total of 16 patients with significant chronic symptoms following fundoplication were recruited, with 16 matched controls. Overall, 6 of 16 patients (37.5%) showed significant spectral abnormalities defined by unstable gastric myoelectrical activity (n = 2), abnormally high gastric frequencies (n = 3), or high gastric amplitudes (n = 1). Patients with spectral abnormalities had higher Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index scores than those of patients without spectral abnormalities (3.2 [range of 2.8 to 3.6] versus 2.3 [range of 2.2 to 2.8], respectively; p = 0.024). Moreover, 7 of 16 patients (43.8%) had BSGM test results suggestive of gut-brain axis contributions and without myoelectrical dysfunction. Increasing Principal Gastric Frequency Deviation and decreasing Rhythm Index scores were associated with symptom severity (r > 0.40; p < 0.05). The authors concluded that a significant number of patients with persistent post-fundoplication symptoms displayed abnormal gastric function on BSGM testing, which correlated with symptom severity. These researchers stated that these findings advanced the pathophysiologic understanding of post-fundoplication disorders, which may inform diagnosis and patient selection for medical therapy and revisional procedures.
Law et al (2024) noted that many diagnostic tests for gastro-duodenal symptoms, such as GES, GEBT, and EGG show variable intra-individual reproducibility over time. These investigators examined the short- and long-term reproducibility of BSGM in controls and patients with chronic gastro-duodenal disorders. Participants completed 3 standardized BSGM tests using Gastric Alimetry. The test encompassed a fasting baseline (30 mins), a 482-kCal standard meal, and a 4-hour post-prandial recording. The first 2 tests were more than 6 months apart and the last occurred approximately 1 week after the 2nd test, to evaluate long- and short-term reproducibility. A total of 14 patients with upper GI symptoms and 14 HCs were recruited. There were no significant differences in any BSGM metrics between the tests at short- and long-term (all p > 0.180). Lin's concordance correlation coefficients (CCC) for the primary metrics were high, ranging from 0.58 to 0.96, with intra-individual coefficients of variance (CVintra) ranging from 0.2% to 1.9%. Reproducibility was higher, and intra-individual variation lower, than in previous studies of GES (CCC = 0.54 to 0.83, CVintra = 3% to 77%), GEBT (CVintra = 8% to 11%), and EGG (CVintra = 3% to 78%). The authors concluded that BSGM spectral metrics showed high reproducibility and low intra-individual variation at both short- and long-term, with superior results to comparable tests. These researchers stated that the high reproducibility of Gastric Alimetry supported its role as a diagnostic aid for gastric dysfunction and a reliable tool for evaluating treatment outcomes and disease progression over time.
The authors stated that this study had several drawbacks. First, as there were multiple spectral phenotypes for patients with gastro-duodenal disorders, not all of these subgroups may have been adequately evaluated within the current sample, which may have under-estimated the true variability of the Gastric Alimetry metrics in certain groups. For example, only 1 patient had a low enough Gastric Alimetry Rhythm Index (GA-RI) score to be categorized as having low rhythm stability; thus, future research is needed to definitively examine the reproducibility of this phenotype over time. Second, although the tests were kept as standardized as possible to control for any variability, there was slight variation in the test timings and 3 subjects switched to alternative meals of equal caloric content. However, research has shown no significant differences in the results of EGG or BSGM for calorie-matched meals with different compositions. Third, these researchers did not account for menstrual cycle variability in pre-menopausal female subjects, with elevations in principal gastric frequency recently shown to occur during the luteal phase. These investigators stated that future research is needed to examine the effect of the menstrual cycle on the reproducibility of the Gastric Alimetry metrics. Nevertheless, despite slight variations in meal type and test timings, this study consistently showed high reproducibility of the Gastric Alimetry metrics, enhancing the ecological validity of these findings and underscoring the stability of these metrics over time. These investigators stated that future research, with larger sample sizes, could be carried out to further examine the reproducibility of the Gastric Alimetry metrics within individual patient groups. For example, further research could focus on different subgroupings of disorders of gut–brain interaction (DGBI), such as functional dyspepsia (FD), and chronic nausea and vomiting syndrome (CNVS), or within these subgroupings, such as examining the post-prandial distress syndrome and epigastric pain syndrome groupings within FD.
Hendry et al (2024) examined the effects of different frequencies of non-invasive median nerve stimulation (nMNS) on 2 autonomic responses: gastric slow waves under water-loading condition and heart rate variability (HRV). To the best of the authors’ knowledge, this was the 1st study to document the effects of different frequencies of nMNS on gastric slow waves (GSW) in humans under 5-min water-loading condition. A total of 12 healthy volunteers were fitted with a non-invasive BSGM, ECG, and a transcutaneous electrical nerve stimulation (TENS) device, and administered with 4 different nMNS frequencies (placebo-0 Hz, 40 Hz, 120 Hz, and 200 Hz) on 4 separate counter-balanced days. After the baseline and stimulation periods, a 5-min water-load test was carried out, and a post-water-load period was also recorded for ECG and GSW activity. Time-domain HRV parameters were analyzed with repeated-measures 1-way analysis of variance (ANOVA) and a post-hoc Tukey multiple comparison test. Parameters that failed normality tests underwent a Freidman test with a post-hoc Dunn multiple comparison test. GSW data were analyzed with repeated-measures mixed-effects ANOVA. In empty stomach (baseline versus stimulation), only the 40-Hz frequency statistically significantly (p = 0.0129) increased GSW amplitude in comparison with its own baseline. In full (distended) stomach, 40-Hz and 200-Hz stimulations showed a statistically significant difference (post-hoc multiple comparison adjusted, p = 0.0016 and p = 0.0183, respectively) in the Gastric Rhythm Index in comparison with the change obtained by placebo stimulation (baseline versus post-stimulation periods); 120-Hz nMNS showed a statistically significant difference (p = 0.0300) in the stress index in comparison with the decrease observed in the placebo group. However, 120-Hz nMNS did not induce a statistically significant change in gastric electrical activity compared to placebo stimulation. The nMNS did not follow the linear "dose-response" relationship between nMNS frequency and gastric/HRV parameters. The authors concluded that 40-Hz and 200-Hz nMNS frequencies showed the most promising results in response to gastric distension, in addition to 40 Hz for an empty stomach. These investigators stated that further research is needed to examine the potential therapeutic effects of these frequencies on gastric diseases such as gastroparesis, GERD, and FD that can be used in wrist wearables.
Mori (2024) stated that diabetic GI neuropathy is a diabetes-related complication, associated with a complex interplay of hyperglycemic damage, autoimmune responses, oxidative stress, GI hormones, as well as vascular insufficiency. Patients with diabetes should be monitored and therapeutic intervention introduced to prevent neuropathy due to diabetes before "the point of no return". The authors noted that determining gastric bioelectrical activity by body surface gastric mapping may be a promising option to monitor diabetic GI neuropathy. Available studies were limited to physiological assessment in mapping and to reporting the effects of loading with diet and drugs. In addition, BSGM faces several challenges that need to be overcome, such as anatomical variability, weak signal detection, noise and artifacts, reliance on complex algorithms, distinguishing gastric from colonic activity, as well as issues with electrode placement and skin contact. Moreover, the author stated that detailed pathophysiological assessment of diabetic gastroparesis will be possible in the near future.
Huang et al (2024) aimed to examine the effects of peripheral corticotropin-releasing hormone (CRH) infusion on gastric sensorimotor function, gastric electrical activity, and postprandial symptoms in healthy volunteers, as stress is known to influence gut-brain interactions but its mechanisms remain unclear. In a randomized, double-blind, placebo-controlled crossover design, 20 participants received either CRH or saline, followed by a washout period and crossover. Assessments included gastric emptying breath tests, body surface gastric mapping (BSGM) for myoelectrical activity and symptom profiling, salivary cortisol measurements, and gastric barostat studies for sensitivity and accommodation. Results showed that CRH significantly accelerated gastric emptying (mean half-time 65.2 vs. 78.8 min, P = 0.02), increased gastric amplitude during the first postprandial hour, and elevated salivary cortisol levels, while also heightening symptoms such as fullness and bloating. However, CRH did not alter gastric sensitivity to distention or accommodation compared to placebo. Limitations include the small sample size, use of a pharmacologic CRH dose whose physiological relevance is uncertain, potential variability in stress responses due to uncontrolled factors like anxiety or sleep, and the fact that findings in healthy subjects may not generalize to patients with chronic stress or gut-brain disorders.
Wang et al (2024) sought to assess the relationship between gastric remnant electrophysiological activity, gastrointestinal symptoms, and quality of life (QoL) in patients following gastric bypass surgery. The investigators recruited patients who had undergone gastric bypass or conversion-to-bypass procedures and utilized the Gastric Alimetry System, which includes a high-resolution electrode array and a validated symptom logging app, to record gastric activity. The protocol involved a 30-minute fasting baseline, a standardized meal stimulus, and four hours of post-prandial recordings. Symptoms and QoL were measured using validated questionnaires (PAGI-SYM and PAGI-QOL), and electrophysiological parameters such as frequency, BMI-adjusted amplitude, and the Gastric Alimetry Rhythm Index (GA-RI) were compared to reference intervals and matched controls. Results showed that one-third of patients experienced moderate to severe post-prandial symptoms and significantly reduced QoL compared to controls (median PAGI-SYM 28 ± 19 vs 9 ± 17, p < 0.01; PAGI-QOL 37 ± 31 vs 135 ± 22, p < 0.0001). Remnant gastric function was severely impaired, with undetectable frequencies in 84% of patients (vs 0% in controls) and markedly low GA-RI (0.18 ± 0.08 vs 0.51 ± 0.22, p < 0.0001; reference range > 0.25). Lower GA-RI and amplitude correlated with worse symptom and QoL scores. Study limitations include its observational design, modest sample size (38 participants), and inability to establish causality between remnant gastric dysfunction and symptoms/QoL. The findings suggest that disuse degeneration of the remnant stomach is common and associated with symptom burden and reduced QoL, but further research is needed to clarify causal mechanisms and potential interventions.
Huang et al (2024) aimed to evaluate how different meal sizes influence gastric bioelectrical activity measured by body surface gastric mapping (BSGM) in healthy individuals, with the goal of informing the use of BSGM in contexts where smaller meals may be required. Researchers pooled data from 238 healthy participants across multiple international cohorts, who underwent a standardized BSGM protocol involving a 30-minute fasting period followed by a 4-hour postprandial recording using the Gastric Alimetry system. Four test meals were compared: a standard 482 kcal meal (nutritional drink plus oatmeal bar) and three smaller meals of approximately 250 kcal (oatmeal bar alone, egg with toast, and pancake). Key metrics included BMI-adjusted amplitude, principal gastric frequency, Gastric Alimetry Rhythm Index (GA-RI), and Fed:Fasted Amplitude Ratio (ff-AR). All meals produced significant postprandial increases in amplitude and frequency during the first hour, but the larger standard meal elicited significantly higher amplitude and GA-RI compared to the oatmeal bar and egg meal, while differences with the pancake meal were not statistically significant, likely due to small sample size. No differences in frequency or ff-AR were observed across meals, and the three smaller meals showed comparable responses. Symptom burden was minimal overall, though the oatmeal bar group reported higher fullness and nausea scores than other meals. Limitations include the non-crossover design, potential group imbalances, and a small sample size for the pancake group, as well as movement artifacts during simultaneous breath testing, though these were mitigated by automated correction. The findings indicate that while lower-calorie meals can evoke expected postprandial physiological changes, they result in reduced amplitude and rhythm stability compared to the standard meal, highlighting the need for caution when interpreting BSGM results with variant meals and suggesting future work to establish adjusted normative reference ranges.
Varghese et al. (2025) aimed to develop and clinically evaluate a standardized, mechanism-based classification scheme for gastroduodenal disorders using the Gastric Alimetry system, which combines body surface gastric electrical mapping with validated symptom profiling. Conducted as a multicenter prospective cohort study, it enrolled 210 patients meeting Rome IV criteria for functional dyspepsia and chronic nausea and vomiting syndromes. Participants underwent a standardized Gastric Alimetry test involving fasting, a test meal, and four hours of postprandial recording, with concurrent symptom logging. Based on spectral analysis and symptom patterns, patients were categorized into three main groups: those with abnormal gastric electrical profiles, those with symptoms correlated to gastric activity, and those with symptoms independent of gastric activity. Results showed that 83% of patients could be phenotyped, with 38% exhibiting spectral abnormalities and others classified into symptom-based subgroups such as continuous, meal-induced, or sensorimotor patterns. Phenotypes demonstrated distinct associations with symptom severity, psychological factors, and quality of life; notably, amplitude-independent symptom profiles correlated strongly with depression and anxiety, while spectral abnormalities were linked to higher symptom burden but not psychological distress. Limitations included the relatively small size of some subgroups, incomplete characterization of certain patients, lack of gastric emptying data, and the need for further validation of rare phenotypes. Overall, the classification scheme offers a promising approach for guiding personalized management and is being applied in clinical and research settings.
Varghese et al. (2025) aimed to determine whether noninvasive body surface gastric mapping (BSGM) biomarkers, obtained using the Gastric Alimetry device, could predict symptomatic response to prokinetic therapy in patients with chronic gastroduodenal symptoms. The investigators prospectively recruited patients already taking oral prokinetic agents, regardless of their gastric emptying status, and performed BSGM after withholding prokinetics. The protocol included a 30-minute baseline, a standardized meal, and a 4-hour postprandial recording, followed by daily symptom diaries. A subset of patients starting prokinetics during the study was compared to matched controls not on prokinetics. Symptomatic response was defined using a minimum clinically important difference methodology. The study analyzed 42 patients (88% female, median age 36, median BMI 26) on prokinetics. Prescribing of prokinetics was not associated with BSGM metrics. Among patients already on prokinetics, lower BSGM amplitudes predicted reduced symptom burden, while low rhythm stability was associated with worse symptoms. In prokinetic-naive patients, a lower postprandial amplitude before starting therapy predicted symptomatic response (mean 37.5 ± 10.6 μV in responders vs. 54.8 ± 6.6 μV in non-responders, p = 0.047). The authors concluded that Gastric Alimetry biomarkers, particularly lower postprandial amplitude, may help identify patients most likely to benefit from prokinetic therapy, while impaired rhythm stability may predict poorer response. Limitations of the study include the small sample size, especially in the prokinetic-naive subgroup, and the observational design, which may introduce selection bias. Additionally, the study population was predominantly female and relatively young, which may limit generalizability. The findings require validation in larger, more diverse cohorts and in randomized controlled trials to confirm the predictive value of BSGM biomarkers for prokinetic response.
Varghese et al. (2025) sought to identify distinct subgroups within gastroparesis by using simultaneous body surface gastric mapping (BSGM) and gastric emptying breath testing (GEBT) in patients with chronic gastroduodenal symptoms and negative gastroscopy. Patients underwent a 30-minute fasting baseline and a 4-hour postprandial recording, during which both BSGM and GEBT were performed. The BSGM "meal response ratio" (MRR) was used to compare gastric amplitude in the first two hours after a meal to the subsequent two hours, with a lagged meal response defined as MRR ≤ 1. Among 143 patients (79% female, median age 31), 25.2% had delayed gastric emptying. Those with a lagged meal response on BSGM had significantly longer gastric emptying half-times (T1/2) and a higher prevalence of delayed emptying compared to those without a lagged response. In patients with delayed emptying, BSGM identified several phenotypes: lagged meal response (25%), low amplitude/rhythm stability (30.6%), elevated gastric frequencies (11.1%), and normal spectral analysis (33.3%). There was only a weak correlation between T1/2 and total symptom burden. The study concluded that combining BSGM and GEBT can define clinically relevant subgroups of gastroparesis, including a novel group characterized by delayed postprandial onset of gastric motor activity associated with delayed emptying. Limitations include the observational design, potential selection bias, and a predominantly young, female cohort, which may limit generalizability. The weak correlation between gastric emptying rates and symptom burden also highlights the complexity of gastroparesis pathophysiology and the need for further validation of these subgroups in larger, more diverse populations.
Humphrey et al. (2025) evaluated body surface gastric mapping (BSGM) as a noninvasive tool to improve diagnosis and management of pediatric disorders of gut-brain interaction (DGBI). The authors explained that BSGM uses a high-density electrode array to record gastric slow-wave activity with simultaneous symptom logging, enabling objective phenotyping of neuromuscular dysfunction, delayed meal responses, and symptom profiles. The authors stated that early pediatric data show BSGM is feasible, safe, and reproducible, with phenotypes that correlate with symptoms and quality of life and align with antroduodenal manometry. Limitations include limited pediatric-specific reference ranges, small sample sizes, and lack of longitudinal outcome data; larger, multicenter studies are needed to validate clinical utility and guide individualized care. The study aimed to assess BSGM's utility in pediatric DGBI by evaluating its feasibility, safety, and ability to identify distinct gastric phenotypes that correlate with symptoms and guide management. The study utilized BSGM technology, comprised of a high-density, flexible 64-electrode array that captures gastric slow-wave activity with validated artifact rejection and BMI-adjusted metrics. The protocol involved a standardized 4.5-hour test with fasting baseline, standardized meal, and postprandial recording, with real-time symptom logging using validated pediatric pictograms. Participants included adolescents aged 12–21 years with functional dyspepsia or gastroparesis, plus healthy controls. Study outcomes include gastric frequency, rhythm stability, amplitude, and meal response; symptom severity and quality of life; and concordance with antroduodenal manometry. The investigators reported that BSGM was well tolerated and safe in adolescents, with reproducible metrics over 1 week and 6 months. Three distinct BSGM phenotypes were identified – normal, delayed meal response, and dysrhythmic – with clinically meaningful differences in symptoms, physical health, and anxiety. The investigators stated that BSGM dysrhythmic patterns aligned with neuropathic findings on antroduodenal manometry and correlated with higher nausea and bloating. The investigators reported that BSGM phenotypes helped differentiate patients with overlapping symptoms and may guide targeted therapy. Study limitations include limited pediatric-specific reference ranges, as adult norms are used provisionally and pediatric-specific ranges are needed. Sample sizes were small, limiting generalizability and subgroup analysis. Longitudinal outcome data are lacking, so the impact of BSGM-guided care on symptoms and quality of life remains uncertain. Broader validation is needed across diverse pediatric populations and clinical settings. The investigators concluded that BSGM is a promising, noninvasive tool for pediatric DGBI, providing objective gastric phenotypes that correlate with symptoms and align with invasive tests. Larger, longitudinal studies are needed to establish pediatric norms and confirm clinical utility.
