Zhiyue Lin

Gastric pacing improves emptying and symptoms in patients with gastroparesis.

BACKGROUND & AIMS No effective treatment is available for patients with gastroparesis refractory to standard medical therapy. The aim of this study was to investigate the effects of gastric pacing on gastric electrical activity, gastric emptying, and symptoms in patients with gastroparesis. METHODS Nine patients with gastroparesis participated in this study. Four pairs of cardiac pacing wires were implanted on the serosa of the stomach. The protocol consisted of two portions: a temporary inpatient study period and an outpatient study for a period of 1 month or more. RESULTS Gastric pacing entrained the gastric slow wave in all subjects and converted tachygastria in 2 patients into regular 3-cpm slow waves. Gastric emptying was significantly improved after the outpatient treatment with gastric pacing. The gastric retention at 2 hours was reduced from 77.0% +/- 3.3% to 56.6% +/- 8.6% (P < 0.05). Symptoms of gastroparesis were substantially reduced at the end of the outpatient treatment (1.51 +/- 0.46 vs. 2.84 +/- 0.61; P < 0.04). Eight of 9 patients no longer relied on jejunostomy tube feeding, and no adverse events were noted related to the pacing unit. CONCLUSIONS Gastric pacing seems to be able to improve symptoms of gastroparesis and to accelerate gastric emptying in patients with gastroparesis. More controlled studies are necessary to further investigate the role of gastric pacing in clinical practice.

Absence of the interstitial cells of Cajal in patients with gastroparesis and correlation with clinical findings

The interstitial cells of Cajal (ICCs) are fundamental in the generation of gastric slow waves. The role of these cells in gastroparesis has not been established. We studied 14 gastroparetic patients (9 diabetic, 4 idiopathic, and 1 postsurgical) for whom standard medical therapy had failed and who had been treated with a gastric electrical stimulator for at least 3 months. All patients had a full-thickness antral gastric wall biopsy at the time of surgery. The biopsy samples were stained with c -kit and scored for the presence of ICCs. Baseline electrogastrogram recordings were obtained for 30 minutes in the fasting state and for 2 hours after a test meal. The patients assessed their total symptom score at baseline and at 3 months. Five patients had almost no ICCs and were compared with nine patients with 20% to normal cell numbers. Both groups did respond symptomatically to gastric electrical stimulation. However, patients with depleted ICCs had significantly more tachygastria and had significantly greater total symptom scores at baseline and after 3 months of gastric electrical stimulation. ICCs are absent in some patients (up to a third) with diabetic or idiopathic gastroparesis, and the absence of these cells is associated with abnormalities of gastric slow waves, worse symptoms, and less improvement with gastric electrical stimulation.

Artifact reduction in electrogastrogram based on empirical mode decomposition method

Severe contamination of the gastric signal in electrogastrogram (EGG) analysus by respiratory, motion, cardiac artifacts, and possible myoelectrical activity from other organs, poses a major challenge to EGG interpretation and analysis. A generally applicable method for removing a variety of artifacts from EGG recordings is proposed based on the empirical mode decomposition (EMD) method. This decomposition technique is adaptive, and appears to be uniquely suitable for nonlinear, non-stationary data analysis. The results show that this method, combined with instantaneous frequency analysis, effectively separate, identify and remove contamination from a wide variety of artifactual sources in EGG recordings.

Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis.

Abstract  The aims were to determine symptom responses and long‐term outcomes in gastroparetic patients receiving gastric electrical stimulation (GES) therapy beyond 3 years by presenting per protocol analysis and intention‐to‐treat (ITT) analysis. Data collected at baseline, 1 year and beyond 3 years in 55 patients included total symptom scores (TSS), nutritional status, weight, hospitalizations, the use of prokinetic and/or antiemetic medications, HbA1c in diabetics and adverse events. Of the 55 patients, 10 died of non‐pacemaker‐related complications, six had the devices removed and two could not be reached. The remaining 37 patients had the device activated for a mean of 45 months. Both per protocol and ITT analysis demonstrated that TSS, hospitalization days and the use of medications were all significantly reduced at 1 year and were sustained beyond 3 years. Average TSS decreased by 62.5% for the 37 patients completing 3 years of GES. At implantation, 15/37 patients required nutritional support and only five continued beyond 3 years. Mean HbA1c level in diabetics was significantly reduced from 9.5 to 7.9% at 3 years. We conclude that a significant improvement in symptoms and all measures of clinical outcome can be maintained for greater than 3 years with GES in patients with refractory gastroparesis.

