Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis.

BACKGROUND & AIMS: Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear. METHODS: One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables. RESULTS: In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.).

Clinical Presentation of Small Intestinal Bacterial Overgrowth from Aerodigestive Tract Bacteria Versus Colonic-Type Bacteria: A Comparison Study.

BACKGROUND: Small Intestinal Bacterial Overgrowth (SIBO) is a heterogenous syndrome from excessive bacteria in the small intestine lumen. It is unknown if differences in type of bacterial overgrowth lead to differences in symptoms. METHODS: Patients with suspected SIBO were recruited prospectively. Exclusion criteria were probiotics, antibiotics, or bowel prep in preceding 30 days. Clinical characteristics, risk factors, and labs were collected. Proximal jejunal aspiration via upper enteroscopy was performed. Aerodigestive tract (ADT) SIBO was defined as > 105 CFU/mL of oropharyngeal and respiratory bacteria. Colonic-type SIBO was defined as > 104 CFU/mL of distal small bowel and colon bacteria. Aims were to compare symptom profiles, clinical complications, labs, and underlying risk factors between ADT and colonic-type SIBO. KEY RESULTS: We consented 166 subjects. Aspiration was not obtained in 22 and SIBO was found in 69 (49%) of 144 subjects. Daily abdominal distention trended towards more prevalent in ADT SIBO versus colonic-type SIBO (65.2% vs 39.1%, p = 0.09). Patient symptom scores were similar. Iron deficiency was more prevalent in ADT SIBO (33.3% vs 10.3%, p = 0.04). Subjects with colonic-type SIBO were more likely to have a risk factor for colonic bacteria colonization (60.9% vs 17.4%, p = 0.0006). Subjects with ADT SIBO were more likely to have a risk factor for diminished gastric acid (91.3% vs 67.4%, p = 0.02). CONCLUSIONS & INFERENCES: We found differences in iron deficiency and underlying risk factors between ADT and colonic-type SIBO. However, distinct clinical profiles remained elusive. Future research is needed to develop validated symptom assessment tools and distinguish cause from correlation.

Pyloric Functional Lumen Imaging Probe Measurements Are Dependent on Balloon Position.

Background/Aims: The functional lumen imaging probe (FLIP) device has been used to assess pyloric dysfunction in patients with gastroparesis. We aim to investigate whether varying FLIP catheter positions affect pyloric FLIP measurements. Methods: Patients undergoing endoscopy for chronic unexplained nausea and vomiting (CUNV) or gastroparesis were prospectively enrolled. FLIP balloon was adjusted for 3 positions within the pylorus: (1) proximal position, 75% of FLIP balloon in the duodenum and 25% in the antrum; (2) middle position, 50% in the duodenum and 50% in the antrum; and (3) distal position, 25% in the duodenum and 75% in the antrum. Pylorus cross-sectional area (CSA), intra-bag pressure (P), and distensibility indices (DI) were measured for 30, 40, and 50-mL balloon volumes. Fluoroscopic images were obtained to confirm FLIP balloon geometry. Data was analyzed separately using FLIP Analytic and customized MATLAB software. Results: Twenty-two patients with CUNV (n = 4) and gastroparesis (n = 18) were enrolled. Pressures were significantly higher in the proximal position compared to the middle and distal positions. CSA measurements were significantly higher at the proximal and middle positions for 30-mL and 40-mL volume compared to the distal position values. DI values were significantly lower at the proximal positions for 40-mL and 50-mL distensions when compared to the middle and distal positions. Fluoroscopic images confirmed increased balloon bending when placed mostly in the duodenum. Conclusions: FLIP balloon position within the pylorus directly affects balloon geometry which significantly affects P, CSA, and DI measurements. Standardized pyloric FLIP protocols and balloon design adjustments are needed for the continued application of this technology to the pylorus.

Safety of same-day discharge after peroral endoscopic myotomy.

There are limited data on the safety of same-day discharge (SDD) after peroral endoscopic myotomy (POEM). The aim of our study is to assess the frequency and relationship to POEM for emergency department (ED) visits and hospitalizations after SDD in these patients. We retrospectively identified consecutive patients between November 2019 and August 2021 who underwent POEM with SDD and at least 6 months follow-up. Criteria for SDD includes: (1) no serious procedure-related adverse event; (2) post-POEM esophagram without leak; (3) stable vital signs; (4) ability to take liquids orally; (5) pain controlled without IV analgesia; (6) adequate social support; (7) American Society of Anesthesiologists (ASA) class I-III. A causative relationship between POEM and ED visits and hospitalizations was assigned by consensus. Out of 185 POEMs performed, 78 (41.7%, 42M, mean 51±16 years) had SDD. Within 30 days of POEM, 8 ED visits occurred in 7/78 (9%) patients and 2 (25%) were considered related to POEM; hospitalization was required in 3 (38%). After 30 days, 11 ED visits occurred in 10/78 (12.8%) patients and 1 (9%) was considered related to POEM; hospitalization was required in 5 (45%). In this study of consecutive SDD patients after POEM, 3/19 (16%) ED visits and 2/8 (25%) hospitalizations within 6 months were considered related to the procedure. Therefore, eligible patients who follow and fulfill a strict protocol after POEM may be safely discharged the same day.

