СУТОЧНАЯ МНОГОКАНАЛЬНАЯ РН-ИМПЕДАНСОМЕТРИЯ ПИЩЕВОДА В ДИАГНОСТИКЕ ГАСТРОЭЗОФАГЕАЛЬНОЙ РЕФЛЮКСНОЙ БОЛЕЗНИ (КЛИНИЧЕСКИЕ СЛУЧАИ)

Background. Gastroesophageal reflux disease (GERD) is an urgent problem of modern gastroenterology as well as the most common pathology of the upper gastrointestinal tract; it is a chronic disease that significantly reduces the patient's quality of life, increases the risk of developing Barrett's esophagus and esophageal adenocarcinoma. Objective. To assess the potentials of multichannel intraluminal pH impedance monitoring in the diagnosis of esophageal diseases. Material and methods. In 3 patients with clinical and endoscopic signs of GERD esophageal multichannel intraluminal pH-impedance monitoring was performed using the diagnostic equipment Digitrapper pH-Z from Given Imaging (USA). Results. 24-hour esophageal pH monitoring enabled to verify the diagnosis of GERD, to reveal a hypersensitive esophagus and manifestations of nocturnal acid breakthrough. Conclusions. Multichannel intraluminal pH-impedance monitoring is the "gold standard" for the diagnosis of esophageal diseases; it significantly expands opportunities of gastroenterologists in the treatment of GERD.

Screening and Evaluating Novel Autoantibodies Based on Proteomic Chips in Diagnosis of Esophageal Squamous Cell Carcinoma

Background More and more studies have confirmed that TAAbs could be used as potential biomarkers for tumor patients. The aim of this study is to identify novel TAAbs through proteomic chips and construct a diagnostic model to discriminate esophageal squamous cell carcinoma (ESCC) cases from benign esophageal diseases cases and normal controls (NCs). Methods The human proteomic chips were used to screen TAAbs. Enzyme-linked immunosorbent assay (ELISA) was adopted to verify and validate the candidate TAAbs which were screened by the chips in verification phase (90 ESCC cases and 90 NCs) and validation phase (126 ESCC cases, 237 benign esophageal diseases cases and 126 NCs). Based on the candidate TAAbs, then the diagnostic model for ESCC was constructed by logistic regression analysis in the training group and validated in the testing group. Results Firstly, thirteen potential candidate TAAbs were identified by proteomic chips. In verification phase, the titers of six TAAbs (anti-MAGEA1, anti-VCL, anti-PRKCZ, anti-TP53, anti-NFKB1 and anti- MAGEA4) in ESCC cases were higher than those in NCs while other seven TAAbs showed no difference. Subsequently, six candidate TAAbs were validated further in validation phase. Finally, the logistic regression model with 3 TAAbs (anti-MAGEA1, anti-VCL, anti-TP53) could discriminate ESCC cases from NCs with area under curve(AUC)of 0.80 in the training group and 0.73 in the testing group, respectively. Meanwhile, the model could discriminate ESCC cases from benign esophageal diseases cases with AUC of 0.74. Conclusion The study has identified six novel TAAbs through protein chips and constructed a diagnostic model. The panel showed great performance to distinguish ESCC cases from benign esophageal diseases cases and NCs.

Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: a case-control study

Background Plasma cell-free DNA (cfDNA) methylation has shown promising results in the early detection of multiple cancers recently. Here, we conducted a study to investigate the performance of cfDNA methylation in the early detection of esophageal cancer (ESCA). Methods Specific methylation markers for ESCA were identified and optimized based on esophageal tumor and paired adjacent tissues (n = 24). Age-matched participants with ESCA (n = 85), benign esophageal diseases (n = 10), and healthy controls (n = 125) were randomized into the training and test sets to develop a classifier to differentiate ESCA from healthy controls and benign esophageal disease. The classifier was further validated in an independent plasma cohort of ESCA patients (n = 83) and healthy controls (n = 98). Results In total, 921 differentially methylated regions (DMRs) between tumor and adjacent tissues were identified. The early detection classifier based on those DMRs was first developed and tested in plasma samples, discriminating ESCA patients from benign and healthy controls with a sensitivity of 76.2% (60.5–87.9%) and a specificity of 94.1% (85.7–98.4%) in the test set. The performance of the classifier was consistent irrespective of sex, age, and pathological diagnosis (P > 0.05). In the independent plasma validation cohort, similar performance was observed with a sensitivity of 74.7% (64.0–83.6%) and a specificity of 95.9% (89.9–98.9%). Sensitivity for stage 0–II was 58.8% (44.2–72.4%). Conclusion We demonstrated that the cfDNA methylation patterns could distinguish ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Further prospective evaluation of the classifier in the early detection of ESCAs in high-risk individuals is warranted.

