Tl Abell

Is gastric electrical stimulation superior to standard pharmacologic therapy in improving GI symptoms, healthcare resources, and long-term health care benefits?

Abstract  Context:  Severe upper gastrointestinal (GI) motor disorders, including gastroparesis (GP), can consume significant health care resources. Many patients are refractory to traditional drug therapy.

An energy algorithm improves symptoms in some patients with gastroparesis and treated with gastric electrical stimulation

Abstract  Gastric electrical stimulation (GES) is effective to improve symptoms of nausea and vomiting in most patients, but very little is known about the effect of varying stimulation parameters. We analysed stimulation parameters in a pilot study of 22 patients (12 idiopathic, four diabetic and four postsurgical) with drug‐refractory gastroparesis who did not respond optimally to initial settings. Patients underwent high‐frequency/lowenergy GES using identical initial stimulation parameters: 5 mA of current, 330 μs pulse width, 14 Hz for 0.1 s on and 5.0 s off. Due to lack on optimal response, 22 patients underwent alteration of an algorithm using stimulation parameters. At follow‐up (mean of 4.3 years) a dose–response relationship for charge, power and energy were compared with baseline for the whole group and for each diagnostic subgroup by anovadata are reported as mean ± SE. Based on the mean of individual dose–response curves, differences in data are charge, current per pulse and energy per pulse were noted for the whole group at follow up vs baseline. The subgroup of patients with postsurgical gastroparesis required the most energy using the algorithm. In conclusion, an algorithmic approach to identify optimal stimulation parameters in GES for individual patients is associated with symptom improvement. Also, certain subgroups appear to have different energy parameters. Based on this preliminary data, the use of an algorithm for some patients with GES is feasible and may have potential for clinical application. A randomized‐controlled trial of different stimulation parameters for GES seems warranted.

Postinfectious gastroparesis related to autonomic failure: a case report

Abstract  Background and aim:  Severe dysautonomia may be secondary to viral infections, resulting in impaired autoimmune, cardiovascular, urinary and digestive dysfunction. Herein, we present a case of a 31‐year‐old white female patient who had severe gastroparesis related to autonomic failure following an episode of acute gastroenteritis. This seems to be the first report providing thorough assessment of the enteric and autonomic nervous system by analysis of full‐thickness small intestinal biopsies, cardiovagal testing and autopsy.

111 HYPERCOAGULABILITY IS FOUND IN A REMARKABLY HIGH PERCENTAGE (89%) OF PATIENTS WITH SEVERE GASTROPARESIS

Introduction Patients with severe gastrointestinal motility disorders often are found to have intravenous access clots or deep venous thrombosis, which can especially be difficult to manage, particularly if the patients require sustained intravenous access (IVA). We have previously reported that many patients who have IVA thrombosis have concomitant coagulation disorders. In this study, our goal was to determine the underlying prevalence of hypercoagulability in a series of patients with documented severe gastroparesis. Methods We studied 63 consecutive patients (10 male, 53 female, mean age 42 years) who had both symptoms of gastroparesis and documented disorders of gastric emptying in order to assess the prevalence of inherited and acquired coagulopathies in this group. All patients were being evaluated for a gastric neural stimulation device or had one placed previously. Patients underwent a hematologic interview and previously standardized measures of coagulation. Laboratory studies performed included measuring acquired defects of factor VII, factor VIII, fibrinogen, lupus anticoagulant panel, antiphospholipid antibody panel, homocysteine (in the setting of kidney disease), and activated protein resistance. The congenital defects measured were antithrombin III, protein C, protein S (total and free), factor II mutation, factor V Leiden, methylenetetrahydrofolate resistance (MTHFR), and homocysteine. Results Of the 63 patients, all but 7 (89%) were found to have detectable coagulation abnormalities. Twenty-five of the 63 (40%) patients had a documented history of abnormal clotting, including deep venous thrombosis, intravenous access thrombosis, and pulmonary embolism. All of the patients with a previous history of thrombosis were found to have detectable clotting abnormalities. No abnormalities in antithrombin III, protein C, or factor V Leiden were detected in this study group. Conclusion We conclude that there is a high prevalence of both acquired and congenital hypercoagulable defects in patients with gastroparesis that may predispose them to thrombosis. This unique finding warrants consideration of a coagulation evaluation in patients with severe gastroparesis, especially when those patients found to have underlying clotting abnormalities are placed in thrombophilic situations.

