Search

Changes in expression of long non-coding RNAs (lncRNAs) in plasma exosomes can be useful for diagnosis of cancer patients. Here, we conducted a four-stage study to identify plasma exosome lncRNAs with diagnostic potential in esophageal squamous cell carcinoma (ESCC). First, plasma exosome lncRNA expression profiles were examined in ESCC patients, esophagitis patients, and healthy controls using RNA sequencing. Differentially expressed plasma exosome lncRNAs from the lncRNA expression profile were then evaluated by qRT-PCR in a large cohort of ESCC patients, esophagitis patients, and healthy controls. Expression levels of the lncRNAs NR_039819, NR_036133, NR_003353, ENST00000442416.1, and ENST00000416100.1 were significantly higher in exosomes from ESCC patients than non-cancer controls. We also confirmed that levels of these five plasma exosome lncRNAs decreased markedly in ESCC patients after surgery. Our results suggest that these five exosome lncRNAs may serve as highly effective, noninvasive biomarkers for ESCC diagnosis.

Exposure to acidic gastric content due to malfunction of lower esophageal sphincter leads to acute reflux esophagitis (RE) leading to disruption of esophageal epithelial cells. Carbon monoxide (CO) produced by heme oxygenase (HMOX) activity or released from its donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) was reported to protect gastric mucosa against acid-dependent non-steroidal anti-inflammatory drug-induced damage. Thus, we aimed to investigate if CO affects RE-induced esophageal epithelium lesions development. RE induced in Wistar rats by the ligation of a junction between pylorus and forestomach were pretreated i.g. with vehicle CORM-2; RuCl 3 ; zinc protoporphyrin IX, or hemin. CORM-2 was combined with NG-nitro-L-arginine (L-NNA), indomethacin, capsazepine, or capsaicin-induced sensory nerve ablation. Esophageal lesion score (ELS), esophageal blood flow (EBF), and mucus production were determined by planimetry, laser flowmetry, histology. Esophageal Nrf-2, HMOXs, COXs, NOSs, TNF-α and its receptor, IL-1 family and IL-1 receptor antagonist (RA), NF-κB, HIF-1α, annexin-A1, suppressor of cytokine signaling (SOCS3), TRPV1, c-Jun, c-Fos mRNA/protein expressions, PGE 2 , 8-hydroxy-deoxyguanozine (8-OHdG) and serum COHb, TGF-β1, TGF-β2, IL-1β, and IL-6 content were assessed by PCR, immunoblotting, immunohistochemistry, gas chromatography, ELISA or Luminex platform. Hemin or CORM-2 alone or combined with L-NNA or indomethacin decreased ELS. Capsazepine or capsaicin-induced denervation reversed CORM-2 effects. COHb blood content, esophageal HMOX-1, Nrf-2, TRPV1 protein, annexin-A1, HIF-1α, IL-1 family, NF-κB, c-Jun, c-Fos, SOCS3 mRNA expressions, and 8-OHdG levels were elevated while PGE 2 concentration was decreased after RE. CO donor-maintained elevated mucosal TRPV1 protein, HIF-1 α, annexin-A1, IL-1RA, SOCS3 mRNA expression, or TGF-β serum content, decreasing 8-OHdG level, and particular inflammatory markers expression/concentration. CORM-2 and Nrf-2/HMOX-1/CO pathway prevent esophageal mucosa against RE-induced lesions, DNA oxidation, and inflammatory response involving HIF-1α, annexin-A1, SOCS3, IL-1RA, TGF-β-modulated pathways. Esophagoprotective and hyperemic CO effects are in part mediated by afferent sensory neurons and TRPV1 receptors activity with questionable COX/PGE 2 or NO/NOS systems involvement., Competing Interests: None declared

Background: This study aims to provide guidance for clinical work through analysis of the clinical characteristics, endoscopic and pathological manifestations, diagnosis, and treatment of an 18-day-old neonate with exfoliative esophagitis., Case Presentation: The patient presented with vomiting but the parents did not pay too much attention. The pathological report revealed numerous fibrinous exudative necrotic, and inflammatory cells, as well as a small amount of squamous epithelium. Furthermore, milk allergy factors were considered. Conservative treatments, such as fasting, acid suppression, mucosal protection, parenteral nutrition, and the replacement of anti-allergic milk powder were given. Thereafter, endoscopic examination revealed that the patient returned to normal, and was discharged after 21 days., Conclusions: Exfoliative esophagitis has multiple causes; and has characteristic clinical and endoscopic manifestations. Endoscopic examination after 18 days presentation and conservative therapy revealed that the esophagus had returned to a normal appearance and the patient was discharged. Following discharge, the parents were advised to feed the patient ALFERE powder. Attention should be given to the timely detection of complications and corresponding treatment.

