Functional Dyspepsia and Gastroparesis.
Camilleri Michael
Digestive diseases (Basel, Switzerland)
BACKGROUND:Upper gastrointestinal disorders typically present with common symptoms. The most relevant non-mucosal diseases are gastroparesis, functional dyspepsia and rumination syndrome. The literature pertaining to these 3 conditions was reviewed. KEY MESSAGES:Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical obstruction of the stomach. The cardinal symptoms include postprandial fullness (early satiety), nausea, vomiting and bloating. The most frequently encountered causes of these symptoms are mechanical obstruction (pyloric stenosis), iatrogenic disease, gastroparesis, functional dyspepsia, cyclical vomiting and rumination syndrome. The most common causes of gastroparesis are neuropathic disorders such as diabetes, idiopathic, post-vagotomy and scleroderma among myopathic disorders. Principles of management of gastroparesis include exclusion of mechanical obstruction with imaging and iatrogenic causes with careful medication and past surgical history. Prokinetics and anti-emetics are the mainstays of treatment. Functional dyspepsia is characterized by the same symptoms as gastroparesis; in addition to delayed gastric emptying, pathophysiological abnormalities include accelerated gastric emptying, impaired gastric accommodation and gastric or duodenal hypersensitivity to distension and nutrients. Novel treatments include tricyclic antidepressants in patients with normal gastric emptying, acotiamide (acetyl cholinesterase inhibitor) and 5-HT1A receptor agonists such as buspirone. Rumination syndrome is characterized by repetitive regurgitation of gastric contents occurring within minutes after a meal. Episodes often persist for 1-2 h after the meal, and the regurgitant consists of partially digested food that is recognizable in its taste. Regurgitation is typically effortless or preceded by a sensation of belching. This has been summarized as a 'meal in, meal out, day in, day out' behavior for weeks or months, differentiating rumination from gastroparesis. Patients often have a background of psychological disorder or a prior eating disorder. Treatment is based on behavioral modification. CONCLUSION:Precise identification of the cause and pathophysiology of upper gastrointestinal symptoms is essential for optimal management.
10.1159/000445226
Laparoscopic pyloroplasty is a safe and effective first-line surgical therapy for refractory gastroparesis.
Shada Amber L,Dunst Christy M,Pescarus Radu,Speer Emily A,Cassera Maria,Reavis Kevin M,Swanstrom Lee L
Surgical endoscopy
INTRODUCTION:Surgical options for symptomatic delayed gastric emptying include gastric stimulator implantation, subtotal gastrectomy, and pyloroplasty. Pyloroplasty has been shown to improve gastric emptying yet is seldom described as a primary treatment for gastroparesis. We present a single-institution experience of laparoscopic Heineke-Mikulicz pyloroplasty (LP) as treatment for gastroparesis. METHODS AND PROCEDURES:A prospective foregut surgery database was queried for LP over a 5-year period. Charts were reviewed for indications, complications, symptom score, and outcomes. Gastroparesis was defined by (1) abnormal gastric emptying study, (2) endoscopic visualization of retained food after prolonged NPO status, or (3) clinical symptoms suspicious of vagal nerve injury following complex re-operative foregut surgery. Results were analyzed using a paired T test and single-factor ANOVA. RESULTS:One hundred and seventy-seven LP patients were identified and reviewed. One hundred and five had a concurrent fundoplication for objective reflux. There were no intraoperative complications or conversions to laparotomy. Overall morbidity rate was 6.8% with four return to OR and two confirmed leaks (1.1% leak rate). Average length of stay was 3.5 days, and readmission rate was 7%. Eighty-six percent had improvement in GES with normalization in 77%. Gastric emptying half-time decreased from 175 ± 94 to 91 ± 45 min. Nineteen patients (10.7%) had subsequent surgical interventions: gastric stimulator implantation (12), feeding jejunostomy and/or gastrostomy tube (6), or subtotal gastrectomy (4). Symptom severity scores for nausea, vomiting, bloating, abdominal pain, and early satiety decreased significantly at 3 months. CONCLUSION:Laparoscopic pyloroplasty improves or normalizes gastric emptying in nearly 90% of gastroparesis patients with very low morbidity. It significantly improves symptoms of nausea, vomiting, bloating, and abdominal pain. Some patients may go on to another surgical treatment for GP, but it remains a safe and less invasive alternative to a subtotal gastrectomy in these clinically challenging patients.
10.1007/s00464-015-4385-5
Management of gastroparesis-associated malnutrition.
Bharadwaj Shishira,Meka Krishna,Tandon Parul,Rathur Abdullah,Rivas John M,Vallabh Hiren,Jevenn Andrea,Guirguis John,Sunesara Imran,Nischnick Amy,Ukleja Andrew
Journal of digestive diseases
Gastroparesis (GP) is a chronic debilitating dysmotility characterized by unrelenting nausea, vomiting, bloating, early satiety, postprandial fullness and abdominal pain. Patients with GP experience other associated conditions, including gastroesophageal reflux disease, gastric bezoars and small bowel bacterial overgrowth. Furthermore, GP is associated with poor quality of life, increased emergency room visits, hospitalizations and subsequent increased healthcare costs. Currently, the managements of GP consist of glycemic control, antiemetics, prokinetics and the use of gastric electrical stimulation. However, most GP patients are at risk for significant nutritional abnormalities. As such, it is essential to screen and diagnose malnutrition in these patients. Poor oral intake in such patients could be supplemented by enteral tube feeding. Parenteral nutrition, although a last resort, is associated with a number of complications and should be used only for the short term. In summary, a systematic approach including initial nutritional screening, diet recommendations, medical therapy, nutritional re-evaluation and enteral and parental nutrition should be considered in complex GP patients.
10.1111/1751-2980.12344
[Gastroparesis - causes, diagnosis and treatment].
Sangnes Dag A,Søfteland Eirik,Biermann Martin,Gilja Odd Helge,Thordarson Hrafnkell,Dimcevski Georg
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke
BACKGROUND Gastroparesis is a motility disorder of the stomach. The symptoms are non-specific: nausea and vomiting are most common. Stomach pains, early satiety, postprandial fullness and bloating are also frequent symptoms. Current diagnostic criteria require delayed gastric emptying in the absence of any detectable mechanical obstruction. In this review article we elucidate the causes, assessment and treatment options.MATERIAL AND METHOD Structured article search in Embase and PubMed.RESULTS A number of conditions can lead to gastroparesis. The most frequent somatic cause is diabetes mellitus. Gastroparesis may also be iatrogenically inflicted by means of surgery or drugs. It may be difficult to discriminate between functional dyspepsia and idiopathic gastroparesis. Examination is based on patient history, gastroscopy and measurement of the rate of gastric emptying. Biochemical tests are also relevant for differential diagnosis. The treatment is primarily symptomatic, and consists of dietary measures, fluid therapy, drugs, gastric electrical stimulation, or endoscopic or surgical intervention in the form of insertion of a feeding tube for nutrition and abdominal relief, pyloroplasty or gastrectomy.INTERPRETATION Gastroparesis is a serious motility disorder. The condition may have significant consequences for patients, entailing reduced quality of life, reduced workforce participation and a considerable need for health assistance.
10.4045/tidsskr.15.0503
Upper Gastrointestinal Tract Motility Disorders in Women, Gastroparesis, and Gastroesophageal Reflux Disease.
Zia Jasmine K,Heitkemper Margaret M
Gastroenterology clinics of North America
This article reviews the sex differences in upper gastrointestinal (GI) motility for both healthy and common dysmotility conditions. It focuses on gastroesophageal reflux disease and other esophageal motor disorders for the esophagus and on gastroparesis and accelerated gastric emptying for the stomach. It also describes differences in upper GI motility signs and symptoms during each female hormonal stage (ie, menstrual cycle, pregnancy, perimenopause, menopause) for both healthy participants and those suffering from one of the aforementioned upper GI dysmotility conditions. More research still needs to be conducted to better understand sex differences in upper GI motility.
10.1016/j.gtc.2016.02.003
Emerging strategies for the treatment of gastroparesis.
Langworthy James,Parkman Henry P,Schey Ron
Expert review of gastroenterology & hepatology
Gastroparesis is a syndrome of delayed gastric emptying in the absence of mechanical obstruction. Symptoms can be debilitating, affect nutritional states, and significantly impact patients' quality of life. The management of these patients can prove quite difficult to many providers. This article will review the current management recommendations of gastroparesis, discuss investigational medications and interventions, and summarize future directions of therapies targeting the underlying disease process. Current therapies are subdivided into those improving gastric motility and those directly targeting symptoms. Non-pharmacologic interventions, including gastric stimulator implantation and intra-pyloric botulinum toxic injection are reviewed. A discussion of expert opinion in the field, a look into the future of gastroparesis management, and a key point summary conclude the article.
10.1586/17474124.2016.1150175
Safety of treatment for gastroparesis.
Sarosiek Irene,Bashashati Mohammad,McCallum Richard W
Expert opinion on drug safety
INTRODUCTION:Gastroparesis is a syndrome of chronic, often debilitating symptoms related to impaired gastric motility, resulting in delayed emptying of the stomach, within the setting of a documented absence of any mechanical obstruction in the upper gastrointestinal tract. This disorder manifests with the presence of early satiety, postprandial fullness, nausea, vomiting, bloating and abdominal pain. The past ten years have shown significant advances in knowledge of the pathophysiology of this entity as well as in new diagnostic tests. However, in the clinical world which requires treatment of gastroparetic symptoms, the pharmacological options have been limited and sometimes less than optimal. AREAS COVERED:This article provides an overview of the safety of the available pharmacological therapies utilized in the treatment of gastroparetic symptoms specifically addressing the safety of prokinetics, antiemetics, sensory neuromodulators and pain modifying agents. In addition, a brief overview of the evolving but yet to be officially approved agents is included. EXPERT OPINION:None of the medications used for the treatment of gastroparesis are devoid of side effects. Therefore, when prescribing these medications, the risk/benefit ratio should be considered. Since those agents are increasingly administered in combination, awareness of possible drug interactions must be considered in a setting of the patients' medical history, age, systemic diseases and other medications.
10.1517/14740338.2016.1173204
The impact of gastroparesis on diabetes control: Patient perceptions.
Homko Carol,Siraj Elias S,Parkman Henry P
Journal of diabetes and its complications
UNLABELLED:The impact of gastroparesis on diabetes management and control from the patient perspective has not been well characterized. The aim of this study was to identify patient perceptions regarding the impact of gastroparesis on managing their diabetes. METHODS:Patients with diabetes being referred for gastroparesis were enrolled in this prospective study. Gastroparetic symptom severity was assessed with the Patient Assessment of Upper GI Symptoms (PAGI-SYM). A questionnaire examined the impact of gastroparesis on diabetes related symptoms and control. RESULTS:54 diabetic gastroparesis patients (36 T1DM, 18 T2DM) participated. Duration of diabetes averaged 17.4±1.4years and gastroparetic symptoms 5.1±1.1years. Patients rated their most severe symptoms as postprandial fullness, early satiety, and nausea. Two thirds of diabetic subjects identified that since their diagnosis of gastroparesis, their diabetes was more difficult to control (44 of 54 patients) and that extra time and effort were required for care of their diabetes (45 of 54). Patients with T1DM, compared to those with T2DM, more often expressed that since developing gastroparesis, their blood sugars have been higher, they have had more frequent episodes of hypoglycemia, and they found that their gastroparetic symptoms worsened if blood sugars were too high. CONCLUSIONS:Gastroparesis has a significant impact on patients' perceived ability to self-manage and control their diabetes. T1DM patients, in particular, associate their gastroparesis with episodes of hyper- and hypo-glycemia, and find their gastroparetic symptoms worsen with poor control. Future research should focus on strategies to support self-management of patients with diabetic gastroparesis.
10.1016/j.jdiacomp.2016.03.025
Granisetron Transdermal System for Treatment of Symptoms of Gastroparesis: A Prescription Registry Study.
Midani Deena,Parkman Henry P
Journal of neurogastroenterology and motility
BACKGROUND/AIMS:Serotonin receptor (eg, 5-HT₃) antagonists are used to treat nausea and vomiting from a variety of causes. Granisetron transdermal system (GTS) is an appealing delivery system for patients with gastroparesis. To assess if GTS improves nausea and vomiting and other gastroparesis symptoms in patients with gastroparesis. METHODS:Patients with gastroparesis and symptoms of nausea and vomiting refractory to conventional treatment were treated with GTS. Symptoms of gastroparesis were assessed using a modified Gastroparesis Cardinal Symptom Index (GCSI). Following 2 weeks of treatment, patients were asked to assess their symptoms and indicate their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS) reporting if symptoms of nausea and vomiting improved on a scale: 0 = no change to +7 = completely better. RESULTS:Fifty-one patients received GTS by prescription: average age was 40 ± 17 years, 44 female, 11 diabetics, 23 ± 20% retention at 4 hours on gastric emptying scintigraphy. Thirty-nine of the 51 (76%) patients stated improvement with GTS. There was significant improvement in nausea and vomiting as assessed with CPGAS at 2 weeks (2.28 ± 2.53; < 0.05). Symptoms of nausea and vomiting significantly improved. Other symptoms including postprandial fullness, loss of appetite, upper abdominal pain, and early satiety improved. Side effects reported included redness at the site of the patch in 7 patients, pruritus in 5, and constipation in 5. CONCLUSIONS:GTS was moderately effective in reducing nausea and/or vomiting in 76% of gastroparesis patients. In addition to nausea and vomiting, symptoms of postprandial fullness, loss of appetite, upper abdominal pain, and early satiety also improved.
10.5056/jnm15203
Domperidone to Treat Symptoms of Gastroparesis: Benefits and Side Effects from a Large Single-Center Cohort.
Schey Ron,Saadi Mohammed,Midani Deena,Roberts Aaron C,Parupalli Rahul,Parkman Henry P
Digestive diseases and sciences
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.
10.1007/s10620-016-4272-5
Chronic Unexplained Nausea and Vomiting or Gastric Neuromuscular Dysfunction (GND)? An Update on Nomenclature, Pathophysiology and Treatment, and Relationship to Gastroparesis.
Current treatment options in gastroenterology
OPINION STATEMENT:Chronic unexplained nausea and vomiting is a debilitating condition that dramatically decreases patient quality of life and creates diagnostic and treatment challenges for healthcare providers. Additionally, the significant overlap in symptoms between disorders such as chronic unexplained nausea and vomiting, gastroparesis, and functional dyspepsia has resulted in a blurring of diagnostic lines and added confusion to the therapeutic approach. The identified overlap in clinical symptoms also suggests a common underlying pathophysiological mechanism may drive these conditions, indicating they could possibly be part of a spectrum of gastric neuromuscular disorders instead of discrete processes. This article will discuss the classification, updates in pathophysiology and therapeutic research, and future directions of research in the treatment of chronic unexplained nausea and vomiting.
10.1007/s11938-016-0113-z
Systematic review and meta-analysis: Gastric electrical stimulation for gastroparesis.
Levinthal D J,Bielefeldt K
Autonomic neuroscience : basic & clinical
BACKGROUND:Controlled trials of gastric electrical stimulation (GES) for gastroparesis reported no significant improvement in symptoms, while open label studies suggested substantial clinical benefits. AIM:To determine if GES is effective in reducing symptoms in patients with gastroparesis. METHODS:We searched PubMed and Embase for articles published in English (1990-2014) using "gastroparesis" as a search term restricted to "clinical trial". We included studies describing repeated patient-based symptom ratings before and during standardized treatments of at least one week duration. RESULTS:Five studies randomly allocated patients to periods with or without GES. Total symptom severity (TSS) scores did not differ between these periods (0.17 [95% confidence interval: -0.06 to 0.4]; P=0.15). However, sixteen open label studies of GES showed a significant TSS decrease (2.68 [2.04-3.32]; Q=39.0; P<0.001). Other treatment modalities similarly improved TSS by 1.97 [1.5-2.44] for medical therapy (MED), by 1.52 [0.9-2.15] for placebo arms (PLA), and by 2.32 [1.56-3.06] for botulinum toxin (BTx). There were significant differences in baseline TSS ratings among these studies (GES: 6.28 [6.28-7.42]; MED: 4.76 [4.09-5.42]; PLA: 4.59 [3.77-5.42]; BTx: 6.02 [5.3-6.74]; Q=35.1; P<0.001). Meta-regression analysis showed these baseline differences to significantly impact TSS ratings during treatment (Q=71.8; P<0.001). CONCLUSION:Independent of the treatment modality, baseline symptom severity impacts treatment results in gastroparesis. Considering the skewed population with refractory symptoms, regression to the mean likely contributes to the substantial discrepancies between the reported results of controlled and open label GES studies, raising questions about the use of GES outside of defined clinical trials.
10.1016/j.autneu.2016.03.004
Treating an oft-unrecognized and troublesome entity: using gastric electrical stimulation to reduce symptoms of malignancy-associated gastroparesis.
Shah Hamza,Wendorf Gregg,Ahmed Shifat,McElmurray Lindsay,Lahr Chris,Hughes Michael,Beauerle Brian,Miller Ed,Stocker Abigail,Abell Thomas L
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
PURPOSE:Malignancy-associated gastroparesis (MAG) is a cause of morbidity in cancer patients but therapies are lacking. Gastric electrical stimulation (GES) is a novel treatment for MAG. Here, we describe 19 patients with MAG who underwent temporary GES placement. PATIENTS AND METHODS:Nineteen patients (6 males, 13 females) with various malignancies were reviewed for symptom scores and physiologic measures at baseline and after temporary GES placement. Symptoms were scored by three variables: nausea (N), vomiting (V), and GI total symptom score (TSS). Physiologic profiles were measured by solid and liquid phase gastric emptying scans (GET) at 1, 2, and 4 h and cutaneous electrogastrogram (EGG) and mucosal electrogram (EG) frequencies. Symptoms were measured for 5 days after temporary endoscopic GES placement, and measures were repeated post GES placement. RESULTS:Baseline GET results displayed delayed gastric emptying in 16 of 19 patients (mean solid retention 21.7 % at 4 h, normal <10 %; mean liquid retention 10.4 % at 4 h, normal <5 %). Cutaneous EGG (mean frequency 5.5 cpm) and EG (mean proximal frequency 5.1 cpm; mean distal frequency 5.1 cpm) showed evidence of neuromuscular dysfunction (normal 2.5-3.3 cpm). Symptom scores in N, V, and TSS showed statistically significant reduction after GES placement. CONCLUSION:A small sample of patients with MAG and receiving temporary GES experienced symptom improvement, with less change on gastric emptying time or gastric electrical amplitude or frequency. GES may provide a potential therapeutic option for symptomatic management of MAG and evaluation of these MAG patients after permanent GES placement is ongoing. Prospective studies of MAG using temporary and permanent GES may be warranted.
10.1007/s00520-016-3375-z
Epidemiology and Pathophysiology of Gastroparesis.
Moshiree Baha,Potter Michael,Talley Nicholas J
Gastrointestinal endoscopy clinics of North America
Gastroparesis is a complex syndrome with symptoms that include nausea, vomiting, and postprandial abdominal pain, and is frequently accompanied by significant delays in gastric emptying. The pathophysiology of diabetic gastroparesis is fairly well understood; however, idiopathic gastroparesis, which accounts for one-third of all cases, may stem from infections, or autoimmune or neurologic disorders, among other causes. To date, few population-based studies have estimated the true prevalence and incidence of gastroparesis. Nonetheless, its prevalence appears to be rising, as does its incidence among minority populations, documented via hospitalizations, which can impose significant economic burdens on patients.
10.1016/j.giec.2018.08.010
Evaluation of Patients with Suspected Gastroparesis.
Szarka Lawrence A,Camilleri Michael
Gastrointestinal endoscopy clinics of North America
There is substantial overlap between the symptoms of gastroparesis and a variety of alternative disorders. These conditions include rumination syndrome, drug-induced gastric emptying delay, cannabinoid hyperemesis syndrome, and eating disorders, which can be identified based on the history alone. The remaining patients require a diagnostic approach of physical examination, laboratory tests, evaluation with esophagogastroduodenoscopy or contrast radiography, and a test to measure gastric emptying. Symptomatic patients who have normal nutritional status and gastric emptying that is either normal or mildly delayed should be diagnosed with functional dyspepsia, whereas patients with moderate or severe gastric emptying delay are diagnosed with gastroparesis.
10.1016/j.giec.2018.08.004
Gastric Electrical Stimulator for Treatment of Gastroparesis.
Atassi Hadi,Abell Thomas L
Gastrointestinal endoscopy clinics of North America
Patients with gastroparesis sometimes suffer from intractable nausea and vomiting, abdominal pain, and bloating, as well as a host of other symptoms that can often be difficult to control. Initially, patients are treated conservatively; some do well with conservative management but unfortunately some do not. Over the years, studies have shown the benefits of gastric electrical stimulation, which often results in symptomatic improvement and improvement in gastric emptying times. This article discusses the history of gastric electrical stimulation and its use in clinical practice to help those suffering from gastroparesis that is refractory to conservative medical management.
10.1016/j.giec.2018.08.013
Botulinum Toxin Injection for Treatment of Gastroparesis.
Pasricha Trisha S,Pasricha Pankaj J
Gastrointestinal endoscopy clinics of North America
Refractory gastroparesis is among the most difficult therapeutic challenges in gastroenterology. Pyloric dysfunction has been described in a subset of patients with gastroparesis, prompting experimentation with botulinum toxin injections into the pylorus, which is relatively safe and has been successfully used in other gastrointestinal disorders. However, causality between pyloric dysfunction and symptoms of gastroparesis has never been demonstrated. Although several open-label studies showed initial promise, 2 randomized clinical trials failed to elicit a difference in clinical outcomes in botulinum toxin versus placebo. Based on current evidence, further use of botulinum toxin for gastroparesis is discouraged outside of a research trial.
10.1016/j.giec.2018.08.007
Gastroparesis and Functional Dyspepsia: A Blurring Distinction of Pathophysiology and Treatment.
Kim Beom Jin,Kuo Braden
Journal of neurogastroenterology and motility
Gastroparesis and functional dyspepsia are 2 of the most common gastric neuromuscular disorders. These disorders are usually confused, having both similarities and differences. The pathophysiology of these disorders involves abnormal gastric motility, visceral hypersensitivity, mucosal inflammation, and various cellular changes. Both disorders have similar symptoms such as epigastric pain or discomfort, early satiety, and bloating. If patients suspected of having either gastroparesis or functional dyspepsia present with upper gastrointestinal symptoms, they should undergo upper endoscopy to exclude an alternative organic cause. Although the gastric emptying rate is frequently assessed during the clinical workup of patients with gastroparesis or functional dyspepsia, the correlation between gastric emptying and the symptoms is generally poor. Once the diagnosis of gastroparesis or functional dyspepsia is made, treatment should focus on the predominant symptom. Recently, various treatment modalities have been developed and validated. Prokinetic agents are generally used as treatment for both gastroparesis and functional dyspepsia. Acid-suppressive therapy, eradication, and use of drugs that enhance gastric accommodation are employed for functional dyspepsia. Psychoactive drugs are also effective in symptom control. For gastroparesis, antiemetic agents, ghrelin receptor agonists, and serotonergic agents are used aside from prokinetic agents. Acupuncture and gastric electrical stimulation can be attempted. In severe cases, endoscopic and surgical interventions are considered for symptom control.
10.5056/jnm18162
Diabetic Gastroparesis and Nondiabetic Gastroparesis.
