The Short-Term Effects and Tolerability of Low-Viscosity Soluble Fibre on Gastroparesis Patients: A Pilot Clinical Intervention Study.

Gastroparesis is a motility disorder that causes severe gastric symptoms and delayed gastric emptying, where the majority of sufferers are females (80%), with 29% of sufferers also diagnosed with Type-1 or Type-2 diabetes. Current clinical recommendations involve stringent dietary restriction and includes the avoidance and minimization of dietary fibre. Dietary fibre lowers the glycaemic index of food, reduces inflammation and provides laxation. Lack of dietary fibre in the diet can affect long-term gastrointestinal health. Our previously published rheological study demonstrated that "low-viscosity" soluble fibres could be a potentially tolerable source of fibre for the gastroparetic population. A randomised controlled crossover pilot clinical study was designed to compare Partially-hydrolysed guar gum or PHGG (test fibre 1), gum Arabic (test fibre 2), psyllium husk (positive control) and water (negative control) in mild-to-moderate symptomatic gastroparesis patients (requiring no enteral tube feeding). The principal aim of the study was to determine the short-term physiological effects and tolerability of the test fibres. In n = 10 female participants, post-prandial blood glucose, gastroparesis symptoms, and breath test measurements were recorded. Normalized clinical data revealed that test fibres PHGG and gum Arabic were able to regulate blood glucose comparable to psyllium husk, while causing far fewer symptoms, equivalent to negative control. The test fibres did not greatly delay mouth-to-caecum transit, though more data is needed. The study data looks promising, and a longer-term study investigating these test fibres is being planned.

New device for active gastric mechanical stimulation.

BACKGROUND: Gastroparesis is a chronic stomach disorder and effective treatment is the aim of different strategies. Alternative therapies consist of an electrical stimulation of the stomach to evoke a response in the gastric activity. We present the development and in vivo application of an electromagnet system to induce a mechanical stimulus in the stomach aiming for gastric contractile responses. METHODS: The electromagnet system consisted of an implantable magnet and an external drive coil. We implanted the magnet at the greater curvature of the gastric body in rats. We applied an alternating current to the drive coils, inducing mechanical stimulation of the gastric wall. We measured the gastric contraction activity and gastric electrical activity in response to the stimulus using AC biosusceptometry and electrogastrography. Moreover, we used the phenol red to evaluate the stimulus effects on gastrointestinal transit. KEY RESULTS: The stimulus increased the spectral intensity and signal-to-noise ratio significantly of gastric contraction activity and gastric electrical activity. Furthermore, we found a lower phenol red retention in the stomach in rats without stimulus. No significant differences were found in frequency and root mean square amplitude. CONCLUSIONS & INFERENCES: We developed a new simple electromagnet system that evoked a contraction and gastric electrical response using a mechanical stimulus and decreased gastric emptying time. The system is an accessible tool and may contribute to gastroparesis studies in animals.

Gastric Electrical Stimulation for Treatment of Refractory Gastroparesis: the Current Approach to Management.

PURPOSE OF REVIEW: Gastroparesis is one of the more challenging entities in the landscape of gastroenterology, posing difficulties for both patients and physicians with regard to effective management and therapies. In this article, we reviewed various gastroparesis treatment options, with an emphasis on gastric electrical stimulation (GES). RECENT FINDINGS: GES has demonstrated a significant reduction of cardinal symptoms in refractory gastroparetic patients, particularly nausea and vomiting, across multiple studies. However, GES has not been shown to conclusively decrease gastric emptying time in these patients. Such finding has led the investigators to analyze the impact of combining GES with pyloroplasty. While this treatment pathway is nascent, its results thus far reveal an amplified improvement of gastroparesis symptomatology in addition to significant reduction of gastric transit, compared to GES by itself. Limited treatment choices are available for refractory gastroparesis. Combining GES with pyloroplasty holds promise but requires further assessment in large-scale trials to fully evaluate the risks and benefits.

Efficacy of gastric electrical stimulation in intractable nausea and vomiting at 10 years: A retrospective analysis of prospectively collected data.

