The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of ...gastroparesis.
Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models.
Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls.
A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly “organic” gastric neuromuscular disorders.
NCT00398801, NCT01696747
Background
Pyloric dysfunction has been associated with gastroparesis, particularly diabetic gastroparesis. Endoscopic functional luminal imaging probe (EndoFLIP) uses 16 sensors inside a balloon ...that is inflated inside a sphincter to assess physiologic characteristics. The aim of this study was to measure the pressure, diameter, cross‐sectional area (CSA), and distensibility of the pylorus using EndoFLIP in patients with gastroparesis. In addition, the relationship between pyloric pathophysiology with gastroparesis etiology, symptoms, and gastric emptying was assessed.
Methods
EndoFLIP was performed in 54 patients (39 idiopathic gastroparesis, 15 diabetic gastroparesis). The EndoFLIP catheter was passed endoscopically so that the balloon straddled the pylorus. Pressure, diameter, CSA, and distensibility of the pylorus were measured at 20, 30, 40, and 50 cc balloon volume.
Key Results
Pyloric sphincter contour was seen best at 40 cc balloon distension (diameter 12.2 ± 0.44 mm, CSA 125.2 ± 9.15 mm2, pressure 18.0 ± 1.23 mmHg, length 1.59 ± 0.34 cm, distensibility 10.7 ± 2.57 mm2/mmHg). There was a wide range seen in diameter (5.6–22.1 mm) and distensibility (1–55 mm2/mmHg) of the pylorus. Symptoms of early satiety and postprandial fullness were inversely correlated with pyloric sphincter diameter and CSA. No significant difference was seen between diabetic and idiopathic gastroparetics.
Conclusions & Inferences
EndoFLIP is a novel technique that can be used to assess pyloric physiologic characteristics. Early satiety and postprandial fullness were inversely correlated with diameter and CSA of the pyloric sphincter. No significant differences were seen comparing diabetic and idiopathic gastroparetics. This technology may be of benefit to help select patients with pyloric sphincter abnormalities.
EndoFLIP is a novel technique that can be used to assess pyloric physiologic characteristics. Early satiety and postprandial fullness were inversely correlated with diameter and CSA of the pyloric sphincter. No significant differences were seen comparing diabetic and idiopathic gastroparetics. This technology may be of benefit to help select patients with pyloric sphincter abnormalities for therapies aimed at the pylorus.
Gastroparesis is characterized by delayed gastric emptying and symptoms thereof in the absence of gastric outlet obstruction. Most studies on the epidemiology of gastroparesis have been conducted in ...selected case series rather than in the population at large. In the only community-based study of gastroparesis in diabetes mellitus (DM), the average cumulative incidence of symptoms and delayed gastric emptying over 10 years was higher in type 1 DM (5%) than in type 2 DM (1%) and controls (1%). In the United States, the incidence of hospitalizations related to gastroparesis increased substantially between 1995 and 2004, and particularly after 2000.
Recent evidence of the significant impact of gastroparesis on morbidity and mortality mandates optimized management of this condition. Gastroparesis affects nutritional state, and in diabetics it has ...deleterious effects on glycemic control and secondary effects on organs that increase mortality. First-line treatments include restoration of nutrition and medications (prokinetic and antiemetic). We review the epidemiology, pathophysiology, impact, natural history, time trends, and treatment of gastroparesis, focusing on diabetic gastroparesis. We discuss pros and cons of current treatment options, including metoclopramide. Second-line therapeutic approaches include surgery, venting gastrostomy or jejunostomy, and gastric electrical stimulation; most of these were developed based on results from open-label trials. New therapeutic strategies for gastroparesis include drugs that target the underlying defects, prokinetic agents such as 5-hydroxytryptamine agonists that do not appear to have cardiac or vascular effects, ghrelin agonists, approaches to pace the stomach, and stem cell therapies.
Gastroparesis Camilleri, Michael; Sanders, Kenton M.
Gastroenterology (New York, N.Y. 1943),
01/2022, Letnik:
162, Številka:
1
Journal Article
Recenzirano
Odprti dostop
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.
Abdominal pain can be an important symptom in some patients with gastroparesis (Gp).
Aims
(1) To describe characteristics of abdominal pain in Gp; (2) describe Gp patients reporting abdominal pain.
...Methods
Patients with idiopathic gastroparesis (IG) and diabetic gastroparesis (DG) were studied with gastric emptying scintigraphy, water load test, wireless motility capsule, and questionnaires assessing symptoms Patient Assessment of Upper GI Symptoms (PAGI-SYM) including Gastroparesis Cardinal Symptom Index (GCSI), quality of life (PAGI-QOL, SF-36), psychological state Beck Depression Inventory (BDI), State-Trait Anxiety Index (STAI), PHQ-15 somatization scale.
