Search

Background & Aims Increased waist circumference and visceral fat are associated with increased risk of Barrett's esophagus (BE) and esophageal adenocarcinoma. This association might be mediated by mechanical and endocrine mechanisms. We investigated the distribution of fat in subjects with BE and its association with esophageal inflammation and dysplasia. Methods We collected data from 50 BE cases and 50 controls (matched for age and sex, identified from a radiology trauma database) seen at the Mayo Clinic in 2009. Abdominal (subcutaneous and visceral) and gastroesophageal junction (GEJ) fat area was measured using computed tomography with standard techniques. Esophageal inflammation (based on a histologic score) and dysplasia grade were assessed from esophageal biopsies of BE cases by a gastrointestinal pathologist. Conditional logistic regression was used to assess the association of body fat depot area with BE status, esophageal inflammation, and dysplasia. Results All BE subjects had controlled reflux symptoms without esophagitis, based on endoscopy. The GEJ fat area (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.3–27.7; P = .02), visceral fat area (OR, 4.9; 95% CI, 1.0–22.8; P = .04), and abdominal circumference (OR, 9.1; 95% CI, 1.4–57.2; P = 0.02) were associated with BE, independent of body mass index (BMI). The subcutaneous fat area was not associated with BE. Visceral and GEJ fat were significantly greater in BE subjects with esophageal inflammation (compared with those without, P = .02) and high-grade dysplasia (compared with those without, P = .01), independent of BMI. Conclusions GEJ and visceral fat are associated with BE, and with increased esophageal inflammation and high-grade dysplasia in BE subjects, independent of BMI. Visceral fat therefore might promote esophageal metaplasia and dysplasia.

SUMMARY The management of high-grade dysplasia in Barrett's esophagus has clearly changed over recent years. The risk of cancer development is still substantial, with about one in three patients developing cancer, but a number of patients do not develop cancer. The nature of high-grade dysplasia has also been genetically elucidated with more evidence of chromosomal instability being present at this stage than previously thought. Therapy of the condition has evolved more toward endoscopic therapy, given the good results of radio-frequency ablation and photodynamic therapy in eliminating dysplasia and decreasing cancer development in randomized controlled trial. The best candidates for treatment include compliant patients that have relatively short segments of Barrett's esophagus, an anatomically straight segment, lack of nodularity, and an intact p16. However, even with excellent long-term results similar to surgical resection, the risk of recurrence is present in over 14% of patients, which indicates that there will be a need to continue surveillance endoscopy in these patients.

Background & Aims Radiofrequency ablation (RFA) is safe and effective treatment for flat dysplasia associated with Barrett's esophagus (BE). However, there are limited data on the safety of RFA in patients who had prior endoscopic mucosal resection (EMR), which might increase the risk of complications. We compared complications and histologic outcomes between patients who had EMR before RFA and those who received only RFA. Methods We performed a retrospective analysis of data collected from patients treated for BE, associated with dysplasia or intramucosal cancer, at the Mayo Clinic in Rochester, Minnesota, from 1998–2009. Patients were divided into groups that had RFA after EMR (group 1, n=44) or only RFA (group 2, n=46). We compared the incidence of complications (strictures, bleeding, and esophageal perforation) and histologic features (complete resolution of dysplasia and complete resolution of intestinal metaplasia [CR-IM]) between groups. Logistic regression analysis was performed to assess predictors of stricture formation. Results Stricture rates were 14% in group 1 and 9% in group 2 (odds ratio, 1.53; 95% confidence interval [CI], 0.26–9.74). The rates of CR-IM were 43% in group 1 and 74% in group 2 (odds ratio, 0.33; 95% CI, 0.14–0.78). The rates of complete resolution of dysplasia were 76% in group 1 and 71% in group 2 (odds ratio, 1.28; 95% CI, 0.39–4.17). The adjusted odds ratio for CR-IM in group 1 (adjusting for age, segment length, and grade of dysplasia) was 0.50 (95% CI, 0.15–1.66). Conclusions Stricture rates among patients who receive only RFA are comparable to those of patients who had prior EMR. EMR appears safe to perform prior to RFA.

Background: Genetic influences may be discerned in families that have multiple affected members and may manifest as an earlier age of cancer diagnosis. In this study, we determine whether cancers develop at an earlier age in multiplex Familial Barrett's Esophagus (FBE) kindreds, defined by 3 or more members affected by Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC). Methods: Information on BE/EAC risk factors and family history was collected from probands at eight tertiary care academic hospitals. Age of cancer diagnosis and other risk factors were compared between nonfamilial (no affected relatives), duplex (two affected relatives), and multiplex (three or more affected relatives) FBE kindreds. Results: The study included 830 nonfamilial, 274 duplex, and 41 multiplex FBE kindreds with 274, 133, and 43 EAC and 566, 288, and 103 BE cases, respectively. Multivariable mixed models adjusting for familial correlations showed that multiplex kindreds were associated with a younger age of cancer diagnosis (P = 0.0186). Median age of cancer diagnosis was significantly younger in multiplex compared with duplex and nonfamilial kindreds (57 vs. 62 vs. 63 years, respectively, P = 0.0448). Mean body mass index was significantly lower in multiplex kindreds (P = 0.0033), as was smoking (P < 0.0001), and reported regurgitation (P = 0.0014). Conclusions: Members of multiplex FBE kindreds develop EAC at an earlier age compared with nonfamilial EAC cases. Multiplex kindreds do not have a higher proportion of common risk factors for EAC, suggesting that this aggregation might be related to a genetic factor. Impact: These findings indicate that efforts to identify susceptibility genes for BE and EAC will need to focus on multiplex kindreds. Cancer Epidemiol Biomarkers Prev; 21(2); 376–83. ©2011 AACR.

