MARKERS OF GASTROESOPHAGEAL REFLUX DISEASE IN THEORY AND PRACTICE


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The article discusses the current problems of gastroesophageal reflux disease (GERD), and the possibility of its diagnosis at the current stage. A review to find reliable specific and sensitive biomarkers of GERD, such as indicators of the synthesis or degradation of tight intercellular junctions, basal impendancemetry and a number of others is presented. The results of examination of patients with GERD who visited specialized Gastroenterology Center of Perm are provided. The features of clinical manifestation, results of endoscopic and histological examinations of the esophagus in patients of different ages and duration of the disease course are discussed. Our data allow to reach more differentiated and individual approach to the appointment of treatment regimens for GERD taking into account all the features.

Full Text

Restricted Access

About the authors

E. Yu Plotnikova

SBEIHPE KemSMU of RMH

Email: eka-pl@rambler.ru
MD, Head of the Course of Gastroenterology at the Department of Postgraduate Training of Primary Care Physicians and Emergency Care

L. G Vologzhanina

SBEI HPE PSMU n.a. Acad. E.A. Wagner of RMH

A. A Samsonov

SBEI HPE "Moscow State Medical Stomatological University n.a. A.I. Evdokimov" of RMH

O. A Samsonova

Specialized Gastroenterological Center, Perm

D. N Andreev

SBEI HPE "Moscow State Medical Stomatological University n.a. A.I. Evdokimov" of RMH

