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Background and Study Aims: Methylene blue selectively stains specialized columnar epithelium in Barrett's esophagus with high accuracy. We prospectively evaluated the methylene blue staining properties of dysplastic and nondysplastic Barrett's esophagus and the association of these properties with the risk for dysplasia and cancer., Patients and Methods: In a ex vivo study, we mapped, photographed, and sampled esophagectomy specimens with high grade dysplasia and/or early adenocarcinoma before and after methylene blue staining. In a concurrent in vivo study, we performed methylene blue staining and characterized methylene blue stain characteristics. Pathologists estimated the proportion of specialized columnar epithelium in each specimen and graded dysplasia., Results: We examined 551 biopsies from 47 patients with biopsy-proven Barrett's esophagus and 48 sections from five surgical specimens with Barrett's esophagus and dysplasia and early adenocarcinoma. The accuracy of ex vivo and in vivo methylene blue staining for specialized columnar epithelium was 87% and 90%, respectively. It was influenced by the length of Barrett's esophagus, biopsy location, and the presence of esophagitis and/or dysplasia. Light to absent staining (p = 0.01) and moderate to marked heterogeneity (p = 0.01) were significantly associated with high grade dysplasia or cancer in the univariate analysis and in a multivariate model that adjusted for the length of Barrett's esophagus and the presence of a lesion. These staining characteristics were present in all patients with severe dysplasia and/or adenocarcinoma., Conclusions: Highly dysplastic or malignant Barrett's esophagus stains differently with methylene blue. Increased heterogeneity and decreased methylene blue stain intensity are significant independent predictors of high grade dysplasia and/or cancer. These features may help to direct biopsies in patients without a lesion.

Objective: The reported risk of progression from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or carcinoma (CA) in Barrett's esophagus varies. However, the validity of a diagnosis of LGD may be questioned because of interobserver variability., Methods: A search of the Cleveland Clinic Foundation surgical pathology files between 1986 and 1997 yielded biopsy specimens from 43 patients with Barrett's esophagus diagnosed and coded as LGD. Patients with concurrent or prior diagnoses of HGD or carcinoma were excluded. The LGD cases were randomized and blindly reviewed by three gastrointestinal (GI) pathologists along with cases originally diagnosed as Barrett's esophagus without dysplasia (ND; n = 28), indefinite for dysplasia (IND; n = 14), or HGD (n = 15). Each pathologist classified every biopsy specimen as ND, IND, LGD, or HGD, and interobserver agreements were determined by kappa statistics (K). Follow-up data were available on 25 patients originally diagnosed with LGD. Progression was defined as a subsequent diagnosis of HGD or CA on esophageal biopsy or resection specimens., Results: Agreement between two GI pathologists for a diagnosis of LGD was fair (K = 0.28) and poor (K = 0.21 and -0.04). Individual GI pathologists agreed with the original diagnosis of LGD in 70%, 56%, and 16% of cases. The 25 patients with follow-up included 21 men and four women (mean age, 67 yr) with a mean follow-up of 26 months (range: 2-84 months). Seven patients (28%) with follow-up developed HGD (five patients) or CA (two patients), 2-43 months (median: 11 months) after a diagnosis of LGD. The individual GI pathologists' diagnosis did not correlate with progression. However, when at least two GI pathologists agreed on LGD, there was a significant association with progression (seven of 17 patients, 41%, p = 0.04). When all three GI pathologists agreed on a diagnosis of LGD, four of five patients progressed (p = 0.012). In contrast, of the eight patients with follow-up and no agreement among GI pathologists for a diagnosis of LGD, none progressed., Conclusions: A high degree of interobserver variability is seen in the histological diagnosis of Barrett's esophagus-related LGD. Although the number of observations is low, a consensus diagnosis of LGD among GI pathologists suggests an increased risk of progression from LGD to HGD or carcinoma.

Background: Endoscopically applied methylene blue selectively stains specialized columnar epithelium in Barrett's esophagus., Methods: The diagnostic yield and cost of cancer surveillance in patients with Barrett's esophagus using methylene blue-directed biopsies (MBDB) were compared with surveillance using a "jumbo" random biopsy technique in a prospective, sequential, controlled trial. Esophagogastroduodenoscopy was performed with either MBDB or random biopsy in a randomized sequence. The proportions of various types of epithelia in each biopsy were estimated and dysplasia was graded in a blinded fashion., Results: Forty-three patients with short- (n = 8), limited- (n = 10), and long-segment (n = 25) Barrett's esophagus were studied. Using MBDB technique, the average number of biopsies obtained per patient was significantly lower and the proportion of specialized columnar epithelium in each specimen was significantly higher compared with random biopsy. Dysplasia or cancer was diagnosed in significantly more MBDB specimens (12% vs. 6%, p = 0.004). Despite fewer biopsies per patient using MBDB, dysplasia or cancer was diagnosed in significantly more patients (44% vs. 28%, p = 0.03) than by random biopsy technique. MBDB cost less and detected more cancers than random biopsy., Conclusions: MBDB is a more accurate and cost-effective technique than random biopsy for diagnosing specialized columnar epithelium and dysplasia/cancer, particularly in long-segment Barrett's esophagus.