OBJECTIVE To assess the feasibility of unsedated transnasal endoscopy (uTNE) and video capsule endoscopy (VCE) as alternatives to sedated endoscopy (sEGD) as screening tools for Barrett esophagus (BE) and to obtain preliminary estimates of participation rates for sEGD, uTNE, and VCE when used for community BE screening in a population cohort. PATIENTS AND METHODS From February 1, 2009, to May 31, 2010, patients from Olmsted County, Minnesota, who were older than 50 years and had no history of known BE were randomized (stratified by age, sex, reflux symptoms noted in a validated questionnaire) into 3 groups for esophageal evaluation with sEGD, uTNE, or VCE. Participation rates and safety profiles were estimated. RESULTS We contacted 127 patients to recruit 20 for each procedure arm (60 total). The probability of participation was 38% (95% confidence interval [CI], 26%-51%) for sEGD, 50% (95% CI, 35%-65%) for uTNE, and 59% (95% CI, 42%-74%) for VCE. Both uTNE and VCE were well tolerated without adverse effects. BE was identified in 3 patients and esophagitis in 8. CONCLUSION Unsedated techniques may be acceptable, feasible, and safe alternatives to sEGD to screen for BE in the community. Trial Registration: clinicaltrials.gov Identifier: NCT00943280

Population-based data on the epidemiology and outcomes of subjects with intestinal metaplasia of the gastroesophageal junction (IMGEJ) and Barrett's esophagus (BE) are limited. The objectives of this study were to (i) estimate the incidence of IMGEJ and BE diagnosed from clinically indicated endoscopy in Olmsted County, MN, over three decades (1976-2006) and prevalence as of 1 January 2007, (ii) compare baseline characteristics of subjects with IMGEJ and BE, and (iii) study the natural history and survival of both cohorts.This was a population-based cohort study. The study setting was Olmsted County, MN. Patients with BE (columnar segment1 cm with intestinal metaplasia) and IMGEJ (intestinal metaplasia in biopsies from the gastroesophageal junction) from 1976 to 2006 in Olmsted County, MN, were identified using Rochester Epidemiology Project resources. Demographic and clinical data were abstracted from medical records and pathology confirmed by gastrointestinal pathologists. The association of baseline characteristics with overall and progression-free survival was assessed using proportional hazards regression models. Outcome measures were baseline characteristics and overall survival of subjects with IMGEJ compared to those with BE.In all, 487 patients (401 with BE and 86 with IMGEJ) were identified and followed for a median interval of 7 (BE subjects) to 8 (IMGEJ subjects) years. Subjects with BE were older, heavier, reported reflux symptoms more often, and had higher prevalence of advanced neoplasia than those with IMGEJ. No patient with IMGEJ progressed to esophageal adenocarcinoma (EAC) in contrast to BE subjects who had a cumulative risk of progression of 7% at 10 years and increased risk of death from EAC (standardized mortality ratio 9.62). The overall survival of subjects with BE and IMGEJ did not differ from that expected in similar age- and sex-distributed white Minnesota populations.Subjects with IMGEJ appear to have distinct clinical characteristics and substantially lower cancer progression risk compared to those with BE.

Background & Aims There is controversy over the outcomes of esophageal adenocarcinoma with superficial submucosal invasion. We evaluated the impact of depth of submucosal invasion on the presence of metastatic lymphadenopathy and survival in patients with esophageal adenocarcinoma. Methods Pathology reports of esophagectomy samples collected from 1997 to 2007 were reviewed. Specimens from patients with esophageal adenocarcinoma and submucosal invasion were reviewed and classified as superficial (upper 1 third, sm1) or deep (middle third, sm2 or deepest third, sm3) invasion. Outcomes studied were presence of metastatic lymphadenopathy and overall survival. Variables of interest were analyzed as factors that affect overall and cancer-free survival using Cox proportional hazards modeling. A multivariate model was constructed to establish independent associations with survival. Results The study included 80 patients; 31 (39%) had sm1 carcinoma, 23 (29%) had sm2 carcinoma, and 26 (33%) had sm3 carcinoma. Superficial and deep submucosal invasion were associated with substantial rates of metastatic lymphadenopathy (12.9% and 20.4%, respectively). The mean follow-up time was 40.5 ± 4 months and the mean overall unadjusted survival time was 53.8 ± 4.1 months. Factors significantly associated with reduced survival time included the presence of metastatic lymph nodes (hazard ratio [HR], 2.89; confidence interval [CI], 1.13–6.88) and esophageal cancer recurrence (HR 6.39, CI 2.40–16.14), but not depth of submucosal invasion. Conclusions Patients with sm1 esophageal carcinoma have substantial rates of metastatic lymphadenopathy. Endoscopic treatment of superficial submucosal adenocarcinoma is not advised for patients that are candidates for surgery.

