fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2020-5-1-93-100fcmedicine-268Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESСовременные аспекты ведения пациентов с рефрактерной гастроэзофагеальной рефлюксной болезньюCurrent management of proton pump inhibitor-refractory gastroesophageal reflux diseasehttps://orcid.org/0000-0002-9980-2294ЦукановВ. В.TsukanovV. V.

Цуканов Владислав Владимирович - доктор медицинских наук, профессор, заведующий клиническим отделением патологии пищеварительной системы у взрослых и детей.

660022, Россия, г. Красноярск, ул. Партизана Железняка, 3г

Prof. Vladislav V. Tsukanov - MD, DSc, Professor, Head of the Unit for Digestive Diseases.

3G, Partizana Zheleznyaka Street, Krasnoyarsk, 660022, Russian Federation

gastro@impn.ruhttps://orcid.org/0000-0002-6481-3196ВасютинА. В.VasyutinA. V.

Васютин Александр Викторович - кандидат медицинских наук, старший научный сотрудник клинического отделения патологии пищеварительной системы у взрослых и детей.

660022, Россия, г. Красноярск, ул. Партизана Железняка, 3г

Dr. Aleksandеr V. Vasyutin - MD, PhD, Senior Researcher, Unit for Digestive Diseases.

3G, Partizana Zheleznyaka Street, Krasnoyarsk, 660022, Russian Federation

https://orcid.org/0000-0001-7518-1895ТонкихЮ. Л.TonkikhYu. L.

Тонких Юлия Леонгардовна - кандидат медицинских наук, ведущий научный сотрудник клинического отделения патологии пищеварительной системы у взрослых и детей.

660022, Россия, г. Красноярск, ул. Партизана Железняка, 3г

Dr. Yulia L. Tonkikh - MD, PhD, Leading Researcher, Unit for Digestive Diseases.

3G, Partizana Zheleznyaka Street, Krasnoyarsk, 660022, Russian Federation

ФГБНУ «Федеральный исследовательский центр «Красноярский научный центр Сибирского отделения Российской академии наук» (ФИЦ КНЦ СО РАН), обособленное подразделение «Научно-исследовательский институт медицинских проблем Севера» (НИИ МПС)РоссияResearch Institute for Medical Problems in the North, Krasnoyarsk Research Center, Siberian Branch of the Russian Academy of SciencesRussian Federation2020270620205293100Copyright © Цуканов В.В., Васютин А.В., Тонких Ю.Л., 20202020Цуканов В.В., Васютин А.В., Тонких Ю.Л.Tsukanov V.V., Vasyutin A.V., Tonkikh Y.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/268

Выполнен обзор литературы, посвященный современным представлениям о диагностике и лечении рефрактерной к ингибиторам протонной помпы (ИПП) гастроэзофагеальной рефлюксной болезни (ГЭРБ). К рефрактерной ГЭРБ относят недостаточный ответ на назначение два раза в сутки ИПП в течение 8 недель терапии при наличии патологического гастроэзофагеального рефлюкса. У лиц с рефрактерной ГЭРБ часто наблюдается некислый рефлюкс в пищевод и отсутствие связи симптомов с эпизодами рефлюкса. В развитых странах частота рефрактерной ГЭРБ составляет 30-40% от общего количества пациентов, получающих ИПП. Для диагностики рефрактерной ГЭРБ применяют внимательный анализ симптомов, эзофагогастроскопию с морфологическим исследованием и рН-импедансометрию, позволяющую установить связь симптомов с эпизодами рефлюкса. Важным вопросом является дифференциальная диагностика функциональной изжоги, гиперчувствительности пищевода к рефлюксу и неэрозивной рефлюксной болезни. По результатам рН-импедансометрии для функциональной изжоги характерно нормальное время с рН ниже 4 в пищеводе и отсутствие связи эпизодов рефлюкса с симптомами ГЭРБ. Гиперчувствительность пищевода к рефлюксу диагностируется при нормальной кислотной экспозиции в пищеводе и наличии связи эпи- зодов рефлюкса с симптомами ГЭРБ. Для верификации диагноза неэрозивной рефлюксной болезни достаточно регистрации патологической кислотной экспозиции в пищеводе (общее время с рН в пищеводе ниже 4 больше 6%). Лечение включает модификацию диеты и образа жизни для снижения веса у больных с ожирением, оптимизацию назначения ИПП, при необходимости применение альгината, прокинетиков, баклофена и других препаратов. Хирургические методы лечения при наличии показаний и квалифицированного обследования широко применяются и дают хорошие результаты.

