- Email: [email protected]
Short-term outcomes of double pyloromyotomy versus single pyloromyotomy at peroral endoscopic pyloromyotomy in treatment of gastroparesis (with video)
Journal Pre-proof Short-term outcomes of double pyloromyotomy versus single pyloromyotomy at peroral endoscopic pyloromyotomy in treatment of gastroparesis (with video) Mohamed M. Abdelfatah, MD, MS. Baiwen Li, MD, PhD, Neil Kapil, MD, Alan Noll, MD, Lianyong Li, MD, Ph.D, Hui Luo, MD, Huimin Chen, MD, Ph.D, Liang Xia, MD, Ph.D., Xiangbo Chen, MD, Vailshali Patel, MD, Parit Mekaroonkamol, MD, Julia Massaad, MD, Steven Keilin, MD, Qiang Cai, MD. PHD PII:
S0016-5107(20)30040-7
DOI:
https://doi.org/10.1016/j.gie.2020.01.016
Reference:
YMGE 11932
To appear in:
Gastrointestinal Endoscopy
Received Date: 31 July 2019 Accepted Date: 8 January 2020
Please cite this article as: Abdelfatah MM, Li B, Kapil N, Noll A, Li L, Luo H, Chen H, Xia L, Chen X, Patel V, Mekaroonkamol P, Massaad J, Keilin S, Cai Q, Short-term outcomes of double pyloromyotomy versus single pyloromyotomy at peroral endoscopic pyloromyotomy in treatment of gastroparesis (with video), Gastrointestinal Endoscopy (2020), doi: https://doi.org/10.1016/j.gie.2020.01.016. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020 by the American Society for Gastrointestinal Endoscopy
Short-term outcomes of double pyloromyotomy versus single pyloromyotomy at peroral endoscopic pyloromyotomy in treatment of gastroparesis (with video) Mohamed M. Abdelfatah#, MD, MS. Baiwen Li#, MD, PhD, Neil Kapil, MD, Alan Noll, MD Lianyong Li, MD, Ph.D. Hui Luo, MD, Huimin Chen, MD, Ph.D, Liang Xia, MD, Ph.D., Xiangbo Chen, Patel Vailshali, MD, Parit Mekaroonkamol, MD, Julia Massaad, MD, Steven Keilin, MD, , Qiang Cai, MD. PHD
Emory University School of Medicine, Division of Digestive Diseases, Atlanta, GA
* This study has been selected to as an oral presentation in DDW 2019 in San Diego in the forum of Cutting Edge of ESD and POEM #
Author share first co-authorship
Corresponding author: Qiang Cai, MD, Ph.D. Professor of Medicine Master Clinician Director, Advanced Endoscopy Fellowship Emory University School of Medicine 1365 Clifton Road, B1262 Atlanta, GA 30322 USA Tel: 404-778-2714 Fax: 404-778-2578 Email: [email protected]
1
Short-term outcomes of double pyloromyotomy versus single pyloromyotomy at peroral endoscopic pyloromyotomy in treatment of gastroparesis (with video) Mohamed M. Abdelfatah, MD, 1# MS. Baiwen Li, MD, PhD, 1,2# Neil Kapil, MD1, Alan Noll, MD, 1 Lianyong Li, MD, Ph.D1,3. Hui Luo, MD1,4, Huimin Chen, MD, Ph.D1,5, Liang Xia, MD, Ph.D. 1,6, Xiangbo Chen MD, 7 Vailshali Patel, MD1, Parit Mekaroonkamol, MD1, Julia Massaad, MD1, Steven Keilin, MD1, Qiang Cai, MD. PHD1
1
Emory University School of Medicine, Division of Digestive Diseases, Atlanta, GA
* This study has been selected to as an oral presentation in DDW 2019 in San Diego in the forum of Cutting Edge of ESD and POEM #
Author share first co-authorship
Current Affiliations: 2. Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 3. Department of Gastroenterology, PLA Strategic Support Force Characteristic Medical Center, Beijing, China 4. State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, China 5. Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
1
6. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University. Nanchang, Jiangxi, China 7. Department of Gastroenteorlogy, Fujian Quanzhou Hospital. Quanzhou, Fujian, China.
Corresponding author: Qiang Cai, MD, Ph.D. Professor of Medicine Master Clinician Director, Advanced Endoscopy Fellowship Emory University School of Medicine 1365 Clifton Road, B1262 Atlanta, GA 30322 USA Tel: 404-778-2714 Fax: 404-778-2578 Email: [email protected]
Author contributions •
MMA assisted in the procedures, collected and analyzed the data, performed statistical work, drafted the paper and implemented all revisions the paper;
•
BL assisted QC in initial concept and design, physically presented in some procedures, assisted in collection, analyzing data, drafting paper and revised the paper;
•
NK, AN assisted in collection and analyzing data and revised the paper;
•
PM, VP and SK assisted in the procedures, interpretation of data and critically revising the intellectual content work it for important; participated discussion and final approval of the version to be published. 2
•
LL, HL, HMC, XL XC, JM physically presented in some procedure, assisted in interpretation of data and critically revising the intellectual content work it for important; participated discussion and final approval of the version to be published.
•
QC obtained IRB, performed the procedure, conceptualized and designed the study, critically revised all the intellectual content of the manuscript; and final approval of the version to be published.
All authors approved the final version of the manuscript.
Disclosures: none Words count: 2256
3
Abstract
Background and Aims: Gastroparesis (Gp) is a chronic debilitating disorder rising in prevalence and hospitalizations. Gastric peroral endoscopic pyloromyotomy (POP or GPOEM) is a novel technique in the treatment of refractory Gp. Despite the initial promising results of GPOEM, one-third of patients do not exhibit any clinical response. Furthermore, loss of clinical response was reported in several studies. No response or loss of response after GPOEM may be related to inadequate myotomy. The aim of our study is to examine whether double pyloromyotomy at GPOEM is superior to single pyloromyotomy.
Method: A retrospective case-controlled study of patients who underwent GPOEM for refractory Gp at our tertiary care institution between June 2015 and March 2018 was performed. Because the follow-up time for the single myotomy group was much longer than that of the doublemyotomy group, we matched the length of follow-up for the single myotomy group to that of the double myotomy group. The outcomes were measured by the changes in Gp cardinal symptom index (GCSI) before and 3 to 6 months after the procedure. Adverse events and other procedural and clinical parameters were also compared.
Results: Ninety patients underwent GPOEM (55 single and 35 double pyloromyotomy) Mean age was 47 ±14 years old, mean duration of symptoms was 5.3 ± 4.4 years. Average GCSI was 3.8 before the GPOEM and the average GCSI 6 months after procedure was 1.8 37 out of 55 (67%) patients underwent single pyloromyotomy achieved clinical response compared with 30 out of 35 (86%) patients receiving double pyloromyotomy. There were no
4
significant differences among procedure time, postoperative pain or length of hospital stay between the 2 groups. There was no difference in adverse events in the 2 pyloromyotomy groups. Conclusion: Double pyloromyotomy is a safe and feasible technique during GPOEM. Clinical success was higher in patients undergoing double pyloromyotomy compared with single pyloromyotomy in this nonrandomized, short-term follow-up study. Long-term studies are needed to further confirm our results.
