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Background & Aims: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations., Methods: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls., Results: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9))., Conclusions: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE) and to provide end points for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patient assessments of disease severity. We also evaluated relationships between patient assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings., Methods: We collected information from 186 patients with EoE in Switzerland and the United States (69.4% male; median age, 43 y) via surveys (n = 135), focus groups (n = 27), and semistructured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patient assessment of EoE severity. The PRO instrument was used prospectively in 153 adult patients with EoE (72.5% male; median age, 38 y), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 y)., Results: Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patient assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity (range, 0-10) and PRO score (range, 0-8.52) was 0.15., Conclusions: We developed and validated an EoE scoring system based on 7 PRO items that assess symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). However, the relationships may be affected by bias and confounding., Methods: We used data from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided., Results: The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses., Conclusions: People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Unlabelled: BACKGROUND& AIMS: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E(2) in patients with BE with no dysplasia or low-grade dysplasia., Methods: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE(2) (the primary end point)., Results: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE(2) was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P = .02 vs arm A)., Conclusions: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE(2) in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Background & Aims: Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA., Methods: We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement., Results: Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated., Conclusions: We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Minimally invasive esophagectomy (MIE) has been performed using a variety of techniques evolving during the past decade. We present our initial experience and outcomes of patients undergoing transthoracic MIE using a circular end-to-side anastomosis created with the transorally directed EEA circular stapler OrVil (Covidien, New Haven, CT). Complications, including anastomotic leak and stricture occurrence, are reviewed., Methods: A retrospective review evaluated consecutive patients undergoing MIE for esophageal cancer or related disease with intrathoracic end-to-side anastomoses using the transorally directed EEA circular stapler from December 2007 to May 2010. Medical records were reviewed for demographics, staging, neoadjuvant chemoradiotherapy, comorbidities, adjuvant therapy, complications, and survival., Results: During this period, 51 consecutive patients (84% male; mean age, 65 years) underwent MIE. Neoadjuvant chemoradiotherapy was performed in 32 patients, and 4 had intraoperative radiotherapy. Mean operative time was 338 minutes (range, 211 to 565 minutes), including the 4 patients with intraoperative radiotherapy. Operative time improved with experience (excluding intraoperative radiotherapy) from a mean of 378 minutes (patients 1 to 14) to 300 minutes (patients 37 to 51). Median hospital stay was 11 days (range, 6 to 48 days). Anastomotic leaks occurred in 5 patients (9.8%). Postoperative deaths included 1 in-hospital (2.0%) and 2 (3.9%) after discharge. Stricture was diagnosed and treated in 7 patients (13.7%). Follow-up was a median of 12 months (range, 1 to 31 months)., Conclusions: Transthoracic MIE using an end-to-side anastomosis with the transorally directed EEA circular stapler resulted in acceptable stricture and leak rates with good outcomes comparable to published outcomes for open surgical resections., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Upper abdominal pain (UAP) in patients with gallstones is often treated by cholecystectomy but it frequently persists. We aimed to identify symptoms associated with relief., Methods: We followed 1008 patients who received cholecystectomy for gallstones and UAP at the Mayo Clinic (Rochester, Minnesota) or Kaiser Permanente (San Diego, California) for 12 months. A validated, self-completed biliary symptoms questionnaire identified features of UAP, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS); the questionnaire was given initially and 3 and 12 months after cholecystectomy, to identify features that predicted sustained relief of UAP., Results: Five hundred ninety-four patients (59%) reported relief from UAP. Factors associated univariately (P < .05) with relief included frequency of UAP ≤1 per month, onset ≤1 year preoperatively, usual duration (30 minutes to 24 hours, most often in the evening or night), and severity >5/10. Compared to no features, multiple predictive features of UAP (frequency, onset, duration, or timing) were associated with increasing odds ratios (95% confidence interval) for relief: 1, 2, or 3 features (4.2 [1.1-16]; P = .03) and 4 features (6.3 [1.6-25]; P = .008). Negative univariate associations included lower abdominal pain (LAP), usual bowel pattern, nausea ≥1 per week, often feeling bloated or burpy, GERD, and/or IBS. There was an inverse association between relief and somatization; relief was not associated with postprandial UAP. Multivariable logistic regression analysis revealed independent associations (P < .05) with UAP frequency, onset, and nocturnal awakening, but inverse associations with lower abdominal pain, abnormal bowel pattern, and frequent bloated or burpy feelings., Conclusions: UAP features and concomitant GERD, IBS, and somatization determine the odds for relief from UAP after cholecystectomy., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. In 2007, a consensus recommendation provided clinical and histopathologic guidance for the diagnosis and treatment of EoE; however, only a minority of physicians use the 2007 guidelines, which require fulfillment of both histologic and clinical features. Since 2007, the number of EoE publications has doubled, providing new disease insight. Accordingly, a panel of 33 physicians with expertise in pediatric and adult allergy/immunology, gastroenterology, and pathology conducted a systematic review of the EoE literature (since September 2006) using electronic databases. Based on the literature review and expertise of the panel, information and recommendations were provided in each of the following areas of EoE: diagnostics, genetics, allergy testing, therapeutics, and disease complications. Because accumulating animal and human data have provided evidence that EoE appears to be an antigen-driven immunologic process that involves multiple pathogenic pathways, a new conceptual definition is proposed highlighting that EoE represents a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. The diagnostic guidelines continue to define EoE as an isolated chronic disorder of the esophagus diagnosed by the need of both clinical and pathologic features. Patients commonly have high rates of concurrent allergic diatheses, especially food sensitization, compared with the general population. Proved therapeutic options include chronic dietary elimination, topical corticosteroids, and esophageal dilation. Important additions since 2007 include genetic underpinnings that implicate EoE susceptibility caused by polymorphisms in the thymic stromal lymphopoietin protein gene and the description of a new potential disease phenotype, proton pump inhibitor-responsive esophageal eosinophila. Further advances and controversies regarding diagnostic methods, surrogate disease markers, allergy testing, and treatment approaches are discussed., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Several small series have suggested an increased risk of complications associated with esophageal dilation in patients with eosinophilic esophagitis (EoE)., Objective: To quantitate the risk and identify risk factors for esophageal complications in dilation in EoE patients., Design: Retrospective, uncontrolled, single-center study., Setting: Tertiary referral hospital., Patients: A total of 161 EoE patients (mean ± standard deviation age 44.3 ± 15.3 years, 112 men, 49 women, 150 white patients, 10 unknown, 1 Asian)., Interventions: Through-the-scope balloon or Savary dilation of EoE., Main Outcome Measurements: The rate of complications defined as deep mucosal tear, major bleeding, or perforation, and determination of risk factors for complications., Results: A total of 293 dilations were performed in 161 patients. Complications reported were deep mucosal tear in 9.2% (n = 27), major bleeding in 0.3% (n = 1), and immediate perforation in 1.0% (n = 3). All patients with perforations were successfully treated medically without surgery (mean ± standard deviation hospital stay 5.3 ± 3.2 days). Factors associated with an increased risk of complications were luminal narrowing in the upper (odds ratio [OR], 5.62; 95% CI, 2.07-15.26; P < .001) and middle third of the esophagus (OR, 4.93; 95% CI, 1.64-14.83; P < .005) compared with lower third, luminal stricture unable to be traversed with a standard upper endoscope (OR, 2.48; 95% CI, 1.06-5.83; P = .037), and use of Savary dilator (OR, 2.63; 95% CI, 1.18-5.83; P = .018)., Limitations: Retrospective design, uncontrolled study., Conclusions: Deep mucosal tears are common after dilation (9%), but the risk of immediate transluminal perforation with EoE is approximately 1%. The risk of severe complications is increased in patients with more proximal stricture and strictures that initially prevent endoscope passage., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

