Gastric Electrical Stimulation Device Research Articles

Clinical Outcomes of a Large, Prospective Series of Gastric Electrical Stimulation Patients Using a Multidisciplinary Protocol.

Gastric electrical stimulation (GES) is an intervention used in the treatment of medically refractory gastroparesis. There are few large series demonstrating efficacy over a long-term follow-up period. This study reports clinical outcomes for patients from a single institution up to 5 years. A prospective database of patients undergoing GES implantation for gastroparesis was collected and reviewed. Patients were selected according to a multi-disciplinary institutional protocol. Baseline characteristics, including age, sex, smoking history, etiology of gastroparesis, and duration of gastroparesis symptoms, were collected. Symptomatic response was evaluated utilizing Gastroparesis Cardinal Symptom Index (GCSI) surveys pre-operatively and at subsequent follow-up visits. Other clinical outcome variables include medication use, hospitalizations due to gastroparesis, and overall satisfaction with symptom relief. Patient outcomes regarding reoperation and explantation were also recorded. 157 patients underwent GES at our institution since 2012. GCSI scores were collected in all patients at baseline, in 141 patients at 1 year follow-up, and in 110 patients at 5 years follow-up. Symptom severity in all 9 gastroparesis symptoms evaluated by the GCSI, as well as the total GCSI score, was reduced significantly at 1 year post-operatively, and these results were sustained at 5-year follow-up. Use of prokinetic and antiemetic medications was reduced during the follow-up period. Hospitalizations due to gastroparesis symptoms were also reduced. GES devices were explanted in 5 patients, 12 patients required generator exchanges, and 7 patients required reoperation due to displaced/eroded device leads during the study period. Gastric electrical stimulation is associated with sustained symptomatic relief, reduced reliance on medications, and reduced hospitalizations in gastroparesis patients selected utilizing our institutional protocol.

An Interactive System for Visualizing and Interpreting Propagating Vagal Nerve Activity to Improve the Efficacy of Gastric Electrical Stimulation for Gastroparesis

Gastroparesis is a stomach condition that results in abnormal processing of food and delayed gastric emptying without a mechanical obstruction. Nausea and vomiting are the most common symptoms. When pharmaceutical treatments and dietary changes fail to relieve symptoms, a gastric electrical stimulation (GES) device is implanted and used to electrically stimulate the stomach wall. Although the exact mechanism is unknown, there is evidence that GES stimulates the vagus nerve, which is the primary nerve that the stomach uses to communicate sensory information to the brain. We hypothesize that GES relieves nausea and vomiting by stimulating the vagus nerve. Vagal nerve recordings were obtained in human subjects receiving GES for gastroparesis using a novel, noninvasive method, consisting of placing a multi-electrode array (MEA) on the skin surface overlying the left and right cervical vagus nerves. The array allows for visualization of propagating nerve activity that is tied to the electrical stimulus delivered by the GES device. Since nerve signals propagate at specific speeds, the MEA can be used to learn properties of the vagal nerve pathways that transmit information to the brain in response to GES (Fig. 1A). Cervical measurements can also be collected from the subjects to determine optimal placement of the MEA. Due to the complex nature of the data sets collected, it is necessary to simplify the interpretation of the data to ensure that the importance of the signals is understood by a broad audience. A graphical user interface was created as an interactive tool to visualize and interpret vagal nerve activity using the data collected from the MEA. The interface includes a color-coded outline of the cervical measurements obtained on an image of the neck and a description of each measurement in terms of its anatomical position (Fig. 2A). It features an interactive component that allows users to view each measurement individually by selecting the identifying letter representative of each measurement (Fig. 2B). Users can select a subject from a drop-down menu, which results in automatic placement of the MEA on the image using the cervical anatomy measurements specific to that subject. To visualize nerve activity, a colormap is implemented where brighter colors denote activity (Fig. 1B). The data collected and analyzed from the MEA is the 70 millisecond window after each stimulus is applied. To maximize visualization, the rate of the activity is reduced and allows users to control the playback speed of the data using a slider. We are determining the limitations of detecting vagal nerve activity through the skin surface, including body mass index and the parameters of the GES device. Visualizing and analyzing the data traveling across the electrodes may provide insight into the typical anatomical course of the vagus nerve. We aim to use this display of vagal nerve activity to decode and analyze its involvements in GES and the treatment of gastroparesis.