The patient was a 76-year-old woman who had noticed slight difficulty in swallowing in the 3 years prior to this presentation. Her dysphagia progressed while she was hospitalized following cervical cancer surgery. Esophagogastroduodenoscopy and an esophagram showed circumferential erosion and a stricture of the thoracic esophagus. Esophageal resection was performed; the resected specimens showed a stricture and wall thickening. Histologically, transmural hyperplasia, which consisted of inflammatory granulation tissue with the abundant infiltration of IgG4-positive plasma cells and lymphocytes, was observed. The patient was diagnosed with probable IgG4-related disease. IgG4-related esophageal disease presenting as esophageal lesions alone is a very rare condition.

Aim: Metabolic profiling was performed on plasma samples obtained prior to and during radiation therapy (RT) for locally advanced lung cancer to identify metabolites predictive of RT-induced esophagitis., Patients and Methods: Patients received cisplatin/etoposide with RT as part of a prospective dose-escalation study (n=24). Plasma samples were collected at baseline, weeks 2 and 5 during RT, and 6 weeks post-RT. Metabolites were measured by ultrahigh-performance liquid chromatography-tandem mass spectroscopy at each time-point. Metabolite concentrations were compared between patients developing grade 0-1 and those with grade 2 or more esophagitis., Results: At baseline, 23 metabolites differed significantly (p<0.05) between patients with grade 0-1 esophagitis and those with grade 2 or esophagitis. Sixty-seven metabolites were different at week 2. None reached statistical significance (q<0.05) after corrections for multiple comparisons. On random forest modeling, the predictive accuracy of the metabolite data was 33% at baseline and 50% at 2 weeks., Conclusion: No individual metabolite or group of metabolites was predictive of acute RT-induced esophagitis., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined esophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients., Competing Interests: The authors declare no conflicts of interest.

Non-erosive esophagitis is a chronic inflammatory condition of the esophagus and is a form of gastroesophageal reflux disease. There are limited treatment options for non-erosive esophagitis, and it often progresses to Barrett's esophagus and esophageal carcinoma. Hydrogen sulfide has been demonstrated to be a critical mediator of gastric and intestinal mucosal protection and repair. However, roles for H2S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H2S in rat models of non-erosive esophagitis. Mild- and moderate-severity non-erosive esophagitis was induced in rats through supplementation of drinking water with fructose, plus or minus exposure to water-immersion stress. The effects of inhibitors of H2S synthesis or of an H2S donor on severity of esophagitis was then examined, along with changes in serum levels of a pro- and an anti-inflammatory cytokine (IL-17 and IL-10, respectively). Exposure to water-immersion stress after consumption of the fructose-supplemented water for 28 days resulted in submucosal esophageal edema and neutrophil infiltration and the development of lesions in the muscular lamina and basal cell hyperplasia. Inhibition of H2S synthesis resulted in significant exacerbation of inflammation and injury. Serum levels of IL-17 were significantly elevated, while serum IL-10 levels were reduced. Treatment with an H2S donor significantly reduced the severity of esophageal injury and inflammation and normalized the serum cytokine levels. The rat models used in this study provide novel tools for studying non-erosive esophagitis with a range of severity. H2S contributes significantly to mucosal defence in the esophagus, and H2S donors may have therapeutic value in treating esophageal inflammation and injury.

Objective: To investigate the effects of Zhuyeshigao granule (ZSG) on tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-2, IL-6, and IL-8 in rats with radiation esophagitis., Methods: Fifty Wistar rats were randomly divided into five groups (10 rats in each group): control (without radiation), saline-treated, and low, medium, and high-dose ISG-treated groups. Rats were given normal saline (10 mL/kg) or 1.15, 2.3, or 4.6 g/kg ZSG by intragastric administration once a day for 7 days. A rat model of radiation esophagitis was established by local irradiation of Co60 (490.25 cGy/min, totaling 30 Gy). The administration of ZSG was continued for another 7 days and on the 7th day post-irradiation, inferior vena cava blood was collected. The serum was separated, and TNF-alpha, IL-1, IL-2, IL-6, and IL-8 protein levels were determined., Results: Inflammatory response factors were found in the serum of each group. However, levels in ZSG-treated groups were significantly lower than in the saline-treated group (P < 0.05)., Conclusion: ZSG may prevent the development of radiation esophagitis, perhaps by inhibiting the generation and release of the inflammatory response factors TNF-alpha, IL-1, IL-2, IL-6, and IL-8.

