Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis.

BACKGROUND & AIMS: Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear. METHODS: One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables. RESULTS: In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.).

Baseline Predictors of Longitudinal Changes in Symptom Severity and Quality of Life in Patients With Suspected Gastroparesis.

BACKGROUND & AIMS: Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis. METHODS: One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL. RESULTS: Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stools by Bristol stool form score, and presence of functional dyspepsia (FD) by Rome III criteria, were predictive of more severe upper GI symptoms. Even after controlling for these clinical factors, delayed gastric emptying by GES or WMC was associated with worse symptom severity and QOL scores. Low gastric and elevated small bowel contractile parameters by WMC were also independently associated with more severe upper GI symptoms and worse QOL scores. CONCLUSIONS: Baseline features, including demographic and clinical variables, delayed gastric emptying and abnormal gastrointestinal contractility, were independent predictors of more severe longitudinal symptoms and worse quality of life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no: NCT02022826.

Anorectal manometry for the diagnosis of pelvic floor disorders in patients with hypermobility spectrum disorders and hypermobile Ehlers-Danlos syndrome.

INTRODUCTION: Functional gastrointestinal disorders (FGID) including impaired rectal evacuation are common in patients with Hypermobility Spectrum Disorder (HSD) or Hypermobile Ehlers-Danlos Syndrome (hEDS). The effect of connective tissue pathologies on pelvic floor function in HSD/hEDS remains unclear. We aimed to compare clinical characteristics and anorectal pressure profile in patients with HSD/hEDS to those of age and sex matched controls. METHODS: We conducted a retrospective review of all FGID patients who underwent high resolution anorectal manometry (HR-ARM) and balloon expulsion test (BET) for evaluation of impaired rectal evacuation. Patients with HSD/hEDS were age and sex matched to a randomly selected cohort of control patients without HSD/hEDS. An abnormal BET was defined as the inability to expel a rectal balloon within 2 minutes. Wilcoxon rank sum test and Fisher's exact test were used to make comparisons and logistic regression model for predictive factors for abnormal evacuation. RESULTS: A total of 144 patients (72 with HSD/hEDS and 72 controls) were analyzed. HSD/hEDS patients were more likely to be Caucasian (p < 0.001) and nulliparous. Concurrent psychiatric disorders; depression, and anxiety (p < 0.05), and somatic syndromes; fibromyalgia, migraine and sleep disorders (p < 0.001) were more common in these patients. Rate of abnormal BET were comparable among the groups. HDS/hEDS patients had significantly less anal relaxation and higher residual anal pressures during simulated defecation, resulting in significantly more negative rectoanal pressure gradient. The remaining anorectal pressure profile and sensory levels were comparable between the groups. While diminished rectoanal pressure gradient was the determinant of abnormal balloon evacuation in non HSD/hEDS patients, increased anal resting tone and maximum volume tolerated were independent factors associated with an abnormal BET in HSD/hEDS patients. Review of defecography data from a subset of patients showed no significant differences in structural pathologies between HSD/hEDS and non HSD/hEDS patients. CONCLUSIONS: These results suggest anorectal pressure profile is not compromised by connective tissue pathologies in HSD patients. Whether concurrent psychosomatic disorders or musculoskeletal involvement impact the pelvic floor function in these patients needs further investigation.

Regional Gastrointestinal Transit and Contractility Patterns Vary in Postural Orthostatic Tachycardia Syndrome (POTS).

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder that affects multiple organs, including the gastrointestinal system. These patients often have multiple GI complaints with a severe impact on their quality of life. GI dysmotility patterns in POTS remains poorly understood and difficult to manage. AIMS: The aim of this study was to investigate the diagnostic yield of wireless motility capsule in patients with gastrointestinal symptoms and POTS, with use of a symptomatic control group without POTS as a reference. METHODS: We retrospectively reviewed the charts of patients who had both autonomic testing and wireless motility capsule between 2016 and 2020. The two groups were divided into those with POTS and those without POTS (controls) as diagnosed through autonomic testing. We compared the regional transit times and motility patterns between the two groups using the data collected from wireless motility capsule. RESULTS: A total of 25% of POTS patients had delayed small bowel transit compared to 0% of non-POTS patients (p = 0.047). POTS patients exhibited hypo-contractility patterns within the small bowel, including decreased contractions/min (2.95 vs. 4.22, p = 0.011) and decreased motility index (101.36 vs. 182.11, p = 0.021). In multivariable linear regression analysis, migraine predicted faster small bowel transit (p = 0.007) and presence of POTS predicted slower small bowel transit (p = 0.044). CONCLUSIONS: Motility abnormalities among POTS patients seem to affect mostly the small bowel and exhibit a general hypo-contractility pattern. Wireless motility capsule can be a helpful tool in patients with POTS and GI symptoms as it can potentially help guide treatment.

