William L. Hasler

Consensus recommendations for gastric emptying scintigraphy: A joint report of the American neurogastroenterology and motility society and the society of nuclear medicine

This consensus statement from the members of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine recommends a standardized method for measuring gastric emptying (GE) by scintigraphy. A low-fat, egg-white meal with imaging at 0, 1, 2, and 4 h after meal ingestion, as described by a published multicenter protocol, provides standardized information about normal and delayed GE. Adoption of this standardized protocol will resolve the lack of uniformity of testing, add reliability and credibility to the results, and improve the clinical utility of the GE test.

Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma

BACKGROUND Patients with scleroderma may have abnormal motility of the small intestine, with pseudoobstruction and bacterial overgrowth. Standard stimulatory agents are often ineffective in such patients. Because the somatostatin analogue octreotide evokes intestinal motor activity in normal subjects, we hypothesized that it might increase motility in patients with scleroderma. METHODS We studied the effects of octreotide on intestinal motility and plasma motilin concentrations in five fasting patients with scleroderma who had bacterial overgrowth and in six fasting normal subjects. The motor effects of octreotide were correlated with its effects on abdominal symptoms and bacterial overgrowth as determined by the level of breath hydrogen excretion. RESULTS In the normal subjects, octreotide (10 micrograms subcutaneously) increased the mean (+/- SD) frequency of intestinal migrating complexes, which reflect intestinal motility, from 1.5 +/- 1.0 to 4.1 +/- 1.1 every three hours. In the patients with scleroderma, who had no spontaneous migrating complexes, octreotide (100 micrograms) induced 3.6 +/- 2.3 complexes every three hours. These complexes propagated at the same velocity and had two-thirds the amplitude of the spontaneous complexes in normal subjects. Plasma motilin concentrations, which were higher in the patients with scleroderma (229 +/- 74 pmol per liter) than in the normal subjects (112 +/- 37 pmol per liter), were inhibited by octreotide, suggesting that intestinal activity evoked by octreotide is independent of motilin. Treatment of the patients with scleroderma with octreotide (50 micrograms every evening) for three weeks reduced breath hydrogen excretion while they were fasting from 25 +/- 5 to 4 +/- 2 ppm (P = 0.001) and breath hydrogen excretion after they ingested 50 g of glucose from 46 +/- 24 to 8 +/- 7 ppm (P = 0.015); these reductions were accompanied by a significant decrease in nausea, bloating, and abdominal pain and by less frequent emesis. CONCLUSIONS Octreotide stimulates intestinal motility in normal subjects and in patients with scleroderma. In such patients, the short-term administration of octreotide reduces bacterial overgrowth and improves abdominal symptoms. This agent may be useful for the treatment of intestinal dysmotility in patients with scleroderma.

Measurement of gastrointestinal motility in the GI laboratory

Current tests of gastric and small intestinal motor function provide relevant physiological information, but their clinical utility is controversial. This article reviews the current procedures, indications, significance, pitfalls, and guidelines for gastrointestinal motility measurements by scintigraphy, gastroduodenojejunal manometry, and surface electrogastrography in humans. Methods included review of literature and discussions in closed and open fora among investigators, including presentations for peer review at focused (Iowa City American Motility Society Symposium, December 1995) and national meetings (American Gastroenterological Association, May 1996, and American Motility Society, September 1996). The current tests are generally complementary; scintigraphy is typically the first test in the evaluation of gastric motor function and often confirms the clinical suspicion of dysmotility. Manometry identifies patterns suggestive of myopathy, neuropathy, or obstruction but may be most helpful when it shows entirely normal findings, because manometry helps in part to exclude dysmotility as a cause of symptoms. Electrogastrography may identify dysrhythmias or failure of signal power to increase postprandially; rhythm abnormalities may be independent of impaired emptying among dyspeptic patients. The best validated and clinically most significant results pertain to transit tests; manometry may contribute importantly to the diagnostic process; and the significance of electrogastrography remains to be fully elucidated.

Treatment of gastroparesis: a multidisciplinary clinical review

Abstract  This clinical review on the treatment of patients with gastroparesis is a consensus document developed by the American Motility Society Task Force on Gastroparesis. It is a multidisciplinary effort with input from gastroenterologists and other specialists who are involved in the care of patients with gastroparesis. To provide practical guidelines for treatment, this document covers results of published research studies in the literature and areas developed by consensus agreement where clinical research trials remain lacking in the field of gastroparesis.

Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects

Background  Gastric emptying scintigraphy (GES) using a radio‐labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET).

Electrogastrography: a document prepared by the gastric section of the American Motility Society Clinical GI Motility Testing Task Force

Abstract The objective of this document is to present the consensus opinion of the American Motility Society Clinical GI Motility Testing Task Force on the performance and clinical utility of electrogastrography (EGG). EGG is a non‐invasive means of recording human gastric myoelectrical activity or slow waves from cutaneous leads placed over the stomach. In healthy volunteers, EGG tracings exhibit sinusoidal waveforms with a predominant frequency of 3 cycles per minute (cpm). Clinical studies have shown good correlation of these cutaneous recordings with those acquired from serosally implanted electrodes. The amplitude of the EGG waveform increases with ingestion of caloric or non‐caloric meals. Some patients with nausea, vomiting, or other dyspeptic symptoms exhibit EGG rhythm disturbances or blunting of meal‐evoked EGG signal amplitude increases. These abnormalities correlate to some degree with delayed gastric emptying of solids. In selected patients, EGG may be complementary to gastric emptying testing. To date, no therapies have convincingly demonstrated in controlled studies that correcting abnormalities detected by EGG improves upper gastrointestinal symptoms. Proposed clinical indications for performance of EGG in patients with unexplained nausea, vomiting and dyspeptic symptoms must be validated by prospective controlled investigations.

Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies

Background  Disorders of gastrointestinal (GI) transit and motility are common, and cause either delayed or accelerated transit through the stomach, small intestine or colon, and affect one or more regions. Assessment of regional and/or whole gut transit times can provide direct measurements and diagnostic information to explain the cause of symptoms, and plan therapy.

Cellular Changes in Diabetic and Idiopathic Gastroparesis

BACKGROUND & AIMS Cellular changes associated with diabetic and idiopathic gastroparesis are not well described. The aim of this study was to describe histologic abnormalities in gastroparesis and compare findings in idiopathic versus diabetic gastroparesis. METHODS Full-thickness gastric body biopsy specimens were obtained from 40 patients with gastroparesis (20 diabetic) and matched controls. Sections were stained for H&E and trichrome and immunolabeled with antibodies against protein gene product (PGP) 9.5, neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide, substance P, and tyrosine hydroxylase to quantify nerves, S100β for glia, Kit for interstitial cells of Cajal (ICC), CD45 and CD68 for immune cells, and smoothelin for smooth muscle cells. Tissue was also examined by transmission electron microscopy. RESULTS Histologic abnormalities were found in 83% of patients. The most common defects were loss of ICC with remaining ICC showing injury, an abnormal immune infiltrate containing macrophages, and decreased nerve fibers. On light microscopy, no significant differences were found between diabetic and idiopathic gastroparesis with the exception of nNOS expression, which was decreased in more patients with idiopathic gastroparesis (40%) compared with diabetic patients (20%) by visual grading. On electron microscopy, a markedly increased connective tissue stroma was present in both disorders. CONCLUSIONS This study suggests that on full-thickness biopsy specimens, cellular abnormalities are found in the majority of patients with gastroparesis. The most common findings were loss of Kit expression, suggesting loss of ICC, and an increase in CD45 and CD68 immunoreactivity. These findings suggest that examination of tissue can lead to valuable insights into the pathophysiology of these disorders and offer hope that new therapeutic targets can be found.

Mediation of hyperglycemia-evoked gastric slow-wave dysrhythmias by endogenous prostaglandins

BACKGROUND/AIMS Antral hypomotility and gastric dysrhythmias occur in diabetic gastroparesis. This study tested the hypothesis that acute hyperglycemia suppresses fed antral contractions and disrupts slow-wave rhythmicity via prostaglandin pathways. METHODS Six normal volunteers underwent electrogastrography and antroduodenal manometry under control, hyperglycemic clamp, and euglycemic, hyperinsulinemic clamp conditions before and after administration of indomethacin (50 mg orally three times daily for 3 days). RESULTS Hyperglycemic clamping to 230 mg/dL evoked a 4-fold increase in tachygastric activity and a 2.6-fold increase in arrhythmic activity (P < 0.05), whereas 140 and 175 mg/dL did not induce dysrhythmias. Antral motility indexes were reduced by 58% +/- 14% at 175 mg/dL and 70% +/- 8% at 230 mg/dL after a 750-kcal meal. Euglycemic, hyperinsulinemic clamping to insulin levels observed with the highest glucose infusions did not produce tachyarrhythmias or hypomotility. After indomethacin, hyperglycemic clamping to 230 mg/dL did not induce tachyarrhythmias. In contrast, indomethacin did not prevent the reduction in motility evoked by hyperglycemic clamping. CONCLUSIONS Acute hyperglycemia, but not hyperinsulinemia, inhibits fed antral motility and induces gastric dysrhythmias at higher plasma glucose levels. Induction of dysrhythmias, but not hypomotility, is dependent on endogenous prostaglandin synthesis. These findings offer insight into the myoelectric disturbances of diabetic gastroparesis and suggest a possible therapeutic role for prostaglandin synthesis inhibitors for gastric dysrhythmias in this condition.

Clinical Features of Idiopathic Gastroparesis Vary With Sex, Body Mass, Symptom Onset, Delay in Gastric Emptying, and Gastroparesis Severity

BACKGROUND & AIMS Idiopathic gastroparesis (IG) is a common but poorly understood condition with significant morbidity. We studied characteristics of patients with IG enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry. METHODS Data from medical histories, symptom questionnaires, and 4-hour gastric emptying scintigraphy studies were obtained from patients with IG. RESULTS The mean age of 243 patients with IG studied was 41 years; 88% were female, 46% were overweight, 50% had acute onset of symptoms, and 19% reported an initial infectious prodrome. Severe delay in gastric emptying (>35% retention at 4 hours) was present in 28% of patients. Predominant presenting symptoms were nausea (34%), vomiting (19%), an abdominal pain (23%). Women had more severe nausea, satiety, constipation, and overall gastroparesis symptoms. Patients who experienced acute-onset IG had worse nausea than those with insidious onset. Overweight patients had more bloating and gastric retention at 2 hours but less severe loss of appetite. Patients with severely delayed gastric emptying had worse vomiting and more severe loss of appetite and overall gastroparesis symptoms. Severe anxiety and depression were present in 36% and 18%, respectively. A total of 86% met criteria for functional dyspepsia, primarily postprandial distress syndrome. CONCLUSIONS IG is a disorder that primarily affects young women, beginning acutely in 50% of cases; unexpectedly, many patients are overweight. Severe delay in gastric emptying was associated with more severe symptoms of vomiting and loss of appetite. IG is a diverse syndrome that varies by sex, body mass, symptom onset, and delay in gastric emptying.