RARE DISEASE
Idiopathic gastroparesis
Idiopathic gastroparesis
Idiopathic gastroparesis
Drug discovery
787
papers
On emerging therapies
Overview
Idiopathic gastroparesis is a chronic gastric motility disorder characterized by delayed stomach emptying without mechanical obstruction, presenting with nausea, vomiting, postprandial fullness, and abdominal pain [6][15]. Diagnosis requires exclusion of secondary causes (e.g., diabetes, surgery) and confirmation via gastric emptying studies [1][18]. It is the most common gastroparesis subtype, though its pathophysiology remains unclear, often overlapping with functional dyspepsia [6][15].
Burden
High healthcare utilization: Average inpatient costs reach $7,000/month, with frequent ED visits/hospitalizations [2][4][14].
Significantly impacts quality of life due to chronic symptoms, malnutrition risk, and comorbid anxiety/depression [11][15][19]. Mortality rates exceed the general population, often linked to complications like malnutrition [14][15].
*Domperidone access restricted in the US via FDA IND protocol [3][18].
Therapies
First-line: Dietary modifications (small, low-fiber/low-fat meals), antiemetics (ondansetron), and prokinetics (metoclopramide, domperidone*) [1][3][18].
Refractory cases: Consider endoscopic interventions (G-POEM) or gastric electrical stimulation [1][3][12]. Avoid opioids and GLP-1 agonists due to motility impairment [1][16].
Categories: rare gastroenterological diseases
Research Papers
787 drug discovery papers about Idiopathic gastroparesis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
787 drug discovery papers about Idiopathic gastroparesis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-15 | Increasing Health Care Outcomes of Gastroparesis
In the absence of mechanical blockage, gastroparesis is a disorder characterized by delayed stomach emptying that lasts for at least three months. The symptoms of the condition include bloating, early satiety, nausea, vomiting, and stomach pain. Abnormalities in gastrointestinal motor function, a complicated series of events linked to the parasympathetic and sympathetic nervous systems, gastric smooth muscle cells, pacemaker cells in the stomach and intestine, and the pyloric sphincter, result from delayed or ineffective gastric emptying. Patients with gastroparesis also show changes in cytokine expression and mucosal immune cell infiltration. Over 50% of gastroparesis cases are idiopathic; typical reasons include diabetes, surgery, and infection. The increased prevalence of diabetes, obesity, and the drugs that cause it to have all been linked to an increased incidence of gastroparesis. Clinically, functional dyspepsia and gastroparesis frequently co-occur, and many patients have symptoms that overlap; diagnostic testing is crucial to confirm the existence of gastroparesis. In addition to highlighting the crucial role of the interprofessional healthcare team in promoting patient outcomes along with this gastrointestinal disease process, this activity is precise on the epidemiology, etiology, pathophysiology, evaluation, and therapy of gastroparesis.
2026-06-05 | Gastroparesis: A Comprehensive Overview of Pathophysiology, Etiology, Diagnosis, and Multidisciplinary Management
Gastroparesis is a chronic, often debilitating disorder of gastric motility defined by objectively delayed gastric emptying in the absence of mechanical obstruction, with symptoms persisting for at least three months. The clinical presentation—dominated by nausea, vomiting, early satiety, postprandial fullness, bloating, and abdominal pain—correlates only modestly with the degree of emptying delay, posing a persistent diagnostic challenge. The underlying pathophysiology is multifactorial, involving dysfunction at multiple levels: autonomic (vagal and sympathetic) dysregulation, impaired antral contractility, pyloric sphincter abnormalities, loss of interstitial cells of Cajal (the gastric pacemakers), and, increasingly recognized, localized inflammatory infiltration of the myenteric plexus. The most common etiologies are idiopathic (approximately 50% of cases), followed by diabetic, postsurgical, and postinfectious causes. Diabetic gastroparesis, more frequent and severe in type 1 diabetes, is closely linked to poor glycemic control and other autonomic neuropathies, while postsurgical gastroparesis often results from iatrogenic vagal injury. The incidence has risen markedly over recent decades, paralleling increases in diabetes, obesity, and use of causative medications such as GLP-1 agonists and opioids. Diagnostic evaluation centers on gastric emptying scintigraphy, the gold standard, with the wireless motility capsule and gastric emptying breath test serving as useful alternatives. Treatment requires a holistic, interprofessional approach: dietary modification (small, low-fat, low-fiber meals) forms the foundation; pharmacotherapy is limited, with metoclopramide as the only FDA-approved prokinetic, though its use is constrained by a black box warning for tardive dyskinesia. Off-label agents including domperidone, erythromycin, and antiemetics provide symptomatic relief. For refractory cases, gastric electrical stimulation offers a surgical option, particularly in diabetic patients. Prognosis varies widely by etiology: postinfectious gastroparesis often resolves within 12 months, while diabetic and idiopathic forms tend to be chronic, with significant impacts on quality of life, nutritional status, and healthcare utilization. An interprofessional team—integrating gastroenterologists, dietitians, pharmacists, diabetes educators, and mental health professionals—is essential to optimize outcomes in this challenging patient population.
2026-04-03 | Efficacy and Safety of Domperidone for Patients With Symptoms of Gastroparesis; Long-Term Results.
Domperidone is used to treat refractory symptoms of gastroparesis. There is awareness about the risks and benefits of using domperidone; however, studies have primarily been short-term. To review treatment results with domperidone with focus on long-term efficacy and side effects. Patients with gastroparesis symptoms who entered our FDA IND, IRB-approved domperidone protocol between 2005 and 2025 were treated with oral domperidone 10 mg 3-4 times daily and followed every 2 months for the first year, then every 6 months. Patients completed Patient Assessment of Upper GI Symptoms (PAGI-SYM) and Clinical Patient Grading Assessment Scale (CPGAS; +3 = great deal better, 0 = no change). 827 patients (64% idiopathic, 22% diabetic, 6% postsurgical, 5% atypical) participated; delayed gastric emptying in 86%, normal in 13%, and rapid in 1%. 298 patients have continued domperidone for 7.6 ± 6.4 years with a dose of 36 ± 20 mg per day. The CPGAS benefit score averaged 2.3 ± 0.9 (~"moderately better"). There were improvements in symptoms, particularly nausea, postprandial fullness, and loss of appetite. 529 patients stopped domperidone treatment; lack of efficacy (114 patients), side effects (100), switching to another treatment (42), cost (26), and the remainder lost to follow up. Most common side effects for stopping DOM were palpitations (20 patients), prolonged EKG QTc (13), chest pain (11), diarrhea (10), headache (9), dizziness (8), and lactation (8). In this study of patients treated with long term domperidone for symptoms of gastroparesis, 298 of 827 (36%) patients continued treatment for a mean of 7.6 years with patients reporting being moderately better. Thus, in select patients, domperidone treatment is an effective long-term treatment for symptoms of gastroparesis, able to be safely administered with careful patient monitoring.
2026-03-11 | Progress in Gastroparesis Management: From Pharmacotherapy to Interventional Treatments.
Gastroparesis is a sensorimotor condition characterized by delayed gastric emptying without any obvious mechanical obstruction. Common symptoms include early satiety, nausea, vomiting, belching, and bloating. The most frequent causes of gastroparesis are diabetes, idiopathic factors, and post-surgical complications. Currently, the only FDA-approved medication for treating gastroparesis is metoclopramide; however, due to its potential side effects, particularly extrapyramidal symptoms, there is increasing interest in safer, more tolerable alternatives, such as prokinetics, antiemetics, and fundic relaxants. Recent advancements in pharmacological agents have demonstrated variable efficacy in improving gastric emptying and gastroparesis-related symptoms, although symptom improvement does not consistently correlate with changes in gastric emptying metrics. In addition to pharmacological treatments, non-pharmacological approaches like gastric peroral endoscopic myotomy (G-POEM) and neuromodulation techniques have demonstrated significant improvements in symptoms and gastric emptying. The current understanding of gastroparesis care is still limited, and the best practices in treatment remain uncertain. Future research should prioritize multicenter trials that involve large patient populations to explore emerging therapies and innovative techniques. In this review, we will discuss the existing standards of care, advancements in novel pharmacological, interventional, and neuromodulatory treatments for gastroparesis, as well as their clinical integration, limitations, and prospects.
