Psychosocial factors and their association with reflux oesophagitis,Barrett’s oesophagus and oesophageal adenocarcinoma

AIM:To investigate the role of psychological characteristics as risk factors for oesophageal adenocarcinoma(OAC),as well as the reflux-mediated precursor pathway.METHODS:An all-Ireland population-based case-control study recruited 230 reflux oesophagitis(RO),224 Barrett’s oesophagus(BO) and 227 OAC patients and 260 controls.Each case/control group completed measures of stress,depression,self-efficacy,self-esteem,repression and social support.A comparative analysis was undertaken using polytomous logistic regression adjusted for potential confounders.RESULTS:Compared to controls,OAC patients were almost half as likely to report high stress levels over their lifetime(P = 0.010,OR 0.51;95%CI:0.29-0.90)and 36% less likely to report having experienced depression(OR 0.64;95%CI:0.42-0.98).RO patients reported significantly higher stress than controls particularly during middle-and senior-years(P for trends < 0.001).RO patients were 37% less likely to report having been highly emotionally repressed(OR 0.63;95%CI:0.41-0.95).All case groups(OAC,RO and BO) were more likely than controls to report having had substantial amounts of social support(OR 2.84;95%CI:1.63-4.97;OR 1.97;95%CI:1.13-3.44 and OR 1.83;95%CI:1.03-3.24,respectively).CONCLUSION:The improved psychological profile of OAC patients may be explained by response shift.The role of psychological factors in the development of OAC requires further investigation.     

Screening for Barrett’s oesophagus with oesophageal capsule endoscopy in first-degree relatives of patients affected by Barrett’s oesophagus: Results of a pilot study

Background and study aimsBarrett’s oesophagus (BE) is one of the complications of gastro-oesophageal reflux disease (GERD). Oesophageal capsule endoscopy (ECE) has been proposed as a non-invasive investigation of oesophageal pathology. The aims were to evaluate the diagnostic yield of ECE in first-degree relatives of patients with BE and reflux symptoms and to assess prospectively the prevalence of BE in these conditions.Patients and methodsInclusion criteria were familial history of at least one first-degree relative with BE and typical reflux syndrome. Patients underwent ECE followed by oesophagogastroduodenoscopy (EGD). The ECE findings were compared with those during EGD.ResultsBetween February and October 2009, 18 patients were enrolled. Oesophagitis and endoscopically suspected oesophageal metaplasia (ESEM) were present, at ECE, in 7 and 11 patients, respectively. Intestinal metaplasia was histologically confirmed in eight patients. Sensitivity and specificity of ECE were, respectively, 86% and 91%, for oesophagitis, and 100% and 70% for ESEM; positive predictive value (PPV) and negative predictive value (NPV) were 86% and 91%, respectively, for oesophagitis and 73% and 100%, respectively, for ESEM. Prevalence of BE was 44%.ConclusionECE showed an optimal NPV for BE detection. Pending confirmation of these results, ECE could be proposed as a screening test in symptomatic relatives of patients with BE.     

Management controversies in Barrett’s oesophagus

The management of Barrett’s oesophagus and associated neoplasia has evolved considerably in recent years. Modern endoscopic strategies including endoscopic resection and mucosal ablation can eradicate dysplastic Barrett’s and prevent progression to invasive oesophageal cancer. However, several aspects of Barrett’s management remain controversial including the stage in the disease process at which to intervene, and the choice of endoscopic or surgical therapy. A review of articles pertaining to the management of Barrett’s oesophagus with or without associated neoplasia, was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, Embase and Cochrane databases were searched to identify literature relevant to eight pre-defined areas of clinical controversy. The following search terms were used: Barrett’s oesophagus; dysplasia; intramucosal carcinoma; endotherapy; endoscopic resection; ablation; oesophagectomy. A significant body of evidence exists to support early endoscopic therapy for high-grade dysplasia (HGD). Although not supported by randomised controlled trial evidence, endoscopic therapy is now favoured ahead of oesophagectomy for most patients with HGD. Focal intramucosal (T1a) carcinomas can be managed effectively using endoscopic and surgical therapy, however surgery should be considered the first line therapy where there is submucosal invasion (T1b). Treatment of low grade dysplasia is not supported at present due to widespread over-reporting of the disease. The role of surveillance endoscopy in non-dysplastic Barrett’s remains controversial.     

