Project description:BACKGROUND: Intestinal metaplastic mucosa in Barrett's oesophagus can be replaced by squamous epithelium after mucosal thermal ablation associated with acid suppression therapy. AIMS: To assess whether restoration of squamous epithelium can be obtained after ablation of Barrett's oesophagus using argon plasma coagulation (APC) associated with proton pump inhibitor (PPI) therapy. METHODS: Thirty one patients with Barrett's oesophagus received APC. Omeprazole (40 mg/day) was given from the first APC application to one month after completion of the treatment, then given symptomatically. Twenty four hour pH-metry was performed during endotherapy. RESULTS: Complete re-epithelialisation was visualised at endoscopy in 25/31 patients (81%) after a mean number of 2.4 APC sessions (range 1-4). Only partial squamous re-epithelialisation was observed in three patients and three others had no eradication. At histological assessment, eradication of Barrett's oesophagus was only confirmed in 19/31 patients (61%) due to the presence of a few residual Barrett's glands under the new squamous epithelium. Complete eradication was related to a Barrett's oesophagus segment length of less than 4 cm and the absence of circumferential extension but not to the normalisation of oesophageal acid exposure under PPI therapy. Seventeen patients with apparently complete endoscopic and histological eradication of Barrett's oesophagus were re-evaluated at one year; eight (47%) disclosed relapsing islands of Barrett metaplasia despite continuous omeprazole therapy (10-40 mg/day). CONCLUSIONS: APC combined with 40 mg omeprazole daily can eradicate Barrett's mucosa with apparent squamous re-epithelialisation in the majority of patients even in the absence of normalisation of oesophageal acid exposure. However, one year after endotherapy for Barrett's oesophagus, relapse is frequent but limited in extent.
Project description:Background and study aims Argon plasma coagulation (APC) is an effective and safe modality for many gastrointestinal conditions requiring hemostasis and/or ablation. However, it can be quite costly. A potentially more cost-effective alternative is snare-tip spray coagulation (SC). This study aimed to determine whether SC would be a safe and effective alternative to APC using an ex-vivo model. Methods Using two resected porcine stomach, 36 randomized gastric areas were ablated for 2 seconds with either APC at 1.0 L/min 20 W (APC20) and 1.4 L/min 40 W (APC40) or SC with Effect 2 60 W (SC60) and 80 W (SC80) from 3 mm. Extent of tissue injury was then analyzed histopathologically. Results The mean coagulation depth was 790 ± 159 µm and 825 ± 467 µm for SC60 (n = 9) and SC80 (n = 8), respectively. This was compared to 539 ± 151 µm for APC20 (n = 8) and 779 ± 267 µm for APC40 (n = 9). Mean difference (MD) in coagulation depth between SC60 and APC40 was 12 µm (95 % confidence interval [CI], -191 to 214 µm; P = 0.91) and was 47 µm (95 %CI, -162 to 255 µm; P = 0.81) between SC80 and APC40. There was a greater depth of injury with APC40 (MD, 240 µm; 95 %CI, 62 to 418 µm; P = 0.04) and with SC60 (MD, 252 µm; 95 %CI, 141 to 362 µm; P = 0.004) when compared to APC20. Mean cross-sectional area of coagulation was 2.39 ± 0.852 mm² for SC60 and 2.54 ± 1.83 mm² for SC80 compared to 1.22 ± 0.569 mm² for APC20 and 1.99 ± 0.769 mm² for APC40. Seventy-eight percent reached the muscularis mucosa (MM) and 11 % the submucosa in the SC60 group compared to 50 % and 38 % in SC80 and 56 % and 11 % in APC40, respectively. Thirty-eight percent of APC20 specimens reached the MM. The muscularis propria was unaffected. Conclusions This small ex-vivo study suggests that SC60 and SC80 may be safe alternatives to APC40 with comparable coagulation depths and area effects.