2025-10-01 | S1198 Clinical Symptom Burden and Overlapping Disorders of Gut–Brain Interaction in Gastroparesis vs Functional Dyspepsia: A Propensity-Matched Cohort Study
Introduction: Gastroparesis (GP) and functional dyspepsia (FD) are chronic gastrointestinal (GI) disorders with overlapping symptoms. GP typically presents with nausea, vomiting, and early satiety, while FD is more often linked to epigastric pain. Whether they are distinct conditions, or a spectrum remains debated. We looked at population-level comparison of symptom profiles and co-existing gut–brain interaction disorders. Methods: We conducted a retrospective cohort study using the TriNetX database, identifying attributes using International Classification of Diseases-10, CPT, and RxNorm codes. Patients with structural gastric or small bowel abnormalities were excluded. GP was defined by diagnosis within 3 months of a gastric emptying study and typical symptoms 3–12 months prior. FD required a diagnosis with prior upper endoscopy (1–12 months) and symptoms 6–12 months before diagnosis. Patients with overlapping GP/FD diagnoses were excluded. Primary outcomes were clinical symptoms; secondary outcomes included co-existing gut–brain interaction disorders. Propensity score matching (1:1) adjusted for demographics and comorbidities. Relative risks (RRs) and 95% CIs were calculated, with P < .05 considered significant. Results: Our study included 7,329 patients with GP (mean age 47.1 ± 17.6 years; 72.7% women) and 3,950 with FD (mean age 44.7 ± 20.3 years; 69.2% women). After 1:1 propensity score matching, 3,420 patients per group were followed for 5 years. Compared to FD, GP patients had greater burden of nausea (RR 1.4, 95% CI 1.28–1.51, P < .0001), vomiting (RR 1.9, 95% CI 1.66–2.18, P < .0001), anorexia (RR 1.3, 95% CI 1.03–1.67, P = .03), early satiety (RR 1.3, 95% CI 1.03–1.66, P = .03), abdominal distension (RR 1.3, 95% CI 1.13–1.37, P < .0001), malnutrition (RR 2.8, 95% CI 2.23–3.42, P < .0001), and weight loss (RR 1.3, 95% CI 1.15–1.53, P < .0001). Epigastric pain was less common in GP (RR 0.6, 95% CI 0.54–0.63, P < .0001). GP was also linked to higher rates of chronic idiopathic constipation (RR 1.7, 95% CI 1.30–2.10, P < .0001) and slow transit constipation (RR 1.5, 95% CI 1.17–1.87, P = .0011), but lower rates of IBS (RR 0.7, 95% CI 0.64–0.77, P < .0001). Conclusion: In this large-scale database study comparing GP and FD, substantial symptom overlap was observed; however, GP was more strongly associated with motility-related symptoms, nutritional complications, and constipation, while FD more commonly with epigastric pain and IBS.
proteins
2025-10-01 | S1149 A Wrinkle in the Plan: Pyloric Botox May Complicate Eventual G-POEM
Introduction: Pyloric directed therapies including pyloric Botox injection or gastric peroral endoscopic myotomy (G-POEM) can benefit some patients with refractory gastroparesis. With the increase in use of G-POEM among these patients, we aim to evaluate how prior pyloric Botox injections may impact G-POEM outcomes. Methods: We conducted a retrospective review of patients who underwent G-POEM at our institution between April 2019 and 2025. We collected demographic information and details of prior treatments including the number of prior Botox injections. G-POEM procedural details collected included total procedure time, time from incision start to closing end, and time spent on tunneling, myotomy, and closing. Patients were grouped based on how many prior Botox injections they had received. Welch’s t-tests were performed to evaluate differences in procedural times between groups. Results: A total of 50 patients underwent G-POEM during our study period. The majority (N = 42, 84.0%) of patients had prior pyloric Botox injections. Of these, most (73.8%) were women and had idiopathic gastroparesis (64.0%). All procedures were technically successful and there were no complications. Patients were divided into 2 groups, those with 0-1 prior pyloric injections and those with at least 2 prior injections. Patients with 2+ prior injections had a significantly longer average total procedure time compared to those with 0-1 (67.94 vs 56.11 minutes respectively, P = 0.040). A total of 35 patients had full procedural timing details available. When comparing groups in this subset, patients with 2+ prior injections had significantly longer procedure components compared to those that had 0-1 prior injections, including longer average closing time (16.16 vs 10.43 minutes, P = 0.01) and longer average time from incision start to closure end (52.60 vs 36.86 minutes, P = 0.001). There was a trend towards significance with the 2+ prior injection group having a longer average tunneling time compared to those with 0-1 injections (21.28 vs 16.14 minutes, P = 0.07). Conclusion: Our results identified a new consideration in the risk-benefit evaluation of pyloric Botox injections in patients with refractory gastroparesis. Among patients undergoing G-POEM, having repeated Botox injections to the pylorus is associated with longer procedural times. We hypothesize that this may be due to increased fibrosis from repeated instrumentation, which then complicates certain aspects of the procedure and overall procedure time.
2025-07-01 | Intra-pyloric botulinum toxin injection improves liquid gastric emptying using 99mTc DTPA scintigraphy: a case report in a 2 years- old girl with idiopathic gastroparesis.
Gastroparesis, characterized by delayed gastric emptying in the absence of mechanical obstruction, is a challenging condition to diagnose and treat in children due to limited pediatric-specific data. This case report presents a 15-month-old girl with recurrent and chronic vomiting since infancy, which worsened upon the introduction of solid foods. Initial diagnostic evaluations, including esophagogastroduodenoscopy (EGD) and upper gastrointestinal contrast study, ruled out structural abnormalities. A gastric emptying scintigraphy (GES) with 99mTc DTPA confirmed significant gastric retention, leading to a diagnosis of idiopathic gastroparesis. Endoscopic intra-pyloric botulinum toxin injection (IPBI) was performed and resulting in significant symptom improvement. Post-procedure assessments revealed improved gastric emptying, with reduced retention at 60 and 180 minutes and a markedly decreased half-time (t1/2) was shown following the procedure. These findings highlight that IPBI may be a promising therapeutic option for pediatric idiopathic gastroparesis unresponsive to standard treatments. Further research is warranted to refine treatment protocols and evaluate long-term outcomes.
2024-10-01 | S2324 Predictive Value of Pyloric Distensibility Measurement for Symptomatic Response After IntrapyloricBotulinumToxin Injection Among Patients With Idiopathic Gastroparesis
Introduction: Gastroparesis is a chronic condition characterized by delayed gastric emptying, leading to symptoms such as nausea, vomiting, early satiety, and abdominal pain. Recent studies indicate that pyloric distensibility, or the ability of the pylorus to stretch, is altered in 30% to 50% of gastroparesis patients, correlating with gastric emptying rates and symptom severity. Intrapyloric botulinum toxin (BT) injection has been proposed to relax the pyloric sphincter and improve gastric emptying, although patient response varies. Identifying predictive markers for symptomatic response is essential to optimize patient selection and treatment outcomes. Methods: Pyloric distensibility was measured in 19 idiopathic gastroparesis patients (mean age: 46.26±22 years) using the EndoFLIP system (Medtronic) post intrapyloric BT injection. Total symptomatic score (TSS) was assessed prospectively before and 3 months after BT injection. Data were analyzed using EndovizX software (Motilitviz, La Jolla, CA) to extract pressure, diameter, and distensibility of the pyloric region from 30cc volume to 10-second point 50cc volume, including mean, standard deviation, minimum, and maximum values. Results: Significant differences were observed between responders (n=7) and non-responders (n=12) (Figure 1). Responders had a significantly higher mean distensibility index (DI; mean DI 12.2 mm2/mm Hg, SD 17.51) compared to non-responders (mean DI 1.57 mm2/mm Hg, SD 1.7), with P-values of 0.024 (1-sided) and 0.048 (2-sided). Maximum DI was also higher in responders (mean 59.28 mm2/mm Hg, SD 76.78) vs non-responders (mean 9.48 mm2/mm Hg, SD 5.09), with P-values of 0.018 (1-sided) and 0.035 (2-sided). Maximum pressure was significantly lower in responders (mean 34.05 mm Hg, SD 19.56) vs non-responders (mean 54.67 mm Hg, SD 19.39), with P-values of 0.02 (1-sided) and 0.04 (2-sided). Maximum diameter showed a near-significant trend, with responders having a larger mean diameter (mean 25.39 mm, SD 13.61) vs non-responders (mean 17.56 mm, SD 3.66), with P-values of 0.036 (1-sided) and 0.073 (2-sided). Conclusion: The significant differences in DI between responders and non-responders suggest that DI could be a key predictor of symptomatic response to intrapyloric BT injection. Further research with larger sample sizes is needed to validate its role in personalized treatment strategies for gastroparesis.Figure 1.: Pyloric diameter in idiopathic gastroparesis patients: responders vs non-responders to pyloric botox injection.
