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Endoscopy 2022; 54(09): 839-847
DOI: 10.1055/a-1753-9801
Original article

Risk factors and long-term course of gastroesophageal reflux disease after peroral endoscopic myotomy: A large-scale multicenter cohort study in Japan

Hironari Shiwaku 
 1   Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan
,
Hiroki Sato 
 2   Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
 3   Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
,
Yuto Shimamura 
 4   Digestive Diseases Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan
,
Hirofumi Abe
 5   Department of Gastroenterology, Kobe University Hospital, Hyogo, Japan
,
Junya Shiota
 6   Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan
,
Chiaki Sato
 7   Division of Advanced Surgical Science and Technology, Tohoku University School of Medicine, Miyagi, Japan
,
Masaki Ominami
 8   Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
,
Hiroyuki Sakae 
 9   Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
,
Yoshitaka Hata 
10   Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
,
Hisashi Fukuda
11   Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi, Japan
,
Ryo Ogawa
12   Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
,
Jun Nakamura
13   Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
,
Tetsuya Tatsuta
14   Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Aomori, Japan
,
Yuichiro Ikebuchi
15   Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine Tottori University Faculty of Medicine, Tottori, Japan
,
Hiroshi Yokomichi
16   Department of Health Sciences, University of Yamanashi, Yamanashi, Japan
,
Suguru Hasegawa
 1   Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan
,
Haruhiro Inoue
 4   Digestive Diseases Center, Showa University Koto-Toyosu Hospital, Tokyo, Japan
› Author AffiliationsSupported by: JGA Clinical Research Grants, Multicenter Research Grant of The Japanese Foundation for Research and Promotion of Endoscopy 2021–1
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Correction: Risk factors and long-term course of gastroesophageal reflux disease after peroral endoscopic myotomy: A large-scale multicenter cohort study in JapanEndoscopy 2022; 54(09): C13-C13
DOI: 10.1055/a-1778-9730

Abstract

Background Gastroesophageal reflux disease (GERD) and reflux esophagitis remain problems after peroral endoscopic myotomy (POEM). This study aimed to elucidate the risk factors and long-term course of reflux esophagitis and symptomatic GERD after POEM.

Methods This multicenter cohort study involved 14 high volume centers. Overall, 2905 patients with achalasia-related esophageal motility disorders treated with POEM were analyzed for reflux esophagitis, severe reflux esophagitis (Los Angeles classification C or D), and symptomatic GERD.

Results Reflux esophagitis was diagnosed in 1886 patients (64.9 %). Age ≥ 65 years (risk ratio [RR] 0.85), male sex (RR 1.11), posterior myotomy (RR 1.12), esophageal myotomy > 10 cm (RR 1.12), and gastric myotomy > 2 cm (RR 1.17) were independently associated with reflux esophagitis. Severe reflux esophagitis was diagnosed in 219 patients (7.5 %). Age ≥ 65 years (RR 1.72), previous treatments (RR 2.21), Eckardt score ≥ 7 (RR 0.68), sigmoid-type achalasia (RR 1.40), and esophageal myotomy > 10 cm (RR 1.59) were factors associated with severe reflux esophagitis. Proton pump inhibitors (PPIs) were more effective for reflux esophagitis at 5-year follow-up (P = 0.03) than after 1 year (P = 0.08). Symptomatic GERD was present in 458 patients (15.9 %). Symptom duration ≥ 10 years (RR 1.28), achalasia diagnosis (RR 0.68), integrated relaxation pressure ≥ 26 (RR 0.60), and posterior myotomy (RR 0.80) were associated with symptomatic GERD. The incidence of symptomatic GERD was lower at 5-year follow-up compared with that after 1 year (P = 0.04), particularly in PPI users (P < 0.001).

Conclusions The incidence of severe reflux esophagitis was low after POEM, but excessive myotomy for older patients with previous treatments should be avoided. Early phase symptomatic GERD is non-acid reflux dependent and the natural course is favorable, basically supporting conservative treatment.