Keywords: Gastroparesis, POP, Pyloromyotomy, Outcomes, GPOEM
Introduction
Gastroparesis (Gp) is a chronic debilitating disorder with rising prevalence and healthcare burden. (1, 2) Peroral endoscopic pyloromyotomy (POP or GPOEM) adopted the principle of peroral endoscopic myotomy (POEM) for the treatment of achalasia to enable pyloromyotomy by endoscopy in submucosal tunnel. Since it was first reported in 2013 (3), subsequent studies on GPOEM have promisingly reported 62% to 90% success rate in short-term outcomes for Gp patients. (4-18). Other studies have demonstrated that GPOEM improves quality of life and reduces health care utilization in patients with Gp. (12)
Despite the initially promising results of GPOEM, studies showed about one-third of patients did not exhibit clinical response to treatment. Furthermore, partial or complete loss of
5
clinical response during follow-up was reported. (8, 14) One study showed 29% of initial responders may lose clinical response at 2 years postprocedure. (15)
A number of studies have been published which looked at different techniques to improve the outcomes of GPOEM. Full thickness pyloromyotomy was adopted in a few centers. It was reported that full-thickness pyloromyotomy resulted in a high short-term success rates of 81% to 90%, respectively. (10, 17) However, full-thickness pyloromyotomy resulted in a higher rate of intraprocedure bleeding and perforation. In a small study, a 15% rate of perforation was reported.(10)
One theory to explain the lack of initial response or the loss of response in initial GPOEM responders is inadequate pyloromyotomy. In our experience, when Gp symptoms recur, a repeat pyloromyotomy can be performed and still yield an effective result despite technical challenges due to submucosal fibrosis. In the current literature, it is routine to perform only one myotomy. We modified the pyloromyotomy technique by performing 2 separate circular pyloromyotomies, named double pyloromyotomy. We hypothesize that performing double pyloromyotomy at GPOEM can improve outcomes of GPOEM and decrease the recurrence rate after initial response.
Materials and Methods
We conducted a retrospective case-controlled study of consecutive patients who underwent GPOEM for refractory Gp at our institution from June 2015 to March 2019. In our
6
institution, the single circular pyloromyotomy was performed from June 2015 until June 2018. We used the double circular pyloromyotomy technique in all GPOEM patients starting from June 2018. The study was approved by our Institutional Review Board initially on July 25, 2015 and was recently reviewed on July 25, 2019, the IRB number was 00089650.
Because the follow-up time for the single pyloromyotomy group is much longer than that of the double-pyloromyotomy group, in order to make the groups comparable, we matched the follow-up time for the single-pyloromyotomy group to that of the double-pyloromyotomy group to detect initial responders at 3 to 6 months after the procedure. Therefore, we analyzed the outcome data in the single-pyloromyotomy group within the similar length of follow-up.
The procedures were performed mainly by an experienced endoscopist (Q.C.), assisted by a junior faculty or an Advanced Endoscopy fellow in the majority of procedures. Patient characteristics and procedural details were collected. Refractory Gp was defined as gastricemptying study (GES)-confirmed Gp with failure for at least 6 months of dietary modifications and a trial of maximally tolerated doses of prokinetic medications after ruling out mechanical obstruction.
Severity of gastric emptying was graded from 1 to 4 according to gastric retention at 2 or 4 hours as follows: grade 1 (mild), 61% to 70% retention at 2 hours or 11% to 20% retention at 4 hours; grade 2 (moderate), 71% to 80% retention at 2 hours or 21% to 35% retention at 4 hours; grade 3 (severe) 81% to 90% retention at 2 hours or 36% to 50% retention at 4 hours; grade 4 (very severe), 91% to 100% retention at 2 hours or >50% retention at 4 hours. (19, 20) Clinical
7
response was defined as: a decrease of at least 1 point in the average total Gastroparesis Cardinal Symptom Index (GCSI) score with more than a 25% decrease in at least 2 subscales of cardinal symptoms (13).
In our unit, all patients were observed for at least 24 hours after the procedure. A clear liquid diet was initiated the day after the procedure, except for patients with persistent postprocedure pain. For those patients with persistent abdominal pain, abdominal imaging studies, such as upper GI barium study or computed tomography were used to rule out perforation. Patients were discharged the next day with instructions for advancing their diet from liquids to a regular diet over a period of 4 weeks after the procedure.
The protocol of GPOEM was described in detail in our prior studies (11-13). The only difference in this study is adding another myotomy in the double-myotomy group. Briefly, the procedure was performed with a gastroscope (GIF-H190; Olympus, Tokyo, Japan) with a transparent distal cap attachment (MH-588; Olympus, Japan) and Hybrid knife I-type (ERBE, Germany) or a hook knife (Olympus, Japan), using only carbon dioxide for insufflation (UCR, Olympus, Japan). Submucosal tunneling was performed along the posterior wall of the greater curvature of the antrum (3-6 o’clock position) using spray coagulation mode 50 W at effect 2 (ERBE) (Figure 1) After identification of the pyloric ring, a selective circular pyloromyotomy was performed at the 6 or 7 o’clock position in the single pyloromyotomy group, whereas in the double-pyloromyotomy group, another selective cut was performed at the 4 or 5 o’clock position (Figure 1) to keep at least 1 centimeter in between the 2 pyloromyotomies. (Video 1)
8
Descriptive statistics of baseline characteristics were calculated for means and standard deviations. Comparative analyses of pre- and post-GPOEM total GCSI and subscale scores were performed using a repeated measures ANOVA and post-hoc paired t-test. A p-value of less than 0.05 was considered statistically significant for all analyses. Data were analyzed using IBM SPSS Version 22.0 statistical software (IBM Corporation, Armonk, NY, USA)
Results
A total of 90 patients who underwent GPOEM were included in the study; 17 males and 73 females. Mean age was 47 ±14 years old, mean duration of symptoms was 5.3 ± 4.4 years. Average GCSI was 3.8 before the GPOEM (Table. 1). Overall, 67 (74%) patients had adequate clinical response at 3 to 6 months follow-up with the average GCSI improved from 3.8 ± 0.8 to 1.8± 1.4 after GPOEM.