Risk factors for Barrett＇s oesophagus and oesophageal adenocarcinoma： Results from the FINBAR study

AIM:To investigate risk factors associated with Barrett's oesophagus and oesophageal adenocarcinoma.METHODS:This all-Ireland population-based case-control study recruited 224 Barrett's oesophagus patients,227 oesophageal adenocarcinoma patients and 260 controls.All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors.RESULTS:Gastro-oesophageal reflux was associated with Barrett's [OR 12.0(95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48(95% CI 2.25-5.41)].Oesophageal adenocarcinoma patients were more likely than controls to be ex-or current smokers [OR 1.72(95% CI 1.06-2.81)and OR 4.84(95% CI 2.72-8.61)respectively] and to have a high body mass index [OR 2.69(95% CI 1.62-4.46)].No significant associations were observed between these risk factors and Barrett's oesophagus.Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50(95% CI 0.30-0.86)].CONCLUSION:A high body mass index,a diet low in fruit and cigarette smoking may be involved in the progression from Barrett's oesophagus to oesophageal adenocarcinoma.     

Barrett's oesophagus and oesophageal adenocarcinoma: how does acid interfere with cell proliferation and differentiation?

Acid, a principal component of gastro-oesophageal refluxate, may contribute to the development and malignant progression of Barrett's oesophagus. Oesophageal pH monitoring studies have demonstrated that patients with Barrett's oesophagus have severe and chronic acid reflux. However, there is overlap between the amount of acid exposure in patients with oesophagitis compared with patients with Barrett's oesophagus. This suggests that factors other than acid may be important in the aberrant oesophageal cell differentiation process that leads to the development of the metaplastic Barrett's mucosa. The other factors important in the aetiology of Barrett's oesophagus are poorly understood but probably include both genetic and environmental factors.     

Treatment of Barrett’s esophagus with high-grade dysplasia and intramucosal adenocarcinoma

High-grade dysplasia and intramucosal adenocarcinoma are premalignant and malignant lesions of the esophagus. The incidence of lymphatic or systemic metastases is low and esophagectomy is curative in most patients. Until recently, complete removal of the neoplastic tissue was reliably accomplished with only esophagectomy. New technologies have been developed that allow endoscopic mucosal resection and ablation with preservation of the esophagus for these lesions. Optimal treatment of the patient requires consideration of not only the stage of the lesion but also the pathophysiology of the esophagus and the severity of the underlying reflux disease. Only with this approach can outcomes be optimized for both the dysplasia or cancer and the patient’s reflux disease and long-term quality of life. In this article, we summarize the experience from a surgical center’s perspective.     

Diagnosis and treatment of Barrett’s esophageal adenocarcinoma

In the last 30 years the incidence of esophageal adenocarcinoma has greatly increased in the United States and Europe, but not in Japan. Most adenocarcinomas arise in Barretts esophagus, an intestinal metaplasia with goblet cells. On endoscopy in Barretts esophagus, the red columnar epithelium extending upwards in the lower esophagus is easily seen, and biopsies confirm metaplasia. Patients with Barretts esophagus usually have severe esophageal reflux, a weak lower sphincter, and hiatus hernia. Medical or surgical treatment for reflux can relieve symptoms, but the Barretts esophagus and increased cancer risk remain. About 5% of Barretts patients die from esophageal cancer. In Barretts, low-grade then high-grade dysplasia usually precede invasive cancer. Endoscopic biopsy surveillance of patients with Barretts esophagus can detect malignancy at an early, curable stage. However, most cases of Barretts developing adenocarcinoma are still not found until advanced cancer has developed. As about 20% of adults in the United States have reflux symptoms weekly, and 5% of these have Barretts esophagus, population screening for Barretts esophagus would be a major effort. With no, or low-grade dysplasia, surveillance endoscopy is usually done. High-grade dysplasia or early adenocarcinoma is often managed by esophagectomy; endoscopic mucosal resection for selected cases is being evaluated. Five-year survival with later-stage adenocarcinomas following transthoracic or transhiatal resection is about 15%. Controlled trials indicate surgical results may be improved by preoperative chemotherapy and radiation. For palliation of dysphagia in nonoperation cases, stent placement or endoscopic laser debulking are used.     

