Updates on gastric electrical stimulation to treat obesity: Systematic review and future perspectives

AIM: To evaluate the current state-of-the-art of gastric electrical stimulation to treat obesity. METHODS: Systematic reviews of all studies have been conducted to evaluate the effect of different types of gastric electrical stimulation(GES) on obesity.RESULTS: Thirty-one studies consisting of a total of 33 different trials were included in the systematic review for data analysis. Weight loss was achieved in most studies, especially during the first 12 mo, but only very few studies had a follow-up period longer than 1 year. Among those that had a longer follow-up period, many were from the Transcend(Implantable Gastric Stimulation) device group and maintained significant weight loss. Other significant results included changes in appetite/satiety, gastric emptying rate, blood pressure and neurohormone levels or biochemical markers such as ghrelin or HbA1 c respectively. CONCLUSION: GES holds great promises to be an effective obesity treatment. However, stronger evidence is required through more studies with a standardized way of carrying out trials and reporting outcomes, to determine the long-term effect of GES on obesity.

Long-pulse gastric electrical stimulation protects interstitial cells of Cajal in diabetic rats via IGF-1 signaling pathway

AIM: To investigate the effects of different parameters of gastric electrical stimulation (GES) on interstitial cells of Cajal (ICCs) and changes in the insulin-like growth factor 1 (IGF-1) signal pathway in streptozotocin-induced diabetic rats. METHODS: Male rats were randomized into control, diabetic (DM), diabetic with sham GES (DM + SGES), diabetic with GES1 (5.5 cpm, 100 ms, 4 mA) (DM + GES1), diabetic with GES2 (5.5 cpm, 300 ms, 4 mA) (DM + GES2) and diabetic with GES3 (5.5 cpm, 550 ms, 2 mA) (DM + GES3) groups. The expression levels of c-kit, M-SCF and IGF-1 receptors were evaluated in the gastric antrum using Western blot analysis. The distribution of ICCs was observed using immunolabeling for c-kit, while smooth muscle cells and IGF-1 receptors were identified using alpha-SMA and IGF-1R antibodies. Serum level of IGF-1 was tested using enzyme-linked immunosorbent assay. RESULTS: Gastric emptying was delayed in the DM group but improved in all GES groups, especially in the GES2 group. The expression levels of c-kit, M-SCF and IGF-1R were decreased in the DM group but increased in all GES groups. More ICCs (c-kit(+)) and smooth muscle cells (alpha-SMA(+)/IGF-1R(+)) were observed in all GES groups than in the DM group. The average level of IGF-1 in the DM group was markedly decreased, but it was up-regulated in all GES groups, especially in the GES2 group. CONCLUSION: The results suggest that long-pulse GES promotes the regeneration of ICCs. The IGF-1 signaling pathway might be involved in the mechanism underlying this process, which results in improved gastric emptying.

Gastric electrical stimulation for gastroparesis:A goal greatly pursued,but not yet attained

The lack of an effective medical treatment for gastroparesis has pushed the research of new techniques of gastric electrical stimulation (GES) for nearly half a century of experimentation with a large variety of electrical stimuli delivered to the gastric wall of animals and patients with gastroparesis. Three principal methods are currently available: gastric low-frequency/high-energy GES with long pulse stimulation, high-frequency/low-energy GES with short pulse stimulation and neural sequential GES. The first method aims to reset a regular slow wave rhythm, but has variable effects on contractions and requires devices with large and heavy batteries unsuitable for implantation. High-frequency/low-energy GES, although inadequate to restore a normal gastric electro-mechanical activity, improves dyspeptic symptoms, such as nausea and vomiting, giving patients a better quality of life together with a more satisfactory nutritional status and is suitable for implantation. Unfortunately, the numerous clinical studies using this type of GES, with the exception of two, were not controlled and there is a need for definitive verification of the effectiveness of this technique to justify the cost and the risks of this procedure. The last method, which is neural sequential GES, consists of a microprocessor-controlled sequential activation of a series of annular electrodes along the distal two thirds of the stomach and is able to induce propagated contractions causing forceful emptying of the gastric content. The latter method is the most promising, but has been used only in animals and needs to be tested in patients with gastroparesis before it is regarded as a solution for this disease.