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.

Opioid Use and Potency Are Associated With Clinical Features, Quality of Life, and Use of Resources in Patients With Gastroparesis.

BACKGROUND & AIMS: Many patients with gastroparesis are prescribed opioids for pain control, but indications for opioid prescriptions and the relationship of opioid use to gastroparesis manifestations are undefined. We characterized associations of use of potent vs weaker opioids and presentations of diabetic and idiopathic gastroparesis. METHODS: We collected data on symptoms, gastric emptying, quality of life, and health care resource use from 583 patients with gastroparesis (>10% 4-h scintigraphic retention) from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Consortium, from January 2007 through November 2016. Patients completed medical questionnaires that included questions about opioid use. The opioid(s) were categorized for potency relative to oral morphine. Symptom severities were quantified by Patient Assessment of Upper Gastrointestinal Disorders Symptoms questionnaires. Subgroup analyses compared patients on potent vs weaker opioids and opioid effects in diabetic vs idiopathic etiologies. RESULTS: Forty-one percent of patients were taking opioids; 82% of these took potent agents (morphine, hydrocodone, oxycodone, methadone, hydromorphone, buprenorphine, or fentanyl). Abdominal pain was the reason for prescription for 61% of patients taking opioids. Mean scores for gastroparesis, nausea/vomiting, bloating/distention, abdominal pain, and constipation scores were higher in opioid users (P ≤ .05). Opioid use was associated with greater levels of gastric retention, worse quality of life, increased hospitalization, and increased use of antiemetic and pain modulator medications compared with nonusers (P ≤ .03). Use of potent opioids was associated with worse gastroparesis, nausea/vomiting, upper abdominal pain, and quality-of-life scores, and more hospitalizations compared with weaker opioids (tapentadol, tramadol, codeine, or propoxyphene) (P ≤ .05). Opioid use was associated with larger increases in gastric retention in patients with idiopathic vs diabetic gastroparesis (P = .008). CONCLUSIONS: Opioid use is prevalent among patients with diabetic or idiopathic gastroparesis, and is associated with worse symptoms, delays in gastric emptying, and lower quality of life, as well as greater use of resources. Potent opioids are associated with larger effects than weaker agents. These findings form a basis for studies to characterize adverse outcomes of opioid use in patients with gastroparesis and to help identify those who might benefit from interventions to prevent opioid overuse.

Validation of Diagnostic and Performance Characteristics of the Wireless Motility Capsule in Patients With Suspected Gastroparesis.

BACKGROUND & AIMS: It is a challenge to make a diagnosis of gastroparesis. There is good agreement in results from wireless motility capsule (WMC) analysis and gastric emptying scintigraphy (GES), but the diagnostic yield of WMC is unclear and the accuracy of this method has not been validated. We compared the performance characteristics of WMC vs GES in assessing gastric emptying in patients with suspected gastroparesis. METHODS: We performed a prospective study of 167 subjects with gastroparesis (53 with diabetes and 114 without) at 10 centers, from 2013 through 2016. Subjects were assessed simultaneously by GES and with a WMC to measure gastric emptying and regional transit. Delayed gastric emptying by GES was defined as more than 10% meal retention at 4 hrs whereas delayed gastric emptying by WMC was defined as more than 5 hrs for passage of the capsule into the duodenum; a severe delay in gastric emptying was defined as a gastric emptying time of more than 12 hrs by WMC or more than 35% retention at 4 hrs by GES. Rapid gastric emptying was defined as less than 38% meal retention at 1 hr based on by GES or gastric emptying times less than 1:45 hrs by WMC. We compared diagnostic and performance characteristics of GES vs WMC. RESULTS: Delayed gastric emptying was detected in a higher proportion of subjects by WMC (34.6%) than by GES (24.5%) (P=.009). Overall agreement in results between methods was 75.7% (kappa=0.42). In subjects without diabetes, the WMC detected a higher proportion of subjects with delayed gastric emptying (33.3%) than GES (17.1%) (P < .001). A higher proportion of subjects with diabetes had delayed gastric emptying detected by GES (41.7%) compared with non-diabetic subjects (17.1%) (P=.002). Severe delays in gastric emptying were observed in a higher proportion of subjects by WMC (13.8%) than by GES (6.9%) (P = .02). Rapid gastric emptying was detected in a higher proportion of subjects by GES (13.8%) than by WMC (3.3%) (P < .001). Regional and generalized transit abnormalities were observed in 61.8% subjects and only detected by WMC. CONCLUSION: Although there is agreement in analysis of gastric emptying by GES vs WMC, WMC provides higher diagnostic yield than GES. WMC detects delayed gastric emptying more frequently than GES and identifies extra-gastric transit abnormalities. Diabetic vs non-diabetic subjects have different results from GES vs WMC. These findings could affect management of patients with suspected gastroparesis. ClinicalTrials.gov no: NCT02022826.

