Management of reflux after peroral endoscopic myotomy
Review Article

Management of reflux after peroral endoscopic myotomy

Zachary M. Callahan, Bailey Su, Michael Ujiki

Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA

Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Zachary M. Callahan, MD. General Surgery Resident, Department of Surgery, Northshore University HealthSystem, 2650 Ridge Ave, Evanston, IL 60201, USA. Email: zmcallahan@gmail.com.

Abstract: Peroral endoscopic myotomy (POEM) has emerged as an attractive treatment option for patients suffering from achalasia. The endoscopic nature of the procedure prevents an accompanying fundoplication to decrease post-procedure gastroesophageal reflux (GER). A large amount of literature exists reporting incidence of post-POEM GER but differences in the metric used to report GER, short follow-up and infrequent objective measuring creates wide variation in this data. Moderately sized multi-institutional trials and meta-analysis that use the most sensitive metric of GER suggest the incidence is close to 50%, which is significantly higher than traditional Heller myotomy with fundoplication. Although chronic GER has serious risks and implications in this patient population, many studies report complete subjective and objective resolution with anti-reflux medications. Novel endoscopic fundoplication technologies are emerging but their role in post-POEM GER is yet to be determined.

Keywords: Peroral endoscopic myotomy (POEM); reflux; myotomy; Heller


Received: 30 October 2018; Accepted: 14 January 2019; Published: 01 February 2019.

doi: 10.21037/jxym.2019.01.02


Introduction

Heller myotomy has long been established as effective surgical treatment for achalasia. Soon after the procedure’s adoption, reports of postoperative pathologic gastroesophageal reflux (GER) created controversy among surgeons; some surgeons attributed reflux to an overzealous myotomy while others insisted that it was an unavoidable result of the procedure (1-4). Reflux after myotomy makes physiologic sense because although obliterating the lower esophageal sphincter allows passage of food and resolution of dysphagia, it also weakens the anatomic mechanism that protects the distal esophagus from caustic gastric contents. The controversy was ultimately settled after numerous studies demonstrated the necessity of an accompanied fundoplication during myotomy; fundoplication effectively reduced post-operative GER without affecting dysphagia scores or recurrence (5-10).

Interestingly, the impressive technologic and technical advent of the peroral endoscopic myotomy (POEM), an incisionless procedure that boasts a comparable success and complication rate as Heller myotomy (11-13), has resurfaced the problem encountered by the first esophagomyotomy surgeons twenty years earlier. The endoscopic nature of the procedure prevents a concomitant anti-reflux procedure. Additionally, some argue that this approach does not necessarily warrant an anti-reflux procedure, as the spared longitudinal muscles fibers, intact phrenoesophageal ligament, and preserved nervous complex of the gastroesophageal (GE) junction protect against significant reflux (14-18). This review will discuss the definition, incidence, diagnosis, implications, and treatment of post-POEM GER.


Definition

Before discussing the incidence of post-POEM GER, it is important to acknowledge the variation in how GER is measured across studies and recognize that this may account for the wide range of incidence reported in the literature. Assessments may include symptom questionnaires, proton pump inhibitor (PPI) use, endoscopic evidence of reflux esophagitis, or 24-hour pH abnormalities. Thus, it is no surprise that large meta-analyses differ depending on which metric is used (19). In fact, the most objective measure of GER, abnormal pH levels, tends to be the least reported outcome metric after POEM (13,20). Additionally, some selection bias where only symptomatic patients undergo testing, may further obscure the data. Lastly, the relative novelty of POEM prevents a fair long-term comparison to laparoscopic Heller myotomy (LHM) and long-term incidence of GER after POEM remains unknown.