References

  1. Dent J., Brun J., Fendrick A., Fennerty M., Janssens J., Kahrilas P., Lauritsen K., Reynolds J., Shaw M., Talley N. An evidence-based apprisal of reflux disease management - the Genval Workshop. Report. Gut. 1999; 44(Suppl. 2): 1-16.
  2. Vakil N, van Zanten S.V., Kahrilas P., Dent J., Jones R.; the Global Consensus Group. Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am. J. Gastroenterol. 2006; 101: 1900-20.
  3. Fass R., Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut. 2009; 58: 295-309.
  4. Strimbu K., Tavel J. What are biomarkers? Curr. Opin. HIV. AIDS. 2010; 5: 463-66.
  5. iuindell L.R., Dent J., Bennett J.R., Blum A.L., Armstrong D., Galmiche J.P., Johnson F., Hongo M., Richter J.E., Spechler S.J., Tytgat G.N., Wallin L. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999; 45: 172-80.
  6. Sharma P., Dent J., Armstrong D., Bergman J.J., Gossner L., Hoshihara Y., Jankowski J.A., Junghard O., Lundell L., Tytgat G.N., Vieth M. The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & Mcriteria. Gastroenterology. 2006; 131: 1392-99.
  7. Kia L., Pandolfino J.E., Kahrilas P.J. Biomarkers of Reflux Disease. Clin. Gastroenterol. Hepatol. 2016; 14(6): 790-97.
  8. Fiocca R., Mastracci L., Riddell R., Takubo K., Vieth M., Yerian L., Sharma P., Fernström P., Ruth M. Development of consensus guidelines for the histologic recognition of microscopic esophagitis in patients with gastroesophageal reflux disease: the Esohisto project. Hum. Pathol. 2010; 41: 223-31.
  9. Yerian L., Fiocca R., Mastracci L.,Riddell R., Vieth M., Sharma P., Franzen S., Fernstrom P., Ruth M. Refinement and reproducibility of histologic criteria for the assessment of microscopic lesions in patients with gastroesophageal reflux disease: the Esohisto Project. Dig. Dis. Sci. 2011; 56: 2656-65.
  10. Kandulski A., Jechorek D., Caro C., Weigt J., Wex T., Mönkemüller K., Malfertheiner P. Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn. Aliment. Pharmacol. Ther. 2013; 38: 643-51.
  11. Mönkemüller K., Wex T., Kuester D., Fry L.C., Kandulski A., Kropf S., Roessner A., Malfertheiner P. Role of tight junction proteins in gastroesophageal reflux disease. BMC. Gastroenterol. 2012; 12: 128.
  12. Tan J.C., Cui W.X., Heng D., Lin L. ERK1/2 participates in regulating the expression and distribution of tight junction proteins in the process of reflux esophagitis. J. Dig. Dis. 2014; 15: 409-18.
  13. Weijenborg P.W., Smout A.J., Verseijden C., van Veen H.A.,Verheij J., de Jonge W.J., Bredenoord A.J. Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis. Am. J. Physiol. 2014; 307: 323-29.
  14. Pardon N., Vanheel H., Toth J., et al. Effect of the perfusion of acidic and weakly acidic solutions on mucosal integrity and expression of cell-to-cell adhesion proteins in humans. Neurogastroenterol. Motil. 2014; 26: 36-7.
  15. Oshima T., Koseki J., Chen X., Matsumoto T., Miwa H. Acid modulates the squamous epithelial barrier function by modulating the localization of claudins in the superficial layers. Lab. Invest. 2012; 92: 22-31.
  16. Björkman E.V., Edebo A., Oltean M., Casselbrant A. Esophageal barrier function and tight junction expression in healthy subjects and patients with gastroesophageal reflux disease: functionality of esophageal mucosa exposed to bile salt and trypsin in vitro. Scand. J. Gastroenterol. 2013; 48: 1118-26.
  17. Wex T., Mönkemüller K., Stahr A., Kuester D., Fry L.C., Völkel S., Kandulski A., Roessner A., Malfertheiner P. Gastro-oesophageal reflux disease is associated with up-regulation of desmosomal components in oesophageal mucosa. Histopathology. 2012; 60: 405-15.
  18. Jovov B., Que J., Tobey N.A., Djukic Z., Hogan B.L., Orlando R.C. Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease. Am. J. Gastroenterol. 2011; 106: 1039-47.