2023-10-01 | S1887 Efficacy of Endoscopic Intrapyloric Injection of Botulinum Toxin in the Treatment of Gastroparesis: A Systematic Review and Meta-Analysis
Introduction: Observational studies suggest symptomatic improvement after intrapyloric injection of Botulinum toxin in treating gastroparesis in an attempt to paralyze the pyloric sphincter complex. However, a limited number of clinical trials failed to demonstrate any benefit to this therapy. We conducted a systematic review and meta-analysis to ascertain the outcomes of intrapyloric injection of Botulinum toxin in the treatment of gastroparesis. Methods: We conducted a comprehensive search of Ovid Cochrane, Ovid Embase, Ovid Medline, Scopus, and Web of Science (inception to September 2022) to identify studies reporting on the use of intrapyloric injection of Botulinum toxin in gastroparesis. The primary outcome was overall clinical success while secondary outcomes were improvement in Gastroparesis Cardinal Symptom Index (GCSI), Gastric Emptying Study (GES); improvement in nausea/vomiting, fullness/distension, and bloating/belching. Clinical success was measured as improvement in either GES or GCSI. A meta-analysis of proportions was done for all primary and secondary outcomes. Results: A total of 8 studies were included. The study consisted of 156 patients including 29 males and 104 females; mean age of 43.6+/-7.4 years. Etiology was diabetes in 35.2% (55/156), idiopathic in 55.2% (86/156) and others in 9.6% (15/156). Overall clinical success was seen in 64.3% of patients (95% CI: 45.7-79.4%; I2 68%). Improvement in GCSI was seen in 60.4% of patients (95% CI: 39.3-78.3%; I2 72%) while improvement in GES was seen in 70.2% (95% CI: 55.0-81.9%; I2 0%). Symptomatic improvement in nausea/vomiting occurred in 25.6% (95% CI: 15.5-39.3%; I2 3%), fullness/distension occurred in 26.9% (95% CI: 2.0-86.7%; I2 85%) and bloating/belching occurred in 31.4% (95% CI: 5.4-78.5 %; I2 83%). Conclusion: Our meta-analysis demonstrates improvement in objective criteria for gastroparesis like GCSI and GES. However, improvement in objective scores did not translate into improvement in subjective symptoms for the patients. The study demonstrates a limited benefit of intrapyloric injection of Botulinum toxin in gastroparesis.
2023-02-07 | Predictors of favorable outcome after pyloroplasty for gastroparesis: should response to pyloric dilation or Botox injection be used as a marker of surgical outcome?
Pyloroplasty and gastric peroral endoscopic myotomy (G-POEM) are effective surgeries for gastroparesis. The primary aim of this study was to evaluate outcomes of pyloroplasty and G-POEM in patients with gastroparesis and determine factors associated with favorable outcome. The secondary aim was to assess the utility of clinical response to preoperative pyloric dilation or botulinum toxin injection (Botox) on surgical outcome, a factor conventionally used as a favorable marker.There were 204 patients who underwent pyloroplasty (n = 177) or G-POEM (n = 27) for gastroparesis at our institution from 2014 to 2021. Demographic and clinical parameters were analyzed to assess their impact on surgical outcome. A subgroup of patients who had pyloric dilation or Botox injection were assessed separately. Favorable outcome was defined as patient reported complete resolution of the predominant gastroparesis symptom.Favorable outcome was achieved in 78.4% of patients (pyloroplasty: 79.7% and G-POEM: 70.4%, p = 0.274). Among 61 patients where pre- and postoperative gastric emptying studies (GES) were available, mean 4-hour retention significantly improved from 33.5 to 15.0% (p < 0.001) and 77.0% of patients achieved normalization. Favorable outcome was not significantly impacted by etiology of gastroparesis (p = 0.120), GERD (p = 0.518), or primary gastroparesis symptom (p = 0.244). Age ≥ 40 was a significant predictor of favorable surgical outcome on multivariate analysis [OR: 2.476 (1.224-5.008), p = 0.012]. Among the patients who had preoperative dilation (n = 82) or Botox injection (n = 46), response to these interventions was not a predictor of favorable surgical outcome (p = 0.192 and 0.979, respectively). However, preoperative Botox injection, regardless of response to injection, was associated with favorable surgical outcome [OR: 3.205 (CI 1.105-9.299), p = 0.032].Symptomatic improvement after pyloroplasty or G-POEM is independent of etiology of gastroparesis, GERD, and primary symptom. Response to dilation or Botox are not markers of response to surgery. However, patients who receive Botox are 3.2 times more likely to improve postoperatively.
antibodies
2023-05-01 | The role of M1 to M2 macrophage polarization in the etiology of idiopathic gastroparesis: GWAS perspective
Abstract Gastroparesis is a serious medical condition characterized by delayed gastric emptying. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system is likely central to the pathogenesis of gastroparesis. We have done a GWAS comparing idiopathic and diabetic cases with controls as well as contrasting idiopathic versus diabetic cases. We report a novel genetic association of SLC15A4 locus with idiopathic gastroparesis. This signal is driven by multiple variants with top missense variant SLC15A4:NM145648:exon2:c.T716C:p.V239A, rs33990080. Altogether, among EUR cohort we report 69 carriers out of 214 versus controls 165 out of 896 (MAF: cases 0.18; MAF: controls 0.09) and OR: 1.9 (p-value logistic model 10^−6). The significant effect persists when idiopathic cases are compared with diabetic cases as the MAF of diabetic cases (0.10) is comparable to that of population controls (0.09). Solute carrier family 15 (SLC15) A4 is a lysosome-resident amino acid/oligopeptide transporter that is preferentially expressed in immune cells. It is required for TLR7/9-dependent type I interferon production and plays a critical role in the pathogenesis of lupus and colitis. SLC15A4 was shown to mediate M1-prone metabolic shifts in macrophages and guards immune cells from metabolic stress. Previous reports have shown that when the anti-inflammatory M2 macrophages are switched to pro-inflammatory M1 macrophages, delayed GE was evident in animal models. Current genetic findings suggest that a mechanism directly connected to macrophage polarization may be implicated in a subset of idiopathic gastroparesis patients.
2014-12-20 | Future Directions in the Treatment of Gastroparesis
Understanding of gastroparesis is evolving, in part because of systematic studies on the pathology, pathophysiology, and outcomes. It is clear that simply accelerating gastric emptying may not effectively control symptoms in this syndrome and more creative approaches are required that address aberrant sensation (vagal and spinal) as well as regional disturbances in motility. Further, with the growing recognition of a possible inflammatory basis, the prospects of disease modifying now seem realistic.
2014-07-13 | Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis.
Abstract Background There is increasing evidence for specific cellular changes in the stomach of patients with diabetic ( DG ) and idiopathic ( IG ) gastroparesis. The most significant findings are loss of interstitial cells of Cajal ( ICC ), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD 206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD 206+ and i NOS + cells. To investigate associations between cellular phenotypes and ICC . Methods Full thickness gastric body biopsies were obtained from non‐diabetic controls (C), diabetic controls ( DC ), DG , and IG patients. Sections were labeled for CD 45, CD 206, Kit, i NOS , and putative human macrophage markers ( HAM 56, CD 68, and EMR 1). Immunoreactive cells were quantified from the circular muscle layer. Key Results Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD 206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between i NOS + cells and ICC in the DC group, but not the other groups. CD 68 and HAM 56 reliably labeled the same cell populations, but EMR 1 labeled other cell types. Conclusions & Inferences Depletion of ICC and correlation with changes in CD 206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD 206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages.
2006-05-12 | 13 Role of local progenitors in the sustenance of networks of interstitial cells of Cajal (ICC) in the murine stomach
Depletion of ICC networks and consequent changes in electrical slow wave activity and neuromuscular neurotransmission play important roles in diabetic and idiopathic gastroparesis. We have shown that reduced insulin/IGF‐I signaling and consequent decrease in stem cell factor (SCF) production underlie the ICC depletion of diabetic gastroparesis. It is, however, unclear whether the ICC loss is caused primarily by the accelerated attrition of mature cells or their impaired regeneration. In this study we identified local ICC progenitors and studied their role in the sustenance of gastric ICC networks. We investigated the expression of CD34, a putative marker for ICC precursors, and receptors for SCF (Kit), insulin, and IGF‐I in murine gastric muscles by flow cytometry and immunohistochemistry. In freshly dissected tissues, CD34 was not detected in Kit Bright ICC but a small population of Kit Low cells expressed high levels of CD34. These cells were oval‐shaped, had no processes, and occurred in small clusters on the serosal and submucosal surfaces of the gastric musculature and in the myenteric region. Unlike mature ICC, they expressed insulin and IGF‐I receptors. Kit Low CD34 + cells were undetectable and Kit + ICC were profoundly reduced in gastric muscles cultured in the absence of growth factors for up to 85 days. Soluble SCF added to the culture media for 32–85 days rescued Kit Low CD34 + cells and caused their growth into densely packed clusters in the myenteric region or thick chords containing bipolar cells within the muscle layers. These cells had elevated Kit and reduced CD34 expression. Cultures treated in a similar manner with IGF‐I to stimulate both soluble and membrane‐bound SCF were dominated by normal, Kit + CD34 – ICC networks. IGF‐I treatments were only effective when initiated within the first 2–4 weeks of culturing, although mature, Kit + ICC were able to survive longer. In adult H‐2K b ‐tsA58 mice harbouring the temperature‐sensitive large tumour antigen encoded by a mutant strain of simian virus 40, stimulating cell proliferation by culturing at 33°C prevented the decline of gastric ICC even in the absence of exogenous growth factors. We conclude that maintenance of gastric ICC probably involves their regeneration from rare Kit Low CD34 + precursors that depend on a nearly uninterrupted supply of insulin or IGF‐I. While the development of these cells into ICC can be initiated with soluble SCF, their expansion and conversion into mature, CD34 – ICC also requires membrane‐bound SCF. Supported by NIH Grants DK58185 and RR16464.