Lim et al. (2025) sought to determine whether hormonal contraception influences nausea and gastric myoelectrical activity in women with chronic gastroduodenal disorders. The investigators recruited premenopausal women with chronic gastroduodenal symptoms, comparing those using hormonal contraception to those not using it. Gastric myoelectrical activity was assessed using body surface gastric mapping, and symptom severity, particularly nausea, was measured using validated patient-reported outcome tools. The results demonstrated that women on hormonal contraception experienced less severe nausea and more stable gastric myoelectrical activity compared to those not on contraception, who showed greater symptom fluctuation and more frequent gastric dysrhythmias. These findings suggest that hormonal contraception may stabilize gastric myoelectrical rhythms and reduce symptom variability, possibly by modulating the effects of endogenous sex hormones on gastric motility and sensorimotor function. However, the study has several limitations. The sample size was modest, which may limit generalizability. The observational design precludes definitive conclusions about causality. Hormonal contraception types and dosages were heterogeneous, and the study did not control for all potential confounders, such as diet, stress, or other medications. Additionally, the assessment of gastric myoelectrical activity, while advanced, remains an indirect measure of gastric motility and may not fully capture the complexity of underlying pathophysiology. The authors concluded, however, that, despite these limitations, the study provides important insights into the role of sex hormones and hormonal contraception in modulating symptoms and gastric electrophysiology in women with chronic gastroduodenal disorders.
Sadaka et al. (2025) aimed to determine whether non-invasive body surface gastric mapping (BSGM) can reliably diagnose neuropathic gastroduodenal disorders in children, compared to the gold standard of antroduodenal manometry (ADM). The researchers enrolled 15 pediatric subjects (mostly female, ages 10–19) who underwent clinically indicated ADM using high-resolution water-perfused catheters, with simultaneous BSGM recordings. Real-time symptoms were logged at 15-minute intervals, and nausea severity was quantified. The protocol included fasting, provocative testing, a meal, and postprandial monitoring. ADM results were categorized as neuropathy, myopathy, post-prandial hypomotility, or normal, while BSGM metrics included principal gastric frequency, BMI-adjusted amplitude, and rhythm index. The investigators reported that BSGM dysrhythmia perfectly matched ADM-diagnosed neuropathy, with patients in this group exhibiting significantly lower rhythm stability and higher nausea and bloating scores than others. Normal ADM findings were consistent with normal BSGM in 83.3% of cases. Notably, delayed gastric emptying did not correlate with neuropathic findings. The authors concluded that BSGM reliably identifies gastrointestinal neuropathy with results identical to ADM and correlates with symptom severity, suggesting BSGM could serve as an actionable biomarker when ADM is not feasible. Limitations of the study include the small sample size (n=15), single-center design, and pediatric population, which may limit generalizability. Additionally, the study did not address long-term outcomes or the utility of BSGM in broader clinical settings, and the lack of correlation with gastric emptying highlights the complexity of gastroduodenal disorders and the need for multimodal assessment.
Humphrey et al. (2025) investigated whether body surface gastric mapping (BSGM) can delineate specific patient phenotypes in adolescents with functional dyspepsia (FD) and gastroparesis, conditions that often present with overlapping symptoms and pose diagnostic challenges. In a prospective cross-sectional design, 56 adolescents (31 controls and 25 patients, median age 16, 96% female) underwent standardized BSGM, with simultaneous symptom reporting and validated questionnaires assessing physical health and psychometrics. The study found that adult BSGM reference intervals were applicable to adolescents. Importantly, three distinct BSGM phenotypes emerged among patients: BSGM Normal, BSGM Delay, and Low Stability/Low Amplitude, each showing significant differences in spectral metrics (BMI-adjusted amplitude and Gastric Alimetry Rhythm Index) and correlating with variations in nausea, physical health, and anxiety scores. Despite similar clinical profiles between FD and gastroparesis patients, BSGM phenotyping revealed clinically meaningful distinctions that may guide individualized therapy. Limitations include the modest sample size, predominance of female subjects, and recruitment from only two centers, which may affect generalizability. The cross-sectional nature precludes assessment of longitudinal outcomes or treatment response. Additionally, while BSGM identified phenotypes with symptom correlations, its direct impact on clinical management and long-term utility remains to be established.
Wang et al (2025) aimed to investigate the long-term effects of laparoscopic sleeve gastrectomy on gastric electrophysiology and its association with persistent gastrointestinal symptoms and quality of life using a non-invasive body surface gastric mapping technique (Gastric Alimetry). The researchers recruited 38 post-sleeve gastrectomy patients and 38 matched healthy controls. Participants underwent 30-minute fasting and 4-hour postprandial recordings, and key metrics such as Principal Gastric Frequency, BMI-adjusted amplitude, Gastric Alimetry Rhythm Index, and fed-to-fasted amplitude ratio were analyzed against normative ranges. Symptom burden and quality of life were assessed using validated questionnaires. Results showed that 35 of 38 patients exhibited at least one abnormal gastric parameter, most commonly reduced frequency (mean 2.3 vs 3.08 cpm in controls, p<0.001) and amplitude (14.8 vs 31.5 µV, p<0.001). Patients reported significantly higher symptom scores and poorer quality of life compared to controls (PAGI-SYM 20 vs 7; PAGI-QOL 27 vs 136; both p<0.001). Correlation analyses revealed that higher amplitude and rhythm stability were associated with bloating, while lower amplitude correlated with heartburn and greater weight loss. The study concluded that sleeve gastrectomy leads to consistent reductions in gastric pacemaker frequency and amplitude, with these changes linked to postoperative symptoms. Limitations include the smaller meal size for patients compared to controls, potential selection bias toward symptomatic individuals, and minor demographic differences between groups, although BMI adjustments and normative reference ranges were used to mitigate these factors.
A randomized, prospective pilot study by Abraham et al (2025) aimed to assess whether combining gastric emptying scintigraphy (GES), the current reference standard for diagnosing gastroparesis, with body surface gastric mapping (BSGM) using Gastric Alimetry improves diagnostic accuracy and management certainty in patients with chronic gastroduodenal symptoms. Sixteen adults referred for GES underwent both tests, and two motility specialists sequentially reviewed results to formulate and revise management plans. The primary endpoint was the change in clinical decisions after incorporating both test results, alongside clinician-perceived certainty ratings. Results showed that combined testing significantly increased diagnostic precision: definitive diagnoses rose from 12.5% at baseline to 50% after reviewing both tests, and management certainty improved markedly (p<0.05). While GES and BSGM detected largely non-overlapping abnormalities, BSGM provided additional phenotypic insights even in patients with normal results. Both tests were rated as equally contributory to clinical decision-making, and combined results led to substantial management changes in over 60% of cases, including medication adjustments, dietary recommendations, and psychological interventions. Limitations include the small sample size, single-center design, potential clinician bias, and lack of outcome data on whether management changes improved patient symptoms or reduced healthcare utilization. Additionally, clinician utility questionnaires were not formally validated for this cohort. Overall, the study suggests that integrating BSGM with GES enhances diagnostic confidence and supports more tailored interventions for suspected gastroparesis, warranting larger multicenter trials to confirm these findings.
Law et al (2025) sought to develop and validate the Alimetry Gut-Brain Wellbeing Survey–Youth Version (AGBW-Y), a mental health assessment tool tailored for adolescents aged 12–17 years with chronic gastroduodenal symptoms. Recognizing the lack of age-appropriate instruments for this population, researchers employed a multi-phase, co-design approach involving clinicians and young people. In Phase 1, feedback from 19 pediatric clinicians and 33 adolescents guided adaptations to the adult version of the survey, including simplifying language and removing reverse-coded items to improve clarity and usability. Phase 2 involved psychometric validation using an anonymous online survey completed by 128 adolescents meeting Rome IV criteria for gastroduodenal disorders. The final scale comprised a patient preface, 10 closed-ended items assessing depression, stress, and anxiety, and an optional open-ended question. Results demonstrated excellent internal consistency (α = .91 for the total scale; .75–.85 for subscales) and strong evidence of convergent, divergent, and concurrent validity, with large effect sizes across multiple validated mental health measures. Participants rated the tool as easy to complete and understand, and qualitative feedback highlighted its relevance and accessibility. Limitations include a predominantly female, white, and Western sample, potential recruitment bias, and the cross-sectional design, which precluded assessment of predictive validity or responsiveness to change. Additionally, the survey is currently available only in English, and future research should explore its applicability across diverse cultural contexts and longitudinal outcomes.
Simmonds et al (2025) aimed to determine how vomiting affects body surface gastric mapping (BSGM) results, a non-invasive test used to assess gastric myoelectrical activity and guide diagnosis of gastroduodenal disorders. Researchers analyzed a large database of 2,595 de-identified BSGM tests, identifying 49 vomiting events for qualitative review and 32 for quantitative analysis, excluding cases with pre-meal vomiting, multiple episodes, or significant artifacts. Standardized test protocols included a baseline recording, a fixed-calorie meal, and a 4-hour postprandial recording. BSGM metrics such as Gastric Alimetry Rhythm Index (GA-RI) and BMI-adjusted amplitude were examined in six 5-minute epochs surrounding vomiting events using mixed-effects models. Results showed that vomiting generally had minimal impact on overall test interpretation, with 90% of cases maintaining consistent spectral profiles. Transient decreases in GA-RI were observed within 5 minutes before and after vomiting (−0.27 and −0.21, respectively; p < 0.05), while BMI-adjusted amplitude changes were not statistically significant. In rare cases (8%), vomiting led to prolonged low amplitude or delayed meal responses, but these normalized within 1.5 hours. Symptom analysis revealed significant reductions in nausea, bloating, and excessive fullness following vomiting. Limitations include the retrospective design, lack of linkage to medical histories, inability to confirm vomiting volume or event validity, and exclusion of patients on motility-altering medications. Overall, vomiting caused brief, localized changes without compromising the integrity of BSGM tests, suggesting this method remains reliable for evaluating patients with vomiting symptoms, unlike gastric emptying studies that are invalidated by emesis.
Varghese et al (2025) aimed to clarify the role of autonomic dysfunction in chronic gastroduodenal disorders and its relationship to gastric physiology and symptoms, hypothesizing that multimodal testing would reveal distinct mechanistic subgroups. In a prospective observational cohort of 80 adults with chronic gastroduodenal symptoms, participants underwent expert autonomic evaluation, gastric emptying scintigraphy, and body surface gastric mapping (BSGM) using Gastric Alimetry. Gastroparesis was diagnosed in 33.8% of patients, autonomic dysfunction in 26.3%, and abnormal BSGM in 25%. Both autonomic dysfunction and abnormal BSGM were more common in gastroparesis, but rarely co-occurred, suggesting distinct pathophysiological mechanisms. Autonomic dysfunction independently predicted delayed gastric emptying (OR 13.8, p<0.001) and was associated with an earlier postprandial motor response and greater symptom burden, particularly excessive fullness and early satiation, even when BSGM was normal. Conversely, abnormal BSGM phenotypes, such as high gastric frequencies, were strongly associated with gastroparesis but not autonomic impairment. These findings indicate that autonomic dysfunction and gastric myoelectrical abnormalities represent separate contributors to gastroduodenal pathophysiology. Limitations include incomplete formal autonomic testing for all participants, potential referral bias, and limited power to analyze specific autonomic metrics. Overall, the study underscores the value of comprehensive multimodal physiological profiling to subtype patients and guide personalized management beyond conventional gastric emptying tests.
Xu et al (2025) aimed to investigate whether gastric myoelectrical abnormalities, measured using body surface gastric mapping (BSGM) with Gastric Alimetry®, are associated with gastroesophageal reflux disease (GERD) severity and reflux events detected by 24-hour pH monitoring. Forty adults were enrolled, including 20 patients undergoing pH testing for suspected GERD (12 confirmed GERD, 8 symptomatic non-GERD) and 20 healthy controls. Participants underwent a standardized 4.5-hour BSGM test with symptom logging during the pH monitoring period. Gastric rhythm stability was quantified using the Gastric Alimetry Rhythm Index (GA-RI), and correlations were assessed between GA-RI, reflux burden, and symptoms, including temporal analyses in 15-minute epochs. Results showed that GERD patients had significantly lower GA-RI values than controls, indicating reduced gastric rhythm stability, and GA-RI was negatively correlated with overall acid exposure (DeMeester score, r = -0.46, p = 0.042). However, no temporal association was found between rhythm instability and reflux episodes or heartburn severity. Instead, transient decreases in GA-RI were temporally linked to nausea and excessive fullness. Only 10% of patients exhibited major dysrhythmic phenotypes, suggesting that severe neuromuscular abnormalities are uncommon in GERD. Study limitations include a modest sample size, heterogeneous patient selection, potential confounding from proton pump inhibitor use, and differences in pH monitoring devices across centers. Additionally, the presence of esophageal catheters may have influenced gastric physiology, and the observational design limits causal inference. Overall, the findings suggest that gastric rhythm instability is associated with greater reflux burden and symptom severity but does not directly trigger reflux events, positioning GA-RI as a potential biomarker for gastric dysfunction in GERD.
Law et al (2025) aimed to explore how psychological factors such as depression, anxiety, and stress relate to specific physiological phenotypes in patients with chronic gastroduodenal symptoms, using body surface gastric mapping (BSGM). Researchers conducted a cross-sectional analysis of 278 patients meeting Rome IV criteria for functional dyspepsia or chronic nausea and vomiting syndrome. Participants underwent standardized BSGM testing with Gastric Alimetry, which included a fasting baseline, a standardized meal, and a four-hour postprandial recording. Concurrently, validated psychometric assessments and symptom tracking were performed. Patients were classified into phenotypes based on BSGM spectral metrics and symptom patterns. Results showed high prevalence of psychological comorbidities, with 45% reporting depression and 46% anxiety. While overall symptom severity correlated with worse mental health, these associations varied by phenotype. Abnormal rhythm stability predicted higher depression and stress, whereas patients with normal spectral metrics but continuous or sensorimotor symptom profiles exhibited the strongest associations with depression, anxiety, stress, and reduced quality of life. Other symptom patterns showed weaker or no associations. The study concludes that psychological burden is not uniform but phenotype-specific, suggesting that patients with normal gastric rhythms and persistent symptoms may benefit most from integrated psychological interventions. Limitations include its observational design, which precludes causal inference, limited global generalizability due to Western-centric sampling, and underrepresentation of less common phenotypes, which may affect subgroup analyses.
Ayubi et al (2025) aimed to determine whether body surface gastric mapping (BSGM) phenotypes could predict symptomatic response to gastric peroral endoscopic myotomy (GPOEM) in patients with refractory gastroparesis. Thirty patients were recruited at King’s College Hospital between November 2022 and July 2025 and underwent BSGM using Gastric Alimetry® prior to GPOEM. The protocol included fasting and postprandial recordings after a standardized meal, and phenotypes were classified based on rhythm stability, gastric frequency, meal response, symptom correlation, and continuous symptom burden. Treatment success was defined as at least a one-point reduction in the Gastroparesis Cardinal Symptom Index or complete symptom resolution at follow-up. Results showed that 53% of patients responded to GPOEM, with all individuals exhibiting dysrhythmic or continuous phenotypes achieving success, while those with high gastric frequency consistently failed. Higher principal gastric frequency was significantly associated with non-response (p=0.03), and overall symptom scores improved post-procedure (p<0.001). Limitations include the small sample size, single-center design, evolving classification schemes for BSGM phenotypes, and relatively short median follow-up of seven months. Further validation through larger, multicenter studies is needed to confirm these findings and refine patient selection strategies.
Gharibans et al (2026) aimed to develop and validate a set of digital symptom scores for gastroduodenal disorders that align with Rome IV criteria, using a standardized, real-time assessment during a Gastric Alimetry test. This noninvasive test combines body surface gastric mapping with an app-based platform for symptom logging over a 4.5-hour period following a standardized meal. A cohort of 109 adults meeting Rome IV criteria for functional dyspepsia (FD) and/or chronic nausea and vomiting syndrome (CNVS) was recruited, and participants recorded symptoms such as nausea, pain, bloating, and reflux using validated pictograms and Likert scales. Four composite symptom scores were created to represent nausea/vomiting, postprandial distress, epigastric pain, and burning/reflux. Statistical analyses, including pairwise t-tests and logistic regression, demonstrated strong alignment between these scores and Rome IV categories, with good discrimination for CNVS (AUC = 0.85) and EPS (AUC = 0.80), and moderate discrimination for PDS (AUC = 0.68). Usability testing with clinicians confirmed the scores’ acceptability and clinical utility, noting their ability to streamline symptom profiling and support diagnostic decisions. Limitations include the single-country cohort and lack of validation in diverse populations, though the authors suggest generalizability given the global consistency of Rome IV classifications. The authors concluded that, overall, the study introduces a practical, user-friendly diagnostic tool that may improve symptom assessment and complement physiological testing in gastroduodenal disorders.
Colonic Motility Studies
Dinning and colleagues (2016) noted that the past few years have seen an increase in the number of research and clinical groups around the world using high-resolution manometry (HRM) to record contractile activity in the ano-rectum and colon. Yet despite the uptake and growing number of publications, the clinical utility and potential advantages over traditional manometry remain undetermined. Nearly all of the publications in the field of anorectal and colonic HRM have been published within the last 3 years. These studies have included some data on normal ranges in healthy adults, and abnormalities in patient groups with constipation or fecal incontinence, anal fissure, perineal descent, rectal cancer, and Hirschsprung's disease. Most of the studies have been conducted on adults, with only 3 published studies in pediatric populations. Very few studies had attempted to show advantages of HRM over traditional manometry The authors concluded that high-resolution anorectal and colonic manometry provided a more comprehensive characterization of motility patterns and coordinated activity; this may help to improve the understanding of the normal physiology and pathophysiology in these regions. To-date, however, no published study has conclusively demonstrated a clinical, diagnostic, or interventional advantage over conventional manometry.