Delayed Gastric Emptying Associates With Diabetic Complications in Diabetic Patients With Symptoms of Gastroparesis.

OBJECTIVES: Diabetic gastroparesis (Gp) occurs more often in type 1 diabetes mellitus (T1DM) than in type 2 diabetes mellitus (T2DM). Other diabetic end-organ complications include peripheral neuropathy, nephropathy, and retinopathy (together termed triopathy). This study determines the prevalence of diabetic complications (retinopathy, nephropathy, and peripheral neuropathy) in diabetic patients with symptoms of Gp, assessing the differences between T1DM and T2DM and delayed and normal gastric emptying (GE). METHODS: Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy. RESULTS: One hundred thirty-three diabetic patients with symptoms of Gp were studied: 59 with T1DM and 74 with T2DM and 103 with delayed GE and 30 without delayed GE. The presence of retinopathy (37% vs 24%; P = 0.13), nephropathy (19% vs 11%; P = 0.22), and peripheral neuropathy (53% vs 39%; P = 0.16) was not significantly higher in T1DM than in T2DM; however, triopathies (all 3 complications together) were seen in 10% of T1DM and 3% of T2DM (P = 0.04). Diabetic patients with delayed GE had increased prevalence of retinopathy (36% vs 10%; P = 0.006) and number of diabetic complications (1.0 vs 0.5; P = 0.009); however, 39% of diabetic patients with delayed GE did not have any diabetic complications. DISCUSSION: In diabetic patients with symptoms of Gp, delayed GE was associated with the presence of retinopathy and the total number of diabetic complications. Only 10% of patients with T1DM and 3% of those with T2DM had triopathy of complications, and 39% of diabetic patients with Gp did not have any diabetic complications. Thus, the presence of diabetic complications should raise awareness for Gp in either T1DM or T2DM; however, diabetic Gp frequently occurs without other diabetic complications.

A Positive Correlation Between Gastric and Esophageal Dysmotility Suggests Common Causality.

BACKGROUND: Gastric and esophageal dysmotility syndromes are some of the most common motility diagnoses, but little is known about their interrelationship. AIMS: The aim of our study was to determine if a correlation exists between gastric and esophageal dysmotility syndromes. METHODS: We reviewed the records of all patients who underwent both solid gastric emptying scintigraphy (GES) and high-resolution esophageal manometry (HRM) within a 2 year period, with both done between August 2012 and August 2017. All GESs were classified as either rapid, normal, or delayed. All HRMs were classified according to the Chicago Classification 3.0. Correlations were assessed using Fisher's exact test and multiple logistic regression. RESULTS: In total, 482 patients met inclusion criteria. Of patients with a normal, delayed, and rapid GES, 53.1, 64.5, and 77.3% had an abnormal HRM, respectively (p < 0.05 vs. normal GES). Likewise, patients with an abnormal HRM were more likely to have an abnormal GES (54.9 vs. 41.8%, p = 0.005). Multiple logistic regression showed abnormal GES [odds ratio (OR) 2.14], age (OR 1.013), scleroderma (OR 6.29), and dysphagia (OR 2.63) were independent predictors of an abnormal HRM. Likewise, an abnormal HRM (OR 2.11), diabetes (OR 1.85), heart or lung transplantation (OR 2.61), and autonomic dysfunction (OR 2.37) were independent predictors of an abnormal GES. CONCLUSIONS: The correlation between an abnormal GES and HRM argues for common pathogenic mechanisms of these motility disorders, and possibly common future treatment options. Clinicians should have a high index of suspicion for another motility disorder if one is present.

The integrated relaxation pressure may not be an appropriate gold standard for deglutitive relaxation due to reliance on a single intragastric reference sensor.

BACKGROUND: Integrated relaxation pressure (IRP) calculation depends on the selection of a single gastric reference sensor. Variable gastric pressure readings due to sensor selection can lead to diagnostic uncertainty. This study aimed to examine the effect of gastric reference sensor selection on IRP measurement and diagnosis. METHODS: We identified high-resolution manometry (HRM) conducted between January and November 2017 with at least six intragastric reference sensors. IRP measurements and Chicago Classification 3.0 (CCv3) diagnoses were obtained for each of six gastric reference sensors. Studies were categorized as "stable" (no change in diagnosis) or "variable" (change in diagnosis with gastric reference selection). Variable diagnoses were further divided into "variable normal/dysmotility" (≥1 normal IRP measurement and ≥1 CCv3 diagnosis), or "variable dysmotility" (≥1 CCv3 diagnosis, only elevated IRP measurements). Bland-Altman plots were used to compare IRP measurements within HRM studies. KEY RESULTS: The analysis included 100 HRM studies, among which 18% had variable normal/dysmotility, and 10% had variable dysmotility. The average IRP difference between reference sensors was 6.7 mmHg for variable normal/dysmotility and 5.9 mmHg for variable dysmotility. The average difference between the proximal-most and distal-most sensors was -1.52 mmHg (lower limit of agreement -10.03 mmHg, upper limit of agreement 7.00 mmHg). CONCLUSIONS & INFERENCES: IRP values can vary greatly depending on the reference sensor used, leading to inconsistent diagnoses in 28% of HRM studies. Choosing the correct gastric reference sensor is crucial for accurate test results and avoiding misdiagnosis. Standardization of reference sensor selection or supportive testing for uncertain results should be considered.

Whole Body Pain Distribution and Risk Factors for Widespread Pain Among Patients Presenting with Abdominal Pain: A Retrospective Cohort Study.

INTRODUCTION: Abdominal pain frequently co-occurs with pain in other body sites. Chronic overlapping pain conditions (COPCs) represent a group of widespread pain diagnoses. Our study characterized how patterns of somatic pain distribution are associated with COPCs and aimed to characterize predictors of widespread pain among patients with chronic abdominal pain. METHODS: This retrospective cohort study included adults presenting to a tertiary pain clinic, reporting abdominal pain at their initial visit, and with a follow-up visit at 12 months. Body maps divided patients into localized, intermediate, and widespread pain distribution patterns. Diagnostic and psychosocial measures were assessed across groups at the initial and follow-up visits. We analyzed the association of baseline diagnoses and demographics and time-varying changes in psychosocial measures from initial to follow-up visit with changes in pain distribution over time with alternating logistic regression (ALR). RESULTS: Among 258 patients, most were female (91.5%) and reported widespread pain (61.5%). Those with widespread pain at baseline reported elevated anger and 60.0% of patients remained in the same pain category at follow-up. Multivariable ALR demonstrated higher pain interference (AOR 1.06, 95% CI 1.02-1.10, P = 0.002), higher anxiety (AOR 1.05, 95% CI 1.01-1.09, P = 0.01), more than one COPC at initial visit (AOR 2.85, 95% CI 1.59-5.11, P = 0.0005), and initial visit widespread pain categorization (AOR 4.18, 95% CI 2.20-8.00, P < 0.0001) were associated with an increased risk of widespread pain at the follow-up visit. CONCLUSION: Most patients with abdominal pain report additional pain locations at multiple other body sites, and non-localized pain persists 12 months after pain treatment. Screening for widespread pain and COPC at the initial visit may identify patients at higher risk for persistent or new-onset widespread pain, and interventions to reduce pain interference and anxiety may promote reversal of widespread pain.

Baseline impedance via manometry and ambulatory reflux testing are not equivalent when utilized in the evaluation of potential extra-esophageal gastroesophageal reflux disease.