cell therapies
2026-06-01 | Achieving Symptom Control in the Treatment of Gastroparesis: From Pills to Pacing
Abstract Background Gastroparesis is a chronic disorder of the stomach characterized by delayed emptying without mechanical obstruction. Affected patients experience nausea, vomiting, and a feeling of fullness. Achieving sufficient symptom control remains challenging. Aims The aim of this retrospective study was to analyse the use and effectiveness of current treatment options employed in a step-up approach: 1.Dietary changes, 2.pharmacological treatment (prokinetic drugs including domperidone and prucalopride, and laxatives), 3.pyloric interventions (endoscopic balloon dilation, gastric per-oral endoscopic myotomy (G-POEM), laparoscopic surgical pyloromyotomy), and 4.gastric electrical stimulation (GES, EnterraTM). Methods All patients treated for gastroparesis at a tertiary hospital by a dedicated team between 01/2025 and 01/2026 were included. Diagnosis was confirmed by gastric emptying scintigraphy. Exclusion criteria were previous upper gastrointestinal tract surgery, concomitant hiatal hernia or gastroesophageal reflux disease (GERD), and intestinal failure. Main outcome was sufficient symptom control at the latest available follow-up defined as improved or contained symptoms without need for treatment escalation. Results Fifty patients were included. Median age was 39 years (IQR 25-57), 66% were female. Reasons for gastroparesis was idiopathic in 80%, diabetes in 8%, and rheumatologic or neurologic disease in 12%. Most frequent symptoms were feeling of fullness (82%) and nausea (74%). Sufficient symptom control following conservative treatment was achieved in 13 patients (26%). Eighteen patients (36%) underwent at least one pyloric intervention [G-POEM (n=5), dilatation (n=10), laparoscopic pyloromyotomy (n=5)], with five patients (10%) achieving sufficient symptom control. Fifteen patients (30%) received a GES device, of which two-thirds (n=10) achieved sufficient symptom control. Twenty patients (40%) had at least two interventions during their treatment course. Conclusion Adequate symptom control often requires escalation beyond conservative treatment. Many patients need multiple interventions, emphasizing the chronic nature of gastroparesis. These findings highlight the importance of an individualized, multimodal treatment approach and the need to further investigate predictors of treatment response.
2025-10-01 | S1112 Efficacy and Safety of Bioelectrical Therapies for Gastrointestinal Motility Disorders: A Systematic Review and Meta-Analysis
Introduction: Gastrointestinal motility disorders, such as gastroparesis, significantly impair quality of life, with limited effective treatments for refractory cases. Bioelectrical therapies, including gastric electrical stimulation (GES) and combined approaches with pyloric procedures, have been studied as promising interventions. This systematic review and meta-analysis evaluates their efficacy and safety in managing symptoms of gastroparesis and related disorders. Methods: We systematically searched databases for studies (randomized controlled trials, cohort studies, and observational studies) on bioelectrical therapies (GES, GES with pyloroplasty, gastric peroral endoscopic myotomy) in patients with gastroparesis or similar motility disorders. Eligible studies (n = 15) included 1,487 patients, with data on age (range 2–84 years), sex (61.8%–89.4% female), and etiologies (diabetic, idiopathic, postsurgical). Primary outcomes were changes in symptom severity (Gastroparesis Cardinal Symptom Index [GCSI] score), with secondary outcomes including gastric emptying time, quality of life (QoL), hospital admissions, and adverse events. Data were pooled using standardized mean differences and risk ratios, with heterogeneity assessed via I² statistics. Results: Bioelectrical therapies, particularly GES, significantly reduced symptom severity (pooled GCSI score reduction: 1.2–2.5 points, 10 studies) across diverse cohorts. Combined GES and pyloric procedures showed comparable or superior outcomes, especially in diabetic and idiopathic gastroparesis. Gastric emptying improved in 60% of studies (4-hour retention decrease: 10%–30%). Quality of life scores (GIQLI) and hospital admission rates also improved, though adverse events (e.g., device migration, infection) occurred in 5%–15% of cases. Heterogeneity was moderate (I² = 45%–60%), reflecting variability in study design, stimulation parameters, and follow-up (6 months–17 years). Conclusion: Bioelectrical therapies, combined with pyloric interventions, demonstrate promising efficacy in symptom control for gastrointestinal motility disorders, with acceptable safety profiles. However, variability in protocols and study designs highlights the need for standardized, randomized trials to optimize treatment strategies and patient selection.
2025-01-11 | [Gastric electrostimulation in refractory gastroparesis: results of a explorative observational study].
High-frequency electrical stimulation therapy (gastric electrical stimulation, GES) is a treatment option for gastroparesis of various genesis. The best indication and prognostic parameters have not yet been conclusively determined.Retrospective analysis of all gastroparesis patients implanted with a GES device between 2011 and 2020. Clinical response was measured before and after implantation using a validated Gastroparesis Cardinal Symptom Index (GCSI) (maximum score: 5, minimum score: 0). Other study endpoints included: subjective symptom course (no improvement, partial improvement, or severe improvement) and change in gastroparesis medication.A GES device was implanted in 42 patients (16 M: 26 F, mean age 45 years). The etiology of gastroparesis was diabetic (n=23), idiopathic (n=10) or postoperative (n=9). Eleven patients (26%) had undergone one or more invasive treatments before. GCSI score of the total group was 3.23 preoperatively. The median follow-up time was 12 months. In the overall group, significant improvement in GCSI score was found 3, 6, 9, and 12 months postoperatively-regardless of indication. In multivariate analysis, disease duration of >30 months was associated with a significantly decreased GCSI score at 12 months (p<0.001). Approximately 40% of patients were able to discontinue or significantly reduce gastroparesis medication. At the end of follow-up, 81% of patients reported partial or major improvement in symptoms. During the follow-up period, three patients (7%) died.Gastric electrical neurostimulation is an effective and safe option for refractory gastroparesis-regardless of the underlying disease.
2024-06-12 | Optimal Parameters for Gastric Electrical Stimulation Therapy for Long-Term Symptom Control in Patients with Gastroparesis
Background: Gastric electrical stimulation (GES) therapy is indicated for the treatment of drug-refractory gastroparesis (GP). However, the long-term effects of GES therapy on GP symptom control and identification of the optimal parameters to activate this long-term efficacy have not been investigated. Methods: We conducted a retrospective cohort analysis of 57 GP patients who received GES and pyloroplasty (PP). The interrogation of the GES system and assessment of GP symptoms were conducted at the initiation of GES therapy and during follow-up visits. We determined the changes in GES parameters including voltage (V), impedance (I), and current (C). The outcome was total symptom score (TSS), which was measured by self-reported GP symptoms. Results: The mean age of patients was 44 (±14) years, and 72% were females. The etiology for GP was diabetes mellitus in 72% and idiopathic in 28%. The median duration of GES follow-up was 47 months (range 5–73) A significant decrease was found in individual symptom scores and the TSS (−10.8; 95%CI: −12.6, −9.08) compared to baseline scores (p < 0.0001). During follow-up, readings for I (515 vs. 598 Ω), V (3.3 vs. 4.8 V), and C (6.5 vs. 8.4 mA) significantly increased (p ≤ 0.0001 for all parameters). Higher GES settings were associated with lower TSS in the adjusted analysis (RC, −1.97; 95%CI: −3.81, −0.12, p = 0.037). Conclusions: these findings suggest that adjusting GES parameters over time based on optimizing symptom improvement should be incorporated into the long-term care of patients receiving gastric neurostimulation therapy.
