Barrett's Dysplasia Research Articles

Upper gastrointestinal cancers: Are all carcinomas truly carcinomas?

20 Background: Poorly differentiated cancer of the upper GI tract is a challenging diagnosis for the pathologist, who will rely on a positive cytokeratin immunostaining to confirm the epithelial origin of the tumor. Being confronted with a highly unusual case (a poorly differentiated esophageal “carcinoma” with immunophenotypic and genetic sarcoma-like features, arising in the background of high grade Barrett dysplasia), we retrospectively investigated whether other cancer cases displayed the same unusual features. Methods: 34 poorly differentiated GI cancers were selected based on availability of FFPE. All cases were investigated by (1) immunohistochemistry for selected carcinoma and sarcoma markers (prekeratin, NCAM, vimentin, CD99) and by (2) FISH for presence/absence of abnormalities of 2 genes, SYT and EWS, that are frequently rearranged in synovial and Ewing’s sarcoma respectively. Results: 6/34 cases displayed an aberrant immunophenotype, with expression of NCAM, vimentin, and/or CD99. FISH revealed a substantial number (9/34) of SYT and EWS related anomalies: 1 EWS rearrangements, 1 SYT rearrangements, 1 SYT and 1 EWS focal amplification, and 4 aneuploidies. While EWS and SYT are (mostly) fused to ERG or SSX1/2 in Ewing’s and synovial sarcoma respectively, these genes were found to be intact in our EWS and SYT rearranged cases. Conclusions: Our data show that SYT & EWS abnormalities are recurrently occurring in poorly differentiated GI cancers that are (mis?)diagnosed as carcinomas. While EWS rearrangement has previously been described in cancer types other than Ewing’s sarcoma, SYT rearrangement was so far thought to be exclusive to the diagnosis of synovial sarcoma. In addition, EWS/SYT abnormalities in our series seemed to target cancers that are at risk of not responding well to the conventional chemoradiotherapy regimen. Of interest, the one “carcinoma” patient that started this study went into complete remission after being administered a sarcoma targeted therapy. We also infer from our results that good histologic assessment of GI cancers is essential for clinical trials aiming at targeted therapy, as not all carcinomas may present true carcinomas.

Immunohistochemical assessment of NY-ESO-1 expression in esophageal adenocarcinoma resection specimens.

To assess NY-ESO-1 expression in a cohort of esophageal adenocarcinomas. A retrospective search of our tissue archive for esophageal resection specimens containing esophageal adenocarcinoma was performed, for cases which had previously been reported for diagnostic purposes, using the systematised nomenclature of human and veterinary medicine coding system. Original haematoxylin and eosin stained sections were reviewed, using light microscopy, to confirm classification and tumour differentiation. A total of 27 adenocarcinoma resection specimens were then assessed using immunohistochemistry for NY-ESO-1 expression: 4 well differentiated, 14 moderately differentiated, 4 moderate-poorly differentiated, and 5 poorly differentiated. Four out of a total of 27 cases of esophageal adenocarcinoma examined (15%) displayed diffuse cytoplasmic and nuclear expression for NY-ESO-1. They displayed a heterogeneous and mosaic-type pattern of diffuse staining. Diffuse cytoplasmic staining was not identified in any of these structures: stroma, normal squamous epithelium, normal submucosal gland and duct, Barrett's esophagus (goblet cell), Barrett's esophagus (non-goblet cell) and high grade glandular dysplasia. All adenocarcinomas showed an unexpected dot-type pattern of staining at nuclear, paranuclear and cytoplasmic locations. Similar dot-type staining, with varying frequency and size of dots, was observed on examination of Barrett's metaplasia, esophageal submucosal gland acini and the large bowel negative control, predominantly at the crypt base. Furthermore, a prominent pattern of apical (luminal) cytoplasmic dot-type staining was observed in some cases of Barrett's metaplasia and also adenocarcinoma. A further morphological finding of interest was noted on examination of haematoxylin and eosin stained sections, as aggregates of lymphocytes were consistently noted to surround submucosal glands. We have demonstrated for the first time NY-ESO-1 expression by esophageal adenocarcinomas, Barrett's metaplasia and normal tissues other than germ cells.

