Warren Starkebaum

Gastric electrical stimulation for medically refractory gastroparesis

BACKGROUND & AIMS This study investigated the efficacy of gastric electrical stimulation for the treatment of symptomatic gastroparesis unresponsive to standard medical therapy. METHODS Thirty-three patients with chronic gastroparesis (17 diabetic and 16 idiopathic) received continuous high-frequency/low-energy gastric electrical stimulation via electrodes in the muscle wall of the antrum connected to a neurostimulator in an abdominal wall pocket. After implantation, patients were randomized in a double-blind crossover design to stimulation ON or OFF for 1-month periods. The blind was then broken, and all patients were programmed to stimulation ON and evaluated at 6 and 12 months. Outcome measures were vomiting frequency, preference for ON or OFF, upper gastrointestinal tract symptoms, quality of life, gastric emptying, and adverse events. RESULTS In the double-blind portion of the study, self-reported vomiting frequency was significantly reduced in the ON vs. OFF period (P < 0.05) and this symptomatic improvement was consistent with the significant patient preference (P < 0.05) for the ON vs. OFF period determined before breaking the blind. In the unblinded portion of the study, vomiting frequency decreased significantly (P < 0.05) at 6 and 12 months. Scores for symptom severity and quality of life significantly improved (P < 0.05) at 6 and 12 months, whereas gastric emptying was only modestly accelerated. Five patients had their gastric electrical stimulation system explanted or revised because of infection or other complications. CONCLUSIONS High-frequency/low-energy gastric electrical stimulation significantly decreased vomiting frequency and gastrointestinal symptoms and improved quality of life in patients with severe gastroparesis.

Gastric electrical stimulation is associated with improvement in pancreatic exocrine function in humans.

Objective: To define the possible effects of gastric electrical stimulation (GES) for gastroparesis on pancreatic function, we performed 2 related human studies. Methods: Fecal elastase values were compared in 2 patient groups: (1) GES devices ON and (2) GES devices OFF and (2) in 3 control groups: (1) no response (NR) to prokinetic medications, (2) positive response (RES) to medications, and (3) normal controls. Polypeptide levels in 7 of 9 GES patients with device ON and OFF, elastase results, GI symptoms (TSS), and heart rate variability (HRV) were compared by paired t tests and/or ANOVA and reported as mean ± SE. Results: Elastase was different for GES-ON and OFF (508.0 ± 92.2 vs. GES-OFF 378.6 ± 87.4, P < 0.05). Elastase was lower in medication NR and RES than in normal controls. Postprandial pancreatic polypeptide was greater with GES ON than OFF (P = 0.07). HRV revealed a lower percentage of change with device ON versus OFF (44.2 ± 5.5 vs. 48.5 ± 5.2, P = 0.08) and lower TSS with ON versus OFF (15.9 ± 4.5 vs. 25.7 ± 5.3, P < 0.05). Conclusions: GES improves exocrine pancreatic release, effects autonomic control, and improves GI symptoms, suggesting a possible role for GES in the treatment of pancreatic insufficiency associated with gastroparesis.

Food intake and body weight responses to intermittent vs. continuous gastric electrical stimulation in diet-induced obese rats.

BackgroundGastric electrical stimulation (GES) has recently been introduced as a potential therapy for the treatment of obesity. The main challenge for the new generation of devices is to achieve desired clinical outcomes at a suitably low level of energy consumption. The aim of this study is to compare the effectiveness of GES with continuous and intermittent duty cycles in reducing food intake and body weight in diet-induced obesity-prone rats.MethodsIn macro duty cycle experiment, 40 rats were divided into groups to receive a sham GES, continuous GES, or intermittent GES (15 min On–45 min Off or 15 min On–15 min Off) for 28 days. In micro duty cycle experiment, 18 rats received cross-over treatment of continuous stimulation, 60 % time cycle or 40 % time cycle. Food intake, body weight, gastric emptying and ghrelin level were measured to evaluate the effect of different GES.ResultsGES with macro duty cycle intensity-dependently reduced mean daily food intake increase by 18.6, 10.2 and -6.0 % compared to 42.7 % with sham GES and body weight gain by 6.1 %, 3.4 and -0.8 % compared to 5 % with sham GES. Daily food intake decreased with increasing micro duty cycle intensity, averaging 16.5, 15.6 and 13.7 g/day under 40 % cycle, 60 % cycle and continuous stimulation respectively. Gastric emptying was intensity-dependently delayed by GES. GES has no effect in modulating plasma ghrelin level.ConclusionsGES energy-dependently reduces food intake, body weight and gastric emptying. Peripheral modulation of plasma ghrelin level is not related to the GES effects.

