Difference in Cyclic Versus Non-cyclic Symptom Patterns in Patients with the Symptoms of Gastroparesis Undergoing Bioelectric Therapy.

INTRODUCTION: Patients with gastroparesis (Gp) have symptoms with or without a cyclic pattern. This retrospective study evaluates differences in cyclic vs. non-cyclic symptoms of Gp by analyzing mucosal electrogastrogram (mEG), familial dysautonomias, and response to gastric stimulation. METHODS: 37 patients with drug refractory Gp, 7 male and 30 female, with a mean age of 41.4 years, were studied. 18 had diabetes mellitus, 25 had cyclic (Cyc), and 12 had a non-cyclic (NoCyc) pattern of symptoms. Patients underwent temporary mucosal gastric stimulator (tGES) placement, which was done as a trial before permanent stimulator (GES) placement. Electrogastrogram (EGG) by mucosal (mEG) measures, including frequency, amplitude, and frequency-amplitude ratio (FAR), were pre- and post-tGES. Patients' history of personal and familial dysautonomias, quality of life, and symptom scores were recorded. Baseline vs. follow-ups were compared by paired t tests and McNemar's tests. T tests contrasted symptom scores, gastric emptying tests (GET), and mEG measures, while chi-squared tests deciphered comorbidity differences between two groups and univariate and multivariate analyses. RESULTS: There were significantly more patients with diabetes in the Cyc group vs. the NoCyc group. Using a 1 point in symptom outcome, 18 patients did not improve and 19 did improve with tGES. Using univariable analysis, with the cyclic pattern as a predictor, patients exhibiting a cyclic pattern had an odds ratio of 0.22 (95% CI 0.05-0.81, p = 0.054) for achieving an improvement of at least one unit in vomiting at follow-up from baseline. The mucosal electrogastrogram frequency to amplitude ratio (FAR) for the "not Improved" group was 19.6 [3.5, 33.6], whereas, for the "Improved" group, it was 54.3 [25.6, 72.5] with a p-value of 0.049. For multivariate logistic regression, accounting for sex and age squared, patients exhibiting a cyclic pattern had an adjusted odds ratio (OR) of 0.16 (95% CI 0.03-0.81, p = 0.027) for achieving an improvement of at least one unit in vomiting at follow-up from baseline. The two groups had no significant differences in the personal or inherited history of investigated familial patterns. CONCLUSION: This study shows differences in Gp patients with Cyc vs. NoCyc symptoms in several areas. Larger studies are needed to elicit further differences between the two groups about cycles of symptoms, EGG, findings, familial patterns, and response to mucosal GES.

Impact of Gastric Electrical Stimulation on Economic Burden of Refractory Vomiting: A French Nationwide Multicentre Study.

BACKGROUND & AIMS: Medico-economic data of patients suffering from chronic nausea and vomiting are lacking. In these patients, gastric electrical stimulation (GES) is an effective, but costly treatment. The aim of this study was to assess the efficacy, safety and medico-economic impact of Enterra therapy in patients with chronic medically refractory nausea and vomiting. METHODS: Data were collected prospectively from patients with medically refractory nausea and/or vomiting, implanted with an Enterra device and followed for two years. Gastrointestinal quality of life index (GIQLI) score, vomiting frequency, nutritional status and safety were evaluated. Direct and indirect expenditure data were prospectively collected in diaries. RESULTS: Complete clinical data were available for142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic), 24 months after implantation. GIQLI score increased by 12.1 ± 25.0 points (p < .001), with a more significant improvement in non-diabetic than in diabetic patients (+15.8 ± 25.0 points, p < .001 versus 7.3 ± 24.5 points, p = .027, respectively). The proportion of patients vomiting less than once per month increased by 25.5% (p < .001). Hospitalisations, time off work and transport were the main sources of costs. Enterra therapy decreased mean overall healthcare costs from 8873 US$ to 5525 US$ /patient/year (p = .001), representing a saving of 3348 US$ per patient and per year. Savings were greater for diabetic patients (4096 US$ /patient/year) than for non-diabetic patients (2900 US$ /patient/year). CONCLUSIONS: Enterra therapy is an effective, safe and cost-effective option for patients with refractory nausea and vomiting. CLINICALTRIALS: gov Identifier: NCT00903799.

