Difference in Cyclic Versus Non-cyclic Symptom Patterns in Patients with the Symptoms of Gastroparesis Undergoing Bioelectric Therapy.

INTRODUCTION: Patients with gastroparesis (Gp) have symptoms with or without a cyclic pattern. This retrospective study evaluates differences in cyclic vs. non-cyclic symptoms of Gp by analyzing mucosal electrogastrogram (mEG), familial dysautonomias, and response to gastric stimulation. METHODS: 37 patients with drug refractory Gp, 7 male and 30 female, with a mean age of 41.4 years, were studied. 18 had diabetes mellitus, 25 had cyclic (Cyc), and 12 had a non-cyclic (NoCyc) pattern of symptoms. Patients underwent temporary mucosal gastric stimulator (tGES) placement, which was done as a trial before permanent stimulator (GES) placement. Electrogastrogram (EGG) by mucosal (mEG) measures, including frequency, amplitude, and frequency-amplitude ratio (FAR), were pre- and post-tGES. Patients' history of personal and familial dysautonomias, quality of life, and symptom scores were recorded. Baseline vs. follow-ups were compared by paired t tests and McNemar's tests. T tests contrasted symptom scores, gastric emptying tests (GET), and mEG measures, while chi-squared tests deciphered comorbidity differences between two groups and univariate and multivariate analyses. RESULTS: There were significantly more patients with diabetes in the Cyc group vs. the NoCyc group. Using a 1 point in symptom outcome, 18 patients did not improve and 19 did improve with tGES. Using univariable analysis, with the cyclic pattern as a predictor, patients exhibiting a cyclic pattern had an odds ratio of 0.22 (95% CI 0.05-0.81, p = 0.054) for achieving an improvement of at least one unit in vomiting at follow-up from baseline. The mucosal electrogastrogram frequency to amplitude ratio (FAR) for the "not Improved" group was 19.6 [3.5, 33.6], whereas, for the "Improved" group, it was 54.3 [25.6, 72.5] with a p-value of 0.049. For multivariate logistic regression, accounting for sex and age squared, patients exhibiting a cyclic pattern had an adjusted odds ratio (OR) of 0.16 (95% CI 0.03-0.81, p = 0.027) for achieving an improvement of at least one unit in vomiting at follow-up from baseline. The two groups had no significant differences in the personal or inherited history of investigated familial patterns. CONCLUSION: This study shows differences in Gp patients with Cyc vs. NoCyc symptoms in several areas. Larger studies are needed to elicit further differences between the two groups about cycles of symptoms, EGG, findings, familial patterns, and response to mucosal GES.

Pathogenesis and management of diabetic gastroparesis: An updated clinically oriented review.

BACKGROUND AND AIMS: Diabetic gastroparesis (DGp) is a common and preventable complication of uncontrolled diabetes mellitus (D.M.) and significantly affects the Quality of Life of patients. Diagnosis and management present as a clinical challenge due to the disease's complexity and limited effective therapeutic options. This review aims to comprehensively outline the pathogenesis, diagnosis, and management of diabetic gastroparesis, evaluating evolving approaches to guide clinicians and provide future recommendations. METHODS: A literature review was conducted on scholarly databases of PubMed, Google Scholar, Scopus and Web of Science encompassing published articles, gray literature and relevant clinical guidelines. Data were synthesized and analyzed to provide a comprehensive overview of diabetic gastroparesis, focusing on pathogenesis, diagnosis, and management. RESULTS: The review intricately explores the pathogenesis contributing to diabetic gastroparesis, emphasizing autonomic neuropathy, oxidative stress, inflammation, hormonal dysregulation, microbiota alterations, and gastrointestinal neuropathy. Primary management strategies are underscored, including lifestyle modifications, symptom relief, and glycemic control. The discussion encompasses pharmacological and surgical options, highlighting the importance of a multidisciplinary approach involving various healthcare professionals for comprehensive patient care. CONCLUSION: This review offers a thorough understanding of pathogenesis, diagnosis, and management of diabetic gastroparesis, underlining evolving approaches for clinicians. A multidisciplinary approach is crucial to address both the physical and mental health aspects of diabetes and its complications.

Diabetic gastroparesis: a disease for which long-term therapeutic benefits are difficult to obtain.

