# Efficacy of gastric per-oral endoscopic myotomy remains similar after failure of interventional techniques in refractory gastroparesis

Marion Chartier, Henri Duboc, David Moszkowicz, Marie Dior, Maude Le Gall, Benoit Coffin, Heithem Soliman

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## To cite this version:

Marion Chartier, Henri Duboc, David Moszkowicz, Marie Dior, Maude Le Gall, et al.. Efficacy of gastric per-oral endoscopic myotomy remains similar after failure of interventional techniques in refractory gastroparesis. Clinics and Research in Hepatology and Gastroenterology, 2024, 48 (9), pp.102481. 10.1016/j.clinre.2024.102481. inserm-05337509

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Submitted on 29 Oct 2025

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Original article

# Efficacy of gastric per-oral endoscopic myotomy remains similar after failure of interventional techniques in refractory gastroparesis

Marion Chartier<sup>a</sup>, Henri Duboc<sup>a,b</sup>, David Moszkowicz<sup>b,c</sup>, Marie Dior<sup>a</sup>, Maude Le Gall<sup>b</sup>, Benoit Coffin<sup>a,b</sup>, Heithem Soliman<sup>a,b,*</sup>

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## ARTICLE INFO

**Keywords:**

Gastroparesis

G-POEM

Pyloromyotomy

Gastric electrical stimulation

Gastric emptying

## ABSTRACT

**Background and aims:** Gastric per-oral endoscopic myotomy (G-POEM) is a new therapeutic option for the treatment of refractory gastroparesis. However, the outcome of G-POEM after the failure of gastric electrical stimulation (GES) or other pylorus-targeting therapies has been poorly reported.

**Methods:** Data were collected from patients referred for G-POEM for refractory gastroparesis. The efficacy in patients with previous interventional techniques was compared to patients naïve to instrumental technique. The primary endpoint was the 6-month clinical success rate, defined as at least a 1-point decrease in the Gastroparesis Cardinal Symptom Index (GCSI).

**Results:** Among 48 patients referred for G-POEM, 32 patients had previous instrumental treatments (66%): 15 (31%) had GES, and 17 (35%) had pyloric endoscopic dilation or toxin injection. The technical success rate was 100%. At 6 months, clinical success was achieved in 25/48 patients (52%) and the GCSI decreased from 3.38 (2.94–3.95) to 2.25 (1.11–3.36) (p < 0.001). The 6-month success rate was similar in patients with or without previous instrumental treatment (50.0% vs 56.3%; p = 0.41). The complication rate was also similar in the two groups (6.3% vs 12.5%; p = 0.59), with only one severe adverse event. The only predictive factor for success at 6 months was a higher body mass index (OR = 1.14 [1.01–1.32]; p = 0.05).

**Conclusion:** G-POEM is safe and remains effective after GES or previous pyloric treatment failure, with 50% efficacy at 6 months. The therapeutic strategy in refractory gastroparesis remains to be defined.

## Introduction

Gastroparesis is defined as the delay in gastric emptying of solid food in the absence of mechanical obstruction [1]. Symptoms include nausea, vomiting, gastric fullness, early satiety, bloating, and upper abdominal pain [2]. Severe forms lead to malnutrition, dehydration, and impaired quality of life [3]. The increasing economic burden and the impact of the disease on mortality have made it a growing concern [4,5]. The first-line treatment relies on dietary modifications, associated with antiemetics and prokinetics [6]. However, 40 to 70% of patients are refractory to a well-conducted medical treatment, therefore gastroparesis remains a challenging condition [3,7].

An impairment in antral motility has been shown in gastroparesis and has led to the development of gastric electrical stimulation (GES) [8]. This therapy has shown efficacy on nausea and vomiting symptoms

in 30 to 50% of patients [9]. The role of the pyloric sphincter has also been demonstrated, in the form of “pylorospasm” on manometric evaluation [10,11]. This pyloric dysfunction has been investigated with endoluminal impedance planimetry (EndoFLIP) and correlated with gastroparesis symptoms [12,13]. Consequently, targeting the pylorus has arisen as an interesting strategy. Botulinum toxin, pneumatic dilation of the pylorus, and pyloric stenting have shown encouraging results, but none of them have been effective or correctly assessed in randomized trials [14,15]. Recently, gastric per-oral endoscopic myotomy (G-POEM) has been introduced as a new endoscopic procedure in the management of refractory gastroparesis [16].

