Constipation in Patients With Symptoms of Gastroparesis: Analysis of Symptoms and Gastrointestinal Transit.

BACKGROUND & AIMS: Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC). METHODS: Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper GI Symptoms [PAGI-SYM] and Rome III functional GI disorder questionnaire. RESULTS: Of 338 patients with symptoms of gastroparesis, 242 (71.5%) had delayed gastric emptying by scintigraphy; 298 (88.2%) also met criteria for functional dyspepsia. Severity of constipation was severe/very severe in 34% patients, moderate in 24%, and none/very mild/mild in 42%. Increasing severity of constipation was associated with increasing symptoms of gastroparesis and presence of irritable bowel syndrome (IBS). Severity of constipation was not associated with gastric retention on GES or WMC. Delayed colonic transit was present in 108 patients (32% of patients). Increasing severity of constipation was associated with increasing small bowel transit time, colonic transit time, and whole gut transit time. CONCLUSIONS: Severe/very severe constipation and delayed colon transit occurs in a third of patients with symptoms of gastroparesis. The severity of constipation is associated with severity of gastroparesis symptoms, presence of IBS, small bowel and colon transit delay, but not delay in gastric emptying. ClinicalTrials.gov Identifier: NCT01696747.

Role of Cannabis and Its Derivatives in Gastrointestinal and Hepatic Disease.

Medical and recreational cannabis use has increased dramatically over the last decade, resulting from mainstream cultural acceptance and legalization in several countries worldwide. Cannabis and its derivatives affect many gastrointestinal processes via the endocannabinoid system (ECS). The ECS influences gastrointestinal homeostasis through anti-inflammatory, anti-nociceptive, and anti-secretory effects. Some gastrointestinal disorders might therefore be treated with cannabinoids. Despite numerous studies in cell lines and animals, few human studies have evaluated the therapeutic effects of cannabinoids. Cannabis' schedule 1 drug status has limited its availability in research; cannabis has been legalized only recently, in some states, for medicinal and/or recreational use. Cannabinoids can alleviate chemotherapy-induced nausea and emesis and chronic pain. Studies have demonstrated the important roles of the ECS in metabolism, obesity, and nonalcoholic fatty liver disease and the anti-inflammatory effects of cannabis have been investigated in patients with inflammatory bowel diseases. Despite its potential benefits, undesired or even detrimental effects of cannabis can limit its use. Side effects such as cannabinoid hyperemesis syndrome affect some users. We review the ECS and the effects of cannabis and its derivatives on gastrointestinal and hepatic function in health and disease.

Impact of patient position on esophageal motility disorders using high-resolution esophageal manometry with impedance (HREMI): supine versus upright swallows.

BACKGROUND: High-resolution esophageal manometry with impedance (HREMI) performed with supine patient positioning is used to evaluate patients for esophageal dysmotility. However, most patients experience symptoms related to esophageal dysmotility when eating or drinking upright. The aims of this study are to: (1) compare HREMI metrics in supine versus upright position; and (2) determine if upright position alters motility characterization of patients. METHODS: HREMI of twelve wet swallows in supine position and five wet swallows in upright position were performed on normal subjects (NS) and consecutive patients. Chicago Classification v3.0 (CC) diagnoses were evaluated in the supine position and a modified version of the Chicago Classification system was used in the upright position using normative upright values for DCI and IRP. RESULTS: DCI decreased in NS by 414 mmHg × cm × sec (p = 0.001) and patients by 613 mmHg × cm × sec (p < 0.001). IRP decreased in NS by 6.2 mmHg (p < 0.001) and patients by 4.6 mmHg (p < 0.001). The rate of successful bolus clearance decreased in the upright position in patients by 11% (p < 0.001), but no statistically significant differences were observed in NS. 82 of 200 patients (41%) had a change in CC diagnosis in the upright position. Bolus clearance in the upright position varied in patients depending on their diagnosis in the upright position. CONCLUSIONS: Upright swallows had lower LES, IRP, DCI and UES pressures in both normal subjects and patients with decreased bolus clearance in patients. Upright positioning can alter esophageal motility patterns and enhance diagnostic yield. Thus, upright swallows supplement supine swallows to help characterize esophageal dysmotility.