The ability to visualize in vivo microscopic areas of neoplasia within gastrointestinal mucosa has been a major quest of modern gastroenterology. The attainment of this goal could revolutionize the diagnosis and treatment of neoplastic disease. Potential benefits could include the elimination of random biopsies for surveillance of mucosal disease and increasing time intervals between surveillance endoscopy, elimination of sampling error issues, decrease inter-procedural discrepancies regarding the presence and magnitude of dysplasia present and ultimately to improve patient outcomes with at risk neoplasia. Recent advances in endocytoscopy can help guide the early detection of malignancy and lead to earlier treatment. Endocytoscopy is a new imaging and magnification technology classified as one of the “contact devices”, has been developed for observation of cellular structure in vivo with particular application in the esophagus. The technology can provide accurate targeting of lesions with an in vivo “virtual histological diagnosis” and could enhance endoscopic surveillance by decreasing biopsies of normal appearing mucosa. The purpose of this review is to survey the technology available and examine the literature to date regarding its clinical usage. We will also conclude this review with potential future directions.

Photodynamic therapy was the first treatment to have been shown to significantly decrease high-grade dysplasia and cancer in patients with Barrett’s esophagus. However, its use has been limited, primarily because of the side effects, which include esophageal strictures, cutaneous photosensitivity, chest pain, and nausea and vomiting [1]. The tolerability aspects of photodynamic therapy, as well as the dosimetry, though, can be improved with existing technologies to further develop this therapy into truly a widely applicable therapy. Studies have recently been done to help identify patients more likely to suffer stricture after photodynamic therapy. In addition, there has been evidence to suggest that the efficacy of photodynamic therapy also can be limited by genetic abnormalities in the mucosa. By combining knowledge of tissue biology, optical properties of the tissue, and dosimetry issues with ablation, photodynamic therapy can still have a potentially bright future.

Barrett esophagus (BE) predisposes patients to esophageal adenocarcinoma, a cancer with one of the fastest rising incidence rates over the past decade and a highly lethal malignancy once it is symptomatic.1,2 It is believed that esophageal adenocarcinoma arises as the final step of a postulated sequential change in the metaplastic epithelium, progressing from low-grade dysplasia (LGD), to high-grade dysplasia (HGD), and finally carcinoma. HGD on histologic samples has been used as the most reliable clinical biomarker of potential carcinogenesis, with studies reporting variable rates of progression to esophageal carcinoma (range, 16%–59%).3–5 Interruption of the metaplasia-dysplasia-carcinoma sequence by ablating or resecting this at-risk mucosa has been proposed as a strategy to reduce the incidence of esophageal adenocarcinoma and has served as the rationale for the recommendation of esophagectomy for patients with HGD. Over the past few years, endoscopic therapy has emerged as an alternative to esophagectomy because of the significant mortality and morbidity associated with esophagectomy.6,7 Multiple modalities, including photodynamic therapy (PDT),8 argon plasma coagulation,9 and multipolar electrocoagulation10 in isolation and in combination with endoscopic mucosal resection (EMR),11,12 have been reported in the treatment of HGD. Variable success rates have been reported (range, 75%–90%). A randomized multicenter trial compared PDT with surveillance and treatment with omeprazole in patients with HGD. After a 24-month follow-up, complete ablation of HGD was noted in 77% of patients versus 39% in the omeprazole group. Thirteen percent of patients who received PDT plus omeprazole progressed to cancer compared with 28% of patients in the omeprazole group.13 This led to U.S. Food and Drug Administration approval for the use of PDT for the treatment of HGD in BE. We recently reported that long-term outcomes (overall mortality and cancer-free survival) were comparable between patients who underwent esophagectomy and patients who received PDT.14 Several genetic alterations have been described in BE. These include loss of cell cycle checkpoint genes, such as p16 and p53. Loss of these genes by allelic loss (deletions or loss of heterozygosity [LOH]), point mutations, or promoter hypermethylation (for p16) have been observed in a substantial number of patients with BE.15,16 Several other genetic alterations that involve gains/amplifications of proto-oncogenes (and growth factors/growth factor receptors) as well as changes in DNA content (as assessed by flow cytometry and image cytometry) also have been described.17,18 Currently, histology is used as the endpoint to define success with ablative therapy in HGD. However, recurrences and/or progression to cancer despite ‘successful’ ablation/resection are common. To our knowledge, predictors of recurrent dysplasia have not been defined. Few studies have assessed genetic alterations after ablation of BE19–21: those studies primarily assessed patients with predominantly nondysplastic BE (a category for which ablation currently is not recommended) rather than HGD (in which endoscopic ablation is gaining acceptance as an alternative to esophagectomy) by using techniques that lack long-term data on successful ablation. Studies also have raised concern about the appearance of cancer-associated biomarkers after ablation (in patients with nondysplastic BE)20: however, data are lacking on the clinical implication of this phenomenon in terms of the recurrence or progression of dysplasia. The role of biomarkers in defining response to PDT remains unclear. The correlation between histologic response and ‘biomarker response’ also is unknown. We hypothesized that patients who remain positive for genetic alterations despite achieving a histologic response to PDT would be at risk for recurrence of dysplasia. In this study, we used fluorescence in situ hybridization (FISH) to characterize genetic alterations that were present in patients with HGD and mucosal cancer before treatment with PDT and compared them with the alterations observed after PDT. In addition, we assessed the recurrence of dysplasia after initial histologic response and correlated those findings with post-PDT genetic alterations assessed by FISH.