Incidence and diagnosis of reflux

Symptoms

The greatest amount of literature on post-POEM GER uses symptoms as a marker of reflux (Table 1). Most studies use clinical symptoms such as regurgitation, heartburn, and retrosternal pain, though some have adopted standardized reflux score such as GERDQ, GERSS, and GERD-HRQL. Interestingly, many patients experience these symptoms pre-operatively as a result of achalasia and it is unclear how this affects the true rate of reflux. In the current literature, post-POEM GER ranges from 6% to 37%. Studies with the largest sample sizes (n>100) place the incidence between 16–22% (17,21-25). A true conclusion from this data should be drawn carefully, as the majority of POEM studies have less than 1-year follow-up. Additionally, some but not all patients are discharged on varying lengths and doses of PPI prophylaxis, which may alter symptomatology. Recently, a large meta-analysis using 2,142 patients with an average of 7.6 months of follow-up after POEM, found the incidence of symptomatic GER to be lower, at 8.8% (20). This discrepancy may be partially explained by the predominantly Asian populations in many of these studies; Asian countries have lower prevalence of GER and less GER-pathogenetic factors such as different lifestyles and eating habits (32).

Table 1
Table 1 Patients reporting symptomatic reflux after POEM, excluding studies with n<50, follow-up <3 months (16,17,21-31)
Full table

Even if symptomatic GER after POEM is as low as 8.8%, it is important to recognize that the correlation between symptomatic and pathologic GER, evidenced by esophagogastroduodenoscopy (EGD) or pH monitoring, is questionable. Jones et al. (33) tested for correlation between GERSS/GERD-HRQL surveys and pH testing in 43 patients after POEM. They found poor correlation with either survey; most alarming was that asymptomatic patients comprised 50% of those with pathologic acid reflux. Multiple other studies demonstrated similar findings (23,34-38). The variation in methods of measuring symptoms as well as poor correlation of symptoms to pathologic GER suggests that the best measure of post-POEM GER is not subjective, but objective.

Esophagitis

Esophagitis diagnosed on endoscopy works nicely as an objective measure of pathologic GER. In POEM literature, esophagitis is most commonly measured with the Los Angeles (LA) classification during endoscopy (Table 2). The classification groups the degree of esophageal erosion into mild (A, B) and more severe (C, D). In large studies that impose universal post-POEM endoscopy, the rate of esophagitis ranges from 6 to 64.7% (Table 3). It is important to note that although all these studies required post-procedure EGD regardless of symptoms, not all had 100% compliance and thus some bias affects this data; a patient who is having symptoms of reflux is more likely to be willing to undergo endoscopy than a patient who is asymptomatic. Regardless, the rate of esophagitis is quite high across these studies but the majority of patients exhibited only mild esophagitis (class A or B). The meta-analysis by Akintoye et al. again seems to settle a bit lower than the rest of the literature. They found the average incidence of esophagitis in 1,762 patients to be 13% with 8.4-month follow-up. Using esophagitis on EGD as a marker for GER is imperfect as the grading is somewhat subjective and it requires an invasive procedure with inherent risks. Additionally, one could argue that esophagitis is actually the consequence of reflux and thus not the most sensitive marker; the most sensitive marker would objectively detect reflux in real-time.

Table 2
Table 2 Los Angeles classification of esophagitis based on endoscopy
Full table
Table 3
Table 3 Patients with esophagitis by EGD after POEM, excludes studies with n<50 (21-27,29-31,39)
Full table

pH monitoring

Schlottman et al., in a large meta-analysis, reminds physicians that POEM is a new technology and thus should be evaluated with the most sensitive and accurate test (13). Exposure of the esophagus to gastric contents is most accurately measured by pH probe studies. The invention of wireless probes that can collect up to 96 hours of data has allowed an increasing amount of post-POEM pH data to emerge. Most post-POEM studies use a DeMeester score of greater than 14.7 or an esophageal pH of less than 4 for greater than 5% of the study period to classify as abnormal acid exposure, which is consistent with non-POEM-related GER literature. Incidence of abnormal pH studies in POEM patients ranges from 15–88% (Table 4). This parameter, more so than symptoms of esophagitis, is affected by smaller sample size (n=23–103) and short follow-up (only two studies with a mean follow up of greater than 10 months). The Akintoye meta-analysis estimates abnormal acid exposure of 47% in 336 patients at an average follow-up for 8.6 months. It should be emphasized that the most objective, sensitive test for post-POEM GER not only demonstrates an alarmingly high rate of GER but that both symptomatic and endoscopic markers seem to drastically underestimate it.