BACKGROUND: Gastric electrical simulation has been shown to relieve nausea and vomiting in medically refractory patients. Efficacy of gastric electrical stimulation has been reported mostly in short-term studies, but none has evaluated its efficacy beyond 10 years after implantation. METHODS: Patients implanted at our center for medically refractory severe and chronic nausea and/or vomiting were evaluated before and over 10 years after implantation using symptomatic scale and quality of life (GIQLI) score. Improvement was defined as a reduction of more than 50% in vomiting frequency. KEY RESULTS: A total of 50 patients were implanted from January 1998 to December 2009. Among them, 7 were explanted due to a lack of efficacy and/or side effects, 2 died, and 4 were lost to follow-up. Mean follow-up was 10.5 ± 3.7 years. In intention-to-treat analysis, 27/50 (54%) patients reported an improvement. Beyond 10 years, an improvement in early satiety (3.05 vs 1.76, <0.001), bloating (2.51 vs 1.70, P = .012), nausea (2.46 vs 1.35, P = .001), and vomiting (3.35 vs 1.49 P < .001) scores were observed. Quality of life improved over 10 years (GIQLI score: 69.7 vs. 86.4, P = .005) and body mass index (BMI: 23.4 vs. 26.2 kg/m2 ; P = .048). CONCLUSIONS AND INFERENCES: Gastric electrical simulation is effective in the long-term in patients with medically refractory nausea and vomiting, with an efficacy of 54% at 10 years on an intention-to-treat analysis. Other long-term observational studies are warranted to confirm these results.

Rheological Characteristics of Soluble Fibres during Chemically Simulated Digestion and their Suitability for Gastroparesis Patients.

Dietary fibres are an integral part of a balanced diet. Consumption of a high-fibre diet confers many physiological and metabolic benefits. However, fibre is generally avoided by individuals with gastrointestinal motility disorders like gastroparesis due to increased likelihood of exacerbated symptoms. Low-viscosity soluble fibres have been identified as a possible source of fibre tolerable for these individuals. The aim of this study is to determine the rheological properties of 10 common commercially available soluble fibres in chemically simulated digestive conditions and evaluate their suitability for individuals with mild to moderate gastroparesis, a gastric motility disorder. Rheological testing under neutral condition (distilled water pH 7) and chemically simulated gastric digestion were evaluated to determine the yield point and relative viscosity of each fibre. Our results reveal two rheological categories of soluble fibres; pseudoplastic and dilatant. Simulated digestion was shown to significantly alter the yield-points of psyllium husk, iota-carrageenan, beta-glucan, apple-fibre pectin, and inulin. Gum Arabic and partially hydrolysed guar gum showed the lowest viscosities and were not affected under simulated digestion, characteristics that make them potential candidate fibres for patients with gastroparesis. Altogether, our results demonstrate that digestion can have a significant impact on fibre viscosity and should be taken into consideration when evaluating the suitability of fibres for patients with gastric motility disorders.

Gastroparesis: New insights into an old disease.

Gastroparesis (Gp) is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction. Although this condition has been reported in the literature since the mid-1900s, only recently has there been renewed clinical and scientific interest in this disease, which has a potentially great impact on the quality of life. The aim of this review is to explore the pathophysiological, diagnostic and therapeutical aspects of Gp according to the most recent evidence. A comprehensive online search for Gp was carried out using MEDLINE and EMBASE. Gp is the result of neuromuscular abnormalities of the gastric motor function. There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes. As regards diagnostic approach, 99-Technetium scintigraphy is currently considered to be the gold standard for Gp. Its limits are a lack of standardization and a mild risk of radiation exposure. The C13 breath testing is a valid and safe alternative method. 13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits. The wireless motility capsule is a promising technique, but its use is limited by costs and scarce availability in many countries. Finally, therapeutic strategies are related to the clinical severity of Gp. In mild and moderate Gp, dietary modification and prokinetic agents are generally sufficient. Metoclopramide is the only drug approved by the Food and Drug Administration for Gp. However, other older and new prokinetics and antiemetics can be considered. As a second-line therapy, tricyclic antidepressants and cannabinoids have been proposed. In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed. In drug-unresponsive Gp patients some alternative strategies (endoscopic, electric stimulation or surgery) are available.

Electroacupuncture Relieves Suppression of Autophagy in Interstitial Cells of Cajal of Diabetic Gastroparesis Rats.