The pathophysiology of diabetic gastroparesis (DGP), a common complication in diabetic patients, is not fully known. Its development has been linked to several causes, including hyperglycaemia, vagal nerve dysfunction, aberrant Cajal's interstitial cell network (ICC), lack of nerve nitric oxide synthase (nNOS) expression in the intermuscular plexus, and hormonal alterations in the gastrointestinal tract. Glucose management, diet control, gastric stimulants, anti-emetic medications, Helicobacter pylori eradication, stomach electrical stimulation, and surgery are the main current treatments. These methods, however, could have unfavourable consequences. By examining recent studies and literature reviews, we outline the state of the study on diabetic gastroparesis in this paper.

A gluco-mindful approach to diabetic gastroparesis.

Diabetes gastroparesis is a common manifestation of autonomic neuropathy in persons with long-standing, uncontrolled diabetes. Most discussion about its management revolves around the mitigation of symptoms. Here, we share tips on choosing the right glucose-lowering medication, based upon predominant symptomatology of gastroparesis. We highlight about insulin preparations, and their timing of administration, can be tailored according to need. We also emphasize the need to choose oral glucose lowering drugs with care.

Nutritional Assessment in Patients after Gastric Electrical Stimulation (GES).

BACKGROUND: Gastric electrical stimulation (GES) is used for patients with drug-refractory gastroparesis (Gp) symptoms. Approximately two-thirds of patients with Gp symptoms are either overweight or obese. We aimed to assess symptoms and nutritional status pre-GES and post-GES placement in a large sample of drug-refractory Gp patients. METHODS: We conducted a chart review of 282 patients with drug-refractory Gp who received temporary followed by permanent GES at an academic medical center. Gastrointestinal symptoms were collected by a traditional standardized PRO (0-4, 0 being asymptomatic and 4 being worst symptoms), baseline nutritional status by BMI plus subjective global assessment (SGA score A, B, C, for mild, moderate, and severe nutritional deficits), ability to tolerate diet, enteral tube access, and parenteral therapy were assessed at baseline and after permanent GES placement. RESULTS: Comparing baseline with permanent, GES was found to significantly improve upper GI symptoms in all quartiles. Of the 282 patients with baseline body mass index (BMI) information, 112 (40%) patients were severely malnourished at baseline, of which 36 (32%) patients' nutritional status improved after GES. Among all patients, 76 (68%) patients' nutritional status remained unchanged. Many patients with high BMI were malnourished by SGA. CONCLUSION: We conclude that symptomatic patients of different BMIs showed improvement in their GI symptoms irrespective of baseline nutritional status. Severely malnourished patients were found to have an improvement in their nutritional status after GES therapy. We conclude that BMI, even if high, is not by itself a contraindication for GES therapy for symptomatic patients.

Noninvasive electrical neuromodulation for gastrointestinal motility disorders.

INTRODUCTION: Gastrointestinal motility disorders are highly prevalent without satisfactory treatment. noninvasive electrical neuromodulation is an emerging therapy for treating various gastrointestinal motility disorders. AREAS COVERED: In this review, several emerging noninvasive neuromodulation methods are introduced, including transcutaneous auricular vagal nerve stimulation, percutaneous auricular vagal nerve stimulation, transcutaneous cervical vagal nerve stimulation, transcutaneous electrical acustimulation, transabdominal interference stimulation, tibial nerve stimulation, and translumbosacral neuromodulation therapy. Their clinical applications in the most common gastrointestinal motility are discussed, including gastroesophageal reflux disease, functional dyspepsia, gastroparesis, functional constipation, irritable bowel syndrome, and fecal incontinence. PubMed database was searched from 1995 to June 2023 for relevant articles in English. EXPERT OPINION: Noninvasive neuromodulation is effective and safe in improving both gastrointestinal symptoms and dysmotility; it can be used when pharmacotherapy is ineffective. Future directions include refining the methodology, improving device development and understanding mechanisms of action.

A global bibliometric and visualized analysis of the status and trends of gastroparesis research.

BACKGROUND: Gastroparesis has a substantial impact on the quality of life but has limited treatment options, which makes it a public health concern. No bibliometric studies on gastroparesis have been published thus far. Thus, this article aims to summarize and analyze research hotspots to provide a reference for clinical researchers. MATERIALS AND METHODS: Gastroparesis-related research articles were searched in the Web of Science Core Collection (WOSCC), and relevant information was extracted after screening. A total of 1033 documents were analyzed with the bibliometric method using Microsoft Excel, Citespace, and VOSviewer. RESULTS: Overall, our search retrieved 1033 papers contributed by 966 research institutions from 53 countries. Since 1980, publications in this field have increased rapidly. United States (n = 645) and Temple University (n = 122) were the most productive country and institution, respectively. Parkman, with 96 publications, was the most prominent author. CONCLUSIONS: Research hotspots in gastroparesis can be summarized into four domains: innovation in diagnostic modalities, change of oral therapeutic agents, choice of surgical interventions, and pathological mechanisms. Future research on gastroparesis should focus on the quality of life of patients, diagnostic techniques, pyloromyotomy, and transpyloric stent placement.