Background & Aims: Photodynamic therapy (PDT) for high-grade dysplasia (HGD) in Barrett's esophagus is a Food and Drug Administration–approved alternative to esophagectomy. Critical information regarding overall survival of patients followed up long-term after these therapies is lacking. Our aim was to compare the long-term survival of patients treated with PDT with patients treated with esophagectomy. Methods: We reviewed records of patients with HGD seen at our institution between 1994 and 2004. PDT was performed 48 hours following the intravenous administration of a photosensitizer using light at 630 nm. Esophagectomy was performed by either transhiatal or transthoracic approaches by experienced surgeons. We excluded all patients with evidence of cancer on biopsy specimens. Vital status and death date information was queried using an institutionally approved Internet research and location service. Statistical analysis was performed using Kaplan–Meier curves and Cox proportional hazards ratios. Results: A total of 199 patients were identified. A total of 129 patients (65%) were treated with PDT and 70 (35%) with esophagectomy. Overall mortality in the PDT group was 9% (11/129) and in the surgery group was 8.5% (6/70) over a median follow-up period of 59 ± 2.7 months for the PDT group and 61 ± 5.8 months for the surgery group. Overall survival was similar between the 2 groups (Wilcoxon test=0.0924; P = .76). Treatment modality was not a significant predictor of mortality on multivariate analysis. Conclusions: Overall mortality and long-term survival in patients with HGD treated with PDT appears to be comparable to that of patients treated with esophagectomy.

Objective. Guidelines on antiplatelet medication use during endoscopy are based on limited evidence. We investigate the risk of bleeding and ischemic events in patients undergoing endoscopic mucosal resection (EMR) of esophageal lesions in the setting of scheduled cessation and prompt resumption of clopidogrel. Design. Single centre retrospective review. Patients. Patients undergoing EMR of esophageal lesions. Interventions. Use of clopidogrel before EMR and resumption after EMR. Patients cease antiplatelets and anticoagulants 7 days before EMR and resume clopidogrel 2 days after EMR in average risk patients. Main Outcomes. Gastrointestinal bleeding (GIB) and ischemic events (IE) within 30 days of EMR. Results. 798 patients underwent 1716 EMR. 776 EMR were performed on patients on at least 1 antiplatelet/anticoagulant (APAC). 17 EMR were performed following clopidogrel cessation. There were 14 GIB and 2 IE. GIB risk in the setting of recent clopidogrel alone (0%) was comparable to those not on APAC (1.1%) (P=1.0). IE risk on clopidogrel (6.3%) was higher than those not on APAC (0.1%) (P=0.03). Limitations. Retrospective study. Conclusions. Temporary cessation of clopidogrel before EMR and prompt resumption is not associated with an increased risk of gastrointestinal bleeding but may be associated with increased ischemic events.

Purpose of review Endoscopic eradication therapy is considered a well tolerated and effective alternative to esophagectomy for a select patient population with high-grade Barrett's esophagus and intramucosal adenocarcinoma. This review highlights the available eradication techniques (resection and ablation) with emphasis on factors that influence the choice of therapy. Recent findings Long-term follow-up of patients treated with endoscopic eradication therapies demonstrates high rates of complete remission of dysplasia and intestinal metaplasia with overall survival comparable to patients treated surgically. Cohort studies also report that recurrence following successful ablation occurs in a significant proportion of patients, making careful surveillance an indispensable component following successful endoscopic therapy. Endoscopic eradication therapy is also effective for the treatment of recurrent dysplasia and intestinal metaplasia. Ablative therapies may lead to buried metaplasia in a small proportion of patients. The long-term clinical implications of buried metaplasia are unclear. Summary Patients undergoing endoscopic eradication therapy should be enrolled in a comprehensive surveillance and staging program that offers both resection and ablative techniques. Complete remission of dysplasia and intestinal metaplasia can be achieved in the vast majority of patients undergoing endoscopic therapy. Surveillance should continue after treatment with close monitoring for recurrent dysplasia.

Enhanced visualization techniques are available for Barrett's esophagus and have promise in the detection of dysplasia and cancer. Several of these techniques, such as narrow band imaging and chromoendoscopy, are being applied clinically. These techniques will allow the endoscopist to screen the surface of the Barrett's esophagus to detect areas of neoplasia. Once detected, it is hoped that either magnification techniques, such as confocal laser endomicroscopy, or spectroscopic techniques can be of value in allowing in vivo real-time diagnostic capabilities.

To summarize the literature to date on endoscopic mucosal removal techniques as applied to the upper gastrointestinal tract, predominantly the stomach and esophagus. This is an area that has rapidly advanced in terms of new procedures and techniques with a large body of outcomes that support their use.The resection techniques can be divided into two forms, mucosal resection and submucosal dissection. Mucosal resection is typically done with cap techniques and is more suitable for removable of neoplastic lesions that are less than 1.5 cm in size. Submucosal dissection techniques are more difficult, associated with increased complications, and typically reserved for lesions greater than 1.5 cm and less than 3 cm in size. Ideal lesions for mucosal resection are generally flat and are located in areas easily accessible by the endoscope.Endoscopic tissue removal methods are capable of removing neoplastic lesions en bloc in the upper gastrointestinal tract. These techniques fulfill cancer treatment guidelines by having histological confirmation of total removal of neoplastic lesions with assessment of the margins of resections. Long-term clinical outcomes of these techniques are emerging and seem promising in terms of disease-free and overall survival.