Fifty-five patients had a single pyloromyotomy (40 patients of the single myotomy were previously published mainly comparing the outcome of diabetic and nondiabetic gastroparesis after GPOEM) (11) and 35 had a double pyloromyotomy. There was no difference in patients’ baseline characteristics, severity of delayed gastric emptying, or risk factors (Table 1). There was a significantly higher rate of clinical response in patients who underwent double pyloromyotomy (86%, n= 30/35), compared with (67%, 37 out of 55) those in the singlepyloromyotomy group (p=0.04). (Table 2)
9
In terms of symptomatic improvement, GCSI score improved to 2.1 ± 1.6 in the single pyloromyotomy versus 1.7 ± 1 in the double pyloromyotomy group. There were no significant differences in procedure time between the single-pyloromyotomy and the doublepylorormyotomy group (50.1± 13 versus 49.6 ± 12 minutes). Likewise, there was no difference in length of hospital stay between the 2 groups 1.3 ± 0.7 versus 1.4 ± 0.6 (Table 2, Figure 3). Notably, 2 patients in the single-pyloromyotomy group with initial response who later had recurrent symptoms underwent upper endoscopy revealing a decrease in the diameter of the pylorus opening. Repeat GPOEM showed fibrosis at the myotomy site. The fibrosis may have resulted in stricture of the pyloric ring. Repeat pyloromyotomy resulted in regaining the response in the 2 patients. As shown in Figure 1, the precondition for single or double myotomy is that the pyloric ring is exposed nicely. Based on our experience in the study, double myotomy can be performed in almost all cases without difficulties. Double pyloromyotomy was planned but not performed in only 2 patients who had significant abdominal distention that resulted in difficulty in ventilating the patients, and the anesthesiologist asked us to consider terminating the procedure. In a normal situation, we could suction out air in the stomach lumen and wait for a few minutes for the CO2 to be reabsorbed, then continue the procedure. However, under the study situation, for patients’ safety reasons, we aborted the plan for a second myotomy after a first myotomy had been performed already
There were no reported major adverse events in the double-pyloromyotomy group, compared with 2 in the single-pyloromyotomy group (one incident of tension capnoperitoneum and another of a later bleeding secondary to a mucosotomy site ulcer). The patient with the
10
tension capnoperitoneum was managed by needle decompression and recovered without any consequences, the patient with the bleeding ulcer was managed by endoscopic treatment and oral proton pump inhibitor.
Outcome after consideration of learning curve
One of the major confounders of our results is the potential improvement of our technique and experience with time. However, there is no existing study on the learning curve for GPOEM. We divided the 55 cases with single myotomy into 2 subgroups, the first 27 cases and the later 28 cases and performed a subanalysis to exclude the potential learning effect on the outcome. The clinical response rate for the 2 subgroups were 70% and 64%, respectively, and there were no statistical differences between the 2 (P=0.9). Discussion
Our results suggest a superior short-term (3-6 months) clinical response rate in the patients who underwent double pyloromyotomy compared with single pyloromyotomy. To our knowledge, this is the first study describing the double pyloromyotomy technique and the promising short-term outcome. Furthermore, there were no differences in procedural time, adverse event rates or hospital stay between the 2 groups
The prior literatures indicate that the physiopathology of Gp includes 2 major components. First, an alteration of the gastric motility causes atony of the stomach body, leading to delayed gastric emptying. The second pathophysiologic mechanism underlying Gp is an
11
increase in pyloric tone, which is demonstrated in previous work by Mearin et al. (21) Thus, surgical pyloroplasty and transpyloric stent placement have been shown to be beneficial in early studies. (22,23) All of these results suggest that pyloric spasm has an important role in gastroparetic symptoms. Furthermore, our prior investigation found that when gastroparesis symptoms recur, a repeat pyloromyotomy can be performed and still yield an effective result despite technical challenges due to submucosal fibrosis (11)
There are 2 aspects to improve the outcome of GPOEM. One is to select the appropriate patients who likely will respond to the therapy. There is limited information on the criteria for selecting patients for GPOEM treatment. We tried to divide the patients with Gp into proximal and distal Gp patients by analyzing the image pattern of the gastric emptying study and thereby to facilitate selection of patients before the procedure. The clinical outcome for the first 40 patients showed GPOEM was effective for both diabetic and nondiabetic Gp. (11) Disease duration may affect the outcome of GPOEM: the longer the duration of the disease, the worse the outcome.
The other aspect is to improve the procedural technique by mainly performing an adequate myotomy. In all published studies, it is routine to perform a single myotomy at GPOEM. One of the underlying etiologies of Gp may be the initial immune insult that leads to universal fibrosis and physiologic changes in the GI tract. (11,24) Patients with Gp may have a higher diffuse collagen fibrosis particularly in the pylorus that leads to fibrosis of the pyloromyotomy site in the pyloric muscle. (16, 21) Our results could be explained by the precise disruption of the pyloric ring in 2 locations, resulting in a more effective disruption of the pyloric
12
ring (Figure 3), therefore eliminating or reducing the risk of future fibrotic bridging, stricture or pylorospasm at the pyloromyotomy site. Also, technically, it is safe and feasible to perform double myotomy at GPOEM.
One of the main strengths of our study is the relatively large sample size given the novelty of the procedure. The study design compares all patients in 2 different periods of time, thus eliminating selection bias. Nevertheless, our study has limitations. The retrospective nature of a single center comparing baseline patient characteristics between the 2 groups is subject to confounder bias. One of the most important confounder could be from increased experience over time. We performed subanalysis excluding the potential learning effect on outcome. There was no significant difference between the outcome of our first 27 cases and later 28 cases in the single myotomy group. Our prior study indicated that the learning cases for POEM should be about 20 cases (25). However, at the present time, there are no data on the learning curve for GPOEM. The result did not show any effect of learning curve on the outcome. It could be that the endoscopist (QC) is very experienced in performing POEM, he had already performed at least a hundred POEM procedures before starting GPOEM. However, the retrospective nature of a single center, nonrandomized study comparing baseline patient characteristics between the 2 groups is still subject to confounder bias. The results were suggestive of superiority of the double myotomy only in the short term. It would be interesting to follow these patients and report the recurrence risk in single versus double myotomy in the long term.
In conclusion, double pyloromyotomy during GPOEM is a safe and feasible treatment of Gp with similar procedural time and adverse event rate to that of conventional single
13
pyloromyotomy. However, double pyloromyotomy showed a higher clinical response rate compared with single pyloromyotomy in a 3- to 6-month follow-up period. A larger prospective, randomized study on long-term outcomes is warranted to help refine the technique of this procedure. References 1. Wang YR, Fisher RS, Parkman HP. Gastroparesis-related hospitalizations in the United States: trends, characteristics, and outcomes, 1995–2004. The American journal of gastroenterology. 2008;103:313-22. 2. Jung HK, Choung RS, Locke GR, 3rd, Schleck CD, Zinsmeister AR, Szarka LA, et al. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009;136:1225-33. 3. Khashab MA, Stein E, Clarke JO, Saxena P, Kumbhari V, Roland BC, et al. Gastric peroral endoscopic myotomy for refractory gastroparesis: first human endoscopic pyloromyotomy (with video). Gastrointestinal endoscopy. 2013;5:764-8. 4. Khashab MA, Ngamruengphong S, Carr-Locke D, Bapaye A, Benias PC, Serouya S, et al. Gastric per-oral endoscopic myotomy for refractory gastroparesis: results from the first multicenter study on endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017;85:123-8. 5. Chen H, Cai Q. Gastroparesis: Current Opinions and New Endoscopic Therapies. Gastrointest Endosc Clin N Am. 2019;29:xv-xvi. 6. Chaves DM, de Moura EG, Mestieri LH, Artifon EL, Sakai P. Endoscopic pyloromyotomy via a gastric submucosal tunnel dissection for the treatment of gastroparesis after surgical vagal lesion. Gastrointest Endosc. 2014;80:164. 7. Chung H, Dallemagne B, Perretta S, Lee SK, Shin SK, Park JC, et al. Endoscopic pyloromyotomy for postesophagectomy gastric outlet obstruction. Endoscopy. 2014;46 Suppl 1 UCTN:E345-6. 8. 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;44:169-73. 9. Kahaleh M, Gonzalez JM, Xu MM, Andalib I, Gaidhane M, Tyberg A, et al. Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: a multicenter international experience. Endoscopy. 2018;50:1053-8. 10. Rodriguez JH, Haskins IN, Strong AT, Plescia RL, Allemang MT, Butler RS, et al. Per oral endoscopic pyloromyotomy for refractory gastroparesis: initial results from a single institution. Surg Endosc. 2017;31:5381-8. 11. Mekaroonkamol P, Patel V, Shah R, Li B, Luo H, Shen S, et al. Association between duration or etiology of gastroparesis and clinical response after gastric per-oral endoscopic pyloromyotomy. Gastrointest Endosc. 2019.
