Introduction

Gastroparesis is one of the two most common gastric neuromuscular disorders, the other being functional dyspepsia. Gastroparesis is defined and properly diagnosed using a combination of subjective symptoms and objective measures [1]. First, patients should report symptoms thought to represent a delay in gastric emptying, which include epigastric pain, nausea, vomiting, early satiety, and weight loss [1, 2]. Second, a mechanical obstruction should be ruled out; this is typically performed using upper endoscopy, although a careful upper gastrointestinal series with small bowel follow-through can be sufficient. Third, a delay in gastric emptying should be documented. Although a variety of methods can be used to objectively measure gastric emptying, the 4-h solid-phase scintigraphic emptying scan is considered the most valid [1,2,3,4].

The epidemiology of gastroparesis is not well described since patients are often classified using less specific ICD-10 codes for nausea and vomiting. One carefully performed study reported that the observed prevalence of gastroparesis in Olmsted County, Minnesota, was 37.8 in women and 9.6 in men per 100,000 persons [5]. Using prevalence rates for the most commonly known cause of gastroparesis (diabetes), and data from other epidemiologic studies, it is estimated that approximately 10 million US adults suffer from symptoms of gastroparesis. What is better known, however, is the substantial negative impact that gastroparesis imposes on patients and the healthcare system. Using the well-validated short-form 36 questionnaire (SF-36) to assess quality of life, a recently published study reported that mean SF-36 scores for mental health and social functioning in patients with gastroparesis were analogous to scores for patients with serious chronic medical disorders and depression [6]. Another study found that SF-36 subscale scores were lower in gastroparesis patients compared to the US mean general population norm for every subscale except mental health [7]. The economic impact of gastroparesis is also substantial. A questionnaire study of 228 gastroparesis patients found that gastroparesis symptoms reduced annual income in 28.5% and resulted in disability in 11% [6]. Using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) to evaluate charges in gastroparesis-related hospitalizations over a 10-year period Wang and colleagues reported that in 2004, gastroparesis as either the primary or secondary diagnosis accounted for $3500 million in hospital charges and 911,963 hospital days [8]. These facts highlight the need to identify superior treatment options for patients with gastroparesis in order to improve quality of life and reduce its economic burden.

Pathophysiology

Although gastroparesis is generally thought of as a homogenous disorder characterized by delayed gastric emptying, pathophysiologically, gastroparesis is a heterogeneous disorder characterized by abnormalities in fundic tone, antroduodenal dyscoordination, a weak antral pump, gastric dysrhythmias, and abnormal duodenal feedback [1, 2]. Idiopathic gastroparesis is considered to be present in the largest group of patients in whom an underlying cause cannot be identified. Gastroparesis can also develop for a variety of other reasons; some of the most common causes include long-standing diabetes, connective tissue disorders, prior surgery, mesenteric ischemia, and a variety of inflammatory or neurologic disorders [1, 2, 9, 10]. Up to 50% of type I (insulin-dependent) diabetics and 30% of type 2 (noninsulin-dependent) diabetics have symptoms consistent with gastroparesis [11,12,13,14].

Novel Diagnostics

Gastroparesis has traditionally been diagnosed using a solid-phase gastric emptying scan; the 4-h scan is considered the most valid objective measure [3, 4]. Two new methods to evaluate gastric emptying have recently become commercially available. The first involves the use of a novel breath test involving the algae spirulina labeled with a stable isotope measured with gas isotope ratio mass spectrometry. Advantages to this method include the ability to perform the test directly in the office without the need for specialized equipment. Also, the absence of radiation improves the safety of the test, especially in patients who may be subjected to repeat measurements. Spirulina platensis can be readily labeled with 13C during the growing process. 13CO2 is released from the radiolabeled S. platensis during digestion, and this can be easily measured in breath samples. A recent study compared gastric emptying using 13C-labeled S. platensis to standard scintigraphy in 15 healthy volunteers and 15 patients with dyspepsia [15]. The authors reported that when 9 breath samples were collected over 4 h, gastric emptying measured using radiolabeled S. platensis was just as accurate as scintigraphy. Large, prospective studies in patients with gastroparesis will be required to validate these findings.