Here we review current concepts in diagnosis and treatment of proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (PPIGERD) which includes an insufficient response to daily PPI 8-week therapy in combination with pathological gastroesophageal reflux. Patients with PPI-GERD frequently suffer from non-acidic and asymptomatic gastroesophageal reflux. In developed countries, PPI-GERD accounts for 30-40% of all patients receiving PPIs. Diagnosis of PPIGERD is performed by means of clinical anamnesis, esophagogastroscopy and impedance-pH monitoring. PPI-GERD needs to be differentiated with functional heartburn, reflux hypersensitivity and nonerosive reflux disease. Functional heartburn is characterised by reference time with a esophageal pH < 4 and the absence of a link between reflux episodes and GERD symptoms. Reflux hypersensitivity is diagnosed with normal esophageal acid exposure and association of reflux episodes with symptoms of GERD. Nonerosive reflux disease can be diagnosed solely by evaluating pathological acid exposure (pH < 4 for > 6% of the time). Treatment of PPI-GERD includes diet and lifestyle modification to reduce weight in obese patients, optimization of PPI use, and administration of alginate, prokinetics, baclofen and other drugs. Surgical treatment is also widely used and provide good results.

гастроэзофагеальная рефлюксная болезньдиагностикалечениеингибиторы протонной помпыgastroesophageal reflux diseasediagnosistreatmentproton pump inhibitorsReferencesVakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900-1920. https://doi.org/10.1111/j.1572-0241.2006.00630.xVakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900-1920. https://doi.org/10.1111/j.1572-0241.2006.00630.xБуторин Н.Н., Бичурина Т.Б., Цуканов В.В., Каспаров Э.В., Куклин Д.В., Тимошенко В.О., Штыгашева О.В., Маады А.С., Васютин А.В. Распространенность и клинические аспекты пищевода Барретта у населения Восточной Сибири. Терапевтический архив. 2013;85(1):62-65Butorin NN, Bichurina TB, Tsukanov VV, Kasparov EV, Kuklin DV, Timoshenko VO, Shtygasheva OV, Maady AS, Vasiutin AV. The prevalence and clinical aspects of Barrett's esophagus in the population of Eastern Siberia. Therapeutic Archive. 2013;85(1):62-65. (In Russ.)El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014;63(6):871-880. https://doi.org/10.1136/gutjnl-2012-304269El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014;63(6):871-880. https://doi.org/10.1136/gutjnl-2012-304269Peery AF, Crockett SD, Murphy CC, Lund JL, Dellon ES, Williams JL, Jensen ET, Shaheen NJ, Barritt AS, Lieber SR, Kochar B, Barnes EL, Fan YC, Pate V, Galanko J, Baron TH, Sandler RS. Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018. Gastroenterology. 2019;156(1):254-272. https://doi.org/10.1053/j.gastro.2018.08.063Peery AF, Crockett SD, Murphy CC, Lund JL, Dellon ES, Williams JL, Jensen ET, Shaheen NJ, Barritt AS, Lieber SR, Kochar B, Barnes EL, Fan YC, Pate V, Galanko J, Baron TH, Sandler RS. Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018. Gastroenterology. 2019;156(1):254-272. https://doi.org/10.1053/j.gastro.2018.08.063Gyawali CP, Fass R. Management of Gastroesophageal Reflux Disease. Gastroenterology. 2018;154(2):302-318. https://doi.org/10.1053/j.gastro.2017.07.049Gyawali CP, Fass R. Management of Gastroesophageal Reflux Disease. Gastroenterology. 