Comparative Outcomes of Cap Assisted Endoscopic Resection and Endoscopic Submucosal Dissection in Dysplastic Barrett's Esophagus.

BACKGROUND & AIMS: Endoscopic resection is an important component of the endoscopic treatment of Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma. Endoscopic resection can be performed by cap-assisted endoscopic mucosal resection (cEMR) or endoscopic submucosal dissection (ESD). We compared the histologic outcomes of ESD vs cEMR, followed by ablation. METHODS: We queried a prospectively maintained database of all patients undergoing cEMR and ESD followed by ablation at our institution from January 2006 to March 2020 and abstracted relevant demographic and clinical data. Our primary outcomes included the rate of complete remission of dysplasia (CRD): absence of dysplasia on surveillance histology, and complete remission of intestinal metaplasia (CRIM): absence of intestinal metaplasia. Our secondary outcome included complication rates. RESULTS: We included 537 patients in the study: 456 underwent cEMR and 81 underwent ESD. The cumulative probabilities of CRD at 2 years were 75.8% and 85.6% in the cEMR and ESD groups, respectively (P < .01). Independent predictors of CRD were as follows: ESD (hazard ratio [HR], 2.38; P < .01) and shorter BE segment length (HR, 1.11; P < .01). The cumulative probabilities of CRIM at 2 years were 59.3% and 50.6% in the cEMR and ESD groups, respectively (P > .05). The only independent predictor of CRIM was a shorter BE segment (HR, 1.16; P < .01). CONCLUSIONS: BE patients with dysplasia or intramucosal adenocarcinoma undergoing ESD reach CRD at higher rates than those treated with cEMR, although CRIM rates at 2 years and complication rates were similar between the 2 groups.

Neoplasia Detection Rate in Barrett's Esophagus and Its Impact on Missed Dysplasia: Results from a Large Population-Based Database.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Effects of Central Obesity on Esophageal Epithelial Barrier Function.

INTRODUCTION: We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER). METHODS: Thirty-eight participants were divided into 4 groups: Obesity-/GER-, Obesity+/GER-, Obesity-/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured. RESULTS: The Obesity+/GER- group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity-/GER + and Obesity+/GER+ patients. DISCUSSION: Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.

Outcomes of radiofrequency ablation by manual versus self-sizing circumferential balloon catheters for the treatment of dysplastic Barrett's esophagus: a multicenter comparative cohort study.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is the preferred ablative modality for treating dysplastic Barrett's esophagus. The recently introduced self-sizing circumferential ablation catheter eliminates the need for a sizing balloon. Although it enhances efficiency, outcomes have not been compared with the previous manual-sizing catheter. We evaluated the comparative safety and efficacy of these 2 ablation systems in a large, multicenter cohort. METHODS: Patients undergoing RFA at 3 tertiary care centers from 2005 to 2018 were included. Circumferential RFA was performed in a standard fashion, followed by focal RFA as needed. Outcomes were compared between the self-sizing and manual-sizing groups. The primary outcome was the rate of adverse events, including strictures, perforation, and bleeding. Secondary outcomes were procedure time and treatment efficacy, as assessed by rates and time to complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM). RESULTS: Three hundred eighteen patients were included, 90 (28.3%) treated with the self-sizing catheter and 228 (71.7%) with the manual-sizing catheter. Twenty-one patients (6.6%) developed strictures (8 [8.9%] in the self-sizing group and 13 [5.7%] in the manual-sizing group, P = .32). Of the self-sizing strictures, 75% occurred at the 12J dose before widespread adoption of the current 10J treatment standard. One patient developed bleeding, and no perforations were encountered. Procedure time was significantly shorter in the self-sizing group. No significant differences were observed in rates of and time to CE-D and CE-IM. CONCLUSIONS: These findings suggest that both systems are comparable in safety and efficacy. The use of the self-sizing system may enhance the efficiency of RFA for treating dysplastic Barrett's esophagus.