The second novel diagnostic test is the wireless motility capsule, which measures intestinal transit, pressure, temperature, and pH. The absence of radiation, plus the ability to measure whole gut transit time, increases the attractiveness of this test for many providers. In a prospective, simultaneous study comparing the wireless motility capsule to standard scintigraphy in 61 patients with gastroparesis, the correlation for the motility capsule and scintigraphy was reasonable at 0.73 at 4 h [16]. The additional information provided (pressure and whole gut transit time) may provide useful information in those patients with other disorders of gastrointestinal neuromuscular dysfunction, including scleroderma or colonic inertia. Further prospective trials are needed in larger populations to confirm these results.

Novel Medications

Dopamine Antagonists: Intranasal Metoclopramide

Metoclopramide is a dopamine D2-receptor antagonist that currently remains the only FDA approved medication for control of gastroparesis symptoms. Metoclopramide relieves symptoms through inhibition of emesis as well as prokinetic effects on gut motility (Table 1) [17]. Severe symptoms of nausea and vomiting could limit a patient’s ability to tolerate oral medications, thereby increasing the practicality of intranasal administration, since intestinal absorption is not needed, despite the presence of vomiting or delayed gastric emptying. A multicenter, open-label study reported metoclopramide nasal spray (10 mg, 20 mg) to be well tolerated and as effective as the oral tablet (10 mg) in diabetic patients (n = 89) with gastroparesis symptoms [18]. Common adverse events in subjects included dysgeusia, headache, and fatigue [19]. A multicenter, randomized, double-blind study (n = 285) showed improvement in total symptom scores of gastroparesis in female patients with diabetes but not in male patients [19]. Diabetic females treated with intranasal metoclopramide (10-mg dose n = 65, 14-mg dose n = 70) had a significant improvement in their gastroparesis symptoms including nausea and upper abdominal pain [19]. Two multicenter trials are currently awaiting results: One is a randomized, double-blind, placebo-controlled study of intranasal metoclopramide in women with symptomatic diabetic gastroparesis (ClinicalTrials.gov, NCT02025725), and the other is a randomized, placebo-controlled study of intranasal metoclopramide in men with symptomatic diabetic gastroparesis (ClinicalTrials.gov, NCT02025751).

Table 1 Novel drug effects
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Ghrelin Receptor Antagonists

TZP-101 and TZP-102 ghrelin, an endogenous peptide produced primarily in the gastric mucosa [20], has prokinetic effects mediated by vagal signaling [21] and stimulates phase III of the gastric migrating motor complex [22] (Table 2). Regulation of ghrelin appears to be impaired in patients with diabetic gastroparesis [23]. Early studies of ghrelin receptor agonists lacked efficacy. TZP-101 did not show clear effects on gastric emptying in gastroparesis patients with gastroparesis [24, 25], whereas studies of TZP-102 were stopped due to lack of efficacy in patients with diabetic gastroparesis [24, 25].

Table 2 Mechanisms of action of novel drugs
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Relamorelin

More recently, relamorelin (RM-131), a synthetic ghrelin agonist with greater potency and plasma stability than native ghrelin [26] and both TZP-101 and TZP-102 [26, 27], has shown promise for the treatment of gastroparesis symptoms. Phase I studies on healthy human subjects (n = 16) showed that relamorelin (30 mcg s.c.) increased gastric motor activity [28]. A randomized, double-blind, placebo-controlled crossover study of type II diabetic women (n = 10) with delayed gastric emptying found that those treated with relamorelin (100 mcg s.c.) had an average decrease in gastric emptying halftime (solids) of 66% compared to placebo [29]. A study of type I diabetic patients with delayed gastric emptying (n = 10) who received relamorelin (100 mcg s.c.) showed a 54.7% improvement in gastric emptying halftime of solids compared to placebo [30]. A double-blind trial (n = 204) of diabetic gastroparesis subjects treated with relamorelin (10 mcg s.c.) twice daily (n = 68) for 28 days showed a mean decrease in gastric emptying of about 23 min and improved vomiting frequency when compared to placebo [31]. Patients who had vomiting as a baseline symptom (n = 30) were shown to have additional improvement in other symptoms including nausea, abdominal pain, bloating, and early satiety compared to placebo [31]. A 12-week randomized double-blind study of diabetic patients with gastroparesis (n = 393) showed a decrease in four-symptom composite scores across all relamorelin treatment groups (10, 30, and 100 mcg) compared to placebo [32]. Minimal adverse reactions were reported with the most common being dizziness, headache, and hyperglycemia [29, 31, 32]. Current ongoing studies include a randomized, double-blind, placebo-controlled study of RM-131 on patients with vomiting symptoms and moderate to severe diabetic gastroparesis (ClinicalTrials.gov, NCT02357420).

