Background/AimsGastroesophageal reflux disease is frequently observed and has no definitive treatment.There are 2 main views on the pathogenesis of gastroesophageal reflux disease.The first is that epithelial damage starts from the mucosa by acidic-peptic damage and the inflammatory response of granulocytes.The other view is that T-lymphocytes attract chemoattractants from the basal layer to the mucosa, and granulocytes do not migrate until damage occurs.We aim to investigate the inflammatory processes occurring in the esophageal epithelium of the phenotypes at the molecular level.We also examined the effects of these changes on tissue integrity. MethodsPatients with mild and severe erosive reflux, nonerosive reflux, reflux hypersensitivity, and functional heartburn were included.Inflammatory gene expressions (JAK/STAT Signaling and NFKappaB Primer Libraries), chemokine protein levels, and tissue integrity were examined in the esophageal biopsies. ResultsThere was chronic inflammation in the severe erosion group, the acute response was also triggered.In the mild erosion group, these 2 processes worked together, but homeostatic cytokines were also secreted.In nonerosive groups, T-lymphocytes were more dominant.In addition, the inflammatory response was highly triggered in the reflux hypersensitivity and functional heartburn groups, and it was associated with physiological reflux exposure and sensitivity. Conclusions"Microinflammation" in physiological acid exposure groups indicate that even a mild trigger is sufficient for the initiation and progression of inflammatory activity.Additionally, the antiinflammatory cytokines were highly increased.The results may have a potential role in the treatment of heartburn symptoms and healing of the mucosa.
Amaç: Dünya genelinde yaklaşık %1’lik bir prevelansa sahip olan çölyak hastalığı, ülkemizde de sık görülmekte ancak tanıda gözden kaçabilmektedir. Asemptomatik çölyak hastalığının yetişkin bireylerde daha sık görülmesi de tanıyı zorlaştırmaktadır. Bu nedenle çölyak hastalığının farkındalığını arttırmak ve hastalığının farkında olmayan bireylerin tanı almasını sağlamak amacıyla Ege Üniversitesi Tıp Fakültesi bünyesinde bir anket ve bilgilendirme çalışması düzenlenmiştir. Gereç ve Yöntem: Çalışmamızda yaklaşık 550 tıp fakültesi öğrencisine ayrıntılı çölyak semptom anketi uygulanmış ve semptom pozitifliği belirlenen 110 birey Ege Üniversitesi Tıp Fakültesi Gastroenteroloji Kliniği’ne davet edilmiştir. Bulgular: Davetler sonucunda yalnızca 36 kişi kliniğimize ziyaret gerçekleştirmiştir. Bu ziyaretler esnasında hastaların anemnezleri sonrası serumlarında çölyak antikorları incelenmiştir. Çalışma sonucunda çölyak ilişkili klinik bulgular ve riskler göstermelerine rağmen hiçbir hastada çölyak serolojisine rastlanmamıştır. Bu kişilerin ilerleyen dönemlerde semptom pozitifliği devam etmesi durumunda tekrar kliniğe davet edilmeleri planlanmıştır. Ayrıca bu kişilerin çölyak dışı gluten intoleranslarının olabileceği düşünülmüştür. Sonuç: Ülkemizde tıp fakültesi öğrencileri arasında ilk defa gerçekleştirilen çölyak semptom taraması çalışmasının, ilerleyen dönemlerde merkez kampüs kapsamında genişletilerek tekrarlanması planlanmaktadır. Bunların dışında, yapılan bu çalışma ile tıp fakültesi öğrencilerinin sahip olduğu birçok hastalık ve tıbbi şikâyetin sıklıklarına yönelik veriler elde edilmiştir.