Underutilisation of gastric emptying studies and underrecognition of gastroparesis in people with diabetes treated in a hospital setting.

Delayed gastric emptying occurs in up to 30% of patients with long-standing diabetes and causes significant morbidity. We performed a retrospective cohort study of 341 patients who had participated in a gastric emptying study from 2018 to 2021 in a large teaching hospital. Given the expected prevalence of gastroparesis in people with diabetes, there were fewer studies than anticipated, which could lead to gastroparesis underrecognition.

Gastric Electrical Stimulation as a New Treatment Modality for Refractory Nausea and Vomiting with Normal Gastric Emptying.

Nausea and vomiting are cardinal symptoms affecting many patients with delayed or normal gastric emptying. The current therapies are very limited and less than optimal. Therefore, gastrointestinal symptoms persist despite using all the standard approaches for gastroparesis, functional dyspepsia, or unexplained nausea and vomiting. It is well established that gastric electrical stimulation (GES) is effective in reducing nausea and vomiting in gastroparesis, but there are essentially no data available that detail the efficacy of GES in symptomatic patients without gastroparesis. We present a unique case of a female patient diagnosed with functional dyspepsia, whose nausea and vomiting which were refractory to all standard therapies were successfully addressed with the implantation of a GES system.

Gastroparesis: time for a paradigm change.

PURPOSE OF REVIEW: Gastroparesis (GP) is a syndrome defined by symptoms and delayed gastric emptying in the absence of mechanical obstruction. Typical symptoms include nausea, vomiting, abdominal pain, and early satiety. Only one medication is currently FDA-approved for the treatment of GP. This review highlights recent research findings pertaining to GP and provides evidence to support a change in the current GP diagnostic and treatment paradigm. RECENT FINDINGS: An analysis of GP trials over the past four decades demonstrates the power of placebo and the need to perform longer studies with clearly defined patient populations. Two studies highlight the need to evaluate patients with suspected GP carefully and to perform gastric emptying studies properly. The misdiagnosis of GP symptoms is reviewed, preceded by a discussion of whether GP should be considered a disorder of gut-brain interaction. Finally, new data on therapies that target the pylorus are highlighted. SUMMARY: Gastroparesis is frequently over-diagnosed and incorrectly diagnosed. Performing a proper gastric emptying study which adheres to standard protocol, and accurately interpreting the results in the context of the individual patient, are critical to making an accurate diagnosis of GP. The treatment paradigm needs to shift from simply aiming to accelerate gastric emptying to treating global symptoms of a chronic syndrome that may represent gut-brain dysfunction in many patients.

Gastric Alimetry in the Management of Chronic Gastroduodenal Disorders: Impact to Diagnosis and Health Care Utilization.

INTRODUCTION: Chronic gastroduodenal symptoms are frequently overlapping within existing diagnostic paradigms, and current diagnostic tests are insensitive to underlying pathophysiologies. Gastric Alimetry has emerged as a new diagnostic test of gastric neuromuscular function with time-of-test symptom profiling. This study aimed to assess the impact to diagnosis and health care utilization after the introduction of Gastric Alimetry into clinical care. METHODS: Consecutive data of patients from 2 tertiary centers with chronic gastroduodenal symptoms (Rome-IV defined or motility disorder) having integrated care and Gastric Alimetry testing were evaluated. Changes in diagnoses, interventions, and management were quantified. Pretest and posttest health care utilization was reported. A preliminary management framework was established through experiential learning. RESULTS: Fifty participants (45 women; median age 30 years; 18 with gastroparesis, 24 with chronic nausea and vomiting syndrome, and 6 with functional dyspepsia) underwent Gastric Alimetry testing. One-third of patients had a spectral abnormality (18% dysrhythmic/low amplitude). Of the remaining patients, 9 had symptoms correlating to gastric amplitude, while 19 had symptoms unrelated to gastric activity. Gastric Alimetry aided management decisions in 84%, including changes in invasive nutritional support in 9/50 cases (18%; predominantly de-escalation). Health care utilization was significantly lower post-Gastric Alimetry testing when compared with the average utilization cost in the year before Gastric Alimetry testing (mean ± SD $39,724 ± 63,566 vs $19,937 ± 35,895, P = 0.037). DISCUSSION: Gastric Alimetry aided diagnosis and management of patients with chronic gastroduodenal symptoms by enabling phenotype-informed care. The high majority of results aided management decisions, which was associated with reduced health care utilization.