Introduction: We hypothesized that radiation-induced thoracic toxicity (RITT) of the lung, esophagus and pericardium share a similar mechanism, and aimed to examine whether genetic variation of transforming growth factor-beta1 (TGFβ1), tissue plasminogen activator (tPA) and angiotensin converting enzyme (ACE), are associated with RITT in patients with non-small-cell lung cancer (NSCLC)., Methods: Patients with stage I-III NSCLC were enrolled and received radiotherapy (RT). Blood samples were obtained pre-RT and at 4 to 5 weeks during RT, and plasma TGF-β1 was measured using an enzyme-linked immunosorbent assay. The DNA samples extracted from blood pre-RT were analyzed for the following frequent genetic variations: TGFβ1 509C/T, tPA -7351 C/T, and ACE I/D. RITT score was defined as the sum of radiation-induced toxicity grades in esophagus, lung, and pericardium., Results: Seventy-six NSCLC patients receiving definitive RT were enrolled. Patients with TGFβ1 509CC had higher mean grade of esophagitis (1.4 ± 0.2 versus 0.8 ± 0.2, p = 0.019) and RITT score (2.6 ± 0.3 versus 1.6 ± 0.3, p = 0.009) than T allele carriers. Although no significant relationship was observed between RITT and the tPA or ACE variants individually, patients with any high-risk alleles (tPA CC or ACE D or TGFβ1 509CC) had significantly higher grade of developing combined RITT (p < 0.001). Patients with TGFβ1 509CC had greater increase of plasma TGF β1 levels at 4 to 5 weeks during RT than T allele carriers did (CC 1.2 ± 0.2 versus T 0.7 ± 0.1, p = 0.047)., Conclusion: This exploratory study demonstrated that sensitivity of radiation toxicity may be determined by genomic factors associated with TGFβ1 and genes involved in TGFβ1 pathway.

Context: Although the healthy esophageal mucosa contains no eosinophils, eosinophilic infiltration is observed in 2 major clinicopathologic settings: gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EE). The prevalence of EE is increasing in many countries, and this increase seems only partly to be due to a better awareness of the pathology, following the relatively recent description of EE. Gastroesophageal reflux disease and EE represent 2 entities that do not respond to the same treatment modalities and, thus, need to be distinguished. However, diagnostic criteria of EE have been defined arbitrarily, and the more recent articles tend to prove that the overlap with GERD is probably greater than initially believed, leading the authors to advise strict exclusion of GERD before considering the diagnosis of EE., Objectives: To provide pathologists with the currently proposed histologic criteria of GERD and EE, to stress the need to combine these criteria with clinical data and endoscopic findings, and to outline the remaining controversies., Data Sources: This review is based on selected articles identified by a PubMed (US National Library of Medicine, Bethesda, Maryland) search of the literature in English for GERD and EE, a recent review by the American Gastroenterological Association (Bethesda), the Proceedings of the First International Gastrointestinal Eosinophil Research Symposium, and the authors' experience., Conclusion: Proper identification of the etiology of eosinophilic infiltration of the esophagus allows accurate medical or surgical treatment and follow-up. Eosinophilic esophagitis and GERD diagnoses require integration of the histologic findings with the clinical and endoscopic data.

Background: Eosinophilic oesophagitis is thought to be an isolated oesophageal disease associated with biopsy-verified eosinophilia of the squamous cell epithelium of the oesophagus. Food- or aeroallergens have been suggested to be the cause of eosinophilic oesophagitis; however, as these allergens pass through the pharynx sharing the same squamous cell epithelium, eosinophilic infiltration could be expected also here. Whether this is true or not has hitherto not been clarified., Aim: To find out whether eosinophilia is present also within the pharyngeal epithelium in patients with eosinophilic oesophagitis., Methods: In all, 10 patients (median age 34, range 15-70) with biopsy-verified eosinophilic oesophagitis [peak count >20 eosinophils per high power field (hpf)] were biopsied also in the pharynx. The biopsies underwent histopathological examination and at each level, the peak number of eosinophils per hpf was counted., Results: None of the patients examined was found to have eosinophilia within the squamous cell epithelium of the pharynx (median peak count 0, range 0-1)., Conclusions: The pronounced eosinophilic infiltration in eosinophilic oesophagitis appears to be an isolated oesophageal phenomenon not shared by the adjoining organ sites and in particular, not by the pharynx. This may have implications for future research.

Background & Aims: Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia., Methods: A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined., Results: AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/muL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE., Conclusions: These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.

Background: The finding of an eosinophilic infiltration of the oesophageal epithelium has long been thought to be a result of gastro-oesophageal reflux disease. The association between this finding, an abnormal endoscopic appearance to the oesophagus with ridges and furrows in the oesophagus, and an association with recurrent food impactions in young men has also been described. It was first proposed that this was a distinct clinicopathological syndrome in 1993. Since that series, there have been increasing reports in the literature., Aims and Methods: This retrospective case series describes eight patients with eosinophilic oesophagitis. The mode of presentation, history, endoscopic findings, and histopathology of this condition are discussed. The first of these cases is described to illustrate the features of this condition, the salient features from the remaining cases are presented in tabular form., Conclusions: The syndrome of eosinophilic oesophagitis is considered a rare cause of dysphagia, however we report eight recent presentations to our general gastroenterological practice in Wellington, New Zealand and propose that it may be an important cause for dysphagia where no diagnosis has been forthcoming.