The aim of this study was to develop the Mayo Dysphagia Questionnaire-30 Day (MDQ-30), a tool to measure esophageal dysphagia, by adapting items from validated instruments for use in clinical trials, and assess its feasibility, reproducibility, and concurrent validity. Outpatients referred to endoscopy for dysphagia or seen in a specialty clinic were recruited. Feasibility testing was done to identify problematic items. Reproducibility was measured by test-retest format. Concurrent validity reflects agreement between information gathered in a structured interview versus the patients' written responses. The MDQ-30, a 28-item instrument, took 10 min (range = 5-30 min) to complete. Four hundred thirty-one outpatients [210 (49%) men; mean age = 61 years] participated. Overall, most concurrent validity kappa values for dysphagia were very good to excellent with a median of 0.78 (min 0.28, max 0.95). The majority of reproducibility kappa values for dysphagia were moderate to excellent with a median kappa value of 0.66 (min 0.07, max 1.0). Overall, concurrent validity and reproducibility kappa values for gastroesophageal reflux disease (GERD) symptoms were 0.81 (95% CI = 0.72, 0.91) and 0.66 (95% CI = 0.55, 0.77), respectively. Individual item percent agreement was generally very good to excellent. Internal consistency was excellent. We conclude that the MDQ-30 is an easy-to-complete tool to evaluate reliably dysphagia symptoms over the last 30 days.