2018;154(2):302-318. https://doi.org/10.1053/j.gastro.2017.07.049El-Serag H, Becher A, Jones R. Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies. Aliment Pharmacol Ther. 2010;32(6):720-737. https://doi.org/10.1111/j.1365-2036.2010.04406.xEl-Serag H, Becher A, Jones R. Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies. Aliment Pharmacol Ther. 2010;32(6):720-737. https://doi.org/10.1111/j.1365-2036.2010.04406.xЦуканов В.В., Онучина Е.В., Васютин А.В., Буторин Н.Н., Амельчугова О.С. Клинические аспекты гастроэзофагеальной рефлюксной болезни у лиц пожилого возраста: результаты 5-летнего проспективного исследования. Терапевтический архив. 2014;86(2):23-26Tsukanov VV, Onuchina EV, Vasyutin AV, Butorin NN, Amelchugova OS. Clinical aspects of gastroesophageal reflux disease in elderly patients: results of a 5-year prospective study. Therapeutic Archive. 2014;86(2):23-26. (In Russ.).Yadlapati R, DeLay K. PPI Refractory Gastroesophageal Reflux Disease. Med Clin North Am. 2019;103(1):15-27. https://doi.org/10.1016/j.mcna.2018.08.002Yadlapati R, DeLay K. PPI Refractory Gastroesophageal Reflux Disease. Med Clin North Am. 2019;103(1):15-27. https://doi.org/10.1016/j.mcna.2018.08.002Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut. 2012;61(9):1340-1354. https://doi.org/10.1136/gutjnl-2011-301897Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut. 2012;61(9):1340-1354. https://doi.org/10.1136/gutjnl-2011-301897Hershcovici T, Fass R. Step-by-step management of refractory gastresophageal reflux disease. Dis Esophagus. 2013;26(1):27-36. https://doi.org/10.1111/j.1442-2050.2011.01322.xHershcovici T, Fass R. Step-by-step management of refractory gastresophageal reflux disease. Dis Esophagus. 2013;26(1):27-36. https://doi.org/10.1111/j.1442-2050.2011.01322.xAtes F, Francis DO, Vaezi MF. Refractory gastroesophageal reflux disease: advances and treatment. Expert Rev Gastroenterol Hepatol. 2014;8(6):657-667. https://doi.org/10.1586/17474124.2014.910454Ates F, Francis DO, Vaezi MF. Refractory gastroesophageal reflux disease: advances and treatment. Expert Rev Gastroenterol Hepatol. 2014;8(6):657-667. https://doi.org/10.1586/17474124.2014.910454Delshad SD, Almario CV, Chey WD, Spiegel BMR. Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor- Refractory Symptoms. Gastroenterology. 2020;158(5):1250-1261. https://doi.org/10.1053/j.gastro.2019.12.014Delshad SD, Almario CV, Chey WD, Spiegel BMR. Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor- Refractory Symptoms. Gastroenterology. 2020;158(5):1250-1261. https://doi.org/10.1053/j.gastro.2019.12.014Gyawali CP, Roman S, Bredenoord AJ, Fox M, Keller J, Pandolfino JE, Sifrim D, Tatum R, Yadlapati R, Savarino E. Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group. Neurogastroenterol Motil. 2017;29(12):e13104. https://doi.org/10.1111/nmo.13104Gyawali CP, Roman S, Bredenoord AJ, Fox M, Keller J, Pandolfino JE, Sifrim D, Tatum R, Yadlapati R, Savarino E. Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group. Neurogastroenterol Motil. 2017;29(12):e13104. https://doi.org/10.1111/nmo.13104Scarpellini E, Ang D, Pauwels A, De Santis A, Vanuytsel T, Tack J. Management of refractory typical GERD symptoms. Nat Rev Gastroenterol Hepatol. 