Three prospective trials assessed the G-POEM technique, with success rates of 58–60% at 6 months. A randomized controlled trial, including mainly patients with diabetic gastroparesis, confirmed the efficacy of the procedure, with a 71% success rate 6 months after the

<footnote><sup>a</sup> Assistance Publique- Hopitaux de Paris, Service d'Hépato-Gastro-Entérologie, Hôpital Louis Mourier, DMU ESPRIT AP-HP Nord, Colombes F-92700, France</footnote>

<footnote><sup>b</sup> Université Paris Cité, INSERM, Centre de recherche sur l'Inflammation, F-75018 Paris, France</footnote>

<footnote><sup>c</sup> Assistance Publique- Hopitaux de Paris, Service de Chirurgie Générale et Digestive, Hôpital Louis Mourier, DMU ESPRIT AP-HP Nord, Colombes F-92700, France</footnote>

<footnote>* Corresponding author at: Department of Gastroenterology, Hôpital Louis Mourier, 178 rue des Renouillers, Colombes 92700, France.</footnote>

<footnote>E-mail address: heithem.soliman@aphp.fr (H. Soliman).</footnote>
<table><caption>**Table 1**
Demographics and characteristics of the overall population (n=48 patients).</caption><tr><td>Age (years)</td><td>42.5 (35.3 – 60.0)</td></tr><tr><td>Sex ratio (female)</td><td>30 (63%)</td></tr><tr><td>BMI (kg/m²)</td><td>22.3 (19.4 – 25.9)</td></tr><tr><td colspan="2"><strong>Gastroparesis etiology</strong></td></tr><tr><td>• Postsurgical</td><td>19 (40%)</td></tr><tr><td>• Idiopathic</td><td>16 (33%)</td></tr><tr><td>• Diabetes</td><td>9 (19%)</td></tr><tr><td>• Other</td><td>4 (8%)</td></tr><tr><td colspan="2"><strong>Previous treatment</strong></td></tr><tr><td>• Prokinetics only</td><td>16 (33%)</td></tr><tr><td>• Pyloric dilatation</td><td>15 (31%)</td></tr><tr><td>• Pyloric toxin injection</td><td>2 (4%)</td></tr><tr><td>• Gastric electrical stimulation</td><td>15 (31%)</td></tr><tr><td><strong>Baseline GCSI total score</strong></td><td>3.38 (2.94 – 3.95)</td></tr><tr><td colspan="2"><strong>GCSI subscales</strong></td></tr><tr><td>• Nausea/vomiting</td><td>3.33 (2.33 – 4.00)</td></tr><tr><td>• Floating</td><td>3.50 (2.50 – 5.00)</td></tr><tr><td>• Fullness/early satiety</td><td>3.75 (3.00 – 4.50)</td></tr><tr><td colspan="2"><strong>Baseline gastric emptying scintigraphy</strong></td></tr><tr><td>• 4-hours retention ratio (%)</td><td>39.5 (16.0 – 59.0)</td></tr><tr><td>• Half-time gastric emptying (T<sub>1/2</sub>), (minutes)</td><td>185 (112 – 258)</td></tr></table>

BMI: body mass index

GCSI: Gastric Cardinal Symptom Index

Values are presented as median and interquartile ranges, or numbers and percentages.

<table><caption>**Table 2**
Gastric per-oral endoscopic myotomy procedure (n=48).</caption><tr><td>Duration (minutes)</td><td>52 (45 – 66)</td></tr><tr><td>Technical success</td><td>48 (100%)</td></tr><tr><td colspan="2"><strong>Fibrosis</strong></td></tr><tr><td>• No fibrosis (F0)</td><td>28 (58%)</td></tr><tr><td>• Mild fibrosis (F1)</td><td>8 (17%)</td></tr><tr><td>• Severe fibrosis (F2)</td><td>12 (25%)</td></tr><tr><td colspan="2"><strong>Adverse events</strong></td></tr><tr><td>• Infection</td><td>1 (2%)</td></tr><tr><td>• Bleeding</td><td>2 (4%)</td></tr><tr><td>• Infection and bleeding</td><td>1 (2%)</td></tr><tr><td colspan="2"><strong>Adverse events severity</strong></td></tr><tr><td>• Moderate</td><td>3 (6%)</td></tr><tr><td>• Severe</td><td>1 (2%)</td></tr><tr><td>• Fatal</td><td>0 (0)</td></tr><tr><td><strong>Hospitalization duration (days)</strong></td><td>3 (2 – 4)</td></tr></table>

Values are presented as mean ± standard deviation, or numbers and percentages.

<figure><img src="image_4.png" /><figcaption>**Fig. 1.** Evolution of GCSI total score in the overall population after G-POEM (n=48 patients).</figcaption></figure>

GCSI: Gastroparesis Cardinal Symptom Index

*: p < 0.001.

procedure, significantly better than the 22% success rate after the sham procedure [17]. However, few patients previously treated with either GES or pyloric dilation were included in these series.

The aim of this study was to assess the efficacy and safety of G-POEM in a cohort of refractory gastroparesis patients with previous instrumental treatment failure and to compare them to refractory gastroparesis patients naïve to instrumental technique.