Evaluation of nitric oxide synthase activity, nitric oxide, and homocysteine levels in patients with active Behcet’s disease

Behcet’s disease (BD) is a chronic, progressive disorder that affects many systems of the body including the eye. The aim of this study was to examine the effects of nitric oxide synthase activity (NOS), nitric oxide , and homocysteine (Hcy) levels in patients with active BD. Included in this study were 18 male BD patients and 16 male healthy volunteers as controls. Erythrocyte NOS activity, , erythrocyte sedimentation rate, serum C-reactive protein, and plasma Hcy values in the patients with BD were significantly higher than those of the control group. Our results show that these parameters play a major role in the inflammatory reactions observed in BD.     

Evaluation of depression, quality of life and body image in patients with Cushing’s disease

The aim of this study was to evaluate patients with Cushing’s disease (CD) who had undergone transsphenoidal surgery in terms of depression, quality of life (QoL), and perception of body image in comparison to healthy controls. Forty patients with CD and 40 healthy controls matched for demographic characteristics were included in the study. The subjects were evaluated with the Beck depression inventory (BDI), the health survey-short form (SF-36) and the multidimensional body-self relations questionnaire (MBSRQ). Subgroups of the patients with CD were formed on the basis of remission status and BDI scores. In this study, QoL in the general health category and body image were lower in the patients with CD than in the healthy subjects. However, no differences in depression scores were found between the two groups. When the CD group was evaluated according to remission rate, the mean BDI score was significantly higher in the CD patients without remission than in both the CD patients with remission and the healthy subjects (p = 0.04). However, the physical functioning, bodily pain and general health scores of the CD patients without remission on the SF-36 questionnaire were lower than in the CD patients in remission and the healthy subjects (p = 0.002, p = 0.04, p = 0.002, respectively). Fitness evaluation, health evaluation and body areas satisfaction scores of the MBSRQ were significantly different in the three groups (p = 0.003, p = 0.009 and p = 0.001, respectively). In this study, patients with CD were found to have lower QoL, lower body image perception and higher levels of depression compared to healthy controls, particularly if the disease is persistant despite surgery.     

MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma

Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellul...     

Gene expression in rats with Barrett＇s esophagus and esophageal adenocarcinoma induced by gastroduodenoesophageal reflux

AIM: To study the different gene expression profiles in rats with Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) induced by gastro-duodeno-esophageal reflux. METHODS: Esophagoduodenostomy was performed in 8-wk old Sprague-Dawley rats to induce gastro-duodeno-esophageal reflux, and a group of rats that received sham operation served as control. Esophageal epithelial pathological tissues were dissected and frozen in liquid nitrogen immediately. The expression profiles of 4 096 genes in EA and BE tissues were compared to normal esophagus epithelium in normal control (NC) by cDNA microarray. RESULTS: Four hundred and forty-eight genes in BE were more than three times different from those in NC, including 312 upregulated and 136 downregulated genes. Three hundred and seventy-seven genes in EA were more than three times different from those in NC, including 255 upregulated and 142 downregulated genes. Compared to BE, there were 122 upregulated and 156 downregulated genes in EA. In the present study, the interested genes were those involved in carcinogenesis. Among them, the upregulated genes included cathepsin C, aminopeptidase M, arachidonic acid epoxygenase, tryptophan-2,3-dioxygenase, ubiquitin-conjugating enzyme, cyclic GMP-stimulated phosphodiesterase, tissue inhibitor of metalloproteinase-1, betaine-homocysteine methyltra nsferase, lysozyme, complement 4b binding protein, complement 9 protein, insulin-like growth factor binding protein, UDP-glucuronosyltransferase, tissue inhibitor of metalloproteinase-3, aldolase B, retinoid X receptor gamma, carboxylesterase and testicular cell adhesion molecule 1. The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC, heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand. CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux may develop into BE and even EA gradually. The gene expression level is different between EA and BE, and may be related to the occurrence and progression of EA.     