Jaung and colleagues (2017) stated that abnormal colonic pressure profiles and high intra-luminal pressures are postulated to contribute to the formation of sigmoid colon diverticulosis and the pathophysiology of diverticular disease. These investigators reviewed the evidence for abnormal colonic pressure profiles in diverticulosis. All published studies investigating colonic pressure in patients with diverticulosis were searched in 3 databases (Medline, Embase, Scopus). No language restrictions were applied. Any manometry studies in which patients with diverticulosis were compared with controls were included. The Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies was used as a measure of risk of bias. A cut-off of five or more points on the NOS (fair quality in terms of risk of bias) was chosen for inclusion in the meta-analysis. A total of 10 studies (published 1962 to 2005) met the inclusion criteria. The studies followed a wide variety of protocols and all used low-resolution manometry (sensor spacing range 7.5 to 15 cm); 6 studies compared intra-sigmoid pressure, with 5 of 6 showing higher pressure in diverticulosis versus controls, but only 2 reached statistical significance. A meta-analysis was not performed as only 2 studies were above the cut-off and these did not have comparable outcomes. The authors concluded that this systematic review of manometry data showed that the evidence for abnormal pressure in the sigmoid colon in patients with diverticulosis is weak. Existing studies utilized inconsistent methodology, showed heterogeneous results and were of limited quality. They stated that higher quality studies using modern manometric techniques and standardized reporting methods are needed to clarify the role of colonic pressure in diverticulosis.
Arbizu and co-workers (2017) evaluated the change in colon manometry (CM) parameters and interpretation comparing results when the study was performed the same day after the motility catheter was placed under anesthesia or the following day. CM catheter was placed with colonoscopy under anesthesia and recorded on day 1 and repeated on day 2. Study parameters including motility index during fasting, post-prandial and post-Bisacodyl challenge phase; gastro-colonic response; number, presence and propagation of high amplitude propagating contractions (HAPCs); and, study interpretation were compared between both the days. Motility index (fasting, post-Bisacodyl phase, p < 0.05), HAPC number (10.1 versus 6.6, p = 0.01) and the proportion of patients having HAPCs (92% versus 70%, p = 0.002) was significantly higher on day 2 versus day 1. HAPC propagation improved on day 2 versus day 1 (fully propagated, 49% versus 37%; partially propagated, 43% versus 33%; absent 8% versus 30%). Study interpretation changed from day 1 to day 2. On day 1, 37% had a normal study and 63% had an abnormal study. On day 2, all patients with a normal study on day 1 remained normal, and patients with an abnormal study on day 1, 53% remained abnormal and 47% had a normal study. The authors concluded that CM parameters were affected the day the catheter was placed with colonoscopy under anesthesia. The number, presence, and propagation of HAPCs were significantly higher/improved on day 2 compared to day 1. Overall, CM interpretation changed from abnormal to normal from day 1 to day 2 in 47% of the patients.
Tanaka and associates (2018) noted that the prevalence and severity of irritable bowel syndrome (IBS) declines with age, but the cause of this is unknown. In a prospective study, these researchers tested 2 hypotheses: First, autonomic nervous system (ANS) responses to eating and bowel distention, measured by heart rate variability (HRV), differs by age in IBS patients. Second, HRV is correlated with colonic motility and IBS symptoms. A total of 156 Rome III positive IBS patients and 31 healthy controls underwent colonic manometry with bag distention in the descending colon, followed by ingestion of an 810-kcal meal. HRV, evaluated by low frequency (%LF; 0.04 to 0.15 Hz) component, high frequency (%HF; 0.15 to 0.40 Hz) component, and the LF/HF ratio, was measured during colonic distention and after the meal. Motility index and subjective symptom scores were simultaneously quantified. Both colonic distention and eating decreased%HF and increased the LF/HF ratio, and both indices of ANS correlated with age. In IBS patients,%HF negatively correlated with the post-prandial motility index after adjusting for age. The%HF and LF/HF ratios also correlated with psychological symptoms but not bowel symptoms in IBS patients. The authors concluded that these findings suggested that, decreased vagal activity is associated with increase in age and greater post-prandial colonic motility in patients with IBS, which may contribute to post-prandial symptoms.
The authors stated that this study had several limitations. First, blood glucose and lipid levels were not monitored when assessing the response to eating. These changes in metabolism may affect colonic motility, vascular regulation, or emotional state. Total meal calories may also affect colonic motility, but variations in calories consumed were unlikely to contribute to error variance in this study because subjects consumed a standard high-fat meal. Second, the number of male subjects was too small to test for sex differences. A previous study reported sex differences in ANS in IBS patients. However, the findings of this study suggested that age may have a greater impact on HRV than does sex. Third, as the post-hoc analyses, these investigators set 37 years to divide the young and old age groups based on the ratio of LF/HF changes by age, which might be biased. However, misleading conclusions appeared to be unlikely since the post-prandial motor activity significantly correlated with the post-prandial%HF even in all IBS patients. A study previously proposed that QT and RR variability may be different among young (20 to 35 years), middle-aged (40 to 55 years), and elderly (above 60 years) subjects. They stated that further validation studies are needed to confirm the cut-off point by age on autonomic nervous function in patients with IBS.
Colonic Motility Studies / Colonic Manometry to Guide Decision-Making for Surgery in Children with Refractory Colonic Motility / Defecatory Disorders
Rao and associates (2004) stated that the colonic neuromuscular dysfunction in patients with constipation and the role of colonic manometry is incompletely understood. These researchers studied prolonged colonic motility and evaluated its clinical significance; 24-hour ambulatory colonic manometry was performed in 21 patients with slow-transit constipation and 20 healthy controls by placing a 6-sensor solid-state probe up to the hepatic flexure. Quantitative and qualitative manometric analysis was performed in 8-hour epochs; subjects were followed-up for 1 year. Constipated patients showed fewer pressure waves and lower area under the curve (AUC) (p < 0.05) than controls during daytime, but not at night. Colonic motility induced by waking or meal was decreased (p < 0.05) in patients. High-amplitude propagating contractions (HAPCs) occurred in 43% of patients compared to 100% of controls and with lower incidence (1.7 versus 10.1, p < 0.001) and propagation velocity (p < 0.04). Manometric features suggestive of colonic neuropathy were observed in 10, myopathy in 5, and normal profiles in 4 patients; 7 patients with colonic neuropathy underwent colectomy with improvement. The remaining patients were managed conservatively with 50% improvement at 1 year. The authors concluded that patients with slow-transit constipation exhibited either normal or decreased pressure activity with manometric features suggestive of colonic neuropathy or myopathy as evidenced by absent HAPC or attenuated colonic responses to meals and waking. These researchers stated that in refractory patients, colonic manometry may be useful in characterizing the underlying pathophysiology and in guiding therapy.
Brown and colleagues (2005) noted that patients with rectal prolapse have abnormal hind-gut motility. These investigators examined the effect of rectal prolapse surgery on colonic motility. A total of 12 patients undergoing sutured rectopexy were studied before and 6 months after surgery by colonic manometry, colonic transit study and clinical assessment of bowel function. The results were compared with those from 7 control subjects. Before surgery, colonic pressure was greater in patients than controls (p < 0.050); controls responded to a meal stimulus by increasing colonic pressure; this increase was absent in patients. After rectopexy, colonic pressure reduced towards control values and patients' colonic pressure response to a meal returned; HAPCs were observed in all controls, but in only 3 patients before and 2 patients after surgery; 3 patients had prolonged colonic transit before and 8 after rectopexy. The authors concluded that patients with rectal prolapse have abnormal colonic motility associated with reduced HAPC activity. Rectopexy reduced colonic pressure; but failed to restore HAPCs, reduce constipation or improve colonic transit.
van den Berg and co-workers (2006) defined the predictive value of colonic manometry and contrast enema before cecostomy placement in children with defecation disorders. Medical records, contrast enema, and colonic manometry studies were reviewed for 32 children with defecation disorders who underwent cecostomy placement between 1999 and 2004. Diagnoses included idiopathic constipation (n = 13), Hirschsprung's disease (n = 2), cerebral palsy (n = 1), imperforate anus (n = 6), spinal abnormality (n = 6), and anal with spinal abnormality (n = 4). Contrast enemas were evaluated for the presence of anatomic abnormalities and the degree of colonic dilatation. Colonic manometry was considered normal when HAPCs occurred from proximal to distal colon. Clinical success was defined as normal defecation frequency with no or occasional fecal incontinence (FI). Colonic manometry was carried out on 32 and contrast enema on 24 patients before cecostomy. At follow-up, 25 patients (78%) fulfilled the success criteria. Absence of HAPCs throughout the colon was related to unsuccessful outcome (p = 0.03). Colonic response with normal HAPCs after bisacodyl administration was predictive of success (p = 0.03). Presence of colonic dilatation was not associated with colonic dysmotility. The authors concluded that colonic manometry was helpful in predicting the outcome after cecostomy. Patients with generalized colonic dysmotility were less likely to benefit from use of antegrade enemas via cecostomy. Normal colonic response to bisacodyl predicted favorable outcome.
Mugie and colleagues (2013) noted that in adults, colonic manometry and colonic scintigraphy are both valuable studies in discriminating normal and abnormal colonic motility. These researchers compared the diagnostic yield and tolerability of colonic manometry and colonic scintigraphy in children with severe constipation. A total of 26 children (mean age of 11.4 years, 77% boys) who had received colonic manometry and colonic scintigraphy as part of a colonic motility evaluation were included. Manometry was performed as per department protocol. After swallowing a methacrylate-coated capsule containing indium-111, images were taken at 4, 24, and 48 hours, and geometric centers were calculated. Results of both tests were categorized in 3 groups: normal, abnormal function in the distal part of the colon, and colonic inertia. Cohen κ was used for the level of agreement. Patients and parents completed a questionnaire regarding their experience. Colonic scintigraphy showed normal transit time in 20%, delay in the distal colon in 48%, and colonic inertia in 32% of patients. Colonic manometry was normal in 40%, abnormal in the distal colon in 40%, and colonic inertia was diagnosed in 20%; the κ score was 0.34. All 5 patients with colonic inertia during manometry had a similar result by scintigraphy; 88% of patients preferred scintigraphy over manometry and 28% of parents preferred colonic manometry over scintigraphy. The authors concluded that colonic manometry and colonic scintigraphy had a fair agreement regarding the categorization of constipation; scintigraphy was well-tolerated in pediatric patients and may be a useful tool in the evaluation of children with severe constipation.
Liem and associates (2014) stated that colonic manometry is used in evaluating children with defecation disorders unresponsive to conventional treatment. The most commonly reported protocol in pediatrics consists of a study that lasts approximately 4 hours. Given the wide physiological variations in colonic motility throughout the day, longer observation may detect clinically relevant information. These researchers compared prolonged colonic manometry studies in children referred for colonic manometry with the more traditional short water-perfused technology. Colonic manometry studies of 19 children (8 boys, mean age of 9.4 ± 0.9, range of 3.9 to 16.3) with severe defecation disorders were analyzed. First, a "standard test" was performed with at least 1-hour fasting, 1-hour post-prandial, and 1-hour post-bisacodyl provocation recording. Afterwards, recordings continued until the next day. In 2 of the 19 children, prolonged recording provided extra information. In 1 patient with functional non-retentive FI who demonstrated no abnormalities in the short recording, 2 long clusters of HAPCs were noted in the prolonged study, possibly contributing to the FI. In another patient evaluated after failing use of antegrade enemas through a cecostomy, short recordings showed colonic activity only in the most proximal part of the colon, whereas the prolonged study showed normal motility over a larger portion of the colon. The authors concluded that prolonged colonic measurement provided more information regarding colonic motor function and allowed detection of motor events missed by the standard shorter manometry study.
El-Chammas and colleagues (2014) noted that colon manometry is usually performed using the 8-pressure sensor water-perfused manometry system. High-resolution manometry (HRM), using closely spaced solid-state pressure recording sensors, provided more detailed information of gut luminal pressure changes, and, by displaying the HRM data as a pressure topography plot (PTP), helps with data interpretation. These investigators compared the colon and rectal luminal pressure data obtained using 8 pressure sensors and displayed as conventional line plot (CLP) with data obtained using a custom-made solid state manometry catheter with 36 pressure recording sensors and displayed as PTP. They evaluated colon manometry patterns during fasting, response to meal, and bisacodyl stimulation in 10 patients with constipation and stool expulsion disorders. Data from 8 pressure sensors were displayed as CLP and data from 36 pressure sensors as PTP; 2 gastroenterologists independently interpreted these studies. They calculated variability in interpreting colon, rectal, and anal manometry data. Inter-mode, inter-observer, and intra-observer reliability were good-to-excellent for recognizing colon contraction patterns when data were displayed as PTP compared with when displayed as CLP, whereas the reliability for recognizing anal contractions were poor-to-excellent. The authors concluded that colonic and anal manometry patterns were easily recognized when HRM data were expressed as PTP. Obtaining information of colonic luminal pressure changes with rectum and anal pressure changes using HRM could aid in better understanding the pathophysiology of pediatric constipation and stool expulsion disorders.
Rodriguez and associates (2017) stated that over the last few years, the study of the colon and anorectal function has experienced great technical advances that have facilitated the performance of the tests and have allowed a more detailed characterization of reflexes and motor patterns. As a result, researchers have achieved a much better understanding of the pathophysiology of children with defecation problems. Anorectal and colonic manometry are now commonly used in all major pediatric referral centers as diagnostic tools and to guide the management of children with intractable constipation and fecal incontinence, especially when a surgical intervention is being considered. The authors highlighted some of the recent advances in pediatric colon and anorectal motility testing including indications and preparation for the studies, and how to perform and interpret the tests. This update has been endorsed by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).
Surjanhata and co-workers (2018) noted that chronic constipation may be categorized as normal transit (NTC), slow transit (STC), or outlet obstruction. Colonic wake response is a relative increase in colonic motility upon awakening. Colonic manometry studies have demonstrated attenuated wake response in STC. These researchers evaluated wake response among healthy (H), NTC, and STC patients using wireless motility capsule (WMC). A retrospective study of WMC data from a multi-center clinical trial and a tertiary gastroenterology clinic was performed; WMC motility parameters of contraction frequency (Ct) and area under the contraction curve were analyzed in 20-min windows 1-hour before and after awakening. T-tests compared parameters between H, NTC, and STC. Linear regression analysis was performed to determine if outlet obstruction confounded data. A receiver operating characteristic curve (ROC) demonstrated optimal Ct cut-offs to define blunted wake response. A total of 62 H, 53 NTC and 75 STC subjects were analyzed. At 20, 40, and 60 mins after awakening, STC subjects had significantly lower mean Ct when compared to H (p < 0.001) and NTC (p < 0.01). Linear regression demonstrated that outlet obstruction was not associated with a decreased wake response (β = 3.94, (CI: -3.12 to 1.00), p = 0.27). Defined at the Ct threshold of 64 at 20-min post-wake, blunted wake response sensitivity was 84% and specificity was 32% for chronic constipation. The authors concluded that findings of an impaired wake response in subjects with STC and not NTC added further evidence to neuronal dysfunction as an etiology of STC, and identified a possible temporal target for pharmacologic intervention.
Electrogastrography
Cutaneous electrogastrography (EGG) is a non-invasive test that detects gastric arrhythmias by recording the frequency and regularity of gastric myoelectrical activity. It has been used to investigate the mechanisms of gastric motility and sensation in patients with gastric motility disorders or motion sickness. By means of surface electrodes, EGG records gastric myoelectrical activity from the surface of the body. The cutaneous signals are low in amplitude, and thus must be markedly amplified. The resultant signals are heavily contaminated with noise, and visual analysis alone of EGG signals is inadequate. Consequently, EGG recordings require special methodology for acquisition, processing and analysis.
There appears to be a close relationship between gastric myoelectrical activity and gastric motility. Although it has been reported that EGG satisfactorily reflects frequency of internal gastric myoelectrical activity, there is not acceptable correlation with gastric contractions or gastric emptying. Many attempts have been made to relate EGG "abnormalities" with clinical syndromes and diseases. Although abnormalities of the electrogastrogram have been described in a variety of disorders, their specificity and their prevalence in patients with functional gastrointestinal disorders have not been determined. Electrogastrography cannot determine the etiology of detected abnormalities because there are no specific EGG patterns to differentiate one epigastric condition from another. The clinical role of EGG remains to be established, and its proponents need to demonstrate that EGG results can affect therapeutic decisions.
An American Gastroenterological Association guideline on nausea and vomiting (AGA, 2001) concluded that "the place of such tests of motor function as gastric emptying studies, electrogastrography, and manometry have not been defined, and the yield of such diagnostic studies has not been adequately compared with a therapeutic trial of an antiemetic and/or prokinetic agents." An American Gastroenterological Association guideline on constipation (AGA, 2000) stated that colonic manometry "is not generally available and is not appropriate for most patients, except in research settings." The consensus opinion of the American Motility Society Clinical GI Motility Testing Task Force on the performance and clinical utility of EGG (Parkman et al, 2003) stated that no therapies have convincingly demonstrated in controlled studies that correcting abnormalities detected by EGG improves upper gastrointestinal symptoms. Proposed clinical indications for performance of EGG in patients with unexplained nausea, vomiting and dyspeptic symptoms must be validated by prospective controlled investigations.
In an editorial on EGG, Verhagen (2005) stated that because of its low sensitivity and specificity, EGG can not be used as a diagnostic clinical tool. In certain diseases, EGG may be useful in defining a subgroup of patients. However, at present there is no evidence to support a role for EGG in the diagnostic work-up of patients or in directing therapy.
