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Background Dysphagia is the most common symptom in advanced esophageal cancer patients. Esophageal stent placement (SP) is a common palliation method but can be associated with significant morbidity. Limited data exist regarding the ability of spray cryotherapy (SC) prolong time to SP. Methods A Mayo Clinic (Rochester, MN) patient database was reviewed for cases with a SC indication of esophageal cancer palliation from 2007–2019. Procedures were performed using a liquid nitrogen SC system to apply 2–5 separate 20 second freeze and 60 second thaw cycles based on tumor characteristics. Primary outcome was time to subsequent palliative SP. Results Of 56 patients (71.4% male, mean age 77.8 ± 10.2 years) who underwent a total of 199 SC sessions (mean 3.6 ± 2.7, range 1–12 per patient), 41 had adenocarcinoma and 15 squamous cell carcinoma (SCC). Overall, 13 patients underwent subsequent SP within a mean duration of 15.7 ± 11.0 months over a mean follow-up duration of 25.6 ± 29.4 months. Treatment did produce stenosis in 16 patients, who required dilation within a mean period of 193.1 ± 294.1 days; notably, 10 patients had a history of preceding malignant strictures requiring dilation. Two patients experienced bleeding requiring transfusion, whereas 1 experienced perforation at the start of SC. Prior chemotherapy and/or radiation was not associated with developing an SC-related complication (risk ratio (RR) 1.5; 95% CI 0.6–3.7, P > 0.4). Conclusions SC appears to be an effective and safe modality to palliate esophageal cancer in appropriate candidates. Majority of patients who undergo SC avoid the need for future SP. If patients eventually require SP, they are able to, on average, defer stenting for >1 year from SC initiation. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Volumetric laser endomicroscopy (VLE) is used to identify Barrett's esophagus (BE) dysplasia. Selection of a dysplastic region of interest (ROI) can be challenging due to feature variability across a large amount of data. The degree of agreement among VLE users in selecting a ROI has not been studied. Methods: High‐definition videos that divided a VLE scan from 18 patients with biopsy‐proven BE dysplasia into 1‐cm segments were reviewed using a four‐quadrant grid superimposed for systematic interpretation. VLE scans were selected based on image quality and appropriate visualization of BE epithelium. Four experienced VLE users rated each quadrant as dysplastic or non‐dysplastic. For quadrants rated as dysplastic, reviewers selected a single timeframe with representative features. A high‐degree of agreement among reviewers was defined as ≥75% agreement on the quadrant diagnosis and ≥50% agreement on selected timeframe (±2 s). Results: Thirty‐one videos, each 32 s in length, comprising 124 quadrants were reviewed. There was high‐agreement among reviewers in 99 (80%) quadrants, of which 68 (69%) were rated as dysplastic. Compared with quadrants rated as non‐dysplastic, ROIs of quadrants rated as dysplastic contained a higher number of epithelial glands (12.7 vs 1.2, P < 0.001) with atypical architecture (54 vs 1, P < 0.001). A statistically significant difference was observed between the signal intensity profiles of quadrants rated as dysplastic and quadrants rated as non‐dysplastic (P = 0.004). Conclusion: This study highlights that experienced VLE users can identify ROIs with high‐degree of agreement. Selected ROIs contained VLE features associated with BE dysplasia. [ABSTRACT FROM AUTHOR]

Prediction of progression risk in Barrett's esophagus (BE) may enable personalized management. We aimed to assess the adjunct value of a tissue systems pathology test (TissueCypher) performed on paraffin-embedded biopsy tissue, when added to expert pathology review in predicting incident progression, pooling individual patient-level data from multiple international studies Demographics, clinical features, the TissueCypher risk class/score, and progression status were analyzed. Conditional logistical regression analysis was used to develop multivariable models predicting incident progression with and without the TissueCypher risk class (low, intermediate, high). Concordance (c-) statistics were calculated and compared with likelihood ratio tests to assess predictive ability of models. A risk prediction calculator integrating clinical variables and TissueCypher risk class was also developed. Data from 552 patients with baseline no (n = 472), indefinite (n = 32), or low-grade dysplasia (n = 48) (comprising 152 incident progressors and 400 non-progressors) were analyzed. A high-risk test class independently predicted increased risk of progression to high-grade dysplasia/adenocarcinoma (odds ratio, 6.0; 95% confidence interval, 2.9–12.0), along with expert confirmed low-grade dysplasia (odds ratio, 2.9; 95% confidence interval, 1.2–7.2). Model prediction of progression with the TissueCypher risk class incorporated was significantly superior than without, in the whole cohort (c-statistic 0.75 vs 0.68; P <.0001) and the nondysplastic BE subset (c-statistic 0.72 vs 0.63; P <.0001). Sensitivity and specificity of the high risk TissueCypher class were 38% and 94%, respectively. An objective tissue systems pathology test high-risk class is a strong independent predictor of incident progression in patients with BE, substantially improving progression risk prediction over clinical variables alone. Although test specificity was high, sensitivity was modest. [ABSTRACT FROM AUTHOR]