2023-01-06 | Endoscopic mucosal electrodes: New directions for recording and regulating gastric myoelectric activity
With the gradual deepening of the study of gastric motility disorders, people increasingly realize that gastric myoelectric activity plays an important role in coordinating gastric function. This article introduces the advantages of endoscopic mucosal electrodes compared with traditional electrodes. Several different types of mucosal electrodes and how to fix the electrodes by endoscope are introduced. Endoscopic mucosal electrodes can record and regulate gastric myoelectric activity, which has great value in the study of gastric motility. Endoscopic mucosal electrode technique refers to the fixation of the electrode in the designated part of the gastric mucosa by endoscope. Through endoscopic mucosal electrodes, on the one hand, we can record gastric myoelectric activity, on the other hand, we can carry out gastric electrical stimulation to interfere with gastric rhythm. Endoscopic mucosal electrodes have higher accuracy than traditional cutaneous electrodes, less trauma and lower cost than serosal electrodes. Endoscopic mucosal electrodes have a good application prospect for diseases such as gastroparesis and obesity.
small molecules
2026-09-15 | Increasing Health Care Outcomes of Gastroparesis
In the absence of mechanical blockage, gastroparesis is a disorder characterized by delayed stomach emptying that lasts for at least three months. The symptoms of the condition include bloating, early satiety, nausea, vomiting, and stomach pain. Abnormalities in gastrointestinal motor function, a complicated series of events linked to the parasympathetic and sympathetic nervous systems, gastric smooth muscle cells, pacemaker cells in the stomach and intestine, and the pyloric sphincter, result from delayed or ineffective gastric emptying. Patients with gastroparesis also show changes in cytokine expression and mucosal immune cell infiltration. Over 50% of gastroparesis cases are idiopathic; typical reasons include diabetes, surgery, and infection. The increased prevalence of diabetes, obesity, and the drugs that cause it to have all been linked to an increased incidence of gastroparesis. Clinically, functional dyspepsia and gastroparesis frequently co-occur, and many patients have symptoms that overlap; diagnostic testing is crucial to confirm the existence of gastroparesis. In addition to highlighting the crucial role of the interprofessional healthcare team in promoting patient outcomes along with this gastrointestinal disease process, this activity is precise on the epidemiology, etiology, pathophysiology, evaluation, and therapy of gastroparesis.
2026-06-05 | Gastroparesis: A Comprehensive Overview of Pathophysiology, Etiology, Diagnosis, and Multidisciplinary Management
Gastroparesis is a chronic, often debilitating disorder of gastric motility defined by objectively delayed gastric emptying in the absence of mechanical obstruction, with symptoms persisting for at least three months. The clinical presentation—dominated by nausea, vomiting, early satiety, postprandial fullness, bloating, and abdominal pain—correlates only modestly with the degree of emptying delay, posing a persistent diagnostic challenge. The underlying pathophysiology is multifactorial, involving dysfunction at multiple levels: autonomic (vagal and sympathetic) dysregulation, impaired antral contractility, pyloric sphincter abnormalities, loss of interstitial cells of Cajal (the gastric pacemakers), and, increasingly recognized, localized inflammatory infiltration of the myenteric plexus. The most common etiologies are idiopathic (approximately 50% of cases), followed by diabetic, postsurgical, and postinfectious causes. Diabetic gastroparesis, more frequent and severe in type 1 diabetes, is closely linked to poor glycemic control and other autonomic neuropathies, while postsurgical gastroparesis often results from iatrogenic vagal injury. The incidence has risen markedly over recent decades, paralleling increases in diabetes, obesity, and use of causative medications such as GLP-1 agonists and opioids. Diagnostic evaluation centers on gastric emptying scintigraphy, the gold standard, with the wireless motility capsule and gastric emptying breath test serving as useful alternatives. Treatment requires a holistic, interprofessional approach: dietary modification (small, low-fat, low-fiber meals) forms the foundation; pharmacotherapy is limited, with metoclopramide as the only FDA-approved prokinetic, though its use is constrained by a black box warning for tardive dyskinesia. Off-label agents including domperidone, erythromycin, and antiemetics provide symptomatic relief. For refractory cases, gastric electrical stimulation offers a surgical option, particularly in diabetic patients. Prognosis varies widely by etiology: postinfectious gastroparesis often resolves within 12 months, while diabetic and idiopathic forms tend to be chronic, with significant impacts on quality of life, nutritional status, and healthcare utilization. An interprofessional team—integrating gastroenterologists, dietitians, pharmacists, diabetes educators, and mental health professionals—is essential to optimize outcomes in this challenging patient population.
2026-04-03 | Efficacy and Safety of Domperidone for Patients With Symptoms of Gastroparesis; Long-Term Results.
Domperidone is used to treat refractory symptoms of gastroparesis. There is awareness about the risks and benefits of using domperidone; however, studies have primarily been short-term. To review treatment results with domperidone with focus on long-term efficacy and side effects. Patients with gastroparesis symptoms who entered our FDA IND, IRB-approved domperidone protocol between 2005 and 2025 were treated with oral domperidone 10 mg 3-4 times daily and followed every 2 months for the first year, then every 6 months. Patients completed Patient Assessment of Upper GI Symptoms (PAGI-SYM) and Clinical Patient Grading Assessment Scale (CPGAS; +3 = great deal better, 0 = no change). 827 patients (64% idiopathic, 22% diabetic, 6% postsurgical, 5% atypical) participated; delayed gastric emptying in 86%, normal in 13%, and rapid in 1%. 298 patients have continued domperidone for 7.6 ± 6.4 years with a dose of 36 ± 20 mg per day. The CPGAS benefit score averaged 2.3 ± 0.9 (~"moderately better"). There were improvements in symptoms, particularly nausea, postprandial fullness, and loss of appetite. 529 patients stopped domperidone treatment; lack of efficacy (114 patients), side effects (100), switching to another treatment (42), cost (26), and the remainder lost to follow up. Most common side effects for stopping DOM were palpitations (20 patients), prolonged EKG QTc (13), chest pain (11), diarrhea (10), headache (9), dizziness (8), and lactation (8). In this study of patients treated with long term domperidone for symptoms of gastroparesis, 298 of 827 (36%) patients continued treatment for a mean of 7.6 years with patients reporting being moderately better. Thus, in select patients, domperidone treatment is an effective long-term treatment for symptoms of gastroparesis, able to be safely administered with careful patient monitoring.
2026-03-11 | Progress in Gastroparesis Management: From Pharmacotherapy to Interventional Treatments.
Gastroparesis is a sensorimotor condition characterized by delayed gastric emptying without any obvious mechanical obstruction. Common symptoms include early satiety, nausea, vomiting, belching, and bloating. The most frequent causes of gastroparesis are diabetes, idiopathic factors, and post-surgical complications. Currently, the only FDA-approved medication for treating gastroparesis is metoclopramide; however, due to its potential side effects, particularly extrapyramidal symptoms, there is increasing interest in safer, more tolerable alternatives, such as prokinetics, antiemetics, and fundic relaxants. Recent advancements in pharmacological agents have demonstrated variable efficacy in improving gastric emptying and gastroparesis-related symptoms, although symptom improvement does not consistently correlate with changes in gastric emptying metrics. In addition to pharmacological treatments, non-pharmacological approaches like gastric peroral endoscopic myotomy (G-POEM) and neuromodulation techniques have demonstrated significant improvements in symptoms and gastric emptying. The current understanding of gastroparesis care is still limited, and the best practices in treatment remain uncertain. Future research should prioritize multicenter trials that involve large patient populations to explore emerging therapies and innovative techniques. In this review, we will discuss the existing standards of care, advancements in novel pharmacological, interventional, and neuromodulatory treatments for gastroparesis, as well as their clinical integration, limitations, and prospects.