5-HT Receptor Antagonists

5-HT3 Receptor Antagonists: Granisetron Patch

Serotonin type 3 (5-HT3) receptor antagonists have been used off-label to control nausea and vomiting in gastroparesis patients for years. 5-HT3 receptor antagonists improve symptoms through inhibition of vagal afferent nerves that project to areas in the brain involved in nausea and vomiting [33]. Granisetron is a 5-HT3 receptor antagonist that is FDA approved for the prevention of chemotherapy-associated nausea and vomiting. Granisetron is now available in a transdermal delivery system, which delivers a sustained, controlled dose over the course of 24 h [34]. A multinational, randomized, double-blind study (n = 691) showed that transdermal granisetron was as effective as an oral dose for the control of nausea and vomiting in patients who had received chemotherapy [35]. One concern with the use of 5-HT3 antagonists is the potential for cardiac electrical dysrhythmias, as electrocardiographic changes and arrhythmias have been observed with use of first generation 5-HT3 antagonists [36]. Transdermal granisetron appears to have a decreased risk of electrical dysrhythmias as a recent phase III study (n = 240) since QTc prolongation was present in only 1.1% of patients receiving transdermal granisetron, whereas QTc prolongation was present in 2.7% of patients receiving oral granisetron [37]. Transdermal delivery is an attractive route in patients with gastroparesis as cutaneous absorption is not dependent on oral intake or gastric emptying. An open-label pilot study of 36 patients with refractory gastroparesis symptoms reported a decrease in symptoms scores of 50% of subjects following 2 weeks of transdermal granisetron [38]. An open-label prescription registry study (n = 51) noted that transdermal granisetron (3.1 mg) was effective in reducing symptom severity scores, especially nausea and vomiting, in 76% of gastroparesis patients with refractory symptoms [39].

5-HT4 Receptor Agonists: Revexepride

5-HT4 receptors are located throughout the gastrointestinal tract. Their activation releases acetylcholine at the myenteric plexus, leading to increased muscular contractions and accelerated transit [40, 41]. Previous synthetic 5-HT4 receptor agonists have unfortunately been associated with adverse cardiovascular events. Cisapride and tegaserod are both nonselective 5-HT4 receptor agonists removed from the market due to reported cardiac side effects [42]. Cisapride was associated with QT prolongation, syncope, and ventricular arrhythmias through the activation of hERG potassium channels [42]. Tegaserod was possibly associated with ischemic cardiovascular events, believed to be due to off-target activation of the 5-HT1 receptor, although a subsequent analysis determined that the reported cardiac events were likely not related to tegaserod use [42, 43].

Revexepride is a newly developed, highly specific, and potent 5-HT4 receptor agonist. A double-blind, randomized, placebo-controlled trial of patients with symptoms suggestive of gastroparesis (n = 80) treated with revexepride (0.02, 0.1, or 0.5 mg oral TID) failed to show differences in gastric emptying or symptom scores in treatment versus placebo control groups after 4 weeks of use [44]. One important limitation of this study was that the mean gastric emptying halftime was reported to be normal in the majority of patients at the beginning of the trial, which may have contributed to the lack of measurable difference between groups. It is unclear whether further studies will be carried out as there are no current clinical trials listed for revexepride.

Dopamine Antagonist: Domperidone

Domperidone is a peripherally acting dopamine D2-receptor antagonist that has been used internationally in the treatment of gastrointestinal symptoms for over 30 years. It is available for use in the USA only through an FDA investigational new drug application in gastroparesis patients who have failed standard therapy. Domperidone is a prokinetic and antiemetic medication that has exhibited efficacy similar to metoclopramide in multiple trials for control of gastroparesis symptoms in diabetic patients [45,46,47,48].