Gastrointestinal endoscopy clinics of North America
Gastroparesis can be divided into diabetic and nondiabetic, and the 3 main causes of gastroparesis are diabetic, postsurgical, and idiopathic. Delayed gastric emptying is the main manifestation of motility disorders for gastroparesis. Symptoms of gastroparesis are nonspecific and severity can vary. Nausea and vomiting are more common in diabetic gastroparesis whereas abdominal pain and early satiety are more frequent in idiopathic gastroparesis. Medication is still the mainstay of treatment of gastroparesis; however, the development of gastric electric stimulation and gastric peroral endoscopic pyloromyotomy brings more options for the treatment of diabetic and nondiabetic gastroparesis.
10.1016/j.giec.2018.08.002
Clinical Manifestation and Natural History of Gastroparesis.
Loganathan Priyadarshini,Gajendran Mahesh,McCallum Richard W
Gastrointestinal endoscopy clinics of North America
Although gastroparesis was described more than 60 years ago, the natural history and the long-term outcome are still being clarified. The patients with more severe gastroparesis often seek health care treatment in university medical centers specializing in gastrointestinal motility disorders and hence reports in the literature tend to be based on this population and may not be representative of the entire spectrum. The clinical manifestations of gastroparesis are heterogeneous but a significant proportion of patients end up with substantially poorer quality of life. In this article, the focus is on the clinical presentation and natural history of gastroparesis.
10.1016/j.giec.2018.08.003
Gastric Electric Stimulation for Refractory Gastroparesis.
Journal of clinical outcomes management : JCOM
OBJECTIVE:To outline the use and utility of gastric electric stimulation (GES) as a therapeutic intervention for gastroparesis. METHODS:Review of the literature. RESULTS:Gastroparesis is characterized by delayed gastric emptying, with symptoms of nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. Some patients with gastroparesis do not respond to medical intervention, and for these patients surgical intervention may be warranted. GES utilizes high-frequency gastric neurostimulation to facilitate gastric emptying and reduce symptoms of gastroparesis. It is indicated for patients with idiopathic and diabetic gastroparesis who have nausea and vomiting as their primary symptoms and who have not responded to medical therapy. GES has also been used in postsurgical and pediatric gastroparesis patients. Optimizing the outcome of this surgical treatment through proper patient selection and meticulous surgical technique is essential as there are inherent risks to the procedure. Nonblinded studies of GES for medically refractory gastroparesis have demonstrated therapeutic symptomatic benefit, whereas randomized controlled trials have not. New interventions such as pyloromyotomy and pyloroplasty are reasonable alternatives or addendums to GES. CONCLUSION:GES may be considered among the therapies available for treating patients with refractory symptoms of gastroparesis. More studies, specifically those comparing GES, pyloromyotomy, GES combined with pyloromyotomy, and placebo, are needed to help guide therapy selection for refractory gastroparesis.
Development and psychometric evaluation of the Diabetic Gastroparesis Symptom Severity Diary.
Fehnel Sheri,Fiedorek Fred T,Nelson Lauren,DiBenedetti Dana,Spence Sharon,Carson Robyn T
Clinical and experimental gastroenterology
BACKGROUND:Diabetic gastroparesis (DG) is defined as delayed gastric emptying with associated gastrointestinal symptoms, without mechanical obstruction. Patient-reported symptoms are critical for diagnosis and evaluation of treatment benefit in DG. The Diabetic Gastroparesis Symptom Severity Diary (DGSSD), a new patient-reported outcome measure, was developed for use in clinical trials to support product approval and labeling claims for DG treatments. MATERIALS AND METHODS:Initial DGSSD development was based on a review of the existing instruments and qualitative research (focus groups and cognitive debriefing interviews) in 41 patients with DG. Psychometric evaluations (individual items and composite scores) were conducted using data from Phase IIa and IIb relamorelin clinical trials. RESULTS:Qualitative research in patients with DG resulted in a six-item DGSSD, included in the Phase IIa trial, addressing symptom severity for nausea, vomiting, abdominal pain, early satiety, and bloating, as well as vomiting frequency. An item addressing severity of postprandial fullness (PPF) was subsequently added based on regulatory advice and included in the Phase IIb trial. Measurement properties were generally strong for weekly averages of daily item and composite scores. Item-level intraclass correlation coefficients ranged from 0.79 to 0.97 and correlations with other measures matched hypothesized patterns; the discriminating ability and responsiveness of the DGSSD were also supported. Multiple methods supported the computation of a composite score based on items addressing nausea, abdominal pain, bloating, and PPF severity. CONCLUSION:Qualitative and quantitative evidence support use of the DGSSD as a reliable and valid measure from which to derive endpoints to evaluate treatment benefit in future DG interventional trials.
10.2147/CEG.S184016
Emergency Department Burden of Gastroparesis in the United States, 2006 to 2013.
Hirsch William,Nee Judy,Ballou Sarah,Petersen Travis,Friedlander Daniel,Lee Ha-Neul,Cheng Vivian,Lembo Anthony
Journal of clinical gastroenterology
BACKGROUND AND AIMS:Gastroparesis, a chronic gastrointestinal disorder defined by delayed stomach emptying in the absence of obstruction, is often associated with frequent and costly visits to the emergency department (ED). The aim of this study was to analyze trends in gastroparesis-related ED visits from 2006 to 2013. MATERIALS AND METHODS:Patients with a primary diagnosis of gastroparesis were identified from the Nationwide Emergency Department Sample (NEDS), the largest publicly available ED all-payer representative database in the United States. ED visits, admission rates, duration of hospitalizations, and charges were compiled. Patients with a secondary diagnosis of diabetes mellitus were analyzed as a subgroup. RESULTS:The number of ED visits for gastroparesis as a primary diagnosis in the United States increased from 15,459 in 2006 to 36,820 in 2013, an increase from 12.9 to 27.3 per 100,000 ED visits. The total charges associated with these ED visits and subsequent admissions increased from $286 million to $592 million. In contrast, admission rates through the ED decreased by 22%, procedure rates decreased by 6.2%, and the mean length of stay was shortened by 0.6 days. ED visits for patients with diabetic gastroparesis increased from 5696 to 14,114, an increase from 4.7 to 10.5 per 100,000 ED visits, with an increase in total associated charges for ED visits and subsequent admissions from $84 million to $182 million. CONCLUSIONS:The number of ED visits and associated charges for a primary diagnosis of gastroparesis with or without a secondary diagnosis of diabetes mellitus rose significantly from 2006 to 2013.
10.1097/MCG.0000000000000972
Gastroparesis syndromes: Response to electrical stimulation.
Abell Thomas L,Kedar Archana,Stocker Abigail,Beatty Karen,McElmurray Lindsay,Hughes Michael,Rashed Hani,Kennedy William,Wendelschafer-Crabb Gwen,Yang Xiu,Fraig Mostafa,Omer Endashaw,Miller Ed,Griswold Michael,Pinkston Christina
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND AND AIMS:Factors underlying gastroparesis are not well defined, nor is the mechanism of action of gastric electrical stimulation (GES). We hypothesized that GES acts via several mechanisms related to underlying disordered pathophysiology. METHODS:We studied 43 consecutive eligible patients with gastroparetic symptoms, previously evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal; and also categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. We then studied 41 patients who underwent temporary GES for 5-7 days. Thirty-six of those patients were implanted and 30 were followed up at 6 months after permanent GES. RESULTS:In previous but separately reported work, patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status and all patients demonstrated abnormalities in each of the five areas studied. After GES, patients showed early and late effects of electrical stimulation with changes noted in multiple areas, categorized by improvement status. CONCLUSION:Patients with symptoms of gastroparesis have multiple abnormalities, including systemic inflammation and disordered hormonal status. GES affects many of these abnormalities. We conclude electrical stimulation improves symptoms and physiology with (a) an early and sustained anti-emetic effect; (b) an early and durable gastric prokinetic effect in delayed emptying patients; (c) an early anti-arrhythmic effect that continues over time; (d) a late autonomic effect; (e) a late hormonal effect; (f) an early anti-inflammatory effect that persists; and (g) an early and sustained improvement in health-related quality of life. This study is registered with Clinicaltrials.gov under study # NCT03178370 (https://clinicaltrials.gov/ct2/show/NCT03178370).
10.1111/nmo.13534
Occult Non-small Cell Lung Cancer Presenting as Paraneoplastic Gastroparesis: A Case Report and Literature Review.
Baig Muhammad A,Randhawa Tejinder,Majeed Muhammad B,Agrawal Rohit,Gandhi Seema R
Cureus
Paraneoplastic gastrointestinal syndromes rarely precede the actual detection of an overt cancer with gastroparesis being a very rare initial presentation. To increase the clinical awareness of this rare clinical entity, we present a case of severe gastroparesis that was later proven to be associated with an occult poorly differentiated non-small cell lung cancer. We then continue to briefly review the relevant literature on paraneoplastic gastrointestinal syndromes to date. A 61-year-old African-American man presented with two months history of severe post-prandial nausea, vomiting and bloating associated with unintentional weight loss of 20 pounds. General physical examination revealed cachexia, temporal muscle wasting and clubbing of nails in both hands. The following investigations were normal or negative: basic metabolic panel, liver function tests, chest X-ray and esophagogastroduodenoscopy. Computed tomography (CT) scan of the abdomen showed residual food in the stomach and scintigraphic gastric emptying studies were consistent with gastroparesis. CT scan of the chest was performed which revealed a spiculated nodule sized 9 mm in right upper lobe of the lung with right hilar lymphadenopathy. Positron emission tomography (PET) scan revealed hyper-metabolic activity in the right upper lobe nodule and right hilar adenopathy. Nodule resection and biopsy revealed a poorly differentiated non-small cell lung carcinoma. Due to the concern of paraneoplastic origin of his gastroparesis further serological testing showed positive anti-neuronal nuclear antibodies type 1 (Anti-Hu) and cytoplasmic purkinje cell antibodies (Anti-Yo). The patient was started on a chemotherapy combination of Carboplatin and Paclitaxel with a three-week course of local radiation therapy. Moreover, for the relief of his severe gastrointestinal (GI) symptoms dietary modifications, pro-kinetic agents and psychological counseling were used with gradual clinical improvement observed on follow-up visits.
10.7759/cureus.4216
The American neurogastroenterology and motility society gastroparesis cardinal symptom index-daily diary (ANMS GCSI-DD): Psychometric evaluation in patients with idiopathic or diabetic gastroparesis.
Revicki Dennis A,Speck Rebecca M,Lavoie Sara,Puelles Jorge,Kuo Braden,Camilleri Michael,Almansa Cristina,Parkman Henry P
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:The purpose of this study was to evaluate the measurement properties of the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary, a patient-reported outcome instrument developed to meet US FDA recommendations for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score from none (0) to very severe (4) and number of vomiting episodes during the past 24 hours. The composite score includes the first four symptoms, the core symptom score includes all five symptoms. METHODS:Seventy-one patients diagnosed with idiopathic or diabetic gastroparesis were recruited for a four-week observational study. Patients completed the ANMS GCSI-DD at home between Baseline and Week 4. Statistical analyses included confirmatory factor analysis, item response theory analysis, internal consistency, test-retest reliability, and construct and known-groups validity. KEY RESULTS:Unidimensionality for the composite and core symptom scores was supported, and items exhibited good fit. Internal consistency (Cronbach's alpha =0.85 and 0.83) and test-retest reliability were 0.89 and 0.88, for composite and core symptom scores, respectively. Convergent validity was supported by strong correlations with patient-reported and clinician measures. Baseline and Week 4 scores differed for three measures used to define disease severity status (P < 0.0001), supporting known-groups validity. CONCLUSIONS & INFERENCES:The ANMS GCSI-DD has excellent reliability and validity, supporting its use to assess symptom-based endpoints in gastroparesis clinical studies. Further analyses will be conducted using clinical trial data to ascertain treatment responsiveness and define a responder.
10.1111/nmo.13553
High Prevalence of Slow Transit Constipation in Patients With Gastroparesis.
Zikos Thomas A,Kamal Afrin N,Neshatian Leila,Triadafilopoulos George,Clarke John O,Nandwani Monica,Nguyen Linda A
Journal of neurogastroenterology and motility
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%, = 0.013). Additionally, patients with gastroparesis had higher rates of rectocele (88.9% vs 60.0%, = 0.008) and intussusception (44.4% vs 12.0%, = 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%, = 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.
10.5056/jnm18206
Temporary Gastric Stimulation in Patients With Gastroparesis Symptoms: Low-Resolution Mapping Multiple Versus Single Mucosal Lead Electrograms.
Gastroenterology research
BACKGROUND:Cajal cells have a fundamental role in generating slow waves that regulate gastric motility. Gastric electrical stimulation (GES) is Food and Drug Administration (FDA)-approved for symptomatic treatment of drug refractory gastroparesis. We hypothesized that using two leads will vary from a single lead by providing greater insight of gastric electrical wave propagation, through differences in measured frequency, amplitude, and frequency over amplitude ratio. We also hypothesized that a significant reduction in symptomatic vomiting score is highly predictive in a single lead temporary gastric electrical stimulation. METHODS:A total of 111 patients with drug-refractory gastroparesis were enrolled. Forty-two patients had single lead, while 69 patients had two leads. All recordings measured mean frequency and amplitude in each lead. Patients documented symptoms using standardized symptom scores at baseline and day 5 post-procedure. RESULTS:Single lead patients with initial low mucosal frequency showed an increase from 3.10 to 4.93 (P = 0.0155), while the high frequency group decreased from 5.89 to 5.12 (P = 0.135). Vomiting score decreased significantly among both groups with GES (P = 0.0001). For two leads, the mucosal frequency decreased at the proximal electrode (P = 0.402), and increased at the distal electrode (P = 0.514), neither statistically significant (P = 0.143). Mucosal electrogram amplitude values changed for both proximal, mean decrease of 0.34 mV (P = 0.241), and distal, mean increase of 0.05 mV (P = 0.65) with a mean difference 0.34 mV (P = 0.238). However, mucosal electrogram frequency and amplitudes on day 5 were highly dependent on the baseline values (P < 0.001). CONCLUSIONS:Compared to the use of single point electrodes, the use of two low-resolution electrodes allows recording gastric electrical wave propagation with greater detail. Low resolution recording appears to be superior to single point recordings, while awaiting practical high-resolution recordings.
10.14740/gr1127
Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation.
Omer Endashaw,Kedar Archana,Nagarajarao Harsha S,Nikitina Yana,Vedanarayanan Vetta,Subramony Charu,Lahr Christopher J,Abell Thomas L
Journal of clinical gastroenterology
BACKGROUND AND AIMS:Cajal cells serve as the pacemaker cells of the gastrointestinal tract and regulates peristalsis. On the baisis of that fact, it has been hypothesized that a decrease in Cajal cells can lead to gastroparesis and other motility issues. Treatment with medications has a limited efficacy and most resort to gastric electrical stimulation (GES) devices for symptomatic relief. We believe that the number of Cajal cells present is directly proportional to symptomatic relief with GES. MATERIALS AND METHODS:Twenty-three (white female) subjects were recruited from the gastric motility clinic University of Mississipi for this study with the criteria of drug refractory gastropersis. Symptoms were measured using Likert scale and gastric emptying times were measured pre-GES and post-GES. Serosal electrogram measurements were recorded during surgical placement of permanent electrical stimulator under various modes. Cajal cell count scoring via immunohistochemistry were performed during the implantaion of the GES. RESULTS:The data were grouped in 2 categories based on the Cajal cells that is ≥2.00 and <2.00. Subjects with higher Cajal cells reported a statiscially improvement in gastroperesis symptoms. Significant differences were also noted in the first hour gastric emptying study. The mean group difference is 17.5 (95% confidence interval, 1.41-33.58; P=0.035). Serosal amplitude differences were noted being significantly higher in the group with ≥2 cajal cells. CONCLUSIONS:Electrograms obtained after GES demonstrates immediate improvement in gastric electrical activity and gastroparesis symptoms in patients with relatively higher Cajal cell counts when compared with patients with extensive loss of Cajal cells.
10.1097/MCG.0000000000001025
Effects of AMPK on Apoptosis and Energy Metabolism of Gastric Smooth Muscle Cells in Rats with Diabetic Gastroparesis.
Zhang Mo-Han,Fang Xue-Sen,Guo Jun-Yu,Jin Zheng
Cell biochemistry and biophysics
This study aimed to investigate the effect of AMPK on apoptosis and energy metabolism of gastric smooth muscle cells in diabetic rats and to explore the role of AMPK in the pathogenesis of diabetic gastroparesis (DGP). After establishment of a diabetic rat model, rats were divided into normal control (NC), 4-week (DM4W), 6-week (DM6W), and 8-week (DM8W) diabetic model groups. The gastric residual pigment ratio, intestinal transit rate, and intestinal propulsion rate in each group were detected to confirm the successful establishment of the DGP model. The spontaneous contraction in isolated gastric smooth muscle strips of the NC and DM8W groups was experimentally observed. The expression of phospho-AMPK, AMPK, phospho-LKB1, LKB1, phospho-TAK1, TAK1, and CaMMKβ in rat gastric smooth muscle tissues was detected by western blot analysis; ADP, AMP, ATP contents, and the energy charge were detected using Elisa; and apoptosis of gastric smooth muscle cells was detected by flow cytometry. The rat gastric smooth muscle cells were cultured in vitro, and treated with an AMPK inhibitor and an agonist. At 24 and 48 h, the effects of AMPK on apoptosis and energy metabolism of gastric smooth muscle cells were observed. Reduced spontaneous contractions, AMPK activation, cell apoptosis, and energy metabolism disorders were observed in gastric smooth muscle tissues of a diabetic rat, and AMPK activation was associated with an increased ratio of ADP/ATP, AMP/ATP, LKB1 activity, and CaMMKβ expression. From in vitro cell culture experiments, we found that AMPK activation of high-glucose conditions promoted cell apoptosis. Inhibition of AMPK had no obvious effect on apoptosis at the early stage with high glucose, but the inhibitory effect was significant at the late stage with high glucose. AMPK can regulate both mitochondrial metabolism and glycolysis pathways under high-glucose conditions. During the early stage with high glucose, AMPK was the main promotion factor of the mitochondrial metabolism pathway, but did not increase the ATP production, AMPK also promoted the glycolysis pathway. During the late stage with high glucose, AMPK was a major inhibitor of the mitochondrial pathway, and still played a role in promoting the glycolytic pathway, which acted as the main regulator. Apoptosis and energy metabolism disorders were present in gastric smooth muscle cells during the occurrence of DGP. Under high-glucose condition, AMPK was activated, which can promote apoptosis, change the energetic metabolism pathway of cells, inhibit mitochondrial energy metabolism, and promote glycolysis.
10.1007/s12013-019-00870-9
Opioid Use and Potency Are Associated With Clinical Features, Quality of Life, and Use of Resources in Patients With Gastroparesis.
Hasler William L,Wilson Laura A,Nguyen Linda A,Snape William J,Abell Thomas L,Koch Kenneth L,McCallum Richard W,Pasricha Pankaj J,Sarosiek Irene,Farrugia Gianrico,Grover Madhusudan,Lee Linda A,Miriel Laura,Tonascia James,Hamilton Frank A,Parkman Henry P,
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
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.
10.1016/j.cgh.2018.10.013
Cannabinoid Use in Patients With Gastroparesis and Related Disorders: Prevalence and Benefit.
Jehangir Asad,Parkman Henry P
The American journal of gastroenterology
OBJECTIVES:Gastroparesis (Gp) can be a challenging disorder to manage due to the paucity of treatment options. We do not know how frequently patients with Gp symptoms resort to cannabinoids to address their symptoms. This study (i) determines the prevalence of cannabinoid use in patients with Gp symptoms, (ii) describes the patients with Gp symptoms using cannabinoids, and (iii) assesses the patients' perceived benefit of cannabinoids for Gp symptoms. METHODS:Consecutive outpatients with symptoms suggestive of Gp seen on follow-up at our academic center from June 2018 to September 2018 filled out questionnaires on their symptoms and the current treatments. RESULTS:Of 197 patients, nearly half (n = 92, 46.7%) reported current (35.5%) or past (11.2%) use of cannabinoids, including tetrahydrocannabinol (n = 63), dronabinol (n = 36), and/or cannabidiol (n = 16). Of these, most perceived improvement in Gp symptoms from cannabinoids (93.5% with tetrahydrocannabinol, 81.3% with cannabidiol, and 47.2% with dronabinol). Cannabinoids were used most commonly via smoking (n = 46). Patients taking cannabinoids were younger (41.0 ± 15.4 vs 48.0 ± 15.9 years; P < 0.01) and had a higher Gastroparesis Cardinal Symptom Index total score (3.4 ± 1.0 vs 2.8 ± 1.3; P < 0.01) compared with patients with no history of cannabinoid use. CONCLUSIONS:A third of patients with Gp symptoms actively use cannabinoids for their chronic symptoms. Most of these patients perceive improvement in their symptoms with cannabinoids. Patients taking cannabinoids were younger and more symptomatic than those not taking cannabinoids. Further studies on the efficacy and safety of cannabinoids in Gp will be useful.
10.14309/ajg.0000000000000181
Therapeutic strategies in gastroparesis: Results of stepwise approach with diet and prokinetics, Gastric Rest, and PEG-J: A retrospective analysis.
Strijbos Denise,Keszthelyi Daniel,Smeets Fabiënne G M,Kruimel Joanna,Gilissen Lennard P L,de Ridder Rogier,Conchillo José M,Masclee Ad A M
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:Gastroparesis is characterized by abnormal gastric motor function with delayed gastric emptying in the absence of mechanical obstruction. In our tertiary referral center, patients are treated with a stepwise approach, starting with dietary advice and prokinetics, followed by three months of nasoduodenal tube feeding with "gastric rest." When not successful, a percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) for long-term enteral feeding is placed. AIM:To evaluate the effect of this stepwise approach on weight and symptoms. METHODS:Analyses of data of all referred gastroparesis patients between 2008 and 2016. KEY RESULTS:A total of 86 patients (71% female, 20-87 years [mean 55.8 years]) were analyzed of whom 50 (58%) had adequate symptom responses to diet and prokinetics. The remaining 36 (decompensated gastroparesis) were treated with three months gastric rest. Symptom response rate was 47% (17/36). Significant weight gain was seen in all patients, independent of symptom response. In the remaining 19 symptom non-responders, the enteral feeding was continued through PEG-J. Treatment was effective (symptoms) in 37%, with significant weight gain in all. In 84% of patients, the PEG-J is still in use (mean duration 962 days). CONCLUSIONS AND INFERENCES:Following a stepwise treatment approach in gastroparesis, adequate symptom response was reached in 86% of all patients. Weight gain was achieved in all patients, independent of symptom response. Diet and prokinetics were effective with regard to symptoms in 58%, temporary gastric rest in 47%, and PEG-J as third step in 37% of patients.
10.1111/nmo.13588
Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis.
Herring B Paul,Chen Meng,Mihaylov Plamen,Hoggatt April M,Gupta Anita,Nakeeb Attila,Choi Jennifer N,Wo John M
BMC medical genomics
BACKGROUND:Gastric emptying is impaired in patients with gastroparesis whereas it is either unchanged or accelerated in obese individuals. The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in idiopathic gastroparesis and obesity. METHODS:Quantitative real time RT-PCR and whole transcriptome sequencing were used to compare the transcriptomes of lean individuals, obese individuals and either lean or obese individuals with idiopathic gastroparesis. RESULTS:Obesity leads to an increase in mRNAs associated with muscle contractility whereas idiopathic gastroparesis leads to a decrease in mRNAs associated with PDGF BB signaling. Both obesity and idiopathic gastroparesis were also associated with similar alterations in pathways associated with inflammation. CONCLUSIONS:Our findings show that obesity and idiopathic gastroparesis result in overlapping but distinct changes in the gastric muscularis transcriptome. Increased expression of mRNAs encoding smooth muscle contractile proteins may be contributing to the increased gastric motility observed in obese subjects, whereas decreased PDGF BB signaling may be contributing to the impaired motility seen in subjects with idiopathic gastroparesis.