Background & Aims: Lichen planus is a relatively uncommon, presumed autoimmune disease that affects middle-aged patients and is manifested in the skin, nails, and mucous membranes. Reports of esophageal involvement have been rare, despite the classification of the esophagus as a mucous membrane., Methods: Assuming esophageal involvement might not be as rare as expected, we reviewed the Mayo Clinic Pathology Database for all cases from 2000 to the present., Results: Twenty-seven cases were identified, with a mean age of 64 years; 25 were women. Patients presenting with esophageal lichen planus as the initial manifestation and those with a diagnosis of lichen planus involving other sites were equal in number. Many patients had received multiple dilations and reflux treatments before diagnosis. All patients presented with dysphagia. Endoscopy and radiology studies demonstrated a wide range of abnormalities, including strictures of varying length and location, small-caliber esophagus, and a mucosal appearance of sloughing, white discoloration, erythema, thickening, and superficial ulceration. Treatment regimens varied markedly, with some patients responding to topical or systemic corticosteroids., Conclusions: Esophageal lichen planus is rare but probably more common than previously suspected. It presents with a wide range of endoscopic signs and is commonly the presenting sign of lichen planus. In evaluating middle-aged patients with strictures, particularly proximal esophageal strictures in women, physicians should consider a diagnosis of lichen planus even in the absence of extraesophageal manifestations., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The incidence of esophageal adenocarcinoma (EAC) has increased dramatically in the western world, and there also appears to have been an increase in the incidence of Barrett's esophagus and gastroesophageal reflux disease in recent years. The contemporaneous increase in obesity has focused interest on whether obesity is a risk factor for EAC and its precursors. This article reviews current evidence for the role that overweight/obesity and body fat distribution have in development of the esophagitis metaplasia-dysplasia-adenocarcinoma sequence. Particular attention is paid to the stage at which adiposity may act to influence the risk of EAC, because this determines the importance of weight control and weight loss at each stage in the disease spectrum for the prevention of EAC.

The effort to improve outcomes in esophageal cancer has included attempts at improving staging and patient selection. 2-Deoxy-2-[(18)F]fluoro-Dglucose positron emission tomography (FDG-PET) has been extensively studied in this context and has been widely accepted as a staging tool. Its role in restaging or assessing therapeutic response is investigational and promising. Laparoscopy has also been studied as a means for improving staging, but its role may be limited in the era of PET. This article discusses the literature assessing these modalities, particularly with regard to the practical management of the patient in the clinic.

