Minireviews Open Access
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2019; 25(21): 2581-2590
Published online Jun 7, 2019. doi: 10.3748/wjg.v25.i21.2581
Gastric per-oral endoscopic myotomy: Current status and future directions
Alexander Podboy, Joo Ha Hwang, Linda A Nguyen, Patricia Garcia, Thomas A Zikos, Afrin Kamal, George Triadafilopoulos, John O Clarke, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA 94063, United States
ORCID number: Alexander Podboy (0000-0001-9353-4965); Joo Ha Hwang (000-0002-7534-230X); Linda A Nguyen (0000-0002-3498-6897); Patricia Garcia (0000-0002-9058-9933); Thomas A Zikos (0000-0003-3212-2400); Afrin Kamal (0000-0001-8950-8916); George Triadafilopoulos (0000-0002-4233-3773); John O Clarke (0000-0003-2625-1169).
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: John O Clarke, MD, Associate Professor, Clinical Associate Professor, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 430 Broadway Street, Pavilion C, 3rd Floor, MC: 6341, Redwood City, CA 94063, United States. john.clarke@stanford.edu
Telephone: +1-650-721-6190 Fax: +1-650-724-0533
Received: January 6, 2019
Peer-review started: January 7, 2019
First decision: January 18, 2019
Revised: April 25, 2019
Accepted: April 29, 2019
Article in press: April 29, 2019
Published online: June 7, 2019
Processing time: 153 Days and 1.5 Hours

Abstract

Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis via endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.

Key Words: Gastroparesis, Gastric per-oral endoscopic myotomy, Per-oral endoscopic pyloromyotomy, Myotomy, Endoscopic myotomy, Peroral endoscopic myotomy, Gastric emptying

Core tip: While data regarding the role of per-oral endoscopic pyloromyotomy (G-POEM) for the treatment of gastroparesis are still emerging, it is a promising technique that may significantly benefit specific gastroparesis subtypes with functional gastric outlet obstruction. More data are needed, however, to determine exactly where G-POEM falls in the armamentarium of gastroparesis treatment strategies.



INTRODUCTION

Gastroparesis, characterized by the symptom constellation of early satiety, nausea, vomiting, bloating, postprandial fullness, and upper abdominal pain in the presence of delayed gastric emptying, is an increasingly recognized cause of significant foregut morbidity. Initially thought to be an uncommon disease entity, gastroparesis has experienced a marked increase in prevalence over the past decade; with a growing number of reports indicating increasing emergency room visitations, hospitalizations and health care utilization[1-4].

Gastroparesis is a heterogeneous condition most commonly idiopathic in nature, but also frequently identified in diabetes, connective tissues disease, neurologic disorders, and as a complication of intrathoracic or intrabdominal procedures[5,6]. Numerous underlying pathophysiologic mechanisms have been proposed, but the true pathophysiology of gastroparesis is not well elucidated[5,6]. Because of this limitation, the medical treatment for gastroparesis is largely empiric with the goal of increasing upper gastrointestinal (GI) motility and providing supportive symptomatic relief[5-8]. The only medication that is approved by the Food and Drug Administration for the treatment of gastroparesis at present is metoclopramide; although other agents are frequently used off label. Other medical treatments for gastroparesis includes the use of prokinetic agents such as dopaminergic antagonists like domperidone, utilizing the antibiotic erythromycin’s effects on motilin receptors in the gut to stimulate gastric motility, employment of anti-emetics, or use of neuromodulators[5-9]. Unfortunately, the efficacy of these agents has been limited by the presence of tachyphylaxis, or significant cardiovascular or neurologic side effect profiles that restrict the ability to continue these medical therapies long term[5-9].

In 1986, Mearin et al[10] published a landmark paper that demonstrated abnormally prolonged, high-amplitude pyloric contractions within a subset of patients with gastroparesis. Since that publication, suspected “pylorospasm”, has been the target of a multitude of surgical and endoscopic therapies. These therapies include pyloric injection of botulinum toxin, endoscopic dilatation, placement of trans-pyloric stents, and surgical pyloroplasty or pyloric myotomy[11-18]. However, widespread application of these modalities has been dampened by either the invasiveness of the procedure or a failure to demonstrate consistent long-term efficacy[5,6,11-18]. However, recent advances in endoscopic submucosal dissection have led to the development of novel endoscopic tunneling techniques that have been associated with significant therapeutic potential. Pasricha et al[19] in 2007 incorporated these submucosal tunneling techniques along with an endoscopic myotomy in pigs for treatment of achalasia and subsequently Inoue et al[20] in 2010 first reported the initial clinical experience of these techniques in humans. Since publication of these experiences, these techniques have been increasingly applied to good effect for the treatment of functional esophageal disease[21,22]. Utilizing this successful model as a template, the technical feasibility of per-oral endoscopic pyloromyotomy (G-POEM or POP) was initially described in 2012 by Kawai et al[23] in a porcine model. Following this publication, the first successful G-POEM in humans was described by Khashab et al[24] in 2013. This report details a patient with refractory debilitating gastroparesis who underwent a successful endoscopic pyloromyotomy with marked improvement in symptoms 12 weeks following the procedure[24]. After this initial report, over a dozen published reports of successful G-POEM procedures have been identified in the English literature indicating that we have now entered an era of increased utilization of per-oral endoscopic myotomy for the treatment of gastroparesis[25-34]. The aim of this article is to review the technical aspects of the G-POEM procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.

