William J. Snape

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.

Sacral nerve stimulation for fecal incontinence: Results of a 120-patient prospective multicenter study

Background:Sacral nerve stimulation has been approved for use in treating urinary incontinence in the United States since 1997, and in Europe for both urinary and fecal incontinence (FI) since 1994. The purpose of this study was to determine the safety and efficacy of sacral nerve stimulation in a large population under the rigors of Food and Drug Administration-approved investigational protocol. Methods:Candidates for SNS who provided informed consent were enrolled in this Institutional Review Board-approved multicentered prospective trial. Patients showing ≥50% improvement during test stimulation received chronic implantation of the InterStim Therapy (Medtronic; Minneapolis, MN). The primary efficacy objective was to demonstrate that ≥50% of subjects would achieve therapeutic success, defined as ≥50% reduction of incontinent episodes per week at 12 months compared with baseline. Results:A total of 133 patients underwent test stimulation with a 90% success rate, and 120 (110 females) of a mean age of 60.5 years and a mean duration of FI of 6.8 years received chronic implantation. Mean follow-up was 28 (range, 2.2–69.5) months. At 12 months, 83% of subjects achieved therapeutic success (95% confidence interval: 74%–90%; P < 0.0001), and 41% achieved 100% continence. Therapeutic success was 85% at 24 months. Incontinent episodes decreased from a mean of 9.4 per week at baseline to 1.9 at 12 months and 2.9 at 2 years. There were no reported unanticipated adverse device effects associated with InterStim Therapy. Conclusion:Sacral nerve stimulation using InterStim Therapy is a safe and effective treatment for patients with FI.

Colonic myoelectrical activity in irritable-bowel syndrome. Effect of eating and anticholinergics.

To determine the effect of a standard meal on colonic myoelectrical and motor activity in the irritable-bowel syndrome and to determine the effect of a single dose of an oral anticholinergic drug (clidinium bromide) on this response, we studied 10 patients. These patients showed a prolonged increase in both colonic spike (P less than 0.05) and motor activity (P less than 0.05) after eating as compared to normal subjects. Clidinium did not affect the frequency of colonic slow waves or the basal colonic spike and motor activity. However, the anticholinergic reduced the prolonged postprandial colonic spike and motor response in the patients and also reduced the postprandial increase in colonic contractions at 3 cycles per minute (P less than 0.05). These studies indicate that patients with the irritable-bowel syndrome show an abnormally prolonged post-prandial increase in colonic spike and motor activity. An anticholinergic drug reduces the duration and the magnitude of this abnormal colonic response.

COLONIC MYOELECTRIC ACTIVITY IN THE IRRITABLE BOWEL SYNDROME

Although the irritable bowel syndrome has been characterized as an abnormality in colonic motor activity occurring in response to certain stimuli, the etiology of this abnormality is unclear. The purpose of this study was to compare colonic myoelectric and motor activity in normal subjects and in patients with the irritable bowel syndrome. Myoelectric activity was recorded using a bipolar electrode clipped to the mucosa of the rectal and rectosigmoid areas. Basic electrical rhythm (BER), spike potential activity, and intraluminal pressure were recorded in both groups. Two types of BER were observed. The major component of the BER had a frequency of approximately 6 cycles per min, whereas the minor component had a frequency of approximately 3 cycles per min. Although both types of BER were recorded in the two groups, thitable bowel syndrome. The 3 cycles per min activity was present as 44.1 +/- 1.3% of the total BER in the irritable bowel syndrome, as compared with 10.0 +/- 1.6% in the normal group (P less than 0.001). Basal spike potential and motor activity were similiar in both groups. Because it had been demonstrated previously that colonic responsiveness to certain stimuli was increased during the slower frequency BER, it is suggested that the abnormalities in colonic motor response reported in the irritable bowel syndrome may be related to this difference in colonic BER.

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.

Evidence that Abnormal Myoelectrical Activity Produces Colonic Motor Dysfunction in the Irritable Bowel Syndrome

Although the irritable bowel syndrome is characterized as an abnormality in colonic motor activity occurring in response to certain stimuli, the etiology of this disorder is unclear. The purpose of this study is to determine the relationship of altered slow wave activity and the abnormal motility of the distal colon seen in patients with the irritable bowel syndrome. Myoelectrical activity was recorded using a bipolar electrode clipped to the distal colonic mucosa and motor activity was measured by perfused catheters. Colonic slow waves and contractions were present at two frequencies, 6 and 3 cycles per min. The slow wave frequency seemed to determine the frequency of colonic motor activity. Patients with the irritable bowel syndrome had increased 3-cycle per min slow wave activity in the basal state (P less than 0.001). However, no difference in basal 3-cycle per min motor activity was present between the two groups (P greater than 0.05). When colonic motor activity was increased with cholecystokinin or pentagastrin, patients with irritable bowel syndrome showed a marked increase in 3-cycle per min contractile activity, occurring simultaneously with 3-cycle per min slow wave activity. These studies suggest that increased colonic 3-cycle per min slow wave activity in patients with the irritable bowel syndrome may be the basic abnormality that leads to colonic motor dysfunction in response to various physiological stimuli.

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.

Achalasia Secondary to Carcinoma: Manometric and Clinical Features

The clinical and diagnostic features of a secondary type of achalasia of the esophagus are described in seven patients with various types of malignancies. Patients with secondary achalasia presented with dysphagia of short duration and marked weight loss; mean age was 64 years. Esophageal manometry showed features identical to those of idiopathic primary achalasia: aperistalsis, poor lower esophageal sphincter relaxation, and elevated sphincter pressure. Endoscopy and barium swallow showed evidence of a tumor in only two cases. Various types of malignancies may produce a secondary form of achalasia that has diagnostic features identical to those of primary achalasia and is best identified by its clinical presentation.

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.

Characteristics of Patients with Chronic Unexplained Nausea and Vomiting and Normal Gastric Emptying

BACKGROUND & AIMS Chronic nausea and vomiting with normal gastric emptying is a poorly understood syndrome; we analyzed its characteristics. METHODS We collected and analyzed data from 425 patients with chronic nausea and vomiting, enrolled at 6 centers by the Gastroparesis Clinical Research Consortium in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry. RESULTS Among the patients, 319 (75%) had delayed emptying, defined by the results of a standardized, low-fat meal, and 106 had normal gastric emptying. Patients with or without delayed emptying did not differ in age, sex, or race, although those with normal gastric emptying were less likely to be diabetic. Symptom severity indexes were similar between groups for nausea, retching, vomiting, stomach fullness, inability to complete a meal, feeling excessively full after meals, loss of appetite, bloating, and visibly larger stomach. There were no differences in health care utilization, quality of life indexes, depression, or trait anxiety scores. However, state anxiety scores were slightly higher among patients with delayed gastric emptying. Total gastroparesis cardinal symptom index scores were not correlated with gastric retention after 2 or 4 hours in either group. Patients with the syndrome were not adequately captured by the stand-alone criteria for the Rome III diagnoses of chronic idiopathic nausea and functional vomiting. With rare exceptions, the diagnosis remained stable after a 48-week follow-up period. CONCLUSIONS Patients with nausea and vomiting with normal gastric emptying represent a significant medical problem and are, for the most part, indistinguishable from those with gastroparesis. This syndrome is not categorized in the medical literature--it might be a separate clinical entity.