Biomarkers in Barrett’s esophagus and esophageal adenocarcinoma:Predictors of progression and prognosis

Barrett’s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett’s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett’s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett’s esophagus and EA and to discuss what is required to move the field forward towards clinical application.     

Esophageal motility in Japanese patients with Barrett’s esophagus

Background The prevalence of gastroesophageal reflux disease has been increasing in Japan as it has in Western countries, but Barretts esophagus (BE) is less common in Japan than in Western countries. The aim of this study, therefore, was to investigate esophageal motility and clinical characteristics in Japanese patients with BE.Methods Ten patients with BE were compared with ten patients with mild reflux esophagitis (RE), ten patients with severe RE, and ten healthy subjects of comparable age and sex. The prevalence of Helicobacter pylori was investigated in the patients with BE. The intraluminal microtransducer method was used to test for esophageal motility. Basal lower esophageal sphincter (LES) pressure was assessed by the rapid pull-through method. The esophageal wave after ten repeated 5-ml water swallowings at 30-s intervals was measured at 3, 8, 13, and 18cm above the LES.Results The basal LES pressure, the amplitude of the esophageal wave at 3 and 8cm above the LES, and the frequency of primary peristalsis in the severe RE group and BE group were significantly lower than the values in the healthy subjects and the mild RE group. The amplitude of the esophageal wave 13cm above the LES in the BE group was significantly lower than that in the healthy subjects and the mild RE group. There was no difference between the severe RE group and the BE group in the basal LES pressure and the amplitude of the esophageal wave. The frequency of primary peristalsis in the BE group, however, was significantly lower than that in the severe RE group. Nine of the ten patients with BE were H. pylori-negative.Conclusions Our conclusions are that esophageal dysmotility in Japanese patients with BE represents an advanced stage of severe RE, and that most Japanese patients with BE are H. pylori-negative.     

E-cadherin expression in Barrett’s esophagus and esophageal carcinoma

Introduction

In multicellular organisms the development of adhesion bonds either among cells or among cells and components of the extracellular matrix is a crucial process. These interactions are mediated by molecules, named adhesion molecules. Their molecular and genetic structure, their biochemical role and their functional characteristics are nowadays clearly determined. At present, adhesion molecules embrace five categories: cadherins, integrins, immunoglobulin gene superfamily members, selectins and CD44. Cadherins are the most interesting group among all adhesion molecules, given the fact that at their presence all adhesion interactions may be continued, despite the potential absence of all of the remainder of the adhesion molecule groups. Cadherins apart from playing a crucial role in tissue architecture formation and maintenance in adult animals and humans, they play an equal importance role in tissue architecture alteration/distortion. This latter role is unambiguous nowadays and the most extensively studied paradigm occurs in carcinogenesis. E-cadherin down-regulation is a general phenomenon observed in many malignant lesions in humans including head and neck, esophageal, gastric, colorectal, pancreatic, primary liver, prostate, and bladder cancer, as well as in pre-malignant lesions including Barrett’s esophagus, and cervical intraepithelial neoplasia.

Materials and methods

Review article.

Conclusion

In this review we try to elucidate the expression of E-cadherin and related molecules in Barrett’s esophagus as well as in malignant lesions of the esophagus like adenocarcinoma and squamous cell carcinoma.     