14
12. Mekaroonkamol P, Dacha S, Wang L, Li X, Jiang Y, Li L, et al. Gastric Peroral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of Life, and Reduces Health Care Use For Patients With Gastroparesis. Clin Gastroenterol Hepatol. 2019;17:82-9. 13. Dacha S, Mekaroonkamol P, Li L, Shahnavaz N, Sakaria S, Keilin S, et al. Outcomes and quality-of-life assessment after gastric per-oral endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017;86:282-9. 14. 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;46:364-70. 15. Mohamed M. Abdelfatah PM, Neil Kapil, Alan Noll, Huimin Chen Hui Luo, Nikrad Shahnavaz, Steven Keilin, Field Willingham, Jennifer Christie, Qiang Cai. Long term outcome of Gastric Per Oral Endoscopic Pyloromyotomy in treatment of Gastroparesis: A single center experience [abstract]. Gastrointest Endosc 2019;89:AB102. 16. Mekaroonkamol P, Shah R, Cai Q. Outcomes of per oral endoscopic pyloromyotomy in gastroparesiss worldwide. World J Gastroenterol. 2019;25:909-922 17. Jacques J, Pagnon L, Hure F, Legros R, Crepin S, Fauchais AL, et al. Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: prospective trial with assessment of pyloric function. Endoscopy. 2019;51:40-9. 18. Xu J, Chen T, Elkholy S, Xu M, Zhong Y, Zhang Y, et al. Gastric Peroral Endoscopic Myotomy (G-POEM) as a Treatment for Refractory Gastroparesis: Long-Term Outcomes. Can J Gastroenterol Hepatol. 2018;2018:6409698. 19. Rao SS, Camilleri M, Hasler WL, Maurer AH, Parkman HP, Saad R, et al. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterol Motil. 2011;23:8-23. 20. Moraveji S, Bashashati M, Elhanafi S, Sunny J, Sarosiek I, Davis B, et al. Depleted interstitial cells of Cajal and fibrosis in the pylorus: Novel features of gastroparesis. Neurogastroenterol Motil. 2016;28:1048-54. 21. Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986;90:1919-25. 22. Hibbard ML, Dunst CM, Swanstrom LL. Laparoscopic and endoscopic pyloroplasty for gastroparesis results in sustained symptom improvement. J Gastrointest Surg. 2011;15(9):15139. 23. Khashab MA, Besharati S, Ngamruengphong S, Kumbhari V, El Zein M, Stein EM, et al. Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video). Gastrointest Endosc. 2015;82:1106-9. 24. Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, Smyrk TC, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140:1575-85 e8. 25. Dacha S, Mekaroonkamol P, Wang L, Li XY, Jiang YP, Phillips, G, Keilin, S, Willingham, FF, Cai, Q. Outcome and quality of lefe assessment after per oral endosocpic myotomy (POEM) performed in the endosocooy unit with trainees. Srugical Endoscopy. 2018;32:3046-54
15
Table 1. Perioperative baseline characteristics. Single
Double
P value
pyloromyotomy
pyloromyotomy
N= 55
N= 35
Age, mean (SD)
47.9 ±13
47.2 ±14
0.85
Female sex n (%)
46
27
0.46
Post- GPOEM Body mass index (kg/m2)
27 ± 7.7
28 ± 11
0.8
Duration of gastroparesis (Y)
6.3 ± 4.9
4.9 ± 3.9
0.20
Diabetes mellitus
21
17
0.14
Idiopathic
27
18
Postsurgical
7
0
Pre-GPOEM GCSI score (SD)
3.9 ± 0.9
3.7 ± 0.7
0.53
Pre-GPOEM GCSI score nausea vomiting
4.1 ± 1.2
4.3 ± 0.9
0.47
Pre-GPOEM GCSI score early satiety
3.6 ± 1.4
3.5 ± 1
0.78
Pre-GPOEM GCSI score bloating
3.7 ± 1.5
3.2 ± 1.3
0.1
Etiology
GES grades Grade 1
0.4 14%
7%
16
Grade 2
34%
17%
Grade 3
26%
37%
Grade 4
26%
29%
Tube feeding pre GPOEM
7
4
0.2
Gastric stimulator
8
3
0.2
History of chronic pain
29
15
0.06
Non-narcotic pain medication
7
5
0.4
Psychiatric history
34 (61)
12 (34)
0.02
Abbreviations SD: standard deviation, N: Number P values <.05 are bolded as statistically significant. GE, gastric emptying; GCSI, gastroparesis cardinal symptom index
17
Table 2: Study clinical outcomes Single
Double
P value
pyloromyotomy
pyloromyotomy
N= 55
N= 35
Adverse events
2
0
Number of clips used mean
4.3 ± 0.8
4.8 ± 7
0.56
Procedure time, mins (SD)
50.1± 13
49.6 ± 12
0.40
1.3 ± 0.7
1.4 ± 0.6
0.55
Post- GPOEM Body mass index
27.7 ± 11
27.6 ± 7.7
0.9
Post-POP GCSI score (SD)
2.1 ± 1.6
1.7 ± 1.1
0.10
Clinical Success at 3-6 months follow-up
37 (67%)
30 (86%)
0.04*
Recurrence 1-6 months
4 (7%)
1 (2.9%)
0.3
Procedural Factors
In-hospital outcomes Length of stay, days (SD) Treatment outcomes
Abbreviations SD: standard deviation, N: Number P values <.05 are bolded as statistically significant. gastric emptying; GCSI, gastroparesis cardinal symptom index; NV, nausea and vomiting.