Minimally Invasive Gastric Electrical Stimulation Using a Newly Developed Wireless Gastrostimulator: A Pilot Animal Study.

Background/AimsGastric electrical stimulation (GES) is a feasible modality for the treatment of gastroparesis; however, the presently available device requires invasive surgical implantation for long-term stimulation and repeated surgical procedure after a period of time. This study is aimed at developing a wireless miniature GES device and testing its endoscopic insertion in animal models.MethodsEndoscopic gastric implantation of the GES device was performed on 5 healthy weaner pigs under general anesthesia. We created an endoscopic submucosal pocket and inserted the gastro-electrical stimulator. In vivo gastric slow waves were recorded and measured during electrical stimulation. A multi-channel recorder, called an electrogastrogram, was used to record the gastric myoelectrical activity in the study.ResultsThe gastric slow waves on the electrogastrogram were more consistent with GES on the gastric tissues compared to no stimulation. The frequency-to-amplitude ratio was also significantly altered after the electrical stimulation.ConclusionsGES is feasible with our minimally invasive wireless device. This technique has the potential to increase utilization of GES as a treatment alternative.

Importance of endoscopy during permanent gastric stimulator placement.

Gastric electrical stimulation (GES) is an accepted form of therapy for gastroparesis and is considered for compassionate therapy in patients with refractory nausea and vomiting.1 The U.S. Food and Drug Administration has approved GES for treatment of drug-refractory idiopathic gastroparesis and diabetic gastroparesis because it has been shown to improve nausea and reduce vomiting frequency. It has also been used off label for related conditions.2,3 We present a case highlighting the methods and importance of performing endoscopy intraoperatively during placement of the permanent GES device and discuss possible adverse events that may arise.

Gastric Electrical Stimulation Reduces Refractory Vomiting in a Randomized Crossover Trial

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. 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. 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. 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.

Implantable Electronic Stimulation Devices from Head to Sacrum: Imaging Features and Functions.

Electronic stimulation devices are implanted in various locations in the body to decrease pain, modulate nerve function, or stimulate various end organs. The authors describe these devices using a craniocaudal approach, first describing deep brain stimulation (DBS) devices and ending with sacral nerve stimulation (SNS) devices. The radiology-relevant background information for each device and its imaging appearance are also described. These devices have a common design theme and include the following components: (a) a pulse generator that houses the battery and control electronics, (b) an insulated lead or wire that conveys signals to the last component, which is (c) an electrode that contacts the end organ and senses and/or acts on the end organ. DBS electrodes are inserted into various deep gray nuclei, most commonly to treat the symptoms of movement disorders. Occipital, trigeminal, and spinal nerve stimulation devices are used as second-line therapy to control craniofacial or back pain. For cardiac devices, the authors describe two newer devices, the subcutaneous implantable cardioverter defibrillator and the leadless pacemaker, both of which avoid complications related to having leads threaded through the venous system. Diaphragmatic stimulation devices stimulate the phrenic nerve to restore diaphragmatic movement. Gastric electrical stimulation devices act on various parts of the stomach for the treatment of gastroparesis or obesity. Finally, SNS devices are used to modulate urinary and defecatory functions. Common complications diagnosed at imaging include infection, hematoma, lead migration, and lead breakage. Understanding the components, normal function, and normal imaging appearance of each device allows the radiologist to identify complications. ©RSNA, 2019.

Treatment of Patients with Obese Type 2 Diabetes with Tantalus-DIAMOND® Gastric Electrical Stimulation: Normal Triglycerides Predict Durable Effects for at Least 3 Years.