Inhibition of NHE-1 Increases Smoke-Induced Proliferative Activity of Barrett’s Esophageal Cell Line

Several clinical studies indicate that smoking predisposes its consumers to esophageal inflammatory and malignant diseases, but the cellular mechanism is not clear. Ion transporters protect esophageal epithelial cells by maintaining intracellular pH at normal levels. In this study, we hypothesized that smoking affects the function of ion transporters, thus playing a role in the development of smoking-induced esophageal diseases. Esophageal cell lines were treated with cigarettesmoke extract (CSE), and the viability and proliferation of the cells, as well as the activity, mRNA and protein expression of the Na+/H+ exchanger-1 (NHE-1), were studied. NHE-1 expression was also investigated in human samples. For chronic treatment, guinea pigs were exposed to tobacco smoke, and NHE-1 activity was measured. Silencing of NHE-1 was performed by using specific siRNA. CSE treatment increased the activity and protein expression of NHE-1 in the metaplastic cells and decreased the rate of proliferation in a NHE-1-dependent manner. In contrast, CSE increased the proliferation of dysplastic cells independently of NHE-1. In the normal cells, the expression and activity of NHE-1 decreased due to in vitro and in vivo smoke exposure. Smoking enhances the function of NHE-1 in Barrett’s esophagus, and this is presumably a compensatory mechanism against this toxic agent.

Mouse organoid culture is a suitable model to study esophageal ion transport mechanisms

Altered esophageal ion transport mechanisms play a key role in inflammatory and cancerous diseases of the esophagus, but epithelial ion processes have been less studied in the esophagus because of the lack of a suitable experimental model. In this study, we generated 3D esophageal organoids (EOs) from two different mouse strains and characterized the ion transport processes of the EOs. EOs form a cell-filled structure with a diameter of 250-300 µm and generated from epithelial stem cells as shown by FACS analysis. Using conventional PCR and immunostaining, the presence of Slc26a6 Cl−/HCO3− anion exchanger (AE), Na+/H+ exchanger (NHE), Na+/HCO3- cotransporter (NBC), cystic fibrosis transmembrane conductance regulator (CFTR) and anoctamin 1 Cl− channels were detected in EOs. Microfluorimetric techniques revealed high NHE, AE, and NBC activities, whereas that of CFTR was relatively low. In addition, inhibition of CFTR led to functional interactions between the major acid-base transporters and CFTR. We conclude that EOs provide a relevant and suitable model system for studying the ion transport mechanisms of esophageal epithelial cells, and they can be also used as preclinical tools to assess the effectiveness of novel therapeutic compounds in esophageal diseases associated with altered ion transport processes.

Functional Luminal Imaging Probe (FLIP) as an Adjunctive Modality in Evaluation of Esophageal Dysmotility

The Functional Luminal Imaging Probe (FLIP) has emerged as a valuable adjunctive tool in the evaluation of esophageal diseases. Using volumetric distension, FLIP can assess secondary peristalsis and detect esophageal abnormalities that may not be evaluated by high-resolution manometry (HRM). In certain clinical settings, FLIP may allow for deferral of HRM. In therapy for esophageal diseases, FLIP has demonstrated value for its real-time interpretation, which can be used intra-procedurally to tailor therapy and to predict post-therapy outcomes. The future of FLIP looks promising as surgeons and gastroenterologists place increasing emphasis on non-manometric data to diagnose esophageal motility disorders.

Tunnel endoscopic interventions in esophageal diseases

The aim of the study is the evaluation of results of endoscopic tunnel interventions in submucosal tumors and achalasia.Material and methods. Endoscopic tunnel interventions during 2017–2020 years were performed in 80 patients (34-men, 46-women). The duration of the age ranged from 15 to 72 years. The indications for interventions were: achalasia in 53, subepithelial tumors in 27.Results. During the intervention, complications occurred in 22 patients. Among the complications: carboxyperitoneum in 16 cases, carboxytorax in 2, esophageal mucosa perforation in 2, bleeding moderate intensity bleeding in 2. Most of the complications (20) were in patients with esophageal achalasia. Postoperative complications were observed in two patients operated for esophageal achalasia (bleeding and hematoma, esophageal mucosa necrosis). All patients were treated by using conservative methods. The results of the interventions were assessed in terms of 1 month to 3 years. There were no violations of food or liquid the passage through the cardia. Patients after operation for submucous tumors of the esophagus had no complaints. The main complaint of patients after myotomy was heartburn. Endoscopic examination revealed erosive reflux esophagitis (A-C) in 18 patients.Conclusion. Tunnel endoscopic interventions in patients with esophageal achalasia and submucous tumors are highly effective and low-traumatic, allowing relatively safe restoration of the patency of the cardia and removal of the subepithelial neoplasm. The problem of gastroesophageal reflux after oral endoscopic myotomy requires further accumulation of data in order to develop optimal tactics. The limiting factor for the these operations performance is the material and technical equipment of medical institutions and the lack of trained specialists.

Differences in Gut Virome Related to Barrett Esophagus and Esophageal Adenocarcinoma

The relationship between viruses (dominated by bacteriophages or phages) and lower gastrointestinal (GI) tract diseases has been investigated, whereas the relationship between gut bacteriophages and upper GI tract diseases, such as esophageal diseases, which mainly include Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), remains poorly described. This study aimed to reveal the gut bacteriophage community and their behavior in the progression of esophageal diseases. In total, we analyzed the gut phage community of sixteen samples from patients with esophageal diseases (six BE patients and four EAC patients) as well as six healthy controls. Differences were found in the community composition of abundant and rare bacteriophages among three groups. In addition, the auxiliary metabolic genes (AMGs) related to bacterial exotoxin and virulence factors such as lipopolysaccharides (LPS) biosynthesis proteins were found to be more abundant in the genome of rare phages from BE and EAC samples compared to the controls. These results suggest that the community composition of gut phages and functional traits encoded by them were different in two stages of esophageal diseases. However, the findings from this study need to be validated with larger sample sizes in the future.