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Open research questions in Gastroesophageal reflux and treatments

172 gap statements mined from Gastroesophageal reflux and treatments papers in our 4.5M-paper local library, which holds 1,012 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • There is a need for accurate screening and identification of patients with extraesophageal symptoms who may benefit from acid suppression therapy. The current diagnostic tools for gastroesophageal reflux disease have limitations in terms of sensitivity and specificity.

    A model combining nocturnal baseline impedance, post-reflux swallow-induced peristaltic wave, and acid exposure time enhances prediction of proton pump inhibitor response for extraesophageal symptoms in a Chinese population · 2026 · DOI

  • Finally, the prediction model was not validated in an external cohort, and long-term follow-up data on model-guided interventions are lacking; thus, its ability to reduce LPRD incidence or improve clinical outcomes remains to be confirmed.

    Current status and influencing factors of laryngopharyngeal reflux disease in outpatients with laryngeal diseases: key considerations for clinical practice · 2026 · DOI

  • There is a need to evaluate the efficacy of combination therapy comprising PPIs with prokinetic agents in GERD patients. There is a lack of studies comparing the therapeutic efficacy of different prokinetic agents in combination with PPIs.

    Comparative Study of Efficacy of Addition of Prokinetics to Proton Pump Inhibitors in Patients with Gastroesophageal Reflux Disease · 2026 · DOI

  • Further research is needed to confirm the findings and to determine the optimal treatment strategy for patients with COPD and GERD. Studies should investigate the mechanisms by which P-CABs may reduce the risk of respiratory events. Research should focus on identifying potential subgroups that may benefit from P-CAB or PPI treatment.

    Comparative risk of pneumonia and acute exacerbation between P-CAB and PPI use in patients with COPD and GERD · 2026 · DOI

  • There is a need to assess the dynamics of quality of life in patients after laparoscopic fundoplication for hiatal hernia. There is a lack of studies on the use of the GERD-HRQL questionnaire in assessing quality of life in patients with hiatal hernia.

    QUALITY OF LIFE IN PATIENTS AFTER LAPAROSCOPIC FUNDOPLICATION FOR HIATAL HERNIA BASED ON GERD-HRQL QUESTIONNAIRE DATA · 2026 · DOI

  • Future research should prioritize standardized phenotyping and durable outcome reporting. Prospective studies are needed to refine patient selection and determine the optimal timing of intervention. The application of emerging approaches, such as magnetic sphincter augmentation, should be further explored.

    The pathogenesis and surgical treatment progress of gastroesophageal reflux disease · 2026 · DOI

  • The concept of “asymptomatic elective repair” has not been fully explored in hiatal hernia patients. Standardized phenotyping and durable outcome reporting are needed to refine patient selection and determine the optimal timing of intervention.

    The pathogenesis and surgical treatment progress of gastroesophageal reflux disease · 2026 · DOI

  • Lack of specificity in diagnostic tools. Risk of overtreatment.

    Acid Reflux and ENT manifestations: A review of Laryngopharyngeal Reflux · 2026 · DOI

  • There is uncertainty regarding the implications of chronic PPI therapy on the onset of IBD. The association between PPI use and IBD risk is not well understood.

    Association between proton pump inhibitor use and the risk of inflammatory bowel disease: A systematic review and meta-analysis · 2026 · DOI

  • The relationship between GERD and demographic and anthropometric parameters is not well understood. There is a need for larger studies using advanced diagnostic modalities to clarify the associations between GERD and these factors.

    Prevalence and Severity of Gastroesophageal Reflux Disease in Adults Using Gastroesophageal Reflux Scintigraphy · 2026 · DOI

  • Current empiric-based, non-standardized GERD management practices are highly variable and untested for safety and efficacy. Prior trials have not adequately assessed the safety and efficacy of using acid suppression in this population.

    GERD management in neonatal ICU infants: study protocol for a randomized controlled trial comparing maturation, added rice starch formula and proton pump inhibitors · 2026 · DOI

  • The study aims to address the gap in understanding the role of laryngopharyngeal reflux in RLP. The current literature does not fully explain the variability in disease severity and recurrence. Additional cofactors, such as laryngopharyngeal reflux, may contribute to disease persistence and recurrence.

    Immunohistochemical detection of pepsin in recurrent laryngeal papillomatosis: findings consistent with laryngopharyngeal reflux exposure · 2026 · DOI

  • Finally, immunohistochemistry has inherent technical limitations (pre-analytical variability, staining thresholds, and potential antibody-related specificity issues), and some selection bias is possible because consecutive case inclusion could not be confirmed from the available records.

    Immunohistochemical detection of pepsin in recurrent laryngeal papillomatosis: findings consistent with laryngopharyngeal reflux exposure · 2026 · DOI

  • The need to identify risk factors for the development of metabolic disorders in military personnel with erosive-ulcerative lesions of the esophagogastroduodenal zone. The lack of understanding of the effect of wartime factors on the development of metabolic disorders in military personnel.