When is pre-emptive treatment necessary after endoscopic mucosal resection of early esophageal neoplasm?

When is pre-emptive treatment necessary after endoscopic mucosal resection of early esophageal neoplasm?

Risk factors associated with Barrett's epithelial dysplasia.

To elucidate risk factors associated with dysplasia of short-segment Barrett's esophagus (BE). A total of 151 BE patients who underwent endoscopic examination from 2004 to 2008 in Aoyama Hospital, Tokyo Women's Medical University, Japan and whose diagnosis was confirmed from biopsy specimens were enrolled in the study. BE was diagnosed based on endoscopic findings of gastric-appearing mucosa or apparent columnar-lined esophagus proximal to the esophagogastric junction. Dysplasia was classified into three grades - mild, moderate and severe - according to the guidelines of the Vienna Classification System for gastrointestinal epithelial neoplasia. Anthropometric and biochemical data were analyzed to identify risk factors for BE dysplasia. The prevalence of Helicobacter pylori (H. pylori) infection and the expression of p53 by immunohistological staining were also investigated. Histological examination classified patients into three types: specialized columnar epithelium (SCE) (n = 65); junctional (n = 38); and gastric fundic (n = 48). The incidence of dysplasia or adenocarcinoma from BE of the SCE type was significantly higher than that of the other two types (P < 0.01). The univariate analysis revealed that sex, H. pylori infection, body weight, p53 overexpression, and low diastolic blood pressure (BP) were associated with BE dysplasia. In contrast, body mass index, waist circumference, metabolic syndrome complications, and variables related to glucose or lipid metabolism were not associated with dysplasia. Multivariate logistic analysis showed that overexpression of p53 [odds ratio (OR) = 13.1, P = 0.004], H. pylori infection (OR = 0.19, P = 0.066), and diastolic BP (OR = 0.87, P = 0.021) were independent risk factors for epithelial dysplasia in BE patients with the SCE type. Overexpression of p53 is a risk factor for dysplasia of BE, however, H. pylori infection and diastolic BP inversely associated with BE dysplasia might be protective.

Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures

Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C(MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n=6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5mg (n=2), 0.5mg (n=2); Hal 5mg (n=2), 1.5mg (n=2), 0.5mg (n=2); TGF-β3 2μg (n=2), 0.5μg (n=2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80% or the animals were unable to maintain weight. The control group had a luminal diameter reduction of 78.2±10.9% by 2weeks and were euthanized by week 3. Compared at 2weeks, the Hal group showed a decrease in mean stricture formation (68.4% low dose, 57.7% high dose), while both TGF-β3 dosage groups showed no significant change (65.3% low dose, 76.2% high dose). MMC was most effective in stricture prevention (53.6% low dose, 35% high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formationafter EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.

Predictors of Response to Endoscopic Therapy of Barrettʼs High-Grade Dysplasia (HGD) and Intramucosal Cancer (IMC)