Neurokinin (NK) Receptor Antagonists: Aprepitant

Aprepitant is a NK-1 antagonist that is currently FDA approved for chemotherapy-induced nausea and vomiting. NK-1 receptors mediate the effects of substance P, which is a peptide involved in the induction of vomiting [49, 50]. Studies have shown that antagonists of NK-1 receptors improve both acute and delayed emetic responses to chemotherapy [51, 52]. A case report of a patient with idiopathic gastroparesis and refractory nausea and vomiting showed improvement in symptoms for an extended period of ~16 weeks after 2 months of therapy with aprepitant (40 mg daily) [53]. A multicenter, randomized, double-blind study using aprepitant at 125 mg per day for the relief of nausea in patients with nausea and vomiting of presumed gastric origin is currently awaiting results (ClinicalTrials.gov NCT01149369).

Novel Interventional Treatments

Most interventional treatments for gastroparesis patients are directed at the pylorus. Unfortunately, not all patients have pyloric dysfunction and thus may not respond with pyloric-directed therapies. Recent studies have suggested that the subgroup of patients most likely to improve may include those with impaired gastric emptying in the setting of a normal endoscopy (no mechanical obstruction) but with a normal electrogastrography (EGG) with a rate of 3 Hz, suggesting that dysfunction may lie at the pylorus with antral contractions being grossly normal [54]. The following section will exclude botulinum toxin, which has not been shown to be better than placebo in multiple randomized placebo-controlled trials, and is not recommended by the most current American College of Gastroenterology (ACG) clinical guidelines [1].

Transpyloric Stent Placement

Transpyloric stenting (TPS) (Fig. 1) was initially described in a small case series in 2013, with placement of double-layered fully covered self-expandable metallic stents in 3 relatively young patients. These were deployed endoscopically without fluoroscopy, with the proximal end in the gastric antrum. All three cases had improvement or resolution of refractory symptoms with follow-up as long as 174 days [55].

Fig. 1
figure 1

Picture courtesy of John Clarke M.D.

Transpyloric stent.

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A more recent retrospective case series in 2015 included 30 patients (mean age 42; 20 women) with refractory symptoms of nausea and vomiting. These patients underwent TPS placement (48 procedures with 9 patients undergoing at least 1 repeat stent placement) with stent anchorage using either standard through-the-scope clips (n = 2), over-the-scope clips (n = 18), or endoscopic suturing (n = 24, mean number of 2 sutures per procedure). No fixation device was used in 3 procedures. Clinical success, defined as an improvement in refractory symptoms, was greater in patients with predominant nausea and vomiting, and was noted in 75% of all patients. Response was described as considerable, allowing rapid symptom control and discharge of inpatients with intractable nausea and vomiting, although the degree of improvement was not evaluated with validated questionnaires. Stent migration, during a mean follow-up of 146 days, occurred in 59% of overall procedures: 100% in the no fixation group; 50% in the through-the-scope group; 71% in the over-the-scope group; 48% in the endoscopic suturing group. The authors conclude that TPS is not a permanent solution due to stent migration, but may be considered a salvage treatment for intractable symptoms or help to select patients who may respond to more permanent pylorus-directed therapies such as pyloromyotomy [56].

Laparoscopic Pyloroplasty

The use of pyloroplasty for the treatment of gastroparesis originates from older data describing the surgical treatment of infants with functional gastric outlet obstruction due to hypertrophic pyloric stenosis. The most common surgical procedure is the Heineke–Mikulicz pyloroplasty which is typically done laparoscopically (LP). Evidence to support LP includes an initial retrospective study with 28 patients who underwent LP for refractory gastroparesis (patients with prior gastric surgery or undergoing concurrent anti reflux surgery were excluded) [57]. The authors reported a reduction in prokinetic use by 75%, normalization of gastric emptying studies in 71% of patients, and significant improvements in scores for nausea, vomiting, bloating, and abdominal pain, which persisted at 3 months [57].

A more recent large, single-center, retrospective review included 177 patients who underwent LP, although the majority of patients (n = 160) had another concurrent surgical intervention (including fundoplication for reflux disease, Heller myotomy for achalasia or paraesophageal hernia repair) at the time of LP. Gastroparesis was defined loosely by either an abnormal gastric emptying study, endoscopic visualization of retained food or clinical symptoms suggestive of vagal nerve injury during any previous foregut surgery. Slightly less than half of all patients (49%) were on narcotics preoperatively. The morbidity rate was noted at 6.8% with four reoperations and two confirmed leaks, four wound infections, and seven readmissions within 30 days for abdominal pain, nausea, and/or vomiting. The study reported an 86% improvement in gastric emptying scintigraphy and a significant improvement in symptom severity scores at 1 and 6 months post-op. Approximately 10% of patients underwent subsequent surgical intervention with either gastric stimulator implantation, feeding tube placement, or subtotal gastrectomy. The authors concluded that LP is a safe and effective first-line surgical therapy for refractory gastroparesis [58]. Despite these conclusions, none of the published studies so far have included a sham-controlled arm; they are retrospective in nature, and most do not include validated outcome measures.