Low-intensity pulsed ultrasound at ST36 improves the gastric motility by TNF-α/IKKß/NF-κB signaling pathway in diabetic rats.

BACKGROUND AND AIM: Low-intensity pulsed ultrasound (LIPUS) can effectively regulate the central and peripheral nervous system. However, whether LIPUS could act on acupuncture points to modulate the activity of peripheral nervous has rarely been studied. Our study aimed to investigate whether LIPUS at ST36 could improve gastric emptying in diabetic gastroparesis rats. METHODS: Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DM), and diabetic gastroparesis LIPUS treated group (LIPUS). The body weight and blood glucose were recorded every week. Glucose tolerance, gastric emptying rate, and gastric motility were measured before and after treatment. Gastric motility was assessed by ultrasonic examination and Muscle strip experiment. The expression level of c-Kit was assessed by immunohistochemistry staining. Levels of TNF-α, p-NF-κB p-65, NF-κB p-65, and p-IKKß, IKKß were measured by western blot. RESULTS: We reported LIPUS at an intensity of 0.88 W/cm2 exhibited significant differences in functional recovery of gastric delayed emptying in diabetic rats. Through ultrasound gastric motility functional testing and analysis of gastric antral smooth muscle strips indirectly and directly proved the effectiveness of LIPUS for the recovery of gastric delayed emptying. Pathological analysis and western blot indicated that the mechanism by which LIPUS applied to ST36 improved gastric motility may be partially attributed to the inhibition of the TNF-α/IKKß/NF-κB signaling pathway, thereby rescuing the damaged interstitial cells of Cajal network. CONCLUSION: LIPUS at ST36 improved the gastric motility and rescued the damaged networks of interstitial cells of Cajal. LIPUS may have a promising therapeutic potential for diabetic gastroparesis.

Gastroparesis and Gastroparesis Syndromes as Neuromuscular Disorders.

Gastroparesis syndromes (GpS) are a spectrum of disorders presenting with characteristic symptoms increasingly recognized as being gastrointestinal (GI) neuromuscular disorders (NMDs). This review focuses on GpS as a manifestation of neurologic disorders of GI NMD. GpS can be associated with systemic abnormalities, including inflammatory, metabolic, and serologic disorders, as well as autoimmune antibodies via nerve and muscle targets in the GI tract, which can be treated with immunotherapy, such as intravenous immunoglobulin. GpS are associated with autonomic (ANS) and enteric (ENS) dysfunction. Disorders of ANS may interact with the ENS and are the subject of continued investigation. ENS disorders have been recognized for a century but have only recently begun to be fully quantified. Anatomic structural changes in the GI tract are increasingly recognized in GpS. Detailed descriptions of anatomic changes in GpS, and their correlation with physiologic findings, have opened a new era of investigation. The management of GpS, when viewed as GI NMD, has shifted the paradigms of both diagnosis and treatment. This article concludes with current approaches to GpS directed at underlying neuromuscular pathology.

Treatment of postsurgical gastroparesis syndrome with Fu's subcutaneous needling: A case report.

Postsurgical gastroparesis syndrome is a syndrome of significantly delayed gastric emptying in the absence of mechanical obstruction after surgery. We presented a case of 69-year-old male patient who suffered from progressive nausea, vomiting and stomach fullness, with a bloating abdomen ten days after laparoscopic radical gastrectomy for gastric cancer. Conventional treatments such as gastrointestinal decompression, gastric acid suppression therapy and intravenous nutritional support were administrated, but there were no obvious improvements in nausea, vomiting, abdominal distension of this patient. Fu's subcutaneous needling was performed once a day for three days, for a total of three treatments. After three days of Fu's subcutaneous needling intervention, he was free of symptoms of nausea, vomiting and stomach fullness. His gastric drainage volume reduced from 1000 ml per day to 10 ml per day. Upper gastrointestinal angiography showed normal peristalsis of remnant stomach. In this case report, Fu's subcutaneous needling showed a potential role of gastrointestinal motility enhancement and gastric drainage volume decrement, which provided a safe and convenient method in palliative care of postsurgical gastroparesis syndrome.