  19. Tobey N.A., Carson J.L., Alkiek R.A., Orlando R.C. Dilated intercellular spaces: a morphological feature of acid reflux-damaged human esophageal epithelium. Gastroenterology. 1996; 111: 1200-205.
  20. Tobey N.A., Hosseini S.S., Argote C.M., Dobrucali A.M., Awayda M.S., Orlando R.C. Dilated intercellular spaces and shunt permeability in nonerosive acid-damaged esophageal epithelium. Am. J. Gastroenterol. 2004; 99: 13-22.
  21. Solcia E., Villani L., Luiinetti O., Trespi E., Strada E., Tinelli C., Fiocca R. Altered intercellular glycoconjugates and dilated intercellular spaces of esophageal epithelium in reflux disease. Virchows Archiv. 2000; 436: 207-16.
  22. Arul P., Phansalkar M., Alexander T., Padhi S., Vinoth B. Endoscope versus microscope in the diagnosis of esophageal non-erosive reflux disease: a study of 71 cases. Malays. J. Pathol. 2014; 36: 181-88.
  23. Ravelli A.M., Villanacci V., Ruzzenenti N., Grigolato Р, Tobanelli P., Klersy C., Rindi G. Dilated intercellular spaces: a major morphological feature of esophagitis. J. Pediatr. Gastroenterol. Nutr. 2006; 42: 510-15.
  24. Savarino E., Zentilin P., Mastracci L., Dulbecco P., Marabotto E., Gemignani L., Bruzzone L., de Bortoli N., Frigo A.C., Fiocca R., Savarino V. Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn. J. Gastroenterol. 2013; 48: 473-82.
  25. Farré R., van Malenstein H., De Vos R., Geboes K., Depoortere I., Vanden Berghe P., Fornari F., Blondeau K., Mertens V., Tack J., Sifrim D. Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces. Gut. 2008; 57: 1366-74.
  26. Calabrese C., Fabbri A., Bortolotti M., Cenacchi G., Areni A., Scialpi C., Miglioli M., Di Febo G. Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro-oesophageal reflux disease with or without bile reflux. Aliment. Pharmacol. Ther. 2003; 18: 525-32.
  27. Xue Y., Zhou L.Y., Lin S.R. Dilated intercellular spaces in gastroesophageal reflux disease patients and the changes of intercellular spaces after omeprazole treatment. Chin. Med. J. 2008; 121: 1297-301.
  28. Calabrese C., Fabbri A., Bortolotti M., Cenacchi G., Carlo S., Zahlane D., Miglioli M., Di Febo G. Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux. World. J. Gastroenterol. 2005; 11: 1876-80.
  29. Caviglia R., Ribolsi M., Gentile M., Rabitti C., Emerenziani S., Guarino M.P, Petitti T., Cicala M. Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease. Aliment. Pharmacol. Ther. 2007; 25: 629-36.
  30. Farré R., De Vos R., Geboes K., Verbecke K., Vanden Berghe P., Depoortere I., Blondeau K., Tack J., Sifrim D. Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces. Gut. 2007; 56: 1191-97.
  31. Zhang D.H., Zhou L.Y., Dong X.Y., Cui R.L., Xue Y., Lin S.R. Factors influencing intercellular spaces in the rat esophageal epithelium. World. J. Gastroenterol. 2010; 16: 1063-69.
  32. Katzka D.A., Ravi K., Geno D.M., Smyrk T.C., Iyer PG, Alexander J.A., Mabary J.E., Camilleri M., Vaezi M.F. Endoscopic mucosal impedance measurements correlate with eosinophilia and dilation of intercellular spaces in patients with eosinophilic esophagitis. Clin. Gastroenterol. Hepatol. 2015; 13: 1242-48.
  33. Ravelli A.M., Villanacci V., Ruzzenenti N., Grigolato P., Tobanelli P., Klersy C., Rindi G. Dilated intercellular spaces: a major morphological feature of esophagitis. J. Pediatr. Gastroenterol. Nutr. 2006; 42: 510-15.
  34. Farr R., Fornari F., Blondeau K., Vieth M., DeVos R., Bisschops R., Mertens V., Pauwels A., Tack J., Sifrim D. Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus. Gut. 2010; 59: 164-69.
  35. Tadiparthi R.A., Bansal A., Wani S., Mathur S., Hall S.B., Rastogi A., Higbee A., Gaddam S., Sharma P. Dilated intercellular spaces and lymphocytes on biopsy relate to symptoms in erosive GERD but not NERD. Aliment. Pharmacol. Ther. 2011; 33: 1202-208.