CYCLIC SYMPTOMS IN PATIENTS WITH GASTROPARESIS: DIFFERENCES FROM NONCYCLIC PATIENTS UNDERGOING GASTRIC ELECTRIC STIMULATION.: 308

Introduction Whereas most patients with the symptoms of gastroparesis (GP) have chronic symptoms, others have symptoms that are cyclic in nature. We investigated patients presenting with the symptoms of GP, most of whom underwent eventual placement of gastric electrical stimulation (GES), to see if patients with cyclic symptoms differed from those with No cyclic symptoms. Patients From a database of 345 consecutive patients seen, 48 patients (8 M, 40 F, mean age 41.5 years)-with the following diagnoses: 18 idiopathic, 27 diabetes mellitus, and 3 postsurgical disorders-presented with the symptoms of GP. Most patients were drug refractory and referred for possible GES. Patients were 35 (3 M, 32 F) with cyclic symptoms (Cyc) and 13 (1 M, 12 F) with no cyclic symptoms (NoCyc). Thirty-eight of 48 patients (25 Cyc and 13 NoCyc) underwent implantation of permanent GES, mean of 33 months. Results were compared by paired t -tests, baseline versus latest for GES patients, reported as mean ± SE. Results Cyc patients were similar to NoCyc patients with the exception of solid gastric emptying and health-related quality of life (HRQOL), both of which were more impaired in Cyc versus NoCyc patients. After GES placement (mean mo), the percentage improvement in all parameters (symptoms, GET, and HRQOL) was greater in Cyc than in NoCyc patients (Table). Conclusions Based on this sample, GP patients with cyclic symptoms respond better to GES than those with no cyclic symptoms. These preliminary results need confirmation in larger, prospective trials.

304 DOUBLE-BLINDED RANDOMIZED STUDY OF TEMPORARY GASTRIC ELECTRICAL STIMULATION: PRELIMINARY RESULTS OF THE ENDOSTIM STUDY (ENDOSCOPIC STIMULATION TEMPORARILY IMPLANTED MUCOSALLY).

Introduction Permanently implanted gastric electrical stimulation (GES) has been shown to be a successful therapy for many aspects of gastroparesis (GP). Recently, endoscopic temporary GES (GIE, 2005), has been advocated as a method to rapidly determine the possible beneficial effects of this therapy. However, temporary GES (Temp GES) has not been studied in a blinded manner. Patients We studied 58 patients (11 males, 47 females, mean age 46 years) with the symptoms of GP and an underlying diagnosis (idiopathic [ID], n = 38; diabetes mellitus (DM), n = 13; postsurgical [PS], n = 7) in a randomized placebo-controlled crossover study of temp GES as two consecutive 4-day sessions. Methods After baseline assessments of symptoms (including vomiting) and health-related quality of life (HRQOL), patients underwent endoscopic placement of Temp GES on day 1 and then had devices turned ON/OFF through day 4, when another assessment was done. Patients were crossed over to OFF/ON days 5 through day 8 when final assessments were performed. Results were compared by t-tests within and between groups and reported as mean ± SE. Results Twenty-eight patients had ON-OFF and 30 patients had OFF-ON; 45 of 58 patients finished all 8 days. When analyzed for all patients ON versus all patients OFF, both vomiting frequency and HRQOL improved significantly (p Conclusions This blinded comparison of temporary endoscopic GES is the first evidence-based study of its effectiveness. Further stratification of results from the EndoSTIM study should provide additional information about which gastroparesis patients may benefit most from temporary GES.