Background: Dietary questionnaire studies have suggested that patients with oesophageal adenocarcinoma are deficient in antioxidants. It is not known whether the same holds true for patients with the precursor lesion, Barrett's oesophagus., Aims: To evaluate the hypothesis that patients with Barrett's oesophagus are deficient in antioxidants compared with patients without evidence of Barrett's oesophagus., Patients and Methods: Plasma antioxidant profiles (copper, selenium, zinc; vitamins A, C, and E; carotenoids) were determined for patients with Barrett's oesophagus (n = 36), patients with erosive oesophagitis (n = 32), and patient controls (n = 35)., Results: Patients with Barrett's oesophagus had significantly lower plasma concentrations of selenium, vitamin C, beta cryptoxanthine, and xanthophyll compared with the other groups., Conclusions: This study confirms the hypothesis that patients with Barrett's oesophagus are deficient in certain antioxidants.

Aims: To investigate the efficacy of daily maintenance treatment with omeprazole 10 mg in reducing the relapse rate of healed erosive oesophagitis., Methods: Three hundred patients with erosive oesophagitis (grade 2 or greater) received omeprazole 20 mg daily for 12 weeks, followed by 40 mg daily for a further 12 weeks if required. After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse the treatment cycle was repeated., Results: The cumulative healing rate at 12 weeks in the initial healing period was 95%, and 96% and 98% on rehealing courses after relapse in the first and second maintenance periods respectively. After 12 weeks of treatment, 98% of patients were free from heartburn and 97% were free of all reflux related symptoms. Relapse in the subgroup of patients who relapsed in both maintenance periods was infrequent on omeprazole 20 mg daily: only 9% at two years. Gastrin concentrations rose above normal in one third of patients. One patient had linear hyperplasia of endocrine cells and another had micronodular hyperplasia. There were no side effects definitely attributable to omeprazole., Conclusion: Maintenance treatment with omeprazole 10 mg daily keeps about 60% of patients with erosive oesophagitis in prolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20 mg daily.

Background: Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man., Aims: To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment., Methods: Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment., Results: In the patients randomised to anti-H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26-86) at initial presentation and increased to 64 ng/l (range 29-271) after seven months omeprazole, representing a median increase of 68% (p < 0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17-226) and was unchanged after seven months omeprazole at 38 ng/l (range 17-95)., Conclusion: Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long-term proton pump inhibitor treatment.

Forty-two patients with peptic ulceration of the duodenum, stomach or oesophagus, who had not responded to 3 or more months of high-dose treatment with ranitidine (450 or 600 mg/day), were treated with oral lansoprazole at 30-60 mg daily. In 40 patients (95.2%) the ulcers healed within 2-12 weeks. In the remaining 2 patients healing took several months but eventually all ulcers healed. After healing, 40 patients underwent long-term maintenance treatment with 30-60 mg lansoprazole daily for 1-3 years (continuing). During maintenance therapy with lansoprazole, no endoscopically verified relapses occurred when the drug was taken regularly. In 1 patient treatment had to be discontinued because of a drug-related colitis that disappeared soon after treatment had been stopped. There were no significant changes in routine laboratory tests in any patient. Basal serum gastrin concentrations, which were already elevated by the previous high-dose ranitidine treatment (125 +/- 25 pg/ml), rose to four times the normal values after 4 weeks of treatment with lansoprazole (255 +/- 65 pg/ml). Thereafter no further increases in basal serum gastrin concentrations were observed, even after 3 years of administration. The volume density of argyrophilic cells in the oxyntic mucosa increased slightly during lansoprazole treatment; until now no dysplasia of the enterochromaffin-like cells has been observed. In conclusion, 30-60 mg lansoprazole daily healed ranitidine-resistant peptic ulcers, and subsequent maintenance therapy with 30-60 mg lansoprazole daily was found to be highly effective and safe over the time observed.

To assess the effect of cimetidine and ranitidine on high density lipoprotein (HDL) cholesterol concentration two groups of eight patients with duodenal ulcer or oesophagitis matched for age, sex, and cigarette consumption were given either cimetidine 1 g daily or ranitidine 300 mg daily for one month. There was no significant change in the cholesterol content of HDL and its subfraction HDL3 after treatment with ranitidine or cimetidine, or in the cholesterol content of the subfraction HDL2 after treatment with ranitidine; the HDL2 cholesterol concentration was, however, significantly increased after treatment with cimetidine. Further studies are being undertaken to establish the mechanism of this effect.