2025-10-01 | S1198 Clinical Symptom Burden and Overlapping Disorders of Gut–Brain Interaction in Gastroparesis vs Functional Dyspepsia: A Propensity-Matched Cohort Study
Introduction: Gastroparesis (GP) and functional dyspepsia (FD) are chronic gastrointestinal (GI) disorders with overlapping symptoms. GP typically presents with nausea, vomiting, and early satiety, while FD is more often linked to epigastric pain. Whether they are distinct conditions, or a spectrum remains debated. We looked at population-level comparison of symptom profiles and co-existing gut–brain interaction disorders. Methods: We conducted a retrospective cohort study using the TriNetX database, identifying attributes using International Classification of Diseases-10, CPT, and RxNorm codes. Patients with structural gastric or small bowel abnormalities were excluded. GP was defined by diagnosis within 3 months of a gastric emptying study and typical symptoms 3–12 months prior. FD required a diagnosis with prior upper endoscopy (1–12 months) and symptoms 6–12 months before diagnosis. Patients with overlapping GP/FD diagnoses were excluded. Primary outcomes were clinical symptoms; secondary outcomes included co-existing gut–brain interaction disorders. Propensity score matching (1:1) adjusted for demographics and comorbidities. Relative risks (RRs) and 95% CIs were calculated, with P < .05 considered significant. Results: Our study included 7,329 patients with GP (mean age 47.1 ± 17.6 years; 72.7% women) and 3,950 with FD (mean age 44.7 ± 20.3 years; 69.2% women). After 1:1 propensity score matching, 3,420 patients per group were followed for 5 years. Compared to FD, GP patients had greater burden of nausea (RR 1.4, 95% CI 1.28–1.51, P < .0001), vomiting (RR 1.9, 95% CI 1.66–2.18, P < .0001), anorexia (RR 1.3, 95% CI 1.03–1.67, P = .03), early satiety (RR 1.3, 95% CI 1.03–1.66, P = .03), abdominal distension (RR 1.3, 95% CI 1.13–1.37, P < .0001), malnutrition (RR 2.8, 95% CI 2.23–3.42, P < .0001), and weight loss (RR 1.3, 95% CI 1.15–1.53, P < .0001). Epigastric pain was less common in GP (RR 0.6, 95% CI 0.54–0.63, P < .0001). GP was also linked to higher rates of chronic idiopathic constipation (RR 1.7, 95% CI 1.30–2.10, P < .0001) and slow transit constipation (RR 1.5, 95% CI 1.17–1.87, P = .0011), but lower rates of IBS (RR 0.7, 95% CI 0.64–0.77, P < .0001). Conclusion: In this large-scale database study comparing GP and FD, substantial symptom overlap was observed; however, GP was more strongly associated with motility-related symptoms, nutritional complications, and constipation, while FD more commonly with epigastric pain and IBS.
proteins
2025-10-01 | S1149 A Wrinkle in the Plan: Pyloric Botox May Complicate Eventual G-POEM
Introduction: Pyloric directed therapies including pyloric Botox injection or gastric peroral endoscopic myotomy (G-POEM) can benefit some patients with refractory gastroparesis. With the increase in use of G-POEM among these patients, we aim to evaluate how prior pyloric Botox injections may impact G-POEM outcomes. Methods: We conducted a retrospective review of patients who underwent G-POEM at our institution between April 2019 and 2025. We collected demographic information and details of prior treatments including the number of prior Botox injections. G-POEM procedural details collected included total procedure time, time from incision start to closing end, and time spent on tunneling, myotomy, and closing. Patients were grouped based on how many prior Botox injections they had received. Welch’s t-tests were performed to evaluate differences in procedural times between groups. Results: A total of 50 patients underwent G-POEM during our study period. The majority (N = 42, 84.0%) of patients had prior pyloric Botox injections. Of these, most (73.8%) were women and had idiopathic gastroparesis (64.0%). All procedures were technically successful and there were no complications. Patients were divided into 2 groups, those with 0-1 prior pyloric injections and those with at least 2 prior injections. Patients with 2+ prior injections had a significantly longer average total procedure time compared to those with 0-1 (67.94 vs 56.11 minutes respectively, P = 0.040). A total of 35 patients had full procedural timing details available. When comparing groups in this subset, patients with 2+ prior injections had significantly longer procedure components compared to those that had 0-1 prior injections, including longer average closing time (16.16 vs 10.43 minutes, P = 0.01) and longer average time from incision start to closure end (52.60 vs 36.86 minutes, P = 0.001). There was a trend towards significance with the 2+ prior injection group having a longer average tunneling time compared to those with 0-1 injections (21.28 vs 16.14 minutes, P = 0.07). Conclusion: Our results identified a new consideration in the risk-benefit evaluation of pyloric Botox injections in patients with refractory gastroparesis. Among patients undergoing G-POEM, having repeated Botox injections to the pylorus is associated with longer procedural times. We hypothesize that this may be due to increased fibrosis from repeated instrumentation, which then complicates certain aspects of the procedure and overall procedure time.
2025-07-01 | Intra-pyloric botulinum toxin injection improves liquid gastric emptying using 99mTc DTPA scintigraphy: a case report in a 2 years- old girl with idiopathic gastroparesis.
Gastroparesis, characterized by delayed gastric emptying in the absence of mechanical obstruction, is a challenging condition to diagnose and treat in children due to limited pediatric-specific data. This case report presents a 15-month-old girl with recurrent and chronic vomiting since infancy, which worsened upon the introduction of solid foods. Initial diagnostic evaluations, including esophagogastroduodenoscopy (EGD) and upper gastrointestinal contrast study, ruled out structural abnormalities. A gastric emptying scintigraphy (GES) with 99mTc DTPA confirmed significant gastric retention, leading to a diagnosis of idiopathic gastroparesis. Endoscopic intra-pyloric botulinum toxin injection (IPBI) was performed and resulting in significant symptom improvement. Post-procedure assessments revealed improved gastric emptying, with reduced retention at 60 and 180 minutes and a markedly decreased half-time (t1/2) was shown following the procedure. These findings highlight that IPBI may be a promising therapeutic option for pediatric idiopathic gastroparesis unresponsive to standard treatments. Further research is warranted to refine treatment protocols and evaluate long-term outcomes.
2024-10-01 | S2324 Predictive Value of Pyloric Distensibility Measurement for Symptomatic Response After IntrapyloricBotulinumToxin Injection Among Patients With Idiopathic Gastroparesis
Introduction: Gastroparesis is a chronic condition characterized by delayed gastric emptying, leading to symptoms such as nausea, vomiting, early satiety, and abdominal pain. Recent studies indicate that pyloric distensibility, or the ability of the pylorus to stretch, is altered in 30% to 50% of gastroparesis patients, correlating with gastric emptying rates and symptom severity. Intrapyloric botulinum toxin (BT) injection has been proposed to relax the pyloric sphincter and improve gastric emptying, although patient response varies. Identifying predictive markers for symptomatic response is essential to optimize patient selection and treatment outcomes. Methods: Pyloric distensibility was measured in 19 idiopathic gastroparesis patients (mean age: 46.26±22 years) using the EndoFLIP system (Medtronic) post intrapyloric BT injection. Total symptomatic score (TSS) was assessed prospectively before and 3 months after BT injection. Data were analyzed using EndovizX software (Motilitviz, La Jolla, CA) to extract pressure, diameter, and distensibility of the pyloric region from 30cc volume to 10-second point 50cc volume, including mean, standard deviation, minimum, and maximum values. Results: Significant differences were observed between responders (n=7) and non-responders (n=12) (Figure 1). Responders had a significantly higher mean distensibility index (DI; mean DI 12.2 mm2/mm Hg, SD 17.51) compared to non-responders (mean DI 1.57 mm2/mm Hg, SD 1.7), with P-values of 0.024 (1-sided) and 0.048 (2-sided). Maximum DI was also higher in responders (mean 59.28 mm2/mm Hg, SD 76.78) vs non-responders (mean 9.48 mm2/mm Hg, SD 5.09), with P-values of 0.018 (1-sided) and 0.035 (2-sided). Maximum pressure was significantly lower in responders (mean 34.05 mm Hg, SD 19.56) vs non-responders (mean 54.67 mm Hg, SD 19.39), with P-values of 0.02 (1-sided) and 0.04 (2-sided). Maximum diameter showed a near-significant trend, with responders having a larger mean diameter (mean 25.39 mm, SD 13.61) vs non-responders (mean 17.56 mm, SD 3.66), with P-values of 0.036 (1-sided) and 0.073 (2-sided). Conclusion: The significant differences in DI between responders and non-responders suggest that DI could be a key predictor of symptomatic response to intrapyloric BT injection. Further research with larger sample sizes is needed to validate its role in personalized treatment strategies for gastroparesis.Figure 1.: Pyloric diameter in idiopathic gastroparesis patients: responders vs non-responders to pyloric botox injection.