Results
In total, 346 Gp patients included 212 IG and 134 DG. Ninety percentage of Gp patients reported abdominal pain (89% DG and 91% IG). Pain was primarily in upper or central midline abdomen, described as cramping or sickening. Upper abdominal pain was severe or very severe on PAGI-SYM by 116/346 (34%) patients, more often by females than by males, but similarly in IG and DG. Increased upper abdominal pain severity was associated with increased severity of the nine GCSI symptoms, depression on BDI, anxiety on STAI, somatization on PHQ-15, the use of opiate medications, decreased SF-36 physical component, and PAGI-QOL, but not related to severity of delayed gastric emptying or water load ingestion. Using logistic regression, severe/very severe upper abdominal pain associated with increased GCSI scores, opiate medication use, and PHQ-15 somatic symptom scores.
Conclusions
Abdominal pain is common in patients with Gp, both IG and DG. Severe/very severe upper abdominal pain occurred in 34% of Gp patients and associated with other Gp symptoms, somatization, and opiate medication use.
ClinicalTrials.gov Identifier: NCT01696747.
Gastroparesis is defined by delayed gastric emptying (GE) and symptoms of nausea, vomiting, bloating, postprandial fullness, early satiety and abdominal pain. Most common aetiologies include ...diabetes, postsurgical and postinfectious, but in many cases it is idiopathic. Clinical presentation and natural history vary by the aetiology. There is significant morbidity and healthcare utilisation associated with gastroparesis. Mechanistic studies from diabetic animal models of delayed GE as well as human full-thickness biopsies have significantly advanced our understanding of this disorder. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system through paracrine and oxidative stress mediators is likely central to the pathogenesis of gastroparesis. Scintigraphy and
C breath testing provide the most validated assessment of GE. The stagnant gastroparesis therapeutic landscape is likely to soon see significant changes. Relatively newer treatment strategies include antiemetics (aprepitant), prokinetics (prucalopride, relamorelin) and fundic relaxants (acotiamide, buspirone). Endoscopic pyloromyotomy appears promising over the short term, especially for symptoms of nausea and vomiting. Further controlled trials and identification of the appropriate subgroup with pyloric dysfunction and assessment of long-term outcomes are essential. This review highlights the clinical presentation, diagnosis, mechanisms and treatment advancements for gastroparesis.
DIABETIC GASTROPARESIS Bharucha, Adil E; Kudva, Yogish C; Prichard, David O
Endocrine reviews,
10/2019, Letnik:
40, Številka:
5
Journal Article
Recenzirano
Odprti dostop
This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the ...gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.
Interstitial cells of Cajal (ICCs) and pancreatic β cells require receptor tyrosine kinase (KIT) to develop and function properly. Degeneration of ICCs is linked to diabetic gastroparesis. The ...mechanisms linking diabetes and gastroparesis are unclear, but may involve microRNA (miRNA)-mediated post-transcriptional gene silencing in KIT+ cells.
We performed miRNA-sequencing analysis from isolated ICCs in diabetic mice and plasma from patients with idiopathic and diabetic gastroparesis. miR-10b-5p target genes were identified and validated in mouse and human cell lines. For loss-of-function studies, we used KIT+ cell-restricted mir-10b knockout mice and KIT+ cell depletion mice. For gain-of-function studies, a synthetic miR-10b-5p mimic was injected in multiple diabetic mouse models. We compared the efficacy of miR-10b-5p mimic treatment vs antidiabetic and prokinetic medicines.
miR-10b-5p is highly expressed in ICCs from healthy mice, but drastically depleted in ICCs from diabetic mice. A conditional knockout of mir-10b in KIT+ cells or depletion of KIT+ cells in mice leads to degeneration of β cells and ICCs, resulting in diabetes and gastroparesis. miR-10b-5p targets the transcription factor Krüppel-like factor 11 (KLF11), which negatively regulates KIT expression. The miR-10b-5p mimic or Klf11 small interfering RNAs injected into mir-10b knockout mice, diet-induced diabetic mice, and TALLYHO polygenic diabetic mice rescue the diabetes and gastroparesis phenotype for an extended period of time. Furthermore, the miR-10b-5p mimic is more effective in improving glucose homoeostasis and gastrointestinal motility compared with common antidiabetic and prokinetic medications.
miR-10b-5p is a key regulator in diabetes and gastrointestinal dysmotility via the KLF11-KIT pathway. Restoration of miR-10b-5p may provide therapeutic benefits for these disorders.
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ACG Clinical Guideline: Gastroparesis Camilleri, Michael; Kuo, Braden; Nguyen, Linda ...
The American journal of gastroenterology,
08/2022, Letnik:
117, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Gastroparesis is characterized by symptoms suggesting retention of food in the stomach with objective evidence of delayed gastric emptying in the absence of mechanical obstruction in the gastric ...outflow. This condition is increasingly encountered in clinical practice. These guidelines summarize perspectives on the risk factors, diagnosis, and management of gastroparesis in adults (including dietary, pharmacological, device, and interventions directed at the pylorus), and they represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation process. When the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.
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