Abid and Lindberg (2007) examined if there is a correlation between electrical activity measured by EGG and contractile activity of the stomach as measured by antral-duodenal manometry (ADM). These researchers also studied if the underlying motility disorder could be predicted from EGG parameters. They compared 21 parameters measured from EGG with 8 parameters measured from ADM. The ability of EGG to identify the underlying diagnosis was tested by comparing EGG parameters for each diagnosis group against other patients. The study comprised recordings from 148 patients (125 females). Their median age was 45 years (range of 17 to 76). These investigators found few and weak correlations between EGG and ADM. Specifically the correlation between parameters reflecting the response to meal was poor (r = -0.07, p = 0.39). The discriminatory power of EGG for underlying motility disorder was also low. Patients with slow transit constipation (STC) showed a lower post-prandial power in normogastric (3.7 +/- 0.5 versus 4.0 +/- 0.5) and tachygastric (3.5 +/- 0.4 versus 3.7 +/- 0.4) regions, a lower percentage of time with normogastria [87.2% (56.5 to 100) versus 95.7% (0 to 100)], and a higher percentage of time with tachygastria [9.3% (0 to 33) versus 3.5 (0 to 100)] and bradygastria [1.8% (0 to 20) versus 0% (0 to 17.1)]. Patients with irritable bowel syndrome had a higher percentage of time with normogastria [96.5% (62.5 to 100) versus 93.3% (0 to 100)] and a less unstable dominant frequency as measured by the instability coefficient [15 (3 to 77) versus 24 (2 to 72)]. The authors concluded that EGG and ADM seem to measure different aspects of gastric motor activity but can not show a spatial correlation. The diagnostic value of EGG is poor, but EGG may have some value for the identification of patients with STC.
It should also be noted that the AGA's medical position statement on diagnosis and treatment of gastroparesis (Parkman et al, 2004) does not mention the use of electrogastrography.
Krusiec-Swidergol and Jonderko (2008) checked on reproducibility of parameters of a multi-channel electrogastrogram in adults after intake of typical, applied in EGG, test meals. Recordings of multi-channel electrogastrograms were accomplished in 4 blocks comprising 18 subjects (9 healthy volunteers and 9 patients with functional gastro-intestinal disorders) each. Every subject had 2 examinations taken 1 to 2 days apart, and a 3rd one was accomplished at least 2 weeks before or after the 2 other sessions. The registration involved a 30-min fasted and a 2-hr post-prandial period after one of the meal stimuli tested within a given block: 400 ml water, 400 g yoghurt (378 kcal), a scrambled eggs sandwich (370 kcal), a pancake (355 kcal). From among the parameters reflecting the propagation of the gastric slow waves, the average percentage of slow wave coupling (APSWC) exhibited a good (coefficient of variation for paired examinations CV(p) less than or equal to 10%) to moderate (10 less than CV(p) less than or equal to 30%) reproducibility. On the other hand, the reproducibility of the maximum dominant frequency difference and the spatial dominant power difference was found to be unsatisfactory. The reproducibility of the multi-channel EGG parameters did not differ between healthy volunteers and patients with functional gastrointestinal disorders. Gender or the kind of a test meal did not affect the reproducibility of the EGG parameters either. The medium-term reproducibility was not any worse than the short-term one. From among the parameters of a multi-channel EGG intended to quantify the propagation of slow waves, only the APSWC offers a reproducibility potentially good enough for clinical applications.
- conduction block,
- re-entry, and
- ectopic pace-making.
The stomach simulations were then applied in a torso model to identify predicted EGG signatures of normal and dysrhythmic slow wave profiles. The resulting EGG data were compared using percentage differences and correlation coefficients. Virtual EGG channels that demonstrated a percentage difference over 100% and a correlation coefficient less than 0.2 (threshold relaxed to 0.5 for the ectopic pace-maker case) were further investigated for their specific distinguishing features. In particular, anatomical locations from the epigastric region and specific channel configurations were identified that could be used to clinically diagnose the 3 classes of human gastric dysrhythmia. The authors concluded that these locations and channels predicted by simulations present a promising methodology for improving the clinical reliability and applications of EGG.
Poscente and Mintchev (2017) attempted to enhance the clinical utility of EGG, which has been recorded since 1922, but is clinically un-utilized. An innovative method to salvage the promise of EGG was proposed by introducing a preliminary procedure, while maintaining the electrodes, standardized equipment, and signal processing utilized in the well-established EGG testing of today. The proposed enhanced EGG (EEGG) protocol involves swallowing an ingestible capsule containing miniature electronic oscillator embedded in an expandable, self-disintegrable, biocompatible pseudobesoar residing in the stomach for the duration of the test. Experiments were performed on 8 mongrel dogs (23.8 ± 3.3 kg); 4 were administered an active EEGG capsule, while the rest were given a de-activated (battery removed) capsule. Pharmacologically facilitated gastric motility revealed a significant (p < 0.01) Pearson correlation between gastric motility indices obtained by force transducers implanted directly on the stomach, and the motility indices obtained by EEGG. A particular emphasis was made on preserving standard EGG-related hardware and software in order to facilitate the introduction of the proposed EEGG in environments that already utilize standard EGG testing. The expanded intra-gastric pseudobesoar containing the miniature electronic oscillator was retained during the tests, and could be disintegrated on demand. The authors concluded that EEGG is a new modality to record reliably and non-invasively gastric motility utilizing the same recording setup used in present-day plain EGG. Its clinical utilization promises to revive a non-invasive gastric testing that is fading in oblivion.
The authors stated that as with any innovative idea, a lot more needs to be done before this radically new approach in the non-invasive ambulatory assessment of gastric motility becomes a reliable clinical tool for diagnosing gastric dyspepsia and/or gastroparesis. First and foremost, the clinical community should clearly defend and loudly support the need for such a single, non-invasive and inexpensive test. Second, controlled clinical trials on humans should take place in order to explicitly show the real diagnostic value of such testing, including its sensitivity and specificity. Third, the existing EGG insurance codes should be re-visited so that the routine EGG is replaced by EEGG and it enters the clinical mainstream, rather than remain forever "a research tool" of little consequence, administered free of charge only now and again and here and there by curious investigators.
Ortigoza and associates (2018) obtained objective measures indicative of GI maturity using 3 non-invasive technologies – EGG, abdominal near-infrared spectroscopy (NIRS), and bowel sound/acoustics (AC) monitoring. These 3 approaches were used simultaneously to obtain physiologic measures of the GI system of 18 preterm and 5 term neonates who were tolerating enteral feedings. Measures of EGG slow wave voltage (EGG dominant power) and AC signal amplitude (AC dominant power) were obtained after spectral density analysis. Mean abdominal regional saturations (A-rSO2) were obtained directly from NIRS. The relationship of these 3 measures with post-menstrual age (PMA) was assessed. The results of the 3 methods differed depending on whether the measurements were pre-prandial or post-prandial. Post-prandial EGG dominant power increases with PMA (r = 0.67, p = 0.003), both pre- and post-prandial abdominal NIRS mean regional saturation increase with PMA (r = 0.73, p < 0.001 and r = 0.55, p = 0.009), and post-prandial AC dominant power (at 300 to 500 Hz) increases with PMA (r = -0.48, p = 0.025). The authors concluded that EGG, abdominal NIRS, and AC, when used simultaneously, can provide objective and synergistic measures that correlate with PMA. They stated that these findings may be helpful in the assessment of feeding readiness because they reveal quantitative measures suggestive of the developmental process of the gut. These preliminary findings need to be validated by well-designed studies.
Lim and colleagues (2018) stated that minimal change esophagitis (MCE) is a reflux disease without mucosal breaks, known to be partially associated with abnormal gastric motor function; EGG is used to assess gastric motor function in a non-invasive fashion. These investigators determined the relationship between MCE and gastric myo-electrical activity (GME) recorded on EGG in children. They retrospectively assessed the records of 157 children without underlying disease who underwent both EGG and upper GI endoscopy between January 2010 and June 2015. The children were stratified according to the appearance of the esophagus (normal versus MCE). Between-group differences in EGG parameters and their correlation with each MCE finding were statistically analyzed. Only the power ratio, 1 of the EGG parameters analyzed, differed significantly between the 2 groups (MCE, 1.68 ± 3.37 versus normal, 0.76 ± 1.06; p < 0.05), whereas the other parameters, such as dominant frequency, dominant power, and the ratio of abnormal rhythm, showed no differences. Among children with MCE, significant correlations were noted between erythema and power ratio (p < 0.05), friability and post-prandial dominant frequency (p < 0.05), and edema and/or accentuation of mucosal folds and pre-prandial frequency (p < 0.05). Helicobacter pylori (H. pylori) infection correlated with post-prandial arrhythmia (MCE, 33.59 ± 15.52 versus normal, 28.10 ± 17.23; p < 0.05); EGG parameters did not differ between children with normal esophagus and those with biopsy-proven chronic esophagitis. The authors concluded that in children with MCE, gastric dysmotility may affect the development of MCE, manifesting as EGG abnormalities; H. pylori infection may also affect GME. Moreover, they stated that larger prospective investigations are needed to confirm these findings.
The authors stated that this study had several drawbacks. First, the group of children with MCE was significantly larger than the group of children with normal esophagus, and the age distribution of the 2 groups was also significantly different. This drawback was associated with the retrospective, single-center design of this study. Second, these investigators only measured the correlation of each EGG parameter with each endoscopic finding, and did not consider any objective measures of disease severity. Third, the exact relevance of each EGG parameter remained unclear. Moreover, these researchers did not assess the correlation between EGG parameters and endoscopic findings in children with normal esophagus. Fourth, although 24-hour esophageal pH monitoring represents a good evaluation for the diagnosis of gastro-esophageal reflux disease (GERD) of non-erosive type (NERD), they could not perform 24-hour esophageal pH monitoring in this study because of the reluctance of the pediatric patients and their parents. Finally, there was no follow-up evaluation of children with MCE after treatment. The authors stated that further in-depth studies with prospective design and larger sample size, and covering several age groups, are necessary. Specifically, a study on whether the severity of symptoms, recurrence, medication, or other medical conditions and evaluations are reflected in EGG parameters would be helpful.
Bhat and colleagues (2021) noted that GERD is a commonly diagnosed GI disorder, with a substantial impact on the quality of life (QOL). The underlying pathophysiology of GERD is multi-factorial and incompletely understood. Abnormal gastric electrical activity, measured using EGG, may contribute. These investigators systematically reviewed and meta-analyzed the existing literature in which EGG was used in patients with GERD. Databases were systematically searched for studies using EGG in adults with GERD. The primary outcome was the percentage of recording time in the normo-gastric frequency range. Secondary outcomes were dominant frequency, dominant power, power ratio and prevalence of any EGG abnormality. A total of 591 subjects (427 patients with GERD; 164 healthy controls) from 13 studies were included. GERD patients spent 17.3% (SMD - 1.18, 95% CI: - 1.84 to - 0.52) and 18.7% (SMD - 1.11, 95% CI: - 1.55 to - 0.68) less of the pre-prandial and post-prandial recording time in normo-gastric frequency ranges, respectively, compared to healthy controls. The dominant frequency, dominant power and power ratio were not significantly different to healthy controls in the pre-prandial and post-prandial periods. The pooled prevalence of any EGG abnormality was significantly greater in patients with GERD than in healthy controls [46% (95% CI: 39% to 64%) versus 10% (95% CI: 4% to 23%); p < 0.0001]. Correlations between GERD symptoms and EGG recordings were inconsistently studied; EGG techniques were heterogeneous. The authors concluded that consistent abnormalities in gastric slow-wave activity, as measured by EGG, were identified in adults with GERD. Moreover, these researchers stated that further investigation into these abnormalities using novel emerging electrophysiology techniques is desirable, to better define their contribution toward GERD pathophysiology.
Kim (2024) stated that high-resolution electrogastrography (HR-EGG) presents a new paradigm in diagnosing and treating functional gastrointestinal disorders (FGID). Unlike traditional electrogastrography, HR-EGG allows for a more precise analysis of the gastric electrical activity, offering improved diagnostic accuracy. Recent studies have revealed the clinical potential of HR-EGG, especially in detecting abnormal electrical patterns in patients with functional dyspepsia and gastroparesis, supporting the development of novel therapeutic strategies. The non-invasive HR-EGG method has shown promise in identifying new biomarkers. Moreover, further integration of artificial intelligence (AI), is expected to enhance diagnostic efficiency and develop more refined treatment models for FGID.
Gastric Emptying Breath Testing
The Gastric Emptying Breath Test (GEBT) is a non-radioactive, non-invasive, orally administered test, intended for use in the measurement of emptying of solids and aid in the diagnosis of delayed gastric emptying (gastroparesis) in symptomatic adults. The GEBT incorporates a stable isotope carbon-13, denoted as 13C, in the GEBT test meal.
GEBT was developed to purportedly aid in the diagnosis of delayed gastric emptying, known as gastroparesis. This condition is characterized by slow or nonmovement of food from the stomach to the small intestine due to improper contractions of stomach muscles. Gastroparesis may result from conditions such as Parkinson’s disease, diabetes or following intestinal surgery. Gastric scintigraphy is considered the gold standard for diagnosing gastroparesis.
The GEBT is conducted over a four hour period after an overnight fast and reportedly measures how fast the stomach empties solids by measuring carbon dioxide in an individual’s breath. Before the test begins, baseline breath tests are conducted and the individual eats a specially made protein test meal enriched with carbon-13. This substance is then measured via breath testing at multiple time points after the meal to determine the rate of gastric emptying.
In March 2016, Carin Diagnostics, formerly known as Advanced Breath Diagnostics, announced the release of the U.S. FDA approved 13C-Spirulina Gastric Emptying Breath Test (GEBT) intended for measurement of the rate of solid-phase gastric emptying and aid in the diagnosis of gastroparesis in symptomatic adults. The Cairn GEBT helps to identify gastroparesis by measuring the rate of excretion of a special form of carbon dioxide in the patient's breath. Patients consume a precisely-formulated egg mixture containing pharmaceutical-grade Spirulina platensis, a nutritional blue green algae, that has been enriched with carbon-13. Consuming the 13C-enriched test meal gives rise to 13CO2. The test system utilizes a gas isotope ratio mass spectrometer for the measurement of the ratio of 13CO2 to 12CO2 in breath samples (BioSpace, 2016).
Camilleri (2018) states that alternatives to scintigraphy include 13C breath testing using spirulina incorporated into a solid meal; however, while the test has the "advantage of avoiding radiation that is associated with scintigraphy, further studies are needed before they can be routinely recommended for evaluation of delayed gastric emptying".
The spirulina 13C breath test was approved by the US Food and Drug Administration to diagnose gastroparesis in April 2015. Approval was based in part on a prospective, single-site, cohort study (PRO-DC-004) of 115 adult patients who underwent simultaneous scintigraphy and spirulina 13C breath test to validate the GEBT for use in diagnosis and monitoring of delayed gastric emptying. The analysis of effectiveness was based on the comparison of GEBT and scintigraphy at six different time points. Results from this validation study showed that the GEBT demonstrated specificity, as compared to scintigraphy, ranging from 89%-98% (between 45 and 240 minutes). At 80 percent specificity, the 13C-spirulina breath test samples at 150 and 180 minutes had a combined sensitivity of 89 percent for delayed gastric emptying (FDA, 2015; Camilleri, 2018; Szarka et al, 2008). However, additional studies are needed to validate these results before 13C breath tests can be used routinely (Camilleri, 2018).
Sangnes et al (2019) aimed to compare gastric emptying of radiopaque markers (ROM) with GEBT in the evaluation of patients with diabetes and symptoms compatible with gastroparesis. The authors evaluated 45 patients with type 1- or type 2 diabetes who had symptoms of gastroparesis. The main strength of the study was that all patients were on intravenous glucose-insulin infusion during testing, thereby minimizing the glucose level’s effect on gastric emptying, as well as avoiding iatrogenic hypoglycemia. The authors found that 40% of patients had delayed gastric emptying of ROM, while 55% had delayed gastric emptying of GEBT. Correlation between ROM and GEBT was not significant. Compared to GEBT, sensitivity for a positive ROM test was 0.52, while specificity was 0.74. In women, they found a higher specificity of 0.92, sensitivity 0.47. Difference in HbA1c between patients with positive and negative results was of borderline significance for both tests. GEBT (p=0.008) correlated with HbA1c. Patients with any late complications of diabetes had higher gastric retention of ROM (p=0.028), while patients with polyneuropathy (p=0.014) and diabetic wounds (p=0.004) had slower emptying with GEBT. None of the methods identified significant associations between gastric emptying and symptom scores, age or diabetes duration. The authors concluded that as a measure of gastric emptying, the ROM test has benefits of being affordable and available. Compared to GEBT, the method has low diagnostic reliability; however, before continued use, the authors recommend additional studies validating the test in diabetes patients.
Helicobacter Pylori Infection - A Risk Factor for Irritable Bowel Syndrome
Li et al (2020) stated that in recent years, the incidence of IBS has gradually increased, and it is considered as one of the most common functional GI diseases. However, the etiology of IBS is still unclear, and expectations are rising for more targeted treatments. Many clinical trials have examined the link between Helicobacter pylori (H. pylori) and IBS, with different conclusions; thus, these investigators carried out a meta-analysis to examine if there is an association between H. pylori and IBS, which is of great significance for targeted treatment of IBS. They conducted a systematic review and meta-analysis of the association between H. pylori and IBS. They searched PubMed, Embase, Medline and the Cochrane Library to collect related studies; OR was used to describe the ratio of the probability of the H. pylori infection occurring in IBS patients versus the controls. Heterogeneity was assessed by subgroup and meta-regression analysis. A total of 8 studies (1,861 patients) assessed the association between H. pylori infection and IBS. The OR of H. pylori in IBS patients compared to controls was 1.32 (95% CI: 0.94 to 1.87; p = 0.11). Subgroup analyses showed a difference between IBS patients diagnosed with Roman III criteria and those diagnosed with non-Roman III criteria. The authors concluded that the findings of this study suggested that H. pylori may have a positive effect on the development of IBS. Although the differences were not statistically significant, there were significant differences among subgroups of patients. Considering the limitations and heterogeneity, high quality studies are needed to further examine the effect of H. pylori on the development of IBS.
Fujimori (2021) noted that H. pylori infection causes changes to the intestinal flora, such as small intestinal bacterial overgrowth, and increases gastric acid secretion-stimulating GI hormones, mainly gastrin, due to a decrease in gastric acid caused by atrophic gastritis. Furthermore, the cellular components of H. pylori travel through the intestinal tract, so the bacterial infection affects the immune system; thus, the effects of H. pylori infection are observed not only in the stomach and the proximal duodenum but also in the small and large intestines. Meta-analyses reported that H. pylori-infected individuals had an increased risk of colorectal adenoma and colorectal cancer. Moreover, a recent study reported that the risk of developing colorectal cancer (CRC) was increased in subjects carrying H. pylori vacuolating cytotoxin A antibody. Additionally, it has been reported that H. pylori infection exacerbates the symptoms of Fabry's disease and familial Mediterranean fever (FMF) attack and is involved in irritable bowel syndrome (IBS) and small intestinal ulcers. On the other hand, some studies have reported that the frequency of ulcerative colitis (UC), CD, and celiac disease was low in H. pylori-infected individuals; therefore, H. pylori infection is considered to have various effects on the small and large intestines. However, few studies have reported on these issues, and the details of their effects have not been well elucidated; thus, additional studies are needed.