Barrett’s esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina’s Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Endoscopic mucosal resection (EMR) is an established technique for the management of Barrett's esophagus (BE). Although EMR is generally perceived to be a relatively safe procedure, the published data regarding EMR-related complications are variable and the expertise of those performing EMR is often not disclosed. Our aim was to determine the complication rates in a large cohort of patients who underwent EMR at a specialized BE unit.METHODS:A prospectively maintained database was reviewed for patients with BE who underwent EMR from January 1995 to August 2008. EMR was performed in patients with neoplastic appearing lesions. Bleeding, stricture, and perforation related to EMR were reviewed as the main outcome measurements.RESULTS:In all, 681 patients (83% male; mean age 70 years old) underwent a total of 1,388 endoscopic procedures and 2,513 EMRs. Median length of BE was 3.0 cm (interquartile range (IQR) 1-7). A single experienced endoscopist performed 99% of the EMR procedures. EMR was performed using commercially available EMR kits in 95% (77% cap-snare and 18% band-snare) and a variceal band ligation device in 5% of cases. No EMR-related perforations occurred during the study period. The rate of post-EMR bleeding was 1.2% (8 patients). Seven patients were successfully treated endoscopically and one needed surgery. The rate for symptomatic strictures after EMR was 1.0% (7 cases), and all of the cases did not involve intervening ablation therapies. All strictures were successfully treated with endoscopic dilation.CONCLUSIONS:This is the largest series reported to date on EMR in BE. In this large retrospective study, EMR for BE was associated with a low rate of complications for selected patients when performed by experienced hands. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is an established treatment for dysplastic Barrett's esophagus (BE). Although short-term end points of ablation have been ascertained, there have been concerns about recurrence of intestinal metaplasia (IM) after ablation. We aimed to estimate the incidence and identify factors that predicted the recurrence of IM after successful RFA. METHODS: We analyzed data from 592 patients with BE treated with RFA from 2003 through 2011 at 3 tertiary referral centers. Complete remission of intestinal metaplasia (CRIM) was defined as eradication of IM (in esophageal and gastroesophageal junction biopsy specimens), documented by 2 consecutive endoscopies. Recurrence was defined as the presence of IM or dysplasia after CRIM in surveillance biopsies. Two experienced gastrointestinal pathologists confirmed pathology findings. RESULTS: Based on histology analysis, before RFA, 71% of patients had high-grade dysplasia or esophageal adenocarcinoma, 15% had low-grade dysplasia, and 14% had nondysplastic BE. Of patients treated, 448 (76%) were assessed after RFA. Fifty-five percent of patients underwent endoscopic mucosal resection before RFA. The median time to CRIM was 22 months, with 56% of patients in CRIM by 24 months. Increasing age and length of BE segment were associated with longer times to CRIM. Twenty-four months after CRIM, the incidence of recurrence was 33%; 22% of all recurrences observed were dysplastic BE. There were no demographic or endoscopic factors associated with recurrence. Complications developed in 6.5% of subjects treated with RFA; strictures were the most common complication. CONCLUSIONS: Of patients with BE treated by REA, 56% were in complete remission after 24 months. However, 33% of these patients had disease recurrence within the next 2 years. Most recurrences were nondysplastic and endoscopicaUy manageable, but continued surveillance after RFA is essential. [ABSTRACT FROM AUTHOR]