## Methods

### *Study design and patients*

We conducted a monocentric study in our tertiary care hospital from a prospectively collected database. All patients referred for G-POEM for refractory gastroparesis between June 2018 and December 2020 were consecutively included. Gastroparesis was confirmed by gastric emptying scintigraphy, with delayed gastric emptying defined as a gastric retention rate of solid food higher than 10% at 4 hours, and/or 60% at 2 hours [18]. Medically refractory patients were defined as patients with persisting symptoms after 6 months of a well-conducted medical treatment including dietary advice, prokinetics, and/or anti-emetic therapies. A Gastroparesis Cardinal Symptom Index (GCSI) of at least 2.0, using the classical calculation defined below, was mandatory before considering G-POEM. Exclusion criteria were the presence of a medical obstruction or previous gastric surgery with resection of the antrum and pylorus. The previous interventional procedures could include endoscopic pyloric dilation, intrapyloric botulinum toxin injection, and/or GES. Endoscopic pyloric dilation was performed using a 20 mm through-the-scope hydraulic balloon as described previously [15]. All participating patients gave their informed consent. This study complies with MR004 national laws in France (Decision no2018-155, 05/03/2018) about research of public interest and conforms to the ethical guidelines of the Declaration of Helsinki.

### *G-POEM procedure and post-procedure care*

G-POEM was performed under general anesthesia with orotracheal intubation and under CO₂ insufflation by one experienced endoscopist (BC). Intravenous antibiotics (amoxicillin – clavulanic acid or a fluoroquinolone if allergic to penicillin) were administrated at the beginning of the procedure. The procedure was performed with a Fujinon® therapeutic gastroscope with a 2.8 mm channel with a distal cap and a triangular tipped electrosurgical knife (Triangle Knife KD-640L, Olympus®, France). A longitudinal antral mucosal incision was made after submucosal injection on the greater curvature 5 cm before the pylorus, and a tunnel was created by submucosal dissection up to the pyloric ring. During submucosal dissection, the intensity of submucosal fibrosis was determined using a semi-quantitative scale, with F0 for no fibrosis interfering with dissection, F1 for mild fibrosis, and F2 for severe fibrosis interfering with dissection, as previously described for endoscopic submucosal dissection [19]. The myotomy was then performed and extended proximally 2 to 4 cm to the antrum, and ultimately the antral incision was closed using hemostatic clips. In patients with GES, the stimulator was deactivated just before the procedure and reactivated the day after.

Liquid and then a soft diet were allowed the day after G-POEM. Patients were discharged the day after re-alimentation with 4 weeks of double-dose proton-pump inhibitor (PPI) treatment.

### *Post G-POEM evaluation and endpoints*

For every patient, demographic data (age, sex, and body mass index), etiology of gastroparesis, and previous treatments were reported. Gastroparesis severity was assessed based on the GCSI score. GCSI includes 9 items measured on a Likert scale from 0 (absent) to 5 (very severe), evaluating symptoms during the previous 15 days [20]. The three subscales (nausea/vomiting, early satiety/postprandial fullness, and bloating) were recorded from 0 to 5, and the GCSI total score was also calculated. All patients had a clinical evaluation at 1, 6, and 12 months
<figure><img src="image_5.png" /><figcaption>Fig. 2. Evolution of GCSI total score and subscales score after G-POEM in patients with previous instrumental techniques (n=32 patients).</figcaption></figure>

A. Evolution of GCSI total score. B. Evolution of nausea/vomiting score

C. Evolution of bloating score D. Evolution of fullness/satiety score

after the G-POEM. This evaluation included GCSI total score, GCSI subscales, and weight evolution. The G-POEM duration, complications, and length of hospital stay were also recorded.

Clinical success was defined as a reduction in GCSI total score of at least 1.0 point. In the absence of clinical response 6 months after G-POEM, the patient could be offered another therapeutic option. Treatments performed after G-POEM and their efficacy were also reported. The primary outcome was the clinical success of G-POEM at 6 months in patients with and without previous instrumental techniques. Secondary outcomes included GCSI improvement at 1 and 12 months, the evolution of each GCSI subscale at 1, 6, and 12 months, and the complication rate.

## Statistical analysis

Statistical analyses were performed using SPSS 26 software (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp). Results are presented as median and interquartile range, or numbers and percentages. A paired samples Wilcoxon test was performed to compare the evolution of continuous data before and after G-POEM, including GCSI scores. For group comparisons, a Mann-Whitney test was used for numerical data. For categorical data, a chi-squared or Fisher's exact test was performed. Logistic regression was employed for the univariate analysis of predictive factors to calculate the odds ratio (OR) and the 95% confidence interval. The p-values < 0.05 were considered statistically significant.

## Results

### Population

A total of 48 patients underwent G-POEM between June 2018 and December 2020. The baseline characteristics of the patients are summarized in Table 1. The median age was 42.5 years old with 30 women

(63%). The median initial GCSI total score was 3.38 (2.94–3.95) with a median 4-hour gastric retention rate for solids of 39.5% (16.0 – 59.0).

