Pyloric sphincter characteristics using EndoFLIP® in gastroparesis. / Características del esfínter pilórico utilizando EndoFLIP® en gastroparesia.

INTRODUCTION AND AIMS: Pyloric sphincter abnormalities may be detected in gastroparesis. Botulinum toxin A (BoNT/A) injection into the pylorus has been used to treat gastroparesis with varying results. The aim of the present article was to assess whether pyloric sphincter characteristics using the endoscopic functional lumen imaging probe (EndoFLIP®) with impedance planimetry in patients with gastroparesis correlated with symptoms, gastric emptying, and therapeutic response to pyloric sphincter BoNT/A injection. METHODS: EndoFLIP® study was performed on patients undergoing gastroparesis treatment with BoNT/A. The gastroparesis cardinal symptom index (GCSI) was applied prior to treatment and at post-treatment weeks 2, 4, 8, and 12. RESULTS: Forty-four patients were enrolled (30 with idiopathic gastroparesis, 14 with diabetic gastroparesis). Smaller pyloric diameter, cross-sectional area (CSA), and distensibility correlated with worse vomiting and retching severity at baseline. Greater gastric retention tended to correlate with decreased CSA and pyloric distensibility. BoNT/A treatment resulted in a significant decrease in the GCSI score at 2 and 4 weeks after treatment, but not at post-treatment weeks 8 or 12. Nausea, early satiety, postprandial fullness, and upper abdominal pain improved up to 12 weeks, whereas loss of appetite, stomach fullness, and stomach visibly larger improved only up to 4 weeks. Retching and vomiting failed to improve. Greater pyloric compliance at baseline correlated with greater improvement in early satiety and náusea at 8 weeks and greater pyloric distensibility correlated with improvement in upper abdominal pain. CONCLUSIONS: EndoFLIP® characteristics of the pylorus provided important pathophysiologic information in patients with gastroparesis, in relation to symptoms, gastric emptying, and predicting the response to treatment directed at the pylorus.

Therapeutic response to domperidone in gastroparesis: A prospective study using the GCSI-daily diary.

Common symptoms of gastroparesis include nausea, vomiting, early satiety, postprandial fullness, and upper abdominal pain. Domperidone is used for treatment of gastroparesis. Daily symptom scoring may help document efficacy. AIM: To determine the effectiveness of domperidone for gastroparesis symptoms using the gastroparesis cardinal symptom index-daily diary (GCSI-DD) and to determine which symptoms improve and when with domperidone treatment. METHODS: Symptomatic patients with diabetic or idiopathic gastroparesis were enrolled. Gastric emptying was performed using 4 hour scintigraphy. GCSI-DD recorded symptoms at baseline and during six weeks of treatment with domperidone 10 mg TID. GCSI-DD records severity of nausea, early satiety, postprandial fullness, upper abdominal pain, overall gastroparesis symptoms on a scale of 0 (no symptom) to 4 (very severe) and records the number of vomiting episodes per day. RESULTS: Thirty-four patients with gastroparesis (5 diabetic, 29 idiopathic) participated in this open label study. Treatment duration averaged 36.9 ± 7.6 days. Improvement in overall gastroparesis symptoms occurred on day 3 of treatment and maintained during the treatment. Early satiety, postprandial fullness, and overall symptom severity significantly improved from baseline to the final week of treatment (P < .05 for all), whereas nausea had borderline improvement (P = .055). Side effects included palpitations (5 patients), headache (5), breast tenderness (2), menstrual bleeding (2), dizziness (1), drowsiness (1), chest pain (1), swelling (1), constipation (1). CONCLUSIONS: Domperidone improves symptoms of gastroparesis, reducing overall gastroparesis symptom severity and decreasing early satiety, postprandial fullness, and nausea. GCSI-DD is useful to document efficacy of therapy for gastroparesis.

Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis.

BACKGROUND: Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. METHODS: A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. KEY RESULTS: Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). CONCLUSIONS & INFERENCES: Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.

