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Gastroenterology Jan 2022Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review... (Review)
Review
Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review addresses the normal emptying of solids and liquids from the stomach and details the myogenic and neuromuscular control mechanisms, including the specialized function of the pyloric sphincter, that result in normal emptying, based predominantly on animal research. A clear understanding of fundamental mechanisms is necessary to comprehend derangements leading to gastroparesis, and additional research on human gastric muscles is needed. The section on pathophysiology of gastroparesis considers neuromuscular diseases that affect nonsphincteric gastric muscle, disorders of the extrinsic neural control, and pyloric dysfunction that lead to gastroparesis. The potential cellular basis for gastroparesis is attributed to the effects of oxidative stress and inflammation, with increased pro-inflammatory and decreased resident macrophages, as observed in full-thickness biopsies from patients with gastroparesis. Predominant diagnostic tests involving measurements of gastric emptying, the use of a functional luminal imaging probe, and high-resolution antral duodenal manometry in characterizing the abnormal motor functions at the gastroduodenal junction are discussed. Management is based on supporting nutrition; dietary interventions, including the physical reduction in particle size of solid foods; pharmacological agents, including prokinetics and anti-emetics; and interventions such as gastric electrical stimulation and pyloromyotomy. These are discussed briefly, and comment is added on the potential for individualized treatments in the future, based on optimal gastric emptying measurement and objective documentation of the underlying pathophysiology causing the gastroparesis.
Topics: Animals; Enteric Nervous System; Gastric Emptying; Gastroparesis; Humans; Predictive Value of Tests; Pylorus; Treatment Outcome
PubMed: 34717924
DOI: 10.1053/j.gastro.2021.10.028 -
American Journal of Physiology.... Aug 2021Until recently, gastric motility measurements in humans were mostly limited to accommodation (using barostat or 3-dimensional imaging studies of gastric volume) and... (Review)
Review
Until recently, gastric motility measurements in humans were mostly limited to accommodation (using barostat or 3-dimensional imaging studies of gastric volume) and gastric emptying tests, the latter being the only one performed in routine clinical care. Accurate and easy to use techniques were lacking to assess pyloric function in health and disease. Recently, pyloric distensibility has been developed and validated to assess pyloric opening. Several studies confirmed that pyloric distensibility was decreased in gastroparesis and correlated with gastric emptying as well as gastroparesis symptoms. In addition, pyloric distensibility may predict outcome of endoscopic techniques targeting the pylorus, namely intrapyloric botulinum toxin injection and gastric per-oral pyloromyotomy. Pyloric distensibility appears therefore to be a promising and useful new tool in the workup of gastroparesis patients.
Topics: Animals; Gastric Emptying; Gastroparesis; Humans; Pyloromyotomy; Pylorus
PubMed: 34160292
DOI: 10.1152/ajpgi.00460.2020 -
American Journal of Physiology.... Jun 2022Patients with Parkinson's disease (PD) often suffer from delayed gastric emptying, but the underlying mechanism remains unclear. We have shown previously that a PD rat...
Patients with Parkinson's disease (PD) often suffer from delayed gastric emptying, but the underlying mechanism remains unclear. We have shown previously that a PD rat model comprising bilateral substantia nigra destruction by 6-hydroxydopamine (6-OHDA rats) exhibits gastroparesis with alteration of neural nitric oxide synthase (nNOS) and acetylcholine in gastric corpus. However, changes in pyloric motility in the 6-OHDA rats have not been characterized. Solid gastric emptying test, immunofluorescence, Western blot, and in vitro pyloric motility recordings were used to assess pyloric motor function in the 6-OHDA rats. The 6-OHDA-treated rats displayed delayed solid gastric emptying and a lower basal pyloric motility index. In the 6-OHDA rats, high K-induced transient contractions were weaker in pyloric sphincters. Electric field stimulation (EFS)-induced pyloric sphincter relaxation was lower in the 6-OHDA rats. -nitro-l-arginine methyl ester (l-NAME), a nonselective inhibitor of NOS, markedly inhibited the EFS-induced relaxation in both control and 6-OHDA rats. Pretreatment of tetrodotoxin abolished the effect of EFS on the pyloric motility. In addition, nNOS-positive neurons were extensively distributed in the pyloric myenteric plexus, whereas the number of nNOS-immunoreactive neurons and the protein expression of nNOS were significantly decreased in the pyloric muscularis of 6-OHDA rats. However, sodium nitroprusside-induced pyloric relaxations were similar between the control and 6-OHDA rats. These results indicate that the pyloric sphincters of 6-OHDA rats exhibit both weakened contraction and relaxation. The latter may be due to reduced nNOS in the pyloric myenteric plexus. The dysfunction of the pyloric sphincter might be involved in the delayed gastric emptying. Reduced nitrergic neurons in pyloric myenteric plexus potently contributed to the attenuated relaxation in 6-hydroxydopamine (6-OHDA) rats, subsequently affecting gastric emptying. SNP could well improve the relaxation of pylori in 6-OHDA rats. The present study provides new insight into the diagnosis and treatment of delayed gastric emptying in patients with PD.