Background: The incidence of diabetic gastroparesis (DGP) is mainly blamed to abnormity of interstitial cells of Cajal (ICCs). Autophagy could degrade damaged proteins and organelles to keep intracellular homeostasis, and it could directly influence structure and number of cells. In this study, we aimed to figure out the relationship between DGP and autophagy of ICCs. Methods: Sixty Sprague-Dawley (SD) rats were randomly divided into normal control group (NC, 10) and modeling group (50). Rats in the modeling group were injected 2% streptozotocin (STZ) and fed with high-glucose and high-fat diet for 8 weeks in order to establish DGP rat model. After modeling, 30 successfully modeled rats were randomly selected and separated into diabetic gastroparesis group (DGP, 10), GDP rats with electroacupuncture group (EA, 10), and GDP rats with metoclopramide group (MP, 10). When the intervention was completed, blood glucose was measured by ONE TOUCH glucometer and gastrointestinal propulsive rate was detected through measuring optical density. Autophagosomes were observed under transmission electron microscope (TEM). The expression of LC3 protein and P62 protein was measured by Western blot. When ICCs were transfected with GFP-RFP-LC3 plasmid, autophagy flux was observed by laser scanning confocal microscope. Results: (1) After intervention, compared with blood glucose of rats in the NC group, all of the DGP, EA, and MP groups were remarkably increased (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01); compared with the DGP group, the blood glucose of the EA and MP groups was decreased greatly (P < 0.01). (2) Compared with gastrointestinal propulsive rate of rats in the NC group, no matter gastric emptying rate or intestinal propulsive rate, the EA and MP groups were significantly reduced (P < 0.01); compared with the NC group, gastric emptying rate and intestinal propulsive rate in the EA group were obviously decreased (P < 0.05, P < 0.01); compared with the DGP group, the EA and MP groups were increased significantly (P < 0.01). (3) Compared with the NC group, intensity of RFP and GFP in the DGP group was obviously increased (P < 0.05, P < 0.01), in other words, the DGP group accompanying suppression of autophagy; compared with the DGP group, intensity of RFP and GFP in the EA group was decreased significantly (P < 0.05, P < 0.01). (4) There was no autophagosome in the NC group, and an autophagosome existed in the DGP group. Both EA and MP groups found autophagy. (5) When coming to LC3 II/LC3 I, compared with the NC group, the ratio was enhanced in the DGP and EA groups (P < 0.01, P < 0.05); compared with the DGP group, LC3 II/LC3 I was dramatically decreased in the MP and EA groups (P < 0.01). (6) As the substrate of degradation, the expression of P62 in the other three groups was significantly increased (P < 0.01) compared with the NC group; compared with the DGP group, the amount of P62 in the EA and MP groups was reduced greatly (P < 0.01). Conclusion: The impaired autophagy flux in ICCs is the pathological basis of diabetic gastroparesis, blaming to fusion dysfunction of autophagosome and lysosome and electroacupuncture (EA) could ease the suppression of autophagy to improve gastric motility.

Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway.

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450-500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway.NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.

Gastric Electrical Stimulation Reduces Refractory Vomiting in a Randomized Crossover Trial.

BACKGROUND & AIMS: There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. We performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis. METHODS: For 4 months, we assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (>12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 µs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary endpoints were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary endpoints were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes. RESULTS: During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; P < .001), in diabetic and nondiabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (P < .01) or normal gastric emptying (P = .05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life. CONCLUSIONS: In a randomized crossover study, we found that GES reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life. Clinicaltrials.gov, Number: NCT00903799.

Safety and Feasibility of Per-Oral Pyloromyotomy as Augmentative Therapy after Prior Gastric Electrical Stimulation for Gastroparesis.

BACKGROUND: For medically refractory diabetic or idiopathic gastroparesis, gastric electrical stimulation (GES) is an excellent option for symptom control; however, a small subset of patients may develop recurrent or persistent symptoms. Per-oral pyloromyotomy (POP, also described by some authors as gastric per-oral endoscopic myotomy or G-POEM) is an emerging therapy for medically refractory gastroparesis. This study investigated the safety and feasibility of POP after previous GES for recurrent or persistent gastroparesis. STUDY DESIGN: We retrospectively identified all patients undergoing POP between January 2016 and December 2017, with GES in situ. Patient characteristics, gastroparesis etiology, and procedural data were collected. Symptoms were assessed with the Gastroparesis Cardinal Symptom Index (GCSI) both before and 30 to 90 days after POP. Standard pre- and post-procedure 4-hour gastric emptying tests were obtained when available. RESULTS: There were 22 patients who met inclusion criteria (81.8% female, mean age 42.3 ± 12.4 years). Causes of gastroparesis were diabetes in 38.1%, and idiopathic in 61.9%. The average time since GES insertion was 3.45 years. Mean preoperative 4-hour gastric retention was 50.1%. Most POP procedures were performed in the operating room (90.9%), with mean operative time of 40 minutes and a 1.4-day length of stay. There were 4 readmissions within 30 days, but no POP-related complications. Overall, GCSI improved by an absolute reduction of 1.63 points (p = 0.002), with significant improvements in all sub-scores. Of 11 patients with post-procedural motility or emptying studies available, 7 were normal. CONCLUSIONS: Per-oral pyloromyotomy appears to be safe and feasible for patients with recurrent gastroparesis symptoms after GES. Both symptoms and motility significantly improved in the short-term. These data replicate similar data suggesting laparoscopic pyloroplasty as an effective augmentative therapy after GES, but may provide a less invasive option for patients.