Botulinum Toxin A Improves Symptoms of Gastroparesis.

BACKGROUND AND AIMS: Pyloric injections of botulinum toxin A (BoNT/A) have shown benefit in open-label studies for patients with gastroparesis but not in randomized trials. We sought to examine the effectiveness of BoNT/A injections in a prospective open-label trial of patients with gastroparesis to assess specific symptom improvements over the course of 6 months. We also wanted to determine if specific biochemical measures including creatinine kinase, lactate dehydrogenase, aldolase, and C-reactive protein suggesting muscular injection could be used to predict successful response to pyloric injections of BoNT/A. METHODS: Patients with gastroparesis undergoing pyloric BoNT/A injections for the treatment of symptomatic gastroparesis were enrolled. The patients completed the Gastroparesis Cardinal Symptom Index (GCSI) at the initial encounter and at 1, 3, and 6 months. Blood samples were collected before and 1 h after BoNT/A therapy. RESULTS: We enrolled 34 patients for serum analysis of which 25 patients were available for symptom follow-up. Sixty-four percent of patients had an improvement in symptoms at 1 month. Patients with improved GCSI total score at 1 month had an improvement in most individual symptoms evaluated. For patients that improved at 1 month, this improvement often extended up to 6 months (p = 0.04). Serum measures studied did not correlate with clinical outcomes. CONCLUSIONS: BoNT/A therapy to the pylorus provided symptomatic improvement at 1 month in 64% of patients. For those patients initially responding, the improvement can last out to 6 months. The biochemical markers did not serve to predict the outcome of injections.

Marijuana Use in Patients with Symptoms of Gastroparesis: Prevalence, Patient Characteristics, and Perceived Benefit.

BACKGROUND: Marijuana may be used by some patients with gastroparesis (Gp) for its potential antiemetic, orexigenic, and pain-relieving effects. AIMS: The aim of this study was to describe the use of marijuana by patients for symptoms of Gp, assessing prevalence of use, patient characteristics, and patients' perceived benefit on their symptoms of Gp. METHODS: Patients with symptoms of Gp underwent history and physical examination, gastric emptying scintigraphy, and questionnaires assessing symptoms. Patients were asked about the current use of medications and alternative medications including marijuana. RESULTS: Fifty-nine of 506 (11.7%) patients with symptoms of Gp reported current marijuana use, being similar among patients with delayed and normal gastric emptying and similar in idiopathic and diabetic patients. Patients using marijuana were younger, more often current tobacco smokers, less likely to be a college graduate, married or have income > $50,000. Patients using marijuana had higher nausea/vomiting subscore (2.7 vs 2.1; p = 0.002), higher upper abdominal pain subscore (3.5 vs 2.9; p = 0.003), more likely to be using promethazine (37 vs 25%; p = 0.05) and dronabinol (17 vs 3%; p < 0.0001). Of patients using marijuana, 51% had been using it for more than 2 years, 47% were using this once or more per day, and 81% of marijuana users rated their benefit from marijuana as better or much better. CONCLUSIONS: A subset of patients (12%) with symptoms of Gp use marijuana. Patients with severe nausea and abdominal pain were more likely to use marijuana and perceive it to be beneficial for their symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01696747.

Vascular pressure bands on high-resolution esophageal manometry with impedance studies.

Horizontal pressure bands on high-resolution esophageal manometry with impedance (HREMI) tracings are often seen and thought to be due to cardiovascular structures compressing the esophagus. The aim of this study was to determine the prevalence and location of vascular pressure bands on HREMI studies and correlate these pressure bands to bolus clearance. HREMI studies in supine and upright positions from patients and normal volunteers were reviewed. Pressure bands were defined as bands of horizontal pressure greater than the 20 mmHg isobaric contour. Each swallow was reviewed with impedance to determine if bolus transit was impaired by the band. 38.6% of 251 patients and 36.4% of 11 normal controls had a pressure band present. There were a greater number of bands in supine versus upright position (patients: 130 vs. 25, P < 0.001 and controls: 6 vs. 1). Patients with pressure bands had similar demographics (age, gender, BMI) compared to those without. Average distal contractile integral of bands was greater in supine compared to upright (133 ± 201 vs. 60 ± 148 mmHg cm s, P < 0.05). Bands were commonly located clustered at 46 and 72% of esophageal length. Bolus transit was impaired by bands in 20.4% of supine and 14.0% of upright swallows. Vascular pressure bands can have a prominent appearance on HREMI studies, present in, being more prevalent and having greater pressure in the supine than the upright position. These vascular bands, when present, may impair esophageal transit.