Endoscopic Implantable Gastric Electric Stimulator (GES)

The gastric electrical neurostimulator (Enterra Therapy System, Medtronic, Inc) consists of two electrical leads attached to the anterior stomach wall near the greater curvature connected to a subcutaneously placed pulse generator. The gastric stimulator, exempted from formal FDA approval for humanitarian reasons, improves symptoms, particularly nausea and vomiting in patients with diabetic gastroparesis. Symptom improvement is less in patients with idiopathic, post-surgical gastroparesis, and patients on chronic opioids [1]. Complications related to device placement include lead migration, bowel obstruction, perforation, and wound complications. A recent study included 138 patients with a mean follow-up of 520 ± 350 days demonstrated a 75% improvement in average symptom scores with at least 43% of patients showing moderate improvement [59]. Furthermore, although LP combined with gastric stimulator placement has theoretical appeal, controlled randomized studies are lacking [60].

Newer techniques include endoscopic placement of temporary gastric electric stimulators to evaluate for a response before more permanent implantation. A double-masked, randomized, placebo-controlled, crossover trial evaluated the effects of 72 h of temporary gastric stimulation and reported a numerical decrease in daily vomiting scores during stimulation, although the results were not significant [61]. A novel wireless GES device that can be implanted endoscopically (placed using an overtube and attached with endoclips) has been developed in a swine model but this device needs to be carefully studied in humans [62].

Gastrectomy

Gastrectomy has customarily been considered an option for patients with refractory post-surgical gastroparesis. More recently, however, laparoscopic subtotal gastrectomy has been proposed as a first-line surgical treatment for gastroparesis refractory to all other interventions (see Fig. 2) or for palliation. Furthermore, this option can be considered in the treatment algorithm for patients who have no improvement after GES placement, based on a 2013 study that compared outcomes of 103 patients treated either with GES (n = 72) or laparoscopic subtotal (n = 27), total (n = 1), or completion gastrectomy (n = 3). 63% of patients in the GES group reported improvement in overall symptoms compared to 87% in the patients with a primary gastrectomy. Based on median Gastroparesis Cardinal Symptom Index (GCSI) scores [total of 9 individual symptom scores, range 0–45; (GES = 18, LSG = 16, p = 0.12)], symptom improvement was similar between both groups. Furthermore, all patients who failed to respond to GES had 100% symptom improvement with a subsequent gastrectomy [63]. A similar study of 35 patients who underwent laparoscopic total, or near-total, gastrectomy for refractory symptoms, reported that six patients suffered a leak requiring surgical repair; however, nausea and chronic abdominal pain improved in 69 and 70% of patients, respectively, at median follow-up of 6 months [64].

Fig. 2
figure 2

An endoscopic and surgical treatment algorithm for persistent or intractable symptoms despite medical therapy. *Gastric electrical stimulation has been shown to be most effective in patients with diabetic gastroparesis who are not on opioids; Assess response to 72 h endoscopic gastric stimulator placement beforehand if available

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Sleeve gastrectomy has also been described in a few case series as effective in improving gastroparesis symptoms. The initial case series indicated an improvement in symptoms in 4 diabetic gastroparesis patients with resolution of symptoms at 6 months [60, 65]. A small series of nine morbidly obese patients with diabetic GP who received laparoscopic longitudinal sleeve gastrectomy indicated resolution of symptoms and improved gastric emptying [60, 66].