Background & Aims Endoscopic tri-modal imaging (ETMI) incorporates high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow band imaging (NBI). A recent uncontrolled study found that ETMI improved the detection of high-grade dysplasia (HGD) and early carcinoma (Ca) in Barrett's esophagus (BE). The aim was to compare ETMI with standard video endoscopy (SVE) for the detection of HGD/Ca with the use of a randomized cross-over design. Methods Patients referred for work-up of inconspicuous HGD/Ca were eligible and underwent both SVE and ETMI in randomized order within an interval of 6–12 weeks. During ETMI, inspection with HRE was followed by AFI. Detected lesions were inspected in detail with NBI and biopsied, followed by random biopsies. During SVE, any visible lesion was biopsied followed by random biopsies. Results Eighty-seven patients with BE underwent ETMI and SVE. No significant difference was observed in overall histologic yield between ETMI and SVE. ETMI had a significantly higher targeted yield compared with SVE because of AFI. However, the yield of targeted biopsies of ETMI was significantly inferior to the overall yield of SVE. Detailed inspection with NBI reduced the false-positive rate of HRE + AFI from 71% to 48% but misclassified 17% of HGD/Ca lesions as not suspicious. Conclusions ETMI statistically significant improves the targeted detection of HGD/Ca compared with SVE. Subsequent characterization of lesions with NBI appears to be of limited value. At this stage, ETMI cannot replace random biopsies for detection of lesions or targeted biopsies for characterization of lesions in a high-risk population.

Barrett's esophagus (BE) is the strongest risk factor for esophageal adenocarcinoma (EAC), a malignancy with persistently poor long-term outcomes. EAC is thought to develop through progression of metaplasia to dysplasia to invasive carcinoma. Identification of factors predicting progression to EAC would help in focusing surveillance, chemoprevention, or ablation for those deemed to be at highest risk of progression. We performed a comprehensive review of the literature and summarized current evidence on risk factors for progression in subjects with known BE. Clinical and demographic factors (age, male gender, length of BE segment) are associated with modestly increased odds of progression to EAC in some studies. Biomarkers such as aneuploidy and p53 loss of heterozygosity have been associated with increased risk of progression to high-grade dysplasia and/or EAC in single-center prospective cohort studies. Promising newer techniques and markers have been recently reported with the potential to help risk stratify BE subjects. Development of a comprehensive BE risk progression score comprised of both clinical and biomarker variables should be the ultimate goal and can be achieved by multicenter prospective collaborative efforts. Although it would be challenging, creation of such a score has the potential to improve outcomes and make the management of patients with BE more cost-effective.

This report is written as an adjunct to the American Gastroenterological Association Institute’s medical position statement and technical review on the management of Barrett’s esophagus, which will be published in the near future. Those documents will consider a number of broad questions on the diagnosis, clinical features, and management of patients with Barrett’s esophagus, and the reader is referred to the technical review for an in-depth discussion of those topics. In this report, we review historical, molecular, and endoscopic therapeutic aspects of Barrett’s esophagus that are of interest to clinicians and researchers.

Endoscopic mucosal resection has expanded the role of the gastroenterologist in the management of esophageal neoplasia from screening and diagnosis to staging and endoscopic treatment. Its rise to prominence is a reflection of the long-identified need to obtain histologic information regarding depth of invasion and neoplastic margins during therapy that previously could not be achieved with ablative techniques. The resultant improvement in diagnosis and staging has allowed for better selection of patients for endoscopic therapy who may be spared invasive surgery. The clinical indications, endoscopic techniques, outcomes, and complications in the management of esophageal neoplasia are reviewed. Training requirements to achieve proficiency in endoscopic mucosal resection as well as potential quality measures to assess competence also are proposed in this review.

Background & Aims Endoscopic therapy is emerging as an alternative to surgical therapy in patients with mucosal (T1a) esophageal adenocarcinoma (EAC) given the low likelihood of lymph node metastases. Long-term outcomes of patients treated endoscopically and surgically for mucosal EAC are unknown. We compared long-term outcomes of patients with mucosal EAC treated endoscopically and surgically. Methods Patients treated for mucosal EAC between 1998 and 2007 were included. Patients were divided into an endoscopically treated group (ENDO group) and a surgically treated group (SURG group). Vital status information was queried using an institutionally approved internet research and location service. Statistical analysis was performed using Kaplan–Meier curves and Cox proportional hazard ratios. Results A total of 178 patients were included, of whom 132 (74%) were in the ENDO group and 46 (26%) were in the SURG group. The mean follow-up period was 64 months (standard error of the mean, 4.8 mo) in the SURG group and 43 months (standard error of the mean, 2.8 mo) in the ENDO group. Cumulative mortality in the ENDO group (17%) was comparable with the SURG group (20%) ( P = .75). Overall survival also was comparable using the Kaplan–Meier method. Treatment modality was not a significant predictor of survival on multivariable analysis. Recurrent carcinoma was detected in 12% of patients in the ENDO group, all successfully re-treated without impact on overall survival. Conclusions Overall survival in patients with mucosal EAC when treated endoscopically appears to be comparable with that of patients treated surgically. Recurrent carcinoma occurs in a limited proportion of patients, but can be managed endoscopically.