TECHNICAL ASPECTS OF THE PER-ORAL ENDOSCOPIC PYLOROMYOTOMY PROCEDURE

In our experience, G-POEM for the treatment of gastroparesis is divided into 5 stages: (1) The initial endoscopic inspection; (2) Initial mucosotomy; (3) Submucosal tunnel formation; (4) Pyloric myotomy; and (5) Mucosal Closure (Figure 1).

Figure 1
Figure 1 Per-oral endoscopic pyloromyotomy procedure in 5 steps. A: Initial inspection; B and C: Mucosotomy; D: Submucusal tunnel dissection with identification of pyloric ring; E: Pyloromyotomy; F: Mucosal closure.
Step 1: Initial endoscopic inspection

In stage 1, the initial endoscopic inspection is performed to clear the surgical field of food or residual debris and to identify any contraindications such as mass or ulceration which would preclude continuation of the procedure. At our institution, we commonly assess pyloric distensibility utilizing a 325/8 cm sized endoscopic Functional Lumen Imaging Probe (FLIP, EndoFlip, Medtronic, Sunnyvale, California) during this step (Figure 1A).

Step 2: Mucosotomy

The submucosa is injected with 4-6 mL of lifting solution [0.25% indigo carmine into 500 mL HESPAN (6% Hetastarch in 0.9% Sodium Chloride solution)] 4-5 cm proximal to the pyloric channel along the greater curvature of the stomach. We utilize a triangle tip (TT) endoscopic knife (KD640L, Olympus, Tokyo, Japan) using EndoCut Q setting at 50 W, effect 2 (VIO300D, ERBE, Tϋbingen, Germany) to create a 1-1.5 cm transverse mucosal incision above the submucosal injection (Figure 1B and C).

Step 3: Submucosal tunnel formation

Upon creation of the mucosotomy, the endoscope is advanced into the submucosal space. Submucosal dissection is performed using either the TT or IT-nano (KD 604L or KD 612L, Olympus, Tokyo, Japan) endoscopic knifes, based on anatomic orientation. The submucosal fibers are dissected using spray coagulation mode (50-80 W, effect 2) or forced coagulation mode (50-80 W, effect 2). The submucosal tunnel is extended until the pyloric ring is visualized (Figure 1D). Frequent orientation by exiting the tunnel and visualizing the pylorus is performed throughout creation of the submucosal tunnel to ensure appropriate directionality. Lifting solution is intermittently applied via a spray catheter to aid visualization of the submucosal plane and better demarcate the mucosa and submucosal layers. Any obstructing submucosal vessels are cauterized using coagulation graspers (FD 410 LR, Olympus, Tokyo, Japan) in soft coagulation mode (80 W, effect 3).

Step 4: Myotomy

Upon visualization of the pyloric ring, a full thickness pyloromyotomy down to the serosal layer is performed using either the TT or IT-nano endoscopic knifes with an EndoCut Q current (50 W, effect 2). The myotomy is extended approximately 1-2 cm proximal to the pyloric ring to ensure that the pyloric sphincter has been completely cut (Figure 1D and E).

Step 5: Closure

The mucosal defect is then closed with endoscopic sutures using the OverStitch™ Endoscopic Suturing System (Apollo Endosurgery Inc, Austin, Texas) (Figure 1E). In our practice all patients with medically refractory gastroparesis or with symptom severity sufficient to justify endoscopic intervention are considered for the procedure. Nausea and vomiting are subjectively the symptoms we feel most respond to intervention and we focus on people with these symptoms specifically, rather than those that present primarily with pain. Our practice is to perform a baseline gastric emptying, symptom assessment and assessment of pyloric distensibility (FLIP) prior to (or during) the G-POEM procedure.

Patients are kept nil per os the night before the procedure. If there is a history of gastric food remnant in the stomach, a longer period of a liquid diet is employed to ensure that the stomach is empty for the procedure. Anesthesia is employed to ensure that the patient is kept motionless during the procedure.

Following the procedure, the patient is admitted to the hospital for post procedural observation, initiated on post procedural IV antibiotics and keep on gut rest until a follow up upper GI gastrografin study is obtained the following morning. If no extraluminal contrast is identified the patient’s diet is advanced to a full liquid diet, and the patient is discharged on 5 d of oral antibiotic therapy and acid suppression via twice daily proton pump for 4-8 wk. Our average length of hospitalization is 1-2 d. Repeat gastric emptying, pyloric distensibility and symptom assessment is typically obtained 12 wk post procedure.