Project description:Barrett's esophagus transcriptome was analysed and compared with Barrett's esophagus primary cell culture and esophageal adenocarcinoma. Keywords: SAGE analysis to compare tissues Barrett's esophagus biopsy was taken from 1 male metaplastic Barrett's esophagus patient. Barrett's esophagus primary cell culture was cultures from a biopsy taken from a Barrett's esophagus patient and cultured for about 4 to 5 weeks. Esophageal adenocarcinoma was taken from a patient known to have cancer and previously Barrett's esophagus
Project description:Barrett's esophagus transcriptome was analysed and compared with Barrett's esophagus primary cell culture and esophageal adenocarcinoma. Keywords: SAGE analysis to compare tissues
Project description:Barrett's esophagus (BE) increases the risk for development of esophageal adenocarcinoma. Because of the rapid rise in incidence of esophageal adenocarcinoma, screening for BE with subsequent surveillance when found has been proposed as a method of early detection. Sedated endoscopy, however, is too expensive for wide spread screening. As a result, other techniques including unsedated transnasal esophagoscopy and capsule esophagoscopy have been proposed to expand screening programs.
Project description:BackgroundSelf-expandable metal stents (SEMSs) are the main palliative modality used in inoperable oesophageal cancer. Other palliative modalities, including argon plasma coagulation (APC), have also been used.ObjectiveThe purpose of this study was to assess the relative efficacy of SEMS and APC regarding the survival of patients with inoperable oesophageal cancer, not receiving chemo/radiotherapy.MethodsSingle centre, retrospective analysis of all patients (n = 228) with inoperable oesophageal cancer between January 2000 and July 2014, not receiving chemo-radiotherapy, treated with SEMS (n = 160) or APC (n = 68) as primary palliation modalities. Cox regression analysis was performed to identify individual factors affecting survival and Kaplan-Meier curves were created for patients treated with APC and SEMS for stage III and IV disease. Survival intervals were compared by the log-rank test.ResultsType of treatment was the only statistically significant factor affecting survival, after disease stage stratification (hazard ratio (HR): 1.36, 95% confidence interval (CI): 1.13-1.65 of SEMS over APC, p: 0.002). Median survival for patients treated with APC and SEMS was 257 (interquartile range (IQR): 414, 124) and 151 (IQR: 241, 61) days respectively in stage III disease. It was 135 (IQR: 238, 43) and 70 (IQR: 148, 32) days respectively in stage IV disease. Both differences were statistically significant (p = 0.02 and 0.05 respectively).ConclusionsAPC is a promising palliation modality in inoperable oesophageal cancer, when patients are not candidates for chemo-radiotherapy. A randomized controlled trial will be needed to confirm those results.
Project description:As the premalignant lesion of human esophageal adenocarcinoma (EAC), Barrett's esophagus (BE) is characterized by intestinal metaplasia in the normal esophagus (NE). Gene expression profiling with microarray and serial analysis of gene expression (SAGE) may help us understand the potential molecular mechanism of human BE.We analyzed three microarray datasets (two cDNA arrays and one oligonucleotide array) and one SAGE dataset with statistical tools, significance analysis of microarrays (SAM) and SAGE(Poisson), to identify individual genes differentially expressed in BE. Gene set enrichment analysis (GSEA) was used to identify a priori defined sets of genes that were differentially expressed. These gene sets were grouped according to either certain signaling pathways (GSEA curated), or the presence of consensus binding sequences of known transcription factors (GSEA motif). Immunohistochemical staining (IHC) was used to validate differential gene expression.Both SAM and SAGE(Poisson) identified 68 differentially expressed genes (55 BE genes and 13 NE genes) with an arbitrary cutoff ratio (> or =4-fold). With IHC on matched pairs of NE and BE tissues from 6 patients, these genes were grouped into 6 categories: category I (25 genes only expressed in BE), category II (5 genes only expressed in NE), category III (8 genes expressed more in BE than in NE), and category IV (2 genes expressed more in NE than in BE). Differential expression of the remaining genes was not confirmed by IHC either due to false discovery (category V), or lack of proper antibodies (category VI). Besides individual genes, the TGFbeta pathway and several transcription factors (CDX2, HNF1, and HNF4) were identified by GSEA as enriched pathways and motifs in BE. Apart from 9 target genes known to be up-regulated in BE, IHC staining confirmed up-regulation of 19 additional CDX1 and CDX2 target genes in BE.Our data suggested an important role of CDX1 and CDX2 in the development of BE. The IHC-confirmed gene list will lead to future studies on the molecular mechanism of BE.