Thirty-two patients (66.7%) have previously been treated with instrumental techniques. Fifteen patients had one or several endoscopic pyloric dilatations (31%). This treatment was not effective for 7 patients, it led to an incomplete improvement in 2 patients, and the remaining 6 patients had transient symptom improvement, lasting 10 months on average. Two patients had a previous intrapyloric botulinum toxin injection (4%), one experienced an improvement for 4 months, and the second did not respond to the treatment. Finally, 15 patients had a previous GES implantation (31%), of whom 7 showed no improvement and 8 insufficient improvement.

### Efficacy of G-POEM

Technical success was achieved in 48 patients (100%), with the details of the procedure shown in Table 2. Clinical success at 6 months was achieved in 25/48 patients (52%). The median GCSI score decreased significantly from 3.38 (2.94–3.95) to 2.25 (1.11–3.36) (p < 0.001) at 1 month, and to 2.11 (1.42–3.10) (p < 0.001) at 6 months. The evolution of the GCSI total score is presented in Fig. 1. Follow-up 12 months after G-POEM was available for 45 patients and clinical efficacy was sustained in 18 patients (40%) with a median GCSI of 1.83 (0.58–3.50), which was still significantly lower than at baseline (p < 0.001).

### Efficacy in patients with previous instrumental procedure

The evolution of GCSI total score and subscale scores in the group of 32 patients previously treated with instrumental techniques is presented in Fig. 2. The median GCSI score decreased from 3.38 (3.03–3.95) to 1.97 (1.42–3.70) (p < 0.001) at 6 months, with a success rate of 50% (16/32) and a sustained improvement up to 12 months. A significant improvement was observed for the nausea/vomiting and the fullness/

<footnote>*: p < 0.01; #: p < 0.001; ns: non-significant.</footnote>
<table><caption>**Table 3**
Comparison of patients with or without previous instrumental technique.</caption><thead><tr><th></th><th>Naïve to instrumental treatment (n=16)</th><th>Previous instrumental treatment (n=32)</th><th>p</th></tr></thead><tbody><tr><td>Age (years)</td><td>51.0 (37.2 – 64.5)</td><td>41.6 (32.3 – 59.8)</td><td>0.30</td></tr><tr><td>Sex ratio (female)</td><td>11 (68.8%)</td><td>19 (59.4%)</td><td>0.53</td></tr><tr><td>BMI (kg/m²)</td><td>23.6 (21.4 – 26.1)</td><td>20.8 (19.1 – 25.5)</td><td>0.21</td></tr><tr><td>Gastroparesis etiology</td><td></td><td></td><td></td></tr><tr><td>Postsurgical</td><td>10 (62.5%)</td><td>9 (28.1%)</td><td>0.02</td></tr><tr><td>Idiopathic</td><td>3 (18.8%)</td><td>13 (40.6%)</td><td>0.20</td></tr><tr><td>Diabetes</td><td>3 (18.8%)</td><td>6 (18.8%)</td><td>0.99</td></tr><tr><td>Other</td><td>0 (0%)</td><td>4 (12.5%)</td><td>0.29</td></tr><tr><td>Baseline GCSI</td><td></td><td></td><td></td></tr><tr><td>Total score</td><td>3.36 (2.79 – 4.01)</td><td>3.38 (3.03 – 3.95)</td><td>0.94</td></tr><tr><td>Nausea/ vomiting score</td><td>3.00 (2.33 – 4.33)</td><td>3.33 (2.42 – 4.00)</td><td>0.81</td></tr><tr><td>Bloating score</td><td>3.50 (2.00 – 5.00)</td><td>3.50 (2.50 – 4.88)</td><td>0.93</td></tr><tr><td>Fullness/satiety score</td><td>3.25 (3.00 – 4.50)</td><td>3.75 (2.81 – 4.44)</td><td>0.87</td></tr><tr><td>Gastric scintigraphy</td><td></td><td></td><td></td></tr><tr><td>4 h retention rate (%)</td><td>43.0 (16.0–54.5)</td><td>39.0 (15.5–66.0)</td><td>0.65</td></tr><tr><td>T 1/2 (minutes)</td><td>132 (105–235)</td><td>213 (173–305)</td><td>0.12</td></tr><tr><td>Success rate at 6 months</td><td>9 (56.3%)</td><td>16 (50.0%)</td><td>0.68</td></tr><tr><td>Delta GCSI at 6 months</td><td></td><td></td><td></td></tr><tr><td>Total score</td><td>1.11 (0.81–2.39)</td><td>1.00 (0.33–1.85)</td><td>0.48</td></tr><tr><td>Nausea/ vomiting score</td><td>2.00 (1.58–2.42)</td><td>1.00 (0.33–2.33)</td><td>0.38</td></tr><tr><td>Bloating score</td><td>1.00 (0.75–2.13)</td><td>0.50 (0.00–1.50)</td><td>0.29</td></tr><tr><td>Fullness/satiety score</td><td>1.13 (0.44–2.31)</td><td>1.00 (0.25–2.25)</td><td>0.84</td></tr><tr><td>Complications</td><td>2 (12.5%)</td><td>2 (6.3%)</td><td>0.59</td></tr></tbody></table>

GES: gastric electrical stimulation

BMI: body mass index

GCSI: Gastroparesis Cardinal Symptom Index

T 1/2: half-time rate of gastric emptying

Values are presented as median and interquartile range, or numbers and percentages.

satiety subscales (p < 0.001), but not for the bloating subscale at 6 months. The demographics and baseline characteristics of these patients were compared to those of 16 patients naïve to previous instrumental treatment (Table 3). No significant difference was observed in age, sex, BMI, baseline GCSI or scintigraphy parameters. The only difference was a higher rate of patients with postsurgical gastroparesis in the group of patients naïve to previous instrumental technique (62.5% vs 28.1%; p = 0.02).