Objective: Manometric studies identify esophageal motility disorders based on ten 'single water swallows' (SWS).Adjunctive testing by 'multiple water swallows' (MWS) may increase diagnostic sensitivity.This study assessed the clinical utility of MWS in patients referred for evaluation of esophageal symptoms.Methods: Prospective cohort study of patients referred for physiologic investigation of dysphagia and/or reflux symptoms.Normal values were also acquired.High Resolution Manometry (HRM) with two 200 mL MWS was performed in the seated position.Diagnosis was established from SWS by the Chicago Classification.Integrated Relaxation Pressure (IRP) during MWS and distal contractile integral (DCI) of the MWS and SWS after-contraction were compared.Abnormal MWS findings included (i) failure of EGJ relaxation; (ii) incomplete inhibition of contractility (iii) failure to augment DCI in after contraction.Results: 178 patients (76 [43%] male; age 54.3 AE 16.6 years) and 67 controls (29 [43%] male; age 42.3 AE 14.5 years) were studied.Compared to SWS, MWS reduced IRP in controls and all patient groups, except those with achalasia (p < 0.001).Failure to suppress contractions during MWS was seen only in achalasia type III, spasm and hypertensive motility disorders (p < 0.001).Effective MWS after-contraction was present in controls more often than in patient groups (overall, p < 0.001).Conclusion: MWS serves an adjunctive role in the evaluation of patients with esophageal symptoms.
Breakthrough symptoms are thought to occur in roughly half of all gastroesophageal reflux disease (GERD) patients despite maximal acid suppression (proton pump inhibitor, PPI) therapy. Topical alginates have recently been shown to enhance mucosal defense against acid-pepsin insult during GERD. We aimed to examine potential alginate protection of transcriptomic changes in a cell culture model of PPI-recalcitrant GERD. Immortalized normal-derived human esophageal epithelial cells underwent pretreatment with commercial alginate-based anti-reflux medications (Gaviscon Advance or Gaviscon Double Action), a matched-viscosity placebo control, or pH 7.4 buffer (sham) alone for 1 min, followed by exposure to pH 6.0 + pepsin or buffer alone for 3 min. RNA sequencing was conducted, and Ingenuity Pathway Analysis was performed with a false discovery rate of ≤0.01 and absolute fold-change of ≥1.3. Pepsin-acid exposure disrupted gene expressions associated with epithelial barrier function, chromatin structure, carcinogenesis, and inflammation. Alginate formulations demonstrated protection by mitigating these changes and promoting extracellular matrix repair, downregulating proto-oncogenes, and enhancing tumor suppressor expression. These data suggest molecular mechanisms by which alginates provide topical protection against injury during weakly acidic reflux and support a potential role for alginates in the prevention of GERD-related carcinogenesis.
Introduction: The major noxious agents of Gastroesophageal reflux disease (GERD) on the esophageal epithelium are gastric acid and pepsin. Nevertheless, there is no precise information about pepsin concentrations in gastric juice. We aim to address the pepsin values and pH results among subtypes of GERD and functional heartburn. Methods: 46 patients with GERD (23 erosive reflux disease LA grade A/B (ERD-A/B), 5 ERD-C/D, 14 nonerosive reflux disease-NERD, 4 esophageal hypersensitivity-EH), 8 functional heartburn (FH) and 17 healthy controls (HC) were included into the study. Upper gastrointestinal endoscopies were performed off PPI. Patients were instructed not to aspirate the local anaesthetic solution and biopsy channel of the endoscope was dried before the suction. The gastric juices from the subjects were aspirated during endoscopy into a special beaker and their pH values were measured immediately. The specimens were analysed using the Peptest lateral flow device (RD Biomed Ltd UK), a colorimetric assay containing two unique human monoclonal antibodies that capture and detect pepsin protein. Results: There were no significance between pepsin levels in any GERD phenotypes, FH and healthy controls (Table 1). The pH results of patients with ERD (1.8±0.6) were significantly lower versus HC (2.6±1.5). The pH levels of the esophageal hypersensitivity (1.5±0.2) were significantly decreased when compared to HC (2.6±1.6) and also true NERD (4.0±2.0).Table: No Caption availableConclusion: Pepsin may be considered a damaging factor in pathophysiology of GERD, but we could not find any difference between GERD phenotypes and unaffected controls. NERD group had less gastric acid versus other groups but this finding needs more studies to confirm.