Wang et al (2022) stated that the relationship between H. pylori infection (HPI) and IBS remains controversial. In a systematic review and meta-analysis, these investigators examined the relationship between HPI and IBS based on the current evidence. They carried out a systematic literature search in electronic databases (PubMed, Embase, and the Cochrane library) by computer to identify all reports published before August 8, 2021. The OR and CI were calculated to evaluate the association between HPI and IBS. Subgroup analyses were carried out for further assessment and exploration of heterogeneity sources. Furthermore, these researchers evaluated publication bias via funnel plots, Egger's test, and Begg's test. Finally, they performed a sensitivity analysis to examine the robustness of the results. A total of 13 studies with 13,173 subjects were included in the meta-analysis. The pooled OR of the association between HPI and IBS was 1.03 (95% CI: 0.80 to 1.31; p = 0.84). The adjusted OR of the association between HPI and IBS after excluding the studies with confounding factors defined by the authors was 1.29 (95% CI: 1.03 to 1.62; p = 0.03). These investigators found a positive association between HPI and IBS-D (diarrhea subtype) (OR: 1.54; 95% CI: 1.22 to 1.95; p = 0.0003). The OR of the relationship between cytotoxin-associated gene A (Cag A) positive HPI and IBS was 4.3 (95% CI: 0.51 to 36.17; p = 0.18). The authors concluded that the likelihood of HPI in IBS patients was relatively higher than that of non-IBS participants; but not statistically significant, implying that HPI was not significantly associated with IBS, albeit these researchers may have under-estimated this association. Moreover, these investigators found a positive association between HPI and IBS-D. They also observed an increased likelihood of Cag-A positive HPI in IBS patients than that of non-IBS participants but not statistically significant. These researchers stated that additional high-quality prospective studies are needed to examine the relationship between HPI and IBS. Moreover, the specific role of Cag A in the pathogenic mechanism of IBS remains unclear, and relevant experimental studies are suggested to study this issue.
The authors stated that this meta-analysis had several drawbacks. First, potential confounding bias still exists. These investigators did not consider the impacts of age, sex, or medical history. Second, various kinds of IBS diagnostic criteria and HP detection methods were used in the included studies. Due to the various sensitivities and specificities of IBS diagnostic criteria and HP detection methods, potential observation bias may be present. For instance, HP serological test may cause a pseudo-positive result because of the past-infection patients. Third, there was significant heterogeneity that should be treated with caution. The heterogeneity of the overall association between HPI and IBS was noteworthy, although these researchers examined its sources considering 5 factors via subgroup analysis and identified the primary source of the heterogeneity as study design; the high heterogeneity existed in the relationship between Cag A-positive HPI and IBS. Fourth, the relationship between HPI and different subtypes of IBS was different, which meant the overall relationship between HPI and IBS may be impacted by this difference. It is suggested to investigate the relationship between HPI and different subtypes of IBS separately instead of simply studying the overall relationship between HPI and IBS.
Immunoglobulin G Antibody Test for Food Triggers Associated with Irritable Bowel Syndrome
Irritable bowel syndrome (IBS) is a common digestive condition characterized by recurring abdominal pain, bloating, and changes in bowel habits, such as diarrhea or constipation, often triggered by stress or specific foods, with no visible signs of damage to the digestive tract. While IBS can be very uncomfortable, it is not considered a serious, or life-threatening, disease. IBS can usually be managed with dietary changes and lifestyle modifications. Treatment may also consist of the use of medication (e.g. anti-diarrheal, laxatives, antispasmodics) to manage specific symptoms.
The inFoods IBS (Biomerica, Inc.) platform is an ELISA-based blood test that uses immunoglobin G (IgG) antibodies to help identify food triggers that have been found to worsen IBS symptoms. The panel analyzes for 18 foods found relevant to IBS which could elicit an immune response (IgG immunoreactivity) that is elevated above a normal level for the particular food item.
This test can be done in the home via a fingerstick, with the sample being sent to the laboratory for analysis. Results are typically available within 2 weeks and are reported as "Yes or No Results", as each food in the panel has an individual cut-off value to differentiate between "normal" and "elevated" immune responses. This targeted IBS food panel could be used to establish a manageable elimination diet for symptom relief.
Biomerica's inFoods IBS is considered a laboratory developed test (LDT) and has not received FDA clearance or approval.
Published peer-reviewed literature suggests a potential link between IgG antibody responses and IBS symptoms. However, the studies were limited to small sample sizes, single-center facility, IgG tests not adequately designed for persons with IBS, and lack of well-designed control diets (Biomerica, 2025).
There are no published peer-reviewed literature specific to the inFoods IBS test indexed in PubMed, U.S. National Library of Medicine (NLM) which is part of the National Institutes of Health (NIH).
Although not currently indexed in PubMed, Biomerica announced findings from a clinical trial published in "Gastroenterology", which demonstrate that participants who adhered to a personalized diet therapy based on the inFoods IBS test results experienced greater symptom improvement compared to those following a sham (placebo) elimination diet.
The purported study was a randomized, multicenter, double-blind, placebo-controlled trial that enrolled 238 IBS patients in the United States. Each patient was tested for IgG antibody responses to 18 common IBS trigger foods using the inFoods IBS panel. Patients were then randomly assigned to one of two groups: (i) treatment group which eliminated actual foods identified by the inFoods test, or (ii) control group followed a sham diet that removed foods for which the patient tested negative with the inFoods IBS test and consumed in a similar amount. The study found that 59.6% of the patients in the treatment group who eliminated their identified trigger foods met the FDA-standard target for abdominal pain reduction, compared to 42.2% in the control group. Notably, the benefits were most pronounced in persons with IBS-C (constipation-predominant IBS) and IBS-M (mixed constipation and diarrhea). Moreover, 67.1% of IBS-C patients in the treatment group met the FDA target for reduction in pain, versus 35.8% in the control group, and 66% of IBS-M patients in the treatment group experienced a reduction in pain that met the FDA target, compared to 29.5% in the control group. (Biomerica, 2025).
Malabsorption Evaluation Panel
The Malabsorption Evaluation Panel is used for: (i) evaluation of patients with suspected malabsorption, as suggested by chronic diarrhea, unexplained weight loss, or nutritional deficiencies; (ii) differentiation between causes of malabsorption, specifically inflammatory conditions, pancreatic insufficiency, and osmotic diarrhea; and (iii) detection of protein-losing enteropathy that may be associated with an underlying malabsorption. The panel tests for alpha-1 antitrypsin, calprotectin, pancreatic elastase, and reducing substances. However, there is a lack of evidence regarding the clinical value of this Panel.
Wireless Motility Capsule (SmartPill)
An approach for evaluating gastric motility function in patients with functional dyspepsia and other upper functional gastrointestinal disorders is the use of an ambulatory diagnostic test pill, the SmartPill (SmartPill Corporation; Buffalo, NY). Wireless gastrointestinal (GI) motility monitoring is a diagnostic procedure performed to evaluate suspected gastroparesis (delayed gastric emptying) or colonic transit time for chronic constipation. During wireless GI motility monitoring, the individual swallows a small capsule (approximately the size of a multivitamin) that contains sensors to measure peristaltic pressure, pH and temperature. As the capsule moves through the GI tract, radiofrequency signals are transmitted to a wireless data receiver, which is usually worn on the individual’s belt. After excretion, the receiver is returned to the physician, who downloads the data and analyzes the results. An example of a wireless GI motility monitoring system includes, but may not be limited to, the SmartPill GI monitoring system 2.0.
On July 20, 2006, the Unites States Food and Drug Administration cleared the SmartPill GI Monitoring System through the 510(k) process for use as an aid in evaluating patients with suspected motility disorders such as gastroparesis. This wireless, ingestible, medical device assesses pH and pressure in the gastrointestinal lumen. When the capsule reaches the duodenum, the change in pH (from acidic to alkaline) indicates this transition, allowing an assessment of gastric emptying. The single-use, disposable, wireless capsule is slightly larger than a multi-vitamin (26 mm by 13 mm). As it passes through the gastrointestinal tract, miniaturized sensor technology measures pressure, temperature, and pH, as well as real and elapsed time. Acquired data are continuously transmitted over very low power radiofrequencies to a small receiver that can be worn on the patient's belt. Although the capsule normally has a transit time ranging from 24 to 48 hours, it is capable of transmitting data continuously for more than 72 hours in patients with reduced motility. Once the device has passed, the data set is down-loaded from the receiver to a laptop computer, and special software provides tools for data analysis and a graphical user interface that indicates when gastric emptying, small bowel/large bowel transit, and total gastrointestinal tract transit time of the capsule has occurred. It should be noted that the SmartPill is intended to supplement, not replace, current gastro-intestinal motility procedures such as endoscopy, duodenal manometry, and gastric emptying scintigraphy.
Kuo and associates (2006) reported their experience with the use of the SmartPill in 86 healthy subjects and 60 patients with documented gastroparesis by scintigraphy. The wireless capsule had a moderate sensitivity and specificity for half-time gastric emptying measurement (71% and 74%, respectively). These findings, originally reported in an abstract, were subsequently published in a full-length article. Kuo et al (2008) compared gastric emptying time (GET) and gastric emptying scintigraphy (GES) by assessing their correlation, and compared GET and GES for discriminating healthy subjects (n = 87) from gastroparetics (n = 61). Fasted subjects were ingested capsule and [(99m)Tc]-SC radiolabeled meal. Images were obtained every 30 minutes for 6 hours. Gastric emptying time and percentage of meal remaining at 2/4 hours were determined for each subject. The sensitivity/specificity and receiver operating characteristic analysis of each measure were determined for each subject. Correlation between GET and GES-4 hour was 0.73 and GES-2 hour was 0.63. The diagnostic accuracy from the receiver operating characteristic curve between gastroparetics and healthy subjects was GET = 0.83, GES-4 hour = 0.82 and GES-2 hour = 0.79. The area-under-the-curve analysis of overall accuracy indicated that there were no statistically significant differences between the SmartPill and scintigraphy for detection of gastroparesis. The 300-min cut-off time for GET gives sensitivity of 0.65 and specificity of 0.87 for diagnosis of gastroparesis. The corresponding sensitivity/specificity for 2- and 4-hour standard GES measures were 0.34/0.93 and 0.44/0.93, respectively. Although the SmartPill was able to distinguish normal state from disease, a case-control study is insufficient for evaluating test characteristics. Prospective, randomized, controlled trials are needed to ascertain the clinical value of the SmartPill. Furthermore, since the SmartPill itself does not empty like a meal from the stomach, the technology is likely to only provide an estimate of upper gastro-intestinal transit.
Cassilly et al (2008) examined if the SmartPill wireless pH and pressure capsule given with a meal empties from the stomach with return of the fasting phase III migrating motor complex (MMC) or during the fed pattern with the solid meal. A total of 15 normal subjects underwent antro-duodenal manometry and ingestion of a radio-labeled meal and the SmartPill. In 5 subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radio-labeled water. The SmartPill emptied from the stomach within 6 hours in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 +/- 22 mins) correlated strongly with time to the first phase III MMC (239 +/- 23 mins; r = 0.813; p < 0.01) and correlated moderately with solid-phase gastric emptying (r = 0.606 with T-50% and r = 0.565 with T-90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In 5 subjects, the SmartPill emptied with isolated distal antral contractions. In 5 subjects ingesting only water, SmartPill gastric residence time (92 +/- 44 mins) correlated with the time to the first phase III MMC (87 +/- 30 mins; r = 0.979; p < 0.01). The SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid-phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non-digestible solid.
A study that compared the SmartPill with radiopaque markers for detection of delayed colonic transit in chronically constipated versus normal adults found that sensitivity of detection was higher for the SmartPill but did not report whether this increase was statistically significant. Rao et al (2009) assessed regional and colonic transit time with the SmartPill in constipated and healthy subjects and compared this with a radiopaque market. Seventy-eight constipated (Rome II) and 87 healthy subjects ingested a 260-kcal meal, a radiopaque marker capsule, and the SmartPill. Subjects wore a data receiver and kept daily stool diaries for 5 days. SmartPill recordings assessed colonic transit time, whole-gut transit time, small-bowel transit time, and gastric emptying time. Abdominal radiographs on days 2 and 5 assessed radiopaque marker transit. Sensitivity, specificity and receiver operating characteristics (ROCs) of each technique and utility were compared. Gastric emptying time, colonic transit time, and whole-gut transit time were slower (p < 0.01) in constipated subjects than controls. Colonic transit time was slower in women than men (p = 0.02). Day 2 and day 5 radiopaque marker transits were slower (p < 0.001) in constipated subjects. Correlation of the SmartPill colonic transit time with radiopaque markers expelled on day 2/day 5 was r = 0.74/r = 0.69 in constipation, and r = 0.70/r = 0.40 in controls, respectively. The diagnostic accuracy of the SmartPill colonic transit time to predict constipation from ROC was 0.73, with a specificity of 0.95. The authors reported that these were comparable with those of day 5 ROM (ROC, 0.71; specificity, 0.95).
Maqbool et al (2009) compared the SmartPill with whole gut transit scintigraphy to determine whether the SmartPill system could serve as a test for measurement of whole gut motility and transit. A total of 10 healthy, asymptomatic subjects underwent simultaneous whole gut scintigraphy and SmartPill assessment of whole gut transit. All subjects completed the study per protocol and experienced natural passage of the pill. Capsule residence time in the stomach correlated with percent gastric retention of the Tc-99 radiolabel at 120 mins (r = 0.95) and at 240 mins (r = 0.73). Small bowel contraction-min(-1) measured by the SmartPill correlated with small bowel transit% (r = 0.69; p = 0.05) and with isotopic colonic geometric center at 24 hours following ingestion (r = 0.70, p = 0.024). Capsule transit time correlated with scintigraphic assessment of whole gut transit. The authors concluded that SmartPill capsule assessment of gastric emptying and whole gut transit compares favorably with that of scintigraphy. Wireless capsule motility shows promise as a useful diagnostic test to evaluate patients for gastro-intestinal transit disorders and to study the effect of prokinetic agents on gastro-intestinal transit.
A study comparing the SmartPill to radio-opaque markers in persons with constipation found the SmartPill to be somewhat less accurate, if radio-opaque markers are considered the gold standard for assessing colonic transit. Camilleri et al (2010) proposed to validate the SmartPill wireless motility capsule, that measures pH, pressure and temperature, to radio-opaque marker measurement of colon transit in patients with symptomatic constipation evaluated at multiple centers. Of 208 patients recruited, 158 eligible patients underwent simultaneous measurement of colonic transit time (CTT) using radio-opaque markers (Metcalf method, cut-off for delay greater than 67 hours), and wireless motility capsules (WMC) (cut-off for delay greater than 59 hours). The study was designed to demonstrate substantial equivalence, defined as diagnostic agreement greater than 65% for patients who had normal or delayed radioopaque marker transit. Fifty-nine of 157 patients had delayed radio-opaque marker colonic transit. Transit results by the 2 methods differed: radio-opaque marker median 55.0 hours [IQR 31.0 to 85.0] and Smartpill (43.5 hours [21.7 to 70.3], p < 0.001). The positive percent agreement between Smartpill and radio-opaque markers for delayed transit was approximately 80%; positive agreement in 47 by SmartPill/59 by radio-opaque marker or 0.796 (95% confidence inerval [CI]: 0.67 to 0.98); agreement versus null hypothesis (65%) p = 0.01. The negative percent agreement (normal transit) was approximately 91%: 89 by Smartpill/98 by radioopaque marker or 0.908 (95% CI: 0.83 to 0.96); agreement versus null hypothesis (65%), p = 0.00001. Overall device agreement was 87%. The authors stated that there were significant correlations (p < 0.001) between radio-opaque markers and Smartpill transit (CTT [r = 0.707] and between radio-opaque markers and combined small and large bowel transit [r = 0.704]). There were no significant adverse events. The authors stated that there are potential pitfalls with using all capsules to measure gut transit including technical failures, inability to swallow the capsule, the potential for non-passage of or intestinal obstruction by the capsule in stenosing gut disorders, and greater cost relative to the radio-opaque marker transit method. Application of the Smartpill is contraindicated in patients with known esophageal or intestinal strictures, and children under 18 years of age, in whom validation studies have not yet been completed.
Tack and Janssen (2010) reviewed recent progress in gastro-duodenal motility and sensitivity in health and in disease. The authors stated that although gastric and small intestinal motility remain an important focus of research, including the application of the SmartPill wireless motility monitoring capsule, duodenal sensitivity and low-grade duodenal inflammation are new areas of interest in the pathogenesis of functional dyspepsia. A number of genetic polymorphisms associated with functional dyspepsia are being investigated, but large-scale studies are still lacking.
Timm and colleagues (2011) noted that the SmartPill has not been validated with dietary interventions. Thus, these researchers conducted a controlled cross-over trial to examine if the device could detect a significant difference in transit time after 10 healthy subjects (5 men and 5 women) consumed 9 g of wheat bran (WB) or an equal volume, low-fiber control for 3 days. A paired-t test was used to determine differences in transit times. Colonic transit time decreased by 10·8 (S.D. 6·6) hours (p = 0·006) on the WB treatment. Whole-gut transit time also decreased by 8·9 (S.D. 5·4) hours (p = 0·02) after the consumption of WB Gastric emptying time (GET) and small-bowel transit time did not differ between treatments. Despite encouraging results, the present study had several limitations including short duration, lack of randomization and unusable data due to delayed gastric emptying of the capsule. With minimal participant burden, the SmartPill technology appears to be a potentially useful tool for assessing transit time after a dietary intervention. This technology could be considered for digestive studies with novel fibers and other ingredients that are promoted for gut health.