Impact of adaptive gastric electrical stimulation on weight, food intake, and food intake rate in dogs.

BACKGROUND: Gastric electrical stimulation (GES) has been studied for decades as a promising treatment for obesity. Stimulation pulses with fixed amplitude and pulse width are usually applied, but these have limitations with regard to overcoming habituation to GES and inter-subject variation. This study aims to analyze the efficacy of an adaptive GES protocol for reducing food intake and maintaining lean weight in dogs. METHODS: Six beagle dogs were implanted with a remotely programmable gastric stimulator. An adaptive protocol was designed to increase the stimulation energy proportionally to the excess of food consumption, with respect to the dogs' maintenance energy requirements. After surgery and habituation to experimental conditions, the dogs went through both a control and a stimulation period of 4 weeks each, in a randomized order. The stimulation parameters were adapted daily. Body weight, food intake, food intake rate, and postprandial cutaneous electrogastrograms (EGG) were recorded to assess the effect of adaptive GES. RESULTS: Adaptive GES decreased food intake and food intake rate (p < 0.05) resulting in weight maintenance. In the absence of GES, the dogs gained weight (p < 0.05). Postprandial EGG dominant frequency was accelerated by GES (p < 0.05). The strategy of adapting the stimulation energy was effective in causing significant mid-term changes. CONCLUSION: Adaptive GES is effective for reducing food intake and maintaining lean weight. The proposed adaptive strategy may offer benefits to counter habituation and adapt to inter-subject variation in clinical use of GES for obesity.

Low-Resolution Electrogastrogram at Baseline and Response to Temporary Gastric Electrical Stimulation-A Comparison of Cutaneous With Mucosal Recordings.

INTRODUCTION: Gastric electrical stimulation (GES) is a widely accepted therapy for gastroparesis symptoms, but how a brief cutaneous electrogastrogram (EGG) can be used in conjunction with GES has not been well defined. We evaluated the clinical importance of EGG, its correlation with mucosal electrograms (mEGs), gastric emptying tests (GETs), and gastrointestinal symptoms before and after temporary GES (tGES). MATERIALS AND METHODS: We studied 1345 patients; 991 had complete data. EGG measurements like frequency and amplitude were recorded at baseline and five days post-tGES using short recording periods. A total of 266 participants having additional cutaneous propagation values were separately analyzed. Patients underwent solid GET before and after tGES and self-reported symptoms using standardized traditional patient-reported outcomes (TradPRO) scores. Pearson correlations were assessed at baseline, post-stimulation, and their changes over the follow-up period. RESULTS: EGG measures correlated with symptoms and GET results. Patients with abnormal baseline cutaneous frequency had higher baseline total symptom scores (p < 0.003). Post-tGES, one-hour gastric emptying was significantly changed (p < 0.0001) and was mainly observed with abnormal baseline cutaneous frequencies (p < 0.0001). Cutaneous frequency significantly increased after tGES (p < 0.0001), correlating positively with TradPRO scores and one-hour gastric emptying. Mucosal and cutaneous measures correlated pre- and post-treatment. Of the 266 patients, 153 changed propagation states between baseline and temporary; changing states from lower at baseline to higher at temporary was more likely than vice versa. Short EGG recording times can demonstrate changes after the bioelectric therapy of GES. CONCLUSION: EGG is valuable in the diagnosis of delayed gastric emptying and comparable with mEG. It is less invasive and can identify patients who may require GES. Frequency, amplitude, their ratio (frequency-amplitude ratio), and propagation appear to be reliable measures of EGG. EGG provides cost-effective measurement of electrophysiological properties and significantly correlates with important clinical measures. Shorter EGG recording times may be adequate to see changes from bioelectric therapies. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03876288.

Gastric Electrical Stimulation for the Treatment of Gastroparesis or Gastroparesis-like Symptoms: A Systemic Review and Meta-analysis.