Gastric Per-oral Endoscopic Myotomy or GPOEM (Alternatively Called Per-oral Endoscopic Pyloromyotomy or POP)

Gastric per-oral endoscopic myotomy (GPOEM) for refractory gastroparesis is an extension of POEM, a well-studied treatment option for achalasia. The procedure involves an established sequence of mucosal entry, submucosal tunneling, and then myotomy, followed by mucosal closure. The first reported case involved a 27-year-old woman with refractory diabetic gastroparesis with 12 weeks of improvement after transpyloric stent although gastric emptying remained delayed [67]. A retrospective review of 16 patients with predominant nausea and vomiting who underwent GPOEM reported that 81% of patients had significant improvements in the mean GCSI through 12-month follow-up [68]. A European series reported 12 patients with refractory symptoms with a significant improvement in GCSI scores in 85% of cases after 3 months [69]. A multicenter study (n = 30, 16 of whom had failed previous therapies including botulinum toxin injection, TPS and PEG/J placement) reported an observed clinical response, defined as a reduction in the patients’ self-reported symptoms, in 86% of patients during a mean follow-up of 5.5 months [70]. This procedure shows promising clinical outcomes as a new therapy, although larger sham-controlled studies and further studies to identify which patients may have the greatest benefit are warranted.

Future Therapies

Motilin Receptor Agonist: Camicinal

Motilin is an endogenous peptide that facilitates cholinergic activity in the antrum and initiates phase III contractions of the migrating motor complex [71,72,73]. Previous motilin receptor agonists have unfortunately been ineffective in treating gastroparesis and tachyphylaxis was a common side effect [74]. Conversely, clinical studies of the novel motilin receptor agonist ABT-229 demonstrated an increase in gastric emptying rate in healthy volunteers [75] but failed to improve symptoms in diabetic patients with gastroparesis [76, 77]. Mitemicinal (GM-611), a motilin receptor agonist derivative of the macrolide erythromycin, failed to increase gastric emptying above placebo in diabetic patients with gastroparesis [78].

Camicinal (GSK9262040) is a small, selective motilin receptor agonist that has a reduced incidence of tachyphylaxis [79]. A randomized, double-blind, placebo-controlled study (n = 10) showed single oral 125-mg dose of camicinal decreased gastric emptying halftime by approximately 39 min in type 1 diabetics with gastroparesis when compared to placebo [80]. A randomized, double-blind, parallel-group, placebo-controlled study of type I & II diabetic patients with delayed gastric emptying (n = 79) treated with 125 mg oral camicinal had significantly decreased gastric emptying times without a difference in the magnitude of response after 28 days [81].

Highly Selective 5-HT4 Agonists

As described above, 5-HT4 agonists stimulate gastrointestinal motility through release of acetylcholine at the myenteric plexus [40, 41]. Velusetrag (TD-5108) is a highly selective 5-HT4 agonist [42] that has shown promise for controlling symptoms in patients with gastroparesis. Unlike the nonselective drug cisapride, velusetrag appears to have no effect of the hERG potassium channel [82]. A double-blind, placebo-controlled, parallel-group, randomized trial of healthy subjects (n = 60) demonstrated acceleration of gastric emptying halftime by an average of 25 min after multiple doses (9 days) of velusetrag (seen across treatment arms of 15-, 30-, and 50-mg doses) when compared to placebo [83].

RQ-00000010 is another highly selective 5-HT4 receptor agonist currently under investigation. A double-blind study of healthy subjects who received RQ-00000010 (oral 3-mcg doses or greater) had significantly shortened gastric emptying halftime compared to placebo [84]. Repeated doses of RQ-00000010 were well tolerated without a decrease in effect after 8 days [84]. Other 5-HT4 receptor agonists that initially exhibited potential but are not currently in trials include DA-6650 and YPK10811.

NK-1 Antagonist VLY-686 (Tradipitant)

VLY-686 (tradipitant) is a new NK-1 receptor antagonist that is currently in the clinical stage of development. A multicenter, randomized, double-blind, placebo-controlled proof-of-concept study to assess the efficacy of VLY-686 in relieving symptoms of gastroparesis is currently ongoing (ClinicalTrials.gov/NCT02970968).

Conclusion

Gastroparesis is a chronic and often disabling neuromuscular disorder of the upper gastrointestinal tract that negatively impacts patients’ quality of life. Current management options for gastroparesis are unfortunately limited. Gastroparesis patients and clinicians can be hopeful as there are novel medications including ghrelin and motilin receptor agonists being studied that appear to improve symptoms. In the past, therapy of patients with refractory symptoms was limited to open gastrectomy. Yet, surgical advances including pyloric interventions, gastric stimulators, and laparoscopic subtotal gastrectomy have provided additional options for gastroparesis patients with difficult-to-treat symptoms. Future therapies are eagerly anticipated since a significant need exists in this patient population.