Purpose: Modalities of endoscopic therapy of Barrett's HGD and IMC include endoscopic mucosal resection (EMR), radiofrequency ablation (RFA), cryotherapy and argon plasma coagulation (APC). Although these are highly effective in most patients for eradication of dysplasia, some patients continue to have small areas of residual Barrett's or continue to progress to HGD or cancer. Our aims were to assess eradication rates of Barrett's metaplasia and dysplasia as well as factors which predict complete eradication. Methods: Review of prospectively collected database of patients who underwent endoscopic therapy for Barrett's dysplasia or IMC from 2006 to 2011. Patients who underwent EMR only excluded. Variables such as age, race, sex, BMI, alcohol use, smoking, diabetes, hypertension, hyperlipidemia, medication use were analyzed. Endoscopic data included length of Barrett's segment, hiatal hernia size, number of endoscopies and biopsy results. Results: Among 118 patients included, there were 60 patients in RFA and 58 patients in cryotherapy group. Compared to RFA patients, cryotherapy patients were found to be older and were more likely to have never used alcohol. In addition, they had longer treatment period and higher number of treatment sessions (table 1). Patients with RFA were more likely to have complete eradication of dysplasia (100% vs. 90%; p=0.012). There were no other significant differences between two groups. PREDICTORS: There was complete eradication of Barrett's in 72 patients (61%). There was Barrett's without dysplasia in 40 patients (33.8 %). Six patients had persistent HGD or progression to cancer (5%). On univariable analysis, subjects who had eradication of metaplasia had a longer treatment period (months 32.8± 20 vs 23.3±18.8, p=0.011) and follow-up time (months 36.8±21.5 vs. 25.9±18.7; p=0.006). There were no other significant differences. After adjusting for all variables in the model, subjects who had RFA had 3-fold higher odds of having eradication of metaplasia than those who had cryotherapy (odds ratio [OR] 2.9; 95% confidence interval [CI] 1.1-7.7; p = 0.031). In addition, for every 1 month increase in the EGD followup time, the odds of having complete metaplasia eradication increased by 4% (OR 1.04; 95% CI 1.01-1.07; p= 0.002). Younger age was associated with eradication of metaplasia/dysplasia (66.7± 10.6 vs. 75.8±9.3 years p=0.042). In addition, EMR and RFA were associated with eradication of metaplasia/dysplasia while patients without eradication were more likely to have had cryotherapy or APC/band ligation.Table 1: Endoscopic therapyConclusion: Endoscopic therapy is highly effective in eradication of Barrett's HGD and IMC. RFA with or without EMR and younger age are predictors for complete eradication of BE.

The Outcomes of Porfimer Sodium Photodynamic Therapy in Barrettʼs Dysplasia and Neoplasia: A Tertiary Center Experience

Purpose: Porfimer sodium photodynamic therapy (Ps-PDT) has been used to eradicate Barrett's dysplasia and neoplasia as an alternative to esophagectomy. The aim of this study was to assess the outcomes after Ps-PDT in patients with Barrett's esophagus with high grade dysplasia (HGD) or adenocarcinoma (ACA). Methods: This was a retrospective, observational study using large Ps-PDT database in a tertiary referral center. We reviewed the medical records of 136 patients (85 HGD; 51 ACA) with a median age of 73 (13% females). They were referred to our tertiary care center for PDT between 2001 and 2012. Initial evaluation included computed tomography and endosonography. Follow up endoscopy was performed 4-6 weeks after PDT with ablation of any residual Barrett's mucosa using argon plasma coagulation (APC). Patients were then followed thereafter every 3-6 months with computed tomography, endosonography and endoscopic surveillance with every 1-2 cm biopsies from the treated area. Results: The median follow up period was 15 months (range, 2-125 months). Eighteen of 136 patients underwent endoscopic mucosal resection (EMR) for nodular glandular mucosa prior to Ps-PDT. Ps-PDT was the only ablation treatment utilized in 28/136 patients. Of these patients, 12/28 (43%) achieved complete remission of intestinal metaplasia (CRIM). The other 7/28 patients had their histopathology downgraded after Ps-PDT. Nine other patients underwent Ps-PDT as palliative treatment for locally advanced neoplasia. One patient was lost for follow up immediately after PDT. Thirty out of 51 ACA patients (60%) achieved CRIM while 62/85 HGD patients (73%) achieved CRIM. The rate of recurrence of HGD was 10% (9/85) while that of ACA was 11% (6/50). Additional endoscopic therapy was required in a subset of patients including 14 patients who underwent EMR for persistent nodular disease after Ps-PDT and 41 patients treated with RFA for persisent or recurrent cases of BE. Complications after Ps-PDT included symptomatic strictures requiring endoscopic dilation in 43% (58 patients), while 7 patients had severe photosensitivity reactions. Conclusion: Overall, 83% of patients with esophageal HGD and ACA were successfully ablated or downgraded by Ps-PDT, either as a sole treatment or followed by focal ablation using argon plasma coagulation. These treatments were associated with a low rate of disease recurrence. Notable complications persist after PS-PDT, however, including strictures and cutaneous photosensitivity reactions. However, Ps-PDT remains an important endoscopic, minimally invasive treatment alternative to esophageal resection surgery for patients with Barrett's dysplasia and neoplasia. Disclosure - Dr. Waseem David - Research Fellow; Pinnacle Biologics, Grant/Research Support. This research was supported by an industry grant from Pinnacle Biologics.