Invasive acupuncture for gastroparesis after thoracic or abdominal surgery: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis aimed to systematically evaluate the efficacy of acupuncture in treating postsurgical gastroparesis syndrome (PGS) after thoracic or abdominal surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Twelve databases (PubMed, Embase, Cochrane Library Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid) (from 1946), Web of Science, EBSCO, Scopus, Open Grey, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc (CBM)) and three registration websites (WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR)) were searched from the inception to September 2022, and citations of the included literature were screened. ELIGIBILITY CRITERIA: All randomised controlled trials addressing invasive acupuncture for PGS. DATA EXTRACTION AND SYNTHESIS: Key information on the included studies was extracted by two reviewers independently. Risk ratio (RR) with 95% CI was used for categorical data, and mean difference with 95% CI for continuous data. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Outcomes were conducted with trial sequential analysis (TSA). RESULTS: Fifteen studies with 759 patients met the inclusion criteria. Subgroup analyses revealed that compared with the drug group, the drug and acupuncture group had a greater positive effect on the total effective rate (TER) (nine trials, n=427; RR=1.20; 95% CI 1.08 to 1.32; P-heterogeneity=0.20, I2=28%, p=0.0004) and the recovery rate (RCR) (six trials, n = 294; RR = 1.61; 95% CI 1.30 to 1.98; P-heterogeneity=0.29, I2=19%, p<0.0001) of PGS after abdominal surgery. However, acupuncture showed no significant advantages in terms of the TER after thoracic surgery (one trial, p=0.13) or thoracic/abdominal surgery-related PGS (two trials, n = 115; RR=1.18; 95% CI 0.89 to 1.57; P-heterogeneity=0.08, I2=67%, p=0.24) and the RCR after thoracic/abdominal surgery (two trials, n=115; RR=1.40; 95% CI 0.97 to 2.01; P-heterogeneity=0.96, I2=0%, p=0.07). The quality of evidence for TER and RCR was moderate certainty. Only one study reported an acupuncture-related adverse event, in the form of mild local subcutaneous haemorrhage and pain that recovered spontaneously. TSA indicated that outcomes reached a necessary effect size except for clinical symptom score. CONCLUSION: Based on subgroup analysis, compared with the drug treatment, acupuncture combined drug has significant advantages in the treatment of PGS associated with abdominal surgery, but not with thoracic surgery. PROSPERO REGISTRATION NUMBER: CRD42022299189.

Reconsideration of the Gastroparetic Syndrome.

PURPOSE OF REVIEW: Gastroparesis is a chronic disorder characterized by a constellation of foregut symptoms, including postprandial nausea, vomiting, distension, epigastric pain, and regurgitation in the absence of gastric outlet obstruction. Despite considerable research over the past decades, there remains to be only nominal understanding of disease classification, diagnostic criteria, pathogenesis, and preferred therapy. RECENT FINDINGS: We critically reassess current approaches for disease identification and stratification, theories of causation, and treatment for gastroparesis. Gastric scintigraphy, long considered a diagnostic standard, has been re-evaluated in light of evidence showing low sensitivity, whereas newer testing modalities are incompletely validated. Present concepts of pathogenesis do not provide a unified model linking biological impairments with clinical manifestations, whereas available pharmacological and anatomical treatments lack explicit selection criteria or evidence for sustained effectiveness. We propose a disease model that embodies the re-programming of distributed neuro-immune interactions in the gastric wall by inflammatory perturbants. These interactions, combined with effects on the foregut hormonal milieu and brain-gut axis, are postulated to generate the syndromic attributes characteristically linked with gastroparesis. Research linking models of immunopathogenesis with diagnostic and therapeutic paradigms will lead to reclassifications of gastroparesis that guide future trials and technological developments. KEY POINTS: • The term gastroparesis embodies a heterogenous array of symptoms and clinical findings based on a complex assimilation of afferent and efferent mechanisms, gastrointestinal locations, and pathologies. • There currently exists no single test or group of tests with sufficient capacity to be termed a definitional standard for gastroparesis. • Present research regarding pathogenesis suggests the importance of immune regulation of intrinsic oscillatory activity involving myenteric nerves, interstitial cells of Cajal, and smooth muscle cells. • Prokinetic pharmaceuticals remain the mainstay of management, although novel treatments are being studied that are directed to alternative muscle/nerve receptors, electromodulation of the brain-gut axis, and anatomical (endoscopic, surgical) interventions.