Development and Pilot Testing of Decision Aid for Shared Decision Making in Barrett's Esophagus With Low-Grade Dysplasia.

GOALS: To develop an encounter decision aid [Barrett's esophagus Choice (BE-Choice)] for patients and clinicians to engage in shared decision making (SDM) for management of BE with low-grade dysplasia (BE-LGD) and assess its impact on patient-important outcomes. BACKGROUND: Currently, there are 2 strategies for management of BE-LGD-endoscopic surveillance and ablation. SDM can help patients decide on their preferred management option. STUDY: Phase-I: Patients and clinicians were engaged in a user-centered design approach to develop BE-Choice. Phase-I included review of evidence on BE-LGD management, observation of usual care (UC), creation, field-testing, and iterative development of BE-Choice in clinical settings. Phase-II: Impact of BE-Choice on patient-important outcomes (patient knowledge, decisional conflict, and patient involvement in decision making) was assessed using a controlled before-after study design (UC vs. BE-Choice). RESULTS: Phase-I: Initial prototype was designed with observation of 8 clinical encounters. With field-testing, 3 successive iterations were made before finalizing BE-Choice. BE-Choice was paper based and fulfilled the qualifying criteria of International patient decision aid standards. Phase II: 29 patients were enrolled, 8 to UC and 21 to BE-Choice. Compared with UC, use of BE-Choice improved patient knowledge (90.4% vs. 70.5%; P=0.03), decisional comfort (89.6 vs. 71.9; P=0.01), and patient involvement (OPTION score: 27.1 vs. 19.2; P=0.01). CONCLUSIONS: BE-Choice is a feasible and effective decision aid to promote SDM in the management of BE-LGD. On pilot testing, BE-Choice had promising impact on patient-important outcomes. A larger multicenter trial is needed to confirm our results and promote widespread use of BE-Choice.

Accurate Nonendoscopic Detection of Barrett's Esophagus by Methylated DNA Markers: A Multisite Case Control Study.

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.

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND AND AIMS: The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival. METHODS: Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival. RESULTS: One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival. CONCLUSIONS: In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.

Timeline and location of recurrence following successful ablation in Barrett's oesophagus: an international multicentre study.

OBJECTIVE: Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett's oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines. DESIGN: Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies. RESULTS: 594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4-4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI -7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia). CONCLUSIONS: BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.

Highly Discriminant Methylated DNA Markers for the Non-endoscopic Detection of Barrett's Esophagus.

BACKGROUND: Minimally invasive methods have been described to detect Barrett's esophagus (BE), but are limited by subjectivity and suboptimal accuracy. We identified methylated DNA markers (MDMs) for BE in tissue and assessed their accuracy on whole esophagus brushings and capsule sponge samples. METHODS: Step 1: Unbiased whole methylome sequencing was performed on DNA from BE and normal squamous esophagus (SE) tissue. Discriminant MDM candidates were validated on an independent patient cohort (62 BE cases, 30 controls) by quantitative methylation specific PCR (qMSP). Step 2: Selected MDMs were further evaluated on whole esophageal brushings (49 BE cases, 36 controls). 35 previously sequenced esophageal adenocarcinoma (EAC) MDMs were also evaluated. Step 3: 20 BE cases and 20 controls were randomized to swallow capsules sponges (25 mm, 10 pores or 20 pores per inch (ppi)) followed endoscopy. DNA yield, tolerability, and mucosal injury were compared. Best MDM assays were performed on this cohort. RESULTS: Step 1: 19 MDMs with areas under the ROC curve (AUCs) >0.85 were carried forward. Step 2: On whole esophageal brushings, 80% of individual MDM candidates showed high accuracy for BE (AUCs 0.84-0.94). Step 3: The capsule sponge was swallowed and withdrawn in 98% of subjects. Tolerability was superior with the 10 ppi sponge with minimal mucosal injury and abundant DNA yield. A 2-marker panel (VAV3 + ZNF682) yielded excellent BE discrimination (AUC = 1). CONCLUSIONS: Identified MDMs discriminate BE with high accuracy. BE detection appears safe and feasible with a capsule sponge. Corroboration in larger studies is warranted. ClinicalTrials.gov number NCT02560623.