Drugs under development for the treatment of functional dyspepsia and related disorders.

Introduction: Functional dyspepsia (FD), defined as the presence of chronic functional symptoms originating from the gastroduodenal, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. Therapeutic options for FD are very limited, probably reflecting the complex pathophysiology which comprises disorders of gastric sensorimotor function as well as low-grade duodenal inflammation.Areas covered: This review summarizes recent and ongoing drug development for FD as identifiedExpert opinion: Proton pump inhibitors (PPIs) are the traditional first-line therapy while potassiumcompetitive acid blockers are being studied. Ongoing drug development focuses on gastric motility with prokinetics (dopamine-2 antagonists and 5-HT4 agonists) and fundus relaxant therapies (acotiamide, azapirones), and on sensitivity with peripherally (guanylate cyclase and cannabinoid agonists) and centrally acting neuromodulators. Drugs under development for gastroparesis may be efficacious in PDS. There are emerging data with pro-and antibiotics and with phytotherapeutic agents. Duodenal low-grade inflammation is a newly emerging target which may respond also to PPIs, histamine and leukotriene receptor blockers.

Effectiveness of gastric electrical stimulation in gastroparesis: Results from a large prospectively collected database of national gastroparesis registries.

BACKGROUND: Gastric electrical stimulation (GES) for treating gastroparesis symptoms is controversial. METHODS: We studied 319 idiopathic or diabetic gastroparesis symptom patients from the Gastroparesis Clinical Research Consortium (GpCRC) observational studies: 238 without GES and 81 with GES. We assessed the effects of GES using change in GCSI total score and nausea/vomiting subscales between baseline and 48 weeks. We used propensity score methods to control for imbalances in patient characteristics between comparison groups. KEY RESULTS: GES patients were clinically worse (40% severe vs. 18% for non-GES; P < .001); worse PAGI-QOL (2.2. vs. 2.6; P = .003); and worse GCSI total scores (3.5 vs. 2.8; P < .001). We observed improvements in 48-week GCSI total scores for GES vs. non-GES: improvement by ≥ 1-point (RR = 1.63; 95% CI = (1.14, 2.33); P = .01) and change from enrollment (difference = -0.5 (-0.8, -0.3); P < .001). When adjusting for patient characteristics, symptom scores were smaller and not statistically significant: improvement by ≥ 1-point (RR = 1.29 (0.88, 1.90); P = .20) and change from the enrollment (difference = -0.3 (-0.6, 0.0); P = .07). Of the individual items, the nausea improved by ≥ 1 point (RR = 1.31 (1.03, 1.67); P = .04). Patients with GCSI score ≥ 3.0 tended to improve more than those with score < 3.0. (Adjusted P = 0.02). CONCLUSIONS AND INFERENCES: This multicenter study of gastroparesis patients found significant improvements in gastroparesis symptoms among GES patients. Accounting for imbalances in patient characteristics, only nausea remained significant. Patients with greater symptoms at baseline improved more after GES. A much larger sample of patients is needed to fully evaluate symptomatic responses and to identify patients likely to respond to GES.

Periprocedural Considerations for Patients with Gastric Electrical Stimulators.