2016;13(5):281-294. https://doi.org/10.1038/nrgastro.2016.50Scarpellini E, Ang D, Pauwels A, De Santis A, Vanuytsel T, Tack J. Management of refractory typical GERD symptoms. Nat Rev Gastroenterol Hepatol. 2016;13(5):281-294. https://doi.org/10.1038/nrgastro.2016.50Fletcher J, Wirz A, Young J, Vallance R, McColl KE. Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal. Gastroenterology. 2001;121(4):775-783. https://doi.org/10.1053/gast.2001.27997Fletcher J, Wirz A, Young J, Vallance R, McColl KE. Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal. Gastroenterology. 2001;121(4):775-783. https://doi.org/10.1053/gast.2001.27997Beaumont H, Bennink RJ, de Jong J, Boeckxstaens GE. The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD. Gut. 2010;59(4):441-451. https://doi.org/10.1136/gut.2009.178061Beaumont H, Bennink RJ, de Jong J, Boeckxstaens GE. The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD. Gut. 2010;59(4):441-451. https://doi.org/10.1136/gut.2009.178061Rohof WO, Bennink RJ, Boeckxstaens GE3. Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach. Clin Gastroenterol Hepatol. 2014;12(7):1101-1107.https://doi.org/10.1016/j.cgh.2014.04.003Rohof WO, Bennink RJ, Boeckxstaens GE3. Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach. Clin Gastroenterol Hepatol. 2014;12(7):1101-1107.https://doi.org/10.1016/j.cgh.2014.04.003Naik RD, Evers L, Vaezi MF. Advances in the Diagnosis and Treatment of GERD: New Tricks for an Old Disease. Curr Treat Options Gastroenterol. 2019;17(1):1-17. https://doi.org/10.1007/s11938-019-00213-wNaik RD, Evers L, Vaezi MF. Advances in the Diagnosis and Treatment of GERD: New Tricks for an Old Disease. Curr Treat Options Gastroenterol. 2019;17(1):1-17. https://doi.org/10.1007/s11938-019-00213-wBoeckxstaens G, El-Serag HB, Smout AJ, Kahrilas PJ. Symptomatic reflux disease: the present, the past and the future. Gut. 2014;63(7):1185-1193. https://doi.org/10.1136/gutjnl-2013-306393Boeckxstaens G, El-Serag HB, Smout AJ, Kahrilas PJ. Symptomatic reflux disease: the present, the past and the future. Gut. 2014;63(7):1185-1193. https://doi.org/10.1136/gutjnl-2013-306393Ates F, Francis DO, Vaezi MF. Refractory gastroesophageal reflux disease: advances and treatment. Expert Rev Gastroenterol Hepatol. 2014;8(6):657-667. https://doi.org/10.1586/17474124.2014.910454Ates F, Francis DO, Vaezi MF. Refractory gastroesophageal reflux disease: advances and treatment. Expert Rev Gastroenterol Hepatol. 2014;8(6):657-667. https://doi.org/10.1586/17474124.2014.910454Vaezi MF, Richter JE, Stasney CR, Spiegel JR, Iannuzzi RA, Crawley JA, Hwang C, Sostek MB, Shaker R. Treatment of chronic posterior laryngitis with esomeprazole. Laryngoscope. 2006;116(2):254-260. https://doi.org/10.1097/01.mlg.0000192173.00498.baVaezi MF, Richter JE, Stasney CR, Spiegel JR, Iannuzzi RA, Crawley JA, Hwang C, Sostek MB, Shaker R. Treatment of chronic posterior laryngitis with esomeprazole. Laryngoscope. 