10.1186/s12920-019-0550-3
Ethnic, Racial, and Sex Differences in Etiology, Symptoms, Treatment, and Symptom Outcomes of Patients With Gastroparesis.
Parkman Henry P,Yamada Goro,Van Natta Mark L,Yates Katherine,Hasler William L,Sarosiek Irene,Grover Madhusudan,Schey Ron,Abell Thomas L,Koch Kenneth L,Kuo Braden,Clarke John,Farrugia Gianrico,Nguyen Linda,Snape William J,Miriel Laura,Tonascia James,Hamilton Frank,Pasricha Pankaj J,McCallum Richard W
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
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.
10.1016/j.cgh.2018.10.050
Gastroparesis and Dumping Syndrome: Current Concepts and Management.
Vavricka Stephan R,Greuter Thomas
Journal of clinical medicine
Gastroparesis and dumping syndrome both evolve from a disturbed gastric emptying mechanism. Although gastroparesis results from delayed gastric emptying and dumping syndrome from accelerated emptying of the stomach, the two entities share several similarities among which are an underestimated prevalence, considerable impairment of quality of life, the need for a multidisciplinary team setting, and a step-up treatment approach. In the following review, we will present an overview of the most important clinical aspects of gastroparesis and dumping syndrome including epidemiology, pathophysiology, presentation, and diagnostics. Finally, we highlight promising therapeutic options that might be available in the future.
10.3390/jcm8081127
Fluctuating International Normalized Ratio in Patients Compliant on Warfarin: Could Gastroparesis Be the Cause?
Zia Mudassar,Pirani Nurry
Cureus
Warfarin is the drug of choice to achieve therapeutic anticoagulation in patients with mechanical heart valves. Factors that interfere with the reliable absorption of warfarin may result in difficult to control international normalized ratio (INR) and can cause significant bleeding complications due to supra-therapeutic INR and thromboembolism from sub-therapeutic INR. The patient's non-compliance is an important factor leading to difficult to control INR but there are additional factors that should be considered in difficult cases when dietary and medication compliance are observed. Gastroparesis is one such predominant and overlooked factor. A 58-year-old African American female with a history of mechanical mitral valve who was on anticoagulation with warfarin was admitted multiple times, with frequent episodes of significant bleeding episodes and fluctuating INR between sub- and supra-therapeutic readings despite being on a relatively stable dose of Coumadin. She was eventually diagnosed with severe gastroparesis, which was the cause of her fluctuating INR. A case can be made to consider gastric motility testing in such patients, where achieving a therapeutic range for anticoagulation is difficult in the setting of medication and dietary compliance.
10.7759/cureus.5080
Abdominal Pain in Patients with Gastroparesis: Associations with Gastroparesis Symptoms, Etiology of Gastroparesis, Gastric Emptying, Somatization, and Quality of Life.
Parkman Henry P,Wilson Laura A,Hasler William L,McCallum Richard W,Sarosiek Irene,Koch Kenneth L,Abell Thomas L,Schey Ron,Kuo Braden,Snape William J,Nguyen Linda,Farrugia Gianrico,Grover Mandhusudan,Clarke John,Miriel Laura,Tonascia James,Hamilton Frank,Pasricha Pankaj J
Digestive diseases and sciences
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.
10.1007/s10620-019-05522-9
Metoclopramide for the treatment of diabetic gastroparesis.
Shakhatreh Mohammed,Jehangir Asad,Malik Zubair,Parkman Henry P
Expert review of gastroenterology & hepatology
: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of gastroparesis. Management of diabetic gastroparesis involves lifestyle modifications, glycemic control, pharmacological drugs, and for refractory cases surgical treatments. Metoclopramide remains the only drug approved by the Food and Drug Administration for diabetic gastroparesis. The aim of this article is to provide a concise review of the pharmacology, clinical efficacy and tolerability of metoclopramide. : We searched PubMed using the key words 'metoclopramide', 'diabetic gastroparesis', and 'gastric emptying'. The relevant articles and their bibliography were reviewed. Metoclopramide acts on several different receptors; primarily as a dopamine receptor antagonist, both peripherally improving gastric emptying, and centrally resulting in an anti-emetic effect. Metoclopramide side effects, mostly related to its ability to cross the blood-brain barrier, include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible. : Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD. However, gastroparesis patients experience chronic symptoms often requiring prolonged treatments. Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profile.
10.1080/17474124.2019.1645594
Prucalopride in Gastroparesis: A Randomized Placebo-Controlled Crossover Study.
Carbone Florencia,Van den Houte Karen,Clevers Egbert,Andrews Christopher N,Papathanasopoulos Athanassos,Holvoet Lieselot,Van Oudenhove Lukas,Caenepeel Philip,Arts Joris,Vanuytsel Tim,Tack Jan
The American journal of gastroenterology
OBJECTIVES:Prokinetics are considered the preferred treatment option for gastroparesis, but evidence of their efficacy is scarce. Prucalopride, a selective 5-hydroxytryptamine 4 receptor agonist used in the treatment of constipation, is able to enhance the gastric emptying rate. In a double-blind, randomized, placebo-controlled crossover study, we evaluated the efficacy of prucalopride to improve the gastric emptying rate and symptoms in patients with gastroparesis. METHODS:Thirty-four patients with gastroparesis (28 idiopathic, 7 men, mean age 42 ± 13 years) were evaluated in a double-blind crossover trial of 4-week treatment periods with placebo or prucalopride 2 mg q.d., separated by 2 weeks of washout. The primary end point was the change in symptom severity, assessed by the Gastroparesis Cardinal Symptom Index; secondary end points comprised the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index, the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life, and daily diaries, and the gastric emptying rate was assessed by the C-octanoic acid breath test. RESULTS:Three patients were lost to follow-up. One serious adverse event occurred (small bowel volvulus in the prucalopride group), and 3 patients dropped out because of adverse events of nausea and headache (all prucalopride). For the entire patient group, compared with placebo, prucalopride significantly improved the total Gastroparesis Cardinal Symptom Index (1.65 ± 0.19 vs 2.28 ± 0.20, P < 0.0001) and the subscales of fullness/satiety, nausea/vomiting, and bloating/distention. Prucalopride significantly improved the overall Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (1.15 ± 0.16 vs 1.44 ± 0.16, P < 0.05) and the domains of clothing and diet. The gastric half emptying time was significantly enhanced by prucalopride compared with placebo and baseline (98 ± 10 vs 143 ± 11 and 126 ± 13 minutes, P = 0.005 and <0.001, respectively). These significant improvements were also found when considering only the idiopathic gastroparesis subgroup. DISCUSSION:In a cohort of patients with predominantly idiopathic gastroparesis, 4 weeks of prucalopride treatment significantly improved symptoms and quality of life and enhanced gastric emptying compared with placebo.
10.14309/ajg.0000000000000304
Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited.
Al-Saffar Ahmad,Lennernäs Hans,Hellström Per M
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:Metoclopramide is primarily a dopamine receptor antagonist, with 5HT receptor antagonist and 5HT receptor agonist activity, and used as an antiemetic and gastroprokinetic since almost 50 years. Regulatory authorities issued restrictions and recommendations regarding long-term use of the drug at oral doses exceeding 10 mg 3-4 times daily because of the risk for development of tardive dyskinesia. The aim of our study was to review mechanism(s) of action and pharmacokinetic-pharmacodynamic properties of metoclopramide, as well as the risk of metoclopramide-induced tardive dyskinesia, factors that may change drug exposure in humans, and to summarize the clinical context for appropriate use of the drug. METHODS:A PubMed, Google Scholar, and Cross Reference search was done using the key words and combined searches: drug-drug interaction, gastroparesis, metoclopramide, natural history, pharmacokinetics, pharmacodynamics, drug-drug interaction, outcome, risk factors, tardive dyskinesia. KEY RESULTS:Data show that the risk of tardive dyskinesia from metoclopramide is low, in the range of 0.1% per 1000 patient years. This is far below a previously estimated 1%-10% risk suggested in treatment guidelines by regulatory authorities. High-risk groups are elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy, which reduces the threshold for neurological complications. CONCLUSIONS & INFERENCES:The risk of tardive dyskinesia due to metoclopramide is far below approximated numbers in treatment guidelines. This risk and the influence of known risk factors should be considered when starting a course of metoclopramide for treatment of gastroparesis.
10.1111/nmo.13617
Symptoms Suggestive of Gastroparesis in a Community-Based Cohort of European Americans and African Americans with Type 2 Diabetes Mellitus.
Digestive diseases and sciences
BACKGROUND:Although gastroparesis is seen in patients with type 2 diabetes mellitus (T2DM), the prevalence of symptoms suggestive of gastroparesis in patients with T2DM is unknown, particularly among African Americans. AIMS:To determine the prevalence of symptoms associated with gastroparesis in a large community-based population of European Americans and African Americans with T2DM. METHODS:Individuals with T2DM in the Diabetes Heart Study were asked to complete the gastroparesis cardinal symptom index (GCSI) and other GI-related questionnaires. GCSI total score ≥ 18 represented moderate or worse symptoms suggestive of gastroparesis. RESULTS:A total of 1253 participants (700 female, 553 male) completed the GCSI: 750 were European American and 503 African American. GCSI scores ≥ 18 were recorded in 72 participants: 38 (5%) of European Americans and 34 (7%) of African Americans. The average GCSI was 24.1 in European Americans and 24.6 in African Americans, indicating moderate to severe symptoms. Compared to European Americans with GCSI scores ≥ 18, African Americans were younger (59.4 vs. 53.3 years, p = 0.004), had earlier onset of T2DM (46.3 vs. 40.1 years, p = 0.01), higher HbA1c (7.6 vs. 9.1, p = 0.0009), underwent fewer upper endoscopies (55.3% vs. 26.5%, p = 0.02), and had more anxiety and depression (p < 0.001). CONCLUSIONS:Moderate or greater symptoms suggestive of gastroparesis are present in 5-7% of European and African American patients with T2DM in community-based populations. Symptoms suggestive of gastroparesis may be underappreciated in patients with T2DM and account for upper gastrointestinal symptoms, unexplained glycemic control issues, and decreased quality of life.
10.1007/s10620-019-05974-z
Childhood gastroparesis is a unique entity in need of further investigation.
Febo-Rodriguez Liz,Chumpitazi Bruno P,Shulman Robert J
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:Despite increasing knowledge regarding gastroparesis (GP) in adults, little is known regarding the incidence, prevalence, and natural history of childhood GP. Exacerbating the knowledge gap in pediatric GP is both the lack of normative data for gastric emptying scintigraphy in children and lack of GP-specific pediatric reported outcome measures. PURPOSE:The aim of this article was to review the available literature on pediatric GP and identify similarities and differences with studies in adults. We performed a comprehensive search in MEDLINE and Google Scholar from inception to April 2019 for articles published in English using the following combination of keywords: gastroparesis, pediatric gastroparesis, outcomes, metoclopramide, erythromycin, domperidone, cisapride, and gastric neurostimulator. The limited available pediatric data, often retrospective, suggest marked differences between adult and pediatric GP in several aspects including etiology, concomitant co-morbidities (eg, psychiatric disorders), clinical symptom presentation, diagnostic evaluation, response to therapies, and clinical outcome. Further research in pediatric GP is needed and holds the promise to further elucidate the mechanisms of this disorder in children and lead to pediatric-focused therapies.
10.1111/nmo.13699
Psychological controversies in gastroparesis: A systematic review.
Woodhouse Sally,Hebbard Geoff,Knowles Simon R
World journal of gastroenterology
AIM:To systematically review literature addressing three key psychologically-oriented controversies associated with gastroparesis. METHODS:A comprehensive search of PubMed, CINAHL, and PsycINFO databases was performed to identify literature addressing the relationship between gastroparesis and psychological factors. Two researchers independently screened all references. Inclusion criteria were: an adult sample of gastroparesis patients, a quantitative methodology, and at least one of the following: (1) evaluation of the prevalence of psychopathology; (2) an outcome measure of anxiety, depression, or quality of life; and (3) evidence of a psychological intervention. Case studies, review articles, and publications in languages other than English were excluded from the current review. RESULTS:Prevalence of psychopathology was evaluated by three studies ( = 378), which found that combined anxiety/depression was present in 24% of the gastroparesis cohort, severe anxiety in 12.4%, depression in 21.8%-23%, and somatization in 50%. Level of anxiety and depression was included as an outcome measure in six studies ( = 1408), and while limited research made it difficult to determine the level of anxiety and depression in the cohort, a clear positive relationship with gastroparesis symptom severity was evident. Quality of life was included as an outcome measure in 11 studies ( = 2076), with gastroparesis patients reporting lower quality of life than population norms, and a negative relationship between quality of life and symptom severity. One study assessed the use of a psychological intervention for gastroparesis patients ( = 120) and found that depression and gastric function were improved in patients who received psychological intervention, however the study had considerable methodological limitations. CONCLUSION:Gastroparesis is associated with significant psychological distress and poor quality of life. Recommendations for future studies and the development of psychological interventions are provided.
10.3748/wjg.v23.i7.1298
Assessment of the Prevalence of Diabetic Gastroparesis and Validation of Gastric Emptying Scintigraphy for Diagnosis.
Alipour Zeinab,Khatib Foad,Tabib Seyed Masoud,Javadi Hamid,Jafari Esmail,Aghaghazvini Leila,Mahmoud-Pashazadeh Ali,Nabipour Iraj,Assadi Majid
Molecular imaging and radionuclide therapy
OBJECTIVE:Gastroparesis is defined as delayed gastric emptying and is a common medical condition in diabetic patients. Scintigraphy is commonly used as a standard diagnostic procedure for the quantitative assessment of gastroparesis. The aims of this study were to determine an optimum imaging time for the diagnosis of gastroparesis, to assess the prevalence of gastroparesis, to evaluate the correlation between endoscopy and scintigraphy findings as well as the correlation between gastric emptying with patient genders, blood glucose concentration, and functional dyspepsia. METHODS:Gastric emptying was assessed in 50 diabetic patients with a mean age of 50.16 years. For evaluation of gastric emptying, a test meal containing 2 pieces of toast, 120 cc non-labeled water and fried egg labeled with 1 mCi of Tc was given to each patient. The scintigraphy was performed immediately after ingestion and was repeated at 1, 1.5, 2 and 4 hours after ingestion. In some patients, an additional 90-minute dynamic scan was also acquired. RESULTS:The prevalence of gastroparesis in this study population was determined as 64%. Also, the results of this study revealed that a 4-hour scan after ingestion is more relevant than a 90-minute dynamic scan for the evaluation of delayed gastric emptying. There was no statistically significant difference between 1-hour and 2-hour scans, 1-hour and 90-minute scans, 2-hour and 90-minute scans, 2-hour and 4-hour scans. Likewise there was no significant correlation between blood glucose levels, gender and calculated values of gastric emptying time in all groups. CONCLUSION:According to our findings, it can be suggested that the prevalence of gastroparesis is higher than that mentioned in some previous studies. Also, this study indicates that a gastric emptying scintigraphy at 2 and 4 hours after meal ingestion might provide the anticipated clinical information in diabetic patients with dyspepsia without other evident reasons.
10.4274/mirt.61587
Pyloric Therapies for Gastroparesis.
Ahuja Nitin K,Clarke John O
Current treatment options in gastroenterology
OPINION STATEMENT:Gastroparesis is a syndrome that can be difficult to treat effectively and likely represents the common clinical presentation of multiple underlying mechanisms. One of these presumed mechanisms involves pyloric dysfunction, tied perhaps to spasm or fibrosis, manifesting as functional gastric outlet obstruction. Various diagnostic modalities have been used to better characterize this hypothesized abnormality, including most recently antroduodenal manometry and impedance planimetry. A variety of therapeutic interventions specific to the pylorus have also been proposed in the last several years, including intrapyloric injections of botulinum toxin, transpyloric stenting, surgical pyloroplasty, and endoscopic pyloromyotomy. The clinical application of these maneuvers has been mostly empiric thus far, but efforts are ongoing to identify the subset of patients whose physiology best positions them to benefit from such therapy. Early results for many of these interventions have been promising and will serve as the basis for larger and more systematic research frameworks moving forward.
10.1007/s11938-017-0124-4
Investigational drug therapies for the treatment of gastroparesis.
Sanger Gareth J,Pasricha Pankaj Jay
Expert opinion on investigational drugs
INTRODUCTION:Gastroparesis is defined by nausea, vomiting, pain, early satiety and bloating, and characterized by delayed gastric emptying without obvious structural abnormalities. Metoclopramide is widely used, increasing gastric emptying and inhibiting nausea and vomiting. Other drugs are available in certain countries and some are used 'off-label' because they increase gastric emptying or inhibit emesis. However, correlation between gastroparesis symptoms and rates of gastric emptying is poor. For anti-emetic drugs, dose-ranging and Phase III trials in gastroparesis are lacking. Areas covered: Gastric motility may still be disordered, leading to nausea, even though gastric emptying is unchanged. One hypothesis is that interstitial cells of Cajal (ICC) are damaged by diabetes leading to gastric dysrhythmia and nausea. Novel approaches to treatment of nausea also include the use of ghrelin receptor agonists, highlighting a link between appetite and nausea. Expert opinion: There is an urgent need to diversify away from historical drug targets. In particular, there is a need to control nausea by regulating ICC functions and/or by facilitating appetite via ghrelin receptor agonists. It is also important to note that different upper gastrointestinal disorders (gastroparesis, chronic unexplained nausea and vomiting, functional dyspepsia) are difficult to distinguish apart, suggesting wider therapeutic opportunity.
10.1080/13543784.2017.1288214
Mirtazapine for symptom control in refractory gastroparesis.
Malamood Mark,Roberts Aaron,Kataria Rahul,Parkman Henry P,Schey Ron
Drug design, development and therapy
INTRODUCTION:Gastroparesis symptoms can be severe and debilitating. Many patients do not respond to currently available treatments. Mirtazapine has been shown in case reports to reduce symptoms in gastroparesis. AIM:To assess the efficacy and safety of mirtazapine in gastroparetic patients. METHODS:Adults with gastroparesis and poorly controlled symptoms were eligible. Participants were prescribed mirtazapine 15 mg PO qhs. Questionnaires containing the gastrointestinal cardinal symptom index (GCSI) and the clinical patient grading assessment scale (CPGAS) were completed by patients' pretreatment, at 2 weeks, and at 4 weeks. Primary end point was nausea and vomiting response to mirtazapine using the GCSI. Secondary end point was nausea and vomiting severity assessment using the CPGAS. -values were calculated using the paired two-tailed Student's -test. Intention to treat analysis was used. RESULTS:A total of 30 patients aged 19-86 years were enrolled. Of those, 24 patients (80%) completed 4 weeks of therapy. There were statistically significant improvements in nausea, vomiting, retching, and perceived loss of appetite at 2 and 4 weeks (all -values <0.05) compared with pretreatment. There was a statistically significant improvement in the CPGAS score at week 2 (=0.003) and week 4 (<0.001). Of the total patients, 14 (46.7%) experienced adverse effects from mirtazapine and due to this, 6 patients stopped therapy. CONCLUSION:Mirtazapine significantly improved both nausea and vomiting in gastroparetics after 2 and 4 weeks of treatment. Side effects led to treatment self-cessation in a fifth of patients. From these data, we conclude that mirtazapine improves nausea and vomiting, among other symptoms, in patients with gastroparesis and might be useful in select patients.
10.2147/DDDT.S125743
The Association Between Fasting C-peptide and Gastrointestinal Symptoms of Gastroparesis in Type 2 Diabetic Patients.
Huang Yun,Zhang Honghong,Zhang Minxia,Li Wenya,Wang Jinhua,Hu Ji
Journal of neurogastroenterology and motility
BACKGROUND/AIMS:The relationship between C-peptide levels and gastrointestinal (GI) symptoms in type 2 diabetic patients is not clear. The purpose of this study is to examine the association between fasting C-peptide and GI symptoms of gastroparesis in type 2 diabetic patients. METHODS:We recruited 333 type 2 diabetic patients into the present study. All patients filled out questionnaires of gastroparesis cardinal symptom index (GCSI) to evaluate GI symptoms. Hospital anxiety and depression scale were adopted to define anxiety and depression. Patients with GCSI scores ≥ 1.9 were regarded as having symptoms of gastroparesis. RESULTS:In our study, 71 (21.3%) type 2 diabetic patients had GCSI scores ≥ 1.9. In comparison to patients with scores < 1.9, those with scores ≥ 1.9 had significantly lower fasting c-peptide levels (1.49 ng/mL vs 1.94 ng/mL, < 0.001), higher prevalence of depression (40.9% vs 18.3%, < 0.001) and anxiety (28.2% vs 13.0%, = 0.002). Multivariate logistic regression revealed that fasting C-peptide was still significantly associated with symptoms of gastroparesis (odds ratio, 0.67; 95% confidence intervals, 0.48-0.94; = 0.021), even after adjustments for age, sex, body mass index, HbA1c, current smoking and drinking status, anxiety, and depression. Furthermore, linear regressions showed that fasting C-peptide was independently and negatively related to GCSI scores (standardized regression coefficient, -0.29; < 0.001) in patients with at least one GI symptom. CONCLUSION:GI symptoms of diabetic gastroparesis affect approximately 20% of type 2 diabetes patients and are associated with lower fasting C-peptide levels independent of depression and anxiety status.
10.5056/jnm16091
Central and Peripheral Effects of Transcutaneous Acupuncture Treatment for Nausea in Patients with Diabetic Gastroparesis.
Sarosiek Irene,Song Gengqing,Sun Yan,Sandoval Hugo,Sands Stephen,Chen Jiande,McCallum Richard W
Journal of neurogastroenterology and motility
BACKGROUND/AIMS:Nausea, an unpleasant symptom of diabetic gastroparesis (DMGP), has been reported to be alleviated by needleless transcutaneous electrical acupuncture (TEA). Our study was designed to utilize electroencephalography (EEG) and electrogastrography (EGG) recordings to investigate the central and peripheral responses of TEA in the treatment of nausea in DMGP patients. METHODS:Eleven DMGP subjects underwent simultaneous EEG and EGG testing while grading the severity of nausea following 30-minute intervals of: (1) baseline, (2) visual stimulation (VS) to provoke more nausea, (3) active VS together with TEA, and (4) TEA alone, and a final 15-minute recording without any intervention. RESULTS:The nausea score was increased to 5.9 ± 1.5 with VS ( < 0.05, vs 3.5 ± 1.0 at baseline), then reduced to 3.5 ± 1.2 with VS plus TEA, and to 2.5 ± 1.3 with TEA alone, while it continued at a score of 2.9 ± 1.0 post TEA (all significant, < 0.05, vs VS without TEA). The mean percentage of normal gastric slow waves was decreased to 60.0 ± 5.7% with VS ( < 0.05, vs 66.6 ± 4.5% at baseline), then improved to 69.2 ± 4.8% with VS plus TEA, and maintained at 70 ± 3.6% with TEA alone. During initial VS, EEG signals showed right inferior frontal activity as the prominent finding, but during VS with TEA, left inferior frontal activity predominated. CONCLUSIONS:In DMGP, TEA improves gastric dysrhythmia and ameliorates nausea. TEA treatment of nausea provoked by VS resulted in a change of dominance from right to left inferior frontal lobe activity. These data provide new understandings of peripheral and central mechanisms for nausea, and potential future directions for DMGP treatment approaches.