Table 4
Table 4 Patients with abnormal pH testing after POEM, excluding studies with n<20 (23,25,27,33,35,38-42)
Full table

Rate of GER in LHM; how does POEM compare?

Despite the seemingly high rate of GER after POEM, it is important to remember that myotomy even with fundoplication has a fairly high rate of post-procedure GER as well. Studies examining GER after LHM suffer from the same pitfalls that afflict post-POEM studies. Multi-institutional studies that use abnormal pH as a marker for GER place the true incidence of GER after LHM as high as 21–42% (43-45). A well-executed retrospective review of prospectively collected data by Bhayani et al. (40) demonstrated similar incidence of GER after LHM and POEM as assessed by 24-hour pH studies (32% LHM vs. 39% POEM; P=0.7) and other studies corroborate these findings (11,12,46).

Despite this, the two largest and most recent meta-analyses designed to address this question suggest that the rate of post-POEM GER is significantly higher than for LHM, as many surgeons originally suspected (13,47). Table 5 summarizes the results from Repici et al., which demonstrated significantly higher rates of GER across subjective and objective markers for POEM patients when compared to LHM. Analysis from Schlottman et al. (13) tells a similar story. POEM was found to have significantly higher rates of esophagitis on EGD (22.4% POEM vs. 11.5% LHM) and abnormal acid exposure in pH studies (47.5% in POEM vs. 11.1% in LHM). Both analyses include thousands of patients and likely represent the most accurate estimate of post-POEM GER in comparison to LHM.

Table 5
Table 5 GERD after per-oral endoscopic myotomy as compared with Heller myotomy with fundoplication: a systematic review with meta-analysis by Repici et al. 2018 (47)
Full table

Implications of post-POEM GER

Regardless of variation in the reported incidence of post-POEM GER, it is undeniable that reflux after POEM affects a sizeable number of patients and the clinical implications of this are yet to be determined. This is particularly important as most long-term failures after treatment of achalasia are related to complications of reflux (36). Perhaps the more concerning risk is that of Barrett’s esophagus and progression to esophageal adenocarcinoma. Leeuwenburgh et al. examined a cohort of achalasia patients treated with pneumatic dilation at an impressive 8.9 years of average follow-up. They found that 8.4% of their cohort developed Barrett’s esophagus and 7% of that group developed esophageal adenocarcinoma (48). Studies looking specifically at rates of Barrett’s esophagus after POEM are sparse but early results seem to suggest that this is more than just a theoretical risk (26). In fact, the implications of post-POEM GER are so great that a recent publication in Endoscopy asked if reflux has the potential to “kill POEM” and warned surgeons to monitor these patients carefully (19).


Treatment of post-POEM GER

In almost all studies where post-POEM GER was diagnosed, patients were treated with PPIs. Numerous studies conclude that GER was easily controlled in this manner with symptom resolution in all patients (16,20,21,27,28,38,49-53). Additionally, a handful of studies documented objective evidence of GER resolution with PPI treatment, usually by repeat EGD (23,35,36,54). These studies varied in terms of PPI dosing and length of therapy but most used double dose PPI for 6 weeks if endoscopic esophagitis was found.

With such a high efficacy of PPIs in post-POEM GER, a logical conclusion might be to universally prescribe PPIs for POEM patients. Lifelong PPI therapy has drawbacks however. Firstly, patient compliance is a major issue especially because the majority of these patients are asymptomatic. Additionally, there are increasing concerns for serious side effects with long-term PPI use secondary to vitamin deficiencies, bone fractures, kidney disease, community acquired pneumonia, and increasing rates of Clostridium difficile infections (55-59).

The barriers to medical treatment of post-POEM GER might make surgical treatment a reasonable option. If a patient’s reflux is severe and refractory, one could certainly offer a laparoscopic fundoplication; this has been demonstrated to be a safe and successful treatment method in a handful of patients (60,61). Obviously, requiring a laparoscopic procedure after POEM is not ideal and obviates the endoscopic benefit of the initial procedure.

