Refractory Gastroesophageal Reflux Disease: A Management Update

Abstract

Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with “reflux-like PPI-refractory symptoms.” Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.

Local inflammatory response to gastroesophageal reflux: Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data

“…The obtained results may be of use for the search of new treatment options in cases where refractory symptoms of GERD are present[ 30 ]. In such cases, the use of immune modulators affecting local immune response may help to achieve better results[ 26 ].…”

Gastrointestinal motor disorders: treatment with prokinetics

“…В недавно вышедших рекомендациях по ведению пациентов с функциональной диспепсией, основанных на доказательной медицине, в качестве терапии второй линии рекомендуется применение прокинетических препаратов, в частности антагонистов дофаминовых рецепторов (уровень доказательств B) и агонистов 5-НТ 4 -рецепторов Обзоры / Review Articles (уровень доказательств B) [51]. Что касается обновленных рекомендаций по диагностике и лечению рефрактерной гастроэзофагеальной рефлюксной болезни (ГЭРБ), то добавление прокинетиков в схему лечения пациентов не позволяло достигать лучшего контроля за симптомами заболевания, однако способствовало улучшению показателей качества жизни [52]. В недавно проведенном метаанализе [53] публикаций, включающих рандомизированные контролируемые исследования по сравнению комбинированного применения ингибиторов протонной помпы (ИПП) плюс прокинетик с монотерапией ИПП в отношении общего улучшения симптомов ГЭРБ, проводился анализ 16 исследований с участием 1446 пациентов (719 в группе ИПП плюс прокинетик и 727 в группе монотерапии ИПП).…”

Clinical use of mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index for the diagnosis of gastro-esophageal reflux disease

“…However, NERD is an "umbrella term" which includes heterogeneous subpopulations [23]. Most patients with endoscopy-negative heartburn are classified as NERD based on abnormal acid exposure at pH or impedance-pH (MII-pH) monitoring [23,24], others have RH based on normal EGDS, normal reflux monitoring, and a positive correlation between reflux episodes and symptoms occurrence at MII-pH [25]. Patients with normal EGDS and normal reflux monitoring without reflux-symptom correlation are diagnosed with functional heartburn (FH), which is considered a separate entity from GERD [26].…”