Eluxadoline for Irritable Bowel Syndrome with Diarrhea.

Background Effective and safe treatments are needed for patients who have irritable bowel syndrome (IBS) with diarrhea. We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline, a new oral agent with mixed opioid effects (µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist), in patients with IBS with diarrhea. Methods We randomly assigned 2427 adults who had IBS with diarrhea to eluxadoline (at a dose of 75 mg or 100 mg) or placebo twice daily for 26 weeks (IBS-3002 trial) or 52 weeks (IBS-3001 trial). The primary end point was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days from weeks 1 through 12 and from weeks 1 through 26. Results For weeks 1 through 12, more patients in the eluxadoline groups (75 mg and 100 mg) than in the placebo group reached the primary end point (IBS-3001 trial, 23.9% with the 75-mg dose and 25.1% with the 100-mg dose vs. 17.1% with placebo; P=0.01 and P=0.004, respectively; IBS-3002 trial, 28.9% and 29.6%, respectively, vs. 16.2%; P<0.001 for both comparisons). For weeks 1 through 26, the corresponding rates in IBS-3001 were 23.4% and 29.3% versus 19.0% (P=0.11 and P<0.001, respectively), and the corresponding rates in IBS-3002 were 30.4% and 32.7% versus 20.2% (P=0.001 and P<0.001, respectively). The most common adverse events associated with 75 mg of eluxadoline and 100 mg of eluxadoline, as compared with placebo, were nausea (8.1% and 7.5% vs. 5.1%), constipation (7.4% and 8.6% vs. 2.5%), and abdominal pain (5.8% and 7.2% vs. 4.1%). Pancreatitis developed in 5 (2 in the 75-mg group and 3 in the 100-mg group) of the 1666 patients in the safety population (0.3%). Conclusions Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea in men and women, with sustained efficacy over 6 months in patients who received the 100-mg dose twice daily. (Funded by Furiex Pharmaceuticals, an affiliate of Allergan; IBS-3001 and IBS-3002 ClinicalTrials.gov numbers, NCT01553591 and NCT01553747 , respectively.).

Ethnic, Racial, and Sex Differences in Etiology, Symptoms, Treatment, and Symptom Outcomes of Patients With Gastroparesis.

BACKGROUND & AIMS: Gastroparesis is a chronic disorder of the stomach characterized by nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. There is limited information on gastroparesis in minority populations. We assessed ethnic, racial, and sex variations in the etiology, symptoms, quality of life, gastric emptying, treatments, and symptom outcomes of patients with gastroparesis. METHODS: We collected information from the National Institutes of Health Gastroparesis Consortium on 718 adult patients, from September 2007 through December 2017. Patients were followed every 4 or 6 months, when data were collected on medical histories, symptoms (based on answers to the PAGI-SYM questionnaires), and quality of life (based on SF-36). Follow-up information collected at 1 year (48 week) was used in this analysis. Comparisons were made between patients of self-reported non-Hispanic white, non-Hispanic black, and Hispanic ethnicities, as well as and between male and female patients. RESULTS: Our final analysis included 552 non-Hispanic whites (77%), 83 persons of Hispanic ethnicity (12%), 62 non-Hispanic blacks (9%), 603 women (84%), and 115 men (16%). A significantly higher proportion of non-Hispanic blacks (60%) had gastroparesis of diabetic etiology than of non-Hispanic whites (28%); non-Hispanic blacks also had more severe retching (2.5 vs 1.7 score) and vomiting (2.9 vs 1.8 score) and a higher percentage were hospitalized in the past year (66% vs 38%). A significantly higher proportion of Hispanics had gastroparesis of diabetic etiology (59%) than non-Hispanic whites (28%), but Hispanics had less-severe nausea (2.7 vs 3.3 score), less early satiety (3.0 vs 3.5 score), and a lower proportion used domperidone (8% vs 21%) or had a peripherally inserted central catheter (1% vs 7%). A higher proportion of women had gastroparesis of idiopathic etiology (69%) than men (46%); women had more severe symptoms of stomach fullness (3.6 vs 3.1 score), early satiety (3.5 vs 2.9 score), postprandial fullness (3.7 vs 3.1 score), bloating (3.3 vs 2.6 score), stomach visibly larger (3.0 vs 2.1 score), and upper abdominal pain (2.9 vs 2.4 score). A lower proportion of women were hospitalized in past year (39% vs 53% of men). CONCLUSIONS: In patients with gastroparesis, etiologies, symptom severity, and treatments vary among races and ethnicities and between sexes. ClinicalTrials.gov Identifier: NCT01696747.