An endoscopic fundoplication would be most ideal and the relatively novel transoral incisionless fundoplication (TIF) is an attractive option (Esophyx; EndoGastric Solutions, Redmond, WA, USA). This fully endoscopic procedure creates an anti-reflux barrier through creation of a valve 2 to 4 cm in length with a 270 degree or greater circumferential wrap (62). A 2013 systematic review of 551 patients with GER who underwent TIF demonstrated a PPI discontinuation rate of 67% and a 72% patient satisfaction rate. Unfortunately, pH metrics failed to show normalization in this group (63). Notwithstanding, using TIF to treat post-POEM GER has been published in a small case series. Tyberg et al. demonstrated 100% PPI discontinuation in five patients that underwent TIF after POEM. At 3-month EGD, all patients had resolution of esophagitis. Unfortunately, pH metrics after TIF were not measured (64).

Other endoscopic options for GER management exist and could theoretically be used to treat post-POEM GER. The Stretta system (Restech Mederi-RF, Houston, TX, USA) uses radiofrequency ablation to create thermal effect below the mucosa at the GE junction and restore the reflux barrier (65). In non-POEM patients, this technology has been fairly well studied. A recent meta-analysis by Fass et al., containing 2,468 patients (4 randomized controlled trials, 23 cohort studies, and 1 international registry) showed that Stretta improved GERD-HRQL score by 14.6 points (P<0.001) and 51% of patients discontinued PPIs (P<0.001). In a smaller subset of patients, Stretta lowered the incidence of esophagitis by 24% (P<0.001) and DeMeester score by 13.79 (P<0.001) (66). Data looking at Stretta specifically for post-POEM GER has yet to be published.

The Anti-Reflux Mucosectomy (ARMS) involves endoscopic resection of gastric and esophageal mucosa in crescentic fashion which causes remodeling of the gastric cardia flap valve (67). There is little literature on outcomes but the pilot study is encouraging, showing significant improvement in abnormal acid exposure as documented by pH monitoring. Other therapies involving electrical stimulation and magnets are emerging in animal models as well (68,69). It is important to remember that the goal of treating post-POEM GER is objective improvement in reflux because subjective markers in achalasia patients are inconsistent and inaccurate. None of the endoscopic therapies presented above have demonstrated efficacy to this regard leading some to argue that none of them are indicated after POEM until more data become available. To this same end, no endoscopic GER therapy, except for a small case series of TIF patients, has been used in post-POEM GER specifically, and thus the safety and efficacy in this patient population remains unknown.


Recommendations

The post-POEM GER literature suffers from wide variation in methods of measuring GER and thus the true incidence of reflux in these patients is unknown. However, in summating large multicenter studies and current meta-analyses, a significant proportion, possibly more than half of POEM patients, will have pathologic reflux as documented by the most sensitive marker, pH monitoring. This incidence is likely higher than that seen in the current standard, LHM. Thus, the authors conclude that all patients who undergo POEM should be discharged on daily PPI for 6 to 12 months followed by a 96-hour pH study. If the study is positive, then the standard of care is to continue PPI or undergo a laparoscopic anti-reflux procedure in addition to screening EGD every 5 years. If the pH test is negative, the PPI is stopped and repeat testing is only done for patients who develop symptoms. This group should also undergo EGD every 5 years. Similar standards are being adopted by many major medical centers across the world and has the potential to prevent serious complications of uncontrolled post-POEM GER (26,33,34,36,39,41,47).


Acknowledgements

None.


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.