2006;116(2):254-260. https://doi.org/10.1097/01.mlg.0000192173.00498.baZerbib F, Belhocine K, Simon M, Capdepont M, Mion F, Bruley des Varannes S, Galmiche JP. Clinical, but not oesophageal pH-impedance, profiles predict response to proton pump inhibitors in gastro-oesophageal reflux disease. Gut. 2012;61(4):501-506. https://doi.org/10.1136/gutjnl-2011-300798Zerbib F, Belhocine K, Simon M, Capdepont M, Mion F, Bruley des Varannes S, Galmiche JP. Clinical, but not oesophageal pH-impedance, profiles predict response to proton pump inhibitors in gastro-oesophageal reflux disease. Gut. 2012;61(4):501-506. https://doi.org/10.1136/gutjnl-2011-300798Aziz Q, Fass R, Gyawali CP, Miwa H, Pandolfino JE, Zerbib F. Functional Esophageal Disorders. Gastroenterology. 2016;150(6):1368-1379. https://doi.org/10.1053/j.gastro.2016.02.012Aziz Q, Fass R, Gyawali CP, Miwa H, Pandolfino JE, Zerbib F. Functional Esophageal Disorders. Gastroenterology. 2016;150(6):1368-1379. https://doi.org/10.1053/j.gastro.2016.02.012Цуканов В.В., Каспаров Э.В., Онучина Е.В., Васютин А.В., Буторин Н.Н., Амельчугова О.С., Тонких Ю.Л. Частота и клинические аспекты внепищеводных синдромов у пациентов с гастроэзофагеальной рефлюксной болезнью пожилого возраста. Терапевтический архив. 2016;88(2):28-32. https://doi.org/10.17116/terarkh201688228-32Tsukanov VV, Kasparov EV, Onuchina EV, Vasyutin AV, Butorin NN, Amelchugova OS, Tonkikh YuL. The frequency and clinical aspects of extraesophageal syndromes in elderly patients with gastroesophageal reflux disease. Therapeutic Archive. 2016;88(2):28-32. (In Russ.) https://doi.org/10.17116/terarkh201688228-32Spechler SJ. Refractory Gastroesophageal Reflux Disease and Functional Heartburn. Gastrointest Endosc Clin N Am. 2020;30(2):343-359. https://doi.org/10.1016/j.giec.2019.12.003Spechler SJ. Refractory Gastroesophageal Reflux Disease and Functional Heartburn. Gastrointest Endosc Clin N Am. 2020;30(2):343-359. https://doi.org/10.1016/j.giec.2019.12.003Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, Vaezi M, Sifrim D, Fox MR, Vela MF, Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018;67(7):1351-1362. https://doi.org/10.1136/gutjnl-2017-314722Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, Vaezi M, Sifrim D, Fox MR, Vela MF, Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018;67(7):1351-1362. https://doi.org/10.1136/gutjnl-2017-314722Trudgill NJ, Sifrim D, Sweis R, Fullard M, Basu K, McCord M, Booth M, Hayman J, Boeckxstaens G, Johnston BT, Ager N, De Caestecker J. British Society of Gastroenterology guidelines for oesophageal manometry and oesophageal reflux monitoring. Gut. 2019;68(10):1731-1750. https://doi.org/10.1136/gutjnl-2018-318115Trudgill NJ, Sifrim D, Sweis R, Fullard M, Basu K, McCord M, Booth M, Hayman J, Boeckxstaens G, Johnston BT, Ager N, De Caestecker J. British Society of Gastroenterology guidelines for oesophageal manometry and oesophageal reflux monitoring. Gut. 2019;68(10):1731-1750. https://doi.org/10.1136/gutjnl-2018-318115Ивашкин В.Т., Маев И.В., Трухманов А.С., Баранская Е.К., Дронова О.Б., Зайратьянц О.В., Сайфутдинов Р.Г., Шептулин А.А., Лапина Т.Л., Пирогов С.С., Кучерявый Ю.А., Сторонова О.А., Андреев Д.Н. Клинические рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению гастроэзофагеальной рефлюксной болезни. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2017;27(4):75-95 https://doi.org/10.22416/1382-4376-2017-27-4-75-95Ivashkin VT, Mayev IV, Trukhmanov AS, Baranskaya YeK, Dronova OB, Zayrat'yants OV, Sayfutdinov RG, Sheptulin AA, Lapina TL, Pirogov SS, Kucheryavyy Y., Storonova OA, Andreyev DN. Diagnostics and treatment of gastroesophageal reflux disease: clinical guidelines of the Russian gastroenterological association. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii. 2017;27(4):75-95. (In Russ.) https://doi.org/10.22416/1382-4376-2017-27-4-75-95De Groot NL, Burgerhart JS, Van De Meeberg PC, de Vries DR, Smout AJ, Siersema PD. Systematic review: the effects of conservative and surgical treatment for obesity on gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2009;30(11-12):1091-1102. https://doi.org/10.1111/j.1365-2036.2009.04146.xDe Groot NL, Burgerhart JS, Van De Meeberg PC, de Vries DR, Smout AJ, Siersema PD. Systematic review: the effects of conservative and surgical treatment for obesity on gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2009;30(11-12):1091-1102. https://doi.org/10.1111/j.1365-2036.2009.04146.xEherer AJ, Netolitzky F, Högenauer C, Puschnig G, Hinterleitner TA, Scheidl S, Kraxner W, Krejs GJ, Hoffmann KM. Positive effect of abdominal breathing exercise on gastroesophageal reflux disease: a randomized, controlled study. Am J Gastroenterol. 2012;107(3):372-378. https://doi.org/10.1038/ajg.2011.420Eherer AJ, Netolitzky F, Högenauer C, Puschnig G, Hinterleitner TA, Scheidl S, Kraxner W, Krejs GJ, Hoffmann KM. Positive effect of abdominal breathing exercise on gastroesophageal reflux disease: a randomized, controlled study. Am J Gastroenterol. 2012;107(3):372-378. https://doi.org/10.1038/ajg.2011.420Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-328. https://doi.org/10.1038/ajg.2012.444Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-328. https://doi.org/10.1038/ajg.2012.444Manabe N, Haruma K, Ito M, Takahashi N, Takasugi H, Wada Y, Nakata H, Katoh T, Miyamoto M, Tanaka S. Efficacy of adding sodium alginate to omeprazole in patients with nonerosive reflux disease: a randomized clinical trial. Dis Esophagus. 2012;25(5):373-380. https://doi.org/10.1111/j.1442-2050.2011.01276.xManabe N, Haruma K, Ito M, Takahashi N, Takasugi H, Wada Y, Nakata H, Katoh T, Miyamoto M, Tanaka S. Efficacy of adding sodium alginate to omeprazole in patients with nonerosive reflux disease: a randomized clinical trial. Dis Esophagus. 2012;25(5):373-380. https://doi.org/10.1111/j.1442-2050.2011.01276.xTack J, Zaninotto G. Therapeutic options in oesophageal dysphagia. Nat Rev Gastroenterol Hepatol. 2015;12(6):332-341. https://doi.org/10.1038/nrgastro.2015.45Tack J, Zaninotto G. Therapeutic options in oesophageal dysphagia. Nat Rev Gastroenterol Hepatol. 2015;12(6):332-341. https://doi.org/10.1038/nrgastro.2015.45Koek GH, Sifrim D, Lerut T, Janssens J, Tack J. Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno- gastro-oesophageal reflux refractory to proton pump inhibitors. Gut. 2003;52(10):1397-1402. https://doi.org/10.1136/gut.52.10.1397Koek GH, Sifrim D, Lerut T, Janssens J, Tack J. Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno- gastro-oesophageal reflux refractory to proton pump inhibitors. Gut. 2003;52(10):1397-1402. https://doi.org/10.1136/gut.52.10.1397Цуканов В.В., Онучина Е.В., Каспаров Э.В., Васютин А.В., Тонких Ю.Л. Опыт длительной терапии пациентов с пищеводом Барретта. Фарматека. 2015;(2):62-65Tsukanov VV, Onuchina EV, Kasparov EV, Vasyutin AV, Tonkikh JL. Experience with long-term treatment of patients with Barrett's esophagus. Farmateka. 