Background & Aims: Guidelines for reporting Barrett's esophagus and hiatal hernia measurements and reflux esophagitis grades have been developed to improve consistency, communication, and, ultimately, patient care. Our aims were to assess the percentage of cases in which findings were reported in accordance with guidelines and to assess the impact of education and feedback on reporting behavior., Methods: Prospective cross-sectional study design was used. Chart reviews were performed for all adult patients who underwent esophagogastroduodenoscopy at a tertiary care center during three 2-month time periods during a 12-month interval: Time 1 (March 1, 2004-April 30, 2004), Time 2 (July 1, 2004-August 31, 2004), and Time 3 (March 1, 2005-April 30, 2005). Standardized educational sessions began 2 years before Time 1. No intervention took place between Time 1 and Time 2; data were collected to examine secular change. Between Time 2 and Time 3, individual and group feedback and refresher sessions were given., Results: Five thousand six hundred nine eligible esophagogastroduodenoscopies were performed, of which 2675 demonstrated Barrett's esophagus, hiatal hernia, and/or reflux esophagitis. At baseline, Barrett's esophagus and hiatal hernia measurements were dictated correctly in a median of 67% and 86% of cases, respectively, improving to 100% (P < .05) and 98% (P < .01) of cases, respectively. The Los Angeles Classification system was used in a median of 100% of cases at baseline and at follow-up., Conclusions: Anonymous individual and group feedback, in combination with brief, structured didactic educational sessions, significantly improves compliance with established guidelines for the reporting of Barrett's esophagus and hiatal hernia. Once successfully incorporated into clinical practice, adherence to the esophagitis Los Angeles Classification System is easy to maintain.

Objective: To develop and validate a questionnaire for supraesophageal manifestations of reflux (SER) that will facilitate its study in clinical and research settings., Study Design: The Supraesophageal Reflux Questionnaire (SERQ) and previously validated Reflux Symptom Index (RSI) were subjected to multiple types of validity testing, including content validity, concurrent validity, reproducibility, and predictive validity., Results: The concurrent validity and reproducibility of both instruments was good to excellent for most items tested. The predictive validity of the SERQ was superior to the RSI when it included the covariates of history of sinusitis, use of over-the-counter antacid medications, age, gender, and body mass index., Conclusions: The SERQ will serve as both a useful clinical and research tool by offering not only SER symptom information, like the RSI, but also information about the patient's medical history and medication usage that will facilitate use of the SERQ in research protocols., Ebm Rating: B-2b.

Hypermethylation of secreted frizzled-related proteins (SFRP) genes frequently occurs with several cancers but has not been studied in esophageal adenocarcinoma or its precursor-Barrett's esophagus. To explore the role of SFRP methylation in the neoplastic progression of Barrett's esophagus and to evaluate methylated SFRP genes as biomarkers for Barrett's esophagus and cancer, methylation of SFRP genes was determined in esophageal adenocarcinomas, Barrett's esophagus and normal epithelia using methylation-specific PCR. Protein expression of SFRP genes was then assessed in these tissues by immunohistochemistry. The mRNA expression of SFRP genes was quantified by real-time reverse-transcription PCR in esophageal adenocarcinoma cell lines with and without demethylation by 5-aza-2'deoxycytidine and inhibition of deacetylation by trichostatin A treatment. Hypermethylation of SFRP1, 2, 4 and 5 was detected in 93%, 83%, 73% and 85% of 40 cancers; 81%, 89%, 78% and 73% of 37 Barrett's epithelia; 25%, 64%, 32% and 21% of 28 adjacent normal epithelia from Barrett's patients; and 10%, 67%, 0% and 13% of 30 normal esophagogastric epithelia from healthy individuals, respectively (p < 0.001 for SFRP1, 4 and 5; p < 0.05 for SFRP2). Protein expression of SFRP1, 2 and 4 was downregulated in 87%, 67% and 90% of cancers, and expression correlated inversely with grade and stage of cancers and with grade of dysplasia. Expression of SFRP2 and SFRP4 proteins was lower in cancers with corresponding gene methylation (p < 0.05). Demethylation treatment effectively re-expressed SFRP mRNA in cancer cell lines. Thus, hypermethylation of SFRP genes is a common early event in the evolution of esophageal adenocarcinoma, and methylation of SFRP1, 4 and 5 might serve as biomarkers for Barrett's neoplasia. Aberrant promoter methylation appears to functionally silence SFRP gene expression in esophageal adenocarcinoma., ((c) 2005 Wiley-Liss, Inc.)