References

  1. Csendes A. Results of surgical treatment of achalasia of the esophagus. Hepatogastroenterology 1991;38:474-80. [PubMed]
  2. Streitz JM, Ellis FH, Williamson WA, et al. Objective assessment of gastroesophageal reflux after short esophagomyotomy for achalasia with the use of manometry and pH monitoring. J Thorac Cardiovasc Surg 1996;111:107-12; discussion 112. [Crossref] [PubMed]
  3. Jara FM, Toledo-Pereyra LH, Lewis JW, et al. Long-term results of esophagomyotomy for achalasia of esophagus. Arch Surg 1979;114:935-6. [Crossref] [PubMed]
  4. Pellegrini C, Wetter LA, Patti M, et al. Thoracoscopic esophagomyotomy. Initial experience with a new approach for the treatment of achalasia. Ann Surg 1992;216:291-6; discussion 296. [Crossref] [PubMed]
  5. Falkenback D, Johansson J, Öberg S, et al. Heller’s esophagomyotomy with or without a 360° floppy Nissen fundoplication for achalasia. Long-term results from a prospective randomized study. Dis Esophagus 2003;16:284-90. [Crossref] [PubMed]
  6. Richards WO, Torquati A, Holzman MD, et al. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: a prospective randomized double-blind clinical trial. Ann Surg 2004;240:405-12; discussion 412. [Crossref] [PubMed]
  7. Burpee SE, Mamazza J, Schlachta CM, et al. Objective analysis of gastroesophageal reflux after laparoscopic heller myotomy: an anti-reflux procedure is required. Surg Endosc 2005;19:9-14. [Crossref] [PubMed]
  8. Campos GM, Vittinghoff E, Rabl C, et al. Endoscopic and surgical treatments for achalasia: a systematic review and meta-analysis. Ann Surg 2009;249:45-57. [Crossref] [PubMed]
  9. Patti MG, Pellegrini CA, Horgan S, et al. Minimally invasive surgery for achalasia: an 8-year experience with 168 patients. Ann Surg 1999;230:587-93; discussion 593. [Crossref] [PubMed]
  10. Salvador R, Pesenti E, Gobbi L, et al. Postoperative Gastroesophageal Reflux After Laparoscopic Heller-Dor for Achalasia: True Incidence with an Objective Evaluation. J Gastrointest Surg 2017;21:17-22. [Crossref] [PubMed]
  11. Marano L, Pallabazzer G, Solito B, et al. Surgery or Peroral Esophageal Myotomy for Achalasia: A Systematic Review and Meta-Analysis. Medicine 2016;95:e3001. [Crossref] [PubMed]
  12. Awaiz A, Yunus RM, Khan S, et al. Systematic Review and Meta-Analysis of Perioperative Outcomes of Peroral Endoscopic Myotomy (POEM) and Laparoscopic Heller Myotomy (LHM) for Achalasia. Surg Laparosc Endosc Percutan Tech 2017;27:123-31. [Crossref] [PubMed]
  13. Schlottmann F, Luckett DJ, Fine J, et al. Laparoscopic Heller Myotomy Versus Peroral Endoscopic Myotomy (POEM) for Achalasia: A Systematic Review and Meta-analysis. Ann Surg 2018;267:451-60. [Crossref] [PubMed]
  14. Vigneswaran Y, Ujiki MB. Peroral endoscopic myotomy: An emerging minimally invasive procedure for achalasia. World J Gastrointest Endosc 2015;7:1129-34. [Crossref] [PubMed]
  15. Perretta S. Management of Gastric Reflux Following Per-Oral Endoscopic Myotomy. In: Reavis KM. editor. Per oral endoscopic myotomy (POEM). Cham: Springer International Publishing, 2017:159-75.
  16. Ling TS, Guo HM, Yang T, et al. Effectiveness of peroral endoscopic myotomy in the treatment of achalasia: a pilot trial in Chinese Han population with a minimum of one-year follow-up. J Dig Dis 2014;15:352-8. [Crossref] [PubMed]
  17. Hungness ES, Sternbach JM, Teitelbaum EN, et al. Per-oral Endoscopic Myotomy (POEM) After the Learning Curve: Durable Long-term Results With a Low Complication Rate. Ann Surg 2016;264:508-17. [Crossref] [PubMed]