Topics: Animals; Gastroparesis; Humans; Nitric Oxide Synthase Type I; Oxidopamine; Parkinson Disease; Pylorus; Rats; Rats, Sprague-Dawley
PubMed: 35380456
DOI: 10.1152/ajpgi.00363.2021 -
Neurogastroenterology and Motility Oct 2022Recent studies with functional endoluminal imaging probe (EndoFLIP ) measure physiologic characteristics of the pylorus. EndoFLIP has the potential to select optimal...
BACKGROUND
Recent studies with functional endoluminal imaging probe (EndoFLIP ) measure physiologic characteristics of the pylorus. EndoFLIP has the potential to select optimal candidates for gastric peroral endoscopic myotomy (G-POEM). Normative values of the pylorus using EndoFLIP have not been established.
METHODS
Twenty-four healthy volunteers (20-56 years old; 15 females) underwent unsedated, transoral EndoFLIP measurements of the pylorus after 8 h of fasting. Measurements of diameter (DM), balloon pressure, and distensibility index (DI) of the pylorus were obtained twice over 5 min at 40, 50, and 60 ml balloon distensions.
KEY RESULTS
Pyloric DM at 40, 50, and 60 ml balloon distensions were 13.0 ± 2.5, 14.3 ± 1.8, and 17.2 ± 2.0 mm, respectively. DM with 60 ml distension was notably higher than with 40 and 50 ml distensions. Pyloric DI at 40, 50, and 60 ml distensions were 10.9 ± 4.8, 11.3 ± 5.8, and 11.1 ± 4.3 mm /mm Hg, respectively (p = 0.86). Linear regression and Bland-Altman plots showed similar distribution of the DM and DI during the second minute compared with the full 5-min measurements at 50 ml distension, as well as between two sequential measurements using 50 ml distension. With 50 ml balloon distension, intraindividual coefficients of variation (COV ) for DM and DI were 13.8% and 29.6%, respectively, and interindividual COV (COV ) were 12.6% and 51.3%, respectively. Similar reproducibility was obtained with 40 ml balloon distension.
CONCLUSIONS AND INFERENCES
Unsedated EndoFLIP can be used to characterize human fasting pyloric diameter and distensibility, with best performance observed with 40 ml and 50 ml distensions and data collection during the second minute. Normative values reported serve as reference values for future studies.
Topics: Adult; Esophageal Achalasia; Esophageal Sphincter, Lower; Fasting; Female; Healthy Volunteers; Humans; Middle Aged; Pylorus; Reproducibility of Results; Young Adult
PubMed: 35468258
DOI: 10.1111/nmo.14386 -
American Journal of Physiology.... Jun 2016Feeding intolerance is a common issue in the care of preterm neonates. The condition manifests as delayed emptying of gastric contents and represents a therapeutic...
Feeding intolerance is a common issue in the care of preterm neonates. The condition manifests as delayed emptying of gastric contents and represents a therapeutic challenge, since the factors accounting for its manifestations are unknown. The main goal of this study was to comparatively investigate the age-related function of rat gastric and pyloric smooth muscle and their putative regulators. We hypothesized that a reduced gastric muscle contraction potential early in life contributes to the delayed gastric emptying of the newborn. Newborn and adult rat gastric (fundus) and pyloric sphincter tissues were comparatively studied in vitro. Shortening of the tissue-specific dissociated smooth muscle cell was evaluated, and expression of the key regulatory proteins Rho-associated kinase 2 and myosin light chain kinase was determined. Gastric and pyloric smooth muscle cell shortening was significantly greater in the adult than the respective newborn counterpart. Expression of myosin light chain kinase and Rho-associated kinase 2 was developmentally regulated and increased with age. Pyloric sphincter muscle expresses a higher neuronal nitric oxide synthase and phosphorylated vasodilator-stimulated phosphoprotein content in newborn than adult tissue. Compared with later in life, the newborn rat gastropyloric muscle has a Ca(2+)-related reduced potential for contraction and the pyloric sphincter relaxation-dependent modulators are overexpressed. To the extent that these rodent data can be extrapolated to humans, the delayed gastric emptying in the newborn reflects reduced stomach muscle contraction potential, as opposed to increased pyloric sphincter tone.