18
Figure Legends: Figure 1. Pyloromyotomy sites. Pyloric ring with yellow arrow pointing at the pyloromyotomy site at 3 and 6 o’clock. Figure 2. Outcomes of single and double myotomy at GPOEM. A, Average GCSI changes after single and double myotomy. B, Clinical success after single and double myotomy Figure 3. Endosocpic views of double and single pyloromyotomy. A, Single pyloromyotomy at 6 o’clock. B, Endoscopic view after the first myotomy. C, Double myotomy at 3 and 6 o’clock. D, Endoscopic view after the double myotomy.
19
Gp: gastroparesis, GPOEM; gastric peroral endoscopic pyloromyotomy,
1
S0016-5107(20)30040-7
DOI:
https://doi.org/10.1016/j.gie.2020.01.016
Reference:
YMGE 11932
To appear in:
Gastrointestinal Endoscopy
Received Date: 31 July 2019 Accepted Date: 8 January 2020
Please cite this article as: Abdelfatah MM, Li B, Kapil N, Noll A, Li L, Luo H, Chen H, Xia L, Chen X, Patel V, Mekaroonkamol P, Massaad J, Keilin S, Cai Q, Short-term outcomes of double pyloromyotomy versus single pyloromyotomy at peroral endoscopic pyloromyotomy in treatment of gastroparesis (with video), Gastrointestinal Endoscopy (2020), doi: https://doi.org/10.1016/j.gie.2020.01.016. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020 by the American Society for Gastrointestinal Endoscopy
Short-term outcomes of double pyloromyotomy versus single pyloromyotomy at peroral endoscopic pyloromyotomy in treatment of gastroparesis (with video) Mohamed M. Abdelfatah#, MD, MS. Baiwen Li#, MD, PhD, Neil Kapil, MD, Alan Noll, MD Lianyong Li, MD, Ph.D. Hui Luo, MD, Huimin Chen, MD, Ph.D, Liang Xia, MD, Ph.D., Xiangbo Chen, Patel Vailshali, MD, Parit Mekaroonkamol, MD, Julia Massaad, MD, Steven Keilin, MD, , Qiang Cai, MD. PHD
Emory University School of Medicine, Division of Digestive Diseases, Atlanta, GA
* This study has been selected to as an oral presentation in DDW 2019 in San Diego in the forum of Cutting Edge of ESD and POEM #
Author share first co-authorship
Corresponding author: Qiang Cai, MD, Ph.D. Professor of Medicine Master Clinician Director, Advanced Endoscopy Fellowship Emory University School of Medicine 1365 Clifton Road, B1262 Atlanta, GA 30322 USA Tel: 404-778-2714 Fax: 404-778-2578 Email: [email protected]
1
Short-term outcomes of double pyloromyotomy versus single pyloromyotomy at peroral endoscopic pyloromyotomy in treatment of gastroparesis (with video) Mohamed M. Abdelfatah, MD, 1# MS. Baiwen Li, MD, PhD, 1,2# Neil Kapil, MD1, Alan Noll, MD, 1 Lianyong Li, MD, Ph.D1,3. Hui Luo, MD1,4, Huimin Chen, MD, Ph.D1,5, Liang Xia, MD, Ph.D. 1,6, Xiangbo Chen MD, 7 Vailshali Patel, MD1, Parit Mekaroonkamol, MD1, Julia Massaad, MD1, Steven Keilin, MD1, Qiang Cai, MD. PHD1
1
Emory University School of Medicine, Division of Digestive Diseases, Atlanta, GA
* This study has been selected to as an oral presentation in DDW 2019 in San Diego in the forum of Cutting Edge of ESD and POEM #
Author share first co-authorship
Current Affiliations: 2. Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 3. Department of Gastroenterology, PLA Strategic Support Force Characteristic Medical Center, Beijing, China 4. State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, China 5. Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
1
6. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University. Nanchang, Jiangxi, China 7. Department of Gastroenteorlogy, Fujian Quanzhou Hospital. Quanzhou, Fujian, China.
Corresponding author: Qiang Cai, MD, Ph.D. Professor of Medicine Master Clinician Director, Advanced Endoscopy Fellowship Emory University School of Medicine 1365 Clifton Road, B1262 Atlanta, GA 30322 USA Tel: 404-778-2714 Fax: 404-778-2578 Email: [email protected]
Author contributions •
MMA assisted in the procedures, collected and analyzed the data, performed statistical work, drafted the paper and implemented all revisions the paper;
•
BL assisted QC in initial concept and design, physically presented in some procedures, assisted in collection, analyzing data, drafting paper and revised the paper;
•
NK, AN assisted in collection and analyzing data and revised the paper;
•
PM, VP and SK assisted in the procedures, interpretation of data and critically revising the intellectual content work it for important; participated discussion and final approval of the version to be published. 2
•
LL, HL, HMC, XL XC, JM physically presented in some procedure, assisted in interpretation of data and critically revising the intellectual content work it for important; participated discussion and final approval of the version to be published.
•
QC obtained IRB, performed the procedure, conceptualized and designed the study, critically revised all the intellectual content of the manuscript; and final approval of the version to be published.
All authors approved the final version of the manuscript.
Disclosures: none Words count: 2256
3
Abstract
Background and Aims: Gastroparesis (Gp) is a chronic debilitating disorder rising in prevalence and hospitalizations. Gastric peroral endoscopic pyloromyotomy (POP or GPOEM) is a novel technique in the treatment of refractory Gp. Despite the initial promising results of GPOEM, one-third of patients do not exhibit any clinical response. Furthermore, loss of clinical response was reported in several studies. No response or loss of response after GPOEM may be related to inadequate myotomy. The aim of our study is to examine whether double pyloromyotomy at GPOEM is superior to single pyloromyotomy.
Method: A retrospective case-controlled study of patients who underwent GPOEM for refractory Gp at our tertiary care institution between June 2015 and March 2018 was performed. Because the follow-up time for the single myotomy group was much longer than that of the doublemyotomy group, we matched the length of follow-up for the single myotomy group to that of the double myotomy group. The outcomes were measured by the changes in Gp cardinal symptom index (GCSI) before and 3 to 6 months after the procedure. Adverse events and other procedural and clinical parameters were also compared.
Results: Ninety patients underwent GPOEM (55 single and 35 double pyloromyotomy) Mean age was 47 ±14 years old, mean duration of symptoms was 5.3 ± 4.4 years. Average GCSI was 3.8 before the GPOEM and the average GCSI 6 months after procedure was 1.8 37 out of 55 (67%) patients underwent single pyloromyotomy achieved clinical response compared with 30 out of 35 (86%) patients receiving double pyloromyotomy. There were no
4
significant differences among procedure time, postoperative pain or length of hospital stay between the 2 groups. There was no difference in adverse events in the 2 pyloromyotomy groups. Conclusion: Double pyloromyotomy is a safe and feasible technique during GPOEM. Clinical success was higher in patients undergoing double pyloromyotomy compared with single pyloromyotomy in this nonrandomized, short-term follow-up study. Long-term studies are needed to further confirm our results.