Comparative Assessment of Patient Preferences and Tolerability in Barrett Esophagus Screening: Results From a Randomized Trial.

GOALS: To determine patient preference for the Barrett esophagus (BE) screening techniques. BACKGROUND: Sedated esophagogastroduodenoscopy (sEGD) and unsedated transnasal endoscopy (uTNE) are both potential techniques for BE screening. However, systematic assessment of patient preference for these 2 techniques is lacking. As part of a comparative effectiveness randomized trial of BE screening modalities, we measured short-term patient preferences for the following approaches: in-clinic uTNE (huTNE), mobile-based uTNE (muTNE), and sEGD using a novel assessment instrument. STUDY: Consenting community patients without known BE were randomly assigned to receive huTNE, muTNE, or sEGD, followed by a telephone administered preference and tolerability assessment instrument 24 hours after study procedures. Patient preference was measured by the waiting trade-off method. RESULTS: In total, 201 patients completed screening with huTNE (n=71), muTNE (n=71), or sEGD (n=59), and a telephone interview. Patients' preferences for sEGD and uTNE using the waiting trade-off method were comparable (P=0.51). Although tolerability scores were superior for sEGD (P<0.001) compared with uTNE, scores for uTNE examinations were acceptable. CONCLUSIONS: Patient preference is comparable between sEGD and uTNE for diagnostic examinations conducted in an endoscopy suite or in a mobile setting. Given acceptable tolerability, uTNE may be a viable alternative to sEGD for BE screening.

Predictors of Progression in Barrett's Esophagus with Low-Grade Dysplasia: Results from a Multicenter Prospective BE Registry.

OBJECTIVES: Low-grade dysplasia (LGD) is a risk factor for progression in Barrett's esophagus (BE). Progression estimates however vary and predictors of progression are not well established. We aimed to assess predictors of progression in a multicenter BE-LGD cohort. METHODS: All subjects with LGD (diagnosed by a GI pathologist) in a prospective BE registry were identified. Progression was defined development of HGD/EAC more than 12 months after index date of LGD diagnosis. Clinical, endoscopic factors and impact of histologic review by an independent panel of two GI pathologists were assessed as predictors of progression. Cox proportional hazard models were used to assess their association with risk of progression. RESULTS: 244 BE-LGD subjects met inclusion criteria. Their mean age was 63.2 years. 205 (84%) were males. The median follow up was 4.8 years. Fifty six patients were diagnosed with HGD/EAC in less than 12 months, while 14 progressed to HGD/EAC after 12 months, with an overall annual risk of progression of 1.2%. 29% of LGD subjects were downgraded to non-dysplastic and the remaining re-confirmed as LGD or indefinite dysplasia. The risk of progression in the reconfirmed LGD group was eight fold higher (hazards ratio: 7.6, 95% CI: 1.5-139.4) in a propensity score stratified model. CONCLUSIONS: In this large BE-LGD cohort, progression risk increased substantially when an additional panel of two expert GI pathologists re-confirmed a LGD diagnosis. These BE subjects may be candidates for endoscopic therapy. LGD was a marker of prevalent HGD/EAC in 18% of patients.

Prevalence and Predictors of Gastroesophageal Reflux Complications in Community Subjects.

BACKGROUND: Predictors of erosive esophagitis (EE) and Barrett's esophagus (BE) and the influence of number of risk factors in the community are not well defined. METHODS: Rates of BE and EE among community residents identified in a randomized screening trial were defined. The risk of EE and BE associated with single and multiple risk factors (gender, age, GERD, Caucasian ethnicity, ever tobacco use, excess alcohol use, family history of BE or EAC, and central obesity) was analyzed. RESULTS: Sixty-eight (33 %) of 205 subjects had EE and/or BE. BE prevalence was 7.8 % with dysplasia present in 1.5 %. Rates were comparable between subjects with and without GERD. Male sex and central obesity were independent risk factors. The odds of EE or BE were 3.7 times higher in subjects with three or four risk factors and 5.7 times higher in subjects with five or more risk factors compared with those with two or less factors. CONCLUSIONS: EE and BE are prevalent in the community regardless of the presence of GERD. Risk appeared to be additive, increasing substantially with three or more risk factors.