Gastroesophageal reflux disease-related symptom recurrence in patients discontinuing proton pump inhibitors for Bravo® wireless esophageal pH monitoring study. / Recurrencia sintomática relacionada con la enfermedad por reflujo gastroesofágico en pacientes que descontinúan los inhibidores de la bomba de protones durante el estudio inalámbrico de monitorización de pH esofágico Bravo®.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) are treated with proton pump inhibitors (PPIs). Those that do not achieve symptom relief, or non-responders, usually undergo esophageal pH monitoring off PPIs in order to confirm the presence of GERD. AIMS: To assess the efficacy of the reverse-PPI trial in evaluating the presence of GERD or its recurrence rates, as well as to identify a correlation between the symptom recurrence rates and GERD severity determined by 48-hour Bravo® esophageal pH-monitor testing. METHODS: A final total of 205 patients that underwent the 48-hour Bravo® esophageal pH-monitoring study were retrospectively included. Patients discontinued PPI usage for at least 7 days prior to testing, and completed symptom questionnaires during the 2-day test. The Bravo® test was considered positive if the percentage of time with esophageal pH <4 was >4.4%. RESULTS: A total of 363 patients underwent 48-hour Bravo® testing and of those patients, 205 were eligible for the study. Ninety-two patients reported symptoms as being «same/better¼ and 113 as being «worse¼ after stopping PPIs. Of the 92 patients with improved symptoms, 44 (48%) had documented acid reflux during the Bravo® study, compared with 65 of 113 (58%) patients with worsening symptoms that also complained of acid reflux. Of the 109 patients found to have confirmed GERD upon pH monitoring, 65 (59.6%) reported a worsening of symptoms, compared with 48 of 96 (50.0%) patients without GERD (p=0.043). Main symptoms stated to be worse included heartburn, chest pain, regurgitation, nausea, and belching (p<0.05). Of the 205 patients, 103 were off PPIs for 7 days. Seventy-two of them (68.9%) reported a worsening of symptoms, compared with 40 of the 102 (41.2%) patients that were off PPIs for>7 days (p=0.042) CONCLUSION: Symptom exacerbation following PPI cessation for at least 7 days correlated with acid reflux severity assessed by Bravo® testing. Patients off PPIs for 7 days had a higher likelihood of experiencing worsening symptoms, compared with those off PPIs for more than 7 days. These findings suggest that when PPIs are held for 7 days or less prior to Bravo® testing, acute worsening of upper GI symptoms due to the abrupt discontinuation of therapy may influence the Bravo® results. The etiology of this may be related to rebound acid hypersecretion and needs to be further elucidated in future studies.

Gastric neuromuscular histology in patients with refractory gastroparesis: Relationships to etiology, gastric emptying, and response to gastric electric stimulation.

BACKGROUND: The aims of this study were to describe the histology in gastroparesis, specifically to relate histopathology to etiology of gastroparesis (idiopathic and diabetic gastroparesis), gastric emptying, and clinical response to gastric electric stimulation. METHODS: Full thickness gastric body sections obtained during insertion of gastric stimulator in gastroparetics were stained with Hematoxylin & Eosin, Masson Trichrome and immunohistochemical stains for Neuron-Specific Enolase and c-Kit. KEY RESULTS: In all, 145 gastroparetics (71 diabetics, 71 idiopathic, 2 post-surgical, and 1 chronic intestinal pseudo-obstruction) had full thickness gastric body biopsies. A lymphocytic infiltrate was seen in the intermyenteric plexus in 22 diabetic and 23 idiopathic gastroparesis patients. Fibrosis was present in the inner circular layer in 13 diabetic and 15 idiopathics and in the outer longitudinal layer in 46 diabetic and 51 idiopathics. Diabetic gastroparesis had less ganglion cells (3.27±1.82 vs 4.81±2.81/hpf; P<.01) and less ganglia (0.90±0.44 vs 1.10±0.50/hpf; P=.01) than idiopathic gastroparesis. Interstitial cells of Cajal (ICC) count was slightly lower in the inner circular layer in diabetic than idiopathics (2.77±1.47 vs 3.18±1.34/hpf; P=.08). Delayed gastric emptying was associated with reduced ICCs in the myenteric plexus. Global therapeutic response to gastric electric stimulation was inversely related to ganglia/hpf (R=-.22; P=.008). In diabetics, improvements in nausea, vomiting, and abdominal pain were inversely related to fibrosis. CONCLUSION AND INFERENCES: Histologic assessment of full thickness gastric biopsy specimens allows correlation of histopathology to the gastroparesis disease process, its etiology, gastric emptying, and response to gastric electric stimulation treatment.

Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum.

BACKGROUND: Animal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of human gastroparesis is unclear. Our aim was to determine changes in macrophages and other cell types in the gastric antrum muscularis propria of patients with diabetic and idiopathic gastroparesis. METHODS: Full thickness gastric antrum biopsies were obtained from patients enrolled in the Gastroparesis Clinical Research Consortium (11 diabetic, 6 idiopathic) and 5 controls. Immunolabeling and quantitative assessment was done for interstitial cells of Cajal (ICC) (Kit), enteric nerves protein gene product 9.5, neuronal nitric oxide synthase, vasoactive intestinal peptide, substance P, tyrosine hydroxylase), overall immune cells (CD45) and anti-inflammatory macrophages (CD206). Gastric emptying was assessed using nuclear medicine scintigraphy and symptom severity using the Gastroparesis Cardinal Symptom Index. RESULTS: Both diabetic and idiopathic gastroparesis patients showed loss of ICC as compared to controls (Mean [standard error of mean]/hpf: diabetic, 2.28 [0.16]; idiopathic, 2.53 [0.47]; controls, 6.05 [0.62]; P=.004). Overall immune cell population (CD45) was unchanged but there was a loss of anti-inflammatory macrophages (CD206) in circular muscle (diabetic, 3.87 [0.32]; idiopathic, 4.16 [0.52]; controls, 6.59 [1.09]; P=.04) and myenteric plexus (diabetic, 3.83 [0.27]; idiopathic, 3.59 [0.68]; controls, 7.46 [0.51]; P=.004). There was correlation between the number of ICC and CD206-positive cells (r=.55, P=.008). Enteric nerves (PGP9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04). CONCLUSION: Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.

Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing.

BACKGROUND: Early satiety (ES) and postprandial fullness (PPF) are often present in gastroparesis, but the importance of these symptoms in gastroparesis has not been well-described. The aims were: (i) Characterize ES and PPF in patients with gastroparesis. (ii) Assess relationships of ES and PPF with etiology of gastroparesis, quality of life, body weight, gastric emptying, and water load testing. METHODS: Gastroparetic patients filled out questionnaires assessing symptoms (PAGI-SYM) and quality of life (PAGI-QOL, SF-36v2). Patients underwent gastric emptying scintigraphy and water load testing. KEY RESULTS: 198 patients with gastroparesis (134 IG, 64 DG) were evaluated. Early satiety was severe or very severe in 50% of patients. Postprandial fullness was severe or very severe in 60% of patients. Severity scores for ES and PPF were similar between idiopathic and diabetic gastroparesis. Increasing severity of ES and PPF were associated with other gastroparesis symptoms including nausea/vomiting, satiety/early fullness, bloating, and upper abdominal pain and GERD subscores. Increasing severity of ES and PPF were associated with increasing gastroparesis severity, decreased BMI, decreased quality of life from PAGI-QOL and SF-36 physical health. Increasing severity of ES and PPF were associated with increasing gastric retention of a solid meal and decreased volume during water load test. CONCLUSIONS & INFERENCES: Early satiety and PPF are commonly severe symptoms in both diabetic and idiopathic gastroparesis. Early satiety and PPF severity are associated with other gastroparesis symptom severities, body weight, quality of life, gastric emptying, and water load testing. Thus, ES and PPF are important symptoms characterizing gastroparesis. ClinicalTrials.gov number: NCT NCT01696747.

Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis.

BACKGROUND: Nausea and vomiting are classic symptoms of gastroparesis. It remains unclear if characteristics of nausea and vomiting are similar in different etiologies of gastroparesis. The aims of this article were as follows: to describe characteristics of nausea and vomiting in patients with gastroparesis and to determine if there are differences in nausea and vomiting in diabetic (DG) and idiopathic gastroparesis (IG). METHODS: Gastroparetic patients enrolling in the NIDDK Gastroparesis Registry underwent assessment with history and questionnaires assessing symptoms, quality of life, and a questionnaire characterizing nausea and vomiting. KEY RESULTS: Of 159 gastroparesis patients (107 IG, 52 DG), 96% experienced nausea, whereas 65% experienced vomiting. Nausea was predominant symptom in 28% and vomiting was predominant in 4%. Nausea was severe or very severe in 41%. PAGI-SYM nausea/vomiting subscore was greater with increased vomiting severity, but not nausea severity in DG than IG. Nausea was related to meals in 71%; lasting most of the day in 41%. Increasing nausea severity was related to decreased quality of life. Nausea often preceded vomiting in 82% of patients and vomiting often relieved nausea in 30%. Vomiting was more common in DG (81%) compared to IG (57%; p = 0.004). Diabetic patients more often had vomiting in the morning before eating, during the night, and when not eating. CONCLUSIONS & INFERENCES: Nausea is present in essentially all patients with gastroparesis irrespective of cause and associated with decreased quality of life. In contrast, vomiting was more prevalent, more severe, and occurred more often in DG than IG. Thus, characteristics of vomiting differ in IG vs DG.

Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes.

BACKGROUND: In studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients. METHODS: Questionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow-up differences between diabetes subtypes. KEY RESULTS: At baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p ≤ 0.05). On follow-up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life. CONCLUSIONS & INFERENCES: Baseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.

Drug-drug interactions in pharmacologic management of gastroparesis.

BACKGROUND: Gastroparesis is a disorder characterized by delayed gastric emptying due to chronic abnormal gastric motility. The treatment of the disease often entails the co-administration of several classes of pharmacological agents. These agents may be metabolized via the same pathway. Inhibition or induction of a shared metabolic pathway leads to change in the systemic levels of prescribed drugs, possibly leading to undesired clinical outcomes. PURPOSE: This review discusses different pharmacological treatment for gastroparesis patients and describes the potential for drug-drug interactions (DDIs) in some of the combinations that are currently used. Prokinetic agents such as metoclopramide and domperidone are the cornerstone in treatment of gastroparesis. Antiemetic agents such as promethazine and ondansetron are frequently administered to gastroparesis patients to reduce nausea and vomiting. Gastroparesis is prevalent in diabetic patients and therefore antidiabetic agents are also prescribed. Many of these co-administered drugs are metabolized via common drug metabolizing enzymes and this can trigger potential DDIs. The scientific literature was reviewed from the years 1975-2014 for original research articles and reviews that evaluated DDIs in gastroparesis. Many commonly prescribed combinations were predicted to cause potential DDIs in gastroparesis patients. This review will help inform about potential hazardous combinations. This information will hopefully lead to less adverse effects and more successful gastroparesis management.

Assessing pyloric sphincter pathophysiology using EndoFLIP in patients with gastroparesis.