OBJECTIVES: Gastric electrical stimulation (GES) is a technology that uses neurostimulation for the modulation of gastric activity. In clinical practice, the most commonly encountered form of GES is high frequency GES. GES devices are typically used for the treatment of refractory gastroparesis, although they have also been investigated for obesity management and the treatment of refractory gastroesophageal reflux disease. Just as many patients with chronic diseases require surgery, patients with an implanted GES device may encounter the need for periprocedural care. Therefore, the purpose of this review is to address the special needs of patients with an implanted GES device. MATERIALS AND METHODS: A systematic computerized search of the literature was performed to consolidate existing knowledge on GES management in the periprocedural setting. Duplicate results were eliminated, and results were further narrowed based on title and abstract. All articles with possible relevance were then reviewed in full. Manufacturer information including pamphlets and websites were also reviewed. RESULTS: A total of 1201 articles were identified for initial review, and 33 met inclusion criteria. CONCLUSIONS: Available data suggests GES is a technology with increasing prevalence. When patients with an implanted GES device present for periprocedural care, the anesthesia staff must consider the device when planning for the procedure. Topics addressed include general anesthetic considerations, nerve localization, radiation exposure, electrocautery, diathermy, emergency external defibrillation, and MRI compatibility.

Gastroparesis syndromes: Response to electrical stimulation.

BACKGROUND AND AIMS: Factors underlying gastroparesis are not well defined, nor is the mechanism of action of gastric electrical stimulation (GES). We hypothesized that GES acts via several mechanisms related to underlying disordered pathophysiology. METHODS: We studied 43 consecutive eligible patients with gastroparetic symptoms, previously evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal; and also categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. We then studied 41 patients who underwent temporary GES for 5-7 days. Thirty-six of those patients were implanted and 30 were followed up at 6 months after permanent GES. RESULTS: In previous but separately reported work, patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status and all patients demonstrated abnormalities in each of the five areas studied. After GES, patients showed early and late effects of electrical stimulation with changes noted in multiple areas, categorized by improvement status. CONCLUSION: Patients with symptoms of gastroparesis have multiple abnormalities, including systemic inflammation and disordered hormonal status. GES affects many of these abnormalities. We conclude electrical stimulation improves symptoms and physiology with (a) an early and sustained anti-emetic effect; (b) an early and durable gastric prokinetic effect in delayed emptying patients; (c) an early anti-arrhythmic effect that continues over time; (d) a late autonomic effect; (e) a late hormonal effect; (f) an early anti-inflammatory effect that persists; and (g) an early and sustained improvement in health-related quality of life. This study is registered with Clinicaltrials.gov under study # NCT03178370 (https://clinicaltrials.gov/ct2/show/NCT03178370).

Pathophysiology of idiopathic gastroparesis and implications for therapy.

OBJECTIVES: Idiopathic gastroparesis is a gastric motility disorder characterized by chronic upper gastrointestinal symptoms and delayed gastric emptying without an identifiable underlying condition. This review summarizes recent understanding of the pathophysiology and treatment of idiopathic gastroparesis. MATERIALS AND METHODS: Structured literature search in the PubMed, Embase and ClinicalTrials.gov databases. RESULTS: Idiopathic gastroparesis involves several alterations in gastric motility and sensation, including delayed gastric emptying, altered myoelectrical activity, impaired fundic accommodation, visceral hypersensitivity and disturbances in antropyloroduodenal motility and coordination. Multiple cellular changes have been identified, including depletion of interstitial cells of Cajal (ICC) and enteric nerves, as well as stromal fibrosis. The underlying cause of these changes is not fully understood but may be an immune imbalance, including loss of anti-inflammatory heme-oxygenase-1 positive (HO-1) macrophages. There is currently no causal therapy for idiopathic gastroparesis. The treatment ladder consists of dietary measures, prokinetic and antiemetic medications, and varying surgical or endoscopic interventions, including promising pyloric therapies. There are ongoing trials with several novel medications, raising hopes for future treatment. CONCLUSIONS: Patients with idiopathic gastroparesis present several pathophysiological alterations in the stomach, where depletion of ICC is of special importance. Treatment is currently focused on alleviating symptoms through dietary adjustments, medication or surgical or endoscopic interventions.

The Effect of Gastric Electrical Stimulation on Small Bowel Motility in Patients With Gastroparesis and Concomitant Pancreatic and Small Bowel Dysfunction: From Animal Model to Human Application.