Keywords: Gastroparesis, POP, Pyloromyotomy, Outcomes, GPOEM
Introduction
Gastroparesis (Gp) is a chronic debilitating disorder with rising prevalence and healthcare burden. (1, 2) Peroral endoscopic pyloromyotomy (POP or GPOEM) adopted the principle of peroral endoscopic myotomy (POEM) for the treatment of achalasia to enable pyloromyotomy by endoscopy in submucosal tunnel. Since it was first reported in 2013 (3), subsequent studies on GPOEM have promisingly reported 62% to 90% success rate in short-term outcomes for Gp patients. (4-18). Other studies have demonstrated that GPOEM improves quality of life and reduces health care utilization in patients with Gp. (12)
Despite the initially promising results of GPOEM, studies showed about one-third of patients did not exhibit clinical response to treatment. Furthermore, partial or complete loss of
5
clinical response during follow-up was reported. (8, 14) One study showed 29% of initial responders may lose clinical response at 2 years postprocedure. (15)
A number of studies have been published which looked at different techniques to improve the outcomes of GPOEM. Full thickness pyloromyotomy was adopted in a few centers. It was reported that full-thickness pyloromyotomy resulted in a high short-term success rates of 81% to 90%, respectively. (10, 17) However, full-thickness pyloromyotomy resulted in a higher rate of intraprocedure bleeding and perforation. In a small study, a 15% rate of perforation was reported.(10)
One theory to explain the lack of initial response or the loss of response in initial GPOEM responders is inadequate pyloromyotomy. In our experience, when Gp symptoms recur, a repeat pyloromyotomy can be performed and still yield an effective result despite technical challenges due to submucosal fibrosis. In the current literature, it is routine to perform only one myotomy. We modified the pyloromyotomy technique by performing 2 separate circular pyloromyotomies, named double pyloromyotomy. We hypothesize that performing double pyloromyotomy at GPOEM can improve outcomes of GPOEM and decrease the recurrence rate after initial response.
Materials and Methods
We conducted a retrospective case-controlled study of consecutive patients who underwent GPOEM for refractory Gp at our institution from June 2015 to March 2019. In our
6
institution, the single circular pyloromyotomy was performed from June 2015 until June 2018. We used the double circular pyloromyotomy technique in all GPOEM patients starting from June 2018. The study was approved by our Institutional Review Board initially on July 25, 2015 and was recently reviewed on July 25, 2019, the IRB number was 00089650.
Because the follow-up time for the single pyloromyotomy group is much longer than that of the double-pyloromyotomy group, in order to make the groups comparable, we matched the follow-up time for the single-pyloromyotomy group to that of the double-pyloromyotomy group to detect initial responders at 3 to 6 months after the procedure. Therefore, we analyzed the outcome data in the single-pyloromyotomy group within the similar length of follow-up.
The procedures were performed mainly by an experienced endoscopist (Q.C.), assisted by a junior faculty or an Advanced Endoscopy fellow in the majority of procedures. Patient characteristics and procedural details were collected. Refractory Gp was defined as gastricemptying study (GES)-confirmed Gp with failure for at least 6 months of dietary modifications and a trial of maximally tolerated doses of prokinetic medications after ruling out mechanical obstruction.
Severity of gastric emptying was graded from 1 to 4 according to gastric retention at 2 or 4 hours as follows: grade 1 (mild), 61% to 70% retention at 2 hours or 11% to 20% retention at 4 hours; grade 2 (moderate), 71% to 80% retention at 2 hours or 21% to 35% retention at 4 hours; grade 3 (severe) 81% to 90% retention at 2 hours or 36% to 50% retention at 4 hours; grade 4 (very severe), 91% to 100% retention at 2 hours or >50% retention at 4 hours. (19, 20) Clinical
7
response was defined as: a decrease of at least 1 point in the average total Gastroparesis Cardinal Symptom Index (GCSI) score with more than a 25% decrease in at least 2 subscales of cardinal symptoms (13).
In our unit, all patients were observed for at least 24 hours after the procedure. A clear liquid diet was initiated the day after the procedure, except for patients with persistent postprocedure pain. For those patients with persistent abdominal pain, abdominal imaging studies, such as upper GI barium study or computed tomography were used to rule out perforation. Patients were discharged the next day with instructions for advancing their diet from liquids to a regular diet over a period of 4 weeks after the procedure.
The protocol of GPOEM was described in detail in our prior studies (11-13). The only difference in this study is adding another myotomy in the double-myotomy group. Briefly, the procedure was performed with a gastroscope (GIF-H190; Olympus, Tokyo, Japan) with a transparent distal cap attachment (MH-588; Olympus, Japan) and Hybrid knife I-type (ERBE, Germany) or a hook knife (Olympus, Japan), using only carbon dioxide for insufflation (UCR, Olympus, Japan). Submucosal tunneling was performed along the posterior wall of the greater curvature of the antrum (3-6 o’clock position) using spray coagulation mode 50 W at effect 2 (ERBE) (Figure 1) After identification of the pyloric ring, a selective circular pyloromyotomy was performed at the 6 or 7 o’clock position in the single pyloromyotomy group, whereas in the double-pyloromyotomy group, another selective cut was performed at the 4 or 5 o’clock position (Figure 1) to keep at least 1 centimeter in between the 2 pyloromyotomies. (Video 1)
8
Descriptive statistics of baseline characteristics were calculated for means and standard deviations. Comparative analyses of pre- and post-GPOEM total GCSI and subscale scores were performed using a repeated measures ANOVA and post-hoc paired t-test. A p-value of less than 0.05 was considered statistically significant for all analyses. Data were analyzed using IBM SPSS Version 22.0 statistical software (IBM Corporation, Armonk, NY, USA)
Results
A total of 90 patients who underwent GPOEM were included in the study; 17 males and 73 females. Mean age was 47 ±14 years old, mean duration of symptoms was 5.3 ± 4.4 years. Average GCSI was 3.8 before the GPOEM (Table. 1). Overall, 67 (74%) patients had adequate clinical response at 3 to 6 months follow-up with the average GCSI improved from 3.8 ± 0.8 to 1.8± 1.4 after GPOEM.