BACKGROUND: Pyloric dysfunction has been associated with gastroparesis, particularly diabetic gastroparesis. Endoscopic functional luminal imaging probe (EndoFLIP) uses 16 sensors inside a balloon that is inflated inside a sphincter to assess physiologic characteristics. The aim of this study was to measure the pressure, diameter, cross-sectional area (CSA), and distensibility of the pylorus using EndoFLIP in patients with gastroparesis. In addition, the relationship between pyloric pathophysiology with gastroparesis etiology, symptoms, and gastric emptying was assessed. METHODS: EndoFLIP was performed in 54 patients (39 idiopathic gastroparesis, 15 diabetic gastroparesis). The EndoFLIP catheter was passed endoscopically so that the balloon straddled the pylorus. Pressure, diameter, CSA, and distensibility of the pylorus were measured at 20, 30, 40, and 50 cc balloon volume. KEY RESULTS: Pyloric sphincter contour was seen best at 40 cc balloon distension (diameter 12.2 ± 0.44 mm, CSA 125.2 ± 9.15 mm(2), pressure 18.0 ± 1.23 mmHg, length 1.59 ± 0.34 cm, distensibility 10.7 ± 2.57 mm(2)/mmHg). There was a wide range seen in diameter (5.6-22.1 mm) and distensibility (1-55 mm(2)/mmHg) of the pylorus. Symptoms of early satiety and postprandial fullness were inversely correlated with pyloric sphincter diameter and CSA. No significant difference was seen between diabetic and idiopathic gastroparetics. CONCLUSIONS & INFERENCES: EndoFLIP is a novel technique that can be used to assess pyloric physiologic characteristics. Early satiety and postprandial fullness were inversely correlated with diameter and CSA of the pyloric sphincter. No significant differences were seen comparing diabetic and idiopathic gastroparetics. This technology may be of benefit to help select patients with pyloric sphincter abnormalities.

Effect of dietary fat and food consistency on gastroparesis symptoms in patients with gastroparesis.

BACKGROUND: Nutrition therapy for gastroparesis focuses on reducing meal size, fiber, fat intake, and increasing liquids intake relative to solid foods. Evidence to support these dietary interventions has been anecdotal. The aim of this study was to determine the effect of fat intake and solid/liquid meal consistency on symptoms in gastroparesis. METHODS: Twelve patients with gastroparesis were studied on four separate days receiving one of four meals each day in a randomized order: high-fat solid, high-fat liquid, low-fat liquid, and low-fat solid meal. At each visit, eight gastrointestinal symptoms were rated from 0 (none) to 4 (very severe) every 15 min, before and for 4 h after meal ingestion. KEY RESULTS: There was an increase in the total symptom score in the following order: high-fat solid > low-fat solid > high-fat liquid > low-fat liquid. For the high-fat solid meal, symptoms remained elevated throughout the 4 h postprandial period. Severity of nausea more than doubled after the high-fat solid meal, whereas the low-fat liquid meal caused the least increase in nausea. CONCLUSIONS & INFERENCES: A high-fat solid meal significantly increased overall symptoms among individuals with gastroparesis, whereas a low-fat liquid meal had the least effect. With respect to nausea, low-fat meals were better tolerated than high-fat meals, and liquid meals were better tolerated than solid meals. These data provide support for recommendations that low-fat and increased liquid content meals are best tolerated in patients with symptomatic gastroparesis.

Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis.

BACKGROUND: There is increasing evidence for specific cellular changes in the stomach of patients with diabetic (DG) and idiopathic (IG) gastroparesis. The most significant findings are loss of interstitial cells of Cajal (ICC), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD206+ and iNOS+ cells. To investigate associations between cellular phenotypes and ICC. METHODS: Full thickness gastric body biopsies were obtained from non-diabetic controls (C), diabetic controls (DC), DG, and IG patients. Sections were labeled for CD45, CD206, Kit, iNOS, and putative human macrophage markers (HAM56, CD68, and EMR1). Immunoreactive cells were quantified from the circular muscle layer. KEY RESULTS: Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between iNOS+ cells and ICC in the DC group, but not the other groups. CD68 and HAM56 reliably labeled the same cell populations, but EMR1 labeled other cell types. CONCLUSIONS & INFERENCES: Depletion of ICC and correlation with changes in CD206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages.

Bolus retention in hiatal hernia identified by high-resolution esophageal manometry with impedance.