Symptom Association for Gastroesophageal Reflux Disease by pH Monitoring After Peroral Endoscopic Myotomy.

INTRODUCTION: There are limited data correlating symptoms with reflux episodes during pH studies after peroral endoscopic myotomy. METHODS: Consecutive patients who underwent POEM followed up ≥6 months later by 48-hour ambulatory wireless pH testing off antisecretory therapy were identified. Reflux symptom association was defined as symptom association probability >95%. RESULTS: The most frequent symptoms of heartburn (47.2%), cough (45.1%), and chest pain (39.6%) were associated with a positive reflux symptom association (symptom association probability >95%) in 20.9%, 17.1%, and 19.4%, respectively. DISCUSSION: There is poor correlation between reported symptoms and esophageal acid exposure during pH testing after POEM.

Comparison of functional lumen imaging probe and high-resolution manometry to assess response after peroral endoscopic myotomy.

BACKGROUND AND AIMS: Outcomes after peroral endoscopic myotomy (POEM) are assessed clinically by the Eckardt score (ES) or objectively by high-resolution manometry (HRM) and functional lumen imaging probe (FLIP). This study compared HRM and FLIP to evaluate clinical response after POEM. METHODS: This was a single tertiary center retrospective study of consecutive patients who underwent POEM for treatment-naive achalasia and with ≥6 months of follow-up. Baseline and follow-up testing in all patients included ES, HRM, and FLIP of the esophagogastric junction (EGJ). A normal post-POEM (or normalized) EGJ distensibility index (EGJ-DI) >2.8 mm2/mm Hg, maximum EGJ diameter (MxEGJD) ≥14 mm, and integrated relaxation pressure (IRP) <15 mm Hg were compared with a clinical response, defined as ES ≤3. RESULTS: Eighty-seven patients (58% men, mean age 51 ± 17 years) were included. Overall clinical response by ES, IRP, MxEGJD, and EGJ-DI were 97.7%, 86.2%, 75.9%, and 92.0%, respectively. The sensitivity of a normal IRP (87.1% [95% confidence interval {CI}, 78.0-93.4]) was similar to the sensitivity of a normal MxEGJD (75.3% [95% CI, 64.7-84.0], P = .053) and normal EGJ-DI (91.8% [95% CI, 83.8%-96.6%], P = .39) after POEM to predict clinical response. However, the sensitivity of a normal post-POEM EGJ-DI was superior to a normal post-POEM MxEGJD (P = .001) to predict clinical response. There was no difference in the area under the curve of a normal MxEGJD or EGJ-DI to predict a normal IRP (P = .956) after POEM. CONCLUSIONS: Normal FLIP metrics ≥6 months after POEM for achalasia show good to excellent sensitivity but are equivalent to a normalized IRP by HRM to predict clinical response by ESs. FLIP may be used as an alternative to HRM to assess lower esophageal sphincter response to POEM in these patients. (Clinical trial registration number: NCT02770859.).

Automatic assessment of human gastric motility and emptying from dynamic 3D magnetic resonance imaging.

BACKGROUND: Time-sequenced magnetic resonance imaging (MRI) of the stomach is an emerging technique for non-invasive assessment of gastric emptying and motility. However, an automated and systematic image processing pipeline for analyzing dynamic 3D (ie, 4D) gastric MRI data has not been established. This study uses an MRI protocol for imaging the stomach with high spatiotemporal resolution and provides a pipeline for assessing gastric emptying and motility. METHODS: Diet contrast-enhanced MRI images were acquired from seventeen healthy humans after they consumed a naturalistic contrast meal. An automated image processing pipeline was developed to correct for respiratory motion, to segment and compartmentalize the lumen-enhanced stomach, to quantify total gastric and compartmental emptying, and to compute and visualize gastric motility on the luminal surface of the stomach. KEY RESULTS: The gastric segmentation reached an accuracy of 91.10 ± 0.43% with the Type-I error and Type-II error being 0.11 ± 0.01% and 0.22 ± 0.01%, respectively. Gastric volume decreased 34.64 ± 2.8% over 1 h where the emptying followed a linear-exponential pattern. The gastric motility showed peristaltic patterns with a median = 4 wave fronts (range 3-6) and a mean frequency of 3.09 ± 0.07 cycles per minute. Further, the contractile amplitude was stronger in the antrum than in the corpus (antrum vs. corpus: 5.18 ± 0.24 vs. 3.30 ± 0.16 mm; p < 0.001). CONCLUSIONS & INFERENCES: Our analysis pipeline can process dynamic 3D MRI images and produce personalized profiles of gastric motility and emptying. It will facilitate the application of MRI for monitoring gastric dynamics in research and clinical settings.