CURRENT DATA

Table 1[25-34] depicts the preclinical, procedural and post-procedural outcomes in the largest reported G-POEM or POP reports published to date. When the data are aggregated, a total of 325 patients underwent the G-POEM procedure with 100% noting technical success. Major complications were noted in 8.3% of all patients noted, the most common of which were capnomediastinum or capnoperitoneum followed by antral or prepyloric ulceration and GI bleeding. Only 3 perforations were reported, and all healed with supportive care. The mean length of stay ranged from 1-5 d with a mean procedural length ranging from 37-120 min. Rodriguez et al[29] noted decreased procedural times with increased familiarity with the procedure. The majority of patients were female in their 5th to 6th decade of life and the etiology of gastroparesis was noted to be idiopathic in 45%, diabetic in 28%, and post-surgical in 22%. Other than medical therapy, a wide range of previous treatments for gastroparesis were reported with botulinum toxin and gastric stimulator placement being the two most commonly reported.

Table 1 Depicts pre-clinical demographic and clinical data and post-operative changes to symptoms and gastric emptying.
ArticleShlomovitz et al[25], 2014Gonzalez et al[26], 2017Kahaleh et al[27], 2018Rodriguez et al[28], 2017Rodriguez et al[29], 2018Malik et al[30], 2018Jacques et al[31], 2017Dacha et al[32], 2017Mekaroonkamol et al[33], 2018Khashab et al[34], 2017
n72933471001320163030
Female (%)10065.506678.7085.0053.5881.2586.7057
Age (mean)5152.85243.74545.744.764747
Previous gastric stim4 (13.8%)2 (6%)16 (34.0%)20 (20%)3 (23%)04 (25%)4 (13.3%)0
Previous botox treatment1 (3%)4 (12%)28 (59.6%)46 (46%)11 (84.6%)2 (10%)01 (3%)12 (40%)
Pre GES 4 h (mean %)2140 ± 344537.2 ± 25.139 ± 26.549 ± 245762.563.0 ± 25.537
Pre GCSI3.3 ± 0.94.613.8 ± 0.862.2 ± 0.83.53.413.5 ± 0.6
Gastroparesis: Idiopathic415122756445127
Gastroparesis: Diabetes077122111091211
Gastroparesis: Post-surgical2512819811512
Gastroparesis: Scleroderma0221000
Total of major postoperative complications4/75/291/330/4710/1001/133/200/1612/30
Post GES Residual 4 hours4%28 ± 4517% ± 1720.4 ± 26.116.3 ± 21.433 ± 281525.422.2 ± 20.517% ± 16
Symptom improvement85.70%69%86%73%90%81%76.70%86%
How defined improvementClinical improvementDecrease in GCSIClinical improvement1Not definedNot definedCPGAS scoreGCSI decrease by 0.75Decrease in GCSIDecrease in GCSI2Clinical improvement
Length of follow up (mo)6.5663333126-186
Timing of F/u GES in days8456909084845642-5681-105
GES improvement4/5 (90%)23/29 (79.3%)78% α4/6 (66.7%)19/20 (95%)12/12 (100%)78.3%α14/17, 82.3%
Normalization of GES0/516/294/657% α06/209/1247.8%α8/17

Clinical success was noted in 68%-90% of patients. 3 studies defined clinical success as any symptomatic improvement[25,27,34], with 4 studies identifying any decrease in Gastroparesis Cardinal Symptom Index (GCSI) or Clinical Patient Grading Assessment Scale score as clinical success[26,30,32,33]. Only one study utilized an absolute GCSI decrease (0.75 points) as a marker for success[31]. Two studies did not define parameters for clinical success[28,29]. An improvement in gastric emptying scores at 4 hours was reported in 67%-90% of all patients with follow up Gastric Emptying Study (GES) studies. Normalization of the GES at 4 h was noted in 0-66% of all gastric emptying studies, although significant drop out rates were reported. Eight studies reported follow up intervals of less than 7 mo.

No clinical parameters were identified that reliably predicted G-POEM success. Gonzalez et al[26] noted that female gender and diabetes were associated with a higher rate of failure in a univariant analysis; however, these results were not corroborated in a multivariate analysis. Malik et al[30] and Jacques et al[31] were the only authors to study the pre- and post-pyloric distensibility with FLIP. While Malik et al[30] identified a larger cross sectional area at 40 mL balloon in those that improved with G-POEM, Jacques et al[31] identified that at 50 ml a Distensibility Index of < 9.2 mm2/mmHg was 100% specific and 72.2% sensitive with regards to clinical efficacy of G-POEM. No other parameters were identified that predicted success or failure of the G-POEM procedure. Table 2 depicts the procedural variability across the studies. Note the large variation between studies in regard to the site of mucosotomy, endoscopic equipment used, and post-operative testing and care including antibiotics and acid suppression.