The objectives of the present work are to evaluate long-term benefit of nonexcitatory gastric electrical stimulation (GES) by the DIAMOND(®) device on glycemic control and body weight in patients with type 2 diabetes inadequately controlled with oral agents and to determine the magnitude of the modulating effects of fasting plasma triglyceride (FTG) levels on these effects of GES. Sixty one patients with type 2 diabetes [HbA1c > 7.0% (53 mmol/mol) to < 10.5% (91 mmol/mol)] were implanted with the DIAMOND(®) GES device and treated with meal-mediated antral electrical stimulation for up to 36 months. The effects of baseline HbA1c and FTG on glycemic control, body weight, and systolic blood pressure were measured. GES reduced mean HbA1c by 0.9% and body weight by 5.7%. The effects were greater in patients with normal fasting plasma triglycerides (NTG) as compared to those with hypertriglyceridemia. The mean decrease in HbA1c in patients with NTG averaged 1.1% and was durable over 3 years of follow-up. ANCOVA indicated that improvement in HbA1c was a function of both baseline FTG group (p = 0.02) and HbA1c (p = 0.001) and their interaction (p = 0.01). Marked weight loss (≥ 10%) was observed in a significant proportion of NTG patients by 12 months of treatment and persisted through the 3 years. GES improves glycemic control and reduces body weight by a triglyceride-dependent mechanism in patients with type 2 diabetes inadequately controlled on oral agents. It is postulated that this is through a gut-brain interaction that modulates effects on the liver and pancreatic islets.

Tu1210 Long Term Symptom Outcome After an Evidence Based Medicine Trial of Gastric Electrical Stimulation

Background: We previously published (GIE 2011; 74: 496-503) an evidence based medicine study (CTRN 00432835) designed to evaluate the capacity of a 72 hour course of temporary mucosal gastric electrical stimulation (GES) to reduce nausea and vomiting, as well as other symptoms associated with the syndrome of gastroparesis. Following this study, we examined the outcomes data available from our long term clinical care of patients enrolled in the original trial subsequently implanted with permanent GES devices. Methods: Of the 58 patients in the original cross-over trial, 38 were approved by insurers and returned for permanent GES. The mean patient age was 46 years, 78% were female, 68% white, with 30% diabetic and 70% non-diabetic status. Average follow-up time in our clinical records was 4.1 years, with a maximum follow-up of 5.5 years (61% returned for 6-month followup, 71% for 12-month follow-up, and 63% for follow-up between 2.2 and 5.5 years after permanent stimulator placement). We employed a linear mixed model (random intercept), empirical Bayes approach to use the full longitudinal outcome trajectories in estimating patient-specific average long-term symptom levels after permanent placement. We then examined relationships between patient-specific final results with temporary stimulation (ON phase) during the trial and patient-specific, average long-term symptom levels. Results: Positive relationships between short-term and long-term outcomes existed, with significant associations for the Nausea and Total Symptom Score measures. We noted that 76% of the patients had no vomiting (Final Temp GES vomiting score=0) after 72 hours of temp GES, which, though a positive result from the original trial, interferes with our ability to determine associations with long-term outcomes due to minimal variation in the predictor of Vomiting (x-axis). For each unit increase in final temporary GES symptom Nausea, long-term Nausea outcomes showed associated increases of 0.3 units, 95% CI (0.02, 0.32) p=0.030. TSS showed similar significant associations between short and long-term outcomes, with a positive association of 2.1 units, (0.1, 4.1) p=0.045 (Figure 1). Gastric emptying tests (GET) for the whole group of patients changed little with temporary stimulation but did improve with long term GES, although the results were not statistically significant (Table 1). Conclusion: Long term follow up of a temporary double masked trial of endoscopic GES shows good correlation with the original symptoms improvements. We conclude that a trial of temporary GES can predict long term permanent GES outcome in patients with the symptoms of gastroparesis. Gastric motility measures pre and post treatment with GES: (N=37)

Neurostimulation of the gastrointestinal tract: review of recent developments.