Background & Aims: A less costly cancer surveillance method for Barrett's esophagus is desirable. The aim of this study was to compare nonendoscopic balloon cytology with biopsy and brush cytology for detecting dysplasia and carcinoma in patients with Barrett's esophagus., Methods: Patients in a surveillance program underwent balloon cytology before endoscopy with biopsy and brush cytology. Results of cytology were compared with those of histology., Results: Adequate columnar epithelium was obtained in 52 of 63 (83%) patients with balloon cytology and 59 of 61 (97%) with brush cytology. Balloon cytology obtained abnormal cells in 6 of 8 patients with adenocarcinoma, 2 of 2 patients with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia. Sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% but only 25% for low-grade dysplasia. No patients without dysplasia or carcinoma had abnormal cells. Brush cytology was abnormal in all 11 patients with high-grade dysplasia or carcinoma but only 2 of 9 patients with low-grade dysplasia (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells (specificity, 95%). Balloon cytology cost was sixfold less than endoscopy with biopsy., Conclusions: Balloon cytology detected 80% of patients with high-grade dysplasia or carcinoma when sampling was adequate. Brush cytology data suggest that a more abrasive balloon may improve balloon cytology sensitivity. The potential cost savings of balloon cytology compared with endoscopic cancer surveillance in Barrett's esophagus support further studies of this technique.

Background: Specialized columnar epithelium in Barrett's esophagus resembles gastric intestinal metaplasia, which selectively stains with methylene blue., Methods: We prospectively evaluated the safety, accuracy, reproducibility, cost, and diagnostic yield of methylene blue-directed biopsy in detecting specialized columnar epithelium and dysplasia in Barrett's esophagus. We performed upper endoscopy with methylene blue-directed biopsy and obtained 236 large cup biopsy specimens (145 stained, 91 unstained) from 14 patients with Barrett's esophagus of any length (Group 1) and 12 control patients. Biopsy specimens were independently examined by two pathologists unaware of the endoscopic results., Results: Methylene blue stained specialized columnar epithelium in 18 of the 26 patients, including those with intramucosal carcinoma (1), high-grade dysplasia (1), and indefinite/low-grade dysplasia (6). Methylene blue staining pattern, which was focal in 72% and diffuse in 28% of patients, was reproduced in 8 patients who had repeat staining within 4 weeks. The overall accuracy of methylene blue staining for detecting specialized columnar epithelium was 95%. The diagnostic yield of methylene blue staining for specialized columnar epithelium in "control" patients was 42%. The risk for dysplasia in stained biopsy specimens was greater than in unstained ones (odds ratio 17.7, p = .0004)., Conclusions: Methylene blue mucosal staining is a safe, inexpensive, reproducible, and highly accurate method of diagnosing specialized columnar epithelium in Barrett's esophagus.

The role of surgery in patients with Barrett's esophagus and high-grade dysplasia is controversial. The aims of this study were to determine the prevalence of unsuspected early cancer and to evaluate surgical outcome in a cohort of patients with high-grade dysplasia. Records of all 16 patients who underwent esophagectomy for high-grade dysplasia from 1986 to 1991 were reviewed. All had preoperative endoscopy with no gross evidence of carcinoma, and none had a preoperative diagnosis of intramucosal or invasive carcinoma. Intramucosal carcinoma was found in six (38%) resection specimens. There were no cases of invasive carcinoma or lymph node metastases. One patient (6%) died 3 months postoperatively. The remaining patients are alive without evidence of recurrent cancer (range of follow-up, 2-68 months). Early postoperative complications occurred in seven patients (44%). Late complications occurred in 11 patients (73%). Anastomotic strictures accounted for seven of the 11 (64%) late complications. Complications were successfully managed conservatively in all but two patients. One required laryngectomy for chronic aspiration and another required a gastrojejunostomy for gastric outlet obstruction. Intramucosal carcinoma that had been unsuspected is frequently found in patients with Barrett's esophagus and high-grade dysplasia. Mortality associated with esophagectomy is low, and perioperative complications can usually be managed conservatively. Esophageal resection is indicated in appropriately selected patients with Barrett's esophagus and high-grade dysplasia.