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Gastroparesis is a prevalent condition that produces symptoms of delayed gastric emptying in the absence of physical blockage. Over the past 5 years, considerable advances have been made in understanding gastroparesis, and the number of treatment options has expanded. William Hasler thus provides a timely Review of the pathogenesis, diagnosis and management of this condition. Gastroparesis is a prevalent condition that produces symptoms of delayed gastric emptying in the absence of physical blockage. The most common etiologies of gastroparesis are idiopathic, diabetic, and postsurgical disease, although some cases stem from autoimmune, paraneoplastic, neurologic or other conditions. Histologic examination of gastric tissues from patients with severe gastroparesis reveals heterogeneous and inconsistent defects in the morphology of enteric neurons, smooth muscle and interstitial cells of Cajal, and increased levels of inflammatory cells. Diagnosis is most commonly made by gastric emptying scintigraphy; however, wireless motility capsules and nonradioactive isotope breath tests have also been validated. A range of treatments have been used for gastroparesis including dietary modifications and nutritional supplements, gastric motor stimulatory or antiemetic medications, endoscopic or surgical procedures, and psychological interventions. Most treatments have not been subjected to controlled testing in patients with gastroparesis. The natural history of this condition is poorly understood. Active ongoing research is providing important insights into the pathogenesis, diagnosis, treatment and outcomes of this disease. Key Points Gastroparesis causes chronic symptoms of delayed gastric emptying; it can promote extraintestinal complications, and it leads to significant morbidity and health-care utilization Diabetic, idiopathic and postsurgical gastroparesis are the most common etiologies of disease Histopathology reveals defects in the morphology of enteric neurons, smooth muscle and interstitial cells of Cajal; in addition, the loss of neurotransmitters and increased levels of inflammatory cells suggests a heterogeneous pathogenesis of disease Techniques to measure gastric emptying, including gastric emptying scintigraphy, wireless motility capsule monitoring and breath tests, are being validated for the diagnosis of gastroparesis but controversies persist Treatments for gastroparesis include prokinetic and antiemetic drugs, endoscopic and surgical techniques, and nutritional and psychologic interventions; however, controlled testing is still needed to confirm their benefits Ongoing research is defining the natural history of gastroparesis

Fluids sampled from the gastrointestinal (GI) tract are of interest for evaluating the bioequivalence of oral medications, and more generally for evaluating GI-related diseases, and for profiling the individual gut microbiome. Existing options for capturing multiple fluid samples from specific locations in the GI tract are limited and invasive, particularly for the small intestine. Here, we report the development of an ingestible capsule for the collection of multiple fluid samples along the GI tract; we additionally report the use of data from sensors within the capsule to determine the sampling regions. The capsule has an ingestible size of Φ14 × 42 mm 3 . Within this volume, it includes three separate cartridges that capture and retain samples within capillaries; a stepper motor for positioning the sampling cartridges at a sampling port; a 3-axis accelerometer that enables a new method of correlating sample location; a microcontroller with wireless communication and sensor data storage capabilities; and batteries to power the device. We describe in vitro characterization and in vivo tests performed with canine models that have successfully verified the capabilities of the capsule. Fluid samples from the stomach, small intestine, and colon regions of the GI tract are identified by inertial measurements taken within the capsule, and correlated to measurements of the concentration of mesalamine (a drug used for testing) and the bile salt profile in each region, respectively.

This consensus statement from the members of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine recommends a standardized method for measuring gastric emptying (GE) by scintigraphy. A low-fat, egg-white meal with imaging at 0, 1, 2, and 4 h after meal ingestion, as described by a published multicenter protocol, provides standardized information about normal and delayed GE. Adoption of this standardized protocol will resolve the lack of uniformity of testing, add reliability and credibility to the results, and improve the clinical utility of the GE test.

The gastrointestinal environment in which drug products need to disintegrate before the drug can dissolve and be absorbed has not been studied in detail due to limitations, especially invasiveness of existing techniques. Minimal in vivo data is available on undisturbed gastrointestinal motility to improve relevance of predictive dissolution models and in silico tools such as physiologically-based pharmacokinetic models. Recent advances in magnetic resonance imaging methods could provide novel data and insights that can be used as a reference to validate and, if necessary, optimize these models. The conventional method for measuring gastrointestinal motility is via a manometric technique involving intubation. Nevertheless, it is feasible to measure gastrointestinal motility with magnetic resonance imaging. The aim of this study was is to develop and validate a magnetic resonance imaging method using the most recent semi-automated analysis method against concomitant perfused manometry method. Eighteen healthy fasted participants were recruited for this study. The participants were intubated with a water-perfused manometry catheter. Subsequently, stomach motility was assessed by cine-MRI acquired at intervals, of 3.5min sets, at coronal oblique planes through the abdomen and by simultaneous water perfused manometry, before and after administration of a standard bioavailability / bioequivalence 8 ounces (~240mL) drink of water. The magnetic resonance imaging motility images were analysed using Spatio-Temporal Motility analysis STMM techniques. The area under the curve of the gastric motility contractions was calculated for each set and compared between techniques. The study visit was then repeated one week later. Data from 15 participants was analysed. There was a good correlation between the MRI antral motility plots area under the curve and corresponding perfused manometry motility area under the curve (r = 0.860) during both antral contractions and quiescence. Non-invasive dynamic magnetic resonance imaging of gastric antral motility coupled with recently developed, semi-automated magnetic resonance imaging data processing techniques correlated well with simultaneous, 'gold standard' water perfused manometry. This will be particularly helpful for research purposes related to oral absorption where the absorption of a drug is highly depending on the underlying gastrointestinal processes such as gastric emptying, gastrointestinal motility and availability of residual fluid volumes. This trial was registered at ClinicalTrials.gov as NCT03191045.