Operatively induced chronic reflux in rats: A suitable model for studying esophageal carcinogenesis?

The mechanisms of esophageal reflux leading to esophageal adenocarcinoma (EA) remain poorly understood. This study appraises critically an operatively induced chronic reflux rat model. We randomized 108 Sprague-Dawley rats into 2 experimental groups; one was performing esophagoduodenal (ED) anastomosis with or without gastrectomy to induce duodeno-esophageal reflux (DER group; n = 63), and the other involved duodeno-gastro-esophageal reflux (DGER group; n = 45). Control groups included (i) Roux-en-Y esophagojejunal anastomosis, (ii) laparotomy alone, (iii) subtotal gastrectomy to induce duodenogastric reflux (DGR group), and (iv) the same procedure as in the DGER group plus proton pump inhibition (PPI group). The esophagus underwent histologic and molecular analyses. The prevalence of Barrett's esophagus (BE), dysplasia, and EA in the experimental groups was 41%, 7%, and 11%, respectively. Histologic and molecular analyses in groups DER, DGER, and DGR suggested that BE occurred through de novo intestinal metaplasia and proximal migration of duodenal cells. No distant metastases were identified. The molecular characteristics of both BE and EA were similar to humans. BE was more common, and dysplasia and EA less frequent in the DER group when compared with the DGER group (44% vs 24% [P = .038] and 7% vs 25% [P = .012], respectively). Compared with the DGER group, carcinogenic sequence occurred less frequently in the PPI-treated group (P = .019). Despite pathophysiologic differences with humans, the rat model of esophagoduodenostomy reproduces accurately histologic and molecular lesions in the carcinogenetic sequence of BE and allowed us to identify novel, tumor-associated proteins that may be potential biomarkers and new therapeutic targets in EA.

Long term efficacy of Photodynamic Therapy (PDT) as an ablative therapy of high grade dysplasia in Barrett's oesophagus

Barrett's high grade dysplasia (HGD) is a pre-malignant condition which requires treatment with either oesophagectomy or ablative endoscopic therapy. Endoscopic ablative techniques have evolved through Photodynamic Therapy (PDT) to more recently radiofrequency ablation (RFA). Although RFA has superseded PDT due to improved efficacy and safety profile there remains a significant cohort of patients previously treated by PDT where the long term outcome is unclear. This study's aim was to assess the long term efficacy of PDT in patients with Barrett's HGD. Between June 2002 and 2007 21 patients (16 male, median age 70) underwent PDT for HGD in Barrett's oesophagus. Patients received intravenous photosensitiser Photofrin (Porfimer sodium) forty eight hours prior to endoscopic light activation by laser light at 630 nm. The patients returned at 6-12 weekly intervals for repeat endoscopy and biopsy. Sixteen patients remained free of HGD at median 62 (range 36-114) months. Three patients developed adenocarcinoma at 47, 48 and 54 months (15%). Two patients were treated endoscopically with RFA and YAG laser, while one patient had surgical resection. Four patients developed recurrent HGD treated with repeat PDT. There was a significant reduction in length of Barrett's segment (from 5 cm to 3 cm) post PDT. The stricture rate requiring endoscopic therapy was 37% and 10% of patients developed photosensitivity reactions. PDT successfully ablated HGD in 84% of patients and could therefore still be considered an effective salvage treatment for this condition in patients with co-morbidities precluding them for surgical resection.

