Clinical Gastroenterology and Hepatology 2020;-:-–- 1 59 2 60 3 61 4 62 5 Long-Term Outcome of Gastric Per-Oral Endoscopic 63 6 64 7 Pyloromyotomy in Treatment of Gastroparesis 65 8 66 9 Q9 Mohamed M. Abdelfatah, Alan Noll, Neil Kapil, Rushikesh Shah, Lianyong Li, 67 10 Rosemary Nustas, Baiwen Li, Hui Luo, Huimin Chen, Liang Xia, 68 11 Parit Mekaroonkamol, Nikrad Shahnavaz, Steven Keilin, Field Willingham, 69 12 Jennifer Christie, and Qiang Cai 70 13 71 14 72 Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia 15 73 16 74 BACKGROUND & AIMS: Gastric per oral endoscopic pyloromyotomy (GPOEM) is a promising treatment for gastro- 17 paresis. There are few data on the long-term outcomes of this procedure. We investigated long- 75 18 term outcomes of GPOEM treatment of patients with refractory gastroparesis. 76 19 77 20 METHODS: We conducted a retrospective case-series study of all patients who underwent GPOEM for re- 78 21 fractory gastroparesis at a single center (n [ 97), from June 2015 through March 2019; 90 79 22 patients had more than 3 months follow-up data and were included in our final analysis. We 80 23 collected data on gastroparesis cardinal symptom index (GCSI) scores (measurements of 81 24 postprandial fullness or early satiety, nausea and vomiting, and bloating) and SF-36 question- 82 25 naire scores (measures quality of life). The primary outcome was clinical response to GPOEM, 83 26 defined as a decrease of at least 1 point in the average total GCSI score with more than a 25% 84 fi 27 decrease in at least 2 subscales of cardinal symptoms. Recurrence was de ned as a return to 85 28 baseline GCSI or GCSI scores of 3 or more for at least 2 months after an initial complete 86 response. The secondary outcome was the factors that predict GPOEM failure (no response or 29 87 gastroparesis recurrence within 6 months). 30 88 31 89 RESULTS: At initial follow-up (3 to 6 months after GPOEM), 73 patients (81.1%) had a clinical response 32 and significant increases in SF-36 questionnaire scores (indicating increased quality of life) 90 33 whereas 17 patients (18.9%) had no response. Six months after GPOEM, 7.1% had recurrence. 91 34 At 12 months, 8.3% of patients remaining in the study had recurrence. At 24 months, 4.8% of 92 35 patients remaining in the study had a recurrence. At 36 months, 14.3% of patients remaining in 93 36 the study had recurrence. For patients who experienced an initial clinical response, the rate of 94 37 loss of that response per year was 12.9%. In the univariate and multivariate regression anal- 95 38 ysis, a longer duration of gastroparesis reduced the odds of response to GPOEM (odds ratio 96 39 [OR], 0.092; 95% CI, 1.04–1.3; P [ .001). On multivariate logistic regression, patients with high 97 – [ 40 BMIs had increased odds of GPOEM failure (OR, 1.097; 95% CI, 1.022 1.176; P .010) and 98 41 patients receiving psychiatric medications had a higher risk of GPOEM failure (OR, 1.33; 95% CI, 99 0.110–1.008; P [ .052). 42 100 43 101 CONCLUSIONS: In retrospective analysis of 90 patients who underwent GPOEM for refractory gastroparesis, 44 102 81.1% had a clinical response at initial follow-up of their procedure. 1 year after GPOEM, 69.1% 45 of all patients had a clinical response and 85.2% of initial responders maintained a clinical 103 46 response. Patients maintained a clinical response and improved quality of life for as long as 3 104 47 years after the procedure. High BMI and long duration gastroparesis were associated with 105 48 failure of GPOEM. 106 49 107 50 Keywords: Therapy; Diabetes; Gastric Emptying; Psychologic. 108 51 109 52 110 53 111 54 112 55 113 Abbreviations used in this paper: BMI, body mass index; GCSI, Gastro- 56 paresis Cardinal Symptom Index; GE, gastric emptying; GES, gastric 114 57 electrical stimulators; GP, gastroparesis; GPOEM, gastric per-oral endo- © 2020 by the AGA Institute 115 scopic pyloromyotomy; ICC, interstitial cells of Cajal; J-tube, jejunostomy 1542-3565/$36.00 58 tube; SF-36, Short Form-36. https://doi.org/10.1016/j.cgh.2020.05.039 116 Downloaded for Anonymous User (n/a) at University of Alabama at Birmingham from ClinicalKey.com by Elsevier on November 03, 2020. For personalFLA 5.6.0 use only. DTD No other YJCGH57249_proof uses without permission. Copyright 22 July ©2020. 2020 Elsevier 7:47 Inc. pm All rights ce CJ reserved. 2 Abdelfatah et al Clinical Gastroenterology and Hepatology Vol. -, No. - 117 Q6 Q5 astroparesis (GP) is a chronic, debilitating motility 175 118 Gdisorder characterized by nausea, vomiting, early What You Need to Know 176 119 satiety, and postprandial fullness.1,2 In 2007, the age- 177 Background 120 adjusted prevalence of GP per 100,000 persons was 178 121 approximately 4-fold higher in women than men: 37.8 Gastric per oral endoscopic pyloromyotomy 179 122 and 9.6, respectively.3 Furthermore, incidence of GP hos- (GPOEM) is a promising treatment for gastroparesis, 180 123 pitalization seems to be rising, reported as high as a yet there are few data on the long-term outcomes of 181 124 300% increase from 1997 to 2013, with an estimated this procedure. 