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.

Does grading the severity of gastroparesis based on scintigraphic gastric emptying predict the treatment outcome of patients with gastroparesis?

OBJECTIVES: The objectives of this study were as follows: (1) Whether gastric emptying is different between gastroparesis (GP) patients responding or not responding to standard medical therapy; (2) Identifying if mild, moderate, and severe degrees of gastroparesis based on the scintigraphic gastric emptying test (GET) can predict treatment responses for GP of diabetic (DM) and idiopathic (ID) origin. METHODS: A total of 165 patients (119 F) diagnosed with GP [126 (76%) DM, 39 (24%) ID etiology] failed medical treatment and required the gastric electrical stimulation (GES) device (GES group). In addition, 112 patients (89 F) [37 (33%) DM, 75 (67%) ID] with GP who symptomatically responded to medical therapies are the comparison group (MED GP). All patients underwent a standardized scintigraphic GET consisting of low-fat (2%) isotope labeled egg beaters meal of 250 kcal. We also analyzed the GET data to find cut-off points for different degrees of GP and identified mild (11-20% retention), moderate (21-35%), and severe gastroparesis (>35%) based on percent retention of isotope at 4 h. RESULTS: Overall gastric retention at 4 h was significantly greater in the GES group (45±1.9%) than MED GP (30±2%) (p<0.001). The distribution severity of the GET was different in GES-treated patients than MED treated (p<0.001). In the diabetics, 57% of GES patients retained >35% after 4 h (severe) similar to 43% in the DM MED group. However, 50% of the ID GES patients had retention>35% at 4 h significantly more than only 17% of ID MED GP. Significantly more ID patients who responded to medical therapy had mild gastroparesis and significantly more requiring GES had severe GET (p<0.05). CONCLUSIONS: (1) GET in patients whose GP symptoms were refractory to standard medical therapy and required GES was significantly slower than in GP patients whose symptoms responded to medical therapy. (2) Stratifying GET into mild, moderate, and severe degrees of gastric retention does not predict whether a medical or surgical approach will be better to control the symptoms of diabetic GP but does correlate with treatment for the idiopathic GP subgroup.

Significant increase of esophageal mucin secretion in patients with reflux esophagitis after healing with rabeprazole: its esophagoprotective potential.

Esophageal mucin secretion in patients with reflux esophagitis (RE) is significantly impaired. Rabeprazole augments gastric mucin secretion. We have studied, therefore, the effect of rabeprazole on esophageal mucin secretion in patients with RE. The study was conducted in 15 patients with RE treated with rabeprazole (20 mg QD) for 8 weeks. Esophageal secretions were collected during consecutive infusions of initial NaCl, HCl/Pepsin (HCl/P), and a final NaCl, using a specially designed esophageal catheter, before and after therapy. Mucin was measured using standard methodology. After rabeprazole administration esophageal mucin concentration as well as secretion increased during perfusion with initial saline (P < 0.01), HCl/P (P < 0.02), and concluding saline (P < 0.001). Stimulation of esophageal mucin secretion by rabeprazole may indicate that the mechanisms governing its secretion are similar to those implicated in gastric mucin output. Enhancement of esophageal mucin secretion by rabeprazole may translate into esophagoprotective potential in patients with reflux esophagitis.

Significant enhancement of esophageal pre-epithelial defense by tegaserod: implications for an esophagoprotective effect.

BACKGROUND & AIMS: Tegaserod, a serotonin 5-hydroxytryptamine (5-HT)4 receptor agonist, is thought to stimulate intestinal secretions. The aim of the current study was to assess the effect of tegaserod vs placebo on salivary and esophageal protective factors in patients with gastroesophageal reflux disease (GERD). METHODS: This study was a randomized, double-blind, placebo-controlled, cross-over trial in 38 GERD patients treated with tegaserod 6 mg twice a day vs placebo. Salivary samples were collected basally and during mastication. In addition, in 32 GERD patients, salivary and esophageal secretions also were collected during infusion of NaCl, HCl/pepsin, and NaCl in a consecutive fashion using a specially designed esophageal catheter. Saliva and esophageal perfusates were assessed for the pH, volume, content of buffers, protein, mucin, epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and prostaglandin E (PGE)2 and analyzed statistically. RESULTS: Salivary flow rates during administration of tegaserod increased over corresponding values during both basal conditions (P < .01) and mastication (P < .001). The rate of secretion of salivary bicarbonate and nonbicarbonate buffers also increased in basal conditions (P < .001 and P < .01, respectively) and during mastication (P < .05 and P = .05). Salivary EGF increased during mastication (P < .05), whereas PGE2 and TGF alpha increased in basal conditions (P < .05 and P < .01). Esophageal perfusate volumes increased during administration of tegaserod in basal conditions (P < .05), whereas esophageal EGF secretion increased after mucosal exposure to HCl/pepsin and subsequent final perfusion with NaCl (P < .05). CONCLUSIONS: Significant stimulatory impact of 5-HT4 agonist on several salivary protective factors as well as esophageal EGF secretion may have esophagoprotective implications in patients with GERD and may help to address new therapies in the future.

Further experience with gastric stimulation to treat drug refractory gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) has been introduced for patients with gastroparesis refractory to pharmacological therapy. METHODS: From April 1998 until November 2001, 55 patients underwent GES implantation at Kansas University Medical Center. All patients had prolonged gastric retention of a solid meal by scintigraphy at baseline. The etiologies were diabetes mellitus in 39, related to previous surgery in 9, and idiopathic in 7. Symptoms were graded using a 5-point scale and quality of life was assessed with the SF-36 questionnaire. Body mass index and nutritional parameters were monitored. Hemoglobin A1C was measured in the diabetic patients. RESULTS: Total symptom scores and the physical and mental composite scores of quality of life improved significantly. On average, gastric emptying did not change. Body mass index and body weight increased significantly. And days spent in hospital admissions were significantly decreased. At 1 year, diabetic patients experienced reduced hemoglobin A1C. Four devices were removed. One patient died of a pulmonary embolus postoperatively. CONCLUSIONS: In a large series of patients with gastroparesis, GES significantly improved symptoms and quality of life.