Biochemical and immunohistochemical analysis of glycosaminoglycans in inflamed and non-inflamed intestinal mucosa of patients with Crohn’s disease

OBJECTIVES: Changes in extracellular matrix glycosaminoglycans (GAGs) of the intestinal mucosa have been associated with inflammatory bowel disease. The aim of the present study was to follow the changes in GAGs metabolism during the progression from non-inflamed to inflamed intestinal colon of patients with Crohn's disease (CD), using direct biochemical analysis and specific immunohistochemistry against chondroitin/dermatan sulfate and heparan sulfate. DESIGN AND METHODS: The content of GAGs from inflamed and non-inflamed colon of eight patients with active CD was estimated by uronic acid per dry weight of tissue and analyzed by agarose gel electrophoresis and ion-exchange chromatography. Intestinal sections were stained using antibodies against dermatan sulfate/chondroitin 4-sulfate (DS/CS), heparan sulfate (HS), and ICAM-1 (CD54), and analyzed by confocal microscopy. RESULTS: There was a reduction in the amount of GAGs in the non-inflamed colon of patients with CD. In the inflamed colon, HS, CS and DS showed increased concentrations compared with the non-inflamed colon. GAGs showed a diffuse distribution in the lamina propria and in the basement membrane of both inflamed and non-inflamed mucosa of patients with CD. CONCLUSION: We observed a marked reduction in GAGs with altered patterns of distribution in the non-inflamed colon of patients with CD. The increase in the synthesis of GAGs observed in the inflamed colon may be a compensatory mechanism for the restoration of the integrity of the intestinal mucosa.     

Magnification Endoscopy and Chromoendoscopy in Evaluation of Specialized Intestinal Metaplasia in Barrett’s Esophagus

Background  

Specialized intestinal metaplasia (SIM) in Barrett’s esophagus is a risk factor of esophageal adenocarcinoma. It often occurs focally and cannot be distinguished from surrounding columnar epithelium with conventional endoscopy.     

Characteristics of patients with columnar-lined Barrett＇s esophagus and risk factors for progression to esophageal adenocarcinoma

AIM: To determine the risk factors for the development of esophageal adenocarcinoma in these patients with columnar-lined esophagus (CLE). METHODS: Data collected retrospectively on 597 consecutive patients diagnosed at endoscopy and histology to have CLE at Leeds General Infirmary between 1984 and 1995 were analyzed. Factors evaluated included age, sex, length of columnar segment, smoking, and drinking habits, history of non-steroidal ingestion, presence of endoscopic esophagitis, ulceration or benign strictures and presence of Helicobacter pylori in esophageal biopsies. Univariate and multivariate analyses were performed to identify risk factors for the development of adenocarcinoma. RESULTS: Forty-four patients presented or developed esophageal adenocarcinoma during follow-up. Independent risk factors for the development of adenocarcinoma in patients with CLE were males (OR 5.12, 95%CI 2.04-12.84, P = 0.0005), and benign esophageal stricture (OR 4.37, 95%CI 2.02-9.45, P = 0.0002). Male subjects and patients who developed benign esophageal stricture constituted 86% (n = 38) of all patients who presented or developed esophageal adenocarcinoma. The presence of esophagitis was associated with a significant reduction in the development of esophageal carcinoma (OR 0.28, 95%CI 0.13-0.57, P = 0.0006). No other clinical characteristics differentiate between the non-malignant and malignant group. CONCLUSION: In patients with CLE, endoscopic surveillance for the early detection of adenocarcinoma may be restricted to male subjects, as well as patients who develop benign esophageal strictures.     

Proximal and distal esophageal sensitivity is decreased in patients with Barrett’s esophagus

AIM: To investigate sensations to multimodal pain stimulation in the metaplastic and normal parts of the esophagus in patients with Barrett’s esophagus (BE). METHODS: Fifteen patients with BE and 15 age-matched healthy volunteers were subjected to mechanical, thermal and electrical pain stimuli of the esophagus. Both the metaplastic part and the normal part (4 and 14 cm, respectively, above the esophago-gastric junction) were examined. At sensory thresholds the stimulation intensity, referred pain areas, an...