BACKGROUND: Esophageal acid retention in a hiatal hernia (HH) may play a role in gastro-esophageal reflux. The aims of this study were to determine the prevalence of bolus retention (BR) in HH and to compare pressure profiles in patients with HH with BR in the hernia to those with bolus clearance (BC) through the hernia using high-resolution esophageal manometry with impedance (HREMI). METHODS: Clinical HREMI studies with HH ≥1.5 cm were analyzed for lower esophageal sphincter (LES) and crural diaphragm (CD) pressures and pressure profiles during 12 saline swallows. Impedance was analyzed for swallow retention in the HH. KEY RESULTS: Bolus retention in a HH was present in 35 of 53 (66%) patients with a HH. Patients with BR had overall lower pressure profiles including a lower basal LES pressure (14.8 ± 10.6 vs 28.9 ± 16.8 mmHg; p = 0.0001), LES-CD gradient (6.8 ± 17.9 vs 20.6 ± 12.2 mmHg; p = 0.002), residual LES pressure (2.5 ± 4.6 vs 6.1 ± 12.2 mmHg; p = 0.017), amplitude of distal esophageal contractions (83.2 ± 38.8 vs 111.2 ± 42.8 mmHg; p = 0.020), and distal contractile integral (1487 ± 1016 vs 2608 ± 1221 mmHg-cm-sec; p = 0.001) compared to the BC group. Patients with BR were more likely to have a larger sized HH compared to the BC group (3.1 ± 1.6 vs 2.1 ± 0.6 cm; p = 0.016); similar pressure changes were found when the groups were divided up by HH sizes. CONCLUSIONS & INFERENCES: Bolus retention was seen in 66% of patients with HH. Bolus retention in the HH was associated with larger HH size, lower LES pressure, and lower esophageal contractile pressures compared to those with BC.

Metoclopramide nasal spray is effective in symptoms of gastroparesis in diabetics compared to conventional oral tablet.

BACKGROUND: Delayed gastric emptying symptoms interfere with the absorption of oral medications. Intranasal metoclopramide is being developed as an alternative to oral metoclopramide for patients with diabetic gastroparesis. METHODS: To compare the efficacy and safety of metoclopramide nasal spray to oral tablets in diabetic patients with symptoms of gastroparesis, this randomized, open-label, parallel design study randomized subjects to 10 or 20 mg nasal spray or 10 mg tablet four times a day for 6 weeks. Efficacy was evaluated using a total symptom score (TSS). KEY RESULTS: Eighty-nine subjects were enrolled. For the intention to treat population, both nasal dose groups (10 and 20 mg) had lower TSS with treatment compared to the oral 10 mg group. The change from baseline in TSS for nasal 20 mg was greater than the oral 10 mg at Week 6 (p = 0.026). For the per-protocol population, there was a significant difference in the TSS between baseline and Week 6 for both the nasal 10 mg (p = 0.026) and the nasal 20 mg (p = 0.008) cohorts compared to the oral 10 mg group. Based on the definition of a responder, 88.9% of subjects who received oral 10 mg, 91.2% who received nasal 10 mg, and 97.1% who received nasal 20 metoclopramide were classified as responders. The side-effect profile of the metoclopramide nasal spray was favorable. More side effects, especially nausea, occurred with the oral tablets. CONCLUSIONS & INFERENCES: Metoclopramide nasal spray offers better symptom control than metoclopramide oral tablet in diabetic patients with symptoms of gastroparesis.

Bodyweight in patients with idiopathic gastroparesis: roles of symptoms, caloric intake, physical activity, and body metabolism.