Effect of Chronic Domperidone Use on QT Interval: A Large Single Center Study.

GOALS: The goal of this study was to determine the effect and safety of domperidone on QTc interval at the commonly prescribed doses of 30 to 80 mg daily. BACKGROUND: Domperidone is a dopamine receptor antagonist used for the treatment of gastroparesis. However, it has been associated with QT prolongation, ventricular arrhythmias, and sudden cardiac death. STUDY: This study analyzed patients prescribed domperidone for treatment of gastroparesis between January 2012 and September 2017 at a single center. This study reviewed EKGs, primarily the QTc interval, taken at baseline, 2 to 6 months after initiation of domperidone, 6 to 12 months after initiation, and ≥12 months after initiation. Concurrent QTc prolonging medications were recorded for each patient. The primary endpoint was QTc prolongation >500 ms. Secondary endpoints were QTc >450 ms for males, a QTc>470 ms for females, QTc prolongation ≥20 ms above baseline, and QTc prolongation >60 ms above baseline. RESULTS: In total, 246 patients were included for analysis (age, 46.3±17.4 y; F 209). EKGs were available for all 246 patients before treatment, 170 patients at 2 to 6 months, 135 at 6 to 12 months, and 152 patients at least 1 year after domperidone initiation.Of 246 subjects, 15 patients (6.1%, 9 female) had clinically important QTc prolongation; 11 had QTc >450 ms for males or >470 ms for females; none had QTc prolongation >500 ms; 5 (2.0%) had >60 ms over baseline and 61 (24.7%) patients had QTc increase of ≥20 ms but <60 ms from baseline. CONCLUSIONS: Domperidone at the conventionally used doses to treat gastroparesis (30 to 80 mg/d) was associated with QTc prolongation in only 6% of patients with no QT interval reaching the point considered to be clinically significant. These data suggest that domperidone can be safely prescribed at doses of 30 to 80 mg daily for the treatment of gastroparesis.

Multiple Rapid Swallows (MRS) Complements Single-Swallow (SS) Analysis for High-Resolution Esophageal Manometry (HREM).