Table 2 Demonstrates procedural data including equipment used and post-operative practice reported across the studies.
ArticleShlomovitz et al[25], 2014Gonzalez et al[26], 2017Kahaleh et al[27], 2018Rodriguez et al[28], 2017Rodriguez et al[29], 2018Malik et al[30], 2018Jacques et al[31], 2017Dacha et al[32], 2017Mekaroonkamol et al[33], 2018Khashab et al[34], 2017
n72933471001320163030
Procedure length (min)90-120147 ± 2277.6 (37-255)41.2 ± 28.533.8 ± 21.6119 ± 2356.549.7 ± 22.148.3 ± 16.572 ± 42
Length of stay (mean)2.35.4 (1-14)1.09 ± 0.61.3 ± 1.052.5 ± 1.4 d3.752.462.4 ± 1.0
Pre ABXYes, IVYes, IVGentamicin washNoneNoneGentamicin washNoneYes, IVYesPost-Op
Site of mucosotomy (cm proximal to pylorus)555-65454-555-75
Mucosal entry locationgreater curvature in 31, 2 patients lesser curvature.Greater curvature 19, anterior wall 9, posterior wall 2greater curvature95 lesser curvature, 4 greater, 1 posteriorgreater curvaturegreater curvaturelesser curvature
Lift Solution5-10 mL 1: 10000 Epi5 mL methylene blue and 500 saline mixturemethylene blue6methylene blueNot usedglycerol5 mL methylene blue and 500 saline mixturesaline and 0.25% indigo carmine solution or methylene blue solution2
Size of mucsoal incision (cm)1-22223-41.5-2
Knife UsedT KnifeTriangle knifeHybrid knife or IT2Triangular knifetriangle tip knifeI-Type Hybrid knifeT-Type for initial incision, Hybrid knife for tunnel, Hook Knife for myotomyHook Knife or I-type knifeI hybrid knifeTriangular tip knife
Size of myotomy mean (cm)23.34 (2-6)3.5 ± 0.83.942-3
Upper GI seriesPOD 1POD 1POD 1-2POD 1POD 1POD 1
Use of PPIBID PPI for 6 wkBID PPI for 4 wkPPI BID for 4 wk w/SucralfateBID PPI and QID sucralfate for at least 2 wkBID for 8 wk
Antibiotics on discharge5 d oral AbxIV Abx following procedure
Dietary restrictionsClear liquid immediately, pureed/soft diet for 2 wk,observed for 1 d NPO, then advanced to clears, observed for 5 d and sent home onClear liquid diet 2-3 d, advanced to gastroparetic dietadvanced to clears with liquid diet for 2 wkliquid diet for 2-4 wkClear liquid diet, advance as toleratedLiquid diet day after procedureadvance to liquid after upper GI and ADATclear liquid and advanced diet over 4 wk courseliquid diet started then advanced to soft then to gastroparetic diet
Total of major post operative complications4/75/291/330/4710/1001/133/200/1612/30
LIMITATIONS

There are several limitations to these published studies. Mainly there is significant heterogeneity between the studies with regards to demographic data, patient selection, pre- and post-operative testing, and in determination and assessment of clinical response. Additionally, the published reports are largely retrospective in nature with no true control groups; moreover, they experienced significant drop out rates in regard to follow up assessment and testing without inclusion of any intention to treat analysis. There was no standard approach towards type or duration of pre-myotomy medications or interventions and no standard approach in determining pre-procedural symptom severity. Furthermore, as highlighted in Table 2, there was no standardized technique with regards to the G-POEM procedure itself, with significant differences in location of myotomy position, myotomy size, equipment used and post-procedural medications and testing.

WHERE DO WE GO FROM HERE?

The above heterogeneity highlights a need for validated formalized pre- and post-operative testing, and careful stratification of symptoms. This would allow objective measurement of gastroparesis severity, which could allow subsequent accurate determination of optimal procedural candidates. Additionally, concurrent or peri-operative use of novel assessments of pyloric pressure and distension via FLIP[35-37], classification of gastric contractile patterns via electrogastrography[38], or response to previous pyloric-directed therapies including pyloric botulinum toxin injection or pyloric stent placement[11-18] could prove useful in identifying a subgroup of patients that would be best served by G-POEM. Moreover, identifying and classifying patients based on emerging histopathologic features of gastroparesis such as loss of intestinal cells of Cajal, degree of collagen fibrosis, smooth muscle abnormalities, or alterations in the gastric muscle macrophage population[39-42] all may prove useful in further stratifying patients into subgroups that may provide further clarity into which patients would best benefit from endoscopic pyloromyotomy.