182 4 125 annual health care cost of $568 million. GP can have a Findings 183 126 significant adverse impact on the overall quality of life In retrospective analysis of 90 patients who under- 184 5 127 of the affected patient. No definitive cure for GP went GPOEM for refractory gastroparesis, 80% had 185 128 currently exists with most available treatment options an initial clinical response and more than 90% 186 129 focusing on symptom control with diet modification maintained that response 1 year after the procedure. 187 130 and prokinetic medications. Unfortunately, prokinetic Patients maintained a clinical response and 188 131 medication use is often limited by possible dangerous improved quality of life for as long as 3 years after 189 132 side effects including arrhythmia, tardive dyskinesia, the procedure. 190 133 and tachyphylaxis. 191 134 Gastric electrical stimulators (GES) are an interven- Implications for patient care 192 135 tional therapeutic option, particularly for nausea- GPOEM minimize health care utilization and improve 193 136 predominant GP in patients with diabetes; however, ef- the long term quality of life of patient with refractory 194 137 ficacy of such devices has proven underwhelming.6 It is gastroparesis. High body mass index and long 195 138 estimated that 20% of patients receive no benefit from duration gastroparesis are associated with failure of 196 139 such devices, with open-label studies reporting 1-year GPOEM—these factors should be considered when 197 140 clinical response rates between 45% and 74%.7–13 selecting treatment for patients with gastroparesis. 198 141 Durability of clinical response further limits broad 199 142 adoption of this technology with 1 study reporting only 200 143 25% of patients who found clinical benefit maintaining to evaluate the long-term outcomes of GPOEM in treat- 201 144 response at 3 years and only 26% and 44% of patients ment of patients with refractory GP and identify factors 202 145 reporting reductions in nausea and vomiting, respec- that predict failure of GPOEM. 203 146 tively, at 10 years. In addition to the need for laparo- 204 147 scopic implantation of the device and removal before Materials and Methods 205 148 magnetic resonance imaging, device-related complica- 206 149 tions are reported in 15% of patients. These include 207 After approval by the institutional review board at 150 bowel obstruction, perforation, lead migration, and 208 Emory University, we conducted a retrospective case series 151 wound complications. Complications are associated with 209 – of all patients who underwent GPOEM for refractory GP 152 a removal rate of 6.3%–12.8%.8 10,12,14 210 between June 2015 and March 2019. The procedures were 153 Another therapeutic intervention is pyloric disruptive 211 performed by an endoscopist experienced with the pro- 154 therapy. Laparoscopic pyloromyotomy has been shown 212 cedure and typically assisted by an advanced endoscopy 155 to improve symptom scores by 83%–86% and improves 213 fellow. The Gastroparesis Cardinal Symptom Index (GCSI) 156 or normalizes gastric emptying (GE) in nearly 60%–90% 214 score was calculated by averaging the mean score of 3 157 of GP patients.15 Widespread use of this surgical 215 subscales: (1) postprandial fullness/early satiety, (2) 158 approach is limited by postoperative adverse events 216 nausea/vomiting, and (3) bloating.28 Eight aspects of 159 including leaks, suture line bleeding, and wound in- 217 quality of life, including physical functioning, role limitation 160 fections.15 Alternatively, gastric per-oral endoscopic 218 caused by physical health, bodily pain, general health, vi- 161 myotomy (GPOEM) is an endoscopic pyloric disruptive 219 tality, social functioning, role limitation caused by 162 therapy for GP wherein a submucosal tunnel is created to 220 emotional problems, and mental health were assessed us- 163 approach and then myotomize the pyloric muscle. 221 ing the Short Form-36 (SF-36) questionnaire. The scores 164 GPOEM was debuted in 2013 following the adoption of 222 were calculated using a revised International Resource 165 per-oral endoscopic myotomy for treatment of acha- 223 Center for Health Care Assessment scoring system and 166 lasia.8 Since that time, several studies have reported an 224 reported as a median of each category. An average score of 167 average of 83.9% (62%–90%) short-term (6 months to 1 225 – all 8 domains was used to assess the overall quality of life 168 year) clinical success on GPOEM in GP patients.16 26 226 similar to our previous publication.29,30 169 Benefits of GPOEM over laparoscopic pyloroplasty 227 170 include shorter operative time, less intraprocedural 228 171 blood loss, and a shorter length of stay.27 Definitions 229 172 Despite the initial promising short-term results, proof 230 173 of longer-term outcome is fundamental for wider adop- Refractory gastroparesis.