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INTRODUCTION: Minimally invasive tests for Barrett's esophagus (BE) detection have raised the prospect of broader nonreflux-based testing. Cost-effectiveness studies have largely studied men aged 50 years with chronic gastroesophageal reflux disease (GERD) symptoms. We evaluated the comparative cost effectiveness of BE screening tests in GERD-based and GERD-independent testing scenarios. METHODS: Markov modeling was performed in 3 scenarios in 50 years old individuals: (i) White men with chronic GERD (GERD-based); (ii) GERD-independent (all races, men and women), BE prevalence 1.6%; and (iii) GERD-independent, BE prevalence 5%. The simulation compared multiple screening strategies with no screening: sedated endoscopy (sEGD), transnasal endoscopy, swallowable esophageal cell collection devices with biomarkers, and exhaled volatile organic compounds. A hypothetical cohort of 500,000 individuals followed for 40 years using a willingness to pay threshold of $100,000 per quality-adjusted life year (QALY) was simulated. Incremental cost-effectiveness ratios (ICERs) comparing each strategy with no screening and comparing screening strategies with each other were calculated. RESULTS: In both GERD-independent scenarios, most non-sEGD BE screening tests were cost effective. Swallowable esophageal cell collection devices with biomarkers were cost effective (

Introduction Esophageal epidermoid metaplasia (EEM) is a rare disease. Methods Patients with EEM diagnosed between 2014 and 2020 were reviewed. Results Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy. Discussion EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.

INTRODUCTION It is assumed that screening risk factors for Barrett's esophagus (BE) and prevalent esophageal adenocarcinoma (EAC) are the same. METHODS A matched case-control study comparing risk factors between EAC and BE was performed. RESULTS In 1,356 patients (678 with EAC and 678 with BE), heartburn (52.7%), diabetes, hyperlipidemia, hypertension, nonalcoholic steatohepatitis, and metabolic syndrome were less common in EAC (52.7, 29.2, 45.7, 48.2, 12, and 28.5%, resp.) compared with BE (84.5, 37.6, 82.2, 64.6, 18.4, and 44.1%, P < 0.01). Mean alanine aminotransferase and HgA1c levels were also significantly lower in EAC compared with BE. DISCUSSION Optimal strategies for screening for prevalent EAC may be different than that for BE.

Introduction Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay. Methods BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation. Results Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4-9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%-96%) and 94% (95% confidence interval 87%-98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median [interquartile range] tolerability 2 [0, 4] on 10 scale grading), and 95% preferred SOS over endoscopy. Discussion Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.

Adjustments for lead and length time bias has been used when examining apparent survival advantages from screening procedures. However, these estimates depend on several assumptions and are modeled from malignancies that are fairly common and large cohorts are available. In smaller retrospective cohorts, adjustments themselves may be based on estimates that may not be biological nor statistically accurate, which can lead to divergent results as has been found in several recent studies of screening in Barrett's esophagus. Only a prospective randomized controlled trial can really determine the benefit though this may not feasible.

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. Significant advances have occurred in the area of Barrett’s esophagus over the past four years leading to another revision of the prior guidelines. These advances include the potential use of esophageal capsule endoscopy for the diagnosis and screening of Barrett’s esophagus, data regarding the outcome of low-grade dysplasia, the treatment of high-grade dysplasia using photodynamic therapy, and the development of new ablation techniques such as radiofrequency ablation. These guidelines are intended to be applied by physicians who see Barrett’s esophagus patients and are intended to indicate a preferred, but certainly not the only, acceptable approach. Physicians need to choose the course best suited to the individual patient and to the variables that exist at the time of decision making. The guidelines are for adult patients with the diagnosis of Barrett’s esophagus, as defined herein. Both these and the original guidelines were developed under auspices of the American College of Gastroenterology and the Practice Parameters Committee and approved by the Board of Trustees. The world literature was reviewed extensively for the original guidelines and once again reviewed using the National Library of Medicine database. Search terms used included Barrett’s esophagus, esophageal neoplasm, esophagus, intestinal metaplasia, esophageal diseases, and adenocarcinoma, all appropriate studies and any additional ones found in reference to these papers were obtained and reviewed. Evidence was available from a hierarchy of trials and randomized controlled trials were given the greatest weight. Abstracts presented at national and international meetings were only used when unique data from ongoing trials were presented. When scientific data were lacking, recommendations are based on expert opinion. The recommendations made are based on the level of evidence found. Grade A recommendations imply that there is consistent level 1 evidence (randomized controlled trials), Grade B indicates that the evidence would be level 2 or 3 which are cohort studies or case control studies. Grade C recommendations are based on level 4 studies meaning case series or poor quality cohort studies, and Grade D recommendations are based on level 5 evidence meaning expert opinion.