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. A review was completed of the current research on GI neurostimulation methods with an emphasis on their clinical applications. 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. 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.

Gastric electrical stimulation for treatment of clinically severe gastroparesis

BACKGROUND:Severe, drug-resistant gastroparesis is a debilitating condition. Several, but not all, patients can get significant relief from nausea and vomiting by gastric electrical stimulation (GES). A trial of temporary, endoscopically delivered GES may be of predictive value to select patients for laparoscopic-implantation of a permanent GES device.MATERIALS AND METHODS:We conducted a clinical audit of consecutive gastroparesis patients, who had been selected for GES, from May 2008 to January 2012. Delayed gastric emptying was diagnosed by scintigraphy of ≥50% global improvement in symptom-severity and well-being was a good response.RESULTS:There were 71 patients (51 women, 72%) with a median age of 42 years (range: 14-69). The aetiology of gastroparesis was idiopathic (43 patients, 61%), diabetes (15, 21%), or post-surgical (anti-reflux surgery, 6 patients; Roux-en-Y gastric bypass, 3; subtotal gastrectomy, 1; cardiomyotomy, 1; other gastric surgery, 2) (18%). At presentation, oral nutrition was supplemented by naso-jejunal tube feeding in 7 patients, surgical jejunostomy in 8, or parenterally in 1 (total 16 patients; 22%). Previous intervention included endoscopic injection of botulinum toxin (botox) into the pylorus in 16 patients (22%), pyloroplasty in 2, distal gastrectomy in 1, and gastrojejunostomy in 1. It was decided to directly proceed with permanent GES in 4 patients. Of the remaining, 51 patients have currently completed a trial of temporary stimulation and 39 (77%) had a good response and were selected for permanent GES, which has been completed in 35 patients. Outcome data are currently available for 31 patients (idiopathic, 21 patients; diabetes, 3; post-surgical, 7) with a median follow-up period of 10 months (1-28); 22 patients (71%) had a good response to permanent GES, these included 14 (68%) with idiopathic, 5 (71%) with post-surgical, and remaining 3 with diabetic gastroparesis.CONCLUSIONS:Overall, 71% of well-selected patients with intractable gastroparesis had good response to permanent GES at follow-up of up to 2 years.

Development of innovative techniques for the endoscopic implantation and securing of a novel, wireless, miniature gastrostimulator (with videos)

Gastric stimulation via high-frequency, low-energy pulses can provide an effective treatment for gastric dysmotility; however, the current commercially available device requires surgical implantation for long-term stimulation and is powered by a nonrechargeable battery. To test and describe endoscopic implantation techniques and testing of stimulation of a novel, wireless, batteryless, gastric electrical stimulation (GES) device. Endoscopic gastric implantation techniques were implemented, and in vivo gastric signals were recorded and measured in a non-survival swine model (n = 2; 50-kg animals). Five novel endoscopic gastric implantation techniques and stimulation of a novel, wireless, batteryless, GES device were tested on a non-survival swine model. Feasibility of 5 new endoscopic gastric implantation techniques of the novel, miniature, batteryless, wireless GES device while recording and measurement of in vivo gastric signals. All 5 of the novel endoscopic techniques permitted insertion and securing of the miniaturized gastrostimulator. By the help of these methods and miniaturization of the gastrostimulator, successful GES could be provided without any surgery. The metallic clip attachment was restricted to the mucosal surface, whereas the prototype tacks, prototype spring coils, percutaneous endoscopic gastrostomy wires/T-tag fasteners, and submucosal pocket endoscopic implantation methods attach the stimulator near transmurally or transmurally to the stomach. They allow more secure device attachment with optimal stimulation depth. Non-survival pig studies. These 5 techniques have the potential to augment the utility of GES as a treatment alternative, to provide an important prototype for other dysmotility treatment paradigms, and to yield insights for new technological interfaces between non-invasiveness and surgery.