  18. von Renteln D, Inoue H, Minami H, et al. Peroral endoscopic myotomy for the treatment of achalasia: a prospective single center study. Am J Gastroenterol 2012;107:411-7. [Crossref] [PubMed]
  19. Rösch T, Repici A, Boeckxstaens G. Will reflux kill POEM? Endoscopy 2017;49:625-8. [Crossref] [PubMed]
  20. Akintoye E, Kumar N, Obaitan I, et al. Peroral endoscopic myotomy: a meta-analysis. Endoscopy 2016;48:1059-68. [Crossref] [PubMed]
  21. Inoue H, Sato H, Ikeda H, et al. Per-Oral Endoscopic Myotomy: A Series of 500 Patients. J Am Coll Surg 2015;221:256-64. [Crossref] [PubMed]
  22. Ramchandani M, Nageshwar Reddy D, Darisetty S, et al. Peroral endoscopic myotomy for achalasia cardia: Treatment analysis and follow up of over 200 consecutive patients at a single center. Dig Endosc 2016;28:19-26. [Crossref] [PubMed]
  23. Familiari P, Greco S, Gigante G, et al. Gastroesophageal reflux disease after peroral endoscopic myotomy: Analysis of clinical, procedural and functional factors, associated with gastroesophageal reflux disease and esophagitis. Dig Endosc 2016;28:33-41. [Crossref] [PubMed]
  24. Li QL, Chen WF, Zhou PH, et al. Peroral endoscopic myotomy for the treatment of achalasia: a clinical comparative study of endoscopic full-thickness and circular muscle myotomy. J Am Coll Surg 2013;217:442-51. [Crossref] [PubMed]
  25. Nabi Z, Ramchandani M, Chavan R, et al. Per-oral endoscopic myotomy for achalasia cardia: outcomes in over 400 consecutive patients. Endosc Int Open 2017;5:E331-9. [Crossref] [PubMed]
  26. Werner YB, Costamagna G, Swanström LL, et al. Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2 years. Gut 2016;65:899-906. [Crossref] [PubMed]
  27. Sharata AM, Dunst CM, Pescarus R, et al. Peroral endoscopic myotomy (POEM) for esophageal primary motility disorders: analysis of 100 consecutive patients. J Gastrointest Surg 2015;19:161-70; discussion 170. [Crossref] [PubMed]
  28. Tang X, Gong W, Deng Z, et al. Comparison of conventional versus Hybrid knife peroral endoscopic myotomy methods for esophageal achalasia: a case-control study. Scand J Gastroenterol 2016;51:494-500. [Crossref] [PubMed]
  29. Von Renteln D, Fuchs KH, Fockens P, et al. Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study. Gastroenterology 2013;145:309-11.e1-3.
  30. Cai MY, Zhou PH, Yao LQ, et al. Peroral endoscopic myotomy for idiopathic achalasia: randomized comparison of water-jet assisted versus conventional dissection technique. Surg Endosc 2014;28:1158-65. [Crossref] [PubMed]
  31. Shiwaku H, Inoue H, Sasaki T, et al. A prospective analysis of GERD after POEM on anterior myotomy. Surg Endosc 2016;30:2496-504. [Crossref] [PubMed]
  32. Sharma P, Wani S, Romero Y, et al. Racial and geographic issues in gastroesophageal reflux disease. Am J Gastroenterol 2008;103:2669-80. [Crossref] [PubMed]
  33. Jones EL, Meara MP, Schwartz JS, et al. Gastroesophageal reflux symptoms do not correlate with objective pH testing after peroral endoscopic myotomy. Surg Endosc 2016;30:947-52. [Crossref] [PubMed]
  34. Teitelbaum EN, Soper NJ, Santos BF, et al. Symptomatic and physiologic outcomes one year after peroral esophageal myotomy (POEM) for treatment of achalasia. Surg Endosc 2014;28:3359-65. [Crossref] [PubMed]
  35. Wang XH, Tan YY, Zhu HY, et al. Full-thickness myotomy is associated with higher rate of postoperative gastroesophageal reflux disease. World J Gastroenterol 2016;22:9419-26. [Crossref] [PubMed]
