Distribution of body fat and its influence on esophageal inflammation and dysplasia in patients with Barrett's esophagus.

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

Safety of prior endoscopic mucosal resection in patients receiving radiofrequency ablation of Barrett's esophagus.

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

High-grade dysplasia and intramucosal adenocarcinoma in Barrett's esophagus: the role of endoscopic eradication therapy.

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

History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus.

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

Endoscopic tri-modal imaging is more effective than standard endoscopy in identifying early-stage neoplasia in Barrett's esophagus.

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

Prevalence of esophageal eosinophils in patients with Barrett's esophagus.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.

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

Outcomes of T1b esophageal adenocarcinoma patients.

BACKGROUND: Esophagectomy is usually recommended for patients with submucosal esophageal adenocarcinoma (T1b EAC) because of the potential for lymph node metastasis (LNM). Endoscopic management often differs based on the risk of metastasis. There is limited information on the difference in outcomes for T1b-EAC with and without esophagectomy. OBJECTIVES: To investigate (1) the outcomes of T1b EAC treatments with and without esophagectomy and (2) the percentage of LNM at esophagectomy for T1b-EAC. DESIGN: Retrospective cohort. SETTING: A tertiary Barrett's esophagus unit. PATIENTS: Sixty-eight T1b EAC patients based on EMR histology. INTERVENTIONS: Esophagectomy and endoscopic therapies. MAIN OUTCOME MEASUREMENTS: Survival duration and mortality rate. RESULTS: A total of 68 patients had T1b EAC; cumulative mortality rate was 30.9% and median survival duration was 39.5 months. Thirty-nine underwent esophagectomy and 29 did not. Among patients who underwent esophagectomy, 13 (33.3%) had LNM, and the mortality rate was 50.0% and 11.1% for those with and without LNM, respectively (P < .01). For those with and without esophagectomy, the cumulative mortality rates were 25.6% and 37.9%, and median survival duration was 48.9 and 34.8 months, respectively. There was no statistical difference in Charlson comorbidity index, number of EMRs, mortality rate, or survival duration. In Cox proportional hazard model analysis, the hazard ratio for esophagectomy was 0.5 (P = .21). LIMITATIONS: Retrospective, nonrandomized small sample size cohort. CONCLUSION: Among the patients with T1b EAC found in EMR specimens who underwent esophagectomy, one third had regional LNM. In our small series, patients who underwent esophagectomy did not have a significantly different survival duration from that of those who did not, indicating that these patients may have similar outcomes [corrected].

Endoscopic mucosal resection in the management of esophageal neoplasia: current status and future directions.

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

Depth of submucosal invasion does not predict lymph node metastasis and survival of patients with esophageal carcinoma.

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