    Influence of wartime factors on the development of metabolic disorders in military servicemen with erosive-ulcerative lesions of the esophagogastroduodenal zone · 2026 · DOI

  • The risk factors and clinical consequences of DGCE after esophagectomy remain unclear. There is no clear consensus regarding optimal management strategies for DGCE.

    Clinical significance and predictive factors of delayed gastric conduit emptying after esophagectomy · 2026 · DOI

  • Delayed gastric conduit emptying (DGCE) is a functional complication after esophagectomy that can cause nutritional and respiratory issues, but its risk factors remain unclear.

    Clinical significance and predictive factors of delayed gastric conduit emptying after esophagectomy · 2026 · DOI

  • The relationship between GERD and pancreatitis is not well understood. Few studies have investigated the potential causal relationship between GERD and pancreatitis. The mediating role of cholelithiasis in the causal pathway from GERD to pancreatitis is not well understood.

    Mediation analysis of the causal pathway from gastroesophageal reflux disease to pancreatitis: A Mendelian randomization study · 2026 · DOI

  • Further verification of the proposed explanations involving bread, wheat, fermentable oligosaccharides, disaccharides, monosaccharides and polyols, yeast fermentation, delayed gastric emptying, and gluten sensitivity is needed.

    Dietary patterns and gastroesophageal reflux disease in Sri Lanka: A regional food culture perspective · 2026 · DOI

  • The associations among specific food, eating behavior, nutritional intake and GERD remain inconsistent. There is a lack of large-sample studies from non-Western countries that are grounded in local food culture.

    Dietary patterns and gastroesophageal reflux disease in Sri Lanka: A regional food culture perspective · 2026 · DOI

  • Patients presenting solely with atypical symptoms should be evaluated through a multidisciplinary approach.

    Vietnam Association of Gastroenterology (VNAGE) guideline on the management of gastroesophageal reflux disease · 2026 · DOI

  • The generalizability of the findings to specific clinical presentations, such as typical symptomatic GERD, atypical reflux symptoms, or incidental/asymptomatic RE, remains uncertain. Clinical utility remains uncertain and requires external validation, recalibration, and assessment of decision-analytic benefit.

    Metabolic correlates of endoscopy-confirmed reflux esophagitis in hospital-based patients with type 2 diabetes mellitus · 2026 · DOI

  • Future large-scale randomized trials are recommended to further validate the outcomes. The study's findings can be used to refine guidelines for prokinetic use in GERD management.

    Comparative Study of Efficacy of Addition of Prokinetics to Proton Pump Inhibitors in Patients with Gastroesophageal Reflux Disease · 2026 · DOI

  • The study used observational data and may be subject to confounding variables. The study had a limited follow-up period. The study did not include patients who did not receive P-CAB or PPI treatment.

    Comparative risk of pneumonia and acute exacerbation between P-CAB and PPI use in patients with COPD and GERD · 2026 · DOI

  • In this context, systematic screening for GERD symptoms and sleep disturbances could facilitate early detection and timely management, considering that both are potentially modifiable factors and may reinforce each other.

    Gastroesophageal reflux symptoms and sleep quality among medical students at a private university in Lima, Peru: A cross-sectional study · 2026 · DOI

  • Future studies integrating individual-level data and experimental validation are warranted to further elucidate the mechanistic role of cholelithiasis in the GERD-pancreatitis…

    Mediation analysis of the causal pathway from gastroesophageal reflux disease to pancreatitis: A Mendelian randomization study · 2026 · DOI

Most-cited papers in Gastroesophageal reflux and treatments

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Open questions raised by papers listed on this page include: (1) There is a need for accurate screening and identification of patients with extraesophageal symptoms who may benefit from acid suppression therapy (“A model combining nocturnal baseline impedance, post-reflux swallow-induced…”, 2026); (2) The prediction model was not validated in an external cohort, and long-term follow-up data on model-guided interventions are lacking; thus, its ability to reduce LPRD incidence or improve clinical outcomes remains to be confirmed (“Current status and influencing factors of laryngopharyngeal reflux disease in…”, 2026); (3) There is a need to evaluate the efficacy of combination therapy comprising PPIs with prokinetic agents in GERD patients (“Comparative Study of Efficacy of Addition of Prokinetics to Proton Pump…”, 2026); (4) Further research is needed to confirm the findings and to determine the optimal treatment strategy for patients with COPD and GERD (“Comparative risk of pneumonia and acute exacerbation between P-CAB and PPI use…”, 2026); (5) There is a need to assess the dynamics of quality of life in patients after laparoscopic fundoplication for hiatal hernia (“QUALITY OF LIFE IN PATIENTS AFTER LAPAROSCOPIC FUNDOPLICATION FOR HIATAL HERNIA…”, 2026). 172 gap statements have been mined from Gastroesophageal reflux and treatments papers in our 4.5M-paper local library, which holds 1,012 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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