Background The incidence and risk factors for recurrence of dysplasia after ablation of Barrett's esophagus (BE) have not been well defined. Objective To determine the rate and predictors of dysplasia/neoplasia recurrence after photodynamic therapy (PDT) in BE. Setting Retrospective analysis of a prospective cohort of BE patients seen at a specialized BE unit. Methods Patients underwent a standard protocol assessment with esophagogastroduodenoscopy and 4-quadrant biopsies every centimeter at 3-month intervals after ablation. Recurrence was defined as the appearance of any grade of dysplasia or neoplasia after 2 consecutive endoscopies without dysplasia. Entry histology, demographics, length of BE, presence and length of diaphragmatic hernia, EMR, stricture formation, nonsteroidal anti-inflammatory drug use, smoking, and the presence of nondysplastic BE or squamous epithelium were assessed for univariate associations. Time-to-recurrence analysis was done by using Cox proportional hazards regression. A multivariate model was constructed to establish independent associations with recurrence. Results A total of 363 patients underwent PDT with or without EMR. Of these, 261 patients were included in the final analysis (44 lost to follow-up, 46 had residual dysplasia, and 12 had no dysplasia at baseline). Indication for ablation was low-grade dysplasia (53 patients, 20%), high-grade dysplasia (152 patients, 58%), and intramucosal cancer (56 patients, 21%). Median follow-up was 36 months (interquartile range 18-79 months). Recurrence occurred in 45 patients. Median time to recurrence was 17 months (interquartile range 8-45 months). Significant predictors of recurrence on the multivariate model were older age (hazard ratio [HR] 1.04, P=.029), presence of residual nondysplastic BE (HR 2.88, P=.012), and a history of smoking (HR 2.68, P=.048). Limitations Possibility of missing prevalent dysplasia despite aggressive surveillance. Conclusion Recurrence of dysplasia/neoplasia after PDT ablation is associated with advanced age, smoking, and residual BE.

Background & Aims Data on secular trends and outcomes of eosinophilic esophagitis (EE) are scarce. We performed a population-based study to assess the epidemiology and outcomes of EE in Olmsted County, Minnesota, over the last 3 decades. Methods All cases of EE diagnosed between 1976 and 2005 were identified using the Rochester Epidemiology Project resources. Esophageal biopsies with any evidence of esophagitis and/or eosinophilic infiltration were reviewed by a single pathologist. Clinical course (treatment, response, and recurrence) was defined using information collected from medical records and prospectively via a telephone questionnaire. Incidence rates per 100,000 person years were directly adjusted for age and sex to the US 2000 population structure. Results A total of 78 patients with EE were identified. The incidence of EE increased significantly over the last 3 of the 5-year intervals (from 0.35 [95% confidence interval (CI)], 0–0.87] per 100,000 person-years during 1991–1995 to 9.45 [95% CI, 7.13–11.77] per 100,000 person-years during 2001–2005). The prevalence of EE was 55.0 (95% CI, 42.7–67.2) per 100,000 persons as of January 1, 2006, in Olmsted County, Minnesota. EE was diagnosed more frequently in late summer/fall. The clinical course of patients with EE was characterized by recurrent symptoms (observed in 41% of patients). Conclusions The prevalence and incidence of EE is higher than previously reported. The incidence of clinically diagnosed EE increased significantly over the last 3 decades, in parallel with endoscopy volume. Seasonal incidence was greatest in late summer and fall. EE also appears to be a recurrent relapsing disease in a substantial proportion of patients.

Background & Aims: Photodynamic therapy (PDT) has been shown to be effective in the treatment of high-grade dysplasia (HGD)/mucosal carcinoma in Barrett's esophagus (BE). Substantial proportions of patients do not respond to PDT or progress to carcinoma despite PDT. The role of biomarkers in predicting response to PDT is unknown. We aimed to determine if biomarkers known to be associated with neoplasia in BE can predict loss of dysplasia in patients treated with ablative therapy for HGD/intramucosal cancer. Methods: Patients with BE and HGD/intramucosal cancer were studied prospectively from 2002 to 2006. Biomarkers were assessed using fluorescence in situ hybridization performed on cytology specimens, for region-specific and centromeric probes. Patients were treated with PDT using cylindric diffusing fibers (wavelength, 630 nm; energy, 200 J/cm fiber). Univariate and multiple variable logistic regression was performed to determine predictors of response to PDT. Results: A total of 126 consecutive patients (71 who underwent PDT and 55 patients who did not undergo PDT and were under surveillance, to adjust for the natural history of HGD), were included in this study. Fifty (40%) patients were responders (no dysplasia or carcinoma) at 3 months after PDT. On multiple variable analysis, P16 allelic loss (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.10–0.96) predicted decreased response to PDT. BE segment length (OR, 0.71; 95% CI, 0.59–0.85), and performance of PDT (OR, 7.17; 95% CI, 2.50–20.53) were other independent predictors of loss of dysplasia. Conclusions: p16 loss detected by fluorescence in situ hybridization can help predict loss of dysplasia in patients with BE and HGD/mucosal cancer. Biomarkers may help in the selection of appropriate therapy for patients and improve treatment outcomes.

Although EMR has been used for elimination of neoplasia in BE, the significance of positive carcinoma margins and depth of invasion on endoscopic resection pathology has not been assessed using a valid standard. The aim of this study was to assess the accuracy of tumor staging by EMR using esophagectomy as the standard.Medical records of patients, who underwent endoscopic resection for esophageal carcinoma or high-grade dysplasia in BE followed by esophagectomy, were reviewed. Data were abstracted from a prospectively maintained EMR database. Endosonography and endoscopic resection were performed by a single experienced endoscopist. Two experienced GI pathologists interpreted all histological results. Standard statistical tests were used to compare continuous and categorical variables.Twenty-five patients were included in the study. Three patients had mucosal carcinoma and 16 had submucosal carcinoma following endoscopic resection. Surgical pathology staging was consistent with preoperative EMR staging in all patients. No patient with negative mucosal resection margins had residual tumor at the resection site at esophagectomy. In patients with submucosal carcinoma, 8 had residual carcinoma at the EMR site at surgery and 5 patients had metastatic lymphadenopathy.Tumor staging using EMR pathology is accurate when compared with surgical pathology following esophagectomy. Negative margins on EMR pathology correlate with absence of residual disease at the EMR site at esophagectomy. Submucosal carcinoma on EMR specimens was associated with a high prevalence of residual disease at surgery (50%) and metastatic lymphadenopathy (31%).