Background & Aims: Therapy of esophageal carcinoma is stage dependent. The role of EUS-guided fine-needle aspiration (EUS FNA) in this setting is unclear. The aims of this study were to compare the performance characteristics of CT, EUS, and EUS FNA for preoperative nodal staging of esophageal carcinoma and to measure the impact of each staging test on treatment decisions., Methods: From December 1999 to March 2001, all patients with esophageal carcinoma seen at the Mayo Clinic Rochester were prospectively evaluated with CT, EUS, and EUS FNA. The impact of tumor stage on final therapy was assessed., Results: A total of 125 patients with esophageal carcinoma were enrolled. EUS FNA was more sensitive (83% vs. 29%; P < 0.001) than CT and more accurate than CT (87% vs. 51%; P < 0.001) or EUS (87% vs. 74%; P = 0.012) for nodal staging. Direct surgical resection was contraindicated in 77% of patients evaluated due to advanced locoregional/metastatic disease. Tumor location, patient age, comorbidities, and tumor stage determined by CT, EUS, and EUS FNA were associated with treatment decisions (P < 0.05). EUS FNA resulting in a higher/worse stage than CT (41 patients) was associated with a greater rate of treatments that were not direct surgeries compared with cases in which the stage was the same or better., Conclusions: EUS FNA is more accurate for nodal staging and impacts on therapy of patients with esophageal carcinoma. EUS FNA should be included in the preoperative staging algorithm of these patients.

Objectives: Gallstone disease is common and causes high health care costs, but a measure of symptomatic biliary disease for outcome studies is lacking. We aimed to develop a reproducible, valid, discriminative, disease-specific measure of biliary symptoms., Methods: We created the self-report Biliary Symptoms Questionnaire (BSQ) by combining possible biliary symptoms with validated items for gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and other disorders. We developed the final version through an iterative process and assessed reproducibility by the test-retest method, concurrent validity by comparing BSQ responses with symptoms obtained by structured interview, and discriminative validity by comparing BSQ-based diagnoses of biliary symptoms, GERD, and IBS with patients' final diagnoses. A shortened version (sBSQ) also underwent reproducibility testing., Results: A total of 245 outpatients (mean age, 55.2 yr; 61% female) participated. Median completion times for the BSQ and sBSQ were 36 and 10 min, respectively. For the BSQ, median kappa values were 0.65 (range -0.03 to 0.95) for reproducibility and 0.61 (range 0.15-0.95) for concurrent validity. Using BSQ responses, investigators distinguished IBS and GERD 79-90% of the time. For the sBSQ, the median kappa value for reproducibility was 0.72 (range 0.32-0.86)., Conclusions: The BSQ is reproducible and has good concurrent and discriminative validity for biliary symptoms. The abridged sBSQ has good reproducibility. These instruments may be useful in future outcome studies.

Objectives: Relatives of patients with Barrett's esophagus have an increased prevalence of reflux symptoms. Our aim was to find if these relatives were at increased risk of having Barrett's esophagus., Methods: First degree relatives of patients with Barrett's esophagus completed the Reflux Symptom Questionnaire. Relatives with reflux symptoms, never previously investigated. were invited for endoscopy. Controls were patients with similar reflux symptoms and no family histories of Barrett's esophagus., Results: We found previously undiagnosed Barrett's esophagus (>3 cm) in eight of 100 relatives (8%) from 53 families and in five of 100 controls (5%) (adjusted OR = 1.58, 95% CI = 0.46-5.45). Including another 27 previously investigated cases, 10 of the 53 families had two or more cases of Barrett's esophagus. Barrett's esophagus prevalence increased with age (p = 0.014) and was associated with reflux symptoms of >10 yr (p = 0.020), and Barrett's esophagus was twice as common in males (p = 0.28). Reflux esophagitis was found in 74% of relatives and 57% of controls without Barrett's (p = 0.04)., Conclusions: The risk of Barrett's esophagus in any one symptomatic relative of a patient with Barrett's esophagus was not statistically higher than in other persons with reflux symptoms. However, more relatives of Barrett's esophagus patients have reflux symptoms, so the overall prevalence of Barrett's esophagus and reflux esophagitis in relatives may also be greater than in the general population. In considering whether to screen patients with reflux symptoms for Barrett's esophagus, age and duration of symptoms are stronger predictors than having a relative with Barrett's esophagus.