A randomized comparative effectiveness trial of novel endoscopic techniques and approaches for Barrett's esophagus screening in the community.

OBJECTIVES: The objective of this study was to compare participation rates and clinical effectiveness of sedated esophagogastroduodenoscopy (sEGD) and unsedated transnasal endoscopy (uTNE) for esophageal assessment and Barrett's esophagus (BE) screening in a population-based cohort. METHODS: This was a prospective, randomized, controlled trial in a community population. Subjects ≥50 years of age who previously completed validated gastrointestinal symptom questionnaires were randomized (stratified by age, sex, and reflux symptoms) to one of three screening techniques (either sEGD or uTNE in a mobile research van (muTNE) or uTNE in a hospital outpatient endoscopy suite (huTNE)) and invited to participate. RESULTS: Of the 459 subjects, 209 (46%) agreed to participate (muTNE n=76, huTNE n=72, and sEGD n=61). Participation rates were numerically higher in the unsedated arms of muTNE (47.5%) and huTNE (45.7%) compared with the sEGD arm (40.7%), but were not statistically different (P=0.27). Complete evaluation of the esophagus was similar using muTNE (99%), huTNE (96%), and sEGD (100%) techniques (P=0.08). Mean recovery times (min) were longer for sEGD (67.3) compared with muTNE (15.5) and huTNE (18.5) (P<0.001). Approximately 80% of uTNE subjects were willing to undergo the procedure again in future. Respectively, 29% and 7.8% of participating subjects had esophagitis and BE. CONCLUSIONS: Mobile van and clinic uTNE screening had comparable clinical effectiveness with similar participation rates and safety profile to sEGD. Evaluation time with uTNE was significantly shorter. Prevalence of BE and esophagitis in community subjects ≥50 years of age was substantial. Mobile and outpatient unsedated techniques may provide an effective alternative strategy to sEGD for esophageal assessment and BE screening.

Epidemiology and Outcomes of Young-Onset Esophageal Adenocarcinoma: An Analysis from a Population-Based Database.

BACKGROUND: Esophageal adenocarcinoma is a lethal cancer with rising incidence. There are limited data in younger (<50 years) patients with esophageal adenocarcinoma. We aimed to assess time trends in the incidence and outcomes of "young-onset" esophageal adenocarcinoma using a population-based database. METHODS: We queried the Surveillance, Epidemiology, and End Results 9 database to identify patients with esophageal adenocarcinoma between 1975 and 2015. Patients were stratified into three age strata: <50, 50 to 69, and ≥70 years. Staging was stratified as localized, regional, and distant. Trends in incidence, disease stage, and survival were assessed in three periods (1975-89, 1990-99, and 2000-2015). Univariate and multivariate models were created to identify predictors of mortality. RESULTS: Esophageal adenocarcinoma incidence has increased in patients <50 years of age, with an annual percentage change of 2.9% (95% confidence interval, 1.4%-4.4%) from 1975 to 2015. Young-onset esophageal adenocarcinoma presented at more advanced stages (regional + distant) compared with older patients (84.9% vs. 67.3%; P < 0.01), with increasing proportion of advanced stages over the study period. These patients also experienced poorer 5-year esophageal adenocarcinoma-free survival compared with older patients (22.9%% vs. 29.6%; P < 0.01), although this finding was attenuated on stage-stratified analysis. CONCLUSIONS: Young-onset esophageal adenocarcinoma, while uncommon, is rising in incidence. Concerningly, the proportion of advanced disease continues to increase. Young-onset esophageal adenocarcinoma also presents at more advanced stages, resulting in poorer esophageal adenocarcinoma-free survival. IMPACT: Patients with esophageal adenocarcinoma younger than 50 years present at more advanced stages with higher esophageal adenocarcinoma-specific mortality compared with older peers. Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated.