Topics: Animals; Gastric Emptying; Gastric Fundus; Muscle Contraction; Muscle, Smooth; Myosin Light Chains; Nitric Oxide Synthase Type I; Pylorus; Rats; Rats, Sprague-Dawley; rho-Associated Kinases
PubMed: 27125274
DOI: 10.1152/ajpgi.00046.2016 -
American Journal of Physiology.... Nov 2021Multiple theories have been proposed describing the pathogenic mechanisms of ()-associated gastric motility disorders. We assessed ex vivo pyloric activity in -infected...
Multiple theories have been proposed describing the pathogenic mechanisms of ()-associated gastric motility disorders. We assessed ex vivo pyloric activity in -infected rats, and tried to explore the associated ghrelin hormone alteration and pyloric fibrogenesis. In addition, miR-1 was assessed in pyloric tissue samples, being recently accused of having a role in smooth muscle dysfunction. Ninety adult male Wistar albino rats were assigned into nine groups: ) control group, ) sterile broth (vehicle group), ) amoxicillin control, ) omeperazole control, ) clarithromycin control, ) triple therapy control, ) - group, ) -clarithromycin group, and ) -triple therapy group. Urease enzyme activity was applied as an indicator of infection. Ex vivo pyloric contractility was evaluated. Serum ghrelin was assessed, and histological tissue evaluation was performed. Besides, pyloric muscle miR-1 expression was measured. The immunological epithelial to mesenchymal transition (EMT) markers; transforming growth factor β (TGFβ), α-smooth muscle actin (α-SMA), and E-cadherin-3 were also evaluated. By infection, a significant ( < 0.001) reduced pyloric contractility index was recorded. The miR-1 expression was decreased ( < 0.001) in the infected group, associated with reduced serum ghrelin, elevated TGFβ, and α-SMA levels and reduced E-cadherin levels. Decreased miR-1 and disturbed molecular pattern were improved by treatment. In conclusion, infection was associated with reduced miR-1, epithelial to mesenchymal transition, and pyloric hypomotility. The miR-1 may be a target for further studies to assess its possible involvement in -associated pyloric dysfunction, which might help in the management of human manifestations and complications. This work is investigating functional, histopathological, and molecular changes underlying hypomotility and is correlating these with miR-1, whose disturbance is supposed to be involved in smooth muscle dysfunction and cell proliferation according to literature. Epithelial to mesenchymal transition and reduced ghrelin hormone may contribute to infection-associated hypomotility. infection was associated with reduced pyloric miR-1 expression. Targeting miR-1 could be valuable in the clinical management of pyloric hypofunction.
Topics: Actins; Animals; Anti-Bacterial Agents; Cadherins; Disease Models, Animal; Drug Therapy, Combination; Epithelial-Mesenchymal Transition; Gastrointestinal Motility; Ghrelin; Helicobacter Infections; Helicobacter pylori; Male; MicroRNAs; Muscle, Smooth; Proton Pump Inhibitors; Pylorus; Rats, Wistar; Stomach Diseases; Transforming Growth Factor beta; Rats
PubMed: 34431405
DOI: 10.1152/ajpgi.00364.2020 -
Gut and Liver Sep 2022Gastric outlet obstruction (GOO) is a relatively common condition in which mechanical obstruction of the pylorus, distal stomach, or duodenum causes severe symptoms such... (Review)
Review
Gastric outlet obstruction (GOO) is a relatively common condition in which mechanical obstruction of the pylorus, distal stomach, or duodenum causes severe symptoms such as nausea, vomiting, abdominal pain, and early satiety. Its etiology includes both benign and malignant disorders. Currently, GOO has many treatment options, including initial conservative therapeutic protocols and more invasive procedures, such as surgical gastroenterostomy, stent placement and, the most recently implemented procedure, endoscopic ultrasound-guided gastroenterostomy (EUS-GE). Each procedure has its merits, with surgery often prevailing in patients with longer life expectancy and stents being used most often in patients with malignant gastric outlet stenosis. The newly developed EUS-GE combines the immediate effect of stents and the long-term efficacy of gastroenterostomy. However, this novel method is a technically demanding process that requires expert experience and special facilities. Thus, the true clinical effectiveness, as well as the duration of the effects of EUS-GE, still need to be determined.