10.5056/jnm16097
Electroacupuncture combined with mosapride alleviates symptoms in diabetic patients with gastroparesis.
Pan Wenping,Wang Zhankui,Tian Feilong,Yan Mingxian,Lu Yan
Experimental and therapeutic medicine
The present study compared the clinical effectiveness of electroacupuncture (EA), monotherapy and combination therapy involving the administration of EA and mosapride in diabetic patients with severe or mild symptoms suggestive of gastroparesis. A total of 56 patients with type 2 diabetes who had symptoms suggestive of gastroparesis for >3 months were divided into two groups according to the Gastroparesis Cardinal Symptom Index (GCSI) score, including 33 in the mild group (GCSI score <3.5) and 23 in the severe group (GCSI score ≥3.5). Initially, all patients received EA monotherapy for 14 days. An effective response was defined as a reduction of the overall baseline GCSI score by >25% after treatment. The non-responding patients then received a combination treatment with EA and mosapride. Gastric emptying was assessed by the C-octanoic acid breath test at the beginning and end of each treatment session. Two patients in the severe group dropped out of the study during the initial treatment session. The results revealed that 34 early-responding patients (30 from the mild group and 4 from the severe group) treated with EA monotherapy, and 20 non-early-responding patients receiving combination therapy with EA and mosapride showed clinically significant improvements. Analysis of data from the mild subgroup demonstrated that EA treatment specifically improved symptoms of nausea, vomiting, stomach fullness, excessive fullness and bloating. There was no statistically significant difference in the gastric half-emptying time among patients prior to and after EA monotherapy. These preliminary results suggested that EA may be an option for improving mild symptoms in patients with diabetic gastroparesis, whereas combination therapy involving EA and pharmaceutics is required in patients with severe symptoms.
10.3892/etm.2017.4139
Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum.
Grover M,Bernard C E,Pasricha P J,Parkman H P,Gibbons S J,Tonascia J,Koch K L,McCallum R W,Sarosiek I,Hasler W L,Nguyen L A B,Abell T L,Snape W J,Kendrick M L,Kellogg T A,McKenzie T J,Hamilton F A,Farrugia G,
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
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.
10.1111/nmo.13018
Taste and Smell Disturbances in Patients with Gastroparesis and Gastroesophageal Reflux Disease.
Kabadi Alisha,Saadi Mohammed,Schey Ron,Parkman Henry P
Journal of neurogastroenterology and motility
BACKGROUND/AIMS:Patients with gastroparesis and gastroesophageal reflux disease (GERD) often report decreased enjoyment when eating. Some patients remark that food does not smell or taste the same. To determine if taste and/or smell disturbances are present in patients with gastroparesis and/or GERD and relate these to gastrointestinal symptom severity. METHODS:Patients with gastroparesis and/or GERD completed questionnaires evaluating taste and smell (Taste and Smell Survey [TSS]), Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), and Demographics. TSS questioned the nature of taste/smell changes and the impact on quality of life. PAGI-SYM was used to calculate Gastroparesis Cardinal Symptom Index (GCSI) and Heartburn and Regurgitation Score (HB/RG). RESULTS:Seventy-six subjects were enrolled: healthy controls (n = 13), gastroparesis alone (n = 30), GERD alone (n = 10), and both gastroparesis and GERD (n = 23). Taste and smell disturbances were higher in patients with gastroparesis, GERD, and both gastroparesis and GERD compared to healthy controls. Taste and smell abnormalities were significantly correlated ( = 0.530, < 0.001). Taste score was strongly correlated with HB/RG ( = 0.637, < 0.001) and with GCSI ( = 0.536, < 0.001). Smell score was also strongly correlated to HB/RG ( = 0.513, < 0.001) and GCSI ( = 0.495, < 0.001). CONCLUSIONS:Taste and smell abnormalities are prominent in gastroparesis and GERD patients. Abnormalities in taste and smell are significantly correlated with both gastroparesis and GERD symptom severity. Awareness of this high prevalence of taste and smell dysfunction among patients with gastroparesis and GERD may help to better understand the food intolerances these patients often have.
10.5056/jnm16132
Gastric neuromuscular histology in patients with refractory gastroparesis: Relationships to etiology, gastric emptying, and response to gastric electric stimulation.
Heckert J,Thomas R M,Parkman H P
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
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.
10.1111/nmo.13068
Patients with symptoms of delayed gastric emptying have a high prevalence of oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis.
Triadafilopoulos George,Nguyen Linda,Clarke John O
BMJ open gastroenterology
BACKGROUND:Patients with symptoms suggestive of gastroparesis exhibit several symptoms, such as epigastric pain, postprandial fullness, bloating and regurgitation. It is uncertain if such symptoms reflect underlying oesophageal motor disorder. AIMS:To examine whether patients with epigastric pain and postprandial distress syndrome suggestive of functional dyspepsia and/or gastroparesis also have concomitant oesophageal motility abnormalities and, if so, whether there are any associations between these disturbances. METHODS:In this retrospective cohort study, consecutive patients with functional gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring using standard protocols. RESULTS:We studied 61 patients with various functional upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring. Forty-four patients exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders were found in 68% and 42% of patients with or without scintigraphic evidence of gastroparesis respectively, suggesting of overlapping gastric and oesophageal neuromuscular disorder. Forty-three per cent of patients with gastroparesis had abnormal oesophageal acid exposure with mean % pH <4.0 of 7.5 in contrast to 38% of those symptomatic controls with normal gastric emptying, with mean %pH <4.0 of 5.4 (NS). Symptoms of epigastric pain, heartburn/regurgitation, bloating, nausea, vomiting, dysphagia, belching and weight loss could not distinguish patients with or without gastroparesis, although weight loss was significantly more prevalent and severe (p<0.002) in patients with gastroparesis. There was no relationship between oesophageal symptoms and motor or pH abnormalities in either groups. CONCLUSIONS:Irrespective of gastric emptying delay by scintigraphy, patients with symptoms suggestive of gastric neuromuscular dysfunction have a high prevalence of oesophageal motor disorder and pathological oesophageal acid exposure that may contribute to their symptoms and may require therapy. High-resolution oesophageal manometry and pH monitoring are non-invasive and potentially useful in the assessment and management of these patients.
10.1136/bmjgast-2017-000169
Gastroparesis Updates on Pathogenesis and Management.
Liu Nanlong,Abell Thomas
Gut and liver
Gastroparesis (Gp) is a chronic disease that presents with clinical symptoms of early satiety, bloating, nausea, vomiting, and abdominal pain. Along with these symptoms, an objective finding of delayed gastric emptying, along with a documented absence of gastric outlet obstruction, are required for diagnosis. This article focuses on updates in the pathogenesis and management of Gp. Recent studies on full thickness biopsies of Gp patients have shed light on the complex interactions of the central, autonomic, and enteric nervous systems, which all play key roles in maintaining normal gut motility. The management of Gp has evolved beyond prokinetics and antiemetics with the use of gastric electrical stimulators (GES). In addition, this review aims to introduce the concept of gastroparesis-like syndrome (GLS). GLS helps groups of patients who have the cardinal symptoms of Gp but have a normal or rapid emptying test. Recent tests have shown that patients with Gp and GLS have similar pathophysiology, benefit greatly from GES placement, and likely should be treated in a similar manner.
10.5009/gnl16336
Vitamin C Improves Gastroparesis in Diabetic Rats: Effects on Gastric Contractile Responses and Oxidative Stress.
Da Silva Luisa Mota,da Silva Rita de Cássia Melo Vilhena de Andrade Fonseca,Maria-Ferreira Daniele,Beltrame Olair Carlos,da Silva-Santos José Eduardo,Werner Maria Fernanda de Paula
Digestive diseases and sciences
BACKGROUND:Diabetic gastroparesis is a common complication of diabetes mellitus, which mainly affects women. Previous studies have demonstrated that oxidative stress is involved in its onset and development. AIMS:This study evaluated the role of vitamin C on diabetes-associated gastric dysmotility. METHODS:Female rats with streptozotocin-induced diabetes were treated with vehicle (water, 1 mL/kg, p.o.), vitamin C (300 mg/kg/day, p.o.), or insulin (6 IU/day, s.c.). Gastric emptying, in vitro gastric contractility, and biochemistry parameters were analyzed at the end of the treatment (i.e. 8 weeks after the diabetes induction). RESULTS:Vitamin C reversed the delayed gastric emptying of diabetic rats to normal levels, and avoided the changes in the contractile responses to acetylcholine (0.1 nM-1 µM), but not to 5-hydroxytryptamine (0.1 nM-1 µM), in the pylorus and fundus from diabetic rats. Moreover, the contraction evoked by KCl (40 mM) in the fundus, but not in the pylorus, was intensely increased in diabetic rats treated with vitamin C. Notably, the vitamin C reestablished the reduced glutathione levels by 77% and decreased the reactive oxygen species content by 60% in the gastric tissue from diabetic rats. Despite the effects on gastric motility, vitamin C treatment did not change the fasting glycaemia or the glycated hemoglobin of diabetic rats. Unsurprisingly, insulin treatment normalized all parameters evaluated. CONCLUSIONS:Vitamin C exhibited a remarkable beneficial effect on gastric emptying dysfunction in diabetic rats, which was mediated by attenuation of oxidative stress and maintenance of the cholinergic contractile responses in fundus and pylorus.
10.1007/s10620-017-4632-9
Pathological Findings of the Antral and Pyloric Smooth Muscle in Patients with Gastroparesis-Like Syndrome Compared to Gastroparesis: Similarities and Differences.
Bashashati Mohammad,Moraveji Sharareh,Torabi Alireza,Sarosiek Irene,Davis Brian R,Diaz Jesus,McCallum Richard W
Digestive diseases and sciences
BACKGROUND:Gastroparesis (GP)-like syndrome presents with the symptoms of GP but without delayed gastric emptying (GE). Whether GP-like syndrome is part of a spectrum of GP is not clear. This study aimed to compare the histopathological features of antral and pyloric smooth muscle tissue in GP and GP-like syndrome. METHODS:Full-thickness antral and/or pyloric biopsies were obtained from 37 GP and 18 GP-like syndrome patients who underwent abdominal surgery to place a gastric electrical stimulator or jejunal feeding tube and/or pyloroplasty. The tissues were stained with H&E, C-Kit, and trichrome. Based on previous control data, an interstitial cells of Cajal (ICC) count of <10 per high power field in the antrum and/or pylorus was considered depletion. Baseline total symptom score (TSS) was recorded. RESULTS:Twenty-four GP and 7 GP-like patients had pyloric biopsies. Pyloric ICC loss was observed in 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients (p < 0.01). Fibrosis was detected in the pyloric tissue of 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients who had pyloric trichrome staining (p < 0.01). Seventeen out of 24 (70.8%) GP patients with pyloric biopsies had concomitant pyloric ICC loss and fibrosis, while only one GP-like patient had ICC loss and simultaneous pyloric fibrosis. GP patients had a greater TSS compared to GP-like patients. In GP patients, those with pyloric ICC loss had a greater TSS compared to those with normal ICC. GP patients with pyloric fibrosis had a higher TSS compared to those without pyloric fibrosis. CONCLUSIONS:Compared to GP-like patients, the pyloric histopathological findings of ICC loss and fibrosis are common in GP and predict a greater symptom score. These pathological findings might be considered as markers of "pyloric dysfunction" and explain delayed GE in GP.
10.1007/s10620-017-4629-4
Exploration of the psychosocial issues associated with gastroparesis: a qualitative investigation.
Woodhouse Sally,Hebbard Geoff,Knowles Simon R
Journal of clinical nursing
AIMS AND OBJECTIVES:To build on the understanding of how individuals experience gastroparesis, how gastroparesis impacts on their lives and how they adapt to living with gastroparesis. BACKGROUND:Gastroparesis is a neurogastroenterological disorder associated with increased psychological distress and reduced quality of life. Research shows that gastroparesis poses a significant burden across many facets of life; however, less is known about how individuals cope and adapt to living with the condition. DESIGN:The study employed an interpretive phenomenological approach with semistructured interviews and thematic analysis. METHODS:Ten gastroparesis patients were interviewed over the telephone (n = 8), Skype (n = 1) or face-to-face (n = 1). All interviews were audio-recorded and transcribed. RESULTS:Key themes identified: (1) frustration, (2) identity and (3) coping and adaptation. Gastroparesis patients experience significant frustration around their diagnostic journey, being misunderstood and the burden of living with the illness. Patients differed in how they identified with the illness, and this appeared to be associated with adaptation and whether they remained socially engaged. CONCLUSIONS:Gastroparesis is associated with significant frustration and burden; however, some patients adapt to living with the condition more effectively than others. Identity appears to play an important role in this relationship. Support aimed at fostering a health-focused and resilient identity may assist gastroparesis patients in adaptation. RELEVANCE TO CLINICAL PRACTICE:The findings of this study can help nurses and other healthcare professionals better understand the experience of living with gastroparesis and the factors that help patients best adapt to living with the condition. Nurses can help promote resilience in patients by discussing the importance of being health-focused rather than illness-focused. Nurses can also support patients by helping them problem-solve issues that may arise around social eating and remaining socially engaged.
10.1111/jocn.13725
Fluoroscopy-guided gastric peroral endoscopic pyloromyotomy (G-POEM): a more reliable and efficient method for treatment of refractory gastroparesis.
Xue H B,Fan H Z,Meng X M,Cristofaro S,Mekaroonkamol P,Dacha S,Li L Y,Fu X L,Zhan S H,Cai Q
Surgical endoscopy
INTRODUCTION:Prior studies show promising results of the gastric peroral endoscopic pyloromyotomy (G-POEM) procedure for treatment of refractory gastroparesis. One major technical challenge involved in this procedure is identifying the pyloric muscular ring (PMR). The aim of this study is to establish a reliable method for identification of the PMR during G-POEM. METHODS:Fluoroscopy-guided G-POEM was performed by placing an endoclip at the 9 to 11'o clock position at the pylorus for identification of PMR. Conventional G-POEM was performed by observation of blue colored mucosa at the pylorus area as an indirect marker for PMR. The degree of the PMR identification was graded into well identified, identified, and not identified based on the appearance of the PMR. Procedure times were accurately documented. Gastroparesis cardinal symptoms index and gastric emptying scintigraphy were evaluated before and after the procedure. RESULTS:Fourteen patients were studied, seven underwent fluoroscopy-guided G-POEM, and seven patients underwent conventional G-POEM. All procedures achieved technical success and no adverse events occurred. In the seven patients who underwent fluoroscopy-guided G-POEM, the PMR was well identified in four patients and identified in three patients. In the seven patients who underwent conventional G-POEM, the PMR was identified in four patients and not identified in three patients. The average time to complete the fluoroscopy-guided G-POEM was significantly shorter than that of the conventional G-POEM. CONCLUSIONS:Fluoroscopy-guided G-POEM by placement of an endoclip at the pylorus was a reliable and safe method to direct the orientation of the submucosal tunnel, to facilitate the location of the PMR, and to shorten the procedure time.
10.1007/s00464-017-5524-y
Higenamine inhibits apoptosis and maintains survival of gastric smooth muscle cells in diabetic gastroparesis rat model via activating the β2-AR/PI3K/AKT pathway.
An Xiaoxia,Long Chunli,Deng Xiaomin,Tang Aihua,Xie Junyan,Chen Li,Wang Zhengang
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). The numerous clinical symptoms of DGP and the great cost on the treatment of DGP seriously lowered the patients' life quality. However, the pathogenic mechanism of DGP is still elusive till now. In this study, we aimed to explore the effect of higenamine on the proliferation and apoptosis of gastric smooth muscle cells (SMCs) in DGP rat model. The DGP rat model was built by intraperitoneal injection of Streptozotocin (STZ) into male Sprague-Dawley (SD) rats. Compared with the healthy control group, the level of DGP indicator c-kit was strongly suppressed and the level of Gsα was largely elevated in the STZ-induced model group. By contrast, the addition of higenamine obviously counteracted the effect of STZ on the expression of c-kit and Gsα. Besides that, higenamine improved the decreased emptying ability of the stomach. In addition, the number of gastric SMCs was strongly decreased and cell morphology became irregular in STZ-induced model group. The treatment of higenamine weakened the harm of STZ on the number and morphology of gastric SMCs. Beyond that, higenamine promoted gastric SMCs proliferation and inhibited gastric SMCs apoptosis in DGP model. Further research revealed that higenamine regulated cell proliferation and apoptosis via activating the β2-AR/PI3K/AKT pathway. Taken together, our research revealed that higenamine maintained the survival of gastric SMCs in DGP rat model via the β2-AR/PI3K/AKT pathway, providing a new sight for the treatment of DGP.
10.1016/j.biopha.2017.08.112
Functional dyspepsia and gastroparesis.
Tack Jan,Carbone Florencia
Current opinion in gastroenterology
PURPOSE OF REVIEW:This review summarizes recent progress in the epidemiology, pathophysiology and treatment of functional dyspepsia and gastroparesis. RECENT FINDINGS:The definition of functional dyspepsia and its subgroups has been revised in the recent Rome IV consensus. In gastroparesis, the symptom pattern and its similarities and differences from functional dyspepsia have been a focus of recent research. In functional dyspepsia, pathophysiological research continued to evaluate gastric sensorimotor dysfunctions, but low-grade inflammatory changes and loss of mucosal integrity in the duodenum is a new topic of intense research. Treatment advances include new prokinetics such as acotiamide and the ghrelin receptor agonist relamorelin. The efficacy of tricyclic antidepressants was recently reviewed and mirtazapine is a new agent used in the treatment of functional dyspepsia and gastroparesis. In gastroparesis, research has focused on the role of macrophages in loss of interstitial cells of Cajal, and on the role of pyloric resistance as a target for therapy, using botulinum toxin injection and gastric per-endoscopic pyloric myotomy. SUMMARY:The functional dyspepsia definition and subgrouping were updated in the Rome IV consensus. Research focuses on duodenal mucosal alterations in functional dyspepsia and pyloric resistance in gastroparesis. New treatments include novel prokinetics and pylorus-directed interventions.
10.1097/MOG.0000000000000393
Exploring the Diabetic Gastroparesis Patient Experience: Patient Exit Interviews.
Ervin Claire M,Reasner David S,Hanlon Jennifer T,Fehnel Sheri E
Advances in therapy
INTRODUCTION:To improve understanding of the diabetic gastroparesis (DGP) patient experience and inform the patient-reported outcome measurement strategy for future trials in DGP, qualitative interviews were conducted with participants in a phase 2 clinical trial of a novel DGP treatment. METHODS:Trial participants were invited to participate in interviews at both the pretreatment visit (PTV) and the end-of-treatment visit (EOTV). The interviews were conducted by experienced qualitative researchers and followed a semistructured interview guide. The PTV interviews focused on patients' DGP symptoms and the impact of DGP on their lives, and the EOTV interviews focused on any symptom changes patients experienced during the trial. RESULTS:Of 90 enrolled trial participants, 78 (86.7%) opted to participate in the interview study. Bloating, stomach fullness, upper abdominal pain, vomiting, constipation, and heartburn or reflux were each reported spontaneously by a majority of the 73 PTV interview participants with evaluable data. These patients commonly reported bloating (n = 20), upper abdominal pain (n = 12), and nausea (n = 11) as their most bothersome DGP symptom. Of 51 EOTV interview participants, 44 (86.3%) reported improvement in at least one DGP symptom either spontaneously or when asked about specific symptoms reported during their PTV interview. CONCLUSION:Bloating, abdominal pain, nausea, constipation, stomach fullness, vomiting, and heartburn were frequently reported by patients as the most bothersome and important-to-treat symptoms. These results support the assessment of these symptoms in future DGP clinical trials, whether for symptom improvement or worsening. FUNDING:Ironwood Pharmaceuticals. TRIAL REGISTRATION:ClinicalTrials.gov identifier NCT02289846.
10.1007/s12325-017-0632-6
Islet Cell Associated Autoantibodies and C-Peptide Levels in Patients with Diabetes and Symptoms of Gastroparesis.
Siraj Elias S,Homko Carol,Wilson Laura A,May Patrick,Rao Ajay D,Calles Jorge,Farrugia Gianrico,Hasler William L,Koch Kenneth L,Nguyen Linda,Snape William J,Abell Thomas L,Sarosiek Irene,McCallum Richard W,Pasricha Pankaj J,Clarke John,Tonascia James,Hamilton Frank,Parkman Henry P
Frontiers in endocrinology
INTRODUCTION:Individuals with diabetes are at increased risk for complications, including gastroparesis. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulting in decreased beta-cell function. Glutamic acid decarboxylase-65 antibody (GADA) is the most commonly used test to assess autoimmunity while C-peptide level is used to assess beta-cell function. Patients with type 2 diabetes mellitus (T2DM), who are GADA positive, are labeled latent autoimmune diabetes in adults (LADA). OBJECTIVE:To characterize patients with T1 and T2DM who have symptoms of gastroparesis using GADA and C-peptide levels and to look for association with the presence of gastroparesis and its symptom severity. DESIGN:113 T1DM and 90 T2DM patients with symptoms suggestive of gastroparesis were studied. Symptom severity was assessed using Gastroparesis Cardinal Symptom Index (GCSI). Serum samples were analyzed for GADA and C-peptide. RESULTS:Delayed gastric emptying was present in 91 (81%) of T1DM and 60 (67%) of T2DM patients ( = 0.04). GADA was present in 13% of T2DM subjects [10% in delayed gastric emptying and 20% in normal gastric emptying ( = 0.2)]. Gastric retention and GCSI scores were mostly similar in GADA positive and negative T2DM patients. GADA was present in 45% of T1DM subjects [46% in delayed gastric emptying and 41% in normal gastric emptying ( = 0.81)]. Low C-peptide levels were seen in 79% T1DM patients and 8% T2DM. All seven T2DM patients with low C-peptide were taking insulin compared to 52% of T2DM with normal C-peptide. CONCLUSION:GADA was present in 13% while low C-peptide was seen in 8% of our T2DM patients with symptoms of gastroparesis. Neither did correlate with degree of delayed gastric emptying or symptom severity. CLINICALTRIALSGOV IDENTIFIER:NCT01696747.
10.3389/fendo.2018.00032
A Critical Review of the Current Clinical Landscape of Gastroparesis.
Fosso Chimi L,Quigley Eamonn M M
Gastroenterology & hepatology
Gastroparesis has emerged as a common gastrointestinal disorder over the past few decades. It has been questioned whether this increase in prevalence reflects a true epidemic or rather the mislabeling of a variety of entities of similar symptomatology accompanied by a delay in the emptying of a meal from the stomach on a radionuclide gastric emptying study. Several factors contribute to this diagnostic morass, including a failure to recognize other conditions with similar symptoms, the relative convenience and accessibility of gastric emptying tests, the pervasive presence of some delay in gastric emptying in a variety of functional gastrointestinal disorders, and the confounding effects of certain therapies (opioids in particular) on gastric emptying rates. As a consequence, the label gastroparesis is affixed to patients whose symptoms have little to do with the rate at which food leaves the stomach and initiates a misdirected course of treatment that includes prokinetics, gastric electrical stimulation, and surgery. This strategy has already led to several well-documented therapeutic failures. When evaluating patients with upper gastrointestinal symptoms, the many facets of gastric and duodenal physiology that could contribute to symptoms should be considered, and a rush to attribute them to delayed gastric emptying should be resisted, as the subset of patients with accurately diagnosed gastroparesis is small. This opinion piece critically reviews the clinical landscape of gastroparesis as well as attempts to outline what should and should not be defined as clinically important gastroparesis.
Exploring Symptom Severity, Illness Perceptions, Coping Styles, and Well-Being in Gastroparesis Patients Using the Common Sense Model.
