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Non-acid reflux and esophageal dysmotility is associated with early esophageal squamous cell carcinoma

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Abstract

Background

Studies have demonstrated that non-acid reflux (NAR) is associated with esophageal squamous cell carcinoma (ESCC). Esophageal dysmotility is associated with NAR but few studies have focused on the esophageal motility of ESCC patients. We explored the relationship between ESCC, NAR and esophageal dysmotility with the aid of multichannel intraluminal impedance and pH (MII-pH) and high-resolution manometry (HRM).

Methods

From Jan 2021 to Oct 2022, 20 patients with superficial ESCC were enrolled as the ESCC group, while 20 age and gender matched individuals without gastroesophageal reflux disease (GERD) symptoms and 20 age and gender matched patients with GERD symptoms were recruited as the control groups. Patients received 24 h MII-pH and HRM procedure before endoscopic submucosal dissection (ESD), and the data were then collected to identify the type of reflux and esophageal dysmotility.

Results

Prevalence of esophageal dysmotility was significantly different among the three groups, 75.0% in the ESCC group, 35.0% in the non-GERD group and 70.0% in the GERD group (P = 0.029). NAR episodes at 15 cm above the lower esophageal sphincter (LES) in the ESCC group were significantly higher than that in the non-GERD group (6.5 (3.5–9.3) vs 1.0 (0.8–4.0), P = 0.001) and were similar with that in the GERD group (6.5 (3.5–9.3) vs 5.5 (3.0–10.5), P > 0.05). NAR episodes at 5 cm above LES was significantly higher in the ESCC group than that in the non-GERD group (38.0 (27.0–60.0) vs 18.0 (11.8–25.8), P = 0.001) and was significantly higher than that in the GERD group (38.0 (27.0–60.0) vs 20.0 (9.8–30.5)), P = 0.010). Prevalence of pathologic non-acid reflux was significantly different among the three groups, 30.0% in the ESCC group, 0.0% in the non-GERD group and 10.0% in the GERD group (P < 0.001).

Conclusion

Our study found NAR and esophageal dysfunction frequently occur in ESCC patients. NAR and esophageal dysmotility may be associated with ESCC.

Clinical trial registration number

ChiCTR2200061456.

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Data availability

All data included in this study are available upon request by contact with the corresponding author.

References

  • Banki F et al (2005) Barrett’s esophagus in females: a comparative analysis of risk factors in females and males. Am J Gastroenterol 100(3):560–567

    Article  PubMed  Google Scholar 

  • Brandt MG, Darling GE, Miller L (2004) Symptoms, acid exposure and motility in patients with Barrett’s esophagus. Can J Surg 47(1):47–51

    PubMed  PubMed Central  Google Scholar 

  • Cook MB et al (2010) Serum pepsinogens and Helicobacter pylori in relation to the risk of esophageal squamous cell carcinoma in the alpha-tocopherol, beta-carotene cancer prevention study. Cancer Epidemiol Biomarkers Prev 19(8):1966–1975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Vries AC et al (2009) Increased risk of esophageal squamous cell carcinoma in patients with gastric atrophy: independent of the severity of atrophic changes. Int J Cancer 124(9):2135–2138

    Article  PubMed  Google Scholar 

  • Endoscopic Classification Review Group (2005) Update on the Paris classification of superficial neoplastic lesions in the digestive tract. Endoscopy 37(6):570–578

    Article  Google Scholar 

  • Freedman ND et al (2007) A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol 165(12):1424–1433

    Article  PubMed  Google Scholar 

  • Furuta GT, Katzka DA (2015) Eosinophilic esophagitis. N Engl J Med 373(17):1640–1648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gyawali CP et al (2018) Modern diagnosis of GERD: the Lyon consensus. Gut 67(7):1351–1362

    Article  PubMed  Google Scholar 

  • Hachem C, Shaheen NJ (2016) Diagnosis and management of functional heartburn. Am J Gastroenterol 111(1):53–61

    Article  PubMed  Google Scholar 

  • Herregods TV, Bredenoord AJ, Smout AJ (2015) Pathophysiology of gastroesophageal reflux disease: new understanding in a new era. Neurogastroenterol Motil 27(9):1202–1213

    Article  CAS  PubMed  Google Scholar 

  • Iijima K et al (2010) Gastric hyposecretion in esophageal squamous-cell carcinomas. Dig Dis Sci 55(5):1349–1355

    Article  CAS  PubMed  Google Scholar 

  • Kgomo M, Mokoena TR, Ker JA (2017) Non-acid gastro-oesophageal reflux is associated with squamous cell carcinoma of the oesophagus. BMJ Open Gastroenterol 4(1):e000180

    Article  PubMed  PubMed Central  Google Scholar 

  • Lagergren J et al (1999) Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340(11):825–831

    Article  CAS  PubMed  Google Scholar 

  • Lagergren J et al (2017) Oesophageal cancer. Lancet 390(10110):2383–2396

    Article  PubMed  Google Scholar 

  • Lee TY et al (2008) Barrett’s esophagus and severe reflux esophagitis share common pathophysiological characteristics among Chinese in Taiwan. Intern Med 47(20):1767–1773