  36. Abd El-Rehim D.M., Fath El-Bab H.K., Kamal E.M. Expression of proteinase-activated receptor-2 in the esophageal mucosa of gastroesophageal reflux disease patients: a histomorphologic and immunohistochemical study. Appl. Immunohistochem. Mol. Morphol. 2014; 23: 646-52.
  37. Kandulski A., Wex T., Mönkemüller K., Kuester D., Fry L.C., Roessner A., Malfertheiner P. Proteinase-activated receptor-2 in the pathogenesis of gastroesophageal reflux disease. Am. J. Gastroenterol. pathogenesis of gastroesophageal reflux disease. Am. J. Gastroenterol. 2010; 105: 1934-43.
  38. Bhat Y.M., Bielefeldt K. Capsaicin receptor (TRPV1) and nonerosive reflux disease. Eur. J. Gastroenterol. Hepatol. 2006; 18: 263-70.
  39. Miwa H., Takubo K., Shimatani T., Furuta T., Oshima T., Tanaka J., Aida J., Ito M., Kurosawa S., Joh T., Wada T., Habu Y., Watanabe Y., Hongo M., Chiba T., Kinoshita Y. Histology of symptomatic gastroesophageal reflux disease: is it predictive of response to proton pump inhibitors? J. Gastroenterol. Hepatol. 2013; 28: 479-87.
  40. Calabrese C., Marzano V., Urbani A., Lazzarini G., Valerii M.C., Liguori G., Di Molfetta S., Rizzello F., Gionchetti P., Campieri M., Spisni E. Distinct proteomic profiles characterise non-erosive from erosive reflux disease. Aliment. Pharmacol. Ther. 2011; 34: 982-93.
  41. Vaezi M.F. Role of impedance/pH monitoring in refractory gerd: let's be careful out there! Gastroenterology. 2007; 132: 1621-22.
  42. Sifrim D., Castell D., Dent J., Kahrilas P.J. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut. 2004; 53: 1024-31.
  43. Farré R., Blondeau K., Clement D., Vicario M., Cardozo L., Vieth M., Mertens V., Pauwels A., Silny J., Jimenez M., Tack J., Sifrim D. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut. 2011; 60: 885-92.
  44. Zhong C., Duan L., Wang K., Xu Z., Ge Y., Yang C., Han Y. Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease. J. Gastroenterol. 2013; 48: 601-10.
  45. Savarino E., de Bortoli N., Zentilin P., et al. Esophageal baseline impedance values correlate with presence and severity of microscopic esophagitis in patients with gastroesophageal reflux disease. Gastroenterology. 2014; 146(5): 4.
  46. Seo A.Y., Shin C.M., Kim N., Yoon H., Park Y.S., Lee D.H. Correlation between hypersensitivity induced by esophageal acid infusion and the baseline impedance level in patients with suspected gastroesophageal reflux. J. Gastroenterol. 2014; 50: 735-43.
  47. Kandulski A., Weigt J, Caro C., Jechorek D., Wex T., Malfertheiner P. Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn. Clin. Gastroenterol. Hepatol. 2015; 13: 1075-81.
  48. Martinucci I., de Bortoli N., Savarino E., Piaggi P., Bellini M., Antonelli A., Savarino V., Frazzoni M., Marchi S. Esophageal baseline impedance levels in patients with pathophysiological characteristics of functional heartburn. Neurogastroenterol. Motil. 2014; 26: 546-45.
  49. de Bortoli N., Martinucci I., Savarino E., Tutuian R., Frazzoni M., Piaggi P., Bertani L., Furnari M., Franchi R., Russo S., Bellini M., Savarino V., Marchi S. Association between baseline impedance values and response proton pump inhibitors in patients with heartburn. Clin. Gastroenterol. Hepatol. 2015; 13: 1082-88.
  50. Kessing B.F., Hemmink G.J., Bredenoord A.J., et al. Acid inhibition improves but does not normalize low esophageal baseline impedance in patients with refractory GERD symptoms despite PPI. Gastroenterology. 2011; 140: 248.
  51. Loots C.M., Wijnakker R., van Wijk M.P, Davidson G., Benninga M.A., Omari T.I. Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapy. Neurogastroenterol. Motil. 2012; 24: 758-62, 351-52.
  52. Rinsma N.F., Farré R., Bouvy N.D., Masclee A.A., Conchillo J.M. The effect of endoscopic fundoplication and proton pump inhibitors on baseline impedance and heartburn severity in GERD patients. Neurogastroenterol. Motil. 2015; 27: 220-28.