Woodhouse Sally,Hebbard Geoff,Knowles Simon R
Digestive diseases and sciences
AIMS:This study aimed to examine the relationships between gastroparesis symptom severity, illness perceptions, coping styles, quality of life (QoL), and psychological distress in patients with gastroparesis, guided by the common sense model. METHODS:One hundred and seventy-nine adults with gastroparesis (165 females, 14 males; mean age 41.82 years) completed an online questionnaire. The Gastroparesis Cardinal Symptom Index was used to measure gastroparesis symptom severity, QoL was explored using the PAGI-QOL, illness perceptions were measured using the Brief Illness Perception Questionnaire, the Carver Brief COPE scale assessed coping styles, and psychological distress was investigated using the DASS21. RESULTS:Structural equation modeling resulted in a final model with excellent fit. Gastroparesis symptom severity directly influenced illness perceptions (β = .52, p < .001) and QoL (β = .30, p < .001). Illness perceptions directly influenced maladaptive coping (β = - .64, p < .001), psychological distress (β = - .32, p < .001), and QoL (β = .30, p = .01). Maladaptive coping directly influenced psychological distress (β = .62, p < .001), which in turn had a direct influence on QoL (β = - .38, p < .001). CONCLUSIONS:The final model showed that the influence of gastroparesis symptom severity on psychological distress was fully mediated by illness perceptions, while the influence on QoL was partially mediated by illness perceptions. The study provides guidance for the development of psychological interventions targeted toward improving mediating psychological factors.
10.1007/s10620-018-4975-x
Endoscopic Therapies for Gastroparesis.
Su Andrew,Conklin Jeffrey L,Sedarat Alireza
Current gastroenterology reports
PURPOSE OF REVIEW:Gastroparesis remains a difficult-to-treat disease with limited therapeutic options. Though patients often have a common syndrome of stereotypic symptoms, the underlying pathophysiology is heterogeneous, often leading to variable treatment responses. Due to limitations in medical and surgical therapies, endoscopic options have been increasingly explored. These options can be broadly categorized into pyloric-directed therapy, non-pyloric-directed therapy, and nutritional support. In this review, we will highlight current and emerging endoscopic options, such as gastric per-oral endoscopic myotomy (G-POEM). RECENT FINDINGS:Early retrospective studies on G-POEM offer encouraging results up to one year out, with an acceptable safety profile. Other pyloric-directed therapies, such as pyloric dilation and stenting, have also been explored. While emerging endoscopic therapeutic options are encouraging, efficacy will likely depend on a better characterization of underlying pathophysiology and improved patient selection. Future prospective, controlled studies are needed.
10.1007/s11894-018-0630-0
Glass half empty? Lessons learned about gastroparesis.
McKenzie Patrick,Bielefeldt Klaus
F1000Research
Gastroparesis is defined as a combination of chronic dyspeptic symptoms and delayed emptying of a solid test meal. It remains a difficult-to-treat disorder with a significant impact on quality of life. Although gastroparesis is defined by delayed emptying, several important studies did not find a correlation between this biomarker and symptom severity or treatment success. Thus, some of the more recent trials explored strategies that ranged from antiemetics to antidepressants. Although dietary management showed benefit, most of the other interventions were barely superior to placebo or were not superior at all. Placebo responses were often quite high and this complicates the assessment of active agents. While it complicates the design and interpretation of clinical trials, high response rates for active and sham interventions indicate that we can achieve symptom relief in many patients and thus give them some reassurance. If indeed most therapies are only marginally better than placebo, the differences in adverse effects should be weighed more strongly, a point that is especially important in view of the controversy surrounding metoclopramide. Mechanistic studies introduced the network of macrophages as another potentially important player in the development of gastroparesis. Results are too preliminary and are largely based on preclinical data but show up- and downregulation of cellular elements controlling gastric function. Thus, future developments may teach us how they interfere with some of these mechanisms in clinical settings, potentially making gastroparesis a reversible process.
10.12688/f1000research.14043.1
The Investigation and Treatment of Diabetic Gastroparesis.
Kumar Mohit,Chapman Adam,Javed Saad,Alam Uazman,Malik Rayaz A,Azmi Shazli
Clinical therapeutics
PURPOSE:This review provides an update on the investigations and treatment options for gastroparesis. METHODS:A comprehensive literature search of Medline, PubMed, Embase and OVID was conducted which included all systematic reviews and research articles that focused on the diagnosis, investigations and management diabetic gastroparesis. FINDINGS:Dietary modifications and pharmacologic treatment with prokinetics to increase gastric motility form the mainstay of treatment. However, the use of prokinetics is limited by adverse effects and serious adverse effects, leaving metoclopramide as the only drug approved by the US Food and Drug Administration for the treatment of gastroparesis. Newer therapies, including motilin receptor agonists, ghrelin receptor agonists, and neurokinin receptor antagonists, are currently being investigated. Transpyloric stenting, gastric electrical stimulation, and gastric per-oral endoscopic myotomy provide mechanical options for intervention, and surgical interventions in severe intractable gastroparesis include laparoscopic pyloroplasty or gastrectomy. IMPLICATIONS:Advances to better understand the pathophysiology and management of diabetic gastroparesis have been limited, especially with discordance between symptoms and severity of delay in gastric emptying. Established treatment options are limited; however, recent pharmacologic and surgical interventions show promise.
10.1016/j.clinthera.2018.04.012
Diabetic Gastroparesis: Principles and Current Trends in Management.
Diabetes therapy : research, treatment and education of diabetes and related disorders
This article is a comprehensive review of diabetic gastroparesis, defined as delayed or disordered gastric emptying, including basic principles and current trends in management. This review includes sections on anatomy and physiology, diagnosis and differential diagnosis as well as management and current guidelines for treatment of diabetic gastroparesis. Diabetic gastroparesis (DGp) is a component of autonomic neuropathy resulting from long-standing poorly controlled type 1 and type 2 diabetes. The diagnostic workup of DGp first excludes obstruction and other causes including medications that may mimic delayed/disordered gastric emptying. Targeting nutrition, hydration, symptomatic relief and glycemic control are mainstays of treatment for DGp. Additionally, optimal treatment of DGp includes good glycemic management, often involving customizing insulin delivery using basal-bolus insulin and technology, including sensor-augmented pumps and continuous glucose monitoring systems. Prokinetic medications may be helpful in DGp symptoms, although only limited number of medications is currently available in the USA. Selected medication-refractory patients with DGp may benefit from gastric neuromodulation, and some from surgical interventions including pyloric therapies that can also be done endoscopically. As is true of any of the diabetic complications, prevention of DGp by early and optimal glycemic control is more cost-effective.Funding: Hansa Medcell, India.
10.1007/s13300-018-0454-9
Influence of Gastric Emptying and Gut Transit Testing on Clinical Management Decisions in Suspected Gastroparesis.
Hasler William L,Rao Satish S C,McCallum Richard W,Krause Richard A,Nguyen Linda A,Schulman Michael I,Lee Allen A,Moshiree Baharak,Wo John M,Parkman Henry P,Sarosiek Irene,Wilding Gregory E,Kuo Braden
Clinical and translational gastroenterology
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.
10.14309/ctg.0000000000000084
Mirtazapine for Refractory Gastroparesis.
Marella Hemnishil K,Saleem Nasir,Olden Kevin
ACG case reports journal
Gastroparesis is a chronic condition of delayed gastric emptying in the absence of mechanical outlet obstruction. We report a 47-year-old African American woman with diabetic gastroparesis who presented with intractable nausea, vomiting, and decreased oral intake with electrolyte disturbances. The patient's symptoms were difficult to control with antiemetic and conventional prokinetic agents, and she was started on mirtazapine 15 mg nightly. She experienced an almost complete symptom relief and was able to tolerate solid food within 24-48 hours. We highlight the role of mirtazapine, a 5-HT agonist, as an effective therapy for refractory gastroparesis.
10.14309/crj.0000000000000256
Diabetic Gastroparesis.
Bharucha Adil E,Kudva Yogish C,Prichard David O
Endocrine reviews
This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.
10.1210/er.2018-00161
Influence of Gastric Emptying and Gut Transit Testing on Clinical Management Decisions in Suspected Gastroparesis.
Clinical and translational gastroenterology
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.
10.14309/ctg.0000000000000084
Gastric Electrical Stimulation Is an Effective Treatment Modality for Refractory Gastroparesis in a Postsurgical Patient with Pancreatic Cancer.
Doshi Shreyans,Patel Aniruddh,Stocker Abigail,Scoggins Charles,Agrawal Laila,Abell Thomas
Case reports in gastroenterology
Gastroparesis-related hospital visits contribute significantly to healthcare costs. Gastroparesis can lead to chronic symptoms, such as nausea, vomiting, bloating, early satiety, and abdominal pain. It can result in a significant impairment of quality of life. Diabetes and postsurgery are common causes for gastroparesis, but most cases of gastroparesis are idiopathic in presumed etiology. Malignancy-related gastroparesis has also recently been described in the literature, and pancreatic cancer is a malignancy commonly associated with gastroparesis. Whipple surgery for pancreatic cancer is often complicated by gastroparesis during its postoperative course. We report a case where gastric electrical stimulation was an effective treatment option in the treatment of refractory malignancy-related gastroparesis.
10.1159/000503275
Pharmacological Approaches to Diabetic Gastroparesis: A systematic review of randomised clinical trials.
Asha Mohammad Z,Khalil Sundos F H
Sultan Qaboos University medical journal
Pharmacological interventions of diabetic gastroparesis (DG) constitute an essential element of a patient's management. This article aimed to systematically review the available pharmacological approaches of DG, including their efficacy and safety. A total of 24 randomised clinical trials (RCTs) that investigated the efficacy and/or safety of medications targeting DG symptoms were identified using several online databases. Their results revealed that metoclopramide was the only approved drug for accelerating gastric emptying and improving disease symptoms. However, this medication may have several adverse effects on the cardiovascular and nervous systems, which might be resolved with a new intranasal preparation. Acceptable alternatives are oral domperidone for patients without cardiovascular risk factors or intravenous erythromycin for hospitalised patients. Preliminary data indicated that relamorelin and prucalopride are novel candidates that have proven to be effective and safe. Future RCTs should be conducted based on unified guidelines using universal diagnostic modalities to reveal reliable and comprehensive outcomes.
10.18295/SQUMJ.2019.19.04.004
Proteomics in gastroparesis: unique and overlapping protein signatures in diabetic and idiopathic gastroparesis.
Grover Madhusudan,Dasari Surendra,Bernard Cheryl E,Chikkamenahalli Lakshmikanth L,Yates Katherine P,Pasricha Pankaj J,Sarosiek Irene,McCallum Richard,Koch Kenneth L,Abell Thomas L,Kuo Braden,Shulman Robert J,Gibbons Simon J,McKenzie Travis J,Kellogg Todd A,Kendrick Michael L,Tonascia James,Hamilton Frank A,Parkman Henry P,Farrugia Gianrico
American journal of physiology. Gastrointestinal and liver physiology
Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, "Role of Macrophages, Fibroblasts and Endothelial Cells" was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 × 10; IG FDR = 6.3 × 10]. In DG, properdin expression correlated with GCSI bloating ( = -0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C-ζ type, and complement C2 correlated with 4 h gastric retention ( = -0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophage-driven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis. This study uses SOMAscan, a novel proteomics assay for determination of altered proteins and associated molecular pathways in human gastroparesis. Seventy-three proteins were changed in diabetic gastroparesis, 132 in idiopathic gastroparesis compared with controls. Forty proteins were common in both. Macrophage-based immune dysregulation pathway was most significantly affected in both diabetic and idiopathic gastroparesis. Proteins involved in the complement and prostaglandin synthesis pathway were associated with symptoms and gastric emptying delay in diabetic gastroparesis.
10.1152/ajpgi.00115.2019
Delayed Gastric Emptying Associates With Diabetic Complications in Diabetic Patients With Symptoms of Gastroparesis.
The American journal of gastroenterology
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.
10.14309/ajg.0000000000000410
Gastroparesis: a turning point in understanding and treatment.
Grover Madhusudan,Farrugia Gianrico,Stanghellini Vincenzo
Gut
Gastroparesis is defined by delayed gastric emptying (GE) and symptoms of nausea, vomiting, bloating, postprandial fullness, early satiety and abdominal pain. Most common aetiologies include diabetes, postsurgical and postinfectious, but in many cases it is idiopathic. Clinical presentation and natural history vary by the aetiology. There is significant morbidity and healthcare utilisation associated with gastroparesis. Mechanistic studies from diabetic animal models of delayed GE as well as human full-thickness biopsies have significantly advanced our understanding of this disorder. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system through paracrine and oxidative stress mediators is likely central to the pathogenesis of gastroparesis. Scintigraphy and C breath testing provide the most validated assessment of GE. The stagnant gastroparesis therapeutic landscape is likely to soon see significant changes. Relatively newer treatment strategies include antiemetics (aprepitant), prokinetics (prucalopride, relamorelin) and fundic relaxants (acotiamide, buspirone). Endoscopic pyloromyotomy appears promising over the short term, especially for symptoms of nausea and vomiting. Further controlled trials and identification of the appropriate subgroup with pyloric dysfunction and assessment of long-term outcomes are essential. This review highlights the clinical presentation, diagnosis, mechanisms and treatment advancements for gastroparesis.
10.1136/gutjnl-2019-318712
Efficacy and Safety of Ghrelin Agonists in Patients with Diabetic Gastroparesis: A Systematic Review and Meta-Analysis.
Hong Seung Wook,Chun Jaeyoung,Kim Jihye,Lee Jooyoung,Lee Hyun Jung,Chung Hyunsoo,Cho Soo-Jeong,Im Jong Pil,Kim Sang Gyun,Kim Joo Sung
Gut and liver
Background/Aims:Ghrelin agonists are emerging prokinetic agents for treating gastroparesis. Although recent clinical trials have demonstrated their efficacy in patients with diabetic gastroparesis (DG), the impact of such agents on symptoms and gastric dysmotility remains unclear. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ghrelin agonists in patients with DG. Methods:A search of common electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) was preformed, using keyword combinations that referenced ghrelin and DG and retrieving all eligible randomized controlled trials (RCTs) of ghrelin agonists versus placebo in patients with DG. The primary outcome measure was the change in patient-reported overall gastroparesis symptom scores. Secondary outcomes included the change in gastric emptying time, specific symptoms related to gastroparesis, and adverse events. A random-effects model was applied to all study outcomes. Heterogeneity among studies was determined by the chi-square test and I statistics. Results:We selected six RCTs of patients with DG (n=557) for meta-analysis. Ghrelin agonist administration (vs placebo) significantly improved overall gastroparesis symptoms (standardized mean difference, -0.34; 95% confidence interval, -0.56 to -0.13) and significantly improved symptoms related to gastroparesis, including nausea, vomiting, early satiety, and abdominal pain. Adverse events recorded for ghrelin agonists and placebo did not differ significantly. There was no significant heterogeneity among eligible studies. Conclusions:Compared with placebo, ghrelin agonists are effective and well-tolerated for the treatment of DG.
10.5009/gnl19103
Impact of Cannabinoids on Symptoms of Refractory Gastroparesis: A Single-center Experience.
Barbash Benjamin,Mehta Dhruv,Siddiqui Mohamed Tausif,Chawla Lavneet,Dworkin Brad
Cureus
Background and aims Cannabinoids are increasingly used for medicinal purposes, including neuropathy. Gastroparesis is a neuromuscular disorder and neuropathy plays a large role in its pathogenesis. It is thus reasonable that cannabinoids can serve a beneficial role in the management of gastroparesis. Our study evaluates the effect of cannabinoids on gastroparesis symptoms. Methods Twenty-four (n=24) patients with gastroparesis and refractory symptoms were selected from a single gastroenterology practice associated with a tertiary care medical center. The 'Gastroparesis Cardinal Symptom Index' (GCSI) and an analog scale rating abdominal pain were applied to prospectively assess the effect of cannabinoids, in the form of dronabinol and medical cannabis, on refractory gastroparesis symptoms. Patients completed a GCSI form and rated their abdominal pain, before and after treatment. There was a minimum of 60 days of cannabinoid use between reporting intervals. Total composite GCSI symptom scores, GCSI symptom subset scores, and abdominal pain scores were calculated before and after treatment. Results A significant improvement in the GCSI total symptom composite score was seen with either cannabinoid treatment (mean score difference of 12.8, 95% confidence interval 10.4-15.2; p-value < 0. 001). Patients prescribed marijuana experienced a statistically significant improvement in every GCSI symptom subgroup. Significant improvement in abdominal pain score was also seen with either cannabinoid treatment (mean score difference of 1.6; p-value <0.001). Conclusions Cannabinoids dramatically improve the symptoms of gastroparesis. Furthermore, an improvement in abdominal pain with cannabinoids represents a breakthrough for gastroparesis-associated abdominal pain treatment, for which there are currently no validated therapies.
10.7759/cureus.6430
Caregiver Burden in Gastroparesis and GERD: Correlation with Disease Severity, Healthcare Utilization and Work Productivity.
Digestive diseases and sciences
BACKGROUND:Caregiver burden can be significant in chronic gastrointestinal diseases. No studies have been performed to evaluate caregiver burden in gastroparesis or gastroesophageal reflux disease (GERD). AIMS:(1) Assess the caregiver burden in gastroparesis and GERD patients and healthy volunteers (HVs); (2) correlate the caregiver burden of these patients to the severity of patients' symptoms, healthcare utilization, and work productivity of the patients and the caregivers. METHODS:Patients with gastroparesis and GERD, seen between June 2018 and November 2018, completed Patient Assessment of Gastrointestinal Symptoms, Work Productivity and Activity Impairment (WPAI) and healthcare utilization questionnaires. The caregivers of these patients completed Zarit Burden Interview (ZBI) and WPAI questionnaire. HVs and their potential caregivers also completed these questionnaires. RESULTS:Forty-seven patients (gastroparesis = 31, GERD = 17), 12 HVs, and their caregivers completed questionnaires. Caregivers of gastroparesis patients reported high burden on ZBI (27.7 ± 2.9), greater than the caregivers of GERD (14.9 ± 2.5) and HVs (5.5 ± 1.6, p < 0.01). Among all patients, the caregiver burden had a strong correlation with patients' Gastroparesis Cardinal Symptom Index (GCSI) total score (r = 0.63, p < 0.01) and moderate correlations with the number of patients' physician office visits (r = 0.46, p < 0.01) and the number of work hours missed by caregivers due to patients' symptoms (r = 0.36, p = 0.04). Using multivariable regression, both presence of gastroparesis and other comorbidities significantly predicted caregiver burden, F(2, 33) = 15.94, p < 0.0001, R = 0.491. CONCLUSIONS:Caregivers of gastroparesis patients have high caregiver burden that strongly correlates with patients' GCSI total score. Interventions to reduce symptom severity of Gp patients may reduce the caregiver burden.
10.1007/s10620-019-05723-2
Effectiveness of gastric electrical stimulation in gastroparesis: Results from a large prospectively collected database of national gastroparesis registries.
Neurogastroenterology and motility
BACKGROUND:Gastric electrical stimulation (GES) for treating gastroparesis symptoms is controversial. METHODS:We studied 319 idiopathic or diabetic gastroparesis symptom patients from the Gastroparesis Clinical Research Consortium (GpCRC) observational studies: 238 without GES and 81 with GES. We assessed the effects of GES using change in GCSI total score and nausea/vomiting subscales between baseline and 48 weeks. We used propensity score methods to control for imbalances in patient characteristics between comparison groups. KEY RESULTS:GES patients were clinically worse (40% severe vs. 18% for non-GES; P < .001); worse PAGI-QOL (2.2. vs. 2.6; P = .003); and worse GCSI total scores (3.5 vs. 2.8; P < .001). We observed improvements in 48-week GCSI total scores for GES vs. non-GES: improvement by ≥ 1-point (RR = 1.63; 95% CI = (1.14, 2.33); P = .01) and change from enrollment (difference = -0.5 (-0.8, -0.3); P < .001). When adjusting for patient characteristics, symptom scores were smaller and not statistically significant: improvement by ≥ 1-point (RR = 1.29 (0.88, 1.90); P = .20) and change from the enrollment (difference = -0.3 (-0.6, 0.0); P = .07). Of the individual items, the nausea improved by ≥ 1 point (RR = 1.31 (1.03, 1.67); P = .04). Patients with GCSI score ≥ 3.0 tended to improve more than those with score < 3.0. (Adjusted P = 0.02). CONCLUSIONS AND INFERENCES:This multicenter study of gastroparesis patients found significant improvements in gastroparesis symptoms among GES patients. Accounting for imbalances in patient characteristics, only nausea remained significant. Patients with greater symptoms at baseline improved more after GES. A much larger sample of patients is needed to fully evaluate symptomatic responses and to identify patients likely to respond to GES.
10.1111/nmo.13714
Diabetic Gastroparesis and Glycaemic Control.
Jalleh Ryan,Marathe Chinmay S,Rayner Christopher K,Jones Karen L,Horowitz Michael
Current diabetes reports
PURPOSE OF REVIEW:Gastroparesis is an important complication of diabetes that may have a major impact on the quality of life as a result of upper gastrointestinal symptoms and impaired glycaemic control. Current management strategies include optimising blood glucose control, dietary modifications and supportive nutrition. Pharmacologic approaches with drugs that have prokinetic and/or antiemetic effects are also used widely; however, current available treatments have major limitations. There is increasing recognition that the rate of gastric emptying (GE) is a key determinant of the glycaemic response to a meal. RECENT FINDINGS:There is ongoing uncertainty regarding the impact of longstanding hyperglycaemia on GE, which requires clarification. New diagnostic techniques have been developed to better characterise the mechanisms underlying gastroparesis in individual patients, and these have the potential to lead to more personalised therapy. Management of gastroparesis is complex and suboptimal; novel approaches are desirable. This review summarises recent advances in the understanding of diabetic gastroparesis, with an emphasis on the current therapies that influence GE, and the bidirectional relationship between glycaemic control and GE.
10.1007/s11892-019-1281-8
Gastric electrical stimulation: An emerging therapy for children with intractable gastroparesis.
Setya Aniruddh,Nair Priyanka,Cheng Sam Xianjun
World journal of gastroenterology
Management of gastroparesis remains challenging, particularly in pediatric patients. Supportive care and pharmacological therapies for symptoms remain the mainstay treatment. Although they are effective for mild and some moderately severe cases, often time they do not work for severe gastroparesis. There are a few prokinetics available, yet the use of these drugs is limited by a lack of persistent efficacy and/or safety concerns. Currently, the only modality for adult patients with severe intractable gastroparesis is surgery, ., pyloroplasty and partial gastrectomy, however, this option is generally considered too radical for a growing child. Novel therapeutic approaches, particularly those which are less invasive, are needed. This article explores gastric electrical stimulation (GES), a new therapy for gastroparesis. Unlike others, it neither needs medications nor gastrectomy; rather, it treats through the use of microelectrodes to deliver high-frequency low energy electric stimulation to the pacemaker area of the stomach. Thus, it is tolerated and safe in children. Like in adult patients, GES appears to work in releasing symptoms, improving nutrition, and enhancing the quality of life; it also helps wean off medications and eliminate many needs for hospitalization. Considering the transient nature of gastroparesis in children in many occasions, GES is considered a "bridging" therapy after failed medical interventions and before surgery.
10.3748/wjg.v25.i48.6880
Norovirus-induced Gastroparesis.