Background & Aims: Recent studies have shown a survival advantage using photodynamic therapy (PDT) in patients with unresectable cholangiocarcinoma. Factors associated with increased survival after PDT are unknown. Methods: Twenty-five patients with cholangiocarcinoma who were treated with PDT at the Mayo Clinic Rochester from 1991 to 2004 were studied. Porfimer sodium (2 mg/kg) was administered intravenously to patients with Bismuth type I (3 patients), type III a/b (13 patients), and type IV (9 patients) tumors. Forty-eight hours later, PDT was administered using a 1.5- to 2.5-cm diffusing fiber that was advanced across the tumor by either retrograde (20 patients) or percutaneous (5 patients) cholangiography. Laser light was applied for a total energy of 180 J/cm2 in 1–3 applications. Patients received PDT treatments every 3 months. Plastic biliary stents (10–11.5 F) were inserted to decompress the biliary system after PDT. Survival analysis was performed using Kaplan–Meier curves and Cox proportional hazards models. Results: Patients were 64 (standard error of the mean, ±2.6) years of age; 20 (80%) were men. The median overall survival period was 344 days. The median survival period after PDT was 214 days. The 1-year survival rate was 30%. On multivariate analysis, the presence of a visible mass on imaging studies (hazard ratio, 3.55; 95% confidence interval, 1.21–10.38), and increasing time between diagnosis and PDT (hazard ratio, 1.13; 95% confidence interval, 1.02–1.25) predicted a poorer survival rate after PDT. A higher serum albumin level (hazard ratio, 0.16; 95% confidence interval, 0.04–0.59) predicted a lower mortality rate after PDT. Conclusions: Patients with unresectable cholangiocarcinoma without a visible mass may benefit from earlier treatment with PDT.

Background & Aims: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. Methods: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The κ statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. Results: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The κ statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The κ statistic for the margins of the EMR specimens was 0.80 (excellent agreement). Conclusions: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign–appearing lesions.

Background: Screening for Barrett's esophagus and esophageal adenocarcinoma is not currently advocated due to lack of data supporting its efficacy and concerns regarding expense. The cost of a screening program is primarily related to sedation and physician expertise. Performance of unsedated procedures by physician extenders (PEs) in the primary care setting could lead to an increased uptake of screening and decreased costs. Objective: Determine feasibility andmeasure learning curve while training PEs to independently perform transnasal endoscopy (TNE) screening for Barrett's esophagus. Methods: Two PEs underwent a one week structured didactic training program, which reviewed basic esophageal anatomy and pathology. This was followed by observation of nasopharyngoscopy procedures in ENT clinic to familiarize trainees with nasopharyngeal anatomy. To learn TNE, patients were then recruited with research consent among veterans undergoing sedated EGD in the Louis Stokes Veteran Affairs Medical Center in Cleveland, OH. Supervised TNE training procedures were assessed by two attendings who measured learning of individual technical and cognitive components of TNE and overall performance on a 9 point structured scale. Scores of 7 or more defined procedural competence. TNEs performed by two PEs were analyzed by method of cumulative summation (CUSUM) to construct individual learning curves. Results: Only 1 of 55 procedures could not be completed in the training phase. PE 1 and 2 could both identify anatomic landmarks including GE junction, diaphragm and gastric folds after 16 consecutive procedures and needed to complete 19 and 22 procedures, respectively to satisfactorily learn the technique of nasal intubation. Esophageal intubation was satisfactorily learned by PE 1 after 22 procedures whereas PE 2 is approaching but has not yet achieved a satisfactory score after 25 procedures. Figure 1 illustrates gradual improvement in overall performance based on number of completed procedures. Conclusion: A program to train PEs in the performance of TNE has been developed. PEs require a moderate number of supervised procedures to train in TNE. Esophageal intubation is the most challenging aspect of TNE.

Background: No-shows and appointment cancellations are especially salient to gastroenterology. Data shows that the incidence of colorectal cancer is down-trending, which correlates to increased colorectal cancer awareness and increase in the number of per capita screening colonoscopies. Patients lost to follow-up because of a no-show or cancellation (NS/C) might be at a higher risk of developing malignancy because of a missed screening opportunity. If particular patient demographics can be identified that are associated with NS/C, specific interventions can be proposed to capture those patients at possible increased risk. Aim: To determine if certain patient demographics contribute to the NS/C. Methods: A retrosepctive chart review using the Computerized Patient Records System (CPRS) at the Carl T.Hayden VA Medical Center in Phoenix, Arizona analyzed 17 weeks of data regarding NS/C. Data was obtained regarding the patient's: age, gender, new vs. follow appointment, type of procedure vs. clinic appointment, reason for appointment, and origin of the appointment, whether within the GI department or through open access primary care consultation. Results: 17 weeks of data were reviewed. A majority were male (92.2%). Ages ranged from 23-88 years and average age was 57.5 years old. 14.8% of patients were younger than 50. More NS/C were for follow-ups (55.8%) rather than new consults (44.2%). There were also more NS/C for colonoscopies (73.8%) than EGD's (24.1%) and paracentesis contributed to only 1.9% of the total. Appointments originating from outside the GI department were more likely to result in NS/C as 73.6% of those appointments originated from the PCP. Only 26.1% of NS/C originated from within the GI department. A specific analysis of coloscopy was made (table) revealing that 265 colonoscopies were performed. 19.3% of the NS/C colonoscopies scheduled for symptomatic complaints (pain, diarrhea, constipation, hematochezia) came from within the GI department while 80.7% came from the patient's PCP. This was supported by an overwhelming majority of /C screening and surveillance appointments that also came from outside the GI department (87.1%). Conclusions: This data illustrates that of patients who fail to keep their appointments, they are likely to be older than 50, with asymptomatic complaints, who are referred to the GI department by their PCP's. This is valuable information because patients lost in the NS/C process represent a missed opportunity for possible positive interventions including but not limited to the prevention of colorectal cancer. By identifying these variables, steps can be taken to minimize their contribution to the NS/C rate in the future.

