Steven Kantor

Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy

Abstract  Gastric emptying of digestible solids occurs after trituration of food particles. Non‐digestible solids are thought to empty with phase III of the migrating motor complex (MMC). The aim of this study was to determine if a non‐digestible capsule given with a meal empties from the stomach with return of the fasting phase III MMC or during the fed pattern with the solid meal. Fifteen normal subjects underwent antroduodenal manometry and ingestion of a radiolabelled meal and SmartPill wireless pH and pressure capsule. In five subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radiolabelled water. The SmartPill emptied from the stomach within 6 h in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 ± 22 min) correlated strongly with time to the first phase III MMC (239 ± 23 min; r = 0.813; P < 0.01) and correlated moderately with solid‐phase gastric emptying (r = 0.606 with T‐50% and r = 0.565 with T‐90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In five subjects, the SmartPill emptied with isolated distal antral contractions. In five subjects ingesting only water, SmartPill gastric residence time (92 ± 44 min) correlated with the time to the first phase III MMC (87 ± 30 min; r = 0.979; P < 0.01). The non‐digestible SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid‐phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non‐digestible solid.

Treatment of idiopathic gastroparesis with injection of botulinum toxin into the pyloric sphincter muscle.

OBJECTIVES:We aimed to determine if botulinum toxin injection into the pyloric sphincter improves gastric emptying and reduces symptoms in patients with idiopathic gastroparesis.METHODS:Patients with idiopathic gastroparesis not responding to prokinetic therapy underwent botulinum toxin (80–100 U, 20 U/ml) injection into the pyloric sphincter. Gastric emptying scintigraphy was performed before and 4 wk after treatment. Total symptom scores were obtained from the sum of eight upper GI symptoms graded on a scale from 0 (none) to 4 (extreme).RESULTS:Ten patients were entered into the study. The mean percentage of solid gastric retention at 4 h improved from 27 ± 6% (normal < 10%) before botulinum toxin injection into the pylorus to 14 ± 4% (p = 0.038) 4 wk after treatment. The symptom score decreased from 15.3 ± 1.7 at baseline to 9.0 ± 1.9 (p = 0.006) at 4 wk, a 38 ± 9% decrease. Improvement in symptoms tended to correlate with improved gastric emptying of solids (r = 0.565, p = 0.086).CONCLUSIONS:This initial pilot study suggests that botulinum toxin injection into the pylorus in patients with idiopathic gastroparesis improves both gastric emptying and symptoms.

Egg Labeling Methods for Gastric Emptying Scintigraphy Are Not Equivalent in Producing a Stable Solid Meal

A wide range of radiolabeled test meals have been used for gastric emptying scintigraphy. The purpose of this study was to test whether 99mTc-sulfur colloid−labeled liquid egg white is as stable as 2 fresh whole eggs labeled with 99mTc-sulfur colloid and whether the cooking method is important. Methods: Whole eggs and liquid egg white were mixed with 99mTc-sulfur colloid and cooked by either microwaving or frying on a griddle. The cooked eggs were tested for breakdown after 2 and 4 h of incubation in gastric fluid or HCl. Results: Labeled liquid egg white, prepared by either method of cooking, exhibited less breakdown in gastric fluid than whole eggs. Whole eggs cooked in the microwave exhibited significantly more breakdown than liquid egg white. Conclusion: 99mTc-Sulfur colloid binds better to egg whites compared with whole eggs. These results emphasize the need to evaluate the stability of new radiolabeled test meal preparations, including the method of cooking.

Regional gastric emptying abnormalities in non-ulcer dyspepsia (NUD) and gastroesophageal reflux disease (GERD)

Purpose: To determine whether abnormal proximal (P) and|[sol]|or distal (D) gastric motor dysfunction are present in non-ulcer dyspepsia (NUD) and gastroesophageal reflux disease (GERD).

Regional Analysis of Gastric Emptying Scintigraphy Provides Better Correlation of Dyspeptic Symptoms With Abnormal Gastric Emptying

Ghrelin, a 28-amino acid peptide produced by the stomach, is the natural ligand for the GHS-1a receptor and may have the potential to treat clinical conditions associated with impaired gastric motility and energy balance. Administration of ghrelin promotes gastric motility in mice, rats, dogs and humans, and also increases body weight by increasing food intake, inducing positive energy balance, and increasing growth hormone secretion. RM131 (formerly reported as BIM-28131) is a novel pentapeptide that acts as a potent ghrelin agonist. The aim of the present study was to compare the gastroprokinetic effects of RM131with human ghrelin and small molecule GHS-1aR agonists including ipamorelin, anamorelin and MK-677, in a model of post-operative ileus. Male Sprague Dawley rats were fasted for 24 h with free access to water. Gastric ileus was induced by laparotomy under anesthesisa.. Abdominal muscles and skin were then closed with sutures and the animals were allowed to recover for 2.5 hours. At that time, to further worsen the symptoms of ileus, the animals were treated with morphine (4mg/kg, sc). Test compounds were administered by subcutaneous injection 30 min after morphine administration, and 15 minutes before receiving a phenol red-markedmeal by esophageal gavage. The effect on gastric emptyingwas determined by measuring the residual marked meal in the stomach after sacrifice. Laparotomy alone induced a 35% decrease in gastic emptying, while the additional administration of morphine further decreased gastric emptying to 61%, as compared with sham-operated, saline-injected controls. Administration of RM-131 resulted in a progressive, dose-related reversal of the laparotomy/morphine-induced ileus, reaching full restoration of gastric emptying by a dose of 0.3nmole/kg. Human ghrelin and anamorelin were also fully efficacious in restoring gastric emptying, but were 130and 100-fold less potent than RM-131, respectively. MK-677 and ipamorelin were only partially effective in restoring gastric emptying, even at doses as high as 100nmole/kg. These results demonstrate that RM-131, a potent agonist of the GHS-1a receptor, is highly efficacious in inducing increased gastric emptying in a model of gastric ileus induced by bothmorphine and laparatomy. RM-131 is being developed for the treatment of disorders of GI motility, including POI and diabetic gastroparesis by Rhythm Pharmaceuticals (Boston, MA).