BACKGROUND: The effects of gastric electrical stimulation are not fully understood. We aimed to assess the efficacy of gastric electrical stimulation (GES) for patients with gastroparesis and gastroparesis-like symptoms. MATERIALS AND METHODS: We searched PubMed, Scopus, Cochrane, Web of Science, Embase, and Science Direct to identify controlled trials and cohort studies. We used random effects models to estimate pooled effects. A total of nine studies met the criteria and were included for the final qualitative synthesis and the quantitative analysis. We examined the mean absolute differences (MD) and 95% CIs. RESULTS: Nine studies (n = 730) met the criteria and were included for the final qualitative synthesis and the quantitative analysis. There was significant improvement in gastrointestinal (GI) total symptom score (TSS) with the GES group compared with controls during the randomized blind trials. This effect was sustained at 12 months after treatment compared with before treatment (MD = -6.07; 95% CI, -4.5 to -7.65; p < 0.00001). The pooled effect estimate showed a significant improvement in frequency of weekly vomiting episodes at 12 months compared with before treatment (MD = -15.59; 95% CI, -10.29 to -20.9; p < 0.00001). CONCLUSION: GES appears beneficial, with significant improvement in GI TSS, weekly vomiting frequency, gastric emptying study, and quality of life.

Gastric Electrical Stimulation Increases the Proliferation of Interstitial Cells of Cajal and Alters the Enteric Nervous System in Diabetic Rats.

BACKGROUND: Lack of interstitial cells of Cajal (ICC) and neuropathy were the most possible pathological mechanisms of diabetic gastroparesis. Gastric electrical stimulation (GES) is a promising way to treat gastroparesis. This study aimed to explore the impact of GES on ICC together with enteric neurons in diabetic rats and the possible mechanisms involved. MATERIALS AND METHODS: A total of 60 rats were randomized into six groups, including the normal control group, diabetic group (DM), diabetic with sham GES group (DM + SGES), and three groups of diabetic rats with GES (DM + GES1, DM + GES2, and DM + GES3). The proliferation of ICC and expressions of 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5, and glia cell line-derived neurotrophic factor (GDNF) in the antrum of the stomach were evaluated by immunofluorescence staining or Western blot. The levels of 5-HT in blood and tissue were determined by enzyme-linked immunosorbent assay. RESULTS: The proliferation of ICC was significantly reduced in the DM group, together with the DM + SGES group, but increased in the three DM + GES groups. The expression of 5-HT2B was decreased in the DM group and enhanced in the DM + GES groups. Similarly, the levels of 5-HT in the blood and distal stomach tissue were increased in the DM + GES groups. Both nNOS labeled neurons and CHAT-positive neurons were reduced in the myenteric plexus of the DM group, whereas these neurons were dramatically increased the in DM + GES groups. The expression of GDNF protein in the diabetic rats was down-regulated, whereas GES increased the expression of GDNF. CONCLUSIONS: GES improves the proliferation of ICC possibly related with the 5-HT/5-HT2B signal pathway and alters the enteric nervous system partly though the GDNF expression.

Stomach region stimulated determines effects on duodenal motility in rats.

Gastric electrical stimulation (GES) is used clinically to promote proximal GI emptying and motility. In acute experiments, we measured duodenal motor responses elicited by GES applied at 141 randomly chosen electrode sites on the stomach serosal surface. Overnight-fasted (H2O available) anesthetized male rats (n = 81) received intermittent biphasic GES for 5 min (20-s-on/40-s-off cycles; I = 0.3 mA; pw = 0.2 ms; 10 Hz). A strain gauge on the serosal surface of the proximal duodenum of each animal was used to evaluate baseline motor activity and the effect of GES. Using ratios of time blocks compared with a 15-min prestimulation baseline, we evaluated the effects of the 5-min stimulation on concurrent activity, on the 10 min immediately after the stimulation, and on the 15-min period beginning with the onset of stimulation. We mapped the magnitude of the duodenal response (three different motility indices) elicited from the 141 stomach sites. Post hoc electrode site maps associated with duodenal responses suggested three zones similar to the classic regions of forestomach, corpus, and antrum. Maximal excitatory duodenal motor responses were elicited from forestomach sites, whereas inhibitory responses occurred with stimulation of the corpus. Moderate excitatory duodenal responses occurred with stimulation of the antrum. Complex, weak inhibitory/excitatory responses were produced by stimulation at boundaries between stomach regions. Patterns of GES efficacies coincided with distributions of previously mapped vagal afferents, suggesting that excitation of the duodenum is strongest when GES electrodes are situated over stomach concentrations of vagal intramuscular arrays, putative stretch receptors in the muscle wall.

Afferent vagal stimulation via gastric electrical stimulation alters sympathetic-vagal balance in domestic pigs - a pilot trial.

The disturbance of the sympathetic-vagal balance with increasing sympathetic activity and consecutive increase in cytokine release is a major threat in numerous hyperinflammatory syndromes. Therapeutic interventions that modulate the activity in the sympathetic-vagal system are suggested as an effective treatment in these incidences. The purpose of this pilot study was to investigate the effect of electrical stimulation of the gastric wall on sympathetic-vagal balance. German domestic pigs (n=5) were prepared with a modified gastric tube (mGT) for repetitive gastric electrical stimulation (GES). Electrocardiogram was recorded continuously and heart rate variability (HRV) as measure of sympathetic-vagal activity was calculated for three-minute epochs at baseline condition before GES and during GES condition. In comparison to baseline, activity of the autonomic nervous system (ANS) shifted significantly toward increased dominance of vagal activity during GES with a decrease of normalized low frequency (nLF from 58.00 to 25.52) as marker of sympathetic dominance and parallel increase of normalized high frequency (nHF from 41.48 to 74.16) as marker of vagal dominance. During GES, compared to baseline, no difference in heart rate was found. These results indicate that electrical stimulation of the gastric wall may result in shifting the sympathetic-vagal balance toward a parasympathetic predominance.

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.

Does etiology of gastroparesis determine clinical outcomes in gastric electrical stimulation treatment of gastroparesis?

BACKGROUND: Gastroparesis is a condition characterized by impaired gastric motility that may result in weight loss and malnutrition. There have been promising studies demonstrating improvement in symptoms after gastric electrical stimulation (GES) implantation for medically refractory gastroparetics [1-10]. With the heterogeneous population of gastroparetics, the aim of this study was to assess if etiology correlated with response to GES. METHODS: A retrospective review and analysis was performed on patients who underwent GES over a 10-year period at a single institution. Each patient was stratified into an etiological subset (diabetes, idiopathic, post-surgical). Patients were compared by demographics, medical and surgical history, subsequent GES explantation vs continued therapy, need for supplemental nutrition postoperatively, weight gain, weight loss or weight maintenance, and readmission rates. RESULTS: 183 patients underwent GES from 2005 to 2015. 50% were diabetic (n = 91), 42% idiopathic (n = 76), and 9% post-surgical (n = 16). Diabetic patients (DM) demonstrated the highest likelihood of continued therapy compared to post-surgical (PS) and idiopathic patients (ID) (54.7% vs 9.5% vs 35.8%, respectively, p < 0.05). DM patients saw a greater incidence of weight gain > 4 kg, compared to PS and IS patients (67.6% vs 8.1% vs. 24.3%, respectively, p < 0.05). ID patients were most likely to have it removed compared to DM and PS patients (65.7% vs 28.6% vs 5.7%, respectively, p = < 0.05). PS patients were least likely to have their GES removed. They were also least likely to utilize supplemental nutrition compared to DM and ID (9.4% vs 49.1% vs 41.51%, respectively, p < 0.05). CONCLUSIONS: Patients with gastroparesis had different clinical outcomes after GES therapy based on underlying etiology. By gaining a better understanding of the effects of GES, it can be offered to the appropriate patient.

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.

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.

In Vivo Validation of a Less Invasive Gastrostimulator.

Gastrointestinal stimulator implants have recently shown promising results in helping obese patients lose weight. However, to place the implant, the patient currently needs to undergo an invasive surgical procedure. We report a less invasive procedure to stimulate the stomach with a gastrostimulator. After attempting fully endoscopic implantation, we more recently focused on a single incision percutaneous procedure. In both cases, the challenges in electronic design of the implant are largely similar. This article covers the work achieved to meet these and details the in vivo validation of a gastrostimulator aimed to be endoscopically placed and anchored to the stomach.

Gastrointestinal Peptides During Chronic Gastric Electrical Stimulation in Patients With Intractable Vomiting.