Sa1953 Delayed Gastric Emptying-Response to Temporary and Permanent GES With Effect on Symptoms and Gastric Emptying

Introduction: Gastric electrical stimulation (GES) appears to have a beneficial effect in disorders of foregut dysfunction but the mechanisms are unknown. We have previously reported that different electrical energies may cause differing responses when measured during surgical implantation of GES devices. We now report on a large series of consecutive patients who were given different magnitudes of electrical stimulation intraoperatively. We aimed to investigate the types of response to better understand the mechanisms of GES. Patients: We intraoperatively evaluated 87 consecutive patients with drug-refractory gastroparesis (68 female, 19 male; aged 13-76 years, mean 43.4 years; 37 diabetic, 50 idiopathic etiologies) who had elected treatment by permanent GES. Methods: Four energy settings were studied sequentially by using previously standardized parameters: low (pulse width, 330 μs; amplitude, 5 mA; frequency, 14 Hz; cycle ON, 0.1 s; cycle OFF, 5.0 s), medium (pulse width of 330 μs; amplitude, 10 mA; frequency, 28 Hz; cycle ON: 1.0 s; cycle OFF, 4.0 s), and high (pulse width of 450 μs; amplitude, 20 mA; frequency, 55 Hz; cycle ON: 4.0 s; cycle OFF, 1.0 s) energy settings, along with a ‘super high' setting (pulse width of 450 μs: amplitude 20mA; frequency, 130 Hz; cycle ON: 4.0 s; cycle OFF, 1.0 s). Surgical incision exposed the stomach. One pair of leads (‘Lead 1') was attached to the gastric serosa at the cardia-body junction, another pair (‘Lead 2') attached to the serosa at the antrum, and an initial 10-minute EGG recording was obtained simultaneously from each pair (‘Baseline Lead 1'; ‘Baseline Lead 2'). The cardia-body leads were then connected to the stimulator and used to deliver current for the remainder of the study. EGG frequency and amplitude were recorded through the antral leads. Results: Overall, mean frequency did not show much change with incremental GES energy settings. However many patients showed changes at low setting and a few showed irregular frequency changes throughout study session.(figure1, 2). Baseline mean (25%Q, 75%) frequency was 3.97[3.74, 4.21]cpm which changed to 4.01 (3.75, 4.27)cpm with low energy stimulation (p=0.942). Conclusions: Intraoperative delivery of differing energies to the stomach reveals diverse patterns of response in patients with the symptoms of gastroparesis. For the majority of patients, the greatest change seemed to occur at the first energy level applied without much further change with the application of increasing energy. This finding creates the question of whether the effect is caused by the mere application of energy or the amount applied. Further analysis of this data may help us better understand the mechanism of the beneficial effect of GES.

Sa1952 The Analysis of Different Electrical Energies Applied Intraoperatively May Help Understand the Mechanisms of Gastric Electrical Stimulation in Gastroparesis