While the current published literature demonstrates significant optimism regarding the efficacy of G-POEM for the treatment of gastroparesis, gastroparesis itself is a markedly heterogeneous disease entity and caution should be used in interpretation of short term follow-up data in a disease that has demonstrated significant placebo response in the past[43]. Based on this, there is a clear need for a randomized blinded prospective trial, although overall the design of this trial remains unclear. Consideration for G-POEM vs sham procedure is ideal but may have ethical and blinding considerations. Alternative options including randomized crossover studies utilizing G-POEM vs other pyloric-directed therapies, including botulinum toxin injection, pyloric stenting, or surgical pyloromyotomy, is an attractive option that may help mitigate some of the ethical and blinding concerns. Regardless of the approach, these studies are likely best served via multicenter investigation secondary to the total numbers required to power such a study.

Questions including the optimal number of training cases prior to competency also require consideration. Previously published literature in POEM has identified a wide range of conflicting reports for the number of required cases prior to accepted clinical competency, with ranges from 20-100[21-44], and it is not clear if the learning curve for G-POEM follows a similar pattern to POEM. Other potential procedural issues that require future attention include determination/comparison of the various technical aspects of the procedure (i.e., type or location or myotomy) and determination of the optimal timing of G-POEM either sequentially or in combination with other therapeutic modalities for gastroparesis.

Additionally, it is not clear if the ultimate therapeutic efficacy of G-POEM is secondary to pyloric disruption alone or if pyloric disruption results in yet undetermined physiologic alterations. Rao et al[45] previously established that fundic distension via balloon insufflation led to increases in phasic motor activity within the antrum and duodenum. It is unclear whether similar adaptive changes in the fundus or duodenum are seen following endoscopic pyloromyotomy.

CONCLUSION

Gastroparesis is a chronic disease with significant associated morbidity. G-POEM demonstrates an exciting potential therapeutic addition to a limited armamentarium and may ultimately be a safer option than many of the medical options currently available. However, more investigation is needed to identify optimal candidates, including a standardized approach to pre- and post-operative testing, developing a standard endoscopic approach and further studies into the physiologic effects of G-POEM. Ultimately, we suspect that GPOEM may be an excellent candidate for a subgroup of gastroparesis patients with pyloric dysfunction; however, stan-dardization and data are needed to ensure that this procedure is best positioned to help those patients who may most benefit from pyloric intervention.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: United States

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Chiu KW, Mayol J, Triantafillidis JK S-Editor: Yan JP L-Editor: A E-Editor: Ma YJ