Nanoscale markers of esophageal field carcinogenesis: potential implications for esophageal cancer screening

Esophageal adenocarcinoma (EAC) has a dismal prognosis unless treated early or prevented at the precursor stage of Barrett's esophagus-associated dysplasia. However, some patients with cancer or dysplastic Barrett's esophagus (DBE) may not be captured by current screening and surveillance programs. Additional screening techniques are needed to determine who would benefit from endoscopic screening or surveillance. Partial wave spectroscopy (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld ), a statistic that characterizes the spatial distribution of the intracellular mass at the nanoscale level and thus provides insights into the cell nanoscale architecture beyond that which is revealed by conventional microscopy. The aim of the present study was to compare the disorder strength measured by PWS in normal squamous epithelium in the proximal esophagus to determine whether nanoscale architectural differences are detectable in the field area of EAC and Barrett's esophagus. During endoscopy, proximal esophageal squamous cells were obtained by brushings and were fixed in alcohol and stained with standard hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells was determined by PWS. A total of 75 patient samples were analyzed, 15 of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non-dysplastic Barrett's esophagus; 32 of the patients, most of whom had reflux symptoms, acted as controls. The mean disorder strength per patient in cytologically normal squamous cells in the proximal esophagus of patients with EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also had a disorder strength 1.63-times higher than controls (P<0.01). Intracellular nanoarchitectural changes were found in the proximal squamous epithelium in patients harboring distal EAC and DBE using PWS. Advances in this technology and the biological phenomenon of the field effect of carcinogenesis revealed in this study may lead to a useful tool in non-invasive screening practices in DBE and EAC.

Imaging the Upper Gastrointestinal Tract in Unsedated Patients Using Tethered Capsule Endomicroscopy

Endoscopic examination of the upper gastrointestinal tract is costly, inconvenient, and typically requires that the patient be sedated.1 Standard video endoscopy only provides macroscopic information so small, focal biopsies are excised in order to obtain a microscopic tissue diagnosis. Because there are few reliable visible cues for Barrett’s esophagus and dysplasia, crucial diagnostic regions can be missed. In order to overcome these limitations of endoscopy, we have integrated a microscopic imaging technology into a tethered capsule that can be swallowed. This new method, which we term tethered capsule endomicroscopy, provides microscopic information from the entire esophagus as the pill passes through the GI tract.

Endoscopic Raman spectroscopy enables objective diagnosis of dysplasia in Barrett's esophagus

Early detection and targeted endoscopic resection of Barrett's esophagus-associated high-grade dysplasia (HGD) can prevent progression to invasive esophageal malignancy. Raman spectroscopy, a highly sophisticated analytical technique, has been translated into an endoscopic tool to facilitate rapid, objective diagnosis of dysplasia in the esophagus. To evaluate the ability of endoscopic Raman spectroscopy (ERS) to objectively detect esophageal HGD and adenocarcinoma. A total of 798 one-second spectra were measured from 673 ex vivo esophageal tissue samples, collected from patients with Barrett's esophagus by using a novel endoscopic Raman probe. Spectra were correlated with consensus histopathology. Multivariate analysis was used to evaluate the classification accuracy of ERS ex vivo. Probe measurements were conducted in the laboratory. Tissue specimens were collected from the operating theatre and endoscopy unit. Tissue from 62 patients was included in the study. Endoscopic biopsy/resection or esophagectomy was performed where indicated clinically. Diagnostic performance of ERS for detection of HGD and esophageal adenocarcinoma. ERS demonstrated a sensitivity of 86% and a specificity of 88% for detecting HGD and adenocarcinoma. The ability to grade dysplasia and differentiate intestinal metaplasia from nonintestinal metaplasia columnar-lined esophagus was also demonstrated. Diagnostic classification was based on objective measurement of the biochemical profile of different tissue types. The potential for combination ERS and narrow-band imaging was also demonstrated. Measurements were taken from ex vivo tissue. ERS enables rapid, accurate, objective diagnosis of superficial esophageal disease (metaplasia, dysplasia, intramucosal cancer) in clinically applicable time scales.