Introduction: Gastric electrical stimulation (GES) appears to have a beneficial effect in disorders of foregut dysfunction but the mechanisms are unknown. We have previously reported that different electrical energies may cause differing responses when measured during surgical implantation of GES devices. We now report on a large series of consecutive patients who were given different magnitudes of electrical stimulation intraoperatively. We aimed to investigate the types of response to better understand the mechanisms of GES. Patients: We intraoperatively evaluated 87 consecutive patients with drug-refractory gastroparesis (68 female, 19 male; aged 13-76 years, mean 43.4 years; 37 diabetic, 50 idiopathic etiologies) who had elected treatment by permanent GES. Methods: Four energy settings were studied sequentially by using previously standardized parameters: low (pulse width, 330 μs; amplitude, 5 mA; frequency, 14 Hz; cycle ON, 0.1 s; cycle OFF, 5.0 s), medium (pulse width of 330 μs; amplitude, 10 mA; frequency, 28 Hz; cycle ON: 1.0 s; cycle OFF, 4.0 s), and high (pulse width of 450 μs; amplitude, 20 mA; frequency, 55 Hz; cycle ON: 4.0 s; cycle OFF, 1.0 s) energy settings, along with a ‘super high' setting (pulse width of 450 μs: amplitude 20mA; frequency, 130 Hz; cycle ON: 4.0 s; cycle OFF, 1.0 s). Surgical incision exposed the stomach. One pair of leads (‘Lead 1') was attached to the gastric serosa at the cardia-body junction, another pair (‘Lead 2') attached to the serosa at the antrum, and an initial 10-minute EGG recording was obtained simultaneously from each pair (‘Baseline Lead 1'; ‘Baseline Lead 2'). The cardia-body leads were then connected to the stimulator and used to deliver current for the remainder of the study. EGG frequency and amplitude were recorded through the antral leads. Results: Overall, mean frequency did not show much change with incremental GES energy settings. However many patients showed changes at low setting and a few showed irregular frequency changes throughout study session.(figure1, 2). Baseline mean (25%Q, 75%) frequency was 3.97[3.74, 4.21]cpm which changed to 4.01 (3.75, 4.27)cpm with low energy stimulation (p=0.942). Conclusions: Intraoperative delivery of differing energies to the stomach reveals diverse patterns of response in patients with the symptoms of gastroparesis. For the majority of patients, the greatest change seemed to occur at the first energy level applied without much further change with the application of increasing energy. This finding creates the question of whether the effect is caused by the mere application of energy or the amount applied. Further analysis of this data may help us better understand the mechanism of the beneficial effect of GES.

Temporary gastric electrical stimulation for gastroparesis: endoscopic placement of electrodes (ENDOstim)

Studies have shown high-frequency, low-energy gastric electrical stimulation (GES) to be an effective management strategy for patients with medication refractory gastroparesis. However, placement of a permanent GES device requires surgery and has considerable cost considerations. More importantly, however, this mode of therapy may not be successful for all patients. Patients likely to benefit from such an invasive and expensive procedure could be selected on the basis of their response to temporary GES. Electrodes for the purpose of temporary GES usually are placed percutaneously or through a percutaneous endoscopic gastrostomy (PEG) tube (PEGStim). This study demonstrated an easier and less cumbersome placement of these electrodes endoscopically [1-3]. The current case involved a 32-year-old man with diabetic gastroparesis. The endoscopic methods and protocol were approved by the Institutional Review Board at the University of Mississippi, Jackson, Mississippi. Informed consent was obtained before the procedure. Standard upper endoscopy was performed initially. A temporary cardiac pacing lead (Model 6414-200; Medtronic, Minneapolis, MN, USA) was used as the electrode. The video demonstrates an innovative technique of endoscopic placement of electrodes for temporary GES. The external stimulation device used was the standard GES device (Enterra; Medtronic). Temporary GES produced a rapid and marked improvement in the patient's intractable symptoms, improvement in his health-related quality-of-life score, electrogastrography parameters, and gastric emptying. Although the temporary electrodes could have been removed easily by gentle traction in a counterclockwise direction, the patient desired that the electrodes be left in place until permanent electrode placement. For patients such as the man in the current case, who do not have a preexisting PEG tube, the authors demonstrated that endoscopic placement of electrodes is technically feasible. The reported patient likely will benefit from surgical placement of a permanent GES device. Thus, the authors propose ENDOStim as the preferred method for placement of electrodes for temporary GES.