  53. Mauritz F.A., Rinsma N.F., Conchillo J.M., et al. Esophageal mucosal integrity recovers after laparoscopic fundoplication in children with gastroesophageal reflux disease. Gastroenterology. 2014; 146: 506.
  54. Ribolsi M., Emerenziani S., Borrelli O., Balestrieri P, Addarii M.C., Petitti T., Cicala M. Impedance baseline and reflux perception in responder and non-responder nonerosive reflux disease patients. Scand. J. Gastroenterol. 2012; 47: 1266-73.
  55. Woodland P., Aktar R., Mthunzi E., Lee C., Peiris M., Preston S.L., Blackshaw L.A., Sifrim D. Distinct afferent innervation patterns within the human proximal and distal esophageal mucosa. Am. J. Gastrointest. Liver. Physiol. 2015; 308: 525-31.
  56. Ribolsi M., Savarino E., De Bortoli N., Balestrieri P., Furnari M., Martinucci I., Casale M., Greco F., Salvinelli F., Savarino V., Marchi S., Cicala M. Reflux pattern and role of impedance-pH variables in predicting PPI response in patients with suspected GERD-related chronic cough. Aliment. Pharmacol. Ther. 2014; 40: 966-73.
  57. Pauwels A., Farre R., Blondeau K., et al. Evaluation of reflux parameters and esophageal mucosal integrity in patients with chronic cough. Neurogastroenterol. Motil. 2013; 25: 11.
  58. Lee H.J., Jeong W.J., Shin C.M., et al. Relevance of laryngoscopy, pH-impedance monitoring and esophageal hypomotility in patients with suspected laryngopharyngeal reflux symptoms. Neurogastroenterol. Motil. 2014; 26: 11-82.
  59. Choi K., Min Y.W., Min B.-H., et al. The impairment of proximal esophageal mucosal integrity may play a causative role in patients with noncardiac chest pain. Gastroenterology. 2014; 146: 887.
  60. Weijenborg P.W., Rohof W.O., Akkermans L.M., et al. Esophageal electrical tissue impedance spectroscopy can detect esophageal permeability changes in gastroesophageal reflux disease during upper endoscopy. Gastroenterology. 2012; 142: 166-67.
  61. Lundin P., Karpefors M., Carlsson K., Hansen M.B., Ruth M. Bioimpedance spectroscopy: a new tool to assess early esophageal changes linked to gastroesophageal reflux disease? Dis. Esoph. 2011; 24: 462-69.
  62. Manabe N., Kamada T., Kusunoki H., et al. Newly developed bioelectrical admittance measurement distinguishes patients with non-erosive reflux disease from those with functional heartburn. Gastroenterology. 2014; 146: 116.
  63. Saritas Yuksel E., Higginbotham T., Slaughter J.C., Mabary J., Kavitt R.T., Garrett C.G., Vaezi M.F. Use of direct, endoscopic-guided measurements of mucosal impedance in diagnosis of gastroesophageal reflux disease. Clin. Gastroenterol. Hepatol. 2012; 10: 1110-16.
  64. Kim H.P, Heller L.T., Ates F., et al. Intraluminal impedance versus mucosal impedance testing for the diagnosis of GERD: do they measure the same thing? Gastroenterology. 2015; 148: 615-16.
  65. Ates F.,Yuksel E.S.,Higginbotham T.,Slaughter J.C., Mabary J., Kavitt R.T., Garrett C.G., Francis D., Vaezi M.F. Mucosal impedance discriminates GERD from non-GERD conditions. Gastroenterology. 2015; 148: 334-43.
  66. Маев И.В., Самсонов А.А., Андреев Д.Н. Клиническое значение синдрома «перекреста» функциональной диспепсии и гастроэзофагеальной рефлюксной болезни. Клинические перспективы гастроэнтерол., гепатол. 2013; 5: 17-22.
  67. Маев И.В., Дичева Д.Т., Андреев Д.Н. Подходы к индивидуализации лечения гастроэзофагеальной рефлюксной болезни. Эффективная фармакотерапия. Гастроэнтерология. 2012; 4: 1-5.
  68. Андреев Д.Н., Кучерявый Ю.А. Перспективы лечения гастроэзофагеальной рефлюксной болезни. Consilium Medicum. Гастроэнтерология. 2013; 2: 9-14.
  69. Плотникова Е.Ю., Вологжанина Л.Г., Самсонов А.А., Андреев Д.Н., Самсонова О.А. Течение гастроэзофагеальной рефлюксной болезни по результатам ретроспективного 5-летнего наблюдения. Фарматека. 2016; 6: 64-9.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies