Wireless Motility Capsule Testing Research Articles

The Association Between Acidification Time on Wireless Motility Capsule and Gastroesophageal Reflux Disease.

Gastric physiological characteristics such as fundus accommodation, gastric distention, emptying/transit time, and basal acid output may contribute to the pathogenesis of gastroesophageal reflux disease (GERD). Wireless motility capsule (WMC) uses pH data to determine gastric transit time but has not been used in the evaluation of GERD. Certain metrics such as acidification time, nadir pH, and gastric transit time may provide insight into the mechanisms of GERD related to gastric physiology, allowing WMC to be a complementary tool in the diagnosis of GERD. We aimed to determine whether pH data and transit time on WMC tests correlated with the presence of GERD on ambulatory reflux testing. This was a retrospective study of 28 patients who had undergone both WMC and reflux testing via wireless pH or pH/impedance. Acidification time (time from capsule ingestion to pH<2), nadir postprandial pH, and gastric transit time were manually determined from the WMC capsule proprietary software. Spearman correlation was used to compare these metrics with gastric transit time, percent esophageal acid exposure, and DeMeester score. Acidification time moderately correlated with gastric transit time, R: 0.44, P=0.02, but not nadir pH, percent esophageal acid exposure, or DeMeester score. Patients with an abnormal reflux test had a significantly longer median acidification time (135.5 vs. 78.5min, P=0.021). After stratifying by patients with normal versus prolonged gastric transit time, there was a trend toward longer acidification time in patients with positive reflux testing in both groups, but this was not statistically significant. Patients with prolonged gastric transit time >300 minutes were not more likely to have a positive reflux test (38% vs. 35%, P=1). The acidification time on WMC was significantly longer in patients with proven GERD and acidification time positively correlated with gastric transit time. Larger studies are needed to determine whether WMC could be used as a complementary tool in investigating patients with GERD symptoms.

Gastrointestinal Sensory Neuropathy and Dysmotility in Fabry Disease: Presentations and Effect on Patient's Quality of Life.

Fabry disease is a rare multisystemic lysosomal disease resulting in variable manifestations of the gastrointestinal (GI), neurologic, cardiac, and renal systems. Whether GI manifestations are a result of gut dysmotility is undetermined. We aimed to explore GI manifestations in depth and their effect on patients with Fabry disease and to characterize gut motility. We recruited adult patients with Fabry disease reporting GI manifestations. All patients answered a battery of questionnaires covering symptom severity, GI-specific quality of life, and effects of work/productivity and underwent a wireless motility capsule test to measure pan-gut motility. In 48 patients with Fabry disease, abnormal bowel habits and abdominal pain were the most common symptoms. Bloating, nausea, vomiting, and reflux were also prevalent. Neurologic manifestations were found in 95.8% of patients, along with their GI manifestations. Dysmotility was found in less than 35% of wireless motility capsule tests. Colon transit time was associated with constipation severity and Bristol Stool Scale. Several GI symptoms were associated with reduced quality of life, anxiety, and work/productivity, but not Fabry severity score. This is the largest study of GI manifestations in patients with Fabry disease that characterizes gut motility. We found little association between GI manifestations and motility indices, suggesting that visceral hypersensitivity may be a major driver of symptoms. GI symptoms affect different aspects of patients' lives, yet are not always well-discussed or optimally managed in Fabry disease. Disease severity scores when used for therapeutic decision making do not often include GI symptoms or their impact.

Quantitative gastrointestinal function and corresponding symptom profiles in autonomic neuropathy.

Peripheral neuropathies with autonomic nervous system involvement are a recognized cause of gastrointestinal dysmotility for a wide spectrum of diseases. Recent advances in wireless motility capsule testing allow improved sampling of regional and whole gut motility to aid in the diagnosis of gastrointestinal motility disorders and may provide additional insight into segment-specific enteric involvement of peripheral neuropathies affecting autonomic nervous system function. We utilized standardized autonomic nervous system (ANS) reflex assessment and wireless motility capsule testing to evaluate 20 individuals with idiopathic autonomic neuropathy and unexplained gastrointestinal symptoms. Additionally, we examined the relationship between quantifiable autonomic neuropathy and gastrointestinal dysmotility at specific neuroanatomical levels. Symptom profiles were evaluated using the 31-item Composite Autonomic Symptom Score questionnaire (COMPASS-31) and compared to wireless motility capsule data. We found that transit times were predominately abnormal (delayed) in the foregut (10 of 20; 50%), while contractility abnormalities were far more prominent in the hindgut (17 of 20; 85%), and that motility and symptom patterns, as assessed by the COMPASS-31 GI domain items, generally corresponded. Finally, we also found that there was neuroanatomical overlap in the presence of autonomic reflex abnormalities and WMC-based transit and/or contractility abnormalities. We found that transit times were predominately abnormal in the foregut and midgut, while contractility abnormalities were far more prominent in the hindgut in individuals with idiopathic autonomic neuropathy. There was a high rate of agreement in segmental wireless motility capsule data with neuroanatomically corresponding standardized ANS function measures (e.g., cardiovagal, sudomotor, adrenergic). Expanded sudomotor testing, including additional neuroanatomical segments, could provide additional indirect assessment of visceral involvement in ANS dysfunction.

Impact of Objective Colonic and Whole Gut Motility Data as Measured by Wireless Motility Capsule on Outcomes of Antireflux Surgery.

Studies show higher rates of dissatisfaction with antireflux surgery (ARS) outcomes in patients with chronic constipation. This suggests a relationship between colonic dysmotility and suboptimal surgical outcome. However, due to limitations in technology, there is no objective data available examining this relationship. The wireless motility capsule (WMC) is a novel technology consisting of an ingestible capsule equipped with pH, temperature, and pressure sensors, which provide information regarding regional and whole gut transit times, pH and motility. The aim of this study was to assess the impact of objective regional and whole gut motility data on the outcomes of ARS. This was a retrospective review of patients who underwent WMC testing before ARS. Transit times, motility, and pH data obtained from different gastrointestinal tract regions were used in analysis to determine factors that impact surgical outcome. A favorable outcome was defined as complete resolution of the predominant reflux symptom and freedom from antisecretory medications. The final study population consisted of 48 patients (fundoplication [n = 29] and magnetic sphincter augmentation [n = 19]). Of those patients, 87.5% were females and the mean age ± SD was 51.8 ± 14.5 years. At follow-up (mean ± SD, 16.8 ± 13.2 months), 87.5% of all patients achieved favorable outcomes. Patients with unfavorable outcomes had longer mean whole gut transit times (92.0 hours vs 55.7 hours; p = 0.024) and colonic transit times (78.6 hours vs 47.3 hours; p = 0.028), higher mean peak colonic pH (8.8 vs 8.15; p = 0.009), and higher mean antral motility indexes (310 vs 90.1; p = 0.050). This is the first study to demonstrate that objective colonic dysmotility leads to suboptimal outcomes after ARS. WMC testing can assist with preoperative risk assessment and counseling for patients seeking ARS.

What Is Wrong With This Wireless Motility Capsule?

CASE REPORT A 37-year-old woman was evaluated for suspected gastroparesis with nausea, heartburn, and constipation. She reported bowel movements every 2 weeks (Bristol Stool Scale Type I–III) with excessive straining. She was taking pantoprazole, famotidine, promethazine, and bisacodyl. Her history included esophageal stricture requiring dilation 3 years previously. She reported intermittent dysphagia for solids. A wireless motility capsule (WMC) study was performed for the evaluation of gastrointestinal motility disorder. The WMC profile is presented (Figure 1). The horizontal axis shows the time scale, and the vertical axis shows pressure (red), pH (green), and temperature (blue). The pH was 5–7 with occasional decreases to 2.0 coinciding with drinks/meals, indicating esophageal capsule retention. Ten hours later, the patient vomited and expelled the capsule, confirmed by a temperature decline. A week later, an upper endoscopy confirmed distal esophageal stricture with mucosal changes of esophagitis (Figure 1). Pantoprazole was increased to twice daily, and repeat esophagogastroduodenoscopy in 8 weeks was recommended (Figure 2).Figure 1.: Wireless motility capsule profile of the patients. The horizontal axis shows the time scale, and the vertical axis shows pressure (red), pH (green), and temperature (blue). The pH was 5–7 with occasional decreases to 2.0 coinciding with drinks/meals, indicating esophageal capsule retention. Ten hours later, the patient vomited and expelled the capsule, confirmed by a temperature decline.Figure 2.: Upper endoscopy 1 week after wireless motility capsule testing confirming distal esophageal stricture with mucosal changes of esophagitis.The WMC study is contraindicated in patients with dysphagia, stricture, or bowel obstruction. Capsule retention, although rare (0.33%), can occur, especially if the contraindications for this test are not carefully ruled out before ordering the test.1 The test was incorrectly requested for the patient presented here, but fortunately, the patient vomited the capsule. In patients with dysphagia, stricture, or bowel obstruction, gastrointestinal dysmotility symptoms should be evaluated using alternative tests, such as scintigraphy. Although WMC is significant advance and clinically useful for the diagnosis of gastrointestinal motility disorders, the manufacturer's recommendations and precautions should be followed carefully to prevent potentially serious complications.2 DISCLOSURES Author contributions: L. Mosley wrote the manuscript. A. Jehangir edited the manuscript. S. Sridhar, A. Sharma, and S.S.C. Rao revised the manuscript for intellectual content. S.S.C. Rao is the article guarantor. All authors approve the final version of the manuscript. Financial disclosure: None to report. Previous presentation: This case was presented at the American College of Gastroenterology Annual Scientific Meeting; October 22–27, 2021; Las Vegas, Nevada. Informed consent was obtained for this case report.

Assessment of whole gut motility in adolescents using the wireless motility capsule test

Functional gastrointestinal (GI) disorders are often associated with intestinal dysmotility representing a diagnostic challenge. A relatively new method is the wireless motility capsule (WMC) test, which continuously measures pH, pressure, temperature and regional transit times as it passes through the GI tract. In adults, the WMC test was approved for use in the diagnosis of gastroparesis and constipation by assessing GI transit and contractility. We performed the WMC test in nine adolescent patients aged 12–17 years with functional GI symptoms from July 2017 until February 2019. Abnormal transit times were detected in four patients. Three patients showed abnormal transit times of the upper GI tract: in two cases, contractility analysis revealed prolonged gastric retention, and in one patient, abnormal colonic transit was detected.Conclusion: The WMC test is a minimally invasive procedure with potential to expand future diagnostic opportunities for paediatric patients with functional GI disorders and suspected motility disturbances.What is Known:• The assessment of GI transit and contractility of the whole gut is possible with the WMC test which is approved for use in the diagnosis of gastroparesis and constipation in adults. What is New:• The WMC test is a non-invasive diagnostic tool with the potential to expand diagnostic opportunities in paediatric patients by assessing regional and whole gut motility.• In paediatric patients with functional GI disorders, the WMC test could help to make an adequate diagnosis and initiate appropriate therapy.

Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain.

Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit. Thirty children ages 7-12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, 180 mg twice or 180 mg thrice daily) for 1 week during which time the WMC test was repeated. Evaluable area under the plasma concentration vs. time curve (AUClast ) data were available in 29 of 30 participants. A direct linear relationship (apparent dose-proportionality for systemic menthol exposure) was observed between PMO dose and menthol systemic exposure with mean elimination half-life 2.1, 3.5 and 4.6hours for the 180, 360 and 540 mg doses, respectively. WMC technical issues precluded complete motility data in all participants. Colonic transit time was inversely related to AUClast (P =.003); transit time in other regions was not affected. In contrast, stomach, small bowel and whole gut (but not colonic) contractility positively correlated with menthol AUClast (P <.05). Pharmacokinetics and pharmacodynamics of menthol derived from PMO demonstrated apparent dose-proportionality. A higher dose of PMO may be needed to achieve maximal gut response. www.clinicaltrials.gov NCT03295747.

Symptomatic gastrointestinal dysmotility in autonomic neuropathy

Autonomic neuropathy (AN) patients frequently experience multi-systemic symptoms, ranging from cardiovascular, urinary, secretory, and gastrointestinal (GI). Further, there is marked heterogeneity among patients, often limiting the yield of conventional diagnostic evaluations. The aim of this study was to describe our single-institution experience with wireless motility capsule (WMC) testing to quantitatively evaluate segmental dysfunction in AN patients with GI symptoms.

Gastrointestinal Physiology Before and After Duodenal Switch with Comparisons to Unoperated Lean Controls: Novel Use of the SmartPill Wireless Motility Capsule

PurposeBariatric surgery alters gastrointestinal anatomy. In this exploratory study, the SmartPill® wireless motility capsule (WMC) was used to study changes in gastrointestinal physiology following biliopancreatic diversion with duodenal switch (BPD/DS).Material and MethodsTwenty-eight BPD/DS patients (35 ± 11 years, 50% females, body mass index [BMI] 56 ± 5) were to be examined preoperatively and postoperatively. In addition to transit time, appetite control and gastrointestinal symptoms were studied by patient-scored questionnaires (visual analogue scale and Gastrointestinal Symptom Rating Scale (GSRS)). Data was compared to 41 lean unoperated controls.ResultsAbout 1.8 years postoperatively, 18 patients (BMI 35.8 ± 8.3) returned for a second WMC test. As expected, small bowel transit time was reduced, from 3.9 ± 1.6 h to 2.8 ± 2.0, p = 0.02, and at both these time points, it was shorter than in lean controls (5.4 ± 1.9 h, p = 0.001). Postoperatively, a trend towards reduced colon and whole gut transit times was seen in BPD/DS-patients, thus approaching those of lean controls. Surprisingly, BPD/DS patients scored higher satiety than controls preoperatively as well as increased hunger and desire to eat postoperatively. Compared to lean, BPD/DS patients reported a higher total GSRS score at both time points (1.2 ± 0.2 vs 1.7 ± 0.6 and 2.3 ± 0.5, p < 0.001). Postoperatively, the scores for diarrhea and indigestion increased.ConclusionsThe novel use of the SmartPill system in BPD/DS patients gave the expected readouts. Although small bowel transit time was further shortened after BPD/DS, whole gut transit time did not differ from controls. Typical gastrointestinal symptoms were reported postoperatively.Graphical abstract

Auxiliary Tests of Autonomic Functions.

The autonomic nervous system is a complex neural network that controls several organ systems. Its assessment includes a detailed history of autonomic functions, clinical examination, and autonomic tests. Most widely used is a battery of tests that assess cardiovascular reflex autonomic and sudomotor tests, which include deep breathing (assesses parasympathetic function), Valsalva maneuver, tilt test (both assess parasympathetic and adrenergic functions), and sudomotor testing for the evaluation of postganglionic sudomotor fibers. These basic tests represent a foundation of autonomic testing. Nevertheless, the autonomic nervous system also controls organ systems not directly assessed by basic tests. This review describes a number of auxiliary autonomic tests that can be used in addition to basic autonomic tests or can be used independently to explore particular autonomic functions or to answer a specific clinical question. The auxiliary tests described in this review evaluate cardiovascular, thermoregulatory, gastrointestinal, genitourinary, eye, and exocrine functions. These tests are cold pressor test, sustained handgrip maneuver, reverse tilt test, venoarteriolar reflex, laser Doppler flare imaging, microneurography, neck suction, lower body negative pressure, venous occlusion plethysmography, pharmacologic assessment of postganglionic sympathetic outflow, plasma norepinephrine, sympathetic skin response, video cinefluoroscopic swallowing test, esophageal manometry test, small bowel manometry test, wireless motility capsule test, urodynamic studies, penile plethysmography, intracavernosal papaverine injection, infrared video pupillography, corneal confocal microscopy, pupillary response to dilute pilocarpine and hydroxyamphetamine, Schirmer test, tear osmolarity test, and salivary secretion test. The protocol of each test is described in detail. This review can be used as a quick reference for the auxiliary autonomic tests.

Severe gastroparesis is associated with an increased incidence of slow-transit constipation as measured by wireless motility capsule.

Dysmotility in one region of the gastrointestinal tract has been found to predispose patients to developing motility disorders in other gastrointestinal segments. However, few studies have evaluated the relationship between gastroparesis and constipation. Retrospective review of 224 patients who completed 4-hour, solid-phase gastric emptying scintigraphy (GES), and wireless motility capsule (WMC) testing to evaluate for gastroparesis and slow-transit constipation, respectively. When available, anorectal manometry data were reviewed to evaluate for dyssynergic defecation. Patients were divided into two 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% vs 34.7%, p=0.304). Univariate logistical regression analysis found no association between slow-transit constipation and gastroparesis (OR 1.38, 95% CI 0.80-2.38, p=0.245) nor dyssynergic defecation and gastroparesis (OR 0.88, 95% CI 0.29-2.70, 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 1.20-5.00, p=0.014). This association was strengthened with the exclusion of patients with diabetes mellitus (OR 3.5, 95% CI 1.39-8.83, p=0.008) - a potential confounder. Patients with severe gastroparesis (>35% gastric retention at the 4-hour mark on solid-phase GES) have an increased likelihood of having underlying slow-transit constipation. Dyssynergic defecation does not appear to be associated with gastroparesis (of any severity).

1217 Gastroparesis Dietary Recommendations in Patients With Gastroparesis-Like Symptoms Are Only Effective in Normal Colon Transit Documented by Wireless Motility Capsule Methodology

INTRODUCTION: We previously reported a positive impact of gastroparesis diet recommendations on overall and individual symptoms in patients with suspected gastroparesis who show gastric emptying delays. In contrast, those with non-delayed gastric emptying showed only minimal benefits on this diet. The impact of gastroparesis diet recommendations in patients with delayed colon transit (DCT) based on Wireless Motility Capsule (WMC) testing has not been assessed. We hypothesized that patients with normal colon transit (NCT) presenting with upper GI symptoms respond to a gastroparesis diet while those with DCT do not respond. METHODS: Patients with suspected gastroparesis at 10 tertiary centers underwent concurrent WMC testing and gastric emptying scintigraphy. Several treatment recommendations, including a gastroparesis diet (low fat, low fiber and low residue diet with small-sized but frequent meals) were recommended for 31 patients with NCT and 15 with DCT. For this analysis, overall GCSI, and individual symptom scores from PAGI-SYM surveys (0 = none, 5 = very severe) at baseline and 6- month follow-up on the gastroparesis diet were related to the presence or absence of DCT defined as colon transit exceeding 59 hours by WMC. RESULTS: Gastroparesis diet recommendations were associated with overall GCSI and PAGI-SYM score reductions from 2.6 ± 1.1 to 2.1 ± 1.1 (P = 0.004) and 2.5 ± 1.1 to 1.9 ± 1.2 (P = 0.0004), respectively, in patients with NCT. Individual symptoms of bloating, fullness and diarrhea also improved with NCT (P &lt; 0.02 for all) (Table 1). Constipation and lower abdominal pain scores did not differ pre- and post- gastroparesis diet recommendations. In patients with DCT, only constipation improved over 6 months (P = 0.04). This finding may be explained by increased use of laxatives in this group after DCT was found on WMC testing. CONCLUSION: This is the first study to show a differential impact of gastroparesis diet recommendations in patients with suspected gastroparesis based on colon transit findings by wireless motility capsules. A positive impact of the gastroparesis diet with long-term benefits on overall and individual symptoms up to 6 months in patients with suspected gastroparesis and normal colonic transit was seen. In contrast, patients with delayed colon transit had lesser benefits from gastroparesis diets. Whole gut transit testing with WMC may differentiate responders and non-responders to the gastroparesis diet based on colonic transit times.

481 Motility Abnormalities Identified by Wireless Motility Capsule in Postural Orthostatic Tachycardia Syndrome

INTRODUCTION: Gastrointestinal symptoms are common in patients with postural tachycardia syndrome (POTS). Previous studies have reported a wide range of abnormalities, particularly delayed gastric emptying in POTS. Wireless motility capsule (WMC) is a minimally invasive test that allows the evaluation of gastrointestinal physiology. We aimed to investigate the diagnostic yield of WMC in patients with POTS. METHODS: We conducted a retrospective review of all patients at our institution with both formal WMC testing (SmartpillTM) and autonomic testing for evaluation of gastrointestinal and neurological symptoms respectively. Patient demographics and results of respective testing were extracted. We compared transit abnormalities and contraction patterns between patients meeting diagnostic criteria for POTS and those without POTS. Transit abnormality percentages were compared using chi2 testing, and contraction pattern parameters were compared using 2-sample t-testing. RESULTS: A total of 27 women with both WMC and autonomic testing were studied. The mean age was 39.6 (range 18-68). Fourteen patients had POTS, while the other 13 had either mild or no autonomic abnormalities. Patients with POTS were more likely to have delayed small bowel transit (42.9% vs 7.69%, P = 0.037), but no differences were seen in gastric or colonic transit delays (Table 1). Additionally, POTS patients were more likely to exhibit a hypocontractile pattern throughout the gastrointestinal tract compared to non-POTS patients. Specifically, maximal gastric pressure, and small bowel peak amplitude and motility index were significantly lower in POTS patients. There was a trend towards lower colonic maximum pressure, contraction/min and peak amplitude in POTS patients that did not reach significance (Table 1). CONCLUSION: Our data shows that gastrointestinal motility abnormalities, as observed in WMC, are more common in patients with POTS. Patients with POTS were more likely to have delayed small bowel transit, as well as hypocontractile gastrointestinal patterns, particularly in the small bowel, compared to non-POTS patients. WMC offers a unique opportunity to evaluate patients with autonomic dysfunction and POTS. Further prospective evaluation and higher sample sizes are needed.

491 Wireless Motility Capsule Testing Results in New Diagnostic Information in 38% of Patients With Suspected GI Dysmotility: A 6-Year Review

INTRODUCTION: GI motility disturbances often present with upper and lower GI symptoms or a combination of both. Wireless Motility Capsule (WMC) is a standardized pH based test that can measure regional and whole gut actual transit times. Aims: 1. Determine the prevalence of transit time abnormalities in patients with GI dysmotility symptoms. 2. Correlate regional transit abnormality with clinical symptoms. 3. Assess change in patients' diagnosis based on WMC testing. METHODS: A prospective study of patients with suspected GI dysmotility who underwent WMC testing between 2012 and 2018. Patients were placed into three groups: 1) Upper GI symptoms: nausea, vomiting, bloating, and abdominal pain. 2) Lower GI symptoms: constipation and diarrhea. 3) Both upper and lower GI symptoms. Assessments of gastric emptying time (GET), small bowel transit time (SBTT), and colonic transit time (CTT) were recorded in each group and the diagnostic yield was evaluated. RESULTS: 72 patients were evaluated with WMC. 59 patients had complete study data and were included in the analysis. Mean age was 46 ± 14 years. 62 (86 %) were female. 21 (29%) had a h/o cancer. 22 (31%) were diabetic. 43/59 (73%) patients had an abnormal WMC result (Table 1). In patients with upper GI symptoms (n = 31), 15 (48%) had delayed GET (Table 2). New diagnostic information was obtained in 14/31 (45%). Of the 13 patients with lower GI symptoms, only 3 (23%) had a prolonged CTT. No patients had isolated abnormality of GET or SBTT. New diagnostic information was obtained in 5/13 (38%). In the group with overlapping upper and lower GI symptoms, only 2 (13%) had multiregional dysmotility. 8/15 (53%) patients had normal transit studies. This resulted in 5 patients (33%) with new diagnostic information. CONCLUSION: GI symptoms are not an accurate predictor of disease localization. Only15 (48%) of the patients with upper GI symptoms had gastroparesis, and 3 (23%) of the patients with lower GI symptoms had slow transit constipation. WMC study resulted in new diagnostic information in 45% of patients with upper GI symptoms, 38% of patients with lower GI symptoms and 33 % of patients with pan GI symptoms, including the presence of isolated and whole gut dysmotility that was not suspected based on the patient's presentation. Therefore patients with suspected GI dysmotility should undergo tests of the entire GI tract, as reported symptoms are poor indicators of the affected gut region.

1243 The Association Between Gastroparesis and Slow Transit Constipation as Seen by Wireless Motility Capsule (WMC)

INTRODUCTION: Gastroparesis refers to delayed gastric emptying in the absence of a gastric outlet obstruction, as diagnosed by &gt;10% gastric retention at 4 hours on Gastric Emptying Scintigraphy (GES). It presents with nausea/vomiting, upper abdominal fullness/discomfort, and early satiety. Several conditions can predispose patients to developing the disease, but ∼50% of affected patients are found to have idiopathic gastroparesis. The gastrointestinal tract is well connected through a series of neuronal reflexes that act to stimulate/inhibit specific segments based on stimuli detected at other “upstream or downstream” locations. The existence of a “cologastric brake” has been postulated in the past – where stimuli in the colon activate ascending tracts that may modulate upper gastrointestinal function. Based on this premise, the aim of our study was to determine the relationship between constipation and gastroparesis. METHODS: We conducted a retrospective study of patients who had undergone both GES as well as Wireless Motility Capsule (WMC) testing at our institution. Patients were divided into two groups based on the results of the GES: normal gastric emptying or gastroparesis. Constipation was assessed via WMC and anorectal manometry (when available). Demographic data, co-morbidities, selected labs, and medications were analyzed. RESULTS: A total of 224 patients were reviewed (101 with normal gastric emptying and 123 with gastroparesis). Mean colonic transit time was 2,321 min (normal &lt;3,540 min) for patients with normal gastric emptying and 2,665 min for patients with gastroparesis (P = 0.361). There were no significant differences between the groups in demographics, co-morbidities, labs, or medications with the exception of prokinetics (P = 0.004) which were more common in the gastroparesis group. Univariate logistical regression found no association between slow-transit constipation and mild/moderate gastroparesis (OR 1.13/0.92, P = 0.82/0.81) but did find a correlation with severe gastroparesis (OR 2.45, P = 0.01). This relationship was strengthened with the exclusion of diabetes mellitus (OR 3.5, P = 0.008). Dyssynergic defecation did not appear to be associated with gastroparesis regardless of severity. CONCLUSION: Severe gastroparesis appears to be associated with an increased prevalence of slow-transit constipation – even more so after eliminating confounders (diabetes mellitus). Conversely, dyssynergic defecation does not appear to have any impact on gastric emptying.

Differential Longitudinal Symptom and Quality of Life (QOL) Outcomes on Selected Medications in Patients With Suspected Gastroparesis With Delayed versus Normal Colon Transit on Wireless Motility Capsule Testing

Introduction: Patients with suspected gastroparesis may also report intestinal symptoms such as constipation and/or show delayed colon transit on wireless motility capsules (WMC) testing. However, the impact of colonic dysfunction on gastroparesis and whether its treatment improves upper and lower GI symptoms and quality of life (QOL) in patients with delayed vs. normal colon transit is unknown. This prospective multicenter study determined if treatment decisions based on the results of WMC testing are associated with improvements in upper and lower GI symptoms and QOL in patients with suspected gastroparesis. Methods: 150 subjects with suspected gastroparesis underwent concurrent WMC and gastric emptying scintigraphy. Based on test results, investigators recommended treatment(s) (prokinetic, neuromodulator, constipation therapies). The clinical outcomes for various treatment modalities as assessed by symptoms (PAGI-SYM/GCSI) and QOL (PAGI-QOL) at 6 months were compared between the normal (NCT) and delayed colon transit (DCT)(>59 hours by WMC) groups. Results: 53 (35%) had delayed gastric transit; 45 (30%) subjects had DCT; 100 (67%) had NCT; 5 (3%) did not have colonic transit data. 50 subjects received prokinetics; 71 received neuromodulators; 54 received constipation therapies (linaclotide 22, lubiprostone 9, PEG 19, others 4). Overall PAGI-SYM scores improved on prokinetics and neuromodulators with both NCT and DCT, but improved on constipation therapies only with DCT (Table).PAGI-QOL scores improved on all 3 drug classes with DCT, but improved only on prokinetics with NCT. When comparing individual symptoms, constipation therapies were associated with reduced GCSI, fullness, and constipation scores and trends towards less bloating with DCT, but did not affect N/V, pain, or diarrhea (Figures A-B). Diarrhea (P=0.049) and upper abdominal pain (P=0.048) scores were higher on constipation therapies in DCT group. Conversely, constipation therapies were associated with trends to less fullness with NCT and no benefits for other symptoms. Conclusion: Delayed colon transit was found in 30% of patients with suspected gastroparesis and treatment with neuromodulators and constipation therapies was associated with selective overall improvements in gastroparetic and bowel symptoms and QOL in this group. By identifying colonic dysfunction, wireless motility capsule tests could provide improved overall treatment benefit(s) in patients with suspected gastroparesis.158_A Figure 1. Longitudinal Outcomes on Different Medication Classes in Normal vs. Delayed Colon Transit by Wireless Motility Capsule158_B Figure 2. Normal Colon Transit158_C Figure 3. Delayed Colon Transit

Correlation Between GAD Antibody Levels and Severity of Gastrointestinal Motility Dysfunction as Determined by Wireless Motility Capsule Testing

Introduction: There is an increasing body of evidence identifying an immune mediated role in the pathogenesis of both paraneoplastic and non-paraneoplastic gastrointestinal dysmotility. One such mechanism is an antibody mediated pathway involving Glutamic Acid Decarboxylase (GAD). Our objective in this study is to determine if the level of circulating GAD antibody correlates with the severity of gastrointestinal dysmotility, or the number of bowel segments impacted as determined by wireless motility capsule(WMC) testing. Methods: The study was conducted as a retrospective cohort analysis. We included all patients seen at The Cleveland Clinic who had a WMC study ordered between 2009 to 2017, and who also had positive Glutamic Acid Decarboxyase (GAD) antibodies. Patients were identified by CPT codes for WMC in the electronic medical record. Patients were excluded from the study if they failed the WMC due to technical failure. A total 304 completed WMT and also had GAD antibody measured. Of these patients, 35 had positive GAD antibodies (>5 IU/mL). Gastric emptying time (GET), Small Bowel Transit time (SBTT), and Large Bowel Transit time (LBTT) were measured using WMC data. The data from the WMC was compared to corresponding GAD antibody levels using pairwise correlation analysis after eliminating outliers. Additionally, the results were transformed to categorical data (abnormal or not) for evaluation of portions of the gastrointestinal tract involved. Abnormal measurements included a GET >4h, SBTT > 6h, or an LBTT >59h. Results: Results were calculated based on GET, SBTT and LBTT independently, as well as SLBTT and WGTT relative to the GAD antibodies. GAD antibody concentrations do not appear to correlate with the degree of gastrointestinal dysmotility as measured by WMC (Table 1). Conclusion: Based on this review of data, it seems that GAD antibody levels cannot be used as a predictor of disease severity, or to predict the location of gastrointestinal dysmotility. However, more research is needed. Empiric treatment with IVIg should not be used in patients with high GAD antibody levels in the absence of additional supportive data. A larger sample size is needed to confirm the findings of this study, and to identify further correlations.441 Figure 1. Correlation of emptying times and GAD levels

Comparing Longitudinal Overall and Individual Symptom Outcomes on Neuromodulator versus Prokinetic Drugs in Patients With Symptoms Suspicious for Gastroparesis but With Non—Delayed Gastric Emptying