BACKGROUND/AIMS: Patients with gastroparesis often have biliary/pancreatic and small bowel symptoms but the effects of gastric electrical stimulation on small bowel electrical activity of the mid-gut have not been studied. Animal model aim: Establish gastric and upper small bowel/biliary slow wave activity relationships with electrical stimulation. Human study aim: Demonstrate improvement in symptoms associated with proximal small bowel dysmotility in gastric stimulated patients. MATERIALS AND METHODS: Animal model: In vivo evoked responses of duodenal and Sphincter of Oddi measures recorded during gastric electrical stimulation in a nonsurvival swine model (N = 3). High-resolution electrical slow wave mapping of frequency, amplitude, and their ratio, for duodenal and Sphincter of Oddi electrical activity were recorded. Human study: Patients (N = 8) underwent temporary gastric stimulation with small bowel electrodes. Subjective and objective data was collected before and after temporary gastric stimulation. Symptom scores, gastric emptying times, and mucosal electrograms via low-resolution mapping were recorded. RESULTS: Animal gastric stimulation resulted in some changes in electrical activity parameters, especially with the highest energies delivered but the changes were not statistically significant. Human study revealed improvement in symptom and illness severity scores, and changes in small bowel mucosal slow wave activity. CONCLUSIONS: Gastric electrical stimulation in an animal model seems to show nonsignificant effects small bowel slow wave activity and myoelectric signaling, suggesting the existence of intrinsic neural connections. Human data shows more significance, with possible potential for therapeutic use of electrical stimulation in patients with gastroparesis and pancreato-biliary and small bowel symptoms of the mid-gut. This study was limited by the nonsurvival pig model, small sample size, and open label human study.

Gastric Electrical Stimulator for Treatment of Gastroparesis.

Patients with gastroparesis sometimes suffer from intractable nausea and vomiting, abdominal pain, and bloating, as well as a host of other symptoms that can often be difficult to control. Initially, patients are treated conservatively; some do well with conservative management but unfortunately some do not. Over the years, studies have shown the benefits of gastric electrical stimulation, which often results in symptomatic improvement and improvement in gastric emptying times. This article discusses the history of gastric electrical stimulation and its use in clinical practice to help those suffering from gastroparesis that is refractory to conservative medical management.

Gastric electrical stimulation: An emerging therapy for children with intractable gastroparesis.

Management of gastroparesis remains challenging, particularly in pediatric patients. Supportive care and pharmacological therapies for symptoms remain the mainstay treatment. Although they are effective for mild and some moderately severe cases, often time they do not work for severe gastroparesis. There are a few prokinetics available, yet the use of these drugs is limited by a lack of persistent efficacy and/or safety concerns. Currently, the only modality for adult patients with severe intractable gastroparesis is surgery, e.g., pyloroplasty and partial gastrectomy, however, this option is generally considered too radical for a growing child. Novel therapeutic approaches, particularly those which are less invasive, are needed. This article explores gastric electrical stimulation (GES), a new therapy for gastroparesis. Unlike others, it neither needs medications nor gastrectomy; rather, it treats through the use of microelectrodes to deliver high-frequency low energy electric stimulation to the pacemaker area of the stomach. Thus, it is tolerated and safe in children. Like in adult patients, GES appears to work in releasing symptoms, improving nutrition, and enhancing the quality of life; it also helps wean off medications and eliminate many needs for hospitalization. Considering the transient nature of gastroparesis in children in many occasions, GES is considered a "bridging" therapy after failed medical interventions and before surgery.

Minimally-invasive temporary gastric stimulation: A pilot study to predict the outcome of electronic gastric stimulation with the Enterra™ system.

INTRODUCTION: Gastroparesis (GP) is defined as delayed gastric emptying (GE) without any obstruction of the pylorus. It can be divided into idiopathic, diabetic, post surgical and rare causes. Electronic gastric stimulation (EGS) - Enterra Medtronic™ - is a part of GP therapy. Although its positive impact has been reported in open label trials, randomized controlled trials failed in demonstrating a positive outcome. The aim of this pilot study was to establish a reliable prediction for permanent gastric stimulation. PATIENTS AND PROCEDURE: 6 female patients underwent laparoscopic implantation of 2 temporary electrodes. The Enterra™ system was connected and taped to the skin. Baseline and postoperative gastroparesis cardinal symptom index (GCSI), a validated index for GP therapy, was assessed. Response to EGS was defined as a 50% decrease of baseline GCSI. RESULTS: 4 of 6 patients responded to temporary EGS. 3 of 4 responders underwent permanent implantation. 1 non-responder received a permanent Enterra™ at another institution. After a median follow up time of 9months the responder group GCSI remained low, whereas the non-responder GCSI had increased. Moreover, the health care system was saved € 30,678.03 by this test stimulation concept. CONCLUSION: Laparoscopic implantation of a temporary EGS system predicts the outcome of permanent gastric stimulation and is cost-saving.