BACKGROUND: Esophageal baseline impedance (BI) shows promise for the diagnosis of gastroesophageal reflux disease (GERD), but means of acquisition and relevance to extra-esophageal manifestations of GERD (EE-GERD) remain unclear. In this study we aim to (I) evaluate concordance between BI as measured by 24-hour pH-impedance (pH-MII) and high-resolution impedance manometry (HRIM), and (II) assess relationship to potential EE-GERD symptoms. METHODS: In this prospective open cohort study, patients presenting for outpatient HRIM and pH-MII studies were prospectively enrolled. All patients completed the GERD-HRQL, NOSE, and respiratory symptom index questionnaire (RSI), plus questions regarding wheezing and dental procedures. HRIM and pH-MII were evaluated with calculation of BI. Correlations were assessed using either Pearson's correlation or Spearman's rank coefficients. RESULTS: 70 HRIM patients were enrolled, 35 of whom underwent pH-MII. There was no correlation between BI measurements as assessed by HRIM and pH-MII proximally, but there was moderate-weak correlation distally (r=0.34 to 0.5). Distal acid exposure time correlated with distal BI only for measurements by pH-MII (rho= -0.5 to -0.65), and not by HRIM. There was no relationship between proximal acid exposure time and proximal BI. There were no correlations when comparing proximal or distal BI measurements, acid exposure times, and impedance events to symptoms. CONCLUSIONS: Concordance between BI as measured by HRIM and pH-MII is poor, especially proximally, suggesting that these two methods are not interchangeable. There is no correlation between BI both distally/proximally and symptoms of either GERD/EE-GERD, suggesting that many symptoms are unrelated to acid or that BI is not an adequate marker to assess EE-GERD symptoms.

Satiety testing in diabetic gastroparesis: Effects of insulin pump therapy with continuous glucose monitoring on upper gastrointestinal symptoms and gastric myoelectrical activity.

BACKGROUND: Symptoms induced by caloric or non-caloric satiety test meals and gastric myoelectrical activity (GMA) have not been studied in patients with diabetic gastroparesis (DGP) before and after intense glucose management. AIMS: We determined the effects of continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM) on GI symptoms, volume consumed, and GMA induced by the caloric meal satiety test (CMST) and water load satiety test (WLST) in DGP. METHODS: Forty-five patients with DGP underwent CMST and WLST at baseline and 24 weeks after CSII with CGM. Subjects ingested the test meals until they were completely full. Visual analog scales were used to quantify pre- and postmeal symptoms, and GMA was recorded with cutaneous electrodes and analyzed visually and by computer. KEY RESULTS: At baseline and 24-week visits, nausea, bloating, abdominal discomfort, and fullness were immediately increased after CMST and WLST (Ps < 0.01). The meal volumes ingested were significantly less than normal controls at both visits in almost one-third of the subjects. After the CMST, the percentage 3 cycle per minute GMA increased and bradygastria decreased compared with WLST (Ps < 0.05). After treatment for 24 weeks meal volumes ingested, postmeal symptoms and GMA were no different than baseline. CONCLUSIONS AND INFERENCES: (a) Satiety test meals elicited symptoms of nausea, bloating, and abdominal discomfort; (b) CMST stimulated more symptoms and changes in GMA than WLST; and (c) CSII with CGM for 24 weeks did not improve symptoms, volumes ingested, or GMA elicited by the two satiety test meals in these patients with diabetic GP. Satiety tests in diabetic gastropresis are useful to study acute postprandial symptoms and GMA, but these measures were not improved by intensive insulin therapy.

High Prevalence of Slow Transit Constipation in Patients With Gastroparesis.

BACKGROUND/AIMS: Current evidence suggests the presence of motility or functional abnormalities in one area of the gastrointestinal tract increases the likelihood of abnormalities in others. However, the relationship of gastroparesis to chronic constipation (slow transit constipation and dyssynergic defecation) has been incompletely evaluated. METHODS: We retrospectively reviewed the records of all patients with chronic dyspeptic symptoms and constipation who underwent both a solid gastric emptying scintigraphy and a high-resolution anorectal manometry at our institution since January 2012. When available, X-ray defecography and radiopaque marker colonic transit studies were also reviewed. Based on the gastric emptying results, patients were classified as gastroparesis or dyspepsia with normal gastric emptying (control group). Differences in anorectal and colonic findings were then compared between groups. RESULTS: Two hundred and six patients met the inclusion criteria. Patients with gastroparesis had higher prevalence of slow transit constipation by radiopaque marker study compared to those with normal emptying (64.7% vs 28.1%, P = 0.013). Additionally, patients with gastroparesis had higher rates of rectocele (88.9% vs 60.0%, P = 0.008) and intussusception (44.4% vs 12.0%, P = 0.001) compared to patients with normal emptying. There was no difference in the rate of dyssynergic defecation between those with gastroparesis vs normal emptying (41.1% vs 42.1%, P = 0.880), and no differences in anorectal manometry findings. CONCLUSIONS: Patients with gastroparesis had a higher rate of slow transit constipation, but equal rates of dyssynergic defecation compared to patients with normal gastric emptying. These findings argue for investigation of possible delayed colonic transit in patients with gastroparesis and vice versa.