BACKGROUND: Most gastroparetic patients are underweight probably because of frequently experienced early satiety, nausea, and vomiting. Some gastroparesis (GP) patients, however, are overweight, for reasons that are not well understood. The aim of this study was to evaluate the factors that influence bodyweight such as resting energy and exercise-related expenditure, symptoms of early satiety, nausea and vomiting, and caloric intake in patients with idiopathic GP and in healthy controls. METHODS: Thirty-nine healthy controls and 29 subjects with idiopathic GP were studied. Resting energy expenditure (indirect calorimetry), body composition (bioelectrical impedance), dietary intake (Block Food Frequency Questionnaire), symptoms (Patient Assessment of Upper GI Symptoms), and physical activity (Paffenbarger exercise survey) were assessed. KEY RESULTS: Both median caloric intake (1242 vs 1804 kcal; p = 0.005) and caloric expenditure (486 vs 2172 kcal; p < 0.01) were significantly lower in patients with GP as compared to controls although BMI (25.8 ± 5.8 vs 24.3 ± 4.0 kg/m²) and resting energy expenditure (1327 ± 293 vs 1422 ± 243 kcal) were similar. On the other hand, the 12 GP patients who had gained weight (GW) since diagnosis had lower symptom severity (12.9 ± 4.4 vs 19.3 ± 6.3; p < 0.05), consumed more calories (1342 vs 1134 kcal; p = 0.08) and expended less calories for activity per week (406 vs 644 median kcal; p = 0.45) compared to the 17 GP patients who had lost weight or remained weight neutral (LW). CONCLUSIONS & INFERENCES: Patients with GP, although in energy balance, consumed and expended less calories than healthy controls. A subgroup of patients with GP who were less symptomatic, gained weight because of increased caloric intake and reduced energy expenditure.

Gastric electrical stimulation with Enterra therapy improves symptoms of idiopathic gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) is a therapeutic option for intractable symptoms of gastroparesis (GP). Idiopathic GP (ID-GP) represents a subset of GP. AIMS: A prospective, multicenter, double-blinded, randomized, crossover study to evaluate the safety and efficacy of Enterra GES in the treatment of chronic vomiting in ID-GP. METHODS: Thirty-two ID-GP subjects (mean age 39; 81% F, mean 7.7 years of GP) were implanted with GES. The stimulator was turned ON for 1½ months followed by double-blind randomization to consecutive 3-month crossover periods with the device either ON or OFF. ON stimulation was followed in unblinded fashion for another 4.5 months. Twenty-five subjects completed the crossover phase and 21 finished 1 year of follow-up. KEY RESULTS: During the unblinded ON period, there was a reduction in weekly vomiting frequency (WVF) from baseline (61.2%, P < 0.001). There was a non-significant reduction in WVF between ON vs OFF periods (the primary outcome) with median reduction of 17% (P > 0.10). Seventy-five percent of patients preferred the ON vs OFF period (P = 0.021). At 1 year, WVF remained decreased (median reduction = 87%, P < 0.001), accompanied by improvements in GP symptoms, gastric emptying and days of hospitalization (P < 0.05). CONCLUSIONS & INFERENCES: (i) In this prospective study of Enterra GES for ID-GP, there was a reduction in vomiting during the initial ON period; (ii) The double-blind 3-month periods showed a non-significant reduction in vomiting in the ON vs OFF period, the primary outcome variable; (iii) At 12 months with ON stimulation, there was a sustained decrease in vomiting and days of hospitalizations.

Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting.

BACKGROUND: Factors associated with abdominal pain in gastroparesis are incompletely evaluated and comparisons of pain vs other symptoms are limited. This study related pain to clinical factors in gastroparesis and contrasted pain/discomfort- with nausea/vomiting-predominant disease. METHODS: Clinical and scintigraphy data were compared in 393 patients from seven centers of the NIDDK Gastroparesis Clinical Research Consortium with moderate-severe (Patient Assessment of Upper Gastrointestinal Disorders Symptoms [PAGI-SYM] score ≥ 3) vs none-mild (PAGI-SYM < 3) upper abdominal pain and predominant pain/discomfort vs nausea/vomiting. KEY RESULTS: Upper abdominal pain was moderate-severe in 261 (66%). Pain/discomfort was predominant in 81 (21%); nausea/vomiting was predominant in 172 (44%). Moderate-severe pain was more prevalent with idiopathic gastroparesis and with lack of infectious prodrome (P ≤ 0.05) and correlated with scores for nausea/vomiting, bloating, lower abdominal pain/discomfort, bowel disturbances, and opiate and antiemetic use (P < 0.05), but not gastric emptying or diabetic neuropathy or control. Gastroparesis severity, quality of life, and depression and anxiety were worse with moderate-severe pain (P ≤ 0.008). Factors associated with moderate-severe pain were similar in diabetic and idiopathic gastroparesis. Compared to predominant nausea/vomiting, predominant pain/discomfort was associated with impaired quality of life, greater opiate, and less antiemetic use (P < 0.01), but similar severity and gastric retention. CONCLUSIONS & INFERENCES: Moderate-severe abdominal pain is prevalent in gastroparesis, impairs quality of life, and is associated with idiopathic etiology, lack of infectious prodrome, and opiate use. Pain is predominant in one fifth of gastroparetics. Predominant pain has at least as great an impact on disease severity and quality of life as predominant nausea/vomiting.