Sawin-Johnson Kaylyn N,Packer Clifford D
Cureus
Postviral gastroparesis can result from a variety of viral infections and may cause severe, persistent gastrointestinal symptoms. We report the case of an 85-year-old man with one year of persistent nausea, epigastric pain, early satiety, and 25-pound weight loss after an episode of viral gastroenteritis contracted on a cruise ship. The patient reported that he had tested positive for norovirus shortly after the onset of symptoms. Esophagogastroduodenoscopy revealed no abnormalities, and his symptoms persisted despite treatment for a positive serum H. pylori IgG antibody. Lab workup, including hemoglobin A1c, was otherwise normal, and computed tomography (CT) angiography was unremarkable. A gastric emptying study performed one year after the onset of illness revealed moderate gastroparesis. While most cases of postviral gastroparesis resolve within a year or less, there are a few reports of gastroparetic symptoms lasting two to three years or longer. The pathophysiology might involve a slowly reversible injury to gut neuromodulator cells. Antiviral treatment has not been shown to be effective; symptomatic treatment with antiemetic and prokinetic drugs may be helpful in some cases.
10.7759/cureus.6283
Satiety testing in diabetic gastroparesis: Effects of insulin pump therapy with continuous glucose monitoring on upper gastrointestinal symptoms and gastric myoelectrical activity.
Neurogastroenterology and motility
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.
10.1111/nmo.13720
Central Nervous System Mechanisms of Nausea in Gastroparesis: An fMRI-Based Case-Control Study.
Snodgrass Phillip,Sandoval Hugo,Calhoun Vince D,Ramos-Duran Luis,Song Gengqing,Sun Yan,Alvarado Ben,Bashashati Mohammad,Sarosiek Irene,McCallum Richard W
Digestive diseases and sciences
BACKGROUND/AIMS:Nausea is a major complaint of gastroparesis (GP), and the pathophysiology of this condition is poorly understood. Therefore, this study utilized fMRI to investigate the possible central nervous system (CNS) mechanisms of nausea in 10 GP patients versus 8 healthy controls (HCs). METHODS:Nausea severity was assessed on a 0-10 scale and presented as mean ± SD. Nausea was increased from baseline utilizing up to 30 min of visual stimulation (VS). Functional network connectivity was measured with fMRI at baseline and after 30 min of VS. fMRI data were preprocessed using statistical parametric mapping software. Thirty-four independent components were identified as meaningful resting-state networks (RSNs) by group independent component analysis. The Functional Network Connectivity (FNC) among 5 RSNs considered important in CNS nausea mechanisms was calculated as the Pearson's pairwise correlation. RESULTS:Baseline nausea score in GP patients was 2.7 ± 2.0 and increased to 7.0 ± 1.5 after stimulation (P < 0.01). In HCs nausea scores did not increase from baseline after stimulus (0.3 ± 0.5). When comparing GP patients to HCs after VS, a significant reduction (P < 0.001) in bilateral insula network connectivity compared to the right insula network was detected. No significant differences in connectivity were noted among the other RSNs. Additionally, the average gray matter volume was non-significantly reduced in the insula in GP patients compared to HC. CONCLUSIONS:The insula connectivity network is impaired in nauseated GP patients. This phenomenon could explain the susceptibility of GP patients to nausea or may have resulted from a state of chronic nausea.
10.1007/s10620-019-05766-5
Symptom variability throughout the day in patients with gastroparesis.
Shahsavari Dariush,Yu Daohai,Jehangir Asad,Lu Xiaoning,Zoll Bryan,Parkman Henry P
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:Symptoms of gastroparesis (Gp) can fluctuate at different times of the day. Our aims are (1) To characterize Gp symptom variability throughout the day and in relation to meals and (2) to compare the daily symptom variability in subtypes of Gp-diabetic gastroparesis (DGp) and idiopathic gastroparesis (IGp). METHODS:Patients with Gp filled Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) and completed a modified GCSI-DD seven times a day (GCSI-Throughout the Day [GCSI-TTD]; before and after meals, and before going to bed) over a 2-week period. KEY RESULTS: A total of 44 patients participated (86% females), including 29 (66%) with IGp, 13 (30%) with DGp, and 2 (4%) with postsurgical Gp. Using the GCSI-TTD, patients with Gp reported significant postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. Patients also had progressive worsening of the overall symptom severity, early satiety, stomach fullness, and abdominal pain during the day; however, nausea severity did not differ during the day. Number of vomiting and retching episodes did not show significant variations postprandially or during the day. Patients with IGp had greater symptom severity throughout the day and greater postprandial increase in symptoms compared to patients with DGp. CONCLUSIONS AND INFERENCES: Patients with Gp experience postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. These symptoms also progressively worsen during the day, except for the severity of nausea which persists throughout the day. Understanding the symptom variability in patients with Gp throughout the day and postprandially may be useful in treatment of patients with Gp.
10.1111/nmo.13740
Open-label pilot study: Non-invasive vagal nerve stimulation improves symptoms and gastric emptying in patients with idiopathic gastroparesis.
Neurogastroenterology and motility
BACKGROUND:Gastroparesis, a chronic motility disorder characterized by delayed gastric emptying, abdominal pain, nausea, and vomiting, remains largely unexplained. Medical therapy is limited, reflecting the complex physiology of gastric sensorimotor function. Vagus nerve stimulation is an attractive therapeutic modality for gastroparesis, but prior methods required invasive surgery. In this open-label pilot study, we aimed to assess the benefit of non-invasive vagal nerve stimulation in patients with mild to moderate idiopathic gastroparesis. METHODS:Patients self-administered the gammaCore vagal nerve stimulator for 4 weeks. The gastroparesis cardinal symptom index daily diary (GCSI-dd) was assessed during a two-week run-in period, ≥4 weeks of therapy, and 4 weeks after therapy was completed. Gastric emptying and autonomic function testing were also performed. The primary endpoint was an absolute reduction in CGSI-dd of 0.75 after nVNS. RESULTS:There was a total improvement in symptom scores (2.56 ± 0.76 to 1.87 ± 1.05; P = .01), with 6/15 (40%) participants meeting our primary endpoint. Therapy was associated with a reduction in gastric emptying (T 155 vs 129 minutes; P = .053, CI -0.4 to 45). Therapy did not correct autonomic function abnormalities, but was associated with modulation of reflex parasympathetic activity. CONCLUSIONS:Short-term non-invasive vagal nerve stimulation led to improved cardinal symptoms and accelerated gastric emptying in a subset of patients with idiopathic gastroparesis. Responders had more severe gastric delay at baseline and clinical improvement correlated with duration of therapy, but not with improvements in gastric emptying. Larger randomized sham-controlled trials of greater duration are needed to confirm the results of this pilot study.
10.1111/nmo.13769
Radiofrequency catheter ablation-induced gastroparesis successfully treated with administration of mosapride citrate: two case reports.
Ogasawara Naotaka,Yamaguchi Yoshiharu,Takahama Takuya,Adachi Kazunori,Suzuki Manami,Izawa Shinya,Ebi Masahide,Funaki Yasushi,Sasaki Makoto,Kasugai Kunio
Clinical journal of gastroenterology
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and radiofrequency catheter ablation (RFCA) for pulmonary vein isolation is a well-established therapeutic modality for AF. Transient gastroparesis rarely complicates RFCA. We report two cases of RFCA-induced transient gastroparesis, effectively treated with mosapride citrate administration. Case 1. Computed tomography (CT) performed 4 days after RFCA revealed marked gastric dilatation without any gastric or intestinal obstruction. The patient was fasting and was administered mosapride citrate (5 mg thrice a day). The patient's symptoms improved 6 days later, and CT revealed no gastric dilatation. Esophagogastroduodenoscopy revealed gastric peristalsis without residual food in the stomach. Case 2. CT performed 8 days after RFCA revealed marked gastric dilatation without any gastric or intestinal obstruction. The patient was fasting and was administered pantothenic acid (500 mg/day intravenously for 7 days). However, symptoms persisted, and CT revealed residual food in the stomach. The patient was subsequently administered mosapride citrate (5 mg thrice a day). The patient's symptoms improved 4 days later, and contrast-enhanced gastric X-ray using amidotrizoate meglumine revealed gastric peristalsis, passage of amidotrizoate meglumine into the duodenum, and no gastric dilatation. Mosapride citrate is useful to treat RFCA-induced gastroparesis.
10.1007/s12328-019-01038-x
Gastric peroral endoscopic pyloromyotomy for refractory gastroparesis: a systematic review of early outcomes with pooled analysis.
Spadaccini Marco,Maselli Roberta,Chandrasekar Viveksandeep Thoguluva,Anderloni Andrea,Carrara Silvia,Galtieri Piera Alessia,Di Leo Milena,Fugazza Alessandro,Pellegatta Gaia,Colombo Matteo,Palma Rossella,Hassan Cesare,Sethi Amrita,Khashab Mouen A,Sharma Prateek,Repici Alessandro
Gastrointestinal endoscopy
BACKGROUND AND AIMS:Gastroparesis (GP) is a chronic debilitating condition. Prior pyloric-targeted procedures are either invasive or have questionable efficacy. Gastric peroral pyloromyotomy (G-POEM) has been proposed as a minimally invasive approach. We performed a pooled analysis to evaluate the efficacy and safety of G-POEM for GP. METHODS:Electronic databases (Medline, Scopus, EMBASE) were searched up to January 2019. Studies including patients who underwent G-POEM for GP were eligible. Procedural, clinical, and safety outcomes were assessed by pooling data with a random- or fixed-effect model according to the degree of heterogeneity to obtain a proportion with a 95% confidence interval. RESULTS:Ten studies were eligible for inclusion (292 patients), and 2 of the 10 studies were prospective. Seven studies were performed in the United States, 2 in France, and 1 in China. Endoscopic pyloromyotomy was feasible in all patients. Significant symptomatic improvement was achieved after 83.9% of procedures (mean follow-up, 7.8 ± 5.5 months). When comparing the mean values of pre- and postprocedural scintigraphic evolution, there was a significant decrease of the residual percentage at 2 and 4 hours. The overall adverse events rate was 6.8%. CONCLUSIONS:G-POEM appears to be a promising approach for GP in terms of safety and efficacy outcomes in the short term.
10.1016/j.gie.2019.11.039
Wireless motility capsule compared with scintigraphy in the assessment of diabetic gastroparesis.
Sangnes Dag A,Søfteland Eirik,Bekkelund Mattis,Frey Jakub,Biermann Martin,Gilja Odd Helge,Dimcevski Georg
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:Gastroparesis is a potentially severe late complication of diabetes mellitus. Today, delayed gastric emptying (GE) is mandatory for establishing the diagnosis. In this study, we compared wireless motility capsule (WMC) with gastric emptying scintigraphy (GES). METHODS:Seventy-two patients (49 women) with diabetes mellitus (59 type 1) and symptoms compatible with gastroparesis were prospectively included between 2014 and 2018. Patients were simultaneously examined with GES and WMC. Symptoms were assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) questionnaire. All patients were on intravenous glucose-insulin infusion during testing. KEY RESULTS:WMC and GES correlated r = .74, P < .001. Compared to GES, WMC at ordinary cutoff for delayed GE (300 minutes) had a sensitivity of 0.92, specificity 0.73, accuracy 0.80, and Cohen's kappa κ = 0.61 (P < .001). By receiver operating characteristics (ROC), the area under the curve was 0.95 (P < .001). A cutoff value for delayed GE of 385 minutes produced sensitivity 0.92, specificity 0.83, accuracy 0.86, and Cohen's kappa κ = 0.72 (P < .001). Inter-rater reliability for GE time with WMC was r = .996, κ = 0.97, both P < .001. There was no difference in symptom severity between patients with normal and delayed GE. CONCLUSIONS & INFERENCES:Our findings demonstrate the applicability of WMC as a reliable test to assess gastric emptying in diabetic gastroparesis showing very high inter-observer correlation. By elevating the cutoff value for delayed emptying from 300 to 385 minutes, we found higher specificity without reducing sensitivity.
10.1111/nmo.13771
Botulinum Toxin A Improves Symptoms of Gastroparesis.
Reichenbach Zachary Wilmer,Stanek Steven,Patel Shyam,Ward Sara Jane,Malik Zubair,Parkman Henry P,Schey Ron
Digestive diseases and sciences
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.
10.1007/s10620-019-05885-z
Evaluation of prokinetic agents used in the treatment of gastroparesis.
Roe Neil A,Sakaan Sami,Swanson Heather,Twilla Jennifer D
Journal of drug assessment
Hospitalizations due to gastroparesis have increased in the last 20 years with limited advancements in pharmacologic therapy. Although therapy primarily consists of prokinetic agents, little is known about their effects on hospital outcomes. The aim of our study was to determine whether common prokinetic therapies (metoclopramide and erythromycin) improve outcomes in gastroparesis patients. A retrospective review of adult patients admitted with a primary diagnosis of gastroparesis between 7 January 2011 and 7 January 2014 was conducted. Patients were divided into two groups based on whether they received prokinetic therapy (PRO) during hospitalization or not (NO). Groups were compared to determine length of stay (LOS), 30-day readmission rates, and risk factors affecting these outcomes. Of the 82 patients included in our study, 57 received prokinetic therapy. Mean length of stay (LOS) was 5.8 ± 4.2 days, with a significantly shorter LOS in the NO group (3.7 ± 1.9 vs. 6.7 ± 4.5; = 0.002). Among patients studied, 30.5% were readmitted within 30 days from discharge with no significant reduction in the PRO group (35.1% PRO vs. 20% NO; =0.23). Patients with idiopathic gastroparesis had significantly longer LOS (6.9 ± 4.6 vs. 4.2 ± 2.8; = 0.003). In the PRO group, those who received intravenous (IV) therapy had a significantly shorter LOS (4.9 ± 2.5 IV vs. 8.0 ± 5.3 oral; = 0.01). Treatment of gastroparesis patients with prokinetic agents did not shorten the LOS nor decrease 30-day readmission rates. In those receiving prokinetics, the IV route was associated with reduced LOS.
10.1080/21556660.2016.1278546
Liraglutide-induced Acute Gastroparesis.
Rai Puja,Madi Mahmoud Y,Dickstein Aaron
Cureus
We describe a case of liraglutide-induced acute gastroparesis in a 52-year-old man with a history of well-controlled type 2 diabetes who presented with symptoms of gastric outlet obstruction. The patient responded markedly to conservative treatment with gastric suctioning, antiemetic and prokinetic therapy, and discontinuation of liraglutide with a resolution of his symptoms. This case highlights the importance of considering drug-induced gastroparesis as an etiology of unexplained upper abdominal pain, nausea, and early satiety, especially in the absence of mechanical obstruction.
10.7759/cureus.3791
Glycosylated hemoglobin level may predict the severity of gastroparesis in diabetic patients.
Izzy Manhal,Lee Mindy,Johns-Keating Krysta,Kargoli Faraj,Beckoff Steven,Chun Kwang,Tokayer Aaron
Diabetes research and clinical practice
AIM:To investigate the association between glycemic control represented by glycated hemoglobin (HbA1c) level and the value of 4-h gastric retention on nuclear scan. METHODS:We retrospectively reviewed records of diabetic patients who had 4-h nuclear gastric emptying study, with documented 4-h retention value, between January 1st, 2002 and July 30th, 2014 and had HbA1C level close to the time of the study. We divided our cohort into patients with good glycemic control (HbA1C <7, group A), fair control (7-9, group B), and poor control (>9, group C). The 4-h retention value and symptoms were compared between the 3 groups. RESULTS:Our cohort included 299 patients; mean age was 59 ± 14. The median interval between performing gastric emptying study and measuring HbA1C was 41 days. There were 94 patients in group A (HbA1C 6.1 ± 0.4), 131 patients in group B (HbA1C 7.9 ± 0.5), and 74 patients in group C (HbA1C 10.9 ± 1.6). The mean gastric retention value was different between the three study groups, 8.3% ±17, 11.5% ±19, and 14.4% ±21, respectively (P = .03). CONCLUSION:This is the first study to show that HbA1C level is significantly associated with the 4-h retention value on nuclear gastric emptying scan.
10.1016/j.diabres.2017.10.016
A longitudinal study on patients with diabetes and symptoms of gastroparesis - associations with impaired quality of life and increased depressive and anxiety symptoms.
Teigland Tonje,Iversen Marjolein M,Sangnes Dag A,Dimcevski Georg,Søfteland Eirik
Journal of diabetes and its complications
AIMS:To examine patient reported outcomes (PRO) in patients previously assessed for diabetic gastroparesis, and to investigate how symptoms of gastroparesis evolve over time. In addition, to further evaluate outcomes in those with versus without diabetic gastroparesis at baseline. METHODS:Thirty-four patients with diabetes and gastrointestinal (GI) symptoms, diagnosed with or without diabetic gastroparesis in 2011-2013, were included in this follow-up study. PRO were measured with the Patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM), 36-Item Short Form Survey (SF-36), Patient assessment of upper gastrointestinal disorders-quality of life (PAGI-QOL) and Hospital Anxiety and Depression Scale (HADS). Demographic factors and clinical variables were also recorded. RESULTS:Participants diagnosed with gastroparesis had improved glycemic control (p=0.04) and less GI symptoms (p=0.001), after a follow-up time of 3.2years (mean). Both groups reported severely impaired quality of life (QoL). In total 47% reported symptoms of anxiety, 38% symptoms of depression (scores≥8). GI symptom severity or other PRO could not differentiate between the two groups. CONCLUSIONS:Patients diagnosed with diabetic gastroparesis, as well as those with gastroparesis symptoms - but normal gastric emptying, suffer from severely impaired QoL and a high burden of anxiety and depressive symptoms.
10.1016/j.jdiacomp.2017.10.010
Intragastric Meal Distribution During Gastric Emptying Scintigraphy for Assessment of Fundic Accommodation: Correlation with Symptoms of Gastroparesis.
Orthey Perry,Yu Daohai,Van Natta Mark L,Ramsey Frederick V,Diaz Jesus R,Bennett Paige A,Iagaru Andrei H,Fragomeni Roberto Salas,McCallum Richard W,Sarosiek Irene,Hasler William L,Farrugia Gianrico,Grover Madhusudan,Koch Kenneth L,Nguyen Linda,Snape William J,Abell Thomas L,Pasricha Pankaj J,Tonascia James,Hamilton Frank,Parkman Henry P,Maurer Alan H,
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Impaired fundic accommodation (FA) limits fundic relaxation and the ability to act as a reservoir for food. Assessing intragastric meal distribution (IMD) during gastric emptying scintigraphy (GES) allows for a simple measure of FA. The 3 goals of this study were to evaluate trained readers' (nuclear medicine and radiology physicians) visual assessments of FA from solid-meal GES; develop software to quantify GES IMD; and correlate symptoms of gastroparesis with IMD and gastric emptying. After training to achieve a consensus interpretation of GES FA, 4 readers interpreted FA in 148 GES studies from normal volunteers and patients. Mixture distribution and κ-agreement analyses were used to assess reader consistency and agreement of scoring of FA. Semiautomated software was used to quantify IMD (ratio of gastric counts in the proximal stomach to those in the total stomach) at 0, 1, 2, 3, and 4 h after ingestion of a meal. Receiver-operating-characteristic analysis was performed to optimize the diagnosis of abnormal IMD at 0 min (IMD) with impaired FA. IMD, GES, water load testing, and symptoms were then compared in 177 patients with symptoms of gastroparesis. Reader pairwise weighted κ-values for the visual assessment of FA averaged 0.43 (moderate agreement) for normal FA versus impaired FA. Readers achieved 84.0% consensus and 85.8% reproducibility in assessing impaired FA. IMD based on the division of the stomach into proximal and distal halves averaged 0.809 (SD, 0.083) for normal FA and 0.447 (SD, 0.132) ( < 0.01) for impaired FA. On the basis of receiver-operating-characteristic analysis, the optimal cutoff for IMD discrimination of normal FA from impaired FA was 0.568 (sensitivity, 86.7%; specificity, 91.7%). Of 177 patients with symptoms of gastroparesis, 129 (72.9%) had delayed gastric emptying; 25 (14.1%) had abnormal IMD Low IMD (impaired FA) was associated with increased early satiety ( = 0.02). FA can be assessed visually during routine GES with moderate agreement and high reader consistency. Visual and quantitative assessments of FA during GES can yield additional information on gastric motility to help explain patients' symptoms.
10.2967/jnumed.117.197053
Gastroparesis in Non-Diabetics: Associated Conditions and Possible Risk Factors.
Nassar Yousef,Richter Seth
Gastroenterology research
BACKGROUND:Gastroparesis is a syndrome characterized by delayed gastric emptying in the absence of any mechanical cause. While often associated with diabetes mellitus, most cases of gastroparesis are idiopathic. The purpose of the present paper is to review the co-morbid conditions that most likely associate with non-diabetic gastroparesis. METHODS:The Healthcare Cost and Utilization Project: Nationwide Inpatient Sample (HCUP-NIS) data were used from the year 2013 - 2014 and the Apriori algorithm was run on this subset of patients to identify what co-morbid conditions are most likely associated with gastroparesis. RESULTS:Notable conditions that were found to be most closely linked with gastroparesis were: chronic pancreatitis, end stage renal disease, irritable bowel syndrome, systemic lupus erythematosus, fibromyalgia, and venous thromboembolism. Some of the implications of these findings are briefly discussed. CONCLUSIONS:Gastroparesis is strongly associated with multiple medical conditions which may be potential targets for treatment.
10.14740/gr1060w
Efficacy of Gastric Electrical Stimulation for Gastroparesis: US/European Comparison.
Gastroenterology research
BACKGROUND:Gastric electrical stimulation (GES) is used in both the US and Europe, but little research has investigated the demographics of gastroparesis patients receiving GES by geographic location. METHODS:We compared data from 380 patients, 296 female and 84 males, mean age 42 years, 246 idiopathic (ID), 107 diabetic (DM), and 27 post-surgical (PS). The statistical significance was calculated by Chi-square test and a P-value obtained for ID, DM, and PS. The statistical significance was calculated by Fischer exact test and a P-value obtained comparing male vs. female. RESULTS:European centers had 61 GES patients compared to 319 from the US. In Europe, 100% of patients had gastric emptying test (GET) values available; in the US, it was 75% of patients. European centers had more DM patients (59%) than the US (22%), and a smaller proportion of ID patients (25%) than the US (72%). There was a statistical difference between the causes of gastroparesis in the patients receiving GES (P-value < 0.00001). There was also significant difference in the gender of the patients receiving GES, with a greater proportion of women in the US (P value = 0.0023). CONCLUSIONS:Comparing GES in US vs. Europe demonstrated significant differences in gastroparesis demographics and percentage of patients with GET data. After analyzing the previously discussed results and reviewing recent updates in evidence-based medicine guidelines, the discrepancy and variance in patient populations in the US and Europe emphasizes the need for a database that allows better analysis and treatment of gastroparesis patients worldwide including stimulation therapies.
10.14740/gr1061w
Diabetic Gastroparesis.
Diabetes therapy : research, treatment and education of diabetes and related disorders
This editorial addresses the importance of diabetic gastroparesis as a marker of poor glycemic control, other vascular complications, and suboptimal therapeutic outcomes. Highlighting the need to prevent and manage gastroparesis, it tries to understand why the condition has not received its due share of attention. Complexities in screening, diagnosis, and management all contribute to the lack of focus on this autonomic neuropathy. The editorial reinforces the need to enhance awareness about diabetic gastroparesis and utilize good clinical sense and rational prescription writing in order to limit the impact of this complication.
10.1007/s13300-018-0475-4
Advanced Biventricular Heart Failure due to Left Ventricular Noncompaction Cardiomyopathy Leading to the Formation of a Gastric Bezoar: The Implications of Heart Failure on the Gastrointestinal Tract.