G A A b st ra ct s high-risk, post-treated high-risk and post-treated low-risk patients (Fig. 1). For post-treated patients, a logistic regression model was developed using the most sensitive parameter of intra-nuclear uniformity, andwewere able to detect the high-risk patients with 88% sensitivity and 50% specificity. Conclusion: The optical analysis of gastric cardia can discriminate high-risk patients with esophageal dysplasia from low-risk patients after endoscopic therapy. It may serve as a novel biomarker for risk assessment or predicting the response to endoscopic therapy through examination of uninvolved gastric cardia. Given the decreased mucosal disruption with such sampling, this technique may also prove useful as a way to collect diagnostic information during the same endoscopy as an ablative session, thus decreasing the need for interval surveillance procedures. While these results are encouraging, future experiments using brushings from the GE junction may yield improved performance.

100.0%) and 85.7% (67.4-100.0%) respectively. Seven patients had gastro-duodenal lesions classified as probable or suspected source of bleeding. None had a positive FIT. Conclusion: the specificity of FIT for SB lesions classified as probable or suspected source of bleeding is quite high. Further studies are still needed to evaluate whether asymptomatic patients with positive FIT and non-explanatory colonoscopy should undergo further study of the small bowel

G A A b st ra ct s NSAID use and erosive esophagitis and/or esophageal strictures. Most studies were published 10 years ago and significant heterogeneity was seen between studies. Limited data suggest that use of NSAIDs was not significantly increased in patients with esophageal injury compared with controls, with a magnitude of effect size smaller than that reported with gastroduodenal ulcers. More evidence is required to have a clearer picture of esophageal injury caused by NSAIDs.

100.0%) and 85.7% (67.4-100.0%) respectively. Seven patients had gastro-duodenal lesions classified as probable or suspected source of bleeding. None had a positive FIT. Conclusion: the specificity of FIT for SB lesions classified as probable or suspected source of bleeding is quite high. Further studies are still needed to evaluate whether asymptomatic patients with positive FIT and non-explanatory colonoscopy should undergo further study of the small bowel

Background:Epithelial mesenchymal transition(EMT) is a crucial event in the metastatisis of carcinoma. EMT enables epithelial tumors to invade into the mesenchymal submucosa. The key feature of EMT is E-cadherin down-regulation. Snail, Slug and Twist are well recognized transcriptional factors as repressors of E-cadherin expression. Recently, a direct link has been shown between the EMT and cancer stem cell(CSC). CSC has the ability to self-renew and continually sustain tumorigenesis. Cells undergoing an EMT could be the precursors to metastatic carcinoma, perhaps as CSCs. CD133 is recognized marker for gastrointestinal CSCs. Aim:To characterize expressions of Snail, Slug, Twist and CD133 in the metastatic esophageal adenocarcinoma(EAC) in Barrett's esophagus(BE). Method:Formalin-fixed, paraffin embedded specimens of surgically treated early EAC were used. All slides were first reviewed by a well experienced GI pathologist, then were immunohistochemically stained for primary antibodies to Snail, Slug, Twist and CD133. We assessed if invading edges of tumor in the submucosa were stained for each antibody, and if there were differences of intensity of staining between in intramucosal cancer cells and in submucosal metastatic cells. The slides were scored by (1) intensity of staining (0=negative, 1=weak, 2=moderate, 3= intense);(2) percentage of epithelial cells staining (0=0-5%, 1=6-25%, 2=26-50%, 3=5175%, 4=76-100%);(3) percentage of invading cancer cells staining (same as epithelial cells). Cellular localization (nuclear, cytoplasm, cell surface) and uniformity (focal, general) were also assessed. Result:10 patients were analyzed. All four proteins were expressed in the cancers with uniform staining in both the mucosa and submucosa with Snail being more localized in the nucleus while Slug, Twist and CD133 were exclusively in the cytoplasm. Intensity of staining of metastatic cancer cells in submucosa was similar to those in the mucosa. Semi-quantitative scored analyses of Snail, Slug, Twist and CD133 for overall intensity were 2.5, 2.8, 1.9, and 2.4, respectively. For epithelial tumor cells, the scores were 4.0, 3.8, 3.3, and 3.2, respectively, whereas for invading metastatic cells, 4.0, 3.6, 3.1, and 3.6. Conclusion:This is the first report assessing the expression of known E-cadherin repressors, Snail, Slug, Twist and CSC marker, CD133 in the development of EAC in BE. All invading edges of tumor were found to abundantly express Snail, Slug, Twist and CD133 suggesting that unlike late staged cancers, early staged cancers are predominantly made of cells with metastatic potential which emphasizes the need to completely remove these early cancers.