312 MORTALITY IN PATIENTS WITH GASTROPARESIS: A COMPARISON BETWEEN PATIENTS WITH AND WITHOUT DIABETES.

Introduction Gastroparesis (GP) is an often serious disorder of gastric neuromuscular function, but the long-term survival of GP is unknown. We reviewed two studies of GP patients with and without diabetes either on long-term antiemetic therapy or implanted with gastric electric stimulation (GES) devices to examine mortality. Studies The first study was of 32 GP patients, treated with ondansetron (Zofran) alone, promethazine (Phenergan) alone, or both, followed for up to 10 years (1992-2002). Six patients had diabetes mellitus and 26 had idiopathic GP. Although long-term antiemetic therapy was effective in controlling nausea and vomiting, four diabetic and four idiopathic GP patients had died over 10 years, a mortality rate of 66% compared with 15% in the idiopathic group. In the second, 156 of 214 patients with symptoms of drug-refractory GP were treated with GES devices over a period of 13 years (1992-2005). Patients were subdivided into three groups: 107 idiopathic group, 32 diabetic group, and 17 postsurgical GP patients, all receiving GES devices. At the latest follow-up (median 4 years for 5,568 patient-months), most patients implanted (135 of 156) were alive with intact devices, had significantly reduced GI symptoms, reported improved health-related quality of life, and had evidence of improved gastric emptying. A total of 26 of 214 patients (12.1%) died. Among patients with permanent device implantation, 21 of 156 died (13.4%); this included 5 of 32(15.6%) DM and 16 of 124 (12.9%) non-DM. Patients consented but not implanted served as controls: of these, 5 of 25 (20.0%) died, 4 of 5 with DM (80%) and 1 of 5 (20%) without DM. Cause of death was primarily due to underlying disease and was not determined to be directly related to the GES device in any patient. Death among patients implanted was similar to those not implanted for nondiabetic patients (16/124 = 12.9% vs 1/5 = 20%) but lower for GES diabetic patients (5/32 = 15.6% vs 4/5 = 80%; p Conclusions Data from two recent studies demonstrate a definite improvement in the symptoms of GP in diabetic patients with long-term antiemetic therapy as well as permanent GES devices. There appears to be a significantly higher mortality in diabetic patients compared with GP patients with idiopathic and postsurgical disease. The high long-term mortality in patients with diabetes mellitus suggests that GP may be a marker of severe systemic disease for certain patients. In addition, the implantation of a GES device in DM GP appears to be associated with a lower mortality.

306 IMPACT OF COMBINED GASTRIC AND SACRAL STIMULATORS ON UPPER/LOWER GASTROINTESTINAL AND URINARY SYMPTOMS.

Introduction Gastric electrical stimulation (GES) is available as a humanitarian use device for patients with the symptoms of gastroparesis and is effective in reducing gastrointestinal symptoms. We have previously shown that patients with gastric motor disorders often have coexisting abnormalities of the genitourinary system (Gastroenterology 1997;112:A737), which may now be treated with sacral electrical stimulation (SES), resulting in similar improvements in genitourinary symptoms. SES has been shown to be beneficial in controlling fecal incontinence and resistant idiopathic constipation. Patients We compared the results of therapy with GES and SES in 20 patients who were implanted with both devices. Data for 16 patients are complete for upper and lower gastrointestinal and urinary symptoms. Patients were 18 F, 2 M, mean age of 40 years, who had documented gastroparesis as well as bladder or other pelvic floor dysfunction. All 20 patients had received their GES before the SES. Methods Patients were evaluated at baseline and latest follow-up (median 4 years for GES and 2 years for SES). Scores of upper GI (GI: 0-4, TSS max 20), lower GI (GI: 0-4, TSS max 12 and BMs per day), and GU (GU: 0-3, UTSS, max 12) function were recorded. Results were compared by paired t-tests and reported as mean ± SE. Results All 16 patients improved both upper and lower GI and GU symptoms. Improvement in all parameters as nausea (2.75 vs 0.65), vomiting (3.98 vs 1.63), anorexia (3.48 vs 1.45), bloating (3.7 vs 1.98), abdominal pain (3.8 vs 1.4), and gastric total symptom score (TSS) (17.1 vs 7.1), leakage (1.74 vs 0.26), urinary urgency (1.74 vs 0.61), voiding difficulty (2.2 vs 0.38), number of pads used (1.08 vs 0.21) and urinary total symptom score (UTSS) (6.55 vs 1.13), fecal urgency (1.44 vs 1.0), constipation (2.81 vs 1.19), fecal total symptom score (5.0 vs 2.69), and number of BMs per day (1.12 vs 1.87) were statistically significant (Table). Conclusions The combination of GES and SES appears to be both safe and effective for patients with concomitant gastroparesis and bladder dysfunction, and SES improved coexistent fecal abnormalities as well.