OBJECTIVES: Gastric electrical stimulation (GES) is an alternative therapy to treat patients with intractable vomiting. A preclinical study has demonstrated the modulation of the gastrointestinal (GI) peptide ghrelin by GES but such mechanism has never been investigated in patients. The aim of this work was to assess the effect of GES on GI peptide levels in patients with intractable vomiting. MATERIALS AND METHODS: Twenty-one patients were randomized to receive either ON or OFF GES, 14 completed the study (10 ON, 4 OFF stimulation). Vomiting episodes, gastric emptying, and gastrointestinal quality of life index (GIQLI) were assessed. Gastric and blood samples were collected before and four months after the ON period of gastric stimulation. mRNA and/or peptide levels were assessed in gastric biopsies for ghrelin, leptin, and NUCB2/nesfatin-1 and in duodenal biopsies for glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) using RT-qPCR and multiplex technology. Ghrelin, leptin, GLP-1, PYY, gastric inhibitory peptide (GIP), and NUCB2/nesfatin-1 levels also were quantified in blood samples. RESULTS: Among clinical parameters, vomiting episodes were slightly reduced by GES (p = 0.09). In tissue, mRNA or protein levels were not modified following chronic GES. In blood, a significant reduction of postprandial PYY levels (p < 0.05) was observed at M4 and a reduction of NUCB2/nesfatin-1 levels in fasted patients (p < 0.05). Increased plasma leptin levels after GES were correlated with reduction of vomiting and improvement of GIQLI. CONCLUSIONS: GES reduces NUCB2/nesfatin-1 levels under fasting conditions and postprandial PYY levels in patients suffering from nausea and/or vomiting refractory to pharmacological therapies.

Treatment of gastrointestinal autonomic neuropathy.

The symptoms caused by gastrointestinal autonomic neuropathy in diabetes mellitus is important to highlight since it affects a large proportion of people with diabetes, regardless of whether this is type 1 or type 2. Gastroparesis and general signs of bowel dysfunction, such as constipation, diarrhoea and abdominal pain are most often encountered and involve both pharmacological and non-pharmacological treatment options. This mini-review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Azpiroz and Malagelada, DOI: 10.1007/s00125-015-3831-1 ) and a commentary by the Session Chair, Péter Kempler (DOI: 10.1007/s00125-015-3826-y ).

Interventional treatment of obesity and diabetes: An interim report on gastric electrical stimulation.

Gastric electrical stimulation has been applied to treat human obesity since 1995. Dilatation of the stomach causes a series of neural reflexes which result in satiation and satiety. In non-obese individuals food ingestion is limited in part by this mechanism. In obese individuals, satiation and satiety are defective and unable to limit energy intake and prevent excessive weight gain. Several gastric electrical stimulatory (GES) devices have been developed, tested in clinical trials and even approved for the treatment of obesity. The design and clinical utility of three devices (Transend®, Maestro® and DIAMOND®) that have been extensively studied are presented as well as that of a new device (abiliti®) which is in early development. The Transcend®, a low energy GES device, showed promising results in open label studies but failed to show a difference from placebo in decreasing weight in obese subjects. The results of the clinical trials in treating obese subjects with the Maestro®, a vagal nerve stimulator, were sufficient to gain approval for marketing the device. The DIAMOND®, a multi-electrode GES device, has been used to treat type 2 diabetes and an associated benefit is to reduce body weight and lower systolic blood pressure.

Chronic gastric electrical stimulation leads to weight loss via modulating multiple tissue neuropeptide Y, orexin, α-melanocyte-stimulating hormone and oxytocin in obese rats.

OBJECTIVES: Gastric electrical stimulation (GES) has great potential for the treatment of obesity. We investigated the impact of chronic GES on the alteration of adipose tissue and the regulation of neuropeptide Y (NPY), orexin (OX), α-melanocyte-stimulating hormone (α-MSH) and oxytocin (OXT), and their receptors in several tissues. MATERIAL AND METHODS: Most of the experiments included three groups of diet-induced obesity rats: (1) sham-GES (SGES); (2) GL-6mA (GES with 6 mA, 4 ms, 40 Hz, 2 s on, 3 s off at lesser curvature); and (3) SGES-PF (SGES rats receiving pair feeding to match the consumption of GL-6mA rats). Chronic GES was applied for 2 h every day for 4 weeks. During treatment with GES, food intake and body weight were monitored weekly. The alteration of epididymal fat weight, gastric emptying, and expression of peptides and their receptors in several tissues were determined. RESULTS: GL-6mA was more potent than SGES-PF in decreasing body weight gain, epididymal fat tissue weight, adipocyte size and gastric emptying. Chronic GES significantly altered NPY, OX, α-MSH and OXT and their receptors in the hypothalamus, adipose tissue and stomach. CONCLUSIONS: Chronic GES effectively leads to weight loss by reducing food intake, fat tissue weight and gastric emptying. NPY, α-MSH, orexin and OXT, and their receptors in the hypothalamus, adipose tissue and stomach appear to be involved in the anti-obesity effects of chronic GES.