How Physicians Prepare for Maintenance of Certification Exams: A Qualitative Study.

PURPOSE: Little is known about how board-certified physicians prepare for their periodic maintenance of certification (MOC) examinations. This qualitative study explores how physicians experience MOC exam preparation: how they prepare for the exams and decide what to study and how exam preparation compares with what they normally do to keep their medical knowledge current. METHOD: Between September 2016 and March 2017, the authors interviewed 80 primary care physicians who had recently taken either the American Board of Family Medicine or American Board of Internal Medicine MOC exam. They analyzed transcripts and notes from these interviews looking for patterns and emergent themes, using the constant comparative method and a social practice theory perspective. RESULTS: Most interviewees studied for their MOC exams by varying from their routines for staying current with medical knowledge, both by engaging with a different scope of information and by adopting different study methods. Physicians described exam preparation as returning to a student/testing mindset, which some welcomed and others experienced negatively or with ambivalence. CONCLUSIONS: What physicians choose to study bounds what they can learn from the MOC exam process and, therefore, also bounds potential improvements to their patient care. Knowing how physicians actually prepare, and how these activities compare with what they do when not preparing for an exam, can inform debates over the value of requiring such exams, as well as conversations about how certification boards and other key stakeholders in physicians' continuing professional development could improve the MOC process.

Targeting the COX1/2-Driven thromboxane A2 pathway suppresses Barrett's esophagus and esophageal adenocarcinoma development.

BACKGROUND: Barrett's esophagus (BE), a complication of gastroesophageal reflux disease (GERD), predisposes patients to esophageal adenocarcinoma (EAC). Reliable biomarkers for early detection and discovery of potential drug targets are urgently needed for improved BE and EAC patient outcomes. METHODS: Patient biopsy samples were evaluated for COX1/2, and thromboxane A2 synthase (TBXAS) expression. Circulating prostaglandins biosynthesis was determined using enzyme immunoassay kits. Anchorage-independent cell growth assay, crystal violet staining assay, and xenograft experiments were conducted to assess BE and EAC cell growth. A surgical mouse model of reflux (i.e., esophagoduodenostomy) was established and samples were analyzed using an enzyme immunoassay kit, immunohistochemistry, immunoblotting, or RT-PCR. Esophageal biopsy samples (pre- and post-intervention) were obtained from a randomized clinical trial in which participants were administered esomeprazole (40 mg) twice daily in combination with an acetylsalicylic acid (ASA) placebo or 81 or 325 mg ASA for 28 days. Esophageal biopsy specimens before and after the intervention period were analyzed. FINDINGS: COX2 and TBXAS are highly expressed in BE and EAC patients accompanied by a pronounced elevation of circulating TXA2 levels. ASA suppressed BE and EAC growth by targeting the TXA2 pathway. Additionally, biopsies from 49 patients (with similar baseline characteristics) showed that ASA substantially decreased serum TXA2 levels, resulting in reduced inflammation. INTERPRETATION: This study establishes the importance of the COX1/2-driven TXA2 pathway in BE and EAC pathophysiology and lays the groundwork for introducing a TXA2-targeting strategy for EAC prevention and early detection. FUNDING: Hormel Foundation, Exact Sciences, Pentax Medical, Intromedic and National Cancer.

Emergency department physician activation of the catheterization laboratory and immediate transfer to an immediately available catheterization laboratory reduce door-to-balloon time in ST-elevation myocardial infarction.