Fifty-five patients had a single pyloromyotomy (40 patients of the single myotomy were previously published mainly comparing the outcome of diabetic and nondiabetic gastroparesis after GPOEM) (11) and 35 had a double pyloromyotomy. There was no difference in patients’ baseline characteristics, severity of delayed gastric emptying, or risk factors (Table 1). There was a significantly higher rate of clinical response in patients who underwent double pyloromyotomy (86%, n= 30/35), compared with (67%, 37 out of 55) those in the singlepyloromyotomy group (p=0.04). (Table 2)
9
In terms of symptomatic improvement, GCSI score improved to 2.1 ± 1.6 in the single pyloromyotomy versus 1.7 ± 1 in the double pyloromyotomy group. There were no significant differences in procedure time between the single-pyloromyotomy and the doublepylorormyotomy group (50.1± 13 versus 49.6 ± 12 minutes). Likewise, there was no difference in length of hospital stay between the 2 groups 1.3 ± 0.7 versus 1.4 ± 0.6 (Table 2, Figure 3). Notably, 2 patients in the single-pyloromyotomy group with initial response who later had recurrent symptoms underwent upper endoscopy revealing a decrease in the diameter of the pylorus opening. Repeat GPOEM showed fibrosis at the myotomy site. The fibrosis may have resulted in stricture of the pyloric ring. Repeat pyloromyotomy resulted in regaining the response in the 2 patients. As shown in Figure 1, the precondition for single or double myotomy is that the pyloric ring is exposed nicely. Based on our experience in the study, double myotomy can be performed in almost all cases without difficulties. Double pyloromyotomy was planned but not performed in only 2 patients who had significant abdominal distention that resulted in difficulty in ventilating the patients, and the anesthesiologist asked us to consider terminating the procedure. In a normal situation, we could suction out air in the stomach lumen and wait for a few minutes for the CO2 to be reabsorbed, then continue the procedure. However, under the study situation, for patients’ safety reasons, we aborted the plan for a second myotomy after a first myotomy had been performed already
There were no reported major adverse events in the double-pyloromyotomy group, compared with 2 in the single-pyloromyotomy group (one incident of tension capnoperitoneum and another of a later bleeding secondary to a mucosotomy site ulcer). The patient with the
10
tension capnoperitoneum was managed by needle decompression and recovered without any consequences, the patient with the bleeding ulcer was managed by endoscopic treatment and oral proton pump inhibitor.
Outcome after consideration of learning curve
One of the major confounders of our results is the potential improvement of our technique and experience with time. However, there is no existing study on the learning curve for GPOEM. We divided the 55 cases with single myotomy into 2 subgroups, the first 27 cases and the later 28 cases and performed a subanalysis to exclude the potential learning effect on the outcome. The clinical response rate for the 2 subgroups were 70% and 64%, respectively, and there were no statistical differences between the 2 (P=0.9). Discussion
Our results suggest a superior short-term (3-6 months) clinical response rate in the patients who underwent double pyloromyotomy compared with single pyloromyotomy. To our knowledge, this is the first study describing the double pyloromyotomy technique and the promising short-term outcome. Furthermore, there were no differences in procedural time, adverse event rates or hospital stay between the 2 groups
The prior literatures indicate that the physiopathology of Gp includes 2 major components. First, an alteration of the gastric motility causes atony of the stomach body, leading to delayed gastric emptying. The second pathophysiologic mechanism underlying Gp is an
11
increase in pyloric tone, which is demonstrated in previous work by Mearin et al. (21) Thus, surgical pyloroplasty and transpyloric stent placement have been shown to be beneficial in early studies. (22,23) All of these results suggest that pyloric spasm has an important role in gastroparetic symptoms. Furthermore, our prior investigation found that when gastroparesis symptoms recur, a repeat pyloromyotomy can be performed and still yield an effective result despite technical challenges due to submucosal fibrosis (11)
There are 2 aspects to improve the outcome of GPOEM. One is to select the appropriate patients who likely will respond to the therapy. There is limited information on the criteria for selecting patients for GPOEM treatment. We tried to divide the patients with Gp into proximal and distal Gp patients by analyzing the image pattern of the gastric emptying study and thereby to facilitate selection of patients before the procedure. The clinical outcome for the first 40 patients showed GPOEM was effective for both diabetic and nondiabetic Gp. (11) Disease duration may affect the outcome of GPOEM: the longer the duration of the disease, the worse the outcome.
The other aspect is to improve the procedural technique by mainly performing an adequate myotomy. In all published studies, it is routine to perform a single myotomy at GPOEM. One of the underlying etiologies of Gp may be the initial immune insult that leads to universal fibrosis and physiologic changes in the GI tract. (11,24) Patients with Gp may have a higher diffuse collagen fibrosis particularly in the pylorus that leads to fibrosis of the pyloromyotomy site in the pyloric muscle. (16, 21) Our results could be explained by the precise disruption of the pyloric ring in 2 locations, resulting in a more effective disruption of the pyloric
12
ring (Figure 3), therefore eliminating or reducing the risk of future fibrotic bridging, stricture or pylorospasm at the pyloromyotomy site. Also, technically, it is safe and feasible to perform double myotomy at GPOEM.
One of the main strengths of our study is the relatively large sample size given the novelty of the procedure. The study design compares all patients in 2 different periods of time, thus eliminating selection bias. Nevertheless, our study has limitations. The retrospective nature of a single center comparing baseline patient characteristics between the 2 groups is subject to confounder bias. One of the most important confounder could be from increased experience over time. We performed subanalysis excluding the potential learning effect on outcome. There was no significant difference between the outcome of our first 27 cases and later 28 cases in the single myotomy group. Our prior study indicated that the learning cases for POEM should be about 20 cases (25). However, at the present time, there are no data on the learning curve for GPOEM. The result did not show any effect of learning curve on the outcome. It could be that the endoscopist (QC) is very experienced in performing POEM, he had already performed at least a hundred POEM procedures before starting GPOEM. However, the retrospective nature of a single center, nonrandomized study comparing baseline patient characteristics between the 2 groups is still subject to confounder bias. The results were suggestive of superiority of the double myotomy only in the short term. It would be interesting to follow these patients and report the recurrence risk in single versus double myotomy in the long term.
In conclusion, double pyloromyotomy during GPOEM is a safe and feasible treatment of Gp with similar procedural time and adverse event rate to that of conventional single
13
pyloromyotomy. However, double pyloromyotomy showed a higher clinical response rate compared with single pyloromyotomy in a 3- to 6-month follow-up period. A larger prospective, randomized study on long-term outcomes is warranted to help refine the technique of this procedure. References 1. Wang YR, Fisher RS, Parkman HP. Gastroparesis-related hospitalizations in the United States: trends, characteristics, and outcomes, 1995–2004. The American journal of gastroenterology. 2008;103:313-22. 2. Jung HK, Choung RS, Locke GR, 3rd, Schleck CD, Zinsmeister AR, Szarka LA, et al. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009;136:1225-33. 3. Khashab MA, Stein E, Clarke JO, Saxena P, Kumbhari V, Roland BC, et al. Gastric peroral endoscopic myotomy for refractory gastroparesis: first human endoscopic pyloromyotomy (with video). Gastrointestinal endoscopy. 2013;5:764-8. 4. Khashab MA, Ngamruengphong S, Carr-Locke D, Bapaye A, Benias PC, Serouya S, et al. Gastric per-oral endoscopic myotomy for refractory gastroparesis: results from the first multicenter study on endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017;85:123-8. 5. Chen H, Cai Q. Gastroparesis: Current Opinions and New Endoscopic Therapies. Gastrointest Endosc Clin N Am. 2019;29:xv-xvi. 6. Chaves DM, de Moura EG, Mestieri LH, Artifon EL, Sakai P. Endoscopic pyloromyotomy via a gastric submucosal tunnel dissection for the treatment of gastroparesis after surgical vagal lesion. Gastrointest Endosc. 2014;80:164. 7. Chung H, Dallemagne B, Perretta S, Lee SK, Shin SK, Park JC, et al. Endoscopic pyloromyotomy for postesophagectomy gastric outlet obstruction. Endoscopy. 2014;46 Suppl 1 UCTN:E345-6. 8. 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;44:169-73. 9. Kahaleh M, Gonzalez JM, Xu MM, Andalib I, Gaidhane M, Tyberg A, et al. Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: a multicenter international experience. Endoscopy. 2018;50:1053-8. 10. Rodriguez JH, Haskins IN, Strong AT, Plescia RL, Allemang MT, Butler RS, et al. Per oral endoscopic pyloromyotomy for refractory gastroparesis: initial results from a single institution. Surg Endosc. 2017;31:5381-8. 11. Mekaroonkamol P, Patel V, Shah R, Li B, Luo H, Shen S, et al. Association between duration or etiology of gastroparesis and clinical response after gastric per-oral endoscopic pyloromyotomy. Gastrointest Endosc. 2019.