Neurostimulation of the gastrointestinal tract: review of recent developments.

OBJECTIVE: Neurostimulation is one manifestation of neuromodulation of the gastrointestinal (GI) tract. This manuscript reviews the history of neurostimulation of the GI tract with emphasis on current methods of stimulation. MATERIALS AND METHODS: A review was completed of the current research on GI neurostimulation methods with an emphasis on their clinical applications. RESULTS: Upper GI disorders can be modulated with both temporary (placed endoscopically or surgically) or permanent (placed surgically) gastric electrical stimulation (GES) devices. The current GI neurostimulation of stomach (GES) devices have been used in both children and adults, and some patients have been followed in excess of 15 years with good long-term results. Similar GES devices also have been used for a variety of lower GI disorders, including constipation and fecal incontinence, for a number of years. CONCLUSIONS: GI neurostimulation, as a type of neuromodulation, has been demonstrated to function at several locations in the GI tract for a variety of disorders. The future of neurostimulation in the GI tract will likely be influenced by a better understanding of pathophysiology as well as the development of new techniques and devices for neuromodulation.

The effects of individualized gastric electrical stimulation on food craving and gastrointestinal peptides in dogs.

BACKGROUND: Using an adjustable stimulator with a wide range of stimulation parameters, the aims of this study were 1) to investigate the effects of long-term gastric electrical stimulation (GES) on appetite and differential food cravings for three different foods and 2) to investigate the effects of GES on plasma gastrointestinal peptide concentrations. METHODS: The study was performed in eight Beagle dogs implanted with one pair of serosal electrodes. They were followed during GES and sham GES sessions in a crossover design. GES was conducted using a series of individualized parameters. Food intake and food cravings were observed to evaluate the effects of long-term GES. Enzyme-linked immunosorbent assay was used to measure the plasma concentrations of gastrointestinal peptides. RESULTS: Dogs on GES for three months ate significantly less food than those on sham GES for three months (p < 0.05). A significant change in food cravings was induced by GES. Dogs with GES ate significantly less high-fat food. However, there was no significant difference in consumption of high-carbohydrate food or balanced food between the periods of GES and sham GES. The plasma concentrations of ghrelin, peptide YY3-36, and glucagon-like peptide 1 did not differ significantly between the periods of GES and sham GES. CONCLUSIONS: Food intake and food craving were changed significantly by adjustable GES. GES may be used for treating obesity by changing food preferences. Further clinical studies are necessary to highlight the effect of adjustable GES on eating behavior.

Evaluation and treatment of gastric stimulator failure in patients with gastroparesis.

OBJECTIVE: This study evaluates treatment of gastroparesis patients refractory to gastric electrical stimulation (GES) therapy with surgical replacement of the entire GES system. SUMMARY BACKGROUND DATA: Some patients who have symptomatic improvement with GES later develop recurrent symptoms. Some patients improve by simply altering pulse parameter settings. Others continue to have symptoms with maximized pulse parameters. For these patients, we have shown that surgical implantation of a new device and leads at a different gastric location will improve symptoms of gastroparesis. METHODS: This study evaluates 15 patients with recurrent symptoms after initial GES therapy who subsequently received a second GES system. Positive response to GES replacement therapy is evaluated by symptoms scores for vomiting, nausea, epigastric pain, early satiety, and bloating using a modified Likert score system, 0 to 4. RESULTS: Total symptom scores improved for 12 of 15 patients with GES replacement surgery. Total score for the replacement group decreased from 17.3 ± 1.6 to 13.6 ± 3.7 with a difference of 3.6 (P value = .017). This score is compared with that of the control group with a preoperative symptom score of 15.8 ± 3.6 and postoperative score of 12.3 ± 3.5 with a difference of 3.5 (P value = .011). The control group showed a 20.3% decrease in mean total symptoms score, whereas the study group showed a 22.5% decrease in mean with an absolute reduction of 2.2. CONCLUSION: Reimplantation of a GES at a new gastric location should be considered a viable option for patients who have initially failed GES therapy for gastroparesis.