Background and Aims Positron emission tomography with computed tomography ( PET/ CT) has been used to detect metastasis in the diagnosis of esophageal adenocarcinoma ( EAC). However, the utility of PET/ CT to assess primary tumor for endoscopic resectability and prognosis in early EAC remains unclear. We conducted a retrospective study to determine the association of PET/ CT findings with histopathological tumor invasion depth and survival outcomes. Methods EAC patients who underwent PET/ CT followed by endoscopic mucosal resection ( EMR) were included. Pathology on EMR and survival outcomes from a prospectively maintained database was retrieved. Two radiologists independently reviewed the PET/ CT using the following parameters: detection of malignancy, fluorodeoxyglucose ( FDG) uptake intensity, FDG focality, FDG eccentricity, esophageal thickness, maximal standard uptake value ( SUVmax), and SUVmax ratio (lesion/liver). Results There were 72 eligible patients: 42 (58.3%) had T1a lesions, and 30 (41.7%) had ≥ T1b. Only SUVmax ratio was associated with tumor invasion depth (odds ratio = 2.77, 95% confidence interval 1.26-7.73, P = 0.0075). Using a cut-off of 1.48, the sensitivity and specificity of SUVmax ratio for identification of T1a lesions were 43.3% and 80.9%, respectively. Adjusting the SUVmax ratio to 2.14, 16.7% (5/30) of ≥ T1b patients were identified without any false-positive cases. Multivariate analysis showed SUVmax ratio, Charlson comorbidity index, and esophagectomy were independent predictors for survival. Conclusions SUVmax ratio (lesion/liver) is more accurate in predicting endoscopic resectability and mortality for EAC than other PET/ CT parameters and appears promising as a useful adjunct to the current diagnostic work-up. [ABSTRACT FROM AUTHOR]

Summary: The progression of intestinal metaplasia to esophageal adenocarcinoma in patients with Barrett''s esophagus is partly driven by chromosomal alterations that activate oncogenes and inactivate tumor suppressor genes. The goal of this study was to determine how alterations of 4 frequently affected genes correlate with the range of histopathologic lesions observed in resected esophagi of patients with Barrett''s esophagus. Fluorescence in situ hybridization was used to assess 83 tissue sections from 10 Barrett''s esophagus esophagogastrectomy specimens for chromosomal alterations of 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2), and 20q13.2 (ZNF217). Histologic lesions assessed included gastric metaplasia (n = 8), intestinal metaplasia (n = 43), low-grade dysplasia (n = 28), high-grade dysplasia (n = 25), and adenocarcinoma (n = 16). Histologic maps showing the correlation between fluorescence in situ hybridization abnormalities and corresponding histology were created for all patients. Chromosomal abnormalities included 9p21 loss, single locus gain, and polysomy. A greater number of chromosomal alterations were detected as the severity of histologic diagnosis increased from intestinal metaplasia to adenocarcinoma. All patients had alterations involving the CDKN2A gene. CDKN2A loss was the only abnormality detected in 20 (47%) of 43 areas of intestinal metaplasia. Polysomy, the most common abnormality in dysplastic epithelium and adenocarcinoma, was observed in 16 (57%) of 28 low-grade dysplasia, 22 (88%) of 25 high-grade dysplasia, and 16 (100%) of 16 adenocarcinoma. The findings of this study improve our understanding of the role that chromosomal instability and alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett''s esophagus. [Copyright &y& Elsevier]

Background & Aims: Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett''s esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE. Methods: We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events. Results: After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan–Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years). Conclusions: In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years. [Copyright &y& Elsevier]

Background: Despite many attempts to establish pre-treatment prognostic markers to understand the clinical biology of esophageal adenocarcinoma (EAC), validated clinical biomarkers or parameters remain elusive. We generated and analyzed tumor transcriptome to develop a practical biomarker prognostic signature in EAC. Methodology/Principal Findings: Untreated esophageal endoscopic biopsy specimens were obtained from 64 patients undergoing surgery and chemoradiation. Using DNA microarray technology, genome-wide gene expression profiling was performed on 75 untreated cancer specimens from 64 EAC patients. By applying various statistical and informatical methods to gene expression data, we discovered distinct subgroups of EAC with differences in overall gene expression patterns and identified potential biomarkers significantly associated with prognosis. The candidate marker genes were further explored in formalin-fixed, paraffin-embedded tissues from an independent cohort (52 patients) using quantitative RT-PCR to measure gene expression. We identified two genes whose expression was associated with overall survival in 52 EAC patients and the combined 2-gene expression signature was independently associated with poor outcome (P<0.024) in the multivariate Cox hazard regression analysis. Conclusions/Significance: Our findings suggest that the molecular gene expression signatures are associated with prognosis of EAC patients and can be assessed prior to any therapy. This signature could provide important improvement for the management of EAC patients. [ABSTRACT FROM AUTHOR]