Willis and associates (2011) explored the feasibility and sensitivity of a new technology for measuring GET in appetite research, and compared appetite after subjects consumed macronutrient- and fiber-matched liquid and solid meals. A total of 14 women (body mass index [BMI] of 21.2 +/- 0.3) participated in this randomized, cross-over study. On 2 separate days, fasted subjects consumed liquid (fruit juices and skim milk) and solid (oatmeal, blueberries, and apples) breakfasts. Both meals had 10 g of fiber and 410 kcal. Gastric emptying time was assessed with the SmartPill GI Motility System, appetite was assessed with visual analog scales, and food intake was measured at lunch. Despite the same amount of fiber, GET was about 1 hour longer after the oatmeal than after the liquids. Subjects were less hungry after the oatmeal than after the liquids. Satisfaction and fullness were marginally improved with the oatmeal compared to the liquids. There was a negative association between GET and hunger. Lunch-time food and beverage intake did not differ between treatments. The authors concluded that the SmartPill appears feasible and sensitive in appetite research, but has limitations.
The BlueCross BlueShield Association Technology Evaluation Center (BCBSA, 2012) concluded that the wireless motility capsule does not meet the TEC criteria. The TEC assessment concluded that the limited body of evidence on the diagnostic characteristics of SmartPill does reveal correlations between SmartPill and other tests that indicate some capability to distinguish diseased from non-diseased persons. The assessment stated, however, because of the types of subjects included in the studies, particularly healthy patients, and the lack of a reference standard for the disease of interest (slow-transit constipation) in some studies, the diagnostic characteristics of SmartPill are uncertain. The assessment noted that there are no studies that ascertain whether use of the SmartPill in addition to or instead of alternative methods of diagnosis improves patient outcomes.
The Federal Agency for Healthcare Research and Quality (AHRQ, 2011) has commissioned a comparative effectiveness review of the wireless motility capsule compared to other diagnostic technologies for evaluating gastroparesis and constipation. The AHRQ has stated that the the current gold standard diagnostic methods for motility disorders include scintigraphy and the use of radiopaque markers. In discussing the considerations for conducting the review, the AHRQ explained: "The SmartPill procedure has been described as having advantages to current standard testing methods including less radiation exposure, a more standardized diagnostic approach, convenience, and a more detailed diagnostic profile; however, the technology may have limited patient selection, contraindications, and may not always avoid radiation exposure" Regarding the current available evidence, the AHRQ stated that "[t]he SmartPill has not been studied extensively in the context of other testing methods, and most available studies have been sponsored by the manufacturer."
The AHRQ (2012) review will address several controversies surrounding the use of the SmartPill wireless motility capsule for gastroparesis. One controversy identified by AHRQ is whether grading the severity of gastric emptying delay affects decisions about patients. They plan to address this question by evaluating data on how treatment decisions differ between scintigraphy and the wireless motility capsule. Another controversy that they plan to address is the lack of information regarding whether or not scintigraphy or wireless motility capsule testing could offer any guidance in assessing response to treatment or whether they would remain purely diagnostic tools. The AHRQ review plans to address this issue by looking for data on treatment response in terms of patient-reported outcomes. The AHRQ stated that it is unclear which populations would benefit most from the wireless motility capsule or which order of testing is best to diagnose patients. The AHRQ noted that the wireless motility capsule testing is currently being used in a complementary fashion as an addition to reference standard tests like scintigraphy. The AHRQ stated that it is controversial whether the wireless motility capsule can replace or should supersede other testing methods.
The AHRQ review (2012) will also examine the evidence for the wireless motility capsule in constipation. Among the advantages of capsule testing identified by AHRQ is that it provides a more complete picture of colonic transit (like whole bowel scintigraphy might if it were more widely available); whereas, radiopaque marker testing, the current reference standard, only offers static imaging. The AHRQ stated however, that it is uncertain at this point whether all the extra data will be useful to change outcomes in any way. The AHRQ stated that more studies must be done as the wireless motility capsule gets adopted into wider use. The AHRQ review will address the controversy regarding the role of wireless motility capsule testing in the diagnostic evaluation of constipation; the AHRQ commented that some experts think that the wireless motility capsule would likely be a complementary test rather than an independent test for patients with this disease.
- defined prevalence of generalized dysmotility using WMC,
- related to symptoms in suspected regional delay,
- compared results of WMC testing to conventional transit studies to quantify new diagnoses, and
- assessed the impact of results of WMC testing on clinical decisions.
Wireless motility capsules transits were analyzed in 83 patients with suspected gastroparesis, intestinal dysmotility, or slow transit constipation. Isolated regional delays were observed in 32% (9% stomach, 5% small bowel, 18% colon). Transits were normal in 32% and showed generalized delays in 35%. Symptom profiles were similar with normal transit, isolated delayed gastric, small intestinal, and colonic transit, and generalized delay (p = NS). Compared to conventional tests, WMC showed discordance in 38% and provided new diagnoses in 53%. Wireless motility capsules testing influenced management in 67% (new medications 60%; modified nutritional regimens 14%; surgical referrals 6%) and eliminated needs for testing not already done including gastric scintigraphy (17%), small bowel barium transit (54%), and radio-opaque colon marker tests (68%). The authors concluded that WMC testing defines localized and generalized transit delays with suspected gastroparesis, intestinal dysmotility, or slow transit constipation. Symptoms do not predict the results of WMC testing. Wireless motility capsules findings provide new diagnoses in greater than 50%, may be discordant with conventional tests, and can influence management by changing treatments and eliminating needs for other tests. They stated that these findings suggested potential benefits of this method in suspected dysmotility syndromes and mandate prospective investigation to further define its clinical role.
Brun et al (2012) evaluated the ability of WMC to detect phase III MMC and correlated it with the simultaneous measurements by ADM. A total of 18 patients underwent simultaneous ADM and WMC. Migrating motor complexes were identified first on ADM and then correlated with WMC events occurring simultaneously. Frequency of contractions per min, area under the pressure curve (AUC), and motility index (MI) and criteria for amplitude thresholds of contractions representing MCCs on WMC tracings were defined. In 18 patients, a total of 29 MMCs were recorded by ADM. Wireless motility capsule detected 86% of MMC events measured by ADM. Hundred percent (10/10) of MMCs in stomach were detected by WMC, whereas 79% (15/19) of MMCs were detected in small bowel (SB). The sensitivity and specificity of WMC high amplitude contractions to represent phase III MMC were 90% and 71.8% in the stomach; 73.7% and 84.7% in SB, respectively, and negative predictive value was 99.9% in both regions. The authors concluded that WMC was able to detect the phase III MMCs as the high amplitude contractions with good fidelity. Wireless motility capsule does not detect the propagation of MMC. Using the pressure thresholds, WMC can detect high amplitude contraction representing phase III MMC with favorable sensitivity/specificity profile and 99.9% negative predictive value. They stated that this observation may have clinical significance, as the absence of high amplitude contractions recorded by WMC during fasting state suggested absence of MMCs; further studies are needed to determine the potential use of these results in clinical practice for diagnosis and profiling of gastro-intestinal motility disorders.
Tran et al (2012) noted that the WMC is an ambulatory non-invasive and non-radioactive diagnostic sensor that continuously samples intra-luminal pH, temperature, and pressure as it moves through the gastro-intestinal (GI) tract. These researchers summarized the data obtained in clinical trials with the WMC and discussed its role in clinical practice. The United States Food and Drug Administration has approved the SmartPill GI monitoring system for the evaluation of gastric emptying time in patients with suspected gastroparesis, the evaluation of colonic transit time in patients with suspected chronic constipation, and for the characterization of pressure profiles from the antrum and duodenum. Clinical studies have shown that WMC-measured GI transit times can distinguish patients with motility abnormalities similarly to conventional testing. However, the WMC offers the advantage of providing a full GI-tract profile, enabling the detection of multi-regional GI transit abnormalities in patients with suspected upper or lower GI dysmotility. The WMC also characterizes pressure profiles of the GI tract and impaired pressure profile limits are reported for the antrum and duodenum. In comparison with manometry, interpretations of pressure measurements obtained by the WMC are limited by an inability to detect a peristaltic pressure wave front, and further investigation is needed to develop clinical applications. The authors concluded that WMC is a novel technology offering a non-invasive, non-radioactive, standardized method to evaluate intra-luminal pH, temperature, and pressure, allowing for the measurement of gastric, small bowel, colon, and whole GI transit times. As a single ambulatory test, it allows for an assessment of isolated and diffuse motility transit abnormalities. Interpretation of frequency of contractions (Ct) measurements obtained by the WMC is limited compared with manometry testing, but continues to evolve. Clinical studies with the WMC indicated that it should be considered for the evaluation of regional and whole gut transit time in patients with suspected upper or lower dysmotility, particularly if there are concerns about multi-regional dysmotility. The drawbacks of this study were "[w]hile the WMC provides a full GI tract-transit profile in a standardized protocol, the pressure profiles are limited by nonstationary, single point pressure measurements throughout the GI tract. As a new method of measuring GI Ct, new standards need to be developed and validated before the relevance of this information is clear .... The WMC, with only one pressure sensor, is unable to detect a pressure wave front, which limits its utility in comparison to traditional manometric testing. However, with the invasive nature and limited availability of manometry, the WMC may have significant potential as further investigation continues to evolve the clinical utility of WMC pressure data. The WMC can not distinguish the absolute time of emptying of a meal or distinguish between liquid and solid emptying; rather it measures the total meal emptying. Furthermore, the WMC measures gastric emptying indirectly through the use of a physiologic meal. Scintigraphy testing leads to a more physiologic assessment of transit time. As a non-digestible capsule that needs to be ingested, the WMC should not be administered to those patients with suspected strictures, fistulas, or GI obstructive symptoms. In addition, it should be used with caution for anyone with a history of gastric bezoars, dysphagia, or disorders of swallowing, recent GI surgery, Crohn’s disease, or diverticulitis".
Rauch et al (2012) used a novel WMC to compare gastric emptying and SB transit times in critically ill trauma patients and healthy volunteers. These investigators evaluated gastric emptying, SB transit time, and total intestinal transit time in 8 critically ill trauma patients. These data were compared with those obtained in 87 healthy volunteers from a separate trial. Data were obtained with a motility capsule that wirelessly transmitted pH, pressure, and temperature to a recorder attached to each subject's abdomen. The gastric emptying time was significantly longer in critically ill patients (median of 13.9; interquartile range [IQR]: 6.6 to 48.3 hours) than in healthy volunteers (median of 3.0; IQR: 2.5 to 3.9 hours), p < 0.001. The SB transit time in critically ill patients was significantly longer than in healthy volunteers (median of 6.7 hours; IQR: 4.4 to 8.5 hours versus median of 3.8 hours; IQR: 3.1 to 4.7 hours), p = 0.01. Furthermore, the capsules passed after 10 (IQR: 8.5 to 13) days in the critical care group and 1.2 (IQR: 0.9 to 1.9) days in healthy volunteers (p < 0.001). The authors concluded that both gastric emptying and SB transit were delayed in critically ill trauma patients. The drawbacks of this study were the small number of critically ill patients, and exclusion of patients with increased intra-abdominal pressure, open abdominal injury, and exploratory laparotomies. Also, these researchers measured gastric emptying and SB transit time only once during the ICU stay because it is not possible to start a new capsule examination until the previous one has passed from the body. Although delayed gastric emptying is most common in the first 3 days after ICU admission, the authors can not exclude disturbance of intestinal motility later in the critical care course. Furthermore, both enteral feeding as well as anti-acid therapies can alter intra-luminal pH, complicating identification of the capsule's transition from the stomach to small intestine. The authors stated that "[d]espite the use of H2 blockers, all patients had a distinct pH pattern to identify the passage of the capsule. Nguyen et al has shown in a retrospective study that morphine/midazolam and propofol can alter gastric emptying. It seems that patients under propofol-based sedation have a lower incidence of delayed gastric emptying. Although sedation and analgesia requirements were similar among the critically ill group, we can not exclude that the pharmacologic effect of propofol/midazolam and fentanyl/morphine could have contributed to the prolonged gastric emptying time and small bowel transit time".
Weinstein et al (2013) stated that GERD and gastric acid hyper-secretion respond well to suppression of gastric acid secretion. However, clinical management and research in diseases of acid secretion have been hindered by the lack of a non-invasive, accurate and reproducible tool to measure gastric acid output (GAO). Thus, symptoms or, in refractory cases, invasive testing may guide acid suppression therapy. These researchers presented and validated a novel, non-invasive method of GAO analysis in healthy subjects using a wireless pH sensor, SmartPill (SP) (SmartPill Corporation, Buffalo, NY). A total of 20 healthy subjects underwent conventional GAO studies with a nasogastric tube. Variables impacting liquid meal-stimulated GAO analysis were assessed by modelling and in-vitro verification. Buffering capacity of Ensure Plus was empirically determined. SmartPill GAO was calculated using the rate of acidification of the Ensure Plus meal. Gastric emptying scintigraphy and GAO studies with radio-labelled Ensure Plus and SP assessed emptying time, acidification rate and mixing; 12 subjects had a second SP GAO study to assess reproducibility. Meal-stimulated SP GAO analysis was dependent on acid secretion rate and meal-buffering capacity, but not on gastric emptying time. On repeated studies, SP GAO strongly correlated with conventional basal acid output (BAO) (r = 0.51, p = 0.02), maximal acid output (MAO) (r = 0.72, p = 0.0004) and peak acid output (PAO) (r = 0.60, p = 0.006). The SP sampled the stomach well during meal acidification. The authors concluded that SP GAO analysis is a non-invasive, accurate and reproducible method for the quantitative measurement of GAO in healthy subjects. They stated that SP GAO analysis could facilitate research and clinical management of GERD and other disorders of gastric acid secretion. These findings from a feasibility study using health subjects need to be validated by well-designed studies using patients with gastric disorders.
Stein et al. (2013) systematically reviewed the evidence comparing wireless motility capsule (WMC) with other diagnostic tests used for the evaluation of gastroparesis and slow-transit constipation, in terms of diagnostic accuracy, accuracy of motility assessment, effect on treatment decisions, effect on patient-centered outcomes, harms, and effect on resource utilization. Twelve diagnostic studies were included evaluating wireless motility devices in adults with suspected gastroparesis and/or slow-transit constipation. All studies had one or more limitation (i.e., unclear use of same reference standard, no blinding of investigators, results based on subgroup analysis). Compared to radiopaque markers for diagnosis of slow-transit constipation, wireless motility capsules demonstrated the following: about 80% concordance in 3 studies with 293 patients; and 43% to 87% positive percent agreement and 67% to 91% negative percent disagreement in 5 observational studies with 541 adults with known or suspected constipation. Capsule retention in 0% to 16.4% in 2 studies with 247 adults and no serious adverse events in any 5 studies. This systematic review demonstrated that WMC appears to have good agreement with radiopaque markers for diagnosis of slow-transit constipation (i.e., concordance range between 64% and 87%). The evidence was insufficient to justify conclusions about effects of WMC on treatment decisions and resource utilization.
Hasler et al (2014) stated that testing to define delayed gastric emptying is needed to diagnose gastroparesis; rapid emptying is found in other patients. Commonly performed methods of gastric emptying testing include scintigraphy and breath testing. The SmartPill WMC system is FDA-approved for evaluating suspected delayed emptying in gastroparesis and functional dyspepsia. The device measures transit in the stomach, small intestine, and colon by detecting characteristic pH transitions; and quantifies pressure waves in each gut region. Wireless motility capsules gastric emptying times correlate with scintigraphic measures. Incremental benefits of WMC testing in patients with suspected gastroparesis include delineation of pressure abnormalities and small intestinal and colonic transit delays. The authors concluded that acceptance of trial data confirming usefulness of WMC testing in suspected gastric motor disorders has been hampered by small sample sizes and design limitations. They stated that ongoing multi-center studies will validate the utility of WMC methods in patients with suspected gastroparesis and other upper GI motor disorders.
Rozov-Ung et al (2014) evaluated the ability of a wireless motility capsule to detect drug effects on GET and gastric contractility. A total of 15 healthy adults were administered in random order saline, erythromycin IV 150 mg, or morphine IV 0.05 mg/kg body weight. Subjects ate a standard meal after each infusion, and subsequently ingested the motility capsule. Data were recorded for 8 hours, and the results were analyzed using the manufacturer's software. Gastric emptying time was significantly faster after erythromycin than either saline or morphine. Morphine tended to delay emptying of the capsule compared to saline. There was a trend toward a greater frequency of gastric contractions with erythromycin and a reduced frequency of gastric contractions with morphine that did not reach statistical significance. The authors concluded that a wireless motility capsule successfully detected acceleration of gastric emptying induced by erythromycin, and retardation of gastric motility caused by morphine. They stated that these results indicated that a wireless motility capsule is a promising technique to assess pharmacologic effects on gastric transit and contractility and aid in development of drugs for gastric motor disorders.
Yung and colleagues (2016) noted that there are scarce data looking at SmartPill assessment of patients with known/suspected small-bowel Crohn's Disease (CD). In a pilot study, these researchers examined the feasibility and safety of SmartPill to assess gut motility in this group. Over 1 year, patients with known/suspected CD, referred for small-bowel capsule endoscopy (SBCE), were invited to participate and 12 were recruited (5 males and 7 females, mean age of 44.2 ± 16.6 years). They underwent hydrogen breath test to exclude small-bowel bacterial overgrowth, patency capsule (Agile), and provided stool samples for fecal calprotectin (FC). Patients ingested PillCam SB2 and SmartPill 4 hours apart. Using unpublished data, 33 healthy controls also were identified for the study; p < 0.05 was considered statistically significant. Of the 12 patients enrolled, 10 underwent complete SmartPill examination (1 stomach retention, 1 drop-out). PillCam was complete in 10 (1 drop-out, 1 stomach retention). Mean fecal calprotectin was 340 ± 307.71 mcg/g. The study group had longer transit times and lower gut motility index than did the controls. The difference in motility appeared to be statistically significant (p < 0.05). Longer transit times for SmartPill (not statistically significant) may have been due to different specifications between the capsules. Limitations included transient SmartPill signal loss (5/10 studies). The authors concluded that this was the first pilot study to attempt combining SBCE and SmartPill to evaluate small-bowel CD. Data on motility in CD are scarce. Multi-modal information can provide a clearer clinical picture. Despite concerns about capsule retention in CD patients, SmartPill appeared safe for use if a patency capsule is employed beforehand. Moreover, they stated that statistical significance should be interpreted with caution given the small sample size. Other limitations of this pilot study included potential selection bias, as patients with significant SB inflammation were excluded due to fear of capsule retention, and the SmartPill signal loss (resulting in incomplete data sets in 5 /10 completed WMC examinations).
Vilz and associates (2016) stated that post-operative ileus (POI) is a frequent complication after abdominal surgery (AS). Until today, neither a prophylaxis nor an evidence-based therapy exists. This originates from the absence of objective parameters evaluating the severity and duration of POI resulting in clinical trials of modest quality. The SmartPill, a capsule which frequently measures pH value, temperature and intra-luminal pressure after swallowing, offers an elegant option for analyzing GI transit times and smooth muscle activity in-vivo. As the use in patients in the first months after AS is not covered by the marketing authorization, these researchers examined the safety and feasibility of the SmartPill immediately after surgery. In addition, they analyzed the influence of prokinetics and laxatives as well as standardized physiotherapy on post-operative bowel contractility, as scientific evidence of its effects is still lacking. The PIDuSA study is a prospective, single-center, 2-arm, open-label trial. The SmartPill will be applied to 55 patients undergoing AS having a high risk for POI and 10 patients undergoing extra-abdominal surgery rarely developing POI. The primary objective is the safety of the SmartPill in patients after surgery on the basis of adverse device effects/serious adverse device effects (ADE/SADE). The sample size suggested that events with a probability of 3% could be seen with a certainty of 80% for at least once in the sample. Secondary objective is the analysis of post-operative intestinal activity in the GI tract in both groups. Furthermore, clinical signs of bowel motility disorders will be correlated to the data measured by the SmartPill to evaluate its significance as an objective parameter for assessing POI severity. Furthermore, effects of prokinetics, laxatives and physiotherapy on post-operative peristaltic activity recorded by the SmartPill will be analyzed. The protocol was approved by the federal authority and the local ethics committee; findings will be disseminated through publications and conference presentations.
Diaz Tartera and colleagues (2017) noted that there is interest in ultimately combining endoscopy and motility assessments. Gastric emptying (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) are conveniently obtained by SmartPill WMC that records luminal pH, temperature and pressure. Reproducibility within same subjects and accuracy of software derived times (MotiliGI) were investigated for diagnostic application; GET and SBTT were separately measured using video capsule endoscopy (VCE). These researchers evaluated the same subject reproducibility of WMC, accuracy of software derived transit times and relate to Pillcam SB (small bowel) VCE motility data. A total of 73 healthy adults ingested a 260 kcal mixed meal followed by WMC tests. Food intake was permitted after 6 hours. Regional transit data was obtained for GET, SBTT and CTT, the sum yielding WGTT; 19 subjects repeated WMC tests 2 or 4 weeks later; a separate 70 underwent VCE while fasted. Visually derived data from WMC yielded GET 3.46 ± 0.27, SBTT 5.15 ± 0.21, CTT 20.76 ± 1.19 and WGTT 29.53 ± 1.28 hours (mean ± SEM). Pearson's correlation coefficients (r) against software derived results were: GET 0.78 (p < 0.0001), SBTT 0.28 (p < 0.05), CTT 0.96 (p < 0.0001), WGTT 0.99 (p < 0.0001). VCE yielded lower GET (0.71 ± 0.08 hours) and SBTT (4.15 ± 0.13 hours). The authors concluded that GET, SBTT, CTT and WGTT obtained by WMC were commensurate with literature values, including by other methods. Visually and software derived transit times had strongest correlations for CTT and WGTT; WMC yielded longer GET and SBTT than VCE, perhaps due to meal related effects on motility. This study was carried out using healthy volunteers; it did not provide any data on patients with GI motility disorders.
Rouphael et al (2017) stated that GI dysmotility is common in diabetic patients; WMC provides the transit profile of the entire GI tract in a single study. Factors affecting GI dysmotility and the use of WMC study are not clearly established in diabetic patients. In a retrospective chart review, these researchers examined the pattern of GI dysmotility using WMC and evaluated the effect of glycemic control and presence of diabetic microvascular complications on motility impairment in diabetic patients. They also examined the impact of WMC findings on clinical management. This review included patients with diabetes mellitus (DM) who underwent WMC testing at the authors’ institution from 2010 to 2015. Demographics, hemoglobin A1c (HbA1c) levels, microvascular complications, and WMC findings were obtained. Impact of WMC on clinical management was assessed. A total of 100 patients were included. Mean age was 45 ± 19 years and 76% were women; 72% had abnormal WMC testing, of which 29 (40%) had multi-regional dysmotility. There were no significant differences in demographics, diabetic microvascular complications or HbA1c levels among patients with normal and abnormal WMC testing or among patients with isolated versus multi-regional dysmotility. Information regarding subsequent clinical management was available for 47 patients. WMC testing was abnormal in 33 (70%) patients and treatment changes based on WMC results were made in 24 patients (73%). The authors concluded that in this study, almost 3/4 of the diabetic patients referred for GI motility testing were found to have motility impairment and approximately 50% had multi-regional dysmotility. Glycemic control or diabetic microvascular complications did not predict the pattern or extent of dysmotility in these patients. These investigators stated that WMC could be useful in determining treatment strategies in these patients; however, further prospective studies are needed to confirm the validity of these findings.
The authors concluded that this study had several drawbacks. First, it was a retrospective analysis of patients observed in a tertiary referral center, which may have introduced referral bias to explain the study findings. Second, this study cohort included only the diabetic patients referred for WMC testing; thus, the true prevalence and patterns of GI dysmotility in all diabetic patients was not known. Third, symptoms and response to treatment were noted as dichotomous variables, specifically as present or absent rather than being assessed by validated scales. Furthermore, the lack of association between extent of gut involvement and glycemic control might be due to Type II error. Fourth, duration of diabetes may have contributed to incidence of gut dysmotility; however, information on duration of diabetes was unfortunately not available. Of note, approximately 3/4 of the patients had type-II DM and date of diagnosis did not accurately reflect the duration of disease. Some of the drawbacks of inherent WMC testing include cost, uncertainty as to whether delayed CTT was due to true slow CTT or outlet obstruction. Another concern raised was that WMC is a large capsule and might not necessarily mimic the gastric emptying of a regular meal.
Sangnes et al. (2020) conducted a diagnostic cohort study with wide confidence intervals comparing wireless motility capsule (WMC) with gastric emptying scintigraphy (GES). Seventy-two adults with diabetes mellitus and symptoms consistent with gastroparesis were simultaneously assessed with WMC testing and GES (reference standard). There were no differences in symptom severity in patients with normal compared to severe gastric retention as measured by either WMC or GES.
Radetic et al (2021) noted that dysmotility in one region of the GI tract has been found to predispose patients to developing motility disorders in other GI segments; however, few studies have examined the relationship between gastroparesis and constipation. These investigators retrospectively reviewed 224 patients who completed 4-hour, solid-phase GES, and WMC testing to examine gastroparesis and slow-transit constipation, respectively. When available, anorectal manometry data were reviewed to evaluate for dyssynergic defecation. Patients were divided into 2 groups based on the results of the GES: 101 patients with normal gastric emptying and 123 patients with gastroparesis (stratified by severity). Differences in constipation rates were compared between the groups. Slow-transit constipation was more common in the gastroparesis group, but statistical significance was not reached (42.3% versus 34.7%, p = 0.304). Univariate logistical regression analysis found no association between slow-transit constipation and gastroparesis (odds ratio [OR] 1.38, 95% CI: 0.80 to 2.38, p = 0.245) nor dyssynergic defecation and gastroparesis (OR 0.88, 95% CI: 0.29 to 2.70, p = 0.822). However, when stratifying gastroparesis based on severity, slow-transit constipation was found to be associated with severe gastroparesis (OR 2.45, 95% CI: 1.20 to 5.00, p = 0.014). This association was strengthened with the exclusion of patients with DM (OR 3.5, 95% CI: 1.39 to 8.83, p = 0.008) – a potential confounder. The authors concluded that patients with severe gastroparesis (greater than 35% gastric retention at the 4-hour mark on solid-phase GES) had an increased likelihood of having underlying slow-transit constipation. Moreover, dyssynergic defecation did not appear to be associated with gastroparesis (of any severity).
The authors stated that this study had several drawbacks. First, it was a retrospective review of patient data; thus, it could demonstrate an association between variables but did not imply causation. This patient population originated from a single, large, tertiary care center, which predisposed the study to a component of selection bias; therefore, limiting generalizability to an extent. In addition, a fraction (33%) of the total available patient population was selected for study inclusion, which could have introduced additional selection bias (although these investigators tried to minimize this via random sampling). Only a subset (58/224 [25.9%]) of the patients had anorectal manometry data available; thus, limiting the sample size of this particular population of patients. However, these findings of a lack of an association between gastroparesis and dyssynergic defecation were in agreement with a recent, larger-scale study (Zikos et al, 2019). With regards to the methodology/testing, GES and WMC testing were not carried out within the same patient visit; thus, it was possible that physiological changes in motility occurred in the time interval between these 2 evaluations. Finally, this trial did not examine if constipated patients experienced any improvement in symptoms or the rate of gastric emptying following the management of slow-transit constipation.
Sangnes et al (2021) stated that diabetic constipation is traditionally attributed to slow colonic transit, despite limited evidence. More than 50% of patients find treatment unsatisfactory. To improve treatment, there is a need for better diagnostic understanding of the condition. In a WMC study, these investigators examined GI transit and contractility in diabetes patients with and without constipation, and in healthy controls (HCs). They prospectively included type-I DM or type-II DM patients with GI symptoms. Based on the Gastrointestinal Symptom Rating Scale (GSRS), subjects were divided into 2 groups: with constipation and without constipation. Non-diabetic controls were asymptomatic. All were examined with WMC, determining transit times and contractility parameters. A total of 57 patients (42 women, 46 with type-I DM) and 26 HCs (14 women) were included. These investigators found no difference in transit times between diabetes patients with and without constipation. Compared to HCs (35:55, hrs:mins), whole-gut transit was slower in both diabetes patients with constipation (66:15, p = 0.03) and without constipation (71:16, p < 0.001). Small bowel motility index correlated (rs = -0.32 (p = 0.01) with constipation symptoms. The authors concluded that DM patients with constipation had similar transit times as those without constipation. Both groups had slower whole-gut transit than HCs. Constipation was associated with reduced small bowel, but not colonic contractility. These researchers stated that these findings may imply that DM patients with constipation need a more comprehensive diagnostic investigation than transit time studies, and that other factors may be more important in generating constipation symptoms in these patients.
The authors stated that this study was cross‐sectional and exploratory; therefore, it was not designed to examine causality. Despite this, these findings may have clinical significance. When so many patients with diabetic constipation experienced inadequate treatment, this may indicate that the diagnostics have not identified the causative mechanism behind the symptoms. Slow transit has for long been considered the main mechanism behind diabetic constipation, but other possible explanations have been sparsely examined. These investigators attempted to discuss some of these potential causes. Of these, evacuation disorders caused by diabetes‐induced damage to the neural regulation may be the most likely and merits further investigation. Furthermore, these researchers have shown that diabetes patients with constipation had higher anxiety levels. Chronic anxiety may further contribute to the development of rectal evacuation disorders. Most likely, diabetic constipation is a heterogeneous disorder; thus, these investigators emphasized the need for a thorough investigation before initiating treatment, which should be individualized based on diagnostic findings. Prokinetic agents may still have a place in treatment but other causes like rectal evacuation disorders and psychiatric co-morbidities should be ruled out first, as these require an entirely different approach to treatment than slow‐transit constipation. When performing GI motility testing, these findings also underlined the relevance of evaluating more than just colonic transit, as diabetes patients regularly show concurrent affection of multiple GI segments.
Additional drawbacks of this trial included the following: First, it was carried out at a tertiary center and most of the patients had type-I DM; thus, findings may not be representative for diabetic patients in the general population. Second, the sample size of the constipation group was also small, increasing the risk for type II errors. When performing multiple comparisons, as in this trial, there was a risk of type I errors. To control for this, these researchers employed the Games‐Howell and Bonferroni post-hoc tests when calculating results from normally and non‐normally distributed parameters, respectively. Third, as co-morbidities associated with constipation are frequent in diabetic patients, excluding these would potentially introduce a selection bias. Of ethical reasons, these investigators also advised patients to continue their regular medications, except those discouraged by the WMC protocol. Controlling for the effect of co-morbidities and medications, these researchers found no difference in constipation symptoms. Neither did they find any difference in thyroid function tests, fecal calprotectin and fecal elastase‐1. Due to the simultaneous investigation with scintigraphy, diabetic patients received a meal with 90 kcal higher caloric content than HCs. Although the authors could not exclude a minor influence on gastric emptying, they found it unlikely that colonic and whole‐gut transit results were affected. Fourth, the lack of a pre-defined cut‐off value is a limitation of the GSRS questionnaire. To control for this, these investigators conducted correlation analyses, without finding any association between constipation symptoms and transit times. Fifth, HCs were recruited as part of a collaborating study and included a lower proportion of women compared to diabetic patients with constipation; and HCs also trended towards a lower mean age. This may have introduced a bias due to gender differences in transit times. Finally, HCs did not answer the GSRS but were screened before inclusion using modified Rome III questionnaires and clinical interview.
Camilleri et al. (2022) on "ACG Clinical Guideline: Gastroparesis" provide the recommendation that wireless motility capsule may be an alternative to scintigraphic gastric emptying assessment for the evaluation of gastroparesis in patients with upper GI symptoms (conditional recommendation [i.e., the patient should receive the recommended course of action but different choices may be appropriate for some patients], low quality of evidence [i.e., further research very likely to have important impact on confidence in estimate of effect; estimate will likely change]).
The PillSense System for the Detection of Upper GI Bleeding
Schuster et al (2024) noted that upper GI bleeding (UGIB) is a life-threatening condition that necessitates early identification and intervention, and is associated with substantial morbidity, mortality, as well as socio-economic burden; however, several diagnostic challenges remain regarding risk stratification and the optimal timing of endoscopy. The PillSense System is a non-invasive device developed to detect blood in patients with UGIB in real time. In a pre-clinical study, these investigators examined the safety and performance characteristics of the PillSense System by means of a simulated bleeding model. This trial was carried out using an in-vivo porcine model (14 animals). A total of 14 PillSense capsules were endoscopically placed in the stomach; and blood was injected into the stomach to simulate bleeding. The safety and sensitivity of blood detection and pill excretion were also examined. All the sensors successfully detected the presence or absence of blood. The minimum threshold was 9% blood concentration, with additional detection of increasing concentrations of up to 22.5% blood. All the sensors passed naturally via the GI tract. The authors concluded that the findings of this study showed the ability of the PillSense System sensor to detect UGIB across a wide range of blood concentrations. This ingestible device detects UGIB in real time and has the potential to be an effective tool to supplement the current standard of care (SOC). Moreover, these researchers stated that these favorable findings will be further examined in prospective, human trials.
Akiki et al (2024) stated that UGIB is a common medical emergency associated with high resource utilization, morbidity, and mortality. Timely esophagogastroduodenoscopy (EGD) can be challenging from personnel, resource, and access perspectives. The PillSense System (EnteraSense Ltd, Galway, Ireland) is a novel, swallowed bleeding sensor for the detection of UGIB, designed to aid in triaging patient and guiding decision-making for individuals with suspected UGIB. In a prospective, open-label, single-arm, clinical trial, these researchers examined the safety and effectiveness of a novel bleeding sensing system for use in patients with suspected UGIB. The PillSense System consists of an optical sensor and an external receiver that processes and displays data from the capsule as "blood detected" or "no blood detected". Subjects underwent EGD within 4 hours of capsule administration; they were followed-up for 21 days to confirm capsule passage. A total of 126 patients were enrolled in this trial (59.5% men; mean age of 62.4 ± 14.3 years). Sensitivity and specificity for detecting the presence of blood were 92.9% (p = 0.02) and 90.6% (p < 0.001), respectively. The capsule's positive and negative predictive values (PPV and NPV) were 74.3% and 97.8%, and positive and negative likelihood ratios (PLR and NLR) were 9.9 and 0.08. No adverse events (AEs) or deaths occurred related to the PillSense System, and all capsules were excreted from patients on follow-up. The authors concluded that the PillSense System was safe and effective for detecting the presence of blood in patients evaluated for UGIB before upper GI endoscopy. It is a rapidly deployed tool, with easy-to-interpret results that may assist in efficiently diagnosing UGIB, with the objective of improving patient outcomes, and may ultimately alter the diagnostic and therapeutic approach for patients with a suspected UGIB.
The authors stated that the study design in a single, tertiary care center was a limiting factor, which may hinder generalizability of these findings. At the Mayo Clinic, a specialized GI bleeding team exists for rapid assessment and intervention in patients presenting with GI bleeding, a resource that may not be widely available at other institutions. Moreover, the primary objective of this study was to examine the sensitivity and specificity of the PillSense System in identifying UGIB in acute situations. This initial clinical trial was not designed to establish optimal clinical pathways for the use of the PillSense System. These researchers stated that further investigations are needed to identify and validate the performance of the PillSense System in a real-world clinical setting. Lasty, the study received funding from the manufacturer of the PillSense System. To mitigate potential sponsorship bias, these investigators maintained strict independence by granting full autonomy to the Principal Investigator. Proceduralists were blinded to PillSense results to enhance objectivity. These steps ensured research integrity.
In a review on "Novel upper gastrointestinal bleeding sensor capsule", Bajer et al (2024) noted that the PillSense System is a non-invasive device designed for the real-time detection of GI bleeding as liquid blood and/or hematin. The System consists of 2 components, a single-use, swallowable capsule containing an optical sensor that detects blood as it is propelled through the GI tract, and a wireless bedside receiver. The capsule is battery-powered, pill-shaped, and 11×27 mm in size. The capsule begins to gather data as soon as it is immersed in liquid. The visible light emitted by the capsule passes through the surrounding liquid, and the wavelengths detected by the sensor are analyzed by means of a proprietary algorithm. The resulting sensor output indicates the presence or absence of blood, and the wireless receiver displays a real-time continuous graph of the sensor output with numeric values ranging from 0 to 5. A cut-off value of 1.8 has been determined to indicate the presence (1.8 or higher) or absence (less than 1.8) of blood, and the receiver automatically reports a binary interpretation of the data, either "blood detected" or "no blood detected". Due to the binary output, the device is not currently designed to determine the amount or rate of the bleed.