Yunina Daria,Sharma Dikshya,Fazio Richard,Amin Hossam,Tsirlin Yuriy,Shetty Vijay
Case reports in cardiology
Congestive heart failure (CHF) is a chronic disease process affecting multiple organ systems and is associated with significant morbidity and mortality. We report a case of a 43-year-old male with a history of unspecified cardiomyopathy who presented to the hospital with abdominal pain, distention, and nausea for 4 months. He was diagnosed with left ventricular noncompaction and gastroparesis. While symptoms of dyspnea, orthopnea, or increasing peripheral edema are the first that come to mind when thinking of a CHF exacerbation, we must broaden our scope to include such things as nausea, vomiting, abdominal pain, and bloating which can also indicate worsening cardiac function. This case report highlights the significant yet often forgotten gastrointestinal (GI) symptoms that result from advanced biventricular heart failure, with emphasis on impaired gastric and intestinal motility.
10.1155/2018/4386025
Gastroparesis.
Camilleri Michael,Chedid Victor,Ford Alexander C,Haruma Ken,Horowitz Michael,Jones Karen L,Low Phillip A,Park Seon-Young,Parkman Henry P,Stanghellini Vincenzo
Nature reviews. Disease primers
Gastroparesis is a disorder characterized by delayed gastric emptying of solid food in the absence of a mechanical obstruction of the stomach, resulting in the cardinal symptoms of early satiety, postprandial fullness, nausea, vomiting, belching and bloating. Gastroparesis is now recognized as part of a broader spectrum of gastric neuromuscular dysfunction that includes impaired gastric accommodation. The overlap between upper gastrointestinal symptoms makes the distinction between gastroparesis and other disorders, such as functional dyspepsia, challenging. Thus, a confirmed diagnosis of gastroparesis requires measurement of delayed gastric emptying via an appropriate test, such as gastric scintigraphy or breath testing. Gastroparesis can have idiopathic, diabetic, iatrogenic, post-surgical or post-viral aetiologies. The management of gastroparesis involves: correcting fluid, electrolyte and nutritional deficiencies; identifying and treating the cause of delayed gastric emptying (for example, diabetes mellitus); and suppressing or eliminating symptoms with pharmacological agents as first-line therapies. Several novel pharmacologic agents and interventions are currently in the pipeline and show promise to help tailor individualized therapy for patients with gastroparesis.
10.1038/s41572-018-0038-z
Gastric Electrical Stimulation Improves Symptoms of Diabetic Gastroparesis in Patients on Peritoneal Dialysis-2 Case Reports.
Majanović Sanja Klobučar,Zelić Marko,Belančić Andrej,Licul Vanja,Vujičić Božidar,Girotto Neva,Štimac Davor
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Diabetic gastroparesis (DGP), a delay in gastric emptying without obstruction to outflow as a complication of diabetes, typically develops after at least 10 years of diabetes. Cardinal symptoms include nausea, vomiting, early satiety, bloating, and upper abdominal pain. The aim of DGP treatment is to alleviate the severity and frequency of symptoms, improve the level of gastric emptying, ameliorate the patient's nutritional status and to optimize glycemic control. In the treatment of chronic drug-refractory nausea and vomiting secondary to DGP, gastric electrical stimulation (GES) such as Enterra Therapy System (Medtronic Inc., Minneapolis, MN, USA) can be considered. It is well established that diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) requiring renal replacement therapy. The exact prevalence of patients with severe DGP and ESRD is not known; however, finding a therapeutic approach to these patients, particularly those whose gastroparesis symptoms preclude them from undergoing kidney transplant procedure, represents a huge challenge. Our experience suggests that GES implantation can be an effective treatment modality for type 1 diabetic patients on peritoneal dialysis (PD) who are simultaneous pancreas-kidney transplantation candidates, by improving the severity and frequency of gastroparesis symptoms and eventually ensuring their optimal nutritional and fluid intake.
10.3747/pdi.2018.00063
Current and Emerging Therapeutic Options for Gastroparesis.
Myint Aung S,Rieders Brandon,Tashkandi Mohammed,Borum Marie L,Koh Joyce M,Stephen Sindu,Doman David B
Gastroenterology & hepatology
Gastroparesis is a complex, debilitating dysmotility disorder with challenging symptom management. A diagnosis of gastroparesis is based on objectively delayed gastric emptying in the absence of mechanical obstruction. Given the limited efficacy of treatment options and serious side effects, significant research continues for therapeutic options for gastroparesis. Promising investigational pharmacologic therapies include relamorelin, prucalopride, and aprepitant. A novel endoscopic therapy is gastric peroral endoscopic pyloromyotomy, which is associated with improved gastric emptying. This article reviews both current and emerging therapeutic options for gastroparesis, including dietary modification and pharmacologic, electrical stimulation, endoscopic, and surgical therapies. Further research and novel treatment options are needed to address the substantial morbidity of gastroparesis.
Gastroduodenal motility disorders.
Tack Jan,Van den Houte K,Carbone Florencia
Current opinion in gastroenterology
PURPOSE OF REVIEW:This review summarizes recent progress in the epidemiology, pathophysiology and treatment of gastroduodenal motility disorders with an emphasis on functional dyspepsia and gastroparesis. RECENT FINDINGS:Pathophysiological research has focused on the association of delayed emptying and impaired accommodation with symptom pattern. Studies also confirmed the presence of altered mucosal integrity and low-grade immune activation in the duodenum in functional dyspepsia, while changes in numbers of interstitial cells of Cajal and myenteric neurons were confirmed in gastroparesis. Treatment advances in gastroparesis include new prokinetics such as the ghrelin receptor agonist relamorelin and the antiemetic agent aprepitant. The efficacy and use of neuromodulators were reviewed and new management guidelines for functional dyspepsia were published. SUMMARY:Pathophysiological research has focused on cellular changes in gastroparesis and gastroduodenal motility disorders. New treatments include relamorelin and aprepitant for gastroparesis.
10.1097/MOG.0000000000000473
New developments in the treatment of gastroparesis and functional dyspepsia.
Tack Jan,Camilleri Michael
Current opinion in pharmacology
Functional dyspepsia (FD) and gastroparesis are frequent causes of upper gastrointestinal symptoms such as postprandial fullness, early satiation, epigastric pain or burning, upper abdominal bloating, bothersome belching, nausea and vomiting. The underlying pathophysiological mechanisms are heterogeneous and involved mechanisms such as abnormal gastric motility (accommodation, emptying), visceral hypersensitivity, low grade mucosal inflammation and cellular changes in enteric nerves, muscle or interstitial cells of Cajal. Patient-reported outcomes for evaluating treatment efficacy in these conditions were recently developed and validated. Prokinetic agents, which enhance gastric motility, are used for treating both gastroparesis and FD. In FD, besides acid suppressive therapy and Helicobacter pylori eradication, neuromodulators and drugs that enhance gastric accommodation can be applied. In gastroparesis, anti-emetics may also provide symptom relief. Novel approaches under evaluation in these conditions are the fundus relaxing agents acotiamide and buspirone and the antidepressant mirtazapine in FD. For gastroparesis, recently studied agents include the prokinetic ghrelin agonist relamorelin, the prokinetic serotonergic agents velusetrag and prucalopride, the anti-emetic aprepitant and per-endoscopic pyloric myotomy procedures.
10.1016/j.coph.2018.08.015
The content validity of the ANMS GCSI-DD in patients with idiopathic or diabetic gastroparesis.
Journal of patient-reported outcomes
BACKGROUND:The American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary (ANMS GCSI-DD) was developed to meet Food and Drug Administration (FDA) recommendations for patient-reported outcome (PRO) endpoints in gastroparesis studies, including therapeutic trials. The current version of the ANMS GCSI-DD contains five items pertaining to nausea, early satiety, post-prandial fullness, upper abdominal pain, and vomiting. The specific aims of this study were to determine if the appropriate symptoms are included in the ANMS GCSI-DD and to assess the content validity in patients with idiopathic (IG) and diabetic gastroparesis (DG). METHODS:Patients diagnosed with IG or DG were recruited by five clinical sites in the United States for a cross-sectional, qualitative study involving one-on-one in-person concept elicitation and cognitive debriefing interviews. Concept elicitation included open-ended questions to elicit patients' symptoms and impacts of gastroparesis, while cognitive debriefing was designed to assess the comprehensiveness of the ANMS GCSI-DD and clarity of the instructions, items, and response scales. The interviews were audio-recorded and transcribed. Transcripts were analyzed using a content analysis approach with ATLAS.ti. RESULTS:Of 25 patients interviewed, 15 (60%) had IG and 10 (40%) DG. Mean age of the sample was 42.3 years (range: 20-70 years), and most patients were female (n = 19, 76%) and white (n = 19, 76%). During concept elicitation, patients endorsed the following signs and symptoms as relevant and important to their condition: early satiety (n = 25, 100%), post-prandial fullness (n = 25, 100%), nausea (n = 22, 88%), upper abdominal pain (n = 18, 72%), vomiting (n = 15, 60%), and bloating (n = 11, 44%). Many patients (n = 20, 80%) experienced day-to-day symptom change. During cognitive debriefing, patients confirmed the ANMS GCSI-DD content was comprehensive and reflective of their gastroparesis experience. Patients could easily select a response option and describe how they arrived at their answers. Overall, patients found the instrument's instructions, recall period, items, and response options clear and understandable. CONCLUSIONS:The ANMS GCSI-DD was easily understood, found to contain the most important symptoms for patients with IG and DG, and no changes were recommended. Results support the content validity of the ANMS GCSI-DD for clinical trials and clinical care among IG or DG patients.
10.1186/s41687-018-0081-2
Acupuncture for symptomatic gastroparesis.
The Cochrane database of systematic reviews
BACKGROUND:Gastroparesis, a state of delayed gastric emptying in the absence of mechanical obstruction of the stomach, has a substantial impact on people's daily function and quality of life when symptomatic. Current treatment options are based on limited evidence of benefits. Acupuncture is widely used to manage gastrointestinal disorders, although its role in people with symptomatic gastroparesis is unclear. We therefore undertook a systematic review of the evidence. OBJECTIVES:To assess the benefits and harms of acupuncture, in comparison with no treatment, sham acupuncture, conventional medicine, standard care, or other non-pharmacological active interventions for symptom management in people with gastroparesis. SEARCH METHODS:On 26 March 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL Plus, PsycINFO, AMED, Korean medical databases (including Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, KoreaMed, and the National Assembly Library), and Chinese databases (including the China Academic Journal). We also searched two clinical trials registries for ongoing trials. We imposed no language limitations. SELECTION CRITERIA:We selected all randomised controlled trials comparing the penetrating type of acupuncture with no treatment, sham acupuncture, conventional medicine, standard care, and other non-pharmacological active interventions for people with symptomatic gastroparesis of any aetiology (i.e. surgical, diabetic, or idiopathic). Trials reporting outcomes at least four weeks from baseline (short-term outcomes) were eligible. We defined long-term outcomes as those measured after 12 weeks from baseline. The primary outcome was improvement of gastroparesis symptoms in the short term. Secondary outcomes were: improvement of symptoms measured after three months, change in the rate of gastric emptying, quality of life, use of medication, and adverse events in the short and long term. DATA COLLECTION AND ANALYSIS:Two review authors independently selected eligible trials based on predefined selection criteria. Two review authors independently extracted data and evaluated the risk of bias. The review authors contacted investigators to obtain missing information wherever possible. MAIN RESULTS:We included 32 studies that involved a total of 2601 participants. Acupuncture was either manually stimulated (24 studies) or electrically stimulated (8 studies). The aetiology of gastroparesis was diabetes (31 studies) or surgery (1 study). All studies provided data on the proportion of people with symptoms 'improved', although the definition or categorisation of improvement varied among the studies. Most measured only short-term outcomes (28 studies), and only one study employed validated instruments to assess subjective changes in symptoms or reported data on quality of life or the use of medication. Reporting of harm was incomplete; minor adverse events were reported in only seven trials. Most studies had unclear risk of bias in terms of allocation concealment (29/32), outcome assessor blinding (31/32) and selective reporting (31/32), as well as high risk of bias in terms of participant/personnel blinding (31/32). Acupuncture was compared with sham acupuncture (needling on non-acupuncture points), three different types of gastrokinetic drugs (domperidone, mosapride, cisapride), and a histamine H₂ receptor antagonist (cimetidine).There was low-certainty evidence that symptom scores of participants receiving acupuncture did not differ from those of participants receiving sham acupuncture at three months when measured by a validated scale.There was very low-certainty evidence that a greater proportion of participants receiving acupuncture had 'improved' symptoms in the short term compared to participants who received gastrokinetic medication (4 to 12 weeks) (12 studies; 963 participants; risk ratio (RR) 1.25; 95% confidence interval (CI) 1.17 to 1.33, I² = 8%). Short-term improvement in overall symptom scores favouring acupuncture was also reported in five studies with considerable heterogeneity.Acupuncture in combination with other treatments, including gastrokinetics, non-gastrokinetics and routine care, was compared with the same treatment alone. There was very low-certainty evidence in favour of acupuncture for the proportion of participants with 'improved' symptoms in the short term (4 to 12 weeks) (17 studies; 1404 participants; RR 1.22; 95% CI 1.16 to 1.28; I² = 0%). Short-term improvement in overall symptom scores, favouring acupuncture, were also reported (two studies, 132 participants; MD -1.96, 95% CI -2.42 to -1.50; I² = 0%).Seven studies described adverse events, including minor bleeding and hematoma, dizziness, xerostomia, loose stool, diarrhoea, abdominal pain, skin rash and fatigue. The rest of the trials did not report whether adverse events occurred.Subgroup analyses revealed that short-term benefits in terms of the proportion of people with 'improved' symptoms did not differ according to the type of acupuncture stimulation (i.e. manual or electrical). The sensitivity analysis revealed that use of a valid method of random sequence generation, and the use of objective measurements of gastric emptying, did not alter the overall effect estimate in terms of the proportion of people with 'improved' symptoms. The asymmetric funnel plot suggests small study effects and publication bias towards positive reporting. AUTHORS' CONCLUSIONS:There is very low-certainty evidence for a short-term benefit with acupuncture alone or acupuncture combined with gastrokinetic drugs compared with the drug alone, in terms of the proportion of people who experienced improvement in diabetic gastroparesis. There is evidence of publication bias and a positive bias of small study effects. The reported benefits should be interpreted with great caution because of the unclear overall risk of bias, unvalidated measurements of change in subjective symptoms, publication bias and small study reporting bias, and lack of data on long-term outcomes; the effects reported in this review may therefore differ significantly from the true effect. One sham-controlled trial provided low-certainty evidence of no difference between real and sham acupuncture in terms of short-term symptom improvement in diabetic gastroparesis, when measured by a validated scale. No studies reported changes in quality of life or the use of medication.Due to the absence of data, no conclusion can be made regarding effects of acupuncture on gastroparesis of other aetiologies. Reports of harm have remained largely incomplete, precluding assessments of the safety of acupuncture in this population. Future research should focus on reducing the sources of bias in the trial design as well as transparent reporting. Harms of interventions should be explicitly reported.
10.1002/14651858.CD009676.pub2
Prevalence of cardiovascular autonomic neuropathy and gastroparesis symptoms among patients with type 2 diabetes who attend a primary health care center.
AlOlaiwi Lina A,AlHarbi Turki J,Tourkmani Ayla M
PloS one
INTRODUCTION:Cardiovascular autonomic neuropathy (CAN) and gastroparesis are two types of diabetic autonomic neuropathy which could affect patients' quality of life and carry significant morbidity and mortality outcomes. The aim of this study was to estimate the prevalence and risk factors of both CAN and gastroparesis symptoms among patients with type 2 diabetes mellitus (T2DM) at primary health care level. METHODS:A cross-sectional study was conducted among 400 adults with T2DM from April 1, 2017 to March 20, 2018. CAN was defined by the presence of any of the followings: resting tachycardia, orthostatic hypotension or prolonged corrected QT interval in the electrocardiogram. Gastroparesis symptoms were assessed using a validated questionnaire: the Gastroparesis Cardinal Symptom Index. RESULTS:The mean age of study participants and disease duration were 55.26 ± 10.65 years and 10.77 ± 6.89 years, respectively. CAN was present in 15.3% of the participants. Hypertension, smoking, antihypertensive use, body mass index, dyslipidemia and albuminuria were significantly higher in participants with CAN than those without CAN (p<0.05). Prolonged disease duration (p = 0.007) and hypertension (p = 0.004) were independently associated with CAN. Gastroparesis symptoms were present in 6.3% of study participants and were significantly associated with those of female gender (P<0.05). Metformin use emerged as an independent predictor of the presence of at least one symptom (p = 0.001). CONCLUSION:Among Saudi adults with T2DM at primary care level, the prevalence of CAN is significant and is independently related to disease duration and hypertension, indicating the importance of CAN screening, especially for those with prolonged disease duration, and the importance of controlling blood pressure in order to prevent CAN or its consequences. The prevalence of gastroparesis symptoms is 6% and is independently related to metformin use, and therefore, symptomatic screening is required to decide which patients need further evaluation.
10.1371/journal.pone.0209500
Anti-ganglionic AChR antibodies in Japanese patients with motility disorders.
Mukaino Akihiro,Minami Hitomi,Isomoto Hajime,Hamamoto Hitomi,Ihara Eikichi,Maeda Yasuhiro,Higuchi Osamu,Okanishi Tohru,Kokudo Yohei,Deguchi Kazushi,Sasaki Fumisato,Ueki Toshihito,Murata Ken-Ya,Yoshida Takeshi,Kinjo Mistuyo,Ogawa Yoshihiro,Ido Akio,Matsuo Hidenori,Nakao Kazuhiko,Nakane Shunya
Journal of gastroenterology
BACKGROUND:The existence of several autoantibodies suggests an autoimmune basis for gastrointestinal (GI) dysmotility. Whether GI motility disorders are features of autoimmune autonomic ganglionopathy (AAG) or are related to circulating anti-ganglionic acetylcholine receptor (gAChR) antibodies (Abs) is not known. The aim of this study was to determine the associations between autonomic dysfunction, anti-gAChR Abs, and clinical features in patients with GI motility disorders including achalasia and chronic intestinal pseudo-obstruction (CIPO). METHODS:First study: retrospective cohort study and laboratory investigation. Samples from 123 patients with seropositive AAG were obtained between 2012 and 2017. Second study: prospective study. Samples from 28 patients with achalasia and 14 patients with CIPO were obtained between 2014 and 2016, and 2013 and 2017, respectively. In the first study, we analyzed clinical profiles of seropositive AAG patients. In the second study, we compared clinical profiles, autonomic symptoms, and results of antibody screening between seropositive, seronegative achalasia, and CIPO groups. RESULTS:In the first study, we identified 10 patients (8.1%) who presented with achalasia, or gastroparesis, or paralytic ileus. In the second study, we detected anti-gAChR Abs in 21.4% of the achalasia patients, and in 50.0% of the CIPO patients. Although patients with achalasia and CIPO demonstrated widespread autonomic dysfunction, bladder dysfunction was observed in the seropositive patients with CIPO as a prominent clinical characteristic of dysautonomia. CONCLUSIONS:These results demonstrate a significant prevalence of anti-gAChR antibodies in patients with achalasia and CIPO. Anti-gAChR Abs might mediate autonomic dysfunction, contributing to autoimmune mechanisms underlying these GI motility disorders.
10.1007/s00535-018-1477-8
A Positive Correlation Between Gastric and Esophageal Dysmotility Suggests Common Causality.
Zikos Thomas A,Clarke John O,Triadafilopoulos George,Regalia Kirsten A,Sonu Irene S,Fernandez-Becker Nielsen Q,Nandwani Monica C,Nguyen Linda A
Digestive diseases and sciences
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.
10.1007/s10620-018-5175-4
Botulinum Toxin as a Treatment for Refractory Gastroparesis: a Literature Review.
Thomas Ashley,de Souza Ribeiro Bruno,Malespin Miguel,de Melo Silvio W
Current treatment options in gastroenterology
PURPOSE OF REVIEW:Gastroparesis (GP) is a disorder of gastrointestinal motility which leads to delayed gastric emptying in the absence of mechanical obstruction. Treatment is limited as many patients are refractory to dietary modification and the use prokinetic medications carry significant adverse risks. These limitations necessitate more research into experimental therapies. The purpose of this article is to summarize the known information and guidelines on the diagnosis and management of GP and to review the latest literature on experimental treatments. RECENT FINDINGS:Based on the current available literature, there is conflicting data regarding the efficacy of intra-pyloric botulinum injections (IPBIs) for refractory gastroparesis. There have been many open-label trials showing good clinical response, but the only two randomized controlled trials on the matter showed no objective improvement gastric emptying studies. However, both studies were likely underpowered and changes in gastric emptying may not correlate with symptom improvement. As such, these discouraging findings should not be used to exclude botox from the armamentarium of therapies for refractory GP. More large-scale, double-blinded, multicenter randomized control trials are needed to further validate the long-term efficacy and safety of IPBI, as well as gastric peroral endoscopic myotomy (G-POEM), as compared to gastric electrical stimulation (GES) or surgical intervention (i.e., laparoscopic pylorotomy) for refractory gastroparesis.
10.1007/s11938-018-0187-x
Tailored approach to gastroparesis significantly improves symptoms.
Arthur Lauren E,Slattery Lauren,Richardson William
Surgical endoscopy
BACKGROUND:Gastroparesis is difficult to treat and many patients do not report relief of symptoms with medical therapy alone. Several operative approaches have been described. This study shows the results of our selective surgical approach for patients with gastroparesis. MATERIALS AND METHODS:This is a retrospective study of prospective data from our electronic medical record and data symptom sheet. All patients had a pre-operative gastric emptying study showing gastroparesis, an esophagogastroduodenoscopy, and either a CT or an upper GI series with small bowel follow-through. All patients had pre- and post-operative symptom sheets where seven symptoms were scored for severity and frequency on a scale of 0-4. The scores were analyzed by a professional statistician using paired sample t test. RESULTS:58 patients met inclusion criteria. 33 had gastric stimulator (GES), 7 pyloroplasty (PP), 16 with both gastric stimulator and pyloroplasty (GSP), and 2 sleeve gastrectomy. For patients in the GSP group, the second procedure was performed if there was inadequate improvement with the first procedure. There was no mortality. The follow-up period was 6-316 weeks (mean 66.107, SD 69.42). GES significantly improved frequency and severity for all symptoms except frequency of bloating and postprandial fullness. PP significantly improved nausea and vomiting severity, frequency of nausea, and early satiety. Symptom improvement for GSP was measured from after the first to after the second procedure. GSP significantly improved all but vomiting severity and frequency of early satiety, postprandial fullness, and epigastric pain. CONCLUSION:All procedures significantly improved symptoms, although numbers are small in the PP group. GES demonstrates more improvement than PP, and if PP or GES does not adequately improve symptoms GSP is appropriate. In our practice, gastrectomy was reserved as a last resort.
10.1007/s00464-017-5775-7
Reactive oxygen species overproduction and MAP kinase phosphatase-1 degradation are associated with gastroparesis in a streptozotocin-induced male diabetic rat model.