BACKGROUND: Multiple rapid swallows (MRS) during HREM assess post-deglutitive inhibition, LES relaxation, and subsequent esophageal contraction. AIMS: (1) To determine the relationship between MRS and single-swallow (SS) responses and (2) to determine if MRS provides information for symptomatic patients. METHODS: Healthy volunteers (HVs) and patients underwent HREM [30-s landmark, ten 5-mL SS, MRS (5 consecutive 2-mL swallows every 2-3 s)] and were analyzed with ManoView software version 3 with CC version 3.0. RESULTS: In 20 HVs, MRS response consisted of: (1) reduction in GEJ pressure; (2) absence of esophageal contractile activity during MRS; and (3) post-MRS peristaltic contraction greater than SS contractions. In 20 HVs and 403 patients, MRS IRP correlated with SS IRP (r = 0.65; p < 0.0001) and post-MRS contraction DCI correlated with SS DCI (r = 0.76; p < 0.0001). Abnormally elevated MRS IRP was seen in 68% type 2 achalasia, 50% type 3 achalasia, 47% EGJOO, and 9% jackhammer. Increased MRS DCI was seen in 53% type 2 achalasia, 92% type 3 achalasia, 10% EGJOO, 22% jackhammer, and 18% DES. Increased DCI post-MRS was seen in 38% patients with jackhammer, 8% type 3 achalasia, 12% EGJOO, and 9% DES. 14 out of 143 (10%) patients with normal or indeterminate results on SS analysis had at least one abnormality on MRS. CONCLUSIONS: MRS IRP correlated with SS IRP, and post-MRS DCI correlated with SS DCI. Patients with defined CC disorders have abnormalities on MRS. There were MRS abnormalities in some patients with normal SS studies, most notably suggesting impaired LES relaxation and/or spastic esophageal motility. MRS may complement the baseline SS study analysis.

Abdominal Pain in Patients with Gastroparesis: Associations with Gastroparesis Symptoms, Etiology of Gastroparesis, Gastric Emptying, Somatization, and Quality of Life.

Abdominal pain can be an important symptom in some patients with gastroparesis (Gp). AIMS: (1) To describe characteristics of abdominal pain in Gp; (2) describe Gp patients reporting abdominal pain. METHODS: Patients with idiopathic gastroparesis (IG) and diabetic gastroparesis (DG) were studied with gastric emptying scintigraphy, water load test, wireless motility capsule, and questionnaires assessing symptoms [Patient Assessment of Upper GI Symptoms (PAGI-SYM) including Gastroparesis Cardinal Symptom Index (GCSI)], quality of life (PAGI-QOL, SF-36), psychological state [Beck Depression Inventory (BDI), State-Trait Anxiety Index (STAI), PHQ-15 somatization scale]. RESULTS: In total, 346 Gp patients included 212 IG and 134 DG. Ninety percentage of Gp patients reported abdominal pain (89% DG and 91% IG). Pain was primarily in upper or central midline abdomen, described as cramping or sickening. Upper abdominal pain was severe or very severe on PAGI-SYM by 116/346 (34%) patients, more often by females than by males, but similarly in IG and DG. Increased upper abdominal pain severity was associated with increased severity of the nine GCSI symptoms, depression on BDI, anxiety on STAI, somatization on PHQ-15, the use of opiate medications, decreased SF-36 physical component, and PAGI-QOL, but not related to severity of delayed gastric emptying or water load ingestion. Using logistic regression, severe/very severe upper abdominal pain associated with increased GCSI scores, opiate medication use, and PHQ-15 somatic symptom scores. CONCLUSIONS: Abdominal pain is common in patients with Gp, both IG and DG. Severe/very severe upper abdominal pain occurred in 34% of Gp patients and associated with other Gp symptoms, somatization, and opiate medication use. ClinicalTrials.gov Identifier: NCT01696747.

Outcomes of surgical intervention for refractory gastroparesis: a systematic review.

BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying with symptoms of nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. Various surgical options exist to treat GP not responding to medical treatments (refractory GP), including gastric electric stimulation (GES), gastrectomy (GTx), and pyloric interventions (PI), whereas the outcomes of these procedures have been published; few comparison studies exist. METHODS: PubMed literature review for articles from September 1988 to October 2017 was performed for prospective and retrospective analyses reporting >5 patients. Unweighted (per study) and weighted (per patient) overall improvement and improvement in symptoms of nausea, vomiting, and abdominal pain were calculated and compared for the different procedures. RESULTS: Of 325 studies satisfying search criteria, 38 met the study criteria and were included for analysis. Total response to intervention, both weighted and unweighted, was greater with PIs compared to GES (P < 0.05). For unweighted symptom improvements, nausea improved more with PI than with GES (P < 0.05). GES improved vomiting more than epigastric pain (P < 0.05). For weighted symptom improvements, pyloric surgery and GTx improved vomiting compared to GES (P < 0.05). CONCLUSIONS: Published outcomes of GES, pyloric surgery, and GTx for refractory GP are compared. Pyloromyotomy/pyloroplasty improves patient response greater than with GES. Weighing by number of studies, pyloric surgery improves nausea and abdominal pain greater than GES. For GES, vomiting is more likely to improve than abdominal pain. Weighing by number of patients, pyloric surgery and GTx improved vomiting compared to GES.