It may be questioned whether photodynamic therapy is still relevant for practicing gastroenterologists as other types of therapy have currently gained momentum. Important aspects of photodynamic therapy that continue its development are its intrinsic applicability to the luminal gastrointestinal tract where often there are areas of mechanical narrowing, unusual topography, and difficult accessibility where a modality that does not require contact or optical visualization has advantages. Although not used as often in the upper gastrointestinal tract for its original approved indications, such as esophageal cancer or Barrett''s esophagus, its value in biliary lesions appears to be well substantiated. In this article, we will review its current application in the upper gastrointestinal tract. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Background: Currently, histology is used as the endpoint to define success with photodynamic therapy (PDT) in patients with high-grade dysplasia (HGD). Recurrences despite 'successful' ablation are common. The role of biomarkers in assessing response to PDT remains undefined. The objectives of the current study were 1) to assess biomarkers in a prospective cohort of patients with HGD/mucosal cancer before and after PDT and 2) to correlate biomarker status after PDT with histology.Methods: Patients who underwent PDT for HGD/mucosal cancer were studied prospectively. All patients underwent esophagogastroduodenoscopy, 4-quadrant biopsies every centimeter, endoscopic mucosal resection of visible nodules, and endoscopic ultrasound. Cytology samples were obtained by using standard cytology brushes. Biomarkers were assessed by using fluorescence in situ hybridization (FISH). The biomarkers that were assessed included loss of 9p21 (site of the p16 gene) and 17p13.1 (site of the p53 gene) loci; gains of the 8q24(c-myc), 17q (HER2-neu), and 20q13 loci; and multiple gains. Patients received PDT 48 hours after the administration of sodium porfimer. Demographic and clinical variables were collected prospectively. Patients were followed with endoscopy and repeat cytology for biomarkers. The McNemar test was used to compare biomarker proportions before and after PDT.Results: Thirty-one patients were studied. The median patient age was 66 years (interquartile range [IQR], 56-73 years), and 28 patients (88%) were men. The mean Barrett segment length was 5 cm (standard error of the mean, 0.5 cm). Post-PDT biomarkers were obtained after a median duration of 9 months (IQR, 3-12 months). There was a statistically significant decrease in the proportion of several biomarkers assessed after PDT. Six patients without HGD after PDT still had positive FISH results for 1 or more biomarkers: of these, 2 patients (33%) developed recurrent HGD.Conclusions: In this initial study, histologic downgrading of dysplasia after PDT was associated with the loss of biomarkers that have been associated with progression of neoplasia in Barrett esophagus. Patients with persistently positive biomarkers appeared to be at a higher risk of recurrent HGD. These findings should be confirmed in a larger study. [ABSTRACT FROM AUTHOR]

The article provides information on the revision made on the 2008 Guidelines for the Diagnosis, Surveillance and Therapy of Barrett's Esophagus. The guidelines for the diagnosis, surveillance and therapy of Barrett's esophagus were originally published by the American College of Gastroenterology in 1998 and updated in 2002. These and other guidelines undergo periodic review.

The treatment of early neoplastic lesions in Barrett’s esophagus may require a combination of therapies. Although both photodynamic therapy and mucosal resection have been demonstrated to have efficacy in treating early cancers and high dysplasia, the difficulty has been that removal of the most neoplastic visible lesions still permits unstable mucosa behind that may be histologically more benign. Although it is assumed that nondysplastic Barrett’s mucosa has very little risk of further evolution to high-grade dysplasia or cancer, this has been taken in the context of patients who have never developed high-grade lesions. Multiple case series have shown that leaving behind Barrett’s mucosa with or without dysplasia after removal of an early cancer leaves patients at increased risk of re-development of cancer. The treatment of these lesions is controversial. Further ablation of this residual tissue has been the preferred strategy by several experts with the use of extensive mucosectomy techniques or combining mucosectomy techniques with ablative strategies such as photodynamic therapy. Extensive mucosectomy would seem to have the theoretical advantage of completing eliminating neoplastic tissue, although this is difficult to achieve with current techniques. Photodynamic therapy can also be used in conjunction with mucosectomy with good results in small case series. Other possible combination therapies might include the use of chemoprevention agents, which is appealing but unproven at the present time. [Copyright &y& Elsevier]