Patients with previous GES and those with previous pyloric treatment were compared as shown in Table 4. Patients with previous GES were younger (36.2 vs 52.8 years old; p < 0.05), but there was no difference in the symptomatic scores or scintigraphy parameters. The success rate of G-POEM at 6 months, the GCSI improvement, and the complication rate also did not differ between patients with previous GES or previous pyloric treatment.

### Predictive factors of response to G-POEM

The difference between responders and non-responders to G-POEM treatment is shown in Table 5. In univariate analysis, only a higher body mass index (BMI) was predictive of clinical response to G-POEM at 6 months (OR = 1.14 [1.01–1.32]; p = 0.05), such as the clinical success at 1 month (OR = 3.46 [1.01–13.19]; p = 0.04). A trend for a better response rate was observed in patients with diabetes (OR = 3.89 [0.89–26.4]; p = 0.08). The response rate was 77.8% (7/9 patients) in diabetic gastroparesis, 56.3% (9/16) in idiopathic gastroparesis, and 47.4% (9/19) in postoperative patients, and no success was observed in patients with systemic disease.

<table><caption>**Table 4**
Comparison regarding previous instrumental intervention.</caption><thead><tr><th></th><th>Previous GES treatment (n=15)</th><th>Previous pyloric treatment (n=17)</th><th>p</th></tr></thead><tbody><tr><td>Age (years)</td><td>36.2 (30.4 – 48.3)</td><td>52.8 (37.5 – 66.7)</td><td>&lt;0.05</td></tr><tr><td>Sex ratio (female)</td><td>10 (66.7%)</td><td>9 (52.9%)</td><td>0.43</td></tr><tr><td>BMI (kg/m²)</td><td>19.6 (17.6 – 26.0)</td><td>21.3 (20.4 – 25.4)</td><td>0.19</td></tr><tr><td>Gastroparesis etiology</td><td></td><td></td><td></td></tr><tr><td>Postsurgical</td><td>3 (20.0%)</td><td>6 (35.3%)</td><td>0.44</td></tr><tr><td>Idiopathic</td><td>6 (40.0%)</td><td>7 (41.2%)</td><td>0.95</td></tr><tr><td>Diabetes</td><td>4 (26.7%)</td><td>2 (11.8%)</td><td>0.38</td></tr><tr><td>Other</td><td>2 (13.3%)</td><td>2 (11.8%)</td><td>0.99</td></tr><tr><td>Baseline GCSI</td><td></td><td></td><td></td></tr><tr><td>Total score</td><td>3.42 (3.03 – 3.83)</td><td>3.33 (2.81 – 4.03)</td><td>0.94</td></tr><tr><td>Nausea/vomiting score</td><td>3.67 (2.67 – 4.67)</td><td>3.00 (2.17 – 4.00)</td><td>0.11</td></tr><tr><td>Bloating score</td><td>3.00 (2.00 – 4.00)</td><td>4.00 (2.75 – 5.00)</td><td>0.22</td></tr><tr><td>Fullness/satiety score</td><td>3.75 (3.00 – 4.00)</td><td>4.00 (2.63 – 4.50)</td><td>0.50</td></tr><tr><td>Gastric scintigraphy</td><td></td><td></td><td></td></tr><tr><td>4 h retention rate (%)</td><td>23.8 (13.0 – 84.3)</td><td>40.0 (23.0 – 65.5)</td><td>0.60</td></tr><tr><td>T 1/2 (minutes)</td><td>168 (86 – 258)</td><td>200 (175 – 326)</td><td>0.97</td></tr><tr><td>Success rate at 6 months</td><td>6 (40.0%)</td><td>10 (58.8%)</td><td>0.48</td></tr><tr><td>Delta GCSI at 6 months</td><td></td><td></td><td></td></tr><tr><td>Total score</td><td>0.86 (0.31 – 1.12)</td><td>1.50 (0.32 – 2.13)</td><td>0.28</td></tr><tr><td>Nausea/vomiting score</td><td>1.00 (0.08 – 2.11)</td><td>1.00 (0.33 – 2.33)</td><td>0.97</td></tr><tr><td>Bloating score</td><td>0.88 (0.00 – 1.81)</td><td>1.25 (0.13 – 2.50)</td><td>0.18</td></tr><tr><td>Fullness/satiety score</td><td>0.25 (-1.25 – 1.13)</td><td>1.50 (0.00 – 2.25)</td><td>0.42</td></tr><tr><td>Complications</td><td>2 (13.3%)</td><td>0 (0%)</td><td>0.21</td></tr></tbody></table>

GES: gastric electrical stimulation

BMI: body mass index

GCSI: Gastroparesis Cardinal Symptom Index

T 1/2: half-time rate of gastric emptying

Values are presented as median and interquartile range, or numbers and percentages.