Utility of Esophageal High-Resolution Manometry in Clinical Practice: First, Do HRM.

Esophageal high-resolution manometry (HRM) has advanced the understanding of esophageal motor function and the ability to diagnose and manage disorders of esophageal motility. In this review, we describe the indications for and the technical performance of HRM. The Chicago classification of esophageal motor function, now in its third iteration, streamlines and standardizes the nomenclature and basic interpretation of HRM data depicted as Clouse topographic plots. In clinical practice, HRM is an important diagnostic test for patients with dysphagia as well as patients with suspected gastroesophageal reflux disease (GERD), particularly in those patients with a suboptimal symptomatic response to antisecretory therapy. HRM can support diagnoses such as achalasia, as well as provide evidence for behavioral disorders such as rumination syndrome or supragastric belching with the assistance of postprandial HRM with impedance. Further, the GERD classification of motor function introduces a three-part hierarchical evaluation of esophageal motor function in GERD, highlighting the value of assessment of esophageal contractile reserve through provocative maneuvers during HRM such as multiple rapid swallows.

Effect of Bifidobacterium infantis 35624 (Align) on the Lactulose Breath Test for Small Intestinal Bacterial Overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) may cause symptoms in patients with abdominal bloating, distension, and gas. SIBO can be assessed using the lactulose breath test (LBT). A commonly used probiotic supplement is Align containing Bifidobacterium infantis 35624. The aim of this study was to determine the effect of B. infantis 35624 on hydrogen and methane excretion during LBT. METHODS: Healthy subjects underwent LBT before and after 2 weeks of daily Align administration. Hydrogen and methane concentrations were measured for each breath sample. Results are expressed as mean ± SE and analyzed using repeated measures ANCOVA. A breath test was considered positive if hydrogen and/or methane increased > 20 ppm above baseline by 90 min of the test or if a dual hydrogen peak was present. RESULTS: Nineteen healthy subjects were studied. Hydrogen levels were similar pre- and post-probiotic across the 3-h study (p = 0.768). In contrast, methane levels were significantly higher with probiotic administration (p = 0.012). A rise in methane > 20 ppm was seen in three subjects pre-probiotic but six post-probiotic. Of the 19 subjects, an "abnormal" LBT pre-probiotic was present in ten subjects and during the probiotic, 13 were abnormal. CONCLUSIONS: This study found that 2 weeks of B. infantis 35624 (Align) supplementation affects LBT assessment for SIBO by significantly increasing methane, but not hydrogen, excretion after lactulose administration. Methane levels reached values that would be considered positive for SIBO patients. This study suggests that patients undergoing LBT should discontinue probiotics prior to the test as these supplements may alter the test results.

Gastric Per Oral Endoscopic Myotomy (G-POEM) for the Treatment of Refractory Gastroparesis: Early Experience.