References
1.  Wang YR, Fisher RS, Parkman HP. Gastroparesis-related hospitalizations in the United States: Trends, characteristics, and outcomes, 1995-2004. Am J Gastroenterol. 2008;103:313-322.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 221]  [Cited by in F6Publishing: 210]  [Article Influence: 13.1]  [Reference Citation Analysis (0)]
2.  Hirsch W, Nee J, Ballou S, Petersen T, Friedlander D, Lee HN, Cheng V, Lembo A. Emergency Department Burden of Gastroparesis in the United States, 2006 to 2013. J Clin Gastroenterol. 2019;53:109-113.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 35]  [Cited by in F6Publishing: 30]  [Article Influence: 6.0]  [Reference Citation Analysis (0)]
3.  Jung HK, Choung RS, Locke GR, Schleck CD, Zinsmeister AR, Szarka LA, Mullan B, Talley NJ. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009;136:1225-1233.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 375]  [Cited by in F6Publishing: 372]  [Article Influence: 24.8]  [Reference Citation Analysis (0)]
4.  Wadhwa V, Mehta D, Jobanputra Y, Lopez R, Thota PN, Sanaka MR. Healthcare utilization and costs associated with gastroparesis. World J Gastroenterol. 2017;23:4428-4436.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 84]  [Cited by in F6Publishing: 81]  [Article Influence: 11.6]  [Reference Citation Analysis (2)]
5.  Park MI, Camilleri M. Gastroparesis: Clinical update. Am J Gastroenterol. 2006;101:1129-1139.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 95]  [Cited by in F6Publishing: 93]  [Article Influence: 5.2]  [Reference Citation Analysis (0)]
6.  Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L; American College of Gastroenterology. Clinical guideline: Management of gastroparesis. Am J Gastroenterol. 2013;108:18-37; quiz 38.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 824]  [Cited by in F6Publishing: 684]  [Article Influence: 62.2]  [Reference Citation Analysis (0)]
7.  Abell TL, Bernstein RK, Cutts T, Farrugia G, Forster J, Hasler WL, McCallum RW, Olden KW, Parkman HP, Parrish CR, Pasricha PJ, Prather CM, Soffer EE, Twillman R, Vinik AI. Treatment of gastroparesis: A multidisciplinary clinical review. Neurogastroenterol Motil. 2006;18:263-283.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 250]  [Cited by in F6Publishing: 261]  [Article Influence: 14.5]  [Reference Citation Analysis (0)]
8.  Acosta A, Camilleri M. Prokinetics in gastroparesis. Gastroenterol Clin North Am. 2015;44:97-111.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 73]  [Cited by in F6Publishing: 74]  [Article Influence: 8.2]  [Reference Citation Analysis (0)]
9.  Rao AS, Camilleri M. Review article: Metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther. 2010;31:11-19.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 218]  [Cited by in F6Publishing: 192]  [Article Influence: 13.7]  [Reference Citation Analysis (0)]
10.  Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986;90:1919-1925.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 307]  [Cited by in F6Publishing: 270]  [Article Influence: 7.1]  [Reference Citation Analysis (0)]
11.  Arts J, Holvoet L, Caenepeel P, Bisschops R, Sifrim D, Verbeke K, Janssens J, Tack J. Clinical trial: A randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis. Aliment Pharmacol Ther. 2007;26:1251-1258.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 245]  [Cited by in F6Publishing: 217]  [Article Influence: 12.8]  [Reference Citation Analysis (0)]
12.  Friedenberg FK, Palit A, Parkman HP, Hanlon A, Nelson DB. Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol. 2008;103:416-423.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 256]  [Cited by in F6Publishing: 220]  [Article Influence: 13.8]  [Reference Citation Analysis (0)]
13.  Bai Y, Xu MJ, Yang X, Xu C, Gao J, Zou DW, Li ZS. A systematic review on intrapyloric botulinum toxin injection for gastroparesis. Digestion. 2010;81:27-34.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 64]  [Cited by in F6Publishing: 63]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
14.  Clarke JO, Sharaiha RZ, Kord Valeshabad A, Lee LA, Kalloo AN, Khashab MA. Through-the-scope transpyloric stent placement improves symptoms and gastric emptying in patients with gastroparesis. Endoscopy. 2013;45 Suppl 2 UCTN:E189-E190.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 26]  [Cited by in F6Publishing: 29]  [Article Influence: 2.9]  [Reference Citation Analysis (0)]
15.  Khashab MA, Besharati S, Ngamruengphong S, Kumbhari V, El Zein M, Stein EM, Tieu A, Mullin GE, Dhalla S, Nandwani MC, Singh V, Canto MI, Kalloo AN, Clarke JO. Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video). Gastrointest Endosc. 2015;82:1106-1109.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 73]  [Cited by in F6Publishing: 75]  [Article Influence: 8.3]  [Reference Citation Analysis (0)]
16.  Jones MP, Maganti K. A systematic review of surgical therapy for gastroparesis. Am J Gastroenterol. 2003;98:2122-2129.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 154]  [Cited by in F6Publishing: 148]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
17.  Hibbard ML, Dunst CM, Swanström LL. Laparoscopic and endoscopic pyloroplasty for gastroparesis results in sustained symptom improvement. J Gastrointest Surg. 2011;15:1513-1519.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 130]  [Cited by in F6Publishing: 113]  [Article Influence: 8.7]  [Reference Citation Analysis (0)]