Topics: Endosonography; Gastric Outlet Obstruction; Gastroenterostomy; Humans; Pylorus; Stents
PubMed: 35314520
DOI: 10.5009/gnl210327 -
Revista Espanola de Enfermedades... Jun 2015
Topics: Aged; Endoscopy, Digestive System; Humans; Male; Pylorus
PubMed: 26031868
DOI: No ID Found -
Biomedical Journal Dec 2022To examine factors that affect the severity of pyloric hypertrophy, post-operative feeding and nutritional recovery in infantile hypertrophic pyloric stenosis (IHPS).
BACKGROUND
To examine factors that affect the severity of pyloric hypertrophy, post-operative feeding and nutritional recovery in infantile hypertrophic pyloric stenosis (IHPS).
METHODS
Medical records of infants diagnosed with IHPS at a single tertiary center between 2009 and 2018 were retrospectively reviewed. Clinical characteristics, biochemistry data and outcome were assessed for their association with the severity of pyloric hypertrophy and post-operative recovery. Nutritional recovery was assessed using weight-for-age status improvement after surgery.
RESULTS
Eighty-five patients were recruited in this study. The mean pre-operative weight-for-age percentile was 18.2. Elevated bicarbonate was positively correlated with symptom duration (p = 0.007). Pyloric muscle thickness was significantly correlated with age, weight, and symptom duration (p = 0.004, 0.003, 0.008, respectively). The mean weight-for-age percentile increased to 41.6 by post-operative weeks 6-8. Pyloric muscle thickness was negatively correlated with nutritional recovery by post-operative weeks 6-8 (p = 0.003). In multivariable analysis, pyloric length related to nutritional recovery at week 1-2 postoperatively (OR = 1.42, p = 0.030, 95% CI = 0.03-1.94), and pyloric muscle thickness related to nutritional recovery at week 6-8 postoperatively (OR = 4.08, p = 0.032, 95% CI = 1.13-14.7).
CONCLUSION
Our study indicated that favorable nutritional outcome and successful weight gain was observed 6-8 weeks after surgery in children with IHPS. Pyloric muscle thickness positively correlated with age, weight, symptom duration, and favorable nutritional recovery. Serum bicarbonate showed a positive correlation with symptom duration.
Topics: Infant; Child; Humans; Pyloric Stenosis, Hypertrophic; Retrospective Studies; Bicarbonates; Pylorus; Hypertrophy
PubMed: 34995820
DOI: 10.1016/j.bj.2021.12.011 -
Revista de Gastroenterologia de Mexico... 2018Pyloric sphincter abnormalities may be detected in gastroparesis. Botulinum toxin A (BoNT/A) injection into the pylorus has been used to treat gastroparesis with varying...
INTRODUCTION AND AIMS
Pyloric sphincter abnormalities may be detected in gastroparesis. Botulinum toxin A (BoNT/A) injection into the pylorus has been used to treat gastroparesis with varying results. The aim of the present article was to assess whether pyloric sphincter characteristics using the endoscopic functional lumen imaging probe (EndoFLIP) with impedance planimetry in patients with gastroparesis correlated with symptoms, gastric emptying, and therapeutic response to pyloric sphincter BoNT/A injection.
METHODS
EndoFLIP study was performed on patients undergoing gastroparesis treatment with BoNT/A. The gastroparesis cardinal symptom index (GCSI) was applied prior to treatment and at post-treatment weeks 2, 4, 8, and 12.
RESULTS
Forty-four patients were enrolled (30 with idiopathic gastroparesis, 14 with diabetic gastroparesis). Smaller pyloric diameter, cross-sectional area (CSA), and distensibility correlated with worse vomiting and retching severity at baseline. Greater gastric retention tended to correlate with decreased CSA and pyloric distensibility. BoNT/A treatment resulted in a significant decrease in the GCSI score at 2 and 4 weeks after treatment, but not at post-treatment weeks 8 or 12. Nausea, early satiety, postprandial fullness, and upper abdominal pain improved up to 12 weeks, whereas loss of appetite, stomach fullness, and stomach visibly larger improved only up to 4 weeks. Retching and vomiting failed to improve. Greater pyloric compliance at baseline correlated with greater improvement in early satiety and náusea at 8 weeks and greater pyloric distensibility correlated with improvement in upper abdominal pain.
CONCLUSIONS
EndoFLIP characteristics of the pylorus provided important pathophysiologic information in patients with gastroparesis, in relation to symptoms, gastric emptying, and predicting the response to treatment directed at the pylorus.
Topics: Adult; Aged; Botulinum Toxins, Type A; Endoscopy, Gastrointestinal; Esophageal Sphincter, Upper; Female; Gastric Emptying; Gastroparesis; Humans; Male; Middle Aged; Pylorus; Treatment Outcome
PubMed: 29709494
DOI: 10.1016/j.rgmx.2018.02.013