BACKGROUND: Gastric per oral endoscopic myotomy (G-POEM) of the pylorus is a technique that is recently being used to treat gastroparesis. Our aim was to report our experience in performing G-POEM for refractory gastroparesis of different etiologies and determine symptom improvement. METHODS: Thirteen patients undergoing G-POEM are reported. Pre- and post-procedure gastric emptying study (GES) and PAGI-SYM for symptom severity were obtained. Patients underwent G-POEM by creating a submucosal tunnel starting in the greater curvature of the distal antrum and extending it to the beginning of the duodenal bulb, followed by a full thickness pyloromyotomy. RESULTS: All 13 gastroparesis patients successfully underwent G-POEM (one diabetic [DGp], four idiopathic [IGp], eight postsurgical [PSGp]). Postsurgical patients included 4 s/p esophagectomy for esophageal cancer, 3 s/p Nissen fundoplication, and 1 s/p esophagectomy for achalasia. There were no procedure-related side effects. Of 11 patients completing follow-up questionnaires, eight were improved subjectively (four patients reported considerably better, four patients somewhat better, one unchanged, and two worse). Individual symptom severity scores tended to improve, particularly vomiting, retching, and loss of appetite. Of six patients that had post-G-POEM GES; GES improved in four, unchanged in one, and worsened in one). CONCLUSIONS: G-POEM for treatment of refractory gastroparesis appears to be a feasible and safe technique that can be successfully performed in patients with a variety of etiologies including different types of postsurgical gastroparesis. Our initial experience suggests that the majority of patients report some improvement in symptoms, particularly symptoms of vomiting, retching, and loss of appetite. Further experience is needed to determine the efficacy and safety of G-POEM and predict those who best respond to this treatment.

Domperidone to Treat Symptoms of Gastroparesis: Benefits and Side Effects from a Large Single-Center Cohort.

BACKGROUND: There is increased awareness about risks and benefits of using domperidone to treat gastroparesis. AIM: To describe the outcome of treating patients with refractory gastroparesis symptoms with domperidone. METHODS: Domperidone 10 mg QID or TID was prescribed to patients with refractory gastroparesis symptoms; follow-up obtained at 2-3 months assessing symptoms and side effects. Patients filled out Patient Assessment of Upper GI Symptoms prior to treatment and at follow-up along with Clinical Patient Grading Assessment Scale (CPGAS, +7 = completely better; 0 = no change). RESULTS: Of 125 patients initially prescribed domperidone, 7 did not take this medication and 3 were lost to follow-up. Of the 115 known patients treated with domperidone, 88 had idiopathic, 16 diabetic, and 9 postsurgical gastroparesis. Side effects were reported by 44 patients (most common-headache, tachycardia/palpitations, diarrhea); 14 patients stopped treatment. Hundred and one patients were seen at follow-up taking domperidone (2.4 ± 2.7 months, average dose 36 ± 13 mg/day). CPGAS averaged 2.7 ± 2.7 (p < 0.01) with 69 patients reporting symptom improvement and 45 patients at least moderately improved with CPGAS ≥ 4. Improvements were seen in most symptoms, especially postprandial fullness, nausea, vomiting, and stomach fullness. CONCLUSIONS: In this large single-center study of patients treated with domperidone, side effects necessitating discontinuing treatment occurred in 12 %. The majority of patients remaining on treatment experienced an improvement in symptoms of gastroparesis, particularly postprandial fullness, nausea, vomiting, and stomach fullness. Thus, domperidone treatment is beneficial for many patients with symptoms of gastroparesis. This study provides needed benefit and risk information concerning treating patients with domperidone. FDA IND Number: 71,089.

Pregnancy and postpartum bowel changes: constipation and fecal incontinence.

Pregnancy and the postpartum period are often associated with many gastrointestinal complaints, including nausea, vomiting, and heartburn; however, the most troublesome complaints in some women are defecatory disorders such as constipation and fecal incontinence, especially postpartum. These disorders are often multifactorial in etiology, and many studies have looked to see what risk factors lead to these complications. This review discusses the current knowledge of pelvic floor and anorectal physiology, especially during pregnancy, and reviews the current literature on causes and treatments of postpartum bowel symptoms of constipation and fecal incontinence.

The role of cannabinoids in regulation of nausea and vomiting, and visceral pain.

Marijuana derived from the plant Cannabis sativa has been used for the treatment of many gastrointestinal (GI) disorders, including anorexia, emesis, abdominal pain, diarrhea, and others. However, its psychotropic side effects have often limited its use. Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2, and possibly GPR55, have been identified throughout the GI tract. These receptors may play a role in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation, and cell proliferation in the gut. However, the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system has shed new knowledge in this field. Thus far, despite evidence of visceral sensitivity inhibition in animal models, data in irritable bowel syndrome (IBS) patients is scarce and not supportive. Furthermore, many compounds that either act directly at the receptor or increase (or reduce) ligand availability have the potential to affect other brain functions and cause side effects. Novel drug targets such as FAAH and monoacylglycerol lipase (MAGL) inhibitors appear to be promising in animal models, but more studies are necessary to prove their efficiency. The promise of emerging drugs that are more selective and peripherally acting suggest that, in the near future, cannabinoids will play a major role in managing an array of GI diseases.