18.  Ahuja NK, Clarke JO. Pyloric Therapies for Gastroparesis. Curr Treat Options Gastroenterol. 2017;15:230-240.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 27]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
19.  Pasricha PJ, Hawari R, Ahmed I, Chen J, Cotton PB, Hawes RH, Kalloo AN, Kantsevoy SV, Gostout CJ. Submucosal endoscopic esophageal myotomy: A novel experimental approach for the treatment of achalasia. Endoscopy. 2007;39:761-764.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 361]  [Cited by in F6Publishing: 403]  [Article Influence: 23.7]  [Reference Citation Analysis (0)]
20.  Inoue H, Minami H, Kobayashi Y, Sato Y, Kaga M, Suzuki M, Satodate H, Odaka N, Itoh H, Kudo S. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010;42:265-271.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1168]  [Cited by in F6Publishing: 1129]  [Article Influence: 80.6]  [Reference Citation Analysis (0)]
21.  Inoue H, Shiwaku H, Iwakiri K, Onimaru M, Kobayashi Y, Minami H, Sato H, Kitano S, Iwakiri R, Omura N, Murakami K, Fukami N, Fujimoto K, Tajiri H. Clinical practice guidelines for peroral endoscopic myotomy. Dig Endosc. 2018;30:563-579.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 101]  [Cited by in F6Publishing: 104]  [Article Influence: 17.3]  [Reference Citation Analysis (0)]
22.  Khashab MA, Familiari P, Draganov PV, Aridi HD, Cho JY, Ujiki M, Rio Tinto R, Louis H, Desai PN, Velanovich V, Albéniz E, Haji A, Marks J, Costamagna G, Devière J, Perbtani Y, Hedberg M, Estremera F, Martin Del Campo LA, Yang D, Bukhari M, Brewer O, Sanaei O, Fayad L, Agarwal A, Kumbhari V, Chen YI. Peroral endoscopic myotomy is effective and safe in non-achalasia esophageal motility disorders: An international multicenter study. Endosc Int Open. 2018;6:E1031-E1036.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 59]  [Cited by in F6Publishing: 61]  [Article Influence: 10.2]  [Reference Citation Analysis (0)]
23.  Kawai M, Peretta S, Burckhardt O, Dallemagne B, Marescaux J, Tanigawa N. Endoscopic pyloromyotomy: A new concept of minimally invasive surgery for pyloric stenosis. Endoscopy. 2012;44:169-173.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 73]  [Cited by in F6Publishing: 74]  [Article Influence: 6.2]  [Reference Citation Analysis (0)]
24.  Khashab MA, Stein E, Clarke JO, Saxena P, Kumbhari V, Chander Roland B, Kalloo AN, Stavropoulos S, Pasricha P, Inoue H. Gastric peroral endoscopic myotomy for refractory gastroparesis: First human endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2013;78:764-768.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 192]  [Cited by in F6Publishing: 184]  [Article Influence: 16.7]  [Reference Citation Analysis (0)]
25.  Shlomovitz E, Pescarus R, Cassera MA, Sharata AM, Reavis KM, Dunst CM, Swanström LL. Early human experience with per-oral endoscopic pyloromyotomy (POP). Surg Endosc. 2015;29:543-551.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 113]  [Cited by in F6Publishing: 121]  [Article Influence: 12.1]  [Reference Citation Analysis (0)]
26.  Gonzalez JM, Benezech A, Vitton V, Barthet M. G-POEM with antro-pyloromyotomy for the treatment of refractory gastroparesis: Mid-term follow-up and factors predicting outcome. Aliment Pharmacol Ther. 2017;46:364-370.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 103]  [Cited by in F6Publishing: 77]  [Article Influence: 11.0]  [Reference Citation Analysis (0)]
27.  Kahaleh M, Gonzalez JM, Xu MM, Andalib I, Gaidhane M, Tyberg A, Saumoy M, Baptista Marchena AJ, Barthet M. Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: A multicenter international experience. Endoscopy. 2018;50:1053-1058.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 47]  [Cited by in F6Publishing: 46]  [Article Influence: 7.7]  [Reference Citation Analysis (0)]
28.  Rodriguez JH, Haskins IN, Strong AT, Plescia RL, Allemang MT, Butler RS, Cline MS, El-Hayek K, Ponsky JL, Kroh MD. Per oral endoscopic pyloromyotomy for refractory gastroparesis: Initial results from a single institution. Surg Endosc. 2017;31:5381-5388.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 76]  [Cited by in F6Publishing: 63]  [Article Influence: 9.0]  [Reference Citation Analysis (0)]
29.  Rodriguez J, Strong AT, Haskins IN, Landreneau JP, Allemang MT, El-Hayek K, Villamere J, Tu C, Cline MS, Kroh M, Ponsky JL. Per-oral Pyloromyotomy (POP) for Medically Refractory Gastroparesis: Short Term Results From the First 100 Patients at a High Volume Center. Ann Surg. 2018;268:421-430.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 43]  [Article Influence: 8.6]  [Reference Citation Analysis (0)]
30.  Malik Z, Kataria R, Modayil R, Ehrlich AC, Schey R, Parkman HP, Stavropoulos SN. Gastric Per Oral Endoscopic Myotomy (G-POEM) for the Treatment of Refractory Gastroparesis: Early Experience. Dig Dis Sci. 2018;63:2405-2412.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 79]  [Cited by in F6Publishing: 82]  [Article Influence: 13.7]  [Reference Citation Analysis (0)]
31.  Jacques J, Pagnon L, Hure F, Legros R, Crepin S, Fauchais AL, Palat S, Ducrotté P, Marin B, Fontaine S, Boubaddi NE, Clement MP, Sautereau D, Loustaud-Ratti V, Gourcerol G, Monteil J. Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: Prospective trial with assessment of pyloric function. Endoscopy. 2019;51:40-49.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 74]  [Cited by in F6Publishing: 74]  [Article Influence: 14.8]  [Reference Citation Analysis (0)]