  36. Worrell SG, Alicuben ET, Boys J, et al. Peroral endoscopic myotomy for achalasia in a thoracic surgical practice. Ann Thorac Surg 2016;101:218-24; discussion 224. [Crossref] [PubMed]
  37. Schneider AM, Louie BE, Warren HF, et al. A matched comparison of per oral endoscopic myotomy to laparoscopic heller myotomy in the treatment of achalasia. J Gastrointest Surg 2016;20:1789-96. [Crossref] [PubMed]
  38. Khashab MA, El Zein M, Kumbhari V, et al. Comprehensive analysis of efficacy and safety of peroral endoscopic myotomy performed by a gastroenterologist in the endoscopy unit: a single-center experience. Gastrointest Endosc 2016;83:117-25. [Crossref] [PubMed]
  39. Kumbhari V, Familiari P, Bjerregaard NC, et al. Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case-control study. Endoscopy 2017;49:634-42. [Crossref] [PubMed]
  40. Bhayani NH, Kurian AA, Dunst CM, et al. A comparative study on comprehensive, objective outcomes of laparoscopic Heller myotomy with per-oral endoscopic myotomy (POEM) for achalasia. Ann Surg 2014;259:1098-103. [Crossref] [PubMed]
  41. Filicori F, Dunst CM, Sharata A, et al. Long-term outcomes following POEM for non-achalasia motility disorders of the esophagus. Surg Endosc 2018. [Epub ahead of print]. [Crossref] [PubMed]
  42. Chan SM, Wu JC, Teoh AY, et al. Comparison of early outcomes and quality of life after laparoscopic Heller's cardiomyotomy to peroral endoscopic myotomy for treatment of achalasia. Dig Endosc 2016;28:27-32. [Crossref] [PubMed]
  43. Rawlings A, Soper NJ, Oelschlager B, et al. Laparoscopic Dor versus Toupet fundoplication following Heller myotomy for achalasia: results of a multicenter, prospective, randomized-controlled trial. Surg Endosc 2012;26:18-26. [Crossref] [PubMed]
  44. Boeckxstaens GE, Annese V, des Varannes SB, et al. Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med 2011;364:1807-16. [Crossref] [PubMed]
  45. Khajanchee YS, Kanneganti S, Leatherwood AE, et al. Laparoscopic Heller myotomy with Toupet fundoplication: outcomes predictors in 121 consecutive patients. Arch Surg 2005;140:827-33; discussion 833-4. [Crossref] [PubMed]
  46. Zhang Y, Wang H, Chen X, et al. Per-Oral Endoscopic Myotomy Versus Laparoscopic Heller Myotomy for Achalasia: A Meta-Analysis of Nonrandomized Comparative Studies. Medicine 2016;95:e2736. [Crossref] [PubMed]
  47. Repici A, Fuccio L, Maselli R, et al. GERD after per-oral endoscopic myotomy as compared with Heller’s myotomy with fundoplication: a systematic review with meta-analysis. Gastrointest Endosc 2018;87:934-943.e18. [Crossref] [PubMed]
  48. Leeuwenburgh I, Scholten P, Caljé TJ, et al. Barrett’s esophagus and esophageal adenocarcinoma are common after treatment for achalasia. Dig Dis Sci 2013;58:244-52. [Crossref] [PubMed]
  49. Ujiki MB, Yetasook AK, Zapf M, et al. Peroral endoscopic myotomy: A short-term comparison with the standard laparoscopic approach. Surgery 2013;154:893-7; discussion 897. [Crossref] [PubMed]
  50. Chiu PW, Wu JC, Teoh AY, et al. Peroral endoscopic myotomy for treatment of achalasia: from bench to bedside (with video). Gastrointest Endosc 2013;77:29-38. [Crossref] [PubMed]
  51. Liu XJ, Tan YY, Yang RQ, et al. The Outcomes and Quality of Life of Patients with Achalasia after Peroral Endoscopic Myotomy in the Short-Term. Ann Thorac Cardiovasc Surg 2015;21:507-12. [Crossref] [PubMed]
  52. Swanstrom LL, Kurian A, Dunst CM, et al. Long-term outcomes of an endoscopic myotomy for achalasia: the POEM procedure. Ann Surg 2012;256:659-67. [Crossref] [PubMed]