2023-10-01 | S1887 Efficacy of Endoscopic Intrapyloric Injection of Botulinum Toxin in the Treatment of Gastroparesis: A Systematic Review and Meta-Analysis
Introduction: Observational studies suggest symptomatic improvement after intrapyloric injection of Botulinum toxin in treating gastroparesis in an attempt to paralyze the pyloric sphincter complex. However, a limited number of clinical trials failed to demonstrate any benefit to this therapy. We conducted a systematic review and meta-analysis to ascertain the outcomes of intrapyloric injection of Botulinum toxin in the treatment of gastroparesis. Methods: We conducted a comprehensive search of Ovid Cochrane, Ovid Embase, Ovid Medline, Scopus, and Web of Science (inception to September 2022) to identify studies reporting on the use of intrapyloric injection of Botulinum toxin in gastroparesis. The primary outcome was overall clinical success while secondary outcomes were improvement in Gastroparesis Cardinal Symptom Index (GCSI), Gastric Emptying Study (GES); improvement in nausea/vomiting, fullness/distension, and bloating/belching. Clinical success was measured as improvement in either GES or GCSI. A meta-analysis of proportions was done for all primary and secondary outcomes. Results: A total of 8 studies were included. The study consisted of 156 patients including 29 males and 104 females; mean age of 43.6+/-7.4 years. Etiology was diabetes in 35.2% (55/156), idiopathic in 55.2% (86/156) and others in 9.6% (15/156). Overall clinical success was seen in 64.3% of patients (95% CI: 45.7-79.4%; I2 68%). Improvement in GCSI was seen in 60.4% of patients (95% CI: 39.3-78.3%; I2 72%) while improvement in GES was seen in 70.2% (95% CI: 55.0-81.9%; I2 0%). Symptomatic improvement in nausea/vomiting occurred in 25.6% (95% CI: 15.5-39.3%; I2 3%), fullness/distension occurred in 26.9% (95% CI: 2.0-86.7%; I2 85%) and bloating/belching occurred in 31.4% (95% CI: 5.4-78.5 %; I2 83%). Conclusion: Our meta-analysis demonstrates improvement in objective criteria for gastroparesis like GCSI and GES. However, improvement in objective scores did not translate into improvement in subjective symptoms for the patients. The study demonstrates a limited benefit of intrapyloric injection of Botulinum toxin in gastroparesis.
2023-02-07 | Predictors of favorable outcome after pyloroplasty for gastroparesis: should response to pyloric dilation or Botox injection be used as a marker of surgical outcome?
Pyloroplasty and gastric peroral endoscopic myotomy (G-POEM) are effective surgeries for gastroparesis. The primary aim of this study was to evaluate outcomes of pyloroplasty and G-POEM in patients with gastroparesis and determine factors associated with favorable outcome. The secondary aim was to assess the utility of clinical response to preoperative pyloric dilation or botulinum toxin injection (Botox) on surgical outcome, a factor conventionally used as a favorable marker.There were 204 patients who underwent pyloroplasty (n = 177) or G-POEM (n = 27) for gastroparesis at our institution from 2014 to 2021. Demographic and clinical parameters were analyzed to assess their impact on surgical outcome. A subgroup of patients who had pyloric dilation or Botox injection were assessed separately. Favorable outcome was defined as patient reported complete resolution of the predominant gastroparesis symptom.Favorable outcome was achieved in 78.4% of patients (pyloroplasty: 79.7% and G-POEM: 70.4%, p = 0.274). Among 61 patients where pre- and postoperative gastric emptying studies (GES) were available, mean 4-hour retention significantly improved from 33.5 to 15.0% (p < 0.001) and 77.0% of patients achieved normalization. Favorable outcome was not significantly impacted by etiology of gastroparesis (p = 0.120), GERD (p = 0.518), or primary gastroparesis symptom (p = 0.244). Age ≥ 40 was a significant predictor of favorable surgical outcome on multivariate analysis [OR: 2.476 (1.224-5.008), p = 0.012]. Among the patients who had preoperative dilation (n = 82) or Botox injection (n = 46), response to these interventions was not a predictor of favorable surgical outcome (p = 0.192 and 0.979, respectively). However, preoperative Botox injection, regardless of response to injection, was associated with favorable surgical outcome [OR: 3.205 (CI 1.105-9.299), p = 0.032].Symptomatic improvement after pyloroplasty or G-POEM is independent of etiology of gastroparesis, GERD, and primary symptom. Response to dilation or Botox are not markers of response to surgery. However, patients who receive Botox are 3.2 times more likely to improve postoperatively.
antibodies
2023-05-01 | The role of M1 to M2 macrophage polarization in the etiology of idiopathic gastroparesis: GWAS perspective
Abstract Gastroparesis is a serious medical condition characterized by delayed gastric emptying. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system is likely central to the pathogenesis of gastroparesis. We have done a GWAS comparing idiopathic and diabetic cases with controls as well as contrasting idiopathic versus diabetic cases. We report a novel genetic association of SLC15A4 locus with idiopathic gastroparesis. This signal is driven by multiple variants with top missense variant SLC15A4:NM145648:exon2:c.T716C:p.V239A, rs33990080. Altogether, among EUR cohort we report 69 carriers out of 214 versus controls 165 out of 896 (MAF: cases 0.18; MAF: controls 0.09) and OR: 1.9 (p-value logistic model 10^−6). The significant effect persists when idiopathic cases are compared with diabetic cases as the MAF of diabetic cases (0.10) is comparable to that of population controls (0.09). Solute carrier family 15 (SLC15) A4 is a lysosome-resident amino acid/oligopeptide transporter that is preferentially expressed in immune cells. It is required for TLR7/9-dependent type I interferon production and plays a critical role in the pathogenesis of lupus and colitis. SLC15A4 was shown to mediate M1-prone metabolic shifts in macrophages and guards immune cells from metabolic stress. Previous reports have shown that when the anti-inflammatory M2 macrophages are switched to pro-inflammatory M1 macrophages, delayed GE was evident in animal models. Current genetic findings suggest that a mechanism directly connected to macrophage polarization may be implicated in a subset of idiopathic gastroparesis patients.
2014-12-20 | Future Directions in the Treatment of Gastroparesis
Understanding of gastroparesis is evolving, in part because of systematic studies on the pathology, pathophysiology, and outcomes. It is clear that simply accelerating gastric emptying may not effectively control symptoms in this syndrome and more creative approaches are required that address aberrant sensation (vagal and spinal) as well as regional disturbances in motility. Further, with the growing recognition of a possible inflammatory basis, the prospects of disease modifying now seem realistic.
2014-07-13 | Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis.
Abstract Background There is increasing evidence for specific cellular changes in the stomach of patients with diabetic ( DG ) and idiopathic ( IG ) gastroparesis. The most significant findings are loss of interstitial cells of Cajal ( ICC ), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD 206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD 206+ and i NOS + cells. To investigate associations between cellular phenotypes and ICC . Methods Full thickness gastric body biopsies were obtained from non‐diabetic controls (C), diabetic controls ( DC ), DG , and IG patients. Sections were labeled for CD 45, CD 206, Kit, i NOS , and putative human macrophage markers ( HAM 56, CD 68, and EMR 1). Immunoreactive cells were quantified from the circular muscle layer. Key Results Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD 206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between i NOS + cells and ICC in the DC group, but not the other groups. CD 68 and HAM 56 reliably labeled the same cell populations, but EMR 1 labeled other cell types. Conclusions & Inferences Depletion of ICC and correlation with changes in CD 206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD 206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages.
2006-05-12 | 13 Role of local progenitors in the sustenance of networks of interstitial cells of Cajal (ICC) in the murine stomach
Depletion of ICC networks and consequent changes in electrical slow wave activity and neuromuscular neurotransmission play important roles in diabetic and idiopathic gastroparesis. We have shown that reduced insulin/IGF‐I signaling and consequent decrease in stem cell factor (SCF) production underlie the ICC depletion of diabetic gastroparesis. It is, however, unclear whether the ICC loss is caused primarily by the accelerated attrition of mature cells or their impaired regeneration. In this study we identified local ICC progenitors and studied their role in the sustenance of gastric ICC networks. We investigated the expression of CD34, a putative marker for ICC precursors, and receptors for SCF (Kit), insulin, and IGF‐I in murine gastric muscles by flow cytometry and immunohistochemistry. In freshly dissected tissues, CD34 was not detected in Kit Bright ICC but a small population of Kit Low cells expressed high levels of CD34. These cells were oval‐shaped, had no processes, and occurred in small clusters on the serosal and submucosal surfaces of the gastric musculature and in the myenteric region. Unlike mature ICC, they expressed insulin and IGF‐I receptors. Kit Low CD34 + cells were undetectable and Kit + ICC were profoundly reduced in gastric muscles cultured in the absence of growth factors for up to 85 days. Soluble SCF added to the culture media for 32–85 days rescued Kit Low CD34 + cells and caused their growth into densely packed clusters in the myenteric region or thick chords containing bipolar cells within the muscle layers. These cells had elevated Kit and reduced CD34 expression. Cultures treated in a similar manner with IGF‐I to stimulate both soluble and membrane‐bound SCF were dominated by normal, Kit + CD34 – ICC networks. IGF‐I treatments were only effective when initiated within the first 2–4 weeks of culturing, although mature, Kit + ICC were able to survive longer. In adult H‐2K b ‐tsA58 mice harbouring the temperature‐sensitive large tumour antigen encoded by a mutant strain of simian virus 40, stimulating cell proliferation by culturing at 33°C prevented the decline of gastric ICC even in the absence of exogenous growth factors. We conclude that maintenance of gastric ICC probably involves their regeneration from rare Kit Low CD34 + precursors that depend on a nearly uninterrupted supply of insulin or IGF‐I. While the development of these cells into ICC can be initiated with soluble SCF, their expansion and conversion into mature, CD34 – ICC also requires membrane‐bound SCF. Supported by NIH Grants DK58185 and RR16464.