Effect of two-channel gastric electrical stimulation with trains of pulses on gastric motility

AIM： To investigate the effect of two-channel gastric electrical stimulation （GES） with trains of pulses on gastric emptying and slow waves.METHODS： Seven dogs implanted with four pairs of electrodes and equipped with a duodenal cannula were involved in this study. Two experiments were performed.The first experiment included a series of sessions in the fasting state with trains of short or long pulses, each lasted 10 min. A 5-min recording without pacing was made between two sessions. The second experiment was performed in three sessions （control, single-channel GES, and two-channel GES）. The stimulus was applied via the 1st pair of electrodes for single-channel GES （GES via one pair of electrodes located at 14 cm above the pylorus）, and simultaneously via the 1st and 3rd channels for two-channel GES （GES via two pairs of electrodes located at 6 and 14 cm above the pylorus）, Gastric liquid emptying was collected every 15 min via the cannula for 90 min.RESULTS： GES with trains of pulses at a pulse width of 4 ms or higher was able to entrain gastric slow waves. Two-channel GES was about 50% more efficient than single-channel GES in entraining gastric slow waves. Two-channel but not single-channel GES with trains of pulses was capable of accelerating gastric emptying in healthy dogs. Compared with the control session, two-channel GES significantly increased gastric emptying of liquids at 15 rain （79.0% ± 6.4% vs 61.3% ± 6.1%, P 〈 0.01）, 30 min （83.2% ± 6.3 % vs 68.2% ± 6.9%, P 〈 0.01）, 60 min （86.9% ± 5.5 % vs 74.1% ± 5.9%, P 〈 0.01）, and 90 rain （91.0% ± 3.4% vs 76.5% ± 5.9%, P 〈 0.01）.CONCLUSION： Two-channel GES with trains of pulses accelerates gastric emptying in healthy dogs and may have a therapeutic potential for the treatment of gastric motility disorders.

Visceral response to acute retrograde gastric electrical stimulation in healthy human

AIM: To investigate the visceral response to acute retrograde gastric electrical stimulation (RGES) in healthy humans and to derive optimal parameters for treatment of patients with obesity.METHODS: RGES with a series of effective parameters were performed via a bipolar mucosal electrode implanted along the great curvature 5 cm above pylorus of stomach in 12 healthy human subjects. Symptoms associated with dyspepsia and other discomfort were observed and graded during RGES at different settings, including long pulse and pulse train. Gastric myoelectrical activity at baseline and during different settings of stimulation was recorded by a multi-channel electrogastrography.RESULTS: The gastric slow wave was entrained in all the subjects at the pacing parameter of 9 cpm in frequency, 500 ms in pulse width, and 5 mA in amplitude.The frequently appeared symptoms during stimulation were satiety, bloating, discomfort, pain, sting, and nausea. The total symptom score for each subject significantly increased as the amplitude or pulse width was adjusted to a higher scale in both long pulse and pulse train. There was a wide diversity of visceral responses to RGES among individuals.CONCLUSION: Acute RGES can result in a series of symptoms associated with dyspepsia, which is beneficial to the treatment of obesity. Optimal parameter should be determined according to the individual sensitivity to electrical stimulation.

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.

Central Opioid Peptide-containing Neurons Mediates Therapeutic Effect of Short-pulse Gastric Electrical Stimulation on Dyspepsia-like Symptoms in Dogs

This study investigated whether the curative effect of short-pulse gastric electrical stimulation （GES） on the vasopressin-induced dyspeptic symptoms was mediated by central opioid peptide-producing neurons. Five female beagle dogs implanted with 1 pair of electrodes in gastric serosa were used in a two-experiment study. In experiment one, the brain was scanned by positron emission tomography in 3 dogs with and without short-pulse GES, and the radioactivity in nuclei of solitary tract （NST） and hypothalamus was detected. Experiment two was composed of 4 sessions. In session one, the dogs were injected with vasopressin in the absence of short-pulse GES. With session two, the short-pulse GES was simultaneously given via the electrodes with the injection of vasopressin. In sessions three and four, naloxone and naloxone methiodide was administered respectively in the presence of short-pulse GES. Motion sickness-like symptoms were scored and compared among the different sessions. The results showed that the short-pulse GES significantly increased the radioactivity in NST and hypothalamic nuclei （P〈0.05, vs control）. The short-pulse GES could ameliorate the vasopressin-induced motion sickness-like symptoms in dogs. Naloxone, but not naloxone methiodide could attenuate the curative effects of short-pulse GES. It is concluded that NST and hypothalamic nuclei may participate in the mediation of the curative effects of short-pulse GES on dyspepsia-like symptoms. Central opioid peptide-containing neurons presumably mediate the therapeutic effect on dyspeptic symptoms of short-pulse GES.