Project description:Risk factors for Barrett's esophagus include gastroesophageal reflux disease (GERD) symptoms, age, abdominal obesity, and tobacco use. We aimed to develop a tool using these factors to predict the presence of Barrett's esophagus.Male colorectal cancer (CRC) screenees were recruited to undergo upper endoscopy, identifying newly diagnosed cases of Barrett's esophagus. Logistic regression models predicting Barrett's esophagus using GERD symptoms alone and together with abdominal obesity, tobacco use, and age were compared.Barrett's esophagus was found in 70 (8.5%) of 822 CRC screenees. Mutually adjusting for other covariates, Barrett's esophagus was associated with weekly GERD (odds ratio (OR)=2.33, 95% confidence interval (CI)=1.34, 4.05), age (OR per 10 years=1.53, 95% CI=1.05, 2.25), waist-to-hip ratio (OR per 0.10=1.44, 95% CI=0.898, 2.32) and pack-years of cigarette use (OR per 10 pack-years=1.09, 95% CI=1.04, 1.14). A model including those four factors had a greater area under the receiver operating characteristics curve than did a model based on GERD frequency and duration alone (0.72 vs. 0.61, P<0.001), and it had a net reclassification improvement index of 19-25%.The prevalence of Barrett's esophagus was substantial in our population of older overweight men. A model based on GERD, age, abdominal obesity, and cigarette use more accurately classified the presence of Barrett's esophagus than did a model based on GERD alone. Following validation of the tool in another population, its use in clinical practice might improve the efficiency of screening for Barrett's esophagus.
Project description:Patients with Barrett's esophagus have a significantly increased risk of esophageal adenocarcinoma, 40-125 times higher than the general population. Since only a small fraction of Barrett's esophagus patients will actually progress to esophageal adenocarcinoma, there is a need to develop markers that may accurately predict which patients with Barrett's esophagus are likely to have aggressive disease and progress to cancer versus patients who will remain histologically stable and have a benign course. This would allow for better risk stratification of patients with Barrett's esophagus in order to target aggressive surveillance and intervention towards only those patients at highest risk for neoplastic progression. Predictive biomarkers may thus have significant clinical utility in the management of Barrett's esophagus patients. The detection of dysplasia in esophageal biopsies is currently the only standard method used in clinical practice as a marker for increased risk of cancer. However, dysplasia has not been a accurate or reliable marker for predicting malignant progression and suffers from poor interobserver agreement among pathologists and sampling error. A multitude of potential biomarkers have been studied over the years. It is likely that the best model for predicting progression to esophageal adenocarcinoma in Barrett's esophagus patients will ultimately involve a combination of biomarkers, dysplasia grade and other pathological characteristics, as well as clinical and demographic attributes. In this review, we will discuss the most promising biomarkers that have been studied thus far.
Project description:Esophageal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Western countries. The incidences of esophageal adenocarcinoma and its precursor Barrett's esophagus have increased substantially in the last four decades. Current care guidelines recommend that endoscopy be used for the early detection and monitoring of patients with Barrett's esophagus; however, the efficacy of this approach is unclear. To prevent the increasing morbidity and mortality from esophageal adenocarcinoma, there is a tremendous need for early detection and surveillance biomarker assays that are accurate, low-cost, and clinically feasible to implement. The last decade has seen remarkable advances in the development of minimally invasive molecular biomarkers, an effort led in large part by the Early Detection Research Network (EDRN). Advances in multi-omics analysis, the development of swallowable cytology collection devices, and emerging technology have led to promising assays that are likely to be implemented into clinical care in the next decade. In this review, an updated overview of the molecular pathology of Barrett's esophagus and esophageal adenocarcinoma and emerging molecular biomarker assays, as well as the role of EDRN in biomarker discovery and validation, will be discussed.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."