2015;(2):62-65. (In Russ.)Эмбутниекс Ю.В., Валитова Э.Р., Бордин Д.С. Новый подход к лечению гастроэзофагеальной рефлюксной болезни: защита слизистой оболочки пищевода. Эффективная фармакотерапия. 2019;15(18):16-22. https://doi.org/10.33978/2307-3586-2019-15-18-16-22Embutniyeks YuV, Valitova ER, Bordin DS. The New Approach to the Treatment of Gastroesophageal Reflux Disease: the Protection of the Esophageal Mucosa. Effektivnaya farmakoterapiya. 2019;15(18):16-22. (In Russ.) https://doi.org/10.33978/2307-3586-2019-15-18-16-22Forcelini CM, Tomiozzo JC Jr, Farré R, Van Oudenhove L, Callegari- Jacques SM, Ribeiro M, Madalosso BH, Fornari F. Effect of nortriptyline on brain responses to painful esophageal acid infusion in patients with non-erosive reflux disease. Neurogastroenterol Motil. 2014;26(2):187-195. DOI: 10.1111/nmo.12251Forcelini CM, Tomiozzo JC Jr, Farré R, Van Oudenhove L, Callegari- Jacques SM, Ribeiro M, Madalosso BH, Fornari F. Effect of nortriptyline on brain responses to painful esophageal acid infusion in patients with non-erosive reflux disease. Neurogastroenterol Motil. 2014;26(2):187-195. DOI: 10.1111/nmo.12251Moore M, Afaneh C, Benhuri D, Antonacci C, Abelson J, Zarnegar R. Gastroesophageal reflux disease: A review of surgical decision making. World J Gastrointest Surg. 2016;8(1):77-83. https://doi.org/10.4240/wjgs.v8.i1.77Moore M, Afaneh C, Benhuri D, Antonacci C, Abelson J, Zarnegar R. Gastroesophageal reflux disease: A review of surgical decision making. World J Gastrointest Surg. 2016;8(1):77-83. https://doi.org/10.4240/wjgs.v8.i1.77Spechler SJ, Hunter JG, Jones KM, Lee R, Smith BR, Mashimo H, Sanchez VM, Dunbar KB, Pham TH, Murthy UK, Kim T, Jackson CS, Wallen JM, von Rosenvinge EC, Pearl JP, Laine L, Kim AW, Kaz AM, Tatum RP, Gellad ZF, Lagoo-Deenadayalan S, Rubenstein JH, Ghaferi AA, Lo WK, Fernando RS, Chan BS, Paski SC, Provenzale D, Castell DO, Lieberman D, Souza RF, Chey WD, Warren SR, Davis-Karim A, Melton SD, Genta RM, Serpi T, Biswas K, Huang GD. Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn. N Engl J Med. 2019;381(16):1513-1523. https://doi.org/10.1056/NEJMoa1811424Spechler SJ, Hunter JG, Jones KM, Lee R, Smith BR, Mashimo H, Sanchez VM, Dunbar KB, Pham TH, Murthy UK, Kim T, Jackson CS, Wallen JM, von Rosenvinge EC, Pearl JP, Laine L, Kim AW, Kaz AM, Tatum RP, Gellad ZF, Lagoo-Deenadayalan S, Rubenstein JH, Ghaferi AA, Lo WK, Fernando RS, Chan BS, Paski SC, Provenzale D, Castell DO, Lieberman D, Souza RF, Chey WD, Warren SR, Davis-Karim A, Melton SD, Genta RM, Serpi T, Biswas K, Huang GD. Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn. N Engl J Med. 2019;381(16):1513-1523. https://doi.org/10.1056/NEJMoa1811424Buckley FP, Bell RCW, Freeman K, Doggett S, Heidrick R. Favorable results from a prospective evaluation of 200 patients with large hiatal hernias undergoing LINX magnetic sphincter augmentation. Surg Endosc. 2018;32(4):1762-1768. https://doi.org/10.1007/s00464-017-5859-4Buckley FP, Bell RCW, Freeman K, Doggett S, Heidrick R. Favorable results from a prospective evaluation of 200 patients with large hiatal hernias undergoing LINX magnetic sphincter augmentation. Surg Endosc. 2018;32(4):1762-1768. https://doi.org/10.1007/s00464-017-5859-4

The authors declare that there are no conflicts of interest present.