Introduction: Most patients with suspected gastroparesis do not have delayed gastric emptying. These patients are often treated with prokinetic agents but neuromodulator drugs are also given to reduce symptoms. Relative benefits of each drug class are unknown. In a multicenter study, we hypothesized that patients with suspected gastroparesis with non—delayed gastric emptying on scintigraphy (GES) or wireless motility capsules (WMC) show differential symptom benefits after prescribing neuromodulator vs. prokinetic medications. Methods: Management plans were devised for 150 patients with suspected gastroparesis. Investigators reviewed concurrent GES and WMC results and recommended therapy changes for those patients with non—delayed gastric emptying by GES (<10% 4 hr retention) or WMC (emptying <5 hr). Symptom (GCSI/PAGI—SYM) scores at baseline and 6 months were related to neuromodulator and prokinetic recommendations.1201_A Figure 1. Overall GCSI Reductions on Neuromodulators and Prokinetics in Patients with Non—Delayed Gastric Emptying1201_B Figure 2. Improvements in Individual Symptoms on Neuromodulators and Prokinetics in Patients with Non—Delayed Gastric EmptyingResults: 76% and 65% of patients had non—delayed gastric emptying by GES and WMC. 64 were prescribed neuromodulators including antidepressants—42 (mirtazapine/tricyclics—35), gabapentin—10, buspirone—9, and other—5. 49 received prokinetics including dopamine receptor antagonists (DRAs) (metoclopramide/domperidone—34) and pure prokinetics (macrolides, pyridostigmine, botulinum toxin—22). At 6 months, neuromodulators and prokinetics reduced overall GCSI scores similarly (Table). DRAs but not pure prokinetics reduced overall scores. Of neuromodulators, antidepressants and buspirone but not gabapentin reduced overall GCSIs. Individual symptoms improved with both drug classes; N/V improved less than other symptoms on neuromodulators but not prokinetics (Figure). DRAs but not pure prokinetics reduced all individual symptoms (P<0.05). Antidepressants but not gabapentin reduced all individual symptoms with GES vs. fullness and pain with WMC (P<0.05). Buspirone lowered fullness and bloating (P<0.05). Conclusion: Neuromodulator and prokinetic drugs are associated with differential benefits in patients with suspected gastroparesis with non—delayed gastric emptying on GES and WMC testing. Both drug classes are associated with improved symptoms, but lower N/V responses on neuromodulators suggest they are less effective antiemetics than prokinetics. Dopamine antagonists are associated with better responses than pure prokinetics. Antidepressants and buspirone relate to better responses than gabapentin. Our results offer unique insight into treating this large, distinct patient group.

Regional gastrointestinal pH profile is altered in patients with type 1 diabetes and peripheral neuropathy.

Gastrointestinal (GI) symptoms, such as nausea and bloating, are common in people with type 1 diabetes (T1DM). Autonomic dysfunction can lead to changes in the GI secreto-motor function which can be associated with GI symptom development. We hypothesized that regional pH profiles in T1DM differs from health and would be associated with objective physiological/clinical markers. Forty-seven T1DM with confirmed diabetic sensory peripheral neuropathy and 41 healthy age-matched subjects underwent standardized wireless motility capsule testing. T1DM completed the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale. Disease duration, glycemic control, insulin usage, and 24-hour heart rate variability testing were evaluated. In comparison to healthy subjects, gastric, and large bowel median pH were lower in T1DM (1.8±1.6 vs 2.9±1.5, P=0.001 and 6.7±0.6 vs 7.0±0.5, P=0.003, respectively). Additionally, change in pH across the pylorus was lower while change in pH across the ileocecal junction was higher in T1DM (5.2±1.5 vs 5.8±0.5, P=0.003 and 1.8±0.4 vs 1.3±0.4, P<0.0001, respectively). No difference was found in small bowel median pH. Gastric median pH was associated with small bowel transit time (r=0.30, P=0.049). Change in pH across the pylorus was negatively associated with fasting glycose (r=-0.35, P=0.027). Small bowel median pH was associated with nausea (r=0.42, P=0.005) and small bowel transit time (r=0.48, P=0.0007). Large bowel median pH was associated with nausea (r=0.35, P=0.018) and the total GCSI score (r=0.34, P=0.023). The GI pH profile in T1DM with DSPN is different from healthy subjects. Changes in pH profile may have important therapeutic implications and influence pharmacotherapeutic bioavailability.

Chronic constipation.

Chronic constipation is a prevalent condition that severely impacts the quality of life of those affected. Several types of primary chronic constipation, which show substantial overlap, have been described, including normal-transit constipation, rectal evacuation disorders and slow-transit constipation. Diagnosis of primary chronic constipation involves a multistep process initiated by the exclusion of 'alarm' features (for example, unintentional weight loss or rectal bleeding) that might indicate organic diseases (such as polyps or tumours) and a therapeutic trial with first-line treatments such as dietary changes, lifestyle modifications and over-the-counter laxatives. If symptoms do not improve, investigations to diagnose rectal evacuation disorders and slow-transit constipation are performed, such as digital rectal examination, anorectal structure and function testing (including the balloon expulsion test, anorectal manometry or defecography) or colonic transit tests (such as the radiopaque marker test, wireless motility capsule test, scintigraphy or colonic manometry). The mainstays of treatment are diet and lifestyle interventions, pharmacological therapy and, rarely, surgery. This Primer provides an introduction to the epidemiology, pathophysiological mechanisms, diagnosis, management and quality of life associated with the commonly encountered clinical problem of chronic constipation in adults unrelated to opioid abuse.