Baseline Predictors of Longitudinal Changes in Symptom Severity and Quality of Life in Patients With Suspected Gastroparesis.

BACKGROUND & AIMS: Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis. METHODS: One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL. RESULTS: Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stools by Bristol stool form score, and presence of functional dyspepsia (FD) by Rome III criteria, were predictive of more severe upper GI symptoms. Even after controlling for these clinical factors, delayed gastric emptying by GES or WMC was associated with worse symptom severity and QOL scores. Low gastric and elevated small bowel contractile parameters by WMC were also independently associated with more severe upper GI symptoms and worse QOL scores. CONCLUSIONS: Baseline features, including demographic and clinical variables, delayed gastric emptying and abnormal gastrointestinal contractility, were independent predictors of more severe longitudinal symptoms and worse quality of life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no: NCT02022826.

Human organ donor-derived vagus nerve biopsies allow for well-preserved ultrastructure and high-resolution mapping of myelinated and unmyelinated fibers.

The vagus nerve provides motor, sensory, and autonomic innervation of multiple organs, and electrical vagus nerve stimulation (VNS) provides an adjunctive treatment option for e.g. medication-refractory epilepsy and treatment-resistant depression. The mechanisms of action for VNS are not known, and high-resolution anatomical mapping of the human vagus nerve is needed to better understand its functional organization. Electron microscopy (EM) is required for the detection of both myelinated and unmyelinated axons, but access to well-preserved human vagus nerves for ultrastructural studies is sparse. Intact human vagus nerve samples were procured intra-operatively from deceased organ donors, and tissues were immediately immersion fixed and processed for EM. Ultrastructural studies of cervical and sub-diaphragmatic vagus nerve segments showed excellent preservation of the lamellated wall of myelin sheaths, and the axolemma of myelinated and unmyelinated fibers were intact. Microtubules, neurofilaments, and mitochondria were readily identified in the axoplasm, and the ultrastructural integrity of Schwann cell nuclei, Remak bundles, and basal lamina was also well preserved. Digital segmentation of myelinated and unmyelinated axons allowed for determination of fiber size and myelination. We propose a novel source of human vagus nerve tissues for detailed ultrastructural studies and mapping to support efforts to refine neuromodulation strategies, including VNS.

Evaluation of timed barium esophagram after per-oral endoscopic myotomy to predict clinical response.

Background and study aims The aim of this study was to evaluate whether timed barium esophagram within 24 hours post-per-oral endoscopic myotomy (POEM) (TBE-PP) could predict clinical outcomes. Patients and methods This was a single-center retrospective study of prospectively collected data on consecutive patients with ≥ 6-month follow-up who underwent POEM followed by TBE-PP. Esophageal contrast retention 2 minutes after TBE-PP was assessed as Grade 1 (< 10 %), 2 (10 %-49 %), 3 (50 %-89 %) or 4 (> 90 %). Eckardt score, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM) and function lumen imaging probe (FLIP) of the esophagogastric junction (EGJ) were obtained at baseline. These tests along with pH testing of antisecretory therapy were repeated 6 and 24 months after POEM. Clinical response by Eckardt score ≤ 3, EGJ-distensibility index (EGJ-DI) > 2.8 mm 2 /mm Hg, and integrated relaxation pressure (IRP) < 15 mm Hg and incidence of gastroesophageal reflux disease (GERD) were compared by transit time. Results Of 181 patients (58 % male, mean 53 ±â€Š17 yr), TBE-PP was classified as Grade 1 in 122 (67.4 %), Grade 2 in 41 (22.7 %), Grade 3 in 14 (7.7 %) and Grade 4 in 4 (2.2 %). At 6 months, overall clinical response by ES (91.7 %), IRP (86.6 %), EGJ-DI (95.7 %) and the diagnosis of GERD (68.6 %) was similar between Grade 1 and Grade 2-4 TBE-PP. At 24 months, Grade 1 had a higher frequency of a normal IRP compared to Grades 2-4 (95.7 % vs. 60 %, P  = 0.021) but overall response by ES (91.2 %), EGJ-DI (92.3 %) and the diagnosis of GERD (74.3 %) were similar. Conclusions Contrast emptying rate by esophagram after POEM has limited utility to predict clinical response or risk of post-procedure GERD.