Smiley R,Naik P,McCallum R,Showkat Ali M
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:Diabetic gastroparesis in human and animal models suggest different developmental causes in females vs males. Previously, we demonstrated that although male and female diabetic gastroparetic rats exhibited similarity in disease pathology, molecular mechanisms were different: slow gastric emptying in male diabetic gastroparetic rats was not associated with the level of expression and dimerization of neuronal nitric oxide synthase α in gastric tissues, as was demonstrated in females. Male gastroparesis may involve other mechanisms, such as oxidative stress. We hypothesize that sustained increased reactive oxygen species (ROS) and degradation of MAP kinase phosphatase-1 with subsequent unregulated activation of c-Jun N-terminal kinase and p38MAP kinase pathways are associated with gastroparesis in a male diabetic rat model. METHODS:Using a male rat model of diabetic gastroparesis, we analyzed serum and pyloric tissue for ROS and antioxidant enzyme levels using ELISA; MAP kinase phosphatase-1, c-Jun N-terminal kinases, and p38MAP kinase levels utilized western blotting techniques and phospho-specific antibodies. KEY RESULTS:Both diabetic and diabetic gastroparetic rats demonstrated overproduction of ROS. However, loss of MAP kinase phosphatase-1, a MAP kinase pathway negative regulator, with subsequent activation of c-Jun N-terminal kinase 2 and p38MAP kinase pathways, were observed only in diabetic gastroparetic rats. Diabetic rats without gastroparesis had no significant pathway activation. CONCLUSIONS & INFERENCES:These results suggest that sustained, increased ROS and degradation of MAP kinase phosphatase-1, with subsequent unregulated activation of c-Jun N-terminal kinase and p38MAP kinase pathways, are likely to be factors in diabetic gastroparesis phenotype in a male diabetic rat model.
10.1111/nmo.13218
Intravenous immunoglobulin in drug and device refractory patients with the symptoms of gastroparesis-an open-label study.
Ashat M,Lewis A,Liaquat H,Stocker A,McElmurray L,Vedanarayanan V,Soota K,Howell T,Kedar A,Obert J,Abell T L
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:Gastroparesis is a complex clinical entity; many aspects of which remain unknown. Although most patients have idiopathic, diabetic, or postsurgical gastroparesis, many are thought to have measurable neuromuscular abnormalities. Immunotherapy has recently been utilized to treat suspected autoimmune gastrointestinal dysmotility. METHODS:Fourteen patients with symptoms of gastroparesis (Gp) who were refractory to drug/device were selected from 443 Gp patients from 2013 to 2015 who were treated at the University of Louisville motility center. All patients underwent a structural and psychiatric evaluation along with detailed psychological and behavioral examination to rule out eating disorders. We performed detailed neuromuscular evaluation and all 14 patients received at least 12 weeks of intravenous immunoglobulin (400 mg/kg infusion weekly). Response was defined subjectively (symptomatic improvement) using standardized IDIOM score system. KEY RESULTS:All 14 patients had serological evidence and/or tissue evidence of immunological abnormality. Post-IVIG therapy, there was a significant improvement in symptoms scores for nausea, vomiting, early satiety, and abdominal pain. CONCLUSIONS AND INFERENCES:Although limited by the absence of placebo group, the data illustrate the role of autoimmunity and neuromuscular evaluation in patients with gastroparesis and support the utility of a diagnostic trial of immunotherapy in an effort to improve therapeutic outcomes for such patients.
10.1111/nmo.13256
Idiopathic gastroparesis is associated with specific transcriptional changes in the gastric muscularis externa.
Herring B P,Hoggatt A M,Gupta A,Griffith S,Nakeeb A,Choi J N,Idrees M T,Nowak T,Morris D L,Wo J M
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
BACKGROUND:The molecular changes that occur in the stomach that are associated with idiopathic gastroparesis are poorly described. The aim of this study was to use quantitative analysis of mRNA expression to identify changes in mRNAs encoding proteins required for the normal motility functions of the stomach. METHODS:Full-thickness stomach biopsy samples were collected from non-diabetic control subjects who exhibited no symptoms of gastroparesis and from patients with idiopathic gastroparesis. mRNA was isolated from the muscularis externa and mRNA expression levels were determined by quantitative reverse transcriptase (RT)-PCR. KEY RESULTS:Smooth muscle tissue from idiopathic gastroparesis patients had decreased expression of mRNAs encoding several contractile proteins, such as MYH11 and MYLK1. Conversely, there was no significant change in mRNAs characteristic of interstitial cells of Cajal (ICCs) such as KIT or ANO1. There was also a significant decrease in mRNA-encoding platelet-derived growth factor receptor α (PDGFRα) and its ligand PDGFB and in Heme oxygenase 1 in idiopathic gastroparesis subjects. In contrast, there was a small increase in mRNA characteristic of neurons. Although there was not an overall change in KIT expression in gastroparesis patients, KIT expression showed a significant correlation with gastric emptying whereas changes in MYLK1, ANO1 and PDGFRα showed weak correlations to the fullness/satiety subscore of patient assessment of upper gastrointestinal disorder-symptom severity index scores. CONCLUSIONS AND INFERENCES:Our findings suggest that idiopathic gastroparesis is associated with altered smooth muscle cell contractile protein expression and loss of PDGFRα cells without a significant change in ICCs.
10.1111/nmo.13230
Age-dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system.
Becker Laren,Nguyen Linh,Gill Jaspreet,Kulkarni Subhash,Pasricha Pankaj Jay,Habtezion Aida
Gut
OBJECTIVE:The enteric nervous system (ENS) undergoes neuronal loss and degenerative changes with age. The cause of this neurodegeneration is poorly understood. Muscularis macrophages residing in close proximity to enteric ganglia maintain neuromuscular function via direct crosstalk with enteric neurons and have been implicated in the pathogenesis of GI motility disorders like gastroparesis and postoperative ileus. The aim of this study was to assess whether ageing causes alterations in macrophage phenotype that contributes to age-related degeneration of the ENS. DESIGN:Longitudinal muscle and myenteric plexus from small intestine of young, mid-aged and old mice were dissected and prepared for whole mount immunostaining, flow cytometry, Luminex immunoassays, western blot analysis, enteric neural stem cell (ENSC) isolation or conditioned media. Bone marrow derived macrophages were prepared and polarised to classic (M1) or alternative (M2) activation states. Markers for macrophage phenotype were measured using quantitative RT-PCR. RESULTS:Ageing causes a shift in macrophage polarisation from anti-inflammatory 'M2' to proinflammatory 'M1' that is associated with a rise in cytokines and immune cells in the ENS. This phenotypic shift is associated with a neural response to inflammatory signals, increase in apoptosis and loss of enteric neurons and ENSCs, and delayed intestinal transit. An age-dependent decrease in expression of the transcription factor FoxO3, a known longevity gene, contributes to the loss of anti-inflammatory behaviour in macrophages of old mice, and FoxO3-deficient mice demonstrate signs of premature ageing of the ENS. CONCLUSIONS:A shift by macrophages towards a proinflammatory phenotype with ageing causes inflammation-mediated degeneration of the ENS.
10.1136/gutjnl-2016-312940
Gastroparesis: pharmacotherapy and cardiac risk.
Hellström Per M,Al-Saffar Ahmad
Scandinavian journal of gastroenterology
BACKGROUND:Gastroparesis is characterized by abnormal gastric motility and delayed emptying with symptoms of early satiety, postprandial fullness, bloating, nausea, vomiting and abdominal pain. Pharmacological discovery has been lagging because potential drugs often are associated with abnormalities of electrical conduction of the myocardium due to interaction with cardiac ion channels leading to limited pharmaceutical options for development of new drugs. OBJECTIVE:Addresses the safety of drugs for gastroparesis in terms of cardiotoxicity related to the clinical use of prokinetics and antiemetics. METHODS:Survey of QT drugs List and review of current literature. RESULTS:Many prokinetic drugs are associated with cardiac adverse events and manifest as prolongation of ventricular repolarization, i.e., QT-interval prolongation of the electrocardiogram. This disturbance may develop into a potentially fatal polymorphic ventricular tachyarrhythmia; Torsade de Pointes. Co-administration of prokinetics with other drugs affecting the repolarization process, pharmacokinetic interactions leading to increased blood levels, or the presence of clinical risk factors could further increase the risk for cardiac arrhythmias. CONCLUSIONS:It is important that clinicians managing gastroparesis are aware of the arrhythmogenic potential of drugs used clinically and risk factors that contribute to QT prolongation to safeguard patients at risk for drug-induced cardiac arrhythmia.
10.1080/00365521.2017.1401117
Outcomes of High-Frequency Gastric Electric Stimulation for the Treatment of Severe, Medically Refractory Gastroparesis in Finland.
Laine M,Sirén J,Koskenpato J,Punkkinen J,Rantanen T,Typpö I,Kokkola A,Sallinen V
Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society
BACKGROUND AND AIMS:Severe, medically uncontrollable gastroparesis is a rare entity, which can be treated using a high-frequency gastric electric stimulator implanted surgically. Previous follow-ups have proven positive outcomes with gastric electric stimulator in patients with gastroparesis. The aim of this study was to evaluate the efficacy and safety of gastric electric stimulator in patients, in whom gastroparesis could not be controlled by conservative means in our country. MATERIALS AND METHODS:This is a retrospective multi-center cohort comprising all patients who had been implanted gastric electric stimulator for severe, medically refractory gastroparesis during 2007-2015 in Finland. RESULTS:Fourteen patients underwent implantation of gastric electrical stimulator without any postoperative complications. Laparoscopic approach was used in 13 patients (93%). Prior implantation, all patients needed frequent hospitalization for parenteral feeding, 13 had severe nausea, 11 had severe vomiting, 10 had notable weight loss, and 6 had frequent abdominal pain. After operation, none of the patients required parenteral feeding, 11 patients (79%) gained median of 5.1 kg in weight (P < 0.01), and symptoms were relieved markedly in 8 and partially in 3 patients (79%). Of partial responders, two continued to experience occasional vomiting and one mild nausea. Five patients needed medication for gastroparesis after the operation. One patient did not get any relief of symptoms, but gained 6 kg in weight. No major late complications occurred. CONCLUSION:Gastric electrical stimulator seems to improve the nutritional status and give clear relief of the symptoms of severe, medically uncontrollable gastroparesis. Given the low number of operations, gastric electrical stimulator seems to be underused in Finland.
10.1177/1457496917748222
Gastric Enterovirus Infection: A Possible Causative Etiology of Gastroparesis.
Barkin Jodie A,Czul Frank,Barkin Jamie S,Klimas Nancy G,Rey Irma R,Moshiree Baharak
Digestive diseases and sciences
BACKGROUND:Gastroparesis (GP) is a disabling chronic gastroenterologic disorder with high morbidity that severely impacts patients' quality of life. GP can present acutely after a viral-like gastrointestinal illness resulting in speculation that in some patients, neurologic damage caused by the infection might underlie the pathogenesis of idiopathic gastroparesis (IGP). AIMS:The aim of this study is to document case reports of Enterovirus (EV) infection as a possible cause of IGP. METHODS:Eleven patients referred with a diagnosis of GP underwent workup to exclude known causes of GP. Those with a history of flu-like symptoms or gastroenteritis prior to onset of GP symptoms had gastric biopsies taken during upper endoscopy to assess for the presence of gastric mucosal EV infection. Data on presenting symptoms, extra-intestinal symptoms and conditions, prior nutritional support requirements, upper endoscopy findings, and response to therapy were cataloged. RESULTS:Eleven patients were diagnosed as IGP. Nine had active EV infection on gastric biopsies and were included (7/9 female, mean age 43 years). Eight out of nine received EV treatment with antivirals and/or immune therapies, with a wide degree of variability in treatment regimens. Four out of eight who received EV treatment had symptomatic improvement. One patient had stable symptoms. Three patients are currently undergoing therapy. CONCLUSIONS:Gastric EV infection was frequently detected (82 %) in patients undergoing investigation for IGP. Antiviral and/or immune therapies against EV seem to be favorable, as most of our patients had resolution of their GP symptoms after treatment. This is the first study to identify EV as a possible infectious etiology of IGP.
10.1007/s10620-016-4227-x
Gastrointestinal disorders associated with migraine: A comprehensive review.
Cámara-Lemarroy Carlos R,Rodriguez-Gutierrez Rene,Monreal-Robles Roberto,Marfil-Rivera Alejandro
World journal of gastroenterology
Migraine is a recurrent and commonly disabling primary headache disorder that affects over 17% of women and 5%-8% of men. Migraine susceptibility is multifactorial with genetic, hormonal and environmental factors all playing an important role. The physiopathology of migraine is complex and still not fully understood. Many different neuropeptides, neurotransmitters and brain pathways have been implicated. In connection with the myriad mechanisms and pathways implicated in migraine, a variety of multisystemic comorbidities (e.g., cardiovascular, psychiatric and other neurological conditions) have been found to be closely associated with migraine. Recent reports demonstrate an increased frequency of gastrointestinal (GI) disorders in patients with migraine compared with the general population. Helicobacter pylori infection, irritable bowel syndrome, gastroparesis, hepatobiliary disorders, celiac disease and alterations in the microbiota have been linked to the occurrence of migraine. Several mechanisms involving the gut-brain axis, such as a chronic inflammatory response with inflammatory and vasoactive mediators passing to the circulatory system, intestinal microbiota modulation of the enteric immunological milieu and dysfunction of the autonomic and enteric nervous system, have been postulated to explain these associations. However, the precise mechanisms and pathways related to the gut-brain axis in migraine need to be fully elucidated. In this review, we survey the available literature linking migraine with GI disorders. We discuss the possible physiopathological mechanisms, and clinical implications as well as several future areas of interest for research.
10.3748/wjg.v22.i36.8149
Laparoscopic pyloroplasty versus endoscopic per-oral pyloromyotomy for the treatment of gastroparesis.
Landreneau Joshua P,Strong Andrew T,El-Hayek Kevin,Tu Chao,Villamere James,Ponsky Jeffrey L,Kroh Matthew D,Rodriguez John H
Surgical endoscopy
BACKGROUND:Gastroparesis is a debilitating functional disorder of the stomach characterized by delayed gastric emptying absent an obstructive etiology. Surgical or endoscopic disruption of the pylorus has been utilized to treat this disease, but there is little evidence comparing laparoscopic pyloroplasty (LP) with endoscopic per-oral pyloromyotomy (POP). Herein we describe our experience at our institution using a propensity-matched cohort study to compare outcomes between these procedures. METHODS:All patients who underwent LP for the treatment of gastroparesis from October 2014 through September 2017 at our institution were retrospectively reviewed. Propensity scoring was used to match these patients 1:1 to patients undergoing POP during this time period based on gender, age, and etiology of gastroparesis. Symptom scores using the Gastroparesis Cardinal Symptom Index (GCSI), scintigraphic gastric emptying studies (GES), and perioperative outcomes were compared between matched cohorts. Thirty patients underwent LP for gastroparesis during the study period which were matched 1:1 with patients undergoing POP. The etiology of gastroparesis was 63.3% idiopathic (n = 19), 20.0% post-surgical (n = 6), and 16.7% diabetic (n = 5) in both cohorts. RESULTS:Patients who underwent LP had a longer average length of stay (4.6 vs. 1.4 days, p = 0.003), operative time (99.3 vs. 33.9 min, p < 0.001), and estimated blood loss (12.9 vs. 0.4 mL, p < 0.001). There were more complications in the LP cohort (16.7 vs. 3.3%, p = 0.086), which included surgical site infection (6.7 vs. 0%, p = 0.153), pneumonia (6.7 vs. 0.0%, p = 0.153), and unplanned ICU admission (10.0 vs. 0.0%, p = 0.078). LP and POP both resulted in similar, significant improvements in both in GCSI scores and objective gastric emptying. CONCLUSIONS:Per-oral endoscopic pyloromyotomy (POP) is safe and effective for the treatment of medical refractory gastroparesis. POP has less perioperative morbidity compared to LP with comparative functional outcomes.
10.1007/s00464-018-6342-6
Gastroparesis: Medical and Therapeutic Advances.
Navas Christopher M,Patel Nihal K,Lacy Brian E
Digestive diseases and sciences
Gastroparesis is a chronic, bothersome, and often disabling neuromuscular disorder of the upper gastrointestinal tract. The most frequently reported symptoms of gastroparesis include nausea, vomiting, epigastric pain, early satiety, and unintentional weight loss. Etiologies of gastroparesis include diabetes, connective tissue disorders, prior infection, mesenteric ischemia, and post-surgical complications. The largest category of gastroparesis patients is comprised of those in whom no definitive cause can be identified (idiopathic gastroparesis). The individual and societal burden of gastroparesis is substantial. It considerably reduces patients' quality of life accompanied by a significant negative impact to the healthcare system. The current treatments of gastroparesis are less than ideal. Dietary modification may improve symptoms in patients with mild disease. Metoclopramide is the only medication currently approved for the treatment of gastroparesis; however, it is associated with adverse effects in a sizable proportion of patients. Other medications are frequently employed to treat symptoms of nausea and vomiting, although technically all are used off-label since they are not FDA approved for the treatment of gastroparesis. These data highlight the need to identify novel, more effective treatment options for this disabling disease. This review will provide a brief synopsis on the epidemiology, etiology, and impact of gastroparesis, discussing new therapeutic advances.
10.1007/s10620-017-4679-7
Analysis of the Relationship between Infection and Diabetic Gastroparesis.
Huang Ju
Chinese medical journal
BACKGROUND:Whether Helicobacter pylori infection is associated with diabetic gastroparesis (DGP) is unclear. This study aimed to investigate the potential correlation between H. pylori infection and DGP. METHODS:In this study, 163 patients with type 2 diabetes mellitus and 175 nondiabetic patients who were treated in our department were divided into DGP, simple diabetes, non-DGP (NDG), and normal groups based on their conditions. The H. pylori infection rate in each group was calculated. H. pylori eradication therapy was performed for patients with H. pylori infection in each group. The eradication rates were compared between the groups, and the improvements in gastroparesis-associated symptoms were compared before and after treatment in patients with DGP. RESULTS:The H. pylori infection rate was 74.6% in the DGP group, which was significantly higher than that in the simple diabetes (51.1%, P < 0.01), NDG (57.7%, P < 0.05), and normal groups (48.0%, P < 0.01). With increased disease course, the incidence of DGP and the H. pylori infection rate gradually increased (P < 0.05). In the DGP group, the incidences of upper abdominal pain and distention, early satiety, and anorexia were 75.5%, 66.0%, and 67.9%, respectively, before eradication treatment; and 43.4%, 35.8%, and 39.6%, respectively, after eradication treatment, and the difference was statistically significant (P < 0.01). In patients with DGP with successful H. pylori eradication, the number of barium strips discharged after eradication was 5.9 ± 1.0, which was significantly larger than that before treatment (4.1 ± 0.7, P < 0.01). In addition, the number of barium strips discharged was significantly larger in patients with DGP with successful H. pylori eradication than those with failed H. pylori eradication (P < 0.01). CONCLUSIONS:DGP development might be associated with H. pylori infection. H. pylori eradication can effectively improve dyspepsia-associated symptoms and delayed gastric emptying in patients with DGP.
10.4103/0366-6999.218012
The quantification and assessment of depression and anxiety in patients with postoperative gastroparesis syndrome.
Zheng Li-Juan,Ma Jia-Chi,Fang Dong,Wu Li-Gang,Gong Zhen-Qiang,Qi Jian-Bo,Zhao Xiao-Dan,Du Jian-Bo,Ma Pei-Lan
Therapeutics and clinical risk management
BACKGROUND:This study aimed to analyze the stage-situation depression and anxiety as well as independent influential factors in patients with postsurgical gastroparesis syndrome (PGS) and to provide dependent indications for treatment. PATIENTS AND METHODS:The self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to test the depression and anxiety of 53 patients with PGS, who were treated in the Department of Gastroenterological Surgery of Gansu Provincial Hospital from January 2012 to October 2016. A comparison between the SDS or SAS scores of patients with PGS and without PGS was undertaken; then, we retrospectively analyzed the factors influencing depression and anxiety in PGS patients. RESULTS:The patients with PGS' mean scores of depression and anxiety were 49.92±11.37 and 50.91±6.57, respectively, which were higher than that of patients without PGS in the Chinese population (<0.05). The results of multivariate logistic regression analysis indicated that the independent influential factors of depression and anxiety in patients with PGS included course of disease, pancreatic juice leakage, preoperative outflow tract obstruction, postoperative abdominal infection, and anastomotic complication (<0.05). Patients with a disease course longer than 30 days; with pancreatic juice leakage; and who suffered from preoperative outflow tract obstruction, postoperative abdominal infection, and anastomotic complication had higher ratios of depression and anxiety. CONCLUSION:Depression and anxiety are clearly evident in patients with PGS, and we should pay attention to this phenomenon and provide appropriate treatment.
10.2147/TCRM.S155358
Muscularis macrophages: Key players in intestinal homeostasis and disease.
De Schepper Sebastiaan,Stakenborg Nathalie,Matteoli Gianluca,Verheijden Simon,Boeckxstaens Guy E
Cellular immunology
Macrophages residing in the muscularis externa of the gastrointestinal tract are highly specialized cells that are essential for tissue homeostasis during steady-state conditions as well as during disease. They are characterized by their unique protective functional phenotype that is undoubtedly a consequence of the reciprocal interaction with their environment, including the enteric nervous system. This muscularis macrophage-neuron interaction dictates intestinal motility and promotes tissue-protection during injury and infection, but can also contribute to tissue damage in gastrointestinal disorders such as post-operative ileus and gastroparesis. Although the importance of muscularis macrophages is clearly recognized, different aspects of these cells remain largely unexplored such their origin, longevity and instructive signals that determine their function and phenotype. In this review, we will discuss the phenotype, functions and origin of muscularis macrophages during steady-state and disease conditions. We will highlight the bidirectional crosstalk with neurons and potential therapeutic strategies that target and manipulate muscularis macrophages to restore their protective signature as a treatment for disease.
10.1016/j.cellimm.2017.12.009
Clinical Efficacy and Microbiome Changes Following Fecal Microbiota Transplantation in Children With Recurrent Clostridium Difficile Infection.
Li Xiaolu,Gao Xuefeng,Hu Hui,Xiao Yongmei,Li Dan,Yu Guangjun,Yu Dongbao,Zhang Ting,Wang Yizhong
Frontiers in microbiology
Fecal microbiota transplantation (FMT) has been shown as an effective treatment for recurrent clostridium difficile infection (RCDI) in adults. In this study, we aim to evaluate the clinical efficacy of FMT in treating children with RCDI, and explore fecal microbiota changes during FMT treatment. A total of 11 RCDI subjects with a median age of 3.5 years were enrolled in this single-center prospective pilot study. All patients were cured (11/11, 100%) by FMT either through upper gastrointestinal tract route with a nasointestinal tube (13/16, 81.2%) or lower gastrointestinal tract route with a rectal tube (3/16, 18.8%). The cure rate of single FMT was 63.6% (7/11), and 4 (4/11, 36.4%) cases were performed with 2 or 3 times of FMT. Mild adverse events were reported in 4 children (4/11, 36.4%), including transient diarrhea, mild abdominal pain, transient fever and vomit. Gut microbiota composition analysis of 59 fecal samples collected from 34 participants (9 RCDI children, 9 donors and 16 health controls) showed that the diversity was lower in pediatric RCDI patients before FMT than the healthy controls and donors, and fecal microbial community of pre-FMT samples ( diversity) was apart from that of healthy controls and donors. No significant differences in diversity, diversity or phylogenetic distance were detected between donors and healthy controls. Both the richness and diversity of gut microbiota were improved in the pediatric RCDI patients after FMT, and the bacteria community was shifted closer to the donor and healthy control group. Furthermore, FMT re-directed gut microbiome functions of pediatric RCDI toward a health state. Our results indicate that it is safe and tolerant to use FMT in treating pediatric RCDI. FMT shifted the gut microbiome composition and function in children with RCDI toward a healthy state.
10.3389/fmicb.2018.02622
Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia.
Hanada Shigeo,Pirzadeh Mina,Carver Kyle Y,Deng Jane C
Frontiers in immunology
Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function ("dysbiosis") in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.
10.3389/fimmu.2018.02640