Deciphering the Unique MicroRNA Signature in Human Esophageal Adenocarcinoma

Background and MethodsEsophageal adenocarcinoma (EAC) is characterized by a steep rise in incidence rates in the Western population. The unique miRNA signature that distinguishes EAC from other upper gastrointestinal cancers remains unclear. Herein, we performed a comprehensive microarray profiling for the specific miRNA signature associated with EAC. We validated this signature by qRT-PCR.ResultsMicroarray analysis showed that 21 miRNAs were consistently deregulated in EAC. miR-194, miR-192, miR-200a, miR-21, miR-203, miR-205, miR-133b, and miR-31 were selected for validation using 46 normal squamous (NS), 23 Barrett’s esophagus (BE), 17 Barrett’s high grade dysplasia (HGD), 34 EAC, 33 gastric adenocarcinoma (GC), and 45 normal gastric (NG) tissues. The qRT-PCR analysis indicated that 2 miRNAs (miR-21 and miR-133b) were deregulated in both EAC and GC, and 6 miRNAs (up-regulated: miR-194, miR-31, miR-192, and miR-200a; down-regulated: miR-203 and miR-205) in EAC, as compared to BE but not in GC, indicating their potential unique role in EAC. Our data showed that miR-194, miR-192, miR-21, and miR-31 were up-regulated in BE adjacent to HGD lesions relative to isolated BE samples. Analysis of clinicopathological features indicated that down-regulation of miR-203 is significantly associated with progression and tumor stages in EAC. Interestingly, the overexpression levels of miR-194, miR-200a, and miR-192 were significantly higher in early EAC stages, suggesting that these miRNAs may be involved in EAC tumor development rather than progression.ConclusionOur findings demonstrate the presence of a unique miRNA signature for EAC. This may provide some clues for the distinct molecular features of EAC to be considered in future studies of the role of miRNAs in EAC and their utility as disease biomarkers.

Su1474 Safety and Efficacy of Endoscopic Spray Cryotherapy for Barrett's Dysplasia: Results of the National Cryospray Registry

Safety and Efficacy of Endoscopic Spray Cryotherapy for Barrett’s Dysplasia: Results of the National Cryospray Registry Shireen Ghorbani*, Franklin Tsai, Bruce D. Greenwald, Sunguk Jang, John A. Dumot, Matthew Mckinley, Nicholas J. Shaheen, Fadlallah Habr, Walter Coyle Division of Gastroenterology and Hepatology, Scripps Green Hospital, La Jolla, CA; Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD; Division of Gastroenterology, Cleveland Clinic, Cleveland, OH; Division of Gastroenterology, University Hospitals Case Medical Center, Cleveland, OH; Division of Gastroenterology, Prohealth Syosset Hospital, Lake Success, NY; Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC; Division of Gastroenterology, University Medicine Foundation, Providence, RI Background: Endoscopic spray cryotherapy has been shown to be efficacious in eradicating high-grade dysplasia (HGD) in Barrett esophagus (BE) in multiple retrospective series. However, large prospective series evaluating the safety and efficacy of cryotherapy for Barrett’s dysplasia, particularly low grade dysplasia (LGD), have been lacking. Methods: A multicenter, prospective open-label registry study including subjects with BE and HGD or LGD. Primary outcomes were complete eradication of dysplasia and complete eradication of all intestinal metaplasia. Results: One hundred thirty-four subjects (mean age 67 years, 86% male) with Barrett’s dysplasia (29% LGD, 71% HGD; 37% SSBE, 63% LSBE; mean length 4.2 cm) underwent 464 treatments (mean 3.5 sessions per subject). There were no esophageal perforations, reports of severe pain, or related deaths. Strictures developed in 3 subjects, 2 of which required dilation. One subject was hospitalized for post cryotherapy bleeding in the setting of NSAID use requiring endoscopic hemostasis clip placement. Thirty-four percent of subjects reported mild to moderate post procedure symptoms. For subjects with LGD (mean length 5 cm), 26 (67%) had completed all planned cryotherapy treatments (mean 2.6 sessions) and were included in the efficacy analysis. Twenty-three subjects (88%) had complete eradication of all dysplasia and 16 (62%) had complete eradication of all intestinal metaplasia. For subjects with HGD (mean length 3.9 cm), 82 (86%) had completed all planned cryotherapy treatments (mean 3.5 sessions) and were included in the efficacy analysis. Seventy-five subjects (91%) had complete eradication of HGD, 69 (84%) had complete eradication of all dysplasia and 56 (68%) had complete eradication of all intestinal metaplasia. Conclusions: In the largest prospective cohort to date, short-term data suggest that endoscopic spray cryotherapy is a safe and highly effective modality for eradication of Barrett’s with LGD or HGD.