Symptoms and esophageal motility based on phenotypic findings of scleroderma.

Scleroderma esophagus is characterized by ineffective peristalsis and reduced esophageal sphincter pressure. Esophageal disease in scleroderma can precede cutaneous manifestations and has been associated with Raynaud's phenomenon (RP) and pulmonary fibrosis (PF). The objective of the study is to evaluate the impact of cutaneous findings, RP, and PF on demographics, symptoms, and esophageal motility in patients with scleroderma. Scleroderma patients with esophageal involvement were included after review of esophageal manometries and charts over a 6-year period. High-resolution esophageal manometry was performed. Patients completed a symptom questionnaire. The study enrolled 28 patients (22 females; mean age 50.3 ± 12.8 years) with scleroderma esophagus. Patients without skin involvement (n= 12) reported more severe heartburn (P= 0.02), while those with cutaneous findings (n= 16) had more frequent dysphagia with solids (P= 0.02). Patients with RP (n= 22) had lower amplitude of distal esophageal contractions (P= 0.01) than those without RP (n= 6). Patients with PF (n= 11) reported more severe coughing and wheezing (both P= 0.03) than those without lung disease (n= 17). This study highlights subgroups of patients with scleroderma esophagus according to phenotypic findings of dermatologic changes, RP, and PF. Heartburn and dysphagia are important symptoms that may be associated with different stages of disease progression based on skin changes in scleroderma. RP was associated with greater esophageal dysmotility. Coughing and wheezing were more severe in patients with PF.

Slow esophageal propagation velocity: association with dysphagia for solids.

BACKGROUND: Spastic disorders of the esophagus, associated with rapid esophageal propagation velocity, are classically associated with dysphagia and/or chest pain. The aim of this study was to characterize patients with slow esophageal propagation velocity (SPV) on high-resolution esophageal manometry (HRM). METHODS: A review of patients undergoing HRM was conducted during 1-year study period. Patients with achalasia, aperistalsis, and diffuse esophageal spasm were excluded. Patients with contractile front velocity (CFV) ≤ 2.3 cm s(-1) were defined as having SPV, whereas normal propagation velocity (NPV) was defined as ≥ 2.6 cm s(-1). A composite isobaric contour of all swallows for each patient was generated to determine composite distal contraction latency (cDL). KEY RESULTS: A total of 650 HRMs were reviewed and 552 met inclusion criteria. 173 patients had SPV and 339 had NPV. There was a greater female predominance in the SPV group compared with NPV (75.7%vs 66.4%, P = 0.03). Patients in the SPV group reported more dysphagia for solids (66.3%vs 53.3%; P = 0.004) and nausea (68.6%vs 59.0%; P = 0.04) than NPV group. Dysphagia for solids was the only symptom significantly associated with SPV group (OR = 2.21, CI = 1.21-4.02; P = .01). There was a negative correlation between CFV and cDL, r = -0.494, P < 0.001. CONCLUSIONS & INFERENCES: Patients with SPV have a higher prevalence of dysphagia for solids and nausea when compared with NPV. Dysphagia for solids was the only symptom significantly associated with SPV group. Thus, abnormal esophageal propagation velocity (both slow and rapid) is associated with dysphagia.