BACKGROUND: Consensus guidelines and hospital quality-of-care programs recommend that ST-elevation myocardial infarction patients achieve a door-to-balloon time of < or = 90 minutes. However, there are limited prospective data on specific measures to significantly reduce door-to-balloon time. METHODS AND RESULTS: We prospectively determined the impact on median door-to-balloon time of a protocol mandating (1) emergency department physician activation of the catheterization laboratory and (2) immediate transfer of the patient to an immediately available catheterization laboratory by an in-house transfer team consisting of an emergency department nurse, a critical care unit nurse, and a chest pain unit nurse. We collected door-to-balloon time for 60 consecutive ST-elevation myocardial infarction patients undergoing emergency percutaneous intervention within 24 hours of presentation from October 1, 2004, through August 31, 2005, and compared this group with 86 consecutive ST-elevation myocardial infarction patients from September 1, 2005, through June 26, 2006, after protocol implementation. Median door-to-balloon time decreased overall (113.5 versus 75.5 minutes; P<0.0001), during regular hours (83.5 versus 64.5 minutes; P=0.005), during off-hours (123.5 versus 77.5 minutes; P<0.0001), and with transfer from an outside affiliated emergency department (147 versus 85 minutes; P=0.0006). Treatment within 90 minutes increased from 28% to 71% (P<0.0001). Mean infarct size decreased (peak creatinine kinase, 2623+/-3329 versus 1517+/-1556 IU/L; P=0.0089), as did hospital length of stay (5+/-7 versus 3+/-2 days; P=0.0097) and total hospital costs per admission ($26,826+/-29,497 versus $18,280+/-8943; P=0.0125). CONCLUSIONS: Emergency department physician activation of the catheterization laboratory and immediate transfer of the patient to an immediately available catheterization laboratory reduce door-to-balloon time, leading to a reduction in myocardial infarct size, hospital length of stay, and total hospital costs.

Comparative quality assessment of esophageal examination with transnasal and sedated endoscopy.

Background Unsedated transnasal esophagoscopy (TNE) may offer a less expensive, mobile alternative to sedated esophagogastroduodenoscopy (EGD) for evaluations of reflux related complications. Comparisons of imaging quality by these methods are lacking. Methods Two reviewers evaluated videos of TNE and EGD procedures, performed during a community randomized study comparing endoscopic techniques. Subjects were randomized to EGD, TNE in endoscopy suite, or TNE in mobile research unit. Endoscopic quality was assessed using a validated scoring tool. Results In total, 115 videos (58 EGD, 28 endoscopy suite TNE, and 29 mobile TNE) were reviewed. Overall quality scores for TNE and EGD were excellent without a statistically significant difference (P = 0.30). There were no differences in gastroesophageal junction (GEJ) visualization scores, though EGD scored higher in esophageal passage (P < 0.05) and TNE scored higher in esophageal intubation (P < 0.05). There was no significant difference in any quality score between mobile TNE and gastrointestinal suite TNE. Conclusion Esophageal assessment with TNE or EGD was comparable in overall quality and GEJ visualization. TNE quality was not affected by procedure location. TNE is a feasible option for endoscopic assessment of reflux complications.

Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium.

BACKGROUND: While central obesity increases gastroesophageal reflux (GER) by mechanically disrupting the anti-reflux barrier, limited data exist on pathways by which central obesity may potentiate esophageal injury by non-mechanical means. Obesity has been associated with an impaired epithelial intestinal barrier. OBJECTIVE: We aimed to assess the influence of central obesity and reflux on the squamous esophageal epithelial intercellular space diameter (ICSD). METHODS: The ICSD was measured using electron microscopy in esophageal biopsies from individuals who underwent ambulatory pH monitoring and endoscopy. Anthropometric measurements were obtained on all participants. Participants were classified into four groups: with and without central obesity and reflux. RESULTS: Sixteen individuals were studied with four in each study group. The mean ICSD was almost three-fold greater (p < 0.001) in the group with central obesity without reflux, compared to controls without central obesity and reflux. It was also comparable to the ICSD in groups with acid reflux only and those with both reflux and central obesity. CONCLUSIONS: There is evidence of esophageal squamous ICSD increase in individuals with central obesity who do not have evidence of acid and nonacid reflux on ambulatory pH monitoring. This may reflect a mechanism by which central obesity potentiates reflux-induced esophageal injury and inflammation.