It is a challenge to detect dysplasia in Barrett's esophagus (BE) and esophageal adenocarcinomas (EACs) are missed in 25%–33% of cases. The neoplasia detection rate (NDR), defined as the rate of high-grade dysplasia (HGD) or EAC detection during initial surveillance endoscopy, has been proposed as a quality metric for endoscopic evaluation of patients with BE. However, current estimates are from referral center cohorts, which might overestimate NDR. Effects on rates of missed dysplasia are also unknown. We analyzed data from a large cohort of patients with BE to estimate the NDR and factors associated with it, and assess the effects of the NDR on the rate of missed dysplasia. We analyzed data from 1066 patients in the Rochester Epidemiology Project-linked medical record system, a population-based cohort of patients with BE (confirmed by review of the endoscopic and histologic reports) from 11 southeastern Minnesota counties from 1991 through 2019. Biopsies reported to contain dysplasia were confirmed by expert gastrointestinal pathologists. The NDR was calculated as the rate of HGD or EAC detected by histologic analyses of biopsies collected during the first surveillance endoscopy. Patients without HGD or EAC at their initial endoscopy (n = 391) underwent repeat endoscopy within 12 months; HGD or EAC detected at the repeat endoscopy were considered to be missed on index endoscopy. Factors associated with NDR and missed dysplasia were identified using univariate and multivariate logistic regression models. The NDR was 4.9% (95% CI, 3.8–6.4); 3.1% of patients had HGD, 1.8% had EAC, and 10.6% had low-grade dysplasia. Factors associated with higher rates of detection of neoplasia included older age, male sex, smoking, increasing length of BE, and surveillance endoscopies by gastroenterologists. This NDR was associated with a substantially lower rate of missed dysplasia (13%). In an analysis of 1066 patients with BE in a population-based cohort, we found a lower NDR and lower rate of missed dysplasia than previously reported. NDR may have value as a quality metric in BE surveillance if validated in other cohorts. [ABSTRACT FROM AUTHOR]

The incidence of esophageal adenocarcinoma (EAC) has increased over the past decades. It is unclear if this increase is the result of a new cancer phenotype or an increase in risk factors for EAC. We aimed to compare risk factors, the proportions of intestinal and nonintestinal phenotypes of EAC, and survival times of patients during the 2009 to 2012 time period vs the 1996 to 1997 time period. We performed a retrospective single-center cohort study of 829 patients with EAC from the time periods of 1996 to 1997 and 2009 to 2012. Baseline characteristics were compared using χ2 analysis for categoric variables and the Student t test for continuous variables. The Cox proportional hazards model was used to compare 5-year survival. We included 149 patients from the 1996 to 1997 time period and 680 patients from the 2009 to 2012 time period. There was no significant difference between the cohorts in terms of age at cancer presentation, sex, or history of smoking (P >.05). Gastroesophageal reflux symptoms were absent in almost half of the patients from each time period (P =.46). Intestinal metaplasia was identified in esophageal tumor tissues from 48.3% of patients with EAC in the 1996 to 1997 time period and in 49.9% of patients in the 2009 to 2012 time period (P =.45). Patients from each time period presented with similar-stage cancer (P =.25), most at stage III (43% in the 1996–1997 period and 37.8% in the 2009–2012 period). Having EAC during the period of 1996 to1997 was associated with an increased risk of death (hazard ratio, 1.6; 95% CI, 1.3–2.0; P =.001), compared with the 2009 to 2012 time period, in a univariate model (adjusted hazard ratio, 1.7; 95% CI, 1.4–2.1; P <.001) after we controlled for sex, age at diagnosis, tumor stage, and presence of intestinal metaplasia. In a comparison of patients with EAC from the time periods of 1996 to 1997 vs 2009 to 2012, we found similar and persistent proportions of tumor phenotypes, characterized by a lack of intestinal metaplasia or heartburn symptoms. The lack of symptoms could contribute to our continued inability to identify incident cancers and/or improve patient survival. [ABSTRACT FROM AUTHOR]

The article considers the application of endoscopy for treating Barrett's esophagus and early esophageal cancer. One of the opportunities offered by Barrett's esophagus to the endoscopically study neoplasia in the esophagus is the impact of chronic inflammatory change caused by reflux of acid and bile into the distal esophagus. Endoscopy is centered in the termination of existing metaplastic tissue through the use of thermal or photochemical therapies that remove the mucosa.