In a commentary on the study by Bajer et al (2024), Lim (2024) stated that "[t]he system for real-time blood detection proposed in this study emerges as an appealing method for confirming the presence of UGIB compared to existing prediction systems. Although it is currently in the very early stages of development, technological improvements are expected, rendering it a valuable device for future clinical applications".
References
The above policy is based on the following references:
3D High-Resolution Manometry
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- Singendonk MMJ, Ferris LF, McCall L, et al; in association with the European Society for Pediatric Gastroenterology, Hepatology, Nutrition (ESPGHAN) Pediatric Motility Network. High-resolution esophageal manometry in pediatrics: Effect of esophageal length on diagnostic measures. Neurogastroenterol Motil. 2020;32(1):e13721.
Body Surface Gastric Mapping (Gastric Alimetry)
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- Calder S, Cheng LK, Andrews CN, et al. Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine. Am J Physiol Gastrointest Liver Physiol. 2022;323(4):G295-G305.
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- Gharibans AA, Coleman TP, Mousa H, Kunkel DC. Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis. Clin Gastroenterol Hepatol. 2019;17(13):2668-2677.
- Gharibans AA, Hayes TCL, Carson DA, et al. A novel scalable electrode array and system for non-invasively assessing gastric function using flexible electronics. Neurogastroenterol Motil. 2023;35(2):e14418.
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- Law M, Schamberg G, Gharibans A, et al. Short- and long-term reproducibility of body surface gastric mapping using the Gastric Alimetry® system. Neurogastroenterol Motil. 2024;36(7):e14812.
- Law M, Schamberg G, Varghese C, et al. Psychometric profiling of patients with chronic gastroduodenal symptoms using body surface gastric mapping phenotypes. medRxiv. Published July 29, 2025.
- Lim AH, Varghese C, Sebaratnam GH, et al. Effect of menstrual cycle and menopause on human gastric electrophysiology. Am J Physiol Gastrointest Liver Physiol. 2024;327(1):G47-G56.
- Lim AH, Varghese C, Sebaratnam G, et al. Nausea and Gastric Myoelectrical Activity Are Influenced by Hormonal Contraception in Chronic Gastroduodenal Disorders. Clin Transl Gastroenterol. 2025;16(9):e00880.
- Mori H. Early detection and intervention in diabetic gastroparesis: Role of body surface gastric mapping. World J Gastroenterol. 2024;30(45):4836-4838.
- O'Grady G, Varghese C, Schamberg G, et al; BSGM Working Group. Principles and clinical methods of body surface gastric mapping: Technical review. Neurogastroenterol Motil. 2023;35(10):e14556.
- Sadaka C, Xu B, Benitez AJ, et al. Neuropathic Gastroduodenal Disorders Can Be Diagnosed by Non-Invasive Body Surface Gastric Mapping: A Comparison With Antroduodenal Manometry. Neurogastroenterol Motil. 2025;37(10):e70087.
- Schamberg G, Calder S, Varghese C, et al. Comparison of Gastric Alimetry® body surface gastric mapping versus electrogastrography spectral analysis. Sci Rep. 2023;13(1):14987.
- Schamberg G, Varghese C, Calder S, et al. Revised spectral metrics for body surface measurements of gastric electrophysiology. Neurogastroenterol Motil. 2023;35(3):e14491.
- Sebaratnam G, Karulkar N, Calder S, et al. Standardized system and App for continuous patient symptom logging in gastroduodenal disorders: Design, implementation, and validation. Neurogastroenterol Motil. 2022;34(8):e14331.
- Seo SHB, Wells CI, Dickson T, et al. Validation of body surface colonic mapping (BSCM) against high resolution colonic manometry for evaluation of colonic motility. Sci Rep. 2024;14(1):4842.
- Shaaban H, Varghese C, Schamberg G, et al. Liquid nutrient drink testing induces gastric myoelectrical abnormalities that correlate with gastroduodenal symptoms. Am J Physiol Gastrointest Liver Physiol. 2025;329(3):G363-G370.
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- Varghese C, Huang IH, Schamberg G, et al. Distinct Subgroups in Gastroparesis Defined by Simultaneous Body Surface Gastric Mapping and Gastric Emptying Breath Testing. Neurogastroenterol Motil. 2025;37(11):e70124.
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- Varghese C, Schamberg G, Calder S, et al. Normative values for body surface gastric mapping evaluations of gastric motility using gastric alimetry: Spectral analysis. Am J Gastroenterol. 2023c;118(6):1047-1057.
- Varghese C, Schamberg G, Uren E, et al. A Standardized Classification Scheme for Gastroduodenal Disorder Evaluation Using the Gastric Alimetry System: Prospective Cohort Study. Gastro Hep Adv. 2025;4(1):100547.
- Varghese C, Van Hove S, Schamberg G, et al. Predicting Symptomatic Response to Prokinetic Treatment Using Gastric Alimetry. Neurogastroenterol Motil. 2025;37(11):e70132.
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- Varghese C, Zhou W, Gharibans A, Schamberg G, Van Hove S, O’Grady G, Neshatian L, Nguyen L. Autonomic Dysfunction in Gastroduodenal Disorders Evaluated through Multimodal Non-Invasive Physiological Testing. medRxiv. Published June 30, 2025.
- Wang WJ, Foong D, Calder S, et al. Gastric Alimetry® expands patient phenotyping in gastroduodenal disorders compared to gastric emptying scintigraphy. Am J Gastroenterol. 2024;119(2):331-341.
- Wang TH, Tokhi A, Gharibans A, et al. Non-invasive thoracoabdominal mapping of postoesophagectomy conduit function. BJS Open. 2023;7(3):zrad036.
- Wang TH, Varghese C, Calder S, et al. Assessment of Gastric Remnant Activity, Symptoms, and Quality of Life Following Gastric Bypass. Obes Surg. 2024;34(12):4490-4498.
- Wang TH-H, Varghese C, Calder S, Gharibans A, Schamberg G, Bartlett A, Srinivasa S, O’Grady G. Evaluation of gastric electrophysiology, symptoms and quality of life after pancreaticoduodenectomy. medRxiv. Published December 17, 2023.
- Wang TH, Varghese C, Robertson S, Beban G, Evennett N, Foong D, et al. Abnormal gastric electrophysiology following laparoscopic sleeve gastrectomy and associations with symptoms and quality of life. medRxiv. Published March 11, 2025.
- Xu W, Gharibans AA, Calder S, et al. Defining and phenotyping gastric abnormalities in long-term type 1 diabetes using body surface gastric mapping. Gastro Hep Advances. 2023;2(8):1120-1132.
- Xu W, Simmonds S, Foong D, et al. Association between gastric rhythm and gastroesophageal reflux defined by simultaneous body surface gastric mapping and 24-hour pH testing. medRxiv. Published July 28, 2025.
- Xu W, Wang T, Foong D, et al. Characterization of gastric dysfunction after fundoplication using body surface gastric mapping. J Gastrointest Surg. 2024;28(3):236-245.
- Xu W, Williams L, Sebaratnam G, et al. Gastric Alimetry Testing and healthcare economic analysis in nausea and vomiting syndromes. Dig Dis Sci. 2024;69(7):2304-2314.
Colonic Motility Studies
- Altomare DF, Portincasa P, Rinaldi M, et al. Slow-transit constipation: Solitary symptom of a systemic gastrointestinal disease. Dis Colon Rectum. 1999;42(2):231-240.
- American Gastroenterological Association (AGA). American Gastroenterological Association medical position statement: Nausea and vomiting. Gastroenterology. 2001;120(1): 261-263.
- Arbizu RA, Nurko S, Heinz N, et al. Prospective evaluation of same day versus next day colon manometry results in children with medical refractory constipation. Neurogastroenterol Motil. 2017;29(7).
- Bassotti G, Crowell MD, Cheskin LJ, et al. Physiological correlates of colonic motility in patients with irritable bowel syndrome. Z Gastroenterol. 1998;36(9):811-817.
- Bassotti G, de Roberto G, Chistolini F, et al. Twenty-four-hour manometric study of colonic propulsive activity in patients with diarrhea due to inflammatory (ulcerative colitis) and non-inflammatory (irritable bowel syndrome) conditions. Int J Colorectal Dis. 2004;19(5):493-497.
- Bassotti G, Iantorno G, Fiorella S, et al. Colonic motility in man: Features in normal subjects and in patients with chronic idiopathic constipation. Am J Gastroenterol. 1999;94(7):1760-1770.
- Brown AJ, Nicol L, Anderson JH, et al. Prospective study of the effect of rectopexy on colonic motility in patients with rectal prolapse. Br J Surg. 2005;92(11):1417-1422.
- Camilleri M, Ford MJ. Review article: Colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders. Aliment Pharmacol Ther. 1998;12(4):287-302.
- Camilleri M. Motor function in irritable bowel syndrome. Can J Gastroenterol. 1999;13(Suppl A):8A-11A.
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- Dinning PG, Carrington EV, Scott SM. Colonic and anorectal motility testing in the high-resolution era. Curr Opin Gastroenterol. 2016;32(1):44-48.
- Drossman DA. Review article: An integrated approach to the irritable bowel syndrome. Aliment Pharmacol Ther. 1999;13(Suppl 2):3-14.
- El-Chammas KI, Tipnis NA, Simpson PM, Sood MR. Colon high-resolution manometry: Using pressure topography plots to evaluate pediatric colon motility. J Pediatr Gastroenterol Nutr. 2014;59(4):500-504.
- Ghoshal UC, Gupta D, Kumar A, Misra A. Colonic transit study by radio-opaque markers to investigate constipation: Validation of a new protocol for a population with rapid gut transit. Natl Med J India. 2007;20(5):225-229.
- Herbst F, Kamm MA, Morris GP, et al. Gastrointestinal transit and prolonged ambulatory colonic motility in health and faecal incontinence. Gut. 1997;41(3):381-389.
- Jaung R, Robertson J, O'Grady G, et al. Limited evidence of abnormal intra-colonic pressure profiles in diverticular disease - a systematic review. Colorectal Dis. 2017;19(6):O168-O176.
- Liem O, Burgers RE, Connor FL, et al. Prolonged colonic manometry in children with defecatory disorders. J Pediatr Gastroenterol Nutr. 2014;59(6):748-753.
- Locke GR, Pemberton JH, Phillips SF. American Gastroenterological Association medical position statement: Guidelines on constipation. Gastroenterology. 2000;119(6):1761-1766.
- Mugie SM, Perez ME, Burgers R, et al. Colonic manometry and colonic scintigraphy as a diagnostic tool for children with severe constipation. J Pediatr Gastroenterol Nutr. 2013;57(5):598-602.
- Paterson WG, Thompson WG, Vanner SJ, et al. Recommendations for the management of irritable bowel syndrome in family practice. IBS Consensus Conference Participants. CMAJ. 1999;161(2):154-160.
- Penchev P, Noeva A, Zlatarsky G, et al. Non-invasive electrocologram: Non-invasive recording of the human colonic electrical activity. Acta Physiol Pharmacol Bulg. 1996;22(3-4):83-88.
- Rao SS, Camilleri M, Hasler WL, et al. Evaluation of gastrointestinal transit in clinical practice: Position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterol Motil. 2011;23(1):8-23.
- Rao SS, Sadeghi P, Beaty J, Kavlock R. Ambulatory 24-hour colonic manometry in slow-transit constipation. Am J Gastroenterol. 2004;99(12):2405-2416.
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- Smout AJ, Mundt MW. Gastrointestinal motility testing. Best Pract Res Clin Gastroenterol. 2009;23(3):287-298.
- Soffer EE. Constipation: An approach to diagnosis, treatment, referral. Cleve Clin J Med. 1999;66(1):41-46.
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- Tanaka Y, Kanazawa M, Palsson OS, et al. Increased postprandial colonic motility and autonomic nervous system activity in patients with irritable bowel syndrome: A prospective study. J Neurogastroenterol Motil. 2018;24(1):87-95.
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Electrogastrography
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- Camilleri M, Hasler WL, Parkman HP, et al. Measurement of gastrointestinal motility in the GI laboratory. Gastroenterology. 1998;115(3):747-762.
- Chen CL, Hu CT, Lin HH, Yi CH. Clinical utility of electrogastrography and the water load test in patients with upper gastrointestinal symptoms. J Smooth Muscle Res. 2006;42(5):149-157.
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Gastric Emptying Breath Testing (GEBT)
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- Sangnes DA, Softeland E, Teigland T, et al. Comparing radiopaque markers and 13C-labelled breath test in diabetic gastroparesis. Clin Exp Gastroenterol. 2019;12:193-201.
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Helicobacter Pylori Infection -- A Risk Factor for Irritable Bowel Syndrome
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High Resolution Esophageal Pressure Topography (HREPT)
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Immunoglobulin G Antibody Test for Food Triggers Associated with Irritable Bowel Syndrome
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Radionuclide Gastric Emptying Study
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- Maurer AH, Camilleri M, Donohoe K, et al. The SNMMI and EANM practice guideline for small-bowel and colon transit 1.0. J Nucl Med. 2013;54(11):2004-2013.
- Maurer AH, Parkman HP. Update on gastrointestinal scintigraphy. Semin Nucl Med. 2006;36(2):110-118.
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- Smith DS, Ferris CD. Current concepts in diabetic gastroparesis. Drugs. 2003;63(13):1339-1358.
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Wireless Capsule for Measuring Gastric Emptying (SmartPill GI Monitoring System)
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- Agency for Healthcare Research and Quality (AHRQ). Smartpill Wireless Motility Capsule. Nomination Summary Document. Topic 0312. Rockville, MD: AHRQ; January 18, 2011.
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- BlueCross BlueShield Association (BCBSA), Technology Evaluation Center (TEC). Wireless motility capsule in the diagnosis and evaluation of gastroparesis or slow-transit constipation. TEC Assessment Program. Chicago, IL: BCBSA; October 2012;27(4).
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- Camilleri M, Kuo B, Nguyen L, et al. ACG Clinical Guideline: Gastroparesis. Am J Gastroenterol. 2022;117(8):1197-1220.
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- Camilleri M, Thorne NK, Ringel Y, et al. Wireless pH-motility capsule for colonic transit: Prospective comparison with radiopaque markers in chronic constipation. Neurogastroenterol Motil. 2010;22(8):874-882.
- 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(4):311-319.
- Diaz Tartera HO, Webb DL, Al-Saffar AK, et al. Validation of SmartPill® wireless motility capsule for gastrointestinal transit time: Intra-subject variability, software accuracy and comparison with video capsule endoscopy. Neurogastroenterol Motil. 2017;29(10):1-9.
- Hasler WL. The use of SmartPill for gastric monitoring. Expert Rev Gastroenterol Hepatol. 2014;8(6):587-600.
- Kloetzer L, Chey W, McCallum R, et al. Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule. Neurogastroenterol Motil. 2010;22(5):527-533.
- Koziolek M, Grimm M, Bollmann T, et al. Characterization of the GI transit conditions in Beagle dogs with a telemetric motility capsule. Eur J Pharm Biopharm. 2019;136:221-230.
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- Kuo B, McCallum R, Kock K, et al. Smartpill, a novel ambulatory diagnostic test for measuring gastric emptying in healthy and disease. Gastroenterology. 2006;130:A-434.
- Kuo B, McCallum RW, Kock KL, et al. Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects. Aliment Pharmacol Ther. 2008;27(2):186-196.
- 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(10):2167-2174.
- Paquette IM, Varma M, Ternent C, et al. The American Society of Colon and Rectal Surgeons' Clinical Practice Guideline for the evaluation and management of constipation. Dis Colon Rectum. 2016;59(6):479-492.
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- Radetic M, Kamal A, Rouphael C, et al. Severe gastroparesis is associated with an increased incidence of slow-transit constipation as measured by wireless motility capsule. Neurogastroenterol Motil. 2021;33(5):e14045.
- Rao SS, Kuo B, McCallum RW, et al. Investigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol. 2009;7(5):537-544.
- Rao SSC, Mysore K, Attaluri A, Valestin J. Diagnostic utility of wireless motility capsule in gastrointestinal dysmotility. J Clin Gastroenterol. 2011;45(8):684-690.
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- Saad RJ, Hasler WL. A technical review and clinical assessment of the wireless motility capsule. Gastroenterol Hepatol (N Y). 2011;7(12):795-804.
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- Sarosiek I, Selover K, Semler L, et al. The assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology. Aliment Pharmacol Ther. 2010;31(2):312-322.
- SmartPill Corporation. SmartPill wins 510(k) release from FDA. The SmartPill GI Monitoring System will be available to GI professionals this fall. News Release. Buffalo, NY: SmartPill Corporation; July 20, 2006.
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- Willis HJ, Thomas W, Willis DJ, Slavin JL. Feasibility of measuring gastric emptying time, with a wireless motility device, after subjects consume fiber-matched liquid and solid breakfasts. Appetite. 2011;57(1):38-44.
- Yung D, Douglas S, Hobson AR, et al. Morpho-functional evaluation of small bowel using wireless motility capsule and video capsule endoscopy in patients with known or suspected Crohn's disease: Pilot study. Endosc Int Open. 2016;4(4):E480-E486.
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The PillSense System for the Detection of Upper GI Bleeding
- Akiki K, Mahmoud T, Alqaisieh MH, et al. A novel blood-sensing capsule for rapid detection of upper GI bleeding: A prospective clinical trial. Gastrointest Endosc. 2024;99(5):712-720.
- Bajer L, Ryou M, Thompson CC, Drastich P. Novel upper gastrointestinal bleeding sensor capsule: A first human feasibility and safety trial. Clin Endosc. 2024;57(2):203-208.
- Lim SG. Could a bleeding-sensor device be established as a new paradigm for detecting upper gastrointestinal bleeding before performing endoscopy? Clin Endosc. 2024;57(2):191-192.
- Schuster KF, Thompson CC, Ryou M. Preclinical study of a novel ingestible bleeding sensor for upper gastrointestinal bleeding. Clin Endosc. 2024;57(1):73-81.