    Article  PubMed  Google Scholar 

  • Lord RV et al (2009) Hiatal hernia, lower esophageal sphincter incompetence, and effectiveness of Nissen fundoplication in the spectrum of gastroesophageal reflux disease. J Gastrointest Surg 13(4):602–610

    Article  PubMed  Google Scholar 

  • Oikawa T et al (2010) Deficient aldehyde dehydrogenase 2 is associated with increased risk for esophageal squamous cell carcinoma in the presence of gastric hypochlorhydria. Scand J Gastroenterol 45(11):1338–1344

    Article  CAS  PubMed  Google Scholar 

  • Porter RF et al (2012) Fragmented esophageal smooth muscle contraction segments on high resolution manometry: a marker of esophageal hypomotility. Neurogastroenterol Motil 24(8):763-e353

    Article  CAS  PubMed  Google Scholar 

  • Reddy CA et al (2019) High-resolution manometry diagnosis of ineffective esophageal motility is associated with higher reflux burden. Dig Dis Sci 64(8):2199–2205

    Article  PubMed  Google Scholar 

  • Roman S et al (2017) Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: update of the Porto consensus and recommendations from an international consensus group. Neurogastroenterol Motil 29(10):1–15

    Article  CAS  PubMed  Google Scholar 

  • Savarino E et al (2011) Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 34(4):476–486

    Article  CAS  PubMed  Google Scholar 

  • Savarino E, Giacchino M, Savarino V (2013) Dysmotility and reflux disease. Curr Opin Otolaryngol Head Neck Surg 21(6):548–556

    PubMed  Google Scholar 

  • Segawa K et al (1988) Chronic alcohol abuse leads to gastric atrophy and decreased gastric secretory capacity: a histological and physiological study. Am J Gastroenterol 83(4):373–379

    CAS  PubMed  Google Scholar 

  • Soroush A, Etemadi A, Abrams JA (2022) Non-acid fluid exposure and esophageal squamous cell carcinoma. Dig Dis Sci 67(7):2754–2762

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K et al (2017) Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study. Dis Esophagus 30(11):1–8

    Article  CAS  PubMed  Google Scholar 

  • Takeda T et al (2018) Effect of esophageal endoscopic submucosal dissection on motility and symptoms: a prospective study. Gastroenterol Res Pract 2018:3735473

    Article  PubMed  PubMed Central  Google Scholar 

  • Triadafilopoulos G et al (2016) Clinical and pH study characteristics in reflux patients with and without ineffective oesophageal motility (IEM). BMJ Open Gastroenterol 3(1):e000126

    Article  PubMed  PubMed Central  Google Scholar 

  • Uno K et al (2011) Direct measurement of gastroesophageal reflux episodes in patients with squamous cell carcinoma by 24-h pH-impedance monitoring. Am J Gastroenterol 106(11):1923–1929

    Article  CAS  PubMed  Google Scholar 

  • Wild CP et al (2020) World cancer report: cancer research for cancer prevention. International Agency for Research on Cancer, Lyon. http://publications.iarc.fr/586

    Google Scholar 

  • Yadlapati R et al (2021) Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0©. Neurogastroenterol Motil 33(1):e14058

    Article  PubMed  PubMed Central  Google Scholar 

  • Yokoyama A et al (2009) Chronic atrophic gastritis and metachronous gastric cancer in Japanese alcoholic men with esophageal squamous cell carcinoma. Alcohol Clin Exp Res 33(5):898–905

    Article  CAS  PubMed  Google Scholar 

  • Zerbib F et al (2006) Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy. Am J Gastroenterol 101(9):1956–1963

    Article  PubMed  Google Scholar 

  • Zerbib F et al (2020) Ineffective esophageal motility and bolus clearance. A study with combined high-resolution manometry and impedance in asymptomatic controls and patients. Neurogastroenterol Motil 32(9):e13876

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported in part by the National Natural Science Foundation of China (NSFC) under Grants 82100567and 81770540, in part by the Key Research and Development Projects of Shaanxi Province under Grants 2021sf-135.

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    Authors and Affiliations

    1. Department of Gastroenterology, Second Affiliated Hospital, **’an Jiaotong University, **’an, 710004, China

      Yujie Hao, **aosa Jiang, Yueqin Zheng, Qiuju Ran, **aoyu Xu, Baicang Zou, **hai Wang, Na Liu & Bin Qin

    2. Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nan**g University, Nan**g, 210008, China

      Mo Wang

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    1. Yujie Hao
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    Contributions

    Design: JW, NL, and BQ. Conception: BQ, BZ, and YH. Data extraction: YH and XX. Data analysis and drafting of the manuscript: YH, MW and YZ. Statistical analysis: YH, XJ, and QR.

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    Correspondence to **hai Wang, Na Liu or Bin Qin.

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    Yujie Hao and Mo Wang are equally contributed to this work.

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    Hao, Y., Wang, M., Jiang, X. et al. Non-acid reflux and esophageal dysmotility is associated with early esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 149, 8327–8334 (2023). https://doi.org/10.1007/s00432-023-04772-5

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