Irene Sarosiek

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.

Gastric myoelectrical activity and gastric emptying in patients with functional dyspepsia

OBJECTIVES:The aims of this study were to investigate gastric myoelectrical activity and gastric emptying (GE) and their relationship in patients with functional dyspepsia.METHODS:The study was conducted in 15 healthy volunteers (six women, nine men, mean age: 42 yr) and 15 patients (13 women, two men, mean age: 43 yr) with functional dyspepsia. Gastric myoelectrical activity was recorded using cutaneous electrogastrography (EGG) for 30 min in the fasting state and for 120 min simultaneously with GE monitoring after an isotope-labeled solid meal. The anterior/posterior images of the stomach were taken using a technetium scanner immediately after eating, and then at 1, 2, and 4 h to determine the percentage of gastric retention. The dominant frequency of the EGG, the change of the postprandial EGG peak power (δP), and the percentage of normal 2–4 cycles/min (cpm) slow waves during each recording session were calculated and compared between the patients and healthy subjects.RESULTS:The patients had a significantly lower mean percentage of 2–4 cpm slow waves, both in the fed state and in the fasting state, than did healthy subjects. Compared to the EGG in the fasting state, a significant increase of the EGG dominant frequency in the fed state was observed in healthy subjects but not in the patients. The mean postprandial EGG power increase in the patients was substantially less than in the healthy subjects during the first postprandial hour but similar during the second postprandial hour. The mean percentage of gastric retention in patients is substantially higher than in the healthy subjects, both at 2 h after eating and at 4 h after eating. Of 15 patients, nine (60%) had delayed GE (gastric retention at 2 h >50%) and 10 (66%) had abnormal EGGs (percentage of 2–4 cpm <70% and/or δP < 0). Eight of these 10 patients (80%) with abnormal EGGs had delayed GE.CONCLUSIONS:A high proportion of adult patients (60%) with functional dyspepsia have abnormally slow GE and abnormalities in gastric myoelectrical activity.

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

Abstractu2002 The aims were to determine symptom responses and long‐term outcomes in gastroparetic patients receiving gastric electrical stimulation (GES) therapy beyond 3u2003years by presenting per protocol analysis and intention‐to‐treat (ITT) analysis. Data collected at baseline, 1u2003year and beyond 3u2003years 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 45u2003months. Both per protocol and ITT analysis demonstrated that TSS, hospitalization days and the use of medications were all significantly reduced at 1u2003year and were sustained beyond 3u2003years. Average TSS decreased by 62.5% for the 37 patients completing 3u2003years of GES. At implantation, 15/37 patients required nutritional support and only five continued beyond 3u2003years. Mean HbA1c level in diabetics was significantly reduced from 9.5 to 7.9% at 3u2003years. We conclude that a significant improvement in symptoms and all measures of clinical outcome can be maintained for greater than 3u2003years 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 & AIMSnThe 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.nnnMETHODSnClinical 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnLong-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.

The assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology

Backgroundu2002 Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times.

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

BACKGROUND & AIMSnWe 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.nnnMETHODSnGastroparesis 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.nnnRESULTSnTSS, 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.nnnCONCLUSIONSnGES 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

Abstractu2002 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 3u2003months 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 3u2003months of GES.

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

Abstractu2002 Our goal was to investigate 31 adult patients (mean age 29u2003years, range 18–62u2003years) 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 30u2003years (range 14–53u2003years) and cycles of nausea and vomiting were accompanied by often‐severe epigastric and diffuse abdominal pain. A typical attack ranged from 1 to 14u2003days, with the majority being 4–6u2003days. 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 1u2003mgu2003kg−1u2003day−1 for at least 3u2003months 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.

Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study

Backgroundu2002 Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP‐101, is in clinical development for treatment of gastroparesis. This double‐blind, randomized, placebo‐controlled study evaluated the safety and efficacy of multiple TZP‐101 doses in patients with moderate to severe symptomatic diabetic gastroparesis.