Sp710 Temporary Gastric Electrical Stimulation for Gastroparesis: Endoscopic Placement of Electrodes (ENDOStim)

Sp710 Temporary Gastric Electrical Stimulation for Gastroparesis: Endoscopic Placement of Electrodes (ENDOStim)

Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis

Our goal was to investigate associations between the status of interstitial cells of Cajal (ICC) and electrogastrogram (EGG) parameters, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty-one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c-kit and scored for the presence of ICC based on criteria obtained from 10 controls. All patients underwent EGG recordings, a 4-h standardized scintigraphic gastric emptying study and symptom assessment prior to the surgery. Based on antral biopsy, 15 patients (36%) had almost no ICC (ICC- group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in the ICC- group displayed significantly less normal slow waves than in the ICC+ group both in the fasting and fed states. Tachygastria in the ICC- group was significantly more than in the ICC+ group both in the fasting (32 +/- 8%vs 11 +/- 2%) and fed states (27 +/- 9%vs 12 +/- 2%). There was no statistical difference in gastric emptying, symptom severity of gastroparesis, aetiology, age and gender between the two groups. Severely depleted ICC occurs in up to 36% of gastroparetic patients and significantly correlates with an abnormal EGG. Severely depleted ICC does not correlate with the severity of gastroparesis as assessed by gastric emptying or symptom status but did result in a poorer symptomatic response to GES. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.

Effects of electrical stimulation on isolated rodent gastric smooth muscle cells evaluated via a joint computational simulation and experimental approach

Gastric electrical stimulation (GES) involves the delivery of electrical impulses to the stomach for therapeutic purposes. New GES protocols are needed that are optimized for improved motility outcomes and energy efficiency. In this study, a biophysically based smooth muscle cell (SMC) model was modified on the basis of experimental data and employed in conjunction with experimental studies to define the effects of a large range of GES protocols on individual SMCs. For the validation studies, rat gastric SMCs were isolated and subjected to patch-clamp analysis during stimulation. Experimental results were in satisfactory agreement with simulation results. The results define the effects of a wide range of GES parameters (pulse width, amplitude, and pulse-train frequency) on isolated SMCs. The minimum pulse width required to invoke a supramechanical threshold response from SMCs (defined at -30 mV) was 65 ms (at 250-pA amplitude). The minimum amplitude required to invoke this threshold was 75 pA (at 1,000-ms pulse width). The amplitude of the invoked response beyond this threshold was proportional to the stimulation amplitude. A high-frequency train of stimuli (40 Hz; 10 ms, 150 pA) could invoke and maintain the SMC plateau phase while requiring 60% less power and accruing approximately 30% less intracellular Ca(2+) concentration during the plateau phase than a comparable single-pulse protocol could in a demonstrated example. Validated computational simulations are an effective strategy for efficiently identifying effective minimum-energy GES protocols, and pulse-train protocols may also help to reduce the power consumption of future GES devices.

High‐Frequency Gastric Electrical Stimulation for the Treatment of Gastroparesis: A Meta‐Analysis

High-frequency gastric electrical stimulation (GES) is a relatively new treatment for medically refractory gastroparesis. There have been a number of clinical studies based on the use of a high-frequency stimulator (Enterra, Medtronic, Minneapolis, MN). A meta-analysis was performed to evaluate evidence for improved clinical outcome with this device. A literature search of major medical databases was performed for the period January 1992 to August 2008. Clinical studies involving an implanted high-frequency GES device were included and reported a range of clinical outcomes. Studies of external, temporary, and/or low-frequency GES were excluded. Of 13 included studies, 12 lacked controls and only one was blinded and randomized. Following GES, patients reported improvements in total symptom severity score (3/13 studies, mean difference 6.52 [confidence interval--CI: 1.32, 11.73]; P = 0.01), vomiting severity score (4/13, 1.45 [CI: 0.99, 1.91]; P < 0.0001), nausea severity score (4/13, 1.69 [CI: 1.26, 2.12]; P < 0.0001), SF-36 physical composite score (4/13, 8.05 [CI: 5.01, 11.10]; P < 0.0001), SF-36 mental composite score (4/13, 8.16 [CI: 4.85, 11.47]; P < 0.0001), requirement for enteral or parenteral nutrition (8/13, OR 5.53 [CI: 2.75, 11.13]; P < 0.001), and 4-h gastric emptying (5/13, 12.7% [CI: 9.8, 15.6]; P < 0.0001). Weight gain did not reach significance (3/13, 3.68 kg [CI: -0.23, 7.58]; P = 0.07). The device removal or reimplantation rate was 8.3%. Results show substantial benefits for high-frequency GES in the treatment of gastroparesis. However, caution is necessary in interpreting the results, primarily because of the limitations of uncontrolled studies. Further controlled studies are required to confirm the clinical benefits of high-frequency GES.