### Treatments after the G-POEM procedure

Treatments performed in the case of failure or relapse after G-POEM are shown in Fig. 3. Eight patients were treated by GES implantation having not had this treatment previously, of whom 4 were improved by GES (50%). Seven patients were refractory to both G-POEM and GES procedures and were treated by surgical Roux-en-Y gastric bypass, with an improvement in 4 patients. Among those patients, 2 patients had first been improved by G-POEM but had a delayed relapse after 12 months. Finally, 4 patients had a second G-POEM, but the efficacy of this second procedure did not last more than 3 months in any of them.

### Safety of G-POEM

Adverse events occurred in 4 patients (8.3%) and are summarized in Table 2. One infectious complication was successfully managed with antibiotics and did not require other treatments. Two out of 3 bleeding complications occurred in patients under curative anticoagulation and 1 required a blood transfusion. Three complications were considered moderate and 1 severe, according to the ASGE classification of adverse events, with a 12-day hospitalization [21]. None of them was fatal. Patients with previous instrumental treatment did not have a higher risk of complication, as shown in Table 3.

### Discussion

The main results of this cohort are: (1) G-POEM has a clinical success rate of 50% at 6 months in patients previously treated with an instrumental technique; (2) the procedure is safe, even in patients with
<table><caption>**Table 5**
Comparison between responders and non-responders to G-POEM at 6 months.</caption><thead><tr><th></th><th>Responders<br>(n=25)</th><th>Non-responders<br>(n=23)</th><th>p-value</th></tr></thead><tbody><tr><td>Age (years)</td><td>40.1 (32.6-64.5)</td><td>44.3 (37.0-60.2)</td><td>0.55</td></tr><tr><td>Sex (female)</td><td>16 (64.0%)</td><td>14 (60.9%)</td><td>0.83</td></tr><tr><td>BMI (kg/m²)</td><td>23.0 (20.6 - 27.5)</td><td>20.3 (17.6 - 24.4)</td><td>0.02</td></tr><tr><td>Etiology</td><td></td><td></td><td></td></tr><tr><td>Postsurgical</td><td>9 (36%)</td><td>10 (43.5%)</td><td>0.60</td></tr><tr><td>Idiopathic</td><td>9 (36%)</td><td>7 (30.4%)</td><td>0.68</td></tr><tr><td>Diabetes</td><td>7 (28%)</td><td>2 (8.7%)</td><td>0.10</td></tr><tr><td>Other</td><td>0 (0%)</td><td>4 (17.4%)</td><td>0.04</td></tr><tr><td>Previous treatments</td><td></td><td></td><td></td></tr><tr><td>Prokinetics only</td><td>9 (36.0%)</td><td>7 (30.4%)</td><td>0.68</td></tr><tr><td>Pyloric dilation</td><td>10 (40.0%)</td><td>5 (21.7%)</td><td>0.17</td></tr><tr><td>Pyloric toxin injection</td><td>0 (0%)</td><td>2 (8.7%)</td><td>0.22</td></tr><tr><td>GES</td><td>6 (24.0%)</td><td>9 (39.1%)</td><td>0.26</td></tr><tr><td>Baseline GCSI</td><td></td><td></td><td></td></tr><tr><td>Total score</td><td>3.42 (2.89 - 3.89)</td><td>3.33 (2.94 - 4.11)</td><td>0.86</td></tr><tr><td>Nausea/vomiting score</td><td>3.00 (2.50 - 4.00)</td><td>3.33 (2.33 - 4.42)</td><td>0.60</td></tr><tr><td>Bloating score</td><td>3.50 (2.00 - 4.25)</td><td>3.75 (2.50 - 5.00)</td><td>0.57</td></tr><tr><td>Fullness/satiety score</td><td>3.75 (2.75 - 4.38)</td><td>3.63 (3.00 - 4.56)</td><td>0.89</td></tr><tr><td>Symptom score</td><td></td><td></td><td></td></tr><tr><td>Nausea</td><td>4.00 (3.00 - 4.00)</td><td>4.00 (3.00 - 5.00)</td><td>0.83</td></tr><tr><td>Vomiting</td><td>3.00 (2.00 - 4.00)</td><td>4.00 (0.75 - 5.00)</td><td>0.40</td></tr><tr><td>Retching</td><td>3.00 (2.50 - 4.00)</td><td>4.00 (2.75 - 5.00)</td><td>0.87</td></tr><tr><td>Bloating</td><td>4.00 (3.00 - 4.00)</td><td>4.00 (3.00 - 5.00)</td><td>0.38</td></tr><tr><td>Belly feels large</td><td>4.00 (1.00 - 4.50)</td><td>3.50 (2.00 - 5.00)</td><td>0.72</td></tr><tr><td>Stomach fullness</td><td>4.00 (3.00 - 5.00)</td><td>4.00 (3.00 - 5.00)</td><td>0.79</td></tr><tr><td>Early satiety</td><td>4.00 (3.00 - 5.00)</td><td>4.00 (3.00 - 5.00)</td><td>0.84</td></tr><tr><td>Loss of appetite</td><td>3.00 (2.00 - 4.00)</td><td>3.50 (0.50 - 5.00)</td><td>0.71</td></tr><tr><td>Not able to finish a meal</td><td>4.00 (3.00 - 5.00)</td><td>4.00 (4.00 - 5.00)</td><td>0.91</td></tr><tr><td>Gastric scintigraphy</td><td></td><td></td><td></td></tr><tr><td>4 h retention rate (%)</td><td>43.0 (18.5 - 66.0)</td><td>29.0 (13.0 - 54.5)</td><td>0.52</td></tr><tr><td>T 1/2 (minutes)</td><td>219 (119 - 342)</td><td>180 (112 - 237)</td><td>0.40</td></tr><tr><td>Fibrosis</td><td></td><td></td><td></td></tr><tr><td>No fibrosis (F0)</td><td>14 (56.0%)</td><td>14 (60.9%)</td><td>0.73</td></tr><tr><td>Mild fibrosis (F1)</td><td>4 (16.0%)</td><td>4 (17.4%)</td><td>0.99</td></tr><tr><td>Severe fibrosis (F2)</td><td>7 (28.0%)</td><td>5 (21.7%)</td><td>0.74</td></tr><tr><td>Success at 1 month</td><td>17 (68.0%)</td><td>9 (39.1%)</td><td>0.04</td></tr></tbody></table>