14
12. Mekaroonkamol P, Dacha S, Wang L, Li X, Jiang Y, Li L, et al. Gastric Peroral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of Life, and Reduces Health Care Use For Patients With Gastroparesis. Clin Gastroenterol Hepatol. 2019;17:82-9. 13. Dacha S, Mekaroonkamol P, Li L, Shahnavaz N, Sakaria S, Keilin S, et al. Outcomes and quality-of-life assessment after gastric per-oral endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017;86:282-9. 14. 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;46:364-70. 15. Mohamed M. Abdelfatah PM, Neil Kapil, Alan Noll, Huimin Chen Hui Luo, Nikrad Shahnavaz, Steven Keilin, Field Willingham, Jennifer Christie, Qiang Cai. Long term outcome of Gastric Per Oral Endoscopic Pyloromyotomy in treatment of Gastroparesis: A single center experience [abstract]. Gastrointest Endosc 2019;89:AB102. 16. Mekaroonkamol P, Shah R, Cai Q. Outcomes of per oral endoscopic pyloromyotomy in gastroparesiss worldwide. World J Gastroenterol. 2019;25:909-922 17. Jacques J, Pagnon L, Hure F, Legros R, Crepin S, Fauchais AL, et al. Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: prospective trial with assessment of pyloric function. Endoscopy. 2019;51:40-9. 18. Xu J, Chen T, Elkholy S, Xu M, Zhong Y, Zhang Y, et al. Gastric Peroral Endoscopic Myotomy (G-POEM) as a Treatment for Refractory Gastroparesis: Long-Term Outcomes. Can J Gastroenterol Hepatol. 2018;2018:6409698. 19. Rao SS, Camilleri M, Hasler WL, Maurer AH, Parkman HP, Saad R, et al. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterol Motil. 2011;23:8-23. 20. Moraveji S, Bashashati M, Elhanafi S, Sunny J, Sarosiek I, Davis B, et al. Depleted interstitial cells of Cajal and fibrosis in the pylorus: Novel features of gastroparesis. Neurogastroenterol Motil. 2016;28:1048-54. 21. Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986;90:1919-25. 22. Hibbard ML, Dunst CM, Swanstrom LL. Laparoscopic and endoscopic pyloroplasty for gastroparesis results in sustained symptom improvement. J Gastrointest Surg. 2011;15(9):15139. 23. Khashab MA, Besharati S, Ngamruengphong S, Kumbhari V, El Zein M, Stein EM, et al. Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video). Gastrointest Endosc. 2015;82:1106-9. 24. Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, Smyrk TC, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140:1575-85 e8. 25. Dacha S, Mekaroonkamol P, Wang L, Li XY, Jiang YP, Phillips, G, Keilin, S, Willingham, FF, Cai, Q. Outcome and quality of lefe assessment after per oral endosocpic myotomy (POEM) performed in the endosocooy unit with trainees. Srugical Endoscopy. 2018;32:3046-54
15
Table 1. Perioperative baseline characteristics. Single
Double
P value
pyloromyotomy
pyloromyotomy
N= 55
N= 35
Age, mean (SD)
47.9 ±13
47.2 ±14
0.85
Female sex n (%)
46
27
0.46
Post- GPOEM Body mass index (kg/m2)
27 ± 7.7
28 ± 11
0.8
Duration of gastroparesis (Y)
6.3 ± 4.9
4.9 ± 3.9
0.20
Diabetes mellitus
21
17
0.14
Idiopathic
27
18
Postsurgical
7
0
Pre-GPOEM GCSI score (SD)
3.9 ± 0.9
3.7 ± 0.7
0.53
Pre-GPOEM GCSI score nausea vomiting
4.1 ± 1.2
4.3 ± 0.9
0.47
Pre-GPOEM GCSI score early satiety
3.6 ± 1.4
3.5 ± 1
0.78
Pre-GPOEM GCSI score bloating
3.7 ± 1.5
3.2 ± 1.3
0.1
Etiology
GES grades Grade 1
0.4 14%
7%
16
Grade 2
34%
17%
Grade 3
26%
37%
Grade 4
26%
29%
Tube feeding pre GPOEM
7
4
0.2
Gastric stimulator
8
3
0.2
History of chronic pain
29
15
0.06
Non-narcotic pain medication
7
5
0.4
Psychiatric history
34 (61)
12 (34)
0.02
Abbreviations SD: standard deviation, N: Number P values <.05 are bolded as statistically significant. GE, gastric emptying; GCSI, gastroparesis cardinal symptom index
17
Table 2: Study clinical outcomes Single
Double
P value
pyloromyotomy
pyloromyotomy
N= 55
N= 35
Adverse events
2
0
Number of clips used mean
4.3 ± 0.8
4.8 ± 7
0.56
Procedure time, mins (SD)
50.1± 13
49.6 ± 12
0.40
1.3 ± 0.7
1.4 ± 0.6
0.55
Post- GPOEM Body mass index
27.7 ± 11
27.6 ± 7.7
0.9
Post-POP GCSI score (SD)
2.1 ± 1.6
1.7 ± 1.1
0.10
Clinical Success at 3-6 months follow-up
37 (67%)
30 (86%)
0.04*
Recurrence 1-6 months
4 (7%)
1 (2.9%)
0.3
Procedural Factors
In-hospital outcomes Length of stay, days (SD) Treatment outcomes
Abbreviations SD: standard deviation, N: Number P values <.05 are bolded as statistically significant. gastric emptying; GCSI, gastroparesis cardinal symptom index; NV, nausea and vomiting.
18
Figure Legends: Figure 1. Pyloromyotomy sites. Pyloric ring with yellow arrow pointing at the pyloromyotomy site at 3 and 6 o’clock. Figure 2. Outcomes of single and double myotomy at GPOEM. A, Average GCSI changes after single and double myotomy. B, Clinical success after single and double myotomy Figure 3. Endosocpic views of double and single pyloromyotomy. A, Single pyloromyotomy at 6 o’clock. B, Endoscopic view after the first myotomy. C, Double myotomy at 3 and 6 o’clock. D, Endoscopic view after the double myotomy.
19
Gp: gastroparesis, GPOEM; gastric peroral endoscopic pyloromyotomy,
1