Su1461 The Impact of Wide-Area Endoluminal Resection on Endoscopic Therapy for Barrett's Dysplasia and Early Carcinoma

Su1461 The Impact of Wide-Area Endoluminal Resection on Endoscopic Therapy for Barrett's Dysplasia and Early Carcinoma

Mo1917 The Prague Classification Underestimates the True Maximal Extent and Dysplasia Grade of Barrett's Esophagus

Background: Endoscopic treatment by either radiofrequency (RFA) ablation or endoscopic mucosal resection (EMR) has become first line treatment for Barrett's esophagus (BE) with high grade dysplasia, while focal EMR and subsequent elimination of the residual segment by RFA or EMR is accepted therapy for intramucosal cancer (IMC). RFA and EMR are known to be clinically effective but the effect on the mRNA expression of molecular markers of disease stage, which may inform the long term risk of progression to adenocarcinoma, is unknown. We compared the mRNA expression profile in pre-treatment BE tissues biopsies and post-treatment neo-squamous tissues from the same level to provide a surrogatemolecular estimate of treatment effect. Methods: Paired pre-treatment BE tissues and post-treatment neosquamous biopsies were obtained from 38 patients treated by RFA (20 patients (3 IMC (prior EMR), 5 HGD, 12 LGD) or EMR (18 patients, 6 IMC, 12 HGD). mRNA expression of 16 genes significantly associated with different BE stages was measured using a multiplex tandem RT-PCR method with preand post-treatment tissues assessed simultaneously. Distal esophageal tissues from 12 patients with no history of GERD or BE were used as controls. Results: Endoscopic therapy resulted in a highly significant change in median values towards the squamous mucosa expression profile for all 16 genes on unpaired analysis. This change remained significant for 12 genes by paired analysis (t test). The only significant treatment differences in pre-post mean difference in gene expression were greater changes for RFA compared to EMR for 5 genes. The neosquamous expression profile was significantly different to the control profile for 9 of 16 genes. Conclusions: Both RFA and EMR result in marked changes in mRNA expression, with replacement of the highly disordered Barrett's dysplasia or IMC expression profile with a more normal expression profile. The neosquamous mucosa was significantly different to the control squamous mucosa for most genes but the significance of this finding is uncertain and may reflect confounding factors.

Mo1916 Gene Expression Pre- and Post-Endoscopic RFA or EMR Treatment for Dysplastic Barrett's Esophagus or Intramucosal Adenocarcinoma

Background: Endoscopic treatment by either radiofrequency (RFA) ablation or endoscopic mucosal resection (EMR) has become first line treatment for Barrett's esophagus (BE) with high grade dysplasia, while focal EMR and subsequent elimination of the residual segment by RFA or EMR is accepted therapy for intramucosal cancer (IMC). RFA and EMR are known to be clinically effective but the effect on the mRNA expression of molecular markers of disease stage, which may inform the long term risk of progression to adenocarcinoma, is unknown. We compared the mRNA expression profile in pre-treatment BE tissues biopsies and post-treatment neo-squamous tissues from the same level to provide a surrogatemolecular estimate of treatment effect. Methods: Paired pre-treatment BE tissues and post-treatment neosquamous biopsies were obtained from 38 patients treated by RFA (20 patients (3 IMC (prior EMR), 5 HGD, 12 LGD) or EMR (18 patients, 6 IMC, 12 HGD). mRNA expression of 16 genes significantly associated with different BE stages was measured using a multiplex tandem RT-PCR method with preand post-treatment tissues assessed simultaneously. Distal esophageal tissues from 12 patients with no history of GERD or BE were used as controls. Results: Endoscopic therapy resulted in a highly significant change in median values towards the squamous mucosa expression profile for all 16 genes on unpaired analysis. This change remained significant for 12 genes by paired analysis (t test). The only significant treatment differences in pre-post mean difference in gene expression were greater changes for RFA compared to EMR for 5 genes. The neosquamous expression profile was significantly different to the control profile for 9 of 16 genes. Conclusions: Both RFA and EMR result in marked changes in mRNA expression, with replacement of the highly disordered Barrett's dysplasia or IMC expression profile with a more normal expression profile. The neosquamous mucosa was significantly different to the control squamous mucosa for most genes but the significance of this finding is uncertain and may reflect confounding factors.

Mo1918 Adherence to the 2011 AGA Medical Position Statement for the Treatment of Barrett's Esophagus

Background: Endoscopic treatment by either radiofrequency (RFA) ablation or endoscopic mucosal resection (EMR) has become first line treatment for Barrett's esophagus (BE) with high grade dysplasia, while focal EMR and subsequent elimination of the residual segment by RFA or EMR is accepted therapy for intramucosal cancer (IMC). RFA and EMR are known to be clinically effective but the effect on the mRNA expression of molecular markers of disease stage, which may inform the long term risk of progression to adenocarcinoma, is unknown. We compared the mRNA expression profile in pre-treatment BE tissues biopsies and post-treatment neo-squamous tissues from the same level to provide a surrogatemolecular estimate of treatment effect. Methods: Paired pre-treatment BE tissues and post-treatment neosquamous biopsies were obtained from 38 patients treated by RFA (20 patients (3 IMC (prior EMR), 5 HGD, 12 LGD) or EMR (18 patients, 6 IMC, 12 HGD). mRNA expression of 16 genes significantly associated with different BE stages was measured using a multiplex tandem RT-PCR method with preand post-treatment tissues assessed simultaneously. Distal esophageal tissues from 12 patients with no history of GERD or BE were used as controls. Results: Endoscopic therapy resulted in a highly significant change in median values towards the squamous mucosa expression profile for all 16 genes on unpaired analysis. This change remained significant for 12 genes by paired analysis (t test). The only significant treatment differences in pre-post mean difference in gene expression were greater changes for RFA compared to EMR for 5 genes. The neosquamous expression profile was significantly different to the control profile for 9 of 16 genes. Conclusions: Both RFA and EMR result in marked changes in mRNA expression, with replacement of the highly disordered Barrett's dysplasia or IMC expression profile with a more normal expression profile. The neosquamous mucosa was significantly different to the control squamous mucosa for most genes but the significance of this finding is uncertain and may reflect confounding factors.

Mo1915 Durability of Photodynamic Therapy for Barrett's Dysplasia: A Single Center 20-Year Experience

Mo1915 Durability of Photodynamic Therapy for Barrett's Dysplasia: A Single Center 20-Year Experience

346 Prediction of Response to Endoscopic Therapy of Barrett's Dysplasia using FISH Biomarkers

346 Prediction of Response to Endoscopic Therapy of Barrett's Dysplasia using FISH Biomarkers