Tables 1 s–5 s, Figs. 1 s–3 s



Publication History

Received: 16 September 2021

Accepted after revision: 03 January 2022

Article published online:
16 February 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Inoue H, Minami H, Kobayashi Y. et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010; 42: 265-271
    Google Scholar
  • 2 Ponds FA, Fockens P, Lei A. et al. Effect of peroral endoscopic myotomy vs pneumatic dilation on symptom severity and treatment outcomes among treatment-naive patients with achalasia: a randomized clinical trial. JAMA 2019; 322: 134-144
    CrossrefPubMedGoogle Scholar
  • 3 Werner YB, Hakanson B, Martinek J. et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. NEJM 2019; 381: 2219-2229
    CrossrefPubMedGoogle Scholar
  • 4 Vaezi MF, Pandolfino JE, Yadlapati RH. et al. ACG Clinical Guidelines: Diagnosis and management of achalasia. Am J Gastroenterol 2020; 115: 1393-1411
    CrossrefPubMedGoogle Scholar
  • 5 Oude Nijhuis RAB, Zaninotto G, Roman S. et al. European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations. United European Gastroenterol J 2020; 8: 13-33
    Google Scholar
  • 6 Inoue H, Shiwaku H, Iwakiri K. et al. Clinical practice guidelines for peroral endoscopic myotomy. Dig Endosc 2018; 30: 563-579
    CrossrefPubMedGoogle Scholar
  • 7 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: 451-460
    CrossrefPubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 Shiwaku H, Inoue H, Sato H. et al. Peroral endoscopic myotomy for achalasia: a prospective multicenter study in Japan. Gastrointest Endosc 2020; 91: 1037-1044 e2
    CrossrefPubMedGoogle Scholar
  • 10 Nabi Z, Ramchandani M, Kotla R. et al. Gastroesophageal reflux disease after peroral endoscopic myotomy is unpredictable, but responsive to proton pump inhibitor therapy: a large, single-center study. Endoscopy 2020; 52: 643-651
    Google Scholar
  • 11 Kumbhari V, Familiari P, Bjerregaard NC. et al. Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case-control study. Endoscopy 2017; 49: 634-642
    Google Scholar
  • 12 Mota RCL, de Moura EGH, de Moura DTH. et al. Risk factors for gastroesophageal reflux after POEM for achalasia: a systematic review and meta-analysis. Surg Endosc 2021; 35: 383-397
    CrossrefPubMedGoogle Scholar
  • 13 Liu Z-Q, Li Q-L, Chen W-F. et al. The effect of prior treatment on clinical outcomes in patients with achalasia undergoing peroral endoscopic myotomy. Endoscopy 2019; 51: 307-316
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Iwakiri K, Kinoshita Y, Habu Y. et al. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015. J Gastroenterol 2016; 51: 751-767
    CrossrefPubMedGoogle Scholar
  • 15 Sato H, Yokomichi H, Takahashi K. et al. Epidemiological analysis of achalasia in Japan using a large-scale claims database. J Gastroenterol 2019; 54: 621-627
    CrossrefPubMedGoogle Scholar
  • 16 Shrier I, Platt RW. Reducing bias through directed acyclic graphs. BMC Med Res Methodol 2008; 8: 70
    CrossrefPubMedGoogle Scholar
  • 17 Eckardt VF. Clinical presentations and complications of achalasia. Gastrointest Endosc Clin N Am 2001; 11: 281-292, vi
    CrossrefPubMedGoogle Scholar
  • 18 Kahrilas PJ, Bredenoord AJ, Fox M. et al. The Chicago Classification of esophageal motility disorders, v3. 0. Neurogastroenterol Motil 2015; 27: 160-174
    CrossrefPubMedGoogle Scholar
  • 19 Kuribayashi S, Iwakiri K, Kawada A. et al. Variant parameter values-as defined by the Chicago Criteria-produced by ManoScan and a new system with Unisensor catheter. Neurogastroenterol Motil 2015; 27: 188-194
    CrossrefPubMedGoogle Scholar
  • 20 Song BG, Min YW, Lee H. et al. Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system. Neurogastroenterol Motil 2018; DOI: 10.1111/nmo.13221.
    CrossrefPubMedGoogle Scholar
  • 21 do Carmo GC, Jafari J, Sifrim D. et al. Normal esophageal pressure topography metrics for data derived from the Sandhill-Unisensor high-resolution manometry assembly in supine and sitting positions. Neurogastroenterol Motil 2015; 27: 285-292
    CrossrefPubMedGoogle Scholar
  • 22 Japan Esophageal Society. Descriptive rules for achalasia of the esophagus, June 2012: 4th Edition. Esophagus 2017; 14: 275-289
    CrossrefPubMedGoogle Scholar
  • 23 Lundell LR, Dent J, Bennett JR. et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999; 45: 172-180
    CrossrefPubMedGoogle Scholar
  • 24 Jones R, Junghard O, Dent J. et al. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther 2009; 30: 1030-1038
    CrossrefPubMedGoogle Scholar
  • 25 Westreich D, Greenland S. The table 2 fallacy: Presenting and interpreting confounder and modifier coefficients. Am J Epidemiol 2013; 177: 292-298
    CrossrefPubMedGoogle Scholar
  • 26 Sato H, Sagara S, Suzuki K. et al. Assessments of histologic changes after peroral endoscopic myotomy. Gastrointest Endosc 2016; 84: 377-378
    CrossrefPubMedGoogle Scholar
  • 27 Ishimura N, Owada Y, Aimi M. et al. No increase in gastric acid secretion in healthy Japanese over the past two decades. J Gastroenterol 2015; 50: 844-852
    CrossrefPubMedGoogle Scholar
  • 28 Iijima K, Koike T, Abe Y. et al. Time series analysis of gastric acid secretion over a 20-year period in normal Japanese men. J Gastroenterol 2015; 50: 853-861
    CrossrefPubMedGoogle Scholar
  • 29 Martino F, Perestrelo AR, Vinarský V. et al. Cellular mechanotransduction: from tension to function. Front Physiol 2018; 9: 824
    CrossrefPubMedGoogle Scholar
  • 30 Fujimoto K. Review article: prevalence and epidemiology of gastro-oesophageal reflux disease in Japan. Aliment Pharmacol Ther 2004; 20: 5-8
    CrossrefPubMedGoogle Scholar
  • 31 Furukawa N, Iwakiri R, Koyama T. et al. Proportion of reflux esophagitis in 6010 Japanese adults: prospective evaluation by endoscopy. J Gastroenterol 1999; 34: 441-444
    CrossrefPubMedGoogle Scholar
  • 32 Kamal F, Ismail MK, Khan MA. et al. Efficacy and safety of peroral endoscopic myotomy in the management of recurrent achalasia after failed Heller myotomy: a systematic review and meta-analysis. Ann Gastroenterol Hepatol 2021; 34: 155-163
    PubMedGoogle Scholar
  • 33 Ponds FA, Oors JM, Smout AJPM. et al. Reflux symptoms and oesophageal acidification in treated achalasia patients are often not reflux related. Gut 2021; 70: 30-39
    CrossrefPubMedGoogle Scholar
  • 34 Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013; 108: 308-328; quiz 329
    CrossrefPubMedGoogle Scholar
  • 35 Dirac MA, Safiri S, Tsoi D. et al. The global, regional, and national burden of gastro-oesophageal reflux disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020; 5: 561-581
    CrossrefPubMedGoogle Scholar