  53. Verlaan T, Rohof WO, Bredenoord AJ, et al. Effect of peroral endoscopic myotomy on esophagogastric junction physiology in patients with achalasia. Gastrointest Endosc 2013;78:39-44. [Crossref] [PubMed]
  54. Minami H, Isomoto H, Yamaguchi N, et al. Peroral endoscopic myotomy for esophageal achalasia: clinical impact of 28 cases. Dig Endosc 2014;26:43-51. [Crossref] [PubMed]
  55. Hess MW, Hoenderop JG, Bindels RJ, et al. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther 2012;36:405-13. [Crossref] [PubMed]
  56. Giuliano C, Wilhelm SM, Kale-Pradhan PB. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev Clin Pharmacol 2012;5:337-44. [Crossref] [PubMed]
  57. Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol 2007;102:2047-56. [Crossref] [PubMed]
  58. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med 2016;176:238-46. [Crossref] [PubMed]
  59. Schoenfeld AJ, Grady D. Adverse Effects Associated With Proton Pump Inhibitors. JAMA Intern Med 2016;176:172-4. [Crossref] [PubMed]
  60. Zak Y, Meireles OR, Rattner DW, et al. Laparoscopic Toupet fundoplication for GERD after POEM [Internet]. SAGES Abstract Archives. [cited 2018 Sep 30]. Available online: https://www.sages.org/meetings/annual-meeting/abstracts-archive/laparoscopic-toupet-fundoplication-for-gerd-after-poem/
  61. Hungness ES, Teitelbaum EN, Santos BF, et al. Comparison of perioperative outcomes between peroral esophageal myotomy (POEM) and laparoscopic Heller myotomy. J Gastrointest Surg 2013;17:228-35. [Crossref] [PubMed]
  62. Jain D, Singhal S. Transoral incisionless fundoplication for refractory gastroesophageal reflux disease: where do we stand? Clin Endosc 2016;49:147-56. [Crossref] [PubMed]
  63. Wendling MR, Melvin WS, Perry KA. Impact of transoral incisionless fundoplication (TIF) on subjective and objective GERD indices: a systematic review of the published literature. Surg Endosc 2013;27:3754-61. [Crossref] [PubMed]
  64. Tyberg A, Choi A, Gaidhane M, et al. Transoral incisional fundoplication for reflux after peroral endoscopic myotomy: a crucial addition to our arsenal. Endosc Int Open 2018;6:E549-52. [Crossref] [PubMed]
  65. Triadafilopoulos G, DiBaise JK, Nostrant TT, et al. The Stretta procedure for the treatment of GERD: 6 and 12 month follow-up of the U.S. open label trial. Gastrointest Endosc 2002;55:149-56. [Crossref] [PubMed]
  66. Fass R, Cahn F, Scotti DJ, et al. Systematic review and meta-analysis of controlled and prospective cohort efficacy studies of endoscopic radiofrequency for treatment of gastroesophageal reflux disease. Surg Endosc 2017;31:4865-82. [Crossref] [PubMed]
  67. Inoue H, Ito H, Ikeda H, et al. Anti-reflux mucosectomy for gastroesophageal reflux disease in the absence of hiatus hernia: a pilot study. Ann Gastroenterol 2014;27:346-51. [PubMed]
  68. Ciotola F, Ditaranto A, Bilder C, et al. Electrical stimulation to increase lower esophageal sphincter pressure after POEM. Surg Endosc 2015;29:230-5. [Crossref] [PubMed]
  69. Dobashi A, Wu SW, Deters JL, et al. Endoscopic magnet placement into subadventitial tunnels for augmenting the lower esophageal sphincter using submucosal endoscopy: ex vivo and in vivo study in a porcine model (with video). Gastrointest Endosc 2018. [Epub ahead of print]. [PubMed]
doi: 10.21037/jxym.2019.01.02
Cite this article as: Callahan ZM, Su B, Ujiki M. Management of reflux after peroral endoscopic myotomy. J Xiangya Med 2019;4:6.