BMI: body mass index; GES: gastric electrical stimulation

GCSI: Gastric Cardinal Symptom Index; T₁/₂: half-time rate of gastric emptying Values are presented as median and interquartile range, or numbers and percentages.

previous treatments, with few severe complications; (3) the procedure had similar efficacy in these patients and those naïve to a previous instrumental technique.

Variable efficacy rates have been reported after G-POEM. The first retrospective trial from Khashab et al. reported a success rate of 86% with a median follow-up of 6 months [22]. Subsequent studies revealed an efficacy rate of 69 and 71% at 6 months [23,24]. These differences could be explained by a difference in the definition of clinical success, defined as a self-reported improvement by Khashab et al. [22]. Now, most studies define clinical success as a reduction of 1.0 point in GCSI score [25]. Three non-controlled prospective studies used this definition and reported a clinical success of G-POEM of 58–60% at 6 months [26–28]. Our series reports a similar success rate of 52%, using the same definition. Also, the demographic characteristics of our population are similar to these studies, with a mean age close to 50 years old and about two-thirds of female patients [22,24,26].

Interestingly, the first prospective randomized controlled trial published by Martinek et al. [17] showed better results, reaching an efficacy of 71% at 6 months in 21 patients as compared to 22% in the placebo group (p = 0.005). In this study, the success rate was defined as a decrease of at least 50% in the GCSI total score. The etiology of gastroparesis was mainly diabetes (43%), followed by post-surgical and idiopathic gastroparesis (29% for each). Therefore, our study population seems to be more similar to the population of Vosoughi et al., with a majority of patients with postoperative and idiopathic gastroparesis: 41% and 35% respectively in the study by Vosoughi [26], as compared

to 40 and 33% in our series. These differences could partly explain the different success rates, since Martinek et al. revealed a higher efficacy of G-POEM in patients with diabetic gastroparesis, reaching 89% in this subgroup, as compared to 50% in patients with postoperative gastroparesis [17]. In the current series, patients with diabetic gastroparesis also had a better outcome after G-POEM, although this result did not reach significance (response rate of 78% in this subgroup; p = 0.08). However, other studies did not find the etiology of gastroparesis, including diabetes, to be a predictive factor of the outcome of G-POEM [25].

A unique characteristic of our study population is the high rate of patients previously treated by pyloric dilation and/or GES, accounting for two-thirds of the population. In other prospective trials, patients with GES were not referred for G-POEM [17,26,28], and only 5 patients were reported in the study by Gregor et al., with clinical success in all of them [27]. The current series shows different results, with patients having failed GES having a lower success rate of 40% (6/15) after G-POEM. Nevertheless, this result remains interesting in this subgroup of patients with very refractory gastroparesis given the absence of validated alternative treatment approaches. Patients with previous GES had a trend for a higher nausea/vomiting score at baseline in the current series, which might explain the lower efficacy rate in this subgroup, although the difference in rates was not significant. Indeed, Labonde et al. suggested that a higher nausea subscale score was predictive of G-POEM failure [29]. Moreover, the complication rate was no higher in patients with previous GES, as confirmed by a previous series assessing the safety of G-POEM after failure of GES in 22 patients [30]. This previous series showed an overall improvement in GCSI score, but the clinical success rate was not reported [30]. Finally, a recent multicenter study showed that the efficacy of G-POEM was also similar after previous GES failure, reaching 65% in that series, with no additional complications [31].