Celiac plexus neurolysis and block are considered safe but provide limited pain relief. Standard techniques target the region of the celiac plexus but do not attempt injections directly into celiac ganglia. The recent recognition that celiac ganglia can be visualized by endoscopic ultrasound (EUS) now allows direct injection into celiac ganglia for neurolysis (CGN) and block (CGB).To determine the safety and initial efficacy (at 2-4 wk) of direct ganglia injection in patients with moderate to severe pain secondary to unresectable pancreatic carcinoma or chronic pancreatitis.An EUS database was reviewed to identify patients undergoing CGN and CGB. Data were retrieved from the medical records and phone follow-up.Thirty-three patients underwent 36 direct celiac ganglia injections for unresectable pancreatic cancer (CGN N = 17, CGB N = 1) or chronic pancreatitis (CGN N = 5, CGB N = 13) with bupivacaine (0.25%) and alcohol (99%) for CGN, or Depo-Medrol (80 mg/2 cc) for CGB. Cancer patients reported pain relief in 16/17 (94%) when alcohol was injected and 0/1 (00%) when steroid was injected. For chronic pancreatitis, 4/5 (80%) who received alcohol reported pain relief versus 5/13 (38%) receiving steroids. Thirteen (34%) patients experienced initial pain exacerbation, which correlated with improved therapeutic response (P0.05). Transient hypotension and diarrhea developed in 12 and 6 patients, respectively.Initial experience suggests that EUS-guided direct celiac ganglion block or neurolysis is safe. Alcohol injection into ganglia appears to be effective in both cancer and chronic pancreatitis. Prospective trials are needed to confirm the efficacy of this new approach.

Improvements in narrow band imaging (NBI) may provide an improved view of colonic mucosa for detection of polyps and adenomas. In this issue, Leung et al. report findings to suggest that this next-generation NBI technology is superior to conventional high-definition white light endoscopy in polyp detection. These findings are based on brighter illumination, which has been a problem with older generations of NBI, which did not increase polyp detection but were useful for polyp characterization. Although these findings are very promising for this new role of second-generation NBI in polyp detection, the study must be viewed with consideration of the history of the older NBI system, the analysis of which through multiple positive and negative studies ultimately led to the conclusion that it was not beneficial for detection.

Recent studies have demonstrated high esophageal eosinophil counts in patients with GERD similar to eosinophilic esophagitis (EoE) yet the frequency of esophageal eosinophilia in GERD is unknown. Our aim was to determine the prevalence of dense esophageal eosinophilia in patients with Barrett's esophagus as a manifestation of GERD.The Mayo Clinic pathology database was reviewed for patients diagnosed with Barrett's esophagus from January to December 2008 with squamous mucosa obtained during endoscopic surveillance. Clinical, endoscopic, and histologic findings were reviewed. Patients with ≥15 eosinophils per high powered field were identified and compared to those without esophageal eosinophilia.Two hundred patients with Barrett's esophagus and squamous tissue obtained at the time of biopsy were identified. Fourteen of the 200 patients (7%) had ≥15 eosinophils per high powered field. Demographics, symptoms, and proton pump inhibitor therapies were similar between those with and without esophageal eosinophilia. Endoscopic features suggestive of EoE were found in the squamous mucosa of 2 patients with and 7 patients without esophageal eosinophilia. Use of photodynamic, radiofrequency ablation, or monopolar electrocoagulation therapy for ablation of Barrett's mucosa was not associated with a higher rate of esophageal eosinophilia. Basal cell hyperplasia, papillary elongation, and spongiosis occurred frequently in association with esophageal eosinophilic infiltration.High esophageal eosinophil counts were found in 7% of this cohort of 200 patients with Barrett's esophagus and likely underestimates prevalence. The finding of esophageal eosinophilia in this cohort was independent of proton pump inhibitor use, features of EoE, or endoscopic therapy for Barrett's esophagus. Further studies are needed to assess if these findings are applicable to all patients with GERD.

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.

We have summarized the characteristics of the clinically useful or potentially useful biomarkers in a number of GI cancers. This field is growing, and the predictive and diagnostic value of the biomarkers as a measure of carcinogenesis is still in evolution. It is essential for the clinician to have an understanding of the basic molecular biology behind GI cancers because, in the future, many clinicians will be routinely ordering biomarker testing as part of patient screening. The biomarkers in GI cancers are useful not only for screening, diagnosis, and prognosis but also for prediction of the response to mechanism-based interventions, such as chemoprevention. Ongoing assessment of these diagnostic and predictive factors will probably lead to a change in the current staging of many GI cancers.

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%).

TO THE EDITOR: We appreciate the comments of Dr. Kelty and are aware of his retrospective study. The points raised by Dr. Kelty are addressed in the guidelines as we acknowledge that there is a lack of consensus on the diagnosis of Barrett's esophagus. The guidelines state that a recent retrospective study has found that if eight biopsies are taken in a columnar esophageal segment, 68% of patients can be found to have goblet cells versus only 35% of those with that had only four biopsies (1, 2). The retrospective study of Dr. Kelty's had a median of only four biopsies in both the intestinal metaplasia and glandular mucosa group, which raised questions in our minds on the ability of this study to answer the question of the cancer risk in those with and without goblet cells given that up to half of those classified as not having intestinal metaplasia may well have had goblet cells (3). Furthermore, retrospective studies based on histology have clearly found that the presence of intestinal metaplasia correlates with risk of progression to dysplasia as opposed to those glandular mucosal without intestinal metaplasia (4).

Endoscopic appearance and extent of high-grade dysplasia in Barrett's esophagus can predict the presence of cancer at esophagectomy

Can endoscopic mucosal resection completely remove cancer or dysplasia in Barretts esophagus?