Diabetes-related autoantibodies in diabetic gastroparesis.

BACKGROUND: Detection of islet autoantibodies [anti-glutamic acid decarboxylase antibody (GADA), anti-islet cell antibody (ICA), anti-insulin antibody (IAA)] in patients with diabetes usually indicates an autoimmune origin, suggesting type 1 diabetes (T1DM). The aim of our study was to determine whether islet autoantibodies are present in patients with diabetic gastroparesis and whether they associate with delayed gastric emptying, severity of GI symptoms, or diagnosed type of diabetes. METHODS: Patients with diabetic gastroparesis completed: (1) Demographic Questionnaire assessing type of diabetes, associated symptoms and control of glucose and (2) Patient Assessment of GI Symptoms assessing symptoms severity. Blood was drawn for GADA, anti-islet cell ICA-IAA, and Hgb-A1c. Medical records were reviewed for gastric emptying tests and to confirm type of diabetes. RESULTS: Sixteen patients (12 T1DM; 4 diagnosed T2DM) with diabetic gastroparesis were evaluated. Six of the 16 patients tested positive for GADA, but none were positive for either ICA or IAA. Five of 12 T1DM patients had positive GADA, compared to one of four diagnosed as T2DM. The presence of antibodies was associated with the age of onset of gastroparesis symptoms, but not related to gastric emptying delay, symptom severity, HBA1c levels, or age. CONCLUSIONS: This pilot study demonstrated that of the three tested antibodies in long-term diabetic gastroparesis patients, GADA was the most prevalent positive antibody with no detection of ICA or IAA. Positive GADA was seen in 42 % of T1DM compared to 25 % of phenotypic T2DM. However, the presence of antibody was not associated with severity of gastric emptying or GI symptoms. Thus, detection of an autoimmune form of diabetes, primarily T1DM, should be investigated using GADA.

Foods provoking and alleviating symptoms in gastroparesis: patient experiences.

BACKGROUND: Nutritional counseling for gastroparesis focuses on reduction of meal size, fiber, and fat to control symptoms. The tolerance of gastroparesis patients for particular foods is largely anecdotal. The aim of this study was to identify and characterize foods provoking or alleviating gastroparesis symptoms. METHODS: Gastroparesis patients completed: (1) Demographic Questionnaire; (2) Patient Assessment of Upper GI Symptoms; (3) Food Toleration and Aversion survey asking patients about experiences when eating certain foods utilizing a scale from -3 (greatly worsening symptoms) to +3 (greatly improving symptoms). Descriptive qualities (acidic, fatty, spicy, roughage-based, bitter, salty, bland, and sweet) were assigned to foods. RESULTS: Forty-five gastroparesis patients participated (39 idiopathic gastroparesis). Foods worsening symptoms included: orange juice, fried chicken, cabbage, oranges, sausage, pizza, peppers, onions, tomato juice, lettuce, coffee, salsa, broccoli, bacon, and roast beef. Saltine crackers, jello, and graham crackers moderately improved symptoms. Twelve additional foods were tolerated by patients (not provoking symptoms): ginger ale, gluten-free foods, tea, sweet potatoes, pretzels, white fish, clear soup, salmon, potatoes, white rice, popsicles, and applesauce. Foods provoking symptoms were generally fatty, acidic, spicy, and roughage-based. The foods shown to be tolerable were generally bland, sweet, salty, and starchy. CONCLUSIONS: This study identified specific foods that worsen as well as foods that may help alleviate symptoms of gastroparesis. Foods that provoked symptoms differed in quality from foods that alleviated symptoms or were tolerable. The results of this study illustrate specific examples of foods that aggravate or improve symptoms and provide suggestions for a gastroparesis diet.