Few studies have reported the impact of G-POEM after pyloric dilation and no patient was reported to have had this previous treatment in other prospective trials [17,26–28]. To our knowledge, only 1 patient had this previous treatment in the study by Labonde et al. with subsequent clinical success of G-POEM [29]. Data on previous toxin injection are also scarce, but in the study by Gregor et al. patients seemed to have a better outcome, with efficacy in 19 out of 25 patients (76%) [27]. Whether or not these treatments could be predictive factors or screening procedures before G-POEM still needs to be assessed. Indeed, intrapyloric toxin injection was proposed as a screening test in a study by Wadhwa et al. on 119 patients [32]. Improvement following a previous toxin injection was associated with a better outcome after G-POEM, with a significant OR of 7.7 [2.2–26.1] [32]. On the other hand, another series showed that responses to previous pyloric dilation or toxin injection were not markers of response to G-POEM [33]. This series merged 204 surgical and endoscopic procedures and found that only receiving a preoperative toxin injection was likely to improve the postoperative outcome [33].

Few data are available on the therapeutic strategy after failure or relapse after G-POEM. Some case reports show that performing a second G-POEM could be effective [25]. However, the results of the current series do not support these data since 4 patients who underwent a second G-POEM had at best an early relapse of their symptoms. Another study showed that pyloric dilation could be effective after G-POEM, especially if the EndoFLIP results suggest a persisting pyloric dysfunction [34]. Thus, EndoFLIP could be useful to improve the therapeutic strategy after G-POEM failure. Interestingly, the results of GES were not altered after G-POEM, maintaining 50% efficacy among 8 patients. Thus, whether G-POEM or GES should be performed first still warrants further trials, and predictive factors such as gastroparesis etiology or symptomatic profile could be helpful in therapeutic decision-making. Surgery should be considered only in specialized centers after the failure of every other treatment, especially for vomiting symptoms [35].

Our study confirmed the safety of G-POEM, even in patients with several previous treatments, including GES and pyloric dilation. The
<figure><img src="image_6.png" /><figcaption>Fig. 3. Distribution of patient's treatment before and after the G-POEM procedure.</figcaption></figure>

GES: gastric electrical stimulation

G-POEM: gastric per-oral endoscopic myotomy

RYGB: Roux-en-Y gastric by-pass.

complication rate of 8% was similar to the last published series, ranging from 6 to 9% [17,26,27]. The main adverse events were bleeding and infection, as reported in the literature. Although our data showed a longer duration of hospitalization, the monitoring period was shorter for the last patients included in the study. This was related to the growing experience of our center in using this technique, and the longer duration of hospitalization for the first few procedures is consistent with other studies [36].

This study has several limitations. First, although the data were collected prospectively, this study was a monocentric open-label series with no placebo or control procedure. Patients did not have an analysis of pyloric distensibility, as EndoFLIP was still not available in our unit at the beginning of the study. However, the impact of pre-operative EndoFLIP as a predictive parameter of efficacy has not been proven, and this measurement is not yet recommended in the evaluation of gastroparesis [25,26]. Finally, gastric emptying scintigraphy has not been evaluated after G-POEM, while several studies revealed that G-POEM reduced the gastric emptying rate at 4 hours [17,26]. Nevertheless, gastric emptying scintigraphy is rather difficult to access, and symptom improvement is the most relevant criterion, especially for patients. Moreover, several studies have revealed a poor correlation between symptoms and gastric emptying rate [37].

## Conclusion

To conclude, this series confirmed the efficacy of G-POEM after the failure of previous instrumental techniques, reaching 50% at 6 months, in this population for whom no therapeutic alternative exists. The efficacy and safety after GES or previous pyloric balloon dilation was similar to that in patients naïve to instrumental treatments. The best therapeutic strategy in patients with refractory gastroparesis still needs to be assessed in order to determine whether G-POEM should be performed before or after other instrumental techniques.

## Fundings

None.

## CRediT authorship contribution statement

**Marion Chartier:** Writing – original draft, Methodology, Formal analysis, Data curation, Conceptualization. **Henri Duboc:** Writing – review & editing, Validation, Resources. **David Moszkowicz:** Writing – review & editing, Validation. **Marie Dior:** Validation, Resources. **Maude Le Gall:** Validation. **Benoit Coffin:** Writing – review & editing, Validation, Supervision, Resources, Project administration, Methodology, Conceptualization. **Heithem Soliman:** Writing – review & editing, Writing – original draft, Validation, Methodology, Data curation.

## Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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