A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant

A 31-year-old woman with an 11-year history of poorly controlled type 1 diabetes mellitus was admitted with severe vomiting and ketoacidosis. The patient had been admitted to hospital on 14 occasions in the past 3 years for diabetic ketoacidosis precipitated by intractable vomiting, and she had been diagnosed with gastroparesis 2 years previously. Assessment of the patient's response to standard treatments for diabetic gastroparesis. These approaches involved tight glycemic control that included subcutaneous insulin infusion via a pump, correction of electrolyte disturbances, use of standard antiemetic and promotility agents, somatostatin-analog treatment, intrapyloric injection of botulinum toxin, and insertion of a percutaneous jejunal feeding tube. Severe diabetic gastroparesis refractory to standard treatments. The neurokinin-receptor antagonist aprepitant was started and her vomiting stopped within 24 h. This treatment was successfully continued for 4 months until a gastric electrical stimulation device was inserted, which enabled aprepitant treatment to be withdrawn and the percutaneous jejunostomy feeding tube to be removed. This successful treatment led to a substantial improvement in the patient's quality of life and overall glycemic control.

T1029 Lack of Utility of Lactulose Breath Testing in the Irritable Bowel Syndrome (IBS)

Background & Aims: High-frequency gastric electrical stimulation (GES) is a relatively new treatment for medically-refractory gastroparesis. A commercial device is available (Enterra, Medtronic, Minneapolis), and a number of clinical studies have been published reporting the efficacy of this treatment. A systematic review and meta-analysis was performed to evaluate the evidence for improved clinical outcome. Methods: A literature search of major medical databases was performed for the period January 1992 to August 2008. Clinical studies involving an implanted high-frequency GES device were included and a range of clinical outcomes were evaluated. Studies of external, temporary and/or low frequency GES were excluded. Because of a paucity of controlled trials, non-controlled clinical trials were also included for analysis. Results: Of the 26 studies located, 13 were accepted for inclusion. Of these studies, 12 lacked controls and only one was blinded and randomized. Following GES, patients reported improvements in total symptom severity score (3/13 studies, mean difference 6.52 [CI: 1.32, 11.73], p=0.01), vomiting severity score (4/13, 1.45 [CI: 0.99, 1.91], p<0.0001), nausea severity score (4/13, 1.69 [CI: 1.26, 2.12], p<0.0001), SF-36 physical composite score (4/13, 8.05 [CI: 5.01, 11.10], p<0.0001), SF-36 mental composite score (4/13, 8.16 [CI: 4.85, 11.47], p<0.0001), requirement for enteral or parenteral nutrition (8/13, OR 5.53 [CI: 2.75, 11.13], p<0.001) and 4-hour gastric emptying (5/13, mean improvement 12.7% [CI: 9.8, 15.6], p<0.0001). Weight gain following stimulation did not reach significance (3/13, 3.68kg [CI: -0.23, 7.58], p=0.07). The device removal or reimplantation rate was 8.3%, primarily due to infection (3%) or problems occurring at the site of implantation (4.9%). Conclusions This systematic review, of the best available evidence, finds significant and clinically important benefits for high-frequency GES in the treatment ofmedically-refractory gastroparesis. However, caution is necessary in interpreting the results, primarily due to the limitations of uncontrolled studies. Further controlled studies are required to confirm the clinical benefits of high-frequency GES. Results here provide strong grounds for the further development and evaluation of high-frequency GES.