307 MUCOSAL AMPLITUDE RATIO OF TEMPORARY ELECTROGASTROGRAPHY PREDICTS OUTCOME OF RESPONSE TO GASTRIC ELECTRICAL STIMULATION.

Introduction Gastric electrical stimulation (GES) is an accepted therapy for gastroparesis (GP) with chronic nausea and vomiting. Temporary GES is a new approach applying GES endoscopically via the gastric mucosa. We previously reported that the ratio of frequency to amplitude of the serosal EGG at the time of placement might correlate with outcome of permanent GES. We now investigated the hypothesis that the ratio of frequency to amplitude of the mucosal EGG (mEGG) at the time of temporary GES placement might predict outcome to therapy. Patients 149 patients (118 F, 31 M, mean age of 44 years) with the symptoms of GP and diagnosis: 82 idiopathic, 41 diabetic, and 26 postsurgical, underwent temporary GES (TempGES) as previously described (GIE, 2005). Methods Patients were assessed at baseline and after 3 days of TempGES in terms of symptoms of vomiting (V), nausea (N), and GI total symptom score (TSS). The average frequency (F), amplitude (A), frequency to amplitude ratio (MART), and subclasses of F/A (by low/high for each) were calculated and compared with the outcome by % V symptom change and by V change category as none, minimal, or marked; were compared by t-tests, correlation, and chi-square and reported as mean ± SE. Results After 3 days of TempGES, V score changed from 2.3 ± 0.1 to 0.5 ± 0.1, N score changed from 3.3 ± 0.1 to 1.2 ± 0.1, and TSS changed from 14.3 ± 0.3 to 5.3 ± 0.4 (all p Conclusions We conclude that mucosal recordings of EGG frequency and amplitude at the time of endoscopic electrode placement correlate with symptom outcomes of temporary GES.

185 A MULTICOMPONENT MODEL CAN PREDICT OUTCOME OF RESTRICTIVE SURGERY FOR OBESITY.

Introduction We previously reported that a multicomponent model of autonomic and enteric factors may correlate with ultimate weight loss or gain after restrictive obesity surgery (Neurogastroenterol Motil abstract, 2005). Patients We have followed 39 patients (10 gainers, 29 losers), 4 male, 35 female, mean age = 37.2 years, who underwent vertical banded gastroplasty, for up to 15 years post surgery, evaluating ultimate weight loss (losers) or gain (gainers). Patients were compared with their latest available weight vs baseline weight. Baseline autonomic (adrenergic: photophlethesmotic VC and PAR and cholinergic: EKG RRI) and enteric measures (electrogastrogram: EGG), as previously reported, above, were compared with latest weight. Methods We performed a discriminant function analysis to investigate whether a patients EGG, PAR, RRI, and VC values could be used to classify that patient as a loser or gainer following weight control surgery. The patients were divided into two groups (the gold standard for gainers or losers). The discriminant criterion derived from the data for patients in the two groups was applied to each patients EGG, PAR, RRI, and VC values to determine whether these measurements separated the patients into their gold standard category. Results A model based on baseline measures successfully predicted ultimate weight gain in 8/10 (80%) patients who subsequently gained weight and weight loss in 24/29 (83%) patients who subsequently lost weight for a total correct classification rate of 32/39 (82%) (see table below). Conclusions A multicomponent model shows that baseline measures can predict ultimate weight outcome from restrictive obesity surgery. Table 4-Component Model