Chronic gastric electrical stimulation for gastroparesis reduces the use of prokinetic and/or antiemetic medications and the need for hospitalizations.

To investigate the effect of chronic gastric electrical stimulation (GES) on the daily use of prokinetics and antiemetics, hospitalizations, total symptom score (TSS), SF-36 status for health-related quality of life (HQOL), and gastric emptying of a solid meal, we evaluated 37 gastroparetic patients preoperatively and 1 year after undergoing GES implant. Prokinetic and antiemetic use was significantly reduced. Of 27 patients on at least one prokinetic at baseline, 8 were off at 1 year. Twenty-six patients requiring antiemetics before surgery decreased to 17. Mean TSS was significantly reduced and the reduction for patients off medications was significantly better than for patients still on medications. Overall SF-36 scores for HQOL were significantly improved, and patients off antiemetics had a significantly higher HQOL score than for patients on antiemetics at 1 year. Hospitalizations decreased from 50 ± 10 days for the year prior to GES therapy to 14± 3 days (P < 0.05). However, gastric emptying was not significantly improved. Conclusions are as follows. (1) Chronic GES significantly reduced the use of prokinetic/antiemetic medications and the need for hospitalization in gastropraretic patients, whose clinical and quality of life outcomes also significantly improved (2) These data provide evidence of the positive economic impact of this new therapy on long-term clinical outcomes in gastroparetic patients not responding to standard medical therapy.

Clinical response to gastric electrical stimulation in patients with postsurgical gastroparesis

BACKGROUND & AIMS The aim of this study was to report the long-term clinical response to high-frequency gastric electrical stimulation (GES) in 16 patients with postsurgical gastroparesis who failed standard medical therapy. METHODS Clinical data collected at baseline and after 6 and 12 months of GES included (1) severity and frequency of 6 upper gastrointestinal (GI) symptoms by using a 5-point symptom interview questionnaire and total symptom score, (2) health-related quality of life including physical composite score and mental composite score, (3) 4-hour standardized gastric emptying of a solid meal by scintigraphy, and (4) nutritional status. RESULTS The severity and frequency of all 6 upper GI symptoms, total symptom score, physical composite score, and mental composite score were significantly improved after 6 months and sustained at 12 months ( P < .05). All patients had delayed gastric emptying at baseline. Gastric emptying was not significantly faster at 12 months, although 3 normalized. At implantation, 7 of 16 patients required nutritional support with a feeding jejunostomy tube; after GES, 4 were able to discontinue jejunal feeding. The mean number of hospitalization days was significantly reduced by a mean 25 days compared with the prior year. One patient had the device removed after 12 months because of infection around the pulse generator. CONCLUSIONS Long-term GES significantly improved upper GI symptoms, quality of life, the nutritional status, and hospitalization requirements of patients with postsurgical gastroparesis. Although vagal nerve damage or disruption was part of the underlying pathophysiology, GES therapy was still effective and is a potential treatment option for the long-term management of postsurgical gastroparesis. A controlled clinical trial of GES for PSG patients (who are refractory to medical therapy) is indicated given these encouraging results.

Gastric Electrical Stimulation Improves Outcomes of Patients With Gastroparesis for up to 10 Years

BACKGROUND & AIMS We assessed the long-term clinical outcomes of gastric electrical stimulation (GES) therapy with Enterra (Enterra Therapy System; Medtronic, Minneapolis, MN) in a large cohort of patients with severe gastroparesis. METHODS Gastroparesis patients (n=221; 142 diabetic, 48 idiopathic, and 31 postsurgical) treated with Enterra (Medtronic) for 1-11 years were retrospectively assessed; 188 had follow-up visits and data were collected for at least 1 year (mean 56 months, range 12-131 months). Total symptom scores (TSSs), gastric emptying, nutritional status, weight, hospitalizations, use of prokinetic and/or antiemetic medications, levels of HbA1c levels (in diabetic patients), and adverse events were evaluated at the beginning of the study (baseline) and during the follow-up period. RESULTS TSS, hospitalization days, and use of medications were significantly reduced among all patients (P<.05). More patients with diabetic (58%) and postsurgical gastroparesis (53%) had a greater than 50% reduction in TSS than those with idiopathic disease (48%; P=.32). Weight significantly increased among all groups, and 89% of J-tubes could be removed. At end of the follow-up period, all etiological groups had similar, abnormal delays in mean gastric retention. Thirteen patients (7%) had their devices removed because of infection at the pulse generator site. CONCLUSIONS GES therapy significantly improved subjective and objective parameters in patients with severe gastroparesis; efficacy was sustained for up to 10 years and was accompanied by good safety and tolerance profiles. Patients with diabetic or postsurgical gastroparesis benefited more than those with idiopathic disease.