Gastric per-oral endoscopic myotomy: Current status and future directions.

Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis via endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.

Influence of Gastric Emptying and Gut Transit Testing on Clinical Management Decisions in Suspected Gastroparesis.

INTRODUCTION: Gastric emptying scintigraphy (GES) or wireless motility capsules (WMCs) can evaluate upper gastrointestinal symptoms in suspected gastroparesis; WMC tests can also investigate lower gut symptoms. We aimed to determine whether these tests impact treatment plans and needs for additional diagnostic evaluation. METHODS: In a prospective, multicenter study, 150 patients with gastroparesis symptoms simultaneously underwent GES and WMC testing. Based on these results, investigators devised management plans to recommend changes in medications, diet, and surgical therapies and order additional diagnostic tests. RESULTS: Treatment changes were recommended more often based on the WMC vs GES results (68% vs 48%) (P < 0.0001). Ordering of additional test(s) was eliminated more often with WMC vs GES (71% vs 31%) (P < 0.0001). Prokinetics (P = 0.0007) and laxatives (P < 0.0001) were recommended more often based on the WMC vs GES results. Recommendations for prokinetics and gastroparesis diets were higher and neuromodulators lower in subjects with delayed emptying on both tests (all P ≤ 0.0006). Laxatives and additional motility tests were ordered more frequently for delayed compared with normal WMC colonic transit (P ≤ 0.02). Multiple motility tests were ordered more often on the basis of GES vs WMC findings (P ≤ 0.004). Antidumping diets and transit slowing medications were more commonly recommended for rapid WMC gastric emptying (P ≤ 0.03). DISCUSSION: WMC transit results promote medication changes and eliminate additional diagnostic testing more often than GES because of greater detection of delayed gastric emptying and profiling the entire gastrointestinal tract in patients with gastroparesis symptoms. TRANSLATIONAL IMPACT: Gastric scintigraphy and WMCs have differential impact on management decisions in suspected gastroparesis.

Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis.

BACKGROUND: Idiopathic and diabetic gastroparesis in Homo sapiens cause significant morbidity. Etiology or risk factors have not been clearly identified. Failure to sustain elevated heme oxygenase-1 (HO1) expression is associated with delayed gastric emptying in diabetic mice and polymorphisms in the HO1 gene (HMOX1, NCBI Gene ID:3162) are associated with worse outcomes in other diseases. AIM: Our hypothesis was that longer polyGT alleles are more common in the HMOX1 genes of individuals with gastroparesis than in controls without upper gastrointestinal motility disorders. METHODS: Repeat length was determined in genomic DNA. Controls with diabetes (84 type 1, 84 type 2) and without diabetes (n = 170) were compared to diabetic gastroparetics (99 type 1, 72 type 2) and idiopathic gastroparetics (n = 234). Correlations of repeat lengths with clinical symptom sub-scores on the gastroparesis cardinal symptom index (GCSI) were done. Statistical analyses of short (<29), medium and long (>32) repeat alleles and differences in allele length were used to test for associations with gastroparesis. RESULTS: The distribution of allele lengths was different between groups (P = 0.016). Allele lengths were longest in type 2 diabetics with gastroparesis (29.18±0.35, mean ± SEM) and longer in gastroparetics compared to non-diabetic controls (28.50±0.14 vs 27.64±0.20 GT repeats/allele, P = 0.0008). Type 2 diabetic controls had longer alleles than non-diabetic controls. In all gastroparetic groups, allele lengths were longer in African Americans compared to other racial groups, differences in the proportion of African Americans in the groups accounted for the differences between gastroparetics and controls. Diabetic gastroparetics with 1 or 2 long alleles had worse GCSI nausea sub-scores (3.30±0.23) as compared to those with 0 long alleles (2.66±0.12), P = 0.022. CONCLUSIONS: Longer poly-GT repeats in the HMOX1 gene are more common in African Americans with gastroparesis. Nausea symptoms are worse in subjects with longer alleles.