cell therapies
2026-06-01 | Achieving Symptom Control in the Treatment of Gastroparesis: From Pills to Pacing
Abstract Background Gastroparesis is a chronic disorder of the stomach characterized by delayed emptying without mechanical obstruction. Affected patients experience nausea, vomiting, and a feeling of fullness. Achieving sufficient symptom control remains challenging. Aims The aim of this retrospective study was to analyse the use and effectiveness of current treatment options employed in a step-up approach: 1.Dietary changes, 2.pharmacological treatment (prokinetic drugs including domperidone and prucalopride, and laxatives), 3.pyloric interventions (endoscopic balloon dilation, gastric per-oral endoscopic myotomy (G-POEM), laparoscopic surgical pyloromyotomy), and 4.gastric electrical stimulation (GES, EnterraTM). Methods All patients treated for gastroparesis at a tertiary hospital by a dedicated team between 01/2025 and 01/2026 were included. Diagnosis was confirmed by gastric emptying scintigraphy. Exclusion criteria were previous upper gastrointestinal tract surgery, concomitant hiatal hernia or gastroesophageal reflux disease (GERD), and intestinal failure. Main outcome was sufficient symptom control at the latest available follow-up defined as improved or contained symptoms without need for treatment escalation. Results Fifty patients were included. Median age was 39 years (IQR 25-57), 66% were female. Reasons for gastroparesis was idiopathic in 80%, diabetes in 8%, and rheumatologic or neurologic disease in 12%. Most frequent symptoms were feeling of fullness (82%) and nausea (74%). Sufficient symptom control following conservative treatment was achieved in 13 patients (26%). Eighteen patients (36%) underwent at least one pyloric intervention [G-POEM (n=5), dilatation (n=10), laparoscopic pyloromyotomy (n=5)], with five patients (10%) achieving sufficient symptom control. Fifteen patients (30%) received a GES device, of which two-thirds (n=10) achieved sufficient symptom control. Twenty patients (40%) had at least two interventions during their treatment course. Conclusion Adequate symptom control often requires escalation beyond conservative treatment. Many patients need multiple interventions, emphasizing the chronic nature of gastroparesis. These findings highlight the importance of an individualized, multimodal treatment approach and the need to further investigate predictors of treatment response.
2025-10-01 | S1112 Efficacy and Safety of Bioelectrical Therapies for Gastrointestinal Motility Disorders: A Systematic Review and Meta-Analysis
Introduction: Gastrointestinal motility disorders, such as gastroparesis, significantly impair quality of life, with limited effective treatments for refractory cases. Bioelectrical therapies, including gastric electrical stimulation (GES) and combined approaches with pyloric procedures, have been studied as promising interventions. This systematic review and meta-analysis evaluates their efficacy and safety in managing symptoms of gastroparesis and related disorders. Methods: We systematically searched databases for studies (randomized controlled trials, cohort studies, and observational studies) on bioelectrical therapies (GES, GES with pyloroplasty, gastric peroral endoscopic myotomy) in patients with gastroparesis or similar motility disorders. Eligible studies (n = 15) included 1,487 patients, with data on age (range 2–84 years), sex (61.8%–89.4% female), and etiologies (diabetic, idiopathic, postsurgical). Primary outcomes were changes in symptom severity (Gastroparesis Cardinal Symptom Index [GCSI] score), with secondary outcomes including gastric emptying time, quality of life (QoL), hospital admissions, and adverse events. Data were pooled using standardized mean differences and risk ratios, with heterogeneity assessed via I² statistics. Results: Bioelectrical therapies, particularly GES, significantly reduced symptom severity (pooled GCSI score reduction: 1.2–2.5 points, 10 studies) across diverse cohorts. Combined GES and pyloric procedures showed comparable or superior outcomes, especially in diabetic and idiopathic gastroparesis. Gastric emptying improved in 60% of studies (4-hour retention decrease: 10%–30%). Quality of life scores (GIQLI) and hospital admission rates also improved, though adverse events (e.g., device migration, infection) occurred in 5%–15% of cases. Heterogeneity was moderate (I² = 45%–60%), reflecting variability in study design, stimulation parameters, and follow-up (6 months–17 years). Conclusion: Bioelectrical therapies, combined with pyloric interventions, demonstrate promising efficacy in symptom control for gastrointestinal motility disorders, with acceptable safety profiles. However, variability in protocols and study designs highlights the need for standardized, randomized trials to optimize treatment strategies and patient selection.
2025-01-11 | [Gastric electrostimulation in refractory gastroparesis: results of a explorative observational study].
High-frequency electrical stimulation therapy (gastric electrical stimulation, GES) is a treatment option for gastroparesis of various genesis. The best indication and prognostic parameters have not yet been conclusively determined.Retrospective analysis of all gastroparesis patients implanted with a GES device between 2011 and 2020. Clinical response was measured before and after implantation using a validated Gastroparesis Cardinal Symptom Index (GCSI) (maximum score: 5, minimum score: 0). Other study endpoints included: subjective symptom course (no improvement, partial improvement, or severe improvement) and change in gastroparesis medication.A GES device was implanted in 42 patients (16 M: 26 F, mean age 45 years). The etiology of gastroparesis was diabetic (n=23), idiopathic (n=10) or postoperative (n=9). Eleven patients (26%) had undergone one or more invasive treatments before. GCSI score of the total group was 3.23 preoperatively. The median follow-up time was 12 months. In the overall group, significant improvement in GCSI score was found 3, 6, 9, and 12 months postoperatively-regardless of indication. In multivariate analysis, disease duration of >30 months was associated with a significantly decreased GCSI score at 12 months (p<0.001). Approximately 40% of patients were able to discontinue or significantly reduce gastroparesis medication. At the end of follow-up, 81% of patients reported partial or major improvement in symptoms. During the follow-up period, three patients (7%) died.Gastric electrical neurostimulation is an effective and safe option for refractory gastroparesis-regardless of the underlying disease.
2024-06-12 | Optimal Parameters for Gastric Electrical Stimulation Therapy for Long-Term Symptom Control in Patients with Gastroparesis
Background: Gastric electrical stimulation (GES) therapy is indicated for the treatment of drug-refractory gastroparesis (GP). However, the long-term effects of GES therapy on GP symptom control and identification of the optimal parameters to activate this long-term efficacy have not been investigated. Methods: We conducted a retrospective cohort analysis of 57 GP patients who received GES and pyloroplasty (PP). The interrogation of the GES system and assessment of GP symptoms were conducted at the initiation of GES therapy and during follow-up visits. We determined the changes in GES parameters including voltage (V), impedance (I), and current (C). The outcome was total symptom score (TSS), which was measured by self-reported GP symptoms. Results: The mean age of patients was 44 (±14) years, and 72% were females. The etiology for GP was diabetes mellitus in 72% and idiopathic in 28%. The median duration of GES follow-up was 47 months (range 5–73) A significant decrease was found in individual symptom scores and the TSS (−10.8; 95%CI: −12.6, −9.08) compared to baseline scores (p < 0.0001). During follow-up, readings for I (515 vs. 598 Ω), V (3.3 vs. 4.8 V), and C (6.5 vs. 8.4 mA) significantly increased (p ≤ 0.0001 for all parameters). Higher GES settings were associated with lower TSS in the adjusted analysis (RC, −1.97; 95%CI: −3.81, −0.12, p = 0.037). Conclusions: these findings suggest that adjusting GES parameters over time based on optimizing symptom improvement should be incorporated into the long-term care of patients receiving gastric neurostimulation therapy.
2023-01-06 | Endoscopic mucosal electrodes: New directions for recording and regulating gastric myoelectric activity
With the gradual deepening of the study of gastric motility disorders, people increasingly realize that gastric myoelectric activity plays an important role in coordinating gastric function. This article introduces the advantages of endoscopic mucosal electrodes compared with traditional electrodes. Several different types of mucosal electrodes and how to fix the electrodes by endoscope are introduced. Endoscopic mucosal electrodes can record and regulate gastric myoelectric activity, which has great value in the study of gastric motility. Endoscopic mucosal electrode technique refers to the fixation of the electrode in the designated part of the gastric mucosa by endoscope. Through endoscopic mucosal electrodes, on the one hand, we can record gastric myoelectric activity, on the other hand, we can carry out gastric electrical stimulation to interfere with gastric rhythm. Endoscopic mucosal electrodes have higher accuracy than traditional cutaneous electrodes, less trauma and lower cost than serosal electrodes. Endoscopic mucosal electrodes have a good application prospect for diseases such as gastroparesis and obesity.
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