Effect of high‐frequency gastric electrical stimulation on gastric myoelectric activity in gastroparetic patients

Abstract  The aim of this study was to investigate the effect of gastric electrical stimulation (GES) on gastric myoelectric activity (GMA) and to identify possible mechanisms that could help explain how high‐frequency GES is effective in treating nausea and vomiting associated with gastroparesis. Fifteen gastroparetic patients who received high‐frequency GES were enrolled. Two pairs of temporary pacing wires were implanted on the serosa of the stomach along the greater curvature during surgery for placement of the permanent stimulation device. Two‐channel serosal recordings of GMA before and during GES were measured. A gastric emptying test and severity of nausea and vomiting were assessed at baseline and at 3 months of GES. Power spectral and cross correlation analyses revealed that impaired propagation of slow waves (50%), tachygastria (30%) and abnormal myoelectric responses to a meal (50%) were the main abnormalities observed at baseline. GES with a high frequency significantly enhanced the slow wave amplitude and propagation velocity, and resulted in a significant improvement in nausea and vomiting but did not entrain the gastric slow wave or improve gastric emptying after 3 months of GES.

Clinical, psychiatric and manometric profile of cyclic vomiting syndrome in adults and response to tricyclic therapy

Abstract  Our goal was to investigate 31 adult patients (mean age 29 years, range 18–62 years) meeting Rome II criteria for cyclic vomiting syndrome (CVS). All subjects completed a clinical questionnaire, a Hamilton Rating Scale for Anxiety (HAM‐A) and Zung Depression Inventory. Gastric emptying time was assessed in 30 subjects and electrogastrogram (EGG) in 11 between acute attacks. Twenty‐seven patients treated with amitriptyline completed a follow‐up questionnaire. The mean age of onset of the patients was 30 years (range 14–53 years) and cycles of nausea and vomiting were accompanied by often‐severe epigastric and diffuse abdominal pain. A typical attack ranged from 1 to 14 days, with the majority being 4–6 days. The HAM‐A revealed that 84% had an anxiety disorder, and based on Zung Depression Inventory 78% suffered from mild‐to‐severe depression. Only 4 (13%) patients reported migraine, but 14 had a family history of migraine. Gastric emptying time was rapid in 23 (77%), normal in 4 and delayed in 3. The EGG was abnormal in 7 of 11 patients, with 4 having tachygastria. Of 13 patients using marijuana, 7 had symptom relief, while 2 had resolution of CVS after stopping use. The overall treatment experience in the 24 patients receiving amitriptyline up to 1 mg kg−1 day−1 for at least 3 months indicated that 93% had decreased symptoms and 26% achieved full remission. Cyclic vomiting syndrome in adults has the following hallmarks: prominence of accompanying abdominal pain and increased prevalence of anxiety and depression, rapid gastric emptying and tachygastric EGG, and successful suppression of attacks by chronic amitriptyline therapy.

Mechanisms of symptomatic improvement after gastric electrical stimulation in gastroparetic patients

Abstract  The aims were to investigate the effects of gastric electrical stimulation (GES) on autonomic function, gastric distention and tone, and central control mechanisms in gastroparetic patients. Ten gastroparetic patients refractory to standard medical therapy participated in this study and data were collected at baseline, within two weeks before surgery for implantation of GES system, and at follow‐up sessions between 6 and 12 weeks after GES therapy was initiated. In each session, electrocardiogram, electrogastrogram (EGG) and gastric barostat measurements were conducted before and after a caloric liquid meal. Positron Emission Tomography (PET) brain scans were performed on a separate day. During GES therapy there was a significant increase in the discomfort threshold for mean pressure from 21 mmHg at baseline to 25 mmHg at follow‐up, and for mean volume from 561 mL to 713 mL. A significant increase in the postprandial EGG power (amplitude) was observed between baseline and follow up. The sympathovagal balance was significantly decreased after GES therapy, indicating a significant increase in vagal activity. The cumulative PET data showed an increase in quantitative radioactive counts relative to the standardized data base in both the thalamic and caudate nuclei after chronic GES therapy. We conclude that our data suggest that the symptomatic improvement achieved by GES in gastroparesis is best explained by activation of vagal afferent pathways to influence CNS control mechanisms for nausea and vomiting accompanied by enhanced vagal efferent autonomic function and decreased gastric sensitivity to volume distention which enhances postprandial gastric accommodation.