Background & Aims A proportion of patients with Barrett’s esophagus (BE) are diagnosed with esophageal adenocarcinoma (EAC) within 1 year of an endoscopic examination that produced negative findings. These cases of missed cancers have not been well studied, despite current surveillance strategies for BE. We performed a systematic review and meta-analysis to determine the magnitude of missed EAC in cohorts of patients with BE. Methods We searched MEDLINE, EMBASE, and Web of Science from their inception to May 31, 2015 to identify cohort studies of adults with BE (baseline nondysplastic BE ± BE with low-grade dysplasia) and at least a 3-year follow-up period, providing data on missed and incident EACs (diagnosed within 1 year and diagnosed more than 1 year after the initial endoscopy in which BE was diagnosed, respectively). The main outcome measure was pooled proportion of missed and incident EACs (of all EACs detected after initial endoscopy) among BE cohorts, using a random effects model. Results In a meta-analysis of 24 studies reporting on 820 missed and incident EACs, 25.3% were classified as missed (95% confidence interval: 16.4%–36.8%) and 74.7% as incident EACs (95% CI: 63.2%–83.6%), although there was substantial heterogeneity among studies (I 2 = 74%). When the analysis was restricted to nondysplastic BE cohorts (15 studies), 23.9% of EACs were classified as missed (95% confidence interval: 15.3%–35.4%; I 2 = 0%). In a meta-analysis of 10 studies with follow-up periods of ≥5 years (a total of 239 EACs), 22.0% were classified as missed (95% confidence interval: 8.7%–45.5%), with substantial heterogeneity (I 2 = 68%). Conclusions Among adults with nondysplastic BE (or BE with low-grade dysplasia) at their index endoscopy and at least a 3-year follow-up period, 25% of EACs are diagnosed within 1 year after the index endoscopy. Additional resources should be allocated to detect missed EAC. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a letter regarding the risk of cancer in a columnar-lined esophagus without intestinal metaplasia by Clive Kelty that appears in the current issue.

Background & Aims Barrett's esophagus (BE) with low-grade dysplasia (LGD) can progress to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) has been shown to be an effective treatment for LGD in clinical trials, but its effectiveness in clinical practice is unclear. We compared the rate of progression of LGD after RFA with endoscopic surveillance alone in routine clinical practice. Methods We performed a retrospective study of patients who either underwent RFA (n = 45) or surveillance endoscopy (n = 125) for LGD, confirmed by at least 1 expert pathologist, from October 1992 through December 2013 at 3 medical centers in the United States. Cox regression analysis was used to assess the association between progression and RFA. Results Data were collected over median follow-up periods of 889 days (interquartile range, 264−1623 days) after RFA and 848 days (interquartile range, 322−2355 days) after surveillance endoscopy ( P = .32). The annual rates of progression to HGD or EAC were 6.6% in the surveillance group and 0.77% in the RFA group. The risk of progression to HGD or EAC was significantly lower among patients who underwent RFA than those who underwent surveillance (adjusted hazard ratio = 0.06; 95% confidence interval: 0.008−0.48). Conclusions Among patients with BE and confirmed LGD, rates of progression to a combined end point of HGD and EAC were lower among those treated with RFA than among untreated patients. Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for LGD. [ABSTRACT FROM AUTHOR]

Background & Aims Superficial (T1) esophageal adenocarcinoma (EAC) commonly is treated by endoscopic resection, yet little is known about factors that predict outcomes of this approach. We assessed clinical and histologic variables associated with the overall survival times of patients with T1 EAC who received therapy. Methods In a retrospective analysis, we collected data from patients who underwent endoscopic mucosal resection (EMR) for T1 EAC (194 patients with T1a and 75 patients with T1b) at the Mayo Clinic, from 1995 through 2011. EMR specimens were reviewed systematically for depth of invasion, presence of lymphovascular invasion, grade of differentiation, and status of resection margins. Kaplan–Meier curves and proportional hazards regression models were used in statistical analyses. Results Demographic characteristics were similar between patients with T1a and T1b EAC. Overall survival at 5 years after EMR was 74.4% for patients with T1a (95% confidence interval [CI], 67.6%−81.8%) and 53.2% for patients with T1b EAC (95% CI, 40.3%–70.1%). Of surviving patients with T1a EAC, 94.1% remained free of cancer (95% CI, 89.8%–98.5%), and 94.7% of surviving patients with T1b EAC remained free of cancer (95% CI, 85.2%−100%). A multivariable model associated older age (per 10-year increment), evidence of lymphovascular invasion, and deep margin involvement with reduced overall survival in patients with T1 EAC. Conclusions Systematic assessment of EMR specimens can help predict mortality and potentially guide treatment options for patients with T1 EAC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]