Electrogastrogram Recovery for Correction of Gastric Disorders Using Gastric Stimulator

Gastric disorders play an important role in digestive system of a human subject. Gastric disorder is due to the gastric dysmotility due to delayed gastric emptying and other motor dysfunctions like impaired fundic distention. Nowadays invasive technique like laparoscopy procedure, endoscopy procedure and surgery procedure plays a vital role in investigation of gastric disorders. Electrogastrogram is a noninvasive technique for analyzing digestive system disorders. In this proposed work, stimulation is delivered with the electrode package with camera, which travels through an esophagus to reach stomach and stimulate the interstitial cajal cells. Due to this stimulation the stomach starts, its activity a potential is provided that is recorded with electrode setup, which is called electrogastrogram. It is verified with its normal range 3 cpm. The stimulation includes pulses mode and continuous mode. Stomach function is recovered and its frequency is measured and the same is compared with normal range value. Depending upon the subject condition, the gastric activity is improved by setting different values of duty cycle. By this procedure the subject avoid painful procedure, stay in hospital, frequently and the cost is minimum.

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.

Treatment of refractory diabetic gastroparesis: Western medicine and traditional Chinese medicine therapies

Refractory diabetic gastroparesis(DGP),a disorder that occurs in both type 1 and type 2 diabetics,is associated with severe symptoms,such as nausea and vomiting,and results in an economic burden on the health care system.In this article,the basic characteristics of refractory DGP are reviewed,followed by a discussion of therapeutic modalities,which encompasses the definitions and clinical manifestations,pathogenesis,diagnosis,and therapeutic efficacy evaluation of refractory DGP.The diagnostic standards assumed in this study are those set forth in the published literature due to the absence of recognized diagnosis criteria that have been assessed by an international organization.The therapeutic modalities for refractory DGP are as follows:drug therapy,nutritional support,gastricelectrical stimulation,pyloric botulinum toxin injection,endoscopic or surgical therapy,and traditional Chinese treatment.The therapeutic modalities may be used alone or in combination.The use of traditional Chinese treatments is prevalent in China.The effectiveness of these therapies appears to be supported by preliminary evidence and clinical experience,although the mechanisms that underlie these effects will require further research.The purpose of this article is to explore the potential of combined Western and traditional Chinese medicine treatment methods for improved patient outcomes in refractory DGP.

Fluoroscopic gastric peroral endoscopic pyloromyotomy(G-POEM)in patients with a failed gastric electrical stimulator

Background:Gastric electrical stimulators(GESs)have been used to treat refractory gastroparesis in patients who fail initial therapies such as dietary modifications,control of psychological stressors and pharmacologic treatment.More recently,gastric peroral endoscopic pyloromyotomy(G-POEM)has emerged as a novel endoscopic technique to treat refractory gastroparesis.We present a case series of patients with refractory gastroparesis who failed treatment with an implanted GES that were safely treated with G-POEM performed under fluoroscopy as a salvage therapy.Methods:Cases of G-POEM performed on patients with refractory gastroparesis who failed treatment with a GES were retrospectively reviewed.All G-POEM procedures were performed under fluoroscopic guidance with the GES still in place.Gastroparesis Cardinal Symptoms Index(GCSI)and gastric emptying scintigraphy were assessed before and after the procedure.Patients were followed up for up to 18 months post procedure.Results:Five patients underwent G-POEM after failing treatment with a GES.Under fluoroscopy,the GES and their leads were visualized in different parts of the stomach.One GES lead was observed at the antrum near the myotomy site.All procedures were successfully completed without complications.Patients’GCSI decreased by an average of 62%1 month post procedure.Patients also had notable improvements in gastric emptying 2 months post procedure.Conclusion:In patients with refractory gastroparesis who have failed treatment with a GES,G-POEM can be safe and effective without removing the GES.To visualize the GES and avoid cutting GES leads during myotomy,the procedure should be performed under fluoroscopy.