32.  Dacha S, Mekaroonkamol P, Li L, Shahnavaz N, Sakaria S, Keilin S, Willingham F, Christie J, Cai Q. Outcomes and quality-of-life assessment after gastric per-oral endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017;86:282-289.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 92]  [Cited by in F6Publishing: 94]  [Article Influence: 13.4]  [Reference Citation Analysis (0)]
33.  Mekaroonkamol P, Dacha S, Wang L, Li X, Jiang Y, Li L, Li T, Shahnavaz N, Sakaria S, LeVert FE, Keilin S, Willingham F, Christie J, Cai Q. Gastric Peroral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of Life, and Reduces Health Care Use For Patients With Gastroparesis. Clin Gastroenterol Hepatol. 2019;17:82-89.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 52]  [Article Influence: 10.4]  [Reference Citation Analysis (0)]
34.  Khashab MA, Ngamruengphong S, Carr-Locke D, Bapaye A, Benias PC, Serouya S, Dorwat S, Chaves DM, Artifon E, de Moura EG, Kumbhari V, Chavez YH, Bukhari M, Hajiyeva G, Ismail A, Chen YI, Chung H. Gastric per-oral endoscopic myotomy for refractory gastroparesis: Results from the first multicenter study on endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017;85:123-128.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 155]  [Cited by in F6Publishing: 161]  [Article Influence: 23.0]  [Reference Citation Analysis (0)]
35.  Gourcerol G, Tissier F, Melchior C, Touchais JY, Huet E, Prevost G, Leroi AM, Ducrotte P. Impaired fasting pyloric compliance in gastroparesis and the therapeutic response to pyloric dilatation. Aliment Pharmacol Ther. 2015;41:360-367.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 119]  [Cited by in F6Publishing: 113]  [Article Influence: 12.6]  [Reference Citation Analysis (0)]
36.  Malik Z, Sankineni A, Parkman HP. Assessing pyloric sphincter pathophysiology using EndoFLIP in patients with gastroparesis. Neurogastroenterol Motil. 2015;27:524-531.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 98]  [Cited by in F6Publishing: 95]  [Article Influence: 10.6]  [Reference Citation Analysis (0)]
37.  Snape WJ, Lin MS, Agarwal N, Shaw RE. Evaluation of the pylorus with concurrent intraluminal pressure and EndoFLIP in patients with nausea and vomiting. Neurogastroenterol Motil. 2016;28:758-764.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 85]  [Cited by in F6Publishing: 75]  [Article Influence: 9.4]  [Reference Citation Analysis (0)]
38.  Wellington J, Scott B, Kundu S, Stuart P, Koch KL. Effect of endoscopic pyloric therapies for patients with nausea and vomiting and functional obstructive gastroparesis. Auton Neurosci. 2017;202:56-61.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 35]  [Cited by in F6Publishing: 40]  [Article Influence: 5.0]  [Reference Citation Analysis (0)]
39.  Grover M, Bernard CE, Pasricha PJ, Lurken MS, Faussone-Pellegrini MS, Smyrk TC, Parkman HP, Abell TL, Snape WJ, Hasler WL, McCallum RW, Nguyen L, Koch KL, Calles J, Lee L, Tonascia J, Ünalp-Arida A, Hamilton FA, Farrugia G; NIDDK Gastroparesis Clinical Research Consortium (GpCRC). Clinical-histological associations in gastroparesis: Results from the Gastroparesis Clinical Research Consortium. Neurogastroenterol Motil. 2012;24:531-539, e249.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 142]  [Cited by in F6Publishing: 133]  [Article Influence: 11.1]  [Reference Citation Analysis (0)]
40.  Farrugia G. Histologic changes in diabetic gastroparesis. Gastroenterol Clin North Am. 2015;44:31-38.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 40]  [Article Influence: 4.4]  [Reference Citation Analysis (0)]
41.  Cipriani G, Gibbons SJ, Miller KE, Yang DS, Terhaar ML, Eisenman ST, Ördög T, Linden DR, Gajdos GB, Szurszewski JH, Farrugia G. Change in Populations of Macrophages Promotes Development of Delayed Gastric Emptying in Mice. Gastroenterology. 2018;154:2122-2136.e12.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 56]  [Article Influence: 9.3]  [Reference Citation Analysis (0)]
42.  Moraveji S, Bashashati M, Elhanafi S, Sunny J, Sarosiek I, Davis B, Torabi A, McCallum RW. Depleted interstitial cells of Cajal and fibrosis in the pylorus: Novel features of gastroparesis. Neurogastroenterol Motil. 2016;28:1048-1054.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 49]  [Cited by in F6Publishing: 46]  [Article Influence: 5.8]  [Reference Citation Analysis (0)]
43.  Camilleri M, McCallum RW, Tack J, Spence SC, Gottesdiener K, Fiedorek FT. Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study. Gastroenterology. 2017;153:1240-1250.e2.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 117]  [Cited by in F6Publishing: 98]  [Article Influence: 14.0]  [Reference Citation Analysis (0)]
44.  Liu Z, Zhang X, Zhang W, Zhang Y, Chen W, Qin W, Hu J, Cai M, Zhou P, Li Q. Comprehensive Evaluation of the Learning Curve for Peroral Endoscopic Myotomy. Clin Gastroenterol Hepatol. 2018;16:1420-1426.e2.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 50]  [Cited by in F6Publishing: 56]  [Article Influence: 9.3]  [Reference Citation Analysis (0)]
45.  Rao SS, Vemuri S, Harris B, Schulze K. Fundic balloon distension stimulates antral and duodenal motility in man. Dig Dis Sci. 2002;47:1015-1019.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 25]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]