Generalized gut transit abnormalities are observed in some diabetics with gastroparesis. Relations of gastric emptying abnormalities to colon contractile dysfunction are poorly characterized. We measured colon transit and contractility using wireless motility capsules (WMC) in 41 healthy subjects, 12 diabetics with gastroparesis (defined by gastric retention >5 hours), and 8 diabetics with normal gastric emptying (≤5 hours). Overall numbers of colon contractions >25 mmHg were calculated in all subjects and were correlated with gastric emptying times for diabetics with gastroparesis. Colon transit periods were divided into quartiles by time and contraction numbers were calculated for each quartile to estimate regional colon contractility. Colon transit in diabetics with gastroparesis was prolonged vs. healthy subjects (P<0.0001). Overall numbers of colon contractions in gastroparetics were lower than controls (P = 0.02). Diabetics with normal emptying showed transit and contraction numbers similar to controls. Gastric emptying inversely correlated with overall contraction numbers in gastroparetics (r = -0.49). Numbers of contractions increased from the 1st to 4th colon transit quartile in controls and diabetics with normal emptying (P≤0.04), but not gastroparetics. Numbers of contractions in the 3rd and 4th quartiles were reduced in gastroparetics vs. healthy controls (P≤0.05) and in the 4th quartile vs. diabetics with normal emptying (P = 0.02). Numbers of contractions were greatest in the final 15 minutes of transit, but were reduced in gastroparetics vs. healthy controls and diabetics with normal emptying (P≤0.005). On multivariate analyses, differences in numbers of contractions were not explained by demographic or clinical variables. In conclusion, diabetics with gastroparesis exhibit delayed colon transit associated with reductions in contractions that are prominently blunted in latter transit phases and which correlate with delayed gastric emptying, while diabetics with normal emptying show no significant colonic impairments. These findings emphasize diabetic gastroparesis may be part of a generalized dysmotility syndrome.

Background Gastric food residue frequently is observed on endoscopy despite fasting. Aims To delineate factors promoting endoscopic food retention in the stomach. Methods Two series of analyses were performed. Magnitudes of retained food in 834 patients from an endoscopy database were related to obstructive versus non-obstructive etiologies and gastric emptying findings. Emptying delays in 619 patients from a scintigraphy database were associated with endoscopic food retention, gastroparesis etiologies, and medications that modify gastric transit. Results On endoscopy, 310 (37 %) had large, 338 (41 %) showed medium, and 103 (12 %) exhibited small amounts of retained food in the stomach. Of 433 patients with definable etiologies of food retention, 106 (24 %) had obstructive causes. One hundred three of 327 (31 %) with non-obstructive conditions underwent scintigraphy showing mean 52 ± 29 % 4-h retention. From the scintigraphy database, 164/619 patients (26 %) with delayed emptying exhibited food retention on endoscopy. Four-hour scintigraphic retention was greater with versus without retained food (41 ± 25 vs. 32 ± 22 %, P  < 0.001). Retained food occurred more frequently with postsurgical (28/69, 41 %) versus diabetic (33/139, 24 %) and idiopathic (65/294, 22 %) gastroparesis ( P  = 0.006). Opiate use was more prevalent with increasing food retention ( P  = 0.02), while other medications that delay or accelerate emptying did not relate to retained food. Conclusions Gastric food retention has obstructive and non-obstructive causes, and is found in one-quarter of gastroparesis, especially postsurgical cases. Gastric emptying delays correlate with amounts of retained food on endoscopy. Retention is influenced by opiates, but not other medications. These analyses delineate pathogenic factors promoting gastric food retention.

Testing to define delayed gastric emptying is required to diagnose gastroparesis; rapid emptying is found in other patients. Commonly performed methods of gastric emptying testing include scintigraphy and breath testing. The SmartPill wireless motility capsule (WMC) system is US 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. WMC 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. Acceptance of trial data confirming usefulness of WMC testing in suspected gastric motor disorders has been hampered by small sample sizes and design limitations. Ongoing multicenter studies will validate the utility of WMC methods in patients with suspected gastroparesis and other upper gastrointestinal motor disorders.

Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in poorly controlled diabetes with gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24 week open-label pilot prospective study of CSII plus CGM. The primary safety outcome was combined numbers of mild, moderate, and severe hypoglycemic events at screening and 24 weeks treatment. Secondary outcomes included glycemic excursions on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal tolerance. Combined mild, moderate, and severe hypoglycemic events occurred similarly during the screening/run-in (1.9/week) versus treatment (2.2/week) phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and hemoglobin A1c decreased from 9.4±1.4% to 8.3±1.3% (P = 0.001) on CSII plus CGM. Symptom scores decreased from 29.3±7.1 to 21.9±10.2 with lower nausea/vomiting, fullness/early satiety, and bloating/distention scores (P≤0.001). Quality-of-life scores improved from 2.4±1.1 to 3.1±1.1 (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420±258 to 487±312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared to be safe with minimal risks of hypoglycemic events and associated improvements in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance in patients with poorly controlled diabetes and gastroparesis. This study supports the safety, feasibility, and potential benefits of improving glycemic control in diabetic gastroparesis.