Temporary Endoscopic Stimulation in Gastroparesis-like Syndrome.

Background/Aims Gastroparesis-like syndrome (GLS) is defined as gastroparesis-like symptoms with normal gastric scintigraphy. While the efficacy of gastric electrical stimulation (GES) in gastroparesis is well known, the utility of GES in GLS is largely unknown. Our aim was to clarify the role of GES in GLS. We implanted consecutive patients with symptoms of gastroparesis with temporary gastric electrical stimulation and observed changes in gastric scintigraphy and total symptom score. Methods Five hundred and fifty-one patients suffering from symptoms of gastroparesis (nausea, vomiting, bloating/distension, anorexia/early satiety, and abdominal pain) with negative endoscopy underwent gastric scintigraphy with analysis of 1) solid radio-nuclide gastric emptying at 1, 2, and 4 hours (% remaining); 2) area under the gastric emptying curve (AUC) at 1, 2, and 4 hours; and 3) total gastric emptying test (GET) (the sum of 1, 2, and 4 hour values). Patients were stratified into: delayed gastric emptying, normal gastric emptying, and rapid gastric emptying (Appendix). Of the 551 patients in the larger cohort, 379 had implantation of temporary gastric electrical stimulation (tGES). Gastrointestinal symptoms and gastric emptying were com -pared pre and post tGES implantation. Results After tGES, 2 hour gastric retention decreased (P < 0.01) for the delayed patients, and increased (P < 0.001) for normal and rapid patients. These changes were accompanied by improvements (P < 0.001) in vomiting, nausea, and total symptom scores in all 3 subgroups. Conclusions Gastric electrical stimulation may be an effective therapy for treating the symptoms of gastroparesis with normal gastric emptying. Further exploration of endoscopic electrical stimulation as a treatment for gastroparesis-like symptoms with non-delayed gastric emptying is needed.

Gastric electrical stimulation is associated with increased pancreatic exocrine secretion measured by pancreatic elastase

Hereditary pancreatitis (HP)is an autosomal dominant disorder with incomplete penetrance. It is characterized by recurrent episodes of severe abdominal pain which often presents in early childhood. A mutation in the cationic trypsinogen gene has been identified in this disease. Medical management of HP at times may be different. In non-hereditary pancreatitis, the approach to management is tailored towards the individual etiology, (sphincter of Oddi dysfunction, common bile duct stones, ect.) Aim: To determine if ERCP therapeutic intervention has any role in resolving the frequency of pain in HP. Methods: We have evaluated, retrospectively using a computer data base retrieval system, a series of nine pts who had documented, by history, familial pancreatitis. All of the pts reported pain or recurrent abdominal pain on initial presentation. They reported multiple hospitalizations prior to the initial presentation per acute pancreatitis. Five of 9 pts had pancreatic duct (PD) stone. Four out of 9 pts had a PD stricture. Two of 9 had both PD stricture and stones. Two of 9 pts had no stones or strictures, but did have blunting of the terminal branches of the PD, consistent with chronic pancreatitis. Results: ERCP outlined the PD in all pts, Only those pts with PD stones or PD stricture had improvement with either endoscopic sphincterotomy, PD stent placement or stone retrieval. Two of 9 pts had no PD stones or strictures and did not have any symptomatic improvement with ERCP intervention as noted by no significant change in frequency of abdominal pain or hospitalizations. Conclusion: Preliminary results have shown that a therapeutic ERCP is only helpful when there are structural defects such as pancreatic duct strictures or pancreatic duct stones. In the absence of such structural defects therapeutic intervention may have little benefit. 5295